Neuronal inhibition and synaptic plasticity of basal ganglia neurons in Parkinson's disease

PubMed Central

Milosevic, Luka; Kalia, Suneil K; Hodaie, Mojgan; Lozano, Andres M; Fasano, Alfonso; Popovic, Milos R; Hutchison, William D

2018-01-01

Abstract Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson’s disease symptoms. The therapeutic benefits of deep brain stimulation are frequency-dependent, but the underlying physiological mechanisms remain unclear. To advance deep brain stimulation therapy an understanding of fundamental mechanisms is critical. The objectives of this study were to (i) compare the frequency-dependent effects on cell firing in subthalamic nucleus and substantia nigra pars reticulata; (ii) quantify frequency-dependent effects on short-term plasticity in substantia nigra pars reticulata; and (iii) investigate effects of continuous long-train high frequency stimulation (comparable to conventional deep brain stimulation) on synaptic plasticity. Two closely spaced (600 µm) microelectrodes were advanced into the subthalamic nucleus (n = 27) and substantia nigra pars reticulata (n = 14) of 22 patients undergoing deep brain stimulation surgery for Parkinson’s disease. Cell firing and evoked field potentials were recorded with one microelectrode during stimulation trains from the adjacent microelectrode across a range of frequencies (1–100 Hz, 100 µA, 0.3 ms, 50–60 pulses). Subthalamic firing attenuated with ≥20 Hz (P < 0.01) stimulation (silenced at 100 Hz), while substantia nigra pars reticulata decreased with ≥3 Hz (P < 0.05) (silenced at 50 Hz). Substantia nigra pars reticulata also exhibited a more prominent increase in transient silent period following stimulation. Patients with longer silent periods after 100 Hz stimulation in the subthalamic nucleus tended to have better clinical outcome after deep brain stimulation. At ≥30 Hz the first evoked field potential of the stimulation train in substantia nigra pars reticulata was potentiated (P < 0.05); however, the average amplitude of the subsequent potentials was rapidly attenuated (P < 0.01). This is suggestive of synaptic facilitation followed by rapid depression. Paired pulse ratios calculated at the beginning of the train revealed that 20 Hz (P < 0.05) was the minimum frequency required to induce synaptic depression. Lastly, the average amplitude of evoked field potentials during 1 Hz pulses showed significant inhibitory synaptic potentiation after long-train high frequency stimulation (P < 0.001) and these increases were coupled with increased durations of neuronal inhibition (P < 0.01). The subthalamic nucleus exhibited a higher frequency threshold for stimulation-induced inhibition than the substantia nigra pars reticulata likely due to differing ratios of GABA:glutamate terminals on the soma and/or the nature of their GABAergic inputs (pallidal versus striatal). We suggest that enhancement of inhibitory synaptic plasticity, and frequency-dependent potentiation and depression are putative mechanisms of deep brain stimulation. Furthermore, we foresee that future closed-loop deep brain stimulation systems (with more frequent off stimulation periods) may benefit from inhibitory synaptic potentiation that occurs after high frequency stimulation. PMID:29236966

Intense laser pulse propagation in capillary discharge plasma channels

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

Hubbard, R. F.; Moore, C. I.; Sprangle, P.

Optical guiding of intense laser pulses is required for plasma-based accelerator concepts such as the laser wakefield accelerator. Reported experiments have successfully transported intense laser pulses in the hollow plasma column produced by a capillary discharge. The hollow plasma has an index of refraction which peaks on-axis, thus providing optical guiding which overcomes beam expansion due to diffraction. In more recent experiments at Hebrew University, 800 nm wavelength, 0.1 mJ, 100 fs pulses have been guided in {approx}300 micron radius capillaries over distances as long as 6.6 cm. Simulations of these experiments using a 2-D nonlinear laser propagation model producemore » the expected optical guiding, with the laser pulse radius r{sub L} exhibiting oscillations about the equilibrium value predicted by an analytical envelope equation model. The oscillations are damped at the front of the pulse and grow in amplitude in the back of the pulse. This growth and damping is attributed to finite pulse length effects. Simulations also show that further ionization of the discharge plasma by the laser pulse may hollow the laser pulse and introduce modulations in the spot size. This ionization-defocusing effect is expected to be significant at the high intensities required for accelerator application. Capillary discharge experiments at much higher intensities are in progress on the Naval Research Laboratory T{sup 3} laser, and preliminary results are reported.« less

Analysis of non-Gaussian laser mode guidance and evolution in leaky plasma channels

NASA Astrophysics Data System (ADS)

Djordjevic, Blagoje; Benedetti, Carlo; Schroeder, Carl; Esarey, Eric; Leemans, Wim

2016-10-01

The evolution and propagation of a non-Gaussian laser pulse under varying circumstances, including a typical matched parabolic channel as well as leaky channels, are investigated. It has previously been shown for a Gaussian pulse that matched guiding can be achieved using parabolic plasma channels. In the low power regime, it can be shown directly that for multi-mode pulses there is significant transverse beating. Given the adverse behavior of non-Gaussian pulses in traditional guiding designs, we examine the use of leaky channels to filter out higher modes as a means of optimizing laser conditions. The interaction between different modes can have an adverse effect on the laser pulse as it propagates through the primary channel. To improve guiding of the pulse we propose using leaky channels. Realistic plasma channel profiles are considered. Higher order mode content is lost through the leaky channel, while the fundamental mode remains well-guided. This is demonstrated using both numerical simulations as well as the source-dependent Laguerre-Gaussian modal expansion. In conclusion, an idealized plasma lens based on leaky channels is found to filter out the higher order modes and leave a near-Gaussian profile before the pulse enters the primary channel.

Intense laser pulse propagation in capillary discharge plasma channels

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

Hubbard, R.F.; Moore, C.I.; Sprangle, P.

Optical guiding of intense laser pulses is required for plasma-based accelerator concepts such as the laser wakefield accelerator. Reported experiments have successfully transported intense laser pulses in the hollow plasma column produced by a capillary discharge. The hollow plasma has an index of refraction which peaks on-axis, thus providing optical guiding which overcomes beam expansion due to diffraction. In more recent experiments at Hebrew University, 800 nm wavelength, 0.1 mJ, 100 fs pulses have been guided in {approximately}300 micron radius capillaries over distances as long as 6.6 cm. Simulations of these experiments using a 2-D nonlinear laser propagation model producemore » the expected optical guiding, with the laser pulse radius r{sub L} exhibiting oscillations about the equilibrium value predicted by an analytical envelope equation model. The oscillations are damped at the front of the pulse and grow in amplitude in the back of the pulse. This growth and damping is attributed to finite pulse length effects. Simulations also show that further ionization of the discharge plasma by the laser pulse may hollow the laser pulse and introduce modulations in the spot size. This ionization-defocusing effect is expected to be significant at the high intensities required for accelerator application. Capillary discharge experiments at much higher intensities are in progress on the Naval Research Laboratory T{sup 3} laser, and preliminary results are reported. {copyright} {ital 1999 American Institute of Physics.}« less

Indigenous Storytelling and Participatory Action Research

PubMed Central

2015-01-01

Storytelling, in its various forms, has often been described as a practice with great emancipatory potential. In turn, Indigenous knowledge shows great promise in guiding a participatory action research (PAR) methodology. Yet these two approaches are rarely discussed in relation to one another, nor, has much been written in terms of how these two approaches may work synergistically toward a decolonizing research approach. In this article, I report on a community-driven knowledge translation activity, the Peoples’ International Health Tribunal, as an exemplar of how narrative and PAR approaches, guided by local Indigenous knowledge, have great potential to build methodologically and ethically robust research processes. Implications for building globally relevant research alliances and scholarship are further discussed, particularly in relation to working with Indigenous communities. PMID:28462305

Guiding of Long-Distance Electric Discharges by Combined Femtosecond and Nanosecond Pulses Emitted by Hybrid KrF Laser System

DTIC Science & Technology

2014-01-30

AFRL-AFOSR-UK-TR-2014-0040 Guiding of long-distance electric discharges by combined femtosecond and nanosecond pulses emitted by...To) 27 September 2010 – 31 December 2013 4. TITLE AND SUBTITLE Guiding of long-distance electric discharges by combined femtosecond and...plasma channels in the atmosphere and laser guiding of high-voltage electric discharges . 15. SUBJECT TERMS EOARD, triggering

Ionization assisted self-guiding of femtosecond laser pulses

NASA Astrophysics Data System (ADS)

Morozov, A.; Goltsov, A.; Chen, Q.; Scully, M.; Suckewer, S.

2018-05-01

We propose a new mechanism for the self-guiding of ultra-intense sub-picosecond laser pulses in gaseous media. It can be realized via optical field ionization by a laser pulse as it propagates inside an expanding cylindrical shock wave launched into ambient gas by a decayed plasma filament. In experiments, the filament was created in a hydrogen jet by a low energy femtosecond laser pre-pulse line focused with axicon lens. We demonstrated ionization-assisted guiding in structures with diameter as small as 14 μm and up to 3.5 mm long. The intensity reached 5 × 1017 W/cm2 in a single mode propagating for more than 100 Rayleigh lengths.

Laser pulse coded signal frequency measuring device based on DSP and CPLD

NASA Astrophysics Data System (ADS)

Zhang, Hai-bo; Cao, Li-hua; Geng, Ai-hui; Li, Yan; Guo, Ru-hai; Wang, Ting-feng

2011-06-01

Laser pulse code is an anti-jamming measures used in semi-active laser guided weapons. On account of the laser-guided signals adopting pulse coding mode and the weak signal processing, it need complex calculations in the frequency measurement process according to the laser pulse code signal time correlation to meet the request in optoelectronic countermeasures in semi-active laser guided weapons. To ensure accurately completing frequency measurement in a short time, it needed to carry out self-related process with the pulse arrival time series composed of pulse arrival time, calculate the signal repetition period, and then identify the letter type to achieve signal decoding from determining the time value, number and rank number in a signal cycle by Using CPLD and DSP for signal processing chip, designing a laser-guided signal frequency measurement in the pulse frequency measurement device, improving the signal processing capability through the appropriate software algorithms. In this article, we introduced the principle of frequency measurement of the device, described the hardware components of the device, the system works and software, analyzed the impact of some system factors on the accuracy of the measurement. The experimental results indicated that this system improve the accuracy of the measurement under the premise of volume, real-time, anti-interference, low power of the laser pulse frequency measuring device. The practicality of the design, reliability has been demonstrated from the experimental point of view.

Indigenous Storytelling and Participatory Action Research: Allies Toward Decolonization? Reflections From the Peoples' International Health Tribunal.

PubMed

Caxaj, C Susana

2015-01-01

Storytelling, in its various forms, has often been described as a practice with great emancipatory potential. In turn, Indigenous knowledge shows great promise in guiding a participatory action research (PAR) methodology. Yet these two approaches are rarely discussed in relation to one another, nor, has much been written in terms of how these two approaches may work synergistically toward a decolonizing research approach. In this article, I report on a community-driven knowledge translation activity, the Peoples' International Health Tribunal, as an exemplar of how narrative and PAR approaches, guided by local Indigenous knowledge, have great potential to build methodologically and ethically robust research processes. Implications for building globally relevant research alliances and scholarship are further discussed, particularly in relation to working with Indigenous communities.

Guiding out-migrating juvenile sea lamprey (Petromyzon marinus) with pulsed direct current

USGS Publications Warehouse

Johnson, Nicholas S.; Miehls, Scott M.

2014-01-01

Non-physical stimuli can deter or guide fish without affecting water flow or navigation and therefore have been investigated to improve fish passage at anthropogenic barriers and to control movement of invasive fish. Upstream fish migration can be blocked or guided without physical structure by electrifying the water, but directional downstream fish guidance with electricity has received little attention. We tested two non-uniform pulsed direct current electric systems, each having different electrode orientations (vertical versus horizontal), to determine their ability to guide out-migrating juvenile sea lamprey (Petromyzon marinus) and rainbow trout (Oncorhynchus mykiss). Both systems guided significantly more juvenile sea lamprey to a specific location in our experimental raceway when activated than when deactivated, but guidance efficiency decreased at the highest water velocities tested. At the electric field setting that effectively guided sea lamprey, rainbow trout were guided by the vertical electrode system, but most were blocked by the horizontal electrode system. Additional research should characterize the response of other species to non-uniform fields of pulsed DC and develop electrode configurations that guide fish over a range of water velocity.

Identification of a New Epitope in uPAR as a Target for the Cancer Therapeutic Monoclonal Antibody ATN-658, a Structural Homolog of the uPAR Binding Integrin CD11b (αM)

PubMed Central

Wei, Ying; Donate, Fernando; Juarez, Jose; Parry, Graham; Chen, Liqing; Meehan, Edward J.; Ahn, Richard W.; Ugolkov, Andrey; Dubrovskyi, Oleksii; O'Halloran, Thomas V.; Huang, Mingdong; Mazar, Andrew P.

2014-01-01

The urokinase plasminogen activator receptor (uPAR) plays a role in tumor progression and has been proposed as a target for the treatment of cancer. We recently described the development of a novel humanized monoclonal antibody that targets uPAR and has anti-tumor activity in multiple xenograft animal tumor models. This antibody, ATN-658, does not inhibit ligand binding (i.e. uPA and vitronectin) to uPAR and its mechanism of action remains unclear. As a first step in understanding the anti-tumor activity of ATN-658, we set out to identify the epitope on uPAR to which ATN-658 binds. Guided by comparisons between primate and human uPAR, epitope mapping studies were performed using several orthogonal techniques. Systematic site directed and alanine scanning mutagenesis identified the region of aa 268–275 of uPAR as the epitope for ATN-658. No known function has previously been attributed to this epitope Structural insights into epitope recognition were obtained from structural studies of the Fab fragment of ATN-658 bound to uPAR. The structure shows that the ATN-658 binds to the DIII domain of uPAR, close to the C-terminus of the receptor, corroborating the epitope mapping results. Intriguingly, when bound to uPAR, the complementarity determining region (CDR) regions of ATN-658 closely mimic the binding regions of the integrin CD11b (αM), a previously identified uPAR ligand thought to be involved in leukocyte rolling, migration and complement fixation with no known role in tumor progression of solid tumors. These studies reveal a new functional epitope on uPAR involved in tumor progression and demonstrate a previously unrecognized strategy for the therapeutic targeting of uPAR. PMID:24465541

EMPTAC (Electromagnetic Pulse Test Aircraft) user's guide

NASA Astrophysics Data System (ADS)

Cleaveland, Dale R.; Burkhard, Avery

1988-04-01

This guide was established to give test managers a way to familiarize themselves with the Air Force Weapons Laboratory's electromagnetic pulse (EMP) test aircraft program located at Kirtland Air Force Base (KAFB), New Mexico. Brief descriptions of the available EMP test facilities at KAFB are also included. This guide should give prospective customers (users) adequate information to scope the magnitude of their test effort and to accomplish general planning without extensive involvement in test execution details.

Spectral evolution of distributed feedback laser of gold nanoparticles doped solid-state dye laser medium

NASA Astrophysics Data System (ADS)

An, N. T. M.; Lien, N. T. H.; Hoang, N. D.; Nghia, N. T.; Hoa, D. Q.

2017-10-01

Characteristics of suppressed relaxation oscillation of a distributed feedback dye laser (DFDL) based on the energy transfer process in a mixture of spherical gold nanoparticles-doped solid-state polymethylmetacrylate dissolved 4-(Dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran dye was theoretically and experimentally studied. Single pulse generation regime of the DFDL can be obtained with a suitable gold nanoparticle concentration and ratio of pump power over lasing threshold. Numerical analysis and experimental approach showed that in this regime, the first-pulse laser pulsewidth is rather unchanged while varying the gold nanoparticles concentration in the range of 2.0 × 109-2.0 × 1010 par cm-3. The enhancement of first pulse and the suppression of the secondary pulses by bi-direction energy transfer of spherical gold nanoparticles were experimentally observed.

Pionic Fusion of 4He +12 C

NASA Astrophysics Data System (ADS)

Zarrella, Andrew; Yennello, Sherry

2017-09-01

Pionic fusion is the process by which two nuclei fuse and then deexcite by the exclusive emission of a pion. These reactions represent the most extreme examples of deep subthreshold pion production and provide evidence for an unknown, collective mechanism for pion production. An experiment was performed at the Texas A&M University Cyclotron Institute to measure the cross section of the 4He +12 C -> 16N +π+ reaction. The Momentum Achromat Recoil Spectrometer (MARS) was used to separate and identify the 16N fusion residues and the newly constructed Partial Truncated Icosahedron (ParTI) phoswich array was used to identify charged pions. The detector responses for each phoswich unit were recorded using fast-sampling ADCs which allow all light charged particles in the ParTI phoswiches to be identified using ``fast vs. slow'' pulse shape discrimination. By writing the waveform responses, pions can also be identified by the presence of a characteristic muon decay pulse. The combination of the residue-pion coincidence and the two independent pion identification techniques represent a highly sensitive experimental design for studying pionic fusion reactions.

[Flexible Guidance of Ultra-Short Laser Pulses in Ophthalmic Therapy Systems].

PubMed

Blum, J; Blum, M; Rill, M S; Haueisen, J

2017-01-01

In the last 20 years, the role of ultrashort pulsed lasers in ophthalmology has become increasingly important. However, it is still impossible to guide ultra-short laser pulses with standard glass fibres. The highly energetic femtosecond pulses would destroy the fibre material, and non-linear dispersion effects would significantly change beam parameters. In contrast, photonic crystal fibres mainly guide the laser pulses in air, so that absorption and dispersive pulse broadening have essentially no effect. This article compares classical beam guidance with mirrors, lenses and prisms with photonic crystal fibres and describes the underlying concepts and the current state of technology. A classical mirror arm possesses more variable optical properties, while the HCF (Hollow-Core Photonic Crystal Fibre) must be matched in terms of the laser energy and the laser spectrum. In contrast, the HCF has more advantages in respect of handling, system integration and costs. For applications based on photodisruptive laser-tissue interaction, the relatively low damage threshold of photonic crystal fibres compared to classic beam guiding systems is unacceptable. If, however, pulsed laser radiation has a sufficiently low peak intensity, e.g. as used for plasma-induced ablation, photonic crystal fibres can definitely be considered as an alternative solution to classic beam guidance. Georg Thieme Verlag KG Stuttgart · New York.

Taxonomic circumscription of Adenomera martinezi (Bokermann, 1956) (Anura: Leptodactylidae: Leptodactylinae) with the recognition of a new cryptic taxon through a bioacoustic approach.

PubMed

De Carvalho, Thiago Ribeiro; Giaretta, Ariovaldo Antonio

2013-01-01

In this paper, we provide a taxonomic circumscription of Adenomera martinezi from its type locality (Cachimbo, southwestern State of Pará) since its description (57 years ago) based on a newly collected series of eleven adult topotypes, and through a bioacoustic approach, recognize an undescribed cryptic taxon under this nominal species, which is widely distributed in central and northern Brazil. Adenomera martinezi and Adenomera saci sp. nov. can be diagnosed from all congeners by their distinctive 4-6 symmetrically arranged rows of longitudinal dark-colored spots on dorsum. They differ from each other through advertisement call structure, pulsed in Adenomera martinezi (audibly pulsed to the human ear), and non-pulsed in Adenomera saci sp. nov. (a whistle to the human ear). The recognition of Adenomera saci sp. nov. has conservation implications. Based on our assumed distribution of A. martinezi and A denomera saci sp. nov., the IUCN conservation status of A. martinezi requires a reassessment, inasmuch as we herein reconsider this species, as far as we know, as endemic to Cachimbo, southwestern State of Pará, Brazil. The 2004 extinction risk assessment included both A. martinezi and Adenomera saci sp. nov., and the conservation status category of 'Least Concern' might only be applied to Adenomera saci sp. nov., a widely distributed and abundant species in central and northern Brazil.

Nigral stimulation for resistant axial motor impairment in Parkinson's disease? A randomized controlled trial.

PubMed

Weiss, Daniel; Walach, Margarete; Meisner, Christoph; Fritz, Melanie; Scholten, Marlieke; Breit, Sorin; Plewnia, Christian; Bender, Benjamin; Gharabaghi, Alireza; Wächter, Tobias; Krüger, Rejko

2013-07-01

Gait and balance disturbances typically emerge in advanced Parkinson's disease with generally limited response to dopaminergic medication and subthalamic nucleus deep brain stimulation. Therefore, advanced programming with interleaved pulses was put forward to introduce concomittant nigral stimulation on caudal contacts of a subthalamic lead. Here, we hypothesized that the combined stimulation of subthalamic nucleus and substantia nigra pars reticulata improves axial symptoms compared with standard subthalamic nucleus stimulation. Twelve patients were enrolled in this 2 × 2 cross-over double-blind randomized controlled clinical trial and both the safety and efficacy of combined subthalamic nucleus and substantia nigra pars reticulata stimulation were evaluated compared with standard subthalamic nucleus stimulation. The primary outcome measure was the change of a broad-scaled cumulative axial Unified Parkinson's Disease Rating Scale score (Scale II items 13-15, Scale III items 27-31) at '3-week follow-up'. Secondary outcome measures specifically addressed freezing of gait, balance, quality of life, non-motor symptoms and neuropsychiatric symptoms. For the primary outcome measure no statistically significant improvement was observed for combined subthalamic nucleus and substantia nigra pars reticulata stimulation at the '3-week follow-up'. The secondary endpoints, however, revealed that the combined stimulation of subthalamic nucleus and substantia nigra pars reticulata might specifically improve freezing of gait, whereas balance impairment remained unchanged. The combined stimulation of subthalamic nucleus and substantia nigra pars reticulata was safe, and of note, no clinically relevant neuropsychiatric adverse effect was observed. Patients treated with subthalamic nucleus and substantia nigra pars reticulata stimulation revealed no 'global' effect on axial motor domains. However, this study opens the perspective that concomittant stimulation of the substantia nigra pars reticulata possibly improves otherwise resistant freezing of gait and, therefore, highly warrants a subsequent phase III randomized controlled trial.

Fluoroquinolone Resistance in Streptococcus dysgalactiae subsp. equisimilis and Evidence for a Shared Global Gene Pool with Streptococcus pyogenes▿

PubMed Central

Pinho, M. D.; Melo-Cristino, J.; Ramirez, M.

2010-01-01

Quinolone resistance is an emerging problem in Streptococcus pyogenes, and recombination with Streptococcus dysgalactiae DNA has been implicated as a frequent mechanism leading to resistance. We have characterized a collection of S. dysgalactiae subsp. equisimilis isolates responsible for infections in humans (n = 314) and found a high proportion of levofloxacin-resistant isolates (12%). Resistance was associated with multiple emm types and genetic lineages, as determined by pulsed-field gel electrophoretic profiling. Since we could not find evidence for a role of efflux pumps in resistance, we sequenced the quinolone resistance-determining regions of the gyrA and parC genes of representative resistant and susceptible isolates. We found much greater diversity among the parC genes (19 alleles) than among the gyrA genes (5 alleles). While single mutations in either GyrA or ParC were sufficient to raise the MIC so that the strains were classified as intermediately resistant, higher-level resistance was associated with mutations in both GyrA and ParC. Evidence for recombination with S. pyogenes DNA was found in some parC alleles, but this was not exclusively associated with resistance. Our data support the existence of a common reservoir of genes conferring quinolone resistance shared between S. dysgalactiae subsp. equisimilis and S. pyogenes, while no recombination with the animal pathogen S. dysgalactiae subsp. dysgalactiae could be found. PMID:20145082

Ciprofloxacin-resistant Salmonella enterica Serotype Typhi, United States, 1999-2008.

PubMed

Medalla, Felicita; Sjölund-Karlsson, Maria; Shin, Sanghyuk; Harvey, Emily; Joyce, Kevin; Theobald, Lisa; Nygren, Benjamin N; Pecic, Gary; Gay, Kathryn; Austin, Jana; Stuart, Andrew; Blanton, Elizabeth; Mintz, Eric D; Whichard, Jean M; Barzilay, Esra J

2011-06-01

We report 9 ciprofloxacin-resistant Salmonella enterica serotype Typhi isolates submitted to the US National Antimicrobial Resistance Monitoring System during 1999-2008. The first 2 had indistinguishable pulsed-field gel electrophoresis patterns and identical gyrA and parC mutations. Eight of the 9 patients had traveled to India within 30 days before illness onset.

Filtering higher-order laser modes using leaky plasma channels

NASA Astrophysics Data System (ADS)

Djordjević, B. Z.; Benedetti, C.; Schroeder, C. B.; Esarey, E.; Leemans, W. P.

2018-01-01

Plasma structures based on leaky channels are proposed to filter higher-order laser mode content. The evolution and propagation of non-Gaussian laser pulses in leaky channels are studied, and it is shown that, for appropriate laser-plasma parameters, the higher-order laser mode content of the pulse may be removed while the fundamental mode remains well-guided. The behavior of multi-mode laser pulses is described analytically and numerically using envelope equations, including the derivation of the leakage coefficients, and compared to particle-in-cell simulations. Laser pulse propagation, with reduced higher-order mode content, improves guiding in parabolic plasma channels, enabling extended interaction lengths for laser-plasma accelerator applications.

Pulse pressure variation-guided fluid therapy after cardiac surgery: a pilot before-and-after trial.

PubMed

Suzuki, Satoshi; Woinarski, Nicholas C Z; Lipcsey, Miklos; Candal, Cristina Lluch; Schneider, Antoine G; Glassford, Neil J; Eastwood, Glenn M; Bellomo, Rinaldo

2014-12-01

The aim of this study is to study the feasibility, safety, and physiological effects of pulse pressure variation (PPV)-guided fluid therapy in patients after cardiac surgery. We conducted a pilot prospective before-and-after study during mandatory ventilation after cardiac surgery in a tertiary intensive care unit. We introduced a protocol to deliver a fluid bolus for a PPV≥13% for at least >10 minutes during the intervention period. We studied 45 control patients and 53 intervention patients. During the intervention period, clinicians administered a fluid bolus on 79% of the defined PPV trigger episodes. Median total fluid intake was similar between 2 groups during mandatory ventilation (1297 mL [interquartile range 549-1968] vs 1481 mL [807-2563]; P=.17) and the first 24 hours (3046 mL [interquartile range 2317-3982] vs 3017 mL [2192-4028]; P=.73). After adjusting for several baseline factors, PPV-guided fluid management significantly increased fluid intake during mandatory ventilation (P=.004) but not during the first 24 hours (P=.47). Pulse pressure variation-guided fluid therapy, however, did not significantly affect hemodynamic, renal, and metabolic variables. No serious adverse events were noted. Pulse pressure variation-guided fluid management was feasible and safe during mandatory ventilation after cardiac surgery. However, its advantages may be clinically small. Copyright © 2014 Elsevier Inc. All rights reserved.

Filamentation in Air with Ultrashort Mid-Infrared Pulses

DTIC Science & Technology

2011-05-09

remote sensing [11, 12], lightning guiding [13–15], supercontinuum generation ( SCG ) [16], pulse compression [17], and THz generation [18]. Although...shock) and push the pulse toward positive times [23, 24, 46, 54, 55] [see Fig. 3(a) at ζ = 0.6]. Subsequently, the pulse collapses at ζ = 0.9, and SCG

Ciprofloxacin-Resistant Salmonella enterica Serotype Typhi, United States, 1999–2008

PubMed Central

Sjölund-Karlsson, Maria; Shin, Sanghyuk; Harvey, Emily; Joyce, Kevin; Theobald, Lisa; Nygren, Benjamin L.; Pecic, Gary; Gay, Kathryn; Austin, Jana; Stuart, Andrew; Blanton, Elizabeth; Mintz, Eric D.; Whichard, Jean M.; Barzilay, Ezra J.

2011-01-01

We report 9 ciprofloxacin-resistant Salmonella enterica serotype Typhi isolates submitted to the US National Antimicrobial Resistance Monitoring System during 1999–2008. The first 2 had indistinguishable pulsed-field gel electrophoresis patterns and identical gyrA and parC mutations. Eight of the 9 patients had traveled to India within 30 days before illness onset. PMID:21749779

Air-guided photonic-crystal-fiber pulse-compression delivery of multimegawatt femtosecond laser output for nonlinear-optical imaging and neurosurgery

NASA Astrophysics Data System (ADS)

Lanin, Aleksandr A.; Fedotov, Il'ya V.; Sidorov-Biryukov, Dmitrii A.; Doronina-Amitonova, Lyubov V.; Ivashkina, Olga I.; Zots, Marina A.; Sun, Chi-Kuang; Ömer Ilday, F.; Fedotov, Andrei B.; Anokhin, Konstantin V.; Zheltikov, Aleksei M.

2012-03-01

Large-core hollow photonic-crystal fibers (PCFs) are shown to enable a fiber-format air-guided delivery of ultrashort infrared laser pulses for neurosurgery and nonlinear-optical imaging. With an appropriate dispersion precompensation, an anomalously dispersive 15-μm-core hollow PCF compresses 510-fs, 1070-nm light pulses to a pulse width of about 110 fs, providing a peak power in excess of 5 MW. The compressed PCF output is employed to induce a local photodisruption of corpus callosum tissues in mouse brain and is used to generate the third harmonic in brain tissues, which is captured by the PCF and delivered to a detector through the PCF cladding.

Cartographie T

NASA Astrophysics Data System (ADS)

Cote, Jean-Charles

Les cartographies T1 par séquences d'échos stimulés et Look- Locker sont les plus communément utilisées pour mesurer les temps de relaxation T 1 en imagerie par résonance magnétique (IRM). Elles ont des performances d'usage clinique, ne prenant que quelques minutes pour produire une carte des valeurs de T1. Ces séquences demeurent cependant très sensibles à la précision des pulses radiofréquences (RF) qui réorientent l'aimantation pour produire les signaux mesurés. Les pulses RF rectangulaires régulièrement utilisés en IRM produisent un basculement de l'aimantation directement proportionnel à l'intensité du champ magnétique B 1 produit par l'antenne émettrice. Les antennes cliniques ont des distributions de champs B1 qui fluctuent énormément. En exemple, l'antenne servant à produire des images de la tête possède un champ B1 qui est distribué dans son volume utile sur une plage allant de 0,5 à 1,2 relativement à son centre. Cette variation spatiale de B1 entraîne des erreurs systématiques sur les valeurs ajustées de T1 dépassant les 50%. Le développement d'un nouveau concept d'excitation RF à approche tangentielle ayant des propriétés adiabatiques pouvant remplacer les demi-passages adiabatiques (AHP) et son utilisation sous la forme d'un BIR-4-S2 (B1-Insensitive Rotation-4 AHP-Sequentialized 2 steps) dans les séquences de cartographie T1 a permis de réduire à moins de 10% les erreurs systématiques dans le cas mesuré par échos stimulés compensés et à moins de 5% pour le Look-Locker. Le BIR-4-S2 possède une imprécision sur l'angle de basculement de moins de 5° sur une plage relative allant de 0,75 à 1,75 autour d'un champ de référence B1 ref, pour un choix de basculement sur 360°. Et, contrairement aux pulses adiabatiques, il demeure un pulse RF tridimentionnel (3D) à faible puissance pouvant être utilisé à répétition cliniquement sans risque d'échauffement dangereux pour les patients. La séquence d'échos stimulés compensés dont nous avons parlé ci-haut utilise un autre de nos développements: la compensation. Le signal produit par une séquence traditionnelle d'échos stimulés tend vers zéro en suivant la relaxation T1 dans le temps. Parfois ceci cause des problèmes lorsque le signal des derniers échos commence à être influencé par le bruit. La compensation a pour effet de modifier la décroissance exponentielle du signal. Ce changement s'opère en tenant compte de la relaxation T1 lors du calcul des angles de basculement nécessaire à la séquence. La compensation transfère une partie de la demande du volume de signal des premiers échos vers les derniers. On peut compenser entièrement et ainsi programmer une séquence qui produira des signaux égaux entre tous les échos ou compenser partiellement pour soutenir les signaux des derniers échos en conservant un maximum de signal total.

Data acquisition system

DOEpatents

Phillips, David T.

1979-01-01

A data acquisition system capable of resolving transient pulses in the subnanosecond range. A pulse in an information carrying medium such as light is transmitted through means which disperse the pulse, such as a fiber optic light guide which time-stretches optical pulses by chromatic dispersion. This time-stretched pulse is used as a sampling pulse and is modulated by the signal to be recorded. The modulated pulse may be further time-stretched prior to being recorded. The recorded modulated pulse is unfolded to derive the transient signal by utilizing the relationship of the time-stretching that occurred in the original pulse.

Pure-phase selective excitation in fast-relaxing systems.

PubMed

Zangger, K; Oberer, M; Sterk, H

2001-09-01

Selective pulses have been used frequently for small molecules. However, their application to proteins and other macromolecules has been limited. The long duration of shaped-selective pulses and the short T(2) relaxation times in proteins often prohibited the use of highly selective pulses especially on larger biomolecules. A very selective excitation can be obtained within a short time by using the selective excitation sequence presented in this paper. Instead of using a shaped low-intensity radiofrequency pulse, a cluster of hard 90 degrees pulses, delays of free precession, and pulsed field gradients can be used to selectively excite a narrow chemical shift range within a relatively short time. Thereby, off-resonance magnetization, which is allowed to evolve freely during the free precession intervals, is destroyed by the gradient pulses. Off-resonance excitation artifacts can be removed by random variation of the interpulse delays. This leads to an excitation profile with selectivity as well as phase and relaxation behavior superior to that of commonly used shaped-selective pulses. Since the evolution of scalar coupling is inherently suppressed during the double-selective excitation of two different scalar-coupled nuclei, the presented pulse cluster is especially suited for simultaneous highly selective excitation of N-H and C-H fragments. Experimental examples are demonstrated on hen egg white lysozyme (14 kD) and the bacterial antidote ParD (19 kD). Copyright 2001 Academic Press.

Tolerance of chufa (Cyperus esculentus L.) plants, representing the higher plant compartment in bioregenerative life support systems, to super-optimal air temperatures

NASA Astrophysics Data System (ADS)

Shklavtsova, E. S.; Ushakova, S. A.; Shikhov, V. N.; Anishchenko, O. V.

2013-01-01

Plants intended to be included in the photosynthesizing compartment of the bioregenerative life support system (BLSS) need to be studied in terms of both their production parameters under optimal conditions and their tolerance to stress factors that might be caused by emergency situations. The purpose of this study was to investigate tolerance of chufa (Cyperus esculentus L.) plants to the super-optimal air temperature of 45 ± 1 °C as dependent upon PAR (photosynthetically active radiation) intensity and the duration of the exposure to the stress factor. Chufa plants were grown hydroponically, on expanded clay, under artificial light. The nutrient solution was Knop's mineral medium. Until the plants were 30 days old, they had been grown at 690 μmol m-2 s-1 PAR and air temperature 25 °C. Thirty-day-old plants were exposed to the temperature 45 °C for 6 h, 20 h, and 44 h at PAR intensities 690 μmol m-2 s-1 and 1150 μmol m-2 s-1. The exposure to the damaging air temperature for 44 h at 690 μmol m-2 s-1 PAR caused irreversible damage to PSA, resulting in leaf mortality. In chufa plants exposed to heat shock treatment at 690 μmol m-2 s-1 PAR for 6 h and 20 h, respiration exceeded photosynthesis, and CO2 release in the light was recorded. Functional activity of photosynthetic apparatus, estimated from parameters of pulse-modulated chlorophyll fluorescence in Photosystem 2 (PS 2), decreased 40% to 50%. After the exposure to the stress factor was finished, functional activity of PSA recovered its initial values, and apparent photosynthesis (Papparent) rate after a 20-h exposure to the stress factor was 2.6 times lower than before the elevation of the temperature. During the first hours of plant exposure to the temperature 45 °C at 1150 μmol m-2 s-1 PAR, respiration rate was higher than photosynthesis rate, but after 3-4 h of the exposure, photosynthetic processes exceeded oxidative ones and CO2 absorption in the light was recorded. At the end of the 6-h exposure, Papparent rate was close to that recorded prior to the exposure, and no significant changes were observed in the functional activity of PSA. At the end of the 20-h exposure, Papparent rate was close to its initial value, but certain parameters of the functional activity of PSA decreased 25% vs. their initial values. During the repair period, the parameters of external gas exchange recovered their initial values, and parameters of pulse-modulated chlorophyll fluorescence were 20-30% higher than their initial values. Thus, exposure of chufa plants to the damaging temperature of the air for 20 h did not cause any irreversible damage to the photosynthetic apparatus of plants at either 690 μmol m-2 s-1 or 1150 μmol m-2 s-1 PAR, and higher PAR intensity during the heat shock treatment enhanced heat tolerance of the plants.

Guiding of High Laser Intensities in Long Plasma Channels

NASA Astrophysics Data System (ADS)

Levin, M.; Eisenmann, S.; Palchan, T.; Zigler, A.; Sugiyama, K.; Nakajima, K.; Kaganovich, D.; Hubbard, R. F.; Ting, A.; Gordon, D. F.; Sprangle, P.; Fraenkel, M.; Maman, S.; Henis, Z.

Plasma channels have been widely used to guide intense laser pulses over many Rayleigh lengths. Using optimized segmented capillary discharges, we demonstrated guided propagation of ultra short (100 fs) high intensity (1016 W/cm-2, limited by the laser system) pulses over distances up to 12.6 cm and intensities above 1018W/cm2 for 1.5cm boron nitride capillary. Both radial and longitudinal density profiles of plasma channels were studied under various discharge conditions. A new diagnostic technique is presented in which the transport of a guided laser pulse at different delay times from the initiation of the discharge is sampled on a single discharge shot. Using external, 10 nsec Nd YAG laser of several tenths of milijoules to ignite polyethylene capillaries we have demonstrated channels of various length in density range of 1017 - 1019 cm-3 and up to 25% deep. The longitudinal profiles were found to be remarkably uniform in both short and long capillaries. The Boron Nitride capillary has provided a guiding medium that can withstand more than 1000 shots. Using these capillaries we have guided laser intensities above 1018W/cm2. The laser ignition of capillary discharge provided reliable almost jitter free approach. The concerns related to influence of relatively high current density flow through capillary on the injected electrons were studied extensively by us both theoretically and experimentally using a simple injection method. The method is based on the interaction of a high intensity laser pulse with a thin wire placed near capillary entrance. The influence of magnetic fields was found to be insignificant. Using this method we have studied transport of electrons though capillary discharge.

Nigral stimulation for resistant axial motor impairment in Parkinson’s disease? A randomized controlled trial

PubMed Central

Walach, Margarete; Meisner, Christoph; Fritz, Melanie; Scholten, Marlieke; Breit, Sorin; Plewnia, Christian; Bender, Benjamin; Gharabaghi, Alireza; Wächter, Tobias

2013-01-01

Gait and balance disturbances typically emerge in advanced Parkinson’s disease with generally limited response to dopaminergic medication and subthalamic nucleus deep brain stimulation. Therefore, advanced programming with interleaved pulses was put forward to introduce concomittant nigral stimulation on caudal contacts of a subthalamic lead. Here, we hypothesized that the combined stimulation of subthalamic nucleus and substantia nigra pars reticulata improves axial symptoms compared with standard subthalamic nucleus stimulation. Twelve patients were enrolled in this 2 × 2 cross-over double-blind randomized controlled clinical trial and both the safety and efficacy of combined subthalamic nucleus and substantia nigra pars reticulata stimulation were evaluated compared with standard subthalamic nucleus stimulation. The primary outcome measure was the change of a broad-scaled cumulative axial Unified Parkinson’s Disease Rating Scale score (Scale II items 13–15, Scale III items 27–31) at ‘3-week follow-up’. Secondary outcome measures specifically addressed freezing of gait, balance, quality of life, non-motor symptoms and neuropsychiatric symptoms. For the primary outcome measure no statistically significant improvement was observed for combined subthalamic nucleus and substantia nigra pars reticulata stimulation at the ‘3-week follow-up’. The secondary endpoints, however, revealed that the combined stimulation of subthalamic nucleus and substantia nigra pars reticulata might specifically improve freezing of gait, whereas balance impairment remained unchanged. The combined stimulation of subthalamic nucleus and substantia nigra pars reticulata was safe, and of note, no clinically relevant neuropsychiatric adverse effect was observed. Patients treated with subthalamic nucleus and substantia nigra pars reticulata stimulation revealed no ‘global’ effect on axial motor domains. However, this study opens the perspective that concomittant stimulation of the substantia nigra pars reticulata possibly improves otherwise resistant freezing of gait and, therefore, highly warrants a subsequent phase III randomized controlled trial. PMID:23757762

Inhibition of Protease-Activated Receptor (PAR1) Reduces Activation of the Endothelium, Coagulation, Fibrinolysis and Inflammation during Human Endotoxemia.

PubMed

Schoergenhofer, Christian; Schwameis, Michael; Gelbenegger, Georg; Buchtele, Nina; Thaler, Barbara; Mussbacher, Marion; Schabbauer, Gernot; Wojta, Johann; Jilma-Stohlawetz, Petra; Jilma, Bernd

2018-06-04

The protease-activated receptor-1 (PAR-1) is critically involved in the co-activation of coagulation and inflammatory responses. Vorapaxar is a reversible, orally active, low molecular weight, competitive antagonist of PAR-1.We investigated the effects of PAR-1 inhibition by vorapaxar on the inflammatory response, the activation of coagulation, fibrinolysis and endothelium during experimental endotoxemia. In this randomized, double blind, crossover trial, 16 healthy volunteers received a bolus infusion of 2 ng/kg lipopolysaccharide (LPS) ± placebo/vorapaxar with a washout period of 8 weeks. Vorapaxar dosing was guided by thrombin receptor-activating peptide-6-induced whole blood aggregometry. Participants received 10 mg vorapaxar or placebo as an initial dose and, depending on the aggregometry, potentially an additional 10 mg. Goal was > 80% inhibition of aggregation compared with baseline. Vorapaxar significantly reduced the LPS-induced increase in pro-thrombin fragments F1 + 2 by a median of 27% (quartiles: 11-49%), thrombin-anti-thrombin concentrations by 22% (-3 to 46%) and plasmin-anti-plasmin levels by 38% (23-53%). PAR-1 inhibition dampened peak concentrations of tumour necrosis factor -α, interleukin-6 and consequently C-reactive protein by 66% (-11-71%), 50% (15-79%) and 23% (16-38%), respectively. Vorapaxar decreased maximum von Willebrand factor levels by 29% (26-51%) and soluble E-selectin concentrations by 30% (25-38%) after LPS infusion. PAR-1 inhibition did not affect thrombomodulin, soluble P-selectin and platelet factor-4 concentrations.PAR-1 inhibition significantly reduced the activation of coagulation, fibrinolysis, the inflammatory response and endothelial activation during experimental human endotoxemia. Schattauer GmbH Stuttgart.

3D Printing Based on Cardiac CT Assists Anatomic Visualization Prior to Transcatheter Aortic Valve Replacement

PubMed Central

Ripley, Beth; Kelil, Tatiana; Cheezum, Michael K.; Goncalves, Alexandra; Di Carli, Marcelo F.; Rybicki, Frank J.; Steigner, Mike; Mitsouras, Dimitrios; Blankstein, Ron

2017-01-01

Background 3D printing is a promising technique that may have applications in medicine, and there is expanding interest in the use of patient-specific 3D models to guide surgical interventions. Objective To determine the feasibility of using cardiac CT to print individual models of the aortic root complex for transcatheter aortic valve replacement (TAVR) planning as well as to determine the ability to predict paravalvular aortic regurgitation (PAR). Methods This retrospective study included 16 patients (9 with PAR identified on blinded interpretation of post-procedure trans-thoracic echocardiography and 7 age, sex, and valve size-matched controls with no PAR). 3D printed models of the aortic root were created from pre-TAVR cardiac computed tomography data. These models were fitted with printed valves and predictions regarding post-implant PAR were made using a light transmission test. Results Aortic root 3D models were highly accurate, with excellent agreement between annulus measurements made on 3D models and those made on corresponding 2D data (mean difference of −0.34 mm, 95% limits of agreement: ± 1.3 mm). The 3D printed valve models were within 0.1 mm of their designed dimensions. Examination of the fit of valves within patient-specific aortic root models correctly predicted PAR in 6 of 9 patients (6 true positive, 3 false negative) and absence of PAR in 5 of 7 patients (5 true negative, 2 false positive). Conclusions Pre-TAVR 3D-printing based on cardiac CT provides a unique patient-specific method to assess the physical interplay of the aortic root and implanted valves. With additional optimization, 3D models may complement traditional techniques used for predicting which patients are more likely to develop PAR. PMID:26732862

Réunion publique HR

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

None

2010-04-30

Chers Collègues,Je me permets de vous rappeler qu'une réunion publique organisée par le Département HR se tiendra aujourd'hui:Vendredi 30 avril 2010 à 9h30 dans l'Amphithéâtre principal (café offert dès 9h00).Durant cette réunion, des informations générales seront données sur:le CERN Admin e-guide, qui est un nouveau guide des procédures administratives du CERN ayant pour but de faciliter la recherche d'informations pratiques et d'offrir un format de lecture convivial;le régime d'Assurance Maladie de l'Organisation (présentation effectuée par Philippe Charpentier, Président du CHIS Board) et;la Caisse de Pensions (présentation effectuée par Théodore Economou, Administrateur de la Caisse de Pensions du CERN).Une transmission simultanéemore » de cette réunion sera assurée dans l'Amphithéâtre BE de Prévessin et également disponible à l'adresse suivante: http://webcast.cern.chJe me réjouis de votre participation!Meilleures salutations,Anne-Sylvie CatherinChef du Département des Ressources humaines__________________________________________________________________________________Dear Colleagues,I should like to remind you that a plublic meeting organised by HR Department will be held today:Friday 30 April 2010 at 9:30 am in the Main Auditorium (coffee from 9:00 am).During this meeting, general information will be given about:the CERN Admin e-guide which is a new guide to the Organization's administrative procedures, drawn up to facilitate the retrieval of practical information and to offer a user-friendly format;the CERN Health Insurance System (presentation by Philippe Charpentier, President of the CHIS Board) and;the Pension Fund (presentation by Theodore Economou, Administrator of the CERN Pension Fund).A simultaneous transmission of this meeting will be broadcast in the BE Auditorium at Prévessin and will also be available at the following address. http://webcast.cern.chI look forward to your participation!Best regards,Anne-Sylvie CatherinHead, Human Resources Department« less

Réunion publique HR

ScienceCinema

None

2017-12-09

Chers Collègues,Je me permets de vous rappeler qu'une réunion publique organisée par le Département HR se tiendra aujourd'hui:Vendredi 30 avril 2010 à 9h30 dans l'Amphithéâtre principal (café offert dès 9h00).Durant cette réunion, des informations générales seront données sur:le CERN Admin e-guide, qui est un nouveau guide des procédures administratives du CERN ayant pour but de faciliter la recherche d'informations pratiques et d'offrir un format de lecture convivial;le régime d'Assurance Maladie de l'Organisation (présentation effectuée par Philippe Charpentier, Président du CHIS Board) et;la Caisse de Pensions (présentation effectuée par Théodore Economou, Administrateur de la Caisse de Pensions du CERN).Une transmission simultanée de cette réunion sera assurée dans l'Amphithéâtre BE de Prévessin et également disponible à l'adresse suivante: http://webcast.cern.chJe me réjouis de votre participation!Meilleures salutations,Anne-Sylvie CatherinChef du Département des Ressources humaines__________________________________________________________________________________Dear Colleagues,I should like to remind you that a plublic meeting organised by HR Department will be held today:Friday 30 April 2010 at 9:30 am in the Main Auditorium (coffee from 9:00 am).During this meeting, general information will be given about:the CERN Admin e-guide which is a new guide to the Organization's administrative procedures, drawn up to facilitate the retrieval of practical information and to offer a user-friendly format;the CERN Health Insurance System (presentation by Philippe Charpentier, President of the CHIS Board) and;the Pension Fund (presentation by Theodore Economou, Administrator of the CERN Pension Fund).A simultaneous transmission of this meeting will be broadcast in the BE Auditorium at Prévessin and will also be available at the following address. http://webcast.cern.chI look forward to your participation!Best regards,Anne-Sylvie CatherinHead, Human Resources Department

Coherent population trapping with a controlled dissipation: applications in optical metrology

NASA Astrophysics Data System (ADS)

Nicolas, L.; Delord, T.; Jamonneau, P.; Coto, R.; Maze, J.; Jacques, V.; Hétet, G.

2018-03-01

We analyze the properties of a pulsed coherent population trapping protocol that uses a controlled decay from the excited state in a Λ-level scheme. We study this problem analytically and numerically and find regimes where narrow transmission, absorption, or fluorescence spectral lines occur. We then look for optimal frequency measurements using these spectral features by computing the Allan deviation in the presence of ground state decoherence and show that the protocol is on a par with Ramsey-CPT. We discuss possible implementations with ensembles of alkali atoms and single ions and demonstrate that typical pulsed-CPT experiments that are realized on femto-second timescales can be implemented on micro-seconds timescales using this scheme.

Brain stimulation over Broca’s area differentially modulates naming skills in neurotypical adults and individuals with Asperger’s syndrome

PubMed Central

Fecteau, Shirley; Agosta, Sara; Oberman, Lindsay; Pascual-Leone, Alvaro

2012-01-01

In the present study we tested the hypothesis that, in subjects with Asperger’s syndrome (ASP), the dynamics of language-related regions might be abnormal, so that repetitive transcranial magnetic stimulation (rTMS) over Broca’s area leads to differential behavioral effects as seen in neurotypical controls. We conducted a five-stimulation-site, double-blind, multiple crossover, pseudo-randomized, sham-controlled study in 10 individuals with ASP and 10 age- and gender-matched healthy subjects. Object naming was assessed before and after low-frequency rTMS of the left pars opercularis, left pars triangularis, right pars opercularis and right pars triangularis, and sham stimulation, as guided stereotaxically by each individual’s brain magnetic resonance imaging. In ASP participants, naming improved after rTMS of the left pars triangularis as compared with sham stimulation, whereas rTMS of the adjacent left opercularis lengthened naming latency. In healthy subjects, stimulation of parts of Broca’s area did not lead to significant changes in naming skills, consistent with published data. Overall, these findings support our hypothesis of abnormal language neural network dynamics in individuals with ASP. From a methodological point of view, this work illustrates the use of rTMS to study the dynamics of brain–behavior relations by revealing the differential behavioral impact of non-invasive brain stimulation in a neuropsychiatric disorder. PMID:21676037

Electrical characteristics of thin Ta2O5 films deposited by reactive pulsed direct-current magnetron sputtering

NASA Astrophysics Data System (ADS)

Kim, J.-Y.; Nielsen, M. C.; Rymaszewski, E. J.; Lu, T.-M.

2000-02-01

Room temperature deposition of tantalum oxide films on metallized silicon substrates was investigated by reactive pulsed magnetron sputtering of Ta in an Ar/O2 ambient. The dielectric constant of the tantalum oxide ranged from 19 to 31 depending on the oxygen percentage [P(%)=PO2/(PO2+PAr)] used during sputtering. The leakage current density was less than 10 nA/cm2 at 0.5 MV/cm electric field and the dielectric breakdown field was greater than 3.8 MV/cm for P=60%. A charge storage as high as 3.3 μF/cm2 was achieved for 70-Å-thick film. Pulse frequency variation (from 20 to 200 kHz) did not give a significant effect in the electrical properties (dielectric constant or leakage current density) of the Ta2O5 films.

Ultra short laser pulse modification of wave guides

NASA Astrophysics Data System (ADS)

Rosenfeld, Arkadi; Ashkenasi, David

2003-11-01

The high peak powers of ultra short (ps and sub-ps) pulsed lasers available at relatively low single pulse energies potentially allow for a precise localization of photon energy, either on the surface or inside (transparent) materials. Three dimensional micro structuring of bulk transparent media without any sign of mechanical cracking has shown the potential of ultra short laser processing. In this study, the micro structuring of bulk transparent media was used to modify fused silica and especially the cladding-core interface in normal fused silica wave guides. The idea behind this technique is to enforce a local mismatch for total reflection at the interface at minimal mechanic stress to overcome the barrier for enhanced optical out-coupling. The laser-induced modifications were studied in dependence of pulse width, focal alignment, single pulse energy and pulse overlap. Micro traces with a thickness between 3 and 8 μm were generated with a spacing of 10 μm in the subsurface region using sub-ps and ps laser pulses at a wavelength of 800 nm. The optical leakage enforced by a micro spiral pattern is significant and can be utilized for medical applications or potentially also for telecommunications and fiber laser technology.

Ultrashort laser pulse processing of wave guides for medical applications

NASA Astrophysics Data System (ADS)

Ashkenasi, David; Rosenfeld, Arkadi; Spaniol, Stefan B.; Terenji, Albert

2003-06-01

The availability of ultra short (ps and sub-ps) pulsed lasers has stimulated a growing interest in exploiting the enhanced flexibility of femtosecond and/or picosecond laser technology for micro-machining. The high peak powers available at relatively low single pulse energies potentially allow for a precise localization of photon energy, either on the surface or inside (transparent) materials. Three dimensional micro structuring of bulk transparent media without any sign of mechanical cracking has been demonstrated. In this study, the potential of ultra short laser processing was used to modify the cladding-core interface in normal fused silica wave guides. The idea behind this technique is to enforce a local mismatch for total reflection at the interface at minimal mechanic stress. The laser-induced modifications were studied in dependence of pulse width, focal alignment, single pulse energy and pulse overlap. Micro traces with a thickness between 3 and 8 μm were generated with a spacing of 10 μm in the sub-surface region using sub-ps and ps laser pulses at a wavelength of 800 nm. The optical leakage enforced by a micro spiral pattern is significant and can be utilized for medical applications or potentially also for telecommunications and fiber laser technology.

Guiding supersonic projectiles using optically generated air density channels

NASA Astrophysics Data System (ADS)

Johnson, Luke A.; Sprangle, Phillip

2015-09-01

We investigate the feasibility of using optically generated channels of reduced air density to provide trajectory correction (guiding) for a supersonic projectile. It is shown that the projectile experiences a force perpendicular to its direction of motion as one side of the projectile passes through a channel of reduced air density. A single channel of reduced air density can be generated by the energy deposited from filamentation of an intense laser pulse. We propose changing the laser pulse energy from shot-to-shot to build longer effective channels. Current femtosecond laser systems with multi-millijoule pulses could provide trajectory correction of several meters on 5 km trajectories for sub-kilogram projectiles traveling at Mach 3.

Pulsed-light imaging for fluorescence guided surgery under normal room lighting.

PubMed

Sexton, Kristian; Davis, Scott C; McClatchy, David; Valdes, Pablo A; Kanick, Stephen C; Paulsen, Keith D; Roberts, David W; Pogue, Brian W

2013-09-01

Fluorescence guided surgery (FGS) is an emerging technology that has demonstrated improved surgical outcomes. However, dim lighting conditions required by current FGS systems are disruptive to standard surgical workflow. We present a novel FGS system capable of imaging fluorescence under normal room light by using pulsed excitation and gated acquisition. Images from tissue-simulating phantoms confirm visual detection down to 0.25 μM of protoporphyrin IX under 125 μW/cm2 of ambient light, more than an order of magnitude lower than that measured with the Zeiss Pentero in the dark. Resection of orthotopic brain tumors in mice also suggests that the pulsed-light system provides superior sensitivity in vivo.

Pulsed-light imaging for fluorescence guided surgery under normal room lighting

PubMed Central

Sexton, Kristian; Davis, Scott C.; McClatchy, David; Valdes, Pablo A.; Kanick, Stephen C.; Paulsen, Keith D.; Roberts, David W.; Pogue, Brian W.

2013-01-01

Fluorescence guided surgery (FGS) is an emerging technology that has demonstrated improved surgical outcomes. However, dim lighting conditions required bycurrent FGS systems are disruptive to standard surgical workflow. We present a novel FGS system capable of imaging fluorescence under normal room lightby using pulsed excitation and gated acquisition. Images from tissue-simulating phantoms confirm visual detection down to 0.25 μM of protopor-phyrin IX under 125 μW/cm2 of ambient light, more than an order of magnitude lower than that measured with the Zeiss Pentero in the dark. Resection of orthotopic brain tumors in mice also suggests that the pulsed-light system provides superior sensitivity in vivo. PMID:23988926

Phased-array laser radar: Concept and application

NASA Technical Reports Server (NTRS)

Kadrmas, K. A.

1973-01-01

The design and construction of a coaxial transmitter-receiver combination was investigated. Major emphasis was placed on simple permanent optical alignment, transmitter-receiver field of view matching, use of a pulsed gas laser as a transmitter maximum optical efficiency, complete digital control of data acquisition, and optical mount pointing and tracking. Also a means of expanding the coaxial transmitter-receiver concept to allow phased-array lidar, par-lidar was described.

Interactive Effect of UVR and Phosphorus on the Coastal Phytoplankton Community of the Western Mediterranean Sea: Unravelling Eco-Physiological Mechanisms.

PubMed

Carrillo, Presentación; Medina-Sánchez, Juan M; Herrera, Guillermo; Durán, Cristina; Segovia, María; Cortés, Dolores; Salles, Soluna; Korbee, Nathalie; Figueroa, Félix L; Mercado, Jesús M

2015-01-01

Some of the most important effects of global change on coastal marine systems include increasing nutrient inputs and higher levels of ultraviolet radiation (UVR, 280-400 nm), which could affect primary producers, a key trophic link to the functioning of marine food webs. However, interactive effects of both factors on the phytoplankton community have not been assessed for the Mediterranean Sea. An in situ factorial experiment, with two levels of ultraviolet solar radiation (UVR+PAR vs. PAR) and nutrients (control vs. P-enriched), was performed to evaluate single and UVR×P effects on metabolic, enzymatic, stoichiometric and structural phytoplanktonic variables. While most phytoplankton variables were not affected by UVR, dissolved phosphatase (APAEX) and algal P content increased in the presence of UVR, which was interpreted as an acclimation mechanism of algae to oligotrophic marine waters. Synergistic UVR×P interactive effects were positive on photosynthetic variables (i.e., maximal electron transport rate, ETRmax), but negative on primary production and phytoplankton biomass because the pulse of P unmasked the inhibitory effect of UVR. This unmasking effect might be related to greater photodamage caused by an excess of electron flux after a P pulse (higher ETRmax) without an efficient release of carbon as the mechanism to dissipate the reducing power of photosynthetic electron transport.

Reestablishing Clinical Psychology's Subjective Core

ERIC Educational Resources Information Center

Hunsberger, Peter Hume

2007-01-01

Comments on the report by the APA Presidential Task Force on Evidence-Based Practice (see record 2006-05893-001) entitled Evidence-based practice in psychology. The Task Force is to be commended for their report valuing evidence from "clinical expertise" on a par with "research data" (p. 272) in guiding psychological practices. The current author…

MR-Guided Pulsed High-Intensity Focused Ultrasound Enhancement of Gene Therapy Combined With Androgen Deprivation and Radiotherapy for Prostate Cancer Treatment

DTIC Science & Technology

2009-09-01

first statement of work is to determine if high intensity focused ultrasound ( HIFU ) increases the cellular uptake of AS-MDM2, AS-bcl-2 and AS-PKA...Drug Delivery in Prostate Tumor in vivo Using MR Guided Focused Ultrasound (MRg HIFU ). WC, IFMBE Proceedings 25: pp341-344, 2009 6...pharmaceutical agents in the treatment target. In the model system proposed, pulsed high intensity focused ultrasound ( HIFU ) is hypothesized to improve

High accuracy electronic material level sensor

DOEpatents

McEwan, T.E.

1997-03-11

The High Accuracy Electronic Material Level Sensor (electronic dipstick) is a sensor based on time domain reflectometry (TDR) of very short electrical pulses. Pulses are propagated along a transmission line or guide wire that is partially immersed in the material being measured; a launcher plate is positioned at the beginning of the guide wire. Reflected pulses are produced at the material interface due to the change in dielectric constant. The time difference of the reflections at the launcher plate and at the material interface are used to determine the material level. Improved performance is obtained by the incorporation of: (1) a high accuracy time base that is referenced to a quartz crystal, (2) an ultrawideband directional sampler to allow operation without an interconnect cable between the electronics module and the guide wire, (3) constant fraction discriminators (CFDs) that allow accurate measurements regardless of material dielectric constants, and reduce or eliminate errors induced by triple-transit or ``ghost`` reflections on the interconnect cable. These improvements make the dipstick accurate to better than 0.1%. 4 figs.

High accuracy electronic material level sensor

DOEpatents

McEwan, Thomas E.

1997-01-01

The High Accuracy Electronic Material Level Sensor (electronic dipstick) is a sensor based on time domain reflectometry (TDR) of very short electrical pulses. Pulses are propagated along a transmission line or guide wire that is partially immersed in the material being measured; a launcher plate is positioned at the beginning of the guide wire. Reflected pulses are produced at the material interface due to the change in dielectric constant. The time difference of the reflections at the launcher plate and at the material interface are used to determine the material level. Improved performance is obtained by the incorporation of: 1) a high accuracy time base that is referenced to a quartz crystal, 2) an ultrawideband directional sampler to allow operation without an interconnect cable between the electronics module and the guide wire, 3) constant fraction discriminators (CFDs) that allow accurate measurements regardless of material dielectric constants, and reduce or eliminate errors induced by triple-transit or "ghost" reflections on the interconnect cable. These improvements make the dipstick accurate to better than 0.1%.

Stabilisation de l'etat de polarisation d'un laser par la conception et fabrication d'un miroir polarisant fait de couches minces nanostructurees

NASA Astrophysics Data System (ADS)

Doucet, Alexandre

Ce manuscrit presente la conception et la fabrication d'un miroir polarisant fabrique avec la methode de deposition par incidence oblique communement appelee en anglais GLAD (GLancing Angle Deposition). Cette methode de deposition par GLAD permet de changer la nanostructure des revetements avec l'inclinaison et la rotation du substrat par rapport au flux de materiau evapore. Ceci nous permet d'ajuster l'indice de refraction et d'obtenir des revetements birefringents avec un materiau intrinsequement isotrope. Puisque l'indice de refraction peut etre change, les miroirs sont fabriques avec un seul materiau contrairement aux methodes usuelles qui necessite deux materiaux. Les proprietes optiques des echantillons sont mesurees avec l'aide de l'ellipsometrie. Des images avec un microscope electronique a balayage par transmission permettent de verifier Ia structure des revetements deposes. Les miroirs sont utilises comme coupleurs de sortie du resonateur d'un laser avec un milieu actif d'(Yb3+0.1 Y 0.9)3Al5O12, ou plus simplement Yb: YAG, pompe optiquement avec une diode laser. Ces cristaux presentent des proprietes optiques interessantes pour leur utilisation comme milieu actif, mais avec une structure cristalline cubique, ils donnent lieu a des faisceaux polarises aleatoirement. Les miroirs que nous fabriquons permettent d'obtenir une emission polarisee lineairement sans avoir a ajouter d'autres elements au resonateur. Les tests sont faits en regime continu et pulse avec un absorbant saturable de Cr : Y AG. Deux materiaux sont etudies, soit le WO3 et le TiO2, et ils nous permettent d'obtenir une emission polarisee lineairement dans le mode TEM 00 avec un rapport d'extinction de 1000 (30 dB), mais seuls les miroirs de TiO2 permettent une emission pulsee periodique avec une densite de puissance crete pres de 700+/-80 MW/cm2. En etudiant le rapport d'extinction en fonction du temps de pompage, nous remarquons que l'etat de polarisation est beaucoup plus stable que celui obtenu avec un miroir isotrope. Des mesures du spectre d'emission avec un spectrometre de haute resolution permettent de constater le caractere multimode longitudinal en regime continu et une emission monomode longitudinale en regime pulse. None None None None None None None None None None None None None None None None None None None None None None None

Design of pulsed guiding magnetic field for high power microwave generators.

PubMed

Ju, J-C; Zhang, H; Zhang, J; Shu, T; Zhong, H-H

2014-09-01

In this paper, we present a comprehensive study on designing solenoid together with the corresponding power supply system to excite pulsed magnetic field required for high power microwave generators. Particularly, a solenoid is designed and the excited magnetic field is applied to a Ku-band overmoded Cerenkov generator. It is found in experiment that the electron beam is properly guided by the magnetic field and a 1.1 GW high power microwave is achieved at a central frequency of 13.76 GHz. Pulsed solenoid system has the advantages of compactness and low energy consumption, which are of great interest for repetitive operation. The reported studies and results can be generalized to other applications which require magnetic fields.

Coupling of laser energy into plasma channels

NASA Astrophysics Data System (ADS)

Dimitrov, D. A.; Giacone, R. E.; Bruhwiler, D. L.; Busby, R.; Cary, J. R.; Geddes, C. G. R.; Esarey, E.; Leemans, W. P.

2007-04-01

Diffractive spreading of a laser pulse imposes severe limitations on the acceleration length and maximum electron energy in the laser wake field accelerator (LWFA). Optical guiding of a laser pulse via plasma channels can extend the laser-plasma interaction distance over many Rayleigh lengths. Energy efficient coupling of laser pulses into and through plasma channels is very important for optimal LWFA performance. Results from simulation parameter studies on channel guiding using the particle-in-cell (PIC) code VORPAL [C. Nieter and J. R. Cary, J. Comput. Phys. 196, 448 (2004)] are presented and discussed. The effects that density ramp length and the position of the laser pulse focus have on coupling into channels are considered. Moreover, the effect of laser energy leakage out of the channel domain and the effects of tunneling ionization of a neutral gas on the guided laser pulse are also investigated. Power spectral diagnostics were developed and used to separate pump depletion from energy leakage. The results of these simulations show that increasing the density ramp length decreases the efficiency of coupling a laser pulse to a channel and increases the energy loss when the pulse is vacuum focused at the channel entrance. Then, large spot size oscillations result in increased energy leakage. To further analyze the coupling, a differential equation is derived for the laser spot size evolution in the plasma density ramp and channel profiles are simulated. From the numerical solution of this equation, the optimal spot size and location for coupling into a plasma channel with a density ramp are determined. This result is confirmed by the PIC simulations. They show that specifying a vacuum focus location of the pulse in front of the top of the density ramp leads to an actual focus at the top of the ramp due to plasma focusing, resulting in reduced spot size oscillations. In this case, the leakage is significantly reduced and is negligibly affected by ramp length, allowing for efficient use of channels with long ramps.

Number and brightness image analysis reveals ATF-induced dimerization kinetics of uPAR in the cell membrane

PubMed Central

Hellriegel, Christian; Caiolfa, Valeria R.; Corti, Valeria; Sidenius, Nicolai; Zamai, Moreno

2011-01-01

We studied the molecular forms of the GPI-anchored urokinase plasminogen activator receptor (uPAR-mEGFP) in the human embryo kidney (HEK293) cell membrane and demonstrated that the binding of the amino-terminal fragment (ATF) of urokinase plasminogen activator is sufficient to induce the dimerization of the receptor. We followed the association kinetics and determined precisely the dimeric stoichiometry of uPAR-mEGFP complexes by applying number and brightness (N&B) image analysis. N&B is a novel fluctuation-based approach for measuring the molecular brightness of fluorophores in an image time sequence in live cells. Because N&B is very sensitive to long-term temporal fluctuations and photobleaching, we have introduced a filtering protocol that corrects for these important sources of error. Critical experimental parameters in N&B analysis are illustrated and analyzed by simulation studies. Control experiments are based on mEGFP-GPI, mEGFP-mEGFP-GPI, and mCherry-GPI, expressed in HEK293. This work provides a first direct demonstration of the dimerization of uPAR in live cells. We also provide the first methodological guide on N&B to discern minor changes in molecular composition such as those due to dimerization events, which are involved in fundamental cell signaling mechanisms.—Hellriegel, C., Caiolfa, V. R., Corti, V., Sidenius, N., Zamai, M. Number and brightness image analysis reveals ATF-induced dimerization kinetics of uPAR in the cell membrane. PMID:21602447

Faraday spectroscopy of ultracold atoms guided in hollow core optical fibers

NASA Astrophysics Data System (ADS)

Fatemi, Fredrik; Pechkis, Joseph

2013-05-01

We have performed spatially and temporally resolved magnetometry using Faraday spectroscopy of ultracold rubidium atoms confined in hollow core optical fibers. We first guide 105 Rb atoms into a 3-cm-long, 100-micron-core hollow fiber using blue-detuned hollow waveguide modes. Inside the fiber, the atoms are exposed to an optical pumping pulse, and the Larmor precession is monitored by the polarization rotation of a probe laser beam detuned by 50 GHz. The intense guide beams can perturb the detected Larmor precession frequencies, but we show that by confining the atoms to the intensity null of higher order blue-detuned hollow modes, these perturbations are reduced by over 95% compared to red-detuned guides. By adjusting the guide beam detuning and polarization, the deleterious effects of both photon scattering and frequency shifts can be suppressed such that multiple magnetic field measurements with sensitivity of 30 nT per sampling pulse can be obtained throughout the length of the fiber in a single loading cycle. Work supported by ONR and DARPA.

From Person-in-Environment to Strengths: The Promise of Postmodern Practice

ERIC Educational Resources Information Center

Dybicz, Phillip

2015-01-01

Social work relies heavily on its value base to guide practice; however, there are no conceptual models--on par with person-in-environment (PIE)--to describe how these values are implemented within an evidence-based approach. However, the philosophical foundation of empiricism and positivism that lends PIE its strength also brings with it inherent…

Laser-induced breakdown spectroscopy measurement of a small fraction of rhenium in bulk tungsten

NASA Astrophysics Data System (ADS)

Nishijima, D.; Ueda, Y.; Doerner, R. P.; Baldwin, M. J.; Ibano, K.

