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Sample records for resistive level shifters

  1. Source-Coupled, N-Channel, JFET-Based Digital Logic Gate Structure Using Resistive Level Shifters

    NASA Technical Reports Server (NTRS)

    Krasowski, Michael J.

    2011-01-01

    A circuit topography is used to create usable, digital logic gates using N (negatively doped) channel junction field effect transistors (JFETs), load resistors, level shifting resistors, and supply rails whose values are based on the DC parametric distributions of these JFETs. This method has direct application to the current state-of-the-art in high-temperature (300 to 500 C and higher) silicon carbide (SiC) device production, and defines an adaptation to the logic gate described in U.S. Patent 7,688,117 in that, by removing the level shifter from the output of the gate structure described in the patent (and applying it to the input of the same gate), a source-coupled gate topography is created. This structure allows for the construction AND/OR (sum of products) arrays that use far fewer transistors and resistors than the same array as constructed from the gates described in the aforementioned patent. This plays a central role when large multiplexer constructs are necessary; for example, as in the construction of memory. This innovation moves the resistive level shifter from the output of the basic gate structure to the front as if the input is now configured as what would be the output of the preceding gate, wherein the output is the two level shifting resistors. The output of this innovation can now be realized as the lone follower transistor with its source node as the gate output. Additionally, one may leave intact the resistive level shifter on the new gate topography. A source-coupled to direct-coupled logic translator will be the result.

  2. shifter

    SciTech Connect

    Jacobsen, Douglas

    2015-06-01

    Shifter enables application virtualization or containerization in large-scale HPC environments. This technology decreases the effort to port applications to or between HPC sites while increasing reproducibility and scientific productivity. Shifter works by converting application/container images to a common format, and then leverages basic Linux functionality to make that image available to batch jobs run in the HPC environment.

  3. 36. Perimeter acquisition radar building, phase shifter service platform; level ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    36. Perimeter acquisition radar building, phase shifter service platform; level three - Stanley R. Mickelsen Safeguard Complex, Perimeter Acquisition Radar Building, Limited Access Area, between Limited Access Patrol Road & Service Road A, Nekoma, Cavalier County, ND

  4. 37. Perimeter acquisition radar building, phase shifter service platform, level ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    37. Perimeter acquisition radar building, phase shifter service platform, level three; This shows the coaxial switches and transmitter output assembly (located only on this level) - Stanley R. Mickelsen Safeguard Complex, Perimeter Acquisition Radar Building, Limited Access Area, between Limited Access Patrol Road & Service Road A, Nekoma, Cavalier County, ND

  5. Low voltage to high voltage level shifter and related methods

    NASA Technical Reports Server (NTRS)

    Mentze, Erik J. (Inventor); Hess, Herbert L. (Inventor); Buck, Kevin M. (Inventor); Cox, David F. (Inventor)

    2006-01-01

    A shifter circuit comprises a high and low voltage buffer stages and an output buffer stage. The high voltage buffer stage comprises multiple transistors arranged in a transistor stack having a plurality of intermediate nodes connecting individual transistors along the stack. The transistor stack is connected between a voltage level being shifted to and an input voltage. An inverter of this stage comprises multiple inputs and an output. Inverter inputs are connected to a respective intermediate node of the transistor stack. The low voltage buffer stage has an input connected to the input voltage and an output, and is operably connected to the high voltage buffer stage. The low voltage buffer stage is connected between a voltage level being shifted away from and a lower voltage. The output buffer stage is driven by the outputs of the high voltage buffer stage inverter and the low voltage buffer stage.

  6. Reconfigurable, Bi-Directional Flexfet Level Shifter for Low-Power, Rad-Hard Integration

    NASA Technical Reports Server (NTRS)

    DeGregorio, Kelly; Wilson, Dale G.

    2009-01-01

    Two prototype Reconfigurable, Bi-directional Flexfet Level Shifters (ReBiLS) have been developed, where one version is a stand-alone component designed to interface between external low voltage and high voltage, and the other version is an embedded integrated circuit (IC) for interface between internal low-voltage logic and external high-voltage components. Targeting stand-alone and embedded circuits separately allows optimization for these distinct applications. Both ReBiLS designs use the commercially available 180-nm Flex fet Independently Double-Gated (IDG) SOI CMOS (silicon on insulator, complementary metal oxide semiconductor) technology. Embedded ReBiLS circuits were integrated with a Reed-Solomon (RS) encoder using CMOS Ultra-Low-Power Radiation Tolerant (CULPRiT) double-gated digital logic circuits. The scope of the project includes: creation of a new high-voltage process, development of ReBiLS circuit designs, and adjustment of the designs to maximize performance through simulation, layout, and manufacture of prototypes. The primary technical objectives were to develop a high-voltage, thick oxide option for the 180-nm Flexfet process, and to develop a stand-alone ReBiLS IC with two 8-channel I/O busses, 1.8 2.5 I/O on the low-voltage pins, 5.0-V-tolerant input and 3.3-V output I/O on the high-voltage pins, and 100-MHz minimum operation with 10-pF external loads. Another objective was to develop an embedded, rad-hard ReBiLS I/O cell with 0.5-V low-voltage operation for interface with core logic, 5.0-V-tolerant input and 3.3-V output I/O pins, and 100-MHz minimum operation with 10- pF external loads. A third objective was to develop a 0.5- V Reed-Solomon Encoder with embedded ReBilS I/O: Transfer the existing CULPRiT RS encoder from a 0.35-micron bulk-CMOS process to the ASI 180-nm Flexfet, rad-hard SOI Process. 0.5-V low-voltage core logic. 5.0-V-tolerant input and 3.3-V output I/O pins. 100-MHz minimum operation with 10- pF external loads. The stand

  7. Monolithically integrated enhancement/depletion-mode AlGaN/GaN HEMTs SRAM unit and voltage level shifter using fluorine plasma treatment

    NASA Astrophysics Data System (ADS)

    Yonghe, Chen; Xuefeng, Zheng; Jincheng, Zhang; Xiaohua, Ma; Yue, Hao

    2016-05-01

    A GaN-based E/D mode direct-couple logic 6 transistors SRAM unit and a voltage level shifter were designed and fabricated. E-mode and D-mode AlGaN/GaN HEMTs were integrated in one wafer using fluorine plasma treatment and using a moderate AlGaN barrier layer heterojunction structure. The 6 transistors SRAM unit consists of two symmetrical E/D mode inverters and two E-mode switch HEMTs. The output low and high voltage of the SRAM unit are 0.95 and 0.07 V at a voltage supply of 1 V. The voltage level shifter lowers the supply voltage using four Ni-AlGaN Schottky diodes in a series at a positive supply voltage of 6 V and a negative supply voltage of -6 V. By controlling the states of inverter modules of the level shifter in turn, the level shifter offers two channel voltage outputs of -0.5 and -5 V. The flip voltage of the level shifter is 0.76 V. Both the SRAM unit and voltage shifter operate correctly, demonstrating the promising potential for GaN-based E/D mode digital and analog integrated circuits. Several considerations are proposed to avoid the influence of threshold voltage degradation of D-mode and E-mode HEMT on the operation of the circuit. Project supported by the National Natural Science Foundation of China (No. 61334002), the Opening Project of Science and Technology on Reliability Physics and Application Technology of Electronic Component Laboratory (No. ZHD201206), and the Program for New Century Excellent Talents in University (No. NCET-12-0915).

  8. Compact-sized high-modulation-efficiency silicon Mach-Zehnder modulator based on a vertically dipped depletion junction phase shifter for chip-level integration.

    PubMed

    Kim, Gyungock; Park, Jeong Woo; Kim, In Gyoo; Kim, Sanghoon; Jang, Ki-Seok; Kim, Sun Ae; Oh, Jin Hyuk; Joo, Jiho; Kim, Sanggi

    2014-04-15

    We present small-sized depletion-type silicon Mach-Zehnder (MZ) modulator with a vertically dipped PN depletion junction (VDJ) phase shifter based on a CMOS compatible process. The fabricated device with a 100 μm long VDJ phase shifter shows a VπLπ of ∼0.6  V·cm with a 3 dB bandwidth of ∼50  GHz at -2  V bias. The measured extinction ratios are 6 and 5.3 dB for 40 and 50  Gb/s operation under 2.5  Vpp differential drive, respectively. On-chip insertion loss is 3 dB for the maximum optical transmission. This includes the phase-shifter loss of 1.88  dB/100  μm, resulting mostly from the extra optical propagation loss through the polysilicon-plug structure for electrical contact, which can be readily minimized by utilizing finer-scaled lithography nodes. The experimental result indicates that a compact depletion-type MZ modulator based on the VDJ scheme can be a potential candidate for future chip-level integration.

  9. Progress in ferrite phase shifters

    NASA Astrophysics Data System (ADS)

    Boyd, C. R., Jr.

    1983-10-01

    Advances in the technology of reciprocal ferrite phase shifters are outlined. Nonlatching rotary-field phase shifters have been produced with enhanced phase accuracy and modest control power. A significant quantity of dual-mode latching units has been built at 35 GHz, with good results. Both types of phase shifter can be adapted to perform other functions in addition to phase shifting. Examples of phase shifters that perform duplexing and polarization switching functions are given.

  10. High power phase shifter

    SciTech Connect

    Foster, B.; Gonin, I.; Khabiboulline, T.; Makarov, A.; Solyak, N.; Terechkine, I.; Wildman, D.; /Fermilab

    2005-05-01

    One of the approaches to power distribution system of a superconducting proton linac under discussion at FNAL requires development of a fast-action, megawatt-range phase shifter. Using a couple of this kind of devices with a waveguide hybrid junction can allow independent control of phase and amplitude of RF power at the input of each superconducting cavity, which will result in significant saving in number of klystrons and modulators required for the accelerator. A prototype of a waveguide version of the shifter that uses Yttrium-Iron Garnet (YIG) blocks was developed and tested. This report presents design concept of the device, and main results of simulation and proof-of-principle tests.

  11. 22. Perimeter acquisition radar building room #201, phase shifter service ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    22. Perimeter acquisition radar building room #201, phase shifter service platform (level two) - Stanley R. Mickelsen Safeguard Complex, Perimeter Acquisition Radar Building, Limited Access Area, between Limited Access Patrol Road & Service Road A, Nekoma, Cavalier County, ND

  12. Digitally controlled distributed phase shifter

    SciTech Connect

    Hietala, V.M.; Kravitz, S.H.; Vawter, G.A.

    1992-12-31

    A digitally controlled distributed phase shifter is comprised of N phase shifters. Digital control is achieved by using N binary length-weighted electrodes located on the top surface of a waveguide. A control terminal is attached to each electrode thereby allowing the application of a control signal. The control signal is either one of two discrete bias voltages. The application of the discrete bias voltages change the modal index of a portion of the waveguide that corresponds to a length of the electrode to which the bias voltage is applied, thereby causing the phase to change through the underlying portion of the waveguide. The digitally controlled distributed phase shift network has a total phase shift comprised of the sum of the individual phase shifters.

  13. Digitally controlled distributed phase shifter

    DOEpatents

    Hietala, Vincent M.; Kravitz, Stanley H.; Vawter, Gregory A.

    1993-01-01

    A digitally controlled distributed phase shifter is comprised of N phase shifters. Digital control is achieved by using N binary length-weighted electrodes located on the top surface of a waveguide. A control terminal is attached to each electrode thereby allowing the application of a control signal. The control signal is either one or two discrete bias voltages. The application of the discrete bias voltages changes the modal index of a portion of the waveguide that corresponds to a length of the electrode to which the bias voltage is applied, thereby causing the phase to change through the underlying portion of the waveguide. The digitally controlled distributed phase shift network has a total phase shift comprised of the sum of the individual phase shifters.

  14. Digitally controlled distributed phase shifter

    DOEpatents

    Hietala, V.M.; Kravitz, S.H.; Vawter, G.A.

    1993-08-17

    A digitally controlled distributed phase shifter is comprised of N phase shifters. Digital control is achieved by using N binary length-weighted electrodes located on the top surface of a waveguide. A control terminal is attached to each electrode thereby allowing the application of a control signal. The control signal is either one or two discrete bias voltages. The application of the discrete bias voltages changes the modal index of a portion of the waveguide that corresponds to a length of the electrode to which the bias voltage is applied, thereby causing the phase to change through the underlying portion of the waveguide. The digitally controlled distributed phase shift network has a total phase shift comprised of the sum of the individual phase shifters.

  15. A Ka-band GaAs monolithic phase shifter

    NASA Technical Reports Server (NTRS)

    Sokolov, V.; Geddes, J. J.; Contolatis, A.; Bauhahn, P. E.; Chao, C.

    1983-01-01

    The design and performance of a GaAs monolithic 180-degree one-bit switched line phase shifter test circuit for Ka-band operation is presented. A self-aligned gate (SAG) fabrication technique is also described that reduces resistive parasitics in the switching FET's. Over the 27.5-30 GHz band, typical measured differential insertion phase is within 10-20 deg of the ideal time delay characteristic. Over the same band, the insertion loss for the SAG phase shifter is about 2.5-3 dB per bit. The SAG fabrication technique holds promise in reducing phase shifter insertion loss to about 1.5 dB/bit for 30-GHz operation.

  16. A Ka-band reflection-type analog electrically controlled phase shifter

    NASA Astrophysics Data System (ADS)

    Li, Wenchao; Chen, Yanhui; Shen, Hui; Zhang, Bin

    2017-03-01

    In order to modulate the phase of RF signal continuously, a new miniaturized Ka-band analog electrically controlled phase shifter is presented. The phase shifter based on 90°directional coupler and parallel variable capacitance diodes(VCD) achieves matching circuit and shift phase, the circuit can gain wide range phase shift by changing the bias voltage of variable capacitance diodes (VCD), and the insertion loss fluctuations of the phase shifter has a significant improvement by parallel compensation resistance. Simulation and experimental results show that the phase shifter in 29˜31 GHz range obtains 180° phase shift, the insertion loss is better than 6.5 dB, and the insertion loss fluctuations are within 1 dB.

  17. Light-driven phase shifter

    DOEpatents

    Early, James W.

    1990-01-01

    A light-driven phase shifter is provided for modulating a transmission light beam. A gaseous medium such as argon is provided with electron energy states excited to populate a metastable state. A tunable dye laser is selected with a wavelength effective to deplete the metastable electron state and may be intensity modulated. The dye laser is directed through the gaseous medium to define a first optical path having an index of refraction determined by the gaseous medium having a depleted metastable electron state. A transmission laser beam is also directed through the gaseous medium to define a second optical path at least partially coincident with the first optical path. The intensity of the dye laser beam may then be varied to phase modulate the transmission laser beam.

  18. Array Phase Shifters: Theory and Technology

    NASA Technical Reports Server (NTRS)

    Romanofsky, Robert R.

    2007-01-01

    While there are a myriad of applications for microwave phase shifters in instrumentation and metrology, power combining, amplifier linearization, and so on, the most prevalent use is in scanning phased-array antennas. And while this market continues to be dominated by military radar and tracking platforms, many commercial applications have emerged in the past decade or so. These new and potential applications span low-Earth-orbit (LEO) communications satellite constellations and collision warning radar, an aspect of the Intelligent Vehicle Highway System or Automated Highway System. In any case, the phase shifters represent a considerable portion of the overall antenna cost, with some estimates approaching 40 percent for receive arrays. Ferrite phase shifters continue to be the workhorse in military-phased arrays, and while there have been advances in thin film ferrite devices, the review of this device technology in the previous edition of this book is still highly relevant. This chapter will focus on three types of phase shifters that have matured in the past decade: GaAs MESFET monolithic microwave integrated circuit (MMIC), micro-electromechanical systems (MEMS), and thin film ferroelectric-based devices. A brief review of some novel devices including thin film ferrite phase shifters and superconducting switches for phase shifter applications will be provided. Finally, the effects of modulo 2 phase shift limitations, phase errors, and transient response on bit error rate degradation will be considered.

  19. Tunable ceramic phase shifters and their applications

    NASA Astrophysics Data System (ADS)

    Selmi, Fathi; Hughes, Raymond; Varadan, Vijay K.; Varadan, Vasundara V.

    1993-07-01

    There is considerable interest in the development of microwave ceramic phase shifters because of limitations of currently available ferrite and PIN diode phase shifters regarding cost and reliability and complexity. Ceramic phase shifters may provide a cost breakthrough for the phased array antenna designer while maintaining low insertion losses and low drive power and high power handling capacity. This paper describes ceramic phase shifters which utilize a ferroelectric material [(Ba-Sr)TiO3 series] for obtaining phase shifts from changes in dc biasing fields. Also, the dielectric properties are measured as a function of dc biasing fields, frequency and temperature for a few compositions of barium-strontium titanate material. For the frequency range of 400 MHz to 5 GHz, differential phase shift is obtained by a dc voltage-controlled lumped barium-strontium titanate capacitor in a coaxial line or stripline medium. For 5 to 18 GHz frequency range, a barium-strontium titanate material which partially or completely fills the rectangular waveguide is required for the construction of a ceramic phase shifter.

  20. Ka-band full-360° analog phase shifter with low insertion loss

    NASA Astrophysics Data System (ADS)

    Mengyi, Cao; Yang, Lu; Jiaxing, Wei; Jiaxin, Zheng; Xiaohua, Ma; Yue, Hao

    2014-10-01

    A new reflection-type wideband 360° monolithic-microwave integrated-circuit (MMIC) analog phase shifter at the Ka-band is proposed. The phase shifter is designed based on the principle of vector synthesis. Three Lange couplers are employed in the phase shifter, which is fabricated by the standard 0.25-μm GaAs process. We use four 4 × 40 μm GaAs HEMTs as the reflection loads. A microstrip line in parallel with the device is used as an inductance to counteract the parasitic capacitance of the device so that the reflection load performs like a pure resistance and the insertion loss can be decreased. In this phase shifter, a folded Lange coupler is utilized to reduce the size of the chip. The size of the proposed MMIC phase shifter is only 2.0 × 1.2 mm2. The measurement results show that the insertion loss is 5.0 ± 0.8 dB and a 360° continuously tunable range across 27-32 GHz is obtained with miniscule DC power consumption.

  1. A wide range, high yield and good performance pHEMT switch for MMIC phase shifter

    NASA Astrophysics Data System (ADS)

    Menbari, Babak; Dousti, Massoud; Hajghassem, Hassan

    2014-11-01

    A low-cost method with high yield and good performance is presented by pHEMTs (pseudomorphic high electron mobility transistors) to be used in phase shifter switches. In this method, the capacitor in "off" mode (Coff) of transistor is reduced, without variation of the transistor structure. The transistor structure in switch mode can be optimised. This method increases the transistor isolation in turn "off" mode, while there is no change in resistance of the transistor in "on" mode (Ron). Transistor dimension is determined in turn "off" mode (Vg = -4.5 V) and standard form of 4 × 75 μm. So, in this method, insertion loss will be reduced without a perceptible change in transistor dimension. Thus, design and fabrication capability of some circuits such as phase shifters, antenna switches, SPDT (single port double throw) - without any change in technology - are increasing. In this paper, post layout and measurement result for a sample block of phase shifter are shown.

  2. A Model for Ferroelectric Phase Shifters

    NASA Technical Reports Server (NTRS)

    Romanofsky, Robert R.; Qureshi, A. Haq

    2000-01-01

    Novel microwave phase shifters consisting of coupled microstrip lines on thin ferroelectric films have been demonstrated recently. A theoretical model useful for predicting the propagation characteristics (insertion phase shift, dielectric loss, impedance, and bandwidth) is presented here. The model is based on a variational solution for line capacitance and coupled strip transmission line theory.

  3. Controllable Liquid Artificial Dielectric S-Band Phase Shifters

    DTIC Science & Technology

    1975-02-01

    IcNamara now on leave of absence to the University for conducting all work on phase shifter design, low pout,- testins anw his contribution to the paper...toward inalog, recipiroeal devie, tMal nre simple In construction. can ht produhcN aM low c0ost in smill quan- titles., can handle hIN power levels, and...Effects ..................... 50 7 LOW O%* WER TESTING .............................. 53 7.1 Insertion Loss. Electrode Deslp .............. ... 53 7.2

  4. Integrated optomechanical single-photon frequency shifter

    NASA Astrophysics Data System (ADS)

    Fan, Linran; Zou, Chang-Ling; Poot, Menno; Cheng, Risheng; Guo, Xiang; Han, Xu; Tang, Hong X.

    2016-12-01

    The ability to manipulate single photons is of critical importance for fundamental quantum optics studies and practical implementations of quantum communications. While extraordinary progresses have been made in controlling spatial, temporal, spin and orbit angular momentum degrees of freedom, frequency-domain control of single photons so far relies on nonlinear optical effects, which have faced obstacles such as noise photons, narrow bandwidth and demanding optical filtering. Here, we demonstrate the first integrated optomechanical single-photon frequency shifter with near-unity efficiency. A frequency shift up to 150 GHz at telecom wavelength is realized without measurable added noise and the preservation of quantum coherence is verified through quantum interference between twin photons of different colours. This single-photon frequency shifter will be invaluable for increasing the channel capacity of quantum communications and compensating frequency mismatch between quantum systems, paving the road towards a hybrid quantum network.

  5. Power transmission line operating modes calculation with controllable phase shifters

    NASA Astrophysics Data System (ADS)

    Astashev, M. G.; Novikov, M. A.; Panfilov, D. I.; Rashitov, P. A.; Remizevich, T. V.; Fedorova, M. I.

    2016-12-01

    The article contains the analysis of the influence of the phase shifter (PS) on the energy processes in the power transmission line in terms of the two-unit model of the electric network. The approach to synthesis of the models regulated by the phase shifter providing for both calculation of the steady operation modes of the electric networks with the phase shifters and research of the electromagnetic processes and designing of the device itself is offered.

  6. Ceramic phase shifters for electronically steerable antenna systems

    NASA Astrophysics Data System (ADS)

    Selmi, F.; Ghodgaonkar, D. K.; Hughes, R.; Varadan, V. V.; Varadan, V. K.

    1991-10-01

    There is considerable interest in the development of microwave ceramic phase shifters because of limitations of currently available ferrite and PIN diode phase shifters regarding cost and reliability and complexity. Ceramic phase shifters may provide a cost breakthrough for the phase array antenna designer while maintaining low insertion loss and low drive power and high power handling capacity. This paper describes a ceramic phase shifter which utilizes a ferroelectric material for obtaining phase shifts from changes in dc biasing fields. Also, the dielectric properties were measured as a function of dc biasing fields, frequency, and temperature for a few compositions of barium-strontium titanate material.

  7. Data-Driven Contextual Valence Shifter Quantification for Multi-Theme Sentiment Analysis.

    PubMed

    Yu, Hongkun; Shang, Jingbo; Hsu, Meichun; Castellanos, Malú; Han, Jiawei

    2016-10-01

    Users often write reviews on different themes involving linguistic structures with complex sentiments. The sentiment polarity of a word can be different across themes. Moreover, contextual valence shifters may change sentiment polarity depending on the contexts that they appear in. Both challenges cannot be modeled effectively and explicitly in traditional sentiment analysis. Studying both phenomena requires multi-theme sentiment analysis at the word level, which is very interesting but significantly more challenging than overall polarity classification. To simultaneously resolve the multi-theme and sentiment shifting problems, we propose a data-driven framework to enable both capabilities: (1) polarity predictions of the same word in reviews of different themes, and (2) discovery and quantification of contextual valence shifters. The framework formulates multi-theme sentiment by factorizing the review sentiments with theme/word embeddings and then derives the shifter effect learning problem as a logistic regression. The improvement of sentiment polarity classification accuracy demonstrates not only the importance of multi-theme and sentiment shifting, but also effectiveness of our framework. Human evaluations and case studies further show the success of multi-theme word sentiment predictions and automatic effect quantification of contextual valence shifters.

  8. Data-Driven Contextual Valence Shifter Quantification for Multi-Theme Sentiment Analysis

    PubMed Central

    Yu, Hongkun; Shang, Jingbo; Hsu, Meichun; Castellanos, Malú; Han, Jiawei

    2017-01-01

    Users often write reviews on different themes involving linguistic structures with complex sentiments. The sentiment polarity of a word can be different across themes. Moreover, contextual valence shifters may change sentiment polarity depending on the contexts that they appear in. Both challenges cannot be modeled effectively and explicitly in traditional sentiment analysis. Studying both phenomena requires multi-theme sentiment analysis at the word level, which is very interesting but significantly more challenging than overall polarity classification. To simultaneously resolve the multi-theme and sentiment shifting problems, we propose a data-driven framework to enable both capabilities: (1) polarity predictions of the same word in reviews of different themes, and (2) discovery and quantification of contextual valence shifters. The framework formulates multi-theme sentiment by factorizing the review sentiments with theme/word embeddings and then derives the shifter effect learning problem as a logistic regression. The improvement of sentiment polarity classification accuracy demonstrates not only the importance of multi-theme and sentiment shifting, but also effectiveness of our framework. Human evaluations and case studies further show the success of multi-theme word sentiment predictions and automatic effect quantification of contextual valence shifters. PMID:28232874

  9. Dye mixtures for ultrafast wavelength shifters

    SciTech Connect

    Gangopadhyay, S.; Liu, L.; Palsule, C.; Borst, W.; Wigmans, R.; Barashkov, N.

    1994-12-31

    Particle detectors based on scintillation processes have been used since the discovery of radium about 100 years ago. The fast signals that can be obtained with these detectors, although often considered a nice asset, were rarely essential for the success of experiments. However, the new generation of high energy particle accelerators require particle detectors with fast response time. The authors have produced fast wavelength shifters using mixtures of various Coumarin dyes with DCM in epoxy-polymers (DGEBA+HHPA) and measured the properties of these wavelength shifters. The particular mixtures were chosen because there is a substantial overlap between the emission spectrum of Coumarin and the absorption spectrum of DCM. The continuous wave and time-resolved fluorescence spectra have been studied as a function of component concentration to optimize the decay times, emission peaks and quantum yields. The mean decay times of these mixtures are in the range of 2.5--4.5 ns. The mean decay time increases with an increase in Coumarin concentration at a fixed DCM concentration or with a decrease in DCM concentration at a fixed Coumarin concentration. This indicates that the energy transfer is radiative at lower relative DCM concentrations and becomes non-radiative at higher DCM concentrations.

  10. A magnetoelectric composite based microwave phase shifter

    NASA Astrophysics Data System (ADS)

    Bichurin, M. I.; Petrov, V. M.; Srinivasan, G.

    2008-03-01

    Magnetoelectric (ME) properties of ferrite-ferroelectric composites arise from their response to elastic and electromagnetic force fields. The unique combination of magnetic, electrical, and ME interactions opens up the possibility of electric field tunable ferromagnetic resonance (FMR) based devices [1]. Here we discuss an ME phase shifter operating in the FMR region at 9.3 GHz. A slot line on a yttrium iron garnet film bonded to lead zirconate titanate (PZT) provides a basis for the phase shifter. The circularly polarized microwave magnetic field of the slot line interacts with the ferrite and causes variation of phase velocity with the controlling magnetic and electric fields. Electrical tuning is realized with the application of a control voltage due to PZT. The estimated phase shift per unit length and unit voltage is to 20 deg/cm kV for a PZT thickness of 0.5 mm. 1 S. Shastry and G. Srinivasan, M.I. Bichurin, V.M. Petrov, A.S. Tatarenko. Phys. Rev. B, 70 064416 (2004). - supported by grants from the Office of Naval Research and the Russian Foundation for Basic Research.

  11. Fiber optic microbend phase shifter and modulator

    NASA Astrophysics Data System (ADS)

    Taylor, H. F.

    1985-09-01

    The present invention relates generally to a fiber optic phase shifter and intensity modulator and more particularly to fiber optic phase shifters and modulators that utilize a microbend transducer. The ability to shift the phase of light propagating in a single mode fiber is quite useful in fiber optic sensors and may also be used in fiber-optic communications. A conventional way to shift the phase of light propagating in a single mode fiber is by stretching the fiber. This is done by wrapping and gluing the fiber around a cylinder of piezoelectric material. When a voltage is applied to the material, the cylinder expands thereby stretching the fiber. Long lengths on the order of 10 meters of fiber and large voltages are needed to drive the piezoelectric cylinder. The ability to modulate the intensity of light propagating in a optic fiber is also useful in fiber optic communication and sensing systems. Such modulation can be performed by a device external to the fiber such as an electrooptic modulator formed in a lithium niobate crystal.

  12. Nonlinear multiferroic phase shifters for microwave frequencies

    SciTech Connect

    Ustinov, Alexey B.; Kalinikos, Boris A.; Srinivasan, G.

    2014-02-03

    A nonlinear microwave phase shifter based on a planar multiferroic composite has been studied. The multiferroic structure is fabricated in the form of a bilayer consisting of yttrium iron garnet and barium strontium titanate. The principle of operation of the device is based on the linear and nonlinear control of the phase shift of the hybrid spin-electromagnetic waves propagating in the bilayer. The linear control is realized with magnetic and electric fields. The nonlinear control is provided by the input power of microwave signal. The device showed a nonlinear phase shift up to 250°, electric field induced phase shift up to 330°, and magnetic field induced phase shift of more than 180°.

  13. High-power femtosecond Raman frequency shifter.

    PubMed

    Vicario, Carlo; Shalaby, Mostafa; Konyashchenko, Aleksandr; Losev, Leonid; Hauri, Christoph P

    2016-10-15

    We report on the generation of broadband, high-energy femtosecond pulses centered at 1.28 μm by stimulated Raman scattering in a pressurized hydrogen cell. Stimulated Raman scattering is performed by two chirped and delayed pulses originating from a multi-mJ Ti:sapphire amplifier. The Stokes pulse carries record-high energy of 4.4 mJ and is recompressed down to 66 fs by a reflective grating pair. We characterized the short-wavelength mid-infrared source in view of energy stability, beam profile, and conversion efficiency at repetition rates of 100 and 10 Hz. The demonstrated high-energy frequency shifter will benefit intense THz sources based on highly nonlinear organic crystals.

  14. A Yttrium Iron Garnet-Lead Zirconate Titanate Phase Shifter

    NASA Astrophysics Data System (ADS)

    Srinivasan, G.; Tatarenko, A. S.; Bichurin, M. I.

    2006-03-01

    Tunable microwave phase shifters are of interest for miniature oscillators and phased array antenna systems. Traditional ferrite phase shifters use magnetic tuning systems that are slow, demand high power, and are not miniature in size. Here we discuss the design, fabrication and characterization of a novel electric field tunable phase shifter based on a yttrium iron garnet (YIG) -- lead zirconate titanate (PZT) bilayer. The electrical control of the phase shift is realized through magnetoelectric (ME) interaction. The phase shifter consisted of a microstrip transmission line with stubs of λ/8 and 3λ/8 lengths for generating circularly polarized microwave magnetic field in the YIG-PZT resonator. The ME resonator was made from 124 micron thick (100) YIG film on GGG and 0.5 mm thickness PZT with electrodes. The operating frequency of the phase shifter was set by applying appropriate bias magnetic field. The phase shift vs. electric field E characteristics was linear or quadratic in E, depending on the operating frequency. The maximum phase shift was 180 deg. and showed an insertion loss of 1.5-2.0 dB at 5 GHz and 3-4 dB at the frequency 10 GHz. The ME phase shifter is capable of rapid tuning, miniature in size and dissipates practically zero power. -- The work was supported by grants from ONR, ARO and NSF.

  15. Confirmation of resistance to herbicides and evaluation of resistance levels

    Technology Transfer Automated Retrieval System (TEKTRAN)

    As cases of resistance to herbicides escalate worldwide, there is increasing demand from growers to test for weed resistance and how to manage it. Scientists have developed resistance testing protocols for numerous herbicides and weed species. Growers need immediate answers and scientists are faced ...

  16. Analysis and Optimization of Thin Film Ferroelectric Phase Shifters

    NASA Technical Reports Server (NTRS)

    Romanofsky, Robert R.; VanKeuls, Fred W.; Warner, Joseph D.; Mueller, Carl H.; Alterovitz, Samuel A.; Miranda, Felix A.; Qureshi, A. Haq; Romanofsky, Robert R. (Technical Monitor)

    2000-01-01

    Microwave phase shifters have been fabricated from (YBa2Cu3O(7-delta) or Au)/SrTiO3 and Au/Ba(x)Sr(1-x)TiO3 films on LaAlO3 and MgO substrates. These coupled microstrip devices rival the performance of their semiconductor counter-parts parts at Ku- and K-band frequencies. Typical insertion loss for room temperature ferroelectric phase shifters at K-band is approximately equal 5 dB. An experimental and theoretical investigation of these novel devices explains the role of the ferroelectric film in overall device performance. A roadmap to the development of a 3 dB insertion loss phase shifter that would enable a new type of phased array antenna is discussed.

  17. Ka-band reliable and compact 3-bit true-time-delay phase shifter using MEMS single-pole-eight-throw switching networks

    NASA Astrophysics Data System (ADS)

    Koul, Shiban K.; Dey, Sukomal; Poddar, Ajay K.; Rohde, Ulrich L.

    2016-10-01

    This paper presents a radio frequency micro-electromechanical system (RF MEMS) based 3-bit phase shifter using MEMS single-pole-eight-throw (SP8T) switches. Devices are fabricated on 635 µm alumina substrate utilizing on the coplanar waveguide (CPW) transmission line. Single switch dimensions are 0.14  ×  0.23 mm2 which is much smaller than Si-on-insulator switches. The symmetric and compact SP8T switch is the primary building block of the 3-bit phase shifter. The SP8T switch results in isolation levels of 31-15 dB, return loss of 33-18 dB and insertion loss of 0.6-1.9 dB, respectively, at 26-40 GHz. Later, two SP8T switches are connected back to back to develop the 3-bit phase shifter using different delay lines at 35 GHz. Finally, the phase shifter provides average return loss of better than 14 dB and average insertion loss of 4.4 dB over the 34.75-35.25 GHz. Measured average phase error is less than 0.98° at 35 GHz. The total area of the fabricated 3-bit phase shifter is 5.95 mm2. SP8T switches are capable of handling 0.1-1 W of power up to 100 million cycles which is sufficient power handling capability for wireless communication systems. Reliability of the phase shifter is extensively characterized with different incident RF powers at room temperature (25°C) and discussed in detail. To the best of the authors’ knowledge, this is the first reported MEMS 3-bit phase shifter in the literature that has used a minimum number of switching elements per phase state.

  18. Design and development of a CPW-based 5-bit switched-line phase shifter using inline metal contact MEMS series switches for 17.25 GHz transmit/receive module application

    NASA Astrophysics Data System (ADS)

    Dey, Sukomal; Koul, Shiban K.

    2014-01-01

    A radio frequency micro-electro-mechanical system (RF-MEMS) phase shifter based on switchable delay line concept with maximum desirable phase shift and good reliability is presented in this paper. The phase shifter is based on the switchable reference and delay line configurations with inline metal contact series switches that employs MEMS systems based on electrostatic actuation and implemented using coplanar waveguide (CPW) configuration. Electromechanical behaviour of the MEMS switch has been extensively investigated using commercially available simulation tools and validated using system level simulation. A detailed design and performance analysis of the phase shifter has been carried out as a function of various structural parameters with reference to the gold-based surface micromachining process on alumina substrate. The mechanical, electrical, transient, intermodulation distortion (IMD) and loss performance of an MEMS switch have been experimentally investigated. The individual primary phase-bits (11.25°/22.5°/45°/90°/180°) that are fundamental building blocks of a complete 5-bit phase shifter have been designed, fabricated and experimentally characterized. Furthermore, two different 5-bit switched-line phase shifters, that lead to 25% size reduction and result in marked improvement in the reliability of the complete 5-bit phase shifter with 30 V actuation voltage, have been developed. The performance comparison between two different CPW-based switched-line phase shifters have been extensively investigated and validated. The complete 5-bit phase shifter demonstrates an average insertion loss of 5.4 dB with a return loss of better than 14 dB at 17.25 GHz. The maximum phase error of 1.3° has been obtained at 17.25 GHz from these 5-bit phase shifters.

  19. Does high serum uric acid level cause aspirin resistance?

    PubMed

    Yildiz, Bekir S; Ozkan, Emel; Esin, Fatma; Alihanoglu, Yusuf I; Ozkan, Hayrettin; Bilgin, Murat; Kilic, Ismail D; Ergin, Ahmet; Kaftan, Havane A; Evrengul, Harun

    2016-06-01

    In patients with coronary artery disease (CAD), though aspirin inhibits platelet activation and reduces atherothrombotic complications, it does not always sufficiently inhibit platelet function, thereby causing a clinical situation known as aspirin resistance. As hyperuricemia activates platelet turnover, aspirin resistance may be specifically induced by increased serum uric acid (SUA) levels. In this study, we thus investigated the association between SUA level and aspirin resistance in patients with CAD. We analyzed 245 consecutive patients with stable angina pectoris (SAP) who in coronary angiography showed more than 50% occlusion in a major coronary artery. According to aspirin resistance, two groups were formed: the aspirin resistance group (Group 1) and the aspirin-sensitive group (Group 2). Compared with those of Group 2, patients with aspirin resistance exhibited significantly higher white blood cell counts, neutrophil counts, neutrophil-to-lymphocyte ratios, SUA levels, high-sensitivity C-reactive protein levels, and fasting blood glucose levels. After multivariate analysis, a high level of SUA emerged as an independent predictor of aspirin resistance. The receiver-operating characteristic analysis provided a cutoff value of 6.45 mg/dl for SUA to predict aspirin resistance with 79% sensitivity and 65% specificity. Hyperuricemia may cause aspirin resistance in patients with CAD and high SUA levels may indicate aspirin-resistant patients. Such levels should thus recommend avoiding heart attack and stroke by adjusting aspirin dosage.

  20. Phase shifters. Citations from the NTIS data base

    NASA Astrophysics Data System (ADS)

    Reed, W. E.

    1980-05-01

    The bibliography cites Federally-funded research on the design, performance, and utilization of phase shifters and phase shift circuits. The types include ferrite, semiconductor, digital, and voltage controlled. Applications cover phased arrays, microwave equipment, surface acoustic wave devices, strip transmission lines, phases shift keyers, signal processors, and control equipment. This updated bibliography contains 20 abstracts.

  1. Analysis and comparison of different phase shifters for Stirling pulse tube cryocooler

    NASA Astrophysics Data System (ADS)

    Lei, Tian; Pfotenhauer, John M.; Zhou, Wenjie

    2016-12-01

    Investigations of phase shifters and power recovery mechanisms are of sustainable interest for developing Stirling pulse tube cryocoolers (SPTC) with higher power density, more compact design and higher efficiency. This paper investigates the phase shifting capacity and the applications of four different phase shifters, including conventional inertance tube, gas-liquid and spring-oscillator phase shifters, as well as a power recovery displacer. Distributed models based on the electro-acoustic analogy are developed to estimate the phase shifting capacity and the acoustic power dissipation of the three phase shifters without power recovery. The results show that both gas-liquid and spring-oscillator phase shifters have the distinctive capacity of phase shifting with a significant reduction in the inertial component length. Furthermore, full distributed models of SPTCs connected with different phase shifters are developed. The cooling performance of SPTCs using all four phase shifters are presented and typical phase relations are analyzed. The comparison reveals that the power recovery displacer with a more complicated configuration provides the highest efficiency. The gas-liquid and spring-oscillator phase shifters show equivalent efficiency compared with the inertance tube phase shifter. Approximately 10-20% of the acoustic power is dissipated by the phase shifters without power recovery, while 15-20% of the acoustic power can be recovered by the power recovery displacer, leading to a maximum coefficient of performance (COP) above 0.14 at 80 K. A merit analysis is also done by presenting the pros and cons of different phase shifters.

  2. Interference Confocal Microscope Integrated with Spatial Phase Shifter

    PubMed Central

    Wang, Weibo; Gu, Kang; You, Xiaoyu; Tan, Jiubin; Liu, Jian

    2016-01-01

    We present an interference confocal microscope (ICM) with a new single-body four-step simultaneous phase-shifter device designed to obtain high immunity to vibration. The proposed ICM combines the respective advantages of simultaneous phase shifting interferometry and bipolar differential confocal microscopy to obtain high axis resolution, large dynamic range, and reduce the sensitivity to vibration and reflectance disturbance seamlessly. A compact single body spatial phase shifter is added to capture four phase-shifted interference signals simultaneously without time delay and construct a stable and space-saving simplified interference confocal microscope system. The test result can be obtained by combining the interference phase response and the bipolar property of differential confocal microscopy without phase unwrapping. Experiments prove that the proposed microscope is capable of providing stable measurements with 1 nm of axial depth resolution for either low- or high-numerical aperture objective lenses. PMID:27563909

  3. Interference Confocal Microscope Integrated with Spatial Phase Shifter.

    PubMed

    Wang, Weibo; Gu, Kang; You, Xiaoyu; Tan, Jiubin; Liu, Jian

    2016-08-24

    We present an interference confocal microscope (ICM) with a new single-body four-step simultaneous phase-shifter device designed to obtain high immunity to vibration. The proposed ICM combines the respective advantages of simultaneous phase shifting interferometry and bipolar differential confocal microscopy to obtain high axis resolution, large dynamic range, and reduce the sensitivity to vibration and reflectance disturbance seamlessly. A compact single body spatial phase shifter is added to capture four phase-shifted interference signals simultaneously without time delay and construct a stable and space-saving simplified interference confocal microscope system. The test result can be obtained by combining the interference phase response and the bipolar property of differential confocal microscopy without phase unwrapping. Experiments prove that the proposed microscope is capable of providing stable measurements with 1 nm of axial depth resolution for either low- or high-numerical aperture objective lenses.

  4. LTCC Phase Shifters Based on Tunable Ferroelectric Composite Thick Films

    NASA Astrophysics Data System (ADS)

    Nikfalazar, M.; Kohler, C.; Heunisch, A.; Wiens, A.; Zheng, Y.; Schulz, B.; Mikolajek, M.; Sohrabi, M.; Rabe, T.; Binder, J. R.; Jakoby, R.

    2015-11-01

    This paper presents, the investigation of tunable components based on LTCC technology, implementing ferroelectric tunable thick-film dielectric. The tunable loaded line phase shifters are fabricated with metal-insulator-metal (MIM) varactors to demonstrate the capabilities of this method for packaging of the tunable components. The MIM varactors consist of one tunable dielectric paste layer that is printed between two silver layers. The tunable ferroelectric paste is optimized for LTCC sintering temperature around 850°C. The phase shifters are fabricated in two different process. They were achieved a figure of merit of 24°/dB (phase shift 192°) at 3 GHz and 18°/dB (phase shift 98°) at 4.4 GHz by using seven unit cells that each unit cell consisting of two MIM varactors.

  5. Innovative phase shifter for pulse tube operating below 10 K

    NASA Astrophysics Data System (ADS)

    Duval, Jean-Marc; Charles, Ivan; Daniel, Christophe; André, Jérôme

    2016-09-01

    Stirling type pulse tubes are classically based on the use of an inertance phase shifter to optimize their cooling power. The limitations of the phase shifting capabilities of these inertances have been pointed out in various studies. These limitations are particularly critical for low temperature operation, typically below about 50 K. An innovative phase shifter using an inertance tube filled with liquid, or fluid with high density or low viscosity, and separated by a sealed metallic diaphragm has been conceived and tested. This device has been characterized and validated on a dedicated test bench. Operation on a 50-80 K pulse tube cooler and on a low temperature (below 8 K) pulse tube cooler have been demonstrated and have validated the device in operation. These developments open the door for efficient and compact low temperature Stirling type pulse tube coolers. The possibility of long life operation has been experimentally verified and a design for space applications is proposed.

  6. Broadband opto-mechanical phase shifter for photonic integrated circuits

    NASA Astrophysics Data System (ADS)

    Guo, Xiang; Zou, Chang-Ling; Ren, Xi-Feng; Sun, Fang-Wen; Guo, Guang-Can

    2012-08-01

    A broadband opto-mechanical phase shifter for photonic integrated circuits is proposed and numerically investigated. The structure consists of a mode-carrying waveguide and a deformable non-mode-carrying nanostring, which are parallel with each other. Since the nanostring can be deflected by the optical gradient force between the waveguide and the nanostring, the effective refractive indices of the waveguide will be changed and a phase shift will be generated. The phase shift under different geometry sizes, launched powers and boundary conditions are calculated and the dynamical properties as well as the thermal noise's effect are also discussed. It is demonstrated that a π phase shift can be realized with only about 0.64 mW launched power and 50 μm long nanostring. The proposed phase shifter may find potential usage in future investigation of photonic integrated circuits.

  7. High-level aminoglycoside resistant enterococci isolated from swine.

    PubMed Central

    Jackson, C. R.; Fedorka-Cray, P. J.; Barrett, J. B.; Ladely, S. R.

    2005-01-01

    Approximately 42% (187/444) of swine enterococci collected between the years 1999 and 2000 exhibited high-level resistance to gentamicin (MIC > or =500 microg/ml), kanamycin (MIC > or =500 microg/ml), or streptomycin (MIC > or =1000 microg/ml). Eight aminoglycoside resistance genes were detected using PCR, most frequently ant(6)-Ia and aac(6')-Ii from Enterococcus faecium. Twenty-four per cent (45/187) of total high-level aminoglycoside-resistant isolates and 26% (4/15) of isolates resistant to high levels of all three antimicrobials were negative for all genes tested. These data suggest that enterococci isolated from swine contain diverse and possibly unidentified aminoglycoside resistance genes. PMID:15816164

  8. High-level aminoglycoside resistant enterococci isolated from swine.

    PubMed

    Jackson, C R; Fedorka-Cray, P J; Barrett, J B; Ladely, S R

    2005-04-01

    Approximately 42% (187/444) of swine enterococci collected between the years 1999 and 2000 exhibited high-level resistance to gentamicin (MIC > or =500 microg/ml), kanamycin (MIC > or =500 microg/ml), or streptomycin (MIC > or =1000 microg/ml). Eight aminoglycoside resistance genes were detected using PCR, most frequently ant(6)-Ia and aac(6')-Ii from Enterococcus faecium. Twenty-four per cent (45/187) of total high-level aminoglycoside-resistant isolates and 26% (4/15) of isolates resistant to high levels of all three antimicrobials were negative for all genes tested. These data suggest that enterococci isolated from swine contain diverse and possibly unidentified aminoglycoside resistance genes.

  9. A permanent magnet electron beam phase-shifter

    NASA Astrophysics Data System (ADS)

    Novikov, G. A.; Ermakov, A. N.; Pakhomov, N. I.; Semyachkin, V. K.; Shvedunov, V. I.; Skachkov, V. S.; Tyurin, S. A.

    2004-05-01

    We describe here the design and construction of a permanent magnet-based electron beam phase-shifter now operating in our 70 MeV Race-Track Microtron (P. Lucas, S. Webber (Eds.), Proceedings of the 2001 Particle Accelerator Conference, Vol. 4, IEEE, Piscataway, NJ, 2001, p. 2596; L. Gennary (Ed.), Proceedings of the 1995 Particle Accelerator Conference, Vol. 2, IEEE, Piscataway, NJ, 1996, p. 807).

  10. Searching for new green wavelength shifters in polystyrene

    SciTech Connect

    Pla-Dalmau, A.; Foster, G.W.; Zhang, G.

    1993-12-01

    A series of commercially available fluorescent compounds was tested as wavelength shifters in polystyrene for the tile/fiber SDC calorimeter. The objective was to find a green-fluorescing compound with short decay time (3--7 ns). Transmittance, fluorescence, and decay time measurements were performed in order to characterize each compound in polystyrene. These samples were also studies for radiation-induced damage.

  11. Ferrite Phase Shifters Using Stress Insensitive Materials. Phase 1

    DTIC Science & Technology

    1992-06-11

    PROGRAM OBJECTIVES 1.3 PROGRAM TECHNICAL TASKS (PHASE I) 2.0 BACKGROUND DISCUSSION 2.1 REMANENT STATE FERRITE PHASERS 2.2 REMANENT MAGNETIZATION 2.3... MAGNETIZATION AND MAGNETOSTRICTION 2.1 REMANENT STATE FERRITE PHASERS Microwave ferrite digital phase shifters utilize ferrite toroidal structures and the...The insertion phase length of the structure is dependent on the remanent magnetization of the ferrite (see the hysteresis loop shown in Figure 2-4

  12. Measuring Resistance to Change at the Within-Session Level

    ERIC Educational Resources Information Center

    Tonneau, Francois; Rios, Americo; Cabrera, Felipe

    2006-01-01

    Resistance to change is often studied by measuring response rate in various components of a multiple schedule. Response rate in each component is normalized (that is, divided by its baseline level) and then log-transformed. Differential resistance to change is demonstrated if the normalized, log-transformed response rate in one component decreases…

  13. Dependence of resistivity on the doping level of polycrystalline silicon

    NASA Technical Reports Server (NTRS)

    Fripp, A. L.

    1975-01-01

    The electrical resistivity of polycrystalline silicon films has been studied as a function of doping concentration and heat treatment. The films were grown by the chemical vapor decomposition of silane on oxidized silicon wafers. The resistivity of the as-deposited films was widely scattered but independent of dopant atom concentration at the lightly doped levels and was strong function of dopant level in the more heavily doped regions. Postdeposition heat treatments in an oxidizing atmosphere remove scatter in the data. The resultant resistivity for dopant levels less than 10 to the 16th atoms/per cu cm was approximately equal to that of intrinsic silicon. In the next 2 orders of magnitude increase in dopant level, the resistivity dropped 6 orders of magnitude. A model, based on high dopant atom segregation in the grain boundaries, is proposed to explain the results.

  14. A high-power microwave circular polarizer and its application on phase shifter.

    PubMed

    Shao, Hao; Hu, Yongmei; Chang, Chao; Guo, Letian

    2016-04-01

    A high-power waveguide dual circular polarizer was theoretically designed and proof-of-principle was experimentally tested. It consists of two incident rectangular waveguides with a perpendicular H-plane junction, one circular waveguide with a pair of trapezoidal grooves coupled in E-plane at the top, a spherical crown located at the bottom, and an iris at the perpendicular junction of two rectangular waveguides. When wave incidents at one of the two separated rectangular waveguides, it, respectively, generates a left-hand circular polarized wave or a right-hand circular polarized wave in the circular waveguide. By adding a dumbbell-like metal plug driven with a high speed servomotor, a movable short circuit is formed along the circular waveguide to adjust the output RF phase of the rectangular port, realizing a high-speed high-power phase shifter. The C-band high power microwave (HPM) experiments were carried out, and the power capacity of the HPM polarizer and phase shifter was demonstrated to reach gigawatt level.

  15. Tunable RF photonic phase shifter based on optical DSB modulation and FBG filtering

    NASA Astrophysics Data System (ADS)

    Wei, Yongfeng; Huang, Shanguo; Sun, Kai; Gao, Xinlu; Gu, Wanyi

    2016-01-01

    A broadband RF photonic phase shifter that can achieve the tunable phase shift with little RF amplitude variation is presented. It is based on homodyne mixing technique. The beating between phase-modulated optical carrier and the sidebands can generate RF signal with desired phase shift. Results show the RF phase shifter can achieve a continuous phase shift with low amplitude variation.

  16. Antibiotic resistance shaping multi-level population biology of bacteria

    PubMed Central

    Baquero, Fernando; Tedim, Ana P.; Coque, Teresa M.

    2013-01-01

    Antibiotics have natural functions, mostly involving cell-to-cell signaling networks. The anthropogenic production of antibiotics, and its release in the microbiosphere results in a disturbance of these networks, antibiotic resistance tending to preserve its integrity. The cost of such adaptation is the emergence and dissemination of antibiotic resistance genes, and of all genetic and cellular vehicles in which these genes are located. Selection of the combinations of the different evolutionary units (genes, integrons, transposons, plasmids, cells, communities and microbiomes, hosts) is highly asymmetrical. Each unit of selection is a self-interested entity, exploiting the higher hierarchical unit for its own benefit, but in doing so the higher hierarchical unit might acquire critical traits for its spread because of the exploitation of the lower hierarchical unit. This interactive trade-off shapes the population biology of antibiotic resistance, a composed-complex array of the independent “population biologies.” Antibiotics modify the abundance and the interactive field of each of these units. Antibiotics increase the number and evolvability of “clinical” antibiotic resistance genes, but probably also many other genes with different primary functions but with a resistance phenotype present in the environmental resistome. Antibiotics influence the abundance, modularity, and spread of integrons, transposons, and plasmids, mostly acting on structures present before the antibiotic era. Antibiotics enrich particular bacterial lineages and clones and contribute to local clonalization processes. Antibiotics amplify particular genetic exchange communities sharing antibiotic resistance genes and platforms within microbiomes. In particular human or animal hosts, the microbiomic composition might facilitate the interactions between evolutionary units involved in antibiotic resistance. The understanding of antibiotic resistance implies expanding our knowledge on multi-level

  17. Antibiotic resistance shaping multi-level population biology of bacteria.

    PubMed

    Baquero, Fernando; Tedim, Ana P; Coque, Teresa M

    2013-01-01

    Antibiotics have natural functions, mostly involving cell-to-cell signaling networks. The anthropogenic production of antibiotics, and its release in the microbiosphere results in a disturbance of these networks, antibiotic resistance tending to preserve its integrity. The cost of such adaptation is the emergence and dissemination of antibiotic resistance genes, and of all genetic and cellular vehicles in which these genes are located. Selection of the combinations of the different evolutionary units (genes, integrons, transposons, plasmids, cells, communities and microbiomes, hosts) is highly asymmetrical. Each unit of selection is a self-interested entity, exploiting the higher hierarchical unit for its own benefit, but in doing so the higher hierarchical unit might acquire critical traits for its spread because of the exploitation of the lower hierarchical unit. This interactive trade-off shapes the population biology of antibiotic resistance, a composed-complex array of the independent "population biologies." Antibiotics modify the abundance and the interactive field of each of these units. Antibiotics increase the number and evolvability of "clinical" antibiotic resistance genes, but probably also many other genes with different primary functions but with a resistance phenotype present in the environmental resistome. Antibiotics influence the abundance, modularity, and spread of integrons, transposons, and plasmids, mostly acting on structures present before the antibiotic era. Antibiotics enrich particular bacterial lineages and clones and contribute to local clonalization processes. Antibiotics amplify particular genetic exchange communities sharing antibiotic resistance genes and platforms within microbiomes. In particular human or animal hosts, the microbiomic composition might facilitate the interactions between evolutionary units involved in antibiotic resistance. The understanding of antibiotic resistance implies expanding our knowledge on multi-level

  18. Measuring Resistance to Change at the Within-Session Level

    PubMed Central

    Tonneau, François; Ríos, Américo; Cabrera, Felipe

    2006-01-01

    Resistance to change is often studied by measuring response rate in various components of a multiple schedule. Response rate in each component is normalized (that is, divided by its baseline level) and then log-transformed. Differential resistance to change is demonstrated if the normalized, log-transformed response rate in one component decreases more slowly than in another component. A problem with normalization, however, is that it can produce artifactual results if the relation between baseline level and disruption is not multiplicative. One way to address this issue is to fit specific models of disruption to untransformed response rates and evaluate whether or not a multiplicative model accounts for the data. Here we present such a test of resistance to change, using within-session response patterns in rats as a data base for fitting models of disruption. By analyzing response rate at a within-session level, we were able to confirm a central prediction of the resistance-to-change framework while discarding normalization artifacts as a plausible explanation of our results. PMID:16903495

  19. Measuring resistance to change at the within-session level.

    PubMed

    Tonneau, François; Ríos, Américo; Cabrera, Felipe

    2006-07-01

    Resistance to change is often studied by measuring response rate in various components of a multiple schedule. Response rate in each component is normalized (that is, divided by its baseline level) and then log-transformed. Differential resistance to change is demonstrated if the normalized, log-transformed response rate in one component decreases more slowly than in another component. A problem with normalization, however, is that it can produce artifactual results if the relation between baseline level and disruption is not multiplicative. One way to address this issue is to fit specific models of disruption to untransformed response rates and evaluate whether or not a multiplicative model accounts for the data. Here we present such a test of resistance to change, using within-session response patterns in rats as a data base for fitting models of disruption. By analyzing response rate at a within-session level, we were able to confirm a central prediction of the resistance-to-change framework while discarding normalization artifacts as a plausible explanation of our results.

  20. Magnonic crystals-based tunable microwave phase shifters

    SciTech Connect

    Zhu, Y.; Chi, K. H.; Tsai, C. S.

    2014-07-14

    Tunable microwave phase shifters using magnetostatic backward volume waves in yttrium iron garnet/gadolinium gallium garnet thin film-based one-dimensional (1-D) and two-dimensional (2-D) magnonic crystals (MCs) are reported in this paper. Large differential phase shifts with small insertion loss variations were achieved in the passbands neighboring the bandgaps by tuning of the bias magnetic field. Large phase tuning rates up to 13.48 °/(Oe cm) and 25.9 °/(Oe cm) together with small insertion loss variations of 2.08 dB/cm and 0.97 dB/cm were demonstrated in the 1-D and 2-D MCs, respectively. An excellent agreement between the measured and the calculated results based on Walker's equation was obtained.

  1. Monolithic HTS microwave phase shifter and other devices

    SciTech Connect

    Jackson, C.M.; Kobayashi, J.H.; Guillory, E.B.; Pettiette-Hall, C.; Burch, J.F. )

    1992-08-01

    We describe a monolithic high-temperature superconductor (HTS) phase shifter based on the distributed Josephson inductance (DJI) design integrated monolithically into a 10-GHz microstrip line. This microwave circuit incorporates >1000 HTS rf SQUIDS. Recent data demonstrate the performance of this broadband HTS circuit. We observed phase shifts greater than 150[degrees] in resonant structures, and 20[degrees] in broadband circuits. The nonlinear inductance of the superconducting transmission line can be used for other novel applications, including parametric amplification. A comparison of the DJI circuit to a series array of Josephson elements (used for pulse sharpening) will contrast these two new and exciting nonlinear transmission line circuits. 19 refs., 4 figs., 2 tabs.

  2. A microstrip tunable negative refractive index metamaterial and phase shifter

    NASA Astrophysics Data System (ADS)

    He, P.; Gao, J.; Marinis, C. T.; Parimi, P. V.; Vittoria, C.; Harris, V. G.

    2008-11-01

    A tunable negative refractive index metamaterial and miniature phase shifter have been designed and fabricated in a microstrip configuration for applications in radio frequency integrated circuits. The metamaterial consists of plasmonic copper wires and yttrium iron garnet slabs having a low insertion loss of 5dB at the center of the transmission band. The yttrium iron garnet material enables the magnetic field tuning of the negative refractive index in a dynamic frequency band from 7.0to11.0GHz. The insertion phase can be tuned by 45° continuously by varying the bias field from 3.8to4.6kOe at 9.0GHz.

  3. Efficient, compact and low loss thermo-optic phase shifter in silicon.

    PubMed

    Harris, Nicholas C; Ma, Yangjin; Mower, Jacob; Baehr-Jones, Tom; Englund, Dirk; Hochberg, Michael; Galland, Christophe

    2014-05-05

    We design a resistive heater optimized for efficient and low-loss optical phase modulation in a silicon-on-insulator (SOI) waveguide and characterize the fabricated devices. Modulation is achieved by flowing current perpendicular to a new ridge waveguide geometry. The resistance profile is engineered using different dopant concentrations to obtain localized heat generation and maximize the overlap between the optical mode and the high temperature regions of the structure, while simultaneously minimizing optical loss due to free-carrier absorption. A 61.6 μm long phase shifter was fabricated in a CMOS process with oxide cladding and two metal layers. The device features a phase-shifting efficiency of 24.77 ± 0.43 mW/π and a -3 dB modulation bandwidth of 130.0 ± 5.59 kHz; the insertion loss measured for 21 devices across an 8-inch wafer was only 0.23 ± 0.13 dB. Considering the prospect of densely integrated photonic circuits, we also quantify the separation necessary to isolate thermo-optic devices in the standard 220 nm SOI platform.

  4. RF MEMS Phase Shifters and their Application in Phase Array Antennas

    NASA Technical Reports Server (NTRS)

    Scardelletti, Maximilian; Ponchak, George E.; Zaman, Afroz J.; Lee, Richard Q.

    2005-01-01

    Electronically scanned arrays are required for space based radars that are capable of tracking multiple robots, rovers, or other assets simultaneously and for beam-hopping communication systems between the various assets. ^Traditionally, these phased array antennas used GaAs Monolithic Microwave Integrated Circuit (MMIC) phase shifters, power amplifiers, and low noise amplifiers to amplify and steer the beam, but the development of RF MEMS switches over the past ten years has enabled system designers to consider replacing the GaAs MMIC phase shifters with RF Micro-Electro Mechanical System (MEMS) phase shifters. In this paper, the implication of replacing the relatively high loss GaAs MMICs with low loss MEMS phase shifters is investigated.

  5. Design for steering accuracy in antenna arrays using shared optical phase shifters

    NASA Technical Reports Server (NTRS)

    Kam, Moshe; Herczfeld, Peter R.; Wilcox, Jeffrey

    1989-01-01

    Uniform linear phased arrays where many radiating elements share a relatively small number of phase shifters are investigated. Such architectures arise in arrays which derive the time delays in the signal paths from a small group of independent phase shifters. In particular, a true time-delay device which has been suggested recently for optically controlled arrays is used as the basic phase shifter. Different architectures, viz. alternative procedures of deriving the necessary time delay for each antenna in the face of phase-shifter inaccuracies, are examined. The variance of the steered beam's direction is used as the performance criterion. The direction-optimal architecture is obtained by means of quadratic programming, and is shown not to be unique. The nonuniqueness of the optimal architecture is exploited to improve other characteristics of the array's beam shape, and the optimal solution is shown to compare favorably with a suboptimal interleaved solution which is easier to implement.

  6. Advances in Scanning Reflectarray Antennas Based on Ferroelectric Thin Film Phase Shifters for Deep Space Communications

    NASA Technical Reports Server (NTRS)

    Romanofsky, Robert R.

    2007-01-01

    Though there are a few examples of scanning phased array antennas that have flown successfully in space, the quest for low-cost, high-efficiency, large aperture microwave phased arrays continues. Fixed and mobile applications that may be part of a heterogeneous exploration communication architecture will benefit from the agile (rapid) beam steering and graceful degradation afforded by phased array antennas. The reflectarray promises greater efficiency and economy compared to directly-radiating varieties. Implementing a practical scanning version has proven elusive. The ferroelectric reflectarray, under development and described herein, involves phase shifters based on coupled microstrip patterned on Ba(x)Sr(1-x)TiO3 films, that were laser ablated onto LaAlO3 substrates. These devices outperform their semiconductor counterparts from X- through and K-band frequencies. There are special issues associated with the implementation of a scanning reflectarray antenna, especially one realized with thin film ferroelectric phase shifters. This paper will discuss these issues which include: relevance of phase shifter loss; modulo 2(pi) effects and phase shifter transient effects on bit error rate; scattering from the ground plane; presentation of a novel hybrid ferroelectric-semiconductor phase shifter; and the effect of mild radiation exposure on phase shifter performance.

  7. Wavelength Shifters and Interactions of EDTA with Acrylic & LAB

    NASA Astrophysics Data System (ADS)

    Mohan, Yuvraj; SNO+ Collaboration

    2014-09-01

    The SNO + experiment, an upgrade to the Sudbury Neutrino Observatory, will use linear alkyl-benzene (LAB) liquid scintillator to probe new physics, including 0 νββ decay. Event detection efficiency is heavily affected by radioactive backgrounds, two sources being Rn-222 and Po-210 daughters, some of which has become embedded in the SNO + acrylic vessel after years underground. The leading candidate for polonium leaching is Ethylenediaminetetraacetic acid (EDTA). Before deployment on-site, EDTA's effects on the mechanical integrity of acrylic must be determined. It also must not be soluble in LAB or must be removed before scintillator fill of the vessel, as its presence would result in reduced light yield due to scattering. It was found that EDTA had negligible effects on the Young's Modulus of acrylic. EDTA is also slightly soluble in LAB, but can be completely removed by rinsing with water. Additionally, the study of the light yield and alpha/beta timing profiles of two wavelength shifters - bisMSB and perylene - is critical to determining which should be added to the 0 νββ isotope (tellurium) LAB cocktail. Small-scale results hint that perylene might be better, but this is being confirmed with larger-scale tests. The SNO + experiment, an upgrade to the Sudbury Neutrino Observatory, will use linear alkyl-benzene (LAB) liquid scintillator to probe new physics, including 0 νββ decay. Event detection efficiency is heavily affected by radioactive backgrounds, two sources being Rn-222 and Po-210 daughters, some of which has become embedded in the SNO + acrylic vessel after years underground. The leading candidate for polonium leaching is Ethylenediaminetetraacetic acid (EDTA). Before deployment on-site, EDTA's effects on the mechanical integrity of acrylic must be determined. It also must not be soluble in LAB or must be removed before scintillator fill of the vessel, as its presence would result in reduced light yield due to scattering. It was found that EDTA

  8. Transient - Photoresistance Spectroscopy of Deep Levels in High Resistivity Semiconductors

    NASA Astrophysics Data System (ADS)

    Seabaugh, Alan Carter

    A new photoinduced transient-resistance technique is proposed and examined for use in characterizing high -resistivity, short-lifetime semiconductors. In this technique, termed photoresistance deep-level transient spectroscopy (PR-DLTS), an optical pulse is used to generate excess carriers which are trapped by deep levels in the material. The ac resistance of the specimen is monitored, and the resistance transient which occurs after the illumination ends is signal processed in the same way as the capacitance transient in DLTS. A phenomenological model of the phototransient is used to derive an expression for the decay transient. Two limiting forms for the transient are predicted depending upon whether the emitted carriers are collected at the device contacts, or recombine in the bulk before being collected. In order to test this model, several methods for distinguishing between the predicted decays of the form exp(-(lamda)t) and (lamda)exp(-(lamda)t) were developed ((lamda) is the reciprocal time constant for the decay). The measured results are consistent with the predictions of the model, but an 'ideal' sample has not been found to fully test the predictions. On Au-doped Si, excellent agreement between published emission rates for the Au-acceptor and the apparent emission rates measured by PR-DLTS is found. In addition, PR-DLTS data for the Cr-related deep level in semi-insulating GaAs is consistent with published DLTS results on conducting GaAs. Comparison of the PR-DLTS technique with the dc current-transient technique, photoinduced transient spectroscopy (PITS), shows that the two techniques are sensitive to the same trapping/detrapping phenomena. Finally, the results of a comparative study of commercial semi-insulating GaAs are reported. Nineteen specimens from ten suppliers were examined using the PR -DLTS technique, including material grown by the horizontal Bridgman (HB) and liquid-encapsulated Czochralski (LEC) technique, both with and without Cr

  9. A novel high power X-band ferrite phase shifter

    NASA Astrophysics Data System (ADS)

    Deng, G. J.; Huang, W. H.; Li, J. W.; Ba, T.; Guo, L. T.; Jiang, Y.

    2017-01-01

    A novel high power X-band ferrite phase shifter (PS) employing the structure of several waveguides connected in parallel is proposed. Each of the waveguides is a phase shift unit utilizing a dual-toroid structure. First, the phase shift unit is designed, manufactured, and tested. The results indicate that the power capacity reaches 115 kW. At this power, the maximum magnetic field strength of ferrite is 7.9 kA/m, beyond which the nonlinear effect of ferrite will occur. On this basis, the PS that consists of four units connected in parallel is designed. According to the threshold of ferrite, the power capacity of the PS can theoretically reach 430 kW. Limited by the maximum output power of the microwave source, the preliminary high-power test results demonstrate that the PS can operate properly at 270 kW. The PS exhibits an insertion loss of 0.82 dB and a maximum differential phase shift of approximately 300° at 9.3 GHz. The return loss of the PS is more than 16 dB from 9.0 to 9.5 GHz.

  10. A novel high power X-band ferrite phase shifter.

    PubMed

    Deng, G J; Huang, W H; Li, J W; Ba, T; Guo, L T; Jiang, Y

    2017-01-01

    A novel high power X-band ferrite phase shifter (PS) employing the structure of several waveguides connected in parallel is proposed. Each of the waveguides is a phase shift unit utilizing a dual-toroid structure. First, the phase shift unit is designed, manufactured, and tested. The results indicate that the power capacity reaches 115 kW. At this power, the maximum magnetic field strength of ferrite is 7.9 kA/m, beyond which the nonlinear effect of ferrite will occur. On this basis, the PS that consists of four units connected in parallel is designed. According to the threshold of ferrite, the power capacity of the PS can theoretically reach 430 kW. Limited by the maximum output power of the microwave source, the preliminary high-power test results demonstrate that the PS can operate properly at 270 kW. The PS exhibits an insertion loss of 0.82 dB and a maximum differential phase shift of approximately 300° at 9.3 GHz. The return loss of the PS is more than 16 dB from 9.0 to 9.5 GHz.

  11. Constant volume gas cell optical phase-shifter

    DOEpatents

    Phillion, Donald W.

    2002-01-01

    A constant volume gas cell optical phase-shifter, particularly applicable for phase-shifting interferometry, contains a sealed volume of atmospheric gas at a pressure somewhat different than atmospheric. An optical window is present at each end of the cell, and as the length of the cell is changed, the optical path length of a laser beam traversing the cell changes. The cell comprises movable coaxial tubes with seals and a volume equalizing opening. Because the cell is constant volume, the pressure, temperature, and density of the contained gas do not change as the cell changes length. This produces an exactly linear relationship between the change in the length of the gas cell and the change in optical phase of the laser beam traversing it. Because the refractive index difference between the gas inside and the atmosphere outside is very much the same, a large motion must be made to change the optical phase by the small fraction of a wavelength that is required by phase-shifting interferometry for its phase step. This motion can be made to great fractional accuracy.

  12. Urinary Tract Physiological Conditions Promote Ciprofloxacin Resistance in Low-Level-Quinolone-Resistant Escherichia coli.

    PubMed

    Martín-Gutiérrez, Guillermo; Rodríguez-Beltrán, Jerónimo; Rodríguez-Martínez, José Manuel; Costas, Coloma; Aznar, Javier; Pascual, Álvaro; Blázquez, Jesús

    2016-07-01

    Escherichia coli isolates carrying chromosomally encoded low-level-quinolone-resistant (LLQR) determinants are frequently found in urinary tract infections (UTIs). LLQR mutations are considered the first step in the evolutionary pathway producing high-level fluoroquinolone resistance. Therefore, their evolution and dissemination might influence the outcome of fluoroquinolone treatments of UTI. Previous studies support the notion that low urine pH decreases susceptibility to ciprofloxacin (CIP) in E. coli However, the effect of the urinary tract physiological parameters on the activity of ciprofloxacin against LLQR E. coli strains has received little attention. We have studied the activity of ciprofloxacin under physiological urinary tract conditions against a set of well-characterized isogenic E. coli derivatives carrying the most prevalent chromosomal mutations (ΔmarR, gyrA-S83L, gyrA-D87N, and parC-S80R and some combinations). The results presented here demonstrate that all the LLQR strains studied became resistant to ciprofloxacin (according to CLSI guidelines) under physiological conditions whereas the control strain lacking LLQR mutations did not. Moreover, the survival of some LLQR E. coli variants increased up to 100-fold after challenge with a high concentration of ciprofloxacin under UTI conditions compared to the results seen with Mueller-Hinton broth. These selective conditions could explain the high prevalence of LLQR mutations in E. coli Furthermore, our data strongly suggest that recommended methods for MIC determination produce poor estimations of CIP activity against LLQR E. coli in UTIs.

  13. Urinary Tract Physiological Conditions Promote Ciprofloxacin Resistance in Low-Level-Quinolone-Resistant Escherichia coli

    PubMed Central

    Rodríguez-Martínez, José Manuel; Costas, Coloma; Aznar, Javier; Pascual, Álvaro

    2016-01-01

    Escherichia coli isolates carrying chromosomally encoded low-level-quinolone-resistant (LLQR) determinants are frequently found in urinary tract infections (UTIs). LLQR mutations are considered the first step in the evolutionary pathway producing high-level fluoroquinolone resistance. Therefore, their evolution and dissemination might influence the outcome of fluoroquinolone treatments of UTI. Previous studies support the notion that low urine pH decreases susceptibility to ciprofloxacin (CIP) in E. coli. However, the effect of the urinary tract physiological parameters on the activity of ciprofloxacin against LLQR E. coli strains has received little attention. We have studied the activity of ciprofloxacin under physiological urinary tract conditions against a set of well-characterized isogenic E. coli derivatives carrying the most prevalent chromosomal mutations (ΔmarR, gyrA-S83L, gyrA-D87N, and parC-S80R and some combinations). The results presented here demonstrate that all the LLQR strains studied became resistant to ciprofloxacin (according to CLSI guidelines) under physiological conditions whereas the control strain lacking LLQR mutations did not. Moreover, the survival of some LLQR E. coli variants increased up to 100-fold after challenge with a high concentration of ciprofloxacin under UTI conditions compared to the results seen with Mueller-Hinton broth. These selective conditions could explain the high prevalence of LLQR mutations in E. coli. Furthermore, our data strongly suggest that recommended methods for MIC determination produce poor estimations of CIP activity against LLQR E. coli in UTIs. PMID:27139482

  14. High-level tetracycline resistant Neisseria gonorrhoeae isolated in Portugal.

    PubMed

    Ferreira, E; Louro, D; Gomes, J P; Catry, M A; Pato, M V

    1997-05-01

    The first high-level tetracycline resistance (MIC > or = 16 mg/l) isolates of Neisseria gonorrhoeae (TRNG) were reported in 1990 from patients attending a Sexual Transmitted Disease (STD) Center in Lisbon. The TRNG prevalence was 4% in 1991, 5.3% in 1992 and 10,8% in 1994, exploding to 52.2% in 1995. The tet M determinant was evaluated by PCR. The digests of PCRP using HpaII produced the restriction pattern 2 for all the strains, except one (pattern 3). 78.3% of the TRNG strains were beta-lactamase producers and the 4.5 MDa penicillinase plasmid was the dominant (83%), 90% and 93.3% of the TRNG strains belonged to the auxotype NR and to the serogroup IA, respectively. The IA-8/NR class represented 58.3% of the TRNG isolates, suggesting a clonal spreading.

  15. Tunable ferroelectric meta-material phase shifter embedded inside low temperature co-fired ceramics (LTCC)

    NASA Astrophysics Data System (ADS)

    Tork, Hossam S.

    This dissertation describes electrically tunable microwave devices utilizing low temperature co-fired ceramics (LTCC) and thick film via filled with the ferroelectric materials barium strontium titanate (BST) and barium zirconate titanate (BZT). Tunable ferroelectric capacitors, zero meta-material phase shifters, and tunable meta-material phase shifters are presented. Microwave phase shifters have many applications in microwave devices. They are essential components for active and passive phased array antennas and their most common use is in scanning phased array antennas. They are used in synthetic aperture radars (SAR), low earth orbit (LEO) communication satellites, collision warning radars, and intelligent vehicle highway systems (IVHS), in addition to various other applications. Tunable ferroelectric materials have been investigated, since they offer the possibility of lowering the total cost of phased arrays. Two of the most promising ferroelectric materials in microwave applications are BST and BZT. The proposed design and implementation in this research introduce new types of tunable meta-material phase shifters embedded inside LTCC, which use BST and BZT as capacitive tunable dielectric material controlled by changing the applied voltage. This phase shifter has the advantages of meta-material structures, which produce little phase error and compensation while having the simultaneous advantage of using LTCC technology for embedding passive components that improve signal integrity (several signal lines, power planes, and ground planes) by using different processes like via filling, screen printing, laminating and firing that can be produced in compact sizes at a low cost. The via filling technique was used to build tunable BST, BZT ferroelectric material capacitors to control phase shift. Finally, The use of the proposed ferroelectric meta-material phase shifter improves phase shifter performance by reducing insertion loss in both transmitting and receiving

  16. A compact, low-loss, tunable phase shifter on defect mitigated dielectrics up to 40 GHz

    NASA Astrophysics Data System (ADS)

    Orloff, Nathan; Long, Christian; Lu, Xifeng; Nair, Hari; Dawley, Natalie; Schlom, Darrell; Booth, James

    With the emergence of the internet-of-things and increased connectivity of modern commerce, consumers have driven demand for wireless spectrum beyond current capacity and infrastructure capabilities. One way the telecommunications industry is addressing this problem is by pushing front-end electronics to higher frequencies, introducing carrier aggregation schemes, and developing spectrum-sharing techniques. Some of these solutions require frequency agile components that are vastly different from what is in today's marketplace. Perhaps the most basic and ubiquitous component in front-end electronics is the phase shifter. Phase shifters are particularly important for compact beam-forming antennas that may soon appear in commercial technology. Here, we demonstrate a compact, tunable phase shifter with very low insertion loss up to 40 GHz on a defect mitigated tunable dielectric. We demonstrate performance compared to barium-doped strontium titanate phase shifters. Such phase shifters could potentially meet the stringent size and performance characteristics demanded by telecommunications industry, readily facilitating massive multiple-input multiple-output antennas in the next-generation of mobile handsets.

  17. Improving dye laser efficiency with uv absorbers and wavelength shifters. Final report

    SciTech Connect

    Matheson, K L; Thorne, J M

    1981-01-01

    The nonuniform heating in flashlamp pumped dye lasers forms refractive index gradients in the dye solution. These gradients distort the wavefront of the laser beam resulting in limited output power, limited pulse repetition rate, and limited attainable linewidth. The theorectical bases for using uv absorbers and wavelength shifters to eliminate light of detrimental wavelengths and thereby improve dye laser efficiency are described, and the results of experiments for evaluating 12 uv absorbers and 12 wavelength filters for use as possible pump light filters are presented. These experiments showed that the appropriate uv absorber or wavelength shifter to be used with a given laser dye is based on the absorption spectrum of the dye. If a uv absorber is needed, then the compound should be chosen so that its long wavelength absorption peak is just to the short wavelength side of the absorption peaks of the laser dye. If a wavelength shifter is needed, then the compound should be chosen so that there is maximum overlap between the fluorescence spectrum of the shifter and the absorption spectrum of the dye. Tabulated data are presented which can be used to selected protectors and shifters for specific dyes. (LCL)

  18. Development of high precision digital driver of acoustic-optical frequency shifter for ROG

    NASA Astrophysics Data System (ADS)

    Zhang, Rong; Kong, Mei; Xu, Yameng

    2016-10-01

    We develop a high precision digital driver of the acoustic-optical frequency shifter (AOFS) based on the parallel direct digital synthesizer (DDS) technology. We use an atomic clock as the phase-locked loop (PLL) reference clock, and the PLL is realized by a dual digital phase-locked loop. A DDS sampling clock up to 320 MHz with a frequency stability as low as 10-12 Hz is obtained. By constructing the RF signal measurement system, it is measured that the frequency output range of the AOFS-driver is 52-58 MHz, the center frequency of the band-pass filter is 55 MHz, the ripple in the band is less than 1 dB@3MHz, the single channel output power is up to 0.3 W, the frequency stability is 1 ppb (1 hour duration), and the frequency-shift precision is 0.1 Hz. The obtained frequency stability has two orders of improvement compared to that of the analog AOFS-drivers. For the designed binary frequency shift keying (2-FSK) and binary phase shift keying (2-PSK) modulation system, the demodulating frequency of the input TTL synchronous level signal is up to 10 kHz. The designed digital-bus coding/decoding system is compatible with many conventional digital bus protocols. It can interface with the ROG signal detecting software through the integrated drive electronics (IDE) and exchange data with the two DDS frequency-shift channels through the signal detecting software.

