54 results on '"L. Evensen"'
Search Results
2. Hui Malama o ke Kai
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Nani P. Akeo, Irene K. Takeshita, Carl K. Takeshita, Eric S. Bunyan, Shannon M. Hirose-Wong, Carl G. Vasconcellos, David R. Eckart, Sharon S. Majit-Gorion, Shirley L. Evensen, and Kaui N. Burgess
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Coping (psychology) ,Epidemiology ,business.industry ,media_common.quotation_subject ,Public Health, Environmental and Occupational Health ,Ethnic group ,Human factors and ergonomics ,Poison control ,Passion ,Criminology ,Suicide prevention ,Indigenous ,Injury prevention ,Medicine ,business ,media_common - Abstract
The goal of the Hui Malama o ke Kai project was the development of a community-based youth program that supported the prevention of youth violence and substance use among 5th- and 6th-grade students from a predominantly Hawaiian community. This program's development included engaging with a variety of community partners and mobilizing parents through the youths' cultural development. Recommendations for working with Hawaiians and other indigenous peoples include having program evaluators work more intimately with program participants and developing program components that address ethnic identity and family engagement. In doing so, youth programs with indigenous peoples can also galvanize small communities that are coping with destructive social concerns.
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- 2008
- Full Text
- View/download PDF
3. Recent detector developments at SINTEF (industrial presentation)
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L. Evensen, Sjur Mo, B. S. Avset, T. Westgaard, Kari Schjølberg-Henriksen, and Geir Uri Jensen
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Physics ,Nuclear and High Energy Physics ,Silicon ,Physics::Instrumentation and Detectors ,business.industry ,Detector ,chemistry.chemical_element ,Avalanche photodiode ,Physics::Fluid Dynamics ,Condensed Matter::Soft Condensed Matter ,chemistry ,Optoelectronics ,High Energy Physics::Experiment ,business ,Instrumentation ,Radiation hardening - Abstract
Results from SINTEF's research on radiation hardness of silicon detectors, thin silicon detectors, silicon drift devices, reach-through avalanche photodiodes, and detectors with thin dead layers are presented.
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- 1998
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4. Thin detectors for the CHICSi /spl Delta/E-E telescope
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J Mårtensson, Magne Guttormsen, Agneta Oskarsson, T. Westgaard, Lars Carlén, L. Evensen, E.J. van Veldhuizen, Y Murin, Harry J. Whitlow, Bo Jakobsson, A. Siwek, Vladimir Avdeichikov, and Lars Westerberg
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Nuclear and High Energy Physics ,Materials science ,Silicon ,business.industry ,Detector ,chemistry.chemical_element ,law.invention ,Isotope separation ,Telescope ,Optics ,Nuclear Energy and Engineering ,chemistry ,law ,Electronic engineering ,Breakdown voltage ,Wafer ,Electrical and Electronic Engineering ,business ,Leakage (electronics) ,Diode - Abstract
A pilot series of 10 /spl mu/m to 15 /spl mu/m thin silicon detectors has been made for the /spl Delta/E-E telescopes in the CHICSi detector system. This system will operate at the CELSIUS heavy ion storage ring in Uppsala, Sweden. /spl Delta/E-E telescopes provide isotope identification and energy determination of fragments from nuclear collisions. The thin detectors are made as p-i-n diodes in thin etched membranes in 280 /spl mu/m thick silicon wafers. The membranes are made with anisotropic etching using 25 wt.% tetramethylammonium hydroxide (TMAH) solution. The etch speed of this solution is very uniform across a wafer. As a result detectors with uniform thickness can be produced. The etch depth varies with less than /spl plusmn/0.3 /spl mu/m over a wafer and the surface microroughness is in the range from 2 to 4 nm. Each detector has a 10.0 mm/spl times/10.0 mm active area on a 10.2 mm/spl times/10.2 mm membrane surrounded by a 1.1 mm wide supporting frame. The detectors have leakage currents in the active area of approximately 0.5 nA at 20 V. The breakdown voltage of the detectors is above 100 V. Evaluation experiments with telescopes consisting of a thin detector in combination with a thick detector have shown excellent isotope separation capabilities. Mass separation of /sup 6/Li and /sup 7/Li is clearly observable.
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- 1997
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5. Single-sided microstrip detector for high radiation doses
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L. Evensen and T. Westgaard
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Physics ,Nuclear and High Energy Physics ,Silicon ,Physics::Instrumentation and Detectors ,business.industry ,Detector ,chemistry.chemical_element ,STRIPS ,law.invention ,chemistry.chemical_compound ,Capacitor ,chemistry ,Silicon nitride ,law ,Optoelectronics ,High Energy Physics::Experiment ,Resistor ,Silicon oxide ,business ,Instrumentation ,Voltage - Abstract
A “single-sided” microstrip detector with n-type strip implants in n-type silicon substrate materials has been developed for use in high luminosity vertex tracker experiments. This technology has been chosen to make a detector which will operate satisfactorily well beyond the radiation dose which converts the substrate to p-type material. This full-size detector of dimensions 60 mm × 60 mm has 1025 strips (with 512 read-out strips) biased with polysilicon resistors. Separate “p-stop” implants between the strips isolate the strips from each other electrically. These individual p-stops are implemented in order to reduce the detector noise. A combination of silicon oxide and silicon nitride gives a very reliable dielectric layer for the coupling capacitors, which yields a low fraction of defective read-out strips. The backside p-n-junction area is surrounded by a high-stability guard which makes it possible to operate the detector at bias voltages corresponding to several times the depletion voltage. Preliminary irradiation tests carried out in order to determine the detector design's suitability for the experiments at the CERN-Large Hadron Collider have shown that the detectors are not fatally damaged after a radiation dose of 2 × 1014 protons cm−2.
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- 1997
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6. The effect of metal field plates on multiguard structures with floating p+ guard rings
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B.S. Avset and L. Evensen
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Physics ,Nuclear and High Energy Physics ,Guard (information security) ,Physics::Instrumentation and Detectors ,business.industry ,Doping ,Detector ,Oxide ,Metal ,chemistry.chemical_compound ,chemistry ,visual_art ,Guard ring ,visual_art.visual_art_medium ,Optoelectronics ,business ,Instrumentation ,Diode ,Gamma irradiation - Abstract
The performance and stability of silicon diode detectors can be improved by implementing guard ring structures around the active detector area. The purpose of this work is to study design parameters influencing the performance of multiguard structures, especially the effect of metal field plates. An important feature is the potential distribution in the multiguard ring structure which depends on the bulk doping concentration, the oxide charge, the size of the gap between guard rings and the field-plate design. We have made a systematic investigation of the effect of distance between floating p+ guard rings with two different metal field plate designs. We have also varied the width of the field plates and studied the effect of gamma irradiation. Numerical simulations have been done to compare with results from the experimental potential distributions between guard rings.
- Published
- 1996
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7. Radiation hardness of punch-through and FET biased silicon microstrip detectors
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B.S. Avset, T. Westgaard, L. Evensen, and Niaz N. Ahmed
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Physics ,Nuclear and High Energy Physics ,business.industry ,Detector ,Biasing ,Radiation ,Noise (electronics) ,law.invention ,law ,Optoelectronics ,Field-effect transistor ,Irradiation ,Resistor ,business ,Instrumentation ,Radiation hardening - Abstract
Silicon microstrip detectors can be biased with polysilicon resistors or Field Effect Transistor (FET) biasing structures. Polysilicon resistors are radiation hard, but using the FET biasing principle reduces processing costs and can give better noise performance. A set of microstrip detectors has been manufactured with a standard radiation sensor process in order to assess the radiation hardness of punch-through and FET biasing. Eight different bias geometry designs were used in order to study the effects of bias gap lengths and strip end geometries on the detector characteristics. The test detectors were irradiated at several dose levels up to 75 kGy with a 60Co source. Initially the devices had very low oxide charge (3 × 1010 cm−2) and leakage current levels (60 pA per strip). The dynamic resistance was in the 1 GΩ range, which is higher than the values which can be achieved by conventional polysilicon resistors. Radiation exposure gave significant increases in the leakage current of the devices. This causes large reductions in the dynamic resistance, and detector performance will degrade. The degradation due to increased leakage current was present for all strip end geometries, and it could not be compensated by changing the gate voltage.
