Method for manufacturing a rotor having superconducting coils

DOEpatents

Driscoll, David I.; Shoykhet, Boris A.

2001-01-01

A method and apparatus for manufacturing a rotor for use with a rotating machine is provided that employs a superconducting coil on the rotor. An adhesive is applied to an outer surface of the rotor body, which may include a groove disposed within an outer surface of the rotor body. A superconducting coil is then mounted onto the rotor body such that the adhesive bonds the superconducting coil to the rotor body.

MAST magnetic diagnostics

NASA Astrophysics Data System (ADS)

Edlington, T.; Martin, R.; Pinfold, T.

2001-01-01

The mega-ampere spherical tokamak (MAST) experiment is a new, large, low aspect ratio device (R=0.7-0.8 m, a=0.5-0.65 m, maximum BT˜0.63 T at R=0.7 m) operating its first experimental physics campaign. Designed to study a wide variety of plasma shapes with up to 2 MA of plasma current with an aspect ratio down to 1.3, the poloidal field (PF) coils used for plasma formation, equilibrium and shaping are inside the main vacuum vessel. For plasma control and to investigate a wide range of plasma phenomena, an extensive set of magnetic diagnostics have been installed inside the vacuum vessel. More than 600 vacuum compatible, bakeable diagnostic coils are configured in a number of discrete arrays close to the plasma edge with about half the coils installed behind the graphite armour tiles covering the center column. The coil arrays measure the toroidal and poloidal variation in the equilibrium field and its high frequency fluctuating components. Internal coils also measure currents in the PF coils, plasma current, stored energy and induced currents in the mechanical support structures of the coils and graphite armour tiles. The latter measurements are particularly important when halo currents are induced following a plasma termination, for example, when the plasma becomes vertically unstable. The article describes the MAST magnetic diagnostic coil set and their calibration. The way in which coil signals are used to control the plasma equilibrium is described and data from the first MAST experimental campaign presented. These coil data are used as input to the code EFIT [L. Lao et al., Nucl. Fusion 25, 1611 (1985)], for measurement of halo currents in the vacuum vessel structure and for measurements of the structure of magnetic field fluctuations near the plasma edge.

Preliminary results of Malaysian nuclear agency plasma focus (MNA-PF) as a slow focus mode device for argon and deuterium filling gas in correlation with Lee model code

NASA Astrophysics Data System (ADS)

Zin, M. F. M.; Baijan, A. H.; Damideh, V.; Hashim, S. A.; Sabri, R. M.

2017-03-01

In this work, preliminary results of MNA-PF device as a Slow Focus Mode device are presented. Four different kinds of Rogowski Coils which have been designed and constructed for dI/dt signals measurements show that response frequency of Rogowski Coil can affect signal time resolution and delay which can change the discharge circuit inductance. Experimental results for 10 to 20 mbar Deuterium and 0.5 mbar to 6 mbar Argon which are captured by 630 MHz Rogowski coil in correlation with Lee Model Code are presented. Proper current fitting using Lee Model Code shows that the speed factor for MNA-PF device working with 13 mbar Deuterium is 30 kA/cm.torr1/2 at 14 kV which indicates that the device is operating at slow focus mode. Model parameters fm and fmr predicted by Lee Model Code during current fitting for 13 mbar Deuterium at 14kV were 0.025 and 0.31 respectively. Microspec-4 Neutron Detector was used to obtain the dose rate which was found to be maximum at 4.78 uSv/hr and also the maximum neutron yield calculated from Lee Model Code is 7.5E+03 neutron per shot.

Initial design of 12S-10P outer-rotor field excitation flux switching motor with different rotor width

NASA Astrophysics Data System (ADS)

Othman, Syed Muhammad Naufal bin Syed; Sulaiman, Erwan bin; Husin, Zhafir Aizat; Khan, Faisal; Mazlan, Mohamed Mubin Aizat

2015-05-01

This paper proposes an initial design of 12 slot, 10 pole outer-rotor field-excitation flux switching motor (FEFSM) with two different rotor width based from 2 different formula to design the rotor width. Hence, initial design include the three coil test to determine the U, W, V-phase, the flux strengthening and weakening, flux at various armature coil and field-excitation coil current, and finally the torque at various JA and JE. As for the materials, the stator and rotor consists of steel sheets made of electromagnetic steels, copper for armature coils and field excitation coils as the only field for magnetic flux source. There will be some design specification and restriction on outer-rotor FEFSM based on 2D-Finite Element Analysis will be applied to design the proposed machine.

In Vivo Magnetic Stimulation of Rat Sciatic Nerve With Centimeter- and Millimeter-Scale Solenoid Coils.

PubMed

Kagan, Zachary B; RamRakhyani, Anil Kumar; Lazzi, Gianluca; Normann, Richard A; Warren, David J

2016-11-01

Previous reports of magnetic stimulation of the peripheral nervous system (PNS) used various coil geometries, all with outer diameters larger than 35 mm, and stimulation energies in the 50 J range to evoke neural excitation. Recent reports of central nervous system (CNS) activation used sub-mm-scale solenoid coils with mJ energy levels. The goal of this study was to translate the lower energy levels from the CNS to the PNS via using smaller coils placed in closer proximity to the neural tissue. Such a performance improvement would advance the state of the art of magnetic stimulation and provide a path towards new neuroprosthetic devices. Primarily, we investigated the range of coil outer diameters from 25 mm down to 5 mm to better understand the dependence of coil diameter on energy required for PNS activation. Nine cm- and mm-scale copper solenoid coils, with various resistances, inductances, inner and outer diameters, and heights were compared by quantizing neuromuscular responses to magnetic stimulation via capacitive discharge excitation of rat sciatic nerves in vivo. Additionally, the effects of stimulus duration and coil position were investigated. As opposed to prior work, this study compares a subset of stimulation parameters in an intact nerve preparation, and shows that magnetic stimulation with coils that abut the nerve is a reliable, effective method of neuromuscular stimulation. Although we observed different energies required for neuromuscular activation depending on the coil and excitation parameters used, for the experimental configuration, devices, and stimulus waveform shapes presented in this manuscript, no systematic dependence of PNS activation on coil diameter was found, even for the mm-scale coils investigated herein. However, there was a clear relationship between discharge circuit capacitance and energy required to evoke a neuromuscular response. Coils approximately 12 mm in outer diameter and larger consistently evoked responses, whereas coils 5 mm in outer diameter did not. Furthermore, we observed meaningful neuromuscular excitation when stimulating with energies as low as 20 J. Although this is an improvement over prior work, it is still orders of magnitude greater than the energy required for conventional electrical stimulation, suggesting that these devices are presently not suitable for use in an application requiring continued pulsed stimulation. Nevertheless, these devices are suitable for basic research and as clinical tools that infrequently stimulate, such as in diagnostic applications.

Electromagnetic characteristics of eccentric figure-eight coils for transcranial magnetic stimulation: A numerical study

NASA Astrophysics Data System (ADS)

Kato, Takuya; Sekino, Masaki; Matsuzaki, Taiga; Nishikawa, Atsushi; Saitoh, Youichi; Ohsaki, Hiroyuki

2012-04-01

Repetitive transcranial magnetic stimulation (rTMS) is effective for treatment of several neurological and psychiatric diseases. We proposed an eccentric figure-eight coil, which induces strong eddy currents in the target brain tissue. In this study, numerical analyses were carried out to obtain magnetic field distribution of the eccentric figure-eight coil and eddy current in the brain. The analyses were performed with various coil design parameters, such as the outer and inner diameters and number of turns, to investigate the influence of these parameters on the coil characteristics. Increases in the inner diameter, outer diameter, and number of turns caused increases in the maximum eddy current densities. Coil inductance, working voltage, and heat generation also became higher with the increases in these design parameters. In order to develop a compact stimulator system for use at home, we need to obtain strong eddy current density, keeping the working voltage as low as possible. Our results show that it is effective to enlarge the outer diameter.

Control advances for achieving the ITER baseline scenario on KSTAR

NASA Astrophysics Data System (ADS)

Eidietis, N. W.; Barr, J.; Hahn, S. H.; Humphreys, D. A.; in, Y. K.; Jeon, Y. M.; Lanctot, M. J.; Mueller, D.; Walker, M. L.

2017-10-01

Control methodologies developed to enable successful production of ITER baseline scenario (IBS) plasmas on the superconducting KSTAR tokamak are presented: decoupled vertical control (DVC), real-time feedforward (rtFF) calculation, and multi-input multi-output (MIMO) X-point control. DVC provides fast vertical control with the in-vessel control coils (IVCC) while sharing slow vertical control with the poloidal field (PF) coils to avoid IVCC saturation. rtFF compensates for inaccuracies in offline PF current feedforward programming, allowing reduction or removal of integral gain (and its detrimental phase lag) from the shape controller. Finally, MIMO X-point control provides accurate positioning of the X-point despite low controllability due to the large distance between coils and plasma. Combined, these techniques enabled achievement of IBS parameters (q95 = 3.2, βN = 2) with a scaled ITER shape on KSTAR. n =2 RMP response displays a strong dependence upon this shaping. Work supported by the US DOE under Award DE-SC0010685 and the KSTAR project.

Design of snowflake-diverted equilibria of CFETR

NASA Astrophysics Data System (ADS)

Hang, LI; Xiang, GAO; Guoqiang, LI; Zhengping, LUO; Damao, YAO; Yong, GUO

2018-03-01

The Chinese Fusion Engineering Test Reactor (CFETR) represents the next generation of full superconducting fusion reactors in China. Recently, CFETR was redesigned with a larger size and will be operated in two phases. To reduce the heat flux on the target plate, a snowflake (SF) divertor configuration is proposed. In this paper we show that by adding two dedicated poloidal field (PF) coils, the SF configuration can be achieved in both phases. The equilibria were calculated by TEQ code for a range of self-inductances l i3. The coil currents were calculated at some fiducial points in the flattop phase. The results indicate that the PF coil system has the ability to maintain a long flattop phase in 7.5 and 10 MA inductive scenarios for the single null divertor (SND) and SF divertor configurations. The properties of the SF configuration were also analyzed. The connection length and flux expansion of the SF divertor were both increased significantly over the SND.

Superconducting magnetic energy storage apparatus structural support system

DOEpatents

Withers, Gregory J.; Meier, Stephen W.; Walter, Robert J.; Child, Michael D.; DeGraaf, Douglas W.

1992-01-01

A superconducting magnetic energy storage apparatus comprising a cylindrical superconducting coil; a cylindrical coil containment vessel enclosing the coil and adapted to hold a liquid, such as liquefied helium; and a cylindrical vacuum vessel enclosing the coil containment vessel and located in a restraining structure having inner and outer circumferential walls and a floor; the apparatus being provided with horizontal compression members between (1) the coil and the coil containment vessel and (2) between the coil containment vessel and the vacuum vessel, compression bearing members between the vacuum vessel and the restraining structure inner and outer walls, vertical support members (1) between the coil bottom and the coil containment vessel bottom and (2) between the coil containment vessel bottom and the vacuum vessel bottom, and external supports between the vacuum vessel bottom and the restraining structure floor, whereby the loads developed by thermal and magnetic energy changes in the apparatus can be accommodated and the structural integrity of the apparatus be maintained.

Harmonics analysis of the ITER poloidal field converter based on a piecewise method

NASA Astrophysics Data System (ADS)

Xudong, WANG; Liuwei, XU; Peng, FU; Ji, LI; Yanan, WU

2017-12-01

Poloidal field (PF) converters provide controlled DC voltage and current to PF coils. The many harmonics generated by the PF converter flow into the power grid and seriously affect power systems and electric equipment. Due to the complexity of the system, the traditional integral operation in Fourier analysis is complicated and inaccurate. This paper presents a piecewise method to calculate the harmonics of the ITER PF converter. The relationship between the grid input current and the DC output current of the ITER PF converter is deduced. The grid current is decomposed into the sum of some simple functions. By calculating simple function harmonics based on the piecewise method, the harmonics of the PF converter under different operation modes are obtained. In order to examine the validity of the method, a simulation model is established based on Matlab/Simulink and a relevant experiment is implemented in the ITER PF integration test platform. Comparative results are given. The calculated results are found to be consistent with simulation and experiment. The piecewise method is proved correct and valid for calculating the system harmonics.

Double layer field shaping systems for toroidal plasmas

DOEpatents

Ohyabu, Nobuyoshi

1982-01-01

Methods and apparatus for plasma generation, confinement and control such as Tokamak plasma systems are described having a two layer field shaping coil system comprising an inner coil layer close to the plasma and an outer coil layer to minimize the current in the inner coil layer.

Highly expressed EGFR in pearl sac may facilitate the pearl formation in the pearl oyster, Pinctada fucata.

PubMed

Zhu, Wenjie; Fan, Sigang; Huang, Guiju; Zhang, Dongling; Liu, Baosuo; Bi, Xiaomin; Yu, Dahui

2015-07-25

Epidermal growth factor receptor (EGFR) plays an important role in cell growth, proliferation, differentiation and migration. Yet whether it functions in pearl formation or not is not reported. In this study, EGFR was cloned from the pearl oyster Pinctada fucata (named as Pf-EGFR) and its expression profiles were investigated. The cDNA was 2156bp long with an ORF of 1017bp encoding 338 amino acid residues. The deduced polypeptide contained an L domain and a cysteine-rich domain, consistent with the characteristics of ErbB family. The sequence of Pf-EGFR shared 22.78-56.71% identity with other EGFRs. The genomic sequence of Pf-EGFR consisted of six exons and five introns, being 5190bp in total length, and expressed in all the tested tissues with a higher expression level in the pearl sac (P<0.05). In situ hybridization showed that Pf-EGFR was specifically expressed on both the inner side of the outer fold and the outer side of the inner fold of the mantle, as well as on the whole pearl sac including the connective tissues. In addition, Pf-EGFR was markedly increased at larval metamorphosis, significantly higher than other development periods (P<0.05). These results indicated that the Pf-EGFR may facilitate pearl formation as well as larval metamorphosis. Copyright © 2015 Elsevier B.V. All rights reserved.

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

Henning, C.

This report contains papers on the following topics: conceptual design; radiation damage of ITER magnet systems; insulation system of the magnets; critical current density and strain sensitivity; toroidal field coil structural analysis; stress analysis for the ITER central solenoid; and volt-second capabilities and PF magnet configurations.

Design and use of a folded four-ring double-tuned birdcage coil for rat brain sodium imaging at 9.4 T

NASA Astrophysics Data System (ADS)

Ha, YongHyun; Choi, Chang-Hoon; Worthoff, Wieland A.; Shymanskaya, Aliaksandra; Schöneck, Michael; Willuweit, Antje; Felder, Jörg; Shah, N. Jon

2018-01-01

A folded four-ring quadrature birdcage coil was designed and constructed with a double-tune configuration of an outer high-pass coil for 1H (400 MHz) and inner low-pass coil for 23Na (105.72 MHz at 9.4 T). The coil was evaluated on the bench and in the scanner, comparing its performance with that of single-tuned coils and a large four-ring coil. All coils were tuned and matched and the isolation between two quadrature ports was found to be better than -13.7 dB for 1H and -27 dB for 23Na. Signal-to-noise ratios (SNRs) were calculated and 23Na flip angle maps were acquired. 23Na SNR of the folded four-ring reached ∼93% of that obtained with the single-tuned coil. A set of in vivo1H and 23Na axial images to cover the whole rat brain were obtained. The performance of the folded four-ring coil and its benefit for 23Na imaging experiments have been demonstrated. This proposed four-ring coil could avoid length restrictions, e.g. the shoulders, by folding the outer rings vertically. This facilitates the construction of double-tuned four-ring birdcage coils just to fit the head, leading to higher filling factors and better SNR.

Design and use of a folded four-ring double-tuned birdcage coil for rat brain sodium imaging at 9.4 T.

PubMed

Ha, YongHyun; Choi, Chang-Hoon; Worthoff, Wieland A; Shymanskaya, Aliaksandra; Schöneck, Michael; Willuweit, Antje; Felder, Jörg; Shah, N Jon

2018-01-01

A folded four-ring quadrature birdcage coil was designed and constructed with a double-tune configuration of an outer high-pass coil for 1 H (400 MHz) and inner low-pass coil for 23 Na (105.72 MHz at 9.4 T). The coil was evaluated on the bench and in the scanner, comparing its performance with that of single-tuned coils and a large four-ring coil. All coils were tuned and matched and the isolation between two quadrature ports was found to be better than -13.7 dB for 1 H and -27 dB for 23 Na. Signal-to-noise ratios (SNRs) were calculated and 23 Na flip angle maps were acquired. 23 Na SNR of the folded four-ring reached ∼93% of that obtained with the single-tuned coil. A set of in vivo 1 H and 23 Na axial images to cover the whole rat brain were obtained. The performance of the folded four-ring coil and its benefit for 23 Na imaging experiments have been demonstrated. This proposed four-ring coil could avoid length restrictions, e.g. the shoulders, by folding the outer rings vertically. This facilitates the construction of double-tuned four-ring birdcage coils just to fit the head, leading to higher filling factors and better SNR. Copyright © 2017 Elsevier Inc. All rights reserved.

Measurement of AC Losses in a Racetrack Superconducting Coil Made from YBCO Coated Conductor

NASA Astrophysics Data System (ADS)

Seiler, Eugen; Abrahamsen, Asger B.; Kováč, Ján; Wichmann, Mike; Træholt, Chresten

We present the results of transport measurements of AC losses in a racetrack shaped superconducting coil made from coated conductor tape. The outer dimensions of the coil are approximately 24 cm × 12 cm and it has 57 turns. The coil is impregnated with epoxy resin and fiberglass tape is used to insulate the individual turns and to improve the mechanical properties of the epoxy when exposed to thermal cycling. The coil is manufactured as a part of the field winding of a small synchronous generator; therefore stainless steel frames are installed on the inner and outer side of the winding to reinforce it. The AC loss is measured versus the transport current Ia with the coil immersed in liquid nitrogen. Measurements at frequencies 21 Hz, 36 Hz and 72 Hz are compared. The AC losses follow Ia2 dependence at low current amplitudes and Ia3 at high amplitudes. After cutting the inner steel frame the low amplitude losses are decreased, their frequency dependence is reduced but their dependence on the current remains unchanged.

Thin film eddy current impulse deicer

NASA Technical Reports Server (NTRS)

Smith, Samuel O.; Zieve, Peter B.

1990-01-01

Two new styles of electrical impulse deicers has been developed and tested in NASA's Icing Research Tunnel. With the Eddy Current Repulsion Deicing Boot (EDB), a thin and flexible spiral coil is encapsulated between two thicknesses of elastomer. The coil, made by an industrial printed circuit board manufacturer, is bonded to the aluminum aircraft leading edge. A capacitor bank is discharged through the coil. Induced eddy currents repel the coil from the aluminum aircraft structure and shed accumulated ice. A second configuration, the Eddy Current Repulsion Deicing-Strip (EDS) uses an outer metal erosion strip fastened over the coil. Opposite flowing eddy currents repel the strip and create the impulse deicing force. The outer strip serves as a surface for the collection and shedding of ice and does not require any structural properties. The EDS is suitable for composite aircraft structures. Both systems successfully dispelled over 95 percent of the accumulated ice from airfoils over the range of the FAA icing envelope.

ITER Side Correction Coil Quench model and analysis

NASA Astrophysics Data System (ADS)

Nicollet, S.; Bessette, D.; Ciazynski, D.; Duchateau, J. L.; Gauthier, F.; Lacroix, B.

2016-12-01

Previous thermohydraulic studies performed for the ITER TF, CS and PF magnet systems have brought some important information on the detection and consequences of a quench as a function of the initial conditions (deposited energy, heated length). Even if the temperature margin of the Correction Coils is high, their behavior during a quench should also be studied since a quench is likely to be triggered by potential anomalies in joints, ground fault on the instrumentation wires, etc. A model has been developed with the SuperMagnet Code (Bagnasco et al., 2010) for a Side Correction Coil (SCC2) with four pancakes cooled in parallel, each of them represented by a Thea module (with the proper Cable In Conduit Conductor characteristics). All the other coils of the PF cooling loop are hydraulically connected in parallel (top/bottom correction coils and six Poloidal Field Coils) are modeled by Flower modules with equivalent hydraulics properties. The model and the analysis results are presented for five quench initiation cases with/without fast discharge: two quenches initiated by a heat input to the innermost turn of one pancake (case 1 and case 2) and two other quenches initiated at the innermost turns of four pancakes (case 3 and case 4). In the 5th case, the quench is initiated at the middle turn of one pancake. The impact on the cooling circuit, e.g. the exceedance of the opening pressure of the quench relief valves, is detailed in case of an undetected quench (i.e. no discharge of the magnet). Particular attention is also paid to a possible secondary quench detection system based on measured thermohydraulic signals (pressure, temperature and/or helium mass flow rate). The maximum cable temperature achieved in case of a fast current discharge (primary detection by voltage) is compared to the design hot spot criterion of 150 K, which includes the contribution of helium and jacket.

Developing Test Apparatus and Measurements of AC Loss of High Temperature Superconductors

DTIC Science & Technology

2012-11-01

temperature of the coil is not raised significantly. The second system, a larger machine, designed with a long term prospective to serve a test bed for...four sample chambers inside the vacuum gap, LN2 – cooled sample holder (currently only one is in use), the laminated back iron, and the outer shell...machine. accommodate a variety of different small coils and linear tapes. This assembly is surrounded by the laminated back iron and the outer shell

Nuclear reactor safety device

DOEpatents

Hutter, Ernest

1986-01-01

A safety device is disclosed for use in a nuclear reactor for axially repositioning a control rod with respect to the reactor core in the event of an upward thermal excursion. Such safety device comprises a laminated helical ribbon configured as a tube-like helical coil having contiguous helical turns with slidably abutting edges. The helical coil is disclosed as a portion of a drive member connected axially to the control rod. The laminated ribbon is formed of outer and inner laminae. The material of the outer lamina has a greater thermal coefficient of expansion than the material of the inner lamina. In the event of an upward thermal excursion, the laminated helical coil curls inwardly to a smaller diameter. Such inward curling causes the total length of the helical coil to increase by a substantial increment, so that the control rod is axially repositioned by a corresponding amount to reduce the power output of the reactor.

Superconducting coil and method of stress management in a superconducting coil

DOEpatents

McIntyre, Peter M.; Shen, Weijun; Diaczenko, Nick; Gross, Dan A.

1999-01-01

A superconducting coil (12) having a plurality of superconducting layers (18) is provided. Each superconducting layer (18) may have at least one superconducting element (20) which produces an operational load. An outer support structure (24) may be disposed outwardly from the plurality of layers (18). A load transfer system (22) may be coupled between at least one of the superconducting elements (20) and the outer support structure (24). The load transfer system (22) may include a support matrix structure (30) operable to transfer the operational load from the superconducting element (20) directly to the outer support structure (24). A shear release layer (40) may be disposed, in part, between the superconducting element (20) and the support matrix structure (30) for relieving a shear stress between the superconducting element (20) and the support matrix structure (30). A compliant layer (42) may also be disposed, in part, between the superconducting element (20) and the support matrix structure (30) for relieving a compressive stress on the superconducting element (20).

Plasma confinement system and methods for use

DOEpatents

Jarboe, Thomas R.; Sutherland, Derek

2017-09-05

A plasma confinement system is provided that includes a confinement chamber that includes one or more enclosures of respective helicity injectors. The one or more enclosures are coupled to ports at an outer radius of the confinement chamber. The system further includes one or more conductive coils aligned substantially parallel to the one or more enclosures and a further set of one or more conductive coils respectively surrounding portions of the one or more enclosures. Currents may be provided to the sets of conductive coils to energize a gas within the confinement chamber into a plasma. Further, a heat-exchange system is provided that includes an inner wall, an intermediate wall, an outer wall, and pipe sections configured to carry coolant through cavities formed by the walls.

High-field double-pancake superconducting coils and a method of winding

DOEpatents

Materna, P.A.

1984-01-31

A double-pancake coil having first and second pancakes may comprise a plurality of conductor means, each conductor means having a different grade and having one or more conductors, wherein each pancake of said double-pancake coil is comprised of inner and outer turns; wherein said inner turns are comprised of at least one of said conductor means wound about an axis and nested within one another; wherein said outer turns are comprised of said inner conductor means and at least one other conductor means co-wound about said inner turns and nested within one another; wherein each of said conductor means is wound along said axis from said first pancake to said second pancake at a different turn.

High-field double-pancake superconducting coils and a method of winding

DOEpatents

Materna, Peter A.

1985-01-01

A double-pancake coil having first and second pancakes may comprise a plurality of conductor means, each conductor means having a different grade and having one or more conductors, wherein each pancake of said double-pancake coil is comprised of inner and outer turns; wherein said inner turns are comprised of at least one of said conductor means wound about an axis and nested within one another; wherein said outer turns are comprised of said inner conductor means and at least one other conductor means co-wound about said inner turns and nested within one another; wherein each of said conductor means is wound along said axis from said first pancake to said second pancake at a different turn.

pF3D Simulations of Large Outer-Beam Brillouin Scattering from NIF Rugby Hohlraums

NASA Astrophysics Data System (ADS)

Langer, Steven; Strozzi, David; Chapman, Thomas; Amendt, Peter

2015-11-01

We assess the cause of large outer-beam stimulated Brillouin scattering (SBS) in a NIF shot with a rugby-shaped hohlraum, which has less wall surface loss and thus higher x-ray drive than a cylindrical hohlraum of the same radius. This shot differed from a prior rugby shot with low SBS in three ways: outer beam pointing, split-pointing of the four beams within each outer-beam quadruplet, and a small amount of neon added to the hohlraum helium fill gas. We use pF3D, a massively-parallel, paraxial-envelope laser plasma interaction code, with plasma profiles from the radiation-hydrodynamics code Lasnex. We determine which change between the two shots increased the SBS by adding them one at a time to the simulations. We compare the simulations to experimental data for total SBS power, its spatial distribution at the lens, and the SBS spectrum. For each shot, we use profiles from Lasnex simulations with and without a model for mix at the hohlraum wall-gas interface. Work performed under the auspices of the U.S. Department of Energy by LLNL under Contract DE-AC52-07NA27344. Release number LLNL-ABS-674893.

Low-pressure water-cooled inductively coupled plasma torch

DOEpatents

Seliskar, C.J.; Warner, D.K.

1984-02-16

An inductively coupled plasma torch is provided which comprises an inner tube, including a sample injection port to which the sample to be tested is supplied and comprising an enlarged central portion in which the plasma flame is confined; an outer tube surrounding the inner tube and containing water therein for cooling the inner tube, the outer tube including a water inlet port to which water is supplied and a water outlet port spaced from the water inlet port and from which water is removed after flowing through the outer tube; and an rf induction coil for inducing the plasma in the gas passing into the tube through the sample injection port. The sample injection port comprises a capillary tube including a reduced diameter orifice, projecting into the lower end of the inner tube. The water inlet is located at the lower end of the outer tube and the rf heating coil is disposed around the outer tube above and adjacent to the water inlet.

Low-pressure water-cooled inductively coupled plasma torch

DOEpatents

Seliskar, Carl J.; Warner, David K.

1988-12-27

An inductively coupled plasma torch is provided which comprises an inner tube, including a sample injection port to which the sample to be tested is supplied and comprising an enlarged central portion in which the plasma flame is confined; an outer tube surrounding the inner tube and containing water therein for cooling the inner tube, the outer tube including a water inlet port to which water is supplied and a water outlet port spaced from the water inlet port and from which water is removed after flowing through the outer tube; and an r.f. induction coil for inducing the plasma in the gas passing into the tube through the sample injection port. The sample injection port comprises a capillary tube including a reduced diameter orifice, projecting into the lower end of the inner tube. The water inlet is located at the lower end of the outer tube and the r.f. heating coil is disposed around the outer tube above and adjacent to the water inlet.

Permanent magnet machine with windings having strand transposition

DOEpatents

Qu, Ronghai; Jansen, Patrick Lee

2009-04-21

This document discusses, among other things, a stator with transposition between the windings or coils. The coils are free from transposition to increase the fill factor of the stator slots. The transposition at the end connections between an inner coil and an outer coil provide transposition to reduce circulating current loss. The increased fill factor reduces further current losses. Such a stator is used in a dual rotor, permanent magnet machine, for example, in a compressor pump, wind turbine gearbox, wind turbine rotor.

Metallic Induction Reaction Engine.

DTIC Science & Technology

1984-12-28

FODA CLAIJ TY Figure 2: Experimental Setup 2 A EML Research Metallic Induction Reaction Engine page 3 Figure 3: Aluminum Reaction Mass Ring in Flight...reaction mass materials. Furthur analysis performed with the *] numerical model indicates that there exists a back EMF saturation effect which inhibits the...instrumentation difficulties, a detailed analysis of it’s performance has not been established. r Outer Coil Projectile- Coil Inner Coil Figure 4

Challenges and status of ITER conductor production

NASA Astrophysics Data System (ADS)

Devred, A.; Backbier, I.; Bessette, D.; Bevillard, G.; Gardner, M.; Jong, C.; Lillaz, F.; Mitchell, N.; Romano, G.; Vostner, A.

2014-04-01

Taking the relay of the large Hadron collider (LHC) at CERN, ITER has become the largest project in applied superconductivity. In addition to its technical complexity, ITER is also a management challenge as it relies on an unprecedented collaboration of seven partners, representing more than half of the world population, who provide 90% of the components as in-kind contributions. The ITER magnet system is one of the most sophisticated superconducting magnet systems ever designed, with an enormous stored energy of 51 GJ. It involves six of the ITER partners. The coils are wound from cable-in-conduit conductors (CICCs) made up of superconducting and copper strands assembled into a multistage cable, inserted into a conduit of butt-welded austenitic steel tubes. The conductors for the toroidal field (TF) and central solenoid (CS) coils require about 600 t of Nb3Sn strands while the poloidal field (PF) and correction coil (CC) and busbar conductors need around 275 t of Nb-Ti strands. The required amount of Nb3Sn strands far exceeds pre-existing industrial capacity and has called for a significant worldwide production scale up. The TF conductors are the first ITER components to be mass produced and are more than 50% complete. During its life time, the CS coil will have to sustain several tens of thousands of electromagnetic (EM) cycles to high current and field conditions, way beyond anything a large Nb3Sn coil has ever experienced. Following a comprehensive R&D program, a technical solution has been found for the CS conductor, which ensures stable performance versus EM and thermal cycling. Productions of PF, CC and busbar conductors are also underway. After an introduction to the ITER project and magnet system, we describe the ITER conductor procurements and the quality assurance/quality control programs that have been implemented to ensure production uniformity across numerous suppliers. Then, we provide examples of technical challenges that have been encountered and we present the status of ITER conductor production worldwide.

Transepithelial water and urea permeabilities of isolated perfused Munich-Wistar rat inner medullary thin limbs of Henle's loop.

PubMed

Nawata, C Michele; Evans, Kristen K; Dantzler, William H; Pannabecker, Thomas L

2014-01-01

To better understand the role that water and urea fluxes play in the urine concentrating mechanism, we determined transepithelial osmotic water permeability (Pf) and urea permeability (Purea) in isolated perfused Munich-Wistar rat long-loop descending thin limbs (DTLs) and ascending thin limbs (ATLs). Thin limbs were isolated either from 0.5 to 2.5 mm below the outer medulla (upper inner medulla) or from the terminal 2.5 mm of the inner medulla. Segment types were characterized on the basis of structural features and gene expression levels of the water channel aquaporin 1, which was high in the upper DTL (DTLupper), absent in the lower DTL (DTLlower), and absent in ATLs, and the Cl-(1) channel ClCK1, which was absent in DTLs and high in ATLs. DTLupper Pf was high (3,204.5 ± 450.3 μm/s), whereas DTLlower showed very little or no osmotic Pf (207.8 ± 241.3 μm/s). Munich-Wistar rat ATLs have previously been shown to exhibit no Pf. DTLupper Purea was 40.0 ± 7.3 × 10(-5) cm/s and much higher in DTLlower (203.8 ± 30.3 × 10(-5) cm/s), upper ATL (203.8 ± 35.7 × 10(-5) cm/s), and lower ATL (265.1 ± 49.8 × 10(-5) cm/s). Phloretin (0.25 mM) did not reduce DTLupper Purea, suggesting that Purea is not due to urea transporter UT-A2, which is expressed in short-loop DTLs and short portions of some inner medullary DTLs close to the outer medulla. In summary, Purea is similar in all segments having no osmotic Pf but is significantly lower in DTLupper, a segment having high osmotic Pf. These data are inconsistent with the passive mechanism as originally proposed.

HYPOTONIC SWELLING OF SALICYLATE-TREATED COCHLEAR OUTER HAIR CELLS

PubMed Central

Zhi, Man; Ratnanather, J. Tilak; Ceyhan, Elvan; Popel, Aleksander S.; Brownell, William E.

2007-01-01

The outer hair cell (OHC) is a hydrostat with a low hydraulic conductivity of Pf = 3×10−4 cm/s across the plasma membrane (PM) and subsurface cisterna (SSC) that make up the OHC's lateral wall. The SSC is structurally and functionally a transport barrier in normal cells that is known to be disrupted by salicylate. The effect of sodium salicylate on Pf is determined from osmotic experiments in which isolated, control and salicylate-treated OHCs were exposed to hypotonic solutions in a constant flow chamber. The value of Pf = 3.5±0.5 ×10−4 cm/s (mean ± s.e.m, n = 34) for salicylate-treated OHCs was not significantly different from Pf = 2.4±0.3 ×10−4 cm/s (mean ± s.e.m, n = 31) for untreated OHCs (p=.3302). Thus Pf is determined by the PM and is unaffected by salicylate treatment. The ratio of longitudinal strain to radial strain εz/εc = −0.76 for salicylate-treated OHCs was significantly smaller (p = .0143) from −0.72 for untreated OHCs, and is also independent of the magnitude of the applied osmotic challenge. Salicylate-treated OHCs took longer to attain a steady-state volume which is larger than that for untreated OHCs and increased in volume by 8-15% prior to hypotonic perfusion unlike sodium α-ketoglutarate treated OHCs. It is suggested that depolymerization of cytoskeletal proteins and/or glycogen maybe responsible for the large volume increase in salicylate-treated OHCs as well as the different responses to different modes of application of the hypotonic solution. PMID:17400411

NASA superconducting magnetic mirror facility

NASA Technical Reports Server (NTRS)

Reinmann, J. J.; Swanson, M. C.; Nichols, C. R.; Obloy, S. J.; Nagy, L. A.; Brady, F. J.

1973-01-01

This report summarizes the design details and initial test results of a superconducting magnetic mirror facility that has been constructed at NASA Lewis Research Center for use in thermonuclear research. The magnet system consists of four solenoidal coils which are individually rated at 5.0 T. Each coil is composed of an inner, middle, and outer winding. The inner winding is wound of stabilized Nb3SN superconducting ribbon, and the middle and outer windings are wound of stabilized Nb-Ti superconducting wire. When arranged in the mirror geometry, the four coils will produce 8.7 T at the mirrors and a 1.8 mirror ratio. The magnet has a 41-cm diameter clear bore which is open to atmosphere. Distance between the mirrors is 111 cm. Presently there are only three magnets in the facility; the fourth magnet is being rebuilt.

Suppressor Analysis of the Fusogenic Lambda Spanins.

PubMed

Cahill, Jesse; Rajaure, Manoj; Holt, Ashley; Moreland, Russell; O'Leary, Chandler; Kulkarni, Aneesha; Sloan, Jordan; Young, Ry

2017-07-15

The final step of lysis in phage λ infections of Escherichia coli is mediated by the spanins Rz and Rz1. These proteins form a complex that bridges the cell envelope and that has been proposed to cause fusion of the inner and outer membranes. Accordingly, mutations that block spanin function are found within coiled-coil domains and the proline-rich region, motifs essential in other fusion systems. To gain insight into spanin function, pseudorevertant alleles that restored plaque formation for lysis-defective mutants of Rz and Rz1 were selected. Most second-site suppressors clustered within a coiled-coil domain of Rz near the outer leaflet of the cytoplasmic membrane and were not allele specific. Suppressors largely encoded polar insertions within the hydrophobic core of the coiled-coil interface. Such suppressor changes resulted in decreased proteolytic stability of the Rz double mutants in vivo Unlike the wild type, in which lysis occurs while the cells retain a rod shape, revertant alleles with second-site suppressor mutations supported lysis events that were preceded by spherical cell formation. This suggests that destabilization of the membrane-proximal coiled coil restores function for defective spanin alleles by increasing the conformational freedom of the complex at the cost of its normal, all-or-nothing functionality. IMPORTANCE Caudovirales encode cell envelope-spanning proteins called spanins, which are thought to fuse the inner and outer membranes during phage lysis. Recent genetic analysis identified the functional domains of the lambda spanins, which are similar to class I viral fusion proteins. While the pre- and postfusion structures of model fusion systems have been well characterized, the intermediate structure(s) formed during the fusion reaction remains elusive. Genetic analysis would be expected to identify functional connections between intermediates. Since most membrane fusion systems are not genetically tractable, only few such investigations have been reported. Here, we report a suppressor analysis of lambda spanin function. To our knowledge this is the first suppression analysis of a class I-like complex and also the first such analysis of a prokaryote membrane fusion system. Copyright © 2017 American Society for Microbiology.

Improvement of wireless power transmission efficiency of implantable subcutaneous devices by closed magnetic circuit mechanism.

PubMed

Jo, Sung-Eun; Joung, Sanghoon; Suh, Jun-Kyo Francis; Kim, Yong-Jun

2012-09-01

Induction coils were fabricated based on flexible printed circuit board for inductive transcutaneous power transmission. The coil had closed magnetic circuit (CMC) structure consisting of inner and outer magnetic core. The power transmission efficiency of the fabricated device was measured in the air and in vivo condition. It was confirmed that the CMC coil had higher transmission efficiency than typical air-core coil. The power transmission efficiency during a misalignment between primary coil and implanted secondary coil was also evaluated. The decrease of mutual inductance between the two coils caused by the misalignment led to a low efficiency of the inductive link. Therefore, it is important to properly align the primary coil and implanted secondary coil for effective power transmission. To align the coils, a feedback coil was proposed. This was integrated on the backside of the primary coil and enabled the detection of a misalignment of the primary and secondary coils. As a result of using the feedback coil, the primary and secondary coils could be aligned without knowledge of the position of the implanted secondary coil.

Beam heated linear theta-pinch device for producing hot plasmas

DOEpatents

Bohachevsky, Ihor O.

1981-01-01

A device for producing hot plasmas comprising a single turn theta-pinch coil, a fast discharge capacitor bank connected to the coil, a fuel element disposed along the center axis of the coil, a predetermined gas disposed within the theta-pinch coil, and a high power photon, electron or ion beam generator concentrically aligned to the theta-pinch coil. Discharge of the capacitor bank generates a cylindrical plasma sheath within the theta-pinch coil which heats the outer layer of the fuel element to form a fuel element plasma layer. The beam deposits energy in either the cylindrical plasma sheath or the fuel element plasma layer to assist the implosion of the fuel element to produce a hot plasma.

Generating an AC amplitude magnetic flux density value up to 150 μT at a frequency up to 100 kHz

NASA Astrophysics Data System (ADS)

Ulvr, Michal; Polonský, Jakub

2017-05-01

AC magnetic field analyzers with a triaxial coil probe are widely used by health and safety professionals, in manufacturing, and in service industries. For traceable calibration of these analyzers, it is important to be able to generate a stable, homogeneous reference AC magnetic flux density (MFD). In this paper, the generating of AC amplitude MFD value of 150 μT by single-layer Helmholtz type solenoid, described in previous work, was expanded up to a frequency of 100 kHz using the effect of serial resonance. A programmable capacitor array has been developed with a range of adjustable values from 50 pF to 51225 pF. In addition, the multi-layer search coil with a nominal area turns value of 1.3m2, used for adjusting AC MFD in the solenoid, has been modified by a transimpedance amplifier for use in a wider frequency range than up to 3 kHz. The possibility of using the programmable capacitor array up to 150 kHz has also been tested. An AC amplitude MFD value of 150 μT can be generated with expanded uncertainty better than 0.6% up to 100 kHz.

Study on a New Combination Method and High Efficiency Outer Rotor Type Permanent Magnet Motors

NASA Astrophysics Data System (ADS)

Enomoto, Yuji; Kitamura, Masashi; Motegi, Yasuaki; Andoh, Takashi; Ochiai, Makoto; Abukawa, Toshimi

The segment stator core, high space factor coil, and high efficiency magnet are indispensable technologies in the development of compact and a high efficiency motors. But adoption of the segment stator core and high space factor coil has not progressed in the field of outer rotor type motors, for the reason that the inner components cannot be laser welded together. Therefore, we have examined a segment stator core combination technology for the purposes of getting a large increase in efficiency and realizing miniaturization. We have also developed a characteristic estimation method which provides the most suitable performance for segment stator core motors.

Correction coil cable

DOEpatents

Wang, S.T.

1994-11-01

A wire cable assembly adapted for the winding of electrical coils is taught. A primary intended use is for use in particle tube assemblies for the Superconducting Super Collider. The correction coil cables have wires collected in wire array with a center rib sandwiched therebetween to form a core assembly. The core assembly is surrounded by an assembly housing having an inner spiral wrap and a counter wound outer spiral wrap. An alternate embodiment of the invention is rolled into a keystoned shape to improve radial alignment of the correction coil cable on a particle tube in a particle tube assembly. 7 figs.

Static current-voltage characteristics for radio-frequency induction discharge

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

Budyansky, A.; Zykov, A.

1995-12-31

The aim of this work was to obtain experimentally such characteristic of Radio-Frequency Induction Discharge (RFID) that can play the role of its current-voltage characteristic (CVC) and to explain the nature of current and voltage jumps arising in RF coils at exciting of discharge. Experiments were made in quartz 5.5, 11, 20 cm diam tubes with outer RF coil at pressures 10--100 mTorr, at frequency 13.56 MHz and discharge power to 500 W. In case of outer coil as analogue of discharge voltage it`s convenient to use the value of the RF voltage U{sub R}, induced around outer perimeter ofmore » discharge tube. It is evident that current and voltage jumps arising at exciting of discharge are due to low output resistance of standard generators and negative slope of initial part of CVC. Three sets of such dependencies for different pressures were obtained for each diameter of tubes. The influence of different metal electrodes placed into discharge volume on CVC`s shape has been studied also. Experimental results can explain the behavior of HFI discharge as a load of RF generator and give data for calculation of RF circuit.« less

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

Meinke, Rainer

A method for manufacture of a conductor assembly. The assembly is of the type which, when conducting current, generates a magnetic field or in which, in the presence of a changing magnetic field, a voltage is induced. In an example embodiment one or more first coil rows are formed. The assembly has multiple coil rows about an axis with outer coil rows formed about inner coil rows. A determination is made of deviations from specifications associated with the formed one or more first coil rows. One or more deviations correspond to a magnitude of a multipole field component which departsmore » from a field specification. Based on the deviations, one or more wiring patterns are generated for one or more second coil rows to be formed about the one or more first coil rows. The one or more second coil rows are formed in the assembly. The magnitude of each multipole field component that departs from the field specification is offset.« less

Turbulent convective heat transfer of methane at supercritical pressure in a helical coiled tube

NASA Astrophysics Data System (ADS)

Wang, Chenggang; Sun, Baokun; Lin, Wei; He, Fan; You, Yingqiang; Yu, Jiuyang

2018-02-01

The heat transfer of methane at supercritical pressure in a helically coiled tube was numerically investigated using the Reynolds Stress Model under constant wall temperature. The effects of mass flux ( G), inlet pressure ( P in) and buoyancy force on the heat transfer behaviors were discussed in detail. Results show that the light fluid with higher temperature appears near the inner wall of the helically coiled tube. When the bulk temperature is less than or approach to the pseudocritical temperature ( T pc ), the combined effects of buoyancy force and centrifugal force make heavy fluid with lower temperature appear near the outer-right of the helically coiled tube. Beyond the T pc , the heavy fluid with lower temperature moves from the outer-right region to the outer region owing to the centrifugal force. The buoyancy force caused by density variation, which can be characterized by Gr/ Re 2 and Gr/ Re 2.7, enhances the heat transfer coefficient ( h) when the bulk temperature is less than or near the T pc , and the h experiences oscillation due to the buoyancy force. The oscillation is reduced progressively with the increase of G. Moreover, h reaches its peak value near the T pc . Higher G could improve the heat transfer performance in the whole temperature range. The peak value of h depends on P in. A new correlation was proposed for methane at supercritical pressure convective heat transfer in the helical tube, which shows a good agreement with the present simulated results.

Characteristics of bowl-shaped coils for transcranial magnetic stimulation

NASA Astrophysics Data System (ADS)

Yamamoto, Keita; Suyama, Momoko; Takiyama, Yoshihiro; Kim, Dongmin; Saitoh, Youichi; Sekino, Masaki

2015-05-01

Transcranial magnetic stimulation (TMS) has recently been used as a method for the treatment of neurological and psychiatric diseases. Daily TMS sessions can provide continuous therapeutic effectiveness, and the installation of TMS systems at patients' homes has been proposed. A figure-eight coil, which is normally used for TMS therapy, induces a highly localized electric field; however, it is challenging to achieve accurate coil positioning above the targeted brain area using this coil. In this paper, a bowl-shaped coil for stimulating a localized but wider area of the brain is proposed. The coil's electromagnetic characteristics were analyzed using finite element methods, and the analysis showed that the bowl-shaped coil induced electric fields in a wider area of the brain model than a figure-eight coil. The expanded distribution of the electric field led to greater robustness of the coil to the coil-positioning error. To improve the efficiency of the coil, the relationship between individual coil design parameters and the resulting coil characteristics was numerically analyzed. It was concluded that lengthening the outer spherical radius and narrowing the width of the coil were effective methods for obtaining a more effective and more uniform distribution of the electric field.

Protective Effect of Highly Polymeric A-Type Proanthocyanidins from Seed Shells of Japanese Horse Chestnut (Aesculus turbinata BLUME) against Light-Induced Oxidative Damage in Rat Retina

PubMed Central

Ishihara, Tomoe; Kaidzu, Sachiko; Kimura, Hideto; Koyama, Yasurou; Matsuoka, Yotaro

2018-01-01

Retinal tissue is exposed to oxidative stress caused by visible light. Light-damaged rat used in age-related macular degeneration (AMD) studies clarified that antioxidants decrease retinal light damage. Albino rats were exposed to 5000 Lux light for 12 h with oral administration of the polyphenolic compounds fraction (PF) from the seed shells of Japanese horse chestnut (30 mg/kg, 100 mg/kg, and 300 mg/kg body weight: BW). To evaluate the protective effects against light damage, electroretinograms (ERGs), the outer nuclear layer (ONL) thickness, the antioxidant activity of plasma, oxidized retinal lipids, and the detection of apoptosis were examined. To reveal their active compounds, PF were separated into an A-type proanthocyanidin (PAF) and a flavonol O-glycosides fraction. The protective effects of these fractions against light damage were compared by measuring the thickness of the ERGs and ONL. Compared with the negative control, the PF group (100 mg/kg and 300 mg/kg BW) significantly suppressed the decrease of the ERG amplitudes and ONL thickness. PF (300 mg/kg BW) induced the elevation of in vivo antioxidant activity, and the suppression of retinal lipid oxidation. PF administration also suppressed apoptotic cell death. The protective effects against light damage were attributable to the antioxidant activity of PAF. The light-induced damage of retinas was protected by oral administration of PF and PAF. Taken together, these compounds are potentially useful for the prevention of the disease caused by light exposure. Highlights: The protective effects of retinal damage by light exposure were evaluated using polyphenolic compounds from the seed shells of Japanese horse chestnut (Aesculus turbinata BLUME) as an antioxidant. Decreases in the electroretinographic amplitude and outer nuclear layer thickness were suppressed by the polyphenolic compounds of the seed shells. Polyphenolic compounds from the seed shells of Japanese horse chestnut inhibited the oxidation of retinal lipids. Highly polymeric A-type proanthocyanidin from the seed shells protected the rat retina from light exposure damage by inhibiting oxidative stress and apoptotic mechanisms. PMID:29748512

Protective Effect of Highly Polymeric A-Type Proanthocyanidins from Seed Shells of Japanese Horse Chestnut (Aesculus turbinata BLUME) against Light-Induced Oxidative Damage in Rat Retina.

PubMed

Ishihara, Tomoe; Kaidzu, Sachiko; Kimura, Hideto; Koyama, Yasurou; Matsuoka, Yotaro; Ohira, Akihiro

2018-05-10

Retinal tissue is exposed to oxidative stress caused by visible light. Light-damaged rat used in age-related macular degeneration (AMD) studies clarified that antioxidants decrease retinal light damage. Albino rats were exposed to 5000 Lux light for 12 h with oral administration of the polyphenolic compounds fraction (PF) from the seed shells of Japanese horse chestnut (30 mg/kg, 100 mg/kg, and 300 mg/kg body weight: BW). To evaluate the protective effects against light damage, electroretinograms (ERGs), the outer nuclear layer (ONL) thickness, the antioxidant activity of plasma, oxidized retinal lipids, and the detection of apoptosis were examined. To reveal their active compounds, PF were separated into an A-type proanthocyanidin (PAF) and a flavonol O -glycosides fraction. The protective effects of these fractions against light damage were compared by measuring the thickness of the ERGs and ONL. Compared with the negative control, the PF group (100 mg/kg and 300 mg/kg BW) significantly suppressed the decrease of the ERG amplitudes and ONL thickness. PF (300 mg/kg BW) induced the elevation of in vivo antioxidant activity, and the suppression of retinal lipid oxidation. PF administration also suppressed apoptotic cell death. The protective effects against light damage were attributable to the antioxidant activity of PAF. The light-induced damage of retinas was protected by oral administration of PF and PAF. Taken together, these compounds are potentially useful for the prevention of the disease caused by light exposure. The protective effects of retinal damage by light exposure were evaluated using polyphenolic compounds from the seed shells of Japanese horse chestnut ( Aesculus turbinata BLUME) as an antioxidant. Decreases in the electroretinographic amplitude and outer nuclear layer thickness were suppressed by the polyphenolic compounds of the seed shells. Polyphenolic compounds from the seed shells of Japanese horse chestnut inhibited the oxidation of retinal lipids. Highly polymeric A-type proanthocyanidin from the seed shells protected the rat retina from light exposure damage by inhibiting oxidative stress and apoptotic mechanisms.

Self-Centering Reciprocating-Permanent-Magnet Machine

NASA Technical Reports Server (NTRS)

Bhate, Suresh; Vitale, Nick

1988-01-01

New design for monocoil reciprocating-permanent-magnet electric machine provides self-centering force. Linear permanent-magnet electrical motor includes outer stator, inner stator, and permanent-magnet plunger oscillateing axially between extreme left and right positions. Magnets arranged to produce centering force and allows use of only one coil of arbitrary axial length. Axial length of coil chosen to provide required efficiency and power output.

Flagellar central pair assembly in Chlamydomonas reinhardtii

PubMed Central

2013-01-01

Background Most motile cilia and flagella have nine outer doublet and two central pair (CP) microtubules. Outer doublet microtubules are continuous with the triplet microtubules of the basal body, are templated by the basal body microtubules, and grow by addition of new subunits to their distal (“plus”) ends. In contrast, CP microtubules are not continuous with basal body microtubules, raising the question of how these microtubules are assembled and how their polarity is established. Methods CP assembly in Chlamydomonas reinhardtii was analyzed by electron microscopy and wide-field and super-resolution immunofluorescence microscopy. To analyze CP assembly independently from flagellar assembly, the CP-deficient katanin mutants pf15 or pf19 were mated to wild-type cells. HA-tagged tubulin and the CP-specific protein hydin were used as markers to analyze de novo CP assembly inside the formerly mutant flagella. Results In regenerating flagella, the CP and its projections assemble near the transition zone soon after the onset of outer doublet elongation. During de novo CP assembly in full-length flagella, the nascent CP was first apparent in a subdistal region of the flagellum. The developing CP replaces a fibrous core that fills the axonemal lumen of CP-deficient flagella. The fibrous core contains proteins normally associated with the C1 CP microtubule and proteins involved in intraflagellar transport (IFT). In flagella of the radial spoke-deficient mutant pf14, two pairs of CPs are frequently present with identical correct polarities. Conclusions The temporal separation of flagellar and CP assembly in dikaryons formed by mating CP-deficient gametes to wild-type gametes revealed that the formation of the CP does not require proximity to the basal body or transition zone, or to the flagellar tip. The observations on pf14 provide further support that the CP self-assembles without a template and eliminate the possibility that CP polarity is established by interaction with axonemal radial spokes. Polarity of the developing CP may be determined by the proximal-to-distal gradient of precursor molecules. IFT proteins accumulate in flagella of CP mutants; the abnormal distribution of IFT proteins may explain why these flagella are often shorter than normal. PMID:24283352

Method of reducing multipole content in a conductor assembly during manufacture

DOEpatents

Meinke, Rainer [Melbourne, FL

2011-08-09

A method for manufacture of a conductor assembly. The assembly is of the type which, when conducting current, generates a magnetic field or in which, in the presence of a changing magnetic field, a voltage is induced. In an example embodiment one or more first coil rows are formed. The assembly has multiple coil rows about an axis with outer coil rows formed about inner coil rows. A determination is made of deviations from specifications associated with the formed one or more first coil rows. One or more deviations correspond to a magnitude of a multipole field component which departs from a field specification. Based on the deviations, one or more wiring patterns are generated for one or more second coil rows to be formed about the one or more first coil rows. The one or more second coil rows are formed in the assembly. The magnitude of each multipole field component that departs from the field specification is offset.

Method of reducing multipole content in a conductor assembly during manufacture

DOEpatents

Meinke, Rainer

2013-08-20

A method for manufacture of a conductor assembly. The assembly is of the type which, when conducting current, generates a magnetic field or in which, in the presence of a changing magnetic field, a voltage is induced. In an example embodiment one or more first coil rows are formed. The assembly has multiple coil rows about an axis with outer coil rows formed about inner coil rows. A determination is made of deviations from specifications associated with the formed one or more first coil rows. One or more deviations correspond to a magnitude of a multipole field component which departs from a field specification. Based on the deviations, one or more wiring patterns are generated for one or more second coil rows to be formed about the one or more first coil rows. The one or more second coil rows are formed in the assembly. The magnitude of each multipole field component that departs from the field specification is offset.

Combination radial and thrust magnetic bearing

NASA Technical Reports Server (NTRS)

Blumenstock, Kenneth A. (Inventor)

2002-01-01

A combination radial and thrust magnetic bearing is disclosed that allows for both radial and thrust axes control of an associated shaft. The combination radial and thrust magnetic bearing comprises a rotor and a stator. The rotor comprises a shaft, and first and second rotor pairs each having respective rotor elements. The stator comprises first and second stator elements and a magnet-sensor disk. In one embodiment, each stator element has a plurality of split-poles and a corresponding plurality of radial force coils and, in another embodiment, each stator element does not require thrust force coils, and radial force coils are replaced by double the plurality of coils serving as an outer member of each split-pole half.

Effect of asymmetrical eddy currents on magnetic diagnosis signals for equilibrium reconstruction in the Sino-UNIted Spherical Tokamak.

PubMed

Jiang, Y Z; Tan, Y; Gao, Z; Wang, L

2014-11-01

The vacuum vessel of Sino-UNIted Spherical Tokamak was split into two insulated hemispheres, both of which were insulated from the central cylinder. The eddy currents flowing in the vacuum vessel would become asymmetrical due to discontinuity. A 3D finite elements model was applied in order to study the eddy currents. The modeling results indicated that when the Poloidal Field (PF) was applied, the induced eddy currents would flow in the toroidal direction in the center of the hemispheres and would be forced to turn to the poloidal and radial directions due to the insulated slit. Since the eddy currents converged on the top and bottom of the vessel, the current densities there tended to be much higher than those in the equatorial plane were. Moreover, the eddy currents on the top and bottom of vacuum vessel had the same direction when the current flowed in the PF coils. These features resulted in the leading phases of signals on the top and bottom flux loops when compared with the PF waveforms.

Periprocedural safety of aneurysm embolization with the Medina Coil System: the early human experience.

PubMed

Turk, Aquilla S; Maia, Orlando; Ferreira, Christian Candido; Freitas, Diogo; Mocco, J; Hanel, Ricardo

2016-02-01

Intracranial saccular aneurysms, if untreated, carry a high risk of morbidity and mortality from intracranial bleeding. Embolization coils are the most common treatment. We describe the periprocedural safety and performance of the initial human experience with the next generation Medina Coil System. The Medina Coil System is a layered three-dimensional coil made from a radiopaque, shape set core wire, and shape memory alloy outer coil filaments. Nine aneurysms in five patients were selected for treatment with the Medina Coil System. Nine aneurysms in five patients, ranging from 5 to 17 mm in size in various locations, were treated with the Medina Coil System. No procedural or periprocedural complications were encountered. Procedure times, number of coils used to treat the aneurysm, and use of adjunctive devices were much less than anticipated if conventional coil technology had been used. The Medina Coil System is a next generation coil that combines all of the familiar and expected procedural safety and technique concepts associated with conventional coils. We found improved circumferential aneurysm filling, which may lead to improved long term outcomes, with fewer devices and faster operating times. 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/

Modelling controlled VDE's and ramp-down scenarios in ITER

NASA Astrophysics Data System (ADS)

Lodestro, L. L.; Kolesnikov, R. A.; Meyer, W. H.; Pearlstein, L. D.; Humphreys, D. A.; Walker, M. L.

2011-10-01

Following the design reviews of recent years, the ITER poloidal-field coil-set design, including in-vessel coils (VS3), and the divertor configuration have settled down. The divertor and its material composition (the latter has not been finalized) affect the development of fiducial equilibria and scenarios together with the coils through constraints on strike-point locations and limits on the PF and control systems. Previously we have reported on our studies simulating controlled vertical events in ITER with the JCT 2001 controller to which we added a PID VS3 circuit. In this paper we report and compare controlled VDE results using an optimized integrated VS and shape controller in the updated configuration. We also present our recent simulations of alternate ramp-down scenarios, looking at the effects of ramp-down time and shape strategies, using these controllers. This work performed under the auspices of the U.S. Department of Energy by LLNL under Contract DE-AC52-07NA27344.

Wettability of three Honduran bamboo species

Treesearch

X. B. Li; T.F. Shube; C.Y. Hse

2004-01-01

This study was initiated to determine the wettability of three Honduran bamboo species by contact-angiemeasurements. Static contact angles of urea formaldehyde (UF), phenol formaldehyde (PF), isocyanate (ISO) and distilled water on the bamboo surfaces were measured. The effects of bamboo species, layer (outer, middle and inner) and chemical treatment (hydrochloric acid...

Electromagnetic pump stator core

DOEpatents

Fanning, A.W.; Olich, E.E.; Dahl, L.R.

1995-01-17

A stator core for supporting an electrical coil includes a plurality of groups of circumferentially abutting flat laminations which collectively form a bore and perimeter. A plurality of wedges are interposed between the groups, with each wedge having an inner edge and a thicker outer edge. The wedge outer edges abut adjacent ones of the groups to provide a continuous path around the perimeter. 21 figures.

Electromagnetic pump stator core

DOEpatents

Fanning, Alan W.; Olich, Eugene E.; Dahl, Leslie R.

1995-01-01

A stator core for supporting an electrical coil includes a plurality of groups of circumferentially abutting flat laminations which collectively form a bore and perimeter. A plurality of wedges are interposed between the groups, with each wedge having an inner edge and a thicker outer edge. The wedge outer edges abut adjacent ones of the groups to provide a continuous path around the perimeter.

Chlamydomonas DYX1C1/PF23 is essential for axonemal assembly and proper morphology of inner dynein arms

PubMed Central

Yamamoto, Ryosuke; Alford, Lea M.; Ide, Takahiro; Owa, Mikito; Hwang, Juyeon; Inaba, Kazuo; James, Noliyanda; Ishikawa, Takashi

2017-01-01

Cytoplasmic assembly of ciliary dyneins, a process known as preassembly, requires numerous non-dynein proteins, but the identities and functions of these proteins are not fully elucidated. Here, we show that the classical Chlamydomonas motility mutant pf23 is defective in the Chlamydomonas homolog of DYX1C1. The pf23 mutant has a 494 bp deletion in the DYX1C1 gene and expresses a shorter DYX1C1 protein in the cytoplasm. Structural analyses, using cryo-ET, reveal that pf23 axonemes lack most of the inner dynein arms. Spectral counting confirms that DYX1C1 is essential for the assembly of the majority of ciliary inner dynein arms (IDA) as well as a fraction of the outer dynein arms (ODA). A C-terminal truncation of DYX1C1 shows a reduction in a subset of these ciliary IDAs. Sucrose gradients of cytoplasmic extracts show that preassembled ciliary dyneins are reduced compared to wild-type, which suggests an important role in dynein complex stability. The role of PF23/DYX1C1 remains unknown, but we suggest that DYX1C1 could provide a scaffold for macromolecular assembly. PMID:28892495

Design, simulation and testing of a novel radial multi-pole multi-layer magnetorheological brake

NASA Astrophysics Data System (ADS)

Wu, Jie; Li, Hua; Jiang, Xuezheng; Yao, Jin

2018-02-01

This paper deals with design, simulation and experimental testing of a novel radial multi-pole multi-layer magnetorheological (MR) brake. This MR brake has an innovative structural design with superposition principle of two magnetic fields generated by the inner coils and the outer coils. The MR brake has several media layers of magnetorheological (MR) fluid located between the inner coils and the outer coils, and it can provide higher torque and higher torque density than conventional single-disk or multi-disk or multi-pole single-layer MR brakes can. In this paper, a brief introduction to the structure of the proposed MR brake was given first. Then, theoretical analysis of the magnetic circuit and the braking torque was conducted. In addition, a 3D electromagnetic model of the MR brake was developed to simulate and examine the magnetic flux intensity and corresponding braking torque. A prototype of the brake was fabricated and several tests were carried out to validate its torque capacity. The results show that the proposed MR brake can produce a maximum braking torque of 133 N m and achieve a high torque density of 25.0 kN m-2, a high torque range of 42 and a high torque-to-power ratio of 0.95 N m W-1.

Control system for a small fission reactor

DOEpatents

Burelbach, James P.; Kann, William J.; Saiveau, James G.

1986-01-01

A system for controlling the reactivity of a small fission reactor includes an elongated, flexible hollow tube in the general form of a helical coiled spring axially positioned around and outside of the reactor vessel in an annular space between the reactor vessel and a surrounding cylindrical-shaped neutron reflector. A neutron absorbing material is provided within the hollow tube with the rate of the reaction controlled by the extension and compression of the hollow tube, e.g., extension of the tube increases reactivity while its compression reduces reactivity, in varying the amount of neutron absorbing material disposed between the reactor vessel and the neutron reflector. Conventional mechanical displacement means may be employed to control the coil density of the hollow tube as desired. In another embodiment, a plurality of flexible hollow tubes each containing a neutron absorber are positioned adjacent to one another in spaced relation around the periphery of the reactor vessel and inside the outer neutron reflector with reactivity controlled by the extension and compression of all or some of the coiled hollow tubes. Yet another embodiment of the invention envisions the neutron reflector in the form of an expandable coil spring positioned in an annular space between the reactor vessel and an outer neutron absorbing structure for controlling the neutron flux reflected back into the reactor vessel.

ELECTRON DISCHARGE DEVICE

DOEpatents

Graham, M.H.

1962-09-18

A barrier-grid storage tube and an improved means for writing and reading of information in such a tube are described. A triax cable is provided in the reading and writing circuit and includes a coiled portion. The inner conductor of the cable is connected to the back plate of the barrier grid target assembly of the storage tube, the middle conductor of the cable is connected to a shielding member encompassing the target assembly and this member supports the barrier grid of the assembly, and the outer conductor of the cable is connected to an external shreld surrounding the target assembly. A source of writing sr- gnals is connected between the rnner conductor and middle conductor of said cable. Both the middle and outer conductors are connected to ground at the source end, and a small trimmer condenser is connected between the external shield and the source end of the inner conductor of the cable to compensate for the direct back plate-to-ground capacity due to the imperfect shielding of the barrier grid. The coiled portion of the cable provides for an output signal to a secondary corl coupled thereto. The grounded outer conductor serves as a means for preventing an output signal being applied to the coiled portion of the cable on application of writing signals to the inner and middle conductors of the cable. (AEC)

Implementation of a transcutaneous charger for fully implantable middle ear hearing device.

PubMed

Lim, H; Yoon, Y; Lee, C; Park, I; Song, B; Cho, J

2005-01-01

A transcutaneous charger for the fully implantable middle ear hearing device (F-IMEHD), which can monitor the charging level of battery, has been designed and implemented. In order to recharge the battery of F-IMEHD, the electromagnetic coupling between primary coil at outer body and secondary coil at inner body has been used. Considering the implant condition of the F-IMEHD, the primary coil and the secondary coil have been designed. Using the resonance of LC tank circuit at each coil, transmission efficiency was increased. Since the primary and the secondary coil are magnetically coupled, the current variation of the primary coil is related with the impedance of internal resonant circuit. Using the principle mentioned above, the implanted module could transmit outward the information about charging state of battery or coupling between two coils by the changing internal impedance. As in the demonstrated results of experiment, the implemented charger has supplied the sufficient operating voltage for the implanted battery within about 10 mm distance. And also, it has been confirmed that the implanted module can transmit information outward by control of internal impedance.

Active combustion flow modulation valve

DOEpatents

Hensel, John Peter; Black, Nathaniel; Thorton, Jimmy Dean; Vipperman, Jeffrey Stuart; Lambeth, David N; Clark, William W

2013-09-24

A flow modulation valve has a slidably translating hollow armature with at least one energizable coil wound around and fixably attached to the hollow armature. The energizable coil or coils are influenced by at least one permanent magnet surrounding the hollow armature and supported by an outer casing. Lorentz forces on the energizable coils which are translated to the hollow armature, increase or decrease the flow area to provide flow throttling action. The extent of hollow armature translation depends on the value of current supplied and the direction of translation depends on the direction of current flow. The compact nature of the flow modulation valve combined with the high forces afforded by the actuator design provide a flow modulation valve which is highly responsive to high-rate input control signals.

Correction coil cable

DOEpatents

Wang, Sou-Tien

1994-11-01

A wire cable assembly (10, 310) adapted for the winding of electrical coils is taught. A primary intended use is for use in particle tube assemblies (532) for the superconducting super collider. The correction coil cables (10, 310) have wires (14, 314) collected in wire arrays (12, 312) with a center rib (16, 316) sandwiched therebetween to form a core assembly (18, 318 ). The core assembly (18, 318) is surrounded by an assembly housing (20, 320) having an inner spiral wrap (22, 322) and a counter wound outer spiral wrap (24, 324). An alternate embodiment (410) of the invention is rolled into a keystoned shape to improve radial alignment of the correction coil cable (410) on a particle tube (733) in a particle tube assembly (732).

Monocoil reciprocating permanent magnet electric machine with self-centering force

NASA Technical Reports Server (NTRS)

Bhate, Suresh K. (Inventor); Vitale, Nicholas G. (Inventor)

1989-01-01

A linear reciprocating machine has a tubular outer stator housing a coil, a plunger and an inner stator. The plunger has four axially spaced rings of radially magnetized permanent magnets which cooperate two at a time with the stator to complete first or second opposite magnetic paths. The four rings of magnets and the stators are arranged so that the stroke of the plunger is independent of the axial length of the coil.

Reciprocating linear motor

NASA Technical Reports Server (NTRS)

Goldowsky, Michael P. (Inventor)

1987-01-01

A reciprocating linear motor is formed with a pair of ring-shaped permanent magnets having opposite radial polarizations, held axially apart by a nonmagnetic yoke, which serves as an axially displaceable armature assembly. A pair of annularly wound coils having axial lengths which differ from the axial lengths of the permanent magnets are serially coupled together in mutual opposition and positioned with an outer cylindrical core in axial symmetry about the armature assembly. One embodiment includes a second pair of annularly wound coils serially coupled together in mutual opposition and an inner cylindrical core positioned in axial symmetry inside the armature radially opposite to the first pair of coils. Application of a potential difference across a serial connection of the two pairs of coils creates a current flow perpendicular to the magnetic field created by the armature magnets, thereby causing limited linear displacement of the magnets relative to the coils.

Multiphase soft switched DC/DC converter and active control technique for fuel cell ripple current elimination

DOEpatents

Lai, Jih-Sheng; Liu, Changrong; Ridenour, Amy

2009-04-14

DC/DC converter has a transformer having primary coils connected to an input side and secondary coils connected to an output side. Each primary coil connects a full-bridge circuit comprising two switches on two legs, the primary coil being connected between the switches on each leg, each full-bridge circuit being connected in parallel wherein each leg is disposed parallel to one another, and the secondary coils connected to a rectifying circuit. An outer loop control circuit that reduces ripple in a voltage reference has a first resistor connected in series with a second resistor connected in series with a first capacitor which are connected in parallel with a second capacitor. An inner loop control circuit that reduces ripple in a current reference has a third resistor connected in series with a fourth resistor connected in series with a third capacitor which are connected in parallel with a fourth capacitor.

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.

Heat Treatment Optimization of Rutherford Cables for a 15 T Nb 3Sn Dipole Demonstrator

DOE PAGES

Barzi, Emanuela; Bossert, Marianne; Field, Michael; ...

2017-01-09

FNAL has been developing a 15 T Nb 3Sn dipole demonstrator for a future Very High Energy pp Collider based on an optimized 60-mm aperture 4-layer “cos-theta” coil. In order to increase magnet efficiency, we graded the coil by using two cables with same 15 mm width and different thicknesses made of two different Restacked Rod Process (RRP®) wires. Due to the non-uniform field distribution in dipole coils the maximum field in the inner coil will reach 15-16 T, whereas the maximum field in the outer coil is 12-13 T. In preparation for the 15 T dipole coil reaction, heatmore » treatment studies were performed on strands extracted from these cables with the goal of achieving the best coil performance in the corresponding magnetic fields. Particularly, the effect of maximum temperature and time on the cable critical current was studied to take into account actual variations of these parameters during coil reaction. In parallel and in collaboration with OST, development was performed on optimizing Nb 3Sn RRP® wire design and layout. Index Terms— Accelerator magnet, critical current density, Nb 3Sn strand, Rutherford cable.« less

Induction magnetometer using a high-Tc superconductor coil

NASA Astrophysics Data System (ADS)

Sasada, Ichiro

2010-05-01

An induction magnetometer consisting of a search coil and an inverting operational amplifier is simple in structure and in signal transferring mechanism from the magnetic field input to the voltage output. Because this magnetometer is based on Faraday's law of induction, it has a lower cutoff frequency r/(2πL), where r is the resistance of the coil and L is its inductance. An attempt has been made to lower the cutoff frequency of the induction magnetometer by using a high-Tc superconductor coil. With a pancake coil (inner diameter ≈18 cm and outer diameter ≈23 cm, 92 turns, 3.23 mH) made of a Bismuth strontium calcium copper oxide (BSCCO) superconductor tape of 5 mm in width and 0.23 mm in thickness, the cutoff frequency achieved was 1.7 Hz which is much lower than that obtained with a bulky copper search coil which is typically in the range of 10-20 Hz. In the experiment, an inverting amplifier was made with a complementary metal-oxide semiconductor operational amplifier and was immersed in liquid nitrogen together with a BSCCO high-Tc superconducting coil. Discussion is made on the resolution of the induction magnetometer using a high-Tc superconductor search coil.

NASA superconducting magnetic mirror facility. [for thermonuclear research

NASA Technical Reports Server (NTRS)

Reinmann, J. J.; Swanson, M. C.; Nichols, C. R.; Bloy, S. J.; Nagy, L. A.; Brady, F. J.

1973-01-01

The design details and initial test results of a superconducting magnetic mirror facility that has been constructed at NASA Lewis Research Center for use in thermonuclear research are summarized. The magnet system consists of four solenoidal coils which are individually rated at 5.0 T. Each coll is composed of an inner, middle, and outer winding. The inner winding is wound of stabilized Nb3Sn superconducting ribbon, and the middle and outer windings are wound of stabilized Nb-Ti superconducting wire. When arranged in the mirror geometry, the four coils will produce 8.7 T at the mirrors and a 1.8 mirror ratio. The magnet has a 41-cm diameter clear bore which is open to atmosphere. Distance between the mirrors is 111 cm. Presently there are only three magnets in the facility; the fourth magnet is being rebuilt.

Toroidal midplane neutral beam armor and plasma limiter

DOEpatents

Kugel, Henry W.; Hand Jr, Samuel W.; Ksayian, Haig

1986-02-04

For use in a tokamak fusion reactor having a midplane magnetic coil on the inner wall of an evacuated toriodal chamber within which a neutral beam heated, fusing plasma is magnetically confined, a neutral beam armor shield and plasma limiter is provided on the inner wall of the toroidal chamber to shield the midplane coil from neutral beam shine-thru and plasma deposition. The armor shield/plasma limiter forms a semicircular enclosure around the midplane coil with the outer surface of the armor shield/plasma limiter shaped to match, as closely as practical, the inner limiting magnetic flux surface of the toroidally confined, indented, bean-shaped plasma. The armor shield/plasma limiter includes a plurality of semicircular graphite plates each having a pair of coupled upper and lower sections with each plate positioned in intimate contact with an adjacent plate on each side thereof so as to form a closed, planar structure around the entire outer periphery of the circular midplane coil. The upper and lower plate sections are adapted for coupling to heat sensing thermocouples and to a circulating water conduit system for cooling the armor shield/plasma limiter.The inner center portion of each graphite plate is adapted to receive and enclose a section of a circular diagnostic magnetic flux loop so as to minimize the power from the plasma confinement chamber incident upon the flux loop.

Toroidal midplane neutral beam armor and plasma limiter

DOEpatents

Kugel, Henry W.; Hand, Jr, Samuel W.; Ksayian, Haig

1986-01-01

For use in a tokamak fusion reactor having a midplane magnetic coil on the inner wall of an evacuated toriodal chamber within which a neutral beam heated, fusing plasma is magnetically confined, a neutral beam armor shield and plasma limiter is provided on the inner wall of the toroidal chamber to shield the midplane coil from neutral beam shine-thru and plasma deposition. The armor shield/plasma limiter forms a semicircular enclosure around the midplane coil with the outer surface of the armor shield/plasma limiter shaped to match, as closely as practical, the inner limiting magnetic flux surface of the toroidally confined, indented, bean-shaped plasma. The armor shield/plasma limiter includes a plurality of semicircular graphite plates each having a pair of coupled upper and lower sections with each plate positioned in intimate contact with an adjacent plate on each side thereof so as to form a closed, planar structure around the entire outer periphery of the circular midplane coil. The upper and lower plate sections are adapted for coupling to heat sensing thermocouples and to a circulating water conduit system for cooling the armor shield/plasma limiter.The inner center portion of each graphite plate is adapted to receive and enclose a section of a circular diagnostic magnetic flux loop so as to minimize the power from the plasma confinement chamber incident upon the flux loop.

Design of catheter radio frequency coils using coaxial transmission line resonators for interventional neurovascular MR imaging.

PubMed

Zhang, Xiaoliang; Martin, Alastair; Jordan, Caroline; Lillaney, Prasheel; Losey, Aaron; Pang, Yong; Hu, Jeffrey; Wilson, Mark; Cooke, Daniel; Hetts, Steven W

2017-04-01

It is technically challenging to design compact yet sensitive miniature catheter radio frequency (RF) coils for endovascular interventional MR imaging. In this work, a new design method for catheter RF coils is proposed based on the coaxial transmission line resonator (TLR) technique. Due to its distributed circuit, the TLR catheter coil does not need any lumped capacitors to support its resonance, which simplifies the practical design and construction and provides a straightforward technique for designing miniature catheter-mounted imaging coils that are appropriate for interventional neurovascular procedures. The outer conductor of the TLR serves as an RF shield, which prevents electromagnetic energy loss, and improves coil Q factors. It also minimizes interaction with surrounding tissues and signal losses along the catheter coil. To investigate the technique, a prototype catheter coil was built using the proposed coaxial TLR technique and evaluated with standard RF testing and measurement methods and MR imaging experiments. Numerical simulation was carried out to assess the RF electromagnetic field behavior of the proposed TLR catheter coil and the conventional lumped-element catheter coil. The proposed TLR catheter coil was successfully tuned to 64 MHz for proton imaging at 1.5 T. B 1 fields were numerically calculated, showing improved magnetic field intensity of the TLR catheter coil over the conventional lumped-element catheter coil. MR images were acquired from a dedicated vascular phantom using the TLR catheter coil and also the system body coil. The TLR catheter coil is able to provide a significant signal-to-noise ratio (SNR) increase (a factor of 200 to 300) over its imaging volume relative to the body coil. Catheter imaging RF coil design using the proposed coaxial TLR technique is feasible and advantageous in endovascular interventional MR imaging applications.

Manufacturing of REBCO coils strongly bonded to cooling members with epoxy resin aimed at its application to Maglev

NASA Astrophysics Data System (ADS)

Mizuno, Katsutoshi; Ogata, Masafumi; Hasegawa, Hitoshi

2014-11-01

The REBCO coated conductor has been attracted attention because of its high current density in the presence of high magnetic field. If the coated conductor is applied to Maglev, the operational temperature of the on-board magnets will be over 40 K and energy consumption of cryocoolers will be reduced. That high operational temperature also means the absence of liquid helium. Therefore, reliable thermal coupling is desirable for cooling the coils. We propose an epoxy impregnated REBCO coil co-wound with PTFE tape. While the PTFE tape prevents the performance degradation of the coil, the epoxy resin bonds the coil to cooling members. We carried out three experiments to confirm that the coil structure which we propose has robust thermal coupling without the degradation. First, thermal resistances of paraffin and epoxy were measured varying the temperature from room temperature to 10 K. The measurement result indicates that paraffin has a risk of losing thermal coupling during cooling down. In another experiment, PTFE (polytetrafluoroethylene) tape insulator prevented performance degradation of a small epoxy impregnated REBCO coil, while another REBCO coil with polyimide tape showed clear performance degradation. Finally, we produced a racetrack REBCO coil with the same outer dimension as a Maglev on-board magnet coil. Although the racetrack coil was installed in a GFRP coil case and tightly bonded to the case by epoxy impregnation, any performance degradation was not observed.

Refrigerated cryogenic envelope

DOEpatents

Loudon, John D.

1976-11-16

An elongated cryogenic envelope including an outer tube and an inner tube coaxially spaced within said inner tube so that the space therebetween forms a vacuum chamber for holding a vacuum. The inner and outer tubes are provided with means for expanding or contracting during thermal changes. A shield is located in the vacuum chamber intermediate the inner and outer tubes; and, a refrigeration tube for directing refrigeration to the shield is coiled about at least a portion of the inner tube within the vacuum chamber to permit the refrigeration tube to expand or contract along its length during thermal changes within said vacuum chamber.

Demonstration of Airborne Electromagnetic Systems for Detection and Characterization of Unexploded Ordnance at the Badlands Bombing Range, South Dakota. Revision 3

DTIC Science & Technology

2004-08-01

base station Attitude Measurement Ashtech ADU-2 Bartington MAG03ML7ONT 3-axis fluxgate magnetometer , Navigation Picodas PNAV100 Model P141-E Real...BBR Test Grid, horizontal difference (outer coil minus scaled inner coil). 46 22 Analytic signal derived from ground-based magnetometer bottom...one meter over UXO-contaminated terrain. As with the magnetic systems, GPS and laser altimetry provide precise positioning to within a few tens of

Concept of a Cryogenic System for a Cryogen-Free 25 T Superconducting Magnet

NASA Astrophysics Data System (ADS)

Iwai, Sadanori; Takahashi, Masahiko; Miyazaki, Hiroshi; Tosaka, Taizo; Tasaki, Kenji; Hanai, Satoshi; Ioka, Shigeru; Watanabe, Kazuo; Awaji, Satoshi; Oguro, Hidetoshi

A cryogen-free 25 T superconducting magnet using a ReBCO insert coil that generates 11.5 T in a 14 T background field of outer low-temperature superconducting (LTS) coils is currently under development. The AC loss of the insert coil during field ramping is approximately 8.8 W, which is difficult to dissipate at the operating temperature of the LTS coils (4 K). However, since a ReBCO coil can operate at a temperature above 4 K, the ReBCO insert coil is cooled to about 10 K by two GM cryocoolers, and the LTS coils are independently cooled by two GM/JT cryocoolers. Two GM cryocoolers cool a circulating helium gas through heat exchangers, and the gas is transported over a long distance to the cold stage located on the ReBCO insert coil, in order to protect the cryocoolers from the leakage field of high magnetic fields. The temperature difference of the 2nd cold stage of the GM cryocoolers and the insert coil can be reduced by increasing the gas flow rate. However, at the same time, the heat loss of the heat exchangers increases, and the temperature of the second cold stage is raised. Therefore, the gas flow rate is optimized to minimize the operating temperature of the ReBCO insert coil by using a flow controller and a bypass circuit connected to a buffer tank.

A polymer driveshaft for use in orbital and rotational atherectomy

NASA Astrophysics Data System (ADS)

Grothe, Preston Lee

Driveshafts used in atherectomy medical devices are often comprised of coiled or braided metal wires. These constructions are designed to tolerate delivery through tortuous vessels and can endure high speed rotation used during activation of the atherectomy treatment. This research investigated polymer driveshaft designs, which were comprised of polymer inner and outer layers, and coiled or braided stainless steel wires. The polymer driveshaft materials included polyimide, nylon 12, and polytetrafluoroethylene (PTFE). Mechanical testing of polymer driveshafts was conducted to determine material response in bending, tension, compression, and torsion. The polymer driveshaft test results were then compared with current coiled metal wire driveshaft constructions. The investigation identified polymer driveshaft options that could feasibly work in an atherectomy application.

Plasmodium falciparum coronin organizes arrays of parallel actin filaments potentially guiding directional motility in invasive malaria parasites.

PubMed

Olshina, Maya A; Angrisano, Fiona; Marapana, Danushka S; Riglar, David T; Bane, Kartik; Wong, Wilson; Catimel, Bruno; Yin, Meng-Xin; Holmes, Andrew B; Frischknecht, Friedrich; Kovar, David R; Baum, Jake

2015-07-18

Gliding motility in Plasmodium parasites, the aetiological agents of malaria disease, is mediated by an actomyosin motor anchored in the outer pellicle of the motile cell. Effective motility is dependent on a parasite myosin motor and turnover of dynamic parasite actin filaments. To date, however, the basis for directional motility is not known. Whilst myosin is very likely orientated as a result of its anchorage within the parasite, how actin filaments are orientated to facilitate directional force generation remains unexplained. In addition, recent evidence has questioned the linkage between actin filaments and secreted surface antigens leaving the way by which motor force is transmitted to the extracellular milieu unknown. Malaria parasites possess a markedly reduced repertoire of actin regulators, among which few are predicted to interact with filamentous (F)-actin directly. One of these, PF3D7_1251200, shows strong homology to the coronin family of actin-filament binding proteins, herein referred to as PfCoronin. Here the N terminal beta propeller domain of PfCoronin (PfCor-N) was expressed to assess its ability to bind and bundle pre-formed actin filaments by sedimentation assay, total internal reflection fluorescence (TIRF) microscopy and confocal imaging as well as to explore its ability to bind phospholipids. In parallel a tagged PfCoronin line in Plasmodium falciparum was generated to determine the cellular localization of the protein during asexual parasite development and blood-stage merozoite invasion. A combination of biochemical approaches demonstrated that the N-terminal beta-propeller domain of PfCoronin is capable of binding F-actin and facilitating formation of parallel filament bundles. In parasites, PfCoronin is expressed late in the asexual lifecycle and localizes to the pellicle region of invasive merozoites before and during erythrocyte entry. PfCoronin also associates strongly with membranes within the cell, likely mediated by interactions with phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) at the plasma membrane. These data suggest PfCoronin may fulfil a key role as the critical determinant of actin filament organization in the Plasmodium cell. This raises the possibility that macro-molecular organization of actin mediates directional motility in gliding parasites.

Design, fabrication and characterization of LTCC-based electromagnetic microgenerators

NASA Astrophysics Data System (ADS)

Gierczak, M.; Markowski, P.; Dziedzic, A.

2016-02-01

Design, manufacturing process and properties of electromagnetic microgenerators fabricated in LTCC (Low Temperature Co-fired Ceramics) technology are presented in this paper. Electromagnetic microgenerators consist of planar coils spatially arranged on several layers of LTCC and of a multipole permanent magnet. Two different patterns of coils with 2-, 8-,10- and 12-layers and outer diameter of 50 mm were designed and fabricated. Silver-based pastes ESL 903-A or DuPont 6145 were used. In order to estimate the inductance of a single spatial coil the Greenhouse (self-inductance) and Hoer (mutual inductance) calculation methods were used. To verify the calculation results a single-layer coil was fabricated for each pattern and its inductance was measured using the precision RLC Meter. Fabricated LTCC microgenerators with embedded coils allow to generate voltage higher than ten volts and the electrical output power of approximately 600 mW at the rotor rotation speed of 12 thousands rpm. The self-made system was used for characterization of LTCC-based electromagnetic microgenerators.

Design Features and Commissioning of the Versatile Experiment Spherical Torus (VEST) at Seoul National University

NASA Astrophysics Data System (ADS)

J. Chung, K.; H. An, Y.; K. Jung, B.; Y. Lee, H.; C., Sung; S. Na, Y.; S. Hahm, T.; S. Hwang, Y.

2013-03-01

A new spherical torus called VEST (Versatile Experiment Spherical Torus) is designed, constructed and successfully commissioned at Seoul National University. A unique design feature of the VEST is two partial solenoid coils installed at both vertical ends of a center stack, which can provide sufficient magnetic fluxes to initiate tokamak plasmas while keeping a low aspect ratio configuration in the central region. According to initial double null merging start-up scenario using the partial solenoid coils, appropriate power supplies for driving a toroidal field coil, outer poloidal field coils, and the partial solenoid coils are fabricated and successfully commissioned. For reliable start-up, a pre-ionization system with two cost-effective homemade magnetron power supplies is also prepared. In addition, magnetic and spectroscopic diagnostics with appropriate data acquisition and control systems are well prepared for initial operation of the device. The VEST is ready for tokamak plasma operation by completing and commissioning most of the designed components.

Location dependent coordination chemistry and MRI relaxivity, in de novo designed lanthanide coiled coils† †Electronic supplementary information (ESI) available: Methods, peptide characterization data including mass spectrometry and analytical HPLC, sedimentation equilibrium data, circular dichroism, luminescence, and NMR data. See DOI: 10.1039/c5sc04101e

PubMed Central

Berwick, Matthew R.; Slope, Louise N.; Smith, Caitlin F.; King, Siobhan M.; Newton, Sarah L.; Gillis, Richard B.; Adams, Gary G.; Rowe, Arthur J.; Harding, Stephen E.; Britton, Melanie M.

