An insertion in the methyltransferase domain of P. falciparum trimethylguanosine synthase harbors a classical nuclear localization signal.

PubMed

Babar, Prasad H; Dey, Vishakha; Jaiswar, Praveen; Patankar, Swati

Many Plasmodium falciparum proteins do not share homology with, and are generally longer than their respective orthologs. This, to some extent, can be attributed to insertions. Here, we studied a P. falciparum RNA hypermethylase, trimethylguanosine synthase (PfTGS1) that harbors a 76 amino acid insertion in its methyltransferase domain. Bioinformatics analysis revealed that this insertion was present in TGS1 orthologs from other Plasmodium species as well. Interestingly, a classical nuclear localization signal (NLS) was predicted in the insertions of primate parasite TGS1 proteins. To check whether these predicted NLS are functional, we developed an in vivo heterologous system using S. cerevisiae. The predicted NLS when fused to dimeric GFP were able to localize the fusion protein to the nucleus in yeast indicating that it is indeed recognized by the yeast nuclear import machinery. We further showed that the PfTGS1 NLS binds to P. falciparum importin-α in vitro, confirming that the NLS is also recognized by the P. falciparum classical nuclear import machinery. Thus, in this study we report a novel function of the insertion in PfTGS1. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Clinical Application of Insertion Force Sensor System for Coil Embolization of Intracranial Aneurysms.

PubMed

Matsubara, Noriaki; Miyachi, Shigeru; Izumi, Takashi; Yamada, Hiroyuki; Marui, Naoki; Ota, Keisuke; Tajima, Hayato; Shintai, Kazunori; Ito, Masashi; Imai, Tasuku; Nishihori, Masahiro; Wakabayashi, Toshihiko

2017-09-01

In endovascular embolization for intracranial aneurysms, it is important to properly control the coil insertion force. However, the force can only be subjectively detected by the subtle feedback experienced by neurointerventionists at their fingertips. The authors envisioned a system that would objectively sense and quantify that force. In this article, coil insertion force was measured in cases of intracranial aneurysm using this sensor, and its actual clinical application was investigated. The sensor consists of a hemostatic valve (Y-connector). A little flexure was intentionally added in the device, and it creates a bend in the delivery wire. The sensor measures the change in the position of the bent wire depending on the insertion force and translates it into a force value. Using this, embolization was performed for 10 unruptured intracranial aneurysms. The sensor adequately recorded the force, and it reflected the operators' usual clinical experience. The presence of the sensor did not affect the procedures. The sensor enabled the operators to objectively note and evaluate the insertion force and better cooperative handling was possible. Additionally, other members of the intervention team shared the information. Force records demonstrated the characteristic patterns according to every stage of coiling (framing, filling, and finishing). The force sensor system adequately measured coil insertion force in intracranial aneurysm coil embolization procedures. The safety of this sensor was demonstrated in clinical application for the limited number of patients. This system is useful adjunct for assisting during coil embolization for an intracranial aneurysm. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Generation of 24 T at 4.2 K using a layer-wound GdBCO insert coil with Nb3Sn and Nb-Ti external magnetic field coils

NASA Astrophysics Data System (ADS)

Matsumoto, S.; Kiyoshi, T.; Otsuka, A.; Hamada, M.; Maeda, H.; Yanagisawa, Y.; Nakagome, H.; Suematsu, H.

2012-02-01

High-temperature superconducting (HTS) magnets are believed to be a practical option in the development of high field nuclear magnetic resonance (NMR) systems. The development of a 600 MHz NMR system that uses an HTS magnet and a probe with an HTS radio frequency coil is underway. The HTS NMR magnet is expected to reduce the volume occupied by the magnet and to encourage users to install higher field NMR systems. The tolerance to high tensile stress is expected for HTS conductors in order to reduce the magnet in volume. A layer-wound Gd-Ba-Cu-O (GdBCO) insert coil was fabricated in order to investigate its properties under a high electromagnetic force in a high magnetic field. The GdBCO insert coil was successfully operated at a current of up to 321 A and an electromagnetic force BJR of 408 MPa in an external magnetic field generated by Nb3Sn and Nb-Ti low-temperature superconducting coils. The GdBCO insert coil also managed to generate a magnetic field of 6.8 T at the center of the coil in an external magnetic field of 17.2 T. The superconducting magnet consisting of GdBCO, Nb3Sn and Nb-Ti coils successfully generated a magnetic field of 24.0 T at 4.2 K, which represents a new record for a superconducting magnet.

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.

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.

All-atom simulations and free-energy calculations of coiled-coil peptides with lipid bilayers: binding strength, structural transition, and effect on lipid dynamics

NASA Astrophysics Data System (ADS)

Woo, Sun Young; Lee, Hwankyu

2016-03-01

Peptides E and K, which are synthetic coiled-coil peptides for membrane fusion, were simulated with lipid bilayers composed of lipids and cholesterols at different ratios using all-atom models. We first calculated free energies of binding from umbrella sampling simulations, showing that both E and K peptides tend to adsorb onto the bilayer surface, which occurs more strongly in the bilayer composed of smaller lipid headgroups. Then, unrestrained simulations show that K peptides more deeply insert into the bilayer with partially retaining the helical structure, while E peptides less insert and predominantly become random coils, indicating the structural transition from helices to random coils, in quantitative agreement with experiments. This is because K peptides electrostatically interact with lipid phosphates, as well as because hydrocarbons of lysines of K peptide are longer than those of glutamic acids of E peptide and thus form stronger hydrophobic interactions with lipid tails. This deeper insertion of K peptide increases the bilayer dynamics and a vacancy below the peptide, leading to the rearrangement of smaller lipids. These findings help explain the experimentally observed or proposed differences in the insertion depth, binding strength, and structural transition of E and K peptides, and support the snorkeling effect.

All-atom simulations and free-energy calculations of coiled-coil peptides with lipid bilayers: binding strength, structural transition, and effect on lipid dynamics.

PubMed

Woo, Sun Young; Lee, Hwankyu

2016-03-01

Peptides E and K, which are synthetic coiled-coil peptides for membrane fusion, were simulated with lipid bilayers composed of lipids and cholesterols at different ratios using all-atom models. We first calculated free energies of binding from umbrella sampling simulations, showing that both E and K peptides tend to adsorb onto the bilayer surface, which occurs more strongly in the bilayer composed of smaller lipid headgroups. Then, unrestrained simulations show that K peptides more deeply insert into the bilayer with partially retaining the helical structure, while E peptides less insert and predominantly become random coils, indicating the structural transition from helices to random coils, in quantitative agreement with experiments. This is because K peptides electrostatically interact with lipid phosphates, as well as because hydrocarbons of lysines of K peptide are longer than those of glutamic acids of E peptide and thus form stronger hydrophobic interactions with lipid tails. This deeper insertion of K peptide increases the bilayer dynamics and a vacancy below the peptide, leading to the rearrangement of smaller lipids. These findings help explain the experimentally observed or proposed differences in the insertion depth, binding strength, and structural transition of E and K peptides, and support the snorkeling effect.

α/β coiled coils

PubMed Central

Hartmann, Marcus D; Mendler, Claudia T; Bassler, Jens; Karamichali, Ioanna; Ridderbusch, Oswin; Lupas, Andrei N; Hernandez Alvarez, Birte

2016-01-01

Coiled coils are the best-understood protein fold, as their backbone structure can uniquely be described by parametric equations. This level of understanding has allowed their manipulation in unprecedented detail. They do not seem a likely source of surprises, yet we describe here the unexpected formation of a new type of fiber by the simple insertion of two or six residues into the underlying heptad repeat of a parallel, trimeric coiled coil. These insertions strain the supercoil to the breaking point, causing the local formation of short β-strands, which move the path of the chain by 120° around the trimer axis. The result is an α/β coiled coil, which retains only one backbone hydrogen bond per repeat unit from the parent coiled coil. Our results show that a substantially novel backbone structure is possible within the allowed regions of the Ramachandran space with only minor mutations to a known fold. DOI: http://dx.doi.org/10.7554/eLife.11861.001 PMID:26771248

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.

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.

MR-compatibility assessment of MADPET4: a study of interferences between an SiPM-based PET insert and a 7 T MRI system.

PubMed

Omidvari, Negar; Topping, Geoffrey; Cabello, Jorge; Paul, Stephan; Schwaiger, Markus; Ziegler, Sibylle I

2018-05-01

Compromises in the design of a positron emission tomography (PET) insert for a magnetic resonance imaging (MRI) system should minimize the deterioration of image quality in both modalities, particularly when simultaneous demanding acquisitions are performed. In this work, the advantages of using individually read-out crystals with high-gain silicon photomultipliers (SiPMs) were studied with a small animal PET insert for a 7 T MRI system, in which the SiPM charge was transferred to outside the MRI scanner using coaxial cables. The interferences between the two systems were studied with three radio-frequency (RF) coil configurations. The effects of PET on the static magnetic field, flip angle distribution, RF noise, and image quality of various MRI sequences (gradient echo, spin echo, and echo planar imaging (EPI) at 1 H frequency, and chemical shift imaging at 13 C frequency) were investigated. The effects of fast-switching gradient fields and RF pulses on PET count rate were studied, while the PET insert and the readout electronics were not shielded. Operating the insert inside a 1 H volume coil, used for RF transmission and reception, limited the MRI to T1-weighted imaging, due to coil detuning and RF attenuation, and resulted in significant PET count loss. Using a surface receive coil allowed all tested MR sequences to be used with the insert, with 45-59% signal-to-noise ratio (SNR) degradation, compared to without PET. With a 1 H/ 13 C volume coil inside the insert and shielded by a copper tube, the SNR degradation was limited to 23-30% with all tested sequences. The insert did not introduce any discernible distortions into images of two tested EPI sequences. Use of truncated sinc shaped RF excitation pulses and gradient field switching had negligible effects on PET count rate. However, PET count rate was substantially affected by high-power RF block pulses and temperature variations due to high gradient duty cycles.

Recent Progress of the Series-Connected Hybrid Magnet Projects

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

Adkins, Todd; Bole, Scott

2010-01-01

The National High Magnetic Field Laboratory (NHMFL) in Tallahassee, Florida has designed and is now constructing two Series Connected Hybrid (SCH) magnets, each connecting a superconducting outsert coil and a resistive Florida Bitter insert coil electrically in series. The SCH to be installed at the NHMFL will produce 36 T and provide 1 ppm maximum field inhomogeneity over a 1 cm diameter spherical volume. The SCH to be installed at the Helmholtz Center Berlin (HZB) in combination with a neutron source will produce 25 T to 30 T depending on the resistive insert. The two magnets have a common designmore » for their cable-in-conduit conductor (CICC) and superconducting outsert coils. The CICC outsert coil winding packs have an inner diameter of 0.6 m and contribute 13.1 T to the central field using three grades of CICC conductors. Each conductor grade carries 20 kA and employs the same type of Nb{sub 3}Sn superconducting wire, but each grade contains different quantities of superconducting wires, different cabling patterns and different aspect ratios. The cryostats and resistive insert coils for the two magnets are different. This paper discusses the progress in CIC conductor and coil fabrication over the last year including specification, qualification and production activities for wire, cable, conductor and coil processing.« less

Coil spring venting arrangement

DOEpatents

McCugh, R.M.

1975-10-21

A simple venting device for trapped gas pockets in hydraulic systems is inserted through a small access passages, operated remotely, and removed completely. The device comprises a small diameter, closely wound coil spring which is pushed through a guide temporarily inserted in the access passage. The guide has a central passageway which directs the coil spring radially upward into the pocket, so that, with the guide properly positioned for depth and properly oriented, the coil spring can be pushed up into the top of the pocket to vent it. By positioning a seal around the free end of the guide, the spring and guide are removed and the passage is sealed.

Construction and Test Results of Coil 2 of a Three-Coil 800-MHz REBCO Insert for the 1.3-GHz High-Resolution NMR Magnet.

PubMed

Bascuñán, Juan; Michael, Philip; Hahn, Seungyong; Lecrevisse, Thibault; Iwasa, Yukikazu

2017-06-01

This paper focuses on the construction and test results of Coil 2 that is part of a trio of nested coils composing the REBCO 800 MHz insert. Upon its completion, the REBCO 800 MHz insert will be placed in the bore of a 500 MHz low temperature superconducting (LTS) NMR magnet (L500) to form the MIT 1.3 GHz high-resolution NMR magnet. Coil 2 is a stack of 32 double pancake (DP) coils wound with 6-mm wide REBCO tape using the no-insulation (NI) technique. Each pancake is wound on a stainless steel inner supporting ring to prevent the collapsing of its crossover due to the external pressure exerted by the winding pack. Coil 2 will be constructed in the following sequence: 1) after winding each DP will be individually tested in a bath of liquid nitrogen at atmospheric pressure to determine its current carrying capabilities; 2) DPs will be then assembled as a stack with interconnecting joints, and 3) as in Coil 1, each pancake will be overbanded with a stainless steel tape, this time to a thickness of 5 mm, thickness determined by a stress analysis previously performed. Finally the fully assembled Coil 2 will be tested in liquid nitrogen at 77 K and then in liquid helium at 4.2 K. We present here details of the stress analysis leading to the sizing of the DP inner supporting stainless steel ring and of the overbanding thickness required. Test results include coil index, critical current, charging time constant.

Shielded resistive electromagnets of arbitrary surface geometry using the boundary element method and a minimum energy constraint.

PubMed

Harris, Chad T; Haw, Dustin W; Handler, William B; Chronik, Blaine A

2013-09-01

Eddy currents are generated in MR by the use of rapidly switched electromagnets, resulting in time varying and spatially varying magnetic fields that must be either minimized or corrected. This problem is further complicated when non-cylindrical insert magnets are used for specialized applications. Interruption of the coupling between an insert coil and the MR system is typically accomplished using active magnetic shielding. A new method of actively shielding insert gradient and shim coils of any surface geometry by use of the boundary element method for coil design with a minimum energy constraint is presented. This method was applied to shield x- and z-gradient coils for two separate cases: a traditional cylindrical primary gradient with cylindrical shield and, to demonstrate its versatility in surface geometry, the same cylindrical primary gradients with a rectangular box-shaped shield. For the cylindrical case this method produced shields that agreed with analytic solutions. For the second case, the rectangular box-shaped shields demonstrated very good shielding characteristics despite having a different geometry than the primary coils. Copyright © 2013 Elsevier Inc. 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.

MR Performance Comparison of a PET/MR System Before and After SiPM-Based Time-of-Flight PET Detector Insertion

NASA Astrophysics Data System (ADS)

Khalighi, Mohammad Mehdi; Delso, Gaspar; Maramraju, Sri Harsha; Deller, Timothy W.; Levin, Craig S.; Glover, Gary H.

2016-10-01

A silicon photomultiplier (SiPM)-based time-of-flight capable PET detector has been integrated with a 70 cm wide-bore 3T MR scanner for simultaneous whole-body imaging (MR750w, GE Healthcare, Waukesha, WI). After insertion of the PET detector, the final PET/MR bore is 60 cm wide (SIGNA PET/MR, GE Healthcare, Waukesha, WI). The MR performance was compared before and after the PET ring insertion. B0 homogeneity, B1+ uniformity of the body coil along with peak B1+, coherent noise, and FBIRN (Function Biomedical Informatics Research Network) tests are used to compare the MR performance. It is shown that B0 homogeneity and coherent noise have not changed according to the system specifications. Peak B1+ is increased by 33% and B1+ inhomogeneity is increased by 4% after PET ring insertion due to a smaller diameter body coil design. The FBIRN test shows similar temporal stability before and after PET ring insertion. Due to a smaller body coil on the PET/MR system, the signal fluctuation to noise ratio (SFNR) and SNR for body receive coil, are improved by 40% and 160% for Echo Planar Imaging (EPI) and spiral sequences respectively. Comparison using RF- and gradient-intensive clinical sequences shows inserting the PET detectors into the wide-bore MRI has not compromised the MR image quality according to these tests.

MR-compatibility assessment of MADPET4: a study of interferences between an SiPM-based PET insert and a 7 T MRI system

NASA Astrophysics Data System (ADS)

Omidvari, Negar; Topping, Geoffrey; Cabello, Jorge; Paul, Stephan; Schwaiger, Markus; Ziegler, Sibylle I.

2018-05-01

Compromises in the design of a positron emission tomography (PET) insert for a magnetic resonance imaging (MRI) system should minimize the deterioration of image quality in both modalities, particularly when simultaneous demanding acquisitions are performed. In this work, the advantages of using individually read-out crystals with high-gain silicon photomultipliers (SiPMs) were studied with a small animal PET insert for a 7 T MRI system, in which the SiPM charge was transferred to outside the MRI scanner using coaxial cables. The interferences between the two systems were studied with three radio-frequency (RF) coil configurations. The effects of PET on the static magnetic field, flip angle distribution, RF noise, and image quality of various MRI sequences (gradient echo, spin echo, and echo planar imaging (EPI) at 1H frequency, and chemical shift imaging at 13C frequency) were investigated. The effects of fast-switching gradient fields and RF pulses on PET count rate were studied, while the PET insert and the readout electronics were not shielded. Operating the insert inside a 1H volume coil, used for RF transmission and reception, limited the MRI to T1-weighted imaging, due to coil detuning and RF attenuation, and resulted in significant PET count loss. Using a surface receive coil allowed all tested MR sequences to be used with the insert, with 45–59% signal-to-noise ratio (SNR) degradation, compared to without PET. With a 1H/13C volume coil inside the insert and shielded by a copper tube, the SNR degradation was limited to 23–30% with all tested sequences. The insert did not introduce any discernible distortions into images of two tested EPI sequences. Use of truncated sinc shaped RF excitation pulses and gradient field switching had negligible effects on PET count rate. However, PET count rate was substantially affected by high-power RF block pulses and temperature variations due to high gradient duty cycles.

A proposed model membrane and test method for microneedle insertion studies.

PubMed

Larrañeta, Eneko; Moore, Jessica; Vicente-Pérez, Eva M; González-Vázquez, Patricia; Lutton, Rebecca; Woolfson, A David; Donnelly, Ryan F

2014-09-10

A commercial polymeric film (Parafilm M(®), a blend of a hydrocarbon wax and a polyolefin) was evaluated as a model membrane for microneedle (MN) insertion studies. Polymeric MN arrays were inserted into Parafilm M(®) (PF) and also into excised neonatal porcine skin. Parafilm M(®) was folded before the insertions to closely approximate thickness of the excised skin. Insertion depths were evaluated using optical coherence tomography (OCT) using either a force applied by a Texture Analyser or by a group of human volunteers. The obtained insertion depths were, in general, slightly lower, especially for higher forces, for PF than for skin. However, this difference was not a large, being less than the 10% of the needle length. Therefore, all these data indicate that this model membrane could be a good alternative to biological tissue for MN insertion studies. As an alternative method to OCT, light microscopy was used to evaluate the insertion depths of MN in the model membrane. This provided a rapid, simple method to compare different MN formulations. The use of Parafilm M(®), in conjunction with a standardised force/time profile applied by a Texture Analyser, could provide the basis for a rapid MN quality control test suitable for in-process use. It could also be used as a comparative test of insertion efficiency between candidate MN formulations. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Purposeful creation of a pneumothorax and chest tube placement to facilitate CT-guided coil localization of lung nodules before video-assisted thoracoscopic surgical wedge resection.

PubMed

Iqbal, Shams I; Molgaard, Christopher; Williamson, Christina; Flacke, Sebastian

2014-07-01

To evaluate the feasibility and efficacy of pneumothorax creation and chest tube insertion before computed tomography (CT)-guided coil localization of small peripheral lung nodules for video-assisted thoracoscopic surgical (VATS) wedge resection. From May 2011 to October 2013, 21 consecutive patients (seven men; mean age, 62 y; range, 42-76 y) scheduled for VATS wedge resection required CT-guided coil localization for small, likely nonpalpable peripheral lung lesions at a single institution. Outcomes were evaluated retrospectively for technical success and complications. There were 12 nodules and nine ground-glass opacities. Mean lesion distance from the pleural surface was 15 mm (range, 5-35 mm), and average size was 13 mm (range, 7-30 mm). A pneumothorax was successfully created in all patients with a Veress needle, and a chest tube was inserted. All target lesions were marked successfully, leaving one end of the coil within/beyond the lesion and the other end of the coil in the pleural space. The inserted chest tube was used to insufflate air to widen the pleural space during coil positioning and to aspirate any residual air before transfer of the patient to the operating room holding area. Intraparenchymal hemorrhages smaller than 7 cm in diameter developed in two patients during coil placement. All lesions were successfully resected with VATS. Histologic examinaiton revealed 13 primary adenocarcinomas, four metastases, and four benign lesions. Pneumothorax creation and chest tube placement before CT-guided coil localization of peripheral lung nodules for VATS wedge resection facilitates the deployment of the peripheral end of the coil in the pleural space and provides effective management of procedure-related pneumothorax until surgery. Copyright © 2014 SIR. Published by Elsevier Inc. All rights reserved.

Functional Investigation of the Plant-Specific Long Coiled-Coil Proteins PAMP-INDUCED COILED-COIL (PICC) and PICC-LIKE (PICL) in Arabidopsis thaliana

PubMed Central

Venkatakrishnan, Sowmya; Mackey, David; Meier, Iris

2013-01-01

We have identified and characterized two Arabidopsis long coiled-coil proteins PAMP-INDUCED COILED-COIL (PICC) and PICC-LIKE (PICL). PICC (147 kDa) and PICL (87 kDa) are paralogs that consist predominantly of a long coiled-coil domain (expanded in PICC), with a predicted transmembrane domain at the immediate C-terminus. Orthologs of PICC and PICL were found exclusively in vascular plants. PICC and PICL GFP fusion proteins are anchored to the cytoplasmic surface of the endoplasmic reticulum (ER) membrane by a C-terminal transmembrane domain and a short tail domain, via a tail-anchoring mechanism. T-DNA-insertion mutants of PICC and PICL as well as the double mutant show an increased sensitivity to the plant abiotic stress hormone abscisic acid (ABA) in a post-germination growth response. PICC, but not PICL gene expression is induced by the bacterial pathogen-associated molecular pattern (PAMP) flg22. T-DNA insertion alleles of PICC, but not PICL, show increased susceptibility to the non-virulent strain P. syringae pv. tomato DC3000 hrcC, but not to the virulent strain P. syringae pv. tomato DC3000. This suggests that PICC mutants are compromised in PAMP-triggered immunity (PTI). The data presented here provide first evidence for the involvement of a plant long coiled-coil protein in a plant defense response. PMID:23451199

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.

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

DOE PAGES

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

2016-03-02

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

The accommodation index measures the perturbation associated with insertions and deletions in coiled‐coils: Application to understand signaling in histidine kinases

PubMed Central

Schmidt, Nathan W.; Grigoryan, Gevorg

2017-01-01

Abstract Coiled‐coils are essential components of many protein complexes. First discovered in structural proteins such as keratins, they have since been found to figure largely in the assembly and dynamics required for diverse functions, including membrane fusion, signal transduction and motors. Coiled‐coils have a characteristic repeating seven‐residue geometric and sequence motif, which is sometimes interrupted by the insertion of one or more residues. Such insertions are often highly conserved and critical to interdomain communication in signaling proteins such as bacterial histidine kinases. Here we develop the “accommodation index” as a parameter that allows automatic detection and classification of insertions based on the three dimensional structure of a protein. This method allows precise identification of the type of insertion and the “accommodation length” over which the insertion is structurally accommodated. A simple theory is presented that predicts the structural perturbations of 1, 3, 4 residue insertions as a function of the length over which the insertion is accommodated. Analysis of experimental structures is in good agreement with theory, and shows that short accommodation lengths give rise to greater perturbation of helix packing angles, changes in local helical phase, and increased structural asymmetry relative to long accommodation lengths. Cytoplasmic domains of histidine kinases in different signaling states display large changes in their accommodation lengths, which can now be seen to underlie diverse structural transitions including symmetry/asymmetry and local variations in helical phase that accompany signal transduction. PMID:27977891

Construction and Test Results of Coils 2 and 3 of a 3-Nested-Coil 800-MHz REBCO Insert for the MIT 1.3-GHz LTS/HTS NMR Magnet.

PubMed

Park, Dongkeun; Bascuñán, Juan; Michael, Philip C; Lee, Jiho; Hahn, Seungyong; Iwasa, Yukikazu

2018-04-01

We present construction and test results of Coils 2 and 3 of a 3-coil 800-MHz REBCO insert (H800) for the MIT 1.3 GHz LTS/HTS NMR magnet currently under construction. Each of three H800 coils (Coils 1-3) is a stack of no-insulation REBCO double pancakes (DPs). The innermost 8.67-T Coil 1 (26 DPs) was completed in 2016; the middle 5.64-T Coil 2 (32 DPs) has been wound, assembled, and tested; and for the outermost 4.44-T Coil 3, its 38 DPs have been wound and preliminary tests were performed to characterize each DP at 77 K. Included for Coil 2 are: 1) 77-K data of critical current, index, and turn-to-turn characteristic resistivity of each DP; 2) stacking order of the 32 DPs optimized to maximize the Coil 2 current margin and minimize its Joule dissipation in the pancake-to-pancake joints; 3) procedure to experimentally determine and apply a room-temperature preload to the DP stack; 4) 77-K and 4.2-K test results after each of 64 pancakes was over-banded with 75-μm-thick stainless steel tape for a radial thickness of 5 mm. Presented for each DP in Coil 3 are 77-K dada of critical current, index, and turn-to-turn characteristic resistivity.

Metal-as-insulation variant of no-insulation HTS winding technique: pancake tests under high background magnetic field and high current at 4.2 K

NASA Astrophysics Data System (ADS)

Lécrevisse, T.; Badel, A.; Benkel, T.; Chaud, X.; Fazilleau, P.; Tixador, P.

2018-05-01

In the framework of a project aiming at fabricating a 10 T high temperature superconducting (HTS) insert to operate in a 20 T background field, we are investigating the behavior of pancakes consisting of a REBCO HTS tape co-wound with a stainless steel tape (metal-as-insulation (MI) coil). The MI winding is inducing a significant turn-to-turn electrical resistance which helps to reduce the charging time delay. Despite this resistance, the self-protection feature of no-insulation coils is still enabled, thanks to the voltage limit of the power supply. We have built a single pancake coil representative of the pancake that will be used in the insert and performed tests under very high background magnetic field. Our coil experienced over 100 heater induced quenches without a measureable increase of its internal resistance. We have gathered stability and quench behavior data for magnetic fields and engineering current densities (je ) in the range of 0–17 T and 0–635 A mm‑2 respectively. We also present our very first experiments on the insert/outsert interaction in the case of a resistive magnet fault. We show that if self-protection of the MI winding is really effective in the case of a MI coil quench, a major issue comes from the outsert fault which induces a huge current inside the MI coil.

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.

Primary Care Management of Plantar Fasciitis.

PubMed

Melvin, Thomas J; Tankersley, Zach J; Qazi, Zain N; Jasko, John J; Odono, Russell; Shuler, Franklin D

2015-01-01

Plantar fasciitis (PF) is present in 10% of the population and is the most common cause of plantar heel pain. PF is painful, can alter daily activities and presents as a sharp pain localized to the plantar foot and medial heel. The underlying etiology involves microtrauma to the plantar fascia, specifically at its insertion point on the calcaneus. Successful management of plantar fasciitis is typically achieved with the conservative therapy approaches discussed.

Actinomyces bacteremia in association with tubo-ovarian abscesses and hysteroscopic sterilization.

PubMed

Pakish, Janelle B; West, Loyd

2014-08-01

Actinomyces infection is well-documented in intrauterine devices but has not been previously associated with hysteroscopic sterilization using coil inserts. Additionally, abscesses associated with these implants have been observed in few cases. A 31-year-old multiparous woman with a history of hysteroscopic sterilization with coil inserts 18 months previously presented with several weeks of pelvic pain. Despite percutaneous drainage of intra-abdominal abscesses, her pain and fevers persisted. Blood cultures were positive for Actinomyces infection, and exploratory laparotomy demonstrated abscesses at both coil sites. When a causative organism cannot be identified or the when patient does not respond to standard antibiotic therapy, Actinomyces infection should be considered because prolonged antibiotic therapy is necessary.

A Modified Alderman-Grant Coil makes possible an efficient cross-coil probe for high field solid-state NMR of lossy biological samples

NASA Astrophysics Data System (ADS)

Grant, Christopher V.; Yang, Yuan; Glibowicka, Mira; Wu, Chin H.; Park, Sang Ho; Deber, Charles M.; Opella, Stanley J.

2009-11-01

The design, construction, and performance of a cross-coil double-resonance probe for solid-state NMR experiments on lossy biological samples at high magnetic fields are described. The outer coil is a Modified Alderman-Grant Coil (MAGC) tuned to the 1H frequency. The inner coil consists of a multi-turn solenoid coil that produces a B 1 field orthogonal to that of the outer coil. This results in a compact nested cross-coil pair with the inner solenoid coil tuned to the low frequency detection channel. This design has several advantages over multiple-tuned solenoid coil probes, since RF heating from the 1H channel is substantially reduced, it can be tuned for samples with a wide range of dielectric constants, and the simplified circuit design and high inductance inner coil provides excellent sensitivity. The utility of this probe is demonstrated on two electrically lossy samples of membrane proteins in phospholipid bilayers (bicelles) that are particularly difficult for conventional NMR probes. The 72-residue polypeptide embedding the transmembrane helices 3 and 4 of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) (residues 194-241) requires a high salt concentration in order to be successfully reconstituted in phospholipid bicelles. A second application is to paramagnetic relaxation enhancement applied to the membrane-bound form of Pf1 coat protein in phospholipid bicelles where the resistance to sample heating enables high duty cycle solid-state NMR experiments to be performed.

Prediction, experimental results and analysis of the ITER TF insert coil quench propagation tests, using the 4C code

NASA Astrophysics Data System (ADS)

Zanino, R.; Bonifetto, R.; Brighenti, A.; Isono, T.; Ozeki, H.; Savoldi, L.

2018-07-01

The ITER toroidal field insert (TFI) coil is a single-layer Nb3Sn solenoid tested in 2016-2017 at the National Institutes for Quantum and Radiological Science and Technology (former JAEA) in Naka, Japan. The TFI, the last in a series of ITER insert coils, was tested in operating conditions relevant for the actual ITER TF coils, inserting it in the borehole of the central solenoid model coil, which provided the background magnetic field. In this paper, we consider the five quench propagation tests that were performed using one or two inductive heaters (IHs) as drivers; out of these, three used just one IH but with increasing delay times, up to 7.5 s, between the quench detection and the TFI current dump. The results of the 4C code prediction of the quench propagation up to the current dump are presented first, based on simulations performed before the tests. We then describe the experimental results, showing good reproducibility. Finally, we compare the 4C code predictions with the measurements, confirming the 4C code capability to accurately predict the quench propagation, and the evolution of total and local voltages, as well as of the hot spot temperature. To the best of our knowledge, such a predictive validation exercise is performed here for the first time for the quench of a Nb3Sn coil. Discrepancies between prediction and measurement are found in the evolution of the jacket temperatures, in the He pressurization and quench acceleration in the late phase of the transient before the dump, as well as in the early evolution of the inlet and outlet He mass flow rate. Based on the lessons learned in the predictive exercise, the model is then refined to try and improve a posteriori (i.e. in interpretive, as opposed to predictive mode) the agreement between simulation and experiment.

High frequency magnetostrictive transducers for waveguide applications

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

Daw, Joshua Earl; Taylor, Steven Cheney; Rempe, Joy Lynn

A high frequency magnetostrictive transducer includes a magnetostrictive rod or wire inserted co-axially into a driving coil, wherein the driving coil includes a coil arrangement with a plurality of small coil segments along the magnetostrictive rod or wire; wherein frequency operation of the high frequency magnetostrictive transducer is controlled by a length of the small coil segments and a material type of the magnetostrictive rod or wire. This design of the high frequency magnetostrictive transducer retains the beneficial aspects of the magnetostrictive design, while reducing its primary drawback, lower frequency operation.

Coiled-coil length: Size does matter.

PubMed

Surkont, Jaroslaw; Diekmann, Yoan; Ryder, Pearl V; Pereira-Leal, Jose B

2015-12-01

Protein evolution is governed by processes that alter primary sequence but also the length of proteins. Protein length may change in different ways, but insertions, deletions and duplications are the most common. An optimal protein size is a trade-off between sequence extension, which may change protein stability or lead to acquisition of a new function, and shrinkage that decreases metabolic cost of protein synthesis. Despite the general tendency for length conservation across orthologous proteins, the propensity to accept insertions and deletions is heterogeneous along the sequence. For example, protein regions rich in repetitive peptide motifs are well known to extensively vary their length across species. Here, we analyze length conservation of coiled-coils, domains formed by an ubiquitous, repetitive peptide motif present in all domains of life, that frequently plays a structural role in the cell. We observed that, despite the repetitive nature, the length of coiled-coil domains is generally highly conserved throughout the tree of life, even when the remaining parts of the protein change, including globular domains. Length conservation is independent of primary amino acid sequence variation, and represents a conservation of domain physical size. This suggests that the conservation of domain size is due to functional constraints. © 2015 Wiley Periodicals, Inc.

High performance twisted and coiled soft actuator with spandex fiber for artificial muscles

NASA Astrophysics Data System (ADS)

Yang, Sang Yul; Cho, Kyeong Ho; Kim, Youngeun; Song, Min-Geun; Jung, Ho Sang; Yoo, Ji Wang; Moon, Hyungpil; Koo, Ja Choon; Nam, Jae-do; Ryeol Choi, Hyouk

2017-10-01

This paper reports the twisted and coiled soft actuator (abbreviated with STCA) with spandex fiber. The STCA exhibits higher actuation strain at lower temperature than the previous nylon twisted and coiled soft actuators (abbreviated with NTCAs). While NTCAs are fabricated using a twist-insertion process until coils are formed, a new method is developed to fabricate the STCA using the ultra-stretch of spandex, whereby the STCA is twisted again after the coil has been formed. A 6-gear-twist-insertion device that increases the stability and the fabrication speed is developed to fabricate the STCA. The superior performance exhibited by the STCA is due to the 14% contraction strain of the bare spandex (bare nylon: 4%) and the low spring constant of 0.0115 N mm-1. The maximum tensile actuation strain of STCA was 45% at 130 °C, and the maximum specific work was 1.523 kJ kg-1 at 130 °C. STCA could repeatedly actuate 100 times with a strain change of less than 0.4%.

Simulated Design Strategies for SPECT Collimators to Reduce the Eddy Currents Induced by MRI Gradient Fields

NASA Astrophysics Data System (ADS)

Samoudi, Amine M.; Van Audenhaege, Karen; Vermeeren, Günter; Verhoyen, Gregory; Martens, Luc; Van Holen, Roel; Joseph, Wout

2015-10-01

Combining single photon emission computed tomography (SPECT) with magnetic resonance imaging (MRI) requires the insertion of highly conductive SPECT collimators inside the MRI scanner, resulting in an induced eddy current disturbing the combined system. We reduced the eddy currents due to the insert of a novel tungsten collimator inside transverse and longitudinal gradient coils. The collimator was produced with metal additive manufacturing, that is part of a microSPECT insert for a preclinical SPECT/MRI scanner. We characterized the induced magnetic field due to the gradient field and adapted the collimators to reduce the induced eddy currents. We modeled the x-, y-, and z-gradient coil and the different collimator designs and simulated them with FEKO, a three-dimensional method of moments / finite element methods (MoM/FEM) full-wave simulation tool. We used a time analysis approach to generate the pulsed magnetic field gradient. Simulation results show that the maximum induced field can be reduced by 50.82% in the final design bringing the maximum induced magnetic field to less than 2% of the applied gradient for all the gradient coils. The numerical model was validated with measurements and was proposed as a tool for studying the effect of a SPECT collimator within the MRI gradient coils.

Spatial and Temporal Variations of a Screening Current Induced Magnetic Field in a Double-Pancake HTS Insert of an LTS/HTS NMR Magnet

PubMed Central

Ahn, Min Cheol; Yagai, Tsuyoshi; Hahn, Seungyong; Ando, Ryuya; Bascuñán, Juan; Iwasa, Yukikazu

2010-01-01

This paper presents experimental and simulation results of a screening current induced magnetic field (SCF) in a high temperature superconductor (HTS) insert that constitutes a low-/high-temperature superconductor (LTS/HTS) NMR magnet. In this experiment, the HTS insert, a stack of 50 double-pancake coils, each wound with Bi2223 tape, was operated at 77 K. A screening current was induced in the HTS insert by three magnetic field sources: 1) a self field from the HTS insert; 2) an external field from a 5-T background magnet; and 3) combinations of 1) and 2). For each field excitation, which induced an SCF, its axial field distribution and temporal variations were measured and compared with simulation results based on the critical state model. Agreement on field profile between experiment and simulation is satisfactory but more work is needed to make the simulation useful for designing shim coils that will cancel the SCF. PMID:20401187

Magnetic antenna using metallic glass

NASA Technical Reports Server (NTRS)

Desch, Michael D. (Inventor); Farrell, William M. (Inventor); Houser, Jeffrey G. (Inventor)

1996-01-01

A lightweight search-coil antenna or sensor assembly for detecting magnetic fields and including a multi-turn electromagnetic induction coil wound on a spool type coil form through which is inserted an elongated coil loading member comprised of metallic glass material wrapped around a dielectric rod. The dielectric rod consists of a plastic or a wooden dowel having a length which is relatively larger than its thickness so as to provide a large length-to-diameter ratio. A tri-axial configuration includes a housing in which is located three substantially identical mutually orthogonal electromagnetic induction coil assemblies of the type described above wherein each of the assemblies include an electromagnetic coil wound on a dielectric spool with an elongated metallic glass coil loading member projecting therethrough.