2018-03-01

Laser-induced breakdown spectroscopy (LIBS) of bulk rhenium (Re) and tungsten (W)-Re alloy has been performed using a Q-switched Nd:YAG laser (wavelength = 1064 nm, pulse width ∼4-6 ns, laser energy = 115 mJ). It is found that the electron temperature, Te, of laser-induced Re plasma is lower than that of W plasma, and that Te of W-Re plasma is in between Re and W plasmas. This indicates that material properties affect Te in a laser-induced plasma. For analysis of W-3.3%Re alloy, only the strongest visible Re I 488.9 nm line is found to be used because of the strong enough intensity without contamination with W lines. Using the calibration-free LIBS method, the atomic fraction of Re, cRe, is evaluated as a function of the ambient Ar gas pressure, PAr. At PAr < 10 Torr, LIBS-measured cRe agrees well with that from EDX (energy-dispersive X-ray micro-analysis), while cRe increases with an increase in PAr at >10 Torr due to spectral overlapping of the Re I 488.9 nm line by an Ar II 488.9 nm line.

Pulse cleaning flow models and numerical computation of candle ceramic filters.

PubMed

Tian, Gui-shan; Ma, Zhen-ji; Zhang, Xin-yi; Xu, Ting-xiang

2002-04-01

Analytical and numerical computed models are developed for reverse pulse cleaning system of candle ceramic filters. A standard turbulent model is demonstrated suitably to the designing computation of reverse pulse cleaning system from the experimental and one-dimensional computational result. The computed results can be used to guide the designing of reverse pulse cleaning system, which is optimum Venturi geometry. From the computed results, the general conclusions and the designing methods are obtained.

Demonstration of uneven distribution of intracranial pulsatility in hydrocephalus patients.

PubMed

Eide, Per K

2008-11-01

Data from intracranial pressure (ICP) recordings in patients with hydrocephalus were reviewed to determine whether intracranial pulsatility within the cerebrospinal fluid (CSF) of cerebral ventricles (ICP(LV)) may differ from that within the brain parenchyma (ICP(PAR)), and whether pulsatility may differ between noncommunicating ventricles. The authors retrieved data from recordings previously obtained in 7 patients with hydrocephalus (noncommunicating in 4 and communicating in 3) and shunt failure who received both an external ventricular drainage (EVD) and an ICP sensor as part of surveillance during intensive care. Simultaneous ICP(LV) and ICP(PAR) signals were available in 6 cases, and simultaneous signals from the lateral and fourth ventricles (ICP(LV) and ICP4V, respectively) were recorded in 1 case. The recordings with both signals were parsed into 6-second time windows. Pulsatility was characterized by the wave amplitude and rise time coefficient, and differences in pulsatility between the ICP(LV) and ICP(PAR) signals (6 cases) or ICP(LV) and ICP4V signals (1 case) were determined. There was uneven distribution of intracranial pulsatility in all 7 patients, shown as significantly elevated pulsatility (that is, higher wave amplitudes and rise time coefficients) within the ventricles (ICP(LV)) than within brain parenchyma (ICP(PAR)) in 6 patients, and significantly higher pulsatility in the fourth (ICP4V) than in the lateral (ICP(LV)) ventricles in 1 patient. Differences > or = 1 mm Hg in ICP wave amplitude were found in 0.5-100% (median 9.4%) of observations in the 7 patients (total number of 6-second time windows, 68,242). The present observations demonstrate uneven distribution of intracranial pulsatility in patients with hydrocephalus, higher pulse pressure amplitudes within the ventricular CSF (ICP(LV)) than within the brain parenchyma (ICP(PAR)). This may be one mechanism behind ventricular enlargement in hydrocephalus.

PAR and UV effects on vertical migration and photosynthesis in Euglena gracilis.

PubMed

Richter, Peter; Helbling, Walter; Streb, Christine; Häder, Donat-P

2007-01-01

Recently it was shown that the unicellular flagellate Euglena gracilis changes the sign of gravitaxis from negative to positive upon excessive radiation. This sign change persists in a cell culture for hours even if subsequently transferred to dim light. To test the ecological relevance of this behavior, a vertical column experiment was performed (max. depth 65 cm) to test distribution, photosynthetic efficiency and motility in different horizons of the column (surface, 20, 40 and 65 cm). One column was covered with a UV cut-off filter, which transmits photosynthetically active radiation (PAR) only, the other with a filter which transmits PAR and UV. The columns were irradiated with a solar simulator (PAR 162 W m(-2), UV-A 32.6 W m(-2), UV-B 1.9 W m(-2)). The experiment was conducted for 10 days, normally with a light/dim light cycle of 12 h:12 h, but in some cases the light regime was changed (dim light instead of full radiation). Under irradiation the largest fraction of cells was found at the bottom of the column. The cell density decreased toward the surface. Photosynthetic efficiency, determined with a pulse amplitude modulated fluorometer, was negligible at the surface and increased toward the bottom. While the cell suspension showed a positive gravitaxis at the bottom, the cells in the 40 cm horizon were bimodally oriented (about the same percentage of cells swimming upward and downward, respectively). At 20 cm and at the surface the cells showed negative gravitaxis. Positive gravitaxis was more pronounced in the UV + PAR samples. At the surface and in the 20 and 40 cm horizons photosynthetic efficiency was better in the PAR-only samples than in the PAR + UV samples. At the bottom photosynthetic efficiency was similar in both light treatments. The data suggest that high light reverses gravitaxis of the cells, so that they move downward in the water column. At the bottom the light intensity is lower (attenuation of the water column and self shading of the cells) and the cells recover. After recovery the cells swim upward again until the negative gravitaxis is reversed again.

INTERNATIONAL CONFERENCE ON SEMICONDUCTOR INJECTION LASERS SELCO-87: Behavior of gain-guided lasers generating high-power nanosecond pulses

NASA Astrophysics Data System (ADS)

Erbert, G.

1988-11-01

Computer-controlled apparatus was used in an investigation of gain-guided narrow-stripe AlGaAs double heterostructure lasers. These lasers were excited with current pulses of 10 ns duration and amplitudes up to 3 A. The watt-ampere characteristics together with near- and far-field radiation patterns were considered using an analytic model of the lasers. The results showed that the values of the gain under a stripe contact or of the absorption outside this region varied with the output power.

High-Altitude Electromagnetic Pulse (HEMP) Testing

DTIC Science & Technology

2011-11-10

Security Classification Guide ( SCG ). b. The HEMP simulation facility shall have a measured map of the peak amplitude waveform of the...Quadripartite Standardization Agreement s, sec second SCG security classification guide SN serial number SOP Standard Operating Procedure

Enhanced thermal stability of silica-coated gold nanorods for photoacoustic imaging and image-guided therapy.

PubMed

Chen, Yun-Sheng; Frey, Wolfgang; Kim, Seungsoo; Homan, Kimberly; Kruizinga, Pieter; Sokolov, Konstantin; Emelianov, Stanislav

2010-04-26

Photothermal stability and, therefore, consistency of both optical absorption and photoacoustic response of the plasmonic nanoabsorbers is critical for successful photoacoustic image-guided photothermal therapy. In this study, silica-coated gold nanorods were developed as a multifunctional molecular imaging and therapeutic agent suitable for image-guided photothermal therapy. The optical properties and photothermal stability of silica-coated gold nanorods under intense irradiation with nanosecond laser pulses were investigated by UV-Vis spectroscopy and transmission electron microscopy. Silica-coated gold nanorods showed increased photothermal stability and retained their superior optical properties under much higher fluences. The changes in photoacoustic response of PEGylated and silica-coated nanorods under laser pulses of various fluences were compared. The silica-coated gold nanorods provide a stable photoacoustic signal, which implies better imaging capabilities and make silica-coated gold nanorods a promising imaging and therapeutic nano-agent for photoacoustic imaging and image-guided photothermal therapy.

Enhanced thermal stability of silica-coated gold nanorods for photoacoustic imaging and image-guided therapy

PubMed Central

Chen, Yun-Sheng; Frey, Wolfgang; Kim, Seungsoo; Homan, Kimberly; Kruizinga, Pieter; Sokolov, Konstantin; Emelianov, Stanislav

2010-01-01

Photothermal stability and, therefore, consistency of both optical absorption and photoacoustic response of the plasmonic nanoabsorbers is critical for successful photoacoustic image-guided photothermal therapy. In this study, silica-coated gold nanorods were developed as a multifunctional molecular imaging and therapeutic agent suitable for image-guided photothermal therapy. The optical properties and photothermal stability of silica-coated gold nanorods under intense irradiation with nanosecond laser pulses were investigated by UV-Vis spectroscopy and transmission electron microscopy. Silica-coated gold nanorods showed increased photothermal stability and retained their superior optical properties under much higher fluences. The changes in photoacoustic response of PEGylated and silica-coated nanorods under laser pulses of various fluences were compared. The silica-coated gold nanorods provide a stable photoacoustic signal, which implies better imaging capabilities and make silica-coated gold nanorods a promising imaging and therapeutic nano-agent for photoacoustic imaging and image-guided photothermal therapy. PMID:20588732

3D printing based on cardiac CT assists anatomic visualization prior to transcatheter aortic valve replacement.

PubMed

Ripley, Beth; Kelil, Tatiana; Cheezum, Michael K; Goncalves, Alexandra; Di Carli, Marcelo F; Rybicki, Frank J; Steigner, Mike; Mitsouras, Dimitrios; Blankstein, Ron

2016-01-01

3D printing is a promising technique that may have applications in medicine, and there is expanding interest in the use of patient-specific 3D models to guide surgical interventions. To determine the feasibility of using cardiac CT to print individual models of the aortic root complex for transcatheter aortic valve replacement (TAVR) planning as well as to determine the ability to predict paravalvular aortic regurgitation (PAR). This retrospective study included 16 patients (9 with PAR identified on blinded interpretation of post-procedure trans-thoracic echocardiography and 7 age, sex, and valve size-matched controls with no PAR). 3D printed models of the aortic root were created from pre-TAVR cardiac computed tomography data. These models were fitted with printed valves and predictions regarding post-implant PAR were made using a light transmission test. Aortic root 3D models were highly accurate, with excellent agreement between annulus measurements made on 3D models and those made on corresponding 2D data (mean difference of -0.34 mm, 95% limits of agreement: ± 1.3 mm). The 3D printed valve models were within 0.1 mm of their designed dimensions. Examination of the fit of valves within patient-specific aortic root models correctly predicted PAR in 6 of 9 patients (6 true positive, 3 false negative) and absence of PAR in 5 of 7 patients (5 true negative, 2 false positive). Pre-TAVR 3D-printing based on cardiac CT provides a unique patient-specific method to assess the physical interplay of the aortic root and implanted valves. With additional optimization, 3D models may complement traditional techniques used for predicting which patients are more likely to develop PAR. Copyright © 2016 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

Effects of nanomaterial saturable absorption on gain-guide soliton in a positive group-dispersion fiber laser: Simulations and experiments

NASA Astrophysics Data System (ADS)

Du, Tuanjie; Wan, Xiaojiao; Yang, Runhua; Li, Weiwei; Ruan, Qiujun; Chen, Nan; Luo, Zhengqian

2018-01-01

In recent years, several kinds of nanomaterials have been discovered, and successfully used as saturable absorbers (SAs) for passively mode-locked fiber lasers. However, it is found that most of nanomaterials-based SAs cannot stably generate gain-guide solitons in positive group-dispersion fiber lasers, which is urgently expected to fully understand the inherent reasons. In this paper, we numerically and experimentally investigate the effects of nanomaterial saturable absorption (e.g. modulation depth and saturation optical power) on gain-guide soliton in positive group-dispersion Er3+-doped fiber laser (PGD-EDFL). By numerically solving the Ginzburg-Landau equation, the evolutions of both the mode-locked optical spectrum and pulse duration as a function of modulation depth and saturation optical power are analyzed, respectively. In experiment, we firstly prepare five nanomaterial SAs with the similar insertion loss, which have the different modulation depth from 1.80% to 23.36%, and the different saturation optical power from 8.8 to 536 W. We then perform the experimental comparison by incorporating the five SAs in a same PGD-EDFL cavity, respectively. The experimental results are in good agreement with the numerical ones. Our result reveals that: (1) a low modulation depth cannot support the formation of gain-guide soliton, (2) as the modulation depth increases, the spectral bandwidth of gain-guide soliton increases, the pulse duration decreases and the pulse chirp becomes large, (3) the saturation optical power has the weak influences on the gain-guide soliton performances.

Filtering of higher-order laser modes using plasma structures

NASA Astrophysics Data System (ADS)

Djordjevic, Blagoje; Benedetti, Carlo; Schroeder, Carl; Esarey, Eric; Leemans, Wim

2017-10-01

Plasma structures based on leaky channels are proposed to filter higher-order laser mode content. The evolution and propagation of non-Gaussian laser pulses in leaky channels is studied, and it is shown that, for appropriate laser-plasma parameters, the higher-order laser mode content may be removed while the fundamental mode remains well-guided. The behavior of the multi-mode laser pulse is described analytically, including the derivation of the leakage coefficients, and compared to numerical calculations. Gaussian laser pulse propagation, without higher-order mode content, improves guiding in parabolic plasma channels, enabling extended interaction lengths for laser-plasma accelerator applications. This work was supported by the Director, Office of Science, Office of High Energy Physics, of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231.

HV discharge acceleration by sequences of UV laser filaments with visible and near-infrared pulses

NASA Astrophysics Data System (ADS)

Schubert, Elise; Rastegari, Ali; Feng, Chengyong; Mongin, Denis; Kamer, Brian; Kasparian, Jérôme; Wolf, Jean-Pierre; Arissian, Ladan; Diels, Jean-Claude

2017-12-01

We investigate the triggering and guiding of DC high-voltage discharges over a distance of 37 cm by filaments produced by ultraviolet (266 nm) laser pulses of 200 ps duration. The latter reduce the breakdown electric field by half and allow up to 80% discharge probability in an electric field of 920 kV m–1. This high efficiency is not further increased by adding nanosecond pulses in the Joule range at 532 and at 1064 nm. However, the latter statistically increases the guiding length, thereby accelerating the discharge by a factor of 2. This effect is due both to photodetachment and to the heating of the plasma channel, that increases the efficiency of avalanche ionization and reduces electron attachment and recombination.

Interactive Effect of UVR and Phosphorus on the Coastal Phytoplankton Community of the Western Mediterranean Sea: Unravelling Eco-Physiological Mechanisms

PubMed Central

Carrillo, Presentación; Medina-Sánchez, Juan M.; Herrera, Guillermo; Durán, Cristina; Segovia, María; Cortés, Dolores; Salles, Soluna; Korbee, Nathalie; L. Figueroa, Félix; Mercado, Jesús M.

2015-01-01

Some of the most important effects of global change on coastal marine systems include increasing nutrient inputs and higher levels of ultraviolet radiation (UVR, 280–400 nm), which could affect primary producers, a key trophic link to the functioning of marine food webs. However, interactive effects of both factors on the phytoplankton community have not been assessed for the Mediterranean Sea. An in situ factorial experiment, with two levels of ultraviolet solar radiation (UVR+PAR vs. PAR) and nutrients (control vs. P-enriched), was performed to evaluate single and UVR×P effects on metabolic, enzymatic, stoichiometric and structural phytoplanktonic variables. While most phytoplankton variables were not affected by UVR, dissolved phosphatase (APAEX) and algal P content increased in the presence of UVR, which was interpreted as an acclimation mechanism of algae to oligotrophic marine waters. Synergistic UVR×P interactive effects were positive on photosynthetic variables (i.e., maximal electron transport rate, ETRmax), but negative on primary production and phytoplankton biomass because the pulse of P unmasked the inhibitory effect of UVR. This unmasking effect might be related to greater photodamage caused by an excess of electron flux after a P pulse (higher ETRmax) without an efficient release of carbon as the mechanism to dissipate the reducing power of photosynthetic electron transport. PMID:26599583

PPM-based System for Guided Waves Communication Through Corrosion Resistant Multi-wire Cables

NASA Astrophysics Data System (ADS)

Trane, G.; Mijarez, R.; Guevara, R.; Pascacio, D.

Novel wireless communication channels are a necessity in applications surrounded by harsh environments, for instance down-hole oil reservoirs. Traditional radio frequency (RF) communication schemes are not capable of transmitting signals through metal enclosures surrounded by corrosive gases and liquids. As an alternative to RF, a pulse position modulation (PPM) guided waves communication system has been developed and evaluated using a corrosion resistant 4H18 multi-wire cable, commonly used to descend electronic gauges in down-hole oil applications, as the communication medium. The system consists of a transmitter and a receiver that utilizes a PZT crystal, for electrical/mechanical coupling, attached to each extreme of the multi-wire cable. The modulator is based on a microcontroller, which transmits60 kHz guided wave pulses, and the demodulator is based on a commercial digital signal processor (DSP) module that performs real time DSP algorithms. Experimental results are presented, which were obtained using a 1m corrosion resistant 4H18multi-wire cable, commonly used with downhole electronic gauges in the oil sector. Although there was significant dispersion and multiple mode excitations of the transmitted guided wave energy pulses, the results show that data rates on the order of 500 bits per second are readily available employing PPM and simple communications techniques.

Charting the Functional Relevance of Broca's Area for Visual Word Recognition and Picture Naming in Dutch Using fMRI-Guided TMS

ERIC Educational Resources Information Center

Wheat, Katherine L.; Cornelissen, Piers L.; Sack, Alexander T.; Schuhmann, Teresa; Goebel, Rainer; Blomert, Leo

2013-01-01

Magnetoencephalography (MEG) has shown pseudohomophone priming effects at Broca's area (specifically pars opercularis of left inferior frontal gyrus and precentral gyrus; LIFGpo/PCG) within [approximately]100 ms of viewing a word. This is consistent with Broca's area involvement in fast phonological access during visual word recognition. Here we…

Designing an ultrafast laser virtual laboratory using MATLAB GUIDE

NASA Astrophysics Data System (ADS)

Cambronero-López, F.; Gómez-Varela, A. I.; Bao-Varela, C.

2017-05-01

In this work we present a virtual simulator developed using the MATLAB GUIDE environment based on the numerical resolution of the nonlinear Schrödinger equation (NLS) and using the split step method for the study of the spatial-temporal propagation of nonlinear ultrashort laser pulses. This allows us to study the spatial-temporal propagation of ultrafast pulses as well as the influence of high-order spectral phases such as group delay dispersion and third-order dispersion on pulse compression in time. The NLS can describe several nonlinear effects, in particular in this paper we consider the Kerr effect, cross-polarized wave generation and cubic-quintic propagation in order to highlight the potential of this equation combined with the GUIDE environment. Graphical user interfaces are commonly used in science and engineering teaching due to their educational value, and have proven to be an effective way to engage and motivate students. Specifically, the interactive graphical interfaces presented provide the visualization of some of the most important nonlinear optics phenomena and allows users to vary the values of the main parameters involved.

Effet de la composition des materiaux composites sur la caracterisation et detection par ondes de Lamb

NASA Astrophysics Data System (ADS)

Ostiguy, Pierre-Claude

Les matériaux composites sont de plus en plus utilisés en aéronautique. Leurs excellentes propriétés mécaniques et leur faible poids leur procurent un avantage certain par rapport aux matériaux métalliques. Ceux-ci étant soumis à diverses conditions de chargement et environnementales, ils sont suceptibles de subir plusieurs types d'endommagements, compromettant leur intégrité. Des méthodes fiables d'inspection sont donc nécessaires pour évaluer leur intégrité. Néanmoins, peu d'approches non destructives, embarquées et efficaces sont présentement utilisées. Ce travail de recherche se penche sur l'étude de l'effet de la composition des matériaux composites sur la détection et la caractérisation par ondes guidées. L'objectif du projet est de développer une approche de caractérisation mécanique embarquée permettant d'améliorer la performance d'une approche d'imagerie par antenne piézoélectriques sur des structures composite et métalliques. La contribution de ce projet est de proposer une approche embarquée de caractérisation mécanique par ultrasons qui ne requiert pas une mesure sur une multitude d'échantillons et qui est non destructive. Ce mémoire par articles est divisé en quatre parties, dont les parties deux A quatre présentant les articles publiés et soumis. La première partie présente l'état des connaissances dans la matière nécessaires à l'acomplissement de ce projet de maîtrise. Les principaux sujets traités portent sur les matériaux composites, propagation d'ondes, la modélisation des ondes guidées, la caractérisation par ondes guidées et la surveillance embarquée des structures. La deuxième partie présente une étude de l'effet des propriétés mécaniques sur la performance de l'algorithme d'imagerie Excitelet. L'étude est faite sur une structure isotrope. Les résultats ont démontré que l'algorithme est sensible à l'exactitude des propriétés mécaniques utilisées dans le modèle. Cette sensibilité a également été explorée afin de développer une méthode embarquée permettant d'évaluer les propriétés mécaniques d'une structure. La troisième partie porte sur une étude plus rigoureuse des performances de la méthode de caractérisation mécanique embarquée. La précision, la répétabilité et la robustesse de la méthode sont validés à l'aide d'un simulateur par FEM. Les propriétés estimées avec l'approche de caractérisation sont à moins de 1% des propriétés utilisées dans le modèle, ce qui rivalise avec l'incertitude des méthodes ASTM. L'analyse expérimentale s'est avérée précise et répétable pour des fréquences sous les 200 kHz, permettant d'estimer les propriétés mécaniques à moins de 1% des propriétés du fournisseur. La quatrième partie a démontrée la capacité de l'approche de caractérisation à identifier les propriétés mécaniques d'une plaques composite orthotrope. Les résultats estimés expérimentalement sont inclus dans les barres d'incertitude des propriétés estimées à l'aide des tests ASTM. Finalement, une simulation FEM a démontré la précision de l'approche avec des propriétés mécaniques à moins de 4 % des propriétés du modèle simulé. Mots-clés : Inspection non destructive, composites, caractérisation mécanique, ultrasons, imagerie, SHM, ondes guidées.

New Pulsed Cold Neutron Beam Line for Fundamental Nuclear Physics at LANSCE.

PubMed

Seo, P-N; Bowman, J D; Gericke, M; Gillis, R C; Greene, G L; Leuschner, M B; Long, J; Mahurin, R; Mitchell, G S; Penttila, S I; Peralta, G; Sharapov, E I; Wilburn, W S

2005-01-01

The NPDGamma collaboration has completed the construction of a pulsed cold neutron beam line on flight path12 at the Los Alamos Neutron Science Center (LANSCE). We describe the new beam line and characteristics of the beam. We report results of the moderator brightness and the guide performance measurements. FP12 has the highest pulsed cold neutron intensity for nuclear physics in the world.

Pressure Studies of Protein Dynamics

DTIC Science & Technology

1989-02-26

infrared flash photolysis system with the monitoring light produced by a Spectra-Physics/ Laser Analytics tunable- diode laser and detected by a liquid...refrigerator. Time range extends from about 100 ms to 100 s. The diode laser current is modulated at 10 kHz and the signal is amplified with a PAR 5101...Photolysis is obtained with a Phase-R D 121OOC dye laser using rhodamine 6G (pulse 4 width 500 ns, 0.3 J). Kinetic spectra are obtained from about 10

Computerized tomography-guided sphenopalatine ganglion pulsed radiofrequency treatment in 16 patients with refractory cluster headaches: Twelve- to 30-month follow-up evaluations.

PubMed

Fang, Luo; Jingjing, Lu; Ying, Shen; Lan, Meng; Tao, Wang; Nan, Ji

2016-02-01

Sphenopalatine ganglion percutaneous radiofrequency thermocoagulation treatment can improve the symptoms of cluster headaches to some extent. However, as an ablation treatment, radiofrequency thermocoagulation treatment also has side effects. To preliminarily evaluate the efficacy and safety of a non-ablative computerized tomography-guided pulsed radiofrequency treatment of sphenopalatine ganglion in patients with refractory cluster headaches. We included and analysed 16 consecutive cluster headache patients who failed to respond to conservative therapy from the Pain Management Center at the Beijing Tiantan Hospital between April 2012 and September 2013 treated with pulsed radiofrequency treatment of sphenopalatine ganglion. Eleven of 13 episodic cluster headaches patients and one of three chronic cluster headaches patient were completely relieved of the headache within an average of 6.3 ± 6.0 days following the treatment. Two episodic cluster headache patients and two chronic cluster headache patients showed no pain relief following the treatment. The mean follow-up time was 17.0 ± 5.5 months. All patients enrolled in this study showed no treatment-related side effects or complications. Our data show that patients with refractory episodic cluster headaches were quickly, effectively and safely relieved from the cluster period after computerized tomography-guided pulsed radiofrequency treatment of sphenopalatine ganglion, suggesting that it may be a therapeutic option if conservative treatments fail. © International Headache Society 2015.

Sex Differences in Cardiovascular and Subjective Stress Reactions: Prospective Evidence in a Realistic Military Setting

DTIC Science & Technology

2014-01-01

procedures were held constant). After the period of quiet rest, the finger pulse oximeter (MedSource International, Mound, MN) was applied to the left...temperature were then recorded with pulse oximeter (Medline Industries, Inc., Mundelein, IL). Following standard guide- lines (Pickering et al., 2005

Selective and self-guided micro-ablation of tissue with plasmonic nanobubbles

PubMed Central

Lukianova-Hleb, Ekaterina Y.; Koneva, Irina I.; Oginsky, Alexander O.; La Francesca, Saverio; Lapotko, Dmitri O.

2010-01-01

Background The accuracy, selectivity and safety of surgical and laser methods for tissue elimination are often limited at microscale. Materials and methods We developed a novel agent, the plasmonic nanobubble (PNB), for optically guided selective elimination of the target tissue with micrometer precision. PNBs were tested in vitro in the two different models of superficial tumors and vascular plaques. Results PNBs were selectively generated around gold nanoparticles (delivered to the target tissues) with short laser pulses. Monolayers of cancerous cells and atherosclerotic plaque tissue were eliminated with PNBs with micrometer accuracy and without thermal and mechanical damage to collateral normal tissues. The effect of the PNB was dynamically controlled through the fluence of laser pulses (532 nm, duration 0.5 and 10 ns) and was guided through the optical scattering by PNB. Conclusions plasmonic nanobubbles were shown to provide precise, tunable, selective and guided ablation of tissue at a microcscopic level and could be employed as a new generation of surgical tools. PMID:21176913

Selective and self-guided micro-ablation of tissue with plasmonic nanobubbles.

PubMed

Lukianova-Hleb, Ekaterina Y; Koneva, Irina I; Oginsky, Alexander O; La Francesca, Saverio; Lapotko, Dmitri O

2011-03-01

The accuracy, selectivity, and safety of surgical and laser methods for tissue elimination are often limited at microscale. We developed a novel agent, the plasmonic nanobubble (PNB), for optically guided selective elimination of the target tissue with micrometer precision. PNBs were tested in vitro in the two different models of superficial tumors and vascular plaques. PNBs were selectively generated around gold nanoparticles (delivered to the target tissues) with short laser pulses. Monolayers of cancerous cells and atherosclerotic plaque tissue were eliminated with PNBs with micrometer accuracy and without thermal and mechanical damage to collateral normal tissues. The effect of the PNB was dynamically controlled through the fluence of laser pulses (532 nm, duration 0.5 and 10 ns) and was guided through the optical scattering by PNB. Plasmonic nanobubbles were shown to provide precise, tunable, selective, and guided ablation of tissue at a microscopic level and could be employed as a new generation of surgical tools. Copyright © 2011 Elsevier Inc. All rights reserved.

Characterization of levofloxacin non-susceptible clinical Streptococcus pyogenes isolated in the central part of Italy.

PubMed

Petrelli, D; Di Luca, M C; Prenna, M; Bernaschi, P; Repetto, A; Vitali, L A

2014-02-01

We investigated the prevalence, genetics, and clonality of fluoroquinolone non-susceptible isolates of Streptococcus pyogenes in the central part of Italy. S. pyogenes strains (n = 197) were isolated during 2012 from patients with tonsillopharyngitis, skin, wound or invasive infections and screened for fluoroquinolone non-susceptibility (resistance to norfloxacin and levofloxacin minimum inhibitory concentration (MIC) = 2 mg/L) following EUCAST guidelines. First-step topoisomerase parC and gyrA substitutions were investigated using sequencing analysis. Clonality was determined by pulsed field gel electrophoresis (PFGE; SmaI digestion) and by emm typing. The fluoroquinolone non-susceptible phenotype was identified in 18 isolates (9.1 %) and correlated with mutations in parC, but not in gyrA, the most frequent leading to substitution of the serine at position 79 with an alanine. Most of the fluoroquinolone non-susceptible isolates belonged to the emm-type 6, even if other emm-types were also represented (emm75, emm89, and emm2). A significant level of association was measured between PFGE and both emm type and substitutions in parC. The prevalence of fluoroquinolone non-susceptible Streptococcus pyogenes isolates in Italy is of concern and, although the well-known emm type 6 is dominant, other types are appearing and spreading.

Financing to meet community needs: a guide for small hospitals.

PubMed

Wilson, Bill

2009-03-01

To succeed in the current financial markets, small hospitals need flexible project and financing plans. Many small local banks today can offer small hospitals financing solutions on par with what was previously offered only by the country's strongest investment-grade rated banks. Federal assistance through programs such as HUD's Section 242 mortgage insurance program is also a viable option for small hospitals.

Study protocol for a randomised controlled trial of ultrasound-guided pulsed radiofrequency of the genicular nerves in the treatment of patients with osteoarthritis knee pain

PubMed Central

Valentí, Pedro; Hernández, Beatriz; Mir, Bartolome; Aguilar, Jose Luis

2017-01-01

Introduction The goals for the management of patients with osteoarthritis (OA) of the knee are to control pain and to minimise disability. Because the number of patients will increase as the population ages, alternative approaches to alleviate their joint pain other than conventional treatments are necessary. The purpose of this article is to present a refined protocol to determine if there is long-term improvement in pain and function after ultrasound-guided pulsed radiofrequency treatment of the genicular nerves (GNs) in patients with chronic painful knee OA. Methods and analysis This study is a randomised, double-blind, placebo-controlled, parallel design trial. One hundred and forty-two outpatients with OA of the knee will be recruited from Mallorca, Spain. Participants will be randomly allocated into two groups: ultrasound-guided sham GN pulsed radiofrequency without active treatment and ultrasound-guided real GN pulsed radiofrequency. The primary outcome measures will be the observed changes from baseline pain intensity based on visual analogue scale (VAS). The possible changes in the secondary efficacy variables from the baseline as assessed by the Goldberg Anxiety and Depression Scale, pain medication use, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC subscales) and VAS pain intensity are also to be included in the study. These variables will be assessed at baseline, 1 month, 3 months, 6 months and 1 year after treatment. Ethics and dissemination The protocol was approved by the Research Ethic Committee of the Balearic Islands (IB 3223/16 PI). The results will be disseminated in peer-reviewed journals and at scientific conferences. Trial registration Trial registration numberNCT02915120; Pre-results PMID:29102985

Nonlinear guiding of picosecond CO2 laser pulses in atmosphere(Conference Presentation)

NASA Astrophysics Data System (ADS)

Tochitsky, Sergei

2017-05-01

During the last 20 years much attention has been given to the study of propagation of short intense laser pulses for which the peak power exceeds the critical power of self-focusing, Pcr. For a laser power P < Pcr, a dynamic equilibrium between the Kerr self-focusing, diffraction and defocusing caused by laser-ionized plasma result in the production of a high intensity laser filament in air within which a variety of nonlinear optical phenomena are observed. However, research in the 0.8-1 μm range so far has shown a fundamental limitation of guided energy to a few mJ transported within an 100 μm single channel. A long-wavelength, 0 10 μm CO2 laser is a promising candidate for nonlinear guiding because expected high Pcr values according to the modeling should allow for the increase of energy (and therefore power) in a self-guided beam from mJ (GW) to few Joules (TW). During the last decade a significant progress has been achieved in amplification of picosecond pulses to terawatt and recently to <10 TW power level at UCLA and ATF BNL. Such powerful 10 μm lasers open possibility for nonlinear propagation studies in an atmospheric window with high transmission. As a natural first step in a our program on picosecond CO2 laser filamentation, we have made first measurements of Kerr coefficients of air and air constituents around 10 μm. We also undertook direct measurements of n2 of air by analyzing nonlinear self-focusing in air using a 3 ps, 600 GW pulses of the BNL CO2 laser.

Precision guided antiaircraft munition

DOEpatents

Hirschfeld, Tomas B.

1987-01-01

A small diameter, 20 mm to 50 mm, guided projectile is used in antiaircraft defense. A pulsing laser designator illuminates the target aircraft. Energy reflected from the aircraft is received by the guided projectile. The guided projectile is fired from a standard weapon but the spining caused by the riflings are removed before active tracking and guidance occurs. The received energy is focused by immersion optics onto a bridge cell. AC coupling and gating removes background and allows steering signals to move extended vanes by means of piezoelectric actuators in the rear of the guided projectile.

1030-nm diode-laser-based light source delivering pulses with nanojoule energies and picosecond duration adjustable by mode locking or pulse gating operation

NASA Astrophysics Data System (ADS)

Klehr, A.; Liero, A.; Wenzel, H.; Bugge, F.; Brox, O.; Fricke, J.; Ressel, P.; Knigge, A.; Heinrich, W.; Tränkle, G.

2017-02-01

A new compact 1030 nm picosecond light source which can be switched between pulse gating and mode locking operation is presented. It consists of a multi-section distributed Bragg reflector (DBR) laser, an ultrafast multisection optical gate and a flared power amplifier (PA), mounted together with high frequency electronics and optical elements on a 5×4 cm micro bench. The master oscillator (MO) is a 10 mm long ridge wave-guide (RW) laser consisting of 200 μm long saturable absorber, 1500 μm long gain, 8000 μm long cavity, 200 μm long DBR and 100 μm long monitor sections. The 2 mm long optical gate consisting of several RW sections is monolithically integrated with the 4 mm long gain-guided tapered amplifier on a single chip. The light source can be switched between pulse gating and passive mode locking operation. For pulse gating all sections of the MO (except of the DBR and monitor sections) are forward biased and driven by a constant current. By injecting electrical pulses into one section of the optical gate the CW beam emitted by the MO is converted into a train of optical pulses with adjustable widths between 250 ps and 1000 ps. Peak powers of 20 W and spectral linewidths in the MHz range are achieved. Shorter pulses with widths between 4 ps and 15 ps and peak powers up to 50 W but larger spectral widths of about 300 pm are generated by mode locking where the saturable absorber section of the MO is reversed biased. The repetition rate of 4.2 GHz of the pulse train emitted by the MO can be reduced to values between 1 kHz and 100 MHz by utilizing the optical gate as pulse picker. The pulse-to-pulse distance can be controlled by an external trigger source.

Laser guiding of Tesla coil high voltage discharges.

PubMed

Henriksson, Markus; Daigle, Jean-Francois; Théberge, Francis; Châteauneuf, Marc; Dubois, Jacques

2012-06-04

We have investigated the guiding and triggering of discharges from a Tesla coil type 280 kHz AC high voltage source using filaments created by a femtosecond Terawatt laser pulse. Without the laser the discharges were maximum 30 cm long. With the laser straight, guided discharges up to 110 cm length were detected. The discharge length was limited by the voltage amplitude of the Tesla coil.

Tolerance of chufa (Cyperus esculentus) as a vegetation unit's representative of bioregenerative life support systems to elevated temperatures

NASA Astrophysics Data System (ADS)

Shklavtsova, Ekaterina; Ushakova, Sofya; Shikhov, Valentin; Kudenko, Yurii

Plants inclusion in the photosynthesizing unit of bioregenerative life support systems (BLSS) expects knowledge of both production characteristics of plants cultivated under optimal condi-tions and their tolerance to stress-factors' effect caused by contingency origination in a system. The work was aimed at investigation of chufa (Cyperus esculentus) tolerance to the effect of super optimal air temperature of 44 subject to PAR intensity and exposure duration. Chufa was grown in light culture conditions by hydroponics method on expanded clay aggregate. The Knop solution was used as nutrition medium. Up to 30 days the plants were cultivated at the intensity of 690 micromole*m-2*s*-1 and air temperature of 25. Heat shock was employed at the age of 30 days under the air temperature of 44 during 7, 20 and 44 hours at two different PAR intensities of 690 and 1150 micromole*m-2*s*-1. Chufa heat tolerance was estimated by intensity of external 2 gas exchange and by state of leaves' photosynthetic apparatus (PSA). Effect of disturbing temperature during 44 hours at PAR intensity of 690 micromole*m-2*s*-1 resulted in frozen-in damage of PSA-leaves' die-off. Chufa plants exposed to heat stress at PAR intensity of 690 micromole*m-2*s*-1 during both 7 and 20-hours demonstrated respiration dominance over photosynthesis; and 2 emission was observed by light. Functional activity of photosynthetic apparatus estimated with respect to parameters of pulse-amplitude-modulated chlorophyll fluorescence of photosystem 2 (PS 2) decreased on 40

Interactive Effects of Temperature and UV Radiation on Photosynthesis of Chlorella Strains from Polar, Temperate and Tropical Environments: Differential Impacts on Damage and Repair

PubMed Central

Wong, Chiew-Yen; Teoh, Ming-Li; Phang, Siew-Moi; Lim, Phaik-Eem; Beardall, John

2015-01-01

Global warming and ozone depletion, and the resulting increase of ultraviolet radiation (UVR), have far-reaching impacts on biota, especially affecting the algae that form the basis of the food webs in aquatic ecosystems. The aim of the present study was to investigate the interactive effects of temperature and UVR by comparing the photosynthetic responses of similar taxa of Chlorella from Antarctic (Chlorella UMACC 237), temperate (Chlorella vulgaris UMACC 248) and tropical (Chlorella vulgaris UMACC 001) environments. The cultures were exposed to three different treatments: photosynthetically active radiation (PAR; 400–700 nm), PAR plus ultraviolet-A (320–400 nm) radiation (PAR + UV-A) and PAR plus UV-A and ultraviolet-B (280–320 nm) radiation (PAR + UV-A + UV-B) for one hour in incubators set at different temperatures. The Antarctic Chlorella was exposed to 4, 14 and 20°C. The temperate Chlorella was exposed to 11, 18 and 25°C while the tropical Chlorella was exposed to 24, 28 and 30°C. A pulse-amplitude modulated (PAM) fluorometer was used to assess the photosynthetic response of microalgae. Parameters such as the photoadaptive index (Ek) and light harvesting efficiency (α) were determined from rapid light curves. The damage (k) and repair (r) rates were calculated from the decrease in ΦPSIIeff over time during exposure response curves where cells were exposed to the various combinations of PAR and UVR, and fitting the data to the Kok model. The results showed that UV-A caused much lower inhibition than UV-B in photosynthesis in all Chlorella isolates. The three isolates of Chlorella from different regions showed different trends in their photosynthesis responses under the combined effects of UVR (PAR + UV-A + UV-B) and temperature. In accordance with the noted strain-specific characteristics, we can conclude that the repair (r) mechanisms at higher temperatures were not sufficient to overcome damage caused by UVR in the Antarctic Chlorella strain, suggesting negative effects of global climate change on microalgae inhabiting (circum-) polar regions. For temperate and tropical strains of Chlorella, damage from UVR was independent of temperature but the repair constant increased with increasing temperature, implying an improved ability of these strains to recover from UVR stress under global warming. PMID:26427046

Interactive Effects of Temperature and UV Radiation on Photosynthesis of Chlorella Strains from Polar, Temperate and Tropical Environments: Differential Impacts on Damage and Repair.

PubMed

Wong, Chiew-Yen; Teoh, Ming-Li; Phang, Siew-Moi; Lim, Phaik-Eem; Beardall, John

2015-01-01

Global warming and ozone depletion, and the resulting increase of ultraviolet radiation (UVR), have far-reaching impacts on biota, especially affecting the algae that form the basis of the food webs in aquatic ecosystems. The aim of the present study was to investigate the interactive effects of temperature and UVR by comparing the photosynthetic responses of similar taxa of Chlorella from Antarctic (Chlorella UMACC 237), temperate (Chlorella vulgaris UMACC 248) and tropical (Chlorella vulgaris UMACC 001) environments. The cultures were exposed to three different treatments: photosynthetically active radiation (PAR; 400-700 nm), PAR plus ultraviolet-A (320-400 nm) radiation (PAR + UV-A) and PAR plus UV-A and ultraviolet-B (280-320 nm) radiation (PAR + UV-A + UV-B) for one hour in incubators set at different temperatures. The Antarctic Chlorella was exposed to 4, 14 and 20°C. The temperate Chlorella was exposed to 11, 18 and 25°C while the tropical Chlorella was exposed to 24, 28 and 30°C. A pulse-amplitude modulated (PAM) fluorometer was used to assess the photosynthetic response of microalgae. Parameters such as the photoadaptive index (Ek) and light harvesting efficiency (α) were determined from rapid light curves. The damage (k) and repair (r) rates were calculated from the decrease in ΦPSIIeff over time during exposure response curves where cells were exposed to the various combinations of PAR and UVR, and fitting the data to the Kok model. The results showed that UV-A caused much lower inhibition than UV-B in photosynthesis in all Chlorella isolates. The three isolates of Chlorella from different regions showed different trends in their photosynthesis responses under the combined effects of UVR (PAR + UV-A + UV-B) and temperature. In accordance with the noted strain-specific characteristics, we can conclude that the repair (r) mechanisms at higher temperatures were not sufficient to overcome damage caused by UVR in the Antarctic Chlorella strain, suggesting negative effects of global climate change on microalgae inhabiting (circum-) polar regions. For temperate and tropical strains of Chlorella, damage from UVR was independent of temperature but the repair constant increased with increasing temperature, implying an improved ability of these strains to recover from UVR stress under global warming.

New laser surface treatments: cleaning, derusting, deoiling, depainting, deoxidizing, and degreasing

NASA Astrophysics Data System (ADS)

Daurelio, Giuseppe; Chita, Giuseppe; Cinquepalmi, Massimo

1997-08-01

Many materials as substrates and surface products have been tested. Typically ferrous (Carbon Steels and Stainless Steels) and non ferrous (Al and Cu metals and its alloys) ones have been employed. Some epoxy, polyurethane, polyester and acrylic paints in different thickness and color have been tested. Many types of the surface rust and oxide on different bulk material have been undertaken to test. Similarly some different types of oils and greases, usually used in industry against the oxidation, have been studied. Anyway many types of dirt, grit, calcareous one and so on, present on industrial components, have been laser cleaned without using solvents, acid baths and other ones. Different types of laser sources have been employed: an axial fast flow, 1.5 KW CO2 c.w. and pulsed laser source, emitting a 10.6 micrometers beam; a portable CO2 laser, c.w. (1 to 25 W) and pulsed (1 to 100 Hz and 400 ms max pulse duration) source, emitting a 10.6 micrometers beam with a multi-articulated seven mirrors guiding device and focussing head; a portable Nd-YAG laser, Q-switched and normal-mode source. 1st harmonic 1.06 micrometers (6 ns pulse duration), 2nd harmonic 532 nm (120 microsecond(s) duration pulse- 1J max per-pulse) wavelengths, multi-articulated seven mirrors beam guiding device, 20 Hz repetition rate. This lets shots with 600 mJ max energy per pulse and 100 MW peak power per-pulse with a very low beam divergence, 0.5 mrad at full angle; a transverse fast flow 2.5 kW CO2 laser.

Noninvasive Label-Free Detection of Micrometastases in the Lymphatics with Ultrasound-Guided Photoacoustic Imaging

DTIC Science & Technology

2015-10-01

imaging can be used to guide dissection. We have also successfully integrated a programmable ultrasound machine (Verasonics Vantage ) and tunable pulsed...Mobile HE) with the programmable ultrasound machine (Verasonics Vantage ). We have synchronized the signals to enable interleaved acquisition of US

In the (sub)tropics allergic rhinitis and its impact on asthma classification of allergic rhinitis is more useful than perennial-seasonal classification.

PubMed

Larenas-Linnemann, Désirée; Michels, Alexandra; Dinger, Hanna; Arias-Cruz, Alfredo; Ambriz Moreno, Marichuy; Bedolla Barajas, Martin; Javier, Ruth Cerino; Cid Del Prado, Maria de la Luz; Cruz Moreno, Manuel Alejandro; Vergara, Laura Diego; García Almaráz, Roberto; García-Cobas, Cecilia Y; Garcia Imperial, Daniel Alberto; Muñoz, Rosa Garcia; Hernandez Colín, Dante; Linares Zapien, Francisco Javier; Luna Pech, Jorge Agustín; Matta Campos, Juan Jose; Martinez Jimenez, Norma; Avalos, Miguel Medina; Medina Hernandez, Alejandra; Maldonado, Albero Monteverde; López, Doris Nereida; Pizano Nazara, Luis Julian; Sanchez, Emanuel Ramirez; Ramos López, José Domingo; Rodriguez-Pérez, Noel; Rodriguez Ortiz, Pablo G; Shah-Hosseini, Kijawasch; Mösges, Ralph

2014-01-01

Two different allergic rhinitis (AR) symptom phenotype classifications exist. Treatment recommendations are based on intermittent-persistent (INT-PER) cataloging, but clinical trials still use the former seasonal AR-perennial AR (SAR-PAR) classification. This study was designed to describe how INT-PER, mild-moderate/severe and SAR-PAR of patients seen by allergists are distributed over the different climate zones in a (sub)tropical country and how these phenotypes relate to allergen sensitization patterns. Six climate zones throughout Mexico were determined, based on National Geographic Institute (Instituto Nacional de Estadística y Geografía) data. Subsequent AR patients (2-68 years old) underwent a blinded, standardized skin-prick test and filled out a validated questionnaire phenotyping AR. Five hundred twenty-nine subjects participated in this study. In the tropical zone with 87% house-dust mite sensitization, INT (80.9%; p < 0.001) and PAR (91%; p = 0.04) were more frequent than in the subtropics. In the central high-pollen areas, there was less moderate/severe AR (65.5%; p < 0.005). Frequency of comorbid asthma showed a clear north-south gradient, from 25% in the dry north to 59% in the tropics (p < 0.005). No differences exist in AR cataloging among patients with different sensitization patterns, with two minor exceptions (more PER in tree sensitized and more PAR in mold positives; p < 0.05). In a (sub)tropical country the SAR-PAR classification seems of limited value and bears poor relation with the INT-PER classification. INT is more frequent in the tropical zone. Because PER has been shown to relate to AR severity, clinical trials should select patients based on INT-PER combined with the severity cataloging because these make for a better treatment guide than SAR-PAR.

Manipulation of optical-pulse-imprinted memory in a Λ system

NASA Astrophysics Data System (ADS)

Gutiérrez-Cuevas, Rodrigo; Eberly, Joseph H.

2015-09-01

We examine coherent memory manipulation in a Λ -type medium, using the second-order solution presented by Groves, Clader, and Eberly [J. Phys. B: At. Mol. Opt. Phys. 46, 224005 (2013), 10.1088/0953-4075/46/22/224005] as a guide. The analytical solution obtained using the Darboux transformation and a nonlinear superposition principle describes complicated soliton-pulse dynamics which, by an appropriate choice of parameters, can be simplified to a well-defined sequence of pulses interacting with the medium. In this report, this solution is reviewed and put to test by means of a series of numerical simulations, encompassing all the parameter space and adding the effects of homogeneous broadening due to spontaneous emission. We find that even though the decohered results deviate from the analytical prediction they do follow a similar trend that could be used as a guide for future experiments.

Multistage Coupling of Laser-Wakefield Accelerators with Curved Plasma Channels.

PubMed

Luo, J; Chen, M; Wu, W Y; Weng, S M; Sheng, Z M; Schroeder, C B; Jaroszynski, D A; Esarey, E; Leemans, W P; Mori, W B; Zhang, J

2018-04-13

Multistage coupling of laser-wakefield accelerators is essential to overcome laser energy depletion for high-energy applications such as TeV-level electron-positron colliders. Current staging schemes feed subsequent laser pulses into stages using plasma mirrors while controlling electron beam focusing with plasma lenses. Here a more compact and efficient scheme is proposed to realize the simultaneous coupling of the electron beam and the laser pulse into a second stage. A partly curved channel, integrating a straight acceleration stage with a curved transition segment, is used to guide a fresh laser pulse into a subsequent straight channel, while the electrons continue straight. This scheme benefits from a shorter coupling distance and continuous guiding of the electrons in plasma while suppressing transverse beam dispersion. Particle-in-cell simulations demonstrate that the electron beam from a previous stage can be efficiently injected into a subsequent stage for further acceleration while maintaining high capture efficiency, stability, and beam quality.

Multistage Coupling of Laser-Wakefield Accelerators with Curved Plasma Channels

NASA Astrophysics Data System (ADS)

Luo, J.; Chen, M.; Wu, W. Y.; Weng, S. M.; Sheng, Z. M.; Schroeder, C. B.; Jaroszynski, D. A.; Esarey, E.; Leemans, W. P.; Mori, W. B.; Zhang, J.

2018-04-01

Multistage coupling of laser-wakefield accelerators is essential to overcome laser energy depletion for high-energy applications such as TeV-level electron-positron colliders. Current staging schemes feed subsequent laser pulses into stages using plasma mirrors while controlling electron beam focusing with plasma lenses. Here a more compact and efficient scheme is proposed to realize the simultaneous coupling of the electron beam and the laser pulse into a second stage. A partly curved channel, integrating a straight acceleration stage with a curved transition segment, is used to guide a fresh laser pulse into a subsequent straight channel, while the electrons continue straight. This scheme benefits from a shorter coupling distance and continuous guiding of the electrons in plasma while suppressing transverse beam dispersion. Particle-in-cell simulations demonstrate that the electron beam from a previous stage can be efficiently injected into a subsequent stage for further acceleration while maintaining high capture efficiency, stability, and beam quality.

Note: Characterization of the plasma parameters of a capillary discharge-produced plasma channel waveguide to guide an intense laser pulse

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

Higashiguchi, Takeshi; Yugami, Noboru; CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kanagawa, Saitama 332-0012

2010-04-15

We demonstrated the production of an optical waveguide in a capillary discharge-produced plasma using a cylindrical capillary. Plasma parameters of its waveguide were characterized by use of both a Nomarski laser interferometer and a hydrogen plasma line spectrum. A space-averaged maximum temperature of 3.3 eV with electron densities of the order of 10{sup 17} cm{sup -3} was observed at a discharge time of 150 ns and a maximum discharge current of 400 A. An ultrashort, intense laser pulse was guided by use of this plasma channel.

Wave Mode Discrimination of Coded Ultrasonic Guided Waves Using Two-Dimensional Compressed Pulse Analysis.

PubMed

Malo, Sergio; Fateri, Sina; Livadas, Makis; Mares, Cristinel; Gan, Tat-Hean

2017-07-01

Ultrasonic guided waves testing is a technique successfully used in many industrial scenarios worldwide. For many complex applications, the dispersive nature and multimode behavior of the technique still poses a challenge for correct defect detection capabilities. In order to improve the performance of the guided waves, a 2-D compressed pulse analysis is presented in this paper. This novel technique combines the use of pulse compression and dispersion compensation in order to improve the signal-to-noise ratio (SNR) and temporal-spatial resolution of the signals. The ability of the technique to discriminate different wave modes is also highlighted. In addition, an iterative algorithm is developed to identify the wave modes of interest using adaptive peak detection to enable automatic wave mode discrimination. The employed algorithm is developed in order to pave the way for further in situ applications. The performance of Barker-coded and chirp waveforms is studied in a multimodal scenario where longitudinal and flexural wave packets are superposed. The technique is tested in both synthetic and experimental conditions. The enhancements in SNR and temporal resolution are quantified as well as their ability to accurately calculate the propagation distance for different wave modes.

Population attributable risk of factors associated with the repetition of self-harm behaviour in young people presenting to clinical services: a systematic review and meta-analysis.

PubMed

Witt, Katrina; Milner, Allison; Spittal, Matthew J; Hetrick, Sarah; Robinson, Jo; Pirkis, Jane; Carter, Gregory

2018-02-03

The repetition of hospital-treated self-harm by young people is common. However, little work has summarised the modifiable factors associated with this. A thorough understanding of those factors most strongly associated with repetition could guide the development of relevant clinical interventions. We systematically reviewed four databases (EMBASE, Medline, PubMed and PsycINFO) until 15 April 2016 to identify all observational studies of factors for the repetition of self-harm or suicide reattempts (together referred to as 'self-harm behaviour') in young people. We quantified the magnitude of association with odds ratios (OR) and 95% confidence intervals (CIs) and calculated the population attributable risk (PAR) and population preventable fraction (PPF) for modifiable factors to provide an indication of the potential impact in reducing subsequent self-harm behaviour in this population. Seventeen studies were included comprising 10,726 participants. Borderline personality disorder (OR 3.47, 95% CI 1.84-6.53; PAR 42.4%), any personality disorder (OR 2.54, 95% CI 1.71-3.78; PAR 16.3%), and any mood disorder (OR 2.16, 95% CI 1.09-4.29; PAR 42.2%) are important modifiable risk factors. Severity of hopelessness (OR 2.95, 95% CI 1.74-5.01), suicidal ideation (OR 2.01, 95% CI 1.43-2.81), and previous sexual abuse (OR 1.52, 95% CI 1.02-2.28; PAR 12.8%) are also associated with repetition of self-harm. We recommend that clinical services should focus on identifying key modifiable risk factors at the individual patient level, whilst the reduction of exposure to child and adolescent sexual abuse would also be a useful goal for public health interventions.

Dual Targeting of GyrB and ParE by a Novel Aminobenzimidazole Class of Antibacterial Compounds▿

PubMed Central

Grossman, Trudy H.; Bartels, Douglas J.; Mullin, Steve; Gross, Christian H.; Parsons, Jonathan D.; Liao, Yusheng; Grillot, Anne-Laure; Stamos, Dean; Olson, Eric R.; Charifson, Paul S.; Mani, Nagraj

2007-01-01

A structure-guided drug design approach was used to optimize a novel series of aminobenzimidazoles that inhibit the essential ATPase activities of bacterial DNA gyrase and topoisomerase IV and that show potent activities against a variety of bacterial pathogens. Two such compounds, VRT-125853 and VRT-752586, were characterized for their target specificities and preferences in bacteria. In metabolite incorporation assays, VRT-125853 inhibited both DNA and RNA synthesis but had little effect on protein synthesis. Both compounds inhibited the maintenance of negative supercoils in plasmid DNA in Escherichia coli at the MIC. Sequencing of DNA corresponding to the GyrB and ParE ATP-binding regions in VRT-125853- and VRT-752586-resistant mutants revealed that their primary target in Staphylococcus aureus and Haemophilus influenzae was GyrB, whereas in Streptococcus pneumoniae it was ParE. In Enterococcus faecalis, the primary target of VRT-125853 was ParE, whereas for VRT-752586 it was GyrB. DNA transformation experiments with H. influenzae and S. aureus proved that the mutations observed in gyrB resulted in decreased susceptibilities to both compounds. Novobiocin resistance-conferring mutations in S. aureus, H. influenzae, and S. pneumoniae were found in gyrB, and these mutants showed little or no cross-resistance to VRT-125853 or VRT-752586 and vice versa. Furthermore, gyrB and parE double mutations increased the MICs of VRT-125853 and VRT-752586 significantly, providing evidence of dual targeting. Spontaneous frequencies of resistance to VRT-752586 were below detectable levels (<5.2 × 10−10) for wild-type E. faecalis but were significantly elevated for strains containing single and double target-based mutations, demonstrating that dual targeting confers low levels of resistance emergence and the maintenance of susceptibility in vitro. PMID:17116675

Dual targeting of GyrB and ParE by a novel aminobenzimidazole class of antibacterial compounds.

PubMed

Grossman, Trudy H; Bartels, Douglas J; Mullin, Steve; Gross, Christian H; Parsons, Jonathan D; Liao, Yusheng; Grillot, Anne-Laure; Stamos, Dean; Olson, Eric R; Charifson, Paul S; Mani, Nagraj

2007-02-01

A structure-guided drug design approach was used to optimize a novel series of aminobenzimidazoles that inhibit the essential ATPase activities of bacterial DNA gyrase and topoisomerase IV and that show potent activities against a variety of bacterial pathogens. Two such compounds, VRT-125853 and VRT-752586, were characterized for their target specificities and preferences in bacteria. In metabolite incorporation assays, VRT-125853 inhibited both DNA and RNA synthesis but had little effect on protein synthesis. Both compounds inhibited the maintenance of negative supercoils in plasmid DNA in Escherichia coli at the MIC. Sequencing of DNA corresponding to the GyrB and ParE ATP-binding regions in VRT-125853- and VRT-752586-resistant mutants revealed that their primary target in Staphylococcus aureus and Haemophilus influenzae was GyrB, whereas in Streptococcus pneumoniae it was ParE. In Enterococcus faecalis, the primary target of VRT-125853 was ParE, whereas for VRT-752586 it was GyrB. DNA transformation experiments with H. influenzae and S. aureus proved that the mutations observed in gyrB resulted in decreased susceptibilities to both compounds. Novobiocin resistance-conferring mutations in S. aureus, H. influenzae, and S. pneumoniae were found in gyrB, and these mutants showed little or no cross-resistance to VRT-125853 or VRT-752586 and vice versa. Furthermore, gyrB and parE double mutations increased the MICs of VRT-125853 and VRT-752586 significantly, providing evidence of dual targeting. Spontaneous frequencies of resistance to VRT-752586 were below detectable levels (<5.2x10(-10)) for wild-type E. faecalis but were significantly elevated for strains containing single and double target-based mutations, demonstrating that dual targeting confers low levels of resistance emergence and the maintenance of susceptibility in vitro.

Advanced Photon Source accelerator ultrahigh vacuum guide

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

Liu, C.; Noonan, J.

1994-03-01

In this document the authors summarize the following: (1) an overview of basic concepts of ultrahigh vacuum needed for the APS project, (2) a description of vacuum design and calculations for major parts of APS, including linac, linac waveguide, low energy undulator test line, positron accumulator ring (PAR), booster synchrotron ring, storage ring, and insertion devices, and (3) cleaning procedures of ultrahigh vacuum (UHV) components presently used at APS.

Electrocatalytic oxidation and voltammetric determination of ciprofloxacin employing poly(alizarin red)/graphene composite film in the presence of ascorbic acid, uric acid and dopamine.

PubMed

Zhang, Xin; Wei, Youli; Ding, Yaping

2014-07-04

A glassy carbon electrode modified with poly(alizarin red)/electrodeposited graphene (PAR/EGR) composite film was prepared and applied to detect ciprofloxacin (CPFX) in the presence of ascorbic, uric acid and dopamine. The morphology and interface property of PAR/EGR films were examined by scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS). The electrocatalytic oxidation of CPFX on AR/EGR was investigated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The linearity ranged from 4 × 10(-8) to 1.2 × 10(-4) M with a detection limit (S/N=3) of 0.01 μM. The modified electrode could be applied to the individual determination of CPFX as well as the simultaneous determination of CPFX, ascorbic acid, uric acid and dopamine. This method proved to be a simple, selective and rapid way to determine CPFX in pharmaceutical preparation and biological media. Copyright © 2014. Published by Elsevier B.V.

On the feasibility of a fiber-based inertial fusion laser driver

NASA Astrophysics Data System (ADS)

Labaune, C.; Hulin, D.; Galvanauskas, A.; Mourou, G. A.

2008-08-01

One critical issue for the realization of Inertial Fusion Energy (IFE) power plants is the driver efficiency. High driver efficiency will greatly relax the driver energy requested to produce a fusion gain, resulting in more compact and less costly facilities. Among lasers, systems based on guided wave such as diode pumped Yb:glass fiber-amplifiers with a demonstrated overall efficiency close to 70% as opposed to few percents for systems based on free propagation, offer some intriguing opportunities. Guided optics provides the enormous advantage to directly benefit from the telecommunication industry where components are made cheap, rugged, well tested, environmentally stable, with lifetimes measured in tens of years and compatible with massive manufacturing. In this paper, we are studying the possibility to design a laser driver solely based on guided wave optics. We call this concept FAN for Fiber Amplification Network. It represents a profound departure from already proposed laser drivers all based on free propagation optics. The system will use a large number of identical fibers to combines long (ns) and short (ps) pulses that are needed for the fast ignition scheme. Technical details are discussed relative to fiber type, pump, phasing, pulse shaping and timing as well as fiber distribution around the chamber. The proposed fiber driver provides maximum and independent control on the wavefront, pulse duration, pulse shape, timing, making possible reaching the highest gain. The massive manufacturing will be amenable to a cheaper facility with an easy upkeep.

Randomized and controlled prospective trials of Ultrasound-guided spinal nerve posterior ramus pulsed radiofrequency treatment for lower back post-herpetic neuralgia.

PubMed

Pi, Z B; Lin, H; He, G D; Cai, Z; Xu, X Z

2015-01-01

To evaluate the efficacy of ultrasound-guided spinal nerve posterior ramus pulsed radiofrequency treatment for lower back post-herpetic neuralgia. 128 cases of lower back or anterior abdominal wall acute post-herpetic neuralgia patients were selected. They were randomly divided into two groups. Group A: oral treatment only with gabapentin + celecoxib + amitriptyline. Group B: while taking these drugs, patients were treated with radiofrequency (RF) pulses using a portable ultrasound device using the paravertebral puncture technique. In both groups, sudden outbreaks of pain were treated with immediate release 10mg morphine tablets. Visual analogue scale (VAS) was used for pain score, Pittsburgh Sleep Quality Index scale (PSQI) was used to evaluate sleep quality and morphine consumption were recorded at different time points, before and after treatment. Treatment efficiency was calculated while the occurrence of complications was documented. At each time point after treatment, VAS scores were lower, but scores in the RF group was significantly lower than those of the oral-only group. In terms of sleep quality scores and morphine consumption between the two groups, the RF group was significantly lower than the oral-only group. During the procedure no error occurred with needle penetrating the abdominal cavity, chest, offal or blood vessels. Ultrasound-guided spinal nerve posterior ramus pulsed radiofrequency treatment of lower back or anterior abdominal wall post-herpetic neuralgia proved effective by reducing morphine use in patients and led to fewer adverse reactions.

A simulation model for predicting the temperature during the application of MR-guided focused ultrasound for stroke treatment using pulsed ultrasound

NASA Astrophysics Data System (ADS)

Hadjisavvas, V.; Damianou, C.

2011-09-01

In this paper a simulation model for predicting the temperature during the application of MR-guided focused ultrasound for stroke treatment using pulsed ultrasound is presented. A single element spherically focused transducer of 5 cm diameter, focusing at 10 cm and operating at either 0.5 MHz or 1 MHz was considered. The power field was estimated using the KZK model. The temperature was estimated using the bioheat equation. The goal was to extract the acoustic parameters (power, pulse duration, duty factor and pulse repetition frequency) that maintain a temperature increase of less than 1 °C during the application of a pulse ultrasound protocol. It was found that the temperature change increases linearly with duty factor. The higher the power, the lower the duty factor needed to keep the temperature change to the safe limit of 1 °C. The higher the frequency the lower the duty factor needed to keep the temperature change to the safe limit of 1 °C. Finally, the deeper the target, the higher the duty factor needed to keep the temperature change to the safe limit of 1 °C. The simulation model was tested in brain tissue during the application of pulse ultrasound and the measured temperature was in close agreement with the simulated temperature. This simulation model is considered to be very useful tool for providing acoustic parameters (frequency, power, duty factor, pulse repetition frequency) during the application of pulsed ultrasound at various depths in tissue so that a safe temperature is maintained during the treatment. This model could be tested soon during stroke clinical trials.

The best marker for guiding the clinical management of patients with raised intracranial pressure-the RAP index or the mean pulse amplitude?

PubMed

Hall, Allan; O'Kane, Roddy

2016-10-01

Raised intracranial pressure is a common problem in a variety of neurosurgical conditions including traumatic brain injury, hydrocephalus and intracranial haemorrhage. The clinical management of these patients is guided by a variety of haemodynamic, biochemical and clinical factors. However to date there is no single parameter that is used to guide clinical management of patients with raised intracranial pressure (ICP). However, the role of ICP indices, specifically the mean pulse amplitude (AMP) and RAP index [correlation coefficient (R) between AMP amplitude (A) and mean ICP pressure (P); index of compensatory reserve], as an indicator of true ICP has been investigated. Whilst the RAP index has been used both as a descriptor of neurological deterioration in TBI patients and as a way of characterising the compensatory reserve in hydrocephalus, more recent studies have highlighted the limitation of the RAP index due to the influence that baseline effect errors have on the mean ICP, which is used in the calculation of the RAP index. These studies have suggested that the ICP mean pulse amplitude may be a more accurate marker of true intracranial pressure due to the fact that it is uninfluenced by the mean ICP and, therefore, the AMP may be a more reliable marker than the RAP index for guiding the clinical management of patients with raised ICP. Although further investigation needs to be undertaken in order to fully assess the role of ICP indices in guiding the clinical management of patients with raised ICP, the studies undertaken to date provide an insight into the potential role of ICP indices to treat raised ICP proactively rather than reactively and therefore help prevent or minimise secondary brain injury.

Coronary CT Angiography Incorporating Doppler-Guided Prospective ECG Gating in Patients with High Heart Rate: Comparison with Results of Traditional Prospective ECG Gating

PubMed Central

Li, Min; Yu, Bing-bing; Wu, Jian-hua; Xu, Lin; Sun, Gang

2013-01-01

Purpose As Doppler ultrasound has been proven to be an effective tool to predict and compress the optimal pulsing windows, we evaluated the effective dose and diagnostic accuracy of coronary CT angiography (CTA) incorporating Doppler-guided prospective electrocardiograph (ECG) gating, which presets pulsing windows according to Doppler analysis, in patients with a heart rate >65 bpm. Materials and Methods 119 patients with a heart rate >65 bpm who were scheduled for invasive coronary angiography were prospectively studied, and patients were randomly divided into traditional prospective (n = 61) and Doppler-guided prospective (n = 58) ECG gating groups. The exposure window of traditional prospective ECG gating was set at 30%–80% of the cardiac cycle. For the Doppler group, the length of diastasis was analyzed by Doppler. For lengths greater than 90 ms, the pulsing window was preset during diastole (during 60%–80%); otherwise, the optimal pulsing intervals were moved from diastole to systole (during 30%–50%). Results The mean heart rates of the traditional ECG and the Doppler-guided group during CT scanning were 75.0±7.7 bpm (range, 66–96 bpm) and 76.5±5.4 bpm (range: 66–105 bpm), respectively. The results indicated that whereas the image quality showed no significant difference between the traditional and Doppler groups (P = 0.42), the radiation dose of the Doppler group was significantly lower than that of the traditional group (5.2±3.4mSv vs. 9.3±4.5mSv, P<0.001). The sensitivities of CTA applying traditional and Doppler-guided prospective ECG gating to diagnose stenosis on a segment level were 95.5% and 94.3%, respectively; specificities 98.0% and 97.1%, respectively; positive predictive values 90.7% and 88.2%, respectively; negative predictive values 99.0% and 98.7%, respectively. There was no statistical difference in concordance between the traditional and Doppler groups (P = 0.22). Conclusion Doppler-guided prospective ECG gating represents an improved method in patients with a high heart rate to reduce effective radiation doses, while maintaining high diagnostic accuracy. PMID:23696793

Measurement of electron density transients in pulsed RF discharges using a frequency boxcar hairpin probe

NASA Astrophysics Data System (ADS)

Peterson, David; Coumou, David; Shannon, Steven

2015-11-01

Time resolved electron density measurements in pulsed RF discharges are shown using a hairpin resonance probe using low cost electronics, on par with normal Langmuir probe boxcar mode operation. Time resolution of 10 microseconds has been demonstrated. A signal generator produces the applied microwave frequency; the reflected waveform is passed through a directional coupler and filtered to remove the RF component. The signal is heterodyned with a frequency mixer and rectified to produce a DC signal read by an oscilloscope. At certain points during the pulse, the plasma density is such that the applied frequency is the same as the resonance frequency of the probe/plasma system, creating reflected signal dips. The applied microwave frequency is shifted in small increments in a frequency boxcar routine to determine the density as a function of time. A dc sheath correction is applied for the grounded probe, producing low cost, high fidelity, and highly reproducible electron density measurements. The measurements are made in both inductively and capacitively coupled systems, the latter driven by multiple frequencies where a subset of these frequencies are pulsed. Measurements are compared to previous published results, time resolved OES, and in-line measurement of plasma impedance. This work is supported by the NSF DOE partnership on plasma science, the NSF GOALI program, and MKS Instruments.

[Sap flux density in response to rainfall pulses for Pinus tabuliformis and Hippophae rhamnoides from mixed plantation in hilly Loess Plateau].

PubMed

Lu, Sen Bao; Chen, Yun Ming; Tang, Ya Kun; Wu, Xu; Wen, Jie

2017-11-01

Thermal dissipation probe (TDP) was used to continuously measure the sap flux density (F d ) of Pinus tabuliformis and Hippophae rhamnoides individuals in hilly Loess Plateau, from June to October 2015, and the environmental factors, i.e., photosynthetic active radiation (PAR), water vapor pressure deficit (VPD), and soil water content (SWC), were simultaneously monitored to clarify the difference of rainfall utilization between the two tree species in a mixed plantation. Using the methods of a Threshold-delay model, stepwise multiple regression analyses, and partial correlation analyses, this paper studied the process of F d in these two species in response to the rainfall pulses and then determined the effects of environmental factors on F d . The results showed that, with the increase of rainfall, the response percentages of F d in both P. tabuliformis and H. rhamnoides increased at first but then decreased; specifically, in the range of 0-1 mm rainfall, the F d of P. tabuliformis (-16.3%) and H. rhamnoides (-6.3%) clearly decreased; in the range of 1-5 mm rainfall, the F d of P. tabuliformis decreased (-0.4%), whereas that of H. rhamnoides significantly increased (9.0%). The lower rainfall thresholds (R L ) of F d for P. tabuliformis and H. rhamnoides were 6.4 and 1.9 mm, respectively, with a corresponding time-lag (τ) of 1.96 and 1.67 days. In the pre-rainfall period, the peak time of F d of P. tabuliformis converged upon 12:00-12:30 (70%), while the F d of H. rhamnoides peaked twice, between 10:30 and 12:00 (48%) and again between 16:00 and 16:30 (30%). In the post-rainfall period, the peak time of F d of P. tabuliformis converged upon 11:00-13:00 (40%), while that of H. rhamnoides peaked twice, between 12:00 and 13:00 (52%) and again between 16:30 and 17:00 (24%). Among the environmental factors, the rank order of factors associated with the F d of both P. tabuliformis and H. rhamnoides was PAR>VPD, before rainfall. However, the rank order of factors influencing the F d of P. tabuliformis was PAR>VPD>0-20 cm SWC (SWC 0-20 ), whereas this order was different for H. rhamnoides: SWC 0-20 >PAR >VPD, after rainfall. This mixed plantation of P. tabuliformis and H. rhamnoides trees had a high stability of water utilization.