2016-01-01

Herein, we establish for the first time the design principles for lanthanide coordination within coiled coils, and the important consequences of binding site translation. By interrogating design requirements and by systematically translating binding site residues, one can influence coiled coil stability and more importantly, the lanthanide coordination chemistry. A 10 Å binding site translation along a coiled coil, transforms a coordinatively saturated Tb(Asp)3(Asn)3 site into one in which three exogenous water molecules are coordinated, and in which the Asn layer is no longer essential for binding, Tb(Asp)3(H2O)3. This has a profound impact on the relaxivity of the analogous Gd(iii) coiled coil, with more than a four-fold increase in the transverse relaxivity (21 to 89 mM–1 s–1), by bringing into play, in addition to the outer sphere mechanism present for all Gd(iii) coiled coils, an inner sphere mechanism. Not only do these findings warrant further investigation for possible exploitation as MRI contrast agents, but understanding the impact of binding site translation on coordination chemistry has important repercussions for metal binding site design, taking us an important step closer to the predictable and truly de novo design of metal binding sites, for new functional applications. PMID:29899946

Three-axis force actuator for a magnetic bearing

NASA Technical Reports Server (NTRS)

Gondhalekar, Vijay (Inventor)

1998-01-01

This invention features a three-axis force actuator that axially, radially and rotatably supports a bearing member for frictionless rotation about an axis of rotation generally coincident with a Z-axis. Also featured is a magnetic bearing having such an actuator. The actuator includes an inner member, a magnetic member and a pole assembly having a ring member and four pole extending therefrom. The poles are equi-angular spaced from each other and radially spaced about the Z-axis. The inner member extends along the Z-axis and is a highly magnetic permeable material. The magnetic member is formed about the inner member outer surface, extends along the Z-axis and is configured so one magnetic pole polarity is located at its outer surface and the other polarity pole is located at its inner surface. Preferably, the magnetic member is a radially magnetized permanent magnet. The inner surface of the ring member is magnetically coupled to the magnetic member and a face of each pole is coupled to the bearing member. The magnetic member, the pole assembly, the inner member and the bearing member cooperate to generate a magnetic field that radially and rotatably supports a rotating member secured to the bearing member. The actuator further includes a plurality of electromagnetic coils. Preferably, a coil is formed about each pole and at least 2 coils are formed about the inner member. When energized, the electromagnetic coils generate a modulated magnetic field that stabilizes the rotating member in the desired operational position.

Magnetic Compression Experiment at General Fusion with Simulation Results

NASA Astrophysics Data System (ADS)

Dunlea, Carl; Khalzov, Ivan; Hirose, Akira; Xiao, Chijin; Fusion Team, General

2017-10-01

The magnetic compression experiment at GF was a repetitive non-destructive test to study plasma physics applicable to Magnetic Target Fusion compression. A spheromak compact torus (CT) is formed with a co-axial gun into a containment region with an hour-glass shaped inner flux conserver, and an insulating outer wall. External coil currents keep the CT off the outer wall (levitation) and then rapidly compress it inwards. The optimal external coil configuration greatly improved both the levitated CT lifetime and the rate of shots with good compressional flux conservation. As confirmed by spectrometer data, the improved levitation field profile reduced plasma impurity levels by suppressing the interaction between plasma and the insulating outer wall during the formation process. We developed an energy and toroidal flux conserving finite element axisymmetric MHD code to study CT formation and compression. The Braginskii MHD equations with anisotropic heat conduction were implemented. To simulate plasma / insulating wall interaction, we couple the vacuum field solution in the insulating region to the full MHD solution in the remainder of the domain. We see good agreement between simulation and experiment results. Partly funded by NSERC and MITACS Accelerate.

The FapF amyloid secretion transporter possesses an atypical asymmetric coiled coil.

PubMed

Rouse, Sarah L; Stylianou, Fisentzos; Grace Wu, H Y; Berry, Jamie-Lee; Sewell, Lee; Morgan, R Marc L; Sauerwein, Andrea C; Matthews, Steve

2018-06-07

Gram-negative bacteria possess specialised biogenesis machineries that facilitate the export of amyloid subunits, the fibres of which are key components of their biofilm matrix. The secretion of bacterial functional amyloid requires a specialised outer-membrane protein channel through which unfolded amyloid substrates are translocated. We previously reported the crystal structure of the membrane-spanning domain of the amyloid subunit transporter FapF from Pseudomonas. However, the structure of the periplasmic domain, which is essential for amyloid transport, is yet to be determined. Here, we present the crystal structure of the N-terminal periplasmic domain at 1.8 Å resolution. This domain forms a novel asymmetric trimeric coiled-coil that possesses a single buried tyrosine residue as well as a extensive hydrogen-bonding network within a glutamine layer. This new structural insight allows us to understand this newly described functional amyloid secretion system in greater detail. Copyright © 2018. Published by Elsevier Ltd.

Operation of a 400MHz NMR magnet using a (RE:Rare Earth)Ba2Cu3O7-x high-temperature superconducting coil: Towards an ultra-compact super-high field NMR spectrometer operated beyond 1GHz.

PubMed

Yanagisawa, Y; Piao, R; Iguchi, S; Nakagome, H; Takao, T; Kominato, K; Hamada, M; Matsumoto, S; Suematsu, H; Jin, X; Takahashi, M; Yamazaki, T; Maeda, H

2014-12-01

High-temperature superconductors (HTS) are the key technology to achieve super-high magnetic field nuclear magnetic resonance (NMR) spectrometers with an operating frequency far beyond 1GHz (23.5T). (RE)Ba 2 Cu 3 O 7- x (REBCO, RE: rare earth) conductors have an advantage over Bi 2 Sr 2 Ca 2 Cu 3 O 10- x (Bi-2223) and Bi 2 Sr 2 CaCu 2 O 8- x (Bi-2212) conductors in that they have very high tensile strengths and tolerate strong electromagnetic hoop stress, thereby having the potential to act as an ultra-compact super-high field NMR magnet. As a first step, we developed the world's first NMR magnet comprising an inner REBCO coil and outer low-temperature superconducting (LTS) coils. The magnet was successfully charged without degradation and mainly operated at 400MHz (9.39T). Technical problems for the NMR magnet due to screening current in the REBCO coil were clarified and solved as follows: (i) A remarkable temporal drift of the central magnetic field was suppressed by a current sweep reversal method utilizing ∼10% of the peak current. (ii) A Z2 field error harmonic of the main coil cannot be compensated by an outer correction coil and therefore an additional ferromagnetic shim was used. (iii) Large tesseral harmonics emerged that could not be corrected by cryoshim coils. Due to those harmonics, the resolution and sensitivity of NMR spectra are ten-fold lower than those for a conventional LTS NMR magnet. As a result, a HSQC spectrum could be achieved for a protein sample, while a NOESY spectrum could not be obtained. An ultra-compact 1.2GHz NMR magnet could be realized if we effectively take advantage of REBCO conductors, although this will require further research to suppress the effect of the screening current. Copyright © 2014 Elsevier Inc. All rights reserved.

Submersible sodium pump

DOEpatents

Brynsvold, Glen V.; Lopez, John T.; Olich, Eugene E.; West, Calvin W.

1989-01-01

An electromagnetic submerged pump has an outer cylindrical stator with an inner cylindrical conductive core for the submerged pumping of sodium in the cylindrical interstitial volume defined between the stator and core. The cylindrical interstitial volume is typically vertically oriented, and defines an inlet at the bottom and an outlet at the top. The outer stator generates upwardly conveyed toroidal magnetic fields, which fields convey preferably from the bottom of the pump to the top of the pump liquid sodium in the cold leg of a sodium cooled nuclear reactor. The outer cylindrical stator has a vertically disposed duct surrounded by alternately stacked layers of coil units and laminates.

Submersible sodium pump

DOEpatents

Brynsvold, G.V.; Lopez, J.T.; Olich, E.E.; West, C.W.

1989-11-21

An electromagnetic submerged pump has an outer cylindrical stator with an inner cylindrical conductive core for the submerged pumping of sodium in the cylindrical interstitial volume defined between the stator and core. The cylindrical interstitial volume is typically vertically oriented, and defines an inlet at the bottom and an outlet at the top. The outer stator generates upwardly conveyed toroidal magnetic fields, which fields convey preferably from the bottom of the pump to the top of the pump liquid sodium in the cold leg of a sodium cooled nuclear reactor. The outer cylindrical stator has a vertically disposed duct surrounded by alternately stacked layers of coil units and laminates. 14 figs.

Advancements in Theoretical Models of Confined Vortex Flowfields

DTIC Science & Technology

2007-03-29

blades, curved vanes, vortex generators, twisted tape inserts, triangular winglets , propellers, coiled wires, tangential injectors, and other...Corresponding boundary conditions consist of the no slip at the wall and blending with the composite inner solution in the outer domain. Following similar

Ti film deposition process of a plasma focus: Study by an experimental design

NASA Astrophysics Data System (ADS)

Inestrosa-Izurieta, M. J.; Moreno, J.; Davis, S.; Soto, L.

2017-10-01

The plasma generated by plasma focus (PF) devices have substantially different physical characteristics from another plasma, energetic ions and electrons, compared with conventional plasma devices used for plasma nanofabrication, offering new and unique opportunities in the processing and synthesis of Nanomaterials. This article presents the use of a plasma focus of tens of joules, PF-50J, for the deposition of materials sprayed from the anode by the plasma dynamics in the axial direction. This work focuses on the determination of the most significant effects of the technological parameters of the system on the obtained depositions through the use of a statistical experimental design. The results allow us to give a qualitative understanding of the Ti film deposition process in our PF device depending on four different events provoked by the plasma dynamics: i) an electric erosion of the outer material of the anode; ii) substrate ablation generating an interlayer; iii) electron beam deposition of material from the center of the anode; iv) heat load provoking clustering or even melting of the deposition surface.

Results of availability imposed configuration details developed for K-DEMO

DOE PAGES

Brown, Tom; Titus, Peter; Brooks, Art; ...

2016-02-05

We completed a two year study using the Korean fusion demonstration reactor (K-DEMO) where we looked at key Tokamak components and configuration options in preparation of a conceptual design phase. A key part of a device configuration centers on defining an arrangement that enhances the ability to reach high availability values by defining design solutions that foster simplified maintenance operations. In order to maximize the size and minimize the number of in-vessel components enlarged TF coils were defined that incorporate a pair of windings within each coil to mitigate pressure drop issues and to reduce the cost of the coils.more » Furthermore, we defined a semi-permanent shield structure in order to develop labyrinth interfaces between double-null plasma contoured shield modules, provide an entity to align blanket components and provide support against disruption loads—with a load path that equilibrates blanket, TF and PF loads through a base structure. Blanket piping services and auxiliary systems that interface with in-vessel components have played a major role in defining the overall device arrangement—concept details will be presented along with general arrangement features and preliminary results obtained from disruption analysis.« less

Construction and Evaluation of Rodent-Specific rTMS Coils.

PubMed

Tang, Alexander D; Lowe, Andrea S; Garrett, Andrew R; Woodward, Robert; Bennett, William; Canty, Alison J; Garry, Michael I; Hinder, Mark R; Summers, Jeffery J; Gersner, Roman; Rotenberg, Alexander; Thickbroom, Gary; Walton, Joseph; Rodger, Jennifer

2016-01-01

Rodent models of transcranial magnetic stimulation (TMS) play a crucial role in aiding the understanding of the cellular and molecular mechanisms underlying TMS induced plasticity. Rodent-specific TMS have previously been used to deliver focal stimulation at the cost of stimulus intensity (12 mT). Here we describe two novel TMS coils designed to deliver repetitive TMS (rTMS) at greater stimulation intensities whilst maintaining spatial resolution. Two circular coils (8 mm outer diameter) were constructed with either an air or pure iron-core. Peak magnetic field strength for the air and iron-cores were 90 and 120 mT, respectively, with the iron-core coil exhibiting less focality. Coil temperature and magnetic field stability for the two coils undergoing rTMS, were similar at 1 Hz but varied at 10 Hz. Finite element modeling of 10 Hz rTMS with the iron-core in a simplified rat brain model suggests a peak electric field of 85 and 12.7 V/m, within the skull and the brain, respectively. Delivering 10 Hz rTMS to the motor cortex of anaesthetized rats with the iron-core coil significantly increased motor evoked potential amplitudes immediately after stimulation (n = 4). Our results suggest these novel coils generate modest magnetic and electric fields, capable of altering cortical excitability and provide an alternative method to investigate the mechanisms underlying rTMS-induced plasticity in an experimental setting.

Electromagnetic flat sheet forming by spiral type actuator coil

NASA Astrophysics Data System (ADS)

Akbar, S.; Aleem, M. A.; Sarwar, M. N.; Zillohu, A. U.; Awan, M. S.; Haider, A.; Ahmad, Z.; Akhtar, S.; Farooque, M.

2016-08-01

Focus of present work is to develop a setup for high strain rate electromagnetic forming of thin aluminum sheets (0.5, 1.0, 1.5 and 2.0 mm) and optimization of forming parameters. Flat spiral coil of 99.9% pure Cu strip (2.5x8.0 mm) with self-inductance 11 μH, 13 no. of turns and resultant outer diameter of 130mm has been fabricated and was coupled to a capacitor bank of energy, voltage and capacitance of 9 kJ, 900 V and 22.8 mF, respectively. To optimize the coil design, a commercially available software FEMM-4.2 was used to simulate the electromagnetic field profile generated by the coils of different pitch but same number of turns. Results of electromagnetic field intensity proposed by simulation agree in close proximity with those of theoretical as well as experimental data. The calculation of electromagnetic force and magnetic couplings between the coil and metal sheet are made. Forming parameters were optimized for different sheet thicknesses. Electromagnetic field intensity's profile plays a principal role in forming of typical shapes and patterns in sheets.

Echo-Planar Imaging for a 9.4 Tesla Vertical-Bore Superconducting Magnet Using an Unshielded Gradient Coil.

PubMed

Kodama, Nao; Kose, Katsumi

2016-10-11

Echo-planar imaging (EPI) sequences were developed for a 9.4 Tesla vertical standard bore (~54 mm) superconducting magnet using an unshielded gradient coil optimized for live mice imaging and a data correction technique with reference scans. Because EPI requires fast switching of intense magnetic field gradients, eddy currents were induced in the surrounding metallic materials, e.g., the room temperature bore, and this produced serious artifacts on the EPI images. We solved the problem using an unshielded gradient coil set of proper size (outer diameter = 39 mm, inner diameter = 32 mm) with time control of the current rise and reference scans. The obtained EPI images of a phantom and a plant sample were almost artifact-free and demonstrated the promise of our approach.

Control of the Helicity Content of a Gun-Generated Spheromak by Incorporating a Conducting Shell into a Magnetized Coaxial Plasma Gun

NASA Astrophysics Data System (ADS)

Matsumoto, Tadafumi; Sekiguchi, Jun'ichi; Asai, Tomohiko

In the formation of magnetized plasmoid by a magnetized coaxial plasma gun (MCPG), the magnetic helicity content of the generated plasmoid is one of the critical parameters. Typically, the bias coil to generate a poloidal flux is mounted either on the outer electrode or inside the inner electrode. However, most of the flux generated in the conventional method spreads even radially outside of the formation region. Thus, only a fraction of the total magnetic flux is actually exploited for helicity generation in the plasmoid. In the proposed system, the plasma gun incorporates a copper shell mounted on the outer electrode. By changing the rise time of the discharge bias coil current and the geometrical structure of the shell, the magnetic field structure and its time evolution can be controlled. The effect of the copper shell has been numerically simulated for the actual gun structure, and experimentally confirmed. This may increase the magnetic helicity content results, through increased poloidal magnetic field.

Enhanced heat transfer with full circumferential ribs in helical pipe

NASA Astrophysics Data System (ADS)

Chang, S. W.; Su, L. M.; Yang, T. L.

2002-08-01

This paper describes an experimental study of heat transfers in the smooth-walled and rib-roughened helical pipes with reference to the design of enhanced cooling passages in the cylinder head and liner of a marine propulsive diesel engine. The manner in which the repeated ribs modify the forced heat convection in the helical pipe is considered for the case where the flow is turbulent upon entering the coil but laminar in further downstream. A selection of experimental results illustrates the individual and interactive effects of Dean vortices and rib-flows on heat transfer along the inner and outer helixes of coils. The experimental-based observations reveal that the centrifugal force modifies the heat transfer in a manner to generate circumferential heat transfer variation with better cooling performance on the outer edge relative to its inner counterpart even with the agitated flow field caused by the repeated ribs. Heat transfer augmentation factor in the range of 1.3 - 3 times of the smooth-walled level is achieved using the present ribbing geometry. A set of empirical correlations based on the experimental data has been developed to permit the evaluation of heat transfers along the inner and outer helixes of the smooth-walled and rib-roughened helical pipes.

Quartz antenna with hollow conductor

DOEpatents

Leung, Ka-Ngo; Benabou, Elie

2002-01-01

A radio frequency (RF) antenna for plasma ion sources is formed of a hollow metal conductor tube disposed within a glass tube. The hollow metal tubular conductor has an internal flow channel so that there will be no coolant leakage if the outer glass tube of the antenna breaks. A portion of the RF antenna is formed into a coil; the antenna is used for inductively coupling RF power to a plasma in an ion source chamber. The antenna is made by first inserting the metal tube inside the glass tube, and then forming the glass/metal composite tube into the desired coil shape.

Magnetic induction spectroscopy (MIS)-probe design for cervical tissue measurements.

PubMed

Wang, Jau-Yi; Healey, Timothy; Barker, Anthony; Brown, Brian; Monk, Chris; Anumba, Dilly

2017-05-01

Gradiometers have the advantage of increasing measuring sensitivity, which is particularly useful in magnetic induction spectroscopy (MIS) for bio-impedance measurements. Traditional gradiometers use a pair of field sensing coils equally distant and on opposite sides of a drive coil, which provides high immunity to interference. In this paper, a ferrite-cored coaxial gradiometer probe of 29 mm diameter has been developed for measuring the impedance spectra of cervical tissues in vivo. It consists of a ferrite rod with outer ferrite confinement screening in order to eliminate the signals from surrounding tissue. The magnetic screening efficiency was compared with an air-cored gradiometer probe. For both gradiometer probes, a drive coil and two sensing coils were wound on a borosilicate glass former aligned coaxially with two sensing coils equidistant from the drive coil. The signal sensitivity of those two MIS gradiometers has been measured using saline samples with a conductivity range between 0.1 and 1.1 S m -1 . Finite element methods using COMSOL Multiphysics have been used to simulate the distribution of sensitivity to conductivity over the face of each probe and with depth. The ferrite-cored probe has a sensitivity confined to the volume defined by the gap between the ferrite core and outer tube of ferrite while the air-cored probe without any magnetic shielding had a wide sensitivity over the face and the side of the probe. Four saline samples and one of distilled water with conductivities from 0.1 to 1.1 S m -1 have been used to make conductivity measurements at frequencies of 50 kHz, 100 kHz, and 300 kHz. The measurement accuracy of the air-cored MIS probe was 0.09 S m -1 at 50 kHz, improving to 0.05 S m -1 at 300 kHz. For the ferrite-cored MIS probe, the measurement accuracy was 0.28 S m -1 at 50 kHz, improving to 0.04 S m -1 at 300 kHz. In vivo measurements on human hand have been performed using both types of gradiometers and the conductivity is consistent with reported data.

Internal position and limit sensor for free piston machines

NASA Technical Reports Server (NTRS)

Holliday, Ezekiel S. (Inventor); Wood, James Gary (Inventor)

2012-01-01

A sensor for sensing the position of a reciprocating free piston in a free piston Stirling machine. The sensor has a disk mounted to an end face of the power piston coaxially with its cylinder and reciprocating with the piston The disk includes a rim around its outer perimeter formed of an electrically conductive material A coil is wound coaxially with the cylinder, spaced outwardly from the outer perimeter of the disk and mounted in fixed position relative to the pressure vessel, preferably on the exterior of the pressure vessel wall.

Mechanical Properties of High Manganese Austenitic Stainless Steel JK2LB for ITER Central Solenoid Jacket Material

NASA Astrophysics Data System (ADS)

Saito, Toru; Kawano, Katsumi; Yamazaki, Toru; Ozeki, Hidemasa; Isono, Takaaki; Hamada, Kazuya; Devred, Arnaud; Vostner, Alexander

A suite of advanced austenitic stainless steels are used for the ITER TF, CS and PF coil systems.These materials will be exposed to cyclic-stress at cryogenic temperature. Therefore, high manganese austenitic stainless steel JK2LB, which has high tensile strength, high ductility and high resistance to fatigue at 4 K has been chosen for the CS conductor. The cryogenic temperature mechanical property data of this material are very important for the ITER magnet design. This study is focused on mechanical characteristics of JK2LB and its weld joint.

MRI surface-coil pair with strong inductive coupling.

PubMed

Mett, Richard R; Sidabras, Jason W; Hyde, James S

2016-12-01

A novel inductively coupled coil pair was used to obtain magnetic resonance phantom images. Rationale for using such a structure is described in R. R. Mett et al. [Rev. Sci. Instrum. 87, 084703 (2016)]. The original rationale was to increase the Q-value of a small diameter surface coil in order to achieve dominant loading by the sample. A significant improvement in the vector reception field (VRF) is also seen. The coil assembly consists of a 3-turn 10 mm tall meta-metallic self-resonant spiral (SRS) of inner diameter 10.4 mm and outer diameter 15.1 mm and a single-loop equalization coil of 25 mm diameter and 2 mm tall. The low-frequency parallel mode was used in which the rf currents on each coil produce magnetic fields that add constructively. The SRS coil assembly was fabricated and data were collected using a tissue-equivalent 30% polyacrylamide phantom. The large inductive coupling of the coils produces phase-coherency of the rf currents and magnetic fields. Finite-element simulations indicate that the VRF of the coil pair is about 4.4 times larger than for a single-loop coil of 15 mm diameter. The mutual coupling between coils influences the current ratio between the coils, which in turn influences the VRF and the signal-to-noise ratio (SNR). Data on a tissue-equivalent phantom at 9.4 T show a total SNR increase of 8.8 over the 15 mm loop averaged over a 25 mm depth and diameter. The experimental results are shown to be consistent with the magnetic resonance theory of the emf induced by spins in a coil, the theory of inductively coupled resonant circuits, and the superposition principle. The methods are general for magnetic resonance and other types of signal detection and can be used over a wide range of operating frequencies.

Water permeability of the mammalian cochlea: functional features of an aquaporin-facilitated water shunt at the perilymph-endolymph barrier.

PubMed

Eckhard, A; Müller, M; Salt, A; Smolders, J; Rask-Andersen, H; Löwenheim, H

2014-10-01

The cochlear duct epithelium (CDE) constitutes a tight barrier that effectively separates the inner ear fluids, endolymph and perilymph, thereby maintaining distinct ionic and osmotic gradients that are essential for auditory function. However, in vivo experiments have demonstrated that the CDE allows for rapid water exchange between fluid compartments. The molecular mechanism governing water permeation across the CDE remains elusive. We computationally determined the diffusional (PD) and osmotic (Pf) water permeability coefficients for the mammalian CDE based on in silico simulations of cochlear water dynamics integrating previously derived in vivo experimental data on fluid flow with expression sites of molecular water channels (aquaporins, AQPs). The PD of the entire CDE (PD = 8.18 × 10(-5) cm s(-1)) and its individual partitions including Reissner's membrane (PD = 12.06 × 10(-5) cm s(-1)) and the organ of Corti (PD = 10.2 × 10(-5) cm s(-1)) were similar to other epithelia with AQP-facilitated water permeation. The Pf of the CDE (Pf = 6.15 × 10(-4) cm s(-1)) was also in the range of other epithelia while an exceptionally high Pf was determined for an epithelial subdomain of outer sulcus cells in the cochlear apex co-expressing AQP4 and AQP5 (OSCs; Pf = 156.90 × 10(-3) cm s(-1)). The Pf/PD ratios of the CDE (Pf/PD = 7.52) and OSCs (Pf/PD = 242.02) indicate an aqueous pore-facilitated water exchange and reveal a high-transfer region or "water shunt" in the cochlear apex. This "water shunt" explains experimentally determined phenomena of endolymphatic longitudinal flow towards the cochlear apex. The water permeability coefficients of the CDE emphasise the physiological and pathophysiological relevance of water dynamics in the cochlea in particular for endolymphatic hydrops and Ménière's disease.

Echo-Planar Imaging for a 9.4 Tesla Vertical-Bore Superconducting Magnet Using an Unshielded Gradient Coil

PubMed Central

KODAMA, Nao; KOSE, Katsumi

2016-01-01

Echo-planar imaging (EPI) sequences were developed for a 9.4 Tesla vertical standard bore (∼54 mm) superconducting magnet using an unshielded gradient coil optimized for live mice imaging and a data correction technique with reference scans. Because EPI requires fast switching of intense magnetic field gradients, eddy currents were induced in the surrounding metallic materials, e.g., the room temperature bore, and this produced serious artifacts on the EPI images. We solved the problem using an unshielded gradient coil set of proper size (outer diameter = 39 mm, inner diameter = 32 mm) with time control of the current rise and reference scans. The obtained EPI images of a phantom and a plant sample were almost artifact-free and demonstrated the promise of our approach. PMID:27001398

Magnetoresistive flux focusing eddy current flaw detection

NASA Technical Reports Server (NTRS)

Wincheski, Russell A. (Inventor); Simpson, John W. (Inventor); Namkung, Min (Inventor)

2005-01-01

A giant magnetoresistive flux focusing eddy current device effectively detects deep flaws in thick multilayer conductive materials. The probe uses an excitation coil to induce eddy currents in conducting material perpendicularly oriented to the coil's longitudinal axis. A giant magnetoresistive (GMR) sensor, surrounded by the excitation coil, is used to detect generated fields. Between the excitation coil and GMR sensor is a highly permeable flux focusing lens which magnetically separates the GMR sensor and excitation coil and produces high flux density at the outer edge of the GMR sensor. The use of feedback inside the flux focusing lens enables complete cancellation of the leakage fields at the GMR sensor location and biasing of the GMR sensor to a location of high magnetic field sensitivity. In an alternate embodiment, a permanent magnet is positioned adjacent to the GMR sensor to accomplish the biasing. Experimental results have demonstrated identification of flaws up to 1 cm deep in aluminum alloy structures. To detect deep flaws about circular fasteners or inhomogeneities in thick multilayer conductive materials, the device is mounted in a hand-held rotating probe assembly that is connected to a computer for system control, data acquisition, processing and storage.

Design of a Long-Stroke Noncontact Electromagnetic Actuator for Active Vibration Isolation

NASA Technical Reports Server (NTRS)

Banerjee, Bibhuti; Allaire, Paul E.

1996-01-01

A long-stroke moving coil Lorentz Actuator was designed for use in a microgravity vibration isolation experiment. The final design had a stroke of 5.08 cm (2 in) and enough force capability to isolate a mass of the order of 22.7-45.4 kg. A simple dynamic magnetic circuit analysis, using an electrical analog, was developed for the initial design of the actuator. A neodymium-iron-boron material with energy density of 278 T-kA/m (35 MGOe) was selected to supply the magnetic field. The effect of changes in the design parameters of core diameter, shell outer diameter, pole face length, and coil wire layers were investigated. An extensive three-dimensional finite element analysis was carried out to accurately determine linearity with regard to axial position of the coil and coil current levels. The actuator was constructed and tested on a universal testing machine. Example plots are shown, indicating good linearity over the stroke of approximately 5.08 cm (2 in) and a range of coil currents from -1.5 A to +1.5 A. The actuator was then used for the microgravity vibration isolation experiments, described elsewhere.

Magnetoresistive Flux Focusing Eddy Current Flaw Detection

NASA Technical Reports Server (NTRS)

Wincheski, Russell A. (Inventor); Namkung, Min (Inventor); Simpson, John W. (Inventor)

2005-01-01

A giant magnetoresistive flux focusing eddy current device effectively detects deep flaws in thick multilayer conductive materials. The probe uses an excitation coil to induce eddy currents in conducting material perpendicularly oriented to the coil s longitudinal axis. A giant magnetoresistive (GMR) sensor, surrounded by the excitation coil, is used to detect generated fields. Between the excitation coil and GMR sensor is a highly permeable flux focusing lens which magnetically separates the GMR sensor and excitation coil and produces high flux density at the outer edge of the GMR sensor. The use of feedback inside the flux focusing lens enables complete cancellation of the leakage fields at the GMR sensor location and biasing of the GMR sensor to a location of high magnetic field sensitivity. In an alternate embodiment, a permanent magnet is positioned adjacent to the GMR sensor to accomplish the biasing. Experimental results have demonstrated identification of flaws up to 1 cm deep in aluminum alloy structures. To detect deep flaws about circular fasteners or inhomogeneities in thick multi-layer conductive materials, the device is mounted in a hand-held rotating probe assembly that is connected to a computer for system control, data acquisition, processing and storage.

The 3 micron spectrum of the classical Be star Beta Monocerotis A

NASA Technical Reports Server (NTRS)

Sellgren, K.; Smith, R. G.

1992-01-01

A 3.1-3.7-micron spectrum of the classical Be star Beta Mon A is presented at a resolution of lambda/Delta-lambda of 700-800. The spectrum shows strong hydrogen recombination lines, including Pf-delta and a series of Humphreys lines from Hu 19 to Hu 28. The relative recombination line strengths suggest that Pf-delta has a large optical depth. The Humphreys lines have relative strengths consistent with case B and may be optically thin. The line widths observed are broader than the Balmer lines and similar in width to Fe II lines, consistent with a disk model in which optically thinner lines arise primarily from a faster rotating inner disk, while optically thicker lines come mainly from a slower rotating outer disk. The apparent lack of Stark broadening of the Humphreys lines is used to place an upper limit on the circumstellar electron density of about 10 exp 12/cu cm.

Deglacial remobilization of permafrost carbon to sediments along the East Siberian Arctic Seas

NASA Astrophysics Data System (ADS)

Martens, J.; Wild, B.; Bröder, L.; Andersson, A.; Pearce, C.; O'Regan, M.; Jakobsson, M.; Tesi, T.; Muschitiello, F.; Sköld, M.; Semiletov, I. P.; Dudarev, O.; Gustafsson, O.

2017-12-01

Current climate change is expected to thaw large quantities of permafrost carbon (PF-C) and expose it to degradation which emits greenhouse gases (i.e. CO2 and CH4). Warming causes a gradual deepening of the seasonally thawed active layer surface of permafrost soils, but also the abrupt collapse of deeper Ice Complex Deposits (ICD), especially along Siberian coastlines. It was recently hypothesized that past warming already induced large-scale permafrost degradation after the last glacial, which ultimately amplified climate forcing. We here assess the mobilization of PF-C to East Siberian Arctic Sea sediments during these warming periods. We perform source apportionment using bulk carbon isotopes (ΔΔ14C, δ13C) together with terrestrial biomarkers (CuO-derived lignin phenols) as indicators for PF-C transfer. We apply these techniques to sediment cores (SWERUS-L2) from the Chukchi Sea (4-PC1) and the southern Lomonosov Ridge (31-PC1). We found that PF-C fluxes during the Bølling-Allerød warming (14.7 to 12.7 cal ka BP), the Younger Dryas cooling (12.7 to 11.7 cal ka BP) and the early Holocene warming (until 11 cal ka BP) were overall higher than mid and late Holocene fluxes. In the Chukchi Sea, PF-C burial was 2x higher during the deglaciation (7.2 g m-2 a-1) than in the mid and late Holocene (3.6 g m-2 a-1), and ICD were the dominant source of PF-C (79.1%). Smaller fractions originated from the active layer (9.1%) and marine sources (11.7%). We conclude that thermo-erosion of ICD released large amounts of PF-C to the Chukchi Sea, likely driven by climate warming and the deglacial sea level rise. This contrasts to earlier analyses of Laptev Sea sediments where active layer material from river transport dominated the carbon flux. Preliminary data on lignin phenol concentrations of Lomonosov Ridge sediments suggest that the postglacial remobilization of PF-C was one order of magnitude higher (10x) than during both the preceding glacial and the subsequent Holocene. We will apply source apportionments between coastal erosion of ICD and river export of active layer material for the outer East Siberian Arctic Seas. Our findings demonstrate remobilization of PF-C during past warming events and suggest that current climate change might cause a similar cascade of permafrost destabilization and, thus, accelerate climate warming.

Method and apparatus to trigger superconductors in current limiting devices

DOEpatents

Yuan, Xing; Hazelton, Drew Willard; Walker, Michael Stephen

2004-10-26

A method and apparatus for magnetically triggering a superconductor in a superconducting fault current limiter to transition from a superconducting state to a resistive state. The triggering is achieved by employing current-carrying trigger coil or foil on either or both the inner diameter and outer diameter of a superconductor. The current-carrying coil or foil generates a magnetic field with sufficient strength and the superconductor is disposed within essentially uniform magnetic field region. For superconductor in a tubular-configured form, an additional magnetic field can be generated by placing current-carrying wire or foil inside the tube and along the center axial line.

The nexin link and B-tubule glutamylation maintain the alignment of outer doublets in the ciliary axoneme.

PubMed

Alford, Lea M; Stoddard, Daniel; Li, Jennifer H; Hunter, Emily L; Tritschler, Douglas; Bower, Raqual; Nicastro, Daniela; Porter, Mary E; Sale, Winfield S

2016-06-01

We developed quantitative assays to test the hypothesis that the N-DRC is required for integrity of the ciliary axoneme. We examined reactivated motility of demembranated drc cells, commonly termed "reactivated cell models." ATP-induced reactivation of wild-type cells resulted in the forward swimming of ∼90% of cell models. ATP-induced reactivation failed in a subset of drc cell models, despite forward motility in live drc cells. Dark-field light microscopic observations of drc cell models revealed various degrees of axonemal splaying. In contrast, >98% of axonemes from wild-type reactivated cell models remained intact. The sup-pf4 and drc3 mutants, unlike other drc mutants, retain most of the N-DRC linker that interconnects outer doublet microtubules. Reactivated sup-pf4 and drc3 cell models displayed nearly wild-type levels of forward motility. Thus, the N-DRC linker is required for axonemal integrity. We also examined reactivated motility and axoneme integrity in mutants defective in tubulin polyglutamylation. ATP-induced reactivation resulted in forward swimming of >75% of tpg cell models. Analysis of double mutants defective in tubulin polyglutamylation and different regions of the N-DRC indicate B-tubule polyglutamylation and the distal lobe of the linker region are both important for axonemal integrity and normal N-DRC function. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Levitated Duct Fan (LDF) Aircraft Auxiliary Generator

NASA Technical Reports Server (NTRS)

Eichenberg, Dennis J.; Emerson, Dawn C.; Gallo, Christopher A.; Thompson, William K.

2011-01-01

This generator concept includes a novel stator and rotor architecture made from composite material with blades attached to the outer rotating shell of a ducted fan drum rotor, a non-contact support system between the stator and rotor using magnetic fields to provide levitation, and an integrated electromagnetic generation system. The magnetic suspension between the rotor and the stator suspends and supports the rotor within the stator housing using permanent magnets attached to the outer circumference of the drum rotor and passive levitation coils in the stator shell. The magnets are arranged in a Halbach array configuration.

The MIA complex is a conserved and novel dynein regulator essential for normal ciliary motility

PubMed Central

Yamamoto, Ryosuke; Song, Kangkang; Yanagisawa, Haru-aki; Fox, Laura; Yagi, Toshiki; Wirschell, Maureen; Hirono, Masafumi; Kamiya, Ritsu; Nicastro, Daniela

2013-01-01

Axonemal dyneins must be precisely regulated and coordinated to produce ordered ciliary/flagellar motility, but how this is achieved is not understood. We analyzed two Chlamydomonas reinhardtii mutants, mia1 and mia2, which display slow swimming and low flagellar beat frequency. We found that the MIA1 and MIA2 genes encode conserved coiled-coil proteins, FAP100 and FAP73, respectively, which form the modifier of inner arms (MIA) complex in flagella. Cryo–electron tomography of mia mutant axonemes revealed that the MIA complex was located immediately distal to the intermediate/light chain complex of I1 dynein and structurally appeared to connect with the nexin–dynein regulatory complex. In axonemes from mutants that lack both the outer dynein arms and the MIA complex, I1 dynein failed to assemble, suggesting physical interactions between these three axonemal complexes and a role for the MIA complex in the stable assembly of I1 dynein. The MIA complex appears to regulate I1 dynein and possibly outer arm dyneins, which are both essential for normal motility. PMID:23569216

Implementation of a long leg X-point target divertor in the ARC fusion pilot plant

NASA Astrophysics Data System (ADS)

Kuang, A. Q.; Cao, N. M.; Creely, A. J.; Dennett, C. A.; Hecla, J.; Hoffman, H.; Major, M.; Ruiz Ruiz, J.; Tinguely, R. A.; Tolman, E. A.; Brunner, D.; Labombard, B.; Sorbom, B. N.; Whyte, D. G.; Grover, P.; Laughman, C.

2017-10-01

A long leg X-point target divertor geometry in a double null geometry has been implemented in the ARC pilot plant design, exploiting ARC's demountable toroidal field (TF) coils and FLiBe immersion blanket, which allow superconducting poloidal field coils to be located inside the TF coils, adequately shielded from neutrons. This new design maintains the original TF coil size, core plasma shape, and attains a tritium breedin ratio 1.08. The long leg divertor geometry provides significant advantages. Neutron transport computations indicate a factor of 10 reduction in divertor material neutron damage rate compared to the first wall, easing requirements for high heat flux components. Simulations have shown that long legged divertors are able to maintain a passively stable detachment front that stays in the divertor leg over a wide power window, in principle, responding immediately to fast changes in power exhaust. The ARC design exploits this new paradigm for divertor heat flux control: fewer concerns about coping with fast transients and a focus on neutron-tolerant diagnostics to measure and adjust detachment front locations in the outer divertor legs over long timescales.

Development of model for studies on momentum transfer in electrochemical cells with entry region coil as turbulence promoter

NASA Astrophysics Data System (ADS)

Penta Rao, Tamarba; Rajendra Prasad, P.

2018-04-01

Entry region swirl promoters gain importance in industry because of its effectiveness in augmentation of mass and heat transfer augmentation. Design of equipment needs momentum transfer data along with mass or heat transfer data. Hence an experimental investigation was carried out with coaxially placed entry region spiral coil as turbulence promoters on momentum transfer in forced convection flow of electrolyte in circular conduits. Aqueous solution of sodium hydroxide and 0.01 M equimolal Ferri-ferro cyanide system was chosen for the study. The study covered parameters like effect of pitch of the coil, effect of length of the coil, diameter of the coil, diameter of the coil wire, diameter of the annular rod. The promoter is measured by limiting current technique using diffusion controlled electrochemical reactions. The study comprises of evaluation of momentum transfer rates at the outer wall of the electrochemical cell. Pressure drop measurements were also made to obtain the energy consumption pattern. Within the range of variables covered. The results are correlated by the momentum transfer similarity function. Momentum transfer coefficients were evaluated from measured limiting currents. Effect of each parameter was studied in terms of friction factor. A model was developed for momentum transfer. The experimental data on momentum transfer was modeled in terms of momentum transfer function and Reynolds number, geometric parameters.

Electromagnetic valve for controlling the flow of molten, magnetic material

DOEpatents

Richter, T.

1998-06-16

An electromagnetic valve for controlling the flow of molten, magnetic material is provided, which comprises an induction coil for generating a magnetic field in response to an applied alternating electrical current, a housing, and a refractory composite nozzle. The nozzle is comprised of an inner sleeve composed of an erosion resistant refractory material (e.g., a zirconia ceramic) through which molten, magnetic metal flows, a refractory outer shell, and an intermediate compressible refractory material, e.g., unset, high alumina, thermosetting mortar. The compressible refractory material is sandwiched between the inner sleeve and outer shell, and absorbs differential expansion stresses that develop within the nozzle due to extreme thermal gradients. The sandwiched layer of compressible refractory material prevents destructive cracks from developing in the refractory outer shell. 5 figs.

Electromagnetic valve for controlling the flow of molten, magnetic material

DOEpatents

Richter, Tomas

1998-01-01

An electromagnetic valve for controlling the flow of molten, magnetic material is provided, which comprises an induction coil for generating a magnetic field in response to an applied alternating electrical current, a housing, and a refractory composite nozzle. The nozzle is comprised of an inner sleeve composed of an erosion resistant refractory material (e.g., a zirconia ceramic) through which molten, magnetic metal flows, a refractory outer shell, and an intermediate compressible refractory material, e.g., unset, high alumina, thermosetting mortar. The compressible refractory material is sandwiched between the inner sleeve and outer shell, and absorbs differential expansion stresses that develop within the nozzle due to extreme thermal gradients. The sandwiched layer of compressible refractory material prevents destructive cracks from developing in the refractory outer shell.

Method of constructing a superconducting magnet

DOEpatents

Satti, John A.

1981-01-01

A superconducting magnet designed to produce magnetic flux densities of the order of 4 to 5 Webers per square meter is constructed by first forming a cable of a plurality of matrixed superconductor wires with each wire of the plurality insulated from each other one. The cable is shaped into a rectangular cross-section and is wound with tape in an open spiral to create cooling channels. Coils are wound in a calculated pattern in saddle shapes to produce desired fields, such as dipoles, quadrupoles, and the like. Wedges are inserted between adjacent cables as needed to maintain substantially radial placement of the long dimensions of cross sections of the cables. After winding, individual strands in each of the cables are brought out to terminals and are interconnected to place all of the strands in series and to maximize the propagation of a quench by alternating conduction from an inner layer to an outer layer and from top half to bottom half as often as possible. Individual layers are separated from others by spiraled aluminum spacers to facilitate cooling. The wound coil is wrapped with an epoxy tape that is cured by heat and then machined to an interference fit with an outer aluminum pipe which is then affixed securely to the assembled coil by heating it to make a shrink fit. In an alternate embodiment, one wire of the cable is made of copper or the like to be heated externally to propagate a quench.

Superconducting magnet

DOEpatents

Satti, John A.

1980-01-01

A superconducting magnet designed to produce magnetic flux densities of the order of 4 to 5 Webers per square meter is constructed by first forming a cable of a plurality of matrixed superconductor wires with each wire of the plurality insulated from each other one. The cable is shaped into a rectangular cross-section and is wound with tape in an open spiral to create cooling channels. Coils are wound in a calculated pattern in saddle shapes to produce desired fields, such as dipoles, quadrupoles, and the like. Wedges are inserted between adjacent cables as needed to maintain substantially radial placement of the long dimensions of cross sections of the cables. After winding, individual strands in each of the cables are brought out to terminals and are interconnected to place all of the strands in series and to maximize the propagation of a quench by alternating conduction from an inner layer to an outer layer and from top half to bottom half as often as possible. Individual layers are separated from others by spiraled aluminum spacers to facilitate cooling. The wound coil is wrapped with an epoxy tape that is cured by heat and then machined to an interference fit with an outer aluminum pipe which is then affixed securely to the assembled coil by heating it to make a shrink fit. In an alternate embodiment, one wire of the cable is made of copper or the like to be heated externally to propagate a quench.

ITER CS Model Coil and CS Insert Test Results

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

Martovetsky, N; Michael, P; Minervina, J

2000-09-07

The Inner and Outer modules of the Central Solenoid Model Coil (CSMC) were built by US and Japanese home teams in collaboration with European and Russian teams to demonstrate the feasibility of a superconducting Central Solenoid for ITER and other large tokamak reactors. The CSMC mass is about 120 t, OD is about 3.6 m and the stored energy is 640 MJ at 46 kA and peak field of 13 T. Testing of the CSMC and the CS Insert took place at Japan Atomic Energy Research Institute (JAERI) from mid March until mid August 2000. This paper presents the mainmore » results of the tests performed.« less

A wireless integrated circuit for 100-channel charge-balanced neural stimulation.

PubMed

Thurgood, B K; Warren, D J; Ledbetter, N M; Clark, G A; Harrison, R R

2009-12-01

The authors present the design of an integrated circuit for wireless neural stimulation, along with benchtop and in - vivo experimental results. The chip has the ability to drive 100 individual stimulation electrodes with constant-current pulses of varying amplitude, duration, interphasic delay, and repetition rate. The stimulation is performed by using a biphasic (cathodic and anodic) current source, injecting and retracting charge from the nervous system. Wireless communication and power are delivered over a 2.765-MHz inductive link. Only three off-chip components are needed to operate the stimulator: a 10-nF capacitor to aid in power-supply regulation, a small capacitor (< 100 pF) for tuning the coil to resonance, and a coil for power and command reception. The chip was fabricated in a commercially available 0.6- mum 2P3M BiCMOS process. The chip was able to activate motor fibers to produce muscle twitches via a Utah Slanted Electrode Array implanted in cat sciatic nerve, and to activate sensory fibers to recruit evoked potentials in somatosensory cortex.

Design comparison of single phase outer and inner-rotor hybrid excitation flux switching motor for hybrid electric vehicles

NASA Astrophysics Data System (ADS)

Mazlan, Mohamed Mubin Aizat; Sulaiman, Erwan; Husin, Zhafir Aizat; Othman, Syed Muhammad Naufal Syed; Khan, Faisal

2015-05-01

In hybrid excitation machines (HEMs), there are two main flux sources which are permanent magnet (PM) and field excitation coil (FEC). These HEMs have better features when compared with the interior permanent magnet synchronous machines (IPMSM) used in conventional hybrid electric vehicles (HEVs). Since all flux sources including PM, FEC and armature coils are located on the stator core, the rotor becomes a single piece structure similar with switch reluctance machine (SRM). The combined flux generated by PM and FEC established more excitation fluxes that are required to produce much higher torque of the motor. In addition, variable DC FEC can control the flux capabilities of the motor, thus the machine can be applied for high-speed motor drive system. In this paper, the comparisons of single-phase 8S-4P outer and inner rotor hybrid excitation flux switching machine (HEFSM) are presented. Initially, design procedures of the HEFSM including parts drawing, materials and conditions setting, and properties setting are explained. Flux comparisons analysis is performed to investigate the flux capabilities at various current densities. Then the flux linkages of PM with DC FEC of various DC FEC current densities are examined. Finally torque performances are analyzed at various armature and FEC current densities for both designs. As a result, the outer-rotor HEFSM has higher flux linkage of PM with DC FEC and higher average torque of approximately 10% when compared with inner-rotor HEFSM.

Development of an YBCO coil with SSTC conductors for high field application

NASA Astrophysics Data System (ADS)

Shi, Y.; Liu, H. J.; Liu, F.; Tan, Y. F.; Jin, H.; Yu, M.; Lei, L.; Guo, L.; Hong, Z. Y.

2018-07-01

With the continuous reduction of the production costs and improvement of the transport performance, YBCO coated conductor is the most promising candidate for the high field magnet application due to its high irreversibility field and strong mechanical properties. Presently a stable production capacity of the YBCO conductors has been achieved by Shanghai Superconducting Technology Co., Ltd (SSTC) in China. Therefore, the demand in high field application with YBCO conductors is growing in China. This paper describes the design, fabrication and preliminary experiment of a solenoid coil with YBCO conductors supplied by SSTC to validate the possibility of high field application. Four same double pancakes were manufactured and assembled for the YBCO coil where the outer diameter and height was 54.3 and 48 mm respectively to match the dimensional limitation of the 14 T background magnets. The critical current (Ic) of YBCO conductors was obtained by measuring as a function of the applied field perpendicular to the YBCO conductor surface which provides the necessary input parameters for preliminary performance evaluation of the coil. Finally the preliminary test and discussion at 77 and 4.2 K were carried out. The consistency of four double pancakes Ic was achieved. The measured results indicate that the fabrication technology of HTS coil is reliable which gives the conference for the in-field test in high field application. This YBCO coil is the first demonstration of the SSTC YBCO coated conductors.

High resolution NMR measurements using a 400MHz NMR with an (RE)Ba2Cu3O7-x high-temperature superconducting inner coil: Towards a compact super-high-field NMR.

PubMed

Piao, R; Iguchi, S; Hamada, M; Matsumoto, S; Suematsu, H; Saito, A T; Li, J; Nakagome, H; Takao, T; Takahashi, M; Maeda, H; Yanagisawa, Y

2016-02-01

Use of high-temperature superconducting (HTS) inner coils in combination with conventional low-temperature superconducting (LTS) outer coils for an NMR magnet, i.e. a LTS/HTS NMR magnet, is a suitable option to realize a high-resolution NMR spectrometer with operating frequency >1GHz. From the standpoint of creating a compact magnet, (RE: Rare earth) Ba2Cu3O7-x (REBCO) HTS inner coils which can tolerate a strong hoop stress caused by a Lorentz force are preferred. However, in our previous work on a first-generation 400MHz LTS/REBCO NMR magnet, the NMR resolution and sensitivity were about ten times worse than that of a conventional LTS NMR magnet. The result was caused by a large field inhomogeneity in the REBCO coil itself and the shielding effect of a screening current induced in that coil. In the present paper, we describe the operation of a modified 400MHz LTS/REBCO NMR magnet with an advanced field compensation technology using a combination of novel ferromagnetic shimming and an appropriate procedure for NMR spectrum line shape optimization. We succeeded in obtaining a good NMR line shape and 2D NOESY spectrum for a lysozyme aqueous sample. We believe that this technology is indispensable for the realization of a compact super-high-field high-resolution NMR. Copyright © 2016 Elsevier Inc. All rights reserved.

Preliminary Results of the 115 kJ Dense Plasma Focus Device IR-MPF-100

NASA Astrophysics Data System (ADS)

Salehizadeh, A.; Sadighzadeh, A.; Movahhed, M. Sedaghat; Zaeem, A. A.; Heidarnia, A.; Sabri, R.; Mahmoudi, M. Bakhshzad; Rahimi, H.; Rahimi, S.; Johari, E.; Torabi, M.; Damideh, V.

2013-04-01

This work summarizes the design and construction of the first Iranian 115 kJ Mather type plasma focus (PF) machine (IR-MPF-100). This machine consists of a 6.25 cm radius and 22 cm height brass made anode with a 50 mm height insulator which separates the anode and cathode electrodes. Twelve copper made 22 cm height rods play the role of cathode with 10.2 cm radius. Twenty four 6 μF capacitors were used with the maximum charging voltage of 40 kV (maximum energy of 115 kJ) as the capacitor bank and maximum theoretical current around 1.224 MA. The total inductance of the system is 120 nH. By using NE-102 plastic Scintillator, Rogowski coil, current and voltage probes, hard X-ray, current derivative, current and voltage signals of IR-MPF-100 were measured. The primary result of neutron detection by neutron activation counter represents approximately 109 neutrons per shot at 65 kJ discharge energy while using deuterium filling gas. Also IR-MPF-100 PF has been tested successfully at 90 kJ by using the argon gas.

Heat exchanger-accumulator

DOEpatents

Ecker, Amir L.

1980-01-01

What is disclosed is a heat exchanger-accumulator for vaporizing a refrigerant or the like, characterized by an upright pressure vessel having a top, bottom and side walls; an inlet conduit eccentrically and sealingly penetrating through the top; a tubular overflow chamber disposed within the vessel and sealingly connected with the bottom so as to define an annular outer volumetric chamber for receiving refrigerant; a heat transfer coil disposed in the outer volumetric chamber for vaporizing the liquid refrigerant that accumulates there; the heat transfer coil defining a passageway for circulating an externally supplied heat exchange fluid; transferring heat efficiently from the fluid; and freely allowing vaporized refrigerant to escape upwardly from the liquid refrigerant; and a refrigerant discharge conduit penetrating sealingly through the top and traversing substantially the length of the pressurized vessel downwardly and upwardly such that its inlet is near the top of the pressurized vessel so as to provide a means for transporting refrigerant vapor from the vessel. The refrigerant discharge conduit has metering orifices, or passageways, penetrating laterally through its walls near the bottom, communicating respectively interiorly and exteriorly of the overflow chamber for controllably carrying small amounts of liquid refrigerant and oil to the effluent stream of refrigerant gas.

A High-Resolution Endoscope of Small Diameter Using Electromagnetically Vibration of Single Fiber

NASA Astrophysics Data System (ADS)

Matsunaga, Tadao; Hino, Ryunosuke; Makishi, Wataru; Esashi, Masayoshi; Haga, Yoichi

For high resolution visual inspection in the narrow space of the human body, small diameter endoscope has been developed which utilize electromagnetically vibration of single fiber. Thin endoscopes are effective for inspection in the narrow space of the human body, for example, in the blood vessel, lactiferous duct for detection infiltration of breast cancer, and periodontal gap between gingiva and tooth. This endoscope consists of single optical fiber and photofabricated driving coils. A collimator lens and a cylindrical permanent magnet are fixed on the optical fiber, and the tilted driving coils have been patterned on a 1.08 mm outer diameter thin tube. The fiber is positioned at the center of the tube which is patterned the coils. When an electrical alternating current at the resonance frequency is supplied to the coils, the permanent magnet which is fixed to the fiber is vibrated electromagnetically and scanned one or two dimensionally. This paper reports small diameter endoscope by using electromagnetically vibration of single fiber. Optical coherence tomography imaging has also been carried out with the fabricated endoscope and cross-section image of sub-surface skin of thumb was observed.

Ultrastructural characterization of the tau-immunoreactive tubules in the oligodendroglial perikarya and their inner loop processes in progressive supranuclear palsy.

PubMed

Arima, K; Nakamura, M; Sunohara, N; Ogawa, M; Anno, M; Izumiyama, Y; Hirai, S; Ikeda, K

1997-06-01

Coiled bodies and interfascicular threads are conspicuous white matter abnormalities of brains of patients with progressive supranuclear palsy (PSP). Both structures are argyrophilic and immunoreactive for the microtubule-binding protein tau. This report concerns the ultrastructural localization of interfascicular threads and their relationship to coiled bodies in five PSP patients. We showed for the first time that abnormal tubules with a 13- to 15-nm diameter and fuzzy outer contours were the common structures of coiled bodies in the oligodendroglial perikarya and of interfascicular threads. Moreover, the tubules were immunolabeled by anti-tau antibodies. The abnormal tau-positive tubules of interfascicular threads were located in the inner loop of the myelin sheath. Our study further indicated that the thread-like structures in the white matter comprised, at least in part, oligodendroglial processes, and that they were also present in gray matter. We consider that the formation of coiled bodies in the perikarya and of interfascicular threads represents a common cytoskeletal abnormality of the oligodendroglia of PSP patients. Moreover, even though the white matter alterations of PSP resemble those of corticobasal degeneration, there are certain ultrastructural differences in the abnormal oligodendroglial tubules of the two diseases.

Mechanical qualification of the support structure for MQXF, the Nb 3Sn low-β quadrupole for the high luminosity LHC

DOE PAGES

Juchno, M.; Ambrosio, G.; Anerella, M.; ...

2016-01-26

Within the scope of the High Luminosity LHC project, the collaboration between CERN and U.S. LARP is developing new low-β quadrupoles using the Nb 3Sn superconducting technology for the upgrade of the LHC interaction regions. The magnet support structure of the first short model was designed and two units were fabricated and tested at CERN and at LBNL. The structure provides the preload to the collars-coils subassembly by an arrangement of outer aluminum shells pre-tensioned with water-pressurized bladders. For the mechanical qualification of the structure and the assembly procedure, superconducting coils were replaced with solid aluminum “dummy coils”, the structuremore » was preloaded at room temperature, and then cooled-down to 77 K. Mechanical behavior of the magnet structure was monitored with the use of strain gauges installed on the aluminum shells, the dummy coils and the axial preload system. As a result, this paper reports on the outcome of the assembly and the cool-down tests with dummy coils, which were performed at CERN and at LBNL, and presents the strain gauge measurements compared to the 3D finite element model predictions.« less

Test of an 8.66-T REBCO Insert Coil with Overbanding Radial Build for a 1.3-GHz LTS/HTS NMR Magnet.

PubMed

Qu, Timing; Michael, Philip C; Bascuñán, Juan; Lécrevisse, Thibault; Guan, Mingzhi; Hahn, Seungyong; Iwasa, Yukikazu

2017-06-01

A 1.3-GHz/54-mm LTS/HTS NMR magnet, assembled with a 3-coil (Coils 1-3) 800-MHz HTS insert in a 500-MHz LTS NMR magnet, is under construction. The innermost HTS insert Coil 1 has a stack of 26 no-insulation (NI) double pancake (DP) coils wound of 6-mm wide and 75- μ m thick REBCO tapes. In order to keep the hoop strains on REBCO tape < 0.6% at an operating current I op of 250 A and in a field of 30.5 T, we overbanded each pancake in Coil 1 with a 6-mm wide, 76- μ m thick 304 stainless steel strip: 7-mm thick radial build for the central 18 pancakes, while 6-mm thick for the outer 2×17 pancakes. In this paper, Coil 1 was successfully tested at 77K and 4.2 K. In the 77-K test, the measured critical current was 35.7 A, determined by an E -field criterion of 0.1 μ V/cm. The center field magnet constant decreased from 34.2 mT/A to 29.3 mT/A, when I op increased from 5 A to 40 A. The field distribution at different I op along the z -axis was measured. The residual field distributions discharged from 10 A and 20 A were recorded. In the 4.2-K test, Coil 1 successfully generated a central field of 8.78 T at 255 A. The magnet constant is 34.4 mT/A, which is same as our designed value. The field homogeneity at the coil center within a ± 15-mm region is around 1700 ppm. This large error field must be reduced before field shimming is applied.

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

Michael Viola, J. Edwards, T. Brown, L. Dudek, R. Ellis, P. Heitzenroeder, R. Strykowsky and Michael Cole

The National Compact Stellarator Experiment (NCSX) was a collaborative effort between ORNL and PPPL. PPPL provided the assembly techniques with guidance from ORNL to meet design criteria. The individual vacuum vessel segments, modular coils, trim coils, and toroidal field coils components were delivered to the Field Period Assembly (FPA) crew who then would complete the component assemblies and then assemble the final three field period assemblies, each consisting of two sets of three modular coils assembled over a 120o vacuum vessel segment with the trim coils and toroidal field coils providing the outer layer. The requirements for positioning the modularmore » coils were found to be most demanding. The assembly tolerances required for accurate positioning of the field coil windings in order to generate sufficiently accurate magnetic fields strained state of the art techniques in metrology and alignment and required constant monitoring of assembly steps with laser trackers, measurement arms, and photogrammetry. The FPA activities were being performed concurrently while engineering challenges were being resolved. For example, it was determined that high friction electrically isolated shims were needed between the modular coil interface joints and low distortion welding was required in the nose region of those joints. This took months of analysis and development yet the assembly was not significantly impacted because other assembly tasks could be performed in parallel with ongoing assembly tasks as well as tasks such as advance tooling setup preparation for the eventual welding tasks. The crew technicians developed unique, accurate time saving techniques and tooling which provided significant cost and schedule savings. Project management displayed extraordinary foresight and every opportunity to gain advanced knowledge and develop techniques was taken advantage of. Despite many risk concerns, the cost and schedule performance index was maintained nearly 1.0 during the assembly phase until project cancellation. In this paper, the assembly logic, the engineering challenges, solutions to those challenges and some of the unique and clever assembly techniques, will be presented.« less

Study of a wireless power transmission system for an active capsule endoscope.

PubMed

Xin, Wenhui; Yan, Guozheng; Wang, Wenxin

2010-03-01

An active capsule endoscope (ACE) will consume much more energy than can be power by batteries. Its orientation and position are always undetermined when it continues the natural way down the gastrointestinal track. In order to deliver stable and sufficient energy to ACE safely, a wireless power transmission system based on inductive coupling is presented. The system consists of a Helmholtz primary coil outside and a multiple secondary coils inside the body. The Helmholtz primary coil is driven to generate a uniform alternating magnetic field covering the whole of the alimentary tract, and the multiple secondary coils receive energy regardless of the ACE's position and orientation relative to the generated magnetic field. The human tissue safety of the electromagnetic field generated by transmitting coil was evaluated, based on a high-resolution realistic human model. At least 310 mW usable power can be transmitted under the worst geometrical conditions. Outer dimensions of the power receiver, 10 mm diameter x 12 mm; transmitting power, 25 W; resonant frequency, 400 kHz. The maximum specific absorption rate (SAR) and current density of human tissues are 0.329 W/kg and 3.82 A/m(2), respectively, under the basic restrictions of the International Commission on Non-ionizing Radiation Protection (ICNIRP). The designed wireless power transmission is shown to be feasible and potentially safe in a future application. (c) 2010 John Wiley & Sons, Ltd.

Conceptual design of a 24-32 MW radially-cooled insert for a greater than or = 45 T hybrid system

NASA Astrophysics Data System (ADS)

Weggel, Robert J.; Hake, Michael E.; Stejskal, Vladimir

1994-07-01

The FBNML is designing and will fabricate a radially-cooled insert magnet to generate 70% of the field of a system, Hybrid V, to surpass 45 T in a 32 mm bore. The insert is to have an overall diameter and a maximum active coil length of 610 mm. With a background field of 14 T the system should generate 47 T at 24 MW and nearly 49 T at 32 MW. The peak stress is extremely high, calling for conductors such as Be-Cu (UNS C17510) and 24% Ag-Cu with strengths up to 1100 MPa. The peak heat flux density also is high, nearly 12 W/mm(exp 2). Because the water is coldest and its velocity highest where the heat flux is highest, however, the peak temperature is only 80 C. The water flow is approximately = 200 l/s at 27 atm. The system is to be very user friendly. Access is completely unobstructed at the top. Insert removal leaves the plumbing and electrical connections intact. The massive and expensive outer coils should be long lived, the inner coil easily replaceable. During an inner coil burnout, a sleeve intercepts arcing from the inner coil to the middle one, reducing burnout severity and fault loads. The insert should be a worthy successor to those of the FBNML's world-record holding systems, Hybrids II and III.

A persistent-mode 0.5 T solid-nitrogen-cooled MgB2 magnet for MRI.

PubMed

Ling, Jiayin; Voccio, John P; Hahn, Seungyong; Qu, Timing; Bascuñán, Juan; Iwasa, Yukikazu

2017-02-01

This paper presents construction details and test results of a persistent-mode 0.5-T MgB 2 magnet developed at the Francis Bitter Magnet Lab, MIT. The magnet, of 276-mm inner diameter and 290-mm outer diameter, consisted of a stack of 8 solenoidal coils with a total height of 460 mm. Each coil was wound with monofilament MgB 2 wire, equipped with a persistent-current switch and terminated with a superconducting joint, forming an individual superconducting loop. Resistive solder joints connected the 8 coils in series. The magnet, after being integrated into a testing system, immersed in solid nitrogen, was operated in a temperature range of 10-13 K. A two-stage cryocooler was deployed to cool a radiation shield and the cold mass that included mainly ~60 kg of solid nitrogen and the magnet. The solid nitrogen was capable of providing a uniform and stable cryogenic environment to the magnet. The magnet sustained a 0.47-T magnetic field at its center persistently in a range of 10-13 K. The current in each coil was inversely calculated from the measured field profile to determine the performance of each coil in persistent-mode operation. Persistent-current switches were successfully operated in solid nitrogen for ramping the magnet. They were also designed to absorb magnetic energy in a protection mechanism; its effectiveness was evaluated in an induced quench.

Post-assembly magnetization of a 100 kW high speed permanent magnet rotor.

PubMed

Lv, Yiliang; Wang, Guobin; Li, Liang

2015-03-01

A post-assembly magnetizing fixture has been designed and successfully used to magnetize the rotor of a 100 kW high speed permanent magnet synchronous motor. The rotor is a solid cylinder with outer diameter of 80 mm and total length of 515 mm. The permanent magnet material is samarium-cobalt (Sm2Co17) with saturation magnetizing field of 6 T. The mechanical stability of the magnetizing fixture has been studied as well as the general design methodology. The magnetizing coil is subdivided in order to reduce the electromagnetic force, and the coils are separately reinforced in different ways. The electromagnetic and structural optimization is performed by finite element analysis and verified by experiments.

Nonazeotropic Heat Pump

NASA Technical Reports Server (NTRS)

Ealker, David H.; Deming, Glenn

1991-01-01

Heat pump collects heat from water circulating in heat-rejection loop, raises temperature of collected heat, and transfers collected heat to water in separate pipe. Includes sealed motor/compressor with cooling coils, evaporator, and condenser, all mounted in outer housing. Gradients of temperature in evaporator and condenser increase heat-transfer efficiency of vapor-compression cycle. Intended to recover relatively-low-temperature waste heat and use it to make hot water.

Simple method for RF pulse measurement using gradient reversal.

PubMed

Landes, Vanessa L; Nayak, Krishna S

2018-05-01

To develop and evaluate a simple method for measuring the envelope of small-tip radiofrequency (RF) excitation waveforms in MRI, without extra hardware or synchronization. Gradient reversal approach to evaluate RF (GRATER) involves RF excitation with a constant gradient and reversal of that gradient during signal reception to acquire the time-reversed version of an RF envelope. An outer-volume suppression prepulse is used optionally to preselect a uniform volume. GRATER was evaluated in phantom and in vivo experiments. It was compared with the programmed waveform and the traditional pick-up coil method. In uniform phantom experiments, pick-up coil, GRATER, and outer-volume suppression + GRATER matched the programmed waveforms to less than 2.1%, less than 6.1%, and less than 2.4% normalized root mean square error, respectively, for real RF pulses with flip angle less than or equal to 30°, time-bandwidth product 2 to 8, and two to five excitation bands. For flip angles greater than 30°, GRATER measurement error increased as predicted by Bloch simulation. Fat-water phantom and in vivo experiments with outer-volume suppression + GRATER demonstrated less than 6.4% normalized root mean square error. The GRATER sequence measures small-tip RF envelopes without extra hardware or synchronization in just over two times the RF duration. The sequence may be useful in prescan calibration and for measurement and precompensation of RF amplifier nonlinearity. Magn Reson Med 79:2642-2651, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Segmented surface coil resonator for in vivo EPR applications at 1.1GHz.

PubMed

Petryakov, Sergey; Samouilov, Alexandre; Chzhan-Roytenberg, Michael; Kesselring, Eric; Sun, Ziqi; Zweier, Jay L

2009-05-01

A four-loop segmented surface coil resonator (SSCR) with electronic frequency and coupling adjustments was constructed with 18mm aperture and loading capability suitable for in vivo Electron Paramagnetic Resonance (EPR) spectroscopy and imaging applications at L-band. Increased sample volume and loading capability were achieved by employing a multi-loop three-dimensional surface coil structure. Symmetrical design of the resonator with coupling to each loop resulted in high homogeneity of RF magnetic field. Parallel loops were coupled to the feeder cable via balancing circuitry containing varactor diodes for electronic coupling and tuning over a wide range of loading conditions. Manually adjusted high Q trimmer capacitors were used for initial tuning with subsequent tuning electronically controlled using varactor diodes. This design provides transparency and homogeneity of magnetic field modulation in the sample volume, while matching components are shielded to minimize interference with modulation and ambient RF fields. It can accommodate lossy samples up to 90% of its aperture with high homogeneity of RF and modulation magnetic fields and can function as a surface loop or a slice volume resonator. Along with an outer coaxial NMR surface coil, the SSCR enabled EPR/NMR co-imaging of paramagnetic probes in living rats to a depth of 20mm.

Segmented surface coil resonator for in vivo EPR applications at 1.1 GHz

PubMed Central

Petryakov, Sergey; Samouilov, Alexandre; Chzhan-Roytenberg, Michael; Kesselring, Eric; Sun, Ziqi; Zweier, Jay L.

2010-01-01

A four-loop segmented surface coil resonator (SSCR) with electronic frequency and coupling adjustments was constructed with 18 mm aperture and loading capability suitable for in vivo Electron Paramagnetic Resonance (EPR) spectroscopy and imaging applications at L-band. Increased sample volume and loading capability were achieved by employing a multi-loop three-dimensional surface coil structure. Symmetrical design of the resonator with coupling to each loop resulted in high homogeneity of RF magnetic field. Parallel loops were coupled to the feeder cable via balancing circuitry containing varactor diodes for electronic coupling and tuning over a wide range of loading conditions. Manually adjusted high Q trimmer capacitors were used for initial tuning with subsequent tuning electronically controlled using varactor diodes. This design provides transparency and homogeneity of magnetic field modulation in the sample volume, while matching components are shielded to minimize interference with modulation and ambient RF fields. It can accommodate lossy samples up to 90% of its aperture with high homogeneity of RF and modulation magnetic fields and can function as a surface loop or a slice volume resonator. Along with an outer coaxial NMR surface coil, the SSCR enabled EPR/NMR co-imaging of paramagnetic probes in living rats to a depth of 20 mm. PMID:19268615

Displacement sensing system and method

DOEpatents

VunKannon, Jr., Robert S

2006-08-08

A displacement sensing system and method addresses demanding requirements for high precision sensing of displacement of a shaft, for use typically in a linear electro-dynamic machine, having low failure rates over multi-year unattended operation in hostile environments. Applications include outer space travel by spacecraft having high-temperature, sealed environments without opportunity for servicing over many years of operation. The displacement sensing system uses a three coil sensor configuration, including a reference and sense coils, to provide a pair of ratio-metric signals, which are inputted into a synchronous comparison circuit, which is synchronously processed for a resultant displacement determination. The pair of ratio-metric signals are similarly affected by environmental conditions so that the comparison circuit is able to subtract or nullify environmental conditions that would otherwise cause changes in accuracy to occur.

Design and modeling of energy generated magneto rheological damper

NASA Astrophysics Data System (ADS)

Ahamed, Raju; Rashid, Muhammad Mahbubur; Ferdaus, Md Meftahul; Yusof, Hazlina Md.

2016-02-01

In this paper an energy generated mono tube MR damper model has been developed for vehicle suspension systems. A 3D model of energy generated MR damper is developed in Solid Works electromagnetic simulator (EMS) where it is analyzed extensively by finite element method. This dynamic simulation clearly illustrates the power generation ability of the damper. Two magnetic fields are induced inside this damper. One is in the outer coil of the power generator and another is in the piston head coils. The complete magnetic isolation between these two fields is accomplished here, which can be seen in the finite element analysis. The induced magnetic flux densities, magnetic field intensities of this damper are analyzed for characterizing the damper's power generation ability. Finally, the proposed MR damper's energy generation ability was studied experimentally.

A persistent-mode 0.5 T solid-nitrogen-cooled MgB2 magnet for MRI

PubMed Central

Ling, Jiayin; Voccio, John P.; Hahn, Seungyong; Qu, Timing; Bascuñán, Juan; Iwasa, Yukikazu

2017-01-01

This paper presents construction details and test results of a persistent-mode 0.5-T MgB2 magnet developed at the Francis Bitter Magnet Lab, MIT. The magnet, of 276-mm inner diameter and 290-mm outer diameter, consisted of a stack of 8 solenoidal coils with a total height of 460 mm. Each coil was wound with monofilament MgB2 wire, equipped with a persistent-current switch and terminated with a superconducting joint, forming an individual superconducting loop. Resistive solder joints connected the 8 coils in series. The magnet, after being integrated into a testing system, immersed in solid nitrogen, was operated in a temperature range of 10–13 K. A two-stage cryocooler was deployed to cool a radiation shield and the cold mass that included mainly ~60 kg of solid nitrogen and the magnet. The solid nitrogen was capable of providing a uniform and stable cryogenic environment to the magnet. The magnet sustained a 0.47-T magnetic field at its center persistently in a range of 10–13 K. The current in each coil was inversely calculated from the measured field profile to determine the performance of each coil in persistent-mode operation. Persistent-current switches were successfully operated in solid nitrogen for ramping the magnet. They were also designed to absorb magnetic energy in a protection mechanism; its effectiveness was evaluated in an induced quench. PMID:28966476

Advanced Divertor Design and Application under Modern Superconducting Tokamak Constraints

NASA Astrophysics Data System (ADS)

Covele, Brent; Kotschenreuther, Mike; Mahajan, Swadesh; Valanju, Prashant

2013-10-01

With current ITER projections already predicting divertor exhaust heat loads in the 5-10 MW/m2 range, i.e. at the maximum tolerance, it is clear that the divertor heat load problem will only be exacerbated for future superconducting tokamaks, as well as perhaps some modern tokamaks today. Thus, an advanced divertor, such as the X-Divertor (XD), Super-X Divertor (SXD), or Snowflake (SF) will become a virtual necessity to reduce incident heat flux at the target plates. Using the 2D magnetic equilibrium code CORSICA, we explore the possibilities of creating an advanced divertor for a next-generation superconducting tokamak (Ip = 15 MA, BT = 5.3 T, R = 6.2 m) under nominal engineering constraints. Advanced divertors were achieved with no in-vessel PF coils, PF current densities below 30 MA/m2, and vertical maintenance access, all of which are favorable conditions for tokamaks today. Both the XD and SF divertors are readily achievable while maintaining core plasma performance, and the advantages and disadvantages of each are discussed in turn. Some thought is given as to how the divertor cassette will need to be modified to accommodate advanced divertors. Work supported under US-DOE projects DE-FG02-04ER54742 and DE-FG02-04ER54754.

Fixing Stellarator Magnetic Surfaces

NASA Astrophysics Data System (ADS)

Hanson, James D.

1999-11-01

Magnetic surfaces are a perennial issue for stellarators. The design heuristic of finding a magnetic field with zero perpendicular component on a specified outer surface often yields inner magnetic surfaces with very small resonant islands. However, magnetic fields in the laboratory are not design fields. Island-causing errors can arise from coil placement errors, stray external fields, and design inadequacies such as ignoring coil leads and incomplete characterization of current distributions within the coil pack. The problem addressed is how to eliminate such error-caused islands. I take a perturbation approach, where the zero order field is assumed to have good magnetic surfaces, and comes from a VMEC equilibrium. The perturbation field consists of error and correction pieces. The error correction method is to determine the correction field so that the sum of the error and correction fields gives zero island size at specified rational surfaces. It is particularly important to correctly calculate the island size for a given perturbation field. The method works well with many correction knobs, and a Singular Value Decomposition (SVD) technique is used to determine minimal corrections necessary to eliminate islands.

Design Optimization of an Electromagnetic Energy Harvester Backpack for Utilization of Human Walking Energy

NASA Astrophysics Data System (ADS)

Mullen, Christopher

Implementation of energy harvesting technology can provide a sustainable, remote power source for soldiers by reducing the battery weight and allowing them to stay in the field for longer periods of time. Among multiple energy conversion principles, electromagnetic induction can scavenge energy from wasted kinematic and vibration energy found from human motion. Hip displacement during human gait acts as a base excitation for an energy harvesting backpack system. The placement of a permanent magnet in this vibration environment results in relative motion of the magnet to the coil of copper wire, which induces an electric current. This current can be saved to a battery or capacitor bank installed on the backpack to be used to power electronic devices. The purpose of this research is to construct a reliable simulation model for an electromagnetic vibration energy harvester and use it for a multi-variable optimization algorithm to identify an optimal coil and magnet layout for highest power output. Key components of the coupled equations of motion such as the magnetic flux density and coil inductance are obtained using ANSYS multi-physics software or by measuring them. These components are fed into a harvester simulation model (e.g. coupled field equations of motion for the backpack harvester) that generates the electrical power output. The developed simulation model is verified with multiple case studies including an experimental test. Then the optimal design parameters in the simulation model (e.g., magnet layout, coil width, outer coil diameter, external load resistance) are identified for maximum power. Results from this study will pave the way for a more efficient energy harvesting backpack while providing better insight into the efficiency of magnet and coil layout for electromagnetic applications.

Experimental verification and optimization of a linear electromagnetic energy harvesting device

NASA Astrophysics Data System (ADS)

Mullen, Christopher; Lee, Soobum

2017-04-01

Implementation of energy harvesting technology can provide a sustainable, remote power source for soldiers by reducing the battery weight and allowing them to stay in the field for longer periods of time. Among multiple energy conversion principles, electromagnetic induction can scavenge energy from wasted kinematic and vibration energy found from human motion. Hip displacement during human gait acts as a base excitation for an energy harvesting backpack system. The placement of a permanent magnet in this vibration environment results in relative motion of the magnet to the coil of copper wire, which induces an electric current. This current can be saved to a battery or capacitor bank installed on the backpack to be used to power electronic devices. The purpose of this research is to construct a reliable simulation model for an electromagnetic vibration energy harvester and use it for a multi-variable optimization algorithm to identify an optimal coil and magnet layout for highest power output. Key components of the coupled equations of motion such as the magnetic flux density and coil inductance are obtained using ANSYS multi-physics software or by measuring them. These components are fed into a harvester simulation model (e.g. coupled field equations of motion for the backpack harvester) that generates the electrical power output. The developed simulation model is verified with a case study including an experimental test. Then the optimal design parameters in the simulation model (e.g., magnet layout, coil width, outer coil diameter, external load resistance) are identified for maximum power. Results from this study will pave the way for a more efficient energy harvesting backpack while providing better insight into the efficiency of magnet and coil layout for electromagnetic applications.

Parametric design studies of toroidal magnetic energy storage units

NASA Astrophysics Data System (ADS)

Herring, J. Stephen

Superconducting magnetic energy storage (SMES) units have a number of advantages as storage devices. Electrical current is the input, output and stored medium, allowing for completely solid-state energy conversion. The magnets themselves have no moving parts. The round trip efficiency is higher than those for batteries, compressed air or pumped hydro. Output power can be very high, allowing complete discharge of the unit within a few seconds. Finally, the unit can be designed for a very large number of cycles, limited basically by fatigue in the structural components. A small systems code was written to produce and evaluate self-consistent designs for toroidal superconducting energy storage units. The units can use either low temperature or high temperature superconductors. The coils have D shape where the conductor and its stabilizer/structure is loaded only in tension and the centering forces are borne by a bucking cylinder. The coils are convectively cooled from a cryogenic reservoir in the bore of the coils. The coils are suspended in a cylindrical metal shell which protects the magnet during rail, automotive or shipboard use. It is important to note that the storage unit does not rely on its surroundings for structural support, other than normal gravity and inertial loads. Designs are presented for toroidal energy storage units produced by the systems code. A wide range of several parameters have been considered, resulting in units storing from 1 MJ to 72 GJ. Maximum fields range from 5 T to 20 T. The masses and volumes of the coils, bucking cylinder, coolant, insulation and outer shell are calculated. For unattended use, the allowable operating time using only the boiloff of the cryogenic fluid for refrigeration is calculated. For larger units, the coils were divided into modules suitable for normal truck or rail transport.

Gradient rotating outer volume excitation (GROOVE): A novel method for single-shot two-dimensional outer volume suppression.

PubMed

Powell, Nathaniel J; Jang, Albert; Park, Jang-Yeon; Valette, Julien; Garwood, Michael; Marjańska, Małgorzata

2015-01-01

To introduce a new outer volume suppression (OVS) technique that uses a single pulse and rotating gradients to accomplish frequency-swept excitation. This new technique, which is called gradient rotating outer volume excitation (GROOVE), produces a circular or elliptical suppression band rather than suppressing the entire outer volume. Theoretical and k-space descriptions of GROOVE are provided. The properties of GROOVE were investigated with simulations, phantom, and human experiments performed using a 4T horizontal bore magnet equipped with a TEM coil. Similar suppression performance was obtained in phantom and human brain using GROOVE with circular and elliptical shapes. Simulations indicate that GROOVE requires less SAR and time than traditional OVS schemes, but traditional schemes provide a sharper transition zone and less residual signal. GROOVE represents a new way of performing OVS in which spins are excited temporally in space on a trajectory that can be tailored to fit the shape of the suppression region. In addition, GROOVE is capable of suppressing tailored regions of space with more flexibility and in a shorter period of time than conventional methods. GROOVE provides a fast, low SAR alternative to conventional OVS methods in some applications (e.g., scalp suppression). © 2014 Wiley Periodicals, Inc.

Magnet Design and Analysis of a 40 Tesla Long Pulse System Energized by a Battery Bank

NASA Astrophysics Data System (ADS)

Lv, Y. L.; Peng, T.; Wang, G. B.; Ding, T. H.; Han, X. T.; Pan, Y.; Li, L.

2013-03-01

A 40 tesla long pulse magnet and a battery bank as the power supply have been designed. This is now under construction at the Wuhan National High Magnetic Field Center. The 22 mm bore magnet will generate smooth pulses with duration 1 s and rise time 0.5 s. The battery bank consists of 945 12V/200 Ah lead-acid battery cells. The magnet and battery bank were optimized by codes developed in-house and by ANSYS. The coil was made from soft copper with internal reinforcement by fiber-epoxy composite; it is divided into two sections connected in series. The inner section consists of helix coils with each layer reinforced by Zylon composite. The outer section will be wound from copper sheet and externally reinforced by carbon fiber composite.

Structure of the periplasmic adaptor protein from a major facilitator superfamily (MFS) multidrug efflux pump.

PubMed

Hinchliffe, Philip; Greene, Nicholas P; Paterson, Neil G; Crow, Allister; Hughes, Colin; Koronakis, Vassilis

2014-08-25

Periplasmic adaptor proteins are key components of bacterial tripartite efflux pumps. The 2.85 Å resolution structure of an MFS (major facilitator superfamily) pump adaptor, Aquifex aeolicus EmrA, shows linearly arranged α-helical coiled-coil, lipoyl, and β-barrel domains, but lacks the fourth membrane-proximal domain shown in other pumps to interact with the inner membrane transporter. The adaptor α-hairpin, which binds outer membrane TolC, is exceptionally long at 127 Å, and the β-barrel contains a conserved disordered loop. The structure extends the view of adaptors as flexible, modular components that mediate diverse pump assembly, and suggests that in MFS tripartite pumps a hexamer of adaptors could provide a periplasmic seal. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

On the recovery of electric currents in the liquid core of the Earth

NASA Astrophysics Data System (ADS)

Kuslits, Lukács; Prácser, Ernő; Lemperger, István

2017-04-01

Inverse geodynamo modelling has become a standard method to get a more accurate image of the processes within the outer core. In this poster excerpts from the preliminary results of an other approach are presented. This comes around the possibility of recovering the currents within the liquid core directly, using Main Magnetic Field data. The approximation of different systems of the flow of charge is possible with various geometries. Based on previous geodynamo simulations, current coils can furnish a good initial geometry for such an estimation. The presentation introduces our preliminary test results and the study of reliability of the applied inversion algorithm for different numbers of coils, distributed in a grid simbolysing the domain between the inner-core and core-mantle boundaries. We shall also present inverted current structures using Main Field model data.

Using fiberglass volumes for VPI of superconductive magnetic systems’ insulation

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

Andreev, I. S.; Bezrukov, A. A.; Pischugin, A. B.

2014-01-29

The paper describes the method of manufacturing fiberglass molds for vacuum pressure impregnation (VPI) of high-voltage insulation of superconductive magnetic systems (SMS) with epoxidian hot-setting compounds. The basic advantages of using such vacuum volumes are improved quality of insulation impregnation in complex-shaped areas, and considerable cost-saving of preparing VPI of large-sized components due to dispensing with the stage of fabricating a metal impregnating volume. Such fiberglass vacuum molds were used for VPI of high-voltage insulation samples of an ITER reactor’s PF1 poloidal coil. Electric insulation of these samples has successfully undergone a wide range of high-voltage and mechanical tests atmore » room and cryogenic temperatures. Some results of the tests are also given in this paper.« less

A temperature-jump NMR probe setup using rf heating optimized for the analysis of temperature-induced biomacromolecular kinetic processes

NASA Astrophysics Data System (ADS)

Rinnenthal, Jörg; Wagner, Dominic; Marquardsen, Thorsten; Krahn, Alexander; Engelke, Frank; Schwalbe, Harald

2015-02-01

A novel temperature jump (T-jump) probe operational at B0 fields of 600 MHz (14.1 Tesla) with an integrated cage radio-frequency (rf) coil for rapid (<1 s) heating in high-resolution (HR) liquid-state NMR-spectroscopy is presented and its performance investigated. The probe consists of an inner 2.5 mm "heating coil" designed for generating rf-electric fields of 190-220 MHz across a lossy dielectric sample and an outer two coil assembly for 1H-, 2H- and 15N-nuclei. High B0 field homogeneities (0.7 Hz at 600 MHz) are combined with high heating rates (20-25 K/s) and only small temperature gradients (<±1.5 K, 3 s after 20 K T-jump). The heating coil is under control of a high power rf-amplifier within the NMR console and can therefore easily be accessed by the pulse programmer. Furthermore, implementation of a real-time setup including synchronization of the NMR spectrometer's air flow heater with the rf-heater used to maintain the temperature of the sample is described. Finally, the applicability of the real-time T-jump setup for the investigation of biomolecular kinetic processes in the second-to-minute timescale is demonstrated for samples of a model 14mer DNA hairpin and a 15N-selectively labeled 40nt hsp17-RNA thermometer.

Three-layered radio frequency coil arrangement for sodium MRI of the human brain at 9.4 Tesla.

PubMed

Shajan, G; Mirkes, Christian; Buckenmaier, Kai; Hoffmann, Jens; Pohmann, Rolf; Scheffler, Klaus

2016-02-01

A multinuclei imaging setup with the capability to acquire both sodium ((23) Na) and proton ((1) H) signals at 9.4 Tesla is presented. The main objective was to optimize coil performance at the (23) Na frequency while still having the ability to acquire satisfactory (1) H images. The setup consisted of a combination of three radio frequency (RF) coils arranged in three layers: the innermost layer was a 27-channel (23) Na receive helmet which was surrounded by a four-channel (23) Na transceiver array. The outer layer consisted of a four-channel (1) H dipole array for B0 shimming and anatomical localization. Transmit and receive performance of the (23) Na arrays was compared to a single-tuned (23) Na birdcage resonator. While the transmit efficiency of the (23) Na transceiver array was comparable to the birdcage, the (23) Na receive array provided substantial signal-to-noise ratio (SNR) gain near the surface and comparable SNR in the center. The utility of this customized setup was demonstrated by (23) Na images of excellent quality. High SNR, efficient transmit excitation and B0 shimming capability can be achieved for (23) Na MRI at 9.4T using novel coil combination. This RF configuration is easily adaptable to other multinuclei applications at ultra high field (≥ 7T). © 2015 Wiley Periodicals, Inc.

Anatomical and metabolic assessment of prostate using a 3-Tesla MR scanner with a custom-made external transceive coil: healthy volunteer study.

PubMed

Kaji, Yasushi; Kuroda, Kagayaki; Maeda, Takaki; Kitamura, Yuri; Fujiwara, Toshitaka; Matsuoka, Yuichiro; Tamura, Mitsuru; Takei, Naoyuki; Matsuda, Tsuyoshi; Sugimura, Kazuro

2007-03-01

To examine the possibility of using a 3 Tesla (T) magnetic resonance (MR) scanner with a custom-made external coil to obtain ductal details of the prostate, high-quality spectra, and metabolite mapping corresponding to prostate zonal anatomy in healthy volunteers. MRI and two-dimensional (2D) chemical shift imaging (CSI) were performed in 16 healthy volunteers using a 3T scanner with a custom-made external transmit-receive (transceive) coil. Visualization of the prostatic duct-like structure was analyzed on T2-weighted (T2W) images. The resolution of the metabolite peaks and the distribution of metabolites in CSI were also assessed. In the axial plane, 3-mm-thick images were better than 4-mm-thick images with the same voxel volume for assessing duct-like structures and prostatic urethra. Differentiation between inner and outer citrate (Cit) peaks was frequently observed (29 out of 30). The mean peak area ratio of choline (Cho) plus creatine (Cr) over Cit in the peripheral zone (PZ) was significantly lower than in the transition zone (TZ) (P = 0.014). 3T MR examinations of the prostate using an external coil allow information to be collected about the details of duct-like structures, the high-quality spectra of Cit, and the zone-specific distribution of metabolites.

