Science.gov

Sample records for active pixel matrix

  1. 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.

  2. Monolithic active pixel matrix with binary counters (MAMBO III) ASIC

    SciTech Connect

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

    2010-01-01

    Monolithic Active Matrix with Binary Counters (MAMBO) is a counting ASIC designed for detecting and measuring low energy X-rays from 6-12keV. 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.

  3. 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}.

  4. X-RAY ACTIVE MATRIX PIXEL SENSORS BASEDON J-FET TECHNOLOGY DEVELOPED FOR THE LINAC COHERENT LIGHT SOURCE.

    SciTech Connect

    CARINI,G.A.; CHEN, W.; LI, Z.; REHAK, P.; SIDDONS, D.P.

    2007-10-29

    An X-ray Active Matrix Pixel Sensor (XAMPS) is being developed for recording data for the X-ray Pump Probe experiment at the Linac Coherent Light Source (LCLS). Special attention has to be paid to some technological challenges that this design presents. New processes were developed and refined to address problems encountered during previous productions of XAMPS. The development of these critical steps and corresponding tests results are reported here.

  5. 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

  6. An investigation of signal performance enhancements achieved through innovative pixel design across several generations of indirect detection, active matrix, flat-panel arrays

    PubMed Central

    Antonuk, Larry E.; Zhao, Qihua; El-Mohri, Youcef; Du, Hong; Wang, Yi; Street, Robert A.; Ho, Jackson; Weisfield, Richard; Yao, William

    2009-01-01

    Active matrix flat-panel imager (AMFPI) technology is being employed for an increasing variety of imaging applications. An important element in the adoption of this technology has been significant ongoing improvements in optical signal collection achieved through innovations in indirect detection array pixel design. Such improvements have a particularly beneficial effect on performance in applications involving low exposures and∕or high spatial frequencies, where detective quantum efficiency is strongly reduced due to the relatively high level of additive electronic noise compared to signal levels of AMFPI devices. In this article, an examination of various signal properties, as determined through measurements and calculations related to novel array designs, is reported in the context of the evolution of AMFPI pixel design. For these studies, dark, optical, and radiation signal measurements were performed on prototype imagers incorporating a variety of increasingly sophisticated array designs, with pixel pitches ranging from 75 to 127 μm. For each design, detailed measurements of fundamental pixel-level properties conducted under radiographic and fluoroscopic operating conditions are reported and the results are compared. A series of 127 μm pitch arrays employing discrete photodiodes culminated in a novel design providing an optical fill factor of ∼80% (thereby assuring improved x-ray sensitivity), and demonstrating low dark current, very low charge trapping and charge release, and a large range of linear signal response. In two of the designs having 75 and 90 μm pitches, a novel continuous photodiode structure was found to provide fill factors that approach the theoretical maximum of 100%. Both sets of novel designs achieved large fill factors by employing architectures in which some, or all of the photodiode structure was elevated above the plane of the pixel addressing transistor. Generally, enhancement of the fill factor in either discrete or continuous

  7. Source Driver Channel Reduction Schemes Employing Corresponding Pixel Alignments for Current Programming Active-Matrix Organic Light-Emitting Diode Displays

    NASA Astrophysics Data System (ADS)

    Hong, Soon-Kwang; Oh, Du-Hwan; Jeong, Seok-Hee; Park, Young-Ju; Kim, Byeong-Koo; Ha, Yong-Min; Jang, Jin

    2008-03-01

    We propose two types of novel scheme for reducing the number of output channels of driver-integrated circuit (D-IC) for the current programming compensation pixel structures of active-matrix organic light-emitting diodes (AMOLEDs). One is a 2:1 data demultiplexing technique that can reduce the number of output channels of D-IC by half. The proposed second scheme is a vertically aligned red (R), green (G), and blue (B) subpixel scheme instead of a horizontally aligned R-G-B subpixel one, which is regarded as the conventional pixel alignment scheme. We have also successfully implemented these schemes in a 2.4-in.-sized QCIF + (176 × RGB × 220) AMOLED using p-type excimer laser annealing (ELA) low-temperature polycrystalline silicon (LTPS) technology and evaluated key performance characteristics.

  8. Imaging by photon counting with 256x256 pixel matrix

    NASA Astrophysics Data System (ADS)

    Tlustos, Lukas; Campbell, Michael; Heijne, Erik H. M.; Llopart, Xavier

    2004-09-01

    Using 0.25µm standard CMOS we have developed 2-D semiconductor matrix detectors with sophisticated functionality integrated inside each pixel of a hybrid sensor module. One of these sensor modules is a matrix of 256x256 square 55µm pixels intended for X-ray imaging. This device is called 'Medipix2' and features a fast amplifier and two-level discrimination for signals between 1000 and 100000 equivalent electrons, with overall signal noise ~150 e- rms. Signal polarity and comparator thresholds are programmable. A maximum count rate of nearly 1 MHz per pixel can be achieved, which corresponds to an average flux of 3x10exp10 photons per cm2. The selected signals can be accumulated in each pixel in a 13-bit register. The serial readout takes 5-10 ms. A parallel readout of ~300 µs could also be used. Housekeeping functions such as local dark current compensation, test pulse generation, silencing of noisy pixels and threshold tuning in each pixel contribute to the homogeneous response over a large sensor area. The sensor material can be adapted to the energy of the X-rays. Best results have been obtained with high-resistivity silicon detectors, but also CdTe and GaAs detectors have been used. The lowest detectable X-ray energy was about 4 keV. Background measurements have been made, as well as measurements of the uniformity of imaging by photon counting. Very low photon count rates are feasible and noise-free at room temperature. The readout matrix can be used also with visible photons if an energy or charge intensifier structure is interposed such as a gaseous amplification layer or a microchannel plate or acceleration field in vacuum.

  9. High accuracy injection circuit for the calibration of a large pixel sensor matrix

    NASA Astrophysics Data System (ADS)

    Quartieri, E.; Comotti, D.; Manghisoni, M.

    2013-08-01

    Semiconductor pixel detectors, for particle tracking and vertexing in high energy physics experiments as well as for X-ray imaging, in particular for synchrotron light sources and XFELs, require a large area sensor matrix. This work will discuss the design and the characterization of a high-linearity, low dispersion injection circuit to be used for pixel-level calibration of detector readout electronics in a large pixel sensor matrix. The circuit provides a useful tool for the characterization of the readout electronics of the pixel cell unit for both monolithic active pixel sensors and hybrid pixel detectors. In the latter case, the circuit allows for precise analogue test of the readout channel already at the chip level, when no sensor is connected. Moreover, it provides a simple means for calibration of readout electronics once the detector has been connected to the chip. Two injection techniques can be provided by the circuit: one for a charge sensitive amplification and the other for a transresistance readout channel. The aim of the paper is to describe the architecture and the design guidelines of the calibration circuit, which has been implemented in a 130 nm CMOS technology. Moreover, experimental results of the proposed injection circuit will be presented in terms of linearity and dispersion.

  10. Active Pixel Sensors: Are CCD's Dinosaurs?

    NASA Technical Reports Server (NTRS)

    Fossum, Eric R.

    1993-01-01

    Charge-coupled devices (CCD's) are presently the technology of choice for most imaging applications. In the 23 years since their invention in 1970, they have evolved to a sophisticated level of performance. However, as with all technologies, we can be certain that they will be supplanted someday. In this paper, the Active Pixel Sensor (APS) technology is explored as a possible successor to the CCD. An active pixel is defined as a detector array technology that has at least one active transistor within the pixel unit cell. The APS eliminates the need for nearly perfect charge transfer -- the Achilles' heel of CCDs. This perfect charge transfer makes CCD's radiation 'soft,' difficult to use under low light conditions, difficult to manufacture in large array sizes, difficult to integrate with on-chip electronics, difficult to use at low temperatures, difficult to use at high frame rates, and difficult to manufacture in non-silicon materials that extend wavelength response.

  11. Active pixel sensor with intra-pixel charge transfer

    NASA Technical Reports Server (NTRS)

    Fossum, Eric R. (Inventor); Mendis, Sunetra (Inventor); Kemeny, Sabrina E. (Inventor)

    1995-01-01

    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, a readout circuit including at least an output field effect transistor formed in the substrate, and a charge coupled device section formed on the substrate adjacent the photogate having a sensing node connected to the output transistor and at least one charge coupled device stage for transferring charge from the underlying portion of the substrate to the sensing node.

  12. Active pixel sensor with intra-pixel charge transfer

    NASA Technical Reports Server (NTRS)

    Fossum, Eric R. (Inventor); Mendis, Sunetra (Inventor); Kemeny, Sabrina E. (Inventor)

    2003-01-01

    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, a readout circuit including at least an output field effect transistor formed in the substrate, and a charge coupled device section formed on the substrate adjacent the photogate having a sensing node connected to the output transistor and at least one charge coupled device stage for transferring charge from the underlying portion of the substrate to the sensing node.

  13. Active pixel sensor with intra-pixel charge transfer

    NASA Technical Reports Server (NTRS)

    Fossum, Eric R. (Inventor); Mendis, Sunetra (Inventor); Kemeny, Sabrina E. (Inventor)

    2004-01-01

    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, a readout circuit including at least an output field effect transistor formed in the substrate, and a charge coupled device section formed on the substrate adjacent the photogate having a sensing node connected to the output transistor and at least one charge coupled device stage for transferring charge from the underlying portion of the substrate to the sensing node.

  14. Active pixel sensor array with electronic shuttering

    NASA Technical Reports Server (NTRS)

    Fossum, Eric R. (Inventor)

    2002-01-01

    An active pixel cell includes electronic shuttering capability. The cell can be shuttered to prevent additional charge accumulation. One mode transfers the current charge to a storage node that is blocked against accumulation of optical radiation. The charge is sampled from a floating node. Since the charge is stored, the node can be sampled at the beginning and the end of every cycle. Another aspect allows charge to spill out of the well whenever the charge amount gets higher than some amount, thereby providing anti blooming.

  15. CMOS Active Pixel Sensor Technology and Reliability Characterization Methodology

    NASA Technical Reports Server (NTRS)

    Chen, Yuan; Guertin, Steven M.; Pain, Bedabrata; Kayaii, Sammy

    2006-01-01

    This paper describes the technology, design features and reliability characterization methodology of a CMOS Active Pixel Sensor. Both overall chip reliability and pixel reliability are projected for the imagers.

  16. Radiation tolerance of CMOS monolithic active pixel sensors with self-biased pixels

    NASA Astrophysics Data System (ADS)

    Deveaux, M.; Amar-Youcef, S.; Besson, A.; Claus, G.; Colledani, C.; Dorokhov, M.; Dritsa, C.; Dulinski, W.; Fröhlich, I.; Goffe, M.; Grandjean, D.; Heini, S.; Himmi, A.; Hu, C.; Jaaskelainen, K.; Müntz, C.; Shabetai, A.; Stroth, J.; Szelezniak, M.; Valin, I.; Winter, M.

    2010-12-01

    CMOS monolithic active pixel sensors (MAPS) are proposed as a technology for various vertex detectors in nuclear and particle physics. We discuss the mechanisms of ionizing radiation damage on MAPS hosting the dead time free, so-called self bias pixel. Moreover, we introduce radiation hardened sensor designs which allow operating detectors after exposing them to irradiation doses above 1 Mrad.

  17. Matrix:. AN Innovative Pixel Ionization Chamber for On-Line Beam Monitoring in Hadrontherapy

    NASA Astrophysics Data System (ADS)

    Braccini, S.; Pitta', G.; Donetti, M.; Cirio, R.; La Rosa, A.; Garella, M. A.; Giordanengo, S.; Marchetto, F.; Peroni, C.

    2006-04-01

    The control of intensity, position and shape of clinical beams are key issues in the treatment of tumours using hadron beams, especially in the case of active dose distribution systems. For this purpose an innovative pixel ionization chamber, named MATRIX, has been designed, constructed and tested. The chamber is conceived to be located very near the patient to precisely monitor the beam parameters used to verify the treatment planning specifications. MATRIX operates in air and is characterized by a 21 × 21 cm2 sensitive area subdivided in 1024 pixels of 6.5 × 6.5 mm2. To minimize the amount of material crossed by the beam, the anode is made of a 50 μm kapton foil, with a deposit of 17 μm copper on each side. A very sensitive electronics is used for the readout, based on a dedicated chip. In this paper the construction of the chamber and the very positive results of the first beam tests are described.

  18. CMOS Active-Pixel Image Sensor With Simple Floating Gates

    NASA Technical Reports Server (NTRS)

    Fossum, Eric R.; Nakamura, Junichi; Kemeny, Sabrina E.

    1996-01-01

    Experimental complementary metal-oxide/semiconductor (CMOS) active-pixel image sensor integrated circuit features simple floating-gate structure, with metal-oxide/semiconductor field-effect transistor (MOSFET) as active circuit element in each pixel. Provides flexibility of readout modes, no kTC noise, and relatively simple structure suitable for high-density arrays. Features desirable for "smart sensor" applications.

  19. Active pixel imagers incorporating pixel-level amplifiers based on polycrystalline-silicon thin-film transistors.

    PubMed

    El-Mohri, Youcef; Antonuk, Larry E; Koniczek, Martin; Zhao, Qihua; Li, Yixin; Street, Robert A; Lu, Jeng-Ping

    2009-07-01

    Active matrix, flat-panel imagers (AMFPIs) employing a 2D matrix of a-Si addressing TFTs have become ubiquitous in many x-ray imaging applications due to their numerous advantages. However, under conditions of low exposures and/or high spatial resolution, their signal-to-noise performance is constrained by the modest system gain relative to the electronic additive noise. In this article, a strategy for overcoming this limitation through the incorporation of in-pixel amplification circuits, referred to as active pixel (AP) architectures, using polycrystalline-silicon (poly-Si) TFTs is reported. Compared to a-Si, poly-Si offers substantially higher mobilities, enabling higher TFT currents and the possibility of sophisticated AP designs based on both n- and p-channel TFTs. Three prototype indirect detection arrays employing poly-Si TFTs and a continuous a-Si photodiode structure were characterized. The prototypes consist of an array (PSI-1) that employs a pixel architecture with a single TFT, as well as two arrays (PSI-2 and PSI-3) that employ AP architectures based on three and five TFTs, respectively. While PSI-1 serves as a reference with a design similar to that of conventional AMFPI arrays, PSI-2 and PSI-3 incorporate additional in-pixel amplification circuitry. Compared to PSI-1, results of x-ray sensitivity demonstrate signal gains of approximately 10.7 and 20.9 for PSI-2 and PSI-3, respectively. These values are in reasonable agreement with design expectations, demonstrating that poly-Si AP circuits can be tailored to provide a desired level of signal gain. PSI-2 exhibits the same high levels of charge trapping as those observed for PSI-1 and other conventional arrays employing a continuous photodiode structure. For PSI-3, charge trapping was found to be significantly lower and largely independent of the bias voltage applied across the photodiode. MTF results indicate that the use of a continuous photodiode structure in PSI-1, PSI-2, and PSI-3 results in

  20. Active pixel imagers incorporating pixel-level amplifiers based on polycrystalline-silicon thin-film transistors

    PubMed Central

    El-Mohri, Youcef; Antonuk, Larry E.; Koniczek, Martin; Zhao, Qihua; Li, Yixin; Street, Robert A.; Lu, Jeng-Ping

    2009-01-01

    Active matrix, flat-panel imagers (AMFPIs) employing a 2D matrix of a-Si addressing TFTs have become ubiquitous in many x-ray imaging applications due to their numerous advantages. However, under conditions of low exposures and∕or high spatial resolution, their signal-to-noise performance is constrained by the modest system gain relative to the electronic additive noise. In this article, a strategy for overcoming this limitation through the incorporation of in-pixel amplification circuits, referred to as active pixel (AP) architectures, using polycrystalline-silicon (poly-Si) TFTs is reported. Compared to a-Si, poly-Si offers substantially higher mobilities, enabling higher TFT currents and the possibility of sophisticated AP designs based on both n- and p-channel TFTs. Three prototype indirect detection arrays employing poly-Si TFTs and a continuous a-Si photodiode structure were characterized. The prototypes consist of an array (PSI-1) that employs a pixel architecture with a single TFT, as well as two arrays (PSI-2 and PSI-3) that employ AP architectures based on three and five TFTs, respectively. While PSI-1 serves as a reference with a design similar to that of conventional AMFPI arrays, PSI-2 and PSI-3 incorporate additional in-pixel amplification circuitry. Compared to PSI-1, results of x-ray sensitivity demonstrate signal gains of ∼10.7 and 20.9 for PSI-2 and PSI-3, respectively. These values are in reasonable agreement with design expectations, demonstrating that poly-Si AP circuits can be tailored to provide a desired level of signal gain. PSI-2 exhibits the same high levels of charge trapping as those observed for PSI-1 and other conventional arrays employing a continuous photodiode structure. For PSI-3, charge trapping was found to be significantly lower and largely independent of the bias voltage applied across the photodiode. MTF results indicate that the use of a continuous photodiode structure in PSI-1, PSI-2, and PSI-3 results in optical fill

  1. Using an Active Pixel Sensor In A Vertex Detector

    SciTech Connect

    Matis, Howard S.; Bieser, Fred; Chen, Yandong; Gareus, Robin; Kleinfelder, Stuart; Oldenburg, Markus; Retiere, Fabrice; Ritter, HansGeorg; Wieman, Howard H.; Wurzel, Samuel E.; Yamamoto, Eugene

    2004-04-22

    Research has shown that Active Pixel CMOS sensors can detect charged particles. We have been studying whether this process can be used in a collider environment. In particular, we studied the effect of radiation with 55 MeV protons. These results show that a fluence of about 2 x 10{sup 12} protons/cm{sup 2} reduces the signal by a factor of two while the noise increases by 25%. A measurement 6 months after exposure shows that the silicon lattice naturally repairs itself. Heating the silicon to 100 C reduced the shot noise and increased the collected charge. CMOS sensors have a reduced signal to noise ratio per pixel because charge diffuses to neighboring pixels. We have constructed a photogate to see if this structure can collect more charge per pixel. Results show that a photogate does collect charge in fewer pixels, but it takes about 15 ms to collect all of the electrons produced by a pulse of light.

  2. 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.

  3. Pixel response function experimental techniques and analysis of active pixel sensor star cameras

    NASA Astrophysics Data System (ADS)

    Fumo, Patrick; Waldron, Erik; Laine, Juha-Pekka; Evans, Gary

    2015-04-01

    The pixel response function (PRF) of a pixel within a focal plane is defined as the pixel intensity with respect to the position of a point source within the pixel. One of its main applications is in the field of astrometry, which is a branch of astronomy that deals with positioning data of a celestial body for tracking movement or adjusting the attitude of a spacecraft. Complementary metal oxide semiconductor (CMOS) image sensors generally offer better radiation tolerance to protons and heavy ions than CCDs making them ideal candidates for space applications aboard satellites, but like all image sensors they are limited by their spatial frequency response, better known as the modulation transfer function. Having a well-calibrated PRF allows us to eliminate some of the uncertainty in the spatial response of the system providing better resolution and a more accurate centroid estimation. This paper describes the experimental setup for determining the PRF of a CMOS image sensor and analyzes the effect on the oversampled point spread function (PSF) of an image intensifier, as well as the effects due to the wavelength of light used as a point source. It was found that using electron bombarded active pixel sensor (EBAPS) intensification technology had a significant impact on the PRF of the camera being tested as a result of an increase in the amount of carrier diffusion between collection sites generated by the intensification process. Taking the full width at half maximum (FWHM) of the resulting data, it was found that the intensified version of a CMOS camera exhibited a PSF roughly 16.42% larger than its nonintensified counterpart.

  4. Fault tolerant photodiode and photogate active pixel sensors

    NASA Astrophysics Data System (ADS)

    Jung, Cory; Chapman, Glenn H.; La Haye, Michelle L.; Djaja, Sunjaya; Cheung, Desmond Y. H.; Lin, Henry; Loo, Edward; Audet, Yves R.

    2005-03-01

    As the pixel counts of digital imagers increase, the challenge of maintaining high yields and ensuring reliability over an imager"s lifetime increases. A fault tolerant active pixel sensor (APS) has been designed to meet this need by splitting an APS in half and operating both halves in parallel. The fault tolerant APS will perform normally in the no defect case and will produce approximately half the output for single defects. Thus, the entire signal can be recovered by multiplying the output by two. Since pixels containing multiple defects are rare, this design can correct for most defects allowing for higher production yields. Fault tolerant photodiode and photogate APS" were fabricated in 0.18-micron technology. Testing showed that the photodiode APS could correct for optically induced and electrically induced faults, within experimental error. The photogate APS was only tested for optically induced defects and also corrects for defects within experimental error. Further testing showed that the sensitivity of fault tolerant pixels was approximately 2-3 times more sensitive than the normal pixels. HSpice simulations of the fault tolerant APS circuit did not show increased sensitivity, however an equivalent normal APS circuit with twice width readout and row transistors was 1.90 times more sensitive than a normal pixel.

  5. ALPIDE, the Monolithic Active Pixel Sensor for the ALICE ITS upgrade

    NASA Astrophysics Data System (ADS)

    Mager, M.

    2016-07-01

    A new 10 m2 inner tracking system based on seven concentric layers of Monolithic Active Pixel Sensors will be installed in the ALICE experiment during the second long shutdown of LHC in 2019-2020. The monolithic pixel sensors will be fabricated in the 180 nm CMOS Imaging Sensor process of TowerJazz. The ALPIDE design takes full advantage of a particular process feature, the deep p-well, which allows for full CMOS circuitry within the pixel matrix, while at the same time retaining the full charge collection efficiency. Together with the small feature size and the availability of six metal layers, this allowed a continuously active low-power front-end to be placed into each pixel and an in-matrix sparsification circuit to be used that sends only the addresses of hit pixels to the periphery. This approach led to a power consumption of less than 40 mWcm-2, a spatial resolution of around 5 μm, a peaking time of around 2 μs, while being radiation hard to some 1013 1 MeVneq /cm2, fulfilling or exceeding the ALICE requirements. Over the last years of R & D, several prototype circuits have been used to verify radiation hardness, and to optimize pixel geometry and in-pixel front-end circuitry. The positive results led to a submission of full-scale (3 cm×1.5 cm) sensor prototypes in 2014. They are being characterized in a comprehensive campaign that also involves several irradiation and beam tests. A summary of the results obtained and prospects towards the final sensor to instrument the ALICE Inner Tracking System are given.

  6. Matrix light and pixel light: optical system architecture and requirements to the light source

    NASA Astrophysics Data System (ADS)

    Spinger, Benno; Timinger, Andreas L.

    2015-09-01

    Modern Automotive headlamps enable improved functionality for more driving comfort and safety. Matrix or Pixel light headlamps are not restricted to either pure low beam functionality or pure high beam. Light in direction of oncoming traffic is selectively switched of, potential hazard can be marked via an isolated beam and the illumination on the road can even follow a bend. The optical architectures that enable these advanced functionalities are diverse. Electromechanical shutters and lens units moved by electric motors were the first ways to realize these systems. Switching multiple LED light sources is a more elegant and mechanically robust solution. While many basic functionalities can already be realized with a limited number of LEDs, an increasing number of pixels will lead to more driving comfort and better visibility. The required optical system needs not only to generate a desired beam distribution with a high angular dynamic, but also needs to guarantee minimal stray light and cross talk between the different pixels. The direct projection of the LED array via a lens is a simple but not very efficient optical system. We discuss different optical elements for pre-collimating the light with minimal cross talk and improved contrast between neighboring pixels. Depending on the selected optical system, we derive the basic light source requirements: luminance, surface area, contrast, flux and color homogeneity.

  7. Direct integration of a 4-pixel emissive display into a knit fabric matrix

    NASA Astrophysics Data System (ADS)

    Coyle, Jared P.; Li, Bin; Dion, Genevieve; Fontecchio, Adam K.

    2013-03-01

    There exists a growing demand for displays in wearable applications. Wearable displays have traditionally been state-ofthe- art flexible designs that are subsequently mounted onto clothing fabric. Ideally, such a design would itself be fabricintegrated. Recently, much attention has been placed on work involving the weaving of photonic bandgap and other optical fibers to create a true fabric based display. Little exists in the technical literature concerning knit-based fabric displays. In this research, a prototype 4-pixel emissive fabric display is demonstrated. Conductive silver-plated nylon fibers act as a cathode. The fibers are coated in poly-2-methoxy-5-(2'-ethylhexyloxy)-p-phenylene vinylene (MEHPPV). When this layered structure is placed in contact with a separate metallic fiber (functions as an anode), a singlelayer PLED is formed. After drying and annealing, coated fibers are knit into a fabric matrix using a Shima Seiki SSG202SV automated knitting machine. The knit pattern itself provides a passive matrix addressing system similar to that of a more simple weave. Equivalent planar devices and single-pixel fiber structures are also fabricated. The resultant structures are all actuated, and current-voltage data is obtained for individual pixels using a source meter. Electroluminescence spectra are collected under tension using a UV-NIR spectrometer. The performance of the fiber devices is then compared to its planar analogues. Future directions for investigation are also proposed.

  8. Fabrication of LED full-color display matrix with small pixel

    NASA Astrophysics Data System (ADS)

    Li, Jing; Xue, Bin; Yang, Hua; Liu, Lili; Xie, Haizhong; Pei, Yanrong; Lu, Pengzhi; Wang, Guohong; Wang, Junxi; Li, Jinmin

    2015-09-01

    With the development in material growth, device fabrication and packaging of LEDs, emission spectral of LED is able to cover the visible spectrum. In addition to the well-known lighting applications of LED, display is also one of the important applications of LED. In contrast with LCD, LEDs display has better contrast ratio, higher response rate, etc., which makes LEDs along with other self-illumination technologies an ideal candidate in making display panel. With the popularization of HD and Ultra HD standard, display panel with better image quality is needed. The number of pixels of the panel needs to be increased and the size of each pixel needs to be minimized. In this paper, we prepared a LED full-color display panel based on a 32×32 LED matrix with typical pixel size of 0.5mm. LED full-color display array with small pixel was obtained by mounting red LEDs, green LEDs and blue LEDs directly onto an isolating substrate such as sapphire . In addition, the substrate has metalized pads and connection before the matrix was connected to control unit. The control line and the column data line are prepared on the substrate, and there is an effective electrical insulation layers between them. The isolation layers consists of a SiO2 layer of 1000nm and polyimide layer of 3000nm. Polyimide as an important electrical insulating layer, we study some properties of it, such as :PI amination rate as a function of the curing temperature, PI resistivity as a function of the curing temperature and the punction electric field intensity of PI as a function of the film thickness of PI.

  9. CMOS VLSI Active-Pixel Sensor for Tracking

    NASA Technical Reports Server (NTRS)

    Pain, Bedabrata; Sun, Chao; Yang, Guang; Heynssens, Julie

    2004-01-01

    An architecture for a proposed active-pixel sensor (APS) and a design to implement the architecture in a complementary metal oxide semiconductor (CMOS) very-large-scale integrated (VLSI) circuit provide for some advanced features that are expected to be especially desirable for tracking pointlike features of stars. The architecture would also make this APS suitable for robotic- vision and general pointing and tracking applications. CMOS imagers in general are well suited for pointing and tracking because they can be configured for random access to selected pixels and to provide readout from windows of interest within their fields of view. However, until now, the architectures of CMOS imagers have not supported multiwindow operation or low-noise data collection. Moreover, smearing and motion artifacts in collected images have made prior CMOS imagers unsuitable for tracking applications. The proposed CMOS imager (see figure) would include an array of 1,024 by 1,024 pixels containing high-performance photodiode-based APS circuitry. The pixel pitch would be 9 m. The operations of the pixel circuits would be sequenced and otherwise controlled by an on-chip timing and control block, which would enable the collection of image data, during a single frame period, from either the full frame (that is, all 1,024 1,024 pixels) or from within as many as 8 different arbitrarily placed windows as large as 8 by 8 pixels each. A typical prior CMOS APS operates in a row-at-a-time ( grolling-shutter h) readout mode, which gives rise to exposure skew. In contrast, the proposed APS would operate in a sample-first/readlater mode, suppressing rolling-shutter effects. In this mode, the analog readout signals from the pixels corresponding to the windows of the interest (which windows, in the star-tracking application, would presumably contain guide stars) would be sampled rapidly by routing them through a programmable diagonal switch array to an on-chip parallel analog memory array. The

  10. Active pixel sensor pixel having a photodetector whose output is coupled to an output transistor gate

    NASA Technical Reports Server (NTRS)

    Fossum, Eric R. (Inventor); Nakamura, Junichi (Inventor); Kemeny, Sabrina E. (Inventor)

    2005-01-01

    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. A Simple Floating Gate (SFG) pixel structure could also be employed in the imager to provide a non-destructive readout and smaller pixel sizes.

  11. A CMOS Active Pixel Sensor for Charged Particle Detection

    SciTech Connect

    Matis, Howard S.; Bieser, Fred; Kleinfelder, Stuart; Rai, Gulshan; Retiere, Fabrice; Ritter, Hans George; Singh, Kunal; Wurzel, Samuel E.; Wieman, Howard; Yamamoto, Eugene

    2002-12-02

    Active Pixel Sensor (APS) technology has shown promise for next-generation vertex detectors. This paper discusses the design and testing of two generations of APS chips. Both are arrays of 128 by 128 pixels, each 20 by 20 {micro}m. Each array is divided into sub-arrays in which different sensor structures (4 in the first version and 16 in the second) and/or readout circuits are employed. Measurements of several of these structures under Fe{sup 55} exposure are reported. The sensors have also been irradiated by 55 MeV protons to test for radiation damage. The radiation increased the noise and reduced the signal. The noise can be explained by shot noise from the increased leakage current and the reduction in signal is due to charge being trapped in the epi layer. Nevertheless, the radiation effect is small for the expected exposures at RHIC and RHIC II. Finally, we describe our concept for mechanically supporting a thin silicon wafer in an actual detector.

  12. Evaluation of a single-pixel one-transistor active pixel sensor for fingerprint imaging

    NASA Astrophysics Data System (ADS)

    Xu, Man; Ou, Hai; Chen, Jun; Wang, Kai

    2015-08-01

    Since it first appeared in iPhone 5S in 2013, fingerprint identification (ID) has rapidly gained popularity among consumers. Current fingerprint-enabled smartphones unanimously consists of a discrete sensor to perform fingerprint ID. This architecture not only incurs higher material and manufacturing cost, but also provides only static identification and limited authentication. Hence as the demand for a thinner, lighter, and more secure handset grows, we propose a novel pixel architecture that is a photosensitive device embedded in a display pixel and detects the reflected light from the finger touch for high resolution, high fidelity and dynamic biometrics. To this purpose, an amorphous silicon (a-Si:H) dual-gate photo TFT working in both fingerprint-imaging mode and display-driving mode will be developed.

  13. Monolithic active pixel radiation detector with shielding techniques

    DOEpatents

    Deptuch, Grzegorz W.

    2016-09-06

    A monolithic active pixel radiation detector including a method of fabricating thereof. The disclosed radiation detector can include a substrate comprising a silicon layer upon which electronics are configured. A plurality of channels can be formed on the silicon layer, wherein the plurality of channels are connected to sources of signals located in a bulk part of the substrate, and wherein the signals flow through electrically conducting vias established in an isolation oxide on the substrate. One or more nested wells can be configured from the substrate, wherein the nested wells assist in collecting charge carriers released in interaction with radiation and wherein the nested wells further separate the electronics from the sensing portion of the detector substrate. The detector can also be configured according to a thick SOA method of fabrication.

  14. Active pixel sensor having intra-pixel charge transfer with analog-to-digital converter

    NASA Technical Reports Server (NTRS)

    Fossum, Eric R. (Inventor); Mendis, Sunetra K. (Inventor); Pain, Bedabrata (Inventor); Nixon, Robert H. (Inventor); Zhou, Zhimin (Inventor)

    2003-01-01

    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, a readout circuit including at least an output field effect transistor formed in the substrate, and a charge coupled device section formed on the substrate adjacent the photogate having a sensing node connected to the output transistor and at least one charge coupled device stage for transferring charge from the underlying portion of the substrate to the sensing node and an analog-to-digital converter formed in the substrate connected to the output of the readout circuit.

  15. Active pixel sensor having intra-pixel charge transfer with analog-to-digital converter

    NASA Technical Reports Server (NTRS)

    Fossum, Eric R. (Inventor); Mendis, Sunetra K. (Inventor); Pain, Bedabrata (Inventor); Nixon, Robert H. (Inventor); Zhou, Zhimin (Inventor)

    2000-01-01

    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, a readout circuit including at least an output field effect transistor formed in the substrate, and a charge coupled device section formed on the substrate adjacent the photogate having a sensing node connected to the output transistor and at least one charge coupled device stage for transferring charge from the underlying portion of the substrate to the sensing node and an analog-to-digital converter formed in the substrate connected to the output of the readout circuit.

  16. Active pixel as dosimetric device for interventional radiology

    NASA Astrophysics Data System (ADS)

    Servoli, L.; Baldaccini, F.; Biasini, M.; Checcucci, B.; Chiocchini, S.; Cicioni, R.; Conti, E.; Di Lorenzo, R.; Dipilato, A. C.; Esposito, A.; Fanó, L.; Paolucci, M.; Passeri, D.; Pentiricci, A.; Placidi, P.

    2013-08-01

    Interventional Radiology (IR) is a subspecialty of radiology comprehensive of all minimally invasive diagnostic and therapeutic procedures performed using radiological devices to obtain image guidance. The interventional procedures are potentially harmful for interventional radiologists and medical staff due to the X-ray diffusion by the patient's body. The characteristic energy range of the diffused photons spans few tens of keV. In this work we will present a proposal for a new X-ray sensing element in the energy range of interest for IR procedures. The sensing element will then be assembled in a dosimeter prototype, capable of real-time measurement, packaged in a small form-factor, with wireless communication and no external power supply to be used for individual operators dosimetry for IR procedures. For the sensor, which is the heart of the system, we considered three different Active Pixel Sensors (APS). They have shown a good capability as single X-ray photon detectors, up to several tens keV photon energy. Two dosimetric quantities have been considered, the number of detected photons and the measured energy deposition. Both observables have a linear dependence with the dose, as measured by commercial dosimeters. The uncertainties in the measurement are dominated by statistic and can be pushed at ˜5% for all the sensors under test.

  17. Development of a super B-factory monolithic active pixel detector—the Continuous Acquisition Pixel (CAP) prototypes

    NASA Astrophysics Data System (ADS)

    Varner, G.; Barbero, M.; Bozek, A.; Browder, T.; Fang, F.; Hazumi, M.; Igarashi, A.; Iwaida, S.; Kennedy, J.; Kent, N.; Olsen, S.; Palka, H.; Rosen, M.; Ruckman, L.; Stanic, S.; Trabelsi, K.; Tsuboyama, T.; Uchida, K.

    2005-04-01

    Over the last few years great progress has been made in the technological development of Monolithic Active Pixel Sensors (MAPS) such that upgrades to existing vertex detectors using this technology are now actively being considered. Future vertex detection at an upgraded KEK-B factory, already the highest luminosity collider in the world, will require a detector technology capable of withstanding the increased track densities and larger radiation exposures. Near the beam pipe the current silicon strip detectors have projected occupancies in excess of 100%. Deep sub-micron MAPS look very promising to address this problem. In the context of an upgrade to the Belle vertex detector, the major obstacles to realizing such a device have been concerns about radiation hardness and readout speed. Two prototypes implemented in the TSMC 0.35 μm process have been developed to address these issues. Denoted the Continuous Acquisition Pixel, or CAP, the two variants of this architecture are distinguished in that CAP2 includes an 8-deep sampling pipeline within each 22.5 μm 2 pixel. Preliminary test results and remaining R&D issues are presented.

  18. 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.

  19. Active-Pixel Image Sensor With Analog-To-Digital Converters

    NASA Technical Reports Server (NTRS)

    Fossum, Eric R.; Mendis, Sunetra K.; Pain, Bedabrata; Nixon, Robert H.

    1995-01-01

    Proposed single-chip integrated-circuit image sensor contains 128 x 128 array of active pixel sensors at 50-micrometer pitch. Output terminals of all pixels in each given column connected to analog-to-digital (A/D) converter located at bottom of column. Pixels scanned in semiparallel fashion, one row at time; during time allocated to scanning row, outputs of all active pixel sensors in row fed to respective A/D converters. Design of chip based on complementary metal oxide semiconductor (CMOS) technology, and individual circuit elements fabricated according to 2-micrometer CMOS design rules. Active pixel sensors designed to operate at video rate of 30 frames/second, even at low light levels. A/D scheme based on first-order Sigma-Delta modulation.

  20. X-ray imaging characterization of active edge silicon pixel sensors

    NASA Astrophysics Data System (ADS)

    Ponchut, C.; Ruat, M.; Kalliopuska, J.

    2014-05-01

    The aim of this work was the experimental characterization of edge effects in active-edge silicon pixel sensors, in the frame of X-ray pixel detectors developments for synchrotron experiments. We produced a set of active edge pixel sensors with 300 to 500 μm thickness, edge widths ranging from 100 μm to 150 μm, and n or p pixel contact types. The sensors with 256 × 256 pixels and 55 × 55 μm2 pixel pitch were then bump-bonded to Timepix readout chips for X-ray imaging measurements. The reduced edge widths makes the edge pixels more sensitive to the electrical field distribution at the sensor boundaries. We characterized this effect by mapping the spatial response of the sensor edges with a finely focused X-ray synchrotron beam. One of the samples showed a distortion-free response on all four edges, whereas others showed variable degrees of distortions extending at maximum to 300 micron from the sensor edge. An application of active edge pixel sensors to coherent diffraction imaging with synchrotron beams is described.

  1. Characteristics of Monolithically Integrated InGaAs Active Pixel Image Array

    NASA Technical Reports Server (NTRS)

    Kim, Q.; Cunningham, T. J.; Pain, B.; Lange, M. J.; Olsen, G. H.

    1999-01-01

    Switching and amplifying characteristics of a newly developed monolithic InGaAs Active Pixel Imager Array are presented. The sensor array is fabricated from InGaAs material epitaxially deposited on an InP substrate.

  2. Center of mass detection via an active pixel sensor

    NASA Technical Reports Server (NTRS)

    Yadid-Pecht, Orly (Inventor); Minch, Brad (Inventor); Pain, Bedabrara (Inventor); Fossum, Eric (Inventor)

    2006-01-01

    An imaging system for identifying the location of the center of mass (COM) in an image. In one aspect, an imaging system includes a plurality of photosensitive elements arranged in a matrix. A center of mass circuit coupled to the photosensitive elements includes a resistive network and a normalization circuit including at least one bipolar transistor. The center of mass circuit identifies a center of mass location in the matrix and includes: a row circuit, where the row circuit identifies a center of mass row value in each row of the matrix and identifies a row intensity for each row; a horizontal circuit, where the horizontal circuit identifies a center of mass horizontal value; and a vertical circuit, where the vertical circuit identifies a center of mass vertical value. The horizontal and vertical center of mass values indicate the coordinates of the center of mass location for the image.

  3. Center of mass detection via an active pixel sensor

    NASA Technical Reports Server (NTRS)

    Yadid-Pecht, Orly (Inventor); Minch, Brad (Inventor); Pain, Bedabrata (Inventor); Fossum, Eric (Inventor)

    2005-01-01

    An imaging system for identifying the location of the center of mass (COM) in an image. In one aspect, an imaging system includes a plurality of photosensitive elements arranged in a matrix. A center of mass circuit coupled to the photosensitive elements includes a resistive network and a normalization circuit including at least one bipolar transistor. The center of mass circuit identifies a center of mass location in the matrix and includes: a row circuit, where the row circuit identifies a center of mass row value in each row of the matrix and identifies a row intensity for each row; a horizontal circuit, where the horizontal circuit identifies a center of mass horizontal value; and a vertical circuit, where the vertical circuit identifies a center of mass vertical value. The horizontal and vertical center of mass values indicate the coordinates of the center of mass location for the image.

  4. Center of mass detection via an active pixel sensor

    NASA Technical Reports Server (NTRS)

    Yadid-Pecht, Orly (Inventor); Minch, Brad (Inventor); Pain, Bedabrata (Inventor); Fossum, Eric (Inventor)

    2002-01-01

    An imaging system for identifying the location of the center of mass (COM) in an image. In one aspect, an imaging system includes a plurality of photosensitive elements arranged in a matrix. A center of mass circuit coupled to the photosensitive elements includes a resistive network and a normalization circuit including at least one bipolar transistor. The center of mass circuit identifies a center of mass location in the matrix and includes: a row circuit, where the row circuit identifies a center of mass row value in each row of the matrix and identifies a row intensity for each row; a horizontal circuit, where the horizontal circuit identifies a center of mass horizontal value; and a vertical circuit, where the vertical circuit identifies a center of mass vertical value. The horizontal and vertical center of mass values indicate the coordinates of the center of mass location for the image.

  5. Jet-Printed Active-Matrix Backplanes and Electrophoretic Displays

    NASA Astrophysics Data System (ADS)

    Daniel, Jurgen; Arias, Ana Claudia; Wong, William; Lujan, Rene; Ready, Steve; Krusor, Brent; Street, Robert

    2007-03-01

    The fabrication of large-area electronics, such as active-matrix pixel circuits in flat-panel displays, is becoming increasingly challenging. Particularly for applications such as electronic paper, flexibility of the display and fabrication at extremely low cost is important. Therefore, novel fabrication methods have to be explored. We have developed jet-printing technology to fabricate active-matrix backplanes for paper-like electrophoretic displays. In three approaches we implement several stages of evolution of the printing technology. First, the photolithographic patterning of photoresist used in conventional fabrication is replaced by digital printing of a wax etch mask. Second, the amorphous silicon semiconductor for the thin-film-transistors is replaced with a printed organic semiconductor. Third, the active-matrix pixel circuit is fabricated in an all-additive printing process. In order to test our backplanes we are developing electrophoretic display media. The media is based on microfabricated cell-structures which contain the electrophoretic ink. Particularly for flexible displays, the cells have to be individually sealed and several methods are being explored.

  6. Memory based active contour algorithm using pixel-level classified images for colon crypt segmentation.

    PubMed

    Cohen, Assaf; Rivlin, Ehud; Shimshoni, Ilan; Sabo, Edmond

    2015-07-01

    In this paper, we introduce a novel method for detection and segmentation of crypts in colon biopsies. Most of the approaches proposed in the literature try to segment the crypts using only the biopsy image without understanding the meaning of each pixel. The proposed method differs in that we segment the crypts using an automatically generated pixel-level classification image of the original biopsy image and handle the artifacts due to the sectioning process and variance in color, shape and size of the crypts. The biopsy image pixels are classified to nuclei, immune system, lumen, cytoplasm, stroma and goblet cells. The crypts are then segmented using a novel active contour approach, where the external force is determined by the semantics of each pixel and the model of the crypt. The active contour is applied for every lumen candidate detected using the pixel-level classification. Finally, a false positive crypt elimination process is performed to remove segmentation errors. This is done by measuring their adherence to the crypt model using the pixel level classification results. The method was tested on 54 biopsy images containing 4944 healthy and 2236 cancerous crypts, resulting in 87% detection of the crypts with 9% of false positive segments (segments that do not represent a crypt). The segmentation accuracy of the true positive segments is 96%.

  7. Recent progress in the development of a B-factory monolithic active pixel detector

    NASA Astrophysics Data System (ADS)

    Stanič, S.; Aihara, H.; Barbero, M.; Bozek, A.; Browder, T.; Hazumi, M.; Kennedy, J.; Kent, N.; Olsen, S.; Palka, H.; Rosen, M.; Ruckman, L.; Trabelsi, K.; Tsuboyama, T.; Uchida, K.; Varner, G.; Yang, Q.

    2006-11-01

    Due to the need for precise vertexing at future higher luminosity B-factories with the expectedly increasing track densities and radiation exposures, upgrade of present silicon strip detectors with thin, radiation resistant pixel detectors is highly desired. Considerable progress in the technological development of thin CMOS based Monolithic Active Pixel Sensors (MAPS) in the last years makes them a realistic upgrade option and the feasibility studies of their application in Belle are actively pursued. The most serious concerns are their radiation hardness and their read-out speed. To address them, several prototypes denoted as Continuous Acquisition Pixel (CAP) sensors have been developed and tested. The latest of the CAP sensor prototypes is CAP3, designed in the TSMC 0.25 μm process with a 5-deep sample pair pipeline in each pixel. A setup with several CAP3 sensors will be used to assess the performance of a full scale pixel read-out system running at realistic read-out speed. The results and plans for the next stages of R&D towards a full Pixel Vertex Detector (PVD) are presented.

  8. Pixel-level multisensor image fusion based on matrix completion and robust principal component analysis

    NASA Astrophysics Data System (ADS)

    Wang, Zhuozheng; Deller, J. R.; Fleet, Blair D.

    2016-01-01

    Acquired digital images are often corrupted by a lack of camera focus, faulty illumination, or missing data. An algorithm is presented for fusion of multiple corrupted images of a scene using the lifting wavelet transform. The method employs adaptive fusion arithmetic based on matrix completion and self-adaptive regional variance estimation. Characteristics of the wavelet coefficients are used to adaptively select fusion rules. Robust principal component analysis is applied to low-frequency image components, and regional variance estimation is applied to high-frequency components. Experiments reveal that the method is effective for multifocus, visible-light, and infrared image fusion. Compared with traditional algorithms, the new algorithm not only increases the amount of preserved information and clarity but also improves robustness.

  9. A CMOS Energy Harvesting and Imaging (EHI) Active Pixel Sensor (APS) Imager for Retinal Prosthesis.

    PubMed

    Ay, S U

    2011-12-01

    A CMOS image sensor capable of imaging and energy harvesting on same focal plane is presented for retinal prosthesis. The energy harvesting and imaging (EHI) active pixel sensor (APS) imager was designed, fabricated, and tested in a standard 0.5 μm CMOS process. It has 54 × 50 array of 21 × 21 μm(2) EHI pixels, 10-bit supply boosted (SB) SAR ADC, and charge pump circuits consuming only 14.25 μW from 1.2 V and running at 7.4 frames per second. The supply boosting technique (SBT) is used in an analog signal chain of the EHI imager. Harvested solar energy on focal plane is stored on an off-chip capacitor with the help of a charge pump circuit with better than 70% efficiency. Energy harvesting efficiency of the EHI pixel was measured at different light levels. It was 9.4% while producing 0.41 V open circuit voltage. The EHI imager delivers 3.35 μW of power was delivered to a resistive load at maximum power point operation. The measured pixel array figure of merit (FoM) was 1.32 pW/frame/pixel while imager figure of merit (iFoM) including whole chip power consumption was 696 fJ/pixel/code for the EHI imager.

  10. The MuPix high voltage monolithic active pixel sensor for the Mu3e experiment

    NASA Astrophysics Data System (ADS)

    Augustin, H.; Berger, N.; Bravar, S.; Corrodi, S.; Damyanova, A.; Förster, F.; Gredig, R.; Herkert, A.; Huang, Q.; Huth, L.; Kiehn, M.; Kozlinskiy, A.; Maldaner, S.; Perić, I.; Philipp, R.; Robmann, P.; Schöning, A.; Shrestha, S.; vom Bruch, D.; Weber, T.; Wiedner, D.

    2015-03-01

    Mu3e is a novel experiment searching for charged lepton flavor violation in the rare decay μ → eee. In order to reduce background by up to 16 orders of magnitude, decay vertex position, decay time and particle momenta have to be measured precisely. A pixel tracker based on 50 μm thin high voltage monolithic active pixel sensors (HV-MAPS) in a magnetic field will deliver precise vertex and momentum information. Test beam results like an excellent efficiency of >99.5% and a time resolution of better than 16.6 ns obtained with the MuPix HV-MAPS chip developed for the Mu3e pixel tracker are presented.

  11. 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

  12. Heavily irradiated N-in-p thin planar pixel sensors with and without active edges

    NASA Astrophysics Data System (ADS)

    Terzo, S.; Andricek, L.; Macchiolo, A.; Moser, H. G.; Nisius, R.; Richter, R. H.; Weigell, P.

    2014-05-01

    We present the results of the characterization of silicon pixel modules employing n-in-p planar sensors with an active thickness of 150 μm, produced at MPP/HLL, and 100-200 μm thin active edge sensor devices, produced at VTT in Finland. These thin sensors are designed as candidates for the ATLAS pixel detector upgrade to be operated at the HL-LHC, as they ensure radiation hardness at high fluences. They are interconnected to the ATLAS FE-I3 and FE-I4 read-out chips. Moreover, the n-in-p technology only requires a single side processing and thereby it is a cost-effective alternative to the n-in-n pixel technology presently employed in the LHC experiments. High precision beam test measurements of the hit efficiency have been performed on these devices both at the CERN SpS and at DESY, Hamburg. We studied the behavior of these sensors at different bias voltages and different beam incident angles up to the maximum one expected for the new Insertable B-Layer of ATLAS and for HL-LHC detectors. Results obtained with 150 μm thin sensors, assembled with the new ATLAS FE-I4 chip and irradiated up to a fluence of 4 × 1015 neq/cm2, show that they are excellent candidates for larger radii of the silicon pixel tracker in the upgrade of the ATLAS detector at HL-LHC. In addition, the active edge technology of the VTT devices maximizes the active area of the sensor and reduces the material budget to suit the requirements for the innermost layers. The edge pixel performance of VTT modules has been investigated at beam test experiments and the analysis after irradiation up to a fluence of 5 × 1015 neq/cm2 has been performed using radioactive sources in the laboratory.

  13. High voltage protection in active matrix flat-panel imagers

    NASA Astrophysics Data System (ADS)

    Lehnert, Joerg; Zhao, Wei

    2006-03-01

    Various direct and indirect active matrix flat-panel imagers (AMFPI) are being investigated for x-ray imaging. In both direct AMFPI and indirect AMFPI with avalanche gain, a bias potential up to several thousand volts is required to operate the photoconductor. Under the condition of a large amount of radiation exposure between subsequent readout, a potential >80 V could appear across the amorphous silicon (a-Si) thin film transistor (TFT) and cause permanent damage. The purpose of this paper is to investigate a simple pixel design for high voltage protection. The pixel electrode acts as an additional gate for the top channel of an a-Si TFT to drain excess image charge from the pixel electrode until an equilibrium is reached where the TFT channel current equals the detector signal current at a predetermined safe maximum value V Pmax for the pixel potential. This "dual-gate" TFT structure without additional protective device simplifies the TFT array design and improves yield. However special care is required to understand the characteristics of both the top and the bottom gates to ensure sufficient detector dynamic range as well as reliable high voltage protection. A physical model for dual-gate a-Si TFTs was developed and device parameters were determined by fitting the model to measured characteristics from a dual-gate TFT array. Our results showed that compared to the bottom (normal) gate, the protective gate has a shallower transfer characteristics (i.e. channel current as a function of gate voltage) due to a higher density of states in the top interface. Nevertheless it provides adequate protection of the TFT with V Pmax of ~40 V for typical radiographic exposures.

  14. A Design of a New Column-Parallel Analog-to-Digital Converter Flash for Monolithic Active Pixel Sensor.

    PubMed

    Chakir, Mostafa; Akhamal, Hicham; Qjidaa, Hassan

    2017-01-01

    The CMOS Monolithic Active Pixel Sensor (MAPS) for the International Linear Collider (ILC) vertex detector (VXD) expresses stringent requirements on their analog readout electronics, specifically on the analog-to-digital converter (ADC). This paper concerns designing and optimizing a new architecture of a low power, high speed, and small-area 4-bit column-parallel ADC Flash. Later in this study, we propose to interpose an S/H block in the converter. This integration of S/H block increases the sensitiveness of the converter to the very small amplitude of the input signal from the sensor and provides a sufficient time to the converter to be able to code the input signal. This ADC is developed in 0.18 μm CMOS process with a pixel pitch of 35 μm. The proposed ADC responds to the constraints of power dissipation, size, and speed for the MAPS composed of a matrix of 64 rows and 48 columns where each column ADC covers a small area of 35 × 336.76 μm(2). The proposed ADC consumes low power at a 1.8 V supply and 100 MS/s sampling rate with dynamic range of 125 mV. Its DNL and INL are 0.0812/-0.0787 LSB and 0.0811/-0.0787 LSB, respectively. Furthermore, this ADC achieves a high speed more than 5 GHz.

  15. Characteristics of Monolithically Integrated InGaAs Active Pixel Imager Array

    NASA Technical Reports Server (NTRS)

    Kim, Q.; Cunningham, T. J.; Pain, B.; Lange, M. J.; Olsen, G. H.

    2000-01-01

    Switching and amplifying characteristics of a newly developed monolithic InGaAs Active Pixel Imager Array are presented. The sensor array is fabricated from InGaAs material epitaxially deposited on an InP substrate. It consists of an InGaAs photodiode connected to InP depletion-mode junction field effect transistors (JFETs) for low leakage, low power, and fast control of circuit signal amplifying, buffering, selection, and reset. This monolithically integrated active pixel sensor configuration eliminates the need for hybridization with silicon multiplexer. In addition, the configuration allows the sensor to be front illuminated, making it sensitive to visible as well as near infrared signal radiation. Adapting the existing 1.55 micrometer fiber optical communication technology, this integration will be an ideal system of optoelectronic integration for dual band (Visible/IR) applications near room temperature, for use in atmospheric gas sensing in space, and for target identification on earth. In this paper, two different types of small 4 x 1 test arrays will be described. The effectiveness of switching and amplifying circuits will be discussed in terms of circuit effectiveness (leakage, operating frequency, and temperature) in preparation for the second phase demonstration of integrated, two-dimensional monolithic InGaAs active pixel sensor arrays for applications in transportable shipboard surveillance, night vision, and emission spectroscopy.

  16. Development of active edge pixel sensors and four-side buttable modules using vertical integration technologies

    NASA Astrophysics Data System (ADS)

    Macchiolo, A.; Andricek, L.; Moser, H.-G.; Nisius, R.; Richter, R. H.; Terzo, S.; Weigell, P.

    2014-11-01

    We present an R&D activity focused on the development of novel modules for the upgrade of the ATLAS pixel system at the High Luminosity LHC (HL-LHC). The modules consist of n-in-p pixel sensors, 100 or 200 μm thick, produced at VTT (Finland) with an active edge technology, which considerably reduces the dead area at the periphery of the device. The sensors are interconnected with solder bump-bonding to the ATLAS FE-I3 and FE-I4 read-out chips, and characterised with radioactive sources and beam tests at the CERN-SPS and DESY. The results of these measurements will be discussed for devices before and after irradiation up to a fluence of 5 ×1015neq /cm2. We will also report on the R&D activity to obtain Inter Chip Vias (ICVs) on the ATLAS read-out chip in collaboration with the Fraunhofer Institute EMFT. This step is meant to prove the feasibility of the signal transport to the newly created readout pads on the backside of the chips allowing for four side buttable devices without the presently used cantilever for wire bonding. The read-out chips with ICVs will be interconnected to thin pixel sensors, 75 μm and 150 μm thick, with the Solid Liquid Interdiffusion (SLID) technology, which is an alternative to the standard solder bump-bonding.

  17. Three-dimensional cascaded system analysis of a 50 µm pixel pitch wafer-scale CMOS active pixel sensor x-ray detector for digital breast tomosynthesis

    NASA Astrophysics Data System (ADS)

    Zhao, C.; Vassiljev, N.; Konstantinidis, A. C.; Speller, R. D.; Kanicki, J.

    2017-03-01

    High-resolution, low-noise x-ray detectors based on the complementary metal-oxide-semiconductor (CMOS) active pixel sensor (APS) technology have been developed and proposed for digital breast tomosynthesis (DBT). In this study, we evaluated the three-dimensional (3D) imaging performance of a 50 µm pixel pitch CMOS APS x-ray detector named DynAMITe (Dynamic Range Adjustable for Medical Imaging Technology). The two-dimensional (2D) angle-dependent modulation transfer function (MTF), normalized noise power spectrum (NNPS), and detective quantum efficiency (DQE) were experimentally characterized and modeled using the cascaded system analysis at oblique incident angles up to 30°. The cascaded system model was extended to the 3D spatial frequency space in combination with the filtered back-projection (FBP) reconstruction method to calculate the 3D and in-plane MTF, NNPS and DQE parameters. The results demonstrate that the beam obliquity blurs the 2D MTF and DQE in the high spatial frequency range. However, this effect can be eliminated after FBP image reconstruction. In addition, impacts of the image acquisition geometry and detector parameters were evaluated using the 3D cascaded system analysis for DBT. The result shows that a wider projection angle range (e.g.  ±30°) improves the low spatial frequency (below 5 mm‑1) performance of the CMOS APS detector. In addition, to maintain a high spatial resolution for DBT, a focal spot size of smaller than 0.3 mm should be used. Theoretical analysis suggests that a pixelated scintillator in combination with the 50 µm pixel pitch CMOS APS detector could further improve the 3D image resolution. Finally, the 3D imaging performance of the CMOS APS and an indirect amorphous silicon (a-Si:H) thin-film transistor (TFT) passive pixel sensor (PPS) detector was simulated and compared.

  18. Three-dimensional cascaded system analysis of a 50 µm pixel pitch wafer-scale CMOS active pixel sensor x-ray detector for digital breast tomosynthesis.

    PubMed

    Zhao, C; Vassiljev, N; Konstantinidis, A C; Speller, R D; Kanicki, J

    2017-03-07

    High-resolution, low-noise x-ray detectors based on the complementary metal-oxide-semiconductor (CMOS) active pixel sensor (APS) technology have been developed and proposed for digital breast tomosynthesis (DBT). In this study, we evaluated the three-dimensional (3D) imaging performance of a 50 µm pixel pitch CMOS APS x-ray detector named DynAMITe (Dynamic Range Adjustable for Medical Imaging Technology). The two-dimensional (2D) angle-dependent modulation transfer function (MTF), normalized noise power spectrum (NNPS), and detective quantum efficiency (DQE) were experimentally characterized and modeled using the cascaded system analysis at oblique incident angles up to 30°. The cascaded system model was extended to the 3D spatial frequency space in combination with the filtered back-projection (FBP) reconstruction method to calculate the 3D and in-plane MTF, NNPS and DQE parameters. The results demonstrate that the beam obliquity blurs the 2D MTF and DQE in the high spatial frequency range. However, this effect can be eliminated after FBP image reconstruction. In addition, impacts of the image acquisition geometry and detector parameters were evaluated using the 3D cascaded system analysis for DBT. The result shows that a wider projection angle range (e.g.  ±30°) improves the low spatial frequency (below 5 mm(-1)) performance of the CMOS APS detector. In addition, to maintain a high spatial resolution for DBT, a focal spot size of smaller than 0.3 mm should be used. Theoretical analysis suggests that a pixelated scintillator in combination with the 50 µm pixel pitch CMOS APS detector could further improve the 3D image resolution. Finally, the 3D imaging performance of the CMOS APS and an indirect amorphous silicon (a-Si:H) thin-film transistor (TFT) passive pixel sensor (PPS) detector was simulated and compared.

  19. Curved Ferroelectric Liquid Crystal Matrix Displays Driven by Field-Sequential-Color and Active-Matrix Techniques

    NASA Astrophysics Data System (ADS)

    Fujikake, Hideo; Sato, Hiroto; Murashige, Takeshi; Fujisaki, Yoshihide; Kurita, Taiichiro; Furukawa, Tadahiro; Sato, Fumio

    This paper describes a curved field-sequential-color matrix display using fast-response ferroelectric liquid crystal. Black matrix and transparent electrode patterns were formed on a thin plastic substrate by a transfer method from a glass substrate. While a composite film of liquid crystal and micro-polymers of walls and fibers was formed between the flexible substrates by printing, laminating and curing processes of a solution of monomers and liquid crystal, the mechanical stability was enhanced by use of multi-functional monomers to form large display panels. The image pixels of the matrix panel were driven by an active matrix scheme using an external switch transistor array at a frequency of 180 Hz for intermittent three-primary-color backlight illumination. The flexible A4-paper-sized color display with 24 × 16 pixels and 60 Hz field frequency was demonstrated by illuminating it with sequential three-primary-color lights from light-emitting diodes of the backlight. Our display system is useful in various information displays because of its freedom of setting and location.

  20. Performance of a novel wafer scale CMOS active pixel sensor for bio-medical imaging

    NASA Astrophysics Data System (ADS)

    Esposito, M.; Anaxagoras, T.; Konstantinidis, A. C.; Zheng, Y.; Speller, R. D.; Evans, P. M.; Allinson, N. M.; Wells, K.

    2014-07-01

    Recently CMOS active pixels sensors (APSs) have become a valuable alternative to amorphous silicon and selenium flat panel imagers (FPIs) in bio-medical imaging applications. CMOS APSs can now be scaled up to the standard 20 cm diameter wafer size by means of a reticle stitching block process. However, despite wafer scale CMOS APS being monolithic, sources of non-uniformity of response and regional variations can persist representing a significant challenge for wafer scale sensor response. Non-uniformity of stitched sensors can arise from a number of factors related to the manufacturing process, including variation of amplification, variation between readout components, wafer defects and process variations across the wafer due to manufacturing processes. This paper reports on an investigation into the spatial non-uniformity and regional variations of a wafer scale stitched CMOS APS. For the first time a per-pixel analysis of the electro-optical performance of a wafer CMOS APS is presented, to address inhomogeneity issues arising from the stitching techniques used to manufacture wafer scale sensors. A complete model of the signal generation in the pixel array has been provided and proved capable of accounting for noise and gain variations across the pixel array. This novel analysis leads to readout noise and conversion gain being evaluated at pixel level, stitching block level and in regions of interest, resulting in a coefficient of variation ⩽1.9%. The uniformity of the image quality performance has been further investigated in a typical x-ray application, i.e. mammography, showing a uniformity in terms of CNR among the highest when compared with mammography detectors commonly used in clinical practice. Finally, in order to compare the detection capability of this novel APS with the technology currently used (i.e. FPIs), theoretical evaluation of the detection quantum efficiency (DQE) at zero-frequency has been performed, resulting in a higher DQE for this

  1. Performance of a novel wafer scale CMOS active pixel sensor for bio-medical imaging.

    PubMed

    Esposito, M; Anaxagoras, T; Konstantinidis, A C; Zheng, Y; Speller, R D; Evans, P M; Allinson, N M; Wells, K

    2014-07-07

    Recently CMOS active pixels sensors (APSs) have become a valuable alternative to amorphous silicon and selenium flat panel imagers (FPIs) in bio-medical imaging applications. CMOS APSs can now be scaled up to the standard 20 cm diameter wafer size by means of a reticle stitching block process. However, despite wafer scale CMOS APS being monolithic, sources of non-uniformity of response and regional variations can persist representing a significant challenge for wafer scale sensor response. Non-uniformity of stitched sensors can arise from a number of factors related to the manufacturing process, including variation of amplification, variation between readout components, wafer defects and process variations across the wafer due to manufacturing processes. This paper reports on an investigation into the spatial non-uniformity and regional variations of a wafer scale stitched CMOS APS. For the first time a per-pixel analysis of the electro-optical performance of a wafer CMOS APS is presented, to address inhomogeneity issues arising from the stitching techniques used to manufacture wafer scale sensors. A complete model of the signal generation in the pixel array has been provided and proved capable of accounting for noise and gain variations across the pixel array. This novel analysis leads to readout noise and conversion gain being evaluated at pixel level, stitching block level and in regions of interest, resulting in a coefficient of variation ⩽1.9%. The uniformity of the image quality performance has been further investigated in a typical x-ray application, i.e. mammography, showing a uniformity in terms of CNR among the highest when compared with mammography detectors commonly used in clinical practice. Finally, in order to compare the detection capability of this novel APS with the technology currently used (i.e. FPIs), theoretical evaluation of the detection quantum efficiency (DQE) at zero-frequency has been performed, resulting in a higher DQE for this

  2. Development of a new electronic personal neutron dosemeter using a CMOS active pixel sensor.

    PubMed

    Trocmé, M; Higueret, S; Husson, D; Nourreddine, A; Lê, T D

    2007-01-01

    A CMOS active pixel sensor, originally designed for the tracking of minimum ionising charged particles in high-energy physics, has been recently used for the detection of fast neutrons. Data were taken at the IRSN Cadarache facility with a (241)Am-Be ISO source and a polyethylene radiator. A high-intrinsic efficiency (1.2 x 10(-3)) has been obtained. It is in good agreement with both calculations and a MCNPX Monte Carlo simulation. This experiment paves the way for a fully electronic personal neutron dosemeter.