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- 1996
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8. Industrial Microelectronics towards the Year 2000
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J. Gakkestad, Anders Hanneborg, H. von der Lippe, L. Evensen, A. Kjensmo, B. Sundby Avset, Oddvar Søråsen, P. Ohlckers, M. Nese, F. Serck‐Hanssen, T.-E. Hansen, H. Kristiansen, A. Bjorneklett, E. Nygård, and E. Kristiansen
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Engineering ,business.industry ,Total cost ,Process (engineering) ,Scale (chemistry) ,Integrated circuit ,Condensed Matter Physics ,Atomic and Molecular Physics, and Optics ,Manufacturing engineering ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,law.invention ,law ,Microelectronics ,Applied research ,Instrumentation (computer programming) ,Electronics ,Electrical and Electronic Engineering ,business ,Telecommunications - Abstract
The Center for Industrial Research (SI), the University of Oslo (UiO) and a group of Norwegian companies have collaborated between 1990 and 1992 in the research programme ‘Industrial Microelectronics’ with a total cost of 30 MNOK. The programme was sponsored by the Norwegian Scientific and Industrial Research Council (NTNF) as one of the twin programmes constituting a national research initiative in microelectronics. The motivation for the programme is the recognition of microelectronics as a key technology commanding the performance and market success of many of the electronics systems from the Norwegian electronics industry towards the year 2000. The main objective is to stimulate industrial innovation by developing, transferring and exploiting knowledge and methods based upon advanced microelectronics. Focused activities are silicon sensor technology, combined analogue/digital design of application‐specific integrated circuits, large scale instrumentation, sensor packaging and thermal management of electronic systems. SI is focusing on applied research, UiO on education, and collaborating Norwegian companies are using the results in their own R&D projects. It is anticipated that the research results will be fully industrialised within 3–5 years. The programme is co‐ordinated with other Norwegian government‐sponsored research activities as well as European research programmes based on microelectronics. The programme is organised in projects and monitored with a set of milestones strongly indicating the achievement of successful industrial innovation, research results of international standing and high‐quality education of key personnel for the industry. Several successful examples of the research results are highlighted: Design and process methodology for double‐sided microstrip silicon radiation sensors for detection of high energy elementary particles, silicon‐to‐silicon and silicon‐to‐thin film anodic bonding processes for sensor fabrication, combined analogue/digital application‐specific integrated circuits for front‐end instrumentation applications, packaging of radiation sensors and thermal management of electronic systems by evaporation cooling. It is concluded that the programme has successfully achieved results in harmony with the objective.
- Published
- 1993
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9. A fast low noise silicon detector for electron spectroscopy up to 1 MeV
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Thomas Happ, R. R. Betts, A. H. Wuosmaa, Anders Hanneborg, and L. Evensen
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Physics ,Nuclear and High Energy Physics ,Silicon ,Physics::Instrumentation and Detectors ,Preamplifier ,business.industry ,Detector ,Gamma ray ,chemistry.chemical_element ,Electron ,Scintillator ,Capacitance ,Nuclear magnetic resonance ,chemistry ,Optoelectronics ,business ,Instrumentation ,Diode - Abstract
A 1 mm thick silicon pad detector has been developed for the Atlas Positron Experiment (APEX) [1,2]. This experiment requires efficient detection of positrons and electrons with energies up to 1 MeV with an energy resolution of better than 10 keV and time resolution of less than 2 ns. To satisfy these requirements, the detectors should be 1 mm thick with low leakage current and be capable of operation at voltages greater than needed for full depletion. To enhance the charge collection time, the detectors should also withstand cooling to liquid nitrogen temperature. These requirements have been satisfied using diodes manufactured on high resistivity silicon in combination with a segmented guard ring structure (multiguard) and a process optimized to reduce the bulk generated leakage current. A room temperature leakage current of 1 nA/cm2 was achieved and an energy resolution of 3.6 keV FWHM was measured with 30 pF input capacitance on a charge sensitive preamplifier. At −130°C with 90 pF input capacitance an energy resolution of 3.4 keV FWHM and a time resolution of 1.2 ns was measured for 500 keV electrons in coincidence with gamma rays detected in a BaF2 scintillator detector. Results from the evaluation of different designs and process approaches are discussed.
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- 1993
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10. Temperature dependence of the behaviour of silicon drift detectors
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B.S. Avset, S. Roe, Geoffrey Hall, L. Evensen, G. K. Rochester, and T.J. Summer
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Physics ,Nuclear and High Energy Physics ,Electron mobility ,Photon ,Silicon ,Physics::Instrumentation and Detectors ,business.industry ,Detector ,chemistry.chemical_element ,Cathode ,Anode ,Photodiode ,law.invention ,Optics ,chemistry ,law ,business ,Instrumentation ,Leakage (electronics) - Abstract
Measurements have been carried out on the temperature dependence of the behaviour of two types of drift device: photodiodes and position sensitive drift chambers with segmented anode and cathode structures. Leakage currents and electron mobility have been investigated at low temperature for the drift photodiodes. Self-triggering has been achieved for the position sensitive drift chambers using 60 keV photons, and differences in arrival time between the prompt trigger signal from the cathode and the delayed anode signal have been studied as a function of drift distance and temperature.
- Published
- 1991
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11. Practical limitations to the performance of silicon drift chambers imposed by material quality
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Geoffrey Hall, S. Roe, R. Wheadon, B.S. Avset, and L. Evensen
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Physics ,Nuclear and High Energy Physics ,Silicon ,Physics::Instrumentation and Detectors ,business.industry ,chemistry.chemical_element ,STRIPS ,law.invention ,Anode ,Optics ,chemistry ,law ,Position (vector) ,Material quality ,Resistor ,business ,Instrumentation ,Pulse height - Abstract
Silicon drift chambers with subdivided anode structures intended for two-dimensional position measurement have been produced. These devices use implanted resistor chains to form the drift and have orthogonal strips on the reverse side intended for self-triggering capability. An important consequence of the design is that low drift fields must be used (≤ about 70 V/cm). We present results based on detailed position-response studies which show significant distortions of both pulse height and drift time characteristics. The causes of the distortions will be considered.
- Published
- 1991
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12. Measurement of spatial resolution of a double-sided AC-coupled microstrip detector
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R. A. Brenner, Renato Turchetta, D. Husson, A. Lounis, J. Lindgren, L. Hubbeling, Tuure Tuuva, Iiro Hietanen, B.S. Avset, J. Chauveau, L. Evensen, M. Turala, P. Weilhammer, W. Dulinski, and M. Schaeffer
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Capacitive coupling ,Physics ,Nuclear and High Energy Physics ,Physics::Instrumentation and Detectors ,010308 nuclear & particles physics ,business.industry ,Detector ,Vertical plane ,STRIPS ,01 natural sciences ,Particle detector ,law.invention ,Semiconductor detector ,Optics ,law ,0103 physical sciences ,010306 general physics ,business ,Instrumentation ,Image resolution ,Beam (structure) - Abstract
Capacitively coupled Si strip detectors with readout on both the p-side and the n-side have been developed. A novel scheme to separate strips ohmically on the n-side by means of field depletion via a suitable potential applied to the readout strips has been successfully demonstrated. Results on the spatial resolution of these detectors for both sides measured in a high energy beam are presented. The spatial resolution of the n-side has been measured at different incident angles of the beam tracks with respect to a vertical plane through the n + strips at 0°, 20° and 40°.
- Published
- 1991
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13. Silicon drift photodiodes
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T.-E. Hansen, L. Evensen, Geoffrey Hall, S. Roe, J. Ellison, B.S. Avset, and R. Wheadon
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Physics ,Nuclear and High Energy Physics ,Silicon ,Physics::Instrumentation and Detectors ,business.industry ,Detector ,chemistry.chemical_element ,Electron ,Capacitance ,Photodiode ,law.invention ,Anode ,chemistry ,law ,Ionization ,Optoelectronics ,business ,Instrumentation ,Leakage (electronics) - Abstract
Low capacitance photodiodes based on the principle of the solid state drift chamber have been constructred and tested. The devices are based on a cellular design with an anode at the centre of each of five cells allowing electrons liberated by ionisation to drift up to 1 mm to the readout strip. Results on the performance of the detectors, including leakage current, capacitance and drift properties, are presented and compared with simulations. A second series drift photodiodes have been processed which incorporate improvements based on results acquired from the first design. They have leakage currents of a few nA and shorter drift times at the periphery of the drift cells. We present measurements showing the performance of the new devices.
- Published
- 1990
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14. Hui Malama o ke Kai: mobilizing to prevent youth violence and substance use with passion, common goals, and culture
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Nani P, Akeo, Eric S, Bunyan, Kaui N, Burgess, David R, Eckart, Shirley L, Evensen, Shannon M, Hirose-Wong, Sharon S, Majit-Gorion, Carl K, Takeshita, Irene K, Takeshita, and Carl G, Vasconcellos
- Subjects
Leadership ,Substance-Related Disorders ,Culture ,Organizational Case Studies ,Juvenile Delinquency ,Humans ,Organizational Objectives ,Health Promotion ,Program Development ,Violence ,Child ,Community Networks ,Hawaii - Abstract
The goal of the Hui Malama o ke Kai project was the development of a community-based youth program that supported the prevention of youth violence and substance use among 5th- and 6th-grade students from a predominantly Hawaiian community. This program's development included engaging with a variety of community partners and mobilizing parents through the youths' cultural development. Recommendations for working with Hawaiians and other indigenous peoples include having program evaluators work more intimately with program participants and developing program components that address ethnic identity and family engagement. In doing so, youth programs with indigenous peoples can also galvanize small communities that are coping with destructive social concerns.