Performance investigation and comparison of different turbulator shapes in solar water heating collector system

NASA Astrophysics Data System (ADS)

Khargotra, Rohit; Dhingra, Sunil; Chauhan, Ranchan; Singh, Tej

2018-05-01

The effective use of solar energy is hindered by the intermittent nature of its availability, limiting its use and effectiveness in domestic and industrial applications especially in water heating. In the present paper, the performance of different turbulator shapes in solar water heating collector system has been studied experimentally and comparison on the output performance has been carried out. Effects of insertion of coil-spring turbulator on heat transfer rate, mass flow rate, heat gain by the fluid etc. is studied by disturbing the flow inside the absorber tubes in a solar flat plate collector. The coil-spring used as a turbulator is placed inside the absorber tube which creates a continuous swirling flow along the tube wall. The results of the heat transfer have been compared well with the available results. The heat transfer rate in the collector has been found to be increased by 18% to 70%. Solar water heater having inserts in the flow tubes perform better than the conventional plain ones. It has been observed that heat losses are reduced consequently increasing the thermal performance to about 70% over the plain water heater under same operating conditions. The coil-spring used as a turbulator is placed inside the riser tube while the twisted tape is inserted into the wire coil to create a continuous swirling flow along the tube wall. The results of the heat transfer have been compared with the available results. Solar water heater having inserts in the flow tubes perform better than the conventional plain ones.

Passive energy dump for superconducting coil protection

DOEpatents

Luton, J.N. Jr.

1973-01-16

The patent describes a passive resistance type energy dump for the protection of the coils of a superconducting magnet. Insertion heaters are immersed in a rigid container filled with a fusible alloy. The energy dump is connected across the coils of the superconducting magnet wherein individual heater elements are connected singly to the windings or otherwise according to the energy dumping requirements upon transition of the magnet to a normal state.

Assessment of conductor degradation in the ITER CS insert coil and implications for the ITER conductors

NASA Astrophysics Data System (ADS)

Mitchell, N.

2007-01-01

Nb3Sn cable in conduit-type conductors were expected to provide an efficient way of achieving large conductor currents at high field (up to 13 T) combined with good stability to electromagnetic disturbances due to the extensive helium contact area with the strands. Although ITER model coils successfully reached their design performance (Kato et al 2001 Fusion Eng. Des. 56/57 59-70), initial indications (Mitchell 2003 Fusion Eng. Des. 66-68 971-94) that there were unexplained performance shortfalls have been confirmed. Recent conductor tests (Pasztor et al 2004 IEEE Trans. Appl. Supercond. 14 1527-30) and modelling work (Mitchell 2005 Supercond. Sci. Technol. 18 396-404) suggest that the shortfalls are due to a combination of strand bending and filament fracture under the transverse magnetic loads. Using the new model, the extensive database from the ITER CS insert coil has been reassessed. A parametric fit based on a loss of filament area and n (the exponent of the power-law fit to the electric field) combined with a more rigorous consideration of the conductor field gradient has enabled the coil behaviour to be explained much more consistently than in earlier assessments, now fitting the Nb3Sn strain scaling laws when used with measurements of the conductor operating strain, including conditions when the insert coil current (and hence operating strain) were reversed. The coil superconducting performance also shows a fatigue-type behaviour consistent with recent measurements on conductor samples (Martovetsky et al 2005 IEEE Trans. Appl. Supercond. 15 1367-70). The ITER conductor design has already been modified compared to the CS insert, to increase the margin and provide increased resistance to the degradation, by using a steel jacket to provide thermal pre-compression to reduce tensile strain levels, reducing the void fraction from 36% to 33% and increasing the non-copper material by 25%. Test results are not yet available for the new design and performance predictions at present rely on models with limited verification.

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.

QUICK RELEASABLE DRIVE

DOEpatents

Dickson, J.J.

1958-07-01

A quick releasable mechanical drive system suitable for use in a nuclear reactor is described. A small reversible motor positions a control rod by means of a worm and gear speed reducer, a magnetic torque clutch, and a bell crank. As the control rod is raised to the operating position, a heavy coil spring is compressed. In the event of an emergency indicated by either a''scram'' signal or a power failure, the current to the magnetic clutch is cut off, thereby freeing the coil spring and the bell crank positioner from the motor and speed reduction gearing. The coil spring will immediately act upon the bell crank to cause the insertion of the control rod. This arrangement will allow the slow, accurate positioning of the control rod during reactor operation, while providing an independent force to rapidly insert the rod in the event of an emergency.

New head gradient coil design and construction techniques.

PubMed

Handler, William B; Harris, Chad T; Scholl, Timothy J; Parker, Dennis L; Goodrich, K Craig; Dalrymple, Brian; Van Sass, Frank; Chronik, Blaine A

2014-05-01

To design and build a head insert gradient coil to use in conjunction with body gradients for superior imaging. The use of the boundary element method to solve for a gradient coil wire pattern on an arbitrary surface allowed us to incorporate engineering changes into the electromagnetic design of a gradient coil directly. Improved wire pattern design was combined with robust manufacturing techniques and novel cooling methods. The finished coil had an efficiency of 0.15 mT/m/A in all three axes and allowed the imaging region to extend across the entire head and upper part of the neck. The ability to adapt an electromagnetic design to necessary changes from an engineering perspective leads to superior coil performance. Copyright © 2013 Wiley Periodicals, Inc.

Dynamic impedance compensation for wireless power transfer using conjugate power

NASA Astrophysics Data System (ADS)

Liu, Suqi; Tan, Jianping; Wen, Xue

2018-02-01

Wireless power transfer (WPT) via coupled magnetic resonances has been in development for over a decade. However, the frequency splitting phenomenon occurs in the over-coupled region. Thus, the output power of the two-coil system achieves the maximum output power at the two splitting angular frequencies, and not at the natural resonant angular frequency. According to the maximum power transfer theorem, the impedance compensation method was adopted in many WPT projects. However, it remains a challenge to achieve the maximum output power and transmission efficiency in a fixed-frequency mode. In this study, dynamic impedance compensation for WPT was presented by utilizing the compensator within a virtual three-coil WPT system. First, the circuit model was established and transfer characteristics of a system were studied by utilizing circuit theories. Second, the power superposition of the WPT system was carefully researched. When a pair of compensating coils was inserted into the transmitter loop, the conjugate power of the compensator loop was created via magnetic coupling of the two compensating coils that insert into the transmitter loop. The mechanism for dynamic impedance compensation for wireless power transfer was then provided by investigating a virtual three-coil WPT system. Finally, the experimental circuit of a virtual three-coil WPT system was designed, and experimental results are consistent with the theoretical analysis, which achieves the maximum output power and transmission efficiency.

Entropy Generation Analysis through Helical Coil Heat Exchanger in an Agitated Vessel

NASA Astrophysics Data System (ADS)

Ashok Reddy, K.

2018-03-01

Entropy Generation have been obtained while conducting the experiments for different sodium carboxymethyl cellulose concentrations 0.05%,0.1%,0.15% and 0.2% of Newtonian and non Newtonian fluids and the data made available by passing the test fluid at different flow rates through a helical coil in a mixing coil using paddle impeller. Heating of fluids depend on operational parameters, geometry of the mixing vessel and the type of impeller used. A new design of heating element was design and fabricated by providing kanthal wire inserted into a glove knitted with fiber glass yarn as glass fabric is flexible, heat resistant and can accommodate to adopt small difference in size of the vessel, perfectly. The knitted fabric is made to the shape of vessel used in the experiment and the heating elements are inserted so that it gets embedded and forms part of the glove knitted with yarn of fiber glass.

DESIGN STUDY OF 20 T, 15 CM BORE HYBRID MAGNET WITH RADIATION RESISTANT INSERT FOR PION CAPTURE.

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

WEGGEL,R.J.; PEARSON,C.E.; KING,B.J.

2001-06-18

To capture pions the Neutrino Factory and Muon Collider Collaboration needs a field of {approx}20 T throughout a cylinder 15 cm in diameter and 60 cm long, falling over the next 18 m to 1.25 T, while the bore increases fourfold inversely as the square root of the field. We propose a hybrid system. The superconducting magnet is of world-class parameters, storing 600 MJ and including a coil to generate 14 T in a bore of {approx}1.3 m. Intercoil forces reach 100 MN. For high radiation resistance, the insert coil is of mineral-insulated hollow conductor, as developed for the Japanmore » Hadron Facility; it would require 12 MW to generate 6 T. Needed is research to develop a more efficient hollow conductor or radiation-resistant insulator for a Bitter coil.« less

Measurement of a Conduction Cooled Nb3Sn Racetrack Coil

NASA Astrophysics Data System (ADS)

Kim, HS; Kovacs, C.; Rochester, J.; Sumption, MD; Tomsic, M.; Peng, X.; Doll, D.

2017-12-01

Use of superconducting coils for wind turbines and electric aircraft is of interest because of the potential for high power density and weight reduction. Here we test a racetrack coil developed as a proof-of-concept for cryogen-free superconducting motors and generators. The coil was wound with 1209 m of 0.7-mm-diameter insulated tube-type Nb3Sn wire. The coil was epoxy-impregnated, instrumented, covered with numerous layers of aluminized mylar insulation, and inserted vertically into a dewar. The system was cooled to 4.2 K, and a few inches of liquid helium was allowed to collect at the bottom of the dewar but below the coil. The coil was cooled by conduction via copper cooling bars were attached to the coil but also were immersed in the liquid helium at their lower ends. Several current tests were performed on the coil, initially in voltage mode, and one run in current mode. The maximum coil Ic at 4.2 K was 480 A, generating 3.06 T at the surface of the coil. The coil met the design targets with a noticeable margin.

New head gradient coil design and construction techniques

PubMed Central

Handler, William B; Harris, Chad T; Scholl, Timothy J; Parker, Dennis L; Goodrich, K Craig; Dalrymple, Brian; Van Sass, Frank; Chronik, Blaine A

2013-01-01

Purpose To design and build a head insert gradient coil to use in conjunction with body gradients for superior imaging. Materials and Methods The use of the Boundary Element Method to solve for a gradient coil wire pattern on an arbitrary surface has allowed us to incorporate engineering changes into the electromagnetic design of a gradient coil directly. Improved wire pattern design has been combined with robust manufacturing techniques and novel cooling methods. Results The finished coil had an efficiency of 0.15 mT/m/A in all three axes and allowed the imaging region to extend across the entire head and upper part of the neck. Conclusion The ability to adapt your electromagnetic design to necessary changes from an engineering perspective leads to superior coil performance. PMID:24123485

A Plasma Focus Device with a 2-MA Discharge Current as a Hard X-Ray Source

NASA Astrophysics Data System (ADS)

Yurkov, D. I.; Dulatov, A. K.; Lemeshko, B. D.; Andreev, D. A.; Golikov, A. V.; Mikhailov, Yu. V.; Prokuratov, I. A.; Selifanov, A. N.; Fatiev, T. S.

2018-04-01

A device based on a pulsed current generator with capacitive energy storage loaded on a plasma focus (PF) chamber is described. The device provides a discharge current amplitude of up to 2 MA in the PF chamber at a stored energy in the capacitor bank of up to 150 kJ. The PF chamber is designed to study hard X-ray (HXR) emission. It has windows for output of HXR emission in the cathode direction, as well as a special insert for output of HXR emission into the anode cavity. A study of operation of the chamber as a part of the setup with the use of various X-ray targets on the anode has been carried out. At a discharge current of 1.5MA, an HXR pulse with an average duration of 16 ns and energy spectrum from 10 to 200 keV, which provides an absorbed dose in the irradiated samples on the order of 1 Sv, is generated in the PF chamber.

High field Nb/sub 3/Sn Axicell insert coils for the Mirror Fusion Test Facility-B (MFTF-B) axicell configuration. Final report

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

Baldi, R.W.; Tatro, R.E.; Scanlan, R.M.

1984-03-01

Two 12-tesla superconducting insert coils are being designed by General Dynamics Convair Division for the axicell regions of MFTF-B for Lawrence Livermore National Laboratory. A major challenge of this project is to ensure that combined fabrication and operational strains induced in the conductor are within stringent limitations of the relatively brittle Nb/sub 3/Sn superconductor filaments. These coils are located in the axicell region of MFTF-B. They have a clear-bore diameter of 36.195cm (14.25 inches) and consist of 27 double pancakes (i.e., 54 pancakes per coil) would on an electrically insulated 304LN stainless steel/bobbin helium vessel. Each pancake has 57 turnsmore » separated by G-10CR insulation. The complete winding bundle has 4.6 million ampere-turns and uniform current density of 2007 A/cm/sup 2/. In conjunction with the other magnets in the system, they produce a 12-tesla central field and a 12.52-tesla peak field. A multifilamentary Nb/sub 3/Sn conductor was selected to meet these requirements. The conductor consists of a monolithic insert soldered into a copper stabilizer. Sufficient cross-sectional area and work-hardening of the copper stabilizer has been provided for the conductor to self-react the electromagnetic Lorentz force induced hoop stresses with normal operational tensile strains less than 0.07 percent.« less

Fields and coupling between coils embedded in conductive environments

NASA Astrophysics Data System (ADS)

Chu, Son; Vallecchi, Andrea; Stevens, Christopher J.; Shamonina, Ekaterina

2018-02-01

An approximate solution is developed for the mutual inductance of two circular coils enclosed by insulating cavities in a conducting medium. This solution is used to investigate the variation of the mutual inductance upon the conductivity of the background (e.g., soil, seawater or human body), as well as upon other parameters such as the vertical of the coils and the displacement of one of the coils in the horizontal plane. Our theoretical results are compared with full wave simulations and a previous solution valid when a conductive slab is inserted between two coupled resonant coils. The proposed approach can have direct impact on the design and optimisation of magnetoinductive waveguides and wireless power transfer for underground/underwater networks and embedded biomedical systems.

Method and means of packaging nuclear fuel rods for handling

DOEpatents

Adam, Milton F.

1979-01-01

Nuclear fuel rods, especially spent nuclear fuel rods that may show physical distortion, are encased within a metallic enclosing structure by forming a tube about the fuel rod. The tube has previously been rolled to form an overlapping tubular structure and then unrolled and coiled about an axis perpendicular to the tube. The fuel rod is inserted into the tube as the rolled tube is removed from a coiled strip and allowed to reassume its tubular shape about the fuel rod. Rollers support the coiled strip in an open position as the coiled strip is uncoiled and allowed to roll about the fuel rod.

Results for diffusion-weighted imaging with a fourth-channel gradient insert.

PubMed

Feldman, Rebecca E; Scholl, Timothy J; Alford, Jamu K; Handler, William B; Harris, Chad T; Chronik, Blaine A

2011-12-01

Diffusion-weighted imaging suffers from motion artifacts and relatively low signal quality due to the long echo times required to permit the diffusion encoding. We investigated the inclusion of a noncylindrical fourth gradient coil, dedicated entirely to diffusion encoding, into the imaging system. Standard three-axis whole body gradients were used during image acquisition, but we designed and constructed an insert coil to perform diffusion encodings. We imaged three phantoms on a 3-T system with a range of diffusion coefficients. Using the insert gradient, we were able to encode b values of greater than 1300 s/mm(2) with an echo time of just 83 ms. Images obtained using the insert gradient had higher signal to noise ratios than those obtained using the whole body gradient: at 500 s/mm(2) there was a 18% improvement in signal to noise ratio, at 1000 s/mm(2) there was a 39% improvement in signal to noise ratio, and at 1350 s/mm(2) there was a 56% improvement in signal to noise ratio. Using the insert gradient, we were capable of doing diffusion encoding at high b values by using relatively short echo times. Copyright © 2011 Wiley Periodicals, Inc.

Molecular basis of coiled-coil oligomerization-state specificity.

PubMed

Ciani, Barbara; Bjelic, Saša; Honnappa, Srinivas; Jawhari, Hatim; Jaussi, Rolf; Payapilly, Aishwarya; Jowitt, Thomas; Steinmetz, Michel O; Kammerer, Richard A

2010-11-16

Coiled coils are extensively and successfully used nowadays to rationally design multistranded structures for applications, including basic research, biotechnology, nanotechnology, materials science, and medicine. The wide range of applications as well as the important functions these structures play in almost all biological processes highlight the need for a detailed understanding of the factors that control coiled-coil folding and oligomerization. Here, we address the important and unresolved question why the presence of particular oligomerization-state determinants within a coiled coil does frequently not correlate with its topology. We found an unexpected, general link between coiled-coil oligomerization-state specificity and trigger sequences, elements that are indispensable for coiled-coil formation. By using the archetype coiled-coil domain of the yeast transcriptional activator GCN4 as a model system, we show that well-established trimer-specific oligomerization-state determinants switch the peptide's topology from a dimer to a trimer only when inserted into the trigger sequence. We successfully confirmed our results in two other, unrelated coiled-coil dimers, ATF1 and cortexillin-1. We furthermore show that multiple topology determinants can coexist in the same trigger sequence, revealing a delicate balance of the resulting oligomerization state by position-dependent forces. Our experimental results should significantly improve the prediction of the oligomerization state of coiled coils. They therefore should have major implications for the rational design of coiled coils and consequently many applications using these popular oligomerization domains.

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.

The MQXA quadrupoles for the LHC low-beta insertions

NASA Astrophysics Data System (ADS)

Ajima, Y.; Higashi, N.; Iida, M.; Kimura, N.; Nakamoto, T.; Ogitsu, T.; Ohhata, H.; Ohuchi, N.; Shintomi, T.; Sugawara, S.; Sugita, K.; Tanaka, K.; Taylor, T.; Terashima, A.; Tsuchiya, K.; Yamamoto, A.

2005-09-01

High-performance superconducting quadrupole magnets, MQXA, for the LHC low-beta insertions have been designed, manufactured in series and tested. The design field gradient of the quadrupole, which has a coil aperture of diameter 70 mm, was 240 T/m at 1.9 K; its effective length is 6.37 m, and it is required to operate reliably at up to 215 T/m when subjected to radiation heat deposit in the coils of up to 5 W/m. The series of 20 magnets has been produced in industry, and tested at KEK. The magnet design is explained, and the construction and performance of the series units, in terms of training, field quality and geometry, are presented.

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

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.

Prospects for Advanced Tokamak Operation of ITER

NASA Astrophysics Data System (ADS)

Neilson, George H.

1996-11-01

Previous studies have identified steady-state (or "advanced") modes for ITER, based on reverse-shear profiles and significant bootstrap current. A typical example has 12 MA of plasma current, 1,500 MW of fusion power, and 100 MW of heating and current-drive power. The implementation of these and other steady-state operating scenarios in the ITER device is examined in order to identify key design modifications that can enhance the prospects for successfully achieving advanced tokamak operating modes in ITER compatible with a single null divertor design. In particular, we examine plasma configurations that can be achieved by the ITER poloidal field system with either a monolithic central solenoid (as in the ITER Interim Design), or an alternate "hybrid" central solenoid design which provides for greater flexibility in the plasma shape. The increased control capability and expanded operating space provided by the hybrid central solenoid allows operation at high triangularity (beneficial for improving divertor performance through control of edge-localized modes and for increasing beta limits), and will make it much easier for ITER operators to establish an optimum startup trajectory leading to a high-performance, steady-state scenario. Vertical position control is examined because plasmas made accessible by the hybrid central solenoid can be more elongated and/or less well coupled to the conducting structure. Control of vertical-displacements using the external PF coils remains feasible over much of the expanded operating space. Further work is required to define the full spectrum of axisymmetric plasma disturbances requiring active control In addition to active axisymmetric control, advanced tokamak modes in ITER may require active control of kink modes on the resistive time scale of the conducting structure. This might be accomplished in ITER through the use of active control coils external to the vacuum vessel which are actuated by magnetic sensors near the first wall. The enhanced shaping and positioning flexibility provides a range of options for reducing the ripple-induced losses of fast alpha particles--a major limitation on ITER steady-state modes. An alternate approach that we are pursuing in parallel is the inclusion of ferromagnetic inserts to reduce the toroidal field ripple within the plasma chamber. The inclusion of modest design changes such as the hybrid central solenoid, active control coils for kink modes, and ferromagnetic inserts for TF ripple reduction show can greatly increase the flexibility to accommodate advance tokamak operation in ITER. Increased flexibility is important because the optimum operating scenario for ITER cannot be predicted with certainty. While low-inductance, reverse shear modes appear attractive for steady-state operation, high-inductance, high-beta modes are also viable candidates, and it is important that ITER have the flexibility to explore both these, and other, operating regimes.

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

Fabbricatore, P.; Ambrosio, G.; Cheban, S.

The Mu2e Transport Solenoid consists of 52 coils arranged in 27 coil modules that form the S-shaped cold mass. Each coil is wound from Al-stabilized NbTi superconductor. The coils are supported by an external structural aluminum shell machined from a forged billet. Most of the coil modules house two coils, with the axis of each coil oriented at an angle of approximately 5° with respect to each other. The coils are indirectly cooled with LHe circulating in tubes welded on the shell. In order to enhance the cooling capacity, pure aluminum sheets connect the inner bore of the coils tomore » the cooling tubes. The coils are placed inside the shell by the means of a shrink-fit procedure. A full-size prototype, with all the features of the full assembly, was successfully manufactured in a collaboration between INFN Genova and Fermilab. In order to ensure an optimal mechanical prestress at the coil-shell interface, the coils are inserted into the shell through a shrink-fitting process. We present the details of the prototype with the design choices as validated by the structural analysis. In conclusion, the fabrication steps are described as well.« less

Mu2e transport solenoid prototype design and manufacturing

DOE PAGES

Fabbricatore, P.; Ambrosio, G.; Cheban, S.; ...

2016-02-08

The Mu2e Transport Solenoid consists of 52 coils arranged in 27 coil modules that form the S-shaped cold mass. Each coil is wound from Al-stabilized NbTi superconductor. The coils are supported by an external structural aluminum shell machined from a forged billet. Most of the coil modules house two coils, with the axis of each coil oriented at an angle of approximately 5° with respect to each other. The coils are indirectly cooled with LHe circulating in tubes welded on the shell. In order to enhance the cooling capacity, pure aluminum sheets connect the inner bore of the coils tomore » the cooling tubes. The coils are placed inside the shell by the means of a shrink-fit procedure. A full-size prototype, with all the features of the full assembly, was successfully manufactured in a collaboration between INFN Genova and Fermilab. In order to ensure an optimal mechanical prestress at the coil-shell interface, the coils are inserted into the shell through a shrink-fitting process. We present the details of the prototype with the design choices as validated by the structural analysis. In conclusion, the fabrication steps are described as well.« less

Suprapatellar Versus Infrapatellar Tibial Nail Insertion: A Prospective Randomized Control Pilot Study.

PubMed

Chan, Daniel S; Serrano-Riera, Rafael; Griffing, Rebecca; Steverson, Barbara; Infante, Anthony; Watson, David; Sagi, H Claude; Sanders, Roy W

2016-03-01

The purpose of this OTA-approved pilot study was to compare the clinical and functional outcomes of the knee joint after infrapatellar (IP) versus suprapatellar (SP) tibial nail insertion. Prospective, randomized. Level I trauma center. After institutional review board approval, skeletally mature patients with OTA 42 tibial shaft fractures were randomized into either an IP or SP nail insertion group after informed consent was obtained. The SP also underwent prenail and postnail insertion patella-femoral (PF) joint arthroscopy. Patients underwent follow-up (6 weeks, 3, 6, and 12 months) with standard radiographs, as well as visual analog score and pain diagram documentation. At the 6-month and 12-month visits, knee function questionnaires (Lysholm knee scale and SF-36) were completed. Magnetic resonance imaging/image (MRI) of the affected knee was obtained at 12 months. Ten patients in each group were required for a power analysis for the anticipated larger randomized control trial, but enrollment in each arm was not limited because of known problems with patient follow-up over a 12-month period. A total of 41 patients/fractures were enrolled in this study. Of those, only 25 patients/fractures (14 IP, 11 SP) fully complied with and completed 12 months of follow-up. Six of 11 SP presented with articular changes (chondromalacia) in the PF joint during the preinsertion arthroscopy. Three patients displayed a change in the articular cartilage based on postnail insertion arthroscopy. At 12 months, all fractures in both groups had proceeded to union. There were no differences between the affected and unaffected knee with respect to range of motion. Functional visual analog score and Lysholm knee scores showed no significant differences between groups (P > 0.05). The SF-36v2 comparison also revealed no significant differences in the overall score, all 4 mental components, and 3/4 physical components (P > 0.05). The bodily pain component score was superior in the SP group (45 vs. 36, P = 0.035). All 11 SP patients obtained MRIs at 1 year. Five of these patients had evidence of chondromalacia on MRI. These findings did not correlate with either the prenail or postnail insertion arthroscopy. Importantly, no patient in the SP group with postnail insertion arthroscopic changes had PF joint pain at 1 year. Overall, there seemed to be no significant differences in pain, disability, or knee range of motion between these 2 tibial intramedullary nail insertion techniques after 12 months of follow-up. Based on this pilot study data, larger prospective trial with long-term follow-up is warranted. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Facial asymmetry and clinical manifestations in patients with novel insertion of the TCOF1 gene.

PubMed

Su, P-H; Liu, Y-F; Yu, J-S; Chen, J-Y; Chen, S-J; Lai, Y-J

2012-11-01

This study explored the role of TCOF1 insertion mutations in Taiwanese patients with craniofacial anomalies. Twelve patients with single or multiple, asymmetrical congenital craniofacial anomalies were enrolled. Genomic DNA was prepared from leukocytes; the coding regions of TCOF1 were analyzed by polymerase chain reaction and direct sequencing. Clinical manifestations were correlated to the TCOF1 mutation. Six of 12 patients diagnosed with hemifacial microsomia exhibited a novel insertion mutation 4127 ins G (frameshift) in exon 24 in the TCOF1 gene. All six patients were diagnosed with anomalies on the left side. In addition, four of these six patients had hearing impairment; three had other major anomalies; and two had developmental delay. The insertion caused a frameshift, an early truncation, the loss of two putative nuclear localization signals (residues 1404-1420 and 1424-1440), and the loss of coiled coil domain (1406-1426) in treacle protein. These findings support the existence of two regulators of growth of the mandibular condyles. © 2011 John Wiley & Sons A/S.

Eddy current measurement of tube element spacing

DOEpatents

Latham, Wayne Meredith; Hancock, Jimmy Wade; Grut, Jayne Marie

1998-01-01

A method of electromagnetically measuring the distance between adjacent tube elements in a heat exchanger. A cylindrical, high magnetic permeability ferrite slug is placed in the tube adjacent the spacing to be measured. A bobbin or annular coil type probe operated in the absolute mode is inserted into a second tube adjacent the spacing to be measured. From prior calibrations on the response of the eddy current coil, the signals from the coil, when sensing the presence of the ferrite slug, are used to determine the spacing between the tubes.

Superelliptical insert gradient coil with a field-modifying layer for breast imaging.

PubMed

Moon, Sung M; Goodrich, K Craig; Hadley, J Rock; Kim, Seong-Eun; Zeng, Gengsheng L; Morrell, Glen R; McAlpine, Matthew A; Chronik, Blaine A; Parker, Dennis L

2011-03-01

Many MRI applications such as dynamic contrast-enhanced MRI of the breast require high spatial and temporal resolution and can benefit from improved gradient performance, e.g., increased gradient strength and reduced gradient rise time. The improved gradient performance required to achieve high spatial and temporal resolution for this application may be achieved by using local insert gradients specifically designed for a target anatomy. Current flat gradient systems cannot create an imaging volume large enough to accommodate both breasts; further, their gradient fields are not homogeneous, dropping off rapidly with distance from the gradient coil surface. To attain an imaging volume adequate for bilateral breast MRI, a planar local gradient system design has been modified into a superellipse shape, creating homogeneous gradient volumes that are 182% (Gx), 57% (Gy), and 75% (Gz) wider (left/right direction) than those of the corresponding standard planar gradient. Adding an additional field-modifying gradient winding results in an additional improvement of the homogeneous gradient field near the gradient coil surface over the already enlarged homogeneous gradient volumes of the superelliptical gradients (67%, 89%, and 214% for Gx, Gy, and Gz respectively). A prototype y-gradient insert has been built to demonstrate imaging and implementation characteristics of the superellipse gradient in a 3 T MRI system. Copyright © 2010 Wiley-Liss, Inc.

Method Of Wire Insertion For Electric Machine Stators

DOEpatents

Brown, David L; Stabel, Gerald R; Lawrence, Robert Anthony

2005-02-08

A method of inserting coils in slots of a stator is provided. The method includes interleaving a first set of first phase windings and a first set of second phase windings on an insertion tool. The method also includes activating the insertion tool to radially insert the first set of first phase windings and the first set of second phase windings in the slots of the stator. In one embodiment, interleaving the first set of first phase windings and the first set of second phase windings on the insertion tool includes forming the first set of first phase windings in first phase openings defined in the insertion tool, and forming the first set of second phase windings in second phase openings defined in the insertion tool.

Low-noise magnetometer based on inductance modulation in high-critical-temperature superconductor coil

NASA Astrophysics Data System (ADS)

Enpuku, Keiji; Matsuo, Masaaki; Yoshida, Yujiro; Yamashita, Shigeya; Sasayama, Teruyoshi; Yoshida, Takashi

2018-06-01

We developed a magnetometer based on inductance modulation of a coil made from a high-critical-temperature superconducting material. The coil inductance was modulated over time via a modulation current applied to a magnetic wire that was inserted into the coil. The magnetic field was then converted into a signal voltage using this time-dependent inductance. The relationship between magnetometer performance and the modulation current conditions was studied. Under appropriate conditions, the magnetometer had responsivity of 885 V/T. The magnetic field noise was 1.3 pT/Hz1/2 in the white noise region and 5.6 pT/Hz1/2 at f = 1 Hz.

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.

Telomerase-mediated life-span extension of human primary fibroblasts by human artificial chromosome (HAC) vector

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

Shitara, Shingo; Kakeda, Minoru; Nagata, Keiko

2008-05-09

Telomerase-mediated life-span extension enables the expansion of normal cells without malignant transformation, and thus has been thought to be useful in cell therapies. Currently, integrating vectors including the retrovirus are used for human telomerase reverse transcriptase (hTERT)-mediated expansion of normal cells; however, the use of these vectors potentially causes unexpected insertional mutagenesis and/or activation of oncogenes. Here, we established normal human fibroblast (hPF) clones retaining non-integrating human artificial chromosome (HAC) vectors harboring the hTERT expression cassette. In hTERT-HAC/hPF clones, we observed the telomerase activity and the suppression of senescent-associated SA-{beta}-galactosidase activity. Furthermore, the hTERT-HAC/hPF clones continued growing beyond 120 daysmore » after cloning, whereas the hPF clones retaining the silent hTERT-HAC senesced within 70 days. Thus, hTERT-HAC-mediated episomal expression of hTERT allows the extension of the life-span of human primary cells, implying that gene delivery by non-integrating HAC vectors can be used to control cellular proliferative capacity of primary cultured cells.« less

Overproduction, purification and crystallization of a chondroitin sulfate A-binding DBL domain from a Plasmodium falciparum var2csa-encoded PfEMP1 protein

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

Higgins, Matthew K., E-mail: mkh20@cam.ac.uk

A chondroitin sulfate A-binding DBL important in placental malaria has been overproduced, purified and crystallized. Diffraction data were collected to 1.9 Å resolution. The PfEMP1 proteins of the malaria parasite Plasmodium falciparum are inserted into the membrane of infected red blood cells, where they mediate adhesion to a variety of human receptors. The DBL domains of the var2csa-encoded PfEMP1 protein play a critical role in malaria of pregnancy, tethering infected cells to the surface of the placenta through interactions with the glycosaminoglycan carbohydrate chondroitin sulfate A (CSA). A CSA-binding DBL domain has been overproduced in a bacterial expression system, purifiedmore » and crystallized. Native data sets extending to 1.9 Å resolution have been collected and phasing is under way.« less

Synthesis, characterisation and applications of coiled carbon nanotubes.

PubMed

Hanus, Monica J; Harris, Andrew T

2010-04-01

Coiled carbon nanotubes are helical carbon structures formed when heptagonal and pentagonal rings are inserted into the hexagonal backbone of a 'straight' nanotube. Coiled carbon nanotubes have been reported with both regular and irregular helical structures. In this work the structure, growth mechanism(s), synthesis, properties and potential applications of coiled carbon nanotubes are reviewed. Published data suggests that coiled carbon nanotube synthesis occurs due to nonuniform extrusion of carbon from a catalyst surface. To date, coiled carbon nanotubes have been synthesised using catalyst modification techniques including: (i) the addition of S or P containing compounds during synthesis; (ii) the use of binary or ternary metal catalysts; (iii) the use of microwaves to create a local temperature gradient around individual catalyst particles and; (iv) the use of pH control during catalyst preparation. In most instances coiled carbon nanotubes are produced as a by-product; high yield and/or large-scale synthesis of coiled carbon nanotubes remains problematic. The qualitative analysis of coiled carbon nanotubes is currently hindered by the absence of specific characterisation data in the literature, e.g., oxidation profiles measured by thermogravimetric analysis and Raman spectra of pure coiled carbon nanotube samples.

Bioinformatics analysis for structure and function of CPR of Plasmodium falciparum.

PubMed

Fan, Zhigang; Zhang, Lingmin; Yan, Guogang; Wu, Qiang; Gan, Xiufeng; Zhong, Saifeng; Lin, Guifen

2011-02-01

To analyse the structure and function of NADPH-cytochrome p450 reductase (CYPOR or CPR) from Plasmodium falciparum (Pf), and to predict its' drug target and vaccine target. The structure, function, drug target and vaccine target of CPR from Plasmodium falciparum were analyzed and predicted by bioinformatics methods. PfCPR, which was older CPR, had close relationship with the CPR from other Plasmodium species, but it was distant from its hosts, such as Homo sapiens and Anopheles. PfCPR was located in the cellular nucleus of Plasmodium falciparum. 335aa-352aa and 591aa - 608aa were inserted the interior side of the nuclear membrane, while 151aa-265aa was located in the nucleolus organizer regions. PfCPR had 40 function sites and 44 protein-protein binding sites in amino acid sequence. The teriary structure of 1aa-700aa was forcep-shaped with wings. 15 segments of PfCPR had no homology with Homo sapien CPR and most were exposed on the surface of the protein. These segments had 25 protein-protein binding sites. While 13 other segments all possessed function sites. The evolution or genesis of Plasmodium falciparum is earlier than those of Homo sapiens. PfCPR is a possible resistance site of antimalarial drug and may involve immune evasion, which is associated with parasite of sporozoite in hepatocytes. PfCPR is unsuitable as vaccine target, but it has at least 13 ideal drug targets. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

An Analytical Technique to Elucidate Field Impurities From Manufacturing Uncertainties of an Double Pancake Type HTS Insert for High Field LTS/HTS NMR Magnets

PubMed Central

Hahn, Seung-yong; Ahn, Min Cheol; Bobrov, Emanuel Saul; Bascuñán, Juan; Iwasa, Yukikazu

2010-01-01

This paper addresses adverse effects of dimensional uncertainties of an HTS insert assembled with double-pancake coils on spatial field homogeneity. Each DP coil was wound with Bi2223 tapes having dimensional tolerances larger than one order of magnitude of those accepted for LTS wires used in conventional NMR magnets. The paper presents: 1) dimensional variations measured in two LTS/HTS NMR magnets, 350 MHz (LH350) and 700 MHz (LH700), both built and operated at the Francis Bitter Magnet Laboratory; and 2) an analytical technique and its application to elucidate the field impurities measured with the two LTS/HTS magnets. Field impurities computed with the analytical model and those measured with the two LTS/HTS magnets agree quite well, demonstrating that this analytical technique is applicable to design a DP-assembled HTS insert with an improved field homogeneity for a high-field LTS/HTS NMR magnet. PMID:20407595

ACCELERATOR TARGET POSITIONER AND CONTROL CIRCUIT THEREFOR

DOEpatents

Stone, K.F.; Force, R.J.; Olson, W.W.; Cagle, D.S.

1959-12-15

An apparatus is described for inserting and retracting a target material with respect to the internal beam of a charged particle accelerator and to circuitry for controlling the timing and motion of the target placement. Two drive coils are mounted on the shaft of a target holder arm and disposed within the accelerator magnetic field with one coil at right angles to the other. Control circuitry alternately connects each coil to a current source and to a varying shorting resistance whereby the coils interchangeably produce driving and braking forces which swing the target arm within a ninety degree arc. The target is thus moved into the beam and away from it at high speeds and is brought to rest after each movement without whiplash or vibration.

Drilling jar for use in a downhole network

DOEpatents

Hall, David R.; Fox, Joe; McPherson, James; Pixton, David S.; Briscoe, Michael

2006-01-31

Apparatus and methods for integrating transmission cable into the body of selected downhole tools, such as drilling jars, having variable or changing lengths. A wired downhole-drilling tool is disclosed in one embodiment of the invention as including a housing and a mandrel insertable into the housing. A coiled cable is enclosed within the housing and has a first end connected to the housing and a second end connected to the mandrel. The coiled cable is configured to stretch and shorten in accordance with axial movement between the housing and the mandrel. A clamp is used to fix the coiled cable with respect to the housing, the mandrel, or both, to accommodate a change of tension in the coiled cable.

PET Performance Evaluation of an MR-Compatible PET Insert

PubMed Central

Wu, Yibao; Catana, Ciprian; Farrell, Richard; Dokhale, Purushottam A.; Shah, Kanai S.; Qi, Jinyi; Cherry, Simon R.

2010-01-01

A magnetic resonance (MR) compatible positron emission tomography (PET) insert has been developed in our laboratory for simultaneous small animal PET/MR imaging. This system is based on lutetium oxyorthosilicate (LSO) scintillator arrays with position-sensitive avalanche photodiode (PSAPD) photodetectors. The PET performance of this insert has been measured. The average reconstructed image spatial resolution was 1.51 mm. The sensitivity at the center of the field of view (CFOV) was 0.35%, which is comparable to the simulation predictions of 0.40%. The average photopeak energy resolution was 25%. The scatter fraction inside the MRI scanner with a line source was 12% (with a mouse-sized phantom and standard 35 mm Bruker 1H RF coil), 7% (with RF coil only) and 5% (without phantom or RF coil) for an energy window of 350–650 keV. The front-end electronics had a dead time of 390 ns, and a trigger extension dead time of 7.32 μs that degraded counting rate performance for injected doses above ~0.75 mCi (28 MBq). The peak noise-equivalent count rate (NECR) of 1.27 kcps was achieved at 290 μCi (10.7 MBq). The system showed good imaging performance inside a 7-T animal MRI system; however improvements in data acquisition electronics and reduction of the coincidence timing window are needed to realize improved NECR performance. PMID:21072320

Reliability of Various Measurement Stations for Determining Plantar Fascia Thickness and Echogenicity.