  19. Comments on ferrite phase shifter configurations for the millimeter wave region

    NASA Astrophysics Data System (ADS)

    Reuss, M. L., Jr.

    1982-09-01

    In the microwave region of the electromagnetic spectrum, electronically controllable ferrite phase shifters have demonstrated their value as components and as control elements for switches and attenuators. As the need for control components operating in the lower millimeter wave region increases, it is a reasonable approach to scale successful microwave ferrite configurations into the lower millimeter wave region (30 GHz to 140 GHz). However, many problems are encountered when attempting to scale efficient microwave ferrite configurations, particularly latching ferrite configurations, into the millimeter wave region. It is the objective of this report to review several ferrite configurations with the intent that consideration of these configurations may stimulate development of practical millimeter wave configurations. Ferrite phase shifter configurations that will be the subject of comment include the toroidal (dual slab), dual mode, Bush-Reggia-Spencer, and single slab configurations. Comments are also presented on a circulator used as a phase shifter.

  20. Design and modeling of compact phase shifter based on graphene electro-refraction effects

    NASA Astrophysics Data System (ADS)

    Hu, Xiao; Wang, Jian

    2017-03-01

    By exploiting the electro-refraction effect of graphene, we present a graphene-based compact phase shifter. The waveguide structure consists of a silica substrate, a high index silicon (Si) vertical slot waveguide, a Si3N4 dielectric spacer, two graphene layers, and two metal electrodes. The phase shifter performance is comprehensively studied in terms of working range, insertion loss, bandwidth, and V2π for transverse magnetic and transverse electric modes. The obtained results show a linear relationship between the applied voltage and phase shift.

  1. Figures of merit for microwave photonic phase shifters based on semiconductor optical amplifiers.

    PubMed

    Sancho, Juan; Lloret, Juan; Gasulla, Ivana; Sales, Salvador; Capmany, José

    2012-05-07

    We theoretically and experimentally compare the performance of two fully tunable phase shifter structures based on semiconductor optical amplifiers (SOA) by means of several figures of merit common to microwave photonic systems. A single SOA stage followed by a tailored notch filter is compared with a cascaded implementation comprising three SOA-based phase shifter stages. Attention is focused on the assessment of the RF net gain, noise figure and nonlinear distortion. Recommendations on the performance optimization of this sort of approaches are detailed.

  2. Liquid crystal terahertz phase shifters with functional indium-tin-oxide nanostructures for biasing and alignment

    NASA Astrophysics Data System (ADS)

    Yang, Chan-Shan; Tang, Tsung-Ta; Pan, Ru-Pin; Yu, Peichen; Pan, Ci-Ling

    2014-04-01

    Indium Tin Oxide (ITO) nanowhiskers (NWhs) obliquely evaporated by electron-beam glancing-angle deposition can serve simultaneously as transparent electrodes and alignment layer for liquid crystal (LC) devices in the terahertz (THz) frequency range. To demonstrate, we constructed a THz LC phase shifter with ITO NWhs. Phase shift exceeding π/2 at 1.0 THz was achieved in a ˜517 μm-thick cell. The phase shifter exhibits high transmittance (˜78%). The driving voltage required for quarter-wave operation is as low as 5.66 V (rms), compatible with complementary metal-oxide-semiconductor (CMOS) and thin-film transistor (TFT) technologies.

  3. Liquid crystal terahertz phase shifters with functional indium-tin-oxide nanostructures for biasing and alignment

    SciTech Connect

    Yang, Chan-Shan; Tang, Tsung-Ta; Pan, Ru-Pin; Yu, Peichen; Pan, Ci-Ling

    2014-04-07

    Indium Tin Oxide (ITO) nanowhiskers (NWhs) obliquely evaporated by electron-beam glancing-angle deposition can serve simultaneously as transparent electrodes and alignment layer for liquid crystal (LC) devices in the terahertz (THz) frequency range. To demonstrate, we constructed a THz LC phase shifter with ITO NWhs. Phase shift exceeding π/2 at 1.0 THz was achieved in a ∼517 μm-thick cell. The phase shifter exhibits high transmittance (∼78%). The driving voltage required for quarter-wave operation is as low as 5.66 V (rms), compatible with complementary metal-oxide-semiconductor (CMOS) and thin-film transistor (TFT) technologies.

  4. Glyphosate-Resistant Parthenium hysterophorus in the Caribbean Islands: Non Target Site Resistance and Target Site Resistance in Relation to Resistance Levels

    PubMed Central

    Bracamonte, Enzo; Fernández-Moreno, Pablo T.; Barro, Francisco; De Prado, Rafael

    2016-01-01

    Glyphosate has been the most intensely herbicide used worldwide for decades, and continues to be a single tool for controlling weeds in woody crops. However, the adoption of this herbicide in a wide range of culture systems has led to the emergence of resistant weeds. Glyphosate has been widely used primarily on citrus in the Caribbean area, but a study of resistance in the Caribbean islands of Cuba and the Dominican Republic has never been carried out. Unfortunately, Parthenium hysterophorus has developed glyphosate-resistance in both islands, independently. The resistance level and mechanisms of different P. hysterophorus accessions (three collected in Cuba (Cu-R) and four collected in the Dominican Republic (Do-R) have been studied under greenhouse and laboratory conditions. In in vivo assays (glyphosate dose causing 50% reduction in above-ground vegetative biomass and survival), the resistance factor levels showed susceptible accessions (Cu-S ≥ Do-S), low-resistance accessions (Cu-R3 < Do-R4), medium-resistance accessions (Do-R3 < Cu-R2 < Do-R2) and high-resistance accessions (Do-R1 < Cu-R1). In addition, the resistance factor levels were similar to those found in the shikimic acid accumulation at 1000 μM of glyphosate (Cu-R1 ≥ Do-R1 > Do-R2 > Cu-R2 > Do-R3 > Do-R4 > Cu-R3 >> Cu-S ≥ Do-S). Glyphosate was degraded to aminomethylphosphonic acid, glyoxylate and sarcosine by >88% in resistant accessions except in Cu-R3 and Do-R4 resistant accessions (51.12 and 44.21, respectively), whereas a little glyphosate (<9.32%) was degraded in both susceptible accessions at 96 h after treatment. There were significant differences between P. hysterophorus accessions in the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) activity enzyme with and without different glyphosate rates. The R accessions showed values of between 0.026 and 0.21 μmol μg−1 TSP protein min−1 basal EPSPS activity values with respect to the S (0.024 and 0.025) accessions. The same trend

  5. Glyphosate-Resistant Parthenium hysterophorus in the Caribbean Islands: Non Target Site Resistance and Target Site Resistance in Relation to Resistance Levels.

    PubMed

    Bracamonte, Enzo; Fernández-Moreno, Pablo T; Barro, Francisco; De Prado, Rafael

    2016-01-01

    Glyphosate has been the most intensely herbicide used worldwide for decades, and continues to be a single tool for controlling weeds in woody crops. However, the adoption of this herbicide in a wide range of culture systems has led to the emergence of resistant weeds. Glyphosate has been widely used primarily on citrus in the Caribbean area, but a study of resistance in the Caribbean islands of Cuba and the Dominican Republic has never been carried out. Unfortunately, Parthenium hysterophorus has developed glyphosate-resistance in both islands, independently. The resistance level and mechanisms of different P. hysterophorus accessions (three collected in Cuba (Cu-R) and four collected in the Dominican Republic (Do-R) have been studied under greenhouse and laboratory conditions. In in vivo assays (glyphosate dose causing 50% reduction in above-ground vegetative biomass and survival), the resistance factor levels showed susceptible accessions (Cu-S ≥ Do-S), low-resistance accessions (Cu-R3 < Do-R4), medium-resistance accessions (Do-R3 < Cu-R2 < Do-R2) and high-resistance accessions (Do-R1 < Cu-R1). In addition, the resistance factor levels were similar to those found in the shikimic acid accumulation at 1000 μM of glyphosate (Cu-R1 ≥ Do-R1 > Do-R2 > Cu-R2 > Do-R3 > Do-R4 > Cu-R3 > Cu-S ≥ Do-S). Glyphosate was degraded to aminomethylphosphonic acid, glyoxylate and sarcosine by >88% in resistant accessions except in Cu-R3 and Do-R4 resistant accessions (51.12 and 44.21, respectively), whereas a little glyphosate (<9.32%) was degraded in both susceptible accessions at 96 h after treatment. There were significant differences between P. hysterophorus accessions in the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) activity enzyme with and without different glyphosate rates. The R accessions showed values of between 0.026 and 0.21 μmol μg(-1) TSP protein min(-1) basal EPSPS activity values with respect to the S (0.024 and 0.025) accessions. The same trend was

  6. Design optimization of liquid scintillator cosmic-ray veto detector with BBQ shifter

    SciTech Connect

    Kruse, H.W.; Egdorf, S.S.; Simmons, D.F.

    1981-10-01

    Certain design characteristics of a liquid scintillator detector for charged cosmic particles, have been studied. These include evaluation of scintillator emission spectra, absorption in various thicknesses of BBQ shifter bars and effective transmission in long lengths of BBQ acrylic. For our BBQ sample, 12.5 mm thick with semicircular shape, the shifted light was transmitted with 2.0 m absorption length.

  7. Integrated nanophotonic frequency shifter on the silicon-organic hybrid (SOH) platform for laser vibrometry

    SciTech Connect

    Lauermann, M.; Weimann, C.; Palmer, R.; Schindler, P. C.; Koeber, S.; Freude, W. Koos, C.; Rembe, C.

    2014-05-27

    We demonstrate a waveguide-based frequency shifter on the silicon photonic platform, enabling frequency shifts up to 10 GHz. The device is realized by silicon-organic hybrid (SOH) integration. Temporal shaping of the drive signal allows the suppression of spurious side-modes by more than 23 dB.

  8. Investigation of Aging Effects from High Voltage Profiles in Ceramic Phase Shifter Materials

    DTIC Science & Technology

    1994-12-01

    for the BSTO-Alumina composites. REFERENCES [1] R.W. Babbitt, T. E. Koscica, and W.E. Drach , "Planar Microwave Electro-optic Phase Shifters...Sources Director»,., For, Monroes, 1 ATTN: AMSRL-EP-M, W. C. Drach 1 AMSRL-EP-M, T. E. Koscica 1 AMSRL-EP-M, R. W. Babbit 25 Authors 11

  9. Distributed electrode Mach-Zehnder modulator with double-pass phase shifters and integrated inductors.

    PubMed

    Gill, D M; Green, W M J; Xiong, C; Rylyakov, A; Schow, C; Proesel, J; Rosenberg, J C; Barwicz, T; Khater, M; Assefa, S; Shank, S M; Reinholm, C; Kiewra, E; Kamlapurkar, S; Vlasov, Y A

    2015-06-29

    A novel high-speed Mach-Zehnder modulator (MZM) fully integrated into a 90 nm CMOS process is presented. The MZM features 'double-pass' optical phase shifter segments, and the first use of integrated inductors in a 'velocity-matched' distributed-electrode configuration.

  10. A Theoretical Model for Thin Film Ferroelectric Coupled Microstripline Phase Shifters

    NASA Technical Reports Server (NTRS)

    Romanofsky, R. R.; Quereshi, A. H.

    2000-01-01

    Novel microwave phase shifters consisting of coupled microstriplines on thin ferroelectric films have been demonstrated recently. A theoretical model useful for predicting the propagation characteristics (insertion phase shift, dielectric loss, impedance, and bandwidth) is presented here. The model is based on a variational solution for line capacitance and coupled strip transmission line theory.

  11. High Levels of Expression of P-glycoprotein/Multidrug Resistance Protein Result in Resistance to Vintafolide.

    PubMed

    Guertin, Amy D; O'Neil, Jennifer; Stoeck, Alexander; Reddy, Joseph A; Cristescu, Razvan; Haines, Brian B; Hinton, Marlene C; Dorton, Ryan; Bloomfield, Alicia; Nelson, Melissa; Vetzel, Marilynn; Lejnine, Serguei; Nebozhyn, Michael; Zhang, Theresa; Loboda, Andrey; Picard, Kristen L; Schmidt, Emmett V; Dussault, Isabelle; Leamon, Christopher P

    2016-08-01

    Targeting surface receptors overexpressed on cancer cells is one way to specifically treat cancer versus normal cells. Vintafolide (EC145), which consists of folate linked to a cytotoxic small molecule, desacetylvinblastine hydrazide (DAVLBH), takes advantage of the overexpression of folate receptor (FR) on cancer cells. Once bound to FR, vintafolide enters the cell by endocytosis, and the reducing environment of the endosome cleaves the linker, releasing DAVLBH to destabilize microtubules. Vintafolide has shown efficacy and improved tolerability compared with DAVLBH in FR-positive preclinical models. As the first FR-targeting drug to reach the clinic, vintafolide has achieved favorable responses in phase II clinical trials in FR-positive ovarian and lung cancer. However, some FR-positive patients in these clinical trials do not respond to vintafolide. We sought to identify potential biomarkers of resistance to aid in the future development of this and other FR-targeting drugs. Here, we confirm that high P-glycoprotein (P-gp) expression was the strongest predictor of resistance to DAVLBH in a panel of 359 cancer cell lines. Furthermore, targeted delivery of DAVLBH via the FR, as in vintafolide, fails to overcome P-gp-mediated efflux of DAVLBH in both in vitro and in vivo preclinical models. Therefore, we suggest that patients whose tumors express high levels of P-gp be excluded from future clinical trials for vintafolide as well as other FR-targeted therapeutics bearing a P-gp substrate. Mol Cancer Ther; 15(8); 1998-2008. ©2016 AACR.

  12. Insecticide resistance in house flies from the United States: Resistance levels and frequency of pyrethroid resistance alleles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although insecticide resistance is a widespread problem for most insect pests, frequently the assessment of resistance occurs over a limited geographic range. Herein we report the first widespread survey of insecticide resistance ever undertaken for the house fly, Musca domestica, a major pest of a...

  13. Broadband Achromatic Phase Shifter for a Nulling Interferometer

    NASA Technical Reports Server (NTRS)

    Bolcar, Matthew R.; Lyon, Richard G.

    2011-01-01

    Nulling interferometry is a technique for imaging exoplanets in which light from the parent star is suppressed using destructive interference. Light from the star is divided into two beams and a phase shift of radians is introduced into one of the beams. When the beams are recombined, they destructively interfere to produce a deep null. For monochromatic light, this is implemented by introducing an optical path difference (OPD) between the two beams equal to lambda/2, where lambda is the wavelength of the light. For broadband light, however, a different phase shift will be introduced at each wavelength and the two beams will not effectively null when recombined. Various techniques have been devised to introduce an achromatic phase shift a phase shift that is uniform across a particular bandwidth. One popular technique is to use a series of dispersive elements to introduce a wavelength-dependent optical path in one or both of the arms of the interferometer. By intelligently choosing the number, material and thickness of a series of glass plates, a nearly uniform, arbitrary phase shift can be introduced between two arms of an interferometer. There are several constraints that make choosing the number, type, and thickness of materials a difficult problem, such as the size of the bandwidth to be nulled. Several solutions have been found for bandwidths on the order of 20 to 30 percent (Delta(lambda)/lambda(sub c)) in the mid-infrared region. However, uniform phase shifts over a larger bandwidth in the visible regime between 480 to 960 nm (67 percent) remain difficult to obtain at the tolerances necessary for exoplanet detection. A configuration of 10 dispersive glass plates was developed to be used as an achromatic phase shifter in nulling interferometry. Five glass plates were placed in each arm of the interferometer and an additional vacuum distance was also included in the second arm of the interferometer. This configuration creates a phase shift of pi radians with

  14. Ranked Levels of Influence Model: Selecting Influence Techniques to Minimize IT Resistance

    PubMed Central

    Bartos, Christa E.; Butler, Brian S.; Crowley, Rebecca S.

    2010-01-01

    Implementation of electronic health records (EHR), particularly computerized physician/provider order entry systems (CPOE), is often met with resistance. Influence presented at the right time, in the right manner, may minimize resistance or at least limit the risk of complete system failure. Combining established theories on power, influence tactics, and resistance, we developed the Ranked Levels of Influence model. Applying it to documented examples of EHR/CPOE failures at Cedars-Sinai and Kaiser Permanente in Hawaii, we evaluated the influence applied, the resistance encountered, and the resulting risk to the system implementation. Using the Ranked Levels of Influence model as a guideline, we demonstrate that these system failures were associated with the use of hard influence tactics that resulted in higher levels of resistance. We suggest that when influence tactics remain at the soft tactics level, the level of resistance stabilizes or de-escalates and the system can be saved. PMID:20176135

  15. PBP 4 Mediates High-Level Resistance to New-Generation Cephalosporins in Staphylococcus aureus

    PubMed Central

    Chan, Liana C.; Gilbert, Aubre; Basuino, Li; da Costa, Thaina M.; Hamilton, Stephanie M.; dos Santos, Katia R.; Chambers, Henry F.

    2016-01-01

    Staphylococcus aureus is an important cause of both hospital- and community-associated methicillin-resistant S. aureus (MRSA) infections worldwide. β-Lactam antibiotics are the drugs of choice to treat S. aureus infections, but resistance to these and other antibiotics make treatment problematic. High-level β-lactam resistance of S. aureus has always been attributed to the horizontally acquired penicillin binding protein 2a (PBP 2a) encoded by the mecA gene. Here, we show that S. aureus can also express high-level resistance to β-lactams, including new-generation broad-spectrum cephalosporins that are active against methicillin-resistant strains, through an uncanonical core genome-encoded penicillin binding protein, PBP 4, a nonessential enzyme previously considered not to be important for staphylococcal β-lactam resistance. Our results show that PBP 4 can mediate high-level resistance to β-lactams. PMID:27067335

  16. De Novo Characterization of Genes That Contribute to High-Level Ciprofloxacin Resistance in Escherichia coli

    PubMed Central

    Tran, Thu; Ran, Qinghong; Ostrer, Lev

    2016-01-01

    Sensitization of resistant bacteria to existing antibiotics depends on the identification of candidate targets whose activities contribute to resistance. Using a transposon insertion library in an Escherichia coli mutant that was 2,000 times less susceptible to ciprofloxacin than its parent and the relative fitness scores, we identified 19 genes that contributed to the acquired ciprofloxacin resistance and mapped the shortest genetic path that increased the antibiotic susceptibility of the resistant bacteria back to a near wild-type level. PMID:27431218

  17. Quantitative resistance level (MIC) of Pasteurella multocida isolated from pigs between 2004 and 2006: national resistance monitoring by the BVL.

    PubMed

    Kaspar, Heike; Schröer, Ulrike; Wallmann, Jürgen

    2007-01-01

    The National Resistance Monitoring of the Federal Office of Consumer Protection and Food Safety (BVL) is to determine the prevalence of resistance of bacterial pathogens from animals using a valid database. From 2004 to 2006, a total of 1,472 Pasteurella multocida strains isolated from pigs with acute respiratory tract diseases was submitted to the BVL and examined. Of these, 1,11 (75.5 %) were included in the study and tested using 24 different antimicrobial substances. The results showed that the resistance level is generally low, with the exception of the substances tetracycline, trimethoprim, and the combination trimethoprim/sulfamethoxazole. It also became clear that resistance data need to be evaluated separately for each of the animal production categories, so that a realistic figure of the current resistance level can be presented. This knowledge provides information about the resistance situation in Germany, and helps deduce the necessary management measures that must be taken to minimize resistance to antibiotics. Furthermore, it provides valuable information that can form the basis for empirical therapy, so that the National Resistance Monitoring makes an important contribution to the safety of food derived from animals and consequently aids the improvement of consumer protection.

  18. PBP2a Mutations Causing High-Level Ceftaroline Resistance in Clinical Methicillin-Resistant Staphylococcus aureus Isolates

    PubMed Central

    Long, S. Wesley; Olsen, Randall J.; Mehta, Shrenik C.; Palzkill, Timothy; Cernoch, Patricia L.; Perez, Katherine K.; Musick, William L.; Rosato, Adriana E.

    2014-01-01

    Ceftaroline is the first member of a novel class of cephalosporins approved for use in the United States. Although prior studies have identified eight ceftaroline-resistant methicillin-resistant Staphylococcus aureus (MRSA) isolates in Europe and Asia with MICs ranging from 4 to 8 mg/liter, high-level resistance to ceftaroline (>32 mg/liter) has not been described in MRSA strains isolated in the United States. We isolated a ceftaroline-resistant (MIC > 32 mg/liter) MRSA strain from the blood of a cystic fibrosis patient and five MRSA strains from the respiratory tract of this patient. Whole-genome sequencing identified two amino acid-altering mutations uniquely present in the ceftaroline-binding pocket of the transpeptidase region of penicillin-binding protein 2a (PBP2a) in ceftaroline-resistant isolates. Biochemical analyses and the study of isogenic mutant strains confirmed that these changes caused ceftaroline resistance. Thus, we identified the molecular mechanism of ceftaroline resistance in the first MRSA strain with high-level ceftaroline resistance isolated in the United States. PMID:25155594

  19. Cracking resistance in steam pipe fittings having various microdamage levels

    SciTech Connect

    Mints, I.I.; Googe, S.Yu.; Shul`gina, N.G.

    1995-05-01

    Cracking resistance and metal damage are considered in relation to structural state for steam-pipe fittings during use. An approximate scheme is given for estimating the maximum permissible operating time in the plastic state in relation to the depth of an observed crack-type defect.

  20. Intermediate Levels of Resistance to Tracheal Mites in Crosses Between Resistant and Susceptible Strains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bioassays and sampling of field colonies were used to test the hypothesis that the resistance to tracheal mites in Russian honey bees is a dominant trait. Earlier studies with Buckfast bees as a resistant parent had suggested dominance or partial dominance in their crosses with either a Canadian su...

  1. Comparative genome analysis of high-level penicillin resistance in Streptococcus pneumoniae.

    PubMed

    Tait-Kamradt, Amelia G; Cronan, Melissa; Dougherty, Thomas J

    2009-06-01

    Streptococcus pneumoniae strains with very high levels of penicillin resistance (minimum inhibitory concentration [MIC] >or=8 microg/ml) emerged in the 1990 s. Previous studies have traced the changes in penicillin binding proteins (PBP) that result in decreased penicillin susceptibility, and the role of several PBP genes in high-level resistance. In the present study, we investigated the changes that occurred at the two highest levels of penicillin resistance using NimbleGen's Comparative Genome Sequencing (CGS) technology. DNA from a highly resistant (Pen MIC 16 microg/ml) pneumococcus was used to serially transform the R6 strain to high-level resistance. Four distinct levels of penicillin resistance above the susceptible R6 strain (MIC 0.016 microg/ml) were identified. Using CGS technology, the entire genome sequences of the two highest levels of resistant transformants were examined for changes associated with the resistance phenotypes. At the third level of resistance, changes in PBPs 1a, 2b, and 2x were found, very similar to previous reports. At the fourth resistance level, two additional changes were observed in the R6 transformants. More changes were observed in PBP2x, as well as in peptidoglycan GlcNAc deacetylase (pdgA), which had a missense mutation in the coding region. Genetic transformation with polymerase chain reaction (PCR) products generated from the high-level resistant parent containing either the additional PBP2x or mutant pdgA gene did not increase the MIC of the third-level transformant. Only when both PCR products were simultaneously transformed into the third-level transformant did colonies emerge that were at the highest level of resistance (16-32 microg/ml), equivalent to the highly resistant parent strain. This is the first instance of the involvement of a variant pdgA gene in penicillin resistance. It is also clear from these experiments and the literature that there are multiple paths to the pneumococcus achieving high-level

  2. Serum leptin levels in gastric cancer patients and the relationship with insulin resistance

    PubMed Central

    Aslan, Mehmet; Dulger, Ahmet Cumhur; Emre, Habib; Kemik, Ahu; Kemik, Ozgur; Esen, Ramazan

    2015-01-01

    Introduction Serum leptin levels have been examined in various cancers, with conflicting results. However, there is limited information regarding serum leptin levels and insulin resistance in gastric cancer patients. Therefore, we aimed to investigate serum leptin levels, performance status, insulin levels and insulin resistance in patients with gastric cancer. In addition, we examined the relationship between these measurements and leptin levels. Material and methods Thirty-nine patients with gastric cancer and 30 control subjects were enrolled in the study. Serum leptin, total protein, albumin, growth hormone, insulin and glucose levels were measured. The homeostasis model assessment (HOMA) was used to assess insulin resistance. Results Serum levels of insulin, glucose and growth hormone and insulin resistance were significantly lower in gastric cancer patients than controls (p < 0.05 for all). In the Pearson correlation analysis, insulin resistance was found to be significantly correlated with serum leptin levels in gastric cancer patients (r = 0.320, p = 0.047). We observed a significant negative correlation between performance status and insulin resistance in patients with cachexia (r = –0.512, p = 0.030), while no association was found in non-cachectic patients. Conclusions We concluded that serum leptin levels are significantly lower in gastric cancer patients. In addition, gastric cancer patients have decreases in insulin levels, insulin resistance and growth hormone levels. This study found a positive association between serum leptin levels and insulin resistance. Moreover, there is a negative association between serum leptin levels and growth hormone levels. Thus, low insulin and growth hormone levels may suppress the production of leptin in gastric cancer patients. PMID:25995751

  3. Development of high-level streptomycin resistance affected by a plasmid in lactic streptococci.

    PubMed

    Sinha, R P

    1986-08-01

    Some lactose-negative (Lac-) mutants of Streptococcus lactis C2 and ML3 exhibited development of very high level streptomycin resistance after incubation with subinhibitory concentrations of the drug for 18 to 22 h. These drug-resistant mutants showed no loss of resistance even after 6 months of subculturing in broth without any drug. The parental Lac+ strains did not show mutation to high-level streptomycin resistance. The Lac+ characteristic of the parental strain was conjugally transferred to Lac- derivatives of C2 and ML3, showing the ability to mutate to high-level resistance. When transconjugants were analyzed for this characteristic, they showed both mutable and nonmutable Lac+ types. The results suggested that genetic information for mutation to high-level streptomycin resistance in lactic streptococci resides on the chromosome, and its expression is affected by a plasmid. The plasmid profiles of strains C2, ML3, C2 Lac-, ML3 Lac-, and two kinds of transconjugants confirmed the presence of a plasmid of approximately 5.5 megadaltons in strains showing no mutation to high-level streptomycin resistance, while strains missing such a plasmid exhibited high-level streptomycin resistance after incubation with subinhibitory concentrations of the drug.

  4. The application of taylor weighting, digital phase shifters, and digital attenuators to phased-array antennas.

    SciTech Connect

    Brock, Billy C.

    2008-03-01

    Application of Taylor weighting (taper) to an antenna aperture can achieve low peak sidelobes, but combining the Taylor weighting with quantized attenuators and phase shifters at each radiating element will impact the performance of a phased-array antenna. An examination of array performance is undertaken from the simple point of view of the characteristics of the array factor. Design rules and guidelines for determining the Taylor-weighting parameters, the number of bits required for the digital phase shifter, and the dynamic range and number of bits required for the digital attenuator are developed. For a radar application, when each element is fed directly from a transmit/receive module, the total power radiated by the array will be reduced as a result of the taper. Consequently, the issue of whether to apply the taper on both transmit and receive configurations, or only on the receive configuration is examined with respect to two-way sidelobe performance.

  5. A tunable and wideband microwave photonic phase shifter based on dual-polarization modulator

    NASA Astrophysics Data System (ADS)

    Peng, Zhengxue; Wen, Aijun; Gao, Yongsheng; Tu, Zhaoyang

    2017-01-01

    A microwave photonic phase shifter based on dual-polarization Mach-Zehnder modulator (DPol-MZM) is proposed and experimentally demonstrated in this paper. A polarization multiplexed double sideband (DSB) signal is produced by a DPol-MZM. An optical bandpass filter (OBPF) follows after the DPol-MZM to filter out the optical carrier and one sideband. The polarization multiplexed signal is converted into a linear polarization light by a polarizer (Pol), and then beat at a photodiode (PD) to obtain the phase shifted signal. Experiments are carried out, and a continuous phase shift from -180° to 180° over a wide microwave frequency range of 10-33 GHz can be achieved by changing the polarization state using a polarization controller (PC). We also studied the spurious free dynamic range (SFDR) in the experiments. The features of this proposed phase shifter are large operation bandwidth, full-range 360° phase shift, and simple structure.

  6. Optimizing UV-glass multi-anode PMTs with a p-Terphenyl wavelength shifter

    NASA Astrophysics Data System (ADS)

    Rehfuss, Melanie; Joosten, Sylvester; Meziani, Zein-Eddine

    2015-04-01

    Due to their small form-factor, lower sensitivity to magnetic fields and potential for advanced noise-rejection, multi-anode (MA) PMTs are supremely suited for application in future open-environment Cherenkov detectors at very high luminosities. This will become critical at Jefferson Lab after the 12 GeV upgrade, as well as for a future electron-ion collider. I will present the results from performance characterization and magnetic field sensitivity testing of the 64-channel Hamamatsu H8500C-03 series MA PMT conducted at Temple University. Moreover, I will explore their behavior after the application of a p-Terphenyl wavelength shifter. Such a wavelength shifter can dramatically boost the quantum efficiency below 300 nm, strongly improving the overall Cherenkov detector efficiency.

  7. Enterococci from Bangkok, Thailand, with high-level resistance to currently available aminoglycosides.

    PubMed Central

    Murray, B E; Tsao, J; Panida, J

    1983-01-01

    Enterococcal endocarditis is usually treated with a combination of a penicillin and an aminoglycoside. Recent reports have documented the emergence of enterococci in France with high-level resistance to gentamicin, tobramycin, and kanamycin and the emergence of strains in Houston, Tex. with high-level resistance to all of these drugs and streptomycin. In this study, we examined strains from a geographic area where newer aminoglycosides have been less commonly used. Of 125 distinct patient isolates, 18 (14%) were resistant to greater than 2,000 micrograms of gentamicin and most other aminoglycosides per ml. Four of these strains transferred gentamicin resistance to a laboratory recipient. One strain, chosen for further study, was resistant to synergism between penicillin and gentamicin, tobramycin, kanamycin, streptomycin, and amikacin and demonstrated the following enzymatic activities: 3'- and 2"-aminoglycoside phosphotransferases, 6'-aminoglycoside acetyltransferase, and adenylylation of streptomycin. Optimal therapy for endocarditis caused by such highly resistant strains is currently unknown. PMID:6614889

  8. Evaluation of body weight, insulin resistance, leptin and adiponectin levels in premenopausal women with hyperprolactinemia.

    PubMed

    Atmaca, Aysegul; Bilgici, Birsen; Ecemis, Gulcin Cengiz; Tuncel, Ozgur Korhan

    2013-12-01

    The effects of hyperprolactinemia on metabolic parameters are not clear and a few data evaluating adiponectin levels in prolactinoma and idiopathic hyperprolactinemia exist. The aim of this study was to evaluate the effects of hyperprolactinemia on body weight, insulin resistance, beta cell function, and leptin and adiponectin levels in premenopausal women with hyperprolactinemia. Forty premenopausal women with prolactinoma or idiopathic hyperprolactinemia were compared to 41 age-matched healthy premenopausal women with regard to body weight, body mass index, waist and hip circumferences, waist to hip ratio, fasting plasma glucose, insulin levels, insulin resistance measured by homeostasis model assessment (HOMA)-insulin resistance index, beta cell function measured by HOMA-β index, leptin and adiponectin levels. Plasma insulin levels and HOMA indexes (both insulin resistance and beta indexes) were significantly higher in hyperprolactinemic women. The other parameters were similar between both groups. There was a positive correlation between prolactin levels and fasting plasma glucose in hyperprolactinemic women. The results of this study showed that high prolactin levels may be associated with hyperinsulinemia and insulin resistance in premenopausal women. This effect seems to be independent of body weight, leptin and adiponectin levels. High prolactin levels may directly stimulate insulin secretion from pancreas and directly cause hepatic and whole-body insulin resistance.

  9. Monolithic mm-wave phase shifter using optically activated superconducting switches

    NASA Technical Reports Server (NTRS)

    Romanofsky, Robert R. (Inventor); Bhasin, Kul B. (Inventor)

    1992-01-01

    A phase shifter is disclosed having a reference path and a delay path, light sources, and superconductive switches. Each of the superconductive switches is terminated in a virtual short circuit, which may be a radial stub. Switching between the reference path and delayed path is accomplished by illuminating the superconductive switches connected to the desired path, while not illuminating the superconductive switches connected to the other path.

  10. Multiple Mechanisms Increase Levels of Resistance in Rapistrum rugosum to ALS Herbicides

    PubMed Central

    Hatami, Zahra M.; Gherekhloo, Javid; Rojano-Delgado, Antonia M.; Osuna, Maria D.; Alcántara, Ricardo; Fernández, Pablo; Sadeghipour, Hamid R.; De Prado, Rafael

    2016-01-01

    Rapistrum rugosum (turnip weed) is a common weed of wheat fields in Iran, which is most often controlled by tribenuron-methyl (TM), a sulfonylurea (SU) belonging to the acetolactate synthase (ALS) inhibiting herbicides group. Several cases of unexplained control failure of R. rugosum by TM have been seen, especially in Golestan province-Iran. Hence, there is lack of research in evaluation of the level of resistance of the R. rugosum populations to TM, using whole plant dose-response and enzyme assays, then investigating some potential resistance mechanisms Results revealed that the resistance factor (RF) for resistant (R) populations was 2.5–6.6 fold higher than susceptible (S) plant. Neither foliar retention, nor 14C-TM absorption and translocation were the mechanisms responsible for resistance in turnip weed. Metabolism of TM was the second resistant mechanism in two populations (Ag-R5 and G-1), in which three metabolites were found. The concentration of TM for 50% inhibition of ALS enzyme activity in vitro showed a high level of resistance to the herbicide (RFs were from 28 to 38) and cross-resistance to sulfonyl-aminocarbonyl-triazolinone (SCT), pyrimidinyl-thiobenzoate (PTB) and triazolopyrimidine (TP), with no cross-resistance to imidazolinone (IMI). Substitution Pro 197 to Ser 197 provided resistance to four of five ALS-inhibiting herbicides including SU, TP, PTB, and SCT with no resistance to IMI. These results documented the first case of R. rugosum resistant population worldwide and demonstrated that both RST and NRST mechanisms are involved to the resistance level to TM. PMID:26941749

  11. Ferrite phase shifters using stress insensitive materials. Final report, July 1991-July 1993

    SciTech Connect

    Vaughn, T.; Cox, P.; Harrison, G.; Rodrigue, P.

    1993-10-01

    This RD program sponsored by the Naval Research Laboratory and being conducted by EMS Technologies, Inc., Norcross, Georgia, is focused toward achieving improved performance in microwave switching components via use of stress insensitive' microwave ferrite materials for applications where stable hysteresis characteristics of the materials are critical to the RF performance. The program, therefore, primarily addresses how to relieve or improve the magnetostrictive characteristics of the materials with emphasis on the specific application and demonstration of these materials in microwave switching components, particularly ferrite toroidal phase shifters. Material investigations were focused on Mn+3 substitutions in Yttrium-gadolinium iron garnet. These compounds were evaluated in dual toroid waveguide phase shifter structures with temperature, pressure Rf power as variables Manganese substitution per formula unit for Fe+3 of 0.11 to 0.13 (2.2 to 2.6%) produced compounds which exhibited stable performance from magnetostrictive stresses in phaser structures. Ferrite phase shifters, Stress insensitive materials Manganese substitution in garnets, Magnetostrictive, Stresses in ferrite phasers.

  12. Interplay Between Thin Film Ferroelectric Composition, Microstructure and Microwave Phase Shifter Performance

    NASA Technical Reports Server (NTRS)

    Mueller, Carl H.; VanKeuls, Frederick W.; Romanofsky, Robert R.; Alterovitz, Samuel A.; Miranda, Felix A.

    2003-01-01

    One of the keys to successfully incorporating ferroelectric films into Ku-band (12 to 18 GHz) phase shifters is to establish the composition, microstructure, and thickness required to meet the tuning needs, and tailor the film properties to meet these needs. Optimal performance is obtained when the film composition and device design are such that the device performance is limited by odd mode dielectric losses, and these losses are minimized as much as possible while still maintaining adequate tunability. The parameters required to maintain device performance will vary slightly depending on composition, but we can conclude that the best tuning-to-loss figures of merit (K-factor) are obtained when there is minimal variation between the in-plane and out-of-plane lattice parameters, and the full-width half maximum values of the BSTO (002) peaks are less than approximately 0.04 deg. We have observed that for phase shifters in which the ferroelectric crystalline quality and thickness are almost identical, higher losses are observed in films with higher BaISr ratios. The best performance was observed in phase shifters with Ba:Sr = 30:70. The superiority of this composition was attributed to several interacting factors: the B a: Sr ratio was such that the Curie temperature (180 K) was far removed from room temperature, the crystalline quality of the film was excellent, and there was virtually no difference between the inplane and out-of-plane lattice parameters of the film.

  13. Use of Lot Quality Assurance Sampling to Ascertain Levels of Drug Resistant Tuberculosis in Western Kenya

    PubMed Central

    Cohen, Ted; Zignol, Matteo; Nyakan, Edwin; Hedt-Gauthier, Bethany L.; Gardner, Adrian; Kamle, Lydia; Injera, Wilfred; Carter, E. Jane

    2016-01-01

    Objective To classify the prevalence of multi-drug resistant tuberculosis (MDR-TB) in two different geographic settings in western Kenya using the Lot Quality Assurance Sampling (LQAS) methodology. Design The prevalence of drug resistance was classified among treatment-naïve smear positive TB patients in two settings, one rural and one urban. These regions were classified as having high or low prevalence of MDR-TB according to a static, two-way LQAS sampling plan selected to classify high resistance regions at greater than 5% resistance and low resistance regions at less than 1% resistance. Results This study classified both the urban and rural settings as having low levels of TB drug resistance. Out of the 105 patients screened in each setting, two patients were diagnosed with MDR-TB in the urban setting and one patient was diagnosed with MDR-TB in the rural setting. An additional 27 patients were diagnosed with a variety of mono- and poly- resistant strains. Conclusion Further drug resistance surveillance using LQAS may help identify the levels and geographical distribution of drug resistance in Kenya and may have applications in other countries in the African Region facing similar resource constraints. PMID:27167381

  14. High Levels of Transmitted HIV Drug Resistance in a Study in Papua New Guinea

    PubMed Central

    Lavu, Evelyn; Kave, Ellan; Mosoro, Euodia; Markby, Jessica; Aleksic, Eman; Gare, Janet; Elsum, Imogen A.; Nano, Gideon; Kaima, Petronia; Dala, Nick; Gurung, Anup; Bertagnolio, Silvia; Crowe, Suzanne M.; Myatt, Mark

    2017-01-01

    Introduction Papua New Guinea is a Pacific Island nation of 7.3 million people with an estimated HIV prevalence of 0.8%. ART initiation and monitoring are guided by clinical staging and CD4 cell counts, when available. Little is known about levels of transmitted HIV drug resistance in recently infected individuals in Papua New Guinea. Methods Surveillance of transmitted HIV drug resistance in a total of 123 individuals recently infected with HIV and aged less than 30 years was implemented in Port Moresby (n = 62) and Mount Hagen (n = 61) during the period May 2013-April 2014. HIV drug resistance testing was performed using dried blood spots. Transmitted HIV drug resistance was defined by the presence of one or more drug resistance mutations as defined by the World Health Organization surveillance drug resistance mutations list. Results The prevalence of non-nucleoside reverse transcriptase inhibitor transmitted HIV drug resistance was 16.1% (95% CI 8.8%-27.4%) and 8.2% (95% CI 3.2%-18.2%) in Port Moresby and Mount Hagen, respectively. The prevalence of nucleoside reverse transcriptase inhibitor transmitted HIV drug resistance was 3.2% (95% CI 0.2%-11.7%) and 3.3% (95% CI 0.2%-11.8%) in Port Moresby and Mount Hagen, respectively. No protease inhibitor transmitted HIV drug resistance was observed. Conclusions The level of non-nucleoside reverse transcriptase inhibitor drug resistance in antiretroviral drug naïve individuals recently infected with HIV in Port Moresby is amongst the highest reported globally. This alarming level of transmitted HIV drug resistance in a young sexually active population threatens to limit the on-going effective use of NNRTIs as a component of first-line ART in Papua New Guinea. To support the choice of nationally recommended first-line antiretroviral therapy, representative surveillance of HIV drug resistance among antiretroviral therapy initiators in Papua New Guinea should be urgently implemented. PMID:28146591

  15. Genotypic and phenotypic characterization of methicillin-resistant Staphylococcus aureus (MRSA) clones with high-level mupirocin resistance.

    PubMed

    González-Domínguez, María; Seral, Cristina; Potel, Carmen; Sáenz, Yolanda; Álvarez, Maximiliano; Torres, Carmen; Castillo, Francisco Javier

    2016-06-01

    A high proportion of methicillin-resistant Staphylococcus aureus isolates recovered in one year period showed high-level mupirocin-resistance (HLMUPR-MRSA) in our environment (27.2%). HLMUPR-MRSA isolates were mainly collected from skin and soft tissue samples, and diabetes was the main related comorbidity condition. These isolates were more frequently found in vascular surgery. HLMUPR-MRSA was more resistant to aminoglycosides than mupirocin-susceptible MRSA, linked to the presence of bifunctional and/or nucleotidyltransferase enzymes with/without macrolide resistance associated with the msr(A) gene. Most of HLMUPR-MRSA isolates belonged to ST125/t067. Nine IS257-ileS2 amplification patterns (p3 was the most frequent) were observed in HLMUPR-MRSA isolates, suggesting the presence of several mupirocin-resistance-carrying plasmids in our environment and promoting the emergence of mupirocin resistance. The presence of the same IS257-ileS2 amplification pattern p3 in 65% of HLMUPR-MRSA, all of them ST125/t067, suggests a clonal spread in our hospital and community environment which could explain the high prevalence of HLMUPR-MRSA during the study period. An outbreak situation or an increase in mupirocin consumption was not observed.

  16. OCCURRENCE OF HIGH-LEVEL AMINOGLYCOSIDE RESISTANCE IN ENVIRONMENTAL ISOLATES OF ENTEROCOCCI

    EPA Science Inventory

    High-level resistance fo aminoglycosides was observed in environmental isolates of enterococci. Various aquatic habitats, including agricultural runoff, creeks, rivers, wastewater, and wells, were analyzed. Strains of Enterococcus faecalis, e.faecium, E. gallinarum, and other Ent...

  17. Graphene with different oxygenated levels in transparent resistive switching memory applications

    NASA Astrophysics Data System (ADS)

    Lin, Chun-Chieh; Tsai, Shuo-Wen; Zeng, Zih-Lun

    2017-04-01

    Graphene oxide (GO) is a two-dimensional material with a high light transmittance. The conductivity of GO can be altered by applying an electrical signal, which can be used in nonvolatile resistive switching memories. In this work, the effects of the GO oxygenated level on resistive switching properties are studied. The GO-based device with a higher oxygenated level exhibits better resistive switching properties. The transmittance of the GO-based device is demonstrated. A possible resistive switching model and band diagrams of the GO-based device are also proposed. The reported GO-based resistive switching memory device can possibly be used in new-generation nonvolatile memory and transparent devices.

  18. Broadband photonic microwave phase shifter based on controlling two RF modulation sidebands via a Fourier-domain optical processor.

    PubMed

    Yang, J; Chan, E H W; Wang, X; Feng, X; Guan, B

    2015-05-04

    An all-optical photonic microwave phase shifter that can realize a continuous 360° phase shift over a wide frequency range is presented. It is based on the new concept of controlling the amplitude and phase of the two RF modulation sidebands via a Fourier-domain optical processor. The operating frequency range of the phase shifter is largely increased compared to the previously reported Fourier-domain optical processor based phase shifter that uses only one RF modulation sideband. This is due to the extension of the lower RF operating frequency by designing the amplitude and phase of one of the RF modulation sidebands while the other sideband is designed to realize the required RF signal phase shift. The two-sideband amplitude-and-phase-control based photonic microwave phase shifter has a simple structure as it only requires a single laser source, a phase modulator, a Fourier-domain optical processor and a single photodetector. Investigation on the bandwidth limitation problem in the conventional Fourier-domain optical processor based phase shifter is presented. Comparisons between the measured phase shifter output RF amplitude and phase responses with theory, which show excellent agreement, are also presented for the first time. Experimental results demonstrate the full -180° to + 180° phase shift with little RF signal amplitude variation of less than 3 dB and with a phase deviation of less than 4° over a 7.5 GHz to 26.5 GHz frequency range, and the phase shifter exhibits a long term stable performance.

  19. High-level gentamicin resistance and vancomycin resistance in clinical isolates of enterococci in a tertiary care hospital in eastern Nepal.

    PubMed

    Nepal, H P; Khanal, B; Acharya, A; Gyawali, N; Jha, P K; Paudel, R

    2012-03-01

    High-level gentamicin resistance and vancomycin resistance in enterococci, a family of important opportunistic pathogens, have emerged as a significant clinical problem over recent years. The present study was conducted to determine the high-level gentamicin and vancomycin resistance among the clinical isolates of enterococci. A total of 110 phenotypically identified enterococcal isolates were subjected to determination of high-level gentamicin resistance (by disk diffusion and agar dilution methods) and vancomycin resistance (by agar screening and agar dilution methods). About 36% of the isolates were found to have high-level gentamicin resistance, which indicates that gentamicin no longer remains an appropriate choice for inclusion in combination therapy with cell wall-active agents. Ten percent isolates exhibited resisance to vancomycin during screening. However, agar dilution confirmed that the isolates did not have resistance to vancomycin but had reduced susceptibility to it, which indicates their impending emergence of resistance to vancomycin.

  20. A high level of transgenic viral small RNA is associated with broad potyvirus resistance in cucurbits.

    PubMed

    Leibman, Diana; Wolf, Dalia; Saharan, Vinod; Zelcer, Aaron; Arazi, Tzahi; Yoel, Shiboleth; Gaba, Victor; Gal-On, Amit

    2011-10-01

    Gene-silencing has been used to develop resistance against many plant viruses but little is known about the transgenic small-interfering RNA (t-siRNA) that confers this resistance. Transgenic cucumber and melon lines harboring a hairpin construct of the Zucchini yellow mosaic potyvirus (ZYMV) HC-Pro gene accumulated different levels of t-siRNA (6 to 44% of total siRNA) and exhibited resistance to systemic ZYMV infection. Resistance to Watermelon mosaic potyvirus and Papaya ring spot potyvirus-W was also observed in a cucumber line that accumulated high levels of t-siRNA (44% of total siRNA) and displayed significantly increased levels of RNA-dependent RNA (RDR)1 and Argonaute 1, as compared with the other transgenic and nontransformed plants. The majority of the t-siRNA sequences were 21 to 22 nucleotides in length and sense strand biased. The t-siRNA were not uniformly distributed throughout the transgene but concentrated in "hot spots" in a pattern resembling that of the viral siRNA peaks observed in ZYMV-infected cucumber and melon. Mutations in ZYMV at the loci associated with the siRNA peaks did not break this resistance, indicating that hot spot t-siRNA may not be essential for resistance. This study shows that resistance based on gene-silencing can be effective against related viruses and is probably correlated with t-siRNA accumulation and increased expression of RDR1.

  1. [Vancomycin and high-level aminoglycoside resistant Enterococcus carriage and the risk factors related to resistance in hospitalized patients].

    PubMed

    Yildirim, Mustafa; Sencan, Irfan; Ozdemir, Davut; Oksüz, Sükrü; Yilmaz, Zeynep; Sahin, Idris

    2007-04-01

    The aims of this study were to detect the prevalence of fecal vancomycin resistant Enterococcus (VRE) colonization with high-level resistance to aminoglycoside and other antibiotics and, the risk factors related to resistance in hospitalized patients in Düzce Medical Faculty Hospital, Turkey. A total of 105 patients (61 from internal medicine, 44 from surgery clinics; 54.3% female, mean age: 47.2 +/- 24.54 years) were included to the study and a single stool sample was collected from each of the patients. Specimens were cultivated in Enterococcus selective media (BioMerieux, France), and the isolates were identified by conventional microbiological methods together with the API 20 Strep test. Beta-lactamase activities of the isolates were tested with nitrocefin disk, and antibiotic susceptibilities were determined by the disk diffusion method. Enterococcus spp. were isolated from 81 (77%) of the patients' samples and 60.5% were identified as E. faecium, 13.6% as E. faecalis, 11.1% as E. gallinarum, 7.4% as E. durans, 2.5% as E. raffinosus, 2.5% as E. mundtii, 1.2% as E. casseliflavus, and 1.2% as E. avium. High-level streptomycin and gentamicin resistance rates were found in 19.8% and 9.9% of the isolates, respectively. The resistance rates for the other antibiotics were found as follows; 18.5% to ampicillin, 27.2% to penicilin, 34.6% to nitrofurantoin, 65.4% to norfloxacin, and 70.4% to both tetracycline and ciprofloxacin. No vancomycin resistance was detected, and none of the enterococci had beta-lactamase activity. Long hospitalization period, antibiotic usage and experience of intra-abdominal operation were found as the significant risk factors for colonization of the resistant bacteria. Our results demonstrated that there was no fecal VRE carriage in our hospital during the study period, however, it was concluded that the screening tests should be done periodically in order to detect resistant strains as soon as possible.

  2. Millimeter-wave diode-grid phase shifters

    NASA Technical Reports Server (NTRS)

    Lam, Wayne W.; Stolt, Kjell S.; Jou, Christina F.; Luhmann, Neville C., Jr.; Chen, Howard Z.

    1988-01-01

    Monolithic diode grids have been fabricated on 2-cm square gallium-arsenide wafers with 1600 Schottky-barrier varactor diodes. Shorted diodes are detected with a liquid-crystal technique, and the bad diodes are removed with an ultrasonic probe. A small-aperture reflectometer that uses wavefront division interference was developed to measure the reflection coefficient of the grids. A phase shift of 70 deg with a 7-dB loss was obtained at 93 GHz when the bias on the diode grid was changed from -3 V to 1 V. A simple transmission-line grid model, together with the measured low-frequency parameters for the diodes, was shown to predict the measured performance over the entire capacitive bias range of the diodes, as well as over the complete reactive tuning range provided by a reflector behind the grid, and over a wide range of frequencies from 33 GHz to 141 GHz. This shows that the transmission-line model and the measured low-frequency diode parameters can be used to design an electronic beam-steering array and to predict its performance. An electronic beam-steering array made of a pair of grids using state-of-the-art diodes with 5-ohm series resistances would have a loss of 1.4 dB at 90 GHz.

  3. EPSPS Gene Copy Number and Whole-Plant Glyphosate Resistance Level in Kochia scoparia.

    PubMed

    Gaines, Todd A; Barker, Abigail L; Patterson, Eric L; Westra, Philip; Westra, Eric P; Wilson, Robert G; Jha, Prashant; Kumar, Vipan; Kniss, Andrew R

    2016-01-01

    Glyphosate-resistant (GR) Kochia scoparia has evolved in dryland chemical fallow systems throughout North America and the mechanism of resistance involves 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene duplication. Agricultural fields in four states were surveyed for K. scoparia in 2013 and tested for glyphosate-resistance level and EPSPS gene copy number. Glyphosate resistance was confirmed in K. scoparia populations collected from sugarbeet fields in Colorado, Wyoming, and Nebraska, and Montana. Glyphosate resistance was also confirmed in K. scoparia accessions collected from wheat-fallow fields in Montana. All GR samples had increased EPSPS gene copy number, with median population values up to 11 from sugarbeet fields and up to 13 in Montana wheat-fallow fields. The results indicate that glyphosate susceptibility can be accurately diagnosed using EPSPS gene copy number.

  4. EPSPS Gene Copy Number and Whole-Plant Glyphosate Resistance Level in Kochia scoparia

    PubMed Central

    Gaines, Todd A.; Barker, Abigail L.; Patterson, Eric L.; Westra, Philip; Westra, Eric P.; Wilson, Robert G.; Jha, Prashant; Kumar, Vipan

    2016-01-01

    Glyphosate-resistant (GR) Kochia scoparia has evolved in dryland chemical fallow systems throughout North America and the mechanism of resistance involves 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene duplication. Agricultural fields in four states were surveyed for K. scoparia in 2013 and tested for glyphosate-resistance level and EPSPS gene copy number. Glyphosate resistance was confirmed in K. scoparia populations collected from sugarbeet fields in Colorado, Wyoming, and Nebraska, and Montana. Glyphosate resistance was also confirmed in K. scoparia accessions collected from wheat-fallow fields in Montana. All GR samples had increased EPSPS gene copy number, with median population values up to 11 from sugarbeet fields and up to 13 in Montana wheat-fallow fields. The results indicate that glyphosate susceptibility can be accurately diagnosed using EPSPS gene copy number. PMID:27992501

  5. High Levels of Resistance in the Common Bed Bug, Cimex lectularius (Hemiptera: Cimicidae), to Neonicotinoid Insecticides.

    PubMed

    Romero, Alvaro; Anderson, Troy D

    2016-05-01

    The rapid increase of bed bug populations resistant to pyrethroids demands the development of novel control tactics. Products combining pyrethroids and neonicotinoids have become very popular for bed bug control in the United States, but there are concerns about evolution of resistance to these compounds. Laboratory assays were used to measure the toxicity of topical applications of four neonicotinoids to a susceptible population and three pyrethroid-resistant populations. Activity of esterases, glutathione S-transferases, and cytochrome P450s of all strains was also evaluated. High levels of resistance to four neonicotinoids, acetamiprid, imidacloprid, dinotefuran, and thiamethoxam, relative to the susceptible Fort Dix population, were detected in populations collected from human dwellings in Cincinnati and Michigan. Because activity of detoxifying enzymes was increased in these two populations, our results suggest that these enzymes have some involvement in neonicotinoid resistance, but other resistance mechanisms might be involved as well. Detection of high levels of resistance to neonicotinoids further limits the options for chemical control of bed bugs.

  6. Molecular Characterization of High-Level Mupirocin Resistance in Staphylococcus pseudintermedius

    PubMed Central

    Pérez-Roth, Eduardo; Pintarić, Selma; Šeol Martinec, Branka

    2013-01-01

    The genetic analysis of high-level mupirocin resistance (Hi-Mupr) in a Staphylococcus pseudintermedius isolate from a dog is presented. The Hi-Mupr ileS2 gene flanked by a novel rearrangement of directly repeated insertion sequence IS257 elements was located, together with the aminoglycoside resistance aacA-aphD determinant, on a conjugative plasmid related to the pSK41/pGO1 family plasmids. PMID:23269741

  7. Effects of Mn2+ Levels on the Resistance Properties of Bacillus cereus Spores

    DTIC Science & Technology

    2013-01-01

    properties of Bacillus megaterium spores, with elevated Mn levels associated with increased spore resistance to wet or dry heat, UVC radiation, and...RA (1974). The formation of Bacillus megaterium spores having increased heat and radiation resistance and variable heat shock requirements due to... Bacillus megaterium by wet heat. Lett. Appl. Microbiol. 50:507-514. Daly MJ (2012) Death by protein damage in irradiated cells. DNA Repair 11:12-21

  8. High level resistance against rhizomania disease by simultaneously integrating two distinct defense mechanisms.

    PubMed

    Pavli, Ourania I; Tampakaki, Anastasia P; Skaracis, George N

    2012-01-01

    With the aim of achieving durable resistance against rhizomania disease of sugar beet, the employment of different sources of resistance to Beet necrotic yellow vein virus was pursued. To this purpose, Nicotiana benthamiana transgenic plants that simultaneously produce dsRNA originating from a conserved region of the BNYVV replicase gene and the HrpZ(Psph) protein in a secreted form (SP/HrpZ(Psph)) were produced. The integration and expression of both transgenes as well as proper production of the harpin protein were verified in all primary transformants and selfed progeny (T1, T2). Transgenic resistance was assessed by BNYVV-challenge inoculation on T2 progeny by scoring disease symptoms and DAS-ELISA at 20 and 30 dpi. Transgenic lines possessing single transformation events for both transgenes as well as wild type plants were included in inoculation experiments. Transgenic plants were highly resistant to virus infection, whereas in some cases immunity was achieved. In all cases, the resistant phenotype of transgenic plants carrying both transgenes was superior in comparison with the ones carrying a single transgene. Collectively, our findings demonstrate, for a first time, that the combination of two entirely different resistance mechanisms provide high level resistance or even immunity against the virus. Such a novel approach is anticipated to prevent a rapid virus adaptation that could potentially lead to the emergence of isolates with resistance breaking properties.

  9. Gyrase Mutations Are Associated with Variable Levels of Fluoroquinolone Resistance in Mycobacterium tuberculosis

    PubMed Central

    Jacobson, Karen R.; Franke, Molly F.; Kaur, Devinder; Sloutsky, Alex; Mitnick, Carole D.; Murray, Megan

    2016-01-01

    Molecular diagnostics that rapidly and accurately predict resistance to fluoroquinolone drugs and especially later-generation agents promise to improve treatment outcomes for patients with multidrug-resistant tuberculosis and prevent the spread of disease. Mutations in the gyr genes are known to confer most fluoroquinolone resistance, but knowledge about the effects of gyr mutations on susceptibility to early- versus later-generation fluoroquinolones and about the role of mutation-mutation interactions is limited. Here, we sequenced the full gyrA and gyrB open reading frames in 240 multidrug-resistant and extensively drug-resistant tuberculosis strains and quantified their ofloxacin and moxifloxacin MIC by testing growth at six concentrations for each drug. We constructed a multivariate regression model to assess both the individual mutation effects and interactions on the drug MICs. We found that gyrB mutations contribute to fluoroquinolone resistance both individually and through interactions with gyrA mutations. These effects were statistically significant. In these clinical isolates, several gyrA and gyrB mutations conferred different levels of resistance to ofloxacin and moxifloxacin. Consideration of gyr mutation combinations during the interpretation of molecular test results may improve the accuracy of predicting the fluoroquinolone resistance phenotype. Further, the differential effects of gyr mutations on the activity of early- and later-generation fluoroquinolones requires further investigation and could inform the selection of a fluoroquinolone for treatment. PMID:26763957

  10. Wideband 360 degrees microwave photonic phase shifter based on slow light in semiconductor optical amplifiers.

    PubMed

    Xue, Weiqi; Sales, Salvador; Capmany, José; Mørk, Jesper

    2010-03-15

    In this work we demonstrate for the first time, to the best of our knowledge, a continuously tunable 360 degrees microwave phase shifter spanning a microwave bandwidth of several tens of GHz (up to 40 GHz). The proposed device exploits the phenomenon of coherent population oscillations, enhanced by optical filtering, in combination with a regeneration stage realized by four-wave mixing effects. This combination provides scalability: three hybrid stages are demonstrated but the technology allows an all-integrated device. The microwave operation frequency limitations of the suggested technique, dictated by the underlying physics, are also analyzed.

  11. Generation of energetic, picosecond seed pulses for CO2 laser using Raman shifter

    NASA Astrophysics Data System (ADS)

    Welch, Eric; Tochitsky, Sergei; Joshi, Chan

    2017-03-01

    We present a new concept for generating 3 ps seed pulses for a high-power CO2 laser amplifier that are multiple orders more energetic than seed pulses generated by slicing from a nanosecond CO2 laser pulse. We propose to send a 1 µm picosecond laser through a C6D6 Raman shifter and mix both the pump and shifted components in a DFG crystal to produce pulses at 10.6 µm. Preliminary results of a proof-of-principle experiment are presented.

  12. Novel Phased Array Scanning Employing A Single Feed Without Using Individual Phase Shifters

    NASA Technical Reports Server (NTRS)

    Host, Nicholas K.; Chen, Chi-Chih; Volakis, John L.; Miranda, Felix A.

    2012-01-01

    Phased arrays afford many advantages over mechanically steered systems. However, they are also more complex, heavy, and most of all costly. The high cost mainly originates from the complex feeding structure. This paper proposes a novel feeding scheme to eliminate all phase shifters and achieve scanning via one-dimensional motion. Beam scanning is achieved via a series fed array incorporating feeding transmission lines whose wave velocity can be mechanically adjusted. Along with the line design, ideal element impedances to be used in conjunction with the line are derived. Practical designs are shown which achieve scanning to +/-30deg from boresight. Finally, a prototype is fabricated and measured, demonstrating the concept.

  13. Gas scintillation drift chambers with wave shifter read-out for hard X-ray astronomy

    NASA Technical Reports Server (NTRS)

    Sadoulet, Bernard; Lin, Robert P.; Weiss, Steven C.

    1987-01-01

    A major improvement in hard X-ray and gamma ray astrophysics could be provided by high pressure xenon time projection chambers where gas scintillation is used both for the measurement of the time of interaction and for the detection of the extracted electrons. This allows three dimensional imaging of naturally complex events (photoelectric interaction with escape photon, Compton scatter, and pair production). A novel read-out system based on wave shifter fibers, which is well suited to the high pressures and large areas required of a hard X-ray telescope is proposed. Expected performances are computed, potential problems are outlined, and the experimental effort to solve these problems are described.

  14. Evaluation of wavelength shifters for spectral separation of barium fluoride emissions

    SciTech Connect

    DeVol, Timothy A.

    1993-01-01

    BaF2 has the advantage over other scintillators, when comparing radiation hardness, scintillation decay time, and fast scintillation yield. Since the fast BaF2 emissions have peak wavelengths of 220, 195, and 170 nm, a wavelength shifter (WLS) is needed. Organic fluors were evaluated as WLS components. Results indicate that spectral separation using WLS is possible, but not to the extent desired; other techniques must be used also. Alternative scintillators, such as CeF3, should be investigated.

  15. Optical properties of new wide heterogeneous waveguides with thermo optical shifters.

    PubMed

    De Leonardis, Francesco; Tsarev, Andrei V; Passaro, Vittorio M

    2008-12-22

    We present analysis and simulation of novel silicon-on-insulator (SOI) heterogeneous waveguides with thermo-optic phase shifters. New structure design contains a p-n junction on both sides of SOI ridge waveguide with 220 nm x 35 microm silicon core. Strongly mode-dependent optical losses (by additional free charge absorption) provide quasi-singe-mode behavior of wide waveguide with mode size approximately 10 microm. Local heater produces an efficient phase shifting by small temperature increase (DeltaT approximately 2K), switching power (< 40 mW) and switching time (< 10 micros). Mode optical losses are significantly decreased at high heating (DeltaT approximately 120 K).

  16. Serum Fetuin-A levels, insulin resistance and oxidative stress in women with polycystic ovary syndrome.

    PubMed

    Enli, Yasar; Fenkci, Semin Melahat; Fenkci, Veysel; Oztekin, Ozer

    2013-12-01

    This study was designed to determine serum Fetuin-A levels and establish whether serum Fetuin-A level is related with insulin resistance, oxidative stress, ovarian hyperandrogenism and dyslipidemia in women with polycystic ovary syndrome (PCOS). Twenty-two patients with PCOS and twenty-one healthy control women were evaluated in this controlled clinical study. Serum Fetuin-A, lipid fractions, glucose, insulin, malondialdehyde (MDA), myeloperoxidase (MPO), glutathione (GSH), superoxide dismutase (SOD) and other hormone (gonadotropins, androgens) levels were measured. The estimate of insulin resistance was calculated by homeostasis model assessment (HOMA-R). The women with PCOS had significantly higher serum fasting glucose, insulin, luteinizing hormone (LH), MDA, Fetuin-A levels, and LH/follicle-stimulating hormone (FSH) ratio, free androgen index (FAI), HOMA-IR than healthy women. However, sex hormone-binding globulin (SHBG) and GSH levels were significantly lower in patients with PCOS compared with controls. Fetuin-A was positively correlated with insulin, HOMA-IR and FAI. Multiple regression analysis revealed that FAI was strong predictor of serum Fetuin-A level. Serum Fetuin-A level was related with insulin resistance and ovarian hyperandrogenism in women with PCOS. These results suggest that Fetuin-A may have a role in triggering the processes leading to insulin resistance and androgen excess in PCOS.

  17. Tunable Multifunctional Thermal Metamaterials: Manipulation of Local Heat Flux via Assembly of Unit-Cell Thermal Shifters

    PubMed Central

    Park, Gwanwoo; Kang, Sunggu; Lee, Howon; Choi, Wonjoon

    2017-01-01

    Thermal metamaterials, designed by transformation thermodynamics are artificial structures that can actively control heat flux at a continuum scale. However, fabrication of them is very challenging because it requires a continuous change of thermal properties in materials, for one specific function. Herein, we introduce tunable thermal metamaterials that use the assembly of unit-cell thermal shifters for a remarkable enhancement in multifunctionality as well as manufacturability. Similar to the digitization of a two-dimensional image, designed thermal metamaterials by transformation thermodynamics are disassembled as unit-cells thermal shifters in tiny areas, representing discretized heat flux lines in local spots. The programmed-reassembly of thermal shifters inspired by LEGO enable the four significant functions of thermal metamaterials—shield, concentrator, diffuser, and rotator—in both simulation and experimental verification using finite element method and fabricated structures made from copper and PDMS. This work paves the way for overcoming the structural and functional limitations of thermal metamaterials. PMID:28106156

  18. Generation of phase-coded microwave signals using a polarization-modulator-based photonic microwave phase shifter.

    PubMed

    Zhang, Yamei; Pan, Shilong

    2013-03-01

    A scheme for the generation of phase-coded microwave signals using an electrically tunable photonic microwave phase shifter is proposed and demonstrated. The photonic phase shifter is based on a single-sideband polarization modulator (PolM), and the tuning of the phase shifter is implemented by a second PolM. By introducing an RF signal to the first PolM and an electrical coding signal to the second PolM, a phase-coded microwave signal with binary phase codes or polyphase codes is achieved. An experiment is performed. The simple and flexible operation, high coding rate, large frequency range, excellent transmission performance, and high stability of the system is confirmed.

  19. Tunable Multifunctional Thermal Metamaterials: Manipulation of Local Heat Flux via Assembly of Unit-Cell Thermal Shifters

    NASA Astrophysics Data System (ADS)

    Park, Gwanwoo; Kang, Sunggu; Lee, Howon; Choi, Wonjoon

    2017-01-01

    Thermal metamaterials, designed by transformation thermodynamics are artificial structures that can actively control heat flux at a continuum scale. However, fabrication of them is very challenging because it requires a continuous change of thermal properties in materials, for one specific function. Herein, we introduce tunable thermal metamaterials that use the assembly of unit-cell thermal shifters for a remarkable enhancement in multifunctionality as well as manufacturability. Similar to the digitization of a two-dimensional image, designed thermal metamaterials by transformation thermodynamics are disassembled as unit-cells thermal shifters in tiny areas, representing discretized heat flux lines in local spots. The programmed-reassembly of thermal shifters inspired by LEGO enable the four significant functions of thermal metamaterials—shield, concentrator, diffuser, and rotator—in both simulation and experimental verification using finite element method and fabricated structures made from copper and PDMS. This work paves the way for overcoming the structural and functional limitations of thermal metamaterials.

  20. High Level Aminoglycoside Resistance and Distribution of Aminoglycoside Resistant Genes among Clinical Isolates of Enterococcus Species in Chennai, India

    PubMed Central

    Padmasini, Elango; Padmaraj, R.; Ramesh, S. Srivani

    2014-01-01

    Enterococci are nosocomial pathogen with multiple-drug resistance by intrinsic and extrinsic mechanisms. Aminoglycosides along with cell wall inhibitors are given clinically for treating enterococcal infections. 178 enterococcal isolates were analyzed in this study. E. faecalis is identified to be the predominant Enterococcus species, along with E. faecium, E. avium, E. hirae, E. durans, E. dispar and E. gallinarum. High level aminoglycoside resistance (HLAR) by MIC for gentamicin (GM), streptomycin (SM) and both (GM + SM) antibiotics was found to be 42.7%, 29.8%, and 21.9%, respectively. Detection of aminoglycoside modifying enzyme encoding genes (AME) in enterococci was identified by multiplex PCR for aac(6′)-Ie-aph(2′′)-Ia; aph(2′′)-Ib; aph(2′′)-Ic; aph(2′′)-Id and aph(3′)-IIIa genes. 38.2% isolates carried aac(6′)-Ie-aph(2′′)-Ia gene and 40.4% isolates carried aph(3′)-IIIa gene. aph(2′′)-Ib; aph(2′′)-Ic; aph(2′′)-Id were not detected among our study isolates. aac(6′)-Ie-aph(2′′)-Ia and aph(3′)-IIIa genes were also observed in HLAR E. durans, E. avium, E. hirae, and E. gallinarum isolates. This indicates that high level aminoglycoside resistance genes are widely disseminated among isolates of enterococci from Chennai. PMID:24672306

  1. Correlation of pncA sequence with pyrazinamide resistance level in BACTEC for 21 mycobacterium tuberculosis clinical isolates.

    PubMed

    Mestdagh, M; Realini, L; Fonteyne, P A; Rossau, R; Jannes, G; Mijs, W; DE Smet, K A; Portaels, F; Van den Eeckhout, E

    2000-01-01

    Mutations in the pncA gene, encoding pyrazinamidase, are considered the major mechanism of pyrazinamide (PZA) resistance in Mycobacterium tuberculosis, but resistant strains containing the wild-type gene have been described. The correlation of pncA sequence with PZA resistance level was examined for 21 M. tuberculosis clinical isolates. Susceptibility patterns were determined for 100, 300, and 900 microg/ml concentrations of the drug in BACTEC. Insertions and deletions and a substitution in the putative promoter region led to high-level resistance, whereas substitutions within the open reading frame seemed to confer variable levels of resistance. Variable resistance levels and PZase activities were also observed among isolates lacking pncA mutations. The high-level resistance (900 microg/ml) in pncA wild-type isolates highlights the clinical significance of these isolates. These data also suggest that there may still be more than one alternative mechanism leading to PZA resistance in M. tuberculosis isolates.

  2. New universal primers for genotyping and resistance detection of low HBV DNA levels.

    PubMed

    Tong, Yongqing; Liu, Bei; Liu, Hui; Zheng, Hongyun; Gu, Jian; Liu, Hang; Lin, Min; Ding, Yali; Song, Chunhua; Li, Yan

    2016-08-01

    HBV (hepatitis B virus) genotyping is important in determining the clinical manifestation of disease and treatment response, particularly, in patients with low viral loads. Also, sensitive detection of HBV antiviral drug resistance mutations is essential for monitoring therapy response.Asensitive direct sequencing method for genotyping and the drug resistance mutation detection of low levels of HBV DNA in patients' plasma is developed by PCR amplification of the DNA with novel universal primers.The novel, common, and universal primers were identified by alignment of RT region of all the HBV DNA sequences in databases. These primers could efficiently amplify the RT region of HBV virus at low DNA levels by directly sequencing the resulting PCR products, and mapping with the reference sequence made it possible to clearly obtain the HBV subtypes and identify the resistance mutations in the samples with HBV DNA level as low as 20 IU/mL. We examined the reliability of the method in clinical samples, and found it could detect the HBV subtypes and drug resistance mutations in 80 clinical HBV samples with low HBV DNA levels ranging from 20 to 200 IU/mL.This method is a sensitive and reliable direct sequencing method for HBV genotyping and antiviral drug resistance mutation detection, and is helpful for efficiently monitoring the response to therapy in HBV patients.

  3. Serum betatrophin levels are increased and associated with insulin resistance in patients with polycystic ovary syndrome.

    PubMed

    Qu, Qinglan; Zhao, Dongmei; Zhang, Fengrong; Bao, Hongchu; Yang, Qiuhua

    2017-02-01

    Objective Betatrophin is a newly identified circulating protein that is significantly associated with type 2 diabetes mellitus (T2DM), adiposity, and metabolic syndrome. The aim of this study was to investigate whether betatrophin levels and polycystic ovary syndrome (PCOS) were associated. Methods Circulating betatrophin levels were measured in 162 patients with PCOS and 156 matched control females using specific enzyme-linked immunosorbent assay kits. Correlations between betatrophin levels and PCOS incidence as well as multiple key endocrine PCOS parameters were analyzed using multiple statistical methods. Results Betatrophin levels were significantly increased in patients with PCOS (685.3 ± 27.7 vs. 772.6 ± 42.5 pg/ml). When sub-grouping all investigated subjects according to the presence of insulin resistance, women with PCOS and insulin resistance exhibited markedly higher betatrophin concentrations. Furthermore, betatrophin levels were significantly correlated with fasting insulin levels and homeostatic model assessment of insulin resistance only in females with PCOS ( r = 0.531 and r = 0.628, respectively). Conclusion We provide the first report that betatrophin is strongly associated with PCOS. This study suggests that betatrophin may potentially serve as an independent predictor for the development of PCOS in at-risk women, especially those with insulin resistance.

  4. Investigating excitation-dependent and fringe-field effects of electromagnet and permanent-magnet phase shifters for a crossed undulator

    NASA Astrophysics Data System (ADS)

    Chung, Ting-Yi; Yang, Chih-Sheng; Chu, Yun-Liang; Lin, Fu-Yuan; Jan, Jyh-Chyuan; Hwang, Ching-Shiang

    2017-04-01

    To enhance the flux density or to control polarization, a phase shifter was designed and used to modulate the phase matching between segmented undulators. A larger hysteresis loop causes, however, a repeatability issue in the phase matching; the fringe field of the phase shifter creates an extra magnetic-field error. The design of the phase shifter must therefore minimize the hysteresis loop and fringe field to maintain the phases exact and to ignore the crosstalk effect. Two critical issues are the hysteresis-loop problem and the fringe-field effect, which determine the radiation performance and the stability of the ring. To investigate these issues, a phase shifter was constructed to operate in accordance with electromagnetic- and permanent-type magnets; the results from the field measurements and shims are discussed here. The shimming algorithm and a compact permanent-magnet phase shifter that eliminates the issues are also presented.

  5. Effects of YM155 on survivin levels and viability in neuroblastoma cells with acquired drug resistance

    PubMed Central

    Voges, Yvonne; Michaelis, Martin; Rothweiler, Florian; Schaller, Torsten; Schneider, Constanze; Politt, Katharina; Mernberger, Marco; Nist, Andrea; Stiewe, Thorsten; Wass, Mark N; Rödel, Franz; Cinatl, Jindrich

    2016-01-01

    Resistance formation after initial therapy response (acquired resistance) is common in high-risk neuroblastoma patients. YM155 is a drug candidate that was introduced as a survivin suppressant. This mechanism was later challenged, and DNA damage induction and Mcl-1 depletion were suggested instead. Here we investigated the efficacy and mechanism of action of YM155 in neuroblastoma cells with acquired drug resistance. The efficacy of YM155 was determined in neuroblastoma cell lines and their sublines with acquired resistance to clinically relevant drugs. Survivin levels, Mcl-1 levels, and DNA damage formation were determined in response to YM155. RNAi-mediated depletion of survivin, Mcl-1, and p53 was performed to investigate their roles during YM155 treatment. Clinical YM155 concentrations affected the viability of drug-resistant neuroblastoma cells through survivin depletion and p53 activation. MDM2 inhibitor-induced p53 activation further enhanced YM155 activity. Loss of p53 function generally affected anti-neuroblastoma approaches targeting survivin. Upregulation of ABCB1 (causes YM155 efflux) and downregulation of SLC35F2 (causes YM155 uptake) mediated YM155-specific resistance. YM155-adapted cells displayed increased ABCB1 levels, decreased SLC35F2 levels, and a p53 mutation. YM155-adapted neuroblastoma cells were also characterized by decreased sensitivity to RNAi-mediated survivin depletion, further confirming survivin as a critical YM155 target in neuroblastoma. In conclusion, YM155 targets survivin in neuroblastoma. Furthermore, survivin is a promising therapeutic target for p53 wild-type neuroblastomas after resistance acquisition (neuroblastomas are rarely p53-mutated), potentially in combination with p53 activators. In addition, we show that the adaptation of cancer cells to molecular-targeted anticancer drugs is an effective strategy to elucidate a drug's mechanism of action. PMID:27735941

  6. Behavioral Avoidance - Will Physiological Insecticide Resistance Level of Insect Strains Affect Their Oviposition and Movement Responses?

    PubMed

    Nansen, Christian; Baissac, Olivier; Nansen, Maria; Powis, Kevin; Baker, Greg

    2016-01-01

    Agricultural organisms, such as insect herbivores, provide unique opportunities for studies of adaptive evolutionary processes, including effects of insecticides on movement and oviposition behavior. In this study, Brassica leaves were treated with one of two non-systemic insecticides and exposed to two individual strains (referred to as single or double resistance) of diamondback moth (Plutella xylostella) (DBM) exhibiting physiological resistance. Behavioral responses by these two strains were compared as part of characterizing the relative effect of levels of physiological resistance on the likelihood of insects showing signs of behavioral avoidance. For each DBM strain, we used choice bioassays to quantify two possible types of behavioral avoidance: 1) females ovipositing predominantly on leaf surfaces without insecticides, and 2) larvae avoiding insecticide-treated leaf surfaces. In three-choice bioassays (leaves with no pesticide, 50% coverage with pesticide, or 100% coverage with pesticide), females from the single resistance DBM strain laid significantly more eggs on water treated leaves compared to leaves with 100% insecticide coverage (both gamma-cyhalothrin and spinetoram). Females from the double resistance DBM strain also laid significantly more eggs on water treated leaves compared to leaves with 100% gamma-cyhalothrin, while moths did not adjust their oviposition behavior in response to spinetoram. Larvae from the single resistance DBM strain showed a significant increase in mobility in response to both insecticides and avoided insecticide-treated portions of leaves when given a choice. On the other hand, DBM larvae from the double resistance strain showed a significant decrease in mobility in response to insecticides, and they did not avoid insecticide-treated portions of leaves when given a choice. Our results suggest that pest populations with physiological resistance may show behavioral avoidance, as resistant females avoided oviposition on

  7. Behavioral Avoidance - Will Physiological Insecticide Resistance Level of Insect Strains Affect Their Oviposition and Movement Responses?