Photoinhibition in common atlantic macroalgae measured on site in Gran Canaria

NASA Astrophysics Data System (ADS)

Häder, D.-P.; Porst, M.; Lebert, M.

2001-03-01

The photosynthetic quantum yield was analysed in four common atlantic macroalgae, the Rhodophytes Gelidium arbuscula and Halopithys incurvus and the Phaeophytes Halopteris scoparia and Lobophora variegata in Gran Canaria, Canary Islands at their growth site. The fluorescence parameters were measured using a portable pulse amplitude modulated (PAM) fluorometer (PAM 2000) instrument and a diving PAM under water without removing the thalli from their growth sites. Solar radiation was monitored continuously above and under water during the whole experimental period using two three-channel dosimeters (European light dosimeter network; ELDONET) (Real Time Computer, Möhrendorf, Germany). These instruments measure solar radiation in three wavelength ranges, ultraviolet (UV)-A, UV-B and photosynthetic active radiation (PAR). In all four algae the effective photosynthetic quantum yield decreased significantly from the optimal values measured after dark adaptation due to exposure to 15 min solar radiation, but at least partially recovered subsequently in the shade within several hours. Increasing the exposure period to 30 min intensified the photoinhibition. In some algae no recovery was observed after this treatment and in others no significant recovery could be detected. Exposure to unfiltered solar radiation caused a significantly higher photoinhibition than PAR-only radiation or PAR plus UV-A. A substantial inhibition was found in all algae at their growth sites in the water column when the sun was at high angles, as measured with the diving PAM.

Kerr effect in the isotropic phase of a side-chain polymeric liquid crystal

NASA Astrophysics Data System (ADS)

Reys, V.; Dormoy, Y.; Collin, D.; Keller, P.; Martinoty, P.

1992-02-01

The birefringence induced by a pulsed electrical field was used to study the pretransitional effects associated with the isotropic phase of a side-chain polysiloxane. The results obtained show that these effects are characterised by a conventional value of the static exponent and an abnormal value of the dynamic exponent, which shows that the dynamic theory of low molecular weight liquid crystals does not apply. The results also reveal competition between the dipolar moments induced by the electrical field and the permanent moments of the mesogenic molecules. La biréfringence induite par un champ électrique impulsionnel a été utilisée pour étudier les effets prétransitionnels associés à la phase isotrope d'un polysiloxane à chaînes latérales. Les résultats obtenus montrent que ces effets sont caractérisés par une valeur classique de l'exposant statique et une valeur anormale de l'exposant dynamique. Ce dernier résultat montre que la théorie dynamique des cristaux liquides de bas poids moléculaire n'est pas applicable au cas présent. Les expériences mettent également en évidence une compétition entre les moments dipolaires induits par le champ électrique et les moments permanents des molécules mésogènes.

180 mJ, long-pulse-duration, master-oscillator power amplifier with linewidth less than 25.6 kHz for laser guide stars.

PubMed

Wang, Chunhua; Zhang, Xiang; Ye, Zhibin; Liu, Chong; Chen, Jun

2013-07-01

A high-energy single-frequency hundred-microsecond long-pulse solid-state laser is demonstrated, which features an electro-optically modulated seed laser and two-stage double-passed pulse-pumped solid-state laser rod amplifier. Laser output with energy of 180 mJ, repetition rate of 50 Hz, and pulse width of 150 μs is achieved. The laser linewidth is measured to be less than 25.52 kHz by a fiber delay self-heterodyne method. In addition, a closed-loop controlling system is adopted to lock the center wavelength. No relaxation oscillation spikes appear in the pulse temporal profile, which is beneficial for further amplification.

Controlling Plasma Channels through Ultrashort Laser Pulse Filamentation

NASA Astrophysics Data System (ADS)

Ionin, Andrey; Seleznev, Leonid; Sunchugasheva, Elena

2013-09-01

A review of studies fulfilled at the Lebedev Institute in collaboration with the Moscow State University and Institute of Atmospheric Optics in Tomsk on influence of various characteristics of ultrashort laser pulse on plasma channels formed under its filamentation is presented. Filamentation of high-power laser pulses with wavefront controlled by a deformable mirror, with cross-sections spatially formed by various diaphragms and with different wavelengths was experimentally and numerically studied. An application of plasma channels formed due to filamentation of ultrashort laser pulse including a train of such pulses for triggering and guiding long electric discharges is discussed. The research was supported by RFBR Grants 11-02-12061-ofi-m and 11-02-01100, and EOARD Grant 097007 through ISTC Project 4073 P

A patient-mount navigated intervention system for spinal diseases and its clinical trial on percutaneous pulsed radiofrequency stimulation of dorsal root ganglion.

PubMed

Yang, Chi-Lin; Yang, Been-Der; Lin, Mu-Lien; Wang, Yao-Hung; Wang, Jaw-Lin

2010-10-01

Development of a patient-mount navigated intervention (PaMNI) system for spinal diseases. An in vivo clinical human trial was conducted to validate this system. To verify the feasibility of the PaMNI system with the clinical trial on percutaneous pulsed radiofrequency stimulation of dorsal root ganglion (PRF-DRG). Two major image guiding techniques, i.e., computed tomography (CT)-guided and fluoro-guided, were used for spinal intervention. The CT-guided technique provides high spatial resolution, and is claimed to be more accurate than the fluoro-guided technique. Nevertheless, the CT-guided intervention usually reaches higher radiograph exposure than the fluoro-guided counterpart. Some navigated intervention systems were developed to reduce the radiation of CT-guided intervention. Nevertheless, these systems were not popularly used due to the longer operation time, a new protocol for surgeons, and the availability of such a system. The PaMNI system includes 3 components, i.e., a patient-mount miniature tracking unit, an auto-registered reference frame unit, and a user-friendly image processing unit. The PRF-DRG treatment was conducted to find the clinical feasibility of this system. The in vivo clinical trial showed that the accuracy, visual analog scale evaluation after surgery, and radiograph exposure of the PaMNI-guided technique are comparable to the one of conventional fluoro-guided technique, while the operation time is increased by 5 minutes. Combining the virtues of fluoroscopy and CT-guided techniques, our navigation system is operated like a virtual fluoroscopy with augmented CT images. This system elevates the performance of CT-guided intervention and reduces surgeons' radiation exposure risk to a minimum, while keeping low radiation dose to patients like its fluoro-guided counterpart. The clinical trial of PRF-DRG treatment showed the clinical feasibility and efficacy of this system.

Oxygen saturation profile in healthy preterm infants.

PubMed

Harigopal, S; Satish, H P; Taktak, A F G; Southern, K W; Shaw, N J

2011-09-01

To establish a reference range for oxygen saturation (SpO(2)) in well preterm infants to guide home oxygen therapy using a pulse oximeter and Pulse Oximetry Data Analysis Software (PODS). SpO(2) and heart-rate profiles of healthy preterm infants receiving mechanical ventilation for less than 6 h and supplemental oxygen for less than 48 h were monitored using a pulse oximeter. The stored data were downloaded from the monitor to a personal computer as individual files. Each infant's files of SpO(2) were subsequently displayed in graphic form, and a reference range was constructed using dedicated software, PODS. 43 infants were studied. The median value of all infants mean SpO(2) values was 95% (range 92-99%). The median duration of saturations less than 85% and between 85% and 90 % were 1% and 2% respectively. Using the study group median, 5th and 95th percentiles, a cumulative frequency curve of time against SpO(2) value was constructed (representing the reference range of SpO(2) profiles in healthy preterm infants). The SpO(2) reference range can be used as an easy and practical guide to compare SpO(2) profiles of infants on home oxygen therapy and guide their oxygen therapy.

Measurements of self-guiding of ultrashort laser pulses over long distances

NASA Astrophysics Data System (ADS)

Poder, K.; Cole, J. M.; Wood, J. C.; Lopes, N. C.; Alatabi, S.; Foster, P. S.; Kamperidis, C.; Kononenko, O.; Palmer, C. A.; Rusby, D.; Sahai, A.; Sarri, G.; Symes, D. R.; Warwick, J. R.; Mangles, S. P. D.; Najmudin, Z.

2018-01-01

We report on the evaluation of the performance of self-guiding over extended distances with f/20 and f/40 focussing geometries. Guiding over 39 {mm} or more than 100 Rayleigh ranges was observed with the f/20 optic at {n}e=1.5× {10}18 {{cm}}-3. Analysis of guiding performance found that the extent of the exiting laser spatial mode closely followed the matched spot size predicted by 3D nonlinear theory. Self-guiding with an f/40 optic was also characterised, with guided modes observed for a plasma length of 90 {mm} and a plasma density of {n}e=9.5× {10}17 {{cm}}-3. This corresponds to self-guided propagation over 53 Rayleigh ranges and is similar to distances obtained with discharge plasma channel guiding.

Guided acoustic wave inspection system

DOEpatents

Chinn, Diane J.

2004-10-05

A system for inspecting a conduit for undesirable characteristics. A transducer system induces guided acoustic waves onto said conduit. The transducer system detects the undesirable characteristics of the conduit by receiving guided acoustic waves that contain information about the undesirable characteristics. The conduit has at least two sides and the transducer system utilizes flexural modes of propagation to provide inspection using access from only the one side of the conduit. Cracking is detected with pulse-echo testing using one transducer to both send and receive the guided acoustic waves. Thinning is detected in through-transmission testing where one transducer sends and another transducer receives the guided acoustic waves.

Nanopore formation in neuroblastoma cells following ultrashort electric pulse exposure

NASA Astrophysics Data System (ADS)

Roth, Caleb C.; Payne, Jason A.; Wilmink, Gerald J.; Ibey, Bennett L.

2011-03-01

Ultrashort or nanosecond electrical pulses (USEP) cause repairable damage to the plasma membranes of cells through formation of nanopores. These nanopores are able to pass small ions such as sodium, calcium, and potassium, but remain impermeable to larger molecules like trypan blue and propidium iodide. What remains uncertain is whether generation of nanopores by ultrashort electrical pulses can inhibit action potentials in excitable cells. In this paper, we explored the sensitivity of excitable cells to USEP using Calcium Green AM 1 ester fluorescence to measure calcium uptake indicative of nanopore formation in the plasma membrane. We determined the threshold for nanopore formation in neuroblastoma cells for three pulse parameters (amplitude, pulse width, and pulse number). Measurement of such thresholds will guide future studies to determine if USEP can inhibit action potentials without causing irreversible membrane damage.

Multistage Coupling of Laser-Wakefield Accelerators with Curved Plasma Channel

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

Luo, J.; Chen, M.; Wu, W. Y.

Multistage coupling of laser-wakefield accelerators is essential to overcome laser energy depletion for high-energy applications such as TeV level electron-positron colliders. Current staging schemes feed subsequent laser pulses into stages using plasma mirrors, while controlling electron beam focusing with plasma lenses. Here a more compact and efficient scheme is proposed to realize simultaneous coupling of the electron beam and the laser pulse into a second stage. Furthermore, a curved channel with transition segment is used to guide a fresh laser pulse into a subsequent straight channel, while allowing the electrons to propagate in a straight channel. This scheme then benefitsmore » from a shorter coupling distance and continuous guiding of the electrons in plasma, while suppressing transverse beam dispersion. Within moderate laser parameters, particle-in-cell simulations demonstrate that the electron beam from a previous stage can be efficiently injected into a subsequent stage for further acceleration, while maintaining high capture efficiency, stability, and beam quality.« less

Multistage Coupling of Laser-Wakefield Accelerators with Curved Plasma Channel

DOE PAGES

Luo, J.; Chen, M.; Wu, W. Y.; ...

2018-04-10

Multistage coupling of laser-wakefield accelerators is essential to overcome laser energy depletion for high-energy applications such as TeV level electron-positron colliders. Current staging schemes feed subsequent laser pulses into stages using plasma mirrors, while controlling electron beam focusing with plasma lenses. Here a more compact and efficient scheme is proposed to realize simultaneous coupling of the electron beam and the laser pulse into a second stage. Furthermore, a curved channel with transition segment is used to guide a fresh laser pulse into a subsequent straight channel, while allowing the electrons to propagate in a straight channel. This scheme then benefitsmore » from a shorter coupling distance and continuous guiding of the electrons in plasma, while suppressing transverse beam dispersion. Within moderate laser parameters, particle-in-cell simulations demonstrate that the electron beam from a previous stage can be efficiently injected into a subsequent stage for further acceleration, while maintaining high capture efficiency, stability, and beam quality.« less

Tesla coil discharges guided by femtosecond laser filaments in air

NASA Astrophysics Data System (ADS)

Brelet, Yohann; Houard, Aurélien; Arantchouk, Leonid; Forestier, Benjamin; Liu, Yi; Prade, Bernard; Carbonnel, Jérôme; André, Yves-Bernard; Mysyrowicz, André

2012-04-01

A Tesla coil generator was designed to produce high voltage pulses oscillating at 100 kHz synchronisable with a nanosecond temporal jitter. Using this compact high voltage generator, we demonstrate reproducible meter long discharges in air at a repetition rate of 1 Hz. Triggering and guiding of the discharges are performed in air by femtosecond laser filaments.

Wavelength-Modulated Differential Photoacoustic Spectroscopy (WM-DPAS): Theory of a High-Sensitivity Methodology for the Detection of Early-Stage Tumors in Tissues

NASA Astrophysics Data System (ADS)

Choi, S.; Mandelis, A.; Guo, X.; Lashkari, B.; Kellnberger, S.; Ntziachristos, V.

2015-06-01

In the field of medical diagnostics, biomedical photoacoustics (PA) is a non-invasive hybrid optical-ultrasonic imaging modality. Due to the unique hybrid capability of optical and acoustic imaging, PA imaging has risen to the frontiers of medical diagnostic procedures such as human breast cancer detection. While conventional PA imaging has been mainly carried out by a high-power pulsed laser, an alternative technology, the frequency domain biophotoacoustic radar (FD-PAR) is under intensive development. It utilizes a continuous wave optical source with the laser intensity modulated by a frequency-swept waveform for acoustic wave generation. The small amplitude of the generated acoustic wave is significantly compensated by increased signal-to-noise ratio (several orders of magnitude) using matched-filter and pulse compression correlation processing in a manner similar to radar systems. The current study introduces the theory of a novel FD-PAR modality for ultra-sensitive characterization of functional information for breast cancer imaging. The newly developed theory of wavelength-modulated differential PA spectroscopy (WM-DPAS) detection has been introduced to address angiogenesis and hypoxia monitoring, two well-known benchmarks of breast tumor formation. Based on the WM-DPAS theory, this modality efficiently suppresses background absorptions and is expected to detect very small changes in total hemoglobin concentration and oxygenation levels, thereby identifying pre-malignant tumors before they are anatomically apparent. An experimental system design for the WM-DPAS is presented and preliminary single-ended laser experimental results were obtained and compared to a limiting case of the developed theoretical formalism.

1-J white-light continuum from 100-TW laser pulses

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

Petit, Yannick; Henin, Stefano; Bejot, Pierre

2011-01-15

We experimentally measured the supercontinuum generation using 3-J, 30-fs laser pulses and measured white-light generation at the level of 1 J. Such high energy is allowed by a strong contribution to the continuum by the photon bath, as compared to the self-guided filaments. This contribution due to the recently observed congestion of the filament number density in the beam profile at very high intensity also results in a wider broadening for positively chirped pulses rather than for negatively chirped ones, similar to broadening in hollow-core fibers.

Effects of preoperative ultrasound-guided transversus abdominis plane block on pain after laparoscopic surgery for colorectal cancer: a double-blind randomized controlled trial.

PubMed

Oh, Tak Kyu; Yim, Jiyeon; Kim, Jaehyun; Eom, Woosik; Lee, Soon Ae; Park, Sung Chan; Oh, Jae Hwan; Park, Ji Won; Park, Boram; Kim, Dae Hyun

2017-01-01

Although laparoscopic colorectal surgery decreases postoperative pain and facilitates a speedier recovery compared with laparotomy, postoperative pain at trocar insertion sites remains a clinical concern. The objective of this study was to assess the effects of a preoperative ultrasound-guided transversus abdominis plane (TAP) block on pain after laparoscopic surgery for colorectal cancer. In total, 58 patients scheduled to undergo laparoscopic surgery following a diagnosis of colorectal cancer were included in this study. The patients were randomized into TAP and control groups; the TAP group patients received a preoperative ultrasound-guided bilateral TAP block with 0.5 mL/kg of 0.25 % bupivacaine, while the control patients received the block with an equal amount of saline. Pain on coughing and at rest was assessed during postanesthetic recovery (PAR; 1 h after surgery) and on postoperative days (PODs) 1 (24 h), 2 (48 h), and 3 (72 h) by an investigator blinded to group allocations using the numeric rating scale (NRS). The primary outcome was pain on coughing on postoperative day (POD) 1. Fifty-five patients were included in the final analysis, including 28 in the TAP and 27 in the control groups. The pain intensity on coughing and at rest during PAR and on PODs 1, 2, and 3 showed no significant differences between groups. Furthermore, there was no significant difference in postoperative opioid consumption, sedation scores, nausea scores at the four time points, complication rates, and length of hospital stay between groups. In colorectal cancer patients undergoing laparoscopic colorectal surgery, a TAP block did not offer enough benefit for clinical efficacy in terms of postoperative pain or analgesic consumption.

Identification and Characterization of Fluoroquinolone Non-susceptible Streptococcus pyogenes Clones Harboring Tetracycline and Macrolide Resistance in Shanghai, China

PubMed Central

Shen, Yinfang; Cai, Jiehao; Davies, Mark R.; Zhang, Chi; Gao, Kun; Qiao, Dan; Jiang, Haoqin; Yao, Weilei; Li, Yuefang; Zeng, Mei; Chen, Mingliang

2018-01-01

Streptococcus pyogenes, also known as group A Streptococcus (GAS), is one of the top 10 infectious causes of death worldwide. Macrolide and tetracycline resistant GAS has emerged as a major health concern in China coinciding with an ongoing scarlet fever epidemic. Furthermore, increasing rates of fluoroquinolone (FQ) non-susceptibility within GAS from geographical regions outside of China has also been reported. Fluoroquinolones are the third most commonly prescribed antibiotic in China and is an therapeutic alternative for multi-drug resistant GAS. The purpose of this study was to investigate the epidemiological and molecular features of GAS fluoroquinolone (FQ) non-susceptibility in Shanghai, China. GAS (n = 2,258) recovered between 2011 and 2016 from children and adults were tested for FQ-non-susceptibility. Efflux phenotype and mutations in parC, parE, gyrA, and gyrB were investigated and genetic relationships were determined by emm typing, pulsed-field gel electrophoresis and phylogenetic analysis. The frequency of GAS FQ-non-susceptibility was 1.3% (30/2,258), with the phenotype more prevalent in GAS isolated from adults (14.3%) than from children (1.2%). Eighty percent (24/30) of FQ-non-susceptible isolates were also resistant to both macrolides (ermB) and tetracycline (tetM) including the GAS sequence types emm12, emm6, emm11, and emm1. Genomic fingerprinting analysis of the 30 isolates revealed that non-susceptibility may arise in various genetic backgrounds even within a single emm type. No efflux phenotype was observed in FQ non-susceptible isolates, and molecular analysis of the quinolone resistance-determining regions (QRDRs) identified several sequence polymorphisms in ParC and ParE, and none in GyrA and GyrB. Expansion of this analysis to 152 publically available GAS whole genome sequences from Hong Kong predicted 7.9% (12/152) of Hong Kong isolates harbored a S79F ParC mutation, of which 66.7% (8/12) were macrolide and tetracycline resistant. Phylogenetic analysis of the parC QRDR sequences suggested the possibility that FQ resistance may be acquired through inter-species lateral gene transfer. This study reports the emergence of macrolide, tetracycline, and fluoroquinolone multidrug-resistant clones across several GAS emm types including emm1 and emm12, warranting continual surveillance given the extensive use of fluoroquinolones in clinical use. PMID:29628918

Navy Tactical Applications Guide. Volume 6, Part 1. Tropics Weather Analysis and Forecast Applications.

DTIC Science & Technology

1986-08-01

the staff of the Walter A. Bohan Company is again acknowledged. Lido A. Andreoni designed the format of the publication and layout of the case studies...A. Bohan Company 1986 L THE WALTER A. BOHAN COMPANY 2026 OAKTON STREET PARK RIDGE ILLINOIS 60068 APPLIED RESEARCH IN SATELLITE METEOROLOGY AND...Walter A. Bohan. Certified Consulting Meteorologist The Walter A. B 1 ohan Company ParK Ridge. IL 60068 Robert H. Whritner, Manager Scripps

Time-resolved in vivo luminescence dosimetry for online error detection in pulsed dose-rate brachytherapy.

PubMed

Andersen, Claus E; Nielsen, Søren Kynde; Lindegaard, Jacob Christian; Tanderup, Kari

2009-11-01

The purpose of this study is to present and evaluate a dose-verification protocol for pulsed dose-rate (PDR) brachytherapy based on in vivo time-resolved (1 s time resolution) fiber-coupled luminescence dosimetry. Five cervix cancer patients undergoing PDR brachytherapy (Varian GammaMed Plus with 192Ir) were monitored. The treatments comprised from 10 to 50 pulses (1 pulse/h) delivered by intracavitary/interstitial applicators (tandem-ring systems and/or needles). For each patient, one or two dosimetry probes were placed directly in or close to the tumor region using stainless steel or titanium needles. Each dosimeter probe consisted of a small aluminum oxide crystal attached to an optical fiber cable (1 mm outer diameter) that could guide radioluminescence (RL) and optically stimulated luminescence (OSL) from the crystal to special readout instrumentation. Positioning uncertainty and hypothetical dose-delivery errors (interchanged guide tubes or applicator movements from +/-5 to +/-15 mm) were simulated in software in order to assess the ability of the system to detect errors. For three of the patients, the authors found no significant differences (P>0.01) for comparisons between in vivo measurements and calculated reference values at the level of dose per dwell position, dose per applicator, or total dose per pulse. The standard deviations of the dose per pulse were less than 3%, indicating a stable dose delivery and a highly stable geometry of applicators and dosimeter probes during the treatments. For the two other patients, the authors noted significant deviations for three individual pulses and for one dosimeter probe. These deviations could have been due to applicator movement during the treatment and one incorrectly positioned dosimeter probe, respectively. Computer simulations showed that the likelihood of detecting a pair of interchanged guide tubes increased by a factor of 10 or more for the considered patients when going from integrating to time-resolved dose verification. The likelihood of detecting a +/-15 mm displacement error increased by a factor of 1.5 or more. In vivo fiber-coupled RL/OSL dosimetry based on detectors placed in standard brachytherapy needles was demonstrated. The time-resolved dose-rate measurements were found to provide a good way to visualize the progression and stability of PDR brachytherapy dose delivery, and time-resolved dose-rate measurements provided an increased sensitivity for detection of dose-delivery errors compared with time-integrated dosimetry.

Pulse compression using a tapered microstructure optical fiber.

PubMed

Hu, Jonathan; Marks, Brian S; Menyuk, Curtis R; Kim, Jinchae; Carruthers, Thomas F; Wright, Barbara M; Taunay, Thierry F; Friebele, E J

2006-05-01

We calculate the pulse compression in a tapered microstructure optical fiber with four layers of holes. We show that the primary limitation on pulse compression is the loss due to mode leakage. As a fiber's diameter decreases due to the tapering, so does the air-hole diameter, and at a sufficiently small diameter the guided mode loss becomes unacceptably high. For the four-layer geometry we considered, a compression factor of 10 can be achieved by a pulse with an initial FWHM duration of 3 ps in a tapered fiber that is 28 m long. We find that there is little difference in the pulse compression between a linear taper profile and a Gaussian taper profile. More layers of air-holes allows the pitch to decrease considerably before losses become unacceptable, but only a moderate increase in the degree of pulse compression is obtained.

Sonothrombolysis of Intra-Catheter Aged Venous Thrombi Using Microbubble Enhancement and Guided Three Dimensional Ultrasound Pulses

PubMed Central

Kutty, Shelby; Xie, Feng; Gao, Shunji; Drvol, Lucas K; Lof, John; Fletcher, Scott E; Radio, Stanley J; Danford, David A; Hammel, James M; Porter, Thomas R

2010-01-01

Central venous and arterial catheters are a major source of thrombo-embolic disease in children. We hypothesized that guided high mechanical index (MI) impulses from diagnostic three-dimensional (3D) ultrasound during an intravenous microbubble infusion could dissolve these thrombi. An in vitro system simulating intra-catheter thrombi was created and then treated with guided high MI impulses from 3D ultrasound, utilizing low MI microbubble sensitive imaging pulse sequence schemes to detect the microbubbles (Perflutren Lipid Microsphere, Definity®, Lantheus). Ten aged thrombi over 24 hours old were tested using 3D ultrasound coupled with a continuous diluted microbubble infusion (Group A), and ten with 3D ultrasound alone (Group B). Mean thrombus age was 28.6 hours (range 26.6–30.3). Groups A exhibited a 55 ± 19 % reduction in venous thrombus size, compared to 31±10 % for Group B (p=0.008). Feasibility testing was performed in 4 pigs, establishing a model to further investigate the efficacy. Sonothrombolysis of aged intra-catheter venous thrombi can be achieved with commercially available microbubbles and guided high MI ultrasound from a diagnostic 3D transducer. PMID:20696549

A near-Infrared SETI Experiment: Alignment and Astrometric precision

NASA Astrophysics Data System (ADS)

Duenas, Andres; Maire, Jerome; Wright, Shelley; Drake, Frank D.; Marcy, Geoffrey W.; Siemion, Andrew; Stone, Remington P. S.; Tallis, Melisa; Treffers, Richard R.; Werthimer, Dan

2016-06-01

Beginning in March 2015, a Near-InfraRed Optical SETI (NIROSETI) instrument aiming to search for fast nanosecond laser pulses, has been commissioned on the Nickel 1m-telescope at Lick Observatory. The NIROSETI instrument makes use of an optical guide camera, SONY ICX694 CCD from PointGrey, to align our selected sources into two 200µm near-infrared Avalanche Photo Diodes (APD) with a field-of-view of 2.5"x2.5" each. These APD detectors operate at very fast bandwidths and are able to detect pulse widths extending down into the nanosecond range. Aligning sources onto these relatively small detectors requires characterizing the guide camera plate scale, static optical distortion solution, and relative orientation with respect to the APD detectors. We determined the guide camera plate scale as 55.9+- 2.7 milli-arcseconds/pixel and magnitude limit of 18.15mag (+1.07/-0.58) in V-band. We will present the full distortion solution of the guide camera, orientation, and our alignment method between the camera and the two APDs, and will discuss target selection within the NIROSETI observational campaign, including coordination with Breakthrough Listen.

Spatiotemporal optical pulse transformation by a resonant diffraction grating

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

Golovastikov, N. V.; Bykov, D. A., E-mail: bykovd@gmail.com; Doskolovich, L. L., E-mail: leonid@smr.ru

The diffraction of a spatiotemporal optical pulse by a resonant diffraction grating is considered. The pulse diffraction is described in terms of the signal (the spatiotemporal incident pulse envelope) passage through a linear system. An analytic approximation in the form of a rational function of two variables corresponding to the angular and spatial frequencies has been obtained for the transfer function of the system. A hyperbolic partial differential equation describing the general form of the incident pulse envelope transformation upon diffraction by a resonant diffraction grating has been derived from the transfer function. A solution of this equation has beenmore » obtained for the case of normal incidence of a pulse with a central frequency lying near the guided-mode resonance of a diffraction structure. The presented results of numerical simulations of pulse diffraction by a resonant grating show profound changes in the pulse envelope shape that closely correspond to the proposed theoretical description. The results of the paper can be applied in creating new devices for optical pulse shape transformation, in optical information processing problems, and analog optical computations.« less

On-Sky Tests of a High-Power Pulsed Laser for Sodium Laser Guide Star Adaptive Optics

NASA Astrophysics Data System (ADS)

Otarola, Angel; Hickson, Paul; Gagné, Ronald; Bo, Yong; Zuo, Junwei; Xie, Shiyong; Feng, Lu; Rochester, Simon; Budker, Dmitry; Shen, Shixia; Xue, Suijian; Min, Li; Wei, Kai; Boyer, Corinne; Ellerbroek, Brent; Hu, Jingyao; Peng, Qinjun; Xu, Zuyan

2016-03-01

We present results of on-sky tests performed in the summer of 2013 to characterize the performance of a prototype high-power pulsed laser for adaptive optics. The laser operates at a pulse repetition rate (PRR) of 600-800Hz, with a 6% duty cycle. Its coupling efficiency was found to be, in the best test case (using 18W of transmitted power), 231±14 photons s-1 sr-1 atom-1 W-1 m2 when circular polarization was employed and 167±17 photons s-1 sr-1 atom-1 W-1 m2 with linear polarization. No improvement was seen when D2b repumping was used, but this is likely due to the relatively large laser guide star (LGS) diameter, typically 10 arcsec or more, which resulted in low irradiance levels. Strong relaxation oscillations were present in the laser output, which have the effect of reducing the coupling efficiency. To better understand the results, a physical modeling was performed using the measured pulse profiles and parameters specific to these tests. The model results, for a 10 arcsec angular size LGS spot, agree well with the observations. When extrapolating the physical model for a sub-arcsecond angular size LGS (typical of what is needed for a successful astronomical guide star), the model predicts that this laser would have a coupling efficiency of 130 photons s-1 sr-1 atom-1 W-1 m2, using circular polarization and D2b repumping, for a LGS diameter of 0.6 arcsec Full Width at Half Maximum (FWHM), and free of relaxation oscillations in the 589 nm laser light.

Molecular Mechanisms of Fluoroquinolone Resistance in Pseudomonas aeruginosa Isolates from Cystic Fibrosis Patients

PubMed Central

Jalal, Shah; Ciofu, Oana; Høiby, Niels; Gotoh, Naomasa; Wretlind, Bengt

2000-01-01

Twenty P. aeruginosa isolates were collected from six cystic fibrosis (CF) patients, aged 27 to 33, in 1994 (9 isolates) and 1997 (11 isolates) at the CF Center, Copenhagen, Denmark, and were typed by pulse-field gel electrophoresis (PFGE) or ribotyping. Five of the patients had isolates with the same PFGE or ribotyping patterns in 1997 as in 1994, and ciprofloxacin had a two- to fourfold higher MIC for the isolates collected in 1997 than those from 1994. Genomic DNA was amplified for gyrA, parC, mexR, and nfxB by PCR and sequenced. Eleven isolates had mutations in gyrA, seven isolates had mutations at codon 83 (Thr to Ile), and four isolates had mutations at codon 87 (Asp to Asn or Tyr). Sixteen isolates had mutations in nfxB at codon 82 (Arg to Leu). Increased amounts of OprN were found in six isolates and OprJ in eight isolates as determined by immunoblotting. No isolates had mutations in parC or mexR. Six isolates had mutations in efflux pumps without gyrA mutations. The average number of mutations was higher in isolates from 1997 than in those from 1994. The results also suggested that efflux resistance mechanisms are more common in isolates from CF patients than in strains from urine and wounds from non-CF patients, in which mutations in gyrA and parC dominate (S. Jalal and B. Wretlind, Microb. Drug Resist. 4:257–261, 1998). PMID:10681343

Nd:YAG Pulsed Laser based flaw imaging techniques for noncontact NDE of an aluminum plate

NASA Astrophysics Data System (ADS)

Park, Woong-Ki; Lee, Changgil; Park, Seunghee

2012-04-01

Recently, the longitudinal, shear and surface waves have been very widely used as a kind of ultrasonic wave exploration methods to identify internal defects of metallic structures. The ultrasonic wave-based non-destructive testing (NDT) is one of main non-destructive inspection techniques for a health assessment about nuclear power plant, aircraft, ships, and/or automobile manufacturing. In this study, a noncontact pulsed laser-based flaw imaging NDT technique is implemented to detect the damage of a plate-like structure and to identify the location of the damage. To achieve this goal, the Nd:YAG pulsed laser equipment is used to generate a guided wave and scans a specific area to find damage location. The Nd: YAG pulsed laser is used to generate Lamb wave and piezoelectric sensors are installed to measure structural responses. Ann aluminum plate is investigated to verify the effectiveness and the robustness of the proposed NDT approach. A notch is a target to detect, which is inflicted on the surface of an aluminum plate. The damagesensitive features are extracted by comparing the time of flight of the guided wave obtained from an acoustic emission (AE) sensor and make use of the flaw imaging techniques of the aluminum plate.

Application of MR-guided focused pulsed ultrasound for destroying clots in vitro using thrombolytic drugs

NASA Astrophysics Data System (ADS)

Hadjisavvas, V.; Ioannides, K.; Damianou, C.

2011-09-01

In this paper an MR-guided focused pulsed ultrasound system for the treatment of stroke using thrombolytic drugs in a model in vitro is presented. A single element spherically focused transducer of 5 cm diameter; focusing at 10 cm and operating at 0.5 MHz or 1 MHz was used. The transducer was mounted in an MR compatible robot. The artery was modelled using a silicone tube. Tissue was modelled using polyaclylimide gel. Coagulated blood was used to model thrombus. A thermocouple was placed in the thrombus in order to measure the thrombus temperature. The effect of power, beam, and frequency was investigated. The goal was to maintain a temperature increase of less than 1 °C during the application of pulse ultrasound (called safe temperature). With the application of ultrasound alone there was no notable destruction of the thrombus. With the combination of ultrasound and thrombolytic drugs destruction occurred after 60 mins of pulse exposure (PRF = 1 s, duty factor = 10%, and with thrombus placed at 1 cm deep in the tissue). This simple in vitro model was proven very successful for evaluating MRgFUS as a modality for treating stroke. In the future we plan to apply this treatment protocol in live animals and humans.

Post-filament self-trapping of ultrashort laser pulses.

PubMed

Mitrofanov, A V; Voronin, A A; Sidorov-Biryukov, D A; Andriukaitis, G; Flöry, T; Pugžlys, A; Fedotov, A B; Mikhailova, J M; Panchenko, V Ya; Baltuška, A; Zheltikov, A M

2014-08-15

Laser filamentation is understood to be self-channeling of intense ultrashort laser pulses achieved when the self-focusing because of the Kerr nonlinearity is balanced by ionization-induced defocusing. Here, we show that, right behind the ionized region of a laser filament, ultrashort laser pulses can couple into a much longer light channel, where a stable self-guiding spatial mode is sustained by the saturable self-focusing nonlinearity. In the limiting regime of negligibly low ionization, this post-filamentation beam dynamics converges to a large-scale beam self-trapping scenario known since the pioneering work on saturable self-focusing nonlinearities.

Computer-Aided Structural Engineering (CASE) Project: Investigation and Design of U-Frame Structures Using Program CUFRBC. Volume C. User’s Guide for Channels

DTIC Science & Technology

1990-05-01

1988) or ACI 318-83 (1983). Actual calculations for section strength are made using subroutines taken from the CASE program CSTR (Hamby and Price...validity of the design of their par- ticular structure. Thus, it is essential that the user of the program under- stand the design algorithm included...modes. However, several restrictions were placed on the design mode to avoid unnecessary com- plications of the design algorithm for cases rarely

Position paper on digital communication in dentistry.

PubMed

Chambers, David W

2012-01-01

Digital communication offers advantages and challenges to dental practice. As dentistry becomes comfortable with this technology, it is essential that commercial and other values not be accepted on a par with professional ones and that the traditional dentist-patient relationship not be compromised by inserting third parties that introduce nonprofessional standards. The Officers and Regents of the American College of Dentist have prepared this background and position paper as a guide to the ethical use of digital communication in dental practice.

Communication: XFAIMS—eXternal Field Ab Initio Multiple Spawning for electron-nuclear dynamics triggered by short laser pulses

DOE PAGES

Mignolet, Benoit; Curchod, Basile F. E.; Martinez, Todd J.

2016-11-17

Attoscience is an emerging field where attosecond pulses or few cycle IR pulses are used to pump and probe the correlated electron-nuclear motion of molecules. We present the trajectory-guided eXternal Field Ab Initio Multiple Spawning (XFAIMS) method that models such experiments “on-the-fly,” from laser pulse excitation to fragmentation or nonadiabatic relaxation to the ground electronic state. For the photoexcitation of the LiH molecule, we show that XFAIMS gives results in close agreement with numerically exact quantum dynamics simulations, both for atto- and femtosecond laser pulses. As a result, we then show the ability of XFAIMS to model the dynamics inmore » polyatomic molecules by studying the effect of nuclear motion on the photoexcitation of a sulfine (H 2CSO).« less

Circularly polarized attosecond pulse generation and applications to ultrafast magnetism

NASA Astrophysics Data System (ADS)

Bandrauk, André D.; Guo, Jing; Yuan, Kai-Jun

2017-12-01

Attosecond science is a growing new field of research and potential applications which relies on the development of attosecond light sources. Achievements in the generation and application of attosecond pulses enable to investigate electron dynamics in the nonlinear nonperturbative regime of laser-matter interactions on the electron’s natural time scale, the attosecond. In this review, we describe the generation of circularly polarized attosecond pulses and their applications to induce attosecond magnetic fields, new tools for ultrafast magnetism. Simulations are performed on aligned one-electron molecular ions by using nonperturbative nonlinear solutions of the time-dependent Schrödinger equation. We discuss how bichromatic circularly polarized laser pulses with co-rotating or counter-rotating components induce electron-parent ion recollisions, thus producing circularly polarized high-order harmonic generation, the source of circularly polarized attosecond pulses. Ultrafast quantum electron currents created by the generated attosecond pulses give rise to attosecond magnetic field pulses. The results provide a guiding principle for producing circularly polarized attosecond pulses and ultrafast magnetic fields in complex molecular systems for future research in ultrafast magneto-optics.

Metal wires for terahertz wave guiding.

PubMed

Wang, Kanglin; Mittleman, Daniel M

2004-11-18

Sources and systems for far-infrared or terahertz (1 THz = 10(12) Hz) radiation have received extensive attention in recent years, with applications in sensing, imaging and spectroscopy. Terahertz radiation bridges the gap between the microwave and optical regimes, and offers significant scientific and technological potential in many fields. However, waveguiding in this intermediate spectral region still remains a challenge. Neither conventional metal waveguides for microwave radiation, nor dielectric fibres for visible and near-infrared radiation can be used to guide terahertz waves over a long distance, owing to the high loss from the finite conductivity of metals or the high absorption coefficient of dielectric materials in this spectral range. Furthermore, the extensive use of broadband pulses in the terahertz regime imposes an additional constraint of low dispersion, which is necessary for compatibility with spectroscopic applications. Here we show how a simple waveguide, namely a bare metal wire, can be used to transport terahertz pulses with virtually no dispersion, low attenuation, and with remarkable structural simplicity. As an example of this new waveguiding structure, we demonstrate an endoscope for terahertz pulses.

Physical exercise, fitness and dietary pattern and their relationship with circadian blood pressure pattern, augmentation index and endothelial dysfunction biological markers: EVIDENT study protocol

PubMed Central

2010-01-01

Background Healthy lifestyles may help to delay arterial aging. The purpose of this study is to analyze the relationship of physical activity and dietary pattern to the circadian pattern of blood pressure, central and peripheral blood pressure, pulse wave velocity, carotid intima-media thickness and biological markers of endothelial dysfunction in active and sedentary individuals without arteriosclerotic disease. Methods/Design Design: A cross-sectional multicenter study with six research groups. Subjects: From subjects of the PEPAF project cohort, in which 1,163 who were sedentary became active, 1,942 were sedentary and 2,346 were active. By stratified random sampling, 1,500 subjects will be included, 250 in each group. Primary measurements: We will evaluate height, weight, abdominal circumference, clinical and ambulatory blood pressure with the Radial Pulse Wave Acquisition Device (BPro), central blood pressure and augmentation index with Pulse Wave Application Software (A-Pulse) and SphymgoCor System Px (Pulse Wave Analysis), pulse wave velocity (PWV) with SphymgoCor System Px (Pulse Wave Velocity), nutritional pattern with a food intake frequency questionnaire, physical activity with the 7-day PAR questionnaire and accelerometer (Actigraph GT3X), physical fitness with the cycle ergometer (PWC-170), carotid intima-media thickness by ultrasound (Micromax), and endothelial dysfunction biological markers (endoglin and osteoprotegerin). Discussion Determining that sustained physical activity and the change from sedentary to active as well as a healthy diet improve circadian pattern, arterial elasticity and carotid intima-media thickness may help to propose lifestyle intervention programs. These interventions could improve the cardiovascular risk profile in some parameters not routinely assessed with traditional risk scales. From the results of this study, interventional approaches could be obtained to delay vascular aging that combine physical exercise and diet. Trial Registration Clinical Trials.gov Identifier: NCT01083082 PMID:20459634

Wavepacket dynamics of a Rydberg atom monitored by a pair of time-delayed laser pulses

NASA Astrophysics Data System (ADS)

Xin, PeiPei; Cheng, Hong; Zhang, ShanShan; Wang, HanMu; Liu, HongPing

2018-02-01

We have investigated the Rydberg state population of an argon atom by an intense laser pulse and its wavepacket dynamics monitored by another successive laser pulse in the tunneling regime. A wavepacket comprising a superposition of close high-lying Rydberg states is irradiated by a multicycle laser pulse, where the sub-wave components in the wavepacket have fixed relative phases. A time-delayed second laser pulse is employed to apply on the excited Rydberg atom. If the time is properly chosen, one of the sub-wave components will be guided towards the ionization area while the rest remains intact. By means of this pump-probe technique, we could control and monitor the Rydberg wavepacket dynamics and reveal some interesting phenomenon such as the survival rate of individual Rydberg states related to the classical orbital period of electron.

Self-compression of spatially limited laser pulses in a system of coupled light-guides

NASA Astrophysics Data System (ADS)

Balakin, A. A.; Litvak, A. G.; Mironov, V. A.; Skobelev, S. A.

2018-04-01

The self-action features of wave packets propagating in a 2D system of equidistantly arranged fibers are studied analytically and numerically on the basis of the discrete nonlinear Schrödinger equation. Self-consistent equations for the characteristic scales of a Gaussian wave packet are derived on the basis of the variational approach, which are proved numerically for powers P < 10 P_cr , slightly exceeding the critical one for self-focusing. At higher powers, the wave beams become filamented, and their amplitude is limited due to the nonlinear breaking of the interaction between neighboring light-guides. This makes it impossible to collect a powerful wave beam in a single light-guide. Variational analysis shows the possibility of the adiabatic self-compression of soliton-like laser pulses in the process of 3D self-focusing on the central light-guide. However, further increase of the field amplitude during self-compression leads to the development of longitudinal modulation instability and the formation of a set of light bullets in the central fiber. In the regime of hollow wave beams, filamentation instability becomes predominant. As a result, it becomes possible to form a set of light bullets in optical fibers located on the ring.

High-frequency guided ultrasonic waves for hidden defect detection in multi-layered aircraft structures.

PubMed

Masserey, Bernard; Raemy, Christian; Fromme, Paul

2014-09-01

Aerospace structures often contain multi-layered metallic components where hidden defects such as fatigue cracks and localized disbonds can develop, necessitating non-destructive testing. Employing standard wedge transducers, high frequency guided ultrasonic waves that penetrate through the complete thickness were generated in a model structure consisting of two adhesively bonded aluminium plates. Interference occurs between the wave modes during propagation along the structure, resulting in a frequency dependent variation of the energy through the thickness with distance. The wave propagation along the specimen was measured experimentally using a laser interferometer. Good agreement with theoretical predictions and two-dimensional finite element simulations was found. Significant propagation distance with a strong, non-dispersive main wave pulse was achieved. The interaction of the high frequency guided ultrasonic waves with small notches in the aluminium layer facing the sealant and on the bottom surface of the multilayer structure was investigated. Standard pulse-echo measurements were conducted to verify the detection sensitivity and the influence of the stand-off distance predicted from the finite element simulations. The results demonstrated the potential of high frequency guided waves for hidden defect detection at critical and difficult to access locations in aerospace structures from a stand-off distance. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Self-action of Bessel wave packets in a system of coupled light guides and formation of light bullets

NASA Astrophysics Data System (ADS)

Balakin, A. A.; Mironov, V. A.; Skobelev, S. A.

2017-01-01

The self-action of two-dimensional and three-dimensional Bessel wave packets in a system of coupled light guides is considered using the discrete nonlinear Schrödinger equation. The features of the self-action of such wave fields are related to their initial strong spatial inhomogeneity. The numerical simulation shows that for the field amplitude exceeding a critical value, the development of an instability typical of a medium with the cubic nonlinearity is observed. Various regimes are studied: the self-channeling of a wave beam in one light guide at powers not strongly exceeding a critical value, the formation of the "kaleidoscopic" picture of a wave packet during the propagation of higher-power radiation along a stratified medium, the formation of light bullets during competition between self-focusing and modulation instabilities in the case of three-dimensional wave packets, etc. In the problem of laser pulse shortening, the situation is considered when the wave-field stratification in the transverse direction dominates. This process is accompanied by the self-compression of laser pulses in well enough separated light guides. The efficiency of conversion of the initial Bessel field distribution to two flying parallel light bullets is about 50%.

Self-action of Bessel wave packets in a system of coupled light guides and formation of light bullets

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

Balakin, A. A., E-mail: balakin.alexey@yandex.ru; Mironov, V. A.; Skobelev, S. A., E-mail: sk.sa1981@gmail.com

The self-action of two-dimensional and three-dimensional Bessel wave packets in a system of coupled light guides is considered using the discrete nonlinear Schrödinger equation. The features of the self-action of such wave fields are related to their initial strong spatial inhomogeneity. The numerical simulation shows that for the field amplitude exceeding a critical value, the development of an instability typical of a medium with the cubic nonlinearity is observed. Various regimes are studied: the self-channeling of a wave beam in one light guide at powers not strongly exceeding a critical value, the formation of the “kaleidoscopic” picture of a wavemore » packet during the propagation of higher-power radiation along a stratified medium, the formation of light bullets during competition between self-focusing and modulation instabilities in the case of three-dimensional wave packets, etc. In the problem of laser pulse shortening, the situation is considered when the wave-field stratification in the transverse direction dominates. This process is accompanied by the self-compression of laser pulses in well enough separated light guides. The efficiency of conversion of the initial Bessel field distribution to two flying parallel light bullets is about 50%.« less

Large scale Tesla coil guided discharges initiated by femtosecond laser filamentation in air

NASA Astrophysics Data System (ADS)

Arantchouk, L.; Point, G.; Brelet, Y.; Prade, B.; Carbonnel, J.; André, Y.-B.; Mysyrowicz, A.; Houard, A.

2014-07-01

The guiding of meter scale electric discharges produced in air by a Tesla coil is realized in laboratory using a focused terawatt laser pulse undergoing filamentation. The influence of the focus position, the laser arrival time, or the gap length is studied to determine the best conditions for efficient laser guiding. Discharge parameters such as delay, jitter, and resistance are characterized. An increase of the discharge length by a factor 5 has been achieved with the laser filaments, corresponding to a mean breakdown field of 2 kV/cm for a 1.8 m gap length. Consecutive guided discharges at a repetition rate of 10 Hz are also reported.

Periodontal treatment with the frequency-doubled Alexandrite laser in dogs

NASA Astrophysics Data System (ADS)

Rechmann, Peter; Hennig, Thomas; Reichart, Peter

2000-03-01

While earlier periodontal investigations have proved the frequency doubled Alexandrite laser to eliminate efficiently and selectively dental calculus as well as bacteria the aim of this study was to demonstrate the safety of this laser for removal of dental calculus with respect to the dental pulp. Four adult Labrador dogs were treated with a frequency doubled Alexandrite laser (laboratory prototype, q-switched, fiber guided, wavelength 377 nm, pulse duration 1 microsecond, pulse repetition rate 70 Hz, water cooling) to remove dental calculus. After performing a modified Widman flap procedure the buccal surface of nine teeth in the lower and upper right jaw were irradiated for four minutes per tooth. Three different laser fluences up to four times higher than the fluence required for calculus removal were used (1.5, 3 and 6 J/cm2). At three other sites of the right jaw deep cavities were prepared with a dental drill and filled with compomere material (DyractR, Dentsply, Germany) to serve as a positive control with regard to possible pulpal reactions. The corresponding teeth of the lower and upper left jaw served as controls. Animals were sacrificed one day, one week, four weeks and six weeks after treatment. Teeth were separated, fixed in formalin and decalcified. After embedding and sectioning the histological sections were stained and investigated by a totally blinded investigator (P.A.R). Histological investigations revealed that irradiation with the frequency doubled Alexandrite laser for periodontal treatment with fluences of 1.5 J/cm2 -- those fluences necessary for the selective removal of dental calculus and microbial plaque -- had no adverse side effects to the pulpal tissues. Moreover this pulpal safety study demonstrated that even applying fluences two or four times higher than those suggested for calculus removal do not lead to observable changes or alterations in the odontoblast cell layer or the pulpal tissues. No inflammatory reactions and no differences between irradiated and control teeth occurred, while the positive controls showed reactions in the odontoblast cell layer and the connective pulpal tissue.

Development of a fiber-guided laser ultrasonic system resilient to high temperature and gamma radiation for nuclear power plant pipe monitoring

NASA Astrophysics Data System (ADS)

Yang, Jinyeol; Lee, Hyeonseok; Lim, Hyung Jin; Kim, Nakhyeon; Yeo, Hwasoo; Sohn, Hoon

2013-08-01

This study develops an embeddable optical fiber-guided laser ultrasonic system for structural health monitoring (SHM) of pipelines exposed to high temperature and gamma radiation inside nuclear power plants (NPPs). Recently, noncontact laser ultrasonics is gaining popularity among the SHM community because of its advantageous characteristics such as (a) scanning capability, (b) immunity against electromagnetic interference (EMI) and (c) applicability to high-temperature surfaces. However, its application to NPP pipelines has been hampered because pipes inside NPPs are often covered by insulators and/or target surfaces are not easily accessible. To overcome this problem, this study designs embeddable optical fibers and fixtures so that laser beams used for ultrasonic inspection can be transmitted between the laser sources and the target pipe. For guided-wave generation, an Nd:Yag pulsed laser coupled with an optical fiber is used. A high-power pulsed laser beam is guided through the optical fiber onto a target structure. Based on the principle of laser interferometry, the corresponding response is measured using a different type of laser beam guided by another optical fiber. All devices are especially designed to sustain high temperature and gamma radiation. The robustness/resilience of the proposed measurement system installed on a stainless steel pipe specimen has been experimentally verified by exposing the specimen to high temperature of up to 350 °C and optical fibers to gamma radiation of up to 125 kGy (20 kGy h-1).

A Guide to Making an Audio Tape.

ERIC Educational Resources Information Center

Jobe, Holly; Cannon, Glenn

This brief introduction to the use of audiotape recorders in educational settings provides basic information on operational procedures and recording techniques for voice, music, dubbing, and pulsing. Audiotape editing and splicing are also explained. (RAO)

Factors influencing performance of health workers in the management of seriously sick children at a Kenyan tertiary hospital--participatory action research.

PubMed

Irimu, Grace W; Greene, Alexandra; Gathara, David; Kihara, Harrison; Maina, Christopher; Mbori-Ngacha, Dorothy; Zurovac, Dejan; Migiro, Santau; English, Mike

2014-02-07

Implementation of World Health Organization case management guidelines for serious childhood illnesses remains a challenge in hospitals in low-income countries. Facilitators of and barriers to implementation of locally adapted clinical practice guidelines (CPGs) have not been explored. This ethnographic study based on the theory of participatory action research (PAR) was conducted in Kenyatta National Hospital, Kenya's largest teaching hospital. The primary intervention consisted of dissemination of locally adapted CPGs. The PRECEDE-PROCEED health education model was used as the conceptual framework to guide and examine further reinforcement activities to improve the uptake of the CPGs. Activities focussed on introduction of routine clinical audits and tailored educational sessions. Data were collected by a participant observer who also facilitated the PAR over an eighteen-month period. Naturalistic inquiry was utilized to obtain information from all hospital staff encountered while theoretical sampling allowed in-depth exploration of emerging issues. Data were analysed using interpretive description. Relevance of the CPGs to routine work and emergence of a champion of change facilitated uptake of best-practices. Mobilization of basic resources was relatively easily undertaken while activities that required real intellectual and professional engagement of the senior staff were a challenge. Accomplishments of the PAR were largely with the passive rather than active involvement of the hospital management. Barriers to implementation of best-practices included i) mismatch between the hospital's vision and reality, ii) poor communication, iii) lack of objective mechanisms for monitoring and evaluating quality of clinical care, iv) limited capacity for planning strategic change, v) limited management skills to introduce and manage change, vi) hierarchical relationships, and vii) inadequate adaptation of the interventions to the local context. Educational interventions, often regarded as 'quick-fixes' to improve care in low-income countries, may be necessary but are unlikely to be sufficient to deliver improved services. We propose that an understanding of organizational issues that influence the behaviour of individual health professionals should guide and inform the implementation of best-practices.

Blocking and guiding adult sea lamprey with pulsed direct current from vertical electrodes

USGS Publications Warehouse

Johnson, Nicholas S.; Thompson, Henry T.; Holbrook, Christopher M.; Tix, John A.

2014-01-01

Controlling the invasion front of aquatic nuisance species is of high importance to resource managers. We tested the hypothesis that adult sea lamprey (Petromyzon marinus), a destructive invasive species in the Laurentian Great Lakes, would exhibit behavioral avoidance to dual-frequency pulsed direct current generated by vertical electrodes and that the electric field would not injure or kill sea lamprey or non-target fish. Laboratory and in-stream experiments demonstrated that the electric field blocked sea lamprey migration and directed sea lamprey into traps. Rainbow trout (Oncorhynchus mykiss) and white sucker (Catostomus commersoni), species that migrate sympatrically with sea lamprey, avoided the electric field and had minimal injuries when subjected to it. Vertical electrodes are advantageous for fish guidance because (1) the electric field produced varies minimally with depth, (2) the electric field is not grounded, reducing power consumption to where portable and remote deployments powered by solar, wind, hydro, or a small generator are feasible, and (3) vertical electrodes can be quickly deployed without significant stream modification allowing rapid responses to new invasions. Similar dual-frequency pulsed direct current fields produced from vertical electrodes may be advantageous for blocking or trapping other invasive fish or for guiding valued fish around dams.

THz-driven zero-slippage IFEL scheme for phase space manipulation

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

Curry, E.; Fabbri, S.; Musumeci, P.

In this paper, we describe an inverse free electron laser (IFEL) interaction driven by a near single-cycle THz pulse that is group velocity-matched to an electron bunch inside a waveguide, allowing for a sustained interaction in a magnetic undulator. We discuss the application of this guided-THz IFEL technique for compression of a relativistic electron bunch and synchronization with the external laser pulse used to generate the THz pulse via optical rectification, as well as a laser-driven THz streaking diagnostic with the potential for femtosecond scale temporal resolution. Initial measurements of the THz waveform via an electro-optic sampling based technique confirm the predicted reduction of the group velocity, using a curved parallel plate waveguide, as a function of the varying aperture size of the guide. We also present the design of a proof-of-principle experiment based on the bunch parameters available at the UCLA PEGASUS laboratory. With amore » $$10\\,\\mathrm{MV}\\,{{\\rm{m}}}^{-1}$$ THz peak field, our simulation model predicts compression of a $$6\\,\\mathrm{MeV}$$ $$100\\,\\mathrm{fs}$$ electron beam by nearly an order of magnitude and a significant reduction of its initial timing jitter.« less

THz-driven zero-slippage IFEL scheme for phase space manipulation

DOE PAGES

Curry, E.; Fabbri, S.; Musumeci, P.; ...

2016-11-24

In this paper, we describe an inverse free electron laser (IFEL) interaction driven by a near single-cycle THz pulse that is group velocity-matched to an electron bunch inside a waveguide, allowing for a sustained interaction in a magnetic undulator. We discuss the application of this guided-THz IFEL technique for compression of a relativistic electron bunch and synchronization with the external laser pulse used to generate the THz pulse via optical rectification, as well as a laser-driven THz streaking diagnostic with the potential for femtosecond scale temporal resolution. Initial measurements of the THz waveform via an electro-optic sampling based technique confirm the predicted reduction of the group velocity, using a curved parallel plate waveguide, as a function of the varying aperture size of the guide. We also present the design of a proof-of-principle experiment based on the bunch parameters available at the UCLA PEGASUS laboratory. With amore » $$10\\,\\mathrm{MV}\\,{{\\rm{m}}}^{-1}$$ THz peak field, our simulation model predicts compression of a $$6\\,\\mathrm{MeV}$$ $$100\\,\\mathrm{fs}$$ electron beam by nearly an order of magnitude and a significant reduction of its initial timing jitter.« less

Polarization-dependent intermodal four-wave mixing in a birefringent multimode photonic crystal fiber.

PubMed

Yuan, Jinhui; Kang, Zhe; Li, Feng; Zhou, Guiyao; Sang, Xinzhu; Wu, Qiang; Yan, Binbin; Zhou, Xian; Zhong, Kangping; Wang, Liang; Wang, Kuiru; Yu, Chongxiu; Lu, Chao; Tam, Hwa Yaw; Wai, P K A

2017-05-01

In this Letter, polarization-dependent intermodal four-wave mixing (FWM) is demonstrated experimentally in a birefringent multimode photonic crystal fiber (BM-PCF) designed and fabricated in-house. Femtosecond pump pulses at wavelengths ∼800  nm polarized along one of the principal axes of the BM-PCF are coupled into a normal dispersion region away from the zero-dispersion wavelengths of the fundamental guided mode of the BM-PCF. Anti-Stokes and Stokes waves are generated in the 2nd guided mode at visible and near-infrared wavelengths, respectively. For pump pulses at an average input power of 500 mW polarized along the slow axis, the conversion efficiencies η_as and η_s of the anti-Stokes and Stokes waves generated at wavelengths 579.7 and 1290.4 nm are 19% and 14%, respectively. For pump pulses polarized along the fast axis, the corresponding η_as and η_s at 530.4 and 1627 nm are 23% and 18%, respectively. We also observed that fiber bending and intermodal walk-off have a small effect on the polarization-dependent intermodal FWM-based frequency conversion process.

Development of a fluorimeter using laser-induced single-shot fluorescence lifetime spectroscopy

NASA Astrophysics Data System (ADS)

Eisum, Niels H.; Lynggaard-Jensen, Anders

1990-08-01

The developed laboratory prototype fluorimeter is the first step to a new in-situ instrument, and is based on a pulsed nitrogen laser (pumping a color dye laser and the laserbeam passing through a frequency doubler) with a pulse width less than 1 nsec. With such a short excitation pulse it is possible to measure the exponential decay of the fluorescence from the aromatic compounds and thus determine the fluorescence lifetime-curves, which are typically in the region of 5-40 nsec. The emitted fluorescence is collected simultaneously in 35 channels in the wavelength region 250-600 nm. If the fluorescence falls within the transmission areas of the interference filters in each channel the light will be collected by a plastic light guide (doped PMMA) in the actual channel and transmitted to the channels photo multiplier tube (PMT). (The use of the plastic light guide improves the sensitivity). The signal from the PMT is passed on to a 200 MHz 8-bit flash AID-converter connected to a local memory. From this local memory the digital lifetime curves from each channel are transmitted to a computer for presentation of the 3-dimensional spectrum. This spectrum has been obtained with a single laser shot.

Nonlinear compression of temporal solitons in an optical waveguide via inverse engineering

NASA Astrophysics Data System (ADS)

Paul, Koushik; Sarma, Amarendra K.

2018-03-01

We propose a novel method based on the so-called shortcut-to-adiabatic passage techniques to achieve fast compression of temporal solitons in a nonlinear waveguide. We demonstrate that soliton compression could be achieved, in principle, at an arbitrarily small distance by inverse-engineering the pulse width and the nonlinearity of the medium. The proposed scheme could possibly be exploited for various short-distance communication protocols and may be even in nonlinear guided wave-optics devices and generation of ultrashort soliton pulses.

High-resolution imaging and target designation through clouds or smoke

DOEpatents

Perry, Michael D.

2003-01-01

A method and system of combining gated intensifiers and advances in solid-state, short-pulse laser technology, compact systems capable of producing high resolution (i.e., approximately less than 20 centimeters) optical images through a scattering medium such as dense clouds, fog, smoke, etc. may be achieved from air or ground based platforms. Laser target designation through a scattering medium is also enabled by utilizing a short pulse illumination laser and a relatively minor change to the detectors on laser guided munitions.

Serial removal of caries lesions from tooth occlusal surfaces using near-IR image-guided IR laser ablation

NASA Astrophysics Data System (ADS)

Chan, Kenneth H.; Tom, Henry; Darling, Cynthia L.; Fried, Daniel

2015-02-01

Previous studies have established that caries lesions can be imaged with high contrast without the interference of stains at near-IR wavelengths greater than 1300-nm. It has been demonstrated that computer controlled laser scanning systems utilizing IR lasers operating at high pulse repetition rates can be used for serial imaging and selective removal of caries lesions. In this study, we report our progress towards the development of algorithms for generating rasterized ablation maps from near-IR reflectance images for the removal of natural lesions from tooth occlusal surfaces. An InGaAs camera and a filtered tungsten-halogen lamp producing near-IR light in the range of 1500-1700-nm were used to collect crosspolarization reflectance images of tooth occlusal surfaces. A CO2 laser operating at a wavelength of 9.3- μm with a pulse duration of 10-15-μs was used for image-guided ablation.

Enhanced hole boring with two-color relativistic laser pulses in the fast ignition scheme

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

Yu, Changhai; Tian, Ye; Li, Wentao

A scheme of using two-color laser pulses for hole boring into overdense plasma as well as energy transfer into electron and ion beams has been studied using particle-in-cell simulations. Following an ultra-short ultra-intense hole-boring laser pulse with a short central wavelength in extreme ultra-violet range, the main infrared driving laser pulse can be guided in the hollow channel preformed by the former laser and propagate much deeper into an overdense plasma, as compared to the case using the infrared laser only. In addition to efficiently transferring the main driving laser energy into energetic electrons and ions generation deep inside themore » overdense plasma, the ion beam divergence can be greatly reduced. The results might be beneficial for the fast ignition concept of inertial confinement fusion.« less

Plasmid partition system of the P1par family from the pWR100 virulence plasmid of Shigella flexneri.

PubMed

Sergueev, Kirill; Dabrazhynetskaya, Alena; Austin, Stuart

2005-05-01

P1par family members promote the active segregation of a variety of plasmids and plasmid prophages in gram-negative bacteria. Each has genes for ParA and ParB proteins, followed by a parS partition site. The large virulence plasmid pWR100 of Shigella flexneri contains a new P1par family member: pWR100par. Although typical parA and parB genes are present, the putative pWR100parS site is atypical in sequence and organization. However, pWR100parS promoted accurate plasmid partition in Escherichia coli when the pWR100 Par proteins were supplied. Unique BoxB hexamer motifs within parS define species specificities among previously described family members. Although substantially different from P1parS from the P1 plasmid prophage of E. coli, pWR100parS has the same BoxB sequence. As predicted, the species specificity of the two types proved identical. They also shared partition-mediated incompatibility, consistent with the proposed mechanistic link between incompatibility and species specificity. Among several informative sequence differences between pWR100parS and P1parS is the presence of a 21-bp insert at the center of the pWR100parS site. Deletion of this insert left much of the parS activity intact. Tolerance of central inserts with integral numbers of helical DNA turns reflects the critical topology of these sites, which are bent by binding the host IHF protein.

Modeling of intense pulsed ion beam heated masked targets for extreme materials characterization

DOE PAGES

Barnard, John J.; Schenkel, Thomas

2017-11-15

Intense, pulsed ion beams locally heat materials and deliver dense electronic excitations that can induce material modifications and phase transitions. Material properties can potentially be stabilized by rapid quenching. Pulsed ion beams with pulse lengths of order ns have recently become available for materials processing. Here, we optimize mask geometries for local modification of materials by intense ion pulses. The goal is to rapidly excite targets volumetrically to the point where a phase transition or local lattice reconstruction is induced followed by rapid cooling that stabilizes desired material's properties fast enough before the target is altered or damaged by, e.g.,more » hydrodynamic expansion. By using a mask, the longitudinal dimension can be large compared to the transverse dimension, allowing the possibility of rapid transverse cooling. We performed HYDRA simulations that calculate peak temperatures for a series of excitation conditions and cooling rates of silicon targets with micro-structured masks and compare these to a simple analytical model. In conclusion, the model gives scaling laws that can guide the design of targets over a wide range of pulsed ion beam parameters.« less

Nonlinear Dichroism in Back-to-Back Double Ionization of He by an Intense Elliptically Polarized Few-Cycle Extreme Ultraviolet Pulse.

PubMed

Ngoko Djiokap, J M; Manakov, N L; Meremianin, A V; Hu, S X; Madsen, L B; Starace, Anthony F

2014-11-28

Control of double ionization of He by means of the polarization and carrier-envelope phase (CEP) of an intense, few-cycle extreme ultraviolet (XUV) pulse is demonstrated numerically by solving the six-dimensional two-electron, time-dependent Schrödinger equation for He interacting with an elliptically polarized XUV pulse. Guided by perturbation theory (PT), we predict the existence of a nonlinear dichroic effect (∝I^{3/2}) that is sensitive to the CEP, ellipticity, peak intensity I, and temporal duration of the pulse. This dichroic effect (i.e., the difference of the two-electron angular distributions for opposite helicities of the ionizing XUV pulse) originates from interference of first- and second-order PT amplitudes, allowing one to probe and control S- and D-wave channels of the two-electron continuum. We show that the back-to-back in-plane geometry with unequal energy sharing is an ideal one for observing this dichroic effect that occurs only for an elliptically polarized, few-cycle attosecond pulse.

Initial state-specific photodissociation dynamics of pyrrole via 1 π σ ∗/ S 0 conical intersection initiated with optimally controlled UV-laser pulses

NASA Astrophysics Data System (ADS)

Nandipati, K. R.; Kanakati, Arun Kumar; Singh, H.; Lan, Z.; Mahapatra, S.

2017-09-01

Optimal initiation of quantum dynamics of N-H photodissociation of pyrrole on the S0-1πσ∗(1A2) coupled electronic states by UV-laser pulses in an effort to guide the subsequent dynamics to dissociation limits is studied theoretically. Specifically, the task of designing optimal laser pulses that act on initial vibrational states of the system for an effective UV-photodissociation is considered by employing optimal control theory. The associated control mechanism(s) for the initial state dependent photodissociation dynamics of pyrrole in the presence of control pulses is examined and discussed in detail. The initial conditions determine implicitly the variation in the dissociation probabilities for the two channels, upon interaction with the field. The optimal pulse corresponds to the objective fixed as maximization of overall reactive flux subject to constraints of reasonable fluence and quantum dynamics. The simple optimal pulses obtained by the use of genetic algorithm based optimization are worth an experimental implementation given the experimental relevance of πσ∗-photochemistry in recent times.

Control of ultrafast pulses in a hydrogen-filled hollow-core photonic-crystal fiber by Raman coherence

NASA Astrophysics Data System (ADS)

Belli, F.; Abdolvand, A.; Travers, J. C.; Russell, P. St. J.

2018-01-01

We present the results of an experimental and numerical investigation into temporally nonlocal coherent interactions between ultrashort pulses, mediated by Raman coherence, in a gas-filled kagome-style hollow-core photonic-crystal fiber. A pump pulse first sets up the Raman coherence, creating a refractive index spatiotemporal grating in the gas that travels at the group velocity of the pump pulse. Varying the arrival time of a second, probe, pulse allows a high degree of control over its evolution as it propagates along the fiber through the grating. Of particular interest are soliton-driven effects such as self-compression and dispersive wave (DW) emission. In the experiments reported, a DW is emitted at ˜300 nm and exhibits a wiggling effect, with its central frequency oscillating periodically with pump-probe delay. The results demonstrate that a strong Raman coherence, created in a broadband guiding gas-filled kagome photonic-crystal fiber, can be used to control the nonlinear dynamics of ultrashort probe pulses, even in difficult-to-access spectral regions such as the deep and vacuum ultraviolet.

Modeling of intense pulsed ion beam heated masked targets for extreme materials characterization

NASA Astrophysics Data System (ADS)

Barnard, John J.; Schenkel, Thomas

2017-11-01

Intense, pulsed ion beams locally heat materials and deliver dense electronic excitations that can induce material modifications and phase transitions. Material properties can potentially be stabilized by rapid quenching. Pulsed ion beams with pulse lengths of order ns have recently become available for materials processing. Here, we optimize mask geometries for local modification of materials by intense ion pulses. The goal is to rapidly excite targets volumetrically to the point where a phase transition or local lattice reconstruction is induced followed by rapid cooling that stabilizes desired material's properties fast enough before the target is altered or damaged by, e.g., hydrodynamic expansion. By using a mask, the longitudinal dimension can be large compared to the transverse dimension, allowing the possibility of rapid transverse cooling. We performed HYDRA simulations that calculate peak temperatures for a series of excitation conditions and cooling rates of silicon targets with micro-structured masks and compare these to a simple analytical model. The model gives scaling laws that can guide the design of targets over a wide range of pulsed ion beam parameters.

Image-guided removal of occlusal caries lesions with a λ= 9.3-µm CO2 laser using near-IR transillumination

PubMed Central

Chung, Leon C.; Tom, Henry; Chan, Kenneth H.; Simon, Jacob C.; Fried, Daniel; Darling, Cynthia L.