PubMed

Bisi-Balogun, Adebisi; Cassel, Michael; Mayer, Frank

2016-04-13

This study aimed to determine the relative and absolute reliability of ultrasound (US) measurements of the thickness and echogenicity of the plantar fascia (PF) at different measurement stations along its length using a standardized protocol. Twelve healthy subjects (24 feet) were enrolled. The PF was imaged in the longitudinal plane. Subjects were assessed twice to evaluate the intra-rater reliability. A quantitative evaluation of the thickness and echogenicity of the plantar fascia was performed using Image J, a digital image analysis and viewer software. A sonography evaluation of the thickness and echogenicity of the PF showed a high relative reliability with an Intra class correlation coefficient of ≥0.88 at all measurement stations. However, the measurement stations for both the PF thickness and echogenicity which showed the highest intraclass correlation coefficient (ICCs) did not have the highest absolute reliability. Compared to other measurement stations, measuring the PF thickness at 3 cm distal and the echogenicity at a region of interest 1 cm to 2 cm distal from its insertion at the medial calcaneal tubercle showed the highest absolute reliability with the least systematic bias and random error. Also, the reliability was higher using a mean of three measurements compared to one measurement. To reduce discrepancies in the interpretation of the thickness and echogenicity measurements of the PF, the absolute reliability of the different measurement stations should be considered in clinical practice and research rather than the relative reliability with the ICC.

Reliability of Various Measurement Stations for Determining Plantar Fascia Thickness and Echogenicity

PubMed Central

Bisi-Balogun, Adebisi; Cassel, Michael; Mayer, Frank

2016-01-01

This study aimed to determine the relative and absolute reliability of ultrasound (US) measurements of the thickness and echogenicity of the plantar fascia (PF) at different measurement stations along its length using a standardized protocol. Twelve healthy subjects (24 feet) were enrolled. The PF was imaged in the longitudinal plane. Subjects were assessed twice to evaluate the intra-rater reliability. A quantitative evaluation of the thickness and echogenicity of the plantar fascia was performed using Image J, a digital image analysis and viewer software. A sonography evaluation of the thickness and echogenicity of the PF showed a high relative reliability with an Intra class correlation coefficient of ≥0.88 at all measurement stations. However, the measurement stations for both the PF thickness and echogenicity which showed the highest intraclass correlation coefficient (ICCs) did not have the highest absolute reliability. Compared to other measurement stations, measuring the PF thickness at 3 cm distal and the echogenicity at a region of interest 1 cm to 2 cm distal from its insertion at the medial calcaneal tubercle showed the highest absolute reliability with the least systematic bias and random error. Also, the reliability was higher using a mean of three measurements compared to one measurement. To reduce discrepancies in the interpretation of the thickness and echogenicity measurements of the PF, the absolute reliability of the different measurement stations should be considered in clinical practice and research rather than the relative reliability with the ICC. PMID:27089369

Nuclear factor of activated T cells (NFAT) in pearl oyster Pinctada fucata: molecular cloning and functional characterization.

PubMed

Huang, Xian-De; Wei, Guo-jian; Zhang, Hua; He, Mao-Xian

2015-01-01

Nuclear factor of activated T cells (NFAT) plays an important role in nonimmune cells and also in T cells and many other cells of the immune system, by regulating the expression of a variety of genes involved in the immune response, organ development, developmental apoptosis and angiogenesis. In the present study, the NFAT homology gene, PfNFAT, from the pearl oyster Pinctada fucata was cloned and its genomic structure and promoter were analyzed. PfNFAT encodes a putative protein of 1226 amino acids, and contains a highly conserved Rel homology region (RHR) with DNA-binding specificity, and a regulatory domain (NFAT homology region, NHR) containing a potent transactivation domain (TAD). The PfNFAT gene consists of 12 exons and 11 introns, and its promoter contains potential binding sites for transcription factors such as NF-κB (Nuclear factor κB), STATx (signal transducer and activator of transcription), AP-1 (activator protein-1) and Sox-5/9 (SRY type HMG box-5/9), MyoD (Myogenic Differentiation Antigen) and IRF (Interferon regulatory factor). Comparison and phylogenetic analysis revealed that PfNFAT shows high identity with other invertebrate NFAT, and clusters with the NFAT5 subgroup. Furthermore, gene expression analysis revealed that PfNFAT is involved in the immune response to lipopolysaccharide (LPS) and Polyinosinic-polycytidylic acid (poly I:C) stimulation and in the nucleus inserting operation. The study of PfNFAT may increase understanding of molluscan innate immunity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Improved Separations of Proteins and Sugar Derivatives Using the Small-Scale Cross-Axis Coil Planet Centrifuge with Locular Multilayer Coiled Columns.

PubMed

Shinomiya, Kazufusa; Umezawa, Motoki; Seki, Manami; Nitta, Jun; Zaima, Kazumasa; Harikai, Naoki; Ito, Yoichiro

2016-12-01

Countercurrent chromatography (CCC) is liquid-liquid partition chromatography without using a solid support matrix. This technique requires further improvement of partition efficiency and shortening theseparation time. The locular multilayer coils modified with and without mixer glass beads were developed for the separation of proteins and 4-methylumbelliferyl (MU) sugar derivatives using the small-scale cross-axis coil planet centrifuge. Proteins were well separated from each other and the separation was improved at a low flow rate of the mobile phase. On the other hand, 4-MU sugar derivatives were sufficiently resolved with short separation time at a highflow rate of the mobile phase under satisfactory stationary phase retention. Effective separations were achieved using the locular multilayer coil for proteins with aqueous-aqueous polymer phase systems and for 4-MU sugar derivatives with organic-aqueous two-phase solvent systems by inserting a glass bead into each locule.

Shape memory polymer (SMP) gripper with a release sensing system

DOEpatents

Maitland, Duncan J.; Lee, Abraham P.; Schumann, Daniel L.; Silva, Luiz Da

2000-01-01

A system for releasing a target material, such as an embolic coil from an SMP located at the end of a catheter utilizing an optical arrangement for releasing the material. The system includes a laser, laser driver, display panel, photodetector, fiber optics coupler, fiber optics and connectors, a catheter, and an SMP-based gripper, and includes a release sensing and feedback arrangement. The SMP-based gripper is heated via laser light through an optic fiber causing the gripper to release a target material (e.g., embolic coil for therapeutic treatment of aneurysms). Various embodiments are provided for coupling the laser light into the SMP, which includes specific positioning of the coils, removal of the fiber cladding adjacent the coil, a metal coating on the SMP, doping the SMP with a gradient absorbing dye, tapering the fiber optic end, coating the SMP with low refractive index material, and locating an insert between the fiber optic and the coil.

The Chlamydomonas Dhc1 gene encodes a dynein heavy chain subunit required for assembly of the I1 inner arm complex.

PubMed Central

Myster, S H; Knott, J A; O'Toole, E; Porter, M E

1997-01-01

Multiple members of the dynein heavy chain (Dhc) gene family have been recovered in several organisms, but the relationships between these sequences and the Dhc isoforms that they encode are largely unknown. To identify Dhc loci and determine the specific functions of the individual Dhc isoforms, we have screened a collection of motility mutants generated by insertional mutagenesis in Chlamydomonas. In this report, we characterize one strain, pf9-3, in which the insertion event was accompanied by a deletion of approximately 13 kb of genomic DNA within the transcription unit of the Dhc1 gene. Northern blot analysis confirms that pf9-3 is a null mutation. Biochemical and structural studies of isolated axonemes demonstrate that the pf9-3 mutant fails to assemble the I1 inner arm complex, a two-headed dynein isoform composed of two Dhcs (1 alpha and 1 beta) and three intermediate chains. To determine if the Dhc1 gene product corresponds to one of the Dhcs of the I1 complex, antibodies were generated against a Dhc1-specific peptide sequence. Immunoblot analysis reveals that the Dhc1 gene encodes the 1 alpha Dhc subunit. These studies thus, identify the first inner arm Dhc locus to be described in any organism and further demonstrate that the 1 alpha Dhc subunit plays an essential role in the assembly of the I1 inner arm complex. Images PMID:9247642

Influence of wire-coil inserts on the thermo-hydraulic performance of a flat-plate solar collector

NASA Astrophysics Data System (ADS)

Herrero Martín, R.; García, A.; Pérez-García, J.

2012-11-01

Enhancement techniques can be applied to flat-plate liquid solar collectors towards more compact and efficient designs. For the typical operating mass flow rates in flat-plate solar collectors, the most suitable technique is inserted devices. Based on previous studies from the authors, wire coils were selected for enhancing heat transfer. This type of inserted device provides better results in laminar, transitional and low turbulence fluid flow regimes. To test the enhanced solar collector and compare with a standard one, an experimental side-by-side solar collector test bed was designed and constructed. The testing set up was fully designed following the requirements of EN12975-2 and allow us to accomplish performance tests under the same operating conditions (mass flow rate, inlet fluid temperature and weather conditions). This work presents the thermal efficiency curves of a commercial and an enhanced solar collector, for the standardized mass flow rate per unit of absorber area of 0.02 kg/sm2 (in useful engineering units 144 kg/h for water as working fluid and 2 m2 flat-plate solar collector of absorber area). The enhanced collector was modified inserting spiral wire coils of dimensionless pitch p/D = 1 and wire-diameter e/D = 0.0717. The friction factor per tube has been computed from the overall pressure drop tests across the solar collectors. The thermal efficiency curves of both solar collectors, a standard and an enhanced collector, are presented. The enhanced solar collector increases the thermal efficiency by 15%. To account for the overall enhancement a modified performance evaluation criterion (R3m) is proposed. The maximum value encountered reaches 1.105 which represents an increase in useful power of 10.5% for the same pumping power consumption.

Clinical Utility of Ultrasound Measurements of Plantar Fascia Width and Cross-Sectional AreaA Novel Technique.

PubMed

Bisi-Balogun, Adebisi; Rector, Michael

2017-09-01

We sought to develop a standardized protocol for ultrasound (US) measurements of plantar fascia (PF) width and cross-sectional area (CSA), which may serve as additional outcome variables during US examinations of both healthy asymptomatic PF and in plantar fasciopathy and determine its interrater and intrarater reliability. Ten healthy individuals (20 feet) were enrolled. Participants were assessed twice by two raters each to determine intrarater and interrater reliability. For each foot, three transverse scans of the central bundle of the PF were taken at its insertion at the medial calcaneal tubercle, identified in real time on the plantar surface of the foot, using a fine wire technique. Reliability was determined using intraclass correlation coefficients (ICC), standard errors of measurement (SEM), and limits of agreement (LOA) expressed as percentages of the mean. Reliability of PF width and CSA measurements was determined using PF width and CSA measurements from one sonogram measured once and the mean of three measurements from three sonograms each measured once. Ultrasound measurements of PF width and CSA showed a mean of 18.6 ± 2.0 mm and 69.20 ± 13.6 mm 2 respectively. Intra-reliability within both raters showed an ICC > 0.84 for width and ICC > 0.92 for CSA as well as a SEM% and LOA% < 10% for both width and CSA. Inter-rater reliability showed an ICC of 0.82 for width and 0.87 for CSA as well as a SEM% and LOA% < 10% for width and a SEM% < 10% and LOA% < 20% for CSA. Relative and absolute reliability within and between raters were higher when using the mean of three sonographs compared to one sonograph. Using this novel technique, PF CSA and width may be determined reliably using measurements from one sonogram or the mean of three sonograms. Measurement of PF CSA and width in addition to already established thickness and echogenicity measurements provides additional information on structural properties of the PF for clinicians and researchers in healthy and pathologic PF.

Optimization of Coil Element Configurations for a Matrix Gradient Coil.

PubMed

Kroboth, Stefan; Layton, Kelvin J; Jia, Feng; Littin, Sebastian; Yu, Huijun; Hennig, Jurgen; Zaitsev, Maxim

2018-01-01

Recently, matrix gradient coils (also termed multi-coils or multi-coil arrays) were introduced for imaging and B 0 shimming with 24, 48, and even 84 coil elements. However, in imaging applications, providing one amplifier per coil element is not always feasible due to high cost and technical complexity. In this simulation study, we show that an 84-channel matrix gradient coil (head insert for brain imaging) is able to create a wide variety of field shapes even if the number of amplifiers is reduced. An optimization algorithm was implemented that obtains groups of coil elements, such that a desired target field can be created by driving each group with an amplifier. This limits the number of amplifiers to the number of coil element groups. Simulated annealing is used due to the NP-hard combinatorial nature of the given problem. A spherical harmonic basis set up to the full third order within a sphere of 20-cm diameter in the center of the coil was investigated as target fields. We show that the median normalized least squares error for all target fields is below approximately 5% for 12 or more amplifiers. At the same time, the dissipated power stays within reasonable limits. With a relatively small set of amplifiers, switches can be used to sequentially generate spherical harmonics up to third order. The costs associated with a matrix gradient coil can be lowered, which increases the practical utility of matrix gradient coils.

Intravascular Placement of Metallic Coils as Lung Tumor Markers for CyberKnife Stereotactic Radiation Therapy.

PubMed

Karaman, Kutlay; Dokdok, A Murat; Karadeniz, Oktay; Ceylan, Cemile; Engin, Kayıhan

2015-01-01

To present our experience with placing endovascular coils in pulmonary arteries used as a fiducial marker for CyberKnife therapy and to describe the technical details and complications of the procedure. Between June 2005 and September 2013, 163 patients with primary or secondary lung malignancies, referred for fiducial placement for stereotactic radiosurgery, were retrospectively reviewed. Fourteen patients (9 men, 5 women; mean age, 70 years) with a history of pneumonectomy (n = 3), lobectomy (n = 3) or with severe cardiopulmonary co-morbidity (n = 8) underwent coil (fiducial marker) placement. Pushable or detachable platinum micro coils (n = 49) 2-3 mm in size were inserted through coaxial microcatheters into a small distal pulmonary artery in the vicinity of the tumor under biplane angiography/fluoroscopy guidance. Forty nine coils with a median number of 3 coils per tumor were placed with a mean tumor-coil distance of 2.7 cm. Forty three (87.7%) of 49 coils were successfully used as fiducial markers. Two coils could not be used due to a larger tumor-coil distance (> 50 mm). Four coils were in an acceptable position but their non-coiling shape precluded tumor tracking for CyberKnife treatment. No major complications needing further medication other than nominal therapy, hospitalization more than one night or permanent adverse sequale were observed. Endovascular placement of coil as a fiducial marker is safe and feasible during CyberKnife therapy, and might be an option for the patients in which percutaneous transthoracic fiducial placement might be risky.

Structural mapping of the coiled-coil domain of a bacterial condensin and comparative analyses across all domains of life suggest conserved features of SMC proteins.

PubMed

Waldman, Vincent M; Stanage, Tyler H; Mims, Alexandra; Norden, Ian S; Oakley, Martha G

2015-06-01

The structural maintenance of chromosomes (SMC) proteins form the cores of multisubunit complexes that are required for the segregation and global organization of chromosomes in all domains of life. These proteins share a common domain structure in which N- and C- terminal regions pack against one another to form a globular ATPase domain. This "head" domain is connected to a central, globular, "hinge" or dimerization domain by a long, antiparallel coiled coil. To date, most efforts for structural characterization of SMC proteins have focused on the globular domains. Recently, however, we developed a method to map interstrand interactions in the 50-nm coiled-coil domain of MukB, the divergent SMC protein found in γ-proteobacteria. Here, we apply that technique to map the structure of the Bacillus subtilis SMC (BsSMC) coiled-coil domain. We find that, in contrast to the relatively complicated coiled-coil domain of MukB, the BsSMC domain is nearly continuous, with only two detectable coiled-coil interruptions. Near the middle of the domain is a break in coiled-coil structure in which there are three more residues on the C-terminal strand than on the N-terminal strand. Close to the head domain, there is a second break with a significantly longer insertion on the same strand. These results provide an experience base that allows an informed interpretation of the output of coiled-coil prediction algorithms for this family of proteins. A comparison of such predictions suggests that these coiled-coil deviations are highly conserved across SMC types in a wide variety of organisms, including humans. © 2015 Wiley Periodicals, Inc.

Analysis and quantification of endovascular coil distribution inside saccular aneurysms using histological images.

PubMed

Morales, Hernán G; Larrabide, Ignacio; Geers, Arjan J; Dai, Daying; Kallmes, David F; Frangi, Alejandro F

2013-11-01

Endovascular coiling is often performed by first placing coils along the aneurysm wall to create a frame and then by filling up the aneurysm core. However, little attention has been paid to quantifying this filling strategy and to see how it changes for different packing densities. The purpose of this work is to analyze and quantify endovascular coil distribution inside aneurysms based on serial histological images of experimental aneurysms. Seventeen histological images from 10 elastase-induced saccular aneurysms in rabbits treated with coils were studied. In-slice coil density, defined as the area taken up by coil winds, was calculated on each histological image. Images were analyzed by partitioning the aneurysm along its longitudinal and radial axes. Coil distribution was quantified by measuring and comparing the in-slice coil density of each partition. Mean total in-slice coil density was 22.0 ± 6.2% (range 10.1-30.2%). The density was non-significantly different (p = 0.465) along the longitudinal axis. A significant difference (p < 0.001) between peripheral and core densities was found. Additionally, the peripheral-core density ratio was observed to be inversely proportional to the total in-slice coil density (R(2)=0.57, p <0.001). This ratio was near unity for high in-slice coil density (around 30%). These findings demonstrate and confirm that coils tend to be located near the aneurysm periphery when few are inserted. However, when more coils are added, the radial distribution becomes more homogeneous. Coils are homogeneously distributed along the longitudinal axis.

Control of Post-disruption Runaway Electron Beams in the DIII-D Tokamak

NASA Astrophysics Data System (ADS)

Eidietis, N. W.

2011-10-01

Recent experiments on DIII-D have demonstrated real-time control of post-disruption runaway electron (RE) beams, presenting the possibility for slow, controlled dissipation of the beam energy. RE beams will present a greater challenge to ITER than present tokamaks due to ITER's high RE avalanche gain constant [Nucl.Fusion 37, 1355-62 (1997)] and the difficulty repairing potential damage to its first wall. In the rare event that disruption control and mitigation schemes fail to suppress RE generation, active control of the RE beam may be an important line of defense to prevent rapid, localized deposition of RE beam energy on the first wall. Initially, sustaining a RE beam plateau requires avoiding radial collapse of the beam into the inner wall during the first 1-2 wall penetration times following the current quench (CQ). This collapse is caused by attractive induced currents in the wall and a lack of radial equilibrium with slow vertical field coils. The collapse is avoided by slewing the inner PF coils to push the RE beam off the wall while reducing the outer PF coil currents. Beam survival through this phase requires sufficient RE plateau current (IRE) and power supply slew rates to re-establish equilibrium. Following that transient period, RE beam vertical position was dynamically controlled, and stabilization was maintained in an elongated (κ <= 1 . 8) DND configuration for up 250ms. Most controlled RE beams end in a rapid vertical displacement event (VDE), indicating that the profiles evolve even as the position is controlled. Experimental radial evolution and VDE onset are shown to be consistent with theoretical calculations of controllability boundaries. However, ohmic regulation of IRE has been shown to delay VDEs to the pre-programmed ramp-down time, indicating that steady-state control may be achievable. Supported by the US DOE under DE-FC02-04ER54698.

Arterial wall histology in chronic pulsatile-flow and continuous-flow device circulatory support.

PubMed

Potapov, Evgenij V; Dranishnikov, Nikolay; Morawietz, Lars; Stepanenko, Alexander; Rezai, Sajjad; Blechschmidt, Cristiane; Lehmkuhl, Hans B; Weng, Yuguo; Pasic, Miralem; Hübler, Michael; Hetzer, Roland; Krabatsch, Thomas

2012-11-01

Continuous-flow (CF) ventricular assist devices (VAD) are an established option for treatment of end-stage heart failure. However, the effect of long-term CF with lack of peripheral arterial wall motions on blood pressure regulation and end-organ arterial wall sclerosis, especially in the case of long-term support (> 3 years), remains unclear. Tissue samples obtained at autopsy from liver, kidney, coronary arteries, and brain from 27 VAD recipients supported for > 180 days between 2000 and 2010 were histologically examined to assess vascular alterations, including perivascular infiltrate, intravascular infiltrate, wall thickness, thrombosis, endothelial cell swelling, vessel wall necrosis, and peri-vascular fibrosis. Pulsatile-flow (PF) devices had been inserted in 9 patients and CF devices had been inserted in 16. The pathologist was blinded to the group distribution. Demographic, pharmacologic, and clinical data were retrospectively analyzed before surgery and during the follow-up period of up to 24 months. Median duration of support was 467 days (range, 235-1,588 days) in the PF group and 263 days (range, 182-942 days) in the CF group. Demographic and clinical data before and after surgery were similar. Amiodarone was more often used during follow-up in CF group than in the PF group (61% vs 10%, p = 0.009). Throughout the follow-up period, mean arterial pressure did not differ between recipients of the 2 pump types, nor did systolic and diastolic pressure, except at 2 weeks after VAD implantation, when systolic blood pressure was higher (p = 0.05) and diastolic lower (p = 0.03) in the PF group. Histologic studies did not identify any relevant differences in arterial wall characteristics between the 2 groups. Long-term mechanical circulatory support with CF devices does not adversely influence arterial wall properties of the end-organ vasculature. Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Characterizing permanent magnet blocks with Helmholtz coils

NASA Astrophysics Data System (ADS)

Carnegie, D. W.; Timpf, J.

1992-08-01

Most of the insertion devices to be installed at the Advanced Photon Source will utilize permanent magnets in their magnetic structures. The quality of the spectral output is sensitive to the errors in the field of the device which are related to variations in the magnetic properties of the individual blocks. The Advanced Photon Source will have a measurement facility to map the field in the completed insertion devices and equipment to test and modify the magnetic strength of the individual magnet blocks. One component of the facility, the Helmholtz coil permanent magnet block measurement system, has been assembled and tested. This system measures the total magnetic moment vector of a block with a precision better than 0.01% and a directional resolution of about 0.05°. The design and performance of the system will be presented.

Improvement of the radiographic method for measurement of effective energy of pulsed X-ray emission from a PF device for different anode's insert materials.

PubMed

Miremad, Seyed Milad; Shirani, Babak

2018-06-01

In this paper, effective energy of pulsed X-Ray emitted from a Mather-type plasma focus device in stored energy of 2.5 kJ with six different anode's insert materials was measured using radiographic method with attenuation filters. Since intensity and energy of X-ray beam were considerably changed with changing the insert material, the method was improved by using different filters simultaneously in all the experiments and selection of the best filter in each experiment according to the appropriate criteria. Effective energy of pulsed X-ray beam was measured 16, 28, 50, 51, 34 and 44 keV when aluminum, copper, zinc, tin, tungsten and lead were used as insert materials, and aluminum, copper, silver, silver, copper and lead were used as filters, respectively. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

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

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

Starter for inductively coupled plasma tube

DOEpatents

Hull, Donald E.; Bieniewski, Thomas M.

1988-01-01

A starter assembly is provided for use with an inductively coupled plasma (ICP) tube to reliably initate a plasma at internal pressures above about 30 microns. A conductive probe is inserted within the inductor coil about the tube and insulated from the tube shield assembly. A capacitive circuit is arranged for momentarily connecting a high voltage radio-frequency generator to the probe while simultaneously energizing the coil. When the plasma is initiated the probe is disconnected from the generator and electrically connected to the shield assembly for operation.

Method and apparatus for making superconductive magnet coils

DOEpatents

Borden, A.R.

1983-11-07

A curved, shell-type magnet coil, adapted to be used in a superconducting magnet, is wound by providing a mandrel having a tubular cylindrical mid-portion terminating at both ends in tapered end portions formed with longitudinal slots having flexible fingers therebetween. An elongated electrical conductor is wound around an elongated oval-shaped pole island engaged with the outside of the cylindrical mid-portion, to form a multiplicity of oval-shaped turns engaged with a 180-degree segment of the mandrel. The coil turns have longitudinal portions with curved portions therebetween, engaging the tapered end portions of the mandrel. Upon completion of the winding, tapered expansion members are fully inserted into the tapered end portions, to displace the flexible fingers outwardly into a cylindrical form and to displace the curved portions of the turns into a shape conforming to such cylindrical form while also exerting increased tension upon the turns to minimize draping of the turns and to enhance the mechanical integrity of the coil. A half cylinder clamp may then be employed to clamp the coil, whereupon the coil may be solidified by the use of an epoxy adhesive.

Method and apparatus for making superconductive magnet coils

DOEpatents

Borden, Albert R.

1985-01-01

A curved, shell-type magnet coil, adapted to be used in a superconducting magnet, is wound by providing a mandrel having a tubular cylindrical mid-portion terminating at both ends in tapered end portions formed with longitudinal slots having flexible fingers therebetween. An elongated electrical conductor is wound around an elongated oval-shaped pole island engaged with the outside of the cylindrical mid-portion, to form a multiplicity of oval-shaped turns engaged with a 180-degree segment of the mandrel. The coil turns have longitudinal portions with curved portions therebetween, engaging the tapered end portions of the mandrel. Upon completion of the winding, tapered expansion members are fully inserted into the tapered end portions, to displace the flexible fingers outwardly into a cylindrical form and to displace the curved portions of the turns into a shape conforming to such cylindrical form while also exerting increased tension upon the turns to minimize draping of the turns and to enhance the mechanical integrity of the coil. A half cylinder clamp may then be employed to clamp the coil, whereupon the coil may be solified by the use of an epoxy adhesive.

Development of a compact 30 T magnetic field system for OMEGA

NASA Astrophysics Data System (ADS)

Fiksel, G.; Backhus, R.; McNally, P.; Viges, E.; Villalta, M.; Jacobs-Perkins, D.; Betti, R.

2017-10-01

Aiming at conducting studies of magnetized high-energy density plasmas in a high magnetic field, we are developing a compact system capable of creating a pulsed magnetic field of about 30T in a volume of several cubic centimeters. The system prototype will be tested at the University of Michigan and will be adopted afterwards for use at the OMEGA facility of the Laboratory for Laser Energetics (LLE) of the University of Rochester, NY. The system consists of a pulsed power supply situated outside of the Omega vacuum chamber and a magnetic coil inserted into the chamber with a diagnostic inserter. The power supply is based on a 50 μF/20kV storage capacitor and is capable of driving a pulse of current of up to 50kA through the coil. The power supply is connected with the coil via a low-inductive chain of power cables and a strip transmission line. The system electrical, magnetic, and thermal analysis will be presented along with the results of initial testing. This work is supported in part through a DOE-OFES award DE-SC0016258 and a University of Michigan research Grant U051442.

Status of the Superconducting Insertion Device Control at TLS

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

Hu, K. H.; Wang, C. J.; Lee, Demi

2007-01-19

Superconducting insertion devices are installed at Taiwan Light Source to meet the rapidly growing demand of X-ray users. A control system supports the operation of all these superconducting insertion devices. Control system coordinates the operation of the main power supply and the trimming power supply to charge/discharge the magnet and provide essential interlock protection for the coils and vacuum ducts. Quench protection and various cryogenic interlocks are designed to prevent damage to the magnet. A friendly user interface supports routine operation. Various applications are also developed to aid the operation of these insertion devices. Design consideration and details of themore » implementation will be summarized in this report.« less

Improved Separations of Proteins and Sugar Derivatives Using the Small-Scale Cross-Axis Coil Planet Centrifuge with Locular Multilayer Coiled Columns

PubMed Central

Shinomiya, Kazufusa; Umezawa, Motoki; Seki, Manami; Nitta, Jun; Zaima, Kazumasa; Harikai, Naoki; Ito, Yoichiro

2016-01-01

1) Background Countercurrent chromatography (CCC) is liquid-liquid partition chromatography without using a solid support matrix. This technique requires further improvement of partition efficiency and shortening theseparation time. 2) Methods The locular multilayer coils modified with and without mixer glass beads were developed for the separation of proteins and 4-methylumbelliferyl (MU) sugar derivatives using the small-scale cross-axis coil planet centrifuge. 3) Results Proteins were well separated from each other and the separation was improved at a low flow rate of the mobile phase. On the other hand, 4-MU sugar derivatives were sufficiently resolved with short separation time at a highflow rate of the mobile phase under satisfactory stationary phase retention. 4) Conclusion Effective separations were achieved using the locular multilayer coil for proteins with aqueous-aqueous polymer phase systems and for 4-MU sugar derivatives with organic-aqueous two-phase solvent systems by inserting a glass bead into each locule. PMID:27891507

Gene leopard nuclei (len P103) participating in control of disjunction and coiling of chromosomes in Drosophila

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

Omel`yanchuk, L.V.

1995-12-01

A lethal insertion of an element P[lArB], which caused nondisjunction and structural abnormalities in chromosomes in the neuroblasts of homozygous larvae, was found. The insertion was mapped to region 57B1-12 of the polytene map of chromosome 2 of Drosophila. The expression of the corresponding gene was found in testes, ovaries, and neural ganglia. 8 refs., 6 figs.

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

Design optimization of superconducting coils based on asymmetrical characteristics of REBCO tapes

NASA Astrophysics Data System (ADS)

Hong, Zhiyong; Li, Wenrong; Chen, Yanjun; Gömöry, Fedor; Frolek, Lubomír; Zhang, Min; Sheng, Jie

2018-07-01

Angle dependence Ic(B,θ) of superconducting tape is a crucial parameter to calculate the influence of magnetic field during the design of superconducting applications,. This paper focuses on the asymmetrical characteristics found in REBCO tapes and further applications based on this phenomenon. This paper starts with angle dependence measurements of different HTS tapes, asymmetrical characteristics are found in some of the testing samples. On basis of this property, optimization of superconducting coils in superconducting motor, transformer and insert magnet is discussed by simulation. Simplified experiments which represent the structure of insert magnet were carried out to prove the validity of numerical studies. Conclusions obtained in this paper show that the asymmetrical property of superconducting tape is quite important in design of superconducting applications, and optimized winding technique based on this property can be used to improve the performance of superconducting devices.

An Evolutionarily Conserved Family of Virion Tail Needles Related to Bacteriophage P22 gp26: Correlation between Structural Stability and Length of the -Helical Trimeric Coiled Coil

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

Bhardwaj, A.; Walker-Kopp, N; Casjens, S

2009-01-01

Bacteriophages of the Podoviridae family use short noncontractile tails to inject their genetic material into Gram-negative bacteria. In phage P22, the tail contains a thin needle, encoded by the phage gene 26, which is essential both for stabilization and for ejection of the packaged viral genome. Bioinformatic analysis of the N-terminal domain of gp26 (residues 1-60) led us to identify a family of genes encoding putative homologues of the tail needle gp26. To validate this idea experimentally and to explore their diversity, we cloned the gp26-like gene from phages HK620, Sf6 and HS1, and characterized these gene products in solution.more » All gp26-like factors contain an elongated {alpha}-helical coiled-coil core consisting of repeating, adjacent trimerization heptads and form trimeric fibers with length ranging between about 240 to 300 {angstrom}. gp26 tail needles display a high level of structural stability in solution, with Tm (temperature of melting) between 85 and 95 C. To determine how the structural stability of these phage fibers correlates with the length of the {alpha}-helical core, we investigated the effect of insertions and deletions in the helical core. In the P22 tail needle, we identified an 85-residue-long helical domain, termed MiCRU (minimal coiled-coil repeat unit), that can be inserted in-frame inside the gp26 helical core, preserving the straight morphology of the fiber. Likewise, we were able to remove three quarters of the helical core of the HS1 tail needle, minimally decreasing the stability of the fiber. We conclude that in the gp26 family of tail needles, structural stability increases nonlinearly with the length of the {alpha}-helical core. Thus, the overall stability of these bacteriophage fibers is not solely dependent on the number of trimerization repeats in the {alpha}-helical core.« less

Wireless power delivery for retinal prostheses.

PubMed

Ng, David C; Williams, Chris E; Allen, Penny J; Bai, Shun; Boyd, Clive S; Meffin, Hamish; Halpern, Mark E; Skafidas, Efstratios

2011-01-01

Delivering power to an implanted device located deep inside the body is not trivial. This problem is made more challenging if the implanted device is in constant motion. This paper describes two methods of transferring power wirelessly by means of magnetic induction coupling. In the first method, a pair of transmit and receive coils is used for power transfer over a large distance (compared to their diameter). In the second method, an intermediate pair of coils is inserted in between transmit and receive coils. Comparison between the power transfer efficiency with and without the intermediate coils shows power transfer efficiency to be 11.5 % and 8.8 %, respectively. The latter method is especially suitable for powering implanted devices in the eye due to immunity to movements of the eye and ease of surgery. Using this method, we have demonstrated wireless power delivery into an animal eye.

Embolization with Tornado coils to control bleeding from an arterioureteral fistula.

PubMed

Jacobs, Bruce L; Maranchie, Jodi K

2007-12-01

Arterioureteral fistulae are rare, but potentially life-threatening causes of bleeding. We present a case of an 82 year-old woman with refractory, transfusion-dependent bleeding from an arterial fistula to her right ureteral stump, following right radical nephrectomy for advanced renal cell carcinoma. Cystoscopy with retrograde ureteral stump embolization using Tornado (Cook Medical, Bloomington, Indiana, USA) coils plus a slurry of thrombin-soaked Gelfoam (Pfizer Inc., New York, New York, USA) was performed, which led to prompt resolution of the patient's hematuria requiring no further hospitalizations or transfusions. Retrograde insertion of coils and injection of thrombin-soaked Gelfoam can be a minimally invasive, safe, and durable alternative for controlling hemorrhage from an arterioureteral fistula to a ureteral stump.

Is 3-methyl-2-oxazolidinone a suitable solvent for lithium-ion batteries?

NASA Astrophysics Data System (ADS)

Gzara, L.; Chagnes, A.; Carré, B.; Dhahbi, M.; Lemordant, D.

3-Methyl-2-oxazolidinone (MeOx) has been mixed to ethylene carbonate (EC) or dimethyl carbonate (DMC) in presence of lithium tetrafluoroborate (LiBF 4) or lithium hexafluorophosphate (LiPF 6) for use as electrolyte in lithium batteries. The optimized electrolytes in term of conductivity and viscosity are MeOx:EC, x(MeOx) = 0.5 and MeOx:DMC, x(MeOx) = 0.4 in presence of LiBF 4 (1 M) or LiPF 6 (1 M). MeOx:EC electrolytes have a better thermal stability than MeOx:DMC electrolytes but the low wettability of the Celgard separator by MeOx:EC prevents its use in lithium batteries. No lithium insertion-deinsertion occurs when LiPF 6 is used as salt in MeOx-based electrolytes. MeOx:DMC, x(MeOx) = 0.4 + LiBF 4 (1 M) exhibits a good cycling ability at a graphite electrode but all the investigated electrolytes containing MeOx have a low stability in oxidation at a lithium cobalt oxide electrode (Li xCoO 2).

Starter for inductively coupled plasma tube

DOEpatents

Hull, D.E.; Bieniewski, T.M.

1988-08-23

A starter assembly is provided for use with an inductively coupled plasma (ICP) tube to reliably initiate a plasma at internal pressures above about 30 microns. A conductive probe is inserted within the inductor coil about the tube and insulated from the tube shield assembly. A capacitive circuit is arranged for momentarily connecting a high voltage radio-frequency generator to the probe while simultaneously energizing the coil. When the plasma is initiated the probe is disconnected from the generator and electrically connected to the shield assembly for operation. 1 fig.

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

Skip residues modulate the structural properties of the myosin rod and guide thick filament assembly

DOE PAGES

Taylor, Keenan C.; Buvoli, Massimo; Korkmaz, Elif Nihal; ...

2015-07-06

The rod of sarcomeric myosins directs thick filament assembly and is characterized by the insertion of four skip residues that introduce discontinuities in the coiled-coil heptad repeats. We report in this paper that the regions surrounding the first three skip residues share high structural similarity despite their low sequence homology. Near each of these skip residues, the coiled-coil transitions to a nonclose-packed structure inducing local relaxation of the superhelical pitch. Moreover, molecular dynamics suggest that these distorted regions can assume different conformationally stable states. In contrast, the last skip residue region constitutes a true molecular hinge, providing C-terminal rod flexibility.more » Assembly of myosin with mutated skip residues in cardiomyocytes shows that the functional importance of each skip residue is associated with rod position and reveals the unique role of the molecular hinge in promoting myosin antiparallel packing. By defining the biophysical properties of the rod, the structures and molecular dynamic calculations presented here provide insight into thick filament formation, and highlight the structural differences occurring between the coiled-coils of myosin and the stereotypical tropomyosin. Finally, in addition to extending our knowledge into the conformational and biological properties of coiled-coil discontinuities, the molecular characterization of the four myosin skip residues also provides a guide to modeling the effects of rod mutations causing cardiac and skeletal myopathies.« less

The effect of scleral search coil lens wear on the eye.

PubMed

Murphy, P J; Duncan, A L; Glennie, A J; Knox, P C

2001-03-01

Scleral search coils are used to measure eye movements. A recent abstract suggests that the coil can affect the eye by decreasing visual acuity, increasing intraocular pressure, and damaging the corneal and conjunctival surface. Such findings, if repeated in all subjects, would cast doubt on the credibility of the search coil as a reliable investigative technique. The aim of this study was to reassess the effect of the scleral search coil on visual function. Six volunteer subjects were selected to undergo coil wear and baseline measurements were taken of logMAR visual acuity, non-contact tonometry, keratometry, and slit lamp examination. Four drops of 0.4% benoxinate hydrochloride were instilled before insertion of the lens by an experienced clinician. The lens then remained on the eye for 30 minutes. Measurements of the four ocular health parameters were repeated after 15 and 30 minutes of lens wear. The lens was then removed and the health of the eye reassessed. No obvious pattern of change was found in logMAR visual acuity, keratometry, or intraocular pressure. The lens did produce changes to the conjunctival and corneal surfaces, but this was not considered clinically significant. Search coils do not appear to cause any significant effects on visual function. However, thorough prescreening of subjects and post-wear checks should be carried out on all coil wearers to ensure no adverse effects have been caused.