    PubMed Central

    Nansen, Christian; Baissac, Olivier; Nansen, Maria; Powis, Kevin; Baker, Greg

    2016-01-01

    Agricultural organisms, such as insect herbivores, provide unique opportunities for studies of adaptive evolutionary processes, including effects of insecticides on movement and oviposition behavior. In this study, Brassica leaves were treated with one of two non-systemic insecticides and exposed to two individual strains (referred to as single or double resistance) of diamondback moth (Plutella xylostella) (DBM) exhibiting physiological resistance. Behavioral responses by these two strains were compared as part of characterizing the relative effect of levels of physiological resistance on the likelihood of insects showing signs of behavioral avoidance. For each DBM strain, we used choice bioassays to quantify two possible types of behavioral avoidance: 1) females ovipositing predominantly on leaf surfaces without insecticides, and 2) larvae avoiding insecticide-treated leaf surfaces. In three-choice bioassays (leaves with no pesticide, 50% coverage with pesticide, or 100% coverage with pesticide), females from the single resistance DBM strain laid significantly more eggs on water treated leaves compared to leaves with 100% insecticide coverage (both gamma-cyhalothrin and spinetoram). Females from the double resistance DBM strain also laid significantly more eggs on water treated leaves compared to leaves with 100% gamma-cyhalothrin, while moths did not adjust their oviposition behavior in response to spinetoram. Larvae from the single resistance DBM strain showed a significant increase in mobility in response to both insecticides and avoided insecticide-treated portions of leaves when given a choice. On the other hand, DBM larvae from the double resistance strain showed a significant decrease in mobility in response to insecticides, and they did not avoid insecticide-treated portions of leaves when given a choice. Our results suggest that pest populations with physiological resistance may show behavioral avoidance, as resistant females avoided oviposition on

  8. Sampling considerations for herd-level measurement of faecal Escherichia coli antimicrobial resistance in finisher pigs.

    PubMed Central

    Dunlop, R. H.; McEwen, S. A.; Meek, A. H.; Friendship, R. M.; Black, W. D.; Clarke, R. C.

    1999-01-01

    The objective of this study was to determine the most efficient means of sampling faeces of finisher pigs for accurate and precise farm-level estimates of antimicrobial resistance among faecal Escherichia coli. Resistance to tetracycline and gentamicin of 8250 isolates of E. coli from 55 finisher pigs on one farm was measured with a hydrophobic grid membrane filter method. The between-pig, within-pen component of variance in resistance was large (97.5%), while between-pen, within-room and between-room components were small (2.5% and 0%, respectively). Using these resistance data, the abilities of two sampling strategies to estimate prevalence were modelled with a Monte Carlo 'bootstrap' procedure. Compositing faecal samples from several pigs before testing produced unbiased and precise estimates of prevalence and is simpler technically than individual animal testing. PMID:10459654

  9. Selection of a multidrug resistance plasmid by sublethal levels of antibiotics and heavy metals.

    PubMed

    Gullberg, Erik; Albrecht, Lisa M; Karlsson, Christoffer; Sandegren, Linus; Andersson, Dan I

    2014-10-07

    How sublethal levels of antibiotics and heavy metals select for clinically important multidrug resistance plasmids is largely unknown. Carriage of plasmids generally confers substantial fitness costs, implying that for the plasmid-carrying bacteria to be maintained in the population, the plasmid cost needs to be balanced by a selective pressure conferred by, for example, antibiotics or heavy metals. We studied the effects of low levels of antibiotics and heavy metals on the selective maintenance of a 220-kbp extended-spectrum β-lactamase (ESBL) plasmid identified in a hospital outbreak of Klebsiella pneumoniae and Escherichia coli. The concentrations of antibiotics and heavy metals required to maintain plasmid-carrying bacteria, the minimal selective concentrations (MSCs), were in all cases below (almost up to 140-fold) the MIC of the plasmid-free susceptible bacteria. This finding indicates that the very low antibiotic and heavy metal levels found in polluted environments and in treated humans and animals might be sufficiently high to maintain multiresistance plasmids. When resistance genes were moved from the plasmid to the chromosome, the MSC decreased, showing that MSC for a specific resistance conditionally depends on genetic context. This finding suggests that a cost-free resistance could be maintained in a population by an infinitesimally low concentration of antibiotic. By studying the effect of combinations of several compounds, it was observed that for certain combinations of drugs each new compound added lowered the minimal selective concentration of the others. This combination effect could be a significant factor in the selection of multidrug resistance plasmids/bacterial clones in complex multidrug environments. Importance: Antibiotic resistance is in many pathogenic bacteria caused by genes that are carried on large conjugative plasmids. These plasmids typically contain multiple antibiotic resistance genes as well as genes that confer resistance to

  10. A New High-Level Gentamicin Resistance Gene, aph(2")-Id, in Enterococcus spp.

    PubMed Central

    Tsai, Shane F.; Zervos, Marcus J.; Clewell, Don B.; Donabedian, Susan M.; Sahm, Daniel F.; Chow, Joseph W.

    1998-01-01

    Enterococcus casseliflavus UC73 is a clinical blood isolate with high-level resistance to gentamicin. DNA preparations from UC73 failed to hybridize with intragenic probes for aac(6′)-Ie-aph(2")-Ia and aph(2")-Ic. A 4-kb fragment from UC73 was cloned and found to confer resistance to gentamicin in Escherichia coli DH5α transformants. Nucleotide sequence analysis revealed the presence of a 906-bp open reading frame whose deduced amino acid sequence had a region with homology to the aminoglycoside-modifying enzyme APH(2")-Ic and to the C-terminal domain of the bifunctional enzyme AAC(6′)-APH(2"). The gene is designated aph(2")-Id, and its observed phosphotransferase activity is designated APH(2")-Id. A PCR-generated intragenic probe hybridized to the genomic DNA from 17 of 118 enterococcal clinical isolates (108 with high-level gentamicin resistance) from five hospitals. All 17 were vancomycin-resistant Enterococcus faecium isolates, and pulsed-field typing revealed three distinct clones. The combination of ampicillin plus either amikacin or neomycin exhibited synergistic killing against E. casseliflavus UC73. Screening and interpretation of high-level aminoglycoside resistance in enterococci may need to be modified to include detection of APH(2")-Id. PMID:9593155

  11. High-Level Vancomycin-Resistant Staphylococcus aureus Isolates Associated with a Polymicrobial Biofilm▿

    PubMed Central

    Weigel, Linda M.; Donlan, Rodney M.; Shin, Dong Hyeon; Jensen, Bette; Clark, Nancye C.; McDougal, Linda K.; Zhu, Wenming; Musser, Kimberlee A.; Thompson, Jill; Kohlerschmidt, Donna; Dumas, Nellie; Limberger, Ronald J.; Patel, Jean B.

    2007-01-01

    Glycopeptides such as vancomycin are the treatment of choice for infections due to methicillin-resistant Staphylococcus aureus. This study describes the identification of high-level vancomycin-resistant S. aureus (VRSA) isolates in a polymicrobial biofilm within an indwelling nephrostomy tube in a patient in New York. S. aureus, Enterococcus faecalis, Enterococcus faecium, Micrococcus species, Morganella morganii, and Pseudomonas aeruginosa were isolated from the biofilm. For VRSA isolates, vancomycin MICs ranged from 32 to >128 μg/ml. VRSA isolates were also resistant to aminoglycosides, fluoroquinolones, macrolides, penicillin, and tetracycline but remained susceptible to chloramphenicol, linezolid, rifampin, and trimethoprim-sulfamethoxazole. The vanA gene was localized to a plasmid of ∼100 kb in VRSA and E. faecium isolates from the biofilm. Plasmid analysis revealed that the VRSA isolate acquired the 100-kb E. faecium plasmid, which was then maintained without integration into the MRSA plasmid. The tetracycline resistance genes tet(U) and tet(S), not previously detected in S. aureus isolates, were identified in the VRSA isolates. Additional resistance elements in the VRSA isolate included a multiresistance gene cluster, ermB-aadE-sat4-aphA-3, msrA (macrolide efflux), and the bifunctional aminoglycoside resistance gene aac(6′)-aph(2")-Ia. Multiple combinations of resistance genes among the various isolates of staphylococci and enterococci, including vanA, tet(S), and tet(U), illustrate the dynamic nature of gene acquisition and loss within and between bacterial species throughout the course of infection. The potential for interspecies transfer of antimicrobial resistance genes, including resistance to vancomycin, may be enhanced by the microenvironment of a biofilm. PMID:17074796

  12. Rapid Induction of High-Level Carbapenem Resistance in Heteroresistant KPC-Producing Klebsiella pneumoniae

    PubMed Central

    Adams-Sapper, Sheila; Nolen, Shantell; Donzelli, Grace Fox; Lal, Mallika; Chen, Kunihiko; Justo da Silva, Livia Helena; Moreira, Beatriz M.

    2015-01-01

    Enterobacteriaceae strains producing the Klebsiella pneumoniae carbapenemase (KPC) have disseminated worldwide, causing an urgent threat to public health. KPC-producing strains often exhibit low-level carbapenem resistance, which may be missed by automated clinical detection systems. In this study, eight Klebsiella pneumoniae strains with heterogeneous resistance to imipenem were used to elucidate the factors leading from imipenem susceptibility to high-level resistance as defined by clinical laboratory testing standards. Time-kill analysis with an inoculum as low as 3 × 106 CFU/ml and concentrations of imipenem 8- and 16-fold higher than the MIC resulted in the initial killing of 99.9% of the population. However, full recovery of the population occurred by 20 h of incubation in the same drug concentrations. Population profiles showed that recovery was mediated by a heteroresistant subpopulation at a frequency of 2 × 10−7 to 3 × 10−6. Samples selected 2 h after exposure to imipenem were as susceptible as the unexposed parental strain and produced the major outer membrane porin OmpK36. However, between 4 to 8 h after exposure, OmpK36 became absent, and the imipenem MIC increased at least 32-fold. Individual colonies isolated from cultures after 20 h of exposure revealed both susceptible and resistant subpopulations. Once induced, however, the high-level imipenem resistance was maintained, and OmpK36 remained unexpressed even without continued carbapenem exposure. This study demonstrates the essential coordination between blaKPC and ompK36 expression mediating high-level imipenem resistance from a population of bacteria that initially exhibits a carbapenem-susceptibility phenotype. PMID:25801565

  13. Mutations in the aph(2")-Ic Gene Are Responsible for Increased Levels of Aminoglycoside Resistance

    PubMed Central

    Lee, Hae Kyung; Vakulenko, Sergei B.; Clewell, Don B.; Lerner, Stephen A.; Chow, Joseph W.

    2002-01-01

    Random PCR mutagenesis of the enterococcal aph(2")-Ic gene followed by selection for mutant enzymes that confer enhanced levels of aminoglycoside resistance resulted in mutants of APH(2")-Ic with His-258-Leu and Phe-108-Leu substitutions, all of which conferred rises in the MICs of several aminoglycosides. The mutated residues are located outside conserved regions of aminoglycoside phosphotransferases. PMID:12234853

  14. High-Level Nickel Resistance in Alcaligenes xylosoxydans 31A and Alcaligenes eutrophus KTO2

    PubMed Central

    Schmidt, Thomas; Stoppel, Ralf-D.; Schlegel, Hans G.

    1991-01-01

    Two new nickel-resistant strains of Alcaligenes species were selected from a large number (about 400) of strains isolated from ecosystems polluted by heavy metals and were studied on the physiological and molecular level. Alcaligenes xylosoxydans 31A is a heterotrophic bacterium, and Alcaligenes eutrophus KTO2 is an autotrophic aerobic hydrogen-oxidizing bacterium. Both strains carry—among other plasmids—a megaplasmid determining resistance to 20 to 50 mM NiCl2 and 20 mM CoCl2 (when growing in defined Tris-buffered media). Megaplasmids pTOM8, pTOM9 from strain 31A, and pGOE2 from strain KTO2 confer nickel resistance to the same degree to transconjugants of all strains of A. eutrophus tested but were not transferred to Escherichia coli. However, DNA fragments carrying the nickel resistance genes, cloned into broad-hostrange vector pVDZ'2, confer resistance to A. eutrophus derivatives as well as E. coli. The DNA fragments of both bacteria, TBA8, TBA9, and GBA (14.5-kb BamHI fragments), appear to be identical. They share equal size, restriction maps, and strong DNA homology but are largely different from fragment HKI of nickel-cobalt resistance plasmid pMOL28 of A. eutrophus CH34. Images PMID:16348590

  15. Assessment of pheromone response in biofilm forming clinical isolates of high level gentamicin resistant Enterococcus faecalis.

    PubMed

    Jayanthi, S; Ananthasubramanian, M; Appalaraju, B

    2008-01-01

    Twenty five clinical isolates of high level gentamicin resistant Enterococcus faecalis were tested for their biofilm formation and pheromone responsiveness. The biofilm assay was carried out using microtiter plate method. Two isolates out of the 25 (8%) were high biofilm formers and 19 (76%) and four (16%) isolates were moderate and weak biofilm formers respectively. All the isolates responded to pheromones of E. faecalis FA2-2 strain. On addition of pheromone producing E. faecalis FA2-2 strain to these isolates, seven of 19 (37%) moderate biofilm formers developed into high biofilm formers. Similarly one of the 4 (25%) weak biofilm formers developed into high level biofilm former. Twelve (48%) of the 25 isolates were transconjugated by cross streak method using gentamicin as selective marker. This proves that the genetic factor for gentamicin resistance is present in the pheromone responsive plasmid. Among these twelve transaconjugants, seven isolates and one isolate were high biofilm formers on addition of E. faecalis FA2-2 and prior to its addition respectively. Out of the total 25 isolates, eight transconjugants for gentamicin resistance could turn to high biofilm formers on addition of the pheromone producing strain. All the isolates were resistant to more than two antibiotics tested. All the isolates were sensitive to vancomycin. The results indicate the significance of this nosocomial pathogen in biofilm formation and the role of pheromone responding clinical isolates of E. faecalis in spread of multidrug resistance genes.

  16. High level methicillin resistance correlates with reduced Staphylococcus aureus endothelial cell damage.

    PubMed

    Seidl, Kati; Leemann, Michèle; Palheiros Marques, Miguel; Rachmühl, Carole; Leimer, Nadja; Andreoni, Federica; Achermann, Yvonne; Zinkernagel, Annelies S

    2017-01-01

    There has been controversy about the intrinsic virulence of methicillin-resistant Staphylococcus aureus (MRSA) as compared to methicillin-susceptible S. aureus (MSSA). To address this discrepancy, the intrinsic virulence of 42 MRSA and 40 MSSA clinical isolates was assessed by testing endothelial cell (EC) damage, a surrogate marker for virulence in blood stream infections. Since these clinical isolates represent a heterogeneous group, well characterized S. aureus laboratory strains with SCCmec loss- and gain-of-function mutations were used in addition. The clinical MRSA isolates carrying typical hospital acquired SCCmec types (I, II or III) induced significantly less damage (47.8%) as compared to isolates with other SCCmec types (62.3%, p=0.03) and MSSA isolates (64.2%, p<0.01). There was a strong inverse correlation between high-level oxacillin resistance and low EC damage induction (R(2)=0.4464, p<0.001). High-level oxacillin resistant strains (MIC >32μ/ml) grew significantly slower as compared to isolates with low-level resistance (p=0.047). The level of EC damage positively correlated with α- and δ-toxin production (p<0.0001 and p<0.05, respectively) but not with β-toxin production. Invasive MRSA isolates (n=21, 56.3%) were significantly less cytotoxic as compared to invasive MSSA isolates (n=20, 68.0%, p<0.05). There was no difference between EC damage induced by superficial versus invasive isolates in either MRSA or MSSA strains. Our data suggest that the intrinsic virulence of MRSA is similar or even reduced as compared to MSSA strains but is linked to the level of methicillin resistance.

  17. Broad-Spectrum Transgenic Resistance against Distinct Tospovirus Species at the Genus Level

    PubMed Central

    Raja, Joseph A. J.; Yang, Ching-Fu; Chien, Wan-Chu; Lin, Chen-Hsuan; Liu, Fang-Lin; Wu, Hui-Wen; Yeh, Shyi-Dong

    2014-01-01

    Thrips-borne tospoviruses cause severe damage to crops worldwide. In this investigation, tobacco lines transgenic for individual WLm constructs containing the conserved motifs of the L RNA-encoded RNA-dependent RNA polymerase (L) gene of Watermelon silver mottle virus (WSMoV) were generated by Agrobacterium-mediated transformation. The WLm constructs included: (i) translatable WLm in a sense orientation; (ii) untranslatable WLmt with two stop codons; (iii) untranslatable WLmts with stop codons and a frame-shift; (iv) untranslatable antisense WLmA; and (v) WLmhp with an untranslatable inverted repeat of WLm containing the tospoviral S RNA 3′-terminal consensus sequence (5′-ATTGCTCT-3′) and an NcoI site as a linker to generate a double-stranded hairpin transcript. A total of 46.7–70.0% transgenic tobacco lines derived from individual constructs showed resistance to the homologous WSMoV; 35.7–100% plants of these different WSMoV-resistant lines exhibited broad-spectrum resistance against four other serologically unrelated tospoviruses Tomato spotted wilt virus, Groundnut yellow spot virus, Impatiens necrotic spot virus and Groundnut chlorotic fan-spot virus. The selected transgenic tobacco lines also exhibited broad-spectrum resistance against five additional tospoviruses from WSMoV and Iris yellow spot virus clades, but not against RNA viruses from other genera. Northern analyses indicated that the broad-spectrum resistance is mediated by RNA silencing. To validate the L conserved region resistance in vegetable crops, the constructs were also used to generate transgenic tomato lines, which also showed effective resistance against WSMoV and other tospoviruses. Thus, our approach of using the conserved motifs of tospoviral L gene as a transgene generates broad-spectrum resistance against tospoviruses at the genus level. PMID:24811071

  18. High-level fluoroquinolone resistance in Streptococcus pneumoniae requires mutations in parC and gyrA.

    PubMed Central

    Janoir, C; Zeller, V; Kitzis, M D; Moreau, N J; Gutmann, L

    1996-01-01

    The mechanism of high-level fluoroquinolone resistance was studied in strains of Streptococcus pneumoniae, either selected in vitro or isolated from clinical samples. By using DNA from these high-level-resistant strains, low-level-resistant transformants (MIC of pefloxacin, > or = 32 micrograms/ml; MIC of ciprofloxacin, 4 micrograms/ml; MIC of sparfloxacin, 0.50 micrograms/ml) were obtained at high frequencies (ca.10(-2)), while high-level-resistant transformants (MIC of pefloxacin, > or = 64 micrograms/ml; MIC of ciprofloxacin, 16 to 64 micrograms/ml; MIC of sparfloxacin, > or = 8 micrograms/ml) were obtained only at low frequencies (ca.10(-4)). This suggested that mutations in at least two unlinked genes were necessary to obtain high-level resistance. Low-level resistance was associated with ParC mutations (change from Ser to Tyr at position 79 [Ser79Tyr], Ser79Phe, or Asp83Gly). ParC mutations were associated, in high-level-resistant strains and transformants, with alterations in the quinolone resistance-determining region of GyrA (Ser84Tyr, Ser84Phe, and/or Glu88Lys). Low-level resistance was shown to be necessary for expression of the gyrA mutations. No mutation in the region corresponding to the quinolone resistance-determining region of GyrB and no alteration of drug accumulation were found. PMID:9124836

  19. A new low voltage level-shifted FVF current mirror with enhanced bandwidth and output resistance

    NASA Astrophysics Data System (ADS)

    Aggarwal, Bhawna; Gupta, Maneesha; Gupta, Anil Kumar; Sangal, Ankur

    2016-10-01

    This paper proposes a new high-performance level-shifted flipped voltage follower (LSFVF) based low-voltage current mirror (CM). The proposed CM utilises the low-supply voltage and low-input resistance characteristics of a flipped voltage follower (FVF) CM. In the proposed CM, level-shifting configuration is used to obtain a wide operating current range and resistive compensation technique is employed to increase the operating bandwidth. The peaking in frequency response is reduced by using an additional large MOSFET. Moreover, a very high output resistance (in GΩ range) along with low-current transfer error is achieved through super-cascode configuration for a wide current range (0-440 µA). Small signal analysis is carried out to show the improvements achieved at each step. The proposed CM is simulated by Mentor Graphics Eldospice in TSMC 0.18 µm CMOS, BSIM3 and Level 53 technology. In the proposed CM, a bandwidth of 6.1799 GHz, 1% settling time of 0.719 ns, input and output resistances of 21.43 Ω and 1.14 GΩ, respectively, are obtained with a single supply voltage of 1 V. The layout of the proposed CM has been designed and post-layout simulation results have been shown. The post-layout simulation results for Monte Carlo and temperature analysis have also been included to show the reliability of the CM against the variations in process parameters and temperature changes.

  20. High levels of inflammation and insulin resistance in obstructive sleep apnea patients with hypertension.

    PubMed

    Qian, Xiaoshun; Yin, Tong; Li, Tianzhi; Kang, Chunyan; Guo, Ruibiao; Sun, Baojun; Liu, Changting

    2012-08-01

    Hypertension induced by obstructive sleep apnea (OSA) may be multifactorial in origin, and systemic inflammation is one of the major factors. However, OSA patients do not always have the identical probability with hypertension even in patients with the same history and degree of OSA. The aim of this study was to compare the levels of inflammation and insulin resistance in two groups of patients who had the same degree as well as the same long history of OSA, but with/without hypertension. OSA patients (Apnea Hyponea Index, AHI ≥ 40/h, n = 70) were examined by polysomnography and blood analysis for the measurements of fasting plasma glucose, serum insulin (FINS), high-sensitivity C-reactive protein (CRP), peptide C,TNF-α, IL-6, and IL-10. Patients with hypertension (n = 40) had higher level of LDL-C and lower HDL-C levels than patients without hypertension. Almost half (16/40) of OSA patients with hypertension had family history of hypertension. Moreover in OSA patients with hypertension, the levels of TNF-α, IL-6, and CRP were higher, but IL-10 was lower than those without hypertension. FINS, peptide C, HOMA-IR, and HOMA-islet were also higher in OSA patients with hypertension. OSA patients with hypertension have higher level of inflammation and insulin resistance. Systemic inflammation and insulin resistance are both important factors for the development of hypertension in OSA patients.

  1. High-level aminoglycoside resistance and virulence characteristics among Enterococci isolated from recreational beaches in Malaysia.

    PubMed

    Dada, Ayokunle Christopher; Ahmad, Asmat; Usup, Gires; Heng, Lee Yook; Hamid, Rahimi

    2013-09-01

    We report the first study on the occurrence of high-level aminoglycoside-resistant (HLAR) Enterococci in coastal bathing waters and beach sand in Malaysia. None of the encountered isolates were resistant to high levels of gentamicin (500 μg/mL). However, high-level resistance to kanamycin (2,000 μg/mL) was observed in 14.2 % of tested isolates, the highest proportions observed being among beach sand isolates. High-level resistance to kanamycin was higher among Enterococcus faecalis and Enterococcus faecium than Enterococcus spp. Chi-square analysis showed no significant association between responses to tested antibiotics and the species allocation or source of isolation of all tested Enterococci. The species classification of encountered Enterococci resistance to vancomycin was highest among Enterococcus spp. (5.89 %) followed by E. faecium (4.785) and least among E. faecalis. A total of 160 isolates were also tested for virulence characteristics. On the whole, caseinase production was profoundly highest (15.01 %) while the least prevalent virulence characteristic observed among tested beach Enterococci was haemolysis of rabbit blood (3.65 %). A strong association was observed between the source of isolation and responses for each of caseinase (C = 0.47, V = 0.53) and slime (C = 0.50, V = 0.58) assays. Analysis of obtained spearman's coefficient showed a strong correlation between caseinase and each of the slime production (p = 0.04), gelatinase (p = 0.0035) and haemolytic activity on horse blood (p = 0.004), respectively. Suggestively, these are the main virulent characteristics of the studied beach Enterococci. Our findings suggest that recreational beaches may contribute to the dissemination of Enterococci with HLAR and virulence characteristics.

  2. Level of CYP4G19 Expression Is Associated with Pyrethroid Resistance in Blattella germanica.

    PubMed

    Guo, Guang-Zhou; Geng, Yi-Jie; Huang, Da-Na; Xue, Cai-Fang; Zhang, Ren-Li

    2010-01-01

    German cockroaches have become a large problem in the Shenzhen area because of their pesticide resistance, especially to pyrethroid. A pyrethroid called "Jia Chong Qing" to prevent pests for a long time were found to be resistant to "Jia Chong Qing" with resistance index of 3.88 measured using RT-PCR and immunohistochemistry analysis showed that both CYP4G19 mRNA and CYP4G19 protein expression levels in the wild strain were substantially higher than that of a sensitive strain. dsRNA segments derived from the target gene CYP4G19 were prepared using in vitro transcription and were microinjected into abdomens of the wild strain. Two to eight days after injection, the result showed that CYP4G19 mRNA expressions were significantly reduced in the groups injected with dsRNAs.

  3. Interface-induced two-step RESET for filament-based multi-level resistive memory

    NASA Astrophysics Data System (ADS)

    Yuan, Fang; Shen, Shanshan; Zhang, Zhigang; Pan, Liyang; Xu, Jun

    2016-03-01

    In this paper, a two-step RESET switching behavior of Ag/Al2O3/HfO2/Pt bilayer resistive random access memory (RRAM) devices is investigated. The interface between the two oxide layers is responsible for the special two-step RESET switching. When the conducting filaments have ruptured in the lower layer, the interface can protect the Ag ions of the filaments from breaking in the upper layer due to the trapped charges or defects at the interface. Therefore, a stable middle resistance state (MRS) is realized and the device exhibits a terrace-like I-V curve during the RESET operations. A filament-based switching mechanism combined with the electron hopping theory is proposed to explain the physical nature of the two-step RESET behavior. Furthermore, a good multi-level resistive switching performance with excellent endurance and retention reliability is obtained.

  4. Sampling and Pooling Methods for Capturing Herd Level Antibiotic Resistance in Swine Feces using qPCR and CFU Approaches.

    PubMed

    Schmidt, Gunilla Veslemøy; Mellerup, Anders; Christiansen, Lasse Engbo; Ståhl, Marie; Olsen, John Elmerdahl; Angen, Øystein

    2015-01-01

    The aim of this article was to define the sampling level and method combination that captures antibiotic resistance at pig herd level utilizing qPCR antibiotic resistance gene quantification and culture-based quantification of antibiotic resistant coliform indicator bacteria. Fourteen qPCR assays for commonly detected antibiotic resistance genes were developed, and used to quantify antibiotic resistance genes in total DNA from swine fecal samples that were obtained using different sampling and pooling methods. In parallel, the number of antibiotic resistant coliform indicator bacteria was determined in the same swine fecal samples. The results showed that the qPCR assays were capable of detecting differences in antibiotic resistance levels in individual animals that the coliform bacteria colony forming units (CFU) could not. Also, the qPCR assays more accurately quantified antibiotic resistance genes when comparing individual sampling and pooling methods. qPCR on pooled samples was found to be a good representative for the general resistance level in a pig herd compared to the coliform CFU counts. It had significantly reduced relative standard deviations compared to coliform CFU counts in the same samples, and therefore differences in antibiotic resistance levels between samples were more readily detected. To our knowledge, this is the first study to describe sampling and pooling methods for qPCR quantification of antibiotic resistance genes in total DNA extracted from swine feces.

  5. Correlation between plasma component levels of cultured fish and resistance to bacterial infection

    USGS Publications Warehouse

    Maita, M.; Satoh, K.-I.; Fukuda, Y.; Lee, H.-K.; Winton, J.R.; Okamoto, N.

    1998-01-01

    Mortalities of yellowtail Seriola quinqueradiata artificially infected with Lactococcus garvieae and of rainbow trout Oncorhynchus mykiss artificially infected with Vibrio anguillarum were compared with the levels of plasma components measured prior to challenge. The levels of plasma total cholesterol, free cholesterol and phospholipid of fish surviving infection were significantly higher in both yellowtail and rainbow trout than those of fish which died during the challenge test. Mortality of yellowtail with plasma total cholesterol levels lower than 250 mg/100 ml was significantly higher than that of fish which had cholesterol levels higher than 275 mg/100 ml (p < 0.05). Rainbow trout whose cholesterol was lower than 520 mg/100 ml suffered a significantly higher mortality due to vibriosis than fish having cholesterol levels higher than 560 mg/100 ml (p < 0.005). These results indicate that low levels of plasma lipid components may be an indicator of lowered disease resistance in cultured fish.

  6. Fitness costs associated with low-level dimethoate resistance in Phytoseiulus macropilis.

    PubMed

    Rezende, D D M; Fadini, M A M; Oliveira, H G; Oliveira, C M; Melo, J W S; Guedes, R N C; Pallini, A

    2013-07-01

    Phytoseiulus macropilis Banks (Acari: Phytoseiidae) is an effective predator of tetranychid mites, but there are no data on its response to pesticides. We investigated the resistance of the predatory mite P. macropilis to the acaricides abamectin and dimethoate, and we examined the fitness costs associated with resistance. Two populations were tested: one from conventional cultivation and another from an area not commercially exploited. After the application of acaricides to the predator, we determined the lethal effects of the acaricides, the instantaneous rate of population increase (r(i)), the predation on Tetranychus urticae Koch (Acari: Tetranychidae) and its ability to locate prey in an olfactometer. P. macropilis exhibited resistance to dimethoate only. The low level of resistance (9.4x) of the predator did not affect their ability to locate prey. However, the dimethoate resistant population was not as effective in contatining prey population when in lower density and exhibited a more pronounced decrease of r(i) in the presence of this acaricide, due to the reduced oviposition of the predator, a likely consequence of the different genetic background of this population.

  7. An explanation of resisted discoveries based on construal-level theory.

    PubMed

    Fang, Hui

    2015-02-01

    New discoveries and theories are crucial for the development of science, but they are often initially resisted by the scientific community. This paper analyses resistance to scientific discoveries that supplement previous research results or conclusions with new phenomena, such as long chains in macromolecules, Alfvén waves, parity nonconservation in weak interactions and quasicrystals. Construal-level theory is used to explain that the probability of new discoveries may be underestimated because of psychological distance. Thus, the insufficiently examined scope of an accepted theory may lead to overstating the suitable scope and underestimating the probability of its undiscovered counter-examples. Therefore, psychological activity can result in people instinctively resisting new discoveries. Direct evidence can help people judge the validity of a hypothesis with rational thinking. The effects of authorities and textbooks on the resistance to discoveries are also discussed. From the results of our analysis, suggestions are provided to reduce resistance to real discoveries, which will benefit the development of science.

  8. Line Profile Measurements of Atomic Oxygen at 1300 A with a VUV Raman Shifter

    NASA Technical Reports Server (NTRS)

    Sharma, Surendra P.; Exberger, Richard J.; Meyer, Scott A.; Gilmore, John O.

    1994-01-01

    We are currently developing an atomic oxygen diagnostic to study the degree of oxygen dissociation in ground-based facilities. The absorption of the (sub 3)P - (sup 3)S(sup 0) resonance triplet in the vacuum ultraviolet is a direct measure of the ground state number density of atomic oxygen. Although the integrated line strength is well known for these transitions, the line profile is not. We report the results of a series of experiments in which the line profile is measured in shock-heated oxygen. An ArF excimer laser and a hydrogen Raman shifter generate tunable VUV radiation at the resonance wavelength. The test gas is dissociated oxygen, generated in the Electric Arc Shock Tube (EAST) Facility at NASA-Ames Research Center. By measuring the absorption of known concentrations of atomic oxygen, we are able to study the absorption line profile. The results will serve as a calibration to apply this diagnostic in other flowfields.

  9. Broadband, Low-Loss Phase Shifters Based on Thin Ferroelectric Films

    NASA Technical Reports Server (NTRS)

    Romanofsky, Robert

    2004-01-01

    Several different types of microwave transmission line phase shifters based on thin ferroelectic films have been developed at the NASA Glenn Research Center. These include a series of coupled microstrip lines, slotline incorporating Marchand balms, odd-mode coplanar strips, and hybrid devices incorporating a switch to toggle the output termination between an open and virtual short circuit. A review of the theory of operation of each of these devices will be presented along with measured performance. Also, devices of the first variety have been subjected to total dose (proton) radiation exposure using a 200 MeV beam energy with a total dose up to nearly 1 kRad (Si). Results of these radiation tests will be discussed.

  10. A high linearity X-band SOI CMOS digitally-controlled phase shifter

    NASA Astrophysics Data System (ADS)

    Liang, Chen; Xinyu, Chen; Youtao, Zhang; Zhiqun, Li; Lei, Yang

    2015-06-01

    This paper proposed an X-band 6-bit passive phase shifter (PS) designed in 0.18 μm silicon-on-insulator (SOI) CMOS technology, which solves the key problem of high integration degree, low power, and a small size T/R module. The switched-topology is employed to achieve broadband and flat phase shift. The ESD circuit and driver are also integrated in the PS. It covers the frequency band from 7.5 to 10.5 GHz with an EMS phase error less than 7.5°. The input and output VSWRs are less than 2 and the insertion loss (IL) is between 8-14 dB across the 7.5 to 10.5 GHz, with a maximum IL difference of 4 dB. The input 1 dB compression point (IP1dB) is 20 dBm.

  11. Selection of a Multidrug Resistance Plasmid by Sublethal Levels of Antibiotics and Heavy Metals

    PubMed Central

    Gullberg, Erik; Albrecht, Lisa M.; Karlsson, Christoffer; Sandegren, Linus

    2014-01-01

    ABSTRACT How sublethal levels of antibiotics and heavy metals select for clinically important multidrug resistance plasmids is largely unknown. Carriage of plasmids generally confers substantial fitness costs, implying that for the plasmid-carrying bacteria to be maintained in the population, the plasmid cost needs to be balanced by a selective pressure conferred by, for example, antibiotics or heavy metals. We studied the effects of low levels of antibiotics and heavy metals on the selective maintenance of a 220-kbp extended-spectrum β-lactamase (ESBL) plasmid identified in a hospital outbreak of Klebsiella pneumoniae and Escherichia coli. The concentrations of antibiotics and heavy metals required to maintain plasmid-carrying bacteria, the minimal selective concentrations (MSCs), were in all cases below (almost up to 140-fold) the MIC of the plasmid-free susceptible bacteria. This finding indicates that the very low antibiotic and heavy metal levels found in polluted environments and in treated humans and animals might be sufficiently high to maintain multiresistance plasmids. When resistance genes were moved from the plasmid to the chromosome, the MSC decreased, showing that MSC for a specific resistance conditionally depends on genetic context. This finding suggests that a cost-free resistance could be maintained in a population by an infinitesimally low concentration of antibiotic. By studying the effect of combinations of several compounds, it was observed that for certain combinations of drugs each new compound added lowered the minimal selective concentration of the others. This combination effect could be a significant factor in the selection of multidrug resistance plasmids/bacterial clones in complex multidrug environments. PMID:25293762

  12. Native plant diversity resists invasion at both low and high resource levels.

    PubMed

    Maron, John; Marler, Marilyn

    2007-10-01

    Human modification of the environment is causing both loss of species and changes in resource availability. While studies have examined how species loss at the local level can influence invasion resistance, interactions between species loss and other components of environmental change remain poorly studied. In particular, the manner in which native diversity interacts with resource availability to influence invasion resistance is not well understood. We created experimental plant assemblages that varied in native species (1-16 species) and/or functional richness (defined by rooting morphology and phenology; one to five functional groups). We crossed these diversity treatments with resource (water) addition to determine their interactive effects on invasion resistance to spotted knapweed (Centaurea maculosa), a potent exotic invader in the intermountain West of the United States. We also determined how native diversity and resource addition influenced plant-available soil nitrogen, soil moisture, and light. Assemblages with lower species and functional diversity were more heavily invaded than assemblages with greater species and functional diversity. In uninvaded assemblages, experimental addition of water increased soil moisture and plant-available nitrogen and decreased light availability. The availability of these resources generally declined with increasing native plant diversity. Although water addition increased susceptibility to invasion, it did not fundamentally change the negative relationship between diversity and invasibility. Thus, native diversity provided strong invasion resistance even under high resource availability. These results suggest that the effects of local diversity can remain robust despite enhanced resource levels that are predicted under scenarios of global change.

  13. Antimicrobial resistance among Campylobacter spp. strains isolated from different poultry production systems at slaughterhouse level.

    PubMed

    Fraqueza, M J; Martins, A; Borges, A C; Fernandes, M H; Fernandes, M J; Vaz, Y; Bessa, R J B; Barreto, A S

    2014-06-01

    The aim of the current work was to evaluate the prevalence and antimicrobial susceptibility of Campylobacter spp. isolated from different chicken production systems at the slaughterhouse level. Chicken sampling at slaughterhouse was performed for cecum, carcass, and breast meat from flocks of organic (n = 6), extensive indoor (n = 14), and intensive production (n = 14), totaling 34 ceca pools, 64 neck skin pools, and 132 breasts, representing 96,386 chickens. A collection of 167 strains were identified as Campylobacter coli (n = 85) and Campylobacter jejuni (n = 82) and were tested for susceptibility to 11 antimicrobial agents by the disk diffusion method. The frequency of Campylobacter in chicken samples from different production systems was between 79 and 100%. Campylobacter isolated from all origins were resistant to the fluoroquinolones studied (80-98%). However, for ciprofloxacin and ofloxacin, the Campylobacter isolates from extensive indoor chicken were significantly (P < 0.05) less resistant (77 and 58%) than that from organic (97 and 91%) and intensive production (96 and 95%). A high probability of tetracycline resistance occurrence was also found for the Campylobacter spp. tested (58% for C. jejuni and 76% for C. coli). A more frequent profile of multidrug resistance was noticed for isolates from intensive and organic production than for extensive indoor production. These results reinforce the need of efficient strategy implementation to control and reduce Campylobacter in chickens at production and slaughter levels, and the necessity to reduce the use of antimicrobials in poultry sector.

  14. Frequency of biocide-resistant genes and susceptibility to chlorhexidine in high-level mupirocin-resistant, methicillin-resistant Staphylococcus aureus (MuH MRSA).

    PubMed

    Liu, Qingzhong; Zhao, Huanqiang; Han, Lizhong; Shu, Wen; Wu, Qiong; Ni, Yuxing

    2015-08-01

    The aim of this study was to determine the prevalence of biocide-resistant determinants and the susceptibility to chlorhexidine in high-level mupirocin-resistant, methicillin-resistant Staphylococcus aureus (MuH MRSA). Fifty-three MuH MRSA isolates were analyzed for plasmid-borne genes (qacA/B, smr, qacG, qacH, and qacJ) by polymerase chain reaction (PCR); for chromosome-mediated genes (norA, norB, norC, mepA, mdeA, sepA, and sdrM) by PCR and quantitative reverse transcription-PCR (qRT-PCR); and for susceptibility to chlorhexidine by MIC and minimum bactericidal concentration (MBC). Furthermore, disinfectant efficacy was tested in the presence of 3.0% bovine serum albumin (BSA) in MBC detection. The plasmid-borne genes qacA/B (83.0%) and smr (77.4%) and overexpressions of chromosome-mediated genes norA (49.0%) and norB (28.8%) were predominantly found in isolates studied, and 90.6% of the isolates revealed tolerance to chlorhexidine. In the presence of BSA, the average MBC of chlorhexidine for these isolates rose to 256 μg/mL. Altogether, our results suggest that surveillance of sensitivity to biocides among MuH MRSA isolates is essential for hospital infection control.

  15. Prevalence of Multidrug-resistant, Extensively Drug-resistant, and Pandrug-resistant Pseudomonas aeruginosa from a Tertiary Level Intensive Care Unit

    PubMed Central

    Gill, JS; Arora, Sunil; Khanna, SP; Kumar, KVS Hari

    2016-01-01

    Background: Infection by Pseudomonas aeruginosa is common in the Intensive Care Unit (ICU), leading to increased morbidity and mortality. The organism is classified into various phenotypes based on the drug resistance pattern, namely, drug-resistant (DR), multi-DR (MDR), extensively DR (XDR), and pan-DR (PDR). We aim to study the incidence of P. aeruginosa phenotypes in a tertiary level ICU. Materials and Methods: We conducted this prospective, observational study for 2 years (January 2014-December 2015) and collected appropriate clinical samples (blood, urine, wound discharge, etc.,) from all the patients admitted to ICU. We excluded patients with known septicemia and P. aeruginosa infection. Group 1 comprised a total 1915 patient samples and Group 2 comprised 100 active surveillance samples, collected from the medical staff and the hospital environment. The data were analyzed using appropriate statistical methods, and a P < 0.05 was considered statistically significant. Results: We isolated 597 pathogenic bacteria out of 1915 specimens, giving a culture positivity rate of 31.2%. Klebsiella (43%), Acinetobacter (22%), and P. aeruginosa (15%) were the top three isolated bacteria. None of the surveillance samples grew P. aeruginosa. Antibiotic resistance studies revealed that 47.7% of P. aeruginosa isolates were DR, 50% were MDR, and 2.3% were XDR phenotype. None of the strains showed PDR phenotype. Conclusion: Our data revealed a high prevalence of DR phenotypes of P. aeruginosa in the ICU. Judicious use of antibiotics and strict infection control measures are essential to reduce the prevalence of drug resistance. PMID:27942195

  16. RNA-Seq and molecular docking reveal multi-level pesticide resistance in the bed bug

    PubMed Central

    2012-01-01

    Background Bed bugs (Cimex lectularius) are hematophagous nocturnal parasites of humans that have attained high impact status due to their worldwide resurgence. The sudden and rampant resurgence of C. lectularius has been attributed to numerous factors including frequent international travel, narrower pest management practices, and insecticide resistance. Results We performed a next-generation RNA sequencing (RNA-Seq) experiment to find differentially expressed genes between pesticide-resistant (PR) and pesticide-susceptible (PS) strains of C. lectularius. A reference transcriptome database of 51,492 expressed sequence tags (ESTs) was created by combining the databases derived from de novo assembled mRNA-Seq tags (30,404 ESTs) and our previous 454 pyrosequenced database (21,088 ESTs). The two-way GLMseq analysis revealed ~15,000 highly significant differentially expressed ESTs between the PR and PS strains. Among the top 5,000 differentially expressed ESTs, 109 putative defense genes (cuticular proteins, cytochrome P450s, antioxidant genes, ABC transporters, glutathione S-transferases, carboxylesterases and acetyl cholinesterase) involved in penetration resistance and metabolic resistance were identified. Tissue and development-specific expression of P450 CYP3 clan members showed high mRNA levels in the cuticle, Malpighian tubules, and midgut; and in early instar nymphs, respectively. Lastly, molecular modeling and docking of a candidate cytochrome P450 (CYP397A1V2) revealed the flexibility of the deduced protein to metabolize a broad range of insecticide substrates including DDT, deltamethrin, permethrin, and imidacloprid. Conclusions We developed significant molecular resources for C. lectularius putatively involved in metabolic resistance as well as those participating in other modes of insecticide resistance. RNA-Seq profiles of PR strains combined with tissue-specific profiles and molecular docking revealed multi-level insecticide resistance in C. lectularius

  17. Abdominal Obesity and Insulin Resistance in People Exposed to Moderate-to-High Levels of Dioxin.

    PubMed

    Chang, Jung-Wei; Chen, Hsiu-Ling; Su, Huey-Jen; Lee, Ching-Chang

    2016-01-01

    Obesity, a risk factor for developing metabolic complications, is a major public health problem. Abdominal obesity is strongly accompanied by a cluster of metabolic abnormalities characterized by insulin resistance. The link between persistent organic pollutants (POPs) and insulin resistance has been investigated in animal and epidemiological studies. We aimed to examine whether insulin resistance is greater in people with abdominal obesity (AO) and concomitant exposure to serum dioxins (PCDD/Fs). We conducted a cross-sectional descriptive study of 2876 participants living near a PCDD/Fs contaminated area. Seventeen 2,3,7,8-substituted PCDD/Fs congeners were measured, and then the associations between the main predictor variable, serum TEQDF-1998, abdominal obesity (AO), dependent variables, and insulin resistance were examined. Twelve of the 17 congeners, widely distributed among PCDDs, and PCDFs, had trends for associations with abdominal adiposity. In men, the highest quintiles of 1,2,3,7,8-PeCDF; 1,2,3,7,8-PeCDD; 2,3,7,8-TCDD; 2,3,7,8-TCDF; and 2,3,4,7,8-PeCDF had the top five adjusted odds ratios (AORs) + 95% confidence intervals (CIs):[4.2; 2.7-6.4], [3.6; 2.3-5.7], [3.2; 2.1-5.0], [3.0; 2.0-4.5], and [2.9; 1.9-4.7], respectively. In women, the highest quintiles of 1,2,3,4,7,8,9-HpCDF; 1,2,3,6,7,8-HxCDF; and 1,2,3,4,6,7,8-HpCDF had the top three AORs + 95% CIs:[3.0; 1.9-4.7], [2.0; 1.3-3.1], and [1.9; 1.3-2.9], respectively. After confounding factors had been adjusted for, men, but not women, with higher serum TEQDF-1998 levels or abdominal obesity had a significantly (Ptrend < 0.001) greater risk for abnormal insulin resistance. The groups with the highest joint serum TEQDF-1998 and abdominal obesity levels were associated with elevated insulin resistance at 5.0 times the odds of the groups with the lowest joint levels (AOR 5.23; 95% CI: 3.53-7.77). We hypothesize that serum TEQDF-1998 and abdominal obesity affect the association with insulin resistance in

  18. Abdominal Obesity and Insulin Resistance in People Exposed to Moderate-to-High Levels of Dioxin

    PubMed Central

    Chang, Jung-Wei; Chen, Hsiu-Ling; Su, Huey-Jen; Lee, Ching-Chang

    2016-01-01

    Obesity, a risk factor for developing metabolic complications, is a major public health problem. Abdominal obesity is strongly accompanied by a cluster of metabolic abnormalities characterized by insulin resistance. The link between persistent organic pollutants (POPs) and insulin resistance has been investigated in animal and epidemiological studies. We aimed to examine whether insulin resistance is greater in people with abdominal obesity (AO) and concomitant exposure to serum dioxins (PCDD/Fs). We conducted a cross-sectional descriptive study of 2876 participants living near a PCDD/Fs contaminated area. Seventeen 2,3,7,8-substituted PCDD/Fs congeners were measured, and then the associations between the main predictor variable, serum TEQDF-1998, abdominal obesity (AO), dependent variables, and insulin resistance were examined. Twelve of the 17 congeners, widely distributed among PCDDs, and PCDFs, had trends for associations with abdominal adiposity. In men, the highest quintiles of 1,2,3,7,8-PeCDF; 1,2,3,7,8-PeCDD; 2,3,7,8-TCDD; 2,3,7,8-TCDF; and 2,3,4,7,8-PeCDF had the top five adjusted odds ratios (AORs) + 95% confidence intervals (CIs):[4.2; 2.7–6.4], [3.6; 2.3–5.7], [3.2; 2.1–5.0], [3.0; 2.0–4.5], and [2.9; 1.9–4.7], respectively. In women, the highest quintiles of 1,2,3,4,7,8,9-HpCDF; 1,2,3,6,7,8-HxCDF; and 1,2,3,4,6,7,8-HpCDF had the top three AORs + 95% CIs:[3.0; 1.9–4.7], [2.0; 1.3–3.1], and [1.9; 1.3–2.9], respectively. After confounding factors had been adjusted for, men, but not women, with higher serum TEQDF-1998 levels or abdominal obesity had a significantly (Ptrend < 0.001) greater risk for abnormal insulin resistance. The groups with the highest joint serum TEQDF-1998 and abdominal obesity levels were associated with elevated insulin resistance at 5.0 times the odds of the groups with the lowest joint levels (AOR 5.23; 95% CI: 3.53–7.77). We hypothesize that serum TEQDF-1998 and abdominal obesity affect the association with

  19. Antimicrobial susceptibility and mechanisms of high-level macrolide resistance in clinical isolates of Moraxella nonliquefaciens.

    PubMed

    Nonaka, Shotaro; Matsuzaki, Kosuke; Kazama, Tomoya; Nishiyama, Hiroyuki; Ida, Yoko; Koyano, Saho; Sonobe, Kazunari; Okamura, Noboru; Saito, Ryoichi

    2014-02-01

    We investigated antimicrobial susceptibility and the molecular mechanism involved in conferring high-level macrolide resistance in 47 clinical isolates of Moraxella nonliquefaciens from Japan. Antimicrobial susceptibility was determined using Etest and agar dilution methods. Thirty-two erythromycin-non-susceptible strains were evaluated for the possibility of clonal spreading, using PFGE. To analyse the mechanism related to macrolide resistance, mutations in the 23S rRNA gene and the ribosomal proteins, and the presence of methylase genes were investigated by PCR and sequencing. The efflux system was examined using appropriate inhibitors. Penicillin, ampicillin, amoxicillin, cefixime, levofloxacin and antimicrobials containing β-lactamase inhibitors showed strong activity against 47 M. nonliquefaciens isolates. Thirty-two (68.1 %) of the 47 isolates showed high-level MICs to macrolides (MIC ≥128 mg l(-1)) and shared the A2058T mutation in the 23S rRNA gene. The geometric mean MIC to macrolides of A2058T-mutated strains was significantly higher than that of WT strains (P<0.0001). Thirty-two isolates with high-level macrolide MICs clustered into 30 patterns on the basis of the PFGE dendrogram, indicating that the macrolide-resistant strains were not clonal. In contrast, no common mutations of the ribosomal proteins or methylase genes, or overproduction of the efflux system were observed in A2058T-mutated strains. Moreover, of the 47 M. nonliquefaciens strains, 43 (91.5 %) were bro-1 and 4 (8.5 %) were bro-2 positive. Our results suggest that most M. nonliquefaciens clinical isolates show high-level macrolide resistance conferred by the A2058T mutation in the 23S rRNA gene. This study represents the first characterization of M. nonliquefaciens.

  20. Molecular Correlates of High-Level Antifolate Resistance in Rwandan Children with Plasmodium falciparum Malaria▿

    PubMed Central

    Karema, Corine; Imwong, Mallika; Fanello, Caterina I.; Stepniewska, Kasia; Uwimana, Aline; Nakeesathit, Supatchara; Dondorp, Arjen; Day, Nicholas P.; White, Nicholas J.

    2010-01-01

    Antifolate drugs have an important role in the treatment of malaria. Polymorphisms in the genes encoding the dihydrofolate reductase and dihydropteroate synthetase enzymes cause resistance to the antifol and sulfa drugs, respectively. Rwanda has the highest levels of antimalarial drug resistance in Africa. We correlated the efficacy of chlorproguanil-dapsone plus artesunate (CPG-DDS+A) and amodiaquine plus sulfadoxine-pyrimethamine (AQ+SP) in children with uncomplicated malaria caused by Plasmodium falciparum parasites with pfdhfr and pfdhps mutations, which are known to confer reduced drug susceptibility, in two areas of Rwanda. In the eastern province, where the cure rates were low, over 75% of isolates had three or more pfdhfr mutations and two or three pfdhps mutations and 11% had the pfdhfr 164-Leu polymorphism. In the western province, where the cure rates were significantly higher (P < 0.001), the prevalence of multiple resistance mutations was lower and the pfdhfr I164L polymorphism was not found. The risk of treatment failure following the administration of AQ+SP more than doubled for each additional pfdhfr resistance mutation (odds ratio [OR] = 2.4; 95% confidence interval [CI] = 1.01 to 5.55; P = 0.048) and each pfdhps mutation (OR = 2.1; 95% CI = 1.21 to 3.54; P = 0.008). The risk of failure following CPG-DDS+A treatment was 2.2 times higher (95% CI = 1.34 to 3.7) for each additional pfdhfr mutation, whereas there was no association with mutations in the pfdhps gene (P = 0.13). The pfdhfr 164-Leu polymorphism is prevalent in eastern Rwanda. Antimalarial treatments with currently available antifol-sulfa combinations are no longer effective in Rwanda because of high-level resistance. PMID:19841150

  1. YM155 reverses cisplatin resistance in head and neck cancer by decreasing cytoplasmic survivin levels

    PubMed Central

    Kumar, Bhavna; Yadav, Arti; Lang, James C.; Cipolla, Michael; Schmitt, Alessandra C.; Arradaza, Nicole; Teknos, Theodoros N.; Kumar, Pawan

    2013-01-01

    Cisplatin is one of the commonly used chemotherapeutic drugs for the treatment of head and neck squamous cell carcinoma (HNSCC). However, acquisition of cisplatin resistance is common in patients with HNSCC and it often leads to local and distant failure. In this study, we demonstrate that survivin expression is significantly upregulated in HNSCC primary tumors and cell lines. In addition, survivin levels were significantly higher in HPV negative patients that normally respond poorly to cisplatin treatment. Survivin expression was further increased in cisplatin resistant cells (CAL27-CisR) as compared to its parent cells (CAL27). Therefore, we hypothesize that targeting of survivin in HNSCC could reverse the resistant phenotype in tumor cells thereby enhancing the therapeutic efficacy of cisplatin. We used both in vitro and in vivo models to test the efficacy of YM155, a small molecule survivin inhibitor, either as a single agent or in combination with cisplatin. YM155 significantly decreased survivin levels and cell proliferation in a dose-dependent manner. In addition, YM155 pretreatment significantly reversed cisplatin resistance in cancer cells. Interestingly, YM155 treatment altered the dynamic localization of survivin in cells by inducing a rapid reduction in cytoplasmic survivin, which plays a critical role in its anti-apoptotic function. In a SCID mouse xenograft model, YM155 significantly enhanced the anti-tumor and anti-angiogenic effects of cisplatin with no added systemic toxicity. Taken together, our results suggest a potentially novel strategy to use YM155 to overcome the resistance in tumor cells thereby enhancing the effectiveness of the chemotherapy in HNSCC. PMID:22723337

  2. High-Level Chromate Resistance in Arthrobacter sp. strain FB24 Requires Previously Uncharacterized Accessory Genes

    SciTech Connect

    Henne, Kristene L.; Nakatsu, Cindy N.; Thompson, Dorothea K.; Konopka, Allan

    2009-09-24

    The annotated genome sequence of Arthrobacter sp. strain FB24 revealed a chromate resistance determinant (CRD): a cluster of 8 genes located on a 10.6 kb fragment of a 96 kb plasmid. The CRD includes chrA, which encodes a putative chromate efflux protein, and three genes with amino acid similarities to the amino and carboxy termini of ChrB, a putative regulatory protein. There are also three novel genes that have not been previously associated with chromate resistance in other bacteria; they encode an oxidoreductase (most similar to malate:quinone oxidoreductase), a functionally unknown protein with a WD40 repeat domain and a lipoprotein. A chromate-sensitive mutant (strain D11) was generated by curing FB24 of its 96-kb plasmid. Elemental analysis indicated that chromate-exposed cells of strain D11 accumulated three times more chromium than strain FB24. Introduction of the CRD into strain D11 conferred chromate resistance comparable to wild-type levels, whereas deletion of specific regions of the CRD led to decreased resistance. Using real-time reverse transcriptase PCR, we show that expression of each gene within the CRD is specifically induced in response to chromate but not by lead, hydrogen peroxide or arsenate. Higher levels of chrA expression were achieved when the chrB orthologs and the WD40 repeat domain genes were present, suggesting their regulatory roles. Collectively, our findings indicate that chromate resistance in strain FB24 is primarily achieved by plasmid-mediated chromate efflux with the contribution of previously unrecognized accessory genes.

  3. Parasite resistance and tolerance in honeybees at the individual and social level.

    PubMed

    Kurze, Christoph; Routtu, Jarkko; Moritz, Robin F A

    2016-08-01

    Organisms living in large groups, such as social insects, are particularly vulnerable to parasite transmission. However, they have evolved diverse defence mechanisms which are not only restricted to the individual's immune response, but also include social defences. Here, we review cases of adaptations at the individual and social level in the honeybee Apis mellifera against the ectoparasitic mite Varroa destructor and the endoparasitic microsporidians Nosema ceranae and Nosema apis. They are considered important threats to honeybee health worldwide. We highlight how individual resistance may result in tolerance at the colony level and vice versa.

  4. Relationship among Periodontal Disease, Insulin Resistance, Salivary Cortisol, and Stress Levels during Pregnancy.

    PubMed

    Seraphim, Ana Paula Castilho Garcia; Chiba, Fernando Yamamoto; Pereira, Renato Felipe; Mattera, Maria Sara de Lima Coutinho; Moimaz, Suzely Adas Saliba; Sumida, Doris Hissako

    2016-01-01

    Pregnancy is a period involving important metabolic changes that enable the maintenance of the mother's health and development of the fetus. This study aimed to assess the relationship among periodontal disease, insulin resistance, salivary cortisol concentration and level of perceived stress in pregnant women. This was a cross-sectional study. The sample comprised 96 pregnant women between the fifth and seventh month of pregnancy registered at the Basic Health Units of the Unified Health System (SUS). The periodontal condition was assessed after obtainment free and informed consent from the participants. Participants were divided into three groups: control subjects with a healthy periodontal condition (CN; n=46), patients with gingivitis (GI; n=26), and patients with periodontitis (PI; n=24). Saliva and blood samples were collected for evaluation of salivary cortisol concentration, glycemia, insulinemia and Homeostasis Model Assessment-Insulin Resistance index. A validated survey for the assessment of perceived stress levels was also performed. PI group showed significantly higher (p<0.05) blood glucose levels (CN: 4.43±0.05; GI: 4.46±0.04; PI: 4.68±0.08), insulinemia (CN: 6.93±0.45; GI: 8.87±0.79; PI: 12.77±1.30), insulin resistance (CN: 1.40±0.10; GI: 1.81±0.18; PI: 2.66±0.29) compared with the CN and GI groups. The levels of perceived stress were higher (p<0.05) in PI and GI groups when compared to CN group (CN: 20.5±1.26; GI: 25.8±1.95; PI: 26.6±1.36). There was no significant difference in the concentration of salivary cortisol between the groups (CN: 11.13±0.58; GI: 11.96±0.74; PI: 11.47±0.74). It was concluded that there is a relationship between higher levels of perceived stress, insulin resistance and the occurrence of periodontal disease during pregnancy. This study emphasizes the importance of preventing periodontitis in order to avoid insulin resistance and stress during pregnancy since these can cause systemic complications for the

  5. Transgenic resistance confers effective field level control of bacterial spot disease in tomato.

    PubMed

    Horvath, Diana M; Stall, Robert E; Jones, Jeffrey B; Pauly, Michael H; Vallad, Gary E; Dahlbeck, Doug; Staskawicz, Brian J; Scott, John W

    2012-01-01

    We investigated whether lines of transgenic tomato (Solanum lycopersicum) expressing the Bs2 resistance gene from pepper, a close relative of tomato, demonstrate improved resistance to bacterial spot disease caused by Xanthomonas species in replicated multi-year field trials under commercial type growing conditions. We report that the presence of the Bs2 gene in the highly susceptible VF 36 background reduced disease to extremely low levels, and VF 36-Bs2 plants displayed the lowest disease severity amongst all tomato varieties tested, including commercial and breeding lines with host resistance. Yields of marketable fruit from transgenic lines were typically 2.5 times that of the non-transformed parent line, but varied between 1.5 and 11.5 fold depending on weather conditions and disease pressure. Trials were conducted without application of any copper-based bactericides, presently in wide use despite negative impacts on the environment. This is the first demonstration of effective field resistance in a transgenic genotype based on a plant R gene and provides an opportunity for control of a devastating pathogen while eliminating ineffective copper pesticides.

  6. Transgenic Resistance Confers Effective Field Level Control of Bacterial Spot Disease in Tomato

    PubMed Central

    Horvath, Diana M.; Stall, Robert E.; Jones, Jeffrey B.; Pauly, Michael H.; Vallad, Gary E.; Dahlbeck, Doug; Staskawicz, Brian J.; Scott, John W.

    2012-01-01

    We investigated whether lines of transgenic tomato (Solanum lycopersicum) expressing the Bs2 resistance gene from pepper, a close relative of tomato, demonstrate improved resistance to bacterial spot disease caused by Xanthomonas species in replicated multi-year field trials under commercial type growing conditions. We report that the presence of the Bs2 gene in the highly susceptible VF 36 background reduced disease to extremely low levels, and VF 36-Bs2 plants displayed the lowest disease severity amongst all tomato varieties tested, including commercial and breeding lines with host resistance. Yields of marketable fruit from transgenic lines were typically 2.5 times that of the non-transformed parent line, but varied between 1.5 and 11.5 fold depending on weather conditions and disease pressure. Trials were conducted without application of any copper-based bactericides, presently in wide use despite negative impacts on the environment. This is the first demonstration of effective field resistance in a transgenic genotype based on a plant R gene and provides an opportunity for control of a devastating pathogen while eliminating ineffective copper pesticides. PMID:22870280

  7. Characterisation of clinical meticillin-resistant Staphylococcus epidermidis demonstrating high levels of linezolid resistance (>256 μg/ml) resulting from transmissible and mutational mechanisms.

    PubMed

    Gabriel, Emma M; Fitzgibbon, Siobhan; Clair, James; Coffey, Aidan; O'Mahony, Jim M

    2015-07-01

    Staphylococcus epidermidis (S. epidermidis), one of the leading etiological agents of nosocomial infections poses a significant economic burden globally. Introduced in 2000, linezolid (LZD) has become an important antibiotic, used in nearly seventy countries worldwide to treat infections caused by Gram-positive pathogens such as meticillin-resistant Staphylococcus and Streptococcus species along with vancomycin-resistant enterococci. Resistance to LZD in clinical settings remains rare. Here, we report the emergence of meticillin resistant S. epidermidis (MRSE) clinical isolates from two voluntary general acute hospitals exhibiting higher than typically reported levels of LZD resistance (MIC>256 μg/ml). The MRSE ST-2 clone isolated from eight patients (2010-2011) not only possessed resistance-conferring mutations such as G2576T in domain V of 23S rRNA gene (as determined by HRM-PCR analysis) and R172C substitution in the ribosomal protein L3, but also carried the cfr gene (the only known transmissible mechanism of LZD resistance). All isolates possessed several key biofilm-associated genes (such as icaA, icaD, aap and atlE) and resistance to multiple clinically significant antibiotics was recorded. This study reports the earliest incidence (2010) of clinical MRSE in the Republic of Ireland demonstrating multiple LZD resistance mechanisms both mutational and potentially transmissible, and characterises this emerging resistance from a molecular perspective.

  8. Evaluation of levels of antibiotic resistance in groundwater-derived E. coli isolates in the Midwest of Ireland and elucidation of potential predictors of resistance

    NASA Astrophysics Data System (ADS)

    O'Dwyer, Jean; Hynds, Paul; Pot, Matthieu; Adley, Catherine C.; Ryan, Michael P.

    2017-02-01

    Antibiotic-resistant (pathogenic and non-pathogenic) organisms and genes are now acknowledged as significant emerging aquatic contaminants with potentially adverse human and ecological health impacts, and thus require monitoring. This study is the first to investigate levels of resistance among Irish groundwater (private wells) samples; Escherichia coli isolates were examined against a panel of commonly prescribed human and veterinary therapeutic antibiotics, followed by determination of the causative factors of resistance. Overall, 42 confirmed E. coli isolates were recovered from a groundwater-sampling cohort. Resistance to the human panel of antibiotics was moderate; nine (21.4%) E. coli isolates demonstrated resistance to one or more human antibiotics. Conversely, extremely high levels of resistance to veterinary antibiotics were found, with all isolates presenting resistance to one or more veterinary antibiotics. Particularly high levels of resistance (93%) were found with respect to the aminoglycoside class of antibiotics. Results of statistical analysis indicate a significant association between the presence of human (multiple) antibiotic resistance (p = 0.002-0.011) and both septic tank density and the presence of vulnerable sub-populations (<5 years). For the veterinary antibiotics, results point to a significant relationship (p = <0.001) between livestock (cattle) density and the prevalence of multiple antibiotic resistant E. coli. Groundwater continues to be an important resource in Ireland, particularly in rural areas; thus, results of this preliminary study offer a valuable insight into the prevalence of antibiotic resistance in the hydrogeological environment and establish a need for further research with a larger geological diversity.

  9. A K-Band Linear Phased Array Antenna Based on Ba(0.60)Sr(0.40)TiO3 Thin Film Phase Shifters

    NASA Technical Reports Server (NTRS)

    Romanofsky, R.; Bernhard, J.; Washington, G.; VanKeuls, F.; Miranda, F.; Cannedy, C.

    2000-01-01

    This paper summarizes the development of a 23.675 GHz linear 16-element scanning phased array antenna based on thin ferroelectric film coupled microstripline phase shifters and microstrip patch radiators.

  10. Higher copy numbers of the potato RB transgene correspond to enhanced transcript and late blight resistance levels.

    PubMed

    Bradeen, James M; Iorizzo, Massimo; Mollov, Dimitre S; Raasch, John; Kramer, Lara Colton; Millett, Benjamin P; Austin-Phillips, Sandra; Jiang, Jiming; Carputo, Domenico

    2009-04-01

    Late blight of potato ranks among the costliest of crop diseases worldwide. Host resistance offers the best means for controlling late blight, but previously deployed single resistance genes have been short-lived in their effectiveness. The foliar blight resistance gene RB, previously cloned from the wild potato Solanum bulbocastanum, has proven effective in greenhouse tests of transgenic cultivated potato. In this study, we examined the effects of the RB transgene on foliar late blight resistance in transgenic cultivated potato under field production conditions. In a two-year replicated trial, the RB transgene, under the control of its endogenous promoter, provided effective disease resistance in various genetic backgrounds, including commercially prominent potato cultivars, without fungicides. RB copy numbers and transcript levels were estimated with transgene-specific assays. Disease resistance was enhanced as copy numbers and transcript levels increased. The RB gene, like many other disease resistance genes, is constitutively transcribed at low levels. Transgenic potato lines with an estimated 15 copies of the RB transgene maintain high RB transcript levels and were ranked among the most resistant of 57 lines tested. We conclude that even in these ultra-high copy number lines, innate RNA silencing mechanisms have not been fully activated. Our findings suggest resistance-gene transcript levels may have to surpass a threshold before triggering RNA silencing. Strategies for the deployment of RB are discussed in light of the current research.

  11. Design, development and characterization of an x-band 5 bit DMTL phase shifter using an inline MEMS bridge and MAM capacitors

    NASA Astrophysics Data System (ADS)

    Dey, Sukomal; Koul, Shiban K.

    2014-09-01

    A radio frequency micro-electro-mechanical system (RF-MEMS) 5 bit phase shifter based on a distributed MEMS transmission line concept with excellent phase accuracy and good repeatability is presented in this paper. The phase shifter is built with three fixed-fixed beams; one is switchable with electrostatic actuation and the other two are fixed for a metal-air-metal (MAM) capacitor. The design is based on a coplanar waveguide (CPW) configuration using alumina substrate. Gold-based surface micromachining is used to develop the individual primary phase bits (11.25°/22.5°/45°/90°/180°), which are fundamental building blocks of the complete 5 bit phase shifter. All of the primary phase bits are cascaded together to build the complete phase shifter. Detailed design methodology and performance analysis of the unit cell phase shifter has been carried out with structural and parametric optimization using an in-line bridge and MAM capacitors. The mechanical, electrical, transient, intermodulation distortion (IMD), temperature distribution, power handling and loss performances of the MEMS bridge have been experimentally obtained and validated using simulations up to reasonable extent. A single unit cell is able to provide 31 dB return loss, maximum insertion loss of 0.085 dB and a differential phase shift of 5.95° (at 10 GHz) over the band of interest. Furthermore, all primary phase bits are individually tested to ensure overall optimum phase shifter performance. The complete 5 bit phase shifter demonstrates an average insertion loss of 4.72 dB with return loss of better than 12 dB within 8-12 GHz using periodic placement of 62 unit cells and a maximum phase error of ±3.2° has been obtained at 10 GHz. Finally, the x-band 5 bit phase shifter is compared with the present state-of-the-art. The performance of the 5 bit phase shifter when mounted inside a test jig has been experimentally investigated and the results are presented. The total area of

  12. Slow-Wave Phase Shifters, Based on Thin Ferroelectric Films, for Reflectarray Antennas. Frequency-Agile Radio: Systems and Technlogies, WMG 139

    NASA Technical Reports Server (NTRS)

    Romanofsky, Robert R.

    2006-01-01

    We have developed relatively broadband K- and Ka-band phase shifters using synthetic (slow-wave) transmission lines employing coupled microstripline "varactors". The tunable coupled microstripline circuits are based on laser ablated BaSrTiO films on lanthanum aluminate substrates. A model and design criteria for these novel circuits will be presented, along with measured performance including anomalous phase delay characteristics. The critical role of phase shifter loss and transient response in reflectarray antennas will be emphasized.

  13. Relationship between the Level of Acquired Resistance to Gentamicin and Synergism with Amoxicillin in Enterococcus faecalis

    PubMed Central

    Aslangul, Elisabeth; Ruimy, Raymond; Chau, Françoise; Garry, Louis; Andremont, Antoine; Fantin, Bruno

    2005-01-01

    In enterococci, intrinsic low-level resistance to gentamicin does not abolish synergism with a cell wall-active antibiotic while high-level resistance due to acquired aminoglycoside-modifying enzymes does. To study the impact of intermediate levels of resistance to gentamicin (64 < MIC < 500 μg/ml), we selected in vitro three consecutive generations of mutants of Enterococcus faecalis JH2-2 with MICs of gentamicin at 128 μg/ml for G1-1477, 256 μg/ml for G2-1573, and 512 μg/ml for G3-1688. E. faecalis 102, which is highly resistant to gentamicin by enzymatic inactivation was used as control. In in vitro killing curves experiments, gentamicin concentrations allowing bactericidal activity and synergism in combination with amoxicillin increased from 4 μg/ml (1/16th the MIC), 16 μg/ml (one-eighth the MIC), 64 μg/ml (one-quarter the MIC), and 256 μg/ml (one-half the MIC) for strains JH2-2, G1-1477, G2-1573 and G3-1688, respectively. As expected, no bactericidal effect of the combination or synergism could be obtained with strain 102. In rabbits with aortic endocarditis caused by strain G1-1477 or G2-1573, combination therapy with amoxicillin and gentamicin was significantly more active than amoxicillin alone (P < 0.05) but not in those infected with the strains G3-1688 and 102. Thus, intermediate levels of resistance to gentamicin was not associated with a loss of a beneficial effect of the gentamicin-amoxicillin combination in vivo even though higher concentrations of gentamicin were necessary to achieve in vitro synergism. Therefore, the use of an MIC of 500 μg/ml as a clinical cutoff limit to predict in vivo benefit of the combination remains a simple and effective tool. PMID:16189091

  14. Additional shear resistance from fault roughness and stress levels on geometrically complex faults

    NASA Astrophysics Data System (ADS)

    Fang, Zijun; Dunham, Eric M.

    2013-07-01

    The majority of crustal faults host earthquakes when the ratio of average background shear stress τb to effective normal stress σeff is τb/σeff≈0.6. In contrast, mature plate-boundary faults like the San Andreas Fault (SAF) operate at τb/σeff≈0.2. Dynamic weakening, the dramatic reduction in frictional resistance at coseismic slip velocities that is commonly observed in laboratory experiments, provides a leading explanation for low stress levels on mature faults. Strongly velocity-weakening friction laws permit rupture propagation on flat faults above a critical stress level τpulse/σeff≈0.25. Provided that dynamic weakening is not restricted to mature faults, the higher stress levels on most faults are puzzling. In this work, we present a self-consistent explanation for the relatively high stress levels on immature faults that is compatible with low coseismic frictional resistance, from dynamic weakening, for all faults. We appeal to differences in structural complexity with the premise that geometric irregularities introduce resistance to slip in addition to frictional resistance. This general idea is quantified for the special case of self-similar fractal roughness of the fault surface. Natural faults have roughness characterized by amplitude-to-wavelength ratios α between 10-3 and 10-2. Through a second-order boundary perturbation analysis of quasi-static frictionless sliding across a band-limited self-similar interface in an ideally elastic solid, we demonstrate that roughness induces an additional shear resistance to slip, or roughness drag, given by τdrag=8π3α2G∗Δ/λmin, for G∗=G/(1-ν) with shear modulus Gand Poisson's ratio ν, slip Δ, and minimum roughness wavelength λmin. The influence of roughness drag on fault mechanics is verified through an extensive set of dynamic rupture simulations of earthquakes on strongly rate-weakening fractal faults with elastic-plastic off-fault response. The simulations suggest that fault rupture, in

  15. Circulating Zinc-α2-glycoprotein levels and Insulin Resistance in Polycystic Ovary Syndrome

    PubMed Central

    Lai, Yerui; Chen, Jinhua; Li, Ling; Yin, Jingxia; He, Junying; Yang, Mengliu; Jia, Yanjun; Liu, Dongfang; Liu, Hua; Liao, Yong; Yang, Gangyi

    2016-01-01

    The aim of study was to assess the relationship between zinc-α2-glycoprotein (ZAG) and androgen excess with insulin resistance in polycystic ovary syndrome (PCOS) women. 99 PCOS women and 100 healthy controls were recruited. Euglycemic-hyperinsulinemic clamp (EHC) was preformed to assess their insulin sensitivity. Circulating ZAG was determined with an ELISA kit. In healthy subjects, circulating ZAG levels exhibited a characteristic diurnal rhythm in humans, with a major nocturnal rise occurring between midnight and early morning. Circulating ZAG and M-value were much lower in PCOS women than in the controls. In all population, overweight/obese subjects had significantly lower circulating ZAG levels than lean individuals. Multiple linear regression analysis revealed that only M-value and the area under the curve for glucose were independently related factors to circulating ZAG in PCOS women. Multivariate logistic regression analysis showed that circulating ZAG was significantly associated with PCOS even after controlling for anthropometric variables, blood pressure, lipid profile and hormone levels. The PCOS women with high ZAG had fewer MetS, IGT and polycystic ovaries as compared with the low ZAG PCOS women. Taken together, circulating ZAG levels are reduced in women with PCOS and ZAG may be a cytokine associated with insulin resistance in PCOS women. PMID:27180914

  16. Unraveling the genetic driving forces enabling antibiotic resistance at the single cell level

    NASA Astrophysics Data System (ADS)

    Bos, Julia

    Bacteria are champions at finding ways to quickly respond and adapt to environments like the human gut, known as the epicentre of antibiotic resistance. How do they do it? Combining molecular biology tools to microfluidic and fluorescence microscopy technologies, we monitor the behavior of bacteria at the single cell level in the presence of non-toxic doses of antibiotics. By tracking the chromosome dynamics of Escherichia coli cells upon antibiotic treatment, we examine the changes in the number, localization and content of the chromosome copies within one cell compartment or between adjacent cells. I will discuss how our work pictures the bacterial genomic plasticity as a driving force in evolution and how it provides access to the mechanisms controlling the subtle balance between genetic diversity and stability in the development of antibiotic resistance.

  17. Tunable and wideband microwave photonic phase shifter based on a single-sideband polarization modulator and a polarizer.

    PubMed

    Pan, Shilong; Zhang, Yamei

    2012-11-01

    A novel microwave photonic phase shifter based on a single-sideband (SSB) polarization modulator (PolM) and a polarizer is proposed and demonstrated. In the SSB-PolM, two SSB intensity-modulated signals with a phase difference of π along two orthogonal polarization directions are generated. With the polarizer to combine the two signals, the phase of the optical microwave signal can be tuned from -180 to 180 deg by simply adjusting the polarization direction of the polarizer, whereas the amplitude keeps unchanged. An experiment is carried out. A full-range tunable phase shift in the frequency range of 11-43 GHz is achieved. The flat power response, power independent operation, and high stability of the proposed microwave photonic phase shifter is also confirmed.

  18. Baseband integrated acousto-optic frequency shifter/modulator module for fiber optic at 1.3 mum.

    PubMed

    Tsai, C S; Cheng, Z Y

    1993-01-01

    A baseband integrated acoustooptic (AO) frequency shifter/modulator module that consists of a pair of titanium-indiffused proton-exchanged (TIPE) waveguide lenses and a pair of cascaded guided-wave AO Bragg cells has been realized in a Y-cut LiNbO(3) waveguide substrate 0.1 cmx1.0 cmx2.0 cm in size. A device module operating at the optical wavelength of 1.3 mum has provided a -3-dB tunable bandwidth of 120 MHz at baseband. The frequency-shifted or -modulated light propagates in a fixed direction, irrespective of the magnitude of frequency shift or modulation, and is focused into a spot (FWHM) of 6.2-mum size on the output edge of the waveguide. Accordingly, this optical frequency shifter/module can be directly interfaced with single-mode optical fibers to facilitate applications in fiber optic systems.

  19. Best approaches to drug-resistance surveillance at the country level.

    PubMed

    Cabibbe, A M; Cirillo, D M

    2016-12-01

    In 2014, the World Health Organization (WHO) recommendation to include the endorsed rapid molecular technologies (Xpert MTB/RIF, line probe assays) into surveillance systems and surveys allowed the testing of more tuberculosis (TB) patients for drug resistance at country level than ever before. The whole genome sequencing (WGS) approach is emerging as a more powerful tool for epidemiological and drug-resistant routine surveillances, promising a rapid and simultaneous screening of all the clinically-relevant mutations for the determination of resistance to the first-, second-line, and new anti-TB drugs. In addition, WGS can support the conventional contact tracing for epidemiological studies with high discriminatory power by tracking the circulating strains and their relatedness. These features make WGS, moreso than the conventional molecular tools, an ideal tool to monitor transmission and drug resistance trends in countries, providing deep and wide information in a standardized way. WGS technologies have already been adopted in many supranational and reference laboratories at the centralized level, and several research groups are working to reduce the complexity and costs of these platforms, from sample preparation to the downstream analysis and interpretation of sequencing reads, with the final aim to expand the use of WGS to all laboratory levels. The landscape of the platforms available for next-generation sequencing (NGS) is rapidly enriching. It includes high-throughput instruments that can be used for centralized surveillance studies on a large scale, and "benchtop" sequencers that conversely can reach more peripheral settings for rapid and non-extensive surveys. Traditionally, WGS is performed on genomic DNA samples extracted from clinical isolates to ensure the required high DNA quality and quantity for the following library preparation and sequencing reaction steps. Nevertheless, the researchers are trying to apply the WGS to early primary cultures and in

  20. Generation of Flat Optical Frequency Comb based on Mach-Zehnder Modulator and Recirculating Frequency Shifter Loop

    NASA Astrophysics Data System (ADS)

    Wu, Shibao; Li, Yulong; Fei, Yue; Hu, Faze

    2014-06-01

    We propose a novel scheme to generate optical frequency comb by using Mach-Zehnder modulator and recirculating frequency shifter loop based on IQ modulator driven by radio frequency clock signals. A system of 4 flat and stable comb lines generation based on Mach-Zehnder modulator is set as the seed light source of the recirculating loop. Through theorical analysis and simulation it is shown that the proposed theoretical model is proved in good agreement with simulation results.

