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Sample records for active matrix readout

  1. Active pixel sensor array with multiresolution readout

    NASA Technical Reports Server (NTRS)

    Fossum, Eric R. (Inventor); Kemeny, Sabrina E. (Inventor); Pain, Bedabrata (Inventor)

    1999-01-01

    An imaging device formed as a monolithic complementary metal oxide semiconductor integrated circuit in an industry standard complementary metal oxide semiconductor process, the integrated circuit including a focal plane array of pixel cells, each one of the cells including a photogate overlying the substrate for accumulating photo-generated charge in an underlying portion of the substrate and a charge coupled device section formed on the substrate adjacent the photogate having a sensing node and at least one charge coupled device stage for transferring charge from the underlying portion of the substrate to the sensing node. There is also a readout circuit, part of which can be disposed at the bottom of each column of cells and be common to all the cells in the column. The imaging device can also include an electronic shutter formed on the substrate adjacent the photogate, and/or a storage section to allow for simultaneous integration. In addition, the imaging device can include a multiresolution imaging circuit to provide images of varying resolution. The multiresolution circuit could also be employed in an array where the photosensitive portion of each pixel cell is a photodiode. This latter embodiment could further be modified to facilitate low light imaging.

  2. Low-power priority Address-Encoder and Reset-Decoder data-driven readout for Monolithic Active Pixel Sensors for tracker system

    NASA Astrophysics Data System (ADS)

    Yang, P.; Aglieri, G.; Cavicchioli, C.; Chalmet, P. L.; Chanlek, N.; Collu, A.; Gao, C.; Hillemanns, H.; Junique, A.; Kofarago, M.; Keil, M.; Kugathasan, T.; Kim, D.; Kim, J.; Lattuca, A.; Marin Tobon, C. A.; Marras, D.; Mager, M.; Martinengo, P.; Mazza, G.; Mugnier, H.; Musa, L.; Puggioni, C.; Rousset, J.; Reidt, F.; Riedler, P.; Snoeys, W.; Siddhanta, S.; Usai, G.; van Hoorne, J. W.; Yi, J.

    2015-06-01

    Active Pixel Sensors used in High Energy Particle Physics require low power consumption to reduce the detector material budget, low integration time to reduce the possibilities of pile-up and fast readout to improve the detector data capability. To satisfy these requirements, a novel Address-Encoder and Reset-Decoder (AERD) asynchronous circuit for a fast readout of a pixel matrix has been developed. The AERD data-driven readout architecture operates the address encoding and reset decoding based on an arbitration tree, and allows us to readout only the hit pixels. Compared to the traditional readout structure of the rolling shutter scheme in Monolithic Active Pixel Sensors (MAPS), AERD can achieve a low readout time and a low power consumption especially for low hit occupancies. The readout is controlled at the chip periphery with a signal synchronous with the clock, allows a good digital and analogue signal separation in the matrix and a reduction of the power consumption. The AERD circuit has been implemented in the TowerJazz 180 nm CMOS Imaging Sensor (CIS) process with full complementary CMOS logic in the pixel. It works at 10 MHz with a matrix height of 15 mm. The energy consumed to read out one pixel is around 72 pJ. A scheme to boost the readout speed to 40 MHz is also discussed. The sensor chip equipped with AERD has been produced and characterised. Test results including electrical beam measurement are presented.

  3. Transversal-readout CMOS active pixel image sensor

    NASA Astrophysics Data System (ADS)

    Miyatake, Shigehiro; Ishida, Kouichi; Morimoto, Takashi; Masaki, Yasuo; Tanabe, Hideki

    2001-05-01

    This paper presents a CMOS active pixel image sensor (APS) with a transversal readout architecture that eliminates the vertically striped fixed pattern noise (FPN). There are two kinds of FPNs for CMOS APSs. One originates form the pixel- to-pixel variation in dark current and source-follower threshold voltage, and the other from the column-to-column variation in column readout structures. The former may become invisible in the future due to process improvements. However, the latter, which result sin a vertically striped FPN, is and will be conspicuous without some subtraction because of the correlation in the vertical direction. The pixel consists of a photodiode, a row- and a column-reset transistor, a source follower input transistor, and a column-select transistor instead of the row-select transistor in conventional CMOS APSs. The column-select transistor is connected to a signal line, which runs horizontally instead of vertically. Every horizontal signal line is merged into a single vertical signal line via a row- select transistor, which can be made large enough to make its on-resistence variation negligible because of its low driving frequency. Therefore, the sensor has neither a vertical nor horizontal stripe FPN.

  4. Digital radiography using amorphous selenium: photoconductively activated switch (PAS) readout system.

    PubMed

    Reznik, Nikita; Komljenovic, Philip T; Germann, Stephen; Rowlands, John A

    2008-03-01

    A new amorphous selenium (a-Se) digital radiography detector is introduced. The proposed detector generates a charge image in the a-Se layer in a conventional manner, which is stored on electrode pixels at the surface of the a-Se layer. A novel method, called photoconductively activated switch (PAS), is used to read out the latent x-ray charge image. The PAS readout method uses lateral photoconduction at the a-Se surface which is a revolutionary modification of the bulk photoinduced discharge (PID) methods. The PAS method addresses and eliminates the fundamental weaknesses of the PID methods--long readout times and high readout noise--while maintaining the structural simplicity and high resolution for which PID optical readout systems are noted. The photoconduction properties of the a-Se surface were investigated and the geometrical design for the electrode pixels for a PAS radiography system was determined. This design was implemented in a single pixel PAS evaluation system. The results show that the PAS x-ray induced output charge signal was reproducible and depended linearly on the x-ray exposure in the diagnostic exposure range. Furthermore, the readout was reasonably rapid (10 ms for pixel discharge). The proposed detector allows readout of half a pixel row at a time (odd pixels followed by even pixels), thus permitting the readout of a complete image in 30 s for a 40 cm x 40 cm detector with the potential of reducing that time by using greater readout light intensity. This demonstrates that a-Se based x-ray detectors using photoconductively activated switches could form a basis for a practical integrated digital radiography system. PMID:18404939

  5. Quantification of extracellular matrix proteins from a rat lung scaffold to provide a molecular readout for tissue engineering.

    PubMed

    Hill, Ryan C; Calle, Elizabeth A; Dzieciatkowska, Monika; Niklason, Laura E; Hansen, Kirk C

    2015-04-01

    The use of extracellular matrix (ECM) scaffolds, derived from decellularized tissues for engineered organ generation, holds enormous potential in the field of regenerative medicine. To support organ engineering efforts, we developed a targeted proteomics method to extract and quantify extracellular matrix components from tissues. Our method provides more complete and accurate protein characterization than traditional approaches. This is accomplished through the analysis of both the chaotrope-soluble and -insoluble protein fractions and using recombinantly generated stable isotope labeled peptides for endogenous protein quantification. Using this approach, we have generated 74 peptides, representing 56 proteins to quantify protein in native (nondecellularized) and decellularized lung matrices. We have focused on proteins of the ECM and additional intracellular proteins that are challenging to remove during the decellularization procedure. Results indicate that the acellular lung scaffold is predominantly composed of structural collagens, with the majority of these proteins found in the insoluble ECM, a fraction that is often discarded using widely accepted proteomic methods. The decellularization procedure removes over 98% of intracellular proteins evaluated and retains, to varying degrees, proteoglycans and glycoproteins of the ECM. Accurate characterization of ECM proteins from tissue samples will help advance organ engineering efforts by generating a molecular readout that can be correlated with functional outcome to drive the next generation of engineered organs.

  6. Quantification of Extracellular Matrix Proteins from a Rat Lung Scaffold to Provide a Molecular Readout for Tissue Engineering*

    PubMed Central

    Hill, Ryan C.; Calle, Elizabeth A.; Dzieciatkowska, Monika; Niklason, Laura E.; Hansen, Kirk C.

    2015-01-01

    The use of extracellular matrix (ECM)1 scaffolds, derived from decellularized tissues for engineered organ generation, holds enormous potential in the field of regenerative medicine. To support organ engineering efforts, we developed a targeted proteomics method to extract and quantify extracellular matrix components from tissues. Our method provides more complete and accurate protein characterization than traditional approaches. This is accomplished through the analysis of both the chaotrope-soluble and -insoluble protein fractions and using recombinantly generated stable isotope labeled peptides for endogenous protein quantification. Using this approach, we have generated 74 peptides, representing 56 proteins to quantify protein in native (nondecellularized) and decellularized lung matrices. We have focused on proteins of the ECM and additional intracellular proteins that are challenging to remove during the decellularization procedure. Results indicate that the acellular lung scaffold is predominantly composed of structural collagens, with the majority of these proteins found in the insoluble ECM, a fraction that is often discarded using widely accepted proteomic methods. The decellularization procedure removes over 98% of intracellular proteins evaluated and retains, to varying degrees, proteoglycans and glycoproteins of the ECM. Accurate characterization of ECM proteins from tissue samples will help advance organ engineering efforts by generating a molecular readout that can be correlated with functional outcome to drive the next generation of engineered organs. PMID:25660013

  7. Time resolution of the plastic scintillator strips with matrix photomultiplier readout for J-PET tomograph.

    PubMed

    Moskal, P; Rundel, O; Alfs, D; Bednarski, T; Białas, P; Czerwiński, E; Gajos, A; Giergiel, K; Gorgol, M; Jasińska, B; Kamińska, D; Kapłon, Ł; Korcyl, G; Kowalski, P; Kozik, T; Krzemień, W; Kubicz, E; Niedźwiecki, Sz; Pałka, M; Raczyński, L; Rudy, Z; Sharma, N G; Słomski, A; Silarski, M; Strzelecki, A; Wieczorek, A; Wiślicki, W; Witkowski, P; Zieliński, M; Zoń, N

    2016-03-01

    Recent tests of a single module of the Jagiellonian Positron Emission Tomography system (J-PET) consisting of 30 cm long plastic scintillator strips have proven its applicability for the detection of annihilation quanta (0.511 MeV) with a coincidence resolving time (CRT) of 0.266 ns. The achieved resolution is almost by a factor of two better with respect to the current TOF-PET detectors and it can still be improved since, as it is shown in this article, the intrinsic limit of time resolution for the determination of time of the interaction of 0.511 MeV gamma quanta in plastic scintillators is much lower. As the major point of the article, a method allowing to record timestamps of several photons, at two ends of the scintillator strip, by means of matrix of silicon photomultipliers (SiPM) is introduced. As a result of simulations, conducted with the number of SiPM varying from 4 to 42, it is shown that the improvement of timing resolution saturates with the growing number of photomultipliers, and that the [Formula: see text] configuration at two ends allowing to read twenty timestamps, constitutes an optimal solution. The conducted simulations accounted for the emission time distribution, photon transport and absorption inside the scintillator, as well as quantum efficiency and transit time spread of photosensors, and were checked based on the experimental results. Application of the [Formula: see text] matrix of SiPM allows for achieving the coincidence resolving time in positron emission tomography of [Formula: see text]0.170 ns for 15 cm axial field-of-view (AFOV) and [Formula: see text]0.365 ns for 100 cm AFOV. The results open perspectives for construction of a cost-effective TOF-PET scanner with significantly better TOF resolution and larger AFOV with respect to the current TOF-PET modalities. PMID:26895187

  8. Time resolution of the plastic scintillator strips with matrix photomultiplier readout for J-PET tomograph

    NASA Astrophysics Data System (ADS)

    Moskal, P.; Rundel, O.; Alfs, D.; Bednarski, T.; Białas, P.; Czerwiński, E.; Gajos, A.; Giergiel, K.; Gorgol, M.; Jasińska, B.; Kamińska, D.; Kapłon, Ł.; Korcyl, G.; Kowalski, P.; Kozik, T.; Krzemień, W.; Kubicz, E.; Niedźwiecki, Sz; Pałka, M.; Raczyński, L.; Rudy, Z.; Sharma, N. G.; Słomski, A.; Silarski, M.; Strzelecki, A.; Wieczorek, A.; Wiślicki, W.; Witkowski, P.; Zieliński, M.; Zoń, N.

    2016-03-01

    Recent tests of a single module of the Jagiellonian Positron Emission Tomography system (J-PET) consisting of 30 cm long plastic scintillator strips have proven its applicability for the detection of annihilation quanta (0.511 MeV) with a coincidence resolving time (CRT) of 0.266 ns. The achieved resolution is almost by a factor of two better with respect to the current TOF-PET detectors and it can still be improved since, as it is shown in this article, the intrinsic limit of time resolution for the determination of time of the interaction of 0.511 MeV gamma quanta in plastic scintillators is much lower. As the major point of the article, a method allowing to record timestamps of several photons, at two ends of the scintillator strip, by means of matrix of silicon photomultipliers (SiPM) is introduced. As a result of simulations, conducted with the number of SiPM varying from 4 to 42, it is shown that the improvement of timing resolution saturates with the growing number of photomultipliers, and that the 2× 5 configuration at two ends allowing to read twenty timestamps, constitutes an optimal solution. The conducted simulations accounted for the emission time distribution, photon transport and absorption inside the scintillator, as well as quantum efficiency and transit time spread of photosensors, and were checked based on the experimental results. Application of the 2× 5 matrix of SiPM allows for achieving the coincidence resolving time in positron emission tomography of ≈ 0.170 ns for 15 cm axial field-of-view (AFOV) and ≈ 0.365 ns for 100 cm AFOV. The results open perspectives for construction of a cost-effective TOF-PET scanner with significantly better TOF resolution and larger AFOV with respect to the current TOF-PET modalities.

  9. Time resolution of the plastic scintillator strips with matrix photomultiplier readout for J-PET tomograph.

    PubMed

    Moskal, P; Rundel, O; Alfs, D; Bednarski, T; Białas, P; Czerwiński, E; Gajos, A; Giergiel, K; Gorgol, M; Jasińska, B; Kamińska, D; Kapłon, Ł; Korcyl, G; Kowalski, P; Kozik, T; Krzemień, W; Kubicz, E; Niedźwiecki, Sz; Pałka, M; Raczyński, L; Rudy, Z; Sharma, N G; Słomski, A; Silarski, M; Strzelecki, A; Wieczorek, A; Wiślicki, W; Witkowski, P; Zieliński, M; Zoń, N

    2016-03-01

    Recent tests of a single module of the Jagiellonian Positron Emission Tomography system (J-PET) consisting of 30 cm long plastic scintillator strips have proven its applicability for the detection of annihilation quanta (0.511 MeV) with a coincidence resolving time (CRT) of 0.266 ns. The achieved resolution is almost by a factor of two better with respect to the current TOF-PET detectors and it can still be improved since, as it is shown in this article, the intrinsic limit of time resolution for the determination of time of the interaction of 0.511 MeV gamma quanta in plastic scintillators is much lower. As the major point of the article, a method allowing to record timestamps of several photons, at two ends of the scintillator strip, by means of matrix of silicon photomultipliers (SiPM) is introduced. As a result of simulations, conducted with the number of SiPM varying from 4 to 42, it is shown that the improvement of timing resolution saturates with the growing number of photomultipliers, and that the [Formula: see text] configuration at two ends allowing to read twenty timestamps, constitutes an optimal solution. The conducted simulations accounted for the emission time distribution, photon transport and absorption inside the scintillator, as well as quantum efficiency and transit time spread of photosensors, and were checked based on the experimental results. Application of the [Formula: see text] matrix of SiPM allows for achieving the coincidence resolving time in positron emission tomography of [Formula: see text]0.170 ns for 15 cm axial field-of-view (AFOV) and [Formula: see text]0.365 ns for 100 cm AFOV. The results open perspectives for construction of a cost-effective TOF-PET scanner with significantly better TOF resolution and larger AFOV with respect to the current TOF-PET modalities.

  10. Active Matrix OLED Test Report

    NASA Technical Reports Server (NTRS)

    Salazar, George

    2013-01-01

    This report focuses on the limited environmental testing of the AMOLED display performed as an engineering evaluation by The NASA Johnson Space Center (JSC)-specifically. EMI. Thermal Vac, and radiation tests. The AMOLED display is an active-matrix Organic Light Emitting Diode (OLED) technology. The testing provided an initial understanding of the technology and its suitability for space applications. Relative to light emitting diode (LED) displays or liquid crystal displays (LCDs), AMOLED displays provide a superior viewing experience even though they are much lighter and smaller, produce higher contrast ratio and richer colors, and require less power to operate than LCDs. However, AMOLED technology has not been demonstrated in a space environment. Therefore, some risks with the technology must be addressed before they can be seriously considered for human spaceflight. The environmental tests provided preliminary performance data on the ability of the display technology to handle some of the simulated induced space/spacecraft environments that an AMOLED display will see during a spacecraft certification test program. This engineering evaluation is part of a Space Act Agreement (SM) between The NASA/JSC and Honeywell International (HI) as a collaborative effort to evaluate the potential use of AMOLED technology for future human spaceflight missions- both government-led and commercial. Under this SM, HI is responsible for doing optical performance evaluation, as well as temperature and touch screen studies. The NASA/JSC is responsible for performing environmental testing comprised of EMI, Thermal Vac, and radiation tests. Additionally, as part of the testing, limited optical data was acquired to assess performance as the display was subjected to the induced environments. The NASA will benefit from this engineering evaluation by understanding AMOLED suitability for future use in space as well as becoming a smarter buyer (or developer) of the technology. HI benefits

  11. A High-Speed, Event-Driven, Active Pixel Sensor Readout for Photon-Counting Microchannel Plate Detectors

    NASA Technical Reports Server (NTRS)

    Kimble, Randy A.; Pain, B.; Norton, T. J.; Haas, P.; Fisher, Richard R. (Technical Monitor)

    2001-01-01

    Silicon array readouts for microchannel plate intensifiers offer several attractive features. In this class of detector, the electron cloud output of the MCP intensifier is converted to visible light by a phosphor; that light is then fiber-optically coupled to the silicon array. In photon-counting mode, the resulting light splashes on the silicon array are recognized and centroided to fractional pixel accuracy by off-chip electronics. This process can result in very high (MCP-limited) spatial resolution for the readout while operating at a modest MCP gain (desirable for dynamic range and long term stability). The principal limitation of intensified CCD systems of this type is their severely limited local dynamic range, as accurate photon counting is achieved only if there are not overlapping event splashes within the frame time of the device. This problem can be ameliorated somewhat by processing events only in pre-selected windows of interest or by using an addressable charge injection device (CID) for the readout array. We are currently pursuing the development of an intriguing alternative readout concept based on using an event-driven CMOS Active Pixel Sensor. APS technology permits the incorporation of discriminator circuitry within each pixel. When coupled with suitable CMOS logic outside the array area, the discriminator circuitry can be used to trigger the readout of small sub-array windows only when and where an event splash has been detected, completely eliminating the local dynamic range problem, while achieving a high global count rate capability and maintaining high spatial resolution. We elaborate on this concept and present our progress toward implementing an event-driven APS readout.

  12. A High-Speed, Event-Driven, Active Pixel Sensor Readout for Photon-Counting Microchannel Plate Detectors

    NASA Technical Reports Server (NTRS)

    Kimble, Randy A.; Pain, Bedabrata; Norton, Timothy J.; Haas, J. Patrick; Oegerle, William R. (Technical Monitor)

    2002-01-01

    Silicon array readouts for microchannel plate intensifiers offer several attractive features. In this class of detector, the electron cloud output of the MCP intensifier is converted to visible light by a phosphor; that light is then fiber-optically coupled to the silicon array. In photon-counting mode, the resulting light splashes on the silicon array are recognized and centroided to fractional pixel accuracy by off-chip electronics. This process can result in very high (MCP-limited) spatial resolution while operating at a modest MCP gain (desirable for dynamic range and long term stability). The principal limitation of intensified CCD systems of this type is their severely limited local dynamic range, as accurate photon counting is achieved only if there are not overlapping event splashes within the frame time of the device. This problem can be ameliorated somewhat by processing events only in pre-selected windows of interest of by using an addressable charge injection device (CID) for the readout array. We are currently pursuing the development of an intriguing alternative readout concept based on using an event-driven CMOS Active Pixel Sensor. APS technology permits the incorporation of discriminator circuitry within each pixel. When coupled with suitable CMOS logic outside the array area, the discriminator circuitry can be used to trigger the readout of small sub-array windows only when and where an event splash has been detected, completely eliminating the local dynamic range problem, while achieving a high global count rate capability and maintaining high spatial resolution. We elaborate on this concept and present our progress toward implementing an event-driven APS readout.

  13. Optically readout write once read many memory with single active organic layer

    NASA Astrophysics Data System (ADS)

    Nguyen, Viet Cuong; Lee, Pooi See

    2016-01-01

    An optically readable write once read many memory (WORM) in Ag/Poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH PPV)/ITO is demonstrated in this work. Utilising characteristics of the organic light emitting diode structure of Ag/MEH PPV/ITO and electrochemical metallization of Ag, a WORM with light emitting capability can be realised. The simple fabrication process and multifunction capability of the device can be useful for future wearable optoelectronics and photomemory applications, where fast and parallel readout can be achieved by photons.

  14. Neutrophil activator of matrix metalloproteinase-2 (NAM).

    PubMed

    Rollo, Ellen E; Hymowitz, Michelle; Schmidt, Cathleen E; Montana, Steve; Foda, Hussein; Zucker, Stanley

    2006-01-01

    We have isolated a novel soluble factor(s), neutrophil activator of matrix metalloproteinases (NAM), secreted by unstimulated normal human peripheral blood neutrophils that causes the activation of cell secreted promatrix metalloproteinase-2 (proMMP-2). Partially purified preparations of NAM have been isolated from the conditioned media of neutrophils employing gelatin-Sepharose chromatography and differential membrane filter centrifugation. NAM activity, as assessed by exposing primary human umbilical vein endothelial cells (HUVEC) or HT1080 cells to NAM followed by gelatin zymography, was seen within one hour. Tissue inhibitor of metalloproteinase-2 (TIMP-2) and hydroxamic acid derived inhibitors of MMPs (CT1746 and BB94) abrogated the activation of proMMP-2 by NAM, while inhibitors of serine and cysteine proteases showed no effect. NAM also produced an increase in TIMP-2 binding to HUVEC and HT1080 cell surfaces that was inhibited by TIMP-2, CT1746, and BB94. Time-dependent increases in MT1-MMP protein and mRNA were seen following the addition of NAM to cells. These data support a role for NAM in cancer dissemination.

  15. An application of CCD read-out technique to neutron distribution measurement using the self-activation method with a CsI scintillator plate

    NASA Astrophysics Data System (ADS)

    Nohtomi, Akihiro; Kurihara, Ryosuke; Kinoshita, Hiroyuki; Honda, Soichiro; Tokunaga, Masaaki; Uno, Heita; Shinsho, Kiyomitsu; Wakabayashi, Genichiro; Koba, Yusuke; Fukunaga, Junichi; Umezu, Yoshiyuki; Nakamura, Yasuhiko; Ohga, Saiji

    2016-10-01

    In our previous paper, the self-activation of an NaI scintillator had been successfully utilized for detecting photo-neutrons around a high-energy X-ray radiotherapy machine; individual optical pulses from the self-activated scintillator are read-out by photo sensors such as a photomultiplier tube (PMT). In the present work, preliminary observations have been performed in order to apply a direct CCD read-out technique to the self-activation method with a CsI scintillator plate using a Pu-Be source and a 10-MV linac. In conclusion, it has been revealed that the CCD read-out technique is applicable to neutron measurement around a high-energy X-ray radiotherapy machine with the self-activation of a CsI plate. Such application may provide a possibility of novel method for simple neutron dose-distribution measurement.

  16. Dual-readout fluorescent assay of protein kinase activity by use of TiO2-coated magnetic microspheres.

    PubMed

    Bai, Jie; Zhao, Yunjie; Wang, Zhibin; Liu, Chenghui; Wang, Yucong; Li, Zhengping

    2013-05-01

    A simple, highly sensitive, and dual-readout fluorescent assay is developed for the detection of protein kinase activity based on the specific recognition utility of TiO2-coated Fe3O4/SiO2 magnetic microspheres (TMSPs) for kinase-induced phosphopeptides. When the fluorophore-labeled substrate peptides are phosphorylated by the kinase reaction, they can bind specifically to the TiO2 layer of TMSPs by means of phosphate groups, resulting in fluorophore enrichment on the TMSP surfaces. The accumulated fluorophores on the TMSPs are proportional to the kinase activity, and the fluorescence signal readout could be run through either direct fluorescent imaging of the TMSPs or measurement of the fluorescence intensity by simply detaching the fluorescent phosphopeptides into the solution. The TMSPs exhibit extremely high selectivity for capturing phosphorylated peptides over the nonphosphorylated ones, resulting in an ultrahigh fluorescence signal-to-background ratio of 42, which is the highest fluorescence change thus far in fluorescent assays for detection of protein kinase activities. Therefore, the proposed fluorescent assay presents high sensitivity, low detection limit of 0.1 milliunit/μL, and wide dynamic range from 0.5 milliunit/μL to 0.5 unit/μL with protein kinase A (PKA) as a model target. Moreover, the TMSP-based fluorescent assay can simultaneously quantify multiple kinase activities with their specific peptides labeled with different dyes. This new strategy is also successfully applied to monitoring drug-triggered PKA activation in cell lysates. Therefore, the TMSP-based fluorescent assay is very promising in high-throughput screening of kinase inhibitors and in highly sensitive detection of kinase activity, and thus it is a valuable tool for development of targeted therapy, clinical diagnosis, and studies of fundamental life science. PMID:23581884

  17. Novel active signal compression in low-noise analog readout at future X-ray FEL facilities

    NASA Astrophysics Data System (ADS)

    Manghisoni, M.; Comotti, D.; Gaioni, L.; Lodola, L.; Ratti, L.; Re, V.; Traversi, G.; Vacchi, C.

    2015-04-01

    This work presents the design of a low-noise front-end implementing a novel active signal compression technique. This feature can be exploited in the design of analog readout channels for application to the next generation free electron laser (FEL) experiments. The readout architecture includes the low-noise charge sensitive amplifier (CSA) with dynamic signal compression, a time variant shaper used to process the signal at the preamplifier output and a 10-bit successive approximation register (SAR) analog-to-digital converter (ADC). The channel will be operated in such a way to cope with the high frame rate (exceeding 1 MHz) foreseen for future XFEL machines. The choice of a 65 nm CMOS technology has been made in order to include all the building blocks in the target pixel pitch of 100 μm. This work has been carried out in the frame of the PixFEL Project funded by the Istituto Nazionale di Fisica Nucleare (INFN), Italy.

  18. MONOLITHIC ACTIVE PIXEL MATRIX WITH BINARY COUNTERS IN AN SOI PROCESS.

    SciTech Connect

    DUPTUCH,G.; YAREMA, R.

    2007-06-07

    The design of a Prototype monolithic active pixel matrix, designed in a 0.15 {micro}m CMOS SOI Process, is presented. The process allowed connection between the electronics and the silicon volume under the layer of buried oxide (BOX). The small size vias traversing through the BOX and implantation of small p-type islands in the n-type bulk result in a monolithic imager. During the acquisition time, all pixels register individual radiation events incrementing the counters. The counting rate is up to 1 MHz per pixel. The contents of counters are shifted out during the readout phase. The designed prototype is an array of 64 x 64 pixels and the pixel size is 26 x 26 {micro}m{sup 2}.

  19. XAMPS Detectors Readout ASIC for LCLS

    SciTech Connect

    Dragone, A; Pratte, J.F.; Rehak, P.; Carini, G.A.; Herbst, R.; O'Connor, P.; Siddons, D.P.; /BNL, NSLS

    2008-12-18

    An ASIC for the readout of signals from X-ray Active Matrix Pixel Sensor (XAMPS) detectors to be used at the Linac Coherent Light Source (LCLS) is presented. The X-ray Pump Probe (XPP) instrument, for which the ASIC has been designed, requires a large input dynamic range on the order of 104 photons at 8 keV with a resolution of half a photon FWHM. Due to the size of the pixel and the length of the readout line, large input capacitance is expected, leading to stringent requirement on the noise optimization. Furthermore, the large number of pixels needed for a good position resolution and the fixed LCLS beam period impose limitations on the time available for the single pixel readout. Considering the periodic nature of the LCLS beam, the ASIC developed for this application is a time-variant system providing low-noise charge integration, filtering and correlated double sampling. In order to cope with the large input dynamic range a charge pump scheme implementing a zero-balance measurement method has been introduced. It provides an on chip 3-bit coarse digital conversion of the integrated charge. The residual charge is sampled using correlated double sampling into analog memory and measured with the required resolution. The first 64 channel prototype of the ASIC has been fabricated in TSMC CMOS 0.25 {micro}m technology. In this paper, the ASIC architecture and performances are presented.

  20. Sensor readout detector circuit

    DOEpatents

    Chu, D.D.; Thelen, D.C. Jr.

    1998-08-11

    A sensor readout detector circuit is disclosed that is capable of detecting sensor signals down to a few nanoamperes or less in a high (microampere) background noise level. The circuit operates at a very low standby power level and is triggerable by a sensor event signal that is above a predetermined threshold level. A plurality of sensor readout detector circuits can be formed on a substrate as an integrated circuit (IC). These circuits can operate to process data from an array of sensors in parallel, with only data from active sensors being processed for digitization and analysis. This allows the IC to operate at a low power level with a high data throughput for the active sensors. The circuit may be used with many different types of sensors, including photodetectors, capacitance sensors, chemically-sensitive sensors or combinations thereof to provide a capability for recording transient events or for recording data for a predetermined period of time following an event trigger. The sensor readout detector circuit has applications for portable or satellite-based sensor systems. 6 figs.

  1. Sensor readout detector circuit

    DOEpatents

    Chu, Dahlon D.; Thelen, Jr., Donald C.

    1998-01-01

    A sensor readout detector circuit is disclosed that is capable of detecting sensor signals down to a few nanoamperes or less in a high (microampere) background noise level. The circuit operates at a very low standby power level and is triggerable by a sensor event signal that is above a predetermined threshold level. A plurality of sensor readout detector circuits can be formed on a substrate as an integrated circuit (IC). These circuits can operate to process data from an array of sensors in parallel, with only data from active sensors being processed for digitization and analysis. This allows the IC to operate at a low power level with a high data throughput for the active sensors. The circuit may be used with many different types of sensors, including photodetectors, capacitance sensors, chemically-sensitive sensors or combinations thereof to provide a capability for recording transient events or for recording data for a predetermined period of time following an event trigger. The sensor readout detector circuit has applications for portable or satellite-based sensor systems.

  2. Focal plane infrared readout circuit

    NASA Technical Reports Server (NTRS)

    Pain, Bedabrata (Inventor)

    2002-01-01

    An infrared imager, such as a spectrometer, includes multiple infrared photodetectors and readout circuits for reading out signals from the photodetectors. Each readout circuit includes a buffered direct injection input circuit including a differential amplifier with active feedback provided through an injection transistor. The differential amplifier includes a pair of input transistors, a pair of cascode transistors and a current mirror load. Photocurrent from a photodetector can be injected onto an integration capacitor in the readout circuit with high injection efficiency at high speed. A high speed, low noise, wide dynamic range linear infrared multiplexer array for reading out infrared detectors with large capacitances can be achieved even when short exposure times are used. The effect of image lag can be reduced.

  3. Cellular contractility and extracellular matrix stiffness regulate matrix metalloproteinase activity in pancreatic cancer cells.

    PubMed

    Haage, Amanda; Schneider, Ian C

    2014-08-01

    The pathogenesis of cancer is often driven by local invasion and metastasis. Recently, mechanical properties of the tumor microenvironment have been identified as potent regulators of invasion and metastasis, while matrix metalloproteinases (MMPs) are classically known as significant enhancers of cancer cell migration and invasion. Here we have been able to sensitively measure MMP activity changes in response to specific extracellular matrix (ECM) environments and cell contractility states. Cells of a pancreatic cancer cell line, Panc-1, up-regulate MMP activities between 3- and 10-fold with increased cell contractility. Conversely, they down-regulate MMP activities when contractility is blocked to levels seen with pan-MMP activity inhibitors. Similar, albeit attenuated, responses are seen in other pancreatic cancer cell lines, BxPC-3 and AsPC-1. In addition, MMP activity was modulated by substrate stiffness, collagen gel concentration, and the degree of collagen cross-linking, when cells were plated on collagen gels ranging from 0.5 to 5 mg/ml that span the physiological range of substrate stiffness (50-2000 Pa). Panc-1 cells showed enhanced MMP activity on stiffer substrates, whereas BxPC-3 and AsPC-1 cells showed diminished MMP activity. In addition, eliminating heparan sulfate proteoglycans using heparinase completely abrogated the mechanical induction of MMP activity. These results demonstrate the first functional link between MMP activity, contractility, and ECM stiffness and provide an explanation as to why stiffer environments result in enhanced cell migration and invasion.

  4. Google matrix of the world network of economic activities

    NASA Astrophysics Data System (ADS)

    Kandiah, Vivek; Escaith, Hubert; Shepelyansky, Dima L.

    2015-07-01

    Using the new data from the OECD-WTO world network of economic activities we construct the Google matrix G of this directed network and perform its detailed analysis. The network contains 58 countries and 37 activity sectors for years 1995 and 2008. The construction of G, based on Markov chain transitions, treats all countries on equal democratic grounds while the contribution of activity sectors is proportional to their exchange monetary volume. The Google matrix analysis allows to obtain reliable ranking of countries and activity sectors and to determine the sensitivity of CheiRank-PageRank commercial balance of countries in respect to price variations and labor cost in various countries. We demonstrate that the developed approach takes into account multiplicity of network links with economy interactions between countries and activity sectors thus being more efficient compared to the usual export-import analysis. The spectrum and eigenstates of G are also analyzed being related to specific activity communities of countries.

  5. Sparse matrix approximation method for an active optical control system

    NASA Astrophysics Data System (ADS)

    Murphy, Timothy P.; Lyon, Richard G.; Dorband, John E.; Hollis, Jan M.

    2001-12-01

    We develop a sparse matrix approximation method to decompose a wave front into a basis set of actuator influence functions for an active optical system consisting of a deformable mirror and a segmented primary mirror. The wave front used is constructed by Zernike polynomials to simulate the output of a phase-retrieval algorithm. Results of a Monte Carlo simulation of the optical control loop are compared with the standard, nonsparse approach in terms of accuracy and precision, as well as computational speed and memory. The sparse matrix approximation method can yield more than a 50-fold increase in the speed and a 20-fold-reduction in matrix size and a commensurate decrease in required memory, with less than 10% degradation in solution accuracy. Our method is also shown to be better than when elements are selected for the sparse matrix on a magnitude basis alone. We show that the method developed is a viable alternative to use of the full control matrix in a phase-retrieval-based active optical control system.

  6. Sparse matrix approximation method for an active optical control system.

    PubMed

    Murphy, T P; Lyon, R G; Dorband, J E; Hollis, J M

    2001-12-10

    We develop a sparse matrix approximation method to decompose a wave front into a basis set of actuator influence functions for an active optical system consisting of a deformable mirror and a segmented primary mirror. The wave front used is constructed by Zernike polynomials to simulate the output of a phase-retrieval algorithm. Results of a Monte Carlo simulation of the optical control loop are compared with the standard, nonsparse approach in terms of accuracy and precision, as well as computational speed and memory. The sparse matrix approximation method can yield more than a 50-fold increase in the speed and a 20-fold reduction in matrix size and a commensurate decrease in required memory, with less than 10% degradation in solution accuracy. Our method is also shown to be better than when elements are selected for the sparse matrix on a magnitude basis alone. We show that the method developed is a viable alternative to use of the full control matrix in a phase-retrieval-based active optical control system. PMID:18364958

  7. Extracellular Matrix Stiffness Regulates Osteogenic Differentiation through MAPK Activation

    PubMed Central

    Hwang, Jun-Ha; Byun, Mi Ran; Kim, A. Rum; Kim, Kyung Min; Cho, Hang Jun; Lee, Yo Han; Kim, Juwon; Jeong, Mi Gyeong; Hwang, Eun Sook; Hong, Jeong-Ho

    2015-01-01

    Mesenchymal stem cell (MSC) differentiation is regulated by the extracellular matrix (ECM) through activation of intracellular signaling mediators. The stiffness of the ECM was shown to be an important regulatory factor for MSC differentiation, and transcriptional coactivator with PDZ-binding motif (TAZ) was identified as an effector protein for MSC differentiation. However, the detailed underlying mechanism regarding the role of ECM stiffness and TAZ in MSC differentiation is not yet fully understood. In this report, we showed that ECM stiffness regulates MSC fate through ERK or JNK activation. Specifically, a stiff hydrogel matrix stimulates osteogenic differentiation concomitant with increased nuclear localization of TAZ, but inhibits adipogenic differentiation. ERK and JNK activity was significantly increased in cells cultured on a stiff hydrogel. TAZ activation was induced by ERK or JNK activation on a stiff hydrogel because exposure to an ERK or JNK inhibitor significantly decreased the nuclear localization of TAZ, indicating that ECM stiffness-induced ERK or JNK activation is important for TAZ-driven osteogenic differentiation. Taken together, these results suggest that ECM stiffness regulates MSC differentiation through ERK or JNK activation. PMID:26262877

  8. Extracellular Matrix Stiffness Regulates Osteogenic Differentiation through MAPK Activation.

    PubMed

    Hwang, Jun-Ha; Byun, Mi Ran; Kim, A Rum; Kim, Kyung Min; Cho, Hang Jun; Lee, Yo Han; Kim, Juwon; Jeong, Mi Gyeong; Hwang, Eun Sook; Hong, Jeong-Ho

    2015-01-01

    Mesenchymal stem cell (MSC) differentiation is regulated by the extracellular matrix (ECM) through activation of intracellular signaling mediators. The stiffness of the ECM was shown to be an important regulatory factor for MSC differentiation, and transcriptional coactivator with PDZ-binding motif (TAZ) was identified as an effector protein for MSC differentiation. However, the detailed underlying mechanism regarding the role of ECM stiffness and TAZ in MSC differentiation is not yet fully understood. In this report, we showed that ECM stiffness regulates MSC fate through ERK or JNK activation. Specifically, a stiff hydrogel matrix stimulates osteogenic differentiation concomitant with increased nuclear localization of TAZ, but inhibits adipogenic differentiation. ERK and JNK activity was significantly increased in cells cultured on a stiff hydrogel. TAZ activation was induced by ERK or JNK activation on a stiff hydrogel because exposure to an ERK or JNK inhibitor significantly decreased the nuclear localization of TAZ, indicating that ECM stiffness-induced ERK or JNK activation is important for TAZ-driven osteogenic differentiation. Taken together, these results suggest that ECM stiffness regulates MSC differentiation through ERK or JNK activation.

  9. High Matrix Metalloproteinase Activity is a Hallmark of Periapical Granulomas

    PubMed Central

    de Paula e Silva, Francisco Wanderley Garcia; D'Silva, Nisha J.; da Silva, Léa Assed Bezerra; Kapila, Yvonne Lorraine

    2009-01-01

    Introduction Inability to distinguish periapical cysts from granulomas prior to performing root canal treatment leads to uncertainty in treatment outcomes, because cysts have lower healing rates. Searching for differential expression of molecules within cysts or granulomas could provide information with regard to the identity of the lesion or suggest mechanistic differences that may form the basis for future therapeutic intervention. Thus, we investigated whether granulomas and cysts exhibit differential expression of extracellular matrix (ECM) molecules. Methods Human periapical granulomas, periapical cysts, and healthy periodontal ligament tissues were used to investigate the differential expression of ECM molecules by microarray analysis. Since matrix metalloproteinases (MMP) showed the highest differential expression in the microarray analysis, MMPs were further examined by in situ zymography and immunohistochemistry. Data were analyzed using one-way ANOVA followed by Tukey test. Results We observed that cysts and granulomas differentially expressed several ECM molecules, especially those from the matrix metalloproteinase (MMP) family. Compared to cysts, granulomas exhibited higher MMP enzymatic activity in areas stained for MMP-9. These areas were composed of polymorphonuclear cells (PMNs), in contrast to cysts. Similarly, MMP-13 was expressed by a greater number of cells in granulomas compared to cysts. Conclusion Our findings indicate that high enzymatic MMP activity in PMNs together with MMP-9 and MMP-13 stained cells could be a molecular signature of granulomas, unlike periapical cysts. PMID:19720222

  10. Electrochemical Proteolytic Beacon for Detection of Matrix Metalloproteinase Activities

    SciTech Connect

    Liu, Guodong; Wang, Jun; Wunschel, David S.; Lin, Yuehe

    2006-09-27

    This communication describes a novel method for detecting of matrix metalloproteinase-7 activity using a peptide substrate labeled with a ferrocene reporter. The substrate serves as a selective ‘electrochemical proteolytic beacon’ (EPB) for this metalloproteinase. The EPB is immobilized on a gold electrode surface to enable ‘on-off’ electrochemical signaling capability for uncleaved and cleaved events. The EPB is efficiently and selectively cleaved by MMP-7 as measured by the rate of decrease in redox current of ferrocene. Direct transduction of a signal corresponding to peptide cleavage events into an electronic signal thus provides a simple, sensitive route for detecting the MMP activity. The new method allows for identification of the activity of MMP-7 in concentrations as low as 3.4 pM. The concept can be extended to design multiple peptide substrate labeled with different electroactive reporters for assaying multiple MMPs activities.

  11. Electrochemical proteolytic beacon for detection of matrix metalloproteinase activities.

    PubMed

    Liu, Guodong; Wang, Jun; Wunschel, David S; Lin, Yuehe

    2006-09-27

    This communication describes a novel method for detecting matrix metalloproteinase-7 activity using a peptide substrate labeled with a ferrocene reporter. The substrate serves as a selective "electrochemical proteolytic beacon" (EPB) for this metalloproteinase. The EPB is immobilized on a gold electrode surface to enable "on-off" electrochemical signaling capability for uncleaved and cleaved events. The EPB is efficiently and selectively cleaved by MMP-7 as measured by the rate of decrease in redox current of ferrocene. Direct transduction of a signal corresponding to peptide cleavage events into an electronic signal thus provides a simple, sensitive route for detecting the MMP activity. The new method allows for identification of the activity of MMP-7 in concentrations as low as 3.4 pM. The concept can be extended to design a multiple peptide substrate labeled with different electroactive reporters for assaying multiple MMPs activities.

  12. Thin film transistor circuits for active matrix liquid crystal displays

    NASA Astrophysics Data System (ADS)

    Edwards, Martin John

    The demand for a high quality flat panel video display device for use in consumer and professional products has led to the rapid development of Active Matrix Liquid Crystal Displays (AMLCD). The majority of these displays use Thin Film Transistors (TFTs) as the active devices and improvements in the performance of these transistors is creating the opportunity to integrate increasingly sophisticated circuits onto the glass substrates of the displays. This thesis describes a number of aspects of the use of thin film transistor circuits for active matrix liquid crystal displays. The electrical characteristics of TFTs differ in a number of respects from those of conventional MOS devices. This is illustrated with measurements of transistors and simple circuits fabricated using two different low temperature poly-Si TFT technologies. At present the key application for TFT circuits is integration of the row and column drive circuits for active matrix liquid crystal displays. The issues which arise in the design of TFT drive circuits are discussed and the design and operation of a prototype display with integrated drive circuits is described. The availability of high mobility TFTs makes it possible to integrate signal processing functions within the pixels of a display. A novel technique employing digital to analogue conversion of the video data within the pixels of a display is presented. This technique allows the display to be addressed with digital column drive waveforms simplifying the column drive circuit. Operation of the pixel data converters has been demonstrated by the design and measurement of small arrays of test pixels.

  13. Laminated active matrix organic light-emitting devices

    NASA Astrophysics Data System (ADS)

    Liu, Hongyu; Sun, Runguang

    2008-02-01

    Laminated active matrix organic light-emitting device (AMOLED) realizing top emission by using bottom-emitting organic light-emitting diode (OLED) structure was proposed. The multilayer structure of OLED deposited in the conventional sequence is not on the thin film transistor (TFT) backplane but on the OLED plane. The contact between the indium tin oxide (ITO) electrode of TFT backplane and metal cathode of OLED plane is implemented by using transfer electrode. The stringent pixel design for aperture ratio of the bottom-emitting AMOLED, as well as special technology for the top ITO electrode of top-emitting AMOLED, is unnecessary in the laminated AMOLED.

  14. Heterogeneity of serum activities of matrix metalloproteinases in chronic endometritis.

    PubMed

    Sukhikh, G T; Soboleva, G M; Silantyeva, E S; Shagerbieva, E A; Serov, V N

    2007-04-01

    Matrix metalloproteinases belong to the key molecules of tissue remodeling involved in physiological and pathological processes of the female reproductive system. Adequate levels of their expression in the endometrium are essential for effective implantation and uneventful pregnancy. Chronic inflammatory process in the endometrium is associated with low tissue expression of metalloproteinase-9. Histologically verified chronic endometritis is associated with low serum activities of metalloproteinases 2 and 9, which are restored after combined etiotropic therapy. We measured serum levels of metalloproteinases in patients with chronic endometritis concomitant with sterility and its changes during the first days after magnetotherapy. PMID:18214304

  15. Lumican: a new inhibitor of matrix metalloproteinase-14 activity.

    PubMed

    Pietraszek, Katarzyna; Chatron-Colliet, Aurore; Brézillon, Stéphane; Perreau, Corinne; Jakubiak-Augustyn, Anna; Krotkiewski, Hubert; Maquart, François-Xavier; Wegrowski, Yanusz

    2014-11-28

    We previously showed that lumican regulates MMP-14 expression. The aim of this study was to compare the effect of lumican and decorin on MMP-14 activity. In contrast to decorin, the glycosylated form of lumican was able to significantly decrease MMP-14 activity in B16F1 melanoma cells. Our results suggest that a direct interaction occurs between lumican and MMP-14. Lumican behaves as a competitive inhibitor which leads to a complete blocking of the activity of MMP-14. It binds to the catalytic domain of MMP-14 with moderate affinity (KD∼275 nM). Lumican may protect collagen against MMP-14 proteolysis, thus influencing cell-matrix interaction in tumor progression. PMID:25304424

  16. Modeling mechanophore activation within a crosslinked glassy matrix

    NASA Astrophysics Data System (ADS)

    Silberstein, Meredith N.; Min, Kyoungmin; Cremar, Lee D.; Degen, Cassandra M.; Martinez, Todd J.; Aluru, Narayana R.; White, Scott R.; Sottos, Nancy R.

    2013-07-01

    Mechanically induced reactivity is a promising means for designing self-reporting materials. Mechanically sensitive chemical groups called mechanophores are covalently linked into polymers in order to trigger specific chemical reactions upon mechanical loading. These mechanophores can be linked either within the backbone or as crosslinks between backbone segments. Mechanophore response is sensitive to both the matrix properties and placement within the matrix, providing two avenues for material design. A model framework is developed to describe reactivity of mechanophores located as crosslinks in a glassy polymer matrix. Simulations are conducted at the molecular and macromolecular scales in order to develop macroscale constitutive relations. The model is developed specifically for the case of spiropyran (SP) in lightly crosslinked polymethylmethacrylate (PMMA). This optically trackable mechanophore (fluorescent when activated) allows the model to be assessed in terms of observed experimental behavior. The force modified potential energy surface (FMPES) framework is used in conjunction with ab initio steered molecular dynamics (MD) simulations of SP to determine the mechanophore kinetics. MD simulations of the crosslinked PMMA structure under shear deformation are used to determine the relationship between macroscale stress and local force on the crosslinks. A continuum model implemented in a finite element framework synthesizes these mechanochemical relations with the mechanical behavior. The continuum model with parameters taken directly from the FMPES and MD analyses under predicts stress-driven activation relative to experimental data. The continuum model, with the physically motivated modification of force fluctuations, provides an accurate prediction for monotonic loading across three decades of strain rate and creep loading, suggesting that the fundamental physics are captured.

  17. Matrix metalloproteinase-1 inhibitory activity of Kaempferia pandurata Roxb.

    PubMed

    Shim, Jae-Seok; Choi, Eun-Jung; Lee, Chan-Woo; Kim, Han-Sung; Hwang, Jae-Kwan

    2009-06-01

    Matrix metalloproteinase (MMP)-1 is a superfamily of zinc-dependent endopeptidases that are capable of degrading all components of the extracellular matrix. Kaempferia pandurata extract (0.01-0.5 microg/mL) significantly reduced the expression of MMP-1 and induced the expression of type 1 procollagen at the protein and mRNA levels in a dose-dependent manner. Ultraviolet (UV)-induced MMP-1 initiates cleavage of fibrillar collagen. Once cleaved by MMP-1, collagen can be further degraded by elevated levels of MMP-3 and MMP-9. It was found that increased MMP-1 expression due to UV irradiation was mediated by activation of mitogen-activated protein kinases such as extracellular-regulated kinase (ERK), Jun N-terminal kinase (JNK), and p38 kinase. Treatment of K. pandurata extract in the range of 0.01-0.5 microg/mL inhibited the UV-induced phosphorylations of ERK, JNK, and p38, respectively. Moreover, inhibition of phosphorylated ERK, JNK, and p38 by K. pandurata extract resulted in decreased c-Fos expression and c-Jun phosphorylation induced by UV light. The results strongly suggest that K. pandurata is potentially useful for the prevention and treatment of skin aging.

  18. Residual matrix from different separation techniques impacts exosome biological activity

    PubMed Central

    Paolini, Lucia; Zendrini, Andrea; Noto, Giuseppe Di; Busatto, Sara; Lottini, Elisabetta; Radeghieri, Annalisa; Dossi, Alessandra; Caneschi, Andrea; Ricotta, Doris; Bergese, Paolo

    2016-01-01

    Exosomes are gaining a prominent role in research due to their intriguing biology and several therapeutic opportunities. However, their accurate purification from body fluids and detailed physicochemical characterization remain open issues. We isolated exosomes from serum of patients with Multiple Myeloma by four of the most popular purification methods and assessed the presence of residual contaminants in the preparations through an ad hoc combination of biochemical and biophysical techniques - including Western Blot, colloidal nanoplasmonics, atomic force microscopy (AFM) and scanning helium ion microscopy (HIM). The preparations obtained by iodixanol and sucrose gradients were highly pure. To the contrary, those achieved with limited processing (serial centrifugation or one step precipitation kit) resulted contaminated by a residual matrix, embedding the exosomes. The contaminated preparations showed lower ability to induce NfkB nuclear translocation in endothelial cells with respect to the pure ones, probably because the matrix prevents the interaction and fusion of the exosomes with the cell membrane. These findings suggest that exosome preparation purity must be carefully assessed since it may interfere with exosome biological activity. Contaminants can be reliably probed only by an integrated characterization approach aimed at both the molecular and the colloidal length scales. PMID:27009329

  19. Calcium-Oxidant Signaling Network Regulates AMP-activated Protein Kinase (AMPK) Activation upon Matrix Deprivation*

    PubMed Central

    Sundararaman, Ananthalakshmy; Amirtham, Usha; Rangarajan, Annapoorni

    2016-01-01

    The AMP-activated protein kinase (AMPK) has recently been implicated in anoikis resistance. However, the molecular mechanisms that activate AMPK upon matrix detachment remain unexplored. In this study, we show that AMPK activation is a rapid and sustained phenomenon upon matrix deprivation, whereas re-attachment to the matrix leads to its dephosphorylation and inactivation. Because matrix detachment leads to loss of integrin signaling, we investigated whether integrin signaling negatively regulates AMPK activation. However, modulation of focal adhesion kinase or Src, the major downstream components of integrin signaling, failed to cause a corresponding change in AMPK signaling. Further investigations revealed that the upstream AMPK kinases liver kinase B1 (LKB1) and Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ) contribute to AMPK activation upon detachment. In LKB1-deficient cells, we found AMPK activation to be predominantly dependent on CaMKKβ. We observed no change in ATP levels under detached conditions at early time points suggesting that rapid AMPK activation upon detachment was not triggered by energy stress. We demonstrate that matrix deprivation leads to a spike in intracellular calcium as well as oxidant signaling, and both these intracellular messengers contribute to rapid AMPK activation upon detachment. We further show that endoplasmic reticulum calcium release-induced store-operated calcium entry contributes to intracellular calcium increase, leading to reactive oxygen species production, and AMPK activation. We additionally show that the LKB1/CaMKK-AMPK axis and intracellular calcium levels play a critical role in anchorage-independent cancer sphere formation. Thus, the Ca2+/reactive oxygen species-triggered LKB1/CaMKK-AMPK signaling cascade may provide a quick, adaptable switch to promote survival of metastasizing cancer cells. PMID:27226623

  20. Monolithic Active Pixel Matrix with Binary Counters (MAMBO) ASIC

    SciTech Connect

    Khalid, Farah F.; Deptuch, Grzegorz; Shenai, Alpana; Yarema, Raymond J.; /Fermilab

    2010-11-01

    Monolithic Active Matrix with Binary Counters (MAMBO) is a counting ASIC designed for detecting and measuring low energy X-rays from 6-12 keV. Each pixel contains analogue functionality implemented with a charge preamplifier, CR-RC{sup 2} shaper and a baseline restorer. It also contains a window comparator which can be trimmed by 4 bit DACs to remove systematic offsets. The hits are registered by a 12 bit ripple counter which is reconfigured as a shift register to serially output the data from the entire ASIC. Each pixel can be tested individually. Two diverse approaches have been used to prevent coupling between the detector and electronics in MAMBO III and MAMBO IV. MAMBO III is a 3D ASIC, the bottom ASIC consists of diodes which are connected to the top ASIC using {mu}-bump bonds. The detector is decoupled from the electronics by physically separating them on two tiers and using several metal layers as a shield. MAMBO IV is a monolithic structure which uses a nested well approach to isolate the detector from the electronics. The ASICs are being fabricated using the SOI 0.2 {micro}m OKI process, MAMBO III is 3D bonded at T-Micro and MAMBO IV nested well structure was developed in collaboration between OKI and Fermilab.

  1. Collagenolytic Matrix Metalloproteinase Activities toward Peptomeric Triple-Helical Substrates.

    PubMed

    Stawikowski, Maciej J; Stawikowska, Roma; Fields, Gregg B

    2015-05-19

    Although collagenolytic matrix metalloproteinases (MMPs) possess common domain organizations, there are subtle differences in their processing of collagenous triple-helical substrates. In this study, we have incorporated peptoid residues into collagen model triple-helical peptides and examined MMP activities toward these peptomeric chimeras. Several different peptoid residues were incorporated into triple-helical substrates at subsites P3, P1, P1', and P10' individually or in combination, and the effects of the peptoid residues were evaluated on the activities of full-length MMP-1, MMP-8, MMP-13, and MMP-14/MT1-MMP. Most peptomers showed little discrimination between MMPs. However, a peptomer containing N-methyl Gly (sarcosine) in the P1' subsite and N-isobutyl Gly (NLeu) in the P10' subsite was hydrolyzed efficiently only by MMP-13 [nomenclature relative to the α1(I)772-786 sequence]. Cleavage site analysis showed hydrolysis at the Gly-Gln bond, indicating a shifted binding of the triple helix compared to the parent sequence. Favorable hydrolysis by MMP-13 was not due to sequence specificity or instability of the substrate triple helix but rather was based on the specific interactions of the P7' peptoid residue with the MMP-13 hemopexin-like domain. A fluorescence resonance energy transfer triple-helical peptomer was constructed and found to be readily processed by MMP-13, not cleaved by MMP-1 and MMP-8, and weakly hydrolyzed by MT1-MMP. The influence of the triple-helical structure containing peptoid residues on the interaction between MMP subsites and individual substrate residues may provide additional information about the mechanism of collagenolysis, the understanding of collagen specificity, and the design of selective MMP probes.

  2. Active matrix metalloproteinase-7 is associated with invasion in buccal squamous cell carcinoma.

    PubMed

    Chuang, Hui-Ching; Su, Chih-Ying; Huang, Hsuang-Ying; Huang, Chao-Cheng; Chien, Chih-Yen; Du, Yung-Ying; Chuang, Jiin-Haur

    2008-12-01

    Protein microarrays have shown that matrix metalloproteinase-7 is upregulated in head and neck squamous cell carcinomas, but its role in local tissue invasion is still uncertain. We investigated the expression of active matrix metalloproteinase-7, using tissue microarray, immunohistochemistry, and western blotting, in oral tissues from 24 patients with buccal squamous cell carcinoma, and correlated the findings with clinicopathological features. Normal buccal tissue samples from the same patients, obtained at sites at least 1 cm from tumor tissue, served as normal controls. Total matrix metalloproteinase-7 was detected on western blots in 9 of 15 (60%) tumor tissue samples and in 2 of 15 (13%) normal mucosal samples; this difference was significant (P=0.008). Moreover, the active matrix metalloproteinase-7 was expressed only in eight of the nine (89%) tumor samples that expressed matrix metalloproteinase-7, and in none of the normal tissue samples, regardless of the expression status of the pro-matrix metalloproteinase-7. Immunostaining of matrix metalloproteinase-7 was observed histologically in both tumor and nonneoplastic epithelium, but immunostaining of active matrix metalloproteinase-7 was present only in tumor nests. Expression of active matrix metalloproteinase-7 was associated with larger tumor size (P=0.022) and was significantly higher in buccal squamous cell carcinoma with adjacent skin or bone invasion (P=0.036). In conclusion, active matrix metalloproteinase-7 expression was associated with more aggressive buccal squamous cell carcinomas. PMID:18931651

  3. Coupling a DNA-Based Machine with Glucometer Readouts for Amplified Detection of Telomerase Activity in Cancer Cells

    PubMed Central

    Wang, Wenjing; Huang, Shan; Li, Jingjing; Rui, Kai; Zhang, Jian-Rong; Zhu, Jun-Jie

    2016-01-01

    The strong correlation between cancer and telomerase activity has inspired the development of new strategies to evaluate telomerase activity. Here, a personal glucose meter (PGM) system that uses DNA-based machine amplification to detect telomerase in cancer cells is reported. In this assay, telomerase elongation products are amplified in the form of another type of product by a DNA-based machine. This process can only be activated by the hybridization of the extended telomerase substrate (TS) probe and the complementary primer in the presence of telomerase. The obtained products are then transformed to glucose-related signals via a three-component assay, which enables the simple use of a PGM to indirectly quantify the telomerase activity. The proposed method realizes sensitive telomerase activity detection down to 20 HeLa cells with a significantly enhanced dynamic range. Additionally, short telomerase elongation products, such as telomerase substrate probes with two repetitive sequences, that cannot be detected using the most widely used telomeric repeat amplification protocol assay were detected. PMID:27009555

  4. Medipix2 parallel readout system

    NASA Astrophysics Data System (ADS)

    Fanti, V.; Marzeddu, R.; Randaccio, P.

    2003-08-01

    A fast parallel readout system based on a PCI board has been developed in the framework of the Medipix collaboration. The readout electronics consists of two boards: the motherboard directly interfacing the Medipix2 chip, and the PCI board with digital I/O ports 32 bits wide. The device driver and readout software have been developed at low level in Assembler to allow fast data transfer and image reconstruction. The parallel readout permits a transfer rate up to 64 Mbytes/s. http://medipix.web.cern ch/MEDIPIX/

  5. Active Matrix Organic Light Emitting Diode (AMOLED) Environmental Test Report

    NASA Technical Reports Server (NTRS)

    Salazar, George A.

    2013-01-01

    This report focuses on the limited environmental testing of the AMOLED display performed as an engineering evaluation by The NASA Johnson Space Center (JSC)-specifically. EMI. Thermal Vac, and radiation tests. The AMOLED display is an active-matrix Organic Light Emitting Diode (OLED) technology. The testing provided an initial understanding of the technology and its suitability for space applications. Relative to light emitting diode (LED) displays or liquid crystal displays (LCDs), AMOLED displays provide a superior viewing experience even though they are much lighter and smaller, produce higher contrast ratio and richer colors, and require less power to operate than LCDs. However, AMOLED technology has not been demonstrated in a space environment. Therefore, some risks with the technology must be addressed before they can be seriously considered for human spaceflight. The environmental tests provided preliminary performance data on the ability of the display technology to handle some of the simulated induced space/spacecraft environments that an AMOLED display will see during a spacecraft certification test program. This engineering evaluation is part of a Space Act Agreement (SM) between The NASA/JSC and Honeywell International (HI) as a collaborative effort to evaluate the potential use of AMOLED technology for future human spaceflight missions- both government-led and commercial. Under this SM, HI is responsible for doing optical performance evaluation, as well as temperature and touch screen studies. The NASA/JSC is responsible for performing environmental testing comprised of EMI, Thermal Vac, and radiation tests. Additionally, as part of the testing, limited optical data was acquired to assess performance as the display was subjected to the induced environments. The NASA will benefit from this engineering evaluation by understanding AMOLED suitability for future use in space as well as becoming a smarter buyer (or developer) of the technology. HI benefits

  6. Automatic readout micrometer

    DOEpatents

    Lauritzen, T.

    A measuring system is described for surveying and very accurately positioning objects with respect to a reference line. A principle use of this surveying system is for accurately aligning the electromagnets which direct a particle beam emitted from a particle accelerator. Prior art surveying systems require highly skilled surveyors. Prior art systems include, for example, optical surveying systems which are susceptible to operator reading errors, and celestial navigation-type surveying systems, with their inherent complexities. The present invention provides an automatic readout micrometer which can very accurately measure distances. The invention has a simplicity of operation which practically eliminates the possibilities of operator optical reading error, owning to the elimination of traditional optical alignments for making measurements. The invention has an extendable arm which carries a laser surveying target. The extendable arm can be continuously positioned over its entire length of travel by either a coarse of fine adjustment without having the fine adjustment outrun the coarse adjustment until a reference laser beam is centered on the target as indicated by a digital readout. The length of the micrometer can then be accurately and automatically read by a computer and compared with a standardized set of alignment measurements. Due to its construction, the micrometer eliminates any errors due to temperature changes when the system is operated within a standard operating temperature range.

  7. Automatic readout micrometer

    DOEpatents

    Lauritzen, Ted

    1982-01-01

    A measuring system is disclosed for surveying and very accurately positioning objects with respect to a reference line. A principal use of this surveying system is for accurately aligning the electromagnets which direct a particle beam emitted from a particle accelerator. Prior art surveying systems require highly skilled surveyors. Prior art systems include, for example, optical surveying systems which are susceptible to operator reading errors, and celestial navigation-type surveying systems, with their inherent complexities. The present invention provides an automatic readout micrometer which can very accurately measure distances. The invention has a simplicity of operation which practically eliminates the possibilities of operator optical reading error, owning to the elimination of traditional optical alignments for making measurements. The invention has an extendable arm which carries a laser surveying target. The extendable arm can be continuously positioned over its entire length of travel by either a coarse or fine adjustment without having the fine adjustment outrun the coarse adjustment until a reference laser beam is centered on the target as indicated by a digital readout. The length of the micrometer can then be accurately and automatically read by a computer and compared with a standardized set of alignment measurements. Due to its construction, the micrometer eliminates any errors due to temperature changes when the system is operated within a standard operating temperature range.

  8. SNO+ Readout Electronics Upgrades

    NASA Astrophysics Data System (ADS)

    Bonventre, Richard; Shokair, Timothy; Knapik, Robert

    2012-03-01

    The SNO+ experiment is designed to explore several topics in neutrino physics including neutrinoless double beta decay, reactor antineutrinos, and low energy solar neutrinos. SNO+ uses the existing Sudbury Neutrino Observatory (SNO) detector, with the heavy water target replaced with liquid scintillator. The new target requires an upgrade to the command and control electronics to handle the higher rates expected with scintillation light as compared to Cherenkov light. The readout electronics have been upgraded to autonomously push data to a central data acquisition computer over ethernet from each of the 19 front end crates. The autonomous readout is achieved with a field programmable gate array (FPGA) with an embedded processor. Inside the FPGA fabric a state machine is configured to pull data across the VME-like bus of each crate. A small C program, making use of the open source Light Weight IP (LWIP) libraries, is run directly on the hardware (with no operating system) to push the data via TCP/IP. The hybrid combination of `high-level' C code and a `low-level' VHDL state machine is a cost effective and flexible solution for reading out individual front end crates.

  9. Millisecond readout CCD camera

    NASA Astrophysics Data System (ADS)

    Prokop, Mark; McCurnin, Thomas W.; Stradling, Gary L.

    1993-01-01

    We have developed a prototype of a fast-scanning CCD readout system to record a 1024 X 256 pixel image and transport the image to a recording station within 1 ms of the experimental event. The system is designed to have a dynamic range of greater than 1000 with adequate sensitivity to read single-electron excitations of a CRT phosphor when amplified by a microchannel plate image intensifier. This readout camera is intended for recording images from oscilloscopes, streak, and framing cameras. The sensor is a custom CCD chip, designed by LORAL Aeroneutronics. This CCD chip is designed with 16 parallel output ports to supply the necessary image transfer speed. The CCD is designed as an interline structure to allow fast clearing of the image and on-chip fast sputtering. Special antiblooming provisions are also included. The camera is designed to be modular and to allow CCD chips of other sizes to be used with minimal reengineering of the camera head.

  10. Millisecond readout CCD camera

    NASA Astrophysics Data System (ADS)

    Prokop, M.; McCurnin, T. W.; Stradling, G.

    We have developed a prototype of a fast-scanning CCD readout system to record a 1024 x 256 pixel image and transport the image to a recording station within 1 ms of the experimental event. The system is designed to have a dynamic range of greater than 1000 with adequate sensitivity to read single-electron excitations of a CRT phosphor when amplified by a microchannel plate image intensifier. This readout camera is intended for recording images from oscilloscopes, streak, and framing cameras. The sensor is a custom CCD chip, designed by LORAL Aeroneutronics. This CCD chip is designed with 16 parallel output ports to supply the necessary image transfer speed. The CCD is designed as an interline structure to allow fast clearing of the image and on-chip fast shuttering. Special antiblooming provisions are also included. The camera is designed to be modular and to allow CCD chips of other sizes to be used with minimal reengineering of the camera head.

  11. Readout of the upgraded ALICE-ITS

    NASA Astrophysics Data System (ADS)

    Szczepankiewicz, A.

    2016-07-01

    The ALICE experiment will undergo a major upgrade during the second long shutdown of the CERN LHC. As part of this program, the present Inner Tracking System (ITS), which employs different layers of hybrid pixels, silicon drift and strip detectors, will be replaced by a completely new tracker composed of seven layers of monolithic active pixel sensors. The upgraded ITS will have more than twelve billion pixels in total, producing 300 Gbit/s of data when tracking 50 kHz Pb-Pb events. Two families of pixel chips realized with the TowerJazz CMOS imaging process have been developed as candidate sensors: the ALPIDE, which uses a proprietary readout and sparsification mechanism and the MISTRAL-O, based on a proven rolling shutter architecture. Both chips can operate in continuous mode, with the ALPIDE also supporting triggered operations. As the communication IP blocks are shared among the two chip families, it has been possible to develop a common Readout Electronics. All the sensor components (analog stages, state machines, buffers, FIFOs, etc.) have been modelled in a system level simulation, which has been extensively used to optimize both the sensor and the whole readout chain design in an iterative process. This contribution covers the progress of the R&D efforts and the overall expected performance of the ALICE-ITS readout system.

  12. Matrix viscoplasticity and its shielding by active mechanics in microtissue models: experiments and mathematical modeling

    NASA Astrophysics Data System (ADS)

    Liu, Alan S.; Wang, Hailong; Copeland, Craig R.; Chen, Christopher S.; Shenoy, Vivek B.; Reich, Daniel H.

    2016-09-01

    The biomechanical behavior of tissues under mechanical stimulation is critically important to physiological function. We report a combined experimental and modeling study of bioengineered 3D smooth muscle microtissues that reveals a previously unappreciated interaction between active cell mechanics and the viscoplastic properties of the extracellular matrix. The microtissues’ response to stretch/unstretch actuations, as probed by microcantilever force sensors, was dominated by cellular actomyosin dynamics. However, cell lysis revealed a viscoplastic response of the underlying model collagen/fibrin matrix. A model coupling Hill-type actomyosin dynamics with a plastic perfectly viscoplastic description of the matrix quantitatively accounts for the microtissue dynamics, including notably the cells’ shielding of the matrix plasticity. Stretch measurements of single cells confirmed the active cell dynamics, and were well described by a single-cell version of our model. These results reveal the need for new focus on matrix plasticity and its interactions with active cell mechanics in describing tissue dynamics.

  13. Matrix viscoplasticity and its shielding by active mechanics in microtissue models: experiments and mathematical modeling

    PubMed Central

    Liu, Alan S.; Wang, Hailong; Copeland, Craig R.; Chen, Christopher S.; Shenoy, Vivek B.; Reich, Daniel H.

    2016-01-01

    The biomechanical behavior of tissues under mechanical stimulation is critically important to physiological function. We report a combined experimental and modeling study of bioengineered 3D smooth muscle microtissues that reveals a previously unappreciated interaction between active cell mechanics and the viscoplastic properties of the extracellular matrix. The microtissues’ response to stretch/unstretch actuations, as probed by microcantilever force sensors, was dominated by cellular actomyosin dynamics. However, cell lysis revealed a viscoplastic response of the underlying model collagen/fibrin matrix. A model coupling Hill-type actomyosin dynamics with a plastic perfectly viscoplastic description of the matrix quantitatively accounts for the microtissue dynamics, including notably the cells’ shielding of the matrix plasticity. Stretch measurements of single cells confirmed the active cell dynamics, and were well described by a single-cell version of our model. These results reveal the need for new focus on matrix plasticity and its interactions with active cell mechanics in describing tissue dynamics. PMID:27671239

  14. Compensated digital readout family

    NASA Technical Reports Server (NTRS)

    Ludwig, David E.; Skow, Michael

    1991-01-01

    ISC has completed test on an IC which has 32 channels of amplifiers, low pass anti-aliasing filters, 13-bit analog-to-digital (A/D) converters with non-uniformity correction per channel and a digital multiplexer. The single slope class of A/D conversion is described, as are the unique variations required for incorporation of this technique for use with on-focal plane detector readout electronics. This paper describes the architecture used to implement the digital on-focal plane signal processing functions. Results from measured data on a test IC are presented for a circuit containing these functions operating at a sensor frame rate of 1000 hertz.

  15. Follow-up: Prospective compound design using the 'SAR Matrix' method and matrix-derived conditional probabilities of activity.

    PubMed

    Gupta-Ostermann, Disha; Hirose, Yoichiro; Odagami, Takenao; Kouji, Hiroyuki; Bajorath, Jürgen

    2015-01-01

    In a previous Method Article, we have presented the 'Structure-Activity Relationship (SAR) Matrix' (SARM) approach. The SARM methodology is designed to systematically extract structurally related compound series from screening or chemical optimization data and organize these series and associated SAR information in matrices reminiscent of R-group tables. SARM calculations also yield many virtual candidate compounds that form a "chemical space envelope" around related series. To further extend the SARM approach, different methods are developed to predict the activity of virtual compounds. In this follow-up contribution, we describe an activity prediction method that derives conditional probabilities of activity from SARMs and report representative results of first prospective applications of this approach. PMID:25949808

  16. Protease induced plasticity: matrix metalloproteinase-1 promotes neurostructural changes through activation of protease activated receptor 1

    PubMed Central

    Allen, Megan; Ghosh, Suhasini; Ahern, Gerard P.; Villapol, Sonia; Maguire-Zeiss, Kathleen A.; Conant, Katherine

    2016-01-01

    Matrix metalloproteinases (MMPs) are a family of secreted endopeptidases expressed by neurons and glia. Regulated MMP activity contributes to physiological synaptic plasticity, while dysregulated activity can stimulate injury. Disentangling the role individual MMPs play in synaptic plasticity is difficult due to overlapping structure and function as well as cell-type specific expression. Here, we develop a novel system to investigate the selective overexpression of a single MMP driven by GFAP expressing cells in vivo. We show that MMP-1 induces cellular and behavioral phenotypes consistent with enhanced signaling through the G-protein coupled protease activated receptor 1 (PAR1). Application of exogenous MMP-1, in vitro, stimulates PAR1 dependent increases in intracellular Ca2+ concentration and dendritic arborization. Overexpression of MMP-1, in vivo, increases dendritic complexity and induces biochemical and behavioral endpoints consistent with increased GPCR signaling. These data are exciting because we demonstrate that an astrocyte-derived protease can influence neuronal plasticity through an extracellular matrix independent mechanism. PMID:27762280

  17. Analytical Model of Water Flow in Coal with Active Matrix

    NASA Astrophysics Data System (ADS)

    Siemek, Jakub; Stopa, Jerzy

    2014-12-01

    This paper presents new analytical model of gas-water flow in coal seams in one dimension with emphasis on interactions between water flowing in cleats and coal matrix. Coal as a flowing system, can be viewed as a solid organic material consisting of two flow subsystems: a microporous matrix and a system of interconnected macropores and fractures. Most of gas is accumulated in the microporous matrix, where the primary flow mechanism is diffusion. Fractures and cleats existing in coal play an important role as a transportation system for macro scale flow of water and gas governed by Darcy's law. The coal matrix can imbibe water under capillary forces leading to exchange of mass between fractures and coal matrix. In this paper new partial differential equation for water saturation in fractures has been formulated, respecting mass exchange between coal matrix and fractures. Exact analytical solution has been obtained using the method of characteristics. The final solution has very simple form that may be useful for practical engineering calculations. It was observed that the rate of exchange of mass between the fractures and the coal matrix is governed by an expression which is analogous to the Newton cooling law known from theory of heat exchange, but in present case the mass transfer coefficient depends not only on coal and fluid properties but also on time and position. The constant term of mass transfer coefficient depends on relation between micro porosity and macro porosity of coal, capillary forces, and microporous structure of coal matrix. This term can be expressed theoretically or obtained experimentally. W artykule zaprezentowano nowy model matematyczny przepływu wody i gazu w jednowymiarowej warstwie węglowej z uwzględnieniem wymiany masy między systemem szczelin i matrycą węglową. Węgiel jako system przepływowy traktowany jest jako układ o podwójnej porowatości i przepuszczalności, składający się z mikroporowatej matrycy węglowej oraz z

  18. The fine grained detector readout electronics

    NASA Astrophysics Data System (ADS)

    Retière, F.; T2K/FGD Collaboration

    2010-11-01

    The Fine Grained Detector (FGD) readout electronics was designed to record a snapshot of the detector activity before, during and after the neutrino beam spill produced by the J-PARC accelerator complex in Tokai, Japan. The FGD is a key element of T2K near detector currently being constructed. It will act as an active target detecting charged particles produced within its scintillator bars. The original feature of the FGD electronics is to readout Multi-Pixel Photon Counters by recording waveforms using Switch Capacitor Array chips (AFTER ASIC) designed for T2K Time Projection Chamber. In these proceedings, we describe the architecture of the FGD electronics. Beam results show that the physics requirements are met or exceeded. The relatively slow sampling frequency of the AFTER ASIC does not impair the timing resolution significantly. In addition, the very good efficiency of the system for detecting Michel electrons produced by pions or muons decay has been demonstrated.

  19. Activity of matrix metalloproteinases during antimycobacterial therapy in mice with simulated tuberculous inflammation.

    PubMed

    Sumenkova, D V; Russkikh, G S; Poteryaeva, O N; Polyakov, L M; Panin, L E

    2013-05-01

    Matrix metalloproteinases are shown to be involved in the pathogenesis of tuberculosis inflammation. In the early stages of BCG-granuloma formation in mouse liver and lungs, the serum levels of matrix metalloproteinases 2 and 7 increased by 4.5 times and remained unchanged while the pathology developed. Antimycobacterial therapy with isoniazid reduced enzyme activity almost to the level of intact control. The decrease in activity of matrix metalloproteinases 2 and 7 that play the most prominent role in the development of destructive forms of tuberculosis is of great therapeutic importance.

  20. Activation of Matrix Metalloproteinase-3 is altered at the frog neuromuscular junction following changes in synaptic activity.

    PubMed

    VanSaun, M; Humburg, B C; Arnett, M G; Pence, M; Werle, M J

    2007-09-15

    The extracellular matrix surrounding the neuromuscular junction is a highly specialized and dynamic structure. Matrix Metalloproteinases are enzymes that sculpt the extracellular matrix. Since synaptic activity is critical to the structure and function of this synapse, we investigated whether changes in synaptic activity levels could alter the activity of Matrix Metalloproteinases at the neuromuscular junction. In particular, we focused on Matrix Metalloproteinase 3 (MMP3), since antibodies to MMP3 recognize molecules at the frog neuromuscular junction, and MMP3 cleaves a number of synaptic basal lamina molecules, including agrin. Here we show that the fluorogenic compound (M2300) can be used to perform in vivo proteolytic imaging of the frog neuromuscular junction to directly measure the activity state of MMP3. Application of this compound reveals that active MMP3 is concentrated at the normal frog neuromuscular junction, and is tightly associated with the terminal Schwann cell. Blocking presynaptic activity via denervation, or TTX nerve blockade, results in a decreased level of active MMP3 at the neuromuscular junction. The loss of active MMP3 at the neuromuscular junction in denervated muscles can result from decreased activation of pro-MMP3, or it could result from increased inhibition of MMP3. These results support the hypothesis that changes in synaptic activity can alter the level of active MMP3 at the neuromuscular junction. PMID:17525979

  1. Hodoscope readout system

    DOEpatents

    Lee, L.Y.

    1973-12-01

    A readout system has been provided for reading out a radiation multidetector device with a reduced number of signal sensors. A radiation hodoscope, such as an array of scintillation counters, multiwire proportional counter array, or a set of multidetectors which do not receive signals simultaneously, is divided into equal numbered groups. A first group of signal terminals is connected to the equal numbered groups of detectors so that a signal from any one of the detectors of a group will be fed to one of the first group of terminals. A second group of signal terminals is connected to the detector groups so that a signal from a particular numbered detector of each of the detector groups is connected to one of the second group of terminals. Both groups of signal terminals are, in turn, coupled to signal sensors so that when a signal is simultaneously observed in one of the first group of terminals and one of the second group of tenniinals the specific detector detecting a radiation event is determined. The sensors are arranged in such a manner that a binary code is developed from their outputs which can be stored in a digital storage means according to the location of the event in the multidetector device. (Official Gazette)

  2. ASTM and VAMAS activities in titanium matrix composites test methods development

    NASA Technical Reports Server (NTRS)

    Johnson, W. S.; Harmon, D. M.; Bartolotta, P. A.; Russ, S. M.

    1994-01-01

    Titanium matrix composites (TMC's) are being considered for a number of aerospace applications ranging from high performance engine components to airframe structures in areas that require high stiffness to weight ratios at temperatures up to 400 C. TMC's exhibit unique mechanical behavior due to fiber-matrix interface failures, matrix cracks bridged by fibers, thermo-viscoplastic behavior of the matrix at elevated temperatures, and the development of significant thermal residual stresses in the composite due to fabrication. Standard testing methodology must be developed to reflect the uniqueness of this type of material systems. The purpose of this paper is to review the current activities in ASTM and Versailles Project on Advanced Materials and Standards (VAMAS) that are directed toward the development of standard test methodology for titanium matrix composites.

  3. Characterization of Silicon Detector Readout Electronics

    SciTech Connect

    Jones, M.

    2015-07-22

    Configuration and calibration of the front-end electronics typical of many silicon detector configurations were investigated in a lab activity based on a pair of strip sensors interfaced with FSSR2 read-out chips and an FPGA. This simple hardware configuration, originally developed for a telescope at the Fermilab Test Beam Facility, was used to measure thresholds and noise on individual readout channels and to study the influence that different configurations of the front-end electronics had on the observed levels of noise in the system. An understanding of the calibration and operation of this small detector system provided an opportunity to explore the architecture of larger systems such as those currently in use at LHC experiments.

  4. pH-Sensitive Microparticles with Matrix-Dispersed Active Agent

    NASA Technical Reports Server (NTRS)

    Li, Wenyan (Inventor); Buhrow, Jerry W. (Inventor); Jolley, Scott T. (Inventor); Calle, Luz M. (Inventor)

    2014-01-01

    Methods to produce pH-sensitive microparticles that have an active agent dispersed in a polymer matrix have certain advantages over microcapsules with an active agent encapsulated in an interior compartment/core inside of a polymer wall. The current invention relates to pH-sensitive microparticles that have a corrosion-detecting or corrosion-inhibiting active agent or active agents dispersed within a polymer matrix of the microparticles. The pH-sensitive microparticles can be used in various coating compositions on metal objects for corrosion detecting and/or inhibiting.

  5. Matrix Rigidity Activates Wnt Signaling through Down-regulation of Dickkopf-1 Protein*

    PubMed Central

    Barbolina, Maria V.; Liu, Yiuying; Gurler, Hilal; Kim, Mijung; Kajdacsy-Balla, Andre A.; Rooper, Lisa; Shepard, Jaclyn; Weiss, Michael; Shea, Lonnie D.; Penzes, Peter; Ravosa, Matthew J.; Stack, M. Sharon

    2013-01-01

    Cells respond to changes in the physical properties of the extracellular matrix with altered behavior and gene expression, highlighting the important role of the microenvironment in the regulation of cell function. In the current study, culture of epithelial ovarian cancer cells on three-dimensional collagen I gels led to a dramatic down-regulation of the Wnt signaling inhibitor dickkopf-1 with a concomitant increase in nuclear β-catenin and enhanced β-catenin/Tcf/Lef transcriptional activity. Increased three-dimensional collagen gel invasion was accompanied by transcriptional up-regulation of the membrane-tethered collagenase membrane type 1 matrix metalloproteinase, and an inverse relationship between dickkopf-1 and membrane type 1 matrix metalloproteinase was observed in human epithelial ovarian cancer specimens. Similar results were obtained in other tissue-invasive cells such as vascular endothelial cells, suggesting a novel mechanism for functional coupling of matrix adhesion with Wnt signaling. PMID:23152495

  6. A low power readout circuit approach for uncooled resistive microbolometer FPAs

    NASA Astrophysics Data System (ADS)

    Tepegoz, Murat; Toprak, Alperen; Akin, Tayfun

    2008-04-01

    This paper presents a new, low power readout circuit approach for uncooled resistive microbolometer FPAs. The readout circuits of the microbolometer detectors contain parallel readout channels whose outputs are driven and multiplexed on large bus capacitances in order to form the output of the readout circuit. High number of opamps used in the readout channel array and large output capacitances that these opamps should drive necessitates the use of high output current capacity structures, which results in large power dissipation. This paper proposes two new methods in order to decrease the power dissipation of the readout circuits for uncooled thermal FPAs. The first method is called the readout channel group concept, where the readout channel array is separated into groups in order to decrease the load capacitance seen by the readout channel output. The second method utilizes a special opamp architecture where the output current driving capacity can be digitally controlled. This method enables efficient use of power by activating the high output current driving capacity only during the output multiplexing. The simulations show that using these methods results in a power dissipation reduction of 80% and 91% for the readout channels optimized for a single output 384x288 FPA operating at 25 fps and for a two-output 640x480 FPA operating at 30 fps, respectively.