- Published
- 2007
15. Characterization of silicon detectors with thin dead-layers on the n-side
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B. S. Avset, P. Weilhammer, E. Chesi, T. Westgaard, S. Mo, Geir Uri Jensen, L. Evensen, Jacques Séguinot, and Paolo Martinengo
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Range (particle radiation) ,Materials science ,Silicon ,business.industry ,Detector ,chemistry.chemical_element ,Alpha particle ,Electron ,Radiation ,equipment and supplies ,chemistry ,Optoelectronics ,Irradiation ,business ,Penetration depth - Abstract
Low energy electrons, alpha particles and X-rays has a short penetration depth in silicon. For detection of these types of radiation it is important that the detector has a shallow inactive region at the side which is irradiated. A series of shallow dead layer test detectors produced by n-side implantation of phosphorus, arsenic or antimony has been characterized. Leakage current levels in the range 2-5 nA/cm/sup 2/ were achieved with dead layers in the range 0.1-0.2 /spl mu/m. A silicon pixel detector which will be used in a hybrid photon detector has been produced with thin dead layer technology. The lower detection limit for electrons with this detector is 2.5 keV.
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- 2002
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16. Radiation damage studies of field plate and p-stop n-side silicon microstrip detectors
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Phillip Allport, Paolo Giubellino, Marek Idzik, R. Wheadon, H. G. Moser, Pawel Grybos, P. Weilhammer, Shaun Roe, Wladyslaw Dabrowski, Luciano Ramello, D. Vité, J.D. Richardson, B.S. Avset, L. Evensen, B. C. MacEvoy, K. Gill, Andrzej Skoczeń, S. Moszczynski, R. J. Apsimon, C. Green, Geoffrey Hall, and J. Matheson
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Physics ,Nuclear and High Energy Physics ,Range (particle radiation) ,Photon ,Field (physics) ,business.industry ,Neutron temperature ,Microstrip ,Optics ,Radiation damage ,Irradiation ,Detectors and Experimental Techniques ,business ,Instrumentation ,Silicon microstrip detectors - Abstract
We present results from studies of the properties of dedicated n-side microstrip structures before and after irradiation, with photons to 7 Mrad and fast neutrons to 8 × 10 13 ncm −2 . Both p-stop and field plate devices were investigated, each having a range of strip geometries in order to determine optimal configurations for long-term viability and performance.
- Published
- 1994
17. Radiation tolerance of single-sided silicon microstrips
- Author
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T. Mouthuy, J. Straver, A. Giraldo, Geoffrey Hall, H. G. Moser, I. Siotis, P A. Delpierre, M. Schuster, S. Moszczynski, Wladyslaw Dabrowski, A. Paccagnella, D. Vité, R. J. Apsimon, P. Weilhammer, N. A. Smith, L. Evensen, Phillip Allport, Stephen Watts, Marek Idzik, R. Wheadon, Paolo Giubellino, A. Hanneborg, M. Robbins, P.S.L. Booth, Demetrios Loukas, J.D. Richardson, Luciano Ramello, Konstantinos Misiakos, A. Holmes-Siedle, M. Schaeffer, J. Michele, Renato Turchetta, K. Zachariadou, Shaun Roe, M. Turala, K. Gill, E. Spiriti, M.-C. Habrard, R. Sachdeva, C. Arrighi, Ivan Mikulec, B.S. Avset, S. Sotthibandhu, J. C. Clemens, T.A. Hansen, Leonid Kurchaninov, Richard Brenner, Peter Chochula, Pawel Grybos, Manfred Krammer, Dario Bisello, W. L. Prado Da Silva, W. Dulinski, Institut de Recherches Subatomiques (IReS), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Cancéropôle du Grand Est-Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Centre de Physique des Particules de Marseille (CPPM), Aix Marseille Université (AMU)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), RD20, and Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Aix Marseille Université (AMU)
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Physics ,Nuclear and High Energy Physics ,Silicon ,Physics::Instrumentation and Detectors ,010308 nuclear & particles physics ,business.industry ,Physics::Medical Physics ,Detector ,chemistry.chemical_element ,01 natural sciences ,Particle detector ,Semiconductor detector ,chemistry ,Neutron flux ,0103 physical sciences ,Radiation damage ,Optoelectronics ,Neutron ,Irradiation ,[PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det] ,Detectors and Experimental Techniques ,010306 general physics ,business ,Instrumentation - Abstract
The RD20 collaboration is investigating the design and operation of an LHC inner tracking detector based on silicon microstrips. Measurements have been made on prototype detectors after irradiation with electrons, neutrons, photons, and protons for doses up to 5 Mrad and fluences up to 10 15 particles/cm 2 . The annealing of effective doping changes caused by high neutron fluences, one of the major limits to detector lifetime at the LHC, is shown to be strongly inhibited by cooling below room temperature. Detailed results are presented on the critical issue of microstrip capacitance. We have also investigated bulk damage caused by high-energy protons, interstrip isolation after neutron irradiation, and MOS capacitors irradiated with electrons and photons.
- Published
- 1994
18. A new microstrip detector with double-sided readout
- Author
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Itzhak Roditi, A. Peisert, V. Chabaud, Renato Turchetta, L. Evensen, Pawel Jalocha, I. Hietanen, P. Bambade, M. Schaeffer, Hans Dijkstra, Tuure Tuuva, A. Czermak, Roland Horisberger, W. Dulinski, B.S. Avset, L. Hubbeling, G. Maehlum, P. Weilhammer, M. Battaglia, M. Turala, Laboratoire de l'Accélérateur Linéaire (LAL), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), and Starita, Sabine
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Nuclear and High Energy Physics ,Materials science ,STRIPS ,01 natural sciences ,Particle detector ,030218 nuclear medicine & medical imaging ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,law ,0103 physical sciences ,[PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det] ,Electrical and Electronic Engineering ,Detectors and Experimental Techniques ,Ohmic contact ,Diode ,Capacitive coupling ,010308 nuclear & particles physics ,business.industry ,Semiconductor device ,Semiconductor detector ,Nuclear Energy and Engineering ,[PHYS.PHYS.PHYS-INS-DET] Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det] ,Optoelectronics ,Resistor ,business - Abstract
A silicon microstrip detector has been developed with 50- mu m-pitch strips on both the p- and n-side, using the principle of capacitive coupling between p/sup +/ diode strips (respectively, n/sup +/ strips) and the metallization strips which connect to the front-end preamplifiers. The detector is biased on both sides via polysilicon resistors connecting each p/sup +/ or n/sup +/ line to a common bias bus. To allow ohmic separation at the n-side, the accumulation layer of electrons has to be disrupted between the n/sup +/ strips. This has been achieved in three different ways: by separate polysilicon lines on thick oxide between two adjacent n/sup +/ lines to break the conducting accumulation layer by externally induced field depletion or by using the metal lines of the n/sup +/ strips on thick oxide or on thin oxide. Results on 20*20-mm/sup 2/ test devices are presented. A preliminary analysis of the spatial resolution gives sigma =16 mu m on both sides. These results demonstrate that double-sided readout Si strip detectors can be used for experiments where spatial resolution in the 10 mu m range is needed. >
- Published
- 1990
19. Bakhtinian Perspectives on Language and Culture : Meaning in Language, Art and New Media
- Author
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F. Bostad, C. Brandist, L. Evensen, H. Faber, F. Bostad, C. Brandist, L. Evensen, and H. Faber
- Subjects
- Language and languages--Philosophy, Culture, Art--Philosophy, Meaning (Philosophy)
- Abstract
In this multi-disciplinary volume, comprising the work of several established scholars from different countries, central concepts associated with the work of the Bakhtin Circle are interrogated in relation to intellectual history, language theory and an understanding of new media. The book will prove an important resource for those interested in the ideas of the Bakhtin Circle, but also for those attempting to develop a coherent theoretical approach to language in use and problems of meaning production in new media.