  1. Zinc and homocysteine levels in polycystic ovarian syndrome patients with insulin resistance.

    PubMed

    Guler, Ismail; Himmetoglu, Ozdemir; Turp, Ahmet; Erdem, Ahmet; Erdem, Mehmet; Onan, M Anıl; Taskiran, Cagatay; Taslipinar, Mine Yavuz; Guner, Haldun

    2014-06-01

    In this study, our objective was to evaluating the value of serum zinc levels as an etiologic and prognostic marker in patients with polycystic ovarian syndrome. We conducted a prospective study, including 53 women with polycystic ovarian syndrome and 33 healthy controls. We compared serum zinc levels, as well as clinical and metabolic features, of the cases. We also compared serum zinc levels between patients with polycystic ovarian syndrome with insulin resistance. Mean zinc levels were found to be significantly lower in patients with polycystic ovarian syndrome than healthy controls. Multiple logistic regression analysis of significant metabolic variables between polycystic ovarian syndrome and control groups (serum zinc level, body mass index, the ratio of triglyceride/high-density lipoprotein cholesterol, and homocysteine) revealed that zinc level was the most significant variable to predict polycystic ovarian syndrome. Mean serum zinc levels tended to be lower in patients with polycystic ovarian syndrome with impaired glucose tolerance than patients with normal glucose tolerance, but the difference was not statistically significant. In conclusion, zinc deficiency may play a role in the pathogenesis of polycystic ovarian syndrome and may be related with its long-term metabolic complications.

  2. Studies of nitride- and oxide-based materials as absorptive shifters for embedded attenuated phase-shifting mask in 193 nm

    NASA Astrophysics Data System (ADS)

    Lin, Cheng-ming; Chang, Keh-wen; Lee, Ming-der; Loong, Wen-An

    1999-07-01

    Abstract-Five materials which are PdSixOy, CrAlxOy, SiNx, TiSixNy, and TiSixOyNz as absorptive shifters for attenuated phase-shifting mask in 193 nm wavelength lithography are presented. PdSixOy films were deposited by dual e-gun evaporation. CrAlxOy, TiSixNy and TiSixOyNz films were formed by plasma sputtering and SiNx films were formed with LPCVD. All of these materials are shown to be capable of achieving 4 percent - 15 percent transmittance in 193 nm with thickness that produce a 180 degrees phase shift. Under BCl3:Cl2 equals 14:70 sccm; chamber pressure 5 mtorr and RF power 1900W, the dry etching selectivity of TiSixNy over DQN positive resist and fused silica, were found to be 2:1 and 4,8:1 respectively. An embedded layer TiSixNy with 0.5 micrometers line/space was successfully patterned.

  3. Carotid-cardiac baroreflex influence on forearm vascular resistance during low level LBNP

    NASA Technical Reports Server (NTRS)

    Ludwig, David

    1990-01-01

    Twelve healthy males were tested at low levels of lower body negative pressure (LBNP) with and without artificial stimulation of the carotid-cardiac baroreceptors. The carotid-cardiac baroreceptors were stimulated by applying a pressure of 10 mmHg to the carotid artery via a pressurized neck chamber. During the procedure, forearm blood flow (FBF) and forearm vascular resistance (FVR) were measured using a Whitney mercury silastic strain gauge technique. FBF decreased while FVR increased with increased intensity of LBNP. Both FBF and FVR were unaffected by carotid-cardiac baroreceptor stimulation.

  4. Improvement of Leaching Resistance of Low-level Waste Form in Korea

    SciTech Connect

    Kim, J.Y.; Lee, B.C.; Kim, C.L.

    2006-07-01

    Low-level liquid concentrate wastes including boric acid have been immobilized with paraffin wax using concentrate waste drying system in Korean nuclear power plants since 1995. Small amount of low density polyethylene (LDPE) was added to increase the leaching resistance of the existing paraffin waste form and the influence of LDPE on the leaching behavior of waste form was investigated. It was observed that the leaching of nuclides immobilized within paraffin waste form remarkably reduced as the content of LDPE increased. The acceptance criteria of paraffin waste form associated with leachability index and compressive strength after the leaching test were successfully satisfied with the help of LDPE. (authors)

  5. Low-level resistance and clonal diversity of Pseudomonas aeruginosa among chronically colonized cystic fibrosis patients.

    PubMed

    Ferreira, Alex Guerra; Leão, Robson Souza; Carvalho-Assef, Ana Paula D'alincourt; da Silva, Érica Aparecida dos Santos Ribeiro; Firmida, Monica de Cássia; Folescu, Tania Wrobel; Paixão, Vilma Almeida; Santana, Maria Angélica; de Abreu e Silva, Fernando Antonio; Barth, Afonso Luís; Marques, Elizabeth Andrade

    2015-12-01

    A prospective study was conducted in Brazil to evaluate antimicrobial resistance patterns and molecular epidemiology of Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients with chronic lung infection. All isolates were obtained between May 2009 and June 2010 from 75 patients seen in four reference centers in Brazil: HCPA (20 patients) and HEOM (15 patients), located in southern and northeastern Brazil, respectively; IFF (20 patients) and HUPE (20 patients), both in southwestern Brazil. Antimicrobial susceptibility testing, PCR for detection of carpapenemases, and pulsed-field gel electrophoresis (PFGE) were performed in 274 isolates. A total of 224 PFGE types were identified and no clones were found circulating among the centers or within the same center. Despite the chronic infection, most patients were colonized by intermittent clones. Only three patients (4%) maintained the same clone during the study. The resistance rates were lower than 30% for the majority of antimicrobials tested in all centers and only 17% of isolates were multiresistant. Isolates (n = 54) with reduced susceptibility to imipenem and/or meropenem presented negative results for blaSPM-1, blaIMP-1, blaVIM , and blaKPC genes. Our results indicate an unexpected low level of antimicrobial resistance and a high genotypic diversity among P. aeruginosa from Brazilian chronic CF patients.

  6. Fall armyworm and corn earworm resistance in the breeding crosses of maize inbreds with high levels of phytoalexins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In order to develop maize germplasm with resistance to multiple insect pests and aflatoxin accumulation, a set of reciprocal breeding crosses was made using maize inbred lines with high levels of kauralexins or zealexins. The evaluation of the breeding crosses for insect resistance utilized the rand...

  7. Adiponectin serum levels correlate with insulin resistance in type 2 diabetic patients

    PubMed Central

    Aleidi, Shereen; Issa, Ala; Bustanji, Haidar; Khalil, Mohammad; Bustanji, Yasser

    2014-01-01

    The adipose tissue is not only an inert storage depot for lipids, but also it secretes a variety of bioactive molecules, known as adipokines, which affect whole-body homeostasis. Adiponectin is the most abundant of these adipocytokines and is known to have a regulatory effect on the metabolism of glucose and lipid. The main objectives of this study were to evaluate the serum levels of adiponectin and to establish a correlation between adiponectin serum levels and the degree of insulin resistance in type 2 diabetic patients. Eighty participants were enrolled in this study; 61 type 2 diabetic patients and 19 apparently healthy subjects. Serum level of adiponectin was measured by enzyme-linked immunosorbent assay (ELISA) for each participant. Data collection sheet was filled with all required information for each participant. Adiponectin level in the diabetic patients (5.05 ± 2.61 μg/ml) was lower than in non-diabetic healthy controls (5.71 ± 2.35 μg/ml). When the results were compared according to gender, diabetic females showed significantly higher adiponectin levels (5.76 ± 2.64 μg/ml) than diabetic males (4.366 ± 2.43 μg/ml, P = 0.035). In addition, female diabetic patients with abdominal obesity (waist circumference (WC) ⩾ 88 cm) had lower adiponectin levels (5.58 ± 2.58 μg/ml) than diabetic females without abdominal obesity (6.96 ± 3.12 μg/ml). The correlation analysis indicated that adiponectin had a significant positive correlation with age (r = −0.450, P < 0.001). In conclusion, female diabetic patients had a statistically significant higher adiponectin level than male diabetic patients which could indicate a gender effect. Adiponectin levels were inversely related to insulin resistance; as patients with abdominal obesity had lower serum levels of adiponectin. PMID:26106273

  8. Decreased Level of Klotho Contributes to Drug Resistance in Lung Cancer Cells: Involving in Klotho-Mediated Cell Autophagy.

    PubMed

    Chen, TianJun; Ren, Hui; Thakur, Asmitanand; Yang, Tian; Li, Yang; Zhang, Shuo; Wang, Ting; Chen, MingWei

    2016-12-01

    Klotho is originally discovered as an anti-aging gene and recently identified as a tumor suppressor in various human cancers. Drug resistance is a major obstacle to affect the treatment of chemotherapy. In the present study, we explore the role of klotho on drug resistance in human lung cancers and investigate the mechanism of klotho on drug resistance in lung cancer cells. First, we detected a panel of six human lung cancer cell lines, including H460, SK-MES-1, cisplatin (DDP)-resistant A549/DDP, its parental subline A549, docetaxel (DTX)-resistant SPC-A-1/DTX, and SPC-A-1 by western blotting analysis. The results showed that klotho level was significantly decreased in chemotherapeutic drug-resistant lung cancer cells. Next, klotho was overexpressed in drug-resistant cancer cell lines and the results showed that overexpression of klotho significantly inhibited cell proliferation of A549/DDP and SPC-A-1/DTX. Conversely, knockdown of the expression of klotho significantly promoted cell growth of lung cancer cells. Furthermore, overexpression of klotho had synergistic effects with cisplatin to inhibit the proliferation of drug-resistant lung cancer cells in a dose- and time-dependent manner. The molecular mechanism was explored by western blotting analysis and the results revealed that the levels of beclin 1 and LC3-II were obviously increased, suggesting cell autophagy enhanced in drug-resistant cancer cells. Importantly, overexpression of klotho would inhibit cell autophagy in A549/DDP cells. All the results demonstrated that the levels of klotho were significantly decreased, which was accompanied by the increased cell autophagy in drug-resistant lung cancer cells. Overexpression of klotho would inhibit cell autophagy in drug-resistant lung cancers, which may probably contribute to reverse drug resistance in lung cancer cells.

  9. A Small Amount of Dietary Carbohydrate Can Promote the HFD-Induced Insulin Resistance to a Maximal Level

    PubMed Central

    Guo, Huailan; Gu, Haihua; Zha, Longying; Cai, Junwei; Li, Xuefeng; Liu, Zhenqi; Bennett, Brian J.; He, Ling; Cao, Wenhong

    2014-01-01

    Both dietary fat and carbohydrates (Carbs) may play important roles in the development of insulin resistance. The main goal of this study was to further define the roles for fat and dietary carbs in insulin resistance. C57BL/6 mice were fed normal chow diet (CD) or HFD containing 0.1–25.5% carbs for 5 weeks, followed by evaluations of calorie consumption, body weight and fat gains, insulin sensitivity, intratissue insulin signaling, ectopic fat, and oxidative stress in liver and skeletal muscle. The role of hepatic gluconeogenesis in the HFD-induced insulin resistance was determined in mice. The role of fat in insulin resistance was also examined in cultured cells. HFD with little carbs (0.1%) induced severe insulin resistance. Addition of 5% carbs to HFD dramatically elevated insulin resistance and 10% carbs in HFD was sufficient to induce a maximal level of insulin resistance. HFD with little carbs induced ectopic fat accumulation and oxidative stress in liver and skeletal muscle and addition of carbs to HFD dramatically enhanced ectopic fat and oxidative stress. HFD increased hepatic expression of key gluconeogenic genes and the increase was most dramatic by HFD with little carbs, and inhibition of hepatic gluconeogenesis prevented the HFD-induced insulin resistance. In cultured cells, development of insulin resistance induced by a pathological level of insulin was prevented in the absence of fat. Together, fat is essential for development of insulin resistance and dietary carb is not necessary for HFD-induced insulin resistance due to the presence of hepatic gluconeogenesis but a very small amount of it can promote HFD-induced insulin resistance to a maximal level. PMID:25055153

  10. Resistance Level of Mosquito Species (Diptera: Culicidae) from Shandong Province, China.

    PubMed

    Liu, Hong-Mei; Yang, Pei-Pei; Cheng, Peng; Wang, Hai-Fang; Liu, Li-Juan; Huang, Xiaodan; Zhao, Yu-Qiang; Wang, Huai-Wei; Zhang, Chong-Xing; Gong, Mao-Qing

    2015-01-01

    This study describes the aquatic habitats, species composition, and the insecticide resistance level of the mosquito Culex pipiens pallens in Shandong Province, China. A cross-sectional survey of mosquito larval habitats was conducted from May to November 2014 to determine the species composition and larval abundance. Larvae were collected using the standard dipping technique, and a total of four habitat types were sampled. The fourth instar larvae of Cx. pipiens pallens collected in each habitat type were tested for resistance to five insecticides according to a WHO bioassay. A total of 7,281 mosquito larvae were collected, of which 399 (5.48%) were categorized as Anopheles mosquito larvae (An. sinensis), 6636 (91.14%) as culicine larvae (Cx. pipiens pallens, Cx. tritaeniorhynchus, Cx. halifaxii, and Cx. bitaeniorhynchus), 213 (2.93%) as Armigeres larvae, and 33 (0.45%) as Aedes larvae (Aedes albopictus). In addition, a total of 1,149 mosquito pupae were collected. Culex larvae were distributed in all habitats investigated. Tukeys HSD analysis showed that roadside drainages were the most productive habitat type for Culex larvae. Armigeres species were found only in drains, Aedes only in water tanks, and Anopheles in water that was comparatively clear and rich in emergent plants. Bioassay showed that the maximum resistance level of Cx. pipiens pallens was to deltamethrin, while it was lowest to plifenate. The productivity of various mosquitoes in different habitat types is very heterogeneous. It is particularly important to modify human activity and the environment to achieve effective mosquito vector control. For effective larval control, the type of habitat should be considered, and the most productive habitat type should be given priority in mosquito abatement programs.

  11. Resistance Training in Type 2 Diabetic Patients Improves Uric Acid levels

    PubMed Central

    Sousa, Moisés S.S.R.; Saavedra, Francisco J.F.; Neto, Gabriel R.; Novaes, Giovanni S.; Souza, Antonio C. R.; Salerno, Verônica P.; Novaes, Jefferson S.

    2014-01-01

    Resistance training (RT) can provide several benefits for individuals with Type 2 diabetes. The aim of this study was to investigate the effects of resistance training on the strength levels and uric acid (UA) concentration in individuals with Type 2 diabetes. The study included 68 patients (57.7±9.0 years) that participated in an organized program of RT for 12 weeks. The volunteers were divided into two groups: an experimental group (EG; n=34) that performed the resistance training program consisting of seven exercises executed in an alternating order based on segments; and a control group (CG; n=34) that maintained their normal daily life activities. Muscle strength and uric acid were measured both pre- and post-experiment. The results showed a significant increase in strength of the subjects in the EG for all exercises included in the study (p<0.001). Comparing the strength levels of the post-test, intergroup differences were found in supine sitting (p<0.001), leg extension (p<0.001), shoulder press (p<0.001), leg curl (p=0.001), seated row (p<0.001), leg press (p=0.001) and high pulley (p<0.001). The measured uric acid was significantly increased in both experimental and control groups (p<0.001 and p=0.001, respectively). The intergroup comparison showed a significant increase for the EG (p=0.024). We conclude that the training program was effective for strength gains despite an increase in uric acid in Type 2 diabetics. PMID:25713640

  12. Resistance Level of Mosquito Species (Diptera: Culicidae) from Shandong Province, China

    PubMed Central

    Liu, Hong-Mei; Yang, Pei-Pei; Cheng, Peng; Wang, Hai-Fang; Liu, Li-Juan; Huang, Xiaodan; Zhao, Yu-Qiang; Wang, Huai-Wei; Zhang, Chong-Xing; Gong, Mao-Qing

    2015-01-01

    This study describes the aquatic habitats, species composition, and the insecticide resistance level of the mosquito Culex pipiens pallens in Shandong Province, China. A cross-sectional survey of mosquito larval habitats was conducted from May to November 2014 to determine the species composition and larval abundance. Larvae were collected using the standard dipping technique, and a total of four habitat types were sampled. The fourth instar larvae of Cx. pipiens pallens collected in each habitat type were tested for resistance to five insecticides according to a WHO bioassay. A total of 7,281 mosquito larvae were collected, of which 399 (5.48%) were categorized as Anopheles mosquito larvae (An. sinensis), 6636 (91.14%) as culicine larvae (Cx. pipiens pallens, Cx. tritaeniorhynchus, Cx. halifaxii, and Cx. bitaeniorhynchus), 213 (2.93%) as Armigeres larvae, and 33 (0.45%) as Aedes larvae (Aedes albopictus). In addition, a total of 1,149 mosquito pupae were collected. Culex larvae were distributed in all habitats investigated. Tukeys HSD analysis showed that roadside drainages were the most productive habitat type for Culex larvae. Armigeres species were found only in drains, Aedes only in water tanks, and Anopheles in water that was comparatively clear and rich in emergent plants. Bioassay showed that the maximum resistance level of Cx. pipiens pallens was to deltamethrin, while it was lowest to plifenate. The productivity of various mosquitoes in different habitat types is very heterogeneous. It is particularly important to modify human activity and the environment to achieve effective mosquito vector control. For effective larval control, the type of habitat should be considered, and the most productive habitat type should be given priority in mosquito abatement programs. PMID:26816489

  13. Isoflavone, glyphosate, and aminomethylphosphonic acid levels in seeds of glyphosate-treated, glyphosate-resistant soybean.

    PubMed

    Duke, Stephen O; Rimando, Agnes M; Pace, Patrick F; Reddy, Krishna N; Smeda, Reid J

    2003-01-01

    The estrogenic isoflavones of soybeans and their glycosides are products of the shikimate pathway, the target pathway of glyphosate. This study tested the hypothesis that nonphytotoxic levels of glyphosate and other herbicides known to affect phenolic compound biosynthesis might influence levels of these nutraceutical compounds in glyphosate-resistant soybeans. The effects of glyphosate and other herbicides were determined on estrogenic isoflavones and shikimate in glyphosate-resistant soybeans from identical experiments conducted on different cultivars in Mississippi and Missouri. Four commonly used herbicide treatments were compared to a hand-weeded control. The herbicide treatments were (1) glyphosate at 1260 g/ha at 3 weeks after planting (WAP), followed by glyphosate at 840 g/ha at 6 WAP; (2) sulfentrazone at 168 g/ha plus chlorimuron at 34 g/ha applied preemergence (PRE), followed by glyphosate at 1260 g/ha at 6 WAP; (3) sulfentrazone at 168 g/ha plus chlorimuron at 34 g/ha applied PRE, followed by glyphosate at 1260 g/ha at full bloom; and (4) sulfentrazone at 168 g/ha plus chlorimuron at 34 g/ha applied PRE, followed by acifluorfen at 280 g/ha plus bentazon at 560 g/ha plus clethodim at 140 g/ha at 6 WAP. Soybeans were harvested at maturity, and seeds were analyzed for daidzein, daidzin, genistein, genistin, glycitin, glycitein, shikimate, glyphosate, and the glyphosate degradation product, aminomethylphosphonic acid (AMPA). There were no remarkable effects of any treatment on the contents of any of the biosynthetic compounds in soybean seed from either test site, indicating that early and later season applications of glyphosate have no effects on phytoestrogen levels in glyphosate-resistant soybeans. Glyphosate and AMPA residues were higher in seeds from treatment 3 than from the other two treatments in which glyphosate was used earlier. Intermediate levels were found in treatments 1 and 2. Low levels of glyphosate and AMPA were found in treatment 4 and a

  14. Performance of UV-glass MaPMT with p-Terphenyl Wavelength Shifter

    NASA Astrophysics Data System (ADS)

    Rehfuss, Melanie; Joosten, Sylvester; Meziani, Zein-Eddine; Kaczanowicz, Edward

    2016-03-01

    UV-glass PMTs are often the limiting factor in a Cherenkov detector because of their poor quantum efficiency (QE) below 300nm due to the UV-glass transparency. The application of a p-Terphenyl wavelength shifter to the face of these PMTs dramatically improves the QE for short wavelengths, rivaling that of a much more expensive quartz PMT. This is especially interesting in the context of multi-anode (Ma) PMTs, which are supremely suited for application in future open-environment Cherenkov detectors at very high luminosities due to their small size, lower sensitivity to magnetic fields, and high potential for advanced background rejection due to their pixelization. This will become critical at Jefferson Lab entering the 12 GeV era, as well as for a future electron-ion collider both providing a high luminosity. We will discuss the process of coating the PMTs through vacuum evaporation, and the performance testing taking place at Temple University for Hamamatsu model H12700A-03 multi-anode PMTs as well the background rejection schemes that will be devised using these MaPMTs.

  15. Improving UV-glass PMTs with a p-Terphenyl Wavelength Shifter

    NASA Astrophysics Data System (ADS)

    Joosten, Sylvester; Meziani, Zein-Eddine; Kaczanowicz, Ed; Rehfuss, Melanie; Duran, Burcu; Paolone, Michael

    2015-10-01

    UV-glass PMTs are often the limiting factor in a Cherenkov detector, due to their poor quantum efficiency (QE) below 300nm due to the UV-glass transparency. The application of a p-Terphenyl wavelength shifter to the face of these PMTs dramatically improves the QE for short wavelengths, rivaling that of a much more expensive quartz PMT. This is especially interesting in the context of multi-anode (MA) PMTs, which are supremely suited for application in future open-environment Cherenkov detectors at very high luminosities due to their small size, lower sensitivity to magnetic fields, and high potential for advanced background rejection. This will become critical at Jefferson Lab entering the 12 GeV era, as well as for a future electron-ion collider. We will discuss the process of coating the PMTs through vacuum evaporation, and the performance testing taking place at Temple University for these multi-anode PMTs, as well as the results obtained with the more traditional 5-inch PMTs that were coated for the low-threshold Cherenkov counter (LTCC) of the CLAS12 spectrometer at Jefferson Lab.

  16. Non-mechanical sub-pixel image shifter for acquiring super-resolution digital images.

    PubMed

    Lan, Hsiao-Chin; Wu, Mount-Learn; Yeatman, Eric M

    2009-12-07

    A sub-pixel image shifter is presented, for use in enhancing the spatial resolution of digital image sensors by combining multiple displaced sub-images using a super-resolution (SR) algorithm. The device uses the walk-off phenomenon in birefringent crystals to separate images with opposite polarizations by a sub-pixel displacement. A liquid crystal (LC) waveplate plus a polarizer can then select the specific image to be exposed, with fast, non-mechanical control. This cascaded device, comprising two sapphire crystals, two LCs, and a single polarizer, is capable of 2-dimensional image shift with displacements of 0.5 pixels. The experimental results show that the image registration stability can be precisely controlled within 0.05 pixels and the contrast transfer function ratio of the SR image is enhanced by up to 1.36 times compared to the original captured image. Moreover, based on the fast transition time of LCs, the displaced sub-images can be recorded in video form with a frame rate of 40 fps.

  17. Thin-Film Ferro Electric-Coupled Microstripline Phase Shifters With Reduced Device Hysteresis

    NASA Technical Reports Server (NTRS)

    Miranda, Felix A.; Romanofsky, Robert; Mueller, Carl H.; VanKeuls, Frederick

    2010-01-01

    This work deals with the performance of coupled microstripline phase shifters (CMPS) fabricated using BaxSr 1 -xTiO 3 (BST) ferroelectric thin films. The CMPS were fabricated using commercially available pulsed laser deposition BST films with Ba:Sr ratios of 30:70 and 20:80. Microwave characterization of these CMPS was performed at upper Kuband frequencies, particularly at frequencies near 16 and 18 GHz. X-ray diffraction studies indicate that the 30:70 films exhibit almost a 1:1 ratio between the in-plane and out-of-plane lattice parameters, suggesting that their cubics create strain -free films suitable for producing CMPS devices with reduced hysteresis in the paraelectric state. The quality of performance of the CMPS was studied based on their relative phase shift and insertion loss within the DC bias range of 0 to 400 V (i.e., E-field ranges within 0 to 53 V/micron). The performance of the CMPS was tested as a function of temperature to investigate their operation in the paraelectric, as well as in the ferroelectric, state (i.e., above and below the Curie temperature, respectively). The novel behavior discussed here is based on the experimental observation of the CMPS. This behavior, observed for the aforementioned cation ratio, highlights the relevance of good crystalline structure for high-quality CMPS.

  18. Pulsed ultra-cold neutron production using a Doppler shifter at J-PARC

    NASA Astrophysics Data System (ADS)

    Imajo, S.; Mishima, K.; Kitaguchi, M.; Iwashia, Y.; Yamada, N. L.; Hino, M.; Oda, T.; Ino, T.; Shimizu, H. M.; Yamashita, S.; Katayama, R.

    2016-01-01

    We have constructed a Doppler-shifter-type pulsed ultra-cold neutron (UCN) source at the Materials and Life Science Experiment Facility of the Japan Proton Accelerator Research Complex. Very cold neutrons (VCNs) with 136 m s^{-1} velocity in a neutron beam supplied by a pulsed neutron source are decelerated by reflection on an m=10 wide-band multilayer mirror, yielding pulsed UCNs. The mirror is fixed to the tip of a 2000 rpm rotating arm moving with 68 m s^{-1} velocity in the same direction as the VCNs. The repetition frequency of the pulsed UCNs is 8.33 Hz and the time width of the pulse at production is 4.4 ms. In order to increase the UCN flux, a supermirror guide, wide-band monochromatic mirrors, focus guides, and a UCN extraction guide have been newly installed or improved. The 1 MW-equivalent count rate of the output neutrons with longitudinal wavelengths longer than 58 nm is 1.6 × 102 cps, while that of the true UCNs is 80 cps. The spatial density at production is 1.4 UCN cm^{-3}. This new UCN source enables us to research and develop apparatuses necessary for the investigation of the neutron electric dipole moment.

  19. Possibilities of achromatization of coaxial asymmetric phase shifters with an even number of reflections

    NASA Astrophysics Data System (ADS)

    Kovalev, V. I.; Ali, M.; Kovalev, S. V.; Kovalev, V. V.

    2014-07-01

    Two types of coaxial phase shifters (PSs) are considered. They are designed for spectral ellipsometry, where achromatism is improved using a pair of parallel Al mirrors oriented at small angle θ2 with respect to the incident laser beam. In a phase device based on a fused silica Fresnel rhomb, a high degree of achromatism (Δ = 440° ± 0.4° in the wavelength range of 250-1000 nm) is obtained with the aid of two Al mirrors coated by a native oxide layer about 5 nm thick and tilted at θ2 = 18°. The achromatism of four-mirror PSs can be improved using two mirrors with a thin dielectric coating (Al2O3 or MgF2) 20-80 nm thick, for which phase shift Δ is close to 180° at small angles θ2 and there are fragments of spectrum Δ(λ) where Δ decreases with an increase in the light wavelength.

  20. In vitro antibacterial activity of seven Indian spices against high level gentamicin resistant strains of enterococci

    PubMed Central

    Bipin, Chapagain; Chitra, Pai (Bhat); Minakshi, Bhattacharjee

    2015-01-01

    Introduction The aim of the study was to explore the in vitro antibacterial activity of seven ethanolic extracts of spices against high level gentamicin resistant (HLGR) enterococci isolated from human clinical samples. Material and methods Two hundred and fifteen enterococcal strains were isolated from clinical samples. High level gentamicin resistance in ethanolic extracts of cumin (Cuminum cyminum), cinnamon (Cinnamomum zeylanicum), ginger (Zingiber officinale), fenugreek (Trigonella foenum-graecum), cloves (Syzygium aromaticum), cardamom (Elettaria cardamomum Maton) and black pepper (Piper nigrum) were prepared using Soxhlet apparatus. The antibacterial effect of the extracts was studied using the well diffusion method. Statistical analysis was carried out by χ2 test using SPSS 17 software. Results Only cinnamon and ginger were found to have activity against all the isolates, whereas cumin and cloves had a variable effect on the strains. Fenugreek, black pepper and cardamom did not show any effect on the isolates. The zone diameter of inhibition obtained for cinnamon, ginger, cloves and cumin was in the range 31–34 mm, 27–30 mm, 25–26 mm and 19–20 mm respectively. Conclusions Cinnamomum zeylanicum and Z. officinale showed the maximum antibacterial activity against the enterococcal isolates followed by S. aromaticum and C. cyminum. The findings of the study show that spices used in the study can contribute to the development of potential antimicrobial agents for inclusion in the anti-enterococcal treatment regimen. PMID:26322099

  1. Relationships between changes in leptin and insulin resistance levels in obese individuals following weight loss.

    PubMed

    Wang, Tsu-Nai; Chang, Wen-Tsan; Chiu, Yu-Wen; Lee, Chun-Ying; Lin, Kun-Der; Cheng, Yu Yao; Su, Yi-Ju; Chung, Hsin-Fang; Huang, Meng-Chuan

    2013-08-01

    Obesity can augment insulin resistance (IR), leading to increased risk of diabetes and heart disease. Leptin, ghrelin, and various fatty acids present in the cell membrane may modulate IR. In this study, we aimed to investigate the impact of weight loss on IR, serum leptin/ghrelin levels, and erythrocyte fatty acids, and studied the associations between changes in these variables. A total of 35 obese (body mass index ≥ 27) adults participated in a weight loss program for 3 months. IR was assessed using homeostasis model assessment for insulin resistance (HOMA-IR). The obese participants had a mean weight loss of 5.6 ± 3.8 kg followed by a 16.7% and 23.3% reduction in HOMA-IR and leptin (p < 0.001) levels, and an 11.3% increase in ghrelin levels (p = 0.005). The level of erythrocyte saturates decreased by 2.8%, while the level of n-3 polyunsaturates increased by 16.8% (all p < 0.05). The changes in leptin levels (-5.63 vs. -1.57 ng/mL) were significantly different (p = 0.004) in those with improved IR (changes in HOMA-IR < 0) than those without improvement (changes in HOMA-IR ≥ 0), though there were no differences in the changes of ghrelin (p = 0.120) and erythrocyte fatty acids (all p > 0.05) levels. After adjusting for age, gender, changes in ghrelin, and body fat, we found a significant correlation between decreases in leptin and less risk of no improvement in HOMA-IR levels [odds ratio (OR) = 0.69, p = 0.039]. In conclusion, a moderate weight reduction in obese participants over a short period significantly improved IR. This weight reduction concomitantly decreased serum leptin, increased ghrelin, and elevated some erythrocyte unsaturates. Only leptin correlated independently with IR improvement upon multivariable logistic regression analysis, which indicates that leptin may play a role in the modulation of IR following weight loss.

  2. Geometric Morphometrics of Nine Field Isolates of Aedes aegypti with Different Resistance Levels to Lambda-Cyhalothrin and Relative Fitness of One Artificially Selected for Resistance

    PubMed Central

    Jaramillo-O., Nicolás; Fonseca-González, Idalyd; Chaverra-Rodríguez, Duverney

    2014-01-01

    Aedes aegypti, a mosquito closely associated with humans, is the principal vector of dengue virus which currently infects about 400 million people worldwide. Because there is no way to prevent infection, public health policies focus on vector control; but insecticide-resistance threatens them. However, most insecticide-resistant mosquito populations exhibit fitness costs in absence of insecticides, although these costs vary. Research on components of fitness that vary with insecticide-resistance can help to develop policies for effective integrated management and control. We investigated the relationships in wing size, wing shape, and natural resistance levels to lambda-cyhalothrin of nine field isolates. Also we chose one of these isolates to select in lab for resistance to the insecticide. The main life-traits parameters were assessed to investigate the possible fitness cost and its association with wing size and shape. We found that wing shape, more than wing size, was strongly correlated with resistance levels to lambda-cyhalothrin in field isolates, but founder effects of culture in the laboratory seem to change wing shape (and also wing size) more easily than artificial selection for resistance to that insecticide. Moreover, significant fitness costs were observed in response to insecticide-resistance as proved by the diminished fecundity and survival of females in the selected line and the reversion to susceptibility in 20 generations of the non-selected line. As a practical consequence, we think, mosquito control programs could benefit from this knowledge in implementing efficient strategies to prevent the evolution of resistance. In particular, the knowledge of reversion to susceptibility is important because it can help in planning better strategies of insecticide use to keep useful the few insecticide-molecules currently available. PMID:24801598

  3. Geometric morphometrics of nine field isolates of Aedes aegypti with different resistance levels to lambda-cyhalothrin and relative fitness of one artificially selected for resistance.

    PubMed

    Jaramillo-O, Nicolás; Fonseca-González, Idalyd; Chaverra-Rodríguez, Duverney

    2014-01-01

    Aedes aegypti, a mosquito closely associated with humans, is the principal vector of dengue virus which currently infects about 400 million people worldwide. Because there is no way to prevent infection, public health policies focus on vector control; but insecticide-resistance threatens them. However, most insecticide-resistant mosquito populations exhibit fitness costs in absence of insecticides, although these costs vary. Research on components of fitness that vary with insecticide-resistance can help to develop policies for effective integrated management and control. We investigated the relationships in wing size, wing shape, and natural resistance levels to lambda-cyhalothrin of nine field isolates. Also we chose one of these isolates to select in lab for resistance to the insecticide. The main life-traits parameters were assessed to investigate the possible fitness cost and its association with wing size and shape. We found that wing shape, more than wing size, was strongly correlated with resistance levels to lambda-cyhalothrin in field isolates, but founder effects of culture in the laboratory seem to change wing shape (and also wing size) more easily than artificial selection for resistance to that insecticide. Moreover, significant fitness costs were observed in response to insecticide-resistance as proved by the diminished fecundity and survival of females in the selected line and the reversion to susceptibility in 20 generations of the non-selected line. As a practical consequence, we think, mosquito control programs could benefit from this knowledge in implementing efficient strategies to prevent the evolution of resistance. In particular, the knowledge of reversion to susceptibility is important because it can help in planning better strategies of insecticide use to keep useful the few insecticide-molecules currently available.

  4. Homocysteine levels in morbidly obese patients: its association with waist circumference and insulin resistance.

    PubMed

    Vayá, Amparo; Rivera, Leonor; Hernández-Mijares, Antonio; de la Fuente, Miguel; Solá, Eva; Romagnoli, Marco; Alis, R; Laiz, Begoña

    2012-01-01

    The association between morbid obesity and hyperhomocysteinemia (HH) remains controversial and the nature of this relationship needs to be clarified as several metabolic, lipidic, inflammatory and anthropometric alterations that accompany morbid obesity may be involved. In 66 morbidly obese patients, 47 women and 19 men aged 41 ± 12 years and 66 normo-weight subjects, 43 women and 23 men, aged 45 ± 11 years, we determined homocysteine (Hcy) levels along with lipidic, anthropometric, inflammatory and insulin resistance markers. In addition, we investigated the effect of Metabolic Syndrome (MS) and its components on Hcy levels. Obese patients had statistically higher Hcy levels than controls: 12.76 ± 5.30 μM vs. 10.67 ± 2.50 μM; p = 0.006. Moreover, morbidly obese subjects showed higher waist circumference, glucose, insulin, HOMA, leptin, triglycerides, fibrinogen, C reactive protein (CRP) (p < 0.001, respectively), and lower vitamin B12 (p = 0.002), folic acid and HDL-cholesterol (p < 0.001, respectively). In the multivariate regression analysis, waist circumference, glucose, leptin and folic acid levels were independent predictors for Hcy values (p < 0.050). When obese patients were classified as having MS or not, no differences in Hcy levels were found between the two groups (p = 0.752). Yet when we analysed separately each MS component, only abdominal obesity was associated with Hcy levels (p = 0.031). Moreover when considering glucose >110 mg/dL (NCEP-ATPIII criteria) instead of glucose intolerance >100 mg/dl (updated ATPIII criteria), it also was associated with HH (p = 0.042). These results were confirmed in the logistic regression analysis where abdominal obesity and glucose >115 mg/dL constitute independent predictors for HH (OR = 3.2; CI: 1.23-13.2; p = 0.032, OR: 4.6; CI: 1.7-22.2; p = 0.016, respectively). The results of our study indicate that increased Hcy levels are related mostly with abdominal obesity and with insulin resistance. Thus, HH may

  5. Resistance Responses of Potato to Vesicular-Arbuscular Mycorrhizal Fungi under Varying Abiotic Phosphorus Levels.

    PubMed

    McArthur, D A; Knowles, N R

    1992-09-01

    to plant growth decreased and root infection was lower. The in vivo ACC(ox) activity was also greater in roots of plants grown on high levels of P compared with those grown on low levels, although the influence of VAM infection was partially to counteract the nutritional effect of P on ACC(ox) activity. Similar to ACC(ox) activity, extracellular peroxidase activity of roots increased linearly with increasing abiotic P supply, thus indicating a greater potential for resistance to VAM infection. These findings suggest that VAM fungi may alter phenolic metabolism of roots so as to hinder ethylene production and the root's ability to invoke a defense response. Raising the abiotic P supply to plants at least partially restores the capacity of roots to produce ethylene and may, in this way, increase the root's resistance to VAM infection.

  6. Effects of soybean resistance on variability in life history traits of the higher trophic level parasitoid Meteorus pulchricornis (Hymenoptera: Braconidae).

    PubMed

    Li, X; Li, B; Xing, G; Meng, L

    2017-02-01

    To extrapolate the influence of plant cultivars varying in resistance levels to hosts on parasitoid life history traits, we estimated variation in parasitoid developmental and reproductive performances as a function of resistance in soybean cultivars, which were randomly chosen from a line of resistant genotypes. Our study showed that the parasitoid Meteorus pulchricornis varied widely in offspring survival and lifetime fecundity, but varied slightly in development time and adult body size, in response to the soybean cultivars that varied in resistance to the host Spodoptera litura. Furthermore, the variability in survival and lifetime fecundity was different between attacking the 2nd and the 4th instar host larvae, varying more in survival but less in lifetime fecundity when attacking the 4th than 2nd instar larvae. Our study provides further evidence supporting that plant resistance to herbivorous hosts have variable effects on different life history traits of higher trophic level parasitoids.

  7. Universal high-level primary metronidazole resistance in Helicobacter pylori isolated from children in Egypt.

    PubMed

    Sherif, May; Mohran, Zaynab; Fathy, Hanan; Rockabrand, David M; Rozmajzl, Patrick J; Frenck, Robert W

    2004-10-01

    Antimicrobial susceptibility testing was performed on 48 isolates of Helicobacter pylori recovered from Egyptian children undergoing routine endoscopies. The isolates were universally highly resistant to metronidazole, but resistance to other tested antimicrobial agents was rare (4% for clarithromycin, erythromycin, and azithromycin resistance versus 2% for ciprofloxacin and ampicillin resistance). Use of metronidazole for the treatment of H. pylori in Egypt should be avoided.

  8. Insulin resistance and normal thyroid hormone levels: prospective study and metabolomic analysis.

    PubMed

    Ferrannini, Ele; Iervasi, Giorgio; Cobb, Jeff; Ndreu, Rudina; Nannipieri, Monica

    2017-02-28

    While hyper/hypothyroidism causes dysglycemia, the relationship between thyroid hormone levels within the normal range and insulin resistance (IR) is unclear. In 940 participants with strictly normal serum concentrations of free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH)) followed up for 3 years, we measured insulin sensitivity (by the insulin clamp technique) and a panel of 35 circulating metabolites. At baseline, across quartiles of increasing fT3 levels (or fT3/fT4 ratio) there emerged most features of IR (male sex, higher BMI, waist circumference, heart rate, blood pressure, fatty liver index, free fatty acids, and triglycerides levels, reduced insulin-mediated glucose disposal and ß-cell glucose sensitivity). In multiadjusted analyses, fT3 was reciprocally related to insulin sensitivity and, in a subset of 303 subjects, directly related to endogenous glucose production. In multiple regression models adjusting for sex, age, BMI and baseline value of insulin sensitivity, higher baseline fT3 levels were significant predictors of the decreases in insulin sensitivity. Moreover, baseline fT3 predicted follow-up increases in glycemia independently of sex, age, BMI, insulin sensitivity, ß-cell glucose sensitivity and baseline glycemia. Serum tyrosine levels were higher in IR and were directly associated with fT3; higher α-hydroxybutyrate levels signaled enhanced oxidative stress impairing tyrosine degradation. In 25 morbidly obese patients, surgery-induced weight loss improved IR and consensually lowered fT3 High-normal fT3 levels are associated with IR both cross-sectionally and longitudinally, and predict deterioration of glucose tolerance. This association is supported by a metabolite pattern that points at increased oxidative stress as part of the IR syndrome.

  9. Sunlight-Exposed Biofilm Microbial Communities Are Naturally Resistant to Chernobyl Ionizing-Radiation Levels

    PubMed Central

    Ragon, Marie; Restoux, Gwendal; Moreira, David; Møller, Anders Pape; López-García, Purificación

    2011-01-01

    Background The Chernobyl accident represents a long-term experiment on the effects of exposure to ionizing radiation at the ecosystem level. Though studies of these effects on plants and animals are abundant, the study of how Chernobyl radiation levels affect prokaryotic and eukaryotic microbial communities is practically non-existent, except for a few reports on human pathogens or soil microorganisms. Environments enduring extreme desiccation and UV radiation, such as sunlight exposed biofilms could in principle select for organisms highly resistant to ionizing radiation as well. Methodology/Principal Findings To test this hypothesis, we explored the diversity of microorganisms belonging to the three domains of life by cultivation-independent approaches in biofilms developing on concrete walls or pillars in the Chernobyl area exposed to different levels of radiation, and we compared them with a similar biofilm from a non-irradiated site in Northern Ireland. Actinobacteria, Alphaproteobacteria, Bacteroidetes, Acidobacteria and Deinococcales were the most consistently detected bacterial groups, whereas green algae (Chlorophyta) and ascomycete fungi (Ascomycota) dominated within the eukaryotes. Close relatives to the most radio-resistant organisms known, including Rubrobacter species, Deinococcales and melanized ascomycete fungi were always detected. The diversity of bacteria and eukaryotes found in the most highly irradiated samples was comparable to that of less irradiated Chernobyl sites and Northern Ireland. However, the study of mutation frequencies in non-coding ITS regions versus SSU rRNA genes in members of a same actinobacterial operational taxonomic unit (OTU) present in Chernobyl samples and Northern Ireland showed a positive correlation between increased radiation and mutation rates. Conclusions/Significance Our results show that biofilm microbial communities in the most irradiated samples are comparable to non-irradiated samples in terms of general

  10. Decreased levels of inflammatory cytokines in immunoglobulin-resistant Kawasaki disease after plasma exchange.

    PubMed

    Fujimaru, Takuya; Ito, Shuichi; Masuda, Hiroshi; Oana, Shinji; Kamei, Koichi; Ishiguro, Akira; Kato, Hitoshi; Abe, Jun

    2014-12-01

    The pathogenesis of coronary artery aneurysm (CAA) formation in Kawasaki disease (KD) remains unknown. However, inflammatory cytokines are thought to play an important role in KD. Patients with intravenous immunoglobulin (IVIG)-resistant KD are more likely to develop CAA. For such refractory patients, steroids and emerging infliximab (IFX) are used; however, further verification is required for their efficacy and safety. Plasma exchange (PE), which removes various inflammatory cytokines, has been used in Japan for over 15 years to prevent CAA in IVIG-resistant KD patients. The sequential change in inflammatory cytokines during the time course of PE has yet to be investigated. In this study, we measured plasma levels of 13 cytokines in nine children with IVIG-resistant KD before the start of PE (day 0: D0), as well as at 1 or 2 days (D1/2), and 4 or 5 days (D4/5) after starting PE. The median age of onset was 8 months (range: 3-53 months). Before PE, patients were treated with IVIG (median dose: 4 g/kg, range: 3-4 g/kg). The median starting period of PE was 8 days after the onset of fever (range: 6-21 days), while its duration was 3 days (range: 2-5 days). Among the 13 cytokines, interleukin-6, tumor necrosis factor-α, tumor necrosis factor receptor I (TNFR1), TNFR2, granulocyte colony-stimulating factor, and IL-17 were significantly lower at D4/5 compared with D0 and/or D1/2, reflecting the potential central efficacy of PE. While three patients developed moderate CAA, their condition regressed within 1 year. The removal of inflammatory cytokines could be the central efficacy of PE against refractory KD.

  11. Skeletal Adaptations to Different Levels of Eccentric Resistance Following Eight Weeks of Training

    NASA Technical Reports Server (NTRS)

    English, Kirk L.; Loehr, James A.; Lee, Stuart M. C.; Maddocks, Mary J.; Laughlin, Mitzi S.; Hagan, R. Donald

    2007-01-01

    Coupled concentric-eccentric resistive exercise maintains bone mineral density (BMD) during bed rest and aging. PURPOSE: We hypothesized that 8 wks of lower body resistive exercise training with higher ratios of eccentric to concentric loading would enhance hip and lumbar BMD. METHODS: Forty untrained male volunteers (34.9+/-7.0 yrs, 80.9+/-9.8 kg, 178.2+/-7.1 cm; mean+/-SD) were matched for leg press (LP) 1-Repetition Maximum (1-RM) strength and randomly assigned to one of 5 training groups. Concentric load (% 1-RM) was constant across groups, but each group trained with different levels of eccentric load (0, 33, 66, 100, or 138% of concentric) for all training sessions. Subjects performed a periodized supine LP and heel raise (HR) training program 3 d wk-1 for 8 wks using a modified Agaton Fitness System (Agaton Fitness AB, Boden, Sweden). Hip and lumbar BMD (g/sq cm) was measured in triplicate pre- and post-training using DXA (Hologic Discovery ). Pre- and post-training means were compared using the appropriate ANOVA and Tukey's post hoc tests. Within group pre- to post-training BMD was compared using paired t-tests with a Bonferroni adjustment. RESULTS: There was a main effect of training on L1, L2, L3, L4, total lumbar, and greater trochanter BMD, but there were no differences between groups. CONCLUSION: Eights wks of lower body resistive exercise increased greater trochanter and lumbar BMD. Inability to detect group differences may have been influenced by a potentially osteogenic vibration associated with device operation in the 0, 33, and 66% groups.

  12. Rice Responses and Resistance to Planthopper-Borne Viruses at Transcriptomic and Proteomic Levels.

    PubMed

    Cui, Feng; Zhao, Wan; Luo, Lan; Kang, Le

    2016-01-01

    Rice (Oryza sativa) is one of the most important cereal crops in the world, especially in Asian areas. Rice virus diseases are considered as the most serious threat to rice yields. Most rice viruses are transmitted by hemipteran insects such as planthoppers and leafhoppers. In Asia five rice viruses are transmitted mainly by three planthopper species in a persistent manner: Rice stripe virus, Rice black-streaked dwarf virus, Rice ragged stunt virus, Rice grassy stunt virus, and Southern rice black-streaked dwarf virus. In rice antivirus studies, several individual genes have been shown to function in rice resistance to viruses. Since plant responses to viral infection are complex, system-level omic studies are required to fully understand the responses. Recently more and more omic studies have appeared in the literatures on relationships between planthoppers and viruses, employing microarray, RNA-Seq, small RNA deep sequencing, degradome sequencing, and proteomic analysis. In this paper, we review the current knowledge and progress of omic studies in rice plant responses and resistance to four planthopper-borned viruses. We also discuss progress in the omic study of the interactions of planthoppers and rice viruses. Future research directions and translational applications of fundamental knowledge of virus-vector-rice interactions are proposed.

  13. Disparities in capreomycin resistance levels associated with the rrs A1401G mutation in clinical isolates of Mycobacterium tuberculosis.

    PubMed

    Reeves, Analise Z; Campbell, Patricia J; Willby, Melisa J; Posey, James E

    2015-01-01

    As the prevalence of multidrug-resistant and extensively drug-resistant tuberculosis strains continues to rise, so does the need to develop accurate and rapid molecular tests to complement time-consuming growth-based drug susceptibility testing. Performance of molecular methods relies on the association of specific mutations with phenotypic drug resistance and while considerable progress has been made for resistance detection of first-line antituberculosis drugs, rapid detection of resistance for second-line drugs lags behind. The rrs A1401G allele is considered a strong predictor of cross-resistance between the three second-line injectable drugs, capreomycin (CAP), kanamycin, and amikacin. However, discordance is often observed between the rrs A1401G mutation and CAP resistance, with up to 40% of rrs A1401G mutants being classified as CAP susceptible. We measured the MICs to CAP in 53 clinical isolates harboring the rrs A1401G mutation and found that the CAP MICs ranged from 8 μg/ml to 40 μg/ml. These results were drastically different from engineered A1401G mutants generated in isogenic Mycobacterium tuberculosis, which exclusively exhibited high-level CAP MICs of 40 μg/ml. These data support the results of prior studies, which suggest that the critical concentration of CAP (10 μg/ml) used to determine resistance by indirect agar proportion may be too high to detect all CAP-resistant strains and suggest that a larger percentage of resistant isolates could be identified by lowering the critical concentration. These data also suggest that differences in resistance levels among clinical isolates are possibly due to second site or compensatory mutations located elsewhere in the genome.

  14. Emergence of High-Level Daptomycin Resistance in Corynebacterium striatum in Two Patients with Left Ventricular Assist Device Infections

    PubMed Central

    Werth, Brian J.; Hahn, William O.; Butler-Wu, Susan M.

    2016-01-01

    Introduction: We describe the clinical and microbiologic courses of two patients with ventricular assist device infections secondary to Corynebacterium striatum treated with daptomycin. In both cases, the pathogen was initially susceptible to daptomycin (minimum inhibitory concentration [MIC] <0.125 mg/L) but became resistant (MIC >256 mg/L) during therapy. Methods: The clonal nature of the isolates was determined by pulse-field gel electrophoresis (PFGE). Daptomycin binding was assessed by fluorescence microscopy using daptomycin–boron-dipyrromethene (bodipy). Induction and stability of daptomycin resistance were assessed by culturing strains in the presence of low concentrations of daptomycin or passage of resistant strains on daptomycin-free medium and repeat MIC testing, respectively. Results: PFGE revealed that resistant clinical isolates were genetically indistinguishable from their parent strains, but the two pairs were unrelated to each other. The resistant strains had 7.5–15 times lower binding of daptomycin-bodipy compared to the related susceptible strains (p ≤ 0.0002). High-level daptomycin resistance (MIC >256 mg/L) was generated in vitro for both susceptible parent strains after overnight culture in the presence of daptomycin. One of the resistant strains maintained a high-level resistance phenotype up to 5 days of passage on daptomycin-free medium, whereas the other strain reverted back to a susceptible phenotype (MIC = 0.38 mg/L) after one passage on daptomycin-free medium, with a concomitant increase in daptomycin binding. Conclusions: High-level daptomycin resistance in C. striatum was readily generated in vitro and during the course of therapy in these patients. This resistance appears to be mediated by reduced daptomycin binding. Providers should be cautious about using long-term daptomycin monotherapy for C. striatum infections. PMID:26544621

  15. Resistance of Feather-Associated Bacteria to Intermediate Levels of Ionizing Radiation near Chernobyl.

    PubMed

    Ruiz-González, Mario Xavier; Czirják, Gábor Árpád; Genevaux, Pierre; Møller, Anders Pape; Mousseau, Timothy Alexander; Heeb, Philipp

    2016-03-15

    Ionizing radiation has been shown to produce negative effects on organisms, although little is known about its ecological and evolutionary effects. As a study model, we isolated bacteria associated with feathers from barn swallows Hirundo rustica from three study areas around Chernobyl differing in background ionizing radiation levels and one control study site in Denmark. Each bacterial community was exposed to four different γ radiation doses ranging from 0.46 to 3.96 kGy to test whether chronic exposure to radiation had selected for resistant bacterial strains. Experimental radiation duration had an increasingly overall negative effect on the survival of all bacterial communities. After exposure to γ radiation, bacteria isolated from the site with intermediate background radiation levels survived better and produced more colonies than the bacterial communities from other study sites with higher or lower background radiation levels. Long-term effects of radiation in natural populations might be an important selective pressure on traits of bacteria that facilitate survival in certain environments. Our findings indicate the importance of further studies to understand the proximate mechanisms acting to buffer the negative effects of ionizing radiation in natural populations.

  16. Resistance of Feather-Associated Bacteria to Intermediate Levels of Ionizing Radiation near Chernobyl

    PubMed Central

    Ruiz-González, Mario Xavier; Czirják, Gábor Árpád; Genevaux, Pierre; Møller, Anders Pape; Mousseau, Timothy Alexander; Heeb, Philipp

    2016-01-01

    Ionizing radiation has been shown to produce negative effects on organisms, although little is known about its ecological and evolutionary effects. As a study model, we isolated bacteria associated with feathers from barn swallows Hirundo rustica from three study areas around Chernobyl differing in background ionizing radiation levels and one control study site in Denmark. Each bacterial community was exposed to four different γ radiation doses ranging from 0.46 to 3.96 kGy to test whether chronic exposure to radiation had selected for resistant bacterial strains. Experimental radiation duration had an increasingly overall negative effect on the survival of all bacterial communities. After exposure to γ radiation, bacteria isolated from the site with intermediate background radiation levels survived better and produced more colonies than the bacterial communities from other study sites with higher or lower background radiation levels. Long-term effects of radiation in natural populations might be an important selective pressure on traits of bacteria that facilitate survival in certain environments. Our findings indicate the importance of further studies to understand the proximate mechanisms acting to buffer the negative effects of ionizing radiation in natural populations. PMID:26976674

  17. Dominant Functional Group Effects on the Invasion Resistance at Different Resource Levels

    PubMed Central

    Wang, Jiang; Ge, Yuan; Zhang, Chong B.; Bai, Yi; Du, Zhao K.

    2013-01-01

    Background Functional group composition may affect invasion in two ways the effect of abundance, i.e. dominance of functional group; and the effect of traits, i.e. identity of functional groups. However, few studies have focused on the role of abundance of functional group on invasion resistance. Moreover, how resource availability influences the role of the dominant functional group in invasion resistance is even less understood. Methodology/Principal Findings In this experiment, we established experimental pots using four different functional groups (annual grass, perennial grass, deciduous shrub or arbor and evergreen shrub or arbor), and the dominant functional group was manipulated. These experimental pots were respectively constructed at different soil nitrogen levels (control and fertilized). After one year of growth, we added seeds of 20 different species (five species per functional group) to the experimental pots. Fertilization significantly increased the overall invasion success, while dominant functional group had little effect on overall invasion success. When invaders were grouped into functional groups, invaders generally had lower success in pots dominated by the same functional group in the control pots. However, individual invaders of the same functional group exhibited different invasion patterns. Fertilization generally increased success of invaders in pots dominated by the same than by another functional group. However, fertilization led to great differences for individual invaders. Conclusions/Significance The results showed that the dominant functional group, independent of functional group identity, had a significant effect on the composition of invaders. We suggest that the limiting similarity hypothesis may be applicable at the functional group level, and limiting similarity may have a limited role for individual invaders as shown by the inconsistent effects of dominant functional group and fertilization. PMID:24167565

  18. Installation and Commissioning of a 6-Tesla Superconducting Wavelength Shifter at Taiwan Light Source

    NASA Astrophysics Data System (ADS)

    Chang, C. H.; Chang, H. P.; Chen, Jenny; Chen, J. R.; Fan, T. C.; Hwang, C. S.; Hsiung, G. Y.; Hsu, K. T.; Kuo, C. C.; Luo, G. H.; Wang, D. J.; Wang, M. H.

    2005-09-01

    The Taiwan Light Source (TLS) is the first third-generation light source in Asia. The storage ring has six straight sections one section for injection, one for the RF cavities and diagnostic instrumentation and four sections for insertion devices, which are U5, U9, EPU and W20. Generating high-energy X-ray photons is a high priority at TLS. A single hybrid type wiggler is associated with three beam lines to serve X-ray users. The installed Superconducting Wavelength Shifter (SWLS) is very compact in size and can produce very high-energy photons. The injection section at TLS can barely accommodate the SWLS. The expected multipole components of the SWLS are strong, shrink the dynamic aperture; perturb the beta function, and reduce the beam lifetime. The increase in the synchrotron radiation by the SWLS also changes beam emittance and increases the energy spread. The influence of SWLS on the low-energy, 1.5 GeV, storage-ring should not be neglected. The downstream kicker with the water-cooled copper mask must be modified to prevent a potential meltdown of the welding junction of the ceramic chamber because the heat load is high. The 1.2 μs half-sine pulse field of the kicker is then altered by the copper-made radiation mask, which is installed inside the ceramic chamber. The operating capability of cryogenic system is established to ensure the smooth commissioning of the SWLS. The magnetic field mapping, the dynamic aperture simulation data and commissioning results will be presented and discussed herein.

  19. Effect of zinc supplementation on serum leptin levels and insulin resistance of obese women.

    PubMed

    Marreiro, Dilina do Nascimento; Geloneze, Bruno; Tambascia, Marcos A; Lerário, Antonio C; Halpern, Alfredo; Cozzolino, Silvia Maria Franciscato

    2006-08-01

    Leptin is thought to be a lipostatic signal that contributes to body weight regulation. Zinc might play an important role in appetite regulation and its administration stimulates leptin production. However, there are few reports in the literature on its role on leptin levels in the obese population. The present work assesses the effect of zinc supplementation on serum leptin levels in insulin resistance (IR). A prospective double-blind, randomized, clinical, placebo-controlled study was conducted. Fifty-six normal glucose-tolerant obese women (age: 25-45 yr, body mass index [BMI] = 36.2 +/- 2.3 kg/m2) were randomized for treatment with 30 mg zinc daily for 4 wk. Baseline values of both groups were similar for age, BMI, caloric intake, insulin concentration, insulin resistance, and zinc concentration in diet, plasma, urine, and erythrocytes. Insulin and leptin were measured by radioimmunoassay and IR was estimated by the homeostasis model assessment (HOMA). The determinations of zinc in plasma, erythrocytes, and 24- h urine were performed by using atomic absorption spectrophotometry. After 4 wk, BMI, fasting glucose, and zinc concentration in plasma and erythrocyte did not change in either group, although zinc concentration in the urine increased from 385.9 +/- 259.3 to 470.2 +/- 241.2 +/- microg/24 h in the group with zinc supplementation (p < 0.05). Insulin did not change in the placebo group, whereas there was a significant decrease of this hormone in the supplemented group. HOMA also decreased from 5.8 +/- 2.6 to 4.3 +/- 1.7 (p < 0.05) in the zinc-supplemented group but did not change in the placebo group. Leptin did not change in the placebo group. In the zinc group, leptin was 23.6 +/- 12.3 microg/L and did not change. More human data from a unique population of obese individuals with documented insulin resistance would be useful in guiding future studies on zinc supplementation (with higher doses or longer intervals) or different measures.

  20. Genetic basis of high level aminoglycoside resistance in Acinetobacter baumannii from Beijing, China

    PubMed Central

    Nie, Lu; Lv, Yuemeng; Yuan, Min; Hu, Xinxin; Nie, Tongying; Yang, Xinyi; Li, Guoqing; Pang, Jing; Zhang, Jingpu; Li, Congran; Wang, Xiukun; You, Xuefu

    2014-01-01

    The objective of this study was to investigate the genetic basis of high level aminoglycoside resistance in Acinetobacter baumannii clinical isolates from Beijing, China. 173 A. baumannii clinical isolates from hospitals in Beijing from 2006 to 2009 were first subjected to high level aminoglycoside resistance (HLAR, MIC to gentamicin and amikacin>512 µg/mL) phenotype selection by broth microdilution method. The strains were then subjected to genetic basis analysis by PCR detection of the aminoglycoside modifying enzyme genes (aac(3)-I, aac(3)-IIc, aac(6′)-Ib, aac(6′)-II, aph(4)-Ia, aph(3′)-I, aph(3′)-IIb, aph(3′)-IIIa, aph(3′)-VIa, aph(2″)-Ib, aph(2″)-Ic, aph(2″)-Id, ant(2″)-Ia, ant(3″)-I and ant(4′)-Ia) and the 16S rRNA methylase genes (armA, rmtB and rmtC). Correlation analysis between the presence of aminoglycoside resistance gene and HLAR phenotype were performed by SPSS. Totally 102 (58.96%) HLAR isolates were selected. The HLAR rates for year 2006, 2007, 2008 and 2009 were 52.63%, 65.22%, 51.11% and 70.83%, respectively. Five modifying enzyme genes (aac(3)-I, detection rate of 65.69%; aac(6′)-Ib, detection rate of 45.10%; aph(3′)-I, detection rate of 47.06%; aph(3′)-IIb, detection rate of 0.98%; ant(3″)-I, detection rate of 95.10%) and one methylase gene (armA, detection rate of 98.04%) were detected in the 102 A. baumannii with aac(3)-I+aac(6′)-Ib+ant(3″)-I+armA (detection rate of 25.49%), aac(3)-I+aph(3′)-I+ant(3″)-I+armA (detection rate of 21.57%) and ant(3″)-I+armA (detection rate of 12.75%) being the most prevalent gene profiles. The values of chi-square tests showed correlation of armA, ant(3″)-I, aac(3)-I, aph(3′)-I and aac(6′)-Ib with HLAR. armA had significant correlation (contingency coefficient 0.685) and good contingency with HLAR (kappa 0.940). The high rates of HLAR may cause a serious problem for combination therapy of aminoglycoside with β-lactams against A. baumannii infections. As armA was

  1. How should we be determining background and baseline antibiotic resistance levels in agroecosystem research?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although historically antibiotic resistance has occurred naturally in environmental bacteria, many questions remain regarding the specifics of how humans and animals contribute to the development and spread of antibiotic resistance in agroecosystems. Additional research is necessary to completely u...

  2. High level of resistance to aztreonam and ticarcillin in Pseudomonas aeruginosa isolated from soil of different crops in Brazil.

    PubMed

    Pitondo-Silva, André; Martins, Vinicius Vicente; Fernandes, Ana Flavia Tonelli; Stehling, Eliana Guedes

    2014-03-01

    Pseudomonas aeruginosa can be found in water, soil, plants and, human and animal fecal samples. It is an important nosocomial pathogenic agent characterized by an intrinsic resistance to multiple antimicrobial agents and the ability to develop high-level (acquired) multidrug resistance through some mechanisms, among them, by the acquisition of plasmids and integrons, which are mobile genetic elements. In this study, 40 isolates from Brazilian soil were analyzed for antibiotic resistance, presence of integrons and plasmidial profile. The results demonstrated that the vast majority of the isolates have shown resistance for aztreonam (92.5%, n=37) and ticarcillin (85%, n=34), four isolates presented plasmids and eight isolates possess the class 1 integron. These results demonstrated that environmental isolates of P. aeruginosa possess surprising antibiotic resistance profile to aztreonam and ticarcillin, two antimicrobial agents for clinical treatment of cystic fibrosis patients and other infections occurred by P. aeruginosa.

  3. Paclitaxel-resistant HeLa cells have up-regulated levels of reactive oxygen species and increased expression of taxol resistance gene 1.

    PubMed

    Bi, Wenxiang; Wang, Yuxia; Sun, Gaoying; Zhang, Xiaojin; Wei, Yongqing; Li, Lu; Wang, Xiaoyuan

    2014-07-01

    This study is to establish a paclitaxel (PTX)-resistant human cervical carcinoma HeLa cell line (HeLa/PTX) and to investigate its redox characteristics and the expression of taxol resistance gene 1 (Txr1). HeLa cells were treated with PTX and effects of PTX on cell proliferation were detected through cell counting and the MTT assay. Levels of cellular reactive oxygen species (ROS), reduced glutathione (GSH), and oxidized glutathione (GSSG) as well as the ratio of GSH to GSSG were measured by the 2,7-difluorescein diacetate (DCFH-DA) method and the 5,5'dithiobis(2-nitrobenzoic acid) (DTNB) method. Activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined by the nitrite formation method, the molybdate colorimetric method, and the DTNB colorimetric method, respectively. The level of Txr1 mRNA was determined by real-time PCR. Compared with the regular HeLa cells, HeLa/PTX cells were larger in size and had more cytoplasmic granules. The population doubling time for HeLa/PTX cells was 1.32 times of that of HeLa cells (P<0.01). HeLa/PTX cells showed stronger resistance to PTX than HeLa cells with a resistance index of 122.69. HeLa/PTX cells had higher levels of ROS (P<0.01) and Txr1 mRNA (P<0.01), lower level of GSH (P < 0.05), and lower activities of SOD (P<0.01) and GPx (P < 0.05) than HeLa cells. HeLa/PTX cells, with higher levels of ROS and Txr1 mRNA expression, are more resistant to PTX than HeLa cells.

  4. Repression of Invasion Genes and Decreased Invasion in a High-Level Fluoroquinolone-Resistant Salmonella Typhimurium Mutant

    PubMed Central

    Fàbrega, Anna; du Merle, Laurence; Le Bouguénec, Chantal; Jiménez de Anta, M. Teresa; Vila, Jordi

    2009-01-01

    Background Nalidixic acid resistance among Salmonella Typhimurium clinical isolates has steadily increased, whereas the level of ciprofloxacin resistance remains low. The main objective of this study was to characterize the fluoroquinolone resistance mechanisms acquired in a S. Typhimurium mutant selected with ciprofloxacin from a susceptible isolate and to investigate its invasion ability. Methodology/Principal Findings Three different amino acid substitutions were detected in the quinolone target proteins of the resistant mutant (MIC of ciprofloxacin, 64 µg/ml): D87G and G81C in GyrA, and a novel mutation, E470K, in ParE. A protein analysis revealed an increased expression of AcrAB/TolC and decreased expression of OmpC. Sequencing of the marRAB, soxRS, ramR and acrR operons did not show any mutation and neither did their expression levels in a microarray analysis. A decreased percentage of invasion ability was detected when compared with the susceptible clinical isolate in a gentamicin protection assay. The microarray results revealed a decreased expression of genes which play a role during the invasion process, such as hilA, invF and the flhDC operon. Of note was the impaired growth detected in the resistant strain. A strain with a reverted phenotype (mainly concerning the resistance phenotype) was obtained from the resistant mutant. Conclusions/Significance In conclusion, a possible link between fluoroquinolone resistance and decreased cell invasion ability may exist explaining the low prevalence of fluoroquinolone-resistant S. Typhimurium clinical isolates. The impaired growth may appear as a consequence of fluoroquinolone resistance acquisition and down-regulate the expression of the invasion genes. PMID:19946377

  5. Systems-level analysis of Escherichia coli response to silver nanoparticles: the roles of anaerobic respiration in microbial resistance.

    PubMed

    Du, Huamao; Lo, Tat-Ming; Sitompul, Johnner; Chang, Matthew Wook

    2012-08-10

    Despite extensive use of silver nanoparticles for antimicrobial applications, cellular mechanisms underlying microbial response to silver nanoparticles remain to be further elucidated at the systems level. Here, we report systems-level response of Escherichia coli to silver nanoparticles using transcriptome-based biochemical and phenotype assays. Notably, we provided the evidence that anaerobic respiration is induced upon exposure to silver nanoparticles. Further we showed that anaerobic respiration-related regulators and enzymes play an important role in E. coli resistance to silver nanoparticles. In particular, our results suggest that arcA is essential for resistance against silver NPs and the deletion of fnr, fdnH and narH significantly increases the resistance. We envision that this study offers novel insights into modes of antimicrobial action of silver nanoparticles, and cellular mechanisms contributing to the development of microbial resistance to silver nanoparticles.

  6. High-level and novel mechanisms of carbapenem resistance in Gram-negative bacteria from tertiary hospitals in Nigeria.

    PubMed

    Ogbolu, D O; Webber, M A

    2014-05-01

    To determine the occurrence and molecular basis of carbapenem resistance in Gram-negative bacteria from tertiary hospitals in Nigeria, 182 non-duplicate Gram-negative bacterial isolates were investigated for antimicrobial susceptibility, presence of carbapenemases (tested phenotypically and genotypically), random amplified polymorphic DNA (RAPD) typing, plasmid sizing and replicon typing. Minimum inhibitory concentrations of carbapenems showed a high degree of resistance, with 67 isolates (36.8%) being resistant to all carbapenems, of which 40 (59.7%) produced enzymes able to hydrolyse imipenem. PCR and sequencing identified only 10 isolates (5.5%) carrying known carbapenemase genes, including bla(NDM), bla(VIM) and bla(GES). The majority of phenotypically carbapenem-resistant and carbapenemase-producing isolates did not carry a known carbapenemase gene. Transconjugant or transformant plasmid sizes were estimated to be 115 kb for bla(NDM)- and 93 kb for bla(VIM)-carrying plasmids. These plasmids were untypeable for replicon/incompatibility and transferred various other genes including plasmid-mediated quinolone resistance (PMQR) genes and bla(CTX-M-15). Typing showed that the isolates in this study were not clonally related. There is a high level of carbapenem resistance in Nigeria. As well as the globally relevant carbapenemases (bla(NDM), bla(VIM) and bla(GES)), there are other unknown gene(s) or variant(s) in circulation able to hydrolyse carbapenems and confer high-level resistance.

  7. Herd-level association between antimicrobial use and antimicrobial resistance in bovine mastitis Staphylococcus aureus isolates on Canadian dairy farms.

    PubMed

    Saini, V; McClure, J T; Scholl, D T; DeVries, T J; Barkema, H W

    2012-04-01

    Surveillance of antimicrobial use and resistance is needed to manage antimicrobial resistance in bacteria. In this study, data were collected on antimicrobial use and resistance in Staphylococcus aureus (n=562), isolated from intramammary infections and (sub)clinical mastitis cases on 89 dairy farms in 4 regions of Canada [Alberta, Ontario, Québec, and the Maritime Provinces (Prince Edward Island, Nova Scotia, and New Brunswick)]. Dairy producers were asked to deposit empty drug containers into specially provided receptacles, and antimicrobial drug use rate was calculated to quantify antimicrobial use. Minimum inhibitory concentrations were determined using the Sensititer bovine mastitis plate system (TREK Diagnostic Systems Inc., Cleveland, OH), containing antimicrobials commonly used for mastitis treatment and control. Multivariable logistic regression models were built to determine herd-level risk factors of penicillin, ampicillin, pirlimycin, penicillin-novobiocin combination, tetracycline and sulfadimethoxine resistance in Staph. aureus isolates. Intramammary administration of the penicillin-novobiocin combination for dry cow therapy was associated with penicillin and ampicillin resistance [odds ratio (OR): 2.17 and 3.10, respectively]. Systemic administration of penicillin was associated with penicillin resistance (OR: 1.63). Intramammary administration of pirlimycin for lactating cow mastitis treatment was associated with pirlimycin resistance as well (OR: 2.07). Average herd parity was associated with ampicillin and tetracycline resistance (OR: 3.88 and 0.02, respectively). Average herd size was also associated with tetracycline resistance (OR: 1.02). Dairy herds in the Maritime region had higher odds of penicillin and lower odds of ampicillin resistance than dairy herds in Québec (OR: 2.18 and 0.19, respectively). Alberta dairy herds had lower odds of ampicillin and sulfadimethoxine resistance than dairy herds in Québec (OR: 0.04 and 0.08, respectively

  8. Triband phase shifter design using split-ring resonator and complementary split-ring resonator-loaded ground plane for wireless applications

    NASA Astrophysics Data System (ADS)

    Kulandhaisamy, Indhumathi; Shrivastav, Arun Kumar; Kanagasabai, Malathi; Kizhekke Pakkathillam, Jayaram

    2015-10-01

    This paper presents the design of a novel linear analog planar phase shifter deploying split-ring resonator (SRR) and complementary split-ring resonator (CSRR) structures. Based on the advantages of these structures, a triband phase shifter is designed for multiple target systems to operate at 0.85, 1.69, and 2.46 GHz bands finding applications for European RFIDs, Satellite Radio Broadcast System, Mobile Services, and ISM Band, respectively. The effect of SRR and CSRR coupling with host transmission line is also analyzed on the basis of Bloch mode theory and the modes are validated through Eigen mode analysis. The proposed phase shifter design shows a good agreement between simulated and measured results. A 90° ± 8° shift in phase is observed at lower and upper bands, and a 135° ± 8° shift is observed in center band with reasonable group delay components.

  9. Global metabolic analyses identify key differences in metabolite levels between polymyxin-susceptible and polymyxin-resistant Acinetobacter baumannii.

    PubMed

    Maifiah, Mohd Hafidz Mahamad; Cheah, Soon-Ee; Johnson, Matthew D; Han, Mei-Ling; Boyce, John D; Thamlikitkul, Visanu; Forrest, Alan; Kaye, Keith S; Hertzog, Paul; Purcell, Anthony W; Song, Jiangning; Velkov, Tony; Creek, Darren J; Li, Jian

    2016-02-29

    Multidrug-resistant Acinetobacter baumannii presents a global medical crisis and polymyxins are used as the last-line therapy. This study aimed to identify metabolic differences between polymyxin-susceptible and polymyxin-resistant A. baumannii using untargeted metabolomics. The metabolome of each A. baumannii strain was measured using liquid chromatography-mass spectrometry. Multivariate and univariate statistics and pathway analyses were employed to elucidate metabolic differences between the polymyxin-susceptible and -resistant A. baumannii strains. Significant differences were identified between the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii strains. The lipopolysaccharide (LPS) deficient, polymyxin-resistant 19606R showed perturbation in specific amino acid and carbohydrate metabolites, particularly pentose phosphate pathway (PPP) and tricarboxylic acid (TCA) cycle intermediates. Levels of nucleotides were lower in the LPS-deficient 19606R. Furthermore, 19606R exhibited a shift in its glycerophospholipid profile towards increased abundance of short-chain lipids compared to the parent polymyxin-susceptible ATCC 19606. In contrast, in a pair of clinical isolates 03-149.1 (polymyxin-susceptible) and 03-149.2 (polymyxin-resistant, due to modification of lipid A), minor metabolic differences were identified. Notably, peptidoglycan biosynthesis metabolites were significantly depleted in both of the aforementioned polymyxin-resistant strains. This is the first comparative untargeted metabolomics study to show substantial differences in the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii.

  10. Global metabolic analyses identify key differences in metabolite levels between polymyxin-susceptible and polymyxin-resistant Acinetobacter baumannii

    PubMed Central

    Mahamad Maifiah, Mohd Hafidz; Cheah, Soon-Ee; Johnson, Matthew D.; Han, Mei-Ling; Boyce, John D.; Thamlikitkul, Visanu; Forrest, Alan; Kaye, Keith S.; Hertzog, Paul; Purcell, Anthony W.; Song, Jiangning; Velkov, Tony; Creek, Darren J.; Li, Jian

    2016-01-01

    Multidrug-resistant Acinetobacter baumannii presents a global medical crisis and polymyxins are used as the last-line therapy. This study aimed to identify metabolic differences between polymyxin-susceptible and polymyxin-resistant A. baumannii using untargeted metabolomics. The metabolome of each A. baumannii strain was measured using liquid chromatography-mass spectrometry. Multivariate and univariate statistics and pathway analyses were employed to elucidate metabolic differences between the polymyxin-susceptible and -resistant A. baumannii strains. Significant differences were identified between the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii strains. The lipopolysaccharide (LPS) deficient, polymyxin-resistant 19606R showed perturbation in specific amino acid and carbohydrate metabolites, particularly pentose phosphate pathway (PPP) and tricarboxylic acid (TCA) cycle intermediates. Levels of nucleotides were lower in the LPS-deficient 19606R. Furthermore, 19606R exhibited a shift in its glycerophospholipid profile towards increased abundance of short-chain lipids compared to the parent polymyxin-susceptible ATCC 19606. In contrast, in a pair of clinical isolates 03–149.1 (polymyxin-susceptible) and 03–149.2 (polymyxin-resistant, due to modification of lipid A), minor metabolic differences were identified. Notably, peptidoglycan biosynthesis metabolites were significantly depleted in both of the aforementioned polymyxin-resistant strains. This is the first comparative untargeted metabolomics study to show substantial differences in the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii. PMID:26924392

  11. Dietary fish oil positively regulates plasma leptin and adiponectin levels in sucrose-fed, insulin-resistant rats.

    PubMed

    Rossi, Andrea S; Lombardo, Yolanda B; Lacorte, Jean-Marc; Chicco, Adriana G; Rouault, Christine; Slama, Gérard; Rizkalla, Salwa W

    2005-08-01

    Insulin resistance and adiposity induced by a long-term sucrose-rich diet (SRD) in rats could be reversed by fish oil (FO). Regulation of plasma leptin and adiponectin levels, as well as their gene expression, by FO might be implicated in these findings. This study was designed to evaluate the long-term regulation of leptin and adiponectin by dietary FO in a dietary model of insulin resistance induced by long-term SRD in rats and to determine their impact on adiposity and insulin sensitivity. Rats were randomized to consume a control diet (CD; n = 25) or an SRD (n = 50) for 7 mo. Subsequently, the SRD-fed rats were randomized to consume SRD+FO or to continue on SRD for an additional 2 mo. Long-term SRD induced overweight and decreased both plasma leptin and adiponectin levels without change in gene expression. Dyslipidemia, adiposity, and insulin resistance accompanied these modifications. Shifting the source of fat to FO for 2 mo increased plasma levels of both adipokines, reversed insulin resistance and dyslipidemia, and improved adiposity. These results were not associated with modifications in gene expression. These results suggest that increasing both adipokines by dietary FO might play an essential role in the normalization of insulin resistance and adiposity in dietary-induced, insulin-resistant models.

  12. Country-level operational implementation of the Global Plan for Insecticide Resistance Management.

    PubMed

    Hemingway, Janet; Vontas, John; Poupardin, Rodolphe; Raman, Jaishree; Lines, Jo; Schwabe, Chris; Matias, Abrahan; Kleinschmidt, Immo

    2013-06-04

    Malaria control is reliant on the use of long-lasting pyrethroid-impregnated nets and/or indoor residual spraying (IRS) of insecticide. The rapid selection and spread of operationally significant pyrethroid resistance in African malaria vectors threatens our ability to sustain malaria control. Establishing whether resistance is operationally significant is technically challenging. Routine monitoring by bioassay is inadequate, and there are limited data linking resistance selection with changes in disease transmission. The default is to switch insecticides when resistance is detected, but limited insecticide options and resistance to multiple insecticides in numerous locations make this approach unsustainable. Detailed analysis of the resistance situation in Anopheles gambiae on Bioko Island after pyrethroid resistance was detected in this species in 2004, and the IRS program switched to carbamate bendiocarb, has now been undertaken. The pyrethroid resistance selected is a target-site knock-down resistance kdr-form, on a background of generally elevated metabolic activity, compared with insecticide-susceptible A. gambiae, but the major cytochrome P450-based metabolic pyrethroid resistance mechanisms are not present. The available evidence from bioassays and infection data suggests that the pyrethroid resistance mechanisms in Bioko malaria vectors are not operationally significant, and on this basis, a different, long-lasting pyrethroid formulation is now being reintroduced for IRS in a rotational insecticide resistance management program. This will allow control efforts to be sustained in a cost-effective manner while reducing the selection pressure for resistance to nonpyrethroid insecticides. The methods used provide a template for evidence-based insecticide resistance management by malaria control programs.