2015-01-01

Previous studies have shown that near-IR transillumination is well suited for imaging deep occlusal lesions. The purpose of this study was to determine if near-IR images can be used to guide a CO2 laser for the selective removal of natural occlusal lesions on extracted teeth. Near-IR occlusal transillumination images of extracted human teeth with natural occlusal caries lesions were acquired using an InGaAs camera and near-IR light at wavelengths from 1290 to 1470-nm from a filtered tungsten halogen source. A CO2 laser operating at 9.3-µm with a pulse duration of 10–15-µs and a pulse repetition rate of 100–300-Hz was used for caries removal. Optical Coherence tomography was used to confirm lesion presence and serial scans were used to assess selective removal. Teeth were also sectioned for histological examination using polarized light microscopy. This study suggests that near-infrared transillumination is a promising method for the image guided laser ablation of occlusal caries lesions but the use of serial near-IR transillumination imaging for monitoring lesion removal was limited. PMID:25914498

Image-guided removal of occlusal caries lesions with a λ= 9.3-μm CO2 laser using near-IR transillumination

NASA Astrophysics Data System (ADS)

Chung, Leon C.; Tom, Henry; Chan, Kenneth H.; Simon, Jacob C.; Fried, Daniel; Darling, Cynthia L.

2015-02-01

Previous studies have shown that near-IR transillumination is well suited for imaging deep occlusal lesions. The purpose of this study was to determine if near-IR images can be used to guide a CO2 laser for the selective removal of natural occlusal lesions on extracted teeth. Near-IR occlusal transillumination images of extracted human teeth with natural occlusal caries lesions were acquired using an InGaAs camera and near-IR light at wavelengths from 1290 to 1470-nm from a filtered tungsten halogen source. A CO2 laser operating at 9.3-μm with a pulse duration of 10-15-μs and a pulse repetition rate of 100-300-Hz was used for caries removal. Optical Coherence tomography was used to confirm lesion presence and serial scans were used to assess selective removal. Teeth were also sectioned for histological examination using polarized light microscopy. This study suggests that near-infrared transillumination is a promising method for the image guided laser ablation of occlusal caries lesions but the use of serial near-IR transillumination imaging for monitoring lesion removal was limited.

Experimental generation of discrete ultraviolet wavelength by cascaded intermodal four-wave mixing in a multimode photonic crystal fiber.

PubMed

Yuan, Jinhui; Kang, Zhe; Li, Feng; Zhang, Xianting; Mei, Chao; Zhou, Guiyao; Sang, Xinzhu; Wu, Qiang; Yan, Binbin; Zhou, Xian; Zhong, Kangping; Wang, Kuiru; Yu, Chongxiu; Farrell, Gerald; Lu, Chao; Tam, Hwa Yaw; Wai, P K A

2017-09-15

In this Letter, we demonstrate experimentally for the first time, to the best of our knowledge, discrete ultraviolet (UV) wavelength generation by cascaded intermodal FWM when femtosecond pump pulses at 800 nm are launched into the deeply normal dispersion region of the fundamental guided mode of a multimode photonic crystal fiber (MPCF). For pump pulses at average input powers of P av =450, 550, and 650 mW, the first anti-Stokes waves are generated at the visible wavelength of 538.1 nm through intermodal phase matching between the fundamental and second-order guided mode of the MPCF. The first anti-Stokes waves generated then serve as the secondary pump for the next intermodal FWM process. The second anti-Stokes waves in the form of the third-order guided mode are generated at the UV wavelength of 375.8 nm. The maximum output power is above 10 mW for P av =650  mW. We also confirm that the influences of fiber bending and intermodal walk-offs on the cascaded intermodal FWM-based frequency conversion process are negligible.

Surface-Wave Pulse Routing around Sharp Right Angles

NASA Astrophysics Data System (ADS)

Gao, Z.; Xu, H.; Gao, F.; Zhang, Y.; Luo, Y.; Zhang, B.

2018-04-01

Surface-plasmon polaritons (SPPs), or localized electromagnetic surface waves propagating on a metal-dielectric interface, are deemed promising information carriers for future subwavelength terahertz and optical photonic circuitry. However, surface waves fundamentally suffer from scattering loss when encountering sharp corners in routing and interconnection of photonic signals. Previous approaches enabling scattering-free surface-wave guidance around sharp corners are limited to either volumetric waveguide environments or extremely narrow bandwidth, being unable to guide a surface-wave pulse (SPP wave packet) on an on-chip platform. Here, in a surface-wave band-gap crystal implemented on a single metal surface, we demonstrate in time-domain routing a surface-wave pulse around multiple sharp right angles without perceptible scattering. Our work not only offers a solution to on-chip surface-wave pulse routing along an arbitrary path, but it also provides spatiotemporal information on the interplay between surface-wave pulses and sharp corners, both of which are desirable in developing high-performance large-scale integrated photonic circuits.

Longitudinal Waves Drive the Solar Cycle

NASA Astrophysics Data System (ADS)

Wagner, Orvin

2000-05-01

In Physics Essays 12: 3-10 I explain the placement of the planets in terms of low velocity waves emitted by the sun. Evidence for the wave pulse generated near the center of the sun is indicated by the initial high latitude sunspots observed on the butterfly diagram. The wave pulse carries charge with it as observed for similar waves in plants (W-waves). For the first half cycle negative charge is carried to the surface of the sun where much of the wave pulse radiates a wave crest into space while the charge slowly redistributes itself. Meanwhile the next wave pulse carrying excess positive charge moves outward. Rotating charge determines the polarity of the sun's magnetic poles so they reverse as the pulse moves outward. The wave pulse, which interacts strongly with force fields, is guided by centripetal force and gravity so that the pulse comes out near the sun's equator. W-waves produce an automatic return wave in the vacuum so that standing waves are produced in the space around the sun providing a template for the formation and stabilization planets. W-waves are hypothesized to provide self organization for both the universe and life. See the

Influence of Ankle Active Dorsiflexion Movement Guided by Inspiration on the Venous Return From the Lower Limbs: A Prospective Study.

PubMed

Pi, Hongying; Ku, Hong'an; Zhao, Ting; Wang, Jie; Fu, Yicheng

2018-04-01

Active ankle movement is recommended intervention for preventing deep vein thrombosis effectively and easily by promoting venous return from the lower limbs. The active ankle dorsiflexion and plantar flexion movement guided by deep breathing is considered the most effective method, although outstanding problems remain, including low patient compliance and difficult motion essentials. The aims of this study were to compare the influence of different ankle active movements on venous return from the lower limbs and to suggest the optimal movement for preventing deep venous thrombosis in the lower limbs. A self-controlled study on 130 subjects was undertaken. The femoral venous hemodynamics of the left femoral vein and changes in pulse oxygen saturation and heart rate were compared among the three states of quiescent, active ankle 30° dorsiflexion movement, and active ankle 30° dorsiflexion with active plantar 45° flexion movement. The immediate master rates of the two ankle movements were examined before the study. The femoral venous hemodynamics of the left femoral vein were significantly higher in both movement states compared with the quiescent state. Moreover, no significant difference was found among the three states in terms of pulse oxygen saturation and heart rate. The immediate master rate was significantly higher in the active ankle 30° dorsiflexion movement than in the active ankle 30° dorsiflexion and active plantar 45° flexion movement. Therefore, active ankle 30° dorsiflexion movement guided by inspiration was found in this study to increase femoral venous hemodynamics, which heightened the immediate master rate but had no obvious influence on pulse oxygen saturation and heart rate. Active ankle 30° dorsiflexion movement guided by inspiration effectively promotes venous return from the lower limbs and is a better method to prevent deep vein thrombosis of the lower limbs.

Community Evaluation of the National Diabetes Education Program's Diabetes HealthSense Website.

PubMed

Sadler, Michele DeBarthe; Saperstein, Sandra L; Carpenter, Carrie; Devchand, Roshni; Tuncer, Diane; O'Brian, Catherine; Nicols, Christina; Gallivan, Joanne

2017-10-01

Purpose The purpose of this study was to assess the impact of Diabetes HealthSense on knowledge, attitudes, and behavior changes that prevent, delay, or manage diabetes among people at risk (PAR) for diabetes and people with diabetes (PWD). Methods Using a 2-group pretest-posttest design, 15 community sites were randomly assigned to either an intervention or comparison group. Intervention participants attended a group education session with a diabetes educator, followed by 4 weeks of independent use of the Diabetes HealthSense website. The comparison group received no intervention. A total of 311 adults (n = 135 intervention, n = 176 comparison) completed both a pretest and posttest. Outcome measures examined changes in self-reported knowledge, self-efficacy, and behaviors that support diabetes prevention or management. Results Statistically significant within-group pretest to posttest changes were found for almost all outcome measures in the intervention group, with no significant changes in the comparison group. Significant between-group differences were also found for almost all outcome measures at posttest, with the intervention group having more positive outcomes than the comparison group. Conclusions Patient referral to online tools is considered one key component of initial and ongoing diabetes self-management education and support (DSME/S) and is recommended as a way to enhance and extend the reach of in-person diabetes education. Positive outcomes were found for PWD/PAR who used Diabetes HealthSense following a guided education session. Study results suggested that with guided exploration, Diabetes HealthSense provided a valuable tool for educators to use with patients to support and extend the reach of DSME/S.

Protease-activated receptor (PAR)-2 is required for PAR-1 signalling in pulmonary fibrosis

PubMed Central

Lin, Cong; von der Thüsen, Jan; Daalhuisen, Joost; ten Brink, Marieke; Crestani, Bruno; van der Poll, Tom; Borensztajn, Keren; Spek, C Arnold

2015-01-01

Idiopathic pulmonary fibrosis is the most devastating diffuse fibrosing lung disease of unknown aetiology. Compelling evidence suggests that both protease-activated receptor (PAR)-1 and PAR-2 participate in the development of pulmonary fibrosis. Previous studies have shown that bleomycin-induced lung fibrosis is diminished in both PAR-1 and PAR-2 deficient mice. We thus have been suggested that combined inactivation of PAR-1 and PAR-2 would be more effective in blocking pulmonary fibrosis. Human and murine fibroblasts were stimulated with PAR-1 and PAR-2 agonists in the absence or presence of specific PAR-1 or PAR-2 antagonists after which fibrotic markers like collagen and smooth muscle actin were analysed by Western blot. Pulmonary fibrosis was induced by intranasal instillation of bleomycin into wild-type and PAR-2 deficient mice with or without a specific PAR-1 antagonist (P1pal-12). Fibrosis was assessed by hydroxyproline quantification and (immuno)histochemical analysis. We show that specific PAR-1 and/or PAR-2 activating proteases induce fibroblast migration, differentiation and extracellular matrix production. Interestingly, however, combined activation of PAR-1 and PAR-2 did not show any additive effects on these pro-fibrotic responses. Strikingly, PAR-2 deficiency as well as pharmacological PAR-1 inhibition reduced bleomycin-induced pulmonary fibrosis to a similar extent. PAR-1 inhibition in PAR-2 deficient mice did not further diminish bleomycin-induced pulmonary fibrosis. Finally, we show that the PAR-1-dependent pro-fibrotic responses are inhibited by the PAR-2 specific antagonist. Targeting PAR-1 and PAR-2 simultaneously is not superior to targeting either receptor alone in bleomycin-induced pulmonary fibrosis. We postulate that the pro-fibrotic effects of PAR-1 require the presence of PAR-2. PMID:25689283

Experiences of Familial Acceptance–Rejection Among Transwomen of Color

PubMed Central

Koken, Juline A.; Bimbi, David S.; Parsons, Jeffrey T.

2010-01-01

Because of the stigma associated with transgenderism, many transwomen (biological males who identify as female or transgender) experience rejection or abuse at the hands of their parents and primary caregivers as children and adolescents. The Parental Acceptance–Rejection (PAR) theory indicates that a child's experience of rejection may have a significant impact on their adult lives. The purpose of this study was to conduct a qualitative analysis of adult transwomen of color's experiences with caregivers, guided by PAR theory. Twenty transwomen of color completed semi-structured interviews exploring the reaction of their parents and primary caregivers to their gender. While many participants reported that at least one parent or close family member responded with warmth and acceptance, the majority confronted hostility and aggression; reports of neglect and undifferentiated rejection were also common. Many transwomen were forced out of their homes as adolescents or chose to leave, increasing their risk of homelessness, poverty, and associated negative sequelae. Future research is needed to explore how families come to terms with having a transgender child and how best to promote acceptance of such children. PMID:20001144

Microcomponents manufacturing for precise devices by copper vapor laser

NASA Astrophysics Data System (ADS)

Gorny, Sergey; Nikonchuk, Michail O.; Polyakov, Igor V.

2001-06-01

This paper presents investigation results of drilling of metal microcomponents by copper vapor laser. The laser consists of master oscillator - spatial filter - amplifier system, electronics switching with digital control of laser pulse repetition rate and quantity of pulses, x-y stage with computer control system. Mass of metal, removed by one laser pulse, is measured and defined by means of diameter and depth of holes. Interaction of next pulses on drilled material is discussed. The difference between light absorption and metal evaporation processes is considered for drilling and cutting. Efficiency of drilling is estimated by ratio of evaporation heat and used laser energy. Maximum efficiency of steel cutting is calculated with experimental data of drilling. Applications of copper vapor laser for manufacturing is illustrated by such microcomponents as pin guide plate for printers, stents for cardio surgery, encoded disks for security systems and multiple slit masks for spectrophotometers.

Electromagnetically driven radiative shocks and their measurements

NASA Astrophysics Data System (ADS)

Kondo, K.; Nakajima, M.; Kawamura, T.; Horioka, K.

2006-06-01

Experimental results on a generation of strong shocks in a compact pulse power device are reported. To make a strong and plain shock wave, electrodes are tapered and an acrylic guiding tube is located on the top of the electrodes. It drives a quasi-one-dimensional strong shock in the guiding tube. When the front speed is more than the critical speed Drad, an interesting structure is confirmed at the shock front, which indicate a phenomenon proceeded by the radiative transport.

Plates-formes de microscopie et fluorescence par resonance de plasmons de surface appliquees a l'imagerie cellulaire

NASA Astrophysics Data System (ADS)

Chabot, Vincent

L'elaboration de nouveaux medicaments repose sur les etudes pharmacologiques, dont le role est d'identifier de nouveaux composes actifs ou de nouvelles cibles pharmacologiques agissant entre autres au niveau cellulaire. Recemment, la detection basee sur la resonance des plasmons de surface (SPR) a ete appliquee a l'etude de reponses cellulaires. Cette methode de detection, permettant d'observer des variations d'indice de refraction associes a de faibles changements de masse a la surface d'un metal, a l'avantage de permettre l'etude d'une population de cellules vivantes en temps reel, sans necessiter l'introduction d'agents de marquage. Pour effectuer la detection au niveau de cellules individuelles, on peut employer la microscopie SPR, qui consiste a localiser spatialement la detection par un systeme d'imagerie. Cependant, la detection basee sur la SPR est une mesure sans marquage et les signaux mesures sont attribues a une reponse moyennee des differentes sources cellulaires. Afin de mieux comprendre et identifier les composantes cellulaires generant le signal mesure en SPR, il est pertinent de combiner la microscopie SPR avec une modalite complementaire, soit l'imagerie de fluorescence. C'est dans cette problematique que s'insere ce projet de these, consistant a concevoir deux plates-formes distinctes de microscopie SPR et de fluorescence optimisees pour l'etude cellulaire, de sorte a evaluer les possibilites d'integration de ces deux modalites en un seul systeme. Des substrats adaptes pour chaque plate-forme ont ete concus et realises. Ces substrats employaient une couche d'argent passivee par l'ajout d'une mince couche d'or. La stabilite et la biocompatibilite des substrats ont ete validees pour l'etude cellulaire. Deux configurations permettant d'ameliorer la sensibilite en sondant les cellules plus profondement ont ete evaluees, soit l'emploi de plasmons de surface a longue portee et de guides d'onde a gaine metallique. La sensibilite accrue de ces configurations a aussi ete demontree pour un usage en biodetection cellulaire. Une plate-forme permettant de mesurer la spectroscopie SPR simultanement avec l'acquisition d'images de fluorescence a ete realisee. Cette plate-forme a ensuite ete validee par l'etude de reponses cellulaires suite a une stimulation pharmacologique. Puis, un systeme base sur la microscopie SPR a ete concu et caracterise. Son emploi pour l'etude de reponses au niveau de cellules individuelles a ete demontre. Finalement, les forces et faiblesses des substrats et des plates-formes realisees au cours de la these ont ete evaluees. Des possibilites d'amelioration sont mises de l'avant et l'integration des modalites de microscopie SPR et de fluorescence suite aux travaux de la these est discutee. Les realisations au cours de cette etude ont donc permis d'identifier les composantes cellulaires impliquees dans la generation du signal mesure en biodetection SPR. Mots-cles : Resonance des plasmons de surface, microscopie SPR, plasmons de surface a longue portee LRSPR, guide d'onde a gaine metallique MCWG, fluorescence exaltee par plasmons de surface SPEF, biodetection cellulaire, imagerie SPR.

20 mJ, 1 ps Yb:YAG Thin-disk Regenerative Amplifier

PubMed Central

Alismail, Ayman; Wang, Haochuan; Brons, Jonathan; Fattahi, Hanieh

2017-01-01

This is a report on a 100 W, 20 mJ, 1 ps Yb:YAG thin-disk regenerative amplifier. A homemade Yb:YAG thin-disk, Kerr-lens mode-locked oscillator with turn-key performance and microjoule-level pulse energy is used to seed the regenerative chirped-pulse amplifier. The amplifier is placed in airtight housing. It operates at room temperature and exhibits stable operation at a 5 kHz repetition rate, with a pulse-to-pulse stability less than 1%. By employing a 1.5 mm-thick beta barium borate crystal, the frequency of the laser output is doubled to 515 nm, with an average power of 70 W, which corresponds to an optical-to-optical efficiency of 70%. This superior performance makes the system an attractive pump source for optical parametric chirped-pulse amplifiers in the near-infrared and mid-infrared spectral range. Combining the turn-key performance and the superior stability of the regenerative amplifier, the system facilitates the generation of a broadband, CEP-stable seed. Providing the seed and pump of the optical parametric chirped-pulse amplification (OPCPA) from one laser source eliminates the demand of active temporal synchronization between these pulses. This work presents a detailed guide to set up and operate a Yb:YAG thin-disk regenerative amplifier, based on chirped-pulse amplification (CPA), as a pump source for an optical parametric chirped-pulse amplifier. PMID:28745636

Spatiotemporal evolution of cavitation dynamics exhibited by flowing microbubbles during ultrasound exposure.

PubMed

Choi, James J; Coussios, Constantin-C

2012-11-01

Ultrasound and microbubble-based therapies utilize cavitation to generate bioeffects, yet cavitation dynamics during individual pulses and across consecutive pulses remain poorly understood under physiologically relevant flow conditions. SonoVue(®) microbubbles were made to flow (fluid velocity: 10-40 mm/s) through a vessel in a tissue-mimicking material and were exposed to ultrasound [frequency: 0.5 MHz, peak-rarefactional pressure (PRP): 150-1200 kPa, pulse length: 1-100,000 cycles, pulse repetition frequency (PRF): 1-50 Hz, number of pulses: 10-250]. Radiated emissions were captured on a linear array, and passive acoustic mapping was used to spatiotemporally resolve cavitation events. At low PRPs, stable cavitation was maintained throughout several pulses, thus generating a steady rise in energy with low upstream spatial bias within the focal volume. At high PRPs, inertial cavitation was concentrated in the first 6.3 ± 1.3 ms of a pulse, followed by an energy reduction and high upstream bias. Multiple pulses at PRFs below a flow-dependent critical rate (PRF(crit)) produced predictable and consistent cavitation dynamics. Above the PRF(crit), energy generated was unpredictable and spatially biased. In conclusion, key parameters in microbubble-seeded flow conditions were matched with specific types, magnitudes, distributions, and durations of cavitation; this may help in understanding empirically observed in vivo phenomena and guide future pulse sequence designs.

Outcomes of microscope-integrated intraoperative optical coherence tomography-guided center-sparing internal limiting membrane peeling for myopic traction maculopathy: a novel technique.

PubMed

Kumar, Atul; Ravani, Raghav; Mehta, Aditi; Simakurthy, Sriram; Dhull, Chirakshi

2017-07-04

To evaluate the outcomes of pars plana vitrectomy (PPV) with microscope-integrated intraoperative optical coherence tomography (I-OCT)-guided traction removal and center-sparing internal limiting membrane (cs-ILM) peeling. Nine eyes with myopic traction maculopathy as diagnosed on SD-OCT underwent PPV with I-OCT-guided cs-ILM peeling and were evaluated prospectively for resolution of central macular thickness (CMT) and improvement in best-corrected visual acuity (BCVA), and complications, if any, were noted. All patients were followed up for more than 9 months. Resolution of the macular retinoschisis was seen in all nine eyes on SD-OCT. At 36 weeks, there was a significant improvement in mean BCVA from the preoperative BCVA (P = 0.0089) along with a reduction in the CMT from 569.77 ± 263.19 to 166.0 ± 43.91 um (P = 0.0039). None of the eyes showed worsening of BCVA or development of full-thickness macular hole in the intraoperative or follow-up period. PPV with I-OCT-guided cs-ILM peeling helps in complete removal of traction, resolution of retinoschisis and good functional recovery with low intraoperative and postoperative complications.

Protease-activated receptor (PAR)-2 is required for PAR-1 signalling in pulmonary fibrosis.

PubMed

Lin, Cong; von der Thüsen, Jan; Daalhuisen, Joost; ten Brink, Marieke; Crestani, Bruno; van der Poll, Tom; Borensztajn, Keren; Spek, C Arnold

2015-06-01

Idiopathic pulmonary fibrosis is the most devastating diffuse fibrosing lung disease of unknown aetiology. Compelling evidence suggests that both protease-activated receptor (PAR)-1 and PAR-2 participate in the development of pulmonary fibrosis. Previous studies have shown that bleomycin-induced lung fibrosis is diminished in both PAR-1 and PAR-2 deficient mice. We thus have been suggested that combined inactivation of PAR-1 and PAR-2 would be more effective in blocking pulmonary fibrosis. Human and murine fibroblasts were stimulated with PAR-1 and PAR-2 agonists in the absence or presence of specific PAR-1 or PAR-2 antagonists after which fibrotic markers like collagen and smooth muscle actin were analysed by Western blot. Pulmonary fibrosis was induced by intranasal instillation of bleomycin into wild-type and PAR-2 deficient mice with or without a specific PAR-1 antagonist (P1pal-12). Fibrosis was assessed by hydroxyproline quantification and (immuno)histochemical analysis. We show that specific PAR-1 and/or PAR-2 activating proteases induce fibroblast migration, differentiation and extracellular matrix production. Interestingly, however, combined activation of PAR-1 and PAR-2 did not show any additive effects on these pro-fibrotic responses. Strikingly, PAR-2 deficiency as well as pharmacological PAR-1 inhibition reduced bleomycin-induced pulmonary fibrosis to a similar extent. PAR-1 inhibition in PAR-2 deficient mice did not further diminish bleomycin-induced pulmonary fibrosis. Finally, we show that the PAR-1-dependent pro-fibrotic responses are inhibited by the PAR-2 specific antagonist. Targeting PAR-1 and PAR-2 simultaneously is not superior to targeting either receptor alone in bleomycin-induced pulmonary fibrosis. We postulate that the pro-fibrotic effects of PAR-1 require the presence of PAR-2. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Shoulder pain in primary care: diagnostic accuracy of clinical examination tests for non-traumatic acromioclavicular joint pain

PubMed Central

2013-01-01

Background Despite numerous methodological flaws in previous study designs and the lack of validation in primary care populations, clinical tests for identifying acromioclavicular joint (ACJ) pain are widely utilised without concern for such issues. The aim of this study was to estimate the diagnostic accuracy of traditional ACJ tests and to compare their accuracy with other clinical examination features for identifying a predominant ACJ pain source in a primary care cohort. Methods Consecutive patients with shoulder pain were recruited prospectively from primary health care clinics. Following a standardised clinical examination and diagnostic injection into the subacromial bursa, all participants received a fluoroscopically guided diagnostic block of 1% lidocaine hydrochloride (XylocaineTM) into the ACJ. Diagnostic accuracy statistics including sensitivity, specificity, predictive values, positive and negative likelihood ratios (LR+ and LR-) were calculated for traditional ACJ tests (Active Compression/O’Brien’s test, cross-body adduction, localised ACJ tenderness and Hawkins-Kennedy test), and for individual and combinations of clinical examination variables that were associated with a positive anaesthetic response (PAR) (P≤0.05) defined as 80% or more reduction in post-injection pain intensity during provocative clinical tests. Results Twenty two of 153 participants (14%) reported an 80% PAR. None of the traditional ACJ tests were associated with an 80% PAR (P<0.05) and combinations of traditional tests were not able to discriminate between a PAR and a negative anaesthetic response (AUC 0.507; 95% CI: 0.366, 0.647; P>0.05). Five clinical examination variables (repetitive mechanism of pain onset, no referred pain below the elbow, thickened or swollen ACJ, no symptom provocation during passive glenohumeral abduction and external rotation) were associated with an 80% PAR (P<0.05) and demonstrated an ability to accurately discriminate between an PAR and NAR (AUC 0.791; 95% CI 0.702, 0.880; P<0.001). Less than two positive clinical features resulted in 96% sensitivity (95% CI 0.78, 0.99) and a LR- 0.09 (95% CI 0.02, 0.41) and four positive clinical features resulted in 95% specificity (95% CI 0.90, 0.98) and a LR+ of 4.98 (95% CI 1.69, 13.84). Conclusions In this cohort of primary care patients with predominantly subacute or chronic ACJ pain of non-traumatic onset, traditional ACJ tests were of limited diagnostic value. Combinations of other history and physical examination findings were able to more accurately identify injection-confirmed ACJ pain in this cohort. PMID:23634871

A study on laser-based ultrasonic technique by the use of guided wave tomographic imaging

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

Park, Junpil, E-mail: jpp@pusan.ac.kr; Lim, Juyoung, E-mail: jpp@pusan.ac.kr; Cho, Younho

2015-03-31

Guided wave tests are impractical for investigating specimens with limited accessibility and coarse surfaces or geometrically complicated features. A non-contact setup with a laser ultrasonic transmitter and receiver is the classic attractive for guided wave inspection. The present work was done to develop a non-contact guided-wave tomography technique by laser ultrasonic technique in a plate-like structure. A method for Lam wave generation and detection in an aluminum plate with a pulse laser ultrasonic transmitter and a Michelson interferometer receiver has been developed. In the images obtained by laser scanning, the defect shape and area showed good agreement with the actualmore » defect. The proposed approach can be used as a non-contact-based online inspection and monitoring technique.« less

ARGOS - the Laser Star Adaptive Optics for LBT

NASA Astrophysics Data System (ADS)

Rabien, S.; Barl, L.; Beckmann, U.; Blümchen, T.; Bonaglia, M.; Borelli, J. L.; Brynnel, J.; Busoni, L.; Carbonaro, L.; Conot, C.; Davies, R.; Deysenroth, M.; Durney, O.; Elberich, M.; Esposito, S.; Gasho, V.; Gässler, W.; Gemperlein, H.; Genzel, R.; Green, R.; Haug, M.; Lloyd Hart, M.; Hubbard, P.; Kanneganti, S.; Kulas, M.; Noenickx, J.; Peter, D.; Quirrenbach, A.; Rademacher, M.; Rix, H. W.; Salinari, P.; Schwab, C.; Storm, J.; Strüder, L.; Thiel, M.; Weigelt, G.; Ziegleder, J.; Orban de Xivry, G.

2011-09-01

We will present the design and status of ARGOS - the Laser Guide Star adaptive optics facility for the Large Binocular Telescope. By projecting a constellation of multiple laser guide stars above each of the 8.4m primary mirrors of the LBT, ARGOS in its ground layer mode will enable a wide field adaptive optics correction for multi object spectroscopy. ARGOS implements high power pulsed green lasers and makes use of Rayleigh scattering for the guide star creation. The geometric relations of this setup in guide star height vs. primary diameter are quite comparable to an ELT with sodium guide stars. The use of LBT's adaptive secondary mirror, gated wavefront sensors, a prime focus calibration system and the laser constellation shows several aspects that may be used as pathfinding technology for the planned ELTs. In already planned upgrade steps with a hybrid Sodium-Rayleigh combination ARGOS will enable MCAO and MOAO implementations at LBT allowing unique astronomical observations.

High-resolution TALIF measurements of atomic oxygen: determination of gas temperature and collisional broadening coefficients

NASA Astrophysics Data System (ADS)

Booth, Jean-Paul; Marinov, Daniil; Guaitella, Olivier; Drag, Cyril; Engeln, Richard; Golda, Judith; Schultz-von der Gathern, Volker

2016-09-01

Two-photon Absorption Laser-Induced Fluorescence (TALIF) is a well-established technique to measure relative (and with appropriate calibration techniques, absolute) densities of atoms in plasmas and flames. The excitation line profiles can provide additional information, but this is usually overlooked due to the mediocre spectral resolution of commercial pulsed dye laser systems. We have investigated O-atom TALIF excitation line profiles using a house-built narrow line-width pulsed UV laser system, based on pulsed Ti:Sa ring laser seeded by a cw infrared diode laser. The observed Doppler profiles allow unambiguous measurement of gas temperature with high precision in O2 and CO2 DC glow discharges. Sub-Doppler measurements, performed by reflecting the laser beam back through excitation zone, allow the pressure-broadened line shapes to be observed, both in a pure O2 DC discharge (up to 10 Torr pressure) and in an atmospheric pressure RF plasma jet in He/O2. Pressure broadening coefficients of the 3p3PJ state of O were determined for O2 and He bath gases, and were found to be an order of magnitude bigger than that predicted from the measured quenching rate. Work performed in the LABEX Plas@par project, with financial state aid (ANR-11-IDEX-0004-02 and ANR-13-BS09-0019).

The Role of Pulses in the Dietary Management of Diabetes.

PubMed

Ramdath, Dan; Renwick, Simone; Duncan, Alison M

2016-08-01

Pulses are highly nutritious foods that are included as part of Canada's Food Guide to promote healthful eating, and they have established health benefits that can contribute to the dietary management of diabetes. A review of studies that have examined the effects of pulse consumption on health outcomes, integral to the management of diabetes, provides credible evidence for improvements in glycemic control, reduction of blood lipids and regulation of body weight. Results from acute feeding trials suggest that postprandial blood glucose response is significantly attenuated by a single pulse serving of between three-quarters and 1 cup. At lower doses, pulses attenuate postprandial blood glucose response more than similar amounts of starchy foods. Long-term pulse consumption of 5 cups per week appears to result consistently in improvements in glycemic control. There is high-quality evidence that supports a role for pulse consumption in the reduction of risk for cardiovascular disease; this provides a sound rationale for the regular incorporation of pulses at about two-thirds of a cup daily in the management of hyperlipidemia in persons with type 2 diabetes. Pulse consumption can contribute to improving satiety, reducing food intake and regulating body weight, which can reduce obesity risk and, in turn, improve diabetes management. Collectively, available evidence provides very good support for a role of regular pulse consumption in the prevention and management of diabetes. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Expression of protease-activated receptor (PAR)-2, but not other PARs, is regulated by inflammatory cytokines in rat astrocytes.

PubMed

Sokolova, Elena; Aleshin, Stepan; Reiser, Georg

2012-02-01

Protease-activated receptors (PARs) are widely expressed in the central nervous system (CNS) and are believed to play an important role in normal brain functioning as well as in development of various inflammatory and neurodegenerative disorders. Pathological conditions cause altered expression of PARs in brain cells and therefore altered responsiveness to PAR activation. The exact mechanisms of regulation of PAR expression are not well studied. Here, we evaluated in rat astrocytes the influence of LPS, pro-inflammatory cytokines TNFα and IL-1β and continuous PAR activation by PAR agonists on the expression levels of PARs. These stimuli are important in inflammatory and neurological disorders, where their levels are increased. We report that LPS as well as cytokines TNFα and IL-1β affected only the PAR-2 level, but their effects were opposite. LPS and TNFα increased the functional expression of PAR-2, whereas IL-1β down-regulated the functional response of PAR-2. Agonists of PAR-1 specifically increased mRNA level of PAR-2, but not protein level. Transcript levels of other PARs were not changed after PAR-1 activation. Stimulation of the cells with PAR-2 or PAR-4 agonists did not alter PAR levels. We found that up-regulation of PAR-2 is dependent on PKC activity, mostly via its Ca²⁺-sensitive isoforms. Two transcription factors, NFκB and AP-1, are involved in up-regulation of PAR-2. These findings provide new information about the regulation of expression of PAR subtypes in brain cells. This is of importance for targeting PARs, especially PAR-2, for the treatment of CNS disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

Enhanced Ultrafast Nonlinear Optics With Microstructure Fibers And Photonic Crystals

DTIC Science & Technology

2004-07-01

NANOHOLES FREQUENCY-TUNABLE ANTI-STOKES LINE EMISSION BY EIGENMODES OF A BIREFRINGENT MICROSTRUCTURE FIBER GENERATION OF FEMTOSECOND ANTI-STOKES PULSES...laser technologies, and ultrafast photonics. ANTI-STOKES GENERATION IN GUIDED MODES OF PHOTONIC-CRYSTAL FIBERS MODIFIED WITH AN ARRAY OF NANOHOLES

The Object Coordination Class Applied to Wave Pulses: Analyzing Student Reasoning in Wave Physics.

ERIC Educational Resources Information Center

Wittmann, Michael C.

2002-01-01

Analyzes student responses to interview and written questions on wave physics using diSessa and Sherin's coordination class model which suggests that student use of specific reasoning resources is guided by possibly unconscious cues. (Author/MM)

Relationship between objectively measured physical activity and vascular structure and function in adults.

PubMed

Gomez-Marcos, Manuel A; Recio-Rodríguez, José I; Patino-Alonso, Maria C; Agudo-Conde, Cristina; Lasaosa-Medina, Lourdes; Rodriguez-Sanchez, Emiliano; Maderuelo-Fernandez, José A; García-Ortiz, Luis

2014-06-01

To analyze the relationship between regular physical activity, as assessed by accelerometer and 7-day physical activity recall (PAR) with vascular structure and function based on carotid intima-media thickness, pulse wave velocity, central and peripheral augmentation index and the ambulatory arterial stiffness index in adults. This study analyzed 263 subjects who were included in the EVIDENT study (mean age 55.85 ± 12.21 years; 59.30% female). Physical activity was assessed during 7 days using the Actigraph GT3X accelerometer (counts/minute) and 7-day PAR (metabolic equivalents (METs)/hour/week). Carotid ultrasound was used to measure carotid intima media thickness (IMT). The SphygmoCor System was used to measure pulse wave velocity (PWV), and central and peripheral augmentation index (CAIx and PAIx). The B-pro device was used to measure ambulatory arterial stiffness index (AASI). Median counts/minute was 244.37 and mean METs/hour/week was 11.49. Physical activity showed an inverse correlation with PAIx (r = -0.179; p < 0.01) and vigorous activity day time with IMT (r = -0.174), CAIx (r = -0.217) and PAIx (r = -0.324) (p < 0.01, all). Sedentary activity day time was correlated positively with CAIx (r = 0.103; p < 0.05). In multiple regression analysis, after adjusting for confounding factors, the inverse association of CAIx with counts/minute and the time spent in moderate and vigorous activity were maintained as well as the positive association with sedentary activity day time (p < 0.05). Physical activity, assessed by counts/minute, and the amount of time spent in moderate, vigorous/very vigorous physical activity, showed an inverse association with CAIx. Likewise, the time spent in sedentary activity was positively associated with the CAIx. Clinical Trials.gov Identifier: NCT01083082. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Directed and persistent movement arises from mechanochemistry of the ParA/ParB system.

PubMed

Hu, Longhua; Vecchiarelli, Anthony G; Mizuuchi, Kiyoshi; Neuman, Keir C; Liu, Jian

2015-12-22

The segregation of DNA before cell division is essential for faithful genetic inheritance. In many bacteria, segregation of low-copy number plasmids involves an active partition system composed of a nonspecific DNA-binding ATPase, ParA, and its stimulator protein ParB. The ParA/ParB system drives directed and persistent movement of DNA cargo both in vivo and in vitro. Filament-based models akin to actin/microtubule-driven motility were proposed for plasmid segregation mediated by ParA. Recent experiments challenge this view and suggest that ParA/ParB system motility is driven by a diffusion ratchet mechanism in which ParB-coated plasmid both creates and follows a ParA gradient on the nucleoid surface. However, the detailed mechanism of ParA/ParB-mediated directed and persistent movement remains unknown. Here, we develop a theoretical model describing ParA/ParB-mediated motility. We show that the ParA/ParB system can work as a Brownian ratchet, which effectively couples the ATPase-dependent cycling of ParA-nucleoid affinity to the motion of the ParB-bound cargo. Paradoxically, this resulting processive motion relies on quenching diffusive plasmid motion through a large number of transient ParA/ParB-mediated tethers to the nucleoid surface. Our work thus sheds light on an emergent phenomenon in which nonmotor proteins work collectively via mechanochemical coupling to propel cargos-an ingenious solution shaped by evolution to cope with the lack of processive motor proteins in bacteria.

ParABS Systems of the Four Replicons of Burkholderia cenocepacia: New Chromosome Centromeres Confer Partition Specificity†

PubMed Central

Dubarry, Nelly; Pasta, Franck; Lane, David

2006-01-01

Most bacterial chromosomes carry an analogue of the parABS systems that govern plasmid partition, but their role in chromosome partition is ambiguous. parABS systems might be particularly important for orderly segregation of multipartite genomes, where their role may thus be easier to evaluate. We have characterized parABS systems in Burkholderia cenocepacia, whose genome comprises three chromosomes and one low-copy-number plasmid. A single parAB locus and a set of ParB-binding (parS) centromere sites are located near the origin of each replicon. ParA and ParB of the longest chromosome are phylogenetically similar to analogues in other multichromosome and monochromosome bacteria but are distinct from those of smaller chromosomes. The latter form subgroups that correspond to the taxa of their hosts, indicating evolution from plasmids. The parS sites on the smaller chromosomes and the plasmid are similar to the “universal” parS of the main chromosome but with a sequence specific to their replicon. In an Escherichia coli plasmid stabilization test, each parAB exhibits partition activity only with the parS of its own replicon. Hence, parABS function is based on the independent partition of individual chromosomes rather than on a single communal system or network of interacting systems. Stabilization by the smaller chromosome and plasmid systems was enhanced by mutation of parS sites and a promoter internal to their parAB operons, suggesting autoregulatory mechanisms. The small chromosome ParBs were found to silence transcription, a property relevant to autoregulation. PMID:16452432

Protease-activated receptor 1 and 2 contribute to angiotensin II-induced activation of adventitial fibroblasts from rat aorta

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

He, Rui-Qing; Tang, Xiao-Feng; Zhang, Bao-Li

Adventitial fibroblasts (AFs) can be activated by angiotensin II (Ang II) and exert pro-fibrotic and pro-inflammatory effects in vascular remodeling. Protease-activated receptor (PAR) 1 and 2 play a significant role in fibrogenic and inflammatory diseases. The present study hypothesized that PAR1 and PAR2 are involved in Ang II-induced AF activation and contribute to adventitial remodeling. We found that direct activation of PAR1 and PAR2 with PAR1-AP and PAR2-AP led to AF activation, including proliferation and differentiation of AFs, extracellular matrix synthesis, as well as production of pro-fibrotic cytokine TGF-β and pro-inflammatory cytokines IL-6 and MCP-1. Furthermore, PAR1 and PAR2 mediatedmore » Ang II-induced AF activation, since both PAR1 and PAR2 antagonists inhibited Ang II-induced proliferation, migration, differentiation, extracellular matrix synthesis and production of pro-fibrotic and pro-inflammatory cytokines in AFs. Finally, mechanistic study showed that Ang II, via Ang II type I receptor (AT1R), upregulated both PAR1 and PAR2 expression, and transactivated PAR1 and PAR2, as denoted by internalization of both proteins. In conclusion, our results suggest that PAR1 and PAR2 play a critical role in Ang II-induced AF activation, and this may contribute to adventitia-related pathological changes. - Highlights: • Direct activation of PAR1 and PAR2 led to adventitial fibroblast (AF) activation. • PAR1 and PAR2 antagonists attenuated Ang II-induced AF activation. • Ang II induced the upregulation and transactivation of PAR1/PAR2 in AFs.« less

Ultrasound-Guided Pulsed Radiofrequency Stimulation of Posterior Tibial Nerve: A Potential Novel Intervention for Recalcitrant Plantar Fasciitis.

PubMed

Wu, Yung-Tsan; Chang, Chih-Ya; Chou, Yu-Ching; Yeh, Chun-Chang; Li, Tsung-Ying; Chu, Heng-Yi; Chen, Liang-Cheng

2017-05-01

To evaluate the therapeutic benefit of ultrasound-guided pulsed radiofrequency (PRF) stimulation at the posterior tibial nerve (PTN) in patients with recalcitrant plantar fasciitis (PF). A prospective, randomized, double-blinded, placebo-controlled trial (12-wk follow-up). Outpatient local medical center settings. Patients (N=36) with recalcitrant PF underwent randomization, and all were included in the final data analysis. Patients in the PRF group were treated with 1 dose of ultrasound-guided PRF stimulation at the PTN, and those in the control group received 1 dose of 2% lidocaine, 0.5mL, injected at the PTN under ultrasound guidance. The visual analog scale (first-step and overall pain), American Orthopedic Foot-Ankle Society (AOFAS) ankle-hindfoot scale, and ultrasonographic thickness of the plantar fascia were evaluated at 1, 4, 8, and 12 weeks after treatment. Thirty-six patients (20 feet per group) completed the study. The PRF group had a significantly larger improvement in first-step pain, overall pain, and AOFAS score (all P<.001), as well as plantar fascia thickness (P<.05), compared with those of the control group at all observed time points. This study shows that ultrasound-guided PRF stimulation at the PTN is effective for treating recalcitrant PF. This simple, reproducible method could be a novel strategy for managing recalcitrant PF. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Guided Z mode propagation observed in the OEDIPUS A tethered rocket experiment

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

James, H.G.

1991-10-01

The tethered sounding rocket payload OEDIPUS A conducted bistatic propagation experiments on plasma waves in the auroral ionosphere. Synchronized sweeps of the frequency range 0-5 MHz by the 2-W transmitter high-frequency exciter (HEX) on the upper end of the tether and its associated receiver for exciter (REX) on the lower end have produced signatures of quasi-electrostatic waves guided along field-aligned depletions of ambient density. The propagation is in the slow Z mode, between the plasma frequency f{sub p} and the upper hybrid resonance frequency f{sub uhr} when f{sub p} is greater than the cyclotron frequency. The mode identification is basedmore » on payload measurements of f{sub p}. These waves have signal delays of about 1 ms. The delays are much greater than expected for free-space propagation over the transmitter-receiver separation distance which varies up to 960 m during the flight. The transmitted pulses typically appear inside a frequency bandwidth of about 100 kHz just above the plasma frequency, but occasionally occupy most of the available bandwidth, {approx equal}300 kHz, between f{sub p} and f{sub uhr}. The observed delays and the stretching by a factor of 3 of the transmitted 300-{mu}s pulses are accounted for with two-dimensional ray tracing using a complete electromagnetic solution of the hot plasma dispersion relation. Delayed Z mode pulses appear in about 20% of the ionograms. Given the weakness of the HEX transmitter and the abundance of examples obtained during the flight, guiding of natural Z mode emissions in the auroral ionosphere may be efficient and widespread.« less

Thrombin Receptors and Protease-Activated Receptor-2 in Human Placentation

PubMed Central

O’Brien, Peter J.; Koi, Hideki; Parry, Samuel; Brass, Lawrence F.; Strauss, Jerome F.; Wang, Li-Peng; Tomaszewski, John E.; Christenson, Lane K.

2003-01-01

Proteolysis of the thrombin receptor, protease activated receptor-1 (PAR1), may enhance normal and pathological cellular invasion, and indirect evidence suggests that activation of PAR1 expressed by invasive extravillous trophoblasts (EVTs) influences human placentation. Here we describe PAR1, PAR2, and PAR3 protein distribution in the developing human placenta and implicate PAR1 and PAR2 activation in functions central to EVT invasion. PAR1, PAR2, and PAR3 are expressed in cultured 8- to 13-week-old EVTs, and in situ in 18- to 20-week-old placental syncytiotrophoblasts and invasive trophoblasts. Thrombin, but not the PAR2 agonist peptide SLIGKV, inhibited proliferation in cultured EVTs, although both agonists stimulated phosphoinositide hydrolysis and EVT invasion through Matrigel barriers. Thrombin-induced phosphoinositide hydrolysis was completely inhibited and the thrombin effect on proliferation was prevented when PAR1 cleavage was first blocked with specific monoclonal antibodies, indicating that PAR1 is the predominant thrombin receptor on EVTs. Together these results support a role for PAR1, and potentially PAR2 and PAR3 in the invasive phase of human placentation. PMID:14507634

175 fs-long pulses from a high-power single-mode Er-doped fiber laser at 1550 nm

NASA Astrophysics Data System (ADS)

Elahi, Parviz; Kalaycıoğlu, Hamit; Li, Huihui; Akçaalan, Önder; Ilday, F. Ömer

2017-11-01

Development of Er-doped ultrafast lasers have lagged behind the corresponding developments in Yb- and Tm-doped lasers, in particular, fiber lasers. Various applications benefit from operation at a central wavelength of 1.5 μm and its second harmonic, including emerging applications such as 3D processing of silicon and 3D printing based on two-photon polymerization. We report a simple, robust fiber master oscillator power amplifier operating at 1.55 μm, implementing chirp pulse amplification using single-mode fibers for diffraction-limited beam quality. The laser generates 80 nJ pulses at a repetition rate of 43 MHz, corresponding to an average power of 3.5 W, which can be compressed down to 175 fs. The generation of short pulses was achieved using a design which is guided by numerical simulations of pulse propagation and amplification and manages to overturn gain narrowing with self-phase modulation, without invoking excessive Raman scattering processes. The seed source for the two-stage amplifier is a dispersion-managed passively mode-locked oscillator, which generates a ∼40 nm-wide spectrum and 1.7-ps linearly chirped pulses.

The signaling adapter Gab1 regulates cell polarity by acting as a PAR protein scaffold

PubMed Central

Yang, Ziqiang; Xue, Bin; Umitsu, Masataka; Ikura, Mitsuhiko; Muthuswamy, Senthil K.; Neel, Benjamin G.

2012-01-01

Summary Cell polarity plays a key role in development and is disrupted in tumors, yet the molecules and mechanisms that regulate polarity remain poorly defined. We found that the scaffolding adaptor GAB1 interacts with two polarity proteins, PAR1 and PAR3. GAB1 binds PAR1 and enhances its kinase activity. GAB1 brings PAR1 and PAR3 into a transient complex, stimulating PAR3 phosphorylation by PAR1. GAB1 and PAR6 bind the PAR3 PDZ1 domain and thereby compete for PAR3 binding. Consequently, GAB1 depletion causes PAR3 hypo-phosphorylation and increases PAR3/PAR6 complex formation, resulting in accelerated and enhanced tight junction formation, increased trans-epithelial resistance and lateral domain shortening. Conversely, GAB1 over-expression, in a PAR1/PAR3-dependent manner, disrupts epithelial apical-basal polarity, promotes multi-lumen cyst formation, and enhances growth factor-induced epithelial cell scattering. Our results identify GAB1 as a novel negative regulator of epithelial cell polarity that functions as a scaffold for modulating PAR protein complexes on the lateral membrane. PMID:22883624

Directed and persistent movement arises from mechanochemistry of the ParA/ParB system

NASA Astrophysics Data System (ADS)

Hu, Longhua; Vecchiarelli, Anthony G.; Mizuuchi, Kiyoshi; Neuman, Keir C.; Liu, Jian

The segregation of DNA prior to cell division is essential for faithful genetic inheritance. In many bacteria, segregation of the low-copy-number plasmids involves an active partition system composed of ParA ATPase and its stimulator protein ParB. Recent experiments suggest that ParA/ParB system motility is driven by a diffusion-ratchet mechanism in which ParB-coated plasmid both creates and follows a ParA gradient on the nucleoid surface. However, the detailed mechanism of ParA/ParB-mediated directed and persistent movement remains unknown. We develop a theoretical model describing ParA/ParB-mediated motility. We show that the ParA/ParB system can work as a Brownian ratchet, which effectively couples the ATPase-dependent cycling of ParA-nucleoid affinity to the motion of the ParB bound cargo. Paradoxically, the resulting processive motion relies on quenching diffusive plasmid motion through a large number of transient ParA/ParB-mediated tethers to the nucleoid surface. Our work sheds light on a new emergent phenomenon in which non-motor proteins work collectively via mechanochemical coupling to propel cargos -- an ingenious solution shaped by evolution to cope with the lack of processive motor proteins in bacteria.

Compensated second-order recoupling: application to third spin assisted recoupling†

PubMed Central

Giffard, Mathilde; Hediger, Sabine; Lewandowski, Józef R.; Bardet, Michel; Simorre, Jean-Pierre; Griffin, Robert G.; De Paëpe, Gaël

2015-01-01

We consider the effect of phase shifts in the context of second-order recoupling techniques in solid-state NMR. Notably we highlight conditions leading to significant improvements for the Third Spin Assisted Recoupling (TSAR) mechanism and demonstrate the benefits of resulting techniques for detecting long-distance transfer in biomolecular systems. The modified pulse sequences of PAR and PAIN-CP, Phase-Shifted Proton Assisted Recoupling (AH-PS-PAR) and Phase-Shifted Proton-Assisted Insensitive Nuclei Cross Polarization (ABH-PS-PAIN-CP), still rely on cross terms between heteronuclear dipolar couplings involving assisting protons that mediate zero-quantum polarization transfer between low-γ nuclei (13C–13C, 15N–15N, 15N–13C polarization transfer). Using Average Hamiltonian Theory we show that phase inversion compensates off-resonance contributions and yields improved polarization transfer as well as substantial broadening of the matching conditions. PS-TSAR greatly improves on the standard TSAR based methods because it alleviates their sensitivity to precise RF settings which significantly enhances robustness of the experiments. We demonstrate these new methods on a 19.6 kDa protein (U–[15N, 13C]-YajG) at high magnetic fields (up to 900 MHz 1H frequency) and fast sample spinning (up to 65 kHz MAS frequency). PMID:22513727

Directed and persistent movement arises from mechanochemistry of the ParA/ParB system

PubMed Central

Hu, Longhua; Vecchiarelli, Anthony G.; Mizuuchi, Kiyoshi; Neuman, Keir C.; Liu, Jian

2015-01-01

The segregation of DNA before cell division is essential for faithful genetic inheritance. In many bacteria, segregation of low-copy number plasmids involves an active partition system composed of a nonspecific DNA-binding ATPase, ParA, and its stimulator protein ParB. The ParA/ParB system drives directed and persistent movement of DNA cargo both in vivo and in vitro. Filament-based models akin to actin/microtubule-driven motility were proposed for plasmid segregation mediated by ParA. Recent experiments challenge this view and suggest that ParA/ParB system motility is driven by a diffusion ratchet mechanism in which ParB-coated plasmid both creates and follows a ParA gradient on the nucleoid surface. However, the detailed mechanism of ParA/ParB-mediated directed and persistent movement remains unknown. Here, we develop a theoretical model describing ParA/ParB-mediated motility. We show that the ParA/ParB system can work as a Brownian ratchet, which effectively couples the ATPase-dependent cycling of ParA–nucleoid affinity to the motion of the ParB-bound cargo. Paradoxically, this resulting processive motion relies on quenching diffusive plasmid motion through a large number of transient ParA/ParB-mediated tethers to the nucleoid surface. Our work thus sheds light on an emergent phenomenon in which nonmotor proteins work collectively via mechanochemical coupling to propel cargos—an ingenious solution shaped by evolution to cope with the lack of processive motor proteins in bacteria. PMID:26647183

A Fiber Bragg Grating Sensor for Radial Artery Pulse Waveform Measurement.

PubMed

Jia, Dagong; Chao, Jing; Li, Shuai; Zhang, Hongxia; Yan, Yingzhan; Liu, Tiegen; Sun, Ye

2018-04-01

In this paper, we report the design and experimental validation of a novel optical sensor for radial artery pulse measurement based on fiber Bragg grating (FBG) and lever amplification mechanism. Pulse waveform analysis is a diagnostic tool for clinical examination and disease diagnosis. High fidelity radial artery pulse waveform has been investigated in clinical studies for estimating central aortic pressure, which is proved to be predictors of cardiovascular diseases. As a three-dimensional cylinder, the radial artery needs to be examined from different locations to achieve optimal pulse waveform for estimation and diagnosis. The proposed optical sensing system is featured as high sensitivity and immunity to electromagnetic interference for multilocation radial artery pulse waveform measurement. The FBG sensor can achieve the sensitivity of 8.236 nm/N, which is comparable to a commonly used electrical sensor. This FBG-based system can provide high accurate measurement, and the key characteristic parameters can be then extracted from the raw signals for clinical applications. The detecting performance is validated through experiments guided by physicians. In the experimental validation, we applied this sensor to measure the pulse waveforms at various positions and depths of the radial artery in the wrist according to the diagnostic requirements. The results demonstrate the high feasibility of using optical systems for physiological measurement and using this FBG sensor for radial artery pulse waveform in clinical applications.

Development of variable-rate sprayer for nursery liner applications

USDA-ARS?s Scientific Manuscript database

Sensor-guided application technologies are needed to achieve constant spray deposition for the rapid growth of nursery liner trees during a growing season. An experimental real-time variable-rate sprayer that implemented 20 Hz ultrasonic sensors and pulse width modulation (PWM) solenoid valve-contro...

Intraoperative diagnostics and elimination of residual microtumours with plasmonic nanobubbles

NASA Astrophysics Data System (ADS)

Lukianova-Hleb, Ekaterina Y.; Kim, Yoo-Shin; Belatsarkouski, Ihor; Gillenwater, Ann M.; O'Neill, Brian E.; Lapotko, Dmitri O.

2016-06-01

Failure of cancer surgery to intraoperatively detect and eliminate microscopic residual disease (MRD) causes lethal recurrence and metastases, and the removal of important normal tissues causes excessive morbidity. Here, we show that a plasmonic nanobubble (PNB), a non-stationary laser pulse-activated nanoevent, intraoperatively detects and eliminates MRD in the surgical bed. PNBs were generated in vivo in head and neck cancer cells by systemically targeting tumours with gold colloids and locally applying near-infrared, low-energy short laser pulses, and were simultaneously detected with an acoustic probe. In mouse models, between 3 and 30 residual cancer cells and MRD (undetectable with current methods) were non-invasively detected up to 4 mm deep in the surgical bed within 1 ms. In resectable MRD, PNB-guided surgery prevented local recurrence and delivered 100% tumour-free survival. In unresectable MRD, PNB nanosurgery improved survival twofold compared with standard surgery. Our results show that PNB-guided surgery and nanosurgery can rapidly and precisely detect and remove MRD in simple intraoperative procedures.

A pulse coding and decoding strategy to perform Lamb wave inspections using simultaneously multiple actuators

NASA Astrophysics Data System (ADS)

De Marchi, Luca; Marzani, Alessandro; Moll, Jochen; Kudela, Paweł; Radzieński, Maciej; Ostachowicz, Wiesław

2017-07-01

The performance of Lamb wave based monitoring systems, both in terms of diagnosis time and data complexity, can be enhanced by increasing the number of transducers used to actuate simultaneously the guided waves in the inspected medium. However, in case of multiple simultaneously-operated actuators the interference among the excited wave modes within the acquired signals has to be considered for the further processing. To this aim, in this work a code division strategy based on the Warped Frequency Transform is presented. At first, the proposed procedure encodes actuation pulses using Gold sequences. Next, for each considered actuator the acquired signals are compensated from dispersion by cross correlating the warped version of the actuated and received signals. Compensated signals form the base for a final wavenumber imaging meant at emphasizing defects and or anomalies by removing incident wavefield and edge reflections. The proposed strategy is tested numerically, and validated through an experiment in which guided waves are actuated in a plate by four piezoelectric transducers operating simultaneously.

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

Barnard, John J.; Schenkel, Thomas

Intense, pulsed ion beams locally heat materials and deliver dense electronic excitations that can induce material modifications and phase transitions. Material properties can potentially be stabilized by rapid quenching. Pulsed ion beams with pulse lengths of order ns have recently become available for materials processing. Here, we optimize mask geometries for local modification of materials by intense ion pulses. The goal is to rapidly excite targets volumetrically to the point where a phase transition or local lattice reconstruction is induced followed by rapid cooling that stabilizes desired material's properties fast enough before the target is altered or damaged by, e.g.,more » hydrodynamic expansion. By using a mask, the longitudinal dimension can be large compared to the transverse dimension, allowing the possibility of rapid transverse cooling. We performed HYDRA simulations that calculate peak temperatures for a series of excitation conditions and cooling rates of silicon targets with micro-structured masks and compare these to a simple analytical model. In conclusion, the model gives scaling laws that can guide the design of targets over a wide range of pulsed ion beam parameters.« less

Optimization of ultrasound parameters of myocardial cavitation microlesions for therapeutic application.

PubMed

Miller, Douglas L; Dou, Chunyan; Owens, Gabe E; Kripfgans, Oliver D

2014-06-01

Intermittent high intensity ultrasound scanning with contrast microbubbles can induce scattered cavitation microlesions in the myocardium, which may be of value for tissue reduction therapy. Anesthetized rats were treated in a heated water bath with 1.5 MHz focused ultrasound pulses, guided by an 8 MHz imaging transducer. The relative efficacy with 2 or 4 MPa pulses, 1:4 or 1:8 trigger intervals and 5 or 10 cycle pulses was explored in six groups. Electrocardiogram premature complexes (PCs) induced by the triggered pulse bursts were counted, and Evans blue stained cardiomyocyte scores (SCSs) were obtained. The increase from 2 to 4 MPa produced significant increases in PCs and SCSs and eliminated an anticipated decline in the rate of PC induction with time, which might hinder therapeutic efficacy. Increased intervals and pulse durations did not yield significant increases in the effects. The results suggest that cavitation microlesion production can be refined and potentially lead to a clinically robust therapeutic method. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Selective Removal of Demineralization Using Near Infrared Cross Polarization Reflectance and a Carbon Dioxide Laser.

PubMed

Chan, Kenneth H; Fried, Daniel

2012-02-09

Lasers can ablate/remove tissue in a non-contact mode of operation and a pulsed laser beam does not interfere with the ability to image the tooth surface, therefore lasers are ideally suited for integration with imaging devices for image-guided ablation. Laser energy can be rapidly and efficiently delivered to tooth surfaces using a digitally controlled laser beam scanning system for precise and selective laser ablation with minimal loss of healthy tissues. Under the appropriate irradiation conditions such laser energy can induce beneficial chemical and morphological changes in the walls of the drilled cavity that can increase resistance to further dental decay and produce surfaces with enhanced adhesive properties to restorative materials. Previous studies have shown that images acquired using near-IR transillumination, optical coherence tomography and fluorescence can be used to guide the laser for selective removal of demineralized enamel. Recent studies have shown that NIR reflectance measurements at 1470-nm can be used to obtain images of enamel demineralization with very high contrast. The purpose of this study was to demonstrate that image guided ablation of occlusal lesions can be successfully carried out using a NIR reflectance imaging system coupled with a carbon dioxide laser operating at 9.3-μm with high pulse repetition rates.

The tail of the ParG DNA segregation protein remodels ParF polymers and enhances ATP hydrolysis via an arginine finger-like motif

PubMed Central

Barillà, Daniela; Carmelo, Emma; Hayes, Finbarr

2007-01-01

The ParF protein of plasmid TP228 belongs to the ubiquitous superfamily of ParA ATPases that drive DNA segregation in bacteria. ATP-bound ParF polymerizes into multistranded filaments. The partner protein ParG is dimeric, consisting of C-termini that interweave into a ribbon–helix–helix domain contacting the centromeric DNA and unstructured N-termini. ParG stimulates ATP hydrolysis by ParF ≈30-fold. Here, we establish that the mobile tails of ParG are crucial for this enhancement and that arginine R19 within the tail is absolutely required for activation of ParF nucleotide hydrolysis. R19 is part of an arginine finger-like loop in ParG that is predicted to intercalate into the ParF nucleotide-binding pocket thereby promoting ATP hydrolysis. Significantly, mutations of R19 abrogated DNA segregation in vivo, proving that intracellular stimulation of ATP hydrolysis by ParG is a key regulatory process for partitioning. Furthermore, ParG bundles ParF-ATP filaments as well as promoting nucleotide-independent polymerization. The N-terminal flexible tail is required for both activities, because N-terminal ΔParG polypeptides are defective in both functions. Strikingly, the critical arginine finger-like residue R19 is dispensable for ParG-mediated remodeling of ParF polymers, revealing that the ParG N-terminal tail possesses two separable activities in the interplay with ParF: a catalytic function during ATP hydrolysis and a mechanical role in modulation of polymerization. We speculate that activation of nucleotide hydrolysis via an arginine finger loop may be a conserved, regulatory mechanism of ParA family members and their partner proteins, including ParA-ParB and Soj-Spo0J that mediate DNA segregation and MinD-MinE that determine septum localization. PMID:17261809

The tail of the ParG DNA segregation protein remodels ParF polymers and enhances ATP hydrolysis via an arginine finger-like motif.

PubMed

Barillà, Daniela; Carmelo, Emma; Hayes, Finbarr

2007-02-06

The ParF protein of plasmid TP228 belongs to the ubiquitous superfamily of ParA ATPases that drive DNA segregation in bacteria. ATP-bound ParF polymerizes into multistranded filaments. The partner protein ParG is dimeric, consisting of C-termini that interweave into a ribbon-helix-helix domain contacting the centromeric DNA and unstructured N-termini. ParG stimulates ATP hydrolysis by ParF approximately 30-fold. Here, we establish that the mobile tails of ParG are crucial for this enhancement and that arginine R19 within the tail is absolutely required for activation of ParF nucleotide hydrolysis. R19 is part of an arginine finger-like loop in ParG that is predicted to intercalate into the ParF nucleotide-binding pocket thereby promoting ATP hydrolysis. Significantly, mutations of R19 abrogated DNA segregation in vivo, proving that intracellular stimulation of ATP hydrolysis by ParG is a key regulatory process for partitioning. Furthermore, ParG bundles ParF-ATP filaments as well as promoting nucleotide-independent polymerization. The N-terminal flexible tail is required for both activities, because N-terminal DeltaParG polypeptides are defective in both functions. Strikingly, the critical arginine finger-like residue R19 is dispensable for ParG-mediated remodeling of ParF polymers, revealing that the ParG N-terminal tail possesses two separable activities in the interplay with ParF: a catalytic function during ATP hydrolysis and a mechanical role in modulation of polymerization. We speculate that activation of nucleotide hydrolysis via an arginine finger loop may be a conserved, regulatory mechanism of ParA family members and their partner proteins, including ParA-ParB and Soj-Spo0J that mediate DNA segregation and MinD-MinE that determine septum localization.

Novel role for proteinase-activated receptor 2 (PAR2) in membrane trafficking of proteinase-activated receptor 4 (PAR4).

PubMed

Cunningham, Margaret R; McIntosh, Kathryn A; Pediani, John D; Robben, Joris; Cooke, Alexandra E; Nilsson, Mary; Gould, Gwyn W; Mundell, Stuart; Milligan, Graeme; Plevin, Robin

2012-05-11

Proteinase-activated receptors 4 (PAR(4)) is a class A G protein-coupled receptor (GPCR) recognized through the ability of serine proteases such as thrombin and trypsin to mediate receptor activation. Due to the irreversible nature of activation, a fresh supply of receptor is required to be mobilized to the cell surface for responsiveness to agonist to be sustained. Unlike other PAR subtypes, the mechanisms regulating receptor trafficking of PAR(4) remain unknown. Here, we report novel features of the intracellular trafficking of PAR(4) to the plasma membrane. PAR(4) was poorly expressed at the plasma membrane and largely retained in the endoplasmic reticulum (ER) in a complex with the COPI protein subunit β-COP1. Analysis of the PAR(4) protein sequence identified an arginine-based (RXR) ER retention sequence located within intracellular loop-2 (R(183)AR → A(183)AA), mutation of which allowed efficient membrane delivery of PAR(4). Interestingly, co-expression with PAR(2) facilitated plasma membrane delivery of PAR(4), an effect produced through disruption of β-COP1 binding and facilitation of interaction with the chaperone protein 14-3-3ζ. Intermolecular FRET studies confirmed heterodimerization between PAR(2) and PAR(4). PAR(2) also enhanced glycosylation of PAR(4) and activation of PAR(4) signaling. Our results identify a novel regulatory role for PAR(2) in the anterograde traffic of PAR(4). PAR(2) was shown to both facilitate and abrogate protein interactions with PAR(4), impacting upon receptor localization and cell signal transduction. This work is likely to impact markedly upon the understanding of the receptor pharmacology of PAR(4) in normal physiology and disease.

PAR proteins regulate maintenance-phase myosin dynamics during Caenorhabditis elegans zygote polarization

PubMed Central

Small, Lawrence E.; Dawes, Adriana T.

2017-01-01

Establishment of anterior–posterior polarity in the Caenorhabditis elegans zygote requires two different processes: mechanical activity of the actin–myosin cortex and biochemical activity of partitioning-defective (PAR) proteins. Here we analyze how PARs regulate the behavior of the cortical motor protein nonmuscle myosin (NMY-2) to complement recent efforts that investigate how PARs regulate the Rho GTPase CDC-42, which in turn regulates the actin-myosin cortex. We find that PAR-3 and PAR-6 concentrate CDC-42–dependent NMY-2 in the anterior cortex, whereas PAR-2 inhibits CDC-42–dependent NMY-2 in the posterior domain by inhibiting PAR-3 and PAR-6. In addition, we find that PAR-1 and PAR-3 are necessary for inhibiting movement of NMY-2 across the cortex. PAR-1 protects NMY-2 from being moved across the cortex by forces likely originating in the cytoplasm. Meanwhile, PAR-3 stabilizes NMY-2 against PAR-2 and PAR-6 dynamics on the cortex. We find that PAR signaling fulfills two roles: localizing NMY-2 to the anterior cortex and preventing displacement of the polarized cortical actin–myosin network. PMID:28615321

Lignes directrices sur la prise en charge en soins primaires des céphalées chez l’adulte

PubMed Central

Becker, Werner J.; Findlay, Ted; Moga, Carmen; Scott, N. Ann; Harstall, Christa; Taenzer, Paul

2015-01-01

Résumé Objectif Accroître l’utilisation d’approches éclairées par des données probantes pour diagnostiquer, investiguer et traiter en soins primaires les céphalées des patients. Qualité des données Une recherche documentaire exhaustive a été effectuée pour trouver des lignes directrices et des révisions systématiques publiées entre janvier 2000 et mai 2011. La grille d’évaluation de la qualité des recommandations pour la pratique clinique AGREE a servi à l’analyse critique des lignes directrices. Les 6 guides de pratique clinique de la plus grande qualité ont servi de base dans le processus d’adaptation. Message principal Un groupe d’élaboration multidisciplinaire de professionnels des soins primaires ont formulé 91 recommandations précises à l’aide d’un processus consensuel. Les recommandations portent sur le diagnostic, l’investigation et la prise en charge de la migraine, de la céphalée de tension, de la céphalée due à une surmédication et de la céphalée vasculaire de Horton. Conclusion Un guide de pratique clinique adapté au contexte des soins de santé au Canada a été produit en suivant un processus d’adaptation de lignes directrices dans le but d’aider les professionnels de toutes les disciplines des soins primaires à dispenser des soins éclairés par des données probantes aux patients souffrant de céphalées.

Pulsed cavitational ultrasound for non-invasive chordal cutting guided by real-time 3D echocardiography.

PubMed

Villemain, Olivier; Kwiecinski, Wojciech; Bel, Alain; Robin, Justine; Bruneval, Patrick; Arnal, Bastien; Tanter, Mickael; Pernot, Mathieu; Messas, Emmanuel

2016-10-01

Basal chordae surgical section has been shown to be effective in reducing ischaemic mitral regurgitation (IMR). Achieving this section by non-invasive mean can considerably decrease the morbidity of this intervention on already infarcted myocardium. We investigated in vitro and in vivo the feasibility and safety of pulsed cavitational focused ultrasound (histotripsy) for non-invasive chordal cutting guided by real-time 3D echocardiography. Experiments were performed on 12 sheep hearts, 5 in vitro on explanted sheep hearts and 7 in vivo on beating sheep hearts. In vitro, the mitral valve (MV) apparatus including basal and marginal chordae was removed and fixed on a holder in a water tank. High-intensity ultrasound pulses were emitted from the therapeutic device (1-MHz focused transducer, pulses of 8 µs duration, peak negative pressure of 17 MPa, repetition frequency of 100 Hz), placed at a distance of 64 mm under 3D echocardiography guidance. In vivo, after sternotomy, the same therapeutic device was applied on the beating heart. We analysed MV coaptation and chordae by real-time 3D echocardiography before and after basal chordal cutting. After sacrifice, the MV apparatus were harvested for anatomical and histological post-mortem explorations to confirm the section of the chordae. In vitro, all chordae were completely cut after a mean procedure duration of 5.5 ± 2.5 min. The procedure duration was found to increase linearly with the chordae diameter. In vivo, the central basal chordae of the anterior leaflet were completely cut. The mean procedure duration was 20 ± 9 min (min = 14, max = 26). The sectioned chordae was visible on echocardiography, and MV coaptation remained normal with no significant mitral regurgitation. Anatomical and histological post-mortem explorations of the hearts confirmed the section of the chordae. Histotripsy guided by 3D echo achieved successfully to cut MV chordae in vitro and in vivo in beating heart. We hope that this technique will open the door in the near future to the non-invasive treatment of functional IMR. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Analysis of ParB-centromere interactions by multiplex SPR imaging reveals specific patterns for binding ParB in six centromeres of Burkholderiales chromosomes and plasmids

PubMed Central

Pillet, Flavien; Passot, Fanny Marie

2017-01-01

Bacterial centromeres–also called parS, are cis-acting DNA sequences which, together with the proteins ParA and ParB, are involved in the segregation of chromosomes and plasmids. The specific binding of ParB to parS nucleates the assembly of a large ParB/DNA complex from which ParA—the motor protein, segregates the sister replicons. Closely related families of partition systems, called Bsr, were identified on the chromosomes and large plasmids of the multi-chromosomal bacterium Burkholderia cenocepacia and other species from the order Burkholeriales. The centromeres of the Bsr partition families are 16 bp palindromes, displaying similar base compositions, notably a central CG dinucleotide. Despite centromeres bind the cognate ParB with a narrow specificity, weak ParB-parS non cognate interactions were nevertheless detected between few Bsr partition systems of replicons not belonging to the same genome. These observations suggested that Bsr partition systems could have a common ancestry but that evolution mostly erased the possibilities of cross-reactions between them, in particular to prevent replicon incompatibility. To detect novel similarities between Bsr partition systems, we have analyzed the binding of six Bsr parS sequences and a wide collection of modified derivatives, to their cognate ParB. The study was carried out by Surface Plasmon Resonance imaging (SPRi) mulitplex analysis enabling a systematic survey of each nucleotide position within the centromere. We found that in each parS some positions could be changed while maintaining binding to ParB. Each centromere displays its own pattern of changes, but some positions are shared more or less widely. In addition from these changes we could speculate evolutionary links between these centromeres. PMID:28562673

Analysis of ParB-centromere interactions by multiplex SPR imaging reveals specific patterns for binding ParB in six centromeres of Burkholderiales chromosomes and plasmids.