Testing of TAMU3: a Nb 3Sn Block–Coil Dipole with Stress Management

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

McIntyre, Peter

The Accelerator Research Lab (ARL) at Texas A&M has recently concluded the construction and testing of a superconducting block-coil dipole TAMU3. TAMU3 reached 85% of the resistive-onset short sample critical current (0.1 μV/cm criterion) that was measured on extracted strands at the National High Magnetic Field Lab. Peak magnet current was 6603 amps, and all with quenches originated in the vicinity of the hard-way chicane near the exit lead of the TAMU3c inner winding. Leading up to the testing we discovered that we had made two grievous mistakes in the fabrication (we mistakenly used the wrong superconducting wire for themore » cables of the inner windings) and the heat treatment (we used a heat treatment that was too hot and too long). We extracted strands from the leads of the inner and outer windings, and colleagues at NHMFL performed short-sample measurements upon them. The NHMFL measurements indicated RRR ~ 2-5, which gives very little stability against microquenches. The short-sample tests of the extracted strands exhibited a long resistive transition, in which there was a current I sc(B) beyond which it became resistive, then a higher current In(B) at which it went fully normal. Using the I sc(B) data we predicted a short-sample limit for the revised load line of TAMU3 of 7700 A (9 T) – a disappointing reduction from the 14 T objective. On those unhappy notes we undertook the testing of the dipole. The first quench occurred at 5695 A, and the dipole trained thereafter to a maximum quench current of 6600 A (7.6 T), 85% of the compromised short-sample limit. All quenches occurred at a single location, in the region of the S-bend transition and outer lead of one inner winding. Data was collected from stress transducers on the outer windings to evaluate stress management, and on the coil ends to evaluate capture of axial forces by staticfriction lock. The low field reached prevented us from extending those tests to the stress levels where they would have become most interesting, but the designed stress management appeared to be working at the level tested.« less

A mini axial and a permanent maglev radial heart pump.

PubMed

Qian, Kun-Xi; Ru, Wei-Min; Wang, Hao; Jing, Teng

2007-05-31

The implantability and durability have been for decades the focus of artificial heart R&D. A mini axial and a maglev radial pump have been developed to meet with such requirements.The mini axial pump weighing 27g (incl.5g rotor) has an outer diameter of 21mm and a length of 10mm in its largest point, but can produce a maximal blood flow of 6l/min with 50mmHg pressure increase. Therefore, it is suitable for the patients of 40-60kg body weight. For other patients of 60-80kg or 80-100kg body weight, the mini axial pumps of 23mm and 25mm outer diameter had been developed before, these devices were acknowledged to be the world smallest LVADs by Guinness World Record Center in 2004.The permanent maglev radial pump weighing 150g is a shaft-less centrifugal pump with permanent magnetic bearings developed by the author. It needs no second coil for suspension of the rotor except the motor coil, different from all other maglev pumps developed in USA, Japan, European, etc. Thus no detecting and controlling systems as well as no additional power supply for maglev are necessary. The pump can produce a blood flow up to as large as 10l/min against 100mmHg pressure.An implantable and durable blood pump will be a viable alternative to natural donor heart for transplantation.

Integrated Scenario Modeling of NSTX Advanced Plasma Configurations

NASA Astrophysics Data System (ADS)

Kessel, Charles; Synakowski, Edward

2003-10-01

The Spherical Torus will provide an attractive fusion energy source if it can demonstrate the following major features: high elongation and triangularity, 100% non-inductive current with a credible path to high bootstrap fractions, non-solenoidal startup and current rampup, high beta with stabilization of RWM instabilities, and sufficiently high energy confinement. NSTX has specific experimental milestones to examine these features, and integrated scenario modeling is helping to understand how these configurations might be produced and what tools are needed to access this operating space. Simulations with the Tokamak Simulation Code (TSC), CURRAY, and JSOLVER/BALMSC/PEST2 have identified fully non-inductively sustained, high beta plasmas that rely on strong plasma shaping accomplished with a PF coil modification, off-axis current drive from Electron Bernstein Waves (EBW), flexible on-axis heating and CD from High Harmonic Fast Wave (HHFW) and Neutral Beam Injection (NBI), and density control. Ideal MHD stability shows that with wall stabilization through plasma rotation and/or RWM feedback coils, a beta of 40% is achievable, with 100% non-inductive current sustained for 4 current diffusion times. Experimental data and theory are combined to produce a best extrapolation to these regimes, which is continuously improved as the discharges approach these parameters, and theoretical/computational methods expand. Further investigations and development for integrated scenario modeling on NSTX is discussed.

Human auditory system response to pulsed radiofrequency energy in RF coils for magnetic resonance at 2.4 to 170 MHz.

PubMed

Röschmann, P

1991-10-01

The threshold conditions for an auditory perception of pulsed radiofrequency (RF) energy absorption in the human head have been studied on six volunteers with RF coils for magnetic resonance (MR) imaging. For homogeneous RF exposure with MR head coils in the 2.4- to 170-MHz range and pulse widths 3 microseconds less than or equal to Tp less than 100 microseconds, the auditory thresholds were observed at 16 +/- 4 mJ pulse energy. Localized RF exposure with optimized surface coils positioned flush with the ear lowers the auditory threshold to only 3 +/- 0.6 mJ. The hearing threshold of RF pulses with Tp greater than 200 microseconds occurs at more or less constant peak power levels of typically 150 +/- 50 W for head coils and as low as 20 W for surface coils. The results from this study confirm theoretical predictions from a thermoelastic expansion model and compare well with reported thresholds from near field antenna measurements at 425 to 3000 MHz. Details of the threshold dependence on RF pulse length reveal primary sites of RF to acoustic energy conversion at the mastoid and temporal bone region and the outer layer of the brain from where thermoelastically generated pressure transients excite audible pressure waves at the resonance modes of the skull around 1.7 kHz and of the brain around 11 kHz. If not masked by usually dominating noise from switched gradients, the conditions for hearing RF pulses, as applied to head coils in MR studies with flip angle alpha at main field B0, is given by Tp/ms less than or equal to 0.4 (alpha/pi)B0/[T]. At peak power levels up to 15 kW presently available in clinical MR systems, there is no evidence known for detrimental health effects arising from the RF auditory phenomenon which is a secondary cause associated with primary RF to thermal energy conversion in body tissues. To avoid the RF-evoked sound pressure levels in the head rising above the discomfort threshold at 110 dB SPL, an upper limit of 30 kW applied peak pulse power is suggested for head coils and 6 kW for surface coils.

NASA Lewis Research Center combustion MHD experiment

NASA Technical Reports Server (NTRS)

Smith, J. M.

1982-01-01

The MHD power generation experiments were conducted in a high field strength cryomagnet which was adapted from an existing facility. In its original construction, it consisted of 12 high purity aluminum coils pool cooled in a bath of liquid neon. In this configuration, a peak field of 15 tesla was produced. For the present experiments, the center four coils were removed and a 23 cm diameter transverse warm bore tube was inserted to allow the placement of the MHD experiment between the remaining eight coils. In this configuration, a peak field of 6 tesla should be obtainable. The time duration of the experiment is limited by the neon supply which allows on the order of 1 minute of total operating time followed by an 18-hour reliquefaction period. As a result, the experiments are run in a pulsed mode. The run duration for the data presented here was 5 sec. The magnetic field profile along the MHD duct is shown. Since the working fluid is in essence superheated steam, it is easily water quenched at the exit of the diffuser and the components are designed vacuum tight so that the exhaust pipe and demister an be pumped down to simulate the vacuum of outer space.

Consideration of magnetically-induced and conservative electric fields within a loaded gradient coil.

PubMed

Mao, Weihua; Chronik, Blaine A; Feldman, Rebecca E; Smith, Michael B; Collins, Christopher M

2006-06-01

We present a method to calculate the electric (E)-fields within and surrounding a human body in a gradient coil, including E-fields induced by the changing magnetic fields and "conservative" E-fields originating with the scalar electrical potential in the coil windings. In agreement with previous numerical calculations, it is shown that magnetically-induced E-fields within the human body show no real concentration near the surface of the body, where nerve stimulation most often occurs. Both the magnetically-induced and conservative E-fields are shown to be considerably stronger just outside the human body than inside it, and under some circumstances the conservative E-fields just outside the body can be much larger than the magnetically-induced E-fields there. The order of gradient winding and the presence of conductive RF shield can greatly affect the conservative E-field distribution in these cases. Though the E-fields against the outer surface of the body are not commonly considered, understanding gradient E-fields may be important for reasons other than peripheral nerve stimulation (PNS), such as potential interaction with electrical equipment. Copyright 2006 Wiley-Liss, Inc.

Closed loop control of the induction heating process using miniature magnetic sensors

DOEpatents

Bentley, Anthony E.; Kelley, John Bruce; Zutavern, Fred J.

2003-05-20

A method and system for providing real-time, closed-loop control of the induction hardening process. A miniature magnetic sensor located near the outer surface of the workpiece measures changes in the surface magnetic field caused by changes in the magnetic properties of the workpiece as it heats up during induction heating (or cools down during quenching). A passive miniature magnetic sensor detects a distinct magnetic spike that appears when the saturation field, B.sub.sat, of the workpiece has been exceeded. This distinct magnetic spike disappears when the workpiece's surface temperature exceeds its Curie temperature, due to the sudden decrease in its magnetic permeability. Alternatively, an active magnetic sensor can measure changes in the resonance response of the monitor coil when the excitation coil is linearly swept over 0-10 MHz, due to changes in the magnetic permeability and electrical resistivity of the workpiece as its temperature increases (or decreases).

Use of miniature magnetic sensors for real-time control of the induction heating process

DOEpatents

Bentley, Anthony E.; Kelley, John Bruce; Zutavern, Fred J.

2002-01-01

A method of monitoring the process of induction heating a workpiece. A miniature magnetic sensor located near the outer surface of the workpiece measures changes in the surface magnetic field caused by changes in the magnetic properties of the workpiece as it heats up during induction heating (or cools down during quenching). A passive miniature magnetic sensor detects a distinct magnetic spike that appears when the saturation field, B.sub.sat, of the workpiece has been exceeded. This distinct magnetic spike disappears when the workpiece's surface temperature exceeds its Curie temperature, due to the sudden decrease in its magnetic permeability. Alternatively, an active magnetic sensor can also be used to measure changes in the resonance response of the monitor coil when the excitation coil is linearly swept over 0-10 MHz, due to changes in the magnetic permeability and electrical resistivity of the workpiece as its temperature increases (or decreases).

Development of fast cooling pulsed magnets at the Wuhan National High Magnetic Field Center.

PubMed

Peng, Tao; Sun, Quqin; Zhao, Jianlong; Jiang, Fan; Li, Liang; Xu, Qiang; Herlach, Fritz

2013-12-01

Pulsed magnets with fast cooling channels have been developed at the Wuhan National High Magnetic Field Center. Between the inner and outer sections of a coil wound with a continuous length of CuNb wire, G10 rods with cross section 4 mm × 5 mm were inserted as spacers around the entire circumference, parallel to the coil axis. The free space between adjacent rods is 6 mm. The liquid nitrogen flows freely in the channels between these rods, and in the direction perpendicular to the rods through grooves provided in the rods. For a typical 60 T pulsed magnetic field with pulse duration of 40 ms, the cooling time between subsequent pulses is reduced from 160 min to 35 min. Subsequently, the same technology was applied to a 50 T magnet with 300 ms pulse duration. The cooling time of this magnet was reduced from 480 min to 65 min.

Instrumentation for cryogenic magic angle spinning dynamic nuclear polarization using 90 L of liquid nitrogen per day

NASA Astrophysics Data System (ADS)

Albert, Brice J.; Pahng, Seong Ho; Alaniva, Nicholas; Sesti, Erika L.; Rand, Peter W.; Saliba, Edward P.; Scott, Faith J.; Choi, Eric J.; Barnes, Alexander B.

2017-10-01

Cryogenic sample temperatures can enhance NMR sensitivity by extending spin relaxation times to improve dynamic nuclear polarization (DNP) and by increasing Boltzmann spin polarization. We have developed an efficient heat exchanger with a liquid nitrogen consumption rate of only 90 L per day to perform magic-angle spinning (MAS) DNP experiments below 85 K. In this heat exchanger implementation, cold exhaust gas from the NMR probe is returned to the outer portion of a counterflow coil within an intermediate cooling stage to improve cooling efficiency of the spinning and variable temperature gases. The heat exchange within the counterflow coil is calculated with computational fluid dynamics to optimize the heat transfer. Experimental results using the novel counterflow heat exchanger demonstrate MAS DNP signal enhancements of 328 ± 3 at 81 ± 2 K, and 276 ± 4 at 105 ± 2 K.

METAL RESISTIVITY MEASURING DEVICE

DOEpatents

Renken, J. Jr.; Myers, R.G.

1960-12-20

An eddy current device is offered for detecting discontinuities in metal samples. Alternate short and long duration pulses are inductively applied to a metal sample via the outer coil of a probe. The long pulses give a resultant signal from the metal sample responsive to probe-tosample spacing and discontinuities within the sample and the shont pulses give a resultant signal responsive only to probe -to-sample spacing. The inner coil of the probe detects the two resultant signals and transmits them to a separation network where the two signals are separated. The two separated signals are then transmitted to a compensation network where the detected signals due to the short pulses are used to compensate for variations due to probe-to-sample spacing contained in the detected signals from the long pulses. Thus, a resultant signal is obtained responsive to discontinuities within the sample and independent of probe-to- sample spacing.

Design of Diaphragm and Coil for Stable Performance of an Eddy Current Type Pressure Sensor.

PubMed

Lee, Hyo Ryeol; Lee, Gil Seung; Kim, Hwa Young; Ahn, Jung Hwan

2016-07-01

The aim of this work was to develop an eddy current type pressure sensor and investigate its fundamental characteristics affected by the mechanical and electrical design parameters of sensor. The sensor has two key components, i.e., diaphragm and coil. On the condition that the outer diameter of sensor is 10 mm, two key parts should be designed so as to keep a good linearity and sensitivity. Experiments showed that aluminum is the best target material for eddy current detection. A round-grooved diaphragm is suggested in order to measure more precisely its deflection caused by applied pressures. The design parameters of a round-grooved diaphragm can be selected depending on the measuring requirements. A developed pressure sensor with diaphragm of t = 0.2 mm and w = 1.05 mm was verified to measure pressure up to 10 MPa with very good linearity and errors of less than 0.16%.

Metal Resistivity Measuring Device

DOEpatents

Renken, Jr, C. J.; Myers, R. G.

1960-12-20

An eddy current device is designed for detecting discontinuities in metal samples. Alternate short and long duration pulses are inductively applied to a metal sample via the outer coil of a probe. The lorg pulses give a resultant signal from the metal sample responsive to probe-tosample spacing and discontinuities with the sample, and the short pulses give a resultant signal responsive only to probe-to-sample spacing. The inner coil of the probe detects the two resultant signals and transmits them to a separation network where the two signals are separated. The two separated signals are then transmitted to a compensation network where the detected signals due to the short pulses are used to compensate for variations due to probeto-sample spacing contained in the detected signals from the long pulses. Thus a resultant signal is obtained responsive to discontinuities within the sample and independent of probe-to- sample spacing.

Predictive Power-balance Modeling of PEGASUS and NSTX-U Local Helicity Injection Discharges

NASA Astrophysics Data System (ADS)

Barr, J. L.; Bongard, M. W.; Burke, M. G.; Fonck, R. J.; Hinson, E. T.; Perry, J. M.; Redd, A. J.; Schlossberg, D. J.

2013-10-01

Local helicity injection (LHI) with outer poloidal-field (PF) induction for solenoid-free startup is being studied on PEGASUS, reaching Ip <= 0 . 175 MA with 6 kA of injected current. A lumped-parameter circuit model for predicting the performance of LHI initiated plasmas is under development. The model employs energy and helicity balance, and includes applied PF ramping and the inductive effects of shape evolution. Low- A formulations for both the plasma external inductance and a uniform equilibrium-field are used to estimate inductive voltages. PEGASUS LHI plasmas are created near the outboard injectors with aspect ratio (A) ~ 5-6.5 and grow inward to fill the confinement region at A <= 1 . 3 . Initial results match experimental Ip (t) trajectories within 15 kA with a prescribed geometry evolution. Helicity injection is the largest driving term in the initial phase, but in the later phase is reduced to 20-45% of the total drive as PF induction and decreasing plasma inductance become dominant. In contrast, attaining ~1 MA non-solenoidal startup via LHI on NSTX-U will require operation in the regime where helicity injection drive exceeds inductive and geometric changes at full size. A large-area multi-injector array will increase available helicity injection by 3-4 times and allow exploration of this helicity-dominated regime at Ip ~ 0 . 3 MA in PEGASUS. Comparison of model predictions with time-evolving magnetic equilibria is in progress for model validation. Work supported by US DOE Grant DE-FG02-96ER54375.

Lithostratigraphy, biostratigraphy and chemostratigraphy of Upper Cretaceous and Paleogene sediments from southern Tanzania: Tanzania Drilling Project Sites 27-35

NASA Astrophysics Data System (ADS)

Jimènez Berrocoso, Àlvaro; Huber, Brian T.; MacLeod, Kenneth G.; Petrizzo, Maria Rose; Lees, Jacqueline A.; Wendler, Ines; Coxall, Helen; Mweneinda, Amina K.; Falzoni, Francesca; Birch, Heather; Singano, Joyce M.; Haynes, Shannon; Cotton, Laura; Wendler, Jens; Bown, Paul R.; Robinson, Stuart A.; Gould, Jeremy

2012-07-01

The 2008 Tanzania Drilling Project (TDP) expedition recovered common planktonic foraminifera (PF), calcareous nannofossils (CN) and calcareous dinoflagellates with extraordinary shell preservation at multiple Cenomanian-Campanian sites that will be used for paleoclimatic, paleoceanographic, and biostratigraphic studies. New cores confirm the existence of a more expanded and continuous Upper Cretaceous sequence than had previously been documented in the Lindi and Kilwa regions of southeastern coastal Tanzania. This TDP expedition cored 684.02 m at eight Upper Cretaceous sites (TDP Sites 28-35) and a thin Paleocene section (TDP Site 27). TDP Sites 29, 30, 31 and 34 together span the lowermost Turonian to Coniacian (PF Whiteinella archaeocretacea to Dicarinella concavata Zones and CN Zones UC6a-9b), with TDP Site 31 being the most biostratigraphically complete Turonian section found during TDP drilling. A discontinuous section from the Santonian-upper Campanian (PF D. asymetrica to Radotruncana calcarata Zones and CN Zones UC12-16) was collectively recovered at TDP Sites 28, 32 and 35, while thin sequences of the lower Cenomanian (PF Thalmanninella globotruncanoides Zone and CN subzones UC3a-b) and middle Paleocene (Selandian; PF Zone P3a and CN Zone NP5) were cored in TDP Sites 33 and 27, respectively. Records of δ13Corg and δ13Ccarb from bulk sediments generated for all the Cretaceous sites show largely stable values through the sections. Only a few parallel δ13Corg and δ13Ccarb shifts have been found and they are interpreted to reflect local processes. The δ18Ocarb record, however, is consistent with Late Cretaceous cooling trends from the Turonian into the Campanian. Lithologies of these sites include thick intervals of claystones and siltstones with locally abundant, finely-laminated fabrics, irregular occurrences of thin sandstone layers, and sporadic bioclastic debris (e.g., inoceramids, ammonites). Minor lithologies represent much thinner units of up to medium-grained, massive sandstones. The %CaCO3 (∼5-40%) and %Corg (∼0.1-2%) are variable, with the highest %CaCO3 in the lower Campanian and the highest %Corg in the Turonian. Lithofacies analysis suggests that deposition of these sediments occurred in outer shelf-upper slope, a setting that agrees well with inferences from benthic foraminifera and calcareous dinoflagellates.

3D-Analysis of a non-planispiral ammonoid from the Hunsrück Slate: natural or pathological variation?

PubMed Central

Stilkerich, Julia; Smrecak, Trisha A.

2017-01-01

We herein examine the only known non-planispirally coiled early Devonian ammonoid, the holotype specimen of Ivoites opitzi, to investigate if the host was encrusted in vivo and if these sclerobionts were responsible for the trochospiral coiling observed in this unique specimen. To test if the presence of runner-like sclerobionts infested the historically collected specimen of Ivoites opitzi during its life, we used microCT to produce a three-dimensional model of the surface of the specimen. Our results indicate that sclerobionts grew across the outer rim (venter) on both sides of the ammonoid conch at exactly the location where the deviation from the planispiral was recognized, and where subsequent ammonoid growth would likely preclude encrustation. This indicates in vivo encrustation of the I. opitzi specimen, and represents the earliest documentation of the phenomenon. Further, this suggests that non-planispiral coiling in I. opitzi was likely pathologically induced and does not represent natural morphological variation in the species. Despite the observed anomalies in coiling, the specimen reached adulthood and retains important identifying morphological features, suggesting the ammonoid was minimally impacted by encrustation in life. As such, appointing a new type specimen—as suggested by some authors—for the species is not necessary. In addition, we identify the sclerobionts responsible for modifying the coiling of this specimen as hederelloids, a peculiar group of sclerobionts likely related to phoronids. Hederelloids in the Devonian are commonly found encrusting on fossils collected in moderately deep environments within the photic zone and are rarely documented in dysphotic and aphotic samples. This indicates that when the ammonoid was encrusted it lived within the euphotic zone and supports the latest interpretations of the Hunsrück Slate depositional environment in the Bundenbach-Gemünden area. PMID:28674668

High Radiation Environment Nuclear Fragment Separator Magnet

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

Kahn, Stephen; Gupta, Ramesh

2016-01-31

Superconducting coils wound with HTS conductor can be used in magnets located in a high radiation environment. NbTi and Nb 3Sn superconductors must operate at 4.5 K or below where removal of heat is less efficient. The HTS conductor can carry significant current at higher temperatures where the Carnot efficiency is significantly more favorable and where the coolant heat capacity is much larger. Using the HTS conductor the magnet can be operated at 40 K. This project examines the use of HTS conductor for the Michigan State University Facility For Rare Isotope Beams (FRIB) fragment separator dipole magnet which bendsmore » the beam by 30° and is located in a high radiation region that will not be easily accessible. Two of these magnets are needed to select the chosen isotope. There are a number of technical challenges to be addressed in the design of this magnet. The separator dipole is 2 m long and subtends a large angle. The magnet should keep a constant transverse field profile along its beam reference path. Winding coils with a curved inner segment is difficult as the conductor will tend to unwind during the process. In the Phase I project two approaches to winding the conductor were examined. The first was to wind the coils with curved sections on the inner and outer segments with the inner segment wound with negative curvature. The alternate approach was to use a straight segment on the inner segment to avoid negative curvature. In Phase I coils with a limited number of turns were successfully wound and tested at 77 K for both coil configurations. The Phase II program concentrated on the design, coil winding procedures, structural analysis, prototyping and testing of an HTS curved dipole coil at 40 K with a heat load representative of the radiation environment. One of the key criteria of the design of this magnet is to avoid the use of organic materials that would degrade rapidly in radiation. The Lorentz forces expected from the coils interacting with the magnetic field are large and in order minimize the deformation of the coils, mechanical support must be provided. Since the support structure cannot be made of organic materials with minimal thermal conductivity, an optimization was explored comparing the amount of coil deformation that can be tolerated and the amount of heat leakage that can be endured. A test coil containing 500 m of HTS was constructed to be tested at the 40 K operating temperature. The anticipated heat load was simulated with heater strips to demonstrate that the heat could be removed and that the coil can operate in a stable state. The FRIB project has decided that using HTS coils for this magnet was too risky considering their time and funding constraints and has opted for a more conservative approach with conventional coils. As an outcome of this STTR project, it is likely that HTS coils operating at higher temperatures will have beneficial applications for future accelerator projects.« less

Self-calibrated correlation imaging with k-space variant correlation functions.

PubMed

Li, Yu; Edalati, Masoud; Du, Xingfu; Wang, Hui; Cao, Jie J

2018-03-01

Correlation imaging is a previously developed high-speed MRI framework that converts parallel imaging reconstruction into the estimate of correlation functions. The presented work aims to demonstrate this framework can provide a speed gain over parallel imaging by estimating k-space variant correlation functions. Because of Fourier encoding with gradients, outer k-space data contain higher spatial-frequency image components arising primarily from tissue boundaries. As a result of tissue-boundary sparsity in the human anatomy, neighboring k-space data correlation varies from the central to the outer k-space. By estimating k-space variant correlation functions with an iterative self-calibration method, correlation imaging can benefit from neighboring k-space data correlation associated with both coil sensitivity encoding and tissue-boundary sparsity, thereby providing a speed gain over parallel imaging that relies only on coil sensitivity encoding. This new approach is investigated in brain imaging and free-breathing neonatal cardiac imaging. Correlation imaging performs better than existing parallel imaging techniques in simulated brain imaging acceleration experiments. The higher speed enables real-time data acquisition for neonatal cardiac imaging in which physiological motion is fast and non-periodic. With k-space variant correlation functions, correlation imaging gives a higher speed than parallel imaging and offers the potential to image physiological motion in real-time. Magn Reson Med 79:1483-1494, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

A Mini Axial and a Permanent Maglev Radial Heart Pump§

PubMed Central

Qian, Kun-Xi; Ru, Wei-Min; Wang, Hao; Jing, Teng

2007-01-01

The implantability and durability have been for decades the focus of artificial heart R&D. A mini axial and a maglev radial pump have been developed to meet with such requirements. The mini axial pump weighing 27g (incl.5g rotor) has an outer diameter of 21mm and a length of 10mm in its largest point, but can produce a maximal blood flow of 6l/min with 50mmHg pressure increase. Therefore, it is suitable for the patients of 40-60kg body weight. For other patients of 60-80kg or 80-100kg body weight, the mini axial pumps of 23mm and 25mm outer diameter had been developed before, these devices were acknowledged to be the world smallest LVADs by Guinness World Record Center in 2004. The permanent maglev radial pump weighing 150g is a shaft-less centrifugal pump with permanent magnetic bearings developed by the author. It needs no second coil for suspension of the rotor except the motor coil, different from all other maglev pumps developed in USA, Japan, European, etc. Thus no detecting and controlling systems as well as no additional power supply for maglev are necessary. The pump can produce a blood flow up to as large as 10l/min against 100mmHg pressure. An implantable and durable blood pump will be a viable alternative to natural donor heart for transplantation. PMID:19662120

NH NMR shifts of new structurally characterized fac-[Re(CO)3(polyamine)]n+ complexes probed via outer-sphere hydrogen-bonding interactions to anions, including the paramagnetic [Re(IV)Br6]2- anion.

PubMed

Perera, Theshini; Marzilli, Patricia A; Fronczek, Frank R; Marzilli, Luigi G

2010-06-21

fac-[Re(I)(CO)(3)L](n) complexes serve as models for short-lived fac-[(99m)Tc(I)(CO)(3)L](n) imaging tracers (L = tridentate ligands forming two five-membered chelate rings defining the L face). Dangling groups on L, needed to achieve desirable biodistribution, complicate the NMR spectra, which are not readily understood. Using less complicated L, we found that NH groups (exo-NH) projecting toward the L face sometimes showed an upfield shift attributable to steric shielding of the exo-NH group from the solvent by the chelate rings. Our goal is to advance our ability to relate these spectral features to structure and solution properties. To investigate whether exo-NH groups in six-membered rings exhibit the same effect and whether the presence of dangling groups alters the effect, we prepared new fac-[Re(CO)(3)L](n+) complexes that allow direct comparisons of exo-NH shifts for six-membered versus five-membered chelate rings. New complexes were structurally characterized with the following L: dipn [N-3-(aminopropyl)-1,3-propanediamine], N'-Medipn (3,3'-diamino-N-methyldipropylamine), N,N-Me(2)dipn (N,N-dimethyldipropylenetriamine), aepn [N-2-(aminoethyl)-1,3-propanediamine], trpn [tris-(3-aminopropyl)amine], and tren [tris-(2-aminoethyl)amine]. In DMSO-d(6), the upfield exo-NH signals were exhibited by all complexes, indicating that the rings sterically shield the exo-NH groups from bulky solvent molecules. This interpretation was supported by exo-NH signal shift changes caused by added halide and [ReBr(6)](2-) anions, consistent with outer-sphere hydrogen-bond interactions between these anions and the exo-NH groups. For fac-[Re(CO)(3)(dipn)]PF(6) in acetonitrile-d(3), the exo-NH signal shifted further downfield in the series, Cl(-) > Br(-) > I(-), and the plateau in the shift change required a lower concentration for smaller anions. These results are consistent with steric shielding of the exo-NH groups by the chelate rings. Nevertheless, despite its size, the shape and charge of [ReBr(6)](2-) allowed the dianion to induce large upfield paramagnetic shifts of the exo-NH signal of fac-[Re(CO)(3)(dipn)]PF(6). This dianion shows promise as an outer-sphere hydrogen-bonding paramagnetic shift reagent.

Downhole transmission system comprising a coaxial capacitor

DOEpatents

Hall, David R [Provo, UT; Pixton, David S [Lehi, UT; Johnson, Monte L [Orem, UT; Bartholomew, David B [Springville, UT; Hall, Jr., H. Tracy; Rawle, Michael [Springville, UT

2011-05-24

A transmission system in a downhole component comprises a plurality of data transmission elements. A coaxial cable having an inner conductor and an outer conductor is disposed within a passage in the downhole component such that at least one capacitor is disposed in the passage and having a first terminal coupled to the inner conductor and a second terminal coupled to the outer conductor. Preferably the transmission element comprises an electrically conducting coil. Preferably, within the passage a connector is adapted to electrically connect the inner conductor of the coaxial cable and the lead wire. The coaxial capacitor may be disposed between and in electrically communication with the connector and the passage. In another embodiment a connector is adapted to electrical connect a first and a second portion of the inner conductor of the coaxial cable and a coaxial capacitor is in electrical communication with the connector and the passage.

A new quadrature annular resonator for 3 T MRI based on artificial-dielectrics.

PubMed

Mikhailovskaya, Anna A; Shchelokova, Alena V; Dobrykh, Dmitry A; Sushkov, Ivan V; Slobozhanyuk, Alexey P; Webb, Andrew

2018-06-01

Dielectric resonators have previously been constructed for ultra-high frequency magnetic resonance imaging and microscopy. However, it is challenging to design these dielectric resonators at clinical field strengths due to their intrinsically large dimensions, especially when using materials with moderate permittivity. Here we propose and characterize a novel approach using artificial-dielectrics which reduces substantially the required outer diameter of the resonator. For a resonator designed to operate in a 3 Tesla scanner using water as the dielectric, a reduction in outer diameter of 37% was achieved. When used in an inductively-coupled wireless mode, the sensitivity of the artificial-dielectric resonator was measured to be slightly higher than that of a standard dielectric resonator operating in its degenerate circularly-polarized hybrid electromagnetic modes (HEM 11 ). This study demonstrates the first application of an artificial-dielectric approach to MR volume coil design. Copyright © 2018 Elsevier Inc. All rights reserved.

A new quadrature annular resonator for 3 T MRI based on artificial-dielectrics

NASA Astrophysics Data System (ADS)

Mikhailovskaya, Anna A.; Shchelokova, Alena V.; Dobrykh, Dmitry A.; Sushkov, Ivan V.; Slobozhanyuk, Alexey P.; Webb, Andrew

2018-06-01

Dielectric resonators have previously been constructed for ultra-high frequency magnetic resonance imaging and microscopy. However, it is challenging to design these dielectric resonators at clinical field strengths due to their intrinsically large dimensions, especially when using materials with moderate permittivity. Here we propose and characterize a novel approach using artificial-dielectrics which reduces substantially the required outer diameter of the resonator. For a resonator designed to operate in a 3 Tesla scanner using water as the dielectric, a reduction in outer diameter of 37% was achieved. When used in an inductively-coupled wireless mode, the sensitivity of the artificial-dielectric resonator was measured to be slightly higher than that of a standard dielectric resonator operating in its degenerate circularly-polarized hybrid electromagnetic modes (HEM11). This study demonstrates the first application of an artificial-dielectric approach to MR volume coil design.

Measurement of tokamak error fields using plasma response and its applicability to ITER

DOE PAGES

Strait, Edward J.; Buttery, Richard J.; Casper, T. A.; ...

2014-04-17

The nonlinear response of a low-beta tokamak plasma to non-axisymmetric fields offers an alternative to direct measurement of the non-axisymmetric part of the vacuum magnetic fields, often termed “error fields”. Possible approaches are discussed for determination of error fields and the required current in non-axisymmetric correction coils, with an emphasis on two relatively new methods: measurement of the torque balance on a saturated magnetic island, and measurement of the braking of plasma rotation in the absence of an island. The former is well suited to ohmically heated discharges, while the latter is more appropriate for discharges with a modest amountmore » of neutral beam heating to drive rotation. Both can potentially provide continuous measurements during a discharge, subject to the limitation of a minimum averaging time. The applicability of these methods to ITER is discussed, and an estimate is made of their uncertainties in light of the specifications of ITER’s diagnostic systems. Furthermore, the use of plasma response-based techniques in normal ITER operational scenarios may allow identification of the error field contributions by individual central solenoid coils, but identification of the individual contributions by the outer poloidal field coils or other sources is less likely to be feasible.« less

A droplet-based passive force sensor for remote tactile sensing applications

NASA Astrophysics Data System (ADS)

Nie, Baoqing; Yao, Ting; Zhang, Yiqiu; Liu, Jian; Chen, Xinjian

2018-01-01

A droplet-based flexible wireless force sensor has been developed for remote tactile-sensing applications. By integration of a droplet-based capacitive sensing unit and two circular planar coils, this inductor-capacitor (LC) passive sensor offers a platform for the mechanical force detection in a wireless transmitting mode. Under external loads, the membrane surface of the sensor deforms the underlying elastic droplet uniformly, introducing a capacitance response in tens of picofarads. The LC circuit transduces the applied force into corresponding variations of its resonance frequency, which is detected by an external electromagnetic coupling coil. Specifically, the liquid droplet features a mechanosensitive plasticity, which results in an increased device sensitivity as high as 2.72 MHz N-1. The high dielectric property of the droplet endows our sensor with high tolerance for noise and large capacitance values (20-40 pF), the highest value in the literature for the LC passive devices in comparable dimensions. It achieves excellent reproducibility under periodical loads ranging from 0 to 1.56 N and temperature fluctuations ranging from 10 °C to 55 °C. As an interesting conceptual demonstration, the flexible device has been configured into a fingertip-amounted setting in a highly compact package (of 11 mm × 11 mm × 0.25 mm) for remote contact force sensing in the table tennis game.

A secretory multifunctional serine protease, DegP of Plasmodium falciparum, plays an important role in thermo-oxidative stress, parasite growth and development.

PubMed

Sharma, Shweta; Jadli, Mohit; Singh, Anu; Arora, Kavita; Malhotra, Pawan

2014-03-01

Plasmodium falciparum heat shock proteins and proteases are known for their indispensable roles in parasite virulence and survival in the host cell. They neutralize various host-derived stress responses that are deleterious for parasite growth and invasion. We report identification and functional characterization of the first DegP from an apicomplexan (P. falciparum). To determine the molecular identity and functions of the parasite-encoded DegP, we complemented the Escherichia coli degP null mutant with a putative PfdegP gene, and the results showed that PfDegP complements the growth defect of the temperature sensitive DegP-deficient mutant and imparts resistance to non-permissive temperatures and oxidative stress. Molecular interaction studies showed that PfDegP exists as a complex with parasite-encoded heat shock protein 70, iron superoxide dismutase and enolase. DegP expression is significantly induced in parasite culture upon heat shock/oxidative stress. Our data suggest that the PfDegP protein may play a role in the growth and development of P. falciparum through its ability to confer protection against thermal/oxidative stress. Antibody against DegP showed anti-plasmodial activity against blood-stage parasites in vitro, suggesting that PfDegP and its associated complex may be a potential focus for new anti-malarial therapies. ●PfDegP physically interacts with PfHsp70 and PfEno by anti-bait co-immunoprecipitation (View interaction) ●PfDegP physically interacts with PfEno, PfSod, PfOat, PfHsp70, PfLDH and PfGpi by anti-bait co-immunoprecipitation (View interaction) ●PfHsp-70 and PfDegP co-localize by fluorescence microscopy (View interaction) ●PfDegP physically interacts with PfOat, PfHsp70, PfEno, PfSod, PfGpi and PfLDH by surface plasmon resonance (View interaction) ●PfEno and PfDegP co-localize by fluorescence microscopy (View interaction) ●PfDegP and PfHsp70 co-localize by co-sedimentation through density gradient (View interaction). © 2014 FEBS.

A dual RF resonator system for high-field functional magnetic resonance imaging of small animals.

PubMed

Ludwig, R; Bodgdanov, G; King, J; Allard, A; Ferris, C F

2004-01-30

A new apparatus has been developed that integrates an animal restrainer arrangement for small animals with an actively tunable/detunable dual radio-frequency (RF) coil system for in vivo anatomical and functional magnetic resonance imaging of small animals at 4.7 T. The radio-frequency coil features an eight-element microstrip line configuration that, in conjunction with a segmented outer copper shield, forms a transversal electromagnetic (TEM) resonator structure. Matching and active tuning/detuning is achieved through fixed/variable capacitors and a PIN diode for each resonator element. These components along with radio-frequency chokes (RFCs) and blocking capacitors are placed on two printed circuit boards (PCBs) whose copper coated ground planes form the front and back of the volume coil and are therefore an integral part of the resonator structure. The magnetic resonance signal response is received with a dome-shaped single-loop surface coil that can be height-adjustable with respect to the animal's head. The conscious animal is immobilized through a mechanical arrangement that consists of a Plexiglas body tube and a head restrainer. This restrainer has a cylindrical holder with a mouthpiece and position screws to receive and restrain the head of the animal. The apparatus is intended to perform anatomical and functional magnetic resonance imaging in conscious animals such as mice, rats, hamsters, and marmosets. Cranial images acquired from fully conscious rats in a 4.7 T Bruker 40 cm bore animal scanner underscore the feasibility of this approach and bode well to extend this system to the imaging of other animals.

LINC Complexes Form by Binding of Three KASH Peptides to Domain Interfaces of Trimeric SUN Proteins

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

Sosa, Brian A.; Rothballer, Andrea; Kutay, Ulrike

Linker of nucleoskeleton and cytoskeleton (LINC) complexes span the nuclear envelope and are composed of KASH and SUN proteins residing in the outer and inner nuclear membrane, respectively. LINC formation relies on direct binding of KASH and SUN in the perinuclear space. Thereby, molecular tethers are formed that can transmit forces for chromosome movements, nuclear migration, and anchorage. We present crystal structures of the human SUN2-KASH1/2 complex, the core of the LINC complex. The SUN2 domain is rigidly attached to a trimeric coiled coil that prepositions it to bind three KASH peptides. The peptides bind in three deep and expansivemore » grooves formed between adjacent SUN domains, effectively acting as molecular glue. In addition, a disulfide between conserved cysteines on SUN and KASH covalently links both proteins. The structure provides the basis of LINC complex formation and suggests a model for how LINC complexes might arrange into higher-order clusters to enhance force-coupling.« less

Experimental and numerical analysis on aluminum/steel pipe using magnetic pulse welding

NASA Astrophysics Data System (ADS)

Shim, J. Y.; Kim, I. S.; Lee, K. J.; Kang, B. Y.

2011-12-01

Recently, there has been a trend in the automotive industry to focus on the improvement of lightweight materials, such as aluminum and magnesium because the welding of dissimilar metals causes many welding defects. Magnetic pulse welding (MPW), one of the solid state welding technologies, uses electromagnetic force from current discharged through a working coil which develops a repulsive force between the induced currents flowing parallel and in the opposite direction in the tube to be welded. The objective of this paper is to develop a numerical model for analysis of the interaction between the outer pipe and the working coil using a finite element method (FEM) in the MPW process. Four Maxwell equations are solved using a general electromagnetic mechanics computer program, ANSYS/EMAG code. Experiments were also carried out with a W-MPW60 machine manufactured by WELMATE CO., LTD. with the Al1070 and SM45C for Al pipe and steel bar respectively. The calculated and measured results were compared to verify the proposed model.

Thermo-hydraulic analysis of the cool-down of the EDIPO test facility

NASA Astrophysics Data System (ADS)

Lewandowska, Monika; Bagnasco, Maurizio

2011-09-01

The first cool-down of the EDIPO (European DIPOle) test facility is foreseen to take place in 2011 by means of the existing 1.2 kW cryoplant at EPFL-CRPP Villigen. In this work, the thermo-hydraulic analysis of the EDIPO cool-down is performed in order both to assess the its duration and to optimize the procedure. The cool-down is driven by the helium flowing in both the outer cooling channel and in the windings connected hydraulically in parallel. We take into account limitations due to the pressure drop in the cooling circuit and the refrigerator capacity as well as heat conduction in the iron yoke. Two schemes of the hydraulic cooling circuit in the EDIPO windings are studied (coils connected in series and coils connected in parallel). The analysis is performed by means of an analytical model complemented by and numerical model. The results indicate that the cool-down to 5 K can be achieved in about 12 days.

Combined hysteroscopy-laparoscopy approach for excision of pelvic nitinol fragment from Essure contraceptive device: Role of intraoperative fluoroscopy for uterine conservation

PubMed Central

Palermo, Gianpiero D.

2016-01-01

We describe the successful removal of a pelvic contraceptive coil in a symptomatic 46-year-old patient who had Essure devices for four years, using a combined hysteroscopy-laparoscopy-fluoroscopy approach. Following normal hysteroscopy, at laparoscopy the right Essure implant was disrupted and its outer nitinol coil had perforated the fallopian tube. However, the inner rod (containing polyethylene terephthalate) had migrated to an extrapelvic location, near the proximal colon. In contrast, the left implant was situated within the corresponding tube. Intraoperative fluoroscopy was used to confirm complete removal of the device, which was further verified by postoperative computed tomography. The patient's condition improved after surgery and she continues to do well. This is the first report to describe this technique in managing Essure complications remote from time of insertion. Our case highlights the value and limitations of preoperative and intraoperative imaging to map Essure fragment location before surgery. PMID:27462605

Design and Testing of a Small Inductive Pulsed Plasma Thruster

NASA Technical Reports Server (NTRS)

Martin, Adam K.; Dominguez, Alexandra; Eskridge, Richard H.; Polzin, Kurt A.; Riley, Daniel P.; Perdue, Kevin A.

2015-01-01

The design and testing of a small inductive pulsed plasma thruster (IPPT) is described. The device was built as a test-bed for the pulsed gas-valves and solid-state switches required for a thruster of this kind, and was designed to be modular to facilitate modification. The thruster in its present configuration consists of a multi-turn, spiral-wound acceleration coil (270 millimeters outer diameter, 100 millimeters inner diameter) driven by a 10 microfarad capacitor and switched with a high-voltage thyristor, a propellant delivery system including a fast pulsed gas-valve, and a glow-discharge pre-ionizer circuit. The acceleration coil circuit may be operated at voltages up to 4 kilovolts (the thyristor limit is 4.5 kilovolts) and the thruster operated at cyclic-rates up to 30 Herz. Initial testing of the thruster, both bench-top and in-vacuum, has been performed. Cyclic operation of the complete device was demonstrated (at 2 Herz), and a number of valuable insights pertaining to the design of these devices have been gained.

CCDC103 mutations cause primary ciliary dyskinesia by disrupting assembly of ciliary dynein arms

PubMed Central

Panizzi, Jennifer R.; Becker-Heck, Anita; Castleman, Victoria H.; Al-Mutairi, Dalal; Liu, Yan; Loges, Niki T.; Pathak, Narendra; Austin-Tse, Christina; Sheridan, Eamonn; Schmidts, Miriam; Olbrich, Heike; Werner, Claudius; Häffner, Karsten; Hellman, Nathan; Chodhari, Rahul; Gupta, Amar; Kramer-Zucker, Albrecht; Olale, Felix; Burdine, Rebecca D.; Schier, Alexander F.; O’Callaghan, Christopher; Chung, Eddie MK; Reinhardt, Richard; Mitchison, Hannah M.; King, Stephen M.; Omran, Heymut; Drummond, Iain A.

2012-01-01

Cilia are essential for fertilization, respiratory clearance, cerebrospinal fluid circulation, and to establish laterality1. Cilia motility defects cause Primary Ciliary Dyskinesia (PCD, MIM 242650), a disorder affecting 1:15-30,000 births. Cilia motility requires the assembly of multisubunit dynein arms that drive cilia bending2. Despite progress in understanding the genetic basis of PCD, mutations remain to be identified for several PCD linked loci3. Here we show that the zebrafish cilia paralysis mutant schmalhanstn222 (smh) mutant encodes the coiled-coil domain containing 103 protein (Ccdc103), a foxj1a regulated gene. Screening 146 unrelated PCD families identified patients in six families with reduced outer dynein arms, carrying mutations in CCDC103. Dynein arm assembly in smh mutant zebrafish was rescued by wild-type but not mutant human CCDC103. Chlamydomonas Ccdc103 functions as a tightly bound, axoneme-associated protein. The results identify Ccdc103 as a novel dynein arm attachment factor that when mutated causes Primary Ciliary Dyskinesia. PMID:22581229

The principle of relativity, superluminality and EPR experiments. "Riserratevi sotto coverta ..."

NASA Astrophysics Data System (ADS)

Cocciaro, B.

2015-07-01

The principle of relativity claims the invariance of the results for experiments carried out in inertial reference frames if the system under examination is not in interaction with the outside world. In this paper it is analysed a model suggested by J. S. Bell, and later developed by P. H. Eberhard, D. Bohm and B. Hiley on the basis of which the EPR correlations would be due to superluminal exchanges between the various parts of the entangled system under examination. In the model the existence of a privileged reference frame (PF) for the propagation of superluminal signals is hypothesized so that these superluminal signals may not give rise to causal paradoxes. According to this model, in an EPR experiment, the entangled system interacts with the outer world since the result of the experiment depends on an entity (the reference frame PF) that is not prepared by the experimenter. The existence of this privileged reference frame makes the model non invariant for Lorentz transformations. In this paper, in opposition to what claimed by the authors mentioned above, the perfect compatibility of the model with the theory of relativity is strongly maintained since, as already said, the principle of relativity does not require that the results of experiments carried out on systems interacting with the outside world should be invariant.

Determination of wood wettability properties of oil palm trunk, Shorea sp. and Paraserianthes falcataria by contact angle method

NASA Astrophysics Data System (ADS)

Sucipto, T.; Hartono, R.; Dwianto, W.

2018-02-01

The aim of this study was to determine the wettability of the inner part of oil palm trunk (OPT), the outer part of OPT, OPT that densified 50%, Shorea sp. and Paraserianthes falcataria wood, as raw material for laminated beams. The wettability of the wood was measured by using cosine-contact angle (CCA) method, which is measuring the angle between dripped resin liquid and the wood surface. The resins that used in this study is phenol formaldehyde (PF) and urea formaldehyde (UF). The results showed that the Shorea sp. and P. falcataria woods have the smallest contact angle or the best wettability properties than OPT. Shorea sp. has the best wettability on PF resin (83.00°), while P. falcataria on UF resin (90.89°), this is due to the levels of starch and extractive substances in Shorea sp. and P. falcataria wood are smaller than OPT. Furthermore, Shorea sp. and P. falcataria wood surfaces are flatter and smoother than OPT, so that the resin will flow easier and wetting the wood surface. In this condition, the liquid resin will flow easier and formed a smaller contact angle. The good wettability of wood will enhance the adhesion properties of laminated beams.

Functional characterization and molecular mechanism exploration of three granulin epithelin precursor splice variants in biomineralization of the pearl oyster Pinctada fucata.

PubMed

Zhao, Mi; He, Maoxian; Huang, Xiande; Wang, Qi; Shi, Yu

2016-02-01

The granulin/epithelin precursor (GEP) encodes a glycoprotein precursor which exhibits pleiotropic tissue growth factor activity with multiple functions. Here, GEP was isolated and its role in the shell biomineralization process of the pearl oyster Pinctada fucata was investigated. Three forms of GEP mRNA were isolated from the pearl oyster (designated PfGEP-1, PfGEP-2 and PfGEP-3). Genomic DNA flanking the splicing region of the PfGEP variants was sequenced and it was found that PfGEP-2 splices out Exon 4, whereas PfGEP-3 splices out Exon 3 compared to PfGEP-1. PfGEP-1 (1505 amino acids) consists of 18 granulin domains, whereas PfGEP-2 (1459 amino acids) and PfGEP-3 (1471 amino acids) consist of 17.5 granulin domains, respectively. Analyses of PfGEP-1 and PfGEP-3 mRNA showed differential patterns in the tissues and developmental stages. Western blotting results showed that the three splice variants can translate to proteins in HEK293T cells. A knockdown experiment using PfGEP dsRNA showed decreased PfGEP-1/PfGEP-3 and PfMSX mRNA, and irregular crystallization of the nacreous layer using scanning electron microscopy. In luciferase assays, co-transfection of PfGEP-1 could activate as well as repress luciferase expression of the reporter plasmid driven by the PfMSX promoter, whereas PfGEP-3 stimulated the expression, elucidating the molecular mechanisms involved in the correlation between PfGEP and PfMSX. These results suggested that GEP variants might function differently during the biomineralization process, which provides new knowledge on the mechanism regulating nacre formation.

Protein-protein interaction studies reveal the Plasmodium falciparum merozoite surface protein-1 region involved in a complex formation that binds to human erythrocytes.

PubMed

Paul, Gourab; Deshmukh, Arunaditya; Kumar Chourasia, Bishwanath; Kalamuddin, Md; Panda, Ashutosh; Kumar Singh, Susheel; Gupta, Puneet K; Mohmmed, Asif; Chauhan, Virender S; Theisen, Michael; Malhotra, Pawan

2018-03-29

Plasmodium falciparum merozoite surface protein (PfMSP) 1 has been studied extensively as a vaccine candidate antigen. PfMSP-1 undergoes proteolytic processing into four major products, such as p83, p30, p38, and p42, that are associated in the form of non-covalent complex(s) with other MSPs. To delineate MSP1 regions involved in the interaction with other MSPs, here we expressed recombinant proteins (PfMSP-1 65 ) encompassing part of p38 and p42 regions and PfMSP-1 19 PfMSP-1 65 interacted strongly with PfMSP-3, PfMSP-6, PfMSP-7, and PfMSP-9, whereas PfMSP-1 19 did not interact with any of these proteins. Since MSP-1 complex binds human erythrocytes, we examined the ability of these proteins to bind human erythrocyte. Among the proteins of MSP-1 complex, PfMSP-6 and PfMSP-9 bound to human erythrocytes. Serological studies showed that PfMSP-1 65 was frequently recognized by sera from malaria endemic regions, whereas this was not the case for PfMSP-1 19 In contrast, antibodies against PfMSP-1 19 showed much higher inhibition of merozoite invasion compared with antibodies against the larger PfMSP-1 65 fragment. Importantly, anti-PfMSP-1 19 antibodies recognized both recombinant proteins, PfMSP-1 19 and PfMSP-1 65 ; however, anti-PfMSP-1 65 antibody failed to recognize the PfMSP-1 19 protein. Taken together, these results demonstrate that PfMSP-1 sequences upstream of the 19 kDa C-terminal region are involved in molecular interactions with other MSPs, and these sequences may probably serve as a smoke screen to evade antibody response to the membrane-bound C-terminal 19 kDa region. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Actin-Cytoskeleton- and Rock-Mediated INM Are Required for Photoreceptor Regeneration in the Adult Zebrafish Retina

PubMed Central

Lahne, Manuela; Li, Jingling; Marton, Rebecca M.

2015-01-01

Loss of retinal neurons in adult zebrafish (Danio rerio) induces a robust regenerative response mediated by the reentry of the resident Müller glia into the cell cycle. Upon initiating Müller glia proliferation, their nuclei migrate along the apicobasal axis of the retina in phase with the cell cycle in a process termed interkinetic nuclear migration (INM). We examined the mechanisms governing this cellular process and explored its function in regenerating the adult zebrafish retina. Live-cell imaging revealed that the majority of Müller glia nuclei migrated to the outer nuclear layer (ONL) to divide. These Müller glia formed prominent actin filaments at the rear of nuclei that had migrated to the ONL. Inhibiting actin filament formation or Rho-associated coiled-coil kinase (Rock) activity, which is necessary for phosphorylation of myosin light chain and actin myosin-mediated contraction, disrupted INM with increased numbers of mitotic nuclei remaining in the basal inner nuclear layer, the region where Müller glia typically reside. Double knockdown of Rho-associated coiled-coil kinase 2a (Rock2a) and Rho-associated coiled-coil kinase 2b (Rock2b) similarly disrupted INM and reduced Müller glial cell cycle reentry. In contrast, Rock inhibition immediately before the onset of INM did not affect Müller glia proliferation, but subsequently reduced neuronal progenitor cell proliferation due to early cell cycle exit. Long-term, Rock inhibition increased the generation of mislocalized ganglion/amacrine cells at the expense of rod and cone photoreceptors. In summary, INM is driven by an actin-myosin-mediated process controlled by Rock2a and Rock2b activity, which is required for sufficient proliferation and regeneration of photoreceptors after light damage. SIGNIFICANCE STATEMENT The human retina does not replace lost or damaged neurons, ultimately causing vision impairment. In contrast, zebrafish are capable of regenerating lost neurons. Understanding the mechanisms that regulate retinal regeneration in these organisms will help to elucidate approaches to stimulate a similar response in humans. In the damaged zebrafish retina, Müller glia dedifferentiate and proliferate to generate neuronal progenitor cells (NPCs) that differentiate into the lost neurons. We show that the nuclei of Müller glia and NPCs migrate apically and basally in phase with the cell cycle. This migration is facilitated by the actin cytoskeleton and Rho-associated coiled-coil kinases (Rocks). We demonstrate that Rock function is required for sufficient proliferation and the regeneration of photoreceptors, likely via regulating nuclear migration. PMID:26609156

Actin-Cytoskeleton- and Rock-Mediated INM Are Required for Photoreceptor Regeneration in the Adult Zebrafish Retina.

PubMed

Lahne, Manuela; Li, Jingling; Marton, Rebecca M; Hyde, David R

2015-11-25

Loss of retinal neurons in adult zebrafish (Danio rerio) induces a robust regenerative response mediated by the reentry of the resident Müller glia into the cell cycle. Upon initiating Müller glia proliferation, their nuclei migrate along the apicobasal axis of the retina in phase with the cell cycle in a process termed interkinetic nuclear migration (INM). We examined the mechanisms governing this cellular process and explored its function in regenerating the adult zebrafish retina. Live-cell imaging revealed that the majority of Müller glia nuclei migrated to the outer nuclear layer (ONL) to divide. These Müller glia formed prominent actin filaments at the rear of nuclei that had migrated to the ONL. Inhibiting actin filament formation or Rho-associated coiled-coil kinase (Rock) activity, which is necessary for phosphorylation of myosin light chain and actin myosin-mediated contraction, disrupted INM with increased numbers of mitotic nuclei remaining in the basal inner nuclear layer, the region where Müller glia typically reside. Double knockdown of Rho-associated coiled-coil kinase 2a (Rock2a) and Rho-associated coiled-coil kinase 2b (Rock2b) similarly disrupted INM and reduced Müller glial cell cycle reentry. In contrast, Rock inhibition immediately before the onset of INM did not affect Müller glia proliferation, but subsequently reduced neuronal progenitor cell proliferation due to early cell cycle exit. Long-term, Rock inhibition increased the generation of mislocalized ganglion/amacrine cells at the expense of rod and cone photoreceptors. In summary, INM is driven by an actin-myosin-mediated process controlled by Rock2a and Rock2b activity, which is required for sufficient proliferation and regeneration of photoreceptors after light damage. The human retina does not replace lost or damaged neurons, ultimately causing vision impairment. In contrast, zebrafish are capable of regenerating lost neurons. Understanding the mechanisms that regulate retinal regeneration in these organisms will help to elucidate approaches to stimulate a similar response in humans. In the damaged zebrafish retina, Müller glia dedifferentiate and proliferate to generate neuronal progenitor cells (NPCs) that differentiate into the lost neurons. We show that the nuclei of Müller glia and NPCs migrate apically and basally in phase with the cell cycle. This migration is facilitated by the actin cytoskeleton and Rho-associated coiled-coil kinases (Rocks). We demonstrate that Rock function is required for sufficient proliferation and the regeneration of photoreceptors, likely via regulating nuclear migration. Copyright © 2015 the authors 0270-6474/15/3515612-23$15.00/0.

Electromagnetic diagnostic system for the Keda Torus eXperiment

NASA Astrophysics Data System (ADS)

Tu, Cui; Liu, Adi; Li, Zichao; Tan, Mingsheng; Luo, Bing; You, Wei; Li, Chenguang; Bai, Wei; Fu, Chenshuo; Huang, Fangcheng; Xiao, Bingjia; Shen, Biao; Shi, Tonghui; Chen, Dalong; Mao, Wenzhe; Li, Hong; Xie, Jinglin; Lan, Tao; Ding, Weixing; Xiao, Chijin; Liu, Wandong

2017-09-01

A system for electromagnetic measurements was designed and installed on the Keda Torus eXperiment (KTX) reversed field pinch device last year. Although the unique double-C structure of the KTX, which allows the machine to be opened easily without disassembling the poloidal field windings, makes the convenient replacement and modification of the internal inductive coils possible, it can present difficulties in the design of flux coils and magnetic probes at the two vertical gaps. Moreover, the KTX has a composite shell consisting of a 6 mm stainless steel vacuum chamber and a 1.5 mm copper shell, which results in limited space for the installation of saddle sensors. Therefore, the double-C structure and composite shell should be considered, especially during the design and installation of the electromagnetic diagnostic system (EDS). The inner surface of the vacuum vessel includes two types of probes. One type is for the measurement of the global plasma parameters, and the other type is for studying the local behavior of the plasma and operating the new saddle coils. In addition, the probes on the outer surface of the composite shell are used for measurements of eddy currents. Finally, saddle sensors for radial field measurements for feedback control were installed between the conducting shell and the vacuum vessel. The entire system includes approximately 1100 magnetic probes, 14 flux coils, 4 ×26 ×2 saddle sensors, and 16 Rogowski coils. Considering the large number of probes and limited space available in the vacuum vessel, the miniaturization of the probes and optimization of the probe distribution are necessary. In addition, accurate calibration and careful mounting of the probes are also required. The frequency response of the designed magnetic probes is up to 200 kHz, and the resolution is 1 G. The EDS, being spherical and of high precision, is one of the most basic and effective diagnostic tools of the KTX and meets the demands imposed by requirements on basic machine operating information and future studies.

Simple coil-powering techniques for generating 10KA/m alternating magnetic field at multiple frequencies using 0.5KW RF power for magnetic nanoparticle hyperthermia

NASA Astrophysics Data System (ADS)

Piao, Daqing; Sun, Tengfei; Ranjan, Ashish

2017-02-01

Alternating magnetic field (AMF) configurable at a range of frequencies is a critical need for optimization of magnetic nanoparticle based hyperthermia, and for their application in targeted drug delivery. Currently, most commercial AMF devices including induction heaters operate at one factory-fixed frequency, thereby limiting customized frequency configuration required for triggered drug release at mild hyperthermia (40-42°C) and ablations (>55°C). Most AMF devices run as an inductor-capacitor resonance network that could allow AMF frequencies to be changed by changing the capacitor bank or the coil looped with it. When developing AMF inhouse, the most expensive component is usually the RF power amplifier, and arguably the most critical step of building a strong AMF field is impedance-matched coupling of RF power to the coolant-cooled AMF coil. AMF devices running at 10KA/m strength are quite common, but generating AMF at that level of field strength using RF power less than 1KW has remained challenging. We practiced a few techniques for building 10KA/m AMFs at different frequencies, by utilizing a 0.5KW 80-800KHz RF power amplifier. Among the techniques indispensable to the functioning of these AMFs, a simple cost-effective technique was the tapping methods for discretely or continuously adjusting the position of an RF-input-tap on a single-layer or the outer-layer of a multi-layer AMF coil for maximum power coupling into the AMF coil. These in-house techniques when combined facilitated 10KA/m AMF at frequencies of 88.8 KHz and higher as allowed by the inventory of capacitors using 0.5KW RF power, for testing heating of 10-15nm size magnetic particles and on-going evaluation of drug-release by low-level temperature-sensitive liposomes loaded with 15nm magnetic nanoparticles.

The Colletotrichum acutatum species complex

PubMed Central

Damm, U.; Cannon, P.F.; Woudenberg, J.H.C.; Crous, P.W.

2012-01-01

Colletotrichum acutatum is known as an important anthracnose pathogen of a wide range of host plants worldwide. Numerous studies have reported subgroups within the C. acutatum species complex. Multilocus molecular phylogenetic analysis (ITS, ACT, TUB2, CHS-1, GAPDH, HIS3) of 331 strains previously identified as C. acutatum and other related taxa, including strains from numerous hosts with wide geographic distributions, confirmed the molecular groups previously recognised and identified a series of novel taxa. Thirty-one species are accepted, of which 21 have not previously been recognised. Colletotrichum orchidophilum clusters basal to the C. acutatum species complex. There is a high phenotypic diversity within this complex, and some of the species appear to have preferences to specific hosts or geographical regions. Others appear to be plurivorous and are present in multiple regions. In this study, only C. salicis and C. rhombiforme formed sexual morphs in culture, although sexual morphs have been described from other taxa (especially as laboratory crosses), and there is evidence of hybridisation between different species. One species with similar morphology to C. acutatum but not belonging to this species complex was also described here as new, namely C. pseudoacutatum. Taxonomic novelties: New combinations - Colletotrichum limetticola (R.E. Clausen) Damm, P.F. Cannon & Crous, C. lupini (Bondar) Damm, P.F. Cannon & Crous, C. salicis (Fuckel) Damm, P.F. Cannon & Crous. New species - C. acerbum Damm, P.F. Cannon & Crous, C. australe Damm, P.F. Cannon & Crous, C. brisbanense Damm, P.F. Cannon & Crous, C. cosmi Damm, P.F. Cannon & Crous, C. costaricense Damm, P.F. Cannon & Crous, C. cuscutae Damm, P.F. Cannon & Crous, C. guajavae Damm, P.F. Cannon & Crous, C. indonesiense Damm, P.F. Cannon & Crous, C. johnstonii Damm, P.F. Cannon & Crous, C. kinghornii Damm, P.F. Cannon & Crous, C. laticiphilum Damm, P.F. Cannon & Crous, C. melonis Damm, P.F. Cannon & Crous, C. orchidophilum Damm, P.F. Cannon & Crous, C. paxtonii Damm, P.F. Cannon & Crous, C. pseudoacutatum Damm, P.F. Cannon & Crous C. pyricola Damm, P.F. Cannon & Crous, C. rhombiforme Damm, P.F. Cannon & Crous, C. scovillei Damm, P.F. Cannon & Crous, C. sloanei Damm, P.F. Cannon & Crous, C. tamarilloi Damm, P.F. Cannon & Crous, C. walleri Damm, P.F. Cannon & Crous. Typifications: Epitypifications - C. acutatum J.H. Simmonds, C. limetticola (R.E. Clausen) Damm, P.F. Cannon & Crous, C. nymphaeae (Pass.) Aa, C. phormii (Henn.) D.F. Farr & Rossman, C. salicis (Fuckel) Damm, P.F. Cannon & Crous. Lectotypifications - C. nymphaeae (Pass.) Aa, C. orchidearum Allesch. PMID:23136458

In vitro, ex vivo and in vivo characterization of PLGA nanoparticles loading pranoprofen for ocular administration.

PubMed

Cañadas, Cristina; Alvarado, Helen; Calpena, Ana C; Silva, Amélia M; Souto, Eliana B; García, Maria L; Abrego, Guadalupe

2016-09-25

Pranoprofen (PF) is a NSAID considered as a safe anti-inflammatory treatment for strabismus and/or cataract surgery. The drug has been formulated in poly (lactic/glycolic) acid (PLGA) nanoparticles (PF-F1NPs with cPF 1.5mg/mL, PF-F2NPs with cPF 1mg/mL) produced by solvent displacement technique and tested the in vitro cytotoxicity, ex vivo corneal permeation, in vivo ocular tolerance and in vivo anti-inflammatory efficacy of PF-F1NPs, PF-F2NPs, in comparison to eye drops conventional dosage form (Oftalar(®), PF 1mg/mL) and free drug solution (PF dissolved in PBS, 1.5mg/mL). The mean particle size of both formulations was around 350nm, with polydispersity index below 0.1, and a net negative charge of -7.41mV and -8.5mV for PF-F1NPs and PF-F2NPs, respectively. Y-79 human retinoblastoma cell line was used to evaluate the cytotoxicity of PF-F1NPs and PF-F2NPs, which were compared to blank NPs and free drug solution (PF dissolved in PBS, 1.5mg/mL). Concentrations up to 75μg/mL exhibited no toxicity to Y-79 cells, whereas at 150μg/mL a decrease of about 80% on the cell viability was observed after exposing the cells to PF-F1NPs. When treating the Y-79 cells with concentrations of PF-F2NPs between 1μg/mL to 100μg/mL, the cell viability was similar to control values after 24h and 48h of exposure. An ex vivo corneal permeation study was carried out in New Zealand rabbits. A very similar profile has been observed for the permeation of PF through the cornea when administered as eye drops and as free drug solution, which was kept much lower in comparison to PF-NPs formulations. The permeated amount of PF from the PF-F1NPs was slightly smaller than from PF-F2NPs, attributed to the increase of viscosity of the formulations with the increase of cPVA concentration. New Zealand white rabbits were also used to evaluate the irritancy of PF-F1NPs and PF-F2NPs, which demonstrated to be well-tolerated to the eye (i.e. the mean total score (MTS) was 0). PF-F2NPs exhibited the highest QP (amounts of PF permeated in the cornea) and significantly reduced the ocular edema compared to the tested formulations. The QR (amounts of PF retained in the cornea) of the PF-F1NPs was greater than that obtained for PF-F2NPs. Copyright © 2016 Elsevier B.V. All rights reserved.

Magnetic field controlled floating-zone single crystal growth of intermetallic compounds

NASA Astrophysics Data System (ADS)

Hermann, R.; Gerbeth, G.; Priede, J.

2013-03-01

Radio-frequency (RF) floating zone single crystal growth is an important technique for the preparation of single bulk crystals. The advantage of the floating-zone method is the crucible-free growth of single crystals of reactive materials with high melting points. The strong heat diffusion on the surface, as well as the melt convection in the molten zone due to induction heating, often leads to an undesired solid-liquid interface geometry with a concave (towards the solid phase) outer rim. These concave parts aggravate the single crystal growth over the full cross-section. A two-phase stirrer was developed at IFW Dresden in order to avoid the problems connected with these concave parts. It acts as a magnetic field pump and changes the typical double vortex structure to a single roll structure, thus pushing hot melt into the regions where the concave parts may arise. The current in the secondary coil is induced by the primary coil, and the capacitor and the resistance of the secondary circuit are adjusted to get a stable 90 degree phase-shift between the coil currents. Single crystal growth of industrial relevant RuAl and TiAl intermetallic compounds was performed based on the material parameters and using the adjusted two-phase stirrer. Very recently, the magnetic system was applied to the crystal growth of biocompatible TiNb alloys and antiferromagnetic Heusler MnSi compounds.

Improved Readout Scheme for SQUID-Based Thermometry

NASA Technical Reports Server (NTRS)

Penanen, Konstantin

2007-01-01

An improved readout scheme has been proposed for high-resolution thermometers, (HRTs) based on the use of superconducting quantum interference devices (SQUIDs) to measure temperature- dependent magnetic susceptibilities. The proposed scheme would eliminate counting ambiguities that arise in the conventional scheme, while maintaining the superior magnetic-flux sensitivity of the conventional scheme. The proposed scheme is expected to be especially beneficial for HRT-based temperature control of multiplexed SQUIDbased bolometer sensor arrays. SQUID-based HRTs have become standard for measuring and controlling temperatures in the sub-nano-Kelvin temperature range in a broad range of low-temperature scientific and engineering applications. A typical SQUIDbased HRT that utilizes the conventional scheme includes a coil wound on a core made of a material that has temperature- dependent magnetic susceptibility in the temperature range of interest. The core and the coil are placed in a DC magnetic field provided either by a permanent magnet or as magnetic flux inside a superconducting outer wall. The aforementioned coil is connected to an input coil of a SQUID. Changes in temperature lead to changes in the susceptibility of the core and to changes in the magnetic flux detected by the SQUID. The SQUID readout instrumentation is capable of measuring magnetic-flux changes that correspond to temperature changes down to a noise limit .0.1 nK/Hz1/2. When the flux exceeds a few fundamental flux units, which typically corresponds to a temperature of .100 nK, the SQUID is reset. The temperature range can be greatly expanded if the reset events are carefully tracked and counted, either by a computer running appropriate software or by a dedicated piece of hardware.

Moment free toroidal magnet

DOEpatents

Bonanos, Peter

1983-01-01

A toroidal magnet for confining a high magnetic field for use in fusion reactor research and nuclear particle detection. The magnet includes a series of conductor elements arranged about and fixed at its small major radius portion to the outer surface of a central cylindrical support each conductor element having a geometry such as to maintain the conductor elements in pure tension when a high current flows therein, and a support assembly which redistributes all or part of the tension which would otherwise arise in the small major radius portion of each coil element to the large major radius portion thereof.

Plasmodium falciparum Hop (PfHop) Interacts with the Hsp70 Chaperone in a Nucleotide-Dependent Fashion and Exhibits Ligand Selectivity.

PubMed

Zininga, Tawanda; Makumire, Stanely; Gitau, Grace Wairimu; Njunge, James M; Pooe, Ofentse Jacob; Klimek, Hanna; Scheurr, Robina; Raifer, Hartmann; Prinsloo, Earl; Przyborski, Jude M; Hoppe, Heinrich; Shonhai, Addmore

2015-01-01

Heat shock proteins (Hsps) play an important role in the development and pathogenicity of malaria parasites. One of the most prominent functions of Hsps is to facilitate the folding of other proteins. Hsps are thought to play a crucial role when malaria parasites invade their host cells and during their subsequent development in hepatocytes and red blood cells. It is thought that Hsps maintain proteostasis under the unfavourable conditions that malaria parasites encounter in the host environment. Although heat shock protein 70 (Hsp70) is capable of independent folding of some proteins, its functional cooperation with heat shock protein 90 (Hsp90) facilitates folding of some proteins such as kinases and steroid hormone receptors into their fully functional forms. The cooperation of Hsp70 and Hsp90 occurs through an adaptor protein called Hsp70-Hsp90 organising protein (Hop). We previously characterised the Hop protein from Plasmodium falciparum (PfHop). We observed that the protein co-localised with the cytosol-localised chaperones, PfHsp70-1 and PfHsp90 at the blood stages of the malaria parasite. In the current study, we demonstrated that PfHop is a stress-inducible protein. We further explored the direct interaction between PfHop and PfHsp70-1 using far Western and surface plasmon resonance (SPR) analyses. The interaction of the two proteins was further validated by co-immunoprecipitation studies. We observed that PfHop and PfHsp70-1 associate in the absence and presence of either ATP or ADP. However, ADP appears to promote the association of the two proteins better than ATP. In addition, we investigated the specific interaction between PfHop TPR subdomains and PfHsp70-1/ PfHsp90, using a split-GFP approach. This method allowed us to observe that TPR1 and TPR2B subdomains of PfHop bind preferentially to the C-terminus of PfHsp70-1 compared to PfHsp90. Conversely, the TPR2A motif preferentially interacted with the C-terminus of PfHsp90. Finally, we observed that recombinant PfHop occasionally eluted as a protein species of twice its predicted size, suggesting that it may occur as a dimer. We conducted SPR analysis which suggested that PfHop is capable of self-association in presence or absence of ATP/ADP. Overall, our findings suggest that PfHop is a stress-inducible protein that directly associates with PfHsp70-1 and PfHsp90. In addition, the protein is capable of self-association. The findings suggest that PfHop serves as a module that brings these two prominent chaperones (PfHsp70-1 and PfHsp90) into a functional complex. Since PfHsp70-1 and PfHsp90 are essential for parasite growth, findings from this study are important towards the development of possible antimalarial inhibitors targeting the cooperation of these two chaperones.

Population genetic structure and natural selection of Plasmodium falciparum apical membrane antigen-1 in Myanmar isolates.

PubMed

Kang, Jung-Mi; Lee, Jinyoung; Moe, Mya; Jun, Hojong; Lê, Hương Giang; Kim, Tae Im; Thái, Thị Lam; Sohn, Woon-Mok; Myint, Moe Kyaw; Lin, Khin; Shin, Ho-Joon; Kim, Tong-Soo; Na, Byoung-Kuk

2018-02-07

Plasmodium falciparum apical membrane antigen-1 (PfAMA-1) is one of leading blood stage malaria vaccine candidates. However, genetic variation and antigenic diversity identified in global PfAMA-1 are major hurdles in the development of an effective vaccine based on this antigen. In this study, genetic structure and the effect of natural selection of PfAMA-1 among Myanmar P. falciparum isolates were analysed. Blood samples were collected from 58 Myanmar patients with falciparum malaria. Full-length PfAMA-1 gene was amplified by polymerase chain reaction and cloned into a TA cloning vector. PfAMA-1 sequence of each isolate was sequenced. Polymorphic characteristics and effect of natural selection were analysed with using DNASTAR, MEGA4, and DnaSP programs. Polymorphic nature and natural selection in 459 global PfAMA-1 were also analysed. Thirty-seven different haplotypes of PfAMA-1 were identified in 58 Myanmar P. falciparum isolates. Most amino acid changes identified in Myanmar PfAMA-1 were found in domains I and III. Overall patterns of amino acid changes in Myanmar PfAMA-1 were similar to those in global PfAMA-1. However, frequencies of amino acid changes differed by country. Novel amino acid changes in Myanmar PfAMA-1 were also identified. Evidences for natural selection and recombination event were observed in global PfAMA-1. Among 51 commonly identified amino acid changes in global PfAMA-1 sequences, 43 were found in predicted RBC-binding sites, B-cell epitopes, or IUR regions. Myanmar PfAMA-1 showed similar patterns of nucleotide diversity and amino acid polymorphisms compared to those of global PfAMA-1. Balancing natural selection and intragenic recombination across PfAMA-1 are likely to play major roles in generating genetic diversity in global PfAMA-1. Most common amino acid changes in global PfAMA-1 were located in predicted B-cell epitopes where high levels of nucleotide diversity and balancing natural selection were found. These results highlight the strong selective pressure of host immunity on the PfAMA-1 gene. These results have significant implications in understanding the nature of Myanmar PfAMA-1 along with global PfAMA-1. They also provide useful information for the development of effective malaria vaccine based on this antigen.

A Chimeric Plasmodium falciparum Merozoite Surface Protein Vaccine Induces High Titers of Parasite Growth Inhibitory Antibodies

PubMed Central

Alaro, James R.; Partridge, Andrea; Miura, Kazutoyo; Diouf, Ababacar; Lopez, Ana M.; Angov, Evelina; Long, Carole A.

2013-01-01

The C-terminal 19-kDa domain of Plasmodium falciparum merozoite surface protein 1 (PfMSP119) is an established target of protective antibodies. However, clinical trials of PfMSP142, a leading blood-stage vaccine candidate which contains the protective epitopes of PfMSP119, revealed suboptimal immunogenicity and efficacy. Based on proof-of-concept studies in the Plasmodium yoelii murine model, we produced a chimeric vaccine antigen containing recombinant PfMSP119 (rPfMSP119) fused to the N terminus of P. falciparum merozoite surface protein 8 that lacked its low-complexity Asn/Asp-rich domain, rPfMSP8 (ΔAsn/Asp). Immunization of mice with the chimeric rPfMSP1/8 vaccine elicited strong T cell responses to conserved epitopes associated with the rPfMSP8 (ΔAsn/Asp) fusion partner. While specific for PfMSP8, this T cell response was adequate to provide help for the production of high titers of antibodies to both PfMSP119 and rPfMSP8 (ΔAsn/Asp) components. This occurred with formulations adjuvanted with either Quil A or with Montanide ISA 720 plus CpG oligodeoxynucleotide (ODN) and was observed in both inbred and outbred strains of mice. PfMSP1/8-induced antibodies were highly reactive with two major alleles of PfMSP119 (FVO and 3D7). Of particular interest, immunization with PfMSP1/8 elicited higher titers of PfMSP119-specific antibodies than a combined formulation of rPfMSP142 and rPfMSP8 (ΔAsn/Asp). As a measure of functionality, PfMSP1/8-specific rabbit IgG was shown to potently inhibit the in vitro growth of blood-stage parasites of the FVO and 3D7 strains of P. falciparum. These data support the further testing and evaluation of this chimeric PfMSP1/8 antigen as a component of a multivalent vaccine for P. falciparum malaria. PMID:23897613

Interaction of apicoplast-encoded elongation factor (EF) EF-Tu with nuclear-encoded EF-Ts mediates translation in the Plasmodiumfalciparum plastid.

PubMed

Biswas, Subir; Lim, Erin E; Gupta, Ankit; Saqib, Uzma; Mir, Snober S; Siddiqi, Mohammad Imran; Ralph, Stuart A; Habib, Saman

2011-03-01

Protein translation in the plastid (apicoplast) of Plasmodium spp. is of immense interest as a target for potential anti-malarial drugs. However, the molecular data on apicoplast translation needed for optimisation and development of novel inhibitors is lacking. We report characterisation of two key translation elongation factors in Plasmodium falciparum, apicoplast-encoded elongation factor PfEF-Tu and nuclear-encoded PfEF-Ts. Recombinant PfEF-Tu hydrolysed GTP and interacted with its presumed nuclear-encoded partner PfEF-Ts. The EF-Tu inhibitor kirromycin affected PfEF-Tu activity in vitro, indicating that apicoplast EF-Tu is indeed the target of this drug. The predicted PfEF-Ts leader sequence targeted GFP to the apicoplast, confirming that PfEF-Ts functions in this organelle. Recombinant PfEF-Ts mediated nucleotide exchange on PfEF-Tu and homology modeling of the PfEF-Tu:PfEF-Ts complex revealed PfEF-Ts-induced structural alterations that would expedite GDP release from PfEF-Tu. Our results establish functional interaction between two apicoplast translation factors encoded by genes residing in different cellular compartments and highlight the significance of their sequence/structural differences from bacterial elongation factors in relation to inhibitor activity. These data provide an experimental system to study the effects of novel inhibitors targeting PfEF-Tu and PfEF-Tu.PfEF-Ts interaction. Our finding that apicoplast EF-Tu possesses chaperone-related disulphide reductase activity also provides a rationale for retention of the tufA gene on the plastid genome. Copyright © 2010 Australian Society for Parasitology Inc. All rights reserved.

Seeking and sharing: why the pulmonary fibrosis community engages the web 2.0 environment.

PubMed

Albright, Karen; Walker, Tarik; Baird, Susan; Eres, Linda; Farnsworth, Tara; Fier, Kaitlin; Kervitsky, Dolly; Korn, Marjorie; Lederer, David J; McCormick, Mark; Steiner, John F; Vierzba, Thomas; Wamboldt, Frederick S; Swigris, Jeffrey J

2016-01-12

Pulmonary fibrosis (PF) is a rare, progressive disease that affects patients and their loved ones on many levels. We sought to better understand the needs and interests of PF patients and their loved ones (collectively "reader-participants") by systematically analyzing their engagement with the World Wide Web (the current version referred to as Web 2.0). Data were collected from three PF-focused, interactive websites hosted by physician-investigators with expertise in PF. All data generated by reader-participants for approximately 10 months were downloaded and then analyzed using qualitative content analysis methods. PF experts posted 38 blog entries and reader-participants posted 40 forum entries. Blogs received 363 responses, and forum entries received 108 responses from reader-participants. Reader-participants primarily used the three websites to seek information from or offer a contribution to the PF community. Information was sought about PF symptoms, diagnosis, prognosis, treatments, research, pathophysiology, and disease origin; reader-participants also made requests for new posts and pleas for research and sought clarification on existing content. Contributions included personal narratives about experiences with PF, descriptions of activities or behaviors found to be helpful with PF symptoms, resources or information about PF, and supportive comments to other PF sufferers. PF patients and their loved ones engage the Web 2.0 environment at these PF-focused sites to satisfy their needs to better understand PF and its impacts and to support others facing similar challenges. Clinicians may find it beneficial to encourage PF patients' involvement in internet forums that foster dynamic, bi-directional information sharing.

Democratization as a United States Strategy for Middle East Security

DTIC Science & Technology

2005-03-18

the Middle East presents a wide variety of governments across the region. Republics exists in Algeria, Egypt, Lebanon , Syria, Tunisia, and Yemen...PF 4 5 PF 4 5 PF 4 5 PF 4 5 PF Lebanon 6 5 NF 6 5 NF 6 5 NF 6 5 NF 6 5 NF Libya 7 7 NF 7 7 NF 7 7 NF 7 7 NF 7 7 NF Morocco 5 4 PF 5 5 PF 5 5 PF 5 5...more open discussion of previously taboo topics.17 Syria’s firm control continues to be the greatest impediment to freedom in Lebanon . The Lebanese

Fabrication and test of model superconducting inflector for g-2 at FNAL

DOE PAGES

Krave, Steven; Kashikhin, Vladimir S.; Strauss, Thomas

2017-03-01

The new FNAL g-2 experiment is based on the muon storage ring previously used at BNL. The 1.45 T dipole magnetic field in the storage ring is required to have very high (1 ppm) homogeneity. The muon beam injected into the ring must be transported through the magnet yoke and the main superconducting coil cryostat with minimal distortions. The old inflector magnet shielded the main dipole fringe field inside the muon transport beam pipe, with an outer NbTi superconducting screen, and did not disturb the field in the area of circulating beam. Nevertheless, this magnet had coils with closed endsmore » in which a large fraction of muon beam particles were lost. A new magnet is envisioned utilizing the same cross section as the original with open ends for improved beam transport. A model magnet has been wound utilizing 3d printed parts to verify the magnetic behavior of the magnet at room temperature and validate winding of the complicated geometry required for the magnet ends. Finally, room temperature magnetic measurements have been performed and confirm the magnetic design« less

Laminar composite structures for high power actuators

NASA Astrophysics Data System (ADS)

Hobosyan, M. A.; Martinez, P. M.; Zakhidov, A. A.; Haines, C. S.; Baughman, R. H.; Martirosyan, K. S.

2017-05-01

Twisted laminar composite structures for high power and large-stroke actuators based on coiled Multi Wall Carbon Nanotube (MWNT) composite yarns were crafted by integrating high-density Nanoenergetic Gas Generators (NGGs) into carbon nanotube sheets. The linear actuation force, resulting from the pneumatic force caused by expanding gases confined within the pores of laminar structures and twisted carbon nanotube yarns, can be further amplified by increasing NGG loading and yarns twist density, as well as selecting NGG compositions with high energy density and large-volume gas generation. Moreover, the actuation force and power can be tuned by the surrounding environment, such as to increase the actuation by combustion in ambient air. A single 300-μm-diameter integrated MWNT/NGG coiled yarn produced 0.7 MPa stress and a contractile specific work power of up to 4.7 kW/kg, while combustion front propagated along the yarn at a velocity up to 10 m/s. Such powerful yarn actuators can also be operated in a vacuum, enabling their potential use for deploying heavy loads in outer space, such as to unfold solar panels and solar sails.

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

Comparative analysis of linear motor geometries for Stirling coolers

NASA Astrophysics Data System (ADS)

R, Rajesh V.; Kuzhiveli, Biju T.

2017-12-01

Compared to rotary motor driven Stirling coolers, linear motor coolers are characterized by small volume and long life, making them more suitable for space and military applications. The motor design and operational characteristics have a direct effect on the operation of the cooler. In this perspective, ample scope exists in understanding the behavioural description of linear motor systems. In the present work, the authors compare and analyze different moving magnet linear motor geometries to finalize the most favourable one for Stirling coolers. The required axial force in the linear motors is generated by the interaction of magnetic fields of a current carrying coil and that of a permanent magnet. The compact size, commercial availability of permanent magnets and low weight requirement of the system are quite a few constraints for the design. The finite element analysis performed using Maxwell software serves as the basic tool to analyze the magnet movement, flux distribution in the air gap and the magnetic saturation levels on the core. A number of material combinations are investigated for core before finalizing the design. The effect of varying the core geometry on the flux produced in the air gap is also analyzed. The electromagnetic analysis of the motor indicates that the permanent magnet height ought to be taken in such a way that it is under the influence of electromagnetic field of current carrying coil as well as the outer core in the balanced position. This is necessary so that sufficient amount of thrust force is developed by efficient utilisation of the air gap flux density. Also, the outer core ends need to be designed to facilitate enough room for the magnet movement under the operating conditions.

Risk factors and outcomes of postoperative pancreatic fistula after pancreatico-duodenectomy: an audit of 532 consecutive cases.

PubMed

Fu, Shun-Jun; Shen, Shun-Li; Li, Shao-Qiang; Hu, Wen-Jie; Hua, Yun-Peng; Kuang, Ming; Liang, Li-Jian; Peng, Bao-Gang

2015-03-26

Pancreatic fistula (PF) remains the most challenging complication after pancreaticoduodenectomy (PD). The purpose of this study was to identify the risk factors of PF and delineate its impact on patient outcomes. We retrospectively reviewed clinical data of 532 patients who underwent PD and divided them into PF group and no PF group. Risk factors and outcomes of PF following PD were examined. PF was found in 65 (12.2%) cases, of whom 11 were classified into ISGPF grade A, 42 grade B, and 12 grade C. Clinically serious postoperative complications in the PF versus no PF group were mortality, abdominal bleeding, bile leak, intra-abdominal abscess and pneumonia. Univariate and multivariate analysis showed that blood loss ≥ 500 ml, pancreatic duct diameter ≤ 3 mm and pancreaticojejunostomy type were independent risk factors of PF after PD. Blood loss ≥ 500 ml, pancreatic duct diameter ≤ 3 mm and pancreatico-jejunostomy type were independent risk factors of PF after PD. PF was related with higher mortality rate, longer hospital stay, and other complications.

Enhanced Oral Bioavailability of Pueraria Flavones by a Novel Solid Self-microemulsifying Drug Delivery System (SMEDDS) Dropping Pills.

PubMed

Guan, Qingxiang; Zhang, Guangyuan; Sun, Shilin; Fan, Hongbo; Sun, Cheng; Zhang, Shaoyuan

2016-05-01

To improve bioavailability of pueraria flavones (PF), a self-microemulsifying drug delivery system (SMEDDS) dropping pills composed of PF, Crodamol GTCC, Maisine 35-1, Cremophor RH 40, 1,2-propylene glycol and polyethylene glycol 6000 (PEG6000) was developed. Particle size, zeta potential, morphology and in vitro drug release were investigated, respectively. Pharmacokinetics, bioavailability of PF-SMEDDS dropping pills and commercial Yufengningxin dropping pills were also evaluated and compared in rats. Puerarin treated as the representative component of PF was analyzed. Dynamic light scattering showed the ability of PF-SMEDDS dropping pills to form a nanoemulsion droplet size in aqueous media. The type of media showed no significant effects on the release rate of PF. PF-SMEDDS dropping pills were able to improve the in vitro release rate of PF, and the in vitro release of these dropping pills was significantly faster than that of Yufengningxin dropping pills. There was a dramatic difference between the mean value of t1/2, peak concentration (Cmax), the area of concentration-time curve from 0 to 6 h (AUC0-6 h) of PF-SMEDDS dropping pills and that of commercial Yufengningxin dropping pills. A pharmacokinetic study showed that the bioavailability of PF was greatly enhanced by PF-SMEDDS dropping pills. The value of Cmax and relative bioavailability of PF-SMEDDS dropping pills were dramatically improved by an average of 1.69- and 2.36-fold compared with that of Yufengningxin dropping pills after gavage administration, respectively. It was concluded that bioavailability of PF was greatly improved and that PF-SMEDDS dropping pills might be an encouraging strategy to enhance the oral bioavailability of PF.