  7. Responsibility modulates pain-matrix activation elicited by the expressions of others in pain.

    PubMed

    Cui, Fang; Abdelgabar, Abdel-Rahman; Keysers, Christian; Gazzola, Valeria

    2015-07-01

    Here we examine whether brain responses to dynamic facial expressions of pain are influenced by our responsibility for the observed pain. Participants played a flanker task with a confederate. Whenever either erred, the confederate was seen to receive a noxious shock. Using functional magnetic resonance imaging, we found that regions of the functionally localized pain-matrix of the participants (the anterior insula in particular) were activated most strongly when seeing the confederate receive a noxious shock when only the participant had erred (and hence had full responsibility). When both or only the confederate had erred (i.e. participant's shared or no responsibility), significantly weaker vicarious pain-matrix activations were measured.

  8. Energy-recycling pixel for active-matrix organic light-emitting diode display

    NASA Astrophysics Data System (ADS)

    Yang, Che-Yu; Cho, Ting-Yi; Chen, Yen-Yu; Yang, Chih-Jen; Meng, Chao-Yu; Yang, Chieh-Hung; Yang, Po-Chuan; Chang, Hsu-Yu; Hsueh, Chun-Yuan; Wu, Chung-Chih; Lee, Si-Chen

    2007-06-01

    The authors report a pixel structure for active-matrix organic light-emitting diode (OLED) displays that has a hydrogenated amorphous silicon solar cell inserted between the driving polycrystalline Si thin-film transistor and the pixel OLED. Such an active-matrix OLED pixel structure not only exhibits a reduced reflection (and thus improved contrast) compared to conventional OLEDs but also is capable of recycling both incident photon energies and internally generated OLED radiation. Such a feature of energy recycling may be of use for portable/mobile electronics, which are particularly power aware.

  9. Linear readout of object manifolds

    NASA Astrophysics Data System (ADS)

    Chung, SueYeon; Lee, Daniel D.; Sompolinsky, Haim

    2016-06-01

    Objects are represented in sensory systems by continuous manifolds due to sensitivity of neuronal responses to changes in physical features such as location, orientation, and intensity. What makes certain sensory representations better suited for invariant decoding of objects by downstream networks? We present a theory that characterizes the ability of a linear readout network, the perceptron, to classify objects from variable neural responses. We show how the readout perceptron capacity depends on the dimensionality, size, and shape of the object manifolds in its input neural representation.

  10. Timepix3: a 65K channel hybrid pixel readout chip with simultaneous ToA/ToT and sparse readout

    NASA Astrophysics Data System (ADS)

    Poikela, T.; Plosila, J.; Westerlund, T.; Campbell, M.; De Gaspari, M.; Llopart, X.; Gromov, V.; Kluit, R.; van Beuzekom, M.; Zappon, F.; Zivkovic, V.; Brezina, C.; Desch, K.; Fu, Y.; Kruth, A.

    2014-05-01

    The Timepix3, hybrid pixel detector (HPD) readout chip, a successor to the Timepix \\cite{timepix2007} chip, can record time-of-arrival (ToA) and time-over-threshold (ToT) simultaneously in each pixel. ToA information is recorded in a 14-bit register at 40 MHz and can be refined by a further 4 bits with a nominal resolution of 1.5625 ns (640 MHz). ToT is recorded in a 10-bit overflow controlled counter at 40 MHz. Pixels can be programmed to record 14 bits of integral ToT and 10 bits of event counting, both at 40 MHz. The chip is designed in 130 nm CMOS and contains 256 × 256 pixel channels (55 × 55 μm2). The chip, which has more than 170 M transistors, has been conceived as a general-purpose readout chip for HPDs used in a wide range of applications. Common requirements of these applications are operation without a trigger signal, and sparse readout where only pixels containing event information are read out. A new architecture has been designed for sparse readout and can achieve a throughput of up to 40 Mhits/s/cm2. The flexible architecture offers readout schemes ranging from serial (one link) readout (40 Mbps) to faster parallel (up to 8 links) readout of 5.12 Gbps. In the ToA/ToT operation mode, readout is simultaneous with data acquisition thus keeping pixels sensitive at all times. The pixel matrix is formed by super pixel (SP) structures of 2 × 4 pixels. This optimizes resources by sharing the pixel readout logic which transports data from SPs to End-of-Column (EoC) using a 2-phase handshake protocol. To reduce power consumption in applications with a low duty cycle, an on-chip power pulsing scheme has been implemented. The logic switches bias currents of the analog front-ends in a sequential manner, and all front-ends can be switched in 800 ns. The digital design uses a mixture of commercial and custom standard cell libraries and was verified using Open Verification Methodology (OVM) and commercial timing analysis tools. The analog front-end and a

  11. Matrix fibronectin disruption and altered endothelial cell adhesion induced by activated leukocytes

    SciTech Connect

    Vincent, P.; Richards, P.; Saba, T.; DelVecchio, P.

    1986-03-01

    Sequestration of activated leukocytes (PMN) within the lung may contribute to pulmonary vascular injury following trauma, sepsis, or intravascular coagulation. Monolayers of cultured rat endothelial cells were utilized to evaluate the effect of activated PMNs on endothelial cell attachment and the extracellular fibronectin matrix over a 4 hr incubation interval. Rat endothelial cells were identified by immunofluorescent staining of Factor VIII R:Ag. Endothelial cells were labeled with /sup 51/Cr in order to establish a cell injury assay in which the release of pelletable (cell associated) or non-pelletable activity was measured in the media. PMN activation was verified by chemiluminescence activity. Following phorbol myristate acetate (PMA) the leukocytes aggregated, chemiluminesced, and caused detachment of /sup 51/Cr endothelial cells. Endothelial detachment increased as a function of time with a plateau by 3 hrs. Immunofluorescent analysis of extracellular fibronectin in endothelial cell cultures revealed disruption of the fibrillar matrix fibronectin in association with endothelial cell disadhesion. Matrix fibronectin disruption was not seen with PMNs or PMA alone. Thus, disruption of the fibronectin matrix by released proteases may contribute to endothelial cell detachment.

  12. Nobiletin metabolites: synthesis and inhibitory activity against matrix metalloproteinase-9 production.

    PubMed

    Oshitari, Tetsuta; Okuyama, Yuji; Miyata, Yoshiki; Kosano, Hiroshi; Takahashi, Hideyo; Natsugari, Hideaki

    2011-08-01

    A divergent synthesis of nobiletin metabolites was developed through highly oxygenated acetophenone derivative. We used commercially available methyl 3,4,5-trimethoxybenzoate as a starting material for concise preparation of the key intermediate, 2'-hydroxy-3',4',5',6'-tetramethoxyacetophenone (I). These metabolites showed strong inhibitory activity against matrix metalloproteinase-9 production in human lens epithelial cells.

  13. Bacterial lipopolysaccharides induce in vitro degradation of cartilage matrix through chondrocyte activation.

    PubMed

    Jasin, H E

    1983-12-01

    The present studies demonstrate that bacterial lipopolysaccharides (LPS) induce cartilage matrix degradation in live explants in organ culture. Quintuplicate bovine nasal fibrocartilage explants cultured for 8 d with three different purified LPS preparations derived from Escherichia coli and Salmonella typhosa at concentrations ranging from 1.0 to 25.0 micrograms/ml resulted in matrix proteoglycan depletion of 33.3 +/- 5.8 to 92.5 +/- 2.0% (medium control depletion 17.7 +/- 0.7 to 32.4 +/- 1.4%). Matrix degradation depended on the presence of live chondrocytes because frozen-thawed explants incubated with LPS failed to show any proteoglycan release. Moreover, the addition of Polymyxin B (25 micrograms/ml) to live explants incubated with LPS abolished matrix release, whereas Polymyxin B had no effect on the matrix-degrading activity provided by blood mononuclear cell factors. A highly purified Lipid A preparation induced matrix degradation at a concentration of 0.01 micrograms/ml. Cartilage matrix collagen and proteoglycan depletion also occurred with porcine articular cartilage explants (collagen release: 18.3 +/- 3.5%, medium control: 2.1 +/- 0.5%; proteoglycan release: 79.0 +/- 5.9%, medium control: 28.8 +/- 4.8%). Histochemical analysis of the cultured explants confirmed the results described above. Gel chromatography of the proteoglycans released in culture indicated that LPS induced significant degradation of the high molecular weight chondroitin sulfate-containing aggregates. These findings suggest that bacterial products may induce cartilage damage by direct stimulation of chondrocytes. This pathogenic mechanism may play a role in joint damage in septic arthritis and in arthropathies resulting from the presence of bacterial products derived from the gastrointestinal tract.

  14. Activity-based labeling of matrix metalloproteinases in living vertebrate embryos.

    PubMed

    Keow, Jonathan Y; Pond, Eric D; Cisar, Justin S; Cravatt, Benjamin F; Crawford, Bryan D

    2012-01-01

    Extracellular matrix (ECM) remodeling is a physiologically and developmentally essential process mediated by a family of zinc-dependent extracellular proteases called matrix metalloproteinases (MMPs). In addition to complex transcriptional control, MMPs are subject to extensive post-translational regulation. Because of this, classical biochemical, molecular and histological techniques that detect the expression of specific gene products provide useful but limited data regarding the biologically relevant activity of MMPs. Using benzophenone-bearing hydroxamate-based probes that interact with the catalytic zinc ion in MMPs, active proteases can be covalently 'tagged' by UV cross-linking. This approach has been successfully used to tag MMP-2 in vitro in tissue culture supernatants, and we show here that this probe tags proteins with mobilities consistent with known MMPs and detectable gelatinolytic activity in homogenates of zebrafish embryos. Furthermore, because of the transparency of the zebrafish embryo, UV-photocroslinking can be accomplished in vivo, and rhodamated benzophenone probe is detected in striking spatial patterns consistent with known distributions of active matrix remodeling in embryos. Finally, in metamorphosing Xenopus tadpoles, this probe can be used to biotinylate active MMP-2 by injecting it and cross-linking it in vivo, allowing the protein to be subsequently extracted and biochemically identified. PMID:22952682

  15. Synovial fluid matrix metalloproteinase-2 and -9 activities in dogs suffering from joint disorders

    PubMed Central

    MURAKAMI, Kohei; MAEDA, Shingo; YONEZAWA, Tomohiro; MATSUKI, Naoaki

    2016-01-01

    The activity of matrix metalloproteinase (MMP)-2 and MMP-9 in synovial fluids (SF) sampled from dogs with joint disorders was investigated by gelatin zymography and densitometry. Pro-MMP-2 showed similar activity levels in dogs with idiopathic polyarthritis (IPA; n=17) or canine rheumatoid arthritis (cRA; n=4), and healthy controls (n=10). However, dogs with cranial cruciate ligament rupture (CCLR; n=5) presented significantly higher pro-MMP-2 activity than IPA and healthy dogs. Meanwhile, dogs with IPA exhibited significantly higher activity of pro- and active MMP-9 than other groups. Activity levels in pro- and active MMP-9 in cRA and CCLR dogs were not significantly different from those in healthy controls. Different patterns of MMP-2 and MMP-9 activity may reflect the differences in the underlying pathological processes. PMID:26902805

  16. Angiostatin inhibits endothelial and melanoma cellular invasion by blocking matrix-enhanced plasminogen activation.

    PubMed Central

    Stack, M S; Gately, S; Bafetti, L M; Enghild, J J; Soff, G A

    1999-01-01

    Angiostatin, a kringle-containing fragment of plasminogen, is a potent inhibitor of angiogenesis. The mechanism(s) responsible for the anti-angiogenic properties of angiostatin are unknown. We now report that human angiostatin blocks plasmin(ogen)-enhanced in vitro invasion of tissue plasminogen activator (t-PA)-producing endothelial and melanoma cells. Kinetic analyses demonstrated that angiostatin functions as a non-competitive inhibitor of extracellular-matrix (ECM)-enhanced, t-PA-catalysed plasminogen activation, with a Ki of 0.9+/-0.03 microM. This mechanism suggests that t-PA has a binding site for the inhibitor angiostatin, as well as for its substrate plasminogen that, when occupied, prevents ternary complex formation between t-PA, plasminogen and matrix protein. Direct binding experiments confirmed that angiostatin bound to t-PA with an apparent Kd [Kd(app)] of 6.7+/-0.7 nM, but did not bind with high affinity to ECM proteins. Together, these data suggest that angiostatin in the cellular micro-environment can inhibit matrix-enhanced plasminogen activation, resulting in reduced invasive activity, and suggest a biochemical mechanism whereby angiostatin-mediated regulation of plasmin formation could influence cellular migration and invasion. PMID:10229661

  17. Involvement of matrix metalloproteinase activity in hormone-induced mammary tumor regression.

    PubMed

    Simian, Marina; Molinolo, Alfredo; Lanari, Claudia

    2006-01-01

    Proteolytic activity and remodeling of the extracellular matrix are important players in tumor progression. However, to date the role of the extracellular matrix in tumor regression remains unresolved. To address this, we used a progesterone-dependent in vivo mouse mammary tumor line, C4-HD, which regresses in response to hormone therapy. Within the first 72 hours of treatment, massive apoptosis was accompanied by changes in the staining patterns of laminin and collagens I, III, and IV. We thus hypothesized that an increase in matrix metalloproteinase (MMP) activity could be involved in this process. This indeed was the case as the activities of MMP-2, -9, and -3 increased in regressing tumors, coinciding with the peak of apoptosis. Moreover, cell-cell interactions were disrupted during early hours of regression with E-cadherin levels reduced and fragmentation products detected during regression. Analysis of beta-catenin revealed that although total levels within the tissue did not change, this molecule switched from being involved in cell-cell adhesion in the growing tumor to being expressed in the reactive stroma during regression. Our data provide a novel role for proteolytic activity in tumor regression and question the underlying principle for using MMP inhibitors in cancer treatment. PMID:16400029

  18. Communication: Active space decomposition with multiple sites: Density matrix renormalization group algorithm

    SciTech Connect

    Parker, Shane M.; Shiozaki, Toru

    2014-12-07

    We extend the active space decomposition method, recently developed by us, to more than two active sites using the density matrix renormalization group algorithm. The fragment wave functions are described by complete or restricted active-space wave functions. Numerical results are shown on a benzene pentamer and a perylene diimide trimer. It is found that the truncation errors in our method decrease almost exponentially with respect to the number of renormalization states M, allowing for numerically exact calculations (to a few μE{sub h} or less) with M = 128 in both cases. This rapid convergence is because the renormalization steps are used only for the interfragment electron correlation.

  19. Activation of AMPK Prevents Monocrotaline-Induced Extracellular Matrix Remodeling of Pulmonary Artery

    PubMed Central

    Li, Shaojun; Han, Dong; Zhang, Yonghong; Xie, Xinming; Ke, Rui; Zhu, Yanting; Liu, Lu; Song, Yang; Yang, Lan; Li, Manxiang

    2016-01-01

    Background The current study was performed to investigate the effect of adenosine monophosphate (AMP) – activated protein kinase (AMPK) activation on the extracellular matrix (ECM) remodeling of pulmonary arteries in pulmonary arterial hypertension (PAH) and to address its potential mechanisms. Material/Methods PAH was induced by a single intraperitoneal injection of monocrotaline (MCT) into Sprague-Dawley rats. Metformin (MET) was administered to activate AMPK. Immunoblotting was used to determine the phosphorylation and expression of AMPK and expression of tissue inhibitor of metalloproteinase-1 (TIMP-1). Gelatin zymography was performed to determine the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9. Results Activation of AMPK by MET significantly reduced the right ventricle systolic pressure and the right ventricular hypertrophy in MCT-induced rat PAH model, and partially inhibited the ECM remodeling of pulmonary arteries. These effects were coupled with the decrease of MMP-2/9 activity and TIMP-1 expression. Conclusions This study suggests that activation of AMPK benefits PAH by inhibiting ECM remodeling of pulmonary arteries. Enhancing AMPK activity might have potential value in clinical treatment of PAH. PMID:26978596

  20. Urinary matrix metalloproteinase activities: biomarkers for plaque angiogenesis and nephropathy in diabetes.

    PubMed

    McKittrick, Ian B; Bogaert, Yolanda; Nadeau, Kristen; Snell-Bergeon, Janet; Hull, Amber; Jiang, Tao; Wang, Xiaoxin; Levi, Moshe; Moulton, Karen S

    2011-12-01

    Diabetic complications of nephropathy and accelerated atherosclerosis are associated with vascular remodeling and dysregulated angiogenesis. Matrix metalloproteinases (MMP) modify extracellular matrix during vascular remodeling and are excreted in urine of patients with vascular malformation or tumor angiogenesis. We hypothesized that urinary MMP activities would be sensitive biomarkers for vascular remodeling in diabetic complications. Activities of MMP-2, MMP-9, and its complex with neutrophil gelatinase-associated lipocalin (NGAL/MMP-9) were measured by substrate gel zymography in urine from nondiabetic (ND) and type 1 diabetic (T1D) rodents that were susceptible to both T1D-induced plaque angiogenesis and nephropathy, or nephropathy alone. Additionally, these urine activities were measured in ND and T1D adolescents. Urinary MMP-9, MMP-2, and NGAL/MMP-9 activities were increased and more prevalent in T1D compared with ND controls. Urinary MMP-2 activity was detected in mice with T1D-induced plaque neovascularization. In nephropathy models, urinary NGAL/MMP-9 and MMP-9 activities appeared before onset of albuminuria, whereas MMP-2 was absent or delayed. Finally, urinary MMP activities were increased in adolescents with early stages of T1D. Urinary MMP activities may be sensitive, noninvasive, and clinically useful biomarkers for predicting vascular remodeling in diabetic renal and vascular complications. PMID:21921021

  1. Urinary matrix metalloproteinase activities: biomarkers for plaque angiogenesis and nephropathy in diabetes

    PubMed Central

    McKittrick, Ian B.; Bogaert, Yolanda; Nadeau, Kristen; Snell-Bergeon, Janet; Hull, Amber; Jiang, Tao; Wang, Xiaoxin; Levi, Moshe

    2011-01-01

    Diabetic complications of nephropathy and accelerated atherosclerosis are associated with vascular remodeling and dysregulated angiogenesis. Matrix metalloproteinases (MMP) modify extracellular matrix during vascular remodeling and are excreted in urine of patients with vascular malformation or tumor angiogenesis. We hypothesized that urinary MMP activities would be sensitive biomarkers for vascular remodeling in diabetic complications. Activities of MMP-2, MMP-9, and its complex with neutrophil gelatinase-associated lipocalin (NGAL/MMP-9) were measured by substrate gel zymography in urine from nondiabetic (ND) and type 1 diabetic (T1D) rodents that were susceptible to both T1D-induced plaque angiogenesis and nephropathy, or nephropathy alone. Additionally, these urine activities were measured in ND and T1D adolescents. Urinary MMP-9, MMP-2, and NGAL/MMP-9 activities were increased and more prevalent in T1D compared with ND controls. Urinary MMP-2 activity was detected in mice with T1D-induced plaque neovascularization. In nephropathy models, urinary NGAL/MMP-9 and MMP-9 activities appeared before onset of albuminuria, whereas MMP-2 was absent or delayed. Finally, urinary MMP activities were increased in adolescents with early stages of T1D. Urinary MMP activities may be sensitive, noninvasive, and clinically useful biomarkers for predicting vascular remodeling in diabetic renal and vascular complications. PMID:21921021

  2. In vivo detecting matrix metalloproteinase (MMP) activity by a genetically engineered fluorescent probe

    NASA Astrophysics Data System (ADS)

    Yang, Jie; Zhang, Zhihong; Su, Ting; Luo, Qingming

    2007-02-01

    Degradation of the extracellular matrix (ECM) by matrix metalloproteinases (MMPs) enhances tumor invasion and metastasis. To monitor MMP activity, we constructed plasmid that encoded a fluorescent sensor DC, in which an MMP substrate site (MSS) is sandwiched between DsRed2 and ECFP. MMPs are secretory proteins, only acting on the outside of cells; hence, an expressing vector was used that displayed the fluorescent sensor on the cellular surface. The DC was expressed in cells with high secretory MMP, so MSS was cleaved by MMP. Also, GM6001, an MMP inhibitor, causes DsRed2 signals to increase in living cells and on the chick embryo chorioallantoic membrane (CAM). Thus, this fluorescent sensor was able to sensitively monitor MMP activation in vivo. Potential applications for this sensor include high-throughput screening for MMP inhibitors for anti-cancer research, and detailed analysis of the effects of MMP inhibitors.

  3. Proton Channel Activity of Influenza A Virus Matrix Protein 2 Contributes to Autophagy Arrest

    PubMed Central

    Ren, Yizhong; Feng, Liqiang; Pan, Weiqi; Li, Liang; Wang, Qian; Li, Jiashun; Li, Na; Han, Ling; Zheng, Xuehua; Niu, Xuefeng; Sun, Caijun

    2015-01-01

    Influenza A virus infection can arrest autophagy, as evidenced by autophagosome accumulation in infected cells. Here, we report that this autophagosome accumulation can be inhibited by amantadine, an antiviral proton channel inhibitor, in amantadine-sensitive virus infected cells or cells expressing influenza A virus matrix protein 2 (M2). Thus, M2 proton channel activity plays a role in blocking the fusion of autophagosomes with lysosomes, which might be a key mechanism for arresting autophagy. PMID:26468520

  4. Implementation of advanced matrix corrections for active interrogation of waste drums using the CTEN instrument

    SciTech Connect

    Melton, S.; Estep, R.; Hollas, C.

    1998-12-31

    The combined thermal/epithermal neutron instrument (CTEN) was designed at Los Alamos to improve measurement accuracy and mitigate self shielding effects inherent in the differential dieaway technique (DDT). A major goal in this research effort has been the development of a calibration technique that incorporates recently developed matrix and self-shielding corrections using data generated from additional detectors and new acquisition techniques. A comprehensive data set containing both active and passive measurements was generated using 26 different matrices and comprising a total of 1,400 measurements. In all, 31 flux-and-matrix-dependent parameters, 24 positional parameters, two dieaway times, and a correlated ratio were determined from each of the over 1,400 measurements. A reduced list of matrix indicators, prioritized using the alternating conditional expectation (ACE) algorithm, was used to train a neural network using a generalized regression technique (GRNN) to determine matrix- and position-corrected calibration factors. This paper describes the experimental, analytical, and empirical techniques used to determine the corrected calibration factor for an unknown waste drum. Results from a range of cases are compared with those obtained using a mobile DDT instrument and traditional DDT algorithms.

  5. Active-matrix organic light-emitting diode displays on flexible metal foil substrates

    NASA Astrophysics Data System (ADS)

    Chuang, Ta-Ko

    This dissertation presents the research efforts that deal with the development of polysilicon thin film transistors (TFTs) on stainless-steel-foil substrates, the implementation of high-resolution flexible active-matrix backplanes, and the integration of the flexible polysilicon TFT backplanes with polymer light-emitting diodes. This research investigated the preparation of the steel foil substrates, the fabrication of flexible polysilicon TFT backplanes and polymer light emitting diodes (PLEDs), and the encapsulation of the flexible Active Matrix Polymer Light Emitting Diode displays. The first successful integration of polysilicon TFT backplane with PLEDs onto light-weight, robust, and flexible stainless-steel-foil substrates is presented. A top-emitting, monochrome active-matrix polymer light-emitting diode (AM-PLED) display, having the VGA (640x480) format and a 230 dpi resolution, is demonstrated for the first time on flexible stainless-steel-foil substrates. This work validates the compatibility of the polysilicon technology for high-resolution flexible AM-PLED displays. Furthermore, this work shows that a variety of other large-area microelectronics could also be implemented onto flexible metal foils, benefiting by the metal oil dimensional stability and ability to withstand high process temperature. In conclusion, the polysilicon TFT technology combining with metal-foil substrates opens up a new road for flexible displays as well as large-area flexible electronic applications.

  6. Matrix stiffness modulates formation and activity of neuronal networks of controlled architectures.

    PubMed

    Lantoine, Joséphine; Grevesse, Thomas; Villers, Agnès; Delhaye, Geoffrey; Mestdagh, Camille; Versaevel, Marie; Mohammed, Danahe; Bruyère, Céline; Alaimo, Laura; Lacour, Stéphanie P; Ris, Laurence; Gabriele, Sylvain

    2016-05-01

    The ability to construct easily in vitro networks of primary neurons organized with imposed topologies is required for neural tissue engineering as well as for the development of neuronal interfaces with desirable characteristics. However, accumulating evidence suggests that the mechanical properties of the culture matrix can modulate important neuronal functions such as growth, extension, branching and activity. Here we designed robust and reproducible laminin-polylysine grid micropatterns on cell culture substrates that have similar biochemical properties but a 100-fold difference in Young's modulus to investigate the role of the matrix rigidity on the formation and activity of cortical neuronal networks. We found that cell bodies of primary cortical neurons gradually accumulate in circular islands, whereas axonal extensions spread on linear tracks to connect circular islands. Our findings indicate that migration of cortical neurons is enhanced on soft substrates, leading to a faster formation of neuronal networks. Furthermore, the pre-synaptic density was two times higher on stiff substrates and consistently the number of action potentials and miniature synaptic currents was enhanced on stiff substrates. Taken together, our results provide compelling evidence to indicate that matrix stiffness is a key parameter to modulate the growth dynamics, synaptic density and electrophysiological activity of cortical neuronal networks, thus providing useful information on scaffold design for neural tissue engineering.

  7. The quartz hazard: effects of surface and matrix on inflammogenic activity.

    PubMed

    Donaldson, K; Stone, V; Duffin, R; Clouter, A; Schins, R; Borm, P

    2001-01-01

    Modification of the quartz surface during the history of the particle is a powerful idea in understanding the variability of the quartz hazard. Interactions between quartz and other minerals are likely to occur in sediments, during industrial processing, or in matrix-bound quartz. We discuss new evidence regarding the basis of changes in the quartz surface that relate to changes in its ability to cause inflammation. Different samples of quartz were subjected to various biological assays. Endpoints included instillation of quartz into the tracheobronchial tree and measurement of PMN numbers in bronchoalveolar lavage (BAL) and in lung tissue, levels of the chemokine MIP-2 in BAL, and nuclear translocation of the transcription factor NF-kappaB in BAL cells. In vitro biological assays included cytotoxicity to epithelial cells, hemolytic activity, and radical activity of the particle surface as measured by electron spin resonance. Treatment of quartz with aluminium lactate impaired its ability to cause PMN recruitment, chemokine release, and NF-kappaB nuclear translocation in BAL. Workplace quartzes had no proinflammatory activity, which correlated with their ability to cause hemolysis but not their electron spin resonance (ESR) activity. Quartz in a matrix with coalmine dust or fly-ash showed different effects. In fly-ash, the toxicity was masked, but coalmine dusts were more toxic to epithelial cells than pure quartz in vitro; however, after instillation, the long-term inflammation was not related to the in vitro activity. Amelioration of quartz surface activity can occur in workplace samples of quartz and quartz samples whose surface is protected, to the extent that they have very little inflammogenic activity and display an inability to activate key subcellular pathways that lead to inflammation. Quartz from a workplace whose surface has been affected, or in a matrix such as coalmine dust or fly-ash, can have its toxicity modulated. These effects are due to minerals

  8. Matrix metalloproteinase expression and activity in trophoblast-decidual tissues at organogenesis in CF-1 mouse.

    PubMed

    Fontana, Vanina; Coll, Tamara A; Sobarzo, Cristian M A; Tito, Leticia Perez; Calvo, Juan Carlos; Cebral, Elisa

    2012-10-01

    During early placentation, matrix metalloproteinases (MMPs) play important roles in decidualization, trophoblast migration, invasion, angiogenesis, vascularization and extracellular matrix (ECM) remodeling of the endometrium. The aim of our study was to analyze the localization, distribution and differential expression of MMP-2 and -9 in the organogenic implantation site and to evaluate in vivo and in vitro decidual MMP-2 and -9 activities on day 10 of gestation in CF-1 mouse. Whole extracts for Western blotting of organogenic E10-decidua expressed MMP-2 and -9 isoforms. MMP-2 immunoreactivity was found in a granular and discrete pattern in ECM of mesometrial decidua (MD) near maternal blood vessels and slightly in non-decidualized endometrium (NDE). Immunoexpression of MMP-9 was also detected in NDE, in cytoplasm of decidual cells and ECM of vascular MD, in trophoblastic area and in growing antimesometrial deciduum. Gelatin zymography showed that MMP-9 activity was significantly lower in CM compared to the active form of direct (not cultured) and cultured decidua. The decidual active MMP-9 was significantly higher than the active MMP-2. These results show differential localization, protein expression and enzymatic activation of MMPs, suggesting specific roles for MMP-2 and MMP-9 in decidual and trophoblast tissues related to organogenic ECM remodeling and vascularization during early establishment of mouse placentation. PMID:22714107

  9. Direct measurement of matrix metalloproteinase activity in 3D cellular microenvironments using a fluorogenic peptide substrate

    PubMed Central

    Leight, Jennifer L.; Alge, Daniel L.; Maier, Andrew J.; Anseth, Kristi S.

    2014-01-01

    Incorporation of degradable moieties into synthetic hydrogels has greatly increased the utility of these three-dimensional matrices for in vitro cell culture as well as tissue engineering applications. A common method for introducing degradability is the inclusion of oligopeptides sensitive to cleavage by matrix metalloproteinases (MMPs), enabling cell-mediated remodeling and migration within the material. While this strategy has been effective, characterization and measurement of cell-mediated degradation in these materials has remained challenging. There are 20+ MMP family members whose activity is regulated in space and time by a number of biochemical and biophysical cues. Thus, the typical approach of characterizing cleavage of degradable moieties in solution with recombinant enzymes does not easily translate to three dimensional cell-mediated matrix remodeling. To address this challenge, we report here the synthesis of a cell-laden hydrogel matrix functionalized with a fluorogenic peptide substrate to provide real-time, quantitative monitoring of global MMP activity. Using this system, stimulation of MMP activity was observed with growth factor treatment in mammary epithelial cells and compared to classical zymography results. Further, the effect of biophysical cues on MMP activity of human mesenchymal stem cells was also investigated where more rigid hydrogels were observed to increase MMP activity. The regulation of MMP activity by these biochemical and biophysical cues highlights the need for in situ, real time measurement of hydrogel degradation, and use of these functionalized hydrogels will aid in future rational design of degradable synthetic hydrogels for in vitro cell studies and tissue engineering applications. PMID:23830581

  10. Activation of matrix metalloproteinase-2 and -9 by 2- and 4-hydroxyestradiol.

    PubMed

    Paquette, Benoit; Bisson, Martine; Therriault, Hélène; Lemay, Rosalie; Paré, Mélanie; Banville, Pascale; Cantin, André M

    2003-10-01

    Breast cancer patients frequently develop metastases. This process requires the degradation of extracellular matrix proteins which act as a barrier to tumour cell passage. These proteins can be degraded by proteases, mainly the matrix metalloproteinases (MMPs). MMP-2 and -9 which are frequently detected in breast cancer tissues. ProMMPs are released from cancer cells, and their activation is considered to be a crucial step in metastases development. In breast cancer, estrogen metabolism is altered favouring the accumulation of 2- and 4-hydroxyestradiol (2- and 4-OHE(2)). These estradiol metabolites can generate free radicals. Since reactive species are known activators of proMMPs, this study was designed to determine if the free radicals generated by 2- and 4-OHE(2) can activate proMMP-2 and -9. Activation of MMPs by hydroxyestradiol was determined by monitoring the cleavage of a fluorogenic peptide and by zymography analysis. Both estradiol metabolites activated the MMP-2 and -9. 4-OHE(2) was a more potent activator than 2-OHE(2), which reflects its higher capacity to generate free radicals. ProMMPs activation was mainly mediated through O(2)*-, although the free radical HO* also activated the proMMPs but to a lesser extent. ProMMPs activation was not observed with estrogens that cannot generate free radicals, i.e. estradiol, estrone, 2- and 4-methoxyestradiol, and 16alpha-hydroxyestrone. These results demonstrate that 2- and 4-OHE(2) at a concentration as low as 10(-8)M can activate the proMMP-2 and -9 and might play an important role in the invasion of breast cancer cells.

  11. Active compensation of wavefront aberrations by controllable heating of lens with electric film heater matrix.

    PubMed

    Chen, Hua; Hou, Lv; Zhou, Xinglin

    2016-08-20

    We present a new apparatus for active compensation of wavefront aberrations by controllable heating of a lens using a film heater matrix. The annular electric film heater matrix, comprising 24 individual heaters, is attached to the periphery of a lens. Utilizing the linear superposition, and wavefront change proportional to the heating energy properties induced by heating, a controllable wavefront can be defined by solving a linear function. The two properties of wavefront change of a lens have been confirmed through a specially designed experiment. The feasibility of the compensation method is validated by compensating the wavefront of a plate lens. The results show that the wavefront of the lens changes from 12.52 to 2.95 nm rms after compensation. With a more precise electric controlling board, better results could be achieved. PMID:27556982

  12. Synthesis of In-situ Aluminum Matrix Composite Using a New Activated Powder Injection Method

    NASA Astrophysics Data System (ADS)

    Maleki, A.; Meratian, M.; Niroumand, B.; Gupta, M.

    2008-12-01

    In the present study, in-situ Al matrix composites containing alumina particles were synthesized by a new method that involved injection of an activated powder mixture into the molten aluminum, which was subsequently squeeze cast to minimize its porosity. The activated powder mixture was prepared by milling of powders of commercially pure aluminum and zinc oxide for a predetermined time. Milling for 60 minutes led to optimum activation of the reactant powders. Such activation reduced the reaction temperature from above 1000 °C to about 640 °C. Microstructural characterization studies revealed the formation of submicron size alumina particles with near equiaxed morphology and good particle/matrix interface. The composite specimen synthesized using the activated powder injection (API) method exhibited higher hardness, greater yield and tensile strengths, and lower elongation when compared to the monolithic specimen of similar composition. This article places particular emphasis on explaining the uniqueness of the processing methodology used in this study for synthesis of in-situ Al/Al2O3 composites.

  13. The modulation of platelet adhesion and activation by chitosan through plasma and extracellular matrix proteins.

    PubMed

    Lord, Megan S; Cheng, Bill; McCarthy, Simon J; Jung, MoonSun; Whitelock, John M

    2011-10-01

    Chitosan has been shown to promote initial wound closure events to prevent blood loss. Platelet adhesion and activation are crucial early events in these processes after traumatic bleeding leading to thrombus formation. Platelet adhesion to chitosan was found to be enhanced in the presence of adsorbed plasma and extracellular matrix proteins and was found to be primarily mediated by α(IIb)β(3) integrins, while α(2)β(1) integrins were found to be involved in platelet adhesion to collagen and perlecan. Platelets were found to be activated by chitosan, as shown by an increase in the expression of α(IIb)β(3) integrins and P-selectin, while the extent of activation was modulated by the presence of proteins including perlecan and fibrinogen. Collagen-coated chitosan was found to activate platelets to the same extent as either chitosan or collagen alone. These data support the role of plasma and extracellular matrix proteins in promoting chitosan mediated platelet adhesion and activation supporting the hypothesis that chitosan promotes wound healing via these interactions.

  14. Small-Scale Readout Systems Prototype for the STAR PIXEL Detector

    SciTech Connect

    Szelezniak, Michal A.; Besson, Auguste; Colledani, Claude; Dorokhov, Andrei; Dulinski, Wojciech; Greiner, Leo C.; Himmi, Abdelkader; Hu, Christine; Matis, Howard S.; Ritter, Hans Georg; Rose, Andrew; Shabetai, Alexandre; Stezelberger, Thorsten; Sun, Xiangming; Thomas, Jim H.; Valin, Isabelle; Vu, Chinh Q.; Wieman, Howard H.; Winter, Marc

    2008-10-01

    A prototype readout system for the STAR PIXEL detector in the Heavy Flavor Tracker (HFT) vertex detector upgrade is presented. The PIXEL detector is a Monolithic Active Pixel Sensor (MAPS) based silicon pixel vertex detector fabricated in a commercial CMOS process that integrates the detector and front-end electronics layers in one silicon die. Two generations ofMAPS prototypes designed specifically for the PIXEL are discussed. We have constructed a prototype telescope system consisting of three small MAPS sensors arranged in three parallel and coaxial planes with a readout system based on the readout architecture for PIXEL. This proposed readout architecture is simple and scales to the size required to readout the final detector. The real-time hit finding algorithm necessary for data rate reduction in the 400 million pixel detector is described, and aspects of the PIXEL system integration into the existing STAR framework are addressed. The complete system has been recently tested and shown to be fully functional.

  15. A data readout approach for physics experiments

    NASA Astrophysics Data System (ADS)

    Huang, Xi-Ru; Cao, Ping; Gao, Li-Wei; Zheng, Jia-Jun

    2015-07-01

    With increasing physical event rates and the number of electronic channels, traditional readout schemes meet the challenge of improving readout speed caused by the limited bandwidth of the crate backplane. In this paper, a high-speed data readout method based on the Ethernet is presented to make each readout module capable of transmitting data to the DAQ. Features of explicitly parallel data transmitting and distributed network architecture give the readout system the advantage of adapting varying requirements of particle physics experiments. Furthermore, to guarantee the readout performance and flexibility, a standalone embedded CPU system is utilized for network protocol stack processing. To receive the customized data format and protocol from front-end electronics, a field programmable gate array (FPGA) is used for logic reconfiguration. To optimize the interface and to improve the data throughput between CPU and FPGA, a sophisticated method based on SRAM is presented in this paper. For the purpose of evaluating this high-speed readout method, a simplified readout module is designed and implemented. Test results show that this module can support up to 70 Mbps data throughput from the readout module to DAQ. Supported by National Natural Science Foundation of China (11005107) and Independent Projects of State Key Laboratory of Particle Detection and Electronics (201301)

  16. Nanosecond monolithic CMOS readout cell

    DOEpatents

    Souchkov, Vitali V.

    2004-08-24

    A pulse shaper is implemented in monolithic CMOS with a delay unit formed of a unity gain buffer. The shaper is formed of a difference amplifier having one input connected directly to an input signal and a second input connected to a delayed input signal through the buffer. An elementary cell is based on the pulse shaper and a timing circuit which gates the output of an integrator connected to the pulse shaper output. A detector readout system is formed of a plurality of elementary cells, each connected to a pixel of a pixel array, or to a microstrip of a plurality of microstrips, or to a detector segment.

  17. Aging enhances a mechanically-induced reduction in tendon strength by an active process involving matrix metalloproteinase activity.

    PubMed

    Dudhia, Jayesh; Scott, Charlotte M; Draper, Edward R C; Heinegård, Dick; Pitsillides, Andrew A; Smith, Roger K

    2007-08-01

    Age-associated and degenerative loss of functional integrity in soft tissues develops from effects of cumulative and subtle changes in their extracellular matrix (ECM). The highly ordered tendon ECM provides the tissue with its tensile strength during loading. As age and exercise collide in the high incidence of tendinopathies, we hypothesized that aged tendons fail due to cumulative damage resulting from a combination of diminished matrix repair and fragmentation of ECM proteins induced by prolonged cyclical loading, and that this is an active cell-mediated process. We developed an equine tendon explant model to examine the effect of age on the influence of prolonged cyclical loading at physiologically relevant strain rates (5% strain, 1 Hz for 24 h) on tissue mechanical properties, loss of ECM protein and matrix metalloproteinase (MMP) expression. We show significantly diminished mechanical strength of cyclically loaded tissue compared to controls (39.7 +/- 12%, P activity. Furthermore, tendon from older specimens was more susceptible to weakening (11-30 years, 50%P matrix protein, an integral ECM protein, an effect that could be mimicked by culture with fibronectin fragments. These findings indicate prolonged cyclical loading of physiological magnitude decreases tendon tensile strength by an active process, and that MMPs may contribute to loss of functional competence, exaggerated by age, via load-induced proteolytic disruption of the ECM.

  18. Distribution and activity levels of matrix metalloproteinase 2 and 9 in canine and feline osteosarcoma.

    PubMed

    Gebhard, Christiane; Fuchs-Baumgartinger, Andrea; Razzazi-Fazeli, Ebrahim; Miller, Ingrid; Walter, Ingrid

    2016-01-01

    Overexpression of matrix metalloproteinases (MMPs) has been associated with increased tumor aggressiveness and metastasis dissemination. We investigated whether the contrasting metastatic behavior of feline and canine osteosarcoma is related to levels and activities of MMP2 and MMP9. Zymography and immunohistochemistry were used to determine expression levels of MMP2 and MMP9 in canine and feline osteosarcoma. Using immunohistochemistry, increased MMP9 levels were identified in most canine osteosarcomas, whereas cat samples more often displayed moderate levels. High levels of pro-MMP9, pro-MMP2, and active MMP2 were detected by gelatin zymography in both species, with significantly higher values for active MMP2 in canine osteosarcoma. These findings indicate that MMP2 is probably involved in canine and feline osteosarcoma and their expression and activity could be associated with the different metastatic behavior of canine and feline osteosarcoma. PMID:26733734

  19. The parasite Entamoeba histolytica exploits the activities of human matrix metalloproteinases to invade colonic tissue.

    PubMed

    Thibeaux, Roman; Avé, Patrick; Bernier, Michèle; Morcelet, Marie; Frileux, Pascal; Guillén, Nancy; Labruyère, Elisabeth

    2014-10-07

    Intestinal invasion by the protozoan parasite Entamoeba histolytica is characterized by remodelling of the extracellular matrix (ECM). The parasite cysteine proteinase A5 (CP-A5) is thought to cooperate with human matrix metalloproteinases (MMPs) involved in ECM degradation. Here, we investigate the role CP-A5 plays in the regulation of MMPs upon mucosal invasion. We use human colon explants to determine whether CP-A5 activates human MMPs. Inhibition of the MMPs' proteolytic activities abolishes remodelling of the fibrillar collagen structure and prevents trophozoite invasion of the mucosa. In the presence of trophozoites, MMPs-1 and -3 are overexpressed and are associated with fibrillar collagen remodelling. In vitro, CP-A5 performs the catalytic cleavage needed to activate pro-MMP-3, which in turn activates pro-MMP-1. Ex vivo, incubation with recombinant CP-A5 was enough to rescue CP-A5-defective trophozoites. Our results suggest that MMP-3 and/or CP-A5 inhibitors may be of value in further studies aiming to treat intestinal amoebiasis.

  20. High frame rate measurements of semiconductor pixel detector readout IC

    NASA Astrophysics Data System (ADS)

    Szczygiel, R.; Grybos, P.; Maj, P.

    2012-07-01

    We report on high count rate and high frame rate measurements of a prototype IC named FPDR90, designed for readouts of hybrid pixel semiconductor detectors used for X-ray imaging applications. The FPDR90 is constructed in 90 nm CMOS technology and has dimensions of 4 mm×4 mm. Its main part is a matrix of 40×32 pixels with 100 μm×100 μm pixel size. The chip works in the single photon counting mode with two discriminators and two 16-bit ripple counters per pixel. The count rate per pixel depends on the effective CSA feedback resistance and can be set up to 6 Mcps. The FPDR90 can operate in the continuous readout mode, with zero dead time. Due to the architecture of digital blocks in pixel, one can select the number of bits read out from each counter from 1 to 16. Because in the FPDR90 prototype only one data output is available, the frame rate is 9 kfps and 72 kfps for 16 bits and 1 bit readout, respectively (with nominal clock frequency of 200 MHz).

  1. Lung Matrix Metalloproteinase Activation following Partial Hepatic Ischemia/Reperfusion Injury in Rats

    PubMed Central

    Ferrigno, Andrea; Rizzo, Vittoria; Tarantola, Eleonora

    2014-01-01

    Purpose. Warm hepatic ischemia-reperfusion (I/R) injury can lead to multiorgan dysfunction. The aim of the present study was to investigate whether acute liver I/R does affect the function and/or structure of remote organs such as lung, kidney, and heart via modulation of extracellular matrix remodelling. Methods. Male Sprague-Dawley rats were subjected to 30 min partial hepatic ischemia by clamping the hepatic artery and the portal vein. After a 60 min reperfusion, liver, lung, kidney, and heart biopsies and blood samples were collected. Serum hepatic enzymes, creatinine, urea, Troponin I and TNF-alpha, and tissue matrix metalloproteinases (MMP-2, MMP-9), myeloperoxidase (MPO), malondialdehyde (MDA), and morphology were monitored. Results. Serum levels of hepatic enzymes and TNF-alpha were concomitantly increased during hepatic I/R. An increase in hepatic MMP-2 and MMP-9 activities was substantiated by tissue morphology alterations. Notably, acute hepatic I/R affect the lung inasmuch as MMP-9 activity and MPO levels were increased. No difference in MMPs and MPO was observed in kidney and heart. Conclusions. Although the underlying mechanism needs further investigation, this is the first study in which the MMP activation in a distant organ is reported; this event is probably TNF-alpha-mediated and the lung appears as the first remote organ to be involved in hepatic I/R injury. PMID:24592193

  2. Phloroglucinol Reduces Photodamage in Hairless Mice via Matrix Metalloproteinase Activity Through MAPK Pathway.

    PubMed

    Im, A-Rang; Nam, Kung-Woo; Hyun, Jin Won; Chae, Sungwook

    2016-01-01

    We investigated the photoprotective activity of phloroglucinol on ultraviolet B (UVB)-induced deleterious effects in hairless mice in vivo. To assess the photoprotective effect of phloroglucinol, phloroglucinol-treated HR-1 hairless male mice were exposed to UVB irradiation. The inhibitory activity of phloroglucinol on wrinkle formation was determined by analysis of skin replicas, epidermal thickness based on histological examination and collagen damage. Matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase (TIMP) mRNA levels were measured by real-time PCR. UVB induced transcription of proinflammatory cytokines, including interleukin-1 beta (IL-1β, IL-6) and IL-8 (IL-8). The protective effects of phloroglucinol on UVB-induced skin photoaging were examined by measuring protein levels of MMPs and mitogen-activated protein (MAP) kinases. The results of these experiments suggest that phloroglucinol has a significant beneficial effect on the barrier function of the skin. In hairless mice, signs of photoaging and photodamage, including coarse wrinkle formation, epidermal thickness and elastic fiber degeneration, were reduced in severity by phloroglucinol application. The phloroglucinol-treated group showed remarkably decreased mRNA levels of MMP-1, MMP-9 and inflammatory cytokines in comparison with those of the UVB-induced group. Oral administration of phloroglucinol attenuated phosphorylation of MAP kinases, including extracellular signal-regulated kinase, c-Jun N-terminal kinase and p38. PMID:26537624

  3. Stimulation of Periodontal Ligament Stem Cells by Dentin Matrix Protein 1 Activates Mitogen-Activated Protein Kinase and Osteoblast Differentiation

    PubMed Central

    Chandrasekaran, Sangeetha; Ramachandran, Amsaveni; Eapen, Asha; George, Anne

    2013-01-01

    Background Periodontitis can ultimately result in tooth loss. Many natural and synthetic materials have been tried to achieve periodontal regeneration, but the results remain variable and unpredictable. We hypothesized that exogenous treatment with dentin matrix protein 1 (DMP1) activates specific genes and results in phenotypic and functional changes in human periodontal ligament stem cells (hPDLSCs). Methods hPDLSCs were isolated from extracted teeth and cultured in the presence or absence of DMP1. Quantitative polymerase chain reactions were performed to analyze the expression of several genes involved in periodontal regeneration. hPDLSCs were also processed for immunocytochemical and Western blot analysis using phosphorylated extracellular signal-regulated kinase (pERK) and ERK antibodies. Alkaline phosphatase and von Kossa staining were performed to characterize the differentiation of hPDLSCs into osteoblasts. Field emission scanning electron microscopic analysis of the treated and control cell cultures were also performed. Results Treatment with DMP1 resulted in the upregulation of genes, such as matrix metalloproteinase-2, alkaline phosphatase, and transforming growth factor β1. Activation of ERK mitogen-activated protein kinase signaling pathway and translocation of pERK from the cytoplasm to the nucleus was observed. Overall, DMP1-treated cells showed increased expression of alkaline phosphatase, increased matrix, and mineralized nodule formation when compared with untreated controls. Conclusion DMP1 can orchestrate a coordinated expression of genes and phenotypic changes in hPDLSCs by activation of the ERK signaling pathway, which may provide a valuable strategy for tissue engineering approaches in periodontal regeneration. PMID:22612367

  4. Matrix metalloproteinase and elastase activities in LPS-induced acute lung injury in guinea pigs.

    PubMed

    D'Ortho, M P; Jarreau, P H; Delacourt, C; Macquin-Mavier, I; Levame, M; Pezet, S; Harf, A; Lafuma, C

    1994-03-01

    Matrix metalloproteinases (MMPs) and elastase are proteolytic enzymes specifically directed against extracellular matrix (ECM) components. They are secreted by inflammatory cells and may consequently contribute to the lesions of the ECM observed during acute pulmonary edema. We therefore evaluated the MMP and elastase activities, which are secreted by cultured alveolar macrophages (AMACs) and polymorphonuclear neutrophils (PMNs) and present in the bronchoalveolar lavage (BAL) fluid in a guinea pig model of acute lung injury induced by intratracheal instillation of lipopolysaccharide (LPS). The control group was given 0.9% NaCl. 24 h after instillation, a BAL was performed, the BAL fluid was separated from the cells by centrifugation, and AMACs and PMNs were separately cultured for 24 h. In BAL fluid from LPS-treated guinea pigs, we found 1) an increase in free gelatinase activity, tested on [3H]gelatin (0.7 +/- 0.2 micrograms.200 microliters BAL fluid-1.48 h-1 vs. 0.2 +/- 0.1 in controls, P < 0.05), and 2) increased total gelatinase activities, as assessed by zymography. The molecular masses of the major gelatinase species found in BAL fluid by zymography were 92 and 68 kDa. The 92-kDa gelatinase was secreted by both AMACs and PMNs, as demonstrated by zymography of their respective culture media. When tested on [3H]elastin, the elastase activity of BAL fluid of LPS-treated animals exhibited no increase, but when tested on a synthetic peptidic substrate [N-succinyl-(L-alanine)3-p-nitro anilide (SLAPN)], increased elastase-like activity was observed (from 17 +/- 4 nmol of SLAPN.200 microliters BAL fluid-1.24 h-1 in control group to 34 +/- 8 in LPS group, P < 0.05). This increase was attributable to the activity of a metalloendopeptidase that was inhibited by the metal chelator EDTA but not by the specific tissue inhibitor of MMPs.

  5. Matrix metalloproteinase expression and activity following prostaglandin F(2 alpha)-induced luteolysis.

    PubMed

    Ricke, William A; Smith, George W; Smith, Michael F

    2002-03-01

    Luteal tissue contains matrix metalloproteinases (MMPs) that cleave specific components of the extracellular matrix (ECM) and are inhibited by tissue inhibitors of metalloproteinases (TIMPs). We previously reported a decrease in luteal TIMP-1 within 15 min of prostaglandin F(2 alpha) (PGF(2 alpha))-induced luteolysis. An increase in the MMP:TIMP ratio may promote ECM degradation and apoptosis, as observed in other tissues that undergo involution. The objectives of these experiments were to determine whether 1) PGF(2 alpha) affects expression of mRNA encoding fibrillar collagenases (MMP-1 and -13), gelatinases A and B (MMP-2 and -9), membrane type (mt)-1 MMP (MMP-14), stromelysin (MMP-3), and matrilysin (MMP-7), and 2) PGF(2 alpha) increases MMP activity during PGF(2 alpha)-induced luteolysis in sheep. Corpora lutea (n = 3-10/time point) were collected at 0, 15, and 30 min and 1, 2, 4, 6, 12, 24, and 48 h after PGF(2 alpha) administration. Northern blot analysis confirmed the presence of all MMPs except MMP-9. Expression of mRNA for the above MMPs (except MMP-2) increased significantly (P < 0.05) by 30 min, and all MMPs increased significantly (P < 0.05) by 6 h after PGF(2 alpha) administration. Expression of MMP-14 mRNA increased significantly (P < 0.05) by 15 min post-PGF(2 alpha) and remained elevated through 48 h. MMP activity in luteal homogenates (following proenzyme activation and inactivation of inhibitors) was increased significantly (P < 0.05) by 15 min and remained elevated through 48 h post-PGF(2 alpha). MMP activity was localized (in situ zymography) to the pericellular area of various cell types in the 0-h group and was markedly increased by 30 min post-PGF(2 alpha). MMP mRNA expression and activity were significantly increased following PGF(2 alpha) treatment. Increased MMP activity may promote ECM degradation during luteolysis.

  6. Collagen-binding VEGF mimetic peptide: Structure, matrix interaction, and endothelial cell activation

    NASA Astrophysics Data System (ADS)

    Chan, Tania R.

    Long term survival of artificial tissue constructs depends greatly on proper vascularization. In nature, differentiation of endothelial cells and formation of vasculature are directed by dynamic spatio-temporal cues in the extracellular matrix that are difficult to reproduce in vitro. In this dissertation, we present a novel bifunctional peptide that mimics matrix-bound vascular endothelial growth factor (VEGF), which can be used to encode spatially controlled angiogenic signals in collagen-based scaffolds. The peptide, QKCMP, contains a collagen mimetic domain (CMP) that binds to type I collagen by a unique triple helix hybridization mechanism and a VEGF mimetic domain (QK) with pro-angiogenic activity. We demonstrate QKCMP's ability to hybridize with native and heat denatured collagens through a series of binding studies on collagen and gelatin substrates. Circular dichroism experiments show that the peptide retains the triple helical structure vital for collagen binding, and surface plasmon resonance study confirms the molecular interaction between the peptide and collagen strands. Cell culture studies demonstrate QKCMP's ability to induce endothelial cell morphogenesis and network formation as a matrix-bound factor in 2D and 3D collagen scaffolds. We also show that the peptide can be used to spatially modify collagen-based substrates to promote localized endothelial cell activation and network formation. To probe the biological events that govern these angiogenic cellular responses, we investigated the cell signaling pathways activated by collagen-bound QKCMP and determined short and long-term endothelial cell response profiles for p38, ERK1/2, and Akt signal transduction cascades. Finally, we present our efforts to translate the peptide's in vitro bioactivity to an in vivo burn injury animal model. When implanted at the wound site, QKCMP functionalized biodegradable hydrogels induce enhanced neovascularization in the granulation tissue. The results show QKCMP

  7. THE DIFFERENTIAL REGULATION OF CELL MOTILE ACTIVITY THROUGH MATRIX STIFFNESS AND POROSITY IN THREE DIMENSIONAL COLLAGEN MATRICES

    PubMed Central

    Miron-Mendoza, Miguel; Seemann, Joachim; Grinnell, Frederick

    2010-01-01

    In three dimensional collagen matrices, cell motile activity results in collagen translocation, cell spreading and cell migration. Cells can penetrate into the matrix as well as spread and migrate along its surface. In the current studies, we quantitatively characterize collagen translocation, cell spreading and cell migration in relationship to collagen matrix stiffness and porosity. Collagen matrices prepared with 1 to 4 mg/ml collagen exhibited matrix stiffness (storage modulus measured by oscillating rheometry) increasing from 4 to 60 Pa and matrix porosity (measured by scanning electron microscopy) decreasing from 4 to 1 μm2. Over this collagen concentration range, the consequences of cell motile activity changed markedly. As collagen concentration increased, cells no longer were able to cause translocation of collagen fibrils. Cell migration increased and cell spreading changed from dendritic to more flattened and polarized morphology depending on location of cells within or on the surface of the matrix. Collagen translocation appeared to depend primarily on matrix stiffness, whereas cell spreading and migration were less dependent on matrix stiffness and more dependent on collagen matrix porosity. PMID:20537378

  8. Report of the sensor readout electronics panel

    NASA Technical Reports Server (NTRS)

    Fossum, Eric R.; Carson, J.; Kleinhans, W.; Kosonocky, W.; Kozlowski, L.; Pecsalski, A.; Silver, A.; Spieler, H.; Woolaway, J.

    1991-01-01

    The findings of the Sensor Readout Electronics Panel are summarized in regard to technology assessment and recommended development plans. In addition to two specific readout issues, cryogenic readouts and sub-electron noise, the panel considered three advanced technology areas that impact the ability to achieve large format sensor arrays. These are mega-pixel focal plane packaging issues, focal plane to data processing module interfaces, and event driven readout architectures. Development in each of these five areas was judged to have significant impact in enabling the sensor performance desired for the Astrotech 21 mission set. Other readout issues, such as focal plane signal processing or other high volume data acquisition applications important for Eos-type mapping, were determined not to be relevant for astrophysics science goals.

  9. Chromium liquid waste inertization in an inorganic alkali activated matrix: leaching and NMR multinuclear approach.

    PubMed

    Ponzoni, Chiara; Lancellotti, Isabella; Barbieri, Luisa; Spinella, Alberto; Saladino, Maria Luisa; Martino, Delia Chillura; Caponetti, Eugenio; Armetta, Francesco; Leonelli, Cristina

    2015-04-01

    A class of inorganic binders, also known as geopolymers, can be obtained by alkali activation of aluminosilicate powders at room temperature. The process is affected by many parameters (curing time, curing temperature, relative humidity etc.) and leads to a resistant matrix usable for inertization of hazardous waste. In this study an industrial liquid waste containing a high amount of chromium (≈ 2.3 wt%) in the form of metalorganic salts is inertized into a metakaolin based geopolymer matrix. One of the innovative aspects is the exploitation of the water contained in the waste for the geopolymerization process. This avoided any drying treatment, a common step in the management of liquid hazardous waste. The evolution of the process--from the precursor dissolution to the final geopolymer matrix hardening--of different geopolymers containing a waste amount ranging from 3 to 20%wt and their capability to inertize chromium cations were studied by: i) the leaching tests, according to the EN 12,457 regulation, at different curing times (15, 28, 90 and 540 days) monitoring releases of chromium ions (Cr(III) and Cr(VI)) and the cations constituting the aluminosilicate matrix (Na, Si, Al); ii) the humidity variation for different curing times (15 and 540 days); iii) SEM characterization at different curing times (28 and 540 days); iv) the trend of the solution conductivity and pH during the leaching test; v) the characterization of the short-range ordering in terms of TOT bonds (where T is Al or Si) by (29)Si and (27)Al solid state magic-angle spinning nuclear magnetic resonance (ss MAS NMR) for geopolymers containing high amounts of waste (10-20%wt). The results show the formation of a stable matrix after only 15 days independently on the waste amount introduced; the longer curing times increase the matrices stabilities and their ability to immobilize chromium cations. The maximum amount of waste that can be inertized is around 10 wt% after a curing time of 28 days.

  10. High-Sensitivity X-ray Polarimetry with Amorphous Silicon Active-Matrix Pixel Proportional Counters

    NASA Technical Reports Server (NTRS)

    Black, J. K.; Deines-Jones, P.; Jahoda, K.; Ready, S. E.; Street, R. A.

    2003-01-01

    Photoelectric X-ray polarimeters based on pixel micropattern gas detectors (MPGDs) offer order-of-magnitude improvement in sensitivity over more traditional techniques based on X-ray scattering. This new technique places some of the most interesting astronomical observations within reach of even a small, dedicated mission. The most sensitive instrument would be a photoelectric polarimeter at the focus of 2 a very large mirror, such as the planned XEUS. Our efforts are focused on a smaller pathfinder mission, which would achieve its greatest sensitivity with large-area, low-background, collimated polarimeters. We have recently demonstrated a MPGD polarimeter using amorphous silicon thin-film transistor (TFT) readout suitable for the focal plane of an X-ray telescope. All the technologies used in the demonstration polarimeter are scalable to the areas required for a high-sensitivity collimated polarimeter. Leywords: X-ray polarimetry, particle tracking, proportional counter, GEM, pixel readout

  11. Plasma Membrane Factor XIIIA Transglutaminase Activity Regulates Osteoblast Matrix Secretion and Deposition by Affecting Microtubule Dynamics

    PubMed Central

    Al-Jallad, Hadil F.; Myneni, Vamsee D.; Piercy-Kotb, Sarah A.; Chabot, Nicolas; Mulani, Amina; Keillor, Jeffrey W.; Kaartinen, Mari T.

    2011-01-01

    Transglutaminase activity, arising potentially from transglutaminase 2 (TG2) and Factor XIIIA (FXIIIA), has been linked to osteoblast differentiation where it is required for type I collagen and fibronectin matrix deposition. In this study we have used an irreversible TG-inhibitor to ‘block –and-track’ enzyme(s) targeted during osteoblast differentiation. We show that the irreversible TG-inhibitor is highly potent in inhibiting osteoblast differentiation and mineralization and reduces secretion of both fibronectin and type I collagen and their release from the cell surface. Tracking of the dansyl probe by Western blotting and immunofluorescence microscopy demonstrated that the inhibitor targets plasma membrane-associated FXIIIA. TG2 appears not to contribute to crosslinking activity on the osteoblast surface. Inhibition of FXIIIA with NC9 resulted in defective secretory vesicle delivery to the plasma membrane which was attributable to a disorganized microtubule network and decreased microtubule association with the plasma membrane. NC9 inhibition of FXIIIA resulted in destabilization of microtubules as assessed by cellular Glu-tubulin levels. Furthermore, NC9 blocked modification of Glu-tubulin into 150 kDa high-molecular weight Glu-tubulin form which was specifically localized to the plasma membrane. FXIIIA enzyme and its crosslinking activity were colocalized with plasma membrane-associated tubulin, and thus, it appears that FXIIIA crosslinking activity is directed towards stabilizing the interaction of microtubules with the plasma membrane. Our work provides the first mechanistic cues as to how transglutaminase activity could affect protein secretion and matrix deposition in osteoblasts and suggests a novel function for plasma membrane FXIIIA in microtubule dynamics. PMID:21283799

  12. Method to evaluate the proliferation of activated lymphocytes in a three-dimensional collagen matrix.

    PubMed

    Davidova, Natalya V; Gorlina, Natalia K; Sharova, Svetlana V; Cheredeev, Anatoly N; Kozlov, Ivan G

    2002-12-01

    It is well known that the enhancement of the cell-matrix interactions represents one of the early steps in the process of lymphocyte activation. However, the information regarding the role of these interactions in the late stages of lymphocyte activation (in particular, the proliferation) is still controversial. This is basically due to the absence of adequate experimental models. In the present work we carried out a step-by-step modification of a well-studied model of mitogen-stimulated lymphocyte activation, adjusting it to the conditions of a three-dimensional collagen matrix (3D-CM). All the changes added to the standard procedure in the process of this modification were rigorously controlled using various experimental models. The final version of the method includes the following steps: (i) 24-h lymphocyte (lymphocyte fraction from mouse spleen) preincubation with mitogens (Con A or LPS) with a subsequent cell wash (parameters being controlled: irreversible lymphocyte activation, independence of the proliferation from cell-cell interactions); (ii) transfer of the activated lymphocytes to (3)H-thymidine containing 3D-CM and incubation for 48 h (controlled parameters: distribution of the radioactive label within the 3D-CM and its biological accessibility to lymphocytes); (iii) degradation of the 3D-CM with bacterial collagenase and cell transfer onto glass fiber filters (controlled parameters: cell viability after cultivation in the 3D-CM and treatment with the collagenase). With this method we found that the proliferation of the Con A- and LPS-stimulated lymphocytes in 3D-CM was dramatically inhibited (by 66.5 +/- 14.9% and by 88.1 +/- 10.2%, respectively). The discovered inhibition of the lymphocyte proliferation was not a consequence of either the ineffectiveness of the mitogens, the disruption of the cell-cell interactions, an insufficient inclusion of the radioactive label into cells, or of a decreased cell viability.

  13. Aryl hydrocarbon receptor activation impairs extracellular matrix remodeling during zebra fish fin regeneration.

    PubMed

    Andreasen, Eric A; Mathew, Lijoy K; Löhr, Christiane V; Hasson, Rachelle; Tanguay, Robert L

    2007-01-01

    Adult zebra fish completely regenerate their caudal (tail) fin following partial amputation. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibits this regenerative process. Proper regulation of transcription, innervation, vascularization, and extracellular matrix (ECM) composition is essential for complete fin regeneration. Previous microarray studies suggest that genes involved in ECM regulation are misexpressed following activation of the aryl hydrocarbon receptor. To investigate whether TCDD blocks regeneration by impairing ECM remodeling, male zebra fish were i.p. injected with 50 ng/g TCDD or vehicle, and caudal fins were amputated. By 3 days postamputation (dpa), the vascular network in the regenerating fin of TCDD-exposed fish was disorganized compared to vehicle-exposed animals. Furthermore, immunohistochemical staining revealed that axonal outgrowth was impacted by TCDD as early as 3 dpa. Histological analysis demonstrated that TCDD exposure leads to an accumulation of collagen at the end of the fin ray just distal to the amputation site by 3 dpa. Mature lepidotrichial-forming cells (fin ray-forming cells) were not observed in the fins of TCDD-treated fish. The capacity to metabolize ECM was also altered by TCDD exposure. Quantitative real-time PCR studies revealed that the aryl hydrocarbon pathway is active and that matrix-remodeling genes are expressed in the regenerate following TCDD exposure.

  14. Gelatinase activity of matrix metalloproteinases in the cerebrospinal fluid of various patient populations.

    PubMed

    Valenzuela, M A; Cartier, L; Collados, L; Kettlun, A M; Araya, F; Concha, C; Flores, L; Wolf, M E; Mosnaim, A D

    1999-01-01

    We have studied the enzymatic gelatinolytic activity of matrix metalloproteinases (MMPs) present in cerebrospinal fluid (CSF) of samples obtained from 67 individuals, twenty-one nonneurological patients (considered controls) and 46 subjects with various neurological disorders e.g., vascular lesions, demyelination, inflammatory, degenerative and prion diseases. Biochemical characterization of MMPs, a family of neutral proteolytic enzymes involved in extracellular matrix modeling, included determination of substrate specificity and Ca+2 dependency, as well as the effects of protease inactivators, carboxylic and His (histidine) residue modifiers, and antibiotics. Whereas all CSF samples expressed MMP-2 (gelatinase A) activity, it corresponded in most cases (normal and pathological samples) to its latent form (proenzyme; pMMP-2). In general, inflammatory neurological diseases (especially meningitis and neurocisticercosis) were associated with the presence of a second enzyme, MMP-9 (or gelatinase B). Whereas MMP-9 was found in the CSF of every tropical spastic paraparesis patient studied, its presence in samples from individuals with vascular lesions was uncommon. Patients blood-brain barrier damage was ascertained by determining total CSF protein content using both, the conventional polyacrylamide gel electrophoresis procedure under denaturing conditions and capillary zone electrophoresis.

  15. Wound fluids from human pressure ulcers contain elevated matrix metalloproteinase levels and activity compared to surgical wound fluids.

    PubMed

    Yager, D R; Zhang, L Y; Liang, H X; Diegelmann, R F; Cohen, I K

    1996-11-01

    Fluid from acute surgical wounds and from nonhealing pressure ulcers was examined for the presence of several matrix metalloproteinases. Gelatin zymography demonstrated the presence of two major gelatinases with apparent molecular masses of 72 kDa and 92 kDa and two minor gelatinases with apparent mobilities of 68 kDa and 125 kDa. Antigen-specific sera identified the 72-kDa protein as matrix melloproteinase-2. The same sera also reacted with the 68-kDa protein, which is consistent with it being an activated form of matrix metalloproteinase-2. Antigen-specific sera identified the 92-kDa and 125-kDa proteins as matrix metalloproteinase-9. Levels of matrix metalloproteinase-2 and matrix metalloproteinase-9 were elevated more than 10-fold and 25-fold, respectively, in fluids from pressure ulcers compared with fluids from healing wounds. Examination of total potential and actual collagenolytic activity revealed that fluid from pressure ulcers contained significantly greater levels of both total and active collagenase compared with that of acute surgical wounds. In addition, an enzyme-linked immunosorbent assay demonstrated that fluids from pressure ulcers contained significantly more collagenase complexed with the inhibitor, tissue inhibitor of metalloproteinases. Together, these observations suggest that an imbalance exists between levels of matrix metalloproteinases and their inhibitors in the fluids of pressure ulcers and that this is primarily the result of elevated levels of the matrix metalloproteinases. The presence of excessive levels of activated forms of matrix-degrading enzymes at the wound surface of pressure ulcers may impede the healing of these wounds and may be relevant to the development of new rationales for treatment.

  16. Using Video-Enhanced Activity Schedules and Matrix Training to Teach Sociodramatic Play to a Child with Autism

    ERIC Educational Resources Information Center

    Dauphin, Melissa; Kinney, Elisabeth M.; Stromer, Robert; Koegel, R. L.

    2004-01-01

    We evaluated an intervention package for teaching generative sociodramatic play activities to a young boy with an autism spectrum disorder. In Phase 1, the boy learned computer activity schedules that featured embedded video models of what to say and do. A 3 x 3 instructional matrix defined 9 activities to be performed involving combinations of 3…

  17. The matrix-binding domain of microfibril-associated glycoprotein-1 targets active connective tissue growth factor to a fibroblast-produced extracellular matrix.

    PubMed

    Weinbaum, Justin S; Tranquillo, Robert T; Mecham, Robert P

    2010-11-10

    It is advantageous to use biomaterials in tissue engineering that stimulate extracellular matrix (ECM) production by the cellular component. Connective tissue growth factor (CTGF) stimulates type I collagen (COL1A1) transcription, but is functionally limited as a free molecule. Using a matrix-binding domain (MBD) from microfibril-associated glycoprotein-1, the fusion protein MBD-CTGF was targeted to the ECM and tested for COL1A1 transcriptional activation. MBD-CTGF produced by the ECM-synthesizing fibroblasts, or provided exogenously, localized to the elastic fiber ECM. MBD-CTGF, but not CTGF alone, led to a two-fold enhancement of COL1A1 expression. This study introduces a targeting technology that can be used to elevate collagen transcription in engineered tissues and thereby improve tissue mechanics.

  18. [Regulation of biochar on matrix enzyme activities and microorganisms around cucumber roots under continuous cropping].

    PubMed

    Zou, Chun-jiao; Zhang, Yong-yong; Zhang, Yi-ming; Guo, Xiao-ou; Li, Ming-jing; Li, Tian-lai

    2015-06-01

    The effects of addition of biochar on the matrix enzymes activity, microorganisms population and microbial community structure were evaluated under cucumber continuous cropping for 6 years (11 rotations). Cucumbers were grown in pots in greenhouse with 5% or 3% of medium (by mass) substituted with biochar. The control consisted of medium alone without biochar. The results showed that the activity of peroxidase was significantly improved to the level of the first rotation crop form 30 to 120 d after planting in both biochar treatments, with the effect of 5% biochar being more significant than that of 3% biochar. However, the neutral phosphatase activity was markedly reduced after biochar treatment. The addition of 5% biochar had significant regulation effect on the activities of invertase and urease from 30 to 90 d after planting, while the addition of 3% biochar had little effect. The populations of bacteria and actinomycetes were increased and the fungi population was reduced in both biochar treatments from 30 to 90 d after planting, and the effect of 5% biochar was more significant than that of 3% biochar. Meanwhile, the addition of biochar significantly increased the diversity of the bacterial community structure. In summary, biochar had obvious regulation effect on soil enzyme activity, microorganism quantity and microbial community in continuous cropping nutrition medium. PMID:26572031

  19. Optical imaging of matrix metalloproteinase-7 activity in vivo using a proteolytic nanobeacon

    PubMed Central

    Scherer, Randy L.; VanSaun, Michael N.; McIntyre, Oliver; Matrisian, Lynn M.

    2009-01-01

    Matrix metalloproteinases (MMPs) are extracellular proteolytic enzymes involved in tumor progression. We present the in vivo detection and quantitation of MMP7 activity using a specific near-infrared polymer-based proteolytic beacon, PB-M7NIR. PB-M7NIR is a pegylated polyamidoamine PAMAM-Generation 4 dendrimer core covalently coupled to a Cy5.5 labeled peptide representing a selective substrate that monitors MMP7 activity (S, sensor), and AF750 as an internal reference to monitor relative substrate concentration (R, reference). In vivo imaging of tumors expressing MMP7 had a median S/R ratio 2.2-fold higher than a bilateral control tumor. Ex-vivo imaging of intestines of multiple intestinal neoplasia (APCMin) mice injected systemically with PB-M7NIR revealed a 6-fold increase in S/R in the adenomas of APCMin mice compared to control intestinal tissue or adenomas from MMP7-null Min mice. PB-M7NIR detected tumor sizes as small as 0.01cm2, and S/R was independent of tumor size. Histological sectioning of xenograft tumors localized the proteolytic signal to the extracellular matrix; MMP7-overexpressing tumors displayed an approximately 300-fold enhancement in S/R compared to non-expressing tumor cells. In APCMin adenomas, the proteolytic signal co-localized with the endogenously-expressed MMP7 protein with S/R ratios approximately 6-fold greater than that of normal intestinal epithelium. PB-M7NIR provides a useful reagent for the in vivo and ex-vivo quantitation and localization of MMP-selective proteolytic activity. PMID:19123982

  20. Optical imaging of matrix metalloproteinase-7 activity in vivo using a proteolytic nanobeacon.

    PubMed

    Scherer, Randy L; VanSaun, Michael N; McIntyre, J Oliver; Matrisian, Lynn M

    2008-01-01

    Matrix metalloproteinases (MMPs) are extracellular proteolytic enzymes involved in tumor progression. We present the in vivo detection and quantitation of MMP7 activity using a specific near-infrared polymer-based proteolytic beacon, PB-M7NIR. PB-M7NIR is a pegylated polyamidoamine PAMAM-Generation 4 dendrimer core covalently coupled to a Cy5.5-labeled peptide representing a selective substrate that monitors MMP7 activity (sensor) and AF750 as an internal reference to monitor relative substrate concentration (reference). In vivo imaging of tumors expressing MMP7 had a median sensor to reference ratio 2.2-fold higher than a that of a bilateral control tumor. Ex vivo imaging of intestines of multiple intestinal neoplasia (APC Min) mice injected systemically with PB-M7NIR revealed a sixfold increase in the sensor to reference ratio in the adenomas of APC Min mice compared with control intestinal tissue or adenomas from MMP7-null Min mice. PB-M7NIR detected tumor sizes as small as 0.01 cm2, and the sensor to reference ratio was independent of tumor size. Histologic sectioning of xenograft tumors localized the proteolytic signal to the extracellular matrix; MMP7-overexpressing tumors displayed an approximately 300-fold enhancement in the sensor to reference ratio compared with nonexpressing tumor cells. In APC Min adenomas, the proteolytic signal colocalized with the endogenously expressed MMP7 protein, with sensor to reference ratios approximately sixfold greater than that of normal intestinal epithelium. PB-M7NIR provides a useful reagent for the in vivo and ex vivo quantitation and localization of MMP-selective proteolytic activity.

  1. Monolithic Active Pixel Matrix with Binary Counters ASIC with nested wells

    NASA Astrophysics Data System (ADS)

    Fahim, F.; Deptuch, G.; Holm, S.; Shenai, A.; Lipton, R.

    2013-04-01

    Monolithic Active Matrix with Binary Counters (MAMBO) V ASIC has been designed for detecting and measuring low energy X-rays. A nested well structure with a buried n-well (BNW) and a deeper buried p-well (BPW) is used to electrically isolate the detector from the electronics. BNW acts as an AC ground to electrical signals and behaves as a shield. BPW allows for a homogenous electric field in the entire detector volume. The ASIC consists of a matrix of 50 × 52 pixels, each of 105x105μm2. Each pixel contains analog functionality accomplished by a charge preamplifier, CR-RC2 shaper and a baseline restorer. It also contains a window comparator with Upper and Lower thresholds which can be individually trimmed by 4 bit DACs to remove systematic offsets. The hits are registered by a 12 bit counter which is reconfigured as a shift register to serially output the data from the entire ASIC.

  2. Physical activity of children: a global matrix of grades comparing 15 countries.

    PubMed

    Tremblay, Mark S; Gray, Casey E; Akinroye, Kingsley; Harrington, Dierdre M; Katzmarzyk, Peter T; Lambert, Estelle V; Liukkonen, Jarmo; Maddison, Ralph; Ocansey, Reginald T; Onywera, Vincent O; Prista, Antonio; Reilly, John J; Rodríguez Martínez, María Pilar; Sarmiento Duenas, Olga L; Standage, Martyn; Tomkinson, Grant

    2014-05-01

    The Active Healthy Kids Canada (AHKC) Report Card on Physical Activity for Children and Youth has been effective in powering the movement to get kids moving by influencing priorities, policies, and practice in Canada. The AHKC Report Card process was replicated in 14 additional countries from 5 continents using 9 common indicators (Overall Physical Activity, Organized Sport Participation, Active Play, Active Transportation, Sedentary Behavior, Family and Peers, School, Community and Built Environment, and Government Strategies and Investments), a harmonized process and a standardized grading framework. The 15 Report Cards were presented at the Global Summit on the Physical Activity of Children in Toronto on May 20, 2014. The consolidated findings are summarized here in the form of a global matrix of grades. There is a large spread in grades across countries for most indicators. Countries that lead in certain indicators lag in others. Overall, the grades for indicators of physical activity (PA) around the world are low/poor. Many countries have insufficient information to assign a grade, particularly for the Active Play and Family and Peers indicators. Grades for Sedentary Behaviors are, in general, better in low income countries. The Community and Built Environment indicator received high grades in high income countries and notably lower grades in low income countries. There was a pattern of higher PA and lower sedentary behavior in countries reporting poorer infrastructure, and lower PA and higher sedentary behavior in countries reporting better infrastructure, which presents an interesting paradox. Many surveillance and research gaps and weaknesses were apparent. International cooperation and cross-fertilization is encouraged to tackle existing challenges, understand underlying mechanisms, derive innovative solutions, and overcome the expanding childhood inactivity crisis. PMID:25426906

  3. Toward Active-Matrix Lab-On-A-Chip: Programmable Electrofluidic control Enaled by Arrayed Oxide Thin Film Transistors

    SciTech Connect

    Noh, Joo Hyon; Noh, Jiyong; Kreit, Eric; Heikenfeld, Jason; Rack, Philip D

    2012-01-01

    Agile micro- and nano-fluidic control is critical to numerous life science and chemical science synthesis as well as kinetic and thermodynamic studies. To this end, we have demonstrated the use of thin film transistor arrays as an active matrix addressing method to control an electrofluidic array. Because the active matrix method minimizes the number of control lines necessary (m + n lines for the m x n element array), the active matrix addressing method integrated with an electrofluidic platform can be a significant breakthrough for complex electrofluidic arrays (increased size or resolution) with enhanced function, agility and programmability. An amorphous indium gallium zinc oxide (a-IGZO) semiconductor active layer is used because of its high mobility of 1-15 cm{sup 2} V{sup -1} s{sup -1}, low-temperature processing and transparency for potential spectroscopy and imaging. Several electrofluidic functionalities are demonstrated using a simple 2 x 5 electrode array connected to a 2 x 5 IGZO thin film transistor array with the semiconductor channel width of 50 {mu}m and mobility of 6.3 cm{sup 2} V{sup -1} s{sup -1}. Additionally, using the TFT device characteristics, active matrix addressing schemes are discussed as the geometry of the electrode array can be tailored to act as a storage capacitor element. Finally, requisite material and device parameters are discussed in context with a VGA scale active matrix addressed electrofluidic platform.

  4. Density-matrix renormalization group algorithm with multi-level active space.

    PubMed

    Ma, Yingjin; Wen, Jing; Ma, Haibo

    2015-07-21

    The density-matrix renormalization group (DMRG) method, which can deal with a large active space composed of tens of orbitals, is nowadays widely used as an efficient addition to traditional complete active space (CAS)-based approaches. In this paper, we present the DMRG algorithm with a multi-level (ML) control of the active space based on chemical intuition-based hierarchical orbital ordering, which is called as ML-DMRG with its self-consistent field (SCF) variant ML-DMRG-SCF. Ground and excited state calculations of H2O, N2, indole, and Cr2 with comparisons to DMRG references using fixed number of kept states (M) illustrate that ML-type DMRG calculations can obtain noticeable efficiency gains. It is also shown that the orbital re-ordering based on hierarchical multiple active subspaces may be beneficial for reducing computational time for not only ML-DMRG calculations but also DMRG ones with fixed M values. PMID:26203012

  5. [Regulation of cell activity by the extracellular matrix: the concept of matrikines].

    PubMed

    Maquart, F X; Siméon, A; Pasco, S; Monboisse, J C

    1999-01-01

    The activity of connective tissue cells is modulated by a number of factors present in their environment. In addition to the soluble factors such as hormones, cytokines or growth factors, cells also receive signals from the surrounding extracellular matrix (ECM) macromolecules. Moreover, they may degrade the ECM proteins and liberate peptides which may by themselves constitute new signals for the surrounding cells. Therefore, an actual regulation loop exists in connective tissue, constituted by peptides generated by ECM degradation and connective tissue cells. The term of "matrikine" has been proposed to designate such ECM-derived peptides able to regulate cell activity. In this review, we summarize some data obtained in our laboratory with two different matrikines: the tripeptide glycyl-histidyl-lysine (GHK) and the heptapeptide cysteinyl-asparaginyl-tyrosyl-tyrosyl-seryl-asparaginyl-serine (CNYYSNS). GHK is a potent activator of ECM synthesis and remodeling, whereas CNYYSNS is able to inhibit polymorphonuclear leukocytes activation and decrease the invasive capacities of cancer cells. PMID:10689625

  6. Matrix metalloproteinase-2 of human carotid atherosclerotic plaques promotes platelet activation. Correlation with ischaemic events.