  13. Bortezomib-resistance is associated with increased levels of proteasome subunits and apoptosis-avoidance

    PubMed Central

    Wu, Yi-Xin; Yang, Jia-Hua; Saitsu, Hirotomo

    2016-01-01

    Bortezomib (BTZ), a proteasome inhibitor, is the first proteasome inhibitor to be used in clinical practice. Here we investigated the mechanisms underlying acquired bortezomib resistance in hepatocellular carcinoma (HCC) cells. Using stepwise selection, we established two acquired bortezomib-resistant HCC cell lines, a bortezomib-resistant HepG2 cell line (HepG2/BTZ) and bortezomib-resistant HuH7 cell line (HuH7/BTZ). The 50% inhibitory concentration values of HepG2/BTZ and HuH7/BTZ were respectively 15- and 39-fold higher than those of parental cell lines. Sequence analysis of the bortezomib-binding pocket in the β5-subunit showed no mutation. However, bortezomib-resistant HCC cells had increased expression of β1 and β5 proteasome subunits. These alterations of proteasome expression were accompanied by a weak degree of proteasome inhibition in bortezomib-resistant cells than that in wild-type cells after bortezomib exposure. Furthermore, bortezomib-resistant HCC cells acquired resistance to apoptosis. Bortezomib up-regulated pro-apoptotic proteins of the Bcl-2 protein family, Bax and Noxa in wild-type HCC cells. However, in bortezomib-resistant HCC cells, resistance to apoptosis was accompanied by loss of the ability to stabilize and accumulate these proteins. Thus, increased expression and increased activity of proteasomes constitute an adaptive and auto regulatory feedback mechanism to allow cells to survive exposure bortezomib. PMID:27769058

  14. Effects of resistance exercise and obesity level on ghrelin and cortisol in men.

    PubMed

    Thomas, Gwendolyn A; Kraemer, William J; Comstock, Brett A; Dunn-Lewis, Courtenay; Volek, Jeff S; Denegar, Craig R; Maresh, Carl M

    2012-06-01

    Resistance exercise (RE) is increasingly recommended by health organizations as a weight management tool. The purpose of this study was to examine the effects of an acute high-volume, whole-body RE protocol on the glucoregulatory and ghrelin response in sedentary obese and lean men. Five World Health Organization (WHO) class 1 obese (body mass index [BMI], 30.00-34.99) (age, 21.6 ± 2.5 years; height, 176.3 ± 3.7 cm; body mass, 97.8 ± 8.58 kg; body fat, 34.7% ± 2.95%), 5 WHO 2 (BMI, 35-39.99)/WHO 3 (BMI, ≥40) obese (age, 20.0 ± 1.4 years; height, 177.7 ± 5.15 cm; body mass, 120.8 ± 10.49 kg; body fat, 40.5% ± 5.82 %), and 9 lean men (age, 20.1 ± 2.1 years; height, 177.8 ± 8.7 cm; body mass, 71.7 ± 5.8 kg; body fat, 14.7% ± 3.54 %) completed an acute RE testing protocol (6 exercises, 3 sets of 10 repetitions at 85%-95% 10-repetition maximum with 120- and 90-second rest periods); and blood samples were collected pre-, mid-, and immediately postexercise and during recovery (+50, +70, and +110). Resistance exercise produced differences over time in cortisol, insulin, and glucose. Group differences were observed for ghrelin, with the WHO class 2/3 group having significantly greater ghrelin levels than the lean group (d = 0.28, P = .009) and the WHO class 1 group (d = 0.39, P = .002). Higher ghrelin was significantly associated with lower cortisol only in obese individuals. In addition, higher growth hormone was associated with lower ghrelin in lean individuals. Results suggest that glucoregulatory homeostasis is altered with increasing levels of obesity and that these alterations may mediate the response of cortisol and ghrelin in response to RE.

  15. Quantitative resistance level (MIC) of Escherichia coli isolated from calves and pigs suffering from enteritis: national resistance monitoring by the BVL.

    PubMed

    Schröer, Ulrike; Kaspar, Heike; Wallmann, Jürgen

    2007-01-01

    National Resistance Monitoring of the Federal Office of Consumer Protection and Food Safety (BVL), which was put into service in 2001, has made it possible to implement a valid and representative database on the basis of which the resistance situation, development and spread in animal pathogens can be evaluated. Escherichia coil (E. coli) strains originating from calves and pigs suffering from enteritis were first included in the investigations in the 2004/2005 study. A total of 258 bovine and 492 porcine E. coli strains were tested using the broth microdilution method to determine the in vitro susceptibility (minimum inhibitory concentration) to 23 (fattening pigs) and 28 (calves, piglets, weaners) different antimicrobial substances. Considerable prevalences of resistance were found for some antimicrobials. The strains originating from both animal species displayed high prevalences of resistance for tetracycline, trimethoprim, trimethoprim/sulfamethoxazole, doxycycline and ampicillin. Reduced susceptibility was detected particularly in the E. coli strains from calves. The data reveal that the resistance level of E. coli strains isolated from cases of enteric disease in calves and pigs is altogether higher than has so far been reported in pathogens causing different diseases and in other food-producing animal species. Based on the results presented, it is possible to assess the current resistance situation for E. coli strains in calves and pigs in Germany. This in turn helps to deduce the necessary management measures that can be taken in order to minimise resistance to antibiotics. Furthermore, the data help to decide on adequate therapy of E. coli infections of the intestinal tract in calves and pigs and encourage the responsible use of antibiotics in the interests of animal health and consumer protection.

  16. High-circulating leptin levels are associated with increased blood pressure in uncontrolled resistant hypertension.

    PubMed

    de Haro Moraes, C; Figueiredo, V N; de Faria, A P C; Barbaro, N R; Sabbatini, A R; Quinaglia, T; Ferreira-Melo, S E; Martins, L C; Demacq, C; Júnior, H M

    2013-04-01

    Leptin and aldosterone have been associated with the pathophysiological mechanisms of hypertension. However, despite studies showing the association of leptin with intima-media thickness, arterial distensibility and sympathetic nerve activation, the relationship between leptin and blood pressure (BP) in resistant hypertension (RHTN) is unknown. We aimed to assess the correlation of plasma leptin and aldosterone levels with BP in uncontrolled controlled RHTN (UCRHTN) and CRHTN patients. Plasma leptin and aldosterone levels, office BP, ambulatory BP monitoring and heart rate were measured in 41 UCRHTN, 39 CRHTN and 31 well-controlled HTN patients. No differences were observed between the three groups regarding gender, body mass index and age. The UCRHTN group had increased leptin when compared with CRHTN and well-controlled HTN patients (38.2±21.4, 19.6±8.7 and 20.94±13.9 ng ml(-1), respectively; P<0.05). Aldosterone levels values were also statistically different when comparing RHTN, CRHTN and well-controlled HTN patients (9.6±3.8, 8.1±5.0 and 8.0±4.7 ng dl(-1), respectively; P<0.05). As expected, UCRHTN patients had higher heart rate values compared with CRHTN and well-controlled HTN patients (86.2±7.2, 83.5±6.7 and 83.4±8.5, respectively; P<0.05). Plasma leptin positively correlated with systolic (SBP) and diastolic BP (DBP), and aldosterone (r=0.43, 0.35 and 0.47, respectively; all P<0.05) in UCRHTN, but neither in the CRHTN nor in the HTN group. Simple linear regression showed that SBP, DBP and aldosterone may be predicted by leptin (r(2)=0.16, 0.15 and 0.19, respectively; all P<0.05) only in the UCRHTN subgroup. In conclusion, UCRHTN patients have higher circulating leptin levels associated with increased plasma aldosterone and BP levels when compared with CRHTN and HTN subjects.

  17. Endogenous salicylic acid levels correlate with accumulation of pathogenesis-related proteins and virus resistance in tobacco

    SciTech Connect

    Yalpani, N.; Shulaev, V.; Raskin, I. )

    1993-07-01

    Salicylic acid (SA) is hypothesized to be an endogenous regulator of local and systemic disease resistance and an inducer of pathogenesis-related (PR) proteins among plants. High levels of PR proteins have been observed in an uninoculated amphidiploid hybrid of Nicotiana glutinosa [times] N. debneyi, which is highly resistant to tobacco mosaic virus (TMV). Fluoresence, UV, and mass spectral analysis established that the levels of SA in healthy N. glutinosa [times] N. debneyi leaves were 30 times greater than in N. tabacum [open quotes]Xanthi-nc[close quotes] tobacco, which does not constitutively express PR proteins and is less resistant to TMV. Upon TMV-inoculation SA levels increased at least 70-fold leaves of Xanthi-nc but role only slightly in the hybrid. Phloem exudates of N. glutinosa [times] N. debneyi contained at least 500 times more SA than those of Xanthi-nc. SA treatment caused the appearance of PR-1 protein in Xanthi-nc but did not affect constitutively high levels of PR-1 protein in N. glutinosa [times] N. debneyi. In contrast to Xanthi-nc tobacco, TMV-inoculated N. glutinosa [times] N. debneyi kept at 32 C accumulated more than 0.5 [mu]g SA/g fresh weight, maintained high levels of PR proteins, and developed a hypersensitive response to TMV. PR proteins have previously been shown to accumulate in the lower leaves of healthy, flowering Xanthi-nc tobacco, which exhibited increased resistance to TMV. These developmentally induced increases in resistance and PR-1 proteins positively correlated with tissue levels of SA. These results affirm the regulatory role of SA in disease resistance and PR protein production. 31 refs., 9 figs., 1 tab.

  18. Intermodulation and harmonic distortion in slow light Microwave Photonic phase shifters based on Coherent Population Oscillations in SOAs.

    PubMed

    Gasulla, Ivana; Sancho, Juan; Capmany, José; Lloret, Juan; Sales, Salvador

    2010-12-06

    We theoretically and experimentally evaluate the propagation, generation and amplification of signal, harmonic and intermodulation distortion terms inside a Semiconductor Optical Amplifier (SOA) under Coherent Population Oscillation (CPO) regime. For that purpose, we present a general optical field model, valid for any arbitrarily-spaced radiofrequency tones, which is necessary to correctly describe the operation of CPO based slow light Microwave Photonic phase shifters which comprise an electrooptic modulator and a SOA followed by an optical filter and supplements another recently published for true time delay operation based on the propagation of optical intensities. The phase shifter performance has been evaluated in terms of the nonlinear distortion up to 3rd order, for a modulating signal constituted of two tones, in function of the electrooptic modulator input RF power and the SOA input optical power, obtaining a very good agreement between theoretical and experimental results. A complete theoretical spectral analysis is also presented which shows that under small signal operation conditions, the 3rd order intermodulation products at 2Ω1 + Ω2 and 2Ω2 + Ω1 experience a power dip/phase transition characteristic of the fundamental tones phase shifting operation.

  19. Synthetic phase-shifting for optical testing: Point-diffraction interferometry without null optics or phase shifters

    PubMed Central

    Park, Ryeojin; Kim, Dae Wook; Barrett, Harrison H.

    2013-01-01

    An innovative iterative search method called the synthetic phase-shifting (SPS) algorithm is proposed. This search algorithm is used for maximum-likelihood (ML) estimation of a wavefront that is described by a finite set of Zernike Fringe polynomials. In this paper, we estimate the coefficient, or parameter, values of the wavefront using a single interferogram obtained from a point-diffraction interferometer (PDI). In order to find the estimates, we first calculate the squared-difference between the measured and simulated interferograms. Under certain assumptions, this squared-difference image can be treated as an interferogram showing the phase difference between the true wavefront deviation and simulated wavefront deviation. The wavefront deviation is the difference between the reference and the test wavefronts. We calculate the phase difference using a traditional phase-shifting technique without physical phase-shifters. We present a detailed forward model for the PDI interferogram, including the effect of the finite size of a detector pixel. The algorithm was validated with computational studies and its performance and constraints are discussed. A prototype PDI was built and the algorithm was also experimentally validated. A large wavefront deviation was successfully estimated without using null optics or physical phase-shifters. The experimental result shows that the proposed algorithm has great potential to provide an accurate tool for non-null testing. PMID:24216862

  20. High-Level Primary Clarithromycin Resistance of Helicobacter pylori in Algiers, Algeria: A Prospective Multicenter Molecular Study.

    PubMed

    Djennane-Hadibi, Fazia; Bachtarzi, Mohamed; Layaida, Karim; Ali Arous, Nassima; Nakmouche, Mhamed; Saadi, Berkane; Tazir, Mohamed; Ramdani-Bouguessa, Nadjia; Burucoa, Christophe

    2016-04-01

    Knowledge of local antibiotic resistance is crucial to adaptation for the choice of the optimal first-line treatment for Helicobacter pylori infection. Clarithromycin is a key component of the standard triple therapy largely used worldwide and, more particularly, in Algeria. Clarithromycin resistance is the main risk factor for treatment failure. The aim of this study was to evaluate, for the first time in Algeria, the prevalence of the primary resistance of H. pylori to clarithromycin. We conducted a prospective study (2008-2014) that included 195 Algerian patients referred for gastroduodenal endoscopy to two University Hospitals, one General Hospital, and several private gastroenterologists in Algiers (Algeria). One gastric biopsy was collected for the molecular detection of H. pylori and the mutations in 23S rRNA genes that confer resistance to clarithromycin with a quadruplex real-time PCR using Scorpion primers. The Scorpion PCR detected H. pylori DNA in 91 biopsies (47%). A mutation conferring resistance to clarithromycin was detected in 32 of the 91 positive patients (35%) and in 29 of the 88 positive patients never previously treated for an H. pylori infection (33%). The prevalence of primary resistance of H. pylori to clarithromycin was 33% in the Algerian population being studied. The high level of primary clarithromycin resistance in the H. pylori strains infecting the Algerian population that we report leads us to recommend the abandonment of the standard clarithromycin-based triple therapy as a first-line treatment in Algeria.

  1. Low alpha-synuclein levels in the blood are associated with insulin resistance

    PubMed Central

    Rodriguez-Araujo, Gerardo; Nakagami, Hironori; Takami, Yoichi; Katsuya, Tomohiro; Akasaka, Hiroshi; Saitoh, Shigeyuki; Shimamoto, Kazuaki; Morishita, Ryuichi; Rakugi, Hiromi; Kaneda, Yasufumi

    2015-01-01

    Mutations in the protein alpha-synuclein (SNCA) have been linked to Parkinson’s disease. We recently reported that non-mutated SNCA enhanced glucose uptake through the Gab1-PI3 kinase-Akt pathway and elucidated its effects on glucose regulation. Here, we examined the association of SNCA with insulin resistance (IR), a condition that is characterized by decreased tissue glucose uptake. Our observations include those from a population study as well as a SNCA-deficient mouse model, which had not previously been characterized in an IR scenario. In 1,152 patients, we found that serum SNCA levels were inversely correlated with IR indicators—body mass index, homeostatic model assessment for IR (HOMA-IR) and immunoreactive insulin (IRI)—and, to a lesser extent, with blood pressure and age. Additionally, SNCA-deficient mice displayed alterations in glucose and insulin responses during diet-induced IR. Moreover, during euglycemic clamp assessments, SNCA knock-out mice fed a high-fat diet (HFD) showed severe IR in adipose tissues and skeletal muscle. These findings provide new insights into IR and diabetes and point to SNCA as a potential candidate for further research. PMID:26159928

  2. Increased resistance to free radical damage induced by low-level sound conditioning.

    PubMed

    Harris, Kelly Carney; Bielefeld, Eric; Hu, Bo Hua; Henderson, Donald

    2006-03-01

    Conditioning is the phenomenon where exposure to moderate-level acoustic stimuli can increase the ear's resistance to subsequent more intense sound exposures. In recent years, research has shown that conditioning increases the availability of antioxidant enzymes which presumably protects the ear from oxidative stress induced by a traumatic noise exposure [Jacono, A.A., Hu, B., Kopke, R.D., Henderson, D., Van De Water, T.R., Steinman, H.M., 1998. Changes in cochlear antioxidant enzyme activity after sound conditioning and noise exposure in the chinchilla. Hear Res 117, 31-8]. The current study was designed to assess whether the increase in endogenous antioxidants seen following conditioning could provide protection from oxidative stress induced by Paraquat, a potent generator of superoxide. Chinchillas were exposed to a conditioning noise, 500 Hz OBN at 95 dB for 6 h/day for 10 days, followed 5 days later with Paraquat application to the round window. Controls underwent the Paraquat application surgery, without prior conditioning. Evoked potential thresholds were determined prior to conditioning, at day 1, 5 and 10 during conditioning, at day 15 (5 days after conditioning), and at day 17, 19, 23, and 35 (1, 3, 7, and 20 days post-Paraquat). The conditioned animals showed reductions in permanent threshold shift and reduced inner hair cell loss relative to controls. These results reinforce the hypothesis that antioxidants are primary mediators of the conditioning effect.

  3. Resistance to sliding of stainless steel multistranded archwires and comparison with single-stranded leveling wires.

    PubMed

    Rucker, Brian K; Kusy, Robert P

    2002-07-01

    The sliding mechanics of multistranded stainless steel (SS) wires were compared with single-stranded leveling wires in the passive and the active regions when dominated by classical friction and elastic binding, respectively. Tests were done under both dry and wet (human saliva) conditions. The round multistranded wires had 3- (triple) and 6-stranded (coax) configurations in nominal sizes of 15.5, 17.5, 19.5, and 21.5 mil; the rectangular wires had 3- (rect3) and 8-stranded (rect8) configurations in nominal sizes of 16 x 16, 16 x 22, 17 x 25, and 19 x 25 mil. While a ligature force of 150 g was applied and the second-order angulation was varied from -12 degrees to 12 degrees, each wire was translated relative to its bracket as the drawing force was digitally recorded. Linear regressions were fitted separately to the passive and the active regions. In the passive region, the kinetic coefficients of friction mu(k-FR) in the wet state were the same as, lower than, and higher than in the dry state for single-stranded SS, single-stranded nickel titanium (NiTi), and multistranded SS wires, respectively. Because the kinetic coefficients of friction were similar for multistranded and single-stranded SS wires, mu(k-FR) is a material property for SS and perhaps also for NiTi. In the active region, the frictional behaviors of multistranded SS wires compared with other leveling archwires are as follows: (1) coax wires had low friction, (2) triple and rect8 wires had midrange friction, and (3) rect3 wires had high friction. The coefficients of binding (mu(BI)) were not affected by saliva and were proportional to the wire stiffnesses. The resistance to sliding depended on wire stiffnesses to the extent that the differences in the mu(k-FR)'s of SS versus NiTi became unimportant shortly after binding occurred.

  4. Effect of grip type, wrist motion, and resistance level on pressures within the carpal tunnel of normal wrists.

    PubMed

    McGorry, Raymond W; Fallentin, Nils; Andersen, Johan H; Keir, Peter J; Hansen, Torben B; Pransky, Glenn; Lin, Jia-Hua

    2014-04-01

    Elevated carpal tunnel pressure (CTP) has been associated with carpal tunnel syndrome. This study systematically evaluated the effect of wrist motion resistance and grip type on CTP during wrist motion typical of occupational tasks. CTP during four wrist motion patterns, with and without resistance, and with and without gripping, was measured in vivo in 14 healthy individuals. CTP measured during compound motions fell between that measured in the cardinal planes of wrist flexion/extension and radial/ulnar deviation. Generally, with no active gripping there was little pressure change due to wrist angular displacement or resistance level. However, concurrent active pinch or power grip increased CTP particularly in motions including extension. CTP typically did not increase during wrist flexion, and in fact often decreased. Extension motions against resistance when employing a pinch or power grip increase CTP more than motions with flexion. Results could help inform design or modification of wrist motion intensive occupational tasks. © 2014 The Authors.

  5. Evolution of high-level, multiple anthelmintic resistance on a sheep farm in Malaysia.

    PubMed

    Chandrawathani, P; Waller, P J; Adnan, M; Höglund, J

    2003-02-01

    Anthelmintic resistance in nematode parasites of sheep and goats on a government farm in north Malaysia was monitored over a 3-year period (1997-2000). The faecal egg count reduction test (FECRT) was conducted on young sheep at the beginning and end of this period. Changes in management, designed to reduce the selection pressure for the development of anthelmintic resistance, were also implemented during this time. By far the most important parasite problem was Haemonchus contortus. In 1997, this nematode was found to be resistant to levamisole, with suspected resistance to closantel and moxidectin. However, when the FECRT was repeated 3 years later, its resistance status had become much more severe, with resistance to benzimidazole, levamisole and ivermectin, and suspected resistance to moxidectin. This rapid evolution to multiple anthelmintic resistance is a major concern that needs to be arrested. There is an urgent need to evaluate other control strategies that incorporate livestock management, the 'smart' use of drugs and non-chemotherapeutic approaches, such as biological control agents.

  6. High level multiple antibiotic resistance among fish surface associated bacterial populations in non-aquaculture freshwater environment.

    PubMed

    Ozaktas, Tugba; Taskin, Bilgin; Gozen, Ayse G

    2012-12-01

    Freshwater fish, Alburnus alburnus (bleak), were captured from Lake Mogan, situated in Ankara, during spring. The surface mucus of the fish was collected and associated bacteria were cultured and isolated. By sequencing PCR-amplified 16S RNA encoding genes, the isolates were identified as members of 12 different genera: Acinetobacter, Aeromonas, Bacillus, Brevundimonas, Gordonia, Kocuria, Microbacterium, Mycobacterium, Pseudomonas, Rhodococcus, and Staphylococcus, in addition to one strain that was unidentified. The mucus-dwelling bacterial isolates were tested for resistance against ampicillin, kanamycin, streptomycin and chloramphenicol. About 95% of the isolates were found to be resistant to ampicillin, 93% to chloramphenicol, and 88% to kanamycin and streptomycin. A Microbacterium oxydans and the unidentified environmental isolate were resistant to all four antibiotics tested at very high levels (>1600 μg/ml ampicillin and streptomycin; >1120 μg/ml kanamycin; >960 μg/ml chloramphenicol). Only a Kocuria sp. was sensitive to all four antibiotics at the lowest concentrations tested (3.10 μg/ml ampicillin and streptomycin; 2.15 μg/ml kanamycin; 1.85 μg/ml chloramphenicol). The rest of the isolates showed different resistance levels. Plasmid isolations were carried out to determine if the multiple antibiotic resistance could be attributed to the presence of plasmids. However, no plasmid was detected in any of the isolates. The resistance appeared to be mediated by chromosome-associated functions. This study indicated that multiple antibiotic resistance at moderate to high levels is common among the current phenotypes of the fish mucus-dwelling bacterial populations in this temperate, shallow lake which has not been subjected to any aquaculturing so far but under anthropogenic effect being in a recreational area.

  7. Alarming Levels of Drug-Resistant Tuberculosis in HIV-Infected Patients in Metropolitan Mumbai, India

    PubMed Central

    Isaakidis, Petros; Das, Mrinalini; Kumar, Ajay M V; Peskett, Christopher; Khetarpal, Minni; Bamne, Arun; Adsul, Balkrishna; Manglani, Mamta; Sachdeva, Kuldeep Singh; Parmar, Malik; Kanchar, Avinash; Rewari, B.B.; Deshpande, Alaka; Rodrigues, Camilla; Shetty, Anjali; Rebello, Lorraine; Saranchuk, Peter

    2014-01-01

    Background Drug-resistant tuberculosis (DR-TB) is a looming threat to tuberculosis control in India. However, no countrywide prevalence data are available. The burden of DR-TB in HIV-co-infected patients is likewise unknown. Undiagnosed and untreated DR-TB among HIV-infected patients is a major cause of mortality and morbidity. We aimed to assess the prevalence of DR-TB (defined as resistance to any anti-TB drug) in patients attending public antiretroviral treatment (ART) centers in greater metropolitan Mumbai, India. Methods A cross-sectional survey was conducted among adults and children ART-center attendees. Smear microscopy, culture and drug-susceptibility-testing (DST) against all first and second-line TB-drugs using phenotypic liquid culture (MGIT) were conducted on all presumptive tuberculosis patients. Analyses were performed to determine DR-TB prevalence and resistance patterns separately for new and previously treated, culture-positive TB-cases. Results Between March 2013 and January 2014, ART-center attendees were screened during 14135 visits, of whom 1724 had presumptive TB. Of 1724 attendees, 72 (4%) were smear-positive and 202 (12%) had a positive culture for Mycobacterium tuberculosis. Overall DR-TB was diagnosed in 68 (34%, 95% CI: 27%–40%) TB-patients. The proportions of DR-TB were 25% (29/114) and 44% (39/88) among new and previously treated cases respectively. The patterns of DR-TB were: 21% mono-resistant, 12% poly-resistant, 38% multidrug-resistant (MDR-TB), 21% pre-extensively-drug-resistant (MDR-TB plus resistance to either a fluoroquinolone or second-line injectable), 6% extensively drug-resistant (XDR-TB) and 2% extremely drug-resistant TB (XDR-TB plus resistance to any group-IV/V drug). Only previous history of TB was significantly associated with the diagnosis of DR-TB in multivariate models. Conclusion The burden of DR-TB among HIV-infected patients attending public ART-centers in Mumbai was alarmingly high, likely representing ongoing

  8. Relationship between biomass production and nitrogen fixation under drought stress conditions in peanut genoytpes with different levels of drought resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The relationship between biomass production and N2 fixation under drought stress conditions in peanut genotypes with different levels of drought resistance is not well understood. The objective of this study was to determine the effect of drought on biomass production and N2 fixation by evaluating t...

  9. Relations between Children's Levels of Responsiveness and Resistance, Maternal Interaction Behaviors, and Children's Social Behaviors with Peers in School

    ERIC Educational Resources Information Center

    Salinas, Daniela; Neitzel, Carin

    2017-01-01

    Children's peer relationships have their origins in family relationships. The present study focuses on the relative importance of children's levels of responsiveness and/or resistance during mother-child interactions and tests a model of the direct and indirect relations between mother interaction behaviors and children's social behaviors with…

  10. New in vitro tests to evaluate the resistance level of the cattle tick, Rhipicephalus (Boophilus) microplus, against acaricides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of the present study was to compare two new in vitro tests designed to evaluate the resistance level of R. microplus with two tests currently recommended by the Food and Agriculture Organization of the United Nations (FAO): one performed on larvae, the Larval Packet Test (LPT) and one ...

  11. Critical role of androgen receptor level in prostate cancer cell resistance to new generation antiandrogen enzalutamide

    PubMed Central

    Hoefer, Julia; Akbor, Mohammady; Handle, Florian; Ofer, Philipp; Puhr, Martin; Parson, Walther; Culig, Zoran; Klocker, Helmut; Heidegger, Isabel

    2016-01-01

    Enzalutamide is an androgen receptor (AR) inhibitor approved for therapy of metastatic castration resistant prostate cancer. However, clinical application revealed that 30 to 40% of patients acquire resistance after a short period of treatment. Currently, the molecular mechanisms underlying such resistances are not completely understood, partly due to a lack of model systems. In the present study we established three different cellular models of enzalutamide resistance including a cell line with wild type AR (LAPC4), DuCaP cells which overexpress wild-type AR, as well as a cell which has been adapted to long term androgen ablation (LNCaP Abl) and harbors the AR T878A mutation. After 10 months of cultivation, sustained growth in the presence of enzalutamide was achieved. When compared to controls, resistant cells exhibit significantly decreased sensitivity to enzalutamide as measured with 3[H]thymidine incorporation and WST assay. Moreover, these cell models exhibit partly re-activated AR signaling despite presence of enzalutamide. In addition, we show that enzalutamide resistant cells are insensitive to bicalutamide but retain considerable sensitivity to abiraterone. Mechanistically, enzalutamide resistance was accompanied by increased AR and AR-V7 mRNA and protein expression as well as AR gene amplification, while no additional AR mutations have been identified. PMID:27486973

  12. Critical role of androgen receptor level in prostate cancer cell resistance to new generation antiandrogen enzalutamide.

    PubMed

    Hoefer, Julia; Akbor, Mohammady; Handle, Florian; Ofer, Philipp; Puhr, Martin; Parson, Walther; Culig, Zoran; Klocker, Helmut; Heidegger, Isabel

    2016-09-13

    Enzalutamide is an androgen receptor (AR) inhibitor approved for therapy of metastatic castration resistant prostate cancer. However, clinical application revealed that 30 to 40% of patients acquire resistance after a short period of treatment. Currently, the molecular mechanisms underlying such resistances are not completely understood, partly due to a lack of model systems. In the present study we established three different cellular models of enzalutamide resistance including a cell line with wild type AR (LAPC4), DuCaP cells which overexpress wild-type AR, as well as a cell which has been adapted to long term androgen ablation (LNCaP Abl) and harbors the AR T878A mutation. After 10 months of cultivation, sustained growth in the presence of enzalutamide was achieved. When compared to controls, resistant cells exhibit significantly decreased sensitivity to enzalutamide as measured with 3[H]thymidine incorporation and WST assay. Moreover, these cell models exhibit partly re-activated AR signaling despite presence of enzalutamide. In addition, we show that enzalutamide resistant cells are insensitive to bicalutamide but retain considerable sensitivity to abiraterone. Mechanistically, enzalutamide resistance was accompanied by increased AR and AR-V7 mRNA and protein expression as well as AR gene amplification, while no additional AR mutations have been identified.

  13. Moderate Levels of Pre-Treatment HIV-1 Antiretroviral Drug Resistance Detected in the First South African National Survey

    PubMed Central

    Steegen, Kim; Carmona, Sergio; Bronze, Michelle; Papathanasopoulos, Maria A.; van Zyl, Gert; Goedhals, Dominique; MacLeod, William; Sanne, Ian; Stevens, Wendy S.

    2016-01-01

    Background In order to assess the level of transmitted and/or pre-treatment antiretroviral drug resistance to HIV-1, the World Health Organization (WHO) recommends that regular surveys are conducted. This study’s objective was to assess the frequency of HIV-1 antiretroviral drug resistance in patients initiating antiretroviral treatment (ART) in the public sector throughout South Africa. Methods A prospective cross-sectional survey was conducted using probability proportional to size sampling. This method ensured that samples from each province were proportionally collected, based on the number of patients receiving ART in each region. Samples were collected between March 2013 and October 2014. Pol sequences were obtained using RT-PCR and Sanger sequencing and submitted to the Stanford Calibrated Population Resistance tool v6.0. Results A total of 277 sequences were available for analysis. Most participants were female (58.8%) and the median age was 34 years (IQR: 29–42). The median baseline CD4-count was 149 cells/mm3 (IQR: 62–249) and, based on self-reporting, participants had been diagnosed as HIV-positive approximately 44 days prior to sample collection (IQR: 23–179). Subtyping revealed that 98.2% were infected with HIV-1 subtype C. Overall, 25 out of 277 patients presented with ≥1 surveillance drug resistance mutation (SDRM, 9.0%, 95% CI: 6.1–13.0%). Non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations were the most numerous mutations detected (n = 23). Only two patients presented with a protease inhibitor (PI) mutation. In four patients ≥4 SDRMs were detected, which might indicate that these patients were not truly ART-naïve or were infected with a multi-resistant virus. Conclusions These results show that the level of antiretroviral drug resistance in ART-naïve South Africans has reached moderate levels, as per the WHO classification. Therefore, regular surveys of pre-treatment drug resistance levels in all regions of South Africa

  14. Investigation of the reformulated Remel Synergy Quad plate for detection of high-level aminoglycoside and vancomycin resistance among enterococci.

    PubMed

    Free, L; Sahm, D F

    1995-06-01

    We investigated the accuracy of the recently released Remel Synergy Quad plate, a commercially available agar screening method for detecting high-level aminoglycoside and vancomycin resistance among enterococci that is based on the National Committee for Clinical Laboratory Standards recommended guidelines (National Committee for Clinical Laboratory Standards, M7-A3, 1993). The Synergy Quad correctly determined the gentamicin and streptomycin resistance status for > or = 97% of 147 Enterococcus faecalis and Enterococcus faecium isolates tested. Detection of vancomycin resistance also was reliable, as no false susceptibility occurred with 36 vancomycin-resistant E. faecalis and E. faecium strains and false resistance occurred only once with the 47 susceptible strains tested. One strain each of Enterococcus gallinarum and Enterococcus casseliflavus failed to grow on the screen, but because the true nature and significance of resistance in such isolates is unknown the implication of their screen negativity is uncertain. In summary, the Remel Synergy Quad provides a highly accurate and convenient method for susceptibility testing of enterococci against gentamicin, streptomycin, and vancomycin.

  15. Dynamic Gain Equalizer Using Hybrid Integrated Silica-Based Planar Lightwave Circuits With LiNbO3 Phase Shifter Array

    NASA Astrophysics Data System (ADS)

    Maru, Koichi; Chiba, Takafumi; Tanaka, Kotaro; Himi, Susumu; Uetsuka, Hisato

    2006-01-01

    This paper proposes a dynamic gain equalizer (DGE) using hybrid integrated silica-based planar lightwave circuits (PLCs) with a LiNbO3 (LN) phase shifter array to achieve a DGE that offers both excellent optical performance and control of the phase shifters. The structure consists of two PLCs having arrayed-waveguide gratings (AWGs) and couplers directly attached to the LN phase shifter array at its end faces. To reduce polarization-dependent characteristics, a polarization diversity technique using a polarization beam splitter (PBS) and a circulator was employed. To reduce polarization-dependent loss (PDL) due to the reflected light at the PLC-LN interfaces, tilted waveguides from the normal direction to the interfaces were introduced, and the relation between PDL and power reflectivity was theoretically investigated. A hybrid integrated DGE using super-high-Delta PLCs and a 25-channel electrooptic (EO) phase shifter array was demonstrated. The PDL was effectively suppressed with the introduced polarization diversity technique, and the measured spectra were in good agreement with designed profiles. These results indicate that the proposed hybrid integrated DGE offers good performance and controllability for practical applications.

  16. Shielding Effects of a Building Structure on the Energy Deposit of Cosmic Rays in a Simple Wavelength Shifter-Based Scintillator

    ERIC Educational Resources Information Center

    Aiola, Salvatore; La Rocca, Paola; Riggi, Francesco; Riggi, Simone

    2012-01-01

    An experimental setup, based on a plastic scintillator with an embedded wavelength shifter fibre and photosensors at the two ends, has been used to detect cosmic muons in undergraduate laboratory activities. Time and amplitude information from the two photosensors were measured using the time-over-threshold technique. The distribution of the…

  17. High-level amikacin resistance in Escherichia coli due to phosphorylation and impaired aminoglycoside uptake.

    PubMed Central

    Perlin, M H; Lerner, S A

    1986-01-01

    Plasmid pMP1-1 in Escherichia coli L-0 encodes aminoglycoside (AG) 3'-phosphotransferase II [APH(3')-II]. This enzyme modifies and confers high-level resistance to kanamycin. Although amikacin is a substrate for APH(3')-II, strain L-0(pMP1-1) is susceptible to amikacin. Plasmid pMP1-2 is a spontaneous mutant of pMP1-1 which determines increased APH(3')-II activity for amikacin, apparently as a result of an increase in the copy number of the plasmid. From amikacin-susceptible, gentamicin-susceptible transformants and transconjugants that bear the APH(3')-II gene on plasmid pMP1-1 or pMP1-2 or cloned into multicopy plasmid pBR322, we selected spontaneous mutants at concentrations of amikacin or gentamicin that were two to four times higher than the MICs of these antibiotics. In each case, whether they were selected by using amikacin or gentamicin, the mutants exhibited modest (two- to eightfold) increases in the MIC of gentamicin and major (64- to 128-fold) increases in the MIC of amikacin. Using these laboratory strains of E. coli, we examined the effects on AG susceptibility of the interaction of AG-modifying enzyme activity and generalized AG uptake. Increasing the level of activity of an AG phosphotransferase in these strains lowered their susceptibility to AGs which were substrates for which the enzyme had low Kms. However, an increase in AG-modifying activity alone did not result in large increases in the MICs for poor substrates of the enzyme. In strains which lacked AG-modifying enzymes, a decrease in the rate of AG uptake increased the MICs modestly for a broad spectrum of AGs. When a strain bore the phosphotransferase, a decrease in generalized AG uptake could raise the MIC further, not only for low-Km substrates, but even for AG substrates for which the enzyme had high Kms. Thus, increased modifying activity, together with a diminished rate of uptake, could produce even higher MICs for poor AG substrates. PMID:2424366

  18. Increased Serum Levels of Oxytocin in ‘Treatment Resistant Depression in Adolescents (TRDIA)’ Group

    PubMed Central

    Hashimoto, Kenji; Oda, Yasunori; Ishima, Tamaki; Yakita, Madoka; Kurata, Tsutomu; Kunou, Masaru; Takahashi, Jumpei; Kamata, Yu; Kimura, Atsushi; Niitsu, Tomihisa; Komatsu, Hideki; Hasegawa, Tadashi; Shiina, Akihiro; Hashimoto, Tasuku; Kanahara, Nobuhisa; Shimizu, Eiji; Iyo, Masaomi

    2016-01-01

    Objective ‘Treatment-resistant depression’ is depression that does not respond to an adequate regimen of evidence-based treatment. Treatment-resistant depression frequently becomes chronic. Children with treatment-resistant depression might also develop bipolar disorder (BD). The objective of this study was to determine whether serum levels of oxytocin (OXT) in treatment-resistant depression in adolescents (TRDIA) differ from non-treatment-resistant depression in adolescents (non-TRDIA) or controls. We also investigated the relationships between serum OXT levels and the clinical symptoms, severity, and familial histories of adolescent depressive patients. Methods We measured serum OXT levels: TRDIA (n = 10), non-TRDIA (n = 27), and age- and sex- matched, neurotypical controls (n = 25). Patients were evaluated using the Children’s Depression Rating Scale-Revised (CDRS-R) and the Depression Self-Rating Scale for Children-Japanese Version (DSRS-C-J). The patients were also assessed retrospectively using the following variables: familial history of major depressive disorder and BD (1st degree or 2nd degree), history of disruptive mood dysregulation disorder, recurrent depressive disorder (RDD), history of antidepressant activation. Results Serum levels of OXT among the TRDIA and non-TRDIA patients and controls differed significantly. Interestingly, the rates of a family history of BD (1st or 2nd degree), RDD and a history of antidepressant activation in our TRDIA group were significantly higher than those of the non-TRDIA group. Conclusions Serum levels of OXT may play a role in the pathophysiology of TRDIA. PMID:27536785

  19. Urban-rural differences explain the association between serum 25-hydroxyvitamin D level and insulin resistance in Korea.

    PubMed

    Song, Bo Mi; Rhee, Yumie; Kim, Chang Oh; Youm, Yoosik; Kim, Kyoung Min; Lee, Eun Young; Lee, Ju-Mi; Yoon, Young Mi; Kim, Hyeon Chang

    2014-12-11

    An increasing number of studies report associations between low serum 25-hydroxyvitamin D [25(OH)D] level and insulin resistance; however, whether low vitamin D levels directly contribute to increased insulin resistance is unclear. We investigated the impact of residential area on the association between 25(OH)D and insulin resistance in elderly Koreans. Using data from the Korean Urban Rural Elderly study, we conducted cross-sectional analyses in 1628 participants (505 men and 1123 women). Serum 25(OH)D was analyzed as both continuous and categorized variables. Homeostasis model assessment for insulin resistance (HOMA-IR) was calculated using fasting blood glucose and insulin levels. In men, 25(OH)D level was inversely associated with HOMA-IR (standardized β = -0.133, p < 0.001) after adjustment for age, body mass index, waist circumference, smoking, alcohol intake, exercise, and study year. However, we noted significant urban-rural differences in 25(OH)D level (43.4 versus 65.6 nmol/L; p < 0.001) and HOMA-IR (1.2 versus 0.8 mmol · pmol/L2; p < 0.001). When we additionally adjusted for residential area, the association between 25(OH)D and HOMA-IR was attenuated (standardized β = -0.063, p = 0.115). In women, the association between 25(OH)D and HOMA-IR was not significant before or after adjustment for residential area. Environmental or lifestyle differences in urban and rural areas may largely explain the inverse association between serum 25(OH)D and insulin resistance.

  20. High-level Multi-Resistant and Virulent Escherichia coli in Abeokuta, Nigeria.

    PubMed

    Akinduti, Paul Akinniyi; Aboderin, Bukola W; Oloyede, Rasaq; Ogiogwa, Joseph I; Motayo, Babatunde O; Ejilude, Oluwaseun

    2016-01-01

    Multi-resistant Escherichia coli (E. coli) strains co-harboring virulence genes is a cause of high morbidity in Abeokuta, Nigeria. This study was designed to determine some virulent factors among enteropathogenic E. coli in Abeokuta, Nigeria. Approximately non-repetitive 102 isolates of E. coli were recovered from clinical samples from two health facilities in Abeokuta. Biotyping using API and antibiotic susceptibility was determined, and eae and flic genes were assayed by PCR. Antibiotic resistance relatedness was performed by DendroUPGMA. Results showed that 48.0% and 52.0 % were intestinal and extra-intestinal E. coli, ampicillin recorded 100% resistance, amoxycilli/clavulanic acid 64.7%, cotrimoxazole 57.8% and 56.8% resistance against cefotaxime, at MIC >16 ug/mL, 100%, 57.8%, and 50% have MIC50 to ampicillin, tetracycline, and ceftazidime, while 74.5% and 48.0% have MIC90 to ampicillin and ceftazidime. Significant rates of 4.9%, 7.8%, and 9.8% flic, eae, and flic/eae genes were found in intestinal isolates, while 2.9%, 2.0%, and 3.9% were found in extra-intestinal (P < 0.05). Two major clades of the resistant isolates reveal significant antibiotic relatedness among intestinal and extra-intestinal isolates, at 54% resistance similarities with very high multi-antibiotic resistance index of 1.0 (MARI). A high rate of undetected virulent E. coli pathotypes with high resistance could trigger unprecedented morbidity and mortality, mostly among children and the elderly.

  1. Novel Plasmids and Resistance Phenotypes in Yersinia pestis: Unique Plasmid Inventory of Strain Java 9 Mediates High Levels of Arsenic Resistance

    PubMed Central

    Eppinger, Mark; Radnedge, Lyndsay; Andersen, Gary; Vietri, Nicholas; Severson, Grant; Mou, Sherry; Ravel, Jacques; Worsham, Patricia L.

    2012-01-01

    Growing evidence suggests that the plasmid repertoire of Yersinia pestis is not restricted to the three classical virulence plasmids. The Java 9 strain of Y. pestis is a biovar Orientalis isolate obtained from a rat in Indonesia. Although it lacks the Y. pestis-specific plasmid pMT, which encodes the F1 capsule, it retains virulence in mouse and non-human primate animal models. While comparing diverse Y. pestis strains using subtractive hybridization, we identified sequences in Java 9 that were homologous to a Y. enterocolitica strain carrying the transposon Tn2502, which is known to encode arsenic resistance. Here we demonstrate that Java 9 exhibits high levels of arsenic and arsenite resistance mediated by a novel promiscuous class II transposon, named Tn2503. Arsenic resistance was self-transmissible from Java 9 to other Y. pestis strains via conjugation. Genomic analysis of the atypical plasmid inventory of Java 9 identified pCD and pPCP plasmids of atypical size and two previously uncharacterized cryptic plasmids. Unlike the Tn2502-mediated arsenic resistance encoded on the Y. enterocolitica virulence plasmid; the resistance loci in Java 9 are found on all four indigenous plasmids, including the two novel cryptic plasmids. This unique mobilome introduces more than 105 genes into the species gene pool. The majority of these are encoded by the two entirely novel self-transmissible plasmids, which show partial homology and synteny to other enterics. In contrast to the reductive evolution in Y. pestis, this study underlines the major impact of a dynamic mobilome and lateral acquisition in the genome evolution of the plague bacterium. PMID:22479347

  2. Studies of Corrosion Resistant Materials Being Considered for High-Level Nuclear Waste Containment in Yucca Mountain Relevant Environments

    SciTech Connect

    McCright, R.D.; Ilevbare, G.; Estill, J.; Rebak, R.

    2001-12-09

    Containment of spent nuclear fuel and vitrified forms of high level nuclear waste require use of materials that are highly corrosion resistant to all of the anticipated environmental scenarios that can occur in a geological repository. Ni-Cr-Mo Alloy 22 (UNS N60622) is proposed for the corrosion resistant outer barrier of a two-layer waste package container at the potential repository site at Yucca Mountain. A range of water compositions that may contact the outer barrier is under consideration, and a testing program is underway to characterize the forms of corrosion and to quantify the corrosion rates. Results from the testing support models for long term prediction of the performance of the container. Results obtained to date indicate a very low general corrosion rate for Alloy 22 and very high resistance to all forms of localized and environmentally assisted cracking in environments tested to date.

  3. Origins of low resistivity and Ge donor level in Ge ion-implanted ZnO bulk single crystals

    SciTech Connect

    Kamioka, K.; Oga, T.; Izawa, Y.; Kuriyama, K.; Kushida, K.

    2013-12-04

    The energy level of Ge in Ge-ion implanted ZnO single crystals is studied by Hall-effect and photoluminescence (PL) methods. The variations in resistivity from ∼10{sup 3} Ωcm for un-implanted samples to ∼10{sup −2} Ωcm for as-implanted ones are observed. The resistivity is further decreased to ∼10{sup −3} Ωcm by annealing. The origins of the low resistivity are attributed to both the zinc interstitial (Zn{sub i}) related defects and the electrical activated Ge donor. An activation energy of Ge donors estimated from the temperature dependence of carrier concentration is 102 meV. In PL studies, the new peak at 372 nm (3.33 eV) related to the Ge donor is observed in 1000 °C annealed samples.

  4. Alarming levels of drug-resistant tuberculosis in Belarus: results of a survey in Minsk.

    PubMed

    Skrahina, Alena; Hurevich, Henadz; Zalutskaya, Aksana; Sahalchyk, Evgeni; Astrauko, Andrei; van Gemert, Wayne; Hoffner, Sven; Rusovich, Valiantsin; Zignol, Matteo

    2012-06-01

    Resistance to anti-tuberculosis (TB) medicines is a major public health threat in most countries of the former Soviet Union. As no representative and quality-assured information on the magnitude of this problem existed in Belarus, a survey was conducted in the capital city of Minsk. Between November 2009 and December 2010, 156 consecutively diagnosed new and 68 previously treated culture-positive TB patients residing in Minsk were enrolled in the survey. Mycobacterium tuberculosis isolates were obtained from each patient and tested for susceptibility to first- and second-line anti-TB drugs. Multidrug-resistant (MDR)-TB was found in 35.3% (95% CI 27.7-42.8) of new patients and 76.5% (95% CI 66.1-86.8) of those previously treated. Overall, nearly one in two patients enrolled had MDR-TB. Extensively drug-resistant TB was reported in 15 of the 107 MDR-TB patients (14.0%, 95% CI 7.3-20.7). Patients <35 yrs of age have shown a two times higher odds ratio of multidrug-resistant TB than those aged >35 yrs. The findings of this survey in Minsk city are alarming and represent the highest proportions of MDR-TB ever recorded in the world. This study greatly contributes to the understanding of the burden of drug-resistant TB in urban areas of Belarus.

  5. Solar pumped Nd:YAG laser efficiency enhancement using Cr:LiCAF frequency down-shifter

    NASA Astrophysics Data System (ADS)

    Payziyev, Sh.; Makhmudov, Kh.

    2016-12-01

    The possibility of increase of Nd:YAG solar pumped lasers pumping efficiency with the use of Cr:LiCAF as a solar spectrum frequency-down-shifting element is studied by the simulation calculation method. Comparative analyses of side- and end-pumping schemes are conducted. The numerical experiments have been conducted for combinations of Nd:YAG active medium and Cr:LiCAF for both side- and end-pumping configurations. It is shown that the use of Cr:LiCAF frequency down-shifter significantly increases the pumping efficiency of Nd:YAG active medium in both cases. In addition the replacement of Nd:YAG with cerium co-doped Nd:YAG have shown possibility of further increase the efficiency.

  6. High figure-of-merit compact phase shifters based on liquid crystal material for 1-10 GHz applications

    NASA Astrophysics Data System (ADS)

    Cai, Longzhu; Xu, Huan; Li, Jinfeng; Chu, Daping

    2017-01-01

    A liquid crystal (LC) based tunable microstrip line (ML) phase shifter featuring high performance is presented. The experimental results show an electrically tunable differential phase up to 360° at 10 GHz with an overall insertion loss <8.5 dB. The device possesses a high figure-of-merit (FoM) of 64°/dB at 9.8 GHz and 60°/dB between 7-10 GHz. This is achieved by simultaneously considering both of the LC tuned phase and overall loss in the design. The proposed device utilizes the inverted meander ML technology to minimize its size. Taking into account the real fabrication procedure, a novel impedance matching structure is applied, and the measured return loss is considerably improved. The FoM and phase tuning property of the fabricated device as optimized are compared with the state-of-art results published recently and show better performance for both of them.

  7. A gallium-arsenide digital phase shifter for clock and control signal distribution in high-speed digital systems

    NASA Technical Reports Server (NTRS)

    Fouts, Douglas J.

    1992-01-01

    The design, implementation, testing, and applications of a gallium-arsenide digital phase shifter and fan-out buffer are described. The integrated circuit provides a method for adjusting the phase of high-speed clock and control signals in digital systems, without the need for pruning cables, multiplexing between cables of different lengths, delay lines, or similar techniques. The phase of signals distributed with the described chip can be dynamically adjusted in eight different steps of approximately 60 ps per step. The IC also serves as a fan-out buffer and provides 12 in-phase outputs. The chip is useful for distributing high-speed clock and control signals in synchronous digital systems, especially if components are distributed over a large physical area or if there is a large number of components.

  8. Design of a vector-sum integrated microwave photonic phase shifter in silicon-on-insulator waveguides.

    PubMed

    Qu, Pengfei; Liu, Caixia; Dong, Wei; Chen, Weiyou; Li, Fumin; Li, Haibin; Gong, Zhaoxin; Ruan, Shengping; Zhang, Xindong; Zhou, Jingran

    2011-06-10

    An orthogonal vector-sum integrated microwave photonic phase shifter (IMWPPS), consisting of mode-order converter multiplexers (MOCMs), a variable optical power splitter (VOPS), an optical switch (OS) and fixed time delay lines (FTDLs), was theoretically demonstrated in a silicon-on-insulator wafer. MOCMs, as a key element of our device, were employed to generate orthogonal vector signals and served as lossless optical combiners. Combining with the thermo-optical VOPS, OS and FTDLs, the microwave phase shift of 0∼2π could be achieved by a refractive index variation of 0∼15×10(-3) in the millimeter wave band. The corresponding tuning resolution was about 1.64°/°C. This work, for the first time to our knowledge, provides an attractive solution to transferring a vector-sum method based bulk MWPPS into a integrated one, which is very important for large-scale optically controlled phase array antenna.

  9. Performance analysis of the dual-parallel polarization modulator based optical single-sideband modulator/frequency shifter

    NASA Astrophysics Data System (ADS)

    Li, Xiaofan; Li, Jianping; Li, Zhaohui

    2016-06-01

    The performance of the dual-parallel polarization modulator based optical single-sideband modulator (PSSBM) or frequency shifter (FS) has been studied theoretically. There are various factors impacting the performance of PSSBM/FS, such as the state of polarization (SOP), imbalanced power ratio, and direct current (dc) bias control, and they all have been validated through the VPI software. Based on our simulation results, the desired high-quality SSB frequency shift can be achieved through the PSSBM/FS by applying the optimized parameters while only one dc bias control is required. The results show that PSSBM/FS has the advantages and potentiality to be a commercial product used in various scenarios.

  10. Vip3A Resistance Alleles Exist at High Levels in Australian Targets before Release of Cotton Expressing This Toxin

    PubMed Central

    Mahon, Rod J.; Downes, Sharon J.; James, Bill

    2012-01-01

    Crops engineered to produce insecticidal crystal (Cry) proteins from the soil bacterium Bacillus thuringiensis (Bt) have revolutionised pest control in agriculture. However field-level resistance to Bt has developed in some targets. Utilising novel vegetative insecticidal proteins (Vips), also derived from Bt but genetically distinct from Cry toxins, is a possible solution that biotechnical companies intend to employ. Using data collected over two seasons we determined that, before deployment of Vip-expressing plants in Australia, resistance alleles exist in key targets as polymorphisms at frequencies of 0.027 (n = 273 lines, 95% CI = 0.019–0.038) in H. armigera and 0.008 (n = 248 lines, 0.004–0.015) in H. punctigera. These frequencies are above mutation rates normally encountered. Homozygous resistant neonates survived doses of Vip3A higher than those estimated in field-grown plants. Fortunately the resistance is largely, if not completely, recessive and does not confer resistance to the Bt toxins Cry1Ac or Cry2Ab already deployed in cotton crops. These later characteristics are favourable for resistance management; however the robustness of Vip3A inclusive varieties will depend on resistance frequencies to the Cry toxins when it is released (anticipated 2016) and the efficacy of Vip3A throughout the season. It is appropriate to pre-emptively screen key targets of Bt crops elsewhere, especially those such as H. zea in the USA, which is not only closely related to H. armigera but also will be exposed to Vip in several varieties of cotton and corn. PMID:22761737

  11. Vip3A resistance alleles exist at high levels in Australian targets before release of cotton expressing this toxin.

    PubMed

    Mahon, Rod J; Downes, Sharon J; James, Bill

    2012-01-01

    Crops engineered to produce insecticidal crystal (Cry) proteins from the soil bacterium Bacillus thuringiensis (Bt) have revolutionised pest control in agriculture. However field-level resistance to Bt has developed in some targets. Utilising novel vegetative insecticidal proteins (Vips), also derived from Bt but genetically distinct from Cry toxins, is a possible solution that biotechnical companies intend to employ. Using data collected over two seasons we determined that, before deployment of Vip-expressing plants in Australia, resistance alleles exist in key targets as polymorphisms at frequencies of 0.027 (n = 273 lines, 95% CI = 0.019-0.038) in H. armigera and 0.008 (n = 248 lines, 0.004-0.015) in H. punctigera. These frequencies are above mutation rates normally encountered. Homozygous resistant neonates survived doses of Vip3A higher than those estimated in field-grown plants. Fortunately the resistance is largely, if not completely, recessive and does not confer resistance to the Bt toxins Cry1Ac or Cry2Ab already deployed in cotton crops. These later characteristics are favourable for resistance management; however the robustness of Vip3A inclusive varieties will depend on resistance frequencies to the Cry toxins when it is released (anticipated 2016) and the efficacy of Vip3A throughout the season. It is appropriate to pre-emptively screen key targets of Bt crops elsewhere, especially those such as H. zea in the USA, which is not only closely related to H. armigera but also will be exposed to Vip in several varieties of cotton and corn.

  12. Resistance to aspirin is increased by ST-elevation myocardial infarction and correlates with adenosine diphosphate levels

    PubMed Central

    Borna, Catharina; Lazarowski, Eduardo; van Heusden, Catharina; Öhlin, Hans; Erlinge, David

    2005-01-01

    Background To be fully activated platelets are dependent on two positive feedback loops; the formation of thromboxane A2 by cyclooxygenase in the platelets and the release of ADP. We wanted to evaluate the effect of aspirin on platelet function in patients with acute coronary syndromes and we hypothesized that increased levels of ADP in patients with acute coronary syndromes could contribute to aspirin resistance. Methods Platelet activity in 135 patients admitted for chest pain was assessed with PFA-100. An epinephrine-collagen cartridge (EPI-COLL) was used for the detection of aspirin resistance together with an ADP-collagen cartridge (ADP-COLL). ADP was measured with hplc from antecubital vein samples. Three subgroups were compared: chest pain with no sign of cardiac disease (NCD), NonST-elevation myocardial infarction (NSTEMI) and STEMI. Results Platelet activation was increased for the STEMI group compared NCD. Aspirin resistance defined as <193 sec in EPI-COLL was 9.7 % in NCD, and increased to 26.0 % (n.s.) in NSTEMI and 83.3 % (p < 0.001) in STEMI. Chronic aspirin treatment significantly reduced platelet aggregation in NCD and NSTEMI, but it had no effect in STEMI. Plasma levels of ADP were markedly increased in STEMI (905 ± 721 nmol/l, p < 0.01), but not in NSTEMI (317 ± 245), compared to NCD (334 ± 271, mean ± SD). ADP levels correlated with increased platelet activity measured with ADP-COLL (r = -0.30, p < 0.05). Aspirin resistant patients (EPI-COLL < 193 sec) had higher ADP levels compared to aspirin responders (734 ± 807 vs. 282 ± 187 nmol/l, mean ± SD, p < 0.05). Conclusion Platelets are activated and aspirin resistance is more frequent in STEMI, probably due to a general activation of platelets. ADP levels are increased in STEMI and correlates with platelet activation. Increased levels of ADP could be one reason for increased platelet activity and aspirin resistance. PMID:16045804

  13. Cisplatin-resistant cells express increased levels of a factor that recognizes damaged DNA

    SciTech Connect

    Chu, G.; Chang, E. )

    1990-05-01

    Cancer treatment with the drug cisplatin is often thwarted by the emergence of drug-resistant cells. To study this phenomenon, the authors identified two independent cellular factors that recognize cisplatin-damaged DNA. One of the two factors, designated XPE binding factor, is deficient in complementation group E of xeroderma pigmentosum, an inherited disease characterized by defective repair of DNA damaged by ultraviolet radiation, cisplatin, and other agents. Human tumor cell lines selected for resistance to cisplatin showed more efficient DNA repair and increased expression of XPE binding factor. These results suggest that XPE binding factor may be responsible, at least in part, for the development of cisplatin resistance in human tumors and that the mechanism may be increased DNA repair.

  14. Insulin resistance is associated with elevated serum pigment epithelium-derived factor (PEDF) levels in morbidly obese patients.

    PubMed

    Gattu, Arijeet K; Birkenfeld, Andreas L; Jornayvaz, Francois; Dziura, James; Li, Fangyong; Crawford, Susan E; Chu, Xin; Still, Christopher D; Gerhard, Glenn S; Chung, Chuhan; Samuel, Varman

    2012-12-01

    Obesity is a significant risk factor for developing diabetes. Pigment epithelium-derived factor (PEDF) has been identified by experimental and clinical studies as both a causative and counter-regulatory factor in the metabolic syndrome. We set out to determine whether serum PEDF levels correlated with the degree of insulin resistance in morbidly obese patients. Sera from 53 patients who were evaluated prior to gastric bypass surgery were analyzed for PEDF levels using a commercial ELISA. None of the patients were on diabetes medications prior to enrollment. Baseline data included BMI, serum glucose and insulin, and homeostasis model assessment (HOMA) scores. Patients were stratified based on HOMA score and glucose levels into three groups: insulin sensitive (IS): HOMA <2 and glucose <126; insulin resistant (IR): HOMA >2 and glucose ≤126; and diabetes mellitus (DM): HOMA >2 and glucose >126. Pre- and post-gastric bypass sera from 12 patients were obtained for serial assessment of metabolic parameters and PEDF levels. PEDF secretion was assessed in primary human hepatocytes, HCC cells, and cultured adipocytes in the absence and presence of high glucose media. No significant differences in age, gender, and BMI were found among the three groups. PEDF levels were similar between IR patients and the other groups, but were significantly higher in DM compared to IS patients (p = 0.01). Serum PEDF in individual patients declined significantly after gastric bypass (p = 0.006). High glucose media led to significantly higher PEDF release by human hepatocytes in vitro (p = 0.016). These data demonstrate that serum PEDF concentrations better relate to insulin resistance than to adiposity and suggest that PEDF expression is closely linked to the development of insulin resistance.

  15. Salvianolic acid B reverses multidrug resistance in HCT‑8/VCR human colorectal cancer cells by increasing ROS levels.

    PubMed

    Guo, Piaoting; Wang, Songpo; Liang, Wei; Wang, Wenjing; Wang, Huijun; Zhao, Miaomiao; Liu, Xiaowei

    2017-02-01

    Salvianolic acid B (SalB) a water‑soluble phenolic compound, extracted from Salvia miltiorrhiza, has previously been demonstrated to reverse tumor multidrug resistance (MDR), including in colorectal cancer. Reactive oxygen species (ROS) are oxygen radicals generated during aerobic metabolism (superoxide and hydroxyl radicals) and superoxide easily generating free radicals (H2O2). The concept that increased ROS levels can lead to augmented tumor cell‑sensitivity to chemotherapy drugs has become notable. The aim of the present study was to elucidate the role of ROS in mediating the effect of SalB on drug resistance and the correlation with drug resistance‑associated protein, P‑glycoprotein (P‑gp), and apoptosis‑associated proteins, B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X (Bax). In the current study, through utilizing the multidrug resistant colorectal cancer cell line, HCT‑8/VCR, it was demonstrate that SalB reversed MDR in HCT‑8/VCR. In addition, SalB significantly increased ROS levels, which may have accelerated the apoptosis of HCT‑8/VCR cells by downregulating Bcl‑2 and increasing Bax protein expression. Furthermore the increased intracellular ROS levels may have inhibited P‑gp expression at the gene and protein levels. In conclusion, the data of the current study demonstrate that SalB reversed MDR in HCT‑8/VCR cells, and the effect is associated with increased ROS levels, which may downregulate P‑gp expression and promote tumor cell apoptosis, which in turn increases the sensitivity of drug‑resistant cells to chemotherapy drugs.

  16. Increased serum resistin levels in patients with type 2 diabetes are not linked with markers of insulin resistance and adiposity.

    PubMed

    Hasegawa, G; Ohta, M; Ichida, Y; Obayashi, H; Shigeta, M; Yamasaki, M; Fukui, M; Yoshikawa, T; Nakamura, N

    2005-06-01

    The role of resistin in human biology remains uncertain. We measured serum resistin levels in Japanese patients with (n=111) and without (n=98) type 2 diabetes mellitus and investigated the significance of this hormone in the pathophysiology of diabetes. The levels of serum adiponectin and leptin were also measured. Resistin levels were increased significantly in patients with type 2 diabetes compared with non-diabetic subjects (24.7+/-2.6 vs. 15.0+/-1.2 ng/ml, p=0.0013). However, there was no correlation in either patient group between serum resistin levels and markers of insulin resistance, obesity or hyperlipidaemia. These results were in direct contrast to the data of leptin or adiponectin, both of which were closely related to these clinical markers of diabetes. Multivariate regression analysis on the combined data of the two groups demonstrated that the presence of diabetes and HDL cholesterol levels were significant predictors of serum resistin levels (diabetes: beta=0.159, p=0.035; HDL: beta=-0.172, p=0.039). No correlation was observed between C-reactive protein and resistin adjusted for BMI. Taken together, these findings demonstrate that serum resistin levels are increased in patients with type 2 diabetes, but this increase is not linked to markers of insulin resistance or adiposity. Further studies are necessary to elucidate the significance of serum resistin concentration in human pathophysiology.

  17. Mutations in pepQ Confer Low-Level Resistance to Bedaquiline and Clofazimine in Mycobacterium tuberculosis

    PubMed Central

    Almeida, Deepak; Ioerger, Thomas; Tyagi, Sandeep; Li, Si-Yang; Mdluli, Khisimuzi; Andries, Koen; Grosset, Jacques; Sacchettini, Jim

    2016-01-01

    The novel ATP synthase inhibitor bedaquiline recently received accelerated approval for treatment of multidrug-resistant tuberculosis and is currently being studied as a component of novel treatment-shortening regimens for drug-susceptible and multidrug-resistant tuberculosis. In a limited number of bedaquiline-treated patients reported to date, ≥4-fold upward shifts in bedaquiline MIC during treatment have been attributed to non-target-based mutations in Rv0678 that putatively increase bedaquiline efflux through the MmpS5-MmpL5 pump. These mutations also confer low-level clofazimine resistance, presumably by a similar mechanism. Here, we describe a new non-target-based determinant of low-level bedaquiline and clofazimine cross-resistance in Mycobacterium tuberculosis: loss-of-function mutations in pepQ (Rv2535c), which corresponds to a putative Xaa-Pro aminopeptidase. pepQ mutants were selected in mice by treatment with clinically relevant doses of bedaquiline, with or without clofazimine, and were shown to have bedaquiline and clofazimine MICs 4 times higher than those for the parental H37Rv strain. Coincubation with efflux inhibitors verapamil and reserpine lowered bedaquiline MICs against both mutant and parent strains to a level below the MIC against H37Rv in the absence of efflux pump inhibitors. However, quantitative PCR (qPCR) revealed no significant differences in expression of Rv0678, mmpS5, or mmpL5 between mutant and parent strains. Complementation of a pepQ mutant with the wild-type gene restored susceptibility, indicating that loss of PepQ function is sufficient for reduced susceptibility both in vitro and in mice. Although the mechanism by which mutations in pepQ confer bedaquiline and clofazimine cross-resistance remains unclear, these results may have clinical implications and warrant further evaluation of clinical isolates with reduced susceptibility to either drug for mutations in this gene. PMID:27185800

  18. Mutations in pepQ Confer Low-Level Resistance to Bedaquiline and Clofazimine in Mycobacterium tuberculosis.

    PubMed

    Almeida, Deepak; Ioerger, Thomas; Tyagi, Sandeep; Li, Si-Yang; Mdluli, Khisimuzi; Andries, Koen; Grosset, Jacques; Sacchettini, Jim; Nuermberger, Eric

    2016-08-01

    The novel ATP synthase inhibitor bedaquiline recently received accelerated approval for treatment of multidrug-resistant tuberculosis and is currently being studied as a component of novel treatment-shortening regimens for drug-susceptible and multidrug-resistant tuberculosis. In a limited number of bedaquiline-treated patients reported to date, ≥4-fold upward shifts in bedaquiline MIC during treatment have been attributed to non-target-based mutations in Rv0678 that putatively increase bedaquiline efflux through the MmpS5-MmpL5 pump. These mutations also confer low-level clofazimine resistance, presumably by a similar mechanism. Here, we describe a new non-target-based determinant of low-level bedaquiline and clofazimine cross-resistance in Mycobacterium tuberculosis: loss-of-function mutations in pepQ (Rv2535c), which corresponds to a putative Xaa-Pro aminopeptidase. pepQ mutants were selected in mice by treatment with clinically relevant doses of bedaquiline, with or without clofazimine, and were shown to have bedaquiline and clofazimine MICs 4 times higher than those for the parental H37Rv strain. Coincubation with efflux inhibitors verapamil and reserpine lowered bedaquiline MICs against both mutant and parent strains to a level below the MIC against H37Rv in the absence of efflux pump inhibitors. However, quantitative PCR (qPCR) revealed no significant differences in expression of Rv0678, mmpS5, or mmpL5 between mutant and parent strains. Complementation of a pepQ mutant with the wild-type gene restored susceptibility, indicating that loss of PepQ function is sufficient for reduced susceptibility both in vitro and in mice. Although the mechanism by which mutations in pepQ confer bedaquiline and clofazimine cross-resistance remains unclear, these results may have clinical implications and warrant further evaluation of clinical isolates with reduced susceptibility to either drug for mutations in this gene.

  19. Comparative Study of Serum Leptin and Insulin Resistance Levels Between Korean Postmenopausal Vegetarian and Non-vegetarian Women.

    PubMed

    Kim, Mi-Hyun; Bae, Yun-Jung

    2015-07-01

    The present study was conducted to compare serum leptin and insulin resistance levels between Korean postmenopausal long-term semi-vegetarians and non-vegetarians. Subjects of this study belonged to either a group of postmenopausal vegetarian women (n = 54), who maintained a semi-vegetarian diet for over 20 years or a group of non-vegetarian controls. Anthropometric characteristics, serum leptin, serum glucose, serum insulin, insulin resistance (HOMA-IR; Homeostasis Model Assessment of Insulin Resistance), and nutrient intake were compared between the two groups. The vegetarians showed significantly lower body weight (p < 0.01), body mass index (p < 0.001), percentage (%) of body fat (p < 0.001), and serum levels of leptin (p < 0.05), glucose (p < 0.001), and insulin (p < 0.01), than the non-vegetarians. The HOMA-IR of the vegetarians was significantly lower than that of the non-vegetarians (p < 0.01) after adjustment for the % of body fat. A long-term vegetarian diet might be related to lower insulin resistance independent of the % of body fat in postmenopausal women.

  20. Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility

    PubMed Central

    Pinsky, Benjamin A.; Smith, Darvin S.; Klein, Daniel; Shafer, Robert W.

    2016-01-01

    Abstract The integrase strand transfer inhibitor (INSTI)-resistance mutations Q148H/K/R are arguably the most important INSTI-resistance mutations as they represented the first step to high-level dolutegravir cross-resistance. We describe an individual with transmitted four-class drug resistance whose virus sequence had the previously uncharacterized mutation Q148N. Infectious molecular HIV-1 clones containing Q148N alone and in combination with G140S demonstrated ∼2.4–4.5 reduced elvitegravir susceptibility depending on the virus's genetic context but retained susceptibility to raltegravir and dolutegravir. This level of reduced elvitegravir susceptibility is lower than that observed with Q148H/K/R and in fact the infected individual responded to an initial treatment regimen containing tenofovir/emtricitabine/elvitegravir/cobicistat. Q148N was associated with a higher replication capacity than Q148H, suggesting that this mutation may be more fit in the absence of selective INSTI therapy. PMID:27009474

  1. Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility.

    PubMed

    Varghese, Vici; Pinsky, Benjamin A; Smith, Darvin S; Klein, Daniel; Shafer, Robert W

    2016-07-01

    The integrase strand transfer inhibitor (INSTI)-resistance mutations Q148H/K/R are arguably the most important INSTI-resistance mutations as they represented the first step to high-level dolutegravir cross-resistance. We describe an individual with transmitted four-class drug resistance whose virus sequence had the previously uncharacterized mutation Q148N. Infectious molecular HIV-1 clones containing Q148N alone and in combination with G140S demonstrated ∼2.4-4.5 reduced elvitegravir susceptibility depending on the virus's genetic context but retained susceptibility to raltegravir and dolutegravir. This level of reduced elvitegravir susceptibility is lower than that observed with Q148H/K/R and in fact the infected individual responded to an initial treatment regimen containing tenofovir/emtricitabine/elvitegravir/cobicistat. Q148N was associated with a higher replication capacity than Q148H, suggesting that this mutation may be more fit in the absence of selective INSTI therapy.

  2. High-level vancomycin resistant Enterococcus faecium related to humans and pigs found in dust from pig breeding facilities.

    PubMed

    Braga, Teresa M; Pomba, Constança; Lopes, M Fátima Silva

    2013-01-25

    Environmental dust from animal breeding facilities was never screened for the presence of enterococci, nor of vancomycin-resistant enterococci (VRE), despite the possibility of being a vehicle of transmission of strains and antibiotic resistance genes between food-producing animals and man. Bio-security measures in pig facilities include disinfection with biocides to avoid the dissemination of opportunistic pathogenic bacteria, namely enterococci and in particular VRE. We thus undertook collection of enterococci and VRE in a representative number of breeding pig facilities in Portugal (n=171) and analyzed their susceptibility to benzalkonium chloride (BC) and chlorhexidine (CHX). A prevalence of 15% of VRE was found, with 6% high-level resistance found, and MIC values for CHX and BC were similar to those commonly found among enterococcal isolates from related environments, 8 μg/ml and 4 μg/ml, respectively. Among the isolated high-level vancomycin resistant Enterococcus faecium carrying the vanA genotype, we found multilocus sequence types closely related to pig and human isolates from European countries and Brazil. These results strongly advise constant surveillance of this environment and its inclusion in future epidemiologic studies on VRE.

  3. Prevalence of carbapenemases among high-level aminoglycoside-resistant Acinetobacter baumannii isolates in a university hospital in China

    PubMed Central

    Wang, Yanhong; Shen, Min; Yang, Jingni; Dai, Min; Chang, Yaowen; Zhang, Chi; Luan, Guangxin; Ling, Baodong; Jia, Xu

    2016-01-01

    The prevalence of aminoglycoside resistant enzymes has previously been reported and extended-spectrum β-lactamase among Acinetobacter baumannii. To track the risk of multidrug-resistant A. baumannii, the present study aimed to determine the prevalence of carbapenemases in high-level aminoglycoside resistant A. baumannii over two years. A total of 118 strains of A. baumannii were consecutively collected in the First Affiliated Hospital of Chengdu Medical College, Chengdu, China. These isolates were investigated on the genetic basis of their resistance to aminoglycosides. The results showed that 75 (63.56%) isolates were high-level resistant to aminoglycosides, including gentamicin and amikacin (minimum inhibitory concentration, ≥256 µg/ml). Aminoglycoside-resistant genes ant(2″)-Ia, aac(6′)-Ib, aph(3′)-Ia, aac(3)-Ia, aac(3)-IIa, armA, rmtA, rmtB, rmtC, rmtD, rmtE, rmtF, rmtG, rmtH and npmA, and carbapenem-resistant genes blaOXA-23, blaOXA-24, blaOXA-51, blaOXA-58, blaSIM, blaIMP, blaNDM-1 and blaKPC, were analyzed using polymerase chain reaction. The positive rate of ant(2″)-Ia, aac(6′)-Ib, aph(3′)-Ia, aac(3)-Ia and aac(3)-IIa was 66.95, 69.49, 42.37, 39.83 and 14.41%, respectively. armA was present in 72.0% (54/75) of A. baumannii isolates with high-level resistance to aminoglycosides. The remaining nine 16S ribosomal RNA methlyase genes (rmtA, rmtB, rmtC, rmtD, rmtE, rmtF, rmtG, rmtH and npmA) and aminoglycoside-modifying enzyme gene aac(6′)-Ib-cr were not detected. Among the 54 armA-positive isolates, the prevalence of the carbapenem resistant blaOXA-23 and blaOXA-51 genes was 79.63 and 100%, respectively. armA, ant(2″)-Ia and aac(6′)-Ib were positive in 43 isolates. The results of multilocus sequence typing revealed 31 sequence types (STs) in all clinical strains. Among these STs, the high-level aminoglycoside-resistant A. baumannii ST92, which mostly harbored blaOXA-23, was the predominant clone (29/75). In conclusion, A. baumannii

  4. Elevated resistin levels induce central leptin resistance and increased atherosclerotic progression in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Resistin was originally identified as an adipocyte-derived factor upregulated during obesity and as a contributor to obesity-associated insulin resistance. Clinically, resistin has also been implicated in cardiovascular disease in a number of different patient populations. Our aim was to simultaneou...

  5. A Bioassay for Determining Resistance Levels in Tarnished Plant Bug Populations to Neonicotinoid Insecticides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A laboratory bioassay was developed and used to test field populations of the tarnished plant bug, Lygus lineolaris (Palisot de Beauvois), for resistance development to the neonicitinoid insecticides imidacloprid (Trimax®) and thiamethoxam (Centric®). The bioassay determined LC50 values by feeding...

  6. Draft Genome Sequences of Streptococcus pneumoniae with High-Level Resistance to Respiratory Fluoroquinolones.

    PubMed

    Keness, Yoram; Bisharat, Naiel

    2016-03-31

    Streptococcus pneumoniaeis the leading cause of community-acquired pneumonia. Levofloxacin is a fluoroquinolone used for treatment of severe community-acquired pneumonia. Here, we describe the draft genome sequences ofS. pneumoniaewith emerging resistance to levofloxacin, resulting in failure of treatment of pneumococcal pneumonia.

  7. Insulin resistance and adipokine levels correlate with early atherosclerosis – a study in prediabetic patients

    PubMed Central

    Mihai, Bogdan Mircea; Petriş, Antoniu Octavian; Ungureanu, Didona Anca

    2015-01-01

    Cardiovascular risk of prediabetes is still subject to controversies. We analyzed the associations between insulin resistance, adipokines and incipient atherosclerosis estimated by intima-media thickness (IMT) in a cross-sectional study on 122 prediabetic subjects without clinical signs of atherosclerotic disease. Homeostasis model assessment of insulin resistance (HOMA-IR, calculated as fasting insulin × fasting plasma glucose / 22.5), adiponectin, leptin, leptin-to-adiponectin ratio, carotid and femoral IMT were evaluated. We also assessed other parameters related to insulin resistance and adipokines (HbA1c, anthropometric and lipid parameters), as they may also influence atherosclerosis. Carotid IMT was correlated to adiponectin and leptin-to-adiponectin ratio (all p < 0.05), but not with HOMA-IR or leptin, while femoral IMT showed no relationship with these factors. After adjusting for leptin, leptin-to-adiponectin ratio, triglycerides, HDL-cholesterol, cholesterol-to-HDL ratio, triglycerides-to-HDL ratio and HbA1c, IMT values became correlated with HOMA-IR. Adjustment for HOMA-IR induced the appearance of new correlations between adipokines and both IMT values. In conclusion, insulin resistance and adipokines seem related to IMT in prediabetic subjects without clinical signs of arterial obstruction. PMID:28352672

  8. Monooxygenase Levels and Knockdown Resistance (kdr) Allele Frequencies in Anopheles gambiae and Anopheles arabiensis in Kenya

    PubMed Central

    Chen, Hong; Githeko, Andrew K; Githure, John I; Mutunga, James; Zhou, Guofa; Yan, Guiyun

    2013-01-01

    Pyrethroid-treated bed nets and indoor spray are important components of malaria control strategies in Kenya. Information on resistance to pyrethroid insecticides in Anopheles gambiae and An. arabiensis populations is essential to the selection of appropriate insecticides and the management of insecticide resistance. Monooxygenase activity and knockdown resistance (kdr) allele frequency are biochemical and molecular indicators of mosquito resistance to pyrethroids. This study determined baseline information on monooxygenase activity and kdr allele frequency in anopheline mosquitoes in the western region, the Great Rift Valley-central province region, and the coastal region of Kenya. A total of 1990 field-collected individuals, representing 12 An. gambiae and 22 An. arabiensis populations was analyzed. We found significant among-population variation in monooxygenase activity in An. gambiae and An. arabiensis and substantial variability among individuals within populations. Nine out of 12 An. gambiae populations exhibited significantly higher average monooxygenase activity than the susceptible Kisumu reference strain. The kdr alleles (L1014S) were detected in three An. gambiae populations, and one An. arabiensis population in western Kenya, but not in the Rift Valley-central region and the coastal Kenya region. All genotypes with the kdr alleles were heterozygous, and the conservative estimation of kdr allele frequency was below 1% in these four populations. Information on monooxygenase activity and kdr allele frequency reported in this study provided baseline data for monitoring insecticide resistance changes in Kenya during the era when large-scale insecticide-treated bednet and indoor residual spray campaigns were being implemented. PMID:18402140

  9. Low level ß-lactamase production in methicillin-resistant staphylococcus aureus strains with ß-lactam antibiotics-induced vancomycin resistance

    PubMed Central

    2012-01-01

    Background A class of methicillin-resistant Staphylococcus aureus (MRSA) shows resistance to vancomycin only in the presence of ß-lactam antibiotics (BIVR). This type of vancomycin resistance is mainly attributable to the rapid depletion of free vancomycin in the presence of ß-lactam antibiotics. This means that ß-lactam antibiotics remain active or intact in BIVR culture, although most MRSA cells are assumed to produce ß-lactamase. We hypothesised that the BIVR cells either did not harbour the ß-lactamase gene, blaZ, or the gene was quiescent. We tested this hypothesis by determining ß-lactamase activity and conducting PCR amplification of blaZ. Results Five randomly selected laboratory stock BIVR strains showed an undetectable level of ß-lactamase activity and were blaZ-negative. Five non-BIVR stock strains showed an average ß-lactamase activity of 2.59 ± 0.35 U. To test freshly isolated MRSA, 353 clinical isolates were collected from 11 regionally distant hospitals. Among 25 BIVR strains, only 16% and 8% were blaZ positive and ß-lactamase-positive, respectively. In contrast, 95% and 61% of 328 non-BIVR strains had the blaZ gene and produced active ß-lactamase, respectively. To know the mechanism of low ß-lactamase activity in the BIVR cells, they were transformed with the plasmid carrying the blaZ gene. The transformants still showed a low level of ß-lactamase activity that was several orders of magnitude lower than that of blaZ-positive non-BIVR cells. Presence of the ß-lactamase gene in the transformants was tested by PCR amplification of blaZ using 11 pairs of primers covering the entire blaZ sequence. Yield of the PCR products was consistently low compared with that using blaZ-positive non-BIVR cells. Nucleotide sequencing of blaZ in one of the BIVR transformants revealed 10 amino acid substitutions. Thus, it is likely that the ß-lactamase gene was modified in the BIVR cells to downregulate active ß-lactamase production. Conclusions We

  10. Draft Genome Sequence of a High-Level Colistin-Resistant Clinical Strain of the Enterobacter cloacae Complex

    PubMed Central

    Lin, Ji; Zhao, Feifei; Feng, Yu

    2017-01-01

    ABSTRACT Strain WCHECl-C4 of the Enterobacter cloacae complex, recovered from the blood of a patient with peritonitis, was high-level resistant to colistin. Here, we report its 5.1-Mb draft genome sequence, comprising 92 contigs with an average 55.74% G+C content. The genome contained 4,783 coding sequences and 68 tRNA genes. PMID:28385849

  11. Induction of Fibronectin-Binding Proteins and Increased Adhesion of Quinolone-Resistant Staphylococcus aureus by Subinhibitory Levels of Ciprofloxacin

    PubMed Central

    Bisognano, Carmelo; Vaudaux, Pierre; Rohner, Peter; Lew, Daniel P.; Hooper, David C.