- Published
- 2004
20. BRACKISH WATER AND FRESHWATER SPECIES OF THE DIATOM GENUSSKELETONEMA.II.SKELETONEMA POTAMOSCOMB. NOV.1
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Grethe Rytter Hasle and Dale L. Evensen
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geography ,geography.geographical_feature_category ,Brackish water ,Frustule ,Plant Science ,Skeletonema potamos ,Aquatic Science ,Biology ,biology.organism_classification ,Salinity ,Diatom ,Botany ,Tributary ,Taxonomy (biology) ,Bay - Abstract
SUMMARY Electron microscope investigations of the siliceous frustule show that the diatom described by Hustedt as Stephanodiscus subsalsus (A. Cleve) Hust. is not Skeletonema subsalsum (A. Cleve) Bethge (Melosira subsalsa A. Cleve) but is Microsiphona potamos Weber. This species is so similar to Skeletonema costatum (Grev.) Cleve and Skeletonema subsalsum that the combination Skeletonema potamos (Weber) Hasle is suggested. Present records classify Skeletonema potamos as a freshwater species of lakes and rivers. In Sandusky Bay, Lake Erie (U.S.A.) and in River Wumme, a tributary of the River Weser (Germany) it grows with Skeletonema subsalsum. In nature, and when grown in cultures at a salinity of 0%, the processes are extremely short; when grown at salinities of 2% or more, the processes are much longer.
- Published
- 1976
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21. BRACKISH WATER AND FRESHWATER SPECIES OF THE DIATOM GENUS SKELETONEMA. II. SKELETONEMA POTAMOS COMB. NOV.1
- Author
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Grethe R. Hasle and Dale L. Evensen
- Subjects
Plant Science ,Aquatic Science - Published
- 1976
- Full Text
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22. A silicon drift photodiode
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L. Evensen, T.-E. Hansen, R. Wheadon, Shaun Roe, J. Ellison, B.S. Avset, and Geoffrey Hall
- Subjects
Physics ,Nuclear and High Energy Physics ,business.industry ,Semiconductor device ,Capacitance ,Particle detector ,Photodiode ,law.invention ,Anode ,Nuclear Energy and Engineering ,law ,Electrical resistivity and conductivity ,Ionization ,Optoelectronics ,Electrical and Electronic Engineering ,Electric current ,business - Abstract
A low-capacitance photodiode based on the principle of the solid-state drift chamber has been constructed and tested. The device is based on a cellular design with an anode at the center of each of five cells, allowing electrons liberated by ionization to drift up to 1 mm to the readout strip. Two designs were produced with p/sup +/ implant widths of 75 mu m and 85 mu m, respectively, using n-type material of 3.5-k Omega -cm resistivity. The opposite surface is a uniform p-type implant, features matching those of the other surface, and is unmetallized to ensure good photosensitivity. Results on the performance of the detector, including leakage current, capacitance, and drift properties, are presented and compared with simulation results. >
- Published
- 1989
- Full Text
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23. An effect of osmotic pressure on the valve morphology of the diatom Skeletonema subsalsum (A. Cleve) Bethge
- Author
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S. Johansson, E. Paasche, and D. L. Evensen
- Subjects
Growth medium ,biology ,fungi ,Skeletonema subsalsum ,Plant Science ,Aquatic Science ,Plankton ,biology.organism_classification ,Salinity ,chemistry.chemical_compound ,Diatom ,chemistry ,Botany ,Osmotic pressure ,Growth rate ,Valve morphology - Abstract
The valve morphology of the brackish-water plankton diatom Skeletonema subsalsum is dependent on salinity. In cells grown at salinities of 3‰ or less, the valve faces were flat and the connecting processes much reduced in length. Cells grown at salinities of 5‰ or higher had dome-shaped valves and extended connecting processes. The effect of an increase in salinity could be duplicated by the addition of sucrose to the growth medium. The growth rate was nearly independent of salinity in the range of 1–10‰. It was concluded that the osmotic pressure of the medium exerts a direct effect on cell-wall morphogenesis in S. subsalsum.
- Published
- 1975
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24. Brackish-water and fresh-water species of the diatom genus Skeletonema Grev. I. Skeletonema subsalsum (A. Cleve) Bethge
- Author
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Grethe Rytter Hasle and Dale L. Evensen
- Subjects
Diatom ,Circular hole ,Fresh water ,Brackish water ,Genus ,Botany ,Type locality ,Skeletonema subsalsum ,Plant Science ,Aquatic Science ,Biology ,biology.organism_classification - Abstract
Type material of Skeletonema subsalsum has been examined by light and electron microscopy. The species belongs to Skeletonema and is not conspecific with Stephanodiscus subsalsus. Skeletonema subsalsum is distinguished from S. costatum morphologically mainly by structure of connecting processes, those of S. subsalsum being tubular with a basal circular hole while those of S. costatum are trough-shaped with a wide basal opening. In addition to the Stockholm Archipelago (type locality), S. subsalsum was recorded from the Gulf of Finland and the river Wumme in the Bremen area.
- Published
- 1975
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- View/download PDF
25. Recent development of detectors with integrated capacitors and polysilicon resistors
- Author
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H. Kaukouen, A. Zalewska, L. Hubbeling, P. Weilhammer, A. Piesert, L. Evensen, T.E. Hansen, G. Maehlum, Tuure Tuuva, and Roland Horisberger
- Subjects
Capacitive coupling ,Nuclear and High Energy Physics ,Materials science ,business.industry ,Polysilicon depletion effect ,Capacitance ,law.invention ,Capacitor ,Nuclear Energy and Engineering ,law ,Optoelectronics ,Breakdown voltage ,Electrical and Electronic Engineering ,Resistor ,business ,Decoupling (electronics) ,Diode - Abstract
A silicon microstrip detector has been developed with capacitive coupling of the diode strips to the metallization and with polysilicon bias resistors to each diode. It allows the decoupling of the leakage current from the input to the charge-sensitive amplifier. Results are given on the coupling capacity and the breakdown voltage as well as on the polysilicon line resistance. It is found that the coupling capacitance, varying between 25 pF and 80 pF as a function of the oxide thickness, is large enough to avoid capacitance signal losses to the backplane. The 200-nm-thick silicon oxide withstands a potential difference of 100 V or more, thus allowing the operation of the detector with the metal strips and backplane at a ground potential and the bias voltage applied to the diodes. >
- Published
- 1988
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26. Punch-through currents and floating strip potentials in silicon detectors
- Author
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Geoffrey Hall, J. Ellison, L. Evensen, S. Roe, B.S. Avset, and R. Wheadon
- Subjects
Physics ,Nuclear and High Energy Physics ,Silicon ,Physics::Instrumentation and Detectors ,business.industry ,Detector ,chemistry.chemical_element ,ComputerApplications_COMPUTERSINOTHERSYSTEMS ,STRIPS ,Particle detector ,Semiconductor detector ,law.invention ,Nuclear Energy and Engineering ,chemistry ,law ,Optoelectronics ,Electrical and Electronic Engineering ,Atomic physics ,Current (fluid) ,business ,Current density ,Voltage - Abstract
Punch-through currents flowing between adjacent p/sup +/ strips on the surface of silicon microstrip drift detectors have been observed. Measurements of the floating strip potential have shown that a p/sup +/ strip acquires a voltage such that the punch-through current and the leakage current are equal and opposite. The factors influencing the threshold for the punch-through effect have been compared with a simple computer model, and the predicted variation with the interstrip gap is found to be in reasonable agreement with measured values for a variety of detectors. >
- Published
- 1989
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27. Pharmacokinetics and metabolism of diphenoxylate in man
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A. Karim, K. L. Evensen, M. L. Clark, and R. E. Ranney
- Subjects
Adult ,Male ,Chromatography, Gas ,Hydrochloride ,Urine ,Pharmacology ,Models, Biological ,Excretion ,Feces ,chemistry.chemical_compound ,Gastrointestinal Agents ,Pharmacokinetics ,Isonipecotic Acids ,Nitriles ,medicine ,Humans ,Pharmacology (medical) ,Biotransformation ,Diphenoxylate ,Carbon Isotopes ,Cyanides ,Feces analysis ,Half-life ,Metabolism ,Kinetics ,chemistry ,Chromatography, Thin Layer ,Half-Life ,medicine.drug - Abstract
The absorption, excretion, and biotransformation of 14C-diphenoxylate hydrochloride (5 mg. containing 20.2 µc of 14C) when administered orally in ethanolic solution and without the presence of atropine sulfate was studied in 3 men. The mean urinary and fecal excretion of the total label in a 96 hour period was 13.65 ± 1.18 per cent and 49.20 ± 2.24 per cent, respectively. Thin-layer radiochromatographic analysis of the label in excreta indicated extensive biotransformation of the parent drug. In the urine, the maior metabolites were characterized as diphenoxylic acid and hydroxydiphenoxylic acid. These acids were present in both the free and coniugated fractions. Radioactivity in the plasma was associated largely with diphenoxylic acid and to a smaller extent with the unchanged drug. Pharmacokinetic analysis using a one-compartment open model showed a rapid absorption (t½ = 19.7 ± 1.7 minutes; peak level at 2.0 hours) of diphenoxylate followed by its rapid elimination (t½ = 2.50 ± 0.34 hours). The plasma half-life (t½ = 4.38 ± 1.04 hours) of diphenoxylic acid was higher than that of diphenoxylate.