  3. ALPIDE: the Monolithic Active Pixel Sensor for the ALICE ITS upgrade

    NASA Astrophysics Data System (ADS)

    Šuljić, M.

    2016-11-01

    The upgrade of the ALICE vertex detector, the Inner Tracking System (ITS), is scheduled to be installed during the next long shutdown period (2019-2020) of the CERN Large Hadron Collider (LHC) . The current ITS will be replaced by seven concentric layers of Monolithic Active Pixel Sensors (MAPS) with total active surface of ~10 m2, thus making ALICE the first LHC experiment implementing MAPS detector technology on a large scale. The ALPIDE chip, based on TowerJazz 180 nm CMOS Imaging Process, is being developed for this purpose. A particular process feature, the deep p-well, is exploited so the full CMOS logic can be implemented over the active sensor area without impinging on the deposited charge collection. ALPIDE is implemented on silicon wafers with a high resistivity epitaxial layer. A single chip measures 15 mm by 30 mm and contains half a million pixels distributed in 512 rows and 1024 columns. In-pixel circuitry features amplification, shaping, discrimination and multi-event buffering. The readout is hit driven i.e. only addresses of hit pixels are sent to the periphery. The upgrade of the ITS presents two different sets of requirements for sensors of the inner and of the outer layers due to the significantly different track density, radiation level and active detector surface. The ALPIDE chip fulfils the stringent requirements in both cases. The detection efficiency is higher than 99%, fake-hit probability is orders of magnitude lower than the required 10-6 and spatial resolution within the required 5 μm. This performance is to be maintained even after a total ionising does (TID) of 2.7 Mrad and a non-ionising energy loss (NIEL) fluence of 1.7 × 1013 1 MeV neq/cm2, which is above what is expected during the detector lifetime. Readout rate of 100 kHz is provided and the power density of ALPIDE is less than 40 mW/cm2. This contribution will provide a summary of the ALPIDE features and main test results.

  4. Development of CMOS Active Pixel Image Sensors for Low Cost Commercial Applications

    NASA Technical Reports Server (NTRS)

    Fossum, E.; Gee, R.; Kemeny, S.; Kim, Q.; Mendis, S.; Nakamura, J.; Nixon, R.; Ortiz, M.; Pain, B.; Zhou, Z.; Ackland, B.; Dickinson, A.; Eid, E.; Inglis, D.

    1994-01-01

    This paper describes ongoing research and development of CMOS active pixel image sensors for low cost commercial applications. A number of sensor designs have been fabricated and tested in both p-well and n-well technologies. Major elements in the development of the sensor include on-chip analog signal processing circuits for the reduction of fixed pattern noise, on-chip timing and control circuits and on-chip analog-to-digital conversion (ADC). Recent results and continuing efforts in these areas will be presented.

  5. Development of CMOS Active Pixel Image Sensors for Low Cost Commercial Applications

    NASA Technical Reports Server (NTRS)

    Gee, R.; Kemeny, S.; Kim, Q.; Mendis, S.; Nakamura, J.; Nixon, R.; Ortiz, M.; Pain, B.; Staller, C.; Zhou, Z; Fossum, E.

    1994-01-01

    JPL, under sponsorship from the NASA Office of Advanced Concepts and Technology, has been developing a second-generation solid-state image sensor technology. Charge-coupled devices (CCD) are a well-established first generation image sensor technology. For both commercial and NASA applications, CCDs have numerous shortcomings. In response, the active pixel sensor (APS) technology has been under research. The major advantages of APS technology are the ability to integrate on-chip timing, control, signal-processing and analog-to-digital converter functions, reduced sensitivity to radiation effects, low power operation, and random access readout.

  6. A Design of a New Column-Parallel Analog-to-Digital Converter Flash for Monolithic Active Pixel Sensor

    PubMed Central

    Qjidaa, Hassan

    2017-01-01

    The CMOS Monolithic Active Pixel Sensor (MAPS) for the International Linear Collider (ILC) vertex detector (VXD) expresses stringent requirements on their analog readout electronics, specifically on the analog-to-digital converter (ADC). This paper concerns designing and optimizing a new architecture of a low power, high speed, and small-area 4-bit column-parallel ADC Flash. Later in this study, we propose to interpose an S/H block in the converter. This integration of S/H block increases the sensitiveness of the converter to the very small amplitude of the input signal from the sensor and provides a sufficient time to the converter to be able to code the input signal. This ADC is developed in 0.18 μm CMOS process with a pixel pitch of 35 μm. The proposed ADC responds to the constraints of power dissipation, size, and speed for the MAPS composed of a matrix of 64 rows and 48 columns where each column ADC covers a small area of 35 × 336.76 μm2. The proposed ADC consumes low power at a 1.8 V supply and 100 MS/s sampling rate with dynamic range of 125 mV. Its DNL and INL are 0.0812/−0.0787 LSB and 0.0811/−0.0787 LSB, respectively. Furthermore, this ADC achieves a high speed more than 5 GHz. PMID:28243628

  7. Improved Design of Active Pixel CMOS Sensors for Charged Particle Detection

    SciTech Connect

    Deptuch, Grzegorz

    2007-11-12

    The Department of Energy (DOE) nuclear physics program requires developments in detector instrumentation electronics with improved energy, position and timing resolution, sensitivity, rate capability, stability, dynamic range, and background suppression. The current Phase-I project was focused on analysis of standard-CMOS photogate Active Pixel Sensors (APS) as an efficient solution to this challenge. The advantages of the CMOS APS over traditional hybrid approaches (i.e., separate detection regions bump-bonded to readout circuits) include greatly reduced cost, low power and the potential for vastly larger pixel counts and densities. However, challenges remain in terms of the signal-to-noise ratio (SNR) and readout speed (currently on the order of milliseconds), which is the major problem for this technology. Recent work has shown that the long readout time for photogate APS is due to the presence of (interface) traps at the semiconductor-oxide interface. This Phase-I work yielded useful results in two areas: (a) Advanced three-dimensional (3D) physics-based simulation models and simulation-based analysis of the impact of interface trap density on the transient charge collection characteristics of existing APS structures; and (b) Preliminary analysis of the feasibility of an improved photogate pixel structure (i.e., new APS design) with an induced electric field under the charge collecting electrode to enhance charge collection. Significant effort was dedicated in Phase-I to the critical task of implementing accurate interface trap models in CFDRC's NanoTCAD 3D semiconductor device-physics simulator. This resulted in validation of the new NanoTCAD models and simulation results against experimental (published) data, within the margin of uncertainty associated with obtaining device geometry, material properties, and experimentation details. Analyses of the new, proposed photogate APS design demonstrated several promising trends.

  8. TFT-Based Active Pixel Sensors for Large Area Thermal Neutron Detection

    NASA Astrophysics Data System (ADS)

    Kunnen, George

    Due to diminishing availability of 3He, which is the critical component of neutron detecting proportional counters, large area flexible arrays are being considered as a potential replacement for neutron detection. A large area flexible array, utilizing semiconductors for both charged particle detection and pixel readout, ensures a large detection surface area in a light weight rugged form. Such a neutron detector could be suitable for deployment at ports of entry. The specific approach used in this research, uses a neutron converter layer which captures incident thermal neutrons, and then emits ionizing charged particles. These ionizing particles cause electron-hole pair generation within a single pixel's integrated sensing diode. The resulting charge is then amplified via a low-noise amplifier. This document begins by discussing the current state of the art in neutron detection and the associated challenges. Then, for the purpose of resolving some of these issues, recent design and modeling efforts towards developing an improved neutron detection system are described. Also presented is a low-noise active pixel sensor (APS) design capable of being implemented in low temperature indium gallium zinc oxide (InGaZnO) or amorphous silicon (a-Si:H) thin film transistor process compatible with plastic substrates. The low gain and limited scalability of this design are improved upon by implementing a new multi-stage self-resetting APS. For each APS design, successful radiation measurements are also presented using PiN diodes for charged particle detection. Next, detection array readout methodologies are modeled and analyzed, and use of a matched filter readout circuit is described as well. Finally, this document discusses detection diode integration with the designed TFT-based APSs.

  9. 50 μm pixel pitch wafer-scale CMOS active pixel sensor x-ray detector for digital breast tomosynthesis.

    PubMed

    Zhao, C; Konstantinidis, A C; Zheng, Y; Anaxagoras, T; Speller, R D; Kanicki, J

    2015-12-07

    Wafer-scale CMOS active pixel sensors (APSs) have been developed recently for x-ray imaging applications. The small pixel pitch and low noise are very promising properties for medical imaging applications such as digital breast tomosynthesis (DBT). In this work, we evaluated experimentally and through modeling the imaging properties of a 50 μm pixel pitch CMOS APS x-ray detector named DynAMITe (Dynamic Range Adjustable for Medical Imaging Technology). A modified cascaded system model was developed for CMOS APS x-ray detectors by taking into account the device nonlinear signal and noise properties. The imaging properties such as modulation transfer function (MTF), noise power spectrum (NPS), and detective quantum efficiency (DQE) were extracted from both measurements and the nonlinear cascaded system analysis. The results show that the DynAMITe x-ray detector achieves a high spatial resolution of 10 mm(-1) and a DQE of around 0.5 at spatial frequencies  <1 mm(-1). In addition, the modeling results were used to calculate the image signal-to-noise ratio (SNRi) of microcalcifications at various mean glandular dose (MGD). For an average breast (5 cm thickness, 50% glandular fraction), 165 μm microcalcifications can be distinguished at a MGD of 27% lower than the clinical value (~1.3 mGy). To detect 100 μm microcalcifications, further optimizations of the CMOS APS x-ray detector, image aquisition geometry and image reconstruction techniques should be considered.

  10. Method of fabrication of display pixels driven by silicon thin film transistors

    DOEpatents

    Carey, Paul G.; Smith, Patrick M.

    1999-01-01

    Display pixels driven by silicon thin film transistors are fabricated on plastic substrates for use in active matrix displays, such as flat panel displays. The process for forming the pixels involves a prior method for forming individual silicon thin film transistors on low-temperature plastic substrates. Low-temperature substrates are generally considered as being incapable of withstanding sustained processing temperatures greater than about 200.degree. C. The pixel formation process results in a complete pixel and active matrix pixel array. A pixel (or picture element) in an active matrix display consists of a silicon thin film transistor (TFT) and a large electrode, which may control a liquid crystal light valve, an emissive material (such as a light emitting diode or LED), or some other light emitting or attenuating material. The pixels can be connected in arrays wherein rows of pixels contain common gate electrodes and columns of pixels contain common drain electrodes. The source electrode of each pixel TFT is connected to its pixel electrode, and is electrically isolated from every other circuit element in the pixel array.

  11. Silicon-on-insulator (SOI) active pixel sensors with the photosite implemented in the substrate

    NASA Technical Reports Server (NTRS)

    Pain, Bedabrata (Inventor); Zheng, Xinyu (Inventor)

    2002-01-01

    Active pixel sensors for a high quality imager are fabricated using a silicon-on-insulator (SOI) process by integrating the photodetectors on the SOI substrate and forming pixel readout transistors on the SOI thin-film. The technique can include forming silicon islands on a buried insulator layer disposed on a silicon substrate and selectively etching away the buried insulator layer over a region of the substrate to define a photodetector area. Dopants of a first conductivity type are implanted to form a signal node in the photodetector area and to form simultaneously drain/source regions for a first transistor in at least a first one of the silicon islands. Dopants of a second conductivity type are implanted to form drain/source regions for a second transistor in at least a second one of the silicon islands. Isolation rings around the photodetector also can be formed when dopants of the second conductivity type are implanted. Interconnections among the transistors and the photodetector are provided to allow signals sensed by the photodetector to be read out via the transistors formed on the silicon islands.

  12. Silicon-on-insulator (SOI) active pixel sensors with the photosite implemented in the substrate

    NASA Technical Reports Server (NTRS)

    Zheng, Xinyu (Inventor); Pain, Bedabrata (Inventor)

    2005-01-01

    Active pixel sensors for a high quality imager are fabricated using a silicon-on-insulator (SOI) process by integrating the photodetectors on the SOI substrate and forming pixel readout transistors on the SOI thin-film. The technique can include forming silicon islands on a buried insulator layer disposed on a silicon substrate and selectively etching away the buried insulator layer over a region of the substrate to define a photodetector area. Dopants of a first conductivity type are implanted to form a signal node in the photodetector area and to form simultaneously drain/source regions for a first transistor in at least a first one of the silicon islands. Dopants of a second conductivity type are implanted to form drain/source regions for a second transistor in at least a second one of the silicon islands. Isolation rings around the photodetector also can be formed when dopants of the second conductivity type are implanted. Interconnections among the transistors and the photodetector are provided to allow signals sensed by the photodetector to be read out via the transistors formed on the silicon islands.

  13. Direct tests of a pixelated microchannel plate as the active element of a shower maximum detector

    DOE PAGES

    Apresyan, A.; Los, S.; Pena, C.; ...

    2016-05-07

    One possibility to make a fast and radiation resistant shower maximum detector is to use a secondary emitter as an active element. We report our studies of microchannel plate photomultipliers (MCPs) as the active element of a shower-maximum detector. We present test beam results obtained using Photonis XP85011 to detect secondary particles of an electromagnetic shower. We focus on the use of the multiple pixels on the Photonis MCP in order to find a transverse two-dimensional shower distribution. A spatial resolution of 0.8 mm was obtained with an 8 GeV electron beam. As a result, a method for measuring themore » arrival time resolution for electromagnetic showers is presented, and we show that time resolution better than 40 ps can be achieved.« less

  14. Direct tests of a pixelated microchannel plate as the active element of a shower maximum detector

    SciTech Connect

    Apresyan, A.; Los, S.; Pena, C.; Presutti, F.; Ronzhin, A.; Spiropulu, M.; Xie, S.

    2016-05-07

    One possibility to make a fast and radiation resistant shower maximum detector is to use a secondary emitter as an active element. We report our studies of microchannel plate photomultipliers (MCPs) as the active element of a shower-maximum detector. We present test beam results obtained using Photonis XP85011 to detect secondary particles of an electromagnetic shower. We focus on the use of the multiple pixels on the Photonis MCP in order to find a transverse two-dimensional shower distribution. A spatial resolution of 0.8 mm was obtained with an 8 GeV electron beam. As a result, a method for measuring the arrival time resolution for electromagnetic showers is presented, and we show that time resolution better than 40 ps can be achieved.

  15. Relative dosimetry using active matrix flat-panel imager (AMFPI) technology.

    PubMed

    El-Mohri, Y; Antonuk, L E; Yorkston, J; Jee, K W; Maolinbay, M; Lam, K L; Siewerdsen, J H

    1999-08-01

    The first examination of the use of active matrix flat-panel arrays for dosimetry in radiotherapy is reported. Such arrays are under widespread development for diagnostic and radiotherapy imaging. In the current study, an array consisting of 512 x 512 pixels with a pixel pitch of 508 microm giving an area of 26 x 26 cm2 has been used. Each pixel consists of a light sensitive amorphous silicon (a-Si:H) photodiode coupled to an a-Si:H thin-film transistor. Data was obtained from the array using a dedicated electronics system allowing real-time data acquisition. In order to examine the potential of such arrays as quality assurance devices for radiotherapy beams, field profile data at photon energies of 6 and 15 MV were obtained as a function of field size and thickness of overlying absorbing material (solid water). Two detection configurations using the array were considered: a configuration (similar to the imaging configuration) in which an overlying phosphor screen is used to convert incident radiation to visible light photons which are detected by the photodiodes; and a configuration without the screen where radiation is directly sensed by the photodiodes. Compared to relative dosimetry data obtained with an ion chamber, data taken using the former configuration exhibited significant differences whereas data obtained using the latter configuration was generally found to be in close agreement. Basic signal properties, which are pertinent to dosimetry, have been investigated through measurements of individual pixel response for fluoroscopic and radiographic array operation. For signal levels acquired within the first 25% of pixel charge capacity, the degree of linear response with dose was found to be better than 99%. The independence of signal on dose rate was demonstrated by means of stability of pixel response over the range of dose rates allowed by the radiation source (80-400 MU/min). Finally, excellent long-term stability in pixel response, extending over a 2

  16. A radiation-hardened two transistor memory cell for monolithic active pixel sensors in STAR experiment

    NASA Astrophysics Data System (ADS)

    Wei, X.; Gao, D.; Dorokhov, A.; Hu, Y.

    2011-01-01

    Radiation tolerance of Monolithic Active Pixel Sensors (MAPS) is dramatically decreased when intellectual property (IP) memories are integrated for fast readout application. This paper presents a new solution to improve radiation hardness and avoid latch-up for memory cell design. The tradeoffs among radiation tolerance, area and speed are significantly considered and analyzed. The cell designed in 0.35 μm process satisfies the radiation tolerance requirements of STAR experiment. The cell size is 4.55 × 5.45 μm2. This cell is smaller than the IP memory cell based on the same process and is only 26% of a radiation tolerant 6T SRAM cell used in previous contribution. The write access time of the cell is less than 2 ns, while the read access time is 80 ns.

  17. Impact of Substrate Bias on Fixed-Pattern-Noise in Active Pixel Sensor Cells

    NASA Astrophysics Data System (ADS)

    Terauchi, Mamoru

    2007-11-01

    The effect of substrate (body) bias on fixed-pattern-noise (FPN) in active pixel sensor (APS) cells is studied. Through measuring test devices consisting of two metal-oxide-semiconductor field-effect transistors (MOSFETs) connected in series with each of the transistors located in the same well region, it has been revealed that substrate bias, which is inevitably applied in a normal circuit configuration in conventional APS cells, worsens the characteristics fluctuation in source-follower amplifiers in APS cells, leading to FPN that cannot be mitigated by conventional correction methods such as correlated double sampling. In addition it has been confirmed that the current-voltage characteristics of logarithmic converters, each of which is realized using a MOSFET with gate and drain terminals connected together, are also affected by substrate bias, resulting in increased characteristics fluctuation as compared with the case with no substrate bias.

  18. A Monolithic Active Pixel Sensor for ionizing radiation using a 180 nm HV-SOI process

    NASA Astrophysics Data System (ADS)

    Hemperek, Tomasz; Kishishita, Tetsuichi; Krüger, Hans; Wermes, Norbert

    2015-10-01

    An improved SOI-MAPS (Silicon On Insulator Monolithic Active Pixel Sensor) for ionizing radiation based on thick-film High Voltage SOI technology (HV-SOI) has been developed. Similar to existing Fully Depleted SOI-based (FD-SOI) MAPS, a buried silicon oxide inter-dielectric (BOX) layer is used to separate the CMOS electronics from the handle wafer which is used as a depleted charge collection layer. FD-SOI MAPS suffers from radiation damage such as transistor threshold voltage shifts due to charge traps in the oxide layers and charge states created at the silicon oxide boundaries (back gate effect). The X-FAB 180-nm HV-SOI technology offers an additional isolation by deep non-depleted implant between the BOX layer and the active circuitry which mitigates this problem. Therefore we see in this technology a high potential to implement radiation-tolerant MAPS with fast charge collection property. The design and measurement results from a first prototype are presented including charge collection in neutron irradiated samples.

  19. Integrated X-ray and charged particle active pixel CMOS sensor arrays using an epitaxial silicon sensitive region

    SciTech Connect

    Kleinfelder, Stuart; Bichsel, Hans; Bieser, Fred; Matis, Howard S.; Rai, Gulshan; Retiere, Fabrice; Weiman, Howard; Yamamoto, Eugene

    2002-07-01

    Integrated CMOS Active Pixel Sensor (APS) arrays have been fabricated and tested using X-ray and electron sources. The 128 by 128 pixel arrays, designed in a standard 0.25 micron process, use a {approx}10 micron epitaxial silicon layer as a deep detection region. The epitaxial layer has a much greater thickness than the surface features used by standard CMOS APS, leading to stronger signals and potentially better signal-to-noise ratio (SNR). On the other hand, minority carriers confined within the epitaxial region may diffuse to neighboring pixels, blur images and reduce peak signal intensity. But for low-rate, sparse-event images, centroid analysis of this diffusion may be used to increase position resolution. Careful trade-offs involving pixel size and sense-node area verses capacitance must be made to optimize overall performance. The prototype sensor arrays, therefore, include a range of different pixel designs, including different APS circuits and a range of different epitaxial layer contact structures. The fabricated arrays were tested with 1.5 GeV electrons and Fe-55 X-ray sources, yielding a measured noise of 13 electrons RMS and an SNR for single Fe-55 X-rays of greater than 38.

  20. Proof of principle study of the use of a CMOS active pixel sensor for proton radiography

    SciTech Connect

    Seco, Joao; Depauw, Nicolas

    2011-02-15

    Purpose: Proof of principle study of the use of a CMOS active pixel sensor (APS) in producing proton radiographic images using the proton beam at the Massachusetts General Hospital (MGH). Methods: A CMOS APS, previously tested for use in s-ray radiation therapy applications, was used for proton beam radiographic imaging at the MGH. Two different setups were used as a proof of principle that CMOS can be used as proton imaging device: (i) a pen with two metal screws to assess spatial resolution of the CMOS and (ii) a phantom with lung tissue, bone tissue, and water to assess tissue contrast of the CMOS. The sensor was then traversed by a double scattered monoenergetic proton beam at 117 MeV, and the energy deposition inside the detector was recorded to assess its energy response. Conventional x-ray images with similar setup at voltages of 70 kVp and proton images using commercial Gafchromic EBT 2 and Kodak X-Omat V films were also taken for comparison purposes. Results: Images were successfully acquired and compared to x-ray kVp and proton EBT2/X-Omat film images. The spatial resolution of the CMOS detector image is subjectively comparable to the EBT2 and Kodak X-Omat V film images obtained at the same object-detector distance. X-rays have apparent higher spatial resolution than the CMOS. However, further studies with different commercial films using proton beam irradiation demonstrate that the distance of the detector to the object is important to the amount of proton scatter contributing to the proton image. Proton images obtained with films at different distances from the source indicate that proton scatter significantly affects the CMOS image quality. Conclusion: Proton radiographic images were successfully acquired at MGH using a CMOS active pixel sensor detector. The CMOS demonstrated spatial resolution subjectively comparable to films at the same object-detector distance. Further work will be done in order to establish the spatial and energy resolution of the

  1. Active pixel image sensor with a winner-take-all mode of operation

    NASA Technical Reports Server (NTRS)

    Yadid-Pecht, Orly (Inventor); Fossum, Eric R. (Inventor); Mead, Carver (Inventor)

    2003-01-01

    An integrated CMOS semiconductor imaging device having two modes of operation that can be performed simultaneously to produce an output image and provide information of a brightest or darkest pixel in the image.

  2. Characterization of high resolution CMOS monolithic active pixel detector in SOI technology

    NASA Astrophysics Data System (ADS)

    Ahmed, M. I.; Arai, Y.; Glab, S.; Idzik, M.; Kapusta, P.; Miyoshi, T.; Takeda, A.; Turala, M.

    2015-05-01

    Novel CMOS monolithic pixel detectors designed at KEK and fabricated at Lapis Semiconductor in 0.2 μm Silicon-on-Insulator (SOI) technology are presented. A thin layer of silicon oxide separates high and low resistivity silicon layers, allowing for optimization of design of detector and readout parts. Shallow wells buried under the oxide in the detector part screen the entire pixel electronics from electrical field applied to the detector. Several integration type SOI pixel detectors have been developed with pixel sizes 8-20 μm. The general features of 14 × 14 μm2 detectors designed on different wafers (CZ-n, FZ-n and FZ-p) were measured and compared. The detector performance was studied under irradiation with visible and infra-red laser, and also X-ray ionizing source. Using X-rays from an Am-241 source the noise of readout electronics was measured at different working conditions, showing the ENC in the range of 88-120 e-. The pixel current was calculated from average DC pedestal shift while varying the pixel integration time. The operation of the detector was studied under partial and full depletion conditions. The effects of temperature and detector bias voltage on noise and leakage current were studied. Characteristics of an ADC integrated in the front-end chip are also presented.

  3. A novel source-drain follower for monolithic active pixel sensors

    NASA Astrophysics Data System (ADS)

    Gao, C.; Aglieri, G.; Hillemanns, H.; Huang, G.; Junique, A.; Keil, M.; Kim, D.; Kofarago, M.; Kugathasan, T.; Mager, M.; Marin Tobon, C. A.; Martinengo, P.; Mugnier, H.; Musa, L.; Lee, S.; Reidt, F.; Riedler, P.; Rousset, J.; Sielewicz, K. M.; Snoeys, W.; Sun, X.; Van Hoorne, J. W.; Yang, P.

    2016-09-01

    Monolithic active pixel sensors (MAPS) receive interest in tracking applications in high energy physics as they integrate sensor and readout electronics in one silicon die with potential for lower material budget and cost, and better performance. Source followers (SFs) are widely used for MAPS readout: they increase charge conversion gain 1/Ceff or decrease the effective sensing node capacitance Ceff because the follower action compensates part of the input capacitance. Charge conversion gain is critical for analog power consumption and therefore for material budget in tracking applications, and also has direct system impact. This paper presents a novel source-drain follower (SDF), where both source and drain follow the gate potential improving charge conversion gain. For the inner tracking system (ITS) upgrade of the ALICE experiment at CERN, low material budget is a primary requirement. The SDF circuit was studied as part of the effort to optimize the effective capacitance of the sensing node. The collection electrode, input transistor and routing metal all contribute to Ceff. Reverse sensor bias reduces the collection electrode capacitance. The novel SDF circuit eliminates the contribution of the input transistor to Ceff, reduces the routing contribution if additional shielding is introduced, provides a way to estimate the capacitance of the sensor itself, and has a voltage gain closer to unity than the standard SF. The SDF circuit has a somewhat larger area with a somewhat smaller bandwidth, but this is acceptable in most cases. A test chip, manufactured in a 180 nm CMOS image sensor process, implements small prototype pixel matrices in different flavors to compare the standard SF to the novel SF and to the novel SF with additional shielding. The effective sensing node capacitance was measured using a 55Fe source. Increasing reverse substrate bias from -1 V to -6 V reduces Ceff by 38% and the equivalent noise charge (ENC) by 22% for the standard SF. The SDF

  4. Compact VLSI neural computer integrated with active pixel sensor for real-time ATR applications

    NASA Astrophysics Data System (ADS)

    Fang, Wai-Chi; Udomkesmalee, Gabriel; Alkalai, Leon

    1997-04-01

    A compact VLSI neural computer integrated with an active pixel sensor has been under development to mimic what is inherent in biological vision systems. This electronic eye- brain computer is targeted for real-time machine vision applications which require both high-bandwidth communication and high-performance computing for data sensing, synergy of multiple types of sensory information, feature extraction, target detection, target recognition, and control functions. The neural computer is based on a composite structure which combines Annealing Cellular Neural Network (ACNN) and Hierarchical Self-Organization Neural Network (HSONN). The ACNN architecture is a programmable and scalable multi- dimensional array of annealing neurons which are locally connected with their local neurons. Meanwhile, the HSONN adopts a hierarchical structure with nonlinear basis functions. The ACNN+HSONN neural computer is effectively designed to perform programmable functions for machine vision processing in all levels with its embedded host processor. It provides a two order-of-magnitude increase in computation power over the state-of-the-art microcomputer and DSP microelectronics. A compact current-mode VLSI design feasibility of the ACNN+HSONN neural computer is demonstrated by a 3D 16X8X9-cube neural processor chip design in a 2-micrometers CMOS technology. Integration of this neural computer as one slice of a 4'X4' multichip module into the 3D MCM based avionics architecture for NASA's New Millennium Program is also described.

  5. 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.

  6. Simulation of active-edge pixelated CdTe radiation detectors

    NASA Astrophysics Data System (ADS)

    Duarte, D. D.; Lipp, J. D.; Schneider, A.; Seller, P.; Veale, M. C.; Wilson, M. D.; Baker, M. A.; Sellin, P. J.

    2016-01-01

    The edge surfaces of single crystal CdTe play an important role in the electronic properties and performance of this material as an X-ray and γ-ray radiation detector. Edge effects have previously been reported to reduce the spectroscopic performance of the edge pixels in pixelated CdTe radiation detectors without guard bands. A novel Technology Computer Aided Design (TCAD) model based on experimental data has been developed to investigate these effects. The results presented in this paper show how localized low resistivity surfaces modify the internal electric field of CdTe creating potential wells. These result in a reduction of charge collection efficiency of the edge pixels, which compares well with experimental data.

  7. Thin n-in-p planar pixel sensors and active edge sensors for the ATLAS upgrade at HL-LHC

    NASA Astrophysics Data System (ADS)

    Terzo, S.; Macchiolo, A.; Nisius, R.; Paschen, B.

    2014-12-01

    Silicon pixel modules employing n-in-p planar sensors with an active thickness of 200 μm, produced at CiS, and 100-200 μm thin active/slim edge sensor devices, produced at VTT in Finland have been interconnected to ATLAS FE-I3 and FE-I4 read-out chips. The thin sensors are designed for high energy physics collider experiments to ensure radiation hardness at high fluences. Moreover, the active edge technology of the VTT production maximizes the sensitive region of the assembly, allowing for a reduced overlap of the modules in the pixel layer close to the beam pipe. The CiS production includes also four chip sensors according to the module geometry planned for the outer layers of the upgraded ATLAS pixel detector to be operated at the HL-LHC. The modules have been characterized using radioactive sources in the laboratory and with high precision measurements at beam tests to investigate the hit efficiency and charge collection properties at different bias voltages and particle incidence angles. The performance of the different sensor thicknesses and edge designs are compared before and after irradiation up to a fluence of 1.4 × 1016 neq/cm2.

  8. PIXEL PUSHER

    NASA Technical Reports Server (NTRS)

    Stanfill, D. F.

    1994-01-01

    Pixel Pusher is a Macintosh application used for viewing and performing minor enhancements on imagery. It will read image files in JPL's two primary image formats- VICAR and PDS - as well as the Macintosh PICT format. VICAR (NPO-18076) handles an array of image processing capabilities which may be used for a variety of applications including biomedical image processing, cartography, earth resources, and geological exploration. Pixel Pusher can also import VICAR format color lookup tables for viewing images in pseudocolor (256 colors). This program currently supports only eight bit images but will work on monitors with any number of colors. Arbitrarily large image files may be viewed in a normal Macintosh window. Color and contrast enhancement can be performed with a graphical "stretch" editor (as in contrast stretch). In addition, VICAR images may be saved as Macintosh PICT files for exporting into other Macintosh programs, and individual pixels can be queried to determine their locations and actual data values. Pixel Pusher is written in Symantec's Think C and was developed for use on a Macintosh SE30, LC, or II series computer running System Software 6.0.3 or later and 32 bit QuickDraw. Pixel Pusher will only run on a Macintosh which supports color (whether a color monitor is being used or not). The standard distribution medium for this program is a set of three 3.5 inch Macintosh format diskettes. The program price includes documentation. Pixel Pusher was developed in 1991 and is a copyrighted work with all copyright vested in NASA. Think C is a trademark of Symantec Corporation. Macintosh is a registered trademark of Apple Computer, Inc.

  9. Characterization of CMOS Active Pixel Sensors for particle detection: Beam test of the four-sensors RAPS03 stacked system

    NASA Astrophysics Data System (ADS)

    Passeri, Daniele; Servoli, Leonello; Biagetti, Daniele; Meroli, Stefano

    2010-05-01

    In this work, in order to check the suitability of CMOS Active Pixel Sensors (APS) detectors for vertexing/tracking applications, four stacked CMOS APS sensors featuring 256×256 pixels with 10×10 μm 2 size have been tested at the INFN Beam Test Facility (BFT), Frascati (Rome). For this purpose, a dedicated mechanical and electrical set-up has been devised and implemented, allowing for the simultaneous read-out of four sensors arranged in a stacked structure. A compact and fast system (up to 64 MHz read-out clock) based on external ADCs and FPGA allows for the PC communication through USB2.0. Preliminary results in terms of track reconstructions of electrons of different energies (up to 496 MeV) are presented. This work has been carried out within the framework of the SHARPS project, supported by INFN.

  10. Pixel Perfect

    SciTech Connect

    Perrine, Kenneth A.; Hopkins, Derek F.; Lamarche, Brian L.; Sowa, Marianne B.

    2005-09-01

    Biologists and computer engineers at Pacific Northwest National Laboratory have specified, designed, and implemented a hardware/software system for performing real-time, multispectral image processing on a confocal microscope. This solution is intended to extend the capabilities of the microscope, enabling scientists to conduct advanced experiments on cell signaling and other kinds of protein interactions. FRET (fluorescence resonance energy transfer) techniques are used to locate and monitor protein activity. In FRET, it is critical that spectral images be precisely aligned with each other despite disturbances in the physical imaging path caused by imperfections in lenses and cameras, and expansion and contraction of materials due to temperature changes. The central importance of this work is therefore automatic image registration. This runs in a framework that guarantees real-time performance (processing pairs of 1024x1024, 8-bit images at 15 frames per second) and enables the addition of other types of advanced image processing algorithms such as image feature characterization. The supporting system architecture consists of a Visual Basic front-end containing a series of on-screen interfaces for controlling various aspects of the microscope and a script engine for automation. One of the controls is an ActiveX component written in C++ for handling the control and transfer of images. This component interfaces with a pair of LVDS image capture boards and a PCI board containing a 6-million gate Xilinx Virtex-II FPGA. Several types of image processing are performed on the FPGA in a pipelined fashion, including the image registration. The FPGA offloads work that would otherwise need to be performed by the main CPU and has a guaranteed real-time throughput. Image registration is performed in the FPGA by applying a cubic warp on one image to precisely align it with the other image. Before each experiment, an automated calibration procedure is run in order to set up the

  11. Imaging of moving fiducial markers during radiotherapy using a fast, efficient active pixel sensor based EPID

    SciTech Connect

    Osmond, John P. F.; Zin, Hafiz M.; Harris, Emma J.; Lupica, Giovanni; Allinson, Nigel M.; Evans, Philip M.

    2011-11-15

    Purpose: The purpose of this work was to investigate the use of an experimental complementary metal-oxide-semiconductor (CMOS) active pixel sensor (APS) for tracking of moving fiducial markers during radiotherapy. Methods: The APS has an active area of 5.4 x 5.4 cm and maximum full frame read-out rate of 20 frame s{sup -1}, with the option to read out a region-of-interest (ROI) at an increased rate. It was coupled to a 4 mm thick ZnWO4 scintillator which provided a quantum efficiency (QE) of 8% for a 6 MV x-ray treatment beam. The APS was compared with a standard iViewGT flat panel amorphous Silicon (a-Si) electronic portal imaging device (EPID), with a QE of 0.34% and a frame-rate of 2.5 frame s{sup -1}. To investigate the ability of the two systems to image markers, four gold cylinders of length 8 mm and diameter 0.8, 1.2, 1.6, and 2 mm were placed on a motion-platform. Images of the stationary markers were acquired using the APS at a frame-rate of 20 frame s{sup -1}, and a dose-rate of 143 MU min{sup -1} to avoid saturation. EPID images were acquired at the maximum frame-rate of 2.5 frame s{sup -1}, and a reduced dose-rate of 19 MU min{sup -1} to provide a similar dose per frame to the APS. Signal-to-noise ratio (SNR) of the background signal and contrast-to-noise ratio (CNR) of the marker signal relative to the background were evaluated for both imagers at doses of 0.125 to 2 MU. Results: Image quality and marker visibility was found to be greater in the APS with SNR {approx}5 times greater than in the EPID and CNR up to an order of magnitude greater for all four markers. To investigate the ability to image and track moving markers the motion-platform was moved to simulate a breathing cycle with period 6 s, amplitude 20 mm and maximum speed 13.2 mm s{sup -1}. At the minimum integration time of 50 ms a tracking algorithm applied to the APS data found all four markers with a success rate of {>=}92% and positional error {<=}90 {mu}m. At an integration time of 400

  12. High-dynamic-range pixel architectures for diagnostic medical imaging

    NASA Astrophysics Data System (ADS)

    Karim, Karim S.; Yin, Sherman; Nathan, Arokia; Rowlands, John A.

    2004-05-01

    One approach to increase pixel signal-to-noise ratio (SNR) in low noise digital fluoroscopy is to employ in-situ pixel amplification via current-mediated active pixel sensors (C-APS). Experiments reveal a reduction in readout noise and indicate that an a-Si C-APS, coupled together with an established X-ray detection technology such as amorphous selenium (a-Se), can meet the stringent requirements (of < 1000 noise electrons) for digital X-ray fluoroscopy. A challenge with the C-APS circuit is the presence of a small-signal input linearity constraint. While using such a pixel amplifier for real-time fluoroscopy (where the exposure level is small) is feasible, the voltage change at the amplifier input is much higher in chest radiography or mammography due to the larger X-ray exposure levels. The larger input voltage causes the C-APS output to be non-linear thus reducing the pixel dynamic range. In addition, the resulting larger pixel output current causes the external column amplifier to saturate further reducing the pixel dynamic range. In this research, we investigate two alternate amplified pixel architectures that exhibit higher dynamic range. The test pixels are designed and simulated using an a-Si TFT model implemented in Verilog-A and results indicate a linear performance, high dynamic range, and a programmable circuit gain via choice of supply voltage and sampling time. These high dynamic range pixel architectures have the potential to enable a large area, active matrix flat panel imager (AMFPI) to switch instantly between low exposure, fluoroscopic imaging and higher exposure radiographic imaging modes. Lastly, the high dynamic range pixel circuits are suitable for integration with on-panel multiplexers for both gate and data lines, which can further reduce circuit complexity.

  13. Equivalence of a Bit Pixel Image to a Quantum Pixel Image

    NASA Astrophysics Data System (ADS)

    Ortega, Laurel Carlos; Dong, Shi-Hai; Cruz-Irisson, M.

    2015-11-01

    We propose a new method to transform a pixel image to the corresponding quantum-pixel using a qubit per pixel to represent each pixels classical weight in a quantum image matrix weight. All qubits are linear superposition, changing the coefficients level by level to the entire longitude of the gray scale with respect to the base states of the qubit. Classically, these states are just bytes represented in a binary matrix, having code combinations of 1 or 0 at all pixel locations. This method introduces a qubit-pixel image representation of images captured by classical optoelectronic methods. Supported partially by the project 20150964-SIP-IPN, Mexico

  14. Spectroscopic performance of DEPFET active pixel sensor prototypes suitable for the high count rate Athena WFI detector

    NASA Astrophysics Data System (ADS)

    Müller-Seidlitz, Johannes; Andritschke, Robert; Bähr, Alexander; Meidinger, Norbert; Ott, Sabine; Richter, Rainer H.; Treberspurg, Wolfgang; Treis, Johannes

    2016-07-01

    The focal plane of the WFI of Athena consists of two sensors. One features a large field of view of 40' X 40' and one is forseen to be used for bright point like sources. Both parts base on DEPFET active pixel sensors. To fulfil the count rate requirement for the smaller sensor of less than 1% pile-up for a one Crab source it has to have a sufficient high frame rate. Since therefore the readout becomes a large fraction of the total photon integration time, the probability of measurements with incomplete signals increases. A shutter would solve the problem of these so called misfits but is not in agreement with the required high throughput of more than 80%. The Infinipix design has implemented a storage in addition to separate the collection and the readout of the charges without discarding them. Its working principle was successfully shown by Bähr et al.1 on single pixel level. For the further development three layout variants were tested on a 32 X 32 pixel array scale. The measurements of the spectroscopic performance show very promising results even for the intended readout speed for the Athena WFI of 2:5 μs per sensor row. Although, there are still layout and technology improvements necessary to ensure the reliability needed for space missions. In this paper we present the measurement results on the comparison of the three prototype layout variants.

  15. Active pixel sensors in AMS H18/H35 HV-CMOS technology for the ATLAS HL-LHC upgrade

    NASA Astrophysics Data System (ADS)

    Ristic, Branislav

    2016-09-01

    Deep sub micron HV-CMOS processes offer the opportunity for sensors built by industry standard techniques while being HV tolerant, making them good candidates for drift-based, fast collecting, thus radiation-hard pixel detectors. For the upgrade of the ATLAS Pixel Detector towards the HL-LHC requirements, active pixel sensors in HV-CMOS technology were investigated. These implement signal processing electronics in deep n-wells, which also act as collecting electrodes. The deep n-wells allow for bias voltages up to 150 V leading to a depletion depth of several 10 μm. Prototype sensors in the AMS H18 180 nm and H35 350 nm HV-CMOS processes were thoroughly tested in lab measurements as well as in testbeam experiments. Irradiations with X-rays and protons revealed a tolerance to ionizing doses of 1 Grad while Edge-TCT studies assessed the effects of radiation on the charge collection. The sensors showed high detection efficiencies after neutron irradiation to 1015neq cm-2 in testbeam experiments. A full reticle size demonstrator chip, implemented in the H35 process is being submitted to prove the large scale feasibility of the HV-CMOS concept.

  16. High-End CMOS Active Pixel Sensors For Space-Borne Imaging Instruments

    DTIC Science & Technology

    2005-07-13

    sur la technologie CCD, alors que les capteurs CMOS à pixel actifs (APS) ont des nombreux avantages pour des applications embarquées. Cette...Les capteurs optiques intégrés sont utilisés dans le domaine spatial dans un large éventail d’applications. Beaucoup d’entres elles reposent toujours...publication présente des capteurs CMOS hautes performances d’aujourd’hui et met en lumière leurs avantages par rapport à leur équivalent CCD. Ces capteurs

  17. Signal and noise transfer properties of CMOS based active pixel flat panel imager coupled to structured CsI:Tl.

    PubMed

    Arvanitis, C D; Bohndiek, S E; Blakesley, J; Olivo, A; Speller, R D

    2009-01-01

    Complementary metal-oxide-semiconductors (CMOS) active pixel sensors can be optically coupled to CsI:Tl phosphors forming a indirect active pixel flat panel imager (APFPI) for high performance medical imaging. The aim of this work is to determine the x-ray imaging capabilities of CMOS-based APFPI and study the signal and noise transfer properties of CsI:Tl phosphors. Three different CsI:Tl phosphors from two different vendors have been used to produce three system configurations. The performance of each system configuration has been studied in terms of the modulation transfer function (MTF), noise power spectra, and detective quantum efficiency (DQE) in the mammographic energy range. A simple method to determine quantum limited systems in this energy range is also presented. In addition, with aid of monochromatic synchrotron radiation, the effect of iodine characteristic x-rays of the CsI:Tl on the MTF has been determined. A Monte Carlo simulation of the signal transfer properties of the imager is also presented in order to study the stages that degrade the spatial resolution of our current system. The effect of using substrate patterning during the growth of CsI:Tl columnar structure was also studied, along with the effect of CsI:Tl fixed pattern noise due to local variations in the scintillation light. CsI:Tl fixed pattern noise appears to limit the performance of our current system configurations. All the system configurations are quantum limited at 0.23 microC/kg with two of them having DQE (0) equal to 0.57. Active pixel flat panel imagers are shown to be digital x-ray imagers with almost constant DQE throughout a significant part of their dynamic range and in particular at very low exposures.

  18. 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.

  19. 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.

  20. Membrane type-1 matrix metalloprotease-independent activation of pro-matrix metalloprotease-2 by proprotein convertases.

    PubMed

    Koo, Bon-Hun; Kim, Hee-Hyun; Park, Michael Y; Jeon, Ok-Hee; Kim, Doo-Sik

    2009-11-01

    Matrix metalloprotease-2 is implicated in many biological processes and degrades extracellular and non-extracellular matrix molecules. Matrix metalloprotease-2 maintains a latent state through a cysteine-zinc ion pairing which, when disrupted, results in full enzyme activation. This pairing can be disrupted by a conformational change or cleavage within the propeptide. The best known activation mechanism for pro-matrix metalloprotease-2 occurs via cleavage of the propeptide by membrane type-1 matrix metalloprotease. However, significant residual activation of pro-matrix metalloprotease-2 is seen in membrane type-1 matrix metalloprotease knockout mice and in fibroblasts treated with metalloprotease inhibitors. These findings indicate the presence of a membrane type-1 matrix metalloprotease-independent activation mechanism for pro-matrix metalloprotease-2 in vivo, which prompted us to explore an alternative activation mechanism for pro-matrix metalloprotese-2. In this study, we demonstrate membrane type-1 matrix metalloprotease-independent propeptide processing of matrix metalloprotease-2 in HEK293F and various tumor cell lines, and show that proprotein convertases can mediate the processing intracellularly as well as extracellularly. Furthermore, processed matrix metalloprotease-2 exhibits enzymatic activity that is enhanced by intermolecular autolytic cleavage. Thus, our experimental data, taken together with the broad expression of proprotein convertases, suggest that the proprotein convertase-mediated processing may be a general activation mechanism for pro-matrix metalloprotease-2 in vivo.

  1. Synchrotron based planar imaging and digital tomosynthesis of breast and biopsy phantoms using a CMOS active pixel sensor.

    PubMed

    Szafraniec, Magdalena B; Konstantinidis, Anastasios C; Tromba, Giuliana; Dreossi, Diego; Vecchio, Sara; Rigon, Luigi; Sodini, Nicola; Naday, Steve; Gunn, Spencer; McArthur, Alan; Olivo, Alessandro

    2015-03-01

    The SYRMEP (SYnchrotron Radiation for MEdical Physics) beamline at Elettra is performing the first mammography study on human patients using free-space propagation phase contrast imaging. The stricter spatial resolution requirements of this method currently force the use of conventional films or specialized computed radiography (CR) systems. This also prevents the implementation of three-dimensional (3D) approaches. This paper explores the use of an X-ray detector based on complementary metal-oxide-semiconductor (CMOS) active pixel sensor (APS) technology as a possible alternative, for acquisitions both in planar and tomosynthesis geometry. Results indicate higher quality of the images acquired with the synchrotron set-up in both geometries. This improvement can be partly ascribed to the use of parallel, collimated and monochromatic synchrotron radiation (resulting in scatter rejection, no penumbra-induced blurring and optimized X-ray energy), and partly to phase contrast effects. Even though the pixel size of the used detector is still too large - and thus suboptimal - for free-space propagation phase contrast imaging, a degree of phase-induced edge enhancement can clearly be observed in the images.

  2. a Portable Pixel Detector Operating as AN Active Nuclear Emulsion and its Application for X-Ray and Neutron Tomography

    NASA Astrophysics Data System (ADS)

    Vykydal, Z.; Jakubek, J.; Holy, T.; Pospisil, S.

    2006-04-01

    This work is devoted to the development of a USB1.1 (Universal Serial Bus) based read out system for the Medipix2 detector to achieve maximum portability of this position sensitive detecting device. All necessary detector support is integrated into one compact system (80 × 50 × 20 mm3) including the detector bias source (up to 100 V). The read out interface can control external I2C based devices, so in case of tomography it is easy to synchronize detector shutter with stepper motor control. An additional significant advantage of the USB interface is the support of back side pulse processing. This feature enables to determine the energy additionally to the position of a heavy charged particle hitting the sensor. Due to the small pixel dimensions it is also possible to distinguish the type of single quanta of radiation from the track created in the pixel detector as in case of an active nuclear emulsion.

  3. Active Matrix Driving Organic Light-Emitting Diode Panel Using Organic Thin-Film Transistors

    NASA Astrophysics Data System (ADS)

    Ohta, Satoru; Chuman, Takashi; Miyaguchi, Satoshi; Satoh, Hideo; Tanabe, Takahisa; Okuda, Yoshiyuki; Tsuchida, Masami

    2005-06-01

    We developed an active matrix driving organic light-emitting diode (OLED) panel on a glass substrate using two organic thin-film transistors (OTFTs) per pixel, a switching OTFT and a driving OTFT. The OTFTs are bottom contact structures with the high-dielectric constant gate insulator tantalum oxide (Ta2O5, relative dielectric constant of 23) produced by anodization in ammonium adipate solution and with pentacene as the active layer. The W/L (where W and L are the OTFTs channel width and length, respectively) was 400 μm/10 μm for the switching OTFTs and 680 μm/10 μm for the driving OTFTs. The characteristics of the OTFTs were improved by treating the Ta2O5 surface with hexamethyldisilazane (HMDS), so that the field-effect mobility was 2.0× 10-1 cm2 V-1 s-1 and the current on/off ratio was 105. A green phosphorescent dopant, tris(2-phenylpyridine)iridium [Ir(ppy)3], was used for the OLED layer. The panel had 8× 8 pixels and the aperture ratio was 27%. We confirmed a 16-gray-scale representation and a luminance of 400 cd/m2.

  4. 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.

  5. Imaging properties of pixellated scintillators with deep pixels

    PubMed Central

    Barber, H. Bradford; Fastje, David; Lemieux, Daniel; Grim, Gary P.; Furenlid, Lars R.; Miller, Brian W.; Parkhurst, Philip; Nagarkar, Vivek V.

    2015-01-01

    We have investigated the light-transport properties of scintillator arrays with long, thin pixels (deep pixels) for use in high-energy gamma-ray imaging. We compared 10×10 pixel arrays of YSO:Ce, LYSO:Ce and BGO (1mm × 1mm × 20 mm pixels) made by Proteus, Inc. with similar 10×10 arrays of LSO:Ce and BGO (1mm × 1mm × 15mm pixels) loaned to us by Saint-Gobain. The imaging and spectroscopic behaviors of these scintillator arrays are strongly affected by the choice of a reflector used as an inter-pixel spacer (3M ESR in the case of the Proteus arrays and white, diffuse-reflector for the Saint-Gobain arrays). We have constructed a 3700-pixel LYSO:Ce Prototype NIF Gamma-Ray Imager for use in diagnosing target compression in inertial confinement fusion. This system was tested at the OMEGA Laser and exhibited significant optical, inter-pixel cross-talk that was traced to the use of a single-layer of ESR film as an inter-pixel spacer. We show how the optical cross-talk can be mapped, and discuss correction procedures. We demonstrate a 10×10 YSO:Ce array as part of an iQID (formerly BazookaSPECT) imager and discuss issues related to the internal activity of 176Lu in LSO:Ce and LYSO:Ce detectors. PMID:26236070

  6. Imaging properties of pixellated scintillators with deep pixels

    NASA Astrophysics Data System (ADS)

    Barber, H. Bradford; Fastje, David; Lemieux, Daniel; Grim, Gary P.; Furenlid, Lars R.; Miller, Brian W.; Parkhurst, Philip; Nagarkar, Vivek V.

    2014-09-01

    We have investigated the light-transport properties of scintillator arrays with long, thin pixels (deep pixels) for use in high-energy gamma-ray imaging. We compared 10x10 pixel arrays of YSO:Ce, LYSO:Ce and BGO (1mm x 1mm x 20 mm pixels) made by Proteus, Inc. with similar 10x10 arrays of LSO:Ce and BGO (1mm x 1mm x 15mm pixels) loaned to us by Saint-Gobain. The imaging and spectroscopic behaviors of these scintillator arrays are strongly affected by the choice of a reflector used as an inter-pixel spacer (3M ESR in the case of the Proteus arrays and white, diffuse-reflector for the Saint-Gobain arrays). We have constructed a 3700-pixel LYSO:Ce Prototype NIF Gamma-Ray Imager for use in diagnosing target compression in inertial confinement fusion. This system was tested at the OMEGA Laser and exhibited significant optical, inter-pixel cross-talk that was traced to the use of a single-layer of ESR film as an inter-pixel spacer. We show how the optical cross-talk can be mapped, and discuss correction procedures. We demonstrate a 10x10 YSO:Ce array as part of an iQID (formerly BazookaSPECT) imager and discuss issues related to the internal activity of 176Lu in LSO:Ce and LYSO:Ce detectors.

  7. Imaging properties of pixellated scintillators with deep pixels.

    PubMed

    Barber, H Bradford; Fastje, David; Lemieux, Daniel; Grim, Gary P; Furenlid, Lars R; Miller, Brian W; Parkhurst, Philip; Nagarkar, Vivek V

    2014-08-17

    We have investigated the light-transport properties of scintillator arrays with long, thin pixels (deep pixels) for use in high-energy gamma-ray imaging. We compared 10×10 pixel arrays of YSO:Ce, LYSO:Ce and BGO (1mm × 1mm × 20 mm pixels) made by Proteus, Inc. with similar 10×10 arrays of LSO:Ce and BGO (1mm × 1mm × 15mm pixels) loaned to us by Saint-Gobain. The imaging and spectroscopic behaviors of these scintillator arrays are strongly affected by the choice of a reflector used as an inter-pixel spacer (3M ESR in the case of the Proteus arrays and white, diffuse-reflector for the Saint-Gobain arrays). We have constructed a 3700-pixel LYSO:Ce Prototype NIF Gamma-Ray Imager for use in diagnosing target compression in inertial confinement fusion. This system was tested at the OMEGA Laser and exhibited significant optical, inter-pixel cross-talk that was traced to the use of a single-layer of ESR film as an inter-pixel spacer. We show how the optical cross-talk can be mapped, and discuss correction procedures. We demonstrate a 10×10 YSO:Ce array as part of an iQID (formerly BazookaSPECT) imager and discuss issues related to the internal activity of (176)Lu in LSO:Ce and LYSO:Ce detectors.

  8. 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.

  9. Carbon nanotube active-matrix backplanes for conformal electronics and sensors.

    PubMed

    Takahashi, Toshitake; Takei, Kuniharu; Gillies, Andrew G; Fearing, Ronald S; Javey, Ali

    2011-12-14

    In this paper, we report a promising approach for fabricating large-scale flexible and stretchable electronics using a semiconductor-enriched carbon nanotube solution. Uniform semiconducting nanotube networks with superb electrical properties (mobility of ∼20 cm2 V(-1) s(-1) and ION/IOFF of ∼10(4)) are obtained on polyimide substrates. The substrate is made stretchable by laser cutting a honeycomb mesh structure, which combined with nanotube-network transistors enables highly robust conformal electronic devices with minimal device-to-device stochastic variations. The utility of this device concept is demonstrated by fabricating an active-matrix backplane (12×8 pixels, physical size of 6×4 cm2) for pressure mapping using a pressure sensitive rubber as the sensor element.

  10. Linear analysis of signal and noise characteristics of a nonlinear CMOS active-pixel detector for mammography

    NASA Astrophysics Data System (ADS)

    Yun, Seungman; Kim, Ho Kyung; Han, Jong Chul; Kam, Soohwa; Youn, Hanbean; Cunningham, Ian A.

    2017-03-01

    The imaging properties of a complementary metal-oxide-semiconductor (CMOS) active-pixel photodiode array coupled to a thin gadolinium-based granular phosphor screen with a fiber-optic faceplate are investigated. It is shown that this system has a nonlinear response at low detector exposure levels (<10 mR), resulting in an over-estimation of the detective quantum efficiency (DQE) by a factor of two in some cases. Errors in performance metrics on this scale make it difficult to compare new technologies with established systems and predict performance benchmarks that can be achieved in practice and help understand performance bottlenecks. It is shown the CMOS response is described by a power-law model that can be used to linearize image data. Linearization removed an unexpected dependence of the DQE on detector exposure level.

  11. Catechol-based matrix metalloproteinase inhibitors with additional antioxidative activity.

    PubMed

    Tauro, Marilena; Laghezza, Antonio; Loiodice, Fulvio; Piemontese, Luca; Caradonna, Alessia; Capelli, Davide; Montanari, Roberta; Pochetti, Giorgio; Di Pizio, Antonella; Agamennone, Mariangela; Campestre, Cristina; Tortorella, Paolo

    2016-01-01

    New catechol-containing chemical entities have been investigated as matrix metalloproteinase inhibitors as well as antioxidant molecules. The combination of the two properties could represent a useful feature due to the potential application in all the pathological processes characterized by increased proteolytic activity and radical oxygen species (ROS) production, such as inflammation and photoaging. A series of catechol-based molecules were synthesized and tested for both proteolytic and oxidative inhibitory activity, and the detailed binding mode was assessed by crystal structure determination of the complex between a catechol derivative and the matrix metalloproteinase-8. Surprisingly, X-ray structure reveals that the catechol oxygens do not coordinates the zinc atom.

  12. Pixelated neutron image plates

    NASA Astrophysics Data System (ADS)

    Schlapp, M.; Conrad, H.; von Seggern, H.

    2004-09-01

    Neutron image plates (NIPs) have found widespread application as neutron detectors for single-crystal and powder diffraction, small-angle scattering and tomography. After neutron exposure, the image plate can be read out by scanning with a laser. Commercially available NIPs consist of a powder mixture of BaFBr : Eu2+ and Gd2O3 dispersed in a polymer matrix and supported by a flexible polymer sheet. Since BaFBr : Eu2+ is an excellent x-ray storage phosphor, these NIPs are particularly sensitive to ggr-radiation, which is always present as a background radiation in neutron experiments. In this work we present results on NIPs consisting of KCl : Eu2+ and LiF that were fabricated into ceramic image plates in which the alkali halides act as a self-supporting matrix without the necessity for using a polymeric binder. An advantage of this type of NIP is the significantly reduced ggr-sensitivity. However, the much lower neutron absorption cross section of LiF compared with Gd2O3 demands a thicker image plate for obtaining comparable neutron absorption. The greater thickness of the NIP inevitably leads to a loss in spatial resolution of the image plate. However, this reduction in resolution can be restricted by a novel image plate concept in which a ceramic structure with square cells (referred to as a 'honeycomb') is embedded in the NIP, resulting in a pixelated image plate. In such a NIP the read-out light is confined to the particular illuminated pixel, decoupling the spatial resolution from the optical properties of the image plate material and morphology. In this work, a comparison of experimentally determined and simulated spatial resolutions of pixelated and unstructured image plates for a fixed read-out laser intensity is presented, as well as simulations of the properties of these NIPs at higher laser powers.

  13. 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.

  14. Large area CMOS active pixel sensor x-ray imager for digital breast tomosynthesis: Analysis, modeling, and characterization

    SciTech Connect

    Zhao, Chumin; Kanicki, Jerzy; Konstantinidis, Anastasios C.; Patel, Tushita

    2015-11-15

    Purpose: Large area x-ray imagers based on complementary metal-oxide-semiconductor (CMOS) active pixel sensor (APS) technology have been proposed for various medical imaging applications including digital breast tomosynthesis (DBT). The low electronic noise (50–300 e{sup −}) of CMOS APS x-ray imagers provides a possible route to shrink the pixel pitch to smaller than 75 μm for microcalcification detection and possible reduction of the DBT mean glandular dose (MGD). Methods: In this study, imaging performance of a large area (29 × 23 cm{sup 2}) CMOS APS x-ray imager [Dexela 2923 MAM (PerkinElmer, London)] with a pixel pitch of 75 μm was characterized and modeled. The authors developed a cascaded system model for CMOS APS x-ray imagers using both a broadband x-ray radiation and monochromatic synchrotron radiation. The experimental data including modulation transfer function, noise power spectrum, and detective quantum efficiency (DQE) were theoretically described using the proposed cascaded system model with satisfactory consistency to experimental results. Both high full well and low full well (LFW) modes of the Dexela 2923 MAM CMOS APS x-ray imager were characterized and modeled. The cascaded system analysis results were further used to extract the contrast-to-noise ratio (CNR) for microcalcifications with sizes of 165–400 μm at various MGDs. The impact of electronic noise on CNR was also evaluated. Results: The LFW mode shows better DQE at low air kerma (K{sub a} < 10 μGy) and should be used for DBT. At current DBT applications, air kerma (K{sub a} ∼ 10 μGy, broadband radiation of 28 kVp), DQE of more than 0.7 and ∼0.3 was achieved using the LFW mode at spatial frequency of 0.5 line pairs per millimeter (lp/mm) and Nyquist frequency ∼6.7 lp/mm, respectively. It is shown that microcalcifications of 165–400 μm in size can be resolved using a MGD range of 0.3–1 mGy, respectively. In comparison to a General Electric GEN2 prototype DBT system (at

  15. A novel position and time sensing active pixel sensor with field-assisted electron collection for charged particle tracking and electron microscopy

    NASA Astrophysics Data System (ADS)

    De Geronimo, G.; Deptuch, G.; Dragone, A.; Radeka, V.; Rehak, P.; Castoldi, A.; Fazzi, A.; Gatti, E.; Guazzoni, C.; Rijssenbeek, M.; Dulinski, W.; Besson, A.; Deveaux, M.; Winter, M.