Improving whole brain structural MRI at 4.7 Tesla using 4 irregularly shaped receiver coils.

PubMed

Carmichael, David W; Thomas, David L; De Vita, Enrico; Fernández-Seara, Maria A; Chhina, Navjeet; Cooper, Mark; Sunderland, Colin; Randell, Chris; Turner, Robert; Ordidge, Roger J

2006-09-01

Both higher magnetic field strengths (> or =3 T) and multiple receiver "array coils" can provide increased signal-to-noise ratio (SNR) for MRI. This increase in SNR can be used to obtain images with higher resolution, enabling better visualisation of structures within the human brain. However, high field strength systems also suffer from increased B(1) non-uniformity and increased power deposition, reaching specific absorption rate (SAR) limits more quickly. For these problems to be mitigated, a careful choice of both the pulse sequence design and transmit RF coil is required. This paper describes the use of a prototype array coil consisting of 4 irregularly shaped coils within a standard configuration for neuroimaging at 4.7 T (a head transmit/receive volume coil to minimise SAR and a head gradient insert for maximum gradient performance). With a fast spin echo (FSE) pulse sequence optimised for 4.7 T, this provides dramatically increased quality and resolution over a large brain volume. Using the array coil, a SNR improvement relative to the volume coil of 1-1.5 times in central brain areas and 2-3 times in cortical regions was obtained. Array coil images with a resolution of 352 x 352 x 2000 mum had a SNR of 16.0 to 26.2 in central regions and 19.9 to 34.8 in cortical areas. Such images easily demonstrate cortical myeloarchitecture, while still covering most of the brain in a approximately 12 min scan.

Simultaneous PET/MR imaging with a radio frequency-penetrable PET insert

PubMed Central

Grant, Alexander M.; Lee, Brian J.; Chang, Chen-Ming; Levin, Craig S.

2017-01-01

Purpose A brain sized radio-frequency (RF)-penetrable PET insert has been designed for simultaneous operation with MRI systems. This system takes advantage of electro-optical coupling and battery power to electrically float the PET insert relative to the MRI ground, permitting RF signals to be transmitted through small gaps between the modules that form the PET ring. This design facilitates the use of the built-in body coil for RF transmission, and thus could be inserted into any existing MR site wishing to achieve simultaneous PET/MR imaging. The PET detectors employ non-magnetic silicon photomultipliers in conjunction with a compressed sensing signal multiplexing scheme, and optical fibers to transmit analog PET detector signals out of the MRI room for decoding, processing, and image reconstruction. Methods The PET insert was first constructed and tested in a laboratory benchtop setting, where tomographic images of a custom resolution phantom were successfully acquired. The PET insert was then placed within a 3T body MRI system, and tomographic resolution/contrast phantom images were acquired both with only the B0 field present, and under continuous pulsing from different MR imaging sequences. Results The resulting PET images have comparable contrast-to-noise ratios (CNR) under all MR pulsing conditions: the maximum percent CNR relative difference for each rod type among all four PET images acquired in the MRI system has a mean of 14.0±7.7%. MR images were successfully acquired through the RF-penetrable PET shielding using only the built-in MR body coil, suggesting that simultaneous imaging is possible without significant mutual interference. Conclusions These results show promise for this technology as an alternative to costly integrated PET/MR scanners; a PET insert that is compatible with any existing clinical MRI system could greatly increase the availability, accessibility, and dissemination of PET/MR. PMID:28102949

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.

A strip-shield improves the efficiency of a solenoid coil in probes for high-field solid-state NMR of lossy biological samples.

PubMed

Wu, Chin H; Grant, Christopher V; Cook, Gabriel A; Park, Sang Ho; Opella, Stanley J

2009-09-01

A strip-shield inserted between a high inductance double-tuned solenoid coil and the glass tube containing the sample improves the efficiency of probes used for high-field solid-state NMR experiments on lossy aqueous samples of proteins and other biopolymers. A strip-shield is a coil liner consisting of thin copper strips layered on a PTFE (polytetrafluoroethylene) insulator. With lossy samples, the shift in tuning frequency is smaller, the reduction in Q, and RF-induced heating are all significantly reduced when the strip-shield is present. The performance of 800MHz (1)H/(15)N and (1)H/(13)C double-resonance probes is demonstrated on aqueous samples of membrane proteins in phospholipid bilayers.

Structure of bacteriophage T4 fibritin: a segmented coiled coil and the role of the C-terminal domain.

PubMed

Tao, Y; Strelkov, S V; Mesyanzhinov, V V; Rossmann, M G

1997-06-15

Oligomeric coiled-coil motifs are found in numerous protein structures; among them is fibritin, a structural protein of bacteriophage T4, which belongs to a class of chaperones that catalyze a specific phage-assembly process. Fibritin promotes the assembly of the long tail fibers and their subsequent attachment to the tail baseplate; it is also a sensing device that controls the retraction of the long tail fibers in adverse environments and, thus, prevents infection. The structure of fibritin had been predicted from sequence and biochemical analyses to be mainly a triple-helical coiled coil. The determination of its structure at atomic resolution was expected to give insights into the assembly process and biological function of fibritin, and the properties of modified coiled-coil structures in general. The three-dimensional structure of fibritin E, a deletion mutant of wild-type fibritin, was determined to 2.2 A resolution by X-ray crystallography. Three identical subunits of 119 amino acid residues form a trimeric parallel coiled-coil domain and a small globular C-terminal domain about a crystallographic threefold axis. The coiled-coil domain is divided into three segments that are separated by insertion loops. The C-terminal domain, which consists of 30 residues from each subunit, contains a beta-propeller-like structure with a hydrophobic interior. The residues within the C-terminal domain make extensive hydrophobic and some polar intersubunit interactions. This is consistent with the C-terminal domain being important for the correct assembly of fibritin, as shown earlier by mutational studies. Tight interactions between the C-terminal residues of adjacent subunits counteract the latent instability that is suggested by the structural properties of the coiled-coil segments. Trimerization is likely to begin with the formation of the C-terminal domain which subsequently initiates the assembly of the coiled coil. The interplay between the stabilizing effect of the C-terminal domain and the labile coiled-coil domain may be essential for the fibritin function and for the correct functioning of many other alpha-fibrous proteins.

J-tube technique for double-j stent insertion during laparoscopic upper urinary tract surgical procedures.

PubMed

Kim, Hyung Suk; Lee, Byung Ki; Jung, Jin-Woo; Lee, Jung Keun; Byun, Seok-Soo; Lee, Sang Eun; Jeong, Chang Wook

2014-11-01

Double-J stent insertion has been generally performed during laparoscopic upper urinary tract (UUT) surgical procedures to prevent transient urinary tract obstruction and postoperative flank pain from ureteral edema and blood clots. Several restrictive conditions that make this procedure difficult and time consuming, however, include the coiled distal ends of the flexible Double-J stent and the limited bending angle of the laparoscopic instruments. To overcome these limitations, we devised a Double-J stent insertion method using the new J-tube technique. Between July 2011 and May 2013, Double-J stents were inserted using the J-tube technique in 33 patients who underwent a laparoscopic UUT surgical procedure by a single surgeon. The mean stent placement time was 4.8±2.7 minutes, and there were no intraoperative complications. In conclusion, the J-tube technique is a safe and time-saving method for Double-J stent insertion during laparoscopic surgical procedures.

Wedge and spring assembly for securing coils in electromagnets and dynamoelectric machines

DOEpatents

Lindner, Melvin; Cottingham, James G.

1996-03-12

A wedge and spring assembly for use in electromagnets or dynamoelectric machines having a housing with an axis therethrough and a plurality of coils supported on salient poles that extend radially inward from the housing toward the housing axis to define a plurality of interpole spaces. The wedge and spring assembly includes a nonmagnetic retainer spring and a nonmagnetic wedge. The retainer spring is formed to fit into one of the interpole spaces, and has juxtaposed ends defining between them a slit extending in a direction generally parallel to the housing axis. The wedge for insertion into the slit provides an outwardly directed force on respective portions of the juxtaposed ends to expand the slit so that respective portions of the retainer spring engage areas of the coils adjacent thereto, thereby resiliently holding the coils against their respective salient poles. The retainer spring is generally triangular shaped to fit within the interpole space, and the wedge is generally T-shaped.

Wedge and spring assembly for securing coils in electromagnets and dynamoelectric machines

DOEpatents

Lindner, M.; Cottingham, J.G.

1996-03-12

A wedge and spring assembly for use in electromagnets or dynamoelectric machines is disclosed having a housing with an axis therethrough and a plurality of coils supported on salient poles that extend radially inward from the housing toward the housing axis to define a plurality of interpole spaces. The wedge and spring assembly includes a nonmagnetic retainer spring and a nonmagnetic wedge. The retainer spring is formed to fit into one of the interpole spaces, and has juxtaposed ends defining between them a slit extending in a direction generally parallel to the housing axis. The wedge for insertion into the slit provides an outwardly directed force on respective portions of the juxtaposed ends to expand the slit so that respective portions of the retainer spring engage areas of the coils adjacent thereto, thereby resiliently holding the coils against their respective salient poles. The retainer spring is generally triangular shaped to fit within the interpole space, and the wedge is generally T-shaped. 6 figs.

The effect of scleral search coil lens wear on the eye

PubMed Central

Murphy, P.; Duncan, A.; Glennie, A.; Knox, P.

2001-01-01

BACKGROUND/AIM—Scleral search coils are used to measure eye movements. A recent abstract suggests that the coil can affect the eye by decreasing visual acuity, increasing intraocular pressure, and damaging the corneal and conjunctival surface. Such findings, if repeated in all subjects, would cast doubt on the credibility of the search coil as a reliable investigative technique. The aim of this study was to reassess the effect of the scleral search coil on visual function.
METHODS—Six volunteer subjects were selected to undergo coil wear and baseline measurements were taken of logMAR visual acuity, non-contact tonometry, keratometry, and slit lamp examination. Four drops of 0.4% benoxinate hydrochloride were instilled before insertion of the lens by an experienced clinician. The lens then remained on the eye for 30 minutes. Measurements of the four ocular health parameters were repeated after 15 and 30 minutes of lens wear. The lens was then removed and the health of the eye reassessed.
RESULTS—No obvious pattern of change was found in logMAR visual acuity, keratometry, or intraocular pressure. The lens did produce changes to the conjunctival and corneal surfaces, but this was not considered clinically significant.
CONCLUSION—Search coils do not appear to cause any significant effects on visual function. However, thorough prescreening of subjects and post-wear checks should be carried out on all coil wearers to ensure no adverse effects have been caused.

 PMID:11222341

Structure of the WipA protein reveals a novel tyrosine protein phosphatase effector from Legionella pneumophila.

PubMed

Pinotsis, Nikos; Waksman, Gabriel

2017-06-02

Legionnaires' disease is a severe form of pneumonia caused by the bacterium Legionella pneumophila. L. pneumophila pathogenicity relies on secretion of more than 300 effector proteins by a type IVb secretion system. Among these Legionella effectors, WipA has been primarily studied because of its dependence on a chaperone complex, IcmSW, for translocation through the secretion system, but its role in pathogenicity has remained unknown. In this study, we present the crystal structure of a large fragment of WipA, WipA435. Surprisingly, this structure revealed a serine/threonine phosphatase fold that unexpectedly targets tyrosine-phosphorylated peptides. The structure also revealed a sequence insertion that folds into an α-helical hairpin, the tip of which adopts a canonical coiled-coil structure. The purified protein was a dimer whose dimer interface involves interactions between the coiled coil of one WipA molecule and the phosphatase domain of another. Given the ubiquity of protein-protein interaction mediated by interactions between coiled-coils, we hypothesize that WipA can thereby transition from a homodimeric state to a heterodimeric state in which the coiled-coil region of WipA is engaged in a protein-protein interaction with a tyrosine-phosphorylated host target. In conclusion, these findings help advance our understanding of the molecular mechanisms of an effector involved in Legionella virulence and may inform approaches to elucidate the function of other effectors. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

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.

Numerical investigations of MRI RF field induced heating for external fixation devices

PubMed Central

2013-01-01

Background The magnetic resonance imaging (MRI) radio frequency (RF) field induced heating on external fixation devices can be very high in the vicinity of device screws. Such induced RF heating is related to device constructs, device placements, as well as the device insertion depth into human subjects. In this study, computational modeling is performed to determine factors associated with such induced heating. Methods Numerical modeling, based on the finite-difference time-domain (FDTD) method, is used to evaluate the temperature rises near external device screw tips inside the ASTM phantom for both 1.5-T and 3-T MRI systems. The modeling approach consists of 1) the development of RF coils for 1.5-T and 3-T, 2) the electromagnetic simulations of energy deposition near the screw tips of external fixation devices, and 3) the thermal simulations of temperature rises near the tips of these devices. Results It is found that changing insertion depth and screw spacing could largely affect the heating of these devices. In 1.5-T MRI system, smaller insertion depth and larger pin spacing will lead to higher temperature rise. However, for 3-T MRI system, the relation is not very clear when insertion depth is larger than 5 cm or when pin spacing became larger than 20 cm. The effect of connection bar material on device heating is also studied and the heating mechanism of the device is analysed. Conclusions Numerical simulation is used to study RF heating for external fixation devices in both 1.5-T and 3-T MRI coils. Typically, shallower insertion depth and larger pin spacing with conductive bar lead to higher RF heating. The heating mechanism is explained using induced current along the device and power decay inside ASTM phantom. PMID:23394173

A Conformational Change of the γ Subunit Indirectly Regulates the Activity of Cyanobacterial F1-ATPase*

PubMed Central

Sunamura, Ei-Ichiro; Konno, Hiroki; Imashimizu, Mari; Mochimaru, Mari; Hisabori, Toru

2012-01-01

The central shaft of the catalytic core of ATP synthase, the γ subunit consists of a coiled-coil structure of N- and C-terminal α-helices, and a globular domain. The γ subunit of cyanobacterial and chloroplast ATP synthase has a unique 30–40-amino acid insertion within the globular domain. We recently prepared the insertion-removed α3β3γ complex of cyanobacterial ATP synthase (Sunamura, E., Konno, H., Imashimizu-Kobayashi, M., and Hisabori, T. (2010) Plant Cell Physiol. 51, 855–865). Although the insertion is thought to be located in the periphery of the complex and far from catalytic sites, the mutant complex shows a remarkable increase in ATP hydrolysis activity due to a reduced tendency to lapse into ADP inhibition. We postulated that removal of the insertion affects the activity via a conformational change of two central α-helices in γ. To examine this hypothesis, we prepared a mutant complex that can lock the relative position of two central α-helices to each other by way of a disulfide bond formation. The mutant obtained showed a significant change in ATP hydrolysis activity caused by this restriction. The highly active locked complex was insensitive to N-dimethyldodecylamine-N-oxide, suggesting that the complex is resistant to ADP inhibition. In addition, the lock affected ϵ inhibition. In contrast, the change in activity caused by removal of the γ insertion was independent from the conformational restriction of the central axis component. These results imply that the global conformational change of the γ subunit indirectly regulates complex activity by changing both ADP inhibition and ϵ inhibition. PMID:23012354

Experimental MRI-SPECT insert system with Hybrid Semiconductor detectors Timepix for MR animal scanner Bruker 47/20

NASA Astrophysics Data System (ADS)

Zajicek, J.; Burian, M.; Soukup, P.; Novak, V.; Macko, M.; Jakubek, J.

2017-01-01

Multimodal medical imaging based on Magnetic Resonance is mainly combinated with one of the scintigraphic method like PET or SPECT. These methods provide functional information whereas magnetic resonance imaging provides high spatial resolution of anatomical information or complementary functional information. Fusion of imaging modalities allows researchers to obtain complimentary information in a single measurement. The combination of MRI with SPECT is still relatively new and challenging in many ways. The main complication of using SPECT in MRI systems is the presence of a high magnetic field therefore (ferro)magnetic materials have to be eliminated. Furthermore the application of radiofrequency fields within the MR gantry does not allow for the use of conductive structures such as the common heavy metal collimators. This work presents design and construction of an experimental MRI-SPECT insert system and its initial tests. This unique insert system consists of an MR-compatible SPECT setup with CdTe pixelated sensors Timepix tungsten collimators and a radiofrequency coil. Measurements were performed on a gelatine and tissue phantom with an embedded radioisotopic source (57Co 122 keV γ ray) inside the RF coil by the Bruker BioSpec 47/20 (4.7 T) MR animal scanner. The project was performed in the framework of the Medipix Collaboration.

A Field-Shaking System to Reduce the Screening Current-Induced Field in the 800-MHz HTS Insert of the MIT 1.3-GHz LTS/HTS NMR Magnet: A Small-Model Study.

PubMed

Lee, Jiho; Park, Dongkeun; Michael, Philip C; Noguchi, So; Bascuñán, Juan; Iwasa, Yukikazu

2018-04-01

In this paper, we present experimental results, of a small-model study, from which we plan to develop and apply a full-scale field-shaking system to reduce the screening current-induced field (SCF) in the 800-MHz HTS Insert (H800) of the MIT 1.3-GHz LTS/HTS NMR magnet (1.3G) currently under construction-the H800 is composed of 3 nested coils, each a stack of no-insulation (NI) REBCO double-pancakes. In 1.3G, H800 is the chief source of a large error field generated by its own SCF. To study the effectiveness of the field-shaking technique, we used two NI REBCO double-pancakes, one from Coil 2 (HCoil2) and one from Coil 3 (HCoil3) of the 3 H800 coils, and placed them in the bore of a 5-T/300-mm room-temperature bore low-temperature superconducting (LTS) background magnet. The background magnet is used not only to induce the SCF in the double-pancakes but also to reduce it by the field-shaking technique. For each run, we induced the SCF in the double-pancakes at an axial location where the external radial field Br > 0, then for the field-shaking, moved them to another location where the external axial field Bz ≫ B R . Due to the geometry of H800 and L500, top double-pancakes of 3 H800 coils will experience the considerable radial magnetic field perpendicular to the REBCO tape surface. To examine the effect of the field-shaking on the SCF, we tested each NI REBCO DP in the absence or presence of a radial field. In this paper, we report 77-K experimental results and analysis of the effect and a few significant remarks of the field-shaking.

Design and construction of a novel 1H/19F double-tuned coil system using PIN-diode switches at 9.4T.

PubMed

Choi, Chang-Hoon; Hong, Suk-Min; Ha, YongHyun; Shah, N Jon

2017-06-01

A double-tuned 1 H/ 19 F coil using PIN-diode switches was developed and its performance evaluated. The is a key difference from the previous developments being that this design used a PIN-diode switch in series with an additionally inserted inductor in parallel to one of the capacitors on the loop. The probe was adjusted to 19 F when the reverse bias voltage was applied (PIN-diode OFF), whilst it was switched to 1 H when forward current was flowing (PIN-diode ON). S-parameters and Q-factors of single- and double-tuned coils were examined and compared with/without a phantom on the bench. Imaging experiments were carried out on a 9.4T preclinical scanner. All coils were tuned at resonance frequencies and matched well. It is shown that the Q-ratio and SNR of double-tuned coil at 19 F frequency are nearly as good as those of a single-tuned coil. Since the operating frequency was tuned to 19 F when the PIN-diodes were turned off, losses due to PIN-diodes were substantially lower resulting in the provision of excellent image quality of X-nuclei. Copyright © 2017 Elsevier Inc. All rights reserved.

Eddy current inspection tool which is selectively operable in a discontinuity detection mode and a discontinuity magnitude mode

DOEpatents

Petrini, Richard R.; Van Lue, Dorin F.

1983-01-01

A miniaturized inspection tool, for testing and inspection of metal objects in locations with difficult accessibility, which comprises eddy current sensing equipment (12) with a probe coil (11), and associated coaxial coil cable (13), coil energizing means (21), and circuit means (21, 12) responsive to impedance changes in the coil as effected by induced eddy currents in a test object to produce a data output signal proportional to such changes. The coil and cable are slideably received in the utility channel of the flexible insertion tube 17 of fiberoptic scope 10. The scope 10 is provided with light transmitting and receiving fiberoptics for viewing through the flexible tube, and articulation means (19, 20) for articulating the distal end of the tube and permitting close control of coil placement relative to a test object. The eddy current sensing equipment includes a tone generator 30 for generating audibly signals responsive to the data output signal. In one selected mode of operation, the tone generator responsive to the output signal above a selected level generates a constant single frequency tone for signalling detection of a discontinuity and, in a second selected mode, generates a tone whose frequency is proportional to the difference between the output signal and a predetermined selected threshold level.

Eddy current inspection tool which is selectively operable in a discontinuity detection mode and a discontinuity magnitude mode

DOEpatents

Petrini, R.R.; Van Lue, D.F.

1983-10-25

A miniaturized inspection tool, for testing and inspection of metal objects in locations with difficult accessibility, which comprises eddy current sensing equipment with a probe coil, and associated coaxial coil cable, coil energizing means, and circuit means responsive to impedance changes in the coil as effected by induced eddy currents in a test object to produce a data output signal proportional to such changes. The coil and cable are slideably received in the utility channel of the flexible insertion tube of fiberoptic scope. The scope is provided with light transmitting and receiving fiberoptics for viewing through the flexible tube, and articulation means for articulating the distal end of the tube and permitting close control of coil placement relative to a test object. The eddy current sensing equipment includes a tone generator 30 for generating audibly signals responsive to the data output signal. In one selected mode of operation, the tone generator responsive to the output signal above a selected level generates a constant single frequency tone for signaling detection of a discontinuity and, in a second selected mode, generates a tone whose frequency is proportional to the difference between the output signal and a predetermined selected threshold level. 5 figs.

30 CFR 7.304 - Technical requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... (coarse, loose fitting) threads. The covers shall be secured against loosening. (5) Flat surfaces between... flame-arresting path shall be finished during the manufacturing process to not more than 250 microinches... requirements as the pole piece. (12) Coil-thread inserts, if used in holes for fastenings, shall meet the...

30 CFR 7.304 - Technical requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... (coarse, loose fitting) threads. The covers shall be secured against loosening. (5) Flat surfaces between... flame-arresting path shall be finished during the manufacturing process to not more than 250 microinches... requirements as the pole piece. (12) Coil-thread inserts, if used in holes for fastenings, shall meet the...

30 CFR 7.304 - Technical requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (coarse, loose fitting) threads. The covers shall be secured against loosening. (5) Flat surfaces between... flame-arresting path shall be finished during the manufacturing process to not more than 250 microinches... requirements as the pole piece. (12) Coil-thread inserts, if used in holes for fastenings, shall meet the...

30 CFR 7.304 - Technical requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (coarse, loose fitting) threads. The covers shall be secured against loosening. (5) Flat surfaces between... flame-arresting path shall be finished during the manufacturing process to not more than 250 microinches... requirements as the pole piece. (12) Coil-thread inserts, if used in holes for fastenings, shall meet the...

30 CFR 7.304 - Technical requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... (coarse, loose fitting) threads. The covers shall be secured against loosening. (5) Flat surfaces between... flame-arresting path shall be finished during the manufacturing process to not more than 250 microinches... requirements as the pole piece. (12) Coil-thread inserts, if used in holes for fastenings, shall meet the...

A mutant (‘lab strain’) of the hyperthermophilic archaeon Pyrococcus furiosus, lacking flagella, has unusual growth physiology

DOE PAGES

Lewis, Derrick L.; Notey, Jaspreet S.; Chandrayan, Sanjeev K.; ...

2014-12-04

In this paper, a mutant (‘lab strain’) of the hyperthermophilic archaeon Pyrococcus furiosus DSM3638 exhibited an extended exponential phase and atypical cell aggregation behavior. Genomic DNA from the mutant culture was sequenced and compared to wild-type (WT) DSM3638, revealing 145 genes with one or more insertions, deletions, or substitutions (12 silent, 33 amino acid substitutions, and 100 frame shifts). Approximately, half of the mutated genes were transposases or hypothetical proteins. The WT transcriptome revealed numerous changes in amino acid and pyrimidine biosynthesis pathways coincidental with growth phase transitions, unlike the mutant whose transcriptome reflected the observed prolonged exponential phase. Targetedmore » gene deletions, based on frame-shifted ORFs in the mutant genome, in a genetically tractable strain of P. furiosus (COM1) could not generate the extended exponential phase behavior observed for the mutant. For example, a putative radical SAM family protein (PF2064) was the most highly up-regulated ORF (>25-fold) in the WT between exponential and stationary phase, although this ORF was unresponsive in the mutant; deletion of this gene in P. furiosus COM1 resulted in no apparent phenotype. On the other hand, frame-shifting mutations in the mutant genome negatively impacted transcription of a flagellar biosynthesis operon (PF0329-PF0338).Consequently, cells in the mutant culture lacked flagella and, unlike the WT, showed minimal evidence of exopolysaccharide-based cell aggregation in post-exponential phase. Finally, electron microscopy of PF0331-PF0337 deletions in P. furiosus COM1 showed that absence of flagella impacted normal cell aggregation behavior and, furthermore, indicated that flagella play a key role, beyond motility, in the growth physiology of P. furiosus.« less

A mutant (‘lab strain’) of the hyperthermophilic archaeon Pyrococcus furiosus, lacking flagella, has unusual growth physiology

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

Lewis, Derrick L.; Notey, Jaspreet S.; Chandrayan, Sanjeev K.

In this paper, a mutant (‘lab strain’) of the hyperthermophilic archaeon Pyrococcus furiosus DSM3638 exhibited an extended exponential phase and atypical cell aggregation behavior. Genomic DNA from the mutant culture was sequenced and compared to wild-type (WT) DSM3638, revealing 145 genes with one or more insertions, deletions, or substitutions (12 silent, 33 amino acid substitutions, and 100 frame shifts). Approximately, half of the mutated genes were transposases or hypothetical proteins. The WT transcriptome revealed numerous changes in amino acid and pyrimidine biosynthesis pathways coincidental with growth phase transitions, unlike the mutant whose transcriptome reflected the observed prolonged exponential phase. Targetedmore » gene deletions, based on frame-shifted ORFs in the mutant genome, in a genetically tractable strain of P. furiosus (COM1) could not generate the extended exponential phase behavior observed for the mutant. For example, a putative radical SAM family protein (PF2064) was the most highly up-regulated ORF (>25-fold) in the WT between exponential and stationary phase, although this ORF was unresponsive in the mutant; deletion of this gene in P. furiosus COM1 resulted in no apparent phenotype. On the other hand, frame-shifting mutations in the mutant genome negatively impacted transcription of a flagellar biosynthesis operon (PF0329-PF0338).Consequently, cells in the mutant culture lacked flagella and, unlike the WT, showed minimal evidence of exopolysaccharide-based cell aggregation in post-exponential phase. Finally, electron microscopy of PF0331-PF0337 deletions in P. furiosus COM1 showed that absence of flagella impacted normal cell aggregation behavior and, furthermore, indicated that flagella play a key role, beyond motility, in the growth physiology of P. furiosus.« less

Developmental regulation of vascular endothelial growth/permeability factor messenger ribonucleic acid levels in and vascularization of the villous placenta during baboon pregnancy.

PubMed

Hildebrandt, V A; Babischkin, J S; Koos, R D; Pepe, G J; Albrecht, E D

2001-05-01

Vascular endothelial growth/permeability factor (VEG/PF) has an important role in angiogenesis; however, very little is known about the developmental regulation of VEG/PF and the vascular system within the placenta during human pregnancy. In the present study, therefore, a developmental approach was used in the baboon to determine the placental source of VEG/PF and its fms-like tyrosine kinase (flt-1) and kinase-insert domain containing (KDR/flk-1) receptors, and whether the rise in estrogen with advancing pregnancy was associated with a corresponding increase in placental VEG/PF expression and vascularization. VEG/PF messenger RNA (mRNA) levels were determined by competitive RT-PCR in villous cell fractions isolated by Percoll gradient centrifugation from placentas obtained on days 45 and 54 (very early), 60 (early), 100 (mid), and 165-170 (late) of baboon pregnancy (term = 184 days). Maternal peripheral serum estradiol increased from very low concentrations early in gestation (0.15-0.20 ng/ml) to an early surge of over 2.5 ng/ml on days 60-85, and peak levels of 4-6 ng/ml late in baboon pregnancy. VEG/PF mRNA was expressed in low level in the syncytiotrophoblast (<2,000 attomol/microgram total RNA), and values in this fraction did not change significantly with advancing gestation. VEG/PF mRNA expression was slightly greater in the inner villous core cell fraction; however, levels decreased (P < 0.05) between early and late gestation. Cytotrophoblasts were a major source of VEG/PF mRNA and levels increased (P < 0.01) from 3,631 +/- 844 attomol/microgram total RNA on day 45 to 25,807 +/- 5,873 attomol/microgram total RNA on day 170. VEG/PF protein expression determined by immunocytochemistry was abundant in cytotrophoblasts and lower in the syncytiotrophoblast and inner villous core cells. The flt-1 and KDR/flk-1 receptors were expressed in the vascular endothelial cells of the baboon villous placenta. The percentage of villous placenta occupied by blood vessels and the number of vessels/mm(2) villous tissue, determined by image analysis, progressively increased (P < 0.001; r = 0.97) from 3.4 +/- 0.2% and 447 +/- 29, respectively, on day 54 to 15.9 +/- 0.9% and 1,375 +/- 71, respectively, on day 170. In summary, the present study shows that villous cytotrophoblasts were a major source of VEG/PF mRNA and protein in the baboon villous placenta, and that cytotrophoblast VEG/PF mRNA levels and vascularization of the villous placenta closely paralleled the increase in estradiol concentrations of advancing pregnancy. These results are consistent with the concept that estrogen has an important role in establishing the new vascular system within the developing placenta during primate pregnancy and that VEG/PF mediates this process.

A Superconducting Switch for Insertion Devices with Variable Period Length

NASA Astrophysics Data System (ADS)

Holubek, T.; Baumbach, T.; Casalbuoni, S.; Gerstl, S.; Grau, A.; Hagelstein, M.; Jauregui, D. Saez de; Boffo, C.; Walter, W.

Superconducting insertion devices (IDs) are very attractive for synchrotron light sources since they offer the possibility to enhance the tuning range and functionality significantly by period length switching. Period length switching can be realized by reversing the current in a separately powered subset of the superconducting windings.So far, the first demonstration mock-up coil allowing period length tripling was fabricated and tested successfully. Here, we report on the feasibility of superconducting switches built to operate in a liquid helium bath and under conduction cooled conditions.

Development of an engineering model for ferromagnetic shape memory alloys

NASA Astrophysics Data System (ADS)

Tani, Yoshiaki; Todaka, Takashi; Enokizono, Masato

This paper presents a relationship among stress, temperature and magnetic properties of a ferromagnetic shape memory alloy. In order to derive an engineering model of ferromagnetic shape memory alloys, we have developed a measuring system of the relationship among stress, temperature and magnetic properties. The samples used in this measurement are Fe68-Ni10-Cr9-Mn7-Si6 wt% ferromagnetic shape memory alloy. They are thin ribbons made by rapid cooling in air. In the measurement, the ribbon sample is inserted into a sample holder winding consisting of the B-coil and compensation coils, and magnetized in an open solenoid coil. The ribbon is stressed with attachment weights and heated with a heating wire. The specific susceptibility was increased by applying tension, and slightly increased by heating below the Curie temperature.

Eddy current inspection tool. [Patent application

DOEpatents

Petrini, R.R.; Van Lue, D.F.

1980-10-29

A miniaturized inspection tool, for testing and inspection of metal objects in locations with difficult accessibility, which comprises eddy current sensing equipment with a probe coil, and associated coaxial coil cable, oil energizing means, and circuit means responsive to impedance changes in the coil as effected by induced eddy currents in a test object to produce a data output signal proportional to such changes. The coil and cable are slideably received in the utility channel of the flexible insertion tube of a fiberoptic scope. The scope is provided with light transmitting and receiving fiberoptics for viewing through the flexible tube, and articulation means for articulating the distal end of the tube and permitting close control of coil placement relative to a test object. The eddy current sensing equipment includes a tone generator for generating audible signals responsive to the data output signal. In one selected mode of operation, the tone generator responsive to the output signal above a selected level generates a constant single frequency tone for signalling detection of a discontinuity and, in a second selected mode, generates a tone whose frequency is proportional to the difference between the output signal and a predetermined selected threshold level.

30 CFR 18.32 - Fastenings-additional requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... preclude improper assembly. (d) Holes for fastenings shall not penetrate to the interior of an explosion...-inch of stock shall be left at the center of the bottom of each hole drilled for fastenings. (f...-tensile strength fastening(s) specified by the applicant. (i) Coil-thread inserts, if used in holes for...

30 CFR 18.32 - Fastenings-additional requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... preclude improper assembly. (d) Holes for fastenings shall not penetrate to the interior of an explosion...-inch of stock shall be left at the center of the bottom of each hole drilled for fastenings. (f...-tensile strength fastening(s) specified by the applicant. (i) Coil-thread inserts, if used in holes for...

30 CFR 18.32 - Fastenings-additional requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... preclude improper assembly. (d) Holes for fastenings shall not penetrate to the interior of an explosion...-inch of stock shall be left at the center of the bottom of each hole drilled for fastenings. (f...-tensile strength fastening(s) specified by the applicant. (i) Coil-thread inserts, if used in holes for...

30 CFR 18.32 - Fastenings-additional requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... preclude improper assembly. (d) Holes for fastenings shall not penetrate to the interior of an explosion...-inch of stock shall be left at the center of the bottom of each hole drilled for fastenings. (f...-tensile strength fastening(s) specified by the applicant. (i) Coil-thread inserts, if used in holes for...

Energetics of Na + Transport through the Electrode/Cathode Interface in Single Solvent Electrolytes

DOE PAGES

Browning, Katie L.; Sacci, Robert L.; Veith, Gabriel M.

2017-01-27

Here, the activation energy of desolvation for Na-ion electrolyte systems were studied using temperature dependent electrochemical impedance spectroscopy (EIS). Propylene carbonate (PC) and tetraglyme were chosen as solvents in single solvent electrolyte solution coupled with NaClO 4, NaPF 6, NaAsF 6, NaBF 4, and NaOFt salts. The results demonstrate the insertion and desolvation processes are extremely fast at or above room temperature. The data shows under optimal salt chemistry the desolvation activation energy is less than 21 kJ/mole. This is in contrast to the ~50 kJ/mole measured for analogous Li systems. The dominant factor affecting performance was the anion. Indeed,more » anions with lower donor numbers (PF 6 –, AsF 6 –) had more than 30 kJ/mole lower desolvation energies than species like NaBF 4 and NaOFt.« less

PF-AR NW14, a new time-resolved diffraction/scattering beamline

NASA Astrophysics Data System (ADS)

Nozawa, Shunsuke; Adachi, Shin-ichi; Tazaki, Ryoko; Takahashi, Jun-ichi; Itatani, Jiro; Daimon, Masahiro; Mori, Takeharu; Sawa, Hiroshi; Kawata, Hiroshi; Koshihara, Shin-ya

2005-01-01

NW14 is a new insertion device beamline at the Photon Factory Advanced Ring (PF-AR), which is a unique ring with full-time single-bunched operation, aiming for timeresolved x-ray diffraction/scattering and XAFS experiments. The primary scientific goal of this beamline is to observe the ultrafast dynamics of condensed matter systems such as organic and inorganic crystals, biological systems and liquids triggered by optical pulses. With the large photon fluxes derived from the undulator, it should become possible to take a snapshoot an atomic-scale image of the electron density distribution. By combining a series of images it is possible to produce a movie of the photo-induced dynamics with 50-ps resolution. The construction of the beamline is being funded by the ERATO Koshihara Non-equilibrium Dynamics Project of the Japan Science and Technology Agency (JST), and the beamline will be operational from autumn 2005.

Practical design of a 4 Tesla double-tuned RF surface coil for interleaved 1H and 23Na MRI of rat brain.

PubMed

Alecci, M; Romanzetti, S; Kaffanke, J; Celik, A; Wegener, H P; Shah, N J

2006-08-01

MRI is proving to be a very useful tool for sodium quantification in animal models of stroke, ischemia, and cancer. In this work, we present the practical design of a dual-frequency RF surface coil that provides (1)H and (23)Na images of the rat head at 4 T. The dual-frequency RF surface coil comprised of a large loop tuned to the (1)H frequency and a smaller co-planar loop tuned to the (23)Na frequency. The mutual coupling between the two loops was eliminated by the use of a trap circuit inserted in the smaller coil. This independent-loop design was versatile since it enabled a separate optimisation of the sensitivity and RF field distributions of the two coils. To allow for an easy extension of this simple double-tuned coil design to other frequencies (nuclei) and dimensions, we describe in detail the practical aspects of the workbench design and MRI testing using a phantom that mimics in vivo conditions. A comparison between our independent-loop, double-tuned coil and a single-tuned (23)Na coil of equal size obtained with a phantom matching in vivo conditions, showed a reduction of the (23)Na sensitivity (about 28 %) because of signal losses in the trap inductance. Typical congruent (1)H and (23)Na rat brain images showing good SNR ((23)Na: brain 7, ventricular cerebrospinal fluid 11) and spatial resolution ((23)Na: 1.25 x 1.25 x 5mm(3)) are also reported. The in vivo SNR values obtained with this coil were comparable to, if not better than, other contemporary designs in the literature.

Practical design of a 4 Tesla double-tuned RF surface coil for interleaved 1H and 23Na MRI of rat brain

NASA Astrophysics Data System (ADS)

Alecci, M.; Romanzetti, S.; Kaffanke, J.; Celik, A.; Wegener, H. P.; Shah, N. J.