- Published
- 1972
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28. Development Of Silicon Drift Chambers For X-Ray Astronomy
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C. C. Zammit, Geoffrey Hall, G. K. Rochester, S. Roe, B. S. Avset, L. Evensen, R. Wheadon, and T. J. Sumner
- Subjects
Physics ,X-ray astronomy ,Silicon ,Physics::Instrumentation and Detectors ,business.industry ,Detector ,chemistry.chemical_element ,X-ray telescope ,Gamma-ray astronomy ,Photodiode ,law.invention ,Optics ,chemistry ,law ,Extreme ultraviolet ,business ,Diode - Abstract
Detectors for x-ray (1-10 keV) astronomy based on silicon drift chamber (SDC) devices offer significant advantages over some types of existing detector and the potential performance of such devices is summarised. Our development program is outlined together with a discussion of device designs which are being pursued. Results are presented from some recently acquired two-dimensional drift devices working at room temperature, and from some large area drift diodes working at low temperature.
- Published
- 1989
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29. A Si strip detector with integrated coupling capacitors
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Tuure Tuuva, A. Zalewska, L. Evensen, Roland Horisberger, A. Peisert, Massimo Caccia, P. Weilhammer, T.E. Hansen, and L. Hubbeling
- Subjects
Capacitive coupling ,Physics ,Nuclear and High Energy Physics ,Physics::Instrumentation and Detectors ,Preamplifier ,business.industry ,Detector ,STRIPS ,Computer Science::Other ,law.invention ,Capacitor ,law ,Optoelectronics ,Resistor ,Detectors and Experimental Techniques ,business ,Instrumentation ,Decoupling (electronics) ,Diode - Abstract
A silicon microstrip detector with capacitive coupling of the diode strips to the metallization and with individual polysilicon resistors to each diode has been developed. The detector was tested in a minimum ionizing particle beam showing a performance similar to conventional strip detectors and a spatial resolution of 3.5 μm. Capacitive coupling allows the decoupling of the leakage current from the input to the charge sensitive preamplifier especially in the case of LSI electronics.
- Published
- 1987
30. Clinical experience with a new preparation of Rh 0 (D) immune globulin (human)
- Author
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J F, Wurzel, L M, Hansen, and K L, Evensen
- Subjects
Adult ,Erythroblastosis, Fetal ,Rh-Hr Blood-Group System ,Pregnancy ,Blood Group Incompatibility ,Immune Sera ,Humans ,Female ,ABO Blood-Group System - Published
- 1973
31. Human plasma and urine quinine levels following tablets, capsules, and intravenous infusion
- Author
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Eugene C. Madonia, Anthony P. Hall, Kenneth L. Evensen, and Anthony W. Czerwinski
- Subjects
Adult ,Male ,Time Factors ,Capsules ,Urine ,Pharmacology ,medicine ,Leukocytes ,Humans ,Pharmacology (medical) ,Enteric coated ,Adverse effect ,Quinine ,business.industry ,medicine.disease ,Pyrimethamine ,Human plasma ,Injections, Intravenous ,Tablets, Enteric-Coated ,Headaches ,medicine.symptom ,business ,Malaria ,medicine.drug - Published
- 1973
32. Thin detectors for the CHICSi ΔE-E telescope
- Author
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T. Westgaard, Bo Jakobsson, L. Evensen, and Harry J. Whitlow
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Telescope ,Materials science ,Optics ,law ,business.industry ,Detector ,business ,law.invention
33. Radiation hardness of Si strip detectors with integrated coupling capacitors
- Author
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P. Weilhammer, A. Peisert, Tuure Tuuva, G. Maehlum, L. Evensen, Roland Horisberger, L. Hubbeling, and Hans Dijkstra
- Subjects
Physics ,Nuclear and High Energy Physics ,Physics::Instrumentation and Detectors ,business.industry ,Detector ,Particle detector ,Computer Science::Other ,Semiconductor detector ,law.invention ,Capacitor ,Nuclear Energy and Engineering ,law ,Optoelectronics ,High Energy Physics::Experiment ,Irradiation ,Electrical and Electronic Engineering ,Resistor ,business ,Radiation hardening ,Diode - Abstract
Si strip detectors with integrated coupling capacitors between diode and metallization and with separate bias resistors for each strip have been exposed to ionising radiation. Results from measurements of detector response before and after irradiation are presented. >
- Published
- 1989
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34. Antiviral Immunoglobulins of Chicken Egg Yolk for Potential Prevention of SARS-CoV-2 Infection.
- Author
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Ravlo E, Evensen L, Sanson G, Hildonen S, Ianevski A, Skjervold PO, Ji P, Wang W, Kaarbø M, Kaynova GD, Kainov DE, and Bjørås M
- Subjects
- Animals, Spike Glycoprotein, Coronavirus genetics, Chickens, SARS-CoV-2, Egg Yolk, RNA, Viral, Antibodies, Viral, Antibodies, Neutralizing, Antibodies, Monoclonal, Antiviral Agents, Cytokines, COVID-19 prevention & control
- Abstract
Background: Some viruses cause outbreaks, which require immediate attention. Neutralizing antibodies could be developed for viral outbreak management. However, the development of monoclonal antibodies is often long, laborious, and unprofitable. Here, we report the development of chicken polyclonal neutralizing antibodies against SARS-CoV-2 infection. Methods: Layers were immunized twice with 14-day intervals using the purified receptor-binding domain (RBD) of the S protein of SARS-CoV-2/Wuhan or SARS-CoV-2/Omicron. Eggs were harvested 14 days after the second immunization. Polyclonal IgY antibodies were extracted. Binding of anti-RBD IgYs was analyzed by immunoblot and indirect ELISA. Furthermore, the neutralization capacity of anti-RBD IgYs was measured in Vero-E6 cells infected with SARS-CoV-2-mCherry/Wuhan and SARS-CoV-2/Omicron using fluorescence and/or cell viability assays. In addition, the effect of IgYs on the expression of SARS-CoV-2 and host cytokine genes in the lungs of Syrian Golden hamsters was examined using qRT-PCR. Results: Anti-RBD IgYs efficiently bound viral RBDs in situ, neutralized the virus variants in vitro, and lowered viral RNA amplification, with minimal alteration of virus-mediated immune gene expression in vivo. Conclusions: Altogether, our results indicate that chicken polyclonal IgYs can be attractive targets for further pre-clinical and clinical development for the rapid management of outbreaks of emerging and re-emerging viruses.
- Published
- 2022
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- View/download PDF
35. Identifying Lysophosphatidic Acid Acyltransferase β (LPAAT-β) as the Target of a Nanomolar Angiogenesis Inhibitor from a Phenotypic Screen Using the Polypharmacology Browser PPB2.
- Author
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Poirier M, Awale M, Roelli MA, Giuffredi GT, Ruddigkeit L, Evensen L, Stooss A, Calarco S, Lorens JB, Charles RP, and Reymond JL
- Subjects
- Acyltransferases genetics, Acyltransferases isolation & purification, Biological Assay methods, Cell Culture Techniques, Cell Line, Cell Proliferation drug effects, Drug Evaluation, Preclinical methods, Enzyme Inhibitors metabolism, Human Umbilical Vein Endothelial Cells, Humans, Inhibitory Concentration 50, Models, Molecular, Molecular Structure, Phenotype, Protein Binding, Small Molecule Libraries metabolism, Software, Structure-Activity Relationship, Triazines metabolism, Acyltransferases antagonists & inhibitors, Angiogenesis Inducing Agents metabolism, Enzyme Inhibitors chemistry, Small Molecule Libraries chemistry, Triazines chemistry
- Abstract
By screening a focused library of kinase inhibitor analogues in a phenotypic co-culture assay for angiogenesis inhibition, we identified an aminotriazine that acts as a cytostatic nanomolar inhibitor. However, this aminotriazine was found to be completely inactive in a whole-kinome profiling assay. To decipher its mechanism of action, we used the online target prediction tool PPB2 (http://ppb2.gdb.tools), which suggested lysophosphatidic acid acyltransferase β (LPAAT-β) as a possible target for this aminotriazine as well as several analogues identified by structure-activity relationship profiling. LPAAT-β inhibition (IC
50 ≈15 nm) was confirmed in a biochemical assay and by its effects on cell proliferation in comparison with a known LPAAT-β inhibitor. These experiments illustrate the value of target-prediction tools to guide target identification for phenotypic screening hits and significantly expand the rather limited pharmacology of LPAAT-β inhibitors., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)- Published
- 2019
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- View/download PDF
36. Optical micromanipulation of nanoparticles and cells inside living zebrafish.
- Author
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Johansen PL, Fenaroli F, Evensen L, Griffiths G, and Koster G
- Subjects
- Animals, Animals, Genetically Modified, Erythrocytes metabolism, Macrophages metabolism, Microinjections, Nanotubes chemistry, Micromanipulation methods, Nanoparticles chemistry, Optical Tweezers, Zebrafish metabolism
- Abstract
Regulation of biological processes is often based on physical interactions between cells and their microenvironment. To unravel how and where interactions occur, micromanipulation methods can be used that offer high-precision control over the duration, position and magnitude of interactions. However, lacking an in vivo system, micromanipulation has generally been done with cells in vitro, which may not reflect the complex in vivo situation inside multicellular organisms. Here using optical tweezers we demonstrate micromanipulation throughout the transparent zebrafish embryo. We show that different cells, as well as injected nanoparticles and bacteria can be trapped and that adhesion properties and membrane deformation of endothelium and macrophages can be analysed. This non-invasive micromanipulation inside a whole-organism gives direct insights into cell interactions that are not accessible using existing approaches. Potential applications include screening of nanoparticle-cell interactions for cancer therapy or tissue invasion studies in cancer and infection biology.