    2006-11-01

    A new type of active pixel sensors (APSs) to track charged particles for particle physics experiments or to count number of electrons that cross any pixel at the focal plane of electron microscopes is described. The electric field of desirable shape is created inside the active volume of the pixel introducing the drift component in the movement of the signal electrons towards charge collecting electrodes. The electric field results from the flow of ˜100 mA/cm 2 hole currents within individual pixels of the sensor. The proposed sensor is produced using a standard industrially available complementary metal oxide silicon (CMOS) process. There are two main advantages of the proposed detectors when compared to the present (February 2005) state-of-the-art, i.e. field-free APS sensors. The first advantage of a field-assisted transport mechanism is the reduction of the charge collection time and of the sharing of the signal electrons between adjacent pixels by diffusion. The second advantage is the freedom to use both kinds of MOS transistors within each pixel of the sensor. Thus, the full functional power of CMOS circuits can be embedded in situ. As an example, 16-bit scalers will be implemented in each pixel of the sensor for electron microscopy. The reduced collection time combined with the state-of-the-art electronics within each pixel provides the most complete information about the position and the timing of incident charged particles for particle physics experiments. Position resolution of new sensors was computationally simulated to be a few microns, that is, the same as the resolution of standard APSs. Moreover, the active depth of the sensor and the associate electronics is less than about 20 μm and a thinned down sensor together with its beryllium backing can have a total thickness of less than 0.1% of one radiation length. The reduction of the thickness of the detector reduces the amount of multiple scattering within the detector. The determination of the

  16. CMOS digital pixel sensors: technology and applications

    NASA Astrophysics Data System (ADS)

    Skorka, Orit; Joseph, Dileepan

    2014-04-01

    CMOS active pixel sensor technology, which is widely used these days for digital imaging, is based on analog pixels. Transition to digital pixel sensors can boost signal-to-noise ratios and enhance image quality, but can increase pixel area to dimensions that are impractical for the high-volume market of consumer electronic devices. There are two main approaches to digital pixel design. The first uses digitization methods that largely rely on photodetector properties and so are unique to imaging. The second is based on adaptation of a classical analog-to-digital converter (ADC) for in-pixel data conversion. Imaging systems for medical, industrial, and security applications are emerging lower-volume markets that can benefit from these in-pixel ADCs. With these applications, larger pixels are typically acceptable, and imaging may be done in invisible spectral bands.

  17. The Belle II DEPFET pixel detector

    NASA Astrophysics Data System (ADS)

    Moser, Hans-Günther

    2016-09-01

    The Belle II experiment at KEK (Tsukuba, Japan) will explore heavy flavour physics (B, charm and tau) at the starting of 2018 with unprecedented precision. Charged particles are tracked by a two-layer DEPFET pixel device (PXD), a four-layer silicon strip detector (SVD) and the central drift chamber (CDC). The PXD will consist of two layers at radii of 14 mm and 22 mm with 8 and 12 ladders, respectively. The pixel sizes will vary, between 50 μm×(55-60) μm in the first layer and between 50 μm×(70-85) μm in the second layer, to optimize the charge sharing efficiency. These innermost layers have to cope with high background occupancy, high radiation and must have minimal material to reduce multiple scattering. These challenges are met using the DEPFET technology. Each pixel is a FET integrated on a fully depleted silicon bulk. The signal charge collected in the 'internal gate' modulates the FET current resulting in a first stage amplification and therefore very low noise. This allows very thin sensors (75 μm) reducing the overall material budget of the detector (0.21% X0). Four fold multiplexing of the column parallel readout allows read out a full frame of the pixel matrix in only 20 μs while keeping the power consumption low enough for air cooling. Only the active electronics outside the detector acceptance has to be cooled actively with a two phase CO2 system. Furthermore the DEPFET technology offers the unique feature of an electronic shutter which allows the detector to operate efficiently in the continuous injection mode of superKEKB.

  18. The ALICE Pixel Detector

    NASA Astrophysics Data System (ADS)

    Mercado-Perez, Jorge

    2002-07-01

    The present document is a brief summary of the performed activities during the 2001 Summer Student Programme at CERN under the Scientific Summer at Foreign Laboratories Program organized by the Particles and Fields Division of the Mexican Physical Society (Sociedad Mexicana de Fisica). In this case, the activities were related with the ALICE Pixel Group of the EP-AIT Division, under the supervision of Jeroen van Hunen, research fellow in this group. First, I give an introduction and overview to the ALICE experiment; followed by a description of wafer probing. A brief summary of the test beam that we had from July 13th to July 25th is given as well.

  19. Platelet activation by extracellular matrix proteins in haemostasis and thrombosis.

    PubMed

    Watson, Steve P

    2009-01-01

    The prevention of excessive blood loss to avoid fatal haemorrhage is a pivotal process for all organisms possessing a circulatory system. Increased circulating blood volume and pressure, as required in larger animals, make this process all the more important and challenging. It is essential to have a powerful and rapid system to detect damage and generate an effective seal, and which is also exquisitely regulated to prevent unwanted, excessive or systemic activation so as to avoid blockage of vessels. Thus, a highly specialised and efficient haemostatic system has evolved that consists of cellular (platelets) and protein (coagulation factors) components. Importantly, this is able to support haemostasis in both the low shear environment of the venous system and the high shear environment of the arterial system. Endothelial cells, lining the entire circulation system, play a crucial role in the delicate balance between activation and inhibition of the haemostatic system. An intact and healthy endothelium supports blood flow by preventing attachment of cells and proteins which is required for initiation of coagulation and platelet activation. Endothelial cells produce and release the two powerful soluble inhibitors of platelet activation, nitric oxide and prostacyclin, and express high levels of CD39 which rapidly metabolises the major platelet feedback agonist, ADP. This antithrombotic environment however can rapidly change following activation or removal of endothelial cells through injury or rupture of atherosclerotic plaques. Loss of endothelial cells exposes the subendothelial extracellular matrix which creates strong signals for activation of the haemostatic system including powerful platelet adhesion and activation. Quantitative and qualitative changes in the composition of the subendothelial extracellular matrix influence these prothrombotic characteristics with life threatening thrombotic and bleeding complications, as illustrated by formation of

  20. Analysis and Enhancement of Low-Light-Level Performance of Photodiode-Type CMOS Active Pixel Images Operated with Sub-Threshold Reset

    NASA Technical Reports Server (NTRS)

    Pain, Bedabrata; Yang, Guang; Ortiz, Monico; Wrigley, Christopher; Hancock, Bruce; Cunningham, Thomas

    2000-01-01

    Noise in photodiode-type CMOS active pixel sensors (APS) is primarily due to the reset (kTC) noise at the sense node, since it is difficult to implement in-pixel correlated double sampling for a 2-D array. Signal integrated on the photodiode sense node (SENSE) is calculated by measuring difference between the voltage on the column bus (COL) - before and after the reset (RST) is pulsed. Lower than kTC noise can be achieved with photodiode-type pixels by employing "softreset" technique. Soft-reset refers to resetting with both drain and gate of the n-channel reset transistor kept at the same potential, causing the sense node to be reset using sub-threshold MOSFET current. However, lowering of noise is achieved only at the expense higher image lag and low-light-level non-linearity. In this paper, we present an analysis to explain the noise behavior, show evidence of degraded performance under low-light levels, and describe new pixels that eliminate non-linearity and lag without compromising noise.

  1. 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.

  2. Charge retention characteristics of silicide-induced crystallized polycrystalline silicon floating gate thin-film transistors for active matrix organic light-emitting diode.

    PubMed

    Park, Jae Hyo; Son, Se Wan; Byun, Chang Woo; Kim, Hyung Yoon; Joo, So Na; Lee, Yong Woo; Yun, Seung Jae; Joo, Seung Ki

    2013-10-01

    In this work, non-volatile memory thin-film transistor (NVM-TFT) was fabricated by nickel silicide-induced laterally crystallized (SILC) polycrystalline silicon (poly-Si) as the active layer. The nickel seed silicide-induced crystallized (SIC) poly-Si was used as storage layer which is embedded in the gate insulator. The novel unit pixel of active matrix organic light-emitting diode (AMOLED) using NVM-TFT is proposed and investigated the electrical and optical performance. The threshold voltage shift showed 17.2 V and the high reliability of retention characteristic was demonstrated until 10 years. The retention time can modulate the recharge refresh time of the unit pixel of AMOLED up to 5000 sec.

  3. 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.

  4. 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.

  5. 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.

  6. Noise Characterization of Polycrystalline Silicon Thin Film Transistors for X-ray Imagers Based on Active Pixel Architectures.

    PubMed

    Antonuk, L E; Koniczek, M; McDonald, J; El-Mohri, Y; Zhao, Q; Behravan, M

    2008-01-01

    An examination of the noise of polycrystalline silicon thin film transistors, in the context of flat panel x-ray imager development, is reported. The study was conducted in the spirit of exploring how the 1/f, shot and thermal noise components of poly-Si TFTs, determined from current noise power spectral density measurements, as well as through calculation, can be used to assist in the development of imagers incorporating pixel amplification circuits based on such transistors.

  7. Design and feasibility of active matrix flat panel detector using avalanche amorphous selenium for protein crystallography.

    PubMed

    Sultana, Afrin; Reznik, Alla; Karim, Karim S; Rowlands, J A

    2008-10-01

    Protein crystallography is the most important technique for resolving the three-dimensional atomic structure of protein by measuring the intensity of its x-ray diffraction pattern. This work proposes a large area flat panel detector for protein crystallography based on direct conversion x-ray detection technique using avalanche amorphous selenium (a-Se) as the high gain photoconductor, and active matrix readout using amorphous silicon (a-Si:H) thin film transistors. The detector employs avalanche multiplication phenomenon of a-Se to make the detector sensitive to each incident x ray. The advantages of the proposed detector over the existing imaging plate and charge coupled device detectors are large area, high dynamic range coupled to single x-ray detection capability, fast readout, high spatial resolution, and inexpensive manufacturing process. The optimal detector design parameters (such as detector size, pixel size, and thickness of a-Se layer), and operating parameters (such as electric field across the a-Se layer) are determined based on the requirements for protein crystallography application. The performance of the detector is evaluated in terms of readout time (<1 s), dynamic range (approximately 10(5)), and sensitivity (approximately 1 x-ray photon), thus validating the detector's efficacy for protein crystallography.

  8. ATLAS IBL Pixel Upgrade

    NASA Astrophysics Data System (ADS)

    La Rosa, A.; Atlas Ibl Collaboration

    2011-06-01

    The upgrade for ATLAS detector will undergo different phases towards super-LHC. The first upgrade for the Pixel detector will consist of the construction of a new pixel layer which will be installed during the first shutdown of the LHC machine (LHC phase-I upgrade). The new detector, called Insertable B-Layer (IBL), will be inserted between the existing pixel detector and a new (smaller radius) beam-pipe at a radius of 3.3 cm. The IBL will require the development of several new technologies to cope with increase of radiation or pixel occupancy and also to improve the physics performance which will be achieved by reducing the pixel size and of the material budget. Three different promising sensor technologies (planar-Si, 3D-Si and diamond) are currently under investigation for the pixel detector. An overview of the project with particular emphasis on the pixel module is presented in this paper.

  9. Ramiprilate inhibits functional matrix metalloproteinase activity in Crohn's disease fistulas.

    PubMed

    Efsen, Eva; Saermark, Torben; Hansen, Alastair; Bruun, Eywin; Brynskov, Jørn

    2011-09-01

    Increased expression of matrix metalloproteinase (MMP)-2, -3 and -9 has been demonstrated in Crohn's disease fistulas, but it is unknown whether these enzymes are biologically active and represent a therapeutic target. Therefore, we investigated the proteolytic activity of MMPs in fistula tissue and examined the effect of inhibitors, including clinically available drugs that beside their main action also suppress MMPs. Fistula specimens were obtained by surgical excision from 22 patients with Crohn's disease and from 10 patients with fistulas resulting from other causes. Colonic endoscopic biopsies from six controls were also included. Total functional MMP activity was measured by a high-pressure liquid chromatography (HPLC)-based, fluorogenic MMP-substrate cleavage assay, and the specific activity of MMP-2, -3 and -9 by the MMP Biotrak Activity Assay. The MMP inhibitors comprised ethylene-diamine-tetraacetic acid (EDTA), the synthetic broad-spectrum inhibitor, GM6001, the angiotensin-converting enzyme (ACE) inhibitor, ramiprilate, and the tetracycline, doxycycline. In Crohn's disease fistulas, about 50% of the total protease activity was attributable to MMP activity. The average total MMP activity was significantly higher (about 3.5-times) in Crohn's fistulas (471 FU/μg protein, range 49-2661) compared with non-Crohn's fistulas [134 FU/μg protein, range 0-495, (p < 0.05)] and normal colon [153 FU/μg protein, range 77-243, (p < 0.01)]. MMP-3 activity was increased in Crohn's fistulas (1.4 ng/ml, range 0-9.83) compared with non-Crohn's fistulas, [0.32 ng/ml, range 0-2.66, (p < 0.02)]. The same applied to MMP-9 activity [0.64 ng/ml, range 0-5.66 and 0.17 ng/ml, range 0-1.1, respectively (p < 0.04)]. Ramiprilate significantly decreased the average total MMP activity level by 42% and suppressed the specific MMP-3 activity by 72%, which is comparable to the effect of GM6001 (87%). Moreover, MMP-9 activity was completely blunted by ramiprilate. Doxycycline had no

  10. 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

  11. Bad pixel mapping

    NASA Astrophysics Data System (ADS)

    Smith, Roger M.; Hale, David; Wizinowich, Peter

    2014-07-01

    Bad pixels are generally treated as a loss of useable area and then excluded from averaged performance metrics. The definition and detection of "bad pixels" or "cosmetic defects" are seldom discussed, perhaps because they are considered self-evident or of minor consequence for any scientific grade detector, however the ramifications can be more serious than generally appreciated. While the definition of pixel performance is generally understood, the classification of pixels as useable is highly application-specific, as are the consequences of ignoring or interpolating over such pixels. CMOS sensors (including NIR detectors) exhibit less compact distributions of pixel properties than CCDs. The extended tails in these distributions result in a steeper increase in bad pixel counts as performance thresholds are tightened which comes as a surprise to many users. To illustrate how some applications are much more sensitive to bad pixels than others, we present a bad pixel mapping exercise for the Teledyne H2RG used as the NIR tip-tilt sensor in the Keck-1 Adaptive Optics system. We use this example to illustrate the wide range of metrics by which a pixel might be judged inadequate. These include pixel bump bond connectivity, vignetting, addressing faults in the mux, severe sensitivity deficiency of some pixels, non linearity, poor signal linearity, low full well, poor mean-variance linearity, excessive noise and high dark current. Some pixels appear bad by multiple metrics. We also discuss the importance of distinguishing true performance outliers from measurement errors. We note how the complexity of these issues has ramifications for sensor procurement and acceptance testing strategies.

  12. Amorphous In–Ga–Zn–O thin-film transistor active pixel sensor x-ray imager for digital breast tomosynthesis

    SciTech Connect

    Zhao, Chumin; Kanicki, Jerzy

    2014-09-15

    Purpose: The breast cancer detection rate for digital breast tomosynthesis (DBT) is limited by the x-ray image quality. The limiting Nyquist frequency for current DBT systems is around 5 lp/mm, while the fine image details contained in the high spatial frequency region (>5 lp/mm) are lost. Also today the tomosynthesis patient dose is high (0.67–3.52 mGy). To address current issues, in this paper, for the first time, a high-resolution low-dose organic photodetector/amorphous In–Ga–Zn–O thin-film transistor (a-IGZO TFT) active pixel sensor (APS) x-ray imager is proposed for next generation DBT systems. Methods: The indirect x-ray detector is based on a combination of a novel low-cost organic photodiode (OPD) and a cesium iodide-based (CsI:Tl) scintillator. The proposed APS x-ray imager overcomes the difficulty of weak signal detection, when small pixel size and low exposure conditions are used, by an on-pixel signal amplification with a significant charge gain. The electrical performance of a-IGZO TFT APS pixel circuit is investigated by SPICE simulation using modified Rensselaer Polytechnic Institute amorphous silicon (a-Si:H) TFT model. Finally, the noise, detective quantum efficiency (DQE), and resolvability of the complete system are modeled using the cascaded system formalism. Results: The result demonstrates that a large charge gain of 31–122 is achieved for the proposed high-mobility (5–20 cm{sup 2}/V s) amorphous metal-oxide TFT APS. The charge gain is sufficient to eliminate the TFT thermal noise, flicker noise as well as the external readout circuit noise. Moreover, the low TFT (<10{sup −13} A) and OPD (<10{sup −8} A/cm{sup 2}) leakage currents can further reduce the APS noise. Cascaded system analysis shows that the proposed APS imager with a 75 μm pixel pitch can effectively resolve the Nyquist frequency of 6.67 lp/mm, which can be further improved to ∼10 lp/mm if the pixel pitch is reduced to 50 μm. Moreover, the

  13. 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.

  14. New CMOS digital pixel sensor architecture dedicated to a visual cortical implant

    NASA Astrophysics Data System (ADS)

    Trépanier, Annie; Trépanier, Jean-Luc; Sawan, Mohamad; Audet, Yves

    2004-10-01

    A CMOS image sensor with pixel level analog to digital conversion is presented. Each 16μm x 16μm pixel area contains a photodiode, with a fill factor of 22%, a comparator and an 8-bit DRAM, resulting in a total of 44 transistors per pixel. A digital to analog converter is used to deliver a voltage reference to compare with the pixel voltage for the analog to digital conversion. This sensor is required by a visual cortical stimulator, primarily to capture the image which is dedicated to stimulate the visual cortex of a blind patient. An active range finder system will be added to the implant, requiring the difference information between two images, in order to obtain the 3D information useful to the patient. For this purpose, three selectable operation modes are combined in the same pixel circuit. The linear integration, resulting from image capture at multiple exposure times, allows a high intrascene dynamic range. Random accessibility, in space and time, of the array of sensors is possible with the logarithmic mode. And the new differential mode makes the difference between two consecutive images. The circuit of a pixel has been fabricated in CMOS 0.18μm technology and it is under test to validate the full operation of the 3 modes. Also, a matrix of 45 x 90 pixels is currently being implemented for fabrication.

  15. PixelLearn

    NASA Technical Reports Server (NTRS)

    Mazzoni, Dominic; Wagstaff, Kiri; Bornstein, Benjamin; Tang, Nghia; Roden, Joseph

    2006-01-01

    PixelLearn is an integrated user-interface computer program for classifying pixels in scientific images. Heretofore, training a machine-learning algorithm to classify pixels in images has been tedious and difficult. PixelLearn provides a graphical user interface that makes it faster and more intuitive, leading to more interactive exploration of image data sets. PixelLearn also provides image-enhancement controls to make it easier to see subtle details in images. PixelLearn opens images or sets of images in a variety of common scientific file formats and enables the user to interact with several supervised or unsupervised machine-learning pixel-classifying algorithms while the user continues to browse through the images. The machinelearning algorithms in PixelLearn use advanced clustering and classification methods that enable accuracy much higher than is achievable by most other software previously available for this purpose. PixelLearn is written in portable C++ and runs natively on computers running Linux, Windows, or Mac OS X.

  16. A column level, low power, 1 M sample/s double ramp A/D converter for monolithic active pixel sensors in high energy physics

    NASA Astrophysics Data System (ADS)

    Pillet, N.; Heini, S.; Hu, Y.

    2010-08-01

    Monolithic active pixel sensors (MAPS) using standard low cost CMOS technologies available from industrial manufacturers have demonstrated excellent tracking performances for minimum ionizing particles. The need for highly granular, fast, thin sensors with a full digital output drives an R&D effort, aiming to design and optimize a low power high speed A/D converter integrated at the column level. Following this main issue, a double digital ramp A/D converter has been proposed for CMOS monolithic active pixel sensors in this paper. This A/D converter responds to the constraints of size, power dissipation and precision for CMOS sensors for particle detection. It also represents a first step in order to reach the high speed of conversion needed for this kind of application. The A/D converter has a resolution of 4 bits for conversion speed of 1 M sample/s with only 264 μW of static consumption in a very particular pitch of 25 μm×900 μm.

  17. Readability evaluation of an active matrix electrophoric ink display

    NASA Astrophysics Data System (ADS)

    Meyer, Frederick M.; Trissell, Terry L.; Aleva, Denise L.; Longo, Sam J.; Hopper, Darrel G.

    2006-05-01

    A low-power, yet sunlight readable, display is needed for dismounted applications where the user must carry the power source. Such a display could potentially replace paper checklists and maps with electronic counterparts. A reflective active matrix electrophoretic ink display (AMEPID) was evaluated as a candidate technology for such applications. This display technology uses ambient illumination, rather than competing with it, and requires power only when rewriting the display. The device was tested for viewability under a variety of lighting conditions. Readability of displayed text, as compared to standard print on white paper, was evaluated in an indoor office environment and in outdoor lighting conditions. Viewability of the display with night vision goggles (NVGs) was evaluated under simulated full moon, starlight, and overcast illumination conditions. Objective measurements of luminance, contrast ratio and reflectance were conducted under corresponding irradiance conditions and viewing angles using state-of-the-art photometric and radiometric measurement equipment. In addition to visible spectrum measurements, infrared (IR) reflectance and contrast were measured for the extended spectrum of 720-1700 nm. Results are discussed in terms of performance criteria for military displays, which are often much more demanding than for civil applications.

  18. Matrix Metalloproteinase 9 Exerts Antiviral Activity against Respiratory Syncytial Virus

    PubMed Central

    Dabo, Abdoulaye J.; Cummins, Neville; Eden, Edward; Geraghty, Patrick

    2015-01-01

    Increased lung levels of matrix metalloproteinase 9 (MMP9) are frequently observed during respiratory syncytial virus (RSV) infection and elevated MMP9 concentrations are associated with severe disease. However little is known of the functional role of MMP9 during lung infection with RSV. To determine whether MMP9 exerted direct antiviral potential, active MMP9 was incubated with RSV, which showed that MMP9 directly prevented RSV infectivity to airway epithelial cells. Using knockout mice the effect of the loss of Mmp9 expression was examined during RSV infection to demonstrate MMP9’s role in viral clearance and disease progression. Seven days following RSV infection, Mmp9-/- mice displayed substantial weight loss, increased RSV-induced airway hyperresponsiveness (AHR) and reduced clearance of RSV from the lungs compared to wild type mice. Although total bronchoalveolar lavage fluid (BALF) cell counts were similar in both groups, neutrophil recruitment to the lungs during RSV infection was significantly reduced in Mmp9-/- mice. Reduced neutrophil recruitment coincided with diminished RANTES, IL-1β, SCF, G-CSF expression and p38 phosphorylation. Induction of p38 signaling was required for RANTES and G-CSF expression during RSV infection in airway epithelial cells. Therefore, MMP9 in RSV lung infection significantly enhances neutrophil recruitment, cytokine production and viral clearance while reducing AHR. PMID:26284919

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

    PubMed

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

    2007-12-01

    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 (r2 > 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(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(max)) satisfied [chi] < or = 1 on average across the cases that were tested.

  20. 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.

  1. Sub-pixel mapping of water boundaries using pixel swapping algorithm (case study: Tagliamento River, Italy)

    NASA Astrophysics Data System (ADS)

    Niroumand-Jadidi, Milad; Vitti, Alfonso

    2015-10-01

    Taking the advantages of remotely sensed data for mapping and monitoring of water boundaries is of particular importance in many different management and conservation activities. Imagery data are classified using automatic techniques to produce maps entering the water bodies' analysis chain in several and different points. Very commonly, medium or coarse spatial resolution imagery is used in studies of large water bodies. Data of this kind is affected by the presence of mixed pixels leading to very outstanding problems, in particular when dealing with boundary pixels. A considerable amount of uncertainty inescapably occurs when conventional hard classifiers (e.g., maximum likelihood) are applied on mixed pixels. In this study, Linear Spectral Mixture Model (LSMM) is used to estimate the proportion of water in boundary pixels. Firstly by applying an unsupervised clustering, the water body is identified approximately and a buffer area considered ensuring the selection of entire boundary pixels. Then LSMM is applied on this buffer region to estimate the fractional maps. However, resultant output of LSMM does not provide a sub-pixel map corresponding to water abundances. To tackle with this problem, Pixel Swapping (PS) algorithm is used to allocate sub-pixels within mixed pixels in such a way to maximize the spatial proximity of sub-pixels and pixels in the neighborhood. The water area of two segments of Tagliamento River (Italy) are mapped in sub-pixel resolution (10m) using a 30m Landsat image. To evaluate the proficiency of the proposed approach for sub-pixel boundary mapping, the image is also classified using a conventional hard classifier. A high resolution image of the same area is also classified and used as a reference for accuracy assessment. According to the results, sub-pixel map shows in average about 8 percent higher overall accuracy than hard classification and fits very well in the boundaries with the reference map.

  2. High density pixel array

    NASA Technical Reports Server (NTRS)

    Wiener-Avnear, Eliezer (Inventor); McFall, James Earl (Inventor)

    2004-01-01

    A pixel array device is fabricated by a laser micro-milling method under strict process control conditions. The device has an array of pixels bonded together with an adhesive filling the grooves between adjacent pixels. The array is fabricated by moving a substrate relative to a laser beam of predetermined intensity at a controlled, constant velocity along a predetermined path defining a set of grooves between adjacent pixels so that a predetermined laser flux per unit area is applied to the material, and repeating the movement for a plurality of passes of the laser beam until the grooves are ablated to a desired depth. The substrate is of an ultrasonic transducer material in one example for fabrication of a 2D ultrasonic phase array transducer. A substrate of phosphor material is used to fabricate an X-ray focal plane array detector.

  3. Determination of the detective quantum efficiency of a prototype, megavoltage indirect detection, active matrix flat-panel imager.

    PubMed

    El-Mohri, Y; Jee, K W; Antonuk, L E; Maolinbay, M; Zhao, Q

    2001-12-01

    After years of aggressive development, active matrix flat-panel imagers (AMFPIs) have recently become commercially available for radiotherapy imaging. In this paper we report on a comprehensive evaluation of the signal and noise performance of a large-area prototype AMFPI specifically developed for this application. The imager is based on an array of 512 x 512 pixels incorporating amorphous silicon photodiodes and thin-film transistors offering a 26 x 26 cm2 active area at a pixel pitch of 508 microm. This indirect detection array was coupled to various x-ray converters consisting of a commercial phosphor screen (Lanex Fast B, Lanex Regular, or Lanex Fine) and a 1 mm thick copper plate. Performance of the imager in terms of measured sensitivity, modulation transfer function (MTF), noise power spectra (NPS), and detective quantum efficiency (DQE) is reported at beam energies of 6 and 15 MV and at doses of 1 and 2 monitor units (MU). In addition, calculations of system performance (NPS, DQE) based on cascaded-system formalism were reported and compared to empirical results. In these calculations, the Swank factor and spatial energy distributions of secondary electrons within the converter were modeled by means of EGS4 Monte Carlo simulations. Measured MTFs of the system show a weak dependence on screen type (i.e., thickness), which is partially due to the spreading of secondary radiation. Measured DQE was found to be independent of dose for the Fast B screen, implying that the imager is input-quantum-limited at 1 MU, even at an extended source-to-detector distance of 200 cm. The maximum DQE obtained is around 1%--a limit imposed by the low detection efficiency of the converter. For thinner phosphor screens, the DQE is lower due to their lower detection efficiencies. Finally, for the Fast B screen, good agreement between calculated and measured DQE was observed.

  4. 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

  5. Time-resolved Emission from Bright Hot Pixels of an Active Region Observed in the EUV Band with SDO/AIA and Multi-stranded Loop Modeling

    NASA Astrophysics Data System (ADS)

    Tajfirouze, E.; Reale, F.; Petralia, A.; Testa, P.

    2016-01-01

    Evidence of small amounts of very hot plasma has been found in active regions and might be an indication of impulsive heating released at spatial scales smaller than the cross-section of a single loop. We investigate the heating and substructure of coronal loops in the core of one such active region by analyzing the light curves in the smallest resolution elements of solar observations in two EUV channels (94 and 335 Å) from the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory. We model the evolution of a bundle of strands heated by a storm of nanoflares by means of a hydrodynamic 0D loop model (EBTEL). The light curves obtained from a random combination of those of single strands are compared to the observed light curves either in a single pixel or in a row of pixels, simultaneously in the two channels, and using two independent methods: an artificial intelligent system (Probabilistic Neural Network) and a simple cross-correlation technique. We explore the space of the parameters to constrain the distribution of the heat pulses, their duration, their spatial size, and, as a feedback on the data, their signatures on the light curves. From both methods the best agreement is obtained for a relatively large population of events (1000) with a short duration (less than 1 minute) and a relatively shallow distribution (power law with index 1.5) in a limited energy range (1.5 decades). The feedback on the data indicates that bumps in the light curves, especially in the 94 Å channel, are signatures of a heating excess that occurred a few minutes before.

  6. TIME-RESOLVED EMISSION FROM BRIGHT HOT PIXELS OF AN ACTIVE REGION OBSERVED IN THE EUV BAND WITH SDO/AIA AND MULTI-STRANDED LOOP MODELING

    SciTech Connect

    Tajfirouze, E.; Reale, F.; Petralia, A.; Testa, P.

    2016-01-01

    Evidence of small amounts of very hot plasma has been found in active regions and might be an indication of impulsive heating released at spatial scales smaller than the cross-section of a single loop. We investigate the heating and substructure of coronal loops in the core of one such active region by analyzing the light curves in the smallest resolution elements of solar observations in two EUV channels (94 and 335 Å) from the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory. We model the evolution of a bundle of strands heated by a storm of nanoflares by means of a hydrodynamic 0D loop model (EBTEL). The light curves obtained from a random combination of those of single strands are compared to the observed light curves either in a single pixel or in a row of pixels, simultaneously in the two channels, and using two independent methods: an artificial intelligent system (Probabilistic Neural Network) and a simple cross-correlation technique. We explore the space of the parameters to constrain the distribution of the heat pulses, their duration, their spatial size, and, as a feedback on the data, their signatures on the light curves. From both methods the best agreement is obtained for a relatively large population of events (1000) with a short duration (less than 1 minute) and a relatively shallow distribution (power law with index 1.5) in a limited energy range (1.5 decades). The feedback on the data indicates that bumps in the light curves, especially in the 94 Å channel, are signatures of a heating excess that occurred a few minutes before.

  7. Fiber pixelated image database

    NASA Astrophysics Data System (ADS)

    Shinde, Anant; Perinchery, Sandeep Menon; Matham, Murukeshan Vadakke

    2016-08-01

    Imaging of physically inaccessible parts of the body such as the colon at micron-level resolution is highly important in diagnostic medical imaging. Though flexible endoscopes based on the imaging fiber bundle are used for such diagnostic procedures, their inherent honeycomb-like structure creates fiber pixelation effects. This impedes the observer from perceiving the information from an image captured and hinders the direct use of image processing and machine intelligence techniques on the recorded signal. Significant efforts have been made by researchers in the recent past in the development and implementation of pixelation removal techniques. However, researchers have often used their own set of images without making source data available which subdued their usage and adaptability universally. A database of pixelated images is the current requirement to meet the growing diagnostic needs in the healthcare arena. An innovative fiber pixelated image database is presented, which consists of pixelated images that are synthetically generated and experimentally acquired. Sample space encompasses test patterns of different scales, sizes, and shapes. It is envisaged that this proposed database will alleviate the current limitations associated with relevant research and development and would be of great help for researchers working on comb structure removal algorithms.

  8. Selecting Pixels for Kepler Downlink

    NASA Technical Reports Server (NTRS)

    Bryson, Stephen T.; Jenkins, Jon M.; Klaus, Todd C.; Cote, Miles T.; Quintana, Elisa V.; Hall, Jennifer R.; Ibrahim, Khadeejah; Chandrasekaran, Hema; Caldwell, Douglas A.; Van Cleve, Jeffrey E.; Haas, Michael R.

    2010-01-01

    The Kepler mission monitors > 100,000 stellar targets using 42 2200 1024 pixel CCDs. Bandwidth constraints prevent the downlink of all 96 million pixels per 30-minute cadence, so the Kepler spacecraft downlinks a specified collection of pixels for each target. These pixels are selected by considering the object brightness, background and the signal-to-noise of each pixel, and are optimized to maximize the signal-to-noise ratio of the target. This paper describes pixel selection, creation of spacecraft apertures that efficiently capture selected pixels, and aperture assignment to a target. Diagnostic apertures, short-cadence targets and custom specified shapes are discussed.

  9. Illuminant spectrum estimation at a pixel.

    PubMed

    Ratnasingam, Sivalogeswaran; Hernández-Andrés, Javier

    2011-04-01

    In this paper, an algorithm is proposed to estimate the spectral power distribution of a light source at a pixel. The first step of the algorithm is forming a two-dimensional illuminant invariant chromaticity space. In estimating the illuminant spectrum, generalized inverse estimation and Wiener estimation methods were applied. The chromaticity space was divided into small grids and a weight matrix was used to estimate the illuminant spectrum illuminating the pixels that fall within a grid. The algorithm was tested using a different number of sensor responses to determine the optimum number of sensors for accurate colorimetric and spectral reproduction. To investigate the performance of the algorithm realistically, the responses were multiplied with Gaussian noise and then quantized to 10 bits. The algorithm was tested with standard and measured data. Based on the results presented, the algorithm can be used with six sensors to obtain a colorimetrically good estimate of the illuminant spectrum at a pixel.

  10. 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.

  11. 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

  12. A neighbor pixel communication filtering structure for Dynamic Vision Sensors

    NASA Astrophysics Data System (ADS)

    Xu, Yuan; Liu, Shiqi; Lu, Hehui; Zhang, Zilong

    2017-02-01

    For Dynamic Vision Sensors (DVS), thermal noise and junction leakage current induced Background Activity (BA) is the major cause of the deterioration of images quality. Inspired by the smoothing filtering principle of horizontal cells in vertebrate retina, A DVS pixel with Neighbor Pixel Communication (NPC) filtering structure is proposed to solve this issue. The NPC structure is designed to judge the validity of pixel's activity through the communication between its 4 adjacent pixels. The pixel's outputs will be suppressed if its activities are determined not real. The proposed pixel's area is 23.76×24.71μm2 and only 3ns output latency is introduced. In order to validate the effectiveness of the structure, a 5×5 pixel array has been implemented in SMIC 0.13μm CIS process. 3 test cases of array's behavioral model show that the NPC-DVS have an ability of filtering the BA.

  13. 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.

  14. 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

  15. 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

  16. Fully Screen-Printed, Large-Area, and Flexible Active-Matrix Electrochromic Displays Using Carbon Nanotube Thin-Film Transistors.

    PubMed

    Cao, Xuan; Lau, Christian; Liu, Yihang; Wu, Fanqi; Gui, Hui; Liu, Qingzhou; Ma, Yuqiang; Wan, Haochuan; Amer, Moh R; Zhou, Chongwu

    2016-11-22

    Semiconducting single-wall carbon nanotubes are ideal semiconductors for printed electronics due to their advantageous electrical and mechanical properties, intrinsic printability in solution, and desirable stability in air. However, fully printed, large-area, high-performance, and flexible carbon nanotube active-matrix backplanes are still difficult to realize for future displays and sensing applications. Here, we report fully screen-printed active-matrix electrochromic displays employing carbon nanotube thin-film transistors. Our fully printed backplane shows high electrical performance with mobility of 3.92 ± 1.08 cm(2) V(-1) s(-1), on-off current ratio Ion/Ioff ∼ 10(4), and good uniformity. The printed backplane was then monolithically integrated with an array of printed electrochromic pixels, resulting in an entirely screen-printed active-matrix electrochromic display (AMECD) with good switching characteristics, facile manufacturing, and long-term stability. Overall, our fully screen-printed AMECD is promising for the mass production of large-area and low-cost flexible displays for applications such as disposable tags, medical electronics, and smart home appliances.

  17. Matrix formulation of the surface-enhanced Raman optical activity theory

    NASA Astrophysics Data System (ADS)

    Bouř, Petr

    2007-04-01

    The surface-enhanced Raman optical activity theory [J. Chem. Phys.125, 124704 (2006)] is formulated in a matrix form, which makes the formalism simpler and allows to extend it for more complicated colloid and molecular systems.

  18. "Click" synthesis of small molecule probes for activity-based fingerprinting of matrix metalloproteases.

    PubMed

    Wang, Jun; Uttamchandani, Mahesh; Li, Junqi; Hu, Mingyu; Yao, Shao Q

    2006-09-28

    By using "Click Chemistry", we achieved the facile synthesis of various affinity-based hydroxamate probes that enable generation of activity-based fingerprints of a variety of metalloproteases, including matrix metalloproteases (MMPs), in proteomics experiments.

  19. Planar slim-edge pixel sensors for the ATLAS upgrades

    NASA Astrophysics Data System (ADS)

    Altenheiner, S.; Goessling, C.; Jentzsch, J.; Klingenberg, R.; Lapsien, T.; Muenstermann, D.; Rummler, A.; Troska, G.; Wittig, T.

    2012-02-01

    The ATLAS detector at CERN is a general-purpose experiment at the Large Hadron Collider (LHC). The ATLAS Pixel Detector is the innermost tracking detector of ATLAS and requires a sufficient level of hermeticity to achieve superb track reconstruction performance. The current planar n-type pixel sensors feature a pixel matrix of n+-implantations which is (on the opposite p-side) surrounded by so-called guard rings to reduce the high voltage stepwise towards the cutting edge and an additional safety margin. Because of the inactive region around the active area, the sensor modules have been shingled on top of each other's edge which limits the thermal performance and adds complexity in the present detector. The first upgrade phase of the ATLAS pixel detector will consist of the insertable b-layer (IBL), an additional b-layer which will be inserted into the present detector in 2013. Several changes in the sensor design with respect to the existing detector had to be applied to comply with the IBL's specifications and are described in detail. A key issue for the ATLAS upgrades is a flat arrangement of the sensors. To maintain the required level of hermeticity in the detector, the inactive sensor edges have to be reduced to minimize the dead space between the adjacent detector modules. Unirradiated and irradiated sensors with the IBL design have been operated in test beams to study the efficiency performance in the sensor edge region and it was found that the inactive edge width could be reduced from 1100 μm to less than 250 μm.

  20. Biotransformation and adsorption of pharmaceutical and personal care products by activated sludge after correcting matrix effects.

    PubMed

    Deng, Yu; Li, Bing; Yu, Ke; Zhang, Tong

    2016-02-15

    This study reported significant suppressive matrix effects in analyses of six pharmaceutical and personal care products (PPCPs) in activated sludge, sterilized activated sludge and untreated sewage by ultra-performance liquid chromatography-tandem mass spectrometry. Quantitative matrix evaluation on selected PPCPs supplemented the limited quantification data of matrix effects on mass spectrometric determination of PPCPs in complex environment samples. The observed matrix effects were chemical-specific and matrix-dependent, with the most pronounced average effect (-55%) was found on sulfadiazine in sterilized activated sludge. After correcting the matrix effects by post-spiking known amount of PPCPs, the removal mechanisms and biotransformation kinetics of selected PPCPs in activated sludge system were revealed by batch experiment. Experimental data elucidated that the removal of target PPCPs in the activated sludge process was mainly by biotransformation while contributions of adsorption, hydrolysis and volatilization could be neglected. High biotransformation efficiency (52%) was observed on diclofenac while other three compounds (sulfadiazine, sulfamethoxazole and roxithromycin) were partially biotransformed by ~40%. The other two compounds, trimethoprim and carbamazepine, showed recalcitrant to biotransformation of the activated sludge.

  1. The ALPIDE pixel sensor chip for the upgrade of the ALICE Inner Tracking System

    NASA Astrophysics Data System (ADS)

    Aglieri Rinella, Gianluca

    2017-02-01

    The ALPIDE chip is a CMOS Monolithic Active Pixel Sensor being developed for the Upgrade of the ITS of the ALICE experiment at the CERN Large Hadron Collider. The ALPIDE chip is implemented with a 180 nm CMOS Imaging Process and fabricated on substrates with a high-resistivity epitaxial layer. It measures 15 mm×30 mm and contains a matrix of 512×1024 pixels with in-pixel amplification, shaping, discrimination and multi-event buffering. The readout of the sensitive matrix is hit driven. There is no signaling activity over the matrix if there are no hits to read out and power consumption is proportional to the occupancy. The sensor meets the experimental requirements of detection efficiency above 99%, fake-hit probability below 10-5 and a spatial resolution of 5 μm. The capability to read out Pb-Pb interactions at 100 kHz is provided. The power density of the ALPIDE chip is projected to be less than 35 mW/cm2 for the application in the Inner Barrel Layers and below 20 mW/cm2 for the Outer Barrel Layers, where the occupancy is lower. This contribution describes the architecture and the main features of the final ALPIDE chip, planned for submission at the beginning of 2016. Early results from the experimental qualification of full scale prototype predecessors are also reported.

  2. Image quality affected by diffraction of aperture structure arrangement in transparent active-matrix organic light-emitting diode displays.

    PubMed

    Tsai, Yu-Hsiang; Huang, Mao-Hsiu; Jeng, Wei-de; Huang, Ting-Wei; Lo, Kuo-Lung; Ou-Yang, Mang

    2015-10-01

    Transparent display is one of the main technologies in next-generation displays, especially for augmented reality applications. An aperture structure is attached on each display pixel to partition them into transparent and black regions. However, diffraction blurs caused by the aperture structure typically degrade the transparent image when the light from a background object passes through finite aperture window. In this paper, the diffraction effect of an active-matrix organic light-emitting diode display (AMOLED) is studied. Several aperture structures have been proposed and implemented. Based on theoretical analysis and simulation, the appropriate aperture structure will effectively reduce the blur. The analysis data are also consistent with the experimental results. Compared with the various transparent aperture structure on AMOLED, diffraction width (zero energy position of diffraction pattern) of the optimize aperture structure can be reduced 63% and 31% in the x and y directions in CASE 3. Associated with a lenticular lens on the aperture structure, the improvement could reach to 77% and 54% of diffraction width in the x and y directions. Modulation transfer function and practical images are provided to evaluate the improvement of image blurs.

  3. The Dexela 2923 CMOS X-ray detector: A flat panel detector based on CMOS active pixel sensors for medical imaging applications

    NASA Astrophysics Data System (ADS)

    Konstantinidis, Anastasios C.; Szafraniec, Magdalena B.; Speller, Robert D.; Olivo, Alessandro

    2012-10-01

    Complementary metal-oxide-semiconductors (CMOS) active pixel sensors (APS) have been introduced recently in many scientific applications. This work reports on the performance (in terms of signal and noise transfer) of an X-ray detector that uses a novel CMOS APS which was developed for medical X-ray imaging applications. For a full evaluation of the detector's performance, electro-optical and X-ray characterizations were carried out. The former included measuring read noise, full well capacity and dynamic range. The latter, which included measuring X-ray sensitivity, presampling modulation transfer function (pMTF), noise power spectrum (NPS) and the resulting detective quantum efficiency (DQE), was assessed under three beam qualities (28 kV, 50 kV (RQA3) and 70 kV (RQA5) using W/Al) all in accordance with the IEC standard. The detector features an in-pixel option for switching the full well capacity between two distinct modes, high full well (HFW) and low full well (LFW). Two structured CsI:Tl scintillators of different thickness (a “thin” one for high resolution and a thicker one for high light efficiency) were optically coupled to the sensor array to optimize the performance of the system for different medical applications. The electro-optical performance evaluation of the sensor results in relatively high read noise (∼360 e-), high full well capacity (∼1.5×106 e-) and wide dynamic range (∼73 dB) under HFW mode operation. When the LFW mode is used, the read noise is lower (∼165) at the expense of a reduced full well capacity (∼0.5×106 e-) and dynamic range (∼69 dB). The maximum DQE values at low frequencies (i.e. 0.5 lp/mm) are high for both HFW (0.69 for 28 kV, 0.71 for 50 kV and 0.75 for 70 kV) and LFW (0.69 for 28 kV and 0.7 for 50 kV) modes. The X-ray performance of the studied detector compares well to that of other mammography and general radiography systems, obtained under similar experimental conditions. This demonstrates the suitability

  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. Mechanophore activation in a crosslinked polymer matrix via instrumented indentation

    NASA Astrophysics Data System (ADS)

    Davis, Chelsea; Forster, Aaron; Woodcock, Jeremiah; Wang, Muzhou; Gilman, Jeffrey; Material Measurement Laboratory Team

    Recent advances in mechanically-activated fluorophores will enable a host of unique scientific challenges and opportunities to be addressed. Several mechanophores (MPs) in polymers have been reported, yet the specific deformation required to activate these molecules in a bulk polymer network has not been sufficiently specified. In an effort to develop the mechano-activation/deformation relationship of a spirolactam-based MP, scratches were applied to a MP-functionalized glassy crosslinked material at varying normal loads and lateral displacement rates. This experimental design allowed strain and strain rate effects to be decoupled. The fluorescence activation was then observed with a laser scanning confocal microscope. Areas of elastic and plastic deformation as well as brittle fracture were observed within each scratch as the normal loading of the indenter increased. The fluorescence intensity increased with increasing strain. Contact mechanics models are employed to demonstrate that relatively high degrees of strain are required to initiate the ring-opening activation transition within the spirolactam-based MP. These self-reporting damage sensors can be incorporated within polymeric coatings to allow real time structural health monitoring for a myriad of applications.

  6. Plasma matrix metalloproteinase-9 activity in cats with lymphoma.

    PubMed

    Tamamoto, T; Ohno, K; Takahashi, M; Fukushima, K; Kanemoto, H; Fujino, Y; Tsujimoto, H

    2017-03-01

    In this study, plasma MMP-9 activity was evaluated in cats with lymphoma. Plasma samples were obtained from 26 cats with lymphoma before treatment. From 13 of the included 26 cats, plasma samples were obtained 4 weeks after the initiation of treatment. Plasma samples were also obtained from 10 healthy cats as a control. Plasma MMP-9 activity was examined by gelatin zymography and semi-quantitative value (arbitrary unit; a.u.) for each sample was calculated. Relatively high levels of MMP-9 were observed in cats with lymphoma compared with those in healthy control cats. MMP-9 quantification through zymography showed significantly higher activity in cats with lymphoma (median, 0.63 a.u.; range, 0.23-3.24 a.u.) than in healthy controls (0.22 a.u.; 0.12-0.46 a.u.; P < 0.01). MMP-9 activities were significantly different before (0.73 a.u.; 0.30-3.24 a.u.) and after treatment (0.50 a.u.; 0.14-1.32 a.u.; P = 0.017). Measuring plasma MMP-9 activity in cats with lymphoma may become an appropriate monitoring tool for feline lymphoma.

  7. Bovine dentine organic matrix down-regulates osteoclast activity.

    PubMed

    Sriarj, Wantida; Aoki, Kazuhiro; Ohya, Keiichi; Takagi, Yuzo; Shimokawa, Hitoyata

    2009-01-01

    Physiological root resorption is a phenomenon that normally takes place in deciduous teeth; root resorption of permanent teeth occurs only under pathological conditions. The molecular mechanisms underlying these processes are still unclear. Our previous study showed that osteoclasts cultured on deciduous dentine exhibited a higher degree of resorption and higher levels of cathepsin K and MMP-9 mRNA than osteoclasts cultured on permanent dentine. These results could be because of different susceptibilities to acid and the different organic matrices between deciduous and permanent dentine. Thus, the purpose of this study was to investigate the effect of dentine extracts from bovine deciduous and permanent dentine on osteoclast activity. Osteoclasts, obtained from mouse bone marrow cells co-cultured with an osteoblast-rich fraction in the presence of 1,25-(OH)(2)-vitamin D3 and PGE2, were incubated with or without 0.6 M HCl extracts from bovine deciduous or permanent dentine for 48 h. TRAP positive cell number, TRAP activity, the areas of resorption pits, and mRNA levels of TRAP, v-ATPase, calcitonin receptor, cathepsin K, and MMP-9 were examined. The results illustrated that TRAP activity, the resorbed area, and the mRNA levels of osteoclast marker genes seemed to be suppressed by both deciduous and permanent dentine extracts. These findings indicate that some factors that suppress osteoclast activity are contained in both deciduous and permanent dentine extracts. Although there was no significant difference in osteoclast activity between deciduous and permanent dentine extracts, osteoclasts incubated with permanent dentine extracts tend to exhibit less resorption activity than those incubated with deciduous dentine extracts. However, we could not clearly explain the causes of this.

  8. Immobilization of cesium in alkaline activated fly ash matrix

    NASA Astrophysics Data System (ADS)

    Fernandez-Jimenez, A.; Macphee, D. E.; Lachowski, E. E.; Palomo, A.

    2005-11-01

    The immobilization potential of alkaline activated fly ash (AAFA) matrices for cesium has been investigated. The presence of Cs in the AAFA pastes, prepared using 8M NaOH solution as activator, showed no significant adverse effects on mechanical strength or microstructure, nor were significant quantities of Cs leached following application of the Toxic Characteristic Leaching Procedure (TCLP) and American Nuclear Society (ANS) 16.1 leaching protocols. Microstructural analysis shows Cs associated with the main reaction product in the AAFA suggesting that cesium is chemically bound rather than physically encapsulated. It is proposed that cesium is incorporated into the alkaline aluminosilicate gel, a precursor for zeolite formation.

  9. Method and apparatus of high dynamic range image sensor with individual pixel reset

    NASA Technical Reports Server (NTRS)

    Yadid-Pecht, Orly (Inventor); Pain, Bedabrata (Inventor); Fossum, Eric R. (Inventor)

    2001-01-01

    A wide dynamic range image sensor provides individual pixel reset to vary the integration time of individual pixels. The integration time of each pixel is controlled by column and row reset control signals which activate a logical reset transistor only when both signals coincide for a given pixel.

  10. Strategies to improve the signal and noise performance of active matrix, flat-panel imagers for diagnostic x-ray applications.

    PubMed

    Antonuk, L E; Jee, K W; El-Mohri, Y; Maolinbay, M; Nassif, S; Rong, X; Zhao, Q; Siewerdsen, J H; Street, R A; Shah, K S

    2000-02-01

    A theoretical investigation of factors limiting the detective quantum efficiency (DQE) of active matrix flat-panel imagers (AMFPIs), and of methods to overcome these limitations, is reported. At the higher exposure levels associated with radiography, the present generation of AMFPIs is capable of exhibiting DQE performance equivalent, or superior, to that of existing film-screen and computed radiography systems. However, at exposure levels commonly encountered in fluoroscopy, AMFPIs exhibit significantly reduced DQE and this problem is accentuated at higher spatial frequencies. The problem applies both to AMFPIs that rely on indirect detection as well as direct detection of the incident radiation. This reduced performance derives from the relatively large magnitude of the square of the total additive noise compared to the system gain for existing AMFPIs. In order to circumvent these restrictions, a variety of strategies to decrease additive noise and enhance system gain are proposed. Additive noise could be reduced through improved preamplifier, pixel and array design, including the incorporation of compensation lines to sample external line noise. System gain could be enhanced through the use of continuous photodiodes, pixel amplifiers, or higher gain x-ray converters such as lead iodide. The feasibility of these and other strategies is discussed and potential improvements to DQE performance are quantified through a theoretical investigation of a variety of hypothetical 200 microm pitch designs. At low exposures, such improvements could greatly increase the magnitude of the low spatial frequency component of the DQE, rendering it practically independent of exposure while simultaneously reducing the falloff in DQE at higher spatial frequencies. Furthermore, such noise reduction and gain enhancement could lead to the development of AMFPIs with high DQE performance which are capable of providing both high resolution radiographic images, at approximately 100 microm

  11. Investigation of the signal behavior at diagnostic energies of prototype, direct detection, active matrix, flat-panel imagers incorporating polycrystalline HgI2

    PubMed Central

    Du, Hong; El-Mohri, Youcef; Zhao, Qihua; Su, Zhong; Yamamoto, Jin; Wang, Yi

    2009-01-01

    Active matrix, flat-panel x-ray imagers based on a-Si:H thin film transistors offer many advantages and are widely utilized in medical imaging applications. Unfortunately, the detective quantum efficiency (DQE) of conventional flat-panel imagers incorporating scintillators or a-Se photoconductors is significantly limited by their relatively modest signal to noise ratio, particularly in applications involving low x-ray exposures or high spatial resolution. For this reason, polycrystalline HgI2 is of considerable interest by virtue of its low effective work function, high atomic number, and the possibility of large-area deposition. In this study, a detailed investigation of the properties of prototype, flat-panel arrays coated with two forms of this high-gain photoconductor are reported. Encouragingly, high x-ray sensitivity, low dark current, and spatial resolution close to the theoretical limits were observed from a number of prototypes. In addition, input-quantum-limited DQE performance was measured from one of the prototypes at relatively low exposures. However, high levels of charge trapping, lag, and polarization, as well as pixel-to-pixel variations in x-ray sensitivity are of concern. While the results of the current study are promising, further development will be required to realize prototypes exhibiting the characteristics necessary to allow practical implementation of this approach. PMID:18296765

  12. Differential metabolic activity in the striosome and matrix compartments of the rat striatum during natural behaviors.

    PubMed

    Brown, Lucy L; Feldman, Samuel M; Smith, Diane M; Cavanaugh, James R; Ackermann, Robert F; Graybiel, Ann M

    2002-01-01

    The striosome and matrix compartments of the striatum are clearly identified by their neurochemical expression patterns and anatomical connections. To determine whether these compartments are distinguishable functionally, we used [14C]deoxyglucose metabolic mapping in the rat and tested whether neutral behavioral states (free movement, gentle restraint, and focal tactile stimulation under gentle restraint) were associated with regions of high metabolic activity in the matrix, in striosomes, or in both. We identified metabolic peaks in the striatum by means of image analysis, striosome-matrix boundaries by [3H]naloxone binding, and primary somatosensory corticostriatal input clusters by injections of anterograde tracer into electrophysiologically identified sites in SI. Peak metabolic activity was primarily confined to the matrix compartment under each behavioral condition. These findings show that during relatively neutral behavioral conditions the balance of activity between the two compartments favors the matrix and suggest that this balance is present in the striatum as part of normal behavior and processing of afferent activity.

  13. Cyclical strain modulates metalloprotease and matrix gene expression in human tenocytes via activation of TGFβ.

    PubMed

    Jones, Eleanor R; Jones, Gavin C; Legerlotz, Kirsten; Riley, Graham P

    2013-12-01

    Tendinopathies are a range of diseases characterised by degeneration and chronic tendon pain and represent a significant cause of morbidity. Relatively little is known about the underlying mechanisms; however onset is often associated with physical activity. A number of molecular changes have been documented in tendinopathy such as a decrease in overall collagen content, increased extracellular matrix turnover and protease activity. Metalloproteinases are involved in the homeostasis of the extracellular matrix and expression is regulated by mechanical strain. The aims of this study were to determine the effects of strain upon matrix turnover by measuring metalloproteinase and matrix gene expression and to elucidate the mechanism of action. Primary Human Achilles tenocytes were seeded in type I rat tail collagen gels in a Flexcell™ tissue train system and subjected to 5% cyclic uniaxial strain at 1Hz for 48h. TGFβ1 and TGFβRI inhibitor were added to selected cultures. RNA was measured using qRT-PCR and TGFβ protein levels were determined using a cell based luciferase assay. We observed that mechanical strain regulated the mRNA levels of multiple protease and matrix genes anabolically, and this regulation mirrored that seen with TGFβ stimulation alone. We have also demonstrated that the inhibition of the TGFβ signalling pathway abrogated the strain induced changes in mRNA and that TGFβ activation, rather than gene expression, was increased with mechanical strain. We concluded that TGFβ activation plays an important role in mechanotransduction. Targeting this pathway may have its place in the treatment of tendinopathy.

  14. Matrix rigidity activates Wnt signaling through down-regulation of Dickkopf-1 protein.

    PubMed

    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

    2013-01-04

    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.

  15. 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

  16. The decellularized porcine heart valve matrix in tissue engineering: platelet adhesion and activation.

    PubMed

    Kasimir, Marie-Theres; Weigel, Guenter; Sharma, Jyotindra; Rieder, Erwin; Seebacher, Gernot; Wolner, Ernst; Simon, Paul

    2005-09-01

    An approach in tissue engineering of heart valves is the use of decellularized xenogeneic matrices to avoid immune response after implantation. The decellularization process must preserve the structural components of the extracellular matrix to provide a biomechanically stable scaffold. However, it is known that in vascular lesions platelet adhesion to extracellular matrix components occurs and platelet activation is induced. In the present study we examined the effects of a decellularized porcine heart valve matrix on thrombocyte activation and the influence of re-endothelialisation in vitro. Porcine pulmonary conduits were decellularized using Triton X-100, Na-deoxycholate and Igepal CA-630 followed by a ribonuclease digestion. Cryostat sections of decellularized heart valves with and without seeding with human umbilical vein endothelial cells (HUVEC) were incubated with platelet rich plasma. Samples were either stained with fluorescent antibodies for CD41 and PAC-I (recognizing the activated fibrinogen receptor) or fixed with glutaraldehyde. Thereafter, the samples were processed for laser scanning microscopy (LSM) or scanning electron microscopy (SEM). Examination by LSM showed numerous platelets with co-localized staining for CD41 and PAC-1 on the nonseeded decellularized heart valve matrix whereas after seeding with endothelial cells no platelet activation was detected. SEM revealed platelet adhesion and aggregate formation only on the surface of the non-seeded or partially denuded matrix specimens. We show in this study that the decellularized porcine matrix acts as a platelet-activating surface. Seeding with endothelial cells effectively abolishes the platelet adhesion and activation and therefore is necessary to eliminate thrombogenicity in tissue engineered heart valves.

  17. CMOS monolithic pixel sensors research and development at LBNL

    NASA Astrophysics Data System (ADS)

    Contarato, D.; Bussat, J.-M.; Denes, P.; Greiner, L.; Kim, T.; Stezelberger, T.; Wieman, H.; Battaglia, M.; Hooberman, B.; Tompkins, L.

    2007-12-01

    This paper summarizes the recent progress in the design and characterization of CMOS pixel sensors at LBNL. Results of lab tests, beam tests and radiation hardness tests carried out at LBNL on a test structure with pixels of various sizes are reported. The first results of the characterization of back-thinned CMOS pixel sensors are also reported, and future plans and activities are discussed.

  18. 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.

  19. Analysis of pixel circuits in CMOS image sensors

    NASA Astrophysics Data System (ADS)

    Mei, Zou; Chen, Nan; Yao, Li-bin

    2015-04-01

    CMOS image sensors (CIS) have lower power consumption, lower cost and smaller size than CCD image sensors. However, generally CCDs have higher performance than CIS mainly due to lower noise. The pixel circuit used in CIS is the first part of the signal processing circuit and connected to photodiode directly, so its performance will greatly affect the CIS or even the whole imaging system. To achieve high performance, CMOS image sensors need advanced pixel circuits. There are many pixel circuits used in CIS, such as passive pixel sensor (PPS), 3T and 4T active pixel sensor (APS), capacitive transimpedance amplifier (CTIA), and passive pixel sensor (PPS). At first, the main performance parameters of each pixel structure including the noise, injection efficiency, sensitivity, power consumption, and stability of bias voltage are analyzed. Through the theoretical analysis of those pixel circuits, it is concluded that CTIA pixel circuit has good noise performance, high injection efficiency, stable photodiode bias, and high sensitivity with small integrator capacitor. Furthermore, the APS and CTIA pixel circuits are simulated in a standard 0.18-μm CMOS process and using a n-well/p-sub photodiode by SPICE and the simulation result confirms the theoretical analysis result. It shows the possibility that CMOS image sensors can be extended to a wide range of applications requiring high performance.

  20. Pixelated gamma detector

    SciTech Connect

    Dolinsky, Sergei Ivanovich; Yanoff, Brian David; Guida, Renato; Ivan, Adrian

    2016-12-27

    A pixelated gamma detector includes a scintillator column assembly having scintillator crystals and optical transparent elements alternating along a longitudinal axis, a collimator assembly having longitudinal walls separated by collimator septum, the collimator septum spaced apart to form collimator channels, the scintillator column assembly positioned adjacent to the collimator assembly so that the respective ones of the scintillator crystal are positioned adjacent to respective ones of the collimator channels, the respective ones of the optical transparent element are positioned adjacent to respective ones of the collimator septum, and a first photosensor and a second photosensor, the first and the second photosensor each connected to an opposing end of the scintillator column assembly. A system and a method for inspecting and/or detecting defects in an interior of an object are also disclosed.

  1. Commissioning of the ATLAS pixel detector

    SciTech Connect

    ATLAS Collaboration; Golling, Tobias

    2008-09-01

    The ATLAS pixel detector is a high precision silicon tracking device located closest to the LHC interaction point. It belongs to the first generation of its kind in a hadron collider experiment. It will provide crucial pattern recognition information and will largely determine the ability of ATLAS to precisely track particle trajectories and find secondary vertices. It was the last detector to be installed in ATLAS in June 2007, has been fully connected and tested in-situ during spring and summer 2008, and is ready for the imminent LHC turn-on. The highlights of the past and future commissioning activities of the ATLAS pixel system are presented.

  2. Pixelation Effects in Weak Lensing

    NASA Technical Reports Server (NTRS)

    High, F. William; Rhodes, Jason; Massey, Richard; Ellis, Richard

    2007-01-01

    Weak gravitational lensing can be used to investigate both dark matter and dark energy but requires accurate measurements of the shapes of faint, distant galaxies. Such measurements are hindered by the finite resolution and pixel scale of digital cameras. We investigate the optimum choice of pixel scale for a space-based mission, using the engineering model and survey strategy of the proposed Supernova Acceleration Probe as a baseline. We do this by simulating realistic astronomical images containing a known input shear signal and then attempting to recover the signal using the Rhodes, Refregier, and Groth algorithm. We find that the quality of shear measurement is always improved by smaller pixels. However, in practice, telescopes are usually limited to a finite number of pixels and operational life span, so the total area of a survey increases with pixel size. We therefore fix the survey lifetime and the number of pixels in the focal plane while varying the pixel scale, thereby effectively varying the survey size. In a pure trade-off for image resolution versus survey area, we find that measurements of the matter power spectrum would have minimum statistical error with a pixel scale of 0.09' for a 0.14' FWHM point-spread function (PSF). The pixel scale could be increased to 0.16' if images dithered by exactly half-pixel offsets were always available. Some of our results do depend on our adopted shape measurement method and should be regarded as an upper limit: future pipelines may require smaller pixels to overcome systematic floors not yet accessible, and, in certain circumstances, measuring the shape of the PSF might be more difficult than those of galaxies. However, the relative trends in our analysis are robust, especially those of the surface density of resolved galaxies. Our approach thus provides a snapshot of potential in available technology, and a practical counterpart to analytic studies of pixelation, which necessarily assume an idealized shape

  3. Design methodology: edgeless 3D ASICs with complex in-pixel processing for pixel detectors

    SciTech Connect

    Fahim Farah, Fahim Farah; Deptuch, Grzegorz W.; Hoff, James R.; Mohseni, Hooman

    2015-08-28

    The design methodology for the development of 3D integrated edgeless pixel detectors with in-pixel processing using Electronic Design Automation (EDA) tools is presented. A large area 3 tier 3D detector with one sensor layer and two ASIC layers containing one analog and one digital tier, is built for x-ray photon time of arrival measurement and imaging. A full custom analog pixel is 65μm x 65μm. It is connected to a sensor pixel of the same size on one side, and on the other side it has approximately 40 connections to the digital pixel. A 32 x 32 edgeless array without any peripheral functional blocks constitutes a sub-chip. The sub-chip is an indivisible unit, which is further arranged in a 6 x 6 array to create the entire 1.248cm x 1.248cm ASIC. Each chip has 720 bump-bond I/O connections, on the back of the digital tier to the ceramic PCB. All the analog tier power and biasing is conveyed through the digital tier from the PCB. The assembly has no peripheral functional blocks, and hence the active area extends to the edge of the detector. This was achieved by using a few flavors of almost identical analog pixels (minimal variation in layout) to allow for peripheral biasing blocks to be placed within pixels. The 1024 pixels within a digital sub-chip array have a variety of full custom, semi-custom and automated timing driven functional blocks placed together. The methodology uses a modified mixed-mode on-top digital implementation flow to not only harness the tool efficiency for timing and floor-planning but also to maintain designer control over compact parasitically aware layout. The methodology uses the Cadence design platform, however it is not limited to this tool.