2006-08-01

MRI is proving to be a very useful tool for sodium quantification in animal models of stroke, ischemia, and cancer. In this work, we present the practical design of a dual-frequency RF surface coil that provides 1H and 23Na images of the rat head at 4 T. The dual-frequency RF surface coil comprised of a large loop tuned to the 1H frequency and a smaller co-planar loop tuned to the 23Na frequency. The mutual coupling between the two loops was eliminated by the use of a trap circuit inserted in the smaller coil. This independent-loop design was versatile since it enabled a separate optimisation of the sensitivity and RF field distributions of the two coils. To allow for an easy extension of this simple double-tuned coil design to other frequencies (nuclei) and dimensions, we describe in detail the practical aspects of the workbench design and MRI testing using a phantom that mimics in vivo conditions. A comparison between our independent-loop, double-tuned coil and a single-tuned 23Na coil of equal size obtained with a phantom matching in vivo conditions, showed a reduction of the 23Na sensitivity (about 28 %) because of signal losses in the trap inductance. Typical congruent 1H and 23Na rat brain images showing good SNR ( 23Na: brain 7, ventricular cerebrospinal fluid 11) and spatial resolution ( 23Na: 1.25 × 1.25 × 5 mm 3) are also reported. The in vivo SNR values obtained with this coil were comparable to, if not better than, other contemporary designs in the literature.

Effect of gender, age and anthropometric variables on plantar fascia thickness at different locations in asymptomatic subjects.

PubMed

Pascual Huerta, Javier; Alarcón García, Juan María

2007-06-01

The study was aimed to investigate plantar fascia thickness at different locations in healthy asymptomatic subjects and its relationship to the following variables: weight, height, sex and age. The study evaluates 96 feet of healthy asymptomatic volunteers. The plantar fascia thickness was measured at four different locations: 1cm proximal to the insertion of the plantar fascia, at the insertion of the plantar fascia on the calcaneus and separate out 1 cm + 2 cm distal to the insertion. A 10 MHz linear-array transducer was used. There were statistically significant differences in plantar fascia thickness at the four different locations (p<0.001) although no differences in PF thickness were found between the two distal from insertion locations (1 and 2 cm). Multiple regression analysis showed sex as independent predictor of plantar fascia thickness at 1cm proximal to the insertion. At origin and 1cm distal to insertion weight was an independent predictor of plantar fascia thickness. There are differences of thickness at different locations of plantar fascia measured by ultrasonography. Thickness at 1cm proximal to the insertion is influenced by sex and thickness at origin and at 1cm distal to the insertion has a direct relationship with body weight. This could be attributed to the overloading effect that weight has on plantar fascia in healthy symptomatic subjects at these two locations. Height and age did not seem to influence as independent variables in plantar fascia thickness among non-painful subjects.

On the accurate analysis of vibroacoustics in head insert gradient coils.

PubMed

Winkler, Simone A; Alejski, Andrew; Wade, Trevor; McKenzie, Charles A; Rutt, Brian K

2017-10-01

To accurately analyze vibroacoustics in MR head gradient coils. A detailed theoretical model for gradient coil vibroacoustics, including the first description and modeling of Lorentz damping, is introduced and implemented in a multiphysics software package. Numerical finite-element method simulations were used to establish a highly accurate vibroacoustic model in head gradient coils in detail, including the newly introduced Lorentz damping effect. Vibroacoustic coupling was examined through an additional modal analysis. Thorough experimental studies were used to validate simulations. Average experimental sound pressure levels (SPLs) and accelerations over the 0-3000 Hz frequency range were 97.6 dB, 98.7 dB, and 95.4 dB, as well as 20.6 g, 8.7 g, and 15.6 g for the X-, Y-, and Z-gradients, respectively. A reasonable agreement between simulations and measurements was achieved. Vibroacoustic coupling showed a coupled resonance at 2300 Hz for the Z-gradient that is responsible for a sharp peak and the highest SPL value in the acoustic spectrum. We have developed and used more realistic multiphysics simulation methods to gain novel insights into the underlying concepts for vibroacoustics in head gradient coils, which will permit improved analyses of existing gradient coils and novel SPL reduction strategies for future gradient coil designs. Magn Reson Med 78:1635-1645, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Development and implementation of an 84-channel matrix gradient coil.

PubMed

Littin, Sebastian; Jia, Feng; Layton, Kelvin J; Kroboth, Stefan; Yu, Huijun; Hennig, Jürgen; Zaitsev, Maxim

2018-02-01

Design, implement, integrate, and characterize a customized coil system that allows for generating spatial encoding magnetic fields (SEMs) in a highly-flexible fashion. A gradient coil with a high number of individual elements was designed. Dimensions of the coil were chosen to mimic a whole-body gradient system, scaled down to a head insert. Mechanical shape and wire layout of each element were optimized to increase the local gradient strength while minimizing eddy current effects and simultaneously considering manufacturing constraints. Resulting wire layout and mechanical design is presented. A prototype matrix gradient coil with 12 × 7 = 84 elements consisting of two element types was realized and characterized. Measured eddy currents are <1% of the original field. The coil is shown to be capable of creating nonlinear, and linear SEMs. In a DSV of 0.22 m gradient strengths between 24 mT∕m and 78 mT∕m could be realized locally with maximum currents of 150 A. Initial proof-of-concept imaging experiments using linear and nonlinear encoding fields are demonstrated. A shielded matrix gradient coil setup capable of generating encoding fields in a highly-flexible manner was designed and implemented. The presented setup is expected to serve as a basis for validating novel imaging techniques that rely on nonlinear spatial encoding fields. Magn Reson Med 79:1181-1191, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Successful embolization using interlocking detachable coils for a congenital extrahepatic portosystemic venous shunt in a child.

PubMed

Yamagami, Takuji; Yoshimatsu, Rika; Matsumoto, Tomohiro; Terayama, Koshi; Nishiumra, Akira; Maeda, Yousuke; Nishimura, Tsunehiko

2007-11-01

The authors report the case of a 6-year-old boy with a congenital extrahepatic portosystemic venous shunt. He had hyperammonemia. The shunt was 18 mm in diameter and located between the inferior mesenteric vein and the left internal iliac vein. The flow in the shunt was very rapid. After decreasing blood flow by inflating a balloon catheter inserted into the left internal iliac vein from the femoral vein, a microcatheter was coaxially advanced to the shunt to embolize the shunt. Embolization was successfully performed with interlocking detachable coils and microcoils without any complication. This patient's hyperammonemia resolved soon after the procedure.

Carbon-based torsional and tensile artificial muscles driven by thermal expansion (presentation video)

NASA Astrophysics Data System (ADS)

Haines, Carter S.; Lima, Márcio D.; Li, Na; Spinks, Geoffrey M.; Foroughi, Javad; Madden, John D. W.; Kim, Shi-Hyeong; Fang, Shaoli; Jung de Andrade, Monica; Göktepe, Fatma; Göktepe, Ozer; Mirvakili, Seyed M.; Naficy, Sina; Lepró, Xavier; Oh, Jiyoung; Kozlov, Mikhail E.; Kim, Seon Jeong; Xu, Xiuru; Swedlove, Benjamin J.; Wallace, Gordon G.; Baughman, Ray H.

2014-03-01

High-performance artificial muscles have been produced from fibers having highly anisotropic thermal expansion. Inserting twist into these precursor fibers enables thermally-driven torsional actuation and can cause the formation of helical coils. Such coiled structures provide giant-stroke tensile actuation exceeding the 20% in-vivo contraction of natural muscles. This contraction is highly reversible, with over one million cycles demonstrated, and can occur without the hysteresis that plagues competing shape-memory and piezoelectric muscles. Several materials and composites are investigated, including low-cost, commercially-available muscle precursors, potentially facilitating thermally-responsive textiles that change porosity to provide wearer comfort.

Ion-solvation structure and battery electrode characteristics of nonflammable organic electrolytes based on tris(trifluoroethyl)phosphate dissolving lithium salts.

PubMed

Todorov, Yanko Marinov; Fujii, Kenta; Yoshimoto, Nobuko; Hirayama, Daisuke; Aoki, Masahiro; Mimura, Hideyuki; Morita, Masayuki

2017-11-29

The structure and properties of lithium salt solutions based on tris(2,2,2-trifluoroethyl)phosphate (TFEP) solvent have been studied to design a safer electrolyte system for large-sized lithium-ion battery applications. Influences of the ionic structure on the polarization behavior of the LiCoO 2 (LCO) positive electrode were investigated. The ionic conductivity and viscosity of the solution consisting of lithium salts dissolved in TFEP, LiX/TFEP (X = PF 6 , BF 4 and TFSA) (TFSA = (CF 3 SO 2 ) 2 N), were measured. The results suggest that the ion-solvation structure greatly depends on the anionic species in the salt. Spectroscopic measurements also support the conclusion that the Li + -solvation structure varies with the lithium salts. The differences in the ionic structure of LiX/TFEP influence the electrochemical oxidation potential of the solution and the polarization behavior of the LCO electrode. The overvoltage for Li-desertion/insertion from/into LCO in LiX/TFEP, being much higher than that observed in conventional LIB electrolyte solutions, shows the order of BF 4 < PF 6 < TFSA. The addition of ethylene carbonate (EC) to LiX/TFEP increases the ionic conductivity, which is probably caused by changes in the Li + -solvation structure in TFEP. The overvoltage for the Li-desertion/insertion of LCO is much lowered by the addition of EC to LiX/TFEP.

Magnetic sensor for building structural vibrations.

PubMed

García, Alfonso; Morón, Carlos; Tremps, Enrique

2014-02-05

This paper shows a new displacement-to-frequency transducer based on the variation of a coil inductance when a magnetic core is partially or completely inserted inside. This transducer is based on a Colpitts oscillator due its low manufacturing price, behavior and immunity to noise. A tank circuit with a configuration in parallel was used because it can be employed at lower frequencies and it enables it to make a direct analysis. The sensor has a dynamic range equal to the length of the coil. The cores can exchange sensors (coils with its ferromagnetic core) using the same electronic measuring system. In this way, with only an electronic circuit, the core sensor determines the measurement range. The obtained resolution is higher than 1/100,000, and the sensor also allows the measurement and knowing in real time the effect of vibration, thermal expansion, referred overload movements, etc.., that can occur in the structural elements of a building.

Method and apparatus for deflection measurements using eddy current effects

NASA Astrophysics Data System (ADS)

Chern, Engmin J.

1993-05-01

A method and apparatus for inserting and moving a sensing assembly with a mechanical positioning assembly to a desired remote location of a surface of a specimen under test and measuring angle and/or deflection by sensing the change in the impedance of at least one sensor coil located in a base plate which has a rotatable conductive plate pivotally mounted thereon so as to uncover the sensor coil(s) whose impedance changes as a function of deflection away from the center line of the base plate in response to the movement of the rotator plate when contacting the surface of the specimen under test is presented. The apparatus includes the combination of a system controller, a sensing assembly, an eddy current impedance measuring apparatus, and a mechanical positioning assembly driven by the impedance measuring apparatus to position the sensing assembly at a desired location of the specimen.

Magnetic Sensor for Building Structural Vibrations

PubMed Central

García, Alfonso; Morón, Carlos; Tremps, Enrique

2014-01-01

This paper shows a new displacement-to-frequency transducer based on the variation of a coil inductance when a magnetic core is partially or completely inserted inside. This transducer is based on a Colpitts oscillator due its low manufacturing price, behavior and immunity to noise. A tank circuit with a configuration in parallel was used because it can be employed at lower frequencies and it enables it to make a direct analysis. The sensor has a dynamic range equal to the length of the coil. The cores can exchange sensors (coils with its ferromagnetic core) using the same electronic measuring system. In this way, with only an electronic circuit, the core sensor determines the measurement range. The obtained resolution is higher than 1/100,000, and the sensor also allows the measurement and knowing in real time the effect of vibration, thermal expansion, referred overload movements, etc.., that can occur in the structural elements of a building. PMID:24504104

Method and apparatus for deflection measurements using eddy current effects

NASA Technical Reports Server (NTRS)

Chern, Engmin J. (Inventor)

1993-01-01

A method and apparatus for inserting and moving a sensing assembly with a mechanical positioning assembly to a desired remote location of a surface of a specimen under test and measuring angle and/or deflection by sensing the change in the impedance of at least one sensor coil located in a base plate which has a rotatable conductive plate pivotally mounted thereon so as to uncover the sensor coil(s) whose impedance changes as a function of deflection away from the center line of the base plate in response to the movement of the rotator plate when contacting the surface of the specimen under test is presented. The apparatus includes the combination of a system controller, a sensing assembly, an eddy current impedance measuring apparatus, and a mechanical positioning assembly driven by the impedance measuring apparatus to position the sensing assembly at a desired location of the specimen.

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.

Differential Editosome Protein Function between Life Cycle Stages of Trypanosoma brucei *

PubMed Central

McDermott, Suzanne M.; Guo, Xuemin; Carnes, Jason; Stuart, Kenneth

2015-01-01

Uridine insertion and deletion RNA editing generates functional mitochondrial mRNAs in Trypanosoma brucei. The mRNAs are differentially edited in bloodstream form (BF) and procyclic form (PF) life cycle stages, and this correlates with the differential utilization of glycolysis and oxidative phosphorylation between the stages. The mechanism that controls this differential editing is unknown. Editing is catalyzed by multiprotein ∼20S editosomes that contain endonuclease, 3′-terminal uridylyltransferase, exonuclease, and ligase activities. These editosomes also contain KREPB5 and KREPA3 proteins, which have no functional catalytic motifs, but they are essential for parasite viability, editing, and editosome integrity in BF cells. We show here that repression of KREPB5 or KREPA3 is also lethal in PF, but the effects on editosome structure differ from those in BF. In addition, we found that point mutations in KREPB5 or KREPA3 differentially affect cell growth, editosome integrity, and RNA editing between BF and PF stages. These results indicate that the functions of KREPB5 and KREPA3 editosome proteins are adjusted between the life cycle stages. This implies that these proteins are involved in the processes that control differential editing and that the 20S editosomes differ between the life cycle stages. PMID:26304125

Stimulation of ovarian stem cells by follicle stimulating hormone and basic fibroblast growth factor during cortical tissue culture.

PubMed

Parte, Seema; Bhartiya, Deepa; Manjramkar, Dhananjay D; Chauhan, Anahita; Joshi, Amita

2013-04-01

Cryopreserved ovarian cortical tissue acts as a source of primordial follicles (PF) which can either be auto-transplanted or cultured in vitro to obtain mature oocytes. This offers a good opportunity to attain biological parenthood to individuals with gonadal insufficiency including cancer survivors. However, role of various intra- and extra-ovarian factors during PF growth initiation still remain poorly understood. Ovarian biology has assumed a different dimension due to emerging data on presence of pluripotent very small embryonic-like stem cells (VSELs) and ovarian germ stem cells (OGSCs) in ovary surface epithelium (OSE) and the concept of postnatal oogenesis. The present study was undertaken to decipher effect of follicle stimulating hormone (FSH) and basic fibroblast growth factor (bFGF) on the growth initiation of PF during organ culture with a focus on ovarian stem cells. Serum-free cultures of marmoset (n=3) and human (young and peri-menopausal) ovarian cortical tissue pieces were established. Cortical tissue pieces stimulated with FSH (0.5 IU/ml) or bFGF (100 ng/ml) were collected on Day 3 for histological and molecular studies. Gene transcripts specific for pluripotency (Oct-4A, Nanog), early germ cells (Oct-4, c-Kit, Vasa) and to reflect PF growth initiation (oocyte-specific Gdf-9 and Lhx8, and granulosa cells specific Amh) were studied by q-RTPCR. A prominent proliferation of OSE (which harbors stem cells) and transition of PF to primary follicles was observed after FSH and bFGF treatment. Ovarian stem cells were found to be released on the culture inserts and retained the potential to spontaneously differentiate into oocyte-like structures in extended cultures. q-RTPCR analysis revealed an increased expression of gene transcripts specific for VSELs, OGSCs and early germ cells suggestive of follicular transition. The present study shows that both FSH and bFGF stimulate stem cells present in OSE and also lead to PF growth initiation. Thus besides being a source of PF, cryopreserved ovarian cortical tissue could also be a source of stem cells which retain the ability to spontaneously differentiate into oocyte-like structures in vitro. Results provide a paradigm shift in the basic understanding of FSH action and also offer a new perspective to the field of oncofertility research.

Solution 1H NMR determination of secondary structure for the three-iron form of ferredoxin from the hyperthermophilic archaeon Pyrococcus furiosus.

PubMed

Teng, Q; Zhou, Z H; Smith, E T; Busse, S C; Howard, J B; Adams, M W; La Mar, G N

1994-05-24

Two-dimensional 1H NMR data have been used to make sequence-specific assignments and define the secondary structure of the three-iron form of the oxidized ferredoxin, Fd, from the hyperthermophilic archaeon Pyrococcus furiosus, Pf. Signals for at least some protons were located for 65 of the 66 amino acids in the sequence, in spite of the paramagnetic (S = 1/2) ground state, but not all could be assigned. Unassigned and missing signals could be qualitatively correlated with the expected proximity of the protons to the paramagnetic cluster. The secondary structure was deduced from qualitative analysis of the 2D nuclear Overhauser effect, which identified two antiparallel beta-sheets, one triple-stranded including Ala1-Ser5, Val39-Glu41, and Thr62-Ala66, and one double-stranded consisting of Glu26-Asn28 and Lys32-Glu34, as well as an alpha-helix involving Glu43-Glu54. Three tight type I turns are located at residues Asp7-Thr10, Pro22-Phe25, and Asp29-Gly31. Comparison with the crystal structure of Desulfovibrio gigas, Dg, Fd (Kissinger et al., 1991) reveals a very similar folding topology, although several secondary structural elements are extended in Pf relative to Dg Fd. Thus the beta-sheet involving the two termini is expanded to include the two terminal residues and incorporates a third strand from the internal loop that is lengthened by several insertions in Pf relative to Dg Fd. The double-stranded beta-sheet in the interior of Pf Fd is lengthened slightly due to a much tighter type I turn between the two strands. The helix near the C-terminus is three residues longer in Pf than in Dg Fd, as well as being shifted toward the N-terminus. The disulfide link between the two nonligating Cys residues (Cys21 and Cys48) is conserved in Pf Fd, but the link near the C-terminus is in the middle of the long alpha-helix in Pf Fd, instead of at the N-terminus of the helix as in Dg Fd. The extensions of the beta-sheets and alpha-helix increase the number of main-chain hydrogen bonds in Pf Fd by approximately 8 relative to those in Dg Fd and likely contribute to its remarkable thermostability (it is unaffected by anaerobic incubation at 95 degrees C for 24 h).(ABSTRACT TRUNCATED AT 400 WORDS)

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.

The significant impact of framing coils on long-term outcomes in endovascular coiling for intracranial aneurysms: how to select an appropriate framing coil.

PubMed

Ishida, Wataru; Sato, Masayuki; Amano, Tatsuo; Matsumaru, Yuji

2016-09-01

OBJECTIVE The importance of a framing coil (FC)-the first coil inserted into an aneurysm during endovascular coiling, also called a lead coil or a first coil-is recognized, but its impact on long-term outcomes, including recanalization and retreatment, is not well established. The purposes of this study were to test the hypothesis that the FC is a significant factor for aneurysmal recurrence and to provide some insights on appropriate FC selection. METHODS The authors retrospectively reviewed endovascular coiling for 280 unruptured intracranial aneurysms and gathered data on age, sex, aneurysm location, aneurysm morphology, maximal size, neck width, adjunctive techniques, recanalization, retreatment, follow-up periods, total volume packing density (VPD), volume packing density of the FC, and framing coil percentage (FCP; the percentage of FC volume in total coil volume) to clarify the associated factors for aneurysmal recurrence. RESULTS Of 236 aneurysms included in this study, 33 (14.0%) had recanalization, and 18 (7.6%) needed retreatment during a mean follow-up period of 37.7 ± 16.1 months. In multivariate analysis, aneurysm size (odds ratio [OR] = 1.29, p < 0.001), FCP < 32% (OR 3.54, p = 0.009), and VPD < 25% (OR 2.96, p = 0.015) were significantly associated with recanalization, while aneurysm size (OR 1.25, p < 0.001) and FCP < 32% (OR 6.91, p = 0.017) were significant predictors of retreatment. VPD as a continuous value or VPD with any cutoff value could not predict retreatment with statistical significance in multivariate analysis. CONCLUSIONS FCP, which is equal to the FC volume as a percentage of the total coil volume and is unaffected by the morphology of the aneurysm or the measurement error in aneurysm length, width, or height, is a novel predictor of recanalization and retreatment and is more significantly predictive of retreatment than VPD. To select FCs large enough to meet the condition of FCP ≥ 32% is a potential relevant factor for better long-term outcomes. These findings support our hypothesis that the FC is a significant factor for aneurysmal recurrence.

Spiral Countercurrent Chromatography

PubMed Central

Ito, Yoichiro; Knight, Martha; Finn, Thomas M.

2013-01-01

For many years, high-speed countercurrent chromatography conducted in open tubing coils has been widely used for the separation of natural and synthetic compounds. In this method, the retention of the stationary phase is solely provided by the Archimedean screw effect by rotating the coiled column in the centrifugal force field. However, the system fails to retain enough of the stationary phase for polar solvent systems such as the aqueous–aqueous polymer phase systems. To address this problem, the geometry of the coiled channel was modified to a spiral configuration so that the system could utilize the radially acting centrifugal force. This successfully improved the retention of the stationary phase. Two different types of spiral columns were fabricated: the spiral disk assembly, made by stacking multiple plastic disks with single or four interwoven spiral channels connected in series, and the spiral tube assembly, made by inserting the tetrafluoroethylene tubing into a spiral frame (spiral tube support). The capabilities of these column assemblies were successfully demonstrated by separations of peptides and proteins with polar two-phase solvent systems whose stationary phases had not been well retained in the earlier multilayer coil separation column for high-speed countercurrent chromatography. PMID:23833207

High-Speed, High-Power Active Control Coils for HBT-EP

NASA Astrophysics Data System (ADS)

Debono, Bryan

2010-11-01

We report the performance of a newly installed high-speed, high-power active control system for the application of non-symmetric magnetic fields and the study of rotating MHD and resistive wall modes in the HBTEP tokamak. The new control system consists of an array of 120 modular control coils and 40 solid-state, high-power amplifiers that can apply non-symmetric control fields that are more than 10 times larger than previous studies in HBT-EP and exceed 5% of the equilibrium poloidal field strength. Measurements of the current and field response of the control system are presented as a function of frequency and control coil geometry, and these demonstrate the effectiveness of the system to interact with both growing RWM instabilities and long-wavelength modes rotating with the plasma. We describe a research plan to study the interaction of both kink and tearing mode fluctuations with applied static and rotating magnetic perturbations while systematically changing the plasma rotation with a biased molybdenum electrode inserted into the edge plasma.

Design of High Field Solenoids made of High Temperature Superconductors

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

Bartalesi, Antonio; /Pisa U.

2010-12-01

This thesis starts from the analytical mechanical analysis of a superconducting solenoid, loaded by self generated Lorentz forces. Also, a finite element model is proposed and verified with the analytical results. To study the anisotropic behavior of a coil made by layers of superconductor and insulation, a finite element meso-mechanic model is proposed and designed. The resulting material properties are then used in the main solenoid analysis. In parallel, design work is performed as well: an existing Insert Test Facility (ITF) is adapted and structurally verified to support a coil made of YBa{sub 2}Cu{sub 3}O{sub 7}, a High Temperature Superconductormore » (HTS). Finally, a technological winding process was proposed and the required tooling is designed.« less

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.

Assessing the image quality of pelvic MR images acquired with a flat couch for radiotherapy treatment planning.

PubMed

McJury, M; O'Neill, A; Lawson, M; McGrath, C; Grey, A; Page, W; O'Sullivan, J M

2011-08-01

To improve the integration of MRI with radiotherapy treatment planning, our department fabricated a flat couch top for our MR scanner. Setting up using this couch top meant that the patients were physically higher up in the scanner and, posteriorly, a gap was introduced between the patient and radiofrequency coil. Phantom measurements were performed to assess the quantitative impact on image quality. A phantom was set up with and without the flat couch insert in place, and measurements of image uniformity and signal to noise were made. To assess clinical impact, six patients with pelvic cancer were recruited and scanned on both couch types. The image quality of pairs of scans was assessed by two consultant radiologists. The use of the flat couch insert led to a drop in image signal to noise of approximately 14%. Uniformity in the anteroposterior direction was affected the most, with little change in right-to-left and feet-to-head directions. All six patients were successfully scanned on the flat couch, although one patient had to be positioned with their arms by their sides. The image quality scores showed no statistically significant change between scans with and without the flat couch in place. Although the quantitative performance of the coil is affected by the integration of a flat couch top, there is no discernible deterioration of diagnostic image quality, as assessed by two consultant radiologists. Although the flat couch insert moved patients higher in the bore of the scanner, all patients in the study were successfully scanned.

Magnetic Resonance Imaging of the Codman Microsensor Transducer Used for Intraspinal Pressure Monitoring: Findings From the Injured Spinal Cord Pressure Evaluation Study.

PubMed

Phang, Isaac; Mada, Marius; Kolias, Angelos G; Newcombe, Virginia F J; Trivedi, Rikin A; Carpenter, Adrian; Hawkes, Rob C; Papadopoulos, Marios C

2016-05-01

Laboratory and human study. To test the Codman Microsensor Transducer (CMT) in a cervical gel phantom. To test the CMT inserted to monitor intraspinal pressure in a patient with spinal cord injury. We recently introduced the technique of intraspinal pressure monitoring using the CMT to guide management of traumatic spinal cord injury [Werndle et al. Crit Care Med 2014;42:646]. This is analogous to intracranial pressure monitoring to guide management of patients with traumatic brain injury. It is unclear whether magnetic resonance imaging (MRI) of patients with spinal cord injury is safe with the intraspinal pressure CMT in situ. We measured the heating produced by the CMT placed in a gel phantom in various configurations. A 3-T MRI system was used with the body transmit coil and the spine array receive coil. A CMT was then inserted subdurally at the injury site in a patient who had traumatic spinal cord injury and MRI was performed at 1.5 T. In the gel phantom, heating of up to 5°C occurred with the transducer wire placed straight through the magnet bore. The heating was abolished when the CMT wire was coiled and passed away from the bore. We then tested the CMT in a patient with an American Spinal Injuries Association grade C cervical cord injury. The CMT wire was placed in the configuration that abolished heating in the gel phantom. Good-quality T1 and T2 images of the cord were obtained without neurological deterioration. The transducer remained functional after the MRI. Our data suggest that the CMT is MR conditional when used in the spinal configuration in humans. Data from a large patient group are required to confirm these findings. N/A.

Numerical analysis of modified Central Solenoid insert design

DOE PAGES

Khodak, Andrei; Martovetsky, Nicolai; Smirnov, Aleksandre; ...

2015-06-21

The United States ITER Project Office (USIPO) is responsible for fabrication of the Central Solenoid (CS) for ITER project. The ITER machine is currently under construction by seven parties in Cadarache, France. The CS Insert (CSI) project should provide a verification of the conductor performance in relevant conditions of temperature, field, currents and mechanical strain. The US IPO designed the CSI that will be tested at the Central Solenoid Model Coil (CSMC) Test Facility at JAEA, Naka. To validate the modified design we performed three-dimensional numerical simulations using coupled solver for simultaneous structural, thermal and electromagnetic analysis. Thermal and electromagneticmore » simulations supported structural calculations providing necessary loads and strains. According to current analysis design of the modified coil satisfies ITER magnet structural design criteria for the following conditions: (1) room temperature, no current, (2) temperature 4K, no current, (3) temperature 4K, current 60 kA direct charge, and (4) temperature 4K, current 60 kA reverse charge. Fatigue life assessment analysis is performed for the alternating conditions of: temperature 4K, no current, and temperature 4K, current 45 kA direct charge. Results of fatigue analysis show that parts of the coil assembly can be qualified for up to 1 million cycles. Distributions of the Current Sharing Temperature (TCS) in the superconductor were obtained from numerical results using parameterization of the critical surface in the form similar to that proposed for ITER. Lastly, special ADPL scripts were developed for ANSYS allowing one-dimensional representation of TCS along the cable, as well as three-dimensional fields of TCS in superconductor material. Published by Elsevier B.V.« less

Characterization of the ITER CS conductor and projection to the ITER CS performance

DOE PAGES

Martovetsky, N.; Isono, T.; Bessette, D.; ...

2017-06-20

The ITER Central Solenoid (CS) is one of the critical elements of the machine. The CS conductor went through an intense optimization and qualification program, which included characterization of the strands, a conductor straight short sample testing in the SULTAN facility at the Swiss Plasma Center (SPC), Villigen, Switzerland, and a single-layer CS Insert coil recently tested in the Central Solenoid Model Coil (CSMC) facility in QST-Naka, Japan. In this paper, we obtained valuable data in a wide range of the parameters (current, magnetic field, temperature, and strain), which allowed a credible characterization of the CS conductor in different conditions.more » Finally, using this characterization, we will make a projection to the performance of the CS in the ITER reference scenario.« less

Characterization of the ITER CS conductor and projection to the ITER CS performance

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

Martovetsky, N.; Isono, T.; Bessette, D.

The ITER Central Solenoid (CS) is one of the critical elements of the machine. The CS conductor went through an intense optimization and qualification program, which included characterization of the strands, a conductor straight short sample testing in the SULTAN facility at the Swiss Plasma Center (SPC), Villigen, Switzerland, and a single-layer CS Insert coil recently tested in the Central Solenoid Model Coil (CSMC) facility in QST-Naka, Japan. In this paper, we obtained valuable data in a wide range of the parameters (current, magnetic field, temperature, and strain), which allowed a credible characterization of the CS conductor in different conditions.more » Finally, using this characterization, we will make a projection to the performance of the CS in the ITER reference scenario.« less

Development of Bend Sensor for Catheter Tip

NASA Astrophysics Data System (ADS)

Nagano, Yoshitaka; Sano, Akihito; Fujimoto, Hideo

Recently, a minimally invasive surgery which makes the best use of the catheter has been becoming more popular. In endovascular coil embolization for a cerebral aneurysm, the observation of the catheter's painting phenomenon is very important to execute the appropriate manipulation of the delivery wire and the catheter. In this study, the internal bend sensor which consists of at least two bending enhanced plastic optical fibers was developed in order to measure the curvature of the catheter tip. Consequently, the painting could be more sensitively detected in the neighborhood of the aneurysm. In this paper, the basic characteristics of the developed sensor system are described and its usefulness is confirmed from the comparison of the insertion force of delivery wire and the curvature of catheter tip in the experiment of coil embolization.

Gradient and shim technologies for ultra high field MRI

PubMed Central

Winkler, Simone A.; Schmitt, Franz; Landes, Hermann; DeBever, Josh; Wade, Trevor; Alejski, Andrew

2017-01-01

Ultra High Field (UHF) MRI requires improved gradient and shim performance to fully realize the promised gains (SNR as well as spatial, spectral, diffusion resolution) that higher main magnetic fields offer. Both the more challenging UHF environment by itself, as well as the higher currents used in high performance coils, require a deeper understanding combined with sophisticated engineering modeling and construction, to optimize gradient and shim hardware for safe operation and for highest image quality. This review summarizes the basics of gradient and shim technologies, and outlines a number of UHF-related challenges and solutions. In particular, Lorentz forces, vibroacoustics, eddy currents, and peripheral nerve stimulation are discussed. Several promising UHF-relevant gradient concepts are described, including insertable gradient coils aimed at higher performance neuroimaging. PMID:27915120

Menstruum induces changes in mesothelial cell morphology.

PubMed

Koks, C A; Demir Weusten, A Y; Groothuis, P G; Dunselman, G A; de Goeij, A F; Evers, J L

2000-01-01

In previous studies, we have shown that menstrual endometrium preferentially adheres to the subepithelial lining of the peritoneum. It remains to be elucidated, however, whether this damage is preexisting or inflicted by the menstrual tissue itself. We hypothesized that the menstrual tissue itself damages the peritoneum. To investigate this, the viability of menstrual endometrial tissue in peritoneal fluid (PF) was evaluated and the morphologic changes in the mesothelial cells were studied by in vitro cocultures of menstruum with mesothelial cell monolayers. Menstruum was collected with a menstrual cup. Endometrial tissue was isolated from the menstruum, resuspended in culture medium or in the cell-free fraction of PF and cultured for 24, 48 or 72 h. A 3(4, 5-dimethylthiazolyl-2)-2,5-diphenyl tetrazolium bromide (MTT) assay was performed to obtain a relative measure of viable adhered endometrial cells. Mesothelial cells isolated from human omental tissue were cultured on Matrigel or uncoated plastic. At confluence, overnight cocultures were performed and scanning electron microscopy was used to evaluate the morphologic changes. The viability of endometrial fragments was 84% (n = 36, p < 0.05), 82% (n = 27, not significant) and 104% (n = 14, not significant) when cultured in the cell-free fraction of PF for 24, 48 and 72 h, respectively, when compared to medium with 10% fetal calf serum. Menstrual endometrial fragments or menstrual serum added to and cocultured with mesothelial cells induced severe morphologic alterations of the latter, including retraction, shrinking and gap formation. Similar morphologic changes were observed when mesothelial cells were cocultured with menstrual endometrial fragments in PF or in culture inserts. Incubation with conditioned medium from cultured menstrual endometrium induced similar but less pronounced changes in morphology. In conclusion, menstrual endometrial fragments remain viable in PF in vitro for at least 72 h. Antegradely shed menstruum induces changes in mesothelial cell morphology, including retraction and shrinking with exposure of the underlying surface. These findings suggest that menstruum is harmful to the peritoneal lining. Therefore, by local destruction of the mesothelial layer, menstrual endometrium is able to create sites for adhesion. Copyright 2000 S. Karger AG, Basel

Development of PET/MRI with insertable PET for simultaneous PET and MR imaging of human brain.

PubMed

Jung, Jin Ho; Choi, Yong; Jung, Jiwoong; Kim, Sangsu; Lim, Hyun Keong; Im, Ki Chun; Oh, Chang Hyun; Park, Hyun-wook; Kim, Kyung Min; Kim, Jong Guk

2015-05-01

The purpose of this study was to develop a dual-modality positron emission tomography (PET)/magnetic resonance imaging (MRI) with insertable PET for simultaneous PET and MR imaging of the human brain. The PET detector block was composed of a 4 × 4 matrix of detector modules, each consisting of a 4 × 4 array LYSO coupled to a 4 × 4 Geiger-mode avalanche photodiode (GAPD) array. The PET insert consisted of 18 detector blocks, circularly mounted on a custom-made plastic base to form a ring with an inner diameter of 390 mm and axial length of 60 mm. The PET gantry was shielded with gold-plated conductive fabric tapes with a thickness of 0.1 mm. The charge signals of PET detector transferred via 4 m long flat cables were fed into the position decoder circuit. The flat cables were shielded with a mesh-type aluminum sheet with a thickness of 0.24 mm. The position decoder circuit and field programmable gate array-embedded DAQ modules were enclosed in an aluminum box with a thickness of 10 mm and located at the rear of the MR bore inside the MRI room. A 3-T human MRI system with a Larmor frequency of 123.7 MHz and inner bore diameter of 60 cm was used as the PET/MRI hybrid system. A custom-made radio frequency (RF) coil with an inner diameter of 25 cm was fabricated. The PET was positioned between gradient and the RF coils. PET performance was measured outside and inside the MRI scanner using echo planar imaging, spin echo, turbo spin echo, and gradient echo sequences. MRI performance was also evaluated with and without the PET insert. The stability of the newly developed PET insert was evaluated and simultaneous PET and MR images of a brain phantom were acquired. No significant degradation of the PET performance caused by MR was observed when the PET was operated using various MR imaging sequences. The signal-to-noise ratio of MR images was slightly degraded due to the PET insert installed inside the MR bore while the homogeneity was maintained. The change of gain of the 256 GAPD/scintillator elements of a detector block was <3% for 60 min, and simultaneous PET and MR images of a brain phantom were successfully acquired. Experimental results indicate that a compact and lightweight PET insert for hybrid PET/MRI can be developed using GAPD arrays and charge signal transmission method proposed in this study without significant interference.

Absolute Ethanol Embolisation of Mandibular Arteriovenous Malformations Following Direct Percutaneous Puncture and Release of Coils via a Microcatheter.

PubMed

Wang, D; Su, L; Han, Y; Wang, Z; Zheng, L; Fan, X

2017-06-01

To evaluate the safety, efficacy, and medium-term outcome of a modified technique of ethanol embolisation of mandibular arteriovenous malformations (AVMs) following a direct percutaneous transvenous approach to the release of coils via a microcatheter. From January 2012 to July 2014, 18 consecutive patients (mean age 20.9 years [range 10-35 years]) with symptomatic AVMs of the mandible were enrolled. A microcatheter was inserted into the lesion via a direct percutaneous puncture needle. Electrolytically detachable coils and 0.018 mm coils were super-selectively placed to decrease the flow and volume of the arteriovenous fistulas via a microcatheter. Absolute ethanol was injected to obliterate the fistulas. Clinical follow-up was performed in all patients. Therapeutic outcomes were determined by evaluating the degree of devascularisation at follow-up angiography and symptoms and signs. Transvenous release of coils combined with absolute ethanol embolisation were used in all cases. The amount of ethanol used ranged from 5 to 50 mL (mean 25.7 mL) in a single session. Sixteen of 18 patients were cured, and two had partial remission. Follow-up times ranged from 8 to 26 months (medium 15.7 months), and there was no angiographic recurrence of the lesions. Minor complication occurred in five of the 18 patients. There were no major complications. Absolute ethanol embolisation following a direct percutaneous transvenous approach to release coils via a microcatheter is a feasible, safe, and highly effective method for the management of mandibular AVMs. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

High-Field Quench Behavior and Protection of $$Bi_2 Sr_2 Ca Cu_2 O_x$$ Coils: Minimum and Maximum Quench Detection Voltages

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

Shen, Tengming; Ye, Liyang; Turrioni, Daniele

Small insert coils have been built using a multifilamentary Bi2Sr2CaCu2Ox round wire, and characterized in background fields to explore the quench behaviors and limits of Bi2Sr2CaCu2Ox superconducting magnets, with an emphasis on assessing the impact of slow normal zone propagation on quench detection. Using heaters of various lengths to initiate a small normal zone, a coil was quenched safely more than 70 times without degradation, with the maximum coil temperature reaching 280 K. Coils withstood a resistive voltage of tens of mV for seconds without quenching, showing the high stability of these coils and suggesting that the quench detection voltagemore » shall be greater than 50 mV to not to falsely trigger protection. The hot spot temperature for the resistive voltage of the normal zone to reach 100 mV increases from ~40 K to ~80 K with increasing the operating wire current density Jo from 89 A/mm2 to 354 A/mm2 whereas for the voltage to reach 1 V, it increases from ~60 K to ~140 K, showing the increasing negative impact of slow normal zone propagation on quench detection with increasing Jo and the need to limit the quench detection voltage to < 1 V. These measurements, coupled with an analytical quench model, were used to access the impact of the maximum allowable voltage and temperature upon quench detection on the quench protection, assuming to limit the hot spot temperature to <300 K.« less

Lambda Probe Measurements of Laboratory Spheromaks

NASA Astrophysics Data System (ADS)

Jorne, E.; Bellan, P. M.; Hsu, S. C.; Moynihan, C.