    2000-01-01

    We recently reported that strain EN1252a, a fluoroquinolone-resistant derivative of Staphylococcus aureus NCTC8325 with mutations in grlA and gyrA, expressed increased levels of fibronectin-binding proteins (FnBPs) and showed a significantly higher attachment to fibronectin-coated polymer surfaces after growth in the presence of subinhibitory concentrations of ciprofloxacin. The present study evaluated the occurrence and frequency of fluoroquinolone-induced FnBP-mediated adhesion in clinical isolates of fluoroquinolone-resistant methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA). Eight of ten MRSA isolates and four of six MSSA isolates with grlA and gyrA mutations exhibited significant increases in attachment to fibronectin-coated surfaces after growth in the presence of one-quarter the MIC of ciprofloxacin. Fluoroquinolone-induced FnBP-mediated adhesion of one clinical MRSA strain and the double mutant strain EN1252a also occurred on coverslips removed from the subcutaneous space of guinea pigs. For strain EN1252a, the regulation of fnb transcription by sub-MICs of ciprofloxacin was studied on reporter plasmids carrying fnb-luxAB fusions. One-quarter of the MIC of ciprofloxacin significantly increased fnbB, but not fnbA, promoter activity of the fluoroquinolone-resistant mutant but not its fluoroquinolone-susceptible parent ISP794. This response was abolished by pretreatment with rifampin, indicating an effect at the level of transcription. Activation of the fnbB promoter was not due to an indirect effect of ciprofloxacin on growth rate and still occurred in an agr mutant of strain EN1252a. These data suggest that sub-MIC levels of ciprofloxacin activate the fnbB promoter of some laboratory and clinical isolates, thus contributing to increased production of FnBP(s) and leading to higher levels of bacterial attachment to fibronectin-coated or subcutaneously implanted coverslips. PMID:10817688

  12. Association between serum gonadotropin level and insulin resistance-related parameters in Korean women with polycystic ovary syndrome

    PubMed Central

    Park, Chan-Hong

    2016-01-01

    Objective To evaluate the relationship between serum gonadotropin level and parameters related to insulin resistance in Korean women with polycystic ovary syndrome (PCOS). Methods This retrospective study included 138 women aged 18 to 35 years who were newly diagnosed with PCOS according to the Rotterdam consensus. Participants were divided into three groups based on the serum luteinizing hormone to follicle-stimulating hormone (LH/FSH) ratio in the early follicular phase: group 1 (LH/FSH <1), group 2 (1.0≤ LH/FSH >2.0), and group 3 (LH/FSH ≥2.0). The correlations between the LH/FSH ratio and various metabolic parameters were evaluated using Pearson correlation coefficients. Results Patients with higher LH/FSH ratios showed higher total antral follicle counts and higher total ovarian volume. In the comparison of anthropometric and biochemical parameters among the three groups, the waist to hip ratio was the only parameter that differed significantly among the groups (P=0.003). Correlation analysis revealed no significant correlations between serum LH/FSH ratios and biochemical parameters related to insulin resistance. However, after adjustments for age and body mass index, a significant correlation between total cholesterol level and serum LH/FSH ratio was observed (r=0.221, P=0.018). Conclusion Most parameters related to insulin resistance, with the exception of total cholesterol level, are unrelated to the inappropriate pattern of serum gonadotropin secretion in Korean women with PCOS. PMID:27896252

  13. Influence of resistance and aerobic exercise on hunger, circulating levels of acylated ghrelin, and peptide YY in healthy males.

    PubMed

    Broom, David R; Batterham, Rachel L; King, James A; Stensel, David J

    2009-01-01

    Resistance (muscle strengthening) exercise is a key component of exercise recommendations for weight control, yet very little is known about the effects of resistance exercise on appetite. We investigated the effects of resistance and aerobic exercise on hunger and circulating levels of the gut hormones acylated ghrelin and peptide YY (PYY). Eleven healthy male students: age 21.1 +/- 0.3 yr, body mass index 23.1 +/- 0.4 kg/m(2), maximum oxygen uptake 62.1 +/- 1.8 ml.kg(-1).min(-1) (means +/- SE) undertook three, 8-h trials, 1) resistance exercise: a 90-min free weight lifting session followed by a 6.5-h rest period, 2) aerobic exercise: a 60-min run followed by a 7-h rest period, 3) control: an 8-h rest, in a randomized crossover design. Meals were provided 2 and 5 h into each trial. Hunger ratings and plasma concentrations of acylated ghrelin and PYY were measured throughout. Two-way ANOVA revealed significant (P < 0.05) interaction effects for hunger, acylated ghrelin, and PYY, indicating suppressed hunger and acylated ghrelin during aerobic and resistance exercise and increased PYY during aerobic exercise. A significant trial effect was observed for PYY, indicating higher concentrations on the aerobic exercise trial than the other trials (8 h area under the curve: control 1,411 +/- 110, resistance 1,381 +/- 97, aerobic 1,750 +/- 170 pg/ml 8 h). These findings suggest ghrelin and PYY may regulate appetite during and after exercise, but further research is required to establish whether exercise-induced changes in ghrelin and PYY influence subsequent food intake.

  14. TM-25659-Induced Activation of FGF21 Level Decreases Insulin Resistance and Inflammation in Skeletal Muscle via GCN2 Pathways.

    PubMed

    Jung, Jong Gab; Yi, Sang-A; Choi, Sung-E; Kang, Yup; Kim, Tae Ho; Jeon, Ja Young; Bae, Myung Ae; Ahn, Jin Hee; Jeong, Hana; Hwang, Eun Sook; Lee, Kwan-Woo

    2015-12-01

    The TAZ activator 2-butyl-5-methyl-6-(pyridine-3-yl)-3-[2'-(1H-tetrazole-5-yl)-biphenyl-4-ylmethyl]-3H-imidazo[4,5-b]pyridine] (TM-25659) inhibits adipocyte differentiation by interacting with peroxisome proliferator-activated receptor gamma. TM-25659 was previously shown to decrease weight gain in a high fat (HF) diet-induced obesity (DIO) mouse model. However, the fundamental mechanisms underlying the effects of TM-25659 remain unknown. Therefore, we investigated the effects of TM-25659 on skeletal muscle functions in C2 myotubes and C57BL/6J mice. We studied the molecular mechanisms underlying the contribution of TM-25659 to palmitate (PA)-induced insulin resistance in C2 myotubes. TM-25659 improved PA-induced insulin resistance and inflammation in C2 myotubes. In addition, TM-25659 increased FGF21 mRNA expression, protein levels, and FGF21 secretion in C2 myotubes via activation of GCN2 pathways (GCN2-phosphoeIF2α-ATF4 and FGF21). This beneficial effect of TM-25659 was diminished by FGF21 siRNA. C57BL/6J mice were fed a HF diet for 30 weeks. The HF-diet group was randomly divided into two groups for the next 14 days: the HF-diet and HF-diet + TM-25659 groups. The HF diet + TM-25659-treated mice showed improvements in their fasting blood glucose levels, insulin sensitivity, insulin-stimulated Akt phosphorylation, and inflammation, but neither body weight nor food intake was affected. The HF diet + TM-25659-treated mice also exhibited increased expression of both FGF21 mRNA and protein. These data indicate that TM-25659 may be beneficial for treating insulin resistance by inducing FGF21 in models of PA-induced insulin resistance and HF diet-induced insulin resistance.

  15. Impaired fitness of human immunodeficiency virus type 1 variants with high-level resistance to protease inhibitors.

    PubMed Central

    Croteau, G; Doyon, L; Thibeault, D; McKercher, G; Pilote, L; Lamarre, D

    1997-01-01

    One hope to maintain the benefits of antiviral therapy against the human immunodeficiency virus type 1 (HIV-1), despite the development of resistance, is the possibility that resistant variants will show decreased viral fitness. To study this possibility, HIV-1 variants showing high-level resistance (up to 1,500-fold) to the substrate analog protease inhibitors BILA 1906 BS and BILA 2185 BS have been characterized. Active-site mutations V32I and I84V/A were consistently observed in the protease of highly resistant viruses, along with up to six other mutations. In vitro studies with recombinant mutant proteases demonstrated that these mutations resulted in up to 10(4)-fold increases in the Ki values toward BILA 1906 BS and BILA 2185 BS and a concomitant 2,200-fold decrease in catalytic efficiency of the enzymes toward a synthetic substrate. When introduced into viral molecular clones, the protease mutations impaired polyprotein processing, consistent with a decrease in enzyme activity in virions. Despite these observations, however, most mutations had little effect on viral replication except when the active-site mutations V32I and I84V/A were coexpressed in the protease. The latter combinations not only conferred a significant growth reduction of viral clones on peripheral blood mononuclear cells but also caused the complete disappearance of mutated clones when cocultured with wild-type virus on T-cell lines. Furthermore, the double nucleotide mutation I84A rapidly reverted to I84V upon drug removal, confirming its impact on viral fitness. Therefore, high-level resistance to protease inhibitors can be associated with impaired viral fitness, suggesting that antiviral therapies with such inhibitors may maintain some clinical benefits. PMID:8995629

  16. [Relationship between serum levels of C-reactive protein and alpha1-antitrypsin and insulin resistance in obese women].

    PubMed

    Ramírez Alvarado, María Matilde; Sánchez Roitz, César

    2014-09-01

    Adipose tissue produces cytokines involved in insulin resistance (IR) such as IL-6, IL-8, TNF-alpha and proinflammatory molecules such as C reactive protein (CRP). alpha1-antitrypsin is an inflammation-sensitive plasma protein. The objective of this study is to determine the correlation between serum CRP high-sensitivity (CRPhs) and alpha1-antitrypsin levels with IR indices in obese Venezuelan women. The study population consisted of 15 normal weight women (BMI 21.8 +/- 1.9 kg/m2) and 15 obese women (BMI 35.3 +/- 5.3 kg/m2). Obese and lean women underwent a 2 h-75 g oral glucose tolerance test and the following indices were calculated: homeostatic model assessment of insulin resistance (HOMA-IR), homeostatic model assessment of beta cell function (HOMA-beta), Matsuda Index and Insulinogenic Index. The relationship between serum CRPhs and alpha1-antitrypsin levels and these indices were determined. Obese women had higher CRPhs levels (p = 0.001) compared with normal weight women. In obese women, serum CRPhs levels were positively correlated with HOMA-IR (r = 0.73, p = 0.0021), HOMA-beta (r = 0.53, p = 0.031) and negatively correlated with the Matsuda Index (r = -0.60, p = 0.017). No correlation between serum levels of alpha1-antitrypsin and IR indices in the obese group and the lean group was observed. There was a relation between serum CRPhs levels and insulin resistance, suggesting a role of subclinical inflammation in IR.

  17. Evaluation of the Kirby-Bauer disc diffusion test as a screening test for high-level aminoglycoside resistance in enterococci.

    PubMed

    Pfaller, M A; Niles, A C; Murray, P R

    1984-10-01

    The Kirby-Bauer disc diffusion test was evaluated as a test to detect high-level aminoglycoside (streptomycin, kanamycin, tobramycin, and gentamicin) resistance in isolates of enterococci. The authors found that high-level resistance could not be predicted accurately with the diffusion test.

  18. Antibiotic administration routes significantly influence the levels of antibiotic resistance in gut microbiota.

    PubMed

    Zhang, Lu; Huang, Ying; Zhou, Yang; Buckley, Timothy; Wang, Hua H

    2013-08-01

    This study examined the impact of oral exposure to antibiotic-resistant bacteria and antibiotic administration methods on antibiotic resistance (AR) gene pools and the profile of resistant bacteria in host gastrointestinal (GI) tracts using C57BL/6J mice with natural gut microbiota. Mice inoculated with a mixture of tet(M)-carrying Enterococcus spp. or blaCMY-2-carrying Escherichia coli were treated with different doses of tetracycline hydrochloride (Tet) or ampicillin sodium (Amp) and delivered via either feed or intravenous (i.v.) injection. Quantitative PCR assessment of mouse fecal samples revealed that (i) AR gene pools were below the detection limit in mice without prior inoculation of AR gene carriers regardless of subsequent exposure to corresponding antibiotics; (ii) oral exposure to high doses of Tet and Amp in mice inoculated with AR gene carriers led to rapid enrichment of corresponding AR gene pools in feces; (iii) significantly less or delayed development of AR in the GI tract of the AR carrier-inoculated mice was observed when the same doses of antibiotics were administered via i.v. injection rather than oral administration; and (iv) antibiotic dosage, and maybe the excretion route, affected AR in the GI tract. The shift of dominant AR bacterial populations in the gut microbiota was consistent with the dynamics of AR gene pools. The emergence of endogenous resistant bacteria in the gut microbiota corresponding to drug exposure was also observed. Together, these data suggest that oral administration of antibiotics has a prominent effect on AR amplification and development in gut microbiota, which may be minimized by alternative drug administration approaches, as illustrated by i.v. injection in this study and proper drug selection.

  19. Modulation of DNA methylation levels sensitizes doxorubicin-resistant breast adenocarcinoma cells to radiation-induced apoptosis

    SciTech Connect

    Luzhna, Lidia; Kovalchuk, Olga

    2010-02-05

    Chemoresistant tumors often fail to respond to other cytotoxic treatments such as radiation therapy. The mechanisms of chemo- and radiotherapy cross resistance are not fully understood and are believed to be epigenetic in nature. We hypothesize that MCF-7 cells and their doxorubicin-resistant variant MCF-7/DOX cells may exhibit different responses to ionizing radiation due to their dissimilar epigenetic status. Similar to previous studies, we found that MCF-7/DOX cells harbor much lower levels of global DNA methylation than MCF-7 cells. Furthermore, we found that MCF-7/DOX cells had lower background apoptosis levels and were less responsive to radiation than MCF-7 cells. Decreased radiation responsiveness correlated to significant global DNA hypomethylation in MCF-7/DOX cells. Here, for the first time, we show that the radiation resistance of MCF-7/DOX cells can be reversed by an epigenetic treatment - the application of methyl-donor SAM. SAM-mediated reversal of DNA methylation led to elevated radiation sensitivity in MCF-7/DOX cells. Contrarily, application of SAM on the radiation sensitive and higher methylated MCF-7 cells resulted in a decrease in their radiation responsiveness. This data suggests that a fine balance of DNA methylation is needed to insure proper radiation and drug responsiveness.

  20. Effects of low-level ciprofloxacin challenge in the in vitro development of ciprofloxacin resistance in Campylobacter jejuni.

    PubMed

    Hannula, Minna; Hänninen, Marja-Liisa

    2008-09-01

    The effects on MIC values and the selection of different base substitutions in the quinolone resistance determining region (QRDR) of gyrA were studied on initially ciprofloxacin-susceptible Campylobacter jejuni strains by challenging them to 0.125 mg/L of ciprofloxacin. This ciprofloxacin challenge selected variants with ciprofloxacin MIC levels up to 32 mg/L. Repeated experiments under identical conditions resulted in different responses in MIC levels and alterations in the QRDR of gyrA. A characteristic outcome to ciprofloxacin challenges was the appearance of double peaks in the sequencing chromatograms of QRDR. This finding suggested the coexistence of subpopulations possessing Thr86 --> Ile and/or Asp90 --> Asn mutations alongside the unmutated parent population. In some cases, bacterial variants expressing ciprofloxacin-resistant phenotypes possessed no mutations in their QRDR. These variants were prone to regain susceptibility to ciprofloxacin rapidly after the removal of the selection pressure, whereas the QRDR-mutated variants persisted over several subcultivations in a medium without ciprofloxacin. In conclusion, a low ciprofloxacin concentration of 0.125 mg/L selects a variety of QRDR mutations and also a QRDR-independent resistance mechanism, which may coexist with each other in a C. jejuni population. Persistent ciprofloxacin challenge selects Thr86 --> Ile and/or Asp90 --> Asn mutants.

  1. Effects of medium and inoculum variations on screening for high-level aminoglycoside resistance in Enterococcus faecalis.

    PubMed Central

    Sahm, D F; Torres, C

    1988-01-01

    Enterococcus faecalis isolates that are refractory to aminoglycoside-penicillin synergy can be detected by their ability to grow in the presence of high concentrations of aminoglycoside (2,000 micrograms/ml). In past studies investigators have used a variety of media and inoculum sizes to perform high-level aminoglycoside resistance screens, but little is known about how these variations affect test accuracy. We screened 63 E. faecalis strains on different media by using various inoculum sizes and correlated the results with synergy test results obtained by time-kill studies. Screens were done with dextrose-phosphate agar, brain heart infusion agar, Trypticase soy agar with 5% sheep blood, Mueller-Hinton agar with 5% sheep blood, dextrose-phosphate broth, and Mueller-Hinton broth. Agar screens were inoculated with 10(2), 10(4), and 10(6) CFU; and broth screens contained a final inoculum of 10(5) CFU/ml. The E. faecalis isolates were tested for high-level resistance to streptomycin, kanamycin, amikacin, gentamicin, and tobramycin. Of the 63 isolates tested, 21 did not show high-level resistance to any of the aminoglycosides tested, and 42 demonstrated high-level resistance to one or more drugs. The sensitivity of most screens was greater than or equal to 90%. Regardless of the inoculum size or medium used, false-resistance results were seldom encountered. Screen specificity, which was used as the indicator of false susceptibility, was markedly influenced by both the inoculum size and the drug being tested. Specificity was low whenever a 10(2)-CFU inoculum was used, when amikacin was tested with any inoculum, and when tobramycin was tested in broth media. Data for kanamycin could be used to predict amikacin-penicillin synergy, and the highly accurate gentamicin screen obviated the need for the testing of tobramycin. We recommend a 10(6) -CFU inoculum for agar screens and a 10(5) -CFU/ml inoculum for broth screens. The type of medium used did not substantially

  2. High levels of pre-treatment HIV drug resistance and treatment failure in Nigerian children

    PubMed Central

    Boerma, Ragna S; Boender, T Sonia; Sigaloff, Kim C.E.; Rinke de Wit, Tobias F; van Hensbroek, Michael Boele; Ndembi, Nicaise; Adeyemo, Titilope; Temiye, Edamisan O; Osibogun, Akin; Ondoa, Pascale; Calis, Job C; Akanmu, Alani Sulaimon

    2016-01-01

    Introduction Pre-treatment HIV drug resistance (PDR) is an increasing problem in sub-Saharan Africa. Children are an especially vulnerable population to develop PDR given that paediatric second-line treatment options are limited. Although monitoring of PDR is important, data on the paediatric prevalence in sub-Saharan Africa and its consequences for treatment outcomes are scarce. We designed a prospective paediatric cohort study to document the prevalence of PDR and its effect on subsequent treatment failure in Nigeria, the country with the second highest number of HIV-infected children in the world. Methods HIV-1-infected children ≤12 years, who had not been exposed to drugs for the prevention of mother-to-child transmission (PMTCT), were enrolled between 2012 and 2013, and followed up for 24 months in Lagos, Nigeria. Pre-antiretroviral treatment (ART) population-based pol genotypic testing and six-monthly viral load (VL) testing were performed. Logistic regression analysis was used to assess the effect of PDR (World Health Organization (WHO) list for transmitted drug resistance) on subsequent treatment failure (two consecutive VL measurements >1000 cps/ml or death). Results Of the total 82 PMTCT-naïve children, 13 (15.9%) had PDR. All 13 children harboured non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations, of whom seven also had nucleoside reverse transcriptase inhibitor resistance. After 24 months, 33% had experienced treatment failure. Treatment failure was associated with PDR and a higher log VL before treatment initiation (adjusted odds ratio (aOR) 7.53 (95%CI 1.61–35.15) and 2.85 (95%CI 1.04–7.78), respectively). Discussion PDR was present in one out of six Nigerian children. These high numbers corroborate with recent findings in other African countries. The presence of PDR was relevant as it was the strongest predictor of first-line treatment failure. Conclusions Our findings stress the importance of implementing fully active regimens

  3. Efficacy of a trunk orthosis with joints providing resistive force on low back load during level walking in elderly persons

    PubMed Central

    Katsuhira, Junji; Matsudaira, Ko; Oka, Hiroyuki; Iijima, Shinno; Ito, Akihiro; Yasui, Tadashi; Yozu, Arito

    2016-01-01

    Purpose The effects of lumbosacral and spinal orthoses on low back pain and gait are not exactly clear. We previously developed a trunk orthosis with joints providing resistive force on low back load to decrease such load, and confirmed its positive effects during level walking in healthy young adults. Therefore, we aimed to determine the efficacy of this trunk orthosis during level walking in healthy elderly subjects. Methods Fifteen community-dwelling elderly subjects performed level walking at a self-selected speed without an orthosis, with our orthosis, and with a lumbosacral orthosis. Kinematic and kinetic data were recorded using a three-dimensional motion analysis system, and erector spinae activity was recorded by electromyography. Results When comparing the three conditions, our orthosis showed the following effects: it decreased the peak extension moment, increased the peak flexion moment, decreased the lateral bending angle, increased the peak thoracic extension angle, and had significantly lower erector spinae activity and significantly larger peak pelvic forward tilt angles. Conclusion Our orthosis with joints providing resistive force decreased low back load and modified trunk and pelvis alignments during level walking in healthy elderly people. PMID:27877028

  4. MAMA-PCR assay for the detection of point mutations associated with high-level erythromycin resistance in Campylobacter jejuni and Campylobacter coli strains.

    PubMed

    Alonso, Rodrigo; Mateo, Estibaliz; Churruca, Estibaliz; Martinez, Irati; Girbau, Cecilia; Fernández-Astorga, Aurora

    2005-10-01

    Twenty Campylobacter jejuni and 16 Campylobacter coli strains isolated from humans and food/animals, including 17 isolates resistant to erythromycin, were analyzed. A combined mismatch amplification mutation assay-PCR technique was developed to detect the mutations A 2074 C and A 2075 G in the 23S rRNA gene associated with erythromycin resistance. All high-level erythromycin-resistant strains examined by DNA sequencing carried the transition mutation A 2075 G, whereas no isolate carried the A 2074 C mutation. No mutations were found among the susceptible and low-level erythromycin-resistant strains.

  5. An Alteration of Lymphocytes Subpopulations and Immunoglobulins Levels in Patients with Diabetic Foot Ulcers Infected Particularly by Resistant Pathogens

    PubMed Central

    Jirkovská, Alexandra; Dubský, Michal; Game, Frances; Vydláková, Jana; Sekerková, Alena; Franeková, Jana; Kučerová, Monika; Stříž, Ilja; Petkov, Vladimír; Němcová, Andrea; Skibová, Jelena

    2016-01-01

    The aim of our study was to analyse immune abnormalities in patients with chronic infected diabetic foot ulcers (DFUs) especially those infected by resistant microorganisms. Methods. 68 patients treated in our foot clinic for infected chronic DFUs with 34 matched diabetic controls were studied. Patients with infected DFUs were subdivided into two subgroups according to the antibiotic sensitivity of causal pathogen: subgroup S infected by sensitive (n = 50) and subgroup R by resistant pathogens (n = 18). Selected immunological markers were compared between the study groups and subgroups. Results. Patients with infected chronic DFUs had, in comparison with diabetic controls, significantly reduced percentages (p < 0.01) and total numbers of lymphocytes (p < 0.001) involving B lymphocytes (p < 0.01), CD4+ (p < 0.01), and CD8+ T cells (p < 0.01) and their naive and memory effector cells. Higher levels of IgG (p < 0.05) including IgG1 (p < 0.001) and IgG3 (p < 0.05) were found in patients with DFUs compared to diabetic controls. Serum levels of immunoglobulin subclasses IgG2 and IgG3 correlated negatively with metabolic control (p < 0.05). A trend towards an increased frequency of IgG2 deficiency was found in patients with DFUs compared to diabetic controls (22% versus 15%; NS). Subgroup R revealed lower levels of immunoglobulins, especially of IgG4 (p < 0.01) in contrast to patients infected by sensitive bacteria. The innate immunity did not differ significantly between the study groups. Conclusion. Our study showed changes mainly in the adaptive immune system represented by low levels of lymphocyte subpopulations and their memory effector cells, and also changes in humoral immunity in patients with DFUs, even those infected by resistant pathogens, in comparison with diabetic controls. PMID:28050566

  6. Low-level antimicrobial resistance of Enterobacteriaceae isolated from the nares of pig-exposed persons.

    PubMed

    Fischer, J; Hille, K; Mellmann, A; Schaumburg, F; Kreienbrock, L; Köck, R

    2016-03-01

    Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) have recently emerged in livestock and humans. Therefore, this study assessed the carriage of Enterobacteriaceae in the anterior nares and associated antimicrobial resistance in pig-exposed persons. Nasal swabs were enriched in non-selective broth and then plated on MacConkey and ESBL-selective agars. Species was confirmed by matrix-assisted laser-desorption ionization-time-of-flight mass spectrometry (MALDI-ToF MS). Antimicrobial susceptibility testing was performed according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. Of 114 pig-exposed persons tested, Enterobacteriaceae were detected in the nares of 76 (66·7%) participants. The predominant species were Proteus mirabilis (n = 17, 14·9%), Pantoea agglomerans (n = 13, 11·4%), Morganella morganii (n = 9, 7·9%), Citrobacter koseri (n = 9, 7·9%), Klebsiella pneumoniae, Escherichia coli and Proteus vulgaris (each n = 8, 7·0%). ESBL-E were not detected. Of all isolates tested, 3·4% were resistant against ciprofloxacin, 2·3% against gentamicin, 23·9% against trimethoprim-sulfamethoxazole and 44·3% against tigecycline. Despite the high prevalence of ESBL-E in livestock, pig-exposed persons did not carry ESBL-E in their nares. This finding is important, because colonization of the nasal reservoir might cause endogenous infections or facilitate transmission of ESBL-E in the general population.

  7. Type IV resistant starch increases cecum short chain fatty acids level in rats.

    PubMed

    Le Thanh-Blicharz, Joanna; Anioła, Jacek; Kowalczewski, Przemysław; Przygoński, Krzysztof; Zaborowska, Zofia; Lewandowicz, Grażyna

    2014-01-01

    Resistant starches are type of dietary fibers. However, their physiological effects depend on the way they resist digestion in the gastrointestinal tract. The objective of this study was to examine the hypothesis that new type of RS4 preparations, of in vitro digestibility of about 50%, obtained by cross-linking and acetylation, acts as a prebiotic by increasing short chain fatty acids content in cecum digesta. The rats were fed with diet containing pregelatinized, cross-linked and acetylated starches as a main carbohydrate source. Pregelatinized, but not chemically modified, potato starch was used in the composition of the control diet. After two weeks of experiment the increase of short chain fatty acids contents in ceceum digesta was observed. The intake of starch A, cross-linked only with adipic acid, resulted in increase of about 40% of short chain fatty acids content, whereas starch PA cross-linked with sodium trimetaphosphate and adipic acid of about 50%. The utmost twofold increase was observed in the case of the production of propionic acid. In contrast, the content of butyric acid increased (12%) only as an effect of consumption of starch PA and even decreased (about 30%) in case of starch A. Both RS4 starches caused an increase of the production of acetic acid by more than 40%. No changes in serum biochemistry, liver cholesterol and organ weights of rats were stated.

  8. Assessment of the Dominance Level of the R81T Target Resistance to Two Neonicotinoid Insecticides in Myzus persicae (Hemiptera: Aphididae).

    PubMed

    Mottet, Claire; Fontaine, Séverine; Caddoux, Laëtitia; Brazier, Christine; Mahéo, Frédérique; Simon, Jean-Christophe; Micoud, Annie; Roy, Lise

    2016-10-01

    Myzus persicae (Sulzer, 1776), a major crop pest worldwide, displays insecticide resistance to most molecules. The R81T substitution on the β1 subunit of nicotinic receptors of acetylcholine (nAChR) confers target site resistance to neonicotinoids and is widespread in aphid populations colonizing peach tree orchards in Southern Europe. But the impact of this resistance in the field, as well as ways to optimize its management, depends largely on the dominance level of the R81T mutation. In this study, we measured by in vitro assays the response of R81T mutation to two neonicotinoids (imidacloprid and thiacloprid) in 23 M. persicae clones with different resistance genotypes in order to assess the dominance status of this allele. In this study, all homozygous clones for the R81T mutation (genotype 81(TT)) showed a much higher level of resistance to both active substances than other clones. The heterozygous clones 81(RT) displayed a slightly higher level of resistance than wild homozygous, though resistance phenotypes against both neonicotinoids in these two genotypes were overlapping. A great variation of resistance level was found within these two latter clones' categories. The dominance level of insecticide resistance (DLC) strongly suggested that the mutant allele 81T is semirecessive (the wild 81R allele being rather dominant) for both insecticide molecules under test. Mean DLC values were 0.316 for imidacloprid and 0.351 for thiacloprid. Cross-resistance was shown between imidacloprid and thiacloprid. This partial recessivity is valuable information to broaden the knowledge on neonicotinoid resistance, a prerequisite for devising adapted management strategies against insecticide-resistant populations of M. persicae.

  9. Combining COLD-PCR and high-resolution melt analysis for rapid detection of low-level, rifampin-resistant mutations in Mycobacterium tuberculosis.

    PubMed

    Pang, Yu; Liu, Guan; Wang, Yufeng; Zheng, Suhua; Zhao, Yan-Lin

    2013-04-01

    Multidrug-resistant Mycobacterium tuberculosis (M. tuberculosis) remains a serious threat to public health. Mutational analysis of the gene encoding the beta subunit of RNA polymerase (rpoB) is an established and widely used surrogate marker for multidrug-resistant tuberculosis (MDR-TB). The rpoB-based drug-resistant assay requires relatively less time to detect drug resistance in M. tuberculosis, yet it fails to detect low-level mutations in wild-type DNA. Here, we describe a low-level mutation detection method that combines co-amplification at lower denaturation temperature polymerase chain reaction (COLD-PCR) with high-resolution melting (HRM) analysis, aimed at detecting low-level, rifampin-resistant mutations in M. tuberculosis. Compared to conventional polymerase chain reaction (PCR), dilution experiments demonstrated a four- to eightfold improvement in selectivity using COLD-PCR/HRM to detect low-level, rifampin-resistant mutations. The mutation detection limit of conventional PCR/HRM was approximately 20%, whereas COLD-PCR/HRM had a mutation detection limit of 2.5%. Using traditional PCR/HRM and DNA sequencing, we found rpoB mutation in 110 rifampin-resistant isolates. The use of COLD-PCR/HRM allowed us to detect 10 low-level, rifampin-resistant mutations in 16 additional drug-resistant isolates. The sensitivity of COLD-PCR/HRM (95.2%) is significantly higher than that of PCR/HRM (87.3%). Our findings demonstrate that combined use of COLD-PCR with HRM can provide a sensitivity of at least 5% in detecting rpoB-mutated populations in a wild-type background, decreasing the delay in drug-resistant TB diagnosis and leading to faster, cheaper, more efficient, and more personalized antibiotic treatment, especially for low-level drug resistance mutations among the excess wild-type DNA.

  10. Characterization of high fluence neutron induced defect levels in high resistivity silicon detectors using a laser deep level transient spectroscopy (L-DLTS)

    NASA Astrophysics Data System (ADS)

    Chengji, Li; Li, Zheng

    1994-03-01

    Neutron irradiated high resistivity (4-6 kΩ-cm) silicon detectors in the neutron fluence ( Φn) range of 5 × 10 11 n/cm 2 to 1 × 10 14 n/cm 2 have been studied using a laser deep level transient spectroscopy (L-DLTS). It has been found that the A-center (oxygen-vacancy, Ec = 0.17 eV) concentration increases with neutron fluence, reaching a maximum at Φn ≈ 5×10 12 n/cm 2 before decreasing with Φn. A broad peak has been found between 200 K and 300 K, which is the result of the overlap of three single levels: the V-V - ( Ec = 0.38 eV), the E-center (P-v, Ec = 0.44 eV), and a level at Ec = 0.56 eV that is probably V-V 0. At low neutron fluences ( Φn < 5 × 10 12 n/cm 2), this broad peak is dominated by V-V - and the E-centers. However, as the fluence increases ( Φn ≥ 5 × 10 12 n/cm 2), the peak becomes dominated by the level of Ec = 0.56 eV.

  11. Research on a Defects Detection Method in the Ferrite Phase Shifter Cementing Process Based on a Multi-Sensor Prognostic and Health Management (PHM) System

    PubMed Central

    Wan, Bo; Fu, Guicui; Li, Yanruoyue; Zhao, Youhu

    2016-01-01

    The cementing manufacturing process of ferrite phase shifters has the defect that cementing strength is insufficient and fractures always appear. A detection method of these defects was studied utilizing the multi-sensors Prognostic and Health Management (PHM) theory. Aiming at these process defects, the reasons that lead to defects are analyzed in this paper. In the meanwhile, the key process parameters were determined and Differential Scanning Calorimetry (DSC) tests during the cure process of resin cementing were carried out. At the same time, in order to get data on changing cementing strength, multiple-group cementing process tests of different key process parameters were designed and conducted. A relational model of cementing strength and cure temperature, time and pressure was established, by combining data of DSC and process tests as well as based on the Avrami formula. Through sensitivity analysis for three process parameters, the on-line detection decision criterion and the process parameters which have obvious impact on cementing strength were determined. A PHM system with multiple temperature and pressure sensors was established on this basis, and then, on-line detection, diagnosis and control for ferrite phase shifter cementing process defects were realized. It was verified by subsequent process that the on-line detection system improved the reliability of the ferrite phase shifter cementing process and reduced the incidence of insufficient cementing strength defects. PMID:27517935

  12. A wideband 360° photonic-assisted microwave phase shifter using a polarization modulator and a polarization-maintaining fiber Bragg grating.

    PubMed

    Li, Wangzhe; Zhang, Weifeng; Yao, Jianping

    2012-12-31

    A novel approach to implementing a wideband microwave photonic phase shifter by a joint use of a polarization modulator (PolM) and a polarization-maintaining fiber Bragg grating (PM-FBG) is proposed and experimentally demonstrated. A microwave signal to be phase shifted is applied to the PolM. Two phase-modulated signals along the two principal axes of the PolM are generated and sent to the PM-FBG. The phase-modulated signals have a static but complementary phase shift introduced by the dc bias applied to the PolM. Due to the birefringence of the polarization-maintaining (PM) fiber, the PM-FBG has two spectrally separated and orthogonally polarized reflection bands. By employing the PM-FBG to reflect one first-order sideband along one polarization direction and one optical carrier along the other polarization direction, and send them back to the PolM, a second-time phase modulation is imposed to the sideband and the optical carrier. By sending the two signals to a polarizer and beating them at a photodetector, a phase shifted microwave signal is obtained. Since the PolM is used twice, a low dc bias voltage would lead to a large phase shift. A full 360° microwave photonic phase shifter over a frequency range of 30-40 GHz is experimentally demonstrated. The spurious free dynamic range (SFDR) of the phase shifter is also studied.

  13. Research on a Defects Detection Method in the Ferrite Phase Shifter Cementing Process Based on a Multi-Sensor Prognostic and Health Management (PHM) System.

    PubMed

    Wan, Bo; Fu, Guicui; Li, Yanruoyue; Zhao, Youhu

    2016-08-10

    The cementing manufacturing process of ferrite phase shifters has the defect that cementing strength is insufficient and fractures always appear. A detection method of these defects was studied utilizing the multi-sensors Prognostic and Health Management (PHM) theory. Aiming at these process defects, the reasons that lead to defects are analyzed in this paper. In the meanwhile, the key process parameters were determined and Differential Scanning Calorimetry (DSC) tests during the cure process of resin cementing were carried out. At the same time, in order to get data on changing cementing strength, multiple-group cementing process tests of different key process parameters were designed and conducted. A relational model of cementing strength and cure temperature, time and pressure was established, by combining data of DSC and process tests as well as based on the Avrami formula. Through sensitivity analysis for three process parameters, the on-line detection decision criterion and the process parameters which have obvious impact on cementing strength were determined. A PHM system with multiple temperature and pressure sensors was established on this basis, and then, on-line detection, diagnosis and control for ferrite phase shifter cementing process defects were realized. It was verified by subsequent process that the on-line detection system improved the reliability of the ferrite phase shifter cementing process and reduced the incidence of insufficient cementing strength defects.

  14. High level of cross-resistance between kanamycin, amikacin, and capreomycin among Mycobacterium tuberculosis isolates from Georgia and a close relation with mutations in the rrs gene.

    PubMed

    Jugheli, Levan; Bzekalava, Nino; de Rijk, Pim; Fissette, Krista; Portaels, Françoise; Rigouts, Leen

    2009-12-01

    The aminoglycosides kanamycin and amikacin and the macrocyclic peptide capreomycin are key drugs for the treatment of multidrug-resistant tuberculosis (MDR-TB). The increasing rates of resistance to these drugs and the possible cross-resistance between them are concerns for MDR-TB therapy. Mutations in the 16S rRNA gene (rrs) have been associated with resistance to each of the drugs, and mutations of the tlyA gene, which encodes a putative rRNA methyltransferase, are thought to confer capreomycin resistance in Mycobacterium tuberculosis bacteria. Studies of possible cross-resistance have shown variable results. In this study, the MICs of these drugs for 145 clinical isolates from Georgia and the sequences of the rrs and tlyA genes of the isolates were determined. Of 78 kanamycin-resistant strains, 9 (11.5%) were susceptible to amikacin and 16 (20.5%) were susceptible to capreomycin. Four strains were resistant to capreomycin but were susceptible to the other drugs, whereas all amikacin-resistant isolates were resistant to kanamycin. Sequencing revealed six types of mutations in the rrs gene (A514C, C517T, A1401G, C1402T, C1443G, T1521C) but no mutations in the tlyA gene. The A514C, C517T, C1443G, and T1521C mutations showed no association with resistance to any of the drugs. The A1401G and C1402T mutations were observed in 65 kanamycin-resistant isolates and the 4 capreomycin-resistant isolates, respectively, whereas none of the susceptible isolates showed either of those mutations. The four mutants with the C1402T mutations showed high levels of resistance to capreomycin but no resistance to kanamycin and amikacin. Detection of the A1401G mutation appeared to be 100% specific for the detection of resistance to kanamycin and amikacin, while the sensitivities reached 85.9% and 94.2%, respectively.

  15. The effect of vitamin D replacement therapy on insulin resistance and androgen levels in women with polycystic ovary syndrome.

    PubMed

    Selimoglu, H; Duran, C; Kiyici, S; Ersoy, C; Guclu, M; Ozkaya, G; Tuncel, E; Erturk, E; Imamoglu, S

    2010-04-01

    Insulin resistance (IR) is one of the common features of the polycystic ovary syndrome (PCOS), and recent studies indicate the possible role of vitamin D in the pathogenesis of IR and glucose metabolism. Aim of this study was aimed to determine the effect of vitamin D replacement therapy on glucose metabolism, insulin, and androgen levels in obese, insulin-resistant women with PCOS. Eleven women with PCOS were included in the study. Mean age of the patients was 23.6+/-5.7 yr, body mass index 33.9+/-5.1 kg/m(2). Six patients (54.5%) had acantosis nigricans and 10 (90.9%) oligoamenorrhea. The mean Ferriman Gallwey score was 14.1+/-4.6. Only 2 women were within the normal limits of vitamin D levels as >20 ng/ml. Three weeks after the administration of the single dose of 300,000 units of vitamin D3 orally, 25-hydroxyvitamin D3 significantly increased from 16.9+/-16 ng/ml to 37.1+/-14.6 ng/ml (p: 0.027) and only 2 women were detected to have vitamin D3 levels <20 ng/ml. Although glucose and insulin levels were decreased non-significantly, homeostasis model assessment (HOMA)-IR significantly decreased from 4.41+/-1.38 to 3.67+/-1.48 (p: 0.043). No significant alterations were witnessed at the levels of DHEAS, total and free testosterone, androstenedione. No correlation was found between vitamin D with HOMA and other hormonal parameters. In conclusion, women with PCOS have mostly insufficient vitamin D levels, and vitamin D replacement therapy may have a beneficial effect on IR in obese women with PCOS.

  16. Relationship between Serum Levels of Body Iron Parameters and Insulin Resistance and Metabolic Syndrome in Korean Children

    PubMed Central

    Lee, Hye-Ja; Jang, Han Byul; Park, Ji Eun; Park, Kyung-Hee; Kang, Jae Heon; Park, Sang Ick; Song, Jihyun

    2014-01-01

    Objectives An increase in serum ferritin and levels of the cleaved soluble form of transferrin receptor (sTfR) are related to several metabolic conditions. We evaluated the relationship between body iron status indicators, including ferritin and sTfR, and insulin resistance and metabolic syndrome (MetS) in Korean children. Methods A cross-sectional study was conducted on 1350 children in Korea. Anthropometrical parameters; lipid profiles; levels of glucose, insulin, and leptin; and iron status indicators, including sTfR, serum ferritin, serum iron, total iron-binding capacity (TIBC), and transferrin saturation (TS), were analyzed. Results Although serum sTfR levels were significantly higher in boys than in girls (2.20 vs. 2.06 mg/L, p < 0.0001), serum iron and TS were higher in girls than in boys (101.38 vs. 95.77 mg/L, p = 0.027 and 30.15 vs. 28.91%, p = 0.04, respectively). Waist circumference (WC) and leptin were most significantly associated with body iron indicators when adjusted for age and sex. After adjusting for age, sex, and WC, sTfR levels showed the strongest positive association with leptin levels (p = 0.0001). Children in the highest tertile for homeostasis model assessment-insulin resistance (HOMA-IR) had higher TIBC (p = 0.0005) and lower serum iron (p = 0.0341), and the lowest TS (p < 0.0001) after adjustment for confounders. Children with higher sTfR were most significantly associated with risk of MetS compared with those lower sTfR (p = 0.0077). Conclusion The associations of serum levels of iron metabolism markers with leptin levels, HOMA-IR, and MetS suggest that iron-related factors may involve insulin resistance and MetS. PMID:25379371

  17. Increased basal level of Akt-dependent insulin signaling may be responsible for the development of insulin resistance

    PubMed Central

    Liu, Hui-Yu; Hong, Tao; Wen, Ge-Bo; Han, Jianmin; Zuo, Degen; Liu, Zhenqi

    2009-01-01

    A majority of subjects with insulin resistance and hyperinsulinemia can maintain their blood glucose levels normal for the whole life presumably through protein kinase B (Akt)-dependent insulin signaling. In this study, we found that the basal Akt phosphorylation level was increased in liver and gastrocnemius of mice under the high-fat diet (HFD). Levels of mitochondrial DNA and expression of some mitochondrion-associated genes were decreased by the HFD primarily in liver. Triglyceride content was increased in both liver and gastrocnemius by the HFD. Oxidative stress was induced by the HFD in both liver and gastrocnemius. Insulin sensitivity was decreased by the HFD. All of these changes were largely or completely reversed by treatment of animals with the phosphatidylinositol 3-kinase inhibitor LY-294002 during the time when animals usually do not eat. Consequently, the overall insulin sensitivity was increased by treatment with LY-294002. Together, our results indicate that increased basal Akt-dependent insulin signaling suppresses mitochondrial production, increases ectopic fat accumulation, induces oxidative stress, and desensitizes insulin signaling in subjects with insulin resistance and hyperinsulinemia. PMID:19638508

  18. Overexpression of Rad in muscle worsens diet-induced insulin resistance and glucose intolerance and lowers plasma triglyceride level

    NASA Astrophysics Data System (ADS)

    Ilany, Jacob; Bilan, Philip J.; Kapur, Sonia; Caldwell, James S.; Patti, Mary-Elizabeth; Marette, Andre; Kahn, C. Ronald

    2006-03-01

    Rad is a low molecular weight GTPase that is overexpressed in skeletal muscle of some patients with type 2 diabetes mellitus and/or obesity. Overexpression of Rad in adipocytes and muscle cells in culture results in diminished insulin-stimulated glucose uptake. To further elucidate the potential role of Rad in vivo, we have generated transgenic (tg) mice that overexpress Rad in muscle using the muscle creatine kinase (MCK) promoter-enhancer. Rad tg mice have a 6- to 12-fold increase in Rad expression in muscle as compared to wild-type littermates. Rad tg mice grow normally and have normal glucose tolerance and insulin sensitivity, but have reduced plasma triglyceride levels. On a high-fat diet, Rad tg mice develop more severe glucose intolerance than the wild-type mice; this is due to increased insulin resistance in muscle, as exemplified by a rightward shift in the dose-response curve for insulin stimulated 2-deoxyglucose uptake. There is also a unexpected further reduction of the plasma triglyceride levels that is associated with increased levels of lipoprotein lipase in the Rad tg mice. These results demonstrate a potential synergistic interaction between increased expression of Rad and high-fat diet in creation of insulin resistance and altered lipid metabolism present in type 2 diabetes. diabetes mellitus | glucose transport | RGK GTPase | transgenic mouse

  19. Improved multi-level capability in Si3N4-based resistive switching memory using continuous gradual reset switching

    NASA Astrophysics Data System (ADS)

    Kim, Sungjun; Park, Byung-Gook

    2017-01-01

    In this letter, we compare three different types of reset switching behavior in a bipolar resistive random-access memory (RRAM) system that is housed in a Ni/Si3N4/Si structure. The abrupt, step-like gradual and continuous gradual reset transitions are largely determined by the low-resistance state (LRS). For abrupt reset switching, the large conducting path shows ohmic behavior or has a weak nonlinear current-voltage (I-V) characteristics in the LRS. For gradual switching, including both the step-like and continuous reset types, trap-assisted direct tunneling is dominant in the low-voltage regime, while trap-assisted Fowler-Nordheim tunneling is dominant in the high-voltage regime, thus causing nonlinear I-V characteristics. More importantly, we evaluate the multi-level capabilities of the two different gradual switching types, including both step-like and continuous reset behavior, using identical and incremental voltage conditions. Finer control of the conductance level with good uniformity is achieved in continuous gradual reset switching when compared to that in step-like gradual reset switching. For continuous reset switching, a single conducting path, which initially has a tunneling gap, gradually responds to pulses with even and identical amplitudes, while for step-like reset switching, the multiple conducting paths only respond to incremental pulses to obtain effective multi-level states.

  20. Can Resistance Exercise Alter Irisin Levels and Expression Profiles of FNDC5 and UCP1 in Rats?

    PubMed Central

    Reisi, Jalil; Ghaedi, Kamran; Rajabi, Hamid; Marandi, Sayyed Mohammad

    2016-01-01

    Background Irisin is a new myokine secreted from the skeletal muscle and appears to affect the metabolism of adipose tissue. Objectives The mechanisms of cellular and molecular identification by which exercise training exerts its benefits remain unclear and are under investigation. Methods We examined the effect of 8-week resistance exercise on plasma irisin levels and expression profiles of muscle FNDC5 and subcutaneous adipose tissue UCP1 in male rats. Sixteen adult male rats were divided into two groups, control (n = 8) and exercise training (n = 8) groups. The training group received exercise for 3 days/week on a specific ladder (120 cm height) with a carrying load of 50% of body weight, which was attached to their tails. Results The weight of the load was gradually increased during the training sessions, ultimately reaching 200% of the body weight of rats in the final week. There were three sets of five repetitions with a 3-min rest between each set of exercise sessions and 1 minute between repetitions. Plasma irisin levels and relative mRNA expression of the genes UCP1 and FNDC5 were assessed. The results demonstrated a significant increase in the irisin levels after 8 weeks of resistance exercise (P < 0.001, t = 4.48). The relative expression of FNDC5 (P < 0.001, t = 6.18) and UCP1 genes (P < 0.001, t = 13.91) was also significantly increased. Conclusions Therefore, we can conclude from this study that resistance exercise may improve body composition possibly through increased thermogenesis in white adipose tissue through the secretion of irisin. PMID:28144410

  1. The science behind codes and standards for safe walkways: changes in level, stairways, stair handrails and slip resistance.

    PubMed

    Nemire, Kenneth; Johnson, Daniel A; Vidal, Keith

    2016-01-01

    Walkway codes and standards are often created through consensus by committees based on a number of factors, including historical precedence, common practice, cost, and empirical data. The authors maintain that in the formulation of codes and standards that impact pedestrian safety, the results of pertinent scientific research should be given significant weight. This article examines many elements of common walkway codes and standards related to changes in level, stairways, stair handrails, and slip resistance. It identifies which portions are based on or supported by empirical data; and which could benefit from additional scientific research. This article identifies areas in which additional research, codes, and standards may be beneficial to enhance pedestrian safety.

  2. [Peculiarities of cardiovascular syndrome in children and adolescents with obesity in dependence of level of insulin resistance].

    PubMed

    Bekezin, V V; Kozlova, L V; Kozlova, I S; Igolkina, M V

    2008-01-01

    We conducted complex study of the state of cardiovascular system in 157 children aged 11-16 years with I-III degree obesity. Dazing on the results it is suggested to include in cardiovascular syndrome in children with obesity together with arterial hypertension syndrome of vegetative (autonomic) dysfunction, manifesting by disturbance of heart rate variability, endothelial dysfunction as well as systolic-diastolic dysfunction of the left ventricle. Degree of severity of impairment of cardiovascular system in children and adolescents with obesity depends on the level of insulin resistance.

  3. Interference in Pheromone-Responsive Conjugation of a High-Level Bacitracin Resistant Enterococcus faecalis Plasmid of Poultry Origin

    PubMed Central

    Tremblay, Cindy-Love; Archambault, Marie

    2013-01-01

    The current study reports on contact interference of a high-level bacitracin- resistant pheromone-responsive plasmid of Enterococcus faecalis strain 543 of poultry origin during conjugative transfer of bcr antimicrobial resistance genes using a polyclonal antiserum aggregation substance44–560 (AS). After induction with pheromones produced by the recipient strain E. faecalis JH2-2, clumping of the donor E. faecalis strain 543 was observed as well as high transfer frequencies of bcr in short time broth mating. Filter mating assays from donor strain E. faecalis 543 to the recipient strain E. faecalis JH2-2 revealed conjugative transfer of asa1 (AS), bcrRAB and traB (negative regulator pheromone response) genes. The presence of these genes in transconjugants was confirmed by antimicrobial susceptibility testing, PCR, Southern hybridization and sequencing. A significant reduction in formation of aggregates was observed when the polyclonal anti-AS44–560 was added in the pheromone-responsive conjugation experiments as compared to the induced state. Moreover, interference of anti-AS44–560 antibodies in pheromone-responsive conjugation was demonstrated by a reduction in horizontal transfer of asa1 and bcr genes between E. faecalis strain 543 and E. faecalis JH2-2. Reducing the pheromone-responsive conjugation of E. faecalis is of interest because of its clinical importance in the horizontal transfer of antimicrobial resistance. PMID:24030654

  4. High-level carbapenem-resistant OXA-48-producing Klebsiella pneumoniae with a novel OmpK36 variant and low-level, carbapenem-resistant, non-porin-deficient, OXA-181-producing Escherichia coli from Thailand.

    PubMed

    Lunha, Kamonwan; Chanawong, Aroonwadee; Lulitanond, Aroonlug; Wilailuckana, Chotechana; Charoensri, Nicha; Wonglakorn, Lumyai; Saenjamla, Pimjai; Chaimanee, Prajuab; Angkititrakul, Sunpetch; Chetchotisakd, Ploenchan

    2016-06-01

    Five blaOXA-48-like-carrying Enterobacteriaceae isolates collected from two Thai patients in December 2012 were characterized. Three Klebsiella pneumoniae isolates giving two different pulsed-field gel electrophoresis patterns and sequence types (ST11 and ST37) from patient 1 harbored blaOXA-48 locating on Tn1999.2, whereas two Escherichia coli isolates with the same pulsotype and ST5 from Patient 2 carried ISEcp1-associated blaOXA-181. One K. pneumoniae strain had blaSHV-12, blaDHA-1, qnrB, and qnrS, while another strain harbored blaCTX-M-15, qnrS and aac(6')-Ib-cr. The E. coli strain contained blaCTX-M-15, blaCMY-2, qnrS, and aac(6')-Ib-cr. Interestingly, the OXA-48 producers with a novel OmpK36 variant by a substitution of Gly to Asp in the L3 loop-borne PEFXG motif exhibited high-level resistance to ertapenem, imipenem, and meropenem. In contrast, the OXA-181 producer with non-porin-deficient background showed low-level resistance to ertapenem only. Both patients died because of either septic shock or pneumonia. This study showed the impact of OXA-48-like carbapenemases in porin-defective clinical isolate background, which may lead to serious therapeutic problems in the near future.

  5. Effects of acute resistance exercise on acyl-ghrelin and obestatin levels in hemodialysis patients: a pilot study.

    PubMed

    Moraes, Cristiane; Borges, Natália A; Barboza, Jorge; Barros, Amanda F; Mafra, Denise

    2015-11-01

    Chronic physical exercises may be beneficial to modulate appetite hormones as acyl-ghrelin (orexigenic) and obestatin (anorexigenic) in chronic kidney disease (CKD) patients; however, there are no data about the effects of acute exercises on these hormones. Thus, the aim of the present study was to assess the effect of acute resistance exercise on appetite hormones (acyl-ghrelin and obestatin) of patients undergoing hemodialysis (HD). Twenty-five patients (44.7 ± 12.9 years, 68% women) on regular HD program were enrolled into two groups, 16 patients performed exercises and 9 patients comprised the control group. The patients performed the exercises in both lower limbs with ankle-cuffs and elastic bands, 30 min after the initiation of hemodialysis session. Blood samples of both the groups were drawn in the morning before and after 30 min with exercise session (exercise group) and, before and after the same time without exercise (control group). Acyl-ghrelin and obestatin plasma levels were measured using an enzyme immunometric assay. Acyl-ghrelin plasma levels did not change in both the groups. However, when stratified by gender the acyl-ghrelin increased significantly right after exercise in men [32.1 pg/mL (25.6-41.2) to 46.0 pg/mL (39.0-59.5)] (p = 0.04). Obestatin plasma levels reduced after a single bout of exercise and changes remained significantly when the sample was stratified by gender. There was no change in obestatin plasma levels in control group. A single bout of resistance exercise seems to modulate the levels of appetite hormones in HD patients.

  6. Penicillin-Binding Protein Transpeptidase Signatures for Tracking and Predicting β-Lactam Resistance Levels in Streptococcus pneumoniae

    PubMed Central

    Metcalf, Benjamin J.; Chochua, Sopio; Li, Zhongya; Gertz, Robert E.; Walker, Hollis; Hawkins, Paulina A.; Tran, Theresa; Whitney, Cynthia G.; McGee, Lesley; Beall, Bernard W.

    2016-01-01

    ABSTRACT β-Lactam antibiotics are the drugs of choice to treat pneumococcal infections. The spread of β-lactam-resistant pneumococci is a major concern in choosing an effective therapy for patients. Systematically tracking β-lactam resistance could benefit disease surveillance. Here we developed a classification system in which a pneumococcal isolate is assigned to a “PBP type” based on sequence signatures in the transpeptidase domains (TPDs) of the three critical penicillin-binding proteins (PBPs), PBP1a, PBP2b, and PBP2x. We identified 307 unique PBP types from 2,528 invasive pneumococcal isolates, which had known MICs to six β-lactams based on broth microdilution. We found that increased β-lactam MICs strongly correlated with PBP types containing divergent TPD sequences. The PBP type explained 94 to 99% of variation in MICs both before and after accounting for genomic backgrounds defined by multilocus sequence typing, indicating that genomic backgrounds made little independent contribution to β-lactam MICs at the population level. We further developed and evaluated predictive models of MICs based on PBP type. Compared to microdilution MICs, MICs predicted by PBP type showed essential agreement (MICs agree within 1 dilution) of >98%, category agreement (interpretive results agree) of >94%, a major discrepancy (sensitive isolate predicted as resistant) rate of <3%, and a very major discrepancy (resistant isolate predicted as sensitive) rate of <2% for all six β-lactams. Thus, the PBP transpeptidase signatures are robust indicators of MICs to different β-lactam antibiotics in clinical pneumococcal isolates and serve as an accurate alternative to phenotypic susceptibility testing. PMID:27302760

  7. Performance analysis on quality of optical frequency comb generated by the recirculating frequency shifter based on linear IQ modulator

    NASA Astrophysics Data System (ADS)

    Sun, Lu; Li, Jianping; Lin, Jiachuan; Xi, Lixia; Tang, Xianfeng; Zhang, Xiaoguang

    2015-11-01

    An optical frequency comb generator using a modified single-sideband recirculating frequency shifter scheme adopting a linear IQ modulator as the kernel device (SSB-RFS-LIQM) is proposed. The optical comb lines generated by the proposed scheme possess good features such as extreme flatness and high optical signal-to-noise ratio (OSNR), compared to the quality we can obtain when we use a conventional IQ modulator in the SSB-RFS structure (called SSB-RFS-CIQM scheme). The mechanism of how the SSB-RFS-LIQM works is carefully analyzed with analytical and numerical methods. With the capability of strong suppression of high-order crosstalk and less demand of the gain of erbium-doped fiber amplifiers (and hence less amplified spontaneous noise induced) in the loop, 5.5 dB OSNR improvement can be achieved when 100 extreme flat comb lines are generated using the SSB-RFS-LIQM scheme compared to using the SSB-RFS-CIQM scheme.

  8. High-Precision Time Delay Control with Continuous Phase Shifter for Pump-Probe Experiments Using Synchrotron Radiation Pulses

    SciTech Connect

    Tanaka, Yoshihito; Ohshima, Takashi; Moritomo, Yutaka; Tanaka, Hitoshi; Takata, Masaki

    2010-06-23

    Brilliant pulsed x-ray synchrotron radiation (SR) is useful for pump-probe experiment such as time-resolved x-ray diffraction, x-ray absorption fine structure, and x-ray spectroscopy. For laser pump-SR x-ray probe experiments, short pulsed lasers are generally synchronized to the SR master oscillator controlling the voltage for acceleration of electron bunches in an accelerator, and the interval between the laser and the SR pulses is changed around the time scale of target phenomenon. Ideal delay control produces any time delay as keeping the time-precision and pointing-stability of optical pulses at a sample position. We constructed the time delay control module using a continuous phase shifter of radio frequency signal and a frequency divider, which can produce the delayed trigger pulses to the laser without degradation of the time precision and the pointing stability. A picoseconds time-resolved x-ray diffraction experiment was demonstrated at SPring-8 storage ring for fast lattice response by femtosecond pulsed laser irradiation, and suggested the possibility of accurate sound velocity measurement. A delay control unit operating with subpicosecond precision has also been designed for femtosecond pump-probe experiments using a free electron laser at SPring-8 campus.

  9. Monte Carlo code G3sim for simulation of plastic scintillator detectors with wavelength shifter fiber readout

    NASA Astrophysics Data System (ADS)

    Mohanty, P. K.; Dugad, S. R.; Gupta, S. K.

    2012-04-01

    A detailed description of a compact Monte Carlo simulation code "G3sim" for studying the performance of a plastic scintillator detector with wavelength shifter (WLS) fiber readout is presented. G3sim was developed for optimizing the design of new scintillator detectors used in the GRAPES-3 extensive air shower experiment. Propagation of the blue photons produced by the passage of relativistic charged particles in the scintillator is treated by incorporating the absorption, total internal, and diffuse reflections. Capture of blue photons by the WLS fibers and subsequent re-emission of longer wavelength green photons is appropriately treated. The trapping and propagation of green photons inside the WLS fiber is treated using the laws of optics for meridional and skew rays. Propagation time of each photon is taken into account for the generation of the electrical signal at the photomultiplier. A comparison of the results from G3sim with the performance of a prototype scintillator detector showed an excellent agreement between the simulated and measured properties. The simulation results can be parametrized in terms of exponential functions providing a deeper insight into the functioning of these versatile detectors. G3sim can be used to aid the design and optimize the performance of scintillator detectors prior to actual fabrication that may result in a considerable saving of time, labor, and money spent.

  10. Effects of Noise Exposure on Systemic and Tissue-Level Markers of Glucose Homeostasis and Insulin Resistance in Male Mice

    PubMed Central

    Liu, Lijie; Wang, Fanfan; Lu, Haiying; Cao, Shuangfeng; Du, Ziwei; Wang, Yongfang; Feng, Xian; Gao, Ye; Zha, Mingming; Guo, Min; Sun, Zilin; Wang, Jian

    2016-01-01

    Background: Epidemiological studies have indicated that noise exposure is associated with an increased risk of type 2 diabetes mellitus (T2DM). However, the nature of the connection between noise exposure and T2DM remains to be explored. Objectives: We explored whether and how noise exposure affects glucose homeostasis in mice as the initial step toward T2DM development. Methods: Male ICR mice were randomly assigned to one of four groups: the control group and three noise groups (N20D, N10D, and N1D), in which the animals were exposed to white noise at 95 decibel sound pressure level (dB SPL) for 4 hr per day for 20 successive days, 10 successive days, or 1 day, respectively. Glucose tolerance and insulin sensitivity were evaluated 1 day, 1 week, and 1 month after the final noise exposure (1DPN, 1WPN, and 1MPN). Standard immunoblots, immunohistochemical methods, and enzyme-linked immunosorbent assays (ELISA) were performed to assess insulin signaling in skeletal muscle, the morphology of β cells, and plasma corticosterone levels. Results: Noise exposure for 1 day caused transient glucose intolerance and insulin resistance, whereas noise exposure for 10 and 20 days had no effect on glucose tolerance but did cause prolonged insulin resistance and an increased insulin response to glucose challenge. Akt phosphorylation and GLUT4 translocation in response to exogenous insulin were decreased in the skeletal muscle of noise-exposed animals. Conclusions: Noise exposure at 95 dB SPL caused insulin resistance in male ICR mice, which was prolonged with longer noise exposure and was likely related to the observed blunted insulin signaling in skeletal muscle. Citation: Liu L, Wang F, Lu H, Cao S, Du Z, Wang Y, Feng X, Gao Y, Zha M, Guo M, Sun Z, Wang J. 2016. Effects of noise exposure on systemic and tissue-level markers of glucose homeostasis and insulin resistance in male mice. Environ Health Perspect 124:1390–1398; http://dx.doi.org/10.1289/EHP162 PMID:27128844

  11. Oxidative stress, glutathione level and antioxidant response to heavy metals in multi-resistant pathogen, Candida tropicalis.

    PubMed

    Ilyas, Sidra; Rehman, Abdul

    2015-01-01

    In this study, we explored the multiple heavy metal-resistant yeast isolated from heavy metal-polluted environment. The isolated yeast showed maximum growth at 30 °C, pH 7.0, and the strain was identified as Candida tropicalis through 18S ribosomal RNA (rRNA) gene sequence analysis. Yeast cells grew well in medium containing different concentrations of heavy metal ions [CdCl₂, Pb(NO₃)₂, NaAsO₂, CuSO₄ and K₂Cr₂O₇]. Minimum inhibitory concentration (MIC) against different metal ions was ranged from 5 to 19 mM, and the metal resistance value against each metal observed by yeast cells was 5 mM (Cr), 10 mM (Cd), 15 mM (As), 14 mM (Cu) and 19 mM (Pb) and increased in the following order: Pb > Cu > As ≥ Cd > Cr. The total cellular glutathione, GSH/GSSG redox couple and metallothioneins like protein (MT) were assayed by growing cultures for 24 h and exposed to 100 mg/L of each heavy metal ion. Remarkable increase in γ-glutamylcysteinylglycine (GSH) level was determined in arsenic and cadmium treatment followed by chromium, lead and copper. Stressed cells had much more oxidized GSH than unstressed cells. GSH/GSSG ratio was significantly increased in cadmium and copper treatment in contrast to chromium, arsenic and lead. Statistical analysis revealed significantly higher cysteine level in all metal-treated samples as compared to control. Antioxidant glutathione transferase activity was not detected in metal-treated and untreated yeast samples. One-dimensional electrophoresis of proteins revealed marked differences in banding pattern of heavy metal-exposed yeast samples. A prominent 20 kDa band was observed in all treated samples suggesting that some differential proteins could be over-expressed during heavy metal treatment and might be involved in cell resistance mechanisms.

  12. Lithium and Valproate Levels Do Not Correlate with Ketamine's Antidepressant Efficacy in Treatment-Resistant Bipolar Depression.

    PubMed

    Xu, Annie J; Niciu, Mark J; Lundin, Nancy B; Luckenbaugh, David A; Ionescu, Dawn F; Richards, Erica M; Vande Voort, Jennifer L; Ballard, Elizabeth D; Brutsche, Nancy E; Machado-Vieira, Rodrigo; Zarate, Carlos A

    2015-01-01

    Ketamine and lithium both inhibit glycogen synthase kinase 3. In addition, lithium and ketamine have synergistic antidepressant-like effects at individually subeffective doses in rodents. We hypothesized that ketamine's antidepressant effects would be improved by therapeutic doses of lithium versus valproate and that serum lithium levels would positively correlate with ketamine's antidepressant efficacy. Thirty-six patients with treatment-resistant bipolar depression maintained on therapeutic-dose lithium (n = 23, 0.79 ± 0.15 mEq/L) or valproate (n = 13, 79.6 ± 12.4 mg/mL) received 0.5 mg/kg ketamine infusion in a randomized, double-blind, placebo-controlled, crossover trial. The primary depression outcome measure-the Montgomery-Åsberg Depression Rating Scale (MADRS)-was assessed before infusion and at numerous postinfusion time points. Both lithium (F 1,118 = 152.08, p < 0.001, and d = 2.27) and valproate (F 1,128 = 20.12, p < 0.001, and d = 0.79) significantly improved depressive symptoms, but no statistically significant difference was observed between mood stabilizer groups (F 1,28 = 2.51, p = 0.12, and d = 0.60). Serum lithium and valproate levels did not correlate with ketamine's antidepressant efficacy. Although the study was potentially underpowered, our results suggest that lithium may not potentiate ketamine's antidepressant efficacy in treatment-resistant bipolar depression.

  13. High-level expression of alternative oxidase protein sequences enhances the spread of viral vectors in resistant and susceptible plants.

    PubMed

    Murphy, Alex M; Gilliland, Androulla; York, Caroline J; Hyman, Belinda; Carr, John P

    2004-12-01

    The alternative oxidase (AOX) is the terminal oxidase of the cyanide-resistant alternative respiratory pathway in plants and has been implicated in resistance to viruses. When tobacco mosaic virus (TMV) vectors were used to drive very high levels of expression of either AOX or AOX mutated in its active site (AOX-E), virus spread was enhanced. This was visualized as the induction of larger hypersensitive-response lesions after inoculation onto NN-genotype tobacco than those produced by vectors bearing sequences of comparable length [the green fluorescent protein (gfp) gene sequence or antisense aox] or the 'empty' viral vector. Also, in the highly susceptible host Nicotiana benthamiana, systemic movement of TMV vectors expressing AOX or AOX-E was faster than that of TMV constructs bearing gfp or antisense aox sequences. Notably, in N. benthamiana, TMV.AOX and TMV.AOX-E induced symptoms that were severe and ultimately included cell death, whereas the empty vector, TMV.GFP and the TMV vector expressing antisense aox sequences never induced necrosis. The results show that, if expressed at sufficiently high levels, active and inactive AOX proteins can affect virus spread and symptomology in plants.

  14. Mature-stem expression of a silencing-resistant sucrose isomerase gene drives isomaltulose accumulation to high levels in sugarcane.

    PubMed

    Mudge, Stephen R; Basnayake, Shiromi W V; Moyle, Richard L; Osabe, Kenji; Graham, Michael W; Morgan, Terence E; Birch, Robert G

    2013-05-01

    Isomaltulose (IM) is a natural isomer of sucrose. It is widely approved as a food with properties including slower digestion, lower glycaemic index and low cariogenicity, which can benefit consumers. Availability is currently limited by the cost of fermentative conversion from sucrose. Transgenic sugarcane plants with developmentally-controlled expression of a silencing-resistant gene encoding a vacuole-targeted IM synthase were tested under field conditions typical of commercial sugarcane cultivation. High yields of IM were obtained, up to 483 mm or 81% of total sugars in whole-cane juice from plants aged 13 months. Using promoters from sugarcane to drive expression preferentially in the sugarcane stem, IM levels were consistent between stalks and stools within a transgenic line and across consecutive vegetative field generations of tested high-isomer lines. Germination and early growth of plants from setts were unaffected by IM accumulation, up to the tested level around 500 mm in flanking stem internodes. These are the highest yields ever achieved of value-added materials through plant metabolic engineering. The sugarcane stem promoters are promising for strategies to achieve even higher IM levels and for other applications in sugarcane molecular improvement. Silencing-resistant transgenes are critical to deliver the potential of these promoters in practical sugarcane improvement. At the IM levels now achieved in field-grown sugarcane, direct production of IM in plants is feasible at a cost approaching that of sucrose, which should make the benefits of IM affordable on a much wider scale.

  15. Leptin resistance is not the primary cause of weight gain associated with reduced sex hormone levels in female mice.

    PubMed

    da Silva, Regina P; Zampieri, Thais T; Pedroso, João A B; Nagaishi, Vanessa S; Ramos-Lobo, Angela M; Furigo, Isadora C; Câmara, Niels O; Frazão, Renata; Donato, Jose

    2014-11-01

    Several studies have shown that estrogens mimic leptin's effects on energy balance regulation. However, the findings regarding the consequences of reduced sex hormone levels on leptin sensitivity are divergent. In the present study, we employed different experimental paradigms to elucidate the interaction between estrogens, leptin, and energy balance regulation. We confirmed previous reports showing that ovariectomy caused a reduction in locomotor activity and energy expenditure leading mice to obesity and glucose intolerance. However, the acute and chronic anorexigenic effects of leptin were preserved in ovariectomized (OVX) mice despite their increased serum leptin levels. We studied hypothalamic gene expression at different time points after ovariectomy and observed that changes in the expression of genes involved in leptin resistance (suppressors of cytokine signaling and protein-tyrosine phosphatases) did not precede the early onset of obesity in OVX mice. On the contrary, reduced sex hormone levels caused an up-regulation of the long form of the leptin receptor (LepR), resulting in increased activation of leptin signaling pathways in OVX leptin-treated animals. The up-regulation of the LepR was observed in long-term OVX mice (30 d or 24 wk after ovariectomy) but not 7 days after the surgery. In addition, we observed a progressive decrease in the coexpression of LepR and estrogen receptor-α in the hypothalamus after the ovariectomy, resulting in a low percentage of dual-labeled cells in OVX mice. Taken together, our findings suggest that the weight gain caused by reduced sex hormone levels is not primarily caused by induction of a leptin-resistance state.

  16. In vitro activity of older and newer fluoroquinolones against efflux-mediated high-level ciprofloxacin-resistant Streptococcus pneumoniae.

    PubMed

    Daporta, Matilde Trigo; Muñoz Bellido, Juan Luis; Guirao, Genoveva Yagüe; Hernández, Manuel Segovia; García-Rodríguez, José Angel

    2004-08-01

    The effect of high-level efflux activity on the MICs of fluoroquinolones against Streptococcus pneumoniae in the absence of topoisomerase mutations leading to fluoroquinolones resistance was investigated. A S. pneumoniae ATCC 46619-derived strain with high-level efflux activity was obtained (SP-25A). Both the parent and obtained strains were tested against efflux substrates acriflavine (Acr) and ethidium bromide (EtBr), and against norfloxacin (NFX), ciprofloxacin (CFX), levofloxacin (LFX), moxifloxacin (MFX), trovafloxacin (TVX) and sitafloxacin (SFX), in presence and absence of the efflux pump inhibitor reserpine. gyrA, gyrB, parC and parE QRDR genes were amplified by PCR and sequenced. MICs of NFX and CFX against SP-25A were 64-fold higher than parent strain MICs (256 mg/L versus 4 mg/L and 64 mg/L versus 1mg/L, respectively). MIC of LFX increased from 1 to 4 mg/L and MICs of MFX, TVX and SFX remained virtually unchanged (0.1-0.2 mg/L). MICs of Acr and EtBr against SP-25A were 8- and 16-fold higher than against parent strains. In both cases, reserpine reverted MICs to the parent strain values (1 and 0.2 mg/L). Only parE showed two mutations leading to a Pro(454) --> Ser and Glu(443) changes, which have previously been shown not to lead to significant fluoroquinolones MIC increases. SP-25A showed a significant increase of MICs of the hydrophilic fluoroquinolones, apparently derived only from efflux activity. Efflux activity, at these high levels, can lead to high-level resistance to older hydrophilic fluoroquinolones, but does affect newer fluoroquinolones such as moxifloxacin, trovafloxacin and sitafloxacin.

  17. Efficacy of vancomycin and teicoplanin alone and in combination with streptomycin in experimental, low-level vancomycin-resistant, VanB-type Enterococcus faecalis endocarditis.

    PubMed Central

    Nicolau, D P; Marangos, M N; Nightingale, C H; Patel, K B; Cooper, B W; Quintiliani, R; Courvalin, P; Quintiliani, R

    1996-01-01

    The efficacy of vancomycin (VM) and teicoplanin (TE), alone and in combination with streptomycin (SM), against enterococci that express low-level VanB-type VM resistance was investigated in experimental endocarditis using isogenic strains of Enterococcus faecalis susceptible to glycopeptides and aminoglycosides or inducibly resistant to low levels of VM (MIC = 16 micrograms/ml). VM was significantly less active against the resistant strain than against the susceptible strain, establishing that low-level VanB-type VM resistance can influence therapeutic efficacy. By contrast, TE had equally good activity against both strains. VM or TE combined with SM was synergistic and bactericidal against the resistant strain in vitro. While both combinations were efficient in reducing bacterial density in vivo, TE plus SM was significantly superior to VM plus SM if valve sterilization was considered. These data suggest that despite the presence of low-level VanB-type resistance, combination therapy with a glycopeptide and SM (and presumably other aminoglycosides to which there is not high-level resistance) will nevertheless provide effective bactericidal activity. PMID:8787879

  18. Different Levels of Eccentric Resistance during Eight Weeks of Training Affect Muscle Strength and Lean Tissue Mass

    NASA Technical Reports Server (NTRS)

    English, K. L.; Loehr, J. A.; Lee, S. M. C.; Laughlin, M. S.; Hagan, R. D.

    2008-01-01

    Coupling concentric and eccentric muscle contractions appears to be important in the development of muscle strength and hypertrophy. The interim Resistive Exercise Device (iRED) currently used aboard the International Space Station does not seem to be as effective as free weight training in ambulatory subjects and has not completely protected against muscular deconditioning due to space flight. The lack of protection during space flight could be caused by iRED's proportionally lower eccentric resistance (60-70%) compared to concentric resistance. PURPOSE: To determine the effects of 8 wks of lower body resistive exercise training using five levels of eccentric resistance on muscle strength and lean tissue mass. METHODS: Forty untrained males (34.9 +/- 7 yrs, 80.9 +/- 9.8 kg, 178.2 +/- 7.1 cm; mean +/- SD) completed three 1-repetition maximum (1-RM) strength tests for both the supine leg press (LP) and supine heel raise (HR) prior to training; subjects were matched for LP strength and randomly assigned to one of five training groups. Concentric load (% 1-RM) was constant across groups during training, but each group trained with different levels of eccentric load (0%, 33%, 66%, 100%, or 138% of concentric). Subjects trained 3 d / wk for 8 wks using a periodized program for LP and HR based on percentages of the highest pre-training 1-RM. LP and HR 1-RM and leg lean mass (LLM; assessed by DEXA) were measured pre- and post-training. A two-way ANOVA was used to analyze all dependent measures. Tukey's post hoc tests were used to test significant main effects. Within group pre- to post-training changes were compared using paired t-tests with a Bonferroni adjustment. Statistical significance was set a priori at p 0.05. All data are expressed as mean +/- SE. RESULTS: LP 1-RM strength increased significantly in all groups pre- to post-training. The 138% group increase (20.1 +/- 3.7%) was significantly greater than the 0% (7.9 +/- 2.8%), 33% (7.7 +/- 4.6%), and 66% (7.5 +/- 4

  19. PLASMA SOLUBLE SGP130 LEVELS ARE INCREASED IN OLDER SUBJECTS WITH METABOLIC SYNDROME. THE ROLE OF INSULIN RESISTANCE

    PubMed Central

    Zuliani, Giovanni; Galvani, Matteo; Maggio, Marcello; Volpato, Stefano; Bandinelli, Stefania; Corsi, Anna Maria; Lauretani, Fulvio; Cherubini, Antonio; Guralnik, Jack M.; Fellin, Renato; Ferrucci, Luigi

    2010-01-01

    Objective Increased interleukin-6 plasma levels have been reported in metabolic syndrome (MS); nevertheless, it is unclear whether interleukin-6 activity is exerted through direct signalling only or also through the “trans-signalling”. This issue is important to clarify since signalling and “trans-signalling” affect different tissues. We investigated the relationship between MS and the interleukin-6 system in an older population. Methods Data from 997 older community dwelling individuals (age ≥ 65 years; females: 56.2%) enrolled the InChianti study were analyzed. Interleukin-6, soluble interleukin-6 receptor (sIL-6r), and soluble glycoprotein 130 (sgp130) were measured on plasma by ELISA. MS was defined by the NCEP-ATPIII criteria; 309 individuals (31%) resulted affected by MS. Results Subjects with MS had higher interleukin-6 and sgp130 levels compared to controls; a trend toward higher levels of sIL-6R was also observed. The risk of having MS was increased in individuals with high sIL-6r or/and sgp130 levels, independent of age, gender, and interleukin-6 levels. Elevated sgp130 levels were associated with higher plasma glucose, HOMA, triglycerides, and with diabetes both in subjects with and without MS. Although the risk of high sgp130 levels was generally associated with MS (O.R.:1.77, 95%C.I.: 1.39-2.25), this excess of risk was not present in MS phenotypes excluding the criteria “elevated glucose” or “elevated triglycerides”. Furthermore, the association between sgp130 and MS disappeared after adjustment for HOMA. Conclusions We found that older individuals with MS have increased sgp130 plasma levels compared with controls; nevertheless, our data suggest that this association might be mediated by insulin resistance. PMID:20869059

  20. Genetic linkage analysis of the lesser grain borer Rhyzopertha dominica identifies two loci that confer high-level resistance to the fumigant phosphine.