  4. Silicate-matrix active media for tunable solid-state lasers

    SciTech Connect

    Kuznetsova, Rimma T; Mayer, G V; Manekina, Yu A; Tel'minov, E N; Arabei, S M; Pavich, T A; Solovyov, Konstantin N

    2007-08-31

    The lasing characteristics of solid active media based on laser dyes (rhodamines, coumarin 2, paraterphenyl) doped into silicate bulk matrices and thin films of different compositions are studied upon optical excitation. The lasing efficiency, photostability, and spectral parameters of laser media are investigated as functions of the excitation wavelength and intensity. Variations in these parameters due to the interaction of organic luminophores with a silicate matrix and radiation are discussed. (active media. lasers)

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

    PubMed Central

    Jasin, H E

    1983-01-01

    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. Images PMID:6358260

  6. THE KEPLER PIXEL RESPONSE FUNCTION

    SciTech Connect

    Bryson, Stephen T.; Haas, Michael R.; Dotson, Jessie L.; Koch, David G.; Borucki, William J.; Tenenbaum, Peter; Jenkins, Jon M.; Chandrasekaran, Hema; Caldwell, Douglas A.; Klaus, Todd; Gilliland, Ronald L.

    2010-04-20

    Kepler seeks to detect sequences of transits of Earth-size exoplanets orbiting solar-like stars. Such transit signals are on the order of 100 ppm. The high photometric precision demanded by Kepler requires detailed knowledge of how the Kepler pixels respond to starlight during a nominal observation. This information is provided by the Kepler pixel response function (PRF), defined as the composite of Kepler's optical point-spread function, integrated spacecraft pointing jitter during a nominal cadence and other systematic effects. To provide sub-pixel resolution, the PRF is represented as a piecewise-continuous polynomial on a sub-pixel mesh. This continuous representation allows the prediction of a star's flux value on any pixel given the star's pixel position. The advantages and difficulties of this polynomial representation are discussed, including characterization of spatial variation in the PRF and the smoothing of discontinuities between sub-pixel polynomial patches. On-orbit super-resolution measurements of the PRF across the Kepler field of view are described. Two uses of the PRF are presented: the selection of pixels for each star that maximizes the photometric signal-to-noise ratio for that star, and PRF-fitted centroids which provide robust and accurate stellar positions on the CCD, primarily used for attitude and plate scale tracking. Good knowledge of the PRF has been a critical component for the successful collection of high-precision photometry by Kepler.

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

    PubMed

    Murakami, Kohei; Maeda, Shingo; Yonezawa, Tomohiro; Matsuki, Naoaki

    2016-07-01

    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.

  8. Drosophila SAF-B Links the Nuclear Matrix, Chromosomes, and Transcriptional Activity

    PubMed Central

    Alfonso-Parra, Catalina; Maggert, Keith A.

    2010-01-01

    Induction of gene expression is correlated with alterations in nuclear organization, including proximity to other active genes, to the nuclear cortex, and to cytologically distinct domains of the nucleus. Chromosomes are tethered to the insoluble nuclear scaffold/matrix through interaction with Scaffold/Matrix Attachment Region (SAR/MAR) binding proteins. Identification and characterization of proteins involved in establishing or maintaining chromosome-scaffold interactions is necessary to understand how the nucleus is organized and how dynamic changes in attachment are correlated with alterations in gene expression. We identified and characterized one such scaffold attachment factor, a Drosophila homolog of mammalian SAF-B. The large nuclei and chromosomes of Drosophila have allowed us to show that SAF-B inhabits distinct subnuclear compartments, forms weblike continua in nuclei of salivary glands, and interacts with discrete chromosomal loci in interphase nuclei. These interactions appear mediated either by DNA-protein interactions, or through RNA-protein interactions that can be altered during changes in gene expression programs. Extraction of soluble nuclear proteins and DNA leaves SAF-B intact, showing that this scaffold/matrix-attachment protein is a durable component of the nuclear matrix. Together, we have shown that SAF-B links the nuclear scaffold, chromosomes, and transcriptional activity. PMID:20422039

  9. Toll-like receptor 2 activation and serum amyloid A regulate smooth muscle cell extracellular matrix

    PubMed Central

    Bishop, Christopher A.; Best, Michael; Rich, Celeste B.; Stone, Phillip J.

    2017-01-01

    Smooth muscle cells contribute to extracellular matrix remodeling during atherogenesis. De-differentiated, synthetic smooth muscle cells are involved in processes of migration, proliferation and changes in expression of extracellular matrix components, all of which contribute to loss of homeostasis accompanying atherogenesis. Elevated levels of acute phase proteins, including serum amyloid A (SAA), are associated with an increased risk for atherosclerosis. Although infection with periodontal and respiratory pathogens via activation of inflammatory cell Toll-like receptor (TLR)2 has been linked to vascular disease, little is known about smooth muscle cell TLR2 in atherosclerosis. This study addresses the role of SAA and TLR2 activation on smooth muscle cell matrix gene expression and insoluble elastin accumulation. Cultured rat aortic smooth muscle cells were treated with SAA or TLR2 agonists and the effect on expression of matrix metallopeptidase 9 (MMP9) and tropoelastin studied. SAA up-regulated MMP9 expression. Tropoelastin is an MMP9 substrate and decreased tropoelastin levels in SAA-treated cells supported the concept of extracellular matrix remodeling. Interestingly, SAA-induced down-regulation of tropoelastin was not only evident at the protein level but at the level of gene transcription as well. Contributions of proteasomes, nuclear factor κ B and CCAAT/enhancer binding protein β on regulation of MMP9 vs. tropoleastin expression were revealed. Effects on Mmp9 and Eln mRNA expression persisted with long-term SAA treatment, resulting in decreased insoluble elastin accumulation. Interestingly, the SAA effects were TLR2-dependent and TLR2 activation by bacterial ligands also induced MMP9 expression and decreased tropoelastin expression. These data reveal a novel mechanism whereby SAA and/or infection induce changes in vascular elastin consistent with atherosclerosis. PMID:28257481

  10. PIXELS: Using field-based learning to investigate students' concepts of pixels and sense of scale

    NASA Astrophysics Data System (ADS)

    Pope, A.; Tinigin, L.; Petcovic, H. L.; Ormand, C. J.; LaDue, N.

    2015-12-01

    Empirical work over the past decade supports the notion that a high level of spatial thinking skill is critical to success in the geosciences. Spatial thinking incorporates a host of sub-skills such as mentally rotating an object, imagining the inside of a 3D object based on outside patterns, unfolding a landscape, and disembedding critical patterns from background noise. In this study, we focus on sense of scale, which refers to how an individual quantified space, and is thought to develop through kinesthetic experiences. Remote sensing data are increasingly being used for wide-reaching and high impact research. A sense of scale is critical to many areas of the geosciences, including understanding and interpreting remotely sensed imagery. In this exploratory study, students (N=17) attending the Juneau Icefield Research Program participated in a 3-hour exercise designed to study how a field-based activity might impact their sense of scale and their conceptions of pixels in remotely sensed imagery. Prior to the activity, students had an introductory remote sensing lecture and completed the Sense of Scale inventory. Students walked and/or skied the perimeter of several pixel types, including a 1 m square (representing a WorldView sensor's pixel), a 30 m square (a Landsat pixel) and a 500 m square (a MODIS pixel). The group took reflectance measurements using a field radiometer as they physically traced out the pixel. The exercise was repeated in two different areas, one with homogenous reflectance, and another with heterogeneous reflectance. After the exercise, students again completed the Sense of Scale instrument and a demographic survey. This presentation will share the effects and efficacy of the field-based intervention to teach remote sensing concepts and to investigate potential relationships between students' concepts of pixels and sense of scale.

  11. From Pixels to Planets

    NASA Technical Reports Server (NTRS)

    Brownston, Lee; Jenkins, Jon M.

    2015-01-01

    The Kepler Mission was launched in 2009 as NASAs first mission capable of finding Earth-size planets in the habitable zone of Sun-like stars. Its telescope consists of a 1.5-m primary mirror and a 0.95-m aperture. The 42 charge-coupled devices in its focal plane are read out every half hour, compressed, and then downlinked monthly. After four years, the second of four reaction wheels failed, ending the original mission. Back on earth, the Science Operations Center developed the Science Pipeline to analyze about 200,000 target stars in Keplers field of view, looking for evidence of periodic dimming suggesting that one or more planets had crossed the face of its host star. The Pipeline comprises several steps, from pixel-level calibration, through noise and artifact removal, to detection of transit-like signals and the construction of a suite of diagnostic tests to guard against false positives. The Kepler Science Pipeline consists of a pipeline infrastructure written in the Java programming language, which marshals data input to and output from MATLAB applications that are executed as external processes. The pipeline modules, which underwent continuous development and refinement even after data started arriving, employ several analytic techniques, many developed for the Kepler Project. Because of the large number of targets, the large amount of data per target and the complexity of the pipeline algorithms, the processing demands are daunting. Some pipeline modules require days to weeks to process all of their targets, even when run on NASA's 128-node Pleiades supercomputer. The software developers are still seeking ways to increase the throughput. To date, the Kepler project has discovered more than 4000 planetary candidates, of which more than 1000 have been independently confirmed or validated to be exoplanets. Funding for this mission is provided by NASAs Science Mission Directorate.

  12. Activated matrix metalloproteinase and disrupted myocardial collagen matrix in increased sympathetic activity following stimulation of dorsal medulla in the vagotomized feline model.

    PubMed

    Cheng, Ching-Chang; Tung, Kwong-Chung; Fu, Yun-Ching; Gong, Chi-Li; Chen, Ying-Tsung; Lin, Nai-Nu; Lin, James A; Chiu, Yung-Tsung

    2008-02-29

    Sympathetic hyperactivation in many kinds of neurocardiogenic injury can result in obvious heart failure. We generated a vagotomized feline model in which sympathetic hyperactivation was induced by electrical stimulation of dorsal medulla (ESDM) of brain stem to investigate the relationship between disruption of extracellular collagen matrix (ECM) and activation of matrix metalloproteinases (MMPs) in myocardium in the sympathetic hyperactivity. Mean blood pressure, heart rate and plasma norepinephrine were all significantly increased from baseline to a peak at 5 min after ESDM. Echocardiographic study showed significant left ventricular dilatation and hypokinesia (ejection fraction: from 87.7 +/- 6.3% to 39.4 +/- 7.8%) from baseline to 180 mm after ESDM. Histopathological finding revealed significant overstretching or spring-like disappearance and disruption of ECM. MMP-2 expression was significantly increased in left ventricular myocardium as compared to sham. These results suggest that ESDM-induced sympathetic hyperactivity causes the expression of MMP-2 that disrupts myocardial ECM, contributing to the development of cardiac dysfunction.

  13. 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.

  14. Matrix metalloproteinase expression and activity in human airway smooth muscle cells

    PubMed Central

    Elshaw, Shona R; Henderson, Neil; Knox, Alan J; Watson, Susan A; Buttle, David J; Johnson, Simon R

    2004-01-01

    Airway remodelling is a feature of chronic asthma comprising smooth muscle hypertrophy and deposition of extracellular matrix (ECM) proteins. Matrix metalloproteinases (MMPs) breakdown ECM, are involved in tissue remodelling and have been implicated in airway remodelling. Although mesenchymal cells are an important source of MMPs, little data are available on airway smooth muscle (ASM) derived MMPs. We therefore investigated MMP and tissue inhibitor of metalloproteinase (TIMP) production and activity in human ASM cells.MMPs and TIMPs were examined using quantitative real-time RT–PCR, Western blotting, zymography and a quench fluorescence (QF) assay of total MMP activity.The most abundant MMPs were pro-MMP-2, pro- MMP-3, active MMP-3 and MT1-MMP. TIMP-1 and TIMP-2 expression was low in cell lysates but high in conditioned medium. High TIMP secretion was confirmed by the ability of ASM-conditioned medium to inhibit recombinant MMP-2 in a QF assay. Thrombin increased MMP activity by activation of pro-MMP-2 independent of the conventional smooth muscle thrombin receptors PAR 1 and 4.In conclusion, ASM cells express pro-MMP-2, pro and active MMP-3, MMP-9 and MT1-MMP. Unstimulated cells secrete excess TIMP 1 and 2, preventing proteolytic activity. MMP-2 can be activated by thrombin which may contribute to airway remodelling. PMID:15265805

  15. Novel integrated CMOS pixel structures for vertex detectors

    SciTech Connect

    Kleinfelder, Stuart; Bieser, Fred; Chen, Yandong; Gareus, Robin; Matis, Howard S.; Oldenburg, Markus; Retiere, Fabrice; Ritter, Hans Georg; Wieman, Howard H.; Yamamoto, Eugene

    2003-10-29

    Novel CMOS active pixel structures for vertex detector applications have been designed and tested. The overriding goal of this work is to increase the signal to noise ratio of the sensors and readout circuits. A large-area native epitaxial silicon photogate was designed with the aim of increasing the charge collected per struck pixel and to reduce charge diffusion to neighboring pixels. The photogate then transfers the charge to a low capacitance readout node to maintain a high charge to voltage conversion gain. Two techniques for noise reduction are also presented. The first is a per-pixel kT/C noise reduction circuit that produces results similar to traditional correlated double sampling (CDS). It has the advantage of requiring only one read, as compared to two for CDS, and no external storage or subtraction is needed. The technique reduced input-referred temporal noise by a factor of 2.5, to 12.8 e{sup -}. Finally, a column-level active reset technique is explored that suppresses kT/C noise during pixel reset. In tests, noise was reduced by a factor of 7.6 times, to an estimated 5.1 e{sup -} input-referred noise. The technique also dramatically reduces fixed pattern (pedestal) noise, by up to a factor of 21 in our tests. The latter feature may possibly reduce pixel-by-pixel pedestal differences to levels low enough to permit sparse data scan without per-pixel offset corrections.

  16. Pixel telescope test in STAR at RHIC

    NASA Astrophysics Data System (ADS)

    Sun, Xiangming; Szelezniak, Michal; Greiner, Leo; Matis, Howard; Vu, Chinh; Stezelberger, Thorsten; Wieman, Howard

    2007-10-01

    The STAR experiment at RHIC is designing a new inner vertex detector called the Heavy Flavor Tracker (HFT). The HFT's innermost two layers is called the PIXEL detector which uses Monolithic Active Pixel Sensor technology (MAPS). To test the MAPS technology, we just constructed and tested a telescope. The telescope uses a stack of three MIMOSTAR2 chips, Each MIMOSTAR2 sensor, which was designed by IPHC, is an array of 132x128 pixels with a square pixel size of 30 μ. The readout of the telescope makes use of the ALICE DDL/SIU cards, which is compatible with the future STAR data acquisition system called DAQ1000. The telescope was first studied in a 1.2 GeV/c electron beam at LBNL's Advanced Light Source. Afterwards, the telescope was outside the STAR magnet, and then later inside it, 145 cm away from STAR's center. We will describe this first test of MAPS technology in a collider environment, and report on the occupancy, particle flux, and performance of the telescope.

  17. High Density, High Radiance $\\mu$ LED Matrix for Optogenetic Retinal Prostheses and Planar Neural Stimulation.

    PubMed

    Soltan, Ahmed; McGovern, Brian; Drakakis, Emmanuel; Neil, Mark; Maaskant, Pleun; Akhter, Mahbub; Lee, Jun Su; Degenaar, Patrick

    2017-04-01

    Optical neuron stimulation arrays are important for both in-vitro biology and retinal prosthetic biomedical applications. Hence, in this work, we present an 8100 pixel high radiance photonic stimulator. The chip module vertically combines custom made gallium nitride μ LEDs with a CMOS application specific integrated circuit. This is designed with active pixels to ensure random access and to allow continuous illumination of all required pixels. The μLEDs have been assembled on the chip using a solder ball flip-chip bonding technique which has allowed for reliable and repeatable manufacture. We have evaluated the performance of the matrix by measuring the different factors including the static, dynamic power consumption, the illumination, and the current consumption by each LED. We show that the power consumption is within a range suitable for portable use. Finally, the thermal behavior of the matrix is monitored and the matrix proved to be thermally stable.

  18. Activation of matrix metalloproteinase-2 from hepatic stellate cells requires interactions with hepatocytes.

    PubMed Central

    Théret, N.; Musso, O.; L'Helgoualc'h, A.; Clément, B.

    1997-01-01

    Activation of matrix metalloproteinase (MMP)-2, the 72-kd collagenase IV/gelatinase A, is involved in extracellular matrix remodeling. It has been suggested that a membrane-type MMP (MT-MMP-1) and the tissue inhibitor of metalloproteinase (TIMP)-2 are involved in MMP-2 processing, but the exact mechanism(s) of its activation remains unclear. We have investigated the role of cell-cell cooperation in the activation of pro-MMP-2 in the liver, using pure cultures and co-cultures of hepatocytes and hepatic stellate cells (HSCs). Northern blot analysis and in situ hybridization showed that, in both pure and co-cultures, HSCs, but not hepatocytes, expressed MMP-2, TIMP-2, and MT-MMP-1 mRNA. Zymography analyses revealed the latent form of MMP-2 in medium from 2-day-old pure HSC cultures with higher amounts in medium from hepatocyte/HSC co-cultures. When hepatocytes were added to 10-day-old HSC cultures, the activated form of MMP-2 was detected, concomitantly with the deposition of an abundant extracellular matrix. Incubation of plasma membrane-enriched fractions from hepatocytes with conditioned medium from pure HSC cultures generated the activated species of MMP-2 (62 and 59 kd). Activation of pro-MMP-2 by hepatocyte membranes was inhibited by EDTA, heat, and trypsin but not by serine proteinase inhibitors. These data show that the co-expression of TIMP-2, MMP-2, and MT-MMP-1 by HSCs does not lead to secretion of the activated form of MMP-2. Hepatocytes, which do not express MMP-2, TIMP-2, or MT-MMP-1, induce MMP-2 activation through a plasma membrane-dependent mechanism(s), thus suggesting that cell-cell interactions are involved in this process in vivo. Images Figure 1 Figure 2 Figure 3 PMID:9006321

  19. Neural conversion of ES cells by an inductive activity on human amniotic membrane matrix

    PubMed Central

    Ueno, Morio; Matsumura, Michiru; Watanabe, Kiichi; Nakamura, Takahiro; Osakada, Fumitaka; Takahashi, Masayo; Kawasaki, Hiroshi; Kinoshita, Shigeru; Sasai, Yoshiki

    2006-01-01

    Here we report a human-derived material with potent inductive activity that selectively converts ES cells into neural tissues. Both mouse and human ES cells efficiently differentiate into neural precursors when cultured on the matrix components of the human amniotic membrane in serum-free medium [amniotic membrane matrix-based ES cell differentiation (AMED)]. AMED-induced neural tissues have regional characteristics (brainstem) similar to those induced by coculture with mouse PA6 stromal cells [a common method called stromal cell-derived inducing activity (SDIA) culture]. Like the SDIA culture, the AMED system is applicable to the in vitro generation of various CNS tissues, including dopaminergic neurons, motor neurons, and retinal pigment epithelium. In contrast to the SDIA method, which uses animal cells, the AMED culture uses a noncellular inductive material derived from an easily available human tissue; therefore, AMED should provide a more suitable and versatile system for generating a variety of neural tissues for clinical applications. PMID:16766664

  20. Flexible transistor active matrix array with all screen-printed electrodes

    NASA Astrophysics Data System (ADS)

    Peng, Boyu; Lin, Jiawei; Chan, Paddy K. L.

    2013-09-01

    Flexible transistor active matrix array is fabricated on PEN substrate using all screen-printed gate, source and drain electrodes. Parylene-C and DNTT act as gate dielectric layer and semiconductor, respectively. The transistor possesses high mobility (0.33 cm2V-1 s-1), large on/off ratio (< 106) and low leakage current (~10 pA). Active matrix array consists of 10×10 transistors were demonstrated. Transistors exhibited average mobility of 0.29 cm2V-1s-1 and on/off ratio larger than 104 in array form. In the transistor array, we achieve 75μm channel length and a size of 2 mm × 2 mm for each element in the array which indicates the current screen-printing method has large potential in large-area circuits and display applications.

  1. Notch modulates VEGF action in endothelial cells by inducing Matrix Metalloprotease activity

    PubMed Central

    2011-01-01

    Background In the vasculature, Notch signaling functions as a downstream effecter of Vascular Endothelial Growth Factor (VEGF) signaling. VEGF regulates sprouting angiogenesis in part by inducing and activating matrix metalloproteases (MMPs). This study sought to determine if VEGF regulation of MMPs was mediated via Notch signaling and to determine how Notch regulation of MMPs influenced endothelial cell morphogenesis. Methods and Results We assessed the relationship between VEGF and Notch signaling in cultured human umbilical vein endothelial cells. Overexpression of VEGF-induced Notch4 and the Notch ligand, Dll4, activated Notch signaling, and altered endothelial cell morphology in a fashion similar to that induced by Notch activation. Expression of a secreted Notch antagonist (Notch1 decoy) suppressed VEGF-mediated activation of endothelial Notch signaling and endothelial morphogenesis. We demonstrate that Notch mediates VEGF-induced matrix metalloprotease activity via induction of MMP9 and MT1-MMP expression and activation of MMP2. Introduction of a MMP inhibitor blocked Notch-mediated endothelial morphogenesis. In mice, analysis of VEGF-induced dermal angiogenesis demonstrated that the Notch1 decoy reduced perivascular MMP9 expression. Conclusions Taken together, our data demonstrate that Notch signaling can act downstream of VEGF signaling to regulate endothelial cell morphogenesis via induction and activation of specific MMPs. In a murine model of VEGF-induced dermal angiogenesis, Notch inhibition led to reduced MMP9 expression. PMID:21349159

  2. 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.

  3. 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.

  4. A novel CMOS sensor with in-pixel auto-zeroed discrimination for charged particle tracking

    NASA Astrophysics Data System (ADS)

    Degerli, Y.; Guilloux, F.; Orsini, F.

    2014-05-01

    With the aim of developing fast and granular Monolithic Active Pixels Sensors (MAPS) as new charged particle tracking detectors for high energy physics experiments, a new rolling shutter binary pixel architecture concept (RSBPix) with in-pixel correlated double sampling, amplification and discrimination is presented. The discriminator features auto-zeroing in order to compensate process-related transistor mismatches. In order to validate the pixel, a first monolithic CMOS sensor prototype, including a pixel array of 96 × 64 pixels, has been designed and fabricated in the Tower-Jazz 0.18 μm CMOS Image Sensor (CIS) process. Results of laboratory tests are presented.

  5. Measurements with MÖNCH, a 25 μm pixel pitch hybrid pixel detector

    NASA Astrophysics Data System (ADS)

    Ramilli, M.; Bergamaschi, A.; Andrae, M.; Brückner, M.; Cartier, S.; Dinapoli, R.; Fröjdh, E.; Greiffenberg, D.; Hutwelker, T.; Lopez-Cuenca, C.; Mezza, D.; Mozzanica, A.; Ruat, M.; Redford, S.; Schmitt, B.; Shi, X.; Tinti, G.; Zhang, J.

    2017-01-01

    MÖNCH is a hybrid silicon pixel detector based on charge integration and with analog readout, featuring a pixel size of 25×25 μm2. The latest working prototype consists of an array of 400×400 identical pixels for a total active area of 1×1 cm2. Its design is optimized for the single photon regime. An exhaustive characterization of this large area prototype has been carried out in the past months, and it confirms an ENC in the order of 35 electrons RMS and a dynamic range of ~4×12 keV photons in high gain mode, which increases to ~100×12 keV photons with the lowest gain setting. The low noise levels of MÖNCH make it a suitable candidate for X-ray detection at energies around 1 keV and below. Imaging applications in particular can benefit significantly from the use of MÖNCH: due to its extremely small pixel pitch, the detector intrinsically offers excellent position resolution. Moreover, in low flux conditions, charge sharing between neighboring pixels allows the use of position interpolation algorithms which grant a resolution at the micrometer-level. Its energy reconstruction and imaging capabilities have been tested for the first time at a low energy beamline at PSI, with photon energies between 1.75 keV and 3.5 keV, and results will be shown.

  6. Local Pixel Bundles: Bringing the Pixels to the People

    NASA Astrophysics Data System (ADS)

    Anderson, Jay

    2014-12-01

    The automated galaxy-based alignment software package developed for the Frontier Fields program (hst2galign, see Anderson & Ogaz 2014 and http://www.stsci.edu/hst/campaigns/frontier-fields/) produces a direct mapping from the pixels of the flt frame of each science exposure into a common master frame. We can use these mappings to extract the flt-pixels in the vicinity of a source of interest and package them into a convenient "bundle". In addition to the pixels, this data bundle can also contain "meta" information that will allow users to transform positions from the flt pixels to the reference frame and vice-versa. Since the un-resampled pixels in the flt frames are the only true constraints we have on the astronomical scene, the ability to inter-relate these pixels will enable many high-precision studies, such as: point-source-fitting and deconvolution with accurate PSFs, easy exploration of different image-combining algorithms, and accurate faint-source finding and photometry. The data products introduced in this ISR are a very early attempt to provide the flt-level pixel constraints in a package that is accessible to more than the handful of experts in HST astrometry. The hope is that users in the community might begin using them and will provide feedback as to what information they might want to see in the bundles and what general analysis packages they might find useful. For that reason, this document is somewhat informally written, since I know that it will be modified and updated as the products and tools are optimized.

  7. Hybrid Pixel Detectors for gamma/X-ray imaging

    NASA Astrophysics Data System (ADS)

    Hatzistratis, D.; Theodoratos, G.; Zografos, V.; Kazas, I.; Loukas, D.; Lambropoulos, C. P.

    2015-09-01

    Hybrid pixel detectors are made by direct converting high-Z semi-insulating single crystalline material coupled to complementary-metal-oxide semiconductor (CMOS) readout electronics. They are attractive because direct conversion exterminates all the problems of spatial localization related to light diffusion, energy resolution, is far superior from the combination of scintillation crystals and photomultipliers and lithography can be used to pattern electrodes with very fine pitch. We are developing 2-D pixel CMOS ASICs, connect them to pixilated CdTe crystals with the flip chip and bump bonding method and characterize the hybrids. We have designed a series of circuits, whose latest member consists of a 50×25 pixel array with 400um pitch and an embedded controller. In every pixel a full spectroscopic channel with time tagging information has been implemented. The detectors are targeting Compton scatter imaging and they can be used for coded aperture imaging too. Hybridization using CMOS can overcome the limit put on pixel circuit complexity by the use of thin film transistors (TFT) in large flat panels. Hybrid active pixel sensors are used in dental imaging and other applications (e.g. industrial CT etc.). Thus X-ray imaging can benefit from the work done on dynamic range enhancement methods developed initially for visible and infrared CMOS pixel sensors. A 2-D CMOS ASIC with 100um pixel pitch to demonstrate the feasibility of such methods in the context of X-ray imaging has been designed.

  8. Ulex europaeus I lectin induces activation of matrix-metalloproteinase-2 in endothelial cells.

    PubMed

    Gomez, D E; Yoshiji, H; Kim, J C; Thorgeirsson, U P

    1995-11-02

    In this report, we show that the lectin Ulex europaeus agglutinin I (UEA I), which binds to alpha-linked fucose residues on the surface of endothelial cells, mediates activation of the 72-kDa matrix metalloproteinase-2 (MMP-2). A dose-dependent increase in the active 62-kDa form of MMP-2 was observed in conditioned medium from monkey aortic endothelial cells (MAEC) following incubation with concentrations of UEA I ranging from 2 to 100 micrograms/ml. The increase in the 62-kDa MMP-2 gelatinolytic activity was not reflected by a rise in MMP-2 gene expression. The UEA I-mediated activation of MMP-2 was blocked by L-fucose, which competes with UEA I for binding to alpha-fucose. These findings may suggest that a similar in vivo mechanism exists, whereby adhesive interactions between tumor cell lectins and endothelial cells can mediate MMP-2 activation.

  9. Functionalized mesoporous silica films as a matrix for anchoring electrochemically active guests.

    PubMed

    Fattakhova Rohlfing, Dina; Rathouský, Jirí; Rohlfing, Yven; Bartels, Oliver; Wark, Michael

    2005-11-22

    Mesoporous silica thin films were shown to be an appropriate matrix for immobilization of discrete electroactive moieties, yielding uniform transparent thin film electrodes with defined texture and enhanced electrochemical activity. The mesoporous silica films prepared on conducting FTO-coated glass substrate were postsynthetically functionalized. Alkoxysilanes were used as precursors for subsequent grafting via ionic or covalent bonds of representative electroactive species, such as polyoxometalate PMo12O(40)3-, hexacyanoferrate(III), and ferrocene. The electrochemically active concentration within the silica-based composite electrodes achieves 90, 260, and 60 micromol cm(-3) for polyoxometalate, hexacyanoferrate(III), and ferrocene, respectively. The amount of molecules involved in the charge-transfer sequence is proportional to the film thickness and comparable to the total amount of embedded guests. Thus, eventually the whole bulk volume of the modified silica films is electrochemically accessible. Immobilization in the chemically modified silica matrix alters the redox potential of the electroactive molecules. Electron exchange between the adjacent redox centers (electron hopping) is proposed as a possible charge propagation pathway through the insulating silica matrix, which is supported by the fact that the high charge uptake is observed also for the hybrid electrodes with the covalently anchored redox guests.

  10. Near Infrared Optical Proteolytic Beacons for In Vivo Imaging of Matrix Metalloproteinase Activity

    PubMed Central

    McIntyre, J. Oliver; Scherer, Randy L.; Matrisian, Lynn M.

    2010-01-01

    The exuberant expression of proteinases by tumor cells has long been associated with the breakdown of the extracellular matrix, tumor invasion, and metastasis to distant organs. There is both epidemiological and experimental data that support a causative role for proteinases of the matrix metalloproteinase (MMP) family in tumor progression. Optical imaging techniques provide an extraordinary opportunity for non-invasive “molecular imaging” of tumor-associated proteolytic activity. The application of optical proteolytic beacons for the detection of specific proteinase activities associated with tumors has several potential purposes: 1) Detection of small, early-stage tumors with increased sensitivity due to the catalytic nature of proteolytic activity, 2) Diagnosis and Prognosis to distinguished tumors that require particularly aggressive therapy or those that will not benefit from therapy, 3) Identification of tumors appropriate for specific anti-proteinase therapeutics and optimization of drug and dose based on determination of target modulation, and 4) as an indicator of efficacy of proteolytically-activated pro-drugs. This chapter describes the synthesis, characterization, and application of reagents that use visible and near infrared fluorescence resonance energy transfer (FRET) fluorophore pairs to detect and measure MMP-referable proteolytic activity in tumors in mouse models of cancer. PMID:20135290

  11. RNase L Suppresses Androgen Receptor Signaling, Cell Migration and Matrix Metalloproteinase Activity in Prostate Cancer Cells.

    PubMed

    Dayal, Shubham; Zhou, Jun; Manivannan, Praveen; Siddiqui, Mohammad Adnan; Ahmad, Omaima Farid; Clark, Matthew; Awadia, Sahezeel; Garcia-Mata, Rafael; Shemshedini, Lirim; Malathi, Krishnamurthy

    2017-03-01

    The interferon antiviral pathways and prostate cancer genetics converge on a regulated endoribonuclease, RNase L. Positional cloning and linkage studies mapped Hereditary Prostate Cancer 1 (HPC1) to RNASEL. To date, there is no correlation of viral infections with prostate cancer, suggesting that RNase L may play additional roles in tumor suppression. Here, we demonstrate a role of RNase L as a suppressor of androgen receptor (AR) signaling, cell migration and matrix metalloproteinase activity. Using RNase L mutants, we show that its nucleolytic activity is dispensable for both AR signaling and migration. The most prevalent HPC1-associated mutations in RNase L, R462Q and E265X, enhance AR signaling and cell migration. RNase L negatively regulates cell migration and attachment on various extracellular matrices. We demonstrate that RNase L knockdown cells promote increased cell surface expression of integrin β1 which activates Focal Adhesion Kinase-Sarcoma (FAK-Src) pathway and Ras-related C3 botulinum toxin substrate 1-guanosine triphosphatase (Rac1-GTPase) activity to increase cell migration. Activity of matrix metalloproteinase (MMP)-2 and -9 is significantly increased in cells where RNase L levels are ablated. We show that mutations in RNase L found in HPC patients may promote prostate cancer by increasing expression of AR-responsive genes and cell motility and identify novel roles of RNase L as a prostate cancer susceptibility gene.

  12. The inhibition of matrix metalloproteinase activity in chronic wounds by a polyacrylate superabsorber.

    PubMed

    Eming, Sabine; Smola, Hans; Hartmann, Berenike; Malchau, Gebhart; Wegner, Ronny; Krieg, Thomas; Smola-Hess, Sigrun

    2008-07-01

    Excessive matrix metalloproteinase (MMP) levels have been observed in wound fluid of impaired healing wounds. This is thought to interfere with granulation tissue formation as newly formed extracellular matrix and cytokines are degraded and the wound becomes deadlocked, unable to progress to the next healing stages. In the cleansing phase, associated with high MMP activity levels, hydroactive wound dressings containing polyacrylate superabsorber particles are particularly effective. We tested whether these particles can block MMP activity in wound fluid obtained from chronic venous leg ulcers. Polyacrylate superabsorber particles inhibited MMP activity by more than 87% in a fluorogenic peptide substrate assay. Further analysis revealed two underlying molecular mechanisms. First, experiments showed direct binding of MMPs to the particles. Secondly, polyacrylate superabsorber particles can bind Ca2+ and Zn2+ ions competing with MMPs for divalent ions required for enzymatic activity. Furthermore, we provide the first evidence in vivo that MMPs bind effectively to polyacrylate superabsorber particles within the hostile environment of chronic wounds. We conclude that polyacrylate superabsorber particles can rescue the highly proteolytic microenvironment of non-healing wounds from MMP activity so that more conductive conditions allow healing to proceed.

  13. RNase L Suppresses Androgen Receptor Signaling, Cell Migration and Matrix Metalloproteinase Activity in Prostate Cancer Cells

    PubMed Central

    Dayal, Shubham; Zhou, Jun; Manivannan, Praveen; Siddiqui, Mohammad Adnan; Ahmad, Omaima Farid; Clark, Matthew; Awadia, Sahezeel; Garcia-Mata, Rafael; Shemshedini, Lirim; Malathi, Krishnamurthy

    2017-01-01

    The interferon antiviral pathways and prostate cancer genetics converge on a regulated endoribonuclease, RNase L. Positional cloning and linkage studies mapped Hereditary Prostate Cancer 1 (HPC1) to RNASEL. To date, there is no correlation of viral infections with prostate cancer, suggesting that RNase L may play additional roles in tumor suppression. Here, we demonstrate a role of RNase L as a suppressor of androgen receptor (AR) signaling, cell migration and matrix metalloproteinase activity. Using RNase L mutants, we show that its nucleolytic activity is dispensable for both AR signaling and migration. The most prevalent HPC1-associated mutations in RNase L, R462Q and E265X, enhance AR signaling and cell migration. RNase L negatively regulates cell migration and attachment on various extracellular matrices. We demonstrate that RNase L knockdown cells promote increased cell surface expression of integrin β1 which activates Focal Adhesion Kinase-Sarcoma (FAK-Src) pathway and Ras-related C3 botulinum toxin substrate 1-guanosine triphosphatase (Rac1-GTPase) activity to increase cell migration. Activity of matrix metalloproteinase (MMP)-2 and -9 is significantly increased in cells where RNase L levels are ablated. We show that mutations in RNase L found in HPC patients may promote prostate cancer by increasing expression of AR-responsive genes and cell motility and identify novel roles of RNase L as a prostate cancer susceptibility gene. PMID:28257035

  14. New matrix polymers for photo-activated resin composites using di-alpha-fluoroacrylic acid derivatives.

    PubMed

    Kurata, Shigeaki; Yamazaki, Noboru

    2008-07-01

    A novel matrix resin for photo-activated resin composites was developed using alpha-fluoroacrylic acid derivatives. To render resin composites with improved mechanical properties, silica fillers were also used. It was found that the newly developed fluorine-substituted monomer was polymerized quite easily not only by free radical chemical initiators, but also by photoirradiation using free radical photoinitiator system. In particular, the photopolymerization rate of the novel monomer was more than two times faster than that of corresponding methacrylate-based monomer. Composite based on the newly developed matrix resin had higher micro-Vickers hardness and compressive strength values than the methacrylate-based composite, and that it contained only trace residual monomers compared with the methacrylate-based material. The high polymerization conversion of the fluorine-substituted monomer could be attributed to the polar effect or the small steric hindrance of fluorine at the alpha-position.

  15. Metamaterial-based single pixel imaging system (Presentation Recording)

    NASA Astrophysics Data System (ADS)

    Padilla, Willie; Watts, Claire M.; Nadell, Christian; Montoya, John A.; Krishna, Sanjay

    2015-09-01

    Single pixel cameras are useful imaging devices where it is difficult or infeasible to fashion focal plan arrays. For example in the Far Infrared (FIR) it is difficult to perform imaging by conventional detector arrays, owing to the cost and size of such an array. The typical single pixel camera uses a spatial light modulator (SLM) - placed in the conjugate image plane - and is used to sample various portions of the image. The spatially modulated light emerging from the SLM is then sent to a single detector where the light is condensed with suitable optics for detection. Conventional SLMs are either based on liquid crystals or digital mirror devices. As such these devices are limited in modulation speeds of order 30 kHz. Further there is little control over the type of light that is modulated. We present metamaterial based spatial light modulators which provide the ability to digitally encode images - with various measurement matrix coefficients - thus permitting high speed and fidelity imaging capability. In particular we use the Hadamard matrix and related S-matrix to encode images for single pixel imaging. Metamaterials thus permit imaging in regimes of the electromagnetic spectrum where conventional SLMs are not available. Additionally, metamaterials offer several salient features that are not available with commercial SLMs. For example, metamaterials may be used to enable hyperspectral, polarimetric, and phase sensitive imaging. We present the theory and experimental results of single pixel imaging with digital metamaterials in the far infrared and highlight the future of this exciting field.

  16. Synthesis of hydroxypyrone- and hydroxythiopyrone-based matrix metalloproteinase inhibitors: Developing a structure–activity relationship

    PubMed Central

    Yan, Yi-Long; Miller, Melissa T.; Cao, Yuchen; Cohen, Seth M.

    2010-01-01

    The zinc(II)-dependent matrix metalloproteinases (MMPs) are associated with a variety of diseases. Development of inhibitors to modulate MMP activity has been an active area of investigation for therapeutic development. Hydroxypyrones and hydroxythiopyrones are alternative zinc-binding groups (ZBGs) that, when combined with peptidomimetic backbones, comprise a novel class of MMP inhibitors (MMPi). In this report, a series of hydroxypyrone- and hydroxythiopyrone-based MMPi with aryl backbones at the 2-, 5-, and 6-positions of the hydroxypyrone ring have been synthesized. Synthetic routes for developing inhibitors with substituents at two of these positions (so-called double-handed inhibitors) are also explored. The MMP inhibition profiles and structure–activity relationship of synthesized hydroxypyrones and hydroxythiopyrones have been analyzed. The results here show that the ZBG, the position of the backbone on the ZBG, and the nature of the linker between the ZBG and backbone are critical for MMPi activities. PMID:19261472

  17. AMPK activity regulates trafficking of mitochondria to the leading edge during cell migration and matrix invasion

    PubMed Central

    Cunniff, Brian; McKenzie, Andrew J.; Heintz, Nicholas H.; Howe, Alan K.

    2016-01-01

    Cell migration is a complex behavior involving many energy-expensive biochemical events that iteratively alter cell shape and location. Mitochondria, the principal producers of cellular ATP, are dynamic organelles that fuse, divide, and relocate to respond to cellular metabolic demands. Using ovarian cancer cells as a model, we show that mitochondria actively infiltrate leading edge lamellipodia, thereby increasing local mitochondrial mass and relative ATP concentration and supporting a localized reversal of the Warburg shift toward aerobic glycolysis. This correlates with increased pseudopodial activity of the AMP-activated protein kinase (AMPK), a critically important cellular energy sensor and metabolic regulator. Furthermore, localized pharmacological activation of AMPK increases leading edge mitochondrial flux, ATP content, and cytoskeletal dynamics, whereas optogenetic inhibition of AMPK halts mitochondrial trafficking during both migration and the invasion of three-dimensional extracellular matrix. These observations indicate that AMPK couples local energy demands to subcellular targeting of mitochondria during cell migration and invasion. PMID:27385336

  18. Heart failure alters matrix metalloproteinase gene expression and activity in rat skeletal muscle.

    PubMed

    Carvalho, Robson Francisco; Dariolli, Rafael; Justulin Junior, Luis Antonio; Sugizaki, Mário Mateus; Politi Okoshi, Marina; Cicogna, Antonio Carlos; Felisbino, Sérgio Luis; Dal Pai-Silva, Maeli

    2006-12-01

    Heart failure is associated with a skeletal muscle myopathy with cellular and extracellular alterations. The hypothesis of this investigation is that extracellular changes may be associated with enhanced mRNA expression and activity of matrix metalloproteinases (MMP). We examined MMP mRNA expression and MMP activity in Soleus (SOL), extensor digitorum longus (EDL), and diaphragm (DIA) muscles of young Wistar rat with monocrotaline-induced heart failure. Rats injected with saline served as age-matched controls. MMP2 and MMP9 mRNA contents were determined by RT-PCR and MMP activity by electrophoresis in gelatin-containing polyacrylamide gels in the presence of SDS under non-reducing conditions. Heart failure increased MMP9 mRNA expression and activity in SOL, EDL and DIA and MMP2 mRNA expression in DIA. These results suggest that MMP changes may contribute to the skeletal muscle myopathy during heart failure.

  19. Short-term disruption in regional left ventricular electrical conduction patterns increases interstitial matrix metalloproteinase activity

    PubMed Central

    Zavadzkas, Juozas A.; Rivers, William T.; McLean, Julie E.; Chang, Eileen I.; Bouges, Shenikqua; Matthews, Robert G.; Koval, Christine N.; Stroud, Robert E.; Spinale, Francis G.

    2010-01-01

    Increased matrix metalloproteinase (MMP) abundance occurs with adverse left ventricular (LV) remodeling in a number of cardiac disease states, including those induced by long-standing arrhythmias. However, whether regionally contained aberrant electrical activation of the LV, with consequent dyskinesia, alters interstitial MMP activation remained unknown. Electrical activation of the LV of pigs (n = 10, 30–35 kg) was achieved by pacing (150 beats/min) at left atrial and LV sites such that normal atrioventricular activation (60 min) was followed by regional early LV activation for 60 min within 1.5 cm of the paced site and restoration of normal atrioventricular pacing for 120 min. Regional shortening (piezoelectric crystals) and interstitial MMP activity (microdialysis with MMP fluorogenic substrate) at the LV pacing site and a remote LV site were monitored at 30-min intervals. During aberrant electrical stimulation, interstitial MMP activity at the paced site was increased (122 ± 4%) compared with the remote region (100%, P < 0.05). Restoration of atrioventricular pacing after the 60-min period of aberrant electrical activation normalized segmental shortening (8.5 ± 0.4%), but MMP activity remained elevated (121 ± 6%, P < 0.05). This study demonstrates that despite the restoration of mechanical function, disturbances in electrical conduction, in and of itself, can cause acute increases in regional in vivo MMP activation and, therefore, contribute to myocardial remodeling. PMID:20472759

  20. Short-term disruption in regional left ventricular electrical conduction patterns increases interstitial matrix metalloproteinase activity.

    PubMed

    Mukherjee, Rupak; Zavadzkas, Juozas A; Rivers, William T; McLean, Julie E; Chang, Eileen I; Bouges, Shenikqua; Matthews, Robert G; Koval, Christine N; Stroud, Robert E; Spinale, Francis G

    2010-07-01

    Increased matrix metalloproteinase (MMP) abundance occurs with adverse left ventricular (LV) remodeling in a number of cardiac disease states, including those induced by long-standing arrhythmias. However, whether regionally contained aberrant electrical activation of the LV, with consequent dyskinesia, alters interstitial MMP activation remained unknown. Electrical activation of the LV of pigs (n = 10, 30-35 kg) was achieved by pacing (150 beats/min) at left atrial and LV sites such that normal atrioventricular activation (60 min) was followed by regional early LV activation for 60 min within 1.5 cm of the paced site and restoration of normal atrioventricular pacing for 120 min. Regional shortening (piezoelectric crystals) and interstitial MMP activity (microdialysis with MMP fluorogenic substrate) at the LV pacing site and a remote LV site were monitored at 30-min intervals. During aberrant electrical stimulation, interstitial MMP activity at the paced site was increased (122 +/- 4%) compared with the remote region (100%, P < 0.05). Restoration of atrioventricular pacing after the 60-min period of aberrant electrical activation normalized segmental shortening (8.5 +/- 0.4%), but MMP activity remained elevated (121 +/- 6%, P < 0.05). This study demonstrates that despite the restoration of mechanical function, disturbances in electrical conduction, in and of itself, can cause acute increases in regional in vivo MMP activation and, therefore, contribute to myocardial remodeling.

  1. 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.

  2. Design of a 3D-IC multi-resolution digital pixel sensor

    NASA Astrophysics Data System (ADS)

    Brochard, N.; Nebhen, J.; Dubois, J.; Ginhac, D.

    2016-04-01

    This paper presents a digital pixel sensor (DPS) integrating a sigma-delta analog-to-digital converter (ADC) at pixel level. The digital pixel includes a photodiode, a delta-sigma modulation and a digital decimation filter. It features adaptive dynamic range and multiple resolutions (up to 10-bit) with a high linearity. A specific row decoder and column decoder are also designed to permit to read a specific pixel chosen in the matrix and its neighborhood of 4 x 4. Finally, a complete design with the CMOS 130 nm 3D-IC FaStack Tezzaron technology is also described, revealing a high fill-factor of about 80%.

  3. Active metal-matrix composites with embedded smart materials by ultrasonic additive manufacturing

    NASA Astrophysics Data System (ADS)

    Hahnlen, Ryan; Dapino, Marcelo J.

    2010-04-01

    This paper presents the development of active aluminum-matrix composites manufactured by Ultrasonic Additive Manufacturing (UAM), an emerging rapid prototyping process based on ultrasonic metal welding. Composites created through this process experience temperatures as low as 25 °C during fabrication, in contrast to current metal-matrix fabrication processes which require temperatures of 500 °C and above. UAM thus provides unprecedented opportunities to develop adaptive structures with seamlessly embedded smart materials and electronic components without degrading the properties that make these materials and components attractive. This research focuses on developing UAM composites with aluminum matrices and embedded shape memory NiTi, magnetostrictive Galfenol, and electroactive PVDF phases. The research on these composites will focus on: (i) electrical insulation between NiTi and Al phases for strain sensors, investigation and modeling of NiTi-Al composites as tunable stiffness materials and thermally invariant structures based on the shape memory effect; (ii) process development and composite testing for Galfenol-Al composites; and (iii) development of PVDF-Al composites for embedded sensing applications. We demonstrate a method to electrically insulate embedded materials from the UAM matrix, the ability create composites containing up to 22.3% NiTi, and their resulting dimensional stability and thermal actuation characteristics. Also demonstrated is Galfenol-Al composite magnetic actuation of up to 54 μ(see manuscript), and creation of a PVDF-Al composite sensor.

  4. Indirect flat-panel detector with avalanche gain: Fundamental feasibility investigation for SHARP-AMFPI (scintillator HARP active matrix flat panel imager)

    SciTech Connect

    Zhao Wei; Li Dan; Reznik, Alla; Lui, B.J.M.; Hunt, D.C.; Rowlands, J.A.; Ohkawa, Yuji; Tanioka, Kenkichi

    2005-09-15

    An indirect flat-panel imager (FPI) with avalanche gain is being investigated for low-dose x-ray imaging. It is made by optically coupling a structured x-ray scintillator CsI(Tl) to an amorphous selenium (a-Se) avalanche photoconductor called HARP (high-gain avalanche rushing photoconductor). The final electronic image is read out using an active matrix array of thin film transistors (TFT). We call the proposed detector SHARP-AMFPI (scintillator HARP active matrix flat panel imager). The advantage of the SHARP-AMFPI is its programmable gain, which can be turned on during low dose fluoroscopy to overcome electronic noise, and turned off during high dose radiography to avoid pixel saturation. The purpose of this paper is to investigate the important design considerations for SHARP-AMFPI such as avalanche gain, which depends on both the thickness d{sub Se} and the applied electric field E{sub Se} of the HARP layer. To determine the optimal design parameter and operational conditions for HARP, we measured the E{sub Se} dependence of both avalanche gain and optical quantum efficiency of an 8 {mu}m HARP layer. The results were used in a physical model of HARP as well as a linear cascaded model of the FPI to determine the following x-ray imaging properties in both the avalanche and nonavalanche modes as a function of E{sub Se}: (1) total gain (which is the product of avalanche gain and optical quantum efficiency); (2) linearity; (3) dynamic range; (4) gain nonuniformity resulting from thickness nonuniformity; and (5) effects of direct x-ray interaction in HARP. Our results showed that a HARP layer thickness of 8 {mu}m can provide adequate avalanche gain and sufficient dynamic range for x-ray imaging applications to permit quantum limited operation over the range of exposures needed for radiography and fluoroscopy.

  5. Indirect flat-panel detector with avalanche gain: fundamental feasibility investigation for SHARP-AMFPI (scintillator HARP active matrix flat panel imager).

    PubMed

    Zhao, Wei; Li, Dan; Reznik, Alla; Lui, B J M; Hunt, D C; Rowlands, J A; Ohkawa, Yuji; Tanioka, Kenkichi

    2005-09-01

    An indirect flat-panel imager (FPI) with avalanche gain is being investigated for low-dose x-ray imaging. It is made by optically coupling a structured x-ray scintillator CsI(Tl) to an amorphous selenium (a-Se) avalanche photoconductor called HARP (high-gain avalanche rushing photoconductor). The final electronic image is read out using an active matrix array of thin film transistors (TFT). We call the proposed detector SHARP-AMFPI (scintillator HARP active matrix flat panel imager). The advantage of the SHARP-AMFPI is its programmable gain, which can be turned on during low dose fluoroscopy to overcome electronic noise, and turned off during high dose radiography to avoid pixel saturation. The purpose of this paper is to investigate the important design considerations for SHARP-AMFPI such as avalanche gain, which depends on both the thickness d(Se) and the applied electric field E(Se) of the HARP layer. To determine the optimal design parameter and operational conditions for HARP, we measured the E(Se) dependence of both avalanche gain and optical quantum efficiency of an 8 microm HARP layer. The results were used in a physical model of HARP as well as a linear cascaded model of the FPI to determine the following x-ray imaging properties in both the avalanche and nonavalanche modes as a function of E(Se): (1) total gain (which is the product of avalanche gain and optical quantum efficiency); (2) linearity; (3) dynamic range; (4) gain nonuniformity resulting from thickness nonuniformity; and (5) effects of direct x-ray interaction in HARP. Our results showed that a HARP layer thickness of 8 microm can provide adequate avalanche gain and sufficient dynamic range for x-ray imaging applications to permit quantum limited operation over the range of exposures needed for radiography and fluoroscopy.

  6. Noncolorimetric measurement of cell activity in three-dimensional histoculture using the tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide: the pixel image analysis of formazan crystals.

    PubMed

    Colangelo, D; Guo, H Y; Connors, K M; Silvestro, L; Hoffman, R M

    1992-08-15

    We describe a novel system for measuring the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction in three-dimensional histoculture which is no longer dependent on colorimetric determination of extracted formazan, but rather is based on a pixel image analysis of formazan crystals, and which allows intratumor heterogeneity to be taken into account. The MTT test is based on the enzymatic reduction of the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-dipheniltetrazolium bromide to formazan crystals by living, metabolically active cells, but not in dead cells. The reaction was carried out in situ in six-well plates on gel-supported histocultured human tumors. After a 24-h incubation with different drugs the tumors were incubated with a solution of MTT. Frozen sections of the tumor pieces were made and the slides were then stained with a propidium iodide solution, whose fluorescence is proportional to the number of cells present. We demonstrate here that the formazan crystals, formed by MTT reduction, reflect polarized light and that this can be quantified by using an image analysis system based on bright-pixel quantitation directly on a frozen section of the original tissue. Combined with the use of the fluorescent dye propidium iodide, also measured by pixel analysis, we can express a ratio between the total amount of MTT reduction and the total number of cells present in the specimen that expresses the effect of drugs on the histocultured tumors. Since histology is well maintained in histoculture it is possible to take into account the heterogeneity present in the tumor with regard to drug response.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Inhibition of matrix metalloproteinase activity in human dentin via novel antibacterial monomer

    PubMed Central

    Li, Fang; Majd, Hessam; Weir, Michael D.; Arola, Dwayne D.; Xu, Hockin H.K.

    2015-01-01

    Objectives Dentin-composite bond failure is caused by factors including hybrid layer degradation, which in turn can be caused by hydrolysis and enzymatic degradation of the exposed collagen in the dentin. The objectives of this study were to investigate a new antibacterial monomer (dimethylaminododecyl methacrylate, DMADDM) as an inhibitor for matrix metalloproteinases (MMPs), and to determine the effects of DMADDM on both soluble recombinant human MMPs (rhMMPs) and dentin matrix-bound endogenous MMPs. Methods Inhibitory effects of DMADDM at six mass% (0.1% to 10%) on soluble rhMMP-8 and rhMMP-9 were measured using a colorimetic assay. Matrix-bound endogenous MMP activity was evaluated in demineralized human dentin. Dentin beams were divided into four groups (n = 10) and incubated in calcium- and zinc-containing media (control medium); or control medium + 0.2% chlorhexidine (CHX); 5% 12-methacryloyloxydodecylpyridinium bromide (MDPB); or 5% DMADDM. Dissolution of dentin collagen peptides was evaluated by mechanical testing in three-point flexure, loss of dentin mass, and a hydroxyproline assay. Results Use of 0.1% to 10% DMADDM exhibited a strong concentration-dependent anti-MMP effect, reaching 90% of inhibition on rhMMP-8 and rhMMP-9 at 5% DMADDM concentration. Dentin beams in medium with 5% DMADDM showed 34% decrease in elastic modulus (vs. 73% decrease for control), 3% loss of dry dentin mass (vs. 28% loss for control), and significantly less solubilized hydroxyproline when compared with control (p < 0.05). Significance The new antibacterial monomer DMADDM was effective in inhibiting both soluble rhMMPs and matrix-bound human dentin MMPs. These results, together with previous studies showing that adhesives containing DMADDM inhibited biofilms without compromising dentin bond strength, suggest that DMADDM is promising for use in adhesives to prevent collagen degradation in hybrid layer and protect the resin-dentin bond. PMID:25595564

  8. Status and Construction of the Belle II DEPFET pixel system

    NASA Astrophysics Data System (ADS)

    Lütticke, Florian

    2014-06-01

    DEpleted P-channel Field Effect Transistor (DEPFET) active pixel detectors combine detection with a first amplification stage in a fully depleted detector, resulting in an superb signal-to-noise ratio even for thin sensors. Two layers of thin (75 micron) silicon DEPFET pixels will be used as the innermost vertex system, very close to the beam pipe in the Belle II detector at the SuperKEKB facility. The status of the 8 million DEPFET pixels detector, latest developments and current system tests will be discussed.

  9. PIASxbeta is a key regulator of osterix transcriptional activity and matrix mineralization in osteoblasts.

    PubMed

    Ali, Md Moksed; Yoshizawa, Tatsuya; Ishibashi, Osamu; Matsuda, Akio; Ikegame, Mika; Shimomura, Junko; Mera, Hisashi; Nakashima, Kazuhisa; Kawashima, Hiroyuki

    2007-08-01

    We recently reported that tensile stress induces osteoblast differentiation and osteogenesis in the mouse calvarial suture in vitro. Using this experimental system, we identified PIASxbeta, a splice isoform of Pias2, as one of the genes most highly upregulated by tensile stress. Further study using cell culture revealed that this upregulation was transient and was accompanied by upregulation of other differentiation markers, including osterix, whereas expression of Runx2 was unaffected. Runx2 and osterix are the two master proteins controlling osteoblast differentiation, with Runx2 being upstream of osterix. Targeted knockdown of PIASxbeta by small interfering RNA (siRNA) markedly suppressed osteoblastic differentiation and matrix mineralization, whereas transient overexpression of PIASxbeta caused the exact opposite effects. Regardless of PIASxbeta expression level, Runx2 expression remained constant. Reporter assays demonstrated that osterix enhanced its own promoter activity, which was further stimulated by PIASxbeta but not by its sumoylation-defective mutant. NFATc1 and NFATc3 additionally increased osterix transcriptional activity when co-transfected with PIASxbeta. Because osterix has no consensus motif for sumoylation, other proteins are probably involved in the PIASxbeta-mediated activation and NFAT proteins may be among such targets. This study provides the first line of evidence that PIASxbeta is indispensable for osteoblast differentiation and matrix mineralization, and that this signaling molecule is located between Runx2 and osterix.

  10. The dynamic interaction between matrix metalloproteinase activity and adverse myocardial remodeling.

    PubMed

    Janicki, Joseph S; Brower, Gregory L; Gardner, Jason D; Chancey, Amanda L; Stewart, James A

    2004-01-01

    The process of cardiac remodeling in response to cardiac injury and/or persistent elevations in wall stress generally relates to the progressive changes that occur in ventricular chamber dimensions and the various components of the myocardium, in particular the cardiomyocytes and the extracellular matrix. Volume overload, pressure overload or myocardial injury produces a sustained abnormal elevation in myocardial wall stress which initiates cardiac remodeling that frequently results in ventricular decompensation and heart failure. Regardless of the inciting cause, there appear to be three distinct phases to this process. In the initial phase, fibrillar collagen is partially degraded secondary to increased matrix metalloproteinase (MMP) activity. Following this, there is a chronic compensatory phase during which MMP activity and collagen concentration return to normal while cardiomyocyte size continues to progressively increase. The final phase is attained once the compensatory hypertrophic mechanisms are exhausted and is characterized by elevated MMP activity, marked ventricular dilatation and prominent fibrosis. Details of this progressive, dynamic remodeling process and its effect on ventricular function during chronic volume overload, chronic pressure overload and following myocardial infarction will be the focus of this article.

  11. Proteolytic degradation of intestinal mucosal extracellular matrix after lamina propria T cell activation.

    PubMed Central

    Pender, S L; Lionetti, P; Murch, S H; Wathan, N; MacDonald, T T

    1996-01-01

    BACKGROUND: Proteoglycans, consisting of glycosaminoglycan (GAG) side chains covalently linked to a protein core, are a major component of the extracellular matrix of the intestinal lamina propria. AIMS: This study investigated the effects of lamina propria T cell activation on the proteoglycan component of the matrix. METHODS: The high degree of sulphation of GAGs means that they are polyanionic and thus can be visualised in tissue sections by means of colloidal-gold labelled cationic probes. RESULTS: In human fetal small intestine there is a dense meshwork of anionic residues in the lamina propria and basement membrane. When explants of human fetal small intestine are cultured ex vivo, and resident lamina propria T cells are activated with pokeweed mitogen, mucosal destruction occurs within three days. This is associated with the rapid loss of anionic sites from the lamina propria. Dermatan sulphate proteoglycan is lost from the tissue and is present at increased concentrations in the organ culture supernatants, indicating that T cell activation has led to solubilisation of lamina propria proteoglycans. Tissue destruction and loss of anionic residues are inhibited in a dose dependent fashion by dexamethasone, and by the protease inhibitor, alpha 2 macroglobulin. CONCLUSIONS: Proteolytic degradation of the lamina propria may therefore be a mechanism by which T cell hypersensitivity injures the intestinal mucosa. Images Figure 1 Figure 4 Figure 5 PMID:8977345

  12. Activity of matrix metalloproteinase-2 (MMP-2) in canine oronasal tumors.

    PubMed

    Nakaichi, Munekazu; Yunuki, Toshi; Okuda, Masaru; Une, Satoshi; Taura, Yasuho

    2007-04-01

    Activity of matrix metalloprotease-2 (MMP-2) and the expression of its related molecules were examined in spontaneous canine oronasal tumors. Tissue samples from melanoma and squamous cell carcinoma possessed higher MMP-2 activity, as shown in gelatin zymography, in comparison with acanthomatous epulis and nasal adenocarcinoma. Regional lymph node invasion and distant metastases were more frequently observed in the MMP-2 positive cases. There were no significant differences by RT-PCR examination in the expression of the genes encoding MMP-2, MT1-MMP and TIMP-2 among the tumor histological types. However, the MMP-2/TIMP-2 ratio showed a significantly higher level of the genes in the malignant oral melanoma and squamous cell carcinoma. The MMP-2/TIMP-2 ratio was also positively correlated with MMP-2 activity in gelatin zymography. These results indicate that the MMP-2/TIMP-2 ratio may be of value in evaluating the prognosis in canine oronasal cavity tumors.