2003-10-01

A combined current and magnetic probe (lambda probe) has been constructed and is being tested for the purpose of investigating the behavior of spheromaks formed by the Caltech planar spheromak gun. The probe consists of a 1.5cm diameter, 52 turn Rogowski coil and a single loop magnetic coil, housed in a ceramic shell attached to a 95cm long hollow, steel shaft. A high voltage power supply was used to test the probe's ability to measure pulsed currents with submicrosecond rise times. A calibrated current pulse was provided by a 1μF capacitor discharged by a krytron switch to a low inductance circuit. Magnetic calibration was obtained by using the capacitor bank to power a 16cm diameter Helmholtz coil. Both magnetic and current calibration were in good agreement with estimates based on geometry. An existing steel shaft will be replaced by a ceramic shaft in order to minimize undesired effects on the plasma by a conductor. Once sealed with epoxy, the probe will be ready for insertion into the vacuum chamber and used to measure the magnetic field and parallel current during spheromak formation.

Performance Improvement of a Magnetized Coaxial Plasma Gun by adopting Iron-core Bias Coil and New Pre-Ionization System

NASA Astrophysics Data System (ADS)

Edo, Takahiro; Asai, T.; Tanaka, F.; Yamada, S.; Hosozawa, A.; Gota, H.; Roche, T.; Allfrey, I.; Matsumoto, T.

2017-10-01

A magnetized coaxial plasma gun (MCPG) is a device used to generate a compact toroid (CT), which has a spheromak-like configuration. A typical MCPG consists of a set of axisymmetric cylindrical electrodes, bias coil, and gas-puff valves. In order to expand the CT operating range, the distributions of the bias magnetic field and neutral gas have been investigated. We have developed a new means of generating stuffing flux. By inserting an iron core into the bias coil, the magnetic field increases dramatically; even a small current of a few Amps produces a sufficient bias field. According to a simulation result, it was also suggested that the radial distribution of the bias field is easily controlled. The ejected CT and the target FRC are cooled by excess neutral gas that typical MCPGs require to initiate a breakdown; therefore, we have adopted a miniature gun as a new pre-ionization (PI) system. By introducing this PI system, the breakdown occurs at lower neutral gas density so that the amount of excess neutral gas can be reduced.

Conceptual design of a cryogen-free μMRI device

NASA Astrophysics Data System (ADS)

Authelet, G.; Poirier-Quinot, M.; Ginefri, J.-C.; Bonelli, A.; Baudouy, B.

2017-12-01

To perform Micro Magnetic Resonance Imaging (mMRI) analysis on small regions such as skins, articulations or small animals, the required spatial resolution implies to dramatically improve the sensitivity of the detection. One way to go is to use small radio-frequency superconducting coil that allow, among others, increasing significantly the signal-to-noise ratio. The RF probe, constituted of an optimized YBaCuO film coil cooled below nitrogen temperature, must be located no further than few millimeters from the biological region to be imaged in a clinical MRI magnet. To fulfill the medical environment and constraints, a cryogen-free cooling scheme has been developed to maintain the superconducting coil at the working temperature. The cryogenic design is based on a pulse tube cryocooler and solid thermal links inserted in a non-magnetic cryostat to avoid creating any electromagnetic perturbations to the MRI magnet and the measurements. We report here the conceptual design of the cryogenic system with the required thermal performances, the corresponding layout and architecture of the system as well as the main technical challenges met for the construction.

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

Magnetostatic focal spot correction for x-ray tubes operating in strong magnetic fields using iterative optimization

PubMed Central

Lillaney, Prasheel; Shin, Mihye; Conolly, Steven M.; Fahrig, Rebecca

2012-01-01

Purpose: Combining x-ray fluoroscopy and MR imaging systems for guidance of interventional procedures has become more commonplace. By designing an x-ray tube that is immune to the magnetic fields outside of the MR bore, the two systems can be placed in close proximity to each other. A major obstacle to robust x-ray tube design is correcting for the effects of the magnetic fields on the x-ray tube focal spot. A potential solution is to design active shielding that locally cancels the magnetic fields near the focal spot. Methods: An iterative optimization algorithm is implemented to design resistive active shielding coils that will be placed outside the x-ray tube insert. The optimization procedure attempts to minimize the power consumption of the shielding coils while satisfying magnetic field homogeneity constraints. The algorithm is composed of a linear programming step and a nonlinear programming step that are interleaved with each other. The coil results are verified using a finite element space charge simulation of the electron beam inside the x-ray tube. To alleviate heating concerns an optimized coil solution is derived that includes a neodymium permanent magnet. Any demagnetization of the permanent magnet is calculated prior to solving for the optimized coils. The temperature dynamics of the coil solutions are calculated using a lumped parameter model, which is used to estimate operation times of the coils before temperature failure. Results: For a magnetic field strength of 88 mT, the algorithm solves for coils that consume 588 A/cm2. This specific coil geometry can operate for 15 min continuously before reaching temperature failure. By including a neodymium magnet in the design the current density drops to 337 A/cm2, which increases the operation time to 59 min. Space charge simulations verify that the coil designs are effective, but for oblique x-ray tube geometries there is still distortion of the focal spot shape along with deflections of approximately 3 mm in the radial and circumferential directions on the anode. Conclusions: Active shielding is an attractive solution for correcting the effects of magnetic fields on the x-ray focal spot. If extremely long fluoroscopic exposure times are required, longer operation times can be achieved by including a permanent magnet with the active shielding design. PMID:22957623

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.

The MINDView brain PET detector, feasibility study based on SiPM arrays

NASA Astrophysics Data System (ADS)

González, Antonio J.; Majewski, Stan; Sánchez, Filomeno; Aussenhofer, Sebastian; Aguilar, Albert; Conde, Pablo; Hernández, Liczandro; Vidal, Luis F.; Pani, Roberto; Bettiol, Marco; Fabbri, Andrea; Bert, Julien; Visvikis, Dimitris; Jackson, Carl; Murphy, John; O'Neill, Kevin; Benlloch, Jose M.

2016-05-01

The Multimodal Imaging of Neurological Disorders (MINDView) project aims to develop a dedicated brain Positron Emission Tomography (PET) scanner with sufficient resolution and sensitivity to visualize neurotransmitter pathways and their disruptions in mental disorders for diagnosis and follow-up treatment. The PET system should be compact and fully compatible with a Magnetic Resonance Imaging (MRI) device in order to allow its operation as a PET brain insert in a hybrid imaging setup with most MRI scanners. The proposed design will enable the currently-installed MRI base to be easily upgraded to PET/MRI systems. The current design for the PET insert consists of a 3-ring configuration with 20 modules per ring and an axial field of view of ~15 cm and a geometrical aperture of ~33 cm in diameter. When coupled to the new head Radio Frequency (RF) coil, the inner usable diameter of the complete PET-RF coil insert is reduced to 26 cm. Two scintillator configurations have been tested, namely a 3-layer staggered array of LYSO with 1.5 mm pixel size, with 35×35 elements (6 mm thickness each) and a black-painted monolithic LYSO block also covering about 50×50 mm2 active area with 20 mm thickness. Laboratory test results associated with the current MINDView PET module concept are presented in terms of key parameters' optimization, such as spatial and energy resolution, sensitivity and Depth of Interaction (DOI) capability. It was possible to resolve all pixel elements from the three scintillator layers with energy resolutions as good as 10%. The monolithic scintillator showed average detector resolutions varying from 3.5 mm in the entrance layer to better than 1.5 mm near the photosensor, with average energy resolutions of about 17%.

A Digital Preclinical PET/MRI Insert and Initial Results.

PubMed

Weissler, Bjoern; Gebhardt, Pierre; Dueppenbecker, Peter M; Wehner, Jakob; Schug, David; Lerche, Christoph W; Goldschmidt, Benjamin; Salomon, Andre; Verel, Iris; Heijman, Edwin; Perkuhn, Michael; Heberling, Dirk; Botnar, Rene M; Kiessling, Fabian; Schulz, Volkmar

2015-11-01

Combining Positron Emission Tomography (PET) with Magnetic Resonance Imaging (MRI) results in a promising hybrid molecular imaging modality as it unifies the high sensitivity of PET for molecular and cellular processes with the functional and anatomical information from MRI. Digital Silicon Photomultipliers (dSiPMs) are the digital evolution in scintillation light detector technology and promise high PET SNR. DSiPMs from Philips Digital Photon Counting (PDPC) were used to develop a preclinical PET/RF gantry with 1-mm scintillation crystal pitch as an insert for clinical MRI scanners. With three exchangeable RF coils, the hybrid field of view has a maximum size of 160 mm × 96.6 mm (transaxial × axial). 0.1 ppm volume-root-mean-square B 0-homogeneity is kept within a spherical diameter of 96 mm (automatic volume shimming). Depending on the coil, MRI SNR is decreased by 13% or 5% by the PET system. PET count rates, energy resolution of 12.6% FWHM, and spatial resolution of 0.73 mm (3) (isometric volume resolution at isocenter) are not affected by applied MRI sequences. PET time resolution of 565 ps (FWHM) degraded by 6 ps during an EPI sequence. Timing-optimized settings yielded 260 ps time resolution. PET and MR images of a hot-rod phantom show no visible differences when the other modality was in operation and both resolve 0.8-mm rods. Versatility of the insert is shown by successfully combining multi-nuclei MRI ((1)H/(19)F) with simultaneously measured PET ((18)F-FDG). A longitudinal study of a tumor-bearing mouse verifies the operability, stability, and in vivo capabilities of the system. Cardiac- and respiratory-gated PET/MRI motion-capturing (CINE) images of the mouse heart demonstrate the advantage of simultaneous acquisition for temporal and spatial image registration.

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.

[Tentorial Dural Arteriovenous Fistula Successfully Treated with Transvenous Embolization Using a Double Catheterization Technique through Venous Drainage:A Case Report].

PubMed

Yamakawa, Akira; Fujita, Atsushi; Tanaka, Hirotomo; Ikeda, Mitsuru; Morikawa, Masashi; Kohmura, Eiji

2017-07-01

Tentorial dural arteriovenous fistulas(dAVFs)are a rare clinical entity accounting for less than 10% of all intracranial dAVFs. Because these lesions are characterized by high hemorrhagic risk, aggressive treatment should be considered. Although the number of reported cases treated with endovascular transarterial embolization(TAE)using glue has been increasing, little is known about the transvenous approach. Here, we report the case of a patient with a tentorial dAVF who was successfully treated with transvenous embolization(TVE)through venous drainage using a double catheterization technique. A 68-year-old male patient who had a history of left putaminal hemorrhage treated with a craniotomy was diagnosed with a tentorial dAVF on a magnetic resonance angiogram. Because the patient refused another craniotomy for surgical interruption of the dAVF, an endovascular approach was considered. We first attempted to perform TAE with glue, but catheterization into the tortuous meningohypophyseal trunk failed. We then performed a TVE of the venous drainage near the shunt with detachable coils and achieved complete obliteration of the fistula. During coil embolization of the venous drainage, insertion of small coils near the shunt was supported by another anchor coil that was delivered using a double catheterization technique. The method of TVE through venous drainage using a double catheterization technique, which involved placing coils in the fragile drainage vein, was safe and effective in a case of tentorial dAVF. This technique should be considered as another option for the management of complex tentorial dAVFs.

Ureteric catheterization via an ileal conduit: technique and retrieval of a JJ stent.

PubMed

Wah, T M; Kellett, M J

2004-11-01

Retrograde ureteric catheterization of a patient with an ileal conduit is difficult, because guide wires and catheters coil in the conduit. A modified loopogram, using a Foley catheter as a fulcrum through which catheters can be advanced to the ureteric anastomosis, is described. This technique was used to remove a JJ stent, which had been inserted previously across a stricture in one ureter, the stent crossing from one kidney to the other.

NMR measurement system including two synchronized ring buffers, with 128 rf coils for in situ water monitoring in a polymer electrolyte fuel cell

NASA Astrophysics Data System (ADS)

Ogawa, Kuniyasu; Haishi, Tomoyuki; Aoki, Masaru; Hasegawa, Hiroshi; Morisaka, Shinichi; Hashimoto, Seitaro

2017-01-01

A small radio-frequency (rf) coil inserted into a polymer electrolyte fuel cell (PEFC) can be used to acquire nuclear magnetic resonance (NMR) signals from the water in a membrane electrode assembly (MEA) or in oxygen gas channels in the PEFC. Measuring the spatial distribution of the water in a large PEFC requires using many rf probes, so an NMR measurement system which acquires NMR signals from 128 rf probes at intervals of 0.5 s was manufactured. The system has eight rf transceiver units with a field-programmable gate array (FPGA) for modulation of the excitation pulse and quadrature phase detection of the NMR signal, and one control unit with two ring buffers for data control. The sequence data required for the NMR measurement were written into one ring buffer. The acquired NMR signal data were then written temporarily into the other ring buffer and then were transmitted to a personal computer (PC). A total of 98 rf probes were inserted into the PEFC that had an electrical generation area of 16 cm × 14 cm, and the water generated in the PEFC was measured when the PEFC operated at 100 A. As a result, time-dependent changes in the spatial distribution of the water content in the MEA and the water in the oxygen gas channels were obtained.

Development of PET/MRI with insertable PET for simultaneous PET and MR imaging of human brain

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

Jung, Jin Ho; Choi, Yong, E-mail: ychoi.image@gmail.com; Jung, Jiwoong

2015-05-15

Purpose: The purpose of this study was to develop a dual-modality positron emission tomography (PET)/magnetic resonance imaging (MRI) with insertable PET for simultaneous PET and MR imaging of the human brain. Methods: The PET detector block was composed of a 4 × 4 matrix of detector modules, each consisting of a 4 × 4 array LYSO coupled to a 4 × 4 Geiger-mode avalanche photodiode (GAPD) array. The PET insert consisted of 18 detector blocks, circularly mounted on a custom-made plastic base to form a ring with an inner diameter of 390 mm and axial length of 60 mm. Themore » PET gantry was shielded with gold-plated conductive fabric tapes with a thickness of 0.1 mm. The charge signals of PET detector transferred via 4 m long flat cables were fed into the position decoder circuit. The flat cables were shielded with a mesh-type aluminum sheet with a thickness of 0.24 mm. The position decoder circuit and field programmable gate array-embedded DAQ modules were enclosed in an aluminum box with a thickness of 10 mm and located at the rear of the MR bore inside the MRI room. A 3-T human MRI system with a Larmor frequency of 123.7 MHz and inner bore diameter of 60 cm was used as the PET/MRI hybrid system. A custom-made radio frequency (RF) coil with an inner diameter of 25 cm was fabricated. The PET was positioned between gradient and the RF coils. PET performance was measured outside and inside the MRI scanner using echo planar imaging, spin echo, turbo spin echo, and gradient echo sequences. MRI performance was also evaluated with and without the PET insert. The stability of the newly developed PET insert was evaluated and simultaneous PET and MR images of a brain phantom were acquired. Results: No significant degradation of the PET performance caused by MR was observed when the PET was operated using various MR imaging sequences. The signal-to-noise ratio of MR images was slightly degraded due to the PET insert installed inside the MR bore while the homogeneity was maintained. The change of gain of the 256 GAPD/scintillator elements of a detector block was <3% for 60 min, and simultaneous PET and MR images of a brain phantom were successfully acquired. Conclusions: Experimental results indicate that a compact and lightweight PET insert for hybrid PET/MRI can be developed using GAPD arrays and charge signal transmission method proposed in this study without significant interference.« less

Overexpression of biotin synthase and biotin ligase is required for efficient generation of sulfur-35 labeled biotin in E. coli.

PubMed

Delli-Bovi, Teegan A; Spalding, Maroya D; Prigge, Sean T

2010-10-11

Biotin is an essential enzyme cofactor that acts as a CO2 carrier in carboxylation and decarboxylation reactions. The E. coli genome encodes a biosynthetic pathway that produces biotin from pimeloyl-CoA in four enzymatic steps. The final step, insertion of sulfur into desthiobiotin to form biotin, is catalyzed by the biotin synthase, BioB. A dedicated biotin ligase (BirA) catalyzes the covalent attachment of biotin to biotin-dependent enzymes. Isotopic labeling has been a valuable tool for probing the details of the biosynthetic process and assaying the activity of biotin-dependent enzymes, however there is currently no established method for 35S labeling of biotin. In this study, we produced [35S]-biotin from Na35SO4 and desthiobiotin with a specific activity of 30.7 Ci/mmol, two orders of magnitude higher than previously published methods. The biotinylation domain (PfBCCP-79) from the Plasmodium falciparum acetyl-CoA carboxylase (ACC) was expressed in E. coli as a biotinylation substrate. We found that overexpression of the E. coli biotin synthase, BioB, and biotin ligase, BirA, increased PfBCCP-79 biotinylation 160-fold over basal levels. Biotinylated PfBCCP-79 was purified by affinity chromatography, and free biotin was liberated using acid hydrolysis. We verified that we had produced radiolabeled biologically active [D]-biotin that specifically labels biotinylated proteins through reuptake in E. coli. The strategy described in our report provides a simple and effective method for the production of [35S]-biotin in E. coli based on affinity chromatography.

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.

Discovery and Optimization of Imidazopyridine-Based Inhibitors of Diacylglycerol Acyltransferase 2 (DGAT2).

PubMed

Futatsugi, Kentaro; Kung, Daniel W; Orr, Suvi T M; Cabral, Shawn; Hepworth, David; Aspnes, Gary; Bader, Scott; Bian, Jianwei; Boehm, Markus; Carpino, Philip A; Coffey, Steven B; Dowling, Matthew S; Herr, Michael; Jiao, Wenhua; Lavergne, Sophie Y; Li, Qifang; Clark, Ronald W; Erion, Derek M; Kou, Kou; Lee, Kyuha; Pabst, Brandon A; Perez, Sylvie M; Purkal, Julie; Jorgensen, Csilla C; Goosen, Theunis C; Gosset, James R; Niosi, Mark; Pettersen, John C; Pfefferkorn, Jeffrey A; Ahn, Kay; Goodwin, Bryan

2015-09-24

The medicinal chemistry and preclinical biology of imidazopyridine-based inhibitors of diacylglycerol acyltransferase 2 (DGAT2) is described. A screening hit 1 with low lipophilic efficiency (LipE) was optimized through two key structural modifications: (1) identification of the pyrrolidine amide group for a significant LipE improvement, and (2) insertion of a sp(3)-hybridized carbon center in the core of the molecule for simultaneous improvement of N-glucuronidation metabolic liability and off-target pharmacology. The preclinical candidate 9 (PF-06424439) demonstrated excellent ADMET properties and decreased circulating and hepatic lipids when orally administered to dyslipidemic rodent models.

Development of remountable joints and heat removable techniques for high-temperature superconducting magnets

NASA Astrophysics Data System (ADS)

Hashizume, H.; Ito, S.; Yanagi, N.; Tamura, H.; Sagara, A.

2018-02-01

Segment fabrication is now a candidate for the design of superconducting helical magnets in the helical fusion reactor FFHR-d1, which adopts the joint winding of high-temperature superconducting (HTS) helical coils as a primary option and the ‘remountable’ HTS helical coil as an advanced option. This paper reports on recent progress in two key technologies: the mechanical joints (remountable joints) of the HTS conductors and the metal porous media inserted into the cooling channel for segment fabrication. Through our research activities it has been revealed that heat treatment during fabrication of the joint can reduce joint resistance and its dispersion, which can shorten the fabrication process and be applied to bent conductor joints. Also, heat transfer correlations of the cooling channel were established to evaluate heat transfer performance with various cryogenic coolants based on the correlations to analyze the thermal stability of the joint.

Design, Fabrication, and Test of a Superconducting Dipole Magnet Based on Tilted Solenoids

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

Caspi, S.; Dietderich, D. R.; Ferracin, P.

2007-06-01

It can be shown that, by superposing two solenoid-like thin windings that are oppositely skewed (tilted) with respect to the bore axis, the combined current density on the surface is 'cos-theta' like and the resulting magnetic field in the bore is a pure dipole. As a proof of principle, such a magnet was designed, built and tested as part of a summer undergraduate intern project. The measured field in the 25mm bore, 4 single strand layers using NbTi superconductor, exceeded 1 T. The simplicity of this high field quality design, void of typical wedges end-spacers and coil assembly, is especiallymore » suitable for insert-coils using High Temperature Superconducting wire as well as for low cost superconducting accelerator magnets for High Energy Physics. Details of the design, construction and test are reported.« less

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.

New Improvements in Magnetic Measurements Laboratory of the ALBA Synchrotron Facility

NASA Astrophysics Data System (ADS)

Campmany, Josep; Marcos, Jordi; Massana, Valentí

ALBA synchrotron facility has a complete insertion devices (ID) laboratory to characterize and produce magnetic devices needed to satisfy the requirements of ALBA's user community. The laboratory is equipped with a Hall-probe bench working in on-the-fly measurement mode allowing the measurement of field maps of big magnetic structures with high accuracy, both in magnetic field magnitude and position. The whole control system of this bench is based on TANGO. The Hall probe calibration range extends between sub-Gauss to 2 Tesla with an accuracy of 100 ppm. Apart from the Hall probe bench, the ID laboratory has a flipping coil bench dedicated to measuring field integrals and a Helmholtz coil bench specially designed to characterize permanent magnet blocks. Also, a fixed stretched wire bench is used to measure field integrals of magnet sets. This device is specifically dedicated to ID construction. Finally, the laboratory is equipped with a rotating coil bench, specially designed for measuring multipolar devices used in accelerators, such as quadrupoles, sextupoles, etc. Recent improvements of the magnetic measurements laboratory of ALBA synchrotron include the design and manufacturing of very thin 3D Hall probe heads, the design and manufacturing of coil sensors for the Rotating coil bench based on multilayered PCB, and the improvement of calibration methodology in order to improve the accuracy of the measurements. ALBA magnetic measurements laboratory is open for external contracts, and has been widely used by national and international institutes such as CERN, ESRF or CIEMAT, as well as magnet manufacturing companies, such as ANTEC, TESLA and I3 M. In this paper, we will present the main features of the measurement benches as well as improvements made so far.

Procedure-related haemorrhage in embolisation of intracranial aneurysms with Guglielmi detachable coils.

PubMed

Kwon, B J; Han, M H; Oh, C W; Kim, K H; Chang, K H

2003-08-01

We reviewed the haemorrhagic complications of the endovascular treatment of intracranial aneurysms, in terms of frequency, pre-embolisation clinical status, clinical and radiological manifestations, management and prognosis. In 275 patients treated for 303 aneurysms over 7 years we had seven (one man and six women--2.3%) with haemorrhage during or immediately after endovascular treatment. All procedures were performed with a standardised protocol of heparinisation and anaesthesia. Four had ruptured aneurysms, two at the tip of the basilar artery, and one ach on the internal carotid and posterior cerebral artery, treated after 12, 5, 14, and 2 days, respectively, three were in Hunt and Hess grade 2 and one in grade 1. Bleeding occurred during coiling in three, after placement of at least four coils, and during manipulation of the guidewire to enter the aneurysm in the fourth. Haemorrhage was manifest as extravasation of contrast medium, with a sudden rise in systolic blood pressure in three patients. The other three patients had unruptured aneurysms; they had stable blood pressure and angiographic findings during the procedure, but one, under sedation, had seizures immediately after insertion of four coils, and the other two had seizures, headache and vomiting on the day following the procedure. Heparin reversal with protamine sulphate was started promptly started when bleeding was detected in four patients, and the embolisation was completed with additional coils in three. Emergency ventricular drainage was performed in the two patients with ruptured aneurysm and one with an unruptured aneurysm who had abnormal neurological responses or hydrocephalus. The bleeding caused a third nerve palsy in one patient, which might have been due to ischaemia and progressively improved.

Applicability of contrast-enhanced ultrasound in the diagnosis of plantar fasciitis.

PubMed

Broholm, R; Pingel, J; Simonsen, L; Bülow, J; Johannsen, F

2017-12-01

Contrast-enhanced ultrasound (CEUS) is used to visualize the microvascularization in various tissues. The purpose of this study was to investigate whether CEUS could be used to visualize the microvascular volume (MV) in the plantar fascia, and to compare the method to clinical symptoms and B-mode ultrasound (US) in patients with plantar fasciitis (PF). Twenty patients with unilateral PF were included and were divided by US in insertional thickening (10), midsubstance thickening (5), and no US changes (5). The MV was measured simultaneously in both heels. Four areas in the plantar fascia and plantar fat pad were measured independently by two observers. Inter- and intra-observer correlation analyses were performed. The asymptomatic heels showed a constantly low MV, and for the whole group of patients, a significantly higher MV was found in the symptomatic plantar fascia and plantar fat pad. Inter-observer correlation as well as intra-observer agreement was excellent. The MV in the plantar fascia and plantar fat pad can be measured reliably using CEUS, suggesting that it is a reproducible method to examine patients with plantar fasciitis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Improved stability, magnetic field preservation and recovery speed in (RE)Ba2Cu3O x -based no-insulation magnets via a graded-resistance approach

NASA Astrophysics Data System (ADS)

Kan Chan, Wan; Schwartz, Justin

2017-07-01

The no-insulation (NI) approach to winding (RE)Ba2Cu3O x (REBCO) high temperature superconductor solenoids has shown significant promise for maximizing the efficient usage of conductor while providing self-protecting operation. Self-protection in a NI coil, however, does not diminish the likelihood that a recoverable quench occurs. During a disturbance resulting in a recoverable quench, owing to the low turn-to-turn contact resistance, transport current bypasses the normal zone by flowing directly from the current input lead to the output lead, leading to a near total loss of the azimuthal current responsible for magnetic field generation. The consequences are twofold. First, a long recovery process is needed to recharge the coil to full operational functionality. Second, a fast magnetic field transient is created due to the sudden drop in magnetic field in the quenching coil. The latter could induce a global inductive quench propagation in other coils of a multi-coil NI magnet, increasing the likelihood of quenching and accelerating the depletion of useful current in other coils, lengthening the post-quench recovery process. Here a novel graded-resistance method is proposed to tackle the mentioned problems while maintaining the superior thermal stability and self-protecting capability of NI magnets. Through computational modeling and analysis on a hybrid multiphysics model, patterned resistive-conductive layers are inserted between selected turn-to-turn contacts to contain hot-spot heat propagation while maintaining the turn-wise current sharing required for self-protection, resulting in faster post-quench recovery and reduced magnetic field transient. Effectiveness of the method is studied at 4.2 and 77 K. Through the proposed method, REBCO magnets with high current density, high thermal stability, low likelihood of quenching, and rapid, passive recovery emerge with high operational reliability and availability.

Detection of different kidney stone types: an ex vivo comparison of ultrashort echo time MRI to reference standard CT.

PubMed

Ibrahim, El-Sayed H; Cernigliaro, Joseph G; Pooley, Robert A; Bridges, Mellena D; Giesbrandt, Jamie G; Williams, James C; Haley, William E

2016-01-01

With the development of ultrashort echo time (UTE) sequences, it may now be possible to detect kidney stones by using magnetic resonance imaging (MRI). In this study, kidney stones of varying composition and sizes were imaged using both UTE MRI as well as the reference standard of computed tomography (CT), with different surrounding materials and scan setups. One hundred and fourteen kidney stones were inserted into agarose and urine phantoms and imaged both on a dual-energy CT (DECT) scanner using a standard renal stone imaging protocol and on an MRI scanner using the UTE sequence with both head and body surface coils. A subset of the stones representing all composition types and sizes was then inserted into the collecting system of porcine kidneys and imaged in vitro with both CT and MRI. All of the stones were visible on both CT and MRI imaging. DECT was capable of differentiating between uric acid and nonuric acid stones. In MRI imaging, the choice of coil and large field of view (FOV) did not affect stone detection or image quality. The MRI images showed good visualization of the stones' shapes, and the stones' dimensions measured from MRI were in good agreement with the actual values (R(2)=0.886, 0.895, and 0.81 in the agarose phantom, urine phantom, and pig kidneys, respectively). The measured T2 relaxation times ranged from 4.2 to 7.5ms, but did not show significant differences among different stone composition types. UTE MRI compared favorably with the reference standard CT for imaging stones of different composition types and sizes using body surface coil and large FOV, which suggests potential usefulness of UTE MRI in imaging kidney stones in vivo. Copyright © 2015 Elsevier Inc. All rights reserved.

Entropic benefit of a cross-link in protein association.

PubMed

Zaman, Muhammad H; Berry, R Stephen; Sosnick, Tobin R

2002-08-01

We introduce a method to estimate the loss of configurational entropy upon insertion of a cross-link to a dimeric system. First, a clear distinction is established between the loss of entropy upon tethering and binding, two quantities that are often considered to be equivalent. By comparing the probability distribution of the center-to-center distances for untethered and cross-linked versions, we are able to calculate the loss of translational entropy upon cross-linking. The distribution function for the untethered helices is calculated from the probability that a given helix is closer to its partner than to all other helices, the "Nearest Neighbor" method. This method requires no assumptions about the nature of the solvent, and hence resolves difficulties normally associated with calculations for systems in liquids. Analysis of the restriction of angular freedom upon tethering indicates that the loss of rotational entropy is negligible. The method is applied in the context of the folding of a ten turn helical coiled coil with the tether modeled as a Gaussian chain or a flexible amino acid chain. After correcting for loop closure entropy in the docked state, we estimate the introduction of a six-residue tether in the coiled coil results in an effective concentration of the chain to be about 4 or 100 mM, depending upon whether the helices are denatured or pre-folded prior to their association. Thus, tethering results in significant stabilization for systems with millimolar or stronger dissociation constants. Copyright 2002 Wiley-Liss, Inc.

Optimized 31P MRS in the human brain at 7 T with a dedicated RF coil setup

PubMed Central

van de Bank, Bart L.; Orzada, Stephan; Smits, Frits; Lagemaat, Miriam W.; Rodgers, Christopher T.; Bitz, Andreas K.

2015-01-01

The design and construction of a dedicated RF coil setup for human brain imaging (1H) and spectroscopy (31P) at ultra‐high magnetic field strength (7 T) is presented. The setup is optimized for signal handling at the resonance frequencies for 1H (297.2 MHz) and 31P (120.3 MHz). It consists of an eight‐channel 1H transmit–receive head coil with multi‐transmit capabilities, and an insertable, actively detunable 31P birdcage (transmit–receive and transmit only), which can be combined with a seven‐channel receive‐only 31P array. The setup enables anatomical imaging and 31P studies without removal of the coil or the patient. By separating transmit and receive channels and by optimized addition of array signals with whitened singular value decomposition we can obtain a sevenfold increase in SNR of 31P signals in the occipital lobe of the human brain compared with the birdcage alone. These signals can be further enhanced by 30 ± 9% using the nuclear Overhauser effect by B 1‐shimmed low‐power irradiation of water protons. Together, these features enable acquisition of 31P MRSI at high spatial resolutions (3.0 cm3 voxel) in the occipital lobe of the human brain in clinically acceptable scan times (~15 min). © 2015 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd. PMID:26492089

FPGA-based RF interference reduction techniques for simultaneous PET–MRI

PubMed Central

Gebhardt, P; Wehner, J; Weissler, B; Botnar, R; Marsden, P K; Schulz, V

2016-01-01

Abstract The combination of positron emission tomography (PET) and magnetic resonance imaging (MRI) as a multi-modal imaging technique is considered very promising and powerful with regard to in vivo disease progression examination, therapy response monitoring and drug development. However, PET–MRI system design enabling simultaneous operation with unaffected intrinsic performance of both modalities is challenging. As one of the major issues, both the PET detectors and the MRI radio-frequency (RF) subsystem are exposed to electromagnetic (EM) interference, which may lead to PET and MRI signal-to-noise ratio (SNR) deteriorations. Early digitization of electronic PET signals within the MRI bore helps to preserve PET SNR, but occurs at the expense of increased amount of PET electronics inside the MRI and associated RF field emissions. This raises the likelihood of PET-related MRI interference by coupling into the MRI RF coil unwanted spurious signals considered as RF noise, as it degrades MRI SNR and results in MR image artefacts. RF shielding of PET detectors is a commonly used technique to reduce PET-related RF interferences, but can introduce eddy-current-related MRI disturbances and hinder the highest system integration. In this paper, we present RF interference reduction methods which rely on EM field coupling–decoupling principles of RF receive coils rather than suppressing emitted fields. By modifying clock frequencies and changing clock phase relations of digital circuits, the resulting RF field emission is optimised with regard to a lower field coupling into the MRI RF coil, thereby increasing the RF silence of PET detectors. Our methods are demonstrated by performing FPGA-based clock frequency and phase shifting of digital silicon photo-multipliers (dSiPMs) used in the PET modules of our MR-compatible Hyperion IID PET insert. We present simulations and magnetic-field map scans visualising the impact of altered clock phase pattern on the spatial RF field distribution, followed by MRI noise and SNR scans performed with an operating PET module using different clock frequencies and phase patterns. The methods were implemented via firmware design changes without any hardware modifications. This introduces new means of flexibility by enabling adaptive RF interference reduction optimisations in the field, e.g. when using a PET insert with different MRI systems or when different MRI RF coil types are to be operated with the same PET detector. PMID:27049898

FPGA-based RF interference reduction techniques for simultaneous PET-MRI.

PubMed

Gebhardt, P; Wehner, J; Weissler, B; Botnar, R; Marsden, P K; Schulz, V

2016-05-07

The combination of positron emission tomography (PET) and magnetic resonance imaging (MRI) as a multi-modal imaging technique is considered very promising and powerful with regard to in vivo disease progression examination, therapy response monitoring and drug development. However, PET-MRI system design enabling simultaneous operation with unaffected intrinsic performance of both modalities is challenging. As one of the major issues, both the PET detectors and the MRI radio-frequency (RF) subsystem are exposed to electromagnetic (EM) interference, which may lead to PET and MRI signal-to-noise ratio (SNR) deteriorations. Early digitization of electronic PET signals within the MRI bore helps to preserve PET SNR, but occurs at the expense of increased amount of PET electronics inside the MRI and associated RF field emissions. This raises the likelihood of PET-related MRI interference by coupling into the MRI RF coil unwanted spurious signals considered as RF noise, as it degrades MRI SNR and results in MR image artefacts. RF shielding of PET detectors is a commonly used technique to reduce PET-related RF interferences, but can introduce eddy-current-related MRI disturbances and hinder the highest system integration. In this paper, we present RF interference reduction methods which rely on EM field coupling-decoupling principles of RF receive coils rather than suppressing emitted fields. By modifying clock frequencies and changing clock phase relations of digital circuits, the resulting RF field emission is optimised with regard to a lower field coupling into the MRI RF coil, thereby increasing the RF silence of PET detectors. Our methods are demonstrated by performing FPGA-based clock frequency and phase shifting of digital silicon photo-multipliers (dSiPMs) used in the PET modules of our MR-compatible Hyperion II (D) PET insert. We present simulations and magnetic-field map scans visualising the impact of altered clock phase pattern on the spatial RF field distribution, followed by MRI noise and SNR scans performed with an operating PET module using different clock frequencies and phase patterns. The methods were implemented via firmware design changes without any hardware modifications. This introduces new means of flexibility by enabling adaptive RF interference reduction optimisations in the field, e.g. when using a PET insert with different MRI systems or when different MRI RF coil types are to be operated with the same PET detector.

WE-G-17A-05: Real-Time Catheter Localization Using An Active MR Tracker for Interstitial Brachytherapy

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

Wang, W; Damato, A; Viswanathan, A

2014-06-15

Purpose: To develop a novel active MR-tracking system which can provide accurate and rapid localization of brachytherapy catheters, and assess its reliability and spatial accuracy in comparison to standard catheter digitization using MR images. Methods: An active MR tracker for brachytherapy was constructed by adding three printed-circuit micro-coils to the shaft of a commercial metallic stylet. A gel phantom with an embedded framework was built, into which fifteen 14-Gauge catheters were placed, following either with parallel or crossed paths. The tracker was inserted sequentially into each catheter, with MR-tracking running continuously. Tracking was also performed during the tracker's removal frommore » each catheter. Catheter trajectories measured from the insertion and the removal procedures using the same micro-coil were compared, as well as trajectories obtained using different micro-coils. A 3D high-resolution MR image dataset of the phantom was acquired and imported into a treatment planning system (TPS) for catheter digitization. A comparison between MR-tracked positions and positions digitized from MR images by TPS was performed. Results: The MR tracking shows good consistency for varying catheter paths and for all micro-coils (mean difference ∼1.1 mm). The average distance between the MR-tracking trajectory and catheter digitization from the MR images was 1.1 mm. Ambiguity in catheter assignment from images due to crossed paths was resolved by active tracking. When tracking was interleaved with imaging, real-time images were continuously acquired at the instantaneous tip positions and displayed on an external workstation. Conclusion: The active MR tracker may be used to provide an independent measurement of catheter location in the MR environment, potentially eliminating the need for subsequent CT. It may also be used to control realtime imaging of catheter placement. This will enable MR-based brachytherapy planning of interstitial implants without ionizing radiation, with the potential to enable dosimetric guidance of catheter placement. We gratefully acknowledge support from the American Heart Association SDG 10SDG2610139, NIH 1R21CA158987-01A1, U41-RR019703, and R21 CA 167800, as well as a BWH Department of Radiation Oncology post-doctoral fellowship support. Li Pan and Wesley Gilson are employees of Siemens Corporation, Corporate Technology. Ravi Seethamraju is an employee of Siemens Healthcare.« less

FPGA-based RF interference reduction techniques for simultaneous PET-MRI

NASA Astrophysics Data System (ADS)

Gebhardt, P.; Wehner, J.; Weissler, B.; Botnar, R.; Marsden, P. K.; Schulz, V.