    PubMed Central

    Schlipalius, David I; Cheng, Qiang; Reilly, Paul E B; Collins, Patrick J; Ebert, Paul R

    2002-01-01

    High levels of inheritable resistance to phosphine in Rhyzopertha dominica have recently been detected in Australia and in an effort to isolate the genes responsible for resistance we have used random amplified DNA fingerprinting (RAF) to produce a genetic linkage map of R. dominica. The map consists of 94 dominant DNA markers with an average distance between markers of 4.6 cM and defines nine linkage groups with a total recombination distance of 390.1 cM. We have identified two loci that are responsible for high-level resistance. One provides approximately 50x resistance to phosphine while the other provides 12.5x resistance and in combination, the two genes act synergistically to provide a resistance level 250x greater than that of fully susceptible beetles. The haploid genome size has been determined to be 4.76 x 10(8) bp, resulting in an average physical distance of 1.2 Mbp per map unit. No recombination has been observed between either of the two resistance loci and their adjacent DNA markers in a population of 44 fully resistant F5 individuals, which indicates that the genes are likely to reside within 0.91 cM (1.1 Mbp) of the DNA markers. PMID:12072472

  1. Novel K540N mutation in Plasmodium falciparum dihydropteroate synthetase confers a lower level of sulfa drug resistance than does a K540E mutation.

    PubMed

    Lumb, Vanshika; Sharma, Yagya D

    2011-05-01

    Sulfadoxine (SDX) and sulfamethoxazole (SMX) each inhibit the Plasmodium falciparum dihydropteroate synthetase (PfDHPS), and certain point mutations in this enzyme yield the drug-resistant parasite. Using a simple Escherichia coli model system, we describe here the effect of the recently reported novel K540N mutation in PfDHPS on the level of SDX/SMX resistance. The survival rate of the transformed E. coli (DHPS-deficient strain) under different SDX or SMX concentrations revealed that the K540N mutation confers a lower level of drug resistance than its contemporary K540E mutation. Further, SMX was more effective than SDX in the E. coli system.

  2. Variability of cutaneous and nasal population levels between patients colonized and infected by multidrug-resistant bacteria in two Brazilian intensive care units

    PubMed Central

    Nicoli, Jacques R; Oliveira, Adriana

    2015-01-01

    Objective: To compare cutaneous and nasal population levels between patients colonized and infected by multidrug-resistant organisms in two intensive care units. Methods: A prospective cohort study was performed in adult intensive care units of two hospitals in Belo Horizonte, Brazil (April 2012 to February 2013). Clinical and demographic data were first collected by reviewing patients’ charts. Then, samples collected with nasal, groin, and perineum swabs were cultivated in selective media for 48 h at 37°C. After isolation, determination of antimicrobial susceptibility and biochemical identification were performed. Results: A total of 53 cases of colonization were observed by the following bacteria in decreasing frequencies: imipenem-resistant Acinetobacter baumannii (50.9%), vancomycin-resistant Enterococcus faecalis (43.4%), extended-spectrum beta-lactamase–producing Klebsiella pneumoniae (37.7%), imipenem-resistant Pseudomonas aeruginosa (32.1%), oxacillin-resistant Staphylococcus aureus (7.5%), and imipenem-resistant Klebsiella pneumoniae (5.7%). Among these colonization cases, 26 (49.0%) were followed by infection with bacteria phenotypically similar to those of the colonization. A relation between high population levels of colonization by most of the multidrug-resistant organisms at anatomical sites and a subsequent infection was observed. After colonization/infection, bacterial population levels decreased progressively and spontaneously until disappearance by day 45 in all the anatomical sites and for all the multidrug-resistant organisms. Conclusion: There was a correlation between high population levels of colonization by multidrug-resistant organisms at anatomical sites and a subsequent infection. Reduction in multidrug-resistant organism populations after colonization at anatomical sites could be a preventive measure to reduce evolution to infection as well as transmission of these bacteria between patients in intensive care unit. PMID:26770762

  3. Evolution of high-level ethambutol-resistant tuberculosis through interacting mutations in decaprenylphosphoryl-β-D-arabinose biosynthetic and utilization pathway genes.

    PubMed

    Safi, Hassan; Lingaraju, Subramanya; Amin, Anita; Kim, Soyeon; Jones, Marcus; Holmes, Michael; McNeil, Michael; Peterson, Scott N; Chatterjee, Delphi; Fleischmann, Robert; Alland, David

    2013-10-01

    To study the evolution of drug resistance, we genetically and biochemically characterized Mycobacterium tuberculosis strains selected in vitro for ethambutol resistance. Mutations in decaprenylphosphoryl-β-D-arabinose (DPA) biosynthetic and utilization pathway genes Rv3806c, Rv3792, embB and embC accumulated to produce a wide range of ethambutol minimal inhibitory concentrations (MICs) that depended on mutation type and number. Rv3806c mutations increased DPA synthesis, causing MICs to double from 2 to 4 μg/ml in a wild-type background and to increase from 16 to 32 μg/ml in an embB codon 306 mutant background. Synonymous mutations in Rv3792 increased the expression of downstream embC, an ethambutol target, resulting in MICs of 8 μg/ml. Multistep selection was required for high-level resistance. Mutations in embC or very high embC expression were observed at the highest resistance level. In clinical isolates, Rv3806c mutations were associated with high-level resistance and had multiplicative effects with embB mutations on MICs. Ethambutol resistance is acquired through the acquisition of mutations that interact in complex ways to produce a range of MICs, from those falling below breakpoint values to ones representing high-level resistance.

  4. Inverse Relationship of the CMKLR1 Relative Expression and Chemerin Serum Levels in Obesity with Dysmetabolic Phenotype and Insulin Resistance

    PubMed Central

    Corona-Meraz, Fernanda-Isadora; Navarro-Hernández, Rosa-Elena; Ruíz-Quezada, Sandra-Luz; Madrigal-Ruíz, Perla-Monserrat; Castro-Albarrán, Jorge; Chavarría-Ávila, Efraín; Guzmán-Ornelas, Milton-Omar; Gómez-Bañuelos, Eduardo; Petri, Marcelo-Herón; Ramírez-Cedano, Joel-Isidro; Aguilar-Aldrete, María-Elena; Ríos-Ibarra, Clara; Vázquez-Del Mercado, Mónica

    2016-01-01

    Background. In obesity there is a subclinical chronic low-grade inflammatory response where insulin resistance (IR) may develop. Chemerin is secreted in white adipose tissue and promotes low-grade inflammatory process, where it expressed CMKLR1 receptor. The role of chemerin and CMKLR1 in inflammatory process secondary to obesity is not defined yet. Methods. Cross-sectional study with 134 individuals classified as with and without obesity by body mass index (BMI) and IR. Body fat storage measurements and metabolic and inflammatory markers were measured by routine methods. Soluble chemerin and basal levels of insulin by ELISA and relative expression of CMKLR1 were evaluated with qPCR and 2−ΔΔCT method. Results. Differences (P < 0.05) were observed between obesity and lean individuals in body fat storage measurements and metabolic-inflammatory markers. Both CMKLR1 expression and chemerin levels were increased in obesity without IR. Soluble chemerin levels correlate with adiposity and metabolic markers (r = 8.8% to 38.5%), P < 0.05. Conclusion. The increment of CMKLR1 expression was associated with insulin production. Increased serum levels of chemerin in obesity were observed, favoring a dysmetabolic response. The results observed in this study suggest that both chemerin and CMKLR1 have opposite expression in the context of low-grade inflammatory response manifested in the development of IR. PMID:27239101

  5. Combined expression of multidrug resistance protein (MRP) and glutathione S-transferase P1-1 (GSTP1-1) in MCF7 cells and high level resistance to the cytotoxicities of ethacrynic acid but not oxazaphosphorines or cisplatin.

    PubMed

    Morrow, C S; Smitherman, P K; Townsend, A J

    1998-10-15

    We tested the hypothesis that combined increased expression of human glutathione S-transferase P1-1 (GSTP1-1), an enzyme that catalyzes the conjugation with glutathione of several toxic electrophiles, and the glutathione-conjugate efflux pump, multidrug resistance protein (MRP), confers high level resistance to the cytotoxicities of anticancer and other drugs. To accomplish this, we developed MCF7 breast carcinoma cell derivatives that express high levels of GSTP1-1 and MRP, alone and in combination. Parental MCF7 cells, which express no GSTP1-1 and negligible MRP, served as control cells. We found that either MRP or GSTP1-1 alone conferred significant resistance to ethacrynic acid cytotoxicity. Moreover, combined expression of GSTP1-1 and MRP conferred a high level of resistance to ethacrynic acid that was greater than resistance conferred by either protein alone. Increased MRP was also associated with modest resistance to the oxazaphosphorine compounds mafosfamide, 4-hydroxycyclophosphamide, and 4-hydroperoxycyclophosphamide. However, coordinated expression of GSTP1-1 with MRP failed to augment this modest resistance. Similarly, GSTP1-1 had no effect on the sensitivities to cisplatin of MCF7 cells regardless of MRP expression. These results establish that coordinated expression of MRP and GSTP1-1 can confer high level resistance to the cytotoxicities of some drugs, including ethacrynic acid, but that such resistance is variable and does not apply to all toxic drugs that can potentially form glutathione conjugates in either spontaneous or GSTP1-1-catalyzed reactions.

  6. 25-Hydroxyvitamin D3 Levels, BsmI Polymorphism and Insulin Resistance in Brazilian Amazonian Children

    PubMed Central

    Cobayashi, Fernanda; Hatzlhoffer Lourenço, Bárbara; Augusto Cardoso, Marly

    2015-01-01

    Vitamin D is associated with a wide range of other functions beyond bone development. We evaluated the factors associated with 25-hydroxyvitamin D levels in 974 children aged ≤10 years and the impact of BsmI polymorphism of the vitamin D receptor (VDR) gene (rs1544410) on metabolic parameters in a subsample (n: 430) with a follow-up 2 years later from the initial population-based cross-sectional study. Multiple linear regression models were used in the analyses. The prevalence (95% CI) of vitamin D deficiency, insufficiency and sufficiency of children was 11.1% (9.2–13.2), 21.8% (19.2–24.5) and 67.2% (64.1–70.1), respectively. Overall, 23% of the variation in serum 25-hydroxyvitamin D concentrations was accounted for by BsmI polymorphism β = −0.053 (95% CI) (−0.100, −0.006), maternal schooling (≥9 years) β = 0.100 (0.039, 0.161), serum vitamin E β = 0.478 (0.381, 0.574), total cholesterol concentration β = 0.232 (0.072, 0.393) and serum folate β = 0.064 (0.013, 0.115). BsmI polymorphism was positively associated with HOMA-IR β = 0.122 (0.002, 0.243) and fasting glucose concentration β = 1.696 (0.259, 3.133). In conclusion, variables related to socioeconomic level, the presence of the allele risk for BsmI and other nutrient concentrations were associated with serum 25-hydroxyvitamin D concentrations. Our results suggest that BsmI polymorphism is correlated with metabolic outcomes. PMID:26047339

  7. Optimal dietary protein level improved growth, disease resistance, intestinal immune and physical barrier function of young grass carp (Ctenopharyngodon idella).

    PubMed

    Xu, Jing; Wu, Pei; Jiang, Wei-Dan; Liu, Yang; Jiang, Jun; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu; Feng, Lin

    2016-08-01

    This study investigated the effects of dietary proteins on the growth, disease resistance, intestinal immune and physical barrier functions of young grass carp (Ctenopharyngodon idella). A total of 540 young grass carp (264.11 ± 0.76 g) were fed six diets containing graded levels of protein (143.1, 176.7, 217.2, 257.5, 292.2 and 322.8 g digestible protein kg(-1) diet) for 8 weeks. After the growth trial, fish were challenged with Aeromonas hydrophila and mortalities were recorded for 14 days. The results indicated that optimal dietary protein levels: increased the production of antibacterial components, up-regulated anti-inflammatory cytokines, inhibitor of κBα, target of rapamycin and ribosomal protein S6 kinases 1 mRNA levels, whereas down-regulated pro-inflammatory cytokines, nuclear factor kappa B (NF-κB) P65, NF-κB P52, c-Rel, IκB kinase β, IκB kinase γ and eIF4E-binding proteins 2 mRNA levels in three intestinal segments of young grass carp (P < 0.05), suggesting that optimal dietary protein level could enhance fish intestinal immune barrier function; up-regulated the mRNA levels of tight junction complexes, B-cell lymphoma protein-2, inhibitor of apoptosis proteins, myeloid cell leukemia-1 and NF-E2-related factor 2, and increased the activities and mRNA levels of antioxidant enzymes, whereas down-regulated myosin light chain kinase, cysteinyl aspartic acid-protease 2, 3, 7, 8, 9, fatty acid synthetase ligand, apoptotic protease activating factor-1, Bcl-2 associated X protein, p38 mitogen-activated protein kinase, c-Jun N-terminal protein kinase and Kelch-like-ECH-associated protein 1b mRNA levels, and decreased reactive oxygen species, malondialdehyde and protein carbonyl contents in three intestinal segments of young grass carp (P < 0.05), indicating that optimal dietary protein level could improve fish intestinal physical barrier function. Finally, the optimal dietary protein levels for the growth performance (PWG) and against enteritis

  8. Blood Mercury Levels of Zebra Finches Are Heritable: Implications for the Evolution of Mercury Resistance

    PubMed Central

    Buck, Kenton A.; Varian-Ramos, Claire W.; Cristol, Daniel A.; Swaddle, John P.

    2016-01-01

    Mercury is a ubiquitous metal contaminant that negatively impacts reproduction of wildlife and has many other sub-lethal effects. Songbirds are sensitive bioindicators of mercury toxicity and may suffer population declines as a result of mercury pollution. Current predictions of mercury accumulation and biomagnification often overlook possible genetic variation in mercury uptake and elimination within species and the potential for evolution in affected populations. We conducted a study of dietary mercury exposure in a model songbird species, maintaining a breeding population of zebra finches (Taeniopygia guttata) on standardized diets ranging from 0.0–2.4 μg/g methylmercury. We applied a quantitative genetics approach to examine patterns of variation and heritability of mercury accumulation within dietary treatments using a method of mixed effects modeling known as the 'animal model'. Significant variation in blood mercury accumulation existed within each treatment for birds exposed at the same dietary level; moreover, this variation was highly repeatable for individuals. We observed substantial genetic variation in blood mercury accumulation for birds exposed at intermediate dietary concentrations. Taken together, this is evidence that genetic variation for factors affecting blood mercury accumulation could be acted on by selection. If similar heritability for mercury accumulation exists in wild populations, selection could result in genetic differentiation for populations in contaminated locations, with possible consequences for mercury biomagnification in food webs. PMID:27668745

  9. Blood Mercury Levels of Zebra Finches Are Heritable: Implications for the Evolution of Mercury Resistance.

    PubMed

    Buck, Kenton A; Varian-Ramos, Claire W; Cristol, Daniel A; Swaddle, John P

    Mercury is a ubiquitous metal contaminant that negatively impacts reproduction of wildlife and has many other sub-lethal effects. Songbirds are sensitive bioindicators of mercury toxicity and may suffer population declines as a result of mercury pollution. Current predictions of mercury accumulation and biomagnification often overlook possible genetic variation in mercury uptake and elimination within species and the potential for evolution in affected populations. We conducted a study of dietary mercury exposure in a model songbird species, maintaining a breeding population of zebra finches (Taeniopygia guttata) on standardized diets ranging from 0.0-2.4 μg/g methylmercury. We applied a quantitative genetics approach to examine patterns of variation and heritability of mercury accumulation within dietary treatments using a method of mixed effects modeling known as the 'animal model'. Significant variation in blood mercury accumulation existed within each treatment for birds exposed at the same dietary level; moreover, this variation was highly repeatable for individuals. We observed substantial genetic variation in blood mercury accumulation for birds exposed at intermediate dietary concentrations. Taken together, this is evidence that genetic variation for factors affecting blood mercury accumulation could be acted on by selection. If similar heritability for mercury accumulation exists in wild populations, selection could result in genetic differentiation for populations in contaminated locations, with possible consequences for mercury biomagnification in food webs.

  10. Association of mutation patterns in GyrA and ParC genes with quinolone resistance levels in lactic acid bacteria.

    PubMed

    Li, Shaoying; Li, Zhen; Wei, Wan; Ma, Chunyan; Song, Xiaomin; Li, Shufen; He, Wenying; Tian, Jianjun; Huo, Xiaoyan

    2015-02-01

    The quinolone resistance of 19 lactic acid bacterial strains belonging to the genera Enterococcus and Lactobacillus isolated from the natural fermented koumiss and yoghurt were investigated. The objective of this study was to determine the quinolone resistance levels and to explore the association of the resistance with the mutation patterns in gyrA and parC genes, as is currently recommended by the Food and Agriculture Organization/World Health Organization Joint Expert Committee in Guidelines for Evaluation of Probiotics in Food for probiotic lactic acid bacteria drug resistance in 2001. The Oxford Cup method and double-tube dilution method were used to determine the quinolone resistance levels of the isolated strains. Generally, all of the 19 strains showed resistance towards norfloxacin and ciprofloxacin when the Oxford cup method was used, whereas the incidence was lower (to norfloxacin 89.5% and to ciprofloxacin 68.4%) when minimum inhibitory concentration breakpoints (CLSI M100-S23) were tested. Furthermore, gene sequencing was conducted on gyrA and parC of topoisomerase II of these isolated strains. The genetic basis for quinolone resistance may be closely related to mutations in gyrA genes as there were 10 mutation sites in amino-acid sequences encoded by gyrA genes in 10 quinolone resistance strains and 14 mutation sites in Enterococcus durans HZ28, whereas no typical mutations were detected in parC genes.

  11. Leveling

    USGS Publications Warehouse

    1966-01-01

    Geodetic leveling by the U.S. Geological Survey provides a framework of accurate elevations for topographic mapping. Elevations are referred to the Sea Level Datum of 1929. Lines of leveling may be run either with automatic or with precise spirit levels, by either the center-wire or the three-wire method. For future use, the surveys are monumented with bench marks, using standard metal tablets or other marking devices. The elevations are adjusted by least squares or other suitable method and are published in lists of control.

  12. Evolution of a Double Amino Acid Substitution in the 5-Enolpyruvylshikimate-3-Phosphate Synthase in Eleusine indica Conferring High-Level Glyphosate Resistance1

    PubMed Central

    Yu, Qin; Jalaludin, Adam; Han, Heping; Chen, Ming; Sammons, R. Douglas; Powles, Stephen B.

    2015-01-01

    Glyphosate is the most important and widely used herbicide in world agriculture. Intensive glyphosate selection has resulted in the widespread evolution of glyphosate-resistant weed populations, threatening the sustainability of this valuable once-in-a-century agrochemical. Field-evolved glyphosate resistance due to known resistance mechanisms is generally low to modest. Here, working with a highly glyphosate-resistant Eleusine indica population, we identified a double amino acid substitution (T102I + P106S [TIPS]) in the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene in glyphosate-resistant individuals. This TIPS mutation recreates the biotechnology-engineered commercial first generation glyphosate-tolerant EPSPS in corn (Zea mays) and now in other crops. In E. indica, the naturally evolved TIPS mutants are highly (more than 180-fold) resistant to glyphosate compared with the wild type and more resistant (more than 32-fold) than the previously known P106S mutants. The E. indica TIPS EPSPS showed very high-level (2,647-fold) in vitro resistance to glyphosate relative to the wild type and is more resistant (600-fold) than the P106S variant. The evolution of the TIPS mutation in crop fields under glyphosate selection is likely a sequential event, with the P106S mutation being selected first and fixed, followed by the T102I mutation to create the highly resistant TIPS EPSPS. The sequential evolution of the TIPS mutation endowing high-level glyphosate resistance is an important mechanism by which plants adapt to intense herbicide selection and a dramatic example of evolution in action. PMID:25717039

  13. GidB mutation as a phylogenetic marker for Q1 cluster Mycobacterium tuberculosis isolates and intermediate-level streptomycin resistance determinant in Lisbon, Portugal.

    PubMed

    Perdigão, J; Macedo, R; Machado, D; Silva, C; Jordão, L; Couto, I; Viveiros, M; Portugal, I

    2014-05-01

    Development of streptomycin resistance in Mycobacterium tuberculosis is usually associated with mutations in rpsL and rrs genes, although up to 50% of clinical streptomycin-resistant isolates may present no mutation in either of these genes. In the present report we investigate the role of gidB gene mutations in streptomycin resistance. We have analyzed 52 streptomycin-resistant and 30 streptomycin-susceptible Mycobacterium tuberculosis clinical isolates by sequencing and endonuclease analysis of the gidB and rpsL genes. All clinical isolates were genotyped by 12-loci MIRU-VNTR. The gidB gene of 18 streptomycin-resistant isolates was sequenced and four missense mutations were found: F12L (1/18), L16R (18/18), A80P (4/18) and S100F (18/18). The remaining isolates were screened by endonuclease analysis for mutations A80P in the gidB gene and K43R in the rpsL gene. Overall, mutation A80P in the gidB gene was found in eight streptomycin-resistant isolates and 11 streptomycin-susceptible multidrug-resistant isolates. Also noteworthy, is the fact that gidB mutations were only present in isolates without rpsL and rrs mutations, all from genetic cluster Q1. Streptomycin quantitative drug susceptibility testing showed that isolates carrying the gidB A80P mutation were streptomycin intermediate-level resistant and that standard drug susceptibility testing yielded inconsistent results, probably due to borderline resistance. We conclude that gidB mutations may explain the high number of streptomycin-resistant strains with no mutation in rpsL or rrs. These mutations might occasionally confer low-level streptomycin resistance that will go undetected in standard susceptibility testing.

  14. Evolution of a double amino acid substitution in the 5-enolpyruvylshikimate-3-phosphate synthase in Eleusine indica conferring high-level glyphosate resistance.

    PubMed

    Yu, Qin; Jalaludin, Adam; Han, Heping; Chen, Ming; Sammons, R Douglas; Powles, Stephen B

    2015-04-01

    Glyphosate is the most important and widely used herbicide in world agriculture. Intensive glyphosate selection has resulted in the widespread evolution of glyphosate-resistant weed populations, threatening the sustainability of this valuable once-in-a-century agrochemical. Field-evolved glyphosate resistance due to known resistance mechanisms is generally low to modest. Here, working with a highly glyphosate-resistant Eleusine indica population, we identified a double amino acid substitution (T102I+P106S [TIPS]) in the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene in glyphosate-resistant individuals. This TIPS mutation recreates the biotechnology-engineered commercial first generation glyphosate-tolerant EPSPS in corn (Zea mays) and now in other crops. In E. indica, the naturally evolved TIPS mutants are highly (more than 180-fold) resistant to glyphosate compared with the wild type and more resistant (more than 32-fold) than the previously known P106S mutants. The E. indica TIPS EPSPS showed very high-level (2,647-fold) in vitro resistance to glyphosate relative to the wild type and is more resistant (600-fold) than the P106S variant. The evolution of the TIPS mutation in crop fields under glyphosate selection is likely a sequential event, with the P106S mutation being selected first and fixed, followed by the T102I mutation to create the highly resistant TIPS EPSPS. The sequential evolution of the TIPS mutation endowing high-level glyphosate resistance is an important mechanism by which plants adapt to intense herbicide selection and a dramatic example of evolution in action.

  15. Detection of the esp gene in high-level gentamicin resistant Enterococcus faecalis strains from pet animals in Japan.

    PubMed

    Harada, Tetsuya; Tsuji, Noboru; Otsuki, Koichi; Murase, Toshiyuki

    2005-03-20

    We investigated the prevalence of the esp gene and the susceptibility to gentamicin in Enterococcus faecalis and E. faecium strains obtained from pet animals. Nine of 30 E. faecalis and 2 of 38 E. faecium strains from the pet animals had the esp gene. Three esp-positive E. faecalis strains, which were isolated from two dogs and a cat, showed gentamicin MICs of > or =256 microg/ml and harbored the high-level gentamicin resistance (HLGR) gene, aac(6')-Ie-aph(2'')-Ia. Of the nine esp-positive E. faecalis strains, five, including the three strains with the HLGR gene, were closely related by numerical analysis of PFGE patterns. Longitudinal investigation needs to elucidate whether the HLGR gene was incorporated into a subpopulation of the esp-positive E. faecalis.

  16. Evaluation of the range shifter model for proton pencil-beam scanning for the Eclipse v.11 treatment planning system.

    PubMed

    Matysiak, Witold; Yeung, Daniel; Slopsema, Roelf; Li, Zuofeng

    2016-03-08

    Existing proton therapy pencil-beam scanning (PBS) systems have limitations on the minimum range to which a patient can be treated. This limitation arises from practical considerations, such as beam current intensity, layer spacing, and delivery time. The range shifter (RS) - a slab of stopping material inserted between the nozzle and the patient - is used to reduce the residual range of the incident beam so that the treatment ranges can be extended to shallow depths. Accurate modeling of the RS allows one to calculate the beam spot size entering the patient, given the proton energy, for arbitrary positions and thicknesses of the RS in the beam path. The Eclipse version 11 (v11) treatment planning system (TPS) models RS-induced beam widening by incorporating the scattering properties of the RS material into the V-parameter. Monte Carlo simulations with Geant4 code and analytical calculations using the Fermi-Eyges (FE) theory with Highland approximation of multiple Coulomb scattering (MCS) were employed to calculate proton beam widening due to scattering in the RS. We demonstrated that both methods achieved consistent results and could be used as a benchmark for evaluating the Eclipse V-parameter model. In most cases, the V-parameter model correctly predicted the beam spot size after traversing the RS. However, Eclipse did not enforce the constraint for a nonnegative covariance matrix when fitting the spot sizes to derive the phase space parameters, which resulted in incorrect calculations under specific conditions. In addition, Eclipse v11 incorrectly imposed limits on the individual values of the phase space parameters, which could lead to incorrect spot size values in the air calculated for beams with spot sigmas <3.8 mm. Notably, the TPS supplier (Varian) and hardware vendor (Ion Beam Applications) inconsistently refer to the RS position, which may result in improper spot size calculations.

  17. Evaluation of the range shifter model for proton pencil-beam scanning for the Eclipse v.11 treatment planning system.

    PubMed

    Matysiak, Witold; Yeung, Daniel; Slopsema, Roelf; Li, Zuofeng

    2016-03-01

    Existing proton therapy pencil-beam scanning (PBS) systems have limitations on the minimum range to which a patient can be treated. This limitation arises from practical considerations, such as beam current intensity, layer spacing, and delivery time. The range shifter (RS) - a slab of stopping material inserted between the nozzle and the patient - is used to reduce the residual range of the incident beam so that the treatment ranges can be extended to shallow depths. Accurate modeling of the RS allows one to calculate the beam spot size entering the patient, given the proton energy, for arbitrary positions and thicknesses of the RS in the beam path. The Eclipse version 11 (v11) treatment planning system (TPS) models RS-induced beam widening by incorporating the scattering properties of the RS material into the V-parameter. Monte Carlo simulations with Geant4 code and analytical calculations using the Fermi-Eyges (FE) theory with Highland approximation of multiple Coulomb scattering (MCS) were employed to calculate proton beam widening due to scattering in the RS. We demonstrated that both methods achieved consistent results and could be used as a benchmark for evaluating the Eclipse V-parameter model. In most cases, the V-parameter model correctly predicted the beam spot size after traversing the RS. However, Eclipse did not enforce the constraint for a nonnegative covariance matrix when fitting the spot sizes to derive the phase space parameters, which resulted in incorrect calculations under specific conditions. In addition, Eclipse v11 incorrectly imposed limits on the individual values of the phase space parameters, which could lead to incorrect spot size values in the air calculated for beams with spot sigmas <3.8 mm. Notably, the TPS supplier (Varian) and hardware vendor (Ion Beam Applications) inconsistently refer to the RS position, which may result in improper spot size calculations. PACS number(s): 87.53.Jw, 87.53.Kn, 87.55.kd, 87.56.-v.

  18. Mycobacterium tuberculosis rrs A1401G mutation correlates with high-level resistance to kanamycin, amikacin, and capreomycin in clinical isolates from mainland China.

    PubMed

    Du, Qinglin; Dai, Guangming; Long, Quanxin; Yu, Xia; Dong, Lingling; Huang, Hairong; Xie, Jianping

    2013-10-01

    Mutations correlating phenotypic resistance level with the injectable second-line anti-tuberculosis drugs (SLDs) including kanamycin (KAN), amikacin (AMK), and capreomycin (CAP) remain elusive. A collection of 114 Mycobacterium tuberculosis clinical isolates from mainland China was analyzed. The minimum inhibitory concentration (MIC) of each strain was determined and the sequences of rrs, tlyA, promoter of eis as well as 5' untranslated region (UTR) of whiB7 were amplified and sequenced. No mutation in tlyA, promoter of eis and 5' UTR of whiB7, was found to be associated with resistance among these samples. Sequencing data of 1400 rrs region demonstrated the A1401G mutation in rrs was prevalent, which presented in 84% of the KAN resistant isolates while only in about 50% of the AMK or CAP resistant isolates. Furthermore, most of the resistant isolates with A1401G mutation showed high-level resistance to these injectable SLDs. In conclusion, our results suggest the rrs A1401G mutation was related to high-level resistance to KAN, AMK, and CAP in M. tuberculosis isolates from mainland China.

  19. New Rice for Africa (NERICA) cultivars exhibit different levels of post-attachment resistance against the parasitic weeds Striga hermonthica and Striga asiatica.

    PubMed

    Cissoko, Mamadou; Boisnard, Arnaud; Rodenburg, Jonne; Press, Malcolm C; Scholes, Julie D

    2011-12-01

    Striga hermonthica and S. asiatica are root parasitic weeds that infect the major cereal crops of sub-Saharan Africa causing severe losses in yield. The interspecific upland NEw RICe for Africa (NERICA) cultivars are popular amongst subsistence farmers, but little is known about their post-attachment resistance against Striga. Here, we evaluate the post-attachment resistance levels of the NERICA cultivars and their parents against ecotypes of S. hermonthica and S.asiatica, characterize the phenotype of the resistance mechanisms and determine the effect of Striga on host biomass. Some NERICA cultivars showed good broad-spectrum resistance against several Striga ecotypes, whereas others showed intermediate resistance or were very susceptible. The phenotype of a resistant interaction was often characterized by an inability of the parasite to penetrate the endodermis. Moreover, some parasites formed only a few connections to the host xylem, grew slowly and remained small. The most resistant NERICA cultivars were least damaged by Striga, although even a small number of parasites caused a reduction in above-ground host biomass. The elucidation of the molecular genetic basis of the resistance mechanisms and tolerance would allow the development of cultivars with multiple, durable resistance for use in farmers' fields.

  20. No Effect of Added Sugar Consumed at Median American Intake Level on Glucose Tolerance or Insulin Resistance

    PubMed Central

    Lowndes, Joshua; Sinnett, Stephanie S.; Rippe, James M.

    2015-01-01

    Excess sugar consumption may promote adverse changes in hepatic and total body insulin resistance. Debate continues over the effects of sugars at more typically consumed levels and whether the identity of the sugar consumed is important. In the present study participants (20–60 years old) were randomly assigned to one of five groups, three that consumed low fat milk with added fructose containing sugars in amounts equivalent to the 50th percentile of fructose consumption (US), one which consumed low-fat milk sweetened with glucose, and one unsweetened low-fat milk control group. The intervention lasted ten weeks. In the entire study population there was less than 1 kg increase in weight (73.6 ± 13.0 vs. 74.5 ± 13.3 kg, p < 0.001), but the change in weight was comparable among groups (p > 0.05). There were no changes in fasting glucose (49 ± 0.4 vs. 5.0 ± 0.5 mmol/L), insulin (56.9 ± 38.9 vs. 61.8 ± 50.0 pmol/L), or insulin resistance, as measured by the Homeostasis Model Assessment method (1.8 ± 1.3 vs. 2.0 ± 1.5, all p > 0.05). These data suggest that added sugar consumed at the median American intake level does not produce changes in measures of insulin sensitivity or glucose tolerance and that no sugar has more deleterious effects than others. PMID:26512691

  1. Transcriptional immune response in mesenteric lymph nodes in pigs with different levels of resistance to Ascaris suum.

    PubMed

    Skallerup, Per; Nejsum, Peter; Cirera, Susanna; Skovgaard, Kerstin; Pipper, Christian B; Fredholm, Merete; Jørgensen, Claus B; Thamsborg, Stig M

    2017-03-01

    A single nucleotide polymorphism on chromosome 4 (SNP TXNIP) has been reported to be associated with roundworm (Ascaris suum) burden in pigs. The objective of the present study was to analyse the immune response to A. suum mounted by pigs with genotype AA (n = 24) and AB (n = 23) at the TXNIP locus. The pigs were repeatedly infected with A. suum from eight weeks of age until necropsy eight weeks later. An uninfected control group (AA; n = 5 and AB; n = 5) was also included. At post mortem, we collected mesenteric lymph nodes and measured the expression of 28 selected immune-related genes. Recordings of worm burdens confirmed our previous results that pigs of the AA genotype were more resistant to infection than AB pigs. We estimated the genotype difference in relative expression levels in infected and uninfected animals. No significant change in expression levels between the two genotypes due to infection was observed for any of the genes, although IL-13 approached significance (P = 0.08; Punadjusted = 0.003). Furthermore, statistical analysis testing for the effect of infection separately in each genotype showed significant up-regulation of IL-13 (P<0.05) and CCL17 (P<0.05) following A. suum infection in the 'resistant' AA genotype and not in the 'susceptible' AB genotype. Pigs of genotype AB had higher expression of the high-affinity IgG receptor (FCGR1A) than AA pigs in both infected and non-infected animals (P = 1.85*10-11).

  2. High-Level Heat Resistance of Spores of Bacillus amyloliquefaciens and Bacillus licheniformis Results from the Presence of a spoVA Operon in a Tn1546 Transposon.

    PubMed

    Berendsen, Erwin M; Koning, Rosella A; Boekhorst, Jos; de Jong, Anne; Kuipers, Oscar P; Wells-Bennik, Marjon H J

    2016-01-01

    Bacterial endospore formers can produce spores that are resistant to many food processing conditions, including heat. Some spores may survive heating processes aimed at production of commercially sterile foods. Recently, it was shown that a spoVA operon, designated spoVA(2mob), present on a Tn1546 transposon in Bacillus subtilis, leads to profoundly increased wet heat resistance of B. subtilis spores. Such Tn1546 transposon elements including the spoVA(2mob) operon were also found in several strains of Bacillus amyloliquefaciens and Bacillus licheniformis, and these strains were shown to produce spores with significantly higher resistances to wet heat than their counterparts lacking this transposon. In this study, the locations and compositions of Tn1546 transposons encompassing the spoVA(2mob) operons in B. amyloliquefaciens and B. licheniformis were analyzed. Introduction of these spoVA(2mob) operons into B. subtilis 168 (producing spores that are not highly heat resistant) rendered mutant 168 strains that produced high-level heat resistant spores, demonstrating that these elements in B. amyloliquefaciens and B. licheniformis are responsible for high level heat resistance of spores. Assessment of growth of the nine strains of each species between 5.2°C and 57.7°C showed some differences between strains, especially at lower temperatures, but all strains were able to grow at 57.7°C. Strains of B. amyloliquefaciens and B. licheniformis that contain the Tn1546 elements (and produce high-level heat resistant spores) grew at temperatures similar to those of their Tn1546-negative counterparts that produce low-level heat resistant spores. The findings presented in this study allow for detection of B. amyloliquefaciens and B. licheniformis strains that produce highly heat resistant spores in the food chain.

  3. High-Level Heat Resistance of Spores of Bacillus amyloliquefaciens and Bacillus licheniformis Results from the Presence of a spoVA Operon in a Tn1546 Transposon

    PubMed Central

    Berendsen, Erwin M.; Koning, Rosella A.; Boekhorst, Jos; de Jong, Anne; Kuipers, Oscar P.; Wells-Bennik, Marjon H. J.

    2016-01-01

    Bacterial endospore formers can produce spores that are resistant to many food processing conditions, including heat. Some spores may survive heating processes aimed at production of commercially sterile foods. Recently, it was shown that a spoVA operon, designated spoVA2mob, present on a Tn1546 transposon in Bacillus subtilis, leads to profoundly increased wet heat resistance of B. subtilis spores. Such Tn1546 transposon elements including the spoVA2mob operon were also found in several strains of Bacillus amyloliquefaciens and Bacillus licheniformis, and these strains were shown to produce spores with significantly higher resistances to wet heat than their counterparts lacking this transposon. In this study, the locations and compositions of Tn1546 transposons encompassing the spoVA2mob operons in B. amyloliquefaciens and B. licheniformis were analyzed. Introduction of these spoVA2mob operons into B. subtilis 168 (producing spores that are not highly heat resistant) rendered mutant 168 strains that produced high-level heat resistant spores, demonstrating that these elements in B. amyloliquefaciens and B. licheniformis are responsible for high level heat resistance of spores. Assessment of growth of the nine strains of each species between 5.2°C and 57.7°C showed some differences between strains, especially at lower temperatures, but all strains were able to grow at 57.7°C. Strains of B. amyloliquefaciens and B. licheniformis that contain the Tn1546 elements (and produce high-level heat resistant spores) grew at temperatures similar to those of their Tn1546-negative counterparts that produce low-level heat resistant spores. The findings presented in this study allow for detection of B. amyloliquefaciens and B. licheniformis strains that produce highly heat resistant spores in the food chain. PMID:27994575

  4. Mangrove expansion in the Gulf of Mexico with climate change: Implications for wetland health and resistance to rising sea levels

    NASA Astrophysics Data System (ADS)

    Comeaux, Rebecca S.; Allison, Mead A.; Bianchi, Thomas S.

    2012-01-01

    Black mangroves ( Avicennia spp.) are hypothesized to expand their latitudinal range with global climate change in the 21st century, induced by a reduction in the frequency and severity of coastal freezes, which are known to limit mangrove colony extent and individual tree size. The Gulf of Mexico is a prime candidate for population expansion to occur because it is located at the northward limit of black mangrove habitat. This may come at the expense of existing coastal saline wetlands that are dominantly Spartina spp. marsh grasses. The present study was conducted to focus on the implications of a marsh to mangrove transition in Gulf wetlands, specifically: (1) wetland resistance to accelerating eustatic sea level rise (ESLR) rates; (2) resistance to wave attack in large storms (increased cyclonic storm frequency/intensity is predicted with future climate warming); and (3) organic carbon sequestration and wetland soil geochemistry. Field sites of adjacent and inter-grown Avicennia germinans mangrove and Spartina marsh populations in similar geomorphological setting were selected in back-barrier areas near Port Aransas and Galveston, TX. Elevation surveys in the more mature Port Aransas site indicate mangrove vegetated areas are 4 cm higher in elevation than surrounding marsh on an average regional scale, and 1-2 cm higher at the individual mangrove scale. 210Pb and 137Cs accumulation rates and loss on ignition data indicate that mineral trapping is 4.1 times higher and sediment organics are 1.7 times lower in mangroves at Port Aransas. This additional mineral trapping does not differ in grain size character from marsh accumulation. Elevation change may also be effected by soil displacement of higher root volumes in mangrove cores. Port Aransas porosities are lower in mangrove rooted horizons, with a corresponding increase in sediment strength, suggesting mangrove intervals are more resistant to wave-induced erosion during storm events. Port Aransas mangroves

  5. Role of free testosterone levels in patients with metastatic castration-resistant prostate cancer receiving second-line therapy

    PubMed Central

    von Klot, Christoph A.; Kuczyk, Markus A.; Boeker, Alena; Reuter, Christoph; Imkamp, Florian; Herrmann, Thomas R.W.; Tezval, Hossein; Kramer, Mario W.; Perner, Sven; Merseburger, Axel S.

    2017-01-01

    A range of new treatment options has recently become available for patients with advanced metastatic castration-resistant prostate cancer (mCRPC). Androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone is continued when performing chemotherapy or androgen deprivation with new second-generation therapeutic agents such as enzalutamide or abiraterone acetate. Despite the fact that free testosterone (FT) is the biologically active form, it is common practice that androgen suppression is monitored via total testosterone levels only. The aim of the present study was to evaluate the role of FT as a prognostic biomarker for cancer-specific survival (CSS) and its feasibility as an ADT monitoring biomarker in patients with mCRPC for the first time. The requirement for continued ADT in mCRPC patients is discussed within the basis of the current literature. A total of 34 patients with continuous measurements of FT levels and mCRPC status underwent therapy with docetaxel, abiraterone acetate, enzalutamide, cabozantinib, carboplatin or cabazitaxel. Data were obtained from the Departments of Urology and Urological Oncology, Hannover Medical School (Hannover, Germany) between March 2009 and April 2014. A cutoff point of 0.5 pg/ml was used to discriminate between patients according to FT levels. Statistical evaluation of CSS was performed by applying Kaplan Meier survival estimates, multivariate Cox regression analyses and log-rank tests. The median age of all 34 patients was 72 years (range, 51–86 years). The mean follow-up interval was 16.1 months (range, 0.7–55.6 months). Despite the fact that all patients were undergoing androgen deprivation, the mean serum FT levels for each patient varied; the mean FT concentration in the cohort was 0.328 pg/ml, ranging from 0.01–9.1 pg/ml. A notable difference with regard to CSS was observed for patients with regard to serum FT concentration; CSS was significantly longer for patients with a serum FT level below

  6. ANAEROBIC RESISTANCE TO HIGH LEVELS OF CADMIUM AND OTHER TOXIC METALS IN A FACULTATIVE ANAEROBE ISOLATED FROM PRISTINE SALT MARSH SEDIMENTS

    SciTech Connect

    SHARMA,P.K.; VAIRAVAMURTHY,A.; KIELECZAWA,J.

    1999-06-20

    The authors have isolated many Cd (II) resistant bacterial strains from relatively pristine sediments collected from salt marshes in Shelter Island, New York. Detailed studies are being performed on one isolate, strain Cd-1. Strain Cd-1 is metabolically diverse, halotolerant, Gram-negative, facultative anaerobe. It can resist high amounts of Cd (II), Cr (VI), As (V), Se (IV), Co (II), Pb (II), or Zn (II) under defined anaerobic conditions. With pyruvate as the energy source, Cd-1 can grow well at examined Cd (II) concentrations ranging up to 15 mM. It can resist Cd (II) with or without marine level NaCl concentration, under acidic or neutral conditions. It can resist Cd (II) under aerobic conditions as well. These features are novel for a heavy metal resistant bacterium.

  7. Characterization of (Ba(0.5)Sr(0.5)) TiO3 Thin Films for Ku-Band Phase Shifters

    NASA Technical Reports Server (NTRS)

    Mueller, Carl H.; VanKeuls, Fredrick W.; Romanofsky, Robert R.; Miranda, Felix A.; Warner, Joseph D.; Canedy, Chadwick L.; Ramesh, Rammamoorthy

    1999-01-01

    The microstructural properties of (Ba(0.5)Sr(0.5)TiO3) (BSTO) thin films (300, 700, and 1400 nm thick) deposited on LaAlO3 (LAO) substrates were characterized using high-resolution x-ray diffractometry. Film crystallinity was the parameter that most directly influenced tunability, and we observed that a) the crystalline quality was highest in the thinnest film and progressively degraded with increasing film thickness; and b) strain at the film/substrate interface was completely relieved via dislocation formation. Paraelectric films such as BSTO offer an attractive means of incorporating low-cost phase shifter circuitry into beam-steerable reflectarray antennas.

  8. Low β₂-adrenergic receptor level may promote development of castration resistant prostate cancer and altered steroid metabolism.

    PubMed

    Braadland, Peder Rustøen; Grytli, Helene Hartvedt; Ramberg, Håkon; Katz, Betina; Kellman, Ralf; Gauthier-Landry, Louis; Fazli, Ladan; Krobert, Kurt Allen; Wang, Wanzhong; Levy, Finn Olav; Bjartell, Anders; Berge, Viktor; Rennie, Paul S; Mellgren, Gunnar; Mælandsmo, Gunhild Mari; Svindland, Aud; Barbier, Olivier; Taskén, Kristin Austlid

    2016-01-12

    The underlying mechanisms responsible for the development of castration-resistant prostate cancer (CRPC) in patients who have undergone androgen deprivation therapy are not fully understood. This is the first study to address whether β2-adrenergic receptor (ADRB2)- mediated signaling may affect CRPC progression in vivo. By immunohistochemical analyses, we observed that low levels of ADRB2 is associated with a more rapid development of CRPC in a Norwegian patient cohort. To elucidate mechanisms by which ADRB2 may affect CRPC development, we stably transfected LNCaP cells with shRNAs to mimic low and high expression of ADRB2. Two UDP-glucuronosyltransferases, UGT2B15 and UGT2B17, involved in phase II metabolism of androgens, were strongly downregulated in two LNCaP shADRB2 cell lines. The low-ADRB2 LNCaP cell lines displayed lowered glucuronidation activities towards androgens than high-ADRB2 cells. Furthermore, increased levels of testosterone and enhanced androgen responsiveness were observed in LNCaP cells expressing low level of ADRB2. Interestingly, these cells grew faster than high-ADRB2 LNCaP cells, and sustained their low glucuronidation activity in castrated NOD/SCID mice. ADRB2 immunohistochemical staining intensity correlated with UGT2B15 staining intensity in independent TMA studies and with UGT2B17 in one TMA study. Similar to ADRB2, we show that low levels of UGT2B15 are associated with a more rapid CRPC progression. We propose a novel mechanism by which ADRB2 may affect the development of CRPC through downregulation of UGT2B15 and UGT2B17.

  9. Low β2-adrenergic receptor level may promote development of castration resistant prostate cancer and altered steroid metabolism

    PubMed Central

    Katz, Betina; Kellman, Ralf; Gauthier-Landry, Louis; Fazli, Ladan; Krobert, Kurt Allen; Wang, Wanzhong; Levy, Finn Olav; Bjartell, Anders; Berge, Viktor; Rennie, Paul S.; Mellgren, Gunnar; Mælandsmo, Gunhild Mari; Svindland, Aud; Barbier, Olivier; Taskén, Kristin Austlid

    2016-01-01

    The underlying mechanisms responsible for the development of castration-resistant prostate cancer (CRPC) in patients who have undergone androgen deprivation therapy are not fully understood. This is the first study to address whether β2-adrenergic receptor (ADRB2)- mediated signaling may affect CRPC progression in vivo. By immunohistochemical analyses, we observed that low levels of ADRB2 is associated with a more rapid development of CRPC in a Norwegian patient cohort. To elucidate mechanisms by which ADRB2 may affect CRPC development, we stably transfected LNCaP cells with shRNAs to mimic low and high expression of ADRB2. Two UDP-glucuronosyltransferases, UGT2B15 and UGT2B17, involved in phase II metabolism of androgens, were strongly downregulated in two LNCaP shADRB2 cell lines. The low-ADRB2 LNCaP cell lines displayed lowered glucuronidation activities towards androgens than high-ADRB2 cells. Furthermore, increased levels of testosterone and enhanced androgen responsiveness were observed in LNCaP cells expressing low level of ADRB2. Interestingly, these cells grew faster than high-ADRB2 LNCaP cells, and sustained their low glucuronidation activity in castrated NOD/SCID mice. ADRB2 immunohistochemical staining intensity correlated with UGT2B15 staining intensity in independent TMA studies and with UGT2B17 in one TMA study. Similar to ADRB2, we show that low levels of UGT2B15 are associated with a more rapid CRPC progression. We propose a novel mechanism by which ADRB2 may affect the development of CRPC through downregulation of UGT2B15 and UGT2B17. PMID:26646591

  10. Effects of therapeutical and reduced levels of antibiotics on the fraction of antibiotic-resistant strains of Escherichia coli in the chicken gut.

    PubMed

    van der Horst, Michael A; Fabri, Teun H; Schuurmans, J Merijn; Koenders, Belinda B; Brul, Stanley; ter Kuile, Benno H

    2013-01-01

    Development of antibiotic resistance in the microbiota of farm animals and spread of antibiotic-resistant bacteria in the agricultural sector not only threaten veterinary use of antibiotics, but jeopardize human health care as well. The effects of exposure to antibiotics on spread and development of antibiotic resistance in Escherichia coli from the chicken gut were studied. Groups of 15 pullets each were exposed under strictly controlled conditions to a 2-day course of amoxicillin, oxytetracycline, or enrofloxacin, added to the drinking water either at full therapeutic dose, 75% of that, or at the carry-over level of 2.5%. During treatment and for 12 days afterwards, the minimal inhibitory concentration (MIC) for the applied antibiotics of E. coli strains isolated from cloacal swabs was measured. The full therapeutic dose yielded the highest percentage of resistant strains during and immediately after exposure. After 12 days without antibiotics, only strains from chickens that were given amoxicillin were significantly more often resistant than the untreated control. Strains isolated from pullets exposed to carry-over concentrations were only for a few days more often resistant than those from the control. These results suggest that, if chickens must be treated with antibiotics, a short intensive therapy is preferable. Even short-term exposure to carry-over levels of antibiotics can be a risk for public health, as also under those circumstances some selection for resistance takes place.

  11. Comparative Study of Bacteremias Caused by Enterococcus spp. with and without High-Level Resistance to Gentamicin

    PubMed Central

    Caballero-Granado, Francisco Javier; Cisneros, J. M.; Luque, R.; Torres-Tortosa, M.; Gamboa, F.; Díez, F.; Villanueva, J. L.; Pérez-Cano, R.; Pasquau, J.; Merino, D.; Menchero, A.; Mora, D.; López-Ruz, M. A.; Vergara, A.; Infecciosas, for the Grupo Andaluz Para El Estudio De Las Enfermedades

    1998-01-01

    A prospective, multicenter study was carried out over a period of 10 months. All patients with clinically significant bacteremia caused by Enterococcus spp. were included. The epidemiological, microbiological, clinical, and prognostic features and the relationship of these features to the presence of high-level resistance to gentamicin (HLRG) were studied. Ninety-three patients with enterococcal bacteremia were included, and 31 of these cases were caused by HLRG (33%). The multivariate analysis selected chronic renal failure, intensive care unit stay, previous use of antimicrobial agents, and Enterococcus faecalis species as the independent risk factors that influenced the development of HLRG. The strains with HLRG showed lower levels of susceptibility to penicillin and ciprofloxacin. Clinical features (except for chronic renal failure) were similar in both groups of patients. HLRG did not influence the prognosis for patients with enterococcal bacteremia in terms of either the crude mortality rate (29% for patients with bacteremia caused by enterococci with HLRG and 28% for patients not infected with strains with HLRG) or the hospital stay after the acquisition of enterococcal bacteremia. Hemodynamic compromise, inappropriate antimicrobial therapy, and mechanical ventilation were revealed in the multivariate analysis to be the independent risk factors for mortality. Prolonged hospitalization was associated with the nosocomial acquisition of bacteremia and polymicrobial infections. PMID:9466769

  12. Transgenic tomato plants overexpressing tyramine N-hydroxycinnamoyltransferase exhibit elevated hydroxycinnamic acid amide levels and enhanced resistance to Pseudomonas syringae.

    PubMed

    Campos, Laura; Lisón, Purificación; López-Gresa, María Pilar; Rodrigo, Ismael; Zacarés, Laura; Conejero, Vicente; Bellés, José María

    2014-10-01

    Hydroxycinnamic acid amides (HCAA) are secondary metabolites involved in plant development and defense that have been widely reported throughout the plant kingdom. These phenolics show antioxidant, antiviral, antibacterial, and antifungal activities. Hydroxycinnamoyl-CoA:tyramine N-hydroxycinnamoyl transferase (THT) is the key enzyme in HCAA synthesis and is induced in response to pathogen infection, wounding, or elicitor treatments, preceding HCAA accumulation. We have engineered transgenic tomato plants overexpressing tomato THT. These plants displayed an enhanced THT gene expression in leaves as compared with wild type (WT) plants. Consequently, leaves of THT-overexpressing plants showed a higher constitutive accumulation of the amide coumaroyltyramine (CT). Similar results were found in flowers and fruits. Moreover, feruloyltyramine (FT) also accumulated in these tissues, being present at higher levels in transgenic plants. Accumulation of CT, FT and octopamine, and noradrenaline HCAA in response to Pseudomonas syringae pv. tomato infection was higher in transgenic plants than in the WT plants. Transgenic plants showed an enhanced resistance to the bacterial infection. In addition, this HCAA accumulation was accompanied by an increase in salicylic acid levels and pathogenesis-related gene induction. Taken together, these results suggest that HCAA may play an important role in the defense of tomato plants against P. syringae infection.

  13. Correlation between transcript abundance of the RB gene and the level of the RB-mediated late blight resistance in potato.

    PubMed

    Kramer, Lara C; Choudoir, Mallory J; Wielgus, Susan M; Bhaskar, Pudota B; Jiang, Jiming

    2009-04-01

    Numerous disease-resistance genes have been cloned and characterized in various plant species. Only a few of these reported genes were transcriptionally induced or had enhanced transcription upon pathogen infection. Here, we report that transcription of the RB gene, which was cloned from the wild potato species Solanum bulbocastanum and confers resistance to potato late blight, was significantly increased after inoculation with the late blight pathogen Phytophthora infestans. Different RB transgenic lines showed different levels of resistance, which were correlated with the amounts of RB transcript in the transgenic plants. Different transgenic lines also showed different patterns of RB transcription 1, 3, and 5 days after P. infestans inoculation. Interestingly, the RB gene showed a higher basal level of transcription and a more dramatic transcriptional increase upon inoculation in S. bulbocastanum than in all potato transgenic lines. Our results revealed a predictive correlation between transcript abundance of the RB gene and the level of the RB-mediated late blight resistance. High level of resistance was associated with a combination of rapid RB transcript induction immediately after pathogen infection followed by the steady production of RB transcript. Thus, the transcription level of the RB gene provides a valuable marker for selecting and deploying RB-containing potato lines for late blight control.

  14. Characterization of high-level daptomycin resistance in Viridans group Streptococci developed upon in vitro exposure to daptomycin.

    PubMed

    Akins, Ronda L; Katz, Bradley D; Monahan, Catherine; Alexander, Dylan

    2015-04-01

    Viridans group streptococci (VGS) are part of the normal flora that may cause bacteremia, often leading to endocarditis. We evaluated daptomycin against four clinical strains of VGS (MICs = 1 or 2 μg/ml) using an in vitro-simulated endocardial vegetation model, a simulated bacteremia model, and kill curves. Daptomycin exposure was simulated at 6 mg/kg of body weight and 8 mg/kg every 24 h for endocardial and bacteremia models. Total drug concentrations were used for analyses containing protein (albumin and pooled human serum), and free (unbound) drug concentrations (93% protein bound) were used for analyses not containing protein. Daptomycin MICs in the presence of protein were significantly higher than those in the absence of protein. Despite MICs below or at the susceptible breakpoint, all daptomycin regimens demonstrated limited kill in both pharmacodynamic models. A reduction of approximately 1 to 2 log10 CFU was seen for all isolates and dosages except daptomycin at 6 mg/kg, which achieved a reduction of 2.7 log10 CFU/g against one strain (Streptococcus gordonii 1649) in the endocardial model. Activity was similar in both pharmacodynamic models in the presence or absence of protein. Similar activity was noted in the kill curves over all multiples of the MIC. Regrowth by 24 h was seen even at 8× MIC. Postexposure daptomycin MICs for both pharmacodynamic models increased to >256 μg/ml for all isolates by 24 and 72 h. Despite susceptibility to daptomycin by standard MIC methods, these VGS developed high-level daptomycin resistance (HLDR) after a short duration following drug exposure not attributed to modification or inactivation of daptomycin. Further evaluation is warranted to determine the mechanism of resistance and clinical implications.

  15. A novel HSP90 inhibitor delays castrate resistant prostate cancer without altering serum PSA levels and inhibits osteoclastogenesis

    PubMed Central

    Lamoureux, Francois; Thomas, Christian; Yin, Min-Jean; Kuruma, Hidetoshi; Fazli, Ladan; Gleave, Martin E; Zoubeidi, Amina

    2015-01-01

    Purpose Prostate cancer responds initially to anti-androgen therapies, however, progression to castration resistant disease frequently occurs. Therefore there is an urgent need for novel therapeutic agents that can prevent the emergence of castration resistant prostate cancer (CRPC). Hsp90 is a molecular chaperone involved in the stability of many client proteins including Akt and androgen receptor (AR). 17-AAG have been reported to inhibit tumor growth in various cancers, however induces tumor progression in the bone microenvironment. Methods Cell growth, apoptosis, and AR transactivation were examined by crystal violet assay, flow cytometry and luciferase assays respectively. The consequence of HSP90 therapy in vivo was evaluated in LNCaP xenograft model. The consequence of PF-04928473 therapy on bone metastasis was studied using an osteoclastogenesis in vitro assay. Results PF-04928473 inhibits cell growth in a panel of prostate cancer cells, induces cell cycle arrest at sub-G1 and leads to apoptosis and increased caspase-3 activity. These biologic events were accompanied by decreased activation of Akt and Erk as well as decreased expression of Her2, and decreased AR expression and activation in vitro. In contrast to 17-AAG, PF-04928473 abrogates RANKL-induced osteoclast differentiation by affecting NF-kB activation and Src phosphorylation. Finally, PF-04929113 inhibited tumor growth and prolonged survival compared to controls. Surprisingly, PF-04929113 did not reduce serum PSA levels in vivo in parallel these decreases in tumor volume. Conclusion These data identify significant anti-cancer activity of PF-04929113 in CRPC but suggest that serum PSA may not prove useful as pharmaco-dynamic tool for this drug. PMID:21349995

  16. Characterization of High-Level Daptomycin Resistance in Viridans Group Streptococci Developed upon In Vitro Exposure to Daptomycin

    PubMed Central

    Katz, Bradley D.; Monahan, Catherine; Alexander, Dylan

    2015-01-01

    Viridans group streptococci (VGS) are part of the normal flora that may cause bacteremia, often leading to endocarditis. We evaluated daptomycin against four clinical strains of VGS (MICs = 1 or 2 μg/ml) using an in vitro-simulated endocardial vegetation model, a simulated bacteremia model, and kill curves. Daptomycin exposure was simulated at 6 mg/kg of body weight and 8 mg/kg every 24 h for endocardial and bacteremia models. Total drug concentrations were used for analyses containing protein (albumin and pooled human serum), and free (unbound) drug concentrations (93% protein bound) were used for analyses not containing protein. Daptomycin MICs in the presence of protein were significantly higher than those in the absence of protein. Despite MICs below or at the susceptible breakpoint, all daptomycin regimens demonstrated limited kill in both pharmacodynamic models. A reduction of approximately 1 to 2 log10 CFU was seen for all isolates and dosages except daptomycin at 6 mg/kg, which achieved a reduction of 2.7 log10 CFU/g against one strain (Streptococcus gordonii 1649) in the endocardial model. Activity was similar in both pharmacodynamic models in the presence or absence of protein. Similar activity was noted in the kill curves over all multiples of the MIC. Regrowth by 24 h was seen even at 8× MIC. Postexposure daptomycin MICs for both pharmacodynamic models increased to >256 μg/ml for all isolates by 24 and 72 h. Despite susceptibility to daptomycin by standard MIC methods, these VGS developed high-level daptomycin resistance (HLDR) after a short duration following drug exposure not attributed to modification or inactivation of daptomycin. Further evaluation is warranted to determine the mechanism of resistance and clinical implications. PMID:25624330

  17. Low-level laser therapy (LLLT) associated with aerobic plus resistance training to improve inflammatory biomarkers in obese adults.

    PubMed

    da Silveira Campos, Raquel Munhoz; Dâmaso, Ana Raimunda; Masquio, Deborah Cristina Landi; Aquino, Antonio Eduardo; Sene-Fiorese, Marcela; Duarte, Fernanda Oliveira; Tock, Lian; Parizotto, Nivaldo Antonio; Bagnato, Vanderlei Salvador

    2015-07-01

    Recently, investigations suggest the benefits of low-level laser (light) therapy (LLLT) in noninvasive treatment of cellulite, improvement of body countering, and control of lipid profile. However, the underlying key mechanism for such potential effects associated to aerobic plus resistance training to reduce body fat and inflammatory process, related to obesity in women still unclear. The purpose of the present investigation was to evaluate the effects of combined therapy of LLLT and aerobic plus resistance training in inflammatory profile and body composition of obese women. For this study, it involved 40 obese women with age of 20-40 years. Inclusion criteria were primary obesity and body mass index (BMI) greater than 30 kg/m(2) and less than 40 kg/m(2). The voluntaries were allocated in two different groups: phototherapy group and SHAM group. The interventions consisted on physical exercise training and application of phototherapy (808 nm), immediately after the physical exercise, with special designed device. Proinflammatory/anti-inflammatory adipokines were measured. It was showed that LLLT associated to physical exercise is more effective than physical exercise alone to increase adiponectin concentration, an anti-inflammatory adipokine. Also, it showed reduced values of neck circumference (cm), insulin concentration (μU/ml), and interleukin-6 (pg/ml) in LLLT group. In conclusion, phototherapy can be an important tool in the obesity, mostly considering its potential effects associated to exercise training in attenuating inflammation in women, being these results applicable in the clinical practices to control related risk associated to obesity.

  18. Transcriptomic responses to emamectin benzoate in Pacific and Atlantic Canada salmon lice Lepeophtheirus salmonis with differing levels of drug resistance

    PubMed Central

    Sutherland, Ben J G; Poley, Jordan D; Igboeli, Okechukwu O; Jantzen, Johanna R; Fast, Mark D; Koop, Ben F; Jones, Simon R M

    2015-01-01

    Salmon lice Lepeophtheirus salmonis are an ecologically and economically important parasite of wild and farmed salmon. In Scotland, Norway, and Eastern Canada, L. salmonis have developed resistance to emamectin benzoate (EMB), one of the few parasiticides available for salmon lice. Drug resistance mechanisms can be complex, potentially differing among populations and involving multiple genes with additive effects (i.e., polygenic resistance). Indicators of resistance development may enable early detection and countermeasures to avoid the spread of resistance. Here, we collect sensitive Pacific L. salmonis and sensitive and resistant Atlantic L. salmonis from salmon farms, propagate in laboratory (F1), expose to EMB in bioassays, and evaluate either baseline (Atlantic only) or induced transcriptomic differences between populations. In all populations, induced responses were minor and a cellular stress response was not identified. Pacific lice did not upregulate any genes in response to EMB, but downregulated degradative enzymes and transport proteins at 50 ppb EMB. Baseline differences between sensitive and now resistant Atlantic lice were much greater than responses to exposures. All resistant lice overexpressed degradative enzymes, and resistant males, the most resistant group, overexpressed collagenases to the greatest extent. These results indicate an accumulation of baseline expression differences related to resistance. PMID:25685190

  19. Prevalence of the metabolic syndrome, insulin resistance index, leptin and thyroid hormone levels in the general population of Merida (Venezuela).

    PubMed

    Uzcátegui, Euderruh; Valery, Lenin; Uzcátegui, Lilia; Gómez Pérez, Roald; Marquina, David; Baptista, Trino

    2015-06-01

    The metabolic syndrome (MetSyn) is a significant risk factor for cardiovascular events, but scarce information exists about its frequency in Venezuela. In this cross-sectional study, we quantified the prevalence of the MetSyn in a probabilistic, stratified sample of 274 subjects aged > or =18 years from the Libertador district in Merida, Venezuela. Secondary outcomes were the measurement of thyroid hormones (free T4 and TSH), leptin levels, and insulin resistance index (HOMA2-IR). The frequency of MetSyn (percentage +/- 95% confidence interval) according to several diagnostic criteria was as follows: National Cholesterol Education Panel (NCEP, original): 27.4% (22.1-32.7); modified NCEP: 31.8% (26.3-37.3); International Diabetes Federation: 40.9% (35.1-46.7); Latin American Diabetes Association: 27% (21.7-32.3), and Venezuelan criteria: 31.8% (26.3-37.3). The MetSyn was more frequent in males than in females with most diagnostic criteria. The estimated prevalence of type 2 diabetes mellitus was 2.9% either according to the patients' self reports or to fasting glucose level found to be above 126 mg/dL. Abnormal HOMA2-IR index, free T4 and TSH (above the 95th percentile) were detected in 4.5%, 4.4% and 5.1% of the sample, respectively. Free T4 and TSH levels below the 5th percentile were detected in 4.4% and 4.7% of subjects respectively. These values are presented for comparisons with forthcoming studies in specific clinical populations. While studies are being conducted about the different definitions of the MetSyn in Venezuela, we recommend analyzing and publishing local research data with all the available criteria so as to allow comparisons with the results already reported in the literature.

  20. Serum γ-glutamyl Transferase Levels, Insulin Resistance and Liver Fibrosis in Patients with Chronic Liver Diseases

    PubMed Central

    Petta, Salvatore; Macaluso, Fabio Salvatore; Barcellona, Maria Rosa; Cammà, Calogero; Cabibi, Daniela; Di Marco, Vito; Craxì, Antonio

    2012-01-01

    Background and Aims Serum levels of γ-glutamyl-transpeptidase(γ-GT) were associated with liver disease severity and metabolic alterations, which in turn are able to affect hepatic damage. In patients with nonalcoholic fatty liver disease (NAFLD), genotype 1 chronic hepatitis C (G1CHC) and chronic hepatitis B (CHB), we assessed the link between liver fibrosis and γ-GT serum levels, and we evaluated if normal or high γ-GT serum levels affect the association between insulin resistance (IR) and severity of liver fibrosis. Methods 843 consecutive patients with chronic liver disease (CLD)(193 NAFLD, 481 G1CHC, 169 CHB) were evaluated by liver biopsy (Kleiner and Scheuer scores) and clinical and metabolic measurements. IR was diagnosed if HOMA>3. A serum γ-GT concentration of >36 IU/L in females and >61 IU/L in males was considered the threshold value for identifying high levels of γ-GT. Results By multivariate logistic regression analysis, abnormal γ-GT serum levels were independently linked to severe liver fibrosis in patients with NAFLD (OR2.711,CI1.120–6.564,p = 0.02), G1CHC (OR3.461,CI2.138–5.603,p<0.001) and CHB (OR2.778,CI1.042–7.414,p = 0.04), together with IR and liver necroinflammation, and with a negative predictive value>80%. Interestingly, among patients with high or normal γ-GT values, even if IR prevalence was significantly higher in patients with severe fibrosis compared to those without, IR remained significantly associated with severe fibrosis in patients with abnormal γ-GT values only (OR4.150,CI1.079–15.970,p = 0.03 for NAFLD; OR2.250,CI1.211–4.181,p = 0.01 for G1CHC; OR3.096,CI2.050–34.220,p = 0.01 for CHB). Conclusions In patients with CLD, IR is independently linked to liver fibrosis only in patients with abnormal γ-GT values, without differences according to liver disease etiology, and suggesting a role of γ-GT as a marker of metabolic-induced liver damage. These data could be useful for the clinical and

  1. Dielectric properties of barium strontium titanate (BST) thin films and phase shifters based on BST thin films

    NASA Astrophysics Data System (ADS)

    Zhou, Xiaoyuan

    crystallized. BST thin films were then deposited on the Si/SiO2 substrates with the similar technology. Fourthly, we have fabricated tunable microwave phase shifters on BST/LSAT substrates with good features like high reliability, simple configuration and large phase shift per unit area. By carefully optimizing the processing, prototype devices with following specifications were obtained: work frequency = 9 GHz, phase shift up to 70°, figure-of-merit = 60°/dB, insertion loss (S21) = -1.3 dB and return loss ( S11) = -14.3 dB.

  2. SU-E-T-189: Commission Range Shifter On a Spot Scanning Proton System Using Raystation Treatment Planning System

    SciTech Connect

    Ding, X; Wu, H; Rosen, L

    2015-06-15

    Purpose: To treat superficial target e.g. chest wall, head&neck or cranial cases, we commissioned two range shifter(RS) in Raystation4.0 with 7.37cm(RS1) and 4.1cm(RS2) Water Equivalent Thickness(WET) respectively. However, current beam model has limitations due to the secondary scattered proton. This study provides a detailed and critical commission data and provides suggestions for using RS in clinic. Methods: RS’ WET was verified by Multi-Layer Ionization Chamber from 120MeV to 226.7MeV before TPS modeling. Spot characteristics were measured using 2D scintillate detector at ISO with different air gap. A 8×8×10cm3 cube is created in 8cm depth of water to verify the absolute dose accuracy. Plans were created with different air gap using both RS. Absolute dose verification was measured along the central axis from distal end to surface using PPC05. 10 clinical RS2 plans were measured using MatriXXPT in 3 planes (proximal, distal and midSOBP). Results: RS material’s proton stopping power is energy dependent(from 70MeV to 226.7MeV) ranging from 7.42 to 7.31cm and from 4.10 to 4.03cm respectively. We chose 7.37cm (RS1) and 4.10cm (RS2) to favor the low and median proton energy. With different air gap(3cm to 32cm), spot size expands from 3.2mm to 5.5mm(RS1) and from 3.1mm to 4.1mm(RS2) respectively(226.7MeV in air, 1-sigma). For the absolute dose verification, the larger air gap and shallower depth causes larger discrepancy between TPS and measurements. All 10 clinical plans with 5–10cm air gap passed gamma index 95% with 3%/3mm criteria and outputs differences were within 3%. Conclusion: We strongly recommend each institution to verify the WET independently and choose the value to fit the clinical needs. To minimize the output difference in Raystation4.0 while avoid potential collision to the patient, we recommend to use 5–10cm air gap to minimize the output difference within 2% and preferably use RS with smaller WET if possible.

  3. Genotypic susceptibility testing of Mycobacterium tuberculosis isolates for amikacin and kanamycin resistance by use of a rapid sloppy molecular beacon-based assay identifies more cases of low-level drug resistance than phenotypic Lowenstein-Jensen testing.

    PubMed

    Chakravorty, Soumitesh; Lee, Jong Seok; Cho, Eun Jin; Roh, Sandy S; Smith, Laura E; Lee, Jiim; Kim, Cheon Tae; Via, Laura E; Cho, Sang-Nae; Barry, Clifton E; Alland, David

    2015-01-01

    Resistance to amikacin (AMK) and kanamycin (KAN) in clinical Mycobacterium tuberculosis strains is largely determined by specific mutations in the rrs gene and eis gene promoter. We developed a rapid, multiplexed sloppy molecular beacon (SMB) assay to identify these mutations and then evaluated assay performance on 603 clinical M. tuberculosis DNA samples collected in South Korea. Assay performance was compared to gold-standard phenotypic drug susceptibility tests, including Lowenstein-Jensen (LJ) absolute concentration, mycobacterial growth indicator tubes (MGIT), and TREK Sensititre MycoTB MIC plate (MycoTB) methods. Target amplicons were also tested for mutations by Sanger sequencing. The SMB assay correctly detected 115/116 mutant and mixed sequences and 487/487 wild-type sequences (sensitivity and specificity of 99.1 and 100%, respectively). Using the LJ method as the reference, sensitivity and specificity for AMK resistance were 92.2% and 100%, respectively, and sensitivity and specificity for KAN resistance were 87.7% and 95.6%, respectively. Mutations in the rrs gene were unequivocally associated with high-level cross-resistance to AMK and KAN in all three conventional drug susceptibility testing methods. However, eis promoter mutations were associated with KAN resistance using the MGIT or MycoTB methods but not the LJ method. No testing method associated eis promoter mutations with AMK resistance. Among the discordant samples with AMK and/or KAN resistance but wild-type sequence at the target genes, we discovered four new mutations in the whiB7 5' untranslated region (UTR) in 6/22 samples. All six samples were resistant only to KAN, suggesting the possible role of these whiB7 5' UTR mutations in KAN resistance.

  4. Expression levels of antimicrobial peptide tachyplesin I in transgenic Ornithogalum lines affect the resistance to Pectobacterium infection.

    PubMed

    Lipsky, Alexander; Joshi, Janak Raj; Carmi, Nir; Yedidia, Iris

    2016-11-20

    The genus Ornithogalum includes several ornamental species that suffer substantial losses from bacterial soft rot caused by Pectobacteria. The absence of effective control measures for use against soft rot bacteria led to the initiation of a project in which a small antimicrobial peptide from an Asian horseshoe crab, tachyplesin (tpnI), was introduced into two commercial cultivars: O. dubium and O. thyrsoides. Disease severity and bacterial colonization were examined in transgenic lines expressing this peptide. Disease resistance was evaluated in six lines of each species by measuring bacterial proliferation in the plant tissue. Three transgenic lines of each species were subjected to further analysis in which the expression level of the transgene was evaluated using RT-PCR and qRT-PCR. The development of disease symptoms and bacterial colonization of the plant tissue were also examined using GFP-expressing strain of P. carotovorum subsp. brasiliense Pcb3. Confocal-microscopy imaging revealed significantly reduced quantities of bacterial cells in the transgenic plant lines that had been challenged with the bacterium. The results clearly demonstrate that tpnI expression reduces bacterial proliferation, colonization and disease symptom (reduced by 95-100%) in the transgenic plant tissues. The quantity of tpnI transcripts, as measured by qRT-PCR, was negatively correlated with the protection afforded to the plants, as measured by the reduced severity of disease symptoms in the tissue.

  5. Differential genomic responses in old vs. young humans despite similar levels of modest muscle damage after resistance loading

    PubMed Central

    Thalacker-Mercer, Anna E.; Dell'Italia, Louis J.; Cui, Xiangqin; Cross, James M.

    2010-01-01

    Across numerous model systems, aging skeletal muscle demonstrates an impaired regenerative response when exposed to the same stimulus as young muscle. To better understand the impact of aging in a human model, we compared changes to the skeletal muscle transcriptome induced by unaccustomed high-intensity resistance loading (RL) sufficient to cause moderate muscle damage in young (37 yr) vs. older (73 yr) adults. Serum creatine kinase was elevated 46% 24 h after RL in all subjects with no age differences, indicating similar degrees of myofiber membrane wounding by age. Despite this similarity, from genomic microarrays 318 unique transcripts were differentially expressed after RL in old vs. only 87 in young subjects. Follow-up pathways analysis and functional annotation revealed among old subjects upregulation of transcripts related to stress and cellular compromise, inflammation and immune responses, necrosis, and protein degradation and changes in expression (up- and downregulation) of transcripts related to skeletal and muscular development, cell growth and proliferation, protein synthesis, fibrosis and connective tissue function, myoblast-myotube fusion and cell-cell adhesion, and structural integrity. Overall the transcript-level changes indicative of undue inflammatory and stress responses in these older adults were not mirrored in young subjects. Follow-up immunoblotting revealed higher protein expression among old subjects for NF-κB, heat shock protein (HSP)70, and IL-6 signaling [total and phosphorylated signal transducer and activator of transcription (STAT)3 at Tyr705]. Together, these novel findings suggest that young and old adults are equally susceptible to RL-mediated damage, yet the muscles of older adults are much more sensitive to this modest degree of damage—launching a robust transcriptome-level response that may begin to reveal key differences in the regenerative capacity of skeletal muscle with advancing age. PMID:19903761

  6. Domestication in Murtilla (Ugni molinae) Reduced Defensive Flavonol Levels but Increased Resistance Against a Native Herbivorous Insect.

    PubMed

    Chacón-Fuentes, Manuel; Parra, Leonardo; Rodriguez-Saona, Cesar; Seguel, Ivette; Ceballos, Ricardo; Quiroz, Andres

    2015-06-01

    Plant domestication can have negative consequences for defensive traits against herbivores, potentially reducing the levels of chemical defenses in plants and consequently their resistance against herbivores. We characterized and quantified the defensive flavonols from multiple cultivated ecotypes with wild ancestors of murtilla, Ugni molinae Turcz, an endemic plant from Chile, at different times of the year, and examined their effects on a native insect herbivore, Chilesia rudis Butler (Lepidoptera: Arctiidae). We hypothesized that domestication results in a decrease in flavonol levels in U. molinae plants, and that this negatively affected C. rudis performance and preference. Ethanolic extracts were made from leaves, stems, and fruit of murtilla plants for flavonol analysis. Flavonols identified were kaempferol, quercetin, rutin, and quercetin 3-D-β-glucoside, the last two being the most abundant. More interestingly, we showed differences in flavonol composition between wild and cultivated U. molinae that persisted for most of the year. Relative amounts of all four flavonols were higher in wild U. molinae leaves; however, no differences were found in the stem and fruit between wild and cultivated plants. In choice and no-choice assays, C. rudis larvae gained more mass on, and consumed more leaf material of, wild as compared with cultivated U. molinae plants. Moreover, when applied to leaves, larvae ate more leaf material with increasing concentrations of each flavonol compound. Our study demonstrates that domestication in U. molinae reduced the amount of flavonols in leaves as well as the performance and preference of C. rudis, indicating that these compounds stimulate feeding of C. rudis.

  7. Fermi-level depinning and contact resistance reduction in metal/n-Ge junctions by insertion of W-encapsulating Si cluster films

    SciTech Connect

    Okada, Naoya; Uchida, Noriyuki; Kanayama, Toshihiko

    2014-02-10

    We demonstrate Fermi-level depinning in metal/Ge junctions and a significant reduction of specific contact resistivity of n-Ge by inserting an ultra-thin semiconducting Si-rich W silicide film (WSi{sub n}, n = 12–14) composed of W-encapsulating Si clusters. Dependence of the specific contact resistivity on the electron Schottky barrier height followed the ideal exponential relation for various contact metal species. This result indicates that the insertion of the WSi{sub n} film provides a negligible contribution to contact resistivity because its tunneling resistance is very low owing to the low offset of the conduction band edge of Ge.

  8. Herd-level relationship between antimicrobial use and presence or absence of antimicrobial resistance in gram-negative bovine mastitis pathogens on Canadian dairy farms.