  13. 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

  14. Increased Serum Activity of Matrix Metalloproteinase-9 in Patients with Acute Variceal Bleeding

    PubMed Central

    Kwon, Oh Sang; Jung, Hyuk Sang; Bae, Kyung Sook; Jung, Young Kul; Kim, Yeon Suk; Choi, Duck Joo; Kim, Yun Soo

    2012-01-01

    Background/Aims Matrix metalloproteinases (MMP)-2 and -9 can degrade essential components of vascular integrity. The aim of this study was to investigate the association between those MMPs and variceal bleeding (VB). Methods Fifteen controls, 12 patients with acute ulcer bleeding (UB) group, 37 patients with varix (V group), and 35 patients with acute VB group were enrolled. Serum was obtained to measure MMP-2 and -9 activity by zymogram protease assays. Results The activity levels of these compounds were compared with the controls' median value. The median MMP-9 activity was 1.0 in controls, 1.05 in the UB group, 0.43 in the V group, and 0.96 in the VB group. The level of MMP-9 activity was higher in the VB group than in the V group (p<0.001). In the VB group, there was a signifi cant decrease in MMP-9 activity over time after bleeding (p<0.001). The median MMP-2 activity level was 1.0 in controls, 1.01 in the UB group, 1.50 in the V group, and 1.55 in the VB group. The level of MMP-2 activity was similar in the VB and V groups. Conclusions The level of MMP-9 activity increased in association with VB. The role of MMP-9 in the pathogenesis of VB should be verified. PMID:22570756

  15. Digital radiology using active matrix readout of amorphous selenium: detectors with high voltage protection.

    PubMed

    Zhao, W; Law, J; Waechter, D; Huang, Z; Rowlands, J A

    1998-04-01

    A flat-panel x-ray imaging detector is being investigated for digital radiography and fluoroscopy. The detector uses a layer of amorphous selenium (a-Se) to convert x rays to a charge image, which is then electronically read out with a two-dimensional array of thin film transistors (TFTs). In order to sensitize the a-Se layer to x rays, a high voltage (of the order of several thousand volts) is applied to its top surface. The TFTs, which are at the bottom surface of the a-Se layer, are not subjected to any high voltage under normal radiological operational conditions since the pixel potential is < 10 V. However under a fault condition where these two events occur simultaneously: (1) suspended detector scan; and (2) an x-ray exposure more than ten times higher than normal, the voltage on the TFTs could rise to a damaging value. This paper describes a method for protecting the TFTs from high voltage damage under this fault condition. It employs a dual-gate TFT structure, one gate is for scanning control and the other is connected to the pixel electrode for high voltage protection. Before the pixel potential reaches a damaging value, the protection gate turns on the TFT automatically and drains excess charge away from the pixel thus providing a safe pixel saturation potential. In this paper, the characteristic curves of dual-gate TFTs are studied both theoretically and experimentally. The pixel x-ray response for imaging detectors with high voltage protection are predicted, and it is shown that with practical TFT designs the detector can provide a safe pixel saturation potential as well as satisfy the dynamic range required for diagnostic x-ray imaging applications.

  16. Silicon pixel detector prototyping in SOI CMOS technology

    NASA Astrophysics Data System (ADS)

    Dasgupta, Roma; Bugiel, Szymon; Idzik, Marek; Kapusta, Piotr; Kucewicz, Wojciech; Turala, Michal

    2016-12-01

    The Silicon-On-Insulator (SOI) CMOS is one of the most advanced and promising technology for monolithic pixel detectors design. The insulator layer that is implemented inside the silicon crystal allows to integrate sensors matrix and readout electronic on a single wafer. Moreover, the separation of electronic and substrate increases also the SOI circuits performance. The parasitic capacitances to substrate are significantly reduced, so the electronic systems are faster and consume much less power. The authors of this presentation are the members of international SOIPIX collaboration, that is developing SOI pixel detectors in 200 nm Lapis Fully-Depleted, Low-Leakage SOI CMOS. This work shows a set of advantages of SOI technology and presents possibilities for pixel detector design SOI CMOS. In particular, the preliminary results of a Cracow chip are presented.

  17. 1alpha,25(OH)2D3 is an autocrine regulator of extracellular matrix turnover and growth factor release via ERp60 activated matrix vesicle metalloproteinases.

    PubMed

    Boyan, Barbara D; Wong, Kevin L; Fang, Mimi; Schwartz, Zvi

    2007-03-01

    Growth plate chondrocytes produce proteoglycan-rich type II collagen extracellular matrix (ECM). During cell maturation and hypertrophy, ECM is reorganized via a process regulated by 1alpha,25(OH)(2)D(3) and involving matrix metalloproteinases (MMPs), including MMP-3 and MMP-2. 1alpha,25(OH)(2)D(3) regulates MMP incorporation into matrix vesicles (MVs), where they are stored until released. Like plasma membranes (PM), MVs contain the 1alpha,25(OH)(2)D(3)-binding protein ERp60, phospholipase A(2) (PLA(2)), and caveolin-1, but appear to lack nuclear Vitamin D receptors (VDRs). Chondrocytes produce 1alpha,25(OH)(2)D(3) (10(-8)M), which binds ERp60, activating PLA(2), and resulting lysophospholipids lead to MV membrane disorganization, releasing active MMPs. MV MMP-3 activates TGF-beta1 stored in the ECM as large latent TGF-beta1 complexes, consisting of latent TGF-beta1 binding protein, latency associated peptide, and latent TGF-beta1. Others have shown that MMP-2 specifically activates TGF-beta2. TGF-beta1 regulates 1alpha,25(OH)(2)D(3)-production, providing a mechanism for local control of growth factor activation. 1alpha,25(OH)(2)D(3) activates PKCalpha in the PM via ERp60-signaling through PLA(2), lysophospholipid production, and PLCbeta. It also regulates distribution of phospholipids and PKC isoforms between MVs and PMs, enriching the MVs in PKCzeta. Direct activation of MMP-3 in MVs requires ERp60. However, when MVs are treated with 1alpha,25(OH)(2)D(3), PKCzeta activity is decreased and PKCalpha is unaffected, suggesting a more complex feedback mechanism, potentially involving MV lipid signaling.

  18. Tissue inhibitors of matrix metalloproteinases 1 and 2 and matrix metalloproteinase activity in the serum and lungs of mice with lewis lung carcinoma.

    PubMed

    Kisarova, Ya A; Korolenko, T A

    2012-10-01

    We studied the content of tissue inhibitors of matrix metalloproteinases 1 and 2 (TIMP-1 and TIMP-2) and activities of matrix metalloproteinases (MMP) in the serum and lungs of mice with Lewis lung carcinoma metastasizing into the lung. Metastasizing was associated with increased serum content of TIMP-1 and TIMP-2 (only on day 20 at the terminal stage of the tumor process). These data confirm the hypothesis on pro-tumorigenic role of TIMP-1 in the serum. Locally, the development of metastases was associated with a decrease in TIPM-1 concentration (day 7), an increase in TIMP-2 concentration (days 7 and 20), and elevated activity of MMP at all terms of the study (days 7, 15, and 20). Increased concentration of TIMP-2 in the lungs (but not in the serum) can be regarded as an indicator of Lewis lung carcinoma metastasizing.

  19. Amplified pixel sensor architectures for low dose computed tomography using silicon thin film technology

    NASA Astrophysics Data System (ADS)

    Taghibakhsh, F.; Karim, K. S.

    2007-03-01

    Cone beam computed tomography (CBCT) has been recently reported using flat panel imagers (FPI). Here, detector technology capable of high speed imaging, high spatial resolution, large volume coverage, better contrast resolution and, in particular, lowered patient dose is required. Employing active matrix flat panel imagers (AMFPIs) as cone beam CT detectors has been proposed as a solution for improving volume coverage, contrast and resolution; however, clinical evaluations have shown that they suffer from low speed read out. Unlike passive pixel architecture which is currently the state-of-the-art technology for AMFPIs, our preliminary studies have shown that novel amplified pixel sensor (APS) architectures can overcome the low readout speed, and moreover, they provide gain which can be traded for higher frame rate and lower X-ray doses. Although APS architectures can meet the high dynamic range and low noise requirements of CT imaging, linearity and variations between pixel characteristics are major issues. In this study we will investigate novel APS architectures to address these concerns.

  20. The electro-mechanical integration of the NA62 GigaTracker time tagging pixel detector

    NASA Astrophysics Data System (ADS)

    Morel, M.; Kluge, A.; Aglieri Rinella, G.; Carassiti, V.; Ceccucci, A.; Daguin, J.; Fiorini, M.; Jarron, P.; Kaplon, J.; Mapelli, A.; Marchetto, F.; Noy, M.; Nuessle, G.; Perktold, L.; Petagna, P.; Riedler, P.

    2010-12-01

    The NA62 GigaTracker is a low mass time tagging hybrid pixel detector operating in a beam with a particle rate of 750 MHz. It consists of three stations with a sensor size of 60 × 27mm2 containing 18000 pixels, each 300 × 300μm2. The active area is connected to a matrix of 2 × 5 pixel ASICs, which time tag the arrival of the particles with a binning of 100 ps. The detector operates in vacuum at -20 to 0°C and the material budget per station must be below 0.5% X0. Due to the high radiation environment of 2 × 1014 1 MeV neutron equivalent cm-2/yr-1 it is planned to exchange the detector modules regularly. The low material budget, cooling requirements and the request for easy module access has driven the electro-mechanical integration of the GigaTracker, which is presented in this paper.

  1. 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

  2. Pixel Analysis and Plasma Dynamics Characterized by Photospheric Spectral Data

    NASA Astrophysics Data System (ADS)

    Rasca, A.; Chen, J.; Pevtsov, A. A.

    2015-12-01

    Continued advances in solar observations have led to higher-resolution magnetograms and surface (photospheric) images, revealing bipolar magnetic features operating near the resolution limit during emerging flux events and other phenomena used to predict solar eruptions responsible for geomagnetic plasma disturbances. However, line of sight (LOS) magnetogram pixels only contain the net uncanceled magnetic flux, which is expected to increase for fixed regions as resolution limits improve. A pixel dynamics model utilizing Stokes I spectral profiles was previously-used to quantify changes in the Doppler shift, width, asymmetry, and tail flatness of Fe I lines at 6301.5 and 6302.5 Å and used pixel-by-pixel line profile fluctuations to characterize quiet and active regions on the Sun. We use this pixel dynamics model with circularly polarized photospheric data (e.g., SOLIS data) to estimate plasma dynamic properties at a sub-pixel level. The analysis can be extended to include the full Stokes parameters and study signatures of magnetic fields and coupled plasma properties on sub-pixel scales.

  3. 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

    2015-04-09

    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.

  4. Pixel electronics for the ATLAS experiment

    NASA Astrophysics Data System (ADS)

    Fischer, P.

    2001-06-01

    The ATLAS experiment at LHC will use 3 barrel layers and 2×5 disks of silicon pixel detectors as the innermost elements of the semiconductor tracker. The basic building blocks are pixel modules with an active area of 16.4 mm×60.8 mm which include an n + on n-type silicon sensor and 16 VLSI front-end (FE) chips. Every FE chip contains a low power, high speed charge sensitive preamplifier, a fast discriminator, and a readout system which operates at the 40 MHz rate of LHC. The addresses of hit pixels (as well as a low resolution pulse height information) are stored on the FE chips until arrival of a level 1 trigger signal. Hits are then transferred to a module controller chip (MCC) which collects the data of all 16 FE chips, builds complete events and sends the data through two optical links to the data acquisition system. The MCC receives clock and data through an additional optical link and provides timing and configuration information for the FE chips. Two additional chips are used to amplify and decode the pin diode signal and to drive the VCSEL laser diodes of the optical links.

  5. 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.

  6. Development of active matrix flat panel imagers incorporating thin layers of polycrystalline HgI(2) for mammographic x-ray imaging.

    PubMed

    Jiang, Hao; Zhao, Qihua; Antonuk, Larry E; El-Mohri, Youcef; Gupta, Tapan

    2013-02-07

    Active matrix flat-panel imagers (AMFPIs) offer many advantages and have become ubiquitous across a wide variety of medical x-ray imaging applications. However, for mammography, the imaging performance of conventional AMFPIs incorporating CsI:Tl scintillators or a-Se photoconductors is limited by their relatively modest signal-to-noise ratio (SNR), particularly at low x-ray exposures or high spatial resolution. One strategy for overcoming this limitation involves the use of a high gain photoconductor such as mercuric iodide (HgI(2)) which has the potential to improve the SNR by virtue of its low effective work function (W(EFF)). In this study, the performance of direct-detection AMFPI prototypes employing relatively thin layers of polycrystalline HgI(2) operated under mammographic irradiation conditions over a range of 0.5 to 16.0 mR is presented. High x-ray sensitivity (corresponding to W(EFF) values of ∼19 eV), low dark current (<0.1 pA mm(-2)) and good spatial resolution, largely limited by the size of the pixel pitch, were observed. For one prototype, a detective quantum efficiency of ∼70% was observed at an x-ray exposure of ∼0.5 mR at 26 kVp.

  7. WFC3 Pixel Area Maps

    NASA Astrophysics Data System (ADS)

    Kalirai, J. S.; Cox, C.; Dressel, L.; Fruchter, A.; Hack, W.; Kozhurina-Platais, V.; Mack, J.

    2010-04-01

    We present the pixel area maps (PAMs) for the WFC3/UVIS and WFC3/IR detectors, and discuss the normalization of these images. HST processed flt images suffer from geometric distortion and therefore have pixel areas that vary on the sky. The counts (electrons) measured for a source on these images depends on the position of the source on the detector, an effect that is implicitly corrected when these images are multidrizzled into drz files. The flt images can be multiplied by the PAMs to yield correct and uniform counts for a given source irrespective of its location on the image. To ensure consistency between the count rate measured for sources in drz images and near the center of flt images, we set the normalization of the PAMs to unity at a reference pixel near the center of the UVIS mosaic and IR detector, and set the SCALE in the IDCTAB equal to the square root of the area of this reference pixel. The implications of this choice for photometric measurements are discussed.

  8. Edge pixel response studies of edgeless silicon sensor technology for pixellated imaging detectors

    NASA Astrophysics Data System (ADS)

    Maneuski, D.; Bates, R.; Blue, A.; Buttar, C.; Doonan, K.; Eklund, L.; Gimenez, E. N.; Hynds, D.; Kachkanov, S.; Kalliopuska, J.; McMullen, T.; O'Shea, V.; Tartoni, N.; Plackett, R.; Vahanen, S.; Wraight, K.

    2015-03-01

    Silicon sensor technologies with reduced dead area at the sensor's perimeter are under development at a number of institutes. Several fabrication methods for sensors which are sensitive close to the physical edge of the device are under investigation utilising techniques such as active-edges, passivated edges and current-terminating rings. Such technologies offer the goal of a seamlessly tiled detection surface with minimum dead space between the individual modules. In order to quantify the performance of different geometries and different bulk and implant types, characterisation of several sensors fabricated using active-edge technology were performed at the B16 beam line of the Diamond Light Source. The sensors were fabricated by VTT and bump-bonded to Timepix ROICs. They were 100 and 200 μ m thick sensors, with the last pixel-to-edge distance of either 50 or 100 μ m. The sensors were fabricated as either n-on-n or n-on-p type devices. Using 15 keV monochromatic X-rays with a beam spot of 2.5 μ m, the performance at the outer edge and corners pixels of the sensors was evaluated at three bias voltages. The results indicate a significant change in the charge collection properties between the edge and 5th (up to 275 μ m) from edge pixel for the 200 μ m thick n-on-n sensor. The edge pixel performance of the 100 μ m thick n-on-p sensors is affected only for the last two pixels (up to 110 μ m) subject to biasing conditions. Imaging characteristics of all sensor types investigated are stable over time and the non-uniformities can be minimised by flat-field corrections. The results from the synchrotron tests combined with lab measurements are presented along with an explanation of the observed effects.

  9. Low level laser therapy modulates viability, alkaline phosphatase and matrix metalloproteinase-2 activities of osteoblasts.

    PubMed

    Oliveira, Flávia Amadeu de; Matos, Adriana Arruda; Matsuda, Sandra Satiko; Buzalaf, Marília Afonso Rabelo; Bagnato, Vanderley Salvador; Machado, Maria Aparecida de Andrade Moreira; Damante, Carla Andreotti; Oliveira, Rodrigo Cardoso de; Peres-Buzalaf, Camila

    2017-04-01

    Low level laser therapy (LLLT) has been shown to stimulate bone cell metabolism but their impact on the matrix metalloproteinase (MMP) expression and activity is little explored. This study evaluated the influence of LLLT at two different wavelengths, red and infrared, on MC3T3-E1 preosteoblast viability, alkaline phosphatase (ALP) and MMP-2 and -9 activities. To accomplish this, MC3T3-E1 cells were irradiated with a punctual application of either red (660nm; InGaAIP active medium) or infrared (780nm; GaAlAs active medium) lasers both at a potency of 20mW, energy dose of 0.08 or 0.16J, and energy density of 1.9J/cm(2) or 3.8J/cm(2), respectively. The control group received no irradiation. Cellular viability, ALP and MMP-2 and -9 activities were assessed by MTT assay, enzymatic activity and zymography, respectively, at 24, 48 and 72h. The treatment of cells with both red and infrared lasers significantly increased the cellular viability compared to the non-irradiated control group at 24 and 48h. The ALP activity was also up modulated in infrared groups at 24 and 72h, depending on the energy densities. In addition, the irradiation with red laser at the energy density of 1.9J/cm(2) promoted an enhancement of MMP-2 activity at 48 and 72h. However, no differences were observed for the MMP-9 activity. In conclusion, when used at these specific parameters, LLL modulates both preosteoblast viability and differentiation highlighted by the increased ALP and MMP-2 activities induced by irradiation.

  10. Prospects for treating osteoarthritis: enzyme–protein interactions regulating matrix metalloproteinase activity

    PubMed Central

    Meszaros, Evan

    2012-01-01

    Primary osteoarthritis (OA) is a musculoskeletal disorder of unknown etiology. OA is characterized by an imbalance between anabolism and catabolism in, and altered homeostasis of articular cartilage. Matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motif are upregulated in OA joints. Extracellular matrix (ECM) proteins are critical for resistance to compressive forces and for maintaining the tensile properties of the tissue. Tissue inhibitor of metalloproteinases (TIMPs) is the endogenous inhibitor of MMPs, but in OA, TIMPs do not effectively neutralize MMP activity. Upregulation of MMP gene expression occurs in OA in a milieu of proinflammatory cytokines such as interleukin (IL)-1, IL-6 and tumor necrosis factor α. Presently, the medical therapy of OA includes mainly nonsteroidal anti-inflammatory drugs and corticosteroids which dampen pain and inflammation but appear to have little effect on restoring joint function. Experimental interventions to restore the imbalance between anabolism and catabolism include small molecule inhibitors of MMP subtypes or inhibitors of the interaction between IL-1 and its receptor. Although these agents have some positive effects on reducing MMP subtype activity they have little efficacy at the clinical level. MMP-9 is one MMP subtype implicated in the degradation of articular cartilage ECM proteins. MMP-9 was found in OA synovial fluid as a complex with neutrophil gelatinase-associated lipocalin (NGAL) which protected MMP-9 from autodegradation. Suppressing NGAL synthesis or promoting NGAL degradation may result in reducing the activity of MMP-9. We also propose initiating a search for enzyme–protein interactions to dampen other MMP subtype activity which could suppress ECM protein breakdown. PMID:23342237

  11. Differential expression and activity of matrix metalloproteinases 2 and 9 in canine early placenta.

    PubMed

    Diessler, M; Ventureira, M; Hernandez, R; Sobarzo, C; Casas, L; Barbeito, C; Cebral, E

    2017-02-01

    The zonary and endotheliochorial dog placenta is the most invasive placenta of carnivores. The importance of matrix metalloproteinases (MMP) in placenta invasiveness has been determined in several mammals including species with haemochorial, epitheliochorial and endotheliochorial placentation. Regarding the latter, the expression of MMP enzymes has been studied in the cat and the mature canine placenta. The aim of this study was to analyse the expression and activity of MMP-2 and MMP-9 in the early dog placenta. Placentae from 18 to 30 days of pregnancy were collected from four bitches. Two placentae from each bitch were analysed. Placental tissue from one uterine horn was fixed in formaldehyde for immunohistochemistry, while marginal haematoma, labyrinth, non-implantative and implantative endometrium from the contralateral horn were immediately frozen in dry ice for the analysis of MMP expression (Western blot [WB]) and activity (zymography). MMP-2 and MMP-9 were evidenced in the labyrinth, maternal glands and marginal haematoma; this finding was directly correlated with levels of MMP expression by WB, and with the activity of MMP-2, mainly in the haematoma (the area of major remodelling of tissues). Thus, although MMP-9 is well expressed in the early canine placenta, it is not active. Given the important role of MMPs for invasiveness, maternal-foetal angiogenesis and the establishment of a correct foetal nutrition, the results are consistent with the findings in other species in which the MMP-2 activation precedes the MMP-9 one in early placentation.

  12. An integrating CMOS APS for X-ray imaging with an in-pixel preamplifier

    NASA Astrophysics Data System (ADS)

    Abdalla, M. A.; Fröjdh, C.; Petersson, C. S.

    2001-06-01

    We present in this paper an integrating CMOS Active Pixel Sensor (APS) circuit coated with scintillator type sensors for intra-oral dental X-ray imaging systems. The photosensing element in the pixel is formed by the p-diffusion on the n-well diode. The advantage of this photosensor is its very low direct absorption of X-rays compared to the other available photosensing elements in the CMOS pixel. The pixel features an integrating capacitor in the feedback loop of a preamplifier of a finite gain in order to increase the optical sensitivity. To verify the effectiveness of this in-pixel preamplification, a prototype 32×80 element CMOS active pixel array was implemented in a 0.8 μm CMOS double poly, n-well process with a pixel pitch of 50 μm. Measured results confirmed the improved optical sensitivity performance of the APS. Various measurements on device performance are presented.

  13. 8-Iso-prostaglandin f(2alpha) reduces trophoblast invasion and matrix metalloproteinase activity.

    PubMed

    Staff, A C; Ranheim, T; Henriksen, T; Halvorsen, B

    2000-06-01

    Preeclampsia is a common pregnancy complication in the latter half of gestation diagnosed by hypertension and proteinuria. A key feature of preeclampsia is an altered placentation with reduced trophoblast invasion. Normal placentation requires controlled invasion of trophoblasts into the maternal uterine wall, with secretion of specific proteolytic enzymes able to degrade basement membranes and extracellular matrix, such as the matrix metalloproteinases (MMPs). 8-Iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) is a marker of oxidative stress in vivo and is biologically active. We have recently reported an elevated content of free 8-iso-PGF(2alpha) in preeclamptic gestational tissue at delivery. Assuming an elevated level of 8-iso-PGF(2alpha) during the invasion period of the pregnancy, we hypothesized that 8-iso-PGF(2alpha) could reduce invasion of JAR cells, a choriocarcinoma cell line. We investigated JAR cell invasion with 2 types of Transwell assays and demonstrated that 8-iso-PGF(2alpha) (10 micromol/L) resulted in reduced cell invasion in both the colorimetric and radioactivity Transwell assays (P<0.01). Zymograms revealed reduced MMP-2 and MMP-9 activity in conditioned media from JAR cells incubated with 8-iso-PGF(2alpha) (10 micromol/L) (P<0.02). 8-Iso-PGF(2alpha) (10 micromol/L) also reduced the collagenase type IV activity in the conditioned media of JAR cells (P=0.04). No effects on MMP-2 and MMP-9 mRNA levels were observed after incubation with 8-iso-PGF(2alpha) (10 micromol/L), whereas protein levels were significantly decreased (P<0.02), suggesting a posttranscriptional regulation. We hypothesize a potential role for 8-iso-PGF(2alpha) in the reduced trophoblast invasion in preeclampsia.

  14. Detecting seismic activity with a covariance matrix analysis of data recorded on seismic arrays

    NASA Astrophysics Data System (ADS)

    Seydoux, L.; Shapiro, N. M.; de Rosny, J.; Brenguier, F.; Landès, M.

    2016-03-01

    Modern seismic networks are recording the ground motion continuously at the Earth's surface, providing dense spatial samples of the seismic wavefield. The aim of our study is to analyse these records with statistical array-based approaches to identify coherent time-series as a function of time and frequency. Using ideas mainly brought from the random matrix theory, we analyse the spatial coherence of the seismic wavefield from the width of the covariance matrix eigenvalue distribution. We propose a robust detection method that could be used for the analysis of weak and emergent signals embedded in background noise, such as the volcanic or tectonic tremors and local microseismicity, without any prior knowledge about the studied wavefields. We apply our algorithm to the records of the seismic monitoring network of the Piton de la Fournaise volcano located at La Réunion Island and composed of 21 receivers with an aperture of ˜15 km. This array recorded many teleseismic earthquakes as well as seismovolcanic events during the year 2010. We show that the analysis of the wavefield at frequencies smaller than ˜0.1 Hz results in detection of the majority of teleseismic events from the Global Centroid Moment Tensor database. The seismic activity related to the Piton de la Fournaise volcano is well detected at frequencies above 1 Hz.

  15. Performance and modeling of active metal-matrix composites manufactured by ultrasonic additive manufacturing

    NASA Astrophysics Data System (ADS)

    Hahnlen, Ryan; Dapino, Marcelo J.

    2011-04-01

    This paper presents the development and characterization of active aluminum-matrix composites manufactured by Ultrasonic Additive Manufacturing (UAM), an emerging rapid prototyping process based on ultrasonic metal welding. The primary benefit of UAM over other metal-matrix fabrication processes is the low process temperatures, as low as 25 °C. UAM thus provides unprecedented opportunities to develop adaptive structures with seamlessly embedded smart materials and electronic components without degrading the properties that make these materials and components attractive. The objective of this research is to develop UAM composites with aluminum matrices and embedded shape memory NiTi, magnetostrictive Galfenol (FeGa), and polyvinylidene fluoride (PVDF) phases. The paper is focused on the thermally induced strain response and stiffness behavior of NiTi-Al composites, the actuation properties of FeGa-Al composites, and the embedded sensing capabilities of PVDF-Al composites. We observe up to a 10% increase over room temperature stiffness for NiTi-Al composites and a magnetomechanical response in the FeGa-Al composite up to 52.4 μɛ. The response of the PVDF-Al composite to harmonic loads is observed over a frequency range of 10 to 1000 Hz.

  16. 92-kd type IV collagenase (matrix metalloproteinase-9) activity in human amniochorion increases with labor.

    PubMed Central

    Vadillo-Ortega, F.; González-Avila, G.; Furth, E. E.; Lei, H.; Muschel, R. J.; Stetler-Stevenson, W. G.; Strauss, J. F.

    1995-01-01

    To determine whether specific collagenolytic enzymes are expressed in human fetal membranes with labor, we examined gelatinase activity in extracts of amniochorion by zymography. The 92-kd gelatinase (MMP-9) was barely detectable in extracts of fetal membranes before the onset of labor but was readily demonstrable in extracts prepared from membranes isolated from laboring women or membranes collected immediately after delivery. In contrast, the 72-kd gelatinase (MMP-2) was detectable in extracts from pre- and post-labor membranes. Ethylenediaminetetracetic acid and the tissue inhibitor of metalloproteinases, TIMP-1, inhibited the gelatinase activities detected by zymography, confirming that the enzymes are metalloproteinase. Assay of amniochorion gelatinase activity using a radiolabeled denatured collagen substrate revealed a more than twofold increase in activity comparing pre-labor with post-labor fetal membrane extracts. A function-blocking anti-MMP-9 monoclonal antibody inhibited pre-labor membrane gelatinase activity by approximately 11.5%, which was only slightly greater inhibition than observed with irrelevant monoclonal antibodies. However, post-labor membrane gelatinase activity was reduced by 53% by the function-blocking antibody, indicating that MMP-9 is a major contributor to the increased gelatinase activity extractable from post-labor membranes. Western blot analyses demonstrated increased MMP-9 protein in amniochorion extracts after onset of labor. MMP-9 protein and mRNA were co-localized in amnion epithelium, underlying macrophages and chorion laeve trophoblast and decidual cells after labor. We conclude that 1) MMP-9 activity and protein in human amniochorion increases with labor and 2) MMP-9 is expressed by amnion epithelium, macrophages and chorion laeve trophoblast and decidual cells. The increased expression of MMP-9 may result in degradation of the extracellular matrix of the fetal membranes and facilitate their rupture under both

  17. Front-end electronics for DEPFET pixel detectors at SuperBelle (BELLE II)

    NASA Astrophysics Data System (ADS)

    Krüger, Hans; Depfet Collaboration

    2010-05-01

    This article gives an overview of the front-end electronics development for the DEPFET pixel vertex detector at the Super KEK-B experiment (BELLE II). The planned upgrade of the KEK-B factory will lead to a peak luminosity of 8×1035 cm-2 s-1. This increase in luminosity (×50 compared to the existing experiment) will make high demands on the performance of the vertex detector. The proposed two layer vertex detector consists of 'all-silicon' modules: the read-out and control ASICs will be bump bonded on the rigid edges of the DEPFET substrate whereas in the region of the active pixel matrix the substrate will be thinned down to 50 μm. The front-end electronics is subdivided in three different ASIC types: one chip will provide up to 20 V output swing for the control voltages of the DEPFET matrix (SWITCHER), the current signals are being digitized by a multichannel ADC chip (DCD) and the processing of the digital data and module control functionality is implemented in a data handling chip (DHP). An overview of the module concept and the status of the developments including results of current prototype chips will be given.

  18. Development and simulation results of a sparsification and readout circuit for wide pixel matrices

    NASA Astrophysics Data System (ADS)

    Gabrielli, A.; Giorgi, F.; Morsani, F.; Villa, M.

    2011-06-01

    In future collider experiments, the increasing luminosity and centre of mass energy are rising challenging problems in the design of new inner tracking systems. In this context we develop high-efficiency readout architectures for large binary pixel matrices that are meant to cope with the high-stressing conditions foreseen in the innermost layers of a tracker [The SuperB Conceptual Design Report, INFN/AE-07/02, SLAC-R-856, LAL 07-15, Available online at: http://www.pi.infn.it/SuperB]. We model and design digital readout circuits to be integrated on VLSI ASICs. These architectures can be realized with different technology processes and sensors: they can be implemented on the same silicon sensor substrate of a CMOS MAPS devices (Monolithic Active Pixel Sensor), on the CMOS tier of a hybrid pixel sensor or in a 3D chip where the digital layer is stacked on the sensor and the analog layers [V. Re et al., Nuc. Instr. and Meth. in Phys. Res. A, doi:10.1016/j.nima.2010.05.039]. In the presented work, we consider a data-push architecture designed for a sensor matrix of an area of about 1.3 cm 2 with a pitch of 50 microns. The readout circuit tries to take great advantage of the high density of in-pixel digital logic allowed by vertical integration. We aim at sustaining a rate density of 100 Mtrack ṡ s -1 ṡ cm -2 with a temporal resolution below 1 μs. We show how this architecture can cope with these stressing conditions presenting the results of Monte Carlo simulations.

  19. 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.

  20. Toward active-matrix lab-on-a-chip: programmable electrofluidic control enabled by arrayed oxide thin film transistors.

    PubMed

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

    2012-01-21

    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×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(2) V(-1) s(-1), low-temperature processing and transparency for potential spectroscopy and imaging. Several electrofluidic functionalities are demonstrated using a simple 2 × 5 electrode array connected to a 2 × 5 IGZO thin film transistor array with the semiconductor channel width of 50 μm and mobility of 6.3 cm(2) V(-1) s(-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.

  1. Gelatinolytic activity of matrix metalloproteinase in lung cancer studied using film in situ zymography stamp method.

    PubMed

    Kaji, Masahiro; Moriyama, Satoru; Sasaki, Hidefumi; Saitoh, Yushi; Kiriyama, Masanobu; Fukai, Ichiro; Yamakawa, Yosuke; Mitsui, Akira; Toyama, Tatsuya; Nemori, Ryoichi; Fujii, Yoshitaka

    2003-02-01

    In this study, we investigated activity of matrix metalloproteinase (MMP) of lung cancer by newly developed film in situ zymography (FIZ) stamp method, which allows visual localization of gelatinolytic activity within the cut surface of a tumor. We performed FIZ stamp method and conventional gelatin zymography in 39 resected specimen of lung cancer. The degree of gelatinolytic activity was scored (FIZ score) and correlated with the clinicopathological factors of the tumor. FIZ score of normal lung was very low. Lung cancer tissue had consistently higher FIZ score than the matched normal lung tissue. There were statistically significant differences in the FIZ score according to the pathological stage (P = 0.0015), nodal status (P = 0.0007) and lymphatic invasion (P = 0.0004). Direct correlation was observed between the FIZ score and MMP-2 activity (rho = 0.568, P = 0.0030) as quantitated using conventional gelatin zymography. MMP-2 may play an important role in the lymphatic invasion of lung cancer. FIZ stamp method may be a simple and useful diagnostic aid for the presence of cancer cells in the resected specimen.

  2. DP-b99 Modulates Matrix Metalloproteinase Activity and Neuronal Plasticity

    PubMed Central

    Yeghiazaryan, Marine; Rutkowska-Wlodarczyk, Izabela; Konopka, Anna; Wilczyński, Grzegorz M.; Melikyan, Armenuhi; Korkotian, Eduard; Kaczmarek, Leszek; Figiel, Izabela

    2014-01-01

    DP-b99 is a membrane-activated chelator of zinc and calcium ions, recently proposed as a therapeutic agent. Matrix metalloproteinases (MMPs) are zinc-dependent extracellularly operating proteases that might contribute to synaptic plasticity, learning and memory under physiological conditions. In excessive amounts these enzymes contribute to a number of neuronal pathologies ranging from the stroke to neurodegeneration and epileptogenesis. In the present study, we report that DP-b99 delays onset and severity of PTZ-induced seizures in mice, as well as displays neuroprotective effect on kainate excitotoxicity in hippocampal organotypic slices and furthermore blocks morphological reorganization of the dendritic spines evoked by a major neuronal MMP, MMP-9. Taken together, our findings suggest that DP-b99 may inhibit neuronal plasticity driven by MMPs, in particular MMP-9, and thus may be considered as a therapeutic agent under conditions of aberrant plasticity, such as those subserving epileptogenesis. PMID:24918931

  3. 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.

  4. Matrix metalloproteinase 13 mediates nitric oxide activation of endothelial cell migration

    PubMed Central

    López-Rivera, Esther; Lizarbe, Tania R.; Martínez-Moreno, Mónica; López-Novoa, José Miguel; Rodríguez-Barbero, Alicia; Rodrigo, José; Fernández, Ana Patricia; Álvarez-Barrientos, Alberto; Lamas, Santiago; Zaragoza, Carlos

    2005-01-01

    To explore the mechanisms by which NO elicits endothelial cell (EC) migration we used murine and bovine aortic ECs in an in vitro wound-healing model. We found that exogenous or endogenous NO stimulated EC migration. Moreover, migration was significantly delayed in ECs derived from endothelial NO synthase-deficient mice compared with WT murine aortic EC. To assess the contribution of matrix metalloproteinase (MMP)-13 to NO-mediated EC migration, we used RNA interference to silence MMP-13 expression in ECs. Migration was delayed in cells in which MMP-13 was silenced. In untreated cells MMP-13 was localized to caveolae, forming a complex with caveolin-1. Stimulation with NO disrupted this complex and significantly increased extracellular MMP-13 abundance, leading to collagen breakdown. Our findings show that MMP-13 is an important effector of NO-activated endothelial migration. PMID:15728377

  5. DP-b99 modulates matrix metalloproteinase activity and neuronal plasticity.

    PubMed

    Yeghiazaryan, Marine; Rutkowska-Wlodarczyk, Izabela; Konopka, Anna; Wilczyński, Grzegorz M; Melikyan, Armenuhi; Korkotian, Eduard; Kaczmarek, Leszek; Figiel, Izabela

    2014-01-01

    DP-b99 is a membrane-activated chelator of zinc and calcium ions, recently proposed as a therapeutic agent. Matrix metalloproteinases (MMPs) are zinc-dependent extracellularly operating proteases that might contribute to synaptic plasticity, learning and memory under physiological conditions. In excessive amounts these enzymes contribute to a number of neuronal pathologies ranging from the stroke to neurodegeneration and epileptogenesis. In the present study, we report that DP-b99 delays onset and severity of PTZ-induced seizures in mice, as well as displays neuroprotective effect on kainate excitotoxicity in hippocampal organotypic slices and furthermore blocks morphological reorganization of the dendritic spines evoked by a major neuronal MMP, MMP-9. Taken together, our findings suggest that DP-b99 may inhibit neuronal plasticity driven by MMPs, in particular MMP-9, and thus may be considered as a therapeutic agent under conditions of aberrant plasticity, such as those subserving epileptogenesis.

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

    PubMed Central

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

    2014-01-01

    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. PMID:25234244

  7. SAR Image Complex Pixel Representations

    SciTech Connect

    Doerry, Armin W.

    2015-03-01

    Complex pixel values for Synthetic Aperture Radar (SAR) images of uniform distributed clutter can be represented as either real/imaginary (also known as I/Q) values, or as Magnitude/Phase values. Generally, these component values are integers with limited number of bits. For clutter energy well below full-scale, Magnitude/Phase offers lower quantization noise than I/Q representation. Further improvement can be had with companding of the Magnitude value.

  8. Single-pixel hyperspectral imaging

    NASA Astrophysics Data System (ADS)

    Suo, Jinli; Wang, Yuwang; Bian, Liheng; Dai, Qionghai

    2016-10-01

    Conventional multispectral imaging methods detect photons of a 3D hyperspectral data cube separately either in the spatial or spectral dimension using array detectors, and are thus photon inefficient and spectrum range limited. Besides, they are usually bulky and highly expensive. To address these issues, this paper presents single-pixel multispectral imaging techniques, which are of high sensitivity, wide spectrum range, low cost and light weight. Two mechanisms are proposed, and experimental validation are also reported.

  9. Expression and activity of matrix metalloproteinases in the uterus of bitches after spontaneous and induced abortion.

    PubMed

    Kanca, H; Walter, I; Miller, I; Schäfer-Somi, S; Izgur, H; Aslan, S

    2011-04-01

    Aim of this study was to determine the intrauterine activity of matrix metalloproteinases (MMP)-2 and -9 after cessation of the local effect of progesterone. For this purpose, pregnancy was terminated in 10 bitches at mid-gestation with the progesterone receptor antagonist aglepristone (10 mg/kg body weight, sc, Alizine®; Virbac, France) at two subsequent days (group IRA = induced resorption/abortion). The IRA group was divided into two subgroups (Group I, n = 5, days 25-35 of pregnancy; group II, n = 5, days 36-45). Five further bitches were introduced with beginning abortion (group SRA = spontaneous resorption/abortion). Seven healthy bitches between day 25 and 45 of gestation served as controls. After ovariohysterectomy at the end of abortion and between days 25 and 45 of gestation, respectively, the distribution and activity of collagenases were investigated by immunohistochemistry and gelatin zymography. At placental sites, MMP-2 activity in the endometrium was significantly lower in IRA groups than in the SRA group (33.7 ± 11.8% and 39.3 ± 5.4% vs 52.2 ± 10.2%, p < 0.05); however, MMP-2 expression was lowest in the control group (control: 21.4 ± 6.3%; p < 0.01) and similarly in the myometrium (controls: 13.1 ± 2.5%; p < 0.05). MMP-9 activity was also lower in the endometrium and myometrium of the control group in comparison to SRA and IRA groups (11.8 ± 3.2%; p < 0.01 and 28.4 ± 32.8%; p < 0.05). At interplacental sites, the amount of active collagenases in the myometrium was significantly lower in the control group. It is concluded that the blockade of the biological progesterone effect was associated with an increase in activity of both collagenases.

  10. Minimum Variance Approaches to Ultrasound Pixel-Based Beamforming.

    PubMed

    Nguyen, Nghia Q; Prager, Richard W

    2017-02-01

    We analyze the principles underlying minimum variance distortionless response (MVDR) beamforming in order to integrate it into a pixel-based algorithm. There is a challenge posed by the low echo signal-to-noise ratio (eSNR) when calculating beamformer contributions at pixels far away from the beam centreline. Together with the well-known scarcity of samples for covariance matrix estimation, this reduces the beamformer performance and degrades the image quality. To address this challenge, we implement the MVDR algorithm in two different ways. First, we develop the conventional minimum variance pixel-based (MVPB) beamformer that performs the MVDR after the pixel-based superposition step. This involves a combination of methods in the literature, extended over multiple transmits to increase the eSNR. Then we propose the coherent MVPB beamformer, where the MVDR is applied to data within individual transmits. Based on pressure field analysis, we develop new algorithms to improve the data alignment and matrix estimation, and hence overcome the low-eSNR issue. The methods are demonstrated on data acquired with an ultrasound open platform. The results show the coherent MVPB beamformer substantially outperforms the conventional MVPB in a series of experiments, including phantom and in vivo studies. Compared to the unified pixel-based beamformer, the newest delay-and-sum algorithm in [1], the coherent MVPB performs well on regions that conform to the diffuse scattering assumptions on which the minimum variance principles are based. It produces less good results for parts of the image that are dominated by specular reflections.

  11. Real-time monitoring of matrix metalloproteinase-9 collagenolytic activity with a surface plasmon resonance biosensor.

    PubMed

    Shoji, Atsushi; Kabeya, Mitsutaka; Sugawara, Masao

    2011-12-01

    We describe a simple method for real-time monitoring of matrix metalloproteinase-9 (MMP-9) collagenolytic activity for native triple helical collagen IV with a surface plasmon resonance (SPR) biosensor. The proteolytic activity of MMP-9 is measured as a decrease in the SPR signal resulting from the cleavage of collagen IV immobilized on the sensor surface. The kinetic parameters of full-length MMP-9 and its catalytic domain-catalytic constant (k(cat)), association rate constant (k(a)), and dissociation rate constant (k(d))-were estimated by the SPR method. The presence of sodium chloride and a nonionic detergent Brij-35 in a reaction solution led to the lower collagenolytic activity of MMP-9, whereas they suppressed the nonspecific interaction between MMP-9 and a cysteamine-modified chip. The comparison of kinetic parameters between MMP-9 and its catalytic domain revealed that the association constant of MMP-9 is much larger than that of the catalytic domain, suggesting that the interplay among hemopexin-like domain, fibronectin type II repeats motif, and linker region (O-glycosylated domain) plays an important role in recognizing collagen IV.

  12. 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

  13. 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.

  14. Mapping Electrical Crosstalk in Pixelated Sensor Arrays

    NASA Technical Reports Server (NTRS)

    Seshadri, Suresh (Inventor); Cole, David (Inventor); Smith, Roger M (Inventor); Hancock, Bruce R. (Inventor)

    2013-01-01

    The effects of inter pixel capacitance in a pixilated array may be measured by first resetting all pixels in the array to a first voltage, where a first image is read out, followed by resetting only a subset of pixels in the array to a second voltage, where a second image is read out, where the difference in the first and second images provide information about the inter pixel capacitance. Other embodiments are described and claimed.

  15. Mapping Electrical Crosstalk in Pixelated Sensor Arrays

    NASA Technical Reports Server (NTRS)

    Seshadri, Suresh (Inventor); Cole, David (Inventor); Smith, Roger M. (Inventor); Hancock, Bruce R. (Inventor)

    2017-01-01

    The effects of inter pixel capacitance in a pixilated array may be measured by first resetting all pixels in the array to a first voltage, where a first image is read out, followed by resetting only a subset of pixels in the array to a second voltage, where a second image is read out, where the difference in the first and second images provide information about the inter pixel capacitance. Other embodiments are described and claimed.

  16. A new ATLAS pixel front-end IC for upgraded LHC luminosity

    NASA Astrophysics Data System (ADS)

    Barbero, M.; Arutinov, D.; Beccherle, R.; Darbo, G.; Ely, R.; Fougeron, D.; Garcia-Sciveres, M.; Gnani, D.; Hemperek, T.; Karagounis, M.; Kluit, R.; Kostioukhine, V.; Mekkaoui, A.; Menouni, M.; Schipper, J.-D.

    2009-06-01

    A new pixel Front-End (FE) IC is being developed in a 130 nm technology for use in the upgraded ATLAS pixel detector. The new pixel FE will be made of smaller pixels (50×250 μm vs. 50×400 μm for the present FE, FE-I3), a much improved active area over inactive area ratio, and a new analog pixel chain tuned for low power and new detector input capacitance. The higher luminosity for which this IC is tuned implies a complete redefinition of the digital architecture logic, which will not be based on End-of-Column data buffering but on local pixel logic and local pixel data storage. An overview of the new FE is given with particular emphasis on the new digital logic architecture and possible architecture variations.

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

    PubMed Central

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

    2016-01-01

    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

  18. Matrix metalloproteinase-driven endochondral fracture union proceeds independently of osteoclast activity.

    PubMed

    McDonald, Michelle M; Morse, Alyson; Mikulec, Kathy; Peacock, Lauren; Baldock, Paul A; Kostenuik, Paul J; Little, David G

    2013-07-01

    As new insights into the complexities of endochondral fracture repair emerge, the temporal role of osteoclast activity remains ambiguous. With numerous antiresorptive agents available to treat bone disease, understanding their impact on bone repair is vital. Further, in light of recent work suggesting osteoclast activity may not be necessary during early endochondral fracture union, we hypothesize instead a pivotal role of matrix metalloproteinase (MMP) secreting cells in driving this process. Although the role of MMPs in fracture healing has been examined, no directly comparative experiments exist. We examined a number of antiresorptive treatments to either block osteoclast activity, including the potent bisphosphonates zoledronic acid (ZA) and clodronate (CLOD), which work via differing mechanisms, or antagonize osteoclastogenesis with recombinant OPG (HuOPG-Fc), comparing these directly to an inhibitor of MMP activity (MMI270). Endochondral ossification to union occurred normally in all antiresorptive groups. In contrast, MMP inhibition greatly impaired endochondral union, significantly delaying cartilage callus removal. MMP inhibition also produced smaller, denser hard calluses. Hard callus remodeling was, as expected, delayed with ZA, CLOD, and OPG treatment at 4 and 6 weeks, resulting in larger, more mineralized calluses at 6 weeks. As a result of reduced hard callus turnover, bone formation was reduced with antiresorptive agents at these time points. These results confirm that the achievement of endochondral fracture union occurs independently of osteoclast activity. Alternatively, MMP secretion by invading cells is obligatory to endochondral union. This study provides new insight into cellular contributions to bone repair and may abate concerns regarding antiresorptive therapies impeding initial fracture union.

  19. 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

  20. Pixel Analysis of Photospheric Spectral Data. I. Plasma Dynamics

    NASA Astrophysics Data System (ADS)

    Rasca, Anthony P.; Chen, James; Pevtsov, Alexei A.

    2016-11-01

    Recent observations of the photosphere using high spatial and temporal resolution show small dynamic features at or below the current resolving limits. A new pixel dynamics method has been developed to analyze spectral profiles and quantify changes in line displacement, width, asymmetry, and peakedness of photospheric absorption lines. The algorithm evaluates variations of line profile properties in each pixel and determines the statistics of such fluctuations averaged over all pixels in a given region. The method has been used to derive statistical characteristics of pixel fluctuations in observed quiet-Sun regions, an active region with no eruption, and an active region with an ongoing eruption. Using Stokes I images from the Vector Spectromagnetograph (VSM) of the Synoptic Optical Long-term Investigations of the Sun (SOLIS) telescope on 2012 March 13, variations in line width and peakedness of Fe i 6301.5 Å are shown to have a distinct spatial and temporal relationship with an M7.9 X-ray flare in NOAA 11429. This relationship is observed as stationary and contiguous patches of pixels adjacent to a sunspot exhibiting intense flattening in the line profile and line-center displacement as the X-ray flare approaches peak intensity, which is not present in area scans of the non-eruptive active region. The analysis of pixel dynamics allows one to extract quantitative information on differences in plasma dynamics on sub-pixel scales in these photospheric regions. The analysis can be extended to include the Stokes parameters and study signatures of vector components of magnetic fields and coupled plasma properties.

  1. Expression of matrix metalloproteinases during rat skin wound healing: evidence that membrane type-1 matrix metalloproteinase is a stromal activator of pro-gelatinase A.

    PubMed

    Okada, A; Tomasetto, C; Lutz, Y; Bellocq, J P; Rio, M C; Basset, P

    1997-04-07

    Skin wound healing depends on cell migration and extracellular matrix remodeling. Both processes, which are necessary for reepithelization and restoration of the underlying connective tissue, are believed to involve the action of extracellular proteinases. We screened cDNA libraries and we found that six matrix metalloproteinase genes were highly expressed during rat skin wound healing. They were namely those of stromelysin 1, stromelysin 3, collagenase 3, gelatinase A (GelA), gelatinase B, and membrane type-1 matrix metalloproteinase (MT1-MMP). The expression kinetics of these MMP genes, the tissue distribution of their transcripts, the results of cotransfection experiments in COS-1 cells, and zymographic analyses performed using microdissected rat wound tissues support the possibility that during cutaneous wound healing pro-GelA and pro-gelatinase B are activated by MT1-MMP and stromelysin 1, respectively. Since MT1-MMP has been demonstrated to be a membrane-associated protein (Sato, H., T. Takino, Y. Okada, J. Cao, A. Shinagawa, E. Yamamoto, and M. Seiki. 1994. Nature (Lond.). 370: 61-65), our finding that GelA and MT1-MMP transcripts were expressed in stromal cells exhibiting a similar tissue distribution suggests that MT1-MMP activates pro-GelA at the stromal cell surface. This possibility is further supported by our observation that the processing of pro-GelA to its mature form correlated to the detection of MT1-MMP in cell membranes of rat fibroblasts expressing the MT1-MMP and GelA genes. These observations, together with the detection of high levels of the mature GelA form in the granulation tissue but not in the regenerating epidermis, suggest that MT1-MMP and GelA contribute to the restoration of connective tissue during rat skin wound healing.

  2. SVGA and XGA active matrix microdisplays for head-mounted applications

    NASA Astrophysics Data System (ADS)

    Alvelda, Phillip; Bolotski, Michael; Brown, Imani L.

    2000-03-01

    The MicroDisplay Corporation's liquid crystal on silicon (LCOS) display devices are based on the union of several technologies with the extreme integration capability of conventionally fabricated CMOS substrates. The fast liquid crystal operation modes and new scalable high-performance pixel addressing architectures presented in this paper enable substantially improved color, contrast, and brightness while still satisfying the optical, packaging, and power requirements of portable applications. The entire suite of MicroDisplay's technologies was devised to create a line of mixed-signal application-specific integrated circuits (ASICs) in single-chip display systems. Mixed-signal circuits can integrate computing, memory, and communication circuitry on the same substrate as the display drivers and pixel array for a multifunctional complete system-on-a-chip. System-on-a-chip benefits also include reduced head supported weight requirements through the elimination of off-chip drive electronics.

  3. 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

  4. 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

  5. Cellular aspartyl proteases promote the unconventional secretion of biologically active HIV-1 matrix protein p17

    PubMed Central

    Caccuri, Francesca; Iaria, Maria Luisa; Campilongo, Federica; Varney, Kristen; Rossi, Alessandro; Mitola, Stefania; Schiarea, Silvia; Bugatti, Antonella; Mazzuca, Pietro; Giagulli, Cinzia; Fiorentini, Simona; Lu, Wuyuan; Salmona, Mario; Caruso, Arnaldo

    2016-01-01

    The human immune deficiency virus type 1 (HIV-1) matrix protein p17 (p17), although devoid of a signal sequence, is released by infected cells and detected in blood and in different organs and tissues even in HIV-1-infected patients undergoing successful combined antiretroviral therapy (cART). Extracellularly, p17 deregulates the function of different cells involved in AIDS pathogenesis. The mechanism of p17 secretion, particularly during HIV-1 latency, still remains to be elucidated. A recent study showed that HIV-1-infected cells can produce Gag without spreading infection in a model of viral latency. Here we show that in Gag-expressing cells, secretion of biologically active p17 takes place at the plasma membrane and occurs following its interaction with phosphatidylinositol-(4,5)-bisphosphate and its subsequent cleavage from the precursor Gag (Pr55Gag) operated by cellular aspartyl proteases. These enzymes operate a more complex Gag polypeptide proteolysis than the HIV-1 protease, thus hypothetically generating slightly truncated or elongated p17s in their C-terminus. A 17 C-terminal residues excised p17 was found to be structurally and functionally identical to the full-length p17 demonstrating that the final C-terminal region of p17 is irrelevant for the protein’s biological activity. These findings offer new opportunities to identify treatment strategies for inhibiting p17 release in the extracellular microenvironment. PMID:27905556

  6. Cell-mediated degradation of type IV collagen and gelatin films is dependent on the activation of matrix metalloproteinases.

    PubMed Central

    Atkinson, S J; Ward, R V; Reynolds, J J; Murphy, G

    1992-01-01

    The ability of normal rabbit dermal fibroblasts to degrade films of type IV collagen and gelatin when stimulated by phorbol ester was shown to be dependent on the induction, secretion and activation of 95 kDa gelatinase B and the secretion and activation of 72 kDa gelatinase A and stromelysin. Degradation was inhibited by exogenous human recombinant tissue inhibitor of metalloproteinases-1, specific antibodies to gelatinase and stromelysin and by the reactive-oxygen-metabolite inhibitor catalase. We discuss the various pathways for activation of matrix metalloproteinases in this model system and conclude that, although plasmin may play a key role in the activation of gelatinase B and stromelysin, gelatinase A is activated by a mechanism which has yet to be elucidated. The involvement of oxygen radicals in the direct activation of matrix metalloproteinases in this model is thought to be unlikely. Images Fig. 2. Fig. 3. Fig. 4. PMID:1463464

  7. 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.

  8. 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.

  9. Making a trillion pixels dance

    NASA Astrophysics Data System (ADS)

    Singh, Vivek; Hu, Bin; Toh, Kenny; Bollepalli, Srinivas; Wagner, Stephan; Borodovsky, Yan

    2008-03-01

    In June 2007, Intel announced a new pixelated mask technology. This technology was created to address the problem caused by the growing gap between the lithography wavelength and the feature sizes patterned with it. As this gap has increased, the quality of the image has deteriorated. About a decade ago, Optical Proximity Correction (OPC) was introduced to bridge this gap, but as this gap continued to increase, one could not rely on the same basic set of techniques to maintain image quality. The computational lithography group at Intel sought to alleviate this problem by experimenting with additional degrees of freedom within the mask. This paper describes the resulting pixelated mask technology, and some of the computational methods used to create it. The first key element of this technology is a thick mask model. We realized very early in the development that, unlike traditional OPC methods, the pixelated mask would require a very accurate thick mask model. Whereas in the traditional methods, one can use the relatively coarse approximations such as the boundary layer method, use of such techniques resulted not just in incorrect sizing of parts of the pattern, but in whole features missing. We built on top of previously published domain decomposition methods, and incorporated limitations of the mask manufacturing process, to create an accurate thick mask model. Several additional computational techniques were invoked to substantially increase the speed of this method to a point that it was feasible for full chip tapeout. A second key element of the computational scheme was the comprehension of mask manufacturability, including the vital issue of the number of colors in the mask. While it is obvious that use of three or more colors will give the best image, one has to be practical about projecting mask manufacturing capabilities for such a complex mask. To circumvent this serious issue, we eventually settled on a two color mask - comprising plain glass and etched

  10. Sync Matrix

    SciTech Connect

    Metz, William C.; Metz, W. Chris; Mitrani, Jacques E.; Hewett, Jr., Paul L.; Jones, Christopher A.

    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.

  11. Large monolithic particle pixel-detector in high-voltage CMOS technology

    NASA Astrophysics Data System (ADS)

    Perić, I.; Takacs, C.

    2010-12-01

    A large monolithic particle pixel-detector implemented as system on a chip in a high-voltage 0.35 μm CMOS technology will be presented. The detector uses high-voltage n-well/p-substrate diodes as pixel-sensors. The diodes can be reversely biased with more than 60 V. In this way, depleted zones of about 10 μm thickness are formed, where the signal charges can be collected by drift. Due to fast charge collection in the strong electric-field zones, a higher radiation tolerance of the sensor is expected than in the case of the standard MAPS detectors. Simple pixel-readout electronics are implemented inside the n-wells. The readout is based on a source follower with one select- and two reset-transistors. Due to embedding of the pixel-readout electronics inside the collecting electrodes (n-wells) there are no insensitive zones within the pixel matrix. The detector chip contains a 128×128 matrix consisting of pixels of 21×21 μm2 -size. The diode voltages of one selected pixel-row are received at the bottom of the matrix by 128 eight-bit single-slope ADCs. All ADCs operate in parallel. The ADC codes are read out using eight LVDS 500 MBit/s output links. The readout electronics are designed to allow the readout of the whole pixel matrix in less than 50 μs. The total DC power consumption of the chip is 50 mW. All analog parts of the chip are implemented using radiation-hard layout techniques. Experimental results will be presented.

  12. Design and TCAD simulation of planar p-on-n active-edge pixel sensors for the next generation of FELs

    NASA Astrophysics Data System (ADS)

    Dalla Betta, G.-F.; Batignani, G.; Benkechkache, M. A.; Bettarini, S.; Casarosa, G.; Comotti, D.; Fabris, L.; Forti, F.; Grassi, M.; Latreche, S.; Lodola, L.; Malcovati, P.; Manghisoni, M.; Mendicino, R.; Morsani, F.; Paladino, A.; Pancheri, L.; Paoloni, E.; Ratti, L.; Re, V.; Rizzo, G.; Traversi, G.; Vacchi, C.; Verzellesi, G.; Xu, H.

    2016-07-01

    We report on the design and TCAD simulations of planar p-on-n sensors with active edge aimed at a four-side buttable X-ray detector module for future FEL applications. Edge terminations with different number of guard rings were designed to find the best trade-off between breakdown voltage and border gap size. The methodology of the sensor design, the optimization of the most relevant parameters to maximize the breakdown voltage and the final layout are described.

  13. 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.

  14. Modulation of CD147-induced matrix metalloproteinase activity: role of CD147 N-glycosylation.

    PubMed

    Huang, Wan; Luo, Wen-Juan; Zhu, Ping; Tang, Juan; Yu, Xiao-Ling; Cui, Hong-Yong; Wang, Bin; Zhang, Yang; Jiang, Jian-Li; Chen, Zhi-Nan

    2013-01-15

    Degradation of the basement membrane by MMPs (matrix metalloproteinases) is one of the most critical steps in tumour progression. CD147 is a tumour-associated antigen that plays a key regulatory role for MMP activities. In the present study, mass spectrum analysis demonstrated that the purified native CD147 from human lung cancer tissue was N-glycosylated and contained a series of high-mannose and complex-type N-linked glycan structures. Moreover, native glycosylated CD147 existed exclusively as oligomers in solution and directly stimulated MMP production more efficiently than non-glycosylated prokaryotic CD147. The glycosylation site mutation results indicated that, among three N-glycan attachment sites, the N152Q mutants were retained in the endoplasmic reticulum and unfolded protein response signalling was activated. This improper intracellular accumulation impaired its MMP-inducing activity. Increased β1,6-branching of N-glycans as a result of overexpression of GnT-V (N-acetylglucosaminyltransferase V) plays an important role in tumour metastasis. In the present study, we identified CD147 as a target protein of GnT-V and found that overexpression of GnT-V resulted in an elevated level of CD147 at the plasma membrane and in cell-conditioned medium, thereby increasing the induction of MMPs. The present study reveals the important role of N-glycosylation of CD147 in its biological function and implied that targeting aberrant β1,6-branching of N-glycans on CD147 would be valuable for the development of novel therapeutic modalities against carcinoma.

  15. Matrix immobilization enhances the tissue repair activity of growth factor gene therapy vectors.

    PubMed

    Doukas, J; Chandler, L A; Gonzalez, A M; Gu, D; Hoganson, D K; Ma, C; Nguyen, T; Printz, M A; Nesbit, M; Herlyn, M; Crombleholme, T M; Aukerman, S L; Sosnowski, B A; Pierce, G F

    2001-05-01

    Although growth factor proteins display potent tissue repair activities, difficulty in sustaining localized therapeutic concentrations limits their therapeutic activity. We reasoned that enhanced histogenesis might be achieved by combining growth factor genes with biocompatible matrices capable of immobilizing vectors at delivery sites. When delivered to subcutaneously implanted sponges, a platelet-derived growth factor B-encoding adenovirus (AdPDGF-B) formulated in a collagen matrix enhanced granulation tissue deposition 3- to 4-fold (p < or = 0.0002), whereas vectors encoding fibroblast growth factor 2 or vascular endothelial growth factor promoted primarily angiogenic responses. By day 8 posttreatment of ischemic excisional wounds, collagen-formulated AdPDGF-B enhanced granulation tissue and epithelial areas up to 13- and 6-fold (p < 0.009), respectively, and wound closure up to 2-fold (p < 0.05). At longer times, complete healing without excessive scar formation was achieved. Collagen matrices were shown to retain both vector and transgene products within delivery sites, enabling the transduction and stimulation of infiltrating repair cells. Quantitative PCR and RT-PCR demonstrated both vector DNA and transgene mRNA within wound beds as late as 28 days posttreatment. By contrast, aqueous formulations allowed vector seepage from application sites, leading to PDGF-induced hyperplasia in surrounding tissues but not wound beds. Finally, repeated applications of PDGF-BB protein were required for neotissue induction approaching equivalence to a single application of collagen-immobilized AdPDGF-B, confirming the utility of this gene transfer approach. Overall, these studies demonstrate that immobilizing matrices enable the controlled delivery and activity of tissue promoting genes for the effective regeneration of injured tissues.

  16. First results from electrical qualification measurements on DEPFET pixel detector

    NASA Astrophysics Data System (ADS)

    Majewski, Petra; Andricek, Ladislav; Lauf, Thomas; Lechner, Peter; Lutz, Gerhard; Reiffers, Jonas; Richter, Rainer; Schaller, Gerhard; Schnecke, Martina; Schopper, Florian; Soltau, Heike; Stefanescu, Alexander; Strüder, Lothar; Treis, Johannes

    2010-07-01

    We report on the first results from a new setup for electrical qualification measurements of DEPFET pixel detector matrices. In order to measure the transistor properties of all pixels, the DEPFET device is placed into a benchtest setup and electrically contacted via a probecard. Using a switch matrix, each pixel of the detector array can be addressed individually for characterization. These measurements facilitate to pre-select the best DEPFET matrices as detector device prior to the mounting of the matrix and allow to investigate topics like the homogeneity of transistor parameters on device, wafer and batch level in order to learn about the stability and reproducibility of the production process. Especially with regard to the detector development for the IXO Wide Field Imager (WFI), this yield learning will be an important tool. The first electrical qualification measurements with this setup were done on DEPFET macropixel detector flight hardware, which will form the FPAs of the Mercury Imaging X-ray Spectrometer (MIXS) on board of the 5th ESA cornerstone mission BepiColombo. The DEPFET array consists of 64×64 macropixel for which the transfer, output and clear characteristics were measured.