Development of a micro nuclear magnetic resonance system

NASA Astrophysics Data System (ADS)

Goloshevsky, Artem

Application of Nuclear Magnetic Resonance (NMR) to on-line/in-line control of industrial processes is currently limited by equipment costs and requirements for installation. A superconducting magnet generating strong fields is the most expensive part of a typical NMR instrument. In industrial environments, fringe magnetic fields make accommodation of NMR instruments difficult. However, a portable, low-cost and low-field magnetic resonance system can be used in virtually any environment. Development of a number of hardware components for a portable, low-cost NMR instrument is reported in this dissertation. Chapter one provides a discussion on a miniaturized Helmholtz spiral radio-frequency (RF) coil (average diameter equal to 3.5 mm) and an NMR probe built around a capillary (outer diameter = 1.59 mm and inner diameter = 1.02 mm) for flow imaging. Experiments of NMR spectroscopy, static and dynamic (flow) imaging, conducted with the use of the miniaturized coil, are described. Chapter two presents a microfabricated package of two biaxial gradient coils and a Helmholtz RF coil. Planar configuration of discrete wires was used to create magnetic field gradients. Performance of the microfabricated gradient coils while imaging water flow compared well with a commercial gradient set of much larger size. Chapter three reports on flow imaging experiments with power law fluids (aqueous solutions of sodium salt of carboxymethyl cellulose (CMC)) of different viscosities, carried out in the NMR probe with the miniaturized RF coil and capillary. Viscosities of the CMC solutions were determined based on the curve fits of the velocity profiles and simultaneous measurements of the flow rates. The curve fits were carried out according to the power law model equations. The NMR viscosity measurements compared well with measurements of the same CMC samples, performed on a conventional rotational rheometer. A portable, home-built transceiver, designed for NMR applications utilizing a miniaturized RF coil, is described in chapter four. The maximum RF power, occurring in the transceiver, was 21.5 dBm. Two transistor-transistor logic (TTL) switches functioned as an active duplexer. A quadrature detection scheme was used. The transceiver, combined with a filter/amplifier module, data acquisition (DAQ and RF generating PC boards, was successfully tested in NMR spectroscopy experiments at low magnetic field. It was demonstrated that, starting with the RF probe, a typical, large size NMR instrument can be miniaturized without impairment to the quality of the data. Such an instrument will be readily used in many industrial process control applications (e.g. for analysis of material properties and identification of chemicals).

High mobility group box (HMGB) proteins of Plasmodium falciparum: DNA binding proteins with pro-inflammatory activity.

PubMed

Kumar, Krishan; Singal, Ankita; Rizvi, M Moshahid A; Chauhan, Virander S

2008-06-01

High mobility group box chromosomal protein 1 (HMGB1), known as an abundant, non-histone architectural chromosomal protein, is highly conserved across different species. Homologues of HMGB1 were identified and cloned from malaria parasite, Plasmodium falciparum. Sequence analyses showed that the P. falciparum HMGB1 (PfHMGB1) exhibits 45, 23 and 18%, while PfHMGB2 shares 42, 21 and 17% homology with Saccharomyces cerevisiae, human and mouse HMG box proteins respectively. Parasite PfHMGB1and PfHMGB2 proteins contain one HMG Box domain similar to B-Box of mammalian HMGB1. Electrophoretic Mobility Shift Assay (EMSA) showed that recombinant PfHMGB1 and PfHMGB2 bind to DNA. Immunofluorescence Assay using specific antibodies revealed that these proteins are expressed abundantly in the ring stage nuclei. Significant levels of PfHMGB1 and PfHMGB2 were also present in the parasite cytosol at trophozoite and schizont stages. Both, PfHMGB1 and PfHMGB2 were found to be potent inducers of pro-inflammatory cytokines such as TNFalpha from mouse peritoneal macrophages as analyzed by both reverse transcription PCR and by ELISA. These results suggest that secreted PfHMGB1 and PfHMGB2 may be responsible for eliciting/ triggering host inflammatory immune responses associated with malaria infection.

Sterile protection against human malaria by chemoattenuated PfSPZ vaccine.

PubMed

Mordmüller, Benjamin; Surat, Güzin; Lagler, Heimo; Chakravarty, Sumana; Ishizuka, Andrew S; Lalremruata, Albert; Gmeiner, Markus; Campo, Joseph J; Esen, Meral; Ruben, Adam J; Held, Jana; Calle, Carlos Lamsfus; Mengue, Juliana B; Gebru, Tamirat; Ibáñez, Javier; Sulyok, Mihály; James, Eric R; Billingsley, Peter F; Natasha, K C; Manoj, Anita; Murshedkar, Tooba; Gunasekera, Anusha; Eappen, Abraham G; Li, Tao; Stafford, Richard E; Li, Minglin; Felgner, Phil L; Seder, Robert A; Richie, Thomas L; Sim, B Kim Lee; Hoffman, Stephen L; Kremsner, Peter G

2017-02-23

A highly protective malaria vaccine would greatly facilitate the prevention and elimination of malaria and containment of drug-resistant parasites. A high level (more than 90%) of protection against malaria in humans has previously been achieved only by immunization with radiation-attenuated Plasmodium falciparum (Pf) sporozoites (PfSPZ) inoculated by mosquitoes; by intravenous injection of aseptic, purified, radiation-attenuated, cryopreserved PfSPZ ('PfSPZ Vaccine'); or by infectious PfSPZ inoculated by mosquitoes to volunteers taking chloroquine or mefloquine (chemoprophylaxis with sporozoites). We assessed immunization by direct venous inoculation of aseptic, purified, cryopreserved, non-irradiated PfSPZ ('PfSPZ Challenge') to malaria-naive, healthy adult volunteers taking chloroquine for antimalarial chemoprophylaxis (vaccine approach denoted as PfSPZ-CVac). Three doses of 5.12 × 10 4 PfSPZ of PfSPZ Challenge at 28-day intervals were well tolerated and safe, and prevented infection in 9 out of 9 (100%) volunteers who underwent controlled human malaria infection ten weeks after the last dose (group III). Protective efficacy was dependent on dose and regimen. Immunization with 3.2 × 10 3 (group I) or 1.28 × 10 4 (group II) PfSPZ protected 3 out of 9 (33%) or 6 out of 9 (67%) volunteers, respectively. Three doses of 5.12 × 10 4 PfSPZ at five-day intervals protected 5 out of 8 (63%) volunteers. The frequency of Pf-specific polyfunctional CD4 memory T cells was associated with protection. On a 7,455 peptide Pf proteome array, immune sera from at least 5 out of 9 group III vaccinees recognized each of 22 proteins. PfSPZ-CVac is a highly efficacious vaccine candidate; when we are able to optimize the immunization regimen (dose, interval between doses, and drug partner), this vaccine could be used for combination mass drug administration and a mass vaccination program approach to eliminate malaria from geographically defined areas.

Effects of 17β-estradiol on the release of monocyte chemotactic protein-1 and MAPK activity in monocytes stimulated with peritoneal fluid from endometriosis patients.

PubMed

Lee, Dong-Hyung; Kim, Seung-Chul; Joo, Jong-Kil; Kim, Hwi-Gon; Na, Young-Jin; Kwak, Jong-Young; Lee, Kyu-Sup

2012-03-01

Hormones and inflammation have been implicated in the pathological process of endometriosis; therefore, we investigated the combined effects of 17β-estradiol (E2) and peritoneal fluid obtained from patients with endometriosis (ePF) or a control peritoneal fluid (cPF) obtained from patients without endometriosis on the release of monocyte chemotactic protein-1 (MCP-1) by monocytes and the role of signaling pathways. Monocytes were cultured with ePF and cPF in the presence of E2; the MCP-1 levels in the supernatants were then measured by ELISA. In addition, mitogen activated protein kinase (MAPK) activation was measured by Western blotting of phosphorylated proteins. E2 down-regulated MCP-1 release by lipopolysaccharide- or cPF-treated monocytes, but failed to suppress its release by ePF-treated monocytes. The release of MCP-1 by ePF- and cPF-treated monocytes was efficiently abrogated by p38 mitogen activated protein kinase (MAPK) inhibitors; however, the MCP-1 release by cPF-treated monocytes, but not by ePF-treated monocytes, was blocked by a MAPK kinase inhibitor. In addition, ePF and cPF induced the phosphorylation of extracellular stress regulated kinase (ERK)1/2, p38 MAPK and c-Jun N-terminal kinase (JNK). E2 decreased the phosphorylation of p38 MAPK, but not ERK1/2 in ePF-treated monocytes; however, E2 decreased the phosphorylation of p38 MAPK, ERK1/2 and JNK in cPF-treated monocytes. The ability of E2 to modulate MCP-1 production is impaired in ePF-treated monocytes, which may be related to regulation of MAPK activity. These findings suggest that the failure of E2 to suppress ePF-treated production of MCP-1 may be involved in the pathogenesis of endometriosis. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

The Pavlovian power of palatable food: lessons for weight-loss adherence from a new rodent model of cue-induced overeating

PubMed Central

Boggiano, M M; Dorsey, J R; Thomas, J M; Murdaugh, D L

2009-01-01

Objective Relapsing to overeating is a stubborn problem in obesity treatment. We tested the hypothesis that context cues surrounding palatable food (PF) intake have the power to disrupt caloric regulation even of less PF. Context cues are non-food cues that are in the environment where PF is habitually eaten. Design Rats were conditioned to associate intake of Oreo cookies as the PF to cages with distinct context cues that differed from cues in cages were they were only given chow. PF naturally stimulated greater caloric intake. The rats were then tested in the PF cage with only chow available to determine if the PF-paired cues, alone, could elicit overeating of plain chow. Subjects Non food-deprived female Sprague-Dawley rats. Measurements Intake of plain chow under PF-paired cues vs. chow-paired cues was compared. This was also measured in tests that included a morsel of PF as a priming stimulus. We also controlled for any effect of binge-prone vs. binge–resistant status to predict cued-overeating. Results Rats consumed significantly more chow when exposed to context cues previously paired with PF than with chow (p<0.01). This effect occurred using various cues (e.g., different types of bedding or wallpaper). The effect was strengthened by priming with a morsel of PF (p<0.001) and was unaffected by baseline differences in propensity to binge on PF. Conclusion Context-cues associated with PF intake can drive overeating even of a less PF and abolish the ability of rats to compensate for the calories of a PF primer. Just as drug-associated context cues can reinstate drug-addiction relapse, PF-paired cues may trigger overeating relapses linked to weight regain and obesity. This model should help identify the reflex-like biology that sabotages attempts to adhere to healthy reduced calorie regimens and call greater attention to the cue-factor in the treatment of binge-eating and obesity. PMID:19350040

Physalis floridana Cell Number Regulator1 encodes a cell membrane-anchored modulator of cell cycle and negatively controls fruit size

PubMed Central

Li, Zhichao; He, Chaoying

2015-01-01

Physalis species show a significant variation in berry size; however, the underlying molecular basis is unknown. In this work, we showed that cell division difference in the ovaries might contribute to the ultimate berry size variation within Physalis species, and that mRNA abundance of Physalis floridana Cell Number Regulator1 (PfCNR1), the putative orthologue of the tomato fruit weight 2.2 (FW2.2), was negatively correlated with cell division in the ovaries. Moreover, heterochronic expression variation of the PfCNR1 genes in the ovaries concomitantly correlated with berry weight variation within Physalis species. In transgenic Physalis, multiple organ sizes could be negatively controlled by altering PfCNR1 levels, and cell division instead of cell expansion was primarily affected. PfCNR1 was shown to be anchored in the plasma membrane and to interact with PfAG2 (an AGAMOUS-like protein determining ovary identity). The expression of PfCYCD2;1, a putative orthologue of the mitosis-specific gene CyclinD2;1 in the cell cycle was negatively correlated with the PfCNR1 mRNA levels. PfAG2 was found to selectively bind to the CArG-box in the PfCYCD2;1 promoter and to repress PfCYCD2;1 expression, thus suggesting a PfAG2-mediated pathway for PfCNR1 to regulate cell division. The interaction of PfCNR1 with PfAG2 enhanced the repression of PfCYCD2;1 expression. The nuclear import of PfAG2 was essential in the proposed pathway. Our data provide new insights into the developmental pathways of a cell membrane-anchored protein that modulates cell division and governs organ size determination. This study also sheds light on the link between organ identity and organ growth in plants. PMID:25305759

Baking loss of bread with special emphasis on increasing water holding capacity.

PubMed

Kotoki, D; Deka, S C

2010-01-01

Potato flour (PF), hydroxypropyl methylcellulose (HPMC) and honey were used as baking agents and their effects on baking loss and sensory quality were studied. PF at 1, 2 and 4% levels decreased baking loss followed by HPMC and honey. Water absorption was substantially high with the HPMC (70.8-80.8%) and PF (61.7-71.7%) compared to honey and normal standard bread. PF incorporation increased shelf-life (6-7 days) as compared to HPMC and honey. HPMC incorporated bread had higher moisture content (36.8-38.0%) followed by PF (34.5-35.8%) and honey (34.7%). The ash content was in the order of PF (1%) > honey (4%) > PF (2%) > normal bread > HPMC (0.5 g) > PF (4%) > HPMC (1 g) > HPMC (1.5 g). PF incorporated bread had sensorily highest acceptance followed by HPMC and honey.

Unpacking personalized feedback: an exploratory study of the impact of its components and the reactions it elicits among problem drinking men who have sex with men.

PubMed

Kuerbis, Alexis Noel; Schaumberg, Katherine; Davis, Christine M; Hail, Lisa; Morgenstern, Jon

2014-03-01

Personalized feedback (PF) has demonstrated effectiveness in reducing drinking. Few studies have examined its effectiveness with adult problem drinkers or its potential mediators or moderators, including developing discrepancy. This study aimed to identify potential mediators and moderators of PF provided to adult problem drinking men who have sex with men (PDMSM). An exploratory analysis of PF provided to PDMSM in the context of modified behavioral self-control therapy (N = 90). The association of individual items of PF, severity of PF, and independently rated, in-session participant reactions to PF with drinking outcomes (mean drinks per drinking day, MDDD) were examined using correlations and logistic and linear regression. Significant pre-post differences in MDDD emerged. Other drug risk, family risk, and having an abnormal liver enzyme test result were significantly associated with proxies for developed discrepancy in expected directions; however, no PF item or reaction to PF predicted drinking outcomes. Severity of PF was not associated with participant reactions or drinking outcome. PF may be an effective intervention for PDMSM. Further research is needed to identify potential mediators and moderators of PF among adults.

Multiple Drugs Compete for Transport via the Plasmodium falciparum Chloroquine Resistance Transporter at Distinct but Interdependent Sites*

PubMed Central

Bellanca, Sebastiano; Summers, Robert L.; Meyrath, Max; Dave, Anurag; Nash, Megan N.; Dittmer, Martin; Sanchez, Cecilia P.; Stein, Wilfred D.; Martin, Rowena E.; Lanzer, Michael

2014-01-01

Mutations in the “chloroquine resistance transporter” (PfCRT) are a major determinant of drug resistance in the malaria parasite Plasmodium falciparum. We have previously shown that mutant PfCRT transports the antimalarial drug chloroquine away from its target, whereas the wild-type form of PfCRT does not. However, little is understood about the transport of other drugs via PfCRT or the mechanism by which PfCRT recognizes different substrates. Here we show that mutant PfCRT also transports quinine, quinidine, and verapamil, indicating that the protein behaves as a multidrug resistance carrier. Detailed kinetic analyses revealed that chloroquine and quinine compete for transport via PfCRT in a manner that is consistent with mixed-type inhibition. Moreover, our analyses suggest that PfCRT accepts chloroquine and quinine at distinct but antagonistically interacting sites. We also found verapamil to be a partial mixed-type inhibitor of chloroquine transport via PfCRT, further supporting the idea that PfCRT possesses multiple substrate-binding sites. Our findings provide new mechanistic insights into the workings of PfCRT, which could be exploited to design potent inhibitors of this key mediator of drug resistance. PMID:25378409

Evaluation of a Plasmodium-Specific Carrier Protein To Enhance Production of Recombinant Pfs25, a Leading Transmission-Blocking Vaccine Candidate.

PubMed

Parzych, Elizabeth M; Miura, Kazutoyo; Ramanathan, Aarti; Long, Carole A; Burns, James M

2018-01-01

Challenges with the production and suboptimal immunogenicity of malaria vaccine candidates have slowed the development of a Plasmodium falciparum multiantigen vaccine. Attempting to resolve these issues, we focused on the use of highly immunogenic merozoite surface protein 8 (MSP8) as a vaccine carrier protein. Previously, we showed that a genetic fusion of the C-terminal 19-kDa fragment of merozoite surface protein 1 (MSP1 19 ) to P. falciparum MSP8 ( Pf MSP8) facilitated antigen production and folding and the induction of neutralizing antibodies to conformational B cell epitopes of MSP1 19 Here, using the Pf MSP1/8 construct, we further optimized the recombinant Pf MSP8 (r Pf MSP8) carrier by the introduction of two cysteine-to-serine substitutions (CΔS) to improve the yield of the monomeric product. We then sought to test the broad applicability of this approach using the transmission-blocking vaccine candidate Pf s25. The production of r Pf s25-based vaccines has presented challenges. Antibodies directed against the four highly constrained epidermal growth factor (EGF)-like domains of Pf s25 block sexual-stage development in mosquitoes. The sequence encoding mature Pf s25 was codon harmonized for expression in Escherichia coli We produced a r Pf s25- Pf MSP8 fusion protein [r Pf s25/8(CΔS)] as well as unfused, mature r Pf s25. r Pf s25 was purified with a modest yield but required the incorporation of refolding protocols to obtain a proper conformation. In comparison, chimeric r Pf s25/8(CΔS) was expressed and easily purified, with the Pf s25 domain bearing the proper conformation without renaturation. Both antigens were immunogenic in rabbits, inducing IgG that bound native Pf s25 and exhibited potent transmission-reducing activity. These data further demonstrate the utility of Pf MSP8 as a parasite-specific carrier protein to enhance the production of complex malaria vaccine targets. Copyright © 2017 American Society for Microbiology.

The COOH-terminal peptide of platelet factor-4 variant (CXCL4L1/PF-4var47-70) strongly inhibits angiogenesis and suppresses B16 melanoma growth in vivo.

PubMed

Vandercappellen, Jo; Liekens, Sandra; Bronckaers, Annelies; Noppen, Samuel; Ronsse, Isabelle; Dillen, Chris; Belleri, Mirella; Mitola, Stefania; Proost, Paul; Presta, Marco; Struyf, Sofie; Van Damme, Jo

2010-03-01

Chemokines influence tumor growth directly or indirectly via both angiogenesis and tumor-leukocyte interactions. Platelet factor-4 (CXCL4/PF-4), which is released from alpha-granules of activated platelets, is the first described angiostatic chemokine. Recently, it was found that the variant of CXCL4/PF-4 (CXCL4L1/PF-4var) could exert a more pronounced angiostatic and antitumoral effect than CXCL4/PF-4. However, the molecular mechanisms of the angiostatic activities of the PF-4 forms remain partially elusive. Here, we studied the biological properties of the chemically synthesized COOH-terminal peptides of CXCL4/PF-4 (CXCL4/PF-4(47-70)) and CXCL4L1/PF-4var (CXCL4L1/PF-4var(47-70)). Both PF-4 peptides lacked monocyte and lymphocyte chemotactic activity but equally well inhibited (25 nmol/L) endothelial cell motility and proliferation in the presence of a single stimulus (i.e., exogenous recombinant fibroblast growth factor-2). In contrast, when assayed in more complex angiogenesis test systems characterized by the presence of multiple mediators, including in vitro wound-healing (2.5 nmol/L versus 12.5 nmol/L), Matrigel (60 nmol/L versus 300 nmol/L), and chorioallantoic membrane assays, CXCL4L1/PF-4var(47-70) was found to be significantly (5-fold) more angiostatic than CXCL4/PF-4(47-70). In addition, low (7 microg total) doses of intratumoral CXCL4L1/PF-4var(47-70) inhibited B16 melanoma growth in mice more extensively than CXCL4/PF-4(47-70). This antitumoral activity was predominantly mediated through inhibition of angiogenesis (without affecting blood vessel stability) and induction of apoptosis, as evidenced by immunohistochemical and fluorescent staining of B16 tumor tissue. In conclusion, CXCL4L1/PF-4var(47-70) is a potent antitumoral and antiangiogenic peptide. These results may represent the basis for the design of CXCL4L1/PF-4var COOH-terminal-derived peptidomimetic anticancer drugs.

A critical period for functional vestibular development in zebrafish

NASA Technical Reports Server (NTRS)

Moorman, Stephen J.; Cordova, Rodolfo; Davies, Sarah A.

2002-01-01

We have determined a critical period for vestibular development in zebrafish by using a bioreactor designed by NASA to simulate microgravity for cells in culture. A critical period is defined as the briefest period of time during development when stimulus deprivation results in long lasting or permanent sensory deficits. Zebrafish eggs were collected within 3 hours of being laid and fertilized. In experiment 1, eggs were placed in the bioreactor at 3, 24, 30, 36, 48, or 72 hours postfertilization (hPF) and maintained in the bioreactor until 96 hPF. In experiment 2, eggs were placed in the bioreactor immediately after they were collected and maintained in the bioreactor until 24, 36, 48, 60, 66, 72, or 96 hPF. Beginning at 96 hPF, all larvae had their vestibulo-ocular reflexes (VOR) evaluated once each day for 5 days. Only larvae that hatched from eggs that were placed in the bioreactor before 30 hPF in experiment 1 or removed from the bioreactor later than 66 hPF in experiment 2 had VOR deficits that persisted for at least 5 days. These data suggest a critical period for vestibular development in the zebrafish that begins before 30 hPF and ends after 66 hPF. To confirm this, zebrafish eggs were placed in the bioreactor at 24 hPF and removed at 72 hPF. VORs were evaluated in these larvae once each day for 5 days beginning at 96 hPF. These larvae had VOR deficits that persisted for at least 5 days. In addition, larvae that had been maintained in the bioreactor from 24 to 66 hPF or from 30 to 72 hPF, had only temporary VOR deficits. In a final experiment, zebrafish eggs were placed in the bioreactor at 3 hPF and removed at 96 hPF but the bioreactor was turned off from 24 hPF to 72 hPF. These larvae had normal VORs when they were removed from the bioreactor at 96 hPF. Taken as a whole, these data support the idea that there is a critical period for functional maturation of the zebrafish vestibular system. The developmental period identified includes the timeframe during which the vestibular primary afferent neurons are born, innervate their central and peripheral targets, and remodel their central projections. Copyright 2002 Wiley-Liss, Inc.

Effects of peritoneal fluid from endometriosis patients on the release of monocyte-specific chemokines by leukocytes.

PubMed

Na, Yong-Jin; Lee, Dong-Hyung; Kim, Seung-Chul; Joo, Jong-Kil; Wang, Ji-Won; Jin, Jun-O; Kwak, Jong-Young; Lee, Kyu-Sup

2011-06-01

Chemokines have been implicated in the pathological process of endometriosis. We compared the effects of peritoneal fluid obtained from patients with endometriosis (ePF) and controls without endometriosis (cPF) on the release of monocyte-specific CC chemokines such as monocyte chemotactic protein-1 (MCP-1), regulated upon activation normal T cell expressed and secreted (RANTES), and macrophage inflammatory protein-1α (MIP-1α) by neutrophils, monocytes, and T cells. Moreover, we evaluated the correlation between the levels of chemokines in ePF and their release by these cells. Cells were obtained from healthy young volunteers and cultured with ePF (n = 12) or cPF (n = 8). The chemokine levels in the ePF and the supernatants of cultured cells with ePF were then measured by ELISA. There was a positive correlation between the levels of MCP-1 and MIP-1α in ePF. The addition of ePF to the cell cultures failed to increase the release of MCP-1, RANTES, and MIP-1α when compared to cPF, but the levels of RANTES in ePF were positively correlated with the release of RANTES by ePF-treated monocytes and T cells. Moreover, there was a positive correlation between the levels of RANTES and MIP-1α released by neutrophils and between the levels of MCP-1 and MIP-1α released by T cells. Finally, the levels of RANTES released by monocyte-derived macrophages and monocytes cultured with ePF were positively correlated. These findings suggest that monocytes, neutrophils, and T cells release differential levels of MCP-1, RANTES, and MIP-1α in response to stimulation with ePF.

Implications of Parasites Lacking Plasmodium falciparum Histidine-Rich Protein 2 on Malaria Morbidity and Control When Rapid Diagnostic Tests Are Used for Diagnosis.

PubMed

Gatton, Michelle L; Dunn, Jessica; Chaudhry, Alisha; Ciketic, Sadmir; Cunningham, Jane; Cheng, Qin

2017-04-01

Rapid diagnostic tests (RDTs) are an important tool for malaria diagnosis, with most using antibodies against Plasmodium falciparum histidine-rich protein 2 (PfHRP2). Reports of P. falciparum lacking this protein are increasing, creating a problem for diagnosis of falciparum malaria in locations without quality-assured microscopy. An agent-based stochastic simulation model of P. falciparum transmission was used to investigate the selective pressure exerted on parasite populations by use of RDTs for diagnosis of symptomatic cases. The model considered parasites with normal, reduced, or no PfHRP2, and diagnosis using PfHRP2-only or combination RDTs. Use of PfHRP2-only RDTs in communities where a PfHRP2-negative parasite was introduced during the simulation resulted in transmission of the parasite in >80% of cases, compared with <30% for normal or PfHRP2-reduced parasites. Using PfHRP2-only RDTs in the presence of PfHRP2-negative parasites caused an increase in prevalence, reduced RDT positivity within symptomatic patients but no change in the number of antimalarial treatments due to false-negative RDT results. Diagnosis with PfHRP2/Pf-Plasmodium lactate dehydrogenase combination RDTs did not select for PfHRP2-negative parasites. The use of PfHRP2-only RDTs is sufficient to select P. falciparum parasites lacking this protein, thus posing a significant public health problem, which could be moderated by using PfHRP2/Pf-Plasmodium lactate dehydrogenase combination RDTs. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Expansion of a physical function item bank and development of an abbreviated form for clinical research.

PubMed

Bode, Rita K; Lai, Jin-shei; Dineen, Kelly; Heinemann, Allen W; Shevrin, Daniel; Von Roenn, Jamie; Cella, David

2006-01-01

We expanded an existing 33-item physical function (PF) item bank with a sufficient number of items to enable computerized adaptive testing (CAT). Ten items were written to expand the bank and the new item pool was administered to 295 people with cancer. For this analysis of the new pool, seven poorly performing items were identified for further examination. This resulted in a bank with items that define an essentially unidimensional PF construct, cover a wide range of that construct, reliably measure the PF of persons with cancer, and distinguish differences in self-reported functional performance levels. We also developed a 5-item (static) assessment form ("BriefPF") that can be used in clinical research to express scores on the same metric as the overall bank. The BriefPF was compared to the PF-10 from the Medical Outcomes Study SF-36. Both short forms significantly differentiated persons across functional performance levels. While the entire bank was more precise across the PF continuum than either short form, there were differences in the area of the continuum in which each short form was more precise: the BriefPF was more precise than the PF-10 at the lower functional levels and the PF-10 was more precise than the BriefPF at the higher levels. Future research on this bank will include the development of a CAT version, the PF-CAT.

Pf155/RESA protein influences the dynamic microcirculatory behavior of ring-stage Plasmodium falciparum infected red blood cells

PubMed Central

Diez-Silva, Monica; Park, YongKeun; Huang, Sha; Bow, Hansen; Mercereau-Puijalon, Odile; Deplaine, Guillaume; Lavazec, Catherine; Perrot, Sylvie; Bonnefoy, Serge; Feld, Michael S.; Han, Jongyoon; Dao, Ming; Suresh, Subra

2012-01-01

Proteins exported by Plasmodium falciparum to the red blood cell (RBC) membrane modify the structural properties of the parasitized RBC (Pf-RBC). Although quasi-static single cell assays show reduced ring-stage Pf-RBCs deformability, the parameters influencing their microcirculatory behavior remain unexplored. Here, we study the dynamic properties of ring-stage Pf-RBCs and the role of the parasite protein Pf155/Ring-Infected Erythrocyte Surface Antigen (RESA). Diffraction phase microscopy revealed RESA-driven decreased Pf-RBCs membrane fluctuations. Microfluidic experiments showed a RESA-dependent reduction in the Pf-RBCs transit velocity, which was potentiated at febrile temperature. In a microspheres filtration system, incubation at febrile temperature impaired traversal of RESA-expressing Pf-RBCs. These results show that RESA influences ring-stage Pf-RBCs microcirculation, an effect that is fever-enhanced. This is the first identification of a parasite factor influencing the dynamic circulation of young asexual Pf-RBCs in physiologically relevant conditions, offering novel possibilities for interventions to reduce parasite survival and pathogenesis in its human host. PMID:22937223

Pf155/RESA protein influences the dynamic microcirculatory behavior of ring-stage Plasmodium falciparum infected red blood cells

NASA Astrophysics Data System (ADS)

Diez-Silva, Monica; Park, Yongkeun; Huang, Sha; Bow, Hansen; Mercereau-Puijalon, Odile; Deplaine, Guillaume; Lavazec, Catherine; Perrot, Sylvie; Bonnefoy, Serge; Feld, Michael S.; Han, Jongyoon; Dao, Ming; Suresh, Subra

2012-08-01

Proteins exported by Plasmodium falciparum to the red blood cell (RBC) membrane modify the structural properties of the parasitized RBC (Pf-RBC). Although quasi-static single cell assays show reduced ring-stage Pf-RBCs deformability, the parameters influencing their microcirculatory behavior remain unexplored. Here, we study the dynamic properties of ring-stage Pf-RBCs and the role of the parasite protein Pf155/Ring-Infected Erythrocyte Surface Antigen (RESA). Diffraction phase microscopy revealed RESA-driven decreased Pf-RBCs membrane fluctuations. Microfluidic experiments showed a RESA-dependent reduction in the Pf-RBCs transit velocity, which was potentiated at febrile temperature. In a microspheres filtration system, incubation at febrile temperature impaired traversal of RESA-expressing Pf-RBCs. These results show that RESA influences ring-stage Pf-RBCs microcirculation, an effect that is fever-enhanced. This is the first identification of a parasite factor influencing the dynamic circulation of young asexual Pf-RBCs in physiologically relevant conditions, offering novel possibilities for interventions to reduce parasite survival and pathogenesis in its human host.

The role of the CXC chemokines platelet factor-4 (CXCL4/PF-4) and its variant (CXCL4L1/PF-4var) in inflammation, angiogenesis and cancer.

PubMed

Vandercappellen, Jo; Van Damme, Jo; Struyf, Sofie

2011-02-01

Chemokines are chemotactic cytokines which recruit leukocytes to inflammatory sites. They also affect tumor development and metastasis by acting as growth factor, by attracting pro- or anti-tumoral leukocytes or by influencing angiogenesis. Platelet factor-4 (CXCL4/PF-4) was the first chemokine shown to inhibit angiogenesis. CXCL4L1/PF-4var, recently isolated from thrombin-stimulated platelets, differing from authentic CXCL4/PF-4 in three carboxy-terminally located amino acids, was found to be more potent than CXCL4/PF-4 in inhibiting angiogenesis and tumor growth. Both glycosaminoglycans (GAG) and CXCR3 are implicated in the activities of the PF-4 variants. This report reviews the current knowledge on the role of CXCL4/PF-4 and CXCL4L1/PF-4var in physiological and pathological processes. In particular, the role of CXCL4/PF-4 in cancer, heparin-induced thrombocytopenia and atherosclerosis is described. Copyright © 2010 Elsevier Ltd. All rights reserved.

Controlled Human Malaria Infection of Tanzanians by Intradermal Injection of Aseptic, Purified, Cryopreserved Plasmodium falciparum Sporozoites

PubMed Central

Shekalaghe, Seif; Rutaihwa, Mastidia; Billingsley, Peter F.; Chemba, Mwajuma; Daubenberger, Claudia A.; James, Eric R.; Mpina, Maximillian; Ali Juma, Omar; Schindler, Tobias; Huber, Eric; Gunasekera, Anusha; Manoj, Anita; Simon, Beatus; Saverino, Elizabeth; Church, L. W. Preston; Hermsen, Cornelus C.; Sauerwein, Robert W.; Plowe, Christopher; Venkatesan, Meera; Sasi, Philip; Lweno, Omar; Mutani, Paul; Hamad, Ali; Mohammed, Ali; Urassa, Alwisa; Mzee, Tutu; Padilla, Debbie; Ruben, Adam; Lee Sim, B. Kim; Tanner, Marcel; Abdulla, Salim; Hoffman, Stephen L.

2014-01-01

Controlled human malaria infection (CHMI) by mosquito bite has been used to assess anti-malaria interventions in > 1,500 volunteers since development of methods for infecting mosquitoes by feeding on Plasmodium falciparum (Pf) gametocyte cultures. Such CHMIs have never been used in Africa. Aseptic, purified, cryopreserved Pf sporozoites, PfSPZ Challenge, were used to infect Dutch volunteers by intradermal injection. We conducted a double-blind, placebo-controlled trial to assess safety and infectivity of PfSPZ Challenge in adult male Tanzanians. Volunteers were injected intradermally with 10,000 (N = 12) or 25,000 (N = 12) PfSPZ or normal saline (N = 6). PfSPZ Challenge was well tolerated and safe. Eleven of 12 and 10 of 11 subjects, who received 10,000 and 25,000 PfSPZ respectively, developed parasitemia. In 10,000 versus 25,000 PfSPZ groups geometric mean days from injection to Pf positivity by thick blood film was 15.4 versus 13.5 (P = 0.023). Alpha-thalassemia heterozygosity had no apparent effect on infectivity. PfSPZ Challenge was safe, well tolerated, and infectious. PMID:25070995

Anti-Plasmodium falciparum invasion ligand antibodies in a low malaria transmission region, Loreto, Peru

PubMed Central

2012-01-01

Background Erythrocyte invasion by Plasmodium falciparum is a complex process that involves two families; Erythrocyte Binding-Like (EBL) and the Reticulocyte Binding-Like (PfRh) proteins. Antibodies that inhibit merozoite attachment and invasion are believed to be important in mediating naturally acquired immunity and immunity generated by parasite blood stage vaccine candidates. The hypotheses tested in this study were 1) that antibody responses against specific P. falciparum invasion ligands (EBL and PfRh) differ between symptomatic and asymptomatic individuals living in the low-transmission region of the Peruvian Amazon and 2), such antibody responses might have an association, either direct or indirect, with clinical immunity observed in asymptomatically parasitaemic individuals. Methods ELISA was used to assess antibody responses (IgG, IgG1 and IgG3) against recombinant P. falciparum invasion ligands of the EBL (EBA-175, EBA-181, EBA-140) and PfRh families (PfRh1, PfRh2a, PfRh2b, PfRh4 and PfRh5) in 45 individuals infected with P. falciparum from Peruvian Amazon. Individuals were classified as having symptomatic malaria (N=37) or asymptomatic infection (N=8). Results Antibody responses against both EBL and PfRh family proteins were significantly higher in asymptomatic compared to symptomatic individuals, demonstrating an association with clinical immunity. Significant differences in the total IgG responses were observed with EBA-175, EBA-181, PfRh2b, and MSP119 (as a control). IgG1 responses against EBA-181, PfRh2a and PfRh2b were significantly higher in the asymptomatic individuals. Total IgG antibody responses against PfRh1, PfRh2a, PfRh2b, PfRh5, EBA-175, EBA-181 and MSP119 proteins were negatively correlated with level of parasitaemia. IgG1 responses against EBA-181, PfRh2a and PfRh2b and IgG3 response for PfRh2a were also negatively correlated with parasitaemia. Conclusions These data suggest that falciparum malaria patients who develop clinical immunity (asymptomatic parasitaemia) in a low transmission setting such as the Peruvian Amazon have antibody responses to defined P. falciparum invasion ligand proteins higher than those found in symptomatic (non-immune) patients. While these findings will have to be confirmed by larger studies, these results are consistent with a potential role for one or more of these invasion ligands as a component of an anti-P. falciparum vaccine in low-transmission malaria-endemic regions. PMID:23110555

Downhole transmission system

DOEpatents

Hall, David R [Provo, UT; Fox, Joe [Spanish Fork, UT

2008-01-15

A transmission system in a downhole component comprises a data transmission element in both ends of the downhole component. Each data transmission element houses an electrically conducting coil in a MCEI circular trough. An electrical conductor connects both the transmission elements. The electrical conductor comprises at least three electrically conductive elements insulated from each other. In the preferred embodiment the electrical conductor comprises an electrically conducting outer shield, an electrically conducting inner shield and an electrical conducting core. In some embodiments of the present invention, the electrical conductor comprises an electrically insulating jacket. In other embodiments, the electrical conductor comprises a pair of twisted wires. In some embodiments, the electrical conductor comprises semi-conductive material.

Development of internal magnetic probe for current density profile measurement in Versatile Experiment Spherical Torus

NASA Astrophysics Data System (ADS)

Yang, J.; Lee, J. W.; Jung, B. K.; Chung, K. J.; Hwang, Y. S.

2014-11-01

An internal magnetic probe using Hall sensors to measure a current density profile directly with perturbation of less than 10% to the plasma current is successfully operated for the first time in Versatile Experiment Spherical Torus (VEST). An appropriate Hall sensor is chosen to produce sufficient signals for VEST magnetic field while maintaining the small size of 10 mm in outer diameter. Temperature around the Hall sensor in a typical VEST plasma is regulated by blown air of 2 bars. First measurement of 60 kA VEST ohmic discharge shows a reasonable agreement with the total plasma current measured by Rogowski coil in VEST.

Development of fisetin-loaded folate functionalized pluronic micelles for breast cancer targeting.

PubMed

Pawar, Atmaram; Singh, Srishti; Rajalakshmi, S; Shaikh, Karimunnisa; Bothiraja, C

2018-01-15

The natural flavonoid fisetin (FS) has shown anticancer properties but its in-vivo administration remains challenging due to its poor aqueous solubility. The aim of the study was to develop FS loaded pluronic127 (PF)-folic acid (FA) conjugated micelles (FS-PF-FA) by the way of increasing solubility, bioavailability and active targetability of FS shall increase its therapeutic efficacy. FA-conjugated PF was prepared by carbodiimide crosslinker chemistry. FS-PF-FA micelles were prepared by thin-film hydration method and evaluated in comparison with free FS and FS loaded PF micelles (FS-PF). The smooth surfaces with spherical in shape of FS-PF-PF micelles displayed smaller in size (103.2 ± 6.1 nm), good encapsulation efficiency (82.50 ± 1.78%), zeta potential (-26.7 ± 0.44 mV) and sustained FS release. Bioavailability of FS from FS-PF-PF micelles was increased by 6-fold with long circulation time, slower plasma elimination and no sign of tissue toxicity as compared to free FS. Further, the FS-PF-FA micelles demonstrated active targeting effect on folate overexpressed human breast cancer MCF-7 cells. The concentration of the drug needed for growth inhibition of 50% of cells in a designed time period (GI50) was 14.3 ± 1.2 µg/ml for FS while it was greatly decreased to 9.8 ± 0.78 µg/ml, i.e. a 31.46% decrease for the FS-PF. Furthermore, the GI50 value for FS-PF-FA was 4.9 ± 0.4 µg/ml, i.e. a 65.737% decrease compared to FS and 50% decrease compare to FS-PF. The results indicate that the FS-PF-FA micelles have the potential to be applied for targeting anticancer drug delivery.

Targeting colorectal cancer cells by a novel sphingosine kinase 1 inhibitor PF-543

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

Ju, TongFa; Gao, DaQuan; Fang, Zheng-yu, E-mail: fangzhengyu158@sina.com

In this study, we showed that PF-543, a novel sphingosine kinase 1 (SphK1) inhibitor, exerted potent anti-proliferative and cytotoxic effects against a panel of established (HCT-116, HT-29 and DLD-1) and primary human colorectal cancer (CRC) cells. Its sensitivity was negatively associated with SphK1 expression level in the CRC cells. Surprisingly, PF-543 mainly induced programmed necrosis, but not apoptosis, in the CRC cells. CRC cell necrotic death was detected by lactate dehydrogenase (LDH) release, mitochondrial membrane potential (MMP) collapse and mitochondrial P53-cyclophilin-D (Cyp-D) complexation. Correspondingly, the necrosis inhibitor necrostatin-1 largely attenuated PF-543-induced cytotoxicity against CRC cells. Meanwhile, the Cyp-D inhibitors (sanglifehrinmore » A and cyclosporin A), or shRNA-mediated knockdown of Cyp-D, remarkably alleviated PF-543-induced CRC cell necrotic death. Reversely, over-expression of wild-type Cyp-D in HCT-116 cells significantly increased PF-543's sensitivity. In vivo, PF-543 intravenous injection significantly suppressed HCT-116 xenograft growth in severe combined immunodeficient (SCID) mice, whiling remarkably improving the mice survival. The in vivo activity by PF-543 was largely attenuated when combined with the Cyp-D inhibitor cyclosporin A. Collectively, our results demonstrate that PF-543 exerts potent anti-CRC activity in vitro and in vivo. Mitochondrial programmed necrosis pathway is likely the key mechanism responsible for PF-543's actions in CRC cells. - Highlights: • PF-543 is anti-proliferative and cytotoxic to established and primary CRC cells. • PF-543 induces programmed necrosis, but not apoptosis, in CRC cells. • Modulation of mitochondrial protein cyclophilin-D alters PF-543's sensitivity. • PF-543 inhibits HCT-116 xenograft growth in SCID mice, improving mice survival. • Co-administration of cyclophilin-D inhibitor CsA inhibits PF-543's activity in vivo.« less

Pelvis width associated with bone mass distribution at the proximal femur in children 10–11 years old

PubMed Central

Cardadeiro, Graça; Baptista, Fátima; Janz, Kathleen F.; Rodrigues, Luís A.; Sardinha, Luís B.

2015-01-01

Differences in skeletal geometry may generate different patterns of mechanical loading to bone. Impact and muscle loading during physical activity have been shown to influence skeletal geometry. The purpose of this study was to compare geometric measures of the pelvis and proximal femur (PF) of young children and to analyze the contribution and potential interaction of these geometric measures with physical activity on PF bone mass distribution. Participants were 149 girls and 145 boys, aged 10–11 years. Total body and left hip DXA scans were used to derive pelvic and PF geometric measures and PF bone mineral density (BMD) at the femoral neck (FN), trochanter (TR), and intertrochanter (IT). These subregions were used to represent bone mass distribution via three BMD ratios: FN:PF, TR:PF, and IT:PF. Physical activity was objectively measured using accelerometry, and maturity was estimated as the years of distance from peak height velocity. When compared to boys, girls had a wider pelvic diameter and greater interacetabular distances (p < 0.001), lower BMD at FN, TR, and IT (p < 0.05), and higher TR:PF (p < 0.001). After controlling for maturity, body height, and lean body mass, the interacetabular distance in girls explained 21.1 % (β = 0.713, p < 0.001) in TR:PF and 2.9 % (β = −0.179, p = 0.031) in the IT:PF. Neck–shaft angle explained 5.6 % (β = −0.265, p = 0.001) of the IT:PF and 3.1 % (β = 0.194, p = 0.018) of the FN:PF. In boys, FN axis length explained 2.9 % (β = 0.195, p = 0.040) of TR:PF. There was no main effect of physical activity or interaction effect with pelvic geometry in explaining BMD differences among the subregions of the PF. Even before sexual dimorphism, girls have a wider pelvis than boys, which accounted for proportionally greater BMD of the TR than other subregions of the PF. PMID:23744478

Clinical characteristics of fulminant type 1 diabetes associated with pregnancy in China.

PubMed

Liu, Lan; Mao, Jiping; Lu, Zeyuan; Yan, Xiaojie; Bai, Xiaosu; Ye, Yiyi; Zou, Gang

2011-12-01

To report 12 cases of pregnancy-associated fulminant type 1 diabetes mellitus (PF) found in China from 2003 to 2010. The clinical and biochemical characteristics of these cases with PF were compared with a group of cases of child-bearing age with fulminant type 1 diabetes that was not associated with pregnancy (NPF). The clinical and biochemical characteristics of 12 PF cases were analyzed retrospectively and then compared with those characteristics of 20 NPF cases in China. The difference between Chinese and Japanese PF cases was investigated. The mean values of the characteristics from PF and NPF cases in China, including postprandial serum C-peptide concentration, plasma glucose concentration, and serum chloride were different. Compared to the 22 PF cases in Japan, the mean age of these 12 PF cases was much younger. The mean fasting and postprandial serum C-peptide concentration level were lower, and the mean HbA1c levels was higher in 12 PF cases in China. Eight of 12 PF cases in China developed the disease during pregnancy. Other four PF case developed the disease within 2 weeks after delivery. 12 PF cases in China showed more severe beta-cell destruction, the prognosis of their fetuses was extremely poor.

Atomic description of the immune complex involved in heparin-induced thrombocytopenia

DOE PAGES

Cai, Zheng; Yarovoi, Serge V.; Zhu, Zhiqiang; ...

2015-09-22

Heparin-induced thrombocytopenia (HIT) is an autoimmune thrombotic disorder caused by immune complexes containing platelet factor 4 (PF4), antibodies to PF4 and heparin or cellular glycosaminoglycans (GAGs). Here we solve the crystal structures of the: (1) PF4 tetramer/fondaparinux complex, (2) PF4 tetramer/KKO-Fab complex (a murine monoclonal HIT-like antibody) and (3) PF4 monomer/RTO-Fab complex (a non-HIT anti-PF4 monoclonal antibody). Fondaparinux binds to the ‘closed’ end of the PF4 tetramer and stabilizes its conformation. This interaction in turn stabilizes the epitope for KKO on the ‘open’ end of the tetramer. Fondaparinux and KKO thereby collaborate to ‘stabilize’ the ternary pathogenic immune complex. Bindingmore » of RTO to PF4 monomers prevents PF4 tetramerization and inhibits KKO and human HIT IgG-induced platelet activation and platelet aggregation in vitro, and thrombus progression in vivo. Lastly, the atomic structures provide a basis to develop new diagnostics and non-anticoagulant therapeutics for HIT.« less

Solvate Structures and Computational/Spectroscopic Characterization of LiPF6 Electrolytes

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

Han, Sang D.; Yun, Sung-Hyun; Borodin, Oleg

2015-04-23

Raman spectroscopy is a powerful method for identifying ion-ion interactions, but only if the vibrational band signature for the anion coordination modes can be accurately deciphered. The present study characterizes the PF6- anion P-F Raman symmetric stretching vibrational band for evaluating the PF6-...Li+ cation interactions within LiPF6 crystalline solvates to create a characterization tool for liquid electrolytes. To facilitate this, the crystal structures for two new solvates—(G3)1:LiPF6 and (DEC)2:LiPF6 with triglyme and diethyl carbonate, respectively—are reported. The information obtained from this analysis provides key guidance about the ionic association information which may be obtained from a Raman spectroscopic evaluation ofmore » electrolytes containing the LiPF6 salt and aprotic solvents. Of particular note is the overlap of the Raman bands for both solvent-separated ion pair (SSIP) and contact ion pair (CIP) coordination in which the PF6- anions are uncoordinated or coordinated to a single Li+ cation, respectively.« less

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

Cai, Zheng; Yarovoi, Serge V.; Zhu, Zhiqiang

Heparin-induced thrombocytopenia (HIT) is an autoimmune thrombotic disorder caused by immune complexes containing platelet factor 4 (PF4), antibodies to PF4 and heparin or cellular glycosaminoglycans (GAGs). Here we solve the crystal structures of the: (1) PF4 tetramer/fondaparinux complex, (2) PF4 tetramer/KKO-Fab complex (a murine monoclonal HIT-like antibody) and (3) PF4 monomer/RTO-Fab complex (a non-HIT anti-PF4 monoclonal antibody). Fondaparinux binds to the ‘closed’ end of the PF4 tetramer and stabilizes its conformation. This interaction in turn stabilizes the epitope for KKO on the ‘open’ end of the tetramer. Fondaparinux and KKO thereby collaborate to ‘stabilize’ the ternary pathogenic immune complex. Bindingmore » of RTO to PF4 monomers prevents PF4 tetramerization and inhibits KKO and human HIT IgG-induced platelet activation and platelet aggregation in vitro, and thrombus progression in vivo. Lastly, the atomic structures provide a basis to develop new diagnostics and non-anticoagulant therapeutics for HIT.« less

Plasmodium falciparum signal peptide peptidase cleaves malaria heat shock protein 101 (HSP101). Implications for gametocytogenesis

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

Baldwin, Michael; Russo, Crystal; Li, Xuerong

Highlights: • PfSPP is an ER resident protease. • PfSPP is expressed both as a monomer and dimer. • The signal peptide of HSP101 is the first known substrate of PfSPP. • Reduced PfSPP activity may significantly affect ER homeostasis. - Abstract: Previously we described the identification of a Plasmodium falciparum signal peptide peptidase (PfSPP) functioning at the blood stage of malaria infection. Our studies also demonstrated that mammalian SPP inhibitors prevent malaria parasite growth at the late-ring/early trophozoite stage of intra-erythrocytic development. Consistent with its role in development, we tested the hypothesis that PfSPP functions at the endoplasmic reticulummore » of P.falciparum where it cleaves membrane-bound signal peptides generated following the enzyme activity of signal peptidase. The localization of PfSPP to the endoplasmic reticulum was confirmed by immunofluorescence microscopy and immunogold electron microscopy. Biochemical analysis indicated the existence of monomer and dimer forms of PfSPP in the parasite lysate. A comprehensive bioinformatics screen identified several candidate PfSPP substrates in the parasite genome. Using an established transfection based in vivo luminescence assay, malaria heat shock protein 101 (HSP101) was identified as a substrate of PfSPP, and partial inhibition of PfSPP correlated with the emergence of gametocytes. This finding unveils the first known substrate of PfSPP, and provides new perspectives for the function of intra-membrane proteolysis at the erythrocyte stage of malaria parasite life cycle.« less

Molecular identification of lipase LipA from Pseudomonas protegens Pf-5 and characterization of two whole-cell biocatalysts Pf-5 and Top10lipA.

PubMed

Zha, Daiming; Xu, Li; Zhang, Houjin; Yan, Yunjun

2014-05-01

To identify lipase LipA (PFL_0617) from Pseudomonas protegens Pf-5, a lipA deletion mutant (Pf0617) and a complementary strain (Pf0617lipA) were constructed, and their effects on the lipase production were examined. Pf0617 remarkably decreased its whole-cell lipase activity, whereas Pf0617lipA made its whole-cell lipase activity not only restore to wild-type level but also get a further increment. However, the deletion and overexpression of lipA did not affect the extracellular lipase activity. In addition, the unbroken whole cells of these strains were able to catalyze the hydrolysis of membrane-permeable p-nitrophenyl esters, but could not hydrolyze the membrane-impermeable olive oil. These results confirmed that LipA was an intracellular lipase and Pf-5 could also be used as a natural whole-cell biocatalyst. To evaluate the potential of Pf-5 as a whole-cell biocatalyst and separately characterize the whole-cell LipA, the properties of the whole-cell lipases from Pf-5 and Top10lipA were characterized. The results demonstrated that both Pf-5 and Top10lipA exhibited high tolerance to alkaline condition, high temperature, heavy metal ions, surfactants, and organic solvents. Taken together, lipA can realize functional expression in E. coli Top10, and Pf-5 and Top10lipA as whole-cell biocatalysts may have enormous potential in applications.

Paeoniflorin inhibits cell growth and induces cell cycle arrest through inhibition of FoxM1 in colorectal cancer cells.

PubMed

Yue, Meng; Li, Shiquan; Yan, Guoqiang; Li, Chenyao; Kang, Zhenhua

2018-01-01

Paeoniflorin (PF) exhibits tumor suppressive functions in a variety of human cancers. However, the function of PF and molecular mechanism in colorectal cancer are elusive. In the present study, we investigated whether PF could exert its antiproliferative activity, anti-migration, and anti-invasive function in colorectal cancer cells. We found that PF inhibited cell growth and induced apoptosis and blocked cell cycle progression in the G0/G1 phase in colorectal cancer cells. Moreover, we found that PF suppressed cell migration and invasion in colorectal cancer cells. FoxM1 has been reported to play an important oncogenic role in human cancers. We also determine whether PF inhibited the expression of FoxM1, leading to its anti-cancer activity. We found that PF treatment in colorectal cancer cells resulted in down-regulation of FoxM1. The rescue experiments showed that overexpression of FoxM1 abrogated the tumor suppressive function induced by PF treatment. Notably, depletion of FoxM1 promoted the anti-tumor activity of PF in colorectal cancer cells. Therefore, inhibition of FoxM1 could participate in the anti-tumor activity of PF in colorectal cancer cells.

PfSMAD4 plays a role in biomineralization and can transduce bone morphogenetic protein-2 signals in the pearl oyster Pinctada fucata.

PubMed

Zhao, Mi; Shi, Yu; He, Maoxian; Huang, Xiande; Wang, Qi

2016-04-26

Mollusca is the second largest phylum in nature. The shell of molluscs is a remarkable example of a natural composite biomaterial. Biomineralization and how it affects mollusks is a popular research topic. The BMP-2 signaling pathway plays a canonical role in biomineralization. SMAD4 is an intracellular transmitter in the BMP signaling pathway in mammals, and some genomic data show SMAD4's involvement in BMP signaling in invertebrates, but whether SMAD4 plays a conservative role in pearl oyster, Pinctada fucata, still need to be tested. In this study, we identified a SMAD4 gene (hereafter designated PfSMAD4) in pearl oyster Pinctada fucata. Bioinformatics analysis of PfSMAD4 showed high identity with its orthologs. PfSMAD4 was located in the cytoplasm in immunofluorescence assays and analyses of PfSMAD4 mRNA in tissues and developmental stages showed high expression in ovaries and D-shaped larvae. An RNA interference experiment, performed by PfSMAD4 double-stranded RNA (dsRNA) injection, demonstrated inhibition not only of nacre growth but also organic sheet formation with a decrease in PfSMAD4 expression. A knockdown experiment using PfBMP2 dsRNA showed decreased PfBMP2 and PfSMAD4 mRNA and irregular crystallization of the nacreous layer using scanning electron microscopy. In co-transfection experiments, PfBMP2-transactivated reporter constructs contained PfSMAD4 promoter sequences. Our results suggest that PfSMAD4 plays a role in biomineralization and can transduce BMP signals in P. fucata. Our data provides important clues about the molecular mechanisms that regulate biomineralization in pearl oyster.

Preference for Solitude, Social Isolation, Suicidal Ideation, and Self-Harm in Adolescents.

PubMed

Endo, Kaori; Ando, Shuntaro; Shimodera, Shinji; Yamasaki, Syudo; Usami, Satoshi; Okazaki, Yuji; Sasaki, Tsukasa; Richards, Marcus; Hatch, Stephani; Nishida, Atsushi

2017-08-01

Social isolation is associated with suicidal ideation (SI) and self-harm (SH) among adolescents. However, the association between preference for solitude (PfS), SI, and SH is unknown. The prevalence of adolescents who have both of PfS and social isolation and the risks for SI and SH among them are also unknown. Information on PfS, social isolation, SI, and SH was collected in a large-scale school-based survey on adolescents, using a self-report questionnaire. Associations between PfS, SI, and SH were examined by logistic regression analysis. The interactions between PfS and social isolation on SI and SH were also investigated. The odds of SI and SH were examined for groups defined by presence of PfS and social isolation. Responses from 17,437 students (89.3% of relevant classes) were available. After adjusting for demographic characteristics and social isolation, PfS was associated with increased odds of SI (odds ratio [OR] = 3.1) and SH (OR = 1.9). There was no interaction between PfS and social isolation on SI and SH. After adjusting for demographic characteristics, the odds for SI (OR = 8.6) and SH (OR = 3.8) were highest among adolescents with both PfS and social isolation (8.4% of all respondents). PfS was associated with increased odds of SI and SH in adolescents. No interaction effect between PfS and social isolation on SI and SH was found, but adolescents with PfS and social isolation had the highest risk for SI and SH. Parents and professionals should pay attention to suicide risk in adolescents with PfS. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Progress with Plasmodium falciparum sporozoite (PfSPZ)-based malaria vaccines.

PubMed

Richie, Thomas L; Billingsley, Peter F; Sim, B Kim Lee; James, Eric R; Chakravarty, Sumana; Epstein, Judith E; Lyke, Kirsten E; Mordmüller, Benjamin; Alonso, Pedro; Duffy, Patrick E; Doumbo, Ogobara K; Sauerwein, Robert W; Tanner, Marcel; Abdulla, Salim; Kremsner, Peter G; Seder, Robert A; Hoffman, Stephen L

2015-12-22

Sanaria Inc. has developed methods to manufacture, purify and cryopreserve aseptic Plasmodium falciparum (Pf) sporozoites (SPZ), and is using this platform technology to develop an injectable PfSPZ-based vaccine that provides high-grade, durable protection against infection with Pf malaria. Several candidate vaccines are being developed and tested, including PfSPZ Vaccine, in which the PfSPZ are attenuated by irradiation, PfSPZ-CVac, in which fully infectious PfSPZ are attenuated in vivo by concomitant administration of an anti-malarial drug, and PfSPZ-GA1, in which the PfSPZ are attenuated by gene knockout. Forty-three research groups in 15 countries, organized as the International PfSPZ Consortium (I-PfSPZ-C), are collaborating to advance this program by providing intellectual, clinical, and financial support. Fourteen clinical trials of these products have been completed in the USA, Europe and Africa, two are underway and at least 12 more are planned for 2015-2016 in the US (four trials), Germany (2 trials), Tanzania, Kenya, Mali, Burkina Faso, Ghana and Equatorial Guinea. Sanaria anticipates application to license a first generation product as early as late 2017, initially to protect adults, and a year later to protect all persons >6 months of age for at least six months. Improved vaccine candidates will be advanced as needed until the following requirements have been met: long-term protection against natural transmission, excellent safety and tolerability, and operational feasibility for population-wide administration. Here we describe the three most developed whole PfSPZ vaccine candidates, associated clinical trials, initial plans for licensure and deployment, and long-term objectives for a final product suitable for mass administration to achieve regional malaria elimination and eventual global eradication. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Attenuated PfSPZ Vaccine induces strain-transcending T cells and durable protection against heterologous controlled human malaria infection.

PubMed

Lyke, Kirsten E; Ishizuka, Andrew S; Berry, Andrea A; Chakravarty, Sumana; DeZure, Adam; Enama, Mary E; James, Eric R; Billingsley, Peter F; Gunasekera, Anusha; Manoj, Anita; Li, Minglin; Ruben, Adam J; Li, Tao; Eappen, Abraham G; Stafford, Richard E; Kc, Natasha; Murshedkar, Tooba; Mendoza, Floreliz H; Gordon, Ingelise J; Zephir, Kathryn L; Holman, LaSonji A; Plummer, Sarah H; Hendel, Cynthia S; Novik, Laura; Costner, Pamela J M; Saunders, Jamie G; Berkowitz, Nina M; Flynn, Barbara J; Nason, Martha C; Garver, Lindsay S; Laurens, Matthew B; Plowe, Christopher V; Richie, Thomas L; Graham, Barney S; Roederer, Mario; Sim, B Kim Lee; Ledgerwood, Julie E; Hoffman, Stephen L; Seder, Robert A

2017-03-07

A live-attenuated malaria vaccine, Plasmodium falciparum sporozoite vaccine (PfSPZ Vaccine), confers sterile protection against controlled human malaria infection (CHMI) with Plasmodium falciparum (Pf) parasites homologous to the vaccine strain up to 14 mo after final vaccination. No injectable malaria vaccine has demonstrated long-term protection against CHMI using Pf parasites heterologous to the vaccine strain. Here, we conducted an open-label trial with PfSPZ Vaccine at a dose of 9.0 × 10 5 PfSPZ administered i.v. three times at 8-wk intervals to 15 malaria-naive adults. After CHMI with homologous Pf parasites 19 wk after final immunization, nine (64%) of 14 (95% CI, 35-87%) vaccinated volunteers remained without parasitemia compared with none of six nonvaccinated controls ( P = 0.012). Of the nine nonparasitemic subjects, six underwent repeat CHMI with heterologous Pf7G8 parasites 33 wk after final immunization. Five (83%) of six (95% CI, 36-99%) remained without parasitemia compared with none of six nonvaccinated controls. PfSPZ-specific T-cell and antibody responses were detected in all vaccine recipients. Cytokine production by T cells from vaccinated subjects after in vitro stimulation with homologous (NF54) or heterologous (7G8) PfSPZ were highly correlated. Interestingly, PfSPZ-specific T-cell responses in the blood peaked after the first immunization and were not enhanced by subsequent immunizations. Collectively, these data suggest durable protection against homologous and heterologous Pf parasites can be achieved with PfSPZ Vaccine. Ongoing studies will determine whether protective efficacy can be enhanced by additional alterations in the vaccine dose and number of immunizations.

Progress with Plasmodium falciparum sporozoite (PfSPZ)-based malaria vaccines

PubMed Central

Richie, Thomas L.; Billingsley, Peter F.; Sim, B. Kim Lee; James, Eric R.; Chakravarty, Sumana; Epstein, Judith E.; Lyke, Kirsten E.; Mordmüller, Benjamin; Alonso, Pedro; Duffy, Patrick E.; Doumbo, Ogobara K.; Sauerwein, Robert W.; Tanner, Marcel; Abdulla, Salim; Kremsner, Peter G.; Seder, Robert A.; Hoffman, Stephen L.

2016-01-01

Sanaria Inc. has developed methods to manufacture, purify and cryopreserve aseptic Plasmodium falciparum (Pf) sporozoites (SPZ), and is using this platform technology to develop an injectable PfSPZ-based vaccine that provides high-grade, durable protection against infection with Pf malaria. Several candidate vaccines are being developed and tested, including PfSPZ Vaccine, in which the PfSPZ are attenuated by irradiation, PfSPZ-CVac, in which fully infectious PfSPZ are attenuated in vivo by concomitant administration of an anti-malarial drug, and PfSPZ-GA1, in which the PfSPZ are attenuated by gene knockout. Forty-three research groups in 15 countries, organized as the International PfSPZ Consortium (I-PfSPZ-C), are collaborating to advance this program by providing intellectual, clinical, and financial support. Fourteen clinical trials of these products have been completed in the USA, Europe and Africa, two are underway and at least 12 more are planned for 2015–2016 in the US (four trials), Germany (2 trials), Tanzania, Kenya, Mali, Burkina Faso, Ghana and Equatorial Guinea. Sanaria anticipates application to license a first generation product as early as late 2017, initially to protect adults, and a year later to protect all persons >6 months of age for at least six months. Improved vaccine candidates will be advanced as needed until the following requirements have been met: long-term protection against natural transmission, excellent safety and tolerability, and operational feasibility for population-wide administration. Here we describe the three most developed whole PfSPZ vaccine candidates, associated clinical trials, initial plans for licensure and deployment, and long-term objectives for a final product suitable for mass administration to achieve regional malaria elimination and eventual global eradication. PMID:26469720

Peritoneal fluid from endometriosis patients switches differentiation of monocytes from dendritic cells to macrophages.

PubMed

Na, Yong-Jin; Jin, Jun-O; Lee, Mi-Sook; Song, Min-Gyu; Lee, Kyu-Sup; Kwak, Jong-Young

2008-01-01

Immunological abnormalities of cell-mediated and humoral immunity might be associated with the pathogenesis of endometriosis. This study has examined the effects of peritoneal fluid obtained from patients with endometriosis (ePF) on the phenotypic characteristics of macrophages and dendritic cells (DCs) derived from monocytes. Monocytes were obtained from healthy young volunteers and cultured with ePF (n=12) or a control PF (cPF) (n=5) in the presence or absence of macrophage-colony stimulating factor (M-CSF) or IL-4 plus granulocyte macrophage-colony stimulating factor (GM-CSF). The ePF was demonstrated to increase expression levels of CD14 and CD64 on isolated monocytes in the presence or absence of M-CSF. Compared with cPF, addition of 10% ePF to GM-CSF plus IL-4-treated monocytes significantly down-regulated CD1a expression and up-regulated CD64 expression, but did not enhance expression levels of class II MHC. ePF had no effect, however, on tumor necrosis factor-alpha-induced maturation of DC. Levels of IL-6, IL-10 and M-CSF production were higher in ePF-treated than cPF-treated monocytes for both cell culture conditions with GM-CSF plus IL-4 and M-CSF. A neutralizing IL-6 antibody, but not an IL-10 antibody, abrogated the ePF-induced down-regulation of CD1a, up-regulation of CD64 and secretion of M-CSF. These results suggest that ePF favorably induces monocyte differentiation toward macrophages rather than DCs, and that this effect is mediated by IL-6. A reciprocal mode of cell differentiation between macrophages and DCs in response to ePF may be related to the pathogenesis of endometriosis.

The antigenic complex in HIT binds to B cells via complement and complement receptor 2 (CD21)

PubMed Central

Khandelwal, Sanjay; Lee, Grace M.; Hester, C. Garren; Poncz, Mortimer; McKenzie, Steven E.; Sachais, Bruce S.; Rauova, Lubica; Kelsoe, Garnett; Cines, Douglas B.; Frank, Michael

2016-01-01

Heparin-induced thrombocytopenia is a prothrombotic disorder caused by antibodies to platelet factor 4 (PF4)/heparin complexes. The mechanism that incites such prevalent anti-PF4/heparin antibody production in more than 50% of patients exposed to heparin in some clinical settings is poorly understood. To investigate early events associated with antigen exposure, we first examined the interaction of PF4/heparin complexes with cells circulating in whole blood. In healthy donors, PF4/heparin complexes bind preferentially to B cells (>90% of B cells bind to PF4/heparin in vitro) relative to neutrophils, monocytes, or T cells. Binding of PF4 to B cells is heparin dependent, and PF4/heparin complexes are found on circulating B cells from some, but not all, patients receiving heparin. Given the high proportion of B cells that bind PF4/heparin, we investigated complement as a mechanism for noncognate antigen recognition. Complement is activated by PF4/heparin complexes, co-localizes with antigen on B cells from healthy donors, and is present on antigen-positive B cells in patients receiving heparin. Binding of PF4/heparin complexes to B cells is mediated through the interaction between complement and complement receptor 2 (CR2 [CD21]). To the best of our knowledge, these are the first studies to demonstrate complement activation by PF4/heparin complexes, opsonization of PF4/heparin to B cells via CD21, and the presence of complement activation fragments on circulating B cells in some patients receiving heparin. Given the critical contribution of complement to humoral immunity, our observations provide new mechanistic insights into the immunogenicity of PF4/heparin complexes. PMID:27412887

The Malaria Parasite Cyclin H Homolog PfCyc1 Is Required for Efficient Cytokinesis in Blood-Stage Plasmodium falciparum.

PubMed

Robbins, Jonathan A; Absalon, Sabrina; Streva, Vincent A; Dvorin, Jeffrey D

2017-06-13

All well-studied eukaryotic cell cycles are driven by cyclins, which activate cyclin-dependent kinases (CDKs), and these protein kinase complexes are viable drug targets. The regulatory control of the Plasmodium falciparum cell division cycle remains poorly understood, and the roles of the various CDKs and cyclins remain unclear. The P. falciparum genome contains multiple CDKs, but surprisingly, it does not contain any sequence-identifiable G 1 -, S-, or M-phase cyclins. We demonstrate that P. falciparum Cyc1 (PfCyc1) complements a G 1 cyclin-depleted Saccharomyces cerevisiae strain and confirm that other identified malaria parasite cyclins do not complement this strain. PfCyc1, which has the highest sequence similarity to the conserved cyclin H, cannot complement a temperature-sensitive yeast cyclin H mutant. Coimmunoprecipitation of PfCyc1 from P. falciparum parasites identifies PfMAT1 and PfMRK as specific interaction partners and does not identify PfPK5 or other CDKs. We then generate an endogenous conditional allele of PfCyc1 in blood-stage P. falciparum using a destabilization domain (DD) approach and find that PfCyc1 is essential for blood-stage proliferation. PfCyc1 knockdown does not impede nuclear division, but it prevents proper cytokinesis. Thus, we demonstrate that PfCyc1 has a functional divergence from bioinformatic predictions, suggesting that the malaria parasite cell division cycle has evolved to use evolutionarily conserved proteins in functionally novel ways. IMPORTANCE Human infection by the eukaryotic parasite Plasmodium falciparum causes malaria. Most well-studied eukaryotic cell cycles are driven by cyclins, which activate cyclin-dependent kinases (CDKs) to promote essential cell division processes. Remarkably, there are no identifiable cyclins that are predicted to control the cell cycle in the malaria parasite genome. Thus, our knowledge regarding the basic mechanisms of the malaria parasite cell cycle remains unsatisfactory. We demonstrate that P. falciparum Cyc1 (PfCyc1), a transcriptional cyclin homolog, complements a cell cycle cyclin-deficient yeast strain but not a transcriptional cyclin-deficient strain. We show that PfCyc1 forms a complex in the parasite with PfMRK and the P. falciparum MAT1 homolog. PfCyc1 is essential and nonredundant in blood-stage P. falciparum PfCyc1 knockdown causes a stage-specific arrest after nuclear division, demonstrating morphologically aberrant cytokinesis. This work demonstrates a conserved PfCyc1/PfMAT1/PfMRK complex in malaria and suggests that it functions as a schizont stage-specific regulator of the P. falciparum life cycle. Copyright © 2017 Robbins et al.

Electrically heated particulate filter using catalyst striping

DOEpatents

Gonze, Eugene V; Paratore, Jr., Michael J; Ament, Frank

2013-07-16

An exhaust system that processes exhaust generated by an engine is provided. The system generally includes a particulate filter (PF) that filters particulates from the exhaust wherein an upstream end of the PF receives exhaust from the engine. A grid of electrically resistive material is applied to an exterior upstream surface of the PF and selectively heats exhaust passing through the grid to initiate combustion of particulates within the PF. A catalyst coating is applied to the PF that increases a temperature of the combustion of the particulates within the PF.

The characterization of obese polycystic ovary syndrome rat model suitable for exercise intervention.

PubMed

Wu, Chuyan; Lin, Feng; Qiu, Shuwei; Jiang, Zhongli

2014-01-01

To develop a new polycystic ovary syndrome (PCOS) rat model suitable for exercise intervention. Thirty six rats were randomly divided into three experimental groups: PCOS rats with high-fat diet (PF, n = 24), PCOS rats with ordinary diet (PO, n = 6), and control rats with ordinary diet (CO, n = 6). Two kinds of PCOS rat model were made by adjustment diet structure and testosterone injection for 28 days. After a successful animal model, PF model rats were randomly assigned to three groups: exercise with a continuation of high-fat diet (PF-EF, n = 6), sedentary with a continuation of high-fat diet (PF-SF, n = 6), exercise with an ordinary diet (PF-EO, n = 6). Fasting blood glucose (FBG) and insulin (FINS), estrogen (E2), progesterone (P), and testosterone (T) in serum were determined by RIA, and ovarian morphology was evaluated by Image-Pro plus 6.0. Body weight, Lee index, FINS increased significantly in PF rat model. Serum levels of E2 and T were significantly higher in PF and PO than in CO. Ovary organ index and ovarian areas were significant lower in PF than in CO. After intervention for 2 weeks, the levels of 1 h postprandial blood glucose (PBG1), 2 h postprandial blood glucose (PBG2), FINS and the serum levels of T decreased significantly in PF-EF rats and PF-EO rats. The ratio of FBG/FINS was significant higher in PF-EO rats than in PF-SF rats. Ovarian morphology showed that the numbers of preantral follicles and atretic follicles decreased significantly, and the numbers of antral follicles and corpora lutea increased significantly in the rats of PF-EF and PF-EO. By combination of high-fat diet and testosterone injection, the obese PCOS rat model is conformable with the lifestyle habits of fatty foods and insufficient exercise, and has metabolic and reproductive characteristics of human PCOS. This model can be applied to study exercise intervention.

Plasmodium falciparum chloroquine resistance transporter (PfCRT) isoforms PH1 and PH2 perturb vacuolar physiology.

PubMed

Callaghan, Paul S; Siriwardana, Amila; Hassett, Matthew R; Roepe, Paul D

2016-03-31

Recent work has perfected yeast-based methods for measuring drug transport by the Plasmodium falciparum chloroquine (CQ) resistance transporter (PfCRT). The approach relies on inducible heterologous expression of PfCRT in Saccharomyces cerevisiae yeast. In these experiments selecting drug concentrations are not toxic to the yeast, nor is expression of PfCRT alone toxic. Only when PfCRT is expressed in the presence of CQ is the growth of yeast impaired, due to inward transport of chloroquine (CQ) via the transporter. During analysis of all 53 known naturally occurring PfCRT isoforms, two isoforms (PH1 and PH2 PfCRT) were found to be intrinsically toxic to yeast, even in the absence of CQ. Additional analysis of six very recently identified PfCRT isoforms from Malaysia also showed some toxicity. In this paper the nature of this yeast toxicity is examined. Data also show that PH1 and PH2 isoforms of PfCRT transport CQ with an efficiency intermediate to that catalyzed by previously studied CQR conferring isoforms. Mutation of PfCRT at position 160 is found to perturb vacuolar physiology, suggesting a fitness cost to position 160 amino acid substitutions. These data further define the wide range of activities that exist for PfCRT isoforms found in P. falciparum isolates from around the globe.

Modification of the lipid moiety of the enterobacterial common antigen by the "Pseudomonas factor".

PubMed Central

Kuhn, H M; Neter, E; Mayer, H

1983-01-01

Pseudomonas aeruginosa produces a factor (PF) which affects the enterobacterial common antigen (ECA); resulting in failure of the antigen to modify erythrocytes for hemagglutination by ECA antibodies. In the present study the nature of PF was determined. Pronase treatment abolished its activity, indicating the protein nature of PF. PF-treated ECA no longer coated erythrocytes but still reacted with ECA antibodies in immunoelectrophoresis tests with monospecific antiserum to ECA, although differences were noted between the precipitation patterns of PF-treated and untreated ECA. Therefore, PF does not significantly affect the antigenic determinant of ECA but rather affects its lipid carrier, an L-glycerophosphatide. Accordingly, differences in the sugar chain could not be detected by high-voltage paper electrophoretic examinations of partial hydrolysates of PF-treated and untreated ECA. PF liberates all fatty acids from ECA, similarly to commercial lipases, as evidenced by the liberation of unsubstituted glycerol upon HF degradation at 0 degrees C of PF-treated ECA. The lipase activity of PF is indicated also by the observation that a strain of P. aeruginosa with reduced lipase production and an exolipase-negative strain affect ECA either less or not at all. We conclude that PF is a lipase acting on the lipid moiety of ECA, which is responsible for the coating of erythrocytes, but not significantly on the serological determinant, the amino sugar chain. Images PMID:6404831

PROMIS Physical Function Computer Adaptive Test Compared With Other Upper Extremity Outcome Measures in the Evaluation of Proximal Humerus Fractures in Patients Older Than 60 Years.

PubMed

Morgan, Jordan H; Kallen, Michael A; Okike, Kanu; Lee, Olivia C; Vrahas, Mark S

2015-06-01

To compare the PROMIS Physical Function Computer Adaptive Test (PROMIS PF CAT) to commonly used traditional PF measures for the evaluation of patients with proximal humerus fractures. Prospective. Two Level I trauma centers. Forty-seven patients older than 60 years with displaced proximal humerus fractures treated between 2006 and 2009. Evaluation included completion of the PROMIS PF CAT, the Constant Shoulder Score, the Disabilities of the Arm, Shoulder, and Hand (DASH) and the Short Musculoskeletal Functional Assessment (SMFA). Observed correlations among the administered PF outcome measures. On average, patients responded to 86 outcome-related items for this study: 4 for the PROMIS PF CAT (range: 4-8 items), 6 for the Constant Shoulder Score, 30 for the DASH, and 46 for the SMFA. Time to complete the PROMIS PF CAT (median completion time = 98 seconds) was significantly less than that for the DASH (median completion time = 336 seconds, P < 0.001) and for the SMFA (median completion time = 482 seconds, P < 0.001). PROMIS PF CAT scores correlated statistically significantly and were of moderate-to-high magnitude with all other PF outcome measure scores administered. This study suggests using the PROMIS PF CAT as a sole PF outcome measure can yield an assessment of upper extremity function similar to those provided by traditional PF measures, while substantially reducing patient assessment time.

Performance of Paracheck™-Pf, SD Bioline malaria Ag-Pf and SD Bioline malaria Ag-Pf/pan for diagnosis of falciparum malaria in the Central African Republic

PubMed Central

2014-01-01

Background Rapid diagnostic tests (RDTs) are the current complement to microscopy for ensuring prompt malaria treatment. We determined the performance of three candidate RDTs (Paracheck™-Pf, SD Bioline malaria Ag-Pf and SD Bioline malaria Ag-Pf/pan) for rapid diagnosis of malaria in the Central African Republic. Methods Blood samples from consecutive febrile patients who attended for laboratory analysis of malaria at the three main health centres of Bangui were screened by microscopy and the RDTs. Two reference standards were used to assess the performance of the RDTs: microscopy and, a combination of microscopy plus nested PCR for slides reported as negative, on the assumption that negative results by microscopy were due to sub-patent parasitaemia. Results We analysed 436 samples. Using the combined reference standard of microscopy + PCR, the sensitivity of Paracheck™-Pf was 85.7% (95% CI, 80.8–89.8%), that of SD Bioline Ag-Pf was 85.4% (95% CI, 80.5–90.7%), and that of SD Bioline Ag-Pf/pan was 88.2% (95% CI, 83.2–92.0%). The tests performed less well in cases of low parasitaemia; however, the sensitivity was > 95% at > 500 parasites/μl. Conclusions Overall, SD Bioline malaria Ag-Pf and SD Bioline malaria Ag-Pf/pan performed slightly better than Paracheck™-Pf. Use of RDTs with reinforced microscopy practice and laboratory quality assurance should improve malaria treatment in the Central African Republic. PMID:24568311

Imaging of plantar fascia disorders: findings on plain radiography, ultrasound and magnetic resonance imaging.

PubMed

Draghi, Ferdinando; Gitto, Salvatore; Bortolotto, Chandra; Draghi, Anna Guja; Ori Belometti, Gioia

2017-02-01

Plantar fascia (PF) disorders commonly cause heel pain and disability in the general population. Imaging is often required to confirm diagnosis. This review article aims to provide simple and systematic guidelines for imaging assessment of PF disease, focussing on key findings detectable on plain radiography, ultrasound and magnetic resonance imaging (MRI). Sonographic characteristics of plantar fasciitis include PF thickening, loss of fibrillar structure, perifascial collections, calcifications and hyperaemia on Doppler imaging. Thickening and signal changes in the PF as well as oedema of adjacent soft tissues and bone marrow can be assessed on MRI. Radiographic findings of plantar fasciitis include PF thickening, cortical irregularities and abnormalities in the fat pad located deep below the PF. Plantar fibromatosis appears as well-demarcated, nodular thickenings that are iso-hypoechoic on ultrasound and show low-signal intensity on MRI. PF tears present with partial or complete fibre interruption on both ultrasound and MRI. Imaging description of further PF disorders, including xanthoma, diabetic fascial disease, foreign-body reactions and plantar infections, is detailed in the main text. Ultrasound and MRI should be considered as first- and second-line modalities for assessment of PF disorders, respectively. Indirect findings of PF disease can be ruled out on plain radiography. Teaching Points • PF disorders commonly cause heel pain and disability in the general population.• Imaging is often required to confirm diagnosis or reveal concomitant injuries.• Ultrasound and MRI respectively represent the first- and second-line modalities for diagnosis.• Indirect findings of PF disease can be ruled out on plain radiography.

Differential mesocorticolimbic responses to palatable food in binge eating prone and binge eating resistant female rats.

PubMed

Sinclair, Elaine B; Culbert, Kristen M; Gradl, Dana R; Richardson, Kimberlei A; Klump, Kelly L; Sisk, Cheryl L

2015-12-01

Binge eating is a key symptom of many eating disorders (e.g. binge eating disorder, bulimia nervosa, anorexia nervosa binge/purge type), yet the neurobiological underpinnings of binge eating are poorly understood. The mesocorticolimbic reward circuit, including the nucleus accumbens and the medial prefrontal cortex, is likely involved because this circuit mediates the hedonic value and incentive salience of palatable foods (PF). Here we tested the hypothesis that higher propensity for binge eating is associated with a heightened response (i.e., Fos induction) of the nucleus accumbens and medial prefrontal cortex to PF, using an animal model that identifies binge eating prone (BEP) and binge eating resistant (BER) rats. Forty adult female Sprague-Dawley rats were given intermittent access to PF (high fat pellets) 3×/week for 3 weeks. Based on a pattern of either consistently high or consistently low PF consumption across these feeding tests, 8 rats met criteria for categorization as BEP, and 11 rats met criteria for categorization as BER. One week after the final feeding test, BEP and BER rats were either exposed to PF in their home cages or were given no PF in their home cages for 1h prior to perfusion, leading to three experimental groups for the Fos analysis: BEPs given PF, BERs given PF, and a No PF control group. The total number of Fos-immunoreactive (Fos-ir) cells in the nucleus accumbens core and shell, and the cingulate, prelimbic, and infralimbic regions of the medial prefrontal cortex was estimated by stereological analysis. PF induced higher Fos expression in the nucleus accumbens shell and core and in the prelimbic and infralimbic cortex of BEP rats compared to No PF controls. Throughout the nucleus accumbens and medial prefrontal cortex, PF induced higher Fos expression in BEP than in BER rats, even after adjusting for differences in PF intake. Differences in the neural activation pattern between BEP and BER rats were more robust in prefrontal cortex than in nucleus accumbens. These data confirm that PF activates brain regions responsible for encoding the incentive salience and hedonic properties of PF, and suggest that binge eating proneness is associated with enhanced responses to PF in brain regions that exert executive control over food reward. Copyright © 2015 Elsevier Inc. All rights reserved.

Differential mesocorticolimbic responses to palatable food in binge eating prone and binge eating resistant female rats

PubMed Central

Sinclair, Elaine B.; Culbert, Kristen M.; Gradl, Dana R.; Richardson, Kimberlei A.; Klump, Kelly L.; Sisk, Cheryl L.

2017-01-01

Binge eating is a key symptom of many eating disorders (e.g. binge eating disorder, bulimia nervosa, anorexia nervosa binge/purge type), yet the neurobiological underpinnings of binge eating are poorly understood. The mesocorticolimbic reward circuit, including the nucleus accumbens and the medial prefrontal cortex, is likely involved because this circuit mediates the hedonic value and incentive salience of palatable foods (PF). Here we tested the hypothesis that higher propensity for binge eating is associated with a heightened response (i.e., Fos induction) of the nucleus accumbens and medial prefrontal cortex to PF, using an animal model that identifies binge eating prone (BEP) and binge eating resistant (BER) rats. Forty adult female Sprague–Dawley rats were given intermittent access to PF (high fat pellets) 3×/week for 3 weeks. Based on a pattern of either consistently high or consistently low PF consumption across these feeding tests, 8 rats met criteria for categorization as BEP, and 11 rats met criteria for categorization as BER. One week after the final feeding test, BEP and BER rats were either exposed to PF in their home cages or were given no PF in their home cages for 1 h prior to perfusion, leading to three experimental groups for the Fos analysis: BEPs given PF, BERs given PF, and a No PF control group. The total number of Fos-immunoreactive (Fos-ir) cells in the nucleus accumbens core and shell, and the cingulate, prelimbic, and infralimbic regions of the medial prefrontal cortex was estimated by stereological analysis. PF induced higher Fos expression in the nucleus accumbens shell and core and in the prelimbic and infralimbic cortex of BEP rats compared to No PF controls. Throughout the nucleus accumbens and medial pre-frontal cortex, PF induced higher Fos expression in BEP than in BER rats, even after adjusting for differences in PF intake. Differences in the neural activation pattern between BEP and BER rats were more robust in prefrontal cortex than in nucleus accumbens. These data confirm that PF activates brain regions responsible for encoding the incentive salience and hedonic properties of PF, and suggest that binge eating proneness is associated with enhanced responses to PF in brain regions that exert executive control over food reward. PMID:26459117

Comparative study of flexural strength test methods on CAD/CAM Y-TZP dental ceramics

PubMed Central

Xu, Yongxiang; Han, Jianmin; Lin, Hong; An, Linan

2015-01-01

Clinically, fractures are the main cause of computer-aided design and computer-aided manufacturing (CAD/CAM) 3 mol%-yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) all-ceramic dental restorations failure because of repetitive occlusal loading. The goal of this work is to study the effect of test methods and specimen’s size on the flexural strength of five ceramic products. Both bi-axial flexure test (BI) and uni-axial flexure tests (UNI), including three-point flexure test (3PF) and four-point flexure test (4PF), are used in this study. For all five products, the flexural strength is as follows: BI > 3PF > 4PF. Furthermore, specimens with smaller size (3PF-s) have higher values than the bigger ones (3PF). The difference between BI and UNI resulted from the edge flaws in ceramic specimens. The relationship between different UNI (including 3PF-s, 3PF and 4PF) can be explained according to Weibull statistical fracture theory. BI is recommended to evaluate the flexural strength of CAD/CAM Y-TZP dental ceramics. PMID:26816646

Design Comparison of Inner and Outer Rotor of Permanent Magnet Flux Switching Machine for Electric Bicycle Application

NASA Astrophysics Data System (ADS)

Jusoh, L. I.; Sulaiman, E.; Bahrim, F. S.; Kumar, R.

2017-08-01

Recent advancements have led to the development of flux switching machines (FSMs) with flux sources within the stators. The advantage of being a single-piece machine with a robust rotor structure makes FSM an excellent choice for speed applications. There are three categories of FSM, namely, the permanent magnet (PM) FSM, the field excitation (FE) FSM, and the hybrid excitation (HE) FSM. The PMFSM and the FEFSM have their respective PM and field excitation coil (FEC) as their key flux sources. Meanwhile, as the name suggests, the HEFSM has a combination of PM and FECs as the flux sources. The PMFSM is a simple and cheap machine, and it has the ability to control variable flux, which would be suitable for an electric bicycle. Thus, this paper will present a design comparison between an inner rotor and an outer rotor for a single-phase permanent magnet flux switching machine with 8S-10P, designed specifically for an electric bicycle. The performance of this machine was validated using the 2D- FEA. As conclusion, the outer-rotor has much higher torque approximately at 54.2% of an innerrotor PMFSM. From the comprehensive analysis of both designs it can be conclude that output performance is lower than the SRM and IPMSM design machine. But, it shows that the possibility to increase the design performance by using “deterministic optimization method”.

A Weighted Measurement Fusion Particle Filter for Nonlinear Multisensory Systems Based on Gauss–Hermite Approximation

PubMed Central

Li, Yun

2017-01-01

We addressed the fusion estimation problem for nonlinear multisensory systems. Based on the Gauss–Hermite approximation and weighted least square criterion, an augmented high-dimension measurement from all sensors was compressed into a lower dimension. By combining the low-dimension measurement function with the particle filter (PF), a weighted measurement fusion PF (WMF-PF) is presented. The accuracy of WMF-PF appears good and has a lower computational cost when compared to centralized fusion PF (CF-PF). An example is given to show the effectiveness of the proposed algorithms. PMID:28956862

Clinical impact of culture-positive preservation fluid on solid organ transplantation: A systematic review and meta-analysis.