    PubMed

    Saini, Vineet; McClure, J T; Scholl, Daniel T; DeVries, Trevor J; Barkema, Herman W

    2013-08-01

    Concurrent data on antimicrobial use (AMU) and resistance are needed to contain antimicrobial resistance (AMR) in bacteria. The present study examined a herd-level association between AMU and AMR in Escherichia coli (n=394) and Klebsiella species (n=139) isolated from bovine intramammary infections and mastitis cases on 89 dairy farms in 4 regions of Canada [Alberta, Ontario, Québec, and Maritime Provinces (Prince Edward Island, Nova Scotia, and New Brunswick)]. Antimicrobial use data were collected using inventory of empty antimicrobial containers and antimicrobial drug use rate was calculated to quantify herd-level AMU. Minimum inhibitory concentrations (MIC) were determined using Sensititre National Antimicrobial Resistance Monitoring System (NARMS) gram-negative MIC plate (Trek Diagnostic Systems Inc., Cleveland, OH). Isolates were classified as susceptible, intermediate, or resistant. Intermediate and resistant category isolates were combined to form an AMR category, and multivariable logistic regression models were built to determine herd-level odds of AMR to tetracycline, ampicillin, cefoxitin, chloramphenicol, trimethoprim-sulfamethoxazole combination, sulfisoxazole, streptomycin and kanamycin in E. coli isolates. In the case of Klebsiella species isolates, logistic regression models were built for tetracycline and sulfisoxazole; however, no associations between AMU and AMR in Klebsiella species were observed. Ampicillin-intermediate or -resistant E. coli isolates were associated with herds that used intramammarily administered cloxacillin, penicillin-novobiocin combination, and cephapirin used for dry cow therapy [odds ratios (OR)=26, 32, and 189, respectively], and intramammary ceftiofur administered for lactating cow therapy and systemically administered penicillin (OR=162 and 2.7, respectively). Use of systemically administered penicillin on a dairy farm was associated with tetracycline and streptomycin-intermediate or -resistant E. coli isolates (OR=5

  9. The effects of long-term resistance exercise on the relationship between neurocognitive performance and GH, IGF-1, and homocysteine levels in the elderly

    PubMed Central

    Tsai, Chia-Liang; Wang, Chun-Hao; Pan, Chien-Yu; Chen, Fu-Chen

    2015-01-01

    This study aimed to investigate the effects of a long-term resistance exercise intervention on executive functions in healthy elderly males, and to further understand the potential neurophysiological mechanisms mediating the changes. The study assessed forty-eight healthy elderly males randomly assigned to exercise (n = 24) or control (n = 24) groups. The assessment included neuropsychological and neuroelectric measures during a variant of the oddball task paradigm, as well as growth hormone (GH), insulin-like growth factor-1 (IGF-1), and homocysteine levels at baseline and after either a 12 month intervention of resistance exercise training or control period. The results showed that the control group had a significantly lower accuracy rate and smaller P3a and P3b amplitudes in the oddball condition after 12 months. The exercise group exhibited improved reaction times (RTs), sustained P3a and P3b amplitudes, increased levels of serum IGF-1, and decreased levels of serum homocysteine. The changes in IGF-1 levels were significantly correlated with the changes in RT and P3b amplitude of the oddball condition in the exercise group. In conclusion, significantly enhanced serum IGF-1 levels after 12 months of resistance exercise were inversely correlated with neurocognitive decline in the elderly. These findings suggest that regular resistance exercise might be a promising strategy to attenuate the trajectory of cognitive aging in healthy elderly individuals, possibly mediated by IGF-1. PMID:25713518

  10. Effect of aerobic training and resistance training on circulating irisin level and their association with change of body composition in overweight/obese adults: a pilot study.

    PubMed

    Kim, H-J; Lee, H-J; So, B; Son, J S; Yoon, D; Song, W

    2016-06-20

    The novel myokine irisin has been reported as a therapeutic target for metabolic disease. The objective of this study is to reveal the effects of aerobic training (AT) and resistance training (RT) on circulating irisin levels and their associations with change of body composition in overweight/obese adults. Twenty eight overweight/obese adults (BMI>23 kg/m(2)) were included in this study and compared before and after 8 weeks of exercise program (60 min/day, 5 times in a week). The subjects, in both aerobic and resistance training, showed significant improvement in anthropometric parameters and exercise capacities including maximal oxygen uptake and muscle strength. Interestingly, the circulating irisin was significantly increased in resistance training group (p=0.002) but not in aerobic training (p=0.426) compared to control group. In addition, we found the positive correlation between change of the circulating irisin and muscle mass (r=0.432, p=0.022) and the negative correlation between change of the circulating irisin and fat mass (r=-0.407, p=0.031). In the present pilot study, we found that circulating irisin level was increased by 8 weeks of resistance training in overweight/obese adults, suggesting that resistance training could be the efficient exercise type in overweight/obese considering positive change of body composition concomitant with increase of irisin levels.

  11. Reduced Systemic Levels of IL-10 Are Associated with the Severity of Obstructive Sleep Apnea and Insulin Resistance in Morbidly Obese Humans

    PubMed Central

    Leon-Cabrera, Sonia; Arana-Lechuga, Yoaly; Esqueda-León, Enrique; Terán-Pérez, Guadalupe; Gonzalez-Chavez, Antonio; Velázquez Moctezuma, Javier

    2015-01-01

    Obstructive sleep apnea (OSA) has been related to elevation of inflammatory cytokines and development of insulin resistance in morbidly obese (MO) subjects. However, it is still unclear whether the systemic concentration of anti-inflammatory mediators is also affected in MO subjects directly related to the severity of OSA and level of insulin resistance. Normal weight and MO subjects were subjected to overnight polysomnography in order to establish the severity of OSA, according to the apnea-hypopnea index (AHI). Blood samples were obtained for estimation of total cholesterol and triglycerides, insulin, glucose, insulin resistance, tumor necrosis factor alpha (TNF-α), interleukin 12 (IL12), and interleukin 10 (IL-10). Serum levels of IL-10 were significantly lower in MO subjects with OSA than in MO and control individuals without OSA. Besides being inversely associated with serum TNF-α and IL-12, decreased IL-10 levels were significantly related to increased AHI, hyperinsulinemia, and insulin resistance. Serum IL-10 is significantly reduced in morbidly obese subjects with severe OSA while also showing a clear relationship with a state of hyperinsulinemia and insulin resistance probably regardless of obesity in the present sample. It may be of potential clinical interest to identify the stimulatory mechanisms of IL-10 in obese individuals with OSA. PMID:25944984

  12. Identification of QTL controlling high levels of partial resistance to Fusarium solani f. sp. pisi in pea

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fusarium root rot is a common biotic restraint on pea yields worldwide and genetic resistance is the most feasible method for improving pea production. This study was conducted to discover quantitative trait loci (QTL) controlling genetic partial resistance to Fusarium root rot caused by Fusarium s...

  13. Reduced levels of membrane-bound alkaline phosphatase are common to lepidopteran strains resistant to Cry toxins from Bacillus thuringiensis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Development of insect resistance is one of the main concerns with the use of transgenic crops expressing Cry toxins from the bacterium Bacillus thuringiensis. Biomarkers for development of sensitive DNA-based methods to detect and monitor evolution of resistance to Bt toxins are currently needed. ...

  14. Greater physical activity levels during pregnancy are associated with lower inflammation and insulin resistance in obese women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Compared to lean pregnant women, obese women develop greater insulin resistance and systemic inflammation during pregnancy. Identifying lifestyle factors that can reduce the metabolic effect of obesity during pregnancy is critical to protect both the mother and the fetus from insulin resistance and ...

  15. Abamectin is metabolized by CYP392A16, a cytochrome P450 associated with high levels of acaricide resistance in Tetranychus urticae.

    PubMed

    Riga, M; Tsakireli, D; Ilias, A; Morou, E; Myridakis, A; Stephanou, E G; Nauen, R; Dermauw, W; Van Leeuwen, T; Paine, M; Vontas, J

    2014-03-01

    Abamectin is one of the most important insecticides worldwide. It is used against major agricultural pests and insects of public health importance, as well as against endoparasites in animal health. Abamectin has been used successfully for the control of the spider mite Tetranychus urticae, a major agricultural pest with global distribution, an extremely diverse host range, and a remarkable ability to develop resistance against insecticides including abamectin. Target site resistance mutations may explain a large part of resistance, although genetic evidence and transcriptomic data indicated that additional mechanisms may also be implicated in the abamectin resistant phenotype. To investigate a functional link between cytochrome P450-mediated metabolism and abamectin resistance, we recombinantly expressed three cytochrome P450s (CYP392A16, CYP392D8 and CYP392D10) that have been associated with high levels of abamectin resistance in a resistant T. urticae strain isolated from Greece. CYP392A16 was expressed predominately in its P450 form however, both CYP392D8 and CYP392D10 were expressed predominately as P420, despite optimization efforts on expression conditions. CYP392A16 catalyses the hydroxylation of abamectin (Kcat=0.54 pmol/min/pmol P450; Km=45.9 μM), resulting in a substantially less toxic compound as confirmed by bioassays with the partially purified metabolite. However, CYP392A16 did not metabolize hexythiazox, clofentezine and bifenthrin, active ingredients that also showed reduced toxicity in the abamectin resistant strain. Among a number of fluorescent and luminescent substrates screened, Luciferin-ME EGE was preferentially metabolized by CYP392A16, and it may be a potential diagnostic probe for metabolic resistance detection and monitoring.

  16. Effects of dietary levels of vitamin A on growth, hematology, immune response and resistance of Nile tilapia (Oreochromis niloticus) to Streptococcus iniae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was conducted to evaluate the effect of supplemental levels of vitamin A (0, 2,500, 5,000, 10,000, and 20,000 IU/kg diet) on the growth performance, hematology, immune response and resistance of Nile tilapia, Oreochromis niloticus to Streptococcus iniae challenge. Each diet was fed to Nil...

  17. Inheritance of high levels of resistance to common bacterial blight caused by Xanthomonas Axonopodis pv. Phaseoli in common bean (Phaseolus vulgaris L.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Common bacterial blight caused by the pathogen Xanthomonas axonopodis pv. phaseoli (Xap) is an important biotic factor limiting common bean (Phaseolus vulgaris L.) production. A few interspecific bean breeding lines such as VAX 6 exhibit a high level of resistance to a wide range of Xap strains repr...

  18. Rifabutin and rifampin resistance levels and associated rpoB mutations in clinical isolates of Mycobacterium tuberculosis complex.

    PubMed

    Berrada, Zenda L; Lin, Shou-Yean Grace; Rodwell, Timothy C; Nguyen, Duylinh; Schecter, Gisela F; Pham, Lucy; Janda, J Michael; Elmaraachli, Wael; Catanzaro, Antonino; Desmond, Edward

    2016-06-01

    Cross-resistance in rifamycins has been observed in rifampin (RIF)-resistant Mycobacterium tuberculosis complex isolates; some rpoB mutations do not confer broad in vitro rifamycin resistance. We examined 164 isolates, of which 102 were RIF-resistant, for differential resistance between RIF and rifabutin (RFB). A total of 42 unique single mutations or combinations of mutations were detected. The number of unique mutations identified exceeded that reported in any previous study. RFB and RIF MICs up to 8 μg/mL by MGIT 960 were studied; the cut-off values for susceptibility to RIF and RFB were 1 μg/mL and 0.5 μg/mL, respectively. We identified 31 isolates resistant to RIF but susceptible to RFB with the mutations D516V, D516F, 518 deletion, S522L, H526A, H526C, H526G, H526L, and two dual mutations (S522L + K527R and H526S + K527R). Clinical investigations using RFB to treat multidrug-resistant tuberculosis cases harboring those mutations are recommended.

  19. Obesity-associated insulin resistance is correlated to adipose tissue vascular endothelial growth factors and metalloproteinase levels

    PubMed Central

    2012-01-01

    Background The expansion of adipose tissue is linked to the development of its vasculature, which appears to have the potential to regulate the onset of obesity. However, at present, there are no studies highlighting the relationship between human adipose tissue angiogenesis and obesity-associated insulin resistance (IR). Results Our aim was to analyze and compare angiogenic factor expression levels in both subcutaneous (SC) and omentum (OM) adipose tissues from morbidly obese patients (n = 26) with low (OB/L-IR) (healthy obese) and high (OB/H-IR) degrees of IR, and lean controls (n = 17). Another objective was to examine angiogenic factor correlations with obesity and IR. Here we found that VEGF-A was the isoform with higher expression in both OM and SC adipose tissues, and was up-regulated 3-fold, together with MMP9 in OB/L-IR as compared to leans. This up-regulation decreased by 23% in OB/-H-IR compared to OB/L-IR. On the contrary, VEGF-B, VEGF-C and VEGF-D, together with MMP15 was down-regulated in both OB/H-IR and OB/L-IR compared to lean patients. Moreover, MMP9 correlated positively and VEGF-C, VEGF-D and MMP15 correlated negatively with HOMA-IR, in both SC and OM. Conclusion We hereby propose that the alteration in MMP15, VEGF-B, VEGF-C and VEGF-D gene expression may be caused by one of the relevant adipose tissue processes related to the development of IR, and the up-regulation of VEGF-A in adipose tissue could have a relationship with the prevention of this pathology. PMID:22471305

  20. New system based on site-directed mutagenesis for highly accurate comparison of resistance levels conferred by SHV beta-lactamases.

    PubMed Central

    Nüesch-Inderbinen, M T; Hächler, H; Kayser, F H

    1995-01-01

    We developed a system based on site-directed mutagenesis that allows a precise comparison of SHV enzymes under isogenic conditions. In addition, the influences of two different, naturally occurring promoters were examined for each SHV derivative. The system comprised two separately cloned DNA fragments, each the size of 3.6 kb. Both fragments encoded an SHV gene originating from clinical isolates but with different promoters. The structural genes were made identical by site-directed mutagenesis. Other mutations were then introduced into both fragments by means of site-directed mutagenesis, resulting in the SHV derivatives SHV-1, SHV-2, SHV-2a, SHV-3, and SHV-5. The amino acid exchange of glutamic acid at position 235 for lysine in SHV-5 resulted in the highest resistance levels. SHV-3, differing from SHV-2 by the exchange of arginine at position 201 for leucine and previously described as indistinguishable from SHV-2, was shown to cause slightly higher resistance to ceftazidime and lower resistance to ceftriaxone, cefotaxime, and cefepime than SHV-2. The point mutation in SHV-2a, with the leucine-to-glutamine replacement at the unusual position 31, previously considered almost insignificant, proved to increase resistance to ceftazidime but reduced the MICs of all other cephalosporins tested when compared with those for SHV-2. For all clones harboring SHV derivatives, resistance was increased by a stronger promoter, in some cases masking the effect of the point mutation itself and demonstrating the importance of regulatory mechanisms of resistance. PMID:7486909

  1. High-level tolerance to triclosan may play a role in Pseudomonas aeruginosa antibiotic resistance in immunocompromised hosts: evidence from outbreak investigation

    PubMed Central

    2012-01-01

    Background and methods Pseudomonas aeruginosa is a major infectious threat to immunocompromised patients. We recently reported a fatal epidemic of multidrug-resistant P. aeruginosa in an onchoematology unit, linked to massive contamination of a triclosan-based disinfectant. The aim of this study is to evaluate the antimicrobial activity of triclosan and chlorhexidine digluconate against the epidemic strain of P. aeruginosa, to confirm the hypothesis that the soap dispenser acted as a continuous source of the infection during the outbreak, and to explore the potential role of triclosan in increasing the level of resistance to selected antibiotics. Susceptibility tests and time-kill assays for disinfectans were performed using two commercial formulations containing triclosan and chlorhexidine digluconate, respectively. Antibiotic susceptibility testing was performed by the broth microdilution method. Findings The P. aeruginosa epidemic strain exhibited an extremely high level of triclosan resistance (apparent MIC = 2,125 mg/L), while it was markedly susceptible to chlorhexidine digluconate (apparent MIC = 12.5 mg/L). Upon gradual adaptation to triclosan, the epidemic strain survived for a long period (> 120 h) in the presence of 3,400 mg/L (equivalent to 1.6 × MIC) of triclosan, concomitantly increasing the resistance to six antibiotics that are typical substrates of drug efflux pumps of the resistance nodulation division family. This effect was reversed by efflux pump inhibitors. Conclusions The epidemic P. aeruginosa strain was resistant to triclosan and its previous exposure to triclosan increases antibiotic resistance, likely through active efflux mechanisms. Since P. aeruginosa can become tolerant to elevated triclosan concentrations, the use of triclosan-based disinfectants should be avoided in those healthcare settings hosting patients at high risk for P. aeruginosa infection. PMID:22260715

  2. Cerebrospinal Fluid Levels of Leptin, Proopiomelanocortin, and Agouti-Related Protein in Human Pregnancy: Evidence for Leptin Resistance

    PubMed Central

    Page-Wilson, Gabrielle; Reitman-Ivashkov, Elena; Meece, Kana; White, Anne; Rosenbaum, Michael; Smiley, Richard M.

    2013-01-01

    Context: Leptin suppresses appetite by modulating the expression of hypothalamic neuropeptides including proopiomelanocortin (POMC) and agouti-related peptide (AgRP). Yet during pregnancy, caloric consumption increases despite elevated plasma leptin levels. Design and Participants: To investigate this paradox, we measured leptin and soluble leptin receptor in plasma and leptin, POMC, and AgRP in cerebrospinal fluid (CSF) from 21 fasting pregnant women before delivery by cesarean section at a university hospital and from 14 fasting nonpregnant women. Results: Prepregnancy body mass index was 24.6 ± 1.1 (se) vs. 31.3 ± 1.3 at term vs. 26.5 ± 1.6 kg/m2 in controls. Plasma leptin (32.9 ± 4.6 vs. 16.7 ± 3.0 ng/ml) and soluble leptin receptor (30.9 ± 2.3 vs. 22.1 ± 1.4 ng/ml) levels were significantly higher in pregnant women. However, mean CSF leptin did not differ between the two groups (283 ± 34 vs. 311 ± 32 pg/ml), consistent with a relative decrease in leptin transport into CSF during pregnancy. Accordingly, the CSF/plasma leptin percentage was 1.0 ± 0.01% in pregnant subjects vs. 2.1 ± 0.2% in controls (P < 0.0001). Mean CSF AgRP was significantly higher in pregnant subjects (32.3 ± 2.7 vs. 23.5 ± 2.5 pg/ml; P = 0.03). Mean CSF POMC was not significantly different in pregnant subjects (200 ± 13.6 vs. 229 ± 17.3 fmol/ml; P = 0.190). However, the mean AgRP/POMC ratio was significantly higher among pregnant women (P = 0.003), consistent with an overall decrease in melanocortin tone favoring increased food intake during pregnancy. Conclusions: These data demonstrate that despite peripheral hyperleptinemia, positive energy balance is achieved during pregnancy by a relative decrease in central leptin concentrations and resistance to leptin's effects on target neuropeptides that regulate energy balance. PMID:23118421

  3. A three amino acid deletion in the transmembrane domain of the nicotinic acetylcholine receptor α6 subunit confers high-level resistance to spinosad in Plutella xylostella

    PubMed Central

    Wang, Jing; Wang, Xingliang; Lansdell, Stuart J.; Zhang, Jianheng; Millar, Neil S.; Wu, Yidong

    2016-01-01

    Spinosad is a macrocyclic lactone insecticide that acts primarily at the nicotinic acetylcholine receptors (nAChRs) of target insects. Here we describe evidence that high levels of resistance to spinosad in the diamondback moth (Plutella xylostella) are associated with a three amino acid (3-aa) deletion in the fourth transmembrane domain (TM4) of the nAChR α6 subunit (Pxα6). Following laboratory selection with spinosad, the SZ-SpinR strain of P. xylostella exhibited 940-fold resistance to spinosad. In addition, the selected insect population had 1060-fold cross-resistance to spinetoram but, in contrast, no cross-resistance to abamectin was observed. Genetic analysis indicates that spinosad resistance in SZ-SpinR is inherited as a recessive and autosomal trait, and that the 3-aa deletion (IIA) in TM4 of Pxα6 is tightly linked to spinosad resistance. Because of well-established difficulties in functional expression of cloned insect nAChRs, the analogous resistance-associated deletion mutation was introduced into a prototype nAChR (the cloned human α7 subunit). Two-electrode voltage-clamp recording with wild-type and mutated nAChRs expressed in Xenopus laevis oocytes indicated that the mutation causes a complete loss of agonist activation. In addition, radioligand binding studies indicated that the 3-aa deletion resulted in significantly lower-affinity binding of the extracellular neurotransmitter-binding site. These findings are consistent with the 3-amino acid (IIA) deletion within the transmembrane domain of Pxα6 being responsible for target-site resistance to spinosad in the SZ-SpinR strain of P. xylostella. PMID:26855198

  4. NMR-Based Metabolic Profiling of Field-Grown Leaves from Sugar Beet Plants Harbouring Different Levels of Resistance to Cercospora Leaf Spot Disease

    PubMed Central

    Sekiyama, Yasuyo; Okazaki, Kazuyuki; Kikuchi, Jun; Ikeda, Seishi

    2017-01-01

    Cercospora leaf spot (CLS) is one of the most serious leaf diseases for sugar beet (Beta vulgaris L.) worldwide. The breeding of sugar beet cultivars with both high CLS resistance and high yield is a major challenge for breeders. In this study, we report the nuclear magnetic resonance (NMR)-based metabolic profiling of field-grown leaves for a subset of sugar beet genotypes harbouring different levels of CLS resistance. Leaves were collected from 12 sugar beet genotypes at four time points: seedling, early growth, root enlargement, and disease development stages. 1H-NMR spectra of foliar metabolites soluble in a deuterium-oxide (D2O)-based buffer were acquired and subjected to multivariate analyses. A principal component analysis (PCA) of the NMR data from the sugar beet leaves shows clear differences among the growth stages. At the later time points, the sugar and glycine betaine contents were increased, whereas the choline content was decreased. The relationship between the foliar metabolite profiles and resistance level to CLS was examined by combining partial least squares projection to latent structure (PLS) or orthogonal PLS (OPLS) analysis and univariate analyses. It was difficult to build a robust model for predicting precisely the disease severity indices (DSIs) of each genotype; however, GABA and Gln differentiated susceptible genotypes (genotypes with weak resistance) from resistant genotypes (genotypes with resistance greater than a moderate level) before inoculation tests. The results suggested that breeders might exclude susceptible genotypes from breeding programs based on foliar metabolites profiled without inoculation tests, which require an enormous amount of time and effort. PMID:28134762

  5. The roles of CYP6AY1 and CYP6ER1 in imidacloprid resistance in the brown planthopper: Expression levels and detoxification efficiency.

    PubMed

    Bao, Haibo; Gao, Hongli; Zhang, Yixi; Fan, Dongzhe; Fang, Jichao; Liu, Zewen

    2016-05-01

    Two P450 monooxygenase genes, CYP6AY1 and CYP6ER1, were reported to contribute importantly to imidacloprid resistance in the brown planthopper, Nilaparvata lugens. Although recombinant CYP6AY1 could metabolize imidacloprid efficiently, the expression levels of CYP6ER1 gene were higher in most resistant populations. In the present study, three field populations were collected from different countries, and the bioassay, RNAi and imidacloprid metabolism were performed to evaluate the importance of two P450s in imidacloprid resistance. All three populations, DOT (Dongtai) from China, CNA (Chainat) from Thailand and HCM (Ho Chi Minh) from Vietnam, showed high resistance to imidacloprid (57.0-, 102.9- and 89.0-fold). CYP6AY1 and CYP6ER1 were both over expressed in three populations, with highest ratio of 13.2-fold for CYP6ER1 in HCM population. Synergism test and RNAi analysis confirmed the roles of both P450 genes in imidacloprid resistance. However, CYP6AY1 was indicated more important in CNA population, and CYP6AY1 and CYP6ER1 were equal in HCM population, although the expression level of CYP6ER1 (13.2-fold) was much higher than that of CYP6AY1 (4.11-fold) in HCM population. Although the recombinant proteins of both P450 genes could metabolize imidacloprid efficiently, the catalytic activity of CYP6AY1 (Kcat=3.627 pmol/min/pmol P450) was significantly higher than that of CYP6ER1 (Kcat=2.785 pmol/min/pmol P450). It was supposed that both P450 proteins were important for imidacloprid resistance, in which CYP6AY1 metabolized imidacloprid more efficiently and CYP6ER1 gene could be regulated by imidacloprid to a higher level.

  6. Farm level risk factors for fluoroquinolone resistance in E. coli and thermophilic Campylobacter spp. on poultry farms.

    PubMed

    Taylor, N M; Wales, A D; Ridley, A M; Davies, R H

    2016-10-01

    Data on husbandry practices, performance, disease and drug use were collected during a cross-sectional survey of 89 poultry meat farms in England and Wales to provide information on possible risk factors for the occurrence of fluoroquinolone (FQ)-resistant bacteria. Faeces samples were used to classify farms as "affected" or "not affected" by FQ-resistant (FQr) Escherichia coli or Campylobacter spp. Risk factor analysis identified the use of FQ on the farms as having by far the strongest association, among the factors considered, with the occurrence of FQr bacteria. Resistant E. coli and/or Campylobacter spp. were found on 86% of the farms with a history of FQ use. However, a substantial proportion of farms with no history of FQ use also yielded FQr organisms, suggesting that resistant bacteria may transfer between farms. Further analysis suggested that for Campylobacter spp., on-farm hygiene, cleaning and disinfection between batches of birds and wildlife control were of most significance. By contrast, for E. coli biosecurity from external contamination was of particular importance, although the modelling indicated that other factors were likely to be involved. Detailed studies on a small number of sites showed that FQr E. coli can survive routine cleaning and disinfection. It appears difficult to avoid the occurrence of resistant bacteria when FQ are used on a farm, but the present findings provide evidence to support recommendations to reduce the substantial risk of the incidental acquisition of such resistance by farms where FQ are not used.

  7. Plasma levels of mature brain-derived neurotrophic factor (BDNF) and matrix metalloproteinase-9 (MMP-9) in treatment-resistant schizophrenia treated with clozapine.

    PubMed

    Yamamori, Hidenaga; Hashimoto, Ryota; Ishima, Tamaki; Kishi, Fukuko; Yasuda, Yuka; Ohi, Kazutaka; Fujimoto, Michiko; Umeda-Yano, Satomi; Ito, Akira; Hashimoto, Kenji; Takeda, Masatoshi

    2013-11-27

    Brain-derived neurotrophic factor (BDNF) regulates the survival and growth of neurons, and influences synaptic efficiency and plasticity. Peripheral BDNF levels in patients with schizophrenia have been widely reported in the literature. However, it is still controversial whether peripheral levels of BDNF are altered in patients with schizophrenia. The peripheral BDNF levels previously reported in patients with schizophrenia were total BDNF (proBDNF and mature BDNF) as it was unable to specifically measure mature BDNF due to limited BDNF antibody specificity. In this study, we examined whether peripheral levels of mature BDNF were altered in patients with treatment-resistant schizophrenia. Matrix metalloproteinase-9 (MMP-9) levels were also measured, as MMP-9 plays a role in the conversion of proBDNF to mature BDNF. Twenty-two patients with treatment-resistant schizophrenia treated with clozapine and 22 age- and sex-matched healthy controls were enrolled. The plasma levels of mature BDNF and MMP-9 were measured using ELISA kits. No significant difference was observed for mature BDNF however, MMP-9 was significantly increased in patients with schizophrenia. The significant correlation was observed between mature BDNF and MMP-9 plasma levels. Neither mature BDNF nor MMP-9 plasma levels were associated clinical variables. Our results do not support the view that peripheral BDNF levels are associated with schizophrenia. MMP-9 may play a role in the pathophysiology of schizophrenia and serve as a biomarker for schizophrenia.

  8. Fitness Costs and Stability of a High-Level Ciprofloxacin Resistance Phenotype in Salmonella enterica Serotype Enteritidis: Reduced Infectivity Associated with Decreased Expression of Salmonella Pathogenicity Island 1 Genes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The fitness costs associated with high-level fluoroquinolone resistance were examined in phenotypically and genotypically characterized ciprofloxacin-resistant Salmonella Enteritidis mutants (104-cip and 5408-cip, MIC > 32 µg/ml). The stability of the fluoroquinolone resistance phenotype in both mut...

  9. Adropin and irisin levels in relation to nutrition, body composition, and insulin resistance in patients with end-stage renal disease on chronic hemodialysis and peritoneal dialysis.

    PubMed

    Kałużna, Małgorzata; Hoppe, Krzysztof; Schwermer, Krzysztof; Ibrahim, Aisha Y; Pawlaczyk, Krzysztof; Ziemnicka, Katarzyna

    2016-07-25

    INTRODUCTION    Newly discovered myokines, adropin, and irisin, are regulators of energy homeostasis and metabolism in humans. In end-stage renal disease (ESRD), the significance and role of irisin and adropin as metabolism regulators are still unclear. OBJECTIVES    The aim of this study was to evaluate serum adropin and irisin levels and establish their relation to insulin resistance, nutritional status, and hydration status in patients on chronic hemodialysis (HD) and on peritoneal dialysis (PD). PATIENTS AND METHODS    The study consisted of 71 subjects, including 48 patients (18 women, 30 men; median age, 56.5 years; range, 26-84 years) either on HD (n = 41) or PD (n = 7) and 36 healthy controls matched for age and sex. We measured the serum levels of adropin, irisin, creatinine, albumin, glucose, and insulin, as well as the plasma levels of lipids. The bioimpedance method was used to evaluate the body composition and overhydration in patients with ESRD. RESULTS    Irisin levels were significantly lower in patients with ESRD compared with controls, but there were no differences in adropin levels between both study groups. Adropin levels were inversely correlated with body mass, lean tissue mass, total, intracellular, and extracellular water, and albumin concentrations in patients with ESRD. Irisin levels were positively correlated with glucose levels and homeostasis model assessment of insulin resistance. No significant correlations were observed between adropin and irisin concentrations and overhydration. CONCLUSIONS    Adropin may be considered as a new marker of nutritional status in patients with ESRD. The significance and cause of low irisin levels characteristic for these patients are still unclear. Adropin and irisin should be further investigated as possible markers of cachexia and insulin resistance in patients with ESRD.

  10. Analysis and design of tunable wideband microwave photonics phase shifter based on Fabry-Perot cavity and Bragg mirrors in silicon-on-insulator waveguide.

    PubMed

    Qu, Pengfei; Zhou, Jingran; Chen, Weiyou; Li, Fumin; Li, Haibin; Liu, Caixia; Ruan, Shengping; Dong, Wei

    2010-04-20

    We designed a microwave (MW) photonics phase shifter, consisting of a Fabry-Perot filter, a phase modulation region (PMR), and distributed Bragg reflectors, in a silicon-on-insulator rib waveguide. The thermo-optics effect was employed to tune the PMR. It was theoretically demonstrated that the linear MW phase shift of 0-2pi could be achieved by a refractive index variation of 0-9.68x10(-3) in an ultrawideband (about 38?GHz-1.9?THz), and the corresponding tuning resolution was about 6.92 degrees / degrees C. The device had a very compact size. It could be easily integrated in silicon optoelectronic chips and expected to be widely used in the high-frequency MW photonics field.

  11. Thin Film Ba(x)Sr(1-x)TiO3 Ku- and K-Band Phase Shifters Grown on MgO Substrates

    NASA Technical Reports Server (NTRS)

    VanKeuls, F. W.; Mueller, C. H.; Miranda, F. A.; Romanofsky, R. R.; Horwitz, J. S.; Chang, W.; Kim, W. J.

    1999-01-01

    We report measurements of gold circuits fabricated on four Ba(x)Sr(1-x)TiO3 films doped with 1% Mn grown on MgO substrates by laser ablation. Low frequency measurements of epsilon(sub r) and tan(delta) on interdigital capacitors are compared with high frequency measurements of phase shift and insertion loss on coupled microstrip phase shifters done on the same films. The variation in temperature of both high and low frequency device parameters is compared. Annealed and unannealed films are compared. Room temperature figures of merit of phase shift per insertion loss of up to 58.4 C/dB at 18 GHz and 400 V dc bias were measured.

  12. High MET amplification level as a resistance mechanism to osimertinib (AZD9291) in a patient that symptomatically responded to crizotinib treatment post-osimertinib progression.

    PubMed

    Ou, Sai-Hong Ignatius; Agarwal, Nikita; Ali, Siraj M

    2016-08-01

    Third-generation EGFR TKI has been approved in the US and EU for the treatment of EGFR mutant T790M+ NSCLC patients that are resistant to first- or second generation EGFR TKIs. Here we report a patient who developed resistance to osimertinib after a confirmed partial response for 9 months. Pre-osimertinib and post-osimertinib tumor biopsy revealed the emergence of high level of MET amplification (30 copies) post osimertinib treatment. Patient was treated with single agent crizotinib, a known MET inhibitor, with transient symptomatic benefit. MET amplification is one potential resistance mechanism to osimertinib and combination of osimertinib and a MET inhibitor should be investigated post-osimertinib progression in EGFR mutant T790M+ NSCLC patients whose harbored acquired MET amplification.

  13. MDR-TB treatment as prevention: The projected population-level impact of expanded treatment for multidrug-resistant tuberculosis

    PubMed Central

    Azman, Andrew S.; Cobelens, Frank G.; Dowdy, David W.

    2017-01-01

    Background In 2013, approximately 480,000 people developed active multidrug-resistant tuberculosis (MDR-TB), while only 97,000 started MDR-TB treatment. We sought to estimate the impact of improving access to MDR-TB diagnosis and treatment, under multiple diagnostic algorithm and treatment regimen scenarios, on ten-year projections of MDR-TB incidence and mortality. Methods We constructed a dynamic transmission model of an MDR-TB epidemic in an illustrative East/Southeast Asian setting. Using approximate Bayesian computation, we investigated a wide array of potential epidemic trajectories consistent with current notification data and known TB epidemiology. Results Despite an overall projected decline in TB incidence, data-consistent simulations suggested that MDR-TB incidence is likely to rise between 2015 and 2025 under continued 2013 treatment practices, although with considerable uncertainty (median 17% increase, 95% Uncertainty Range [UR] -38% to +137%). But if, by 2017, all identified active TB patients with previously-treated TB could be tested for drug susceptibility, and 85% of those with MDR-TB could initiate MDR-appropriate treatment, then MDR-TB incidence in 2025 could be reduced by 26% (95% UR 4–52%) relative to projections under continued current practice. Also expanding this drug-susceptibility testing and appropriate MDR-TB treatment to treatment-naïve as well as previously-treated TB cases, by 2020, could reduce MDR-TB incidence in 2025 by 29% (95% UR 6–55%) compared to continued current practice. If this diagnosis and treatment of all MDR-TB in known active TB cases by 2020 could be implemented via a novel second-line regimen with similar effectiveness and tolerability as current first-line therapy, a 54% (95% UR 20–74%) reduction in MDR-TB incidence compared to current-practice projections could be achieved by 2025. Conclusions Expansion of diagnosis and treatment of MDR-TB, even using current sub-optimal second-line regimens, is expected

  14. Porin alterations present in non-carbapenemase-producing Enterobacteriaceae with high and intermediate levels of carbapenem resistance in Chile.

    PubMed

    Wozniak, Aniela; Villagra, Nicolás A; Undabarrena, Agustina; Gallardo, Natalia; Keller, Nicole; Moraga, Marcela; Román, Juan C; Mora, Guido C; García, Patricia

    2012-09-01

    The main goal of this work was to identify the mechanisms responsible for carbapenem resistance in 61 Chilean clinical isolates of Enterobacteriaceae (Enterobacter spp., Serratia marcescens, Morganella morganii, Escherichia coli and Klebsiella pneumoniae) with reduced susceptibility to at least one carbapenem (ertapenem, imipenem or meropenem). All of the isolates were analysed for the presence of carbapenemases, extended spectrum β-lactamases (ESBLs), AmpC enzymes and outer-membrane proteins. None of the isolates exhibited carbapenemase activity nor did they have any of the carbapenemase genes that were screened for. Most of the 61 strains produced at least one ESBL and/or one AmpC enzyme and either lost their porins or had altered porins according to sequence analysis. The distribution of ESBLs and AmpC enzymes was different among the species studied. Resistance in K. pneumoniae and E. coli isolates was associated with ESBLs; in M. morganii isolates, resistance was attributed to overexpression of an AmpC enzyme; and in Enterobacter spp. isolates, resistance was associated with both types of enzymes. In K. pneumoniae isolates, porin integrity was more a determinant of carbapenem resistance than the presence of ESBLs, whereas in isolates of Enterobacter spp., M. morganii and S. marcescens, the presence of an overexpressed AmpC enzyme was associated with higher imipenem and meropenem MIC values. Therefore, carbapenem resistance in Chilean isolates is not due to true carbapenemases but rather to a combination of porin loss/alteration and β-lactamase activity. The fact that carbapenemases were not detected in this study is unique, given that many countries in the region have already reported the presence of these enzymes.

  15. Selective advantage of resistant strains at trace levels of antibiotics: a simple and ultrasensitive color test for detection of antibiotics and genotoxic agents.

    PubMed

    Liu, Anne; Fong, Amie; Becket, Elinne; Yuan, Jessica; Tamae, Cindy; Medrano, Leah; Maiz, Maria; Wahba, Christine; Lee, Catherine; Lee, Kim; Tran, Katherine P; Yang, Hanjing; Hoffman, Robert M; Salih, Anya; Miller, Jeffrey H

    2011-03-01

    Many studies have examined the evolution of bacterial mutants that are resistant to specific antibiotics, and many of these focus on concentrations at and above the MIC. Here we ask for the minimum concentration at which existing resistant mutants can outgrow sensitive wild-type strains in competition experiments at antibiotic levels significantly below the MIC, and we define a minimum selective concentration (MSC) in Escherichia coli for two antibiotics, which is near 1/5 of the MIC for ciprofloxacin and 1/20 of the MIC for tetracycline. Because of the prevalence of resistant mutants already in the human microbiome, allowable levels of antibiotics to which we are exposed should be below the MSC. Since this concentration often corresponds to low or trace levels of antibiotics, it is helpful to have simple tests to detect such trace levels. We describe a simple ultrasensitive test for detecting the presence of antibiotics and genotoxic agents. The test is based on the use of chromogenic proteins as color markers and the use of single and multiple mutants of Escherichia coli that have greatly increased sensitivity to either a wide range of antibiotics or specific antibiotics, antibiotic families, and genotoxic agents. This test can detect ciprofloxacin at 1/75 of the MIC.

  16. Field Level RNAi-Mediated Resistance to Cassava Brown Streak Disease across Multiple Cropping Cycles and Diverse East African Agro-Ecological Locations

    PubMed Central

    Wagaba, Henry; Beyene, Getu; Aleu, Jude; Odipio, John; Okao-Okuja, Geoffrey; Chauhan, Raj Deepika; Munga, Theresia; Obiero, Hannington; Halsey, Mark E.; Ilyas, Muhammad; Raymond, Peter; Bua, Anton; Taylor, Nigel J.; Miano, Douglas; Alicai, Titus

    2017-01-01

    Cassava brown streak disease (CBSD) presents a serious threat to cassava production in East and Central Africa. Currently, no cultivars with high levels of resistance to CBSD are available to farmers. Transgenic RNAi technology was employed to combat CBSD by fusing coat protein (CP) sequences from Ugandan cassava brown streak virus (UCBSV) and Cassava brown streak virus (CBSV) to create an inverted repeat construct (p5001) driven by the constitutive Cassava vein mosaic virus promoter. Twenty-five plant lines of cultivar TME 204 expressing varying levels of small interfering RNAs (siRNAs) were established in confined field trials (CFTs) in Uganda and Kenya. Within an initial CFT at Namulonge, Uganda, non-transgenic TME 204 plants developed foliar and storage root CBSD incidences at 96–100% by 12 months after planting. In contrast, 16 of the 25 p5001 transgenic lines showed no foliar symptoms and had less than 8% of their storage roots symptomatic for CBSD. A direct positive correlation was seen between levels of resistance to CBSD and expression of transgenic CP-derived siRNAs. A subsequent CFT was established at Namulonge using stem cuttings from the initial trial. All transgenic lines established remained asymptomatic for CBSD, while 98% of the non-transgenic TME 204 stake-derived plants developed storage roots symptomatic for CBSD. Similarly, very high levels of resistance to CBSD were demonstrated by TME 204 p5001 RNAi lines grown within a CFT over a full cropping cycle at Mtwapa, coastal Kenya. Sequence analysis of CBSD causal viruses present at the trial sites showed that the transgenic lines were exposed to both CBSV and UCBSV, and that the sequenced isolates shared >90% CP identity with transgenic CP sequences expressed by the p5001 inverted repeat expression cassette. These results demonstrate very high levels of field resistance to CBSD conferred by the p5001 RNAi construct at diverse agro-ecological locations, and across the vegetative cropping cycle

  17. Usefulness of plasma HGF level for monitoring acquired resistance to EGFR tyrosine kinase inhibitors in non-small cell lung cancer.

    PubMed

    Umeguchi, Hitomi; Sueoka-Aragane, Naoko; Kobayashi, Naomi; Nakamura, Tomomi; Sato, Akemi; Takeda, Yuji; Hayashi, Shinichiro; Sueoka, Eisaburo; Kimura, Shinya

    2015-01-01

    Monitoring of molecular markers is indispensable for deciding subsequent treatment after acquired resistance to molecular-targeted therapy. According to results using re-biopsy, EGFR T790M mutation and overexpression of hepatocyte growth factor (HGF) are major mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). The aim of the present study was to assess whether quantification of HGF using peripheral blood in addition to detection of T790M with plasma DNA is useful for monitoring as an alternative to invasive re-biopsy. HGF levels in plasma were determined using ELISA and T790M mutation was detected using mutation-biased PCR and quenched probe system (MBP-QP). The median level of HGF in plasma at baseline was 140 pg/ml and was significantly higher in the advanced stage of cancer and in smokers and predicted poor survival as determined using 315 plasma samples from 225 lung cancer patients. T790M was detected with plasma DNA in 9 of 16 patients who acquired resistance to EGFR-TKIs and a greater than 1.5-fold elevation compared with pretreatment HGF levels was observed in 6 patients after acquired resistance. Eleven of 16 patients (69%) showed either HGF elevation or T790M in plasma samples, with both outcomes observed in 25% of patients; this is consistent with results based on re-biopsy reported from other laboratories. Considering these results, assessing HGF and T790M using peripheral blood could be useful for monitoring mechanisms of acquired resistance to EGFR-TKIs.

  18. Fasciola hepatica demonstrates high levels of genetic diversity, a lack of population structure and high gene flow: possible implications for drug resistance.

    PubMed

    Beesley, Nicola J; Williams, Diana J L; Paterson, Steve; Hodgkinson, Jane

    2017-01-01

    Fasciola hepatica, the liver fluke, is a trematode parasite of considerable economic importance to the livestock industry and is a re-emerging zoonosis that poses a risk to human health in F. hepatica-endemic areas worldwide. Drug resistance is a substantial threat to the current and future control of F. hepatica, yet little is known about how the biology of the parasite influences the development and spread of resistance. Given that F. hepatica can self-fertilise and therefore inbreed, there is the potential for greater population differentiation and an increased likelihood of recessive alleles, such as drug resistance genes, coming together. This could be compounded by clonal expansion within the snail intermediate host and aggregation of parasites of the same genotype on pasture. Alternatively, widespread movement of animals that typically occurs in the UK could promote high levels of gene flow and prevent population differentiation. We identified clonal parasites with identical multilocus genotypes in 61% of hosts. Despite this, 84% of 1579 adult parasites had unique multilocus genotypes, which supports high levels of genotypic diversity within F. hepatica populations. Our analyses indicate a selfing rate no greater than 2%, suggesting that this diversity is in part due to the propensity for F. hepatica to cross-fertilise. Finally, although we identified high genetic diversity within a given host, there was little evidence for differentiation between populations from different hosts, indicating a single panmictic population. This implies that, once those emerge, anthelmintic resistance genes have the potential to spread rapidly through liver fluke populations.

  19. Grapevine rootstock effects on scion sap phenolic levels, resistance to Xylella fastidiosa infection, and progression of Pierce’s disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The xylem-limited bacterium Xylella fastidiosa (Xf) causes Pierce’s disease (PD), an important disease of grapevine, Vitis vinifera L. Grapevine rootstocks were developed to provide increased resistance to root disease, but rootstock effects on cane and vine diseases remain unclear. Grapevines that ...

  20. High-level quinolone resistance is associated with the overexpression of smeVWX in Stenotrophomonas maltophilia clinical isolates.

    PubMed

    García-León, G; Ruiz de Alegría Puig, C; García de la Fuente, C; Martínez-Martínez, L; Martínez, J L; Sánchez, M B

    2015-05-01

    Stenotrophomonas maltophilia is the only known bacterium in which quinolone-resistant isolates do not present mutations in the genes encoding bacterial topoisomerases. The expression of the intrinsic quinolone resistance elements smeDEF, smeVWX and Smqnr was analysed in 31 clinical S. maltophilia isolates presenting a minimum inhibitory concentration (MIC) range to ciprofloxacin between 0.5 and > 32 μg/mL; 11 (35.5%) overexpressed smeDEF, 2 (6.5%) presenting the highest quinolone MICs overexpressed smeVWX and 1 (3.2%) overexpressed Smqnr. Both strains overexpressing smeVWX presented changes at the Gly266 position of SmeRv, the repressor of smeVWX. Changes at the same position were previously observed in in vitro selected S. maltophilia quinolone-resistant mutants, indicating this amino acid is highly relevant for the activity of SmeRv in repressing smeVWX expression. For the first time SmeVWX overexpression is associated with quinolone resistance of S. maltophilia clinical isolates.

  1. Plants on constant alert: elevated levels of jasmonic acid and jasmonate-induced transcripts in caterpillar resistant maize

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plant defense responses against insect herbivores frequently depend on the biosynthesis and action of jasmonic acid (JA) and its conjugates. To better understand JA signaling pathways in maize (Zea mays L.), we have examined two maize genotypes, Mp708 and Tx601. Mp708 is resistant to feeding by le...

  2. Identification of tolerance to Fusarium root rot in wild pea germplasm with high levels of partial resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fusarium root rot, caused by Fusarium solani f. sp. pisi, is a serious root rot pathogen affecting peas in all pea growing areas of the USA and is damaging in both dryland and irrigated pea fields. Partial resistance to Fusarium root rot in 44 accessions from the Pisum Core Collection located in Pu...

  3. On the relation between deep level compensation, resistivity and electric field in semi-insulating CdTe:Cl radiation detectors

    NASA Astrophysics Data System (ADS)

    Cola, Adriano; Farella, Isabella; Pousset, Jeremy; Valletta, Antonio

    2016-12-01

    A compensation model for semi-insulating CdTe:Cl based on a single dominant deep level 0.725 eV above the valence band is proposed. The model is corroborated by experimental evidence: resistivity measurements as a function of temperature on bulk crystals and stationary electric field distributions in Ohmic/Schottky radiation detectors, obtained by the Pockels effect. The latter are in close agreement with the numerical solutions of transport equations when considering the deep centre concentration in the range 2 - 4 × 1012 cm-3, and a compensation ratio R = 2.1, this one being consistent with an original ambipolar analysis of resistivity. More generally, the approach elucidates the role of electrical contacts and deep levels in controlling the electric fields in devices based on compensated materials.

  4. Chronic exposure to triclosan sustains microbial community shifts and alters antibiotic resistance gene levels in anaerobic digesters.

    PubMed

    Carey, Daniel E; Zitomer, Daniel H; Kappell, Anthony D; Choi, Melinda J; Hristova, Krassimira R; McNamara, Patrick J

    2016-08-10

    Triclosan, an antimicrobial chemical found in consumer personal care products, has been shown to stimulate antibiotic resistance in pathogenic bacteria. Although many studies focus on antibiotic resistance pertinent to medical scenarios, resistance developed in natural and engineered environments is less studied and has become an emerging concern for human health. In this study, the impacts of chronic triclosan (TCS) exposure on antibiotic resistance genes (ARGs) and microbial community structure were assessed in lab-scale anaerobic digesters. TCS concentrations from below detection to 2500 mg kg(-1) dry solids were amended into anaerobic digesters over 110 days and acclimated for >3 solid retention time values. Four steady state TCS concentrations were chosen (30-2500 mg kg(-1)). Relative abundance of mexB, a gene coding for a component of a multidrug efflux pump, was significantly higher in all TCS-amended digesters (30 mg kg(-1) or higher) relative to the control. TCS selected for bacteria carrying tet(L) and against those carrying erm(F) at concentrations which inhibited digester function; the pH decrease associated with digester failure was suspected to cause this selection. Little to no impact of TCS was observed on intI1 relative abundance. Microbial communities were also surveyed by high-throughput 16S rRNA gene sequencing. Compared to the control digesters, significant shifts in community structure towards clades containing commensal and pathogenic bacteria were observed in digesters containing TCS. Based on these results, TCS should be included in studies and risk assessments that attempt to elucidate relationships between chemical stressors (e.g. antibiotics), antibiotic resistance genes, and public health.

  5. Impact of the postpump resistance on pressure-flow waveform and hemodynamic energy level in a neonatal pulsatile centrifugal pump.

    PubMed

    Wang, Shigang; Haines, Nikkole; Richardson, J Scott; Dasse, Kurt A; Undar, Akif

    2009-01-01

    This study tested the impact of different postpump resistances on pulsatile pressure-flow waveforms and hemodynamic energy output in a mock extracorporeal system. The circuit was primed with a 40% glycerin-water mixture, and a PediVAS centrifugal pump was used. The pre- and postpump pressures and flow rates were monitored via a data acquisition system. The postpump resistance was adjusted using a Hoffman clamp at the outlet of the pump. Five different postpump resistances and rotational speeds were tested with nonpulsatile (NP: 5000 RPM) and pulsatile (P: 4000 RPM) modes. No backflow was found when using pulsatile flow. With isoresistance, increased arterial resistances decreased pump flow rates (NP: from 1,912 ml/min to 373 ml/min; P: from 1,485 ml/min to 288 ml/min), increased postpump pressures (NP: from 333 mm Hg to 402 mm Hg; P: from 223 mm Hg to 274 mm Hg), and increased hemodynamic energy output with pulsatile mode. Pump flow rate correlated linearly with rotational speed (RPMs) of the pump, whereas postpump pressures and hemodynamic energy outputs showed curvilinear relationships with RPMs. The maximal pump flow rate also increased from 618 ml/min to 4,293 ml/min with pulsatile mode and from 581 ml/min to 5,665 ml/min with nonpulsatile mode. Results showed that higher postpump resistance reduced the pump flow range, and increased postpump pressure and surplus hemodynamic energy output with pulsatile mode. Higher rotational speeds also generated higher pump flow rates, postpump pressures, and increased pulsatility.

  6. Combination Patterns of Major R Genes Determine the Level of Resistance to the M. oryzae in Rice (Oryza sativa L.).

    PubMed

    Wu, Yunyu; Xiao, Ning; Yu, Ling; Pan, Cunhong; Li, Yuhong; Zhang, Xiaoxiang; Liu, Guangqing; Dai, Zhengyuan; Pan, Xuebiao; Li, Aihong

    2015-01-01

    Rice blast caused by Magnaporthe oryzae is the most devastating disease of rice and poses a serious threat to world food security. In this study, the distribution and effectiveness of 18 R genes in 277 accessions were investigated based on pathogenicity assays and molecular markers. The results showed that most of the accessions exhibited some degree of resistance (resistance frequency, RF >50%). Accordingly, most of the accessions were observed to harbor two or more R genes, and the number of R genes harbored in accessions was significantly positively correlated with RF. Some R genes were demonstrated to be specifically distributed in the genomes of rice sub-species, such as Pigm, Pi9, Pi5 and Pi1, which were only detected in indica-type accessions, and Pik and Piz, which were just harbored in japonica-type accessions. By analyzing the relationship between R genes and RF using a multiple stepwise regression model, the R genes Pid3, Pi5, Pi9, Pi54, Pigm and Pit were found to show the main effects against M. oryzae in indica-type accessions, while Pita, Pb1, Pik, Pizt and Pia were indicated to exhibit the main effects against M. oryzae in japonica-type accessions. Principal component analysis (PCA) and cluster analysis revealed that combination patterns of major R genes were the main factors determining the resistance of rice varieties to M. oryzae, such as 'Pi9+Pi54', 'Pid3+Pigm', 'Pi5+Pid3+Pigm', 'Pi5+Pi54+Pid3+Pigm', 'Pi5+Pid3' and 'Pi5+Pit+Pid3' in indica-type accessions and 'Pik+Pib', 'Pik+Pita', 'Pik+Pb1', 'Pizt+Pia' and 'Pizt+Pita' in japonica-type accessions, which were able to confer effective resistance against M. oryzae. The above results provide good theoretical support for the rational utilization of combinations of major R genes in developing rice cultivars with broad-spectrum resistance.

  7. Studies of deep levels in high resistivity silicon detectors irradiated by high fluence fast neutrons using a thermally stimulated current spectrometer

    SciTech Connect

    Li, Z.; Kraner, H.W.; Chen, W.; Beuttenmuller, R.; Biggeri, U.; Bruzzi, M.; Borchi, E.; Baldini, A.; Spillantini, P. |

    1993-04-01

    Measurements of deep level spectrum of high resistivity silicon detectors irradiated by high fluence fast neutrons ({Phi}{sub n}: 2 {times} 10{sup 12}n/cm{sup 2}) have been made using a thermally stimulated current (TSC) spectrometer. It has been found that at least nine new defect levels, with peaking temperature of 19K, 27K, 36K, 44K, 49K, 83K, 93K, 105K, and 120K, begin to appear when {Phi}{sub n} {ge} 1 {times} 10{sup 13}n/cm. All peaks have strong dependences on the filling voltage (V{sub fill}, forward bias) or injection current especially for high fluence ({Phi}{sub n} {ge} 10{sup 13} n/cm{sup 2}) situations. The defect concentration, energy level in the band gap, and cross section of each deep level, totaling, at least 13, have been studied systematically and possible identifications of the levels have been discussed.

  8. Community Analysis of Root- and Tuber-Associated Bacteria in Field-Grown Potato Plants Harboring Different Resistance Levels against Common Scab

    PubMed Central

    Kobayashi, Akira; Kobayashi, Yuki Ohdaira; Someya, Nobutaka; Ikeda, Seishi

    2015-01-01

    Eight genotypes of potato plants with different resistance levels against common scab were grown in a field infested with Streptomyces turgidiscabies. DNA was extracted from the roots, tubers, and rhizosphere soils of each of the eight genotypes at the flowering stage, and the quantity of S. turgidiscabies genomic DNA was assessed by real-time PCR using a TaqMan probe. The results obtained showed that the different potato genotypes had significant impacts on the population levels of S. turgidiscabies between resistant and susceptible genotypes in the tubers, but not in the roots or rhizosphere soils. Clone analyses of 16S rRNA gene libraries from the eight potato genotypes identified three phyla (Proteobacteria, Firmicutes, and Actinobacteria) as dominant taxa in root and tuber clone libraries, while a clustering analysis identified 391 operational taxonomic units (OTUs) at the species level. Eleven OTUs closely related to Aquicella siphonis, Arthrobacter nicotinovorans, Streptomyces rishiriensis, Rhodococcus baikonurensis, Rhizobium radiobacter, Rhizobium etli, Phyllobacterium myrsinacearum, Paenibacillus pabuli, Paenibacillus alginolyticus, and Bacillus halmapalus were detected in the root or tuber libraries of all the potato genotypes examined. Furthermore, an abundance of OTUs related to Aquicella and Rhodococcus was observed in the rhizospheres of resistant and susceptible potato genotypes, respectively. Based on this ecological information, an efficient survey may be conducted for biological agents from the potato rhizosphere. PMID:26657303

  9. Associations of Haplotypes Upstream of IRS1 with Insulin Resistance, Type 2 Diabetes, Dyslipidemia, Preclinical Atherosclerosis, and Skeletal Muscle LOC646736 mRNA Levels

    PubMed Central

    Soyal, Selma M.; Felder, Thomas; Auer, Simon; Oberkofler, Hannes; Iglseder, Bernhard; Paulweber, Bernhard; Dossena, Silvia; Nofziger, Charity; Paulmichl, Markus; Esterbauer, Harald; Krempler, Franz; Patsch, Wolfgang

    2015-01-01

    The genomic region ~500 kb upstream of IRS1 has been implicated in insulin resistance, type 2 diabetes, adverse lipid profile, and cardiovascular risk. To gain further insight into this chromosomal region, we typed four SNPs in a cross-sectional cohort and subjects with type 2 diabetes recruited from the same geographic region. From 16 possible haplotypes, 6 haplotypes with frequencies >0.01 were observed. We identified one haplotype that was protective against insulin resistance (determined by HOMA-IR and fasting plasma insulin levels), type 2 diabetes, an adverse lipid profile, increased C-reactive protein, and asymptomatic atherosclerotic disease (assessed by intima media thickness of the common carotid arteries). BMI and total adipose tissue mass as well as visceral and subcutaneous adipose tissue mass did not differ between the reference and protective haplotypes. In 92 subjects, we observed an association of the protective haplotype with higher skeletal muscle mRNA levels of LOC646736, which is located in the same haplotype block as the informative SNPs and is mainly expressed in skeletal muscle, but only at very low levels in liver or adipose tissues. These data suggest a role for LOC646736 in human insulin resistance and warrant further studies on the functional effects of this locus. PMID:26090471

  10. Differential resistance of human embryonic stem cells and somatic cell types to hydrogen peroxide-induced genotoxicity may be dependent on innate basal intracellular ROS levels.

    PubMed

    Vinoth, Kumar Jayaseelan; Manikandan, Jayapal; Sethu, Swaminathan; Balakrishnan, Lakshmidevi; Heng, Alexis; Lu, Kai; Poonepalli, Anuradha; Hande, Manoor Prakash; Cao, Tong

    2015-01-01

    Previously, we demonstrated that undifferentiated human embryonic stem cells (hESC) displayed higher resistance to oxidative and genotoxic stress compared to somatic cells, but did not further probe the underlying mechanisms. Using H₂O₂-induced genotoxicity as a model, this study investigated whether higher resistance of hESC to oxidative and genotoxic stress could be due to lower innate basal intracellular levels of reactive oxygen species (ROS), as compared to their differentiated fibroblastic progenies (H1F) and two other somatic cell types - human embryonic palatal mesenchymal (HEPM) cells and peripheral blood lymphocytes (PBL). Comet assay demonstrated that undifferentiated hESC consistently sustained lower levels of DNA damage upon acute exposure to H₂O₂ for 30 min, compared to somatic cells. DCFDA and HE staining with flow cytometry showed that undifferentiated hESC had lower innate basal intracellular levels of reactive oxygen species compared to somatic cells, which could lead to their higher resistance to genotoxic stress upon acute exposure to H₂O₂.

  11. Rapid and Sensitive Oligonucleotide Ligation Assay for Detection of Mutations in Human Immunodeficiency Virus Type 1 Associated with High-Level Resistance to Protease Inhibitors

    PubMed Central

    Beck, Ingrid A.; Mahalanabis, Madhumita; Pepper, Gregory; Wright, Amy; Hamilton, Shannon; Langston, Erika; Frenkel, Lisa M.

    2002-01-01

    A sensitive, specific, and high-throughput oligonucleotide ligation assay (OLA) for the detection of genotypic human immunodeficiency virus type 1 (HIV-1) resistance to Food and Drug Administration-approved protease inhibitors was developed and evaluated. This ligation-based assay uses differentially modified oligonucleotides specific for wild-type or mutant sequences, allowing sensitive and simple detection of both genotypes in a single well of a microtiter plate. Oligonucleotides were designed to detect primary mutations associated with high-level resistance to amprenavir, nelfinavir, indinavir, ritonavir, saquinavir, and lopinavir, including amino acid substitutions D30N, I50V, V82A/S/T, I84V, N88D, and L90M. Plasma HIV-1 RNA from 54 infected patients was amplified by reverse transcription-PCR and sequenced by using dideoxynucleotide chain terminators for evaluation of mutations associated with drug resistance. These same amplicons were genotyped by the OLA at positions 30, 50, 82, 88, 84, and 90 for a total of 312 codons. The sensitivity of detection of drug-resistant genotypes was 96.7% (87 of 90 mutant codons) in the OLA compared to 92.2% (83 of 90) in consensus sequencing, presumably due to the increased sensitivity of the OLA. The OLA detected genetic subpopulations more often than sequencing, detecting 30 mixtures of mutant and wild-type sequences and two mixtures of drug-resistant sequences compared to 15 detected by DNA sequencing. Reproducible and semiquantitative detection of the mutant and the wild-type genomes by the OLA was observed by analysis of wild-type and mutant plasmid mixtures containing as little as 5% of either genotype in a background of the opposite genome. This rapid, simple, economical, and highly sensitive assay provides a practical alternative to dideoxy sequencing for genotypic evaluation of HIV-1 resistance to antiretrovirals. PMID:11923366

  12. Sensitive Oligonucleotide Ligation Assay for Low-Level Detection of Nevirapine Resistance Mutations in Human Immunodeficiency Virus Type 1 Quasispecies▿ †

    PubMed Central

    Lalonde, Matthew S.; Troyer, Ryan M.; Syed, Aslam R.; Bulime, Stanley; Demers, Korey; Bajunirwe, Francis; Arts, Eric J.

    2007-01-01

    This study has adapted the oligonucleotide ligation assay (OLA) to probe for low-level nevirapine (NVP) resistance mutations K103N and Y181C in the human immunodeficiency virus type 1 (HIV-1) population of infected mother-infant pairs from Uganda. When NVP is used to prevent perinatal transmission, NVP-resistant HIV-1 clones may be rapidly selected due to a low barrier for mutation and a relatively high level of fitness (compared to that of other drug-resistant HIV-1 clones). Monitoring for even a low frequency of NVP resistance mutations may help predict the success of subsequent treatment or warrant the use of another regimen to prevent transmission in a subsequent pregnancy. The standard OLA was optimized by using nonstandard bases in oligonucleotides to allow promiscuous base pairing and accommodate significant HIV-1 heterogeneity. Radiolabeled as opposed to fluorescently tagged oligonucleotides increased the sensitivity, whereas alteration of the template, oligonucleotides, salt, and thermostable DNA ligase concentrations increased the specificity for the detection of minority codons. This modified OLA is now capable of detecting mutants with the K103N or the Y181C mutation present in an HIV-1 population at a frequency of ∼0.4% and is at least 10- to 30-fold more sensitive than the original protocol. A cohort of 19 Ugandan mothers who received NVP treatment perinatally were sampled 6 weeks postdelivery. Ten of 19 HIV-1 DNA samples extracted from peripheral blood mononuclear cells had a detectable K103N (0.5 to 44%) or Y181C (0.8 to 92.5%) mutation, but only one plasma HIV-1 RNA sample had a viral population with the Y181C mutation. These findings suggest that OLA is a robust, sensitive, and specific method for the detection of low-frequency drug resistance mutations in an intrapatient HIV-1 population. PMID:17567789

  13. 3β-Acetyl tormentic acid reverts MRP1/ABCC1 mediated cancer resistance through modulation of intracellular levels of GSH and inhibition of GST activity.

    PubMed

    Rocha, Gleice da Graça; Oliveira, Rodrigo Rodrigues; Kaplan, Maria Auxiliadora Coelho; Gattass, Cerli Rocha

    2014-10-15

    ABC transporter overexpression is an important mechanism of multidrug resistance (MDR) and one of the main obstacles to successful cancer treatment. As these proteins actively remove chemotherapeutics from the tumor cells, the pharmacological inhibition of their activity is a possible strategy to revert drug resistance. Moreover, the ability of MDR inhibitors to sensitize resistant cells to conventional drugs is important for their clinical use. Evidence has shown that the multidrug resistance protein 1 (MRP1/ABCC1) is a negative prognostic marker in patients with lung, gastric, or breast cancers or neuroblastoma. Previous data have shown that 3β-acetyl tormentic acid (3ATA) inhibits the transport activity of the protein MRP1/ABCC1. In this study, we evaluated the ability of 3ATA to sensitize an MDR cell line (GLC4/ADR), which overexpresses MRP1, and investigated the anti-MRP1 mechanisms activated by 3ATA. The results showed that 3ATA is able to reverse the resistance of the MDR cell line to doxorubicin and vincristine, two drugs that are commonly used in cancer chemotherapy. Regarding the sensitizing mechanism induced by 3ATA, this work shows that the triterpene does not modulate the expression of MRP1/ABCC1 but is able to reduce total intracellular glutathione (GSH) levels and decrease the activity of glutathione-s-transferase (GST), the enzyme responsible for the glutathione conjugation of xenobiotics. Together, these results show that 3ATA sensitizes the MDR cell line overexpressing MRP1/ABCC1 to antineoplastic drugs and that this effect is mediated by the modulation of intracellular levels of GSH and GST activity.

  14. Effect of physical activity level on biomarkers of inflammation and insulin resistance over 5 years in outpatients with coronary heart disease (from the Heart and Soul Study).

    PubMed

    Jarvie, Jennifer L; Whooley, Mary A; Regan, Mathilda C; Sin, Nancy L; Cohen, Beth E

    2014-10-15

    Higher levels of physical activity are associated with lower rates of coronary heart disease (CHD). Previous studies have suggested that this is due partly to lower levels of inflammation and insulin resistance. The aim of this study was to determine whether physical activity level was associated with inflammation or insulin resistance during a 5-year period in outpatients with known CHD. A total of 656 participants from the Heart and Soul Study, a prospective cohort study of outpatients with documented CHD, were evaluated. Self-reported physical activity frequency was assessed at baseline and after 5 years of follow-up. Participants were classified as low versus high activity at each visit, yielding 4 physical activity groups: stable low activity, decreasing activity (high at baseline to low at year 5), increasing activity (low at baseline to high at year 5), and stable high activity. Year 5 markers of inflammation (C-reactive protein [CRP], interleukin-6, and fibrinogen) and insulin resistance (insulin, glucose, and glycated hemoglobin) were compared across the 4 activity groups. After 5 years of follow-up, higher activity was associated with lower mean levels of all biomarkers. In the fully adjusted regression models, CRP, interleukin-6, and glucose remained independently associated with physical activity frequency (log CRP, p for trend across activity groups = 0.03; log interleukin-6, p for trend = 0.01; log glucose, p for trend = 0.003). Subjects with stable high activity typically had the lowest levels of biomarkers. In conclusion, in this novel population of outpatients with known CHD followed for 5 years, higher physical activity frequency was independently associated with lower levels of CRP, interleukin-6, and glucose.

  15. Antibiotic prescribing and resistance: knowledge level of medical students of clinical years of University Sultan Zainal Abidin, Malaysia

    PubMed Central

    Haque, Mainul; Rahman, Nor Iza A; Zulkifli, Zainal; Ismail, Salwani

    2016-01-01

    The innovation of penicillin by Dr Alexander Fleming in 1928 and its use in clinical practice saved many lives, especially during the Second World War. Tuberculosis still carries a significant public health threat and has re-emerged over the past two decades, even in modern countries where tuberculosis was thought to be eliminated. The World Health Organization defines antimicrobial resistance as the resistance of a microorganism to an antimicrobial drug that was initially effective for treatment of infections caused by the microbe. Therefore, the findings of the current study will provide data to enable the design of a new educational program to better equip our students in confronting antimicrobial resistance. This study was a cross-sectional, questionnaire-based survey, which was undertaken in the Faculty of Medicine, Universiti Sultan Zainal Abidin, Kuala Terengganu, Malaysia. The study participants were students of the Bachelor of Medicine and Bachelor of Surgery program (MBBS) of Year III, IV, and V. A total of 142 out of 164 (86%) medical students returned the questionnaire. Specifically, the year-wise breakdown of responses was 29% (41), 39% (55), and 32% (45) for Year III, IV, and V, respectively. Among the study respondents, 28% (40) were male, and the remaining 72% (102) were female. In all, 67% of the participants felt more confident in “making an accurate diagnosis of infection/sepsis.” The majority (88%) of the study participants stated that they would like more training on antibiotic selection. This research has found that there is a gap between theoretical input and clinical practice; the students are demanding more educational intervention to face the threat of antimicrobial resistance. PMID:27042083

  16. Effects of a Combined Aerobic and Resistance Exercise Program on C1q/TNF-Related Protein-3 (CTRP-3) and CTRP-5 Levels

    PubMed Central

    Choi, Hae Yoon; Park, Ji Woo; Lee, Namseok; Hwang, Soon Young; Cho, Geum Ju; Hong, Ho Cheol; Yoo, Hye Jin; Hwang, Taek Geun; Kim, Seon Mi; Baik, Sei Hyun; Park, Kyong Soo; Youn, Byung-Soo; Choi, Kyung Mook

    2013-01-01

    OBJECTIVE To examine the effect of a combined exercise program on C1q/tumor necrosis factor-related protein (CTRP) 3 and CTRP-5 levels and novel adiponectin paralogs suggested to be links between metabolism and inflammation and to evaluate sex differences and association with cardiometabolic risk factors in humans with use of a newly developed ELISA. RESEARCH DESIGN AND METHODS This cross-sectional study explored the implications of CTRP-3 and CTRP-5 on cardiometabolic parameters in 453 nondiabetic Korean adults. In addition, we evaluated the impact of a 3-month combined exercise program on CTRP-3 and CTRP-5 levels in 76 obese women. The exercise program consisted of 45 min of aerobic exercise at an intensity of 60–75% of the age-predicted maximum heart rate (300 kcal/session) and 20 min of resistance training (100 kcal/session) five times per week. RESULTS Both CTRP-3 and CTRP-5 concentrations were significantly higher in women (P < 0.001) than in men (P = 0.030). In a multiple stepwise regression analysis, CTRP-3 levels were independently associated with age, sex, and triglyceride, LDL cholesterol, adiponectin, and retinol-binding protein 4 (RBP4) levels (R2 = 0.182). After 3 months of a combined exercise program, cardiometabolic risk factors, including components of metabolic syndrome, insulin resistance, and RBP4 levels, decreased significantly. In particular, CTRP-3 levels decreased significantly (median [interquartile range] 444.3 [373.8–535.0] to 374.4 [297.2–435.9], P < 0.001), whereas CTRP-5 levels were slightly increased (34.1 [28.6–44.3] to 38.4 [29.8–55.1], P = 0.048). CONCLUSIONS A 3-month combined exercise program significantly decreased CTRP-3 levels and modestly increased CTRP-5 levels in obese Korean women. PMID:23780948

  17. High-level carbapenem resistance in a Citrobacter freundii clinical isolate is due to a combination of KPC-2 production and decreased porin expression.

    PubMed

    Zhang, Rong; Yang, Lijiang; Cai, Jia Chang; Zhou, Hong Wei; Chen, Gong-Xiang

    2008-03-01

    An imipenem-resistant isolate of Citrobacter freundii ZJ163 (MIC 256 microg ml(-1)) isolated from a Chinese hospital was investigated. The C. freundii ZJ163 isolate exhibited high-level resistance to carbapenems, penicillins, cephalosporins, cefoxitin, aztreonam, quinolones and aminoglycosides. Isoelectric focusing (IEF) demonstrated three beta-lactamases with pIs of 5.4 (TEM-1), 6.7 (KPC-2) and 7.9 (CTX-M-14). Two different transconjugants (types A and B) were obtained by conjugation studies. The type A transconjugant exhibited reduced susceptibility or resistance to penicillins, cephalosporins and aztreonam, but was susceptible to carbapenems, quinolones and aminoglycosides. The antimicrobial susceptibility patterns of the type B transconjugant were similar to that of type A, except for its significantly reduced carbapenem susceptibility (imipenem MIC 2 microg ml(-1)). IEF, specific PCRs and DNA sequence analysis indicated that the type A transconjugant produced CTX-M-14 beta-lactamase with a pI of 7.9, that the type B transconjugant produced KPC-2 beta-lactamase with a pI of 6.7 and that the beta-lactamase with a pI of 5.4 was TEM-1. PCR analysis and sequencing confirmed the presence of the ampC gene in the chromosomal DNA from C. freundii ZJ163, although no activity of AmpC beta-lactamase was detected by IEF. Urea/SDS-PAGE analysis of outer-membrane proteins revealed that the levels of the 41 and 38 kDa porins were decreased in C. freundii ZJ163. It was concluded that production of KPC-2 combined with decreased expression of porins contributes to high-level resistance to carbapenems in C. freundii ZJ163.

  18. Dietary intake and serum and hair concentrations of minerals and their relationship with serum lipids and glucose levels in hypertensive and obese patients with insulin resistance.

    PubMed

    Suliburska, Joanna; Bogdański, Paweł; Pupek-Musialik, Danuta; Krejpcio, Zbigniew

    2011-02-01

    Inadequate minerals intake, as well as disruption of some metabolic processes in which microelements are cofactors, are suggested to lead to the development of hypertension. The role of minerals in the pathogenesis of hypertension still remains to be explained. In the present study, we sought to determine associations between serum and hair mineral concentrations and serum lipids and glucose levels. Forty obese hypertensive subjects with insulin resistance and 40 healthy volunteers were recruited in the study. Blood pressure, BMI, and insulin resistance were recorded in all subjects. Levels of lipids, glucose, sodium and potassium, iron, copper, zinc, magnesium, and calcium were assessed in serum. Iron, copper, zinc, magnesium, and calcium were assessed in hair. Dietary intake of the analyzed minerals was estimated. We found distinctly higher concentrations of serum iron and serum and hair calcium as well as markedly lower levels of hair zinc in the hypertensive subjects. The study group manifested also significantly lower daily intake of calcium, magnesium, and iron. We observed a relationship between the concentrations of iron, zinc, and copper in serum and hair and high and low range of cholesterol, triglycerides, and glucose serum levels in the studied patients. Moreover, this study demonstrated significant correlation between serum and hair concentrations of selected minerals and their dietary intake and levels of serum lipids and glucose and blood pressure in the study and the control groups. The obtained results seem to indicate the association between lipid and glucose metabolism and iron, copper, zinc, and calcium concentrations in blood and hair of hypertensive and obese patients with insulin resistance.

  19. Lemon detox diet reduced body fat, insulin resistance, and serum hs-CRP level without hematological changes in overweight Korean women.

    PubMed

    Kim, Mi Joung; Hwang, Jung Hyun; Ko, Hyun Ji; Na, Hye Bock; Kim, Jung Hee

    2015-05-01

    The lemon detox program is a very low-calorie diet which consists of a mixture of organic maple and palm syrups, and lemon juice for abstinence period of 7 days. We hypothesized that the lemon detox program would reduce body weight, body fat mass, thus lowering insulin resistance and known risk factors of cardiovascular disease. We investigated anthropometric indices, insulin sensitivity, levels of serum adipokines, and inflammatory markers in overweight Korean women before and after clinical intervention trial. Eighty-four premenopausal women were randomly divided into 3 groups: a control group without diet restriction (Normal-C), a pair-fed placebo diet group (Positive-C), and a lemon detox diet group (Lemon-D). The intervention period was 11 days total: 7 days with the lemon detox juice or the placebo juice, and then 4 days with transitioning food. Changes in body weight, body mass index, percentage body fat, and waist-hip ratio were significantly greater in the Lemon-D and Positive-C groups compared to the Normal-C group. Serum insulin level, homeostasis model assessment insulin resistance scores, leptin, and adiponectin levels decreased in the Lemon-D and Positive-C groups. Serum high-sensitive C-reactive protein (hs-CRP) levels were also reduced only in the Lemon-D group. Hemoglobin and hematocrit levels remained stable in the Lemon-D group while they decreased in the Positive-C and Normal-C groups. Therefore, we suppose that the lemon detox program reduces body fat and insulin resistance through caloric restriction and might have a potential beneficial effect on risk factors for cardiovascular disease related to circulating hs-CRP reduction without hematological changes.

  20. Changes in plasma D-serine, L-serine, and glycine levels in treatment-resistant schizophrenia before and after clozapine treatment.

    PubMed

    Yamamori, Hidenaga; Hashimoto, Ryota; Fujita, Yuko; Numata, Shusuke; Yasuda, Yuka; Fujimoto, Michiko; Ohi, Kazutaka; Umeda-Yano, Satomi; Ito, Akira; Ohmori, Tetsuro; Hashimoto, Kenji; Takeda, Masatoshi

    2014-10-17

    Hypofunction of the N-methyl-d-aspartate (NMDA) subtype of glutamate receptors may be involved in the pathophysiology of schizophrenia. Many studies have investigated peripheral NMDA receptor-related glutamatergic amino acid levels because of their potential as biological markers. Peripheral d-serine levels and the ratio of d-serine to total serine have been reported to be significantly lower in patients with schizophrenia than in controls. Peripheral d-serine levels and the d-/l-serine ratio have also been reported to significantly increase in patients with schizophrenia as their clinical symptoms improve from the time of admission to the time of discharge. In this study, we examined whether peripheral NMDA receptor-related glutamatergic amino acids levels were altered in patients with treatment-resistant schizophrenia compared to controls and whether these peripheral amino acids levels were altered by clozapine treatment. Twenty-two patients with treatment-resistant schizophrenia and 22 age- and gender-matched healthy controls were enrolled. The plasma levels of d-serine, l-serine, glycine, glutamate, and glutamine were measured before and after clozapine treatment. We found that the plasma levels of d-serine and the d-/l-serine ratio were significantly lower in the patients before clozapine treatment than in the controls. The d-/l-serine ratio was significantly increased by clozapine treatment in patients, and no significant difference was observed in the plasma levels of d-serine and the d-/l-serine ratio between the patients after clozapine treatment and the controls. We also found that plasma glycine levels and the glycine/l-serine ratio were significantly increased following clozapine treatment in the patients, and the glycine/l-serine ratio was significantly higher in the patients after clozapine treatment than in the controls. There was no significant difference in the plasma levels of glutamate and glutamine both between the controls and patients and

  1. High-level fluoroquinolone resistant Salmonella enterica serovar Kentucky ST198 epidemic clone with IncA/C conjugative plasmid carrying bla(CTX-M-25) gene.

    PubMed

    Wasyl, Dariusz; Kern-Zdanowicz, Izabela; Domańska-Blicharz, Katarzyna; Zając, Magdalena; Hoszowski, Andrzej

    2015-01-30

    Multidrug resistant Salmonella Kentucky strains have been isolated from turkeys in Poland since 2009. Multiple mutations within chromosomal genes gyrA and parC were responsible for high-level ciprofloxacin resistance. One of the isolates was extended spectrum β-lactamase- (ESBL) positive: the strain 1643/2010 carried a conjugative 167,779 bps plasmid of IncA/C family. The sequence analysis revealed that it carried a blaCTX-M-25 gene and an integron with another β-lactamase encoding gene-blaOXA-21. This is the first known report of a CTX-M-25 encoding gene both in Poland and in Salmonella Kentucky world-wide, as well as in the IncA/C plasmid. Analysis of the integron showed a novel arrangement of gene cassettes-aacA4, aacC-A1 and blaOXA-21 where the latter might result from an intergeneric gene transfer. The study confirmed Salmonella Kentucky population isolated in Poland belongs to global epidemics of high level fluoroquinolone resistant clone ST198 that can carry rare β-lactamase genes.

  2. Identification of genes differentially expressed during early interactions between the stem rot fungus (Sclerotium rolfsii) and peanut (Arachis hypogaea) cultivars with increasing disease resistance levels.

    PubMed

    Jogi, Ansuya; Kerry, John W; Brenneman, Timothy B; Leebens-Mack, James H; Gold, Scott E

    2016-03-01