PubMed

Pillet, Flavien; Passot, Fanny Marie; Pasta, Franck; Anton Leberre, Véronique; Bouet, Jean-Yves

2017-01-01

Bacterial centromeres-also called parS, are cis-acting DNA sequences which, together with the proteins ParA and ParB, are involved in the segregation of chromosomes and plasmids. The specific binding of ParB to parS nucleates the assembly of a large ParB/DNA complex from which ParA-the motor protein, segregates the sister replicons. Closely related families of partition systems, called Bsr, were identified on the chromosomes and large plasmids of the multi-chromosomal bacterium Burkholderia cenocepacia and other species from the order Burkholeriales. The centromeres of the Bsr partition families are 16 bp palindromes, displaying similar base compositions, notably a central CG dinucleotide. Despite centromeres bind the cognate ParB with a narrow specificity, weak ParB-parS non cognate interactions were nevertheless detected between few Bsr partition systems of replicons not belonging to the same genome. These observations suggested that Bsr partition systems could have a common ancestry but that evolution mostly erased the possibilities of cross-reactions between them, in particular to prevent replicon incompatibility. To detect novel similarities between Bsr partition systems, we have analyzed the binding of six Bsr parS sequences and a wide collection of modified derivatives, to their cognate ParB. The study was carried out by Surface Plasmon Resonance imaging (SPRi) mulitplex analysis enabling a systematic survey of each nucleotide position within the centromere. We found that in each parS some positions could be changed while maintaining binding to ParB. Each centromere displays its own pattern of changes, but some positions are shared more or less widely. In addition from these changes we could speculate evolutionary links between these centromeres.

ParA and ParB coordinate chromosome segregation with cell elongation and division during Streptomyces sporulation

PubMed Central

Donczew, Magdalena; Mackiewicz, Paweł; Wróbel, Agnieszka; Flärdh, Klas; Zakrzewska-Czerwińska, Jolanta

2016-01-01

In unicellular bacteria, the ParA and ParB proteins segregate chromosomes and coordinate this process with cell division and chromosome replication. During sporulation of mycelial Streptomyces, ParA and ParB uniformly distribute multiple chromosomes along the filamentous sporogenic hyphal compartment, which then differentiates into a chain of unigenomic spores. However, chromosome segregation must be coordinated with cell elongation and multiple divisions. Here, we addressed the question of whether ParA and ParB are involved in the synchronization of cell-cycle processes during sporulation in Streptomyces. To answer this question, we used time-lapse microscopy, which allows the monitoring of growth and division of single sporogenic hyphae. We showed that sporogenic hyphae stop extending at the time of ParA accumulation and Z-ring formation. We demonstrated that both ParA and ParB affect the rate of hyphal extension. Additionally, we showed that ParA promotes the formation of massive nucleoprotein complexes by ParB. We also showed that FtsZ ring assembly is affected by the ParB protein and/or unsegregated DNA. Our results indicate the existence of a checkpoint between the extension and septation of sporogenic hyphae that involves the ParA and ParB proteins. PMID:27248800

High-speed optical phase-shifting apparatus

DOEpatents

Zortman, William A.

2016-11-08

An optical phase shifter includes an optical waveguide, a plurality of partial phase shifting elements arranged sequentially, and control circuitry electrically coupled to the partial phase shifting elements. The control circuitry is adapted to provide an activating signal to each of the N partial phase shifting elements such that the signal is delayed by a clock cycle between adjacent partial phase shifting elements in the sequence. The transit time for a guided optical pulse train between the input edges of consecutive partial phase shifting elements in the sequence is arranged to be equal to a clock cycle, thereby enabling pipelined processing of the optical pulses.

Microtubules induce self-organization of polarized PAR domains in C. elegans zygotes

PubMed Central

Motegi, Fumio; Zonies, Seth; Hao, Yingsong; Cuenca, Adrian A.; Griffin, Erik; Seydoux, Geraldine

2011-01-01

A hallmark of polarized cells is the segregation of the PAR polarity regulators into asymmetric domains at the cell cortex1, 2. Antagonistic interactions involving two conserved kinases, atypical protein kinase C (aPKC) and PAR-1, have been implicated in polarity maintenance1, 2, but the mechanisms that initiate the formation of asymmetric PAR domains are not understood. Here, we describe one pathway used by the sperm-donated centrosome to polarize the PAR proteins in Caenorhabditis elegans zygotes. Before polarization, cortical aPKC excludes PAR-1 kinase and its binding partner PAR-2 by phosphorylation. During symmetry breaking, microtubules nucleated by the centrosome locally protect PAR-2 from phosphorylation by aPKC, allowing PAR-2 and PAR-1 to access the cortex nearest the centrosome. Cortical PAR-1 phosphorylates PAR-3, causing the PAR-3/aPKC complex to leave the cortex. Our findings illustrate how microtubules, independent of actin dynamics, stimulate the self-organization of PAR proteins by providing local protection against a global barrier imposed by aPKC. PMID:21983565

PAR-1 and PAR-2 Expression Is Enhanced in Inflamed Odontoblast Cells.

PubMed

Alvarez, M M P; Moura, G E; Machado, M F M; Viana, G M; de Souza Costa, C A; Tjäderhane, L; Nader, H B; Tersariol, I L S; Nascimento, F D

2017-12-01

Protease-activated receptors (PARs) are G protein-coupled receptors, which are activated by proteolytical cleavage of the amino-terminus and act as sensors for extracellular proteases. We hypothesized that PAR-1 and PAR-2 can be modulated by inflammatory stimulus in human dental pulp cells. PAR-1 and PAR-2 gene expression in human pulp tissue and MDPC-23 cells were analyzed by quantitative polymerase chain reaction. Monoclonal PAR-1 and PAR-2 antibodies were used to investigate the cellular expression of these receptors using Western blot, flow cytometry, and confocal microscopy in MDPC-23 cells. Immunofluorescence assays of human intact and carious teeth were performed to assess the presence of PAR-1 and PAR-2 in the dentin-pulp complex. The results show for the first time that human odontoblasts and MDPC-23 cells constitutively express PAR-1 and PAR-2. PAR-2 activation increased significantly the messenger RNA expression of matrix metalloproteinase (MMP)-2, MMP-9, MMP-13, and MMP-14 in MDPC-23 cells ( P < 0.05), while the expression of these enzymes decreased significantly in the PAR-1 agonist group ( P < 0.05). The high-performance liquid chromatography and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry analysis showed the presence of MMP-13 activity cleaving PAR-1 at specific, noncanonical site TLDPRS 42 ↓F 43 LL in human dental pulp tissues. Also, we detected a presence of a trypsin-like activity cleaving PAR-2 at canonical site SKGR 20 ↓S 21 LIGRL in pulp tissues. Confocal microscopy analysis of human dentin-pulp complex showed intense positive staining of PAR-1 and PAR-2 in the odontoblast processes in dentinal tubules of carious teeth compared to intact ones. The present results support the hypothesis of activation of the upregulated PAR-1 and PAR-2 by endogenous proteases abundant during the inflammatory response in dentin-pulp complex.

Protease-activated receptor (PAR)2, but not PAR1, is involved in collateral formation and anti-inflammatory monocyte polarization in a mouse hind limb ischemia model.

PubMed

van den Hengel, Lisa G; Hellingman, Alwine A; Nossent, Anne Yael; van Oeveren-Rietdijk, Annemarie M; de Vries, Margreet R; Spek, C Arnold; van Zonneveld, Anton Jan; Reitsma, Pieter H; Hamming, Jaap F; de Boer, Hetty C; Versteeg, Henri H; Quax, Paul H A

2013-01-01

In collateral development (i.e. arteriogenesis), mononuclear cells are important and exist as a heterogeneous population consisting of pro-inflammatory and anti-inflammatory/repair-associated cells. Protease-activated receptor (PAR)1 and PAR2 are G-protein-coupled receptors that are both expressed by mononuclear cells and are involved in pro-inflammatory reactions, while PAR2 also plays a role in repair-associated responses. Here, we investigated the physiological role of PAR1 and PAR2 in arteriogenesis in a murine hind limb ischemia model. PAR1-deficient (PAR1-/-), PAR2-deficient (PAR2-/-) and wild-type (WT) mice underwent femoral artery ligation. Laser Doppler measurements revealed reduced post-ischemic blood flow recovery in PAR2-/- hind limbs when compared to WT, while PAR1-/- mice were not affected. Upon ischemia, reduced numbers of smooth muscle actin (SMA)-positive collaterals and CD31-positive capillaries were found in PAR2-/- mice when compared to WT mice, whereas these parameters in PAR1-/- mice did not differ from WT mice. The pool of circulating repair-associated (Ly6C-low) monocytes and the number of repair-associated (CD206-positive) macrophages surrounding collaterals in the hind limbs were increased in WT and PAR1-/- mice, but unaffected in PAR2-/- mice. The number of repair-associated macrophages in PAR2-/- hind limbs correlated with CD11b- and CD115-expression on the circulating monocytes in these animals, suggesting that monocyte extravasation and M-CSF-dependent differentiation into repair-associated cells are hampered. PAR2, but not PAR1, is involved in arteriogenesis and promotes the repair-associated response in ischemic tissues. Therefore, PAR2 potentially forms a new pro-arteriogenic target in coronary artery disease (CAD) patients.

Intravenous injection of indocyanine green results in an artificial transient desaturation by pulse oximetry.

PubMed

Ediriwickrema, Lilangi S; Francis, Jasmine H; Arslan-Carlon, Vittoria; Dalecki, Paul H; Brodie, Scott E; Marr, Brian P; Abramson, David H

2015-01-01

To describe a case series of transient oxygen desaturation measured by pulse oximetry during the intravenous infusion of indocyanine green to enhance transpupillary thermotherapy in treating retinoblastoma after ophthalmic artery chemosurgery. Retrospective descriptive case series. The intravenous administration of indocyanine green for ophthalmic angiography resulted in a transient drop in oxygen saturation as measured by Nellcor fingertip pulse oximetry in three children with retinoblastoma receiving indocyanine green-guided transpupillary thermotherapy. The magnitude of reduction ranged from 92% to 94% from an initial reading of 99% to 100% in each case, with an average duration of 3 minutes. Concurrent measurement of blood pressure, pulse, and expired CO2 showed no changes during this process. Administration of intravenous indocyanine green resulted in a transient desaturation by oximetry during transpupillary thermotherapy for children with retinoblastoma under anesthesia because of the fluorescent dye's absorption of red light in a manner similar to that of deoxygenated hemoglobin, thereby leading to transient instrument misinterpretation and miscalculation of arterial oxygenation.

Construction of the Helsinki University of Technology (HUT) pulsed positron beam

NASA Astrophysics Data System (ADS)

Fallström, K.; Laine, T.

1999-08-01

We are constructing a pulsed positron beam facility for lifetime measurements in thin surface layers. Our beam system comprises a 22Na positron source and a tungsten foil moderator followed by a prebuncher and a chopper. A double-drift buncher will compress the beam into 120-ps pulses at the target. The end energy of the positron beam can be adjusted between 3 keV and 30 keV by changing the potential of the source end of the beam. The bunching electronics and most of the beam guiding magnets are also floating at the high voltage. The sample is at ground potential to facilitate variable temperature measurements. With a test source of 6 mCi 22Na we get a prebunched beam intensity of 4×10 3 positrons per second in 1.5-ns wide pulses (the bunching frequency is 33.33 MHz). We are currently testing the chopper and the following buncher stages and building the final accelerator/decelerator system.

Phosphorylation of Mycobacterium tuberculosis ParB Participates in Regulating the ParABS Chromosome Segregation System

PubMed Central

Baronian, Grégory; Ginda, Katarzyna; Berry, Laurence; Cohen-Gonsaud, Martin; Zakrzewska-Czerwińska, Jolanta; Jakimowicz, Dagmara; Molle, Virginie

2015-01-01

Here, we present for the first time that Mycobacterium tuberculosis ParB is phosphorylated by several mycobacterial Ser/Thr protein kinases in vitro. ParB and ParA are the key components of bacterial chromosome segregation apparatus. ParB is a cytosolic conserved protein that binds specifically to centromere-like DNA parS sequences and interacts with ParA, a weak ATPase required for its proper localization. Mass spectrometry identified the presence of ten phosphate groups, thus indicating that ParB is phosphorylated on eight threonines, Thr32, Thr41, Thr53, Thr110, Thr195, and Thr254, Thr300, Thr303 as well as on two serines, Ser5 and Ser239. The phosphorylation sites were further substituted either by alanine to prevent phosphorylation or aspartate to mimic constitutive phosphorylation. Electrophoretic mobility shift assays revealed a drastic inhibition of DNA-binding by ParB phosphomimetic mutant compared to wild type. In addition, bacterial two-hybrid experiments showed a loss of ParA-ParB interaction with the phosphomimetic mutant, indicating that phosphorylation is regulating the recruitment of the partitioning complex. Moreover, fluorescence microscopy experiments performed in the surrogate Mycobacterium smegmatis ΔparB strain revealed that in contrast to wild type Mtb ParB, which formed subpolar foci similar to M. smegmatis ParB, phoshomimetic Mtb ParB was delocalized. Thus, our findings highlight a novel regulatory role of the different isoforms of ParB representing a molecular switch in localization and functioning of partitioning protein in Mycobacterium tuberculosis. PMID:25807382

Phosphorylation of Mycobacterium tuberculosis ParB participates in regulating the ParABS chromosome segregation system.

PubMed

Baronian, Grégory; Ginda, Katarzyna; Berry, Laurence; Cohen-Gonsaud, Martin; Zakrzewska-Czerwińska, Jolanta; Jakimowicz, Dagmara; Molle, Virginie

2015-01-01

Here, we present for the first time that Mycobacterium tuberculosis ParB is phosphorylated by several mycobacterial Ser/Thr protein kinases in vitro. ParB and ParA are the key components of bacterial chromosome segregation apparatus. ParB is a cytosolic conserved protein that binds specifically to centromere-like DNA parS sequences and interacts with ParA, a weak ATPase required for its proper localization. Mass spectrometry identified the presence of ten phosphate groups, thus indicating that ParB is phosphorylated on eight threonines, Thr32, Thr41, Thr53, Thr110, Thr195, and Thr254, Thr300, Thr303 as well as on two serines, Ser5 and Ser239. The phosphorylation sites were further substituted either by alanine to prevent phosphorylation or aspartate to mimic constitutive phosphorylation. Electrophoretic mobility shift assays revealed a drastic inhibition of DNA-binding by ParB phosphomimetic mutant compared to wild type. In addition, bacterial two-hybrid experiments showed a loss of ParA-ParB interaction with the phosphomimetic mutant, indicating that phosphorylation is regulating the recruitment of the partitioning complex. Moreover, fluorescence microscopy experiments performed in the surrogate Mycobacterium smegmatis ΔparB strain revealed that in contrast to wild type Mtb ParB, which formed subpolar foci similar to M. smegmatis ParB, phoshomimetic Mtb ParB was delocalized. Thus, our findings highlight a novel regulatory role of the different isoforms of ParB representing a molecular switch in localization and functioning of partitioning protein in Mycobacterium tuberculosis.

Protease-activated receptor 2 (PAR2) is upregulated by Acanthamoeba plasminogen activator (aPA) and induces proinflammatory cytokine in human corneal epithelial cells.

PubMed

Tripathi, Trivendra; Abdi, Mahshid; Alizadeh, Hassan

2014-05-29

Acanthamoeba plasminogen activator (aPA) is a serine protease elaborated by Acanthamoeba trophozoites that facilitates the invasion of trophozoites to the host and contributes to the pathogenesis of Acanthamoeba keratitis (AK). The aim of this study was to explore if aPA stimulates proinflammatory cytokine in human corneal epithelial (HCE) cells via the protease-activated receptors (PARs) pathway. Acanthamoeba castellanii trophozoites were grown in peptone-yeast extract glucose for 7 days, and the supernatants were collected and centrifuged. The aPA was purified using the fast protein liquid chromatography system, and aPA activity was determined by zymography assays. Human corneal epithelial cells were incubated with or without aPA (100 μg/mL), PAR1 agonists (thrombin, 10 μM; TRAP-6, 10 μM), and PAR2 agonists (SLIGRL-NH2, 100 μM; AC 55541, 10 μM) for 24 and 48 hours. Inhibition of PAR1 and PAR2 involved preincubating the HCE cells for 1 hour with the antagonist of PAR1 (SCH 79797, 60 μM) and PAR2 (FSLLRY-NH2, 100 μM) with or without aPA. Human corneal epithelial cells also were preincubated with PAR1 and PAR2 antagonists and then incubated with or without PAR1 agonists (thrombin and TRAP-6) and PAR2 agonists (SLIGRL-NH2 and AC 55541). Expression of PAR1 and PAR2 was examined by quantitative RT-PCR (qRT-PCR), flow cytometry, and immunocytochemistry. Interleukin-8 expression was quantified by qRT-PCR and ELISA. Human corneal epithelial cells constitutively expressed PAR1 and PAR2 mRNA. Acanthamoeba plasminogen activator and PAR2 agonists significantly upregulated PAR2 mRNA expression (1- and 2-fold, respectively) (P < 0.05). Protease-activated receptor 2 antagonist significantly inhibited aPA, and PAR2 agonists induced PAR2 mRNA expression in HCE cells (P < 0.05). Protease-activated receptor 1 agonists, but not aPA, significantly upregulated PAR1 mRNA expression, which was significantly inhibited by PAR1 antagonist in HCE cells. Acanthamoeba plasminogen activator and PAR2 agonists stimulated IL-8 mRNA expression and protein production, which is significantly diminished by PAR2 antagonist (P < 0.05). Protease-activated receptor 1 antagonist did not alter aPA-stimulated IL-8 mRNA expression and protein production in HCE cells. Flow cytometry and immunocytochemistry showed that aPA and SLIGRL-NH2 (PAR2 agonist) upregulated PAR2 surface protein as compared to that in unstimulated HCE cells. Thrombin, but not aPA, stimulated PAR1 surface protein in HCE cells. Acanthamoeba plasminogen activator specifically induces expression and production of IL-8 in HCE cells via PAR2 pathway, and PAR2 antagonists may be used as a therapeutic target in AK. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Urokinase Receptor Counteracts Vascular Smooth Muscle Cell Functional Changes Induced by Surface Topography

PubMed Central

Kiyan, Yulia; Kurselis, Kestutis; Kiyan, Roman; Haller, Hermann; Chichkov, Boris N.; Dumler, Inna

2013-01-01

Current treatments for human coronary artery disease necessitate the development of the next generations of vascular bioimplants. Recent reports provide evidence that controlling cell orientation and morphology through topographical patterning might be beneficial for bioimplants and tissue engineering scaffolds. However, a concise understanding of cellular events underlying cell-biomaterial interaction remains missing. In this study, applying methods of laser material processing, we aimed to obtain useful markers to guide in the choice of better vascular biomaterials. Our data show that topographically treated human primary vascular smooth muscle cells (VSMC) have a distinct differentiation profile. In particular, cultivation of VSMC on the microgrooved biocompatible polymer E-shell induces VSMC modulation from synthetic to contractile phenotype and directs formation and maintaining of cell-cell communication and adhesion structures. We show that the urokinase receptor (uPAR) interferes with VSMC behavior on microstructured surfaces and serves as a critical regulator of VSMC functional fate. Our findings suggest that microtopography of the E-shell polymer could be important in determining VSMC phenotype and cytoskeleton organization. They further suggest uPAR as a useful target in the development of predictive models for clinical VSMC phenotyping on functional advanced biomaterials. PMID:23843899

Conditioned Side Effects Induced by Cancer Chemotherapy: Prevention Through Behavioral Treatment.

ERIC Educational Resources Information Center

Burish, Thomas G.; And Others

1987-01-01

Studied cancer patients (N=24) in order to determine whether conditioned nausea and vomiting could be delayed or prevented. Indicated that patients receiving progressive muscle relaxation training and guided imagery had significantly less nausea and vomiting and significanty lower blood pressures, pulse rates, and dysphoria, especially anxiety,…

PH motifs in PAR1&2 endow breast cancer growth.

PubMed

Kancharla, A; Maoz, M; Jaber, M; Agranovich, D; Peretz, T; Grisaru-Granovsky, S; Uziely, B; Bar-Shavit, R

2015-11-24

Although emerging roles of protease-activated receptor1&2 (PAR1&2) in cancer are recognized, their underlying signalling events are poorly understood. Here we show signal-binding motifs in PAR1&2 that are critical for breast cancer growth. This occurs via the association of the pleckstrin homology (PH) domain with Akt/PKB as a key signalling event of PARs. Other PH-domain signal-proteins such as Etk/Bmx and Vav3 also associate with PAR1 and PAR2 through their PH domains. PAR1 and PAR2 bind with priority to Etk/Bmx. A point mutation in PAR2, H349A, but not in R352A, abrogates PH-protein association and is sufficient to markedly reduce PAR2-instigated breast tumour growth in vivo and placental extravillous trophoblast (EVT) invasion in vitro. Similarly, the PAR1 mutant hPar1-7A, which is unable to bind the PH domain, reduces mammary tumours and EVT invasion, endowing these motifs with physiological significance and underscoring the importance of these previously unknown PAR1 and PAR2 PH-domain-binding motifs in both pathological and physiological invasion processes.

Calibration of a speckle-based compressive sensing receiver

NASA Astrophysics Data System (ADS)

Sefler, George A.; Shaw, T. Justin; Stapleton, Andrew D.; Valley, George C.

2017-02-01

Optical speckle in a multimode waveguide has been proposed to perform the function of a compressive sensing (CS) measurement matrix (MM) in a receiver for GHz-band radio frequency (RF) signals. Unlike other devices used for the CS MM, e.g. the digital micromirror device (DMD) used in the single pixel camera, the elements of the speckle MM are not known before use and must be measured and calibrated. In our system, the RF signal is modulated on a repetitively pulsed chirped wavelength laser source, generated from mode-locked laser pulses that have been dispersed in time or from an electrically addressed distributed Bragg reflector laser. Next, the optical beam with RF propagates through a multimode fiber or waveguide, which applies different weights in wavelength (or equivalently time) and space and performs the function of the CS MM. The output of the guide is directed to or imaged on a bank of photodiodes with integration time set to the pulse length of the chirp waveform. The output of each photodiode is digitized by an analog-to-digital converter (ADC), and the data from these ADCs are used to form the CS measurement vector. Accurate recovery of the RF signal from CS measurements depends critically on knowledge of the weights in the MM. Here we present results using a stable wavelength laser source to probe the guide.

New description of charged particle propagation in random magnetic fields

NASA Technical Reports Server (NTRS)

Earl, James A.

1994-01-01

When charged particles spiral along a large constant magnetic field, their trajectories are scattered by random components that are superposed on the guiding field. In the simplest analysis of this situation, scattering causes the particles to diffuse parallel to the guiding field. At the next level of approximation, moving pulses that correspond to a coherent mode of propagation are present, but they are represented by delta-functions whose infinitely narrow width makes no sense physically and is inconsistent with the finite duration of coherent pulses observed in solar energetic particle events. To derive a more realistic description, the transport problem is formulated in terms of 4 x 4 matrices, which derive from a representation of the particle distribution function in terms of eigenfunctions of the scattering operator, and which lead to useful approximations that give explicit predictions of the detailed evolution not only of the coherent pulses, but also of the diffusive wake. More specifically, the new description embodies a simple convolution of a narrow Gaussian with the solutions above that involve delta-functions, but with a slightly reduced coherent velocity. The validity of these approximations, which can easily be calculated on a desktop computer, has been exhaustively confirmed by comparison with results of Monte Carlo simulations which kept track of 50 million particles and which were carried out on the Maspar computer at Goddard Space Flight Center.

Guide to the Construction of a Simple 1500 C Test Furnace. Revision

DTIC Science & Technology

1983-01-01

A.v e ~1 ue , ’..J -3- ~h i n~,;tor , [)( 20a:p. .. ·HTr~ : 0. Grove $ :~ . r~ . ~.p ;~ir;gs ~l o . of Copies. To ~~Liond l Scrence Foundat ioo...a~-. r~. !.indley ArRese<n·ch Manuf acturi ng Company , AiRe~earOr Cas t ing Company, ?s;~, Wr st ! 90th <,treet, Torrance, CA 90S05 .~TTN : Mr...Tec hnol ogy, De par t men t of i"P to 1 I.Jrgy and Mater i a ls Science , Cambri dge, MA 02139 ATTN : Prof . R. L. Cob l e Prof. H. K. Bowen

Protease-Activated Receptor 4 (PAR4): A Promising Target for Antiplatelet Therapy.

PubMed

Rwibasira Rudinga, Gamariel; Khan, Ghulam Jilany; Kong, Yi

2018-02-14

Cardiovascular diseases (CVDs) are currently among the leading causes of death worldwide. Platelet aggregation is a key cellular component of arterial thrombi and major cause of CVDs. Protease-activated receptors (PARs), including PAR1, PAR2, PAR3 and PAR4, fall within a subfamily of seven-transmembrane G-protein-coupled receptors (GPCR). Human platelets express PAR1 and PAR4, which contribute to the signaling transduction processes. In association with CVDs, PAR4 not only contributes to platelet activation but also is a modulator of cellular responses that serve as hallmarks of inflammation. Although several antiplatelet drugs are available on the market, they have many side effects that limit their use. Emerging evidence shows that PAR4 targeting is a safer strategy for preventing thrombosis and consequently may improve the overall cardiac safety profile. Our present review summarizes the PAR4 structural characteristics, activation mechanism, role in the pathophysiology of diseases and understanding the association of PAR4 targeting for improved cardiac protection. Conclusively, this review highlights the importance of PAR4 antagonists and its potential utility in different CVDs.

A magnetic flux leakage and magnetostrictive guided wave hybrid transducer for detecting bridge cables.

PubMed

Xu, Jiang; Wu, Xinjun; Cheng, Cheng; Ben, Anran

2012-01-01

Condition assessment of cables has gained considerable attention for the bridge safety. A magnetic flux leakage and magnetostrictive guided wave hybrid transducer is provided to inspect bridge cables. The similarities and differences between the two methods are investigated. The hybrid transducer for bridge cables consists of an aluminum framework, climbing modules, embedded magnetizers and a ribbon coil. The static axial magnetic field provided by the magnetizers meets the needs of the magnetic flux leakage testing and the magnetostrictive guided wave testing. The magnetizers also provide the attraction for the climbing modules. In the magnetic flux leakage testing for the free length of cable, the coil induces the axial leakage magnetic field. In the magnetostrictive guided wave testing for the anchorage zone, the coil provides a pulse high power variational magnetic field for generating guided waves; the coil induces the magnetic field variation for receiving guided waves. The experimental results show that the transducer with the corresponding inspection system could be applied to detect the broken wires in the free length and in the anchorage zone of bridge cables.

A Magnetic Flux Leakage and Magnetostrictive Guided Wave Hybrid Transducer for Detecting Bridge Cables

PubMed Central

Xu, Jiang; Wu, Xinjun; Cheng, Cheng; Ben, Anran

2012-01-01

Condition assessment of cables has gained considerable attention for the bridge safety. A magnetic flux leakage and magnetostrictive guided wave hybrid transducer is provided to inspect bridge cables. The similarities and differences between the two methods are investigated. The hybrid transducer for bridge cables consists of an aluminum framework, climbing modules, embedded magnetizers and a ribbon coil. The static axial magnetic field provided by the magnetizers meets the needs of the magnetic flux leakage testing and the magnetostrictive guided wave testing. The magnetizers also provide the attraction for the climbing modules. In the magnetic flux leakage testing for the free length of cable, the coil induces the axial leakage magnetic field. In the magnetostrictive guided wave testing for the anchorage zone, the coil provides a pulse high power variational magnetic field for generating guided waves; the coil induces the magnetic field variation for receiving guided waves. The experimental results show that the transducer with the corresponding inspection system could be applied to detect the broken wires in the free length and in the anchorage zone of bridge cables. PMID:22368483

Acute effects of pulsed-laser irradiation on the arterial wall

NASA Astrophysics Data System (ADS)

Nakamura, Fumitaka; Kvasnicka, Jan; Lu, Hanjiang; Geschwind, Herbert J.; Levame, Micheline; Bousbaa, Hassan; Lange, Francoise

1992-08-01

Pulsed laser coronary angioplasty with an excimer or a holmium-yttrium-aluminum-garnet (Ho:YAG) laser may become an alternative treatment for patients with coronary artery disease. However, little is known about its acute consequences on the normal arterial wall. This study was designed to examine the acute histologic consequences of these two pulsed lasers on the arterial wall of normal iliac arteries in rabbits. Irradiation with each laser was performed in 15 normal iliac sites on eight male New Zealand white rabbits. The excimer laser was operated at 308 nm, 25 Hz, 50 mJ/mm2/pulse, and 135 nsec/pulse and the Ho:YAG laser was operated at 2.1 micrometers , 3/5 Hz, 400 mJ/pulse, and 250 microsecond(s) ec/pulse. The excimer and Ho:YAG laser were coupled into a multifiber wire-guided catheter of 1.4 and 1.5 mm diameter, respectively. The sites irradiated with excimer or Ho:YAG laser had the same kinds of histologic features, consisting of exfoliation of the endothelium, disorganization of internal elastic lamina, localized necrosis of vascular smooth muscle cells, and fissures in the medial layer. However, the sites irradiated with excimer laser had lower grading scores than those irradiated with Ho:YAG laser (p < 0.05). Laser irradiation with excimer or Ho:YAG laser of normal arteries results in localized mechanical vascular injury.

Mining CRRES IDM Pulse Data and CRRES Environmental Data to Improve Spacecraft Charging/Discharging Models and Guidelines

NASA Technical Reports Server (NTRS)

Brautigam, D. H.; Frederickson, A. R.

2004-01-01

One can truly predict the charging and pulsing in space over a year's time using only the physics that worked for periods of an hour and less in prior publications. All portions of the task were achieved, including the optional portion of determining a value for conductivity that best .t the data. Fortran statements were developed that are required for the NUMIT runs to work with this kind of data from space. In addition to developing the Fortran for NUMIT, simple correlations between the IDM pulsing history and the space radiation were observed because we now have a better characterization of the space radiation. The study showed that: (1) the new methods for measurement of charge storage and conduction in insulators provide the correct values to use for prediction of charging and pulsing in space; (2) the methods in NUMIT that worked well for time durations less than hours now work well for durations of months; (3) an average spectrum such as AE8 is probably not a good guide for predicting pulsing in space one must take time dependence into account in order to understand insulator pulsing; and (4) the old method for predicting pulse rates in space that was based on the CRRES data could be improved to include dependencies on material parameters.

Treatment of Refractory Idiopathic Supraorbital Neuralgia Using Percutaneous Pulsed Radiofrequency.

PubMed

Luo, Fang; Lu, Jingjing; Ji, Nan

2018-02-26

No ideal therapeutic method currently exists for refractory idiopathic supraorbital neuralgia patients who do not respond to conservative therapy, including medications and nerve blocks. Pulsed radiofrequency is a neuromodulation technique that does not produce sequelae of nerve damage after treatment. However, the efficacy of percutaneous pulsed radiofrequency for the treatment of refractory idiopathic supraorbital neuralgia is still not clear. The purpose of our study was to evaluate the efficacy and safety of pulsed radiofrequency treatment of the supraorbital nerve for refractory supraorbital neuralgia patients. We prospectively investigated the long-term effects of ultrasound-guided percutaneous pulsed radiofrequency in the treatment of 22 refractory idiopathic supraorbital neuralgia patients. A reduction in the verbal pain numeric rating scale score of more than 50% was used as the standard of effectiveness. The effectiveness rates at different time points within 2 years were calculated. After a single pulsed radiofrequency treatment, the effectiveness rate at 1 and 3 months was 77%, and the rates at 6 months, 1 year, and 2 years were 73%, 64%, and 50%, respectively. Except for a small portion of patients (23%) who experienced mild upper eyelid ecchymosis that gradually disappeared after approximately 2 weeks, no obvious complications were observed. In conclusion, the results of our study demonstrate that for patients with refractory idiopathic supraorbital neuralgia, percutaneous pulsed radiofrequency may be an effective and safe treatment choice. © 2018 World Institute of Pain.

Non-periodic multi-slit masking for a single counter rotating 2-disc chopper and channeling guides for high resolution and high intensity neutron TOF spectroscopy

NASA Astrophysics Data System (ADS)

Bartkowiak, M.; Hofmann, T.; Stüßer, N.

2017-02-01

Energy resolution is an important design goal for time-of-flight instruments and neutron spectroscopy. For high-resolution applications, it is required that the burst times of choppers be short, going down to the μs-range. To produce short pulses while maintaining high neutron flux, we propose beam masks with more than two slits on a counter-rotating 2-disc chopper, behind specially adapted focusing multi-channel guides. A novel non-regular arrangement of the slits ensures that the beam opens only once per chopper cycle, when the masks are congruently aligned. Additionally, beam splitting and intensity focusing by guides before and after the chopper position provide high intensities even for small samples. Phase-space analysis and Monte Carlo simulations on examples of four-slit masks with adapted guide geometries show the potential of the proposed setup.

Systematic neutron guide misalignment for an accelerator-driven spallation neutron source

NASA Astrophysics Data System (ADS)

Zendler, C.; Bentley, P. M.

2016-08-01

The European Spallation Source (ESS) is a long pulse spallation neutron source that is currently under construction in Lund, Sweden. A considerable fraction of the 22 planned instruments extend as far as 75-150 m from the source. In such long beam lines, misalignment between neutron guide segments can decrease the neutron transmission significantly. In addition to a random misalignment from installation tolerances, the ground on which ESS is built can be expected to sink with time, and thus shift the neutron guide segments further away from the ideal alignment axis in a systematic way. These systematic errors are correlated to the ground structure, position of buildings and shielding installation. Since the largest deformation is expected close to the target, even short instruments might be noticeably affected. In this study, the effect of this systematic misalignment on short and long ESS beam lines is analyzed, and a possible mitigation by overillumination of subsequent guide sections investigated.

Proteinase-Activated Receptor-1 and Immunomodulatory Effects of a PAR1-Activating Peptide in a Mouse Model of Prostatitis

PubMed Central

Stanton, M. Mark; Nelson, Lisa K.; Benediktsson, Hallgrimur; Hollenberg, Morley D.; Buret, Andre G.; Ceri, Howard

2013-01-01

Background. Nonbacterial prostatitis has no established etiology. We hypothesized that proteinase-activated receptor-1 (PAR1) can play a role in prostatitis. We therefore investigated the effects of PAR1 stimulation in the context of a new model of murine nonbacterial prostatitis. Methods. Using a hapten (ethanol-dinitrobenzene sulfonic acid- (DNBS-)) induced prostatitis model with both wild-type and PAR1-null mice, we examined (1) the location of PAR1 in the mouse prostate and (2) the impact of a PAR1-activating peptide (TFLLR-NH2: PAR1-TF) on ethanol-DNBS-induced inflammation. Results. Ethanol-DNBS-induced inflammation was maximal at 2 days. In the tissue, PAR1 was expressed predominantly along the apical acini of prostatic epithelium. Although PAR1-TF on its own did not cause inflammation, its coadministration with ethanol-DNBS reduced all indices of acute prostatitis. Further, PAR1-TF administration doubled the prostatic production of interleukin-10 (IL-10) compared with ethanol-DNBS treatment alone. This enhanced IL-10 was not observed in PAR1-null mice and was not caused by the reverse-sequence receptor-inactive peptide, RLLFT-NH2. Surprisingly, PAR1-TF, also diminished ethanol-DNBS-induced inflammation in PAR1-null mice. Conclusions. PAR1 is expressed in the mouse prostate and its activation by PAR1-TF elicits immunomodulatory effects during ethanol-DNBS-induced prostatitis. However, PAR1-TF also diminishes ethanol-DNBS-induced inflammation via a non-PAR1 mechanism by activating an as-yet unknown receptor. PMID:24459330

The Utilization of Robotic Pets in Dementia Care.

PubMed

Petersen, Sandra; Houston, Susan; Qin, Huanying; Tague, Corey; Studley, Jill

2017-01-01

Behavioral problems may affect individuals with dementia, increasing the cost and burden of care. Pet therapy has been known to be emotionally beneficial for many years. Robotic pets have been shown to have similar positive effects without the negative aspects of traditional pets. Robotic pet therapy offers an alternative to traditional pet therapy. The study rigorously assesses the effectiveness of the PARO robotic pet, an FDA approved biofeedback device, in treating dementia-related symptoms. A randomized block design with repeated measurements guided the study. Before and after measures included reliable, valid tools such as: RAID, CSDD, GDS, pulse rate, pulse oximetry, and GSR. Participants interacted with the PARO robotic pet, and the control group received standard activity programs. Five urban secure dementia units comprised the setting. 61 patients, with 77% females, average 83.4 years in age, were randomized into control and treatment groups. Compared to the control group, RAID, CSDD, GSR, and pulse oximetry were increased in the treatment group, while pulse rate, pain medication, and psychoactive medication use were decreased. The changes in GSR, pulse oximetry, and pulse rate over time were plotted for both groups. The difference between groups was consistent throughout the 12-week study for pulse oximetry and pulse rate, while GSR had several weeks when changes were similar between groups. Treatment with the PARO robot decreased stress and anxiety in the treatment group and resulted in reductions in the use of psychoactive medications and pain medications in elderly clients with dementia.

The Utilization of Robotic Pets in Dementia Care

PubMed Central

Petersen, Sandra; Houston, Susan; Qin, Huanying; Tague, Corey; Studley, Jill

2016-01-01

Background: Behavioral problems may affect individuals with dementia, increasing the cost and burden of care. Pet therapy has been known to be emotionally beneficial for many years. Robotic pets have been shown to have similar positive effects without the negative aspects of traditional pets. Robotic pet therapy offers an alternative to traditional pet therapy. Objective: The study rigorously assesses the effectiveness of the PARO robotic pet, an FDA approved biofeedback device, in treating dementia-related symptoms. Methods: A randomized block design with repeated measurements guided the study. Before and after measures included reliable, valid tools such as: RAID, CSDD, GDS, pulse rate, pulse oximetry, and GSR. Participants interacted with the PARO robotic pet, and the control group received standard activity programs. Five urban secure dementia units comprised the setting. Results: 61 patients, with 77% females, average 83.4 years in age, were randomized into control and treatment groups. Compared to the control group, RAID, CSDD, GSR, and pulse oximetry were increased in the treatment group, while pulse rate, pain medication, and psychoactive medication use were decreased. The changes in GSR, pulse oximetry, and pulse rate over time were plotted for both groups. The difference between groups was consistent throughout the 12-week study for pulse oximetry and pulse rate, while GSR had several weeks when changes were similar between groups. Conclusions: Treatment with the PARO robot decreased stress and anxiety in the treatment group and resulted in reductions in the use of psychoactive medications and pain medications in elderly clients with dementia. PMID:27716673

Symmetry breaking and polarization of the C. elegans zygote by the polarity protein PAR-2.

PubMed

Zonies, Seth; Motegi, Fumio; Hao, Yingsong; Seydoux, Geraldine

2010-05-01

Polarization of the C. elegans zygote is initiated by ECT-2-dependent cortical flows, which mobilize the anterior PAR proteins (PAR-3, PAR-6 and PKC-3) away from the future posterior end of the embryo marked by the sperm centrosome. Here, we demonstrate the existence of a second, parallel and redundant pathway that can polarize the zygote in the absence of ECT-2-dependent cortical flows. This second pathway depends on the polarity protein PAR-2. We show that PAR-2 localizes to the cortex nearest the sperm centrosome even in the absence of cortical flows. Once on the cortex, PAR-2 antagonizes PAR-3-dependent recruitment of myosin, creating myosin flows that transport the anterior PAR complex away from PAR-2 in a positive-feedback loop. We propose that polarity in the C. elegans zygote is initiated by redundant ECT-2- and PAR-2-dependent mechanisms that lower PAR-3 levels locally, triggering a positive-feedback loop that polarizes the entire cortex.

The DNA binding parvulin Par17 is targeted to the mitochondrial matrix by a recently evolved prepeptide uniquely present in Hominidae

PubMed Central

Kessler, Daniel; Papatheodorou, Panagiotis; Stratmann, Tina; Dian, Elke Andrea; Hartmann-Fatu, Cristina; Rassow, Joachim; Bayer, Peter; Mueller, Jonathan Wolf

2007-01-01

Background The parvulin-type peptidyl prolyl cis/trans isomerase Par14 is highly conserved in all metazoans. The recently identified parvulin Par17 contains an additional N-terminal domain whose occurrence and function was the focus of the present study. Results Based on the observation that the human genome encodes Par17, but bovine and rodent genomes do not, Par17 exon sequences from 10 different primate species were cloned and sequenced. Par17 is encoded in the genomes of Hominidae species including humans, but is absent from other mammalian species. In contrast to Par14, endogenous Par17 was found in mitochondrial and membrane fractions of human cell lysates. Fluorescence of EGFP fusions of Par17, but not Par14, co-localized with mitochondrial staining. Par14 and Par17 associated with isolated human, rat and yeast mitochondria at low salt concentrations, but only the Par17 mitochondrial association was resistant to higher salt concentrations. Par17 was imported into mitochondria in a time and membrane potential-dependent manner, where it reached the mitochondrial matrix. Moreover, Par17 was shown to bind to double-stranded DNA under physiological salt conditions. Conclusion Taken together, the DNA binding parvulin Par17 is targeted to the mitochondrial matrix by the most recently evolved mitochondrial prepeptide known to date, thus adding a novel protein constituent to the mitochondrial proteome of Hominidae. PMID:17875217

Response of carnation (Dianthus caryophyllus) cultivars to different postharvest preservatives.

PubMed

Adugna, Biniam; Belew, Derbew; Kassa, Negussie

2013-10-01

Experiments were conducted to assess the effect of selected pulsing solutions on the days to flower bud shrinkage, leaf wilting and petal edge drying occurrence of carnation cultivars (Green-Go and Galy). The pulsing solutions used for this investigation were Silver Thiosulfate (STS) (0.2, 0.6, 1 mM) and also ethanol (6, 8, 10%), both received equal amount of sucrose (10%). Besides, to simulate the actual practice of the farm (0.4 mM Silver Thiosulfate (STS) plus 0.3 mM T.O.G) was used as a standard control. Senescence symptoms such as flower bud shrinkage, petal edge drying and leaf wilting were monitored. The results obtained showed that 1 mM STS plus 25 g sucrose achieved rapid petal edge drying for Green-Go cultivar. On the other hand, positive effects were also observed in days to flower bud shrinkage extended by 6 mM Silver Thiosulfate (STS) plus 25 g sucrose and being in par with 8% ethanol plus 25 g sucrose for Green-Go cultivar. Subsequently, the standard control, 0.6 mM Silver Thiosulfate (STS) plus 25 g sucrose and 8% ethanol plus 25 g sucrose attended comparable increment on the days to leaf wilting occurrences.

Photonic Switching Devices Using Light Bullets

NASA Technical Reports Server (NTRS)

Goorjian, Peter M. (Inventor)

1997-01-01

The present invention is directed toward a unique ultra-fast, all-optical switching device or switch made with readily available, relatively inexpensive, highly nonlinear photonic glasses. These photonic glasses have a sufficiently negative group velocity dispersion and high nonlinear index of refraction to support stable light bullets. The light bullets counterpropagate through, and interact within the waveguide to selectively change each others' directions of propagation into predetermined channels. In one embodiment, the switch utilizes a rectangularly planar slab waveguide, and further includes two central channels and a plurality of lateral channels for guiding the light bullets into and out of the waveguide. One advantage presented by the present all-optical switching device lies in its practical use of light bullets, thus preventing the degeneration of the pulses due to dispersion and diffraction at the front and back of the pulses. Another feature of the switching device is the relative insensitivity of the collision process to the time difference in which the counter-propagating pulses enter the waveguide. since. contrary to conventional co-propagating spatial solitons, the relative phase of the colliding pulses does not affect the interaction of these pulses. Yet another feature of the present all-optical switching device is the selection of the light pulse parameters which enables the generation of light bullets in highly nonlinear glasses.

Graphene-doped polymer nanofibers for low-threshold nonlinear optical waveguiding

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

Meng, Chao; Yu, Shao-Liang; Wang, Hong -Qing

Graphene-doped polymer nanofibers are fabricated by taper drawing of solvated polyvinyl alcohol doped with liquid-phase exfoliated graphene flakes. Nanofibers drawn this way typically have diameters measured in hundreds of nanometers and lengths in tens of millimeters; they show excellent uniformity and surface smoothness for optical waveguiding. Owing to their tightly confined waveguiding behavior, light–matter interaction in these subwavelength-diameter nanofibers is significantly enhanced. Using approximately 1350-nm-wavelength femto-second pulses, we demonstrate saturable absorption behavior in these nanofibers with a saturation threshold down to 0.25 pJ pulse -1 (peak power ~1.3 W). Additionally, using 1064-nm-wavelength nanosecond pulses as switching light, we show all-opticalmore » modulation of a 1550-nm-wavelength signal light guided along a single nanofiber with a switching peak power of ~3.2 W.« less

Measurement and Modeling of Dispersive Pulse Propagation in Drawn Wire Waveguides

NASA Technical Reports Server (NTRS)

Madaras, Eric I.; Kohl, Thomas W.; Rogers, Wayne P.

1995-01-01

An analytical model of dispersive pulse propagation in semi-infinite cylinders due to transient axially symmetric end conditions has been experimentally investigated. Specifically, the dispersive propagation of the first axially symmetric longitudinal mode in thin wire waveguides, which have ends in butt contact with longitudinal piezoelectric ultrasonic transducers, is examined. The method allows for prediction of a propagated waveform given a measured source waveform, together with the material properties of the cylinder. Alternatively, the source waveform can be extracted from measurement of the propagated waveform. The material properties required for implementation of the pulse propagation model are determined using guided wave phase velocity measurements. Hard tempered aluminum 1100 and 304 stainless steel wires, with 127, 305, and 406 micron diam., were examined. In general, the drawn wires were found to behave as transversely isotropic media.

Measurement and modeling of dispersive pulse propagation in draw wire waveguides

NASA Technical Reports Server (NTRS)

Madaras, Eric I.; Kohl, Thomas W.; Rogers, Wayne P.

1995-01-01

An analytical model of dispersive pulse propagation in semi-infinite cylinders due to transient axially symmetric end conditions has been experimentally investigated. Specifically, the dispersive propagation of the first axially symmetric longitudinal mode in thin wire waveguides, which have ends in butt contact with longitudinal piezoelectric ultrasonic transducers, is examined. The method allows for prediction of a propagated waveform given a measured source waveform, together with the material properties of the cylinder. Alternatively, the source waveform can be extracted from measurement of the propagated waveform. The material properties required for implementation of the pulse propagation model are determined using guided wave phase velocity measurements. Hard tempered aluminum 1100 and 304 stainless steel wires, with 127, 305, and 406 micron diam., were examined. In general, the drawn wires were found to behave as transversely isotropic media.

Graphene-doped polymer nanofibers for low-threshold nonlinear optical waveguiding

DOE PAGES

Meng, Chao; Yu, Shao-Liang; Wang, Hong -Qing; ...

2015-11-06

Graphene-doped polymer nanofibers are fabricated by taper drawing of solvated polyvinyl alcohol doped with liquid-phase exfoliated graphene flakes. Nanofibers drawn this way typically have diameters measured in hundreds of nanometers and lengths in tens of millimeters; they show excellent uniformity and surface smoothness for optical waveguiding. Owing to their tightly confined waveguiding behavior, light–matter interaction in these subwavelength-diameter nanofibers is significantly enhanced. Using approximately 1350-nm-wavelength femto-second pulses, we demonstrate saturable absorption behavior in these nanofibers with a saturation threshold down to 0.25 pJ pulse -1 (peak power ~1.3 W). Additionally, using 1064-nm-wavelength nanosecond pulses as switching light, we show all-opticalmore » modulation of a 1550-nm-wavelength signal light guided along a single nanofiber with a switching peak power of ~3.2 W.« less

A Miniature Forward-imaging B-scan Optical Coherence Tomography Probe to Guide Real-time Laser Ablation

PubMed Central

Li, Zhuoyan; Shen, Jin H.; Kozub, John A.; Prasad, Ratna; Lu, Pengcheng; Joos, Karen M.

2014-01-01

Background and Objective Investigations have shown that pulsed lasers tuned to 6.1 μm in wavelength are capable of ablating ocular and neural tissue with minimal collateral damage. This study investigated whether a miniature B-scan forward-imaging optical coherence tomography (OCT) probe can be combined with the laser to provide real-time visual feedback during laser incisions. Study Design/Methods and Materials A miniature 25-gauge B-scan forward-imaging OCT probe was developed and combined with a 250 μm hollow-glass waveguide to permit delivery of 6.1 μm laser energy. A gelatin mixture and both porcine corneal and retinal tissues were simultaneously imaged and lased (6.1 μm, 10 Hz, 0.4-0.7 mJ) through air. The ablation studies were observed and recorded in real time. The crater dimensions were measured using OCT imaging software (Bioptigen, Durham, NC). Histological analysis was performed on the ocular tissues. Results The combined miniature forward-imaging OCT and mid-infrared laser-delivery probe successfully imaged real-time tissue ablation in gelatin, corneal tissue, and retinal tissue. Application of a constant number of 60 pulses at 0.5 mJ/pulse to the gelatin resulted in a mean crater depth of 123 ± 15 μm. For the corneal tissue, there was a significant correlation between the number of pulses used and depth of the lased hole (Pearson correlation coefficient = 0.82; P = 0.0002). Histological analysis of the cornea and retina tissues showed discrete holes with minimal thermal damage. Conclusions A combined miniature OCT and laser -delivery probe can monitor real-time tissue laser ablation. With additional testing and improvements, this novel instrument has the future possibility of effectively guiding surgeries by simultaneously imaging and ablating tissue. PMID:24648326

Tantalum pentoxide waveguides and microresonators for VECSEL based frequency combs

NASA Astrophysics Data System (ADS)

Chen Sverre, T.; Woods, J. R. C.; Shaw, E. A.; Hua, Ping; Apostolopoulos, V.; Wilkinson, J. S.; Tropper, A. C.

2018-02-01

Tantalum pentoxide (Ta2O5) is a promising material for mass-producible, multi-functional, integrated photonics circuits on silicon, exhibiting robust electrical, mechanical and thermal properties, as well as good CMOS compatibility. In addition, Ta2O5 has been reported to demonstrate a non-linear response comparable to that of chalcogenide glass, in the region of 3-6 times larger than that of materials such as silica (SiO2) or silicon nitride (Si3N4). In contrast to Si-based dielectrics, it will accept trivalent ytterbium and erbium dopant ions, opening the possibility of on-chip amplification. The high refractive index of Ta2O5 is consistent with small guided mode cross-section area, and allows the construction of micro-ring resonators. Propagation losses as low as 0.2 dB=cm have been reported. In this paper we describe the design of a planar Ta2O5 waveguides optimised for the generation of coherent continuum with near infrared pulse trains at kW peak powers. The Pulse Repetition Frequency (PRF) of the VECSEL can be tuned to a sub-harmonic of the planar micro-ring and the optical pump power applied to the VECSEL can be adjusted so that mode-matching of the VECSEL pulse train with the micro-ring resonator can be achieved. We shall describe the fabrication of Ta2O5 guiding structures, and the characterisation of their nonlinear and other optical properties. Characterisation with conventional lasers will be used to assess the degree of coherent spectral broadening likely to be achievable using these devices when driven by mode-locked VECSELs operating near the current state-of- art for pulse energy and duration.

Optical coherence tomography (OCT) guided smart laser knife for cancer surgery (Conference Presentation)

NASA Astrophysics Data System (ADS)

Katta, Nitesh; Mcelroy, Austin; Estrada, Arnold; Milner, Thomas E.

2017-02-01

Neurological cancer surgeries require specialized tools that enhance imaging for precise cutting and removal of tissue without damaging adjacent neurological structures. The novel combination of high-resolution fast optical coherence tomography (OCT) alongside short pulsed nanosecond thulium (Tm) lasers offers stark advantages utilizing the superior beam quality, high volumetric tissue removal rates of thulium lasers with minimal residual thermal footprint in the tissue and avoiding damage to delicate sub-surface structures (e.g., nerves and microvessels); which has not been showcased before. A bench-top system is constructed, using a 15W 1940nm nanosecond pulsed Tm fiber laser (500uJ pulse energy, 100ns pulse duration, 30kHz repetition rate) for removing tissue and a swept source laser (1310±70nm, 100kHz sweep rate) is utilized for OCT imaging, forming a combined Tm/OCT system - a smart laser knife. The OCT image-guidance informs the Tm laser for cutting/removal of targeted tissue structures. Tissue phantoms were constructed to demonstrate surgical incision with blood vessel avoidance on the surface where 2mm wide 600um deep cuts are executed around the vessel using OCT to guide the procedure. Cutting up to delicate subsurface blood vessels (2mm deep) is demonstrated while avoiding damage to their walls. A tissue removal rate of 5mm^3/sec is obtained from the bench-top system. We constructed a blow-off model to characterize Tm cut depths taking into account the absorption coefficients and beam delivery systems to compute Arrhenius damage integrals. The model is used to compare predicted tissue removal rate and residual thermal injury with experimental values in response to Tm laser-tissue modification.

Techniques for measuring intercepted and absorbed PAR in corn canopies

NASA Technical Reports Server (NTRS)

Gallo, K. P.; Daughtry, C. S. T.

1984-01-01

The quantity of radiation potentially available for photosynthesis that is captured by the crop is best described as absorbed photosynthetically active radiation (PAR). Absorbed PAR (APAR) is the difference between descending and ascending fluxes. The four components of APAR were measured above and within two planting densities of corn (Zea mays L.) and several methods of measuring and estimating APAR were examined. A line quantum sensor that spatially averages the photosynthetic photon flux density provided a rapid and portable method of measuring APAR. PAR reflectance from the soil (Typic Argiaquoll) surface decreased from 10% to less than 1% of the incoming PAR as the canopy cover increased. PAR reflectance from the canopy decreased to less than 3% at maximum vegetative cover. Intercepted PAR (1 - transmitted PAR) generally overestimated absorbed PAR by less than 4% throughout most of the growing season. Thus intercepted PAR appears to be a reasonable estimate of absorbed PAR.

Role of the parCBA Operon of the Broad-Host-Range Plasmid RK2 in Stable Plasmid Maintenance

PubMed Central

Easter, Carla L.; Schwab, Helmut; Helinski, Donald R.

1998-01-01

The par region of the stably maintained broad-host-range plasmid RK2 is organized as two divergent operons, parCBA and parDE, and a cis-acting site. parDE encodes a postsegregational killing system, and parCBA encodes a resolvase (ParA), a nuclease (ParB), and a protein of unknown function (ParC). The present study was undertaken to further delineate the role of the parCBA region in the stable maintenance of RK2 by first introducing precise deletions in the three genes and then assessing the abilities of the different constructs to stabilize RK2 in three strains of Escherichia coli and two strains of Pseudomonas aeruginosa. The intact parCBA operon was effective in stabilizing a conjugation-defective RK2 derivative in E. coli MC1061K and RR1 but was relatively ineffective in E. coli MV10Δlac. In the two strains in which the parCBA operon was effective, deletions in parB, parC, or both parB and parC caused an approximately twofold reduction in the stabilizing ability of the operon, while a deletion in the parA gene resulted in a much greater loss of parCBA activity. For P. aeruginosa PAO1161Rifr, the parCBA operon provided little if any plasmid stability, but for P. aeruginosa PAC452Rifr, the RK2 plasmid was stabilized to a substantial extent by parCBA. With this latter strain, parA and res alone were sufficient for stabilization. The cer resolvase system of plasmid ColE1 and the loxP/Cre system of plasmid P1 were tested in comparison with the parCBA operon. We found that, not unlike what was previously observed with MC1061K, cer failed to stabilize the RK2 plasmid with par deletions in strain MV10Δlac, but this multimer resolution system was effective in stabilizing the plasmid in strain RR1. The loxP/Cre system, on the other hand, was very effective in stabilizing the plasmid in all three E. coli strains. These observations indicate that the parA gene, along with its res site, exhibits a significant level of plasmid stabilization in the absence of the parC and parB genes but that in at least one E. coli strain, all three genes are required for maximum stabilization. It cannot be determined from these results whether or not the stabilization effects seen with parCBA or the cer and loxP/Cre systems are strictly due to a reduction in the level of RK2 dimers and an increase in the number of plasmid monomer units or if these systems play a role in a more complex process of plasmid stabilization that requires as an essential step the resolution of plasmid dimers. PMID:9811663

Expression of proteinase-activated receptor (PAR)-2 in monocytes from allergic patients and potential molecular mechanism.

PubMed

Ge, Shuqing; Li, Tao; Yao, Qijian; Yan, Hongling; Huiyun, Zhang; Zheng, Yanshan; Zhang, Bin; He, Shaoheng

2016-12-01

Serine proteases play an important role in inflammation via PARs. However, little is known of expression levels of PARs on monocytes of allergic patients, and influence of serine proteases and PARs on TNF-α secretion from monocytes. Using quantitative real-time PCR (qPCR) and flowcytometry techniques, we observed that the expression level of PAR-2 in monocytes of patients with allergic rhinitis and asthma was increased by 42.9 and 38.2 %. It was found that trypsin, thrombin, and tryptase induced up to 200, 320, and 310 % increase in TNF-α release from monocytes at 16 h, respectively. PAR-1 agonist peptide, SFLLR-NH 2 , and PAR-2 agonist peptide tc-LIGRLO-NH 2 provoked up to 210 and 240 % increase in release of TNF-α. Since SCH 79797, a PAR-1 antagonist, and PD98059, an inhibitor of ERK inhibited thrombin- and SFLLR-NH 2 -induced TNF-α release, the action of thrombin is most likely through a PAR-1- and ERK-mediated signaling mechanism. Similarly, because FSLLRN-NH 2 , an inhibitor of PAR-2 diminished tryptase- and tc-LIGRLO-NH 2 -induced TNF-α release, the action of tryptase appears PAR-2 dependent. Moreover, in vivo study showed that both recombinant cockroach major allergens Per a 1 and Per a 7 provoked upregulation of PAR-2 and PAR-1 expression on CD14+ cells in OVA-sensitized mouse peritoneum. In conclusion, increased expression of PAR-2 in monocytes of AR and asthma implicates that PAR-2 likely play a role in allergy. PAR-2- and PAR-1-mediated TNF-α release from monocytes suggests that these unique protease receptors are involved in the pathogenesis of inflammation.

The role of protease-activated receptors PAR-1 and PAR-2 in the repair of 16HBE 14o(-) epithelial cell monolayers in vitro.

PubMed

Ewen, D; Clarke, S L; Smith, J R; Berger, C; Salmon, G; Trevethick, M; Shute, J K

2010-03-01

We recently reported that repair following mechanical wounding of epithelial cell layers in vitro is dependent on fibrin formation and the activity of locally expressed coagulation cascade proteins. Serine proteases of the coagulation cascade are an important group of protease-activated receptor (PAR) activators and PAR-1 to 4 are expressed by the normal bronchial epithelium. We tested the hypothesis that activation of PAR-1 and PAR-2 by coagulation cascade proteases stimulates epithelial repair via effects on fibrin formation. Using mechanically wounded 16HBE 14o(-) epithelial cell layers in culture, we investigated the effect of PAR-1 and PAR-2 agonist peptides, control partially scrambled peptides and PAR-neutralizing antibodies on the rate of repair and fibrin formation. Coagulation factors in culture supernatants were measured by immunoblot. RT-PCR was used to investigate PAR-1, PAR-2 and PGE2 receptor (EP-1 to EP-4) expression in this model and qRT-PCR to quantify responses to wounding. Additionally, we investigated the effect of exogenously added factor Xa (FXa) and neutrophil elastase and the influence of PGE2 and indomethacin on the repair response. PAR-1 and PAR-2 peptide agonists stimulated the rate of repair and enhanced the formation of a fibrin provisional matrix to support the repair process. Conversely, PAR-neutralizing antibodies inhibited repair. Under serum-free culture conditions, 16HBE 14o(-) cells expressed EP-2 and EP-3, but not EP-1 or EP-4, receptors. Wounding induced an increased expression of EP-3 but did not alter EP-2, PAR-1 or PAR-2 expression. In the absence of PAR agonists, there was no evidence for a role for PGE2 in fibrin formation or the repair process. Indomethacin attenuated fibrin formation in wounded cultures only in the presence of the PAR-2 peptide. FXa stimulated epithelial repair while neutrophil elastase reduced the levels of coagulation factors and inhibited repair. Locally expressed serine proteases of the coagulation cascade activate PAR-1 and PAR-2 to enhance fibrin formation and bronchial epithelial repair.

Cleavage of the urokinase receptor (uPAR) on oral cancer cells: regulation by transforming growth factor - β1 (TGF-β1) and potential effects on migration and invasion.

PubMed

Magnussen, Synnove Norvoll; Hadler-Olsen, Elin; Costea, Daniela Elena; Berg, Eli; Jacobsen, Cristiane Cavalcanti; Mortensen, Bente; Salo, Tuula; Martinez-Zubiaurre, Inigo; Winberg, Jan-Olof; Uhlin-Hansen, Lars; Svineng, Gunbjorg

2017-05-19

Urokinase plasminogen activator (uPA) receptor (uPAR) is up-regulated at the invasive tumour front of human oral squamous cell carcinoma (OSCC), indicating a role for uPAR in tumour progression. We previously observed elevated expression of uPAR at the tumour-stroma interface in a mouse model for OSCC, which was associated with increased proteolytic activity. The tumour microenvironment regulated uPAR expression, as well as its glycosylation and cleavage. Both full-length- and cleaved uPAR (uPAR (II-III)) are involved in highly regulated processes such as cell signalling, proliferation, migration, stem cell mobilization and invasion. The aim of the current study was to analyse tumour associated factors and their effect on uPAR cleavage, and the potential implications for cell proliferation, migration and invasion. Mouse uPAR was stably overexpressed in the mouse OSCC cell line AT84. The ratio of full-length versus cleaved uPAR as analysed by Western blotting and its regulation was assessed by addition of different protease inhibitors and transforming growth factor - β1 (TGF-β1). The role of uPAR cleavage in cell proliferation and migration was analysed using real-time cell analysis and invasion was assessed using the myoma invasion model. We found that when uPAR was overexpressed a proportion of the receptor was cleaved, thus the cells presented both full-length uPAR and uPAR (II-III). Cleavage was mainly performed by serine proteases and urokinase plasminogen activator (uPA) in particular. When the OSCC cells were stimulated with TGF-β1, the production of the uPA inhibitor PAI-1 was increased, resulting in a reduction of uPAR cleavage. By inhibiting cleavage of uPAR, cell migration was reduced, and by inhibiting uPA activity, invasion was reduced. We could also show that medium containing soluble uPAR (suPAR), and cleaved soluble uPAR (suPAR (II-III)), induced migration in OSCC cells with low endogenous levels of uPAR. These results show that soluble factors in the tumour microenvironment, such as TGF-β1, PAI-1 and uPA, can influence the ratio of full length and uPAR (II-III) and thereby potentially effect cell migration and invasion. Resolving how uPAR cleavage is controlled is therefore vital for understanding how OSCC progresses and potentially provides new targets for therapy.

Proteinase-Activated Receptor 1 (PAR1) Regulates Leukemic Stem Cell Functions

PubMed Central

Bäumer, Nicole; Krause, Annika; Köhler, Gabriele; Lettermann, Stephanie; Evers, Georg; Hascher, Antje; Bäumer, Sebastian; Berdel, Wolfgang E.

2014-01-01

External signals that are mediated by specific receptors determine stem cell fate. The thrombin receptor PAR1 plays an important role in haemostasis, thrombosis and vascular biology, but also in tumor biology and angiogenesis. Its expression and function in hematopoietic stem cells is largely unknown. Here, we analyzed expression and function of PAR1 in primary hematopoietic cells and their leukemic counterparts. AML patients' blast cells expressed much lower levels of PAR1 mRNA and protein than CD34+ progenitor cells. Constitutive Par1-deficiency in adult mice did not affect engraftment or stem cell potential of hematopoietic cells. To model an AML with Par1-deficiency, we retrovirally introduced the oncogene MLL-AF9 in wild type and Par1−/− hematopoietic progenitor cells. Par1-deficiency did not alter initial leukemia development. However, the loss of Par1 enhanced leukemic stem cell function in vitro and in vivo. Re-expression of PAR1 in Par1−/− leukemic stem cells delayed leukemogenesis in vivo. These data indicate that Par1 contributes to leukemic stem cell maintenance. PMID:24740120

Proteinase-Activated Receptor 1 (PAR1) regulates leukemic stem cell functions.

PubMed

Bäumer, Nicole; Krause, Annika; Köhler, Gabriele; Lettermann, Stephanie; Evers, Georg; Hascher, Antje; Bäumer, Sebastian; Berdel, Wolfgang E; Müller-Tidow, Carsten; Tickenbrock, Lara

2014-01-01

External signals that are mediated by specific receptors determine stem cell fate. The thrombin receptor PAR1 plays an important role in haemostasis, thrombosis and vascular biology, but also in tumor biology and angiogenesis. Its expression and function in hematopoietic stem cells is largely unknown. Here, we analyzed expression and function of PAR1 in primary hematopoietic cells and their leukemic counterparts. AML patients' blast cells expressed much lower levels of PAR1 mRNA and protein than CD34+ progenitor cells. Constitutive Par1-deficiency in adult mice did not affect engraftment or stem cell potential of hematopoietic cells. To model an AML with Par1-deficiency, we retrovirally introduced the oncogene MLL-AF9 in wild type and Par1-/- hematopoietic progenitor cells. Par1-deficiency did not alter initial leukemia development. However, the loss of Par1 enhanced leukemic stem cell function in vitro and in vivo. Re-expression of PAR1 in Par1-/- leukemic stem cells delayed leukemogenesis in vivo. These data indicate that Par1 contributes to leukemic stem cell maintenance.

Radiofrequency pulse design using nonlinear gradient magnetic fields.

PubMed

Kopanoglu, Emre; Constable, R Todd

2015-09-01

An iterative k-space trajectory and radiofrequency (RF) pulse design method is proposed for excitation using nonlinear gradient magnetic fields. The spatial encoding functions (SEFs) generated by nonlinear gradient fields are linearly dependent in Cartesian coordinates. Left uncorrected, this may lead to flip angle variations in excitation profiles. In the proposed method, SEFs (k-space samples) are selected using a matching pursuit algorithm, and the RF pulse is designed using a conjugate gradient algorithm. Three variants of the proposed approach are given: the full algorithm, a computationally cheaper version, and a third version for designing spoke-based trajectories. The method is demonstrated for various target excitation profiles using simulations and phantom experiments. The method is compared with other iterative (matching pursuit and conjugate gradient) and noniterative (coordinate-transformation and Jacobian-based) pulse design methods as well as uniform density spiral and EPI trajectories. The results show that the proposed method can increase excitation fidelity. An iterative method for designing k-space trajectories and RF pulses using nonlinear gradient fields is proposed. The method can either be used for selecting the SEFs individually to guide trajectory design, or can be adapted to design and optimize specific trajectories of interest. © 2014 Wiley Periodicals, Inc.

Loss of Par-1a/MARK3/C-TAK1 kinase leads to reduced adiposity, resistance to hepatic steatosis, and defective gluconeogenesis.

PubMed

Lennerz, Jochen K; Hurov, Jonathan B; White, Lynn S; Lewandowski, Katherine T; Prior, Julie L; Planer, G James; Gereau, Robert W; Piwnica-Worms, David; Schmidt, Robert E; Piwnica-Worms, Helen

2010-11-01

Par-1 is an evolutionarily conserved protein kinase required for polarity in worms, flies, frogs, and mammals. The mammalian Par-1 family consists of four members. Knockout studies of mice implicate Par-1b/MARK2/EMK in regulating fertility, immune homeostasis, learning, and memory as well as adiposity, insulin hypersensitivity, and glucose metabolism. Here, we report phenotypes of mice null for a second family member (Par-1a/MARK3/C-TAK1) that exhibit increased energy expenditure, reduced adiposity with unaltered glucose handling, and normal insulin sensitivity. Knockout mice were protected against high-fat diet-induced obesity and displayed attenuated weight gain, complete resistance to hepatic steatosis, and improved glucose handling with decreased insulin secretion. Overnight starvation led to complete hepatic glycogen depletion, associated hypoketotic hypoglycemia, increased hepatocellular autophagy, and increased glycogen synthase levels in Par-1a(-/-) but not in control or Par-1b(-/-) mice. The intercrossing of Par-1a(-/-) with Par-1b(-/-) mice revealed that at least one of the four alleles is necessary for embryonic survival. The severity of phenotypes followed a rank order, whereby the loss of one Par-1b allele in Par-1a(-/-) mice conveyed milder phenotypes than the loss of one Par-1a allele in Par-1b(-/-) mice. Thus, although Par-1a and Par-1b can compensate for one another during embryogenesis, their individual disruption gives rise to distinct metabolic phenotypes in adult mice.