    PubMed

    Lenti, Massimo; Falcinelli, Emanuela; Pompili, Marcella; de Rango, Paola; Conti, Valentina; Guglielmini, Giuseppe; Momi, Stefania; Corazzi, Teresa; Giordano, Giuseppe; Gresele, Paolo

    2014-06-01

    Purified active matrix metalloproteinase-2 (MMP-2) is able to promote platelet aggregation. We aimed to assess the role of MMP-2 expressed in atherosclerotic plaques in the platelet-activating potential of human carotid plaques and its correlation with ischaemic events. Carotid plaques from 81 patients undergoing endarterectomy were tested for pro-MMP-2 and TIMP-2 content by zymography and ELISA. Plaque extracts were incubated with gel-filtered platelets from healthy volunteers for 2 minutes before the addition of a subthreshold concentration of thrombin receptor activating peptide-6 (TRAP-6) and aggregation was assessed. Moreover, platelet deposition on plaque extracts immobilised on plastic coverslips under high shear-rate flow conditions was measured. Forty-three plaque extracts (53%) potentiated platelet aggregation (+233 ± 26.8%), an effect prevented by three different specific MMP-2 inhibitors (inhibitor II, TIMP-2, moAb anti-MMP-2). The pro-MMP-2/TIMP-2 ratio of plaques potentiating platelet aggregation was significantly higher than that of plaques not potentiating it (3.67 ± 1.21 vs 1.01 ± 0.43, p<0.05). Moreover, the platelet aggregation-potentiating effect, the active-MMP-2 content and the active MMP-2/pro-MMP-2 ratio of plaque extracts were significantly higher in plaques from patients who developed a subsequent major cardiovascular event. In conclusion, atherosclerotic plaques exert a prothrombotic effect by potentiating platelet activation due to their content of MMP-2; an elevated MMP-2 activity in plaques is associated with a higher rate of subsequent ischaemic cerebrovascular events. PMID:24499865

  7. The matrix effect of blueberry, oat meal and milk on polyphenols, antioxidant activity and potential bioavailability.

    PubMed

    Cebeci, Fatma; Şahin-Yeşilçubuk, Neşe

    2014-02-01

    In recent years, ready-to eat breakfast cereals prepared with fruit ingredients have gained particular attention due to their polyphenolic contents and health promoting effects. In this study, the matrix effect of blueberry, oat meal, whole milk or skimmed milk on polyphenols, antioxidative potential as well as their potential bioavailability were investigated. The phenolic properties of whole milk, skimmed milk, blueberry and oat meal were investigated and the changes in combinations of the ingredients were determined. Milk addition decreased the total phenolic, flavonoid and anthocyanin content of samples statistically and had negative effect on antioxidant activity showing differences among different methods. According to HPLC results, it was not possible to detect catechin in mixtures due to milk addition. In vitro digestion method was used to determine potential bioavailability of phenolic compounds. According to in vitro digestion procedure results, whole or skimmed milk did not affect the total phenolic content of the proportion passing to the blood from intestine.

  8. Low Temperature Polycrystalline Silicon Thin Film Transistor Pixel Circuits for Active Matrix Organic Light Emitting Diodes

    NASA Astrophysics Data System (ADS)

    Fan, Ching-Lin; Lin, Yu-Sheng; Liu, Yan-Wei

    A new pixel design and driving method for active matrix organic light emitting diode (AMOLED) displays that use low-temperature polycrystalline silicon thin-film transistors (LTPS-TFTs) with a voltage programming method are proposed and verified using the SPICE simulator. We had employed an appropriate TFT model in SPICE simulation to demonstrate the performance of the pixel circuit. The OLED anode voltage variation error rates are below 0.35% under driving TFT threshold voltage deviation (Δ Vth =± 0.33V). The OLED current non-uniformity caused by the OLED threshold voltage degradation (Δ VTO =+0.33V) is significantly reduced (below 6%). The simulation results show that the pixel design can improve the display image non-uniformity by compensating for the threshold voltage deviation in the driving TFT and the OLED threshold voltage degradation at the same time.

  9. Voltage Drop Compensation Method for Active Matrix Organic Light Emitting Diode Displays

    NASA Astrophysics Data System (ADS)

    Choi, Sang-moo; Ryu, Do-hyung; Kim, Keum-nam; Choi, Jae-beom; Kim, Byung-hee; Berkeley, Brian

    2011-03-01

    In this paper, the conventional voltage drop compensation methods are reviewed and the novel design and driving scheme, the advanced power de-coupled (aPDC) driving method, is proposed to effectively compensate the voltage IR drop of active matrix light emitting diode (AMOLED) displays. The advanced PDC driving scheme can be applied to general AMOLED pixel circuits that have been developed with only minor modification or without requiring modification in pixel circuit. A 14-in. AMOLED panel with the aPDC driving scheme was fabricated. Long range uniformity (LRU) of the 14-in. AMOLED panel was improved from 43% without the aPDC driving scheme, to over 87% at the same brightness by using the scheme and the layout complexity of the panel with new design scheme is less than that of the panel with the conventional design scheme.

  10. Novel Digital Driving Method Using Dual Scan for Active Matrix Organic Light-Emitting Diode Displays

    NASA Astrophysics Data System (ADS)

    Jung, Myoung Hoon; Choi, Inho; Chung, Hoon-Ju; Kim, Ohyun

    2008-11-01

    A new digital driving method has been developed for low-temperature polycrystalline silicon, transistor-driven, active-matrix organic light-emitting diode (AM-OLED) displays by time-ratio gray-scale expression. This driving method effectively increases the emission ratio and the number of subfields by inserting another subfield set into nondisplay periods in the conventional digital driving method. By employing the proposed modified gravity center coding, this method can be used to effectively compensate for dynamic false contour noise. The operation and performance were verified by current measurement and image simulation. The simulation results using eight test images show that the proposed approach improves the average peak signal-to-noise ratio by 2.61 dB, and the emission ratio by 20.5%, compared with the conventional digital driving method.

  11. Driving technology for improving motion quality of active-matrix organic light-emitting diode display

    NASA Astrophysics Data System (ADS)

    Kim, Jongbin; Kim, Minkoo; Kim, Jong-Man; Kim, Seung-Ryeol; Lee, Seung-Woo

    2014-09-01

    This paper reports transient response characteristics of active-matrix organic light emitting diode (AMOLED) displays for mobile applications. This work reports that the rising responses look like saw-tooth waveform and are not always faster than those of liquid crystal displays. Thus, a driving technology is proposed to improve the rising transient responses of AMOLED based on the overdrive (OD) technology. We modified the OD technology by combining it with a dithering method because the conventional OD method cannot successfully enhance all the rising responses. Our method can improve all the transitions of AMOLED without modifying the conventional gamma architecture of drivers. A new artifact is found when OD is applied to certain transitions. We propose an optimum OD selection method to mitigate the artifact. The implementation results show the proposed technology can successfully improve motion quality of scrolling texts as well as moving pictures in AMOLED displays.

  12. Low-Voltage, Low-Power, Organic Light-Emitting Transistors for Active Matrix Displays

    NASA Astrophysics Data System (ADS)

    McCarthy, M. A.; Liu, B.; Donoghue, E. P.; Kravchenko, I.; Kim, D. Y.; So, F.; Rinzler, A. G.

    2011-04-01

    Intrinsic nonuniformity in the polycrystalline-silicon backplane transistors of active matrix organic light-emitting diode displays severely limits display size. Organic semiconductors might provide an alternative, but their mobility remains too low to be useful in the conventional thin-film transistor design. Here we demonstrate an organic channel light-emitting transistor operating at low voltage, with low power dissipation, and high aperture ratio, in the three primary colors. The high level of performance is enabled by a single-wall carbon nanotube network source electrode that permits integration of the drive transistor and the light emitter into an efficient single stacked device. The performance demonstrated is comparable to that of polycrystalline-silicon backplane transistor-driven display pixels.

  13. ZnO:H indium-free transparent conductive electrodes for active-matrix display applications

    NASA Astrophysics Data System (ADS)

    Chen, Shuming; Wang, Sisi

    2014-12-01

    Transparent conductive electrodes based on hydrogen (H)-doped zinc oxide (ZnO) have been proposed for active-matrix (AM) display applications. When fabricated with optimal H plasma power and optimal plasma treatment time, the resulting ZnO:H films exhibit low sheet resistance of 200 Ω/◻ and high average transmission of 85% at a film thickness of 150 nm. The demonstrated transparent conductive ZnO:H films can potentially replace indium-tin-oxide and serve as pixel electrodes for organic light-emitting diodes as well as source/drain electrodes for ZnO-based thin-film transistors. Use of the proposed ZnO:H electrodes means that two photomask stages can be removed from the fabrication process flow for ZnO-based AM backplanes.

  14. ZnO:H indium-free transparent conductive electrodes for active-matrix display applications

    SciTech Connect

    Chen, Shuming Wang, Sisi

    2014-12-01

    Transparent conductive electrodes based on hydrogen (H)-doped zinc oxide (ZnO) have been proposed for active-matrix (AM) display applications. When fabricated with optimal H plasma power and optimal plasma treatment time, the resulting ZnO:H films exhibit low sheet resistance of 200 Ω/◻ and high average transmission of 85% at a film thickness of 150 nm. The demonstrated transparent conductive ZnO:H films can potentially replace indium-tin-oxide and serve as pixel electrodes for organic light-emitting diodes as well as source/drain electrodes for ZnO-based thin-film transistors. Use of the proposed ZnO:H electrodes means that two photomask stages can be removed from the fabrication process flow for ZnO-based AM backplanes.

  15. Density-matrix renormalization-group study of current and activity fluctuations near nonequilibrium phase transitions.

    PubMed

    Gorissen, Mieke; Hooyberghs, Jef; Vanderzande, Carlo

    2009-02-01

    Cumulants of a fluctuating current can be obtained from a free-energy-like generating function, which for Markov processes equals the largest eigenvalue of a generalized generator. We determine this eigenvalue with the density-matrix renormalization group for stochastic systems. We calculate the variance of the current in the different phases, and at the phase transitions, of the totally asymmetric exclusion process. Our results can be described in the terms of a scaling ansatz that involves the dynamical exponent z . We also calculate the generating function of the dynamical activity (total number of configuration changes) near the absorbing-state transition of the contact process. Its scaling properties can be expressed in terms of known critical exponents. PMID:19391693

  16. High performance organic transistor active-matrix driver developed on paper substrate

    NASA Astrophysics Data System (ADS)

    Peng, Boyu; Ren, Xiaochen; Wang, Zongrong; Wang, Xinyu; Roberts, Robert C.; Chan, Paddy K. L.

    2014-09-01

    The fabrication of electronic circuits on unconventional substrates largely broadens their application areas. For example, green electronics achieved through utilization of biodegradable or recyclable substrates, can mitigate the solid waste problems that arise at the end of their lifespan. Here, we combine screen-printing, high precision laser drilling and thermal evaporation, to fabricate organic field effect transistor (OFET) active-matrix (AM) arrays onto standard printer paper. The devices show a mobility and on/off ratio as high as 0.56 cm2V-1s-1 and 109 respectively. Small electrode overlap gives rise to a cut-off frequency of 39 kHz, which supports that our AM array is suitable for novel practical applications. We demonstrate an 8 × 8 AM light emitting diode (LED) driver with programmable scanning and information display functions. The AM array structure has excellent potential for scaling up.

  17. Three-dimensional display utilizing a diffractive optical element and an active matrix liquid crystal display

    NASA Astrophysics Data System (ADS)

    Nordin, Gregory P.; Jones, Michael W.; Kulick, Jeffrey H.; Lindquist, Robert G.; Kowel, Stephen T.

    1996-12-01

    We describe the design, construction, and performance of the first real-time autostereoscopic 3D display based on the partial pixel 3D display architecture. The primary optical components of the 3D display are an active-matrix liquid crystal display and a diffractive optical element (DOE). The display operates at video frame rates and is driven with a conventional VGA signal. 3D animations with horizontal motion parallax are readily viewable as sets of stereo images. Formation of the virtual viewing slits by diffraction from the partial pixel apertures is experimentally verified. The measured contrast and perceived brightness of the display are excellent, but there are minor flaws in image quality due to secondary images. The source of these images and how they may be eliminated is discussed. The effects of manufacturing-related systematic errors in the DOE are also analyzed.

  18. Matrix metalloproteinases 2 and 9 and MMP9/NGAL complex activity in women with PCOS.

    PubMed

    Ranjbaran, Javad; Farimani, Marzieh; Tavilani, Heidar; Ghorbani, Marzieh; Karimi, Jamshid; Poormonsefi, Faranak; Khodadadi, Iraj

    2016-04-01

    It is believed that matrix metalloproteinases (MMPs) play important roles in follicular development and pathogenesis of polycystic ovary syndrome (PCOS). However, conflicting results are available about the alteration of MMP2 and MMP9 concentrations or activities in PCOS. In fact, there is no study entirely investigating both concentration and activity of these MMPs and serum levels of their tissue inhibitors TIMP2 and TIMP1, as well as lipocalin-bound form of MMP9 (MMP9/NGAL). Therefore, the thoroughness of previous studies is questionable. This study was conducted to determine circulatory concentration of MMP2, MMP9, MMP9/NGAL complex, TIMP1 and TIMP2 as well as gelatinase activities of MMP2, MMP9 and MMP9/NGAL complex in women with PCOS and controls. Mean age and BMI as well as serum levels of total cholesterol, triacylglycerol, HDL-C, LDL-C, fasting blood sugar (FBS), insulin, estradiol and sex hormone-binding globulin did not differ between groups, whereas a marked decrease in FSH and significant increases in LH, LH/FSH ratio, testosterone and free androgen index were observed. Women with PCOS and controls showed closed concentrations of MMP2, MMP9, MMP9/NGAL, TIMP1 and TIMP2. Gelatinase activity of MMP9 was found significantly higher in PCOS than in controls (64.53±15.32 vs 44.61±18.95 respectively) while patients and healthy subjects showed similar activities of MMP2 and MMP9/NGAL complex. Additionally, PCOS patients showed a higher MMP9/TIMP1 ratio compared with control women. Direct correlations were also observed between circulatory MMP9 level and the concentration and activity of MMP9/NGAL complex. In conclusion, based on the results of present study, we believe that MMP9 may be involved in the pathogenesis of PCOS.

  19. Back-Side Readout Silicon Photomultiplier

    PubMed Central

    Choong, Woon-Seng; Holland, Stephen E.

    2012-01-01

    We present a novel structure for the back-side readout silicon photomultipler (SiPM). Current SiPMs are front-illuminated structures with front-side readout, which have relatively small geometric fill factor leading to degradation in their photon detection efficiency (PDE). Back-side readout devices will provide an advantageous solution to achieve high PDE. We designed and investigated a novel structure that would allow back-side readout while creating a region of high electric field optimized for avalanche breakdown. In addition, this structure has relatively high fill factor and also allow direct coupling of individual micro-cell of the SiPM to application-specific integrated circuits. We will discuss the performance that can be attained with this structure through device simulation and the process flow that can be used to fabricate this structure through process simulation. PMID:23564969

  20. Multimodal imaging reveals temporal and spatial microglia and matrix metalloproteinase activity after experimental stroke

    PubMed Central

    Zinnhardt, Bastian; Viel, Thomas; Wachsmuth, Lydia; Vrachimis, Alexis; Wagner, Stefan; Breyholz, Hans-Jörg; Faust, Andreas; Hermann, Sven; Kopka, Klaus; Faber, Cornelius; Dollé, Frédéric; Pappata, Sabina; Planas, Anna M; Tavitian, Bertrand; Schäfers, Michael; Sorokin, Lydia M; Kuhlmann, Michael T; Jacobs, Andreas H

    2015-01-01

    Stroke is the most common cause of death and disability from neurologic disease in humans. Activation of microglia and matrix metalloproteinases (MMPs) is involved in positively and negatively affecting stroke outcome. Novel, noninvasive, multimodal imaging methods visualizing microglial and MMP alterations were employed. The spatio-temporal dynamics of these parameters were studied in relation to blood flow changes. Micro positron emission tomography (μPET) using [18F]BR-351 showed MMP activity within the first days after transient middle cerebral artery occlusion (tMCAo), followed by increased [18F]DPA-714 uptake as a marker for microglia activation with a maximum at 14 days after tMCAo. The inflammatory response was spatially located in the infarct core and in adjacent (penumbral) tissue. For the first time, multimodal imaging based on PET, single photon emission computed tomography, and magnetic resonance imaging revealed insight into the spatio-temporal distribution of critical parameters of poststroke inflammation. This allows further evaluation of novel treatment paradigms targeting the postischemic inflammation. PMID:26126867

  1. A Matrix Metalloproteinase-1/Protease Activated Receptor-1 signaling axis promotes melanoma invasion and metastasis

    PubMed Central

    Blackburn, Jessica S.; Liu, Ingrid; Coon, Charles I.; Brinckerhoff, Constance E.

    2009-01-01

    Hallmarks of malignant melanoma are its propensity to metastasize and its resistance to treatment, giving patients with advanced disease a poor prognosis. The transition of melanoma from non-invasive radial growth phase (RGP) to invasive and metastatically competent vertical growth phase (VGP) is a major step in tumor progression, yet the mechanisms governing this transformation are unknown. Matrix Metalloproteinase-1 (MMP-1) is highly expressed by VGP melanomas, and is thought to contribute to melanoma progression by degrading type I collagen within the skin to facilitate melanoma invasion. Protease activated receptor-1 (PAR-1) is activated by MMP-1, and is also expressed by VGP melanomas. However, the effects MMP-1 signaling through PAR-1 have not been examined in melanoma. Here, we demonstrate that an MMP-1/PAR-1 signaling axis exists in VGP melanoma, and is necessary for melanoma invasion. Introduction of MMP-1 into RGP melanoma cells induced gene expression associated with tumor progression and promoted invasion in vitro, and enhanced tumor growth and conferred metastatic capability in vivo. This study demonstrates that both the type I collagenase and PAR-1 activating functions of MMP-1 are required for melanoma progression, and suggests that MMP-1 may be a major contributor to the transformation of melanoma from non-invasive to malignant disease. PMID:19734937

  2. Proliferative effects of apical, but not basal, matrix metalloproteinase-7 activity in polarized MDCK cells

    SciTech Connect

    Harrell, Permila C.; McCawley, Lisa J.; Fingleton, Barbara; McIntyre, J. Oliver; Matrisian, Lynn M. . E-mail: lynn.matrisian@vanderbilt.edu

    2005-02-15

    Matrix metalloproteinase-7 (MMP-7) is primarily expressed in glandular epithelium. Therefore, its mechanism of action may be influenced by its regulated vectorial release to either the apical and/or basolateral compartments, where it would act on its various substrates. To gain a better understanding of where MMP-7 is released in polarized epithelium, we have analyzed its pattern of secretion in polarized MDCK cells expressing stably transfected human MMP-7 (MDCK-MMP-7), and HCA-7 and Caco2 human colon cancer cell lines. In all cell lines, latent MMP-7 was secreted to both cellular compartments, but was 1.5- to 3-fold more abundant in the basolateral compartment as compared to the apical. However, studies in the MDCK system demonstrated that MMP-7 activity was 2-fold greater in the apical compartment of MDCK-MMP-7{sup HIGH}-polarized monolayers, which suggests the apical co-release of an MMP-7 activator. In functional assays, MMP-7 over-expression increased cell saturation density as a result of increased cell proliferation with no effect on apoptosis. Apical MMP-7 activity was shown to be responsible for the proliferative effect, which occurred, as demonstrated by media transfer experiments, through cleavage of an apical substrate and not through the generation of a soluble factor. Taken together, our findings demonstrate the importance of MMP-7 secretion in relation to its mechanism of action when expressed in a polarized epithelium.

  3. Pyrophosphate Stimulates Differentiation, Matrix Gene Expression and Alkaline Phosphatase Activity in Osteoblasts

    PubMed Central

    Pujari-Palmer, Michael; Pujari-Palmer, Shiuli; Lu, Xi; Lind, Thomas; Melhus, Håkan; Engstrand, Thomas; Karlsson-Ott, Marjam; Engqvist, Hakan

    2016-01-01

    Pyrophosphate is a potent mitogen, capable of stimulating proliferation in multiple cell types, and a critical participant in bone mineralization. Pyrophosphate can also affect the resorption rate and bioactivity of orthopedic ceramics. The present study investigated whether calcium pyrophosphate affected proliferation, differentiation and gene expression in early (MC3T3 pre-osteoblast) and late stage (SAOS-2 osteosarcoma) osteoblasts. Pyrophosphate stimulated peak alkaline phosphatase activity by 50% and 150% at 100μM and 0.1μM in MC3T3, and by 40% in SAOS-2. The expression of differentiation markers collagen 1 (COL1), alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OCN) were increased by an average of 1.5, 2, 2 and 3 fold, by high concentrations of sodium pyrophosphate (100μM) after 7 days of exposure in MC3T3. COX-2 and ANK expression did not differ significantly from controls in either treatment group. Though both high and low concentrations of pyrophosphate stimulate ALP activity, only high concentrations (100μM) stimulated osteogenic gene expression. Pyrophosphate did not affect proliferation in either cell type. The results of this study confirm that chronic exposure to pyrophosphate exerts a physiological effect upon osteoblast differentiation and ALP activity, specifically by stimulating osteoblast differentiation markers and extracellular matrix gene expression. PMID:27701417

  4. Computational characterization of ketone-ketal transformations at the active site of matrix metalloproteinases.

    PubMed

    Khrenova, Maria G; Nemukhin, Alexander V; Savitsky, Alexander P

    2014-04-24

    We modeled the first steps of hydrolysis reactions of a natural oligopeptide substrate of matrix metalloproteinase MMP-2 as well as of a substrate analogue. In the latter, the scissile amide group is substituted by a ketomethylene group which can be transformed to the ketal group upon binding of this compound to the enzyme active site. According to our quantum mechanical-molecular mechanical (QM/MM) calculations, the reaction of the ketone-ketal transformation proceeds with a low energy barrier (3.4 kcal/mol) and a high equilibrium constant (10(4)). The reaction product with the ketal group formed directly at the active site of the enzyme works as an inhibitor that chelates the zinc ion. On the other hand, the oligopeptide mimetic retains molecular groups responsible for binding of this compound to the enzyme active site. This example illustrates a strategy to design MMP inhibitors in situ by using data on binding specificity of substrates to a particular type of MMP and details of the reaction mechanism. PMID:24684684

  5. Activity of lung neutrophils and matrix metalloproteinases in cyclophosphamide-treated mice with experimental sepsis

    PubMed Central

    Hirsh, Mark; Carmel, Julie; Kaplan, Viktoria; Livne, Erella; Krausz, Michael M

    2004-01-01

    Sepsis in patients receiving chemotherapy may result in acute respiratory distress syndrome, despite decreased number of blood neutrophils [polymorphonuclear neutrophils (PMNs)]. In the present study, we investigated the correlation of cyclophosphamide (CY)-induced neutropenia with the destructive potential of lung PMN in respect to formation of septic acute lung injury (ALI). Mice were treated with 250 mg/kg of CY or saline (control) and subjected to cecal ligation and puncture (CLP) or sham operation. ALI was verified by histological examination. Lung PMNs and matrix metalloproteinases (MMPs) were assessed by flow cytometry and gelatin zymography. CLP in CY-treated mice induced a typical lung injury. Despite profound neutropenia, CY treatment did not attenuate CLP-induced ALI. This might relate to only a partial suppression of PMN: CY has significantly reduced PMN influx into the lungs (P = 0.008) and suppressed their oxidative metabolism, but had no suppressive effect on degranulation (P = 0.227) and even induced MMP-9 activity (P = 0.0003). In CY-untreated animals, peak of CLP-induced ALI coincided with massive PMN influx (P = 0.013), their maximal degranulation (P = 0.014) and activation of lung MMP-9 (P = 0.002). These findings may indicate an important role of the residual lung PMN and activation of MMP-9 in septic lung injury during CY chemotherapy. PMID:15255968

  6. Dentin phosphophoryn in the matrix activates AKT and mTOR signaling pathway to promote preodontoblast survival and differentiation

    PubMed Central

    Eapen, Asha; George, Anne

    2015-01-01

    Dentin phosphophoryn (DPP) is an extracellular matrix protein synthesized by odontoblasts. It is highly acidic and the phosphorylated protein possesses a strong affinity for calcium ions. Therefore, DPP in the extracellular matrix can promote hydroxyapatite nucleation and can regulate the size of the growing crystal. Besides its calcium binding property, DPP can initiate signaling functions from the ECM (Extracellular matrix). The signals that promote the cytodifferentiation of preodontoblasts to fully functional odontoblasts are not known. In this study, we demonstrate that preodontoblasts on a DPP matrix, generates mechanical and biochemical signals. This is initiated by the ligation of the integrins with the RGD containing DPP. The downstream biochemical response observed is the activation of the AKT(protein kinase B) and mTOR (mammalian target of rapamycin) signaling pathways leading to the activation of the transcription factor NF-κB (Nuclear factor κB). Terminal differentiation of the preodontoblasts was assessed by identifying phosphate and calcium deposits in the matrix using von Kossa and Alizarin red staining respectively. Identifying the signaling pathways initiated by DPP in the dentin matrix would help in devising strategies for dentin tissue engineering. PMID:26300786

  7. PPAR{gamma} agonist pioglitazone reduces matrix metalloproteinase-9 activity and neuronal damage after focal cerebral ischemia

    SciTech Connect

    Lee, Seong-Ryong; Kim, Hahn-Young; Hong, Jung-Suk; Baek, Won-Ki; Park, Jong-Wook

    2009-02-27

    Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPAR{gamma}) agonist, has shown protective effects against ischemic insult in various tissues. Pioglitazone is also reported to reduce matrix metalloproteinase (MMP) activity. MMPs can remodel extracellular matrix components in many pathological conditions. The current study was designed to investigate whether the neuroprotection of pioglitazone is related to its MMP inhibition in focal cerebral ischemia. Mice were subjected to 90 min focal ischemia and reperfusion. In gel zymography, pioglitazone reduced the upregulation of active form of MMP-9 after ischemia. In in situ zymograms, pioglitazone also reduced the gelatinase activity induced by ischemia. After co-incubation with pioglitazone, in situ gelatinase activity was directly reduced. Pioglitazone reduced the infarct volume significantly compared with controls. These results demonstrate that pioglitazone may reduce MMP-9 activity and neuronal damage following focal ischemia. The reduction of MMP-9 activity may have a possible therapeutic effect for the management of brain injury after focal ischemia.

  8. The role of valvular endothelial cell paracrine signaling and matrix elasticity on valvular interstitial cell activation.

    PubMed

    Gould, Sarah T; Matherly, Emily E; Smith, Jennifer N; Heistad, Donald D; Anseth, Kristi S

    2014-04-01

    The effects of valvular endothelial cell (VlvEC) paracrine signaling on VIC phenotype and nodule formation were tested using a co-culture platform with physiologically relevant matrix elasticities and diffusion distance. 100 μm thin poly(ethylene glycol) (PEG) hydrogels of 3-27 kPa Young's moduli were fabricated in transwell inserts. VICs were cultured on the gels, as VIC phenotype is known to change significantly within this range, while VlvECs lined the underside of the membrane. Co-culture with VlvECs significantly reduced VIC activation to the myofibroblast phenotype on all gels with the largest percent decrease on the 3 kPa gels (~70%), while stiffer gels resulted in approximately 20-30% decrease. Additionally, VlvECs significantly reduced αSMA protein expression (~2 fold lower) on both 3 and 27 kPa gels, as well as the number (~2 fold lower) of nodules formed on the 27 kPa gels. Effects of VlvECs were prevented when nitric oxide (NO) release was inhibited with l-NAME, suggesting that VlvEC produced NO inhibits VIC activation. Withdrawal of l-NAME after 3, 5, and 7 days with restoration of VlvEC NO production for 2 additional days led to a partial reversal of VIC activation (~25% decrease). A potential mechanism by which VlvEC produced NO reduced VIC activation was studied by inhibiting initial and mid-stage cGMP pathway molecules. Inhibition of soluble guanylyl cyclase (sGC) with ODQ or protein kinase G (PKG) with RBrcGMP or stimulation of Rho kinase (ROCK) with LPA, abolished VlvEC effects on VIC activation. This work contributes substantially to the understanding of the valve endothelium's role in preventing VIC functions associated with aortic valve stenosis initiation and progression.

  9. Distribution and relative activity of matrix metalloproteinase-2 in human coronal dentin

    PubMed Central

    Boushell, Lee W; Kaku, Masaru; Mochida, Yoshiyuki; Yamauchi, Mitsuo

    2011-01-01

    The presence of matrix metalloproteinase-2 (MMP-2) in dentin has been reported, but its distribution and activity level in mature human coronal dentin are not well understood. The purpose of this study was to determine the MMP-2 distribution and relative activity in demineralized dentin. Crowns of twenty eight human molars were sectioned into inner (ID), middle (MD), and outer dentin (OD) regions and demineralized. MMP-2 was extracted with 0.33 mol·L−1 EDTA/2 mol·L−1 guanidine-HCl, pH 7.4, and MMP-2 concentration was estimated with enzyme-linked immunoabsorbant assay (ELISA). Further characterization was accomplished by Western blotting analysis and gelatin zymography. The mean concentrations of MMP-2 per mg dentin protein in the dentin regions were significantly different (P=0.043): 0.9 ng (ID), 0.4 ng (MD), and 2.2 ng (OD), respectively. The pattern of MMP-2 concentration was OD>ID>MD. Western blotting analysis detected ∼66 and ∼72 kDa immunopositive proteins corresponding to pro- and mature MMP-2, respectively, in the ID and MD, and a ∼66 kDa protein in the OD. Gelatinolytic activity consistent with MMP-2 was detected in all regions. Interestingly, the pattern of levels of Western blot immunodetection and gelatinolytic activity was MD>ID>OD. The concentration of MMP-2 in human coronal dentin was highest in the region of dentin that contains the dentinoenamel junction and least in the middle region of dentin. However, levels of Western blot immunodetection and gelatinolytic activity did not correlate with the estimated regional concentrations of MMP-2, potentially indicating region specific protein interactions. PMID:22010577

  10. Osteoblast-released Matrix Vesicles, Regulation of Activity and Composition by Sulfated and Non-sulfated Glycosaminoglycans.

    PubMed

    Schmidt, Johannes R; Kliemt, Stefanie; Preissler, Carolin; Moeller, Stephanie; von Bergen, Martin; Hempel, Ute; Kalkhof, Stefan

    2016-02-01

    Our aging population has to deal with the increasing threat of age-related diseases that impair bone healing. One promising therapeutic approach involves the coating of implants with modified glycosaminoglycans (GAGs) that mimic the native bone environment and actively facilitate skeletogenesis. In previous studies, we reported that coatings containing GAGs, such as hyaluronic acid (HA) and its synthetically sulfated derivative (sHA1) as well as the naturally low-sulfated GAG chondroitin sulfate (CS1), reduce the activity of bone-resorbing osteoclasts, but they also induce functions of the bone-forming cells, the osteoblasts. However, it remained open whether GAGs influence the osteoblasts alone or whether they also directly affect the formation, composition, activity, and distribution of osteoblast-released matrix vesicles (MV), which are supposed to be the active machinery for bone formation. Here, we studied the molecular effects of sHA1, HA, and CS1 on MV activity and on the distribution of marker proteins. Furthermore, we used comparative proteomic methods to study the relative protein compositions of isolated MVs and MV-releasing osteoblasts. The MV proteome is much more strongly regulated by GAGs than the cellular proteome. GAGs, especially sHA1, were found to severely impact vesicle-extracellular matrix interaction and matrix vesicle activity, leading to stronger extracellular matrix formation and mineralization. This study shows that the regulation of MV activity is one important mode of action of GAGs and provides information on underlying molecular mechanisms.

  11. Osteoblast-released Matrix Vesicles, Regulation of Activity and Composition by Sulfated and Non-sulfated Glycosaminoglycans.

    PubMed

    Schmidt, Johannes R; Kliemt, Stefanie; Preissler, Carolin; Moeller, Stephanie; von Bergen, Martin; Hempel, Ute; Kalkhof, Stefan

    2016-02-01

    Our aging population has to deal with the increasing threat of age-related diseases that impair bone healing. One promising therapeutic approach involves the coating of implants with modified glycosaminoglycans (GAGs) that mimic the native bone environment and actively facilitate skeletogenesis. In previous studies, we reported that coatings containing GAGs, such as hyaluronic acid (HA) and its synthetically sulfated derivative (sHA1) as well as the naturally low-sulfated GAG chondroitin sulfate (CS1), reduce the activity of bone-resorbing osteoclasts, but they also induce functions of the bone-forming cells, the osteoblasts. However, it remained open whether GAGs influence the osteoblasts alone or whether they also directly affect the formation, composition, activity, and distribution of osteoblast-released matrix vesicles (MV), which are supposed to be the active machinery for bone formation. Here, we studied the molecular effects of sHA1, HA, and CS1 on MV activity and on the distribution of marker proteins. Furthermore, we used comparative proteomic methods to study the relative protein compositions of isolated MVs and MV-releasing osteoblasts. The MV proteome is much more strongly regulated by GAGs than the cellular proteome. GAGs, especially sHA1, were found to severely impact vesicle-extracellular matrix interaction and matrix vesicle activity, leading to stronger extracellular matrix formation and mineralization. This study shows that the regulation of MV activity is one important mode of action of GAGs and provides information on underlying molecular mechanisms. PMID:26598647

  12. Matrix rigidity regulates spatiotemporal dynamics of Cdc42 activity and vacuole formation kinetics of endothelial colony forming cells.

    PubMed

    Kim, Seung Joon; Wan, Qiaoqiao; Cho, Eunhye; Han, Bumsoo; Yoder, Mervin C; Voytik-Harbin, Sherry L; Na, Sungsoo

    2014-01-24

    Recent evidence has shown that endothelial colony forming cells (ECFCs) may serve as a cell therapy for improving blood vessel formation in subjects with vascular injury, largely due to their robust vasculogenic potential. The Rho family GTPase Cdc42 is known to play a primary role in this vasculogenesis process, but little is known about how extracellular matrix (ECM) rigidity affects Cdc42 activity during the process. In this study, we addressed two questions: Does matrix rigidity affect Cdc42 activity in ECFC undergoing early vacuole formation? How is the spatiotemporal activation of Cdc42 related to ECFC vacuole formation? A fluorescence resonance energy transfer (FRET)-based Cdc42 biosensor was used to examine the effects of the rigidity of three-dimensional (3D) collagen matrices on spatiotemporal activity of Cdc42 in ECFCs. Collagen matrix stiffness was modulated by varying the collagen concentration and therefore fibril density. The results showed that soft (150 Pa) matrices induced an increased level of Cdc42 activity compared to stiff (1 kPa) matrices. Time-course imaging and colocalization analysis of Cdc42 activity and vacuole formation revealed that Cdc42 activity was colocalized to the periphery of cytoplasmic vacuoles. Moreover, soft matrices generated faster and larger vacuoles than stiff matrices. The matrix-driven vacuole formation was enhanced by a constitutively active Cdc42 mutant, but significantly inhibited by a dominant-negative Cdc42 mutant. Collectively, the results suggest that matrix rigidity is a strong regulator of Cdc42 activity and vacuole formation kinetics, and that enhanced activity of Cdc42 is an important step in early vacuole formation in ECFCs.

  13. High bandwidth deflection readout for atomic force microscopes.

    PubMed

    Steininger, Juergen; Bibl, Matthias; Yoo, Han Woong; Schitter, Georg

    2015-10-01

    This contribution presents the systematic design of a high bandwidth deflection readout mechanism for atomic force microscopes. The widely used optical beam deflection method is revised by adding a focusing lens between the cantilever and the quadrant photodetector (QPD). This allows the utilization of QPDs with a small active area resulting in an increased detection bandwidth due to the reduced junction capacitance. Furthermore the additional lens can compensate a cross talk between a compensating z-movement of the cantilever and the deflection readout. Scaling effects are analyzed to get the optimal spot size for the given geometry of the QPD. The laser power is tuned to maximize the signal to noise ratio without limiting the bandwidth by local saturation effects. The systematic approach results in a measured -3 dB detection bandwidth of 64.5 MHz at a deflection noise density of 62fm/√Hz.

  14. Neutrophil bactericidal activity against Staphylococcus aureus adherent on biological surfaces. Surface-bound extracellular matrix proteins activate intracellular killing by oxygen-dependent and -independent mechanisms.

    PubMed Central

    Hermann, M; Jaconi, M E; Dahlgren, C; Waldvogel, F A; Stendahl, O; Lew, D P

    1990-01-01

    The activation patterns of surface adherent neutrophils are modulated via interaction of extracellular matrix proteins with neutrophil integrins. To evaluate neutrophil bactericidal activity, Staphylococcus aureus adherent to biological surfaces were incubated with neutrophils and serum, and the survival of surface bacteria was determined. When compared to albumin-coated surfaces, the bactericidal activity of neutrophils adherent to purified human extracellular matrix was markedly enhanced (mean survival: 34.2% +/- 9.0% of albumin, P less than 0.0001) despite similar efficient ingestion of extracellular bacteria. Enhancement of killing was observed when surfaces were coated with purified constituents of extracellular matrix, i.e., fibronectin, fibrinogen, laminin, vitronectin, or type IV collagen. In addition to matrix proteins, the tetrapeptide RGDS (the sequence recognized by integrins) crosslinked to surface bound albumin was also active (survival: 74.5% +/- 5.5% of albumin, P less than 0.02), and fibronectin-increased killing was inhibited by soluble RGDS. Chemiluminescence measurements and experiments with CGD neutrophils revealed that both oxygen-dependent and -independent bactericidal mechanisms are involved. In conclusion, matrix proteins enhance intracellular bactericidal activity of adherent neutrophils, presumably by integrin recognition of RGDS-containing ligands. These results indicate a role for extracellular matrix proteins in the enhancement of the host defense against pyogenic infections. Images PMID:2394841

  15. Liquid state machine with dendritically enhanced readout for low-power, neuromorphic VLSI implementations.

    PubMed

    Roy, Subhrajit; Banerjee, Amitava; Basu, Arindam

    2014-10-01

    In this paper, we describe a new neuro-inspired, hardware-friendly readout stage for the liquid state machine (LSM), a popular model for reservoir computing. Compared to the parallel perceptron architecture trained by the p-delta algorithm, which is the state of the art in terms of performance of readout stages, our readout architecture and learning algorithm can attain better performance with significantly less synaptic resources making it attractive for VLSI implementation. Inspired by the nonlinear properties of dendrites in biological neurons, our readout stage incorporates neurons having multiple dendrites with a lumped nonlinearity (two compartment model). The number of synaptic connections on each branch is significantly lower than the total number of connections from the liquid neurons and the learning algorithm tries to find the best 'combination' of input connections on each branch to reduce the error. Hence, the learning involves network rewiring (NRW) of the readout network similar to structural plasticity observed in its biological counterparts. We show that compared to a single perceptron using analog weights, this architecture for the readout can attain, even by using the same number of binary valued synapses, up to 3.3 times less error for a two-class spike train classification problem and 2.4 times less error for an input rate approximation task. Even with 60 times larger synapses, a group of 60 parallel perceptrons cannot attain the performance of the proposed dendritically enhanced readout. An additional advantage of this method for hardware implementations is that the 'choice' of connectivity can be easily implemented exploiting address event representation (AER) protocols commonly used in current neuromorphic systems where the connection matrix is stored in memory. Also, due to the use of binary synapses, our proposed method is more robust against statistical variations.

  16. Performance studies of a Micromegas detector with a pad readout geometry

    NASA Astrophysics Data System (ADS)

    Düdder, A.; Lin, T.-H.; Neuhaus, F.; Schott, M.; Valderanis, C.

    2016-07-01

    The results of several performance studies of two prototype Micromegas pad detectors with two different coupling implementations between the resistive and the readout layer are presented. Both prototype detectors have an active area of 10 × 10cm2 and comprise 500 pads with a size of 5 × 4mm2. The first detector has a capacitive coupling between the resistive and the readout layer, as it is well known from Micromegas detectors with a strip readout. The second detector implements a resistive coupling between each readout pad and the resistive layer on top of it with a resistivity of 5 MΩ. In particular, the size of reconstructed charge clusters in both detector types is discussed and compared here for different drift- and amplification voltages.

  17. Study of the spatial resolution for binary readout detectors

    NASA Astrophysics Data System (ADS)

    Yonamine, R.; Maerschalk, T.; Lentdecker, G. De

    2016-07-01

    Often the binary readout is proposed for high granularity detectors to reduce the generated data volume to be readout at the price of a somewhat reduced spatial resolution compared to an analogue readout. We have been studying single hit resolutions obtained with a binary readout using simulations as well as analytical approaches. In this note we show that the detector geometry could be optimized to offer an equivalent spatial resolution than with an analogue readout.

  18. Biomimetic Mineralization of the Alginate/Gelatin/Calcium Oxalate Matrix for Immobilization of Pectinase: Influence of Matrix on the Pectinolytic Activity.

    PubMed

    Bustamante-Vargas, Cindy Elena; de Oliveira, Débora; Valduga, Eunice; Venquiaruto, Luciana Dornelles; Paroul, Natalia; Backes, Geciane Toniazzo; Dallago, Rogério Marcos

    2016-07-01

    Pectinases catalyze the degradation of pectic substances and are used in several processes, mainly in food and textile industries. In this study, a biomimetic matrix of alginate/gelatin/calcium oxalate (AGOCa) was synthesized for the in situ immobilization via encapsulation of crude pectinase from Aspergillus niger ATCC 9642, obtaining an immobilization efficiency of about 61.7 %. To determine the performance of AGOCa matrix, this was compared to control matrices of alginate/calcium oxalate (AOxal) and alginate/water (ACa). By the evaluation of pH and temperature effects on the enzyme activity, it was observed an increase on pectinolytic activity for both three tested matrices with an increase on pH and temperature. The kinetic parameters for pectinase immobilized in the three matrices were determined using citric pectin as substrate. Values of K m of 0.003, 0.0013, and 0.0022 g mL(-1) and V max of 3.85, 4.32, and 3.17 μmol min(-1) g(-1) for AGOCa, AOxal, and ACa matrices were obtained, respectively. After 33 days of storage, the pectinase immobilized in the three different matrices kept its initial activity, but that immobilized in AGOCa presented high stability to the storage with a relative activity of about 160 %. The enzyme immobilized in AGOCa, AOxal, and ACa could be used in 10, 8, and 7 cycles, respectively, keeping 40 % of its initial activity.

  19. Differential expression of matrix metalloproteinases in activated c-ras-Ha-transfected immortalized human keratinocytes.

    PubMed Central

    Meade-Tollin, L. C.; Boukamp, P.; Fusenig, N. E.; Bowen, C. P.; Tsang, T. C.; Bowden, G. T.

    1998-01-01

    Elevated expression of matrix metalloproteinases (MMPs), a family of secreted proteinases that degrade matrix components of basement membranes and connective tissues, is strongly correlated with malignant expression in various human epithelial cancers and epithelial cancer cell lines. We have tested whether elevated levels of MMP expression are also associated with malignant progression in human cutaneous squamous cell carcinoma. Constitutive levels of expression of steady-state mRNA and of secreted protein encoded by three MMP genes (matrilysin, gelatinases A and B) were compared in a unique in vitro model of human skin carcinogenesis. This model is composed of the parental immortalized non-tumorigenic human keratinocyte line (HaCaT), and three activated c-Harvey-ras-oncogene transfected variants (A-4, I-7 and II-4). Although clone A-4 is non-tumorigenic, clones I-7 and II-4 exhibit benign and malignant tumorigenic phenotypes, respectively, after subcutaneous injection into athymic nude mice. Northern blot, Western blot, and zymogram analyses revealed three MMP-specific patterns of expression. Constitutive matrilysin mRNA expression was markedly increased in the I-7 cells compared with HaCaT, A-4 or II-4 cells. Secreted promatrilysin was distinctly increased in the tumorigenic I-7 and II-4 cells compared with the non-tumorigenic HaCaT and A-4 cells. Gelatinase A mRNA and secreted gelatinase A protein levels were increased in each transfectant compared with HaCaT. Both active and inactive forms of gelatinase A were detected. Gelatinase B transcripts were not detected, but an EDTA-inhibitable gelatinase activity comigrating with gelatinase B was moderately enhanced in both tumorigenic variants compared with the non-tumorigenic cells. Because promatrilysin and 92-kDa gelatinase secretion were increased in both benign and malignant tumorigenic cells, and not related to invasiveness in this model, it is concluded that enhanced constitutive expression of these two MMPs

  20. Human retinal pigment epithelial lysis of extracellular matrix: functional urokinase plasminogen activator receptor, collagenase, and elastase.

    PubMed Central

    Elner, Susan G

    2002-01-01

    PURPOSE: To show (1) human retinal pigment epithelial (HRPE) expression of functional urokinase plasminogen activator receptor (uPAR; CD87), (2) HRPE secretion of collagenase and elastase, (3) uPAR-dependent HRPE migration, and (4) uPAR expression in diseased human retinal tissue. METHODS: Immunohistochemistry for uPAR was performed on cultured HRPE cells and in sections of human retina. Double-immunofluorescent staining of live human RPE cells with anti-CR3 antibody (CD11b) was performed to demonstrate the physical proximity of this beta 2 integrin with uPAR and determine whether associations were dependent on RPE confluence and polarity. Extracellular proteolysis by HRPE uPAR was evaluated using fluorescent bodipy-BSA and assessed for specificity by plasminogen activator inhibitor-1 (PAI-1) inhibition. The effect of interleukin-1 beta (IL-1 beta) on uPAR expression was assessed. Collagenase and elastase secretion by unstimulated and IL-1-stimulated HRPE cells was measured by 3H-labelled collagen and elastin cleavage. HRPE-associated collagenase was also assessed by cleavage of fluorescent DQ-collagen and inhibited by phenanthroline. Using an extracellular matrix assay, the roles of uPAR and collagenase in HRPE migration were assessed. RESULTS: Immunoreactive uPAR was detected on cultured HRPE cells and increased by IL-1. On elongated, live HRPE cells, uPAR dissociated from CD11b (CR3) and translocated to anterior poles of migrating cells. Extracellular proteolysis was concentrated at sites of uPAR expression and specifically inhibited by PAI-1. Cultured HRPE cells secreted substantial, functional collagenase and elastase. IL-1 upregulated uPAR, collagenase, and elastase activities. Specific inhibition of uPAR, and to a lesser degree collagenase, reduced HRPE migration in matrix/gel assays. Immunoreactive uPAR was present along the HRPE basolateral membrane in retinal sections and in sections of diseased retinal tissue. CONCLUSIONS: HRPE cells express functional u

  1. Dexamethasone-Mediated Activation of Fibronectin Matrix Assembly Reduces Dispersal of Primary Human Glioblastoma Cells

    PubMed Central

    Shannon, Stephen; Vaca, Connan; Jia, Dongxuan; Entersz, Ildiko; Schaer, Andrew; Carcione, Jonathan; Weaver, Michael; Avidar, Yoav; Pettit, Ryan; Nair, Mohan; Khan, Atif; Foty, Ramsey A.

    2015-01-01

    Despite resection and adjuvant therapy, the 5-year survival for patients with Glioblastoma multiforme (GBM) is less than 10%. This poor outcome is largely attributed to rapid tumor growth and early dispersal of cells, factors that contribute to a high recurrence rate and poor prognosis. An understanding of the cellular and molecular machinery that drive growth and dispersal is essential if we are to impact long-term survival. Our previous studies utilizing a series of immortalized GBM cell lines established a functional causation between activation of fibronectin matrix assembly (FNMA), increased tumor cohesion, and decreased dispersal. Activation of FNMA was accomplished by treatment with Dexamethasone (Dex), a drug routinely used to treat brain tumor related edema. Here, we utilize a broad range of qualitative and quantitative assays and the use of a human GBM tissue microarray and freshly-isolated primary human GBM cells grown both as conventional 2D cultures and as 3D spheroids to explore the role of Dex and FNMA in modulating various parameters that can significantly influence tumor cell dispersal. We show that the expression and processing of fibronectin in a human GBM tissue-microarray is variable, with 90% of tumors displaying some abnormality or lack in capacity to secrete fibronectin or assemble it into a matrix. We also show that low-passage primary GBM cells vary in their capacity for FNMA and that Dex treatment reactivates this process. Activation of FNMA effectively “glues” cells together and prevents cells from detaching from the primary mass. Dex treatment also significantly increases the strength of cell-ECM adhesion and decreases motility. The combination of increased cohesion and decreased motility discourages in vitro and ex vivo dispersal. By increasing cell-cell cohesion, Dex also decreases growth rate of 3D spheroids. These effects could all be reversed by an inhibitor of FNMA and by the glucocorticoid receptor antagonist, RU-486. Our

  2. Bilayer Membrane Modulation of Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) Structure and Proteolytic Activity.

    PubMed

    Cerofolini, Linda; Amar, Sabrina; Lauer, Janelle L; Martelli, Tommaso; Fragai, Marco; Luchinat, Claudio; Fields, Gregg B

    2016-01-01

    Cell surface proteolysis is an integral yet poorly understood physiological process. The present study has examined how the pericellular collagenase membrane-type 1 matrix metalloproteinase (MT1-MMP) and membrane-mimicking environments interplay in substrate binding and processing. NMR derived structural models indicate that MT1-MMP transiently associates with bicelles and cells through distinct residues in blades III and IV of its hemopexin-like domain, while binding of collagen-like triple-helices occurs within blades I and II of this domain. Examination of simultaneous membrane interaction and triple-helix binding revealed a possible regulation of proteolysis due to steric effects of the membrane. At bicelle concentrations of 1%, enzymatic activity towards triple-helices was increased 1.5-fold. A single mutation in the putative membrane interaction region of MT1-MMP (Ser466Pro) resulted in lower enzyme activation by bicelles. An initial structural framework has thus been developed to define the role(s) of cell membranes in modulating proteolysis. PMID:27405411

  3. Sustained activation of neutrophils in the course of Kawasaki disease: an association with matrix metalloproteinases.

    PubMed

    Biezeveld, M H; van Mierlo, G; Lutter, R; Kuipers, I M; Dekker, T; Hack, C E; Newburger, J W; Kuijpers, T W

    2005-07-01

    Kawasaki disease (KD) is an acute febrile syndrome of childhood, characterized by vasculitis of the medium-sized arteries. White blood cell counts and the inflammatory parameter C-reactive protein (CRP) are known to be elevated in the acute phase of the disease. In this study we investigated the course of inflammatory cell type-specific parameters in KD over a longer period of time. Plasma levels of human neutrophil elastase (HNE), matrix metalloproteinases-2 and -9 (MMP2, MMP9), and neutrophil gelatinase-associated lipocalin (NGAL), macrophage neopterin and CRP were measured. Plasma samples were collected in the acute, subacute and early convalescent stage, and three months after the onset of disease. Median CRP and neopterin normalized within two weeks. In contrast, six weeks and three months after onset of disease, levels of HNE were still elevated, with median values of 163 ng/ml and 156 ng/ml, respectively (control children median < 50 ng/ml; for all time-points P < 0.0001). Values of NGAL correlated with the levels of HNE (r = 0.39, P = 0.013). These results demonstrate a longer state of neutrophil activation in KD than was previously assumed. The potential relationship between this prolonged neutrophil activation, coronary artery lesion formation and their persistence, as well as the risk of premature atherosclerosis warrants further evaluation.

  4. Influence of neutron activation factors on matrix tablets for site specific delivery to the colon.

    PubMed

    Ahrabi, S F; Heinämäki, J; Sande, S A; Graffner, C

    2000-05-01

    The impact of the neutron activation procedure, i.e. incorporation of samarium oxide (Sm(2)O(3)) and neutron irradiation, on the compression properties (including the crushing strength) and in vitro dissolution of potential colonic delivery systems based on matrix tablets of amidated pectin (Am.P) or two types of hydroxypropyl methylcellulose (HPMC) was investigated. The neutron activation factors did not influence the compression properties of the tablets. Replacement of magnesium stearate with samarium stearate in directly compressed Am.P tablets to achieve both radiolabelling and lubrication resulted in a greater extent of concentration-dependent reduction of the crushing strength. Dissolution tests demonstrated that irradiation increased the release of the model drug ropivacaine from the tablets. The extent of this increase was unexpectedly low considering the previously observed degradation of the polymer expressed as an irradiation-induced viscosity reduction in solutions prepared from the polymers. Delayed-release coating with Eudragit L 100 protected the HPMC tablets against the release-increasing effect of irradiation until the late phases of release. Sm(2)O(3) retarded the release to a varying extent depending on particle characteristics. Incorporation of Sm(2)O(3) in the coating layer did not influence the release. However, one-third of the radioactivity leached from the coating within 60 min in 0.1 M HCl. PMID:10767600

  5. Augmented expression of urokinase plasminogen activator and extracellular matrix proteins associates with multiple myeloma progression.

    PubMed

    Khan, Rehan; Gupta, Nidhi; Kumar, Raman; Sharma, Manoj; Kumar, Lalit; Sharma, Alpana

    2014-06-01

    Multiple myeloma (MM) represents a B cell malignancy, characterized by a monoclonal proliferation of malignant plasma cells. Interactions between tumor cells and extracellular matrix (ECM) are of importance for tumor invasion and metastasis. Protein levels of urokinase plasminogen activator (uPA) and fibulin 1, nidogen and laminin in plasma and serum respectively and mRNA levels of these molecules in peripheral blood mononuclear cells were determined in 80 subjects by using ELISA and quantitative PCR and data was analyzed with severity of disease. Pearson correlation was determined to observe interrelationship between different molecules. A statistical significant increase for ECM proteins (laminin, nidogen and fibulin 1) and uPA at circulatory level as well as at mRNA level was observed compared to healthy controls. The levels of these molecules in serum might be utilized as a marker of active disease. Significant positive correlation of all ECM proteins with uPA was found and data also correlates with severity of disease. Strong association found between ECM proteins and uPA in this study supports that there might be interplay between these molecules which can be targeted. This study on these molecules may help to gain insight into processes of growth, spread, and clinical behavior of MM.

  6. Antimicrobial activities of silver used as a polymerization catalyst for a wound-healing matrix

    PubMed Central

    Babu, Ranjith; Zhang, Jianying; Beckman, Eric J.; Virji, Mohammed; Pasculle, William A.; Wells, Alan

    2007-01-01

    Wound healing is a complex and orchestrated process that re-establishes the barrier and other functions of the skin. While wound healing proceeds apace in healthy individual, bacterial overgrowth and infection disrupts this process with significant morbidity and mortality. As such, any artificial matrix to promote wound healing must also control infecting microbes. We had earlier developed a two-part space-conforming gel backbone based on polyethyleneglycol (PEG) or lactose, which used ionic silver as the catalyst for gelation. As silver is widely used as an in vitro antimicrobial, use of silver as a catalyst for gelation provided the opportunity to assess its function as an anti-microbial agent in the gels. We found that these gels show bacteriostatic and bactericidal activity for a range of Gram-negative and Gram-positive organisms, including aerobic as well as anaerobic bacteria. This activity lasted for days, as silver leached out of the formed gels over a day in the manner of second-order decay. Importantly the gels did not limit either cell growth or viability, though cell migration was affected. Adding collagen I fragments to the gels corrected this effect on cell migration. We also found that the PEG gel did not interfere with hemostasis. These observations provide the basis for use of the gel backbones for incorporation of anesthetic agents and factors that promote wound repair. In conclusion, silver ions can serve dual functions of catalyzing gelation and providing anti-microbial properties to a biocompatible polymer. PMID:16635526

  7. Bilayer Membrane Modulation of Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) Structure and Proteolytic Activity

    PubMed Central

    Cerofolini, Linda; Amar, Sabrina; Lauer, Janelle L.; Martelli, Tommaso; Fragai, Marco; Luchinat, Claudio; Fields, Gregg B.

    2016-01-01

    Cell surface proteolysis is an integral yet poorly understood physiological process. The present study has examined how the pericellular collagenase membrane-type 1 matrix metalloproteinase (MT1-MMP) and membrane-mimicking environments interplay in substrate binding and processing. NMR derived structural models indicate that MT1-MMP transiently associates with bicelles and cells through distinct residues in blades III and IV of its hemopexin-like domain, while binding of collagen-like triple-helices occurs within blades I and II of this domain. Examination of simultaneous membrane interaction and triple-helix binding revealed a possible regulation of proteolysis due to steric effects of the membrane. At bicelle concentrations of 1%, enzymatic activity towards triple-helices was increased 1.5-fold. A single mutation in the putative membrane interaction region of MT1-MMP (Ser466Pro) resulted in lower enzyme activation by bicelles. An initial structural framework has thus been developed to define the role(s) of cell membranes in modulating proteolysis. PMID:27405411

  8. A genetic fiber modification to achieve matrix-metalloprotease-activated infectivity of oncolytic adenovirus.

    PubMed

    José, Anabel; Rovira-Rigau, Maria; Luna, Jeroni; Giménez-Alejandre, Marta; Vaquero, Eva; García de la Torre, Beatriz; Andreu, David; Alemany, Ramon; Fillat, Cristina

    2014-10-28

    Selective tumor targeting of oncolytic adenovirus at the level of cell entry remains a major challenge to improve efficacy and safety. Matrix metalloproteases (MMPs) are overexpressed in a variety of tumors and in particular in pancreatic cancer. In the current work, we have exploited the expression of MMPs together with the penetration capabilities of a TAT-like peptide to engineer tumor selective adenoviruses. We have generated adenoviruses containing CAR-binding ablated fibers further modified with a C-terminus TAT-like peptide linked to a blocking domain by an MMP-cleavable sequence. This linker resulted in a MMP-dependent cell transduction of the reporter MMP-activatable virus AdTATMMP and in efficient transduction of neoplastic cells and cancer-associated fibroblasts. Intravenous and intraductal administration of AdTATMMP into mice showed very low AdTATMMP activity in the normal pancreas, whereas increased transduction was observed in pancreatic tumors of transgenic Ela-myc mice. Intraductal administration of AdTATMMP into mice bearing orthotopic tumors led to a 25-fold increase in tumor targeting compared to the wild type fiber control. A replication competent adenovirus, Ad(RC)MMP, with the MMP-activatable fiber showed oncolytic efficacy and increased antitumor activity compared to Adwt in a pancreatic orthotopic model. Reduced local and distant metastases were observed in Ad(RC)MMP treated-mice. Moreover, no signs of pancreatic toxicity were detected. We conclude that MMP-activatable adenovirus may be beneficial for pancreatic cancer treatment.

  9. Withaferin A inhibits matrix metalloproteinase-9 activity by suppressing the Akt signaling pathway.

    PubMed

    Lee, Dae Hyung; Lim, In-Hye; Sung, Eon-Gi; Kim, Joo-Young; Song, In-Hwan; Park, Yoon Ki; Lee, Tae-Jin

    2013-08-01

    Withaferin A (Wit A), a steroidal lactone isolated from Withania somnifera, exhibits anti-inflammatory, immuno-modulatory and anti-angiogenic properties and antitumor activities. In the present study, we investigated the effects of Wit A on protease-mediated invasiveness of the human metastatic cancer cell lines Caski and SK-Hep1. We found that treatment with Wit A resulted in marked inhibition of the TGF‑β‑induced increase in expression and activity of matrix metalloproteinase (MMP)‑9 in Caski cell line. These effects of Wit A were dose-dependent and showed a correlation with suppression of MMP‑9 mRNA expression levels. Treatment with Wit A resulted in an ~1.6-fold induction of MMP-9 promoter activity, which was also suppressed by treatment with Wit A in Caski cells. We found that treatment with Wit A resulted in inhibition of TGF‑β‑induced phosphorylation of Akt, which was involved in the downregulation of expression of MMP-9 at the protein level. Introduction with constitutively active (CA)‑Akt resulted in a partial increase in the secretion of TGF-β-induced MMP-9 blocked by treatment with Wit A in Caski cells. According to these results, Wit A may inhibit the invasive and migratory abilities of Caski cells through a reduction in MMP-9 expression through suppression of the pAkt signaling pathway. These findings indicate that use of Wit A may be an effective strategy for control of metastasis and invasiveness of tumors.

  10. Acrolein activates matrix metalloproteinases by increasing reactive oxygen species in macrophages

    SciTech Connect

    O'Toole, Timothy E. Zheng Yuting; Hellmann, Jason; Conklin, Daniel J.; Barski, Oleg; Bhatnagar, Aruni

    2009-04-15

    Acrolein is a ubiquitous component of environmental pollutants such as automobile exhaust, cigarette, wood, and coal smoke. It is also a natural constituent of several foods and is generated endogenously during inflammation or oxidation of unsaturated lipids. Because increased inflammation and episodic exposure to acrolein-rich pollutants such as traffic emissions or cigarette smoke have been linked to acute myocardial infarction, we examined the effects of acrolein on matrix metalloproteinases (MMPs), which destabilize atherosclerotic plaques. Our studies show that exposure to acrolein resulted in the secretion of MMP-9 from differentiated THP-1 macrophages. Acrolein-treatment of macrophages also led to an increase in reactive oxygen species (ROS), free intracellular calcium ([Ca{sup 2+}]{sub i}), and xanthine oxidase (XO) activity. ROS production was prevented by allopurinol, but not by rotenone or apocynin and by buffering changes in [Ca{sup 2+}]{sub I} with BAPTA-AM. The increase in MMP production was abolished by pre-treatment with the antioxidants Tiron and N-acetyl cysteine (NAC) or with the xanthine oxidase inhibitors allopurinol or oxypurinol. Finally, MMP activity was significantly stimulated in aortic sections from apoE-null mice containing advanced atherosclerotic lesions after exposure to acrolein ex vivo. These observations suggest that acrolein exposure results in MMP secretion from macrophages via a mechanism that involves an increase in [Ca{sup 2+}]{sub I}, leading to xanthine oxidase activation and an increase in ROS production. ROS-dependent activation of MMPs by acrolein could destabilize atherosclerotic lesions during brief episodes of inflammation or pollutant exposure.

  11. Sync Matrix

    2004-12-31

    Sync Matrix provides a graphic display of the relationships among all of the response activities of each jurisdiction. This is accomplished through software that organizes and displays the activities by jurisdiction, function, and time for easy review and analysis. The software can also integrate the displays of multiple jurisdictions to allow examination of the total response.

  12. Atmospheric-Pressure Cold Plasmas Used to Embed Bioactive Compounds in Matrix Material for Active Packaging of Fruits and Vegetables

    NASA Astrophysics Data System (ADS)

    Fernandez, Sulmer; Pedrow, Patrick; Powers, Joseph; Pitts, Marvin

    2009-10-01

    Active thin film packaging is a technology with the potential to provide consumers with new fruit and vegetable products-if the film can be applied without deactivating bioactive compounds.Atmospheric pressure cold plasma (APCP) processing can be used to activate monomer with concomitant deposition of an organic plasma polymerized matrix material and to immobilize a bioactive compound all at or below room temperature.Aims of this work include: 1) immobilize an antimicrobial in the matrix; 2) determine if the antimicrobial retains its functionality and 3) optimize the reactor design.The plasma zone will be obtained by increasing the voltage on an electrode structure until the electric field in the feed material (argon + monomer) yields electron avalanches. Results will be described using Red Delicious apples.Prospective matrix precursors are vanillin and cinnamic acid.A prospective bioactive compound is benzoic acid.

  13. Airway mucus obstruction triggers macrophage activation and matrix metalloproteinase 12-dependent emphysema.

    PubMed

    Trojanek, Joanna B; Cobos-Correa, Amanda; Diemer, Stefanie; Kormann, Michael; Schubert, Susanne C; Zhou-Suckow, Zhe; Agrawal, Raman; Duerr, Julia; Wagner, Claudius J; Schatterny, Jolanthe; Hirtz, Stephanie; Sommerburg, Olaf; Hartl, Dominik; Schultz, Carsten; Mall, Marcus A

    2014-11-01

    Whereas cigarette smoking remains the main risk factor for emphysema, recent studies in β-epithelial Na(+) channel-transgenic (βENaC-Tg) mice demonstrated that airway surface dehydration, a key pathophysiological mechanism in cystic fibrosis (CF), caused emphysema in the absence of cigarette smoke exposure. However, the underlying mechanisms remain unknown. The aim of this study was to elucidate mechanisms of emphysema formation triggered by airway surface dehydration. We therefore used expression profiling, genetic and pharmacological inhibition, Foerster resonance energy transfer (FRET)-based activity assays, and genetic association studies to identify and validate emphysema candidate genes in βENaC-Tg mice and patients with CF. We identified matrix metalloproteinase 12 (Mmp12) as a highly up-regulated gene in lungs from βENaC-Tg mice, and demonstrate that elevated Mmp12 expression was associated with progressive emphysema formation, which was reduced by genetic deletion and pharmacological inhibition of MMP12 in vivo. By using FRET reporters, we show that MMP12 activity was elevated on the surface of airway macrophages in bronchoalveolar lavage from βENaC-Tg mice and patients with CF. Furthermore, we demonstrate that a functional polymorphism in MMP12 (rs2276109) was associated with severity of lung disease in CF. Our results suggest that MMP12 released by macrophages activated on dehydrated airway surfaces may play an important role in emphysema formation in the absence of cigarette smoke exposure, and may serve as a therapeutic target in CF and potentially other chronic lung diseases associated with airway mucus dehydration and obstruction. PMID:24828142

  14. Piezoelectric properties of the new generation active matrix hybrid (micro-nano) composites

    NASA Astrophysics Data System (ADS)

    Parali, Levent; Şabikoğlu, İsrafil; Kurbanov, Mirza A.

    2014-11-01

    A hybrid piezoelectric composite structure is obtained by addition of nano-sized BaTiO3, SiO2 to the micro-sized PZT and polymers composition. Although the PZT material itself has excellent piezoelectric properties, PZT-based composite variety is limited. Piezoelectric properties of PZT materials can be varied with an acceptor or a donor added to the material. In addition, varieties of PZT-based sensors can be increased with doping polymers which have physical-mechanical, electrophysical, thermophysical and photoelectrical properties. The active matrix hybrid structure occurs when bringing together the unique piezoelectric properties of micro-sized PZT with electron trapping properties of nano-sized insulators (BaTiO3 or SiO2), and their piezoelectric, mechanic and electromechanic properties significantly change. In this study, the relationship between the piezoelectric constant and the coupling factor values of microstructure (PZT-PVDF) and the hybrid structure (PZT-PVDF-BaTiO3) composite are compared. The d33 value and the coupling factor of the hybrid structure have shown an average of 54 and 62% increase according to microstructure composite, respectively. In addition, the d33 value and the coupling factor of the hybrid structure (PZT-HDPE-SiO2) have exhibited about 68 and 52% increase according to microstructure composite (PZT-HDPE), respectively.

  15. Organic thin-film transistor arrays for active-matrix organic light emitting diode

    NASA Astrophysics Data System (ADS)

    Lee, Sangyun; Moon, Hyunsik; Kim, Do H.; Koo, Bon-Won; Jeong, Eun-Jeong; Lee, Bang-Lin; Kim, Joo-Young; Lee, Eunkyung; Hahn, Kook-Min; Han, Jeong-Seok; Park, Jung-Il; Seon, Jong-Baek; Kim, Jung-Woo; Chun, Young-Tea; Kim, Sangyeol; Kang, Sung K.

    2007-09-01

    We developed an active matrix organic light-emitting diodes (AMOLEDs) on a glass using two organic thin-film transistors (OTFTs) and a capacitor in a pixel. OTFTs switching-arrays with 64 scan lines and 64 (RGB) data lines were designed and fabricated to drive OLED arrays. In this study, OTFT devices have bottom contact structures with an ink-jet printed polymer semiconductor and an organic insulator as a gate dielectric. The width and length of the switching OTFT is 500μm and 10μm, respectively and the driving OTFT has 900μm channel width with the same channel length. The characteristics of the OTFTs were examined using test cells around display area. On/off ratio, mobility, on-current of switching OTFT and on-current of driving OTFT were 10 6, 0.1 cm2/V-sec, order of 8μA and over 70 μA respectively. These properties were enough to drive the AMOLEDs over 60 Hz frame rate. AMOLEDs composed of the OTFT switching arrays and OLEDs made by deposition of small molecule materials were fabricated and driven to make moving images, successfully.

  16. Stretchable active-matrix organic light-emitting diode display using printable elastic conductors

    NASA Astrophysics Data System (ADS)

    Sekitani, Tsuyoshi; Nakajima, Hiroyoshi; Maeda, Hiroki; Fukushima, Takanori; Aida, Takuzo; Hata, Kenji; Someya, Takao

    2009-06-01

    Stretchability will significantly expand the applications scope of electronics, particularly for large-area electronic displays, sensors and actuators. Unlike for conventional devices, stretchable electronics can cover arbitrary surfaces and movable parts. However, a large hurdle is the manufacture of large-area highly stretchable electrical wirings with high conductivity. Here, we describe the manufacture of printable elastic conductors comprising single-walled carbon nanotubes (SWNTs) uniformly dispersed in a fluorinated rubber. Using an ionic liquid and jet-milling, we produce long and fine SWNT bundles that can form well-developed conducting networks in the rubber. Conductivity of more than 100Scm-1 and stretchability of more than 100% are obtained. Making full use of this extraordinary conductivity, we constructed a rubber-like stretchable active-matrix display comprising integrated printed elastic conductors, organic transistors and organic light-emitting diodes. The display could be stretched by 30-50% and spread over a hemisphere without any mechanical or electrical damage.

  17. Active matrix organic light emitting diode (OLED)-XL life test results

    NASA Astrophysics Data System (ADS)

    Fellowes, David A.; Wood, Michael V.; Hastings, Arthur R., Jr.; Ghosh, Amalkumar P.; Prache, Olivier

    2008-04-01

    OLED displays have been known to exhibit high levels of performance with regards to contrast, response time, uniformity, and viewing angle, but a lifetime improvement has been perceived to be essential for broadening the applications of OLED's in the military and in the commercial market. As a result of this need, the US Army and eMagin Corporation established a Cooperative Research and Development Agreement (CRADA) to improve the lifetime of OLED displays. In 2006, eMagin Corporation developed long-life OLED-XL devices for use in their AMOLED microdisplays for head-worn applications, and RDECOM CERDEC NVESD ran life tests on these displays, finding over 200% lifetime improvement for the XL devices over the standard displays. Early results were published at the 2007 SPIE Defense and Security Symposium. Further life testing of XL and standard devices at ambient conditions and at high temperatures will be presented this year along with a recap of previous data. This should result in a better understanding of the applicability of AMOLEDs in military and commercial head mounted systems: where good fits are made, and where further development might be needed. This is a continuation of the paper "Life test results of OLED-XL long-life devices for use in active matrix organic light emitting diode (AMOLED) displays for head mounted applications" presented at SPIE DSS in 2007.

  18. Separated Carbon Nanotube Macroelectronics for Active Matrix Organic Light-Emitting Diode Displays

    NASA Astrophysics Data System (ADS)

    Fu, Yue; Zhang, Jialu; Wang, Chuan; Chen, Pochiang; Zhou, Chongwu

    2012-02-01

    Active matrix organic light-emitting diode (AMOLED) display holds great potential for the next generation visual technologies due to its high light efficiency, flexibility, lightweight, and low-temperature processing. However, suitable thin-film transistors (TFTs) are required to realize the advantages of AMOLED. Pre-separated, semiconducting enriched carbon nanotubes are excellent candidates for this purpose because of their excellent mobility, high percentage of semiconducting nanotubes, and room-temperature processing compatibility. Here we report, for the first time, the demonstration of AMOLED displays driven by separated nanotube thin-film transistors (SN-TFTs) including key technology components such as large-scale high-yield fabrication of devices with superior performance, carbon nanotube film density optimization, bilayer gate dielectric for improved substrate adhesion to the deposited nanotube film, and the demonstration of monolithically integrated AMOLED display elements with 500 pixels driven by 1000 SN-TFTs. Our approach can serve as the critical foundation for future nanotube-based thin-film display electronics.

  19. Trivalent metal ions based on inorganic compounds with in vitro inhibitory activity of matrix metalloproteinase 13.

    PubMed

    Wen, Hanyu; Qin, Yuan; Zhong, Weilong; Li, Cong; Liu, Xiang; Shen, Yehua

    2016-10-01

    Collagenase-3 (MMP-13) inhibitors have attracted considerable attention in recent years and have been developed as a therapeutic target for a variety of diseases, including cancer. Matrix metalloproteinases (MMPs) can be inhibited by a multitude of compounds, including hydroxamic acids. Studies have shown that materials and compounds containing trivalent metal ions, particularly potassium hexacyanoferrate (III) (K3[Fe(CN)6]), exhibit cdMMP-13 inhibitory potential with a half maximal inhibitory concentration (IC50) of 1.3μM. The target protein was obtained by refolding the recombinant histidine-tagged cdMMP-13 using size exclusion chromatography (SEC). The secondary structures of the refolded cdMMP-13 with or without metal ions were further analyzed via circular dichroism and the results indicate that upon binding with metal ions, an altered structure with increased domain stability was obtained. Furthermore, isothermal titration calorimetry (ITC) experiments demonstrated that K3[Fe(CN)6]is able to bind to MMP-13 and endothelial cell tube formation tests provide further evidence for this interaction to exhibit anti-angiogenesis potential. To the best of our knowledge, no previous report of an inorganic compound featuring a MMP-13 inhibitory activity has ever been reported in the literature. Our results demonstrate that K3[Fe(CN)6] is useful as a new effective and specific inhibitor for cdMMP-13 which may be of great potential for future drug screening applications. PMID:27542739

  20. Estimating nonnegative matrix model activations with deep neural networks to increase perceptual speech quality.

    PubMed

    Williamson, Donald S; Wang, Yuxuan; Wang, DeLiang

    2015-09-01

    As a means of speech separation, time-frequency masking applies a gain function to the time-frequency representation of noisy speech. On the other hand, nonnegative matrix factorization (NMF) addresses separation by linearly combining basis vectors from speech and noise models to approximate noisy speech. This paper presents an approach for improving the perceptual quality of speech separated from background noise at low signal-to-noise ratios. An ideal ratio mask is estimated, which separates speech from noise with reasonable sound quality. A deep neural network then approximates clean speech by estimating activation weights from the ratio-masked speech, where the weights linearly combine elements from a NMF speech model. Systematic comparisons using objective metrics, including the perceptual evaluation of speech quality, show that the proposed algorithm achieves higher speech quality than related masking and NMF methods. In addition, a listening test was performed and its results show that the output of the proposed algorithm is preferred over the comparison systems in terms of speech quality. PMID:26428778

  1. Probing matrix and tumor mechanics with in situ calibrated optical trap based active microrheology

    NASA Astrophysics Data System (ADS)

    Staunton, Jack Rory; Vieira, Wilfred; Tanner, Kandice; Tissue Morphodynamics Unit Team

    Aberrant extracellular matrix deposition and vascularization, concomitant with proliferation and phenotypic changes undergone by cancer cells, alter mechanical properties in the tumor microenvironment during cancer progression. Tumor mechanics conversely influence progression, and the identification of physical biomarkers promise improved diagnostic and prognostic power. Optical trap based active microrheology enables measurement of forces up to 0.5 mm within a sample, allowing interrogation of in vitro biomaterials, ex vivo tissue sections, and small organisms in vivo. We fabricated collagen I hydrogels exhibiting distinct structural properties by tuning polymerization temperature Tp, and measured their shear storage and loss moduli at frequencies 1-15k Hz at multiple amplitudes. Lower Tp gels, with larger pore size but thicker, longer fibers, were stiffer than higher Tp gels; decreasing strain increased loss moduli and decreased storage moduli at low frequencies. We subcutanously injected probes with metastatic murine melanoma cells into mice. The excised tumors displayed storage and loss moduli 40 Pa and 10 Pa at 1 Hz, increasing to 500 Pa and 1 kPa at 15 kHz, respectively.

  2. Alternatives to low-temperature poly-Si technology in active matrix displays

    NASA Astrophysics Data System (ADS)

    Flores, James S.

    2001-04-01

    Incorporating low temperature poly-Si (LTPS) technology as an active matrix (AM) in flat panel displays (FPDs) has been a struggle and remains costly. The situation motivates companies to investigate alternative AM technologies. Some projects try to relieve the low temperature constraint by switching the substrate material to a metal foil. Some companies try simply to make the most out of a-Si:H technology. Another strategy is to replace silicons as the TFT channel material. Examples include CdSe and even an organic material like pentacene. When crystalline silicon is considered best, engineers consider how to replace excimer laser annealing (ELA) and its cost. A prominent example is the effort at MIT, which printed devices with a kind of 'semiconductor ink'. The best prospects for inexpensive AM backplanes may be plastic transistors and c-Si block assembly. Current leaders of AM technology, a-Si:H and ELA- LTPS, might still end up offering better overall performance, but their costs will probably be higher.

  3. The New APD Based Readout for the Crystal Barrel Calorimeter

    NASA Astrophysics Data System (ADS)

    Urban, M.; Honisch, Ch; Steinacher, M.; CBELSA/TAPS Collaboration

    2015-02-01

    The CBELSA/TAPS experiment at ELSA measures double polarization observables in meson photoproduction off protons and neutrons. To be able to measure purely neutral reactions off polarized neutrons with high efficiency, the main calorimeter has to be integrated into the first level trigger. This requires to exchange the existing PIN photo diode by a new avalanche photo diode (APD) readout. The newly developed readout electronics will provide an energy resolution compatible to the previous set-up and a fast trigger signal down to 10 MeV energy deposit per crystal. After the successful final tests with a 3x3 CsI crystal matrix in Bonn at ELSA and in Mainz at MAMI all front-end electronics were produced in fall 2013. Automated test routines for the front-end electronics were developed and the characterization measurements of all APDs were successfully accomplished in Bonn. The project is supported by the Deutsche Forschungsgemeinschaft (SFB/TR16) and Schweizerischer Nationalfonds.

  4. High-speed position readout for microchannel plate-based space plasma instruments

    NASA Astrophysics Data System (ADS)

    Kataria, D. O.; Chaudery, Rahil; Rees, Kerrin

    2007-04-01

    Position sensitive micro-channel plate (MPC) detectors are attractive for space plasma instruments but have a number of limitations. Most of the techniques have limited global rate handling and require the MCP to run at high gain with MCP lifetime implications. In addition, available mass and power resources limit the number of channels of readout electronics. A fast position sensing technique was developed that is well suited for MCP-based space plasma applications. The output charge from the MCP falling on an anode pixel is capacitively split into two separate channels of readout electronics. Choosing an appropriate readout pattern, the charge is forced to split unequally, introducing a time walk between the signals from the following leading edge discriminator. Identifying the active channels and the order of their arrival time provides unique identification of the position of the incoming event. The pixels are interleaved so that each readout channel can be connected to several pixels, reducing the total number of readout channels. The timing logic and signal processing is carried out within an FPGA with additional processor/spacecraft interfaces also built in. The system dead time within the FPGA has been simulated and found to be less than 100 ns. The performance of the system can be optimised depending on the resolution, rate handling and lifetime requirements of the instrument. Details of the readout technique and its implementation in a space plasma analyser are presented.

  5. Biosensing of matrix metalloproteinase activity with Cd-free quantum dots

    NASA Astrophysics Data System (ADS)

    Plumley, John Bryan

    Quantum dots (QDs) have become attractive in the biomedical field on account of their superior optical properties and stability, in comparison to traditional fluorophores. QDs also have properties which make them ideal for complex in vivo conditions. However, toxicity has been a chief concern in the eventual implementation of QDs for in vivo applications such as biosensing and tumor imaging. Commercially available QDs contain a notoriously noxious Cd component and therefore continuous research has gone into developing QDs without toxic heavy metals, generally Cd, that would still yield comparable performance in terms of their optical properties. Nonetheless, even in the case of Cd-free QDs, toxicity should be evaluated on a case by case basis, as other properties such as size, coating, stability, and charge can affect toxicity of nanomaterials as well, making it a very complex issue. With the high promise of QDs in the field of biomedical development as a motivation, this work strives to develop the efficient and repeatable synthesis of Cd-free QDs with high stability and luminescence, with proven low toxicity, and the ability to detect active matrix metalloproteinase (MMP) in a biosensing system, designed to identify direct biomarkers for pathological conditions, which in turn would enable early disease diagnosis and better treatment development. In this work, highly luminescent ZnSe:Mn/ZnS QDs have been synthesized, characterized, and modified with peptides with a bioconjugation procedure that utilized thiol-metal affinity. Experiments aiming at MMP detection were conducted using the peptide/QD conjugates. In addition, the ApoTox-Glo(TM) Triplex assay was utilized to evaluate cytotoxicity, and a safe concentration below 0.125 microM was identified for peptide-coated ZnSe:Mn/ZnS QDs in water. Finally, in contribution to developing an in vivo fiberoptic system for sensing MMP activity, the QDs were successfully tethered to silica and MMP detection was demonstrated

  6. Hyper Suprime-Cam: CCD readout electronics

    NASA Astrophysics Data System (ADS)

    Nakaya, Hidehiko; Uchida, Tomohisa; Miyatake, Hironao; Aihara, Hiroaki; Doi, Yoshiyuki; Furusawa, Hisanori; Karoji, Hiroshi; Kamata, Yukiko; Kawanomoto, Satoshi; Komiyama, Yutaka; Miyazaki, Satoshi; Morokuma, Tomoki; Tanaka, Manobu; Tanaka, Yoko

    2008-07-01

    Hyper Suprime-Cam is planned to employ about 120 2k×4k fully-depleted CCDs with 4 signal outputs for each. The data size of an image becomes larger than 2Gbytes. All of the CCDs are designed to be readout parallel within 20 seconds, and the readout noise is expected to be 5e. The frontend electronics will be mounted in a vacuumed cryostat, and connected to the backend electronics mounted on the outside of the cryostat. The frontend electronics includes entire analog circuits for CCD including CCD drivers, preamplifiers and ADC. The backend electronics consists of newly developed gigabit Ethernet modules combined with 2Gbytes memory modules, and several supporting boards. We will present the current status of the CCD readout electronics developments for HSC.