- Published
- 2016
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- View/download PDF
37. Zebrafish as a model system for characterization of nanoparticles against cancer.
- Author
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Evensen L, Johansen PL, Koster G, Zhu K, Herfindal L, Speth M, Fenaroli F, Hildahl J, Bagherifam S, Tulotta C, Prasmickaite L, Mælandsmo GM, Snaar-Jagalska E, and Griffiths G
- Subjects
- Animals, Cell Line, Tumor, Disease Models, Animal, Flow Cytometry, Fluorescent Dyes chemistry, HEK293 Cells, Humans, Liposomes chemistry, Macrophages metabolism, Metal Nanoparticles chemistry, Microscopy, Microscopy, Electron, Scanning, Microscopy, Electron, Transmission, Nanomedicine methods, Neoplasms metabolism, Neoplasms therapy, Optical Tweezers, Polyethylene Glycols chemistry, Polymers chemistry, Polystyrenes chemistry, Tissue Distribution, Micromanipulation methods, Nanoparticles chemistry, Neoplasms drug therapy, Zebrafish embryology
- Abstract
Therapeutic nanoparticles (NPs) have great potential to deliver drugs against human diseases. Encapsulation of drugs in NPs protects them from being metabolized, while they are delivered specifically to a target site, thereby reducing toxicity and other side-effects. However, non-specific tissue accumulation of NPs, for example in macrophages, especially in the spleen and liver is a general problem with many NPs being developed for cancer therapy. To address the problem of non-specific tissue accumulation of NPs we describe the development of the zebrafish embryo as a transparent vertebrate system for characterization of NPs against cancer. We show that injection of human cancer cells results in tumor-like structures, and that subsequently injected fluorescent NPs, either made of polystyrene or liposomes can be imaged in real-time. NP biodistribution and general in vivo properties can be easily monitored in embryos having selective fluorescent labeling of specific tissues. We demonstrate in vitro, by using optical tweezer micromanipulation, microscopy and flow cytometry that polyethylene glycol (PEG) coating of NPs decreases the level of adhesion of NPs to macrophages, and also to cancer cells. In vivo in zebrafish embryos, PEG coating resulted in longer NP circulation times, decreased macrophage uptake, and reduced adhesion to the endothelium. Importantly, liposomes were observed to accumulate passively and selectively in tumor-like structures comprised of human cancer cells. These results show that zebrafish embryo is a powerful system for microscopy-based screening of NPs on the route to preclinical testing.
- Published
- 2016
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- View/download PDF
38. In Vitro Characterization of Valproic Acid, ATRA, and Cytarabine Used for Disease-Stabilization in Human Acute Myeloid Leukemia: Antiproliferative Effects of Drugs on Endothelial and Osteoblastic Cells and Altered Release of Angioregulatory Mediators by Endothelial Cells.
- Author
-
Kvestad H, Evensen L, Lorens JB, Bruserud O, and Hatfield KJ
- Abstract
The combined use of the histone deacetylase inhibitor valproic acid (VPA), the retinoic acid receptor- α agonist all-trans retinoic acid (ATRA), and the deoxyribonucleic acid polymerase- α inhibitor cytarabine (Ara-C) is now considered for disease-stabilizing treatment of acute myeloid leukemia (AML). Leukemogenesis and leukemia cell chemoresistance seem to be supported by neighbouring stromal cells in the bone marrow, and we have therefore investigated the effects of these drugs on primary human endothelial cells and the osteoblastic Cal72 cell line. The results show that VPA and Ara-C have antiproliferative effects, and the antiproliferative/cytotoxic effect of Ara-C was seen at low concentrations corresponding to serum levels found during low-dose in vivo treatment. Furthermore, in functional assays of endothelial migration and tube formation VPA elicited an antiangiogenic effect, whereas ATRA elicited a proangiogenic effect. Finally, VPA and ATRA altered the endothelial cell release of angiogenic mediators; ATRA increased levels of CXCL8, PDGF-AA, and VEGF-D, while VPA decreased VEGF-D and PDGF-AA/BB levels and both drugs reduced MMP-2 levels. Several of these mediators can enhance AML cell proliferation and/or are involved in AML-induced bone marrow angiogenesis, and direct pharmacological effects on stromal cells may thus indirectly contribute to the overall antileukemic activity of this triple drug combination.
- Published
- 2014
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- View/download PDF
39. Contextual compound screening for improved therapeutic discovery.
- Author
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Evensen L, Odlo K, Micklem DR, Littlewood-Evans A, Wood J, Kuzniewski C, Altmann KH, Hansen TV, and Lorens JB
- Subjects
- Angiogenesis Inhibitors chemistry, Animals, Cell Line, Coculture Techniques methods, Human Umbilical Vein Endothelial Cells, Humans, Pulmonary Artery cytology, Structure-Activity Relationship, Zebrafish, Angiogenesis Inhibitors pharmacology, Drug Evaluation, Preclinical methods
- Abstract
Cellular behaviors are governed by combinations of systemic and microenvironmental factors; together, these regulate cell signaling responses to growth factors. This contextual microenvironmental influence also determines drug sensitivity. Hence using in vitro systems that model contextual cellular behavior is highly beneficial for effective therapeutic development. Angiogenesis (formation of blood vessels) is driven by a series of dynamic endothelial cell signaling responses to growth factors under the influence of the vascular extracellular matrix and adjacent pericytes. In vitro primary human vascular cell co-cultures self-assemble into capillary-like structures through reciprocal heterotypic interactions that mimic angiogenic context dynamics. By using temporal live-cell imaging-based analysis, unique angiogenic microenvironments can be delineated to quantify the contextual activity of compound inhibitors. We used this in vitro organotypic contextual screening approach to conduct structure-activity relationship analysis on a combretastatin A-4 analogue series to identify novel compounds with potent vascular disrupting activity in vivo., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2013
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- View/download PDF
40. Tumor versus stromal cells in culture--survival of the fittest?
- Author
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Talasila KM, Brekka N, Mangseth K, Stieber D, Evensen L, Rosland GV, Torsvik A, Wagner M, Niclou SP, Mahesparan R, Vintermyr OK, Bjerkvig R, Nigro JM, and Miletic H
- Subjects
- Animals, Brain Neoplasms metabolism, Glioblastoma metabolism, Humans, In Vitro Techniques, Mutation, Oligodendroglioma metabolism, Rats, Transplantation, Heterologous, Tumor Cells, Cultured, ErbB Receptors metabolism, Stromal Cells pathology
- Abstract
Two of the signature genetic events that occur in human gliomas, EGFR amplification and IDH mutation, are poorly represented in experimental models in vitro. EGFR amplification, for example, occurs in 40 to 50% of GBM, and yet, EGFR amplification is rarely preserved in cell cultures derived from human tumors. To analyze the fate of EGFR amplified and IDH mutated cells in culture, we followed the development over time of cultures derived from human xenografts in nude rats enriched for tumor cells with EGFR amplification and of cultures derived from patient samples with IDH mutations, in serum monolayer and spheroid suspension culture, under serum and serum free conditions. We observed under serum monolayer conditions, that nestin positive or nestin and SMA double positive rat stromal cells outgrew EGFR amplified tumor cells, while serum spheroid cultures preserved tumor cells with EGFR amplification. Serum free suspension culture exhibited a more variable cell composition in that the resultant cell populations were either predominantly nestin/SOX2 co-expressing rat stromal cells or human tumor cells, or a mixture of both. The selection for nestin/SMA positive stromal cells under serum monolayer conditions was also consistently observed in human oligodendrogliomas and oligoastrocytomas with IDH mutations. Our results highlight for the first time that serum monolayer conditions can select for stromal cells instead of tumor cells in certain brain tumor subtypes. This result has an important impact on the establishment of new tumor cell cultures from brain tumors and raises the question of the proper conditions for the growth of the tumor cell populations of interest.