Application of Plasma Waveguides to High Energy Accelerators

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

Milchberg, Howard M

2013-03-30

The eventual success of laser-plasma based acceleration schemes for high-energy particle physics will require the focusing and stable guiding of short intense laser pulses in reproducible plasma channels. For this goal to be realized, many scientific issues need to be addressed. These issues include an understanding of the basic physics of, and an exploration of various schemes for, plasma channel formation. In addition, the coupling of intense laser pulses to these channels and the stable propagation of pulses in the channels require study. Finally, new theoretical and computational tools need to be developed to aid in the design and analysismore » of experiments and future accelerators. Here we propose a 3-year renewal of our combined theoretical and experimental program on the applications of plasma waveguides to high-energy accelerators. During the past grant period we have made a number of significant advances in the science of laser-plasma based acceleration. We pioneered the development of clustered gases as a new highly efficient medium for plasma channel formation. Our contributions here include theoretical and experimental studies of the physics of cluster ionization, heating, explosion, and channel formation. We have demonstrated for the first time the generation of and guiding in a corrugated plasma waveguide. The fine structure demonstrated in these guides is only possible with cluster jet heating by lasers. The corrugated guide is a slow wave structure operable at arbitrarily high laser intensities, allowing direct laser acceleration, a process we have explored in detail with simulations. The development of these guides opens the possibility of direct laser acceleration, a true miniature analogue of the SLAC RF-based accelerator. Our theoretical studies during this period have also contributed to the further development of the simulation codes, Wake and QuickPIC, which can be used for both laser driven and beam driven plasma based acceleration schemes. We will continue our development of advanced simulation tools by modifying the QuickPIC algorithm to allow for the simulation of plasma particle pick-up by the wake fields. We have also performed extensive simulations of plasma slow wave structures for efficient THz generation by guided laser beams or accelerated electron beams. We will pursue experimental studies of direct laser acceleration, and THz generation by two methods, ponderomotive-induced THz polarization, and THz radiation by laser accelerated electron beams. We also plan to study both conventional and corrugated plasma channels using our new 30 TW in our new lab facilities. We will investigate production of very long hydrogen plasma waveguides (5 cm). We will study guiding at increasing power levels through the onset of laser-induced cavitation (bubble regime) to assess the role played by the preformed channel. Experiments in direct acceleration will be performed, using laser plasma wakefields as the electron injector. Finally, we will use 2-colour ionization of gases as a high frequency THz source (<60 THz) in order for femtosecond measurements of low plasma densities in waveguides and beams.« less

Testing UK blood donors for exposure to human parvovirus 4 using a time-resolved fluorescence immunoassay to screen sera and Western blot to confirm reactive samples.

PubMed

Maple, Peter A C; Beard, Stuart; Parry, Ruth P; Brown, Kevin E

2013-10-01

Human parvovirus 4 (ParV4), a newly described member of the family Parvoviridae, like B19V, has been found in pooled plasma preparations. The extent, and significance, of ParV4 exposure in UK blood donors remain to be determined and reliable detection of ParV4 immunoglobulin (Ig)G, using validated methods, is needed. With ParV4 virus-like particles a ParV4 IgG time-resolved fluorescence immunoassay (TRFIA) was developed. There is no gold standard or reference assay for measuring ParV4 IgG and the utility of the TRFIA was first examined using a panel of sera from people who inject drugs (PWIDS)--a high-prevalence population for ParV4 infection. Western blotting was used to confirm the specificity of TRFIA-reactive sera. Two cohorts of UK blood donor sera comprising 452 sera collected in 1999 and 156 sera collected in 2009 were tested for ParV4 IgG. Additional testing for B19V IgG, hepatitis C virus antibodies (anti-HCV), and ParV4 DNA was also undertaken. The rate of ParV4 IgG seroprevalence in PWIDS was 20.7% and ParV4 IgG was positively associated with the presence of anti-HCV with 68.4% ParV4 IgG-positive sera testing anti-HCV-positive versus 17.1% ParV4 IgG-negative sera. Overall seropositivity for ParV4 IgG, in 608 UK blood donors was 4.76%. The ParV4 IgG seropositivity for sera collected in 1999 was 5.08%, compared to 3.84% for sera collected in 2009. No ParV4 IgG-positive blood donor sera had detectable ParV4 DNA. ParV4 IgG has been found in UK blood donors and this finding needs further investigation. © 2013 American Association of Blood Banks.

PAR-2 regulates dental pulp inflammation associated with caries.

PubMed

Lundy, F T; About, I; Curtis, T M; McGahon, M K; Linden, G J; Irwin, C R; El Karim, I A

2010-07-01

Protease-activated receptors (PARs) are G-protein-coupled receptors that are activated enzymatically by proteolysis of an N-terminal domain. The cleavage and activation of PARs by serine proteases represent a novel mechanism by which such enzymes could influence the host inflammatory response. The aim of this study was to determine whether PAR-2 expression and activation were increased in dental caries. Using immunohistochemistry, we showed PAR-2 to be localized to pulp cells subjacent to caries lesions, but minimally expressed by healthy pulp tissue. Trypsin and the PAR-2 agonist (PAR2-AP) activated PAR-2 in an in vitro functional assay. Endogenous molecules present in pulp cell lysates from carious teeth specifically activated PAR-2, but those from healthy teeth failed to do so. The activation of PAR-2 in vitro was shown to increase the expression of the pro-inflammatory mediator cyclo-oxygenase-2 (COX-2), providing a mechanism whereby PAR-2 could modulate pulpal inflammation.

Effect and mechanism of PAR-2 on the proliferation of esophageal cancer cells.

PubMed

Quanjun, D; Qingyu, Z; Qiliang, Z; Liqun, X; Jinmei, C; Ziquan, L; Shike, H

2016-11-01

Esophageal Cancer (EC) is a common malignant tumor occurred in the digestive tract. In this study, we investigated the mechanism of Protease Activated Receptor 2 (PAR-2) on the proliferation of esophageal cancer cell. Transfected esophageal cancer (EC) cell (PAR-2shRNA EC109) was established with low stable PAR-2 expression. EC109 cell was treated with PAR-2 agonist, PAR-2 anti-agonist and MAPK inhibitor respectively; Untreated EC109 cell (blank control) and PAR-2shRNA EC109 cell were used for analysis also. The mRNA expressions of PAR-2, ERK1, Cyclin D1, and c-fos in each group were detected by reverse transcript and polymerase chain reaction. Western blot was used to detect the protein expressions in each group. The cell growth curves were drawn to compare the cell growth. Compared with the blank control, the mRNA and protein expressions of PAR-2, Cyclin D1, and c-fos in PAR-2 agonist group increased significantly (p < 0.05), while decreased significantly in PAR-2shRNA EC109 cell and MAPK inhibitor group (p < 0.05). The mRNA expression of ERK1 and protein expression of p-ERK1 increased in PAR-2 agonist group, decreased in PAR-2shRNA EC109 cell and MAPK inhibitor group when compared with blank control (p < 0.05). The growth of cells was upward in PAR-2 agonist group at cell growth phase when compared with blank control, while decreased in PAR-2 shRNA EC109 cell and MAPK inhibitor group with statistical difference (p < 0.05). PAR-2 regulate cell proliferation through the MAPK pathway in esophageal carcinoma cell, and Cyclin D1, c-fos are involved in this process.

Protease-activated Receptor-4 Signaling and Trafficking Is Regulated by the Clathrin Adaptor Protein Complex-2 Independent of β-Arrestins*

PubMed Central

Smith, Thomas H.; Coronel, Luisa J.; Li, Julia G.; Dores, Michael R.; Nieman, Marvin T.; Trejo, JoAnn

2016-01-01

Protease-activated receptor-4 (PAR4) is a G protein-coupled receptor (GPCR) for thrombin and is proteolytically activated, similar to the prototypical PAR1. Due to the irreversible activation of PAR1, receptor trafficking is intimately linked to signal regulation. However, unlike PAR1, the mechanisms that control PAR4 trafficking are not known. Here, we sought to define the mechanisms that control PAR4 trafficking and signaling. In HeLa cells depleted of clathrin by siRNA, activated PAR4 failed to internalize. Consistent with clathrin-mediated endocytosis, expression of a dynamin dominant-negative K44A mutant also blocked activated PAR4 internalization. However, unlike most GPCRs, PAR4 internalization occurred independently of β-arrestins and the receptor's C-tail domain. Rather, we discovered a highly conserved tyrosine-based motif in the third intracellular loop of PAR4 and found that the clathrin adaptor protein complex-2 (AP-2) is important for internalization. Depletion of AP-2 inhibited PAR4 internalization induced by agonist. In addition, mutation of the critical residues of the tyrosine-based motif disrupted agonist-induced PAR4 internalization. Using Dami megakaryocytic cells, we confirmed that AP-2 is required for agonist-induced internalization of endogenous PAR4. Moreover, inhibition of activated PAR4 internalization enhanced ERK1/2 signaling, whereas Akt signaling was markedly diminished. These findings indicate that activated PAR4 internalization requires AP-2 and a tyrosine-based motif and occurs independent of β-arrestins, unlike most classical GPCRs. Moreover, these findings are the first to show that internalization of activated PAR4 is linked to proper ERK1/2 and Akt activation. PMID:27402844

TGF-β induced PAR-1 expression promotes tumor progression and osteoclast differentiation in giant cell tumor of bone.

PubMed

Wang, Ting; Jiao, Jian; Zhang, Hao; Zhou, Wang; Li, Zhenxi; Han, Shuai; Wang, Jing; Yang, Xinghai; Huang, Quan; Wu, Zhipeng; Yan, Wangjun; Xiao, Jianru

2017-10-15

Although protease activated receptor-1 (PAR-1) has been confirmed as an oncogene in many cancers, the role of PAR-1 in giant cell tumor (GCT) of bone has been rarely reported. The mechanism of PAR-1 in tumor-induced osteoclastogenesis still remains unclear. In the present study, we detected that PAR-1 was significantly upregulated in GCT of bone compared to normal tissues, while TGF-β was also overexpressed in GCT tissues and could promote the expression of PAR-1 in a dose and time dependent manner. Using the luciferase reporter assay, we found that two downstreams of TGF-β, Smad3 and Smad4, could activate the promoter of PAR-1, which might explain the mechanism of TGF-β induced PAR-1 expression. Meanwhile, PAR-1 was also overexpressed in microvesicles from stromal cells of GCT (GCTSCs), and might be transported from GCTSCs to monocytes through microvesicles. In addition, knockout of PAR-1 by TALENs in GCTSCs inhibited tumor growth, angiogenesis and osteoclastogenesis in GCT in vitro. Using the chick CAM models, we further showed that inhibition of PAR-1 suppressed tumor growth and giant cell formation in vivo. Using microarray assay, we detected a number of genes involved in osteoclastogenesis as the possible downstreams of PAR-1, which may partly explain the mechanism of PAR-1 in GCT. In brief, for the first time, these results reveal an upstream regulatory role of TGF-β in PAR-1 expression, and PAR-1 expression promotes tumor growth, angiogenesis and osteoclast differentiation in GCT of bone. Hence, PAR-1 represents a novel potential therapeutic target for GCT of bone. © 2017 UICC.

Discovery of potent peptide-mimetic antagonists for the human thrombin receptor, protease-activated receptor-1 (PAR-1).

PubMed

Maryanoff, Bruce E; Zhang, Han-Cheng; Andrade-Gordon, Patricia; Derian, Claudia K

2003-03-01

Protease-activated receptors (PARs) represent a unique family of seven-transmembrane G-protein-coupled receptors, which are enzymatically cleaved to expose a new extracellular N-terminus that acts as a tethered activating ligand. PAR-1 is cleaved and activated by the serine protease alpha-thrombin, is expressed in various tissues (e.g. platelets and vascular cells), and is involved in cellular responses associated with hemostasis, proliferation, and tissue injury. By using a de novo design approach, we have discovered a series of potent heterocycle-based peptide-miimetic antagonists of PAR-1, exemplified by advanced leads RWJ-56110 (22) and RWJ-58259 (32). These compounds are potent, selective PAR-1 antagonists, devoid of PAR-1 agonist and thrombin inhibitory activity: they bind to PAR-1, interfere with calcium mobilization and cellular functions associated with PAR-1, and do not affect PAR-2, PAR-3, or PAR-4. RWJ-56110 was determined to be a direct inhibitor of PAR-1 activation and internalization, without affecting PAR-1 N-terminal cleavage. At high concentrations of alpha-thrombin, RWJ-56110 fully blocked activation responses in human vascular cells, but not in human platelets; whereas, at high concentrations of TRAP-6, RWJ-56110 blocked activation responses in both cell types. This result is consistent with the presence of another thrombin receptor on human platelets, namely PAR-4. RWJ-56110 and RWJ-58259 clearly interrupt the binding of a tethered ligand to its receptor. RWJ-58259 demonstrated antirestenotic activity in a rat balloon angioplasty model and antithrombotic activity in a cynomolgus monkey arterial injury model. Such PAR-1 antagonists should not only serve as useful tools to delineate the physiological and pathophysiological roles of PAR-1, but also may have therapeutic potential for treating thrombosis and restenosis in humans.

Elements for harnessing participatory action research to strengthen health managers' capacity: a critical interpretative synthesis.

PubMed

Tetui, Moses; Zulu, Joseph Mumba; Hurtig, Anna-Karin; Ekirapa-Kiracho, Elizabeth; Kiwanuka, Suzanne N; Coe, Anna-Britt

2018-04-19

Health managers play a key role in ensuring that health services are responsive to the needs of the population. Participatory action research (PAR) is one of the approaches that have been used to strengthen managers' capacity. However, collated knowledge on elements for harnessing PAR to strengthen managers' capacity is missing. This paper bridges this gap by reviewing existing literature on the subject matter. A critical interpretive synthesis method was used to interrogate eight selected articles. These articles reported the use of PAR to strengthen health managers' capacity. The critical interpretive synthesis method's approach to analysis guided the synthesis. Here, the authors interpretively made connections and linkages between different elements identified in the literature. Finally, the Atun et al. (Heal Pol Plann, 25:104-111, 2010) framework on integration was used to model the elements synthesised in the literature into five main domains. Five elements with intricate bi-directional interactions were identified in the literature reviewed. These included a shared purpose, skilled facilitation and psychological safety, activity integration into organisational procedures, organisational support, and external supportive monitoring. A shared purpose of the managers' capacity strengthening initiative created commitment and motivation to learn. This purpose was built upon a set of facilitation skills that included promoting participation, self-efficacy and reflection, thereby creating a safe psychological space within which the managers interacted and learnt from each other and their actions. Additionally, an integrated intervention strengthened local capacity and harnessed organisational support for learning. Finally, supportive monitoring from external partners, such as researchers, ensured quality, building of local capacity and professional safety networks essential for continued learning. The five elements identified in this synthesis provide a basis upon which the use of PAR can be harnessed, not only to strengthen health managers' capacity, but also to foster other health systems strengthening initiatives involving implementation research. In addition, the findings demonstrated the intricate and complex relations between the elements, which further affirms the need for a systems thinking approach to tackling health systems challenges.

Proteinase-activated receptors (PARs) – focus on receptor-receptor-interactions and their physiological and pathophysiological impact

PubMed Central

2013-01-01

Proteinase-activated receptors (PARs) are a subfamily of G protein-coupled receptors (GPCRs) with four members, PAR1, PAR2, PAR3 and PAR4, playing critical functions in hemostasis, thrombosis, embryonic development, wound healing, inflammation and cancer progression. PARs are characterized by a unique activation mechanism involving receptor cleavage by different proteinases at specific sites within the extracellular amino-terminus and the exposure of amino-terminal “tethered ligand“ domains that bind to and activate the cleaved receptors. After activation, the PAR family members are able to stimulate complex intracellular signalling networks via classical G protein-mediated pathways and beta-arrestin signalling. In addition, different receptor crosstalk mechanisms critically contribute to a high diversity of PAR signal transduction and receptor-trafficking processes that result in multiple physiological effects. In this review, we summarize current information about PAR-initiated physical and functional receptor interactions and their physiological and pathological roles. We focus especially on PAR homo- and heterodimerization, transactivation of receptor tyrosine kinases (RTKs) and receptor serine/threonine kinases (RSTKs), communication with other GPCRs, toll-like receptors and NOD-like receptors, ion channel receptors, and on PAR association with cargo receptors. In addition, we discuss the suitability of these receptor interaction mechanisms as targets for modulating PAR signalling in disease. PMID:24215724

The 14-3-3 Protein PAR-5 Regulates the Asymmetric localization of the LET-99 Spindle Positioning Protein

PubMed Central

Rose, Lesilee S.

2016-01-01

PAR proteins play important roles in establishing cytoplasmic polarity as well as regulating spindle positioning during asymmetric division. However, the molecular mechanisms by which the PAR proteins generate asymmetry in different cell types are still being elucidated. Previous studies in C. elegans revealed that PAR-3 and PAR-1 regulate the asymmetric localization of LET-99, which in turn controls spindle positioning by affecting the distribution of the conserved force generating complex. In wild-type embryos, LET-99 is localized in a lateral cortical band pattern, via inhibition at the anterior by PAR-3 and at the posterior by PAR-1. In this report, we show that the 14-3-3 protein PAR-5 is also required for cortical LET-99 asymmetry. PAR-5 associated with LET-99 in pull-down assays, and two PAR-5 binding sites were identified in LET-99 using the yeast two-hybrid assay. Mutation of these sites abolished binding in yeast and altered LET-99 localization in vivo: LET-99 was present at the highest levels at the posterior pole of the embryo instead of a band in par-5 embryos. Together the results indicate that PAR-5 acts in a mechanism with PAR-1 to regulate LET-99 cortical localization. PMID:26921457

Telemetry with an Optical Fiber Revisited: An Alternative Strategy

ERIC Educational Resources Information Center

Kraftmakher, Yaakov

2014-01-01

With a new data-acquisition system developed by PASCO scientific, an experiment on telemetry with an optical fiber can be made easier and more accurate. For this aim, an alternative strategy of the remote temperature measurements is proposed: the frequency of light pulses transmitted via the light guide numerically equals the temperature using…

System for testing optical fibers

DOEpatents

Davies, Terence J.; Franks, Larry A.; Nelson, Melvin A.

1981-01-01

A system for nondestructively determining the attenuation coefficient, .alpha.(.lambda.), of low-loss optical fiber wave guides. Cerenkov light pulses are generated at a plurality of locations in the fiber by a beam of charged particles. The transit times of selected spectral components and their intensities are utilized to unfold the .alpha.(.lambda.) values over the measured spectrum.

Emissive color preferences and temporal alteration of walking performance by pulsing lights in colorado potato beetle

USDA-ARS?s Scientific Manuscript database

The Colorado potato beetle (CPB) Leptinotarsa decemlineata (Say 1824) is a diurnal insect that strongly relies on vision to guide its walk. In the present study, we investigated the orientation behavior of nondiapausing walking CPB in response to emissive colors produced by light emitting diodes (L...

Quantitative Diagnostics of Multilayered Composite Structures with Ultrasonic Guided Waves

DTIC Science & Technology

2014-09-01

sensors. These IDT sensors were fabricated from thin wafer of piezoelectric lead zirconate titanate ( PZT ) substrates by using a pulse laser micro...pavement structures," J. Acoust. Soc. Am., vol. 116, no. 5, pp. 2902-2913, 2004. [9] E. Kostson and P. Fromme, " Fatigue crack growth monitoring in multi

Genotypic characterization of quinolone resistant-Escherichia coli isolates from retail food in Morocco.

PubMed

Nayme, Kaotar; Barguigua, Abouddihaj; Bouchrif, Brahim; Karraouan, Bouchra; El Otmani, Fatima; Elmdaghri, Naima; Zerouali, Khalid; Timinouni, Mohammed

2017-02-01

This study was conducted to assess the retail food as a possible vehicle for antimicrobial resistant, particularly quinolones resistant and pathogenic Escherichia coli. We determined the prevalence and characteristics of nalidixic acid (Nal) resistant E. coli isolates from diverse retail food samples. In all, 70 (28%) of 250 E. coli isolates studied were Nal-resistant E. coli and 91% of these were multi-drug resistant. Plasmid mediated quinolone resistance genes were identified in 32 isolates, including aac(6')-Ib-cr (n = 16), qnrS1 (n = 11) and qnrB19 (n = 7). Mutations in gyr A and par C genes were detected among 80% of the isolates, and the isolates showed substitution Ser83-Leu and Asp87-Asn in gyrA and Ser80-Ile in parC. In addition, three different gene cassettes were identified (aadA1, aadA7, aac(3)-Id) in 18%. Virulence-associated genes stx1, eae, sfa, hlyA and stx2 were found in six (8%), three (4%), two (3%), three (4%) and three (4%) isolates, respectively. E. coli isolates of phylogenetic group A were dominant (64%, 45/70). Pulsed field gel electrophoresis revealed none epidemiological relationship between these isolates. The results of this work report the higher frequency of Nal-resistant E. coli isolates from Moroccan retail food samples including MDR and pathogenic isolates.

Highly coherent mid-IR supercontinuum by self-defocusing solitons in lithium niobate waveguides with all-normal dispersion.

PubMed

Guo, Hairun; Zhou, Binbin; Zeng, Xianglong; Bache, Morten

2014-05-19

We numerically investigate self-defocusing solitons in a lithium niobate (LN) waveguide designed to have a large refractive index (RI) change. The waveguide evokes strong waveguide dispersion and all-normal dispersion is found in the entire guiding band spanning the near-IR and the beginning of the mid-IR. Meanwhile, a self-defocusing nonlinearity is invoked by the cascaded (phase-mismatched) second-harmonic generation under a quasi-phase-matching pitch. Combining this with the all-normal dispersion, mid-IR solitons can form and the waveguide presents the first all-nonlinear and solitonic device where no linear dispersion (i.e. non-solitonic) regimes exist within the guiding band. Soliton compressions at 2 μm and 3 μm are investigated, with nano-joule single cycle pulse formations and highly coherent octave-spanning supercontinuum generations. With an alternative design on the waveguide dispersion, the soliton spectral tunneling effect is also investigated, with which few-cycle pico-joule pulses at 2 μm are formed by a near-IR pump.

TH-F-202-03: Advances in MRI for Radiation Therapy

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

Cai, J.

MRI has excellent soft tissue contrast and can provide both anatomical and physiological information. It is becoming increasingly important in radiation therapy for treatment planning, image-guided radiation therapy, and treatment assessment. It is critically important at this time point to educate and update our medical physicists about MRI to prepare for the upcoming surge of MRI applications in radiation therapy. This session will review important basics of MR physics, pulse sequence designs, and current radiotherapy application, as well as showcase exciting new developments in MRI that can be potentially useful in radiation therapy. Learning Objectives: To learn basics of MRmore » physics and understand the differences between various pulse sequences To review current applications of MRI in radiation therapy.To discuss recent MRI advances for future MRI guided radiation therapy Partly supported by NIH (1R21CA165384).; W. Miller, Research supported in part by Siemens Healthcare; G. Li, My clinical research is in part supported by NIH U54CA137788. I have a collaborative research project with Philips Healthcare.; J. Cai, jing cai.« less

TH-F-202-00: MRI for Radiation Therapy

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

NONE

MRI has excellent soft tissue contrast and can provide both anatomical and physiological information. It is becoming increasingly important in radiation therapy for treatment planning, image-guided radiation therapy, and treatment assessment. It is critically important at this time point to educate and update our medical physicists about MRI to prepare for the upcoming surge of MRI applications in radiation therapy. This session will review important basics of MR physics, pulse sequence designs, and current radiotherapy application, as well as showcase exciting new developments in MRI that can be potentially useful in radiation therapy. Learning Objectives: To learn basics of MRmore » physics and understand the differences between various pulse sequences To review current applications of MRI in radiation therapy.To discuss recent MRI advances for future MRI guided radiation therapy Partly supported by NIH (1R21CA165384).; W. Miller, Research supported in part by Siemens Healthcare; G. Li, My clinical research is in part supported by NIH U54CA137788. I have a collaborative research project with Philips Healthcare.; J. Cai, jing cai.« less

TH-F-202-01: MRI Basics

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

Miller, W.

MRI has excellent soft tissue contrast and can provide both anatomical and physiological information. It is becoming increasingly important in radiation therapy for treatment planning, image-guided radiation therapy, and treatment assessment. It is critically important at this time point to educate and update our medical physicists about MRI to prepare for the upcoming surge of MRI applications in radiation therapy. This session will review important basics of MR physics, pulse sequence designs, and current radiotherapy application, as well as showcase exciting new developments in MRI that can be potentially useful in radiation therapy. Learning Objectives: To learn basics of MRmore » physics and understand the differences between various pulse sequences To review current applications of MRI in radiation therapy.To discuss recent MRI advances for future MRI guided radiation therapy Partly supported by NIH (1R21CA165384).; W. Miller, Research supported in part by Siemens Healthcare; G. Li, My clinical research is in part supported by NIH U54CA137788. I have a collaborative research project with Philips Healthcare.; J. Cai, jing cai.« less

TH-F-202-02: Current Applications of MRI in Radiotherapy

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

Li, G.

MRI has excellent soft tissue contrast and can provide both anatomical and physiological information. It is becoming increasingly important in radiation therapy for treatment planning, image-guided radiation therapy, and treatment assessment. It is critically important at this time point to educate and update our medical physicists about MRI to prepare for the upcoming surge of MRI applications in radiation therapy. This session will review important basics of MR physics, pulse sequence designs, and current radiotherapy application, as well as showcase exciting new developments in MRI that can be potentially useful in radiation therapy. Learning Objectives: To learn basics of MRmore » physics and understand the differences between various pulse sequences To review current applications of MRI in radiation therapy.To discuss recent MRI advances for future MRI guided radiation therapy Partly supported by NIH (1R21CA165384).; W. Miller, Research supported in part by Siemens Healthcare; G. Li, My clinical research is in part supported by NIH U54CA137788. I have a collaborative research project with Philips Healthcare.; J. Cai, jing cai.« less

Characteristics of Quinolone Resistance in Escherichia coli Isolates from Humans, Animals, and the Environment in the Czech Republic

PubMed Central

Röderova, Magdalena; Halova, Dana; Papousek, Ivo; Dolejska, Monika; Masarikova, Martina; Hanulik, Vojtech; Pudova, Vendula; Broz, Petr; Htoutou-Sedlakova, Miroslava; Sauer, Pavel; Bardon, Jan; Cizek, Alois; Kolar, Milan; Literak, Ivan

2017-01-01

Escherichia coli is a common commensal bacterial species of humans and animals that may become a troublesome pathogen causing serious diseases. The aim of this study was to characterize the quinolone resistance phenotypes and genotypes in E. coli isolates of different origin from one area of the Czech Republic. E. coli isolates were obtained from hospitalized patients and outpatients, chicken farms, retailed turkeys, rooks wintering in the area, and wastewaters. Susceptibility of the isolates grown on the MacConkey agar with ciprofloxacin (0.05 mg/L) to 23 antimicrobial agents was determined. The presence of plasmid-mediated quinolone resistance (PMQR) and ESBL genes was tested by PCR and sequencing. Specific mutations in gyrA, gyrB, parC, and parE were also examined. Multilocus sequence typing and pulsed-field gel electrophoresis were performed to assess the clonal relationship. In total, 1050 E. coli isolates were obtained, including 303 isolates from humans, 156 from chickens, 105 from turkeys, 114 from the rooks, and 372 from wastewater samples. PMQR genes were detected in 262 (25%) isolates. The highest occurrence was observed in isolates from retailed turkey (49% of the isolates were positive) and inpatients (32%). The qnrS1 gene was the most common PMQR determinant identified in 146 (56%) followed by aac(6′)-Ib-cr in 77 (29%), qnrB19 in 41 (16%), and qnrB1 in 9 (3%) isolates. All isolates with high level of ciprofloxacin resistance (>32 mg/L) carried double or triple mutations in gyrA combined with single or double mutations in parC. The most frequently identified substitutions were Ser(83)Leu; Asp(87)Asn in GyrA, together with Ser(80)Ile, or Glu(84)Val in ParC. Majority of these isolates showed resistance to beta-lactams and multiresistance phenotype was found in 95% isolates. Forty-eight different sequence types among 144 isolates analyzed were found, including five major clones ST131 (26), ST355 (19), ST48 (13), ST95 (10), and ST10 (5). No isolates sharing 100% relatedness and originating from different areas were identified. In conclusion, our study identified PMQR genes in E. coli isolates in all areas studied, including highly virulent multiresistant clones such as ST131 producing CTX-M-15 beta-lactamases. PMID:28119674

Observation and estimation of photosynthetically active radiation in Lhasa (Tibetan Plateau)

NASA Astrophysics Data System (ADS)

Peng, Simao; Du, Qingyun; Lin, Aiwen; Hu, Bo; Xiao, Ke; Xi, Yuliang

2015-03-01

In this study, we measured photosynthetically active radiation (PAR) and global solar radiation (G) in Lhasa, located on the Tibetan Plateau, from 2006 to 2012 to examine the PAR and PAR/G (PAR fraction) seasonal characteristics. The maximum and minimum values of both PAR and the PAR fraction occurred in summer and winter, respectively. Moreover, the PAR and PAR fraction annual averages were 38.64 mol m-2 d-1 and 1.84 mol M J-1, respectively. An efficient all-weather model used for estimating PAR under various sky conditions was developed based on the relationships among PAR, the cosine of the solar zenith angle and the clearness index in Lhasa. The model also produced acceptable estimations of PAR with high accuracy at the Donghu and Sanjiang weather stations. A PAR dataset was reconstructed from G using the newly developed model for the period 1961-2012. The modelled annual mean daily PAR was approximately 37.62 mol m-2 d-1. A significant decreasing trend (-0.61 mol m-2 per decade) over the last 50 years was observed on the Tibetan Plateau; this decrease was largest in autumn (-1.024 mol m-2 per decade), and relatively small decreases were observed in summer. The results also revealed that PAR began increasing at 0.164 mol m-2 per year from 1991 to 2012, which was inconsistent with the variations of G. The proposed all-weather PAR model could be useful for ecological modelling and agricultural processes in the Tibetan Plateau region of China.

Loss of Par-1a/MARK3/C-TAK1 Kinase Leads to Reduced Adiposity, Resistance to Hepatic Steatosis, and Defective Gluconeogenesis ▿

PubMed Central

Lennerz, Jochen K.; Hurov, Jonathan B.; White, Lynn S.; Lewandowski, Katherine T.; Prior, Julie L.; Planer, G. James; Gereau, Robert W.; Piwnica-Worms, David; Schmidt, Robert E.; Piwnica-Worms, Helen

2010-01-01

Par-1 is an evolutionarily conserved protein kinase required for polarity in worms, flies, frogs, and mammals. The mammalian Par-1 family consists of four members. Knockout studies of mice implicate Par-1b/MARK2/EMK in regulating fertility, immune homeostasis, learning, and memory as well as adiposity, insulin hypersensitivity, and glucose metabolism. Here, we report phenotypes of mice null for a second family member (Par-1a/MARK3/C-TAK1) that exhibit increased energy expenditure, reduced adiposity with unaltered glucose handling, and normal insulin sensitivity. Knockout mice were protected against high-fat diet-induced obesity and displayed attenuated weight gain, complete resistance to hepatic steatosis, and improved glucose handling with decreased insulin secretion. Overnight starvation led to complete hepatic glycogen depletion, associated hypoketotic hypoglycemia, increased hepatocellular autophagy, and increased glycogen synthase levels in Par-1a−/− but not in control or Par-1b−/− mice. The intercrossing of Par-1a−/− with Par-1b−/− mice revealed that at least one of the four alleles is necessary for embryonic survival. The severity of phenotypes followed a rank order, whereby the loss of one Par-1b allele in Par-1a−/− mice conveyed milder phenotypes than the loss of one Par-1a allele in Par-1b−/− mice. Thus, although Par-1a and Par-1b can compensate for one another during embryogenesis, their individual disruption gives rise to distinct metabolic phenotypes in adult mice. PMID:20733003

Architecture of the ParF*ParG protein complex involved in prokaryotic DNA segregation.

PubMed

Barillà, Daniela; Hayes, Finbarr

2003-07-01

The mechanism by which low copy number plasmids are segregated at cell division involves the concerted action of two plasmid-encoded proteins that assemble on a centromere-like site. This study explores the topology of the DNA segregation machinery specified by the parFG locus of TP228, a partition system which is phylogenetically distinct from more well-characterized archetypes. A variety of genetic, biochemical and biophysical strategies revealed that the ParG protein is dimeric. ParF, which is more closely related to the cell division regulator MinD than to the prototypical ParA partition protein of plasmid P1, is instead multimeric and its polymeric state appears to be modulated by ATP which correlates with the proposed ATP-binding activity of ParF. ParG interacts in a sequence-specific manner with the DNA region upstream of the parFG locus and this binding is modulated by ParF. Intriguingly, the ParF and ParG proteins form at least two types of discrete complex in the absence of this region suggesting that the assembly dynamics of these proteins onto DNA is intricate.

PAR-2 triggers placenta-derived protease-induced altered VE-cadherin reorganization at endothelial junctions in preeclampsia.

PubMed

Gu, Y; Groome, L J; Alexander, J S; Wang, Y

2012-10-01

PAR-2 is a G-protein coupled protease receptor whose activation in endothelial cells (ECs) is associated with increased solute permeability. VE-cadherin is an endothelial-specific junction protein, which exhibits a disorganized distribution at cell junction during inflammation and is a useful indicator of endothelial barrier dysfunction. In the present study, we tested the hypothesis that PAR-2 activation mediates placenta-derived chymotrypsin-like protease (CLP)-induced endothelial junction disturbance and permeability in preeclampsia (PE). PAR-2 and VE-cadherin were examined by immunofluorescent staining. Specific CLP induced PAR-2 activation and altered VE-cadherin distribution was assessed following depletion of protease chymotrypsin in the placental conditioned medium and after PAR-2 siRNA. VE-cadherin assembly was determined by treating cells with protease chymotrypsin and/or the specific PAR-2 agonist SLIGKV-NH2. Our results showed: 1) placental conditioned medium not only disturbed VE-cadherin distribution at cell junctions but also activated PAR-2 in ECs; 2) PAR-2 siRNA blocked the placental conditioned medium induced PAR-2 upregulation and disorganization of VE-cadherin at cell junctions; 3) PAR-2 agonist induced PAR-2 activation and VE-cadherin reorganization were dose-dependent; and 4) PAR-2 agonist could stimulate ERK1/2 activation. These results strongly suggest that proteases produced by the placenta elicit endothelial barrier dysfunction via a PAR-2 signaling regulatory mechanism in PE. Copyright © 2012 Elsevier Ltd. All rights reserved.

Protease Activated Receptor-2 Mediates Activated Protein C–Induced Cutaneous Wound Healing via Inhibition of p38

PubMed Central

Julovi, Sohel M.; Xue, Meilang; Dervish, Suat; Sambrook, Philip N.; March, Lyn; Jackson, Christopher John

2011-01-01

Activated protein C (APC) is a natural anticoagulant that exerts anti-inflammatory and cytoprotective properties mediated through the protease activated receptor (PAR)-1. APC can also proteolytically cleave PAR-2, although subsequent function is unknown. On the basis of recent evidence that APC promotes wound healing, the aim of this study was to determine whether APC acts through PARs to heal murine excisional wounds or to regulate human cultured keratinocyte function and to determine the signaling mechanisms. Topical administration of APC accelerated wound healing in wild-type mice and, unexpectedly, in PAR-1 knockout mice. PAR-2 knockout mice healed significantly slower than wild-type mice, and healing was not altered by adding APC, indicating that APC acts through PAR-2 to heal wounds. In cultured human primary keratinocytes, APC enhanced PAR-2, stimulated proliferation, activated phosphatidylinositol 3-kinase/Src/Akt, and inhibited phosphorylated (P)-p38. Inhibiting PAR-1 or PAR-2, by small-interfering RNA or blocking antibody, reversed APC-induced keratinocyte proliferation and Akt activation. Blocking PAR-2, but not PAR-1, reversed the inhibition of P-p38 by APC. Furthermore, inhibition of P-p38 accelerated wound healing in wild-type mice. In summary, although APC acts through both PAR-1 and PAR-2 to activate Akt and to increase keratinocyte proliferation, APC-induced murine wound healing depends on PAR-2 activity and inhibition of P-p38. PMID:21907694

PAR-2 triggers placenta-derived protease-induced altered VE-cadherin reorganization at endothelial junctions in preeclampsia

PubMed Central

Gu, Yang; Groome, Lynn J.; Alexander, J. Steven; Wang, Yuping

2014-01-01

PAR-2 is a G-protein coupled protease receptor whose activation in endothelial cells (ECs) is associated with increased solute permeability. VE-cadherin is an endothelial specific junction protein, which exhibits a disorganized distribution at cell junction during inflammation and is a useful indicator of endothelial barrier dysfunction. In the present study, we tested the hypothesis that PAR-2 activation mediates placenta-derived chymotrypsin-like protease (CLP)-induced endothelial junction disturbance and permeability in preeclampsia (PE). PAR-2 and VE-cadherin were examined by immunofluorescent staining. Specific CLP-induced PAR-2 activation and altered VE-cadherin distribution was assessed following depletion of protease chymotrypsin in the placental conditioned medium and after PAR-2 siRNA. VE-cadherin assembly was determined by treating cells with protease chymotrypsin and/or the specific PAR-2 agonist SLIGKV-NH2. Our results showed: 1) placental conditioned medium not only disturbed VE-cadherin distribution at cell junctions but also activated PAR-2 in ECs; 2) PAR-2 siRNA blocked the placental conditioned medium induced PAR-2 upregulation and disorganization of VE-cadherin at cell junctions; 3) PAR-2 agonist induced PAR-2 activation and VE-cadherin reorganization were dose-dependent; and 4) PAR-2 agonist could stimulate ERK1/2 activation. These results strongly suggest that proteases produced by the placenta elicit endothelial barrier dysfunction via a PAR-2 signaling regulatory mechanism in PE. PMID:22840244

An ELISA method detecting the active form of suPAR.

PubMed

Zhou, Xiaolei; Xu, Mingming; Huang, Hailong; Mazar, Andrew; Iqbal, Zafar; Yuan, Cai; Huang, Mingdong

2016-11-01

Urokinase plasminogen activator receptor (uPAR) exists in a number of formats in human plasma, including soluble uPAR (suPAR) and uPAR fragments. We developed an ELISA method to detect specifically the active form suPAR, which binds to its natural ligand uPA. The intra CV and inter CV of this ELISA assay is 8.5% and 9.6% respectively, and the assay can recover 99.74% of added recombinant suPAR from 10% plasma. This assay is quite sensitive, capable of detecting down to 15pg/ml of suPAR, and can measure suPAR concentrations in the range of 0.031-8ng/ml with high linear relationship. Plasma samples from pregnant women were also measured for the active form of suPAR with this assay, giving an averaged level of 1.39ng/ml, slightly higher than the level of pooled plasma from healthy donors (0.96ng/ml). This study demonstrates the feasibility to measure the active form of suPAR, which will likely have value in clinical applications. Copyright © 2016. Published by Elsevier B.V.

GigaGauss solenoidal magnetic field inside bubbles excited in under-dense plasma

PubMed Central

Lécz, Zs.; Konoplev, I. V.; Seryi, A.; Andreev, A.

2016-01-01

This paper proposes a novel and effective method for generating GigaGauss level, solenoidal quasi-static magnetic fields in under-dense plasma using screw-shaped high intensity laser pulses. This method produces large solenoidal fields that move with the driving laser pulse and are collinear with the accelerated electrons. This is in contrast with already known techniques which rely on interactions with over-dense or solid targets and generates radial or toroidal magnetic field localized at the stationary target. The solenoidal field is quasi-stationary in the reference frame of the laser pulse and can be used for guiding electron beams. It can also provide synchrotron radiation beam emittance cooling for laser-plasma accelerated electron and positron beams, opening up novel opportunities for designs of the light sources, free electron lasers, and high energy colliders based on laser plasma acceleration. PMID:27796327

GigaGauss solenoidal magnetic field inside bubbles excited in under-dense plasma

NASA Astrophysics Data System (ADS)

Lécz, Zs.; Konoplev, I. V.; Seryi, A.; Andreev, A.

2016-10-01

This paper proposes a novel and effective method for generating GigaGauss level, solenoidal quasi-static magnetic fields in under-dense plasma using screw-shaped high intensity laser pulses. This method produces large solenoidal fields that move with the driving laser pulse and are collinear with the accelerated electrons. This is in contrast with already known techniques which rely on interactions with over-dense or solid targets and generates radial or toroidal magnetic field localized at the stationary target. The solenoidal field is quasi-stationary in the reference frame of the laser pulse and can be used for guiding electron beams. It can also provide synchrotron radiation beam emittance cooling for laser-plasma accelerated electron and positron beams, opening up novel opportunities for designs of the light sources, free electron lasers, and high energy colliders based on laser plasma acceleration.

Orthogonal on-off control of radar pulses for the suppression of mutual interference

NASA Astrophysics Data System (ADS)

Kim, Yong Cheol

1998-10-01

Intelligent vehicles of the future will be guided by radars and other sensors to avoid obstacles. When multiple vehicles move simultaneously in autonomous navigational mode, mutual interference among car radars becomes a serious problem. An obstacle is illuminated with electromagnetic pulses from several radars. The signal at a radar receiver is actually a mixture of the self-reflection and the reflection of interfering pulses emitted by others. When standardized pulse- type radars are employed on vehicles for obstacle avoidance and so self-pulse and interfering pulses have identical pulse repetition interval, this SI (synchronous Interference) is very difficult to separate from the true reflection. We present a method of suppressing such a synchronous interference. By controlling the pulse emission of a radar in a binary orthogonal ON, OFF pattern, the true self-reflection can be separated from the false one. Two range maps are generated, TRM (true-reflection map) and SIM (synchronous- interference map). TRM is updated for every ON interval and SIM is updated for every OFF interval of the self-radar. SIM represents the SI of interfering radars while TRM keeps a record of a mixture of the true self-reflection and SI. Hence the true obstacles can be identified by the set subtraction operation. The performance of the proposed method is compared with that of the conventional M of N method. Bayesian analysis shows that the probability of false alarm is improved by order of 103 to approximately 106 while the deterioration in the probability of detection is negligible.

The 14-3-3 protein PAR-5 regulates the asymmetric localization of the LET-99 spindle positioning protein.

PubMed

Wu, Jui-Ching; Espiritu, Eugenel B; Rose, Lesilee S

2016-04-15

PAR proteins play important roles in establishing cytoplasmic polarity as well as regulating spindle positioning during asymmetric division. However, the molecular mechanisms by which the PAR proteins generate asymmetry in different cell types are still being elucidated. Previous studies in Caenorhabditis elegans revealed that PAR-3 and PAR-1 regulate the asymmetric localization of LET-99, which in turn controls spindle positioning by affecting the distribution of the conserved force generating complex. In wild-type embryos, LET-99 is localized in a lateral cortical band pattern, via inhibition at the anterior by PAR-3 and at the posterior by PAR-1. In this report, we show that the 14-3-3 protein PAR-5 is also required for cortical LET-99 asymmetry. PAR-5 associated with LET-99 in pull-down assays, and two PAR-5 binding sites were identified in LET-99 using the yeast two-hybrid assay. Mutation of these sites abolished binding in yeast and altered LET-99 localization in vivo: LET-99 was present at the highest levels at the posterior pole of the embryo instead of a band in par-5 embryos. Together the results indicate that PAR-5 acts in a mechanism with PAR-1 to regulate LET-99 cortical localization. Copyright © 2016 Elsevier Inc. All rights reserved.

A novel fiber laser development for photoacoustic microscopy

NASA Astrophysics Data System (ADS)

Yavas, Seydi; Aytac-Kipergil, Esra; Arabul, Mustafa U.; Erkol, Hakan; Akcaalan, Onder; Eldeniz, Y. Burak; Ilday, F. Omer; Unlu, Mehmet B.

2013-03-01

Photoacoustic microscopy, as an imaging modality, has shown promising results in imaging angiogenesis and cutaneous malignancies like melanoma, revealing systemic diseases including diabetes, hypertension, tracing drug efficiency and assessment of therapy, monitoring healing processes such as wound cicatrization, brain imaging and mapping. Clinically, photoacoustic microscopy is emerging as a capable diagnostic tool. Parameters of lasers used in photoacoustic microscopy, particularly, pulse duration, energy, pulse repetition frequency, and pulse-to-pulse stability affect signal amplitude and quality, data acquisition speed and indirectly, spatial resolution. Lasers used in photoacoustic microscopy are typically Q-switched lasers, low-power laser diodes, and recently, fiber lasers. Significantly, the key parameters cannot be adjusted independently of each other, whereas microvasculature and cellular imaging, e.g., have different requirements. Here, we report an integrated fiber laser system producing nanosecond pulses, covering the spectrum from 600 nm to 1100 nm, developed specifically for photoacoustic excitation. The system comprises of Yb-doped fiber oscillator and amplifier, an acousto-optic modulator and a photonic-crystal fiber to generate supercontinuum. Complete control over the pulse train, including generation of non-uniform pulse trains, is achieved via the AOM through custom-developed field-programmable gate-array electronics. The system is unique in that all the important parameters are adjustable: pulse duration in the range of 1-3 ns, pulse energy up to 10 μJ, repetition rate from 50 kHz to 3 MHz. Different photocoustic imaging probes can be excited with the ultrabroad spectrum. The entire system is fiber-integrated; guided-beam-propagation rendersit misalignment free and largely immune to mechanical perturbations. The laser is robust, low-cost and built using readily available components.

Laser positioning of four-quadrant detector based on pseudo-random sequence

NASA Astrophysics Data System (ADS)

Tang, Yanqin; Cao, Ercong; Hu, Xiaobo; Gu, Guohua; Qian, Weixian

2016-10-01

Nowadays the technology of laser positioning based on four-quadrant detector has the wide scope of the study and application areas. The main principle of laser positioning is that by capturing the projection of the laser spot on the photosensitive surface of the detector, and then calculating the output signal from the detector to obtain the coordinates of the spot on the photosensitive surface of the detector, the coordinate information of the laser spot in the space with respect to detector system which reflects the spatial position of the target object is calculated effectively. Given the extensive application of FPGA technology and the pseudo-random sequence has the similar correlation of white noise, the measurement process of the interference, noise has little effect on the correlation peak. In order to improve anti-jamming capability of the guided missile in tracking process, when the laser pulse emission, the laser pulse period is pseudo-random encoded which maintains in the range of 40ms-65ms so that people of interfering can't find the exact real laser pulse. Also, because the receiver knows the way to solve the pseudo-random code, when the receiver receives two consecutive laser pulses, the laser pulse period can be decoded successfully. In the FPGA hardware implementation process, around each laser pulse arrival time, the receiver can open a wave door to get location information contained the true signal. Taking into account the first two consecutive pulses received have been disturbed, so after receiving the first laser pulse, it receives all the laser pulse in the next 40ms-65ms to obtain the corresponding pseudo-random code.

Tissue Factor-Factor VIIa Complex Triggers Protease Activated Receptor 2-Dependent Growth Factor Release and Migration in Ovarian Cancer

PubMed Central

Chanakira, Alice; Westmark, Pamela R.; Ong, Irene M.; Sheehan, John P.

2017-01-01

Objective Enhanced tissue factor (TF) expression in epithelial ovarian cancer (EOC) is associated with aggressive disease. Our objective was to evaluate the role of the TF-factor VIIa-protease-activated receptor-2 (PAR-2) pathway in human EOC. Methods TCGA RNAseq data from EOC databases were analyzed for PAR expression. Cell and microparticle (MP) associated TF protein expression (Western blot) and MP-associated coagulant activity were determined in human EOC (SKOV-3, OVCAR-3 and CaOV-3) and control cell lines. PAR-1 and PAR-2 protein expression were similarly examined. The PAR dependence of VEGF-A release (ELISA) and chemotactic migration in response to FVIIa and cellular proliferation in response to thrombin was evaluated with small molecule antagonists. Results Relative mRNA expression consistently demonstrated PAR-2>PAR-1≫PAR-3/4 in multiple EOC datasets. Human EOC cell line lysates confirmed expression of TF, PAR-1 and PAR-2 proteins. MPs isolated from EOC cell lines demonstrated markedly enhanced (4–10 fold) TF coagulant activity relative to control cell lines. FVIIa induced a dose-dependent increase in VEGF-A release (2.5-3 fold) from EOC cell lines that was abrogated by the PAR-2 antagonist ENMD-1068. FVIIa treatment of CaOV-3 and OVCAR-3 cells resulted in increased chemotactic migration that was abolished by ENMD-1068. Thrombin induced dose-dependent EOC cell line proliferation was completely reversed by the PAR-1 antagonist vorapaxar. Small molecule antagonists had no effect on these phenotypes without protease present. Conclusions Enhanced activity of the TF-FVIIa-PAR-2 axis may contribute to the EOC progression via PAR-2 dependent signaling that supports an angiogenic and invasive phenotype and local thrombin generation supporting PAR-1 dependent proliferation. PMID:28148395

Proteinase-activated receptor 2 modulates OA-related pain, cartilage and bone pathology

PubMed Central

Huesa, Carmen; Ortiz, Ana C; Dunning, Lynette; McGavin, Laura; Bennett, Louise; McIntosh, Kathryn; Crilly, Anne; Kurowska-Stolarska, Mariola; Plevin, Robin; van ‘t Hof, Rob J; Rowan, Andrew D; McInnes, Iain B; Goodyear, Carl S; Lockhart, John C; Ferrell, William R

2016-01-01

Objective Proteinase-activated receptor 2 (PAR2) deficiency protects against cartilage degradation in experimental osteoarthritis (OA). The wider impact of this pathway upon OA-associated pathologies such as osteophyte formation and pain is unknown. Herein, we investigated early temporal bone and cartilage changes in experimental OA in order to further elucidate the role of PAR2 in OA pathogenesis. Methods OA was induced in wild-type (WT) and PAR2-deficient (PAR2−/−) mice by destabilisation of the medial meniscus (DMM). Inflammation, cartilage degradation and bone changes were monitored using histology and microCT. In gene rescue experiments, PAR2−/− mice were intra-articularly injected with human PAR2 (hPAR2)-expressing adenovirus. Dynamic weight bearing was used as a surrogate of OA-related pain. Results Osteophytes formed within 7 days post-DMM in WT mice but osteosclerosis was only evident from 14 days post induction. Importantly, PAR2 was expressed in the proliferative/hypertrophic chondrocytes present within osteophytes. In PAR2−/− mice, osteophytes developed significantly less frequently but, when present, were smaller and of greater density; no osteosclerosis was observed in these mice up to day 28. The pattern of weight bearing was altered in PAR2−/− mice, suggesting reduced pain perception. The expression of hPAR2 in PAR2−/− mice recapitulated osteophyte formation and cartilage damage similar to that observed in WT mice. However, osteosclerosis was absent, consistent with lack of hPAR2 expression in subchondral bone. Conclusions This study clearly demonstrates PAR2 plays a critical role, via chondrocytes, in osteophyte development and subchondral bone changes, which occur prior to PAR2-mediated cartilage damage. The latter likely occurs independently of OA-related bone changes. PMID:26698846

Protease-Activated Receptor 4 Variant p.Tyr157Cys Reduces Platelet Functional Responses and Alters Receptor Trafficking.

PubMed

Norman, Jane E; Cunningham, Margaret R; Jones, Matthew L; Walker, Mary E; Westbury, Sarah K; Sessions, Richard B; Mundell, Stuart J; Mumford, Andrew D

2016-05-01

Protease-activated receptor 4 (PAR4) is a key regulator of platelet reactivity and is encoded by F2RL3, which has abundant rare missense variants. We aimed to provide proof of principle that rare F2LR3 variants potentially affect platelet reactivity and responsiveness to PAR1 antagonist drugs and to explore underlying molecular mechanisms. We identified 6 rare F2RL3 missense variants in 236 cardiac patients, of which the variant causing a tyrosine 157 to cysteine substitution (Y157C) was predicted computationally to have the greatest effect on PAR4 structure. Y157C platelets from 3 cases showed reduced responses to PAR4-activating peptide and to α-thrombin compared with controls, but no reduction in responses to PAR1-activating peptide. Pretreatment with the PAR1 antagonist vorapaxar caused lower residual α-thrombin responses in Y157C platelets than in controls, indicating greater platelet inhibition. HEK293 cells transfected with a PAR4 Y157C expression construct had reduced PAR4 functional responses, unchanged total PAR4 expression but reduced surface expression. PAR4 Y157C was partially retained in the endoplasmic reticulum and displayed an expression pattern consistent with defective N-glycosylation. Mutagenesis of Y322, which is the putative hydrogen bond partner of Y157, also reduced PAR4 surface expression in HEK293 cells. Reduced PAR4 responses associated with Y157C result from aberrant anterograde surface receptor trafficking, in part, because of disrupted intramolecular hydrogen bonding. Characterization of PAR4 Y157C establishes that rare F2RL3 variants have the potential to markedly alter platelet PAR4 reactivity particularly after exposure to therapeutic PAR1 antagonists. © 2016 American Heart Association, Inc.

Plasma Channel Lenses and Plasma Tornadoes for Optical Beam Focusing and Transport

NASA Astrophysics Data System (ADS)

Hubbard, R. F.; Kaganovich, D.; Johnson, L. A.; Gordon, D. F.; Penano, J. R.; Hafizi, B.; Helle, M. H.; Mamonau, A. A.

2017-10-01

Shaped plasmas offer the possibility of manipulating laser pulses at intensities far above the damage limits for conventional optics. An example is the plasma channel, which is a cylindrical plasma column with an on-axis density minimum. Long plasma channels have been widely used to guide intense laser pulses, particularly in laser wakefield accelerators. A new concept, the ``plasma tornado'', offers the possibility of creating long plasma channels with no nearby structures and at densities lower than can be achieved by capillary discharges. A short plasma channel can focus a laser pulse in much the same manner as a conventional lens or off-axis parabola. When placed in front of the focal point of an intense laser pulse, a plasma channel lens (PCL) can reduce the effective f-number of conventional focusing optics. When placed beyond the focal point, it can act as a collimator. We will present experimental and modeling results for a new plasma tornado design, review experimental methods for generating short PCLs, and discuss potential applications. Supported by the Naval Research Laboratory Base Program.

Delivery of high energy Er:YAG pulsed laser light at 2.94 µm through a silica hollow core photonic crystal fibre.

PubMed

Urich, A; Maier, R R J; Mangan, B J; Renshaw, S; Knight, J C; Hand, D P; Shephard, J D

2012-03-12

In this paper the delivery of high power Er:YAG laser pulses through a silica hollow core photonic crystal fibre is demonstrated. The Er:YAG wavelength of 2.94 µm is well beyond the normal transmittance of bulk silica but the unique hollow core guidance allows silica to guide in this regime. We have demonstrated for the first time the ability to deliver high energy pulses through an all-silica fibre at 2.94 µm. These silica fibres are mechanically and chemically robust, biocompatible and have low sensitivity to bending. A maximum pulse energy of 14 mJ at 2.94 µm was delivered through the fibre. This, to our knowledge, is the first time a silica hollow core photonic crystal fibre has been shown to transmit 2.94 μm laser light at a fluence exceeding the thresholds required for modification (e.g. cutting and drilling) of hard biological tissue. Consequently, laser delivery systems based on these fibres have the potential for the realization of novel, minimally-invasive surgical procedures.

Discourse on pulse in medieval Persia--the Hidayat of Al-Akhawayni (?-983 A D.).

PubMed

Khodadoust, Kazem; Ardalan, Mohammadreza; Ghabili, Kamyar; Golzari, Samad E J; Eknoyan, Garabed

2013-06-20

In a period of compilation, original observations and expansion (900-1100 A.D.), Persians described new clinical manifestations of the diseases and expanded the earlier knowledge of materia medica. In the epoch of the Arabic language domination in the scientific literature of this period, advent of medical authors to write in Farsi shined in the Persian principalities. Akhawayani Bokhari was by far the most outstanding scholar of the time who wrote one of the earliest pandects of medicine of the period, the Hidayat al-Mutallimin fi al-Tibb (Learner's Guide to Medicine) in new Persian. The Hidayat is a relatively short and simplified digest of medicine at the time providing a glimpse of high level of medical education at the Samanid period (819-999). The present article is a translation of the sections of the Hidayat related to the pulse and its characters and conditions affecting the pulse in an attempt to increase our knowledge of the medicine, and particularly the pulse examination throughout the medieval era. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

PAR-2, LGL-1 and the CDC-42 GAP CHIN-1 act in distinct pathways to maintain polarity in the C. elegans embryo

PubMed Central

Beatty, Alexander; Morton, Diane G.; Kemphues, Kenneth

2013-01-01

In the one-cell C. elegans embryo, polarity is maintained by mutual antagonism between the anterior cortical proteins PAR-3, PKC-3, PAR-6 and CDC-42, and the posterior cortical proteins PAR-2 and LGL-1 on the posterior cortex. The mechanisms by which these proteins interact to maintain polarity are incompletely understood. In this study, we investigate the interplay among PAR-2, LGL-1, myosin, the anterior PAR proteins and CDC-42. We find that PAR-2 and LGL-1 affect cortical myosin accumulation by different mechanisms. LGL-1 does not directly antagonize the accumulation of cortical myosin and instead plays a role in regulating PAR-6 levels. By contrast, PAR-2 likely has separate roles in regulating cortical myosin accumulation and preventing the expansion of the anterior cortical domain. We also provide evidence that asymmetry of active CDC-42 can be maintained independently of LGL-1 and PAR-2 by a redundant pathway that includes the CDC-42 GAP CHIN-1. Finally, we show that, in addition to its primary role in regulating the size of the anterior cortical domain via its binding to PAR-6, CDC-42 has a secondary role in regulating cortical myosin that is not dependent on PAR-6. PMID:23536568

Specific and non-specific interactions of ParB with DNA: implications for chromosome segregation

PubMed Central

Taylor, James A.; Pastrana, Cesar L.; Butterer, Annika; Pernstich, Christian; Gwynn, Emma J.; Sobott, Frank; Moreno-Herrero, Fernando; Dillingham, Mark S.

2015-01-01

The segregation of many bacterial chromosomes is dependent on the interactions of ParB proteins with centromere-like DNA sequences called parS that are located close to the origin of replication. In this work, we have investigated the binding of Bacillus subtilis ParB to DNA in vitro using a variety of biochemical and biophysical techniques. We observe tight and specific binding of a ParB homodimer to the parS sequence. Binding of ParB to non-specific DNA is more complex and displays apparent positive co-operativity that is associated with the formation of larger, poorly defined, nucleoprotein complexes. Experiments with magnetic tweezers demonstrate that non-specific binding leads to DNA condensation that is reversible by protein unbinding or force. The condensed DNA structure is not well ordered and we infer that it is formed by many looping interactions between neighbouring DNA segments. Consistent with this view, ParB is also able to stabilize writhe in single supercoiled DNA molecules and to bridge segments from two different DNA molecules in trans. The experiments provide no evidence for the promotion of non-specific DNA binding and/or condensation events by the presence of parS sequences. The implications of these observations for chromosome segregation are discussed. PMID:25572315

Protease‐activated receptor 4: from structure to function and back again

PubMed Central

French, Shauna L

2016-01-01

Protease‐activated receptors are a family of four GPCRs (PAR1–PAR4) with a number of unique attributes. Nearly two and a half decades after the discovery of the first PAR, an antagonist targeting this receptor has been approved for human use. The first‐in‐class PAR1 antagonist, vorapaxar, was approved for use in the USA in 2014 for the prevention of thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial disease. These recent developments indicate the clinical potential of manipulating PAR function. While much work has been aimed at uncovering the function of PAR1 and, to a lesser extent, PAR2, comparatively little is known regarding the pharmacology and physiology of PAR3 and PAR4. Recent studies have begun to develop the pharmacological and genetic tools required to study PAR4 function in detail, and there is now emerging evidence for the function of PAR4 in disease settings. In this review, we detail the discovery, structure, pharmacology, physiological significance and therapeutic potential of PAR4. Linked Articles This article is part of a themed section on Molecular Pharmacology of G Protein‐Coupled Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.20/issuetoc PMID:26844674

PAR-2, LGL-1 and the CDC-42 GAP CHIN-1 act in distinct pathways to maintain polarity in the C. elegans embryo.

PubMed

Beatty, Alexander; Morton, Diane G; Kemphues, Kenneth

2013-05-01

In the one-cell C. elegans embryo, polarity is maintained by mutual antagonism between the anterior cortical proteins PAR-3, PKC-3, PAR-6 and CDC-42, and the posterior cortical proteins PAR-2 and LGL-1 on the posterior cortex. The mechanisms by which these proteins interact to maintain polarity are incompletely understood. In this study, we investigate the interplay among PAR-2, LGL-1, myosin, the anterior PAR proteins and CDC-42. We find that PAR-2 and LGL-1 affect cortical myosin accumulation by different mechanisms. LGL-1 does not directly antagonize the accumulation of cortical myosin and instead plays a role in regulating PAR-6 levels. By contrast, PAR-2 likely has separate roles in regulating cortical myosin accumulation and preventing the expansion of the anterior cortical domain. We also provide evidence that asymmetry of active CDC-42 can be maintained independently of LGL-1 and PAR-2 by a redundant pathway that includes the CDC-42 GAP CHIN-1. Finally, we show that, in addition to its primary role in regulating the size of the anterior cortical domain via its binding to PAR-6, CDC-42 has a secondary role in regulating cortical myosin that is not dependent on PAR-6.

A Conserved Mode of Protein Recognition and Binding in a ParD−ParE Toxin−Antitoxin Complex

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

Dalton, Kevin M.; Crosson, Sean

2010-05-06

Toxin-antitoxin (TA) systems form a ubiquitous class of prokaryotic proteins with functional roles in plasmid inheritance, environmental stress response, and cell development. ParDE family TA systems are broadly conserved on plasmids and bacterial chromosomes and have been well characterized as genetic elements that promote stable plasmid inheritance. We present a crystal structure of a chromosomally encoded ParD-ParE complex from Caulobacter crescentus at 2.6 {angstrom} resolution. This TA system forms an {alpha}{sub 2}{beta}{sub 2} heterotetramer in the crystal and in solution. The toxin-antitoxin binding interface reveals extensive polar and hydrophobic contacts of ParD antitoxin helices with a conserved recognition and bindingmore » groove on the ParE toxin. A cross-species comparison of this complex structure with related toxin structures identified an antitoxin recognition and binding subdomain that is conserved between distantly related members of the RelE/ParE toxin superfamily despite a low level of overall primary sequence identity. We further demonstrate that ParD antitoxin is dimeric, stably folded, and largely helical when not bound to ParE toxin. Thus, the paradigmatic model in which antitoxin undergoes a disorder-to-order transition upon toxin binding does not apply to this chromosomal ParD-ParE TA system.« less

Comparison between ultrasound-guided interfascial pulsed radiofrequency and ultrasound-guided interfascial block with local anesthetic in myofascial pain syndrome of trapezius muscle

PubMed Central

Cho, Ik Tae; Cho, Yun Woo; Kwak, Sang Gyu; Chang, Min Cheol

2017-01-01

Abstract Myofascial pain syndrome (MPS) of the trapezius muscle (TM) is a frequently occurring musculoskeletal disorder. However, the treatment of MPS of the TM remains a challenge. We investigated the effects of ultrasound (US)-guided pulsed radiofrequency (PRF) stimulation on the interfascial area of the TM. In addition, we compared its effect with that of interfascial block (IFB) with 10 mL of 0.6% lidocaine on the interfascial area of the TM. Thirty-six patients with MPS of the TM were included and randomly assigned into 2 groups. Eighteen patients underwent PRF stimulation on the interfascial area of the TM (PRF group) and 18 patients underwent IFB with lidocaine on the same area (IFB group). Pain intensity was evaluated using a numerical rating scale (NRS) at pretreatment, 2, 4, and 8 weeks after treatment. At pretreatment and 8 weeks after treatment, quality of life was assessed using the Short Form-36 Health Survey (SF-36), which includes the physical component score (PCS) and the mental component score (MCS). One patient in the PRF group was lost to follow-up. Patients in both groups showed a significant decrease in NRS scores at 2, 4, and 8 weeks after treatments and a significant increase in PCS and MCS of the SF-36 at 8 weeks after treatments. Two weeks after each treatment, the decrements of NRS scores were not significantly different between the 2 groups. However, 4 and 8 weeks after the procedures, we found that the NRS score was significantly lower in the PRF group than in the IFB group. At 8 weeks after the treatments, PCS and MCS of the SF-36 in the PRF group were significantly higher than those in the IFB group. For the management of MPS of the TM, US-guided interfascial PRF had a better long-term effect on reducing the pain and the quality of life compared to US-guided IFB. Therefore, we think US-guided PRF stimulation on the interfascial area of the TM can be a beneficial alternative to manage the pain following MPS of the TM. PMID:28151904

Comparison between ultrasound-guided interfascial pulsed radiofrequency and ultrasound-guided interfascial block with local anesthetic in myofascial pain syndrome of trapezius muscle.

PubMed

Cho, Ik Tae; Cho, Yun Woo; Kwak, Sang Gyu; Chang, Min Cheol

2017-02-01

Myofascial pain syndrome (MPS) of the trapezius muscle (TM) is a frequently occurring musculoskeletal disorder. However, the treatment of MPS of the TM remains a challenge. We investigated the effects of ultrasound (US)-guided pulsed radiofrequency (PRF) stimulation on the interfascial area of the TM. In addition, we compared its effect with that of interfascial block (IFB) with 10 mL of 0.6% lidocaine on the interfascial area of the TM. Thirty-six patients with MPS of the TM were included and randomly assigned into 2 groups. Eighteen patients underwent PRF stimulation on the interfascial area of the TM (PRF group) and 18 patients underwent IFB with lidocaine on the same area (IFB group). Pain intensity was evaluated using a numerical rating scale (NRS) at pretreatment, 2, 4, and 8 weeks after treatment. At pretreatment and 8 weeks after treatment, quality of life was assessed using the Short Form-36 Health Survey (SF-36), which includes the physical component score (PCS) and the mental component score (MCS). One patient in the PRF group was lost to follow-up. Patients in both groups showed a significant decrease in NRS scores at 2, 4, and 8 weeks after treatments and a significant increase in PCS and MCS of the SF-36 at 8 weeks after treatments. Two weeks after each treatment, the decrements of NRS scores were not significantly different between the 2 groups. However, 4 and 8 weeks after the procedures, we found that the NRS score was significantly lower in the PRF group than in the IFB group. At 8 weeks after the treatments, PCS and MCS of the SF-36 in the PRF group were significantly higher than those in the IFB group. For the management of MPS of the TM, US-guided interfascial PRF had a better long-term effect on reducing the pain and the quality of life compared to US-guided IFB. Therefore, we think US-guided PRF stimulation on the interfascial area of the TM can be a beneficial alternative to manage the pain following MPS of the TM.

Kallikrein-related peptidase 4 (KLK4) initiates intracellular signaling via protease-activated receptors (PARs). KLK4 and PAR-2 are co-expressed during prostate cancer progression.

PubMed

Ramsay, Andrew J; Dong, Ying; Hunt, Melanie L; Linn, MayLa; Samaratunga, Hemamali; Clements, Judith A; Hooper, John D

2008-05-02

Kallikrein-related peptidase 4 (KLK4) is one of the 15 members of the human KLK family and a trypsin-like, prostate cancer-associated serine protease. Signaling initiated by trypsin-like serine proteases are transduced across the plasma membrane primarily by members of the protease-activated receptor (PAR) family of G protein-coupled receptors. Here we show, using Ca(2+) flux assays, that KLK4 signals via both PAR-1 and PAR-2 but not via PAR-4. Dose-response analysis over the enzyme concentration range 0.1-1000 nM indicated that KLK4-induced Ca(2+) mobilization via PAR-1 is more potent than via PAR-2, whereas KLK4 displayed greater efficacy via the latter PAR. We confirmed the specificity of KLK4 signaling via PAR-2 using in vitro protease cleavage assays and anti-phospho-ERK1/2/total ERK1/2 Western blot analysis of PAR-2-overexpressing and small interfering RNA-mediated receptor knockdown cell lines. Consistently, confocal microscopy analyses indicated that KLK4 initiates loss of PAR-2 from the cell surface and receptor internalization. Immunohistochemical analysis indicated the co-expression of agonist and PAR-2 in primary prostate cancer and bone metastases, suggesting that KLK4 signaling via this receptor will have pathological relevance. These data provide insight into KLK4-mediated cell signaling and suggest that signals induced by this enzyme via PARs may be important in prostate cancer.

Par-4-mediated recruitment of Amida to the actin cytoskeleton leads to the induction of apoptosis

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

Boosen, Meike; Vetterkind, Susanne; Koplin, Ansgar

Par-4 (prostate apoptosis response-4) sensitizes cells to apoptotic stimuli, but the exact mechanisms are still poorly understood. Using Par-4 as bait in a yeast two-hybrid screen, we identified Amida as a novel interaction partner, a ubiquitously expressed protein which has been suggested to be involved in apoptotic processes. Complex formation of Par-4 and Amida occurs in vitro and in vivo and is mediated via the C-termini of both proteins, involving the leucine zipper of Par-4. Amida resides mainly in the nucleus but displays nucleo-cytoplasmic shuttling in heterokaryons. Upon coexpression with Par-4 in REF52.2 cells, Amida translocates to the cytoplasm andmore » is recruited to actin filaments by Par-4, resulting in enhanced induction of apoptosis. The synergistic effect of Amida/Par-4 complexes on the induction of apoptosis is abrogated when either Amida/Par-4 complex formation or association of these complexes with the actin cytoskeleton is impaired, indicating that the Par-4-mediated relocation of Amida to the actin cytoskeleton is crucial for the pro-apoptotic function of Par-4/Amida complexes in REF52.2 cells. The latter results in enhanced phosphorylation of the regulatory light chain of myosin II (MLC) as has previously been shown for Par-4-mediated recruitment of DAP-like kinase (Dlk), suggesting that the recruitment of nuclear proteins involved in the regulation of apoptotic processes to the actin filament system by Par-4 represents a potent mechanism how Par-4 can trigger apoptosis.« less

Brownian Ratchet Mechanism for Faithful Segregation of Low-Copy-Number Plasmids.