  7. D-Zero muon readout electronics design

    SciTech Connect

    Baldin, B.; Hansen, S.; Los, S.; Matveev, M.; Vaniev, V.

    1996-11-01

    The readout electronics designed for the D{null} Muon Upgrade are described. These electronics serve three detector subsystems and one trigger system. The front-ends and readout hardware are synchronized by means of timing signals broadcast from the D{null} Trigger Framework. The front-end electronics have continuously running digitizers and two levels of buffering resulting in nearly deadtimeless operation. The raw data is corrected and formatted by 16- bit fixed point DSP processors. These processors also perform control of the data buffering. The data transfer from the front-end electronics located on the detector platform is performed by serial links running at 160 Mbit/s. The design and test results of the subsystem readout electronics and system interface are discussed.

  8. Perineuronal nets of extracellular matrix around hippocampal interneurons resist destruction by activated microglia in trimethyltin-treated rats.

    PubMed

    Schüppel, Karin; Brauer, Kurt; Härtig, Wolfgang; Grosche, Jens; Earley, Bernadette; Leonard, Brian E; Brückner, Gert

    2002-12-27

    The destruction of the extracellular matrix by inflammatory processes may induce neuronal dysfunction and accelerate neurodegeneration. We describe that chondroitin sulphate proteoglycan-immunoreactive perineuronal nets and the enwrapped interneurons persisted 2 weeks after trimethyltin intoxication of rats (TMT, 8 mg/kg, i.p.) in all regions of the severely affected hippocampus and dentate gyrus, whereas the diffuse immunoreactivity around the CA2 pyramidal cells was reduced. Fluoro-Jade staining of degenerating neurons and staining of microglia by Griffonia simplicifolia agglutinin showed that net-associated neurons survived in the vicinity of damaged pyramidal cells and that perineuronal nets were not removed by activated microglia. We conclude that the extracellular matrix of perineuronal nets resists destruction after TMT treatment in the inflamed neural tissue. A permanent reconstitution of matrix components may be one of the factors that may support the viability of distinct types of neurons during neurodegenerative diseases.

  9. Determination of fission neutron transmission through waste matrix material using neutron signal correlation from active assay of {sup 239}Pu

    SciTech Connect

    Hollas, C.L.; Arnone, G.; Brunson, G.; Coop, K.

    1996-09-01

    The accuracy of TRU (transuranic) waste assay using the differential die-away technique depends upon significant corrections to compensate for the effects of the matrix material in which the TRU waste is located. The authors have used a new instrument, the Combined Thermal/Epithermal Neutron (CTEN) instrument for the assay of TRU waste, to develop methods to improve the accuracy of these corrections. Neutrons from a pulsed 14-MeV neutron generator are moderated in the walls of the CTEN cavity and induce fission in the TRU material. The prompt neutrons from these fission events are detected in cadmium-wrapped {sup 3}He neutron detectors. They report new methods of data acquisition and analysis to extract correlation in the neutron signals resulting form fission during active interrogation. They use the correlation information in conjunction with the total number of neutrons to determine the fraction of fission neutrons transmitted through the matrix material into the {sup 3}He detectors. This determination allows them to cleanly separate the matrix effects into two processes: matrix modification upon the neutron interrogating flux and matrix modification upon the fraction of fission neutrons transmitted to the neutron detectors. This transmission information is also directly applied in a neutron multiplicity analysis in the passive assay of {sup 240}Pu.

  10. Low-background direct readout array performance

    NASA Technical Reports Server (NTRS)

    Goebel, J. H.; Mckelvey, M. E.; Mccreight, C. R.; Anderson, G. M.

    1986-01-01

    The development and evaluation of an integrated array of antimony-doped silicon detectors is described. The spectral range of extrinsic silicon-integrated arrays useful for low-background IR astronomical applications is extended to about 31 microns with this development. The 58 x 62-element array is accessed by a direct readout multiplexer. The device is evaluated with a flexible microcomputer-based drive and readout electronics system in a low-background test dewar. Acceptance testing indicates single-pixel NEPs in the mid-10 to the -18th W/sq rt Hz range, and good global uniformity statistics.

  11. Demountable readout technologies for optical image intensifiers

    NASA Astrophysics Data System (ADS)

    Lapington, J. S.; Howorth, J. R.; Milnes, J. S.

    2007-04-01

    We describe a generic microchannel plate intensifier design for use with a variety of demountable readout devices manufactured using standard multi-layer PCB techniques. We present results obtained using a 50 Ω multi-element design optimized for high speed operation and a four electrode multi-layer device developed from the wedge and strip anode with enhanced image resolution. The benefits of this intensifier design are discussed and a project to develop a detector system for bio-medical applications using a demountable readout device with integrated multi-channel ASIC-based electronics is announced.

  12. Spectral contents readout of birefringent sensor

    NASA Technical Reports Server (NTRS)

    Redner, Alex S.

    1989-01-01

    The technical objective of this research program was to develop a birefringent sensor, capable of measuring strain/stress up to 2000 F and a readout system based on Spectral Contents analysis. As a result of the research work, a data acquisition system was developed, capable of measuring strain birefringence in a sensor at 2000 F, with multi-point static and dynamic capabilities. The system uses a dedicated spectral analyzer for evaluation of stress-birefringence and a PC-based readout. Several sensor methods were evaluated. Fused silica was found most satisfactory. In the final evaluation, measurements were performed up to 2000 F and the system performance exceeded expectations.

  13. Bounds on probability of state transfer with respect to readout time and edge weight

    NASA Astrophysics Data System (ADS)

    Gordon, Whitney; Kirkland, Steve; Li, Chi-Kwong; Plosker, Sarah; Zhang, Xiaohong

    2016-02-01

    We analyze the sensitivity of a spin chain modeled by an undirected weighted connected graph exhibiting perfect state transfer to small perturbations in readout time and edge weight in order to obtain physically relevant bounds on the probability of state transfer. At the heart of our analysis is the concept of the numerical range of a matrix; our analysis of edge weight errors additionally makes use of the spectral and Frobenius norms.

  14. Fabrication issues for silicon backplane active matrix miniature liquid crystal display

    NASA Astrophysics Data System (ADS)

    Underwood, Ian; Burns, D. C.; Rankine, I. D.; Bennett, D. J.; Gourlay, James D.; O'Hara, Anthony; Vass, David G.

    1995-09-01

    We describe a new technology which is appropriate for the production of lightweight, highly compact displays. It is based upon a thin layer of ferroelectric liquid crystal (FLC) on top of, and directly driven by, an active matrix backplane fabricated on single crystal silicon. While devices can be produced using fairly standard techniques, we have developed custon fabrication and packaging techniques, required for optimization of optical quality and performance. We have successfully developed the technology for spatial light modulators for use in applications such as optical correlators and programmable holograms. The FLC is configured in the binary surface stabilized configuration: the CMOS circuits are digital in nature. The device operates in reflection with each pixel having an aluminium pad which acts as a mirror to reflect light and as an electorde to control the state of the overlying FLC. The technology also shows promise as a display technology so we have demonstrated the devices as displays capable of displaying both grey scale and color. We have built FLC devices upon commercially fabricated wafers but have found it advantageous to carry out custom post processing order to improve performance. The main thrust to date has been the use of ECR oxide deposition followed by chemical mechanical polishing to provide an optically flat substrate for mirror deposition. This allows the deposition of flat mirrors which fill almost all of the pixel area; it also allows optimization of the mirror deposition for high optical quality and good FLC alignment. Work is also well advanced on a technique to fill the vias connecting to the mirror layer and on packaging devices to reduce bowing of the silicon and increase the thickness uniformity of the FLC layer. Recent results are demonstrated on LCDs fabricated above two silicon backplanes containing 176 X 176 pixels and 256 X 256 pixels respectively, the former having dynamic signal storage at each pixel, the latter static

  15. Performance of a direct-detection active matrix flat panel dosimeter (AMFPD) for IMRT measurements

    SciTech Connect

    Chen Yu; Moran, Jean M.; Roberts, Donald A.; El-Mohri, Youcef; Antonuk, Larry E.; Fraass, Benedick A.

    2007-12-15

    The dosimetric performance of a direct-detection active matrix flat panel dosimeter (AMFPD) is reported for intensity modulated radiation therapy (IMRT) measurements. The AMFPD consists of a-Si:H photodiodes and thin-film transistors deposited on a glass substrate with no overlying scintillator screen or metal plate. The device is operated at 0.8 frames per second in a continuous acquisition or fluoroscopic mode. The effect of the applied bias voltage across the photodiodes on the response of the AMFPD was evaluated because this parameter affects dark signal, lag contributions, and pixel sensitivity. In addition, the AMPFD response was evaluated as a function of dose, dose rate, and energy, for static fields at 10 cm depth. In continuous acquisition mode, the AMFPD maintained a linear dose response (r{sup 2}>0.99999) up to at least 1040 cGy. In order to obtain reliable integrated dose results for IMRT fields, the effects of lag on the radiation signal were minimized by operating the system at the highest frame rate and at an appropriate reverse bias voltage. Segmental MLC and dynamic MLC IMRT fields were measured with the AMFPD, and the results were compared to film, using standard methods for reliable film dosimetry. Both AMFPD and film measurements were independently converted to dose in cGy. {gamma} and {chi} values were calculated as indices of agreement. The results from the AMFPD were in excellent agreement with those from film. When 2% of D{sub max} and 2 mm of distance to agreement were used as the criteria, 98% of the region of interest (defined as the region where dose is greater than 5% of D{sub max}) satisfied |{chi}|{<=}1 on average across the cases that were tested.

  16. The capacitive division image readout: a novel imaging device for microchannel plate detectors

    NASA Astrophysics Data System (ADS)

    Lapington, J. S.; Conneely, T. M.; Leach, S. A.; Moore, L.

    2013-09-01

    The Capacitive Division Image Readout (C-DIR) is a simple and novel image readout for photon counting detectors offering major performance advantages. C-DIR is a charge centroiding device comprising three elements; (i) a resistive anode providing event charge localization, event current return path and electrical isolation from detector high voltage, (ii) a dielectric substrate which capacitively couples the event transient signal to the third element, (iii) the readout device; an array of capacitively coupled electrodes which divides the signal among the readout charge measurement nodes. The resistive anode and dielectric substrate constitute the rear interface of the detector and capacitively couple the signal to the external C-DIR readout device. The C-DIR device is a passive, multilayer printed circuit board type device comprising a matrix of isolated electrodes whose geometries define the capacitive network. C-DIR is manufactured using conventional PCB geometries and is straightforward and economical to construct. C-DIR's robustness and simplicity belie its performance advantages. Its capacitive nature avoids partition noise, the Poisson noise associated with collection of discrete charges. The dominant noise limiting position resolution is electronic noise. However C-DIR also presents a low input capacitance to the readout electronics, minimising this noise component thus maximising spatial resolution. Optimisation of the C-DIR pattern-edge geometry can provide ~90% linear dynamic range. We present data showing image resolution and linearity of the C-DIR device in a microchannel plate detector and describe various electronic charge measurement scheme designed to exploit the full performance potential of the C-DIR device.

  17. Proanthocyanidins from the American Cranberry (Vaccinium macrocarpon) inhibit matrix metalloproteinase-2 and matrix metalloproteinase-9 activity in human prostate cancer cells via alterations in multiple cellular signalling pathways.

    PubMed

    Déziel, Bob A; Patel, Kunal; Neto, Catherine; Gottschall-Pass, Katherine; Hurta, Robert A R

    2010-10-15

    Prostate cancer is one of the most common cancers in the Western world, and it is believed that an individual's diet affects his risk of developing cancer. There has been an interest in examining phytochemicals, the secondary metabolites of plants, in order to determine their potential anti-cancer activities in vitro and in vivo. In this study we document the effects of proanthocyanidins (PACs) from the American Cranberry (Vaccinium macrocarpon) on matrix metalloproteinase (MMP) activity in DU145 human prostate cancer cells. Cranberry PACs decreased cellular viability of DU145 cells at a concentration of 25 µg/ml by 30% after 6 h of treatment. Treatment of DU145 cells with PACs resulted in an inhibition of both MMPs 2 and 9 activity. PACs increased the expression of TIMP-2, a known inhibitor of MMP activity, and decreased the expression of EMMPRIN, an inducer of MMP expression. PACs decreased the expression of PI-3 kinase and AKT proteins, and increased the phosphorylation of both p38 and ERK1/2. Cranberry PACs also decreased the translocation of the NF-κB p65 protein to the nucleus. Cranberry PACs increased c-jun and decreased c-fos protein levels. These results suggest that cranberry PACs decreases MMP activity through the induction and/or inhibition of specific temporal MMP regulators, and by affecting either the phosphorylation status and/or expression of MAP kinase, PI-3 kinase, NF-κB and AP-1 pathway proteins. This study further demonstrates that cranberry PACs are a strong candidate for further research as novel anti-cancer agents.

  18. Expression and activation of matrix metalloproteinases in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+.

    PubMed

    Siméon, A; Monier, F; Emonard, H; Gillery, P; Birembaut, P; Hornebeck, W; Maquart, F X

    1999-06-01

    We investigated the expression and activation of matrix metalloproteinases in a model of experimental wounds in rats, and their modulation by glycyl-L-histidyl-L-lysine-Cu(II), a potent activator of wound repair. Wound chambers were inserted under the skin of Sprague-Dawley rats and received serial injections of either 2 mg glycyl-L-histidyl-L-lysine-Cu(II) or the same volume of saline. The wound fluid and the neosynthetized connective tissue deposited in the chambers were collected and analyzed for matrix metalloproteinase expression and/or activity. Interstitial collagenase increased progressively in the wound fluid throughout the experiment. Glycyl-L-histidyl-L-lysine-Cu(II) treatment did not alter its activity. Matrix metalloproteinase-9 (gelatinase B) and matrix metalloproteinase-2 (gelatinase A) were the two main gelatinolytic activities expressed during the healing process. Pro-matrix metalloproteinase (pro-form of matrix metalloproteinase)-9 was strongly expressed during the early stages of wound healing (day 3). In the wound fluid, it decreased rapidly and disappeared after day 18, whereas in the wound tissue, matrix metalloproteinase-9 expression persisted in the glycyl-L-histidyl-L-lysine-Cu(II) injected chamber until day 22. Pro-matrix metalloproteinase-2 was expressed at low levels at the beginning of the healing process, increased progressively until day 7, then decreased until day 18. Activated matrix metalloproteinase-2 was present in wound fluid and wound tissue. It increased until day 12, then decreased progressively. Glycyl-L-histidyl-L-lysine-Cu(II) injections increased pro-matrix metalloproteinase-2 and activated matrix metalloproteinase-2 during the later stages of healing (days 18 and/or 22). These results demonstrate that various types of matrix metalloproteinases are selectively expressed or activated at the various periods of wound healing. Glycyl-L-histidyl-L-lysine-Cu(II) is able to modulate their expression and might significantly alter

  19. Flax Fiber Hydrophobic Extract Inhibits Human Skin Cells Inflammation and Causes Remodeling of Extracellular Matrix and Wound Closure Activation

    PubMed Central

    Styrczewska, Monika; Kostyn, Anna; Kulma, Anna; Majkowska-Skrobek, Grazyna; Augustyniak, Daria; Prescha, Anna; Czuj, Tadeusz; Szopa, Jan

    2015-01-01

    Inflammation is the basis of many diseases, with chronic wounds amongst them, limiting cell proliferation and tissue regeneration. Our previous preclinical study of flax fiber applied as a wound dressing and analysis of its components impact on the fibroblast transcriptome suggested flax fiber hydrophobic extract use as an anti-inflammatory and wound healing preparation. The extract contains cannabidiol (CBD), phytosterols, and unsaturated fatty acids, showing great promise in wound healing. In in vitro proliferation and wound closure tests the extract activated cell migration and proliferation. The activity of matrix metalloproteinases in skin cells was increased, suggesting activation of extracellular components remodeling. The expression of cytokines was diminished by the extract in a cannabidiol-dependent manner, but β-sitosterol can act synergistically with CBD in inflammation inhibition. Extracellular matrix related genes were also analyzed, considering their importance in further stages of wound healing. The extract activated skin cell matrix remodeling, but the changes were only partially cannabidiol- and β-sitosterol-dependent. The possible role of fatty acids also present in the extract is suggested. The study shows the hydrophobic flax fiber components as wound healing activators, with anti-inflammatory cannabidiol acting in synergy with sterols, and migration and proliferation promoting agents, some of which still require experimental identification. PMID:26347154

  20. Flax Fiber Hydrophobic Extract Inhibits Human Skin Cells Inflammation and Causes Remodeling of Extracellular Matrix and Wound Closure Activation.

    PubMed

    Styrczewska, Monika; Kostyn, Anna; Kulma, Anna; Majkowska-Skrobek, Grazyna; Augustyniak, Daria; Prescha, Anna; Czuj, Tadeusz; Szopa, Jan

    2015-01-01

    Inflammation is the basis of many diseases, with chronic wounds amongst them, limiting cell proliferation and tissue regeneration. Our previous preclinical study of flax fiber applied as a wound dressing and analysis of its components impact on the fibroblast transcriptome suggested flax fiber hydrophobic extract use as an anti-inflammatory and wound healing preparation. The extract contains cannabidiol (CBD), phytosterols, and unsaturated fatty acids, showing great promise in wound healing. In in vitro proliferation and wound closure tests the extract activated cell migration and proliferation. The activity of matrix metalloproteinases in skin cells was increased, suggesting activation of extracellular components remodeling. The expression of cytokines was diminished by the extract in a cannabidiol-dependent manner, but β-sitosterol can act synergistically with CBD in inflammation inhibition. Extracellular matrix related genes were also analyzed, considering their importance in further stages of wound healing. The extract activated skin cell matrix remodeling, but the changes were only partially cannabidiol- and β-sitosterol-dependent. The possible role of fatty acids also present in the extract is suggested. The study shows the hydrophobic flax fiber components as wound healing activators, with anti-inflammatory cannabidiol acting in synergy with sterols, and migration and proliferation promoting agents, some of which still require experimental identification. PMID:26347154

  1. Flax Fiber Hydrophobic Extract Inhibits Human Skin Cells Inflammation and Causes Remodeling of Extracellular Matrix and Wound Closure Activation.

    PubMed

    Styrczewska, Monika; Kostyn, Anna; Kulma, Anna; Majkowska-Skrobek, Grazyna; Augustyniak, Daria; Prescha, Anna; Czuj, Tadeusz; Szopa, Jan

    2015-01-01

    Inflammation is the basis of many diseases, with chronic wounds amongst them, limiting cell proliferation and tissue regeneration. Our previous preclinical study of flax fiber applied as a wound dressing and analysis of its components impact on the fibroblast transcriptome suggested flax fiber hydrophobic extract use as an anti-inflammatory and wound healing preparation. The extract contains cannabidiol (CBD), phytosterols, and unsaturated fatty acids, showing great promise in wound healing. In in vitro proliferation and wound closure tests the extract activated cell migration and proliferation. The activity of matrix metalloproteinases in skin cells was increased, suggesting activation of extracellular components remodeling. The expression of cytokines was diminished by the extract in a cannabidiol-dependent manner, but β-sitosterol can act synergistically with CBD in inflammation inhibition. Extracellular matrix related genes were also analyzed, considering their importance in further stages of wound healing. The extract activated skin cell matrix remodeling, but the changes were only partially cannabidiol- and β-sitosterol-dependent. The possible role of fatty acids also present in the extract is suggested. The study shows the hydrophobic flax fiber components as wound healing activators, with anti-inflammatory cannabidiol acting in synergy with sterols, and migration and proliferation promoting agents, some of which still require experimental identification.

  2. Food matrix and processing influence on carotenoid bioaccessibility and lipophilic antioxidant activity of fruit juice-based beverages.

    PubMed

    Rodríguez-Roque, María Janeth; de Ancos, Begoña; Sánchez-Vega, Rogelio; Sánchez-Moreno, Concepción; Cano, M Pilar; Elez-Martínez, Pedro; Martín-Belloso, Olga

    2016-01-01

    The biological activity of carotenoids depends on their bioaccessibility and solubilization in the gastrointestinal tract. These compounds are poorly dispersed in the aqueous media of the digestive tract due to their lipophilic nature. Thus, it is important to analyze the extent to which some factors, such as the food matrix and food processing, may improve their bioaccessibility. Beverages formulated with a blend of fruit juices and water (WB), milk (MB) or soymilk (SB) were treated by high-intensity pulsed electric fields (HIPEF) (35 kV cm(-1) with 4 μs bipolar pulses at 200 Hz for 1800 μs), high-pressure processing (HPP) (400 MPa at 40 °C for 5 min) or thermal treatment (TT) (90 °C for 1 min) in order to evaluate the influence of food matrix and processing on the bioaccessibility of carotenoids and on the lipophilic antioxidant activity (LAA). The bioaccessibility of these compounds diminished after applying any treatment (HIPEF, HPP and TT), with the exception of cis-violaxanthin + neoxanthin, which increased by 79% in HIPEF and HPP beverages. The lowest carotenoid bioaccessibility was always obtained in TT beverages (losses up to 63%). MB was the best food matrix for improving the bioaccessibility of carotenoids, as well as the LAA. The results demonstrate that treatment and food matrix modulated the bioaccessibility of carotenoids as well as the lipophilic antioxidant potential of beverages. Additionally, HIPEF and HPP could be considered as promising technologies to obtain highly nutritional and functional beverages.

  3. A novel peptide-modified and gene-activated biomimetic bone matrix accelerating bone regeneration.

    PubMed

    Pan, Haitao; Zheng, Qixin; Yang, Shuhua; Guo, Xiaodong; Wu, Bin; Zou, Zhenwei; Duan, Zhixia

    2014-08-01

    The osteogenic differentiation of bone marrow stromal cells (BMSCs) can be regulated by systemic or local growth factor, especially by transforming growth factor beta 1 (TGF-β1). However, how to maintain the bioactivity of exogenous TGF-β1 is a great challenge due to its short half-life time. The most promising solution is to transfer TGF-β1 gene into seed cells through transgenic technology and then transgenic cells to continuously secret endogenous TGF-β1 protein via gene expression. In this study, a novel non-viral vector (K)16GRGDSPC was chemically linked to bioactive bone matrices PLGA-[ASP-PEG]n using cross-linker to construct a novel non-viral gene transfer system. TGF-β1 gene was incubated with this system and subsequently rabbit-derived BMSCs were co-cultured with this gene-activated PLGA-[ASP-PEG]n, while co-cultured with PLGA-[ASP-PEG]n modified with (K)16GRGDSPC only and original PLGA-[ASP-PEG]n as control. Thus we fabricated three kinds of composites: Group A (BMSCs-TGF-β1DNA-(K)16GRGDSPC-PLGA-[ASP-PEG]n composite); Group B (BMSCs-(K)16GRGDSPC-PLGA-[ASP-PEG]n composite); and Group C (BMSCs-PLGA-[ASP-PEG]n composite). TGF-β1 and other osteogenic phenotype markers of alkaline phosphatase, osteocalcin, osteopontin and type I collagen in Group A were all significantly higher than the other two groups ex vivo. In vivo, 15-mm long segmental rabbit bone defects were created and randomly implanted the aforementioned composites separately, and then fixed with plate-screws. The results demonstrated that the implants in Group A significantly accelerated bone regeneration compared with the other implants based on X-rays, histological and biomechanical examinations. Therefore, we conclude this novel peptide-modified and gene-activated biomimetic bone matrix of TGF-β1DNA-(K)16GRGDSPC-PLGA-[ASP-PEG]n is a very promising scaffold biomaterial for accelerating bone regeneration. PMID:24115366

  4. Improved Readout For Micromagnet/Hall-Effect Memories

    NASA Technical Reports Server (NTRS)

    Wu, Jiin-Chuan; Stadler, Henry L.; Katti, Romney R.

    1993-01-01

    Two improved readout circuits for micromagnet/Hall-effect random-access memories designed to eliminate current shunts introducing errors into outputs of older readout circuits. Incorporate additional switching transistors to isolate Hall sensors as needed.

  5. PANDA straw tube detectors and readout

    NASA Astrophysics Data System (ADS)

    Strzempek, P.

    2016-07-01

    PANDA is a detector under construction dedicated to studies of production and interaction of particles in the charmonium mass range using antiproton beams in the momentum range of 1.5 - 15 GeV/c at the Facility for Antiproton and Ion Research (FAIR) in Darmstadt. PANDA consists of two spectrometers: a Target Spectrometer with a superconducting solenoid and a Forward Spectrometer using a large dipole magnet and covering the most forward angles (Θ < 10 °). In both spectrometers, the particle's trajectories in the magnetic field are measured using self-supporting straw tube detectors. The expected high count rates, reaching up to 1 MHz/straw, are one of the main challenges for the detectors and associated readout electronics. The paper presents the readout chain of the tracking system and the results of tests performed with realistic prototype setups. The readout chain consists of a newly developed ASIC chip (PASTTREC < PANDASTTReadoutChip >) with amplification, signal shaping, tail cancellation, discriminator stages and Time Readout Boards as digitizer boards.

  6. Microwave multiplex readout for superconducting sensors

    NASA Astrophysics Data System (ADS)

    Ferri, E.; Becker, D.; Bennett, D.; Faverzani, M.; Fowler, J.; Gard, J.; Giachero, A.; Hays-Wehle, J.; Hilton, G.; Maino, M.; Mates, J.; Puiu, A.; Nucciotti, A.; Reintsema, C.; Schmidt, D.; Swetz, D.; Ullom, J.; Vale, L.

    2016-07-01

    The absolute neutrino mass scale is still an outstanding challenge in both particle physics and cosmology. The calorimetric measurement of the energy released in a nuclear beta decay is a powerful tool to determine the effective electron-neutrino mass. In the last years, the progress on low temperature detector technologies has allowed to design large scale experiments aiming at pushing down the sensitivity on the neutrino mass below 1 eV. Even with outstanding performances in both energy (~ eV on keV) and time resolution (~ 1 μs) on the single channel, a large number of detectors working in parallel is required to reach a sub-eV sensitivity. Microwave frequency domain readout is the best available technique to readout large array of low temperature detectors, such as Transition Edge Sensors (TESs) or Microwave Kinetic Inductance Detectors (MKIDs). In this way a multiplex factor of the order of thousands can be reached, limited only by the bandwidth of the available commercial fast digitizers. This microwave multiplexing system will be used to readout the HOLMES detectors, an array of 1000 microcalorimeters based on TES sensors in which the 163Ho will be implanted. HOLMES is a new experiment for measuring the electron neutrino mass by means of the electron capture (EC) decay of 163Ho. We present here the microwave frequency multiplex which will be used in the HOLMES experiment and the microwave frequency multiplex used to readout the MKID detectors developed in Milan as well.

  7. Raman-based microarray readout: a review.

    PubMed

    Haisch, Christoph

    2016-07-01

    For a quarter of a century, microarrays have been part of the routine analytical toolbox. Label-based fluorescence detection is still the commonest optical readout strategy. Since the 1990s, a continuously increasing number of label-based as well as label-free experiments on Raman-based microarray readout concepts have been reported. This review summarizes the possible concepts and methods and their advantages and challenges. A common label-based strategy is based on the binding of selective receptors as well as Raman reporter molecules to plasmonic nanoparticles in a sandwich immunoassay, which results in surface-enhanced Raman scattering signals of the reporter molecule. Alternatively, capture of the analytes can be performed by receptors on a microarray surface. Addition of plasmonic nanoparticles again leads to a surface-enhanced Raman scattering signal, not of a label but directly of the analyte. This approach is mostly proposed for bacteria and cell detection. However, although many promising readout strategies have been discussed in numerous publications, rarely have any of them made the step from proof of concept to a practical application, let alone routine use. Graphical Abstract Possible realization of a SERS (Surface-Enhanced Raman Scattering) system for microarray readout. PMID:26973235

  8. Development of a pixel readout chip for BTeV

    SciTech Connect

    D.C. Christian et al.

    1998-11-01

    A description is given of the R&D program underway at Fermilab to develop a pixel readout ASIC appropriate for use at the Tevatron collider. Results are presentetd frOm tests performed on the first prototype pixel readout chip deigned at Fermilab, and a new readout architecture is described.

  9. Development of arrays of Silicon Drift Detectors and readout ASIC for the SIDDHARTA experiment

    NASA Astrophysics Data System (ADS)

    Quaglia, R.; Schembari, F.; Bellotti, G.; Butt, A. D.; Fiorini, C.; Bombelli, L.; Giacomini, G.; Ficorella, F.; Piemonte, C.; Zorzi, N.

    2016-07-01

    This work deals with the development of new Silicon Drift Detectors (SDDs) and readout electronics for the upgrade of the SIDDHARTA experiment. The detector is based on a SDDs array organized in a 4×2 format with each SDD square shaped with 64 mm2 (8×8) active area. The total active area of the array is therefore 32×16 mm2 while the total area of the detector (including 1 mm border dead area) is 34 × 18mm2. The SIDDHARTA apparatus requires 48 of these modules that are designed and manufactured by Fondazione Bruno Kessler (FBK). The readout electronics is composed by CMOS preamplifiers (CUBEs) and by the new SFERA (SDDs Front-End Readout ASIC) circuit. SFERA is a 16-channels readout ASIC designed in a 0.35 μm CMOS technology, which features in each single readout channel a high order shaping amplifier (9th order Semi-Gaussian complex-conjugate poles) and a high efficiency pile-up rejection logic. The outputs of the channels are connected to an analog multiplexer for the external analog to digital conversion. An on-chip 12-bit SAR ADC is also included. Preliminary measurements of the detectors in the single SDD format are reported. Also measurements of low X-ray energies are reported in order to prove the possible extension to the soft X-ray range.

  10. A Novel Intracellular Isoform of Matrix Metalloproteinase-2 Induced by Oxidative Stress Activates Innate Immunity

    PubMed Central

    Lovett, David H.; Mahimkar, Rajeev; Raffai, Robert L.; Cape, Leslie; Maklashina, Elena; Cecchini, Gary; Karliner, Joel S.

    2012-01-01

    Background Experimental and clinical evidence has pinpointed a critical role for matrix metalloproteinase-2 (MMP-2) in ischemic ventricular remodeling and systolic heart failure. Prior studies have demonstrated that transgenic expression of the full-length, 68 kDa, secreted form of MMP-2 induces severe systolic failure. These mice also had unexpected and severe mitochondrial structural abnormalities and dysfunction. We hypothesized that an additional intracellular isoform of MMP-2, which affects mitochondrial function is induced under conditions of systolic failure-associated oxidative stress. Methodology and Principal Findings Western blots of cardiac mitochondria from the full length MMP-2 transgenics, ageing mice and a model of accelerated atherogenesis revealed a smaller 65 kDa MMP-2 isoform. Cultured cardiomyoblasts subjected to transient oxidative stress generated the 65 kDa MMP-2 isoform. The 65 kDa MMP-2 isoform was also induced by hypoxic culture of cardiomyoblasts. Genomic database analysis of the MMP-2 gene mapped transcriptional start sites and RNA transcripts induced by hypoxia or epigenetic modifiers within the first intron of the MMP-2 gene. Translation of these transcripts yields a 65 kDa N-terminal truncated isoform beginning at M77, thereby deleting the signal sequence and inhibitory prodomain. Cellular trafficking studies demonstrated that the 65 kDa MMP-2 isoform is not secreted and is present in cytosolic and mitochondrial fractions, while the full length 68 kDa isoform was found only in the extracellular space. Expression of the 65 kDa MMP-2 isoform induced mitochondrial-nuclear stress signaling with activation of the pro-inflammatory NF-κB, NFAT and IRF transcriptional pathways. By microarray, the 65 kDa MMP-2 induces an innate immunity transcriptome, including viral stress response genes, innate immunity transcription factor IRF7, chemokines and pro-apoptosis genes. Conclusion A novel N-terminal truncated intracellular isoform of MMP-2 is

  11. Planarization coating for polyimide substrates used in roll-to-roll fabrication of active matrix backplanes for flexible displays

    NASA Astrophysics Data System (ADS)

    Almanza-Workman, A. Marcia; Jeans, Albert; Braymen, Steve; Elder, Richard E.; Garcia, Robert A.; de la Fuente Vornbrock, Alejandro; Hauschildt, Jason; Holland, Edward; Jackson, Warren; Jam, Mehrban; Jeffrey, Frank; Junge, Kelly; Kim, Han-Jun; Kwon, Ohseung; Larson, Don; Luo, Hao; Maltabes, John; Mei, Ping; Perlov, Craig; Smith, Mark; Stieler, Dan; Taussig, Carl P.; Trovinger, Steve; Zhao, Lihua

    2012-03-01

    Good surface quality of plastic substrates is essential to reduce pixel defects during roll-to-roll fabrication of flexible display active matrix backplanes. Standard polyimide substrates have a high density of "bumps" from fillers and belt marks and other defects from dust and surface scratching. Some of these defects could be the source of shunts in dielectrics. The gate dielectric must prevent shorts between the source/drain and the gate in the transistors, resist shorts in the hold capacitor and stop shorts in the data/gate line crossovers in active matrix backplanes fabricated by self-aligned imprint lithography (SAIL) roll-to-roll processes. Otherwise data and gate lines will become shorted creating line or pixel defects. In this paper, we discuss the development of a proprietary UV curable planarization material that can be coated by roll-to-roll processes. This material was engineered to have low shrinkage, excellent adhesion to polyimide, high dry etch resistance, and great chemical and thermal stability. Results from PECVD deposition of an amorphous silicon stack on the planarized polyimide and compatibility with roll-to-roll processes to fabricate active matrix backplanes are also discussed. The effect of the planarization on defects in the stack, shunts in the dielectric and curvature of finished arrays will also be described.

  12. Roles of mitogen activated protein kinases and EGF receptor in arsenite-stimulated matrix metalloproteinase-9 production

    SciTech Connect

    Cooper, Karen L.; Myers, Terrance Alix; Rosenberg, Martina; Chavez, Miquella; Hudson, Laurie G. . E-mail: lghudson@unm.edu

    2004-11-01

    The dermatotoxicity of arsenic is well established and epidemiological studies identify an increased incidence of keratinocytic tumors (basal cell and squamous cell carcinoma) associated with arsenic exposure. Little is known about the underlying mechanisms of arsenic-mediated skin carcinogenesis, but activation of mitogen-activated protein (MAP) kinases and subsequent regulation of downstream target genes may contribute to tumor promotion and progression. In this study, we investigated activation of the extracellular signal regulated kinase (ERK) and the stress-associated kinase p38 by arsenite in HaCat cells, a spontaneously immortalized human keratinocyte cell line. Arsenite concentrations {>=}100 {mu}M stimulate rapid activation of p38 and ERK MAP kinases. However, upon extended exposure (24 h), persistent stimulation of p38 and ERK MAP kinases was detected at low micromolar concentrations of arsenite. Although ERK and p38 were activated with similar time and concentration dependence, the mechanism of activation differed for these two MAP kinases. ERK activation by arsenite was fully dependent on the catalytic activity of the epidermal growth factor (EGF) receptor and partially dependent on Src-family kinase activity. In contrast, p38 activation was independent of EGF receptor or Src-family kinase activity. Arsenite-stimulated MAP kinase signal transduction resulted in increased production of matrix metalloproteinase (MMP)-9, an AP-1 regulated gene product. MMP-9 induction by arsenite was prevented when EGF receptor or MAP kinase signaling was inhibited. These studies indicate that EGF receptor activation is a component of arsenite-mediated signal transduction and gene expression in keratinocytes and that low micromolar concentrations of arsenite stimulate key signaling pathways upon extended exposure. Stimulation of MAP kinase cascades by arsenic and subsequent regulation of genes including c-fos, c-jun, and the matrix degrading proteases may play an important

  13. Back-side-illuminated 1.4μm pixel with a vertically pinned photodiode based on hole collection, PMOS readout chain and active side-wall passivation

    NASA Astrophysics Data System (ADS)

    Mamdy, Bastien; Roy, François; Ahmed, Nayera; Lu, Guo-Neng

    2015-10-01

    To further improve the characteristics of CMOS image sensors (CIS), we propose a back-side illuminated pixel integrating a vertically pinned and P-type photodiode (which collects holes) and PMOS readout circuitry. It has been designed in a 1.4μm-pitch, a two-transistor (2T) shared readout architecture and fabricated in a combined 65nm and 90nm technology. The vertically pinned photodiode takes up almost the entire volume of the pixel, allowing a full well capacity (FWC) exceeding 7000h+. With a conversion factor around 120μV/h+, the output swing approaching 1V is achieved on the column voltage. The pixel also integrates capacitive deep trench isolation (CDTI) to tackle electrical and optical crosstalk issues. The effective passivation of trench interface by CDTI bias control is demonstrated for a hole-based pixel. As expected, PMOS transistors have much lower trapping noise compared to NMOS counterparts. The PMOS source follower has an average temporal noise of 195μV, mainly dominated by thermal noise contribution.

  14. Matrix metallopeptidase 2 activity in tendon regions: effects of mechanical loading exercise associated to anabolic-androgenic steroids.

    PubMed

    Marqueti, Rita C; Prestes, Jonato; Paschoal, Milena; Ramos, Oscar H P; Perez, Sérgio E A; Carvalho, Hernandes F; Selistre-de-Araujo, Heloisa S

    2008-12-01

    Matrix metallopeptidases (MMPs) are responsible for degradation of the extracellular matrix components and tissue remodeling. To achieve a better understanding of AAS effects in rat tendon, MMP-2 activity in the proximal and distal regions of the calcanear tendon (CT) and proximal, intermediate and distal region of superficial (SFT) and deep flexor tendons (DFT) after mechanical load exercise associated with AAS was investigated. Animals were grouped into four groups: sedentary animals (S); sedentary animals with ASS supplementation (S + A); trained animals (T) and trained animals with AAS supplementation (T + A). Analysis of MMP activity in tendon extracts was done by gelatin zymography. Both proximal and distal regions of the calcanear tendon showed the lowest MMP-2 concentration and the highest proportion in MMP-2 active form. The intermediate region of the SFT differed (P < 0.01) from the proximal and distal regions with higher % of active MMP-2 in the sedentary group. The proportion of active MMP-2 decreased in the proximal region of the CT. AAS treatment strongly decreased both MMP-2 concentration and active form in the three regions of the SFT and on the proximal region of the CT, but not on the DFT. The differences in the response to exercise and AAS treatment are a result of distinct metabolism and recruitment of these tendon regions in the exercise program employed in this study.

  15. Aryl Hydrocarbon Receptor Activation by TCDD Modulates Expression of Extracellular Matrix Remodeling Genes during Experimental Liver Fibrosis

    PubMed Central

    Lamb, Cheri L.; Cholico, Giovan N.; Perkins, Daniel E.; Fewkes, Michael T.; Oxford, Julia Thom; Lujan, Trevor J.; Morrill, Erica E.

    2016-01-01

    The aryl hydrocarbon receptor (AhR) is a soluble, ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Increasing evidence implicates the AhR in regulating extracellular matrix (ECM) homeostasis. We recently reported that TCDD increased necroinflammation and myofibroblast activation during liver injury elicited by carbon tetrachloride (CCl4). However, TCDD did not increase collagen deposition or exacerbate fibrosis in CCl4-treated mice, which raises the possibility that TCDD may enhance ECM turnover. The goal of this study was to determine how TCDD impacts ECM remodeling gene expression in the liver. Male C57BL/6 mice were treated for 8 weeks with 0.5 mL/kg CCl4, and TCDD (20 μg/kg) was administered during the last two weeks. Results indicate that TCDD increased mRNA levels of procollagen types I, III, IV, and VI and the collagen processing molecules HSP47 and lysyl oxidase. TCDD also increased gelatinase activity and mRNA levels of matrix metalloproteinase- (MMP-) 3, MMP-8, MMP-9, and MMP-13. Furthermore, TCDD modulated expression of genes in the plasminogen activator/plasmin system, which regulates MMP activation, and it also increased TIMP1 gene expression. These findings support the notion that AhR activation by TCDD dysregulates ECM remodeling gene expression and may facilitate ECM metabolism despite increased liver injury.

  16. Aryl Hydrocarbon Receptor Activation by TCDD Modulates Expression of Extracellular Matrix Remodeling Genes during Experimental Liver Fibrosis

    PubMed Central

    Lamb, Cheri L.; Cholico, Giovan N.; Perkins, Daniel E.; Fewkes, Michael T.; Oxford, Julia Thom; Lujan, Trevor J.; Morrill, Erica E.

    2016-01-01

    The aryl hydrocarbon receptor (AhR) is a soluble, ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Increasing evidence implicates the AhR in regulating extracellular matrix (ECM) homeostasis. We recently reported that TCDD increased necroinflammation and myofibroblast activation during liver injury elicited by carbon tetrachloride (CCl4). However, TCDD did not increase collagen deposition or exacerbate fibrosis in CCl4-treated mice, which raises the possibility that TCDD may enhance ECM turnover. The goal of this study was to determine how TCDD impacts ECM remodeling gene expression in the liver. Male C57BL/6 mice were treated for 8 weeks with 0.5 mL/kg CCl4, and TCDD (20 μg/kg) was administered during the last two weeks. Results indicate that TCDD increased mRNA levels of procollagen types I, III, IV, and VI and the collagen processing molecules HSP47 and lysyl oxidase. TCDD also increased gelatinase activity and mRNA levels of matrix metalloproteinase- (MMP-) 3, MMP-8, MMP-9, and MMP-13. Furthermore, TCDD modulated expression of genes in the plasminogen activator/plasmin system, which regulates MMP activation, and it also increased TIMP1 gene expression. These findings support the notion that AhR activation by TCDD dysregulates ECM remodeling gene expression and may facilitate ECM metabolism despite increased liver injury. PMID:27672655

  17. A new interpolation arithmetic based readout signals process method for infrared imaging system applications

    NASA Astrophysics Data System (ADS)

    Li, Xinyi; Yao, Suying; Zhao, Yiqiang

    2009-07-01

    A new readout signals process circuit for infrared focal plane array (IR FPA) applications is proposed. In the proposed structure the continuous-time current signals from the detector array are mirrored, amplified, integrated on the integration capacitors and changed to discrete analog voltage signals. Next, these voltage signals are amplified and modulated by a group of encoded signals from the column buses, then fed to a multiple-input analog adder to generate a single serial output data stream. The generated single serial data stream is transferred to the mitigate noise circuit and is converted to digital signals by the A/D converter. For very large format detector arrays applications the speed restriction of the time-multiplexing circuitry and the A/D converter will be released. Since no scan technique has been used, all the output signals from an entire row in the detector array have been readout simultaneously without loss of optical power, the scalability of the photon-signals, the readout efficiency and the accuracy of the imaging system will be improved. Theory analysis and experimental results show that the proposed idea is reasonable and efficient. The proposed readout method is a solid option for large format infrared detector arrays and highly integrated infrared imaging system applications. In addition, the proposed idea also can be used for other active and passive imaging readout integrated circuits.

  18. Readout architecture for sub-nanosecond resolution TDC

    NASA Astrophysics Data System (ADS)

    Marteau, J.; Carlus, B.; Gardien, S.; Girerd, C.; Ianigro, J.-C.; Montorio, J.-L.; Gibert, D.; Nicollin, F.

    2012-04-01

    The DIAPHANE project is pluri-disciplinary collaboration between particle physicists and geophysicists to perform the tomography of large geological structure mainly devoted to the study of active volcanoes. The detector used for this tomography, hereafter referred to as telescope, uses a standard, robust, cost-effective and well-known technology based on solid plastic scintillator readout by photomultiplier(s) (either multichannel pixelized PM or silicon PM). The electronics system is built on the concept of autonomous, triggerless, smart sensor directly connected on a standard fast Ethernet network. First radiographies have been performed on the Mont-Terri underground laboratory (St-Ursanne, Switzerland) and on the active volcano of La Soufrière (Guadeloupe, Lesser Antilles, France). We present an upgrade of the readout architecture allowing to embed a sub-nanosecond resolution TDC within the existing programmable logic to help in the background rejection (rear flux, random coincidences) and to improve the detection purity and the radiography quality. First results obtained are also presented and briefly discussed.

  19. Matrix-M™ Adjuvant Induces Local Recruitment, Activation and Maturation of Central Immune Cells in Absence of Antigen

    PubMed Central

    Reimer, Jenny M.; Karlsson, Karin H.; Lövgren-Bengtsson, Karin; Magnusson, Sofia E.; Fuentes, Alexis; Stertman, Linda

    2012-01-01

    Saponin-based adjuvants are widely used to enhance humoral and cellular immune responses towards vaccine antigens, although it is not yet completely known how they mediate their stimulatory effects. The aim of this study was to elucidate the mechanism of action of adjuvant Matrix-M™ without antigen and Alum was used as reference adjuvant. Adjuvant Matrix-M™ is comprised of 40 nm nanoparticles composed of Quillaja saponins, cholesterol and phospholipid. BALB/c mice were subcutaneously injected once with, 3, 12 or 30 µg of Matrix-M™, resulting in recruitment of leukocytes to draining lymph nodes (dLNs) and spleen 48 h post treatment. Flow cytometry analysis identified CD11b+ Gr-1high granulocytes as the cell population increasing most in dLNs and spleen. Additionally, dendritic cells, F4/80int cells, T-, B- and NK-cells were recruited to dLNs and in spleen the number of F4/80int cells, and to some extent, B cells and dendritic cells, increased. Elevated levels of early activation marker CD69 were detected on T-, B- and NK-cells, CD11b+ Gr-1high cells, F4/80int cells and dendritic cells in dLNs. In spleen CD69 was mainly up-regulated on NK cells. B cells and dendritic cells in dLNs and spleen showed an increased expression of the co-stimulatory molecule CD86 and dendritic cells in dLNs expressed elevated levels of MHC class II. The high-dose (30 µg) of Matrix-M™ induced detectable serum levels of IL-6 and MIP-1β 4 h post administration, most likely representing spillover of locally produced cytokines. A lesser increase of IL-6 in serum after administration of 12 µg Matrix-M™ was also observed. In conclusion, early immunostimulatory properties were demonstrated by Matrix-M™ alone, as therapeutic doses resulted in a local transient immune response with recruitment and activation of central immune cells to dLNs. These effects may play a role in enhancing uptake and presentation of vaccine antigens to elicit a competent immune response. PMID:22844480

  20. Inducible Nitric Oxide Synthase Deficiency Impairs Matrix Metalloproteinase-9 Activity and Disrupts Leukocyte Migration in Hepatic Ischemia/Reperfusion Injury

    PubMed Central

    Hamada, Takashi; Duarte, Sergio; Tsuchihashi, Seiichiro; Busuttil, Ronald W.; Coito, Ana J.

    2009-01-01

    Matrix metalloproteinase 9 (MMP-9) is a critical mediator of leukocyte migration in hepatic ischemia/reperfusion (I/R) injury. To test the relevance of inducible nitric oxide synthase (iNOS) expression on the regulation of MMP-9 activity in liver I/R injury, our experiments included both iNOS-deficient mice and mice treated with ONO-1714, a specific iNOS inhibitor. The inability of iNOS-deficient mice to generate iNOS-derived nitric oxide (NO) profoundly inhibited MMP-9 activity and depressed leukocyte migration in livers after I/R injury. While macrophages expressed both iNOS and MMP-9 in damaged wild-type livers, neutrophils expressed MMP-9 and were virtually negative for iNOS; however, exposure of isolated murine neutrophils and macrophages to exogenous NO increased MMP-9 activity in both cell types, suggesting that NO may activate MMP-9 in leukocytes by either autocrine or paracrine mechanisms. Furthermore, macrophage NO production through the induction of iNOS was capable of promoting neutrophil transmigration across fibronectin in a MMP-9-dependent manner. iNOS expression in liver I/R injury was also linked to liver apoptosis, which was reduced in the absence of MMP-9. These results suggest that MMP-9 activity induced by iNOS-derived NO may also lead to detachment of hepatocytes from the extracellular matrix and cell death, in addition to regulating leukocyte migration across extracellular matrix barriers. These data provide evidence for a novel mechanism by which MMP-9 can mediate iNOS-induced liver I/R injury. PMID:19443702

  1. How, with whom and when: an overview of CD147-mediated regulatory networks influencing matrix metalloproteinase activity

    PubMed Central

    Grass, G. Daniel; Toole, Bryan P.

    2015-01-01

    Matrix metalloproteinases (MMPs) comprise a family of 23 zinc-dependent enzymes involved in various pathologic and physiologic processes. In cancer, MMPs contribute to processes from tumour initiation to establishment of distant metastases. Complex signalling and protein transport networks regulate MMP synthesis, cell surface presentation and release. Earlier attempts to disrupt MMP activity in patients have proven to be intolerable and with underwhelming clinical efficacy; thus targeting ancillary proteins that regulate MMP activity may be a useful therapeutic approach. Extracellular matrix metalloproteinase inducer (EMMPRIN) was originally characterized as a factor present on lung cancer cells, which stimulated collagenase (MMP-1) production in fibroblasts. Subsequent studies demonstrated that EMMPRIN was identical with several other protein factors, including basigin (Bsg), all of which are now commonly termed CD147. CD147 modulates the synthesis and activity of soluble and membrane-bound [membrane-type MMPs (MT-MMPs)] in various contexts via homophilic/heterophilic cell interactions, vesicular shedding or cell-autonomous processes. CD147 also participates in inflammation, nutrient and drug transporter activity, microbial pathology and developmental processes. Despite the hundreds of manuscripts demonstrating CD147-mediated MMP regulation, the molecular underpinnings governing this process have not been fully elucidated. The present review summarizes our present knowledge of the complex regulatory systems influencing CD147 biology and provides a framework to understand how CD147 may influence MMP activity. PMID:26604323

  2. Biochemical and toxicological evaluation of nano-heparins in cell functional properties, proteasome activation and expression of key matrix molecules.

    PubMed

    Piperigkou, Zoi; Karamanou, Konstantina; Afratis, Nikolaos A; Bouris, Panagiotis; Gialeli, Chrysostomi; Belmiro, Celso L R; Pavão, Mauro S G; Vynios, Dimitrios H; Tsatsakis, Aristidis M

    2016-01-01

    The glycosaminoglycan heparin and its derivatives act strongly on blood coagulation, controlling the activity of serine protease inhibitors in plasma. Nonetheless, there is accumulating evidence highlighting different anticancer activities of these molecules in numerous types of cancer. Nano-heparins may have great biological significance since they can inhibit cell proliferation and invasion as well as inhibiting proteasome activation. Moreover, they can cause alterations in the expression of major modulators of the tumor microenvironment, regulating cancer cell behavior. In the present study, we evaluated the effects of two nano-heparin formulations: one isolated from porcine intestine and the other from the sea squirt Styela plicata, on a breast cancer cell model. We determined whether these nano-heparins are able to affect cell proliferation, apoptosis and invasion, as well as proteasome activity and the expression of extracellular matrix molecules. Specifically, we observed that nano-Styela compared to nano-Mammalian analogue has higher inhibitory role on cell proliferation, invasion and proteasome activity. Moreover, nano-Styela regulates cell apoptosis, expression of inflammatory molecules, such as IL-6 and IL-8 and reduces the expression levels of extracellular matrix macromolecules, such as the proteolytic enzymes MT1-MMP, uPA and the cell surface proteoglycans syndecan-1 and -2, but not on syndecan-4. The observations reported in the present article indicate that nano-heparins and especially ascidian heparin are effective agents for heparin-induced effects in critical cancer cell functions, providing an important possibility in pharmacological targeting.

  3. Supplemental Immobilization of Hanford Low-Activity Waste: Cast Stone Augmented Formulation Matrix Tests

    SciTech Connect

    Cozzi, A.; Crawford, C.; Fox, K.; Hansen, E.; Roberts, K.

    2015-07-20

    More than 56 million gallons of radioactive and hazardous waste are stored in 177 underground storage tanks at the U.S. Department of Energy’s (DOE’s) Hanford Site in Washington State. The HLW will be vitrified in the HLW facility for ultimate disposal at an offsite federal repository. A portion (~35%) of the LAW will be vitrified in the LAW vitrification facility for disposal onsite at the Integrated Disposal Facility (IDF). The pretreatment and HLW vitrification facilities will have the capacity to treat and immobilize all of the wastes destined for those facilities. However, a second facility will be needed for the expected volume of LAW requiring immobilization. Cast Stone, a cementitious waste form, is being considered to provide the required additional LAW immobilization capacity. The Cast Stone waste form must be acceptable for disposal in the IDF. The Cast Stone waste form and immobilization process must be tested to demonstrate that the final Cast Stone waste form can comply with the waste acceptance criteria for the disposal facility and that the immobilization processes can be controlled to consistently provide an acceptable waste form product. A testing program was developed in fiscal year (FY) 2012 describing in detail the work needed to develop and qualify Cast Stone as a waste form for the solidification of Hanford LAW. A statistically designed test matrix was used to evaluate the effects of key parameters on the properties of the Cast Stone as it is initially prepared and after curing. For the processing properties, the water-to-dry-blend mix ratio was the most significant parameter in affecting the range of values observed for each property. The single shell tank (SST) Blend simulant also showed differences in measured properties compared to the other three simulants tested. A review of the testing matrix and results indicated that an additional set of tests would be beneficial to improve the understanding of the impacts noted in the Screening

  4. VCSELs for interferometric readout of MEMS sensors

    NASA Astrophysics Data System (ADS)

    Serkland, Darwin K.; Geib, Kent M.; Peake, Gregory M.; Keeler, Gordon A.; Shaw, Michael J.; Baker, Michael S.; Okandan, Murat

    2016-03-01

    We report on the development of single-frequency VCSELs (vertical-cavity surface-emitting lasers) for sensing the position of a moving MEMS (micro-electro-mechanical system) object with resolution much less than 1nm. Position measurement is the basis of many different types of MEMS sensors, including accelerometers, gyroscopes, and pressure sensors. Typically, by switching from a traditional capacitive electronic readout to an interferometric optical readout, the resolution can be improved by an order of magnitude with a corresponding improvement in MEMS sensor performance. Because the VCSEL wavelength determines the scale of the position measurement, laser wavelength (frequency) stability is desirable. This paper discusses the impact of VCSEL amplitude and frequency noise on the position measurement.

  5. Vector diffraction analysis of optical disk readout.

    PubMed

    Cheng, X; Jia, H; Xu, D

    2000-12-01

    The optical disk readout signals from ROM disks are presented by use of a rigorous three-dimensional vector diffraction method. The optical disk is modeled as a crossed metal grating without restriction on the form of the information marks, and the permittivity of the metal is taken into account. The diffracted field from the disk is obtained by means of decomposing the focused incident beam into a spectrum of plane waves and then calculating the diffracted plane waves for each respective incident component. The readout signal is obtained by integration of the energy-flux density of the diffracted field according to the detection scheme of the optical disk system. A typical digital versatile disk (DVD) system is applied with this theory, and the result is far from that of scalar diffraction theory. PMID:18354657

  6. Indium phosphide-based monolithically integrated PIN waveguide photodiode readout for resonant cantilever sensors

    SciTech Connect

    Siwak, N. P.; Fan, X. Z.; Ghodssi, R.; Kanakaraju, S.; Richardson, C. J. K.

    2014-10-06

    An integrated photodiode displacement readout scheme for a microelectromechanical cantilever waveguide resonator sensing platform is presented. III-V semiconductors are used to enable the monolithic integration of passive waveguides with active optical components. This work builds upon previously demonstrated results by measuring the displacement of cantilever waveguide resonators with on-chip waveguide PIN photodiodes. The on-chip integration of the readout provides an additional 70% improvement in mass sensitivity compared to off-chip photodetector designs due to measurement stability and minimized coupling loss. In addition to increased measurement stability, reduced packaging complexity is achieved due to the simplicity of the readout design. We have fabricated cantilever waveguides with integrated photodetectors and experimentally characterized these cantilever sensors with monolithically integrated PIN photodiodes.

  7. Indium phosphide-based monolithically integrated PIN waveguide photodiode readout for resonant cantilever sensors

    NASA Astrophysics Data System (ADS)

    Siwak, N. P.; Fan, X. Z.; Kanakaraju, S.; Richardson, C. J. K.; Ghodssi, R.

    2014-10-01

    An integrated photodiode displacement readout scheme for a microelectromechanical cantilever waveguide resonator sensing platform is presented. III-V semiconductors are used to enable the monolithic integration of passive waveguides with active optical components. This work builds upon previously demonstrated results by measuring the displacement of cantilever waveguide resonators with on-chip waveguide PIN photodiodes. The on-chip integration of the readout provides an additional 70% improvement in mass sensitivity compared to off-chip photodetector designs due to measurement stability and minimized coupling loss. In addition to increased measurement stability, reduced packaging complexity is achieved due to the simplicity of the readout design. We have fabricated cantilever waveguides with integrated photodetectors and experimentally characterized these cantilever sensors with monolithically integrated PIN photodiodes.

  8. Signal processing for distributed readout using TESs

    NASA Astrophysics Data System (ADS)

    Smith, Stephen J.; Whitford, Chris H.; Fraser, George W.

    2006-04-01

    We describe optimal filtering algorithms for determining energy and position resolution in position-sensitive Transition Edge Sensor (TES) Distributed Read-Out Imaging Devices (DROIDs). Improved algorithms, developed using a small-signal finite-element model, are based on least-squares minimisation of the total noise power in the correlated dual TES DROID. Through numerical simulations we show that significant improvements in energy and position resolution are theoretically possible over existing methods.

  9. LSST camera readout chip ASPIC: test tools

    NASA Astrophysics Data System (ADS)

    Antilogus, P.; Bailly, Ph; Jeglot, J.; Juramy, C.; Lebbolo, H.; Martin, D.; Moniez, M.; Tocut, V.; Wicek, F.

    2012-02-01

    The LSST camera will have more than 3000 video-processing channels. The readout of this large focal plane requires a very compact readout chain. The correlated ''Double Sampling technique'', which is generally used for the signal readout of CCDs, is also adopted for this application and implemented with the so called ''Dual Slope integrator'' method. We have designed and implemented an ASIC for LSST: the Analog Signal Processing asIC (ASPIC). The goal is to amplify the signal close to the output, in order to maximize signal to noise ratio, and to send differential outputs to the digitization. Others requirements are that each chip should process the output of half a CCD, that is 8 channels and should operate at 173 K. A specific Back End board has been designed especially for lab test purposes. It manages the clock signals, digitizes the analog differentials outputs of ASPIC and stores data into a memory. It contains 8 ADCs (18 bits), 512 kwords memory and an USB interface. An FPGA manages all signals from/to all components on board and generates the timing sequence for ASPIC. Its firmware is written in Verilog and VHDL languages. Internals registers permit to define various tests parameters of the ASPIC. A Labview GUI allows to load or update these registers and to check a proper operation. Several series of tests, including linearity, noise and crosstalk, have been performed over the past year to characterize the ASPIC at room and cold temperature. At present, the ASPIC, Back-End board and CCD detectors are being integrated to perform a characterization of the whole readout chain.

  10. Counting rate enhancements in superconducting nanowire single-photon detectors with improved readout circuits.

    PubMed

    Zhao, Qingyuan; Jia, Tao; Gu, Min; Wan, Chao; Zhang, Labao; Xu, Weiwei; Kang, Lin; Chen, Jian; Wu, Peiheng

    2014-04-01

    Counting rates of superconducting nanowire single-photon detectors are usually estimated at hundreds of MHz by their kinetic-inductive reset time. This maximum is also limited by capacitor coupling effects in conventional readout circuits. In this Letter, we design and demonstrate an improved readout circuit that reduces the reset time and removes circuit limits. The counting rate at the 3 dB compression point is increased by four times for a large active area detector. We also discuss nonlinear dependences of the counting rate on the incident continuous-wave optical power and give a numerical model to explain our observations.

  11. Readout Electronics for Hyper Suprime-Cam

    NASA Astrophysics Data System (ADS)

    Miyatake, Hironao; Aihara, Hiroaki; Fujimori, Hiroki; Mineo, Sogo; Miyazaki, Satoshi; Nakaya, Hidehiko; Uchida, Tomohisa

    Hyper Suprime-Cam(HSC)isa1GigapixelCCD camerafora wide-fieldgalaxy surveyatthe Subaru8-mTelescope. It will be mounted on the prime focus of the SubaruTelescope and is scheduled to receive its first light in 2012. The primary science is to conduct a weak lensing survey over ∼ 2,000 square degrees. The HSC has a 1.5-degree-diameter fieldofview, 7timeslarger than thatofits predecessor Suprime-Cam.It consistsofalarge corrector lens systemand afocalplane equippedwith116piecesof2kx4kfully depletedCCDs. Combinedwiththesuperbimagequalityand large aperture of the Subaru telescope, the surveyusing HSC can cover a cosmological volume and reach the limiting magnitude of at least one magnitudefainter than the other surveys conducted using 4-m class telescopes. The readout electronics of the HSC consist of two parts: one is the analog front-end electronics (FEE) and the other is the digital back-end electronics (BEE). The FEE is placed in a vacuum dewar together with the CCDs, and processes the analog CCD signal into 16-bit digital data. The BEE is small and light enough to be integrated into the camera unit, and employs three linksofGigabit Ethernetto readouta 2.3-GByte singleexposure within10 secondsatfast readout operation. The readout noise from the electronics is smaller than that from CCDs.

  12. EMIR high-dynamic range readout modes

    NASA Astrophysics Data System (ADS)

    Nuñez, Miguel; Gago, Fernando; Garzón, Francisco; Díaz, José J.; Barreto, Mary; Patrón, Jesús; González-Fenández, Carlos; Hammersley, Peter L.; López, Luis; Castro, Nieves

    2012-07-01

    EMIR is the NIR imager and multiobject spectrograph being built as a common user instrument for the GTC and it is currently entering in the integration and verification phase at system level. EMIR is being built by a Consortium of Spanish and French institutes led by the IAC. In this paper we describe the readout modes of EMIR detector, a Hawaii2 FPA, after two full calibrations campaigns. Besides the standard set of modes (reset-read, CDS, Fowler, Follow-up the ramp), the modified SDSU-III hardware and home made software will also offer high dynamic range readout modes, which will improve the ability of the instrument to sound densely populated areas which often are made of objects with large differences in brightness. These new high dynamic range modes are: single readout with very short integration time, window mode and combination of both. The results show that the new modes behave linearly with different exposition times, improve the maximum frame rate and increase the saturation limit in image mode for EMIR instrument.

  13. Study of spacecraft direct readout meteorological systems

    NASA Technical Reports Server (NTRS)

    Bartlett, R.; Elam, W.; Hoedemaker, R.

    1973-01-01

    Characteristics are defined of the next generation direct readout meteorological satellite system with particular application to Tiros N. Both space and ground systems are included. The recommended space system is composed of four geosynchronous satellites and two low altitude satellites in sun-synchronous orbit. The goesynchronous satellites transmit to direct readout ground stations via a shared S-band link, relayed FOFAX satellite cloud cover pictures (visible and infrared) and weather charts (WEFAX). Basic sensor data is transmitted to regional Data Utilization Stations via the same S-band link. Basic sensor data consists of 0.5 n.m. sub-point resolution data in the 0.55 - 0.7 micron spectral region, and 4.0 n.m. resolution data in the 10.5 - 12.6 micron spectral region. The two low altitude satellites in sun-synchronous orbit provide data to direct readout ground stations via a 137 MHz link, a 400 Mhz link, and an S-band link.

  14. Qubit readout with the Josephson Photomultiplier

    NASA Astrophysics Data System (ADS)

    Ribeill, Guilhem

    Recent demonstrations of error correction in many qubit circuits, as well as efforts to build a logical qubit, have shown the need for a simple and scalable superconducting quantum bit (qubit) readout. Current solutions based on heterodyne detection and cryogenic amplification of microwave readout tones may prove difficult to scale, while photon counting presents an attractive alternative. However, the development of counters operating at these frequencies has proved technically challenging. In this thesis, we describe the development of the Josephson Photomultiplier (JPM), a microwave photon counting circuit. We discuss the JPM theoretically, and describe the fabrication of the JPM using standard thin film lithography techniques. We measure its properties as a microwave photon counter using a qubit as an in-situ calibrated source of photons. We measure a JPM quantum efficiency at the few percent level. We then use the JPM to perform readout of a transmon qubit in both the dispersive and bright regimes. We observe raw measurement fidelities of 35% and 62% respectively. We discuss how the JPM and measurement protocol could be further optimized to achieve fidelities in excess of 90%.

  15. Embedded controller for GEM detector readout system

    NASA Astrophysics Data System (ADS)

    Zabołotny, Wojciech M.; Byszuk, Adrian; Chernyshova, Maryna; Cieszewski, Radosław; Czarski, Tomasz; Dominik, Wojciech; Jakubowska, Katarzyna L.; Kasprowicz, Grzegorz; Poźniak, Krzysztof; Rzadkiewicz, Jacek; Scholz, Marek

    2013-10-01

    This paper describes the embedded controller used for the multichannel readout system for the GEM detector. The controller is based on the embedded Mini ITX mainboard, running the GNU/Linux operating system. The controller offers two interfaces to communicate with the FPGA based readout system. FPGA configuration and diagnostics is controlled via low speed USB based interface, while high-speed setup of the readout parameters and reception of the measured data is handled by the PCI Express (PCIe) interface. Hardware access is synchronized by the dedicated server written in C. Multiple clients may connect to this server via TCP/IP network, and different priority is assigned to individual clients. Specialized protocols have been implemented both for low level access on register level and for high level access with transfer of structured data with "msgpack" protocol. High level functionalities have been split between multiple TCP/IP servers for parallel operation. Status of the system may be checked, and basic maintenance may be performed via web interface, while the expert access is possible via SSH server. System was designed with reliability and flexibility in mind.

  16. Modulation of Active Site Electronic Structure by the Protein Matrix to Control [NiFe] Hydrogenase Reactivity

    SciTech Connect

    Smith, Dayle MA; Raugei, Simone; Squier, Thomas C.

    2014-09-30

    Control of the reactivity of the nickel center of the [NiFe] hydrogenase and other metalloproteins commonly involves outer coordination sphere ligands that act to modify the geometry and physical properties of the active site metal centers. We carried out a combined set of classical molecular dynamics and quantum/classical mechanics calculations to provide quantitative estimates of how dynamic fluctuations of the active site within the protein matrix modulate the electronic structure at the catalytic center. Specifically we focused on the dynamics of the inner and outer coordination spheres of the cysteinate-bound Ni–Fe cluster in the catalytically active Ni-C state. There are correlated movements of the cysteinate ligands and the surrounding hydrogen-bonding network, which modulate the electron affinity at the active site and the proton affinity of a terminal cysteinate. On the basis of these findings, we hypothesize a coupling between protein dynamics and electron and proton transfer reactions critical to dihydrogen production.

  17. Test of a LYSO calorimeter prototype readout by large-area Silicon PhotoMultipliers

    NASA Astrophysics Data System (ADS)

    Guffanti, D.; Berra, A.; Lietti, D.; Prest, M.; Bonvicini, V.; Vallazza, E.; Cecchi, C.; Germani, S.; Lubrano, P.; Manoni, E.; Rossi, A.

    2014-06-01

    Large area Silicon PhotoMultipliers (SiPMs) are the new frontier of the development of readout systems for scintillating detectors. A SiPM consists of a matrix of parallel-connected silicon micropixels operating in limited Geiger-Muller avalanche mode, and thus working as independent photon counters with a very high gain (˜ 106). This contribution presents the performance in terms of linearity and energy resolution of an electromagnetic homogeneous calorimeter composed of 9 ˜ 18X0 LYSO crystals. The crystals were readout by 36 4 × 4 mm2 SiPMs (4 for each crystal) produced by FBK-irst. This calorimeter has been tested at the Beam Test Facility at the INFN laboratories in Frascati with a single- and multi-particle electron beam in the 100-500 MeV energy range.

  18. Vascular smooth muscle cells from injured rat aortas display elevated matrix production associated with transforming growth factor-beta activity.

    PubMed Central

    Rasmussen, L. M.; Wolf, Y. G.; Ruoslahti, E.

    1995-01-01

    The arterial response to injury is characterized by a short period of increased proliferation and migration of vascular smooth muscle cells, followed by an extended period of extracellular matrix accumulation in the intima. Transforming growth factor-beta (TGF-beta) has been implicated as a causative factor in the formation of extracellular matrix in this process, which leads to progressive thickening of the intima, known as intimal hyperplasia. In vitro analysis of vascular smooth muscle cells harvested from normal rat aortas and from aortas injured 14 days earlier showed that both types of cells attached equally well to culture dishes but that the initial spreading of the cells was increased in cells derived from injured vessels. Cells from the injured arteries produced more fibronectin and proteoglycans into the culture medium than the cells from normal arteries and contained more TGF-beta 1 mRNA. TGF-beta 1 increased proteoglycan synthesis by normal smooth muscle cells, and the presence of a neutralizing anti-TGF-beta 1 antibody reduced proteoglycan synthesis by the cells from injured arteries in culture. Fibronectin synthesis was not altered by these treatments. These results indicate that the accumulation of extracellular matrix components in neointimal lesions is at least partially caused by autocrine TGF-beta activity in vascular smooth muscle cells. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:7573349

  19. MicroRNA-375 Suppresses Extracellular Matrix Degradation and Invadopodial Activity in Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Jimenez, Lizandra; Sharma, Ved P.; Condeelis, John; Harris, Thomas; Ow, Thomas J.; Prystowsky, Michael B.; Childs, Geoffrey; Segall, Jeffrey E.

    2015-01-01

    Context Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer with an association with locoregional recurrence and lymph node metastasis. We have previously reported that low microRNA-375 (miR-375) expression levels correlate with poor patient survival, increased locoregional recurrence, and distant metastasis. Increasing miR-375 expression in HNSCC cell lines to levels found in normal cells results in suppressed invasive properties. HNSCC invasion is mediated in part by invadopodia-associated degradation of the extracellular matrix. Objective To determine whether elevated miR-375 expression in HNSCC cell lines also affects invadopodia formation and activity. Design For evaluation of the matrix degradation properties of the HNSCC lines, an invadopodial matrix degradation assay was used. The total protein levels of invadopodia-associated proteins were measured by Western blot analyses. Immunoprecipitation experiments were conducted to evaluate the tyrosine phosphorylation state of cortactin. Human Protease Arrays were used for the detection of the secreted proteases. Quantitative real time–polymerase chain reaction measurements were used to evaluate the messenger RNA (mRNA) expression of the commonly regulated proteases. Results Increased miR-375 expression in HNSCC cells suppresses extracellular matrix degradation and reduces the number of mature invadopodia. Higher miR-375 expression does not reduce cellular levels of selected invadopodia-associated proteins, nor is tyrosine phosphorylation of cortactin altered. However, HNSCC cells with higher miR-375 expression had significant reductions in the mRNA expression levels and secreted levels of specific proteases. Conclusions MicroRNA-375 regulates invadopodia maturation and function potentially by suppressing the expression and secretion of proteases. PMID:26172508

  20. The extracellular matrix proteins laminin and fibronectin contain binding domains for human plasminogen and tissue plasminogen activator.

    PubMed

    Moser, T L; Enghild, J J; Pizzo, S V; Stack, M S

    1993-09-01

    This study describes the binding of plasminogen and tissue-type plasminogen activator (t-PA) to the extracellular matrix proteins fibronectin and laminin. Plasminogen bound specifically and saturably to both fibronectin and laminin immobilized on microtiter wells, with Kd(app) values of 115 and 18 nM, respectively. Limited proteolysis by endoproteinase V8 coupled with ligand blotting analysis showed that both plasminogen and t-PA preferentially bind to a 55-kDa fibronectin fragment and a 38-kDa laminin fragment. Amino acid sequence analysis demonstrated that the 5-kDa fragment originates with the fibronectin amino terminus whereas the laminin fragment was derived from the carboxyl-terminal globular domain of the laminin A chain. Ligand blotting experiments using isolated plasminogen domains were also used to identify distinct regions of the plasminogen molecule involved in fibronectin and laminin binding. Solution phase fibronectin binding to immobilized plasminogen was mediated primarily via lysine binding site-dependent interactions with plasminogen kringles 1-4. Lysine binding site-dependent binding of soluble laminin to immobilized plasminogen kringles 1-5 as well as an additional lysine binding site-independent interaction between mini-plasminogen and the 38-kDa laminin A chain fragment were also observed. These studies demonstrate binding of plasminogen and tissue-type plasminogen activator to specific regions of the extracellular matrix glycoproteins laminin and fibronectin and provide further insight into the mechanism of regulation of plasminogen activation by components of the extracellular matrix. PMID:8360181

  1. Solution-Processed Organic Thin-Film Transistor Array for Active-Matrix Organic Light-Emitting Diode

    NASA Astrophysics Data System (ADS)

    Harada, Chihiro; Hata, Takuya; Chuman, Takashi; Ishizuka, Shinichi; Yoshizawa, Atsushi

    2013-05-01

    We developed a 3-in. organic thin-film transistor (OTFT) array with an ink-jetted organic semiconductor. All layers except electrodes were fabricated by solution processes. The OTFT performed well without hysteresis, and the field-effect mobility in the saturation region was 0.45 cm2 V-1 s-1, the threshold voltage was 3.3 V, and the on/off current ratio was more than 106. We demonstrated a 3-in. active-matrix organic light-emitting diode (AMOLED) display driven by the OTFT array. The display could provide clear moving images. The peak luminance of the display was 170 cd/m2.

  2. Enhanced Pixel-Driving Circuits for Active-Matrix Organic-Light-Emitting Diode Displays with Large Sizes

    NASA Astrophysics Data System (ADS)

    Yu, Sang Ho; Choi, Sung Wook; Shin, Hong Jae; Kwack, Kae Dal; Kim, Tae Whan

    2005-03-01

    Enhanced pixel-driving circuits for active-matrix organic-light-emitting diode (AM-OLED) displays with large sizes and highly uniform brightnesses were designed for system on panel. The driving method used the pre-charge functions of the data for a highly uniform brightness during a short time to program the current. The currents of the designed pixel-driving circuits were not significantly affected by variations in the threshold voltages, or by the mobilities of the driving thin-film transistors. These results indicate that the proposed pixel-driving circuits hold promise for potential applications in AM-OLED displays with large sizes and highly uniform brightnesses.

  3. Low Power, Red, Green and Blue Carbon Nanotube Enabled Vertical Organic Light Emitting Transistors for Active Matrix OLED Displays

    SciTech Connect

    McCarthy, M. A.; Liu, B.; Donoghue, E. P.; Kravchenko, Ivan I; Kim, D. Y.; So, Franky; Rinzler, A. G.

    2011-01-01

    Organic semiconductors are potential alternatives to polycrystalline silicon as the semiconductor used in the backplane of active matrix organic light emitting diode displays. Demonstrated here is a light-emitting transistor with an organic channel, operating with low power dissipation at low voltage, and high aperture ratio, in three colors: red, green and blue. The single-wall carbon nanotube network source electrode is responsible for the high level of performance demonstrated. A major benefit enabled by this architecture is the integration of the drive transistor, storage capacitor and light emitter into a single device. Performance comparable to commercialized polycrystalline-silicon TFT driven OLEDs is demonstrated.

  4. Ras activation mediates WISP-1-induced increases in cell motility and matrix metalloproteinase expression in human osteosarcoma.

    PubMed

    Wu, Chien-Lin; Tsai, Hsiao-Chi; Chen, Zhen-Wei; Wu, Chi-Ming; Li, Te-Mao; Fong, Yi-Chin; Tang, Chih-Hsin

    2013-12-01

    WISP-1 is a cysteine-rich protein that belongs to the CCN (Cyr61, CTGF, Nov) family of matrix cellular proteins. Osteosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. However, the effect of WISP-1 on migration activity in human osteosarcoma cells is mostly unknown. In this study, we first found that the expression of WISP-1 in osteosarcoma patients was significantly higher than that in normal bone and corrected with tumor stage. Exogenous treatment of osteosarcoma cells with WISP-1 promoted cell motility and matrix metalloproteinase (MMP)-2 and MMP-9 expression. In addition, the Ras and Raf-1 inhibitor or siRNA abolished WISP-1-induced cell migration and MMP expression. On the other hand, activation of the Ras, Raf-1, MEK, ERK, and NF-κB signaling pathway after WISP-1 treatment was demonstrated, and WISP-1-induced expression of MMPs and migration activity were inhibited by the specific inhibitor, and mutant of MEK, ERK, and NF-κB cascades. Taken together, our results indicated that WISP-1 enhances the migration of osteosarcoma cells by increasing MMP-2 and MMP-9 expression through the integrin receptor, Ras, Raf-1, MEK, ERK, and NF-κB signal transduction pathway.

  5. Broccoli and watercress suppress matrix metalloproteinase-9 activity and invasiveness of human MDA-MB-231 breast cancer cells.

    PubMed

    Rose, Peter; Huang, Qing; Ong, Choon Nam; Whiteman, Matt

    2005-12-01

    A high dietary intake of cruciferous vegetables has been associated with a reduction in numerous human pathologies particularly cancer. In the current study, we examined the inhibitory effects of broccoli (Brassica oleracea var. italica) and watercress (Rorripa nasturtium aquaticum) extracts on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cancer cell invasion and matrix metalloproteinase-9 activity using human MDA-MB-231 breast cancer cells. Aberrant overexpression of matrix metalloproteinases, including metalloproteinase-9, is associated with increased invasive potential in cancer cell lines. Our results demonstrate that extracts of broccoli and Rorripa suppressed TPA-induced MMP-9 activity and invasiveness in a concentration dependent manner as determined by zymographic analysis. Furthermore, fractionation of individual extracts followed by liquid chromatography mass spectroscopy analysis (LC-MS) revealed that the inhibitory effects of each vegetable were associated with the presence of 4-methysulfinylbutyl (sulforaphane) and 7-methylsulphinylheptyl isothiocyanates. Taken together, our data indicate that isothiocyanates derived form broccoli and Rorripa inhibit metalloproteinase 9 activities and also suppress the invasive potential of human MDA-MB-231 breast cancer cells in vitro. The inhibitory effects observed in the current study may contribute to the suppression of carcinogenesis by diets high in cruciferous vegetables.

  6. Broccoli and watercress suppress matrix metalloproteinase-9 activity and invasiveness of human MDA-MB-231 breast cancer cells

    SciTech Connect

    Rose, Peter . E-mail: bchpcr@nus.edu.sg; Huang, Qing; Ong, Choon Nam; Whiteman, Matt

    2005-12-01

    A high dietary intake of cruciferous vegetables has been associated with a reduction in numerous human pathologies particularly cancer. In the current study, we examined the inhibitory effects of broccoli (Brassica oleracea var. italica) and watercress (Rorripa nasturtium aquaticum) extracts on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cancer cell invasion and matrix metalloproteinase-9 activity using human MDA-MB-231 breast cancer cells. Aberrant overexpression of matrix metalloproteinases, including metalloproteinase-9, is associated with increased invasive potential in cancer cell lines. Our results demonstrate that extracts of broccoli and Rorripa suppressed TPA-induced MMP-9 activity and invasiveness in a concentration dependant manner as determined by zymographic analysis. Furthermore, fractionation of individual extracts followed by liquid chromatography mass spectroscopy analysis (LC-MS) revealed that the inhibitory effects of each vegetable were associated with the presence of 4-methysulfinylbutyl (sulforaphane) and 7-methylsulphinylheptyl isothiocyanates. Taken together, our data indicate that isothiocyanates derived form broccoli and Rorripa inhibit metalloproteinase 9 activities and also suppress the invasive potential of human MDA-MB-231 breast cancer cells in vitro. The inhibitory effects observed in the current study may contribute to the suppression of carcinogenesis by diets high in cruciferous vegetables.

  7. The Matrix Metalloproteinase Gene GmMMP2 Is Activated in Response to Pathogenic Infections in Soybean1

    PubMed Central

    Liu, Yongqing; Dammann, Christian; Bhattacharyya, Madan K.