PubMed

Oriol, Isabel; Sabé, N; Tebé, C; Veroux, M; Boin, I F S F; Carratalà, J

2018-04-01

Contamination of the preservation fluid (PF) used for donated organs is a potential source of post-transplant infection. However, the information on this issue is scarce. We therefore conducted a systematic review and meta-analysis to assess the incidence of culture-positive PF and its impact on solid organ transplant (SOT) recipients. Seventeen studies were identified and included. The overall incidence of culture-positive PF was 37% (95% CI: 27% to 49%), and the incidence of PF-related infections among SOT recipients with PF cultures that grew pathogenic microorganisms was 10% (95% CI: 7% to 15%). There were differences in the rates of infections due to pathogenic microorganisms between SOT recipients who received pre-emptive treatment and those who did not, but without statistical significance. The mortality rate among SOT recipients with PF-related infection was 35% (95% CI: 21% to 53%). In conclusion, although contamination of the PF of donated organs is frequent, the incidence of PF-related infection is relatively low. A closely clinical and microbiologic monitoring of the SOT recipient in case of culture-positive PF, regardless of the type of microorganism isolated might be do in order to establish a prompt diagnosis of PF-related infection. Copyright © 2017 Elsevier Inc. All rights reserved.

Neural activation during imitation with or without performance feedback: An fMRI study.

PubMed

Zhang, Kaihua; Wang, Hui; Dong, Guangheng; Wang, Mengxing; Zhang, Jilei; Zhang, Hui; Meng, Weixia; Du, Xiaoxia

2016-08-26

In our daily lives, we often receive performance feedback (PF) during imitative learning, and we adjust our behaviors accordingly to improve performance. However, little is known regarding the neural mechanisms underlying this learning process. We hypothesized that appropriate PF would enhance neural activation or recruit additional brain areas during subsequent action imitation. Pictures of 20 different finger gestures without any social meaning were shown to participants from the first-person perspective. Imitation with or without PF was investigated by functional magnetic resonance imaging in 30 healthy subjects. The PF was given by a real person or by a computer. PF from a real person induced hyperactivation of the parietal lobe (precuneus and cuneus), cingulate cortex (posterior and anterior), temporal lobe (superior and transverse temporal gyri), and cerebellum (posterior and anterior lobes) during subsequent imitation. The positive PF and negative PF from a real person, induced the activation of more brain areas during the following imitation. The hyperactivation of the cerebellum, posterior cingulate cortex, precuneus, and cuneus suggests that the subjects exhibited enhanced motor control and visual attention during imitation after PF. Additionally, random PF from a computer had a small effect on the next imitation. We suggest that positive and accurate PF may be helpful for imitation learning. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Magnetic nanoparticles and thermally responsive polymer for targeted hyperthermia and sustained anti-cancer drug delivery.

PubMed

Wang, Sarah Y; Liu, Michelle C; Kang, Kyung A

2013-01-01

A novel cancer treatment method is being designed using a combination of iron oxide (Fe(3)O(4)) nanoparticles (IONPs) and Pluronic F-127 (PF127). IONPs have been used for heating tumors via an alternating electromagnetic (AEM) field. PF127 is a polymer possessing thermo-reversible and concentration-dependent gelation properties in aqueous solutions. PF127, as a gel, is an attractive drug delivery vehicle due to its zero-order drug release property. The combination of IONPs and PF127 would allow both short-term, tumor-specific, hyperthermic treatment, and long-term sustained drug delivery. As a preliminary study, the gelling and heating properties of IONPs/PF127 mixtures were investigated: 18% (w/w) PF127 was found to be ideal for our purpose because it gels at 28.0°C, i.e., it would be injectable at room temperature (20-25°C) and forms gel upon injection into the body (37°C). IONPs in PF127 showed little effect on gelation temperatures. The heating performance of IONPs in PF127 slightly, but linearly decreased with PF127. In the IONP concentration range of 0.01-0.05% (w/v) mixed with PF127 at 18% (w/w), the heating performance increased linearly with the increase in IONP concentration.

Biological strategy for the fabrication of highly ordered aragonite helices: the microstructure of the cavolinioidean gastropods

PubMed Central

Checa, Antonio G.; Macías-Sánchez, Elena; Ramírez-Rico, Joaquín

2016-01-01

The Cavolinioidea are planktonic gastropods which construct their shells with the so-called aragonitic helical fibrous microstructure, consisting of a highly ordered arrangement of helically coiled interlocking continuous crystalline aragonite fibres. Our study reveals that, despite the high and continuous degree of interlocking between fibres, every fibre has a differentiated organic-rich thin external band, which is never invaded by neighbouring fibres. In this way, fibres avoid extinction. These intra-fibre organic-rich bands appear on the growth surface of the shell as minuscule elevations, which have to be secreted differentially by the outer mantle cells. We propose that, as the shell thickens during mineralization, fibre secretion proceeds by a mechanism of contact recognition and displacement of the tips along circular trajectories by the cells of the outer mantle surface. Given the sizes of the tips, this mechanism has to operate at the subcellular level. Accordingly, the fabrication of the helical microstructure is under strict biological control. This mechanism of fibre-by-fibre fabrication by the mantle cells is unlike that any other shell microstructure. PMID:27181457

Active MHD Spectroscopy of Alfvén Eigenmodes on Alcator C-Mod

NASA Astrophysics Data System (ADS)

Sears, J.; Snipes, J.; Burke, W.; Parker, R.; Fasoli, A.

2004-11-01

Alfvén eigenmode resonances are excited in a variety of plasma conditions in C-Mod with two moderate-n antennas positioned above and below the outboard midplane. Power amplifiers (≈ 3 kW) sweep the driving frequency over the audio range (< 30 kHz) or over a selected ± 50 kHz range from 100 kHz to 1 MHz. Logic circuitry that calculates the center frequency of the Toroidal Alfven Eigenmode gap, f_TAE=v_A/4π qR, in real-time from BT and e measurements is being developed to enable the antennas to track f_TAE. Simultaneous in-vessel phase calibration of the pick-up coils will be used to better identify toroidal mode numbers. Shot-to-shot elongation scans do not show the dependence of damping on edge shear that was seen in results at JET. Inner wall limited plasmas with moderate outer gaps show higher damping rates than diverted plasmas with low outer gaps. Low frequency experiments below 20kHz will also be presented.

Processing and characterization of superconducting solenoids made of Bi-2212/Ag-alloy multifilament round wire for high field magnet applications

NASA Astrophysics Data System (ADS)

Chen, Peng

As the only high temperature superconductor with round wire (RW) geometry, Bi2Sr2CaCu2O8+x (Bi-2212) superconducting wire has the advantages of being multi-filamentary, macroscopically isotropic and twistable. With overpressure (OP) processing techniques recently developed by our group at the National High Magnetic Field Laboratory (NHMFL), the engineering current density (Je) of Bi-2212 RW can be dramatically increased. For example, Je of more than 600 A/mm 2 (4.2 K and 20 T) is achieved after 100 bar OP processing. With these intrinsically beneficial properties and recent processing progress, Bi-2212 RW has become very attractive for high field magnet applications, especially for nuclear magnetic resonance (NMR) magnets and accelerator magnets etc. This thesis summarizes my graduate study on Bi-2212 solenoids for high field and high homogeneity NMR magnet applications, which mainly includes performance study of Bi-2212 RW insulations, 1 bar and OP processing study of Bi-2212 solenoids, and development of superconducting joints between Bi-2212 RW conductors. Electrical insulation is one of the key components of Bi-2212 coils to provide sufficient electrical standoff within coil winding pack. A TiO 2/polymer insulation offered by nGimat LLC was systematically investigated by differential thermal analysis (DTA), thermo-gravimetric analysis (TGA), scanning electron microscopy (SEM), dielectric property measurements, and transport critical current (Ic) property measurements. About 29% of the insulation by weight is polymer. When the Bi-2212 wire is fully heat treated, this decomposes with slow heating to 400 °C in flowing O2. After the full reaction, we found that the TiO2 did not degrade the critical current properties, adhered well to the conductor, and provided a breakdown voltage of more than 100 V. A Bi-2212 RW wound solenoid coil was built using this insulation being offered by nGimat LLC. The coil resistance was constant through coil winding, polymer burn-off and full coil reaction. The coil was successfully tested at the NHMFL generating 33.8 T combined magnetic field in a 31.2 T background field. Multiple quenches occurred safely, which also illustrates that the insulation provided sufficient dielectric standoff. For Bi-2212 RW with a typical as-drawn diameter of 1.0-1.5 mm, this 15 microm thick insulation allows a very high coil packing factor of ~0.74, whereas earlier alumino-silicate braid insulation only allows packing factors of 0.38-0.48. In addition to the commercial TiO2/polymer insulation, we have also investigated sol-gel based ceramic coatings through collaboration with Harran University and another TiO2 based insulation coating at the NHMFL. Since Bi-2212 superconducting coils employ the Wind-and-React (W&R) technology, there are some potential issues in processing Bi-2212 coils, in particular for coils with a large thermal mass and dense oxide insulation coating. For this study, several Bi-2212 test solenoids with an outer diameter (OD) of about 90 mm were built and heat treated in 1 bar flowing oxygen with deadweights applied so as to simulate large coil packs. After the heat treatment (HT), coils were epoxy impregnated and cut. Winding pack was checked using SEM in terms of conductor geometry and insulation. Some samples were extracted to measure transport critical current Ic and critical temperature Tc. The results are very promising: test coils presented low creep behavior after standard partial melt HT under mechanical load, and no Ic degradation was found due to the application of mechanical load, and no inadequate oxygenation issue was seen for thick coils with ceramic coating on the wire. However, coils were partially electrically shorted after 1 bar HT under mechanical load, and we believe that increasing insulation coating thickness is necessary. In addition, several small solenoids were manufactured to study OP processing of Bi-2212 coils. The preliminary results indicate that there are some gaps between turns due to densification of wires (~4% wire diameter reduction) during 50-100 bar OP processing, and the diameter shrinking of conductors will potentially lead to coil sagging. So far, we have developed some methods to solve the issue of coil sagging, such as using flexible coil flange to allow smooth sagging of winding pack during OP processing. We have also investigated electrical joints between Bi-2212 RW conductors, which include resistive joints and superconducting joints. For resistive Bi-2212 joints, we evaluated conventional diffusion bonding method and soldering method. In general, the joints (with 42 mm joint length) resistances are below 200 nO at 4.2 K and magnetic fields up to 13.5 T, and the effect of magnetoresistance is clearly present. In addition to resistive joints, we successfully developed a superconducting joint between Bi-2212 RW conductors for persistent current mode (PCM) operations. (Abstract shortened by UMI.).

Comparing Universal Lynch Syndrome Tumor Screening Programs to Evaluate Associations Between Implementation Strategies and Patient Follow-through

PubMed Central

Cragun, Deborah; DeBate, Rita D.; Vadaparampil, Susan T.; Baldwin, Julie; Hampel, Heather; Pal, Tuya

2014-01-01

Purpose Universal tumor screening (UTS) for all colorectal cancer (CRC) patients can improve the identification of Lynch syndrome, the most common cause of hereditary CRC. This multiple-case study explored how variability in UTS procedures influence patient follow-through (PF) with germline testing after a screen-positive result. Methods Data were obtained through web-based surveys and telephone interviews with institutional informants. Institutions were categorized as Low-PF (≤10% underwent germline testing), Medium-PF (11–40%), or High-PF (>40%). To identify implementation procedures (i.e., conditions) unique High-PF institutions, qualitative comparative analysis was performed. Results Twenty-one informants from fifteen institutions completed surveys and/or interviews. Conditions present among all five High-PF institutions included: 1) disclosure of screen-positive results to patients by genetic counselors (GCs); and 2) GCs either facilitate physician referrals to genetics or eliminated the need for referrals. Although both of these High-PF conditions were present among two Medium-PF institutions, automatic reflex testing was lacking and difficulty contacting screen-positive patients was a barrier. The three remaining Medium-PF and five Low-PF institutions lacked High-PF conditions. Conclusion Methods for streamlining UTS procedures, incorporating a high level of involvement of GCs in results tracking and communication, and reducing barriers to patient contact are reviewed within a broader discussion on maximizing the effectiveness and public health impact of UTS. PMID:24651603

Deciphering the key residues in Plasmodium falciparum beta-ketoacyl acyl carrier protein reductase responsible for interactions with Plasmodium falciparum acyl carrier protein.

PubMed

Karmodiya, Krishanpal; Modak, Rahul; Sahoo, Nirakar; Sajad, Syed; Surolia, Namita

2008-10-01

The type II fatty acid synthase (FAS) pathway of Plasmodium falciparum is a validated unique target for developing novel antimalarials, due to its intrinsic differences from the typeI pathway operating in humans. beta-Ketoacyl acyl carrier protein (ACP) reductase (FabG) performs the NADPH-dependent reduction of beta-ketoacyl-ACP to beta-hydroxyacyl-ACP, the first reductive step in the elongation cycle of fatty acid biosynthesis. In this article, we report intensive studies on the direct interactions of Plasmodium FabG and Plasmodium ACP in solution, in the presence and absence of its cofactor, NADPH, by monitoring the change in intrinsic fluorescence of P.falciparum FabG (PfFabG) and by surface plasmon resonance. To address the issue of the importance of the residues involved in strong, specific and stoichiometric binding of PfFabG to P.falciparum ACP (PfACP), we mutated Arg187, Arg190 and Arg230 of PfFabG. The activities of the mutants were assessed using both an ACP-dependent and an ACP-independent assay. The affinities of all the PfFabG mutants for acetoacetyl-ACP (the physiological substrate) were reduced to different extents as compared to wild-type PfFabG, but were equally active in biochemical assays with the substrate analog acetoacetyl-CoA. Kinetic analysis and studies of direct binding between PfFabG and PfACP confirmed the identification of Arg187 and Arg230 as critical residues for the PfFabG-PfACP interactions. Our studies thus reveal the significance of the positively charged/hydrophobic patch located adjacent to the active site cavities of PfFabG for interactions with PfACP.

Advancing nutritional therapy: A novel polymeric formulation attenuates intestinal inflammation in a murine colitis model and suppresses pro-inflammatory cytokine production in ex-vivo cultured inflamed colonic biopsies.

PubMed

Alhagamhmad, Moftah H; Lemberg, Daniel A; Day, Andrew S; Tan, Li-Zsa; Ooi, Chee Y; Krishnan, Usha; Gupta, Nitin; Munday, John S; Leach, Steven T

2017-04-01

Nutritional therapy is a viable therapeutic option for the treatment of Crohn disease (CD). Therefore improving nutritional therapy would greatly benefit CD patients. The aim of this study was to define the anti-inflammatory properties of a novel nutritional polymeric formula (PF) in comparison to a currently available standard PF. Dextran sodium sulfate (DSS) was utilized to induce colitis in C57BL/6 mice with mice randomized to receive either standard PF or novel PF in addition to control groups. Changes in body weight were recorded and colonic damage was assessed histologically and biochemically. Additional experiments were also included where the cytokine response of colonic biopsies from pediatric CD patients was measured following exposure to standard PF or novel PF. DSS induced significant body weight loss, morphological changes in the colon, increased myeloperoxidase (MPO) activity and up-regulated colonic mRNA expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-12 and monocyte chemoattractant protein (MCP)-1, as well as associated histological changes. Other than histological damage, these inflammatory changes were reversed by both novel and standard PF. However, the novel PF, but not standard PF, completely suppressed TNF-α, IL-6 and IL-8 levels from cultured biopsies. Newly developed nutritional formula reproducibly ameliorated DSS-induced colitis in a murine model, although this response was not measurably different to standard PF. However, the novel PF was significantly superior in suppressing inflammatory cytokine release from cultured colonic biopsies. Collectively, these findings support a possible role for novel PF in advancing nutritional therapy for CD patients. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Deep brain stimulation of the center median-parafascicular complex of the thalamus has efficient anti-parkinsonian action associated with widespread cellular responses in the basal ganglia network in a rat model of Parkinson's disease.

PubMed

Jouve, Loréline; Salin, Pascal; Melon, Christophe; Kerkerian-Le Goff, Lydia

2010-07-21

The thalamic centromedian-parafascicular (CM/Pf) complex, mainly represented by Pf in rodents, is proposed as an interesting target for the neurosurgical treatment of movement disorders, including Parkinson's disease. In this study, we examined the functional impact of subchronic high-frequency stimulation (HFS) of Pf in the 6-hydroxydopamine-lesioned hemiparkinsonian rat model. Pf-HFS had significant anti-akinetic action, evidenced by alleviation of limb use asymmetry (cylinder test). Whereas this anti-akinetic action was moderate, Pf-HFS totally reversed lateralized neglect (corridor task), suggesting potent action on sensorimotor integration. At the cellular level, Pf-HFS partially reversed the dopamine denervation-induced increase in striatal preproenkephalin A mRNA levels, a marker of the neurons of the indirect pathway, without interfering with the markers of the direct pathway (preprotachykinin and preprodynorphin). Pf-HFS totally reversed the lesion-induced changes in the gene expression of cytochrome oxidase subunit I in the subthalamic nucleus, the globus pallidus, and the substantia nigra pars reticulata, and partially in the entopeduncular nucleus. Unlike HFS of the subthalamic nucleus, Pf-HFS did not induce per se dyskinesias and directly, although partially, alleviated L-3,4-dihydroxyphenylalanine (L-DOPA)-induced forelimb dyskinesia. Conversely, L-DOPA treatment negatively interfered with the anti-parkinsonian effect of Pf-HFS. Altogether, these data show that Pf-DBS, by recruiting a large basal ganglia circuitry, provides moderate to strong anti-parkinsonian benefits that might, however, be affected by L-DOPA. The widespread behavioral and cellular outcomes of Pf-HFS evidenced here demonstrate that CM/Pf is an important node for modulating the pathophysiological functioning of basal ganglia and related disorders.

Long-term clinical and radiographic outcome of patello-femoral realignment procedures: a minimum of 15-year follow-up.

PubMed

Vivod, Gregor; Verdonk, Peter; Drobnič, Matej

2014-11-01

A retrospective single-centre study was focused on the long-term outcome after different patello-femoral (PF) realignment procedures. Thirty-nine patients treated for recurrent PF instability were examined after a mean post-operative time of 22.5 years. Their 78 knees were divided into: non-operated knees (NON-OPERATED)-N = 24, isolated proximal procedures (PROXIMAL)-N = 22, isolated distal procedures (DISTAL)-N = 10, and combined procedures (COMBINED)-N = 22. PF-related medical history together with clinical, subjective (KOOS and Kujala scores), and radiographic (Caton-Deschamps PF height index, Kellgren-Lawrence scale for tibio-femoral OA, and Iwano classification for PF OA) evaluation was conducted. PF re-dislocation rate was comparable between PROXIMAL (36%), DISTAL (20%), and COMBINED (32%). Isolated proximal procedures revealed less central patella positions (PROXIMAL 64%; DISTAL 90%; COMBINED 95%) and more frequent PF apprehension test (PROXIMAL 82%; DISTAL 40%, COMBINED 50%). KOOS and Kujala scores were similar in all three surgical subgroups, but significantly lower than in NON-OPERATED. Patellas were positioned lower after DISTAL, 0.8 (0.5-1.0) or COMBINED, 0.9 (0.4-1.3). Kellgren-Lawrence scores ≥2 were found in 42% NON-OPERATED, 37% PROXIMAL, 70% DISTAL, and 59% COMBINED, whereas Iwano classification ≥2 was confirmed in 46% NON-OPERATED, 64% PROXIMAL, 80% DISTAL, and 86% COMBINED. High PF re-dislocation rates together with a very high incidence of PF OA indicate that PF realignment strategies used traditionally had failed to reach their long-term expectations. The transfer of tibial tuberosity resulted in more constrained PF joints than isolated proximal procedures which allowed for more residual PF instability. Distal procedures additionally increased the likelihood for tibio-femoral OA. III.

Platelet factor 4/CXCL4 induces phagocytosis and the generation of reactive oxygen metabolites in mononuclear phagocytes independently of Gi protein activation or intracellular calcium transients.

PubMed

Pervushina, Olga; Scheuerer, Barbara; Reiling, Norbert; Behnke, Lars; Schröder, Jens-M; Kasper, Brigitte; Brandt, Ernst; Bulfone-Paus, Silvia; Petersen, Frank

2004-08-01

Platelet factor 4 (PF-4), a platelet-derived CXC chemokine, is known to prevent human monocytes from apoptosis and to promote differentiation of these cells into HLA-DR(-) macrophages. In this study, we investigated the role of PF-4 in the control of acute monocyte proinflammatory responses involved in the direct combat of microbial invaders. We show that PF-4 increases monocyte phagocytosis and provokes a strong formation of oxygen radicals but lacks a chemotactic activity in these cells. Compared with FMLP, PF-4-induced oxidative burst was later in its onset but was remarkably longer in its duration (lasting for up to 60 min). Furthermore, in PF-4-prestimulated cells, FMLP- as well as RANTES-induced burst responses became synergistically enhanced. As we could show, PF-4-mediated oxidative burst in monocytes does not involve Gi proteins, elevation of intracellular free calcium concentrations, or binding to CXCR3B, a novel PF-4 receptor recently discovered on endothelial cells. Moreover, we found that PF-4 acts on macrophages in a dual manner. On the one hand, very similar to GM-CSF or M-CSF, PF-4 treatment of monocytes generates macrophages with a high capacity for unspecific phagocytosis. On the other hand, short term priming of GM-CSF-induced human macrophages with PF-4 substantially increases their capability for particle ingestion and oxidative burst. A comparable effect was also observed in murine bone marrow-derived macrophages, indicating cross-reactivity of human PF-4 between both species. Taken together, PF-4 may play a crucial role in the induction and maintenance of an unspecific immune response.

Physical Activity, Physical Fitness and Leukocyte Telomere Length: the Cardiovascular Health Study.

PubMed Central

Soares-Miranda, Luisa; Imamura, Fumiaki; Siscovick, David; Jenny, Nancy Swords; Fitzpatrick, Annette L; Mozaffarian, Dariush

2015-01-01

Introduction The influence of physical activity (PA) and physical fitness (PF) at older ages on changes in telomere length (TL), repetitive DNA sequences that may mark biologic aging, is not well-established. Few prior studies have been conducted in older adults, these were mainly cross-sectional, and few evaluated PF. Methods We investigated cross-sectional and prospective associations of PA and PF with leukocyte TL among 582 older adults (age 73±5 y at baseline) in the Cardiovascular Health Study, having serial TL measures and PA and PF assessed multiple times. Cross-sectional associations were assessed using multivariable repeated-measures regression, in which cumulatively averaged PA and PF measures were related to TL. Longitudinal analyses assessed cumulatively averaged PA and PF against later changes in TL; and changes in cumulatively averaged PA and PF against changes in TL. Results Cross-sectionally, greater walking distance and chair test performance, but not other PA and PF measures, were each associated with longer TL (p-trend=0.007, 0.04 respectively). In longitudinal analyses, no significant associations of baseline PA and PF with change in TL were observed. In contrast, changes in leisure-time activity and chair test performance were each inversely associated with changes in TL. Conclusions Cross-sectional analyses suggest that greater PA and PF are associated with longer TL. Prospective analyses show that changes in PA and PF are associated with differences in changes in TL. Even later in life, changes in certain PA and PF measures are associated with changes in TL, suggesting that leisure-time activity and fitness could reduce leukocyte telomere attrition among older adults. PMID:26083773

Bilateral comparison of 10 pF and 100 pF standards (ongoing BIPM key comparisons BIPM.EM-K14.a and 14.b) between the NIS (Egypt) and the BIPM

NASA Astrophysics Data System (ADS)

Gournay, Pierre; Helmy, M.; Raouf, A.; Hamed, Heba A. M.; Eliwa Gad, A.

2017-01-01

This report presents the results of a bilateral comparison of 10 pF and 100 pF capacitance standards between the NIS (Egypt) and the BIPM carried out in 2016. The comparison at 10 pF forms part of the ongoing BIPM key comparison BIPM.EM-K14.a and that at 100 pF of the ongoing BIPM key comparison BIPM.EM-K14.b. The BIPM is the pilot laboratory for both of these comparisons. Two 10 pF and 100 pF travelling standards belonging to the BIPM were used in this comparison carried out with an 'A-B-A' pattern of measurements. The standards were measured first at the BIPM for a period of about one month, then for a similar period at the NIS, and finally again at the BIPM. The measurand was the two terminal-pair capacitance at a frequency of either 1000 Hz or 1592 Hz, for a measuring rms voltage of 15 V at 10 pF and 10 V at 100 pF. One of the 10 pF travelling standards had to be eliminated from the comparison due to a bistable behaviour, possibly due to transportation. The results from the NIS and the BIPM at both 1000 Hz and 1592 Hz were found to be in good agreement, with a difference smaller than the relative expanded uncertainty (95 % confidence, k = 2) of about 0.72 × 10-6 at 10 pF and about 0.65 × 10-6 at 100 pF. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCEM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

DPF heater attachment mechanisms

DOEpatents

Gonze, Eugene V [Pinckney, MI; Ament, Frank [Troy, MI

2011-04-26

An exhaust filter system includes a particulate filter (PF) that is disposed downstream from an engine. The PF filters particulates within an exhaust from the engine. A heating element heats particulate matter in the PF. A fastener limits expansion movement of the heating element relative to the PF.

Subdural and intracerebral hemorrhage caused by spontaneous bleeding in the middle meningeal artery after coil embolization of a cerebral aneurysm.

PubMed

Kohyama, Shinya; Kakehi, Yoshiaki; Yamane, Fumitaka; Ooigawa, Hidetoshi; Kurita, Hiroki; Ishihara, Shoichiro

2014-10-01

Nontraumatic acute subdural hemorrhage (SDH) with intracerebral hemorrhage (ICH) is rare and is usually caused by severe bleeding from aneurysms or arteriovenous fistulas. We encountered a very rare case of spontaneous bleeding from the middle meningeal artery (MMA), which caused hemorrhage in the temporal lobe and subdural space 2 weeks after coil embolization of an ipsilateral, unruptured internal cerebral artery aneurysm in the cavernous portion. At onset, the distribution of hematoma on a computed tomography scan led us to believe that the treated intracavernous aneurysm could bleed into the intradural space. Emergency craniotomy revealed that the dura of the middle fossa was intact except for the point at the foramen spinosum where the exposed MMA was bleeding. Retrospectively, angiography just before and after embolization of the aneurysm did not show any aberrations in the MMA. Although the MMA usually courses on the outer surface of the dura and is unlikely to rupture without an external force, physicians should be aware that the MMA may bleed spontaneously and cause SDH and ICH. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Radial force on the vacuum chamber wall during thermal quench in tokamaks

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

Pustovitov, V. D., E-mail: pustovitov-vd@nrcki.ru

The radial force balance during a thermal quench in tokamaks is analyzed. As a rule, the duration τ{sub tp} of such events is much shorter than the resistive time τ{sub w} of the vacuum chamber wall. Therefore, the perturbations of the magnetic field B produced by the evolving plasma cannot penetrate the wall, which makes different the magnetic pressures on its inner and outer sides. The goal of this work is the analytical estimation of the resulting integral radial force on the wall. The plasma is considered axially symmetric; for the description of radial forces on the wall, the resultsmore » of V.D. Shafranov’s classical work [J. Nucl. Energy C 5, 251 (1963)] are used. Developed for tokamaks, the standard equilibrium theory considers three interacting systems: plasma, poloidal field coils, and toroidal field coils. Here, the wall is additionally incorporated with currents driven by ∂B/∂t≠0 accompanying the fast loss of the plasma thermal energy. It is shown that they essentially affect the force redistribution, thereby leading to large loads on the wall. The estimates prove that these loads have to be accounted for in the disruptive scenarios in large tokamaks.« less

Application of a Saddle-Type Eddy Current Sensor in Steel Ball Surface-Defect Inspection.

PubMed

Zhang, Huayu; Zhong, Mingming; Xie, Fengqin; Cao, Maoyong

2017-12-05

Steel ball surface-defect inspection was performed by using a new saddle-type eddy current sensor (SECS), which included a saddle coil and a signal conditioning circuit. The saddle coil was directly wound on the steel ball's outer bracket in a semi-circumferential direction. Driven by a friction wheel, the test steel ball rotated in a one-dimensional direction, such that the steel ball surface was fully scanned by the SECS. There were two purposes for using the SECS in the steel ball inspection system: one was to reduce the complexity of the unfolding wheel of the surface deployment mechanism, and the other was to reduce the difficulty of sensor processing and installation. Experiments were carried out on bearing steel balls in diameter of 8 mm with three types of representative and typical defects by using the SECS, and the results showed that the inspection system can detect surface defects as small as 0.05 mm in width and 0.1 mm in depth with high-repetition detection accuracy, and the detection efficiency of 5 pcs/s, which meet the requirement for inspecting ISO grade 10 bearing steel balls. The feasibility of detecting steel ball surface defects by SECS was verified.

Physics First: Impact on SAT Math Scores

NASA Astrophysics Data System (ADS)

Bouma, Craig E.

Improving science, technology, engineering, and mathematics (STEM) education has become a national priority and the call to modernize secondary science has been heard. A Physics First (PF) program with the curriculum sequence of physics, chemistry, and biology (PCB) driven by inquiry- and project-based learning offers a viable alternative to the traditional curricular sequence (BCP) and methods of teaching, but requires more empirical evidence. This study determined impact of a PF program (PF-PCB) on math achievement (SAT math scores) after the first two cohorts of students completed the PF-PCB program at Matteo Ricci High School (MRHS) and provided more quantitative data to inform the PF debate and advance secondary science education. Statistical analysis (ANCOVA) determined the influence of covariates and revealed that PF-PCB program had a significant (p < .05) impact on SAT math scores in the second cohort at MRHS. Statistically adjusted, the SAT math means for PF students were 21.4 points higher than their non-PF counterparts when controlling for prior math achievement (HSTP math), socioeconomic status (SES), and ethnicity/race.

Unique Cardiac Purkinje Fiber Transient Outward Current β-Subunit Composition

PubMed Central

Xiao, Ling; Koopmann, Tamara T.; Ördög, Balázs; Postema, Pieter G.; Verkerk, Arie O.; Iyer, Vivek; Sampson, Kevin J.; Boink, Gerard J.J.; Mamarbachi, Maya A.; Varro, Andras; Jordaens, Luc; Res, Jan; Kass, Robert S.; Wilde, Arthur A.; Bezzina, C.R.; Nattel, Stanley

2015-01-01

Rationale A chromosomal haplotype producing cardiac overexpression of dipeptidyl peptidase-like protein-6 (DPP6) causes familial idiopathic ventricular fibrillation. The molecular basis of transient outward current (Ito) in Purkinje fibers (PFs) is poorly understood. We hypothesized that DPP6 contributes to PF Ito and that its overexpression might specifically alter PF Ito properties and repolarization. Objective To assess the potential role of DPP6 in PF Ito. Methods and Results Clinical data in 5 idiopathic ventricular fibrillation patients suggested arrhythmia origin in the PF-conducting system. PF and ventricular muscle Ito had similar density, but PF Ito differed from ventricular muscle in having tetraethylammonium sensitivity and slower recovery. DPP6 overexpression significantly increased, whereas DPP6 knockdown reduced, Ito density and tetraethylammonium sensitivity in canine PF but not in ventricular muscle cells. The K+-channel interacting β-subunit K+-channel interacting protein type-2, essential for normal expression of Ito in ventricular muscle, was weakly expressed in human PFs, whereas DPP6 and frequenin (neuronal calcium sensor-1) were enriched. Heterologous expression of Kv4.3 in Chinese hamster ovary cells produced small Ito; Ito amplitude was greatly enhanced by coexpression with K+-channel interacting protein type-2 or DPP6. Coexpression of DPP6 with Kv4.3 and K+-channel interacting protein type-2 failed to alter Ito compared with Kv4.3/K+-channel interacting protein type-2 alone, but DPP6 expression with Kv4.3 and neuronal calcium sensor-1 (to mimic PF Ito composition) greatly enhanced Ito compared with Kv4.3/neuronal calcium sensor-1 and recapitulated characteristic PF kinetic/pharmacological properties. A mathematical model of cardiac PF action potentials showed that Ito enhancement can greatly accelerate PF repolarization. Conclusions These results point to a previously unknown central role of DPP6 in PF Ito, with DPP6 gain of function selectively enhancing PF current, and suggest that a DPP6-mediated PF early-repolarization syndrome might be a novel molecular paradigm for some forms of idiopathic ventricular fibrillation. PMID:23532596

The Characterization of Obese Polycystic Ovary Syndrome Rat Model Suitable for Exercise Intervention

PubMed Central

Qiu, Shuwei; Jiang, Zhongli

2014-01-01

Objective To develop a new polycystic ovary syndrome (PCOS) rat model suitable for exercise intervention. Method Thirty six rats were randomly divided into three experimental groups: PCOS rats with high-fat diet (PF, n = 24), PCOS rats with ordinary diet (PO, n = 6), and control rats with ordinary diet (CO, n = 6). Two kinds of PCOS rat model were made by adjustment diet structure and testosterone injection for 28 days. After a successful animal model, PF model rats were randomly assigned to three groups: exercise with a continuation of high-fat diet (PF-EF, n = 6), sedentary with a continuation of high-fat diet (PF-SF, n = 6), exercise with an ordinary diet (PF-EO, n = 6). Fasting blood glucose (FBG) and insulin (FINS), estrogen (E2), progesterone (P), and testosterone (T) in serum were determined by RIA, and ovarian morphology was evaluated by Image-Pro plus 6.0. Results Body weight, Lee index, FINS increased significantly in PF rat model. Serum levels of E2 and T were significantly higher in PF and PO than in CO. Ovary organ index and ovarian areas were significant lower in PF than in CO. After intervention for 2 weeks, the levels of 1 h postprandial blood glucose (PBG1), 2 h postprandial blood glucose (PBG2), FINS and the serum levels of T decreased significantly in PF-EF rats and PF-EO rats. The ratio of FBG/FINS was significant higher in PF-EO rats than in PF-SF rats. Ovarian morphology showed that the numbers of preantral follicles and atretic follicles decreased significantly, and the numbers of antral follicles and corpora lutea increased significantly in the rats of PF-EF and PF-EO. Conclusion By combination of high-fat diet and testosterone injection, the obese PCOS rat model is conformable with the lifestyle habits of fatty foods and insufficient exercise, and has metabolic and reproductive characteristics of human PCOS. This model can be applied to study exercise intervention. PMID:24905232

Goddard Space Flight Center Spacecraft Magnetic Test Facility Restoration Project

NASA Technical Reports Server (NTRS)

Vernier, Robert; Bonalksy, Todd; Slavin, James

2004-01-01

The Goddard Space Flight Center Spacecraft Magnetic Test Facility (SMTF) was constructed in the 1960's for the purpose of simulating geomagnetic and interplanetary magnetic field environments. The facility includes a three axis Braunbek coil system consisting of 12 loops, 4 loops on each of the three orthogonal axes; a remote Earth field sensing magnetometer and servo controller; and a remote power control and instrumentation building. The inner coils of the Braunbek system are 42-foot in diameter with a 10-foot by 10-foot opening through the outer coils to accommodate spacecraft access into the test volume. The physical size and precision of the facility are matched by only two other such facilities in the world. The facility was used extensively from the late 1960's until the early 1990's when the requirement for spacecraft level testing diminished. New NASA missions planned under the Living with a Star, Solar Terrestrial Probes, Explorer, and New Millennium Programs include precision, high-resolution magnetometers to obtain magnetic field data that is critical to fulfilling their scientific mission. It is highly likely that future Lunar and Martian exploration missions will also use precision magnetometers to conduct geophysical magnetic surveys. To ensure the success of these missions, ground-testing using a magnetic test facility such as the GSFC SMTF will be required. This paper describes the history of the facility, the future mission requirements that have renewed the need for spacecraft level magnetic testing, and the plans for restoring the facility to be capable of performing to its original design specifications.

Goddard Space Flight Center Spacecraft Magnetic Test Facility Restoration Project

NASA Technical Reports Server (NTRS)

Vernier, Robert; Bonalosky, Todd; Slavin, James

2004-01-01

The Goddard Space Flight Center Spacecraft Magnetic Test Facility (SMTF) was constructed in the 1960's for the purpose of simulating geomagnetic and interplanetary magnetic field environments. The facility includes a three axis Braunbek coil system consisting of 12 loops, 4 loops on each of the three orthogonal axes; a remote Earth field sensing magnetometer and servo controller; and a remote power control and instrumentation building. The inner coils of the Braunbek system are 42-foot in diameter with a 10-foot by 10-foot opening through the outer coils to accommodate spacecraft access into the test volume. The physical size and precision of the facility are matched by only two other such facilities in the world. The facility was used extensively from the late 1960's until the early 1990's when the requirement for spacecraft level testing diminished. New NASA missions planned under the Living with a Star, Solar Terrestrial Probes, Explorer, and New Millennium Programs include precision, high-resolution magnetometers to obtain magnetic field data that is critical to fulfilling their scientific mission. It is highly likely that future Lunar and Martian exploration missions will also use precision magnetometers to conduct geophysical magnetic surveys. To ensure the success of these missions, ground testing using a magnetic test facility such as the GSFC SMTF will be required. This paper describes the history of the facility, the future mission requirements that have renewed the need for spacecraft level magnetic testing, and the plans for restoring the facility to be capable of performing to its original design specifications.

Low levels of circulating platelet factor 4 (PF4, CXCL4) in subclinically hypothyroid autoimmune thyroiditis.

PubMed

Görar, S; Ademoğlu, E; Çarlıoğlu, A; Alioğlu, B; Bekdemir, H; Sağlam, B; Candan, Z; Üçler, R; Culha, C; Aral, Y

2016-02-01

Chemokines play an important role in the pathogenesis of autoimmune thyroid diseases. Platelet factor 4 (PF4, CXCL4) released from activated platelets is a chemokine. However, its clinical importance in autoimmune thyroiditis remains unknown. This study is intended to determine circulating levels of PF4 levels in patients with autoimmune thyroiditis (AIT). Circulating levels of PF4 were measured in 34 consecutive patients with newly diagnosed AIT and 18 euthyroid controls. Among AIT group, 16 patients were euthyroid and 18 had subclinic hypothyroidism. Controls and individuals with AIT were similar in terms of age. Serum levels of PF4 were comparable in patients with AIT and in controls. Among patients with AIT, PF4 was significantly lower in those with subclinical hypothyroidism than in euthyroid individuals (p = 0.001). In correlation analysis, PF4 was negatively correlated with TSH (r = -0.663, p = 0.000) and positively correlated with free T4 (r = 0.428, p = 0.012). There was not any significant correlation between PF4 and AbTPO, AbTg. The present study demonstrated for the first time that circulating PF4 levels are decreased in subclinically hypothyroid AIT. This result draws attention to the circulating PF4 levels in subclinically hypothyroid AIT and may shed light on further researches at this topic.

The Clp Chaperones and Proteases of the Human Malaria Parasite Plasmodium falciparum

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

M El Bakkouri; A Pow; A Mulichak

The Clpchaperones and proteases play an important role in protein homeostasis in the cell. They are highly conserved across prokaryotes and found also in the mitochondria of eukaryotes and the chloroplasts of plants. They function mainly in the disaggregation, unfolding and degradation of native as well as misfolded proteins. Here, we provide a comprehensive analysis of the Clpchaperones and proteases in the humanmalariaparasitePlasmodiumfalciparum. The parasite contains four Clp ATPases, which we term PfClpB1, PfClpB2, PfClpC and PfClpM. One PfClpP, the proteolytic subunit, and one PfClpR, which is an inactive version of the protease, were also identified. Expression of all Clpchaperonesmore » and proteases was confirmed in blood-stage parasites. The proteins were localized to the apicoplast, a non-photosynthetic organelle that accommodates several important metabolic pathways in P. falciparum, with the exception of PfClpB2 (also known as Hsp101), which was found in the parasitophorous vacuole. Both PfClpP and PfClpR form mostly homoheptameric rings as observed by size-exclusion chromatography, analytical ultracentrifugation and electron microscopy. The X-ray structure of PfClpP showed the protein as a compacted tetradecamer similar to that observed for Streptococcus pneumoniae and Mycobacterium tuberculosis ClpPs. Our data suggest the presence of a ClpCRP complex in the apicoplast of P. falciparum.« less

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

Park, Jeong Su; Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752; Kang, Dong Hoon

p70 ribosomal S6 kinase 1 (S6K1) is an important serine/threonine kinase and downstream target of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. PF-4708671 is a specific inhibitor of S6K1, and prevents S6K1-mediated phosphorylation of the S6 protein. PF-4708671 treatment often leads to apoptotic cell death. However, the protective mechanism against PF-4708671-induced cell death has not been elucidated. The nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway is essential for protecting cells against oxidative stress. p62, an adaptor protein in the autophagic process, enhances Nrf2 activation through the impairment of Keap1 activity. In thismore » study, we showed that PF-4708671 induces autophagic Keap1 degradation-mediated Nrf2 activation in p62-dependent manner. Furthermore, p62-dependent Nrf2 activation plays a crucial role in protecting cells from PF-4708671-mediated apoptosis. - Highlights: • PF-4708671, a S6K1-specific inhibitor, prevents S6K1-mediated S6 phosphorylation. • However, PF-4708671 treatment often leads to apoptotic cell death. • Protective mechanism against PF-4708671-induced cell death remains to be elucidated. • PF-4708671 induced p62-dependent, autophagic Keap1 degradation-mediated Nrf2 activation. • p62-dependent Nrf2 activation protects cells from PF-4708671-mediated apoptosis.« less

Determination of PF-04928473 in human plasma using liquid chromatography with tandem mass spectrometry

PubMed Central

Jain, Lokesh; Gardner, Erin R.; Venitz, Jürgen; Giaccone, Giuseppe; Houk, Brett E.; Figg, William D.

2010-01-01

A simple, rapid and sensitive liquid chromatography/tandem mass spectrometric (LC/MS/MS) analytical method was developed for quantification of Hsp90 inhibitor PF-04928473 in human plasma, following administration of its prodrug, PF-04929113. Sample processing involved protein precipitation by addition of 0.4 mL of methanol containing internal standard (PF-04972487) to 50 μL volume of plasma sample. Chromatographic separation of PF-04928473 and PF-04972487 was achieved on a Phenomenex® Luna C18(2) (2.0×50 mm, 5 μm) column using a gradient elution method with mobile phase solvents: methanol containing 0.1% formic acid and 0.1% formic acid at a flow rate of 0.25 mL/min. Detection was performed in electrospray positive ionization mode, monitoring the ion transitions from m/z 465.1→350.1 (PF-04928473) and m/z 447.0→329.1 (PF-04972487). The retention times for PF-04928473 and PF-04972487 were 1.86 and 2.85 minutes, respectively. Calibration curves were generated in the range of 2–2000 ng/mL. The accuracy and precision ranged from 94.1–99.0% and 86.7–97.6%, respectively, which were calculated using quality control samples of three different concentrations analyzed in quintuplicate on four different days. PMID:20951100

The mechanical and thermal characteristics of phenolic foam reinforced with kaolin powder and glass fiber fabric

NASA Astrophysics Data System (ADS)

Xiao, Wenya; Huang, Zhixiong; Ding, Jie

2017-12-01

In this work, kaolin powder and glass fiber fabric were added to PF in order to improve its thermal stability and mechanical property. Micro-structures of carbonized PF with kaolin powder were inspected by scanning electron microscopy (SEM) to demonstrate the filler’s pinning effect. SEM results illustrated modified PF had well morphology after high-temperature heat treatment. The Fourier transform infrared spectrometer (FTIR) test was carried out and found that kaolin powder only physically dispersed in PF. The compression test and thermal weight loss test were done on two groups of modified PF (Group A: add powder and fabric; Group B: add powder only). Results showed that all modified PF were better than pure PF, while foams with powder and fabric showed better mechanical characteristic and thermal stability compared with foams with powder only.

Beneficial influence of topical extra virgin olive oil application on an experimental model of penile fracture in rats.

PubMed

Gunes, Mustafa; Ozkol, Halil; Pirincci, Necip; Gecit, Ilhan; Bilici, Salim; Yildirim, Serkan

2015-08-01

Penile fracture (PF) is known as a traumatic rupture of the tunica albuginea of corpus cavernosum. In this study, we aimed to investigate the healing influence of topical extra virgin olive oil (EVOO) on PF through evaluating levels of some oxidative stress biomarkers for the first time. Histopathological evaluation was also realized. A total of 18 male Sprague-Dawley albino rats were divided into three groups of six rats each as control group, in PF (alone) group, and PF + EVOO group. Experimental PF was formed via incising from the proximal dorsal side of the penis in the rats of all groups except control. While in PF (alone) group, fracture was formed and the incision was primarily closed, in PF + EVOO group in addition to foregoing processes, EVOO was also administrated topically twice a day for 3 weeks. At the end of the experiment, all rats were killed and penectomy was carried out. While malondialdehyde, myeloperoxidase, lipid hyroperoxide, and total oxidant status significantly (p < 0.05) increased, reduced glutathione and total free sulfhydryl groups markedly (p < 0.05) decreased in PF (alone) group when compared with PF + EVOO group. Levels of these parameters were reversed to nearly normal values by topical EVOO application. Protection by EVOO is further substantiated via the improved histological findings in PF + EVOO group as against degenerative changes in the rats of PF (alone) group. Our data revealed that EVOO has protective effect in penile cavernosal tissue through probably its antioxidant, free radical defusing, anti-inflammatory, and antimicrobial effects. © The Author(s) 2013.

Pleural effusion levels of DJ-1 are increased in elderly lung cancer patients with malignant pleural effusions.

PubMed

Vavougios, George; Kerenidi, Theodora; Tsilioni, Irene; Zarogiannis, Sotirios G; Gourgoulianis, Konstantinos I

2015-01-01

DJ-1 is a multifunctional protein implicated in redox dependent cell fate decisions. The aim of our study was to determine the pleural fluid (PF) levels of DJ-1 in malignant pleural effusions (MPEs) secondary to lung cancer. Additionally, we opted to assess potential correlations of DJ-1 PF levels with the PF levels of superoxide dismutase-1 (SOD1) and 8-isoprostane that are known antioxidant enzymes and have been previously reported in MPEs. Forty lung cancer patients with cytological proof of MPE were enrolled in this study. The PF levels of DJ-1, SOD1, and 8-isoprostane were measured by means of enzyme-linked immunosorbent assay. The median PF levels of DJ-1 were 826 ng/mL (interquartile range, IQR: 482-1010 ng/mL). DJ-1 PF levels significantly correlated with PF Cu/Zn-SOD1 and PF 8-isoprostane levels (Spearman's rho, r; r = -0.476, P = 0.002 and r = -0.264, P = 0.033, respectively), PF lactate dehydrogenase (r = -0.497, P = 0.001) and total PF cell counts (r = -0.325, P = 0.041). Finally, in patients aged over 65 the PF DJ-1 levels were significantly higher than patients aged less than 65 (875 ng/mL vs. 607 ng/mL, respectively, P = 0.037). To our knowledge, this is the first report to determine DJ-1's levels in MPEs due to lung cancer. The negative correlations between DJ-1, SOD1, and 8-isorpostane warrant further investigation regarding the altered redox regulation associated with MPEs.

Electrically heated particulate filter regeneration using hydrocarbon adsorbents

DOEpatents

Gonze, Eugene V [Pinckney, MI; Ament, Frank [Troy, MI

2011-02-01

An exhaust system that processes exhaust generated by an engine is provided. The system generally includes a particulate filter (PF) that filters particulates from the exhaust wherein an upstream end of the PF receives exhaust from the engine. A grid of electrically resistive material selectively heats exhaust passing through the upstream end to initiate combustion of particulates within the PF. A hydrocarbon adsorbent coating applied to the PF releases hydrocarbons into the exhaust to increase a temperature of the combustion of the particulates within the PF.

Application of thermogravimetric studies for optimization of lithium hexafluorophosphate production

NASA Astrophysics Data System (ADS)

Smagin, A. A.; Matyukha, V. A.; Korobtsev, V. P.

Lithium hexafluorophosphate, isolated from hydrogen fluoride solution (anhydrous) by decanting and filtering, is an adduct of composition LiPF 6*HF. By thermogravimetric investigations the dynamics of HF removal from LiPF 6 by LiPF 6*HF thermal decomposition was studied. Based on the experimental data the constants entering into the equations as C = C0*exp( t*K0* exp(- E/RT)) were calculated, explaining the thermal decomposition processes of LiPF 6*HF and LiPF 6.

Study of soft X-ray emission during wire array implosion under plasma focus conditions at the PF-3 facility

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

Dan’ko, S. A.; Mitrofanov, K. N., E-mail: mitrofan@triniti.ru; Krauz, V. I.

2015-11-15

Results of measurements of soft X-ray emission with photon energies of <1 keV under conditions of a plasma focus (PF) experiment are presented. The experiments were carried out at the world’s largest PF device—the PF-3 Filippov-type facility (I ⩽ 3 MA, T/4 ≈ 15–20 µs, W{sub 0} ⩽ 3 MJ). X-ray emission from both a discharge in pure neon and with a tungsten wire array placed on the axis of the discharge chamber was detected. The wire array imploded under the action of the electric current intercepted from the plasma current sheath of the PF discharge in neon. The measuredmore » soft X-ray powers from a conventional PF discharge in gas and a PF discharge in the presence of a wire array were compared for the first time.« less

The 16PF Tradition in Contemporary Personality Assessment.

ERIC Educational Resources Information Center

Krug, Samuel E.

The 16 Personality Factor Questionnaire (16PF), which is reviewed historically in this essay, represents a unique and significant chapter in the history of personality assessment. During the first 20 years of its existence, the 16PF underwent numerous revisions and restandardizations. During that period, R. B. Cattell, the creator of the 16PF,…

A sugar phosphatase regulates the methylerythritol phosphate (MEP) pathway in malaria parasites

PubMed Central

Edwards, Rachel L.; Kelly, Megan L.; Hodge, Dana M.; Tolia, Niraj H.; Odom, Audrey R.

2014-01-01

Isoprenoid biosynthesis through the methylerythritol phosphate (MEP) pathway generates commercially important products and is a target for antimicrobial drug development. MEP pathway regulation is poorly understood in microorganisms. We employ a forward genetics approach to understand MEP pathway regulation in the malaria parasite, Plasmodium falciparum. The antimalarial fosmidomycin inhibits the MEP pathway enzyme deoxyxylulose 5-phosphate reductoisomerase (DXR). Fosmidomycin-resistant P. falciparum are enriched for changes in the PF3D7_1033400 locus (hereafter referred to as PfHAD1), encoding a homologue of haloacid dehalogenase (HAD)-like sugar phosphatases. We describe the structural basis for loss-of-function PfHAD1 alleles and find that PfHAD1 dephosphorylates a variety of sugar phosphates, including glycolytic intermediates. Loss of PfHAD1 is required for fosmidomycin resistance. Parasites lacking PfHAD1 have increased MEP pathway metabolites, particularly the DXR substrate, deoxyxylulose 5-phosphate. PfHAD1 therefore controls substrate availability to the MEP pathway. Because PfHAD1 has homologs in plants and bacteria, other HAD proteins may be MEP pathway regulators. PMID:25058848

Plasmodium falciparum erythrocyte membrane protein-1 specifically suppresses early production of host interferon-gamma.

PubMed

D'Ombrain, Marthe C; Voss, Till S; Maier, Alexander G; Pearce, J Andrew; Hansen, Diana S; Cowman, Alan F; Schofield, Louis

2007-08-16

Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP-1) is a variable antigen expressed by P. falciparum, the malarial parasite. PfEMP-1, present on the surface of infected host erythrocytes, mediates erythrocyte binding to vascular endothelium, enabling the parasite to avoid splenic clearance. In addition, PfEMP-1 is proposed to regulate host immune responses via interactions with the CD36 receptor on antigen-presenting cells. We investigated the immunoregulatory function of PfEMP-1 by comparing host cell responses to erythrocytes infected with either wild-type parasites or transgenic parasites lacking PfEMP-1. We showed that PfEMP-1 suppresses the production of the cytokine interferon-gamma by human peripheral blood mononuclear cells early after exposure to P. falciparum. Suppression of this rapid proinflammatory response was CD36 independent and specific to interferon-gamma production by gammadelta-T, NK, and alphabeta-T cells. These data demonstrate a parasite strategy for downregulating the proinflammatory interferon-gamma response and further establish transgenic parasites lacking PfEMP-1 as powerful tools for elucidating PfEMP-1 functions.

Investigation on Polylactide (PLA)/Poly(butylene adipate-co-terephthalate) (PBAT)/Bark Flour of Plane Tree (PF) Eco-Composites

PubMed Central

Dou, Qiang; Cai, Jun

2016-01-01

Polylactide (PLA)/poly(butylene adipate-co-terephthalate) (PBAT)/bark flour of plane tree (PF) eco-composites were prepared via melt blending. The morphologies, mechanical properties, crystal structures and melting and crystallization behaviors of the eco-composites were investigated by means of scanning electron microscopy (SEM), mechanical tests, polarized light microscopy (PLM), wide angle X-ray diffraction (WAXD) and differential scanning calorimetry (DSC), respectively. It is shown that the interfacial adhesion between PLA matrix and PF is weak and the mechanical properties of PLA/PF eco-composites are poor. The titanate treatment improves the adhesion between the matrix and the filler and enhances the stiffness of the eco-composites. The toughness is improved by PBAT and ductile fractured surfaces can be found. The spherulitic size of PLA is decreased by the addition of PF. The α crystalline form of PLA remains in the composites. Compared with PF, T-PF (PF treated by a titanate coupling agent) and PBAT have negative effects on the crystallization of PLA. PMID:28773515

Interaction of PF4 (CXCL4) with the vasculature: a role in atherosclerosis and angiogenesis.

PubMed

Aidoudi, Sallouha; Bikfalvi, Andreas

2010-11-01

Platelet factor-4 (PF4), a platelet-derived chemokine, has two important functions in the vasculature. It has a pro-atherogenic role while also having anti-angiogenic effects. The activity of platelet factor-4 (PF4), unlike other chemokines that bind to specific receptors, depends on its unusually high affinity for proteoglycans and other negatively charged molecules. High affinity for heparan sulfates was thought to be central to all of PF4's biological functions. However, other mechanisms have been described such as direct growth factor binding, activation of the CXCR3B chemokine receptor isoform that is present in some vascular cells or binding to lipoprotein-related protein-1 (LRP1). Furthermore, PF4 also binds to integrins with affinities similar to matrix molecules. These interactions may explain the effects of PF4 in healthy and pathological tissues. However, the mechanisms involved in PF4's activity are complex and may depend on a given tissue or localisation. Overall, while much is already known about PF4, its specific role in atherosclerosis and angiogenesis remains still to be clarified.

A homeodomain transcription factor gene, PfMSX, activates expression of Pif gene in the pearl oyster Pinctada fucata.

PubMed

Zhao, Mi; He, Maoxian; Huang, Xiande; Wang, Qi

2014-01-01

We reported pearl oyster Pinctada fucata cDNA and genomic characterization of a new homeobox-containing protein, PfMSX. The PfMSX gene encodes a transcription factor that was localized to the nucleus. Analyses of PfMSX mRNA in tissues and developmental stages showed high expressions in mantle or D-shaped larvae. In electrophoretic mobility shift assays (EMSAs) PfMSX binded to MSX consensus binding sites in the 5' flanking region of the Pif promoter. In co-transfection experiment PfMSX transactivated reporter constructs containing Pif promoter sequences, and mutation of the MSX-binding sites attenuated transactivation. A knockdown experiment using PfMSX dsRNA showed decreased Pif mRNA and unregular crystallization of the nacreous layer using scanning electron microscopy. Our results suggested that PfMSX was a conserved homeodomain transcription factor gene, which can activate Pif gene expression through MSX binding site, and was then involved in the mineralization process in pearl oyster Pinctada fucata. Our data provided important clues about mechanisms regulating biomineralization in pearl oyster.

Characterization and Structural Studies of the Plasmodium falciparum Ubiquitin and Nedd8 Hydrolase UCHL3

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

Artavanis-Tsakonas, Katerina; Weihofen, Wilhelm A.; Antos, John M.

Like their human hosts, Plasmodium falciparum parasites rely on the ubiquitin-proteasome system for survival. We previously identified PfUCHL3, a deubiquitinating enzyme, and here we characterize its activity and changes in active site architecture upon binding to ubiquitin. We find strong evidence that PfUCHL3 is essential to parasite survival. The crystal structures of both PfUCHL3 alone and in complex with the ubiquitin-based suicide substrate UbVME suggest a rather rigid active site crossover loop that likely plays a role in restricting the size of ubiquitin adduct substrates. Molecular dynamics simulations of the structures and a model of the PfUCHL3-PfNedd8 complex allowed themore » identification of shared key interactions of ubiquitin and PfNedd8 with PfUCHL3, explaining the dual specificity of this enzyme. Distinct differences observed in ubiquitin binding between PfUCHL3 and its human counterpart make it likely that the parasitic DUB can be selectively targeted while leaving the human enzyme unaffected.« less

A Homeodomain Transcription Factor Gene, PfMSX, Activates Expression of Pif Gene in the Pearl Oyster Pinctada fucata

PubMed Central

Zhao, Mi; He, Maoxian; Huang, Xiande; Wang, Qi

2014-01-01

We reported pearl oyster Pinctada fucata cDNA and genomic characterization of a new homeobox-containing protein, PfMSX. The PfMSX gene encodes a transcription factor that was localized to the nucleus. Analyses of PfMSX mRNA in tissues and developmental stages showed high expressions in mantle or D-shaped larvae. In electrophoretic mobility shift assays (EMSAs) PfMSX binded to MSX consensus binding sites in the 5′ flanking region of the Pif promoter. In co-transfection experiment PfMSX transactivated reporter constructs containing Pif promoter sequences, and mutation of the MSX-binding sites attenuated transactivation. A knockdown experiment using PfMSX dsRNA showed decreased Pif mRNA and unregular crystallization of the nacreous layer using scanning electron microscopy. Our results suggested that PfMSX was a conserved homeodomain transcription factor gene, which can activate Pif gene expression through MSX binding site, and was then involved in the mineralization process in pearl oyster Pinctada fucata. Our data provided important clues about mechanisms regulating biomineralization in pearl oyster. PMID:25099698

Iron stores of breastfed infants during the first year of life.

PubMed

Ziegler, Ekhard E; Nelson, Steven E; Jeter, Janice M

2014-05-21

The birth iron endowment provides iron for growth in the first months of life. We describe the iron endowment under conditions of low dietary iron supply. Subjects were infants participating in a trial of Vitamin D supplementation from 1 to 9 months. Infants were exclusively breastfed at enrollment but could receive complementary foods from 4 months but not formula. Plasma ferritin (PF) and transferrin receptor (TfR) were determined at 1, 2, 4, 5.5, 7.5, 9 and 12 months. At 1 month PF ranged from 38 to 752 µg/L and was only weakly related to maternal PF. PF declined subsequently and flattened out at 5.5 months. PF of females was significantly higher than PF of males except at 12 months. TfR increased with age and was inversely correlated with PF. PF and TfR tracked strongly until 9 months. Iron deficiency (PF < 10 µg/L) began to appear at 4 months and increased in frequency until 9 months. Infants with ID were born with low iron endowment. We concluded that the birth iron endowment is highly variable in size and a small endowment places infants at risk of iron deficiency before 6 months. Boys have smaller iron endowments and are at greater risk of iron deficiency than girls.

Photoaffinity Labeling of the Plasmodium falciparum Chloroquine Resistance Transporter with a Novel Perfluorophenylazido Chloroquine†

PubMed Central

Lekostaj, Jacqueline K.; Natarajan, Jayakumar K.; Paguio, Michelle F.; Wolf, Christian; Roepe, Paul D.

2009-01-01

Several models describing how amino acid substitutions in the Plasmodium falciparum chloroquine resistance transporter (PfCRT) confer resistance to chloroquine (CQ) and other antimalarial drugs have been proposed. Further progress requires molecular analysis of interactions between purified reconstituted PfCRT protein and these drugs. We have thus designed and synthesized several perfluorophenyl azido (pfpa) CQ analogues for PfCRT photolabeling studies. One particularly useful probe (AzBCQ) places the pfpa group at the terminal aliphatic N of CQ via a flexible four-carbon ester linker and includes a convenient biotin tag. This probe photolabels PfCRT in situ with high specificity. Using reconstituted proteoliposomes harboring partially purified recombinant PfCRT, we analyze AzBCQ photolabeling versus competition with CQ and other drugs to probe the nature of the CQ binding site. We also inspect how pH, the chemoreversal agent verapamil (VPL), and various amino acid mutations in PfCRT that cause CQ resistance (CQR) affect the efficiency of AzBCQ photolabeling. Upon gel isolation of AzBCQ-labeled PfCRT followed by trypsin digestion and mass spectrometry analysis, we are able to define a single AzBCQ covalent attachment site lying within the digestive vacuolar-disposed loop between putative helices 9 and 10 of PfCRT. Taken together, the data provide important new insight into PfCRT function and, along with previous results, allow us to propose a model for a single CQ binding site in the PfCRT protein. PMID:18767816

Photoaffinity labeling of the Plasmodium falciparum chloroquine resistance transporter with a novel perfluorophenylazido chloroquine.

PubMed

Lekostaj, Jacqueline K; Natarajan, Jayakumar K; Paguio, Michelle F; Wolf, Christian; Roepe, Paul D

2008-09-30

Several models describing how amino acid substitutions in the Plasmodium falciparum chloroquine resistance transporter (PfCRT) confer resistance to chloroquine (CQ) and other antimalarial drugs have been proposed. Further progress requires molecular analysis of interactions between purified reconstituted PfCRT protein and these drugs. We have thus designed and synthesized several perfluorophenyl azido (pfpa) CQ analogues for PfCRT photolabeling studies. One particularly useful probe (AzBCQ) places the pfpa group at the terminal aliphatic N of CQ via a flexible four-carbon ester linker and includes a convenient biotin tag. This probe photolabels PfCRT in situ with high specificity. Using reconstituted proteoliposomes harboring partially purified recombinant PfCRT, we analyze AzBCQ photolabeling versus competition with CQ and other drugs to probe the nature of the CQ binding site. We also inspect how pH, the chemoreversal agent verapamil (VPL), and various amino acid mutations in PfCRT that cause CQ resistance (CQR) affect the efficiency of AzBCQ photolabeling. Upon gel isolation of AzBCQ-labeled PfCRT followed by trypsin digestion and mass spectrometry analysis, we are able to define a single AzBCQ covalent attachment site lying within the digestive vacuolar-disposed loop between putative helices 9 and 10 of PfCRT. Taken together, the data provide important new insight into PfCRT function and, along with previous results, allow us to propose a model for a single CQ binding site in the PfCRT protein.

The Clp Chaperones and Proteases of the Human Malaria Parasite Plasmodium falciparum

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

Bakkouri, Majida El; Pow, Andre; Mulichak, Anne

The Clp chaperones and proteases play an important role in protein homeostasis in the cell. They are highly conserved across prokaryotes and found also in the mitochondria of eukaryotes and the chloroplasts of plants. They function mainly in the disaggregation, unfolding and degradation of native as well as misfolded proteins. Here, we provide a comprehensive analysis of the Clp chaperones and proteases in the human malaria parasite Plasmodium falciparum. The parasite contains four Clp ATPases, which we term PfClpB1, PfClpB2, PfClpC and PfClpM. One PfClpP, the proteolytic subunit, and one PfClpR, which is an inactive version of the protease, weremore » also identified. Expression of all Clp chaperones and proteases was confirmed in blood-stage parasites. The proteins were localized to the apicoplast, a non-photosynthetic organelle that accommodates several important metabolic pathways in P. falciparum, with the exception of PfClpB2 (also known as Hsp101), which was found in the parasitophorous vacuole. Both PfClpP and PfClpR form mostly homoheptameric rings as observed by size-exclusion chromatography, analytical ultracentrifugation and electron microscopy. The X-ray structure of PfClpP showed the protein as a compacted tetradecamer similar to that observed for Streptococcus pneumoniae and Mycobacterium tuberculosis ClpPs. Our data suggest the presence of a ClpCRP complex in the apicoplast of P. falciparum.« less

Nematicidal protease genes screened from a soil metagenomic library to control Radopholus similis mediated by Pseudomonas fluorescens pf36.

PubMed

Chen, Deqiang; Wang, Dongwei; Xu, Chunling; Chen, Chun; Li, Junyi; Wu, Wenjia; Huang, Xin; Xie, Hui

2018-04-01

Controlling Radopholus similis, an important phytopathogenic nematode, is a challenge worldwide. Herein, we constructed a metagenomic fosmid library from the rhizosphere soil of banana plants, and six clones with protease activity were obtained by functionally screening the library. Furthermore, subclones were constructed using the six clones, and three protease genes with nematicidal activity were identified: pase1, pase4, and pase6. The pase4 gene was successfully cloned and expressed, demonstrating that the protease PASE4 could effectively degrade R. similis tissues and result in nematode death. Additionally, we isolated a predominant R. similis-associated bacterium, Pseudomonas fluorescens (pf36), from 10 R. similis populations with different hosts. The pase4 gene was successfully introduced into the pf36 strain by vector transformation and conjugative transposition, and two genetically modified strains were obtained: p4MCS-pf36 and p4Tn5-pf36. p4MCS-pf36 had significantly higher protease expression and nematicidal activity (p < 0.05) than p4Tn5-pf36 in a microtiter plate assay, whereas p4Tn5-pf36 was superior to p4MCS-pf36 in terms of genetic stability and controlling R. similis in growth pot tests. This study confirmed that R. similis is inhibited by the associated bacterium pf36-mediated expression of nematicidal proteases. Herein, a novel approach is provided for the study and development of efficient, environmentally friendly, and sustainable biocontrol techniques against phytonematodes.

Triazole-functionalized N-heterocyclic carbene complexes of palladium and platinum and efficient aqueous Suzuki-Miyaura coupling reaction.

PubMed

Gu, Shaojin; Xu, Hui; Zhang, Na; Chen, Wanzhi

2010-07-05

Imidazolium salts bearing triazole groups are synthesized via a copper catalyzed click reaction, and the silver, palladium, and platinum complexes of their N-heterocyclic carbenes are studied. [Ag(4)(L1)(4)](PF(6))(4), [Pd(L1)Cl](PF(6)), [Pt(L1)Cl](PF(6)) (L1=3-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-1-(pyrimidin-2-yl)-1H-imidazolylidene), [Pd(2)(L2)(2)Cl(2)](PF(6))(2), and [Pd(L2)(2)](PF(6))(2) (L2=1-butyl-3-((1-(pyridin-2-yl)-1H-1,2,3-triazol-4-yl)methyl)imidazolylidene) have been synthesized and fully characterized by NMR, elemental analysis, and X-ray crystallography. The silver complex [Ag(4)(L1)(4)](PF(6))(4) consists of a Ag(4) zigzag chain. The complexes [Pd(L1)Cl](PF(6)) and [Pt(L1)Cl](PF(6)), containing a nonsymmetrical NCN' pincer ligand, are square planar with a chloride trans to the carbene donor. [Pd(2)(L2)(2)Cl(2)](PF(6))(2) consists of two palladium centers with CN(2)Cl coordination mode, whereas the palladium in [Pd(L2)(2)](PF(6))(2) is surrounded by two carbene and two triazole groups with two uncoordinated pyridines. The palladium compounds are highly active for Suzuki-Miyaura cross coupling reactions of aryl bromides and 1,1-dibromo-1-alkenes in neat water under an air atmosphere.

Immune complexes formed following the binding of anti-platelet factor 4 (CXCL4) antibodies to CXCL4 stimulate human neutrophil activation and cell adhesion.

PubMed

Xiao, Zhihua; Visentin, Gian P; Dayananda, Kannayakanahalli M; Neelamegham, Sriram

2008-08-15

We tested the possibility that immune complexes formed following platelet factor 4 (PF4/CXCL4) binding to anti-PF4 antibody can stimulate neutrophil activation, similar to previous reports with platelets. Monoclonal Abs against PF4 and IgG from a heparin-induced thrombocytopenia (HIT) patient were applied. We observed that although PF4 or anti-PF4 antibody alone did not alter neutrophil function, costimulation with both reagents resulted in approximately 3-fold increase in cell surface Mac-1 expression, enhanced cell adhesion via L-selectin and CD18 integrins, and degranulation of secondary and tertiary granules. The level of Mac-1 up-regulation peaked at an intermediate PF4 dose, suggesting that functional response varies with antigen-antibody stoichiometry. PF4 binding to neutrophils was blocked by chondroitinase ABC. Cell activation was inhibited by both chondroitinase ABC and anti-CD32/FcgammaRII blocking mAb, IV.3. Confocal microscopy demonstrated that immune complexes colocalize with CD32a. Studies with HIT IgG demonstrated that neutrophils could be activated in the absence of exogenous heparin. These data, together, show that leukocyte surface chondroitin sulfates promote neutrophil activation by enhancing immune-complex binding to CD32a. Studies with recombinant PF4 suggest a role for arginine 49 in stabilizing PF4-chondroitin binding. Neutrophils activated via this mechanism may contribute to thrombosis and inflammation in patients mounting an immune response to PF4-heparin.

Paeoniflorin, a Monoterpene Glycoside, Protects the Brain from Cerebral Ischemic Injury via Inhibition of Apoptosis.

PubMed

Zhang, Yuqin; Li, Huang; Huang, Mingqing; Huang, Mei; Chu, Kedan; Xu, Wei; Zhang, Shengnan; Que, Jinhua; Chen, Lidian

2015-01-01

Paeoniflorin (PF) is a principal bioactive component, which exhibits many pharmacological effects, including protection against ischemic injury. This paper aimed to investigate the protective effect of PF both in vivo and in vitro. Middle cerebral artery occlusion (MCAO) was performed on male Sprague-Dawley (SD) rat for 2 h, and different doses of PF or vehicle were administered 2 h after reperfusion. Rats were sacrificed after 7 days treatment of PF/vehicle. PF treatment for 7 days ameliorated MCAO-induced neurological deficit and decreased the infarct area. Further study demonstrated that PF inhibited the over-activation of astrocytes and apoptosis of neurons, and PF promoted up-regulation of neuronal specific marker neuron-specific nuclear (NeuN) and microtubule-associated protein 2 (MAP-2) in brain. Moreover, NMDA-induced neuron apoptosis was employed. The in vitro study revealed that PF treatment protected against NMDA-induced cell apoptosis and neuronal loss via up-regulation of neuronal specific marker NeuN, MAP-2 and Bcl-2 and the down-regulation Bax. Taken together, the present study demonstrates that PF produces its protective effect by inhibiting the over-activation of astrocytes, apoptosis of neurons and up-regulation of neuronal specific marker NeuN, MAP-2, and B-cell lymphoma-2 (Bcl-2), and down-regulation Bax. Our study reveals that PF may be a potential neuroprotective agent for stroke and can provide basic data for clinical use.

Investigation of a Potential Protective Mechanism Against Heparin-Induced Thrombocytopenia in Patients on Chronic Intermittent Hemodialysis

PubMed Central

Tanhehco, Yvette C.; Cuker, Adam; Rudnick, Michael; Sachais, Bruce S.

2015-01-01

BACKGROUND Heparin-induced thrombocytopenia (HIT) develops as a result of platelet (PLT) activation by anti-platelet factor 4 (PF4)/heparin complex antibodies. Despite repeated exposure to heparin, patients undergoing chronic intermittent hemodialysis (HD) rarely develop HIT. We investigated the possibility that HD decreases/removes PF4 from PLT surfaces and/or plasma, thereby disfavoring immune complex formation as a mechanism of protection against HIT. MATERIALS AND METHODS We enrolled 20 patients undergoing chronic HD at the Penn Presbyterian Medical Center. Blood samples were drawn before, during and after treatment in the presence and absence of heparin. PF4, PF4/heparin antibody, heparin, and P-selectin levels were measured. RESULTS No patients demonstrated clinical symptoms of HIT. PLT surface PF4 levels decreased and plasma PF4 levels increased concurrently with increase in plasma heparin concentration. In the absence of heparin, PLT surface and plasma PF4 levels were unchanged. Anti-PF4/heparin antibodies, which were non-functional by the serotonin release assay, were detectable in 8 patients. PLT surface P-selectin levels did not change during treatment. CONCLUSIONS Removal of PLT surface and/or plasma PF4 as a mechanism of protection against HIT in patients undergoing HD is not supported by the results of our study, although the transient decrease in PLT surface PF4 in the presence of large amounts of heparin remains a candidate mechanism. The small sample size, single type of dialyzer membrane, and early sampling time points may have led to the inability to detect changes in PF4 levels. Future studies should explore other potential protective mechanisms. PMID:23305841

The influence of transection site on the development of pancreatic fistula in patients undergoing distal pancreatectomy: A review of 294 consecutive cases.

PubMed

Sell, Naomi M; Pucci, Michael J; Gabale, Salil; Leiby, Benjamin E; Rosato, Ernest L; Winter, Jordan M; Yeo, Charles J; Lavu, Harish

2015-06-01

Pancreatic fistula (PF) is a significant cause of morbidity in patients undergoing distal pancreatectomy (DP), with an incidence of 15-40%. It remains unclear if the location of pancreatic transection affects the rate of PF occurrence. This study examines the correlation between the transection site of the pancreas during DP and the incidence of PF. All cases of DP from October 2005 to January 2012 were reviewed retrospectively from an institutional review board-approved database at the Thomas Jefferson University Hospital. Patient demographics and perioperative outcomes were analyzed. The pancreatic transection location was determined by review of operative reports, and then dichotomized into 2 groups: neck/body or tail. PF were graded following the International Study Group on Pancreatic Fistula guidelines. During the study period, 294 DP were performed with 244 pancreas transections at the neck/body and 50 at the tail. Of the 294 patients, 52 (17.7%) developed a postoperative PF. The incidence of PF after transection at the tail of the pancreas was higher (28%) when compared with transection at the neck/body (15.6%; P = .04). When stratified by PF grade, grade A PF occurred more commonly when transection of the gland was at the tail (22% tail vs 8.2% neck/body; P = .007); however, no difference was found for grade B/C PF (6% tail vs 7.4% neck/body; P = 1). Our data suggest that PF occurs more often when the tail is transected during DP, although the majority are low grade and of minimal clinical significance. More severe PF occurred equally between the transection sites. Copyright © 2015 Elsevier Inc. All rights reserved.

Metabolic programming effects initiated in the suckling period predisposing for adult-onset obesity cannot be reversed by calorie restriction.

PubMed

Srinivasan, Malathi; Mahmood, Saleh; Patel, Mulchand S

2013-03-01

Neonatal rats reared on high-carbohydrate (HC) milk formula developed chronic hyperinsulinemia and adult-onset obesity due to programming of islets and the hypothalamic energy circuitry. In this study, calorie restriction by pair-feeding was imposed on HC male rats (HC/PF) to normalize food intake similar to that of mother-fed (MF) rats from weaning until postnatal day 140. A group of HC/PF rats was switched over to ad libitum feeding (HC/PF/AL) from days 90 to 140. Pair-feeding reduced body weight gains and serum insulin and leptin levels in HC/PF rats compared with HC rats, but these parameters were restored to HC levels in the HC/PF/AL rats after ad libitum feeding. Interestingly, the heightened insulin secretory response of isolated islets from adult HC/PF and HC/PF/ AL rats to glucose, acetylcholine, and oxymetazoline were not significantly different from the responses of islets from HC rats. Similarly, the expression of neuropeptide Y and proopiomelanocortin in the hypothalamus was not significantly different among HC, HC/PF, and HC/PF/AL rats. Expression of the leptin receptor in the hypothalami from the HC, HC/PF, and HC/PF/AL rats mirrored that of serum leptin, whereas suppressor of cytokine signaling 3 (Socs3) expression remained high in these three groups. The results indicate that, although calorie restriction resulted in reduction in body weight gain and normalized the serum hormonal pattern, the programed predisposition for the hypersecretory capacity of islets and the hypothalamic hyperphagic response in the HC rats could not be permanently overcome by the pair-feeding imposed on HC rats.

Effects of peritoneal fluid from endometriosis patients on interferon-gamma-induced protein-10 (CXCL10) and interleukin-8 (CXCL8) released by neutrophils and CD4+ T cells.

PubMed

Kim, Ji-Yeon; Lee, Dong-Hyung; Joo, Jong-Kil; Jin, Jun-O; Wang, Ji-Won; Hong, Young-Seoub; Kwak, Jong-Young; Lee, Kyu-Sup

2009-09-01

Intraperitoneal immuno-inflammatory changes may be associated with the pathogenesis of endometriosis. We evaluated the effects of peritoneal fluid obtained from patients with endometriosis (ePF) on the release of interferon-gamma-induced protein-10 (IP-10/CXCL10) and interleukin-8 (IL-8/CXCL8) by neutrophils, CD4(+) T cells, and monocytes. Neutrophils, CD4(+) T cells, and monocytes were cultured with ePF and the chemokine levels in the supernatants were then measured using enzyme-linked immunosorbent assay. The addition of ePF to cultures of CD4(+) T cells led to a significant increase in the release of IP-10 when compared with control PF without endometriosis (cPF). There was a positive correlation between the levels of IL-8 and IP-10 in ePF (R = 0.89, P = 0.041), but not between the levels of IP-10 and IL-8 released by neutrophils, CD4(+) T cells, and monocytes. The levels of IP-10 in ePF were positively correlated with the release of IP-10 by ePF-treated neutrophils (R = 0.89, P < 0.001), CD4(+) T cells (R = 0.93, P < 0.001), and monocytes (R = 0.70, P = 0.01). Moreover, the addition of ePF significantly enhanced the interferon-gamma-induced release of IP-10 by nuetrophils and CD4(+) T cells. These findings suggest that neutrophils and T cells release differential levels of IP-10 and IL-8 in response to stimulation with ePF, and that these cells are a major source of IP-10 in the PF of endometriosis patients.

The effects of 18β-glycyrrhetinic acid and glycyrrhizin on intestinal absorption of paeoniflorin using the everted rat gut sac model.

PubMed

He, Rui; Xu, Yongsong; Peng, Jingjing; Ma, Tingting; Li, Jing; Gong, Muxin

2017-01-01

Paeoniflorin (PF), the main active component of Shaoyao-Gancao-tang, possesses significantly antinociceptive effects and many other pharmacological activities. However, its poor intestinal absorption results in low bioavailability. Therefore, enhancing PF absorption plays a vital role in exerting its therapeutic effect. Shaoyao combined with Gancao exhibited a synergistic effect. The enhancement of PF absorption through the interaction of its constituents in intestinal absorption would be greatly implicated. The present study aimed at investigating the effects of glycyrrhizin, the main constituent of Gancao, and its main metabolite, 18β-glycyrrhetinic acid (18β-GA), on the intestinal absorptive behavior of PF, and the role of P-glycoprotein (P-gp) in PF absorption using the in vitro everted rat gut sac model. The results demonstrated that 1 mM of 18β-GA significantly increased PF absorption in both the jejunum and the ileum, while 100 μM of 18β-GA only promoted the ileum absorption and had no obvious effect on the jejunum absorption. The effect of glycyrrhizin on intestinal PF absorption was related to concentrations. One mM of glycyrrhizin significantly increased PF absorption in the jejunum after 45 min and in the ileum after 90 min. But 100 μM of glycyrrhizin had an inhibitory effect in the jejunum and no effect in the ileum before 60 min. Moreover, verapamil, the well-known P-gp inhibitor, could significantly enhance the PF absorption. In conclusion, the influence of 18β-GA and glycyrrhizin on the PF absorption was related to concentrations and intestinal segments. This might be involved in the intervention of efflux transport of PF mediated by intestinal P-gp.

Human autoantibodies against a desmosomal core protein in pemphigus foliaceus

PubMed Central

1984-01-01

Pemphigus foliaceus (PF) is a human autoimmune disease in which antibodies are directed against the cell surface of epidermal cells with resultant blister formation. The histopathology of these blisters indicates that cells have detached from each other, and electron microscopy of early blisters shows diminished numbers, to complete loss, of desmosomes as well as abnormalities of the tonofilament- desmosome complex. In this study we demonstrate that autoantibodies from certain PF patients bind to a desmosomal core glycoprotein called desmoglein (DG) I. Proteins in extracts of normal human epidermis were separated by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE), then transferred to nitrocellulose or 2- aminophenylthioether paper for immunoperoxidase staining. Results of these immunoblots indicated that sera from 6 of 13 PF patients specifically and intensely stained an approximately 160,000 mol wt polypeptide, "PF antigen". Such staining was not seen with normal human sera or sera from patients with pemphigus vulgaris or bullous pemphigoid, two autoimmune blistering skin diseases that are clinically, histologically, and immunochemically distinct from PF. However, rabbit antiserum directed against DGI, that was isolated from bovine muzzle desmosomes, stained a polypeptide band which co-migrated with PF antigen. Furthermore, when proteins from extracts of normal human epidermis were electrophoresed in two dimensions (isoelectric focusing, then SDS-PAGE) before transfer to nitrocellulose for immunoperoxidase staining, PF antibodies and antibodies to DGI stained identical spots. Finally, PF sera as well as PF IgG that was affinity purified with PF antigen from normal human epidermis, both selectively bound to DGI extracted from bovine muzzle desmosomes. These studies demonstrate that the human autoantibodies from certain patients with PF, a disease of epidermal cell adhesion, are directed against a desmosomal core protein. PMID:6491602

Somatic cells initiate primordial follicle activation and govern the development of dormant oocytes in mice.

PubMed

Zhang, Hua; Risal, Sanjiv; Gorre, Nagaraju; Busayavalasa, Kiran; Li, Xin; Shen, Yan; Bosbach, Benedikt; Brännström, Mats; Liu, Kui

2014-11-03

The majority of oocytes in the mammalian ovary are dormant oocytes that are enclosed in primordial follicles by several somatic cells, which we refer to as primordial follicle granulosa cells (pfGCs). Very little is known, however, about how the pfGCs control the activation of primordial follicles and the developmental fates of dormant oocytes. By targeting molecules in pfGCs with several mutant mouse models, we demonstrate that the somatic pfGCs initiate the activation of primordial follicles and govern the quiescence or awakening of dormant oocytes. Inhibition of mTORC1 signaling in pfGCs prevents the differentiation of pfGCs into granulosa cells, and this arrests the dormant oocytes in their quiescent states, leading to oocyte death. Overactivation of mTORC1 signaling in pfGCs accelerates the differentiation of pfGCs into granulosa cells and causes premature activation of all dormant oocytes and primordial follicles. We further show that pfGCs trigger the awakening of dormant oocytes through KIT ligand (KITL), and we present an essential communication network between the somatic cells and germ cells that is based on signaling between the mTORC1-KITL cascade in pfGCs and KIT-PI3K signaling in oocytes. Our findings provide a relatively complete picture of how mammalian primordial follicles are activated. The microenvironment surrounding primordial follicles can activate mTORC1-KITL signaling in pfGCs, and these cells trigger the awakening of dormant oocytes and complete the process of follicular activation. Such communication between the microenvironment, somatic cells, and germ cells is essential to maintaining the proper reproductive lifespan in mammals. Copyright © 2014 Elsevier Ltd. All rights reserved.

Assessment of the Plasmodium falciparum Preerythrocytic Antigen UIS3 as a Potential Candidate for a Malaria Vaccine.

PubMed

Longley, Rhea J; Halbroth, Benedict R; Salman, Ahmed M; Ewer, Katie J; Hodgson, Susanne H; Janse, Chris J; Khan, Shahid M; Hill, Adrian V S; Spencer, Alexandra J

2017-03-01

Efforts are under way to improve the efficacy of subunit malaria vaccines through assessments of new adjuvants, vaccination platforms, and antigens. In this study, we further assessed the Plasmodium falciparum antigen upregulated in infective sporozoites 3 (PfUIS3) as a vaccine candidate. PfUIS3 was expressed in the viral vectors chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) and used to immunize mice in a prime-boost regimen. We previously demonstrated that this regimen could provide partial protection against challenge with chimeric P. berghei parasites expressing PfUIS3. We now show that ChAd63-MVA PfUIS3 can also provide partial cross-species protection against challenge with wild-type P. berghei parasites. We also show that PfUIS3-specific cellular memory responses could be recalled in human volunteers exposed to P. falciparum parasites in a controlled human malaria infection study. When ChAd63-MVA PfUIS3 was coadministered with the vaccine candidate P. falciparum thrombospondin-related adhesion protein (PfTRAP) expressed in the ChAd63-MVA system, there was no significant change in immunogenicity to either vaccine. However, when mice were challenged with double chimeric P. berghei - P. falciparum parasites expressing both PfUIS3 and PfTRAP, vaccine efficacy was improved to 100% sterile protection. This synergistic effect was evident only when the two vaccines were mixed and administered at the same site. We have therefore demonstrated that vaccination with PfUIS3 can induce a consistent delay in patent parasitemia across mouse strains and against chimeric parasites expressing PfUIS3 as well as wild-type P. berghei ; when this vaccine is combined with another partially protective regimen (ChAd63-MVA PfTRAP), complete protection is induced. Copyright © 2017 Longley et al.

Advancing Global Health through Development and Clinical Trials Partnerships: A Randomized, Placebo-Controlled, Double-Blind Assessment of Safety, Tolerability, and Immunogenicity of PfSPZ Vaccine for Malaria in Healthy Equatoguinean Men

PubMed Central

Olotu, Ally; Urbano, Vicente; Hamad, Ali; Eka, Martin; Chemba, Mwajuma; Nyakarungu, Elizabeth; Raso, Jose; Eburi, Esther; Mandumbi, Dolores O.; Hergott, Dianna; Maas, Carl D.; Ayekaba, Mitoha O.; Milang, Diosdado N.; Rivas, Matilde R.; Schindler, Tobias; Embon, Oscar M.; Ruben, Adam J.; Saverino, Elizabeth; Abebe, Yonas; KC, Natasha; James, Eric R.; Murshedkar, Tooba; Manoj, Anita; Chakravarty, Sumana; Li, Minglin; Adams, Matthew; Schwabe, Christopher; Segura, J. Luis; Daubenberger, Claudia; Tanner, Marcel; Richie, Thomas L.; Billingsley, Peter F.; Lee Sim, B. Kim; Abdulla, Salim; Hoffman, Stephen L.

2018-01-01

Abstract. Equatorial Guinea (EG) has implemented a successful malaria control program on Bioko Island. A highly effective vaccine would be an ideal complement to this effort and could lead to halting transmission and eliminating malaria. Sanaria® PfSPZ Vaccine (Plasmodium falciparum sporozoite Vaccine) is being developed for this purpose. To begin the process of establishing the efficacy of and implementing a PfSPZ Vaccine mass vaccination program in EG, we decided to conduct a series of clinical trials of PfSPZ Vaccine on Bioko Island. Because no clinical trial had ever been conducted in EG, we first successfully established the ethical, regulatory, quality, and clinical foundation for conducting trials. We now report the safety, tolerability, and immunogenicity results of the first clinical trial in the history of the country. Thirty adult males were randomized in the ratio 2:1 to receive three doses of 2.7 × 105 PfSPZ of PfSPZ Vaccine (N = 20) or normal saline placebo (N = 10) by direct venous inoculation at 8-week intervals. The vaccine was safe and well tolerated. Seventy percent, 65%, and 45% of vaccinees developed antibodies to Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) by enzyme-linked immunosorbent assay, PfSPZ by automated immunofluorescence assay, and PfSPZ by inhibition of sporozoite invasion assay, respectively. Antibody responses were significantly lower than responses in U.S. adults who received the same dosage regimen, but not significantly different than responses in young adult Malians. Based on these results, a clinical trial enrolling 135 subjects aged 6 months to 65 years has been initiated in EG; it includes PfSPZ Vaccine and first assessment in Africa of PfSPZ-CVac. ClinicalTrials.gov identifier: NCT02418962. PMID:29141739

Dose-Related Target Occupancy and Effects on Circuitry, Behavior, and Neuroplasticity of the Glycine Transporter-1 Inhibitor PF-03463275 in Healthy and Schizophrenia Subjects.