PubMed

Hu, Longhua; Vecchiarelli, Anthony G; Mizuuchi, Kiyoshi; Neuman, Keir C; Liu, Jian

2017-04-11

Bacterial plasmids are extrachromosomal DNA that provides selective advantages for bacterial survival. Plasmid partitioning can be remarkably robust. For high-copy-number plasmids, diffusion ensures that both daughter cells inherit plasmids after cell division. In contrast, most low-copy-number plasmids need to be actively partitioned by a conserved tripartite ParA-type system. ParA is an ATPase that binds to chromosomal DNA; ParB is the stimulator of the ParA ATPase and specifically binds to the plasmid at a centromere-like site, parS. ParB stimulation of the ParA ATPase releases ParA from the bacterial chromosome, after which it takes a long time to reset its DNA-binding affinity. We previously demonstrated in vitro that the ParA system can exploit this biochemical asymmetry for directed cargo transport. Multiple ParA-ParB bonds can bridge a parS-coated cargo to a DNA carpet, and they can work collectively as a Brownian ratchet that directs persistent cargo movement with a ParA-depletion zone trailing behind. By extending this model, we suggest that a similar Brownian ratchet mechanism recapitulates the full range of actively segregated plasmid motilities observed in vivo. We demonstrate that plasmid motility is tuned as the replenishment rate of the ParA-depletion zone progressively increases relative to the cargo speed, evolving from diffusion to pole-to-pole oscillation, local excursions, and, finally, immobility. When the plasmid replicates, the daughters largely display motilities similar to that of their mother, except that when the single-focus progenitor is locally excursive, the daughter foci undergo directed segregation. We show that directed segregation maximizes the fidelity of plasmid partition. Given that local excursion and directed segregation are the most commonly observed modes of plasmid motility in vivo, we suggest that the operation of the ParA-type partition system has been shaped by evolution for high fidelity of plasmid segregation. Published by Elsevier Inc.

Vaporization and recondensation dynamics of indocyanine green-loaded perfluoropentane droplets irradiated by a short pulse laser

NASA Astrophysics Data System (ADS)

Yu, Jaesok; Chen, Xucai; Villanueva, Flordeliza S.; Kim, Kang

2016-12-01

Phase-transition droplets have been proposed as promising contrast agents for ultrasound and photoacoustic imaging. Short pulse laser activated perfluorocarbon-based droplets, especially when in a medium with a temperature below their boiling point, undergo phase changes of vaporization and recondensation in response to pulsed laser irradiation. Here, we report and discuss the vaporization and recondensation dynamics of perfluoropentane droplets containing indocyanine green in response to a short pulsed laser with optical and acoustic measurements. To investigate the effect of temperature on the vaporization process, an imaging chamber was mounted on a temperature-controlled water reservoir and then the vaporization event was recorded at 5 million frames per second via a high-speed camera. The high-speed movies show that most of the droplets within the laser beam area expanded rapidly as soon as they were exposed to the laser pulse and immediately recondensed within 1-2 μs. The vaporization/recondensation process was consistently reproduced in six consecutive laser pulses to the same area. As the temperature of the media was increased above the boiling point of the perfluoropentane, the droplets were less likely to recondense and remained in a gas phase after the first vaporization. These observations will help to clarify the underlying processes and eventually guide the design of repeatable phase-transition droplets as a photoacoustic imaging contrast agent.

The Sterilization Effect of Cooperative Treatment of High Voltage Electrostatic Field and Variable Frequency Pulsed Electromagnetic Field on Heterotrophic Bacteria in Circulating Cooling Water

NASA Astrophysics Data System (ADS)

Gao, Xuetong; Liu, Zhian; Zhao, Judong

2018-01-01

Compared to other treatment of industrial circulating cooling water in the field of industrial water treatment, high-voltage electrostatic field and variable frequency pulsed electromagnetic field co-sterilization technology, an advanced technology, is widely used because of its special characteristics--low energy consumption, nonpoisonous and environmentally friendly. In order to get a better cooling water sterilization effect under the premise of not polluting the environment, some experiments about sterilization of heterotrophic bacteria in industrial circulating cooling water by cooperative treatment of high voltage electrostatic field and variable frequency pulsed electromagnetic field were carried out. The comparison experiment on the sterilization effect of high-voltage electrostatic field and variable frequency pulsed electromagnetic field co-sterilization on heterotrophic bacteria in industrial circulating cooling water was carried out by change electric field strength and pulse frequency. The results show that the bactericidal rate is selective to the frequency and output voltage, and the heterotrophic bacterium can only kill under the condition of sweep frequency range and output voltage. When the voltage of the high voltage power supply is 4000V, the pulse frequency is 1000Hz and the water temperature is 30°C, the sterilization rate is 48.7%, the sterilization rate is over 90%. Results of this study have important guiding significance for future application of magnetic field sterilization.

Pulsed radiofrequency on radial nerve under ultrasound guidance for treatment of intractable lateral epicondylitis.

PubMed

Oh, Dae Seok; Kang, Tae Hyung; Kim, Hyae Jin

2016-06-01

Lateral epicondylitis is a painful and functionally limiting disorder. Although lateral elbow pain is generally self-limiting, in a minority of people symptoms persist for a long time. When various conservative treatments fail, surgical approach is recommended. Surgical denervation of several nerves that innervate the lateral humeral epicondyle could be considered in patients with refractory pain because it denervates the region of pain. Pulsed radiofrequency is a minimally invasive procedure that improves chronic pain when applied to various neural tissues without causing any significant destruction and painful complication. This procedure is safe, minimally invasive, and has less risk of complications relatively compared to the surgical approach. The radial nerve can be identified as a target for pulsed radiofrequency lesioning in lateral epicondylitis. This innovative method of pulsed radiofrequency applied to the radial nerve has not been reported before. We reported on two patients with intractable lateral epicondylitis suffering from elbow pain who did not respond to nonoperative treatments, but in whom the ultrasound-guided pulsed radiofrequency neuromodulation of the radial nerve induced symptom improvement. After a successful diagnostic nerve block, radiofrequency probe adjustment around the radial nerve was performed on the lateral aspect of the distal upper arm under ultrasound guidance and multiple pulsed treatments were applied. A significant reduction in pain was reported over the follow-up period of 12 weeks.

Neutron optics concept for the materials engineering diffractometer at the ESS

NASA Astrophysics Data System (ADS)

Šaroun, J.; Fenske, J.; Rouijaa, M.; Beran, P.; Navrátil, J.; Lukáš, P.; Schreyer, A.; Strobl, M.

2016-09-01

The Beamline for European Materials Engineering Research (BEER) has been recently proposed to be built at the European Spallation Source (ESS). The presented concept of neutron delivery optics for this instrument addresses the problems of bi-spectral beam extraction from a small moderator, optimization of neutron guides profile for long-range neutron transport and focusing at the sample under various constraints. They include free space before and after the guides, a narrow guide section with gaps for choppers, closing of direct line of sight and cost reduction by optimization of the guides cross-section and coating. A system of slits and exchangeable focusing optics is proposed in order to match various wavelength resolution options provided by the pulse shaping and modulation choppers, which permits to efficiently trade resolution for intensity in a wide range. Simulated performance characteristics such as brilliance transfer ratio are complemented by the analysis of the histories of “useful” neutrons obtained by back tracing neutrons hitting the sample, which helps to optimize some of the neutron guide parameters such as supermirror coating.

A detailed examination of the LWFA in the Self-Guided Nonlinear Blowout Regime for 15-100 Joule Lasers

NASA Astrophysics Data System (ADS)

Davidson, Asher; Tableman, Adam; Yu, Peicheng; An, Weiming; Tsung, Frank; Mori, Warren; Lu, Wei; Fonseca, Ricardo

2017-10-01

We examine scaling laws for LWFA in the regime nonlinear, self-guided regime in detail using the quasi-3D version of the particle-in-cell code OSIRIS. We find that the scaling laws continue to work well when we fix the normalized laser amplitude while reducing plasma density. It is further found that the energy gain for fixed laser energy can be improved by shortening the pulse length until self-guiding almost no longer occurs and that the energy gain can be optimized by using lasers with asymmetric longitudinal profiles. We find that when optimized, a 15 J laser may yield particle energies as high as 5.3 GeV without the need of any external guiding. Detailed studies for optimizing energy gains from 30 J and 100 J lasers will also presented which indicate that energies in excess of 10 GeV can be possible in the near term without the need for external guiding. This work is supported by the NSF and DOE.

The role of pars flaccida in human middle ear sound transmission.

PubMed

Aritomo, H; Goode, R L; Gonzalez, J

1988-04-01

The role of the pars flaccida in middle ear sound transmission was studied with the use of twelve otoscopically normal, fresh, human temporal bones. Peak-to-peak umbo displacement in response to a constant sound pressure level at the tympanic membrane was measured with a noncontacting video measuring system capable of repeatable measurements down to 0.2 micron. Measurements were made before and after pars flaccida modifications at 18 frequencies between 100 and 4000 Hz. Four pars flaccida modifications were studied: (1) acoustic insulation of the pars flaccida to the ear canal with a silicone rubber baffle, (2) stiffening the pars flaccida with cyanoacrylate cement, (3) decreasing the tension of the pars flaccida with a nonperforating incision, and (4) perforation of the pars flaccida. All of the modifications (except the perforation) had a minimal effect on umbo displacement; this seems to imply that the pars flaccida has a minor acoustic role in human beings.

Dimerization controls the lipid raft partitioning of uPAR/CD87 and regulates its biological functions

PubMed Central

Cunningham, Orla; Andolfo, Annapaola; Santovito, Maria Lisa; Iuzzolino, Lucia; Blasi, Francesco; Sidenius, Nicolai

2003-01-01

The urokinase-type plasminogen activator receptor (uPAR/CD87) is a glycosylphosphatidylinositol-anchored membrane protein with multiple functions in extracellular proteolysis, cell adhesion, cell migration and proliferation. We now report that cell surface uPAR dimerizes and that dimeric uPAR partitions preferentially to detergent-resistant lipid rafts. Dimerization of uPAR did not require raft partitioning as the lowering of membrane cholesterol failed to reduce dimerization and as a transmembrane uPAR chimera, which does not partition to lipid rafts, also dimerized efficiently. While uPA bound to uPAR independently of its membrane localization and dimerization status, uPA-induced uPAR cleavage was strongly accelerated in lipid rafts. In contrast to uPA, the binding of Vn occurred preferentially to raft- associated dimeric uPAR and was completely blocked by cholesterol depletion. PMID:14609946

Structures of actin-like ParM filaments show architecture of plasmid-segregating spindles.

PubMed

Bharat, Tanmay A M; Murshudov, Garib N; Sachse, Carsten; Löwe, Jan

2015-07-02

Active segregation of Escherichia coli low-copy-number plasmid R1 involves formation of a bipolar spindle made of left-handed double-helical actin-like ParM filaments. ParR links the filaments with centromeric parC plasmid DNA, while facilitating the addition of subunits to ParM filaments. Growing ParMRC spindles push sister plasmids to the cell poles. Here, using modern electron cryomicroscopy methods, we investigate the structures and arrangements of ParM filaments in vitro and in cells, revealing at near-atomic resolution how subunits and filaments come together to produce the simplest known mitotic machinery. To understand the mechanism of dynamic instability, we determine structures of ParM filaments in different nucleotide states. The structure of filaments bound to the ATP analogue AMPPNP is determined at 4.3 Å resolution and refined. The ParM filament structure shows strong longitudinal interfaces and weaker lateral interactions. Also using electron cryomicroscopy, we reconstruct ParM doublets forming antiparallel spindles. Finally, with whole-cell electron cryotomography, we show that doublets are abundant in bacterial cells containing low-copy-number plasmids with the ParMRC locus, leading to an asynchronous model of R1 plasmid segregation.

A three-dimensional ParF meshwork assembles through the nucleoid to mediate plasmid segregation

PubMed Central

McLeod, Brett N.; Allison-Gamble, Gina E.; Barge, Madhuri T.; Tonthat, Nam K.; Schumacher, Maria A.; Hayes, Finbarr

2017-01-01

Abstract Genome segregation is a fundamental step in the life cycle of every cell. Most bacteria rely on dedicated DNA partition proteins to actively segregate chromosomes and low copy-number plasmids. Here, by employing super resolution microscopy, we establish that the ParF DNA partition protein of the ParA family assembles into a three-dimensional meshwork that uses the nucleoid as a scaffold and periodically shuttles between its poles. Whereas ParF specifies the territory for plasmid trafficking, the ParG partner protein dictates the tempo of ParF assembly cycles and plasmid segregation events by stimulating ParF adenosine triphosphate hydrolysis. Mutants in which this ParG temporal regulation is ablated show partition deficient phenotypes as a result of either altered ParF structure or dynamics and indicate that ParF nucleoid localization and dynamic relocation, although necessary, are not sufficient per se to ensure plasmid segregation. We propose a Venus flytrap model that merges the concepts of ParA polymerization and gradient formation and speculate that a transient, dynamic network of intersecting polymers that branches into the nucleoid interior is a widespread mechanism to distribute sizeable cargos within prokaryotic cells. PMID:28034957

Estimation of photosynthetically available radiation (PAR) from OCEANSAT-I OCM using a simple atmospheric radiative transfer model

NASA Astrophysics Data System (ADS)

Tripathy, Madhumita; Raman, Mini; Chauhan, Prakash

2015-10-01

Photosynthetically available radiation (PAR) is an important variable for radiation budget, marine and terrestrial ecosystem models. OCEANSAT-1 Ocean Color Monitor (OCM) PAR was estimated using two different methods under both clear and cloudy sky conditions. In the first approach, aerosol optical depth (AOD) and cloud optical depth (COD) were estimated from OCEANSAT-1 OCM TOA (top-of-atmosphere) radiance data on a pixel by pixel basis and PAR was estimated from extraterrestrial solar flux for fifteen spectral bands using a radiative transfer model. The second approach used TOA radiances measured by OCM in the PAR spectral range to compute PAR. This approach also included surface albedo and cloud albedo as inputs. Comparison between OCEANSAT-1 OCM PAR at noon with in situ measured PAR shows that root mean square difference was 5.82% for the method I and 7.24% for the method II in daily time scales. Results indicate that methodology adopted to estimate PAR from OCEANSAT-1 OCM can produce reasonably accurate PAR estimates over the tropical Indian Ocean region. This approach can be extended to OCEANSAT-2 OCM and future OCEANSAT-3 OCM data for operational estimation of PAR for regional marine ecosystem applications.

Factor X/Xa elicits protective signaling responses in endothelial cells directly via PAR-2 and indirectly via endothelial protein C receptor-dependent recruitment of PAR-1.

PubMed

Bae, Jong-Sup; Yang, Likui; Rezaie, Alireza R

2010-11-05

We recently demonstrated that the Gla domain-dependent interaction of protein C with endothelial protein C receptor (EPCR) leads to dissociation of the receptor from caveolin-1 and recruitment of PAR-1 to a protective signaling pathway. Thus, the activation of PAR-1 by either thrombin or PAR-1 agonist peptide elicited a barrier-protective response if endothelial cells were preincubated with protein C. In this study, we examined whether other vitamin K-dependent coagulation protease zymogens can modulate PAR-dependent signaling responses in endothelial cells. We discovered that the activation of both PAR-1 and PAR-2 in endothelial cells pretreated with factor FX (FX)-S195A, but not other procoagulant protease zymogens, also results in initiation of protective intracellular responses. Interestingly, similar to protein C, FX interaction with endothelial cells leads to dissociation of EPCR from caveolin-1 and recruitment of PAR-1 to a protective pathway. Further studies revealed that, FX activated by factor VIIa on tissue factor bearing endothelial cells also initiates protective signaling responses through the activation of PAR-2 independent of EPCR mobilization. All results could be recapitulated by the receptor agonist peptides to both PAR-1 and PAR-2. These results suggest that a cross-talk between EPCR and an unknown FX/FXa receptor, which does not require interaction with the Gla domain of FX, recruits PAR-1 to protective signaling pathways in endothelial cells.

Cross-talk between toll-like receptor 4 (TLR4) and proteinase-activated receptor 2 (PAR(2) ) is involved in vascular function.

PubMed

Bucci, M; Vellecco, V; Harrington, L; Brancaleone, V; Roviezzo, F; Mattace Raso, G; Ianaro, A; Lungarella, G; De Palma, R; Meli, R; Cirino, G

2013-01-01

Proteinase-activated receptors (PARs) and toll-like receptors (TLRs) are involved in innate immune responses. The aim of this study was to evaluate the possible cross-talk between PAR(2) and TLR4 in vessels in physiological condition and how it varies following stimulation of TLR4 by using in vivo and ex vivo models. Thoracic aortas were harvested from both naïve and endotoxaemic rats for in vitro studies. Arterial blood pressure was monitored in anaesthetized rats in vivo. LPS was used as a TLR4 agonist while PAR(2) activating peptide (AP) was used as a PAR(2) agonist. Aortas harvested from TLR4(-/-) mice were also used to characterize the PAR(2) response. PAR(2) , but not TLR4, expression was enhanced in aortas of endotoxaemic rats. PAR(2) AP-induced vasorelaxation was increased in aortic rings of LPS-treated rats. TLR4 inhibitors, curcumine and resveratrol, reduced PAR(2) AP-induced vasorelaxation and PAR(2) AP-induced hypotension in both naïve and endotoxaemic rats. Finally, in aortic rings from TLR4(-/-) mice, the expression of PAR(2) was reduced and the PAR(2) AP-induced vasodilatation impaired compared with those from wild-type mice and both resveratrol and curcumine were ineffective. Cross-talk between PAR(2) and TLR4 contributes to vascular homeostasis. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Cross-talk between toll-like receptor 4 (TLR4) and proteinase-activated receptor 2 (PAR2) is involved in vascular function

PubMed Central

Bucci, M; Vellecco, V; Harrington, L; Brancaleone, V; Roviezzo, F; Mattace Raso, G; Ianaro, A; Lungarella, G; De Palma, R; Meli, R; Cirino, G

2013-01-01

Background and Purpose Proteinase-activated receptors (PARs) and toll-like receptors (TLRs) are involved in innate immune responses. The aim of this study was to evaluate the possible cross-talk between PAR2 and TLR4 in vessels in physiological condition and how it varies following stimulation of TLR4 by using in vivo and ex vivo models. Experimental Approach Thoracic aortas were harvested from both naïve and endotoxaemic rats for in vitro studies. Arterial blood pressure was monitored in anaesthetized rats in vivo. LPS was used as a TLR4 agonist while PAR2 activating peptide (AP) was used as a PAR2 agonist. Aortas harvested from TLR4–/– mice were also used to characterize the PAR2 response. Key Results PAR2, but not TLR4, expression was enhanced in aortas of endotoxaemic rats. PAR2AP-induced vasorelaxation was increased in aortic rings of LPS-treated rats. TLR4 inhibitors, curcumine and resveratrol, reduced PAR2AP-induced vasorelaxation and PAR2AP-induced hypotension in both naïve and endotoxaemic rats. Finally, in aortic rings from TLR4–/– mice, the expression of PAR2 was reduced and the PAR2AP-induced vasodilatation impaired compared with those from wild-type mice and both resveratrol and curcumine were ineffective. Conclusions and Implications Cross-talk between PAR2 and TLR4 contributes to vascular homeostasis. PMID:22957757

PAR2 (Protease-Activated Receptor 2) Deficiency Attenuates Atherosclerosis in Mice.

PubMed

Jones, Shannon M; Mann, Adrien; Conrad, Kelsey; Saum, Keith; Hall, David E; McKinney, Lisa M; Robbins, Nathan; Thompson, Joel; Peairs, Abigail D; Camerer, Eric; Rayner, Katey J; Tranter, Michael; Mackman, Nigel; Owens, A Phillip

2018-06-01

PAR2 (protease-activated receptor 2)-dependent signaling results in augmented inflammation and has been implicated in the pathogenesis of several autoimmune conditions. The objective of this study was to determine the effect of PAR2 deficiency on the development of atherosclerosis. PAR2 mRNA and protein expression is increased in human carotid artery and mouse aortic arch atheroma versus control carotid and aortic arch arteries, respectively. To determine the effect of PAR2 deficiency on atherosclerosis, male and female low-density lipoprotein receptor-deficient ( Ldlr -/- ) mice (8-12 weeks old) that were Par2 +/+ or Par2 -/- were fed a fat- and cholesterol-enriched diet for 12 or 24 weeks. PAR2 deficiency attenuated atherosclerosis in the aortic sinus and aortic root after 12 and 24 weeks. PAR2 deficiency did not alter total plasma cholesterol concentrations or lipoprotein distributions. Bone marrow transplantation showed that PAR2 on nonhematopoietic cells contributed to atherosclerosis. PAR2 deficiency significantly attenuated levels of the chemokines Ccl2 and Cxcl1 in the circulation and macrophage content in atherosclerotic lesions. Mechanistic studies using isolated primary vascular smooth muscle cells showed that PAR2 deficiency is associated with reduced Ccl2 and Cxcl1 mRNA expression and protein release into the supernatant resulting in less monocyte migration. Our results indicate that PAR2 deficiency is associated with attenuation of atherosclerosis and may reduce lesion progression by blunting Ccl2 - and Cxcl1 -induced monocyte infiltration. © 2018 American Heart Association, Inc.

Classical and low-light-level detection and pulse characterization using optical-frequency mixers

NASA Astrophysics Data System (ADS)

Langrock, Carsten

2007-12-01

Classical all-optical signal processing for telecommunication applications greatly benefits from the availability of highly efficient optical frequency (OF) mixers, the optical analogue of radio-frequency mixers used in RF signal processing. The OF mixers presented in this dissertation are based on reverse-proton-exchange (RPE) periodically-poled lithium niobate (PPLN) waveguides, one of the most efficient and versatile material systems in the field of nonlinear optics to date. Taking advantage of fabrication technologies developed in Prof. Martin Fejer's group over the past two decades, we expand the range of applications for these OF mixers to low-light-level signal detection and pulse characterization. We demonstrate high-speed high-efficiency single-photon counting at telecommunication wavelengths, used for the implementation of record-breaking quantum-key distribution systems, which allow unconditionally secure data transfer. In collaboration with researchers at the MIT Lincoln Laboratory, we also show that the very same technology can be used to achieve an order of magnitude improvement in the sensitivity of classical few-photon free-space communication links based on pulse-position modulation. These extremely sensitive receivers (1 photon/bit) are being developed to facilitate deep-space communication over several hundred million kilometers between Mars and Earth. OF mixers can also be used to fully characterize, potentially weak, ultrashort pulses, as well as time-magnify segments of ultra-high-speed data streams to be detected in real time by conventional streak cameras and oscilloscopes. We will present a novel implementation of both collinear autocorrelation as well as parametric temporal imaging (in collaboration with the Lawrence Livermore National Laboratory) based on mode-multiplexing in integrated asymmetric Y-junctions in combination with linearly-chirped apodized quasi-phasematching gratings. For the first time, background-free autocorrelation, frequency-resolved optical gating, and temporal imaging can be realized in single-polarization-guiding collinear waveguide structures at sub-60-aJ (400 photons/pulse) levels. Recently, guided-wave OF mixers have also become important for precision metrology applications based on frequency-comb generation (FCG) (i.e. optical ruler) using ultrashort pulses. The most compact and energy efficient FCG systems use fiber lasers. In collaboration with IMRA America, Inc., we demonstrate that RPE PPLN waveguides can be used to implement fully integrated fiber-laser-based FCG systems taking advantage of unprecedented octave-spanning spectral broadening of the input pulses in combination with simultaneous phase sensing inside the same waveguide.

Resistance to Plum Pox Virus (PPV) in apricot (Prunus armeniaca L.) is associated with down-regulation of two MATHd genes.

PubMed

Zuriaga, Elena; Romero, Carlos; Blanca, Jose Miguel; Badenes, Maria Luisa

2018-01-27

Plum pox virus (PPV), causing Sharka disease, is one of the main limiting factors for Prunus production worldwide. In apricot (Prunus armeniaca L.) the major PPV resistance locus (PPVres), comprising ~ 196 kb, has been mapped to the upper part of linkage group 1. Within the PPVres, 68 genomic variants linked in coupling to PPV resistance were identified within 23 predicted transcripts according to peach genome annotation. Taking into account the predicted functions inferred from sequence homology, some members of a cluster of meprin and TRAF-C homology domain (MATHd)-containing genes were pointed as PPV resistance candidate genes. Here, we have characterized the global apricot transcriptome response to PPV-D infection identifying six PPVres locus genes (ParP-1 to ParP-6) differentially expressed in resistant/susceptible cultivars. Two of them (ParP-3 and ParP-4), that encode MATHd proteins, appear clearly down-regulated in resistant cultivars, as confirmed by qRT-PCR. Concurrently, variant calling was performed using whole-genome sequencing data of 24 apricot cultivars (10 PPV-resistant and 14 PPV-susceptible) and 2 wild relatives (PPV-susceptible). ParP-3 and ParP-4, named as Prunus armeniaca PPVres MATHd-containing genes (ParPMC), are the only 2 genes having allelic variants linked in coupling to PPV resistance. ParPMC1 has 1 nsSNP, while ParPMC2 has 15 variants, including a 5-bp deletion within the second exon that produces a frameshift mutation. ParPMC1 and ParPMC2 are adjacent and highly homologous (87.5% identity) suggesting they are paralogs originated from a tandem duplication. Cultivars carrying the ParPMC2 resistant (mutated) allele show lack of expression in both ParPMC2 and especially ParPMC1. Accordingly, we hypothesize that ParPMC2 is a pseudogene that mediates down-regulation of its functional paralog ParPMC1 by silencing. As a whole, results strongly support ParPMC1 and/or ParPMC2 as host susceptibility genes required for PPV infection which silencing may confer PPV resistance trait. This finding may facilitate resistance breeding by marker-assisted selection and pave the way for gene edition approaches in Prunus.

Protease Activated Receptor-2 Expression and Function in Asthmatic Bronchial Smooth Muscle

PubMed Central

Gilbert, Guillaume; Carvalho, Gabrielle; Trian, Thomas; Ozier, Annaig; Gillibert-Duplantier, Jennifer; Ousova, Olga; Maurat, Elise; Thumerel, Matthieu; Quignard, Jean-François; Girodet, Pierre-Olivier; Marthan, Roger; Berger, Patrick

2014-01-01

Asthmatic bronchial smooth muscle (BSM) is characterized by structural remodeling associated with mast cell infiltration displaying features of chronic degranulation. Mast cell-derived tryptase can activate protease activated receptor type-2 (PAR-2) of BSM cells. The aims of the present study were (i) to evaluate the expression of PAR-2 in both asthmatic and non asthmatic BSM cells and, (ii) to analyze the effect of prolonged stimulation of PAR-2 in asthmatic BSM cells on cell signaling and proliferation. BSM cells were obtained from both 33 control subjects and 22 asthmatic patients. PAR-2 expression was assessed by flow cytometry, western blot and quantitative RT-PCR. Calcium response, transduction pathways and proliferation were evaluated before and following PAR-2 stimulation by SLIGKV-NH2 or trypsin for 1 to 3 days. Asthmatic BSM cells expressed higher basal levels of functional PAR-2 compared to controls in terms of mRNA, protein expression and calcium response. When PAR-2 expression was increased by means of lentivirus in control BSM cells to a level similar to that of asthmatic cells, PAR-2-induced calcium response was then similar in both types of cell. However, repeated PAR-2 stimulations increased the proliferation of asthmatic BSM cells but not that of control BSM cells even following lentiviral over-expression of PAR-2. Such an increased proliferation was related to an increased phosphorylation of ERK in asthmatic BSM cells. In conclusion, we have demonstrated that asthmatic BSM cells express increased baseline levels of functional PAR-2. This higher basal level of PAR-2 accounts for the increased calcium response to PAR-2 stimulation, whereas the increased proliferation to repeated PAR-2 stimulation is related to increased ERK phosphorylation. PMID:24551046

Increased Expression of Cathelicidin by Direct Activation of Protease-Activated Receptor 2: Possible Implications on the Pathogenesis of Rosacea

PubMed Central

Kim, Ji Young; Kim, Yoon Jee; Lim, Beom Jin; Sohn, Hyo Jung; Shin, Dongyun

2014-01-01

Purpose Recent findings of increased cathelicidin protein and its proteolytic fragments in rosacea suggest a pathogenic role for cathelicidin in this disease. The relationship between cathelicidin and protease-activated receptor 2 (PAR-2) is therefore of interest, as PAR-2, expressed principally in keratinocytes, regulates pro-inflammatory cytokine expression in the skin. The purpose of this study was to determine the relationship between expression of PAR-2 and cathelicidin in rosacea and to test the effect of direct PAR-2 activation on cathelicidin expression in keratinocytes. Materials and Methods Samples from 40 patients with clinicopathologic diagnosis of rosacea and facial skin tissue samples from 20 patients with no specific findings or milium without inflammation were retrieved. Intensities of immunohistochemical staining for PAR-2 and cathelicidin were compared between normal and rosacea-affected skin tissues. Additionally, correlations between PAR-2 and cathelicidin staining intensities within rosacea patients were analyzed. In cultured keratinocytes, changes in PAR-2, cathelicidin, and vascular endothelial growth factor (VEGF) mRNA and protein were analyzed after treatment with PAR-2 activating peptide (AP). Results Cathelicidin expression was significantly higher in rosacea skin tissues than in normal tissues (p<0.001), while PAR-2 expression was not significantly higher in rosacea tissues than in normal skin tissues. A positive correlation between PAR-2 and cathelicidin within rosacea samples was observed (R=0.330, p=0.037). After treatment of PAR-2 AP, both mRNA and protein levels for PAR-2, cathelicidin, and VEGF significantly increased in cultured keratinocytes, compared with PAR-2 control peptide treatment. Conclusion PAR-2 may participate in the pathogenesis of rosacea through activation of cathelicidin LL-37, a mediator of innate immune responses in the skin. PMID:25323904

Involvement of proteinase activated receptor-2 in the vascular response to sphingosine 1-phosphate.

PubMed

Roviezzo, Fiorentina; De Angelis, Antonella; De Gruttola, Luana; Bertolino, Antonio; Sullo, Nikol; Brancaleone, Vincenzo; Bucci, Mariarosaria; De Palma, Raffaele; Urbanek, Konrad; D'Agostino, Bruno; Ianaro, Angela; Sorrentino, Raffaella; Cirino, Giuseppe

2014-04-01

S1P (sphingosine 1-phosphate) represents one of the key latest additions to the list of vasoactive substances that modulate vascular tone. PAR-2 (proteinase activated receptor-2) has been shown to be involved in cardiovascular function. In the present study, we investigated the involvement of PAR-2 in S1P-induced effect on vascular tone. The present study has been performed by using isolated mouse aortas. Both S1P and PAR-2 agonists induced endothelium-dependent vasorelaxation. L-NAME (N(G)-nitro-L-arginine methyl ester) and wortmannin abrogated the S1P-induced vasorelaxatioin, while significantly inhibiting the PAR-2-mediated effect. Either ENMD1068, a PAR-2 antagonist, or gabexate, a serine protease inhibitor, significantly inhibited S1P-induced vasorelaxation. Aortic tissues harvested from mice overexpressing PAR-2 displayed a significant increase in vascular response to S1P as opposed to PAR-2-null mice. Immunoprecipitation and immunofluorescence studies demonstrated that S1P(1) interacted with PAR-2 and co-localized with PAR-2 on the vascular endothelial surface. Furthermore, S1P administration to vascular tissues triggered PAR-2 mobilization from the plasma membrane to the perinuclear area; S1P-induced translocation of PAR-2 was abrogated when aortic rings were pre-treated with ENMD1068 or when caveolae dysfunction occurred. Similarly, experiments performed in cultured endothelial cells (human umbilical vein endothelial cells) showed a co-localization of S1P(1) and PAR2, as well as the ability of S1P to induce PAR-2 trafficking. Our results suggest that S1P induces endothelium-dependent vasorelaxation mainly through S1P(1) and involves PAR-2 transactivation.

Expression of Par3 polarity protein correlates with poor prognosis in ovarian cancer.

PubMed

Nakamura, Hiroe; Nagasaka, Kazunori; Kawana, Kei; Taguchi, Ayumi; Uehara, Yuriko; Yoshida, Mitsuyo; Sato, Masakazu; Nishida, Haruka; Fujimoto, Asaha; Inoue, Tomoko; Adachi, Katsuyuki; Nagamatsu, Takeshi; Arimoto, Takahide; Oda, Katsutoshi; Osuga, Yutaka; Fujii, Tomoyuki

2016-11-17

Previous studies have shown that the cell polarity protein partitioning defective 3 (Par3) plays an essential role in the formation of tight junctions and definition of apical-basal polarity. Aberrant function of this protein has been reported to be involved in epithelial-mesenchymal transition (EMT) and cancer invasion. The aim of this study was to examine the functional mechanism of Par3 in ovarian cancer. First, we investigated the association between Par3 expression level and survival of 50 ovarian cancer patients. Next, we conducted an in vitro analysis of ovarian cancer cell lines, focusing on the cell line JHOC5, to investigate Par3 function. To investigate the function of Par3 in invasion, the IL-6/STAT3 pathway was analyzed upon Par3 knockdown with siRNA. The effect of siRNA treatment was assessed by qPCR, ELISA, and western blotting. Invasiveness and cell proliferation following treatment with siRNA against Par3 were investigated using Matrigel chamber, wound healing, and cell proliferation assays. Expression array data for ovarian cancer patient samples revealed low Par3 expression was significantly associated with good prognosis. Univariate analysis of clinicopathological factors revealed significant association between high Par3 levels and peritoneal dissemination at the time of diagnosis. Knockdown of Par3 in JHOC5 cells suppressed cell invasiveness, migration, and cell proliferation with deregulation of IL-6/STAT3 activity. Taken together, these results suggest that Par3 expression is likely involved in ovarian cancer progression, especially in peritoneal metastasis. The underlying mechanism may be that Par3 modulates IL-6 /STAT3 signaling. Here, we propose that the expression of Par3 in ovarian cancer may control disease outcome.

In vitro and in vivo inhibition of proangiogenic retinal phenotype by an antisense oligonucleotide downregulating uPAR expression.

PubMed

Lulli, Matteo; Cammalleri, Maurizio; Granucci, Irene; Witort, Ewa; Bono, Silvia; Di Gesualdo, Federico; Lupia, Antonella; Loffredo, Rosa; Casini, Giovanni; Dal Monte, Massimo; Capaccioli, Sergio

2017-08-26

Neoangiogenesis is the main pathogenic event involved in a variety of retinal diseases. It has been recently demonstrated that inhibiting the urokinase-type plasminogen activator receptor (uPAR) results in reduced angiogenesis in a mouse model of oxygen-induced retinopathy (OIR), establishing uPAR as a therapeutic target in proliferative retinopathies. Here, we evaluated in cultured human retinal endothelial cells (HRECs) and in OIR mice the potential of a specific antisense oligodeoxyribonucleotide (ASO) in blocking the synthesis of uPAR and in providing antiangiogenic effects. uPAR expression in HRECs was inhibited by lipofection with the phosphorotioated 5'-CGGCGGGTGACCCATGTG-3' ASO-uPAR, complementary to the initial translation site of uPAR mRNA. Inhibition of uPAR expression via ASO-uPAR was evaluated in HRECs by analyzing VEGF-induced tube formation and migration. In addition, the well-established and reproducible murine OIR model was used to induce retinal neovascularization in vivo. OIR mice were injected intraperitoneally with ASO-uPAR and retinopathy was evaluated considering the extent of the avascular area in the central retina and neovascular tuft formation. The ASO-uPAR specifically decreased uPAR mRNA and protein levels in HRECs and mitigated VEGF-induced tube formation and cell migration. Noteworthy, in OIR mice ASO-uPAR administration reduced both the avascular area and the formation of neovascular tufts. In conclusion, although the extrapolation of these experimental findings to the clinic is not straightforward, ASO-uPAR may be considered a potential therapeutic tool for treatment of proliferative retinal diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Urokinase receptor expression involves tyrosine phosphorylation of phosphoglycerate kinase.

PubMed

Shetty, Praveenkumar; Velusamy, Thirunavukkarasu; Bhandary, Yashodhar P; Liu, Ming C; Shetty, Sreerama

2010-02-01

The interaction of urokinase-type plasminogen activator (uPA) with its receptor, uPAR, plays a central role in several pathophysiological processes, including cancer. uPA induces its own cell surface receptor expression through stabilization of uPAR mRNA. The mechanism involves binding of a 51 nt uPAR mRNA coding sequence with phosphoglycerate kinase (PGK) to down regulate cell surface uPAR expression. Tyrosine phosphorylation of PGK mediated by uPA treatment enhances uPAR mRNA stabilization. In contrast, inhibition of tyrosine phosphorylation augments PGK binding to uPAR mRNA and attenuates uPA-induced uPAR expression. Mapping the specific peptide region of PGK indicated that its first quarter (amino acids 1-100) interacts with uPAR mRNA. To determine if uPAR expression by uPA is regulated through activation of tyrosine residues of PGK, we mutated the specific tyrosine residue and tested mutant PGK for its ability to interfere with uPAR expression. Inhibition of tyrosine phosphorylation by mutating Y76 residue abolished uPAR expression induced by uPA treatment. These findings collectively demonstrate that Y76 residue present in the first quarter of the PGK molecule is involved in lung epithelial cell surface uPAR expression. This region can effectively mimic the function of a whole PGK molecule in inhibiting tumor cell growth.

A family of ParA-like ATPases promotes cell pole maturation by facilitating polar localization of chemotaxis proteins

PubMed Central

Ringgaard, Simon; Schirner, Kathrin; Davis, Brigid M.; Waldor, Matthew K.

2011-01-01

Stochastic processes are thought to mediate localization of membrane-associated chemotaxis signaling clusters in peritrichous bacteria. Here, we identified a new family of ParA-like ATPases (designated ParC [for partitioning chemotaxis]) encoded within chemotaxis operons of many polar-flagellated γ-proteobacteria that actively promote polar localization of chemotaxis proteins. In Vibrio cholerae, a single ParC focus is found at the flagellated old pole in newborn cells, and later bipolar ParC foci develop as the cell matures. The cell cycle-dependent redistribution of ParC occurs by its release from the old pole and subsequent relocalization at the new pole, consistent with a “diffusion and capture” model for ParC dynamics. Chemotaxis proteins encoded in the same cluster as ParC have a similar unipolar-to-bipolar transition; however, they reach the new pole after the arrival of ParC. Cells lacking ParC exhibit aberrantly localized foci of chemotaxis proteins, reduced chemotaxis, and altered motility, which likely accounts for their enhanced colonization of the proximal small intestine in an animal model of cholera. Collectively, our findings indicate that ParC promotes the efficiency of chemotactic signaling processes. In particular, ParC-facilitated development of a functional chemotaxis apparatus at the new pole readies this site for its development into a functional old pole after cell division. PMID:21764856

Proteinase activated-receptors-associated signaling in the control of gastric cancer

PubMed Central

Sedda, Silvia; Marafini, Irene; Caruso, Roberta; Pallone, Francesco; Monteleone, Giovanni

2014-01-01

Gastric cancer (GC) is the fourth most common cancer in the world and the second cause of cancer-related death. Gastric carcinogenesis is a multifactorial process, in which environmental and genetic factors interact to activate multiple intracellular signals thus leading to uncontrolled growth and survival of GC cells. One such a pathway is regulated by proteinase activated-receptors (PARs), seven transmembrane-spanning domain G protein-coupled receptors, which comprise four receptors (i.e., PAR-1, PAR-2, PAR-3, and PAR-4) activated by various proteases. Both PAR-1 and PAR-2 are over-expressed on GC cells and their activation triggers and/or amplifies intracellular pathways, which sustain gastric carcinogenesis. There is also evidence that expression of either PAR-1 or PAR-2 correlates with depth of wall invasion and metastatic dissemination and inversely with the overall survival of patients. Consistently, data emerging from experimental models of GC suggest that both these receptors can be important targets for therapeutic interventions in GC patients. In contrast, PAR-4 levels are down-regulated in GC and correlate inversely with the aggressiveness of GC, thus suggesting a negative role of this receptor in the control of GC. In this article we review the available data on the expression and role of PARs in GC and discuss whether manipulation of PAR-driven signals may be useful for interfering with GC cell behavior. PMID:25232234

Respiratory motion management using audio-visual biofeedback for respiratory-gated radiotherapy of synchrotron-based pulsed heavy-ion beam delivery

PubMed Central

He, Pengbo; Li, Qiang; Liu, Xinguo; Dai, Zhongying; Zhao, Ting; Fu, Tingyan; Shen, Guosheng; Ma, Yuanyuan; Huang, Qiyan; Yan, Yuanlin

2014-01-01

Purpose: To efficiently deliver respiratory-gated radiation during synchrotron-based pulsed heavy-ion radiotherapy, a novel respiratory guidance method combining a personalized audio-visual biofeedback (BFB) system, breath hold (BH), and synchrotron-based gating was designed to help patients synchronize their respiratory patterns with synchrotron pulses and to overcome typical limitations such as low efficiency, residual motion, and discomfort. Methods: In-house software was developed to acquire body surface marker positions and display BFB, gating signals, and real-time beam profiles on a LED screen. Patients were prompted to perform short BHs or short deep breath holds (SDBH) with the aid of BFB following a personalized standard BH/SDBH (stBH/stSDBH) guiding curve or their own representative BH/SDBH (reBH/reSDBH) guiding curve. A practical simulation was performed for a group of 15 volunteers to evaluate the feasibility and effectiveness of this method. Effective dose rates (EDRs), mean absolute errors between the guiding curves and the measured curves, and mean absolute deviations of the measured curves were obtained within 10%–50% duty cycles (DCs) that were synchronized with the synchrotron’s flat-top phase. Results: All maneuvers for an individual volunteer took approximately half an hour, and no one experienced discomfort during the maneuvers. Using the respiratory guidance methods, the magnitude of residual motion was almost ten times less than during nongated irradiation, and increases in the average effective dose rate by factors of 2.39–4.65, 2.39–4.59, 1.73–3.50, and 1.73–3.55 for the stBH, reBH, stSDBH, and reSDBH guiding maneuvers, respectively, were observed in contrast with conventional free breathing-based gated irradiation, depending on the respiratory-gated duty cycle settings. Conclusions: The proposed respiratory guidance method with personalized BFB was confirmed to be feasible in a group of volunteers. Increased effective dose rate and improved overall treatment precision were observed compared to conventional free breathing-based, respiratory-gated irradiation. Because breathing guidance curves could be established based on the respective average respiratory period and amplitude for each patient, it may be easier for patients to cooperate using this technique. PMID:25370622

Respiratory motion management using audio-visual biofeedback for respiratory-gated radiotherapy of synchrotron-based pulsed heavy-ion beam delivery

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

He, Pengbo; Ma, Yuanyuan; Huang, Qiyan

Purpose: To efficiently deliver respiratory-gated radiation during synchrotron-based pulsed heavy-ion radiotherapy, a novel respiratory guidance method combining a personalized audio-visual biofeedback (BFB) system, breath hold (BH), and synchrotron-based gating was designed to help patients synchronize their respiratory patterns with synchrotron pulses and to overcome typical limitations such as low efficiency, residual motion, and discomfort. Methods: In-house software was developed to acquire body surface marker positions and display BFB, gating signals, and real-time beam profiles on a LED screen. Patients were prompted to perform short BHs or short deep breath holds (SDBH) with the aid of BFB following a personalized standardmore » BH/SDBH (stBH/stSDBH) guiding curve or their own representative BH/SDBH (reBH/reSDBH) guiding curve. A practical simulation was performed for a group of 15 volunteers to evaluate the feasibility and effectiveness of this method. Effective dose rates (EDRs), mean absolute errors between the guiding curves and the measured curves, and mean absolute deviations of the measured curves were obtained within 10%–50% duty cycles (DCs) that were synchronized with the synchrotron’s flat-top phase. Results: All maneuvers for an individual volunteer took approximately half an hour, and no one experienced discomfort during the maneuvers. Using the respiratory guidance methods, the magnitude of residual motion was almost ten times less than during nongated irradiation, and increases in the average effective dose rate by factors of 2.39–4.65, 2.39–4.59, 1.73–3.50, and 1.73–3.55 for the stBH, reBH, stSDBH, and reSDBH guiding maneuvers, respectively, were observed in contrast with conventional free breathing-based gated irradiation, depending on the respiratory-gated duty cycle settings. Conclusions: The proposed respiratory guidance method with personalized BFB was confirmed to be feasible in a group of volunteers. Increased effective dose rate and improved overall treatment precision were observed compared to conventional free breathing-based, respiratory-gated irradiation. Because breathing guidance curves could be established based on the respective average respiratory period and amplitude for each patient, it may be easier for patients to cooperate using this technique.« less

PAR-2 mediates increased inflammatory cell adhesion and neointima formation following vascular injury in the mouse.

PubMed

Tennant, Gail M; Wadsworth, Roger M; Kennedy, Simon

2008-05-01

Activation of PAR-2 in the vasculature affects vascular tone and adhesion of leukocytes to the endothelium. Since adhesion of leukocytes is increased following vascular injury and is important in determining the extent of neointima formation, we hypothesised that mice lacking PAR-2 may have reduced neointima formation following vascular injury. PAR-2 activating peptides and trypsin induced endothelium-dependent relaxation of mouse carotid artery which was absent in the knockout mouse. Lack of a PAR-2 receptor did not affect lymphocyte adhesion under basal conditions, but reduced the contractile response produced by lymphocytes. Twenty-eight days after denuding injury, vessel contraction to lymphocytes was reduced in both strains while lymphocyte adhesion was significantly greater in PAR-2(+/+) mice compared to the PAR-2 knockout mice. Neointimal area was markedly reduced in the PAR-2 knockout mouse. Our data show that PAR-2 modulates inflammatory cell adhesion when stimulated and in mice lacking the PAR-2 receptor, adhesion to injured vessels is reduced with a consequent reduction in neointima formation.

The polarity protein Par3 regulates APP trafficking and processing through the endocytic adaptor protein Numb.

PubMed

Sun, Miao; Asghar, Suwaiba Z; Zhang, Huaye

2016-09-01

The processing of amyloid precursor protein (APP) into β-amyloid peptide (Aβ) is a key step in the pathogenesis of Alzheimer's disease (AD), and trafficking dysregulations of APP and its secretases contribute significantly to altered APP processing. Here we show that the cell polarity protein Par3 plays an important role in APP processing and trafficking. We found that the expression of full length Par3 is significantly decreased in AD patients. Overexpression of Par3 promotes non-amyloidogenic APP processing, while depletion of Par3 induces intracellular accumulation of Aβ. We further show that Par3 functions by regulating APP trafficking. Loss of Par3 decreases surface expression of APP by targeting APP to the late endosome/lysosome pathway. Finally, we show that the effects of Par3 are mediated through the endocytic adaptor protein Numb, and Par3 functions by interfering with the interaction between Numb and APP. Together, our studies show a novel role for Par3 in regulating APP processing and trafficking. Copyright © 2016 Elsevier Inc. All rights reserved.

The procedure execution manager and its application to Advanced Photon Source operation

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

Borland, M.

1997-06-01

The Procedure Execution Manager (PEM) combines a complete scripting environment for coding accelerator operation procedures with a manager application for executing and monitoring the procedures. PEM is based on Tcl/Tk, a supporting widget library, and the dp-tcl extension for distributed processing. The scripting environment provides support for distributed, parallel execution of procedures along with join and abort operations. Nesting of procedures is supported, permitting the same code to run as a top-level procedure under operator control or as a subroutine under control of another procedure. The manager application allows an operator to execute one or more procedures in automatic, semi-automatic,more » or manual modes. It also provides a standard way for operators to interact with procedures. A number of successful applications of PEM to accelerator operations have been made to date. These include start-up, shutdown, and other control of the positron accumulator ring (PAR), low-energy transport (LET) lines, and the booster rf systems. The PAR/LET procedures make nested use of PEM`s ability to run parallel procedures. There are also a number of procedures to guide and assist tune-up operations, to make accelerator physics measurements, and to diagnose equipment. Because of the success of the existing procedures, expanded use of PEM is planned.« less

Heat shock proteins HSP70 and MRJ cooperatively regulate cell adhesion and migration through urokinase receptor.

PubMed

Lin, Yuli; Peng, Nana; Zhuang, Hongqin; Zhang, Di; Wang, Yao; Hua, Zi-Chun

2014-08-30

The urokinase-type plasminogen activator receptor (uPAR) is an important regulator of ECM proteolysis, cell-ECM interactions and cell signaling. uPAR and heat shock proteins HSP70 and MRJ (DNAJB6) have been implicated in tumor growth and metastasis. We have reported recently that MRJ (DNAJB6, a heat shock protein) can interact with uPAR and enhance cell adhesion. Here, we identified another heat shock protein HSP70 as a novel uPAR-interacting protein. We performed co-immunoprecipitation in human embryonic kidney (HEK) 293 and colon cancer HCT116 cells as well as immunofluorence assays in HEK293 cells stably transfected with uPAR to investigate the association of suPAR with HSP70/MRJ. To understand the biological functions of the triple complex of suPAR/HSP70/MRJ, we determined whether HSP70 and/or MRJ regulated uPAR-mediated cell invasion, migration, adhesion to vitronectin and MAPK pathway in two pair of human tumor cells (uPAR negative HEK293 cells vs HEK293 cells stably transfected with uPAR and HCT116 cells stably transfected with antisense-uPAR vs HCT116 mock cells transfected with vector only) using transwell assay, wound healing assay, quantitative RT-PCR analyzing mmp2 and mmp9 transcription levels, cell adhesion assay and Western blotting assay. HSP70 and MRJ formed a triple complex with uPAR and over-expression of MRJ enhanced the interaction between HSP70 and uPAR, while knockdown of MRJ decreased soluble uPAR in HCT116 cells (P < 0.05) and reduced the formation of the triple complex, suggesting that MRJ may act as an uPAR-specific adaptor protein to link uPAR to HSP70. Further experiments showed that knockdown of HSP70 and/or MRJ by siRNA inhibited uPAR-mediated cell adhesion to vitronectin as well as suppressed cell invasion and migration. Knockdown of HSP70 and/or MRJ inhibited expression of invasion related genes mmp2 and mmp9. Finally, HSP70 and/or MRJ up-regulated phosphorylation levels of ERK1/2 and FAK suggesting MAPK pathway was involved. All the biological function experiments in cell level showed an additive effect when HSP70 and MRJ were regulated simultaneously indicating their collaborated regulation effects on uPAR. These findings may offer a novel insight into the interactions between uPAR and HSP70/MRJ and their functions in cell adhesion and migration may provide more understanding of the roles in regulating cancer metastasis.

Impact of MR-guided boiling histotripsy in distinct murine tumor models.

PubMed

Hoogenboom, Martijn; Eikelenboom, Dylan C; van den Bijgaart, Renske J E; Heerschap, Arend; Wesseling, Pieter; den Brok, Martijn H; Fütterer, Jurgen J; Adema, Gosse J

2017-09-01

Interest in mechanical high intensity focused ultrasound (HIFU) ablation is rapidly growing. Boiling histotripsy (BH) is applied for mechanical fragmentation of soft tissue into submicron fragments with limited temperature increase using the shock wave and cavitation effects of HIFU. Research on BH has been largely limited to ex vivo experiments. As a consequence, the in vivo pathology after BH treatment and the relation to preexistent tissue characteristics are not well understood. This study reports on in vivo MR guided BH treatment, either with 100 or 200 pulses per focal spot, in three different subcutaneous mouse tumor models: a soft-tissue melanoma (B16OVA), a compact growing thymoma (EL4), and a highly vascularized neuroblastoma (9464D). Extensive treatment evaluation was performed using MR imaging followed by histopathology 2h after treatment. T2 weighted MRI allowed direct in vivo visualization of the BH lesions in all tumor models. The 100-pulse treated area in the B16OVA tumors was larger than the predicted treatment volume (500±10%). For the more compact growing EL4 and 9464D tumors this was 95±13% and 55±33%, respectively. Histopathology after the 100-pulse treatment revealed completely disintegrated lesions in the treated area with sharp borders in the compact EL4 and 9464D tumors, while for B16OVA tumors the lesion contained a mixture of discohesive (partly viable) clusters of cells, micro-vessel remainings, and tumor cell debris. The treatment of B16OVA with 200 pulses increased the fragmentation of tumor tissue. In all tumor types only micro-hemorrhages were detected after ablation (slightly higher after 200-pulse treatment for the highly vascularized 9464D tumors). Collagen staining revealed that the collagen fibers were to a greater or lesser extent still intact and partly clotted together near the lesion border in all tumor models. In conclusion, this study reveals effective mechanical fragmentation of different tumor types using BH without major hemorrhages. However, treatment settings may need to be adjusted to the tissue characteristics for optimal tissue fragmentation. Copyright © 2017 Elsevier B.V. All rights reserved.

Acoustic Guided Wave Testing of Pipes of Small Diameters

NASA Astrophysics Data System (ADS)

Muravev, V. V.; Muraveva, O. V.; Strizhak, V. A.; Myshkin, Y. V.

2017-10-01

Acoustic path is analyzed and main parameters of guided wave testing are substanti- ated applied to pipes of small diameters. The method is implemented using longitudinal L(0,1) and torsional T(0,1) waves based on electromagnetic-acoustic (EMA) transducers. The method of multiple reflections (MMR) combines echo-through, amplitude-shadow and time-shadow methods. Due to the effect of coherent amplification of echo-pulses from defects the sensitivity to the defects of small sizes at the signal analysis on the far reflections is increased. An oppor- tunity of detection of both local defects (dents, corrosion damages, rolling features, pitting, cracks) and defects extended along the pipe is shown.

Theory and Simulation of Gain-Guided Noncollinear Modes in Chirped Quasi-Phase-Matched Optical Parametric Amplifiers

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

Charbonneau-Lefort, Mathieu; Afeyan, Bedros; Fejer, Martin

Chirped quasi-phase-matched (QPM) gratings offer essentially constant gain over wide bandwidths, making them promising candidates for short-pulse optical parametric amplifiers. However, experiments have shown that high-gain non-collinear processes exist in spite of the dephasing caused by the non-uniformity of the QPM grating and compete with the desired collinear broadband gain of the amplifier. In this paper, these non-collinear gain-guided modes are investigated numerically and analytically in a model that includes longitudinal non-uniformity of the phase-matching profile, lateral localization of the pump beam and non-collinear propagation of the interacting waves.

Superradiance for Atoms Trapped along a Photonic Crystal Waveguide

NASA Astrophysics Data System (ADS)

Goban, A.; Hung, C.-L.; Hood, J. D.; Yu, S.-P.; Muniz, J. A.; Painter, O.; Kimble, H. J.

2015-08-01

We report observations of superradiance for atoms trapped in the near field of a photonic crystal waveguide (PCW). By fabricating the PCW with a band edge near the D1 transition of atomic cesium, strong interaction is achieved between trapped atoms and guided-mode photons. Following short-pulse excitation, we record the decay of guided-mode emission and find a superradiant emission rate scaling as Γ¯SR∝N ¯Γ1 D for average atom number 0.19 ≲N ¯≲2.6 atoms, where Γ1 D/Γ'=1.0 ±0.1 is the peak single-atom radiative decay rate into the PCW guided mode, and Γ' is the radiative decay rate into all the other channels. These advances provide new tools for investigations of photon-mediated atom-atom interactions in the many-body regime.

Focused US system for MR imaging-guided tumor ablation.

PubMed

Cline, H E; Hynynen, K; Watkins, R D; Adams, W J; Schenck, J F; Ettinger, R H; Freund, W R; Vetro, J P; Jolesz, F A

1995-03-01

To measure the performance characteristics of a focused ultrasound (US) system for magnetic resonance (MR) imaging-guided tumor ablation. The authors constructed a focused US system for MR imaging-guided tumor ablation. The location of the heated region and thermal dose were monitored with temperature-sensitive MR images obtained in phantoms and rabbit skeletal muscle after application of each sonic pulse. The region heated by the focused ultrasound beam was within 1 mm of that observed on temperature-sensitive fast gradient-echo MR images of in vivo rabbit skeletal muscle. Analysis of heat flow and the rate of coagulation necrosis provided an estimate of the size of the ablated region that was in agreement with experimental findings. MR imaging provides target definition and control for thermal therapy in regions of variable perfusion or in tissues that are not well characterized.

Proteinase-activated receptor 2 modulates OA-related pain, cartilage and bone pathology.

PubMed

Huesa, Carmen; Ortiz, Ana C; Dunning, Lynette; McGavin, Laura; Bennett, Louise; McIntosh, Kathryn; Crilly, Anne; Kurowska-Stolarska, Mariola; Plevin, Robin; van 't Hof, Rob J; Rowan, Andrew D; McInnes, Iain B; Goodyear, Carl S; Lockhart, John C; Ferrell, William R

2016-11-01

Proteinase-activated receptor 2 (PAR2) deficiency protects against cartilage degradation in experimental osteoarthritis (OA). The wider impact of this pathway upon OA-associated pathologies such as osteophyte formation and pain is unknown. Herein, we investigated early temporal bone and cartilage changes in experimental OA in order to further elucidate the role of PAR2 in OA pathogenesis. OA was induced in wild-type (WT) and PAR2-deficient (PAR2 -/- ) mice by destabilisation of the medial meniscus (DMM). Inflammation, cartilage degradation and bone changes were monitored using histology and microCT. In gene rescue experiments, PAR2 -/- mice were intra-articularly injected with human PAR2 (hPAR2)-expressing adenovirus. Dynamic weight bearing was used as a surrogate of OA-related pain. Osteophytes formed within 7 days post-DMM in WT mice but osteosclerosis was only evident from 14 days post induction. Importantly, PAR2 was expressed in the proliferative/hypertrophic chondrocytes present within osteophytes. In PAR2 -/- mice, osteophytes developed significantly less frequently but, when present, were smaller and of greater density; no osteosclerosis was observed in these mice up to day 28. The pattern of weight bearing was altered in PAR2 -/- mice, suggesting reduced pain perception. The expression of hPAR2 in PAR2 -/- mice recapitulated osteophyte formation and cartilage damage similar to that observed in WT mice. However, osteosclerosis was absent, consistent with lack of hPAR2 expression in subchondral bone. This study clearly demonstrates PAR2 plays a critical role, via chondrocytes, in osteophyte development and subchondral bone changes, which occur prior to PAR2-mediated cartilage damage. The latter likely occurs independently of OA-related bone changes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

RF Pulse Design using Nonlinear Gradient Magnetic Fields

PubMed Central

Kopanoglu, Emre; Constable, R. Todd

2014-01-01

Purpose An iterative k-space trajectory and radio-frequency (RF) pulse design method is proposed for Excitation using Nonlinear Gradient Magnetic fields (ENiGMa). Theory and Methods The spatial encoding functions (SEFs) generated by nonlinear gradient fields (NLGFs) are linearly dependent in Cartesian-coordinates. Left uncorrected, this may lead to flip-angle variations in excitation profiles. In the proposed method, SEFs (k-space samples) are selected using a Matching-Pursuit algorithm, and the RF pulse is designed using a Conjugate-Gradient algorithm. Three variants of the proposed approach are given: the full-algorithm, a computationally-cheaper version, and a third version for designing spoke-based trajectories. The method is demonstrated for various target excitation profiles using simulations and phantom experiments. Results The method is compared to other iterative (Matching-Pursuit and Conjugate Gradient) and non-iterative (coordinate-transformation and Jacobian-based) pulse design methods as well as uniform density spiral and EPI trajectories. The results show that the proposed method can increase excitation fidelity significantly. Conclusion An iterative method for designing k-space trajectories and RF pulses using nonlinear gradient fields is proposed. The method can either be used for selecting the SEFs individually to guide trajectory design, or can be adapted to design and optimize specific trajectories of interest. PMID:25203286

Proteolytic Activation of the Protease-activated Receptor (PAR)-2 by the Glycosylphosphatidylinositol-anchored Serine Protease Testisin*

PubMed Central

Driesbaugh, Kathryn H.; Buzza, Marguerite S.; Martin, Erik W.; Conway, Gregory D.; Kao, Joseph P. Y.; Antalis, Toni M.

2015-01-01

Protease-activated receptors (PARs) are a family of seven-transmembrane, G-protein-coupled receptors that are activated by multiple serine proteases through specific N-terminal proteolytic cleavage and the unmasking of a tethered ligand. The majority of PAR-activating proteases described to date are soluble proteases that are active during injury, coagulation, and inflammation. Less investigation, however, has focused on the potential for membrane-anchored serine proteases to regulate PAR activation. Testisin is a unique trypsin-like serine protease that is tethered to the extracellular membrane of cells through a glycophosphatidylinositol (GPI) anchor. Here, we show that the N-terminal domain of PAR-2 is a substrate for testisin and that proteolytic cleavage of PAR-2 by recombinant testisin activates downstream signaling pathways, including intracellular Ca2+ mobilization and ERK1/2 phosphorylation. When testisin and PAR-2 are co-expressed in HeLa cells, GPI-anchored testisin specifically releases the PAR-2 tethered ligand. Conversely, knockdown of endogenous testisin in NCI/ADR-Res ovarian tumor cells reduces PAR-2 N-terminal proteolytic cleavage. The cleavage of PAR-2 by testisin induces activation of the intracellular serum-response element and NFκB signaling pathways and the induction of IL-8 and IL-6 cytokine gene expression. Furthermore, the activation of PAR-2 by testisin results in the loss and internalization of PAR-2 from the cell surface. This study reveals a new biological substrate for testisin and is the first demonstration of the activation of a PAR by a serine protease GPI-linked to the cell surface. PMID:25519908

Par3L enhances colorectal cancer cell survival by inhibiting Lkb1/AMPK signaling pathway

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

Li, Taiyuan; Liu, Dongning; Lei, Xiong

Partitioning defective 3-like protein (Par3L) is a recently identified cell polarity protein that plays an important role in mammary stem cell maintenance. Previously, we showed that high expression of Par3L is associated with poor survival in malignant colorectal cancer (CRC), but the underlying mechanism remained unknown. To this end, we established a Par3L knockout colorectal cancer cell line using the CRISPR/Cas system. Interestingly, reduced proliferation, enhanced cell death and caspase-3 activation were observed in Par3L knockout (KO) cells as compared with wildtype (WT) cells. Consistent with previous studies, we showed that Par3L interacts with a tumor suppressor protein liver kinasemore » B1 (Lkb1). Moreover, Par3L depletion resulted in abnormal activation of Lkb1/AMPK signaling cascade. Knockdown of Lkb1 in these cells could significantly reduce AMPK activity and partially rescue cell death caused by Par3L knockdown. Furthermore, we showed that Par3L KO cells were more sensitive to chemotherapies and irradiation. Together, these results suggest that Par3L is essential for colorectal cancer cell survival by inhibiting Lkb1/AMPK signaling pathway, and is a putative therapeutic target for CRC. - Highlights: • Par3L knockout using the CRISPR/Cas system induces apoptosis in colorectal cancer cells. • Par3L interacts with Lkb1 and regulates the activity of AMPK signaling cascade. • Par3L knockout cells are more sensitive to treatment of different chemotherapy drugs and irradiation.« less

How to use saturation monitoring in newborns.

PubMed

McVea, Steven; McGowan, Michael; Rao, Bharathi

2018-05-10

Pulse oximetry is a first-line monitoring tool, used in neonatal medicine routinely as a part of continuous monitoring during intensive care. It is also used to guide response to resuscitation and as a screening tool for congenital heart disease. Despite its widespread use, many healthcare providers are unaware of the underlying principles and limitations of pulse oximetry in neonates. In this article, we will discuss the physiological and technological principles behind the use of saturation monitoring and its use in neonatal practice. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A three-dimensional ParF meshwork assembles through the nucleoid to mediate plasmid segregation.

PubMed

McLeod, Brett N; Allison-Gamble, Gina E; Barge, Madhuri T; Tonthat, Nam K; Schumacher, Maria A; Hayes, Finbarr; Barillà, Daniela

2017-04-07

Genome segregation is a fundamental step in the life cycle of every cell. Most bacteria rely on dedicated DNA partition proteins to actively segregate chromosomes and low copy-number plasmids. Here, by employing super resolution microscopy, we establish that the ParF DNA partition protein of the ParA family assembles into a three-dimensional meshwork that uses the nucleoid as a scaffold and periodically shuttles between its poles. Whereas ParF specifies the territory for plasmid trafficking, the ParG partner protein dictates the tempo of ParF assembly cycles and plasmid segregation events by stimulating ParF adenosine triphosphate hydrolysis. Mutants in which this ParG temporal regulation is ablated show partition deficient phenotypes as a result of either altered ParF structure or dynamics and indicate that ParF nucleoid localization and dynamic relocation, although necessary, are not sufficient per se to ensure plasmid segregation. We propose a Venus flytrap model that merges the concepts of ParA polymerization and gradient formation and speculate that a transient, dynamic network of intersecting polymers that branches into the nucleoid interior is a widespread mechanism to distribute sizeable cargos within prokaryotic cells. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Bacterial DNA segregation dynamics mediated by the polymerizing protein ParF.

PubMed

Barillà, Daniela; Rosenberg, Mark F; Nobbmann, Ulf; Hayes, Finbarr

2005-04-06

Prokaryotic DNA segregation most commonly involves members of the Walker-type ParA superfamily. Here we show that the ParF partition protein specified by the TP228 plasmid is a ParA ATPase that assembles into extensive filaments in vitro. Polymerization is potentiated by ATP binding and does not require nucleotide hydrolysis. Analysis of mutations in conserved residues of the Walker A motif established a functional coupling between filament dynamics and DNA partitioning. The partner partition protein ParG plays two separable roles in the ParF polymerization process. ParF is unrelated to prokaryotic polymerizing proteins of the actin or tubulin families, but is a homologue of the MinD cell division protein, which also assembles into filaments. The ultrastructures of the ParF and MinD polymers are remarkably similar. This points to an evolutionary parallel between DNA segregation and cytokinesis in prokaryotic cells, and reveals a potential molecular mechanism for plasmid and chromosome segregation mediated by the ubiquitous ParA-type proteins.

Bacterial DNA segregation dynamics mediated by the polymerizing protein ParF

PubMed Central

Barillà, Daniela; Rosenberg, Mark F; Nobbmann, Ulf; Hayes, Finbarr

2005-01-01

Prokaryotic DNA segregation most commonly involves members of the Walker-type ParA superfamily. Here we show that the ParF partition protein specified by the TP228 plasmid is a ParA ATPase that assembles into extensive filaments in vitro. Polymerization is potentiated by ATP binding and does not require nucleotide hydrolysis. Analysis of mutations in conserved residues of the Walker A motif established a functional coupling between filament dynamics and DNA partitioning. The partner partition protein ParG plays two separable roles in the ParF polymerization process. ParF is unrelated to prokaryotic polymerizing proteins of the actin or tubulin families, but is a homologue of the MinD cell division protein, which also assembles into filaments. The ultrastructures of the ParF and MinD polymers are remarkably similar. This points to an evolutionary parallel between DNA segregation and cytokinesis in prokaryotic cells, and reveals a potential molecular mechanism for plasmid and chromosome segregation mediated by the ubiquitous ParA-type proteins. PMID:15775965

Evidence that compatibility of closely related replicons in Clostridium perfringens depends on linkage to parMRC-like partitioning systems of different subfamilies.

PubMed

Watts, Thomas D; Johanesen, Priscilla A; Lyras, Dena; Rood, Julian I; Adams, Vicki

2017-05-01

Clostridium perfringens produces an extensive repertoire of toxins and extracellular enzymes, many of which are intimately involved in the progression of disease and are encoded by genes on conjugative plasmids. In addition, many C. perfringens strains can carry up to five of these conjugative toxin or antimicrobial resistance plasmids, each of which has a similar 35kb backbone. This conserved backbone includes the tcp conjugation locus and the central control region (CCR), which encodes genes involved in plasmid regulation, replication and partitioning, including a parMRC partitioning locus. Most conjugative plasmids in C. perfringens have a conserved replication protein, raising questions as to how multiple, closely related plasmids are maintained within a single strain. Bioinformatics analysis has highlighted the presence of at least 10 different parMRC partitioning system families (parMRC A-J ) in these plasmids, with differences in amino acid sequence identity between each ParM family ranging from 15% to 54%. No two plasmids that encode genes belonging to the same partitioning family have been observed in a single strain, suggesting that these families represent the basis for plasmid incompatibility. In an attempt to validate the proposed parMRC incompatibility groups, genetically marked C. perfringens plasmids encoding identical parMRC C or parMRC D homologues or different combinations of parMRC A , parMRC C and parMRC D family homologues were introduced into a single strain via conjugation. The stability of each plasmid was determined using an incompatibility assay in which the plasmid profile of each strain was monitored over the course of two days in the absence of direct selection. The results showed that plasmids with identical parMRC C or parMRC D homologues were incompatible and could not coexist in the absence of external selection. By contrast, plasmids that encoded different parMRC homologues were compatible and could coexist in the same cell in the absence of selection, with the exception of strains housing parMRC C and parMRC D combinations, which showed a minor incompatibility phenotype. In conclusion, we have provided the first direct evidence of plasmid incompatibility in Clostridium spp. and have shown experimentally that the compatibility of conjugative C. perfringens plasmids correlates with the presence of parMRC-like partitioning systems of different phylogenetic subfamilies. Copyright © 2017 Elsevier Inc. All rights reserved.

An Implementation in Pascal: Translation of Prolog into Pascal.