2016-05-01

The combination of positron emission tomography (PET) and magnetic resonance imaging (MRI) as a multi-modal imaging technique is considered very promising and powerful with regard to in vivo disease progression examination, therapy response monitoring and drug development. However, PET-MRI system design enabling simultaneous operation with unaffected intrinsic performance of both modalities is challenging. As one of the major issues, both the PET detectors and the MRI radio-frequency (RF) subsystem are exposed to electromagnetic (EM) interference, which may lead to PET and MRI signal-to-noise ratio (SNR) deteriorations. Early digitization of electronic PET signals within the MRI bore helps to preserve PET SNR, but occurs at the expense of increased amount of PET electronics inside the MRI and associated RF field emissions. This raises the likelihood of PET-related MRI interference by coupling into the MRI RF coil unwanted spurious signals considered as RF noise, as it degrades MRI SNR and results in MR image artefacts. RF shielding of PET detectors is a commonly used technique to reduce PET-related RF interferences, but can introduce eddy-current-related MRI disturbances and hinder the highest system integration. In this paper, we present RF interference reduction methods which rely on EM field coupling-decoupling principles of RF receive coils rather than suppressing emitted fields. By modifying clock frequencies and changing clock phase relations of digital circuits, the resulting RF field emission is optimised with regard to a lower field coupling into the MRI RF coil, thereby increasing the RF silence of PET detectors. Our methods are demonstrated by performing FPGA-based clock frequency and phase shifting of digital silicon photo-multipliers (dSiPMs) used in the PET modules of our MR-compatible Hyperion II D PET insert. We present simulations and magnetic-field map scans visualising the impact of altered clock phase pattern on the spatial RF field distribution, followed by MRI noise and SNR scans performed with an operating PET module using different clock frequencies and phase patterns. The methods were implemented via firmware design changes without any hardware modifications. This introduces new means of flexibility by enabling adaptive RF interference reduction optimisations in the field, e.g. when using a PET insert with different MRI systems or when different MRI RF coil types are to be operated with the same PET detector.

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.

QSAR-Driven Design and Discovery of Novel Compounds With Antiplasmodial and Transmission Blocking Activities.

PubMed

Lima, Marilia N N; Melo-Filho, Cleber C; Cassiano, Gustavo C; Neves, Bruno J; Alves, Vinicius M; Braga, Rodolpho C; Cravo, Pedro V L; Muratov, Eugene N; Calit, Juliana; Bargieri, Daniel Y; Costa, Fabio T M; Andrade, Carolina H

2018-01-01

Malaria is a life-threatening infectious disease caused by parasites of the genus Plasmodium , affecting more than 200 million people worldwide every year and leading to about a half million deaths. Malaria parasites of humans have evolved resistance to all current antimalarial drugs, urging for the discovery of new effective compounds. Given that the inhibition of deoxyuridine triphosphatase of Plasmodium falciparum ( Pf dUTPase) induces wrong insertions in plasmodial DNA and consequently leading the parasite to death, this enzyme is considered an attractive antimalarial drug target. Using a combi-QSAR (quantitative structure-activity relationship) approach followed by virtual screening and in vitro experimental evaluation, we report herein the discovery of novel chemical scaffolds with in vitro potency against asexual blood stages of both P. falciparum multidrug-resistant and sensitive strains and against sporogonic development of P. berghei . We developed 2D- and 3D-QSAR models using a series of nucleosides reported in the literature as Pf dUTPase inhibitors. The best models were combined in a consensus approach and used for virtual screening of the ChemBridge database, leading to the identification of five new virtual Pf dUTPase inhibitors. Further in vitro testing on P. falciparum multidrug-resistant (W2) and sensitive (3D7) parasites showed that compounds LabMol-144 and LabMol-146 demonstrated fair activity against both strains and presented good selectivity versus mammalian cells. In addition, LabMol-144 showed good in vitro inhibition of P. berghei ookinete formation, demonstrating that hit-to-lead optimization based on this compound may also lead to new antimalarials with transmission blocking activity.

Activation patterns of Purkinje fibers during long-duration ventricular fibrillation in an isolated canine heart model.

PubMed

Tabereaux, Paul B; Walcott, Greg P; Rogers, Jack M; Kim, Jong; Dosdall, Derek J; Robertson, Peter G; Killingsworth, Cheryl R; Smith, William M; Ideker, Raymond E

2007-09-04

The roles of Purkinje fibers (PFs) and focal wave fronts, if any, in the maintenance of ventricular fibrillation (VF) are unknown. If PFs are involved in VF maintenance, it should be possible to map wave fronts propagating from PFs into the working ventricular myocardium during VF. If wave fronts ever arise focally during VF, it should be possible to map them appearing de novo. Six canine hearts were isolated, and the left main coronary artery was cannulated and perfused. The left ventricular cavity was exposed, which allowed direct endocardial mapping of the anterior papillary muscle insertion. Nonperfused VF was induced, and 6 segments of data, each 5 seconds long, were analyzed during 10 minutes of VF. During 36 segments of data that were analyzed, 1018 PF or focal wave fronts of activation were identified. In 534 wave fronts, activation was mapped propagating from working ventricular myocardium to PF. In 142 wave fronts, activation was mapped propagating from PF to working ventricular myocardium. In 342 wave fronts, activation was mapped arising focally. More than 1 of these 3 patterns could occur in the same wave front. PFs are highly active throughout the first 10 minutes of VF. In addition to retrograde propagation from the working ventricular myocardium to PFs, antegrade propagation occurs from PFs to working ventricular myocardium, which suggests PFs are important in VF maintenance. Prior plunge needle recordings in dogs indicate activation propagates from the endocardium toward the epicardium after 1 minute of VF, which suggests that focal sites on the endocardium may represent foci and not breakthrough. If so, in addition to reentry, abnormal automaticity or triggered activity may also occur during VF.

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.

Exploring the atomic structure and conformational flexibility of a 320 Å long engineered viral fiber using X-ray crystallography

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

Bhardwaj, Anshul; Casjens, Sherwood R.; Cingolani, Gino, E-mail: gino.cingolani@jefferson.edu

2014-02-01

This study presents the crystal structure of a ∼320 Å long protein fiber generated by in-frame extension of its repeated helical coiled-coil core. Protein fibers are widespread in nature, but only a limited number of high-resolution structures have been determined experimentally. Unlike globular proteins, fibers are usually recalcitrant to form three-dimensional crystals, preventing single-crystal X-ray diffraction analysis. In the absence of three-dimensional crystals, X-ray fiber diffraction is a powerful tool to determine the internal symmetry of a fiber, but it rarely yields atomic resolution structural information on complex protein fibers. An 85-residue-long minimal coiled-coil repeat unit (MiCRU) was previously identifiedmore » in the trimeric helical core of tail needle gp26, a fibrous protein emanating from the tail apparatus of the bacteriophage P22 virion. Here, evidence is provided that an MiCRU can be inserted in frame inside the gp26 helical core to generate a rationally extended fiber (gp26-2M) which, like gp26, retains a trimeric quaternary structure in solution. The 2.7 Å resolution crystal structure of this engineered fiber, which measures ∼320 Å in length and is only 20–35 Å wide, was determined. This structure, the longest for a trimeric protein fiber to be determined to such a high resolution, reveals the architecture of 22 consecutive trimerization heptads and provides a framework to decipher the structural determinants for protein fiber assembly, stability and flexibility.« less

A new video laryngo-pharyngoscope with shape-holding coiled tube and surgical forceps: a preliminary study.

PubMed

Tamura, Koichi; Kim, Masanobu; Abe, Koji; Toda, Naoki; Jinouchi, Osamu; Kalubi, Bukasa; Takeda, Noriaki

2009-12-01

We developed a new video laryngo-pharyngoscope with a shape-holding coiled tube and examined its effectiveness in some patients. The video laryngo-pharyngoscope is designed to inspect the pharynx and larynx transorally and to perform surgical manipulations. The scope consists of a coiled tube, a grip with trigger connected to the forceps and a CCD Camera with a battery. The stainless coiled tube of the scope is flexible but shape-holding, so that its shape can be changed by hand with the characteristic that the new orientation remains invariable during both inspection and operation in the pharynx and larynx. After a local anesthesia, the operator holds the scope in one hand and pulls the patient's tongue by the other hand. The operator then inserted the scope transorally while monitoring video images that were wirelessly transferred to the display to ensure that the forceps has reached the area of interest and treated lesions successfully. Using the scope, we successfully examined the upper airway lesions and removed foreign bodies from the pharynx and performed both resection of a benign tumor and taking a biopsy of a malignant tumor from the pharynx and larynx. But, we could hardly remove vocal fold polyps because of the structural limitation of the scope. We demonstrated that the new video laryngo-pharyngoscope can be used safely and successfully in the inspection and removal of lesions in the oropharynx and supraglottic area of the larynx and will be a useful tool for minimally invasive office-based surgery.

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

3D Magnetic field modeling of a new superconducting synchronous machine using reluctance network method

NASA Astrophysics Data System (ADS)

Kelouaz, Moussa; Ouazir, Youcef; Hadjout, Larbi; Mezani, Smail; Lubin, Thiery; Berger, Kévin; Lévêque, Jean

2018-05-01

In this paper a new superconducting inductor topology intended for synchronous machine is presented. The studied machine has a standard 3-phase armature and a new kind of 2-poles inductor (claw-pole structure) excited by two coaxial superconducting coils. The air-gap spatial variation of the radial flux density is obtained by inserting a superconducting bulk, which deviates the magnetic field due to the coils. The complex geometry of this inductor usually needs 3D finite elements (FEM) for its analysis. However, to avoid a long computational time inherent to 3D FEM, we propose in this work an alternative modeling, which uses a 3D meshed reluctance network. The results obtained with the developed model are compared to 3D FEM computations as well as to measurements carried out on a laboratory prototype. Finally, a 3D FEM study of the shielding properties of the superconducting screen demonstrates the suitability of using a diamagnetic-like model of the superconducting screen.

Superconducting shielded core reactor with reduced AC losses

DOEpatents

Cha, Yung S.; Hull, John R.

2006-04-04

A superconducting shielded core reactor (SSCR) operates as a passive device for limiting excessive AC current in a circuit operating at a high power level under a fault condition such as shorting. The SSCR includes a ferromagnetic core which may be either closed or open (with an air gap) and extends into and through a superconducting tube or superconducting rings arranged in a stacked array. First and second series connected copper coils each disposed about a portion of the iron core are connected to the circuit to be protected and are respectively wound inside and outside of the superconducting tube or rings. A large impedance is inserted into the circuit by the core when the shielding capability of the superconducting arrangement is exceeded by the applied magnetic field generated by the two coils under a fault condition to limit the AC current in the circuit. The proposed SSCR also affords reduced AC loss compared to conventional SSCRs under continuous normal operation.

Catheter-based flexible microcoil RF detectors for internal magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Ahmad, M. M.; Syms, R. R. A.; Young, I. R.; Mathew, B.; Casperz, W.; Taylor-Robinson, S. D.; Wadsworth, C. A.; Gedroyc, W. M. W.

2009-07-01

Flexible catheter probes for magnetic resonance imaging (MRI) of the bile duct are demonstrated. The probes consist of a cytology brush modified to accept a resonant RF detector based on a spiral microcoil and hybrid integrated capacitors, and are designed for insertion into the duct via a non-magnetic endoscope during endoscopic retrograde cholangiopancreatography (ERCP). The coil must be narrow enough (<3 mm) to pass through the biopsy channel of the endoscope and sufficiently flexible to turn through 90° to enter the duct. Coils are fabricated as multi-turn electroplated conductors on a flexible base, and two designs formed on SU-8 and polyimide substrates are compared. It is shown that careful control of thermal load is used to obtain useable mechanical properties from SU-8, and that polyimide/SU-8 composites offer improved mechanical reliability. Good electrical performance is demonstrated and sub-millimetre resolution is obtained in 1H MRI experiments at 1.5 T magnetic field strength using test phantoms and in vitro liver tissue.

The structure of FMNL2-Cdc42 yields insights into the mechanism of lamellipodia and filopodia formation

NASA Astrophysics Data System (ADS)

Kühn, Sonja; Erdmann, Constanze; Kage, Frieda; Block, Jennifer; Schwenkmezger, Lisa; Steffen, Anika; Rottner, Klemens; Geyer, Matthias

2015-05-01

Formins are actin polymerization factors that elongate unbranched actin filaments at the barbed end. Rho family GTPases activate Diaphanous-related formins through the relief of an autoregulatory interaction. The crystal structures of the N-terminal domains of human FMNL1 and FMNL2 in complex with active Cdc42 show that Cdc42 mediates contacts with all five armadillo repeats of the formin with specific interactions formed by the Rho-GTPase insert helix. Mutation of three residues within Rac1 results in a gain-of-function mutation for FMNL2 binding and reconstitution of the Cdc42 phenotype in vivo. Dimerization of FMNL1 through a parallel coiled coil segment leads to formation of an umbrella-shaped structure that--together with Cdc42--spans more than 15 nm in diameter. The two interacting FMNL-Cdc42 heterodimers expose six membrane interaction motifs on a convex protein surface, the assembly of which may facilitate actin filament elongation at the leading edge of lamellipodia and filopodia.

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

Detection of Membrane Puncture with Haptic Feedback using a Tip-Force Sensing Needle.

PubMed

Elayaperumal, Santhi; Bae, Jung Hwa; Daniel, Bruce L; Cutkosky, Mark R

2014-09-01

This paper presents calibration and user test results of a 3-D tip-force sensing needle with haptic feedback. The needle is a modified MRI-compatible biopsy needle with embedded fiber Bragg grating (FBG) sensors for strain detection. After calibration, the needle is interrogated at 2 kHz, and dynamic forces are displayed remotely with a voice coil actuator. The needle is tested in a single-axis master/slave system, with the voice coil haptic display at the master, and the needle at the slave end. Tissue phantoms with embedded membranes were used to determine the ability of the tip-force sensors to provide real-time haptic feedback as compared to external sensors at the needle base during needle insertion via the master/slave system. Subjects were able to determine the position of the embedded membranes with significantly better accuracy using FBG tip feedback than with base feedback using a commercial force/torque sensor (p = 0.045) or with no added haptic feedback (p = 0.0024).

Detection of Membrane Puncture with Haptic Feedback using a Tip-Force Sensing Needle

PubMed Central

Elayaperumal, Santhi; Bae, Jung Hwa; Daniel, Bruce L.; Cutkosky, Mark R.

2015-01-01

This paper presents calibration and user test results of a 3-D tip-force sensing needle with haptic feedback. The needle is a modified MRI-compatible biopsy needle with embedded fiber Bragg grating (FBG) sensors for strain detection. After calibration, the needle is interrogated at 2 kHz, and dynamic forces are displayed remotely with a voice coil actuator. The needle is tested in a single-axis master/slave system, with the voice coil haptic display at the master, and the needle at the slave end. Tissue phantoms with embedded membranes were used to determine the ability of the tip-force sensors to provide real-time haptic feedback as compared to external sensors at the needle base during needle insertion via the master/slave system. Subjects were able to determine the position of the embedded membranes with significantly better accuracy using FBG tip feedback than with base feedback using a commercial force/torque sensor (p = 0.045) or with no added haptic feedback (p = 0.0024). PMID:26509101

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.

A structural model of polyglutamine determined from a host-guest method combining experiments and landscape theory.

PubMed

Finke, John M; Cheung, Margaret S; Onuchic, José N

2004-09-01

Modeling the structure of natively disordered peptides has proved difficult due to the lack of structural information on these peptides. In this work, we use a novel application of the host-guest method, combining folding theory with experiments, to model the structure of natively disordered polyglutamine peptides. Initially, a minimalist molecular model (C(alpha)C(beta)) of CI2 is developed with a structurally based potential and captures many of the folding properties of CI2 determined from experiments. Next, polyglutamine "guest" inserts of increasing length are introduced into the CI2 "host" model and the polyglutamine is modeled to match the resultant change in CI2 thermodynamic stability between simulations and experiments. The polyglutamine model that best mimics the experimental changes in CI2 thermodynamic stability has 1), a beta-strand dihedral preference and 2), an attractive energy between polyglutamine atoms 0.75-times the attractive energy between the CI2 host Go-contacts. When free-energy differences in the CI2 host-guest system are correctly modeled at varying lengths of polyglutamine guest inserts, the kinetic folding rates and structural perturbation of these CI2 insert mutants are also correctly captured in simulations without any additional parameter adjustment. In agreement with experiments, the residues showing structural perturbation are located in the immediate vicinity of the loop insert. The simulated polyglutamine loop insert predominantly adopts extended random coil conformations, a structural model consistent with low resolution experimental methods. The agreement between simulation and experimental CI2 folding rates, CI2 structural perturbation, and polyglutamine insert structure show that this host-guest method can select a physically realistic model for inserted polyglutamine. If other amyloid peptides can be inserted into stable protein hosts and the stabilities of these host-guest mutants determined, this novel host-guest method may prove useful to determine structural preferences of these intractable but biologically relevant protein fragments.

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.

1H, 13C, and 15N resonance assignments for the protein coded by gene locus BB0938 of Bordetella bronchiseptica

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

Rossi, Paolo; Ramelot, Theresa A.; Xiao, Rong

2005-11-01

The product of gene locus BB0938 from Bordetella bronchiseptica (Swiss-Prot ID: Q7WNU7-BORBR; NESG target ID: BoR11; Wunderlich et al., 2004; Pfam ID: PF03476) is a 128-residue protein of unknown function. This broadly conserved protein family is found in eubacteria and eukaryotes. Using triple resonance NMR techniques, we have determined 98% of backbone and 94% of side chain 1H, 13C, and 15N resonance assignments. The chemical shift and 3J(HN?Ha) scalar coupling data reveal a b topology with a seven-residue helical insert, ??????????. BMRB deposit with accession number 6693. Reference: Wunderlich et al. (2004) Proteins, 56, 181?187.

Lithium insertion in graphite from ternary ionic liquid-lithium salt electrolytes. I. Electrochemical characterization of the electrolytes

NASA Astrophysics Data System (ADS)

Appetecchi, Giovanni B.; Montanino, Maria; Balducci, Andrea; Lux, Simon F.; Winterb, Martin; Passerini, Stefano

In this paper we report the results of chemical-physical investigation performed on ternary room temperature ionic liquid-lithium salt mixtures as electrolytes for lithium-ion battery systems. The ternary electrolytes were made by mixing N-methyl- N-propyl pyrrolidinium bis(fluorosulfonyl) imide (PYR 13FSI) and N-butyl- N-methylpyrrolidinium bis(trifluoromethanesulfonyl) imide (PYR 14TFSI) ionic liquids with lithium hexafluorophosphate (LiPF 6) or lithium bis(trifluoromethanesulfonyl)imide (LiTFSI). The mixtures were developed based on preliminary results on the cyclability of graphite electrodes in the IL-LiX binary electrolytes. The results clearly show the beneficial synergic effect of the two ionic liquids on the electrochemical properties of the mixtures.

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.

Megagauss Fields during Milliseconds

NASA Astrophysics Data System (ADS)

Campbell, L. J.; Embury, D.; Han, K.; Parkin, D. M.; Baca, A. G.; Kihara, K. H.; Sims, J. R.; Boebinger, G.; Eyssa, Y.; Lesch, B.; Li, L.; Schillig, J.; Schneider-Muntau, H.; Walsh, R.

2004-11-01

A non-destructive, one megagauss magnet is now being designed in cooperation between the Los Alamos National Laboratory and the National High Magnetic Field Laboratory (NHMFL) through joint funding by the US Department of Energy and the US National Science Foundation. The design combines two types of pulsed magnet now in use at the NHMFL: a capacitor-driven `insert' magnet with a total pulse width of order 10 ms and a much larger `outsert' magnet with a total pulse width of order 2 seconds that is driven by a controlled power source. The insert and outsert produce approximately 1/2 megagauss each. Although the design uses CuAg as the principal conductor, further design efforts and materials development involve exploring CuNb and stainless steel-clad copper as possible future alternatives. A crucial innovation employed wound steel strip (sheet) as reinforcement in both insert and outsert coils. This gives extra strength due to the higher degree of cold-work possible in strip materials. A key role is played by materials development for this leading edge magnet. A major component, the 7-module, 560 MVA controlled dc power supply required for the outsert has been installed and commissioned.

Applications of Superconductivity and Impact on U.S. Economy

NASA Astrophysics Data System (ADS)

Selvamanickam, Venkat

2014-03-01

In the past few decades, low temperature superconducting wires (niobium-titanium) have enabled multibillion dollar industries such as magnetic resonance imaging and nuclear magnetic resonance spectroscopy which otherwise would not have been possible. High temperature superconductors (HTS) hold the promise of impacting even a larger market in diverse applications such as energy, health, military, telecommunication, transportation and research. HTS tapes are now being manufactured in quantities of few hundred kilometers annually with current carrying capacity of about 300 times that of copper wire of the same cross section. Power transmission cables up to few kilometers in length made with HTS tapes have already been inserted in the power grid world-wide. In the past few of years, tremendous advancements have occurred in nanoscale defect engineering in these thin film superconducting tapes that has led to a doubling of critical current performance in high magnetic fields and operating temperatures of interest for various applications. Technologies developed in this area have been successfully inserted in production HTS tapes by industry. With the availability of such high performance HTS tapes, a number of coil-based applications are now being aggressively pursued by several institutions. HTS coils enable power devices with high power density with significant weight, size and power benefits. Energy storage, generation, use, transformation and transmission applications as well as magnetic applications such as magnetic shields, plasma confinement, and ultra-high field magnets are becoming possible with the availability of high-performance HTS tapes. An overview of the development and use of superconductors in electric power and magnetic applications will be provided in this presentation.

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

In Vitro Measurement of Tissue Integrity during Saccular Aneurysm Embolizations for Simulator-Based Training

PubMed Central

Tercero, C.; Ikeda, S.; Ooe, K.; Fukuda, T.; Arai, F.; Negoro, M.; Takahashi, I.; Kwon, G.

2012-01-01

Summary In the domain of endovascular neurosurgery, the measurement of tissue integrity is needed for simulator-based training and for the development of new intravascular instruments and treatment techniques. In vitro evaluation of tissue manipulation can be achieved using photoelastic stress analysis and vasculature modeling with photoelastic materials. In this research we constructed two types of vasculature models of saccular aneurysms for differentiation of embolization techniques according to the respect for tissue integrity measurements based on the stress within the blood vessel model wall. In an aneurysm model with 5 mm dome diameter, embolization using MicroPlex 10 (Complex 1D, with 4 mm diameter loops), a maximum area of 3.97 mm2 with stress above 1 kPa was measured. This area increased to 5.50 mm2 when the dome was touched deliberately with the release mechanism of the coil, and to 4.87 mm2 for an embolization using Micrusphere, (Spherical 18 Platinum Coil). In a similar way trans-cell stent-assisted coil embolization was also compared to human blood pressure simulation using a model of a wide-necked saccular aneurysm with 7 mm diameter. The area with stress above 1kPa was below 1 mm2 for the pressure simulation and maximized at 3.79 mm2 during the trans-cell insertion of the micro-catheter and at 8.92 mm2 during the embolization. The presented results show that this measurement system is useful for identifying techniques compromising tissue integrity, comparing and studying coils and embolization techniques for a specific vasculature morphology and comparing their natural stress variations such as that produced by blood pressure. PMID:23217635

Performance analysis of Rogowski coils and the measurement of the total toroidal current in the ITER machine

NASA Astrophysics Data System (ADS)

Quercia, A.; Albanese, R.; Fresa, R.; Minucci, S.; Arshad, S.; Vayakis, G.

2017-12-01

The paper carries out a comprehensive study of the performances of Rogowski coils. It describes methodologies that were developed in order to assess the capabilities of the Continuous External Rogowski (CER), which measures the total toroidal current in the ITER machine. Even though the paper mainly considers the CER, the contents are general and relevant to any Rogowski sensor. The CER consists of two concentric helical coils which are wound along a complex closed path. Modelling and computational activities were performed to quantify the measurement errors, taking detailed account of the ITER environment. The geometrical complexity of the sensor is accurately accounted for and the standard model which provides the classical expression to compute the flux linkage of Rogowski sensors is quantitatively validated. Then, in order to take into account the non-ideality of the winding, a generalized expression, formally analogue to the classical one, is presented. Models to determine the worst case and the statistical measurement accuracies are hence provided. The following sources of error are considered: effect of the joints, disturbances due to external sources of field (the currents flowing in the poloidal field coils and the ferromagnetic inserts of ITER), deviations from ideal geometry, toroidal field variations, calibration, noise and integration drift. The proposed methods are applied to the measurement error of the CER, in particular in its high and low operating ranges, as prescribed by the ITER system design description documents, and during transients, which highlight the large time constant related to the shielding of the vacuum vessel. The analyses presented in the paper show that the design of the CER diagnostic is capable of achieving the requisite performance as needed for the operation of the ITER machine.

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.

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.

Characterization and dioxygen reactivity of a new series of coordinatively unsaturated thiolate-ligated manganese(II) complexes.

PubMed

Coggins, Michael K; Toledo, Santiago; Shaffer, Erika; Kaminsky, Werner; Shearer, Jason; Kovacs, Julie A

2012-06-18

The synthesis, structural, and spectroscopic characterization of four new coordinatively unsaturated mononuclear thiolate-ligated manganese(II) complexes ([Mn(II)(S(Me2)N(4)(6-Me-DPEN))](BF(4)) (1), [Mn(II)(S(Me2)N(4)(6-Me-DPPN))](BPh(4))·MeCN (3), [Mn(II)(S(Me2)N(4)(2-QuinoPN))](PF(6))·MeCN·Et(2)O (4), and [Mn(II)(S(Me2)N(4)(6-H-DPEN)(MeOH)](BPh(4)) (5)) is described, along with their magnetic, redox, and reactivity properties. These complexes are structurally related to recently reported [Mn(II)(S(Me2)N(4)(2-QuinoEN))](PF(6)) (2) (Coggins, M. K.; Kovacs, J. A. J. Am. Chem. Soc.2011, 133, 12470). Dioxygen addition to complexes 1-5 is shown to result in the formation of five new rare examples of Mn(III) dimers containing a single, unsupported oxo bridge: [Mn(III)(S(Me2)N(4)(6-Me-DPEN)](2)-(μ-O)(BF(4))(2)·2MeOH (6), [Mn(III)(S(Me2)N(4)(QuinoEN)](2)-(μ-O)(PF(6))(2)·Et(2)O (7), [Mn(III)(S(Me2)N(4)(6-Me-DPPN)](2)-(μ-O)(BPh(4))(2) (8), [Mn(III)(S(Me2)N(4)(QuinoPN)](2)-(μ-O)(BPh(4))(2) (9), and [Mn(III)(S(Me2)N(4)(6-H-DPEN)](2)-(μ-O)(PF(6))(2)·2MeCN (10). Labeling studies show that the oxo atom is derived from (18)O(2). Ligand modifications, involving either the insertion of a methylene into the backbone or the placement of an ortho substituent on the N-heterocyclic amine, are shown to noticeably modulate the magnetic and reactivity properties. Fits to solid-state magnetic susceptibility data show that the Mn(III) ions of μ-oxo dimers 6-10 are moderately antiferromagnetically coupled, with coupling constants (2J) that fall within the expected range. Metastable intermediates, which ultimately convert to μ-oxo bridged 6 and 7, are observed in low-temperature reactions between 1 and 2 and dioxygen. Complexes 3-5, on the other hand, do not form observable intermediates, thus illustrating the effect that relatively minor ligand modifications have upon the stability of metastable dioxygen-derived species.

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.

Characterization of a Chlamydomonas Insertional Mutant that Disrupts Flagellar Central Pair Microtubule-associated Structures

PubMed Central

Mitchell, David R.; Sale, Winfield S.

1999-01-01

Two alleles at a new locus, central pair–associated complex 1 (CPC1), were selected in a screen for Chlamydomonas flagellar motility mutations. These mutations disrupt structures associated with central pair microtubules and reduce flagellar beat frequency, but do not prevent changes in flagellar activity associated with either photophobic responses or phototactic accumulation of live cells. Comparison of cpc1 and pf6 axonemes shows that cpc1 affects a row of projections along C1 microtubules distinct from those missing in pf6, and a row of thin fibers that form an arc between the two central pair microtubules. Electron microscopic images of the central pair in axonemes from radial spoke–defective strains reveal previously undescribed central pair structures, including projections extending laterally toward radial spoke heads, and a diagonal link between the C2 microtubule and the cpc1 projection. By SDS-PAGE, cpc1 axonemes show reductions of 350-, 265-, and 79-kD proteins. When extracted from wild-type axonemes, these three proteins cosediment on sucrose gradients with three other central pair proteins (135, 125, and 56 kD) in a 16S complex. Characterization of cpc1 provides new insights into the structure and biochemistry of the central pair apparatus, and into its function as a regulator of dynein-based motility. PMID:9922455

Cleavage of precursors by the mitochondrial processing peptidase requires a compatible mature protein or an intermediate octapeptide

PubMed Central

1991-01-01

Many precursors of mitochondrial proteins are processed in two successive steps by independent matrix peptidases (MPP and MIP), whereas others are cleaved in a single step by MPP alone. To explain this dichotomy, we have constructed deletions of all or part of the octapeptide characteristic of a twice cleaved precursor (human ornithine transcarbamylase [pOTC]), have exchanged leader peptide sequences between once-cleaved (human methylmalonyl-CoA mutase [pMUT]; yeast F1ATPase beta-subunit [pF1 beta]) and twice-cleaved (pOTC; rat malate dehydrogenase (pMDH); Neurospora ubiquinol-cytochrome c reductase iron-sulfur subunit [pFe/S]) precursors, and have incubated these proteins with purified MPP and MIP. When the octapeptide of pOTC was deleted, or when the entire leader peptide of a once-cleaved precursor (pMUT or pF1 beta) was joined to the mature amino terminus of a twice-cleaved precursor (pOTC or pFe/S), no cleavage was produced by either protease. Cleavage of these constructs by MPP was restored by re- inserting as few as two amino-terminal residues of the octapeptide or of the mature amino terminus of a once-cleaved precursor. We conclude that the mature amino terminus of a twice-cleaved precursor is structurally incompatible with cleavage by MPP; such proteins have evolved octapeptides cleaved by MIP to overcome this incompatibility. PMID:1672532

Molecular cloning, characterization and comparison of bile salt hydrolases from Lactobacillus johnsonii PF01.

PubMed

Chae, J P; Valeriano, V D; Kim, G-B; Kang, D-K

2013-01-01

To clone, characterize and compare the bile salt hydrolase (BSH) genes of Lactobacillus johnsonii PF01. The BSH genes were amplified by polymerase chain reaction (PCR) using specific oligonucleotide primers, and the products were inserted into the pET21b expression vector. Escherichia coli BLR (DE3) cells were transformed with pET21b vectors containing the BSH genes and induced using 0·1 mmol l(-1) isopropylthiolgalactopyranoside. The overexpressed BSH enzymes were purified using a nickel-nitrilotriacetic acid (Ni(2+) -NTA) agarose column and their activities characterized. BSH A hydrolysed tauro-conjugated bile salts optimally at pH 5·0 and 55°C, whereas BSH C hydrolysed glyco-conjugated bile salts optimally at pH 5·0 and 70°C. The enzymes had no preferential activities towards a specific cholyl moiety. BSH enzymes vary in their substrate specificities and characteristics to broaden its activity. Despite the lack of conservation in their putative substrate-binding sites, these remain functional through motif conservation. This is to our knowledge the first report of isolation of BSH enzymes from a single strain, showing hydrolase activity towards either glyco-conjugated or tauro-conjugated bile salts. Future structural homology studies and site-directed mutagenesis of sites associated with substrate specificity may elucidate specificities of BSH enzymes. © 2012 The Society for Applied Microbiology.

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

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

Material and cooling requirements for poly-Bitter resistive magnets and hybrid inserts generating continuous fields up to 50 T

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

Gao, B.J.; Bird, M.D.; Eyssa, Y.M.

1994-07-01

The new National High Magnetic Field Laboratory (NHMFL), equipped with a 40 MW DC power supply, will design and construct the next generation of high field resistive magnets and hybrid inserts generating DC fields up to 50 T. The authors present a study on the required materials and the necessary cooling characteristics, these magnets need. The configuration selected for this study consists of a combination of thin poly-Bitter and thick Bitter coils optimized in dimensions and power under constraint of maximum design stress and heat removal to obtain maximum field. The study shows that each design requires a different optimummore » ratio of conductor strength to electrical conductivity and that efficient cooling is only advantageous if strong copper alloys are used. For efficient use of the available power the development of new high strength, high conductivity materials will be necessary. Equally important are improvements in the heat transfer characteristics of these high power density magnets.« less

R1 dispersion contrast at high field with fast field-cycling MRI

NASA Astrophysics Data System (ADS)

Bödenler, Markus; Basini, Martina; Casula, Maria Francesca; Umut, Evrim; Gösweiner, Christian; Petrovic, Andreas; Kruk, Danuta; Scharfetter, Hermann

2018-05-01

Contrast agents with a strong R1 dispersion have been shown to be effective in generating target-specific contrast in MRI. The utilization of this R1 field dependence requires the adaptation of an MRI scanner for fast field-cycling (FFC). Here, we present the first implementation and validation of FFC-MRI at a clinical field strength of 3 T. A field-cycling range of ±100 mT around the nominal B0 field was realized by inserting an additional insert coil into an otherwise conventional MRI system. System validation was successfully performed with selected iron oxide magnetic nanoparticles and comparison to FFC-NMR relaxometry measurements. Furthermore, we show proof-of-principle R1 dispersion imaging and demonstrate the capability of generating R1 dispersion contrast at high field with suppressed background signal. With the presented ready-to-use hardware setup it is possible to investigate MRI contrast agents with a strong R1 dispersion at a field strength of 3 T.

Synthesis and evaluation of thermo-rheological behaviour and ionotropic crosslinking of new gellan gum-alkyl derivatives.

PubMed

Agnello, Stefano; Palumbo, Fabio Salvatore; Pitarresi, Giovanna; Fiorica, Calogero; Giammona, Gaetano

2018-04-01

This paper reports the synthesis and the physicochemical characterization of two series of gellan gum (GG) derivatives functionalized with alkyl chains with different number of carbon, from 8 to 18. In particular, low molecular weight gellan gum samples with 52.6 or 96.7 kDa, respectively, were functionalized with octylamine (C 8 ), dodecylamine (C 12 ) and octadecylamine (C 18 ) by using bis(4-nitrophenyl) carbonate (4-NPBC) as a coupling agent. Thermo-rheological and ionotropic crosslinking properties of these gellan gum-alkyl derivatives were evaluated and related to the degree of derivatization in alkyl chains. Results suggested as length and degree of derivatization differently influenced coil-to-helix gelation mechanism of GG derivatives, ionotropic crosslinking, and strength of crosslinked hydrogels obtained in CaCl 2 0.102 M and NaCl 0.15 M. Statement of hypothesis: The insertion of alkyl chains on the gellan gum backbone interferes with coil-to-helix transition mechanism and allows the production of hydrophobically assembled hydrogels. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

Organic solvents, electrolytes, and lithium ion cells with good low temperature performance

NASA Technical Reports Server (NTRS)

Huang, Chen-Kuo (Inventor); Smart, Marshall C. (Inventor); Surampudi, Subbarao (Inventor); Bugga, Ratnakumar V. (Inventor)

2002-01-01

Multi-component organic solvent systems, electrolytes and electrochemical cells characterized by good low temperature performance are provided. In one embodiment, an improved organic solvent system contains a ternary mixture of ethylene carbonate, dimethyl carbonate and diethyl carbonate. In other embodiments, quaternary systems include a fourth component, i.e, an aliphatic ester, an asymmetric alkyl carbonate or a compound of the formula LiOX, where X is R, COOR, or COR, where R is alkyl or fluoroalkyl. Electrolytes based on such organic solvent systems are also provided and contain therein a lithium salt of high ionic mobility, such as LiPF.sub.6. Reversible electrochemical cells, particularly lithium ion cells, are constructed with the improved electrolytes, and preferably include a carbonaceous anode, an insertion type cathode, and an electrolyte interspersed therebetween.

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.

Analysis of the ITER central solenoid insert (CSI) coil stability tests

NASA Astrophysics Data System (ADS)

Savoldi, L.; Bonifetto, R.; Breschi, M.; Isono, T.; Martovetsky, N.; Ozeki, H.; Zanino, R.

2017-07-01

At the end of the test campaign of the ITER Central Solenoid Insert (CSI) coil in 2015, after 16,000 electromagnetic (EM) cycles, some tests were devoted to the study of the conductor stability, through the measurement of the Minimum Quench Energy (MQE). The tests were performed by means of an inductive heater (IH), located in the high-field region of the CSI and wrapped around the conductor. The calorimetric calibration of the IH is presented here, aimed at assessing the energy deposited in the conductor for different values of the IH electrical operating conditions. The MQE of the conductor of the ITER CS module 3L can be estimated as ∼200 J ± 20%, deposited on the whole conductor on a length of ∼10 cm (the IH length) in ∼40 ms, at current and magnetic field conditions relevant for the ITER CS operation. The repartition of the energy deposited in the conductor under the IH is computed to be ∼10% in the cable and 90% in the jacket by means of a 3D Finite Elements EM model. It is shown how this repartition implies that the bundle (cable + helium) heat capacity is fully available for stability on the time scale of the tested disturbances. This repartition is used in input to the thermal-hydraulic analysis performed with the 4C code, to assess the capability of the model to accurately reproduce the stability threshold of the conductor. The MQE computed by the code for this disturbance is in good agreement with the measured value, with an underestimation within 15% of the experimental value.