PubMed

D'Souza, Deepak Cyril; Carson, Richard E; Driesen, Naomi; Johannesen, Jason; Ranganathan, Mohini; Krystal, John H

2018-01-31

Glycine transporter-1 (GlyT1) inhibitors may ameliorate cognitive impairments associated with schizophrenia. The dose-related occupancy and target engagement of the GlyT1 inhibitor PF-03463275 were studied to inform optimal dose selection for a clinical trial for cognitive impairments associated with schizophrenia. In substudy 1, the effects of PF-03463275 (10, 20, and 40 mg twice a day) on occupancy of GlyT1 were tested using positron emission tomography and 18 F-MK-6577, and visual long-term potentiation (LTP) in schizophrenia patients (SZs) and healthy control subjects. Furthermore, the capacity of PF-03463275 to attenuate ketamine-induced disruption of working memory-related activation of a "working memory" circuit was tested only in healthy control subjects using functional magnetic resonance imaging. Subsequently, the effects of PF-03463275 (60 mg twice a day) on occupancy of GlyT1 and long-term potentiation were examined only in SZs (substudy 2). PF-03463275 at 10, 20, 40, and 60 mg twice a day produced ∼44%, 61%, 76%, and 83% GlyT1 occupancy, respectively, in SZs with higher ligand binding to GlyT1 in subcortical versus cortical regions. PF-03463275 did not attenuate any ketamine-induced effects but did improve working memory accuracy in healthy control subjects. PF-03463275 increased long-term potentiation only in SZs with peak effects at 40 mg twice a day (∼75% GlyT1 occupancy) and with a profile suggestive of an inverted U dose response. PF-03463275 was well-tolerated. The dose-related GlyT1 occupancy of PF-03463275 is linear. While PF-03463275 did not show evidence of facilitating N-methyl-D-aspartate receptor function in the ketamine assay, it enhanced neuroplasticity in SZs. These findings provide support for a clinical trial to test the ability of PF-03463275 to enhance cognitive remediation toward addressing cognitive impairments associated with schizophrenia. Published by Elsevier Inc.

Polypeptide Translocation Through the Mitochondrial TOM Channel: Temperature-Dependent Rates at the Single-Molecule Level.

PubMed

Mahendran, Kozhinjampara R; Lamichhane, Usha; Romero-Ruiz, Mercedes; Nussberger, Stephan; Winterhalter, Mathias

2013-01-03

The TOM protein complex facilitates the transfer of nearly all mitochondrial preproteins across outer mitochondrial membranes. Here we characterized the effect of temperature on facilitated translocation of a mitochondrial presequence peptide pF1β. Ion current fluctuations analysis through single TOM channels revealed thermodynamic and kinetic parameters of substrate binding and allowed determining the energy profile of peptide translocation. The activation energy for the on-rate and off-rate of the presequence peptide into the TOM complex was symmetric with respect to the electric field and estimated to be about 15 and 22 kT per peptide. These values are above that expected for free diffusion of ions in water (6 kT) and reflect the stronger interaction in the channel. Both values are in the range for typical enzyme kinetics and suggest one process without involving large conformational changes within the channel protein.

Elucidation of Transport Mechanism of Paeoniflorin and the Influence of Ligustilide, Senkyunolide I and Senkyunolide A on Paeoniflorin Transport through Mdck-Mdr1 Cells as Blood-Brain Barrier in Vitro Model.

PubMed

Hu, Peng-Yi; Liu, Dan; Zheng, Qin; Wu, Qing; Tang, Yu; Yang, Ming

2016-03-02

The objectives of the present investigation were to: (1) elucidate the transport mechanism of paeoniflorin (PF) across MDCK-MDR1 monolayers; and (2) evaluate the effect of ligustilide (LIG), senkyunolide I (SENI) and senkyunolide A (SENA) on the transport of PF through blood-brain barrier so as to explore the enhancement mechanism. Transport studies of PF were performed in both directions, from apical to basolateral side (A→B) and from basolateral to apical sides (B→A). Drug concentrations were analyzed by LC-MS/MS. PF showed relatively poor absorption in MDCK-MDR1 cells, apparent permeability coefficients (Papp) ranging from 0.587 × 10(-6) to 0.705 × 10(-6) cm/s. In vitro experiments showed that the transport of PF in both directions was concentration dependent and not saturable. The B→A/A→B permeability ER of PF was more than 2 in the MDCK-MDR1 cells, which indicated that the transport mechanism of PF might be passive diffusion as the dominating process with the active transportation mediated mechanism involved. The increased Papp of PF in A→B direction by EDTA-Na₂ suggested that PF was absorbed via the paracellular route. The P-gp inhibitor verapamil could significantly increase the transport of PF in A→B direction, and ER decreased from 2.210 to 0.690, which indicated that PF was P-gp substance. The transport of PF in A→B direction significantly increased when co-administrated with increasing concentrations of LIG, SENI and SENA. An increased cellular accumulation of Rho 123 and Western blot analysis indicated that LIG, SENI and SENA had increased the transport of PF in the BBB models attribute to down-regulate P-gp expression. A decrease in transepithelial electrical resistance (TEER) during the permeation experiment can be explained by the modulation and opening of the tight junctions caused by the permeation enhancer LIG, SENI and SENA.

Moxifloxacin pharmacokinetics and pleural fluid penetration in patients with pleural effusion.

PubMed

Chatzika, Kalliopi; Manika, Katerina; Kontou, Paschalina; Pitsiou, Georgia; Papakosta, Despina; Zarogoulidis, Konstantinos; Kioumis, Ioannis

2014-01-01

The aim of this study was to evaluate the pharmacokinetics and penetration of moxifloxacin (MXF) in patients with various types of pleural effusion. Twelve patients with empyema/parapneumonic effusion (PPE) and 12 patients with malignant pleural effusion were enrolled in the study. A single-dose pharmacokinetic study was performed after intravenous administration of 400 mg MXF. Serial plasma (PL) and pleural fluid (PF) samples were collected during a 24-h time interval after drug administration. The MXF concentration in PL and PF was determined by high-performance liquid chromatography, and main pharmacokinetic parameters were estimated. Penetration of MXF in PF was determined by the ratio of the area under the concentration-time curve from time zero to 24 h (AUC24) in PF (AUC24PF) to the AUC24 in PL. No statistically significant differences in the pharmacokinetics in PL were observed between the two groups, despite the large interindividual variability in the volume of distribution, clearance, and elimination half-life. The maximum concentration in PF (CmaxPF) in patients with empyema/PPE was 2.23±1.31 mg/liter, and it was detected 7.50±2.39 h after the initiation of the infusion. In patients with malignant effusion, CmaxPF was 2.96±1.45 mg/liter, but it was observed significantly earlier, at 3.58±1.38 h (P<0.001). Both groups revealed similar values of AUC24PF (31.83±23.52 versus 32.81±12.66 mg·h/liter). Penetration of MXF into PF was similarly good in both patient groups (1.11±0.74 versus 1.17±0.39). Despite similar plasma pharmacokinetics, patients with empyema/parapneumonic effusion showed a significant delay in achievement of PF maximum MXF levels compared to those with malignant effusion. However, in both groups, the degree of MXF PF penetration and the on-site drug exposure, expressed by AUC24PF, did not differ according to the type of pleural effusion.

Bilateral comparison of 10 pF and 100 pF standards (ongoing BIPM key comparisons BIPM.EM-K14.a and 14.b) between the NMISA (South Africa) and the BIPM

NASA Astrophysics Data System (ADS)

Gournay, Pierre; Khoza, Michael

2017-01-01

This report presents the results of a bilateral comparison of 10 pF and 100 pF capacitance standards between the NMISA (South Africa) and the BIPM carried out in 2016. The comparison at 10 pF forms part of the ongoing BIPM key comparison BIPM.EM-K14.a and that at 100 pF of the ongoing BIPM key comparison BIPM.EM-K14.b. The BIPM is the pilot laboratory for both of these comparisons. Two 10 pF and 100 pF travelling standards belonging to the BIPM were used in this comparison carried out with an 'A-B-A' pattern of measurements. The standards were measured first at the BIPM for a period of about one month, then for a similar period at the NMISA, and finally again at the BIPM. The measurand was the two terminal-pair capacitance at a frequency of either 1000 Hz or 1592 Hz, for a measuring rms voltage of 15 V at 10 pF and 10 V at 100 pF. One of the 10 pF travelling standards had to be eliminated from the comparison due to a bistable behaviour, possibly due to transportation. The results from the NMISA and the BIPM at both 1000 Hz and 1592 Hz were found to be in good agreement, with a difference smaller than the relative expanded uncertainty (95 % confidence, k = 2) of maximum value 0.33 × 10-6 at 10 pF and 0.24 × 10-6 at 100 pF (and 1000 Hz in both cases). Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCEM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

A new world malaria map: Plasmodium falciparum endemicity in 2010.

PubMed

Gething, Peter W; Patil, Anand P; Smith, David L; Guerra, Carlos A; Elyazar, Iqbal R F; Johnston, Geoffrey L; Tatem, Andrew J; Hay, Simon I

2011-12-20

Transmission intensity affects almost all aspects of malaria epidemiology and the impact of malaria on human populations. Maps of transmission intensity are necessary to identify populations at different levels of risk and to evaluate objectively options for disease control. To remain relevant operationally, such maps must be updated frequently. Following the first global effort to map Plasmodium falciparum malaria endemicity in 2007, this paper describes the generation of a new world map for the year 2010. This analysis is extended to provide the first global estimates of two other metrics of transmission intensity for P. falciparum that underpin contemporary questions in malaria control: the entomological inoculation rate (PfEIR) and the basic reproductive number (PfR). Annual parasite incidence data for 13,449 administrative units in 43 endemic countries were sourced to define the spatial limits of P. falciparum transmission in 2010 and 22,212 P. falciparum parasite rate (PfPR) surveys were used in a model-based geostatistical (MBG) prediction to create a continuous contemporary surface of malaria endemicity within these limits. A suite of transmission models were developed that link PfPR to PfEIR and PfR and these were fitted to field data. These models were combined with the PfPR map to create new global predictions of PfEIR and PfR. All output maps included measured uncertainty. An estimated 1.13 and 1.44 billion people worldwide were at risk of unstable and stable P. falciparum malaria, respectively. The majority of the endemic world was predicted with a median PfEIR of less than one and a median PfRc of less than two. Values of either metric exceeding 10 were almost exclusive to Africa. The uncertainty described in both PfEIR and PfR was substantial in regions of intense transmission. The year 2010 has a particular significance as an evaluation milestone for malaria global health policy. The maps presented here contribute to a rational basis for control and elimination decisions and can serve as a baseline assessment as the global health community looks ahead to the next series of milestones targeted at 2015.

The Colletotrichum boninense species complex

PubMed Central

Damm, U.; Cannon, P.F.; Woudenberg, J.H.C.; Johnston, P.R.; Weir, B.S.; Tan, Y.P.; Shivas, R.G.; Crous, P.W.

2012-01-01

Although only recently described, Colletotrichum boninense is well established in literature as an anthracnose pathogen or endophyte of a diverse range of host plants worldwide. It is especially prominent on members of Amaryllidaceae, Orchidaceae, Proteaceae and Solanaceae. Reports from literature and preliminary studies using ITS sequence data indicated that C. boninense represents a species complex. A multilocus molecular phylogenetic analysis (ITS, ACT, TUB2, CHS-1, GAPDH, HIS3, CAL) of 86 strains previously identified as C. boninense and other related strains revealed 18 clades. These clades are recognised here as separate species, including C. boninense s. str., C. hippeastri, C. karstii and 12 previously undescribed species, C. annellatum, C. beeveri, C. brassicicola, C. brasiliense, C. colombiense, C. constrictum, C. cymbidiicola, C. dacrycarpi, C. novae-zelandiae, C. oncidii, C. parsonsiae and C. torulosum. Seven of the new species are only known from New Zealand, perhaps reflecting a sampling bias. The new combination C. phyllanthi was made, and C. dracaenae Petch was epitypified and the name replaced with C. petchii. Typical for species of the C. boninense species complex are the conidiogenous cells with rather prominent periclinal thickening that also sometimes extend to form a new conidiogenous locus or annellations as well as conidia that have a prominent basal scar. Many species in the C. boninense complex form teleomorphs in culture. Taxonomic novelties: New combination - Colletotrichum phyllanthi (H. Surendranath Pai) Damm, P.F. Cannon & Crous. Name replacement - C. petchii Damm, P.F. Cannon & Crous. New species - C. annellatum Damm, P.F. Cannon & Crous, C. beeveri Damm, P.F. Cannon, Crous, P.R. Johnst. & B. Weir, C. brassicicola Damm, P.F. Cannon & Crous, C. brasiliense Damm, P.F. Cannon, Crous & Massola, C. colombiense Damm, P.F. Cannon, Crous, C. constrictum Damm, P.F. Cannon, Crous, P.R. Johnst. & B. Weir, C. cymbidiicola Damm, P.F. Cannon, Crous, P.R. Johnst. & B. Weir, C. dacrycarpi Damm, P.F. Cannon, Crous, P.R. Johnst. & B. Weir, C. novae-zelandiae Damm, P.F. Cannon, Crous, P.R. Johnst. & B. Weir, C. oncidii Damm, P.F. Cannon & Crous, C. parsonsiae Damm, P.F. Cannon, Crous, P.R. Johnst. & B. Weir, C. torulosum Damm, P.F. Cannon, Crous, P.R. Johnst. & B. Weir. Typifications: Epitypifications - C. dracaenae Petch. PMID:23136457

Bipyrimidine ruthenium(II) arene complexes: structure, reactivity and cytotoxicity.

PubMed

Betanzos-Lara, Soledad; Novakova, Olga; Deeth, Robert J; Pizarro, Ana M; Clarkson, Guy J; Liskova, Barbora; Brabec, Viktor; Sadler, Peter J; Habtemariam, Abraha

2012-10-01

The synthesis and characterization of complexes [(η(6)-arene)Ru(N,N')X][PF(6)], where arene is para-cymene (p-cym), biphenyl (bip), ethyl benzoate (etb), hexamethylbenzene (hmb), indane (ind) or 1,2,3,4-tetrahydronaphthalene (thn), N,N' is 2,2'-bipyrimidine (bpm) and X is Cl, Br or I, are reported, including the X-ray crystal structures of [(η(6)-p-cym)Ru(bpm)I][PF(6)], [(η(6)-bip)Ru(bpm)Cl][PF(6)], [(η(6)-bip)Ru(bpm)I][PF(6)] and [(η(6)-etb)Ru(bpm)Cl][PF(6)]. Complexes in which N,N' is 1,10-phenanthroline (phen), 1,10-phenanthroline-5,6-dione or 4,7-diphenyl-1,10-phenanthroline (bathophen) were studied for comparison. The Ru(II) arene complexes undergo ligand-exchange reactions in aqueous solution at 310 K; their half-lives for hydrolysis range from 14 to 715 min. Density functional theory calculations on [(η(6)-p-cym)Ru(bpm)Cl][PF(6)], [(η(6)-p-cym)Ru(bpm)Br][PF(6)], [(η(6)-p-cym)Ru(bpm)I][PF(6)], [(η(6)-bip)Ru(bpm)Cl][PF(6)], [(η(6)-bip)Ru(bpm)Br][PF(6)] and [(η(6)-bip)Ru(bpm)I][PF(6)] suggest that aquation occurs via an associative pathway and that the reaction is thermodynamically favourable when the leaving ligand is I > Br ≈ Cl. pK (a)* values for the aqua adducts of the complexes range from 6.9 to 7.32. A binding preference for 9-ethylguanine (9-EtG) compared with 9-ethyladenine (9-EtA) was observed for [(η(6)-p-cym)Ru(bpm)Cl][PF(6)], [(η(6)-hmb)Ru(bpm)Cl](+), [(η(6)-ind)Ru(bpm)Cl](+), [(η(6)-thn)Ru(bpm)Cl](+), [(η(6)-p-cym)Ru(phen)Cl](+) and [(η(6)-p-cym)Ru(bathophen)Cl](+) in aqueous solution at 310 K. The X-ray crystal structure of the guanine complex [(η(6)-p-cym)Ru(bpm)(9-EtG-N7)][PF(6)](2) shows multiple hydrogen bonding. Density functional theory calculations show that the 9-EtG adducts of all complexes are thermodynamically preferred compared with those of 9-EtA. However, the bmp complexes are inactive towards A2780 human ovarian cancer cells. Calf thymus DNA interactions for [(η(6)-p-cym)Ru(bpm)Cl][PF(6)] and [(η(6)-p-cym)Ru(phen)Cl][PF(6)] consist of weak coordinative, intercalative and monofunctional coordination. Binding to biomolecules such as glutathione may play a role in deactivating the bpm complexes.

Inhibition of human megakaryocytopoiesis in vitro by platelet factor 4 (PF4) and a synthetic COOH-terminal PF4 peptide.

PubMed Central

Gewirtz, A M; Calabretta, B; Rucinski, B; Niewiarowski, S; Xu, W Y

1989-01-01

We report that highly purified human platelet factor 4 (PF4) inhibits human megakaryocytopoiesis in vitro. At greater than or equal to 25 micrograms/ml, PF4 inhibited megakaryocyte colony formation approximately 80% in unstimulated cultures, and approximately 58% in cultures containing recombinant human IL 3 and granulocyte-macrophage colony-stimulating factor. Because PF4 (25 micrograms/ml) had no effect on either myeloid or erythroid colony formation lineage specificity of this effect was suggested. A synthetic COOH-terminal PF4 peptide of 24, but not 13 residues, also inhibited megakaryocyte colony formation, whereas a synthetic 18-residue beta-thromboglobulin (beta-TG) peptide and native beta-TG had no such effect when assayed at similar concentrations. The mechanism of PF4-mediated inhibition was investigated. First, we enumerated total cell number, and examined cell maturation in control colonies (n = 200) and colonies (n = 100) that arose in PF4-containing cultures. Total cells per colony did not differ dramatically in the two groups (6.1 +/- 3.0 vs. 4.2 +/- 1.6, respectively), but the numbers of mature large cells per colony was significantly decreased in the presence of PF4 when compared with controls (1.6 +/- 1.5 vs. 3.9 +/- 2.3; P less than 0.001). Second, by using the human leukemia cell line HEL as a model for primitive megakaryocytic cells, we studied the effect of PF4 on cell doubling time, on the expression of both growth-regulated (H3, p53, c-myc,and c-myb), and non-growth-regulated (beta 2-microglobulin) genes. At high concentrations of native PF4 (50 micrograms/ml), no effect on cell doubling time, or H3 or p53 expression was discerned. In contrast, c-myc and c-myb were both upregulated. These results suggested the PF4 inhibited colony formation by impeding cell maturation, as opposed to cell proliferation, perhaps by inducing expression of c-myc and c-myb. The ability of PF4 to inhibit a normal cell maturation function was then tested. Megakaryocytes were incubated in synthetic PF4, or beta-TG peptides for 18 h and effect on Factor V steady-state mRNA levels was determined in 600 individual cells by in situ hybridization. beta-TG peptide had no effect on FV mRNA levels, whereas a approximately 60% decrease in expression of Factor V mRNA was found in megakaryocytes exposed to greater than or equal 100 ng/ml synthetic COOH-terminal PF4 peptide. Accordingly, PF4 modulates megakaryocyte maturation in vitro, and may function as a negative autocrine regulator of human megakaryocytopoiesis. Images PMID:2523411

NASA Astrophysics Data System (ADS)

Good, J.; Bracanovic, D.

The development of High Temperature Superconductors (HTS) conductors makes it possible to build very high field superconducting magnets up to at least 25 T. Previously, the only way to obtain a steady field of 25 T for research would be to use water cooled copper solenoids. To achieve 25 T in a 50 mm working space would require about 10 MW of power with a large water cooling plant to carry away the heat. With such high powers involved it is difficult to have a stable and quiet magnetic field environment in which to make sensitive measurements such as NMR. Both capital and operating costs are high so few such facilities exist worldwide. This makes a superconducting magnet of 25 T a very attractive proposition. Figure 1 shows that the critical current of HTS as compared to NbTi and NbSn. The latter can be used up to a limit of about 20 T at 4.2 K. The HTS on the other hand shows the potential of much higher fields. The two main issues in magnet design are the maximum critical current and the maximum stress that a conductor or coil structure can support. For the inner sections of the coil the forces are modest but as the diameter increases towards the outside of the coil hoop stress becomes the dominant issue. Cryogenic has built a magnet system with first generation BSCCO conductor. It is designed to run at 4.2 K. It has a three section design, two of conventional superconductor and one of HTS. • The outer winding is made from NbTi giving a field of 9 T, in a bore of 225 mm. The coil is made from 21 km of NbTi wire graded from 1 to 0.6 mm diameter. • A middle coil of NbSn bronze route conductor providing a field of 14 T in 140 mm diameter. • An inner set of HTS coils. These are in the form of 3 coaxial windings made from silver matrix BSCCO conductor supplied by American Superconductor. This conductor has a critical current of 100 A at 77 K in zero field. At 4 K in low field the current is very much higher. The set of three BSCCO windings has a gauss per amp of 157 and when run on its own at a current of 300 A provides a field of 4.7 T, although currents above 275 A begin to show significant resistive losses in the conductor. The inner BSCCO coils are separately powered from the outer magnet. In a test of the full magnet system the BSCCO coil is ramped up at various background fields up to 13 T. The resulting voltage loss across the BSCCO is shown in Fig. 2. This test shows that the BSCCO conductor can operate up to 275 A quite successfully independent of the background field with just a slight increase in resistive losses presumably from the joints between conductor being magneto-resistive or due to flux flow in the conductor. Since the BSCCO coils were made new 2nd generation conductors have become available made from thin films of YBCO on a stainless steel backing. These have a much higher effective current density. A 4 mm wide tape of BSCCO is 0.4 mm thick but carries a similar current to an YBCO tape of 0.01 mm or even 0.05 mm thickness. Table 1 shows the properties of different conductors compared. Interestingly the conductors are not just higher current density but also more flexible and stronger in tension. A new coil has now been produced from 0.1 mm Super Power material of a size that can fit inside the existing winding so that the combination can produce above 6 T providing a total field of 20 T at 4.2 K in a working bore of 38 mm. Now that the new 2nd generation YBCO based conductors have become available it is intended to exchange the BSCCO coils for YBCO windings which will allow this magnet to operate at much higher fields of up to 25 T. At this field it will be the highest field superconducting magnet worldwide. The magnet is housed in a liquid helium cryostat. To reduce helium consumption a powerful 2nd stage cryocooler is fitted to the cryostat. The first stage cools a shield around the liquid helium to 45 K. The second stage has a cooling power of 1.5 W at 4.2 K and is used to recondense helium gas evolved from the magnet. In operation, with no current in the leads to the cryocooler it is able to condense more gas than that evolved from the cryostat so the liquid helium level will increase with time. Except at the highest currents the cryostat is a zero loss magnet system. A cross section of cryostat and magnet is show in Fig 3. The power required for the cryocooler is 6.5 kW while that for the magnet power supplies and ancillary electronics is 2 kW giving a combined power requirement of 8.5 kW. This compares very favourably with the typical value of 10 MW required by a water cooled copper solenoid to achieve the same field. Note from Publisher: This article contains the abstract only.

Correlation of Resistance to Proflavine and Penicillin in Escherichia coli

PubMed Central

McKellar, Robin C.; McKenzie, Colin N.; Kushner, Donn J.

1976-01-01

A number of proflavine (PF)-resistant mutants of Escherichia coli B were also resistant to penicillin and cephalothin. Mutants resistant to 1.0 mM PF were 10 times more penicillin resistant than were the PF-susceptible, wild-type cells. Single-step mutants selected for resistance to either PF or penicillin were also resistant to the other drug. None of the resistant mutants tested possessed β-lactamase activity. These results suggest that resistance to PF and penicillin in E. coli B may be due to permeability changes in the cell envelope. PMID:791110

Hematological and biochemical features of postpartum fever in the heavy draft mare.

PubMed

Aoki, Takahiro; Kimura, Yuki; Oya, Anna; Chiba, Akiko; Ishii, Mitsuo; Nambo, Yasuo

2016-01-01

Heavy draft mares potentially have a higher risk of suffering from postpartum fever (PF) than light breed mares. The purpose of this study was to compare hematological and biochemical features between clinically healthy mares (n=40) and PF-affected mares (n=16). Mares were classified as having PF when their rectal temperature rose to >38.5°C within 96 hr of foaling. The numbers of leukocytes, lymphocytes, and neutrophils and the serum magnesium level were significantly lower in PF-affected mares. The serum SAA and NEFA levels were significantly higher in PF-affected mares. Strong inflammation responses, fat mobilization associated with negative energy balance and possibly endotoxin participate in hematological and biochemical features of PF in heavy draft mares.

BabyMEG: A whole-head pediatric magnetoencephalography system for human brain development research

NASA Astrophysics Data System (ADS)

Okada, Yoshio; Hämäläinen, Matti; Pratt, Kevin; Mascarenas, Anthony; Miller, Paul; Han, Menglai; Robles, Jose; Cavallini, Anders; Power, Bill; Sieng, Kosal; Sun, Limin; Lew, Seok; Doshi, Chiran; Ahtam, Banu; Dinh, Christoph; Esch, Lorenz; Grant, Ellen; Nummenmaa, Aapo; Paulson, Douglas

2016-09-01

We developed a 375-channel, whole-head magnetoencephalography (MEG) system ("BabyMEG") for studying the electrophysiological development of human brain during the first years of life. The helmet accommodates heads up to 95% of 36-month old boys in the USA. The unique two-layer sensor array consists of: (1) 270 magnetometers (10 mm diameter, ˜15 mm coil-to-coil spacing) in the inner layer, (2) thirty-five three-axis magnetometers (20 mm × 20 mm) in the outer layer 4 cm away from the inner layer. Additionally, there are three three-axis reference magnetometers. With the help of a remotely operated position adjustment mechanism, the sensor array can be positioned to provide a uniform short spacing (mean 8.5 mm) between the sensor array and room temperature surface of the dewar. The sensors are connected to superconducting quantum interference devices (SQUIDs) operating at 4.2 K with median sensitivity levels of 7.5 fT/√Hz for the inner and 4 fT/√Hz for the outer layer sensors. SQUID outputs are digitized by a 24-bit acquisition system. A closed-cycle helium recycler provides maintenance-free continuous operation, eliminating the need for helium, with no interruption needed during MEG measurements. BabyMEG with the recycler has been fully operational from March, 2015. Ongoing spontaneous brain activity can be monitored in real time without interference from external magnetic noise sources including the recycler, using a combination of a lightly shielded two-layer magnetically shielded room, an external active shielding, a signal-space projection method, and a synthetic gradiometer approach. Evoked responses in the cortex can be clearly detected without averaging. These new design features and capabilities represent several advances in MEG, increasing the utility of this technique in basic neuroscience as well as in clinical research and patient studies.

BabyMEG: A whole-head pediatric magnetoencephalography system for human brain development research.

PubMed

Okada, Yoshio; Hämäläinen, Matti; Pratt, Kevin; Mascarenas, Anthony; Miller, Paul; Han, Menglai; Robles, Jose; Cavallini, Anders; Power, Bill; Sieng, Kosal; Sun, Limin; Lew, Seok; Doshi, Chiran; Ahtam, Banu; Dinh, Christoph; Esch, Lorenz; Grant, Ellen; Nummenmaa, Aapo; Paulson, Douglas

2016-09-01

We developed a 375-channel, whole-head magnetoencephalography (MEG) system ("BabyMEG") for studying the electrophysiological development of human brain during the first years of life. The helmet accommodates heads up to 95% of 36-month old boys in the USA. The unique two-layer sensor array consists of: (1) 270 magnetometers (10 mm diameter, ∼15 mm coil-to-coil spacing) in the inner layer, (2) thirty-five three-axis magnetometers (20 mm × 20 mm) in the outer layer 4 cm away from the inner layer. Additionally, there are three three-axis reference magnetometers. With the help of a remotely operated position adjustment mechanism, the sensor array can be positioned to provide a uniform short spacing (mean 8.5 mm) between the sensor array and room temperature surface of the dewar. The sensors are connected to superconducting quantum interference devices (SQUIDs) operating at 4.2 K with median sensitivity levels of 7.5 fT/√Hz for the inner and 4 fT/√Hz for the outer layer sensors. SQUID outputs are digitized by a 24-bit acquisition system. A closed-cycle helium recycler provides maintenance-free continuous operation, eliminating the need for helium, with no interruption needed during MEG measurements. BabyMEG with the recycler has been fully operational from March, 2015. Ongoing spontaneous brain activity can be monitored in real time without interference from external magnetic noise sources including the recycler, using a combination of a lightly shielded two-layer magnetically shielded room, an external active shielding, a signal-space projection method, and a synthetic gradiometer approach. Evoked responses in the cortex can be clearly detected without averaging. These new design features and capabilities represent several advances in MEG, increasing the utility of this technique in basic neuroscience as well as in clinical research and patient studies.

Patellar maltracking is prevalent among patellofemoral pain subjects with patella alta: an upright, weightbearing MRI study

PubMed Central

Pal, Saikat; Besier, Thor F.; Beaupre, Gary S.; Fredericson, Michael; Delp, Scott L.; Gold, Garry E.

2012-01-01

The purpose of this study is to determine if patellar maltracking is more prevalent among patellofemoral (PF) pain subjects with patella alta compared to subjects with normal patella height. We imaged 37 PF pain and 15 pain free subjects in an open-configuration magnetic resonance imaging scanner while they stood in a weightbearing posture. We measured patella height using the Caton-Deschamps, Blackburne-Peel, Insall-Salvati, Modified Insall-Salvati, and Patellotrochlear indices, and classified the subjects into patella alta and normal patella height groups. We measured patella tilt and bisect offset from oblique-axial plane images, and classified the subjects into maltracking and normal tracking groups. Patellar maltracking was more prevalent among PF pain subjects with patella alta compared to PF pain subjects with normal patella height (two-tailed Fisher’s exact test, p < 0.050). Using the Caton-Deschamps index, 67% (8/12) of PF pain subjects with patella alta were maltrackers, whereas only 16% (4/25) of PF pain subjects with normal patella height were maltrackers. Patellofemoral pain subjects classified as maltrackers displayed a greater patella height compared to the pain free and PF pain subjects classified as normal trackers (two-tailed unpaired t-tests with Bonferroni correction, p < 0.017). This study adds to our understanding of PF pain in two ways - 1) we demonstrate that patellar maltracking is more prevalent in PF pain subjects with patella alta compared to subjects with normal patella height; and 2) we show greater patella height in PF pain subjects compared to pain free subjects using four indices commonly used in clinics. PMID:23165335

The Crystal Structure of PF-8, the DNA Polymerase Accessory Subunit from Kaposi's Sarcoma-Associated Herpesvirus

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

Baltz, Jennifer L.; Filman, David J.; Ciustea, Mihai

2009-12-01

Kaposi's sarcoma-associated herpesvirus is an emerging pathogen whose mechanism of replication is poorly understood. PF-8, the presumed processivity factor of Kaposi's sarcoma-associated herpesvirus DNA polymerase, acts in combination with the catalytic subunit, Pol-8, to synthesize viral DNA. We have solved the crystal structure of residues 1 to 304 of PF-8 at a resolution of 2.8 {angstrom}. This structure reveals that each monomer of PF-8 shares a fold common to processivity factors. Like human cytomegalovirus UL44, PF-8 forms a head-to-head dimer in the form of a C clamp, with its concave face containing a number of basic residues that are predictedmore » to be important for DNA binding. However, there are several differences with related proteins, especially in loops that extend from each monomer into the center of the C clamp and in the loops that connect the two subdomains of each protein, which may be important for determining PF-8's mode of binding to DNA and to Pol-8. Using the crystal structures of PF-8, the herpes simplex virus catalytic subunit, and RB69 bacteriophage DNA polymerase in complex with DNA and initial experiments testing the effects of inhibition of PF-8-stimulated DNA synthesis by peptides derived from Pol-8, we suggest a model for how PF-8 might form a ternary complex with Pol-8 and DNA. The structure and the model suggest interesting similarities and differences in how PF-8 functions relative to structurally similar proteins.« less

Immune complexes formed following the binding of anti–platelet factor 4 (CXCL4) antibodies to CXCL4 stimulate human neutrophil activation and cell adhesion

PubMed Central

Xiao, Zhihua; Visentin, Gian P.; Dayananda, Kannayakanahalli M.

2008-01-01

We tested the possibility that immune complexes formed following platelet factor 4 (PF4/CXCL4) binding to anti-PF4 antibody can stimulate neutrophil activation, similar to previous reports with platelets. Monoclonal Abs against PF4 and IgG from a heparin-induced thrombocytopenia (HIT) patient were applied. We observed that although PF4 or anti-PF4 antibody alone did not alter neutrophil function, costimulation with both reagents resulted in approximately 3-fold increase in cell surface Mac-1 expression, enhanced cell adhesion via L-selectin and CD18 integrins, and degranulation of secondary and tertiary granules. The level of Mac-1 up-regulation peaked at an intermediate PF4 dose, suggesting that functional response varies with antigen-antibody stoichiometry. PF4 binding to neutrophils was blocked by chondroitinase ABC. Cell activation was inhibited by both chondroitinase ABC and anti-CD32/FcγRII blocking mAb, IV.3. Confocal microscopy demonstrated that immune complexes colocalize with CD32a. Studies with HIT IgG demonstrated that neutrophils could be activated in the absence of exogenous heparin. These data, together, show that leukocyte surface chondroitin sulfates promote neutrophil activation by enhancing immune-complex binding to CD32a. Studies with recombinant PF4 suggest a role for arginine 49 in stabilizing PF4-chondroitin binding. Neutrophils activated via this mechanism may contribute to thrombosis and inflammation in patients mounting an immune response to PF4-heparin. PMID:18539895

The impact of combined pulmonary fibrosis and chronic obstructive pulmonary disease on long-term survival after lung cancer surgery.

PubMed

Sekine, Yasuo; Sakairi, Yuichi; Yoshino, Mitsuru; Koh, Eitetsu; Hata, Atsushi; Suzuki, Hidemi; Yoshino, Ichiro

2014-06-01

The purpose of this study was to determine the impact of pulmonary fibrosis (PF) on postoperative complications and on long-term survival after surgical resection in lung cancer patients with chronic obstructive pulmonary disease (COPD). A retrospective chart review was conducted of 380 patients with COPD who had undergone pulmonary resection for lung cancer at the University Hospital between 1990 and 2005. The definition of COPD was a preoperative forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio of less than 70%; PF was defined as obvious bilateral fibrous change in the lower lung fields, confirmed by computed tomography. PF was present in 41 patients (10.8%) with COPD; the remaining 339 patients (89.2%) did not have PF. The preoperative FVC/FEV1 was significantly lower in the group of patients with PF than in the group without (p < 0.05). Acute lung injury and home oxygen therapy were significantly more common in the PF group; however, the 30-day mortality was similar between the groups. The cumulative survival at 3 and 5 years was 53.6 and 36.9%, respectively, in the PF group and 71.4 and 66.1%, respectively, in the non-PF group (p = 0.0009). Increased age, decreased body mass index, advanced pathologic stage, and the existence of PF were identified as independent risk factors for decreased survival. PF is a risk factor for decreased survival after surgical treatment in lung cancer patients with COPD. Georg Thieme Verlag KG Stuttgart · New York.

Pseudomonas protegens Pf-5 causes discoloration and pitting of mushroom caps due to the production of antifungal metabolites.

PubMed

Henkels, Marcella D; Kidarsa, Teresa A; Shaffer, Brenda T; Goebel, Neal C; Burlinson, Peter; Mavrodi, Dmitri V; Bentley, Michael A; Rangel, Lorena I; Davis, Edward W; Thomashow, Linda S; Zabriskie, T Mark; Preston, Gail M; Loper, Joyce E

2014-07-01

Bacteria in the diverse Pseudomonas fluorescens group include rhizosphere inhabitants known for their antifungal metabolite production and biological control of plant disease, such as Pseudomonas protegens Pf-5, and mushroom pathogens, such as Pseudomonas tolaasii. Here, we report that strain Pf-5 causes brown, sunken lesions on peeled caps of the button mushroom (Agaricus bisporus) that resemble brown blotch symptoms caused by P. tolaasii. Strain Pf-5 produces six known antifungal metabolites under the control of the GacS/GacA signal transduction system. A gacA mutant produces none of these metabolites and did not cause lesions on mushroom caps. Mutants deficient in the biosynthesis of the antifungal metabolites 2,4-diacetylphloroglucinol and pyoluteorin caused less-severe symptoms than wild-type Pf-5 on peeled mushroom caps, whereas mutants deficient in the production of lipopeptide orfamide A caused similar symptoms to wild-type Pf-5. Purified pyoluteorin and 2,4-diacetylphloroglucinol mimicked the symptoms caused by Pf-5. Both compounds were isolated from mushroom tissue inoculated with Pf-5, providing direct evidence for their in situ production by the bacterium. Although the lipopeptide tolaasin is responsible for brown blotch of mushroom caused by P. tolaasii, P. protegens Pf-5 caused brown blotch-like symptoms on peeled mushroom caps through a lipopeptide-independent mechanism involving the production of 2,4-diacetylphloroglucinol and pyoluteorin.

Novel mucus-penetrating liposomes as a potential oral drug delivery system: preparation, in vitro characterization, and enhanced cellular uptake

PubMed Central

Li, Xiuying; Chen, Dan; Le, Chaoyi; Zhu, Chunliu; Gan, Yong; Hovgaard, Lars; Yang, Mingshi

2011-01-01

Background The aim of this study was to investigate the intestinal mucus-penetrating properties and intestinal cellular uptake of two types of liposomes modified by Pluronic F127 (PF127). Methods The two types of liposomes, ie, PF127-inlaid liposomes and PF127-adsorbed liposomes, were prepared by a thin-film hydration method followed by extrusion, in which coumarin 6 was loaded as a fluorescence marker. A modified Franz diffusion cell mounted with the intestinal mucus of rats was used to study the diffusion characteristics of the two types of PF127 liposomes. Cell uptake studies were conducted in Caco-2 cells and analyzed using confocal laser scanning microcopy as well as flow cytometry. Results The diffusion efficiency of the two types of PF127-modified liposomes through intestinal rat mucus was 5–7-fold higher than that of unmodified liposomes. Compared with unmodified liposomes, PF127-inlaid liposomes showed significantly higher cellular uptake of courmarin 6. PF127-adsorbed liposomes showed a lower cellular uptake. Moreover, and interestingly, the two types of PF127-modified liposomes showed different cellular uptake mechanisms in Caco-2 cells. Conclusion PF127-inlaid liposomes with improved intestinal mucus-penetrating ability and enhanced cellular uptake might be a potential carrier candidate for oral drug delivery. PMID:22163166

Multi-omics Based Identification of Specific Biochemical Changes Associated With PfKelch13-Mutant Artemisinin-Resistant Plasmodium falciparum.

PubMed

Siddiqui, Ghizal; Srivastava, Anubhav; Russell, Adrian S; Creek, Darren J

2017-05-01

The emergence of artemisinin resistance in the malaria parasite Plasmodium falciparum poses a major threat to the control and elimination of malaria. Certain point mutations in the propeller domain of PfKelch13 are associated with resistance, but PfKelch13 mutations do not always result in clinical resistance. The underlying mechanisms associated with artemisinin resistance are poorly understood, and the impact of PfKelch13 mutations on cellular biochemistry is not defined. This study aimed to identify global biochemical differences between PfKelch13-mutant artemisinin-resistant and -sensitive strains of P. falciparum by combining liquid chromatography-mass spectrometry (LC-MS)-based proteomics, peptidomics, and metabolomics. Proteomics analysis found both PfKelch13 mutations examined to be specifically associated with decreased abundance of PfKelch13 protein. Metabolomics analysis demonstrated accumulation of glutathione and its precursor, gamma-glutamylcysteine, and significant depletion of 1 other putative metabolite in resistant strains. Peptidomics analysis revealed lower abundance of several endogenous peptides derived from hemoglobin (HBα and HBβ) in the artemisinin-resistant strains. PfKelch13 mutations associated with artemisinin resistance lead to decreased abundance of PfKelch13 protein, decreased hemoglobin digestion, and enhanced glutathione production. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Dynamometer-based measure of spasticity confirms limited association between plantarflexor spasticity and walking function in persons with multiple sclerosis

PubMed Central

Kremer, Theodore R.; Van Dillen, Linda R.; Wagner, Joanne M.

2017-01-01

The literature shows inconsistent evidence regarding the association between clinically assessed plantarflexor (PF) spasticity and walking function in ambulatory persons with multiple sclerosis (pwMS). The use of a dynamometer-based spasticity measure (DSM) may help to clarify this association. Our cohort included 42 pwMS (27 female, 15 male; age: 42.9 +/− 10.2 yr) with mild clinical disability (Expanded Disability Status Scale score: 3.6 +/− 1.6). PF spasticity was assessed using a clinical measure, the modified Ashworth Scale (MAS), and an instrumented measure, the DSM. Walking function was assessed by the timed 25-foot walk test (T25FWT), the 6-minute walk test (6MWT), and the 12-item Multiple Sclerosis Walking Scale (MSWS-12). Spearman rho correlations were used to evaluate relationships between spasticity measures, measures of walking speed and endurance, and self-perceived limitations in walking. The correlation was small between PF spasticity and the T25FWT (PF maximum [Max] MAS rho = 0.27, PF Max DSM rho = 0.26), the 6MWT (PF Max MAS rho = −0.20, PF Max DSM rho = −0.21), and the MSWS-12 (PF Max MAS rho = 0.11, PF Max DSM rho = 0.26). Our results are similar to reports in other neurologic clinical populations, wherein spasticity has a limited association with walking dysfunction. PMID:25356797

Development of a copula-based particle filter (CopPF) approach for hydrologic data assimilation under consideration of parameter interdependence

NASA Astrophysics Data System (ADS)

Fan, Y. R.; Huang, G. H.; Baetz, B. W.; Li, Y. P.; Huang, K.

2017-06-01

In this study, a copula-based particle filter (CopPF) approach was developed for sequential hydrological data assimilation by considering parameter correlation structures. In CopPF, multivariate copulas are proposed to reflect parameter interdependence before the resampling procedure with new particles then being sampled from the obtained copulas. Such a process can overcome both particle degeneration and sample impoverishment. The applicability of CopPF is illustrated with three case studies using a two-parameter simplified model and two conceptual hydrologic models. The results for the simplified model indicate that model parameters are highly correlated in the data assimilation process, suggesting a demand for full description of their dependence structure. Synthetic experiments on hydrologic data assimilation indicate that CopPF can rejuvenate particle evolution in large spaces and thus achieve good performances with low sample size scenarios. The applicability of CopPF is further illustrated through two real-case studies. It is shown that, compared with traditional particle filter (PF) and particle Markov chain Monte Carlo (PMCMC) approaches, the proposed method can provide more accurate results for both deterministic and probabilistic prediction with a sample size of 100. Furthermore, the sample size would not significantly influence the performance of CopPF. Also, the copula resampling approach dominates parameter evolution in CopPF, with more than 50% of particles sampled by copulas in most sample size scenarios.

Antibodies associated with heparin-induced thrombocytopenia (HIT) inhibit activated protein C generation: new insights into the prothrombotic nature of HIT.

PubMed

Kowalska, M Anna; Krishnaswamy, Sriram; Rauova, Lubica; Zhai, Li; Hayes, Vincent; Amirikian, Karine; Esko, Jeffrey D; Bougie, Daniel W; Aster, Richard H; Cines, Douglas B; Poncz, Mortimer

2011-09-08

Heparin-induced thrombocytopenia (HIT) is caused by antibodies that recognize complexes between platelet factor 4 (PF4) and heparin or glycosaminoglycan side chains. These antibodies can lead to a limb- and life-threatening prothrombotic state. We now show that HIT antibodies are able to inhibit generation of activated protein C (aPC) by thrombin/thrombomodulin (IIa/TM) in the presence of PF4. Tetrameric PF4 potentiates aPC generation by formation of complexes with chondroitin sulfate (CS) on TM. Formation of these complexes occurs at a specific molar ratio of PF4 to glycosaminoglycan. This observation and the finding that the effect of heparin on aPC generation depends on the concentration of PF4 suggest similarity between PF4/CS complexes and those that bind HIT antibodies. HIT antibodies reduced the ability of PF4 to augment aPC formation. Cationic protamine sulfate, which forms similar complexes with heparin, also enhanced aPC generation, but its activity was not blocked by HIT antibodies. Our studies provide evidence that complexes formed between PF4 and TM's CS may play a physiologic role in potentiating aPC generation. Recognition of these complexes by HIT antibodies reverses the PF4-dependent enhancement in aPC generation and may contribute to the prothrombotic nature of HIT.

Neutralization of Plasmodium falciparum merozoites by antibodies against PfRH5

PubMed Central

Douglas, Alexander D.; Williams, Andrew R.; Knuepfer, Ellen; Illingworth, Joseph J.; Furze, Julie M.; Crosnier, Cécile; Choudhary, Prateek; Bustamante, Leyla Y.; Zakutansky, Sara E.; Awuah, Dennis K.; Alanine, Daniel G. W.; Theron, Michel; Worth, Andrew; Shimkets, Richard; Rayner, Julian C.; Holder, Anthony A.; Wright, Gavin J.; Draper, Simon J.

2013-01-01

There is intense interest in induction and characterization of strain-transcending neutralizing antibody against antigenically variable human pathogens. We have recently identified the human malaria parasite Plasmodium falciparum reticulocyte-binding protein homologue 5 (PfRH5) as a target of broadly-neutralizing antibodies, but there is little information regarding the functional mechanism(s) of antibody-mediated neutralization. Here, we report that vaccine-induced polyclonal anti-PfRH5 antibodies inhibit the tight attachment of merozoites to erythrocytes, and are capable of blocking the interaction of PfRH5 with its receptor basigin. Furthermore, by developing anti-PfRH5 monoclonal antibodies (mAbs), we provide evidence that i) the ability to block the PfRH5-basigin interaction in vitro is predictive of functional activity, but absence of blockade does not predict absence of functional activity; ii) neutralizing mAbs bind spatially-related epitopes on the folded protein, involving at least two defined regions of the PfRH5 primary sequence; iii) a brief exposure window of PfRH5 is likely to necessitate rapid binding of antibody to neutralize parasites; and iv) intact bivalent IgG contributes to but is not necessary for parasite neutralization. These data provide important insight into the mechanisms of broadly-neutralizing anti-malaria antibodies and further encourage anti-PfRH5 based malaria prevention efforts. PMID:24293631

Structure and anticoagulant property of a sulfated polysaccharide isolated from the green seaweed Monostroma angicava.

PubMed

Li, Na; Liu, Xue; He, Xiaoxi; Wang, Shuyao; Cao, Sujian; Xia, Zheng; Xian, Huali; Qin, Ling; Mao, Wenjun

2017-03-01

An anticoagulant-active polysaccharide PF2 was extracted with boiling water from the green seaweed Monostroma angicava, further purified by anion-exchange and size-exclusion chromatography. PF2 was a rhamnan-type sulfated polysaccharide with molecular weight of about 88.1kDa. Results of chemical and spectroscopic analyses demonstrated that PF2 consisted of→3)-α-l-Rhap-(1→ and →2)-α-l-Rhap-(1→residues, with partially branches at C-2 of→3)-α-l-Rhap-(1→residues. Sulfate groups were substituted at C-3 of →2)-α-l-Rhap-(1→ residues. The sulfated polysaccharide PF2 had a high anticoagulant action, and the mechanism of anticoagulant activity mediated by PF2 was mainly attributed to strong potentiation thrombin by heparin cofactor II. PF2 also exhibited weak effect on antithrombin-dependent thrombin or factor Xa inhibition. The fibrin(ogen)olytic activity and thrombolytic activity of PF2 were also evaluated. The investigation revealed that PF2 was a novel sulfated rhamnan differing from previously described sulfated polysaccharides from green seaweed and could be a potential anticoagulant polysaccharide. Copyright © 2016 Elsevier Ltd. All rights reserved.

Paeoniflorin protects against ischemia-induced brain damages in rats via inhibiting MAPKs/NF-κB-mediated inflammatory responses.

PubMed

Guo, Ruo-Bing; Wang, Guo-Feng; Zhao, An-Peng; Gu, Jun; Sun, Xiu-Lan; Hu, Gang

2012-01-01

Paeoniflorin (PF), the principal component of Paeoniae Radix prescribed in traditional Chinese medicine, has been reported to exhibit many pharmacological effects including protection against ischemic injury. However, the mechanisms underlying the protective effects of PF on cerebral ischemia are still under investigation. The present study showed that PF treatment for 14 days could significantly inhibit transient middle cerebral artery occlusion (MCAO)-induced over-activation of astrocytes and microglia, and prevented up-regulations of pro-inflamamtory mediators (TNFα, IL-1β, iNOS, COX(2) and 5-LOX) in plasma and brain. Further study demonstrated that chronic treatment with PF suppressed the activations of JNK and p38 MAPK, but enhanced ERK activation. And PF could reverse ischemia-induced activation of NF-κB signaling pathway. Moreover, our in vitro study revealed that PF treatment protected against TNFα-induced cell apoptosis and neuronal loss. Taken together, the present study demonstrates that PF produces a delayed protection in the ischemia-injured rats via inhibiting MAPKs/NF-κB mediated peripheral and cerebral inflammatory response. Our study reveals that PF might be a potential neuroprotective agent for stroke.

Massive remobilization of permafrost carbon during post-glacial warming

PubMed Central

Tesi, T.; Muschitiello, F.; Smittenberg, R. H.; Jakobsson, M.; Vonk, J. E.; Hill, P.; Andersson, A.; Kirchner, N.; Noormets, R.; Dudarev, O.; Semiletov, I.; Gustafsson, Ö

2016-01-01

Recent hypotheses, based on atmospheric records and models, suggest that permafrost carbon (PF-C) accumulated during the last glaciation may have been an important source for the atmospheric CO2 rise during post-glacial warming. However, direct physical indications for such PF-C release have so far been absent. Here we use the Laptev Sea (Arctic Ocean) as an archive to investigate PF-C destabilization during the last glacial–interglacial period. Our results show evidence for massive supply of PF-C from Siberian soils as a result of severe active layer deepening in response to the warming. Thawing of PF-C must also have brought about an enhanced organic matter respiration and, thus, these findings suggest that PF-C may indeed have been an important source of CO2 across the extensive permafrost domain. The results challenge current paradigms on the post-glacial CO2 rise and, at the same time, serve as a harbinger for possible consequences of the present-day warming of PF-C soils. PMID:27897191

Massive remobilization of permafrost carbon during post-glacial warming

NASA Astrophysics Data System (ADS)

Tesi, T.; Muschitiello, F.; Smittenberg, R. H.; Jakobsson, M.; Vonk, J. E.; Hill, P.; Andersson, A.; Kirchner, N.; Noormets, R.; Dudarev, O.; Semiletov, I.; Gustafsson, Ö.

2016-11-01

Recent hypotheses, based on atmospheric records and models, suggest that permafrost carbon (PF-C) accumulated during the last glaciation may have been an important source for the atmospheric CO2 rise during post-glacial warming. However, direct physical indications for such PF-C release have so far been absent. Here we use the Laptev Sea (Arctic Ocean) as an archive to investigate PF-C destabilization during the last glacial-interglacial period. Our results show evidence for massive supply of PF-C from Siberian soils as a result of severe active layer deepening in response to the warming. Thawing of PF-C must also have brought about an enhanced organic matter respiration and, thus, these findings suggest that PF-C may indeed have been an important source of CO2 across the extensive permafrost domain. The results challenge current paradigms on the post-glacial CO2 rise and, at the same time, serve as a harbinger for possible consequences of the present-day warming of PF-C soils.

Evidence of C-F-P and aromatic π-F-P weak interactions in imidazolium ionic liquids and its consequences

NASA Astrophysics Data System (ADS)

Panja, Sumit Kumar; Srivastava, Nitin; Srivastava, Jyoti; Prasad, Namburi Eswara; Noothalapati, Hemanth; Shigeto, Shinsuke; Saha, Satyen

2018-04-01

A simple change from alkyl group to alkene in side chain of imidazolium cation with same anion resulted in a drastic impact on physical properties (e.g., melting point) from bmimPF6 IL to cmimPF6 IL. The underlying reasons have been elucidated by structural and interaction studies with the help of DSC, SCXRD, vibrational and multi-nuclear NMR spectroscopic techniques. Experiments reveal existence of new weak interactions involving the carbon and π cloud of the imidazolium aromatic ring with fluoride of PF6 anion (i.e., C2-F-P and π-F-P) in cmimPF6 but are absent in structurally similar prototype IL, bmimPF6. Though weak, these interactions helped to form ladder type supramolecular arrangement, resulting in quite high melting point for cmimPF6 IL compared to bmimPF6 IL. These findings emphasize that an IL system can behave uniquely because of the existence of uncommon weak interactions.

About PF

MedlinePlus

... vapors that can cause PF (such as asbestos, coal, silica, and others) Some MEDICATIONS can cause PF. ... wide variety of inorganic dusts, including asbestos, silica, coal dust, beryllium, and hard metal dusts. Are there ...

Pfhrp2 and pfhrp3 polymorphisms in Plasmodium falciparum isolates from Dakar, Senegal: impact on rapid malaria diagnostic tests

PubMed Central

2013-01-01

Background An accurate diagnosis is essential for the rapid and appropriate treatment of malaria. The accuracy of the histidine-rich protein 2 (PfHRP2)-based rapid diagnostic test (RDT) Palutop+4® was assessed here. One possible factor contributing to the failure to detect malaria by this test is the diversity of the parasite PfHRP2 antigens. Methods PfHRP2 detection with the Palutop+4® RDT was carried out. The pfhrp2 and pfhrp3 genes were amplified and sequenced from 136 isolates of Plasmodium falciparum that were collected in Dakar, Senegal from 2009 to 2011. The DNA sequences were determined and statistical analyses of the variation observed between these two genes were conducted. The potential impact of PfHRP2 and PfHRP3 sequence variation on malaria diagnosis was examined. Results Seven P. falciparum isolates (5.9% of the total isolates, regardless of the parasitaemia; 10.7% of the isolates with parasitaemia ≤0.005% or ≤250 parasites/μl) were undetected by the PfHRP2 Palutop+4® RDT. Low parasite density is not sufficient to explain the PfHRP2 detection failure. Three of these seven samples showed pfhrp2 deletion (2.4%). The pfhrp3 gene was deleted in 12.8%. Of the 122 PfHRP2 sequences, 120 unique sequences were identified. Of the 109 PfHRP3 sequences, 64 unique sequences were identified. Using the Baker’s regression model, at least 7.4% of the P. falciparum isolates in Dakar were likely to be undetected by PfHRP2 at a parasite density of ≤250 parasites/μl (slightly lower than the evaluated prevalence of 10.7%). This predictive prevalence increased significantly between 2009 and 2011 (P = 0.0046). Conclusion In the present work, 10.7% of the isolates with a parasitaemia ≤0.005% (≤250 parasites/μl) were undetected by the PfHRP2 Palutop+4® RDT (7.4% by the predictive Baker’model). In addition, all of the parasites with pfhrp2 deletion (2.4% of the total samples) and 2.1% of the parasites with parasitaemia >0.005% and presence of pfhrp2 were not detected by PfHRP2 RDT. PfHRP2 is highly polymorphic in Senegal. Efforts should be made to more accurately determine the prevalence of non-sensitive parasites to pfHRP2. PMID:23347727

Temporal and Spatial Patterns of Preferential Flow Occurrence in the Shale Hills Catchment: From the Hillslope to the Catchment Scales

NASA Astrophysics Data System (ADS)

Liu, H.; Lin, H.

2013-12-01

Understanding temporal and spatial patterns of preferential flow (PF) occurrence is important in revealing hillslope and catchment hydrologic and biogeochemical processes. Quantitative assessment of the frequency and control of PF occurrence in the field, however, has been limited, especially at the landscape scale of hillslope and catchment. By using 5.5-years' (2007-2012) real-time soil moisture at 10 sites response to 323 precipitation events, we tested the temporal consistency of PF occurrence at the hillslope scale in the forested Shale Hills Catchment; and by using 25 additional sites with at least 1-year data (2011-2012), we evaluated the spatial patterns of PF occurrence across the catchment. To explore the potential effects of PF occurrence on catchment hydrology, wavelet analysis was performed on the recorded time series of hydrological signals (i.e., precipitation, soil moisture, catchment discharge). Considerable temporal consistence was observed in both the frequency and the main controls of PF occurrence at the hillslope scale, which was attributed largely to the statistical stability of precipitation pattern over the monitoring period and the relatively stable subsurface preferential pathways. Preferential flow tended to occur more often in response to intense rainfall events, and favored the conditions at dry hilltop or wet valley floor sites. When upscaling to the entire catchment, topographic control on the PF occurrence was amplified remarkably, leading to the identification of a subsurface PF network in the catchment. Higher frequency of PF occurrence was observed at the valley floor (average 48%), hilltop (average 46%), and swales/hillslopes near the stream (average 40%), while the hillslopes in the eastern part of the catchment were least likely to experience PF (0-20%). No clear relationship, however, was observed between terrain attributes and PF occurrence, because the initiation and persistency of PF in this catchment was controlled jointly by complex interactions among landform units, soil types, initial soil moisture, precipitation features, and season. Through the wavelet method (coherence spectrum and phase differences), dual-pore filtering effects of soil system were proven, rendering it possible to further infer characteristic properties of the underlying hydrological processes in the subsurface. We found that preferential flow dominates the catchment discharge response at short-time periods (< 3 days), while the matrix flow may dominate the discharge response at the time scales of around 10-12 days. The temporal and spatial patterns of PF occurrence revealed in this study can help advance the modeling and prediction of complex PF dynamics in this and other similar landscapes.

Metal complexes of fluorophosphines. 13. Reaction of fac-(CH/sub 3/CN)/sub 3/Mo(CO)/sub 3/ with (methylamino)bis(difluorophosphine). X-ray crystal structure analysis of a novel binuclear molybdenum fluorophosphine carbonyl complex with a bridging chlorine atom: (CO)/sub 2/Mo(/sup +/-CH/sub 3/N(PF/sub 2/)/sub 2/)/sub 2/(. mu. -PF/sub 2/)(. mu. -Cl)Mo(CO)(PF/sub 2/NHCH/sub 3/)

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

King, R.B.; Shimura, M.; Brown, G.M.

1984-01-01

Reaction of fac-(CH/sub 3/CN)/sub 3/Mo(CO)/sub 3/ with CH/sub 3/N(PF/sub 2/)/sub 2/ in acetonitrile solution at room temperature gives white, volatile, crystalline fac-(CH/sub 3/N(PF/sub 2/)/sub 2/)/sub 2/Mo(CO)/sub 3/, containing one monodentate and one bidentate CH/sub 3/N(PF/sub 2/)/sub 2/ ligand. The same reactants in boiling acetonitrile give yellow (CH/sub 3/N(PF/sub 2/)/sub 2/)/sub 4/Mo/sub 2/(CO)/sub 3/ in considerably better yield than the previously reported preparation of this binuclear complex from the cycloheptatriene complex C/sub 7/H/sub 8/Mo(CO)/sub 3/ and CH/sub 3/N(PF/sub 2/)/sub 2/ in boiling methylcyclohexane. Reaction in acetonitrile solution of fac-(CH/sub 3/CN)/sub 3/Mo(CO)/sub 3/ with CH/sub 3/N(PF/sub 2/)/sub 2/ containing about 0.2% HClmore » gives brown-red, volatile (CO)/sub 2/Mo(/sup +/-CH/sub 3/N(PF/sub 2/)/sub 2/)/sub 2/(..mu..-PF/sub 2/)(..mu..-Cl)-Mo(CO)(PF/sub 2/NHCH/sub 3/), whose composition and structure were established by single-crystal X-ray structure analysis. This novel quadruply bridged binuclear complex is obtained in considerably better yield from the reaction of (CH/sub 3/N(PF/sub 2/)/sub 2/)/sub 3/Mo/sub 2/(CO)/sub 5/ with ((C/sub 2/H/sub 5/)/sub 3/NH)Cl in acetonitirle solution. The complex has a Mo-Mo bond 2.975 A in length. Crystal data: monoclinic, space group P2/sub 1//c, a = 17.546 (4) A, b = 9.725 (2) A, c = 14.558 (3), ..beta.. = 107.20 (2)/sup 0/, Z = 4. 30 references, 2 figures, 3 tables.« less

Resting State and Elementary Steps of the Coupling of Aryl Halides with Thiols Catalyzed by Alkylbisphosphine Complexes of Palladium

PubMed Central

Alvaro, Elsa

2010-01-01

Detailed mechanistic studies on the coupling of aryl halides with thiols catalyzed by palladium complexes of the alkylbisphosphine ligand CyPF-tBu (1-dicyclohexylphosphino-2-di-tert-butylphosphinoethylferrocene) are reported. The elementary steps that constitute the catalytic cycle, i.e. oxidative addition, transmetalation and reductive elimination, have been studied, and their relative rates are reported. Each of the steps of the catalytic process occurs at temperatures that are much lower than those required for the reactions catalyzed by a combination of palladium precursors and CyPF-tBu. To explain these differences in rates between the catalytic and stoichiometric reactions, studies were conducted to identify the resting state of the catalyst of the reactions catalyzed by a combination of Pd(OAc)2 and CyPF-tBu, a combination of Pd(dba)2 and CyPF-tBu, or the likely intermediate Pd(CyPF-tBu)(Ar)(Br). These show that the major palladium complex in each case lies off of the catalytic cycle. The resting state of the reactions catalyzed by Pd(OAc)2 and CyPF-tBu was the palladium bis-thiolate complex [Pd(CyPF-tBu)(SR)2] (R = alkyl or aryl). The resting state in reactions catalyzed by Pd2(dba)3 and CyPF-tBu was the binuclear complex [Pd(CyPF-tBu)]2(μ2, η2-dba) (9). The resting state of reactions of both aromatic and aliphatic thiols catalyzed by [Pd(CyPF-tBu)(p-tolyl)(Br)] (3a) was the hydridopalladium thiolate complex [Pd(CyPF-tBu)(H)(SR)] (R= alkyl and aryl). All these palladium species have been prepared independently, and the mechanisms by which they enter the catalytic cycle have been examined in detail. These features of the reaction catalyzed by palladium and CyPF-tBu have been compared with those of reactions catalyzed by the alkylbisphosphine DiPPF and Pd(OAc)2 or Pd(dba)2. Our data indicate that the resting states of these reactions are similar to each other and that our mechanistic conclusions about reactions catalyzed by palladium and CyPF-tBu can be extrapolated to reactions catalyzed by complexes of other electron-rich bisphosphines. PMID:19453106

Identification of the platelet-derived chemokine CXCL4/PF-4 as a broad-spectrum HIV-1 inhibitor

PubMed Central

Auerbach, David J.; Lin, Yin; Miao, Huiyi; Cimbro, Raffaello; DiFiore, Michelle J.; Gianolini, Monica E.; Furci, Lucinda; Biswas, Priscilla; Fauci, Anthony S.; Lusso, Paolo

2012-01-01

The natural history of HIV-1 infection is highly variable in different individuals, spanning from a rapidly progressive course to a long-term asymptomatic infection. A major determinant of the pace of disease progression is the in vivo level of HIV-1 replication, which is regulated by a complex network of cytokines and chemokines expressed by immune and inflammatory cells. The chemokine system is critically involved in the control of HIV-1 replication by virtue of the role played by specific chemokine receptors, most notably CCR5 and CXCR4, as cell-surface coreceptors for HIV-1 entry; hence, the chemokines that naturally bind such coreceptors act as endogenous inhibitors of HIV-1. Here, we show that the CXC chemokine CXCL4 (PF-4), the most abundant protein contained within the α-granules of platelets, is a broad-spectrum inhibitor of HIV-1 infection. Unlike other known HIV-suppressive chemokines, CXCL4 inhibits infection by the majority of primary HIV-1 isolates regardless of their coreceptor-usage phenotype or genetic subtype. Consistent with the lack of viral phenotype specificity, blockade of HIV-1 infection occurs at the level of virus attachment and entry via a unique mechanism that involves direct interaction of CXCL4 with the major viral envelope glycoprotein, gp120. The binding site for CXCL4 was mapped to a region of the gp120 outer domain proximal to the CD4-binding site. The identification of a platelet-derived chemokine as an endogenous antiviral factor may have relevance for the pathogenesis and treatment of HIV-1 infection. PMID:22645343

Identification of the platelet-derived chemokine CXCL4/PF-4 as a broad-spectrum HIV-1 inhibitor.

PubMed

Auerbach, David J; Lin, Yin; Miao, Huiyi; Cimbro, Raffaello; Difiore, Michelle J; Gianolini, Monica E; Furci, Lucinda; Biswas, Priscilla; Fauci, Anthony S; Lusso, Paolo

2012-06-12

The natural history of HIV-1 infection is highly variable in different individuals, spanning from a rapidly progressive course to a long-term asymptomatic infection. A major determinant of the pace of disease progression is the in vivo level of HIV-1 replication, which is regulated by a complex network of cytokines and chemokines expressed by immune and inflammatory cells. The chemokine system is critically involved in the control of HIV-1 replication by virtue of the role played by specific chemokine receptors, most notably CCR5 and CXCR4, as cell-surface coreceptors for HIV-1 entry; hence, the chemokines that naturally bind such coreceptors act as endogenous inhibitors of HIV-1. Here, we show that the CXC chemokine CXCL4 (PF-4), the most abundant protein contained within the α-granules of platelets, is a broad-spectrum inhibitor of HIV-1 infection. Unlike other known HIV-suppressive chemokines, CXCL4 inhibits infection by the majority of primary HIV-1 isolates regardless of their coreceptor-usage phenotype or genetic subtype. Consistent with the lack of viral phenotype specificity, blockade of HIV-1 infection occurs at the level of virus attachment and entry via a unique mechanism that involves direct interaction of CXCL4 with the major viral envelope glycoprotein, gp120. The binding site for CXCL4 was mapped to a region of the gp120 outer domain proximal to the CD4-binding site. The identification of a platelet-derived chemokine as an endogenous antiviral factor may have relevance for the pathogenesis and treatment of HIV-1 infection.

Influence of central metalloligand geometry on electronic communication between metals: syntheses, crystal structures, MMCT properties of isomeric cyanido-bridged Fe2Ru complexes, and TDDFT calculations.

PubMed

Ma, Xiao; Lin, Chen-Sheng; Hu, Sheng-Min; Tan, Chun-Hong; Wen, Yue-Hong; Sheng, Tian-Lu; Wu, Xin-Tao

2014-06-02

To investigate how the central metalloligand geometry influences distant or vicinal metal-to-metal charge-transfer (MMCT) properties of polynuclear complexes, cis- and trans-isomeric heterotrimetallic complexes, and their one- and two-electron oxidation products, cis/trans-[Cp(dppe)Fe(II)NCRu(II)(phen)2CN-Fe(II)(dppe)Cp][PF6]2 (cis/trans-1[PF6]2), cis/trans-[Cp(dppe)Fe(II)NCRu(II)(phen)2CNFe(III)-(dppe)Cp][PF6]3 (cis/trans-1[PF6]3) and cis/trans-[Cp(dppe)Fe(III)NCRu(II)(phen)2CN-Fe(III)(dppe)Cp][PF6]4 (cis/trans-1[PF6]4) have been synthesized and characterized. Electrochemical measurements show the presence of electronic interactions between the two external Fe(II) atoms of the cis- and trans-isomeric complexes cis/trans-1[PF6]2. The electronic properties of all these complexes were studied and compared by spectroscopic techniques and TDDFT//DFT calculations. As expected, both mixed valence complexes cis/trans-1[PF6]3 exhibited different strong absorption signals in the NIR region, which should mainly be attributed to a transition from an MO that is delocalized over the Ru(II)-CN-Fe(II) subunit to a Fe(III) d orbital with some contributions from the co-ligands. Moreover, the NIR transition energy in trans-1[PF6]3 is lower than that in cis-1[PF6]3, which is related to the symmetry of their molecular orbitals on the basis of the molecular orbital analysis. Also, the electronic spectra of the two-electron oxidized complexes show that trans-1[PF6]4 possesses lower vicinal Ru(II) → Fe(III) MMCT transition energy than cis-1[PF6]4. Moreover, the assignment of MMCT transition of the oxidized products and the differences of the electronic properties between the cis and trans complexes can be well rationalized using TDDFT//DFT calculations. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Phosphorylation Determines the Calmodulin-mediated Ca2+ Response and Water Permeability of AQP0*

PubMed Central

Kalman, Katalin; Németh-Cahalan, Karin L.; Froger, Alexandrine; Hall, James E.

2008-01-01

In Xenopus oocytes, the water permeability of AQP0 (Pf) increases with removal of external calcium, an effect that is mediated by cytoplasmic calmodulin (CaM) bound to the C terminus of AQP0. To investigate the effects of serine phosphorylation on CaM-mediated Ca2+ regulation of Pf, we tested the effects of kinase activation, CaM inhibition, and a series of mutations in the C terminus CaM binding site. Calcium regulation of AQP0 Pf manifests four distinct phenotypes: Group 1, with high Pf upon removal of external Ca2+ (wild-type, S229N, R233A, S235A, S235K, K238A, and R241E); Group 2, with high Pf in elevated (5 mm) external Ca2+ (S235D and R241A); Group 3, with high Pf and no Ca2+ regulation (S229D, S231N, S231D, S235N, and S235N/I236S); and Group 4, with low Pf and no Ca2+ regulation (protein kinase A and protein kinase C activators, S229D/S235D and S235N/I236S). Within each group, we tested whether CaM binding mediates the phenotype, as shown previously for wild-type AQP0. In the presence of calmidazolium, a CaM inhibitor, S235D showed high Pf and no Ca2+ regulation, suggesting that S235D still binds CaM. Contrarily, S229D showed a decrease in recruitment of CaM, suggesting that S229D is unable to bind CaM. Taken together, our results suggest a model in which CaM acts as an inhibitor of AQP0 Pf. CaM binding is associated with a low Pf state, and a lack of CaM binding is associated with a high Pf state. Pathological conditions of inappropriate phosphorylation or calcium/CaM regulation could induce Pf changes contributing to the development of a cataract. PMID:18508773

Identification of Plasmodium falciparum reticulocyte binding protein homologue 5-interacting protein, PfRipr, as a highly conserved blood-stage malaria vaccine candidate.

PubMed

Ntege, Edward H; Arisue, Nobuko; Ito, Daisuke; Hasegawa, Tomoyuki; Palacpac, Nirianne M Q; Egwang, Thomas G; Horii, Toshihiro; Takashima, Eizo; Tsuboi, Takafumi

2016-11-04

Genetic variability in Plasmodium falciparum malaria parasites hampers current malaria vaccine development efforts. Here, we hypothesize that to address the impact of genetic variability on vaccine efficacy in clinical trials, conserved antigen targets should be selected to achieve robust host immunity across multiple falciparum strains. Therefore, suitable vaccine antigens should be assessed for levels of polymorphism and genetic diversity. Using a total of one hundred and two clinical isolates from a region of high malaria transmission in Uganda, we analyzed extent of polymorphism and genetic diversity in four recently reported novel blood-stage malaria vaccine candidate proteins: Rh5 interacting protein (PfRipr), GPI anchored micronemal antigen (PfGAMA), rhoptry-associated leucine zipper-like protein 1 (PfRALP1) and Duffy binding-like merozoite surface protein 1 (PfMSPDBL1). In addition, utilizing the wheat germ cell-free system, we expressed recombinant proteins for the four candidates based on P. falciparum laboratory strain 3D7 sequences, immunized rabbits to obtain specific antibodies (Abs) and performed functional growth inhibition assay (GIA). The GIA activity of the raised Abs was demonstrated using both homologous 3D7 and heterologous FVO strains in vitro. Both pfripr and pfralp1 are less polymorphic but the latter is comparatively more diverse, with varied number of regions having insertions and deletions, asparagine and 6-mer repeats in the coding sequences. Pfgama and pfmspdbl1 are polymorphic and genetically diverse among the isolates with antibodies against the 3D7-based recombinant PfGAMA and PfMSPDBL1 inhibiting merozoite invasion only in the 3D7 but not FVO strain. Moreover, although Abs against the 3D7-based recombinant PfRipr and PfRALP1 proteins potently inhibited merozoite invasion of both 3D7 and FVO, the GIA activity of anti-PfRipr was much higher than that of anti-PfRALP1. Thus, PfRipr is regarded as a promising blood-stage vaccine candidate for next-generation vaccines against P. falciparum. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of Opalescence(®) bleaching gels on the elution of bulk-fill composite components.

PubMed

Schuster, Lena; Reichl, Franz-Xaver; Rothmund, Lena; He, Xiuli; Yang, Yang; Van Landuyt, Kirsten L; Kehe, Kai; Polydorou, Olga; Hickel, Reinhard; Högg, Christof

2016-02-01

Bleaching treatments can affect release of components from conventional composites. In this continuing study the influence of two different bleaching gels on the elution of bulk-fill composite components was investigated. The composites Tetric EvoCeram(®) Bulk Fill, QuiXFil™ and X-tra fil were treated with the bleaching gels Opalescence PF 15% (PF 15%) for 5 h and PF 35% (PF 35%) for 30 min and then stored in methanol and water for 24 h and 7 d. The eluates were analyzed by gas chromatography/mass spectrometry (GC/MS). Unbleached specimens were used as control group. A total of 7 different elutable substances have been identified from the investigated composites after bleaching-treatment. Three of them were methacrylates: 2-hydroxyethyl methacrylate (HEMA), triethylene glycol dimethacrylate (TEGDMA) and trimethylolpropane trimethacrylate (TMPTMA). Compared to the unbleached controls an increase in elution after PF 15%-treatment of following compounds was found: HEMA (Tetric EvoCeram(®) Bulk Fill), TEGDMA (QuiXFil™, X-tra fil) and 4-N,N-dimethylaminobenzoic acid butyl ethoxy ester (DMABEE) (Tetric EvoCeram(®) Bulk Fill, QuiXFil™, X-tra fil). Following compounds showed a reduction in elution after PF 35%-treatment compared to controls: TEGDMA (QuiXFil™) and DMABEE (Tetric EvoCeram(®) Bulk Fill). The highest concentration of HEMA was 0.22 mmol/l (Tetric EvoCeram(®) Bulk Fill, methanol, 7 d, PF 15%), the highest concentration of TEGDMA was 0.3 mmol/l (X-tra fil, water, 7 d, PF 15%) and the highest concentration of DMABEE was 0.05 mmol/l (QuiXFil™, water, 7 d, PF 35%). PF 15% and PF 35% can lead to reduced and/or increased elution of some bulk-fill components, compared to unbleached bulk-fill composites. Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

An infrared and Raman study of the reorientational motions and phase transition in and structure of CsPF6

NASA Astrophysics Data System (ADS)

Heyns, Anton M.; de Waal, Danita

1992-12-01

CsPF6I is face-centered cubic and the PF6- ions are randomly distributed among the six equivalent orientations in the crystal. The ions librate in equilibrium positions for an average time τ, and also jump from one orientation to another in a time which is much shorter than τ. The six different orientations in CsPF6I are of much lower symmetry than the full molecular one. The full vibrational spectra of CsPF6 are reported over the temperature range of 300-4 K and can be analyzed in Phase I in terms of (Oh,C¯4v) where C¯4v denotes the symmetry of the ion and Oh that of the site symmetry S. The polarized Raman spectra of single crystals of CsPF6I are interpreted in terms of all the different orientations of the PF6- ions and excellent agreement is obtained between predicted and experimental results. At 90 K CsPF6 undergoes a phase transition and a crystal structure of P4/nmm-D4h7 is assigned to Phase II. This transition is of the second order and shows behavior which corresponds to those of critical phenomena. An order parameter ξ is defined and a critical constant β is calculated to be equal to 0.3. In CsPF6II two orientations of the PF6- ions exist, both conforming to 4mm-C4v symmetry and the disorder persisting in this phase causes the splitting of the vibrational bands to be fully resolved below 60 K only. An activation energy of ˜3.0 kJ/mol is calculated for the motions of the PF6- ions between 90 and 60 K from the variation of the linewidths and intensities of vibrational bands.

Insights into the epidemiological link between biting flies and pemphigus foliaceus in southeastern Brazil.

PubMed

Vernal, Sebastian; Pepinelli, Mateus; Casanova, Claudio; Goulart, Thais M; Kim, Olivia; De Paula, Natalia A; Pinto, Mara C; Sá-Nunes, Anderson; Roselino, Ana Maria

2017-12-01

Black fly and sandfly bites are related to the endemicity of pemphigus foliaceus (PF); however, an immune reaction against the salivary proteins from these flies still requires confirmation in the case of PF patients living in southeastern Brazil. To georeference the distribution of Simuliidae (Diptera: Simuliidae) and Phlebotominae (Diptera: Psychodidae) and of PF cases in the northeastern region of São Paulo State, and to assess the humoral immune response against salivary gland extracts (SGEs) from biting flies in PF patients, relatives, and neighbours. PF patients' medical information recorded between 1965 and 2014 were obtained from the database of the University Hospital. Data on the distribution of fly species were collected from scientific reports and epidemiological databases. Spatial maps relating the distribution of biting flies with PF cases were plotted. Serum IgG antibodies against the SGEs from Simulium nigrimanum, Nyssomyia neivai, and Aedes aegypti (as control) were determined by ELISA. Two hundred and eighty-five PF cases were distributed in 60 municipalities with a prevalence of 57.5 per million inhabitants, revealing well-defined geographical clusters. S. nigrimanum and N. neivai specimens were registered in eight (13.3%) and 26 (43.3%) of these municipalities, respectively. PF patients, and their relatives presented higher levels of IgG against the SGEs of S. nigrimanum and N. neivai (P<0.001 for both), but not against the SGE from A. aegypti (P=0.115 and P=0.552, respectively), as compared to controls. IgG against the SGEs from S. nigrimanum and N. neivai but not against the SGE from A. aegypti correlated with levels of anti-Desmoglein 1 in PF patients (r=0.3848, P=0.039; and r=0.416, P=0.022, respectively). An epidemiological link between biting flies and PF in southeastern Brazil is proposed, implying a possible role of the salivary proteins from these flies in PF etiopathogenesis. Copyright © 2017 Elsevier B.V. All rights reserved.

Elevated Peak Postoperative B-type Natriuretic Peptide Predicts Decreased Longer-Term Physical Function after Primary Coronary Artery Bypass Graft Surgery

PubMed Central

Fox, Amanda A.; Marcantonio, Edward R.; Collard, Charles D.; Thoma, Mathis; Perry, Tjorvi E.; Shernan, Stanton K.; Muehlschlegel, Jochen D.; Body, Simon C.

2011-01-01

Background Elevated peak postoperative B-type natriuretic peptide (BNP) is associated with increased major adverse cardiovascular events and all-cause mortality after coronary artery bypass graft (CABG) surgery. Whether elevated postoperative BNP predicts worse post-discharge physical function (PF) is unknown. We hypothesized that peak postoperative BNP associates with PF assessed up to 2 years after CABG surgery, even after adjusting for clinical risk factors including preoperative PF. Methods This two institution prospective cohort study included patients undergoing primary CABG surgery with cardiopulmonary bypass. Short Form-36 questionnaires were administered to subjects preoperatively and 6 months, 1 and 2 years postoperatively. Short Form-36 PF domain scores were calculated using the Short Form-36 norm based scoring algorithm. Plasma BNP concentrations measured preoperatively and on postoperative days 1–5 were log10 transformed before analysis. To determine whether peak postoperative BNP independently predicts PF scores 6 months through 2 years after CABG surgery, multivariable longitudinal regression analysis of the postoperative PF scores was performed, adjusting for important clinical risk factors. Results 845 subjects (mean age±SD: 65±10 years) were analyzed. Peak postoperative BNP was significantly associated with postoperative PF (effect estimate for log10 peak BNP = −7.66 PF score points; 95% CI = −9.68, −5.64; P=<0.0001). After multivariable adjustments, peak postoperative BNP remained independently associated with postoperative PF (effect estimate for log10 peak BNP =−3.06 PF score points; 95% CI = −5.15, −0.97; P=0.004). Conclusions Elevated peak postoperative BNP independently associates with worse longer-term physical function after primary CABG surgery. Future studies are needed to determine whether medical management targeted towards reducing elevated postoperative BNP can improve PF after CABG surgery. PMID:21427536

Modifications of Geometric Truncation of the Scattering Phase Function

NASA Astrophysics Data System (ADS)

Radkevich, A.

2017-12-01

Phase function (PF) of light scattering on large atmospheric particles has very strong peak in forward direction constituting a challenge for accurate numerical calculations of radiance. Such accurate (and fast) evaluations are important in the problems of remote sensing of the atmosphere. Scaling transformation replaces original PF with a sum of the delta function and a new regular smooth PF. A number of methods to construct such a PF were suggested. Delta-M and delta-fit methods require evaluation of the PF moments which imposes a numerical problem if strongly anisotropic PF is given as a function of angle. Geometric truncation keeps the original PF unchanged outside the forward peak cone replacing it with a constant within the cone. This approach is designed to preserve the asymmetry parameter. It has two disadvantages: 1) PF has discontinuity at the cone; 2) the choice of the cone is subjective, no recommendations were provided on the choice of the truncation angle. This choice affects both truncation fraction and the value of the phase function within the forward cone. Both issues are addressed in this study. A simple functional form of the replacement PF is suggested. This functional form allows for a number of modifications. This study consider 3 versions providing continuous PF. The considered modifications also bear either of three properties: preserve asymmetry parameter, provide continuity of the 1st derivative of the PF, and preserve mean scattering angle. The second problem mentioned above is addressed with a heuristic approach providing unambiguous criterion of selection of the truncation angle. The approach showed good performance on liquid water and ice clouds with different particle size distributions. Suggested modifications were tested on different cloud PFs using both discrete ordinates and Monte Carlo methods. It was showed that the modifications provide better accuracy of the radiance computation compare to the original geometric truncation.

Penile fracture epidemiology, diagnosis and management in Iran: a narrative review

PubMed Central

Mirzazadeh, Majid; Fallahkarkan, Morteza

2017-01-01

Penile fracture (PF) is considered an emergency in urology. In the literature there are some case series reporting considerable incidence of PF in some parts of Iran. There are no accurate data about the incidence of PF all around Iran. Although it may be uncommon in other parts of the country and in the other countries, it can also be underreported. There are some challenges in diagnosis, management, and also reporting of these cases. In this review of Iranian medical literature, we searched for penile fracture and penile injury keywords in Medline, Scopus, SID, Google and Persian medical journals. We reviewed the status of epidemiology, etiology, diagnosis, management and complications of PF in different parts of Iran in the published literature. To collect more accurate data, we also performed a questionnaire-based study with sending questionnaires by emails to 700 urologists throughout the country with 14% response rate. Incidence of PF varies significantly in different parts of Iran. Western province of Kermanshah has a significantly higher rate of PF. Adding data from different regions of Iran, we calculated that incidence of PF in Iran can be estimated between 1.14 to 10.48 per 100,000 of male populations, most probably closer to lower end. Although the incidence of PF varies significantly in different geographical areas, urologists practicing in Iran on average may encounter a PF patient every 3.5 months. To diagnose PF, majority of reviewed studies relied on history and clinical examination and did not recommend imaging except in patients with possible urethral injuries. Immediate surgical intervention can make good functional results with low morbidity and short hospital stay. Delayed surgical intervention and observational management approaches need large population studies with long term follow up. PMID:28540222

Penile fracture epidemiology, diagnosis and management in Iran: a narrative review.

PubMed

Mirzazadeh, Majid; Fallahkarkan, Morteza; Hosseini, Jalil

2017-04-01

Penile fracture (PF) is considered an emergency in urology. In the literature there are some case series reporting considerable incidence of PF in some parts of Iran. There are no accurate data about the incidence of PF all around Iran. Although it may be uncommon in other parts of the country and in the other countries, it can also be underreported. There are some challenges in diagnosis, management, and also reporting of these cases. In this review of Iranian medical literature, we searched for penile fracture and penile injury keywords in Medline, Scopus, SID, Google and Persian medical journals. We reviewed the status of epidemiology, etiology, diagnosis, management and complications of PF in different parts of Iran in the published literature. To collect more accurate data, we also performed a questionnaire-based study with sending questionnaires by emails to 700 urologists throughout the country with 14% response rate. Incidence of PF varies significantly in different parts of Iran. Western province of Kermanshah has a significantly higher rate of PF. Adding data from different regions of Iran, we calculated that incidence of PF in Iran can be estimated between 1.14 to 10.48 per 100,000 of male populations, most probably closer to lower end. Although the incidence of PF varies significantly in different geographical areas, urologists practicing in Iran on average may encounter a PF patient every 3.5 months. To diagnose PF, majority of reviewed studies relied on history and clinical examination and did not recommend imaging except in patients with possible urethral injuries. Immediate surgical intervention can make good functional results with low morbidity and short hospital stay. Delayed surgical intervention and observational management approaches need large population studies with long term follow up.

A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria

PubMed Central

Mbengue, Alassane; Bhattacharjee, Souvik; Pandharkar, Trupti; Liu, Haining; Estiu, Guillermina; Stahelin, Robert V.; Rizk, Shahir; Njimoh, Dieudonne L.; Ryan, Yana; Chotivanich, Kesinee; Nguon, Chea; Ghorbal, Mehdi; Lopez-Rubio, Jose-Juan; Pfrender, Michael; Emrich, Scott; Mohandas, Narla; Dondorp, Arjen M.; Wiest, Olaf; Haldar, Kasturi

2015-01-01

Artemisinins are the corner stone of anti-malarial drugs1. Emergence and spread of resistance to them2–4 raises risk of wiping out recent gains achieved in reducing world-wide malaria burden and threatens future malaria control and elimination on a global level. Genome wide association studies (GWAS) have revealed parasite genetic loci associated with artemisinin resistance5–10. However, there is no consensus on biochemical targets of artemisinin. Whether and how these targets interact with genes identified by GWAS, remains unknown. Here we provide biochemical and cellular evidence that artemisinins are potent inhibitors of Plasmodium falciparum phosphatidylinositol-3-kinase (PfPI3K), revealing an unexpected mechanism of action. In resistant clinical strains, increased PfPI3K was associated with the C580Y mutation in P. falciparum Kelch13 (PfKelch13), a primary marker of artemisinin resistance. Polyubiquitination of PfPI3K and its binding to PfKelch13 were reduced by PfKelch13 mutation, which limited proteolysis of PfPI3K and thus increased levels of the kinase as well as its lipid product phosphatidylinositol 3-phosphate (PI3P). We find PI3P levels to be predictive of artemisinin resistance in both clinical and engineered laboratory parasites as well as across non-isogenic strains. Elevated PI3P induced artemisinin resistance in absence of PfKelch13 mutations, but remained responsive to regulation by PfKelch13. Evidence is presented for PI3P-dependent signaling, where transgenic expression of an additional kinase confers resistance. Together these data present PI3P as the key mediator of artemisinin resistance and the sole PfPI3K as an important target for malaria elimination. PMID:25874676

A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria.