    2001-01-01

    Matrix metalloproteinases (MMPs) play an important role in host defense responses against pathogens in mammals where their activities lead to the production of antimicrobial peptides. We have identified a novel soybean (Glycine max) metalloproteinase gene, GmMMP2, that is transcriptionally up-regulated in infected tissues. The deduced amino acid sequence indicates that this gene belongs to the MMP family. It is a preproprotein containing an N-terminal signal peptide, a cysteine switch, a zinc-binding catalytic motif, and a C-terminal transmembrane domain. The GmMMP2 expressed in and purified from Escherichia coli exhibited an in vitro enzymatic activity in digesting myelin basic protein. All plant metalloproteinases reported so far have no known functions. However, they have been suggested to be involved in extracellular cell matrix degradation during development or senescence. Our investigations demonstrate that the GmMMP2 transcript levels were rapidly increased in compatible and incompatible interactions of soybean tissues with the oomycete pathogen Phytophthora sojae or the bacterial pathogen Pseudomonas syringae pv. glycinea. In agreement with the GmMMP2 activation, a metalloproteinase activity was gradually increased in suspension-cultured cells following the bacterial infection. GmMMP2 was also activated in response to wounding and dehydration. However, GmMMP2 activation did not correlate with the oxidative burst leading to the hypersensitive response cell death or the tissue senescence progress that involves programmed cell death. Our investigations suggest that GmMMP2 may be involved in a novel defense response of soybean against pathogenic infections. PMID:11743122

  8. Activation of matrix metalloproteinase-26 by HOXA10 promotes embryo adhesion in vitro.

    PubMed

    Jiang, Yue; Yan, Guijun; Zhang, Hui; Shan, Huizhi; Kong, Chengcai; Yan, Qiang; Xue, Bai; Diao, Zhenyu; Hu, Yali; Sun, Haixiang

    2014-03-14

    Successful embryonic implantation requires an effective maternal-embryonic molecular dialogue. However, the detailed mechanisms of epithelial-embryo adhesion remain poorly understood. Here, we report that matrix metalloproteinase-26 (MMP-26) is a novel downstream target gene of homeobox a 10 (HOXA10) in human endometrial cells. HOXA10 binds directly to a conserved TTAT unit (-442 to -439) located within the 5' regulatory region of the MMP-26 gene and regulates the expression and secretion of MMP-26 in a concentration-dependent manner. Moreover, the adenovirus-mediated overexpression of MMP-26 in Ishikawa cells markedly increased BeWo spheroid adhesion. An antibody blocking assay further demonstrated that the promotion of BeWo spheroid adhesion by HOXA10 and MMP-26 was significantly inhibited by pre-treatment with a specific antibody against MMP-26. These results demonstrate that the HOXA10-mediated expression of MMP-26 promotes embryo adhesion during the process of embryonic implantation. PMID:24565841

  9. Active mechanical coupling between the nucleus, cytoskeleton and the extracellular matrix, and the implications for perinuclear actomyosin organization.

    PubMed

    Zemel, Assaf

    2015-03-28

    Experimental and theoretical studies have demonstrated that the polarization of actomyosin forces in the cytoskeleton of adherent cells is governed by local elastic stresses. Based on this phenomenon, and the established observation that the nucleus is mechanically connected to the extracellular matrix (ECM) via the cytoskeleton, we theoretically analyze here the active mechanical coupling between the nucleus, cytoskeleton and the ECM. The cell is modeled as an active spherical inclusion, containing a round nucleus at its center, and embedded in a 3D elastic matrix. We investigate three sources of cellular stress: spreading-induced stress, actomyosin contractility and chromatin entropic forces. Formulating the coupling of actomyosin contractility to the local stress we predict the consequences that the nucleus, cytoskeleton and ECM mechanical properties may have on the overall force-balance in the cell and the perinuclear acto-myosin polarization. We demonstrate that the presence of the nucleus induces symmetry breaking of the elastic stress that, we predict, elastically tends to orient actomyosin alignment tangentially around the nucleus; the softer the nucleus or the matrix, the stronger is the preference for tangential alignment. Spreading induced stresses may induce radial actomyosin alignment near stiff nuclei. In addition, we show that in regions of high actomyosin density myosin motors have an elastic tendency to orient tangentially as often occurs near the cell periphery. These conclusions highlight the role of the nucleus in the regulation of cytoskeleton organization and may provide new insight into the mechanics of stem cell differentiation involving few fold increase in nucleus stiffness. PMID:25652010

  10. Data encoding efficiency in pixel detector readout with charge information

    NASA Astrophysics Data System (ADS)

    Garcia-Sciveres, Maurice; Wang, Xinkang

    2016-04-01

    The average minimum number of bits needed for lossless readout of a pixel detector is calculated, in the regime of interest for particle physics where only a small fraction of pixels have a non-zero value per frame. This permits a systematic comparison of the readout efficiency of different encoding implementations. The calculation is compared to the number of bits used by the FE-I4 pixel readout chip of the ATLAS experiment.

  11. Pixel readout electronics for LHC and biomedical applications

    NASA Astrophysics Data System (ADS)

    Blanquart, L.; Bonzom, V.; Comes, G.; Delpierre, P.; Fischer, P.; Hausmann, J.; Keil, M.; Lindner, M.; Meuser, S.; Wermes, N.

    2000-01-01

    The demanding requirements for pixel readout electronics for high-energy physics experiments and biomedical applications are reviewed. Some examples of the measured analog performance of prototype chips are given. The readout architectures of the PIxel Readout for the ATlas Experiment (PIRATE) chip suited for LHC experiments and of the Multi Picture Element Counter (MPEC) counting chip targeted for biomedical applications are presented. First results with complete chip-sensor assemblies are also shown.

  12. Factor H-related protein 5 interacts with pentraxin 3 and the extracellular matrix and modulates complement activation.

    PubMed

    Csincsi, Ádám I; Kopp, Anne; Zöldi, Miklós; Bánlaki, Zsófia; Uzonyi, Barbara; Hebecker, Mario; Caesar, Joseph J E; Pickering, Matthew C; Daigo, Kenji; Hamakubo, Takao; Lea, Susan M; Goicoechea de Jorge, Elena; Józsi, Mihály

    2015-05-15

    The physiological roles of the factor H (FH)-related proteins are controversial and poorly understood. Based on genetic studies, FH-related protein 5 (CFHR5) is implicated in glomerular diseases, such as atypical hemolytic uremic syndrome, dense deposit disease, and CFHR5 nephropathy. CFHR5 was also identified in glomerular immune deposits at the protein level. For CFHR5, weak complement regulatory activity and competition for C3b binding with the plasma complement inhibitor FH have been reported, but its function remains elusive. In this study, we identify pentraxin 3 (PTX3) as a novel ligand of CFHR5. Binding of native CFHR5 to PTX3 was detected in human plasma and the interaction was characterized using recombinant proteins. The binding of PTX3 to CFHR5 is of ∼2-fold higher affinity compared with that of FH. CFHR5 dose-dependently inhibited FH binding to PTX3 and also to the monomeric, denatured form of the short pentraxin C-reactive protein. Binding of PTX3 to CFHR5 resulted in increased C1q binding. Additionally, CFHR5 bound to extracellular matrix in vitro in a dose-dependent manner and competed with FH for binding. Altogether, CFHR5 reduced FH binding and its cofactor activity on pentraxins and the extracellular matrix, while at the same time allowed for enhanced C1q binding. Furthermore, CFHR5 allowed formation of the alternative pathway C3 convertase and supported complement activation. Thus, CFHR5 may locally enhance complement activation via interference with the complement-inhibiting function of FH, by enhancement of C1q binding, and by activating complement, thereby contributing to glomerular disease.

  13. A program of cell death and extracellular matrix degradation is activated in the amnion before the onset of labor.

    PubMed Central

    Lei, H; Furth, E E; Kalluri, R; Chiou, T; Tilly, K I; Tilly, J L; Elkon, K B; Jeffrey, J J; Strauss, J F

    1996-01-01

    Fetal membranes usually rupture during the process of labor. Premature fetal membrane rupture occurs not infrequently and is associated with significant fetal and maternal morbidity. The mechanisms of normal and pathologic fetal membrane rupture are not well understood. We have examined structural and biochemical changes in the rat amnion as labor approaches in order to characterize this process in normal pregnancy. Here we report that before the onset of active labor the amnion epithelial cells undergo apoptotic cell death which encompasses degradation of 28S ribosomal subunit RNA and associated P proteins and fragmentation of nuclear DNA. Concurrent with these cellular changes, the amnion type I collagen matrix is degraded with the accumulation of three-quarter length type I collagen fragments in extraembryonic fluid, characteristic of the cleavage of fibrillar collagen by interstitial collagenase. Western blot and immunohistochemical analyses confirmed that interstitial collagenase protein appears in association with the loss of amnion type I collagen. We conclude that amnion epithelial cells undergo a process of programmed cell death associated with orchestrated extracellular matrix degradation which begins before the onset of active labor. Thus, fetal membrane rupture is likely to be the result of biochemical changes as well as physical forces. PMID:8903315

  14. Approach to In- Situ Producing Reinforcing Phase Within an Active-Transient Liquid Phase Bond Seam for Aluminum Matrix Composite

    NASA Astrophysics Data System (ADS)

    Zhang, Guifeng; Liao, Xianjin; Chen, Bo; Zhang, Linjie; Zhang, Jianxun

    2015-06-01

    To optimize the braze composition design route for aluminum matrix composite, the feasibility of in situ producing reinforcing phase within the transient liquid phase bond seam matrix, by adding active melting point increaser (MPI, e.g., Ti) together with general melting point depressant (MPD, e.g., Cu) into the interlayer, was demonstrated. For SiC p /A356 composite, by comparing the wettability, joint microstructure, joint shear strength, and fracture path for the developed Al-19Cu-1Ti, Al-19Cu, Al-33Cu-1Ti, Al-33Cu (wt pct), and commercial Cu foils as interlayer, the feasibility of in situ producing reinforcing phase within the bond seam by adding Ti was demonstrated. Especially for Al-19Cu-1Ti active braze, small and dispersed ternary aluminide of Al-Si-Ti phase was obtained within the bond seam as in situ reinforcement, leading to a favorable fracture path within SiC p /A356, not along the initial interface or within the bond seam. For the formation mechanism of the in situ reinforcing phase of MPI-containing intermetallic compound within the bond seam, a model of repeating concentration-precipitation-termination-engulfment during isothermal solidification is proposed.

  15. Characterization of Xenopus Tissue Inhibitor of Metalloproteinases-2: A Role in Regulating Matrix Metalloproteinase Activity during Development

    PubMed Central

    Fiorentino, Maria; Shi, Yun-Bo

    2012-01-01

    Background Frog metamorphosis is totally dependent on thyroid hormone (T3) and mimics the postembryonic period around birth in mammals. It is an excellent model to study the molecular basis of postembryonic development in vertebrate. We and others have shown that many, if not all, matrix metalloproteinases (MMPs), which cleave proteins of the extracellular matrix as well as other substrates, are induced by T3 and important for metamorphosis. MMP activity can be inhibited by tissue inhibitors of metalloproteinase (TIMPs). There are 4 TIMPs in vertebrates and their roles in postembryonic development are poorly studied. Methodology/Principal Findings We analyzed the TIMP2 genes in Xenopus laevis and the highly related species Xenopus tropicalis and discovered that TIMP2 is a single copy gene in Xenopus tropicalis as in mammals but is duplicated in Xenopus laevis. Furthermore, the TIMP2 locus in Xenopus tropicalis genome is different from that in human, suggesting an evolutionary reorganization of the locus. More importantly, we found that the duplicated TIMP2 genes were similarly regulated in the developing limb, remodeling intestine, resorbing tail during metamorphosis. Unexpectedly, like its MMP target genes, the TIMP2 genes were upregulated by T3 during both natural and T3-induced metamorphosis. Conclusions/Significance Our results indicate that TIMP2 is highly conserved among vertebrates and that the TIMP2 locus underwent a chromosomal reorganization during evolution. Furthermore, the unexpected upregulation of TIMP2 genes during metamorphosis suggests that proper balance of MMP activity is important for metamorphosis. PMID:22693555

  16. A Readout Mechanism for Latency Codes

    PubMed Central

    Zohar, Oran; Shamir, Maoz

    2016-01-01

    Response latency has been suggested as a possible source of information in the central nervous system when fast decisions are required. The accuracy of latency codes was studied in the past using a simplified readout algorithm termed the temporal-winner-take-all (tWTA). The tWTA is a competitive readout algorithm in which populations of neurons with a similar decision preference compete, and the algorithm selects according to the preference of the population that reaches the decision threshold first. It has been shown that this algorithm can account for accurate decisions among a small number of alternatives during short biologically relevant time periods. However, one of the major points of criticism of latency codes has been that it is unclear how can such a readout be implemented by the central nervous system. Here we show that the solution to this long standing puzzle may be rather simple. We suggest a mechanism that is based on reciprocal inhibition architecture, similar to that of the conventional winner-take-all, and show that under a wide range of parameters this mechanism is sufficient to implement the tWTA algorithm. This is done by first analyzing a rate toy model, and demonstrating its ability to discriminate short latency differences between its inputs. We then study the sensitivity of this mechanism to fine-tuning of its initial conditions, and show that it is robust to wide range of noise levels in the initial conditions. These results are then generalized to a Hodgkin-Huxley type of neuron model, using numerical simulations. Latency codes have been criticized for requiring a reliable stimulus-onset detection mechanism as a reference for measuring latency. Here we show that this frequent assumption does not hold, and that, an additional onset estimator is not needed to trigger this simple tWTA mechanism. PMID:27812332

  17. Tumor necrosis factor-alpha induced expression of matrix metalloproteinase-9 through p21-activated Kinase-1

    PubMed Central

    Zhou, Ling; Yan, Chunli; Gieling, Roben G; Kida, Yujiro; Garner, Warren; Li, Wei; Han, Yuan-Ping

    2009-01-01

    Background Expressed in embryonic development, matrix metalloprotein-9 (MMP-9) is absent in most of developed adult tissues, but recurs in inflammation during tissue injury, wound healing, tumor formation and metastasis. Expression of MMP-9 is tightly controlled by extracellular cues including pro-inflammatory cytokines and extracellular matrix (ECM). While the pathologic functions of MMP-9 are evident, the intracellular signaling pathways to control its expression are not fully understood. In this study we investigated mechanism of cytokine induced MMP-9 with particular emphasis on the role of p21-activated-kinase-1 (PAK1) and the down stream signaling. Results In response to TNF-alpha or IL-1alpha, PAK1 was promptly activated, as characterized by a sequential phosphorylation, initiated at threonine-212 followed by at threonine-423 in the activation loop of the kinase, in human skin keratinocytes, dermal fibroblasts, and rat hepatic stellate cells. Ectopic expression of PAK1 variants, but not p38 MAP kinase, impaired the TNF-alpha-induced MMP-9 expression, while other MMPs such as MMP-2, -3 and -14 were not affected. Activation of Jun N-terminal kinase (JNK) and NF-kappaB has been demonstrated to be essential for MMP-9 expression. Expression of inactive PAK1 variants impaired JNK but not NF-kappaB activation, which consequently suppressed the 5'-promoter activities of the MMP-9 gene. After the cytokine-induced phosphorylation, both ectopically expressed and endogenous PAK1 proteins were promptly accumulated even in the condition of suppressing protein synthesis, suggesting the PAK1 protein is stabilized upon TNF-alpha stimulation. Stabilization of PAK1 protein by TNF-alpha treatment is independent of the kinase catalytic activity and p21 GTPase binding capacities. In contrast to epithelial cells, mesenchymal cells require 3-dimensional type-I collagen in response to TNF-alpha to massively express MMP-9. The collagen effect is mediated, in part, by boost JNK

  18. Asynchronous data readout system for multichannel ASIC

    NASA Astrophysics Data System (ADS)

    Ivanov, P. Y.; Atkin, E. V.

    2016-02-01

    The data readout system of multichannel data-driven ASIC, requiring high-speed (320 Mb/s) output data serialization is described. Its structure, based on a limited number of FIFO blocks, provides a lossless data transfer. The solution has been realized as a separate test IP block in the prototyped 8 channel ASIC, intended for the muon chamber of CBM experiment at FAIR. The block was developed for the UMC 0.18 μm MMRF CMOS process and prototyped via Europractice. Main parameters of the chip are given.

  19. Influenza matrix protein 2 alters CFTR expression and function through its ion channel activity.

    PubMed

    Londino, James D; Lazrak, Ahmed; Jurkuvenaite, Asta; Collawn, James F; Noah, James W; Matalon, Sadis

    2013-05-01

    The human cystic fibrosis transmembrane conductance regulator (CFTR) is a cyclic AMP-activated chloride (Cl(-)) channel in the lung epithelium that helps regulate the thickness and composition of the lung epithelial lining fluid. We investigated whether influenza M2 protein, a pH-activated proton (H(+)) channel that traffics to the plasma membrane of infected cells, altered CFTR expression and function. M2 decreased CFTR activity in 1) Xenopus oocytes injected with human CFTR, 2) epithelial cells (HEK-293) stably transfected with CFTR, and 3) human bronchial epithelial cells (16HBE14o-) expressing native CFTR. This inhibition was partially reversed by an inhibitor of the ubiquitin-activating enzyme E1. Next we investigated whether the M2 inhibition of CFTR activity was due to an increase of secretory organelle pH by M2. Incubation of Xenopus oocytes expressing CFTR with ammonium chloride or concanamycin A, two agents that alkalinize the secretory pathway, inhibited CFTR activity in a dose-dependent manner. Treatment of M2- and CFTR-expressing oocytes with the M2 ion channel inhibitor amantadine prevented the loss in CFTR expression and activity; in addition, M2 mutants, lacking the ability to transport H(+), did not alter CFTR activity in Xenopus oocytes and HEK cells. Expression of an M2 mutant retained in the endoplasmic reticulum also failed to alter CFTR activity. In summary, our data show that M2 decreases CFTR activity by increasing secretory organelle pH, which targets CFTR for destruction by the ubiquitin system. Alteration of CFTR activity has important consequences for fluid regulation and may potentially modify the immune response to viral infection.

  20. Influenza matrix protein 2 alters CFTR expression and function through its ion channel activity

    PubMed Central

    Londino, James D.; Lazrak, Ahmed; Jurkuvenaite, Asta; Collawn, James F.; Noah, James W.

    2013-01-01

    The human cystic fibrosis transmembrane conductance regulator (CFTR) is a cyclic AMP-activated chloride (Cl−) channel in the lung epithelium that helps regulate the thickness and composition of the lung epithelial lining fluid. We investigated whether influenza M2 protein, a pH-activated proton (H+) channel that traffics to the plasma membrane of infected cells, altered CFTR expression and function. M2 decreased CFTR activity in 1) Xenopus oocytes injected with human CFTR, 2) epithelial cells (HEK-293) stably transfected with CFTR, and 3) human bronchial epithelial cells (16HBE14o−) expressing native CFTR. This inhibition was partially reversed by an inhibitor of the ubiquitin-activating enzyme E1. Next we investigated whether the M2 inhibition of CFTR activity was due to an increase of secretory organelle pH by M2. Incubation of Xenopus oocytes expressing CFTR with ammonium chloride or concanamycin A, two agents that alkalinize the secretory pathway, inhibited CFTR activity in a dose-dependent manner. Treatment of M2- and CFTR-expressing oocytes with the M2 ion channel inhibitor amantadine prevented the loss in CFTR expression and activity; in addition, M2 mutants, lacking the ability to transport H+, did not alter CFTR activity in Xenopus oocytes and HEK cells. Expression of an M2 mutant retained in the endoplasmic reticulum also failed to alter CFTR activity. In summary, our data show that M2 decreases CFTR activity by increasing secretory organelle pH, which targets CFTR for destruction by the ubiquitin system. Alteration of CFTR activity has important consequences for fluid regulation and may potentially modify the immune response to viral infection. PMID:23457187

  1. Activation of toll-like receptor-2 by endogenous matrix metalloproteinase-2 modulates dendritic-cell-mediated inflammatory responses.

    PubMed

    Godefroy, Emmanuelle; Gallois, Anne; Idoyaga, Juliana; Merad, Miriam; Tung, Navpreet; Monu, Ngozi; Saenger, Yvonne; Fu, Yichun; Ravindran, Rajesh; Pulendran, Bali; Jotereau, Francine; Trombetta, Sergio; Bhardwaj, Nina

    2014-12-11

    Matrix metalloproteinase-2 (MMP-2) is involved in several physiological mechanisms, including wound healing and tumor progression. We show that MMP-2 directly stimulates dendritic cells (DCs) to both upregulate OX40L on the cell surface and secrete inflammatory cytokines. The mechanism underlying DC activation includes physical association with Toll-like receptor-2 (TLR2), leading to NF-κB activation, OX40L upregulation on DCs, and ensuing TH2 differentiation. Significantly, MMP-2 polarizes T cells toward type 2 responses in vivo, in a TLR2-dependent manner. MMP-2-dependent type 2 polarization may represent a key immune regulatory mechanism for protection against a broad array of disorders, such as inflammatory, infectious, and autoimmune diseases, which can be hijacked by tumors to evade immunity.

  2. Activation of Toll-like receptor-2 by endogenous matrix metalloproteinase-2 modulates dendritic cell-mediated inflammatory responses

    PubMed Central

    Godefroy, Emmanuelle; Gallois, Anne; Idoyaga, Juliana; Merad, Miriam; Tung, Navpreet; Monu, Ngozi; Saenger, Yvonne; Fu, Yichun; Nair, Rajesh; Pulendran, Bali; Jotereau, Francine; Trombetta, Sergio; Bhardwaj, Nina

    2015-01-01

    SUMMARY Matrix metalloproteinase-2 (MMP-2) is involved in several physiological mechanisms, including wound healing and tumor progression. We show that MMP-2 directly stimulates dendritic cells (DCs) to both up-regulate OX40L on the cell surface and secrete inflammatory cytokines. The mechanism underlying DC activation includes physical association with Toll-like receptor-2 (TLR2), leading to NF-κB activation, OX40L up-regulation on DCs and ensuing TH2 differentiation. Significantly, MMP-2 polarizes T cells towards type-2 responses in vivo, in a TLR2-dependent manner. MMP-2-dependent type-2 polarization may represent a key immune regulatory mechanism to protect against a broad array of disorders, such as inflammatory, infectious and autoimmune diseases, which can be hijacked by tumors to evade immunity. PMID:25466255

  3. Ratio of Active Matrix Metalloproteinases and Proenzymes during Growth and Metastasizing of Mouse Lewis Lung Adenocarcinoma.

    PubMed

    Kisarova, Ya A; Kaledin, V I; Bogdanova, L A; Korolenko, T A

    2015-08-01

    Ratio between proMMP and active MMP was studied in the dynamics of growth of the Lewis lung adenocarcinoma with lung metastasis. It was shown that tumor growth is associated with an increase in the content of proMMP (day 20; terminal stage), but the level of active MMP in tumor tissue did not signifi cantly change. The development of lung metastasis was accompanied by accumulation of active MMP (days 7, 15, and 20) and a decrease in the content of pro-MMP (days 7, and 20) in comparison with the control. In the spleen of these mice (metastasis-free organ), an increase in the levels of proMMP (day 20) and especially active MMP (days 7, 15, and 20) were found. The results suggest that tumor development shifts the proportion between active MMP and proenzymes in the tumor, lungs with metastasis, and spleen without metastasis. PMID:26392281

  4. Ratio of Active Matrix Metalloproteinases and Proenzymes during Growth and Metastasizing of Mouse Lewis Lung Adenocarcinoma.

    PubMed

    Kisarova, Ya A; Kaledin, V I; Bogdanova, L A; Korolenko, T A

    2015-08-01

    Ratio between proMMP and active MMP was studied in the dynamics of growth of the Lewis lung adenocarcinoma with lung metastasis. It was shown that tumor growth is associated with an increase in the content of proMMP (day 20; terminal stage), but the level of active MMP in tumor tissue did not signifi cantly change. The development of lung metastasis was accompanied by accumulation of active MMP (days 7, 15, and 20) and a decrease in the content of pro-MMP (days 7, and 20) in comparison with the control. In the spleen of these mice (metastasis-free organ), an increase in the levels of proMMP (day 20) and especially active MMP (days 7, 15, and 20) were found. The results suggest that tumor development shifts the proportion between active MMP and proenzymes in the tumor, lungs with metastasis, and spleen without metastasis.

  5. Evolution of a supercooled Ice Shelf Water plume with an actively growing subice platelet matrix

    NASA Astrophysics Data System (ADS)

    Robinson, Natalie J.; Williams, Michael J. M.; Stevens, Craig L.; Langhorne, Patricia J.; Haskell, Timothy G.

    2014-06-01

    We use new observations in Western McMurdo Sound, combined with longitudinal hydrographic transects of the sound, to identify a northward-flowing Ice Shelf Water (ISW) plume exiting the cavity of the McMurdo-Ross Ice Shelf. We estimate the plume's net northward transport at 0.4 ± 0.1 Sv, carving out a corridor approximately 35 km wide aligned with the Victoria Land Coast. Basal topography of the McMurdo Ice Shelf is such that the plume is delivered to the surface without mixing with overlying warmer water, and is therefore able to remain below the surface freezing temperature at the point of observation beneath first-year ice. Thus, the upper ocean was supercooled, by up to 50 mK at the surface, due to pressure relief from recent rapid ascent of the steep basal slope. The 70 m thick supercooled layer supports the growth and maintenance of a thick, semirigid, and porous matrix of platelet ice, which is trapped by buoyancy at the ice-ocean interface. Continued growth of individual platelets in supercooled water creates significant brine rejection at the top of the water column which resulted in convection over the upper 200 m thick, homogeneous layer. By examining the diffusive nature of the intermediate water between layers of ISW and High Salinity Shelf Water, we conclude that the ISW plume must have originated beneath the Ross Ice Shelf and demonstrate that it is likely to expand eastward across McMurdo Sound with the progression of winter.

  6. Matrix Domain Modulates HIV-1 Gag's Nucleic Acid Chaperone Activity via Inositol Phosphate Binding ▿

    PubMed Central

    Jones, Christopher P.; Datta, Siddhartha A. K.; Rein, Alan; Rouzina, Ioulia; Musier-Forsyth, Karin

    2011-01-01

    Retroviruses replicate by reverse transcribing their single-stranded RNA genomes into double-stranded DNA using specific cellular tRNAs to prime cDNA synthesis. In HIV-1, human tRNA3Lys serves as the primer and is packaged into virions during assembly. The viral Gag protein is believed to chaperone tRNA3Lys placement onto the genomic RNA primer binding site; however, the timing and possible regulation of this event are currently unknown. Composed of the matrix (MA), capsid (CA), nucleocapsid (NC), and p6 domains, the multifunctional HIV-1 Gag polyprotein orchestrates the highly coordinated process of virion assembly, but the contribution of these domains to tRNA3Lys annealing is unclear. Here, we show that NC is absolutely essential for annealing and that the MA domain inhibits Gag's tRNA annealing capability. During assembly, MA specifically interacts with inositol phosphate (IP)-containing lipids in the plasma membrane (PM). Surprisingly, we find that IPs stimulate Gag-facilitated tRNA annealing but do not stimulate annealing in Gag variants lacking the MA domain or containing point mutations involved in PM binding. Moreover, we find that IPs prevent MA from binding to nucleic acids but have little effect on NC or Gag. We propose that Gag binds to RNA either with both NC and MA domains or with NC alone and that MA-IP interactions alter Gag's binding mode. We propose that MA's interactions with the PM trigger the switch between these two binding modes and stimulate Gag's chaperone function, which may be important for the regulation of events such as tRNA primer annealing. PMID:21123373

  7. Simultaneous parallel inclined readout image technique.

    PubMed

    Paley, Martyn N J; Lee, Kuan J; Wild, James M; Griffiths, Paul D; Whitby, Elspeth H

    2006-06-01

    Sensitivity-encoded phase undersampling has been combined with simultaneous slice excitation to produce a parallel MRI method with a high volumetric acquisition acceleration factor without the need for auxiliary stepped field coils. Dual-slice excitation was produced by modulating both spin and gradient echo sequences at +/-6 kHz. Frequency aliasing of simultaneously excited slices was prevented by using an additional gradient applied along the slice axis during data acquisition. Data were acquired using a four-channel receiver array and x4 sensitivity encoding on a 1.5 T MR system. The simultaneous parallel inclined readout image technique has been successfully demonstrated in both phantoms and volunteers. A multiplicative image acquisition acceleration factor of up to x8 was achieved. Image SNR and resolution was dependent on the ratio of the readout gradient to the additional slice gradient. A ratio of approximately 2:1 produced acceptable image quality. Use of RF pulses with additional excitation bands should enable the technique to be extended to volumetric acquisition acceleration factors in the range of x16-24 without the SNR limitations of pure partially parallel phase reduction methods.

  8. Semiconductor detectors with proximity signal readout

    SciTech Connect

    Asztalos, Stephen J.

    2014-01-30

    Semiconductor-based radiation detectors are routinely used for the detection, imaging, and spectroscopy of x-rays, gamma rays, and charged particles for applications in the areas of nuclear and medical physics, astrophysics, environmental remediation, nuclear nonproliferation, and homeland security. Detectors used for imaging and particle tracking are more complex in that they typically must also measure the location of the radiation interaction in addition to the deposited energy. In such detectors, the position measurement is often achieved by dividing or segmenting the electrodes into many strips or pixels and then reading out the signals from all of the electrode segments. Fine electrode segmentation is problematic for many of the standard semiconductor detector technologies. Clearly there is a need for a semiconductor-based radiation detector technology that can achieve fine position resolution while maintaining the excellent energy resolution intrinsic to semiconductor detectors, can be fabricated through simple processes, does not require complex electrical interconnections to the detector, and can reduce the number of required channels of readout electronics. Proximity electrode signal readout (PESR), in which the electrodes are not in physical contact with the detector surface, satisfies this need.

  9. Experimental vortex transitional nondestructive read-out Josephson memory cell

    SciTech Connect

    Tahara, S.; Ishida, I.; Ajisawa, Y.; Wada, Y.

    1989-01-15

    A proposal vortex transitional nondestructive read-out Josephson memory cell is successfully fabricated and tested. The memory cell consists of two superconducting loops in which a single flux quantum is stored and a two-junction interferometer gate as a sense gate. The memory cell employs vortex transitions in the superconducting loops for writing and reading data. The vortex transitional memory operation of the cell contributes to improving its sense discrimination and operating margin. The memory cell is activated by two control signals without timing control signals. Memory cell chips have been fabricated using a niobium planarization process. A +- 21% address signal current margin and a +- 33% sense gate current margin have been obtained experimentally. Successful memory operations of a cell driven by two-junction interferometer gates has been demonstrated. The single flux quantum operations of this memory cell makes it an attractive basic element for a high-speed cache memory.

  10. Activities of matrix metalloproteinases and tissue inhibitor of metalloproteinase-2 in idiopathic hemotympanum and otitis media with effusion

    PubMed Central

    Moon, Sung K.; Linthicum, Fred H.; Yang, Hae Dong; Lee, Seung Joo; Park, Keehyun

    2008-01-01

    Conclusion The expression profile of matrix metalloproteinases (MMP) and tissue inhibitor of metalloproteinase-2 (TIMP-2) was specific to the type of middle ear effusion. Further studies are necessary for elucidating its correlation with the sequelae of otitis media with effusion (OME) and idiopathic hemotympanum. Objectives We aimed to investigate the relative activities of gelatinases (MMP-2 and 9), stromelysin-1 (MMP-3), matrilysin-1 (MMP-7) as well as measuring TIMP-2 levels in the serous and mucous effusions of OME and hemorrhagic effusion of the idiopathic hemotympanum. Method Middle ear effusions were collected from patients with OME and idiopathic hemotympanum, and were classified as mucoid, serous or hemorrhagic. MMP activity in the effusion samples was examined by gelatin and casein zymography. Levels of TIMP-2 were measured by ELISA. Human temporal bones sections, with and without otitis media (OM), were examined histologically. Results One case showed tympanic membrane thinning in the OM group, but none in the control group. While MMP-2 was present in all effusions, the active form of MMP-2 was found only in mucous effusions. MMP-3 and MMP-7 activity was detected only in the mucous effusions. MMP-9 exhibited activity in all effusions, with the highest levels in mucous effusions. TIMP-2 levels were markedly elevated in serous effusions. PMID:17851959

  11. Growth-inhibiting extracellular matrix proteins also inhibit electrical activity by reducing calcium and increasing potassium conductances.

    PubMed

    Vargas, J; De-Miguel, F F

    2009-01-23

    Inhibitionof neurite sprouting and electrical activity by extracellular matrix (ECM) glycoproteins was studied during neurite regeneration by using anterior pagoda (AP) neurons of the leech. Adult isolated neurons were plated in culture inside ganglion capsules, which among many ECM proteins, contain a group of inhibitory peanut lectin- (PNA) binding glycoproteins. These proteins inhibit neurite production and contribute to the formation of a bipolar outgrowth pattern by AP neurons. Addition of PNA lectin to the culture medium to block the inhibitory effects of ECM glycoproteins induced an increase of neurite sprouting, the loss of the bipolar pattern, and also an increase in the amplitude and duration of action potentials evoked by intracellular current injection. PNA lectin had independent effects on neurite sprouting and electrical activity, since there was no correlation between the total neurite length and the amplitude of the action potentials. Moreover, action potentials were increased by the presence of PNA lectin even in neurons that did not grow. The changes induced by PNA lectin on the active conductances underlying the action potentials were estimated by quantitative model simulations. We predict that the increases in the amplitude and duration of the action potential induced by PNA lectin were due to an increase in a calcium conductance and a reduction in the delayed rectifier potassium conductance. Our results suggest that inhibitory ECM glycoproteins may use independent signaling pathways to inhibit neurite sprouting and electrical activity. These proteins affect the action potential by changing the proportion of inward and outward active conductances. PMID:18976697

  12. High-speed readout solution for single-photon counting ASICs

    NASA Astrophysics Data System (ADS)

    Kmon, P.; Szczygiel, R.; Maj, P.; Grybos, P.; Kleczek, R.

    2016-02-01

    We report on the analysis, simulations and measurements of both noise and high-count rate performance of a single photon counting integrated circuit called UFXC32k designed for hybrid pixel detectors for various applications in X-ray imaging. The dimensions of the UFCX32k designed in CMOS 130 nm technology are 9.63 mm × 20.15 mm. The integrated circuit core is a matrix of 128 × 256 squared readout pixels with a pitch of 75 μm. Each readout pixel contains a charge sensitive amplifier (CSA), a shaper, two discriminators and two 14-bit ripple counters. The UFXC32k was bump-bonded to a silicon pixel detector with the thickness of 320 μm and characterized with the X-ray radiation source. The CSA feedback based on the Krummenacher circuit determines both the count rate performance and the noise of the readout front-end electronics. For the default setting of the CSA feedback, the measured front-end electronics dead time is 232 ns (paralyzable model) and the equivalent noise charge (ENC) is equal to 123 el. rms. For the high count rate setting of the CSA feedback, the dead time is only 101 ns and the ENC is equal to 163 el. rms.

  13. Interfacial Engineering of Bimetallic Ag/Pt Nanoparticles on Reduced Graphene Oxide Matrix for Enhanced Antimicrobial Activity.

    PubMed

    Zhang, Mei; Zhao, Yanhua; Yan, Li; Peltier, Raoul; Hui, Wenli; Yao, Xi; Cui, Yali; Chen, Xianfeng; Sun, Hongyan; Wang, Zuankai

    2016-04-01

    Environmental biofouling caused by the formation of biofilm has been one of the most urgent global concerns. Silver nanoparticles (NPs), owing to their wide-spectrum antimicrobial property, have been widely explored to combat biofilm, but their extensive use has raised growing concern because they persist in the environment. Here we report a novel hybrid nanocomposite that imparts enhanced antimicrobial activity and low cytotoxicity yet with the advantage of reduced silver loading. The nanocomposite consists of Pt/Ag bimetallic NPs (BNPs) decorated on the porous reduced graphene oxide (rGO) nanosheets. We demonstrate that the enhanced antimicrobial property against Escherichia coli is ascribed to the intricate control of the interfaces between metal compositions, rGO matrix, and bacteria, where the BNPs lead to a rapid release of silver ions, and the trapping of bacteria by the porous rGO matrix further provides high concentration silver ion sites for efficient bacteria-bactericide interaction. We envision that our facile approach significantly expands the design space for the creation of silver-based antimicrobial materials to achieve a wide spectrum of functionalities. PMID:27007980

  14. Regulation of Matrix Metalloproteinase-2 Activity by COX-2-PGE2-pAKT Axis Promotes Angiogenesis in Endometriosis

    PubMed Central

    Ray, Amlan K.; DasMahapatra, Pramathes; Swarnakar, Snehasikta

    2016-01-01

    Endometriosis is characterized by the ectopic development of the endometrium which relies on angiogenesis. Although studies have identified the involvement of different matrix metalloproteinases (MMPs) in endometriosis, no study has yet investigated the role of MMP-2 in endometriosis-associated angiogenesis. The present study aims to understand the regulation of MMP-2 activity in endothelial cells and on angiogenesis during progression of ovarian endometriosis. Histological and biochemical data showed increased expressions of vascular endothelial growth factor (VEGF), VEGF receptor-2, cycloxygenase (COX)-2, von Willebrand factor along with angiogenesis during endometriosis progression. Women with endometriosis showed decreased MMP-2 activity in eutopic endometrium as compared to women without endometriosis. However, ectopic ovarian endometrioma showed significantly elevated MMP-2 activity with disease severity. In addition, increased MT1MMP and decreased tissue inhibitors of metalloproteinases (TIMP)-2 expressions were found in the late stages of endometriosis indicating more MMP-2 activation with disease progression. In vitro study using human endothelial cells showed that prostaglandin E2 (PGE2) significantly increased MMP-2 activity as well as tube formation. Inhibition of COX-2 and/or phosphorylated AKT suppressed MMP-2 activity and endothelial tube formation suggesting involvement of PGE2 in regulation of MMP-2 activity during angiogenesis. Moreover, specific inhibition of MMP-2 by chemical inhibitor significantly reduced cellular migration, invasion and tube formation. In ovo assay showed decreased angiogenic branching upon MMP-2 inhibition. Furthermore, a significant reduction of lesion numbers was observed upon inhibition of MMP-2 and COX-2 in mouse model of endometriosis. In conclusion, our study establishes the involvement of MMP-2 activity via COX-2-PGE2-pAKT axis in promoting angiogenesis during endometriosis progression. PMID:27695098

  15. Conformable, flexible, large-area networks of pressure and thermal sensors with organic transistor active matrixes

    NASA Astrophysics Data System (ADS)

    Someya, Takao; Kato, Yusaku; Sekitani, Tsuyoshi; Iba, Shingo; Noguchi, Yoshiaki; Murase, Yousuke; Kawaguchi, Hiroshi; Sakurai, Takayasu

    2005-08-01

    Skin-like sensitivity, or the capability to recognize tactile information, will be an essential feature of future generations of robots, enabling them to operate in unstructured environments. Recently developed large-area pressure sensors made with organic transistors have been proposed for electronic artificial skin (E-skin) applications. These sensors are bendable down to a 2-mm radius, a size that is sufficiently small for the fabrication of human-sized robot fingers. Natural human skin, however, is far more complex than the transistor-based imitations demonstrated so far. It performs other functions, including thermal sensing. Furthermore, without conformability, the application of E-skin on three-dimensional surfaces is impossible. In this work, we have successfully developed conformable, flexible, large-area networks of thermal and pressure sensors based on an organic semiconductor. A plastic film with organic transistor-based electronic circuits is processed to form a net-shaped structure, which allows the E-skin films to be extended by 25%. The net-shaped pressure sensor matrix was attached to the surface of an egg, and pressure images were successfully obtained in this configuration. Then, a similar network of thermal sensors was developed with organic semiconductors. Next, the possible implementation of both pressure and thermal sensors on the surfaces is presented, and, by means of laminated sensor networks, the distributions of pressure and temperature are simultaneously obtained. Author contributions: T. Someya designed research; T. Someya, Y.K., T. Sekitani, S.I., Y.N., Y.M., H.K., and T. Sakurai performed research; and T. Someya wrote the paper.This paper was submitted directly (Track II) to the PNAS office.Freely available online through the PNAS open access option.Abbreviations: E-skin, electronic artificial skin; IDS, source-drain current; PTCDI, 3,4,9,10-perylene-tetracarboxylic-diimide; parylene, polychloro-para-xylylene; CuPc, copper

  16. Progesterone-induced blocking factor differentially regulates trophoblast and tumor invasion by altering matrix metalloproteinase activity.

    PubMed

    Halasz, Melinda; Polgar, Beata; Berta, Gergely; Czimbalek, Livia; Szekeres-Bartho, Julia

    2013-12-01

    Invasiveness is a common feature of trophoblast and tumors; however, while tumor invasion is uncontrolled, trophoblast invasion is strictly regulated. Both trophoblast and tumor cells express high levels of the immunomodulatory progesterone-induced blocking factor (PIBF), therefore, we aimed to test the possibility that PIBF might be involved in invasion. To this aim, we used PIBF-silenced or PIBF-treated trophoblast (HTR8/Svneo, and primary trophoblast) and tumor (HT-1080, A549, HCT116, PC3) cell lines. Silencing of PIBF increased invasiveness as well as MMP-2,-9 secretion of HTR8/SVneo, and decreased those of HT-1080 cells. PIBF induced immediate STAT6 activation in both cell lines. Silencing of IL-4Rα abrogated all the above effects of PIBF, suggesting that invasion-related signaling by PIBF is initiated through the IL-4Rα/PIBF-receptor complex. In HTR-8/SVneo, PIBF induced fast, but transient Akt and ERK phosphorylation, whereas in tumor cells, PIBF triggered sustained Akt, ERK, and late STAT3 activation. The late signaling events might be due to indirect action of PIBF. PIBF induced the expression of EGF and HB-EGF in HT-1080 cells. The STAT3-activating effect of PIBF was reduced in HB-EGF-deficient HT-1080 cells, suggesting that PIBF-induced HB-EGF contributes to late STAT3 activation. PIBF binds to the promoters of IL-6, EGF, and HB-EGF; however, the protein profile of the protein/DNA complex is different in the two cell lines. We conclude that in tumor cells, PIBF induces proteins, which activate invasion signaling, while-based on our previous data-PIBF might control trophoblast invasion by suppressing proinvasive genes.

  17. A reconfigurable image tube using an external electronic image readout

    NASA Astrophysics Data System (ADS)

    Lapington, J. S.; Howorth, J. R.; Milnes, J. S.

    2005-08-01

    We have designed and built a sealed tube microchannel plate (MCP) intensifier for optical/NUV photon counting applications suitable for 18, 25 and 40 mm diameter formats. The intensifier uses an electronic image readout to provide direct conversion of event position into electronic signals, without the drawbacks associated with phosphor screens and subsequent optical detection. The Image Charge technique is used to remove the readout from the intensifier vacuum enclosure, obviating the requirement for additional electrical vacuum feedthroughs and for the readout pattern to be UHV compatible. The charge signal from an MCP intensifier is capacitively coupled via a thin dielectric vacuum window to the electronic image readout, which is external to the sealed intensifier tube. The readout pattern is a separate item held in proximity to the dielectric window and can be easily detached, making the system easily reconfigurable. Since the readout pattern detects induced charge and is external to the tube, it can be constructed as a multilayer, eliminating the requirement for narrow insulator gaps and allowing it to be constructed using standard PCB manufacturing tolerances. We describe two readout patterns, the tetra wedge anode (TWA), an optimized 4 electrode device similar to the wedge and strip anode (WSA) but with a factor 2 improvement in resolution, and an 8 channel high speed 50 ohm device, both manufactured as multilayer PCBs. We present results of the detector imaging performance, image resolution, linearity and stability, and discuss the development of an integrated readout and electronics device based on these designs.

  18. Read-out electronics for DC squid magnetic measurements

    DOEpatents

    Ganther, Jr., Kenneth R.; Snapp, Lowell D.

    2002-01-01

    Read-out electronics for DC SQUID sensor systems, the read-out electronics incorporating low Johnson noise radio-frequency flux-locked loop circuitry and digital signal processing algorithms in order to improve upon the prior art by a factor of at least ten, thereby alleviating problems caused by magnetic interference when operating DC SQUID sensor systems in magnetically unshielded environments.

  19. Direct readout of gaseous detectors with tiled CMOS circuits

    NASA Astrophysics Data System (ADS)

    Visschers, J. L.; Blanco Carballo, V.; Chefdeville, M.; Colas, P.; van der Graaf, H.; Schmitz, J.; Smits, S.; Timmermans, J.

    2007-03-01

    A coordinated design effort is underway, exploring the three-dimensional direct readout of gaseous detectors by an anode plate equipped with a tiled array of many CMOS pixel readout ASICs, having amplification grids integrated on their topsides and being contacted on their backside.

  20. α-Solanine inhibits human melanoma cell migration and invasion by reducing matrix metalloproteinase-2/9 activities.

    PubMed

    Lu, Ming-Kun; Shih, Yuan-Wei; Chang Chien, Tzu-Tsung; Fang, Li-Heng; Huang, Hsiang-Ching; Chen, Pin-Shern

    2010-01-01

    α-Solanine, a naturally occurring steroidal glycoalkaloid in potato sprouts, was found to possess anti-carcinogenic properties, such as inhibiting proliferation and inducing apoptosis of tumor cells. However, the effect of α-solanine on cancer metastasis remains unclear. In the present study, we examined the effect of α-solanine on metastasis in vitro. Data demonstrated that α-solanine inhibited proliferation of human melanoma cell line A2058 in a dose-dependent manner. When treated with non-toxic doses of α-solanine, cell migration and invasion were markedly suppressed. Furthermore, α-solanine reduced the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9, which are involved in the migration and invasion of cancer cells. Our biochemical assays indicated that α-solanine potently suppressed the phosphorylation of c-Jun N-terminal kinase (JNK), phosphatidylinositide-3 kinase (PI3K) and Akt, while it did not affect phosphorylation of extracellular signal regulating kinase (ERK). In addition, α-solanine significantly decreased the nuclear level of nuclear factor kappa B (NF-κB), suggesting that α-solanine inhibited NF-κB activity. Taken together, the results suggested that α-solanine inhibited migration and invasion of A2058 cells by reducing MMP-2/9 activities. It also inhibited JNK and PI3K/Akt signaling pathways as well as NF-κB activity. These findings reveal new therapeutic potential for α-solanine in anti-metastatic therapy.

  1. Performance evaluation of nonnegative matrix factorization algorithms to estimate task-related neuronal activities from fMRI data.

    PubMed

    Ding, Xiaoyu; Lee, Jong-Hwan; Lee, Seong-Whan

    2013-04-01

    Nonnegative matrix factorization (NMF) is a blind source separation (BSS) algorithm which is based on the distinct constraint of nonnegativity of the estimated parameters as well as on the measured data. In this study, according to the potential feasibility of NMF for fMRI data, the four most popular NMF algorithms, corresponding to the following two types of (1) least-squares based update [i.e., alternating least-squares NMF (ALSNMF) and projected gradient descent NMF] and (2) multiplicative update (i.e., NMF based on Euclidean distance and NMF based on divergence cost function), were investigated by using them to estimate task-related neuronal activities. These algorithms were applied firstly to individual data from a single subject and, subsequently, to group data sets from multiple subjects. On the single-subject level, although all four algorithms detected task-related activation from simulated data, the performance of multiplicative update NMFs was significantly deteriorated when evaluated using visuomotor task fMRI data, for which they failed in estimating any task-related neuronal activities. In group-level analysis on both simulated data and real fMRI data, ALSNMF outperformed the other three algorithms. The presented findings may suggest that ALSNMF appears to be the most promising option among the tested NMF algorithms to extract task-related neuronal activities from fMRI data.

  2. Large-Scale Variational Two-Electron Reduced-Density-Matrix-Driven Complete Active Space Self-Consistent Field Methods.

    PubMed

    Fosso-Tande, Jacob; Nguyen, Truong-Son; Gidofalvi, Gergely; DePrince, A Eugene

    2016-05-10

    A large-scale implementation of the complete active space self-consistent field (CASSCF) method is presented. The active space is described using the variational two-electron reduced-density-matrix (v2RDM) approach, and the algorithm is applicable to much larger active spaces than can be treated using configuration-interaction-driven methods. Density fitting or Cholesky decomposition approximations to the electron repulsion integral tensor allow for the simultaneous optimization of large numbers of external orbitals. We have tested the implementation by evaluating singlet-triplet energy gaps in the linear polyacene series and two dinitrene biradical compounds. For the acene series, we report computations that involve active spaces consisting of as many as 50 electrons in 50 orbitals and the simultaneous optimization of 1892 orbitals. For the dinitrene compounds, we find that the singlet-triplet gaps obtained from v2RDM-driven CASSCF with partial three-electron N-representability conditions agree with those obtained from configuration-interaction-driven approaches to within one-third of 1 kcal mol(-1). When enforcing only the two-electron N-representability conditions, v2RDM-driven CASSCF yields less accurate singlet-triplet energy gaps in these systems, but the quality of the results is still far superior to those obtained from standard single-reference approaches. PMID:27065086

  3. Increased expression and activation of gelatinolytic matrix metalloproteinases is associated with the progression and recurrence of human cervical cancer.

    PubMed

    Sheu, Bor-Ching; Lien, Huang-Chun; Ho, Hong-Nerng; Lin, Ho-Hsiung; Chow, Song-Nan; Huang, Su-Cheng; Hsu, Su-Ming

    2003-10-01

    Cancer-derived matrix metalloproteinases (MMPs) are proposed to be essential for tumor stromal invasion and subsequent metastasis. To explore the role of MMPs in cancer progression, we examined the expression of various MMPs and tissue inhibitors of MMPs in precancerous and cancerous lesions of the uterine cervix. Immunohistochemical studies demonstrated that MMP-2 and MMP-9 were expressed in >90% of squamous cell carcinomas (SCC) and 83-100% of high-grade squamous intraepithelial lesions (HSIL), but were less frequently expressed in low-grade squamous intraepithelial lesions and normal squamous epithelium (13%). MMP-1, MMP-14, and MMP-15 were detected in 55-81% of SCC cases, and MMP-1 was detected in 39% of HSIL. The tissue inhibitors of MMPs were weakly expressed in SCC (10-61%). By direct analysis of enzyme activities in microdissected specimens, we found that the gelatinolytic activity of MMP-9 was significantly higher in HSIL and SCC than in normal cervix (P < 0.01). The levels of active-form MMP-2 increased progressively from HSIL to SCC of stage I and more advanced stages (P < 0.01). The gelatinolytic activity of MMP-9 and active-form MMP-2 in SCC were strongly correlated with lymphovascular permeation and subsequent lymph node metastasis (P < 0.02). Moreover, the gelatinolytic activity and immunoreactive percentage of both MMP-2 and MMP-9 were significantly higher in SCC cases who had a recurrence than in those who remained free of disease (P < 0.001). Thus, our data demonstrate progressively up-regulated expression of MMP-2 and MMP-9 with SCC progression, and significant associations among their gelatinolytic activity and stage, nodal metastasis, and recurrence.

  4. Time-Domain Quaternary-Weighted Pulse Width Modulation Driving Method for Active Matrix Organic Light-Emitting Diode Displays

    NASA Astrophysics Data System (ADS)

    Park, Hyun-Sang; Kuk, Seung-Hee; Han, Min-Koo

    2008-03-01

    We proposed a new digital driving method and its pixel structure for active matrix organic light-emitting diode (AMOLED) displays employing time-domain quaternary-weighted pulse width modulation. In the new digital driving method, the luminance of AMOLED displays is accurately determined by averaging photon flux to the desired level over a frame period. The proposed pixel was verified by spice simulation and the output linearity between the grayscale and the OLED current was successfully achieved. In the proposed digital driving pixel, the timing margin was increased and the effect on luminance of AMOLED displays by the troublesome variation of the thin-film transistors (TFTs) was suppressed without additional compensation schemes.

  5. Embedded Touch Sensing Circuit Using Mutual Capacitance for Active-Matrix Organic Light-Emitting Diode Display

    NASA Astrophysics Data System (ADS)

    Park, Young-Ju; Seok, Su-Jeong; Park, Sang-Ho; Kim, Ohyun

    2011-03-01

    We propose and simulate an embedded touch sensing circuit for active-matrix organic light-emitting diode (AMOLED) displays. The circuit consists of three thin-film transistors (TFTs), one fixed capacitor, and one variable capacitor. AMOLED displays do not have a variable capacitance characteristic, so we realized a variable capacitor to detect touches in the sensing pixel by exploiting the change in the mutual capacitance between two electrodes that is caused by touch. When a dielectric substance approaches two electrodes, the electric field is shunted so that the mutual capacitance decreases. We use the existing TFT process to form the variable capacitor, so no additional process is needed. We use advanced solid-phase-crystallization TFTs because of their stability and uniformity. The proposed circuit detects multi-touch points by a scanning process.

  6. A New Low Temperature Polycrystalline Silicon Thin Film Transistor Pixel Circuit for Active Matrix Organic Light Emitting Diode

    NASA Astrophysics Data System (ADS)

    Ching-Lin Fan,; Yi-Yan Lin,; Jyu-Yu Chang,; Bo-Jhang Sun,; Yan-Wei Liu,

    2010-06-01

    This study presents one novel compensation pixel design and driving method for active matrix organic light-emitting diode (AMOLED) displays that use low-temperature polycrystalline silicon thin-film transistors (LTPS-TFTs) with a voltage feed-back method and the simulation results are proposed and verified by SPICE simulator. The measurement and simulation of LTPS TFT characteristics demonstrate the good fitting result. The proposed circuit consists of four TFTs and two capacitors with an additional signal line. The error rates of OLED anode voltage variation are below 0.3% under the threshold voltage deviation of driving TFT (Δ VTH = ± 0.33 V). The simulation results show that the pixel design can improve the display image non-uniformity by compensating the threshold voltage deviation of driving TFT and the degradation of OLED threshold voltage at the same time.

  7. A New Low Temperature Polycrystalline Silicon Thin Film Transistor Pixel Circuit for Active Matrix Organic Light Emitting Diode

    NASA Astrophysics Data System (ADS)

    Fan, Ching-Lin; Lin, Yi-Yan; Chang, Jyu-Yu; Sun, Bo-Jhang; Liu, Yan-Wei

    2010-06-01

    This study presents one novel compensation pixel design and driving method for active matrix organic light-emitting diode (AMOLED) displays that use low-temperature polycrystalline silicon thin-film transistors (LTPS-TFTs) with a voltage feed-back method and the simulation results are proposed and verified by SPICE simulator. The measurement and simulation of LTPS TFT characteristics demonstrate the good fitting result. The proposed circuit consists of four TFTs and two capacitors with an additional signal line. The error rates of OLED anode voltage variation are below 0.3% under the threshold voltage deviation of driving TFT (ΔVTH = ±0.33 V). The simulation results show that the pixel design can improve the display image non-uniformity by compensating the threshold voltage deviation of driving TFT and the degradation of OLED threshold voltage at the same time.

  8. A signal processing approach for enhanced Acoustic Emission data analysis in high activity systems: Application to organic matrix composites

    NASA Astrophysics Data System (ADS)

    Kharrat, M.; Ramasso, E.; Placet, V.; Boubakar, M. L.

    2016-03-01

    Structural elements made of Organic Matrix Composites (OMC) under complex loading may suffer from high Acoustic Emission (AE) activity caused by the emergence of different emission sources at high rates with high noise level, which finally engender continuous emissions. The detection of hits in this situation becomes a challenge particularly during fatigue tests. This work suggests an approach based on the Discrete Wavelet Transform (DWT) denoising applied on signal segments. A particular attention is paid to the adjustment of the denoising parameters based on pencil lead breaks and their influence on the quality of the denoised AE signals. The validation of the proposed approach is performed on a ring-shaped Carbon Fiber Reinforced Plastics (CFRP) under in-service-like conditions involving continuous emissions with superimposed damage-related transients. It is demonstrated that errors in hit detection are greatly reduced leading to a better identification of the natural damage scenario based on AE signals.

  9. Sequestration of nanoparticles by an EPS matrix reduces the particle-specific bactericidal activity

    PubMed Central

    Wang, Qian; Kang, Fuxing; Gao, Yanzheng; Mao, Xuewei; Hu, Xiaojie

    2016-01-01

    Most artificial nanomaterials are known to exhibit broad-spectrum bactericidal activity; however, the defence mechanisms that bacteria use based on extracellular polymeric substances (EPS) to detoxify nanoparticles (NPs) are not well known. We ruled out the possibility of ion-specific bactericidal activity by showing the lack of equivalent dissolved zinc and silicon toxicity and determined the particle-specific toxicity of ZnO and SiO2 nanoparticles (ZnONPs/SiO2NPs) through dialysis isolation experiments. Surprisingly, the manipulation of the E. coli EPS (i.e., no EPS manipulation or EPS removal by sonication/centrifugation) showed that their particle-specific bactericidal activity could be antagonized by NP-EPS sequestration. The survival rates of pristine E. coli (no EPS manipulation) reached 65% (ZnONPs, 500 mg L−1) and 79% (SiO2NPs, 500 mg L−1), whereas survival rates following EPS removal by sonication/centrifugation were 11% and 63%, respectively. Transmission electron microscopy (TEM) combined with fluorescence micro-titration analysis and Fourier-transform infrared spectroscopy (FTIR) showed that protein-like substances (N-H and C-N in amide II) and secondary carbonyl groups (C=O) in the carboxylic acids of EPS acted as important binding sites that were involved in NP sequestration. Accordingly, the amount and composition of EPS produced by bacteria have important implications for the bactericidal efficacy and potential environmental effects of NPs. PMID:26856606

  10. Activation and localization of matrix metalloproteinase-2 and -9 in the skeletal muscle of the muscular dystrophy dog (CXMDJ)

    PubMed Central

    Fukushima, Kazuhiro; Nakamura, Akinori; Ueda, Hideho; Yuasa, Katsutoshi; Yoshida, Kunihiro; Takeda, Shin'ichi; Ikeda, Shu-ichi

    2007-01-01

    Background Matrix metalloproteinases (MMPs) are key regulatory molecules in the formation, remodeling and degradation of all extracellular matrix (ECM) components in both physiological and pathological processes in various tissues. The aim of this study was to examine the involvement of gelatinase MMP family members, MMP-2 and MMP-9, in dystrophin-deficient skeletal muscle. Towards this aim, we made use of the canine X-linked muscular dystrophy in Japan (CXMDJ) model, a suitable animal model for Duchenne muscular dystrophy. Methods We used surgically biopsied tibialis cranialis muscles of normal male dogs (n = 3) and CXMDJ dogs (n = 3) at 4, 5 and 6 months of age. Muscle sections were analyzed by conventional morphological methods and in situ zymography to identify the localization of MMP-2 and MMP-9. MMP-2 and MMP-9 activity was examined by gelatin zymography and the levels of the respective mRNAs in addition to those of regulatory molecules, including MT1-MMP, TIMP-1, TIMP-2, and RECK, were analyzed by semi-quantitative RT-PCR. Results In CXMDJ skeletal muscle, multiple foci of both degenerating and regenerating muscle fibers were associated with gelatinolytic MMP activity derived from MMP-2 and/or MMP-9. In CXMDJ muscle, MMP-9 immunoreactivity localized to degenerated fibers with inflammatory cells. Weak and disconnected immunoreactivity of basal lamina components was seen in MMP-9-immunoreactive necrotic fibers of CXMDJ muscle. Gelatinolytic MMP activity observed in the endomysium of groups of regenerating fibers in CXMDJ did not co-localize with MMP-9 immunoreactivity, suggesting that it was due to the presence of MMP-2. We observed increased activities of pro MMP-2, MMP-2 and pro MMP-9, and levels of the mRNAs encoding MMP-2, MMP-9 and the regulatory molecules, MT1-MMP, TIMP-1, TIMP-2, and RECK in the skeletal muscle of CXMDJ dogs compared to the levels observed in normal controls. Conclusion MMP-2 and MMP-9 are likely involved in the pathology of dystrophin

  11. Integrated multi-crate FERA readout system

    SciTech Connect

    Kistryn, S.; Bee, C.P.; Eberhardt, P.

    1997-12-31

    We discuss a moderate-size readout system based entirely on FERA compatible units. The implementation of a specially developed FERA Extender module is presented, whose main feature is the ability to distribute the system over many CAMAC crates. This provides a convenient way of splitting the FERA bus into several virtually independent sub-systems driven by individual gate signals. Tagging of the event fragments from each sub-system with an event number incremented on the arrival of each master gate, provides a convenient means of reconstructing the full event at a later stage. An example of the external supplementary FERA control logic required for a complex multi-crate and multi-gate system controlled by a single FERA Manager, is also discussed together with some remarks on the system performance.

  12. Fast readout of carbon nanotube mechanical resonators

    NASA Astrophysics Data System (ADS)

    Meerwaldt, Harold; Singh, Vibhor; Schneider, Ben; Schouten, Raymond; van der Zant, Herre; Steele, Gary

    2013-03-01

    We perform fast readout measurements of carbon nanotube mechanical resonators. Using an electronic mixing scheme, we can detect the amplitude of the mechanical motion with an intermediate frequency (IF) of 46 MHz and a timeconstant of 1 us, up to 5 orders of magnitude faster than before. Previous measurements suffered from a low bandwidth due to the combination of the high resistance of the carbon nanotube and a large stray capacitance. We have increased the bandwidth significantly by using a high-impedance, close-proximity HEMT amplifier. The increased bandwidth should allow us to observe the nanotube's thermal motion and its transient response, approaching the regime of real-time detection of the carbon nanotube's mechanical motion.

  13. Porous poly(DL-lactic acid) matrix film with antimicrobial activities for wound dressing application.

    PubMed

    Chitrattha, Sasiprapa; Phaechamud, Thawatchai

    2016-01-01

    Poly(lactic acid) (PLA) is polymeric biomaterial that has been used for wound dressing due to its biodegradability and biocompatibility. However, PLA has some limitations including poor toughness, low degradation rate and high hydrophobicity. The aim of this study is to develop an antibiotic drug-loaded PLA porous film as wound dressing with antibacterial activity. PLA porous film was fabricated by temperature change technique using solvent casting method. Polyethylene glycol (PEG) 400 was added for improving the pore interconnectivity of film. Gentamicin sulfate (GS) or metronidazole (MZ) was incorporated into PLA porous films. PLA containing PEG 400 exhibited the more amorphous form than plain PLA film and contained 55.31 ± 2.85% porosity and 20 μm of the pore size which significantly improved the water vapor transmission rate, oxygen transmission rate, degradation rate and percentage of drug release, respectively. Drug-loaded porous films efficiently inhibited the bacteria growth. GS-loaded film inhibited Staphylococcus aureus, Proteus mirabilis, Pseudomonas aeruginosa, whereas MZ-loaded film inhibited Bacteroides fragilis and the sustainable antibacterial activity was attained for 7 days.

  14. Generation of biologically active endostatin fragments from human collagen XVIII by distinct matrix metalloproteases

    SciTech Connect

    Heljasvaara, Ritva; Nyberg, Pia; Luostarinen, Jani; Parikka, Mataleena; Heikkilae, Pia; Rehn, Marko; Sorsa, Timo; Salo, Tuula; Pihlajaniemi, Taina . E-mail: taina.pihlajaniemi@oulu.fi

    2005-07-15

    Endostatin, a potent inhibitor of endothelial cell proliferation, migration, angiogenesis and tumor growth, is proteolytically cleaved from the C-terminal noncollagenous NC1 domain of type XVIII collagen. We investigated the endostatin formation from human collagen XVIII by several MMPs in vitro. The generation of endostatin fragments differing in molecular size (24-30 kDa) and in N-terminal sequences was identified in the cases of MMP-3, -7, -9, -13 and -20. The cleavage sites were located in the protease-sensitive hinge region between the trimerization and endostatin domains of NC1. MMP-1, -2, -8 and -12 did not show any significant activity against the C-terminus of collagen XVIII. The anti-proliferative effect of the 20-kDa endostatin, three longer endostatin-containing fragments generated in vitro by distinct MMPs and the entire NC1 domain, on bFGF-stimulated human umbilical vein endothelial cells was established. The anti-migratory potential of some of these fragments was also studied. In addition, production of endostatin fragments between 24-30 kDa by human hepatoblastoma cells was shown to be due to MMP action on type XVIII collagen. Our results indicate that certain, especially cancer-related, MMP family members can generate biologically active endostatin-containing polypeptides from collagen XVIII and thus, by releasing endostatin fragments, may participate in the inhibition of endothelial cell proliferation, migration and angiogenesis.

  15. Porous poly(DL-lactic acid) matrix film with antimicrobial activities for wound dressing application.

    PubMed

    Chitrattha, Sasiprapa; Phaechamud, Thawatchai

    2016-01-01

    Poly(lactic acid) (PLA) is polymeric biomaterial that has been used for wound dressing due to its biodegradability and biocompatibility. However, PLA has some limitations including poor toughness, low degradation rate and high hydrophobicity. The aim of this study is to develop an antibiotic drug-loaded PLA porous film as wound dressing with antibacterial activity. PLA porous film was fabricated by temperature change technique using solvent casting method. Polyethylene glycol (PEG) 400 was added for improving the pore interconnectivity of film. Gentamicin sulfate (GS) or metronidazole (MZ) was incorporated into PLA porous films. PLA containing PEG 400 exhibited the more amorphous form than plain PLA film and contained 55.31 ± 2.85% porosity and 20 μm of the pore size which significantly improved the water vapor transmission rate, oxygen transmission rate, degradation rate and percentage of drug release, respectively. Drug-loaded porous films efficiently inhibited the bacteria growth. GS-loaded film inhibited Staphylococcus aureus, Proteus mirabilis, Pseudomonas aeruginosa, whereas MZ-loaded film inhibited Bacteroides fragilis and the sustainable antibacterial activity was attained for 7 days. PMID:26478412

  16. Melatonin inhibits TPA-induced oral cancer cell migration by suppressing matrix metalloproteinase-9 activation through the histone acetylation

    PubMed Central

    Yeh, Chia-Ming; Lin, Chiao-Wen; Yang, Jia-Sin; Yang, Wei-En; Su, Shih-Chi; Yang, Shun-Fa

    2016-01-01

    Melatonin exerts antimetastatic effects on liver and breast cancer and also inhibits matrix metalloproteinase (MMP) activity. However, the detailed impacts and underlying mechanisms of melatonin on oral cancer cell metastasis are still unclear. This study showed that melatonin attenuated the 12-O-tetradecanoylphorbol-13-acetate-induced migration of oral cancer cell lines, HSC-3 and OECM-1. Zymography, quantitative real-time PCR, and Western blotting analyses revealed that melatonin lessened MMP-9 enzyme activity as well as the expression of MMP-9 mRNA and protein. Furthermore, melatonin suppressed the phosphorylation of the ERK1/2 signalling pathway, which dampened MMP-9 gene transcription by affecting the expression of transcriptional coactivators, such as CREB-binding protein (CREBBP) and E1A binding protein p300 (EP300), and decreasing histone acetylation in HSC-3 and OECM-1 cells. Examinations on clinical samples exhibited that MMP-9, CREBBP, and EP300 were significantly increased in oral cancer tissues. Moreover, the relative level of CREBBP was positively correlated with the expression of MMP-9 and EP300. In conclusion, we demonstrated that melatonin inhibits the motility of HSC-3 and OECM-1 cells in vitro through a molecular mechanism that involves attenuation of MMP-9 expression and activity mediated by decreased histone acetylation. PMID:26980735

  17. Optimal level activity of matrix metalloproteinases is critical for adult visual plasticity in the healthy and stroke-affected brain

    PubMed Central

    Pielecka-Fortuna, Justyna; Kalogeraki, Evgenia; Fortuna, Michal G; Löwel, Siegrid

    2015-01-01

    The ability of the adult brain to undergo plastic changes is of particular interest in medicine, especially regarding recovery from injuries or improving learning and cognition. Matrix metalloproteinases (MMPs) have been associated with juvenile experience-dependent primary visual cortex (V1) plasticity, yet little is known about their role in this process in the adult V1. Activation of MMPs is a crucial step facilitating structural changes in a healthy brain; however, upon brain injury, upregulated MMPs promote the spread of a lesion and impair recovery. To clarify these seemingly opposing outcomes of MMP-activation, we examined the effects of MMP-inhibition on experience-induced plasticity in healthy and stoke-affected adult mice. In healthy animals, 7-day application of MMP-inhibitor prevented visual plasticity. Additionally, treatment with MMP-inhibitor once but not twice following stroke rescued plasticity, normally lost under these conditions. Our data imply that an optimal level of MMP-activity is crucial for adult visual plasticity to occur. DOI: http://dx.doi.org/10.7554/eLife.11290.001 PMID:26609811

  18. Anti-photoaging activity and inhibition of matrix metalloproteinase (MMP) by marine red alga, Corallina pilulifera methanol extract

    NASA Astrophysics Data System (ADS)

    Ryu, BoMi; Qian, Zhong-Ji; Kim, Moon-Moo; Nam, Ki Wan; Kim, Se-Kwon

    2009-02-01

    Matrix metalloproteinases (MMPs), a key component in photoaging of the skin due to exposure to ultraviolet A, appear to be increased by UV-irradiation-associated generation of reactive oxygen species (ROS). In this study, the alga Corallina pilulifera methanol (CPM) extract has been shown to exert a potent antioxidant activity and protective effect on UVA-induced oxidative stress of human dermal fibroblast (HDF) cell. Antioxidant evaluated by various antioxidant assays. These include reducing power, total antioxidant, DPPH radical scavenging, hydroxyl radical scavenging and protective effect on DNA damage caused by hydroxyl radicals generated. Further, the ROS level was detected using a fluorescence probe, 2',7'-dichlorofluorescein diacetate (DCFH-DA), which could be converted to highly fluorescent dichlorofluorescein (DCF) with the presence of intracellular ROS on HT-1080 cells. Those various antioxidant activities were compared to standard antioxidants such as α-tocopherol. In addition, the in vitro activities of MMP-2 and MMP-9 in HDF cell were inhibited by C. pilulifera methanol extract dose dependently by using gelatin zymography method. The results obtained in the present study suggested that the C. pilulifera methanol extract may be a potential source of natural anti-photoaging.

  19. Melatonin inhibits TPA-induced oral cancer cell migration by suppressing matrix metalloproteinase-9 activation through the histone acetylation.

    PubMed

    Yeh, Chia-Ming; Lin, Chiao-Wen; Yang, Jia-Sin; Yang, Wei-En; Su, Shih-Chi; Yang, Shun-Fa

    2016-04-19

    Melatonin exerts antimetastatic effects on liver and breast cancer and also inhibits matrix metalloproteinase (MMP) activity. However, the detailed impacts and underlying mechanisms of melatonin on oral cancer cell metastasis are still unclear. This study showed that melatonin attenuated the 12-O-tetradecanoylphorbol-13-acetate-induced migration of oral cancer cell lines, HSC-3 and OECM-1. Zymography, quantitative real-time PCR, and Western blotting analyses revealed that melatonin lessened MMP-9 enzyme activity as well as the expression of MMP-9 mRNA and protein. Furthermore, melatonin suppressed the phosphorylation of the ERK1/2 signalling pathway, which dampened MMP-9 gene transcription by affecting the expression of transcriptional coactivators, such as CREB-binding protein (CREBBP) and E1A binding protein p300 (EP300), and decreasing histone acetylation in HSC-3 and OECM-1 cells. Examinations on clinical samples exhibited that MMP-9, CREBBP, and EP300 were significantly increased in oral cancer tissues. Moreover, the relative level of CREBBP was positively correlated with the expression of MMP-9 and EP300. In conclusion, we demonstrated that melatonin inhibits the motility of HSC-3 and OECM-1 cells in vitro through a molecular mechanism that involves attenuation of MMP-9 expression and activity mediated by decreased histone acetylation. PMID:26980735

  20. TIMP-2 promotes activation of progelatinase A by membrane-type 1 matrix metalloproteinase immobilized on agarose beads.

    PubMed

    Kinoshita, T; Sato, H; Okada, A; Ohuchi, E; Imai, K; Okada, Y; Seiki, M

    1998-06-26

    Membrane-type 1 matrix metalloproteinase (MT1-MMP)/MMP-14 is the activator of progelatinase A (proGelA)/proMMP-2 on the cell surface. However, it was a paradox that a tissue inhibitor of metalloproteinase-2 (TIMP-2), which is an inhibitor of MT1-MMP, is required for proGelA activation by the cells expressing MT1-MMP. In this study, a truncated MT1-MMP having a FLAG-tag sequence at the C terminus (MT1-F) was immobilized onto agarose beads (MT1-F/B) and used to analyze the role of TIMP-2. The proteolytic activity of MT1-F/B against a synthetic peptide substrate was inhibited by TIMP-2 in a dose-dependent manner. In contrast, TIMP-2 promoted the processing of proGelA by MT1-F/B at low concentrations and inhibited it at higher concentrations. TIMP-2 promoted the binding of proGelA to the MT1-F on the beads by forming a trimolecular complex, which was followed by processing of proGelA. A stimulatory effect of TIMP-2 was observed under conditions in which unoccupied MT1-F was still available. Thus, the ternary complex is thought to act as a means to concentrate the substrate to the bead surface and to present it to the neighboring free MT1-F.

  1. VEGF increases the fibrinolytic activity of endothelial cells within fibrin matrices: involvement of VEGFR-2, tissue type plasminogen activator and matrix metalloproteinases.

    PubMed

    Ratel, David; Mihoubi, Samira; Beaulieu, Edith; Durocher, Yves; Rivard, Georges-Etienne; Gingras, Denis; Béliveau, Richard

    2007-01-01

    Proteolysis of fibrin matrices by endothelial cells plays essential roles in the migratory and morphogenic differentiation processes underlying angiogenesis. Using an in vitro fibrinolysis model consisting of human umbilical vein endothelial cells (HUVECs) embedded in a three dimensional fibrin matrix, we show that VEGF, an angiogenic cytokine that plays a crucial role in the onset of angiogenesis, is a potent activator of HUVEC-mediated fibrinolysis. This VEGF-dependent fibrin degradation was completely abrogated by inhibitors of either the plasminogen activator/plasmin or matrix metalloproteinases (MMP) proteolytic systems, suggesting the involvement of both classes of proteases in fibrin degradation. Accordingly, VEGF-induced fibrinolysis correlated with an increase in the expression of tPA and of some MMPs, such as MT2-MMP and was completely blocked by a neutralizing antibody against tPA. Overall, these results indicate that efficient proteolysis of three dimensional fibrin matrices during VEGF-mediated angiogenesis involves a complex interplay between the MMP and plasmin-mediated proteolytic systems. PMID:17512973

  2. Novel effects of sphingosylphosphorylcholine on invasion of breast cancer: Involvement of matrix metalloproteinase-3 secretion leading to WNT activation.

    PubMed

    Kim, Hyun Ji; Kang, Gyeoung Jin; Kim, Eun Ji; Park, Mi Kyung; Byun, Hyun Jung; Nam, Seungyoon; Lee, Ho; Lee, Chang Hoon

    2016-09-01

    Sphingosylphosphorylcholine (SPC) participates in several cellular processes including metastasis. SPC induces keratin reorganization and regulates the viscoelasticity of metastatic cancer cells including PANC-1 cancer cells leading to enhanced migration and invasion. The role of SPC and the relevant mechanism in invasion of breast cell are as yet unknown. SPC dose-dependently induces invasion of breast cancer cells or breast immortalized cells. Reverse transcription polymerase chain reaction and Western blot analyses of MCF10A and ZR-75-1 cells indicated that SPC induces expression and secretion of matrix metalloproteinase-3 (MMP3). From online KMPLOT, relapse free survival is high in patients having low MMP3 expressed basal breast cancer (n=581, p=0.032). UK370106 (MMP3 inhibitor) or gene silencing of MMP3 markedly inhibited the SPC-induced invasion of MCF10A cells. An extracellular signal-regulated kinase (ERK) inhibitor, PD98059, significantly suppressed the secretion and the gelatinolytic activity of MMP3, and invasion in MCF10A cells. Over-expression of ERK1 and ERK2 promoted both the expression and secretion of MMP3. In contrast, gene silencing of ERK1 and ERK2 attenuated the secretion of MMP3 in MCF10A cells. The effects of SPC-induced MMP3 secretion on β-catenin and TCF/lymphoid enhancer factor (LEF) promoter activity were examined since MMP3 indirectly activates canonical Wnt signaling. SPC induced translocation of β-catenin to nucleus and increased TCF/LEF promoter activity. These events were suppressed by UK370106 or PD98059. Wnt inhibitor, FH535 inhibited SPC-induced MMP3 secretion and invasion. Taken together, these results suggest that SPC induces MMP3 expression and secretion via ERK leading to Wnt activation. PMID:27216977

  3. An osteopontin-NADPH oxidase signaling cascade promotes pro-matrix metalloproteinase 9 activation in aortic mesenchymal cells.

    PubMed

    Lai, Chung-Fang; Seshadri, Venkat; Huang, Kane; Shao, Jian-Su; Cai, Jun; Vattikuti, Radhika; Schumacher, Arwyn; Loewy, Arleen P; Denhardt, David T; Rittling, Susan R; Towler, Dwight A

    2006-06-23

    Osteopontin (OPN) is a cytokine upregulated in diabetic vascular disease. To better understand its role in vascular remodeling, we assessed how OPN controls metalloproteinase (MMP) activation in aortic adventitial myofibroblasts (AMFs) and A7r5 vascular smooth muscle cells (VSMCs). By zymography, OPN and tumor necrosis factor (TNF)-alpha preferentially upregulate pro-matrix metalloproteinase 9 (pro-MMP9) activity. TNF-alpha upregulated pro-MMP9 in AMFs isolated from wild-type (OPN(+/+)) mice, but pro-MMP9 induction was abrogated in AMFs from OPN(-/-) mice. OPN treatment of VSMCs enhanced pro-MMP9 activity, and TNF-alpha induction of pro-MMP9 was inhibited by anti-OPN antibody and apocynin. Superoxide and the oxylipid product 8-isoprostaglandin F(2) alpha-isoprostane (8-IsoP) were increased by OPN treatment, and anti-OPN antibody suppressed 8-IsoP production. Like OPN and TNF-alpha, 8-IsoP preferentially activated pro-MMP9. Superoxide, 8-IsoP, and NADPH oxidase 2 (Nox2) subunits were reduced in OPN(-/-) AMFs. Treatment of A7r5 VSMCs with OPN upregulated NADPH oxidase subunit accumulation. OPN structure/function studies mapped these activities to the SVVYGLR heptapeptide motif in the thrombin-liberated human OPN N-terminal domain (SLAYGLR in mouse OPN). Treatment of aortic VSMCs with SVVYGLR upregulated pro-MMP9 activity and restored TNF-alpha activation of pro-MMP9 in OPN(-/-) AMFs. Injection of OPN-deficient OPN(+/-) mice with SVVYGLR peptide upregulated pro-MMP9 activity, 8-IsoP levels, and Nox2 protein levels in aorta and increased panmural superoxide production (dihydroethidium staining). At equivalent hyperglycemia and dyslipidemia, 8-IsoP levels and aortic pro-MMP9 were reduced with complete OPN deficiency in a model of diet-induced diabetes, achieved by comparing OPN(-/-)/LDLR(-/-) versus OPN(+/-)/LDLR(-/-) siblings. Thus, OPN provides a paracrine signal that augments vascular pro-MMP9 activity, mediated in part via superoxide generation and oxylipid

  4. Transcript-activated collagen matrix as sustained mRNA delivery system for bone regeneration.

    PubMed

    Badieyan, Zohreh Sadat; Berezhanskyy, Taras; Utzinger, Maximilian; Aneja, Manish Kumar; Emrich, Daniela; Erben, Reinhold; Schüler, Christiane; Altpeter, Philipp; Ferizi, Mehrije; Hasenpusch, Günther; Rudolph, Carsten; Plank, Christian

    2016-10-10

    Transcript therapies using chemically modified messenger RNAs (cmRNAs) are emerging as safe and promising alternatives for gene and recombinant protein therapies. However, their applications have been limited due to transient translation and relatively low stability of cmRNAs compared to DNA. Here we show that vacuum-dried cmRNA-loaded collagen sponges, termed transcript activated matrices (TAMs), can serve as depots for sustained delivery of cmRNA. TAMs provide steady state protein production for up to six days, and substantial residual expression until 11days post transfection. Another advantage of this technology was nearly 100% transfection efficiency as well as low toxicity in vitro. TAMs were stable for at least 6months at room temperature. Human BMP-2-encoding TAMs induced osteogenic differentiation of MC3T3-E1 cells in vitro and bone regeneration in a non-critical rat femoral bone defect model in vivo. In summary, TAMs are a promising tool for bone regeneration and potentially also for other applications in regenerative medicine and tissue engineering. PMID:27586186

  5. Studying the cytolytic activity of gas plasma with self-signalling phospholipid vesicles dispersed within a gelatin matrix

    NASA Astrophysics Data System (ADS)

    Marshall, Serena E.; Jenkins, A. Toby A.; Al-Bataineh, Sameer A.; Short, Robert D.; Hong, Sung-Ha; Thet, Naing T.; Oh, Jun-Seok; Bradley, James W.; Szili, Endre J.

    2013-05-01

    A synthetic biological sensor was developed to monitor the interaction of plasma with soft, hydrated biological material. It comprises phospholipid vesicles in a hydrated proteinaceous environment comprising 5% (w/v) gelatin. The vesicles contained a self-quenched dye, which was activated by vesicle destruction giving a clear fluorescent switch on. The interaction of bacterial toxins with the sensor was measured in a proof of principle experiment, then the effect of atmospheric plasma jets with the sensor, was studied in order to assess the cytolytic effect of plasma jets in biological systems. When the plasma contacted the gelatin surface perpendicular to the surface, the treatment resulted in the formation of a star-shaped pattern of microchannels that radiated out from the centre of the treatment area within the gelatin matrix, and locally damaged vesicles within the microchannels at a depth of 150 µm below the gelatin surface. Plasma jets applied in parallel to the surface of the matrix resulted in the formation of a single microchannel with damage to the vesicles only evident at the walls of the channel, and a much reduced penetration depth within the gelatin. Our data show that the effects of plasma can be deep in the gelatin material and that the angle of treatment significantly influenced the nature and level of damage to the gelatin and vesicles. Potentially this gelatin model can be used to unravel the roles of different plasma species and the direct effect of whole plasma contact, from those of primary and secondary species—i.e. primary, those emanating directly from the plasma and secondary, those species created in the ‘target’ tissue. This type of insight could be useful in the future development of safe and effective plasma medical technologies.

  6. Matrix metalloprotease activity shapes the magnitude of EPSPs and spike plasticity within the hippocampal CA3 network.