Dystrophin Hot-Spot Mutants Leading to Becker Muscular Dystrophy Insert More Deeply into Membrane Models than the Native Protein.

PubMed

Ameziane-Le Hir, Sarah; Paboeuf, Gilles; Tascon, Christophe; Hubert, Jean-François; Le Rumeur, Elisabeth; Vié, Véronique; Raguénès-Nicol, Céline

2016-07-26

Dystrophin (DYS) is a membrane skeleton protein whose mutations lead to lethal Duchenne muscular dystrophy or to the milder Becker muscular dystrophy (BMD). One third of BMD "in-frame" exon deletions are located in the region that codes for spectrin-like repeats R16 to R21. We focused on four prevalent mutated proteins deleted in this area (called RΔ45-47, RΔ45-48, RΔ45-49, and RΔ45-51 according to the deleted exon numbers), analyzing protein/membrane interactions. Two of the mutants, RΔ45-48 and RΔ45-51, led to mild pathologies and displayed a similar triple coiled-coil structure as the full-length DYS R16-21, whereas the two others, RΔ45-47 and RΔ45-49, induced more severe pathologies and showed "fractional" structures unrelated to the normal one. To explore lipid packing, small unilamellar liposomes (SUVs) and planar monolayers were used at various initial surface pressures. The dissociation constants determined by microscale thermophoresis (MST) were much higher for the full-length DYS R161-21 than for the mutants; thus the wild type protein has weaker SUV binding. Comparing surface pressures after protein adsorption and analysis of atomic force microscopy images of mixed protein/lipid monolayers revealed that the mutants insert more into the lipid monolayer than the wild type does. In fact, in both models every deletion mutant showed more interactions with membranes than the full-length protein did. This means that mutations in the R16-21 part of dystrophin disturb the protein's molecular behavior as it relates to membranes, regardless of whether the accompanying pathology is mild or severe.

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.

Optimizing T2-weighted magnetic resonance sequences for surface coil microimaging of the eye with regard to lid, eyeball and head moving artifacts.

PubMed

Obata, Takayuki; Uemura, Koji; Nonaka, Hiroi; Tamura, Mitsuru; Tanada, Shuji; Ikehira, Hiroo

2006-01-01

To acquire high-resolution magnetic resonance (MR) images, we developed a new blinking artifact reduced pulse (BARP) sequence with a surface coil specialized for microscopic imaging (47 mm in diameter). To reduce eye movement, we ascertained that the subjects' eyes were kept open and fixated to the target in the 1.5-T MR gantry. To reduce motion artifacts from blinking, we inserted rest periods for blinking (1.5 s within every 5 s) during MR scanning (T2-weighted fast spin echo; repetition time, 5 s; echo time, 100 ms; echo train, 11; matrix, 256 x 128; field of view, 5 cm; 1-mm thickness x 30 slices). Three scans (100 s x 3) were performed for each normal subject, and they were added together after automatic adjustment for location to reduce quality loss caused by head motion. T2-weighted MR images were acquired with a high resolution and a high signal-to-noise ratio. Motion artifacts were reduced with BARP, as compared with those with random blinking. Intraocular structures such as the iris and ciliary muscles were clearly visualized. Because the whole eye can be covered with a 1-mm thickness by this method, three-dimensional maps can easily be generated from the obtained images. The application of BARP with a surface coil of the human eye might become a useful and widely adopted procedure for MR microimaging.

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.

Feasible voltage-tap based quench detection in a Ag/Bi-2212 coil enabled by fast 3D normal zone propagation

DOE PAGES

Shen, Tengming; Ye, Liyang; Li, Pei

2016-07-01

For this study, small insert solenoids have been built using a commercial Ag/Bi-2212 multifilamentary round wire, insulated with a new thin TiO 2– polymer coating insulation (thickness in ~20 μm versus ~100 μm for a commonly used mullite braided sleeve insulation), and characterized in background magnetic field up to 14 T at 4.2 K to explore the high-field performance and quench detection of Bi-2212 magnets. The coil has no visible leakage and no electrical shorts after reaction, and it carries 280 A/mm -2 in a background field 14 T and generates an additional 1.7 T. A notable result is that,more » despite normal zones propagate slowly along the conductor, the hot spot temperature upon detection increases only from 40 K to 60 K when the resistive quench detection voltage threshold increases from 0.1 V to 1 V for all operating current density investigated, showing that quench detection using voltage taps is feasible for this coil. This is in a strong contrast to a coil we previously built to the same specifications but from wires insulated with the mullite braided sleeve insulation, for which the hot spot temperature upon detection increases from ~80 K to ~140 K while increasing from the detection voltage threshold from 0.1 V to 1 V, and thus for which quench detection using voltage taps presents significant risks, consistent with the common belief that the effectiveness of quench detection using voltage taps for superconducting magnets built using high temperature superconductors is seriously compromised by their slow normal zone propagation. This striking difference is ascribed to the fast transverse quench propagation enabled by thin insulation and improved thermal coupling between conductor turns. Finally, this work demonstrates that quench detection for high-temperature superconducting magnets highly depends on the design and construction of the coils such as insulation materials used and this dependence should be factored into the overall magnet design.« less

Feasible voltage-tap based quench detection in a Ag/Bi-2212 coil enabled by fast 3D normal zone propagation

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

Shen, Tengming; Ye, Liyang; Li, Pei

For this study, small insert solenoids have been built using a commercial Ag/Bi-2212 multifilamentary round wire, insulated with a new thin TiO 2– polymer coating insulation (thickness in ~20 μm versus ~100 μm for a commonly used mullite braided sleeve insulation), and characterized in background magnetic field up to 14 T at 4.2 K to explore the high-field performance and quench detection of Bi-2212 magnets. The coil has no visible leakage and no electrical shorts after reaction, and it carries 280 A/mm -2 in a background field 14 T and generates an additional 1.7 T. A notable result is that,more » despite normal zones propagate slowly along the conductor, the hot spot temperature upon detection increases only from 40 K to 60 K when the resistive quench detection voltage threshold increases from 0.1 V to 1 V for all operating current density investigated, showing that quench detection using voltage taps is feasible for this coil. This is in a strong contrast to a coil we previously built to the same specifications but from wires insulated with the mullite braided sleeve insulation, for which the hot spot temperature upon detection increases from ~80 K to ~140 K while increasing from the detection voltage threshold from 0.1 V to 1 V, and thus for which quench detection using voltage taps presents significant risks, consistent with the common belief that the effectiveness of quench detection using voltage taps for superconducting magnets built using high temperature superconductors is seriously compromised by their slow normal zone propagation. This striking difference is ascribed to the fast transverse quench propagation enabled by thin insulation and improved thermal coupling between conductor turns. Finally, this work demonstrates that quench detection for high-temperature superconducting magnets highly depends on the design and construction of the coils such as insulation materials used and this dependence should be factored into the overall magnet design.« less

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

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.

Lithium ion insertion and extraction reactions with Hollandite-type manganese dioxide free from any stabilizing cations in its tunnel cavity

NASA Astrophysics Data System (ADS)

Kijima, Norihito; Takahashi, Yasuhiko; Akimoto, Junji; Awaka, Junji

2005-09-01

Lithium ion insertion and extraction reactions with a hollandite-type α-MnO 2 specimen free from any stabilizing cations in its tunnel cavity were investigated, and the crystal structure of a Li+-inserted α-MnO 2 specimen was analyzed by Rietveld refinement and whole-pattern fitting based on the maximum-entropy method (MEM). The pH titration curve of the α-MnO 2 specimen displayed a monobasic acid behavior toward Li+, and an ion-exchange capacity of 3.25 meq/g was achieved at pH>11. The Li/Mn molar ratio of the Li+-inserted α-MnO 2 specimen showed that about two Li+ ions can be chemically inserted into one unit cell of the hollandite-type structure. As the amount of Li content was increased, the lattice parameter a increased while c hardly changed. On the other hand, the mean oxidation number of Mn decreased slightly regardless of Li content whenever ions were exchanged. The Li+-inserted α-MnO 2 specimen reduced topotactically in one phase when it was used as an active cathode material in a liquid organic electrolyte (1:1 EC:DMC, 1 mol/dm 3 LiPF 6) lithium cell. An initial discharge with a capacity of approximately 230 mAh/g was achieved, and the reaction was reversible, whereas the capacity fell steadily upon cycling. About six Li+ ions could be electrochemically inserted into one unit cell of the hollandite-type structure. By contrast, the parent α-MnO 2 specimen showed a poor discharge property although no cationic residues or residual H 2O molecules remained in the tunnel space. Rietveld refinement from X-ray powder diffraction data for a Li+-inserted specimen of (Li 2O) 0.12MnO 2 showed it to have the hollandite-type structure (tetragonal; space group I4/m; a=9.993(11) and c=2.853(3) Å; Z=8; Rwp=6.12%, Rp=4.51%, RB=1.41%, and RF=0.79%; S=1.69). The electron-density distribution images in (Li 2O) 0.12MnO 2 showed that Li 2O molecules almost fill the tunnel space. These findings suggest that the presence of stabilizing atoms or molecules within the tunnel of a hollandite-type structure is necessary to facilitate the diffusion of Li+ ions during cycling.

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

Properties of large nearly perfect crystals at very low temperatures

NASA Technical Reports Server (NTRS)

Davis, W.; Krack, K. R.; Richard, J. P.; Weber, J.

1983-01-01

A liquid helium cryostat of a size and construction unavailable commercially, was built for use in measuring the Q of several materials at milli-Kelvin temperatures. The design and testing of the cryostat is described as well as the design of the experiment vacuum chamber and adaptor for the dilution refrigerator insert. Theory, design, and testing are also discussed for the magnetic coils built to levitate the materials so as to isolate them and increase the measured Q. A four point suspension with capacitor end plates as the transducer was used to obtain preliminary Q measurements of 6061 aluminum alloy and single crystal silicon. Results are tabulated.

Tube cutter tool and method of use for coupon removal

DOEpatents

Nachbar, H.D.; Etten, M.P. Jr.; Kurowski, P.A.

1997-05-06

A tube cutter tool is insertable into a tube for cutting a coupon from a damaged site on the exterior of the tube. Prior to using the tool, the damaged site is first located from the interior of the tube using a multi-coil pancake eddy current test probe. The damaged site is then marked. A fiber optic probe is used to monitor the subsequent cutting procedure which is performed using a hole saw mounted on the tube cutter tool. Prior to completion of the cutting procedure, a drill in the center of the hole saw is drilled into the coupon to hold it in place. 4 figs.

Cryogenic expansion joint for large superconducting magnet structures

DOEpatents

Brown, Robert L.

1978-01-01

An expansion joint is provided that accommodates dimensional changes occurring during the cooldown and warm-up of large cryogenic devices such as superconducting magnet coils. Flattened tubes containing a refrigerant such as gaseous nitrogen (N.sub.2) are inserted into expansion spaces in the structure. The gaseous N.sub.2 is circulated under pressure and aids in the cooldown process while providing its primary function of accommodating differential thermal contraction and expansion in the structure. After lower temperatures are reached and the greater part of the contraction has occured, the N.sub.2 liquefies then solidifies to provide a completely rigid structure at the cryogenic operating temperatures of the device.

Tube cutter tool and method of use for coupon removal

DOEpatents

Nachbar, Henry D.; Etten, Jr., Marvin P.; Kurowski, Paul A.

1997-01-01

A tube cutter tool is insertable into a tube for cutting a coupon from a damaged site on the exterior of the tube. Prior to using the tool, the damaged site is first located from the interior of the tube using a multi-coil pancake eddy current test probe. The damaged site is then marked. A fiber optic probe is used to monitor the subsequent cutting procedure which is performed using a hole saw mounted on the tube cutter tool. Prior to completion of the cutting procedure, a drill in the center of the hole saw is drilled into the coupon to hold it in place.

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.

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

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.

Lithium insertion in graphite from ternary ionic liquid-lithium salt electrolytes: II. Evaluation of specific capacity and cycling efficiency and stability at room temperature

NASA Astrophysics Data System (ADS)

Lux, Simon F.; Schmuck, Martin; Appetecchi, Giovanni B.; Passerini, Stefano; Winter, Martin; Balducci, Andrea

In this paper we report the results about the use of ternary room temperature ionic liquid-lithium salt mixtures as electrolytes for lithium-ion battery systems. Mixtures of N-methyl- N-propyl pyrrolidinium bis(fluorosulfonyl) imide, PYR 13FSI, and N-butyl- N-methylpyrrolidinium bis(trifluoromethansulfonyl) imide, PYR 14TFSI, with lithium hexafluorophosphate, LiPF 6 and lithium bis(trifluoromethansulfonyl) imide, LiTFSI, containing 5 wt.% of vinylene carbonate (VC) as additive, have been used in combination with a commercial graphite, KS6 TIMCAL. The performance of the graphite electrodes has been considered in term of specific capacity, cycling efficiency and cycling stability. The results clearly show the advantage of the use of ternary mixtures on the performance of the graphite electrode.

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.

[Intrauterine contraception].

PubMed

Tauber, P F

1984-09-01

Approximately 60 million women worldwide use IUDs. Despite worldwide distribution, the total number of IUD carriers has barely increased since 1970. Due to its risks and side effects there is a retrograding tendency both in West Germany and the US. To generate positive development, 3 basic trends have emerged: 1) Restrictive usage of the pharmacologically inactive, 1st generation IUDs such as the Lippes Loop or the Saf-T-Coil, 2) the increasing usage of small plastic IUDs with bioactive alloys to decrease failure rates such as the copper (2nd generation) or hormone-releasing IUDs, and 3) improvements made by changing its design to reduce side effects without loss of contraceptive effectiveness. Almost all IUDs increase monthly blood loss by 50-100%. The risk of illness for women with IUDs is 2-3 times higher than for a woman without or with other contraceptive methods. About 20% of all expulsions occur unnoticed. There are 2 kinds of perforations: primary (iatrogenic), at time of insertion, and secondary, some time after insertion. The IUD failure rate is about 1-3 pregnancies/100 woman years. In case of pregnancy, the IUD must be removed immediately. IUD insertion requires consent of the woman and can be made to women from 16 years on, presupposing moral maturity. IUD insertion after a miscarriage or abortion does not lead to risks or complications. Due to its corrosive quality, the copper IUD can only remain inside the uterus for a limited time. IUDs could become an excellent contraceptive method if it were possible to decrease bleeding, design easily-removeable IUDs, and prolong their potential for duration in the body.

10 years of protein crystallography at AR-NW12A beamline

NASA Astrophysics Data System (ADS)

Chavas, L. M. G.; Yamada, Y.; Hiraki, M.; Igarashi, N.; Matsugaki, N.; Wakatsuki, S.

2013-03-01

The exponential growth of protein crystallography can be observed in the continuously increasing demand for synchrotron beam time, both from academic and industrial users. Nowadays, the screening of a profusion of sample crystals for more and more projects is being implemented by taking advantage of fully automated procedures at every level of the experiments. The insertion device AR-NW12A beamline is one of the five macromolecular crystallography (MX) beamlines at the Photon Factory (PF). Currently the oldest MX beamline operational at the High Energy Accelerator Research Organization (KEK), the end-station was launched in 2001 as part of an upgrade of the PF Advanced Ring. Since its commissioning, AR-NW12A has been operating as a high-throughput beamline, slowly evolving to a multipurpose end-station for MX experiments. The development of the beamline took place about a decade ago, in parallel with a drastic development of protein crystallography and more general synchrotron technology. To keep the beamline up-to-date and competitive with other MX stations in Japan and worldwide, new features have been constantly added, with the goal of user friendliness of the various beamline optics and other instruments. Here we describe the evolution of AR-NW12A for its tenth anniversary. We also discuss the plans for upgrades for AR-NW12A, the future objectives in terms of the beamline developments, and especially the strong desire to open the beamline to a larger user community.

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

Treasure Na-ion anode from trash coke by adept electrolyte selection

NASA Astrophysics Data System (ADS)

Cabello, Marta; Chyrka, Taras; Klee, Rafael; Aragón, María J.; Bai, Xue; Lavela, Pedro; Vasylchenko, Gennadiy M.; Alcántara, Ricardo; Tirado, José L.; Ortiz, Gregorio F.

2017-04-01

Converting 'trash' waste residua to active functional materials 'treasure' with high added value is being regarded as a promising way to achieve the sustainable energy demands. Carbonaceous materials cannot insert sodium except when graphite co-intercalates solvents such as diglyme. Here, we show that petroleum coke and shale coke annealed at different temperatures can also insert sodium by reversible intercalation phenomena in a diglyme-based electrolyte. The structural and morphological studies will reveal significant differences justifying their distinct electrochemical behavior. Galvanostatic tests exhibit a flat plateau at about 0.7 V ascribable to the reversible reaction. At the end of the discharge, a Stage-I ternary intercalation compound is detected. Two diglyme molecules are co-intercalated per alkali ion, as evidenced by 1-D Patterson diagrams, FTIR and TGA analyses. The full sodium-ion cell made with P-2500/NaPF6(diglyme)/Na3V2(PO4)3 delivered an initial reversible capacity of 75 mA h g-1 at C rate and an average potential of 2.7 V. Thus, the full cell provides an energy density of 202 W h kg-1. This sodium-ion system can be considered a promising power source that encourages the potential use of low-cost energy storage systems.

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.

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

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.

Lung volume reduction for emphysema.

PubMed

Shah, Pallav L; Herth, Felix J; van Geffen, Wouter H; Deslee, Gaetan; Slebos, Dirk-Jan

2017-02-01

Advanced emphysema is a lung disease in which alveolar capillary units are destroyed and supporting tissue is lost. The combined effect of reduced gas exchange and changes in airway dynamics impairs expiratory airflow and leads to progressive air trapping. Pharmacological therapies have limited effects. Surgical resection of the most destroyed sections of the lung can improve pulmonary function and exercise capacity but its benefit is tempered by significant morbidity. This issue stimulated a search for novel approaches to lung volume reduction. Alternative minimally invasive approaches using bronchoscopic techniques including valves, coils, vapour thermal ablation, and sclerosant agents have been at the forefront of these developments. Insertion of endobronchial valves in selected patients could have benefits that are comparable with lung volume reduction surgery. Endobronchial coils might have a role in the treatment of patients with emphysema with severe hyperinflation and less parenchymal destruction. Use of vapour thermal energy or a sclerosant might allow focal treatment but the unpredictability of the inflammatory response limits their current use. In this Review, we aim to summarise clinical trial evidence on lung volume reduction and provide guidance on patient selection for available therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Two dimensional distribution measurement of electric current generated in a polymer electrolyte fuel cell using 49 NMR surface coils.

PubMed

Ogawa, Kuniyasu; Sasaki, Tatsuyoshi; Yoneda, Shigeki; Tsujinaka, Kumiko; Asai, Ritsuko

2018-05-17

In order to increase the current density generated in a PEFC (polymer electrolyte fuel cell), a method for measuring the spatial distribution of both the current and the water content of the MEA (membrane electrode assembly) is necessary. Based on the frequency shifts of NMR (nuclear magnetic resonance) signals acquired from the water contained in the MEA using 49 NMR coils in a 7 × 7 arrangement inserted in the PEFC, a method for measuring the two-dimensional spatial distribution of electric current generated in a unit cell with a power generation area of 140 mm × 160 mm was devised. We also developed an inverse analysis method to determine the two-dimensional electric current distribution that can be applied to actual PEFC connections. Two analytical techniques, namely coarse graining of segments and stepwise search, were used to shorten the calculation time required for inverse analysis of the electric current map. Using this method and techniques, spatial distributions of electric current and water content in the MEA were obtained when the PEFC generated electric power at 100 A. Copyright © 2018 Elsevier Inc. All rights reserved.

Stretchable, weavable coiled carbon nanotube/MnO2/polymer fiber solid-state supercapacitors.

PubMed

Choi, Changsoon; Kim, Shi Hyeong; Sim, Hyeon Jun; Lee, Jae Ah; Choi, A Young; Kim, Youn Tae; Lepró, Xavier; Spinks, Geoffrey M; Baughman, Ray H; Kim, Seon Jeong

2015-03-23

Fiber and yarn supercapacitors that are elastomerically deformable without performance loss are sought for such applications as power sources for wearable electronics, micro-devices, and implantable medical devices. Previously reported yarn and fiber supercapacitors are expensive to fabricate, difficult to upscale, or non-stretchable, which limits possible use. The elastomeric electrodes of the present solid-state supercapacitors are made by using giant inserted twist to coil a nylon sewing thread that is helically wrapped with a carbon nanotube sheet, and then electrochemically depositing pseudocapacitive MnO2 nanofibers. These solid-state supercapacitors decrease capacitance by less than 15% when reversibly stretched by 150% in the fiber direction, and largely retain capacitance while being cyclically stretched during charge and discharge. The maximum linear and areal capacitances (based on active materials) and areal energy storage and power densities (based on overall supercapacitor dimensions) are high (5.4 mF/cm, 40.9 mF/cm(2), 2.6 μWh/cm(2) and 66.9 μW/cm(2), respectively), despite the engineered superelasticity of the fiber supercapacitor. Retention of supercapacitor performance during large strain (50%) elastic deformation is demonstrated for supercapacitors incorporated into the wristband of a glove.

An Implantable RF Solenoid for Magnetic Resonance Microscopy and Microspectroscopy

PubMed Central

Cohen, Mark S.; Clark, W. Gilbert; Chu, Allen C.; Nunnally, Ray L.; Smith, Jolinda; Mills, Dixie; Judy, Jack W.

2014-01-01

Miniature solenoids routinely enhance small volume nuclear magnetic resonance imaging and spectroscopy; however, no such techniques exist for patients. We present an implantable microcoil for diverse clinical applications, with a microliter coil volume. The design is loosely based on implantable depth electrodes, in which a flexible tube serves as the substrate, and a metal stylet is inserted into the tube during implantation. The goal is to provide enhanced signal-to-noise ratio (SNR) of structures that are not easily accessed by surface coils. The first-generation prototype was designed for implantation up to 2 cm, and provided initial proof-of-concept for microscopy. Subsequently, we optimized the design to minimize the influence of lead inductances, and to thereby double the length of the implantable depth (4 cm). The second-generation design represents an estimated SNR improvement of over 30% as compared to the original design when extended to 4 cm. Impedance measurements indicate that the device is stable for up to 24 h in body temperature saline. We evaluated the SNR and MR-related heating of the device at 3T. The implantable microcoil can differentiate fat and water peaks, and resolve submillimeter features. PMID:22156945

A non-contact energy transferring system for an electric vehicle-charging system based on recycled products

NASA Astrophysics Data System (ADS)

Matsuda, Y.; Sakamoto, H.; Shibuya, H.; Murata, S.

2006-04-01

A non-contact automatic charging system for electric vehicle application is presented. The principle is the same as that of the transformer where the primary and the secondary circuits are separable but coupled with each other without using the hand coupler. In this paper, we present a possibility of removing the core of the secondary coil on the body for reducing the weight of the car. In our experiments, the primary core, which is placed on the earth floor, is made of Mn-Zn ferrite with square shape as 1 m×1 m×10 mm for a large cross-sectional area. The steel floor of the car assists to pass the magnetic flux. An efficiency rate over 90% with the test device of 2 kW is obtained without the conventional secondary core. The leakage inductance is well compensated by a resonance capacitor inserted in the secondary coil. In this experiment, the distance between the primary and the secondary coil is 100 mm and the switching frequency is 100 kHz. In addition, we developed a pavement method for the system. The method utilizes plates made from the waste of expanded polystyrene and rubber mats made from used tire. The plates are set up on the rubber mats and these mats are arranged over the non-contact charging system. The pavements can be replaced easily when the system is exchanged. Therefore, this pavement method is not only practical for the non-contact charging system but is also useful for recycling of resources and reduction of waste matters.

R1 dispersion contrast at high field with fast field-cycling MRI.

PubMed

Bödenler, Markus; Basini, Martina; Casula, Maria Francesca; Umut, Evrim; Gösweiner, Christian; Petrovic, Andreas; Kruk, Danuta; Scharfetter, Hermann

2018-05-01

Contrast agents with a strong R 1 dispersion have been shown to be effective in generating target-specific contrast in MRI. The utilization of this R 1 field dependence requires the adaptation of an MRI scanner for fast field-cycling (FFC). Here, we present the first implementation and validation of FFC-MRI at a clinical field strength of 3 T. A field-cycling range of ±100 mT around the nominal B 0 field was realized by inserting an additional insert coil into an otherwise conventional MRI system. System validation was successfully performed with selected iron oxide magnetic nanoparticles and comparison to FFC-NMR relaxometry measurements. Furthermore, we show proof-of-principle R 1 dispersion imaging and demonstrate the capability of generating R 1 dispersion contrast at high field with suppressed background signal. With the presented ready-to-use hardware setup it is possible to investigate MRI contrast agents with a strong R 1 dispersion at a field strength of 3 T. Copyright © 2018 Elsevier Inc. All rights reserved.

Methods and instruments for materials testing

NASA Technical Reports Server (NTRS)

Hansma, Paul (Inventor); Drake, Barney (Inventor); Rehn, Douglas (Inventor); Adams, Jonathan (Inventor); Lulejian, Jason (Inventor)

2011-01-01

Methods and instruments for characterizing a material, such as the properties of bone in a living human subject, using a test probe constructed for insertion into the material and a reference probe aligned with the test probe in a housing. The housing is hand held or placed so that the reference probe contacts the surface of the material under pressure applied either by hand or by the weight of the housing. The test probe is inserted into the material to indent the material while maintaining the reference probe substantially under the hand pressure or weight of the housing allowing evaluation of a property of the material related to indentation of the material by the probe. Force can be generated by a voice coil in a magnet structure to the end of which the test probe is connected and supported in the magnet structure by a flexure, opposing flexures, a linear translation stage, or a linear bearing. Optionally, a measurement unit containing the test probe and reference probe is connected to a base unit with a wireless connection, allowing in the field material testing.

Microstrip Butler matrix design and realization for 7 T MRI.

PubMed

Yazdanbakhsh, Pedram; Solbach, Klaus

2011-07-01

This article presents the design and realization of 8 × 8 and 16 × 16 Butler matrices for 7 T MRI systems. With the focus on low insertion loss and high amplitude/phase accuracy, the microstrip line integration technology (microwave-integrated circuit) was chosen for the realization. Laminate material of high permittivity (ε(r) = 11) and large thickness (h = 3.2 mm) is shown to allow the best trade-off of circuit board size versus insertion loss, saving circuit area by extensive folding of branch-line coupler topology and meandering phase shifter and connecting strip lines and reducing mutual coupling of neighboring strip lines by shield structures between strip lines. With this approach, 8 × 8 Butler matrices were produced in single boards of 310 mm × 530 mm, whereas the 16 × 16 Butler matrices combined two submatrices of 8 × 8 with two smaller boards. Insertion loss was found at 0.73 and 1.1 dB for an 8 × 8 matrix and 16 × 16 matrix, respectively. Measured amplitude and phase errors are shown to represent highly pure mode excitation with unwanted modes suppressed by 40 and 35 dB, respectively. Both types of matrices were implemented with a 7 T MRI system and 8- and 16-element coil arrays for RF mode shimming experiments and operated successfully with 8 kW of RF power. Copyright © 2011 Wiley-Liss, Inc.

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 ...

Rotation and neoclassical ripple transport in ITER

DOE PAGES

Paul, Elizabeth Joy; Landreman, Matt; Poli, Francesca M.; ...

2017-07-13

Neoclassical transport in the presence of non-axisymmetric magnetic fields causes a toroidal torque known as neoclassical toroidal viscosity (NTV). The toroidal symmetry of ITER will be broken by the finite number of toroidal field coils and by test blanket modules (TBMs). The addition of ferritic inserts (FIs) will decrease the magnitude of the toroidal field ripple. 3D magnetic equilibria in the presence of toroidal field ripple and ferromagnetic structures are calculated for an ITER steady-state scenario using the Variational Moments Equilibrium Code (VMEC). Furthermore, neoclassical transport quantities in the presence of these error fields are calculated using the Stellarator Fokker-Planckmore » Iterative Neoclassical Conservative Solver (SFINCS).« less

Water flow energy harvesters for autonomous flowmeters

NASA Astrophysics Data System (ADS)

Boisseau, Sebastien; Duret, Alexandre-Benoit; Perez, Matthias; Jallas, Emmanuel; Jallas, Eric

2016-11-01

This paper reports on a water flow energy harvester exploiting a horizontal axis turbine with distributed magnets of alternate polarities at the rotor periphery and air coils outside the pipe. The energy harvester operates down to 1.2L/min with an inlet section of 20mm of diameter and up to 25.2mW are provided at 20L/min in a 2.4V NiMH battery through a BQ25504 power management circuit. The pressure loss induced by the insertion of the energy harvester in the hydraulic circuit and by the extraction of energy has been limited to 0.05bars at 30L/min, corresponding to a minor loss coefficient of KEH=3.94.

Catheter Insertion Reference Trajectory Construction Method Using Photoelastic Stress Analysis for Quantification of Respect for Tissue During Endovascular Surgery Simulation

NASA Astrophysics Data System (ADS)

Tercero, Carlos; Ikeda, Seiichi; Fukuda, Toshio; Arai, Fumihito; Negoro, Makoto; Takahashi, Ikuo

2011-10-01

There is a need to develop quantitative evaluation for simulator based training in medicine. Photoelastic stress analysis can be used in human tissue modeling materials; this enables the development of simulators that measure respect for tissue. For applying this to endovascular surgery, first we present a model of saccular aneurism where stress variation during micro-coils deployment is measured, and then relying on a bi-planar vision system we measure a catheter trajectory and compare it to a reference trajectory considering respect for tissue. New photoelastic tissue modeling materials will expand the applications of this technology to other medical training domains.

Catheter tip force transducer for cardiovascular research

NASA Technical Reports Server (NTRS)

Feldstein, C.; Lewis, G. W.; Silver, R. H.; Culler, V. H. (Inventor)

1976-01-01

A force transducer for measuring dynamic force activity within the heart of a subject essentially consists of a U-shaped beam of low elastic compliance material. Two lines extend from the beams's legs and a long coil spring is attached to the beam. A strain gauge is coupled to one of the beam's legs to sense deflections thereof. The beam with the tines and most of the spring are surrounded by a flexible tube, defining a catheter, which is insertable into a subject's heart through an appropriate artery. The tines are extractable from the catheter for implantation into the myocardium by pushing on the end of the spring which extends beyond the external end of the catheter.

Rotation and neoclassical ripple transport in ITER

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

Paul, Elizabeth Joy; Landreman, Matt; Poli, Francesca M.

Neoclassical transport in the presence of non-axisymmetric magnetic fields causes a toroidal torque known as neoclassical toroidal viscosity (NTV). The toroidal symmetry of ITER will be broken by the finite number of toroidal field coils and by test blanket modules (TBMs). The addition of ferritic inserts (FIs) will decrease the magnitude of the toroidal field ripple. 3D magnetic equilibria in the presence of toroidal field ripple and ferromagnetic structures are calculated for an ITER steady-state scenario using the Variational Moments Equilibrium Code (VMEC). Furthermore, neoclassical transport quantities in the presence of these error fields are calculated using the Stellarator Fokker-Planckmore » Iterative Neoclassical Conservative Solver (SFINCS).« less

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

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

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

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.

A Plasmodium falciparum strain expressing GFP throughout the parasite's life-cycle.

PubMed

Talman, Arthur M; Blagborough, Andrew M; Sinden, Robert E

2010-02-10

The human malaria parasite Plasmodium falciparum is responsible for the majority of malaria-related deaths. Tools allowing the study of the basic biology of P. falciparum throughout the life cycle are critical to the development of new strategies to target the parasite within both human and mosquito hosts. We here present 3D7HT-GFP, a strain of P. falciparum constitutively expressing the Green Fluorescent Protein (GFP) throughout the life cycle, which has retained its capacity to complete sporogonic development. The GFP expressing cassette was inserted in the Pf47 locus. Using this transgenic strain, parasite tracking and population dynamics studies in mosquito stages and exo-erythrocytic schizogony is greatly facilitated. The development of 3D7HT-GFP will permit a deeper understanding of the biology of parasite-host vector interactions, and facilitate the development of high-throughput malaria transmission assays and thus aid development of new intervention strategies against both parasite and mosquito.

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.

Performance of a PET Insert for High-Resolution Small-Animal PET/MRI at 7 Tesla.

PubMed

Stortz, Greg; Thiessen, Jonathan D; Bishop, Daryl; Khan, Muhammad Salman; Kozlowski, Piotr; Retière, Fabrice; Schellenberg, Graham; Shams, Ehsan; Zhang, Xuezhu; Thompson, Christopher J; Goertzen, Andrew L; Sossi, Vesna

2018-03-01

We characterize a compact MR-compatible PET insert for simultaneous preclinical PET/MRI. Although specifically designed with the strict size constraint to fit inside the 114-mm inner diameter of the BGA-12S gradient coil used in the BioSpec 70/20 and 94/20 series of small-animal MRI systems, the insert can easily be installed in any appropriate MRI scanner or used as a stand-alone PET system. Methods: The insert consists of a ring of 16 detector-blocks each made from depth-of-interaction-capable dual-layer-offset arrays of cerium-doped lutetium-yttrium oxyorthosilicate crystals read out by silicon photomultiplier arrays. Scintillator crystal arrays are made from 22 × 10 and 21 × 9 crystals in the bottom and top layers, respectively, with respective layer thicknesses of 6 and 4 mm, arranged with a 1.27-mm pitch, resulting in a useable field of view 28 mm long and about 55 mm wide. Results: Spatial resolution ranged from 1.17 to 1.86 mm full width at half maximum in the radial direction from a radial offset of 0-15 mm. With a 300- to 800-keV energy window, peak sensitivity was 2.2% and noise-equivalent count rate from a mouse-sized phantom at 3.7 MBq was 11.1 kcps and peaked at 20.8 kcps at 14.5 MBq. Phantom imaging showed that features as small as 0.7 mm could be resolved. 18 F-FDG PET/MR images of mouse and rat brains showed no signs of intermodality interference and could excellently resolve substructures within the brain. Conclusion: Because of excellent spatial resolvability and lack of intermodality interference, this PET insert will serve as a useful tool for preclinical PET/MR. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

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

Poststroke upper-limb rehabilitation using 5 to 7 inserted microstimulators: implant procedure, safety, and efficacy for restoration of function.

PubMed

Davis, Ross; Sparrow, Owen; Cosendai, Gregoire; Burridge, Jane H; Wulff, Christian; Turk, Ruth; Schulman, Joseph

2008-10-01

To investigate the feasibility of implanting microstimulators to deliver programmed nerve stimulation for sequenced muscle activation to recover arm-hand functions. By using a minimally invasive procedure and local anesthesia, 5 to 7 microstimulators can be safely and comfortably implanted adjacent to targeted radial nerve branches in the arm and forearm of 7 subjects with poststroke paresis. The microstimulators' position should remain stable with no tissue infection and can be programmed to produce effective personalized functional muscle activity with no discomfort for a preliminary 12-week study. Clinical testing, before and after the study, is reported in the accompanying study. Microstimulator implantations in a sterile operating room. Seven adults, with poststroke hemiparesis of 12 months or more. Under local anesthesia, a stimulating probe was inserted to identify radial nerve branches. Microstimulators were inserted by using an introducer and were retrievable for 6 days by attached suture. Each device was powered via a radiofrequency link from 2 external cuff coils connected to a control unit. To achieve low threshold values at the target sites with minimal implant discomfort. Microstimulators and external equipment were monitored over 12 weeks of exercise. Seven subjects were implanted with 41 microstimulators, 5 to 7 per subject, taking 3.5 to 6 hours. Implantation pain levels were 20% more than anticipated. No infections or microstimulator failures occurred. Mean nerve thresholds ranged between 4.0 to 7.7 microcoulomb/cm(2)/phase over 90 days, indicating that cathodes were within 2 to 4 mm of target sites. In 1 subject, 2 additional microstimulators were inserted. Microstimulators were safely implanted with no infection or failure. The system was reliable and programmed effectively to perform exercises at home for functional restoration.

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.

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

Ethanol modulates cortical activity: direct evidence with combined TMS and EEG.

PubMed

Kähkönen, S; Kesäniemi, M; Nikouline, V V; Karhu, J; Ollikainen, M; Holi, M; Ilmoniemi, R J

2001-08-01

The motor cortex of 10 healthy subjects was stimulated by transcranial magnetic stimulation (TMS) before and after ethanol challenge (0.8 g/kg resulting in blood concentration of 0.77 +/- 0.14 ml/liter). The electrical brain activity resulting from the brief electromagnetic pulse was recorded with high-resolution electroencephalography (EEG) and located using inversion algorithms. Focal magnetic pulses to the left motor cortex were delivered with a figure-of-eight coil at the random interstimulus interval of 1.5-2.5 s. The stimulation intensity was adjusted to the motor threshold of abductor digiti minimi. Two conditions before and after ethanol ingestion (30 min) were applied: (1) real TMS, with the coil pressed against the scalp; and (2) control condition, with the coil separated from the scalp by a 2-cm-thick piece of plastic. A separate EMG control recording of one subject during TMS was made with two bipolar platinum needle electrodes inserted to the left temporal muscle. In each condition, 120 pulses were delivered. The EEG was recorded from 60 scalp electrodes. A peak in the EEG signals was observed at 43 ms after the TMS pulse in the real-TMS condition but not in the control condition or in the control scalp EMG. Potential maps before and after ethanol ingestion were significantly different from each other (P = 0.01), but no differences were found in the control condition. Ethanol changed the TMS-evoked potentials over right frontal and left parietal areas, the underlying effect appearing to be largest in the right prefrontal area. Our findings suggest that ethanol may have changed the functional connectivity between prefrontal and motor cortices. This new noninvasive method provides direct evidence about the modulation of cortical connectivity after ethanol challenge. Copyright 2001 Academic Press.

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.