  17. Phenotypic differences in matrix metalloproteinase 2 activity between fibroblasts from 3 bovine muscles.

    PubMed

    Archile-Contreras, A C; Mandell, I B; Purslow, P P

    2010-12-01

    Different muscles in a beef carcass are known to respond differently to the same stimulus or animal growth pattern or both. This may complicate the search by the meat industry for production methods to render meat tender. One of the major differences between muscles in the same carcass is in the expression of intramuscular connective tissue. Current study investigates the existence of a phenotypic difference among fibroblasts from 3 bovine skeletal muscles as exemplified by the expression of matrix metalloproteinases (MMP) the main enzymes responsible for connective tissue turnover. The sensitivity of phenotypic differences to cell culture conditions (passage number, presence of growth factors from fetal serum) was also examined. Fibroblasts, the main cells responsible for the production and turnover of collagen were isolated from LM, semitendinosus (STN), and sternomandibularis (SMD) muscles from a bull calf and grown in DMEM, 10% fetal bovine serum, and 5% CO(2). Cell doubling times, survival time, resting expression, and activity of MMP and the effect of serum withdrawal in the culture media on MMP expression and activity were determined for each cell line during 15 passages. Fibroblasts isolated from the 3 muscles had different growth potentials. The shortest (P < 0.0001) cell doubling times for almost every passage were found in cells from STN muscle. Cells from the LM had a shorter (P < 0.0001) survival time in comparison with STN and SMD. Cells derived from the STN had greater values (P > 0.05) of MMP-2 activity in comparison with LM and SMD cells until passage 4. At passage 15, no activity was detected for any cell line. Serum withdrawal generally reduced MMP-2 activation but did not eliminate differences in activity between fibroblasts from the 3 muscles. These results suggest that fibroblasts from different locations are phenotypically different and may respond differently to the same growth or nutritional stimulus in vitro. This may be related to in vivo

  18. Vitamin D Inhibits Expression and Activity of Matrix Metalloproteinase in Human Lung Fibroblasts (HFL-1) Cells

    PubMed Central

    Kim, Seo Hwa; Baek, Moon Seong; Yoon, Dong Sik; Park, Jong Seol; Yoon, Byoung Wook; Oh, Byoung Su; Park, Jinkyeong

    2014-01-01

    Background Low levels of serum vitamin D is associated with several lung diseases. The production and activation of matrix metalloproteinases (MMPs) may play an important role in the pathogenesis of emphysema. The aim of the current study therefore is to investigate if vitamin D modulates the expression and activation of MMP-2 and MMP-9 in human lung fibroblasts (HFL-1) cells. Methods HFL-1 cells were cast into three-dimensional collagen gels and stimulated with or without interleukin-1β (IL-1β) in the presence or absence of 100 nM 25-hydroxyvitamin D (25(OH)D) or 1,25-dihydroxyvitamin D (1,25(OH)2D) for 48 hours. Trypsin was then added into the culture medium in order to activate MMPs. To investigate the activity of MMP-2 and MMP-9, gelatin zymography was performed. The expression of the tissue inhibitor of metalloproteinase (TIMP-1, TIMP-2) was measured by enzyme-linked immunosorbent assay. Expression of MMP-9 mRNA and TIMP-1, TIMP-2 mRNA was quantified by real time reverse transcription polymerase chain reaction. Results IL-1β significantly stimulated MMP-9 production and mRNA expression. Trypsin converted latent MMP-2 and MMP-9 into their active forms of MMP-2 (66 kDa) and MMP-9 (82 kDa) within 24 hours. This conversion was significantly inhibited by 25(OH)D (100 nM) and 1,25(OH)2D (100 nM). The expression of MMP-9 mRNA was also significantly inhibited by 25(OH)D and 1,25(OH)2D. Conclusion Vitamin D, 25(OH)D, and 1,25(OH)2D play a role in regulating human lung fibroblast functions in wound repair and tissue remodeling through not only inhibiting IL-1β stimulated MMP-9 production and conversion to its active form but also inhibiting IL-1β inhibition on TIMP-1 and TIMP-2 production. PMID:25237378

  19. Silicon pixel R&D for CLIC

    NASA Astrophysics Data System (ADS)

    Munker, M.

    2017-01-01

    Challenging detector requirements are imposed by the physics goals at the future multi-TeV e+ e‑ Compact Linear Collider (CLIC). A single point resolution of 3 μm for the vertex detector and 7 μm for the tracker is required. Moreover, the CLIC vertex detector and tracker need to be extremely light weighted with a material budget of 0.2% X0 per layer in the vertex detector and 1–2% X0 in the tracker. A fast time slicing of 10 ns is further required to suppress background from beam-beam interactions. A wide range of sensor and readout ASIC technologies are investigated within the CLIC silicon pixel R&D effort. Various hybrid planar sensor assemblies with a pixel size of 25×25 μm2 and 55×55 μm2 have been produced and characterised by laboratory measurements and during test-beam campaigns. Experimental and simulation results for thin (50 μm–500 μm) slim edge and active-edge planar, and High-Voltage CMOS sensors hybridised to various readout ASICs (Timepix, Timepix3, CLICpix) are presented.

  20. 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.

  1. Full-order Mueller matrix polarimeter using liquid-crystal phase retarders and active illumination

    NASA Astrophysics Data System (ADS)

    Dayton, David C.; Hoover, Brian G.; Gonglewski, John D.

    2003-03-01

    Full order Stokes polarimeters are often composed of an analyzer consisting of a rotating quarter wave plate in front of a horizontal polarizer. A number of measurements are then made with the wave-plate oriented at different angle. The four-element Stokes vector is then computed from a linear combination of these measurements. A disadvantage of this device is that only a limited range of analyzer states can be generated. As a result a large number of measurements may be required to reduce the noise gain in the Stokes vector reconstructor. In this paper we describe a polarimeter based on a linear polarizer and two variable wave plates. It can be shown that such a device can produce an arbitrary polarization state. An active polarimeter consists of a generator stage, which transmits a laser illuminator with different polarization states and a receiver with a polarization analyzer stage. In our system both generator and analyzer stages consist of a horizontal polarizer and two variable wave-plates. A sixteen element Mueller matrix of resolved images is then formed for target characterization.

  2. 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.

  3. Development activities of a CdTe/CdZnTe pixel detector for gamma-ray spectrometry with imaging and polarimetry capability in astrophysics

    NASA Astrophysics Data System (ADS)

    Gálvez, J. L.; Hernanz, M.; Álvarez, J. M.; Álvarez, L.; La Torre, M.; Caroli, E.; Lozano, M.; Pellegrini, G.; Ullán, M.; Cabruja, E.; Martínez, R.; Chmeissani, M.; Puigdengoles, C.

    2013-05-01

    In the last few years we have been working on feasibility studies of future instruments in the gamma-ray range, from several keV up to a few MeV, in collaboration with other research institutes. High sensitivities are essential to perform detailed studies of cosmic explosions and cosmic accelerators, e.g., Supernovae, Classical Novae, Supernova Remnants (SNRs), Gamma-Ray Bursts (GRBs), Pulsars, Active Galactic Nuclei (AGN).Cadmium Telluride (CdTe) and Cadmium Zinc Telluride (CdZnTe) are very attractive materials for gamma-ray detection, since they have already demonstrated their great performance onboard current space missions, such as IBIS/INTEGRAL and BAT/SWIFT, and future projects like ASIM onboard the ISS. However, the energy coverage of these instruments is limited up to a few hundred keV, and there has not been yet a dedicated instrument for polarimetry.Our research and development activities aim to study a gamma-ray imaging spectrometer in the MeV range based on CdTe detectors, suited either for the focal plane of a focusing mission or as a calorimeter for a Compton camera. In addition, our undergoing detector design is proposed as the baseline for the payload of a balloon-borne experiment dedicated to hard X- and soft gamma-ray polarimetry, currently under study and called CμSP (CZT μ-Spectrometer Polarimeter). Other research institutes such as INAF-IASF, DTU Space, LIP, INEM/CNR, CEA, are involved in this proposal. We will report on the main features of the prototype we are developing at the Institute of Space Sciences, a gamma-ray detector with imaging and polarimetry capabilities in order to fulfil the combined requirement of high detection efficiency with good spatial and energy resolution driven by the science.

  4. Proceedings of PIXEL98 -- International pixel detector workshop

    SciTech Connect

    Anderson, D.F.; Kwan, S.

    1998-08-01

    Experiments around the globe face new challenges of more precision in the face of higher interaction rates, greater track densities, and higher radiation doses, as they look for rarer and rarer processes, leading many to incorporate pixelated solid-state detectors into their plans. The highest-readout rate devices require new technologies for implementation. This workshop reviewed recent, significant progress in meeting these technical challenges. Participants presented many new results; many of them from the weeks--even days--just before the workshop. Brand new at this workshop were results on cryogenic operation of radiation-damaged silicon detectors (dubbed the Lazarus effect). Other new work included a diamond sensor with 280-micron collection distance; new results on breakdown in p-type silicon detectors; testing of the latest versions of read-out chip and interconnection designs; and the radiation hardness of deep-submicron processes.

  5. Serial Pixel Analog-to-Digital Converter

    SciTech Connect

    Larson, E D

    2010-02-01

    This method reduces the data path from the counter to the pixel register of the analog-to-digital converter (ADC) from as many as 10 bits to a single bit. The reduction in data path width is accomplished by using a coded serial data stream similar to a pseudo random number (PRN) generator. The resulting encoded pixel data is then decoded into a standard hexadecimal format before storage. The high-speed serial pixel ADC concept is based on the single-slope integrating pixel ADC architecture. Previous work has described a massively parallel pixel readout of a similar architecture. The serial ADC connection is similar to the state-of-the art method with the exception that the pixel ADC register is a shift register and the data path is a single bit. A state-of-the-art individual-pixel ADC uses a single-slope charge integration converter architecture with integral registers and “one-hot” counters. This implies that parallel data bits are routed among the counter and the individual on-chip pixel ADC registers. The data path bit-width to the pixel is therefore equivalent to the pixel ADC bit resolution.

  6. EGF AND TGF-{alpha} motogenic activities are mediated by the EGF receptor via distinct matrix-dependent mechanisms

    SciTech Connect

    Ellis, Ian R.; Schor, Ana M.; Schor, Seth L. . E-mail: s.l.schor@dundee.ac.uk

    2007-02-15

    EGF and TGF-{alpha} induce an equipotent stimulation of fibroblast migration and proliferation. In spite of their homologous structure and ligation by the same receptor (EGFR), we report that their respective motogenic activities are mediated by different signal transduction intermediates, with p70{sup S6K} participating in EGF signalling and phospholipase C{gamma} in TGF-{alpha} signalling. We additionally demonstrate that EGF and TGF-{alpha} motogenic activities may be resolved into two stages: (a) cell 'activation' by a transient exposure to either cytokine, and (b) the subsequent 'manifestation' of an enhanced migratory phenotype in the absence of cytokine. The cell activation and manifestation stages for each cytokine are mediated by distinct matrix-dependent mechanisms: motogenetic activation by EGF requires the concomitant functionality of EGFR and the hyaluronan receptor CD44, whereas activation by TGF-{alpha} requires EGFR and integrin {alpha}v{beta}3. Manifestation of elevated migration no longer requires the continued presence of exogenous cytokine and functional EGFR but does require the above mentioned matrix receptors, as well as their respective ligands, i.e., hyaluronan in the case of EGF, and vitronectin in the case of TGF-{alpha}. In contrast, the mitogenic activities of EGF and TGF-{alpha} are independent of CD44 and {alpha}v{beta}3 functionality. These results demonstrate clear qualitative differences between EGF and TGF-{alpha} pathways and highlight the importance of the extracellular matrix in regulating cytokine bioactivity.

  7. 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

  8. Captopril and lisinopril only inhibit matrix metalloproteinase-2 (MMP-2) activity at millimolar concentrations.

    PubMed

    Kuntze, Luciana B; Antonio, Raquel C; Izidoro-Toledo, Tatiane C; Meschiari, Cesar A; Tanus-Santos, Jose E; Gerlach, Raquel F

    2014-03-01

    Matrix metalloproteinase-2 (MMP-2) shares structural similarities with the angiotensin-converting enzyme (ACE). ACE inhibitors have been described to inhibit MMP-2, but this inhibitory potential was not shown using a highly purified MMP-2. This study aimed to investigate the inhibitory potential of captopril and lisinopril regarding MMP-2 activity. The first objective was to test the potential of captopril to change the pH of the buffer solution. The second objective was to test the direct inhibitory effect of captopril and lisinopril on plasma MMP-2 and on recombinant human MMP-2 (rhMMP-2). The in vitro activity assays included gelatin zymography and a fluorimetric assay. Captopril solubilization significantly decreased the pH of the 50 mM Tris buffer solution at the following concentrations: 2 mM (p < 0.05), 4 mM and 8 mM (p < 0.01), while only the 8 mM lisinopril induced a drop in pH (p < 0.05). Thus, only 200 mM buffer solutions were used. Zymography results of plasma MMP-2 and rhMMP-2 showed that inhibition only happened at captopril concentrations ≥ 4 and 1 mM, respectively (p < 0.05), while only the higher concentration of lisinopril (8 mM) inhibited plasma MMP-2 (p < 0.05). In the fluorimetric assay, captopril led to significant inhibition of the rhMMP-2 activity at concentrations ≥2 mM (p < 0.01), whereas aminophenylmercuric acetate-activated rhMMP-2 was inhibited by 0.5 mM captopril (p < 0.01). The captopril and lisinopril concentrations found to inhibit MMP-2 are 3 orders of magnitude higher than those present in vivo after drug administration. We also discuss possible pitfalls for gelatinase inhibitory assays (besides the obvious pH problem already cited). In conclusion, this study's data show that captopril and lisinopril did not inhibit MMP-2 directly at the concentrations reached in vivo.

  9. Matrix Vesicle Enzyme Activity and Phospholipid Content in Endosteal Bone Following Implantation of Osseointegrating and Non-Osseointegrating Implant Materials.

    DTIC Science & Technology

    1992-01-01

    vesicles are an initial locus for calcification in most calcified matrices. b. The studies to be performed include: alkaline phosphatase specific activity...Treatment and Contralateral Tibias .............................. 23 Figure 6. Alkaline Phosphatase Specific Activity of Matrix Vesicle-Enriched Membranes...endosteal tissue removed from treated tibias, as well as the contralateral control. There was an increase at six days in MVEM alkaline phosphatase and

  10. Fabrication and performance of mercuric iodide pixellated detectors

    NASA Astrophysics Data System (ADS)

    van den Berg, Lodewijk; Bastian, Lloyd F.; Zhang, Feng; Lenos, Howard; Capote, M. Albert

    2007-09-01

    The radiation detection efficiency and spectral resolution of mercuric iodide detectors can be improved significantly by increasing the volume of the detectors and by using a pixellated anode structure. Detector bodies with a thickness of nominally 10 mm and an active area of approximately 14 mm x 14 mm have been used for these experiments. The detectors were cut from single crystals grown by the physical vapor transport method. The cut surfaces were polished and etched using a string saw and potassium iodide solutions. The Palladium contacts were deposited by magnetron sputtering through stainless steel masks. The cathode contact is continuous; the anode contacts consist of an array of 11 x 11 pixels surrounded by a guard ring. The resistance between a pixel and its surrounding contacts should be larger than 0.25 Gohm. The detector is mounted on a substrate that makes it possible to connect the anode pixels to an ASIC, and is conditioned so that it is stable for all pixels at a bias of -3000 Volts. Under these conditions the spectral resolution for Cs-137 gamma rays (662 keV) is approximately 5% FWHM. When depth sensing correction methods are applied, the resolution improves to about 2% FWHM or better. It is expected that the performance of the devices can be improved by the careful selection of crystal parts that are free of structural defects. Details of the fabrication technologies will be described. The effects of material inhomogeneities and transport properties of the charge carriers will be discussed.

  11. Infrared astronomy - Pixels to spare

    SciTech Connect

    Mccaughrean, M. )

    1991-07-01

    An infrared CCD camera containing an array with 311,040 pixels arranged in 486 rows of 640 each is tested. The array is a chip of platinum silicide (PtSi), sensitive to photons with wavelengths between 1 and 6 microns. Observations of the Hubble Space Telescope, Mars, Pluto and moon are reported. It is noted that the satellite's twin solar-cell arrays, at an apparent separation of about 1 1/4 arc second, are well resolved. Some two dozen video frames were stacked to make each presented image of Mars at 1.6 microns; at this wavelength Mars appears much as it does in visible light. A stack of 11 images at a wavelength of 1.6 microns is used for an image of Jupiter with its Great Red Spot and moons Io and Europa.

  12. Dead pixel replacement in LWIR microgrid polarimeters.

    PubMed

    Ratliff, Bradley M; Tyo, J Scott; Boger, James K; Black, Wiley T; Bowers, David L; Fetrow, Matthew P

    2007-06-11

    LWIR imaging arrays are often affected by nonresponsive pixels, or "dead pixels." These dead pixels can severely degrade the quality of imagery and often have to be replaced before subsequent image processing and display of the imagery data. For LWIR arrays that are integrated with arrays of micropolarizers, the problem of dead pixels is amplified. Conventional dead pixel replacement (DPR) strategies cannot be employed since neighboring pixels are of different polarizations. In this paper we present two DPR schemes. The first is a modified nearest-neighbor replacement method. The second is a method based on redundancy in the polarization measurements.We find that the redundancy-based DPR scheme provides an order-of-magnitude better performance for typical LWIR polarimetric data.

  13. Active matrix organic light emitting diode (AMOLED) performance and life test results

    NASA Astrophysics Data System (ADS)

    Fellowes, David A.; Botkin, Michael E.; Draper, Russell S.; Coletta, Jason

    2013-05-01

    The U.S. Army and eMagin Corporation established a Cooperative Research and Development Agreement (CRADA) to characterize the ongoing improvements in the lifetime of OLED displays. This CRADA also called for the evaluation of OLED performance as the need arises, especially when new products are developed or when a previously untested parameter needs to be understood. In 2006, eMagin Corporation developed long-life OLED-XL devices for use in their AMOLED microdisplays for head-worn applications. Through Research and Development programs from 2007 to 2012 with the U.S. Government, eMagin made additional improvements in OLED life and developed the first SXGA (1280 X 1024 with triad pixels) and WUXGA (1920 X 1200 with triad pixels) OLED microdisplays. US Army RDECOM CERDEC NVESD conducted life and performance tests on these displays, publishing results at the 2012, 2011, 2010, 2009, 2008, and 2007 SPIE Defense, Security and Sensing Symposia. Life and performance tests have continued through 2013, and this data will be presented along with a comparison to 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 desirable.

  14. SLHC upgrade plans for the ATLAS pixel detector

    NASA Astrophysics Data System (ADS)

    Šícho, Petr

    2009-08-01

    The ATLAS pixel detector is an 80 million channels silicon tracking system designed to detect charged tracks and secondary vertices with very high precision. An upgrade of the ATLAS pixel detector is presently being considered, enabling to cope with higher luminosity at Super Large Hadron Collider (SLHC). The increased luminosity leads to extremely high radiation doses in the innermost region of the ATLAS tracker. Options considered for a new detector are discussed, as well as some important R&D activities, such as investigations towards novel detector geometries and novel processes.

  15. Method for fabricating pixelated silicon device cells

    SciTech Connect

    Nielson, Gregory N.; Okandan, Murat; Cruz-Campa, Jose Luis; Nelson, Jeffrey S.; Anderson, Benjamin John

    2015-08-18

    A method, apparatus and system for flexible, ultra-thin, and high efficiency pixelated silicon or other semiconductor photovoltaic solar cell array fabrication is disclosed. A structure and method of creation for a pixelated silicon or other semiconductor photovoltaic solar cell array with interconnects is described using a manufacturing method that is simplified compared to previous versions of pixelated silicon photovoltaic cells that require more microfabrication steps.

  16. The Phase-1 upgrade of the CMS pixel detector

    NASA Astrophysics Data System (ADS)

    Klein, Katja

    2017-02-01

    The CMS experiment features a pixel detector with three barrel layers and two discs per side, corresponding to an active silicon area of 1 m2. The detector delivered high-quality data during LHC Run 1. However, the CMS pixel detector was designed for the nominal instantaneous LHC luminosity of 1 ·1034cm-2s-1 . It is expected that the instantaneous luminosity will increase and reach twice the design value before Long Shutdown 3, scheduled for 2023. Under such conditions, the present readout chip would suffer from data loss due to buffer overflow, leading to significant inefficiencies of up to 16%. The CMS collaboration is presently constructing a new pixel detector to replace the present device during the winter shutdown 2016/2017. The design of this new detector will be outlined, the construction status summarized and the performance described.

  17. Virus based Full Colour Pixels using a Microheater

    PubMed Central

    Kim, Won-Geun; Kim, Kyujung; Ha, Sung-Hun; Song, Hyerin; Yu, Hyun-Woo; Kim, Chuntae; Kim, Jong-Man; Oh, Jin-Woo

    2015-01-01

    Mimicking natural structures has been received considerable attentions, and there have been a few practical advances. Tremendous efforts based on a self-assembly technique have been contributed to the development of the novel photonic structures which are mimicking nature’s inventions. We emulate the photonic structures from an origin of colour generation of mammalian skins and avian skin/feathers using M13 phage. The structures can be generated a full range of RGB colours that can be sensitively switched by temperature and substrate materials. Consequently, we developed an M13 phage-based temperature-dependent actively controllable colour pixels platform on a microheater chip. Given the simplicity of the fabrication process, the low voltage requirements and cycling stability, the virus colour pixels enable us to substitute for conventional colour pixels for the development of various implantable, wearable and flexible devices in future. PMID:26334322

  18. Virus based Full Colour Pixels using a Microheater

    NASA Astrophysics Data System (ADS)

    Kim, Won-Geun; Kim, Kyujung; Ha, Sung-Hun; Song, Hyerin; Yu, Hyun-Woo; Kim, Chuntae; Kim, Jong-Man; Oh, Jin-Woo

    2015-09-01

    Mimicking natural structures has been received considerable attentions, and there have been a few practical advances. Tremendous efforts based on a self-assembly technique have been contributed to the development of the novel photonic structures which are mimicking nature’s inventions. We emulate the photonic structures from an origin of colour generation of mammalian skins and avian skin/feathers using M13 phage. The structures can be generated a full range of RGB colours that can be sensitively switched by temperature and substrate materials. Consequently, we developed an M13 phage-based temperature-dependent actively controllable colour pixels platform on a microheater chip. Given the simplicity of the fabrication process, the low voltage requirements and cycling stability, the virus colour pixels enable us to substitute for conventional colour pixels for the development of various implantable, wearable and flexible devices in future.

  19. Operational experience with the ALICE pixel detector

    NASA Astrophysics Data System (ADS)

    Mastroserio, A.

    2017-01-01

    The Silicon Pixel Detector (SPD) constitutes the two innermost layers of the Inner Tracking System of the ALICE experiment and it is the closest detector to the interaction point. As a vertex detector, it has the unique feature of generating a trigger signal that contributes to the L0 trigger of the ALICE experiment. The SPD started collecting data since the very first pp collisions at LHC in 2009 and since then it has taken part in all pp, Pb-Pb and p-Pb data taking campaigns. This contribution will present the main features of the SPD, the detector performance and the operational experience, including calibration and optimization activities from Run 1 to Run 2.

  20. The Role of Collagen Charge Clusters in the Modulation of Matrix Metalloproteinase Activity*

    PubMed Central

    Lauer, Janelle L.; Bhowmick, Manishabrata; Tokmina-Roszyk, Dorota; Lin, Yan; Van Doren, Steven R.; Fields, Gregg B.

    2014-01-01

    Members of the matrix metalloproteinase (MMP) family selectively cleave collagens in vivo. Several substrate structural features that direct MMP collagenolysis have been identified. The present study evaluated the role of charged residue clusters in the regulation of MMP collagenolysis. A series of 10 triple-helical peptide (THP) substrates were constructed in which either Lys-Gly-Asp or Gly-Asp-Lys motifs replaced Gly-Pro-Hyp (where Hyp is 4-hydroxy-l-proline) repeats. The stabilities of THPs containing the two different motifs were analyzed, and kinetic parameters for substrate hydrolysis by six MMPs were determined. A general trend for virtually all enzymes was that, as Gly-Asp-Lys motifs were moved from the extreme N and C termini to the interior next to the cleavage site sequence, kcat/Km values increased. Additionally, all Gly-Asp-Lys THPs were as good or better substrates than the parent THP in which Gly-Asp-Lys was not present. In turn, the Lys-Gly-Asp THPs were also always better substrates than the parent THP, but the magnitude of the difference was considerably less compared with the Gly-Asp-Lys series. Of the MMPs tested, MMP-2 and MMP-9 most greatly favored the presence of charged residues with preference for the Gly-Asp-Lys series. Lys-Gly-(Asp/Glu) motifs are more commonly found near potential MMP cleavage sites than Gly-(Asp/Glu)-Lys motifs. As Lys-Gly-Asp is not as favored by MMPs as Gly-Asp-Lys, the Lys-Gly-Asp motif appears advantageous over the Gly-Asp-Lys motif by preventing unwanted MMP hydrolysis. More specifically, the lack of Gly-Asp-Lys clusters may diminish potential MMP-2 and MMP-9 collagenolytic activity. The present study indicates that MMPs have interactions spanning the P23–P23′ subsites of collagenous substrates. PMID:24297171

  1. The role of collagen charge clusters in the modulation of matrix metalloproteinase activity.

    PubMed

    Lauer, Janelle L; Bhowmick, Manishabrata; Tokmina-Roszyk, Dorota; Lin, Yan; Van Doren, Steven R; Fields, Gregg B

    2014-01-24

    Members of the matrix metalloproteinase (MMP) family selectively cleave collagens in vivo. Several substrate structural features that direct MMP collagenolysis have been identified. The present study evaluated the role of charged residue clusters in the regulation of MMP collagenolysis. A series of 10 triple-helical peptide (THP) substrates were constructed in which either Lys-Gly-Asp or Gly-Asp-Lys motifs replaced Gly-Pro-Hyp (where Hyp is 4-hydroxy-L-proline) repeats. The stabilities of THPs containing the two different motifs were analyzed, and kinetic parameters for substrate hydrolysis by six MMPs were determined. A general trend for virtually all enzymes was that, as Gly-Asp-Lys motifs were moved from the extreme N and C termini to the interior next to the cleavage site sequence, kcat/Km values increased. Additionally, all Gly-Asp-Lys THPs were as good or better substrates than the parent THP in which Gly-Asp-Lys was not present. In turn, the Lys-Gly-Asp THPs were also always better substrates than the parent THP, but the magnitude of the difference was considerably less compared with the Gly-Asp-Lys series. Of the MMPs tested, MMP-2 and MMP-9 most greatly favored the presence of charged residues with preference for the Gly-Asp-Lys series. Lys-Gly-(Asp/Glu) motifs are more commonly found near potential MMP cleavage sites than Gly-(Asp/Glu)-Lys motifs. As Lys-Gly-Asp is not as favored by MMPs as Gly-Asp-Lys, the Lys-Gly-Asp motif appears advantageous over the Gly-Asp-Lys motif by preventing unwanted MMP hydrolysis. More specifically, the lack of Gly-Asp-Lys clusters may diminish potential MMP-2 and MMP-9 collagenolytic activity. The present study indicates that MMPs have interactions spanning the P23-P23' subsites of collagenous substrates.

  2. Extracellular matrix-specific focal adhesions in vascular smooth muscle produce mechanically active adhesion sites

    PubMed Central

    Sun, Zhe; Martinez-Lemus, Luis A.; Hill, Michael A.; Meininger, Gerald A.

    2008-01-01

    Integrin-mediated mechanotransduction in vascular smooth muscle cells (VSMCs) plays an important role in the physiological control of tissue blood flow and vascular resistance. To test whether force applied to specific extracellular matrix (ECM)-integrin interactions could induce myogenic-like mechanical activity at focal adhesion sites, we used atomic force microscopy (AFM) to apply controlled forces to specific ECM adhesion sites on arteriolar VSMCs. The tip of AFM probes were fused with a borosilicate bead (2∼5 μm) coated with fibronectin (FN), collagen type I (CNI), laminin (LN), or vitronectin (VN). ECM-coated beads induced clustering of α5- and β3-integrins and actin filaments at sites of bead-cell contact indicative of focal adhesion formation. Step increases of an upward (z-axis) pulling force (800∼1,600 pN) applied to the bead-cell contact site for FN-specific focal adhesions induced a myogenic-like, force-generating response from the VSMC, resulting in a counteracting downward pull by the cell. This micromechanical event was blocked by cytochalasin D but was enhanced by jasplakinolide. Function-blocking antibodies to α5β1- and αvβ3-integrins also blocked the micromechanical cell event in a concentration-dependent manner. Similar pulling experiments with CNI, VN, or LN failed to induce myogenic-like micromechanical events. Collectively, these results demonstrate that mechanical force applied to integrin-FN adhesion sites induces an actin-dependent, myogenic-like, micromechanical event. Focal adhesions formed by different ECM proteins exhibit different mechanical characteristics, and FN appears of particular relevance in its ability to strongly attach to VSMCs and to induce myogenic-like, force-generating reactions from sites of focal adhesion in response to externally applied forces. PMID:18495809

  3. High responsivity CMOS imager pixel implemented in SOI technology

    NASA Technical Reports Server (NTRS)

    Zheng, X.; Wrigley, C.; Yang, G.; Pain, B.

    2000-01-01

    Availability of mature sub-micron CMOS technology and the advent of the new low noise active pixel sensor (APS) concept have enabled the development of low power, miniature, single-chip, CMOS digital imagers in the decade of the 1990's.

  4. Pixel Analysis and Plasma Dynamics Characterized by Photospheric Spectral Data

    NASA Astrophysics Data System (ADS)

    Rasca, Anthony P.; Chen, James; Pevtsov, Alexei A.

    2016-05-01

    Recent observations of the photosphere using high spatial and temporal resolutions show small dynamic features at the resolving limit during emerging flux events. However, line-of-sight (LOS) magnetogram pixels only contain the net uncanceled magnetic flux, which is expected to increase for fixed regions as resolution limits improve. A new pixel dynamics method uses spectrographic images to characterize photospheric absorption line profiles by variations in line displacement, width, asymmetry, and peakedness and is applied to quiet-sun regions, active regions with no eruption, and an active region with an ongoing eruption. Using Stokes I images from SOLIS/VSM on 2012 March 13, variations in line width and peakedness of Fe I 6301.5 Å are shown to have a strong spatial and temporal relationship with an M7.9 X-ray flare originating from NOAA 11429. This relationship is observed as a flattening in the line profile as the X-ray flare approaches peak intensity and was not present in area scans of a non-eruptive active region on 2011 April 14. These results are used to estimate dynamic plasma properties on sub-pixel scales and provide both spatial and temporal information of sub-pixel activity at the photosphere. The analysis can be extended to include the full Stokes parameters and study signatures of magnetic fields and coupled plasma properties.

  5. Commissioning of the CMS Forward Pixel Detector

    SciTech Connect

    Kumar, Ashish; /SUNY, Buffalo

    2008-12-01

    The Compact Muon Solenoid (CMS) experiment is scheduled for physics data taking in summer 2009 after the commissioning of high energy proton-proton collisions at Large Hadron Collider (LHC). At the core of the CMS all-silicon tracker is the silicon pixel detector, comprising three barrel layers and two pixel disks in the forward and backward regions, accounting for a total of 66 million channels. The pixel detector will provide high-resolution, 3D tracking points, essential for pattern recognition and precise vertexing, while being embedded in a hostile radiation environment. The end disks of the pixel detector, known as the Forward Pixel detector, has been assembled and tested at Fermilab, USA. It has 18 million pixel cells with dimension 100 x 150 {micro}m{sup 2}. The complete forward pixel detector was shipped to CERN in December 2007, where it underwent extensive system tests for commissioning prior to the installation. The pixel system was put in its final place inside the CMS following the installation and bake out of the LHC beam pipe in July 2008. It has been integrated with other sub-detectors in the readout since September 2008 and participated in the cosmic data taking. This report covers the strategy and results from commissioning of CMS forward pixel detector at CERN.

  6. A 65 nm pixel readout ASIC with quick transverse momentum discrimination capabilities for the CMS Tracker at HL-LHC

    NASA Astrophysics Data System (ADS)

    Ceresa, D.; Kaplon, J.; Francisco, R.; Caratelli, A.; Kloukinas, K.; Marchioro, A.

    2016-01-01

    A readout ASIC for the hybrid pixel detector with the capability of performing quick recognition of particles with high transverse momentum has been designed for the requirements of the CMS Outer Tracker at the High Luminosity LHC . The particle momentum dicrimination capability represents the main challenge for this design together with the low power requirement: the constraint of low mass for the new tracker dictates a total power budget of less than 100 mW/cm2. The choice of a 65 nm CMOS technology has made it possible to satisfy this power requirement despite the fairly large amount of logic necessary to perform the momentum discrimination and the continuous operation at 40 MHz. Several techniques for low power have been used to implement this logic that performs cluster reduction, position offset correction and coordinate encoding. A prototype chip including a large part of the final functionality and the full front-end has been realized and comprises a matrix of 16 by 3 rectangular pixels of 100 μm × 1446 μm, providing 7.65 mm2 of segmented active area. Measurements of the analog front-end characteristics closely match the simulations and confirm the consumption of < 30 μA per pixel. Front-end characterization and irradiation results up to 150 MRad are also reported.

  7. 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.

  8. 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

  9. Implementation of TDI based digital pixel ROIC with 15μm pixel pitch

    NASA Astrophysics Data System (ADS)

    Ceylan, Omer; Shafique, Atia; Burak, A.; Caliskan, Can; Abbasi, Shahbaz; Yazici, Melik; Gurbuz, Yasar

    2016-05-01

    A 15um pixel pitch digital pixel for LWIR time delay integration (TDI) applications is implemented which occupies one fourth of pixel area compared to previous digital TDI implementation. TDI is implemented on 8 pixels with oversampling rate of 2. ROIC provides 16 bits output with 8 bits of MSB and 8 bits of LSB. Pixel can store 75 M electrons with a quantization noise of 500 electrons. Digital pixel TDI implementation is advantageous over analog counterparts considering power consumption, chip area and signal-to-noise ratio. Digital pixel TDI ROIC is fabricated with 0.18um CMOS process. In digital pixel TDI implementation photocurrent is integrated on a capacitor in pixel and converted to digital data in pixel. This digital data triggers the summation counters which implements TDI addition. After all pixels in a row contribute, the summed data is divided to the number of TDI pixels(N) to have the actual output which is square root of N improved version of a single pixel output in terms of signal-to-noise-ratio (SNR).

  10. 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.

  11. Single chip camera active pixel sensor

    NASA Technical Reports Server (NTRS)

    Shaw, Timothy (Inventor); Pain, Bedabrata (Inventor); Olson, Brita (Inventor); Nixon, Robert H. (Inventor); Fossum, Eric R. (Inventor); Panicacci, Roger A. (Inventor); Mansoorian, Barmak (Inventor)

    2003-01-01

    A totally digital single chip camera includes communications to operate most of its structure in serial communication mode. The digital single chip camera include a D/A converter for converting an input digital word into an analog reference signal. The chip includes all of the necessary circuitry for operating the chip using a single pin.

  12. Trimer Enhancement Mutation Effects on HIV-1 Matrix Protein Binding Activities

    PubMed Central

    Alfadhli, Ayna; Mack, Andrew; Ritchie, Christopher; Cylinder, Isabel; Harper, Logan; Tedbury, Philip R.; Freed, Eric O.

    2016-01-01

    ABSTRACT The HIV-1 matrix (MA) protein is the amino-terminal domain of the HIV-1 precursor Gag (Pr55Gag) protein. MA binds to membranes and RNAs, helps transport Pr55Gag proteins to virus assembly sites at the plasma membranes of infected cells, and facilitates the incorporation of HIV-1 envelope (Env) proteins into virions by virtue of an interaction with the Env protein cytoplasmic tails (CTs). MA has been shown to crystallize as a trimer and to organize on membranes in hexamer lattices. MA mutations that localize to residues near the ends of trimer spokes have been observed to impair Env protein assembly into virus particles, and several of these are suppressed by the 62QR mutation at the hubs of trimer interfaces. We have examined the binding activities of wild-type (WT) MA and 62QR MA variants and found that the 62QR mutation stabilized MA trimers but did not alter the way MA proteins organized on membranes. Relative to WT MA, the 62QR protein showed small effects on membrane and RNA binding. However, 62QR proteins bound significantly better to Env CTs than their WT counterparts, and CT binding efficiencies correlated with trimerization efficiencies. Our data suggest a model in which multivalent binding of trimeric HIV-1 Env proteins to MA trimers contributes to the process of Env virion incorporation. IMPORTANCE The HIV-1 Env proteins assemble as trimers, and incorporation of the proteins into virus particles requires an interaction of Env CT domains with the MA domains of the viral precursor Gag proteins. Despite this knowledge, little is known about the mechanisms by which MA facilitates the virion incorporation of Env proteins. To help elucidate this process, we examined the binding activities of an MA mutant that stabilizes MA trimers. We found that the mutant proteins organized similarly to WT proteins on membranes, and that mutant and WT proteins revealed only slight differences in their binding to RNAs or lipids. However, the mutant proteins showed

  13. A metamaterial-based single pixel imaging system (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Padilla, Willie J.

    2016-09-01

    Electromagnetic metamaterials have demonstrated unprecedented control over light matter interactions and have realized exotic responses difficult to achieve with natural materials. The ability to achieve real-time control of novel responses exhibited by electromagnetic metamaterials has led to the realization of metadevices and metasystems. Here we experimentally demonstrate two realizations of single pixel imaging systems that rely entirely on all-electronic metamaterial spatial light modulators. The metasystem enables images to be digitally encoded with various measurement matrix coefficients, thus permitting high speed and fidelity imaging.

  14. Achievements of the ATLAS upgrade planar pixel sensors R&D project

    NASA Astrophysics Data System (ADS)

    Calderini, G.

    2014-11-01

    This paper reports on recent accomplishments and ongoing work of the ATLAS Planar Pixel Sensors R&D project. Special attention is given in particular to new testbeam results obtained with highly irradiated sensors, developments in the field of slim and active edges and first step towards prototypes of future pixel modules.

  15. Gelatinolytic activity of matrix metalloproteinase-2 and matrix metalloproteinase-9 in rat brain after implantation of 9L rat glioma cells.

    PubMed

    Zhao, J X; Yang, L P; Wang, Y F; Qin, L P; Liu, D Q; Bai, C X; Nan, X; Shi, S S; Pei, X J

    2007-05-01

    The matrix metalloproteinases (MMPs) have come to be highlighted by their close relation to the cell invasion of gliomas. The inhibitors of MMPs have undergone extensive development because of its effectiveness against tumor invasion and angiogenesis. Therefore, a suitable animal model is necessary for searching new MMPs inhibitors against gliomas. In this study, we established an experimental model by implanting 9L glioma cells stereotactically into Fisher344 (F344) rat's brain, and the expression and enzymatic activity of MMP-2 and MMP-9 in 9L glioma cells and in tumor tissue was determined by means of reverse transcription polymerase chain reaction (RT-PCR), sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) zymography, in situ film zymography and immunostaining. The results of RT-PCR showed that the mRNA level of MMP-2 in 9L glioma cells was higher than that of MMP-9, and the mRNA expression of MMP-9 was increased along with the growth of malignant gliomas. SDS-PAGE zymography revealed that the expression of MMP-2 and MMP-9 were significantly increased in tumor tissues, and the MMP-9 wasn't detected in normal tissue. The positive stain of MMP-2 and MMP-9 was enhanced with the growth of malignant gliomas, especially for MMP-9. The expression of active gelatinase was found in tumor tissue. In conclusion, the expression of active MMP-2 and MMP-9 was increased in 9L/F344 rat brain during the growth of malignant gliomas at different time intervals, which indicate that 9L/F344 animal model may be a prospective animal model to test new MMPs inhibitors.

  16. Molybdenum metallization, and step-induced defects in active-matrix liquid crystal displays

    NASA Astrophysics Data System (ADS)

    Quli, Farhat Abbas

    The objective of this work was to identify the causes of the step-induced preferential etching which occurs during the patterning of molybdenum (Mo) interconnects for the source/drain line metallization of the thin-film transistor array of active matrix liquid crystal displays. The morphology of Mo films deposited on steps under various conditions using sputtering and electron beam physical vapor deposition (EB-PVD) was studied to identify the causes of preferential etching, and determine processing conditions leading to defect-free interconnects. It was found that columnar growth domains grown from the steps were misaligned with the columnar growth from the substrate, causing the creation of high-angle grain boundaries where the columns impinged upon one another. This boundary region is believed to be responsible for the preferential etching in the Mo films. Columnar growth of silicon dioxide, an amorphous film, did not result in preferential etching due to the lack of grain boundaries. Neon (Ne) sputtering of Mo did not lead to amorphous films due to higher film bombardment during Ne sputtering, as reported by other researchers. Instead, the low rate of deposition during Ne sputtering was found to cause the incorporation of high amounts of impurities that lead to amorphization of the growing film. At extremely low rates and high impurity concentrations, it was found that the film grew in a fcc rather than bcc structure. Mo deposited under high levels of argon ion bombardment was found to have an isotropic rather than columnar morphology which led to interconnects that were free from preferential etching. The maximum ratio of depositing atoms to bombarding ions necessary to modify the microstructure was found to be 1.5 for Mo deposited by EB-PVD at 400°C substrate temperature and --600 volts substrate bias. The processing window for bias sputtering conditions leading to an isotropic morphology was also identified. Thermally induced grain growth in metal films was

  17. Spectroscopic and imaging capabilities of a pixellated photon counting system

    NASA Astrophysics Data System (ADS)

    Amendolia, S. R.; Bisogni, M. G.; Bottigli, U.; Delogu, P.; Dipasquale, G.; Fantacci, M. E.; Marchi, A.; Marzulli, V. M.; Oliva, P.; Palmiero, R.; Rosso, V.; Stefanini, A.; Stumbo, S.; Zucca, S.

    2001-06-01

    We are studying the performance of various thickness GaAs pixel detectors bump-bonded to a dedicated photon counting chip (PCC) for medical imaging applications in different energy ranges. In this work we present the experimental results obtained with a 600 μm thick pixel matrix (64×64 square pixels, 170 μm side) in the 60-140 keV energy range to evaluate the possible use of such a system in the nuclear medicine field. In particular, we have measured the spectroscopic properties of the detector (charge collection efficiency, energy resolution and detection efficiency) and evaluated the discrimination capability of the electronics. Then we have measured the imaging properties of the whole system in terms of Point Spread Function and using a home made thyroid phantom. We present also a comparison with a traditional gamma camera and an evaluation, made by both experimental measurements and software simulations, of the imaging characteristics related to the use of a collimation system.

  18. High stroke pixel for a deformable mirror

    DOEpatents

    Miles, Robin R.; Papavasiliou, Alexandros P.

    2005-09-20

    A mirror pixel that can be fabricated using standard MEMS methods for a deformable mirror. The pixel is electrostatically actuated and is capable of the high deflections needed for spaced-based mirror applications. In one embodiment, the mirror comprises three layers, a top or mirror layer, a middle layer which consists of flexures, and a comb drive layer, with the flexures of the middle layer attached to the mirror layer and to the comb drive layer. The comb drives are attached to a frame via spring flexures. A number of these mirror pixels can be used to construct a large mirror assembly. The actuator for the mirror pixel may be configured as a crenellated beam with one end fixedly secured, or configured as a scissor jack. The mirror pixels may be used in various applications requiring high stroke adaptive optics.

  19. Digital radiology using active matrix readout of amorphous selenium: radiation hardness of cadmium selenide thin film transistors.

    PubMed

    Zhao, W; Waechter, D; Rowlands, J A

    1998-04-01

    A flat-panel x-ray imaging detector using active matrix readout of amorphous selenium (a-Se) is being investigated for digital radiography and fluoroscopy. The active matrix consists of a two-dimensional array of thin film transistors (TFTs). Radiation penetrating through the a-Se layer will interact with the TFTs and it is important to ensure that radiation induced changes will not affect the operation of the x-ray imaging detector. The methodology of the present work is to investigate the effects of radiation on the characteristic curves of the TFTs using individual TFT samples made with cadmium selenide (CdSe) semiconductor. Four characteristic parameters, i.e., threshold voltage, subthreshold swing, field effect mobility, and leakage current, were examined. This choice of parameters was based on the well established radiation damage mechanisms for crystalline silicon metal-oxide-semiconductor field-effect transistors (MOSFETs), which have a similar principle of operation as CdSe TFTs. It was found that radiation had no measurable effect on the leakage current and the field effect mobility. However, radiation shifted the threshold voltage and increased the subthreshold swing. But even the estimated lifetime dose (50 Gy) of a diagnostic radiation detector will not affect the normal operation of an active matrix x-ray detector made with CdSe TFTs. The mechanisms of the effects of radiation will be discussed and compared with those for MOSFETs and hydrogenated amorphous silicon (a-Si:H) TFTs.

  20. 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

  1. Smart-Pixel Array Processors Based on Optimal Cellular Neural Networks for Space Sensor Applications

    NASA Technical Reports Server (NTRS)

    Fang, Wai-Chi; Sheu, Bing J.; Venus, Holger; Sandau, Rainer

    1997-01-01

    A smart-pixel cellular neural network (CNN) with hardware annealing capability, digitally programmable synaptic weights, and multisensor parallel interface has been under development for advanced space sensor applications. The smart-pixel CNN architecture is a programmable multi-dimensional array of optoelectronic neurons which are locally connected with their local neurons and associated active-pixel sensors. Integration of the neuroprocessor in each processor node of a scalable multiprocessor system offers orders-of-magnitude computing performance enhancements for on-board real-time intelligent multisensor processing and control tasks of advanced small satellites. The smart-pixel CNN operation theory, architecture, design and implementation, and system applications are investigated in detail. The VLSI (Very Large Scale Integration) implementation feasibility was illustrated by a prototype smart-pixel 5x5 neuroprocessor array chip of active dimensions 1380 micron x 746 micron in a 2-micron CMOS technology.

  2. Development of a pixel ionization chamber for beam monitor in proton therapy

    NASA Astrophysics Data System (ADS)

    La Rosa, A.; Garella, M. A.; Attili, A.; Bourhaleb, F.; Cirio, R.; Donetti, M.; Giordanengo, S.; Givehchi, N.; Marchetto, F.; Mazza, G.; Meyroneinc, S.; Pecka, A.; Peroni, C.; Pittà, G.

    2007-03-01

    We have developed a detector to be used as monitor for proton therapy beam lines. The detector is a 2-D parallel plate ionization chamber, with the anode segmented in 1024 square pixels arranged in a 32×32 matrix. The detector characterization is presented.

  3. Relationship between activation volume and polymer matrix effects on photochromic performance: bridging molecular parameter to macroscale effect.

    PubMed

    Shima, Kentaro; Mutoh, Katsuya; Kobayashi, Yoichi; Abe, Jiro

    2015-02-19

    Photochromic compounds have attracted attention as ophthalmic lenses because of their reversible color modulation upon irradiation with light. However, the efficiency of the photochromism is strongly affected by their surrounding because of the structural changes concomitant with the photochromism, which causes the decrease in the photochromic performance in the polymer matrix. Therefore, the clarification of the degree of the structural changes is necessary to apply to the ophthalmic lenses. Bridged imidazole dimers are one of the fast photoswitch molecules possessing high photochromic quantum yield and durability. Although the enhancement of the photochromic properties of bridged imidazole dimers has been vigorously studied, the quantitative information about the structural changes has not been revealed in detail. In this study, we investigated the pressure effects on the photochromic properties of bridged imidazole dimers. The activation volume for the thermal back-reaction of the photogenerated biradical species becomes an effective measure to predict the degree of the structural change during the photochromic reaction. We revealed that the smaller activation volume is suitable for keeping the efficient photochromic reaction in the polymer matrix because the photochromic reaction is not affected by the surroundings. These fundamental insights into the molecular dynamics provide valuable information to develop fast photochromic compounds that are suitable for the use in the polymer matrix and pressure sensitive photochromic materials.

  4. It's not the pixel count, you fool

    NASA Astrophysics Data System (ADS)

    Kriss, Michael A.

    2012-01-01

    The first thing a "marketing guy" asks the digital camera engineer is "how many pixels does it have, for we need as many mega pixels as possible since the other guys are killing us with their "umpteen" mega pixel pocket sized digital cameras. And so it goes until the pixels get smaller and smaller in order to inflate the pixel count in the never-ending pixel-wars. These small pixels just are not very good. The truth of the matter is that the most important feature of digital cameras in the last five years is the automatic motion control to stabilize the image on the sensor along with some very sophisticated image processing. All the rest has been hype and some "cool" design. What is the future for digital imaging and what will drive growth of camera sales (not counting the cell phone cameras which totally dominate the market in terms of camera sales) and more importantly after sales profits? Well sit in on the Dark Side of Color and find out what is being done to increase the after sales profits and don't be surprised if has been done long ago in some basement lab of a photographic company and of course, before its time.

  5. Ciglitazone ameliorates homocysteine-mediated mitochondrial translocation and matrix metalloproteinase-9 activation in endothelial cells by inducing peroxisome proliferator activated receptor-gamma activity.

    PubMed

    Tyagi, N; Moshal, K S; Sen, U; Lominadze, D; Ovechkin, A V; Tyagi, S C

    2006-12-31

    The activation of peroxisome proliferator activated receptor-gamma (PPARgamma) ameliorates the homocysteine (Hcy)-induced matrix metalloproteinase (MMP) by decreasing reactive oxygen species (ROS) production. However, the mechanism by which Hcy induces ROS generation and MMP activation is unclear. We hypothesize that Hcy increases NADH oxidase (Nox-4) and decreases thioredoxin (Trx). This leads to translocation of Nox-4 into the mitochondria and decrease in Trx. In addition, activation of PPARgamma ameliorates the translocation of Nox-4 into mitochondria and MMP-9 activation. Mouse aortic vascular endothelial cells (MVEC) were cultured in the presence or absence of 100 microM Hcy. The cells were pre-treated with ciglitazone (CZ, 150 microM). Activity of PPARgamma activity was measured by electrophoretic mobility shift assay (EMSA) and antibody super shift assay. In situ generation of ROS was measured using 2,7-dichlorofluorescin (DCF) as a probe. The expression of Nox-4 and Trx were measured by quantitative real-time polymerase chain reaction (Q-RT-PCR). The translocation of Nox-4 was measured by 2-D gel analysis. To determine the levels of Nox-4 and Trx, the mitochondria and cytosol were separated and Western blot analysis was preformed. The MMP-9 activity was measured by gelatin-zymography. The results suggested that CZ activated endothelial PPARgamma in the presence of Hcy. Production of ROS was ameliorated by PPARgamma activation. Expression of Nox-4 was increased, while production of Trx was decreased by Hcy. However, the treatment with CZ normalized the levels of Nox-4 and Trx. Nox-4 was translocated into mitochondria in Hcy-treated endothelial cells. This translocation was associated with decreased production of Trx in mitochondria. The treatment with CZ blocked this translocation and increased Trx levels in mitochondria. Hcy-mediated MMP-9 activity was decreased in cells pre-treated with CZ. These results suggest that Hcy increases NADH oxidase and

  6. Active matrix organic light-emitting diode (AMOLED) performance and life test results

    NASA Astrophysics Data System (ADS)

    Fellowes, David A.; Wood, Michael V.; Hastings, Arthur R., Jr.; Draper, Russell S.; Ghosh, Amalkumar; Prache, Olivier; Wacyk, Ihor; Ali, Tariq; Khayrullin, Ilyas

    2011-06-01

    The US Army and eMagin Corporation established a Cooperative Research and Development Agreement (CRADA) to characterize the ongoing improvements in the lifetime of OLED displays. This CRADA also called for the evaluation of OLED performance as the need arises, especially when new products are developed or when a previously untested parameter needs to be understood. In 2006, eMagin Corporation developed long-life OLED-XL devices for use in their AMOLED microdisplays for head-worn applications. Through research and development programs from 2007 to 2010 with the US Government, eMagin made additional improvements in OLED life and developed the first SXGA (1280 X 1024 triad pixels) OLED microdisplay. US Army RDECOM CERDEC NVESD conducted life and performance tests on these displays, publishing results at the 2007, 2008, 2009, and 2010 SPIE Defense and Security Symposia1,2,3,4. Life and performance tests have continued through 2010, and this data will be presented 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 desirable.

  7. Wild-type amyloid beta 1-40 peptide induces vascular smooth muscle cell death independently from matrix metalloprotease activity.

    PubMed

    Blaise, Régis; Mateo, Véronique; Rouxel, Clotilde; Zaccarini, François; Glorian, Martine; Béréziat, Gilbert; Golubkov, Vladislav S; Limon, Isabelle

    2012-06-01

    Cerebral amyloid angiopathy (CAA) is an important cause of intracerebral hemorrhages in the elderly, characterized by amyloid-β (Aβ) peptide accumulating in central nervous system blood vessels. Within the vessel walls, Aβ-peptide deposits [composed mainly of wild-type (WT) Aβ(1-40) peptide in sporadic forms] induce impaired adhesion of vascular smooth muscle cells (VSMCs) to the extracellular matrix (ECM) associated with their degeneration. This process often results in a loss of blood vessel wall integrity and ultimately translates into cerebral ischemia and microhemorrhages, both clinical features of CAA. In this study, we decipher the molecular mechanism of matrix metalloprotease (MMP)-2 activation in WT-Aβ(1-40) -treated VSMC and provide evidence that MMP activity, although playing a critical role in cell detachment disrupting ECM components, is not involved in the WT-Aβ(1-40) -induced degeneration of VSMCs. Indeed, whereas this peptide clearly induced VSMC apoptosis, neither preventing MMP-2 activity nor hampering the expression of membrane type1-MMP, or preventing tissue inhibitors of MMPs-2 (TIMP-2) recruitment (two proteins evidenced here as involved in MMP-2 activation), reduced the number of dead cells. Even the use of broad-range MMP inhibitors (GM6001 and Batimastat) did not affect WT-Aβ(1-40) -induced cell apoptosis. Our results, in contrast to those obtained using the Aβ(1-40) Dutch variant suggesting a link between MMP-2 activity, VSMC mortality and degradation of specific matrix components, indicate that the ontogenesis of the Dutch familial and sporadic forms of CAAs is different. ECM degradation and VSMC degeneration would be tightly connected in the Dutch familial form while being two independent processes in sporadic forms of CAA.

  8. Platelet hyaluronidase-2: an enzyme that translocates to the surface upon activation to function in extracellular matrix degradation

    PubMed Central

    Albeiroti, Sami; Ayasoufi, Katayoun; Hill, David R.; Shen, Bo

    2015-01-01

    Following injury, platelets rapidly interact with the exposed extracellular matrix (ECM) of the vessel wall and the surrounding tissues. Hyaluronan (HA) is a major glycosaminoglycan component of the ECM and plays a significant role in regulating inflammation. We have recently reported that human platelets degrade HA from the surfaces of activated endothelial cells into fragments capable of inducing immune responses by monocytes. We also showed that human platelets contain the enzyme hyaluronidase-2 (HYAL2), one of two major hyaluronidases that digest HA in somatic tissues. The deposition of HA increases in inflamed tissues in several inflammatory diseases, including inflammatory bowel disease (IBD). We therefore wanted to define the mechanism by which platelets degrade HA in the inflamed tissues. In this study, we show that human platelets degrade the proinflammatory matrix HA through the activity of HYAL2 and that platelet activation causes the immediate translocation of HYAL2 from a distinct population of α-granules to platelet surfaces where it exerts its catalytic activity. Finally, we show that patients with IBD have lower platelet HYAL2 levels and activity than healthy controls. PMID:25411425

  9. 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

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

    PubMed

    Grass, G Daniel; Toole, Bryan P

    2015-11-24

    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.

  11. Platelet hyaluronidase-2: an enzyme that translocates to the surface upon activation to function in extracellular matrix degradation.

    PubMed

    Albeiroti, Sami; Ayasoufi, Katayoun; Hill, David R; Shen, Bo; de la Motte, Carol A

    2015-02-26

    Following injury, platelets rapidly interact with the exposed extracellular matrix (ECM) of the vessel wall and the surrounding tissues. Hyaluronan (HA) is a major glycosaminoglycan component of the ECM and plays a significant role in regulating inflammation. We have recently reported that human platelets degrade HA from the surfaces of activated endothelial cells into fragments capable of inducing immune responses by monocytes. We also showed that human platelets contain the enzyme hyaluronidase-2 (HYAL2), one of two major hyaluronidases that digest HA in somatic tissues. The deposition of HA increases in inflamed tissues in several inflammatory diseases, including inflammatory bowel disease (IBD). We therefore wanted to define the mechanism by which platelets degrade HA in the inflamed tissues. In this study, we show that human platelets degrade the proinflammatory matrix HA through the activity of HYAL2 and that platelet activation causes the immediate translocation of HYAL2 from a distinct population of α-granules to platelet surfaces where it exerts its catalytic activity. Finally, we show that patients with IBD have lower platelet HYAL2 levels and activity than healthy controls.

  12. 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

    2016-01-05

    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.

  13. LISe pixel detector for neutron imaging

    NASA Astrophysics Data System (ADS)

    Herrera, Elan; Hamm, Daniel; Wiggins, Brenden; Milburn, Rob; Burger, Arnold; Bilheux, Hassina; Santodonato, Louis; Chvala, Ondrej; Stowe, Ashley; Lukosi, Eric

    2016-10-01

    Semiconducting lithium indium diselenide, 6LiInSe2 or LISe, has promising characteristics for neutron detection applications. The 95% isotopic enrichment of 6Li results in a highly efficient thermal neutron-sensitive material. In this study, we report on a proof-of-principle investigation of a semiconducting LISe pixel detector to demonstrate its potential as an efficient neutron imager. The LISe pixel detector had a 4×4 of pixels with a 550 μm pitch on a 5×5×0.56 mm3 LISe substrate. An experimentally verified spatial resolution of 300 μm was observed utilizing a super-sampling technique.

  14. Per-Pixel Lighting Data Analysis

    SciTech Connect

    Inanici, Mehlika

    2005-08-01

    This report presents a framework for per-pixel analysis of the qualitative and quantitative aspects of luminous environments. Recognizing the need for better lighting analysis capabilities and appreciating the new measurement abilities developed within the LBNL Lighting Measurement and Simulation Toolbox, ''Per-pixel Lighting Data Analysis'' project demonstrates several techniques for analyzing luminance distribution patterns, luminance ratios, adaptation luminance and glare assessment. The techniques are the syntheses of the current practices in lighting design and the unique practices that can be done with per-pixel data availability. Demonstrated analysis techniques are applicable to both computer-generated and digitally captured images (physically-based renderings and High Dynamic Range photographs).

  15. Anode readout for pixellated CZT detectors

    NASA Astrophysics Data System (ADS)

    Narita, Tomohiko; Grindlay, Jonathan E.; Hong, Jaesub; Niestemski, Francis C.

    2004-02-01

    Determination of the photon interaction depth offers numerous advantages for an astronomical hard X-ray telescope. The interaction depth is typically derived from two signals: anode and cathode, or collecting and non-collecting electrodes. We present some preliminary results from our depth sensing detectors using only the anode pixel signals. By examining several anode pixel signals simultaneously, we find that we can estimate the interaction depth, and get sub-pixel 2-D position resolution. We discuss our findings and the requirements for future ASIC development.

  16. Photovoltaic Pixels for Neural Stimulation: Circuit Models and Performance.

    PubMed

    Boinagrov, David; Lei, Xin; Goetz, Georges; Kamins, Theodore I; Mathieson, Keith; Galambos, Ludwig; Harris, James S; Palanker, Daniel

    2016-02-01

    Photovoltaic conversion of pulsed light into pulsed electric current enables optically-activated neural stimulation with miniature wireless implants. In photovoltaic retinal prostheses, patterns of near-infrared light projected from video goggles onto subretinal arrays of photovoltaic pixels are converted into patterns of current to stimulate the inner retinal neurons. We describe a model of these devices and evaluate the performance of photovoltaic circuits, including the electrode-electrolyte interface. Characteristics of the electrodes measured in saline with various voltages, pulse durations, and polarities were modeled as voltage-dependent capacitances and Faradaic resistances. The resulting mathematical model of the circuit yielded dynamics of the electric current generated by the photovoltaic pixels illuminated by pulsed light. Voltages measured in saline with a pipette electrode above the pixel closely matched results of the model. Using the circuit model, our pixel design was optimized for maximum charge injection under various lighting conditions and for different stimulation thresholds. To speed discharge of the electrodes between the pulses of light, a shunt resistor was introduced and optimized for high frequency stimulation.

  17. 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

  18. 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.

  19. Variance of matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) concentrations in activated, concentrated platelets from healthy male donors

    PubMed Central

    2014-01-01

    Background The use of autologous blood concentrates, such as activated, concentrated platelets, in orthopaedic clinical applications has had mixed results. Research on this topic has focused on growth factors and cytokines, with little directed towards matrix metalloproteinases (MMPs) which are involved in post-wound tissue remodeling. Methods In this study, the authors measured the levels of MMP-2, MMP-9 and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), in activated platelets derived from blood of healthy, male volunteers (n = 92), 19 to 60 years old. The levels of the natural inhibitors of these proteases, tissue inhibitor of metalloproteinase 1 (TIMP-1), TIMP-2 and TIMP-4 were also assessed. Results Notably, there was no significant change in concentration with age in four of six targets tested. However, TIMP-2 and TIMP-4 demonstrated a statistically significant increase in concentration for subjects older than 30 years of age compared to those 30 years and younger (P = 0.04 and P = 0.04, respectively). Conclusion TIMP-2 and TIMP-4 are global inhibitors of MMPs, including MMP-2 (Gelatinase A). MMP-2 targets native collagens, gelatin and elastin to remodel the extracellular matrix during wound healing. A decreased availability of pharmacologically active MMP-2 may diminish the effectiveness of the use of activated, concentrated platelets from older patients, and may also contribute to longer healing times in this population. PMID:24766991

  20. Pixels, Imagers and Related Fabrication Methods

    NASA Technical Reports Server (NTRS)

    Pain, Bedabrata (Inventor); Cunningham, Thomas J. (Inventor)

    2014-01-01

    Pixels, imagers and related fabrication methods are described. The described methods result in cross-talk reduction in imagers and related devices by generating depletion regions. The devices can also be used with electronic circuits for imaging applications.

  1. Pixels, Imagers and Related Fabrication Methods

    NASA Technical Reports Server (NTRS)

    Pain, Bedabrata (Inventor); Cunningham, Thomas J. (Inventor)

    2016-01-01

    Pixels, imagers and related fabrication methods are described. The described methods result in cross-talk reduction in imagers and related devices by generating depletion regions. The devices can also be used with electronic circuits for imaging applications.