    PubMed

    Wójtowicz, Tomasz; Mozrzymas, Jerzy W

    2014-02-01

    Matrix metalloproteases (MMP) play a pivotal role in long-term synaptic plasticity, learning, and memory. The roles of different MMP subtypes are emerging, but the proteolytic activity of certain MMPs was shown to support these processes through the structural and functional modification of hippocampal Schaeffer collateral and mossy fiber (MF) synapses. However, certain patterns of synaptic activity are additionally associated with non-synaptic changes, such as the scaling of neuronal excitability. However, the extent to which MMPs affect this process remains unknown. We determined whether MMP activity interferes with excitatory post-synaptic potential EPSP-to-spike (E-S) coupling under conditions of varying synaptic activity. We evoked short- and long-term synaptic plasticity at associational/commissural (A/C) synapses of CA3 pyramidal neurons and simultaneously recorded population spikes (PSs) and EPSPs in acute rat (P30-60) brain slices in the presence of various MMP inhibitors. We found that MMP inhibition significantly reduced E-S coupling and shortened the PS latency associated with 4× 100 Hz stimulation or paired burst activity of MF-CA3 and A/C synapses. Moreover, MMP inhibition interfered with the scaling of amplitude of measured signals during high-frequency trains, thus affecting the induction of long-term potentiation (LTP). The inhibition of L-type voltage-gated calcium channels with 20 µM nifedipine or GABA-A receptors with 1-30 µM picrotoxin did not occlude the effects of MMP inhibitors. However, MMP inhibition significantly reduced the LTP of NMDA receptor-mediated EPSPs. Finally, the analysis of LTP saturation with multiple single (1× 100 Hz) or packed (4× 100 Hz) trains indicated that MMPs support E-S coupling evoked by selected synaptic activity patterns and set the ceiling for tetanically evoked E-S LTP. In conclusion, the activity of MMPs, particularly MMP-3, regulated the magnitude of EPSPs and spike plasticity in the CA3 network and may

  7. Matrix metalloproteinase-1 inhibitory activities of Morinda citrifolia seed extract and its constituents in UVA-irradiated human dermal fibroblasts.

    PubMed

    Masuda, Megumi; Murata, Kazuya; Naruto, Shunsuke; Uwaya, Akemi; Isami, Fumiyuki; Matsuda, Hideaki

    2012-01-01

    The objective of this study was to examine whether a 50% ethanolic extract (MCS-ext) of the seeds of Morinda citrifolia (noni) and its constituents have matrix metalloproteinase-1 (MMP-1) inhibitory activity in UVA-irradiated normal human dermal fibroblasts (NHDFs). The MCS-ext (10 μg/mL) inhibited MMP-1 secretion from UVA-irradiated NHDFs, without cytotoxic effects, at 48 h after UV exposure. The ethyl acetate-soluble fraction of MCS-ext was the most potent inhibitor of MMP-1 secretion. Among the constituents of the fraction, a lignan, 3,3'-bisdemethylpinoresinol (1), inhibited the MMP-1 secretion at a concentration of 0.3 μM without cytotoxic effects. Furthermore, 1 (0.3 μM) reduced the level of intracellular MMP-1 expression. Other constituents, namely americanin A (2), quercetin (3) and ursolic acid (4), were inactive. To elucidate inhibition mechanisms of MMP-1 expression and secretion, the effect of 1 on mitogen-activated protein kinases (MAPKs) phosphorylation was examined. Western blot analysis revealed that 1 (0.3 μM) reduced the phosphorylations of p38 and c-Jun-N-terminal kinase (JNK). These results suggested that 1 suppresses intracellular MMP-1 expression, and consequent secretion from UVA-irradiated NHDFs, by down-regulation of MAPKs phosphorylation.

  8. Matrix-addressable, active electrode arrays for neural stimulation using organic semiconductors—cytotoxicity and pilot experiments in vivo

    NASA Astrophysics Data System (ADS)

    Feili, Dara; Schuettler, Martin; Stieglitz, Thomas

    2008-03-01

    Organic field effect transistors can be integrated into micromachined polyimide-based neural stimulation electrode arrays in order to build active switching matrices. With this approach, a matrix of N × M electrode contacts requires only N + M interconnects to a stimulator when active switching elements are used instead of N × M interconnects. In this paper, we demonstrated that pentacene-based organic field effect transistors (OFETs) can be used to drive stimulation currents through neural electrodes in a physiological-like environment. In order to prove the general applicability as an implant material, the cytotoxicity of pentacene was evaluated with respect to potential effects on cell viability. The results of these tests indicate that extracts from pentacene inhibit neither proliferation nor metabolism of the tested mouse fibroblasts. However, some effect on cell spreading was observed when cells were in direct contact to pentacene for 48 h. In pilot experiments it was demonstrated for the very first time that pentacene transistors can be used as switching elements, acting as voltage-controlled current sources, capable of driving currents suitable for electrical stimulation of a peripheral nerve via a tripolar cuff electrode.

  9. Fumigaclavine C, an fungal metabolite, improves experimental colitis in mice via downregulating Th1 cytokine production and matrix metalloproteinase activity.

    PubMed

    Wu, Xue-Feng; Fei, Ming-Jian; Shu, Ren-Geng; Tan, Ren-Xiang; Xu, Qiang

    2005-09-01

    In the present paper, the effect of Fumigaclavine C, a fungal metabolite, on experimental colitis was examined. Fumigaclavine C, when administered intraperitoneally once a day, significantly reduced the weight loss and mortality rate of mice with experimental colitis induced by intrarectally injection of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). This compound also markedly alleviated the macroscopic and microscopic appearances of colitis. Furthermore, Fumigaclavine C, given both in vivo and in vitro, showed a marked inhibition on the expression of several inflammatory cytokines, including IL-1beta, IL-2, IL-12alpha, IFN-gamma, TNF-alpha as well as MMP-9 in sacral lymph node cells, colonic patch lymphocytes and colitis tissues from the TNBS colitis mice. Meanwhile, the compound caused a dose-dependent reduction in IL-2 and IFN-gamma from the lymphocytes at the protein level and MMP-9 activity. These results suggest that Fumigaclavine C may alleviate experimental colitis mainly via down-regulating the production of Th1 cytokines and the activity of matrix metalloproteinase. PMID:16023606

  10. Fluid Shear Stress Regulates the Invasive Potential of Glioma Cells via Modulation of Migratory Activity and Matrix Metalloproteinase Expression

    PubMed Central

    Qazi, Henry; Shi, Zhong-Dong; Tarbell, John M.

    2011-01-01

    Background Glioma cells are exposed to elevated interstitial fluid flow during the onset of angiogenesis, at the tumor periphery while invading normal parenchyma, within white matter tracts, and during vascular normalization therapy. Glioma cell lines that have been exposed to fluid flow forces in vivo have much lower invasive potentials than in vitro cell motility assays without flow would indicate. Methodology/Principal Findings A 3D Modified Boyden chamber (Darcy flow through collagen/cell suspension) model was designed to mimic the fluid dynamic microenvironment to study the effects of fluid shear stress on the migratory activity of glioma cells. Novel methods for gel compaction and isolation of chemotactic migration from flow stimulation were utilized for three glioma cell lines: U87, CNS-1, and U251. All physiologic levels of fluid shear stress suppressed the migratory activity of U87 and CNS-1 cell lines. U251 motility remained unaltered within the 3D interstitial flow model. Matrix Metalloproteinase (MMP) inhibition experiments and assays demonstrated that the glioma cells depended on MMP activity to invade, and suppression in motility correlated with downregulation of MMP-1 and MMP-2 levels. This was confirmed by RT-PCR and with the aid of MMP-1 and MMP-2 shRNA constructs. Conclusions/Significance Fluid shear stress in the tumor microenvironment may explain reduced glioma invasion through modulation of cell motility and MMP levels. The flow-induced migration trends were consistent with reported invasive potentials of implanted gliomas. The models developed for this study imply that flow-modulated motility involves mechanotransduction of fluid shear stress affecting MMP activation and expression. These models should be useful for the continued study of interstitial flow effects on processes that affect tumor progression. PMID:21637818

  11. SiPM based readout system for PbWO4 crystals

    NASA Astrophysics Data System (ADS)

    Berra, A.; Bolognini, D.; Bonfanti, S.; Bonvicini, V.; Lietti, D.; Penzo, A.; Prest, M.; Stoppani, L.; Vallazza, E.

    2013-08-01

    Silicon PhotoMultipliers (SiPMs) consist of a matrix of small passively quenched silicon avalanche photodiodes operated in limited Geiger-mode (GM-APDs) and read out in parallel from a common output node. Each pixel (with a typical size in the 20-100 μm range) gives the same current response when hit by a photon; the SiPM output signal is the sum of the signals of all the pixels, which depends on the light intensity. The main advantages of SiPMs with respect to photomultiplier tubes (PMTs) are essentially the small dimensions, the insensitivity to magnetic fields and a low bias voltage. This contribution presents the performance of a SiPM based readout system for crystal calorimeters developed in the framework of the FACTOR/TWICE collaboration. The SiPM used for the test is a new device produced by FBK-irst which consists in a matrix of four sensors embedded in the same silicon substrate, called QUAD. The SiPM has been coupled to a lead tungstate crystal, an early-prototype version of the crystals developed for the electromagnetic calorimeter of the CMS experiment. New tests are foreseen using a complete module consisting of nine crystals, each one readout by two QUADs.

  12. Hybrid matrix amplifier

    DOEpatents

    Martens, J.S.; Hietala, V.M.; Plut, T.A.

    1995-01-03

    The present invention comprises a novel matrix amplifier. The matrix amplifier includes an active superconducting power divider (ASPD) having N output ports; N distributed amplifiers each operatively connected to one of the N output ports of the ASPD; and a power combiner having N input ports each operatively connected to one of the N distributed amplifiers. The distributed amplifier can included M stages of amplification by cascading superconducting active devices. The power combiner can include N active elements. The resulting (N[times]M) matrix amplifier can produce signals of high output power, large bandwidth, and low noise. 6 figures.

  13. Hybrid matrix amplifier

    DOEpatents

    Martens, Jon S.; Hietala, Vincent M.; Plut, Thomas A.

    1995-01-01

    The present invention comprises a novel matrix amplifier. The matrix amplifier includes an active superconducting power divider (ASPD) having N output ports; N distributed amplifiers each operatively connected to one of the N output ports of the ASPD; and a power combiner having N input ports each operatively connected to one of the N distributed amplifiers. The distributed amplifier can included M stages of amplification by cascading superconducting active devices. The power combiner can include N active elements. The resulting (N.times.M) matrix amplifier can produce signals of high output power, large bandwidth, and low noise.

  14. Activated hepatic stellate cells are dependent on self-collagen, cleaved by membrane type 1 matrix metalloproteinase for their growth.

    PubMed

    Birukawa, Naoko Kubo; Murase, Kazuyuki; Sato, Yasushi; Kosaka, Akemi; Yoneda, Akihiro; Nishita, Hiroki; Fujita, Ryosuke; Nishimura, Miyuki; Ninomiya, Takafumi; Kajiwara, Keiko; Miyazaki, Miyono; Nakashima, Yusuke; Ota, Sigenori; Murakami, Yuya; Tanaka, Yasunobu; Minomi, Kenjiro; Tamura, Yasuaki; Niitsu, Yoshiro

    2014-07-18

    Stellate cells are distributed throughout organs, where, upon chronic damage, they become activated and proliferate to secrete collagen, which results in organ fibrosis. An intriguing property of hepatic stellate cells (HSCs) is that they undergo apoptosis when collagen is resolved by stopping tissue damage or by treatment, even though the mechanisms are unknown. Here we disclose the fact that HSCs, normal diploid cells, acquired dependence on collagen for their growth during the transition from quiescent to active states. The intramolecular RGD motifs of collagen were exposed by cleavage with their own membrane type 1 matrix metalloproteinase (MT1-MMP). The following evidence supports this conclusion. When rat activated HSCs (aHSCs) were transduced with siRNA against the collagen-specific chaperone gp46 to inhibit collagen secretion, the cells underwent autophagy followed by apoptosis. Concomitantly, the growth of aHSCs was suppressed, whereas that of quiescent HSCs was not. These in vitro results are compatible with the in vivo observation that apoptosis of aHSCs was induced in cirrhotic livers of rats treated with siRNAgp46. siRNA against MT1-MMP and addition of tissue inhibitor of metalloproteinase 2 (TIMP-2), which mainly inhibits MT1-MMP, also significantly suppressed the growth of aHSCs in vitro. The RGD inhibitors echistatin and GRGDS peptide and siRNA against the RGD receptor αVβ1 resulted in the inhibition of aHSCs growth. Transduction of siRNAs against gp46, αVβ1, and MT1-MMP to aHSCs inhibited the survival signal of PI3K/AKT/IκB. These results could provide novel antifibrosis strategies.

  15. Neovibsanin B increases extracellular matrix proteins in optic nerve head cells via activation of Smad signalling pathway.

    PubMed

    Wang, Zhen; Xu, Wei; Rong, Ao; Lin, Yan; Qiu, Xu-Ling; Qu, Shen; Lan, Xian-Hai

    2015-01-01

    The present study demonstrates the effect of neovibsanin B on the synthesis and deposition of ECM proteins and the signalling pathways used in optic nerve head (ONH) astrocytes and lamina cribrosa (LC) cells. For investigation of the signalling pathway used by neovibsanin B, ONH cells were treated with neovibsanin B. Western blot and immunostaining analyses were used to examine the phosphorylation of proteins involved in Smad and non-Smad signalling pathway. The results revealed that ONH cells on treatment with neovibsanin B showed enhanced synthesis of extracellular matrix (ECM) proteins. Neovibsanin B induced phosphorylation of canonical signalling proteins, Smad2/3. However phosphorylation of non-canonical signalling proteins, extracellular signal-regulated kinases, p38, and c-Jun N-terminal kinases (JNK) 1/2 remained unaffected. There was also increase in co-localization of pSmad2/3 with Co-Smad4 in the nucleus of ONH astrocytes and LC cells indicating activation of the canonical Smad signalling pathway. Treatment of ONH cells with SIS3, inhibitor of Smad3 phosphorylation reversed the neovibsanin B stimulated ECM expression as well as activation of canonical pathway signalling molecules. In addition, inhibition of Smad2 or Smad3 using small interfering RNA (siRNA) also suppressed neovibsanin B stimulated ECM protein synthesis in ONH astrocytes and LC cells. Thus neovibsanin B utilizes the canonical Smad signalling pathway to stimulate ECM synthesis in human ONH cells. The neovibsanin B induced ECM synthesis and activation of the canonical Smad signalling pathway may be due to its effect on transforming growth factor-β2 (TGF-β2). However, further studies are under process to understand the mechanism.

  16. Interleukin-1{beta} regulates cell proliferation and activity of extracellular matrix remodelling enzymes in cultured primary pig heart cells

    SciTech Connect

    Zitta, Karina; Brandt, Berenice; Wuensch, Annegret; Meybohm, Patrick; Bein, Berthold; Steinfath, Markus; Scholz, Jens; Albrecht, Martin

    2010-09-03

    Research highlights: {yields} Levels of IL-1{beta} are increased in the pig myocardium after infarction. {yields} Cultured pig heart cells possess IL-1 receptors. {yields} IL-1{beta} increases cell proliferation of pig heart cells in-vitro. {yields} IL-1{beta} increases MMP-2 and MMP-9 activity in pig heart cells in-vitro. {yields} IL-1{beta} may be important for tissue remodelling events after myocardial infarction. -- Abstract: After myocardial infarction, elevated levels of interleukins (ILs) are found within the myocardial tissue and IL-1{beta} is considered to play a major role in tissue remodelling events throughout the body. In the study presented, we have established a cell culture model of primary pig heart cells to evaluate the effects of different concentrations of IL-1{beta} on cell proliferation as well as expression and activity of enzymes typically involved in tissue remodelling. Primary pig heart cell cultures were derived from three different animals and stimulated with recombinant pig IL-1{beta}. RNA expression was detected by RT-PCR, protein levels were evaluated by Western blotting, activity of matrix metalloproteinases (MMPs) was quantified by gelatine zymography and cell proliferation was measured using colorimetric MTS assays. Pig heart cells express receptors for IL-1 and application of IL-1{beta} resulted in a dose-dependent increase of cell proliferation (P < 0.05 vs. control; 100 ng/ml; 24 h). Gene expression of caspase-3 was increased by IL-1{beta} (P < 0.05 vs. control; 100 ng/ml; 3 h), and pro-caspase-3 but not active caspase was detected in lysates of pig heart cells by Western blotting. MMP-2 gene expression as well as enzymatic activities of MMP-2 and MMP-9 were increased by IL-1{beta} (P < 0.05 vs. control; 100 ng/ml; 3 h for gene expression, 48 and 72 h for enzymatic activities of MMP-2 and MMP-9, respectively). Our in vitro data suggest that IL-1{beta} plays a major role in the events of tissue remodelling in the heart. Combined

  17. Red Grape Skin Polyphenols Blunt Matrix Metalloproteinase-2 and -9 Activity and Expression in Cell Models of Vascular Inflammation: Protective Role in Degenerative and Inflammatory Diseases.

    PubMed

    Calabriso, Nadia; Massaro, Marika; Scoditti, Egeria; Pellegrino, Mariangela; Ingrosso, Ilaria; Giovinazzo, Giovanna; Carluccio, Maria Annunziata

    2016-08-29

    Matrix metalloproteinases (MMPs) are endopeptidases responsible for the hydrolysis of various components of extracellular matrix. MMPs, namely gelatinases MMP-2 and MMP-9, contribute to the progression of chronic and degenerative diseases. Since gelatinases' activity and expression are regulated by oxidative stress, we sought to evaluate whether supplementation with polyphenol-rich red grape skin extracts modulated the matrix-degrading capacity in cell models of vascular inflammation. Human endothelial and monocytic cells were incubated with increasing concentrations (0.5-25 μg/mL) of Negroamaro and Primitivo red grape skin polyphenolic extracts (NSPE and PSPE, respectively) or their specific components (0.5-25 μmol/L), before stimulation with inflammatory challenge. NSPE and PSPE inhibited, in a concentration-dependent manner, endothelial invasion as well as the MMP-9 and MMP-2 release in stimulated endothelial cells, and MMP-9 production in inflamed monocytes, without affecting tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2. The matrix degrading inhibitory capacity was the same for both NSPE and PSPE, despite their different polyphenolic profiles. Among the main polyphenols of grape skin extracts, trans-resveratrol, trans-piceid, kaempferol and quercetin exhibited the most significant inhibitory effects on matrix-degrading enzyme activities. Our findings appreciate the grape skins as rich source of polyphenols able to prevent the dysregulation of vascular remodelling affecting degenerative and inflammatory diseases.

  18. Red Grape Skin Polyphenols Blunt Matrix Metalloproteinase-2 and -9 Activity and Expression in Cell Models of Vascular Inflammation: Protective Role in Degenerative and Inflammatory Diseases.

    PubMed

    Calabriso, Nadia; Massaro, Marika; Scoditti, Egeria; Pellegrino, Mariangela; Ingrosso, Ilaria; Giovinazzo, Giovanna; Carluccio, Maria Annunziata

    2016-01-01

    Matrix metalloproteinases (MMPs) are endopeptidases responsible for the hydrolysis of various components of extracellular matrix. MMPs, namely gelatinases MMP-2 and MMP-9, contribute to the progression of chronic and degenerative diseases. Since gelatinases' activity and expression are regulated by oxidative stress, we sought to evaluate whether supplementation with polyphenol-rich red grape skin extracts modulated the matrix-degrading capacity in cell models of vascular inflammation. Human endothelial and monocytic cells were incubated with increasing concentrations (0.5-25 μg/mL) of Negroamaro and Primitivo red grape skin polyphenolic extracts (NSPE and PSPE, respectively) or their specific components (0.5-25 μmol/L), before stimulation with inflammatory challenge. NSPE and PSPE inhibited, in a concentration-dependent manner, endothelial invasion as well as the MMP-9 and MMP-2 release in stimulated endothelial cells, and MMP-9 production in inflamed monocytes, without affecting tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2. The matrix degrading inhibitory capacity was the same for both NSPE and PSPE, despite their different polyphenolic profiles. Among the main polyphenols of grape skin extracts, trans-resveratrol, trans-piceid, kaempferol and quercetin exhibited the most significant inhibitory effects on matrix-degrading enzyme activities. Our findings appreciate the grape skins as rich source of polyphenols able to prevent the dysregulation of vascular remodelling affecting degenerative and inflammatory diseases. PMID:27589705

  19. Scalar Readout Model for Super-Rens Focused Spot

    NASA Astrophysics Data System (ADS)

    Assafrao, A. C.; Pereira, S. F.; Urbach, H. P.

    2011-12-01

    A scalar readout model is presented to investigate the readout characteristics of the super resolution near field (SRens) disc. The super resolution effect is described by means of a threshold model, where the super resolution material imparts a phase change on the focused spot if the laser density energy is high enough to trigger the SRens effect. This approach results in a very fast way of computing the basic characteristics of the SRens readout signal, being suitable for large investigations. Moreover, many simulation results have been experimentally confirmed by other groups, which further validates the model. Thus, this simplified model is an useful tool for a better comprehension of the readout signal of the super resolution effect in optical data storage and other super resolution applications.

  20. TES Detector Noise Limited Readout Using SQUID Multiplexers

    NASA Technical Reports Server (NTRS)

    Staguhn, J. G.; Benford, D. J.; Chervenak, J. A.; Khan, S. A.; Moseley, S. H.; Shafer, R. A.; Deiker, S.; Grossman, E. N.; Hilton, G. C.; Irwin, K. D.

    2004-01-01

    The availability of superconducting Transition Edge Sensors (TES) with large numbers of individual detector pixels requires multiplexers for efficient readout. The use of multiplexers reduces the number of wires needed between the cryogenic electronics and the room temperature electronics and cuts the number of required cryogenic amplifiers. We are using an 8 channel SQUID multiplexer to read out one-dimensional TES arrays which are used for submillimeter astronomical observations. We present results from test measurements which show that the low noise level of the SQUID multiplexers allows accurate measurements of the TES Johnson noise, and that in operation, the readout noise is dominated by the detector noise. Multiplexers for large number of channels require a large bandwidth for the multiplexed readout signal. We discuss the resulting implications for the noise performance of these multiplexers which will be used for the readout of two dimensional TES arrays in next generation instruments.

  1. Focal plane infrared readout circuit with automatic background suppression

    NASA Technical Reports Server (NTRS)

    Pain, Bedabrata (Inventor); Yang, Guang (Inventor); Sun, Chao (Inventor); Shaw, Timothy J. (Inventor); Wrigley, Chris J. (Inventor)

    2002-01-01

    A circuit for reading out a signal from an infrared detector includes a current-mode background-signal subtracting circuit having a current memory which can be enabled to sample and store a dark level signal from the infrared detector during a calibration phase. The signal stored by the current memory is subtracted from a signal received from the infrared detector during an imaging phase. The circuit also includes a buffered direct injection input circuit and a differential voltage readout section. By performing most of the background signal estimation and subtraction in a current mode, a low gain can be provided by the buffered direct injection input circuit to keep the gain of the background signal relatively small, while a higher gain is provided by the differential voltage readout circuit. An array of such readout circuits can be used in an imager having an array of infrared detectors. The readout circuits can provide a high effective handling capacity.

  2. Single-Readout High-Density Memristor Crossbar

    NASA Astrophysics Data System (ADS)

    Zidan, M. A.; Omran, H.; Naous, R.; Sultan, A.; Fahmy, H. A. H.; Lu, W. D.; Salama, K. N.

    2016-01-01

    High-density memristor-crossbar architecture is a very promising technology for future computing systems. The simplicity of the gateless-crossbar structure is both its principal advantage and the source of undesired sneak-paths of current. This parasitic current could consume an enormous amount of energy and ruin the readout process. We introduce new adaptive-threshold readout techniques that utilize the locality and hierarchy properties of the computer-memory system to address the sneak-paths problem. The proposed methods require a single memory access per pixel for an array readout. Besides, the memristive crossbar consumes an order of magnitude less power than state-of-the-art readout techniques.

  3. Single-Readout High-Density Memristor Crossbar

    PubMed Central

    Zidan, M. A.; Omran, H.; Naous, R.; Sultan, A.; Fahmy, H. A. H.; Lu, W. D.; Salama, K. N.

    2016-01-01

    High-density memristor-crossbar architecture is a very promising technology for future computing systems. The simplicity of the gateless-crossbar structure is both its principal advantage and the source of undesired sneak-paths of current. This parasitic current could consume an enormous amount of energy and ruin the readout process. We introduce new adaptive-threshold readout techniques that utilize the locality and hierarchy properties of the computer-memory system to address the sneak-paths problem. The proposed methods require a single memory access per pixel for an array readout. Besides, the memristive crossbar consumes an order of magnitude less power than state-of-the-art readout techniques. PMID:26738564

  4. Single-Readout High-Density Memristor Crossbar.

    PubMed

    Zidan, M A; Omran, H; Naous, R; Sultan, A; Fahmy, H A H; Lu, W D; Salama, K N

    2016-01-07

    High-density memristor-crossbar architecture is a very promising technology for future computing systems. The simplicity of the gateless-crossbar structure is both its principal advantage and the source of undesired sneak-paths of current. This parasitic current could consume an enormous amount of energy and ruin the readout process. We introduce new adaptive-threshold readout techniques that utilize the locality and hierarchy properties of the computer-memory system to address the sneak-paths problem. The proposed methods require a single memory access per pixel for an array readout. Besides, the memristive crossbar consumes an order of magnitude less power than state-of-the-art readout techniques.

  5. Balanced homodyne readout for quantum limited gravitational wave detectors.

    PubMed

    Fritschel, Peter; Evans, Matthew; Frolov, Valery

    2014-02-24

    Balanced homodyne detection is typically used to measure quantum-noise-limited optical beams, including squeezed states of light, at audio-band frequencies. Current designs of advanced gravitational wave interferometers use some type of homodyne readout for signal detection, in part because of its compatibility with the use of squeezed light. The readout scheme used in Advanced LIGO, called DC readout, is however not a balanced detection scheme. Instead, the local oscillator field, generated from a dark fringe offset, co-propagates with the signal field at the anti-symmetric output of the beam splitter. This article examines the alternative of a true balanced homodyne detection for the readout of gravitational wave detectors such as Advanced LIGO. Several practical advantages of the balanced detection scheme are described. PMID:24663746

  6. Structural Characterization of Sputtered Silicon Thin Films after Rapid Thermal Annealing for Active-Matrix Organic Light Emitting Diode

    NASA Astrophysics Data System (ADS)

    Mugiraneza, Jean de Dieu; Miyahira, Tomoyuki; Sakamoto, Akinori; Chen, Yi; Okada, Tatsuya; Noguchi, Takashi; Itoh, Taketsugu

    2010-12-01

    The microcrystalline phase obtained by adopting a two-step rapid thermal annealing (RTA) process for rf-sputtered silicon films deposited on thermally durable glass was characterized. The optical properties, surface morphology, and internal stress of the annealed Si films are investigated. As the thermally durable glass substrate allows heating of the deposited films at high temperatures, micro-polycrystalline silicon (micro-poly-Si) films of uniform grain size with a smooth surface and a low internal stress could be obtained after annealing at 750 °C. The thermal stress in the Si films was 100 times lower than that found in the films deposited on conventional glass. Uniform grains with an average grain size of 30 nm were observed by transmission electron microscopy (TEM) in the films annealed at 800 °C. These micro-poly-Si films have potential application for fabrication of uniform and reliable thin film transistors (TFTs) for large scale active-matrix organic light emitting diode (AMOLED) displays.

  7. 3.4-Inch Quarter High Definition Flexible Active Matrix Organic Light Emitting Display with Oxide Thin Film Transistor

    NASA Astrophysics Data System (ADS)

    Hatano, Kaoru; Chida, Akihiro; Okano, Tatsuya; Sugisawa, Nozomu; Inoue, Tatsunori; Seo, Satoshi; Suzuki, Kunihiko; Oikawa, Yoshiaki; Miyake, Hiroyuki; Koyama, Jun; Yamazaki, Shunpei; Eguchi, Shingo; Katayama, Masahiro; Sakakura, Masayuki

    2011-03-01

    In this paper, we report a 3.4-in. flexible active matrix organic light emitting display (AMOLED) display with remarkably high definition (quarter high definition: QHD) in which oxide thin film transistors (TFTs) are used. We have developed a transfer technology in which a TFT array formed on a glass substrate is separated from the substrate by physical force and then attached to a flexible plastic substrate. Unlike a normal process in which a TFT array is directly fabricated on a thin plastic substrate, our transfer technology permits a high integration of high performance TFTs, such as low-temperature polycrystalline silicon TFTs (LTPS TFTs) and oxide TFTs, on a plastic substrate, because a flat, rigid, and thermally-stable glass substrate can be used in the TFT fabrication process in our transfer technology. As a result, this technology realized an oxide TFT array for an AMOLED on a plastic substrate. Furthermore, in order to achieve a high-definition AMOLED, color filters were incorporated in the TFT array and a white organic light-emitting diode (OLED) was combined. One of the features of this device is that the whole body of the device can be bent freely because a source driver and a gate driver can be integrated on the substrate due to the high mobility of an oxide TFT. This feature means “true” flexibility.

  8. A High-Performance Current-Mode Source Driver IC for Mobile Active Matrix Organic Light Emitting Diode Displays

    NASA Astrophysics Data System (ADS)

    Jeong, Il-Hun; Kwon, Oh-Kyong

    2008-03-01

    In this paper, we describe two types of 8-bit current-mode driver ICs with a small area and good performance for applications high accuracy current-mode digital-to-analog converters (DACs), and improved channel-to-channel uniformity for active matrix organic light-emitting diode (AMOLED) displays. One uses the proposed current steering DAC (type A), which is an improved architecture of a binary-weighted DAC, and the other uses a DAC that is a combination of a thermometer-decoded of the DAC and a binary-weighted type. The measured results show that the peak integral nonlinearity (INL) is within ±0.5 the least significant bit (LSB), the peak differential nonlinearity (DNL) is within ±0.5 LSB, and the nonuniformity of output current among channels and chips is within ±0.5 LSB. The size of the driver IC is 15,820 ×1,500 µm2 and the total power consumption of the current-mode driver IC is less than 9 mW when the display has full-white pattern with a luminance of 150 cd/m2. The chip area and power consumption with the proposed current DAC are reduced by 26 and 10%, respectively, compared with those of conventional driver ICs with a fully binary-weighted DAC.

  9. Investigation of Pattern-Induced Brightness Non-uniformity in Active-Matrix Organic Light-Emitting Diode Displays

    NASA Astrophysics Data System (ADS)

    Kim, Kyoung-Bo; Park, Hye-Hyang; Kwon, Ohseob; Kim, Moojin; Lee, Ki-Yong; Park, Yongwoo; Choi, JongHyun; Yu, CheolHo; Kim, Hye-Dong; Kim, Sung Chul; Chung, Ho-Kyoon

    2008-01-01

    We recently improved the brightness non-uniformity in active-matrix organic light-emitting diode (AMOLED) regarding non-uniform laser energy distribution by applying a “shot mixing” technique in sequential lateral solidification (SLS) method. Although the new SLS technique was employed, another brightness non-uniformity that appeared as oblique lines on AMOLED panels became a crucial issue. In this work, we attempted to investigate the origins of the non-uniformity. Our systematic analysis on the oblique lines revealed that the line type non-uniformity was attributed to both the SLS process and the thin-film transistor (TFT) fabrication processes. In particular, we found that such oblique patterns might be related to moiré patterns that appear when primary grain boundaries aligned in a repetitive pattern is placed over other repetitive TFT patterns such as metal lines. We adopted a method to diminish the moiré pattern type non-uniformity by applying top emission TFT structure.

  10. A flexible organic active matrix circuit fabricated using novel organic thin film transistors and organic light-emitting diodes

    NASA Astrophysics Data System (ADS)

    Gutiérrez-Heredia, G.; González, L. A.; Alshareef, H. N.; Gnade, B. E.; Quevedo-López, M.

    2010-11-01

    We present an active matrix circuit fabricated on plastic (polyethylene naphthalene, PEN) and glass substrates using organic thin film transistors and organic capacitors to control organic light-emitting diodes (OLEDs). The basic circuit is fabricated using two pentacene-based transistors and a capacitor using a novel aluminum oxide/parylene stack (Al2O3/parylene) as the dielectric for both the transistor and the capacitor. We report that our circuit can deliver up to 15 µA to each OLED pixel. To achieve 200 cd m-2 of brightness a 10 µA current is needed; therefore, our approach can initially deliver 1.5× the required current to drive a single pixel. In contrast to parylene-only devices, the Al2O3/parylene stack does not fail after stressing at a field of 1.7 MV cm-1 for >10 000 s, whereas 'parylene only' devices show breakdown at approximately 1000 s. Details of the integration scheme are presented.

  11. Optimal Topology and Experimental Evaluation of Piezoelectric Materials for Actively Shunted General Electric Polymer Matrix Fiber Composite Blades

    NASA Technical Reports Server (NTRS)

    Choi, Benjamin B.; Duffy, Kirsten; Kauffman, Jeffrey L.; Kray, Nicholas

    2012-01-01

    NASA Glenn Research Center, in collaboration with GE Aviation, has begun the development of a smart adaptive structure system with piezoelectric (PE) transducers to improve composite fan blade damping at resonances. Traditional resonant damping approaches may not be realistic for rotating frame applications such as engine blades. The limited space in which the blades reside in the engine makes it impossible to accommodate the circuit size required to implement passive resonant damping. Thus, a novel digital shunt scheme has been developed to replace the conventional electric passive shunt circuits. The digital shunt dissipates strain energy through the load resistor on a power amplifier. General Electric (GE) designed and fabricated a variety of polymer matrix fiber composite (PMFC) test specimens. Investigating the optimal topology of PE sensors and actuators for each test specimen has revealed the best PE transducer location for each target mode. Also a variety of flexible patches, which can conform to the blade surface, have been tested to identify the best performing PE patch. The active damping control achieved significant performance at target modes. This work has been highlighted by successful spin testing up to 5000 rpm of subscale GEnx composite blades in Glenn s Dynamic Spin Rig.

  12. Active site specificity profiling datasets of matrix metalloproteinases (MMPs) 1, 2, 3, 7, 8, 9, 12, 13 and 14

    PubMed Central

    Eckhard, Ulrich; Huesgen, Pitter F.; Schilling, Oliver; Bellac, Caroline L.; Butler, Georgina S.; Cox, Jennifer H.; Dufour, Antoine; Goebeler, Verena; Kappelhoff, Reinhild; auf dem Keller, Ulrich; Klein, Theo; Lange, Philipp F.; Marino, Giada; Morrison, Charlotte J.; Prudova, Anna; Rodriguez, David; Starr, Amanda E.; Wang, Yili; Overall, Christopher M.

    2016-01-01

    The data described provide a comprehensive resource for the family-wide active site specificity portrayal of the human matrix metalloproteinase family. We used the high-throughput proteomic technique PICS (Proteomic Identification of protease Cleavage Sites) to comprehensively assay 9 different MMPs. We identified more than 4300 peptide cleavage sites, spanning both the prime and non-prime sides of the scissile peptide bond allowing detailed subsite cooperativity analysis. The proteomic cleavage data were expanded by kinetic analysis using a set of 6 quenched-fluorescent peptide substrates designed using these results. These datasets represent one of the largest specificity profiling efforts with subsequent structural follow up for any protease family and put the spotlight on the specificity similarities and differences of the MMP family. A detailed analysis of this data may be found in Eckhard et al. (2015) [1]. The raw mass spectrometry data and the corresponding metadata have been deposited in PRIDE/ProteomeXchange with the accession number PXD002265. PMID:26981551

  13. Activated matrix metalloproteinase-8 in saliva as diagnostic test for periodontal disease? A case-control study.

    PubMed

    Izadi Borujeni, Susan; Mayer, Matthias; Eickholz, Peter

    2015-12-01

    Untreated periodontal disease may influence general health. However, how may a physician, who is not trained in periodontal probing, detect untreated periodontitis? Activated matrix metalloproteinase-8 (aMMP-8) in saliva correlates with periodontal probing parameters. Thus, sensitivity and specificity of a chair-side test for aMMP-8 to detect periodontitis were evaluated. Thirty cases [untreated chronic periodontitis (ChP); 15 generalized moderate and 15 generalized severe] and 30 controls [probing depths (PD) ≤3 mm, vertical probing attachment level (PAL-V) ≤2 mm at <30 % of sites) were examined periodontally (PD, PAL-V, bleeding on probing). Subsequently, the aMMP-8 test was performed. The test kit becomes positive with ≥25 ng/ml aMMP-8 in the sample. The aMMP-8 test was positive in 87 % of ChP and in 40 % of controls. That corresponds to a sensitivity of 87 % and a specificity of 60 %. The sensitivity to detect generalized severe ChP was 93 % (60 % specificity). Backward stepwise logistic regression analysis to explain positive aMMP-8 tests identified exclusively ChP with an odds ratio of 9.8 (p < 0.001). Positive results of the aMMP-8 test significantly correlate with generalized ChP. The aMMP-8 test may be used by physicians to detect periodontitis in their patients.

  14. Orally administered betaine reduces photodamage caused by UVB irradiation through the regulation of matrix metalloproteinase-9 activity in hairless mice.

    PubMed

    Im, A-Rang; Lee, Hee Jeong; Youn, Ui Joung; Hyun, Jin Won; Chae, Sungwook

    2016-01-01

    Betaine is widely distributed in plants, microorganisms, in several types of food and in medical herbs, including Lycium chinense. The administration of 100 mg betaine/kg body weight/day is an effective strategy for preventing ultraviolet irradiation‑induced skin damage. The present study aimed to determine the preventive effects of betaine on ultraviolet B (UVB) irradiation‑induced skin damage in hairless mice. The mice were divided into three groups: Control (n=5), UVB‑treated vehicle (n=5) and UVB‑treated betaine (n=5) groups. The level of irradiation was progressively increased between 60 mJ/cm2 per exposure at week 1 (one minimal erythematous dose = 60 mJ/cm2) and 90 mJ/cm2 per exposure at week 7. The formation of wrinkles significantly increased following UVB exposure in the UVB‑treated vehicle group. However, treatment with betaine suppressed UVB‑induced wrinkle formation, as determined by the mean length, mean depth, number, epidermal thickness and collagen damage. Furthermore, oral administration of betaine also inhibited the UVB‑induced expression of mitogen‑activated protein kinase kinase (MEK), extracellular signal‑regulated kinase (ERK), and matrix metalloproteinase‑9 (MMP‑9). These findings suggested that betaine inhibits UVB‑induced skin damage by suppressing increased expression of MMP‑9 through the inhibition of MEK and ERK.

  15. Optimal topology and experimental evaluation of PE materials for actively shunted GE polymer matrix fiber composite blades

    NASA Astrophysics Data System (ADS)

    Choi, Benjamin B.; Duffy, Kirsten; Kauffman, Jeffrey L.; Kray, Nicholas

    2012-04-01

    NASA Glenn Research Center (GRC), in collaboration with GE Aviation, has begun the development of a smart adaptive structure system with piezoelectric transducers to improve composite fan blade damping at resonances. Traditional resonant damping approaches may not be realistic for rotating frame applications such as engine blades. The limited space in which the blades reside in the engine makes it impossible to accommodate the circuit size required to implement passive resonant damping. Thus, we have developed a novel digital shunt scheme to replace the conventional electric passive shunt circuits. The digital shunt dissipates strain energy through the load capacitor on a power amplifier. GE designed and fabricated a variety of polymer matrix fiber composite (PMFC) test specimens. We investigated the optimal topology of PE sensors and actuators for each test specimen to discover the best PE transducer location for each target mode. Also a variety of flexible patches, which can conform to the blade surface, have been tested to identify the best performing piezoelectric patch. The active damping control achieved significant performance at target modes. This work has been highlighted by successful spin testing up to 5,000 rpm of subscale GEnx composite blades in GRC's Dynamic Spin Rig.

  16. Readout for intersatellite laser interferometry: Measuring low frequency phase fluctuations of high-frequency signals with microradian precision

    NASA Astrophysics Data System (ADS)

    Gerberding, Oliver; Diekmann, Christian; Kullmann, Joachim; Tröbs, Michael; Bykov, Ioury; Barke, Simon; Brause, Nils Christopher; Esteban Delgado, Juan José; Schwarze, Thomas S.; Reiche, Jens; Danzmann, Karsten; Rasmussen, Torben; Hansen, Torben Vendt; Enggaard, Anders; Pedersen, Søren Møller; Jennrich, Oliver; Suess, Martin; Sodnik, Zoran; Heinzel, Gerhard

    2015-07-01

    Precision phase readout of optical beat note signals is one of the core techniques required for intersatellite laser interferometry. Future space based gravitational wave detectors like eLISA require such a readout over a wide range of MHz frequencies, due to orbit induced Doppler shifts, with a precision in the order of μ rad / √{ Hz } at frequencies between 0.1 mHz and 1 Hz. In this paper, we present phase readout systems, so-called phasemeters, that are able to achieve such precisions and we discuss various means that have been employed to reduce noise in the analogue circuit domain and during digitisation. We also discuss the influence of some non-linear noise sources in the analogue domain of such phasemeters. And finally, we present the performance that was achieved during testing of the elegant breadboard model of the LISA phasemeter, which was developed in the scope of a European Space Agency technology development activity.

  17. Response function of super-resolution readout of an optical disc studied by coupled electromagnetic-thermal simulation

    NASA Astrophysics Data System (ADS)

    Sano, Haruyuki; Shima, Takayuki; Kuwahara, Masashi; Fujita, Yoshiya; Uchiyama, Munehisa; Aono, Yoshiyuki

    2016-09-01

    To fully understand the properties of the readout signal in the super-resolution state, we implemented a multi-physics simulation of the propagation of electromagnetic waves and heat conduction in an optical disc that incorporates an InSb active layer. Response functions were obtained by calculating the light intensity reflected from a single small-pit structure. It was found that a typical response function in the super-resolution state has an asymmetric double-peak structure with high-spatial-frequency components. The complex profile of the response function indicated that the position of protrusions in the readout signal does not exactly correspond to that of the refractive index profile of the pit arrangement. We demonstrated that the measured readout signals also exhibit this particular characteristic and are roughly reproduced by the signals estimated from the response functions.

  18. Response function of super-resolution readout of an optical disc studied by coupled electromagnetic–thermal simulation

    NASA Astrophysics Data System (ADS)

    Sano, Haruyuki; Shima, Takayuki; Kuwahara, Masashi; Fujita, Yoshiya; Uchiyama, Munehisa; Aono, Yoshiyuki

    2016-09-01

    To fully understand the properties of the readout signal in the super-resolution state, we implemented a multi-physics simulation of the propagation of electromagnetic waves and heat conduction in an optical disc that incorporates an InSb active layer. Response functions were obtained by calculating the light intensity reflected from a single small-pit structure. It was found that a typical response function in the super-resolution state has an asymmetric double-peak structure with high-spatial-frequency components. The complex profile of the response function indicated that the position of protrusions in the readout signal does not exactly correspond to that of the refractive index profile of the pit arrangement. We demonstrated that the measured readout signals also exhibit this particular characteristic and are roughly reproduced by the signals estimated from the response functions.

  19. Advanced ACTPol Cryogenic Detector Arrays and Readout

    NASA Astrophysics Data System (ADS)

    Henderson, S. W.; Allison, R.; Austermann, J.; Baildon, T.; Battaglia, N.; Beall, J. A.; Becker, D.; De Bernardis, F.; Bond, J. R.; Calabrese, E.; Choi, S. K.; Coughlin, K. P.; Crowley, K. T.; Datta, R.; Devlin, M. J.; Duff, S. M.; Dunkley, J.; Dünner, R.; van Engelen, A.; Gallardo, P. A.; Grace, E.; Hasselfield, M.; Hills, F.; Hilton, G. C.; Hincks, A. D.; Hloẑek, R.; Ho, S. P.; Hubmayr, J.; Huffenberger, K.; Hughes, J. P.; Irwin, K. D.; Koopman, B. J.; Kosowsky, A. B.; Li, D.; McMahon, J.; Munson, C.; Nati, F.; Newburgh, L.; Niemack, M. D.; Niraula, P.; Page, L. A.; Pappas, C. G.; Salatino, M.; Schillaci, A.; Schmitt, B. L.; Sehgal, N.; Sherwin, B. D.; Sievers, J. L.; Simon, S. M.; Spergel, D. N.; Staggs, S. T.; Stevens, J. R.; Thornton, R.; Van Lanen, J.; Vavagiakis, E. M.; Ward, J. T.; Wollack, E. J.

    2016-08-01

    Advanced ACTPol is a polarization-sensitive upgrade for the 6 m aperture Atacama Cosmology Telescope, adding new frequencies and increasing sensitivity over the previous ACTPol receiver. In 2016, Advanced ACTPol will begin to map approximately half the sky in five frequency bands (28-230 GHz). Its maps of primary and secondary cosmic microwave background anisotropies—imaged in intensity and polarization at few arcminute-scale resolution—will enable precision cosmological constraints and also a wide array of cross-correlation science that probes the expansion history of the universe and the growth of structure via gravitational collapse. To accomplish these scientific goals, the Advanced ACTPol receiver will be a significant upgrade to the ACTPol receiver, including four new multichroic arrays of cryogenic, feedhorn-coupled AlMn transition edge sensor polarimeters (fabricated on 150 mm diameter wafers); a system of continuously rotating meta-material silicon half-wave plates; and a new multiplexing readout architecture which uses superconducting quantum interference devices and time division to achieve a 64-row multiplexing factor. Here we present the status and scientific goals of the Advanced ACTPol instrument, emphasizing the design and implementation of the Advanced ACTPol cryogenic detector arrays.

  20. Conformational readout of RNA by small ligands

    PubMed Central

    Kligun, Efrat; Mandel-Gutfreund, Yael

    2013-01-01

    RNA molecules have highly versatile structures that can fold into myriad conformations, providing many potential pockets for binding small molecules. The increasing number of available RNA structures, in complex with proteins, small ligands and in free form, enables the design of new therapeutically useful RNA-binding ligands. Here we studied RNA ligand complexes from 10 RNA groups extracted from the protein data bank (PDB), including adaptive and non-adaptive complexes. We analyzed the chemical, physical, structural and conformational properties of binding pockets around the ligand. Comparing the properties of ligand-binding pockets to the properties of computed pockets extracted from all available RNA structures and RNA-protein interfaces, revealed that ligand-binding pockets, mainly the adaptive pockets, are characterized by unique properties, specifically enriched in rare conformations of the nucleobase and the sugar pucker. Further, we demonstrate that nucleotides possessing the rare conformations are preferentially involved in direct interactions with the ligand. Overall, based on our comprehensive analysis of RNA-ligand complexes, we suggest that the unique conformations adopted by RNA nucleotides play an important role in RNA recognition by small ligands. We term the recognition of a binding site by a ligand via the unique RNA conformations “RNA conformational readout.” We propose that “conformational readout” is a general way by which RNA binding pockets are recognized and selected from an ensemble of different RNA states. PMID:23618839

  1. Development of the readout controller for KASINICS

    NASA Astrophysics Data System (ADS)

    Cho, Seoung-hyun; Jin, Ho; Nam, Uk-Won; Lee, Sungho; Kong, Kyung-Nam; Yuk, In-Soo; Park, Youngsik; Pak, Soojong; Han, Wonyong; Kim, Sungsoo S.

    2006-06-01

    Korea Astronomy and Space Science Institute (KASI) is developing the KASI Near Infrared Camera System (KASINICS) which will be installed on the 61 cm telescope at the Sobaeksan Optical Astronomy Observatory (SOAO) in Korea. KASINICS is equipped with a ALADDIN III Quadrant (512×512 InSb array, manufactured by Raytheon). For this instrument, we make a new IR array control electronics system. The controller consists of DSP, Bias, Clock, and Video boards which are installed on a VME bus system. The DSP board includes TMS320C6713, FPGA, and 384MB SDRAM. Clock patterns are downloaded from a PC and stored on the FPGA. USB 2.0 is used for the communication with the PC and UART for the serial communication with peripherals. Each of two video boards has 4 video channels. The Bias board provides 16 voltage sources and the Clock board has 15 clock channels. Our goal of readout speed is 10 frames sec -1. We have successfully finished operational tests of the controller using a 256×256 ROIC (CRC744). We are now upgrading the system for the ALADDIN III array. We plan to operate KASINICS by the end of 2006.

  2. Optimal signal processing for continuous qubit readout

    NASA Astrophysics Data System (ADS)

    Ng, Shilin; Tsang, Mankei

    2014-08-01

    The measurement of a quantum two-level system, or a qubit in modern terminology, often involves an electromagnetic field that interacts with the qubit, before the field is measured continuously and the qubit state is inferred from the noisy field measurement. During the measurement, the qubit may undergo spontaneous transitions, further obscuring the initial qubit state from the observer. Taking advantage of some well-known techniques in stochastic detection theory, here we propose a signal processing protocol that can infer the initial qubit state optimally from the measurement in the presence of noise and qubit dynamics. Assuming continuous quantum-nondemolition measurements with Gaussian or Poissonian noise and a classical Markov model for the qubit, we derive analytic solutions to the protocol in some special cases of interest using Itō calculus. Our method is applicable to multihypothesis testing for robust qubit readout and relevant to experiments on qubits in superconducting microwave circuits, trapped ions, nitrogen-vacancy centers in diamond, semiconductor quantum dots, or phosphorus donors in silicon.

  3. Advanced ACTPol Cryogenic Detector Arrays and Readout

    NASA Technical Reports Server (NTRS)

    Henderson, S.W.; Allison, R.; Austermann, J.; Baildon, T.; Battaglia, N.; Beall, J. A.; Becker, D.; De Bernardis, F.; Bond, J. R.; Wollack, E. J.

    2016-01-01

    Advanced ACTPol is a polarization-sensitive upgrade for the 6 m aperture Atacama Cosmology Telescope, adding new frequencies and increasing sensitivity over the previous ACTPol receiver. In 2016, Advanced ACTPol will begin to map approximately half the sky in five frequency bands (28-230 GHz). Its maps of primary and secondary cosmic microwave background anisotropies-imaged in intensity and polarization at few arcminute-scale resolution-will enable precision cosmological constraints and also awide array of cross-correlation science that probes the expansion history of the universe and the growth of structure via gravitational collapse. To accomplish these scientific goals, the AdvancedACTPol receiver will be a significant upgrade to the ACTPol receiver, including four new multichroic arrays of cryogenic, feedhorn-coupled AlMn transition edge sensor polarimeters (fabricated on 150 mm diameter wafers); a system of continuously rotating meta-material silicon half-wave plates; and a new multiplexing readout architecture which uses superconducting quantum interference devices and time division to achieve a 64-row multiplexing factor. Here we present the status and scientific goals of the Advanced ACTPol instrument, emphasizing the design and implementation of the AdvancedACTPol cryogenic detector arrays.

  4. Pesticide-Exposure Matrix

    Cancer.gov

    The "Pesticide-exposure Matrix" was developed to help epidemiologists and other researchers identify the active ingredients to which people were likely exposed when their homes and gardens were treated for pests in past years.

  5. Information Flow in the Readout of a Superconducting Quantum Bit

    NASA Astrophysics Data System (ADS)

    Siddiqi, I.; Vijay, R.; Metcalfe, M.; Boaknin, E.; Rigetti, C.; Frunzio, L.; Shoelkopf, R.; Devoret, M. H.

    2006-03-01

    Quantum computation requires efficient and well controlled coupling between qubits. Superconducting qubits can be strongly coupled using passive electrical circuit elements, but one of the major remaining challenges is to eliminate uncontrolled coupling to parasitic degrees of freedom. I will present experimental results on charge qubits integrated with a novel readout device -- the Josephson bifurcation amplifier (JBA). New experiments using the improved readout fidelity and speed of the JBA quantify parasitic losses and shed light on their mechanism.

  6. FPIX2, the BTeV pixel readout chip

    SciTech Connect

    David C. Christian et al.

    2003-12-10

    A radiation tolerant pixel readout chip, FPIX2, has been developed at Fermilab for use by BTeV. Some of the requirements of the BTeV pixel readout chip are reviewed and contrasted with requirements for similar devices in LHC experiments. A description of the FPIX2 is given, and results of initial tests of its performance are presented, as is a summary of measurements planned for the coming year.

  7. The Philosophy and Feasibility of Dual Readout Calorimetry

    SciTech Connect

    Hauptman, John

    2006-10-27

    I will discuss the general physical ideas behind dual-readout calorimetry, their implementation in DREAM (Dual REAdout Module) with exact separation of scintillation and Cerenkov light, implementation with mixed light in DREAM fibers, anticipated implementation in PbWO4 crystals with applications to the 4th Concept detector and to CMS, use in high energy gamma-ray and cosmic ray astrophysics with Cerenkov and N2 fluorescent light, and implementation in the 4th Concept detector for muon identification.

  8. Transdermal delivery of Diltiazem HCl from matrix film: Effect of penetration enhancers and study of antihypertensive activity in rabbit model

    PubMed Central

    Parhi, Rabinarayan; Suresh, Padilam

    2015-01-01

    The present investigation focused on the development of Diltiazem HCl (DTH) matrix film and its characterization by in-vitro, ex-vivo and in-vivo methods. Films were prepared by solvent casting method by taking different ratios of hydroxypropyl methylcellulose K4M (HPMC K4M) and Eudragit RS100. Various parameters of the films were analyzed such as mechanical property using tensile tester, interaction study by Fourier transform infrared spectroscopy (FTIR) and Thermogravimetric analysis (TGA), in-vitro drug release through cellulose acetate membrane, ex-vivo permeation study using abdominal skin of rat employing Franz diffusion cell, and in-vivo antihypertensive activity using rabbit model. The FTIR studies confirmed the absence of interaction between DTH and selected polymers. Thermal analysis showed the shifting of endothermic peak of DTH in film, indicating the dispersion of DTH in molecular form throughout the film. Incorporation of 1,8-cineole showed highest flux (89.7 μg/cm2/h) of DTH compared to other penetration enhancers such as capsaicin, dimethyl sulfoxide (DMSO), and N-methyl pyrrolidone (NMP). Photomicrographs of histology study on optimized formulation (DF9) illustrated disruption of stratum corneum (SC) supporting the ex-vivo results. The in-vivo antihypertensive activity results demonstrated that formulation DF9 was effective in reducing arterial blood pressure in normotensive rabbits. SEM analysis of films kept for stability study (40 ± 2 °C/75% ± 5%RH for 3 months) revealed the formation of drug crystals which may be due to higher temperature. The findings of the study provide a better alternative dosage form of DTH for the effective treatment of hypertension with enhanced patient compliance. PMID:27222758

  9. Transdermal delivery of Diltiazem HCl from matrix film: Effect of penetration enhancers and study of antihypertensive activity in rabbit model.

    PubMed

    Parhi, Rabinarayan; Suresh, Padilam

    2016-05-01

    The present investigation focused on the development of Diltiazem HCl (DTH) matrix film and its characterization by in-vitro, ex-vivo and in-vivo methods. Films were prepared by solvent casting method by taking different ratios of hydroxypropyl methylcellulose K4M (HPMC K4M) and Eudragit RS100. Various parameters of the films were analyzed such as mechanical property using tensile tester, interaction study by Fourier transform infrared spectroscopy (FTIR) and Thermogravimetric analysis (TGA), in-vitro drug release through cellulose acetate membrane, ex-vivo permeation study using abdominal skin of rat employing Franz diffusion cell, and in-vivo antihypertensive activity using rabbit model. The FTIR studies confirmed the absence of interaction between DTH and selected polymers. Thermal analysis showed the shifting of endothermic peak of DTH in film, indicating the dispersion of DTH in molecular form throughout the film. Incorporation of 1,8-cineole showed highest flux (89.7 μg/cm(2)/h) of DTH compared to other penetration enhancers such as capsaicin, dimethyl sulfoxide (DMSO), and N-methyl pyrrolidone (NMP). Photomicrographs of histology study on optimized formulation (DF9) illustrated disruption of stratum corneum (SC) supporting the ex-vivo results. The in-vivo antihypertensive activity results demonstrated that formulation DF9 was effective in reducing arterial blood pressure in normotensive rabbits. SEM analysis of films kept for stability study (40 ± 2 °C/75% ± 5%RH for 3 months) revealed the formation of drug crystals which may be due to higher temperature. The findings of the study provide a better alternative dosage form of DTH for the effective treatment of hypertension with enhanced patient compliance. PMID:27222758

  10. Increased cyclooxygenase activity impairs apoptosis of inflammatory neutrophils in mice lacking gelatinase B/matrix metalloproteinase-9

    PubMed Central

    Kolaczkowska, Elzbieta; Plytycz, Barbara; Arnold, Bernd; Piccard, Helene; Opdenakker, Ghislain

    2009-01-01

    Matrix metalloproteinase-9 (MMP-9)/gelatinase B plays an important role in neutrophil infiltration during inflammation and cyclooxygenases (COX-1 and COX-2) and their products are important regulators of inflammation. Recently, we reported that a genetic lack of MMP-9 impairs neutrophil infiltration during early zymosan-induced peritonitis but at later stages (> 24 hr) neutrophils persist in the peritoneal cavity. Here we show that this is the result of impaired apoptosis of MMP-9−/−-derived leucocytes. As enhanced COX-1 expression was reported in MMP-9−/− mice, we evaluated the hypothesis that altered COX expression induced the above phenomenon as COX-dependent prostaglandins can act either anti-apoptotically (PGE2) or pro-apoptotically (PGD2). The current data demonstrate that messenger RNA and protein expression of both COX isoforms and their activities are increased in MMP-9−/− mice during late peritonitis. Application of selective COX inhibitors revealed enhanced COX-1-dependent PGE2 production and impaired COX-2-dependent PGD2 synthesis in MMP-9−/− mice. Most importantly, inhibition of COX-1 abolished prolonged neutrophil accumulation in the peritoneal cavity of MMP-9−/− mice and increased apoptosis of inflammatory leucocytes. Similarly, weaker apoptosis of MMP-9−/− bone marrow neutrophils treated in vitro with zymosan was reversed by COX-1 inhibition. In conclusion, enhanced COX-1 expression is responsible for persistent neutrophil presence in the peritoneum of MMP-9−/− mice because of increased synthesis of anti-apoptotic PGE2. In non-transgenic mice, however, inflammatory leucocytes die apoptotically in the late stages of peritonitis as a result of COX-2-dependent PGD2 activity. Overall, we show a dependence of COX expression on the presence of MMP-9. PMID:19175797

  11. Simple Bulk Readout of Digital Nucleic Acid Quantification Assays.

    PubMed

    Morinishi, Leanna S; Blainey, Paul

    2015-01-01

    Digital assays are powerful methods that enable detection of rare cells and counting of individual nucleic acid molecules. However, digital assays are still not routinely applied, due to the cost and specific equipment associated with commercially available methods. Here we present a simplified method for readout of digital droplet assays using a conventional real-time PCR instrument to measure bulk fluorescence of droplet-based digital assays. We characterize the performance of the bulk readout assay using synthetic droplet mixtures and a droplet digital multiple displacement amplification (MDA) assay. Quantitative MDA particularly benefits from a digital reaction format, but our new method applies to any digital assay. For established digital assay protocols such as digital PCR, this method serves to speed up and simplify assay readout. Our bulk readout methodology brings the advantages of partitioned assays without the need for specialized readout instrumentation. The principal limitations of the bulk readout methodology are reduced dynamic range compared with droplet-counting platforms and the need for a standard sample, although the requirements for this standard are less demanding than for a conventional real-time experiment. Quantitative whole genome amplification (WGA) is used to test for contaminants in WGA reactions and is the most sensitive way to detect the presence of DNA fragments with unknown sequences, giving the method great promise in diverse application areas including pharmaceutical quality control and astrobiology. PMID:26436576

  12. Development and commissioning of the HARDROC based readout for the INO-ICAL experiment

    NASA Astrophysics Data System (ADS)

    Kumar, Ashok; Gaur, Ankit; Phogat, Aman; Rafik, Md.; Naimuddin, Md.

    2016-10-01

    Glass based Resistive Plate Chambers (RPCs) are going to be used as an active element in the Iron Calorimeter (ICAL) experiment at the India based Neutrino Observatory (INO), which is being constructed to study atmospheric neutrinos. Though the RPC detector operational parameters are more or less finalized, the readout electronics is being developed using various technologies. The ICAL experiment will consist of about 29,000 RPC detectors of 2 m × 2 m in size with each detector having 64 readout channels both in the X and Y directions. The present study focusses on multi-channel electronics based on SiGe 350 nm technology as an option for the INO-ICAL RPC detectors. The study includes commissioning and usage of frontend application specific integrated circuit (ASIC) HARDROC chip in which 64 channels are handled independently to perform zero suppression. We present first testbench results using the HARDROC chip with the aim to use it finally in the ICAL experiment.

  13. Purcell-enhanced optical spin readout of nitrogen-vacancy centers in diamond

    NASA Astrophysics Data System (ADS)

    Wolf, S. A.; Rosenberg, I.; Rapaport, R.; Bar-Gill, N.

    2015-12-01

    Nitrogen-vacancy (NV) color centers in diamond have emerged as promising quantum solid-state systems, with applications ranging from quantum information processing to magnetic sensing. One of the most useful properties of NVs is the ability to read their ground-state spin projection optically at room temperature. Using theoretical analysis of Purcell-enhanced NV optical coupling, we identify parameters for a significantly enhanced single-to-noise ratio (SNR) of the optical spin-state readout. We then demonstrate that a combined increase in spontaneous emission (through Purcell enhancement) and in optical excitation could significantly increase the readout SNR. Our combined analytical and numerical analysis, which is relevant for various optically active solid-state systems, differentiates between state-mixing processes and provides insights into the optimal light-matter coupling design.

  14. Scintillator high-gain avalanche rushing photoconductor active-matrix flat panel imager: Zero-spatial frequency x-ray imaging properties of the solid-state SHARP sensor structure

    SciTech Connect

    Wronski, M.; Zhao, W.; Tanioka, K.; DeCrescenzo, G.; Rowlands, J. A.

    2012-11-15

    Purpose: The authors are investigating the feasibility of a new type of solid-state x-ray imaging sensor with programmable avalanche gain: scintillator high-gain avalanche rushing photoconductor active matrix flat panel imager (SHARP-AMFPI). The purpose of the present work is to investigate the inherent x-ray detection properties of SHARP and demonstrate its wide dynamic range through programmable gain. Methods: A distributed resistive layer (DRL) was developed to maintain stable avalanche gain operation in a solid-state HARP. The signal and noise properties of the HARP-DRL for optical photon detection were investigated as a function of avalanche gain both theoretically and experimentally, and the results were compared with HARP tube (with electron beam readout) used in previous investigations of zero spatial frequency performance of SHARP. For this new investigation, a solid-state SHARP x-ray image sensor was formed by direct optical coupling of the HARP-DRL with a structured cesium iodide (CsI) scintillator. The x-ray sensitivity of this sensor was measured as a function of avalanche gain and the results were compared with the sensitivity of HARP-DRL measured optically. The dynamic range of HARP-DRL with variable avalanche gain was investigated for the entire exposure range encountered in radiography/fluoroscopy (R/F) applications. Results: The signal from HARP-DRL as a function of electric field showed stable avalanche gain, and the noise associated with the avalanche process agrees well with theory and previous measurements from a HARP tube. This result indicates that when coupled with CsI for x-ray detection, the additional noise associated with avalanche gain in HARP-DRL is negligible. The x-ray sensitivity measurements using the SHARP sensor produced identical avalanche gain dependence on electric field as the optical measurements with HARP-DRL. Adjusting the avalanche multiplication gain in HARP-DRL enabled a very wide dynamic range which encompassed all

  15. Common Readout Unit (CRU) - A new readout architecture for the ALICE experiment

    NASA Astrophysics Data System (ADS)

    Mitra, J.; Khan, S. A.; Mukherjee, S.; Paul, R.

    2016-03-01

    The ALICE experiment at the CERN Large Hadron Collider (LHC) is presently going for a major upgrade in order to fully exploit the scientific potential of the upcoming high luminosity run, scheduled to start in the year 2021. The high interaction rate and the large event size will result in an experimental data flow of about 1 TB/s from the detectors, which need to be processed before sending to the online computing system and data storage. This processing is done in a dedicated Common Readout Unit (CRU), proposed for data aggregation, trigger and timing distribution and control moderation. It act as common interface between sub-detector electronic systems, computing system and trigger processors. The interface links include GBT, TTC-PON and PCIe. GBT (Gigabit transceiver) is used for detector data payload transmission and fixed latency path for trigger distribution between CRU and detector readout electronics. TTC-PON (Timing, Trigger and Control via Passive Optical Network) is employed for time multiplex trigger distribution between CRU and Central Trigger Processor (CTP). PCIe (Peripheral Component Interconnect Express) is the high-speed serial computer expansion bus standard for bulk data transport between CRU boards and processors. In this article, we give an overview of CRU architecture in ALICE, discuss the different interfaces, along with the firmware design and implementation of CRU on the LHCb PCIe40 board.

  16. Coadministration of branched-chain amino acids and lipopolysaccharide causes matrix metalloproteinase activation and blood-brain barrier breakdown.

    PubMed

    Scaini, Giselli; Morais, Meline O S; Galant, Leticia S; Vuolo, Francieli; Dall'Igna, Dhébora M; Pasquali, Matheus A B; Ramos, Vitor M; Gelain, Daniel P; Moreira, Jose Claudio F; Schuck, Patrícia F; Ferreira, Gustavo C; Soriano, Francisco G; Dal-Pizzol, Felipe; Streck, Emilio L

    2014-10-01

    Maple syrup urine disease (MSUD) is an inborn error of metabolism caused by a severe deficiency in the activity of the branched-chain α-keto acid dehydrogenase complex, leading to accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine, and valine. Infections have a significant role in precipitating acute metabolic decompensation in patients with MSUD; however, the mechanisms underlying the neurotoxicity in this disorder are poorly understood. In this study, we subjected rats to the coadministration of lipopolysaccharide (LPS), which is a major component of gram-negative bacteria cell walls, and high concentrations of BCAA (H-BCAA) to determine their effects on the permeability of the blood-brain barrier (BBB) and on the levels of matrix metalloproteinases (MMP-2 and MMP-9). Our results demonstrated that the coadministration of H-BCAA and LPS causes breakdown of the BBB and increases the levels of MMP-2 and MMP-9 in the hippocampus of these rats. On the other hand, examination of the cerebral cortex of the 10- and 30-day-old rats revealed a significant difference in Evan's Blue content after coadministration of H-BCAA and LPS, as MMP-9 levels only increased in the cerebral cortex of the 10-day-old rats. In conclusion, these results suggest that the inflammatory process associated with high levels of BCAA causes BBB breakdown. Thus, we suggest that BBB breakdown is relevant to the perpetuation of brain inflammation and may be related to the brain dysfunction observed in MSUD patients. PMID:24390570

  17. Oestradiol Treatment Counteracts the Effect of Fructose-Rich Diet on Matrix Metalloproteinase 9 Expression and NFκB Activation.

    PubMed

    Bundalo, M; Zivkovic, M; Culafic, T; Stojiljkovic, M; Koricanac, G; Stankovic, A

    2015-01-01

    Fructose-rich diet induces metabolic changes similar to those observed in metabolic syndrome. Among other matrix metalloproteinases, MMP-9 has an important role in adverse cardiac remodelling and might have a role in the development of cardiovascular disorders associated with metabolic syndrome. The changes of MMP-9 expression could be mediated via the NFκB pathway. In this study we investigated the effect of fructose-rich diet on MMP-9 expression in the heart of male and female rats, along with the effect of fructose-rich diet and oestradiol on MMP-9 expression in ovariectomized females. We further assessed the effect of fructose-rich diet and oestradiol on NFκB activation, measured as the level of p65 phosphorylation at Ser 276. The results showed that the diet regime did not affect the heart mass. Higher MMP-9 gene expression was found in cardiac tissue of male rats fed the fructose-rich diet than in females on the same diet regime. In ovariectomized females, fructose-rich diet upregulated MMP-9 protein and mRNA expression in the heart, as well as phosphorylation of the p65 subunit of NFκB at Ser 276. Oestradiol replacement therapy reverted these changes in the heart of ovariectomized females. This study has shown that oestradiol could revert the early molecular changes in MMP-9 expression induced by fructose-rich diet that occurred before cardiac hypertrophy development by decreasing phosphorylation of the NFκB p65 subunit at Ser 276.

  18. Piwil2 modulates the proliferation and metastasis of colon cancer via regulation of matrix metallopeptidase 9 transcriptional activity.

    PubMed

    Li, Dawei; Sun, Xing; Yan, Dongwang; Huang, Jianfeng; Luo, Qiongzhen; Tang, Huamei; Peng, Zhihai

    2012-10-01

    Piwi-like protein 2 (Piwil2) has recently emerged as a putative oncogene which is amplified in several human malignancies. However, the role of Piwil2 in colon cancer remains poorly understood. The aim of this study was to investigate the clinical and pathological significance of Piwil2, and the possible role in the proliferation and metastasis of colon cancer. Primary colon cancer paired with adjacent normal colon tissue and lymph node metastasis (LNM) lesions in 66 patients' tissue microarrays (TMA) were used to determine the expression of Piwil2. Knocked down Piwil2 expression in SW620 and SW480 colon cancer cell lines was performed to evaluate the role of Piwil2 in cell proliferation, invasion, metastasis in vitro and tumorigenicity in vivo. The possible roles of Piwil2 in the regulation of a 2 kb matrix metallopeptidase 9 (MMP9) promoter fragment and on the regulation of apoptotic pathways were evaluated by using a luciferase reporter construct and Western blots, respectively. Significantly higher expression levels of Piwil2 were observed in primary colon cancer tissue and in LNM in comparison with normal colon mucosa. Piwil2 expression significantly correlated with more aggressive clinical and pathological parameters with poorer five-year metastasis-free survival and overall survival. Piwil2 silencing significantly reduced cancer cell proliferation, colony formation ability and increased apoptosis in vitro and inhibited tumor growth in vivo. Piwil2 knockdown also attenuated migration and invasion of colon cancer cells via modulation of MMP9 transcriptional activities. Our results indicate that Piwil2 moderates the proliferation and metastasis potential of colon cancer.

  19. The theoretical study of passive and active optical devices via planewave based transfer (scattering) matrix method and other approaches

    SciTech Connect

    Zhuo, Ye

    2011-01-01

    In this thesis, we theoretically study the electromagnetic wave propagation in several passive and active optical components and devices including 2-D photonic crystals, straight and curved waveguides, organic light emitting diodes (OLEDs), and etc. Several optical designs are also presented like organic photovoltaic (OPV) cells and solar concentrators. The first part of the thesis focuses on theoretical investigation. First, the plane-wave-based transfer (scattering) matrix method (TMM) is briefly described with a short review of photonic crystals and other numerical methods to study them (Chapter 1 and 2). Next TMM, the numerical method itself is investigated in details and developed in advance to deal with more complex optical systems. In chapter 3, TMM is extended in curvilinear coordinates to study curved nanoribbon waveguides. The problem of a curved structure is transformed into an equivalent one of a straight structure with spatially dependent tensors of dielectric constant and magnetic permeability. In chapter 4, a new set of localized basis orbitals are introduced to locally represent electromagnetic field in photonic crystals as alternative to planewave basis. The second part of the thesis focuses on the design of optical devices. First, two examples of TMM applications are given. The first example is the design of metal grating structures as replacements of ITO to enhance the optical absorption in OPV cells (chapter 6). The second one is the design of the same structure as above to enhance the light extraction of OLEDs (chapter 7). Next, two design examples by ray tracing method are given, including applying a microlens array to enhance the light extraction of OLEDs (chapter 5) and an all-angle wide-wavelength design of solar concentrator (chapter 8). In summary, this dissertation has extended TMM which makes it capable of treating complex optical systems. Several optical designs by TMM and ray tracing method are also given as a full complement of this

  20. ASIC Readout Circuit Architecture for Large Geiger Photodiode Arrays

    NASA Technical Reports Server (NTRS)

    Vasile, Stefan; Lipson, Jerold

    2012-01-01

    The objective of this work was to develop a new class of readout integrated circuit (ROIC) arrays to be operated with Geiger avalanche photodiode (GPD) arrays, by integrating multiple functions at the pixel level (smart-pixel or active pixel technology) in 250-nm CMOS (complementary metal oxide semiconductor) processes. In order to pack a maximum of functions within a minimum pixel size, the ROIC array is a full, custom application-specific integrated circuit (ASIC) design using a mixed-signal CMOS process with compact primitive layout cells. The ROIC array was processed to allow assembly in bump-bonding technology with photon-counting infrared detector arrays into 3-D imaging cameras (LADAR). The ROIC architecture was designed to work with either common- anode Si GPD arrays or common-cathode InGaAs GPD arrays. The current ROIC pixel design is hardwired prior to processing one of the two GPD array configurations, and it has the provision to allow soft reconfiguration to either array (to be implemented into the next ROIC array generation). The ROIC pixel architecture implements the Geiger avalanche quenching, bias, reset, and time to digital conversion (TDC) functions in full-digital design, and uses time domain over-sampling (vernier) to allow high temporal resolution at low clock rates, increased data yield, and improved utilization of the laser beam.

  1. Digital frequency domain multiplexing readout electronics for the next generation of millimeter telescopes

    NASA Astrophysics Data System (ADS)

    Bender, Amy N.; Cliche, Jean-François; de Haan, Tijmen; Dobbs, Matt A.; Gilbert, Adam J.; Montgomery, Joshua; Rowlands, Neil; Smecher, Graeme M.; Smith, Ken; Wilson, Andrew

    2014-07-01

    Frequency domain multiplexing (fMux) is an established technique for the readout of transition-edge sensor (TES) bolometers in millimeter-wavelength astrophysical instrumentation. In fMux, the signals from multiple detectors are read out on a single pair of wires reducing the total cryogenic thermal loading as well as the cold component complexity and cost of a system. The current digital fMux system, in use by POLARBEAR, EBEX, and the South Pole Telescope, is limited to a multiplexing factor of 16 by the dynamic range of the Superconducting Quantum Interference Device pre-amplifier and the total system bandwidth. Increased multiplexing is key for the next generation of large format TES cameras, such as SPT-3G and POLARBEAR2, which plan to have on the of order 15,000 detectors. Here, we present the next generation fMux readout, focusing on the warm electronics. In this system, the multiplexing factor increases to 64 channels per module (2 wires) while maintaining low noise levels and detector stability. This is achieved by increasing the system bandwidth, reducing the dynamic range requirements though active feedback, and digital synthesis of voltage biases with a novel polyphase filter algorithm. In addition, a version of the new fMux readout includes features such as low power consumption and radiation-hard components making it viable for future space-based millimeter telescopes such as the LiteBIRD satellite.

  2. 3D reconstruction of nuclear reactions using GEM TPC with planar readout

    SciTech Connect

    Bihałowicz, Jan Stefan

    2015-02-24

    The research program of the Extreme Light Infrastructure – Nuclear Physics (ELI-NP) laboratory under construction in Magurele, Romania facilities the need of developing a gaseous active-target detector providing 3D reconstruction of charged products of nuclear reactions induced by gamma beam. The monoenergetic, high-energy (E{sub γ} > 19 MeV) gamma beam of intensity 10{sup 13}γ/s allows studying nuclear reactions in astrophysics. A Time Projection Chamber with crossed strip readout (eTPC) is proposed as one of the imaging detectors. The special feature of the readout electrode structure is a 2D reconstruction based on the information read out simultaneously from three arrays of strips that form virtual pixels. It is expected to reach similar spatial resolution as for pixel readout at largely reduced cost of electronics. The paper presents the current progress and first results of the small scale prototype TPC which is a one of implementation steps towards eTPC detector proposed in the Technical Design Report of Charged Particles Detection at ELI-NP.

  3. Indirect readout in protein-peptide recognition: a different story from classical biomolecular recognition.

    PubMed

    Yu, Hua; Zhou, Peng; Deng, Maolin; Shang, Zhicai

    2014-07-28

    Protein-peptide interactions are prevalent and play essential roles in many living activities. Peptides recognize their protein partners by direct nonbonded interactions and indirect adjustment of conformations. Although processes of protein-peptide recognition have been comprehensively studied in both sequences and structures recently, flexibility of peptides and the configuration entropy penalty in recognition did not get enough attention. In this study, 20 protein-peptide complexes and their corresponding unbound peptides were investigated by molecular dynamics simulations. Energy analysis revealed that configurational entropy penalty introduced by restriction of the degrees of freedom of peptides in indirect readout process of protein-peptide recognition is significant. Configurational entropy penalty has become the main content of the indirect readout energy in protein-peptide recognition instead of deformation energy which is the main source of the indirect readout energy in classical biomolecular recognition phenomena, such as protein-DNA binding. These results provide us a better understanding of protein-peptide recognition and give us some implications in peptide ligand design.

  4. Readout IC requirement trends based on a simplified parametric seeker model.

    SciTech Connect

    Osborn, Thor D.

    2010-03-01

    Modern space based optical sensors place substantial demands on the focal plane array readout integrated circuit. Active pixel readout designs offer direct access to individual pixel data but require analog to digital conversion at or near each pixel. Thus, circuit designers must create precise, fundamentally analog circuitry within tightly constrained areas on the integrated circuit. Rapidly changing phenomena necessitate tradeoffs between sampling and conversion speed, data precision, and heat generation adjacent the detector array, especially of concern for thermally sensitive space grade infrared detectors. A simplified parametric model is presented that illustrates seeker system performance and analog to digital conversion requirements trends in the visible through mid-wave infrared, for varying sample rate. Notional limiting-case Earth optical backgrounds were generated using MODTRAN4 with a range of cloud extremes and approximate practical albedo limits for typical surface features from a composite of the Mosart and Aster spectral albedo databases. The dynamic range requirements imposed by these background spectra are discussed in the context of optical band selection and readout design impacts.

  5. Correlation between matrix metalloproteinase expression and activation of the focal adhesion kinase signaling pathway in herpes stromal keratitis

    PubMed Central

    CAO, TING; XING, YIQIAO; YANG, YANNING; MEI, HAIFENG

    2014-01-01

    The present study aimed to investigate the correlation between matrix metalloproteinase-2 (MMP-2) expression and activation of the focal adhesion kinase (FAK) signaling pathway in herpes stromal keratitis (HSK). The cornea of 24 BALB/c mice was infected with herpes simplex virus type 1 (HSV-1) to construct a model of HSK. Six additional mice served as negative controls. Immunohistochemical staining was used to detect FAK expression levels. Human corneal epithelial (HCE) cells cultured in vitro were infected with HSV-1 and the expression levels of MMP-2, FAK and phosphorylated-FAK (p-FAK) in HCE cells were detected using reverse transcription-polymerase chain reaction (RT-PCR), western blot analysis and immunohistochemistry at 2, 20 and 40 h following infection. In the HSK rat model, the corneal epithelial cells appeared deranged and the number of neutrophils and FAK-positive cells was significantly increased compared with that of the negative control group (P<0.05). Repeated measures analysis of variance of RT-PCR showed no significant differences in MMP-2 and FAK mRNA expression levels in the infected cells at various time points, and no significant differences between infected cells and the negative control group were observed. There was no interaction between groups and time points. Pairwise comparisons showed that MMP-2 and FAK mRNA expression levels were significantly increased in virus-infected cells compared with those of the control group. Over time, MMP-2 and FAK mRNA expression levels did not differ significantly in virus-infected cells or in control cells. Western blot analysis indicated no significant differences in p-FAK, FAK and MMP-2 expression levels between the infected and control cells at 2 h (P>0.05). Infected cells showed a significant increase in MMP-2 and p-FAK expression levels than that of the control cells at 20 and 40 h (P<0.05). p-FAK, FAK and MMP-2 expression levels in virus-infected cells at 2 h differed significantly from those at 20

  6. Matrix superpotentials

    NASA Astrophysics Data System (ADS)

    Nikitin, Anatoly G.; Karadzhov, Yuri

    2011-07-01

    We present a collection of matrix-valued shape invariant potentials which give rise to new exactly solvable problems of SUSY quantum mechanics. It includes all irreducible matrix superpotentials of the generic form W=kQ+\\frac{1}{k} R+P, where k is a variable parameter, Q is the unit matrix multiplied by a real-valued function of independent variable x, and P and R are the Hermitian matrices depending on x. In particular, we recover the Pron'ko-Stroganov 'matrix Coulomb potential' and all known scalar shape invariant potentials of SUSY quantum mechanics. In addition, five new shape invariant potentials are presented. Three of them admit a dual shape invariance, i.e. the related Hamiltonians can be factorized using two non-equivalent superpotentials. We find discrete spectrum and eigenvectors for the corresponding Schrödinger equations and prove that these eigenvectors are normalizable.

  7. Dedicated multichannel readout ASIC coupled with single crystal diamond for dosimeter application

    NASA Astrophysics Data System (ADS)

    Fabbri, A.; Falco, M. D.; De Notaristefani, F.; Galasso, M.; Marinelli, M.; Orsolini Cencelli, V.; Tortora, L.; Verona, C.; Verona Rinati, G.

    2013-02-01

    This paper reports on the tests of a low-noise, multi-channel readout integrated circuit used as a readout electronic front-end for a diamond multi-pixel dosimeter. The system is developed for dose distribution measurement in radiotherapy applications. The first 10-channel prototype chip was designed and fabricated in a 0.18 um CMOS process. Every channel includes a charge integrator with a 10 pF capacitor and a double slope A/D converter. The diamond multi-pixel detector, based on CVD synthetic single crystal diamond Schottky diodes, is made by a 3 × 3 sensor matrix. The overall device has been tested under irradiation with 6 MeV radio therapeutic photon beams at the Policlinico ``Tor Vergata'' (PTV) hospital. Measurements show a 20 fA RMS leakage current from the front-end input stage and a negligible dark current from the diamond detector, a stable temporal response and a good linear behaviour as a function of both dose and dose rate. These characteristics were common to each tested channel.

  8. Matrix adhesion and Ras transformation both activate a phosphoinositide 3-OH kinase and protein kinase B/Akt cellular survival pathway.