- Published
- 2013
- Full Text
- View/download PDF
41. Domains I and IV of annexin A2 affect the formation and integrity of in vitro capillary-like networks.
- Author
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Raddum AM, Evensen L, Hollås H, Grindheim AK, Lorens JB, and Vedeler A
- Subjects
- Animals, Annexin A2 pharmacology, Cattle, Cells, Cultured, Human Umbilical Vein Endothelial Cells cytology, Human Umbilical Vein Endothelial Cells drug effects, Humans, Microscopy, Confocal, Myocytes, Smooth Muscle cytology, Myocytes, Smooth Muscle drug effects, S100 Proteins metabolism, Annexin A2 metabolism, Neovascularization, Physiologic drug effects
- Abstract
Annexin A2 (AnxA2) is a widely expressed multifunctional protein found in different cellular compartments. In spite of lacking a hydrophobic signal peptide, AnxA2 is found at the cell surface of endothelial cells, indicative of a role in angiogenesis. Increased extracellular levels of AnxA2 in tumours correlate with neoangiogenesis, metastasis and poor prognosis. We hypothesised that extracellular AnxA2 may contribute to angiogenesis by affecting endothelial cell-cell interactions and motility. To address this question, we studied the effect of heterotetrameric and monomeric forms of AnxA2, as well as its two soluble domains on the formation and maintenance of capillary-like structures by using an in vitro co-culture system consisting of endothelial and smooth muscle cells. In particular, addition of purified domains I and IV of AnxA2 potently inhibited the vascular endothelial growth factor (VEGF)-dependent formation of the capillary-like networks in a dose-dependent manner. In addition, these AnxA2 domains disrupted endothelial cell-cell contacts in preformed capillary-like networks, resulting in the internalisation of vascular endothelial (VE)-cadherin and the formation of VE-cadherin-containing filopodia-like structures between the endothelial cells, suggesting increased cell motility. Addition of monoclonal AnxA2 antibodies, in particular against Tyr23 phosphorylated AnxA2, also strongly inhibited network formation in the co-culture system. These results suggest that extracellular AnxA2, most likely in its Tyr phosphorylated form, plays a pivotal role in angiogenesis. The exogenously added AnxA2 domains most likely mediate their effects by competing with endogenous AnxA2 for extracellular factors necessary for the initiation and maintenance of angiogenesis, such as those involved in the formation/integrity of cell-cell contacts.
- Published
- 2013
- Full Text
- View/download PDF
42. Image-based high-throughput screening for inhibitors of angiogenesis.
- Author
-
Evensen L, Link W, and Lorens JB
- Subjects
- Cell Culture Techniques, Cells, Cultured, Coculture Techniques, Green Fluorescent Proteins biosynthesis, Green Fluorescent Proteins genetics, Human Umbilical Vein Endothelial Cells drug effects, Humans, Microscopy, Fluorescence, Myocytes, Smooth Muscle drug effects, Pulmonary Artery cytology, Recombinant Proteins biosynthesis, Recombinant Proteins genetics, Staining and Labeling, Transduction, Genetic, Angiogenesis Inhibitors pharmacology, Benzimidazoles pharmacology, High-Throughput Screening Assays methods, Image Processing, Computer-Assisted, Phthalazines pharmacology, Pyridines pharmacology, Quinolones pharmacology
- Abstract
Automated multicolor fluorescence microscopy facilitates high-throughput quantitation of cellular parameters of complex, organotypic systems. In vitro co-cultured vascular cells form capillary-like networks that model facets of angiogenesis, making it an attractive alternative for anti-angiogenic drug discovery. We have adapted this angiogenesis assay system to a high-throughput format to enable automated image-based high-throughput screening of live primary human vascular cell co-cultures with chemical libraries for anti-angiogenic drug discovery. Protocols are described for setup of a fluorescence-based co-culture assay, live cell image acquisition, image analysis of morphological parameters, and screening data handling.
- Published
- 2013
- Full Text
- View/download PDF
43. Camptothecin-7-yl-methanthiole: semisynthesis and biological evaluation.
- Author
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Christodoulou MS, Zunino F, Zuco V, Borrelli S, Comi D, Fontana G, Martinelli M, Lorens JB, Evensen L, Sironi M, Pieraccini S, Dalla Via L, Gia OM, and Passarella D
- Subjects
- Antineoplastic Agents, Phytogenic chemical synthesis, Antineoplastic Agents, Phytogenic metabolism, Camptothecin chemical synthesis, Camptothecin metabolism, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, DNA Topoisomerases metabolism, Glutathione metabolism, Humans, Models, Molecular, Neoplasms drug therapy, Neoplasms enzymology, Prodrugs chemical synthesis, Prodrugs metabolism, Topoisomerase I Inhibitors chemical synthesis, Topoisomerase I Inhibitors chemistry, Topoisomerase I Inhibitors metabolism, Topoisomerase I Inhibitors pharmacology, Antineoplastic Agents, Phytogenic chemistry, Antineoplastic Agents, Phytogenic pharmacology, Camptothecin analogs & derivatives, Camptothecin pharmacology, Prodrugs chemistry, Prodrugs pharmacology
- Abstract
The introduction of a methylenthiol group at position 7 of camptothecin was carried out in four steps. This preparation also yielded the corresponding disulfide, which behaves as a prodrug due to its reactivity with glutathione. Assessment of their antiproliferative activities, investigations of their mechanism of action, and molecular modeling analysis indicated that the 7-modified camptothecin derivatives described herein maintain the biological activity and drug-target interactions of the parent compound., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2012
- Full Text
- View/download PDF
44. Soluble mediators released by acute myeloid leukemia cells increase capillary-like networks.
- Author
-
Hatfield KJ, Evensen L, Reikvam H, Lorens JB, and Bruserud Ø
- Subjects
- Adult, Aged, Aged, 80 and over, Coculture Techniques, Culture Media, Conditioned pharmacology, Cytokines immunology, Endothelial Cells drug effects, Endothelial Cells pathology, Female, Humans, Leukemia, Myeloid, Acute immunology, Leukemia, Myeloid, Acute pathology, Lymphocyte Activation, Male, Middle Aged, Models, Biological, Muscle, Smooth, Vascular drug effects, Muscle, Smooth, Vascular pathology, Myocytes, Smooth Muscle drug effects, Myocytes, Smooth Muscle pathology, Precursor Cell Lymphoblastic Leukemia-Lymphoma immunology, Precursor Cell Lymphoblastic Leukemia-Lymphoma metabolism, Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology, T-Lymphocytes immunology, T-Lymphocytes metabolism, Tumor Cells, Cultured, Capillaries pathology, Cytokines metabolism, Leukemia, Myeloid, Acute metabolism, Neovascularization, Pathologic
- Abstract
Increased bone marrow angiogenesis is seen in several hematological malignancies, including acute myeloid leukemia (AML). We used a co-culture assay of endothelial and vascular smooth muscle cells (vSMC) to investigate the effects of AML-conditioned medium on capillary networks. We investigated primary AML cells derived from 44 unselected patients and observed that for a large subset of patients, the constitutive cytokine release by the leukemic cells stimulated endothelial cell organization into capillary-like networks, while there were only minor or no effects for other patients. We analyzed the constitutive AML cell release of 31 cytokines for all the patients and performed a hierarchical cluster analysis of the cytokine profile which identified two major patient subsets that differed in their ability to enhance capillary-like networks; increased capillary-like networks was then associated with high constitutive release of several cytokines and especially high levels of several pro-angiogenic chemokines. Significantly increased network formation was not seen for any of the 11 acute lymphoblastic leukemia patients investigated. The cytokine response by activated normal T cells inhibited endothelial network formation in our in vitro model of angiogenesis and activated normal monocytes had only a minor influence on tube formation. Our study shows that AML-derived cytokines can induce the organization of endothelial cells into vessel-like structures., (© 2012 John Wiley & Sons A/S.)
- Published
- 2012
- Full Text
- View/download PDF
45. A combined targeted/phenotypic approach for the identification of new antiangiogenics agents active on a zebrafish model: from in silico screening to cyclodextrin formulation.
- Author
-
Radi M, Evensen L, Dreassi E, Zamperini C, Caporicci M, Falchi F, Musumeci F, Schenone S, Lorens JB, and Botta M
- Subjects
- Animals, Cyclodextrins chemistry, Drug Carriers chemistry, Embryo, Nonmammalian drug effects, Human Umbilical Vein Endothelial Cells, Humans, Models, Animal, Proto-Oncogene Proteins pp60(c-src) antagonists & inhibitors, Proto-Oncogene Proteins pp60(c-src) metabolism, Vascular Endothelial Growth Factor Receptor-2 antagonists & inhibitors, Vascular Endothelial Growth Factor Receptor-2 metabolism, Zebrafish embryology, Angiogenesis Inhibitors chemistry, Angiogenesis Inhibitors pharmacology, Drug Discovery methods, Embryo, Nonmammalian blood supply, Neovascularization, Pathologic drug therapy, Neovascularization, Physiologic drug effects
- Abstract
A combined targeted/phenotypic approach for the rapid identification of novel antiangiogenics with in vivo efficacy is herein reported. Considering the important role played by the tyrosine kinase c-Src in the regulation of tumour angiogenesis, we submitted our in-house library of c-Src inhibitors to a sequential screening approach: in silico screening on VEGFR2, in vitro screening on HUVEC cells, ADME profiling, formulation and in vivo testing on a zebrafish model. A promising antiangiogenic candidate able to interfere with the vascular growth of a zebrafish model at low micromolar concentration was thus identified., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2012
- Full Text
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46. Isosteric replacement of the Z-enone with haloethyl ketone and E-enone in a resorcylic acid lactone series and biological evaluation.