  2. 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

  3. Toward Multispectral Imaging with Colloidal Metasurface Pixels.

    PubMed

    Stewart, Jon W; Akselrod, Gleb M; Smith, David R; Mikkelsen, Maiken H

    2017-02-01

    Multispectral colloidal metasurfaces are fabricated that exhibit greater than 85% absorption and ≈100 nm linewidths by patterning film-coupled nanocubes in pixels using a fusion of bottom-up and top-down fabrication techniques over wafer-scale areas. With this technique, the authors realize a multispectral pixel array consisting of six resonances between 580 and 1125 nm and reconstruct an RGB image with 9261 color combinations.

  4. Design of the small pixel pitch ROIC

    NASA Astrophysics Data System (ADS)

    Liang, Qinghua; Jiang, Dazhao; Chen, Honglei; Zhai, Yongcheng; Gao, Lei; Ding, Ruijun

    2014-11-01

    Since the technology trend of the third generation IRFPA towards resolution enhancing has steadily progressed,the pixel pitch of IRFPA has been greatly reduced.A 640×512 readout integrated circuit(ROIC) of IRFPA with 15μm pixel pitch is presented in this paper.The 15μm pixel pitch ROIC design will face many challenges.As we all known,the integrating capacitor is a key performance parameter when considering pixel area,charge capacity and dynamic range,so we adopt the effective method of 2 by 2 pixels sharing an integrating capacitor to solve this problem.The input unit cell architecture will contain two paralleled sample and hold parts,which not only allow the FPA to be operated in full frame snapshot mode but also save relatively unit circuit area.Different applications need more matching input unit circuits. Because the dimension of 2×2 pixels is 30μm×30μm, an input stage based on direct injection (DI) which has medium injection ratio and small layout area is proved to be suitable for middle wave (MW) while BDI with three-transistor cascode amplifier for long wave(LW). By adopting the 0.35μm 2P4M mixed signal process, the circuit architecture can make the effective charge capacity of 7.8Me- per pixel with 2.2V output range for MW and 7.3 Me- per pixel with 2.6V output range for LW. According to the simulation results, this circuit works well under 5V power supply and achieves less than 0.1% nonlinearity.

  5. Readout and DAQ for Pixel Detectors

    NASA Astrophysics Data System (ADS)

    Platkevic, Michal

    2010-01-01

    Data readout and acquisition control of pixel detectors demand the transfer of significantly a large amounts of bits between the detector and the computer. For this purpose dedicated interfaces are used which are designed with focus on features like speed, small dimensions or flexibility of use such as digital signal processors, field-programmable gate arrays (FPGA) and USB communication ports. This work summarizes the readout and DAQ system built for state-of-the-art pixel detectors of the Medipix family.

  6. Sunlight activated lanthanide complex for luminescent solar collector applications: effect of waveguide matrix

    NASA Astrophysics Data System (ADS)

    Shahi, Praveen Kumar; Singh, Priyam; Bahadur Rai, Shyam

    2017-02-01

    The performance of Eu(DBM)3Phen complex (EDP) dispersed in PMMA poly-(methyl methacrylate) polymer matrix, as simple planner luminescent solar collectors (LSCs) is demonstrated using spectroscopic and photovoltaic (PV) measurements. The organic ligands absorb ultra-violet-blue (UV-blue) radiation (220–450 nm) very efficiently and transfer its energy to the Eu3+ ion, which gives an intense red emission even in sunlight exposure. The excellent optical properties of EDP in PMMA permit its coating on the front surface of c-Si solar cell (10  ×  10 cm2) for PV measurements. The PV characterizations reveal the improvement in the short circuit current density (J sc) of PV cell and maximum improvement is found to be 4.6% for 2.5 wt% EDP concentration in PMMA matrix. The efficiency of solar cell increases from 17.22% to 18.33% for bare and 2.5% EDP in PMMA. At a higher concentration of EDP, the thin film starts losing its transparency and hence PV efficiency decreases. These results illustrate that a EDP complex combined with a PV cell could work as a prototype of a new generation solar cell.

  7. A relevant enzyme in granulomatous reaction, active matrix metalloproteinase-9, found in bovine Echinococcus granulosus hydatid cyst wall and fluid.

    PubMed

    Marco, M; Baz, A; Fernandez, C; Gonzalez, G; Hellman, U; Salinas, G; Nieto, A

    2006-12-01

    In addition to the ability of matrix metalloproteinases (MMP) to degrade components of the extracellular matrix and their involvement in pathology-related processes of tissue remodeling, they were recently reported to enhance inflammation by activation of proinflammatory cytokines, or their release from the cell surface. In the work reported here, proteolytic activity previously found for hydatid cysts was further characterized as MMP-9. Active host MMP-9 was found in walls and fluids of bovine hydatid cysts of Echinococcus granulosus in the environment of granulomatous reaction. Pooled walls and fluids of hydatid cysts obtained from infected cattle were processed. Strong proteolytic activity was detected by zymography. The proteolytic fraction was purified by anion exchange and gelatin-agarose affinity chromatography. Major proteinases of the purified fraction were subjected to mass spectrometry and their identities were further confirmed by Western blotting using commercial anti-human MMP-9 monoclonal antibodies. Two proteinases were characterized as latent and active forms of host MMP-9. Using the same antibody for immunoblot, activity was localized, in paraffin-embedded sections of the parasite and the local host environment, to epithelioid and giant multinucleated cells. It is proposed here that MMP-9 is secreted by specialized host cells of monocytic lineage (epithelioid/giant cells) as an effector, in an attempt to digest the persistent foreign body. In vivo activation of MMP-9 suggests its involvement in inflammatory reaction and in the chemotaxis of inflammatory cells to the cyst. However, E. granulosus can deal efficiently with MMP-9. Research is suggested into possible immune evasion mechanisms, including the secretion of an inhibitory molecule.

  8. Holographic imaging with single pixel sensor

    NASA Astrophysics Data System (ADS)

    Leportier, Thibault; Lee, Young Tack; Hwang, Do Kyung; Park, Min-Chul

    2016-09-01

    Imaging techniques based on CCD sensors presenting very high number of pixels enable to record images with high resolution. However, the huge storage load and high bandwidth required to store and transmit digital holographic information are technical bottlenecks that should be overcome for the future of holographic display. Techniques to capture images with single pixel sensors have been greatly improved recently with the development of compressive sensing algorithm (CS). Since interference patterns may be considered sparse, the number of measurements required to recover the information with CS is lower than the number of pixels of the reconstructed image. In addition, this method does not need any scanning system. One other advantage of single pixel imaging is that the cost of recording system can be dramatically reduced since high-resolution cameras are expensive while compressive sensing exploits only one pixel. In this paper, we present an imaging system based on phase-shifting holography. First, simulations were performed to confirm that hologram could be reconstructed by compressive sensing even if the number of measurements was smaller than the number of pixels. Then, experimental set-up was realized. Several holograms with different phase shifts introduced by quarter and half wave plates in the reference beam were acquired. We demonstrated that our system enables the reconstruction of the object.

  9. Simulation study of pixel detector charge digitization

    NASA Astrophysics Data System (ADS)

    Wang, Fuyue; Nachman, Benjamin; Sciveres, Maurice; Lawrence Berkeley National Laboratory Team

    2017-01-01

    Reconstruction of tracks from nearly overlapping particles, called Tracking in Dense Environments (TIDE), is an increasingly important component of many physics analyses at the Large Hadron Collider as signatures involving highly boosted jets are investigated. TIDE makes use of the charge distribution inside a pixel cluster to resolve tracks that share one of more of their pixel detector hits. In practice, the pixel charge is discretized using the Time-over-Threshold (ToT) technique. More charge information is better for discrimination, but more challenging for designing and operating the detector. A model of the silicon pixels has been developed in order to study the impact of the precision of the digitized charge distribution on distinguishing multi-particle clusters. The output of the GEANT4-based simulation is used to train neutral networks that predict the multiplicity and location of particles depositing energy inside one cluster of pixels. By studying the multi-particle cluster identification efficiency and position resolution, we quantify the trade-off between the number of ToT bits and low-level tracking inputs. As both ATLAS and CMS are designing upgraded detectors, this work provides guidance for the pixel module designs to meet TIDE needs. Work funded by the China Scholarship Council and the Office of High Energy Physics of the U.S. Department of Energy under contract DE-AC02-05CH11231.

  10. Steganography based on pixel intensity value decomposition

    NASA Astrophysics Data System (ADS)

    Abdulla, Alan Anwar; Sellahewa, Harin; Jassim, Sabah A.

    2014-05-01

    This paper focuses on steganography based on pixel intensity value decomposition. A number of existing schemes such as binary, Fibonacci, Prime, Natural, Lucas, and Catalan-Fibonacci (CF) are evaluated in terms of payload capacity and stego quality. A new technique based on a specific representation is proposed to decompose pixel intensity values into 16 (virtual) bit-planes suitable for embedding purposes. The proposed decomposition has a desirable property whereby the sum of all bit-planes does not exceed the maximum pixel intensity value, i.e. 255. Experimental results demonstrate that the proposed technique offers an effective compromise between payload capacity and stego quality of existing embedding techniques based on pixel intensity value decomposition. Its capacity is equal to that of binary and Lucas, while it offers a higher capacity than Fibonacci, Prime, Natural, and CF when the secret bits are embedded in 1st Least Significant Bit (LSB). When the secret bits are embedded in higher bit-planes, i.e., 2nd LSB to 8th Most Significant Bit (MSB), the proposed scheme has more capacity than Natural numbers based embedding. However, from the 6th bit-plane onwards, the proposed scheme offers better stego quality. In general, the proposed decomposition scheme has less effect in terms of quality on pixel value when compared to most existing pixel intensity value decomposition techniques when embedding messages in higher bit-planes.

  11. Focal plane array with modular pixel array components for scalability

    SciTech Connect

    Kay, Randolph R; Campbell, David V; Shinde, Subhash L; Rienstra, Jeffrey L; Serkland, Darwin K; Holmes, Michael L

    2014-12-09

    A modular, scalable focal plane array is provided as an array of integrated circuit dice, wherein each die includes a given amount of modular pixel array circuitry. The array of dice effectively multiplies the amount of modular pixel array circuitry to produce a larger pixel array without increasing die size. Desired pixel pitch across the enlarged pixel array is preserved by forming die stacks with each pixel array circuitry die stacked on a separate die that contains the corresponding signal processing circuitry. Techniques for die stack interconnections and die stack placement are implemented to ensure that the desired pixel pitch is preserved across the enlarged pixel array.

  12. The Gas Pixel Detector as a solar X-ray polarimeter and imager

    NASA Astrophysics Data System (ADS)

    Fabiani, Sergio; Bellazzini, Ronaldo; Brez, Alessandro; di Cosimo, Sergio; Lazzarotto, Francesco; Muleri, Fabio; Rubini, Alda; Soffitta, Paolo; Spandre, Gloria

    The sun is the nearest astrophysical source with an interesting emission in the X-ray band. The study of energetic events, such as solar flares, can help us to understand the behaviour of the magnetic field of our star. There are in literature numerous studies published about polarization predictions, for a wide range of solar flare models. All these models involve emission from thermal and/or nonthermal processes. Furthermore, results of flare observations in the X-ray band have never been exhaustive. We want to present a new kind of instrument with polarimetric and imaging capabilities in the X-ray band. This instrument is the Gas Pixel Detector (GPD). It has been developed by the INFN and the IASF-Roma / INAF Italian research institutes. The GPD was born to achieve X-ray polarimetric measurements as well as X-ray images for astrophysical sources. It has a good spectroscopic sensitivity thanks to an energy resolution of some per cent and it allows also to perform timing measurements. Differently from all the other kinds of today's polarimeters, it doesn't need rotation! The GPD exploits the dependence of photoelectric cross section to photon polarization direction to the aim of measuring polarization. This instrument is essentially a ionization chamber: a cell filled by gas into which radiation enters through a window of 1.5 cm x 1.5 cm. The cell has a depth of some centimeters: typically from 1 to 2 cm. Every time that a photon is absorbed by the gas, a photoelectron is emitted with more probability in the direction of the electric vector of the photon absorbed. The photoelectron propagates and produces a track of ionization that is drifted, amplified and actually collected on a fine sub-divided pixeled detector, whose pixels have a dimension of 50 µm. At the present the chip integrates more than 16.5 millions of transistors. It has an active area of 105600 pixels organized in a honeycomb matrix 300x352. It is a self triggered system able to select itself the

  13. 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.

  14. 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.

  15. 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.

  16. Components of the Human SWI/SNF Complex Are Enriched in Active Chromatin and Are Associated with the Nuclear Matrix

    PubMed Central

    Reyes, Jose C.; Muchardt, Christian; Yaniv, Moshe

    1997-01-01

    Biochemical and genetic evidence suggest that the SWI/SNF complex is involved in the remodeling of chromatin during gene activation. We have used antibodies specific against three human subunits of this complex to study its subnuclear localization, as well as its potential association with active chromatin and the nuclear skeleton. Immunofluorescence studies revealed a punctate nuclear labeling pattern that was excluded from the nucleoli and from regions of condensed chromatin. Dual labeling failed to reveal significant colocalization of BRG1 or hBRM proteins with RNA polymerase II or with nuclear speckles involved in splicing. Chromatin fractionation experiments showed that both soluble and insoluble active chromatin are enriched in the hSWI/SNF proteins as compared with bulk chromatin. hSWI/SNF proteins were also found to be associated with the nuclear matrix or nuclear scaffold, suggesting that a fraction of the hSWI/SNF complex could be involved in the chromatin organization properties associated with matrix attachment regions. PMID:9128241

  17. Novel inhibitors of urokinase-type plasminogen activator and matrix metalloproteinase expression in metastatic cancer cell lines.

    PubMed

    Cakarovski, Kristina; Leung, Jenny Y; Restall, Christina; Carin-Carlson, Anna; Yang, Eunice; Perlmutter, Patrick; Anderson, Robin; Medcalf, Robert; Dear, Anthony E

    2004-07-01

    The plasminogen-activating (PA) and matrix metalloproteinase (MMP) enzyme systems are implicated in proteolytic turnover of the extracellular matrix (ECM) associated with biologic processes including wound healing, inflammation and angiogenesis. Aberrant expression of components of the PA and MMP enzyme systems occurs in the pathogenesis of metastatic cancer. Oxamflatin (Ox), a novel hydroxamic acid derivative, inhibits u-PA mRNA expression and proteolytic activity while simultaneously upregulating the expression of the natural inhibitor of u-PA, plasminogen activator inhibitor type 2 (PAI-2) in metastatic cancer cells. We have characterized the effects of Ox and a novel derivative, Metacept-1 (MCT-1), on PA and MMP-mediated proteolysis and invasion in several metastatic tumor lines. Both compounds are able to inhibit u-PA-, MMP-2- and MMP-9-mediated gene expression at low micromolar concentrations as well as u-PA- and MMP-mediated proteolysis as assessed by zymography, with MCT-1 being the more effective of the 2 agents in some assays. Cellular invasion assays correlate with gene expression and zymography experiments identifying both Ox and MCT-1 as able to inhibit invasion of metastatic cancer cell lines through matrigel at nanomolar concentrations, with MCT-1 more effective than Ox in 2 of the 3 cancer cell lines assessed.

  18. Synchrotron beam test of a photon counting pixel prototype based on Double-SOI technology

    NASA Astrophysics Data System (ADS)

    Zhou, Y.; Lu, Y.; Hashimoto, R.; Nishimura, R.; Kishimoto, S.; Arai, Y.; Ouyang, Q.

    2017-01-01

    The overall noise performances and first synchrotron beam measurement results of CPIXETEG3b, the first counting type Silicon-On-Insulator (SOI) pixel sensor prototype without crosstalk issue, are reported. The prototype includes a 64 × 64 pixel matrix with 50 μm pitch size. Each pixel consists of an N-in-P charge collection diode, a charge sensitive preamplifier, a shaper, a discriminator with thresholds adjustable by an in-pixel 4-bit DAC, and a 6-bit counter. The study was performed using the beam line 14A at KEK Photon Factory (KEK-PF) . The homogeneous response of the prototype, including charging-sharing effects between pixels were studied. 16 keV and 8 keV monochromatic small size (~ 10 μm diameter) X-ray beams were used for the charge sharing study, and a flat-field was added for homogenous response investigation. The overall detector homogeneity and the influence of basic detector parameters on charge sharing between pixels has been investigated.

  19. Effect of pixel resolution on texture features of breast masses in mammograms.

    PubMed

    Rangayyan, Rangaraj M; Nguyen, Thanh M; Ayres, Fábio J; Nandi, Asoke K

    2010-10-01

    The effect of pixel resolution on texture features computed using the gray-level co-occurrence matrix (GLCM) was analyzed in the task of discriminating mammographic breast lesions as benign masses or malignant tumors. Regions in mammograms related to 111 breast masses, including 65 benign masses and 46 malignant tumors, were analyzed at pixel sizes of 50, 100, 200, 400, 600, 800, and 1,000 μm. Classification experiments using each texture feature individually provided accuracy, in terms of the area under the receiver operating characteristics curve (AUC), of up to 0.72. Using the Bayesian classifier and the leave-one-out method, the AUC obtained was in the range 0.73 to 0.75 for the pixel resolutions of 200 to 800 μm, with 14 GLCM-based texture features using adaptive ribbons of pixels around the boundaries of the masses. Texture features computed using the ribbons resulted in higher classification accuracy than the same features computed using the corresponding regions within the mass boundaries. The t test was applied to AUC values obtained using 100 repetitions of random splitting of the texture features from the ribbons of masses into the training and testing sets. The texture features computed with the pixel size of 200 μm provided the highest average AUC with statistically highly significant differences as compared to all of the other pixel sizes tested, except 100 μm.

  20. Hexagonal Pixels and Indexing Scheme for Binary Images

    NASA Technical Reports Server (NTRS)

    Johnson, Gordon G.

    2004-01-01

    A scheme for resampling binaryimage data from a rectangular grid to a regular hexagonal grid and an associated tree-structured pixel-indexing scheme keyed to the level of resolution have been devised. This scheme could be utilized in conjunction with appropriate image-data-processing algorithms to enable automated retrieval and/or recognition of images. For some purposes, this scheme is superior to a prior scheme that relies on rectangular pixels: one example of such a purpose is recognition of fingerprints, which can be approximated more closely by use of line segments along hexagonal axes than by line segments along rectangular axes. This scheme could also be combined with algorithms for query-image-based retrieval of images via the Internet. A binary image on a rectangular grid is generated by raster scanning or by sampling on a stationary grid of rectangular pixels. In either case, each pixel (each cell in the rectangular grid) is denoted as either bright or dark, depending on whether the light level in the pixel is above or below a prescribed threshold. The binary data on such an image are stored in a matrix form that lends itself readily to searches of line segments aligned with either or both of the perpendicular coordinate axes. The first step in resampling onto a regular hexagonal grid is to make the resolution of the hexagonal grid fine enough to capture all the binaryimage detail from the rectangular grid. In practice, this amounts to choosing a hexagonal-cell width equal to or less than a third of the rectangular- cell width. Once the data have been resampled onto the hexagonal grid, the image can readily be checked for line segments aligned with the hexagonal coordinate axes, which typically lie at angles of 30deg, 90deg, and 150deg with respect to say, the horizontal rectangular coordinate axis. Optionally, one can then rotate the rectangular image by 90deg, then again sample onto the hexagonal grid and check for line segments at angles of 0deg, 60deg

  1. The matrix metalloproteinase gene GmMMP2 is activated in response to pathogenic infections in soybean.

    PubMed

    Liu, Y; Dammann, C; Bhattacharyya, M K

    2001-12-01

    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.

  2. Targeted SPECT/CT Imaging of Matrix Metalloproteinase Activity in the Evaluation of Remodeling Tissue-Engineered Vascular Grafts Implanted in a Growing Lamb Model

    PubMed Central

    Stacy, Mitchel R.; Naito, Yuji; Maxfield, Mark W.; Kurobe, Hirotsugu; Tara, Shuhei; Chan, Chung; Rocco, Kevin A.; Shinoka, Toshiharu; Sinusas, Albert J.; Breuer, Christopher K.

    2014-01-01

    Objective(s) The clinical translation of tissue-engineered vascular grafts has been demonstrated in children. The remodeling of biodegradable, cell-seeded scaffolds to functional neovessels is partially attributed to matrix metalloproteinases. Noninvasive assessment of matrix metalloproteinase activity may indicate graft remodeling and elucidate the progression of neovessel formation. Therefore, matrix metalloproteinase activity was evaluated in grafts implanted in lambs using in vivo and ex vivo hybrid imaging. Graft growth and remodeling was quantified using in vivo X-ray computed tomography angiography. Methods Cell-seeded and unseeded scaffolds were implanted in lambs (n=5) as inferior vena cava interposition grafts. At 2 and 6 months post-implantation, in vivo angiography assessed graft morphology. In vivo and ex vivo single photon emission tomography/X-ray computed tomography imaging was performed with a radiolabeled compound targeting matrix metalloproteinase activity at 6 months. Neotissue was examined at 6 months using qualitative histologic and immunohistochemical staining and quantitative biochemical analysis. Results Seeded grafts demonstrated significant luminal and longitudinal growth from 2 to 6 months. In vivo imaging revealed subjectively higher matrix metalloproteinase activity in grafts vs. native tissue. Ex vivo imaging confirmed a quantitative increase in matrix metalloproteinase activity and demonstrated higher activity in unseeded vs. seeded grafts. Glycosaminoglycan content was increased in seeded grafts vs. unseeded grafts, without significant differences in collagen content. Conclusions Matrix metalloproteinase activity remains elevated in tissue-engineered grafts 6 months post-implantation and may indicate remodeling. Optimization of in vivo imaging to noninvasively evaluate matrix metalloproteinase activity may assist in serial assessment of vascular graft remodeling. PMID:24952823

  3. Mueller-matrix ellipsometry studies of optically active structures in scarab beetles

    NASA Astrophysics Data System (ADS)

    Järrendahl, K.; Landin, J.; Arwin, H.

    2010-06-01

    The complexity of multilayers, photonic crystals, metamaterials and other artificial materials has promoted the use of spectroscopic, variable angle, generalized and Mueller-matrix ellipsometry. Naturally occurring structures may show even higher complexity than artificial structures but with a more narrow range of constituent materials. Fascinating reflection properties result from intricate photonic structures in, for instance, the wing scales and cuticles of insects. Currently there is a large interest to explore such functional supramolecular architectures for exploitation in nanotechnology. In this study, Mueller-matrix spectroscopic ellipsometry is applied in the spectral range of 250 to 1000 nm to investigate optical response and structures of the cuticle of Scarab beetles of the Cetoniinae subfamily. The cuticle of Cetonia aurata (the rose chafer, la cétoine dorée) is green with a metallic appearance and reflects left-handed circular/elliptically polarized light. It has been suggested that the polarization of this metallic gloss is caused by a helical structure in the chitinous cuticle. We find that the polarization effect is limited to the narrow spectral range 470-550 nm whereas for shorter or longer wavelengths the reflection properties are similar to those from a near-dielectric material. Model calculations and parameterization of the nanostructure employing a heliocoidal structure are discussed. As a comparison the polarization effects from light reflected from two other beetles will be presented. Coptomia laevis has a similar appearance as Cetonia aurata but has very different polarization properties. The golden Plusiotis argentiola has very interesting properties showing both left and right-handed polarization depending on incidence angle and wavelength.

  4. Wnt-3a-activated human fibroblasts promote human keratinocyte proliferation and matrix destruction.

    PubMed

    Sobel, Katrin; Tham, Marius; Stark, Hans-Jürgen; Stammer, Hermann; Prätzel-Wunder, Silke; Bickenbach, Jackie R; Boukamp, Petra

    2015-06-15

    Aberrant Wnt regulation, detectable by nuclear translocation of beta-catenin, is a hallmark of many cancers including skin squamous cell carcinomas (SCCs). By analyzing primary human skin SCCs, we demonstrate that nuclear beta-catenin is not restricted to SCC cells but also detected in stromal fibroblasts, suggesting an important role for aberrant Wnt regulation also in the tumor microenvironment. When human keratinocytes and fibroblasts were treated with Wnt-3a, fibroblasts proved to be more responsive. Accordingly, Wnt-3a did not alter HaCaT cell functions in a cell-autonomous manner. However, when organotypic cultures (OTCs) were treated with Wnt-3a, HaCaT keratinocytes responded with increased proliferation. As nuclear beta-catenin was induced only in the fibroblasts, this argued for a Wnt-dependent, paracrine keratinocyte stimulation. Global gene expression analysis of Wnt-3a-stimulated fibroblasts identified genes encoding interleukin-8 (IL-8) and C-C motif chemokine 2 (CCL-2) as well as matrix metalloproteinase-1 (MMP-1) as Wnt-3a targets. In agreement, we show that IL-8 and CCL-2 were secreted in high amounts by Wnt-3a-stimulated fibroblasts also in OTCs. The functional role of IL-8 and CCL-2 as keratinocyte growth regulators was confirmed by directly stimulating HaCaT cell proliferation in conventional cultures. Most important, neutralizing antibodies against IL-8 and CCL-2 abolished the Wnt-dependent HaCaT cell hyperproliferation in OTCs. Additionally, MMP-1 was expressed in high amounts in Wnt-3a-stimulated OTCs and degraded the stromal matrix. Thus, our data show that Wnt-3a stimulates fibroblasts to secrete both keratinocyte proliferation-inducing cytokines and stroma-degrading metalloproteinases, thereby providing evidence for a novel Wnt deregulation in the tumor-stroma directly contributing to skin cancer progression.

  5. Novel nuclear matrix protein HET binds to and influences activity of the HSP27 promoter in human breast cancer cells.

    PubMed

    Oesterreich, S; Lee, A V; Sullivan, T M; Samuel, S K; Davie, J R; Fuqua, S A

    1997-11-01

    Since the small heat shock protein hsp27 enhances both growth and drug resistance in breast cancer cells, and is a bad prognostic factor in certain subsets of breast cancer patients, we have characterized the transcriptional regulation of hsp27, with the long-term goal of targeting its expression clinically. The majority of the promoter activity resides in the most proximal 200 bp. This region contains an imperfect estrogen response element (ERE) that is separated by a 13-bp spacer that contains a TATA box. Gel-shift analysis revealed the binding of a protein (termed HET for Hsp27-ERE-TATA-binding protein) to this region that was neither the estrogen receptor nor TATA-binding protein. We cloned a complete cDNA (2.9 kb) for HET from an MCF-7 cDNA library. To confirm the identity of the HET clone, we expressed a partial HET clone as a glutathione S-transferase fusion protein, and showed binding to the hsp27 promoter fragment in gel-retardation assays. The HET clone is almost identical to a recently published scaffold attachment factor (SAF-B) cloned from a HeLa cell cDNA library. Scaffold attachment factors are a subset of nuclear matrix proteins (NMP) that interact with matrix attachment regions. Analyzing how HET could act as a regulator of hsp27 transcription and as a SAF/NMP, we studied its subnuclear localization and its effect on hsp27 transcription in human breast cancer cells. We were able to show that HET is localized in the nuclear matrix in various breast cancer cell lines. Furthermore, in transient transfection assays using hsp27 promoter-luciferase reporter constructs, HET overexpression resulted in a dose-dependent decrease of hsp27 promoter activity in several cell lines.

  6. Spatial clustering of pixels of a multispectral image

    DOEpatents

    Conger, James Lynn

    2014-08-19

    A method and system for clustering the pixels of a multispectral image is provided. A clustering system computes a maximum spectral similarity score for each pixel that indicates the similarity between that pixel and the most similar neighboring. To determine the maximum similarity score for a pixel, the clustering system generates a similarity score between that pixel and each of its neighboring pixels and then selects the similarity score that represents the highest similarity as the maximum similarity score. The clustering system may apply a filtering criterion based on the maximum similarity score so that pixels with similarity scores below a minimum threshold are not clustered. The clustering system changes the current pixel values of the pixels in a cluster based on an averaging of the original pixel values of the pixels in the cluster.

  7. PPARα and PPARγ attenuate HIV-induced dysregulation of tight junction proteins by modulations of matrix metalloproteinase and proteasome activities

    PubMed Central

    Huang, Wen; Eum, Sung Yong; András, Ibolya E; Hennig, Bernhard; Toborek, Michal

    2009-01-01

    The blood-brain barrier (BBB) plays an important role in HIV trafficking into the brain and the development of the central nervous system complications in HIV infection. Tight junctions are the main structural and functional elements that regulate the BBB integrity. Exposure of human brain microvascular endothelial cells (hCMEC/D3 cell line) to HIV-infected monocytes resulted in decreased expression of tight junction proteins, such as junctional adhesion molecule-A (JAM)-A, occludin, and zonula occludens (ZO)-1. Control experiments involved exposure to uninfected monocytes. Alterations of tight junction protein expression were associated with increased endothelial permeability and elevated transendothelial migration of HIV-infected monocytes across an in vitro model of the BBB. Notably, overexpression of the peroxisome proliferator-activated receptor (PPAR)α or PPARγ attenuated HIV-mediated dysregulation of tight junction proteins. With the use of exogenous PPARγ agonists and silencing of PPARα or PPARγ, these protective effects were connected to down-regulation of matrix metalloproteinase (MMP) and proteasome activities. Indeed, the HIV-induced decrease in the expression of JAM-A and occludin was restored by inhibition of MMP activity. Moreover, both MMP and proteasome inhibitors attenuated HIV-mediated altered expression of ZO-1. The present data indicate that down-regulation of MMP and proteasome activities constitutes a novel mechanism of PPAR-induced protections against HIV-induced disruption of brain endothelial cells.—Huang, W., Eum, S. Y., András, I. E., Hennig, B., Toborek, M. PPARα and PPARγ attenuate HIV-induced dysregulation of tight junction proteins by modulations of matrix metalloproteinase and proteasome activities. PMID:19141539

  8. Expression of membrane-type 1 matrix metalloproteinase and activation of progelatinase A in human osteoarthritic cartilage.

    PubMed Central

    Imai, K.; Ohta, S.; Matsumoto, T.; Fujimoto, N.; Sato, H.; Seiki, M.; Okada, Y.

    1997-01-01

    Matrix metalloproteinases (MMPs) are expressed in osteoarthritic (OA) cartilage and are thought to be involved in the degradation of cartilage extracellular matrix (ECM). Among these proteinases, MMP-2 (gelatinase A) demonstrates a wide range of substrate specificity against the ECM present in cartilage. Although MMP-2 expression increases in OA cartilage, the activation mechanism of the corresponding zymogen (pro-MMP-2) in cartilage is unknown. In this study, we examined the expression pattern of membrane-type 1 MMP (MT1-MMP) in human OA articular cartilage and its correlation with the activation of pro-MMP-2. Immunohistochemical studies demonstrate that MT1-MMP localizes to the chondrocytes in the superficial and transitional zones in all of the samples examined directly correlating with cartilage degradation. Reverse transcription polymerase chain reaction confirmed the predominant expression of MT1-MMP mRNA in the OA cartilage. In situ hybridization revealed the site of expression of MT1-MMP in OA cartilage to be the chondrocytes. Through gelatin zymography and a sandwich enzyme immunoassay it was demonstrated that OA cartilage explants secrete significantly higher levels of pro-MMP-2 than normal samples. Pro-MMP-2 activation was enhanced in the OA cartilage samples and correlated with MT1-MMP expression in the cartilage. Plasma membranes prepared from cultured chondrocytes with MT1-MMP expression and those directly isolated from OA cartilage could activate pro-MMP-2. MT1-MMP gene expression in cultured chondrocytes was induced by treatment with interleukin-1 alpha and/or tumor necrosis factor-alpha. These data suggest that cytokine-induced MT1-MMP in the chondrocytes may play a key role in the activation of pro-MMP-2 in the OA articular cartilage, leading to cartilage destruction through ECM degradation. Images Figure 1 Figure 3 Figure 4 Figure 5 Figure 7 Figure 8 PMID:9212749

  9. 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.

  10. The influence of opioid peptides on matrix metalloproteinase-9 and urokinase plasminogen activator expression in three cancer cell lines.

    PubMed

    Gach, K; Wyrebska, A; Szemraj, J; Janecka, A

    2012-01-01

    Matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA) regulate proteolysis of the extracellular matrix (ECM) and as a consequence are involved in a number of physiological and pathological states, including cancer. A crucial feature of cancer progression and metastasis is the disruption of the ECM and spreading of proliferating cancer cells. Over-expression of MMPs and uPA is common for most types of cancers and correlates well with the adverse prognosis. Compounds able to modulate the activity of these proteolytic enzymes may become important agents in cancer therapy. In the present study, we examined the effect of the mu-opioid receptor selective peptide, morphiceptin, and its two synthetic analogs on mRNA and protein levels of MMP-9 and uPA in three human cancer cell lines: MCF-7, HT-29, and SH-SY5Y. Our findings indicate that in all three cell lines morphiceptin and its analogs attenuated MMP-9 expression and secretion and that this effect is not mediated by opioid receptors but is under control of the nitric oxide system. On the other hand, tested opioids up-regulated uPA levels through a mechanism that involved opioid-receptors. Different pathways by which opioid peptides exert their actionin cancer cells can explain their contradictory influence on the level of cancer markers.

  11. DETECTORS AND EXPERIMENTAL METHODS: Study of the characteristics of a scintillation array and single pixels for nuclear medicine imaging applications

    NASA Astrophysics Data System (ADS)

    Zhu, Jie; Ma, Hong-Guang; Ma, Wen-Yan; Zeng, Hui; Wang, Zhao-Min; Xu, Zi-Zong

    2009-04-01

    By using a pixelized Nal(Tl) crystal array coupled to a R2486 PSPMT, the characteristics of the array and of a single pixel, such as the light output, energy resolution, peak-to-valley ratio (P/V) and imaging performance of the detector were studied. The pixel size of the NaI(TI) scintillation pixel array is 2 mm×2 mm×5 mm. There are in total 484 pixels in a 22 × 22 matrix. In the pixel spectrum an average peak-to-valley ratio (P/V) of 16 was obtained. In the image of all the pixels, good values for the Peak-to-Valley ratios could be achieved, namely a mean of 17, a maximum of 45 and the average peak FWHM (the average value of intrinsic spatial resolution) of 2.3 mm. However, the PSPMT non-uniform response and the scintillation pixels array inhomogeneities degrade the imaging performance of the detector.

  12. Hydrogen sulfide inhibits high glucose-induced matrix protein synthesis by activating AMP-activated protein kinase in renal epithelial cells.

    PubMed

    Lee, Hak Joo; Mariappan, Meenalakshmi M; Feliers, Denis; Cavaglieri, Rita C; Sataranatarajan, Kavithalakshmi; Abboud, Hanna E; Choudhury, Goutam Ghosh; Kasinath, Balakuntalam S

    2012-02-10

    Hydrogen sulfide, a signaling gas, affects several cell functions. We hypothesized that hydrogen sulfide modulates high glucose (30 mm) stimulation of matrix protein synthesis in glomerular epithelial cells. High glucose stimulation of global protein synthesis, cellular hypertrophy, and matrix laminin and type IV collagen content was inhibited by sodium hydrosulfide (NaHS), an H(2)S donor. High glucose activation of mammalian target of rapamycin (mTOR) complex 1 (mTORC1), shown by phosphorylation of p70S6 kinase and 4E-BP1, was inhibited by NaHS. High glucose stimulated mTORC1 to promote key events in the initiation and elongation phases of mRNA translation: binding of eIF4A to eIF4G, reduction in PDCD4 expression and inhibition of its binding to eIF4A, eEF2 kinase phosphorylation, and dephosphorylation of eEF2; these events were inhibited by NaHS. The role of AMP-activated protein kinase (AMPK), an inhibitor of protein synthesis, was examined. NaHS dose-dependently stimulated AMPK phosphorylation and restored AMPK phosphorylation reduced by high glucose. Compound C, an AMPK inhibitor, abolished NaHS modulation of high glucose effect on events in mRNA translation as well as global and matrix protein synthesis. NaHS induction of AMPK phosphorylation was inhibited by siRNA for calmodulin kinase kinase β, but not LKB1, upstream kinases for AMPK; STO-609, a calmodulin kinase kinase β inhibitor, had the same effect. Renal cortical content of cystathionine β-synthase and cystathionine γ-lyase, hydrogen sulfide-generating enzymes, was significantly reduced in mice with type 1 diabetes or type 2 diabetes, coinciding with renal hypertrophy and matrix accumulation. Hydrogen sulfide is a newly identified modulator of protein synthesis in the kidney, and reduction in its generation may contribute to kidney injury in diabetes.

  13. Modulation of matrix metalloproteinase-9 activity by hyaluronan is dependent on NF-kappaB activity in lymphoma cell lines with dissimilar invasive behavior.

    PubMed

    Alaniz, Laura; García, Mariana; Cabrera, Paula; Arnaiz, María; Cavaliere, Victoria; Blanco, Guillermo; Alvarez, Elida; Hajos, Silvia

    2004-11-12

    Expression and activity of matrix metalloproteinase-9 (MMP-9) as well as its relationship with hyaluronan (HA) and NF-kappaB activity were analyzed in two murine lymphoma cell lines with dissimilar migration and invasive behavior. MMP activity was evaluated by zymograms in supernatants, membrane extracts of tumor cells, and in the organs invaded by these cells. The more aggressive LBLa cell line showed MMP-9 activity in vitro, which increased after HA treatment and was blocked by anti-CD44 mAb. Such activity was not found in the less aggressive LBLc. MMP-9 and MMP-2 activity was found in organs invaded by both cell lines, although differential MMP-9 activity was observed in lung infiltrated only by LBLa cell line. NF-kappaB activation was evaluated to determine whether differential activity of MMP-9 was dependent on downstream signaling pathway, showing higher NF-kappaB activity in the more aggressive LBLa cell line. Our results showed that MMP-9 activity modulated by HA through NF-kappaB signaling pathway may be involved in the aggressive behavior of LBLa.

  14. A matrix-focused structure-activity and binding site flexibility study of quinolinol inhibitors of botulinum neurotoxin serotype A.

    PubMed

    Harrell, William A; Vieira, Rebecca C; Ensel, Susan M; Montgomery, Vicki; Guernieri, Rebecca; Eccard, Vanessa S; Campbell, Yvette; Roxas-Duncan, Virginia; Cardellina, John H; Webb, Robert P; Smith, Leonard A

    2017-02-01

    Our initial discovery of 8-hydroxyquinoline inhibitors of BoNT/A and separation/testing of enantiomers of one of the more active leads indicated considerable flexibility in the binding site. We designed a limited study to investigate this flexibility and probe structure-activity relationships; utilizing the Betti reaction, a 36 compound matrix of quinolinol BoNT/A LC inhibitors was developed using three 8-hydroxyquinolines, three heteroaromatic amines, and four substituted benzaldehydes. This study has revealed some of the most effective quinolinol-based BoNT/A inhibitors to date, with 7 compounds displaying IC50 values ⩽1μM and 11 effective at ⩽2μM in an ex vivo assay.

  15. Testing the toxicity of influents to activated sludge plants with the Vibrio fischeri bioassay utilising a sludge matrix.

    PubMed

    Hoffmann, C; Christofi, N

    2001-10-01

    To protect the bioceonosis within activated sludge, a method of predicting the toxic effect of influents to the biological treatment stage of waste water treatment plants, based on DIN method 38412 L 34, has been developed. A population of the luminescent marine bacterium Vibrio fischeri was incorporated into a sludge testing matrix derived from a model laboratory and real activated sludge plants. The sludge was challenged with different concentrations of pure toxicants and complex aqueous samples, and light output by V. fischeri monitored. The results were compared to toxicant testing in the absence of sludge (standard test). The modified method was found to be less sensitive for some toxicants tested than the standard DIN and other bioluminescent tests, but considered more realistic as it provides buffering and takes into account sorption which can affect the sensitivity of the test towards some compounds. The method is comparable in terms of ease of use, speed, reproducibility and cost effectiveness to standard V. fischeri luminescence methods.

  16. Development of the Continuous Acquisition Pixel (CAP) sensor for high luminosity lepton colliders

    NASA Astrophysics Data System (ADS)

    Varner, G.; Aihara, H.; Barbero, M.; Bozek, A.; Browder, T.; Hazumi, M.; Kennedy, J.; Martin, E.; Mueller, J.; Olsen, S.; Palka, H.; Rosen, M.; Ruckman, L.; Stanič, S.; Trabelsi, K.; Tsuboyama, T.; Uchida, K.; Yang, Q.; Yarema, R.

    2006-09-01

    A future higher luminosity B-factory detector and concept study detectors for the proposed International Linear Collider require precision vertex reconstruction while coping with high track densities and radiation exposures. Compared with current silicon strip and hybrid pixels, a significant reduction in the overall detector material thickness is needed to achieve the desired vertex resolution. Considerable progress in the development of thin CMOS-based Monolithic Active Pixel Sensors (MAPS) in recent years makes them a viable technology option and feasibility studies are being actively pursued. The most serious concerns are their radiation hardness and their readout speed. To address these, several prototypes denoted as the Continuous Acquisition Pixel (CAP) sensors have been developed and tested. The latest of the CAP sensor prototypes is CAP3, designed in the TSMC 0.25 μm process with a 5-deep Correlated Double Sample (CDS) pair pipeline in each pixel. A setup with several CAP3 sensors is under evaluation to assess the performance of a full-scale pixel readout system running at realistic readout speed. Given the similarity in the occupancy numbers and hit throughput requirements, per unit area, between a Belle vertex detector upgradation and the requirements for a future ILC pixel detector, this effort can be considered a small-scale functioning prototype for such a future system. The results and plans for the next stages of R&D towards a full Belle Pixel Vertex Detector (PVD) are presented.

  17. An estimation error bound for pixelated sensing

    NASA Astrophysics Data System (ADS)

    Kreucher, Chris; Bell, Kristine

    2016-05-01

    This paper considers the ubiquitous problem of estimating the state (e.g., position) of an object based on a series of noisy measurements. The standard approach is to formulate this problem as one of measuring the state (or a function of the state) corrupted by additive Gaussian noise. This model assumes both (i) the sensor provides a measurement of the true target (or, alternatively, a separate signal processing step has eliminated false alarms), and (ii) The error source in the measurement is accurately described by a Gaussian model. In reality, however, sensor measurement are often formed on a grid of pixels - e.g., Ground Moving Target Indication (GMTI) measurements are formed for a discrete set of (angle, range, velocity) voxels, and EO imagery is made on (x, y) grids. When a target is present in a pixel, therefore, uncertainty is not Gaussian (instead it is a boxcar function) and unbiased estimation is not generally possible as the location of the target within the pixel defines the bias of the estimator. It turns out that this small modification to the measurement model makes traditional bounding approaches not applicable. This paper discusses pixelated sensing in more detail and derives the minimum mean squared error (MMSE) bound for estimation in the pixelated scenario. We then use this error calculation to investigate the utility of using non-thresholded measurements.

  18. Mapping Electrical Crosstalk in Pixelated Sensor Arrays

    NASA Technical Reports Server (NTRS)

    Seshadri, S.; Cole, D. M.; Hancock, B. R.; Smith, R. M.

    2008-01-01

    Electronic coupling effects such as Inter-Pixel Capacitance (IPC) affect the quantitative interpretation of image data from CMOS, hybrid visible and infrared imagers alike. Existing methods of characterizing IPC do not provide a map of the spatial variation of IPC over all pixels. We demonstrate a deterministic method that provides a direct quantitative map of the crosstalk across an imager. The approach requires only the ability to reset single pixels to an arbitrary voltage, different from the rest of the imager. No illumination source is required. Mapping IPC independently for each pixel is also made practical by the greater S/N ratio achievable for an electrical stimulus than for an optical stimulus, which is subject to both Poisson statistics and diffusion effects of photo-generated charge. The data we present illustrates a more complex picture of IPC in Teledyne HgCdTe and HyViSi focal plane arrays than is presently understood, including the presence of a newly discovered, long range IPC in the HyViSi FPA that extends tens of pixels in distance, likely stemming from extended field effects in the fully depleted substrate. The sensitivity of the measurement approach has been shown to be good enough to distinguish spatial structure in IPC of the order of 0.1%.

  19. Sensor Development and Readout Prototyping for the STAR Pixel Detector

    SciTech Connect

    Greiner, L.; Anderssen, E.; Matis, H.S.; Ritter, H.G.; Stezelberger, T.; Szelezniak, M.; Sun, X.; Vu, C.; Wieman, H.

    2009-01-14

    The STAR experiment at the Relativistic Heavy Ion Collider (RHIC) is designing a new vertex detector. The purpose of this upgrade detector is to provide high resolution pointing to allow for the direct topological reconstruction of heavy flavor decays such as the D{sup 0} by finding vertices displaced from the collision vertex by greater than 60 microns. We are using Monolithic Active Pixel Sensor (MAPS) as the sensor technology and have a coupled sensor development and readout system plan that leads to a final detector with a <200 {micro}s integration time, 400 M pixels and a coverage of -1 < {eta} < 1. We present our coupled sensor and readout development plan and the status of the prototyping work that has been accomplished.

  20. Image pixel device using integrated organic electronic components

    NASA Astrophysics Data System (ADS)

    Swathi, K.; Narayan, K. S.

    2016-11-01

    We report a solution processed, monolithically integrated device similar to an imaging pixel element used in complementary metal-oxide semiconductor (CMOS) based cameras. This integrated pixel essentially consists of a pair of organic photodiode (OPD) and organic field effect transistor (OFET). The signal generated by the light responsive OPD drives the OFET to different output states to quantify the light intensity. The prerequisite of a low operating voltage OFET (<2 V) was achieved using a bottom-gate, top-contact OFET consisting of a high mobility polymer semiconductor and a self-assembled hybrid dielectric layer. A bulk heterojunction blend was used as the photo-active layer in the OPD along with suitable buffer layers for charge extraction. The material parameters were optimized to realize a suitable structure which clearly demonstrated the interplay of the OPD and OFET operations, thereby forming a roadmap for all-organic CMOS arrays.

  1. Measurement results of DIPIX pixel sensor developed in SOI technology

    NASA Astrophysics Data System (ADS)

    Ahmed, Mohammed Imran; Arai, Yasuo; Idzik, Marek; Kapusta, Piotr; Miyoshi, Toshinobu; Turala, Michal

    2013-08-01

    The development of integration type pixel detectors presents interest for physics communities because it brings optimization of design, simplicity of production-which means smaller cost, and reduction of detector material budget. During the last decade a lot of research and development activities took place in the field of CMOS Silicon-On-Insulator (SOI) technology resulting in improvement in wafer size, wafer resistivity and MIM capacitance. Several ideas have been tested successfully and are gradually entering into the application phase. Some of the novel concepts exploring SOI technology are pursued at KEK; several prototypes of dual mode integration type pixel (DIPIX) have been recently produced and described. This report presents initial test results of some of the prototypes including tests obtained with the infrared laser beams and Americium (Am-241) source. The Equivalent Noise Charge (ENC) of 86 e - has been measured. The measured performance demonstrates that SOI technology is a feasible choice for future applications.

  2. Matrix metalloproteinase 13 modulates intestinal epithelial barrier integrity in inflammatory diseases by activating TNF

    PubMed Central

    Vandenbroucke, Roosmarijn E; Dejonckheere, Eline; Van Hauwermeiren, Filip; Lodens, Sofie; De Rycke, Riet; Van Wonterghem, Elien; Staes, An; Gevaert, Kris; López-Otin, Carlos; Libert, Claude

    2013-01-01

    Several pathological processes, such as sepsis and inflammatory bowel disease (IBD), are associated with impairment of intestinal epithelial barrier. Here, we investigated the role of matrix metalloproteinase MMP13 in these diseases. We observed that MMP13−/− mice display a strong protection in LPS- and caecal ligation and puncture-induced sepsis. We could attribute this protection to reduced LPS-induced goblet cell depletion, endoplasmic reticulum stress, permeability and tight junction destabilization in the gut of MMP13−/− mice compared to MMP13+/+ mice. Both in vitro and in vivo, we found that MMP13 is able to cleave pro-TNF into bioactive TNF. By LC-MS/MS, we identified three MMP13 cleavage sites, which proves that MMP13 is an alternative TNF sheddase next to the TNF converting enzyme TACE. Similarly, we found that the same mechanism was responsible for the observed protection of the MMP13−/− mice in a mouse model of DSS-induced colitis. We identified MMP13 as an important mediator in sepsis and IBD via the shedding of TNF. Hence, we propose MMP13 as a novel drug target for diseases in which damage to the gut is essential. PMID:23723167

  3. Accelerated biodegradation of silk sutures through matrix metalloproteinase activation by incorporating 4-hexylresorcinol

    PubMed Central

    Jo, You-Young; Kweon, HaeYong; Kim, Dae-Won; Kim, Min-Keun; Kim, Seong-Gon; Kim, Jwa-Young; Chae, Weon-Sik; Hong, Sam-Pyo; Park, Young-Hwan; Lee, Si Young; Choi, Je-Yong

    2017-01-01

    Silk suture material is primarily composed of silk fibroin and regarded as a non-resorbable material. It is slowly degraded by proteolysis when it is implanted into the body. 4-Hexylresorcinol (4HR) is a well-known antiseptic. In this study, the biodegradability of 4HR-incorporated silk sutures were compared to that of untreated silk sutures and polyglactin 910 sutures, a commercially available resorbable suture. 4HR-incorporated silk sutures exhibited anti-microbial properties. Matrix metalloproteinase (MMP) can digest a wide spectrum of proteins. 4HR increased MMP-2, -3, and -9 expression in RAW264.7 cells. MMP-2, -3, and -9 were able to digest not only silk fibroin but also silk sutures. Consequently, 59.5% of the 4HR-incorporated silk suture material remained at 11 weeks after grafting, which was similar to that of polyglactin 910 degradation (56.4% remained). The residual amount of bare silk suture material at 11 weeks after grafting was 91.5%. The expression levels of MMP-2, -3 and -9 were high in the 4HR-incorporated silk suture-implanted site 12 weeks after implantation. In conclusion, 4HR-treated silk sutures exhibited anti-microbial properties and a similar level of bio-degradation to polyglactin 910 sutures and induced higher expression of MMP-2, -3, and -9 in macrophages. PMID:28205580

  4. Matrix Producing Cells in Chronic Kidney Disease: Origin, Regulation, and Activation.

    PubMed

    Kramann, Rafael; Dirocco, Derek P; Maarouf, Omar H; Humphreys, Benjamin D

    2013-12-01

    Chronic injury to the kidney causes kidney fibrosis with irreversible loss of functional renal parenchyma and leads to the clinical syndromes of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Regardless of the type of initial injury, kidney disease progression follows the same pathophysiologic processes characterized by interstitial fibrosis, capillary rarefaction and tubular atrophy. Myofibroblasts play a pivotal role in fibrosis by driving excessive extracellular matrix (ECM) deposition. Targeting these cells in order to prevent the progression of CKD is a promising therapeutic strategy, however, the cellular source of these cells is still controversial. In recent years, a growing amount of evidence points to resident mesenchymal cells such as pericytes and perivascular fibroblasts, which form extensive networks around the renal vasculature, as major contributors to the pool of myofibroblasts in renal fibrogenesis. Identifying the cellular origin of myofibroblasts and the key regulatory pathways that drive myofibroblast proliferation and transdifferentiation as well as capillary rarefaction is the first step to developing novel anti-fibrotic therapeutics to slow or even reverse CKD progression and ultimately reduce the prevalence of ESRD. This review will summarize recent findings concerning the cellular source of myofibroblasts and highlight recent discoveries concerning the key regulatory signaling pathways that drive their expansion and progression in CKD.

  5. Pixels, Blocks of Pixels, and Polygons: Choosing a Spatial Unit for Thematic Accuracy Assessment

    EPA Science Inventory

    Pixels, polygons, and blocks of pixels are all potentially viable spatial assessment units for conducting an accuracy assessment. We develop a statistical population-based framework to examine how the spatial unit chosen affects the outcome of an accuracy assessment. The populati...

  6. A MCM-D-type module for the ATLAS pixel detector

    SciTech Connect

    Becks, K.H.; Beyne, E.; Ehrmann, O.; Gerlach, P.; Gregor, I.M.; Pieters, P.; Toepper, M.; Truzzi, C.; Wolf, J.

    1999-12-01

    For the ATLAS experiment at the planned Large Hadron Collider LHC at CERN hybrid pixel detectors are being built as innermost layers of the inner tracking detector system. Modules are the basic building blocks of the ATLAS pixel detector. A module consists of a sensor tile with an active area of 16.4 mm x 60.4 mm, 16 read out IC's, each serving 24 x 160 pixel unit cells, a module controller chip, an optical transceiver and the local signal interconnection and power distribution busses. The dies are attached by flip-chip assembly to the sensor diodes and the local busses.

  7. Monolithic integration of individually addressable light-emitting diode color pixels

    NASA Astrophysics Data System (ADS)

    Chung, Kunook; Sui, Jingyang; Demory, Brandon; Teng, Chu-Hsiang; Ku, Pei-Cheng

    2017-03-01

    Monolithic integration of individually addressable light-emitting diode (LED) color pixels is reported. The integration is enabled by local strain engineering. The use of a nanostructured active region comprising one or more nanopillars allows color tuning across the visible spectrum. In the current work, integration of amber, green, and blue pixels is demonstrated. The nanopillar LEDs exhibit an electrical performance comparable to that of a conventional thin-film LED fabricated on the same wafer. The proposed platform uses only standard epitaxy and a similar process flow as a conventional LED. It is also shown that the emission intensity can be linearly tuned without shifting the color coordinate of individual pixels.

  8. Detection of active matrix metalloproteinase-3 in serum and fibroblast-like synoviocytes of collagen-induced arthritis mice.

    PubMed

    Lee, Aeju; Choi, Sung-Jae; Park, Kyeongsoon; Park, Jong Woong; Kim, Kwangmeyung; Choi, Kuiwon; Yoon, Soo-Young; Youn, Inchan

    2013-06-19

    The activity of rheumatoid arthritis (RA) correlates with the expression of proteases. Among several proteases, matrix metalloproteinase-3 (MMP-3) is one of the biological markers used to diagnose RA. The active form of MMP-3 is a key enzyme involved in RA-associated destruction of cartilage and bone. Thus, detection of active MMP-3 in serum or in vivo is very important for early diagnosis of RA. In this study, a soluble MMP-3 probe was prepared to monitor RA progression by detecting expression of active MMP-3 in collagen-induced arthritis (CIA) mice in vivo in both serum and fibroblast-like synoviocytes (FLSs). The MMP-3 probe exhibited strong sensitivity to MMP-3 and moderate sensitivity to MMP-7 at nanomolecular concentrations, but was not sensitive to other MMPs such as MMP-2, MMP-9, and MMP-13. In an optical imaging study, the MMP-3 probe produced early and strong NIR fluorescence signals prior to observation of erythema and swelling in CIA mice. The MMP-3 probe was able to rapidly and selectively detect and monitor active MMP-3 in diluted serum from CIA mice. Furthermore, histological data demonstrated that activated FLSs in arthritic knee joints expressed active MMP-3. Together, our results demonstrated that the MMP-3 probe may be useful for detecting active MMP-3 for diagnosis of RA. More importantly, the MMP-3 probe was able to detect active MMP-3 in diluted serum with high sensitivity. Therefore, the MMP-3 probe developed in this study may be a very promising probe, useful as a biomarker for early detection and diagnosis of RA.

  9. Towards spark-proof gaseous pixel detectors

    NASA Astrophysics Data System (ADS)

    Tsigaridas, S.; Beuzekom, M. v.; Chan, H. W.; Graaf, H. v. d.; Hartjes, F.; Heijhoff, K.; Hessey, N. P.; Prodanovic, V.

    2016-11-01

    The micro-pattern gaseous pixel detector, is a promising technology for imaging and particle tracking applications. It is a combination of a gas layer acting as detection medium and a CMOS pixelated readout-chip. As a prevention against discharges we deposit a protection layer on the chip and then integrate on top a micromegas-like amplification structure. With this technology we are able to reconstruct 3D track segments of particles passing through the gas thanks to the functionality of the chip. We have turned a Timepix3 chip into a gaseous pixel detector and tested it at the SPS at Cern. The preliminary results are promising and within the expectations. However, the spark protection layer needs further improvement to make reliable detectors. For this reason, we have created a setup for spark-testing. We present the first results obtained from the lab-measurements along with preliminary results from the testbeam.

  10. Pixel lensing observations towards globular clusters

    NASA Astrophysics Data System (ADS)

    Cardone, V. F.; Cantiello, M.

    2003-07-01

    It has been suggested that a monitoring program employing the pixel lensing method to search for microlensing events towards galactic globular clusters may increase the statistics and discriminate among different halo models. Stimulated by this proposal, we evaluate an upper limit to the pixel lensing event rate for such a survey. Four different dark halo models have been considered changing both the flattening and the slope of the mass density profile. The lens mass function has been modelled as a homogenous power - law for mu in (mul, muu) and both the mass limits and the slope of the mass function have been varied to investigate their effect on the rate. The target globular clusters have been selected in order to minimize the disk contribution to the event rate. We find that a pixel lensing survey towards globular clusters is unable to discriminate among different halo models since the number of detectable events is too small to allow any reliable statistical analysis.

  11. Vivid, full-color aluminum plasmonic pixels

    PubMed Central

    Olson, Jana; Manjavacas, Alejandro; Liu, Lifei; Chang, Wei-Shun; Foerster, Benjamin; King, Nicholas S.; Knight, Mark W.; Nordlander, Peter; Halas, Naomi J.; Link, Stephan

    2014-01-01

    Aluminum is abundant, low in cost, compatible with complementary metal-oxide semiconductor manufacturing methods, and capable of supporting tunable plasmon resonance structures that span the entire visible spectrum. However, the use of Al for color displays has been limited by its intrinsically broad spectral features. Here we show that vivid, highly polarized, and broadly tunable color pixels can be produced from periodic patterns of oriented Al nanorods. Whereas the nanorod longitudinal plasmon resonance is largely responsible for pixel color, far-field diffractive coupling is used to narrow the plasmon linewidth, enabling monochromatic coloration and significantly enhancing the far-field scattering intensity of the individual nanorod elements. The bright coloration can be observed with p-polarized white light excitation, consistent with the use of this approach in display devices. The resulting color pixels are constructed with a simple design, are compatible with scalable fabrication methods, and provide contrast ratios exceeding 100:1. PMID:25225385

  12. Modulation transfer function of a trapezoidal pixel array detector

    NASA Astrophysics Data System (ADS)

    Wang, Fan; Guo, Rongli; Ni, Jinping; Dong, Tao

    2016-01-01

    The modulation transfer function (MTF) is the tool most commonly used for quantifying the performance of an electro-optical imaging system. Recently, trapezoid-shaped pixels were designed and used in a retina-like sensor in place of rectangular-shaped pixels. The MTF of a detector with a trapezoidal pixel array is determined according to its definition. Additionally, the MTFs of detectors with differently shaped pixels, but the same pixel areas, are compared. The results show that the MTF values of the trapezoidal pixel array detector are obviously larger than those of rectangular and triangular pixel array detectors at the same frequencies.

  13. Molecular structures and dynamics of the stepwise activation mechanism of a matrix metalloproteinase zymogen: challenging the cysteine switch dogma.

    PubMed

    Rosenblum, Gabriel; Meroueh, Samy; Toth, Marta; Fisher, Jed F; Fridman, Rafael; Mobashery, Shahriar; Sagi, Irit

    2007-11-07

    Activation of matrix metalloproteinase zymogen (pro-MMP) is a vital homeostatic process, yet its molecular basis remains unresolved. Using stopped-flow X-ray spectroscopy of the active site zinc ion, we determined the temporal sequence of pro-MMP-9 activation catalyzed by tissue kallikrein protease in milliseconds to several minutes. The identity of three intermediates seen by X-ray spectroscopy was corroborated by molecular dynamics simulations and quantum mechanics/molecular mechanics calculations. The cysteine-zinc interaction that maintains enzyme latency is disrupted via active-site proton transfers that mediate transient metal-protein coordination events and eventual binding of water. Unexpectedly, these events ensue as a direct result of complexation of pro-MMP-9 and kallikrein and occur before proteolysis and eventual dissociation of the pro-peptide from the catalytic site. Here we demonstrate the synergism among long-range protein conformational transitions, local structural rearrangements, and fine atomic events in the process of zymogen activation.

  14. Hydrogen sulfide mitigates matrix metalloproteinase-9 activity and neurovascular permeability in hyperhomocysteinemic mice.

    PubMed

    Tyagi, Neetu; Givvimani, Srikanth; Qipshidze, Natia; Kundu, Soumi; Kapoor, Shray; Vacek, Jonathan C; Tyagi, Suresh C

    2010-01-01

    An elevated level of homocysteine (Hcy), known as hyperhomocysteinemia (HHcy), was associated with neurovascular diseases. At physiological levels, hydrogen sulfide (H(2)S) protected the neurovascular system. Because Hcy was also a precursor of hydrogen sulfide (H(2)S), we sought to test whether the H(2)S protected the brain during HHcy. Cystathionine-beta-synthase heterozygous (CBS+/-) and wild type (WT) mice were supplemented with or without NaHS (30 microM/L, H(2)S donor) in drinking water. Blood flow and cerebral microvascular permeability in pial vessels were measured by intravital microscopy in WT, WT+NaHS, CBS-/+ and (CBS-/+)+NaHS-treated mice. The brain tissues were analyzed for matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) by Western blot and RT-PCR. The mRNA levels of CBS and cystathionine gamma lyase (CSE, enzyme responsible for conversion of Hcy to H(2)S) genes were measured by RT-PCR. The results showed a significant increase in MMP-2, MMP-9, TIMP-3 protein and mRNA in CBS (-/+) mice, while H(2)S treatment mitigated this increase. Interstitial localization of MMPs was also apparent through immunohistochemistry. A decrease in protein and mRNA expression of TIMP-4 was observed in CBS (-/+) mice. Microscopy data revealed increase in permeability in CBS (-/+) mice. These effects were ameliorated by H(2)S and suggested that physiological levels of H(2)S supplementation may have therapeutic potential against HHcy-induced microvascular permeability, in part, by normalizing the MMP/TIMP ratio in the brain.

  15. Physics performance of the ATLAS pixel detector

    NASA Astrophysics Data System (ADS)

    Tsuno, S.

    2017-01-01

    In preparation for LHC Run-2 the ATLAS detector introduced a new pixel detector, the Insertable B-Layer (IBL). This detector is located between the beampipe and what was the innermost pixel layer. The tracking and vertex reconstruction are significantly improved and good performance is expected in high level objects such a b-quark jet tagging. This in turn, leads to better physics results. This note summarizes the impact of the IBL detector on physics results, especially focusing on the analyses using b-quark jets throughout 2016 summer physics program.