    PubMed Central

    Khwaja, A; Rodriguez-Viciana, P; Wennström, S; Warne, P H; Downward, J

    1997-01-01

    Upon detachment from the extracellular matrix, epithelial cells enter into programmed cell death, a phenomenon known as anoikis, ensuring that they are unable to survive in an inappropriate location. Activated ras oncogenes protect cells from this form of apoptosis. The nature of the survival signals activated by integrin engagement and usurped by oncogenic Ras are unknown: here we show that in both cases phosphoinositide 3-OH kinase (PI 3-kinase), but not Raf, mediates this protection, acting through protein kinase B/Akt (PKB/Akt). Constitutively activated PI 3-kinase or PKB/Akt block anoikis, while inhibition of PI 3-kinase abrogates protection by Ras, but not PKB/Akt. Inhibition of either PI 3-kinase or PKB/Akt induces apoptosis in adherent epithelial cells. Attachment of cells to matrix leads to rapid elevation of the levels of PI 3-kinase lipid products and PKB/Akt activity, both of which remain high in Ras-transformed cells even in suspension. PI 3-kinase acting through PKB/Akt is therefore implicated as a key mediator of the aberrant survival of Ras-transformed epithelial cells in the absence of attachment, and mediates matrix-induced survival of normal epithelial cells. PMID:9184223

  9. Novel concept of TDI readout circuit for LWIR detector

    NASA Astrophysics Data System (ADS)

    Kim, Byunghyuck; Yoon, Nanyoung; Lee, Hee Chul; Kim, Choong-Ki

    2000-07-01

    Noise property is the prime consideration in readout circuit design. The output noise caused by the photon noise, which dominates total noise in BLIP detectors, is limited by the integration time that an element looks at a specific point in the scene. Large integration time leads to a low noise performance. Time-delay integration (TDI) is used to effectively increase the integration time and reduce the photon noise. However, it increases the number of dead pixels and requires large integration capacitors and low noise output stage of the readout circuit. In this paper, to solve these problems, we propose a new concept of readout circuit, which performs background suppression, cell-to-cell background current non-uniformity compensation, and dead pixel correction using memory, ADC, DAC, and current copier cell. In simulation results, comparing with the conventional TDI readout circuit, the integration capacitor size can be reduced to 1/5 and trans-impedance gain can be increased by five times. Therefore, the new TDI readout circuit does not require large area and low noise output stage. And the error of skimming current is less than 2%, and the fixed pattern noise induced by cell-to-cell background current variation is reduced to less than 1%.

  10. FASTBUS Readout Controller card for high speed data acquisition

    SciTech Connect

    Zimmermann, S. Rio Grande do Sul Univ., Porto Alegre, RS . Dept. of Electrical Engineering); Areti, V.H.; Foster, G.W.; Joshi, U.; Treptow, K. )

    1991-10-01

    This article describes a FASTBUS Readout Controller (FRC) for high speed data acquisition in FASTBUS based systems. The controller has two main interfaces: to FASTBUS and to a Readout Port. The FASTBUS interface performs FASTBUS master and slave operations at a maximum transfer rate exceeding 40 MBytes/s. The Readout Port can be adapted for a variety of protocols. Currently, it will be interfaced to a VME bus based processor with a VSB port. The on-board LR33000 embedded processor controls the readout, executing a list of operations download into its memory. It scans the FASTBUS modules and stores the data in a triple port DRAM (TPDRAM), through one of the Serial Access Memory (SAM) ports of the (TPDRAM). Later, it transfers this data to the readout port using the other SAM. The FRC also supports serial communication via RS232 and Ethernet interfaces. This device is intended for use in the data acquisition system at the Collider Detector at Fermilab. 5 refs., 3 figs.

  11. Hyper Suprime-Cam: development of the CCD readout electronics

    NASA Astrophysics Data System (ADS)

    Nakaya, Hidehiko; Uchida, Tomohisa; Miyatake, Hironao; Fujimori, Hiroki; Mineo, Sogo; Aihara, Hiroaki; Furusawa, Hisanori; Kamata, Yukiko; Karoji, Hiroshi; Kawanomoto, Satoshi; Komiyama, Yutaka; Miyazaki, Satoshi; Morokuma, Tomoki; Obuchi, Yoshiyuki; Okura, Yuki; Tanaka, Manobu; Tanaka, Yoko; Uraguchi, Fumihiro; Utsumi, Yosuke

    2010-07-01

    Hyper Suprime-Cam (HSC) employs 116 of 2k×4k CCDs with 464 signal outputs in total. The image size exceeds 2 GBytes, and the data can be readout every 10 seconds which results in the data rate of 210 Mbytes / sec. The data is digitized to 16-bit. The readout noise of the electronics at the readout time of 20 seconds is ~0.9 ADU, and the one with CCD is ~1.5 ADU which corresponds to ~4.5 e. The linearity error fits within +/- 0.5 % up to 150,000 e. The CCD readout electronics for HSC was newly developed based on the electronics for Suprime-Cam. The frontend electronics (FEE) is placed in the vacuum dewar, and the backend electronics (BEE) is mounted on the outside of the dewar on the prime focus unit. The FEE boards were designed to minimize the outgas and to maximize the heat transfer efficiency to keep the vacuum of the dewar. The BEE boards were designed to be simple and small as long as to achieve the readout time within 10 seconds. The production of the system has been finished, and the full set of the boards are being tested with several CCDs installed in the HSC dewar. We will show the system design, performance, and the current status of the development.

  12. [Membrane type 1 matrix metalloproteinase (MT1-MMP) and the regulators of its activity as invasive factors in squamous cell cervical carcinomas].

    PubMed

    Timoshenko, O S; Gureeva, T A; Kugaevskaia, E V; Solov'eva, N I

    2014-01-01

    Membrane type 1 matrix metalloproteinase (MT1MMP) is one of matrix metalloproteinases (MMP), which play а key role in tumor invasion and metastasis. The aim of this study was to elucidate the peculiarities of expression of MT1MMP and endogenous regulators of its activity: the activator - furin and the inhibitor - TIMP-2, as invasive factors of squamous cell cervical carcinomas (SCC). The study was carried out using 11 specimens of SCC and 11 specimens of morphologically normal tissue adjacent to the tumor. It was shown that the increase of MT1-MMP and furin expression and low of TIMP-2 expression makes the main contribution to the destructive (invasive) potential of SCC. Moreover, substantial expression of MT1-MMP was registered in the specimens of morphologically normal adjoining to tumor tissue. This expression was found to make an additional contribution to the destructive potential of the cervical tumor.

  13. Nile red synchronous scan fluorescence spectroscopy to follow matrix modification in sol-gel derived media and its effect on the peroxidase activity of cytochrome c.

    PubMed

    Rei, Ana; Ferreira, M Isabel C; Hungerford, Graham

    2008-11-01

    The highly solvatochromic dye Nile red is used in conjunction with synchronous scan fluorescence spectroscopy to elucidate changes in the internal environment of cytochrome c, upon incorporation into differently modified sol-gel derived media. Nile red was first studied in a variety of solvents in order to quantify changes in polarity. Matrix modifications involved the addition of several silanes, intended to interact with any unreacted hydroxyl entities left from the matrix forming reaction, while polymers were used to help reduce shrinkage and modify the internal pore environment. Slight unfolding of the protein was observed on incorporation into the sol-gel derived media. During the aging process further changes were monitored by using difference synchronous scan fluorescence spectra and complementary measurements of catalytic activity, expressed as the initial velocity. Combining Nile red synchronous scan fluorescence with cytochrome c activity data lead to a method to elucidate effects linked to protein conformation and those related to the sol-gel derived host.

  14. Gafchromic EBT3 film dosimetry in electron beams - energy dependence and improved film read-out.

    PubMed

    Sipilä, Petri; Ojala, Jarkko; Kaijaluoto, Sampsa; Jokelainen, Ilkka; Kosunen, Antti

    2016-01-01

    For megavoltage photon radiation, the fundamental dosimetry characteristics of Gafchromic EBT3 film were determined in 60Co gamma ray beam with addition of experimental and Monte Carlo (MC)-simulated energy dependence of the film for 6 MV photon beam and 6 MeV, 9 MeV, 12 MeV, and 16 MeV electron beams in water phantom. For the film read-out, two phase correction of scanner sensitivity was applied: a matrix correction for scanning area and dose-dependent correction by iterative procedure. With these corrections, the uniformity of response can be improved to be within ± 50 pixel values (PVs). To improve the read-out accuracy, a procedure with flipped film orientations was established. With the method, scanner uniformity can be improved further and dust particles, scratches and/or dirt on scan-ner glass can be detected and eliminated. Responses from red and green channels were averaged for read-out, which decreased the effect of noise present in values from separate channels. Since the signal level with the blue channel is considerably lower than with other channels, the signal variation due to different perturbation effects increases the noise level so that the blue channel is not recommended to be used for dose determination. However, the blue channel can be used for the detection of emulsion thickness variations for film quality evaluations with unexposed films. With electron beams ranging from 6 MeV to 16 MeV and at reference measurement conditions in water, the energy dependence of the EBT3 film is uniform within 0.5%, with uncertainties close to 1.6% (k = 2). Including 6 MV photon beam and the electron beams mentioned, the energy dependence is within 1.1%. No notable differences were found between the experimental and MC-simulated responses, indicating negligible change in intrinsic energy dependence of the EBT3 film for 6 MV photon beam and 6 MeV-16 MeV electron beams. Based on the dosimetric characteristics of the EBT3 film, the read-out procedure established

  15. 18k Channels single photon counting readout circuit for hybrid pixel detector

    NASA Astrophysics Data System (ADS)

    Maj, P.; Grybos, P.; Szczygiel, R.; Zoladz, M.; Sakumura, T.; Tsuji, Y.

    2013-01-01

    We have performed measurements of an integrated circuit named PXD18k designed for hybrid pixel semiconductor detectors used in X-ray imaging applications. The PXD18k integrated circuit, fabricated in CMOS 180 nm technology, has dimensions of 9.64 mm×20 mm and contains approximately 26 million transistors. The core of the IC is a matrix of 96×192 pixels with 100 μm×100 μm pixel size. Each pixel works in a single photon counting mode. A single pixel contains two charge sensitive amplifiers with Krummenacher feedback scheme, two shapers, two discriminators (with independent thresholds A and B) and two 16-bit ripple counters. The data are read out via eight low voltage differential signaling (LVDS) outputs with 100 Mbps rate. The power consumption is dominated by analog blocks and it is about 23 μW/pixel. The effective peaking time at the discriminator input is 30 ns and is mainly determined by the time constants of the charge sensitive amplifier (CSA). The gain is equal to 42.5 μV/e- and the equivalent noise charge is 168 e- rms (with bump-bonded silicon pixel detector). Thanks to the use of trim DACs in each pixel, the effective threshold spread at the discriminator input is only 1.79 mV. The dead time of the front end electronics for a standard setting is 172 ns (paralyzable model). In the standard readout mode (when the data collection time is separated from the time necessary to readout data from the chip) the PXD18k IC works with two energy thresholds per pixel. The PXD18k can also be operated in the continuous readout mode (with a zero dead time) where one can select the number of bits readout from each pixel to optimize the PXD18k frame rate. For example, for reading out 16 bits/pixel the frame rate is 2.7 kHz and for 4 bits/pixel it rises to 7.1 kHz.

  16. Capillary-induced Homogenization of Matrix in Paper: A Powerful Approach for the Quantification of Active Pharmaceutical Ingredients Using Mass Spectrometry Imaging

    NASA Astrophysics Data System (ADS)

    de Menezes, Maico; de Oliveira, Diogo Noin; Catharino, Rodrigo Ramos

    2016-07-01

    Herein we present a novel approach for the quantification of active pharmaceutical ingredients (APIs) using mass spectrometry imaging. This strategy uses a filter paper previously “eluted” with a MALDI matrix solution as a support for analyte application. Samples are submitted to mass spectrometry imaging (MSI) and quantification through characteristic fingerprints is ultimately performed. Results for the content of rosuvastatin from a known formulation are comparable to those obtained with a validated HPLC method.

  17. Capillary-induced Homogenization of Matrix in Paper: A Powerful Approach for the Quantification of Active Pharmaceutical Ingredients Using Mass Spectrometry Imaging

    PubMed Central

    de Menezes, Maico; de Oliveira, Diogo Noin; Catharino, Rodrigo Ramos

    2016-01-01

    Herein we present a novel approach for the quantification of active pharmaceutical ingredients (APIs) using mass spectrometry imaging. This strategy uses a filter paper previously “eluted” with a MALDI matrix solution as a support for analyte application. Samples are submitted to mass spectrometry imaging (MSI) and quantification through characteristic fingerprints is ultimately performed. Results for the content of rosuvastatin from a known formulation are comparable to those obtained with a validated HPLC method. PMID:27439589

  18. The Extracellular Protease Matrix Metalloproteinase-9 Is Activated by Inhibitory Avoidance Learning and Required for Long-Term Memory

    ERIC Educational Resources Information Center

    Nagy, Vanja; Bozdagi, Ozlem; Huntley, George W.

    2007-01-01

    Matrix metalloproteinases (MMPs) are a family of extracellularly acting proteolytic enzymes with well-recognized roles in plasticity and remodeling of synaptic circuits during brain development and following brain injury. However, it is now becoming increasingly apparent that MMPs also function in normal, nonpathological synaptic plasticity of the…

  19. The NA62 Liquid Krypton calorimeter readout architecture

    NASA Astrophysics Data System (ADS)

    Ceccucci, A.; Fantechi, R.; Farthouat, P.; Ryjov, V.; De Simone, N.; Venditti, S.

    2016-01-01

    The NA62 experiment [1] at the CERN SPS (Super Proton Synchrotron) accelerator studies the ultra-rare decays of charged kaons. The high-resolution Liquid Krypton (LKr) electromagnetic calorimeter of the former NA48 experiment [2] is a key component of the experiment photon-veto system. The new LKr readout system comprises 14,000 14-bit ADC acquisition channels, 432× 1 Gbit Ethernet data request and readout links routed by 28× 10 Gbit network switches to the experiment computer farm, and timing, trigger and control (TTC) distribution system. This paper presents the architecture of the LKr readout and TTC systems, the overall performance and the first successfully collected experiment physics data.

  20. A readout for large arrays of microwave kinetic inductance detectors.

    PubMed

    McHugh, Sean; Mazin, Benjamin A; Serfass, Bruno; Meeker, Seth; O'Brien, Kieran; Duan, Ran; Raffanti, Rick; Werthimer, Dan

    2012-04-01

    Microwave kinetic inductance detectors (MKIDs) are superconducting detectors capable of counting single photons and measuring their energy in the UV, optical, and near-IR. MKIDs feature intrinsic frequency domain multiplexing (FDM) at microwave frequencies, allowing the construction and readout of large arrays. Due to the microwave FDM, MKIDs do not require the complex cryogenic multiplexing electronics used for similar detectors, such as transition edge sensors, but instead transfer this complexity to room temperature electronics where they present a formidable signal processing challenge. In this paper, we describe the first successful effort to build a readout for a photon counting optical/near-IR astronomical instrument, the ARray Camera for Optical to Near-infrared Spectrophotometry. This readout is based on open source hardware developed by the Collaboration for Astronomy Signal Processing and Electronics Research. Designed principally for radio telescope backends, it is flexible enough to be used for a variety of signal processing applications.

  1. READOUT SYSTEM FOR ARRAYS OF FRISCH-RING CDZNTE DETECTORS.

    SciTech Connect

    CUI, Y.; BOLOTNIKOV, A.E.; CAMARDA, G.S.; DE GERONIMO, G.; O'CONNOR, P.; JAMES, R.B.; KARGAR, A.; HARRISON, M.J.; MCGREGOR, D.S.

    2006-10-29

    Frisch-ring CdZnTe detectors have demonstrated good energy resolution for identifying isotopes, <1% FWHM at 662 keV, and good efficiency for detecting gamma rays. We will fabricate and test at Brookhaven National Laboratory an integrated module of a 64-element array of 6 x 6 x 12 mm{sup 3} Frisch-ring detectors, coupled with a readout electronics system. It supports 64 readout channels, and includes front-end electronics, signal processing circuit, USB interface and high-voltage power supply. The data-acquisition software is used to process the data stream, which includes amplitude and timing information for each detected event. This paper describes the design and assembly of the detector modules, readout electronics, and a conceptual prototype system. Some test results are also reported.

  2. Quantum Algorithmic Readout in Multi-Ion Clocks.

    PubMed

    Schulte, M; Lörch, N; Leroux, I D; Schmidt, P O; Hammerer, K

    2016-01-01

    Optical clocks based on ensembles of trapped ions promise record frequency accuracy with good short-term stability. Most suitable ion species lack closed transitions, so the clock signal must be read out indirectly by transferring the quantum state of the clock ions to cotrapped logic ions of a different species. Existing methods of quantum logic readout require a linear overhead in either time or the number of logic ions. Here we describe a quantum algorithmic readout whose overhead scales logarithmically with the number of clock ions in both of these respects. The scheme allows a quantum nondemolition readout of the number of excited clock ions using a single multispecies gate operation which can also be used in other areas of ion trap technology such as quantum information processing, quantum simulations, metrology, and precision spectroscopy. PMID:26799016

  3. A compact light readout system for longitudinally segmented shashlik calorimeters

    NASA Astrophysics Data System (ADS)

    Berra, A.; Brizzolari, C.; Cecchini, S.; Cindolo, F.; Jollet, C.; Longhin, A.; Ludovici, L.; Mandrioli, G.; Mauri, N.; Meregaglia, A.; Paoloni, A.; Pasqualini, L.; Patrizii, L.; Pozzato, M.; Pupilli, F.; Prest, M.; Sirri, G.; Terranova, F.; Vallazza, E.; Votano, L.

    2016-09-01

    The longitudinal segmentation of shashlik calorimeters is challenged by dead zones and non-uniformities introduced by the light collection and readout system. This limitation can be overcome by direct fiber-photosensor coupling, avoiding routing and bundling of the wavelength shifter fibers and embedding ultra-compact photosensors (SiPMs) in the bulk of the calorimeter. We present the first experimental test of this readout scheme performed at the CERN PS-T9 beamline in 2015 with negative particles in the 1-5 GeV energy range. In this paper, we demonstrate that the scheme does not compromise the energy resolution and linearity compared with standard light collection and readout systems. In addition, we study the performance of the calorimeter for partially contained charged hadrons to assess the e / π separation capability and the response of the photosensors to direct ionization.

  4. Looking at Earth from space: Direct readout from environmental satellites

    NASA Technical Reports Server (NTRS)

    1994-01-01

    Direct readout is the capability to acquire information directly from meteorological satellites. Data can be acquired from NASA-developed, National Oceanic and Atmospheric Administration (NOAA)-operated satellites, as well as from other nations' meteorological satellites. By setting up a personal computer-based ground (Earth) station to receive satellite signals, direct readout may be obtained. The electronic satellite signals are displayed as images on the computer screen. The images can display gradients of the Earth's topography and temperature, cloud formations, the flow and direction of winds and water currents, the formation of hurricanes, the occurrence of an eclipse, and a view of Earth's geography. Both visible and infrared images can be obtained. This booklet introduces the satellite systems, ground station configuration, and computer requirements involved in direct readout. Also included are lists of associated resources and vendors.

  5. A Triggerless readout system for the bar PANDA electromagnetic calorimeter

    NASA Astrophysics Data System (ADS)

    Tiemens, M.; PANDA Collaboration

    2015-02-01

    One of the physics goals of the future bar PANDA experiment at FAIR is to research newly discovered exotic states. Because the detector response created by these particles is very similar to the background channels, a new type of data readout had to be developed, called "triggerless" readout. In this concept, each detector subsystem preprocesses the signal, so that in a later stage, high-level phyiscs constraints can be applied to select events of interest. A dedicated clock source using a protocol called SODANET over optical fibers ensures proper synchronisation between the components. For this new type of readout, a new way of simulating the detector response also needed to be developed, taking into account the effects of pile-up caused by the 20 MHz interaction rate.

  6. Upgrade of the D0 luminosity monitor readout system

    SciTech Connect

    Anderson, John; Bridges, Lloyd; Casey, Brendan; Enari, Yuji; Green, Johnny; Johnson, Marvin; Kwarciany, Rick; Miao, Chyi-Chiang; Partridge, Richard; Yoo, Hwi Dong; Wang, Jigang; /Brown U. /Fermilab

    2006-12-01

    We describe upgrades to the readout system for the D0 Luminosity Monitor. The D0 Luminosity Monitor consists of plastic scintillation detectors with fine-mesh photomultiplier readout that cover the pseudorapidity range 2.7 < |{eta}| < 4.4. The detector is designed to provide a precise measurement of the rate for non-diffractive inelastic collisions that is used to calculate the TeVatron luminosity at D0. The new readout system is based on custom VME electronics that make precise time-of-flight and charge measurements for each luminosity counter. These measurements are used to identify beam crossings with non-diffractive interactions by requiring in-time hits in both the forward and backward luminosity counters. We have also significantly increased signal/noise for the photomultiplier signals by developing a new front-end preamplifier and improving the grounding scheme.

  7. Sub-10ps monolithic and low-power photodetector readout

    SciTech Connect

    Varner, Gary S.; Ruckman, Larry L.

    2009-02-20

    Recent advances in photon detectors have resulted in high-density imaging arrays that offer many performance and cost advantages. In particular, the excellent transit time spread of certain devices show promise to provide tangible benefits in applications such as Positron Emission Tomography (PET). Meanwhile, high-density, high-performance readout techniques have not kept on pace for exploiting these developments. Photodetector readout for next generation high event rate particle identification and time-resolved PET requires a highly-integrated, low-power, and cost-effective readout technique. We propose fast waveform sampling as a method that meets these criteria and demonstrate that sub-10ps resolution can be obtained for an existing device.

  8. Ultralow Magnetic Fields and Gravity Probe B Gyroscope Readout

    NASA Astrophysics Data System (ADS)

    Mester, J. C.; Lockhart, J. M.; Muhlfelder, B.; Murray, D. O.; Taber, M. A.

    We describe the generation of an ultralow magnetic field of < 10-11Tesla in the flight dewar of the Gravity Probe B Relativity Mission. The field was achieved using expanded-superconducting-shield techniques and is maintained with the aid of a magnetic materials control program. A high performance magnetic shield system is required for the proper function of gyroscope readout. The readout system employs a dc SQUID to measure the London moment generated by the superconducting gyro rotor in order to resolve sub-milliarcsecond changes in the gyro spin direction. In addition to a low residual dc magnetic field, attenuation of external field variation is required to be 1012 at the gyro positions. We discuss the measurement of the dc magnetic field and ac attenuation factor and the performance of the readout system

  9. A readout for large arrays of microwave kinetic inductance detectors.

    PubMed

    McHugh, Sean; Mazin, Benjamin A; Serfass, Bruno; Meeker, Seth; O'Brien, Kieran; Duan, Ran; Raffanti, Rick; Werthimer, Dan

    2012-04-01

    Microwave kinetic inductance detectors (MKIDs) are superconducting detectors capable of counting single photons and measuring their energy in the UV, optical, and near-IR. MKIDs feature intrinsic frequency domain multiplexing (FDM) at microwave frequencies, allowing the construction and readout of large arrays. Due to the microwave FDM, MKIDs do not require the complex cryogenic multiplexing electronics used for similar detectors, such as transition edge sensors, but instead transfer this complexity to room temperature electronics where they present a formidable signal processing challenge. In this paper, we describe the first successful effort to build a readout for a photon counting optical/near-IR astronomical instrument, the ARray Camera for Optical to Near-infrared Spectrophotometry. This readout is based on open source hardware developed by the Collaboration for Astronomy Signal Processing and Electronics Research. Designed principally for radio telescope backends, it is flexible enough to be used for a variety of signal processing applications. PMID:22559560

  10. MT1-MMP promotes cell growth and ERK activation through c-Src and paxillin in three-dimensional collagen matrix

    SciTech Connect

    Takino, Takahisa; Tsuge, Hisashi; Ozawa, Terumasa; Sato, Hiroshi

    2010-06-11

    Membrane-type 1 matrix metalloproteinase (MT1-MMP) is essential for tumor invasion and growth. We show here that MT1-MMP induces extracellular signal-regulated kinase (ERK) activation in cancer cells cultured in collagen gel, which is indispensable for their proliferation. Inhibition of MT1-MMP by MMP inhibitor or small interfering RNA suppressed activation of focal adhesion kinase (FAK) and ERK in MT1-MMP-expressing cancer cells, which resulted in up-regulation of p21{sup WAF1} and suppression of cell growth in collagen gel. Cell proliferation was also abrogated by the inhibitor against ERK pathway without affecting FAK phosphorylation. MT1-MMP and integrin {alpha}{sub v}{beta}{sub 3} were shown to be involved in c-Src activation, which induced FAK and ERK activation in collagen gel. These MT1-MMP-mediated signal transductions were paxillin dependent, as knockdown of paxillin reduced cell growth and ERK activation, and co-expression of MT1-MMP with paxillin induced ERK activation. The results suggest that MT1-MMP contributes to proliferation of cancer cells in the extracellular matrix by activating ERK through c-Src and paxillin.

  11. Performance of Pixel-Readout Micro-Pixel Chamber with Analog-Readout System Used as X-ray Polarimeter

    NASA Astrophysics Data System (ADS)

    Katagiri, Hideaki; Ono, Kenichi; Uchiyama, Hideki; Tsuru, Takeshi Go; Matsumoto, Hironori; Hyodo, Yoshiaki; Kubo, Hidetoshi; Miuchi, Kentaro; Tanimori, Toru

    2007-12-01

    We developed an analog-readout system for a pixel-readout micro-pixel chamber (μ-PIC) to be used as an astronomical X-ray polarimeter, and demonstrated that the sensitivity of the new system reached up to that predicted by a simulation. A pixel-readout μ-PIC is a micro-pattern gaseous detector with a fine position resolution and good stability at sufficient gain operation, and is suited for astronomical X-ray polarimetry. However, as shown by Katagiri et al. (2007), the sensitivity to X-ray polarization was found to be statistically lower by a significant amount than that expected from the simulation of Ueno et al. [Nucl. Instrum. Methods Phys. Res., Sect. A 525 (2004) 28] because of the readout system and background produced by the scattering of the X-ray beam in air. We therefore developed a new readout system and carried out a beam test with aluminum tubes that reduced the background. As a result, we demonstrated that for collimated beams, the modulation factors, which are indicators of the sensitivity to X-ray polarization, were 0.24± 0.08 at 8 keV and 0.18± 0.07 at 15 keV in a neon-based gas mixture, and 0.18± 0.04 at 15 keV in an argon-based mixture. These values are consistent with those predicted by the simulation within errors.

  12. A Cannabinoid Receptor 2 Agonist Prevents Thrombin-Induced Blood-Brain Barrier Damage via the Inhibition of Microglial Activation and Matrix Metalloproteinase Expression in Rats.

    PubMed

    Li, Lin; Tao, Yihao; Tang, Jun; Chen, Qianwei; Yang, Yang; Feng, Zhou; Chen, Yujie; Yang, Liming; Yang, Yunfeng; Zhu, Gang; Feng, Hua; Chen, Zhi

    2015-12-01

    Thrombin mediates the life-threatening cerebral edema and blood-brain barrier (BBB) damage that occurs after intracerebral hemorrhage (ICH). We previously found that the selective cannabinoid receptor 2 (CB2R) agonist JWH-133 reduced brain edema and neurological deficits following germinal matrix hemorrhage (GMH). We explored whether CB2R stimulation ameliorated thrombin-induced brain edema and BBB permeability as well as the possible molecular mechanism involved. A total of 144 Sprague-Dawley (S-D) rats received a thrombin (20 U) injection in the right basal ganglia. JWH-133 (1.5 mg/kg) or SR-144528 (3.0 mg/kg) and vehicle were intraperitoneally (i.p.) injected 1 h after surgery. Brain water content measurement, Evans blue (EB) extravasation, Western blot, and immunofluorescence were used to study the effects of a CB2R agonist 24 h after surgery. The results demonstrated that JWH-133 administration significantly decreased thrombin-induced brain edema and reduced the number of Iba-1-positive microglia. JWH-133 also decreased the number of P44/P42(+)/Iba-1(+) microglia, lowered Evans blue extravasation, and inhibited the elevated matrix metallopeptidase (MMP)-9 and matrix metallopeptidase (MMP)-12 activities. However, a selective CB2R antagonist (SR-144528) reversed these effects. We demonstrated that CB2R stimulation reduced thrombin-induced brain edema and alleviated BBB damage. We also found that matrix metalloproteinase suppression may be partially involved in these processes. PMID:26376816

  13. Temperature compensation method using readout signals of ring laser gyroscope.

    PubMed

    Li, Geng; Wang, Fei; Xiao, Guangzong; Wei, Guo; Zhang, Pengfei; Long, Xingwu

    2015-05-18

    Traditional compensation methods using temperature-related parameters have little effect when the ring laser gyroscope (RLG) bias changes rapidly. To solve this problem, a novel RLG bias temperature compensation method using readout signals is proposed in this paper. Combined with the least squares support vector machine (LS-SVM) algorithm, the novel method can improve the precision of the RLG bias. Experiments show that by utilizing the readout signals in the LS-SVM model, the RLG bias stability can be significantly raised compared to the original data. The novel method proposed in this paper is shown to be feasible, even when the RLG bias changes rapidly.

  14. Common read-out receiver card for ALICE Run2

    NASA Astrophysics Data System (ADS)

    Engel, H.; Kebschull, U.

    2013-12-01

    ALICE at CERN LHC uses custom FPGA-based computer plug-in cards as interface between the optical detector read-out link and the PC clusters of Data Acquisition (DAQ) and High-Level Trigger (HLT). The cards used at DAQ and HLT during Run1 have been developed as independent projects and are now facing similar problems with obsolete major interfaces and limited link speeds and processing capabilities. A new common card has been developed to enable the upgrade of the read-out chain towards higher link rates while providing backward compatibility with the current architecture. First prototypes could be tested successfully and raised interest from other collaborations.

  15. Fully digital readout of segmented solid state detectors

    NASA Astrophysics Data System (ADS)

    Blumenhagen, K. H.; Badura, E.; Bräuning, H.; Hoffmann, J.; Koch, K.; Kurz, N.; Märtin, R.; Minami, S.; Ott, W.; Spillmann, U.; Stöhlker, Th; Weber, G.; Weber, M.

    2013-09-01

    In this work, the digital readout of semiconductor detectors in combination with digital filters was investigated. Both non-segmented high-purity germanium and segmented planar lithium-drifted silicon detectors were used. In each case, photons from a stationary americium (241Am) gamma source were detected. The resulting preamplifier output pulses were digitized at a fixed sampling frequency and stored entirely. Digital filters were applied to the stored waveforms to extract time and energy information. The performance of different digital filters was compared. The optimum energy resolution obtained was comparable with the value resulting from an analogue readout system based on standard nuclear instrumentation module and versatile module Europe bus electronics.

  16. Vertically integrated pixel readout chip for high energy physics

    SciTech Connect

    Deptuch, Grzegorz; Demarteau, Marcel; Hoff, James; Khalid, Farah; Lipton, Ronald; Shenai, Alpana; Trimpl, Marcel; Yarema, Raymond; Zimmerman, Tom; /Fermilab

    2011-01-01

    We report on the development of the vertex detector pixel readout chips based on multi-tier vertically integrated electronics for the International Linear Collider. Some testing results of the VIP2a prototype are presented. The chip is the second iteration of the silicon implementation of the prototype, data-pushed concept of the readout developed at Fermilab. The device was fabricated in the 3D MIT-LL 0.15 {micro}m fully depleted SOI process. The prototype is a three-tier design, featuring 30 x 30 {micro}m{sup 2} pixels, laid out in an array of 48 x 48 pixels.

  17. Probing the Speed Limits of Transmon Dispersive Readout

    NASA Astrophysics Data System (ADS)

    Walter, Theo; Kurpiers, Philipp; Mondal, Mintu; Pechal, Marek; Wallraff, Andreas

    In circuit QED, faster and more accurate measurement of a qubit's state is necessary to achieve better feedback control, to accomplish more complex quantum algorithms and simulations, and to cross the threshold for fault tolerant quantum computing. In this talk, we discuss our experimental progress to minimize the time needed to readout the state of a dispersively coupled transmon qubit with high fidelity. We outline a signal-to-noise ratio model, illuminate the constraints and find optimal parameters for maximizing measurement speed, while maintaining high readout fidelity. Utilizing a Purcell Filter increases the generality of our results as it becomes possible to reach these speeds with a broader set of system parameters.

  18. A fast readout and processing electronics for photon counting intensified charge-coupled device

    NASA Astrophysics Data System (ADS)

    Bergamini, P.; Bonelli, G.; Tanzi, E. G.; Uslenghi, M.; Poletto, L.; Tondello, G.

    2000-04-01

    The design features and the performances of a prototype photon counting imaging detector, being developed for the international ultraviolet (UV) space mission Spectrum UV, are presented. The photon counter is an intensified charge coupled device (ICCD) in which photon events, generating an electron cascade through a high gain microchannel plate (MCP) stack, are transduced, via a phosphor screen and a fiber optics reducer, into a 3×3 pixel2, quasi-Gaussian charge distributions on a 15×15 μm2,512×512 pixel2 format CCD matrix. The CCD is read out in the frame-transfer mode at a pixel rate of 19.75 MHz, and its output data flow is acquired serially as to generate a 3×3 pixel2 event sash that sweeps dynamically the CCD matrix at the 50.6 ns rate of the readout clock. Each and every event sash is searched for the presence of events whose charge content lie within proper limits and satisfy a given set of morphological rules, i.e., a single peak charge profile. The centroid coordinates of identified events are determined with subpixel accuracy (up to a 210 bin/pixel) and subsequently stored as photon list coordinate pairs. The data acquisition and processing system is based on field programmable gate array technology and is capable of satisfying the requirements of real-time operation. The modular construction of the data acquisition and processing electronics provides a great deal of flexibility for supporting advancements in CCD readout techniques (multiple output and higher clocking speed) and of MCPs (larger formats, smaller pore, and higher dynamic range). The results of the performance verification of the data acquisition and processing system integrated with a laboratory ICCD prototype are presented and discussed.

  19. Metal Ion-dependent Heavy Chain Transfer Activity of TSG-6 Mediates Assembly of the Cumulus-Oocyte Matrix*

    PubMed Central

    Briggs, David C.; Birchenough, Holly L.; Ali, Tariq; Rugg, Marilyn S.; Waltho, Jon P.; Ievoli, Elena; Jowitt, Thomas A.; Enghild, Jan J.; Richter, Ralf P.; Salustri, Antonietta; Milner, Caroline M.; Day, Anthony J.

    2015-01-01

    The matrix polysaccharide hyaluronan (HA) has a critical role in the expansion of the cumulus cell-oocyte complex (COC), a process that is necessary for ovulation and fertilization in most mammals. Hyaluronan is organized into a cross-linked network by the cooperative action of three proteins, inter-α-inhibitor (IαI), pentraxin-3, and TNF-stimulated gene-6 (TSG-6), driving the expansion of the COC and providing the cumulus matrix with its required viscoelastic properties. Although it is known that matrix stabilization involves the TSG-6-mediated transfer of IαI heavy chains (HCs) onto hyaluronan (to form covalent HC·HA complexes that are cross-linked by pentraxin-3) and that this occurs via the formation of covalent HC·TSG-6 intermediates, the underlying molecular mechanisms are not well understood. Here, we have determined the tertiary structure of the CUB module from human TSG-6, identifying a calcium ion-binding site and chelating glutamic acid residue that mediate the formation of HC·TSG-6. This occurs via an initial metal ion-dependent, non-covalent, interaction between TSG-6 and HCs that also requires the presence of an HC-associated magnesium ion. In addition, we have found that the well characterized hyaluronan-binding site in the TSG-6 Link module is not used for recognition during transfer of HCs onto HA. Analysis of TSG-6 mutants (with impaired transferase and/or hyaluronan-binding functions) revealed that although the TSG-6-mediated formation of HC·HA complexes is essential for the expansion of mouse COCs in vitro, the hyaluronan-binding function of TSG-6 does not play a major role in the stabilization of the murine cumulus matrix. PMID:26468290

  20. Metal Ion-dependent Heavy Chain Transfer Activity of TSG-6 Mediates Assembly of the Cumulus-Oocyte Matrix.

    PubMed

    Briggs, David C; Birchenough, Holly L; Ali, Tariq; Rugg, Marilyn S; Waltho, Jon P; Ievoli, Elena; Jowitt, Thomas A; Enghild, Jan J; Richter, Ralf P; Salustri, Antonietta; Milner, Caroline M; Day, Anthony J

    2015-11-27

    The matrix polysaccharide hyaluronan (HA) has a critical role in the expansion of the cumulus cell-oocyte complex (COC), a process that is necessary for ovulation and fertilization in most mammals. Hyaluronan is organized into a cross-linked network by the cooperative action of three proteins, inter-α-inhibitor (IαI), pentraxin-3, and TNF-stimulated gene-6 (TSG-6), driving the expansion of the COC and providing the cumulus matrix with its required viscoelastic properties. Although it is known that matrix stabilization involves the TSG-6-mediated transfer of IαI heavy chains (HCs) onto hyaluronan (to form covalent HC·HA complexes that are cross-linked by pentraxin-3) and that this occurs via the formation of covalent HC·TSG-6 intermediates, the underlying molecular mechanisms are not well understood. Here, we have determined the tertiary structure of the CUB module from human TSG-6, identifying a calcium ion-binding site and chelating glutamic acid residue that mediate the formation of HC·TSG-6. This occurs via an initial metal ion-dependent, non-covalent, interaction between TSG-6 and HCs that also requires the presence of an HC-associated magnesium ion. In addition, we have found that the well characterized hyaluronan-binding site in the TSG-6 Link module is not used for recognition during transfer of HCs onto HA. Analysis of TSG-6 mutants (with impaired transferase and/or hyaluronan-binding functions) revealed that although the TSG-6-mediated formation of HC·HA complexes is essential for the expansion of mouse COCs in vitro, the hyaluronan-binding function of TSG-6 does not play a major role in the stabilization of the murine cumulus matrix.

  1. Matrine inhibits IL-1β-induced expression of matrix metalloproteinases by suppressing the activation of MAPK and NF-κB in human chondrocytes in vitro.

    PubMed

    Lu, Shijin; Xiao, Xungang; Cheng, Minghua

    2015-01-01

    Interleukin (IL)-1β plays an important role in promoting osteoarthritis (OA) lesions by inducing chondrocytes to secrete matrix metalloproteinases (MMPs), which degrade the extracellular matrix and facilitate chondrocyte apoptosis. Matrine was shown to exert anti-inflammatory effects. However, the role of matrine in OA is still unclear. Therefore, in this study, we investigated the effects of matrine on the expression of MMPs in IL-1β-treated human chondrocytes and the underlying mechanism. The cell viability of chondrocytes was detected by MTT assay. The cell apoptosis of chondrocytes was measured by flow cytometric analysis. The protein production of MMPs was determined by ELISA. The protein expression of phosphorylation of mitogen-activated protein kinases (MAPKs) and the inhibitor of kappaB alpha (IκBα) was determined by Western blot. Matrine significantly inhibited the IL-1β-induced apoptosis in chondrocytes. It also significantly inhibited the IL-1β-induced release of MMP-3 and MMP-13, and increased the production of TIMP-1. Furthermore, matrine inhibits the phosphorylation of p-38, extracellular regulated kinase (ERK), c-Jun-N-terminal kinase (JNK) and IκBα degradation induced by IL-1β in chondrocytes. Taken together, our results show that matrine inhibits IL-1β-induced expression of matrix metalloproteinases by suppressing the activation of MAPK and NF-κB in human chondrocytes in vitro. Therefore,-matrine may be beneficial in the treatment of OA.

  2. Activity concentration measurements of 137Cs, 90Sr and 40K in a wild food matrix reference material (Wild Berries) CCRI(II)-S8

    NASA Astrophysics Data System (ADS)

    Wätjen, U.; Altzitzogloa, T.; Ceccatelli, A.; Dikmen, H.; Ferreux, L.; Frechou, C.; García, L.; Gündogdu, G.; Kis-Benedek, G.; La Rosa, J.; Luca, A.; Moreno, Y.; Oropesa, P.; Pierre, S.; Schmiedel, M.; Spasova, Y.; Szücs, L.; Vasile, M.; Wershofen, H.; Yücel, Ü.

    2014-01-01

    In 2009, the CCRI approved a supplementary comparison to be organized by the IRMM as pilot laboratory for the activity concentrations of 137Cs, 90Sr and 40K in a matrix material of dried bilberries. The organization of this comparison and the material and measurement methods used are described. The supplementary comparison reference values (SCRV) for each of the three radionuclides are given together with the degrees of equivalence of each participating laboratory with the SCRV for the specific radionuclide. The results of this supplementary comparison allow the participating NMIs/designated institutes to declare calibration and measurement capabilities (CMCs) for the given radionuclides in a similar type of food matrix, an important aspect given the relatively few supplementary comparisons for activity in matrix materials organized so far. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  3. Non-invasive dual fluorescence in vivo imaging for detection of macrophage infiltration and matrix metalloproteinase (MMP) activity in inflammatory arthritic joints

    PubMed Central

    Cho, Hongsik; Bhatti, Fazal-Ur-Rehman; Yoon, Tae Won; Hasty, Karen A.; Stuart, John M.; Yi, Ae-Kyung

    2016-01-01

    Detection and intervention at an early stage is a critical factor to impede arthritis progress. Here we present a non-invasive method to detect inflammatory changes in joints of arthritic mice. Inflammation was monitored by dual fluorescence optical imaging for near-infrared fluorescent (750F) matrix-metalloproteinase activatable agent and allophycocyanin-conjugated anti-mouse CD11b. Increased intensity of allophycocyanin (indication of macrophage accumulation) and 750F (indication of matrix-metalloproteinase activity) showed a biological relationship with the arthritis severity score and the histopathology score of arthritic joints. Our results demonstrate that this method can be used to detect early stages of arthritis with minimum intervention in small animal models. PMID:27231625

  4. Inhibitory Effects of Isorhamnetin on the Invasion of Human Breast Carcinoma Cells by Downregulating the Expression and Activity of Matrix Metalloproteinase-2/9.

    PubMed

    Li, Chenglin; Yang, Dan; Zhao, Yuanwei; Qiu, Yu; Cao, Xin; Yu, Yanyan; Guo, Hao; Gu, Xiaoke; Yin, Xiaoxing

    2015-01-01

    Matrix metalloproteinases (MMPs) play an active role in facilitating the invasion of cancer cells with excessive extracellular matrix (ECM) degradation. In the present study, we investigated the antiinvasive effects of isorhamnetin, a naturally occurring flavonoid, on MDA-MB-231 human breast carcinoma cells. The results indicated that isorhamnetin significantly inhibited the adhesion, migration, and invasion of the cells in vitro. Moreover, isorhamnetin suppressed the activity and expression of MMP-2 and MMP-9, which were determined by gelatin zymography, real-time PCR, and Western blot analysis, respectively. Besides, isorhamnetin had little effect on the secretion of urokinase plasminogen activator. Further elucidation of the mechanism revealed that isorhamnetin exerted an inhibitory effect on the phosphorylation of p38 and STAT3, although it had no effect on ERK1/2 and JNK. Taken together, these data demonstrated that isorhamnetin could significantly inhibit the invasion of MDA-MB-231 cells by downregulating the expression and activity of MMP-2 and MMP-9, which was potentially associated with the suppression of p38 MAPK and STAT3. Therefore, the findings provide new evidence for the anti-cancer activity of isorhamnetin. PMID:26359917

  5. Adaptive Readout Technique For A Sixteen Channel Peak Sensing ADC In the FERA Format

    SciTech Connect

    Yaver, H.; Maier, M.R.; Lindstrom, D.; Ludewigt, B.A.

    1998-11-01

    An adaptive, variable block-size readout technique for use with multiple, sixteen-channel CAMAC ADCs with a FERA-bus readout has been developed and designed. It can be used to read data from experiments with or without coincidence, i.e. singles, without having to change the readout protocol. Details of the implementation are discussed and initial results are presented. Further applications of the adaptive readout are also discussed.

  6. Compact, Low-power and Precision Timing Photodetector Readout

    SciTech Connect

    Varner, Gary S.; Ruckman, Larry L.; Schwiening, Jochen; Vavra, Jaroslav; /SLAC

    2011-06-14

    Photodetector readout for next generation high event rate particle identification and single-photon detection requires a digitizer capable of integrated recording of dense arrays of sensor elements with high analog bandwidth (precision timing) and large record depth, in a cost-effective, compact and low-power way. Simply stated, one cannot do better than having a high-fidelity 'oscilloscope on a chip' for every sensor channel. A firs version of the Buffered Large Analog Bandwidth (BLAB1) ASIC has been designed based upon the lessons learned from the development of the Large Analog Bandwidth Recorder and Digitizer with Ordered Readout (LABRADOR) ASIC. While this LABRADOR ASIC has been very successful and forms the readout basis of a generation of new, large-scale radio neutrino detectors, its limited sampling depth is a major drawback. To address this shortcoming, a prototype intended for photodetector readout has been designed and fabricated with 64k deep sampling at multi-GSa/s operation. An evaluation system has been constructed for instrumentation of Time-Of-Propagation (TOP) and focusing DIRC prototypes and test results will be reported.

  7. Optimized readout system for cooled optically stimulated luminescence

    NASA Astrophysics Data System (ADS)

    Miller, S. D.; Eschbach, P. A.

    1990-09-01

    Cooled Optically Stimulated Luminescence (COSL) in CaF2:Mn is an ionizing radiation dosimetry method recently developed at the Pacific Northwest Laboratory (PNL). In this method CaF2:Mn crystals irradiated by gamma radiation at room temperature are cooled to liquid nitrogen temperature (77 K), stimulated by ultraviolet laser light at 326 nm, and allowed to warm to room temperature. Light emission proportional to the gamma exposure occurs as the TLD warms from liquid nitrogen temperature to room temperature. The new method is an example of a highly sensitive phototransfer technique which could form the basis for future radiation dosimetry applications. Measurements to date have shown high potential for measuring gamma exposures in the range of 10 microR. The high sensitivity of the COSL technique is due in part to the larger quantum efficiency of radiative recombination at low temperatures and to the complete absence of the incandescent background associated with conventional thermoluminescent readout methods. Along with the potential for a system which is more sensitive than thermoluminescent readers, multiple COSL readouts can be performed with minimal reduction in the COSL intensity. The multiple readout capability can serve as a possible permanent dosimetry record, thus allowing the reanalysis of a questionable reading. In an attempt to optimize the sensitivity of the COSL method, a new readout system is being developed.

  8. A generic readout environment for prototype pixel detectors

    NASA Astrophysics Data System (ADS)

    Turqueti, Marcos; Rivera, Ryan; Prosser, Alan; Kwan, Simon

    2010-11-01

    Pixel detectors for experimental particle physics research have been implemented with a variety of readout formats and potentially generate massive amounts of data. Examples include the PSI46 device for the Compact Muon Solenoid (CMS) experiment which implements an analog readout, the Fermilab FPIX2.1 device with a digital readout, and the Fermilab Vertically Integrated Pixel device. The Electronic Systems Engineering Department of the Computing Division at the Fermi National Accelerator Laboratory has developed a data acquisition system flexible and powerful enough to meet the various needs of these devices to support laboratory test bench as well as test beam applications. The system is called CAPTAN (Compact And Programmable daTa Acquisition Node) and is characterized by its flexibility, versatility and scalability by virtue of several key architectural features. These include a vertical bus that permits the user to stack multiple boards, a gigabit Ethernet link that permits high speed communications to the system and a core group of boards that provide specific processing and readout capabilities for the system. System software based on distributed computing techniques supports an expandable network of CAPTANs. In this paper, we describe the system architecture and give an overview of its capabilities.

  9. MTR CONTROL ROOM WITH CONTROL CONSOLE AND STATUS READOUTS ALONG ...

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

    MTR CONTROL ROOM WITH CONTROL CONSOLE AND STATUS READOUTS ALONG WALL. WORKERS MAKE ELECTRICAL AND OTHER CONNECTIONS. INL NEGATIVE NO. 4289. Unknown Photographer, 2/26/1952 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  10. Spatial distribution read-out system for thermoluminescence sheets

    NASA Technical Reports Server (NTRS)

    Yamamoto, I.; Tomiyama, T.; Imaeda, K.; Ninagawa, K.; Wada, T.; Yamashita, Y.; Misaki, A.

    1985-01-01

    A spatial distribution read-out system of thermoluminescence (TL) sheets is developed. This system consists of high gain image intensifier, a CCD-TV camera, a video image processor and a host computer. This system has been applied to artificial TL sheets (BaSO4:Eu doped) for detecting high energy electromagnetic shower and heavy nuclei tracks.

  11. Optical Readout of Micro-Accelerometer Code Features

    SciTech Connect

    Dickey, Fred M.; Holswade, Scott C.; Polosky, Marc A.; Shagam, Richard N.; Sullivan, Charles T.

    1999-07-08

    Micromachine accelerometers offer a way to enable critical functions only when a system encounters a particular acceleration environment. This paper describes the optical readout of a surface micromachine accelerometer containing a unique 24-bit code. The readout uses waveguide-based optics, which are implemented as a photonic integrated circuit (PIC). The PIC is flip-chip bonded over the micromachine, for a compact package. The shuttle moves 500 {micro}m during readout, and each code element is 17 {micro}m wide. The particular readout scheme makes use of backscattered radiation from etched features in the accelerometer shuttle. The features are etched to create corner reflectors that return radiation back toward the source for a one bit. For a zero bit, the shuttle is not etched, and the radiation scatters forward, away from the detector. This arrangement provides a large signal difference between a one and zero signal, since the zero signal returns virtually no signal to the detector. It is thus superior to schemes that interrogate the code vertically, which have a limited contrast between a one and a zero. Experimental results are presented for mock shuttle features etched into a silicon substrate. To simulate the shuttle moving under a fixed PIC, a commercially available waveguide source was scanned over the mock code.

  12. Sources of noise in magneto-optical readout

    NASA Technical Reports Server (NTRS)

    Mansuripur, M.

    1991-01-01

    The various sources of noise which are often encountered in magneto-optical readout systems are analyzed. Although the focus is on magneto-optics, most sources of noise are common among the various optical recording systems and one can easily adapt the results to other media and systems. A description of the magneto-optical readout system under consideration is given, and the standard methods and the relevant terminology of signal and noise measurement are described. The characteristics of thermal noise, which originates in the electronic circuitry of the readout system, are described. The most fundamental of all sources of noise, the shot noise, is considered, and a detailed account of its statistical properties is given. Shot noise, which is due to random fluctuations in photon arrival times, is an ever-present noise in optical detection. Since the performance of magneto-optical recording devices in use today is approaching the limit imposed by the shot noise, it is important that the reader have a good grasp of this particular source of noise. A model for the laser noise is described, and measurement results which yield numerical values for the strength of the laser power fluctuations are presented. Spatial variations of the disk reflectivity and random depolarization phenomena also contribute to the overall level of noise in readout; these and related issues are treated. Numerical simulation results describing some of the more frequently encountered sources of noise which accompany the recorded waveform itself, namely, jitter noise and signal-amplitude fluctuation noise are presented.

  13. Triple-stack multigap resistive plate chamber with strip readout

    NASA Astrophysics Data System (ADS)

    Babkin, V.; Basilev, S.; Buryakov, M.; Golovatyuk, V.; Lobastov, S.; Petrov, V.; Rumyantsev, M.; Schipunov, A.; Shutov, A.; Slepnev, I.; Slepnev, V.

    2016-07-01

    A triple-stack MRPC for the TOF system of the BM@N and the MPD experiments at the future collider NICA was tested. We use three stacks of glass to have symmetrical construction which allows to decrease dispersion and reflections of the signal from the readout strip.

  14. 46 CFR 154.1375 - Readout for temperature measuring device: Marking.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Readout for temperature measuring device: Marking. 154..., Construction and Equipment Instrumentation § 154.1375 Readout for temperature measuring device: Marking. Each readout under § 154.1340 for a device that measures temperature in a cargo tank must be marked with...

  15. 46 CFR 154.1375 - Readout for temperature measuring device: Marking.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Readout for temperature measuring device: Marking. 154..., Construction and Equipment Instrumentation § 154.1375 Readout for temperature measuring device: Marking. Each readout under § 154.1340 for a device that measures temperature in a cargo tank must be marked with...

  16. 46 CFR 154.1375 - Readout for temperature measuring device: Marking.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Readout for temperature measuring device: Marking. 154..., Construction and Equipment Instrumentation § 154.1375 Readout for temperature measuring device: Marking. Each readout under § 154.1340 for a device that measures temperature in a cargo tank must be marked with...

  17. 46 CFR 154.1375 - Readout for temperature measuring device: Marking.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Readout for temperature measuring device: Marking. 154..., Construction and Equipment Instrumentation § 154.1375 Readout for temperature measuring device: Marking. Each readout under § 154.1340 for a device that measures temperature in a cargo tank must be marked with...

  18. 46 CFR 154.1375 - Readout for temperature measuring device: Marking.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Readout for temperature measuring device: Marking. 154..., Construction and Equipment Instrumentation § 154.1375 Readout for temperature measuring device: Marking. Each readout under § 154.1340 for a device that measures temperature in a cargo tank must be marked with...

  19. Anti-tumor effects of Rubratoxin B on cell toxicity, inhibition of cell proliferation, cytotoxic activity and matrix metalloproteinase-2,9.

    PubMed

    Wang, Tao; Zhang, Yi; Wang, Yi; Pei, Yue-hu

    2007-06-01

    Terrestrial fungi are a prolific source of metabolites with significant biological activities. Many important anticancer, antifungal and antibacterial chemotherapeutics are either microbial metabolites or semisynthetic derivatives. Investigating the metabolites of fungi may increase the chance of finding novel compounds. A bioassay-guided fractionation of soil fungus Penicillium purpurogenum fermentation, yielded the metabolite Rubratoxin B using morphological deformation of Pyricularia oryzae mycelia. Analysis by flow cytometry showed that Rubratoxin B inhibited the cell cycle progression of tsFT210 cells in the G2/M phase at the concentration of 24 microM. Cytotoxic activity analysis showed that Rubratoxin B has a cytotoxic activity and IC50 was 67.3 +/- 1.4 microM on human fibrosarcoma cell (HT1080), and Rubratoxin B exhibited inhibitory activities against matrix metalloproteinase (MMP)-2 and 9 on HT 1080 cells with an inhibitory rate of 61.5% and 74.7% at 30 microM, respectively. PMID:17306501

  20. Digital readouts for large microwave low-temperature detector arrays

    NASA Astrophysics Data System (ADS)

    Mazin, Benjamin A.; Day, Peter K.; Irwin, Kent D.; Reintsema, Carl D.; Zmuidzinas, Jonas

    2006-04-01

    Over the last several years many different types of low-temperature detectors (LTDs) have been developed that use a microwave resonant circuit as part of their readout. These devices include microwave kinetic inductance detectors (MKID), microwave SQUID readouts for transition edge sensors (TES), and NIS bolometers. Current readout techniques for these devices use analog frequency synthesizers and IQ mixers. While these components are available as microwave integrated circuits, one set is required for each resonator. We are exploring a new readout technique for this class of detectors based on a commercial-off-the-shelf technology called software defined radio (SDR). In this method a fast digital to analog (D/A) converter creates as many tones as desired in the available bandwidth. Our prototype system employs a 100 MS/s 16-bit D/A to generate an arbitrary number of tones in 50 MHz of bandwidth. This signal is then mixed up to the desired detector resonant frequency (˜10 GHz), sent through the detector, then mixed back down to baseband. The baseband signal is then digitized with a series of fast analog to digital converters (80 MS/s, 14-bit). Next, a numerical mixer in a dedicated integrated circuit or FPGA mixes the resonant frequency of a specified detector to 0 Hz, and sends the complex detector output over a computer bus for processing and storage. In this paper we will report on our results in using a prototype system to readout a MKID array, including system noise performance, X-ray pulse response, and cross-talk measurements. We will also discuss how this technique can be scaled to read out many thousands of detectors.

  1. On readout of vibrational qubits using quantum beats

    SciTech Connect

    Shyshlov, Dmytro; Babikov, Dmitri; Berrios, Eduardo; Gruebele, Martin

    2014-12-14

    Readout of the final states of qubits is a crucial step towards implementing quantum computation in experiment. Although not scalable to large numbers of qubits per molecule, computational studies show that molecular vibrations could provide a significant (factor 2–5 in the literature) increase in the number of qubits compared to two-level systems. In this theoretical work, we explore the process of readout from vibrational qubits in thiophosgene molecule, SCCl{sub 2}, using quantum beat oscillations. The quantum beats are measured by first exciting the superposition of the qubit-encoding vibrational states to the electronically excited readout state with variable time-delay pulses. The resulting oscillation of population of the readout state is then detected as a function of time delay. In principle, fitting the quantum beat signal by an analytical expression should allow extracting the values of probability amplitudes and the relative phases of the vibrational qubit states. However, we found that if this procedure is implemented using the standard analytic expression for quantum beats, a non-negligible phase error is obtained. We discuss the origin and properties of this phase error, and propose a new analytical expression to correct the phase error. The corrected expression fits the quantum beat signal very accurately, which may permit reading out the final state of vibrational qubits in experiments by combining the analytic fitting expression with numerical modelling of the readout process. The new expression is also useful as a simple model for fitting any quantum beat experiments where more accurate phase information is desired.

  2. Optimal CCD readout by digital correlated double sampling

    NASA Astrophysics Data System (ADS)

    Alessandri, C.; Abusleme, A.; Guzman, D.; Passalacqua, I.; Alvarez-Fontecilla, E.; Guarini, M.

    2016-01-01

    Digital correlated double sampling (DCDS), a readout technique for charge-coupled devices (CCD), is gaining popularity in astronomical applications. By using an oversampling ADC and a digital filter, a DCDS system can achieve a better performance than traditional analogue readout techniques at the expense of a more complex system analysis. Several attempts to analyse and optimize a DCDS system have been reported, but most of the work presented in the literature has been experimental. Some approximate analytical tools have been presented for independent parameters of the system, but the overall performance and trade-offs have not been yet modelled. Furthermore, there is disagreement among experimental results that cannot be explained by the analytical tools available. In this work, a theoretical analysis of a generic DCDS readout system is presented, including key aspects such as the signal conditioning stage, the ADC resolution, the sampling frequency and the digital filter implementation. By using a time-domain noise model, the effect of the digital filter is properly modelled as a discrete-time process, thus avoiding the imprecision of continuous-time approximations that have been used so far. As a result, an accurate, closed-form expression for the signal-to-noise ratio at the output of the readout system is reached. This expression can be easily optimized in order to meet a set of specifications for a given CCD, thus providing a systematic design methodology for an optimal readout system. Simulated results are presented to validate the theory, obtained with both time- and frequency-domain noise generation models for completeness.

  3. A close relationship between type 1 diabetes and vitamin A-deficiency and matrix metalloproteinase and hyaluronidase activities in skin tissues.

    PubMed

    Takahashi, Noriko; Takasu, Shingo

    2011-11-01

    Numerous wrinkles are observed in the skin of streptozotocin (STZ)-induced type 1 diabetic rats, which are similar to those seen in vitamin A-deficient (VAD) rats. Retinoic acid (RA), the active form of vitamin A, promotes the production of collagen in dermis and induces cell growth and inhibition of epidermal differentiation in skin tissues. Normal skin function is maintained by the extracellular matrix (ECM)-degrading enzymes, matrix metalloproteinase (MMP) and hyaluronidase (HAase). This study is the first comparison of MMP and HAase activities in skin tissues of type 1 diabetic, VAD and RA-treated animal models. In skin tissues of type 1 diabetic and VAD rats or VAD mice, both MMP-2 and HAase activities increased as compared with controls. In contrast, MMP and HAase activities were reduced in the skin tissues of RA-treated mice. Blood retinol levels in type 1 diabetic rats were lower than controls. These results indicate a close relationship between type 1 diabetes and vitamin A-deficiency on MMP and HAase in skin tissues, suggesting that type 1 diabetic rats could be vitamin A-deficient. Vitamin A-derived RA might be a significant regulator of ECM-degrading enzyme expression and diabetic symptoms.

  4. [Autoradiographic investigations on postnatal proliferative activity of the telencephalic and diencephalic matrix-zones in the axolotl (Ambystoma mexicanum), with special references to the olfactory organ (author's transl)].

    PubMed

    Richter, W; Kranz, D

    1981-01-01

    The localization and proliferative activity of the matrix-zones has been investigated in the telencephalon and in the diencephalon of 21 axolotls (Ambystoma mexicanum) by means of autoradiographs, after injection of tritiated thymidine at different stages of the postnatal life. There are no previous detailed autoradiographical reports on postnatal brain development in the axolotl. Matrix-zones (i.e. ventricular and subventricular zone) exist in the dorsal part and in the ventral part of the telencephalon, we have found these also in the diencephalon in the wall of the preoptic recessus and ventrally of the habenula. The quantitative part of this study indicates high values of the labeling-index in the early postnatal stages. Then, the labeling-index decreases, but also in 3 years old specimens labeled cells were observed in the matrix-zones of the telencephalon; therefore a few of proliferative capacity remains in the central nervous system of adult axolotls. Labeled cells were also found in the olfactory organ of early postnatal and adult axolotls; these are neuroblasts which have relevance for the regeneration of the forebrain.

  5. The influence of resveratrol on the synovial expression of matrix metalloproteinases and receptor activator of NF-kappaB ligand in rheumatoid arthritis fibroblast-like synoviocytes.

    PubMed

    Glehr, Mathias; Breisach, Margherita; Walzer, Sonja; Lohberger, Birgit; Fürst, Florentine; Friesenbichler, Joerg; Rinner, Beate; Avian, Alexander; Windhager, Reinhard; Leithner, Andreas

    2013-01-01

    Medication of rheumatoid arthritis (RA) remains challenging and often controversial concerning side effects or long-term complications. We investigated the effect of resveratrol, a phytoalexin discussed for its chondro-protective and anti-inflammatory qualities, on the synovial expression of matrix-degrading enzymes like matrix metalloproteinases (MMPs) and bone-remodelling proteins in RA fibroblast-like synoviocytes (FLS). Interleukin-1beta-stimulated RA-FLS were treated with 100 microM resveratrol for 24 h. To evaluate the effect of resveratrol on the amount of bound/combined MMPs, a Luminex xMAP multiplexing technology was used. The alteration in expression of receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegrin (OPG) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Resveratrol reduced the expression of MMP-1 (p = 0.022), MMP-3 (p = 0.021), and MMP-9 (p = 0.047). qRT-PCR showed a significant reduction in the relative abundance of the transcripts of OPG (p = 0.012) and RANKL (p = 0.018). Our in vitro findings indicate that resveratrol could be a new target for further pharmacological studies in the field of RA. In the future it could play a role as a possible substitute or supplement to currently used drugs against RA to prevent cartilage matrix degradation and pathological bone resorption due to inhibition of MMPs and RANKL.

  6. Methane activation by laser-ablated Th atoms: matrix infrared spectra and theoretical investigations of CH₃-Th-H and CH₂═ThH₂.

    PubMed

    Cho, Han-Gook; Andrews, Lester

    2015-03-19

    Methane activation by laser-ablated Th atoms on the triplet potential energy surface produces the methylthorium hydride, CH3-Th-H, that converts smoothly by α-H transfer to CH2-ThH2, which relaxes in the matrix to the more stable singlet methylidene, CH2═ThH2. This first actinide methylidene was characterized from argon matrix infrared spectra and B3LYP calculations in our laboratory. We now report neon matrix investigations, which include the methylthorium hydride and the Th-D stretching modes of CD2═ThD2 that are blue-shifted in neon from under the intense CD4 precursor absorption, and reactions with CH2D2 that give rise to the CHD═ThHD modifications and their α-H and α-D transfer counterparts CD2═ThH2 and CH2═ThD2. New intrinsic reaction coordinate calculations show that this reaction proceeds smoothly on the triplet potential energy surface. PMID:25054638

  7. Matrix isolation investigation of the photochemical reaction of activator-substituted benzenes with CrCl 2O 2

    NASA Astrophysics Data System (ADS)

    Hoops, Michael D.; Ault, Bruce S.

    2008-10-01

    The matrix isolation technique, combined with infrared spectroscopy and theoretical calculations, has been used to characterize the products of the photochemical reactions of aniline, anisole, and N, N-dimethylaniline with CrCl 2O 2. While initial twin jet deposition of the reagents did not lead to product formation, new bands were noted following irradiation with light of λ > 300 nm. In the reactions of CrCl 2O 2 and aniline, irradiation led to HCl formation, very likely accompanied by CrClO 2(H)NC 6H 5 formation, and a mixture of isomers of CrCl 2O-aminocyclohexa-2,4-dienone via oxygen atom transfer. CrCl 2O 2 and aniline were also codeposited as cryogenic thin films, producing new bands. Irradiation of these films led to further growth of these bands. The same products were identified in the thin film studies as were observed in the argon matrix experiments. The irradiation of the matrices containing CrCl 2O 2 and anisole and N, N-dimethylaniline were shown to lead to oxygen atom transfer, forming complexes between the corresponding cyclic ketone derivatives and CrCl 2O. The identification of the complexes were supported by density functional calculations at the B3LYP/6-311G++(d,2p) level and isotopic labeling (in the case of aniline).

  8. Application of matrix calculation 1: Design and adjustment of a tandem mass spectrometer for Collision-Activated Dissociation (CAD)

    NASA Astrophysics Data System (ADS)

    1982-02-01

    A matrix representation of the ion optics of the analyzing stage has been used in a computer model of a tandem mass spectrometer with simultaneous detection for CAD. The matrix algorithm of this model is discussed here as an elegant way of describing the ion optics in a first-order approximation. The accuracy of the calculations is illustrated by comparing calculated and measured adjustments of the instrument under normal experiment conditions. The ion-optical possibilities with respect to transmission, mass resolution influence of several ion optical parameters on the shape and position of the mass focal plane is discussed. The experimental values of mass range, mass resolution and ion transmission agree very well with the calculations. Moreover, the computer model appears to be a useful tool for giving clear insight into the operation of the rather complex ion optics of the instrument. The calculations have been further developed towards higher accuracy, making possible automatic focusing of the mass focal plane onto the detector.

  9. Modeling the Effect of Active Fiber Cooling on the Microstructure of Fiber-Reinforced Metal Matrix Composites

    NASA Astrophysics Data System (ADS)

    Nguyen, Nguyen Q.; Peterson, Sean D.; Gupta, Nikhil; Rohatgi, Pradeep K.

    2009-08-01

    A modified pressure infiltration process was recently developed to synthesize carbon-fiber-reinforced aluminum matrix composites. In the modified process, the ends of carbon fibers are extended out of the crucible to induce selective cooling. The process is found to be effective in improving the quality of composites. The present work is focused on determining the effect of the induced conductive heat transfer on the composite system through numerical methods. Due to the axisymmetry of the system, a two-dimensional (2-D) model is studied that can be expanded into three dimensions. The variables in this transient analysis include the fiber radius, fiber length, and melt superheat temperature. The results show that the composite system can be tailored to have a temperature on the fiber surface that is lower than the melt, to promote nucleation on the fiber surface. It is also observed that there is a point of inflection in the temperature profile along the particle/melt interface at which there is no temperature gradient in the radial direction. The information about the inflection point can be used to control the diffusion of solute atoms in the system. The result can be used in determining the optimum fiber volume fraction in metal matrix composite (MMC) materials to obtain the desired microstructure.

  10. Thermal activated energy transfer between luminescent states of Mn2+-doped ZnTe nanoparticles embedded in a glass matrix.

    PubMed

    Dantas, Noelio O; Silva, Alessandra S; Freitas Neto, Ernesto S; Lourenço, Sidney A

    2012-03-14

    Zn(1-x)Mn(x)Te nanocrystals (NCs), at various concentrations x, were successfully grown in a host glass matrix by the fusion method after appropriate annealing. Growth of these NCs was evidenced by optical absorption (OA), X-Ray Diffraction (XRD), magnetic force microscopy (MFM) and photoluminescence (PL) measurements. From the room temperature OA spectra, it was possible to observe the formation of two well defined, different sized groups of NCs, one attributed to quantum dots (QDs) and the other to bulk-like nanocrystals (NCs). XRD results have confirmed that the cubic zincblend structure of nanoparticles is not altered by the substitutional incorporation of Mn(2+) ions into the ZnTe NCs. MFM images supported the OA spectra results and thus provided additional confirmation of the formation of Zn(1-x)Mn(x)Te magnetic nanoparticles in the host glass matrix. The two groups of NCs were also observed in the PL spectra as well as deep defects attributed to the presence of oxygen centers in the electronic structure of the Zn(1-x)Mn(x)Te NCs. Strong agreement between the fitting model, based on rate equation, and experimental PL intensity data at different temperatures demonstrates that this model adequately describes the energy transfer processes between the NCs and the defects of the Zn(1-x)Mn(x)Te system at different temperatures.

  11. High glucose enhances microRNA-26a to activate mTORC1 for mesangial cell hypertrophy and matrix protein expression

    PubMed Central

    Dey, Nirmalya; Bera, Amit; Das, Falguni; Ghosh-Choudhury, Nandini; Kasinath, Balakuntalam S.; Choudhury, Goutam Ghosh

    2015-01-01

    High glucose milieu inhibits PTEN expression to activate Akt kinase and induces glomerular mesangial cell hypertrophy and matrix protein expression in diabetic nephropathy. Specific mechanism by which high glucose inhibits PTEN expression is not clear. We found that high glucose increased the expression of the microRNA-26a (miR-26a) in mesangial cells. Using a sensor plasmid with 3’UTR-driven luciferase, we showed PTEN as a target of miR-26a in response to high glucose. Overexpression of miR-26a reduced the PTEN protein levels resulting in increased Akt kinase activity similar to high glucose treatment. In contrast, anti-miR-26a reversed high glucose-induced suppression of PTEN with concomitant inhibition of Akt kinase activity. Akt-mediated phosphorylation of tuberin and PRAS40 regulates mTORC1, which is necessary for mesangial cell hypertrophy and matrix protein expression. Inhibition of high glucose-induced miR-26a blocked phosphorylation of tuberin and PRAS40, which lead to suppression of phosphorylation of S6 kinase and 4EBP-1, two substrates of mTORC1. Furthermore, we show that expression of miR-26a induced mesangial cell hypertrophy and increased fibronectin and collagen I (α2) expression similar to that observed with the cells incubated with high glucose. Anti-miR-26a inhibited these phenomena in response to high glucose. Together our results provide the first evidence for the involvement of miR-26a in high glucose-induced mesangial cell hypertrophy and matrix protein expression. These data indicate the potential therapeutic utility of anti-miR-26a for the complications of diabetic kidney disease. PMID:25797045

  12. Threshold-Voltage-Shift Compensation and Suppression Method Using Hydrogenated Amorphous Silicon Thin-Film Transistors for Large Active Matrix Organic Light-Emitting Diode Displays

    NASA Astrophysics Data System (ADS)

    Oh, Kyonghwan; Kwon, Oh-Kyong

    2012-03-01

    A threshold-voltage-shift compensation and suppression method for active matrix organic light-emitting diode (AMOLED) displays fabricated using a hydrogenated amorphous silicon thin-film transistor (TFT) backplane is proposed. The proposed method compensates for the threshold voltage variation of TFTs due to different threshold voltage shifts during emission time and extends the lifetime of the AMOLED panel. Measurement results show that the error range of emission current is from -1.1 to +1.7% when the threshold voltage of TFTs varies from 1.2 to 3.0 V.

  13. Preliminary evidence for a matrix metalloproteinase-2 (MMP-2)-dependent shedding of soluble CD40 ligand (sCD40L) from activated platelets.

    PubMed

    Reinboldt, Stephan; Wenzel, Folker; Rauch, Bernhard H; Hohlfeld, Thomas; Grandoch, Maria; Fischer, Jens W; Weber, Artur-Aron

    2009-09-01

    Platelets are the major source of soluble CD40 ligand (sCD40L) in the blood. It has been demonstrated that CD40L is cleaved from the surface of activated platelets to release sCD40L. However, the enzyme involved in sCD40L shedding has not been identified yet. Using a panel of pharmacological inhibitors of serine, cysteine, aspartate, or metalloproteinases, preliminary evidence is presented for the hypothesis that matrix metalloproteinase-2 (MMP-2) might be the protease, primarily responsible for CD40L cleavage from platelet surface. PMID:19811225

  14. High Glucose-Induced Oxidative Stress Mediates Apoptosis and Extracellular Matrix Metabolic Imbalances Possibly via p38 MAPK Activation in Rat Nucleus Pulposus Cells.

    PubMed

    Cheng, Xiaofei; Ni, Bin; Zhang, Feng; Hu, Ying; Zhao, Jie

    2016-01-01

    Objectives. To investigate whether high glucose-induced oxidative stress is implicated in apoptosis of rat nucleus pulposus cells (NPCs) and abnormal expression of critical genes involved in the metabolic balance of extracellular matrix (ECM). Methods. NPCs were cultured with various concentrations of glucose to detect cell viability and apoptosis. Cells cultured with high glucose (25 mM) were untreated or pretreated with N-acetylcysteine or a p38 MAPK inhibitor SB 202190. Reactive oxygen species (ROS) production was evaluated. Activation of p38 MAPK was measured by Western blot. The expression of ECM metabolism-related genes, including type II collagen, aggrecan, SRY-related high-mobility-group box 9 (Sox-9), matrix metalloproteinase 3 (MMP-3), and tissue inhibitor of metalloproteinase 1 (TIMP-1), was analyzed by semiquantitative RT-PCR. Results. High glucose reduced viability of NPCs and induced apoptosis. High glucose resulted in increased ROS generation and p38 MAPK activation. In addition, it negatively regulated the expression of type II collagen, aggrecan, Sox-9, and TIMP-1 and positively regulated MMP-3 expression. These results were changed by pretreatment with N-acetylcysteine or SB 202190. Conclusions. High glucose might promote apoptosis of NPCs, trigger ECM catabolic pathways, and inhibit its anabolic activities, possibly through a p38 MAPK-dependent oxidative stress mechanism. PMID:27635402

  15. High Glucose-Induced Oxidative Stress Mediates Apoptosis and Extracellular Matrix Metabolic Imbalances Possibly via p38 MAPK Activation in Rat Nucleus Pulposus Cells

    PubMed Central

    Cheng, Xiaofei; Ni, Bin; Zhang, Feng; Hu, Ying

    2016-01-01

    Objectives. To investigate whether high glucose-induced oxidative stress is implicated in apoptosis of rat nucleus pulposus cells (NPCs) and abnormal expression of critical genes involved in the metabolic balance of extracellular matrix (ECM). Methods. NPCs were cultured with various concentrations of glucose to detect cell viability and apoptosis. Cells cultured with high glucose (25 mM) were untreated or pretreated with N-acetylcysteine or a p38 MAPK inhibitor SB 202190. Reactive oxygen species (ROS) production was evaluated. Activation of p38 MAPK was measured by Western blot. The expression of ECM metabolism-related genes, including type II collagen, aggrecan, SRY-related high-mobility-group box 9 (Sox-9), matrix metalloproteinase 3 (MMP-3), and tissue inhibitor of metalloproteinase 1 (TIMP-1), was analyzed by semiquantitative RT-PCR. Results. High glucose reduced viability of NPCs and induced apoptosis. High glucose resulted in increased ROS generation and p38 MAPK activation. In addition, it negatively regulated the expression of type II collagen, aggrecan, Sox-9, and TIMP-1 and positively regulated MMP-3 expression. These results were changed by pretreatment with N-acetylcysteine or SB 202190. Conclusions. High glucose might promote apoptosis of NPCs, trigger ECM catabolic pathways, and inhibit its anabolic activities, possibly through a p38 MAPK-dependent oxidative stress mechanism.

  16. High Glucose-Induced Oxidative Stress Mediates Apoptosis and Extracellular Matrix Metabolic Imbalances Possibly via p38 MAPK Activation in Rat Nucleus Pulposus Cells

    PubMed Central

    Cheng, Xiaofei; Ni, Bin; Zhang, Feng; Hu, Ying

    2016-01-01

    Objectives. To investigate whether high glucose-induced oxidative stress is implicated in apoptosis of rat nucleus pulposus cells (NPCs) and abnormal expression of critical genes involved in the metabolic balance of extracellular matrix (ECM). Methods. NPCs were cultured with various concentrations of glucose to detect cell viability and apoptosis. Cells cultured with high glucose (25 mM) were untreated or pretreated with N-acetylcysteine or a p38 MAPK inhibitor SB 202190. Reactive oxygen species (ROS) production was evaluated. Activation of p38 MAPK was measured by Western blot. The expression of ECM metabolism-related genes, including type II collagen, aggrecan, SRY-related high-mobility-group box 9 (Sox-9), matrix metalloproteinase 3 (MMP-3), and tissue inhibitor of metalloproteinase 1 (TIMP-1), was analyzed by semiquantitative RT-PCR. Results. High glucose reduced viability of NPCs and induced apoptosis. High glucose resulted in increased ROS generation and p38 MAPK activation. In addition, it negatively regulated the expression of type II collagen, aggrecan, Sox-9, and TIMP-1 and positively regulated MMP-3 expression. These results were changed by pretreatment with N-acetylcysteine or SB 202190. Conclusions. High glucose might promote apoptosis of NPCs, trigger ECM catabolic pathways, and inhibit its anabolic activities, possibly through a p38 MAPK-dependent oxidative stress mechanism. PMID:27635402

  17. Co-Culture of Tumor Spheroids and Fibroblasts in a Collagen Matrix-Incorporated Microfluidic Chip Mimics Reciprocal Activation in Solid Tumor Microenvironment

    PubMed Central

    Jeong, Su-Yeong; Lee, Ji-Hyun; Shin, Yoojin; Chung, Seok; Kuh, Hyo-Jeong

    2016-01-01

    Multicellular 3D culture and interaction with stromal components are considered essential elements in establishing a ‘more clinically relevant’ tumor model. Matrix-embedded 3D cultures using a microfluidic chip platform can recapitulate the microscale interaction within tumor microenvironments. As a major component of tumor microenvironment, cancer-associated fibroblasts (CAFs) play a role in cancer progression and drug resistance. Here, we present a microfluidic chip-based tumor tissue culture model that integrates 3D tumor spheroids (TSs) with CAF in proximity within a hydrogel scaffold. HT-29 human colorectal carcinoma cells grew into 3D TSs and the growth was stimulated when co-cultured with fibroblasts as shown by 1.5-folds increase of % changes in diameter over 5 days. TS cultured for 6 days showed a reduced expression of Ki-67 along with increased expression of fibronectin when co-cultured with fibroblasts compared to mono-cultured TSs. Fibroblasts were activated under co-culture conditions, as demonstrated by increases in α-SMA expression and migratory activity. When exposed to paclitaxel, a survival advantage was observed in TSs co-cultured with activated fibroblasts. Overall, we demonstrated the reciprocal interaction between TSs and fibroblasts in our 7-channel microfluidic chip. The co-culture of 3D TS-CAF in a collagen matrix-incorporated microfluidic chip may be useful to study the tumor microenvironment and for evaluation of drug screening and evaluation. PMID:27391808

  18. Anti-elastase, anti-tyrosinase and matrix metalloproteinase-1 inhibitory activity of earthworm extracts as potential new anti-aging agent

    PubMed Central

    Azmi, Nurhazirah; Hashim, Puziah; Hashim, Dzulkifly M; Halimoon, Normala; Majid, Nik Muhamad Nik

    2014-01-01

    Objective To examine whether earthworms of Eisenia fetida, Lumbricus rubellus and Eudrilus eugeniae extracts have elastase, tyrosinase and matrix metalloproteinase-1 (MMP-1) inhibitory activity. Methods The earthworms extract was screened for elastase, tyrosinase and MMP-1 inhibitory activity and compared with the positive controls. It was also evaluated for whitening and anti-wrinkle capacity. Results The extract showed significantly (P<0.05) good elastase and tyrosinase inhibition and excellent MMP-1 inhibition compared to N-Isobutyl-N-(4-methoxyphenylsulfonyl)-glycylhydroxamic acid. Conclusions Earthworms extract showed effective inhibition of tyrosinase, elastase and MMP-1 activities. Therefore, this experiment further rationalizes the traditional use of this worm extracts which may be useful as an anti-wrinkle agent. PMID:25183109

  19. Decreased expression of the plasminogen activator inhibitor type 1 is involved in degradation of extracellular matrix surrounding cervical cancer stem cells.

    PubMed

    Sato, Masakazu; Kawana, Kei; Adachi, Katsuyuki; Fujimoto, Asaha; Yoshida, Mitsuyo; Nakamura, Hiroe; Nishida, Haruka; Inoue, Tomoko; Taguchi, Ayumi; Takahashi, Juri; Kojima, Satoko; Yamashita, Aki; Tomio, Kensuke; Nagamatsu, Takeshi; Wada-Hiraike, Osamu; Oda, Katsutoshi; Osuga, Yutaka; Fujii, Tomoyuki

    2016-02-01

    The plasminogen activator (PA) system consists of plasminogen activator inhibitor type 1 (PAI-1), urokinase-type plasminogen activator and its receptor (uPA and uPAR). PAI-1 inhibits the activation of uPA (which converts plasminogen to plasmin), and is involved in cancer invasion and metastasis, by remodeling the extracellular matrix (ECM) through regulating plasmin. Cancer stem cells (CSCs) are a small subset of cells within tumors, and are thought to be involved in tumor recurrence and metastasis. Considering these facts, we investigated the relationship between PAI-1 and cervical CSCs. We used ALDH1 as a marker of cervical CSCs. First, we demonstrated that culturing ALDH1-high cells and ALDH-low cells on collagen IV-coted plates increased their expression of active PAI-1 (ELISA), and these increases were suggested to be at mRNA expression levels (RT-qPCR). Secondly, we demonstrated PAI-1 was indeed involved in the ECM maintenance. With gelatin zymography assays, we found that ALDH1-high cells and ALDH-low cells expressed pro-matrix metalloproteinase-2 (pro-MMP-2) irrespective of their coatings. With gelatinase/collagenase assay kit, we confirmed that collagenase activity was increased when ALDH1-low cells were exposed to TM5275, a small molecule inhibitor of PAI-1. Putting the data together, we hypothesized that cancer cells adhered to basal membrane secrete abundant PAI-1, on the other hand, cancer cells (especially CSCs rather than non-CSCs) distant from basal membrane secrete less PAI-1, which makes the ECM surrounding CSCs more susceptible to degradation. Our study could be an explanation of conflicting reports, where some researchers found negative impacts of PAI-1 expression on clinical outcomes and others not, by considering the concept of CSCs.