- Author
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Napolitano C, Natoni A, Santocanale C, Evensen L, Lorens JB, and Murphy PV
- Subjects
- Antineoplastic Agents chemical synthesis, Antineoplastic Agents toxicity, Cells, Cultured, Humans, Isomerism, Lactones chemical synthesis, Lactones toxicity, Protein Kinase Inhibitors chemical synthesis, Protein Kinase Inhibitors toxicity, Protein Kinases chemistry, Protein Kinases metabolism, Structure-Activity Relationship, Antineoplastic Agents chemistry, Ketones chemistry, Lactones chemistry, Protein Kinase Inhibitors chemistry
- Abstract
The synthesis of a small library of resorcylic acid lactones and evaluation of their biological properties as kinase inhibitors is described. Within the series E-enones were found more active than corresponding Z-enones as inhibitors of a subset of kinases containing a conserved cysteine. Replacement of the enone moiety with a β-haloketone group led to compounds with an interesting kinase selectivity profile and also antiproliferative activity against Jurkat cells. An E-enone derivative also showed activity against capillary tube formation based on a co-culture of primary human umbilical cord endothelial cells (HUVECs) and vascular smooth muscle cells (vSMCs)., (Copyright © 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
47. Synthesis and biological evaluation of new camptothecin derivatives obtained by modification of position 20.
- Author
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Riva E, Comi D, Borrelli S, Colombo F, Danieli B, Borlak J, Evensen L, Lorens JB, Fontana G, Gia OM, Via LD, and Passarella D
- Subjects
- Angiogenesis Inhibitors, Animals, Camptothecin analogs & derivatives, Camptothecin chemical synthesis, Camptothecin pharmacology, Caspases drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Humans, Inhibitory Concentration 50, Mice, Reactive Oxygen Species, Structure-Activity Relationship, Topoisomerase I Inhibitors chemistry, Antineoplastic Agents chemical synthesis, DNA Topoisomerases, Type I drug effects, Topoisomerase I Inhibitors chemical synthesis
- Abstract
The preparation and biological evaluation of a novel series of dimeric camptothecin derivatives are described. All the new compounds showed a significant ability to inhibit human tumor cell growth with IC(50) values ranging from 0.03 to 12.2 μM. The interference with the activity of the nuclear enzymes topoisomerases has been demonstrated, highlighting the poison effect of one of the obtained byproducts toward topoisomerase I. A moderate antiangiogenic activity has been demonstrated for one of the obtained compounds. Moreover, the effects of four new compounds on caspases activity and ROS generation have been studied on transgenic mouse cell., (Copyright © 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
48. A stroke preparedness RCT in a multi-ethnic cohort: design and methods.
- Author
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Boden-Albala B, Stillman J, Perez T, Evensen L, Moats H, Wright C, Moon-Howard J, Doyle M, and Paik MC
- Subjects
- Cohort Studies, Ethnicity, Female, Health Knowledge, Attitudes, Practice, Humans, Ischemic Attack, Transient ethnology, Male, Middle Aged, Patient Education as Topic, Prospective Studies, Stroke ethnology, Time Factors, Fibrinolytic Agents therapeutic use, Ischemic Attack, Transient drug therapy, Randomized Controlled Trials as Topic, Research Design, Stroke drug therapy, Tissue Plasminogen Activator therapeutic use
- Abstract
Background: Tissue plasminogen activator (tPA), the only approved treatment for acute ischemic stroke (IS), is significantly underutilized likely due to poor lay information about stroke as an emergency. In order to improve outcomes in acute IS, it is critical to raise awareness and recognition of stroke symptoms particularly among minority populations. This manuscript describes the application of a stroke preparedness behavioral intervention and includes baseline information in a multi-ethnic population of stroke and transient ischemic attack (TIA) survivors., Methods: In the Stroke Warning Information and Faster Treatment Study (SWIFT), we prospectively identified, and randomized IS and TIA patients to determine efficacy of a culturally tailored interactive stroke preparedness strategy. Data collected at baseline included acute stroke parameters, stroke knowledge, severity, social resources and vascular risk assessment., Results: Of the 736 enrolled to date, 76% were IS and 24% TIA events. The cohort was 51% female: 45% Hispanic, 26% White and 25% Black. Over 75% reported hypertension, 36% diabetes, and 16% cardiac disease. Mean time from onset to emergency department (ED) arrival was 46h (median 13h) differing significantly between Whites (mean 52h, median 11h) and Blacks (mean 52h, median 17h) versus Hispanics (mean 39h, median 11h). Knowledge that a stroke occurs in the brain differed significantly by between Whites (85%), Blacks (64%), Hispanics (66%, p<0.000)., Conclusions: Disparities remain in both action and knowledge surrounding acute stroke. Use of written information has not proven an effective means of changing health behaviors. We propose an interactive culturally tailored intervention to address behavioral change in acute stroke., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
49. Imaged-based high-throughput screening for anti-angiogenic drug discovery.
- Author
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Evensen L, Link W, and Lorens JB
- Subjects
- Animals, Coculture Techniques, Humans, Muscle, Smooth, Vascular cytology, Angiogenesis Inhibitors therapeutic use, Drug Discovery
- Abstract
Recent developments in high-content screening (HCS) technologies make it an attractive alternative for anti-angiogenic drug discovery. HCS integrates high-throughput methodologies with automated multicolor fluorescence microscopy to collect quantitative morphological and molecular data from complex biological systems. Organotypic systems based on primary vascular cells model many facets of angiogenesis. The adaptation of these complex in vitro assay systems to high-throughput HCS formats with automated image acquisition enables large-scale chemical library screening campaigns. These HCS principles can be extended further to allow small molecule compounds in in vivo model organisms such as zebrafish. In this review we discuss the latest developments within automated image-based high-throughput screening of chemical libraries for anti-angiogenic compounds.
- Published
- 2010
- Full Text
- View/download PDF
50. A novel imaging-based high-throughput screening approach to anti-angiogenic drug discovery.
- Author
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Evensen L, Micklem DR, Link W, and Lorens JB
- Subjects
- Coculture Techniques, Dose-Response Relationship, Drug, Humans, Inhibitory Concentration 50, Angiogenesis Inhibitors chemistry, Drug Discovery methods, High-Throughput Screening Assays methods
- Abstract
The successful progression to the clinic of angiogenesis inhibitors for cancer treatment has spurred interest in developing new classes of anti-angiogenic compounds. The resulting surge in available candidate therapeutics highlights the need for robust, high-throughput angiogenesis screening systems that adequately capture the complexity of new vessel formation while providing quantitative evaluation of the potency of these agents. Available in vitro angiogenesis assays are either cumbersome, impeding adaptation to high-throughput screening formats, or inadequately model the complex multistep process of new vessel formation. We therefore developed an organotypic endothelial-mural cell co-culture assay system that reflects several facets of angiogenesis while remaining compatible with high-throughput/high-content image screening. Co-culture of primary human endothelial cells (EC) and vascular smooth muscle cells (vSMC) results in assembly of a network of tubular endothelial structures enveloped with vascular basement membrane proteins, thus, comprising the three main components of blood vessels. Initially, EC are dependent on vSMC-derived VEGF and sensitive to clinical anti-angiogenic therapeutics. A subsequent phenotypic VEGF-switch renders EC networks resistant to anti-VEGF therapeutics, demarcating a mature vascular phenotype. Conversely, mature EC networks remain sensitive to vascular disrupting agents. Therefore, candidate anti-angiogenic compounds can be interrogated for their relative potency on immature and mature networks and classified as either vascular normalizing or vascular disrupting agents. Here, we demonstrate that the EC-vSMC co-culture assay represents a robust high-content imaging high-throughput screening system for identification of novel anti-angiogenic agents. A pilot high-throughput screening campaign was used to define informative imaging parameters and develop a follow-up dose-response scheme for hit characterization. High-throughput screening using the EC-vSMC co-culture assay establishes a new platform to screen for novel anti-angiogenic compounds for cancer therapy.
- Published
- 2010
- Full Text
- View/download PDF
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