  16. Line profile modelling for multi-pixel CZT detectors

    NASA Astrophysics Data System (ADS)

    Chattopadhyay, T.; Vadawale, S. V.; Rao, A. R.; Bhattacharya, D.; Mithun, N. P. S.; Bhalerao, V.

    2016-07-01

    Cadmium Zinc Telluride (CZT) detectors have been the mainstay for hard X-ray astronomy for its high quantum efficiency, fine energy resolution, near room temperature operation, and radiation hardness. In order to fully utilize the spectroscopic capabilities of CZT detectors, it is important to generate accurate response matrix, which in turn requires precise modelling of the line profiles for the CZT detectors. We have developed a numerical model taking into account the mobility and lifetime of the charge carriers and intrpixel charge sharing for the CZT detectors. This paper describes the details of the modelling along with the experimental measurements of mobility, lifetime and charge sharing fractions for the CZT detector modules of thickness of 5 mm and 2.5 mm pixel size procured from Orbotech Medical Solutions (same modules used in AstroSat-CZTI).

  17. Ag@AgI, core@shell structure in agarose matrix as hybrid: synthesis, characterization, and antimicrobial activity.

    PubMed

    Ghosh, Somnath; Saraswathi, A; Indi, S S; Hoti, S L; Vasan, H N

    2012-06-05

    A novel in situ core@shell structure consisting of nanoparticles of Ag (Ag Nps) and AgI in agarose matrix (Ag@AgI/agarose) has been synthesized as a hybrid, in order to have an efficient antibacterial agent for repetitive usage with no toxicity. The synthesized core@shell structure is very well characterized by XRD, UV-visible, photoluminescence, and TEM. A detailed antibacterial studies including repetitive cycles are carried out on Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) bacteria in saline water, both in dark and on exposure to visible light. The hybrid could be recycled for the antibacterial activity and is nontoxic toward human cervical cancer cells (HeLa cells). The water insoluble Ag@AgI in agarose matrix forms a good coating on quartz, having good mechanical strength. EPR and TEM studies are carried out on the Ag@AgI/agarose and the bacteria, respectively, to elucidate a possible mechanism for killing of the bacteria.

  18. Transcriptional activation by a matrix associating region-binding protein. contextual requirements for the function of bright.

    PubMed

    Kaplan, M H; Zong, R T; Herrscher, R F; Scheuermann, R H; Tucker, P W

    2001-06-15

    Bright (B cell regulator of IgH transcription) is a B cell-specific, matrix associating region-binding protein that transactivates gene expression from the IgH intronic enhancer (E mu). We show here that Bright has multiple contextual requirements to function as a transcriptional activator. Bright cannot transactivate via out of context, concatenated binding sites. Transactivation is maximal on integrated substrates. Two of the three previously identified binding sites in E mu are required for full Bright transactivation. The Bright DNA binding domain defined a new family, which includes SWI1, a component of the SWI.SNF complex shown to have high mobility group-like DNA binding characteristics. Similar to one group of high mobility group box proteins, Bright distorts E mu binding site-containing DNA on binding, supporting the concept that it mediates E mu remodeling. Transfection studies further implicate Bright in facilitating spatially separated promoter-enhancer interactions in both transient and stable assays. Finally, we show that overexpression of Bright leads to enhanced DNase I sensitivity of the endogenous E mu matrix associating regions. These data further suggest that Bright may contribute to increased gene expression by remodeling the immunoglobulin locus during B cell development.

  19. 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

  20. 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

  1. Design, optimization and evaluation of a "smart" pixel sensor array for low-dose digital radiography

    NASA Astrophysics Data System (ADS)

    Wang, Kai; Liu, Xinghui; Ou, Hai; Chen, Jun

    2016-04-01

    Amorphous silicon (a-Si:H) thin-film transistors (TFTs) have been widely used to build flat-panel X-ray detectors for digital radiography (DR). As the demand for low-dose X-ray imaging grows, a detector with high signal-to-noise-ratio (SNR) pixel architecture emerges. "Smart" pixel is intended to use a dual-gate photosensitive TFT for sensing, storage, and switch. It differs from a conventional passive pixel sensor (PPS) and active pixel sensor (APS) in that all these three functions are combined into one device instead of three separate units in a pixel. Thus, it is expected to have high fill factor and high spatial resolution. In addition, it utilizes the amplification effect of the dual-gate photosensitive TFT to form a one-transistor APS that leads to a potentially high SNR. This paper addresses the design, optimization and evaluation of the smart pixel sensor and array for low-dose DR. We will design and optimize the smart pixel from the scintillator to TFT levels and validate it through optical and electrical simulation and experiments of a 4x4 sensor array.

  2. Density matrix renormalization group (DMRG) method as a common tool for large active-space CASSCF/CASPT2 calculations

    NASA Astrophysics Data System (ADS)

    Nakatani, Naoki; Guo, Sheng

    2017-03-01

    This paper describes an interface between the density matrix renormalization group (DMRG) method and the complete active-space self-consistent field (CASSCF) method and its analytical gradient, as well as an extension to the second-order perturbation theory (CASPT2) method. This interfacing allows large active-space multi-reference computations to be easily performed. The interface and its extension are both implemented in terms of reduced density matrices (RDMs) which can be efficiently computed via the DMRG sweep algorithm. We also present benchmark results showing that, in practice, the DMRG-CASSCF calculations scale with active-space size in a polynomial manner in the case of quasi-1D systems. Geometry optimization of a binuclear iron-sulfur cluster using the DMRG-CASSCF analytical gradient is demonstrated, indicating that the inclusion of the valence p-orbitals of sulfur and double-shell d-orbitals of iron lead to non-negligible changes in the geometry compared to the results of small active-space calculations. With the exception of the selection of M values, many computational settings in these practical DMRG calculations have been tuned and black-boxed in our interface, and so the resulting DMRG-CASSCF and DMRG-CASPT2 calculations are now available to novice users as a common tool to compute strongly correlated electronic wavefunctions.

  3. 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.

  4. 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.

  5. AMPK Activation by Metformin Suppresses Abnormal Extracellular Matrix Remodeling in Adipose Tissue and Ameliorates Insulin Resistance in Obesity.

    PubMed

    Luo, Ting; Nocon, Allison; Fry, Jessica; Sherban, Alex; Rui, Xianliang; Jiang, Bingbing; Xu, X Julia; Han, Jingyan; Yan, Yun; Yang, Qin; Li, Qifu; Zang, Mengwei

    2016-08-01

    Fibrosis is emerging as a hallmark of metabolically dysregulated white adipose tissue (WAT) in obesity. Although adipose tissue fibrosis impairs adipocyte plasticity, little is known about how aberrant extracellular matrix (ECM) remodeling of WAT is initiated during the development of obesity. Here we show that treatment with the antidiabetic drug metformin inhibits excessive ECM deposition in WAT of ob/ob mice and mice with diet-induced obesity, as evidenced by decreased collagen deposition surrounding adipocytes and expression of fibrotic genes including the collagen cross-linking regulator LOX Inhibition of interstitial fibrosis by metformin is likely attributable to the activation of AMPK and the suppression of transforming growth factor-β1 (TGF-β1)/Smad3 signaling, leading to enhanced systemic insulin sensitivity. The ability of metformin to repress TGF-β1-induced fibrogenesis is abolished by the dominant negative AMPK in primary cells from the stromal vascular fraction. TGF-β1-induced insulin resistance is suppressed by AMPK agonists and the constitutively active AMPK in 3T3L1 adipocytes. In omental fat depots of obese humans, interstitial fibrosis is also associated with AMPK inactivation, TGF-β1/Smad3 induction, aberrant ECM production, myofibroblast activation, and adipocyte apoptosis. Collectively, integrated AMPK activation and TGF-β1/Smad3 inhibition may provide a potential therapeutic approach to maintain ECM flexibility and combat chronically uncontrolled adipose tissue expansion in obesity.

  6. A strategy to establish a gene-activated matrix on titanium using gene vectors protected in a polylactide coating.

    PubMed

    Kolk, Andreas; Haczek, Cornelia; Koch, Christian; Vogt, Stephan; Kullmer, Martin; Pautke, Christoph; Deppe, Herbert; Plank, Christian

    2011-10-01

    Bioactive implants are promising tools in regenerative medicine. Here we describe a versatile procedure for preparing a gene-activated matrix on titanium. Lyophilized copolymer-protected gene vectors (COPROGs) suspended in poly(d,l-lactide) (PDLLA) solutions in ethyl acetate were used to varnish solid surfaces. The gene-activated PDLLA surfaces were first established on polypropylene 96-well plates. Vector release from these surfaces in aqueous buffer, cell viability and gene transfer efficiency to NIH 3T3 fibroblasts was strongly dependent on the vector dose and its ratio to PDLLA film thickness. A detailed analysis of these relationships allowed establishing correlations which can be used to calculate suitable combinations of COPROGs and PDLLA yielding optimal gene transfer efficiency. This was verified with COPROG-activated PDLLA coatings on titanium foils. HEK 293 and mesenchymal stem cells expressed the BMP-2 gene comprised in the gene-activated surface in a manner that was consistent with the predicted dose-response and toxicity profiles found in NIH 3T3 cells. The systematic procedure presented here for identifying optimal coating compositions can be applied to any combination of vector type and coating material.

  7. Initial steps toward the realization of large area arrays of single photon counting pixels based on polycrystalline silicon TFTs

    NASA Astrophysics Data System (ADS)

    Liang, Albert K.; Koniczek, Martin; Antonuk, Larry E.; El-Mohri, Youcef; Zhao, Qihua; Jiang, Hao; Street, Robert A.; Lu, Jeng Ping

    2014-03-01

    The thin-film semiconductor processing methods that enabled creation of inexpensive liquid crystal displays based on amorphous silicon transistors for cell phones and televisions, as well as desktop, laptop and mobile computers, also facilitated the development of devices that have become ubiquitous in medical x-ray imaging environments. These devices, called active matrix flat-panel imagers (AMFPIs), measure the integrated signal generated by incident X rays and offer detection areas as large as ~43×43 cm2. In recent years, there has been growing interest in medical x-ray imagers that record information from X ray photons on an individual basis. However, such photon counting devices have generally been based on crystalline silicon, a material not inherently suited to the cost-effective manufacture of monolithic devices of a size comparable to that of AMFPIs. Motivated by these considerations, we have developed an initial set of small area prototype arrays using thin-film processing methods and polycrystalline silicon transistors. These prototypes were developed in the spirit of exploring the possibility of creating large area arrays offering single photon counting capabilities and, to our knowledge, are the first photon counting arrays fabricated using thin film techniques. In this paper, the architecture of the prototype pixels is presented and considerations that influenced the design of the pixel circuits, including amplifier noise, TFT performance variations, and minimum feature size, are discussed.

  8. An Antifungal Combination Matrix Identifies a Rich Pool of Adjuvant Molecules that Enhance Drug Activity Against Diverse Fungal Pathogens

    PubMed Central

    Robbins, Nicole; Spitzer, Michaela; Yu, Tennison; Cerone, Robert P.; Averette, Anna K.; Bahn, Yong-Sun; Heitman, Joseph; Sheppard, Donald C.; Tyers, Mike; Wright, Gerard D.

    2015-01-01

    SUMMARY There is an urgent need to identify new treatments for fungal infections. By combining sub-lethal concentrations of the known antifungals fluconazole, caspofungin, amphotericin B, terbinafine, benomyl and cyprodinil with ~3600 compounds in diverse fungal species, we generated a deep reservoir of chemical-chemical interactions termed the Antifungal Combinations Matrix (ACM). Follow-up susceptibility testing against a fluconazole resistant isolate of C. albicans unveiled ACM combinations capable of potentiating fluconazole in this clinical strain. We used chemical genetics to elucidate the mode-of-action of the antimycobacterial drug clofazimine, a compound with unreported antifungal activity that synergized with several antifungals. Clofazimine induces a cell membrane stress for which the Pkc1 signaling pathway is required for tolerance. Further tests against additional fungal pathogens, including Aspergillus fumigatus, highlighted that clofazimine exhibits efficacy as a combination agent against multiple fungi. Thus, the ACM is a rich reservoir of chemical combinations with therapeutic potential against diverse fungal pathogens. PMID:26549450

  9. Inhibitory effect of acetylsalicylic acid on matrix metalloproteinase - 2 activity in human endothelial cells exposed to high glucose.

    PubMed

    Nicolae, Manuela; Tircol, Magdalena; Alexandru, Dorin

    2005-01-01

    Matrix metalloproteinases play a major role in the process of angiogenesis, an important feature of diabetes complications, cancer or rheumatoid arthritis. High glucose concentrations were reported to augment metalloproteinase-2 secretion in some cell types. In the present study we investigated the influence of acetylsalicylic acid on metalloproteinase- 2 secretion and expression in endothelial cells cultured for one week in high glucose conditions (25 mM and 33 mM). Metalloproteinase-2 activity was evidenced by gel zymography, the protein was identified by Western blotting, and the gene expression was quantitated by RT-PCR. The results indicated a marked inhibitory effect of acetylsalicylic acid at gene expression level (approximately 43%) and also at secretion level in samples of conditioned media (approximately 30%) and cellular homogenates (approximately 70%). This may suggest that acetylsalicylic acid could have a beneficial effect in preventing the angiogenic process that appears in diabetes complications.

  10. Separating DDTs in edible animal fats using matrix solid-phase dispersion extraction with activated carbon filter, Toyobo-KF.

    PubMed

    Furusawa, Naoto

    2006-09-01

    A technique is presented for the economical, routine, and quantitative analysis of contamination by dichloro-diphenyl-trichloroethanes (DDTs) [pp'-DDT, pp'-dichlorodiphenyl dichloroethylene, and pp'-dichlorodiphenyl dichloreothane in beef tallow and chicken fat samples, based on their separation using matrix solid-phase dispersion (MSPD) extraction with Toyobo-KF, an activated carbon fiber. Toyobo-KF is a newly applied MSPD sorbent, and it is followed by reversed-phase high-performance liquid chromatography (HPLC) with a photodiode array detector. The resulting analytical performance parameters [recoveries of spiked DDTs (0.1, 0.2, and 0.4 microg/g) > or = 81%, with relative standard deviations of < or = 8% (n = 5), and quantitation limits < or = 0.03 microg/g], with minimal handling and cost-efficiency, indicate that the present MSPD-HPLC method may be a useful tool for routine monitoring of DDT contamination in meat.

  11. 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.

  12. Correlating In Vitro Target-Oriented Screening and Docking: Inhibition of Matrix Metalloproteinases Activities by Flavonoids.

    PubMed

    Crascì, Lucia; Basile, Livia; Panico, Annamaria; Puglia, Carmelo; Bonina, Francesco P; Basile, Pierluigi Maria; Rizza, Luisa; Guccione, Salvatore

    2017-03-13

    Metalloproteases are a family of zinc-containing endopeptidases involved in a variety of pathological disorders. The use of flavonoid derivatives as potential metalloprotease inhibitors has recently increased.Particular plants growing in Sicily are an excellent yielder of the flavonoids luteolin, apigenin, and their respective glycoside derivatives (7-O-rutinoside, 7-O-glucoside, and 7-O-glucuronide).The inhibitory activity of luteolin, apigenin, and their respective glycoside derivatives on the metalloproteases MMP-1, MMP-3, MMP-13, MMP-8, and MMP-9 was assessed and rationalized correlating in vitro target-oriented screening and in silico docking.The flavones apigenin, luteolin, and their respective glucosides have good ability to interact with metalloproteases and can also be lead compounds for further development. Glycones are more active on MMP-1, -3, -8, and -13 than MMP-9. Collagenases MMP-1, MMP-8, and MMP-13 are inhibited by compounds having rutinoside glycones. Apigenin and luteolin are inactive on MMP-1, -3, and -8, which can be interpreted as a better selectivity for both -9 and -13 peptidases. The more active compounds are apigenin-7-O-rutinoside on MMP-1 and luteolin-7-O-rutinoside on MMP-3. The lowest IC50 values were also found for apigenin-7-O-glucuronide, apigenin-7-O-rutinoside, and luteolin-7-O-glucuronide. The glycoside moiety might allow for a better anchoring to the active site of MMP-1, -3, -8, -9, and -13. Overall, the in silico data are substantially in agreement with the in vitro ones (fluorimetric assay).

  13. Fully 3D-Integrated Pixel Detectors for X-Rays

    SciTech Connect

    Deptuch, Grzegorz W.; Gabriella, Carini; Enquist, Paul; Grybos, Pawel; Holm, Scott; Lipton, Ronald; Maj, Piotr; Patti, Robert; Siddons, David Peter; Szczygiel, Robert; Yarema, Raymond

    2016-01-01

    The vertically integrated photon imaging chip (VIPIC1) pixel detector is a stack consisting of a 500-μm-thick silicon sensor, a two-tier 34-μm-thick integrated circuit, and a host printed circuit board (PCB). The integrated circuit tiers were bonded using the direct bonding technology with copper, and each tier features 1-μm-diameter through-silicon vias that were used for connections to the sensor on one side, and to the host PCB on the other side. The 80-μm-pixel-pitch sensor was the direct bonding technology with nickel bonded to the integrated circuit. The stack was mounted on the board using Sn–Pb balls placed on a 320-μm pitch, yielding an entirely wire-bond-less structure. The analog front-end features a pulse response peaking at below 250 ns, and the power consumption per pixel is 25 μW. We successful completed the 3-D integration and have reported here. Additionally, all pixels in the matrix of 64 × 64 pixels were responding on well-bonded devices. Correct operation of the sparsified readout, allowing a single 153-ns bunch timing resolution, was confirmed in the tests on a synchrotron beam of 10-keV X-rays. An equivalent noise charge of 36.2 e- rms and a conversion gain of 69.5 μV/e- with 2.6 e- rms and 2.7 μV/e- rms pixel-to-pixel variations, respectively, were measured.

  14. Fully 3D-Integrated Pixel Detectors for X-Rays

    DOE PAGES

    Deptuch, Grzegorz W.; Gabriella, Carini; Enquist, Paul; ...

    2016-01-01

    The vertically integrated photon imaging chip (VIPIC1) pixel detector is a stack consisting of a 500-μm-thick silicon sensor, a two-tier 34-μm-thick integrated circuit, and a host printed circuit board (PCB). The integrated circuit tiers were bonded using the direct bonding technology with copper, and each tier features 1-μm-diameter through-silicon vias that were used for connections to the sensor on one side, and to the host PCB on the other side. The 80-μm-pixel-pitch sensor was the direct bonding technology with nickel bonded to the integrated circuit. The stack was mounted on the board using Sn–Pb balls placed on a 320-μm pitch,more » yielding an entirely wire-bond-less structure. The analog front-end features a pulse response peaking at below 250 ns, and the power consumption per pixel is 25 μW. We successful completed the 3-D integration and have reported here. Additionally, all pixels in the matrix of 64 × 64 pixels were responding on well-bonded devices. Correct operation of the sparsified readout, allowing a single 153-ns bunch timing resolution, was confirmed in the tests on a synchrotron beam of 10-keV X-rays. An equivalent noise charge of 36.2 e- rms and a conversion gain of 69.5 μV/e- with 2.6 e- rms and 2.7 μV/e- rms pixel-to-pixel variations, respectively, were measured.« less

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

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

    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.

  16. 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

  17. Dynamic holography using pixelated light modulators.

    PubMed

    Zwick, Susanne; Haist, Tobias; Warber, Michael; Osten, Wolfgang

    2010-09-01

    Dynamic holography using spatial light modulators is a very flexible technique that offers various new applications compared to static holography. We give an overview on the technical background of dynamic holography focusing on pixelated spatial light modulators and their technical restrictions, and we present a selection of the numerous applications of dynamic holography.

  18. Synthesis of derivatives of methyl rosmarinate and their inhibitory activities against matrix metalloproteinase-1 (MMP-1).

    PubMed

    Yuan, Hu; Lu, Weiqiang; Wang, Liyan; Shan, Lei; Li, Honglin; Huang, Jin; Sun, Qingyan; Zhang, Weidong

    2013-04-01

    A series of MMP-1 inhibitors have been identified based upon a methyl rosmarinate scaffold using structure-based drug design methods. The best compound in the series showed an IC50 value of 0.4 μM. A docking study was conducted for compound (S)-10n in order to investigate its binding interactions with MMP-1. The structure-activity relationships (SAR) were also briefly discussed. Useful SAR was established which provides important guidelines for the design of future generations of potent inhibitors against MMP-1.

  19. 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.

  20. SIGMAR1 Regulates Membrane Electrical Activity in Response to Extracellular Matrix Stimulation to Drive Cancer Cell Invasiveness.

    PubMed

    Crottès, David; Rapetti-Mauss, Raphael; Alcaraz-Perez, Francisca; Tichet, Mélanie; Gariano, Giuseppina; Martial, Sonia; Guizouarn, Hélène; Pellissier, Bernard; Loubat, Agnès; Popa, Alexandra; Paquet, Agnès; Presta, Marco; Tartare-Deckert, Sophie; Cayuela, Maria Luisa; Martin, Patrick; Borgese, Franck; Soriani, Olivier

    2016-02-01

    The sigma 1 receptor (Sig1R) is a stress-activated chaperone that regulates ion channels and is associated with pathologic conditions, such as stroke, neurodegenerative diseases, and addiction. Aberrant expression levels of ion channels and Sig1R have been detected in tumors and cancer cells, such as myeloid leukemia and colorectal cancer, but the link between ion channel regulation and Sig1R overexpression during malignancy has not been established. In this study, we found that Sig1R dynamically controls the membrane expression of the human voltage-dependent K(+) channel human ether-à-go-go-related gene (hERG) in myeloid leukemia and colorectal cancer cell lines. Sig1R promoted the formation of hERG/β1-integrin signaling complexes upon extracellular matrix stimulation, triggering the activation of the PI3K/AKT pathway. Consequently, the presence of Sig1R in cancer cells increased motility and VEGF secretion. In vivo, Sig1R expression enhanced the aggressiveness of tumor cells by potentiating invasion and angiogenesis, leading to poor survival. Collectively, our findings highlight a novel function for Sig1R in mediating cross-talk between cancer cells and their microenvironment, thus driving oncogenesis by shaping cellular electrical activity in response to extracellular signals. Given the involvement of ion channels in promoting several hallmarks of cancer, our study also offers a potential strategy to therapeutically target ion channel function through Sig1R inhibition.

  1. Minocycline Attenuates Neonatal Germinal-Matrix-Hemorrhage-Induced Neuroinflammation and Brain Edema by Activating Cannabinoid Receptor 2.

    PubMed

    Tang, Jun; Chen, Qianwei; Guo, Jing; Yang, Liming; Tao, Yihao; Li, Lin; Miao, Hongping; Feng, Hua; Chen, Zhi; Zhu, Gang

    2016-04-01

    Germinal matrix hemorrhage (GMH) is the most common neurological disease of premature newborns leading to detrimental neurological sequelae. Minocycline has been reported to play a key role in neurological inflammatory diseases by controlling some mechanisms that involve cannabinoid receptor 2 (CB2R). The current study investigated whether minocycline reduces neuroinflammation and protects the brain from injury in a rat model of collagenase-induced GMH by regulating CB2R activity. To test this hypothesis, the effects of minocycline and a CB2R antagonist (AM630) were evaluated in male rat pups that were post-natal day 7 (P7) after GMH. We found that minocycline can lead to increased CB2R mRNA expression and protein expression in microglia. Minocycline significantly reduced GMH-induced brain edema, microglial activation, and lateral ventricular volume. Additionally, minocycline enhanced cortical thickness after injury. All of these neuroprotective effects of minocycline were prevented by AM630. A cannabinoid CB2 agonist (JWH133) was used to strengthen the hypothesis, which showed the identical neuroprotective effects of minocycline. Our study demonstrates, for the first time, that minocycline attenuates neuroinflammation and brain injury in a rat model of GMH, and activation of CBR2 was partially involved in these processes.

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

    PubMed

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

    2015-11-26

    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.

  3. 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

  4. Fluid shear promotes chondrosarcoma cell invasion by activating matrix metalloproteinase 12 via IGF-2 and VEGF signaling pathways

    PubMed Central

    Wang, P; Chen, S-H; Hung, W-C; Paul, C; Zhu, F; Guan, P-P; Huso, DL; Kontrogianni-Konstantopoulos, A; Konstantopoulos, K

    2015-01-01

    Interstitial fluid flow in and around the tumor tissue is a physiologically relevant mechanical signal that regulates intracellular signaling pathways throughout the tumor. Yet, the effects of interstitial flow and associated fluid shear stress on the tumor cell function have been largely overlooked. Using in vitro bioengineering models in conjunction with molecular cell biology tools, we found that fluid shear (2 dyn/cm2) markedly upregulates matrix metalloproteinase 12 (MMP-12) expression and its activity in human chondrosarcoma cells. MMP-12 expression is induced in human chondrocytes during malignant transformation. However, the signaling pathway regulating MMP-12 expression and its potential role in human chondrosarcoma cell invasion and metastasis have yet to be delineated. We discovered that fluid shear stress induces the synthesis of insulin growth factor-2 (IGF-2) and vascular endothelial growth factor (VEGF) B and D, which in turn transactivate MMP-12 via PI3-K, p38 and JNK signaling pathways. IGF-2-, VEGF-B- or VEGF-D-stimulated chondrosarcoma cells display markedly higher migratory and invasive potentials in vitro, which are blocked by inhibiting MMP-12, PI3-K, p38 or JNK activity. Moreover, recombinant human MMP-12 or MMP-12 overexpression can potentiate chondrosarcoma cell invasion in vitro and the lung colonization in vivo. By reconstructing and delineating the signaling pathway regulating MMP-12 activation, potential therapeutic strategies that interfere with chondrosarcoma cell invasion may be identified. PMID:25435370

  5. 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

  6. Adaptive bad pixel correction algorithm for IRFPA based on PCNN

    NASA Astrophysics Data System (ADS)

    Leng, Hanbing; Zhou, Zuofeng; Cao, Jianzhong; Yi, Bo; Yan, Aqi; Zhang, Jian

    2013-10-01

    Bad pixels and response non-uniformity are the primary obstacles when IRFPA is used in different thermal imaging systems. The bad pixels of IRFPA include fixed bad pixels and random bad pixels. The former is caused by material or manufacture defect and their positions are always fixed, the latter is caused by temperature drift and their positions are always changing. Traditional radiometric calibration-based bad pixel detection and compensation algorithm is only valid to the fixed bad pixels. Scene-based bad pixel correction algorithm is the effective way to eliminate these two kinds of bad pixels. Currently, the most used scene-based bad pixel correction algorithm is based on adaptive median filter (AMF). In this algorithm, bad pixels are regarded as image noise and then be replaced by filtered value. However, missed correction and false correction often happens when AMF is used to handle complex infrared scenes. To solve this problem, a new adaptive bad pixel correction algorithm based on pulse coupled neural networks (PCNN) is proposed. Potential bad pixels are detected by PCNN in the first step, then image sequences are used periodically to confirm the real bad pixels and exclude the false one, finally bad pixels are replaced by the filtered result. With the real infrared images obtained from a camera, the experiment results show the effectiveness of the proposed algorithm.

  7. A 2D 4×4 Channel Readout ASIC for Pixelated CdTe Detectors for Medical Imaging Applications

    PubMed Central

    Macias-Montero, Jose-Gabriel; Sarraj, Maher; Chmeissani, Mokhtar; Martínez, Ricardo; Puigdengoles, Carles

    2015-01-01

    We present a 16-channel readout integrated circuit (ROIC) with nanosecond-resolution time to digital converter (TDC) for pixelated Cadmium Telluride (CdTe) gamma-ray detectors. The 4 × 4 pixel array ROIC is the proof of concept of the 10 × 10 pixel array readout ASIC for positron-emission tomography (PET) scanner, positron-emission mammography (PEM) scanner, and Compton gamma camera. The electronics of each individual pixel integrates an analog front-end with switchable gain, an analog to digital converter (ADC), configuration registers, and a 4-state digital controller. For every detected photon, the pixel electronics provides the energy deposited in the detector with 10-bit resolution, and a fast trigger signal for time stamp. The ASIC contains the 16-pixel matrix electronics, a digital controller, five global voltage references, a TDC, a temperature sensor, and a band-gap based current reference. The ASIC has been fabricated with TSMC 0.25 μm mixed-signal CMOS technology and occupies an area of 5.3 mm × 6.8 mm. The TDC shows a resolution of 95.5 ps, a precision of 600 ps at full width half maximum (FWHM), and a power consumption of 130 μW. In acquisition mode, the total power consumption of every pixel is 200 μW. An equivalent noise charge (ENC) of 160 e−RMS at maximum gain and negative polarity conditions has been measured at room temperature. PMID:26744545

  8. A 2D 4×4 Channel Readout ASIC for Pixelated CdTe Detectors for Medical Imaging Applications.

    PubMed

    Macias-Montero, Jose-Gabriel; Sarraj, Maher; Chmeissani, Mokhtar; Martínez, Ricardo; Puigdengoles, Carles

    2015-10-01

    We present a 16-channel readout integrated circuit (ROIC) with nanosecond-resolution time to digital converter (TDC) for pixelated Cadmium Telluride (CdTe) gamma-ray detectors. The 4 × 4 pixel array ROIC is the proof of concept of the 10 × 10 pixel array readout ASIC for positron-emission tomography (PET) scanner, positron-emission mammography (PEM) scanner, and Compton gamma camera. The electronics of each individual pixel integrates an analog front-end with switchable gain, an analog to digital converter (ADC), configuration registers, and a 4-state digital controller. For every detected photon, the pixel electronics provides the energy deposited in the detector with 10-bit resolution, and a fast trigger signal for time stamp. The ASIC contains the 16-pixel matrix electronics, a digital controller, five global voltage references, a TDC, a temperature sensor, and a band-gap based current reference. The ASIC has been fabricated with TSMC 0.25 μm mixed-signal CMOS technology and occupies an area of 5.3 mm × 6.8 mm. The TDC shows a resolution of 95.5 ps, a precision of 600 ps at full width half maximum (FWHM), and a power consumption of 130 μW. In acquisition mode, the total power consumption of every pixel is 200 μW. An equivalent noise charge (ENC) of 160 e(-)RMS at maximum gain and negative polarity conditions has been measured at room temperature.

  9. HEPS-BPIX, a single photon counting pixel detector with a high frame rate for the HEPS project

    NASA Astrophysics Data System (ADS)

    Wei, Wei; Zhang, Jie; Ning, Zhe; Lu, Yunpeng; Fan, Lei; Li, Huaishen; Jiang, Xiaoshan; Lan, Allan K.; Ouyang, Qun; Wang, Zheng; Zhu, Kejun; Chen, Yuanbo; Liu, Peng

    2016-11-01

    China's next generation light source, named the High Energy Photon Source (HEPS), is currently under construction. HEPS-BPIX (HEPS-Beijing PIXel) is a dedicated pixel readout chip that operates in single photon counting mode for X-ray applications in HEPS. Designed using CMOS 0.13 μm technology, the chip contains a matrix of 104×72 pixels. Each pixel measures 150 μm×150 μm and has a counting depth of 20 bits. A bump-bonded prototyping detector module with a 300-μm thick silicon sensor was tested in the beamline of Beijing Synchrotron Radiation Facility. A fast stream of X-ray images was demonstrated, and a frame rate of 1.2 kHz was proven, with a negligible dead time. The test results showed an equivalent noise charge of 115 e- rms after bump bonding and a threshold dispersion of 55 e- rms after calibration.

  10. Structure activity relationship of antioxidative property of flavonoids and inhibitory effect on matrix metalloproteinase activity in UVA-irradiated human dermal fibroblast.

    PubMed

    Sim, Gwan-Sub; Lee, Bum-Chun; Cho, Ho Seung; Lee, Jae Woong; Kim, Jin-Hwa; Lee, Dong-Hwan; Kim, Jin-Hui; Pyo, Hyeong-Bae; Moon, Dong Cheul; Oh, Ki-Wan; Yun, Yeo Pyo; Hong, Jin Tae

    2007-03-01

    Collagenase, a matrix metalloproteinases (MMPs), is a key regulator in the photoaging process of skin due to the reactive oxygen species generated after exposure to ultraviolet A (UVA). Flavonoid compounds have been demonstrated to possess antioxidant properties, and could be useful in the prevention of photoaging. In this study, to investigate the structure-activity relationship of flavonoid compounds on their antioxidant property and inhibitory effects against the MMP activity, the effects of several flavonoids; myricetin, quercetin, kaempferol, luteolin, apigenin and chrysin, on the reactive oxygen species scavengering activity and inhibitory effect against the MMP activity were examined in vitro and in human dermal fibroblasts induced by UVA. The relative order of antioxidative efficacy, as determined using the 1, 1-diphenyl-2-picrylhydrazyl (DPPH) method and the xanthine/xanthine oxidase system, was as follows; flavones: luteolin > apigenin > chrysin, flavonols: myricetin > quercetin > kaempferol, and correlated with the respective number of OH group on their B-ring. In good correlation with the antioxidant properties, the flavonoids inhibited the collagenase activities, in a dose-dependent manner, and the MMP expression. These results suggested the UVA induced antioxidative activity and inhibitory effects of flavonoids on the collagenase in human dermal fibroblasts depends on the number of OH group in the flavonoid structure, and those with a higher number of OH group may be more useful in the prevention of UV stressed skin aging.

  11. Iron sensitizes keratinocytes and fibroblasts to UVA-mediated matrix metalloproteinase-1 through TNF-α and ERK activation.

    PubMed

    Jian, Jinlong; Pelle, Edward; Yang, Qing; Pernodet, Nadine; Maes, Daniel; Huang, Xi

    2011-03-01

    Oestrogen deficiency is regarded as the main causative factor in postmenopausal skin ageing and photoageing. While women after menopause experience low levels of oestrogen because of cease of ovarian function, they are also exposed to high levels of iron as a result of cessation of menstruation. In this study, we investigated whether this increase in iron presents a risk to the postmenopausal skin. Because of the lack of appropriate animal models to closely mimic the low oestrogen and high iron conditions, we tested the hypothesis in a high iron and low oestrogen culture model. Here, we showed that primary human dermal fibroblasts exposed to iron did not affect the baseline levels of matrix metalloproteinase-1 (MMP-1) activity. However, the iron-exposed fibroblasts were sensitized to UVA exposure, which resulted in a synergistic increase in MMP-1. UVA activated the three members of MAPK family: ERKs, p38, and JNKs. Additional activation of ERKs by iron contributed to the synergistic increases. Primary normal human epidermal keratinocytes (NHEK) did not respond to iron or UVA exposure as measured by MMP-1, but produced tumor necrosis factor-alpha (TNF-α) in the media, which then stimulated MMP-1 in fibroblasts. Our results indicate that iron and UVA increase MMP-1 activity in dermal fibroblasts not only directly through ERK activation but also by an indirect paracrine loop through TNF-α released by NHEK. We conclude that in addition to oestrogen deficiency, increased iron as a result of menopause could be a novel risk factor by sensitizing postmenopausal skin to solar irradiation.

  12. Cleavage of extracellular matrix in periodontitis: gingipains differentially affect cell adhesion activities of fibronectin and tenascin-C

    PubMed Central

    Ruggiero, Sabrina; Cosgarea, Raluca; Potempa, Jan; Potempa, Barbara; Eick, Sigrun; Chiquet, Matthias

    2014-01-01

    Gingipains are cysteine proteases that represent major virulence factors of the periodontopathogenic bacterium Porphyromonas gingivalis. Gingipains are reported to degrade extracellular matrix (ECM) of periodontal tissues, leading to tissue destruction and apoptosis. The exact mechanism is not known, however. Fibronectin and tenascin-C are pericellular ECM glycoproteins present in periodontal tissues. Whereas fibronectin mediates fibroblast adhesion, tenascin-C binds to fibronectin and inhibits its cell-spreading activity. Using purified proteins in vitro, we asked whether fibronectin and tenascin-C are cleaved by gingipains at clinically relevant concentrations, and how fragmentation by the bacterial proteases affects their biological activity in cell adhesion. Fibronectin was cleaved into distinct fragments by all three gingipains; however, only arginine-specific HRgpA and RgpB but not lysine-specific Kgp destroyed its cell-spreading activity. This result was confirmed with recombinant cell-binding domain of fibronectin. Of the two major tenascin-C splice variants, the large but not the small was a substrate for gingipains, indicating that cleavage occurred primarily in the alternatively spliced domain. Surprisingly, cleavage of large tenascin-C variant by all three gingipains generated fragments with increased anti-adhesive activity towards intact fibronectin. Fibronectin and tenascin-C fragments were detected in gingival crevicular fluid of a subset of periodontitis patients. We conclude that cleavage by gingipains directly affects the biological activity of both fibronectin and tenascin-C in a manner that might lead to increased cell detachment and loss during periodontal disease. PMID:23313574

  13. Iron sensitizes keratinocytes and fibroblasts to UVA-mediated matrix metalloproteinase-1 through TNF-α and ERK activation

    PubMed Central

    Jian, Jinlong; Pelle, Edward; Yang, Qing; Pernodet, Nadine; Maes, Daniel; Huang, Xi

    2010-01-01

    Oestrogen deficiency is regarded as the main causative factor in postmenopausal skin ageing and photoageing. While women after menopause experience low levels of oestrogen because of cease of ovarian function, they are also exposed to high levels of iron as a result of cessation of menstruation. In this study, we investigated whether this increase in iron presents a risk to the postmenopausal skin. Because of the lack of appropriate animal models to closely mimic the low oestrogen and high iron conditions, we tested the hypothesis in a high iron and low oestrogen culture model. Here, we showed that primary human dermal fibroblasts exposed to iron did not affect the baseline levels of matrix metalloproteinase-1 (MMP-1) activity. However, the iron-exposed fibroblasts were sensitized to UVA exposure, which resulted in a synergistic increase in MMP-1. UVA activated the three members of MAPK family: ERKs, p38, and JNKs. Additional activation of ERKs by iron contributed to the synergistic increases. Primary normal human epidermal keratinocytes (NHEK) did not respond to iron or UVA exposure as measured by MMP-1, but produced tumor necrosis factor-alpha (TNF-α) in the media, which then stimulated MMP-1 in fibroblasts. Our results indicate that iron and UVA increase MMP-1 activity in dermal fibroblasts not only directly through ERK activation but also by an indirect paracrine loop through TNF-α released by NHEK. We conclude that in addition to oestrogen deficiency, increased iron as a result of menopause could be a novel risk factor by sensitizing postmenopausal skin to solar irradiation. PMID:20701626

  14. Comparative study of various pixel photodiodes for digital radiography: Junction structure, corner shape and noble window opening

    NASA Astrophysics Data System (ADS)

    Kang, Dong-Uk; Cho, Minsik; Lee, Dae Hee; Yoo, Hyunjun; Kim, Myung Soo; Bae, Jun Hyung; Kim, Hyoungtaek; Kim, Jongyul; Kim, Hyunduk; Cho, Gyuseong

    2012-05-01

    Recently, large-size 3-transistors (3-Tr) active pixel complementary metal-oxide silicon (CMOS) image sensors have been being used for medium-size digital X-ray radiography, such as dental computed tomography (CT), mammography and nondestructive testing (NDT) for consumer products. We designed and fabricated 50 µm × 50 µm 3-Tr test pixels having a pixel photodiode with various structures and shapes by using the TSMC 0.25-m standard CMOS process to compare their optical characteristics. The pixel photodiode output was continuously sampled while a test pixel was continuously illuminated by using 550-nm light at a constant intensity. The measurement was repeated 300 times for each test pixel to obtain reliable results on the mean and the variance of the pixel output at each sampling time. The sampling rate was 50 kHz, and the reset period was 200 msec. To estimate the conversion gain, we used the mean-variance method. From the measured results, the n-well/p-substrate photodiode, among 3 photodiode structures available in a standard CMOS process, showed the best performance at a low illumination equivalent to the typical X-ray signal range. The quantum efficiencies of the n+/p-well, n-well/p-substrate, and n+/p-substrate photodiodes were 18.5%, 62.1%, and 51.5%, respectively. From a comparison of pixels with rounded and rectangular corners, we found that a rounded corner structure could reduce the dark current in large-size pixels. A pixel with four rounded corners showed a reduced dark current of about 200fA compared to a pixel with four rectangular corners in our pixel sample size. Photodiodes with round p-implant openings showed about 5% higher dark current, but about 34% higher sensitivities, than the conventional photodiodes.

  15. Design Methodology: ASICs with complex in-pixel processing for Pixel Detectors

    SciTech Connect

    Fahim, Farah

    2014-10-31

    The development of Application Specific Integrated Circuits (ASIC) for pixel detectors with complex in-pixel processing using Computer Aided Design (CAD) tools that are, themselves, mainly developed for the design of conventional digital circuits requires a specialized approach. Mixed signal pixels often require parasitically aware detailed analog front-ends and extremely compact digital back-ends with more than 1000 transistors in small areas below 100μm x 100μm. These pixels are tiled to create large arrays, which have the same clock distribution and data readout speed constraints as in, for example, micro-processors. The methodology uses a modified mixed-mode on-top digital implementation flow to not only harness the tool efficiency for timing and floor-planning but also to maintain designer control over compact parasitically aware layout.

  16. Reactivity and activation of dioxygen-derived species in aprotic media (a model matrix for biomembranes).

    PubMed

    Sawyer, D T; Roberts, J L; Calderwood, T S; Sugimoto, H; McDowell, M S

    1985-12-17

    In aprotic media the electrochemical reduction of dioxygen yields superoxide ion (O2-), which is an effective Brønsted base, nucleophile, one-electron reductant, and one-electron oxidant of reduced transition metal ions. With electrophilic substrates (organic halides and carbonyl carbons) O2- displaces a leaving group to form a peroxy radical (ROO.) in the primary process. Superoxide ion oxidizes the activated hydrogen atoms of ascorbic acid, catechols, hydrophenazines and hydroflavins. Combination of O2- with 1,2-diphenylhydrazine yields the anion radical of azobenzene, which reacts with O2 to give azobenzene and O2- (an example of O2--induced autoxidation). With phenylhydrazine, O2- produces phenyl radicals. The in situ formation of HO2. (O2- plus a proton source) results in H-atom abstraction from allylic and other groups with weak heteroatom--H bonds (binding energy (b.e.) less than 335 kJ). This is a competitive process with the facile second-order disproportionation of HO2. to H2O2 and O2 (kbi approximately equal to 10(4) mol-1 s-1 in Me2SO). Addition of [FeII(MeCN)4] (ClO4)2 to solutions of hydrogen peroxide in dry acetonitrile catalyses a rapid disproportionation of H2O2 via the initial formation of an adduct [FeII(H2O2)2+----Fe(O)(H2O)2+], which oxidizes a second H2O2 to oxygen. In the presence of organic substrates such as 1,4-cyclohexadiene, 1,2-diphenylhydrazine, catechols and thiols the FeII-H2O2/MeCN system yields dehydrogenated products; with alcohols, aldehydes, methylstyrene, thioethers, sulphoxides, and phosphines, the FeII(H2O2)2+ adduct promotes their monoxygenation. The product from the FeO2+-H2O2 reaction, [FeII(H2O2)22+], exhibits chemistry that is closely similar to that for singlet oxygen (1O2), which has been confirmed by the stoichiometric dioxygenation of diphenylisobenzofuran, 9,10-diphenylanthracene, rubrene and electron-rich unsaturated carbon-carbon bonds (Ph2C = CPh2, PhC = CPh and cis-PhCH = CHPh). In dry ligand-free acetonitrile

  17. WFC3/IR Cycle 19 Bad Pixel Table Update

    NASA Astrophysics Data System (ADS)

    Hilbert, B.

    2012-06-01

    Using data from Cycles 17, 18, and 19, we have updated the IR channel bad pixel table for WFC3. The bad pixel table contains flags that mark the position of pixels that are dead, unstable, have a bad zeroth read value, or are affected by "blobs". In all, 28,500 of the science pixels (2.77%) are flagged as bad. Observers are encouraged to dither their observations as a means of lessening the effects of these bad pixels. The new bad pixel table is in the calibration database system (CDBS) as w681807ii_bpx.fits.

  18. Integration of the ATLAS FE-I4 Pixel Chip in the Mini Time Projection Chamber

    NASA Astrophysics Data System (ADS)

    Lopez-Thibodeaux, Mayra; Garcia-Sciveres, Maurice; Kadyk, John; Oliver-Mallory, Kelsey

    2013-04-01

    This project deals with development of readout for a Time Projection Chamber (TPC) prototype. This is a type of detector proposed for direct detection of dark matter (WIMPS) with direction information. The TPC is a gaseous charged particle tracking detector composed of a field cage and a gas avalanche detector. The latter is made of two Gas Electron Multipliers in series, illuminating a pixel readout integrated circuit, which measures the distribution in position and time of the output charge. We are testing the TPC prototype, filled with ArCO2 gas, using a Fe-55 x-ray source and cosmic rays. The present prototype uses an FE-I3 chip for readout. This chip was developed about 10 years ago and is presently in use within the ATLAS pixel detector at the LHC. The aim of this work is to upgrade the TPC prototype to use an FE-I4 chip. The FE-I4 has an active area of 336 mm^2 and 26880 pixels, over nine times the number of pixels in the FE-I3 chip, and an active area about six times as much. The FE-I4 chip represents the state of the art of pixel detector readout, and is presently being used to build an upgrade of the ATLAS pixel detector.

  19. Exploring the limits of identifying sub-pixel thermal features using ASTER TIR data

    USGS Publications Warehouse

    Vaughan, R.G.; Keszthelyi, L.P.; Davies, A.G.; Schneider, D.J.; Jaworowski, C.; Heasler, H.

    2010-01-01

    Understanding the characteristics of volcanic thermal emissions and how they change with time is important for forecasting and monitoring volcanic activity and potential hazards. Satellite instruments view volcanic thermal features across the globe at various temporal and spatial resolutions. Thermal features that may be a precursor to a major eruption, or indicative of important changes in an on-going eruption can be subtle, making them challenging to reliably identify with satellite instruments. The goal of this study was to explore the limits of the types and magnitudes of thermal anomalies that could be detected using satellite thermal infrared (TIR) data. Specifically, the characterization of sub-pixel thermal features with a wide range of temperatures is considered using ASTER multispectral TIR data. First, theoretical calculations were made to define a "thermal mixing detection threshold" for ASTER, which quantifies the limits of ASTER's ability to resolve sub-pixel thermal mixing over a range of hot target temperatures and % pixel areas. Then, ASTER TIR data were used to model sub-pixel thermal features at the Yellowstone National Park geothermal area (hot spring pools with temperatures from 40 to 90 ??C) and at Mount Erebus Volcano, Antarctica (an active lava lake with temperatures from 200 to 800 ??C). Finally, various sources of uncertainty in sub-pixel thermal calculations were quantified for these empirical measurements, including pixel resampling, atmospheric correction, and background temperature and emissivity assumptions.

  20. Exploring the limits of identifying sub-pixel thermal features using ASTER TIR data

    NASA Astrophysics Data System (ADS)

    Vaughan, R. Greg; Keszthelyi, Laszlo P.; Davies, Ashley G.; Schneider, David J.; Jaworowski, Cheryl; Heasler, Henry

    2010-01-01

    Understanding the characteristics of volcanic thermal emissions and how they change with time is important for forecasting and monitoring volcanic activity and potential hazards. Satellite instruments view volcanic thermal features across the globe at various temporal and spatial resolutions. Thermal features that may be a precursor to a major eruption, or indicative of important changes in an on-going eruption can be subtle, making them challenging to reliably identify with satellite instruments. The goal of this study was to explore the limits of the types and magnitudes of thermal anomalies that could be detected using satellite thermal infrared (TIR) data. Specifically, the characterization of sub-pixel thermal features with a wide range of temperatures is considered using ASTER multispectral TIR data. First, theoretical calculations were made to define a "thermal mixing detection threshold" for ASTER, which quantifies the limits of ASTER's ability to resolve sub-pixel thermal mixing over a range of hot target temperatures and % pixel areas. Then, ASTER TIR data were used to model sub-pixel thermal features at the Yellowstone National Park geothermal area (hot spring pools with temperatures from 40 to 90 °C) and at Mount Erebus Volcano, Antarctica (an active lava lake with temperatures from 200 to 800 °C). Finally, various sources of uncertainty in sub-pixel thermal calculations were quantified for these empirical measurements, including pixel resampling, atmospheric correction, and background temperature and emissivity assumptions.

  1. 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.

  2. Applications of snake venom components to modulate integrin activities in cell-matrix interactions

    PubMed Central

    Marcinkiewicz, Cezary

    2013-01-01

    Snake venom proteins are broadly investigated in the different areas of life science. Direct interaction of these compounds with cells may involve a variety of mechanisms that result in diverse cellular responses leading to the activation or blocking of physiological functions of the cell. In this review, the snake venom components interacting with integrins will be characterized in context of their effect on cellular response. Currently, two major families of snake venom proteins are considered as integrin-binding molecules. The most attention has been devoted to the disintegrin family, which binds certain types of integrins through specific motifs recognized as a tri-peptide structurally localized on an integrin-binding loop. Other snake venom integrin-binding proteins belong to the C-type lectin family. Snake venom molecules bind to the cellular integrins resulting in a modulation of cell signaling and in consequence, the regulation of cell proliferation, migration and apoptosis. Therefore, snake venom research on the integrin-binding molecules may have significance in biomedicine and basic cell biology. PMID:23811033

  3. XGA resolution full-video microdisplay using light-emitting polymers on a silicon active matrix circuit

    NASA Astrophysics Data System (ADS)

    Abraham, Howard E.; Antoniadis, Homer; Roitman, Daniel B.; Frischknecht, Kyle; Blalock, Travis N.; Nishimura, Ken; Knotts, Thomas A.; Theil, Jeremy A.; Bright, Chris; Miller, Jeffrey N.; Moon, Ronald L.

    2001-02-01

    Capable self-emissive polymers are being developed for use as emitting materials for a variety of display applications. This paper describes the use of standard CMOS integrated circuit silicon wafer technology along with a spin-cast polyfluorene-base polymer emissive layer, to demonstrate an XGA resolution, full video microdisplay. The silicon chip drive circuitry (Analog Pixel-APIX) is described along with results from our efforts to optimize the reflective anode, the semitransparent cathode process, and emissive cell construction. The 1024 X 768 pixel display achieves 200 Cd/m2 brightness at low power (<50 mW) with fast 1 usec response times. In addition, we summarize future directions to achieve color and the need to incorporate a production- worthy seal layer on microdisplays manufactured on silicon wafers.

  4. Pixel-by-pixel absolute phase retrieval using three phase-shifted fringe patterns without markers

    NASA Astrophysics Data System (ADS)

    Jiang, Chufan; Li, Beiwen; Zhang, Song

    2017-04-01

    This paper presents a method that can recover absolute phase pixel by pixel without embedding markers on three phase-shifted fringe patterns, acquiring additional images, or introducing additional hardware component(s). The proposed three-dimensional (3D) absolute shape measurement technique includes the following major steps: (1) segment the measured object into different regions using rough priori knowledge of surface geometry; (2) artificially create phase maps at different z planes using geometric constraints of structured light system; (3) unwrap the phase pixel by pixel for each region by properly referring to the artificially created phase map; and (4) merge unwrapped phases from all regions into a complete absolute phase map for 3D reconstruction. We demonstrate that conventional three-step phase-shifted fringe patterns can be used to create absolute phase map pixel by pixel even for large depth range objects. We have successfully implemented our proposed computational framework to achieve absolute 3D shape measurement at 40 Hz.

  5. ACS/WFC Pixel Stability - Bringing the Pixels Back to the Science

    NASA Astrophysics Data System (ADS)

    Borncamp, David; Grogin, Norman A.; Bourque, Matthew; Ogaz, Sara

    2016-06-01

    Electrical current that has been trapped within the lattice structure of a Charged Coupled Device (CCD) can be present through multiple exposures, which will have an adverse effect on its science performance. The traditional way to correct for this extra charge is to take an image with the camera shutter closed periodically throughout the lifetime of the instrument. These images, generally referred to as dark images, allow for the characterization of the extra charge that is trapped within the CCD at the time of observation. This extra current can then be subtracted out of science images to correct for the extra charge that was there at this time. Pixels that have a charge above a certain threshold of current are marked as “hot” and flagged in the data quality array. However, these pixels may not be "bad" in the traditional sense that they cannot be reliably dark-subtracted. If these pixels are shown to be stable over an anneal period, the charge can be properly subtracted and the extra noise from this dark current can be taken into account. We present the results of a pixel history study that analyzes every pixel of ACS/WFC individually and allows pixels that were marked as bad to be brought back into the science image.

  6. 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.

  7. Environmental Topology and Water Availability Modulates the Catalytic Activity of β-Galactosidase Entrapped in a Nanosporous Silicate Matrix

    PubMed Central

    Burgos, M. Ines; Velasco, Manuel I.; Acosta, Rodolfo H.; Perillo, María A.

    2016-01-01

    In the present work we studied the catalytic activity of E. coli β-Gal confined in a nanoporous silicate matrix (Eβ-Gal) at different times after the beginning of the sol-gel polymerization process. Enzyme kinetic experiments with two substrates (ONPG and PNPG) that differed in the rate-limiting steps of the reaction mechanism for their β-Gal-catalyzed hydrolysis, measurements of transverse relaxation times (T2) of water protons through 1H-NMR, and scanning electron microscopy analysis of the gel nanostructure, were performed. In conjunction, results provided evidence that water availability is crucial for the modulation observed in the catalytic activity of β-Gal as long as water participate in the rate limiting step of the reaction (only with ONPG). In this case, a biphasic rate vs. substrate concentration was obtained exhibiting one phase with catalytic rate constant (kcA), similar to that observed in solution, and another phase with a higher and aging-dependent catalytic rate constant (kcB). More structured water populations (lower T2) correlates with higher catalytic rate constants (kcB). The T2-kcB negative correlation observed along the aging of gels within the 15-days period assayed reinforces the coupling between water structure and the hydrolysis catalysis inside gels. PMID:27811995

  8. Environmental Topology and Water Availability Modulates the Catalytic Activity of β-Galactosidase Entrapped in a Nanosporous Silicate Matrix.

    PubMed

    Burgos, M Ines; Velasco, Manuel I; Acosta, Rodolfo H; Perillo, María A

    2016-11-04

    In the present work we studied the catalytic activity of E. coli β-Gal confined in a nanoporous silicate matrix (Eβ-Gal) at different times after the beginning of the sol-gel polymerization process. Enzyme kinetic experiments with two substrates (ONPG and PNPG) that differed in the rate-limiting steps of the reaction mechanism for their β-Gal-catalyzed hydrolysis, measurements of transverse relaxation times (T2) of water protons through (1)H-NMR, and scanning electron microscopy analysis of the gel nanostructure, were performed. In conjunction, results provided evidence that water availability is crucial for the modulation observed in the catalytic activity of β-Gal as long as water participate in the rate limiting step of the reaction (only with ONPG). In this case, a biphasic rate vs. substrate concentration was obtained exhibiting one phase with catalytic rate constant (kcA), similar to that observed in solution, and another phase with a higher and aging-dependent catalytic rate constant (kcB). More structured water populations (lower T2) correlates with higher catalytic rate constants (kcB). The T2-kcB negative correlation observed along the aging of gels within the 15-days period assayed reinforces the coupling between water structure and the hydrolysis catalysis inside gels.

  9. Inhibition of Histone Deacetylase Activity in Human Endometrial Stromal Cells Promotes Extracellular Matrix Remodelling and Limits Embryo Invasion

    PubMed Central

    Atkinson, Stuart P.; Quiñonero, Alicia; Martínez, Sebastián; Pellicer, Antonio; Simón, Carlos

    2012-01-01

    Invasion of the trophoblast into the maternal decidua is regulated by both the trophoectoderm and the endometrial stroma, and entails the action of tissue remodeling enzymes. Trophoblast invasion requires the action of metalloproteinases (MMPs) to degrade extracellular matrix (ECM) proteins and in turn, decidual cells express tissue inhibitors of MMPs (TIMPs). The balance between these promoting and restraining factors is a key event for the successful outcome of pregnancy. Gene expression is post-transcriptionally regulated by histone deacetylases (HDACs) that unpacks condensed chromatin activating gene expression. In this study we analyze the effect of histone acetylation on the expression of tissue remodeling enzymes and activity of human endometrial stromal cells (hESCs) related to trophoblast invasion control. Treatment of hESCs with the HDAC inhibitor trichostatin A (TSA) increased the expression of TIMP-1 and TIMP-3 while decreased MMP-2, MMP-9 and uPA and have an inhibitory effect on trophoblast invasion. Moreover, histone acetylation is detected at the promoters of TIMP-1 and TIMP-3 genes in TSA-treated. In addition, in an in vitro decidualized hESCs model, the increase of TIMP-1 and TIMP-3 expression is associated with histone acetylation at the promoters of these genes. Our results demonstrate that histone acetylation disrupt the balance of ECM modulators provoking a restrain of trophoblast invasion. These findings are important as an epigenetic mechanism that can be used to control trophoblast invasion. PMID:22291969

  10. Extracellular Vesicle-functionalized Decalcified Bone Matrix Scaffolds with Enhanced Pro-angiogenic and Pro-bone Regeneration Activities

    PubMed Central

    Xie, Hui; Wang, Zhenxing; Zhang, Liming; Lei, Qian; Zhao, Aiqi; Wang, Hongxiang; Li, Qiubai; Cao, Yilin; Jie Zhang, Wen; Chen, Zhichao

    2017-01-01

    Vascularization is crucial for bone regeneration after the transplantation of tissue-engineered bone grafts in the clinical setting. Growing evidence suggests that mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are potently pro-angiogenic both in vitro and in vivo. In the current study, we fabricated a novel EV-functionalized scaffold with enhanced pro-angiogenic and pro-bone regeneration activities by coating decalcified bone matrix (DBM) with MSC-derived EVs. EVs were harvested from rat bone marrow-derived MSCs and the pro-angiogenic potential of EVs was investigated in vitro. DBM scaffolds were then coated with EVs, and the modification was verified by scanning electron microscopy and confocal microscopy. Next, the pro-angiogenic and pro-bone regeneration activities of EV-modified scaffolds were evaluated in a subcutaneous bone formation model in nude mice. Micro-computed tomography scanning analysis showed that EV-modified scaffolds with seeded cells enhanced bone formation. Enhanced bone formation was confirmed by histological analysis. Immunohistochemical staining for CD31 proved that EV-modified scaffolds promoted vascularization in the grafts, thereby enhancing bone regeneration. This novel scaffold modification method provides a promising way to promote vascularization, which is essential for bone tissue engineering. PMID:28367979

  11. Inhibition of matrix metalloproteinase activities and tightening of tight junctions by diallyl disulfide in AGS human gastric carcinoma cells.

    PubMed

    Park, Hyun Soo; Kim, Gi-Young; Choi, Il-Whan; Kim, Nam Deuk; Hwang, Hye Jin; Choi, Young-Whan; Choi, Yung Hyun

    2011-05-01

    The effect of diallyl disulfide (DADS), a major component of an oil-soluble allyl sulfide garlic (Allium sativum) derivative, on the correlation between anti-invasive activity and tightening of tight junctions (TJs) was investigated in human gastric adenocarcinoma AGS cells. Our data indicated that the inhibitory effects of DADS on cell motility and invasiveness were found to be associated with increased tightness of the TJs, which was demonstrated by an increase in transepithelial electrical resistance. Activities of matrix metalloprotease (MMP)-2 and -9 in AGS cells were dose-dependently inhibited by treatment with DADS, and this was also correlated with a decrease in expression of their mRNA and proteins; however, tissue inhibitor of metalloproteinase (TIMP)-1 and -2 mRNA levels and proteins were increased. Additionally, immunoblotting results indicated that DADS repressed the levels of claudin proteins (claudin-2, -3, and -4), major components of TJs that play key roles in control and selectivity of paracellular transport. Although further studies are needed, these results suggest that DADS treatment may inhibit tumor cell motility and invasion and, therefore, act as a dietary source to decrease the risk of cancer metastasis.

  12. Mechanical Strain Induced Expression of Matrix Metalloproteinase-9 via Stretch-Activated Channels in Rat Abdominal Aortic Dissection

    PubMed Central

    Qiu, ZhiHuang; Chen, LiangWan; Cao, Hua; Chen, Qiang; Peng, Hua

    2017-01-01

    Background The aim of the study was to investigate the expression of matrix metalloproteinase-9 (MMP-9) in rat abdominal aortic dissection (AD) induced by mechanical strain, so as to offer a better understanding of the possible mechanisms of AD. Material/Methods Experimental AD in rats was achieved by the injection of porcine pancreatic elastase. At days 0, 1, 3, 5, 7, 14, 21, and 30 after the establishment of AD model, serum MMP-9 levels were measured by enzyme-linked immunosorbent assay (ELISA). Four groups of vascular rings were stretched in vitro with a mechanical strength of 0 g, 1 g, 3 g, or 5 g for 30 min. Another four groups were pretreated with GdCl3, streptomycin, SN50, and SN50M, followed by stretching with 3 g for 30 min. The messenger RNA and the protein of MMP-9 were analyzed by real-time RT-PCR and Western blotting, and NF-κB p65 was detected by ELISA. Results After the establishment of rat abdominal AD model, the serum MMP-9 levels of AD groups increased significantly. The results showed increased expression of MMP-9 in rat AD vessels stretched with mechanical strength of 1 g, 3 g, and 5 g, but this effect was mostly blocked by Gd Cl3 and streptomycin. The NF-κB activity in aortic rings was activated by stretching with a mechanical strength of 3 g and was blocked by SN50, but not by SN50M. Conclusions The expression of MMP-9 in serum was increased significantly after rat abdominal AD formation. Mechanical strain induced MMP-9 expression in AD vessels, which was mediated through the activation of the stretch-activated channel-induced NF-κB pathway. PMID:28286334

  13. Discoidin Domain Receptor 2 Mediates Collagen-Induced Activation of Membrane-Type 1 Matrix Metalloproteinase in Human Fibroblasts.

    PubMed

    Majkowska, Iwona; Shitomi, Yasuyuki; Ito, Noriko; Gray, Nathanael S; Itoh, Yoshifumi

    2017-03-07

    Membrane-Type 1 Matrix Metalloproteinase (MT1-MMP) is a membrane-bound MMP that is highly expressed in cells with invading capacity including fibroblasts and invasive cancer cell. A potential physiological stimulus for MT1-MMP expression is fibrillar collagen, and it has been shown that it upregulates both MT1-MMP gene and