  20. In-situ growth of antimony sulfide in carbon nanoparticle matrix: Enhanced electrocatalytic activity as counter electrode in dye-sensitized solar cells

    NASA Astrophysics Data System (ADS)

    Sun, Panpan; Zhang, Ming; Ai, Changzhi; Wu, Zhixin; Lu, Shuang; Zhang, Xintong; Huang, Niu; Sun, Yihua; Sun, Xiaohua

    2016-07-01

    Considering the undesirable electrocatalytic activity toward I-/I3- redox system of prinstine antimony sulfide (Sb2S3) fabricated with the existing conditions, a mesoporous carbon nanoparticle film (CNP) is introduced here for in-situ growth of Sb2S3 to construct a Sb2S3@CNP hybrid catalyst. Based on a Sb-thiourea precursor solution, in-situ growth of Sb2S3 can be achieved via solution deposition (denoted as Sb2S3@CNP-S) as well as atmospheric pressure thermal evaporation (denoted as Sb2S3@CNP-T) in CNP matrix. Structural characterizations indicate that Sb2S3 particles have well dispersed in the pores of CNP matrix. Because of the introduction of porous and conductive CNP matrix to support Sb2S3, the hybrid catalyst exhibits lower charge transfer resistance at the catalyst/electrolyte interface and higher electrocatalytic activity. When used as counter electrode (CE) for dye-sensitized solar cells (DSSCs), devices using Sb2S3@CNP hybrid catalyst as CE produce fill factor of 67.6% and 66.3%, which is significantly higher than that using pristine Sb2S3 fabricated in our previous work (52.8%). Finally, the corresponding power conversion efficiencies reach 6.69% (Sb2S3@CNP-S) and 6.24% (Sb2S3@CNP-T), respectively, which are comparable to that using Pt CE measured under the same conditions (6.74%).

  1. Readout of TPC Tracking Chambers with GEMs and Pixel Chip

    SciTech Connect

    Kadyk, John; Kim, T.; Freytsis, M.; Button-Shafer, J.; Kadyk, J.; Vahsen, S.E.; Wenzel, W.A.

    2007-12-21

    Two layers of GEMs and the ATLAS Pixel Chip, FEI3, have been combined and tested as a prototype for Time Projection Chamber (TPC) readout at the International Linear Collider (ILC). The double-layer GEM system amplifies charge with gain sufficient to detect all track ionization. The suitability of three gas mixtures for this application was investigated, and gain measurements are presented. A large sample of cosmic ray tracks was reconstructed in 3D by using the simultaneous timing and 2D spatial information from the pixel chip. The chip provides pixel charge measurement as well as timing. These results demonstrate that a double GEM and pixel combination, with a suitably modified pixel ASIC, could meet the stringent readout requirements of the ILC.

  2. Development of TORCH readout electronics for customised MCPs

    NASA Astrophysics Data System (ADS)

    Gao, R.; Brook, N.; Castillo García, L.; Cussans, D.; Fohl, K.; Forty, R.; Frei, C.; Gys, T.; Harnew, N.; Piedigrossi, D.; Rademacker, J.; Ros García, A.; Van Dijk, M.

    2016-04-01

    The TORCH detector is being developed for low-momentum particle identification, combining time-of-flight and Cherenkov techniques to achieve charged particle pi/K/p separation up to 10 GeV/c over a flight distance of 10m. This requires a timing resolution of 70 ps for single photons. Based on an existing scalable design, production and testing of a TORCH readout system has been undertaken over the past year, and a novel customized Micro Channel Plate (MCP) photomultiplier device with 128-channels has been instrumented. This paper will report on the development of the readout system which is being used to measure time-of-flight in a test-beam, and its performance. We will also discuss the communication and data alignment between the TORCH system and the TimePix3 telescope in order to provide track reconstruction.

  3. Fast Low-Cost Multiple Sensor Readout System

    DOEpatents

    Carter-Lewis, David; Krennich, Frank; Le Bohec, Stephane; Petry, Dirk; Sleege, Gary

    2004-04-06

    A low resolution data acquisition system is presented. The data acquisition system has a plurality of readout modules serially connected to a controller. Each readout module has a FPGA in communication with analog to digital (A/D) converters, which are connected to sensors. The A/D converter has eight bit or lower resolution. The FPGA detects when a command is addressed to it and commands the A/D converters to convert analog sensor data into digital data. The digital data is sent on a high speed serial communication bus to the controller. A graphical display is used in one embodiment to indicate if a sensor reading is outside of a predetermined range.

  4. Readout of relaxation rates by nonadiabatic pumping spectroscopy

    NASA Astrophysics Data System (ADS)

    Riwar, Roman-Pascal; Roche, Benoît; Jehl, Xavier; Splettstoesser, Janine

    2016-06-01

    We put forward nonadiabatic charge pumping as a method for accessing the different charge relaxation rates as well as the relaxation rates of excited orbital states in double-quantum-dot setups, based on extremely size-limited quantum dots and dopant systems. The rates are obtained in a well-separated manner from plateaus, occurring when comparing the steady-state current for reversed driving cycles. This yields a reliable readout independent of any fitting parameters. Importantly, the nonadiabatic pumping spectroscopy essentially exploits the same driving scheme that the operation of these devices generally employs. We provide a detailed analysis of the working principle of the readout scheme as well as of possible errors, thereby demonstrating its broad applicability. The precise knowledge of relaxation rates is highly relevant for the implementation of time-dependently operated devices, such as electron pumps for metrology or qubits in quantum information.

  5. Implementation of the Timepix ASIC in the Scalable Readout System

    NASA Astrophysics Data System (ADS)

    Lupberger, M.; Desch, K.; Kaminski, J.

    2016-09-01

    We report on the development of electronics hardware, FPGA firmware and software to provide a flexible multi-chip readout of the Timepix ASIC within the framework of the Scalable Readout System (SRS). The system features FPGA-based zero-suppression and the possibility to read out up to 4×8 chips with a single Front End Concentrator (FEC). By operating several FECs in parallel, in principle an arbitrary number of chips can be read out, exploiting the scaling features of SRS. Specifically, we tested the system with a setup consisting of 160 Timepix ASICs, operated as GridPix devices in a large TPC field cage in a 1 T magnetic field at a DESY test beam facility providing an electron beam of up to 6 GeV. We discuss the design choices, the dedicated hardware components, the FPGA firmware as well as the performance of the system in the test beam.

  6. Abnormal activation of calpain and protein kinase Cα promotes a constitutive release of matrix metalloproteinase 9 in peripheral blood mononuclear cells from cystic fibrosis patients.

    PubMed

    Averna, Monica; Bavestrello, Margherita; Cresta, Federico; Pedrazzi, Marco; De Tullio, Roberta; Minicucci, Laura; Sparatore, Bianca; Salamino, Franca; Pontremoli, Sandro; Melloni, Edon

    2016-08-15

    Matrix metalloproteinase 9 (MMP9) is physiologically involved in remodeling the extracellular matrix components but its abnormal release has been observed in several human pathologies. We here report that peripheral blood mononuclear cells (PBMCs), isolated from cystic fibrosis (CF) patients homozygous for F508del-cystic fibrosis transmembrane conductance regulator (CFTR), express constitutively and release at high rate MMP9 due to the alteration in their intracellular Ca(2+) homeostasis. This spontaneous and sustained MMP9 secretion may contribute to the accumulation of this protease in fluids of CF patients. Conversely, in PBMCs isolated from healthy donors, expression and secretion of MMP9 are undetectable but can be evoked, after 12 h of culture, by paracrine stimulation which also promotes an increase in [Ca(2+)]i. We also demonstrate that in both CF and control PBMCs the Ca(2+)-dependent MMP9 secretion is mediated by the concomitant activation of calpain and protein kinase Cα (PKCα), and that MMP9 expression involves extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) phosphorylation. Our results are supported by the fact that either the inhibition of Ca(2+) entry or chelation of [Ca(2+)]i as well as the inhibition of single components of the signaling pathway or the restoration of CFTR activity all promote the reduction of MMP9 secretion. PMID:27349634

  7. Dickkopf-3 regulates prostate epithelial cell acinar morphogenesis and prostate cancer cell invasion by limiting TGF-β-dependent activation of matrix metalloproteases.

    PubMed

    Romero, Diana; Al-Shareef, Zainab; Gorroño-Etxebarria, Irantzu; Atkins, Stephanie; Turrell, Frances; Chhetri, Jyoti; Bengoa-Vergniory, Nora; Zenzmaier, Christoph; Berger, Peter; Waxman, Jonathan; Kypta, Robert

    2016-01-01

    Dickkopf-3 (Dkk-3) is a secreted protein whose expression is downregulated in many types of cancer. Endogenous Dkk-3 is required for formation of acini in 3D cultures of prostate epithelial cells, where it inhibits transforming growth factor (TGF)-β/Smad signaling. Here, we examined the effects of Dkk-3 on the expression and activity of matrix metalloproteases (MMPs), which mediate the effects of TGF-β on extracellular matrix disassembly during tissue morphogenesis and promote invasion of tumor cells. Silencing of Dkk-3 in prostate epithelial cells resulted in increased expression and enzyme activity of MMP-2 and MMP-9. Inhibition of MMP-9 partially restored normal acinar morphogenesis in Dkk-3-silenced RWPE-1 prostate epithelial cells. In PC3 prostate cancer cells, Dkk-3 inhibited TGF-β-dependent migration and invasion. Inhibition was mediated by the Dkk-3 C-terminal cysteine-rich domain (Cys2), which also inhibited TGF-β-induced expression of MMP9 and MMP13. In contrast, Dkk-3, but not Cys2, increased formation of normal acini in Dkk-3-silenced prostate epithelial cells. These observations highlight a role for Dkk-3 in modulating TGF-β/MMP signals in the prostate, and suggest that the Dkk-3 Cys2 domain can be used as a basis for therapies that target the tumor promoting effects of TGF-β signaling in advanced prostate cancer.

  8. Plastic substrates for active matrix liquid crystal display incapable of withstanding processing temperature of over 200 C and method of fabrication

    DOEpatents

    Carey, P.G.; Smith, P.M.; Havens, J.H.; Jones, P.

    1999-01-05

    Bright-polarizer-free, active-matrix liquid crystal displays (AMLCDs) are formed on plastic substrates. The primary components of the display are a pixel circuit fabricated on one plastic substrate, an intervening liquid-crystal material, and a counter electrode on a second plastic substrate. The-pixel circuit contains one or more thin-film transistors (TFTs) and either a transparent or reflective pixel electrode manufactured at sufficiently low temperatures to avoid damage to the plastic substrate. Fabrication of the TFTs can be carried out at temperatures less than 100 C. The liquid crystal material is a commercially made nematic curvilinear aligned phase (NCAP) film. The counter electrode is comprised of a plastic substrate coated with a transparent conductor, such as indium-doped tin oxide (ITO). By coupling the active matrix with NCAP, a high-information content can be provided in a bright, fully plastic package. Applications include any low cost portable electronics containing flat displays where ruggedization of the display is desired. 12 figs.

  9. Plastic substrates for active matrix liquid crystal display incapable of withstanding processing temperature of over 200.degree. C and method of fabrication

    DOEpatents

    Carey, Paul G.; Smith, Patrick M.; Havens, John; Jones, Phil

    1999-01-01

    Bright-polarizer-free, active-matrix liquid crystal displays (AMLCDs) are formed on plastic substrates. The primary components of the display are a pixel circuit fabricated on one plastic substrate, an intervening liquid-crystal material, and a counter electrode on a second plastic substrate. The-pixel circuit contains one or more thin-film transistors (TFTs) and either a transparent or reflective pixel electrode manufactured at sufficiently low temperatures to avoid damage to the plastic substrate. Fabrication of the TFTs can be carried out at temperatures less than 100.degree. C. The liquid crystal material is a commercially made nematic curvilinear aligned phase (NCAP) film. The counter electrode is comprised of a plastic substrate coated with a transparent conductor, such as indium-doped tin oxide (ITO). By coupling the active matrix with NCAP, a high-information content can be provided in a bright, fully plastic package. Applications include any low cost portable electronics containing flat displays where ruggedization of the display is desired.

  10. Inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2

    SciTech Connect

    Peng, P.-L.; Hsieh, Y.-S.; Wang, C.-J.; Hsu, J.-L.; Chou, F.-P. . E-mail: fpchou@csmu.edu.tw

    2006-07-01

    Berberine, a compound isolated from medicinal herbs, has been reported with many pharmacological effects related to anti-cancer and anti-inflammation capabilities. In this study, we observed that berberine exerted a dose- and time-dependent inhibitory effect on the motility and invasion ability of a highly metastatic A549 cells under non-cytotoxic concentrations. In cancer cell migration and invasion process, matrix-degrading proteinases are required. A549 cell treated with berberine at various concentrations showed reduced ECM proteinases including matrix metalloproteinase-2 (MMP2) and urokinase-plasminogen activator (u-PA) by gelatin and casein zymography analysis. The inhibitory effect is likely to be at the transcriptional level, since the reduction in the transcripts levels was corresponding to the proteins. Moreover, berberine also exerted its action via regulating tissue inhibitor of metalloproteinase-2 (TIMP-2) and urokinase-plasminogen activator inhibitor (PAI). The upstream mediators of the effect involved c-jun, c-fos and NF-{kappa}B, as evidenced by reduced phosphorylation of the proteins. These findings suggest that berberine possesses an anti-metastatic effect in non-small lung cancer cell and may, therefore, be helpful in clinical treatment.

  11. DETECTORS AND EXPERIMENTAL METHODS: Design and test of a Multi-gap Resistive Plate Chamber with Long readout-strip (LMRPC)

    NASA Astrophysics Data System (ADS)

    Sun, Yong-Jie; Li, Cheng; Zhou, Yi; Shao, Ming; Zhao, Yan-E.; Chen, Hong-Fang

    2009-02-01

    A new kind (two end readout) of Multi-gap Resistive Plate Chamber with long readout-strip (LMRPC) is developed to be used at the large-area Muon Telescope Detector (MTD) at mid-rapidity at RHIC/STAR experiment for Time-of-Flight (TOF) measurement. The LMRPC has an active area of 87 cm × 17 cm, 10 gas gaps of 250 μm arranged in 2 stacks, with readout strips of 2.5 cm wide and 90 cm long. The considerations in LMRPC design related to its performance are discussed in this paper. The cosmic ray test results of a prototype LMRPC show a detection efficiency >95% and the time resolution ~70 ps.

  12. High fidelity readout of a single electron spin

    NASA Astrophysics Data System (ADS)

    Keselman, Anna; Glickman, Yinnon; Akerman, Nitzan; Kotler, Shlomi; Dallal, Yehonatan; Ozeri, Roee

    2010-03-01

    We use the two spin states of the valence electron of a single trapped ^88Sr^+ ion as a physical qubit implementation. For qubit readout one of the qubit states is shelved to a metastable D level using a narrow linewidth 674nm diode laser followed by state-selective fluorescence detection. Careful analysis of the resulting photon detection statistics allows for a minimal detection error of 2 . 10-3, compatible with recent estimates of the fault-tolerance required error threshold.

  13. Readout of silicon strip detectors with position and timing information

    NASA Astrophysics Data System (ADS)

    Friedl, M.; Irmler, C.; Pernicka, M.

    2009-01-01

    Low-noise front-end amplifiers for silicon strip detectors are already available for decades, providing excellent signal-to-noise ratio and thus very precise spatial resolution, but at the cost of a long shaping time in the microsecond range. Due to occupancy and pile-up issues, modern experiments need much faster electronics. With submicron ASICs, adequate readout and data processing, it is possible to obtain not only spatial hit data, but also accurate timing information—a feature which is rarely exploited so far. We present the concept of a silicon vertex detector readout system intended for an upgrade of the Belle experiment at KEK (Tsukuba, Japan). The APV25 front-end chip, originally developed for CMS at CERN, is used in a way where it delivers multiple samples along the shaped waveform, such that not only the analog pulse height, but also the timing of each particle hit can be determined. We developed a complete readout system including an FADC +Processor VME module which performs zero-suppression in FPGAs. The hit time measurement is also planned on the same module. As fast amplifiers are inherently more susceptible to noise, which largely depends on the load capacitance, the front-end chips should be located as close to the detector as possible. On the other hand, the material budget, especially in a low-energy electron-positron machine such as Belle, should be minimized. We tried to merge those demands with a fully functional "Flex_Module", where thinned APV25 readout chips are mounted on the silicon sensor.

  14. Evaluation of an Integrated Read-Out Layer Prototype

    SciTech Connect

    Abu-Ajamieh, Fayez; /NIU

    2011-08-18

    This thesis presents evaluation results of an Integrated Read-out Layer (IRL), a proposed concept in scintillator-based calorimetry intended to meet the exceptional calorimetric requirements of the envisaged International Linear Collider (ILC). This study presents a full characterization of the prototype IRL, including exploration of relevant parameters, calibration performance, and the uniformity of response. The study represents proof of the IRL concept. Finally, proposed design enhancements are presented.

  15. 3D, Flash, Induced Current Readout for Silicon Sensors

    SciTech Connect

    Parker, Sherwood I.

    2014-06-07

    A new method for silicon microstrip and pixel detector readout using (1) 65 nm-technology current amplifers which can, for the first time with silicon microstrop and pixel detectors, have response times far shorter than the charge collection time (2) 3D trench electrodes large enough to subtend a reasonable solid angle at most track locations and so have adequate sensitivity over a substantial volume of pixel, (3) induced signals in addition to, or in place of, collected charge

  16. A pixel unit-cell targeting 16 ns resolution and radiation hardness in a column read-out particle vertex detector

    SciTech Connect

    Wright, M.; Millaud, J.; Nygren, D.

    1992-10-01

    A pixel unit cell (PUC) circuit architecture, optimized for a column read out architecture, is reported. Each PUC contains an integrator, active filter, comparator, and optional analog store. The time-over-threshold (TOT) discriminator allows an all-digital interface to the array periphery readout while passing an analog measure of collected charge. Use of (existing) radiation hard processes, to build a detector bump-bonded to a pixel readout array, is targeted. Here, emphasis is on a qualitative explanation of how the unique circuit implementation benefits operation for Super Collider (SSC) detector application.

  17. ADVANCED READOUT ELECTRONICS FOR MULTIELEMENT CdZnTe SENSORS.

    SciTech Connect

    DE GERONIMO,G.; O CONNOR,P.; KANDASAMY,A.; GROSHOLZ,J.

    2002-07-08

    A generation of high performance front-end and read-out ASICs customized for highly segmented CdZnTe sensors is presented. The ASICs, developed in a multi-year effort at Brookhaven National Laboratory, are targeted to a wide range of applications including medical, safeguards/security, industrial, research, and spectroscopy. The front-end multichannel ASICs provide high accuracy low noise preamplification and filtering of signals, with versions for small and large area CdZnTe elements. They implement a high order unipolar or bipolar shaper, an innovative low noise continuous reset system with self-adapting capability to the wide range of detector leakage currents, a new system for stabilizing the output baseline and high output driving capability. The general-purpose versions include programmable gain and peaking time. The read-out multichannel ASICs provide fully data driven high accuracy amplitude and time measurements, multiplexing and time domain derandomization of the shaped pulses. They implement a fast arbitration scheme and an array of innovative two-phase offset-free rail-to-rail analog peak detectors for buffering and absorption of input rate fluctuations, thus greatly relaxing the rate requirement on the external ADC. Pulse amplitude, hit timing, pulse risetime, and channel address per processed pulse are available at the output in correspondence of an external readout request. Prototype chips have been fabricated in 0.5 and 0.35 {micro}m CMOS and tested. Design concepts and experimental results are discussed.

  18. Demonstration of Time Domain Multiplexed Readout for Magnetically Coupled Calorimeters

    NASA Technical Reports Server (NTRS)

    Porst, J.-P.; Adams, J. S.; Balvin, M.; Bandler, S.; Beyer, J.; Busch, S. E.; Drung, D.; Seidel, G. M.; Smith, S. J.; Stevenson, T. R.

    2012-01-01

    Magnetically coupled calorimeters (MCC) have extremely high potential for x-ray applications due to the inherent high energy resolution capability and being non-dissipative. Although very high energy-resolution has been demonstrated, until now there has been no demonstration of multiplexed read-out. We report on the first realization of a time domain multiplexed (TDM) read-out. While this has many similarities with TDM of transition-edge-sensors (TES), for MGGs the energy resolution is limited by the SQUID read-out noise and requires the well established scheme to be altered in order to minimize degradation due to noise aliasing effects. In cur approach, each pixel is read out by a single first stage SQUID (SQ1) that is operated in open loop. The outputs of the SQ1 s are low-pass filtered with an array of low cross-talk inductors, then fed into a single-stage SQUID TD multiplexer. The multiplexer is addressed from room temperature and read out through a single amplifier channel. We present results achieved with a new detector platform. Noise performance is presented and compared to expectations. We have demonstrated multiplexed X-ray spectroscopy at 5.9keV with delta_FWHM=10eV. In an optimized setup, we show it is possible to multiplex 32 detectors without significantly degrading the Intrinsic detector resolution.

  19. An integrated wire harp and readout electronics inside vacuum

    SciTech Connect

    Chatterjee, Mou; Nabhiraj, P. Y.

    2015-03-15

    A wire harp is a well known instrument used in ion beam profile measurement and beam diagnostics. Till date, for beam instrumentation, the harp is placed inside the vacuum chamber or beam line in direct exposure to the beam profile to be measured, whereas the related readout electronics is placed outside somewhere at a convenient place. Here, a harp has been developed along with the readout electronics as an integrated part of it and both were placed inside the beam line vacuum (order of 10{sup −7} Torr) to make the system much simpler, easy to operate, and measure small beam current more accurately. The entire signal conversion and processing is done inside the vacuum unlike other systems; hence, the electronics is kept inside. This results in a lesser number (only 4 pin) of electrical connections (feedthrough) including power which otherwise would have required 32 feedthrough pins only for signal readout for a 13 × 13 (X × Y) channel harp. This paper describes a completely new approach to the design of a conventional beam harp widely used for beam instrumentation.

  20. Characterization results of the JUNGFRAU full scale readout ASIC

    NASA Astrophysics Data System (ADS)

    Mozzanica, A.; Bergamaschi, A.; Brueckner, M.; Cartier, S.; Dinapoli, R.; Greiffenberg, D.; Jungmann-Smith, J.; Maliakal, D.; Mezza, D.; Ramilli, M.; Ruder, C.; Schaedler, L.; Schmitt, B.; Shi, X.; Tinti, G.

    2016-02-01

    The two-dimensional pixel detector JUNGFRAU is designed for high performance photon science applications at free electron lasers and synchrotron light sources. It is developed for the SwissFEL currently under construction at the Paul Scherrer Institut, Switzerland. The detector is a hybrid pixel detector with a charge integration readout ASIC characterized by single photon sensitivity and a low noise performance over a dynamic range of 104 12 keV photons. Geometrically, a JUNGFRAU readout chip consists of 256×256 pixels of 75×75 μm2. The chips are bump bonded to 320 μm thick silicon sensors. Arrays of 2×4 chips are tiled to form modules of 4×8 cm2 area. Several multi-module systems with up to 16 Mpixels per system will be delivered to the two end stations at SwissFEL. The JUNGFRAU full scale readout ASIC and module design are presented along with characterization results of the first systems. Experiments from fluorescence X-ray, visible light illumination, and synchrotron irradiation are shown. The results include an electronic noise of ~50 electrons r.m.s., which enables single photon detection energies below 2 keV and a noise well below the Poisson statistical limit over the entire dynamic range. First imaging experiments are also shown.

  1. Improved Signal Chains for Readout of CMOS Imagers

    NASA Technical Reports Server (NTRS)

    Pain, Bedabrata; Hancock, Bruce; Cunningham, Thomas

    2009-01-01

    An improved generic design has been devised for implementing signal chains involved in readout from complementary metal oxide/semiconductor (CMOS) image sensors and for other readout integrated circuits (ICs) that perform equivalent functions. The design applies to any such IC in which output signal charges from the pixels in a given row are transferred simultaneously into sampling capacitors at the bottoms of the columns, then voltages representing individual pixel charges are read out in sequence by sequentially turning on column-selecting field-effect transistors (FETs) in synchronism with source-follower- or operational-amplifier-based amplifier circuits. The improved design affords the best features of prior source-follower-and operational- amplifier-based designs while overcoming the major limitations of those designs. The limitations can be summarized as follows: a) For a source-follower-based signal chain, the ohmic voltage drop associated with DC bias current flowing through the column-selection FET causes unacceptable voltage offset, nonlinearity, and reduced small-signal gain. b) For an operational-amplifier-based signal chain, the required bias current and the output noise increase superlinearly with size of the pixel array because of a corresponding increase in the effective capacitance of the row bus used to couple the sampled column charges to the operational amplifier. The effect of the bus capacitance is to simultaneously slow down the readout circuit and increase noise through the Miller effect.

  2. rf-SQUID qubit readout using a fast flux pulse

    NASA Astrophysics Data System (ADS)

    Bennett, Douglas A.; Longobardi, Luigi; Patel, Vijay; Chen, Wei; Lukens, James E.

    2007-11-01

    We report on development of a set-up for measuring intrawell dynamics in a Nb-based rf-SQUID qubit described by a double well potential, by rapidly tilting the potential, allowing escape to the adjacent well with high probability for an excited state but low probability for the ground state. The rapid tilt of the double well potential is accomplished via a readout flux pulse inductively coupled to the qubit from a microstrip transmission line on a separate chip suspended above the qubit chip. The readout pulse is analogous to the current bias pulse used to readout phase qubits and hysteretic dc-SQUID magnetometers. The coupling between the transmission line and the qubit is carefully controlled via a window in the ground plane between the signal conductor of the microstrip and the qubit loop. Since the high frequency transmission lines are on a separate chip, they can be independently characterized and reused for different qubit samples. Clean flux pulses as short as 5 ns with rise times of 0.5 ns have been coupled to the qubit to measure escape rates higher than 108 s-1, the lifetime of the excited state, and coherent oscillations between the ground and excited states within the same well.

  3. An integrated wire harp and readout electronics inside vacuum

    NASA Astrophysics Data System (ADS)

    Chatterjee, Mou; Nabhiraj, P. Y.

    2015-03-01

    A wire harp is a well known instrument used in ion beam profile measurement and beam diagnostics. Till date, for beam instrumentation, the harp is placed inside the vacuum chamber or beam line in direct exposure to the beam profile to be measured, whereas the related readout electronics is placed outside somewhere at a convenient place. Here, a harp has been developed along with the readout electronics as an integrated part of it and both were placed inside the beam line vacuum (order of 10-7 Torr) to make the system much simpler, easy to operate, and measure small beam current more accurately. The entire signal conversion and processing is done inside the vacuum unlike other systems; hence, the electronics is kept inside. This results in a lesser number (only 4 pin) of electrical connections (feedthrough) including power which otherwise would have required 32 feedthrough pins only for signal readout for a 13 × 13 (X × Y) channel harp. This paper describes a completely new approach to the design of a conventional beam harp widely used for beam instrumentation.

  4. An integrated wire harp and readout electronics inside vacuum.

    PubMed

    Chatterjee, Mou; Nabhiraj, P Y

    2015-03-01

    A wire harp is a well known instrument used in ion beam profile measurement and beam diagnostics. Till date, for beam instrumentation, the harp is placed inside the vacuum chamber or beam line in direct exposure to the beam profile to be measured, whereas the related readout electronics is placed outside somewhere at a convenient place. Here, a harp has been developed along with the readout electronics as an integrated part of it and both were placed inside the beam line vacuum (order of 10(-7) Torr) to make the system much simpler, easy to operate, and measure small beam current more accurately. The entire signal conversion and processing is done inside the vacuum unlike other systems; hence, the electronics is kept inside. This results in a lesser number (only 4 pin) of electrical connections (feedthrough) including power which otherwise would have required 32 feedthrough pins only for signal readout for a 13 × 13 (X × Y) channel harp. This paper describes a completely new approach to the design of a conventional beam harp widely used for beam instrumentation. PMID:25832261

  5. An integrated wire harp and readout electronics inside vacuum.

    PubMed

    Chatterjee, Mou; Nabhiraj, P Y

    2015-03-01

    A wire harp is a well known instrument used in ion beam profile measurement and beam diagnostics. Till date, for beam instrumentation, the harp is placed inside the vacuum chamber or beam line in direct exposure to the beam profile to be measured, whereas the related readout electronics is placed outside somewhere at a convenient place. Here, a harp has been developed along with the readout electronics as an integrated part of it and both were placed inside the beam line vacuum (order of 10(-7) Torr) to make the system much simpler, easy to operate, and measure small beam current more accurately. The entire signal conversion and processing is done inside the vacuum unlike other systems; hence, the electronics is kept inside. This results in a lesser number (only 4 pin) of electrical connections (feedthrough) including power which otherwise would have required 32 feedthrough pins only for signal readout for a 13 × 13 (X × Y) channel harp. This paper describes a completely new approach to the design of a conventional beam harp widely used for beam instrumentation.

  6. A cylindrical SPECT camera with de-centralized readout scheme

    NASA Astrophysics Data System (ADS)

    Habte, F.; Stenström, P.; Rillbert, A.; Bousselham, A.; Bohm, C.; Larsson, S. A.

    2001-09-01

    An optimized brain single photon emission computed tomograph (SPECT) camera is being designed at Stockholm University and Karolinska Hospital. The design goal is to achieve high sensitivity, high-count rate and high spatial resolution. The sensitivity is achieved by using a cylindrical crystal, which gives a closed geometry with large solid angles. A de-centralized readout scheme where only a local environment around the light excitation is readout supports high-count rates. The high resolution is achieved by using an optimized crystal configuration. A 12 mm crystal plus 12 mm light guide combination gave an intrinsic spatial resolution better than 3.5 mm (140 keV) in a prototype system. Simulations show that a modified configuration can improve this value. A cylindrical configuration with a rotating collimator significantly simplifies the mechanical design of the gantry. The data acquisition and control system uses early digitization and subsequent digital signal processing to extract timing and amplitude information, and monitors the position of the collimator. The readout system consists of 12 or more modules each based on programmable logic and a digital signal processor. The modules send data to a PC file server-reconstruction engine via a Firewire (IEEE-1394) network.

  7. Phospholipase C{gamma}1 stimulates transcriptional activation of the matrix metalloproteinase-3 gene via the protein kinase C/Raf/ERK cascade

    SciTech Connect

    Shin, Soon Young; Choi, Ha Young; Ahn, Bong-Hyun; Son, Sang Wook; Lee, Young Han . E-mail: younghan@hanyang.ac.kr

    2007-02-16

    The phospholipid hydrolase phospholipase C{gamma}1 (PLC{gamma}1) plays a major role in regulation of cell proliferation, development, and cell motility. Overexpression of PLC{gamma}1 is associated with tumor development, and it is overexpressed in some tumors. Matrix metalloproteinase-3 (MMP-3) is a protein involved in tumor invasion and metastasis. Here, we demonstrate that overexpression of PLC{gamma}1 stimulates MMP-3 expression at the transcriptional level via the PKC-mediated Raf/MEK1/ERK signaling cascade. We propose that modulation of PLC{gamma}1 activity might be of value in controlling the activity of MMPs, which are important regulators of invasion and metastasis in malignant tumors.

  8. (60)Co in cast steel matrix: A European interlaboratory comparison for the characterisation of new activity standards for calibration of gamma-ray spectrometers in metallurgy.

    PubMed

    Tzika, Faidra; Burda, Oleksiy; Hult, Mikael; Arnold, Dirk; Marroyo, Belén Caro; Dryák, Pavel; Fazio, Aldo; Ferreux, Laurent; García-Toraño, Eduardo; Javornik, Andrej; Klemola, Seppo; Luca, Aurelian; Moser, Hannah; Nečemer, Marijan; Peyrés, Virginia; Reis, Mario; Silva, Lidia; Šolc, Jaroslav; Svec, Anton; Tyminski, Zbigniew; Vodenik, Branko; Wätjen, Uwe

    2016-08-01

    Two series of activity standards of (60)Co in cast steel matrix, developed for the calibration of gamma-ray spectrometry systems in the metallurgical sector, were characterised using a European interlaboratory comparison among twelve National Metrology Institutes and one international organisation. The first standard, consisting of 14 disc shaped samples, was cast from steel contaminated during production ("originally"), and the second, consisting of 15 similar discs, from artificially-contaminated ("spiked") steel. The reference activity concentrations of (60)Co in the cast steel standards were (1.077±0.019) Bqg(-1) on 1 January 2013 12h00 UT and (1.483±0.022) Bqg(-1) on 1 June 2013 12h00 UT, respectively.

  9. Identification of Proteins with Potential Osteogenic Activity Present in the Water-Soluble Matrix Proteins from Crassostrea gigas Nacre Using a Proteomic Approach

    PubMed Central

    Oliveira, Daniel V.; Silva, Tomé S.; Cordeiro, Odete D.; Cavaco, Sofia I.; Simes, Dina C.

    2012-01-01

    Nacre, when implanted in vivo in bones of dogs, sheep, mice, and humans, induces a biological response that includes integration and osteogenic activity on the host tissue that seems to be activated by a set of proteins present in the nacre water-soluble matrix (WSM). We describe here an experimental approach that can accurately identify the proteins present in the WSM of shell mollusk nacre. Four proteins (three gigasin-2 isoforms and a cystatin A2) were for the first time identified in WSM of Crassostrea gigas nacre using 2DE and LC-MS/MS for protein identification. These proteins are thought to be involved in bone remodeling processes and could be responsible for the biocompatibility shown between bone and nacre grafts. These results represent a contribution to the study of shell biomineralization process and opens new perspectives for the development of new nacre biomaterials for orthopedic applications. PMID:22666151

  10. (60)Co in cast steel matrix: A European interlaboratory comparison for the characterisation of new activity standards for calibration of gamma-ray spectrometers in metallurgy.

    PubMed

    Tzika, Faidra; Burda, Oleksiy; Hult, Mikael; Arnold, Dirk; Marroyo, Belén Caro; Dryák, Pavel; Fazio, Aldo; Ferreux, Laurent; García-Toraño, Eduardo; Javornik, Andrej; Klemola, Seppo; Luca, Aurelian; Moser, Hannah; Nečemer, Marijan; Peyrés, Virginia; Reis, Mario; Silva, Lidia; Šolc, Jaroslav; Svec, Anton; Tyminski, Zbigniew; Vodenik, Branko; Wätjen, Uwe

    2016-08-01

    Two series of activity standards of (60)Co in cast steel matrix, developed for the calibration of gamma-ray spectrometry systems in the metallurgical sector, were characterised using a European interlaboratory comparison among twelve National Metrology Institutes and one international organisation. The first standard, consisting of 14 disc shaped samples, was cast from steel contaminated during production ("originally"), and the second, consisting of 15 similar discs, from artificially-contaminated ("spiked") steel. The reference activity concentrations of (60)Co in the cast steel standards were (1.077±0.019) Bqg(-1) on 1 January 2013 12h00 UT and (1.483±0.022) Bqg(-1) on 1 June 2013 12h00 UT, respectively. PMID:27236833

  11. Suppression of activation energy and superconductivity by the addition of Al{sub 2}O{sub 3} nanoparticles in CuTl-1223 matrix

    SciTech Connect

    Jabbar, Abdul; Qasim, Irfan; Mumtaz, M.; Zubair, M.; Nadeem, K.; Khurram, A. A.

    2014-05-28

    Low anisotropic (Cu{sub 0.5}Tl{sub 0.5})Ba{sub 2}Ca{sub 2}Cu{sub 3}O{sub 10−δ} (CuTl-1223) high T{sub c} superconducting matrix was synthesized by solid-state reaction and Al{sub 2}O{sub 3} nanoparticles were prepared separately by co-precipitation method. Al{sub 2}O{sub 3} nanoparticles were added with different concentrations during the final sintering cycle of CuTl-1223 superconducting matrix to get the required (Al{sub 2}O{sub 3}){sub y}/CuTl-1223, y = 0.0, 0.5, 0.7, 1.0, and 1.5 wt. %, composites. The samples were characterized by X-ray diffraction (XRD), scanning electron microscopy, energy dispersive X-ray, and dc-resistivity (ρ) measurements. The activation energy and superconductivity were suppressed with increasing concentration of Al{sub 2}O{sub 3} nanoparticles in (CuTl-1223) matrix. The XRD analysis showed that the addition of Al{sub 2}O{sub 3} nanoparticles did not affect the crystal structure of the parent CuTl-1223 superconducting phase. The suppression of activation energy and superconducting properties is most probably due to weak flux pinning in the samples. The possible reason of weak flux pinning is reduction of weak links and enhanced inter-grain coupling due to the presence of Al{sub 2}O{sub 3} nanoparticles at the grain boundaries. The presence of Al{sub 2}O{sub 3} nanoparticles at the grain boundaries possibly reduced the number of flux pinning centers, which were present in the form of weak links in the pure CuTl-1223 superconducting matrix. The increase in the values of inter-grain coupling (α) deduced from the fluctuation induced conductivity analysis with the increased concentration of Al{sub 2}O{sub 3} nanoparticles is a theoretical evidence of improved inter-grain coupling.

  12. Calcium Alginate Gels as Stem Cell Matrix – Making Paracrine Stem Cell Activity Available for Enhanced Healing after Surgery

    PubMed Central

    Schmitt, Andreas; Rödel, Philipp; Anamur, Cihad; Seeliger, Claudine; Imhoff, Andreas B.; Herbst, Elmar; Vogt, Stephan; van Griensven, Martijn; Winter, Gerhard; Engert, Julia

    2015-01-01

    Regeneration after surgery can be improved by the administration of anabolic growth factors. However, to locally maintain these factors at the site of regeneration is problematic. The aim of this study was to develop a matrix system containing human mesenchymal stem cells (MSCs) which can be applied to the surgical site and allows the secretion of endogenous healing factors from the cells. Calcium alginate gels were prepared by a combination of internal and external gelation. The gelling behaviour, mechanical stability, surface adhesive properties and injectability of the gels were investigated. The permeability of the gels for growth factors was analysed using bovine serum albumin and lysozyme as model proteins. Human MSCs were isolated, cultivated and seeded into the alginate gels. Cell viability was determined by AlamarBlue assay and fluorescence microscopy. The release of human VEGF and bFGF from the cells was determined using an enzyme-linked immunoassay. Gels with sufficient mechanical properties were prepared which remained injectable through a syringe and solidified in a sufficient time frame after application. Surface adhesion was improved by the addition of polyethylene glycol 300,000 and hyaluronic acid. Humans MSCs remained viable for the duration of 6 weeks within the gels. Human VEGF and bFGF was found in quantifiable concentrations in cell culture supernatants of gels loaded with MSCs and incubated for a period of 6 weeks. This work shows that calcium alginate gels can function as immobilization matrices for human MSCs. PMID:25793885

  13. A composite demineralized bone matrix--self assembling peptide scaffold for enhancing cell and growth factor activity in bone marrow.

    PubMed

    Hou, Tianyong; Li, Zhiqiang; Luo, Fei; Xie, Zhao; Wu, Xuehui; Xing, Junchao; Dong, Shiwu; Xu, Jianzhong

    2014-07-01

    The need for suitable bone grafts is high; however, there are limitations to all current graft sources, such as limited availability, the invasive harvest procedure, insufficient osteoinductive properties, poor biocompatibility, ethical problems, and degradation properties. The lack of osteoinductive properties is a common problem. As an allogenic bone graft, demineralized bone matrix (DBM) can overcome issues such as limited sources and comorbidities caused by invasive harvest; however, DBM is not sufficiently osteoinductive. Bone marrow has been known to magnify osteoinductive components for bone reconstruction because it contains osteogenic cells and factors. Mesenchymal stem cells (MSCs) derived from bone marrow are the gold standard for cell seeding in tissue-engineered biomaterials for bone repair, and these cells have demonstrated beneficial effects. However, the associated high cost and the complicated procedures limit the use of tissue-engineered bone constructs. To easily enrich more osteogenic cells and factors to DBM by selective cell retention technology, DBM is modified by a nanoscale self-assembling peptide (SAP) to form a composite DBM/SAP scaffold. By decreasing the pore size and increasing the charge interaction, DBM/SAP scaffolds possess a much higher enriching yield for osteogenic cells and factors compared with DBM alone scaffolds. At the same time, SAP can build a cellular microenvironment for cell adhesion, proliferation, and differentiation that promotes bone reconstruction. As a result, a suitable bone graft fabricated by DBM/SAP scaffolds and bone marrow represents a new strategy and product for bone transplantation in the clinic.

  14. Modulation of 3D Fibrin Matrix Stiffness by Intrinsic Fibrinogen–Thrombin Compositions and by Extrinsic Cellular Activity

    PubMed Central

    Duong, Haison; Wu, Benjamin

    2009-01-01

    Fibrin is a substance formed through catalytic conversion of coagulation constituents: fibrinogen and thrombin. The kinetics of the two constituents determines the structural properties of the fibrin architecture. We have shown previously that changing the fibrinogen and thrombin concentrations in the final three-dimensional (3D) fibrin matrix influenced cell proliferation and differentiation. In this study, we further examined the effect of changing fibrinogen and thrombin concentrations in the absence or presence of fibroblasts on the structural modulus or stiffness of 3D fibrin matrices. We have prepared fibroblast-free and fibroblast-embedded 3D fibrin matrices of different fibrinogen and thrombin formulations, and tested the stiffness of these constructs using standard mechanical testing assays. Results showed that there was a corresponding increase in stiffness with increasing thrombin and fibrinogen concentrations; the increase was more notable with fibrinogen and to a lesser degree with thrombin. The effect of fibroblasts on the stiffness of the fibrin construct was also examined. We have observed a small increase in the stiffness of the fibroblast-incorporated fibrin construct as they proliferated and exhibited spreading morphology. To our knowledge, this is the first comprehensive report detailing the relationship between fibrinogen and thrombin concentrations, cell proliferation, and stiffness in 3D fibrin matrices. The data obtained may lead to optimally design suitable bioscaffolds where we can control both cell proliferation and structural integrity for a variety of tissue engineering applications. PMID:19309239

  15. Road dust contribution to PM levels - Evaluation of the effectiveness of street washing activities by means of Positive Matrix Factorization

    NASA Astrophysics Data System (ADS)

    Karanasiou, Angeliki; Moreno, Teresa; Amato, Fulvio; Lumbreras, Julio; Narros, Adolfo; Borge, Rafael; Tobías, Aurelio; Boldo, Elena; Linares, Cristina; Pey, Jorge; Reche, Cristina; Alastuey, Andrés; Querol, Xavier

    2011-04-01

    The primary aim of this study was to quantify the contribution of road dust to airborne particulate matter (PM 10) and evaluate the effects of street washing on the mitigation of resuspension. With this purpose an intensive campaign was carried out in a heavily trafficked central road of Madrid (Spain) including PM 10 sampling and chemical analysis. PM 10 daily levels during dry, unwashed conditions were 2-15% higher than those present during the day after nightly street washing. However, this reduction is lower than the standard deviation of the PM 10 measurements. The diurnal variation of PM 10 revealed that a reduction in PM 10 was noticeable only during the morning hours. The emission sources for the urban area of Madrid were resolved by means of a receptor model, Positive Matrix Factorization, PMF. The results showed that the main sources were vehicle emissions, road dust, secondary aerosol including sulphate and nitrate, and soil. Vehicle emissions and road dust were the major contributor to PM 10 particle mass with similar average contributions of 31% and 29% respectively. The effect of street washing was also evaluated by examining the daily variation of the road dust source contribution between days with and without street washing. The mass contribution from the road dust source was ˜2 μg m -3 lower during the days that street washing was implemented with this corresponding to a reduction of 15% of its mass contribution during the days that the road surface was left untreated.

  16. Mesenchymal Transition of High-Grade Breast Carcinomas Depends on Extracellular Matrix Control of Myeloid Suppressor Cell Activity.

    PubMed

    Sangaletti, Sabina; Tripodo, Claudio; Santangelo, Alessandra; Castioni, Nadia; Portararo, Paola; Gulino, Alessandro; Botti, Laura; Parenza, Mariella; Cappetti, Barbara; Orlandi, Rosaria; Tagliabue, Elda; Chiodoni, Claudia; Colombo, Mario P

    2016-09-27

    The extracellular matrix (ECM) contributes to the biological and clinical heterogeneity of breast cancer, and different prognostic groups can be identified according to specific ECM signatures. In high-grade, but not low-grade, tumors, an ECM signature characterized by high SPARC expression (ECM3) identifies tumors with increased epithelial-to-mesenchymal transition (EMT), reduced treatment response, and poor prognosis. To better understand how this ECM3 signature is contributing to tumorigenesis, we expressed SPARC in isogenic cell lines and found that SPARC overexpression in tumor cells reduces their growth rate and induces EMT. SPARC expression also results in the formation of a highly immunosuppressive microenvironment, composed by infiltrating T regulatory cells, mast cells, and myeloid-derived suppressor cells (MDSCs). The ability of SPARC to induce EMT depended on the localization and suppressive function of myeloid cells, and inhibition of the suppressive function MDSCs by administration of aminobisphosphonates could revert EMT, rendering SPARC-overexpressing tumor cells sensitive to Doxil. We conclude that that SPARC is regulating the interplay between MDSCs and the ECM to drive the induction of EMT in tumor cells.

  17. Mesenchymal Transition of High-Grade Breast Carcinomas Depends on Extracellular Matrix Control of Myeloid Suppressor Cell Activity.

    PubMed

    Sangaletti, Sabina; Tripodo, Claudio; Santangelo, Alessandra; Castioni, Nadia; Portararo, Paola; Gulino, Alessandro; Botti, Laura; Parenza, Mariella; Cappetti, Barbara; Orlandi, Rosaria; Tagliabue, Elda; Chiodoni, Claudia; Colombo, Mario P

    2016-09-27

    The extracellular matrix (ECM) contributes to the biological and clinical heterogeneity of breast cancer, and different prognostic groups can be identified according to specific ECM signatures. In high-grade, but not low-grade, tumors, an ECM signature characterized by high SPARC expression (ECM3) identifies tumors with increased epithelial-to-mesenchymal transition (EMT), reduced treatment response, and poor prognosis. To better understand how this ECM3 signature is contributing to tumorigenesis, we expressed SPARC in isogenic cell lines and found that SPARC overexpression in tumor cells reduces their growth rate and induces EMT. SPARC expression also results in the formation of a highly immunosuppressive microenvironment, composed by infiltrating T regulatory cells, mast cells, and myeloid-derived suppressor cells (MDSCs). The ability of SPARC to induce EMT depended on the localization and suppressive function of myeloid cells, and inhibition of the suppressive function MDSCs by administration of aminobisphosphonates could revert EMT, rendering SPARC-overexpressing tumor cells sensitive to Doxil. We conclude that that SPARC is regulating the interplay between MDSCs and the ECM to drive the induction of EMT in tumor cells. PMID:27681434

  18. Calcium alginate gels as stem cell matrix-making paracrine stem cell activity available for enhanced healing after surgery.

    PubMed

    Schmitt, Andreas; Rödel, Philipp; Anamur, Cihad; Seeliger, Claudine; Imhoff, Andreas B; Herbst, Elmar; Vogt, Stephan; van Griensven, Martijn; Winter, Gerhard; Engert, Julia

    2015-01-01

    Regeneration after surgery can be improved by the administration of anabolic growth factors. However, to locally maintain these factors at the site of regeneration is problematic. The aim of this study was to develop a matrix system containing human mesenchymal stem cells (MSCs) which can be applied to the surgical site and allows the secretion of endogenous healing factors from the cells. Calcium alginate gels were prepared by a combination of internal and external gelation. The gelling behaviour, mechanical stability, surface adhesive properties and injectability of the gels were investigated. The permeability of the gels for growth factors was analysed using bovine serum albumin and lysozyme as model proteins. Human MSCs were isolated, cultivated and seeded into the alginate gels. Cell viability was determined by AlamarBlue assay and fluorescence microscopy. The release of human VEGF and bFGF from the cells was determined using an enzyme-linked immunoassay. Gels with sufficient mechanical properties were prepared which remained injectable through a syringe and solidified in a sufficient time frame after application. Surface adhesion was improved by the addition of polyethylene glycol 300,000 and hyaluronic acid. Humans MSCs remained viable for the duration of 6 weeks within the gels. Human VEGF and bFGF was found in quantifiable concentrations in cell culture supernatants of gels loaded with MSCs and incubated for a period of 6 weeks. This work shows that calcium alginate gels can function as immobilization matrices for human MSCs.

  19. STAT3 and ERK Signaling Pathways Are Implicated in the Invasion Activity by Oncostatin M through Induction of Matrix Metalloproteinases 2 and 9

    PubMed Central

    Ko, Hyun Sun; Park, Byung Joon; Choi, Sae Kyung; Kang, Hee Kyung; Kim, Ahyoung; Kim, Ho Shik; Park, In Yang

    2016-01-01

    Purpose Our previous studies have shown that oncostatin M (OSM) promotes trophoblast invasion activity through increased enzyme activity of matrix metalloproteinase (MMP)-2 and -9. We further investigated OSM-induced intracellular signaling mechanisms associated with these events in the immortalized human trophoblast cell line HTR8/SVneo. Materials and Methods We investigated the effects of OSM on RNA and protein expression of MMP-2 and -9 in the first-trimester extravillous trophoblast cell line (HTR8/SVneo) via Western blot. The selective signal transducer and activator of transcription (STAT)3 inhibitor, stattic, STAT3 siRNA, and extracellular signal-regulated kinase (ERK) siRNA were used to investigate STAT3 and ERK activation by OSM. The effects of STAT3 and ERK inhibitors on OSM-induced enzymatic activities of MMP-2 and -9 and invasion activity were further determined via Western blot and gelatin zymography. Results OSM-induced MMP-2 and -9 protein expression was significantly suppressed by STAT3 inhibition with stattic and STAT3 siRNA silencing, whereas the ERK1/2 inhibitor (U0126) and ERK silencing significantly suppressed OSM-induced MMP-2 protein expression. OSM-induced MMP-2 and MMP-9 enzymatic activities were significantly decreased by stattic pretreatment. The increased invasion activity induced by OSM was significantly suppressed by STAT3 and ERK1/2 inhibition, though to a greater extent by STAT3 inhibition. Conclusion Both STAT3 and ERK signaling pathways are involved in OSM-induced invasion activity of HTR8/SVneo cells. Activation of STAT3 appears to be critical for the OSM-mediated increase in invasiveness of HTR8/SVneo cells. PMID:26996579

  20. Activation of NF-kappaB by extracellular matrix is involved in spreading and glucose-stimulated insulin secretion of pancreatic beta cells.

    PubMed

    Hammar, Eva B; Irminger, Jean-Claude; Rickenbach, Katharina; Parnaud, Géraldine; Ribaux, Pascale; Bosco, Domenico; Rouiller, Dominique G; Halban, Philippe A

    2005-08-26

    Laminin-5-rich extracellular matrix derived from 804G cells (804G-ECM) engages beta1 integrins to induce spreading, improve glucose-stimulated insulin secretion (GSIS), and increase survival of pancreatic beta cells. The present study examines whether 804G-ECM activates the transcriptional activity of NF-kappaB and the involvement of NF-kappaB in those effects of 804G-ECM on pancreatic beta cells. 804G-ECM induces nuclear translocation and the DNA binding activity of the p65 subunit of NF-kappaB. 804G-ECM-induced nuclear translocation of NF-kappaB was weak as compared with that induced by interleukin-1beta. Transient 804G-ECM-induced DNA binding activity of NF-kappaB (peak at 2 h) and overexpression of NF-kappaB target genes IkappaB alpha and NF-kappaB1(p105) (peak at 4 h) were observed. When NF-kappaB was inhibited by an inhibitor of IkappaB alpha phosphorylation (Bay 11-7082) or by a recombinant adenovirus expressing the nonphosphorylatable form of IkappaB alpha, 804G-ECM-induced cell spreading and actin cytoskeleton organization were reduced. GSIS from cells on 804G-ECM was inhibited 5-fold, whereas cell survival was not affected. In summary, the results indicate that 804G-ECM induces a transient and moderate NF-kappaB activity. This study shows for the first time that ECM-induced NF-kappaB activity is necessary in maintaining GSIS, although it does not affect survival of pancreatic beta cells. The effects of ECM-induced NF-kappaB activity contrast with the deleterious effects of cytokine-induced NF-kappaB activity. It is proposed that transient and moderate NF-kappaB activity is essential for proper function of the pancreatic beta cell.

  1. Inhibition of matrix metalloproteinase-9 activity by doxycycline ameliorates RANK ligand-induced osteoclast differentiation in vitro and in vivo

    SciTech Connect

    Franco, Gilson C.N.; Nakanishi, Tadashi; Ohta, Kouji; Rosalen, Pedro L.; Groppo, Francisco C.; Bartlett, John D.; Stashenko, Philip; Taubman, Martin A.; Kawai, Toshihisa

    2011-06-10

    Tetracycline antibiotics, including doxycycli/e (DOX), have been used to treat bone resorptive diseases, partially because of their activity to suppress osteoclastogenesis induced by receptor activator of nuclear factor kappa B ligand (RANKL). However, their precise inhibitory mechanism remains unclear. Therefore, the present study examined the effect of Dox on osteoclastogenesis signaling induced by RANKL, both in vitro and in vivo. Although Dox inhibited RANKL-induced osteoclastogenesis and down-modulated the mRNA expression of functional osteoclast markers, including tartrate-resistant acid phosphatase (TRAP) and cathepsin K, Dox neither affected RANKL-induced MAPKs phosphorylation nor NFATc1 gene expression in RAW264.7 murine monocytic cells. Gelatin zymography and Western blot analyses showed that Dox down-regulated the enzyme activity of RANKL-induced MMP-9, but without affecting its protein expression. Furthermore, MMP-9 enzyme inhibitor also attenuated both RANKL-induced osteoclastogenesis and up-regulation of TRAP and cathepsin K mRNA expression, indicating that MMP-9 enzyme action is engaged in the promotion of RANKL-induced osteoclastogenesis. Finally, Dox treatment abrogated RANKL-induced osteoclastogenesis and TRAP activity in mouse calvaria along with the suppression of MMP9 enzyme activity, again without affecting the expression of MMP9 protein. These findings suggested that Dox inhibits RANKL-induced osteoclastogenesis by its inhibitory effect on MMP-9 enzyme activity independent of the MAPK-NFATc1 signaling cascade.

  2. The effect of acute and long-term physical activity on extracellular matrix and serglycin in human skeletal muscle

    PubMed Central

    Hjorth, Marit; Norheim, Frode; Meen, Astri J; Pourteymour, Shirin; Lee, Sindre; Holen, Torgeir; Jensen, Jørgen; Birkeland, Kåre I; Martinov, Vladimir N; Langleite, Torgrim M; Eckardt, Kristin; Drevon, Christian A; Kolset, Svein O

    2015-01-01

    Remodeling of extracellular matrix (ECM), including regulation of proteoglycans in skeletal muscle can be important for physiological adaptation to exercise. To investigate the effects of acute and long-term exercise on the expression of ECM-related genes and proteoglycans in particular, 26 middle-aged, sedentary men underwent a 12 weeks supervised endurance and strength training intervention and two acute, 45 min bicycle tests (70% VO2max), one at baseline and one after 12 weeks of training. Total gene expression in biopsies from m. vastus lateralis was measured with deep mRNA sequencing. After 45 min of bicycling approximately 550 gene transcripts were >50% upregulated. Of these, 28 genes (5%) were directly related to ECM. In response to long-term exercise of 12 weeks 289 genes exhibited enhanced expression (>50%) and 20% of them were ECM related. Further analyses of proteoglycan mRNA expression revealed that more than half of the proteoglycans expressed in muscle were significantly enhanced after 12 weeks intervention. The proteoglycan serglycin (SRGN) has not been studied in skeletal muscle and was one of few proteoglycans that showed increased expression after acute (2.2-fold, P < 0.001) as well as long-term exercise (1.4-fold, P < 0.001). Cultured, primary human skeletal muscle cells expressed and secreted SRGN. When the expression of SRGN was knocked down, the expression and secretion of serpin E1 (SERPINE1) increased. In conclusion, acute and especially long-term exercise promotes enhanced expression of several ECM components and proteoglycans. SRGN is a novel exercise-regulated proteoglycan in skeletal muscle with a potential role in exercise adaptation. PMID:26290530

  3. Matrix metalloproteinase-9 activity is associated with poor prognosis in T3-T4 node-negative colorectal cancer.

    PubMed

    Cho, Yong Beom; Lee, Woo Yong; Song, Sang Yong; Shin, Hee Jung; Yun, Seong Hyeon; Chun, Ho-Kyung

    2007-11-01

    Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is a novel membrane-anchored matrix metalloproteinase (MMP) inhibitor. RECK, MMP-2, and MMP-9 are believed to play crucial roles in tumor progression. This study was designed to examine the prognostic value of RECK, MMP-2, and MMP-9 in conjunction with other clinicopathologic factors in patients of T3-T4 node-negative colorectal cancer. RECK and MMP expression was observed using immunohistochemical analysis of the primary tumor from 89 patients with curatively resected T3-4 N0 colorectal cancer retrospectively. High RECK expression was observed in 51 cases, whereas expression was low in the other 38 cases. MMP-2 and MMP-9 expression was positive in cancer cells in 24 and 33 cases, respectively. RECK and MMP-2 expression was not significantly associated with any clinicopathologic factors. However, expression of MMP-9 was correlated with tumor location. A statistically significant inverse correlation was found between RECK and MMP-2 expression, and a statistically significant correlation was found between MMP-2 and MMP-9 expression. However, no association between RECK and MMP-9 expression was observed. Univariate analysis demonstrated that rectal tumor location, preoperative carcinoembryonic antigen more than 5 ng/mL, positive lymphatic invasion, less than 12 dissected lymph nodes, and positive MMP-9 expression were poor prognostic factors of disease-free survival. A multivariate analysis confirmed that enhanced MMP-9 expression was an independent and significant factor for prediction of a poor prognosis. In addition, positive lymphatic invasion and less than 12 dissected lymph nodes were significant negative prognostic factors. In conclusion, MMP-9 status represents a novel prognostic factor in evaluation of T3-T4 node-negative colorectal cancer.

  4. Performance of the readout electronics chain of the MICE Electron Muon Ranger

    NASA Astrophysics Data System (ADS)

    Lietti, D.; Berra, A.; Bolognini, D.; Hasan, S.; Mattera, A.; Prest, M.; Blondel, A.; Cadoux, F.; Graulich, J. S.; Masciocchi, F.; Wisting, H.; Giannini, G.; Iugovaz, D.; Reia, S.; Mascagna, V.; Vallazza, E.

    2010-04-01

    The MICE experiment intends to assess the feasibility of a Neutrino Factory and a Muon Collider and is based on the muon cooling technique: the muons pass through a series of absorbers decreasing their momentum while maintaining the beam size and reducing the emittance. At the end of the cooling section a detector able to distinguish single particles is required and is based on a KLOE-like front layer followed by fully active plastic scintillators, a calorimeter which in fact acts also as a tracker: the Electron Muon Ranger (EMR). The EMR detector consists of 50 planes organized in a x-y way, each one containing 59 scintillator bars with a triangular cross section. Each bar is readout by a single WLS fiber, inserted and glued in the bar hole, and connected to a 64 channel photomultiplier. On the other side of the bars, the fiber is connected to a single channel photomultiplier (one per plane) for the calibration and charge measurements. This paper presents the frontend and readout electronics of EMR which is based on VLSI ASICs and digital sampling to cope with the MICE rate. The analog info is provided by the single channel PMT whose signal is digitized by a VME waveform digitizer. The paper also describes the tests of the final electronics with the EMR prototype and of the first five long triangular bars at the CERN PS.

  5. Radiopurity assessment of the tracking readout for the NEXT double beta decay experiment

    NASA Astrophysics Data System (ADS)

    Cebrián, S.; Pérez, J.; Bandac, I.; Labarga, L.; Álvarez, V.; Barrado, A. I.; Bettini, A.; Borges, F. I. G. M.; Camargo, M.; Cárcel, S.; Cervera, A.; Conde, C. A. N.; Conde, E.; Dafni, T.; Díaz, J.; Esteve, R.; Fernandes, L. M. P.; Fernández, M.; Ferrario, P.; Ferreira, A. L.; Freitas, E. D. C.; Gehman, V. M.; Goldschmidt, A.; Gómez-Cadenas, J. J.; González-Díaz, D.; Gutiérrez, R. M.; Hauptman, J.; Hernando Morata, J. A.; Herrera, D. C.; Irastorza, I. G.; Laing, A.; Liubarsky, I.; López-March, N.; Lorca, D.; Losada, M.; Luzón, G.; Marí, A.; Martín-Albo, J.; Martínez, A.; Martínez-Lema, G.; Miller, T.; Monrabal, F.; Monserrate, M.; Monteiro, C. M. B.; Mora, F. J.; Moutinho, L. M.; Muñoz Vidal, J.; Nebot-Guinot, M.; Nygren, D.; Oliveira, C. A. B.; Ortiz de Solórzano, A.; Pérez Aparicio, J. L.; Querol, M.; Renner, J.; Ripoll, L.; Rodríguez, J.; Santos, F. P.; dos Santos, J. M. F.; Serra, L.; Shuman, D.; Simón, A.; Sofka, C.; Sorel, M.; Toledo, J. F.; Torrent, J.; Tsamalaidze, Z.; Veloso, J. F. C. A.; Villar, J. A.; Webb, R. C.; White, J. T.; Yahlali, N.

    2015-05-01

    The ``Neutrino Experiment with a Xenon Time-Projection Chamber'' (NEXT) is intended to investigate the neutrinoless double beta decay of 136Xe, which requires a severe suppression of potential backgrounds; therefore, an extensive screening and selection process is underway to control the radiopurity levels of the materials to be used in the experimental set-up of NEXT. The detector design combines the measurement of the topological signature of the event for background discrimination with the energy resolution optimization. Separate energy and tracking readout planes are based on different sensors: photomultiplier tubes for calorimetry and silicon multi-pixel photon counters for tracking. The design of a radiopure tracking plane, in direct contact with the gas detector medium, was specially challenging since the needed components like printed circuit boards, connectors, sensors or capacitors have typically, according to available information in databases and in the literature, activities too large for experiments requiring ultra-low background conditions. Here, the radiopurity assessment of tracking readout components based on gamma-ray spectroscopy using ultra-low background germanium detectors at the Laboratorio Subterr&aposaneo de Canfranc (Spain) is described. According to the obtained results, radiopure enough printed circuit boards made of kapton and copper, silicon photomultipliers and other required components, fulfilling the requirement of an overall background level in the region of interest of at most 8×10-4 counts keV-1 kg-1 y-1, have been identified.

  6. Fisetin regulates TPA-induced breast cell invasion by suppressing matrix metalloproteinase-9 activation via the PKC/ROS/MAPK pathways.

    PubMed

    Noh, Eun-Mi; Park, Yeon-Ju; Kim, Jeong-Mi; Kim, Mi-Seong; Kim, Ha-Rim; Song, Hyun-Kyung; Hong, On-Yu; So, Hong-Seob; Yang, Sei-Hoon; Kim, Jong-Suk; Park, Samg Hyun; Youn, Hyun-Jo; You, Yong-Ouk; Choi, Ki-Bang; Kwon, Kang-Beom; Lee, Young-Rae

    2015-10-01

    Invasion and metastasis are among the main causes of death in patients with malignant tumors. Fisetin (3,3',4',7-tetrahydroxyflavone), a natural flavonoid found in the smoke tree (Cotinus coggygria), is known to have antimetastatic effects on prostate and lung cancers; however, the effect of fisetin on breast cancer metastasis is unknown. The aim of this study was to determine the anti-invasive activity of fisetin in human breast cancer cells. Matrix metalloproteinase (MMP)-9 is a major component facilitating the invasion of many cancer tumor cell types, and thus the inhibitory effect of fisetin on MMP-9 expression in 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated human breast cancer cells was investigated in this study. Fisetin significantly attenuated TPA-induced cell invasion in MCF-7 human breast cancer cells, and was found to inhibit the activation of the PKCα/ROS/ERK1/2 and p38 MAPK signaling pathways. This effect was furthermore associated with reduced NF-κB activation, suggesting that the anti-invasive effect of fisetin on MCF-7 cells may result from inhibited TPA activation of NF-κB and reduced TPA activation of PKCα/ROS/ERK1/2 and p38 MAPK signals, ultimately leading to the downregulation of MMP-9 expression. Our findings indicate the role of fisetin in MCF-7 cell invasion, and clarify the underlying molecular mechanisms of this role, suggesting fisetin as a potential chemopreventive agent for breast cancer metastasis.

  7. Carbohydrate base co-polymers as an efficient immobilization matrix to enhance lipase activity for potential biocatalytic applications.

    PubMed

    Badgujar, Kirtikumar Chandulal; Bhanage, Bhalchandra Mahadeo

    2015-12-10

    In the present study, we have synthesized biocompatible hybrid blend of cellulosic polymers of hydroxypropyl-methyl-cellulose (HPMC) and chitosan (CHY) for the immobilization of Candida rugosa lipase (CRL). The immobilized biocatalyst HPMC:CHY:CRL was subjected for characterization such as SEM, TGA, water content analysis, lipase activity, specific activity and protein content analysis. The kinetic parameter study (Rmax/Km) demonstrated improved biocatalytic activity of lipase after immobilization on carbohydrate co-polymers of HPMC:CHY. This biocatalyst was then employed to study practical biocatalytic applications for kinetic resolution which provided 50% conversion and >94% enantiomeric excess of substrate/product (ees/eep). The protocol demonstrated excellent recyclability upto five cycles. Finally, we studied influence of immobilization on cellulosic polymers for substrate, structure and reactivity for kinetic resolution. Hence, we investigated R0 (initial reaction rate), E-value (enantioselectivity) and Ea (activation energy). This study confirms that, lipase immobilized on carbohydrate polymers had 3-4 folds higher biocatalytic activity as compared to crude CRL. PMID:26428176

  8. High Levels of 17β-Estradiol Are Associated with Increased Matrix Metalloproteinase-2 and Metalloproteinase-9 Activity in Tears of Postmenopausal Women with Dry Eye

    PubMed Central

    Shen, Guanglin; Ma, Xiaoping

    2016-01-01

    Purpose. To determine the serum levels of sex steroids and tear matrix metalloproteinases (MMP) 2 and 9 concentrations in postmenopausal women with dry eye. Methods. Forty-four postmenopausal women with dry eye and 22 asymptomatic controls were enrolled. Blood was drawn and analyzed for serum levels of sex steroids and lipids. Then, the following tests were performed: tear collection, Ocular Surface Disease Index (OSDI) questionnaire, fluorescein tear film break-up time (TBUT), corneal fluorescein staining, Schirmer test, and conjunctival impression cytology. The conjunctival mRNA expression and tear concentrations of MMP-2 and MMP-9 were measured. Results. Serum 17β-estradiol levels were significantly higher in the dry eye subjects than in the controls (P = 0.03), whereas there were no significant differences in levels of testosterone, dehydroepiandrosterone sulfate (DHEA-S), and progesterone. Tear MMP-2 and MMP-9 concentrations (P < 0.001), as well as the MMP-9 mRNA expression in conjunctival samples (P = 0.02), were significantly higher in dry eye subjects than in controls. Serum 17β-estradiol levels were positively correlated with tear MMP-2 and MMP-9 concentrations and negatively correlated with Schirmer test values. Conclusions. High levels of 17β-estradiol are associated with increased matrix metalloproteinase-2 and metalloproteinase-9 activity in tears of postmenopausal women with dry eye. PMID:26904272

  9. Controlled formation of reactive Fe particles dispersed in a carbon matrix active for the oxidation of aqueous contaminants with H₂O₂.

    PubMed

    Tristão, Juliana Cristina; de Mendonça, Fernanda Gomes; Lago, Rochel Montero; Ardisson, José Domingos

    2015-01-01

    In this work, reactive iron nanoparticles dispersed in a carbon matrix were produced by the controlled thermal decomposition of Fe(3+) ions in sucrose. During the sucrose decomposition, the Fe(3+) ions are reduced to form iron nanometric cores dispersed in a porous carbonaceous matrix. The materials were prepared with iron contents of 1, 4, and 8 wt.% and heated at 400, 600, and 800 °C. Analyses by X-ray diffraction, Mössbauer spectroscopy, magnetization measurements, Raman spectroscopy, termogravimetric analyses, BET surface area, scanning, and transmission electron microscopy showed that at 400 °C, the materials are composed essentially of Fe3O4 particles, while treatments at higher temperatures, i.e., 600 and 800 °C, produced phases such as Fe(0) and Fe3C. The composites were tested for the oxidation of methylene blue with H2O2 by a Fenton-type reaction and also H2O2 decomposition, showing better performance for the material containing 8 % of iron heated at 400 and 600 °C. These results are discussed in terms of Fe(2+) surface species in the Fe3O4 nanoparticles active for the Fenton reaction. PMID:24519746

  10. Development of a prototype PET scanner with depth-of-interaction measurement using solid-state photomultiplier arrays and parallel readout electronics.

    PubMed

    Shao, Yiping; Sun, Xishan; Lan, Kejian A; Bircher, Chad; Lou, Kai; Deng, Zhi

    2014-03-01

    In this study, we developed a prototype animal PET by applying several novel technologies to use solid-state photomultiplier (SSPM) arrays to measure the depth of interaction (DOI) and improve imaging performance. Each PET detector has an 8 × 8 array of about 1.9 × 1.9 × 30.0 mm(3) lutetium-yttrium-oxyorthosilicate scintillators, with each end optically connected to an SSPM array (16 channels in a 4 × 4 matrix) through a light guide to enable continuous DOI measurement. Each SSPM has an active area of about 3 × 3 mm(2), and its output is read by a custom-developed application-specific integrated circuit to directly convert analogue signals to digital timing pulses that encode the interaction information. These pulses are transferred to and are decoded by a field-programmable gate array-based time-to-digital convertor for coincident event selection and data acquisition. The independent readout of each SSPM and the parallel signal process can significantly improve the signal-to-noise ratio and enable the use of flexible algorithms for different data processes. The prototype PET consists of two rotating detector panels on a portable gantry with four detectors in each panel to provide 16 mm axial and variable transaxial field-of-view (FOV) sizes. List-mode ordered subset expectation maximization image reconstruction was implemented. The measured mean energy, coincidence timing and DOI resolution for a crystal were about 17.6%, 2.8 ns and 5.6 mm, respectively. The measured transaxial resolutions at the center of the FOV were 2.0 mm and 2.3 mm for images reconstructed with and without DOI, respectively. In addition, the resolutions across the FOV with DOI were substantially better than those without DOI. The quality of PET images of both a hot-rod phantom and mouse acquired with DOI was much higher than that of images obtained without DOI. This study demonstrates that SSPM arrays and advanced readout/processing electronics can be used to develop a practical DOI

  11. Quercetin Improves Postischemic Recovery of Heart Function in Doxorubicin-Treated Rats and Prevents Doxorubicin-Induced Matrix Metalloproteinase-2 Activation and Apoptosis Induction

    PubMed Central

    Barteková, Monika; Šimončíková, Petra; Fogarassyová, Mária; Ivanová, Monika; Okruhlicová, Ľudmila; Tribulová, Narcisa; Dovinová, Ima; Barančík, Miroslav

    2015-01-01

    Quercetin (QCT) is flavonoid that possesses various biological functions including anti-oxidative and radical-scavenging activities. Moreover, QCT exerts some preventive actions in treatment of cardiovascular diseases. The aim of present study was to explore effects of prolonged administration of QCT on changes induced by repeated application of doxorubicin (DOX) in rat hearts. We focused on the ultrastructure of myocardium, matrix metalloproteinases (MMPs), biometric parameters, and apoptosis induction. Our aim was also to examine effects of QCT on ischemic tolerance in hearts exposed to chronic effects of DOX, and to determine possible mechanisms underlying effects of QCT. Our results showed that QCT prevented several negative chronic effects of DOX: (I) reversed DOX-induced blood pressure increase; (II) mediated improvement of deleterious effects of DOX on ultrastructure of left ventricle; (III) prevented DOX-induced effects on tissue MMP-2 activation; and (iv) reversed effects of DOX on apoptosis induction and superoxide dismutase inhibition. Moreover, we showed that rat hearts exposed to effects of QCT were more resistant to ischemia/reperfusion injury. Effects of QCT on modulation of ischemic tolerance were linked to Akt kinase activation and connexin-43 up-regulation. Taken together, these results demonstrate that prolonged treatment with QCT prevented negative chronic effects of DOX on blood pressure, cellular damage, MMP-2 activation, and apoptosis induction. Moreover, QCT influenced myocardial responses to acute ischemic stress. These facts bring new insights into mechanisms of QCT action on rat hearts exposed to the chronic effects of DOX. PMID:25872140

  12. Jefferson Laboratory Hall A SuperBigBite spectrometer GEM readout scheme

    NASA Astrophysics Data System (ADS)

    Camsonne, Alexandre; Hall A SuperBigBite Collaboration

    2015-10-01

    The SuperBigBite spectrometer at Jefferson Laboratory in Hall A will rely on Gas Electron Multiplier trackers to achieve the required luminosity for large momentum transfer experiments. The readout electronics is based on the APV25 ASIC and the INFN VME board Multi Purpose Digitizer (MPD) Board. By using the optical readout of readout of the boards, all boards can be readout in parallel effectively increasing the data bandwidth for one crate by more than a factor of 10. With such scheme the readout of several samples become possible and background rejection can be applied to reduce the large quantity of data due to the high occupancy of detector before it is recorded. This special readout scheme based on the JLab electronics will be presented along with the online data reduction strategy for the GEM data.

  13. Infrared readout electronics; Proceedings of the Meeting, Orlando, FL, Apr. 21, 22, 1992

    NASA Technical Reports Server (NTRS)

    Fossum, Eric R. (Editor)

    1992-01-01

    The present volume on IR readout electronics discusses cryogenic readout using silicon devices, cryogenic readout using III-V and LTS devices, multiplexers for higher temperatures, and focal-plane signal processing electronics. Attention is given to the optimization of cryogenic CMOS processes for sub-10-K applications, cryogenic measurements of aerojet GaAs n-JFETs, inP-based heterostructure device technology for ultracold readout applications, and a three-terminal semiconductor-superconductor transimpedance amplifier. Topics addressed include unfulfilled needs in IR astronomy focal-plane readout electronics, IR readout integrated circuit technology for tactical missile systems, and radiation-hardened 10-bit A/D for FPA signal processing. Also discussed are the implementation of a noise reduction circuit for spaceflight IR spectrometers, a real-time processor for staring receivers, and a fiber-optic link design for INMOS transputers.

  14. Increased expression of matrix metalloproteinases (MMP)-2, MMP-9, and the urokinase-type plasminogen activator is associated with progression from benign to advanced ovarian cancer.

    PubMed

    Schmalfeldt, B; Prechtel, D; Härting, K; Späthe, K; Rutke, S; Konik, E; Fridman, R; Berger, U; Schmitt, M; Kuhn, W; Lengyel, E

    2001-08-01

    Proteases are linked to the malignant phenotype of different solid tumors. Therefore, the expression of the matrix metalloproteinase (MMP)-2 and MMP-9 and of the serine protease urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor type 1 (PAI-1) in the progression of ovarian cancer was investigated. Gelatinolytic activity and protein expression of MMP-2 and MMP-9 were analyzed in tissue extracts of 19 cystadenomas and 18 low malignant potential (LMP) tumors, as well as 41 primary tumors of advanced ovarian cancer stage International Federation of Gynecology and Obstetrics IIIc/IV and their corresponding omentum metastases by quantitative gelatin zymography and Western blot. In the same tissue extracts, antigen levels of uPA and its inhibitor PAI-1 were determined by ELISA. Protein expression of pro-MMP-2 (72 kDa) and pro-MMP-9 (92 kDa as well as antigen levels of uPA and PAI-1 were low in benign ovarian tumors but increased significantly from LMP tumors to advanced ovarian cancers. The highest values of all of the proteolytic factors were detected in omentum metastases. Active MMP-2 enzyme (62 kDa) was detected only in ovarian cancer (66%) and corresponding metastases (93%) but never in benign or LMP tumors. The activation rate of MMP-2 to its active isoform was higher in the metastases. Comparing both proteolytic systems, higher PAI-1 concentrations were consistently found in cancers with high pro-MMP-9 expression. These data indicate that members of the plasminogen activator system, as well as the metalloproteinases MMP-2/9, increase with growing malignant potential of ovarian tumors. These findings are of particular relevance to the development of protease inhibitors as new therapeutic approaches in ovarian cancer.

  15. Priming Endothelial Cells With a Melanoma-Derived Extracellular Matrix Triggers the Activation of αvβ3/VEGFR2 Axis.

    PubMed

    Helal-Neto, Edward; Brandão-Costa, Renata M; Saldanha-Gama, Roberta; Ribeiro-Pereira, Cristiane; Midlej, Victor; Benchimol, Marlene; Morandi, Verônica; Barja-Fidalgo, Christina

    2016-11-01

    The unique composition of tumor-produced extracellular matrix (ECM) can be a determining factor in changing the profile of endothelial cells in the tumor microenvironment. As the main receptor for ECM proteins, integrins can activate a series of signaling pathways related to cell adhesion, migration, and differentiation of endothelial cells that interact with ECM proteins. We studied the direct impact of the decellularized ECM produced by a highly metastatic human melanoma cell line (MV3) on the activation of endothelial cells and identified the intracellular signaling pathways associated with cell differentiation. Our data show that compared to the ECM derived from a human melanocyte cell line (NGM-ECM), ECM produced by a melanoma cell line (MV3-ECM) is considerably different in ultrastructural organization and composition and possesses a higher content of tenascin-C and laminin and a lower expression of fibronectin. When cultured directly on MV3-ECM, endothelial cells change morphology and show increased adhesion, migration, proliferation, and tubulogenesis. Interaction of endothelial cells with MV3-ECM induces the activation of integrin signaling, increasing FAK phosphorylation and its association with Src, which activates VEGFR2, potentiating the receptor response to VEGF. The blockage of αvβ3 integrin inhibited the FAK-Src association and VEGFR activation, thus reducing tubulogenesis. Together, our data suggest that the interaction of endothelial cells with the melanoma-ECM triggers integrin-dependent signaling, leading to Src pathway activation that may potentiate VEGFR2 activation and up-regulate angiogenesis. J. Cell. Physiol. 231: 2464-2473, 2016. © 2016 Wiley Periodicals, Inc.

  16. Effects of eplerenone on the activation of matrix metalloproteinase-2 stimulated by high glucose and interleukin-1β in human cardiac fibroblasts.

    PubMed

    Chi, J F; Uzui, H; Guo, H Y; Ueda, T; Lee, J D

    2014-01-01

    The aim of this study was to determine the influence of high glucose (HG) and interleukin (IL)-1β on human cardiac fibroblast (HCF) functions, and to evaluate the effects of eplerenone in these responses. HCFs were cultured in normal or HG media in the absence or presence of IL-1β and/or eplerenone. We assessed matrix metalloproteinase-2 (MMP-2) activity in the supernatant by in-gel zymography, and determined mRNA expression levels of MMP-2 and tissue inhibitor of metalloproteinase-2 (TIMP-2) by reverse transcription-polymerase chain reaction. Equimolar D-mannitol was used as an osmotic control. HG stimulated MMP-2 activity and promoted MMP-2 mRNA synthesis. Increased effects were also observed in equimolar D-mannitol treatments, but these effects were weaker compared to those of glucose. The combination of HG and IL-1β resulted in a 2-fold increase in MMP-2 activity and mRNA expression compared with HG or IL-1β alone. Increases in HG- or IL-1β-induced MMP-2 activity and mRNA expression were blocked by eplerenone. Neither HG nor IL-1β affected TIMP-2 mRNA expression. HG increased MMP-2 activity by regulation of MMP- 2 mRNA expression in HCFs through osmotic and non-osmotic pathways. Synergistic effects of IL-1β added to HG media on MMP-2 activity and mRNA expression were observed in HCFs. Eplerenone normalized the effect of MMP-2 activity and HG- or IL-1β-induced expression in HCFs.

  17. Priming Endothelial Cells With a Melanoma-Derived Extracellular Matrix Triggers the Activation of αvβ3/VEGFR2 Axis.

    PubMed

    Helal-Neto, Edward; Brandão-Costa, Renata M; Saldanha-Gama, Roberta; Ribeiro-Pereira, Cristiane; Midlej, Victor; Benchimol, Marlene; Morandi, Verônica; Barja-Fidalgo, Christina

    2016-11-01

    The unique composition of tumor-produced extracellular matrix (ECM) can be a determining factor in changing the profile of endothelial cells in the tumor microenvironment. As the main receptor for ECM proteins, integrins can activate a series of signaling pathways related to cell adhesion, migration, and differentiation of endothelial cells that interact with ECM proteins. We studied the direct impact of the decellularized ECM produced by a highly metastatic human melanoma cell line (MV3) on the activation of endothelial cells and identified the intracellular signaling pathways associated with cell differentiation. Our data show that compared to the ECM derived from a human m