PubMed

Mbengue, Alassane; Bhattacharjee, Souvik; Pandharkar, Trupti; Liu, Haining; Estiu, Guillermina; Stahelin, Robert V; Rizk, Shahir S; Njimoh, Dieudonne L; Ryan, Yana; Chotivanich, Kesinee; Nguon, Chea; Ghorbal, Mehdi; Lopez-Rubio, Jose-Juan; Pfrender, Michael; Emrich, Scott; Mohandas, Narla; Dondorp, Arjen M; Wiest, Olaf; Haldar, Kasturi

2015-04-30

Artemisinins are the cornerstone of anti-malarial drugs. Emergence and spread of resistance to them raises risk of wiping out recent gains achieved in reducing worldwide malaria burden and threatens future malaria control and elimination on a global level. Genome-wide association studies (GWAS) have revealed parasite genetic loci associated with artemisinin resistance. However, there is no consensus on biochemical targets of artemisinin. Whether and how these targets interact with genes identified by GWAS, remains unknown. Here we provide biochemical and cellular evidence that artemisinins are potent inhibitors of Plasmodium falciparum phosphatidylinositol-3-kinase (PfPI3K), revealing an unexpected mechanism of action. In resistant clinical strains, increased PfPI3K was associated with the C580Y mutation in P. falciparum Kelch13 (PfKelch13), a primary marker of artemisinin resistance. Polyubiquitination of PfPI3K and its binding to PfKelch13 were reduced by the PfKelch13 mutation, which limited proteolysis of PfPI3K and thus increased levels of the kinase, as well as its lipid product phosphatidylinositol-3-phosphate (PI3P). We find PI3P levels to be predictive of artemisinin resistance in both clinical and engineered laboratory parasites as well as across non-isogenic strains. Elevated PI3P induced artemisinin resistance in absence of PfKelch13 mutations, but remained responsive to regulation by PfKelch13. Evidence is presented for PI3P-dependent signalling in which transgenic expression of an additional kinase confers resistance. Together these data present PI3P as the key mediator of artemisinin resistance and the sole PfPI3K as an important target for malaria elimination.

Malaria Parasite-Infected Erythrocytes Secrete PfCK1, the Plasmodium Homologue of the Pleiotropic Protein Kinase Casein Kinase 1

PubMed Central

Dorin-Semblat, Dominique; Demarta-Gatsi, Claudia; Hamelin, Romain; Armand, Florence; Carvalho, Teresa Gil; Moniatte, Marc; Doerig, Christian

2015-01-01

Casein kinase 1 (CK1) is a pleiotropic protein kinase implicated in several fundamental processes of eukaryotic cell biology. Plasmodium falciparum encodes a single CK1 isoform, PfCK1, that is expressed at all stages of the parasite’s life cycle. We have previously shown that the pfck1 gene cannot be disrupted, but that the locus can be modified if no loss-of-function is incurred, suggesting an important role for this kinase in intra-erythrocytic asexual proliferation. Here, we report on the use of parasite lines expressing GFP- or His-tagged PfCK1 from the endogenous locus to investigate (i) the dynamics of PfCK1 localisation during the asexual cycle in red blood cells, and (ii) potential interactors of PfCK1, so as to gain insight into the involvement of the enzyme in specific cellular processes. Immunofluorescence analysis reveals a dynamic localisation of PfCK1, with evidence for a pool of the enzyme being directed to the membrane of the host erythrocyte in the early stages of infection, followed by a predominantly intra-parasite localisation in trophozoites and schizonts and association with micronemes in merozoites. Furthermore, we present strong evidence that a pool of enzymatically active PfCK1 is secreted into the culture supernatant, demonstrating that PfCK1 is an ectokinase. Our interactome experiments and ensuing kinase assays using recombinant PfCK1 to phosphorylate putative interactors in vitro suggest an involvement of PfCK1 in many cellular processes such as mRNA splicing, protein trafficking, ribosomal, and host cell invasion. PMID:26629826

Plantarflexor weakness negatively impacts walking in persons with multiple sclerosis more than plantarflexor spasticity

PubMed Central

Wagner, Joanne M.; Kremer, Theodore R.; Van Dillen, Linda R.; Naismith, Robert T.

2014-01-01

Objective To determine if plantarflexor (PF) spasticity or ankle strength best predicts variance in walking capacity or self-perceived limitations in walking in persons with multiple sclerosis (pwMS), and if pwMS with PF spasticity are weaker and have greater walking dysfunction than pwMS without PF spasticity. Design Cross-sectional study. Setting University research laboratory. Participants Forty-two pwMS (age: 42.9 ± 10.1 years; Expanded Disability Status Scale (EDSS): median = 3.0, range = 0–6) and 14 adults without disability (WD) (age: 41.9 ± 10.1 years). Intervention Not applicable. Main Outcome Measures PF spasticity and dorsiflexion (DF) and PF maximum voluntary isometric torque (MVIT) were assessed using the Modified Ashworth Scale (MAS) and a computerized dynamometer, respectively. The Timed 25-Foot Walk Test (T25FWT) was the primary outcome measure of walking capacity. Secondary measures included the Six Minute Walk Test (6MWT) and 12-item Multiple Sclerosis Walking Scale (MSWS-12). Results PF strength was the most consistent predictor of the variance in walking capacity (T25FWT: R2 change = 0.23 to 0.29, p ≤ 0.001; 6MWT: R2 change = 0.12 to 0.29, p ≤ 0.012), and self-perceived limitations of walking (MSWS-12: R2 change = 0.04 to 0.14, p < 0.18). There were no significant differences (p > 0.05) between the pwMS with PF spasticity and pwMS without PF spasticity for any of the outcome measures. Conclusions Our study suggests a unique contribution of PF weakness to walking dysfunction in pwMS, and highlights the importance of evaluating PF strength in this clinical population. PMID:24582617

PHISTc protein family members localize to different subcellular organelles and bind Plasmodium falciparum major virulence factor PfEMP-1.

PubMed

Kumar, Vikash; Kaur, Jasweer; Singh, Amrit P; Singh, Vineeta; Bisht, Anjali; Panda, Jiban J; Mishra, Prakash C; Hora, Rachna

2018-01-01

Plasmodium falciparum encodes a novel repertoire of the Plasmodium helical interspersed subtelomeric (PHIST) family of exported proteins, which play diverse roles in infected red blood cells, contributing to malaria pathogenesis. PHIST proteins are central to parasite biology and modify human erythrocytes by interacting with parasite and host proteins. Here, we have attempted to understand the localization and function of two unexplored proteins of the PHISTc subfamily, PFD1140w and PF11_0503, and compared these with a well-characterized member, PFI1780w. We demonstrate that Phist domains assume different oligomeric states owing to a distinct array of subunit interface residues. Colocalization of a Maurer's cleft signature protein, P. falciparum skeleton-binding protein-1 (PfSBP-1), and P. falciparum erythrocyte membrane protein-1 (PfEMP-1) revealed different subcellular destinations for these PHIST members. We further show the binding of recombinant PHIST proteins to the cytoplasmic tail of PfEMP-1 and a novel interaction with PfSBP-1. Interestingly, PFD1140w interacts with PfEMP-1 and PfSBP-1 simultaneously in vitro leading to formation of a complex. These two distant PHISTc members also bind PfEMP-1 on distinct sites, despite sharing the Phist domain. Our data re-emphasize a supportive role for PHIST proteins in cytoadhesion, and identify a new binding partner, PfSBP-1, for members of this family. This information therefore adds another chapter to the understanding of P. falciparum biology and highlights the significance of the unexplored PHIST family. © 2017 Federation of European Biochemical Societies.

Plantar fascia segmentation and thickness estimation in ultrasound images.

PubMed

Boussouar, Abdelhafid; Meziane, Farid; Crofts, Gillian

2017-03-01

Ultrasound (US) imaging offers significant potential in diagnosis of plantar fascia (PF) injury and monitoring treatment. In particular US imaging has been shown to be reliable in foot and ankle assessment and offers a real-time effective imaging technique that is able to reliably confirm structural changes, such as thickening, and identify changes in the internal echo structure associated with diseased or damaged tissue. Despite the advantages of US imaging, images are difficult to interpret during medical assessment. This is partly due to the size and position of the PF in relation to the adjacent tissues. It is therefore a requirement to devise a system that allows better and easier interpretation of PF ultrasound images during diagnosis. This study proposes an automatic segmentation approach which for the first time extracts ultrasound data to estimate size across three sections of the PF (rearfoot, midfoot and forefoot). This segmentation method uses artificial neural network module (ANN) in order to classify small overlapping patches as belonging or not-belonging to the region of interest (ROI) of the PF tissue. Features ranking and selection techniques were performed as a post-processing step for features extraction to reduce the dimension and number of the extracted features. The trained ANN classifies the image overlapping patches into PF and non-PF tissue, and then it is used to segment the desired PF region. The PF thickness was calculated using two different methods: distance transformation and area-length calculation algorithms. This new approach is capable of accurately segmenting the PF region, differentiating it from surrounding tissues and estimating its thickness. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Determinant Factors of the Squat Jump in Sprinting and Jumping Athletes

PubMed Central

González-Badillo, Juan José; Jiménez-Reyes, Pedro; Ramírez-Lechuga, Jorge

2017-01-01

Abstract The aim of this study was to assess the relationship between strength variables and maximum velocity (Vmax) in the squat jump (SJ) in sprinting and jumping athletes. Thirty-two sprinting and jumping athletes of national level (25.4 ± 4.5 years; 79.4 ± 6.9 kg and 180.4 ± 6.0 cm) participated in the study. Vmax in the SJ showed significant relationships with peak force 1 (PF1) (r = 0.82, p ≤ 0.001), peak force 2 (PF2) (r = 0.68, p ≤ 0.001), PF2 by controlling for PF1 (r = 0.30, non-significant), the maximum rate of force development at peak force 1 (RFDmax1) (r = 0.62, p ≤ 0.001), mean RFD 1 (RFDmean1) (r = 0.48, p ≤ 0.01), mean RFD 2 (RFDmean2) (r = 0.70, p ≤ 0.001), force at RFDmax1 (r = 0.36, p ≤ 0.05), force at RFDmax2 (r = 0.83, p ≤ 0.001) and force at RFDmax2 by controlling for PF1 (r = 0.40, p ≤ 0.05). However, Vmax in the SJ was associated negatively with the ratio PF2/PF1 (r = -0.54, p ≤ 0.01), time at peak force 2 (Tp2) (r = -0.64, p ≤ 0.001) and maximum rate of force development at peak force 2 (RFDmax2) (r = -0.71, p ≤ 0.001). These findings indicate that the peak force achieved at the beginning of the movement (PF1) is the main predictor of performance in jumping, although the RFDmax values and the ratio PF2/PF1 are also variables to be taken into account when analyzing the determinant factors of vertical jumping. PMID:28828074

A retrospective study of antihypertensives in pemphigus: a still unchartered odyssey particularly between thiols, amides and phenols

PubMed Central

Gornowicz-Porowska, Justyna; Bowszyc-Dmochowska, Monika; Dmochowski, Marian

2015-01-01

Introduction Autoimmune pemphigus diseases comprise several entities with serious prognoses, including the pemphigus vulgaris (PV) group and pemphigus foliaceus (PF) group. Antihypertensives are suspected to be one of the factors triggering/sustaining pemphigus. Here, the data of pemphigus patients regarding arterial hypertension (AH) and taking potentially noxious drugs were statistically analyzed in a setting of a Polish university dermatology department. Material and methods Medical histories of pemphigus patients (40 admissions of 24 female patients – 13 PV, 11 PF; and 102 admissions of 38 male patients – 24 PV, 14 PF), diagnosed at both immunopathological and biochemical-molecular levels, were studied. Results Ten of 16 (62.50%) AH-positive PV patients received known PV triggers/sustainers 11 times (1–3 per patient). Fourteen of 15 (93.33%) AH-positive PF patients received known PF triggers/sustainers 21 times (1–3 per patient). No differences in numbers of patients taking potentially culprit drugs were shown between PV and PF (Fisher's exact test: p = 0.0829; Yates’ χ2 test: p = 0.1048). The most frequently used culprit drugs were ramipril in PV and enalapril in PF. On average, each PV/PF AH-positive patient received 3.161 different antihypertensives in his/her history of admissions (2.155 antihypertensives per admission). Conclusions Drug triggering should be suspected in every case of newly diagnosed or exacerbated pemphigus, as eliminating possible PV/PF triggers/sustainers may alleviate the clinical symptoms and enable the decrease of dose/range of immunosuppressants regardless of pemphigus form. Eliminating possible drug PV/PF triggers/sustainers may alleviate the clinical symptoms and enable the decrease of dose/range of immunosuppressants regardless of pemphigus form. PMID:26528346

Preferential flows and soil moistures on a Benggang slope: Determined by the water and temperature co-monitoring

NASA Astrophysics Data System (ADS)

Tao, Yu; He, Yangbo; Duan, Xiaoqian; Zou, Ziqiang; Lin, Lirong; Chen, Jiazhou

2017-10-01

Soil preferential flow (PF) has important effects on rainfall infiltration, moisture distribution, and hydrological and ecological process; but it is very difficult to monitor and characterize on a slope. In this paper, soil water and soil temperature at 20, 40, 60, 80 cm depths in six positions were simultaneously monitored at high frequency to confirm the occurrence of PF at a typical Benggang slope underlain granite residual deposits, and to determine the interaction of soil moisture distribution and Benggang erosion. In the presence of PF, the soil temperature was first (half to one hour) governed by the rainwater temperature, then (more than one hour) governed by the upper soil temperature; in the absence of PF (only matrix flow, MF), the soil temperature was initially governed by the upper soil temperature, then by the rainwater temperature. The results confirmed the water replacement phenomenon in MF, thus it can be distinguished from PF by additional temperature monitoring. It indicates that high frequency moisture and temperature monitoring can determine the occurrence of PF and reveal the soil water movement. The distribution of soil water content and PF on the different positions of the slope showed that a higher frequency of PF resulted in a higher variation of average of water content. The frequency of PF at the lower position can be three times as that of the upper position, therefore, the variation coefficient of soil water content increased from 4.67% to 12.68% at the upper position to 8.18%-33.12% at the lower position, where the Benggang erosion (soil collapse) was more possible. The results suggest strong relationships between PF, soil water variation, and collapse activation near the Benggang wall.

Sulfur mobilization for Fe-S cluster assembly by the essential SUF pathway in the Plasmodium falciparum apicoplast and its inhibition.

PubMed

Charan, Manish; Singh, Nidhi; Kumar, Bijay; Srivastava, Kumkum; Siddiqi, Mohammad Imran; Habib, Saman

2014-06-01

The plastid of the malaria parasite, the apicoplast, is essential for parasite survival. It houses several pathways of bacterial origin that are considered attractive sites for drug intervention. Among these is the sulfur mobilization (SUF) pathway of Fe-S cluster biogenesis. Although the SUF pathway is essential for apicoplast maintenance and parasite survival, there has been limited biochemical investigation of its components and inhibitors of Plasmodium SUFs have not been identified. We report the characterization of two proteins, Plasmodium falciparum SufS (PfSufS) and PfSufE, that mobilize sulfur in the first step of Fe-S cluster assembly and confirm their exclusive localization to the apicoplast. The cysteine desulfurase activity of PfSufS is greatly enhanced by PfSufE, and the PfSufS-PfSufE complex is detected in vivo. Structural modeling of the complex reveals proximal positioning of conserved cysteine residues of the two proteins that would allow sulfide transfer from the PLP (pyridoxal phosphate) cofactor-bound active site of PfSufS. Sulfide release from the l-cysteine substrate catalyzed by PfSufS is inhibited by the PLP inhibitor d-cycloserine, which forms an adduct with PfSufS-bound PLP. d-Cycloserine is also inimical to parasite growth, with a 50% inhibitory concentration close to that reported for Mycobacterium tuberculosis, against which the drug is in clinical use. Our results establish the function of two proteins that mediate sulfur mobilization, the first step in the apicoplast SUF pathway, and provide a rationale for drug design based on inactivation of the PLP cofactor of PfSufS. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

An initial psychometric evaluation of the German PROMIS v1.2 Physical Function item bank in patients with a wide range of health conditions.

PubMed

Liegl, Gregor; Rose, Matthias; Correia, Helena; Fischer, H Felix; Kanlidere, Sibel; Mierke, Annett; Obbarius, Alexander; Nolte, Sandra

2018-01-01

To translate the PROMIS Physical Function (PF) item bank version 1.2 into German and to investigate psychometric properties of resulting full bank and seven derived short forms. Cross-sectional psychometric study. Inpatient and outpatient clinics of the Department of Psychosomatic Medicine at Charité-Universitätsmedizin Berlin, Germany. A total of 10 adult patients with various chronic diseases participated in cognitive debriefing interviews. The final item bank was administered to n = 266 adult patients with a broad range of medical conditions. Patient-reported outcome assessment as part of routine care. PROMIS v1.2 PF bank; MOS SF-36 PF scale (PF-10). Cross-cultural adaptation of the item bank followed established guidelines. For the final German translation, the corrected item-total correlations ranged from 0.44 to 0.84. Cronbach's alpha was high for each PROMIS PF short form ( α = 0.88-0.96). The full PROMIS PF bank and most short forms correlated highly with the SF-36 PF-10 ( r = 0.85-0.90), with the exception of PROMIS Upper Extremity ( r = 0.64). PROMIS Upper Extremity showed ceiling effects and lower agreement with the full bank than other short forms. Unidimensionality was supported for all PROMIS PF measures using traditional factor analysis and nonparametric item response theory. The German PROMIS PF bank was found to be conceptually equivalent to the English version and fulfilled the psychometric requirements for use of short forms in clinical practice. Future studies should pay particular attention to samples with upper extremity functional limitations to further investigate the dimensional structure of PF as conceptualized according to PROMIS.

A Phase 1 study of PF-04929113 (SNX-5422), an orally bioavailable heat shock protein 90 inhibitor in patients with refractory solid tumor malignancies and lymphomas

PubMed Central

Rajan, Arun; Kelly, Ronan J.; Trepel, Jane B.; Kim, Yeong Sang; Alarcon, Sylvia V.; Kummar, Shivaani; Gutierrez, Martin; Crandon, Sonja; Zein, Wadih M.; Jain, Lokesh; Mannargudi, Baskar; Figg, William D.; Houk, Brett E.; Shnaidman, Michael; Brega, Nicoletta; Giaccone, Giuseppe

2011-01-01

Purpose To determine the maximum tolerated dose (MTD), toxicities, and pharmacokinetic-pharmacodynamic profile of the heat shock protein 90 (Hsp90) inhibitor PF-04929113 (SNX-5422) in patients with advanced solid tumors and lymphomas. Methods This was a single institution, phase I, dose-escalation study of PF-04929113 dosed twice-weekly. Endpoints included determination of dose-limiting toxicities (DLT), MTD, the safety profile of PF-04929113, pharmacodynamic assessment of PF-04929113 on Hsp70 induction, pharmacokinetic (PK) analysis of PF 04928473 (SNX-2112) and its prodrug PF-04929113 and assessment of response. Results Thirty three patients with advanced malignancies were treated. Dose escalation was continued up to 177 mg/m2 administered orally twice a week. One DLT (non-septic arthritis) was noted. No grade 4 adverse events (AEs) were seen; grade 3 AEs included diarrhea (9%), non-septic arthritis (3%), AST elevation (3%) and thrombocytopenia (3%). No objective responses were seen in 32 evaluable patients. Fifteen patients (47%) had stable disease; 17 patients (53%) had progressive disease. PK data revealed rapid absorption, hepatic and extra-hepatic clearance, extensive tissue binding and almost linear pharmacokinetics of the active drug PF 04928473. PD studies confirmed inhibition of Hsp90 and a linear correlation between PK parameters and Hsp70 induction. Conclusions PF-04929113 administered orally twice weekly is well tolerated and inhibits its intended target Hsp90. No objective responses were seen but long lasting stabilizations were obtained. Although no clinically significant drug-related ocular toxicity was seen in this study the development of PF-04929113 has been discontinued due to ocular toxicity seen in animal models and in a separate phase I study. PMID:21908572

Production and Study of High-Beta Plasma Confined by a Superconducting Dipole Magnet

NASA Astrophysics Data System (ADS)

Garnier, Darren

2005-10-01

The Levitated Dipole Experiment (LDX)http://psfcwww2.psfc.mit.edu/ldx/ is a new research facility that is exploring the confinement and stability of plasma created within the dipole field produced by a strong superconducting magnet. Unlike other configurations in which stability depends on curvature and magnetic shear, MHD stability of a dipole derives from plasma compressibility. Theoretically, the dipole magnetic geometry can stabilize a centrally-peaked plasma pressure that exceeds the local magnetic pressure (β> 1), and the absence of magnetic shear allows particle and energy confinement to decouple. In this presentation, the first experiments using the LDX facility are reported. Long-pulse, quasi-steady state microwave discharges lasting up to 12 seconds have been produced that are consistent with equilibria having peak beta values of 10%. Detailed measurements have been made of discharge evolution, plasma dynamics and instability, and the roles of gas fueling, microwave power deposition profiles, and plasma boundary shape. In these initial experiments, the high-field superconducting floating coil was supported by three thin supports and later the coil will be magnetically levitated. The plasma was created by multi- frequency electron cyclotron resonance heating at 2.45 and 6.4 GHz, and a population of energetic electrons, with mean energies above 50 keV, dominated the plasma pressure. Creation of high-pressure, high-beta plasma is only possible when intense hot electron interchange instabilities are stabilized sufficiently by a high background plasma density. A dramatic transition from a low-density, low-beta regime to a more quiescent, high-beta regime is observed when the plasma-fueling rate and confinement times are sufficiently long. External shaping coils are seen to modify the outer plasma boundary and affect the transition.

An industrial design solution for integrating NMR magnetic field sensors into an MRI scanner.

PubMed

Kennedy, Michael; Lee, Yoojin; Nagy, Zoltan

2018-08-01

Neuroimaging research relies on the skills of increasingly multidisciplinary individuals and often requires the installation and use of additional home-built or third-party equipment. The purpose of the present work was the safe, ergonomic, durable, and aesthetically pleasing installation of magnetic field monitoring equipment into a scanner, while keeping the setup compatible with standard operating procedures. An extensive set of steps was required to design a 3D printed solution to install a magnetic field camera into the eight-channel head coil of a 3T MRI scanner. First, the outer surface of the plastic coil housing was recreated into a 3D model, and the installation of the magnetic field sensors around this 3D model was performed in a virtual environment. The 3D printed solution was then assembled and tested for safety, reproducible performance, and image quality. The 3D printed solution holds the probes in stable positions and guides the necessary cables in an organized fashion and away from the volunteer. Assembly is easy and the solution is ergonomic, durable, and safe. We did not find excessive heating in the 3D printed parts, nor in the electronics, that they help to incorporate. The material used interferes minimally with transmit B1+ field. The design met all of the boundary conditions for a durable, safe, cost-effective, attractive, and functional installation. This work will provide the basis for installing the magnetic field sensors into other available head coils, and for designing the experimental setup for projects with varying experimental requirements. Magn Reson Med 80:833-839, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Centromedian-parafascicular deep brain stimulation induces differential functional inhibition of the motor, associative, and limbic circuits in large animals.

PubMed

Kim, Joo Pyung; Min, Hoon-Ki; Knight, Emily J; Duffy, Penelope S; Abulseoud, Osama A; Marsh, Michael P; Kelsey, Katherine; Blaha, Charles D; Bennet, Kevin E; Frye, Mark A; Lee, Kendall H

2013-12-15

Deep brain stimulation (DBS) of the centromedian-parafascicular (CM-Pf) thalamic nuclei has been considered an option for treating Tourette syndrome. Using a large animal DBS model, this study was designed to explore the network effects of CM-Pf DBS. The combination of DBS and functional magnetic resonance imaging is a powerful means of tracing brain circuitry and testing the modulatory effects of electrical stimulation on a neuronal network in vivo. With a within-subjects design, we tested the proportional effects of CM and Pf DBS by manipulating current spread and varying stimulation contacts in healthy pigs (n = 5). Our results suggests that CM-Pf DBS has an inhibitory modulating effect in areas that have been suggested as contributing to impaired sensory-motor and emotional processing. The results also help to define the differential neural circuitry effects of the CM and Pf with evidence of prominent sensorimotor/associative effects for CM DBS and prominent limbic/associative effects for Pf DBS. Our results support the notion that stimulation of deep brain structures, such as the CM-Pf, modulates multiple networks with cortical effects. The networks affected by CM-Pf stimulation in this study reinforce the conceptualization of Tourette syndrome as a condition with psychiatric and motor symptoms and of CM-Pf DBS as a potentially effective tool for treating both types of symptoms. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Inhibition of protein synthesis and malaria parasite development by drug targeting of methionyl-tRNA synthetases.

PubMed

Hussain, Tahir; Yogavel, Manickam; Sharma, Amit

2015-04-01

Aminoacyl-tRNA synthetases (aaRSs) are housekeeping enzymes that couple cognate tRNAs with amino acids to transmit genomic information for protein translation. The Plasmodium falciparum nuclear genome encodes two P. falciparum methionyl-tRNA synthetases (PfMRS), termed PfMRS(cyt) and PfMRS(api). Phylogenetic analyses revealed that the two proteins are of primitive origin and are related to heterokonts (PfMRS(cyt)) or proteobacteria/primitive bacteria (PfMRS(api)). We show that PfMRS(cyt) localizes in parasite cytoplasm, while PfMRS(api) localizes to apicoplasts in asexual stages of malaria parasites. Two known bacterial MRS inhibitors, REP3123 and REP8839, hampered Plasmodium growth very effectively in the early and late stages of parasite development. Small-molecule drug-like libraries were screened against modeled PfMRS structures, and several "hit" compounds showed significant effects on parasite growth. We then tested the effects of the hit compounds on protein translation by labeling nascent proteins with (35)S-labeled cysteine and methionine. Three of the tested compounds reduced protein synthesis and also blocked parasite growth progression from the ring stage to the trophozoite stage. Drug docking studies suggested distinct modes of binding for the three compounds, compared with the enzyme product methionyl adenylate. Therefore, this study provides new targets (PfMRSs) and hit compounds that can be explored for development as antimalarial drugs. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Tracking Glideosome-associated protein 50 reveals the development and organization of the inner membrane complex of Plasmodium falciparum.

PubMed

Yeoman, Jeffrey A; Hanssen, Eric; Maier, Alexander G; Klonis, Nectarios; Maco, Bohumil; Baum, Jake; Turnbull, Lynne; Whitchurch, Cynthia B; Dixon, Matthew W A; Tilley, Leann

2011-04-01

The most deadly of the human malaria parasites, Plasmodium falciparum, has different stages specialized for invasion of hepatocytes, erythrocytes, and the mosquito gut wall. In each case, host cell invasion is powered by an actin-myosin motor complex that is linked to an inner membrane complex (IMC) via a membrane anchor called the glideosome-associated protein 50 (PfGAP50). We generated P. falciparum transfectants expressing green fluorescent protein (GFP) chimeras of PfGAP50 (PfGAP50-GFP). Using immunoprecipitation and fluorescence photobleaching, we show that C-terminally tagged PfGAP50-GFP can form a complex with endogenous copies of the linker protein PfGAP45 and the myosin A tail domain-interacting protein (MTIP). Full-length PfGAP50-GFP is located in the endoplasmic reticulum in early-stage parasites and then redistributes to apical caps during the formation of daughter merozoites. In the final stage of schizogony, the PfGAP50-GFP profile extends further around the merozoite surface. Three-dimensional (3D) structured illumination microscopy reveals the early-stage IMC as a doubly punctured flat ellipsoid that separates to form claw-shaped apposed structures. A GFP fusion of PfGAP50 lacking the C-terminal membrane anchor is misdirected to the parasitophorous vacuole. Replacement of the acid phosphatase homology domain of PfGAP50 with GFP appears to allow correct trafficking of the chimera but confers a growth disadvantage.

Thermal stability of LiPF 6 salt and Li-ion battery electrolytes containing LiPF 6

NASA Astrophysics Data System (ADS)

Yang, Hui; Zhuang, Guorong V.; Ross, Philip N.

The thermal stability of the neat lithium hexafluorophosphate (LiPF 6) salt and of 1 molal (m) solutions of LiPF 6 in prototypical Li-ion battery solvents was studied with thermogravimetric analysis (TGA) and on-line Fourier transform infrared (FTIR). Pure LiPF 6 salt is thermally stable up to 107 °C in a dry inert atmosphere, and its decomposition path is a simple dissociation producing lithium fluoride (LiF) as solid and PF 5 as gaseous products. In the presence of water (300 ppm) in the carrier gas, its decomposition onset temperature is lowered as a result of direct thermal reaction between LiPF 6 and water vapor to form phosphorous oxyfluoride (POF 3) and hydrofluoric acid (HF). No new products were observed in 1 m solutions of LiPF 6 in ethylene carbonate (EC), dimethyl carbonate (DMC) and ethyl methyl carbonate (EMC) by on-line TGA-FTIR analysis. The storage of the same solutions in sealed containers at 85 °C for 300-420 h did not produce any significant quantity of new products as well. In particular, no alkylflurophosphates were found in the solutions after storage at elevated temperature. In the absence of either an impurity like alcohol or cathode active material that may (or may not) act as a catalyst, there is no evidence of thermally induced reaction between LiPF 6 and the prototypical Li-ion battery solvents EC, PC, DMC or EMC.

Cloning, sequence determination, and regulation of the ribonucleotide reductase subunits from Plasmodium falciparum: a target for antimalarial therapy.

PubMed Central

Rubin, H; Salem, J S; Li, L S; Yang, F D; Mama, S; Wang, Z M; Fisher, A; Hamann, C S; Cooperman, B S

1993-01-01

Malaria remains a leading cause of morbidity and mortality worldwide, accounting for more than one million deaths annually. We have focused on the reduction of ribonucleotides to 2'-deoxyribonucleotides, catalyzed by ribonucleotide reductase, which represents the rate-determining step in DNA replication as a target for antimalarial agents. We report the full-length DNA sequence corresponding to the large (PfR1) and small (PfR2) subunits of Plasmodium falciparum ribonucleotide reductase. The small subunit (PfR2) contains the major catalytic motif consisting of a tyrosyl radical and a dinuclear Fe site. Whereas PfR2 shares 59% amino acid identity with human R2, a striking sequence divergence between human R2 and PfR2 at the C terminus may provide a selective target for inhibition of the malarial enzyme. A synthetic oligopeptide corresponding to the C-terminal 7 residues of PfR2 inhibits mammalian ribonucleotide reductase at concentrations approximately 10-fold higher than that predicted to inhibit malarial R2. The gene encoding the large subunit (PfR1) contains a single intron. The cysteines thought to be involved in the reduction mechanism are conserved. In contrast to mammalian ribonucleotide reductase, the genes for PfR1 and PfR2 are located on the same chromosome and the accumulation of mRNAs for the two subunits follow different temporal patterns during the cell cycle. Images Fig. 2 Fig. 4 Fig. 5 PMID:8415692

Validation of the Spanish Version of the Food Allergy Quality of Life Questionnaire-Parent Form (S-FAQLQ-PF).

PubMed

Manso, L; Pineda, R; Huertas, B; Fernández-Rivas, M; Diéguez, M C; Cerecedo, I; Muriel, A; Fernández, F B; DunnGalvin, A; Antolín-Amérigo, D; De la Hoz, B

2017-01-01

Food allergy is an emerging health problem. Several questionnaires can be used to establish health-related quality of life (HRQOL) in food allergy patients. Current questionnaires should be translated in such a way that they take account of the culture of the country in which they are to be used. Objective: To translate and perform a cross-sectional validation of the Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF). The parents of 54 children diagnosed with food allergy were recruited to assess the Spanish version of the FAQLQ-PF (S-FQLQ-PF). The S-FQLQ-PF was translated into Spanish according to WHO guidelines (including a forward-backward translation). The statistical analysis showed that feasibility, reliability, and internal consistency were very good for the global S-FAQLQ-PF score and for the different domains. Assessment of construct validity indicated that S-FAQLQ-PF has reduced capacity for measurement of HRQOL in younger children. Cross-sectional validation of the S-FAQLQ-PF demonstrated that HRQOL of a Spanish pediatric population was affected by patient age, severity of symptoms, and number of reactions. HRQOL was not affected by sex, food implicated, number of foods implicated, ingestion of the implicated food, or presence of anaphylaxis. Translation into Spanish and cultural validation of the FAQLQ-PF demonstrated the influence of factors, such as patient age, severity of symptoms, and number of reactions on the HRQOL of a pediatric Spanish population.

Genetic diversity of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) and its effect on the performance of PfHRP2-based rapid diagnostic tests.

PubMed

Baker, Joanne; McCarthy, James; Gatton, Michelle; Kyle, Dennis E; Belizario, Vicente; Luchavez, Jennifer; Bell, David; Cheng, Qin

2005-09-01

Rising costs of antimalarial agents are increasing the demand for accurate diagnosis of malaria. Rapid diagnostic tests (RDTs) offer great potential to improve the diagnosis of malaria, particularly in remote areas. Many RDTs are based on the detection of Plasmodium falciparum histidine-rich protein (PfHRP) 2, but reports from field tests have questioned their sensitivity and reliability. We hypothesize that the variability in the results of PfHRP2-based RDTs is related to the variability in the target antigen. We tested this hypothesis by examining the genetic diversity of PfHRP2, which includes numerous amino acid repeats, in 75 P. falciparum lines and isolates originating from 19 countries and testing a subset of parasites by use of 2 PfHRP2-based RDTs. We observed extensive diversity in PfHRP2 sequences, both within and between countries. Logistic regression analysis indicated that 2 types of repeats were predictive of RDT detection sensitivity (87.5% accuracy), with predictions suggesting that only 84% of P. falciparum parasites in the Asia-Pacific region are likely to be detected at densities < or = 250 parasites/microL. Our data also indicated that PfHRP3 may play a role in the performance of PfHRP2-based RDTs. These findings provide an alternative explanation for the variable sensitivity in field tests of malaria RDTs that is not due to the quality of the RDTs.

Fabrication of the Superferric Cyclotron Gas-stopper Magnet at NSCL at Michigan State University

NASA Astrophysics Data System (ADS)

Chouhan, S. S.; Bollen, G.; DeKamp, J.; Green, M. A.; Lawton, D.; Magsig, C.; Morrissey, D. J.; Ottarson, J.; Schwarz, S.; Zeller, A. F.

2014-05-01

The magnet for the cyclotron gas stopper is a newly designed, large warm-iron superconducting cyclotron sector gradient dipole. The maximum field in the centre (gap = 0.18 m) is 2.7 T. The outer diameter of magnet yoke is 4.0 m, with a pole radius of 1.1 m and B*ρ = 1.8 T m. The fabrication and assembly of the iron return yoke and twelve pole pieces is complete. Separate coils are mounted on the return yokes that have a total mass of about 167 metric tons of iron. This paper illustrates the design and the fabrication process for the cyclotron gas-stopper magnet that is being fabricated at MSU.

Development of Compact Toroid Injector for C-2 FRCs

NASA Astrophysics Data System (ADS)

Matsumoto, Tadafumi; Sekiguchi, Junichi; Asai, Tomohiko; Gota, Hiroshi; Garate, Eusebio; Allfrey, Ian; Valentine, Travis; Smith, Brett; Morehouse, Mark; TAE Team

2014-10-01

Collaborative research project with Tri Alpha Energy has been started and we have developed a new compact toroid (CT) injector for the C-2 device, mainly for fueling field-reversed configurations (FRCs). The CT is formed by a magnetized coaxial plasma-gun (MCPG), which consists of coaxial cylinder electrodes; a spheromak-like plasma is generated by discharge and pushed out from the gun by Lorentz force. The inner diameter of outer electrode is 83.1 mm and the outer diameter of inner electrode is 54.0 mm. The surface of the inner electrode is coated with tungsten in order to reduce impurities coming out from the electrode. The bias coil is mounted inside of the inner electrode. We have recently conducted test experiments and achieved a supersonic CT translation speed of up to ~100 km/s. Other typical plasma parameters are as follows: electron density ~ 5 × 1021 m-3, electron temperature ~ 40 eV, and the number of particles ~0.5-1.0 × 1019. The CT injector is now planned to be installed on C-2 and the first CT injection experiment will be conducted in the near future. The detailed MCPG design as well as the test experimental results will be presented.

Absorber arc mitigation during CHI on NSTX

NASA Astrophysics Data System (ADS)

Mueller, D.; Bell, M. G.; Roquemore, A. L.; Raman, R.; Nelson, B. A.; Jarboe, T. R.

2009-11-01

A method of non-inductive startup, referred to as transient coaxial helicity injection (CHI), was successfully developed on the Helicity Injected Torus (HIT-II) experiment and employed on the National Spherical Torus Experiment (NSTX). This technique has produced 160 kA of plasma current on closed flux surfaces. Over 100 kA of the CHI current has been coupled to inductively driven current ramp-up. In transient CHI, a voltage is applied across the insulating gap separating the inner and outer vacuum vessel and gas is introduced at the lower gap (the injector). The resulting current in the injector follows the helical magnetic field connecting the electrodes, forms a toroidal current and expands into the vacuum vessel. At higher CHI current, the poloidal field due to the plasma can connect the inner and outer vessels at the insulating gap at the top (called the absorber) of NSTX and lower the impedance there. This results in arcs in the absorber which are a source of impurities and which reduce the desired current in the injector. Two coils installed in the absorber will be used to reduce the magnetic field across the absorber gap and mitigate the absorber arcs.

Rotatable electric cable connecting system

NASA Technical Reports Server (NTRS)

Manges, D. R. (Inventor)

1985-01-01

A cable reel assembly is described which is particularly adapted for, but not limited to, a system for providing electrical connection of power and data signals between an orbiter vehicle, such as a space shuttle, and a recovered satellite. The assembly is comprised of two mutually opposing ring type structures having 180 deg relative rotation with one of the structures being held in fixed position while the other structure is rotatable. Motor controlled berthing latches and umbilical cable connectors for the satellite are located on the rim of the rotatable ring structure. The electrical cable assembly is fed in two sections from the orbiter vehicle into the outer rim portion of the fixed ring structure where they are directed inwardly and attached to two concentrically coiled metal bands whose respective ends are secured to inner and outer post members of circular sets of guide pins located on opposing circular plate members, one rotatable and one fixed. The cable sections are fed out as three output cable sections through openings in the central portion of the circular plate of the rotatable ring structure where they are directed to the latches and connectors located on its rim.

Renal targeted delivery of triptolide by conjugation to the fragment peptide of human serum albumin.

PubMed

Yuan, Zhi-xiang; Wu, Xiao-juan; Mo, Jingxin; Wang, Yan-li; Xu, Chao-qun; Lim, Lee Yong

2015-08-01

We have previously demonstrated that peptide fragments (PFs) of the human serum albumin could be developed as potential renal targeting carriers, in particular, the peptide fragment, PF-A299-585 (A299-585 representing the amino acid sequence of the human serum albumin). In this paper, we conjugated triptolide (TP), the anti-inflammatory Chinese traditional medicine, to PF-A299-585 via a succinic acid spacer to give TPS-PF-A299-585 (TP loading 2.2% w/w). Compared with the free TP, TPS-PF-A299-585 exhibited comparable anti-inflammatory activity in the lipopolysaccharide stimulated MDCK cells, but was significantly less cytotoxic than the free drug. Accumulation of TPS-PF-A299-585 in the MDCK cells in vitro and in rodent kidneys in vivo was demonstrated using FITC-labeled TPS-PF-A299-585. Renal targeting was confirmed in vivo in a membranous nephropathic (MN) rodent model, where optical imaging and analyses of biochemical markers were combined to show that TPS-PF-A299-585 was capable of alleviating the characteristic symptoms of MN. The collective data affirm PF-A299-585 to be a useful carrier for targeting TP to the kidney. Copyright © 2015 Elsevier B.V. All rights reserved.

Platelet factor 4 (CXCL4) seals blood clots by altering the structure of fibrin.

PubMed

Amelot, Aymeric A; Tagzirt, Madjid; Ducouret, Guylaine; Kuen, René Lai; Le Bonniec, Bernard F

2007-01-05

Platelet factor-4 (PF4/CXCL4) is an orphan chemokine released in large quantities in the vicinity of growing blood clots. Coagulation of plasma supplemented with a matching amount of PF4 results in a translucent jelly-like clot. Saturating amounts of PF4 reduce the porosity of the fibrin network 4.4-fold and decrease the values of the elastic and loss moduli by 31- and 59-fold, respectively. PF4 alters neither the cleavage of fibrinogen by thrombin nor the cross-linking of protofibrils by activated factor XIII but binds to fibrin and dramatically transforms the structure of the ensuing network. Scanning electron microscopy showed that PF4 gives rise to a previously unreported pattern of polymerization where fibrin assembles to form a sealed network. The subunits constituting PF4 form a tetrahedron having at its corners a RPRH motif that mimics (in reverse orientation) the Gly-His-Arg-Pro-amide peptides that co-crystallize with fibrin. Molecular modeling showed that PF4 could be docked to fibrin with remarkable complementarities and absence of steric clashes, allowing the assembly of irregular polymers. Consistent with this hypothesis, as little as 50 microm the QVRPRHIT peptide derived from PF4 affects the polymerization of fibrin.

Focus is key: Panic-focused interpretations are associated with symptomatic improvement in panic-focused psychodynamic psychotherapy.

PubMed

Keefe, John R; Solomonov, Nili; Derubeis, Robert J; Phillips, Alexander C; Busch, Fredric N; Barber, Jacques P; Chambless, Dianne L; Milrod, Barbara L

2018-04-18

This study examines whether, in panic-focused psychodynamic psychotherapy (PFPP), interpretations of conflicts that underlie anxiety (panic-focused or PF-interpretations) are specifically associated with subsequent panic disorder (PD) symptom improvement, over and above the provision of non-symptom-focused interpretations. Technique use in Sessions 2 and 10 of a 24-session PFPP protocol was assessed for the 65 patients with complete outcome data randomized to PFPP in a two-site trial of psychotherapies for PD. Sessions were rated in 15-min segments for therapists' use of PF-interpretations, non-PF-interpretations, and PF-clarifications. Robust regressions were conducted to examine the relationship between these interventions and symptom change subsequent to the sampled session. Interpersonal problems were examined as a moderator of the relationship of PF-interpretations to symptom change. At Session 10, but not at Session 2, patients who received a higher degree of PF-interpretations experienced greater subsequent improvement in panic symptoms. Non-PF-interpretations were not predictive. Patients with more interpersonal distress benefitted particularly from the use of PF-interpretations at Session 10. By the middle phase of PFPP, panic-focused interpretations may drive subsequent improvements in panic symptoms, especially among patients with higher interpersonal distress. Interpretations of conflict absent a panic focus may not be especially helpful.

Electrically heated particulate filter enhanced ignition strategy

DOEpatents

Gonze, Eugene V; Paratore, Jr., Michael J

2012-10-23

An exhaust system that processes exhaust generated by an engine is provided. The system generally includes a particulate filter (PF) that filters particulates from the exhaust wherein an upstream end of the PF receives exhaust from the engine. A grid of electrically resistive material is applied to an exterior upstream surface of the PF and selectively heats exhaust passing through the grid to initiate combustion of particulates within the PF. A catalyst coating applied to at least one of the PF and the grid. A control module estimates a temperature of the grid and controls the engine to produce a desired exhaust product to increase the temperature of the grid.

Recognition and Binding of the PF2 Lectin to α-Amylase From Zabrotes subfasciatus (Coleoptera:Bruchidae) Larval Midgut

PubMed Central

Lagarda-Diaz, I.; Geiser, D.; Guzman-Partida, A.M.; Winzerling, J.; Vazquez-Moreno, L.

2014-01-01

Abstract Amylases are an important family of enzymes involved in insect carbohydrate metabolism that are required for the survival of insect larvae. For this reason, enzymes from starch-dependent insects are targets for insecticidal control. PF2 ( Olneya tesota ) is a lectin that is toxic to Zabrotes subfasciatus (Coleoptera: Bruchidae) larvae. In this study, we evaluated recognition of the PF2 lectin to α-amylases from Z. subfasciatus midgut and the effect of PF2 on α-amylase activity. PF2 caused a decrease of total amylase activity in vitro. Subsequently, several α-amylase isoforms were isolated from insect midgut tissues using ion exchange chromatography. Three enzyme isoforms were verified by an in-gel assay for amylase activity; however, only one isoform was recognized by antiamylase serum and PF2. The identity of this Z. subfasciatus α-amylase was confirmed by liquid chromatography−tandem mass spectrometry. The findings strongly suggest that a glycosylated α-amylase isoform from larval Z. subfasciatus midgut interacts with PF2, which interferes with starch digestion. PMID:25528751

A Structural Model for the Single-Stranded DNA Genome of Filamentous Bacteriophage Pf1†

PubMed Central

Tsuboi, Masamichi; Tsunoda, Masaru; Overman, Stacy A.; Benevides, James M.; Thomas, George J.

2010-01-01

The filamentous bacteriophage Pf1, which infects strain PAK of Pseudomonas aeruginosa, is a flexible filament (~2000 × 6.5 nm) consisting of a covalently closed DNA loop of 7349 nucleotides sheathed by 7350 copies of a 46-residue α-helical subunit. The subunit α-helices, which are inclined at a small average angle (~16°) from the virion axis, are arranged compactly around the DNA core. Orientations of the Pf1 DNA nucleotides with respect to the filament axis are not known. In this work we report and interpret the polarized Raman spectra of oriented Pf1 filaments. We demonstrate that the polarizations of DNA Raman band intensities establish that the nucleotide bases of packaged Pf1 DNA are well ordered within the virion and that the base planes are positioned close to parallel to the filament axis. The present results are combined with a previously proposed projection of the intraviral path of Pf1 DNA (1) to develop a novel molecular model for the Pf1 assembly. PMID:20078135

Structure-property relation and relevance of beam theories for microtubules: a coupled molecular and continuum mechanics study.

PubMed

Li, Si; Wang, Chengyuan; Nithiarasu, Perumal

2018-04-01

Quasi-one-dimensional microtubules (MTs) in cells enjoy high axial rigidity but large transverse flexibility due to the inter-protofilament (PF) sliding. This study aims to explore the structure-property relation for MTs and examine the relevance of the beam theories to their unique features. A molecular structural mechanics (MSM) model was used to identify the origin of the inter-PF sliding and its role in bending and vibration of MTs. The beam models were then fitted to the MSM to reveal how they cope with the distinct mechanical responses induced by the inter-PF sliding. Clear evidence showed that the inter-PF sliding is due to the soft inter-PF bonds and leads to the length-dependent bending stiffness. The Euler beam theory is found to adequately describe MT deformation when the inter-PF sliding is largely prohibited. Nevertheless, neither shear deformation nor the nonlocal effect considered in the 'more accurate' beam theories can fully capture the effect of the inter-PF sliding. This reflects the distinct deformation mechanisms between an MT and its equivalent continuous body.

SAM domain-dependent activity of PfTKL3, an essential tyrosine kinase-like kinase of the human malaria parasite Plasmodium falciparum.

PubMed

Abdi, Abdirahman; Eschenlauer, Sylvain; Reininger, Luc; Doerig, Christian

2010-10-01

Over the last decade, several protein kinases inhibitors have reached the market for cancer chemotherapy. The kinomes of pathogens represent potentially attractive targets in infectious diseases. The functions of the majority of protein kinases of Plasmodium falciparum, the parasitic protist responsible for the most virulent form of human malaria, remain unknown. Here we present a thorough characterisation of PfTKL3 (PF13_0258), an enzyme that belongs to the tyrosine kinase-like kinase (TKL) group. We demonstrate by reverse genetics that PfTKL3 is essential for asexual parasite proliferation in human erythrocytes. PfTKL3 is expressed in both asexual and gametocytes stages, and in the latter the protein co-localises with cytoskeleton microtubules. Recombinant PfTKL3 displays in vitro autophosphorylation activity and is able to phosphorylate exogenous substrates, and both activities are dramatically dependent on the presence of an N-terminal "sterile alpha-motif" domain. This study identifies PfTKL3 as a validated drug target amenable to high-throughput screening.

Improving sound absorption property of polyurethane foams doped with natural fiber

NASA Astrophysics Data System (ADS)

Azahari, M. Shafiq M.; Rus, Anika Zafiah M.; Taufiq Zaliran, M.; Kormin, Shaharuddin

2017-08-01

This study investigates the acoustics behavior of wood fibre filler of Red Meranti - filled polyurethane foam as a sound absorbing material. Three different thicknesses have been selected which is 10 mm, 20 mm and 30 mm. By choosing percentage loading of Red Meranti (RM) wood fibre of 5%, 10%, 15% and 20% added with polymer foam is namely as polymer foam (PF) composites of PF5%, PF10%, PF15% and PF20%. The sound absorption coefficient (α) and pore structure of the foam samples have been examined by using Impedance Tube test and Scanning Electron Microscopy (SEM). The results revealed that the highest thickness of highest filler loading (PF20%) gives higher sound absorption coefficient (α). The absorption frequency level is observed at 0.9922 and 0.99889 which contributed from low and high frequency absorption level respectively. The smallest pores size structure was observed with highest filler loading of PF. The higher the thickness and the higher the percentage loading of wood filler gives smaller pore structure, consequently, increased the sound absorption coefficient level.

Mutations in the P-Type Cation-Transporter ATPase 4, PfATP4, Mediate Resistance to Both Aminopyrazole and Spiroindolone Antimalarials

PubMed Central

2015-01-01

Aminopyrazoles are a new class of antimalarial compounds identified in a cellular antiparasitic screen with potent activity against Plasmodium falciparum asexual and sexual stage parasites. To investigate their unknown mechanism of action and thus identify their target, we cultured parasites in the presence of a representative member of the aminopyrazole series, GNF-Pf4492, to select for resistance. Whole genome sequencing of three resistant lines showed that each had acquired independent mutations in a P-type cation-transporter ATPase, PfATP4 (PF3D7_1211900), a protein implicated as the novel Plasmodium spp. target of another, structurally unrelated, class of antimalarials called the spiroindolones and characterized as an important sodium transporter of the cell. Similarly to the spiroindolones, GNF-Pf4492 blocks parasite transmission to mosquitoes and disrupts intracellular sodium homeostasis. Our data demonstrate that PfATP4 plays a critical role in cellular processes, can be inhibited by two distinct antimalarial pharmacophores, and supports the recent observations that PfATP4 is a critical antimalarial target. PMID:25322084

Sir2a regulates rDNA transcription and multiplication rate in the human malaria parasite Plasmodium falciparum

PubMed Central

Mancio-Silva, Liliana; Lopez-Rubio, Jose Juan; Claes, Aurélie; Scherf, Artur

2013-01-01

The Plasmodium falciparum histone deacetylase Sir2a localizes at telomeric regions where it contributes to epigenetic silencing of clonally variant virulence genes. Apart from telomeres, PfSir2a also accumulates in the nucleolus, which harbours the developmentally regulated ribosomal RNA genes. Here we investigate the nucleolar function of PfSir2a and demonstrate that PfSir2a fine-tunes ribosomal RNA gene transcription. Using a parasite line in which PfSir2a has been disrupted, we observe that histones near the transcription start sites of all ribosomal RNA genes are hyperacetylated and that transcription of ribosomal RNA genes is upregulated. Complementation of the PfSir2a-disrupted parasites restores the ribosomal RNA levels, whereas PfSir2a overexpression in wild-type parasites decreases ribosomal RNA synthesis. Furthermore, we observe that PfSir2a modulation of ribosomal RNA synthesis is linked to an altered number of daughter merozoites and the parasite multiplication rate. These findings provide new insights into an epigenetic mechanism that controls malaria parasite proliferation and virulence. PMID:23443558

Study of the interrelation between the electrotechnical parameters of the plasma focus discharge circuit and the plasma compression dynamics on the PF-3 and PF-1000 facilities

NASA Astrophysics Data System (ADS)

Mitrofanov, K. N.; Krauz, V. I.; Grabovski, E. V.; Myalton, V. V.; Vinogradov, V. P.; Paduch, M.; Scholz, M.; Karpiński, L.

2015-05-01

The main stages of the plasma current sheath (PCS) dynamics on two plasma focus (PF) facilities with different geometries of the electrode system, PF-3 (Filippov type) and PF-1000 (Mather type), were studied by analyzing the results of the current and voltage measurements. Some dynamic characteristics, such as the PCS velocity in the acceleration phase in the Mather-type facility (PF-1000), the moment at which the PCS reaches the anode end, and the plasma velocity in the radial stage of plasma compression in the PF-3 Filippov-type facility, were determined from the time dependence of the inductance of the discharge circuit with a dynamic plasma load. The energy characteristics of the discharge circuit of the compressing PCS were studied for different working gases (deuterium, argon, and neon) at initial pressures of 1.5-3 Torr in discharges with energies of 0.3-0.6 MJ. In experiments with deuterium, correlation between the neutron yield and the electromagnetic energy deposited directly in the compressed PCS was investigated.

Plantar fascia anatomy and its relationship with Achilles tendon and paratenon

PubMed Central

Stecco, Carla; Corradin, Marco; Macchi, Veronica; Morra, Aldo; Porzionato, Andrea; Biz, Carlo; De Caro, Raffaele

2013-01-01

Although the plantar fascia (PF) has been studied quite well from a biomechanical viewpoint, its microscopic properties have been overlooked: nothing is known about its content of elastic fibers, the features of the extracellular matrix or the extent of innervation. From a functional and clinical standpoint, the PF is often correlated with the triceps surae muscle, but the anatomical grounds for this link are not clear. The aim of this work was to focus on the PF macroscopic and microscopic properties and study how Achilles tendon diseases might affect it. Twelve feet from unembalmed human cadavers were dissected to isolate the PF. Specimens from each PF were tested with various histological and immunohistochemical stains. In a second stage, 52 magnetic resonance images (MRI) obtained from patients complaining of aspecific ankle or foot pain were analyzed, dividing the cases into two groups based on the presence or absence of signs of degeneration and/or inflammation of the Achilles tendon. The thickness of PF and paratenon was assessed in the two groups and statistical analyses were conducted. The PF is a tissue firmly joined to plantar muscles and skin. Analyzing its possible connections to the sural structures showed that this fascia is more closely connected to the paratenon of Achilles tendon than to the Achilles tendon, through the periosteum of the heel. The PF extended medially and laterally, continuing into the deep fasciae enveloping the abductor hallucis and abductor digiti minimi muscles, respectively. The PF was rich in hyaluronan, probably produced by fibroblastic-like cells described as ‘fasciacytes’. Nerve endings and Pacini and Ruffini corpuscles were present, particularly in the medial and lateral portions, and on the surface of the muscles, suggesting a role for the PF in the proprioception of foot. In the radiological study, 27 of the 52 MRI showed signs of Achilles tendon inflammation and/or degeneration, and the PF was 3.43 ± 0.48 mm thick (99%CI and SD = 0.95), as opposed to 2.09 ± 0.24 mm (99%CI, SD = 0.47) in the patients in which the MRI revealed no Achilles tendon diseases; this difference in thickness of 1.29 ± 0.57 mm (99%CI) was statistically significant (P < 0.001). In the group of 27/52 patients with tendinopathies, the PF was more than 4.5 mm thick in 5, i.e. they exceeded the threshold for a diagnosis of plantar fasciitis. None of the other 25/52 paitents had a PF more than 4 mm thick. There was a statistically significant correlation between the thicknesses of the PF and the paratenon. These findings suggest that the plantar fascia has a role not only in supporting the longitudinal arch of the foot, but also in its proprioception and peripheral motor coordination. Its relationship with the paratenon of the Achilles tendon is consistent with the idea of triceps surae structures being involved in the PF pathology, so their rehabilitation can be considered appropriate. Finally, the high concentration of hyaluronan in the PF points to the feasibility of using hyaluronan injections in the fascia to treat plantar fasciitis. PMID:24028383

Localization of quenches and mechanical disturbances in the Mu2e transport solenoid prototype using acoustic emission technique

DOE PAGES

Marchevsky, M.; Ambrosio, G.; Lamm, M.; ...

2016-02-12

Acoustic emission (AE) detection is a noninvasive technique allowing the localization of the mechanical events and quenches in superconducting magnets. Application of the AE technique is especially advantageous in situations where magnet integrity can be jeopardized by the use of voltage taps or inductive pickup coils. As the prototype module of the transport solenoid (TS) for the Mu2e experiment at Fermilab represents such a special case, we have developed a dedicated six-channel AE detection system and accompanying software aimed at localizing mechanical events during the coil cold testing. The AE sensors based on transversely polarized piezoceramic washers combined with cryogenicmore » preamplifiers were mounted at the outer surface of the solenoid aluminum shell, with a 60° angular step around the circumference. Acoustic signals were simultaneously acquired at a rate of 500 kS/s, prefiltered and sorted based on their arrival time. Next, based on the arrival timing, angular and axial coordinates of the AE sources within the magnet structure were calculated. Furthermore, we present AE measurement results obtained during cooldown, spot heater firing, and spontaneous quenching of the Mu2e TS module prototype and discuss their relevance for mechanical stability assessment and quench localization.« less

Application of a Saddle-Type Eddy Current Sensor in Steel Ball Surface-Defect Inspection

PubMed Central

Zhong, Mingming; Xie, Fengqin; Cao, Maoyong

2017-01-01

Steel ball surface-defect inspection was performed by using a new saddle-type eddy current sensor (SECS), which included a saddle coil and a signal conditioning circuit. The saddle coil was directly wound on the steel ball’s outer bracket in a semi-circumferential direction. Driven by a friction wheel, the test steel ball rotated in a one-dimensional direction, such that the steel ball surface was fully scanned by the SECS. There were two purposes for using the SECS in the steel ball inspection system: one was to reduce the complexity of the unfolding wheel of the surface deployment mechanism, and the other was to reduce the difficulty of sensor processing and installation. Experiments were carried out on bearing steel balls in diameter of 8 mm with three types of representative and typical defects by using the SECS, and the results showed that the inspection system can detect surface defects as small as 0.05 mm in width and 0.1 mm in depth with high-repetition detection accuracy, and the detection efficiency of 5 pcs/s, which meet the requirement for inspecting ISO grade 10 bearing steel balls. The feasibility of detecting steel ball surface defects by SECS was verified. PMID:29206154

A vector fetal magnetocardiogram system with high sensitivity

NASA Astrophysics Data System (ADS)

Kandori, Akihiko; Miyashita, Tsuyoshi; Tsukada, Keiji; Horigome, Hitoshi; Asaka, Mitsuhiro; Shigemitsu, Sadahiko; Takahashi, Miho; Terada, Yasushi; Mitsui, Toshio; Chiba, Yoshihide

1999-12-01

The vector fetal magnetocardiogram (V-FMCG) system that measures the three orthogonal components of the magnetic field from a fetal heart has been developed to clearly observe fetal cardiac activity during pregnancy by using the superconducting quantum interference device. To detect a clear V-FMCG signal, the bottom of the cryostat was made of thin glass-fiber-reinforced plastic and the total length between the pickup coil to the outer surface is 12 mm. Because the cryostat bottom was made thinner, the area of the cryostat's top and bottom could be made smaller, thus a low evaporation loss (<1.2 l per day) and a long refilling interval (>10 days) were obtained. The gantry was able to tilt the cryostat and the bed could move in three axis directions, which made it possible to easily locate the vector pickup coil at an optimum position to obtain the maximum magnetic field from a fetal heart. We obtained V-FMCGs from 21 normal fetuses with gestation periods of 27-38 weeks. Using these vector signals, the dipoles were estimated and the relationship between the strength of the dipole moments and the number of gestation weeks could be obtained. Thus, V-FMCG seems to represent a new noninvasive tool for clearly detecting the electrophysiological activity of a fetal heart.

Laser Direct Writing and Selective Metallization of Metallic Circuits for Integrated Wireless Devices.

PubMed

Cai, Jinguang; Lv, Chao; Watanabe, Akira

2018-01-10

Portable and wearable devices have attracted wide research attention due to their intimate relations with human daily life. As basic structures in the devices, the preparation of high-conductive metallic circuits or micro-circuits on flexible substrates should be facile, cost-effective, and easily integrated with other electronic units. In this work, high-conductive carbon/Ni composite structures were prepared by using a facile laser direct writing method, followed by an electroless Ni plating process, which exhibit a 3-order lower sheet resistance of less than 0.1 ohm/sq compared to original structures before plating, showing the potential for practical use. The carbon/Ni composite structures exhibited a certain flexibility and excellent anti-scratch property due to the tight deposition of Ni layers on carbon surfaces. On the basis of this approach, a wireless charging and storage device on a polyimide film was demonstrated by integrating an outer rectangle carbon/Ni composite coil for harvesting electromagnetic waves and an inner carbon micro-supercapacitor for energy storage, which can be fast charged wirelessly by a commercial wireless charger. Furthermore, a near-field communication (NFC) tag was prepared by combining a carbon/Ni composite coil for harvesting signals and a commercial IC chip for data storage, which can be used as an NFC tag for practical application.

A Structure Design Method for Reduction of MRI Acoustic Noise.

PubMed

Nan, Jiaofen; Zong, Nannan; Chen, Qiqiang; Zhang, Liangliang; Zheng, Qian; Xia, Yongquan

2017-01-01

The acoustic problem of the split gradient coil is one challenge in a Magnetic Resonance Imaging and Linear Accelerator (MRI-LINAC) system. In this paper, we aimed to develop a scheme to reduce the acoustic noise of the split gradient coil. First, a split gradient assembly with an asymmetric configuration was designed to avoid vibration in same resonant modes for the two assembly cylinders. Next, the outer ends of the split main magnet were constructed using horn structures, which can distribute the acoustic field away from patient region. Finally, a finite element method (FEM) was used to quantitatively evaluate the effectiveness of the above acoustic noise reduction scheme. Simulation results found that the noise could be maximally reduced by 6.9 dB and 5.6 dB inside and outside the central gap of the split MRI system, respectively, by increasing the length of one gradient assembly cylinder by 20 cm. The optimized horn length was observed to be 55 cm, which could reduce noise by up to 7.4 dB and 5.4 dB inside and outside the central gap, respectively. The proposed design could effectively reduce the acoustic noise without any influence on the application of other noise reduction methods.

Electrostatic-Dipole (ED) Fusion Confinement Studies

NASA Astrophysics Data System (ADS)

Miley, George H.; Shrestha, Prajakti J.; Yang, Yang; Thomas, Robert

2004-11-01

The Electrostatic-Dipole (ED) concept significantly differs from a "pure" dipole confinement device [1] in that the charged particles are preferentially confined to the high-pressure region interior of the dipole coil by the assistance of a surrounding spherical electrostatic grid. In present ED experiments, a current carrying coil is embedded inside the grid of an IEC such as to produce a magnetic dipole field. Charged particles are injected axisymmetrically from an ion gun (or duo-plasmatron) into the center of the ED confinement grid/dipole ring where they oscillate along the magnetic field lines and pass the peak field region at the center of the dipole region. As particles begin accelerating away from the center region towards the outer electrostatic grid region, they encounter a strong electrostatic potential (order of 10's of kilovolts) retarding force. The particles then decelerate, reverse direction and re-enter the dipole field region where again magnetic confinement dominates. This process continues, emulating a complex harmonic oscillator motion. The resulting pressure profile averaged over the field curvature offers good plasma stability in the ED configuration. The basic concept and results from preliminary experiments will be described. [1] M.E. Mauel, et al. "Dipole Equilibrium and Stability," 18th IAEA Conference of Plasma Phys. and Control. Nuclear Fusion, Varenna, Italy 2000, IAEA-F1-CN-70/TH

Linear magnetic spring and spring/motor combination

NASA Technical Reports Server (NTRS)

Patt, Paul J. (Inventor); Stolfi, Fred R. (Inventor)

1991-01-01

A magnetic spring, or a spring and motor combination, providing a linear spring force characteristic in each direction from a neutral position, in which the spring action may occur for any desired coordinate of a typical orthogonal coordinate system. A set of magnets are disposed, preferably symmetrically about a coordinate axis, poled orthogonally to the desired force direction. A second set of magnets, respectively poled opposite the first set, are arranged on the sprung article. The magnets of one of the sets are spaced a greater distance apart than those of the other, such that an end magnet from each set forms a pair having preferably planar faces parallel to the direction of spring force, the faces being offset so that in a neutral position the outer edge of the closer spaced magnet set is aligned with the inner edge of the greater spaced magnet set. For use as a motor, a coil can be arranged with conductors orthogonal to both the magnet pole directions and the direction of desired spring force, located across from the magnets of one set and fixed with respect to the magnets of the other set. In a cylindrical coordinate system having axial spring force, the magnets are radially poled and motor coils are concentric with the cylinder axis.

Conceptual design study for heat exhaust management in the ARC fusion pilot plant

NASA Astrophysics Data System (ADS)

Dennett, C. A.; Cao, N. M.; Creely, A. J.; Hecla, J.; Hoffman, H.; Kuang, A. Q.; Major, M.; Ruiz Ruiz, J.; Tinguely, R. A.; Tolman, E. A.; Brunner, D.; Labombard, B.; Sorbom, B. N.; Whyte, D. G.; Grover, P.; Laughman, C.

2017-10-01

The ARC pilot plant conceptual design study has been extended to explore solutions for managing heat exhaust resulting from 525 MW of fusion power in a compact (R 3.3 m) tokamak. Superconducting poloidal field coils are configured to produce double-null equilibria that support X-point target divertors while maintaining the original core plasma shape and toroidal field coil size. Long outer divertor legs are appended to the original vacuum vessel, providing both large surface areas for surface dissipation of radiative heat and significantly reduced neutron damage for divertor components. A molten salt FLiBe blanket adequately shields all superconductors and functions as a tritium breeder, with advanced neutronics calculations indicating a tritium breeding ratio of 1.08. In addition, FLiBe is used as the active coolant for the entire vessel. A tungsten swirl-tube cooling channel is implemented in the divertor, capable of exhausting 12 MW/m2, heat flux while keeping total FliBe pumping power below 1% of fusion power. Finally, three novel diagnostics are explored: Cherenkov radiation emitted in FLiBe to measure fusion reaction rate, microwave interferometry to measure divertor detachment front location, and IR imaging through the FLiBe blanket to monitor selected divertor ``hotspots.''

Diesel particulate filter regeneration via resistive surface heating

DOEpatents

Gonze, Eugene V; Ament, Frank

2013-10-08

An exhaust system that processes exhaust generated by an engine is provided. The system includes: a particulate filter (PF) that filters particulates from the exhaust wherein an upstream end of the PF receives exhaust from the engine; and a grid of electrically resistive material that is applied to an exterior upstream surface of the PF and that selectively heats exhaust passing through the grid to initiate combustion of particulates within the PF.

Enhanced Andreev reflection in gapped graphene

NASA Astrophysics Data System (ADS)

Majidi, Leyla; Zareyan, Malek

2012-08-01

We theoretically demonstrate unusual features of superconducting proximity effect in gapped graphene that presents a pseudospin symmetry-broken ferromagnet with a net pseudomagnetization. We find that the presence of a band gap makes the Andreev conductance of graphene superconductor/pseudoferromagnet (S/PF) junction to behave similar to that of a graphene ferromagnet-superconductor junction. The energy gap ΔN can enhance the pseudospin inverted Andreev conductance of S/PF junction to reach a limiting maximum value for ΔN≫μ, which depending on the bias voltage can be larger than the value for the corresponding junction with no energy gap. We further demonstrate a damped-oscillatory behavior for the local density of states of the PF region of S/PF junction and a long-range crossed Andreev reflection process in PF/S/PF structure with antiparallel alignment of pseudomagnetizations of PFs, which confirm that, in this respect, the gapped normal graphene behaves like a ferromagnetic graphene.

Role of Chromatin assembly factor 1 in DNA replication of Plasmodium falciparum.

PubMed

Gupta, Mohit Kumar; Agarawal, Meetu; Banu, Khadija; Reddy, K Sony; Gaur, Deepak; Dhar, Suman Kumar

2018-01-01

Nucleosome assembly in P. falciparum could be the key process in maintaining its genomic integrity as DNA replicates more than once per cell cycle during several stages of its life cycle. Here, we report the functional characterization of P. falciparum chromatin assembly factor 1 (CAF1), which interacts with several proteins namely PfCAF2, Histones, PfHP1 and others. Consistent with the above findings, we demonstrate the presence of PfCAF1 at the telomeric repeat regions, central and subtelomeric var genes of multiple var gene family along with PfHP1. Further, we report the upregulation of PfCAF1 after treatment with genotoxic agents like MMS and HU. Together, these findings establish role of PfCAF1 in heterochromatin maintenance and as histone chaperone in nucleosome assembly and DNA damage repair. Copyright © 2017 Elsevier Inc. All rights reserved.

Platelet factor-4 (CXCL4/PF-4): an angiostatic chemokine for cancer therapy.

PubMed

Wang, Zhe; Huang, He

2013-05-01

Platelet factor-4 (CXCL4/PF-4) is the first chemokine identified to have several biological functions. Notably, CXCL4/PF-4 inhibits endothelial cell proliferation and migration, leading to suppression of angiogenesis. Since angiogenesis is essential for the growth of most primary tumors and their subsequent metastases, it is a target for cancer therapy; due to its multiple functions, CXCL4/PF-4 is a potential clinical anti-tumor agent. This report reviews the mechanisms of CXCL4/PF-4 angiostatic activity, including interference with angiogenic growth factors bFGF-2 and VEGF165, activation of CXCR3B, interactions with integrins, interference with cell cycle, interactions with factors such as VEGF121 and CXCL8/IL-8, and derived molecules of CXCL4/PF-4 with angiostatic and anti-tumoral activities in different models in vivo or in vitro. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Body composition, muscle capacity, and physical function in older adults: an integrated conceptual model.

PubMed

Brady, Anne O; Straight, Chad R; Evans, Ellen M

2014-07-01

The aging process leads to adverse changes in body composition (increases in fat mass and decreases in skeletal muscle mass), declines in physical function (PF), and ultimately increased risk for disability and loss of independence. Specific components of body composition or muscle capacity (strength and power) may be useful in predicting PF; however, findings have been mixed regarding the most salient predictor of PF. The development of a conceptual model potentially aids in understanding the interrelated factors contributing to PF with the factors of interest being physical activity, body composition, and muscle capacity. This article also highlights sex differences in these domains. Finally, factors known to affect PF, such as sleep, depression, fatigue, and self-efficacy, are discussed. Development of a comprehensive conceptual model is needed to better characterize the most salient factors contributing to PF and to subsequently inform the development of interventions to reduce physical disability in older adults.

A 2-amino quinoline, 5-(3-(2-(7-chloroquinolin-2-yl)ethenyl)phenyl)-8-dimethylcarbamyl-4,6-dithiaoctanoic acid, interacts with PfMDR1 and inhibits its drug transport in Plasmodium falciparum.

PubMed

Edaye, Sonia; Reiling, Sarah J; Leimanis, Mara L; Wunderlich, Juliane; Rohrbach, Petra; Georges, Elias

2014-06-01

Malaria is a major disease in the tropics where chemotherapy remains the main mode of treatment and as such the rise and spread of drug-resistant malaria can lead to human tragedy. Two membrane transport proteins, PfMDR1 (Plasmodium falciparum multidrug resistance protein 1) and PfCRT (P. falciparum chloroquine resistance transporter), have been shown to cause resistance to several antimalarials. Both PfMDR1 and PfCRT are localized to the digestive vacuolar membrane and appear to regulate the transport of drugs and physiological metabolites. In this study we have used MK571, a 2-amino quinoline, to explore its interaction with PfMDR1 and PfCRT in chloroquine-sensitive and -resistant strains of P. falciparum. Our results show that chloroquine-resistant strains (e.g., K1, Dd2, and 7G8) are consistently more sensitive to MK571 than chloroquine-sensitive strains (e.g., 3D7, 106/1 and D10). This association, however, was not maintained with the chloroquine-resistant strain FCB which IC50 value was similar to chloroquine-sensitive strains. Moreover, the susceptibility of chloroquine-sensitive and -resistant strains to MK571 does not correlate with mutated PfCRT, nor is it reversible with verapamil; but correlates with mutations in PfMDR1. Furthermore, MK571 appears to target the parasite's digestive vacuole (DV), as demonstrated by the ability of MK571 to: (1) block the accumulation of the fluorescent dye Fluo-4 AM, a PfMDR1 substrate, into the digestive vacuole; (2) reduce the transvacuolar pH gradient; and (3) inhibit the formation of β-hematin in vitro. Moreover, the presence of non-toxic concentrations of MK571 sensitized both chloroquine-sensitive and -resistant parasites to mefloquine and halofantrine, likely by competing against PfMDR1-mediated sequestering of the drugs into the DV compartment and away from the drugs' cytosolic targets. Our data, nevertheless, found only a minimal decrease in MK571 IC50 value in FCB parasite which second pfmdr1 copy was inactivated via gene disruption. Taken together, the findings of this study suggest that MK571 interacts with native and mutant PfMDR1 and modulates the import of drugs or solutes into the parasite's DV and, as such, MK571 may be a useful tool in the characterization of PfMDR1 drug interactions and substrate specificity. Copyright © 2014 Elsevier B.V. All rights reserved.

Controlled human malaria infection by intramuscular and direct venous inoculation of cryopreserved Plasmodium falciparum sporozoites in malaria-naïve volunteers: effect of injection volume and dose on infectivity rates.

PubMed

Gómez-Pérez, Gloria P; Legarda, Almudena; Muñoz, Jose; Sim, B Kim Lee; Ballester, María Rosa; Dobaño, Carlota; Moncunill, Gemma; Campo, Joseph J; Cisteró, Pau; Jimenez, Alfons; Barrios, Diana; Mordmüller, Benjamin; Pardos, Josefina; Navarro, Mireia; Zita, Cecilia Justino; Nhamuave, Carlos Arlindo; García-Basteiro, Alberto L; Sanz, Ariadna; Aldea, Marta; Manoj, Anita; Gunasekera, Anusha; Billingsley, Peter F; Aponte, John J; James, Eric R; Guinovart, Caterina; Antonijoan, Rosa M; Kremsner, Peter G; Hoffman, Stephen L; Alonso, Pedro L

2015-08-07

Controlled human malaria infection (CHMI) by mosquito bite is a powerful tool for evaluation of vaccines and drugs against Plasmodium falciparum malaria. However, only a small number of research centres have the facilities required to perform such studies. CHMI by needle and syringe could help to accelerate the development of anti-malaria interventions by enabling centres worldwide to employ CHMI. An open-label CHMI study was performed with aseptic, purified, cryopreserved P. falciparum sporozoites (PfSPZ Challenge) in 36 malaria naïve volunteers. In part A, the effect of the inoculation volume was assessed: 18 participants were injected intramuscularly (IM) with a dose of 2,500 PfSPZ divided into two injections of 10 µL (n = 6), 50 µL (n = 6) or 250 µL (n = 6), respectively. In part B, the injection volume that resulted in highest infectivity rates in part A (10 µL) was used to formulate IM doses of 25,000 PfSPZ (n = 6) and 75,000 PfSPZ (n = 6) divided into two 10-µL injections. Results from a parallel trial led to the decision to add a positive control group (n = 6), each volunteer receiving 3,200 PfSPZ in a single 500-µL injection by direct venous inoculation (DVI). Four/six participants in the 10-µL group, 1/6 in the 50-µL group and 2/6 in the 250-µL group developed parasitaemia. Geometric mean (GM) pre-patent periods were 13.9, 14.0 and 15.0 days, respectively. Six/six (100%) participants developed parasitaemia in the 25,000 and 75,000 PfSPZ IM and 3,200 PfSPZ DVI groups. GM pre-patent periods were 12.2, 11.4 and 11.4 days, respectively. Injection of PfSPZ Challenge was well tolerated and safe in all groups. IM injection of 75,000 PfSPZ and DVI injection of 3,200 PfSPZ resulted in infection rates and pre-patent periods comparable to the bite of five PfSPZ-infected mosquitoes. Remarkably, it required 23.4-fold more PfSPZ administered IM than DVI to achieve the same parasite kinetics. These results allow for translation of CHMI from research to routine use, and inoculation of PfSPZ by IM and DVI regimens. ClinicalTrials.gov NCT01771848.

Monitoring Single-channel Water Permeability in Polarized Cells*

PubMed Central

Erokhova, Liudmila; Horner, Andreas; Kügler, Philipp; Pohl, Peter

2011-01-01

So far the determination of unitary permeability (pf) of water channels that are expressed in polarized cells is subject to large errors because the opening of a single water channel does not noticeably increase the water permeability of a membrane patch above the background. That is, in contrast to the patch clamp technique, where the single ion channel conductance may be derived from a single experiment, two experiments separated in time and/or space are required to obtain the single-channel water permeability pf as a function of the incremental water permeability (Pf,c) and the number (n) of water channels that contributed to Pf,c. Although the unitary conductance of ion channels is measured in the native environment of the channel, pf is so far derived from reconstituted channels or channels expressed in oocytes. To determine the pf of channels from live epithelial monolayers, we exploit the fact that osmotic volume flow alters the concentration of aqueous reporter dyes adjacent to the epithelia. We measure these changes by fluorescence correlation spectroscopy, which allows the calculation of both Pf,c and osmolyte dilution within the unstirred layer. Shifting the focus of the laser from the aqueous solution to the apical and basolateral membranes allowed the FCS-based determination of n. Here we validate the new technique by determining the pf of aquaporin 5 in Madin-Darby canine kidney cell monolayers. Because inhibition and subsequent activity rescue are monitored on the same sample, drug effects on exocytosis or endocytosis can be dissected from those on pf. PMID:21940624

Physical function mitigates the adverse effects of being thin on mortality in a free-living older Taiwanese cohort.

PubMed

Lee, M-S; Chen, R C-Y; Chang, Y-H; Huang, Y-C; Wahlqvist, M L

2012-01-01

To examine the significance of underweight and physical function as well as their interaction on mortality in the aged. Prospective cohort. The Elderly Nutrition and Health Survey in Taiwan during 1999-2000. Total of 1435 representative free-living elders (739 men and 696 women). Body composition was assessed by various anthropometrics. Physical function score (PF, ranged 0-100) was derived from the SF-36(®). Death by December 31, 2006 was the outcome measure. After 7.9 (median: 7.0) years follow-up, 381 (223 men, 158 women) of 1435 eligible participants had died. Those with the lowest PF (<45) had 3.43 (hazards ratio (HR), 95% confidence interval (CI) = 2.20-5.36) times the all-cause mortality risk of the highest PF (≥58). Interactions for PF and BMI (P =0.02) and for PF and wrist circumference (P =0.09) on death were found after controlling for potential confounders. Jointly, compared to normal-BMI-highest-PF, the greatest HR for death occurred where BMI <18.5 kg/m2 was combined with the lowest-PF after covariate adjustments (HR = 8.67, 95% CI = 3.77-20.0). Similarly, the lowest arm muscle circumference (MAMC)-PF had a HR of 5.22 compared to mid-MAMC-highest-PF. However, percent and absolute body fat, estimated by bioelectrical impedance, was comparable to non-sarcopenic individuals. Thin elderly Taiwanese with sarcopenia, and less skeleton, are at the most risk of death, especially if physical function is limited.

The secreted esterase of Propionibacterium freudenreichii has a major role in cheese lipolysis.

PubMed

Abeijón Mukdsi, María Claudia; Falentin, Hélène; Maillard, Marie-Bernadette; Chuat, Victoria; Medina, Roxana Beatriz; Parayre, Sandrine; Thierry, Anne

2014-01-01

Free fatty acids are important flavor compounds in cheese. Propionibacterium freudenreichii is the main agent of their release through lipolysis in Swiss cheese. Our aim was to identify the esterase(s) involved in lipolysis by P. freudenreichii. We targeted two previously identified esterases: one secreted esterase, PF#279, and one putative cell wall-anchored esterase, PF#774. To evaluate their role in lipolysis, we constructed overexpression and knockout mutants of P. freudenreichii CIRM-BIA1(T) for each corresponding gene. The sequences of both genes were also compared in 21 wild-type strains. All strains were assessed for their lipolytic activity on milk fat. The lipolytic activity observed matched data previously reported in cheese, thus validating the relevance of the method used. The mutants overexpressing PF#279 or PF#774 released four times more fatty acids than the wild-type strain, demonstrating that both enzymes are lipolytic esterases. However, inactivation of the pf279 gene induced a 75% reduction in the lipolytic activity compared to that of the wild-type strain, whereas inactivation of the pf774 gene did not modify the phenotype. Two of the 21 wild-type strains tested did not display any detectable lipolytic activity. Interestingly, these two strains exhibited the same single-nucleotide deletion at the beginning of the pf279 gene sequence, leading to a premature stop codon, whereas they harbored a pf774 gene highly similar to that of the other strains. Taken together, these results clearly demonstrate that PF#279 is the main lipolytic esterase in P. freudenreichii and a key agent of Swiss cheese lipolysis.

The Secreted Esterase of Propionibacterium freudenreichii Has a Major Role in Cheese Lipolysis

PubMed Central

Abeijón Mukdsi, María Claudia; Falentin, Hélène; Maillard, Marie-Bernadette; Chuat, Victoria; Medina, Roxana Beatriz; Parayre, Sandrine

2014-01-01

Free fatty acids are important flavor compounds in cheese. Propionibacterium freudenreichii is the main agent of their release through lipolysis in Swiss cheese. Our aim was to identify the esterase(s) involved in lipolysis by P. freudenreichii. We targeted two previously identified esterases: one secreted esterase, PF#279, and one putative cell wall-anchored esterase, PF#774. To evaluate their role in lipolysis, we constructed overexpression and knockout mutants of P. freudenreichii CIRM-BIA1T for each corresponding gene. The sequences of both genes were also compared in 21 wild-type strains. All strains were assessed for their lipolytic activity on milk fat. The lipolytic activity observed matched data previously reported in cheese, thus validating the relevance of the method used. The mutants overexpressing PF#279 or PF#774 released four times more fatty acids than the wild-type strain, demonstrating that both enzymes are lipolytic esterases. However, inactivation of the pf279 gene induced a 75% reduction in the lipolytic activity compared to that of the wild-type strain, whereas inactivation of the pf774 gene did not modify the phenotype. Two of the 21 wild-type strains tested did not display any detectable lipolytic activity. Interestingly, these two strains exhibited the same single-nucleotide deletion at the beginning of the pf279 gene sequence, leading to a premature stop codon, whereas they harbored a pf774 gene highly similar to that of the other strains. Taken together, these results clearly demonstrate that PF#279 is the main lipolytic esterase in P. freudenreichii and a key agent of Swiss cheese lipolysis. PMID:24242250

Solid state vibrational spectroscopy of anhydrous lithium hexafluorophosphate (LiPF6)

NASA Astrophysics Data System (ADS)

Kock, L. D.; Lekgoathi, M. D. S.; Crouse, P. L.; Vilakazi, B. M.

2012-10-01

Raman and infrared studies of solid anhydrous lithium hexafluorophosphate (LiPF6) have been carried out. The studies were complemented by X-ray powder diffraction (XRD) and Thermogravimetric (TG) analysis techniques. The results indicate that when solid LiPF6 is studied in a strictly anhydrous environment, more consistent thermal stability data can be obtained. TG analysis, using a scan rate of 10 °C min-1, indicate the onset of thermal decomposition of the anhydrous LiPF6 occurring at about 134.84 °C while the partially hydrolysed compound starts at 114.46 °C. The Raman spectra of anhydrous MPF6 (M = Li+, Na+ and K+) are best interpreted in terms of a cubic space group Fm3m(Ohs), (ZB = 1), giving rise to 21 vibrational modes (A1g(R)+Eg(R)+T1g+T2g(R)+3T1u(1R)+T2u) and as such, LiPF6 may be considered isostructural with NaPF6 and KPF6. Crystal symmetry distortions in the anhydrous LiPF6 give rise additional bands in the Raman spectrum due to T1u infrared active modes and the ν1 (A1g) Raman band appears in the infrared spectrum in violation of the mutual exclusion selection rule for centro-symmetric sites. When these observations are considered, the Raman spectrum of LiPF6 is similar to those of NaPF6 and KPF6, with observations of the expected shifts due to cation size and/or electronegativity effects.

Dienogest improves human leucocyte antigen-DR underexpression and reduces tumour necrosis factor-α production in peritoneal fluid cells from women with endometriosis.

PubMed

Maeda, N; Izumiya, C; Taniguchi, K; Matsushima, S; Mita, S; Shimizu, Y; Fukaya, T

2014-06-01

To determine the immunological effect of dienogest (DNG), an oral anti-endometriosis drug, on peritoneal fluid (PF) macrophages collected from women with endometriosis. Although it has been suggested that DNG has direct effects on endometriotic cells, including decreased cell proliferation and decreased anti-inflammatory cytokine production, the effects of DNG on PF cells are unclear. The effects of DNG on PF cells from 34 women with endometriosis and 22 women without endometriosis (controls) were investigated. Expression of human leucocyte antigen (HLA)-DR in PF macrophages, obtained from the peritoneal cavity during laparoscopic surgery, was determined by flow cytometry. HLA-DR expression was measured again after PF cells had been cultured for 72 h in a humidified atmosphere at 37 °C in 5% CO₂-95% air with or without DNG. After 72 h of incubation, the concentration of pro-inflammatory tumour necrosis factor (TNF)-α in the media was measured by enzyme-linked immunosorbent assay. HLA-DR expression was lower in PF macrophages from women with endometriosis compared with controls. However, after DNG treatment, HLA-DR expression in PF macrophages from women with endometriosis was increased to the same level as in controls. The TNF-α concentration in the media was decreased by DNG. DNG can restore the antigen-presenting ability of PF macrophages by increased HLA-DR expression, and may have an anti-inflammatory effect on PF macrophages in women with endometriosis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Pain interference and physical function demonstrate poor longitudinal association in people living with pain: a PROMIS investigation.

PubMed

Karayannis, Nicholas V; Sturgeon, John A; Chih-Kao, Ming; Cooley, Corinne; Mackey, Sean C

2017-06-01

A primary goal in managing pain is to reduce pain and increase physical function (PF). This goal is also tied to continuing payment for treatment services in many practice guidelines. Pain interference (PI) is often used as a proxy for measurement and reporting of PF in these guidelines. A common assumption is that reductions in PI will translate into improvement in PF over time. This assumption needs to be tested in a clinical environment. Consequently, we used the patient-reported outcomes measurement information system (PROMIS) to describe the topology of the longitudinal relationship between PI in relation to PF. Longitudinal data of 389 people with chronic pain seeking health care demonstrated that PI partially explained the variance in PF at baseline (r = -0.50) and over 90 days of care (r = -0.65). The relationship between pain intensity and PF was not significant when PI was included as a mediator. A parallel process latent growth curve model analysis showed a weak, unidirectional relationship (β = 0.18) between average PF scores and changes in PI over the course of 90 days of care, and no relationship between average PI scores and changes in PF across time. Although PI and PF seem moderately related when measured concurrently, they do not cluster closely together across time. The differential pathways between these 2 domains suggest that therapies that target both the consequences of pain on relevant aspects of persons' lives, and capability to perform physical activities are likely required for restoration of a vital life.

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

Peter H. Titus and Ali Zolfaghari

A critical design feature of any tokamak is the space taken up by the inner leg of the toroidal field (TF) coil. The radial build needed for the TF inner leg, along with shield thickness , size of the central solenoid and plasma minor radius set the major radius of the machine. The cost of the tokamak core roughly scales with the cube of the major radius. Small reductions in the TF build can have a big impact on the overall cost of the reactor. The cross section of the TF inner leg must structurally support the centering force andmore » that portion of the vertical separating force that is not supported by the outer structures. In this paper, the TF inner leg equatorial plane cross sections are considered. Out-of- Plane (OOP) forces must also be supported, but these are largest away from the equatorial plane, in the inner upper and lower corners and outboard sections of the TF coil. OOP forces are taken by structures that are not closely coupled with the radial build of the central column at the equatorial plane. The "Vertical Access AT Pilot Plant" currently under consideration at PPPL is used as a starting point for the structural, field and current requirements. Other TF structural concepts are considered. Most are drawn from existing designs such as ITER's circular conduits in radial plates bearing on a heavy nose section, and TPX's square conduits in a case, Each of these concepts can rely on full wedging, or partial wedging. Vaulted TF coils are considered as are those with some component of bucking against a central solenoid or bucking post. With the expectation that the pilot plant will be a steady state machine, a static stress criteria is used for all the concepts. The coils are assumed to be superconducting, with the superconductor not contributing to the structural strength. Limit analysis is employed to assess the degree of conservatism in the static criteria as it is applied to a linear elastic stress analysis. TF concepts, and in particular the PPPL AT PILOT plate concept are evaluated based on amount of space needed for structure and the amount of space left for superconductor.« less

Forward and Backward Aortic Components and Reflection Indexes in Children and Adolescents: Determinants and Role in High Pressure States.

PubMed

Zocalo, Yanina; Castro, Juan M; Garcia-Espinosa, Victoria; Curcio, Santiago; Chiesa, Pedro; Giachetto, Gustavo; Cabrera-Fischer, Edmundo I; Bia, Daniel

2018-04-12

High blood pressure states (HBP) would differ in wave components and reflections indexes, which could associate clinical and prognostic implications. 1) to characterize the association of aortic wave components and reflection parameters (backward [Pb], forward [Pf], Pb/Pf ratio and augmentation index [AIx]) with demographic, anthropometric, hemodynamic and arterial parameters in healthy children and adolescents; 2) to generate multivariate prediction models for the associations, to contribute to understand main determinants of Pf, Pb, Pb/Pf and AIx; 3) to identify if differences in wave reflection indexes observed in HBP could be explained by differences in the analyzed parameters. Healthy children and adolescents (n=816, females: 386; Age: 3-20 years) were studied. central aortic pressure and wave components (Pb, Pf, Pb/Pf and AIx determination with SphygmoCor [SCOR] and Mobil-o-Graph [MOG]); anthropometric assessment; regional arterial stiffness (carotid-femoral, carotid-radial pulse wave velocity [PWV] and PWV ratio); carotid intima-media thickness; carotid and femoral distensbility; cardiac output; systemic vascular resistances (SVR). Simple and multiple regression models were constructed to determine aortic wave parameters main explanatory variables. Normotensive and HBP groups were compared. Differences in wave reflection indexes were analyzed before and after controlling for explanatory variables. Equivalences between SphygmoCor and Mobil-O-Graph data were assessed (correlation and Bland-Altman analyses). There were systematic and proportional differences between data obtained with SphygmoCor and Mobil-O-Graph devices. Heart rate (HR), peripheral pulse pressure, height and weight were the variables that isolated (simple associations) or combined (multiple associations) showed the major capability to explain interindividual differences in Pf, Pb, Pb/Pf and AIx. Arterial stiffness also showed explanatory capacity, being the carotid the artery with major contribution. HBP associated higher Pf, Pb, AIx and lower Pb/Pf ratio. Those findings were observed together with higher weight, arterial stiffness and HR. After adjusting for anthropometric characteristics, HR, cardiac output and SVR, the HBP group showed greater Pf and Pb. Then, Pf and Pb characteristics associated with HBP would not be explained by anthropometric or hemodynamic factors. To evaluate wave components and reflection parameters could contribute to improve comprehension and management of HBP states. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Direct detection of falciparum and non-falciparum malaria DNA from a drop of blood with high sensitivity by the dried-LAMP system.

PubMed

Hayashida, Kyoko; Kajino, Kiichi; Simukoko, Humphrey; Simuunza, Martin; Ndebe, Joseph; Chota, Amos; Namangala, Boniface; Sugimoto, Chihiro

2017-01-13

Because of the low sensitivity of conventional rapid diagnostic tests (RDTs) for malaria infections, the actual prevalence of the diseases, especially those caused by non-Plasmodium falciparum (non-Pf) species, in asymptomatic populations remain less defined in countries lacking in well-equipped facilities for accurate diagnoses. Our direct blood dry LAMP system (CZC-LAMP) was applied to the diagnosis of malaria as simple, rapid and highly sensitive method as an alternative for conventional RDTs in malaria endemic areas where laboratory resources are limited. LAMP primer sets for mitochondria DNAs of Plasmodium falciparum (Pf) and human-infective species other than Pf (non-Pf; P. vivax, P. ovale, P. malariae) were designed and tested by using human blood DNA samples from 74 residents from a malaria endemic area in eastern Zambia. These malaria dry-LAMPs were optimized for field or point-of-care operations, and evaluated in the field at a malaria endemic area in Zambia with 96 human blood samples. To determine the sensitivities and specificities, results obtained by the on-site LAMP diagnosis were compared with those by the nested PCR and nucleotide sequencing of its product. The dry LAMPs showed the sensitivities of 89.7% for Pf and 85.7% for non-Pf, and the specificities of 97.2% for Pf and 100% for non-Pf, with purified blood DNA samples. The direct blood LAMP diagnostic methods, in which 1 μl of anticoagulated blood were used as the template, showed the sensitivities of 98.1% for Pf, 92.1% for non-Pf, and the specificities of 98.1% for Pf, 100% for non-Pf. The prevalences of P. falciparum, P. malariae and P. ovale in the surveyed area were 52.4, 25.3 and 10.6%, respectively, indicating high prevalence of asymptomatic carriers in endemic areas in Zambia. We have developed new field-applicable malaria diagnostic tests. The malaria CZC-LAMPs showed high sensitivity and specificity to both P. falciparum and non-P. falciparum. These malaria CZC-LAMPs provide new means for rapid, sensitive and reliable point-of-care diagnosis for low-density malaria infections, and are expected to help update current knowledge of malaria epidemiology, and can contribute to the elimination of malaria from endemic areas.

Plasmodium falciparum ookinete expression of plasmepsin VII and plasmepsin X.

PubMed

Li, Fengwu; Bounkeua, Viengngeun; Pettersen, Kenneth; Vinetz, Joseph M

2016-02-24

Plasmodium invasion of the mosquito midgut is a population bottleneck in the parasite lifecycle. Interference with molecular mechanisms by which the ookinete invades the mosquito midgut is one potential approach to developing malaria transmission-blocking strategies. Plasmodium aspartic proteases are one such class of potential targets: plasmepsin IV (known to be present in the asexual stage food vacuole) was previously shown to be involved in Plasmodium gallinaceum infection of the mosquito midgut, and plasmepsins VII and plasmepsin X (not known to be present in the asexual stage food vacuole) are upregulated in Plasmodium falciparum mosquito stages. These (and other) parasite-derived enzymes that play essential roles during ookinete midgut invasion are prime candidates for transmission-blocking vaccines. Reverse transcriptase PCR (RT-PCR) was used to determine timing of P. falciparum plasmepsin VII (PfPM VII) and plasmepsin X (PfPM X) mRNA transcripts in parasite mosquito midgut stages. Protein expression was confirmed by western immunoblot and immunofluorescence assays (IFA) using anti-peptide monoclonal antibodies (mAbs) against immunogenic regions of PfPM VII and PfPM X. These antibodies were also used in standard membrane feeding assays (SMFA) to determine whether inhibition of these proteases would affect parasite transmission to mosquitoes. The Mann-Whitney U test was used to analyse mosquito transmission assay results. RT-PCR, western immunoblot and immunofluorescence assay confirmed expression of PfPM VII and PfPM X in mosquito stages. Whereas PfPM VII was expressed in zygotes and ookinetes, PfPM X was expressed in gametes, zygotes, and ookinetes. Antibodies against PfPM VII and PfPM X decreased P. falciparum invasion of the mosquito midgut when used at high concentrations, indicating that these proteases play a role in Plasmodium mosquito midgut invasion. Failure to generate genetic knockouts of these genes limited determination of the precise role of these proteases in parasite transmission but suggests that they are essential during the intraerythrocytic life cycle. PfPM VII and PfPM X are present in the mosquito-infective stages of P. falciparum. Standard membrane feeding assays demonstrate that antibodies against these proteins reduce the infectivity of P. falciparum for mosquitoes, suggesting their viability as transmission-blocking vaccine candidates. Further study of the role of these plasmepsins in P. falciparum biology is warranted.

Fluorimetric study on the interaction between Norfloxacin and Proflavine hemisulphate.

PubMed

More, Vishalkumar R; Anbhule, Prashant V; Lee, Sang H; Patil, Shivajirao R; Kolekar, Govind B

2011-07-01

The interaction between Norfloxacin (NF) and Proflavine hemisulphate (PF) was investigated by spectroscopic tools like UV-VIS absorption and Fluorescence spectroscopy. It was proved that fluorescence quenching of NF by PF is due to the formation of NF-PF complex which was supported by UV-VIS absorption study. The study of thermodynamic parameters suggested that the key interacting forces are hydrogen bond and van der Waal's interactions and the binding interaction was spontaneous. The distance r between NF and PF was obtained according to the Förster's theory of non-radiative energy transfer. The fluorescence quenching mechanism was applied to estimate PF directly from pharmaceutical samples. © Springer Science+Business Media, LLC 2011

A Novel Acidic Matrix Protein, PfN44, Stabilizes Magnesium Calcite to Inhibit the Crystallization of Aragonite*

PubMed Central

Pan, Cong; Fang, Dong; Xu, Guangrui; Liang, Jian; Zhang, Guiyou; Wang, Hongzhong; Xie, Liping; Zhang, Rongqing

2014-01-01

Magnesium is widely used to control calcium carbonate deposition in the shell of pearl oysters. Matrix proteins in the shell are responsible for nucleation and growth of calcium carbonate crystals. However, there is no direct evidence supporting a connection between matrix proteins and magnesium. Here, we identified a novel acidic matrix protein named PfN44 that affected aragonite formation in the shell of the pearl oyster Pinctada fucata. Using immunogold labeling assays, we found PfN44 in both the nacreous and prismatic layers. In shell repair, PfN44 was repressed, whereas other matrix proteins were up-regulated. Disturbing the function of PfN44 by RNAi led to the deposition of porous nacreous tablets with overgrowth of crystals in the nacreous layer. By in vitro circular dichroism spectra and fluorescence quenching, we found that PfN44 bound to both calcium and magnesium with a stronger affinity for magnesium. During in vitro calcium carbonate crystallization and calcification of amorphous calcium carbonate, PfN44 regulated the magnesium content of crystalline carbonate polymorphs and stabilized magnesium calcite to inhibit aragonite deposition. Taken together, our results suggested that by stabilizing magnesium calcite to inhibit aragonite deposition, PfN44 participated in P. fucata shell formation. These observations extend our understanding of the connections between matrix proteins and magnesium. PMID:24302723

Identifying and describing feelings and psychological flexibility predict mental health in men with HIV.

PubMed

Landstra, Jodie M B; Ciarrochi, Joseph; Deane, Frank P; Hillman, Richard J

2013-11-01

Difficulty identifying and describing feelings (DIDF) and psychological flexibility (PF) predict poor emotional adjustment. To examine the relationship between DIDF and PF and whether DIDF and low PF would put men undergoing cancer screening at risk for poor adjustment. Longitudinal self-report survey. Two hundred and one HIV-infected men who have sex with men participated in anal cancer screening at two time points over 14 weeks. Psychological flexibility was assessed by the Acceptance and Action Questionnaire II and DIDF by the Toronto Alexithymia Scale-20. We also measured depression, anxiety, stress (DASS) and health-related quality of life (QOL; SF-12). Both DIDF and PF were reliable predictors of mental health. When levels of baseline mental health were controlled, greater DIDF predicted increases in Time 2 depression, anxiety and stress and decreases in mental and physical QOL. The link between PF and mental health was entirely mediated by DIDF. Being chronically low in PF could lead to greater DIDF and thereby worse mental health. Having more PF promotes the ability to identify and differentiate the nuances of pleasant and unpleasant emotions, which enhances an individual's mental health. Intentionally enhancing men's ability to identify and describe feelings or PF may assist them to better manage a range of difficult life experiences such as health screenings and other potentially threatening information. © 2013 The British Psychological Society.

Induction of anti-PF4/heparin antibodies after arthroplasty for rheumatic diseases.

PubMed

Migita, Kiyoshi; Asano, Tomoyuki; Sato, Shuzo; Motokawa, Satoru

2018-04-17

Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin therapy caused by antibodies to complexes of platelet factor 4 (PF4) and heparin. These pathogenic antibodies against PF4/heparin bind and activate cellular FcγRIIa on platelets to induce a hypercoagulable state culminating in thrombosis. Recent studies indicate several conditions, including joint surgery, induce spontaneous HIT, which can occur without exposure to heparin. To determine the real-world evidences concerning the incidences of venous thromboembolism (VTE) after total joint arthroplasty for rheumatic disease, we conducted a multicenter cohort study (J-PSVT) designed to document the VTE and seroconversion rates of anti-PF4/heparin antibody in 34 Japanese National hospital organization (NHO) hospitals. J-PSVT indicated that prophylaxis with fondaparinux, not enoxaparin, reduces the risk of deep vein thrombosis in patients undergoing arthroplasty. Multivariate analysis revealed that dynamic mechanical thromboprophylaxis (intermittent plantar device) was an independent risk factor for seroconversion of anti-PF4/heparin antibodies, which was also confirmed by propensity-score matching. Seroconversion rates of anti-PF4/heparin antibodies were significantly reduced in rheumatoid arthritis (RA) patients compared with osteoarthritis (OA) patients, which may link with the findings that IgG fractions isolated from RA patients not OA patients contained PF4. Our study indicated that a unique profile of anti-PF4/heparin antibodies is induced by arthroplasty for rheumatic diseases.

Pseudomonas protegens Pf-5 favours self-produced siderophore over free-loading in interspecies competition for iron.

PubMed

Sexton, D Joseph; Glover, Rochelle C; Loper, Joyce E; Schuster, Martin

2017-09-01

Many microorganisms compete for extracellular iron using strain-specific chelators known as siderophores. The ferric-siderophore complex limits local access to iron because import requires a suitable cognate receptor. Interestingly, many species carry receptors that enable 'cross-feeding' on heterologous siderophores made by neighboring organisms, although little is known about how this ubiquitous behaviour is regulated. Here, we investigated the soil bacterium Pseudomonas protegens Pf-5, a strain remarkable for its ability to use dozens of heterologous siderophores. We characterized the expression of six pyoverdine-type (PVD) siderophore receptors in response to their cognate PVD. In general, we found expression is tightly regulated to reflect availability of their cognate PVD. In contrast, Pf-5 continues to secrete its own primary siderophore, PVD Pf-5 , despite the capability and opportunity to cross-feed. We demonstrate that this strategy is beneficial in co-culture with a competing PVD PAO1 -producer, P. aeruginosa PAO1. Although Pf-5 can cross-feed on PVD PAO1 , production of PVD Pf-5 is required to maintain a competitive advantage. We attribute this to an antagonistic effect of PVD Pf-5 on the growth of PAO1, presumably through limiting access to iron. Our results demonstrate the benefits of excluding competitors out-weigh the incentives associated with a free-loader lifestyle for Pf-5. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

Trophic response of the intestinal mucosa to inflammation in rats injected with turpentine: a study using pair-fed controls.

PubMed

Zarrabian, S; Fromont, G; Tran, T; Macry, J; Biou, D; Mendy, F; Roger, L; Cezard, J P

1999-10-01

The effects of restricted food intake and acute inflammation on the small bowel were studied, Wistar rats (250 g) were given subcutaneous injections of turpentine (TR) and compared to two control groups, at 18, 42 and 66 h. One was fed ad libitum (C), the other was pair fed (PF) with TR. The TR and PF rats showed hypoplasia of the jejunal mucosa with decreased protein and DNA contents at 42 h and 66 h. The hypoplasia resulted in a reduced villus height that was significantly different from the controls at 66 h (C: 468 +/- 17, TR[66] : 376 +/- 20, PF[66] : 258 +/- 2.9 microm, P<0.001). This decrease in villus height was significantly greater in the PF rats than in the TR rats at 66 h. The crypt height/villus height (C/V) ratio in the PF rats was greater than in the TR group at all times. However, the protein and DNA contents in the TR group were significantly higher than in the PF group at 42 h and 66 h (TR/PF[42] : 29.5 +/- 1.9 vs 20.5 +/- 2.0, P< 0.001, [66]: 25.8 +/- 2.0 vs 16.6 +/- 1.3 mg/10 cm, P,< 0.001). Disaccharidase activities (sucrase and glucoamylase) per 10 cm jejunum at 66 h were significantly lower in the PF group than in the control and TR groups (sucrase mU/10cm[66] C : 3090 +/- 144, TR 2683 +/- 479, PF 1969 +/- 144, P,< 0.001; glucoamylase mU/10 cm[66] 237 +/- 25, TR 169 +/- 40, PF 123 +/- 5, P< 0.01). The N-aminopeptidase patterns in the TR and PF groups were similar. These data suggest that dietary restriction during acute inflammation is the main factor causing hypoplasia of the jejunal mucosa. However, acute inflammation has a trophic effect on the morphological and function of the mucosa. This effect is probably due to inflammatory mediators, whose synthesis is stimulated by turpentine.

The Plasmodium falciparum exported protein PF3D7_0402000 binds to erythrocyte ankyrin and band 4.1

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

Shakya, Bikash; Penn, Wesley D.; Nakayasu, Ernesto S.

Plasmodium falciparum extensively modifies the infected red blood cell (RBC), resulting in changes in deformability, shape and surface properties. These alterations suggest that the RBC cytoskeleton is a major target for modification during infection. However, the molecular mechanisms leading to these changes are largely unknown. To begin to address this question, we screened for exported P. falciparum proteins that bound to the erythrocyte cytoskeleton proteins ankyrin 1 (ANK1) and band 4.1 (4.1R), which form critical interactions with other cytoskeletal proteins that contribute to the deformability and stability of RBCs. Yeast two-hybrid screens with ANK1 and 4.1R identified eight interactions withmore » P. falciparum exported proteins, including an interaction between 4.1R and PF3D7_0402000 (PFD0090c). This interaction was first identified in a large-scale screen (Vignali et al., Malaria J, 7:211, 2008), which also reported an interaction between PF3D7_0402000 and ANK1. We confirmed the interactions of PF3D7_0402000 with 4.1R and ANK1 in pair-wise yeast two-hybrid and co-precipitation assays. In both cases, an intact PHIST domain in PF3D7_0402000 was required for binding. Complex purification followed by mass spectrometry analysis provided additional support for the interaction of PF3D7_0402000 with ANK1 and 4.1R. RBC ghost cells loaded with maltose-binding protein (MBP)-PF3D7_0402000 passed through a metal microsphere column less efficiently than mock- or MBP-loaded controls, consistent with an effect of PF3D7_0402000 on RBC rigidity or membrane stability. This study confirmed the interaction of PF3D7_0402000 with 4.1R in multiple independent assays, provided the first evidence that PF3D7_0402000 also binds to ANK1, and suggested that PF3D7_0402000 affects deformability or membrane stability of uninfected RBC ghosts.« less

Plantar fascia anatomy and its relationship with Achilles tendon and paratenon.

PubMed

Stecco, Carla; Corradin, Marco; Macchi, Veronica; Morra, Aldo; Porzionato, Andrea; Biz, Carlo; De Caro, Raffaele

2013-12-01

Although the plantar fascia (PF) has been studied quite well from a biomechanical viewpoint, its microscopic properties have been overlooked: nothing is known about its content of elastic fibers, the features of the extracellular matrix or the extent of innervation. From a functional and clinical standpoint, the PF is often correlated with the triceps surae muscle, but the anatomical grounds for this link are not clear. The aim of this work was to focus on the PF macroscopic and microscopic properties and study how Achilles tendon diseases might affect it. Twelve feet from unembalmed human cadavers were dissected to isolate the PF. Specimens from each PF were tested with various histological and immunohistochemical stains. In a second stage, 52 magnetic resonance images (MRI) obtained from patients complaining of aspecific ankle or foot pain were analyzed, dividing the cases into two groups based on the presence or absence of signs of degeneration and/or inflammation of the Achilles tendon. The thickness of PF and paratenon was assessed in the two groups and statistical analyses were conducted. The PF is a tissue firmly joined to plantar muscles and skin. Analyzing its possible connections to the sural structures showed that this fascia is more closely connected to the paratenon of Achilles tendon than to the Achilles tendon, through the periosteum of the heel. The PF extended medially and laterally, continuing into the deep fasciae enveloping the abductor hallucis and abductor digiti minimi muscles, respectively. The PF was rich in hyaluronan, probably produced by fibroblastic-like cells described as 'fasciacytes'. Nerve endings and Pacini and Ruffini corpuscles were present, particularly in the medial and lateral portions, and on the surface of the muscles, suggesting a role for the PF in the proprioception of foot. In the radiological study, 27 of the 52 MRI showed signs of Achilles tendon inflammation and/or degeneration, and the PF was 3.43 ± 0.48 mm thick (99%CI and SD = 0.95), as opposed to 2.09 ± 0.24 mm (99%CI, SD = 0.47) in the patients in which the MRI revealed no Achilles tendon diseases; this difference in thickness of 1.29 ± 0.57 mm (99%CI) was statistically significant (P < 0.001). In the group of 27/52 patients with tendinopathies, the PF was more than 4.5 mm thick in 5, i.e. they exceeded the threshold for a diagnosis of plantar fasciitis. None of the other 25/52 paitents had a PF more than 4 mm thick. There was a statistically significant correlation between the thicknesses of the PF and the paratenon. These findings suggest that the plantar fascia has a role not only in supporting the longitudinal arch of the foot, but also in its proprioception and peripheral motor coordination. Its relationship with the paratenon of the Achilles tendon is consistent with the idea of triceps surae structures being involved in the PF pathology, so their rehabilitation can be considered appropriate. Finally, the high concentration of hyaluronan in the PF points to the feasibility of using hyaluronan injections in the fascia to treat plantar fasciitis. © 2013 Anatomical Society.

Patients and families as teachers: a mixed methods assessment of a collaborative learning model for medical error disclosure and prevention.

PubMed

Langer, Thorsten; Martinez, William; Browning, David M; Varrin, Pamela; Sarnoff Lee, Barbara; Bell, Sigall K

2016-08-01

Despite growing interest in engaging patients and families (P/F) in patient safety education, little is known about how P/F can best contribute. We assessed the feasibility and acceptability of a patient-teacher medical error disclosure and prevention training model. We developed an educational intervention bringing together interprofessional clinicians with P/F from hospital advisory councils to discuss error disclosure and prevention. Patient focus groups and orientation sessions informed curriculum and assessment design. A pre-post survey with qualitative and quantitative questions was used to assess P/F and clinician experiences and attitudes about collaborative safety education including participant hopes, fears, perceived value of learning experience and challenges. Responses to open-ended questions were coded according to principles of content analysis. P/F and clinicians hoped to learn about each other's perspectives, communication skills and patient empowerment strategies. Before the intervention, both groups worried about power dynamics dampening effective interaction. Clinicians worried that P/F would learn about their fallibility, while P/F were concerned about clinicians' jargon and defensive posturing. Following workshops, clinicians valued patients' direct feedback, communication strategies for error disclosure and a 'real' learning experience. P/F appreciated clinicians' accountability, and insights into how medical errors affect clinicians. Half of participants found nothing challenging, the remainder clinicians cited emotions and enormity of 'culture change', while P/F commented on medical jargon and desire for more time. Patients and clinicians found the experience valuable. Recommendations about how to develop a patient-teacher programme in patient safety are provided. An educational paradigm that includes patients as teachers and collaborative learners with clinicians in patient safety is feasible, valued by clinicians and P/F and promising for P/F-centred medical error disclosure and prevention training. 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/

Effects of stand age and soil properties on soil bacterial and fungal community composition in Chinese pine plantations on the Loess Plateau

PubMed Central

Dang, Peng; Yu, Xuan; Le, Hien; Liu, Jinliang; Shen, Zhen

2017-01-01

The effects of Chinese pine (Pinus tabuliformis) on soil variables after afforestation have been established, but microbial community changes still need to be explored. Using high-throughput sequencing technology, we analyzed bacterial and fungal community composition and diversity in soils from three stands of different-aged, designated 12-year-old (PF1), 29-year-old (PF2), and 53-year-old (PF3), on a Chinese pine plantation and from a natural secondary forest (NSF) stand that was almost 80 years old. Abandoned farmland (BL) was also analyzed. Shannon index values of both bacterial and fungal community in PF1 were greater than those in PF2, PF3 and NSF. Proteobacteria had the lowest abundance in BL, and the abundance increased with stand age. The abundance of Actinobacteria was greater in BL and PF1 soils than those in other sites. Among fungal communities, the dominant taxa were Ascomycota in BL and PF1 and Basidiomycota in PF2, PF3 and NSF, which reflected the successional patterns of fungal communities during the development of Chinese pine plantations. Therefore, the diversity and dominant taxa of soil microbial community in stands 12 and 29 years of age appear to have undergone significant changes; afterward, the soil microbial community achieved a relatively stable state. Furthermore, the abundances of the most dominant bacterial and fungal communities correlated significantly with organic C, total N, C:N, available N, and available P, indicating the dependence of these microbes on soil nutrients. Overall, our findings suggest that the large changes in the soil microbial community structure of Chinese pine plantation forests may be attributed to the phyla present (e.g., Proteobacteria, Actinobacteria, Ascomycota and Basidiomycota) which were affected by soil carbon and nutrients in the Loess Plateau. PMID:29049349

[11C]PF-3274167 as a PET radiotracer of oxytocin receptors: Radiosynthesis and evaluation in rat brain.

PubMed

Vidal, Benjamin; Karpenko, Iuliia A; Liger, François; Fieux, Sylvain; Bouillot, Caroline; Billard, Thierry; Hibert, Marcel; Zimmer, Luc

2017-12-01

Oxytocin plays a major role in the regulation of social interactions in mammals by interacting with the oxytocin receptor (OTR) expressed in the brain. Furthermore, the oxytocin system appears as a possible therapeutic target in autism spectrum disorders and other psychiatric troubles, justifying current pharmacological researches. Since no specific PET radioligand is currently available to image OTR in the brain, the aim of this study was to radiolabel the specific OTR antagonist PF-3274167 and to evaluate [ 11 C]PF-3274167 as a potential PET tracer for OTR in rat brains. [ 11 C]PF-3274167 was prepared via the O-methylation of its desmethyl precursor with [ 11 C]methyl iodide. The lipophilicity of the radioactive compound was evaluated by measuring the n-octanol-buffer partition coefficient (logD). Autoradiography experiments were performed on rat brain tissue to evaluate the in vitro distribution of the [ 11 C]PF-3274167. MicroPET experiments were conducted with and without pre-injection of ciclosporin in order to evaluate the influence of the P-glycoprotein (P-gp) on the brain uptake. [ 11 C]PF-3274167 was synthesized with high radiochemical and chemical purities (>95%) and good specific activity. The measured logD was 1.93. In vitro, [ 11 C]PF-3274167 did not show any evidence of specific binding to OTR. PET imaging showed that [ 11 C]PF-3274167 uptake in rat brain was very low in basal conditions but increased significantly after the administration of ciclosporin, suggesting that it is a substrate of the P-gp. In the ciclosporin-pre-injected rat, however, [ 11 C]PF-3274167 distribution did not match with the known distribution of OTR in rats. [ 11 C]PF-3274167 is not a suitable tracer for imaging of OTR in rat brain, probably because of a too low affinity for this receptor in addition to a poor brain penetration. Copyright © 2017 Elsevier Inc. All rights reserved.

Phase feeding in a small-bird production scenario: effect on growth performance, yield, and fillet dimension.

PubMed

Brewer, V B; Owens, C M; Emmert, J L

2012-05-01

Phase feeding (PF) has been effective at maintaining broiler growth while reducing production cost, but the effect on different broiler strains grown in a small-bird production scenario has not been assessed. Three strains of commercial broilers were fed a diet containing average industry nutrient levels from 0 to 18 d. From 18 to 32 d, birds were fed either diets with average industry nutrient levels or diets with phased levels of amino acids. For PF, diets were prepared that contained Lys, sulfur amino acids, and Thr levels matching the predicted requirements for birds at the beginning (high nutrient density) and end (low nutrient density) of PF. Pelleted high and low nutrient-density diets were blended to produce rations containing amino acid levels that matched the predicted PF requirements over 2-d intervals, and diets were switched every other day during PF. Treatments were replicated in 6 pens; each pen contained 15 males and 15 females. Weight gain, feed intake, and feed efficiency were calculated. All birds were commercially processed; yield and fillet dimensions were calculated. Differences among strain BW were noted on d 0, 18, 32, and at processing. Males weighed more than females on d 18 (excluding strain C), 32, and the day of processing. Weight gain was affected by strain (P < 0.05) but not by feeding regimen in the overall growth period (18-39 d). Feed efficiency was improved by PF in strains B and C during the overall growth period. Fillet yield was improved with PF for strain B, and there were no significant differences between PF and industry fillet yields for the other 2 strains. Phase feeding had no effect on fillet dimensions, and there was little effect of strain. These results suggest that different strains may vary in their response to PF, although performance was similar or better in PF birds compared with birds fed the industry diet, regardless of strain.

B-Cell Responses to Pregnancy-Restricted and -Unrestricted Plasmodium falciparum Erythrocyte Membrane Protein 1 Antigens in Ghanaian Women Naturally Exposed to Malaria Parasites

PubMed Central

Ampomah, Paulina; Stevenson, Liz; Ofori, Michael F.; Barfod, Lea

2014-01-01

Protective immunity to Plasmodium falciparum malaria acquired after natural exposure is largely antibody mediated. IgG-specific P. falciparum EMP1 (PfEMP1) proteins on the infected erythrocyte surface are particularly important. The transient antibody responses and the slowly acquired protective immunity probably reflect the clonal antigenic variation and allelic polymorphism of PfEMP1. However, it is likely that other immune-evasive mechanisms are also involved, such as interference with formation and maintenance of immunological memory. We measured PfEMP1-specific antibody levels by enzyme-linked immunosorbent assay (ELISA) and memory B-cell frequencies by enzyme-linked immunosorbent spot (ELISPOT) assay in a cohort of P. falciparum-exposed nonpregnant Ghanaian women. The antigens used were a VAR2CSA-type PfEMP1 (IT4VAR04) with expression restricted to parasites infecting the placenta, as well as two commonly recognized PfEMP1 proteins (HB3VAR06 and IT4VAR60) implicated in rosetting and not pregnancy restricted. This enabled, for the first time, a direct comparison in the same individuals of immune responses specific for a clinically important parasite antigen expressed only during well-defined periods (pregnancy) to responses specific for comparable antigens expressed independent of pregnancy. Our data indicate that PfEMP1-specific B-cell memory is adequately acquired even when antigen exposure is infrequent (e.g., VAR2CSA-type PfEMP1). Furthermore, immunological memory specific for VAR2CSA-type PfEMP1 can be maintained for many years without antigen reexposure and after circulating antigen-specific IgG has disappeared. The study provides evidence that natural exposure to P. falciparum leads to formation of durable B-cell immunity to clinically important PfEMP1 antigens. This has encouraging implications for current efforts to develop PfEMP1-based vaccines. PMID:24566620

Rapid Diagnostic Tests for Malaria Diagnosis in the Peruvian Amazon: Impact of pfhrp2 Gene Deletions and Cross-Reactions

PubMed Central

Maltha, Jessica; Gamboa, Dionicia; Bendezu, Jorge; Sanchez, Luis; Cnops, Lieselotte; Gillet, Philippe; Jacobs, Jan

2012-01-01

Background In the Peruvian Amazon, Plasmodium falciparum and Plasmodium vivax malaria are endemic in rural areas, where microscopy is not available. Malaria rapid diagnostic tests (RDTs) provide quick and accurate diagnosis. However, pfhrp2 gene deletions may limit the use of histidine-rich protein-2 (PfHRP2) detecting RDTs. Further, cross-reactions of P. falciparum with P. vivax-specific test lines and vice versa may impair diagnostic specificity. Methods Thirteen RDT products were evaluated on 179 prospectively collected malaria positive samples. Species diagnosis was performed by microscopy and confirmed by PCR. Pfhrp2 gene deletions were assessed by PCR. Results Sensitivity for P. falciparum diagnosis was lower for PfHRP2 compared to P. falciparum-specific Plasmodium lactate dehydrogenase (Pf-pLDH)- detecting RDTs (71.6% vs. 98.7%, p<0.001). Most (19/21) false negative PfHRP2 results were associated with pfhrp2 gene deletions (25.7% of 74 P. falciparum samples). Diagnostic sensitivity for P. vivax (101 samples) was excellent, except for two products. In 10/12 P. vivax-detecting RDT products, cross-reactions with the PfHRP2 or Pf-pLDH line occurred at a median frequency of 2.5% (range 0%–10.9%) of P. vivax samples assessed. In two RDT products, two and one P. falciparum samples respectively cross-reacted with the Pv-pLDH line. Two Pf-pLDH/pan-pLDH-detecting RDTs showed excellent sensitivity with few (1.0%) cross-reactions but showed faint Pf-pLDH lines in 24.7% and 38.9% of P. falciparum samples. Conclusion PfHRP2-detecting RDTs are not suitable in the Peruvian Amazon due to pfhrp2 gene deletions. Two Pf-pLDH-detecting RDTs performed excellently and are promising RDTs for this region although faint test lines are of concern. PMID:22952633

Relationships between static foot alignment and dynamic plantar loads in runners with acute and chronic stages of plantar fasciitis: a cross-sectional study

PubMed Central

Ribeiro, Ana P.; Sacco, Isabel C. N.; Dinato, Roberto C.; João, Silvia M. A.

2016-01-01

BACKGROUND: The risk factors for the development of plantar fasciitis (PF) have been associated with the medial longitudinal arch (MLA), rearfoot alignment and calcaneal overload. However, the relationships between the biomechanical variables have yet to be determined. OBJECTIVE: The goal of this study was to investigate the relationships between the MLA, rearfoot alignment, and dynamic plantar loads in runners with unilateral PF in acute and chronic phases. METHOD: Cross-sectional study which thirty-five runners with unilateral PF were evaluated: 20 in the acute phase (with pain) and 15 with previous chronic PF (without pain). The MLA index and rearfoot alignment were calculated using digital images. The contact area, maximum force, peak pressure, and force-time integral over three plantar areas were acquired with Pedar X insoles while running at 12 km/h, and the loading rates were calculated from the vertical forces. RESULTS: The multiple regression analyses indicated that both the force-time integral (R 2=0.15 for acute phase PF; R 2=0.17 for chronic PF) and maximum force (R 2=0.35 for chronic PF) over the forefoot were predicted by an elevated MLA index. The rearfoot valgus alignment predicted the maximum force over the rearfoot in both PF groups: acute (R 2=0.18) and chronic (R 2=0.45). The rearfoot valgus alignment also predicted higher loading rates in the PF groups: acute (R 2=0.19) and chronic (R 2=0.40). CONCLUSION: The MLA index and the rearfoot alignment were good predictors of plantar loads over the forefoot and rearfoot areas in runners with PF. However, rearfoot valgus was demonstrated to be an important clinical measure, since it was able to predict the maximum force and both loading rates over the rearfoot. PMID:26786073

Mapping the receptivity of malaria risk to plan the future of control in Somalia

PubMed Central

Alegana, Victor Adagi; Patil, Anand Prabhakar; Moloney, Grainne; Borle, Mohammed; Yusuf, Fahmi; Amran, Jamal; Snow, Robert William

2012-01-01

Objectives To measure the receptive risks of malaria in Somalia and compare decisions on intervention scale-up based on this map and the more widely used contemporary risk maps. Design Cross-sectional community Plasmodium falciparum parasite rate (PfPR) data for the period 2007–2010 corrected to a standard age range of 2 to <10 years (PfPR2–10) and used within a Bayesian space–time geostatistical framework to predict the contemporary (2010) mean PfPR2–10 and the maximum annual mean PfPR2–10 (receptive) from the highest predicted PfPR2–10 value over the study period as an estimate of receptivity. Setting Randomly sampled communities in Somalia. Participants Randomly sampled individuals of all ages. Main outcome measure Cartographic descriptions of malaria receptivity and contemporary risks in Somalia at the district level. Results The contemporary annual PfPR2–10 map estimated that all districts (n=74) and population (n=8.4 million) in Somalia were under hypoendemic transmission (≤10% PfPR2–10). Of these, 23% of the districts, home to 13% of the population, were under transmission of <1% PfPR2–10. About 58% of the districts and 55% of the population were in the risk class of 1% to <5% PfPR2–10. In contrast, the receptivity map estimated 65% of the districts and 69% of the population were under mesoendemic transmission (>10%–50% PfPR2–10) and the rest as hypoendemic. Conclusion Compared with maps of receptive risks, contemporary maps of transmission mask disparities of malaria risk necessary to prioritise and sustain future control. As malaria risk declines across Africa, efforts must be invested in measuring receptivity for efficient control planning. PMID:22855625

Molecular Mechanisms for Drug Hypersensitivity Induced by the Malaria Parasite’s Chloroquine Resistance Transporter

PubMed Central

Baker, Eileen S.; Webster, Michael W.; Lehane, Adele M.; Shafik, Sarah H.; Martin, Rowena E.

2016-01-01

Mutations in the Plasmodium falciparum ‘chloroquine resistance transporter’ (PfCRT) confer resistance to chloroquine (CQ) and related antimalarials by enabling the protein to transport these drugs away from their targets within the parasite’s digestive vacuole (DV). However, CQ resistance-conferring isoforms of PfCRT (PfCRTCQR) also render the parasite hypersensitive to a subset of structurally-diverse pharmacons. Moreover, mutations in PfCRTCQR that suppress the parasite’s hypersensitivity to these molecules simultaneously reinstate its sensitivity to CQ and related drugs. We sought to understand these phenomena by characterizing the functions of PfCRTCQR isoforms that cause the parasite to become hypersensitive to the antimalarial quinine or the antiviral amantadine. We achieved this by measuring the abilities of these proteins to transport CQ, quinine, and amantadine when expressed in Xenopus oocytes and complemented this work with assays that detect the drug transport activity of PfCRT in its native environment within the parasite. Here we describe two mechanistic explanations for PfCRT-induced drug hypersensitivity. First, we show that quinine, which normally accumulates inside the DV and therewithin exerts its antimalarial effect, binds extremely tightly to the substrate-binding site of certain isoforms of PfCRTCQR. By doing so it likely blocks the normal physiological function of the protein, which is essential for the parasite’s survival, and the drug thereby gains an additional killing effect. In the second scenario, we show that although amantadine also sequesters within the DV, the parasite’s hypersensitivity to this drug arises from the PfCRTCQR-mediated transport of amantadine from the DV into the cytosol, where it can better access its antimalarial target. In both cases, the mutations that suppress hypersensitivity also abrogate the ability of PfCRTCQR to transport CQ, thus explaining why rescue from hypersensitivity restores the parasite’s sensitivity to this antimalarial. These insights provide a foundation for understanding clinically-relevant observations of inverse drug susceptibilities in the malaria parasite. PMID:27441371

Effects of stand age and soil properties on soil bacterial and fungal community composition in Chinese pine plantations on the Loess Plateau.

PubMed

Dang, Peng; Yu, Xuan; Le, Hien; Liu, Jinliang; Shen, Zhen; Zhao, Zhong

2017-01-01

The effects of Chinese pine (Pinus tabuliformis) on soil variables after afforestation have been established, but microbial community changes still need to be explored. Using high-throughput sequencing technology, we analyzed bacterial and fungal community composition and diversity in soils from three stands of different-aged, designated 12-year-old (PF1), 29-year-old (PF2), and 53-year-old (PF3), on a Chinese pine plantation and from a natural secondary forest (NSF) stand that was almost 80 years old. Abandoned farmland (BL) was also analyzed. Shannon index values of both bacterial and fungal community in PF1 were greater than those in PF2, PF3 and NSF. Proteobacteria had the lowest abundance in BL, and the abundance increased with stand age. The abundance of Actinobacteria was greater in BL and PF1 soils than those in other sites. Among fungal communities, the dominant taxa were Ascomycota in BL and PF1 and Basidiomycota in PF2, PF3 and NSF, which reflected the successional patterns of fungal communities during the development of Chinese pine plantations. Therefore, the diversity and dominant taxa of soil microbial community in stands 12 and 29 years of age appear to have undergone significant changes; afterward, the soil microbial community achieved a relatively stable state. Furthermore, the abundances of the most dominant bacterial and fungal communities correlated significantly with organic C, total N, C:N, available N, and available P, indicating the dependence of these microbes on soil nutrients. Overall, our findings suggest that the large changes in the soil microbial community structure of Chinese pine plantation forests may be attributed to the phyla present (e.g., Proteobacteria, Actinobacteria, Ascomycota and Basidiomycota) which were affected by soil carbon and nutrients in the Loess Plateau.

Rapid diagnostic tests for malaria diagnosis in the Peruvian Amazon: impact of pfhrp2 gene deletions and cross-reactions.

PubMed

Maltha, Jessica; Gamboa, Dionicia; Bendezu, Jorge; Sanchez, Luis; Cnops, Lieselotte; Gillet, Philippe; Jacobs, Jan

2012-01-01

In the Peruvian Amazon, Plasmodium falciparum and Plasmodium vivax malaria are endemic in rural areas, where microscopy is not available. Malaria rapid diagnostic tests (RDTs) provide quick and accurate diagnosis. However, pfhrp2 gene deletions may limit the use of histidine-rich protein-2 (PfHRP2) detecting RDTs. Further, cross-reactions of P. falciparum with P. vivax-specific test lines and vice versa may impair diagnostic specificity. Thirteen RDT products were evaluated on 179 prospectively collected malaria positive samples. Species diagnosis was performed by microscopy and confirmed by PCR. Pfhrp2 gene deletions were assessed by PCR. Sensitivity for P. falciparum diagnosis was lower for PfHRP2 compared to P. falciparum-specific Plasmodium lactate dehydrogenase (Pf-pLDH)-detecting RDTs (71.6% vs. 98.7%, p<0.001). Most (19/21) false negative PfHRP2 results were associated with pfhrp2 gene deletions (25.7% of 74 P. falciparum samples). Diagnostic sensitivity for P. vivax (101 samples) was excellent, except for two products. In 10/12 P. vivax-detecting RDT products, cross-reactions with the PfHRP2 or Pf-pLDH line occurred at a median frequency of 2.5% (range 0%-10.9%) of P. vivax samples assessed. In two RDT products, two and one P. falciparum samples respectively cross-reacted with the Pv-pLDH line. Two Pf-pLDH/pan-pLDH-detecting RDTs showed excellent sensitivity with few (1.0%) cross-reactions but showed faint Pf-pLDH lines in 24.7% and 38.9% of P. falciparum samples. PfHRP2-detecting RDTs are not suitable in the Peruvian Amazon due to pfhrp2 gene deletions. Two Pf-pLDH-detecting RDTs performed excellently and are promising RDTs for this region although faint test lines are of concern.

CYP-dependent metabolism of PF9601N, a new monoamine oxidase-B inhibitor, by C57BL/6 mouse and human liver microsomes.

PubMed

Dragoni, Stefania; Materozzi, Giada; Pessina, Federica; Frosini, Maria; Marco, José Luis; Unzeta, Mercedes; Sgaragli, Giampietro; Valoti, Massimo

2007-01-01

The selective monoamine oxidase-B (MAO-B) inhibitor, l-deprenyl, is still used for treating Parkinson's patients, however, a disadvantage of its use lies in the formation of l-amphetamine and l-methamphetamine. Subsequently, this has promoted the design of a novel, more potent, MAO-B inhibitor PF9601N, which also has neuroprotective and antioxidant properties. The aim of this work was to investigate the effect of treatment with PF9601N on its own phase I hepatic metabolism. Kinetic parameters of PF9601N CYP-dependent N-dealkylation reaction was also studied and compared with those of l-deprenyl. C57BL/6 mice were treated with PF9601N for 4 days. After CYP content and related monooxygenase activities were assayed in liver microsomes of control and treated animals. CYP activities, cytochrome b5 content, NADPH-cytochrome P450 reductase and various monooxygenase activities were unaffected by in vivo PF9601N treatment. With microsomes from both control and treated mice, the PF9601N-dealkylation product, FA72, was the only detected metabolite with its formation rate following an hyperbolic, Michaelis-Menten curve. Among various inhibitors, only ketoconazole inhibited the FA72 formation rate, indicating a major involvement for CYP3A. Apparent Km and Vmax values generated by human liver microsomes were similar to those found with mouse microsomes. Ketoconazole inhibition indicates that CYP3A is one of the major enzymes involved in PF9601N metabolism also by human liver microsomes. In mouse liver microsomes, the intrinsic clearance of PF9601N was significantly lower than that of l-deprenyl suggestive of an improved bioavailability for the former. The observed favourable metabolic profile may suggest suitability of PF9601N for clinical use.

Clinical Characteristics and Outcomes Are Similar in ARDS Diagnosed by Oxygen Saturation/Fio2 Ratio Compared With Pao2/Fio2 Ratio

PubMed Central

Janz, David R.; Shaver, Ciara M.; Bernard, Gordon R.; Bastarache, Julie A.; Ware, Lorraine B.

2015-01-01

BACKGROUND: Oxygen saturation as measured by pulse oximetry/Fio2 (SF) ratio is highly correlated with the Pao2/Fio2 (PF) ratio in patients with ARDS. However, it remains uncertain whether SF ratio can be substituted for PF ratio for diagnosis of ARDS and whether SF ratio might identify patients who are systemically different from patients diagnosed by PF ratio. METHODS: We conducted a secondary analysis of a large observational prospective cohort study. Patients were eligible if they were admitted to the medical ICU and fulfilled the Berlin definition of ARDS with hypoxemia criteria using either the standard PF threshold (PF ratio ≤ 300) or a previously published SF threshold (SF ratio ≤ 315). RESULTS: Of 362 patients with ARDS, 238 (66%) received a diagnosis by PF ratio and 124 (34%) by SF ratio. In a small group of patients who received diagnoses of ARDS by SF ratio who had arterial blood gas measurements on the same day (n = 10), the PF ratio did not meet ARDS criteria. There were no major differences in clinical characteristics or comorbidities between groups with the exception of APACHE (Acute Physiology and Chronic Health Evaluation) II scores, which were higher in the group diagnosed by PF ratio. However, this difference was no longer apparent when arterial blood gas-dependent variables (pH, Pao2) were removed from the APACHE II score. There were also no differences in clinical outcomes including duration of mechanical ventilation (mean, 7 days in both groups; P = .25), duration of ICU stay (mean, 10 days vs 9 days in PF ratio vs SF ratio; P = .26), or hospital mortality (36% in both groups, P = .9). CONCLUSIONS: Patients with ARDS diagnosed by SF ratio have very similar clinical characteristics and outcomes compared with patients diagnosed by PF ratio. These findings suggest that SF ratio could be considered as a diagnostic tool for early enrollment into clinical trials. PMID:26271028

Half a grid is better than no grid: competition between 2,2':6',2''-terpyridine and 3,6-di(pyrid-2-yl)pyridazine for copper(II).

PubMed

Constable, Edwin C; Decurtins, Silvio; Housecroft, Catherine E; Keene, Tony D; Palivan, Cornelia G; Price, Jason R; Zampese, Jennifer A

2010-03-07

The reaction between Cu(NO(3))(2).3H(2)O, 2,2':6',2''-terpyridine (tpy) and 3,6-di(pyrid-2-yl)pyridazine (1) in a 2 : 2 : 1 molar equivalent ratio in aqueous MeCN in the presence of excess NH(4)PF(6) leads to competition between the assembly of the dinuclear half-grid [Cu(2)(1)(tpy)(2)][PF(6)](4).2H(2)O and the mononuclear complex [Cu(1)(2)(OH(2))][PF(6)](2). The yield of [Cu(2)(1)(tpy)(2)][PF(6)](4).2H(2)O has been optimized using microwave conditions. [Cu(1)(2)(OH(2))][PF(6)](2) can be selectively produced by treating Cu(NO(3))(2).3H(2)O with 1 (1 : 2 molar equivalents) in aqueous MeCN in the presence of NH(4)PF(6). The single crystal structures of [Cu(2)(1)(tpy)(2)][PF(6)](4).4MeNO(2) and [Cu(1)(2)(OH(2))][PF(6)](2) are presented. In the [Cu(2)(1)(tpy)(2)](4+) cation, ligand 1 bridges the two copper(II) centres, each of which is further coordinated by a tpy ligand. The copper(II) coordination geometry is closely associated with the arrangement of the two tpy ligands which engage in efficient face-to-face pi-stacking. Magnetic data for crystalline [Cu(2)(1)(tpy)(2)][PF(6)](4).4MeNO(2) are consistent with a weak antiferromagnetic interaction between the two copper(II) centres. EPR spectroscopic data for a powder sample of [Cu(2)(1)(tpy)(2)][PF(6)](4).2H(2)O are consistent with the dinuclear structure, but in frozen DMF and DMSO solutions, the data indicate that the dinuclear structure of [Cu(2)(1)(tpy)(2)](4+) is not preserved.

Recognition and binding of the PF2 lectin to α-amylase from Zabrotes subfasciatus (Coleoptera:Bruchidae) larval midgut.

PubMed

Lagarda-Diaz, I; Geiser, D; Guzman-Partida, A M; Winzerling, J; Vazquez-Moreno, L

2014-01-01

Amylases are an important family of enzymes involved in insect carbohydrate metabolism that are required for the survival of insect larvae. For this reason, enzymes from starch-dependent insects are targets for insecticidal control. PF2 (Olneya tesota) is a lectin that is toxic to Zabrotes subfasciatus (Coleoptera: Bruchidae) larvae. In this study, we evaluated recognition of the PF2 lectin to α-amylases from Z. subfasciatus midgut and the effect of PF2 on α-amylase activity. PF2 caused a decrease of total amylase activity in vitro. Subsequently, several α-amylase isoforms were isolated from insect midgut tissues using ion exchange chromatography. Three enzyme isoforms were verified by an in-gel assay for amylase activity; however, only one isoform was recognized by antiamylase serum and PF2. The identity of this Z. subfasciatus α-amylase was confirmed by liquid chromatography-tandem mass spectrometry. The findings strongly suggest that a glycosylated α-amylase isoform from larval Z. subfasciatus midgut interacts with PF2, which interferes with starch digestion. © The Author 2014. Published by Oxford University Press on behalf of the Entomological Society of America.

Studies on structural, thermal and AC conductivity scaling of PEO-LiPF6 polymer electrolyte with added ionic liquid [BMIMPF6

NASA Astrophysics Data System (ADS)

Chaurasia, S. K.; Saroj, A. L.; Shalu, Singh, V. K.; Tripathi, A. K.; Gupta, A. K.; Verma, Y. L.; Singh, R. K.

2015-07-01

Preparation and characterization of polymer electrolyte films of PEO+10wt.% LiPF6 + xwt.% BMIMPF6 (1-butyl-3-methylimidazolium hexafluorophosphate) containing dopant salt lithium hexafluorophosphate (LiPF6) and ionic liquid (BMIMPF6) having common anion PF6 - are reported. The ionic conductivity of the polymer electrolyte films has been found to increase with increasing concentration of BMIMPF6 in PEO+10 wt.% LiPF6 due to the plasticization effect of ionic liquid. DSC and XRD results show that the crystallinity of polymer electrolyte decreases with BMIMPF6 concentration which, in turn, is responsible for the increase in ionic conductivity. FTIR spectroscopic study shows the complexation of salt and/or ionic liquid cations with the polymer backbone. Ion dynamics behavior of PEO+LiPF6 as well as PEO+LiPF6 + BMIMPF6 polymer electrolytes was studied by frequency dependent conductivity, σ(f) measurements. The values σ(f) at various temperatures have been analyzed in terms of Jonscher power law (JPL) and scaled with respect to frequency which shows universal power law characteristics at all temperatures.

Efflux of a range of antimalarial drugs and 'chloroquine resistance reversers' from the digestive vacuole in malaria parasites with mutant PfCRT.

PubMed

Lehane, Adele M; Kirk, Kiaran

2010-08-01

Chloroquine-resistant malaria parasites (Plasmodium falciparum) show an increased leak of H(+) ions from their internal digestive vacuole in the presence of chloroquine. This phenomenon has been attributed to the transport of chloroquine, together with H(+), out of the digestive vacuole (and hence away from its site of action) via a mutant form of the parasite's chloroquine resistance transporter (PfCRT). Here, using transfectant parasite lines, we show that a range of other antimalarial drugs, as well as various 'chloroquine resistance reversers' induce an increased leak of H(+) from the digestive vacuole of parasites expressing mutant PfCRT, consistent with these compounds being substrates for mutant forms, but not the wild-type form, of PfCRT. For some compounds there were significant differences observed between parasites having the African/Asian Dd2 form of PfCRT and those with the South American 7G8 form of PfCRT, consistent with there being differences in the transport properties of the two mutant proteins. The finding that chloroquine resistance reversers are substrates for mutant PfCRT has implications for the mechanism of action of this class of compound. © 2010 Blackwell Publishing Ltd.

A cross-species translational pharmacokinetic-pharmacodynamic evaluation of core body temperature reduction by the TRPM8 blocker PF-05105679.

PubMed

Gosset, James R; Beaumont, Kevin; Matsuura, Tomomi; Winchester, Wendy; Attkins, Neil; Glatt, Sophie; Lightbown, Ian; Ulrich, Kristina; Roberts, Sonia; Harris, Jolie; Mesic, Emir; van Steeg, Tamara; Hijdra, Diana; van der Graaf, Piet H

2017-11-15

PF-05105679 is a moderately potent TRPM8 blocker which has been evaluated for the treatment of cold pain sensitivity. The TRPM8 channel is responsible for the sensation of cold environmental temperatures and has been implicated in regulation of core body temperature. Consequently, blockade of TRPM8 has been suggested to result in lowering of core body temperature. As part of the progression to human studies, the effect of PF-05105679 on core body temperature has been investigated in animals. Safety pharmacology studies showed that PF-05105679 reduced core body temperature in a manner that was inversely related to body weight of the species tested (greater exposure to PF-05105679 was required to lower temperature by 1°C in higher species). Based on an allometric (body weight) relationship, it was hypothesized that PF-05105679 would not lower core body temperature in humans at exposures that could exhibit pharmacological effects on cold pain sensation. On administration to humans, PF-05105679 was indeed effective at reversing the cold pain sensation associated with the cold pressor test in the absence of effects on core body temperature. Copyright © 2017 Elsevier B.V. All rights reserved.

Study of the interrelation between the electrotechnical parameters of the plasma focus discharge circuit and the plasma compression dynamics on the PF-3 and PF-1000 facilities

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

Mitrofanov, K. N., E-mail: mitrkn@inbox.ru; Krauz, V. I., E-mail: krauz-vi@nrcki.ru, E-mail: vkrauz@yandex.ru; Grabovski, E. V.

The main stages of the plasma current sheath (PCS) dynamics on two plasma focus (PF) facilities with different geometries of the electrode system, PF-3 (Filippov type) and PF-1000 (Mather type), were studied by analyzing the results of the current and voltage measurements. Some dynamic characteristics, such as the PCS velocity in the acceleration phase in the Mather-type facility (PF-1000), the moment at which the PCS reaches the anode end, and the plasma velocity in the radial stage of plasma compression in the PF-3 Filippov-type facility, were determined from the time dependence of the inductance of the discharge circuit with amore » dynamic plasma load. The energy characteristics of the discharge circuit of the compressing PCS were studied for different working gases (deuterium, argon, and neon) at initial pressures of 1.5–3 Torr in discharges with energies of 0.3–0.6 MJ. In experiments with deuterium, correlation between the neutron yield and the electromagnetic energy deposited directly in the compressed PCS was investigated.« less

Impact of Antarctic Polar Front Variability on Southern Ocean Biogeochemistry

NASA Astrophysics Data System (ADS)

Freeman, N. M.; Lovenduski, N. S.; Gent, P. R.

2016-12-01

The Antarctic Polar Front (PF) is an important biogeochemical divide in the Southern Ocean, often coinciding with sharp gradients in silicate and nitrate concentration at the surface. Variability in the PF has the potential to influence Southern Ocean biogeochemistry and biological productivity both locally and at the basin scale. Characterizing PF variability is important for contextualizing recent biogeochemical observations from ORCAS, SOCCOM, and the Drake Passage time-series, as well as for understanding how anthropogenic change is influencing Southern Ocean biogeochemistry. Here, we employ a suite of remote sensing observations and output from the Community Earth System Model (CESM) to better understand the relationship between the PF and local biogeochemistry in the Southern Ocean. Using microwave SST measurements spanning 2002-2014 that avoid cloud contamination, we show that the PF has shifted northward (southward) in the Pacific (Indian) sector and intensified at nearly all longitudes along its circumpolar path. We identify the PF in CESM at both coarse (1°x1°) and fine (0.1°x0.1°) horizontal resolutions using temperature and silicate gradient maxima, and quantify its spatial and temporal variability. We further investigate co-variance between the position and intensity of the PF and local phytoplankton community structure.

A.C. impedance, XRD, DSC, SEM and charge/discharge studies on Al2O3, TiO2, SiO2 dispersoid LiPF6/PVC/PVdF-co-HFP composite polymer electrolytes by phase inversion

NASA Astrophysics Data System (ADS)

Vickraman, P.; Gopukumar, S.

2017-07-01

The PVC/PVdF-co-HFP composite polymer electrolyte membranes (CPEMs) by varying blend ratios 1:1, 1:2, and 2:1 with fixed content of Al2O3, TiO2 and SiO2 having soaked in 0.5 M LiPF6 in EC/DEC (1:1) v/v) have been prepared by phase inversion. CPEMs of higher ionic conductivity (not dependent on electrolyte uptake as observed in our study) ASA4 (3.61×10-4 Scm-1), TSA3 (1.53×10-4 Scm-1), and SSA3 (4.81×10-4 Scm-1) have been only chosen for XRD, DSC, SEM and electrochemical studies. In XRD, crystalline peaks (phases) of PVdF have been noted with/without change in intensity as well as FWHM which correspond to type of filler interaction with host matrix. In DSC, it is observed that shifts in baseline, melting endotherms, and area under the endotherms indicating the thermal hist ory of PVC (Tg = 82 ° C) and melting of VdF crystallites varied with nature of the filler dispersoid. In SEM, the coagulated fibrils of the polymer coiled with the sponge like structure has been mapped. The charge/discharge studies are carried out on these CPEMs at C/10 rate in the voltage range 2.8 V - 4.2 V, and it is noted that the TSA3 showed better cycling performance with good capacity retention i.e., 50 cycles with 66% capacity retention than ASA4 of 28 cycles with 65% and SSA3 of 5 cycles with 56%. In the present study Coulombic efficiency is concerned only for first cycle and it is noted that the TSA3 showed 71% than 66% and 62% respectively for SSA3 and ASA4.

49 CFR 178.356 - Specification 20PF phenolic-foam insulated, metal overpack.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 3 2011-10-01 2011-10-01 false Specification 20PF phenolic-foam insulated, metal overpack. 178.356 Section 178.356 Transportation Other Regulations Relating to Transportation (Continued... Specification 20PF phenolic-foam insulated, metal overpack. ...

49 CFR 178.356 - Specification 20PF phenolic-foam insulated, metal overpack.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Specification 20PF phenolic-foam insulated, metal overpack. 178.356 Section 178.356 Transportation Other Regulations Relating to Transportation PIPELINE AND... Specification 20PF phenolic-foam insulated, metal overpack. ...

Electrically heated particulate filter embedded heater design

DOEpatents

Gonze, Eugene V.; Chapman, Mark R.

2014-07-01

An exhaust system that processes exhaust generated by an engine is provided. The system generally includes a particulate filter (PF) that filters particulates from the exhaust wherein an upstream end of the PF receives exhaust from the engine and wherein an upstream surface of the particulate filter includes machined grooves. A grid of electrically resistive material is inserted into the machined grooves of the exterior upstream surface of the PF and selectively heats exhaust passing through the grid to initiate combustion of particulates within the PF.

The tridimensional geometry of the proximal femur should determine the design of cementless femoral stem in total hip arthroplasty.

PubMed

Wegrzyn, Julien; Roux, Jean-Paul; Loriau, Charlotte; Bonin, Nicolas; Pibarot, Vincent

2018-02-22

Using a cementless femoral stem in total hip arthroplasty (THA), optimal filling of the proximal femoral metaphyseal volume (PFMV) and restoration of the extramedullary proximal femoral (PF) parameters (i.e., femoral offset (FO), neck length (FNL), and head height (FHH)) constitute key goals for optimal hip biomechanics, functional outcome, and THA survivorship. However, almost 30% of mismatch between the PF anatomy and implant geometry of the most widely implanted non-modular cementless femoral stem has been demonstrated in a computed tomography scan (CT scan) study. Therefore, this anatomic study aimed to evaluate the relationship between the intra- and extramedullary PF parameters using tridimensional CT scan reconstructions. One hundred fifty-one CT scans of adult healthy hips were obtained from 151 male Caucasian patients (mean age = 66 ± 11 years) undergoing lower limb CT scan arteriography. Tridimensional PF reconstructions and parameter measurements were performed using a corrected PF coronal plane-defined by the femoral neck and diaphyseal canal longitudinal axes-to avoid influence of PF helitorsion and femoral neck version on extramedullary PF parameters. Independently of the femoral neck-shaft angle, the PFMV was significantly and positively correlated with the FO, FNL, and FHH (r = 0.407 to 0.420; p < 0.0001). This study emphasized that the tridimensional PF geometry measurement in the corrected coronal plane of the femoral neck can be useful to determine and optimize the design of a non-modular cementless femoral stem. Particularly, continuous homothetic size progression of the intra- and extramedullary PF parameters should be achieved to assure stem fixation and restore anatomic hip biomechanics.

An Interspecies Signaling System Mediated by Fusaric Acid Has Parallel Effects on Antifungal Metabolite Production by Pseudomonas protegens Strain Pf-5 and Antibiosis of Fusarium spp.

PubMed

Quecine, Maria Carolina; Kidarsa, Teresa A; Goebel, Neal C; Shaffer, Brenda T; Henkels, Marcella D; Zabriskie, T Mark; Loper, Joyce E

2015-12-11

Pseudomonas protegens strain Pf-5 is a rhizosphere bacterium that suppresses soilborne plant diseases and produces at least seven different secondary metabolites with antifungal properties. We derived mutants of Pf-5 with single and multiple mutations in biosynthesis genes for seven antifungal metabolites: 2,4-diacetylphoroglucinol (DAPG), pyrrolnitrin, pyoluteorin, hydrogen cyanide, rhizoxin, orfamide A, and toxoflavin. These mutants were tested for inhibition of the pathogens Fusarium verticillioides and Fusarium oxysporum f. sp. pisi. Rhizoxin, pyrrolnitrin, and DAPG were found to be primarily responsible for fungal antagonism by Pf-5. Previously, other workers showed that the mycotoxin fusaric acid, which is produced by many Fusarium species, including F. verticillioides, inhibited the production of DAPG by Pseudomonas spp. In this study, amendment of culture media with fusaric acid decreased DAPG production, increased pyoluteorin production, and had no consistent influence on pyrrolnitrin or orfamide A production by Pf-5. Fusaric acid also altered the transcription of biosynthetic genes, indicating that the mycotoxin influenced antibiotic production by Pf-5 at the transcriptional level. Addition of fusaric acid to the culture medium reduced antibiosis of F. verticillioides by Pf-5 and derivative strains that produce DAPG but had no effect on antibiosis by Pf-5 derivatives that suppressed F. verticillioides due to pyrrolnitrin or rhizoxin production. Our results demonstrated the importance of three compounds, rhizoxin, pyrrolnitrin, and DAPG, in suppression of Fusarium spp. by Pf-5 and confirmed that an interspecies signaling system mediated by fusaric acid had parallel effects on antifungal metabolite production and antibiosis by the bacterial biological control organism. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Restless legs syndrome status as a predictor for lower physical function

PubMed Central

Zhang, Chunbai; Li, Yanping; Malhotra, Atul; Ning, Yi

2014-01-01

Objective: To examine the potential long-term impact of restless legs syndrome (RLS) and other common sleep complaints on subsequent physical function (PF), we conducted a longitudinal analysis of 12,556 men in the Health Professionals Follow-up Study. Methods: We used a set of questions recommended by the International RLS Study Group to assess RLS in 2002. We asked questions regarding other sleep complaints—insomnia, sleep fragmentation, and excessive daytime sleepiness—in 2004. We used the Physical Function (PF-10) survey of the Short Form–36 Health Survey to characterize PF in 1996 and 2008. We examined the 2008 PF-10 scores across categories of baseline RLS (2002), adjusted for age, 1996 PF-10 score, and other potential confounders. Results: The participants with RLS at baseline had significantly lower PF-10 score 6 years later than those without RLS (mean difference = −2.32, p = 0.01), after adjusting for potential confounders. The magnitude of difference in PF-10 score for RLS symptoms ≥15 times/month vs no RLS was more than that of a 5-year increase of age or moderate amount of smoking. Having daily daytime sleepiness and sleep duration ≥9 hours/day were associated with lower mean PF value than not having these symptoms (p < 0.05 for both). Conclusions: RLS and other sleep complaints are associated with lower PF. Our findings need to be replicated by more longitudinal studies including women and populations of other social and cultural backgrounds. It is important to understand whether RLS is an independent risk factor or a marker for other unknown risk factors for disability. PMID:24598708

Physical function metric over measure: An illustration with the Patient-Reported Outcomes Measurement Information System (PROMIS) and the Functional Assessment of Cancer Therapy (FACT).

PubMed

Kaat, Aaron J; Schalet, Benjamin D; Rutsohn, Joshua; Jensen, Roxanne E; Cella, David

2018-01-01

Measuring patient-reported outcomes (PROs) is becoming an integral component of quality improvement initiatives, clinical care, and research studies in cancer, including comparative effectiveness research. However, the number of PROs limits comparability across studies. Herein, the authors attempted to link the Functional Assessment of Cancer Therapy-General Physical Well-Being (FACT-G PWB) subscale with the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) calibrated item bank. The also sought to augment a subset of the conceptually most similar FACT-G PWB items with PROMIS PF items to improve the linking. Baseline data from 5506 participants in the Measuring Your Health (MY-Health) study were used to identify the optimal items for linking FACT-G PWB with PROMIS PF. A mixed methods approach identified the optimal items for creating the 5-item FACT/PROMIS-PF5 scale. Both the linked and augmented relationships were cross-validated using the follow-up MY-Health data. A 5-item FACT-G PWB item subset was found to be optimal for linking with PROMIS PF. In addition, a 2-item subset, including only items that were conceptually very similar to the PROMIS item bank content, were augmented with 3 PROMIS PF items. This new FACT/PROMIS-PF5 provided superior score recovery. The PROMIS PF metric allows for the evaluation of the extent to which similar questionnaires can be linked and therefore expressed on the same metric. These results allow for the aggregation of existing data and provide an optimal measure for future studies wishing to use the FACT yet also report on the PROMIS PF metric. Cancer 2018;124:153-60. © 2017 American Cancer Society. © 2017 American Cancer Society.

An Interspecies Signaling System Mediated by Fusaric Acid Has Parallel Effects on Antifungal Metabolite Production by Pseudomonas protegens Strain Pf-5 and Antibiosis of Fusarium spp.

PubMed Central

Quecine, Maria Carolina; Kidarsa, Teresa A.; Goebel, Neal C.; Shaffer, Brenda T.; Henkels, Marcella D.; Zabriskie, T. Mark

2015-01-01

Pseudomonas protegens strain Pf-5 is a rhizosphere bacterium that suppresses soilborne plant diseases and produces at least seven different secondary metabolites with antifungal properties. We derived mutants of Pf-5 with single and multiple mutations in biosynthesis genes for seven antifungal metabolites: 2,4-diacetylphoroglucinol (DAPG), pyrrolnitrin, pyoluteorin, hydrogen cyanide, rhizoxin, orfamide A, and toxoflavin. These mutants were tested for inhibition of the pathogens Fusarium verticillioides and Fusarium oxysporum f. sp. pisi. Rhizoxin, pyrrolnitrin, and DAPG were found to be primarily responsible for fungal antagonism by Pf-5. Previously, other workers showed that the mycotoxin fusaric acid, which is produced by many Fusarium species, including F. verticillioides, inhibited the production of DAPG by Pseudomonas spp. In this study, amendment of culture media with fusaric acid decreased DAPG production, increased pyoluteorin production, and had no consistent influence on pyrrolnitrin or orfamide A production by Pf-5. Fusaric acid also altered the transcription of biosynthetic genes, indicating that the mycotoxin influenced antibiotic production by Pf-5 at the transcriptional level. Addition of fusaric acid to the culture medium reduced antibiosis of F. verticillioides by Pf-5 and derivative strains that produce DAPG but had no effect on antibiosis by Pf-5 derivatives that suppressed F. verticillioides due to pyrrolnitrin or rhizoxin production. Our results demonstrated the importance of three compounds, rhizoxin, pyrrolnitrin, and DAPG, in suppression of Fusarium spp. by Pf-5 and confirmed that an interspecies signaling system mediated by fusaric acid had parallel effects on antifungal metabolite production and antibiosis by the bacterial biological control organism. PMID:26655755

The chitinase PfCHT1 from the human malaria parasite Plasmodium falciparum lacks proenzyme and chitin-binding domains and displays unique substrate preferences.

PubMed

Vinetz, J M; Dave, S K; Specht, C A; Brameld, K A; Xu, B; Hayward, R; Fidock, D A

1999-11-23

Within hours after the ingestion of a blood meal, the mosquito midgut epithelium synthesizes a chitinous sac, the peritrophic matrix. Plasmodium ookinetes traverse the peritrophic matrix while escaping the mosquito midgut. Chitinases (EC 3.2.1.14) are critical for parasite invasion of the midgut: the presence of the chitinase inhibitor, allosamidin, in an infectious blood meal prevents oocyst development. A chitinase gene, PgCHT1, recently has been identified in the avian malaria parasite P. gallinaceum. We used the sequence of PgCHT1 to identify a P. falciparum chitinase gene, PfCHT1, in the P. falciparum genome database. PfCHT1 differs from PgCHT1 in that the P. falciparum gene lacks proenzyme and chitin-binding domains. PfCHT1 was expressed as an active recombinant enzyme in Escherichia coli. PfCHT1 shares with PgCHT1 a substrate preference unique to Plasmodium chitinases: the enzymes cleave tri- and tetramers of GlcNAc from penta- and hexameric oligomers and are unable to cleave smaller native chitin oligosaccharides. The pH activity profile of PfCHT1 and its IC(50) (40 nM) to allosamidin are distinct from endochitinase activities secreted by P. gallinaceum ookinetes. Homology modeling predicts that PgCHT1 has a novel pocket in the catalytic active site that PfCHT1 lacks, which may explain the differential sensitivity of PfCHT1 and PgCHT1 to allosamidin. PfCHT1 may be the ortholog of a second, as yet unidentified, chitinase gene of P. gallinaceum. These results may allow us to develop novel strategies of blocking human malaria transmission based on interfering with P. falciparum chitinase.

The chitinase PfCHT1 from the human malaria parasite Plasmodium falciparum lacks proenzyme and chitin-binding domains and displays unique substrate preferences

PubMed Central

Vinetz, Joseph M.; Dave, Sanat K.; Specht, Charles A.; Brameld, Kenneth A.; Xu, Bo; Hayward, Rhian; Fidock, David A.

1999-01-01

Within hours after the ingestion of a blood meal, the mosquito midgut epithelium synthesizes a chitinous sac, the peritrophic matrix. Plasmodium ookinetes traverse the peritrophic matrix while escaping the mosquito midgut. Chitinases (EC 3.2.1.14) are critical for parasite invasion of the midgut: the presence of the chitinase inhibitor, allosamidin, in an infectious blood meal prevents oocyst development. A chitinase gene, PgCHT1, recently has been identified in the avian malaria parasite P. gallinaceum. We used the sequence of PgCHT1 to identify a P. falciparum chitinase gene, PfCHT1, in the P. falciparum genome database. PfCHT1 differs from PgCHT1 in that the P. falciparum gene lacks proenzyme and chitin-binding domains. PfCHT1 was expressed as an active recombinant enzyme in Escherichia coli. PfCHT1 shares with PgCHT1 a substrate preference unique to Plasmodium chitinases: the enzymes cleave tri- and tetramers of GlcNAc from penta- and hexameric oligomers and are unable to cleave smaller native chitin oligosaccharides. The pH activity profile of PfCHT1 and its IC50 (40 nM) to allosamidin are distinct from endochitinase activities secreted by P. gallinaceum ookinetes. Homology modeling predicts that PgCHT1 has a novel pocket in the catalytic active site that PfCHT1 lacks, which may explain the differential sensitivity of PfCHT1 and PgCHT1 to allosamidin. PfCHT1 may be the ortholog of a second, as yet unidentified, chitinase gene of P. gallinaceum. These results may allow us to develop novel strategies of blocking human malaria transmission based on interfering with P. falciparum chitinase. PMID:10570198

The median preoptic nucleus reciprocally modulates activity of arousal-related and sleep-related neurons in the perifornical lateral hypothalamus.

PubMed

Suntsova, Natalia; Guzman-Marin, Ruben; Kumar, Sunil; Alam, Md Noor; Szymusiak, Ronald; McGinty, Dennis

2007-02-14

The perifornical-lateral hypothalamic area (PF/LH) contains neuronal groups playing an important role in control of waking and sleep. Among the brain regions that regulate behavioral states, one of the strongest sources of projections to the PF/LH is the median preoptic nucleus (MnPN) containing a sleep-active neuronal population. To evaluate the role of MnPN afferents in the control of PF/LH neuronal activity, we studied the responses of PF/LH cells to electrical stimulation or local chemical manipulation of the MnPN in freely moving rats. Single-pulse electrical stimulation evoked responses in 79% of recorded PF/LH neurons. No cells were activated antidromically. Direct and indirect transsynaptic effects depended on sleep-wake discharge pattern of PF/LH cells. The majority of arousal-related neurons, that is, cells discharging at maximal rates during active waking (AW) or during AW and rapid eye movement (REM) sleep, exhibited exclusively or initially inhibitory responses to stimulation. Sleep-related neurons, the cells with elevated discharge during non-REM and REM sleep or selectively active in REM sleep, exhibited exclusively or initially excitatory responses. Activation of the MnPN via microdialytic application of L-glutamate or bicuculline resulted in reduced discharge of arousal-related and in excitation of sleep-related PF/LH neurons. Deactivation of the MnPN with muscimol caused opposite effects. The results indicate that the MnPN contains subset(s) of neurons, which exert inhibitory control over arousal-related and excitatory control over sleep-related PF/LH neurons. We hypothesize that MnPN sleep-active neuronal group has both inhibitory and excitatory outputs that participate in the inhibitory control of arousal-promoting PF/LH mechanisms.

Microarray Analysis and Mutagenesis of the Biological Control Agent Pseudomonas fluorescens Pf-5

USDA-ARS?s Scientific Manuscript database

The biological control agent Pseudomonas fluorescens Pf-5 suppresses seedling emergence diseases caused by soilborne fungi and Oomycetes. Pf-5 produces at least ten secondary metabolites. These include hydrogen cyanide, pyrrolnitrin, pyoluteorin and 2,4-diacetylphloroglucinol, which have known funct...

PF-06827443 Displays Robust Allosteric Agonist and Positive Allosteric Modulator Activity in High Receptor Reserve and Native Systems.

PubMed

Moran, Sean P; Cho, Hyekyung P; Maksymetz, James; Remke, Daniel H; Hanson, Ryan M; Niswender, Colleen M; Lindsley, Craig W; Rook, Jerri M; Conn, P Jeffrey

2018-04-25

Positive allosteric modulators (PAMs) of the M 1 subtype of muscarinic acetylcholine receptor have attracted intense interest as an exciting new approach for improving the cognitive deficits in schizophrenia and Alzheimer's disease. Recent evidence suggests that the presence of intrinsic agonist activity of some M 1 PAMs may reduce efficacy and contribute to adverse effect liability. However, the M 1 PAM PF-06827443 was reported to have only weak agonist activity at human M 1 receptors but produced M 1 -dependent adverse effects. We now report that PF-06827443 is an allosteric agonist in cell lines expressing rat, dog, and human M 1 and use of inducible cell lines shows that agonist activity of PF-06827443 is dependent on receptor reserve. Furthermore, PF-06827443 is an agonist in native tissue preparations and induces behavioral convulsions in mice similar to other ago-PAMs. These findings suggest that PF-06827443 is a robust ago-PAM, independent of species, in cell lines and native systems.

Structural basis of malaria parasite lysyl-tRNA synthetase inhibition by cladosporin.

PubMed

Khan, Sameena; Sharma, Arvind; Belrhali, Hassan; Yogavel, Manickam; Sharma, Amit

2014-06-01

Malaria parasites inevitably develop drug resistance to anti-malarials over time. Hence the immediacy for discovering new chemical scaffolds to include in combination malaria drug therapy. The desirable attributes of new chemotherapeutic agents currently include activity against both liver and blood stage malaria parasites. One such recently discovered compound called cladosporin abrogates parasite growth via inhibition of Plasmodium falciparum lysyl-tRNA synthetase (PfKRS), an enzyme central to protein translation. Here, we present crystal structure of ternary PfKRS-lysine-cladosporin (PfKRS-K-C) complex that reveals cladosporin's remarkable ability to mimic the natural substrate adenosine and thereby colonize PfKRS active site. The isocoumarin fragment of cladosporin sandwiches between critical adenine-recognizing residues while its pyran ring fits snugly in the ribose-recognizing cavity. PfKRS-K-C structure highlights ample space within PfKRS active site for further chemical derivatization of cladosporin. Such derivatives may be useful against additional human pathogens that retain high conservation in cladosporin chelating residues within their lysyl-tRNA synthetase.

Discovery of a highly selective glycogen synthase kinase-3 inhibitor (PF-04802367) that modulates tau phosphorylation in brain: Translation for PET neuroimaging

PubMed Central

Liang, Steven H.; Chen, Jinshan Michael; Normandin, Marc D.; Chang, Jeanne S.; Chang, George C.; Taylor, Christine K.; Trapa, Patrick; Plummer, Mark S.; Para, Kimberly S.; Conn, Edward L.; Lopresti-Morrow, Lori; Lanyon, Lorraine F.; Cook, James M.; Richter, Karl E. G.; Nolan, Charlie E.; Schachter, Joel B.; Janat, Fouad; Che, Ye; Shanmugasundaram, Veerabahu; Lefker, Bruce A.; Enerson, Bradley E.; Livni, Elijahu; Wang, Lu; Guehl, Nicolas; Patnaik, Debasis; Wagner, Florence F.; Perlis, Roy; Holson, Edward B.; Haggarty, Stephen J.; Fakhri, Georges El

2016-01-01

Glycogen synthase kinase-3 (GSK-3) regulates multiple cellular processes in diabetes, oncology and neurology. We have identified N-(3-(1H-1,2,4-triazol-1-yl)propyl)-5-(3-chloro-4-methoxyphenyl)oxazole-4-carboxamide (PF-04802367 or PF-367) as a highly potent inhibitor, which is among the most selective antagonists of GSK-3 to date. We demonstrated its efficacy in modulation of tau phosphorylation in vitro and in vivo. Whereas the kinetics of PF-367 binding in brain tissues are too fast for an effective therapeutic agent, the pharmacokinetic profile of PF-367 is ideal for discovery of radiopharmaceuticals for GSK-3 in the central nervous system. A 11C-isotopologue of PF-367 was synthesized and preliminary PET imaging studies in non-human primates confirmed that we have overcome the two major obstacles for imaging GSK-3, namely, reasonable brain permeability and displaceable binding. PMID:27355874

24-Hour Efficacy and Ocular Surface Health with Preservative-Free Tafluprost Alone and in Conjunction with Preservative-Free Dorzolamide/Timolol Fixed Combination in Open-Angle Glaucoma Patients Insufficiently Controlled with Preserved Latanoprost Monotherapy.

PubMed

Konstas, Anastasios-Georgios; Boboridis, Konstadinos G; Kapis, Paraskevas; Marinopoulos, Konstantinos; Voudouragkaki, Irini C; Panayiotou, Dimitrios; Mikropoulos, Dimitrios G; Pagkalidou, Eirini; Haidich, Anna-Bettina; Katsanos, Andreas; Quaranta, Luciano

2017-01-01

The aim of the present study was to evaluate the 24-h efficacy, tolerability, and ocular surface health with preservative-free (PF) tafluprost and a PF triple drug regimen comprising tafluprost and dorzolamide/timolol fixed combination (DTFC) in open-angle glaucoma patients who were insufficiently controlled with preserved branded or generic latanoprost monotherapy and who exhibited signs or symptoms of ocular surface disease (OSD). Prospective, observer-masked, crossover, comparison. Eligible consecutive open-angle glaucoma patients were randomized to either PF tafluprost or the triple PF regimen for 3 months. They were then crossed over to the opposite therapy for another 3 months. At the end of the latanoprost run-in period and after each PF treatment period, patients underwent habitual 24-h intraocular pressure (IOP) monitoring with Goldmann tonometry in the sitting position (at 10:00, 14:00, 18:00, and 22:00) and Perkins tonometry in the supine position (at 02:00 and 06:00). Tolerability and selected ocular surface parameters were evaluated at baseline and the end of each treatment period. Forty-three open-angle glaucoma patients completed the trial. Mean 24-h IOP on preserved latanoprost was 22.2 ± 3.9 mmHg. Compared with latanoprost monotherapy, PF tafluprost obtained a greater reduction in mean, peak, and fluctuation of 24-h IOP including the 02:00 and 06:00 time points (P < 0.05). With the exception of 24-h fluctuation, the triple PF regimen provided significantly lower IOP parameters than latanoprost or PF tafluprost (P < 0.001). Finally, PF tafluprost therapy displayed significantly improved tear film break-up times (6.7 vs 6.0 s), corneal staining (1.3 vs 2.2), and Schirmer I test results (9.1 vs 8.2 mm) compared with the preserved latanoprost baseline (all P < 0.01). The triple PF regimen demonstrated similar tear film break-up times (6.1 vs 6.0 s) and Schirmer I test results (8.2 vs 8.2 mm) to latanoprost, but revealed a significant improvement in the corneal stain test (1.7 vs 2.2; P < 0.001). In this trial PF tafluprost therapy provided statistically greater 24-h efficacy and improved tolerability compared with preserved latanoprost. The combination of PF tafluprost and PF dorzolamide/timolol fixed combination was statistically and clinically more efficacious than both monotherapies and demonstrated similar ocular surface characteristics to preserved latanoprost monotherapy. ClinicalTrials.gov (NCT02802137). Santen.

Synthesis, characterisation and antibacterial activity of [(p-cym)RuX(L)](+/2+) (X = Cl, H2O; L = bpmo, bpms) complexes.

PubMed

Tripathy, Suman Kumar; Taviti, Ashoka Chary; Dehury, Niranjan; Sahoo, Anupam; Pal, Satyanaryan; Beuria, Tushar Kant; Patra, Srikanta

2015-03-21

Mononuclear half-sandwiched complexes [(p-cym)RuCl(bpmo)](ClO4) {[1](ClO4)} and [(p-cym)RuCl(bpms)](PF6) {[2](PF6)} have been prepared by reacting heteroscorpionate ligands bpmo = 2-methoxyphenyl-bis(3,5-dimethylpyrazol-1-yl)methane and bpms = 2-methylthiophenyl-bis(3,5-dimethylpyrazol-1-yl)methane, respectively, with a dimeric precursor complex [(p-cym)RuCl(μ-Cl)]2 (p-cym = 1-isopropyl-4-methylbenzene) in methanol. The corresponding aqua derivatives [(p-cym)Ru(H2O)(bpmo)](ClO4)2 {[3](ClO4)2} and [(p-cym)Ru(H2O)(bpms)](PF6)2 {[4](PF6)2} are obtained from {[1](ClO4)} and {[2](PF6)}, respectively, via Cl(-)/H2O exchange process in the presence of appropriate equivalents of AgClO4/AgNO3 + KPF6 in a methanol-water mixture. The molecular structures of the complexes {[1]Cl, [3](ClO4)2 and [4](PF6)(NO3)} are authenticated by their single crystal X-ray structures. The complexes show the expected piano-stool geometry with p-cym in the η(6) binding mode. The aqua complexes [3](ClO4)2 and [4](PF6)2 show significantly good antibacterial activity towards E. coli (gram negative) and B. subtilis (gram positive) strains, while chloro derivatives ({[1](ClO4)} and {[2](PF6)} are found to be virtually inactive. The order of antibacterial activity of the complexes according to their MIC values is [1](ClO4) (both 1000 μg mL(-1)) < [2](PF6) (580 μg mL(-1) and 750 μg mL(-1)) < [3](ClO4)2 (both 100 μg mL(-1)) < [4](PF6)2 (30 μg mL(-1) and 60 μg mL(-1)) for E. coli and B. subtilis strains, respectively. Further, the aqua complexes [3](ClO4)2 and [4](PF6)2 show clear zones of inhibition against kanamycin, ampicillin and chloramphenicol resistant E. coli strains. The detailed mechanistic aspects of the aforesaid active aqua complexes [3](ClO4)2 and [4](PF6)2 have been explored, and it reveals that both the complexes inhibit the number of nucleoids per cell in vivo and bind to DNA in vitro. The results indeed demonstrate that both [3](ClO4)2 and [4](PF6)2 facilitate the inhibition of bacterial growth by binding to DNA.

Using transparent polyurethane film and hydrocolloid dressings to prevent pressure ulcers.

PubMed

Dutra, R A A; Salomé, G M; Alves, J R; Pereira, V O S; Miranda, F D; Vallim, V B; de Brito, M J A; Ferreira, L M

2015-06-01

To compare the performance and effectiveness of a hydrocolloid dressing (HD) and a transparent polyurethane film (PF) in preventing pressure ulcer (PU) development. The study was conducted in the intensive care unit, coronary care unit and medical clinic of the Holy House of Mercy of Passos, Brazil. Data were collected 48 hours after admission and during hospitalisation. The Braden scale was used for PU risk assessment. Consecutive eligible patients without PUs were randomly assigned by lottery to the two groups, either the HD or PF group. Of the 160 eligible patients, significant between-group differences were found in the mean total number of dressing changes (HD, 6.09±1.655 changes; PF, 5.59±2.036 changes; p=0.010), and mean number of dressing changes in the sacral region (HD, 2.50±0.871; PF, 2.05±0.825; p=0.001), with the PF group requiring significantly fewer changes than the HD group. The most common reasons for changing dressings in both groups were moisture (PF 51.1%; HD 47.9%) and shear (HD 43%; PF 38.9%), with a significant difference in shear between groups. The incidence of PUs was significantly lower (p=0.038) in the PF group (8.7%) compared with that in the HD group (15%). The results suggest that the transparent polyurethane film had a better performance and was more effective than the hydrocolloid dressing in preventing PU development.