DTIC Science & Technology

1985-06-01

for i:=1 to px do begin ifr (proc .i..relativity=O) then continue; if proc .. ) .ptype=6) hen continue;if (proc (...abegin<>O) then continue; passname...forj:=reitorn do if (j0) then continue; if (par (.>) ppe <>1) then continue; if (par .. .namie<>par(.i.).name) parle nO ype:par C.’ ntype; par Inblnd

ParC subunit of DNA topoisomerase IV of Streptococcus pneumoniae is a primary target of fluoroquinolones and cooperates with DNA gyrase A subunit in forming resistance phenotype.

PubMed Central

Muñoz, R; De La Campa, A G

1996-01-01

The genes encoding the ParC and ParE subunits of topoisomerase IV of Streptococcus pneumoniae, together with the region encoding amino acids 46 to 172 (residue numbers are as in Escherichia coli) of the pneumococcal GyrA subunit, were partially characterized. The gyrA gene maps to a physical location distant from the gyrB and parC loci on the chromosome, whereas parC is closely linked to parE. Ciprofloxacin-resistant (Cpr) clinical isolates of S. pneumoniae had mutations affecting amino acid residues of the quinolone resistance-determining region of ParC (low-level Cpr) or in both quinolone resistance-determining regions of ParC and GyrA (high-level Cpr). Mutations were found in residue positions equivalent to the serine at position 83 and the aspartic acid at position 87 of the E. coli GyrA subunit. Transformation experiments suggest that ParC is the primary target of ciprofloxacin. Mutation in parC appears to be a prerequisite before mutations in gyrA can influence resistance levels. PMID:8891124

Condensin promotes the juxtaposition of DNA flanking its loading site in Bacillus subtilis

PubMed Central

Wang, Xindan; Le, Tung B.K.; Lajoie, Bryan R.; Dekker, Job; Laub, Michael T.; Rudner, David Z.

2015-01-01

SMC condensin complexes play a central role in compacting and resolving replicated chromosomes in virtually all organisms, yet how they accomplish this remains elusive. In Bacillus subtilis, condensin is loaded at centromeric parS sites, where it encircles DNA and individualizes newly replicated origins. Using chromosome conformation capture and cytological assays, we show that condensin recruitment to origin-proximal parS sites is required for the juxtaposition of the two chromosome arms. Recruitment to ectopic parS sites promotes alignment of large tracks of DNA flanking these sites. Importantly, insertion of parS sites on opposing arms indicates that these “zip-up” interactions only occur between adjacent DNA segments. Collectively, our data suggest that condensin resolves replicated origins by promoting the juxtaposition of DNA flanking parS sites, drawing sister origins in on themselves and away from each other. These results are consistent with a model in which condensin encircles the DNA flanking its loading site and then slides down, tethering the two arms together. Lengthwise condensation via loop extrusion could provide a generalizable mechanism by which condensin complexes act dynamically to individualize origins in B. subtilis and, when loaded along eukaryotic chromosomes, resolve them during mitosis. PMID:26253537

PAR-2-mediated control of barrier function and motility differs between early and late phases of postinfectious gut dysfunction in the rat.

PubMed

Fernández-Blanco, Joan Antoni; Fernández-Blanco, Juan A; Hollenberg, Morley D; Martínez, Vicente; Vergara, Patri

2013-02-15

Proteinase-activated receptor-2 (PAR-2) and mast cell (MC) mediators contribute to inflammatory and functional gastrointestinal disorders. We aimed to characterize jejunal PAR-2-mediated responses and the potential MC involvement in the early and late phases of a rat model of postinfectious gut dysfunction. Jejunal tissues of control and Trichinella spiralis-infected (14 and 30 days postinfection) rats, treated or not with the MC stabilizer, ketotifen, were used. Histopathology and immunostaining were used to characterize inflammation, PAR-2 expression, and mucosal and connective tissue MCs. Epithelial barrier function (hydroelectrolytic transport and permeability) and motility were assessed in vitro in basal conditions and after PAR-2 activation. Intestinal inflammation on day 14 postinfection (early phase) was significantly resolved by day 30 (late phase) although MC counts and epithelial permeability remained increased. PAR-2-mediated ion transport (Ussing chambers, in vitro) and epithelial surface PAR-2 expression were reduced in the early phase, with a trend toward normalization during the late phase. In control conditions, PAR-2 activation (organ bath) induced biphasic motor responses (relaxation followed by excitation). At 14 days postinfection, spontaneous contractility and PAR-2-mediated relaxations were enhanced; motor responses were normalized on day 30. Postinfectious changes in PAR-2 functions were not affected by ketotifen treatment. We concluded that, in the rat model of Trichinella spiralis infection, alterations of intestinal PAR-2 function and expression depend on the inflammatory phase considered. A lack of a ketotifen effect suggests no interplay between MCs and PAR-2-mediated motility and ion transport alterations. These observations question the role of MC mediators in PAR-2-modulating postinfectious gut dysfunction.

Proteolytic activation of the protease-activated receptor (PAR)-2 by the glycosylphosphatidylinositol-anchored serine protease testisin.

PubMed

Driesbaugh, Kathryn H; Buzza, Marguerite S; Martin, Erik W; Conway, Gregory D; Kao, Joseph P Y; Antalis, Toni M

2015-02-06

Protease-activated receptors (PARs) are a family of seven-transmembrane, G-protein-coupled receptors that are activated by multiple serine proteases through specific N-terminal proteolytic cleavage and the unmasking of a tethered ligand. The majority of PAR-activating proteases described to date are soluble proteases that are active during injury, coagulation, and inflammation. Less investigation, however, has focused on the potential for membrane-anchored serine proteases to regulate PAR activation. Testisin is a unique trypsin-like serine protease that is tethered to the extracellular membrane of cells through a glycophosphatidylinositol (GPI) anchor. Here, we show that the N-terminal domain of PAR-2 is a substrate for testisin and that proteolytic cleavage of PAR-2 by recombinant testisin activates downstream signaling pathways, including intracellular Ca(2+) mobilization and ERK1/2 phosphorylation. When testisin and PAR-2 are co-expressed in HeLa cells, GPI-anchored testisin specifically releases the PAR-2 tethered ligand. Conversely, knockdown of endogenous testisin in NCI/ADR-Res ovarian tumor cells reduces PAR-2 N-terminal proteolytic cleavage. The cleavage of PAR-2 by testisin induces activation of the intracellular serum-response element and NFκB signaling pathways and the induction of IL-8 and IL-6 cytokine gene expression. Furthermore, the activation of PAR-2 by testisin results in the loss and internalization of PAR-2 from the cell surface. This study reveals a new biological substrate for testisin and is the first demonstration of the activation of a PAR by a serine protease GPI-linked to the cell surface. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Protease-activated receptor 2 in dorsal root ganglion contributes to peripheral sensitization of bone cancer pain.

PubMed

Liu, S; Liu, Y-P; Yue, D-M; Liu, G-J

2014-03-01

Treating bone cancer pain continues to be a major clinical challenge, and the underlying mechanisms of bone cancer pain remain elusive. Protease-activated receptor 2 (PAR2) has been reported to be involved in neurogenic inflammation, nociceptive pain and hyperalgesia. Here, we investigated the role of PAR2 in bone cancer pain development. Expression of PAR2, mechanical allodynia, thermal hyperalgesia and neurochemical alterations induced by bone cancer pain were analysed in male, adult C3H/HeJ mice with tumour cell implantation (TCI). To investigate the contribution of PAR2 to bone cancer pain, PAR2 antagonist peptide and PAR2 knockout mice were used. TCI produced bone cancer-related pain behaviours. Production and persistence of these pain behaviours were well correlated with TCI-induced up-regulation of PAR2 in sciatic nerve and dorsal root ganglia (DRG). PAR2 knockout and spinal administration of PAR2 antagonist peptide prevented and/or reversed bone cancer-related pain behaviours and associated neurochemical changes in DRG and dorsal horn (DH). TCI also induced proteases release in tumour-bearing tibia, sciatic nerve and DRG. Plantar injection of supernatant from sarcoma cells induced PAR2 up-regulation and intracellular calcium [Ca(2+) ]i increase in DRG, and calcitonin gene-related peptide accumulation in DH, as well as significant thermal and mechanical hyperalgesia, which were all in PAR2-dependent manners. These findings suggest that PAR2 may be a key mediator for peripheral sensitization of bone cancer pain. Inhibiting PAR2 activation, especially during the early phase, may be a new therapy for preventing/suppressing development of bone cancer pain. © 2013 European Pain Federation - EFIC®

mTORC2 activation is regulated by the urokinase receptor (uPAR) in bladder cancer.

PubMed

Hau, Andrew M; Leivo, Mariah Z; Gilder, Andrew S; Hu, Jing-Jing; Gonias, Steven L; Hansel, Donna E

2017-01-01

Mammalian target of rapamycin complex 2 (mTORC2) has been identified as a major regulator of bladder cancer cell migration and invasion. Upstream pathways that mediate mTORC2 activation remain poorly defined. Urokinase-type plasminogen activator receptor (uPAR) is a GPI-anchored membrane protein and known activator of cell-signaling. We identified increased uPAR expression in 94% of invasive human bladder cancers and in 54-71% of non-invasive bladder cancers, depending on grade. Normal urothelium was uPAR-immunonegative. Analysis of publicly available datasets identified uPAR gene amplification or mRNA upregulation in a subset of bladder cancer patients with reduced overall survival. Using biochemical approaches, we showed that uPAR activates mTORC2 in bladder cancer cells. Highly invasive bladder cancer cell lines, including T24, J82 and UM-UC-3 cells, showed increased uPAR mRNA expression and protein levels compared with the less aggressive cell lines, UROtsa and RT4. uPAR gene-silencing significantly reduced phosphorylation of Serine-473 in Akt, an mTORC2 target. uPAR gene-silencing also reduced bladder cancer cell migration and Matrigel invasion. S473 phosphorylation was observed by immunohistochemistry in human bladder cancers only when the tumors expressed high levels of uPAR. S473 phosphorylation was not controlled by uPAR in bladder cancer cell lines that are PTEN-negative; however, this result probably did not reflect altered mTORC2 regulation. Instead, PTEN deficiency de-repressed alternative kinases that phosphorylate S473. Our results suggest that uPAR and mTORC2 are components of a single cell-signaling pathway. Targeting uPAR or mTORC2 may be beneficial in patients with bladder cancer. Copyright © 2016. Published by Elsevier Inc.

Proteinase-activated receptor-4 evoked colorectal analgesia in mice: an endogenously activated feed-back loop in visceral inflammatory pain.

PubMed

Annaházi, A; Dabek, M; Gecse, K; Salvador-Cartier, C; Polizzi, A; Rosztóczy, A; Róka, R; Theodorou, V; Wittmann, T; Bueno, L; Eutamene, H

2012-01-01

Activation of proteinase-activated receptor-4 (PAR-4) from the colonic lumen has an antinociceptive effect to colorectal distension (CRD) in mice in basal conditions. We aimed to determine the functional localization of the responsible receptors and to test their role in two different hyperalgesia models. Mice received PAR-4 activating peptide (PAR-4-AP, AYPGKF-NH(2)) or vehicle intraperitoneally (IP), and abdominal EMG response to CRD was measured. The next group received PAR-4-AP intracolonically (IC) with or without 2,4,6-triaminopyrimidine, a chemical tight junction blocker, before CRD. The SCID mice were used to test the role of lymphocytes in the antihyperalgesic effect. The effects of PAR-4-AP and PAR-4-antagonist (P4pal-10) were evaluated in water avoidance stress (WAS) model and low grade 2,4,6-trinitrobenzene sulfonic acid (TNBS) colitis. Spinal Fos protein expression was visualized by immunohistochemistry. The antinociceptive effect of PAR-4-AP disappeared when was administrered IP, or with the blockade of colonic epithelial tight junctions, suggesting that PAR-4-AP needs to reach directly the nerve terminals in the colon. The CRD-induced spinal Fos overexpression was reduced by 43% by PAR-4-AP. The PAR-4-AP was antihyperalgesic in both hyperalgesia models and in mice with impaired lymphocytes. The PAR-4-antagonist significantly increased the TNBS, but not the WAS-induced colonic hyperalgesia. The antinociceptive effect of PAR-4-AP depends on its penetration to the colonic mucosa. The PAR-4 activation is endogenously involved as a feedback loop to attenuate inflammatory colonic hyperalgesia to CRD. © 2011 Blackwell Publishing Ltd.

Effects of silenced PAR-2 on cell proliferation, invasion and metastasis of esophageal cancer.

PubMed

Chen, Jinmei; Xie, Liqun; Zheng, Yanmin; Liu, Caihong

2017-10-01

The present study aimed to investigate the effect of protease-activated receptor 2 (PAR-2) on cell proliferation, invasion and metastasis in the esophageal EC109 cell line. Two short hairpin RNA (shRNA) expression plasmids were constructed based on the PAR-2 mRNA sequence in humans, and they were transfected into the EC109 esophageal cancer cell line, and the stable interference cell line (shRNA-PAR-2 EC109) was obtained by puromycin selection. Following transfection of PAR-2 shRNA-1, PAR-2 expression was significantly downregulated in mRNA level and protein level in EC109 cells (P<0.05). The proliferation of EC109 cells transfected with PAR-2 shRNA was significantly lower than the negative control group (P<0.05). At 24, 48 and 72 h, the ratio of proliferation inhibition was 15.92, 24.89 and 32.28%, respectively. Compared with the control group, S-phase arrest was observed in cells transfected with shRNA-PAR-2. The ratio of cells in the S phase was 32.79±4.06, 26.54±1.37 and 33.45±2.46% at 24, 48 and 72 h, respectively. For invasion, the number of invasive cells was significantly lower in shRNA-PAR2-2 cells compared with the control group (P<0.05). For metastasis assay, the number of invasive cells was significantly lower in shRNA-PAR2-2 cells compared with the control group (P<0.01). In the present study, the PAR-2 shRNA plasmid was constructed successfully, which can significantly downregulate PAR-2 expression in EC109 cells. Subsequent to silencing of PAR-2, the proliferation of EC109 cells was inhibited and the capabilities of invasion and migration were reduced. It is indicated that PAR-2 may be a potential target in esophageal cancer.

Autocrine Extra-Pancreatic Trypsin 3 Secretion Promotes Cell Proliferation and Survival in Esophageal Adenocarcinoma

PubMed Central

Han, Song; Lee, Constance W.; Trevino, Jose G.; Hughes, Steven J.; Sarosi, George A.

2013-01-01

Trypsin or Tumor associated trypsin (TAT) activation of Protease-activated receptor 2 (PAR-2) promotes tumor cell proliferation in gastrointestinal cancers. The role of the trypsin/PAR-2 network in esophageal adenocarcinoma (EA) development has not yet been investigated. The aim of this study is to investigate the role of trypsin/PAR-2 activation in EA tumorogenesis and therapy. We found that esophageal adenocarcinoma cells (EACs) and Barrett’s Metaplasia (BART) expressed high levels of type 3 extra-pancreatic trypsinogen (PRSS3), a novel type of TAT. Activity of secreted trypsin was detected in cultured media from EA OE19 and OE33 cultures but not from BART culture. Surface PAR-2 expression in BART and EACs was confirmed by both flow cytometry and immunofluorescence. Trypsin induced cell proliferation (∼ 2 fold; P<0.01) in all tested cell lines at a concentration of 10 nM. Inhibition of PAR-2 activity in EACs via the PAR-2 antagonist ENMD (500 µM), anti-PAR2 antibody SAM-11 (2 µg/ml), or siRNA PAR-2 knockdown, reduced cell proliferation and increased apoptosis by up to 4 fold (P<0.01). Trypsin stimulation led to phosphorylation of ERK1/2, suggesting involvement of MAPK pathway in PAR-2 signal transduction. Inhibition of PAR-2 activation or siRNA PAR-2 knockdown in EACs prior to treatment with 5 FU reduced cell viability of EACs by an additional 30% (P<0.01) compared to chemotherapy alone. Our data suggest that extra-pancreatic trypsinogen 3 is produced by EACs and activates PAR-2 in an autocrine manner. PAR-2 activation increases cancer cell proliferation, and promotes cancer cell survival. Targeting the trypsin activated PAR-2 pathway in conjunction with current chemotherapeutic agents may be a viable therapeutic strategy in EA. PMID:24146905

Effects of silenced PAR-2 on cell proliferation, invasion and metastasis of esophageal cancer

PubMed Central

Chen, Jinmei; Xie, Liqun; Zheng, Yanmin; Liu, Caihong

2017-01-01

The present study aimed to investigate the effect of protease-activated receptor 2 (PAR-2) on cell proliferation, invasion and metastasis in the esophageal EC109 cell line. Two short hairpin RNA (shRNA) expression plasmids were constructed based on the PAR-2 mRNA sequence in humans, and they were transfected into the EC109 esophageal cancer cell line, and the stable interference cell line (shRNA-PAR-2 EC109) was obtained by puromycin selection. Following transfection of PAR-2 shRNA-1, PAR-2 expression was significantly downregulated in mRNA level and protein level in EC109 cells (P<0.05). The proliferation of EC109 cells transfected with PAR-2 shRNA was significantly lower than the negative control group (P<0.05). At 24, 48 and 72 h, the ratio of proliferation inhibition was 15.92, 24.89 and 32.28%, respectively. Compared with the control group, S-phase arrest was observed in cells transfected with shRNA-PAR-2. The ratio of cells in the S phase was 32.79±4.06, 26.54±1.37 and 33.45±2.46% at 24, 48 and 72 h, respectively. For invasion, the number of invasive cells was significantly lower in shRNA-PAR2-2 cells compared with the control group (P<0.05). For metastasis assay, the number of invasive cells was significantly lower in shRNA-PAR2-2 cells compared with the control group (P<0.01). In the present study, the PAR-2 shRNA plasmid was constructed successfully, which can significantly downregulate PAR-2 expression in EC109 cells. Subsequent to silencing of PAR-2, the proliferation of EC109 cells was inhibited and the capabilities of invasion and migration were reduced. It is indicated that PAR-2 may be a potential target in esophageal cancer. PMID:28943918

The Role of PAR2 in TGF-β1-Induced ERK Activation and Cell Motility

PubMed Central

Ungefroren, Hendrik; Witte, David; Fiedler, Christian; Gädeken, Thomas; Kaufmann, Roland; Lehnert, Hendrik

2017-01-01

Background: Recently, the expression of proteinase-activated receptor 2 (PAR2) has been shown to be essential for activin receptor-like kinase 5 (ALK5)/SMAD-mediated signaling and cell migration by transforming growth factor (TGF)-β1. However, it is not known whether activation of non-SMAD TGF-β signaling (e.g., RAS–RAF–MEK–extracellular signal-regulated kinase (ERK) signaling) is required for cell migration and whether it is also dependent on PAR2. Methods: RNA interference was used to deplete cells of PAR2, followed by xCELLigence technology to measure cell migration, phospho-immunoblotting to assess ERK1/2 activation, and co-immunoprecipitation to detect a PAR2–ALK5 physical interaction. Results: Inhibition of ERK signaling with the MEK inhibitor U0126 blunted the ability of TGF-β1 to induce migration in pancreatic cancer Panc1 cells. ERK activation in response to PAR2 agonistic peptide (PAR2–AP) was strong and rapid, while it was moderate and delayed in response to TGF-β1. Basal and TGF-β1-dependent ERK, but not SMAD activation, was blocked by U0126 in Panc1 and other cell types indicating that ERK activation is downstream or independent of SMAD signaling. Moreover, cellular depletion of PAR2 in HaCaT cells strongly inhibited TGF-β1-induced ERK activation, while the biased PAR2 agonist GB88 at 10 and 100 µM potentiated TGF-β1-dependent ERK activation and cell migration. Finally, we provide evidence for a physical interaction between PAR2 and ALK5. Our data show that both PAR2–AP- and TGF-β1-induced cell migration depend on ERK activation, that PAR2 expression is crucial for TGF-β1-induced ERK activation, and that the functional cooperation of PAR2 and TGF-β1 involves a physical interaction between PAR2 and ALK5. PMID:29261154

Prohibitin is involved in the activated internalization and degradation of protease-activated receptor 1.

PubMed

Wang, Yan-Jie; Guo, Xiao-Long; Li, Sheng-An; Zhao, Yu-Qi; Liu, Zi-Chao; Lee, Wen-Hui; Xiang, Yang; Zhang, Yun

2014-07-01

The protease-activated receptor 1 (PAR1) is a G-protein-coupled receptor that is irreversibly activated by either thrombin or metalloprotease 1. Due this irrevocable activation, activated internalization and degradation are critical for PAR1 signaling termination. Prohibitin (PHB) is an evolutionarily conserved, ubiquitously expressed, pleiotropic protein and belongs to the stomatin/prohibitin/flotillin/HflK/C (SPFH) domain family. In a previous study, we found that PHB localized on the platelet membrane and participated in PAR1-mediated human platelet aggregation, suggesting that PHB likely regulates the signaling of PAR1. Unfortunately, PHB's exact function in PAR1 internalization and degradation is unclear. In the current study, flow cytometry revealed that PHB expressed on the surface of endothelial cells (HUVECs) but not cancer cells (MDA-MB-231). Further confocal microscopy revealed that PHB dynamically associates with PAR1 in a time-dependent manner following induction with PAR1-activated peptide (PAR1-AP), though differently between HUVECs and MDA-MB-231 cells. Depletion of PHB by RNA interference significantly inhibited PAR1 activated internalization and led to sustained Erk1/2 phosphorylation in the HUVECs; however, a similar effect was not observed in MDA-MB-231 cells. For both the endothelial and cancel cells, PHB repressed PAR1 degradation, while knockdown of PHB led to increased PAR1 degradation, and PHB overexpression inhibited PAR1 degradation. These results suggest that persistent PAR1 signaling due to the absence of membrane PHB and decreased PAR1 degradation caused by the upregulation of intracellular PHB in cancer cells (such as MDA-MB-231 cells) may render cells highly invasive. As such, PHB may be a novel target in future anti-cancer therapeutics, or in more refined cancer malignancy diagnostics. Copyright © 2014 Elsevier B.V. All rights reserved.

Magnetic activity and radial velocity filtering of young Suns: the weak-line T-Tauri stars Par 1379 and Par 2244

NASA Astrophysics Data System (ADS)

Hill, C. A.; Carmona, A.; Donati, J.-F.; Hussain, G. A. J.; Gregory, S. G.; Alencar, S. H. P.; Bouvier, J.; The Matysse Collaboration

2017-12-01

We report the results of our spectropolarimetric monitoring of the weak-line T-Tauri stars (wTTSs) Par 1379 and Par 2244, within the MaTYSSE (Magnetic Topologies of Young Stars and the Survival of close-in giant Exoplanets) programme. Both stars are of a similar mass (1.6 and 1.8 M⊙) and age (1.8 and 1.1 Myr), with Par 1379 hosting an evolved low-mass dusty circumstellar disc, and with Par 2244 showing evidence of a young debris disc. We detect profile distortions and Zeeman signatures in the unpolarized and circularly polarized lines for each star, and have modelled their rotational modulation using tomographic imaging, yielding brightness and magnetic maps. We find that Par 1379 harbours a weak (250 G), mostly poloidal field tilted 65° from the rotation axis. In contrast, Par 2244 hosts a stronger field (860 G) split 3:2 between poloidal and toroidal components, with most of the energy in higher order modes, and with the poloidal component tilted 45° from the rotation axis. Compared to the lower mass wTTSs, V819 Tau and V830 Tau, Par 2244 has a similar field strength, but is much more complex, whereas the much less complex field of Par 1379 is also much weaker than any other mapped wTTS. We find moderate surface differential rotation of 1.4× and 1.8× smaller than Solar, for Par 1379 and Par 2244, respectively. Using our tomographic maps to predict the activity-related radial velocity (RV) jitter, and filter it from the RV curves, we find RV residuals with dispersions of 0.017 and 0.086 km s-1 for Par 1379 and Par 2244, respectively. We find no evidence for close-in giant planets around either star, with 3σ upper limits of 0.56 and 3.54 MJup (at an orbital distance of 0.1 au).

Regulation of protease-activated receptor 1 signaling by the adaptor protein complex 2 and R4 subfamily of regulator of G protein signaling proteins.

PubMed

Chen, Buxin; Siderovski, David P; Neubig, Richard R; Lawson, Mark A; Trejo, Joann

2014-01-17

The G protein-coupled protease-activated receptor 1 (PAR1) is irreversibly proteolytically activated by thrombin. Hence, the precise regulation of PAR1 signaling is important for proper cellular responses. In addition to desensitization, internalization and lysosomal sorting of activated PAR1 are critical for the termination of signaling. Unlike most G protein-coupled receptors, PAR1 internalization is mediated by the clathrin adaptor protein complex 2 (AP-2) and epsin-1, rather than β-arrestins. However, the function of AP-2 and epsin-1 in the regulation of PAR1 signaling is not known. Here, we report that AP-2, and not epsin-1, regulates activated PAR1-stimulated phosphoinositide hydrolysis via two different mechanisms that involve, in part, a subset of R4 subfamily of "regulator of G protein signaling" (RGS) proteins. A significantly greater increase in activated PAR1 signaling was observed in cells depleted of AP-2 using siRNA or in cells expressing a PAR1 (420)AKKAA(424) mutant with defective AP-2 binding. This effect was attributed to AP-2 modulation of PAR1 surface expression and efficiency of G protein coupling. We further found that ectopic expression of R4 subfamily members RGS2, RGS3, RGS4, and RGS5 reduced activated PAR1 wild-type signaling, whereas signaling by the PAR1 AKKAA mutant was minimally affected. Intriguingly, siRNA-mediated depletion analysis revealed a function for RGS5 in the regulation of signaling by the PAR1 wild type but not the AKKAA mutant. Moreover, activation of the PAR1 wild type, and not the AKKAA mutant, induced Gαq association with RGS3 via an AP-2-dependent mechanism. Thus, AP-2 regulates activated PAR1 signaling by altering receptor surface expression and through recruitment of RGS proteins.

Protease-Activated Receptor-2 Is Associated with Terminal Differentiation of Epidermis and Eccrine Sweat Glands

PubMed Central

Shin, Yong-Sup; Kim, Hyung Won; Kim, Chang Deok; Kim, Hyun-Woo; Park, Jin Woon; Jung, Sunggyun; Lee, Jeung-Hoon; Ko, Young-Kwon

2015-01-01

Background Protease-activated receptor 2 (PAR-2) participates in various biological activities, including the regulation of epidermal barrier homeostasis, inflammation, pain perception, and melanosome transfer in the skin. Objective To evaluate the basic physiological role of PAR-2 in skin. Methods We investigated PAR-2 expression in human epidermis, skin tumors, and cultured epidermal cells using western blot and immunohistochemical analysis. Additionally, we examined the effect of the PAR-2 agonist, SLIGRL-NH2, on cultured keratinocytes. Results Strong PAR-2 immunoreactivity was observed in the granular layer of normal human skin and the acrosyringium of the eccrine sweat glands. In contrast, weak PAR-2 immunoreactivity was seen in the granular layer of callused skin and in the duct and gland cells of the eccrine sweat glands. Interestingly, PAR-2 immunoreactivity was very weak or absent in the tumor cells of squamous cell carcinoma (SCC) and syringoma. PAR-2 was detected in primary keratinocytes and SV-40T-transformed human epidermal keratinocytes (SV-HEKs), an immortalized keratinocyte cell line, but not in SCC12 cells. SV-HEKs that were fully differentiated following calcium treatment displayed higher PAR-2 expression than undifferentiated SV-HEKs. Treatment of cultured SV-HEKs with PAR-2 agonist increased loricrin and filaggrin expression, a terminal differentiation marker. Conclusion Our data suggest that PAR-2 is associated with terminal differentiation of epidermis and eccrine sweat glands. PMID:26273149

Protease-Activated Receptor-2 Is Associated with Terminal Differentiation of Epidermis and Eccrine Sweat Glands.

PubMed

Shin, Yong-Sup; Kim, Hyung Won; Kim, Chang Deok; Kim, Hyun-Woo; Park, Jin Woon; Jung, Sunggyun; Lee, Jeung-Hoon; Ko, Young-Kwon; Lee, Young Ho

2015-08-01

Protease-activated receptor 2 (PAR-2) participates in various biological activities, including the regulation of epidermal barrier homeostasis, inflammation, pain perception, and melanosome transfer in the skin. To evaluate the basic physiological role of PAR-2 in skin. We investigated PAR-2 expression in human epidermis, skin tumors, and cultured epidermal cells using western blot and immunohistochemical analysis. Additionally, we examined the effect of the PAR-2 agonist, SLIGRL-NH2, on cultured keratinocytes. Strong PAR-2 immunoreactivity was observed in the granular layer of normal human skin and the acrosyringium of the eccrine sweat glands. In contrast, weak PAR-2 immunoreactivity was seen in the granular layer of callused skin and in the duct and gland cells of the eccrine sweat glands. Interestingly, PAR-2 immunoreactivity was very weak or absent in the tumor cells of squamous cell carcinoma (SCC) and syringoma. PAR-2 was detected in primary keratinocytes and SV-40T-transformed human epidermal keratinocytes (SV-HEKs), an immortalized keratinocyte cell line, but not in SCC12 cells. SV-HEKs that were fully differentiated following calcium treatment displayed higher PAR-2 expression than undifferentiated SV-HEKs. Treatment of cultured SV-HEKs with PAR-2 agonist increased loricrin and filaggrin expression, a terminal differentiation marker. Our data suggest that PAR-2 is associated with terminal differentiation of epidermis and eccrine sweat glands.

PAR-1 contributes to the innate immune response during viral infection

PubMed Central

Antoniak, Silvio; Owens, A. Phillip; Baunacke, Martin; Williams, Julie C.; Lee, Rebecca D.; Weithäuser, Alice; Sheridan, Patricia A.; Malz, Ronny; Luyendyk, James P.; Esserman, Denise A.; Trejo, JoAnn; Kirchhofer, Daniel; Blaxall, Burns C.; Pawlinski, Rafal; Beck, Melinda A.; Rauch, Ursula; Mackman, Nigel

2013-01-01

Coagulation is a host defense system that limits the spread of pathogens. Coagulation proteases, such as thrombin, also activate cells by cleaving PARs. In this study, we analyzed the role of PAR-1 in coxsackievirus B3–induced (CVB3-induced) myocarditis and influenza A infection. CVB3-infected Par1–/– mice expressed reduced levels of IFN-β and CXCL10 during the early phase of infection compared with Par1+/+ mice that resulted in higher viral loads and cardiac injury at day 8 after infection. Inhibition of either tissue factor or thrombin in WT mice also significantly increased CVB3 levels in the heart and cardiac injury compared with controls. BM transplantation experiments demonstrated that PAR-1 in nonhematopoietic cells protected mice from CVB3 infection. Transgenic mice overexpressing PAR-1 in cardiomyocytes had reduced CVB3-induced myocarditis. We found that cooperative signaling between PAR-1 and TLR3 in mouse cardiac fibroblasts enhanced activation of p38 and induction of IFN-β and CXCL10 expression. Par1–/– mice also had decreased CXCL10 expression and increased viral levels in the lung after influenza A infection compared with Par1+/+ mice. Our results indicate that the tissue factor/thrombin/PAR-1 pathway enhances IFN-β expression and contributes to the innate immune response during single-stranded RNA viral infection. PMID:23391721

A reassessment of soluble urokinase-type plasminogen activator receptor in glomerular disease

PubMed Central

Spinale, Joann M.; Mariani, Laura H.; Kapoor, Shiv; Zhang, Jidong; Weyant, Robert; Song, Peter X.; Wong, Hetty N.; Troost, Jonathan P.; Gadegbeku, Crystal A.; Gipson, Debbie S.; Kretzler, Matthias; Nihalani, Deepak; Holzman, Lawrence B.

2014-01-01

It has been suggested that soluble urokinase receptor (suPAR) is a causative circulating factor for and a biomarker of focal and segmental glomerulosclerosis (FSGS). Here we undertook validation of these assumptions in both mouse and human models. Injection of recombinant suPAR in wild-type mice did not induce proteinuria within 24 hours. Moreover, a disease phenotype was not seen in an inducible transgenic mouse model that maintained elevated suPAR concentrations for 6 weeks. Plasma and urine suPAR concentrations were evaluated as clinical biomarkers in 241 patients with glomerular disease from the prospective, longitudinal multi-center observational NEPTUNE cohort. The serum suPAR concentration at baseline inversely correlated with estimated glomerular filtration rate (eGFR) and the urine suPAR/creatinine ratio positively correlated with the urine protein/creatinine ratio. After adjusting for eGFR and urine protein, neither the serum nor urine suPAR level was an independent predictor of FSGS histopathology. A multivariable mixed-effects model of longitudinal data evaluated the association between the change in serum suPAR concentration from baseline with eGFR. After adjusting for baseline suPAR concentration, age, gender, proteinuria and time, the change in suPAR from baseline was associated with eGFR, but this association was not different for patients with FSGS as compared to other diagnoses. Thus, these results do not support a pathological role for suPAR in FSGS. PMID:25354239

A reassessment of soluble urokinase-type plasminogen activator receptor in glomerular disease.

PubMed

Spinale, Joann M; Mariani, Laura H; Kapoor, Shiv; Zhang, Jidong; Weyant, Robert; Song, Peter X; Wong, Hetty N; Troost, Jonathan P; Gadegbeku, Crystal A; Gipson, Debbie S; Kretzler, Matthias; Nihalani, Deepak; Holzman, Lawrence B

2015-03-01

It has been suggested that soluble urokinase receptor (suPAR) is a causative circulating factor for and a biomarker of focal and segmental glomerulosclerosis (FSGS). Here we undertook validation of these assumptions in both mouse and human models. Injection of recombinant suPAR in wild-type mice did not induce proteinuria within 24 h. Moreover, a disease phenotype was not seen in an inducible transgenic mouse model that maintained elevated suPAR concentrations for 6 weeks. Plasma and urine suPAR concentrations were evaluated as clinical biomarkers in 241 patients with glomerular disease from the prospective, longitudinal multicenter observational NEPTUNE cohort. The serum suPAR concentration at baseline inversely correlated with estimated glomerular filtration rate (eGFR) and the urine suPAR/creatinine ratio positively correlated with the urine protein/creatinine ratio. After adjusting for eGFR and urine protein, neither the serum nor urine suPAR level was an independent predictor of FSGS histopathology. A multivariable mixed-effects model of longitudinal data evaluated the association between the change in serum suPAR concentration from baseline with eGFR. After adjusting for baseline suPAR concentration, age, gender, proteinuria, and time, the change in suPAR from baseline was associated with eGFR, but this association was not different for patients with FSGS as compared with other diagnoses. Thus these results do not support a pathological role for suPAR in FSGS.

Protease-activated receptor 2 modulates proliferation and invasion of oral squamous cell carcinoma cells.

PubMed

Al-Eryani, Kamal; Cheng, Jun; Abé, Tatsuya; Maruyama, Satoshi; Yamazaki, Manabu; Babkair, Hamzah; Essa, Ahmed; Saku, Takashi

2015-07-01

Based on our previous finding that protease-activated receptor 2 (PAR-2) regulates hemophagocytosis of oral squamous cell carcinoma (SCC) cells, which induces their heme oxygenase 1-dependent keratinization, we have formulated a hypothesis that PAR-2 functions in wider activities of SCC cells. To confirm this hypothesis, we investigated immunohistochemical profiles of PAR-2 in oral SCC tissues and its functional roles in cell proliferation and invasion in SCC cells in culture. The PAR-2 expression modes were determined in 48 surgical tissue specimens of oral SCC. Using oral SCC-derived cell systems, we determined both gene and protein expression levels of PAR-2. SCC cell proliferation and invasive properties were also examined in conditions in which PAR-2 was activated by the synthetic peptide SLIGRL. PAR-2 was immunolocalized in oral SCC and carcinoma in situ cells, especially in those on the periphery of carcinoma cell foci (100% of cases), but not in normal oral epithelia. Its expression at both gene and protein levels was confirmed in 3 oral SCC cell lines including ZK-1. Activation of PAR-2 induced ZK-1 cell proliferation in a dose-dependent manner. PAR-2-activated ZK-1 cells invaded faster than nonactivated ones. The expression of PAR-2 is specific to oral malignancies, and PAR-2 regulates the growth and invasion of oral SCC cells. Copyright © 2015 Elsevier Inc. All rights reserved.

ParFit: A Python-Based Object-Oriented Program for Fitting Molecular Mechanics Parameters to ab Initio Data.

PubMed

Zahariev, Federico; De Silva, Nuwan; Gordon, Mark S; Windus, Theresa L; Dick-Perez, Marilu

2017-03-27

A newly created object-oriented program for automating the process of fitting molecular-mechanics parameters to ab initio data, termed ParFit, is presented. ParFit uses a hybrid of deterministic and stochastic genetic algorithms. ParFit can simultaneously handle several molecular-mechanics parameters in multiple molecules and can also apply symmetric and antisymmetric constraints on the optimized parameters. The simultaneous handling of several molecules enhances the transferability of the fitted parameters. ParFit is written in Python, uses a rich set of standard and nonstandard Python libraries, and can be run in parallel on multicore computer systems. As an example, a series of phosphine oxides, important for metal extraction chemistry, are parametrized using ParFit. ParFit is in an open source program available for free on GitHub ( https://github.com/fzahari/ParFit ).

Military Applications of Fiber Optics Technology

DTIC Science & Technology

1989-05-01

Research Projects Agency DNA Defense Nuclear Agency EMI Electromagnetic interference EMP Electromagnetic pulse FET Field effect transistor FOFA Follow...Organization SEED Self electro-optic effect device TBM Tactical ballistic missile TOW Tube launched, optically tracked, wire-guided UAV Unmanned aerial vehicle...systems, coupled with novel but effective transducing technology, have set the stage for a powerful class of fiber optic sensors. 8 Optical fibers have

Guide to Canadian Aerospace Related Industries,

DTIC Science & Technology

1986-02-28

Contract with Environmental Research and Code: ANA Development (US). Address: 240 Brooksbank Ave Digital Radar - Contract with Fundacao Educacional ...range from coal ings. The company is especially well known for its innovative engi- mining (methane) applications in Gillette, Wyoming to carbon...an order of magnitude higher than those provided by Atlantis also offers R&D and manufacturing services, especially standard tunnel diode pulse

Stanford MFEL and Near Infrared Science Center

DTIC Science & Technology

2011-01-28

guiding procedures for restoration of hearing— cochlear implants. Multifaceted approaches have been taken to understand the molecular and cellular...accompanying phenomena of cavitation, liquid flow and heat transfer in various biological tissues. In the field of laser surgery with ultrashort pulses...using yeast cell surface display, the Cochran group has generated EGF mutant libraries and have screened them by flow cytometry using fluorescently

Plasma devices to guide and collimate a high density of MeV electrons.

PubMed

Kodama, R; Sentoku, Y; Chen, Z L; Kumar, G R; Hatchett, S P; Toyama, Y; Cowan, T E; Freeman, R R; Fuchs, J; Izawa, Y; Key, M H; Kitagawa, Y; Kondo, K; Matsuoka, T; Nakamura, H; Nakatsutsumi, M; Norreys, P A; Norimatsu, T; Snavely, R A; Stephens, R B; Tampo, M; Tanaka, K A; Yabuuchi, T

2004-12-23

The development of ultra-intense lasers has facilitated new studies in laboratory astrophysics and high-density nuclear science, including laser fusion. Such research relies on the efficient generation of enormous numbers of high-energy charged particles. For example, laser-matter interactions at petawatt (10(15) W) power levels can create pulses of MeV electrons with current densities as large as 10(12) A cm(-2). However, the divergence of these particle beams usually reduces the current density to a few times 10(6) A cm(-2) at distances of the order of centimetres from the source. The invention of devices that can direct such intense, pulsed energetic beams will revolutionize their applications. Here we report high-conductivity devices consisting of transient plasmas that increase the energy density of MeV electrons generated in laser-matter interactions by more than one order of magnitude. A plasma fibre created on a hollow-cone target guides and collimates electrons in a manner akin to the control of light by an optical fibre and collimator. Such plasma devices hold promise for applications using high energy-density particles and should trigger growth in charged particle optics.

The role of protease-activated receptor-2 on pulmonary neutrophils in the innate immune response to cockroach allergen

PubMed Central

2012-01-01

Background Serine proteases in German cockroach (GC) have been shown to mediate allergic airway inflammation through the activation of protease activated receptor (PAR)-2. Neutrophils play an important role in regulating the innate immune response, and are recruited into the airways following GC frass exposure. As such, we investigated the role of PAR-2 in airway neutrophil recruitment, activation and cytokine production following allergen exposure. Methods Wild type and PAR-2-deficient mice were administered a single intratracheal instillation of PBS or GC frass and neutrophil recruitment, expression of PAR-2, CD80, CD86, and MHC class II were assessed by flow cytometry and levels of tumor necrosis factor (TNF)α was assessed by ELISA. Uptake of AlexaFluor 405-labeled GC frass by neutrophils was performed by flow cytometry. Results Neutrophil recruitment in the lung and airways following GC frass exposure was significantly decreased in PAR-2-deficient mice compared to wild type mice. GC frass exposure increased the level of PAR-2 on pulmonary neutrophils and increased numbers of PAR-2-positive neutrophils were found in the lungs; however PAR-2 did not play a role in meditating allergen uptake. Comparing wild type and PAR-2-deficient mice, we found that a single exposure to GC frass increased levels of CD80 and CD86 on pulmonary neutrophils, an effect which was independent of PAR-2 expression. Neutrophils isolated from the whole lungs of naïve PAR-2-deficient mice treated ex vivo with GC frass produced significantly less TNFα than in similarly treated wild type neutrophils. Lastly, neutrophils were isolated from the bronchoalveolar lavage fluid of wild type and PAR-2-deficient mice following a single intratracheal exposure to GC frass. Airway neutrophils from PAR-2-deficient mice released substantially decreased levels of TNFα, suggesting a role for PAR-2 in neutrophil-derived cytokine production. Conclusions Together these data suggest PAR-2 expression can be upregulated on lung neutrophils following allergen exposure and the consequence is altered release of TNFα which could drive the early innate immune response. PMID:22954301

SU-F-J-225: Histology Study of MR Guided Pulsed Focused Ultrasound On Treatment of Prostate Cancer in Vivo

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

Chen, L; Cvetkovic, D; Chen, X

Purpose: Our previous study demonstrated significant tumor growth delay in the mice treated with pulsed high intensity focused ultrasound (pHIFU). The purpose of this study is to understand the cell killing mechanisms of pHIFU. Methods: Prostate cancer cells (LNCaP), were grown orthotopically in 17 nude mice. Tumor-bearing mice were treated using pHIFU with an acoustic power of 25W, pulse width 100msec and 300 pulses in one sonication under MR guidance. Mutiple sonications were used to cover the whole tumor volume. The temperature (less than 40 degree centigrade in the focal spot) was monitored using MR thermometry. Animals were euthanized atmore » pre-determined time points (n=2) after treatment: 0 hours; 6 hrs; 24 hrs; 48 hrs; 4 days and 7 days. Two tumorbearing mice were used as control. Three tumor-bearing mice were treated with radiation (RT, 2 Gy) using 6 MV photon beams. RT treated mice were euthanized at 0 hr, 6 hrs and 24 hrs. The tumors were processed for immunohistochemical (IHC) staining for PARP (a surrogate of apoptosis). A multispectral imaging analysis system was used to quantify the expression of PARP staining. Cell apoptosis was calculated based on the PARP expression level using the DAB analysis software. Results: Our data showed that PARP related apoptosis peaked at 48 hrs and 7 days in pHIFU treated mice, which is comparable to that for the RT group at 24 hrs. The preliminary results from this study were consistent with our previous study on tumor growth delay using pHIFU. Conclusion: Our results demonstrated that non-thermal pHIFU increased apoptotic tumor cell death through the PARP related pathway. MR guided pHIFU may have a great potential as a safe, noninvasive treatment modality for cancer therapy. This treatment modality may synergize with PARP inhibitors to achieve better therapeutic result.« less

Image-guided smart laser system for precision implantation of cells in cartilage

NASA Astrophysics Data System (ADS)

Katta, Nitesh; Rector, John A.; Gardner, Michael R.; McElroy, Austin B.; Choy, Kevin C.; Crosby, Cody; Zoldan, Janet; Milner, Thomas E.

2017-03-01

State-of-the-art treatment for joint diseases like osteoarthritis focus on articular cartilage repair/regeneration by stem cell implantation therapy. However, the technique is limited by a lack of precision in the physician's imaging and cell deposition toolkit. We describe a novel combination of high-resolution, rapid scan-rate optical coherence tomography (OCT) alongside a short-pulsed nanosecond thulium (Tm) laser for precise cell seeding in cartilage. The superior beam quality of thulium lasers and wavelength of operation 1940 nm offers high volumetric tissue removal rates and minimizes the residual thermal footprint. OCT imaging enables targeted micro-well placement, precise cell deposition, and feature contrast. A bench-top system is constructed using a 15 W, 1940 nm, nanosecond-pulsed Tm fiber laser (500 μJ pulse energy, 100 ns pulse duration, 30kHz repetition rate) for removing tissue, and a swept source laser (1310 ± 70 nm, 100 kHz sweep rate) for OCT imaging, forming a combined Tm/OCT system - a "smart laser knife". OCT assists the smart laser knife user in characterizing cartilage to inform micro-well placement. The Tm laser creates micro-wells (2.35 mm diameter length, 1.5 mm width, 300 μm deep) and micro-incisions (1 mm wide, 200 μm deep) while OCT image-guidance assists and demonstrates this precision cutting and cell deposition with real-time feedback. To test micro-well creation and cell deposition protocol, gelatin phantoms are constructed mimicking cartilage optical properties and physiological structure. Cell viability is then assessed to illustrate the efficacy of the hydrogel deposition. Automated OCT feedback is demonstrated for cutting procedures to avoid important surface/subsurface structures. This bench-top smart laser knife system described here offers a new image-guided approach to precise stem cell seeding that can enhance the efficacy of articular cartilage repair.

The new RLA test status

NASA Astrophysics Data System (ADS)

Smith, D. L.; Mazarakis, M. G.; Skogmo, P.; Bennett, L. F.; Olson, W. R.; George, M.; Harden, M. J.; Turman, B. N.; Moya, S. A.; Henderson, J. L.

The Recirculating Linear Accelerator (RLA) is returning to operation with a new relativistic electron beam (REB) injector and a modified accelerating cavity. Upon completion of our pulsed-power test program, we will capture the injected beam on an Ion Focussed Regime (IFR) guiding channel in either a spiral or a closed racetrack drift tube. The relativistic beam will recirculate for four passes through two accelerating cavities, in phase with the ringing cavity voltage, and increase to 8--12 MeV before being extracted. We designed the METGLAS ribbon-wound core, inductively isolated, four-stage injector to produce beam parameters of 4 MeV, 10--20 kA, and 40--55 ns FWHM. The three-line radial cavity is being modified to improve the 1-MV accelerating pulse shape while an advanced cavity design study is in progress. This is a continuation of the Sandia National Laboratory program to develop compact, high-voltage gradient, linear induction accelerators. The RLA concept is based on guiding an injected REB with an IFR channel. This channel is formed from a plasma created with a low energy electron beam inside a beam line containing about 2 x 10(exp -4) Torr of argon. The REB is injected onto the IFR channel and is transported down the beamline through a water dielectric accelerating cavity based on the ET-2 design. If the round-tip path of the beam matches the period of the cavity, the REB can be further accelerated by the ringing waveform on every subsequent pass. We have installed the new REB injector because we need a higher amplitude, longer duration, flat-topped pulse shape with a colder beam than that produced by the previous injector. We made extensive use of computer simulations in the form of network solver and electrostatic field stress analysis codes to aid in the design and modifications for the new RLA. The pulsed-power performance of the RLA injector and cavity and the associated driving hardware are discussed.

Increased mast cell expression of PAR-2 in skin inflammatory diseases and release of IL-8 upon PAR-2 activation.

PubMed

Carvalho, Ricardo Filipe da Silva; Nilsson, Gunnar; Harvima, Ilkka Tapani

2010-02-01

Mast cells are increasingly present in the lesional skin of chronic skin inflammatory diseases including psoriasis and basal cell carcinoma (BCC). It has previously been shown that proteinase-activated receptor (PAR)-2 is expressed by mast cells, and tryptase is a potent activator of this receptor. In this study, skin biopsies from both healthy-looking and lesional skin of patients with psoriasis and superficial spreading BCC were collected and the expression of PAR-2 immunoreactivity in tryptase-positive mast cells was analysed. PAR-2 expression was confirmed in vitro in different mast cell populations. Cord-blood derived mast cells (CBMC) were stimulated with a PAR-2 activating peptide, 2-furoyl-LIGRLO-NH(2). Consequently, IL-8 and histamine production was analysed in the supernatants. We observed a significant increase in the percentage of mast cells expressing PAR-2 in the lesional skin of psoriasis and BCC patients compared with the healthy-looking skin. HMC-1.2, LAD-2 and CBMC mast cells all expressed PAR-2 both intracellularly and on the cell surface. CBMC activation with the PAR-2 activating peptide resulted in an increased secretion of IL-8, but no histamine release was observed. Furthermore, both PAR-2 and IL-8 were co-localized to the same tryptase-positive mast cells in the lesional BCC skin. These results show that mast cells express increased levels of PAR-2 in chronic skin inflammation. Also, mast cells can be activated by a PAR-2 agonist to secrete IL-8, a chemokine which can contribute to the progress of inflammation.

Adaptor Protein Complex-2 (AP-2) and Epsin-1 Mediate Protease-activated Receptor-1 Internalization via Phosphorylation- and Ubiquitination-dependent Sorting Signals*

PubMed Central

Chen, Buxin; Dores, Michael R.; Grimsey, Neil; Canto, Isabel; Barker, Breann L.; Trejo, JoAnn

2011-01-01

Signaling by protease-activated receptor-1 (PAR1), a G protein-coupled receptor (GPCR) for thrombin, is regulated by desensitization and internalization. PAR1 desensitization is mediated by β-arrestins, like most classic GPCRs. In contrast, internalization of PAR1 occurs through a clathrin- and dynamin-dependent pathway independent of β-arrestins. PAR1 displays two modes of internalization. Constitutive internalization of unactivated PAR1 is mediated by the clathrin adaptor protein complex-2 (AP-2), where the μ2-adaptin subunit binds directly to a tyrosine-based motif localized within the receptor C-tail domain. However, AP-2 depletion only partially inhibits agonist-induced internalization of PAR1, suggesting a function for other clathrin adaptors in this process. Here, we now report that AP-2 and epsin-1 are both critical mediators of agonist-stimulated PAR1 internalization. We show that ubiquitination of PAR1 and the ubiquitin-interacting motifs of epsin-1 are required for epsin-1-dependent internalization of activated PAR1. In addition, activation of PAR1 promotes epsin-1 de-ubiquitination, which may increase its endocytic adaptor activity to facilitate receptor internalization. AP-2 also regulates activated PAR1 internalization via recognition of distal C-tail phosphorylation sites rather than the canonical tyrosine-based motif. Thus, AP-2 and epsin-1 are both required to promote efficient internalization of activated PAR1 and recognize discrete receptor sorting signals. This study defines a new pathway for internalization of mammalian GPCRs. PMID:21965661

Planar Cell Polarity Breaks the Symmetry of PAR Protein Distribution prior to Mitosis in Drosophila Sensory Organ Precursor Cells.

PubMed

Besson, Charlotte; Bernard, Fred; Corson, Francis; Rouault, Hervé; Reynaud, Elodie; Keder, Alyona; Mazouni, Khalil; Schweisguth, François

2015-04-20

During development, cell-fate diversity can result from the unequal segregation of fate determinants at mitosis. Polarization of the mother cell is essential for asymmetric cell division (ACD). It often involves the formation of a cortical domain containing the PAR complex proteins Par3, Par6, and atypical protein kinase C (aPKC). In the fly notum, sensory organ precursor cells (SOPs) divide asymmetrically within the plane of the epithelium and along the body axis to generate two distinct cells. Fate asymmetry depends on the asymmetric localization of the PAR complex. In the absence of planar cell polarity (PCP), SOPs divide with a random planar orientation but still asymmetrically, showing that PCP is dispensable for PAR asymmetry at mitosis. To study when and how the PAR complex localizes asymmetrically, we have used a quantitative imaging approach to measure the planar polarization of the proteins Bazooka (Baz, fly Par3), Par6, and aPKC in living pupae. By using imaging of functional GFP-tagged proteins with image processing and computational modeling, we find that Baz, Par6, and aPKC become planar polarized prior to mitosis in a manner independent of the AuroraA kinase and that PCP is required for the planar polarization of Baz, Par6, and aPKC during interphase. This indicates that a "mitosis rescue" mechanism establishes asymmetry at mitosis in PCP mutants. This study therefore identifies PCP as the initial symmetry-breaking signal for the planar polarization of PAR proteins in asymmetrically dividing SOPs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prognosis in adenocarcinomas of lower oesophagus, gastro-oesophageal junction and cardia evaluated by uPAR-immunohistochemistry.

PubMed

Laerum, Ole Didrik; Ovrebo, Kjell; Skarstein, Arne; Christensen, Ib Jarle; Alpízar-Alpízar, Warner; Helgeland, Lars; Danø, Keld; Nielsen, Boye Schnack; Illemann, Martin

2012-08-01

Adenocarcinomas of lower oesophagus, gastro-oesophageal junction and cardia in humans are highly invasive tumours with poor prognosis. The localisation of urokinase-type plasminogen activator receptor (uPAR) was determined in 66 patients; 60 with adenocarcinomas and six cases with Barrett's oesophagus. uPAR was expressed in nearly all cases of invasive adenocarcinomas by populations of cancer cells, macrophages and myofibroblasts at both the invasion front and the tumour core. In areas with high-grade dysplasia or with Barrett's metaplasia adjacent to the tumour tissue, no uPAR-immunoreactivity was found. High local expression of uPAR, therefore, appears to be a characteristic marker for invasive behaviour in this tumour, suggesting that uPAR's contribution to matrix degradation during invasive growth is a late event in carcinogenesis. Using a scoring system for semiquantitative estimation of uPAR-positivity on immmunohistochemically stained specimens, a significant association was found between poor overall survival and high uPAR-score for cancer cells in the tumour core and for macrophages peripherally at the tumour invasion zone. In multivariate analysis, these two uPAR-scores were confirmed as highly significant prognostic parameters independent of Tumour, Node, Metastasis (TNM)-stage and World Health Organization (WHO) classification. The proteolytic action of these malignant and nonmalignant accessory cells thus seemed to follow two main patterns: one dominated by uPAR positive cancer cells and one by uPAR-positive macrophages. Scoring of uPAR-positivity might be a useful parameter for onset of invasion and prognosis in these adenocarcinomas. Copyright © 2011 UICC.

Centromere Binding and Evolution of Chromosomal Partition Systems in the Burkholderiales

PubMed Central

Passot, Fanny M.; Calderon, Virginie; Fichant, Gwennaele; Lane, David

2012-01-01

How split genomes arise and evolve in bacteria is poorly understood. Since each replicon of such genomes encodes a specific partition (Par) system, the evolution of Par systems could shed light on their evolution. The cystic fibrosis pathogen Burkholderia cenocepacia has three chromosomes (c1, c2, and c3) and one plasmid (pBC), whose compatibility depends on strictly specific interactions of the centromere sequences (parS) with their cognate binding proteins (ParB). However, the Par systems of B. cenocepacia c2, c3, and pBC share many features, suggesting that they arose within an extended family. Database searching revealed seven subfamilies of Par systems like those of B. cenocepacia. All are from plasmids and secondary chromosomes of the Burkholderiales, which reinforces the proposal of an extended family. The subfamily of the Par system of B. cenocepacia c3 includes plasmid variants with parS sequences divergent from that of c3. Using electrophoretic mobility shift assay (EMSA), we found that ParB-c3 binds specifically to centromeres of these variants, despite high DNA sequence divergence. We suggest that the Par system of B. cenocepacia c3 has preserved the features of an ancestral system. In contrast, these features have diverged variably in the plasmid descendants. One such descendant is found both in Ralstonia pickettii 12D, on a free plasmid, and in Ralstonia pickettii 12J, on a plasmid integrated into the main chromosome. These observations suggest that we are witnessing a plasmid-chromosome interaction from which a third chromosome will emerge in a two-chromosome species. PMID:22522899

Centromere binding and evolution of chromosomal partition systems in the Burkholderiales.

PubMed

Passot, Fanny M; Calderon, Virginie; Fichant, Gwennaele; Lane, David; Pasta, Franck

2012-07-01

How split genomes arise and evolve in bacteria is poorly understood. Since each replicon of such genomes encodes a specific partition (Par) system, the evolution of Par systems could shed light on their evolution. The cystic fibrosis pathogen Burkholderia cenocepacia has three chromosomes (c1, c2, and c3) and one plasmid (pBC), whose compatibility depends on strictly specific interactions of the centromere sequences (parS) with their cognate binding proteins (ParB). However, the Par systems of B. cenocepacia c2, c3, and pBC share many features, suggesting that they arose within an extended family. Database searching revealed seven subfamilies of Par systems like those of B. cenocepacia. All are from plasmids and secondary chromosomes of the Burkholderiales, which reinforces the proposal of an extended family. The subfamily of the Par system of B. cenocepacia c3 includes plasmid variants with parS sequences divergent from that of c3. Using electrophoretic mobility shift assay (EMSA), we found that ParB-c3 binds specifically to centromeres of these variants, despite high DNA sequence divergence. We suggest that the Par system of B. cenocepacia c3 has preserved the features of an ancestral system. In contrast, these features have diverged variably in the plasmid descendants. One such descendant is found both in Ralstonia pickettii 12D, on a free plasmid, and in Ralstonia pickettii 12J, on a plasmid integrated into the main chromosome. These observations suggest that we are witnessing a plasmid-chromosome interaction from which a third chromosome will emerge in a two-chromosome species.

Mesoscale variation in the photophysiology of the reef building coral Pocillopora damicornis along an environmental gradient

NASA Astrophysics Data System (ADS)

Cooper, Timothy F.; Ulstrup, Karin E.

2009-06-01

Spatial variation in the photophysiology of symbiotic dinoflagellates (zooxanthellae) of the scleractinian coral Pocillopora damicornis was examined along an environmental gradient in the Whitsunday Islands (Great Barrier Reef) at two depths (3 m and 6 m). Chlorophyll a fluorescence of photosystem II (PSII) and PAR-absorptivity measurements were conducted using an Imaging-PAM (pulse-amplitude-modulation) fluorometer. Most photophysiological parameters correlated with changes in environmental conditions quantified by differences in water quality along the gradient. For example, maximum quantum yield ( Fv/ Fm) increased and PAR-absorptivity decreased as water quality improved along the gradient from nearshore reefs (low irradiance, elevated nutrients and sediments) to outer islands (high irradiance, low nutrients and sediments). For apparent photosynthetic rate (PS max) and minimum saturating irradiance ( Ek), the direction of change differed depending on sampling depth, suggesting that different mechanisms of photo-acclimatisation operated between shallow and deep corals. Deep corals conformed to typical patterns of light/shade acclimatisation whereas shallow corals exhibited reduced PS max and Ek with improving water quality coinciding with greater heat dissipation (NPQ 241). Furthermore, deep corals on nearshore reefs exhibited elevated Q241 in comparison to outer islands possibly due to effects of sedimentation and/or pollutants rather than irradiance. These results highlight the importance of mesoscale sampling to obtain useful estimates of the variability of photophysiological parameters, particularly if such measures are to be used as bioindicators of the condition of coral reefs.

Doxycycline directly targets PAR1 to suppress tumor progression

PubMed Central

Qin, Yuan; Gu, Ju; Sun, Bo; Liu, Yanrong; Jing, Xiangyan; Hu, Xuejiao; Zhang, Peng; Zhou, Honggang; Sun, Tao; Yang, Cheng

2017-01-01

Doxycycline have been reported to exert anti-cancer activity and have been assessed as anti-cancer agents in clinical trials. However, the direct targets of doxycycline in cancer cells remain unclear. In this study, we used a chemical proteomics approach to identify the Protease-activated receptor 1 (PAR1) as a specific target of inhibition of doxycycline. Binding assays and single-molecule imaging assays were performed to confirm the inhibition of doxycycline to PAR1. The effect of doxycycline on multi-omics and cell functions were assessed based on a PAR1/thrombin model. Molecular docking and molecular dynamic simulations revealed that doxycycline interacts with key amino acids in PAR1. Mutation of PAR1 further confirmed the computation-based results. Moreover, doxycycline provides highly selective inhibition of PAR1 signaling in tumors in vitro and in vivo. Using pathological clinical samples co-stained for doxycycline and PAR1, it was found that doxycycline fluorescence intensity and PAR1 expression shown a clear positive correlation. Thus, doxycycline may be a useful targeted anti-cancer drug that should be further investigated in clinical trials. PMID:28187433

Doxycycline directly targets PAR1 to suppress tumor progression.

PubMed

Zhong, Weilong; Chen, Shuang; Zhang, Qiang; Xiao, Ting; Qin, Yuan; Gu, Ju; Sun, Bo; Liu, Yanrong; Jing, Xiangyan; Hu, Xuejiao; Zhang, Peng; Zhou, Honggang; Sun, Tao; Yang, Cheng

2017-03-07

Doxycycline have been reported to exert anti-cancer activity and have been assessed as anti-cancer agents in clinical trials. However, the direct targets of doxycycline in cancer cells remain unclear. In this study, we used a chemical proteomics approach to identify the Protease-activated receptor 1 (PAR1) as a specific target of inhibition of doxycycline. Binding assays and single-molecule imaging assays were performed to confirm the inhibition of doxycycline to PAR1. The effect of doxycycline on multi-omics and cell functions were assessed based on a PAR1/thrombin model. Molecular docking and molecular dynamic simulations revealed that doxycycline interacts with key amino acids in PAR1. Mutation of PAR1 further confirmed the computation-based results. Moreover, doxycycline provides highly selective inhibition of PAR1 signaling in tumors in vitro and in vivo. Using pathological clinical samples co-stained for doxycycline and PAR1, it was found that doxycycline fluorescence intensity and PAR1 expression shown a clear positive correlation. Thus, doxycycline may be a useful targeted anti-cancer drug that should be further investigated in clinical trials.

MtPAR MYB transcription factor acts as an on switch for proanthocyanidin biosynthesis in Medicago truncatula

PubMed Central

Verdier, Jerome; Zhao, Jian; Torres-Jerez, Ivone; Ge, Shujun; Liu, Chenggang; He, Xianzhi; Mysore, Kirankumar S.; Dixon, Richard A.; Udvardi, Michael K.

2012-01-01

MtPAR (Medicago truncatula proanthocyanidin regulator) is an MYB family transcription factor that functions as a key regulator of proanthocyanidin (PA) biosynthesis in the model legume Medicago truncatula. MtPAR expression is confined to the seed coat, the site of PA accumulation. Loss-of-function par mutants contained substantially less PA in the seed coat than the wild type, whereas levels of anthocyanin and other specialized metabolites were normal in the mutants. In contrast, massive accumulation of PAs occurred when MtPAR was expressed ectopically in transformed hairy roots of Medicago. Transcriptome analysis of par mutants and MtPAR-expressing hairy roots, coupled with yeast one-hybrid analysis, revealed that MtPAR positively regulates genes encoding enzymes of the flavonoid–PA pathway via a probable activation of WD40-1. Expression of MtPAR in the forage legume alfalfa (Medicago sativa) resulted in detectable levels of PA in shoots, highlighting the potential of this gene for biotechnological strategies to increase PAs in forage legumes for reduction of pasture bloat in ruminant animals. PMID:22307644

Photonic Switching Devices Using Light Bullets

NASA Technical Reports Server (NTRS)

Goorjian, Peter M. (Inventor)

1999-01-01

A unique ultra-fast, all-optical switching device or switch is made with readily available, relatively inexpensive, highly nonlinear optical materials. which includes highly nonlinear optical glasses, semiconductor crystals and/or multiple quantum well semiconductor materials. At the specified wavelengths. these optical materials have a sufficiently negative group velocity dispersion and high nonlinear index of refraction to support stable light bullets. The light bullets counter-propagate through, and interact within the waveguide to selectively change each others' directions of propagation into predetermined channels. In one embodiment, the switch utilizes a rectangularly planar slab waveguide. and further includes two central channels and a plurality of lateral channels for guiding the light bullets into and out of the waveguide. An advantage of the present all-optical switching device lies in its practical use of light bullets, thus preventing the degeneration of the pulses due to dispersion and diffraction at the front and back of the pulses. Another advantage of the switching device is the relative insensitivity of the collision process to the time difference in which the counter-propagating pulses enter the waveguide. since. contrary to conventional co-propagating spatial solitons, the relative phase of the colliding pulses does not affect the interaction of these pulses. Yet another feature of the present all-optical switching device is the selection of the light pulse parameters which enables the generation of light bullets in nonlinear optical materials. including highly nonlinear optical glasses and semiconductor materials such as semiconductor crystals and/or multiple quantum well semiconductor materials.

Effects of Kaolin Application on Light Absorption and Distribution, Radiation Use Efficiency and Photosynthesis of Almond and Walnut Canopies

PubMed Central

Rosati, Adolfo; Metcalf, Samuel G.; Buchner, Richard P.; Fulton, Allan E.; Lampinen, Bruce D.

2007-01-01

Background and Aims Kaolin applied as a suspension to plant canopies forms a film on leaves that increases reflection and reduces absorption of light. Photosynthesis of individual leaves is decreased while the photosynthesis of the whole canopy remains unaffected or even increases. This may result from a better distribution of light within the canopy following kaolin application, but this explanation has not been tested. The objective of this work was to study the effects of kaolin application on light distribution and absorption within tree canopies and, ultimately, on canopy photosynthesis and radiation use efficiency. Methods Photosynthetically active radiation (PAR) incident on individual leaves within the canopy of almond (Prunus dulcis) and walnut (Juglans regia) trees was measured before and after kaolin application in order to study PAR distribution within the canopy. The PAR incident on, and reflected and transmitted by, the canopy was measured on the same day for kaolin-sprayed and control trees in order to calculate canopy PAR absorption. These data were then used to model canopy photosynthesis and radiation use efficiency by a simple method proposed in previous work, based on the photosynthetic response to incident PAR of a top-canopy leaf. Key Results Kaolin increased incident PAR on surfaces of inner-canopy leaves, although there was an estimated 20 % loss in PAR reaching the photosynthetic apparatus, due to increased reflection. Assuming a 20 % loss of PAR, modelled photosynthesis and photosynthetic radiation use efficiency (PRUE) of kaolin-coated leaves decreased by only 6·3 %. This was due to (1) more beneficial PAR distribution within the kaolin-sprayed canopy, and (2) with decreasing PAR, leaf photosynthesis decreases less than proportionally, due to the curvature of the photosynthesis response-curve to PAR. The relatively small loss in canopy PRUE (per unit of incident PAR), coupled with the increased incident PAR on the leaf surface on inner-canopy leaves, resulted in an estimated increase in modelled photosynthesis of the canopy (+9 % in both walnut and almond). The small loss in PRUE (per unit of incident PAR) resulted in an increase in radiation use efficiency per unit of absorbed PAR, which more than compensated for the minor (7 %) reduction in canopy PAR absorption. Conclusions The results explain the apparently contradictory findings in the literature of positive or no effects of kaolin applications on canopy photosynthesis and yield, despite the decrease in photosynthesis by individual leaves when measured at the same PAR. PMID:17138580

Effects of kaolin application on light absorption and distribution, radiation use efficiency and photosynthesis of almond and walnut canopies.

PubMed

Rosati, Adolfo; Metcalf, Samuel G; Buchner, Richard P; Fulton, Allan E; Lampinen, Bruce D

2007-02-01

Kaolin applied as a suspension to plant canopies forms a film on leaves that increases reflection and reduces absorption of light. Photosynthesis of individual leaves is decreased while the photosynthesis of the whole canopy remains unaffected or even increases. This may result from a better distribution of light within the canopy following kaolin application, but this explanation has not been tested. The objective of this work was to study the effects of kaolin application on light distribution and absorption within tree canopies and, ultimately, on canopy photosynthesis and radiation use efficiency. Photosynthetically active radiation (PAR) incident on individual leaves within the canopy of almond (Prunus dulcis) and walnut (Juglans regia) trees was measured before and after kaolin application in order to study PAR distribution within the canopy. The PAR incident on, and reflected and transmitted by, the canopy was measured on the same day for kaolin-sprayed and control trees in order to calculate canopy PAR absorption. These data were then used to model canopy photosynthesis and radiation use efficiency by a simple method proposed in previous work, based on the photosynthetic response to incident PAR of a top-canopy leaf. Kaolin increased incident PAR on surfaces of inner-canopy leaves, although there was an estimated 20 % loss in PAR reaching the photosynthetic apparatus, due to increased reflection. Assuming a 20 % loss of PAR, modelled photosynthesis and photosynthetic radiation use efficiency (PRUE) of kaolin-coated leaves decreased by only 6.3 %. This was due to (1) more beneficial PAR distribution within the kaolin-sprayed canopy, and (2) with decreasing PAR, leaf photosynthesis decreases less than proportionally, due to the curvature of the photosynthesis response-curve to PAR. The relatively small loss in canopy PRUE (per unit of incident PAR), coupled with the increased incident PAR on the leaf surface on inner-canopy leaves, resulted in an estimated increase in modelled photosynthesis of the canopy (+9 % in both walnut and almond). The small loss in PRUE (per unit of incident PAR) resulted in an increase in radiation use efficiency per unit of absorbed PAR, which more than compensated for the minor (7 %) reduction in canopy PAR absorption. The results explain the apparently contradictory findings in the literature of positive or no effects of kaolin applications on canopy photosynthesis and yield, despite the decrease in photosynthesis by individual leaves when measured at the same PAR.

[Comprehensive testing system for cardiorespiratory interaction research].

PubMed

Zhang, Zhengbo; Wang, Buqing; Wang, Weidong; Zheng, Jiewen; Liu, Hongyun; Li, Kaiyuan; Sun, Congcong; Wang, Guojing

2013-04-01

To investigate the modulation effects of breathing movement on cardiovascular system and to study the physiological coupling relationship between respiration and cardiovascular system, we designed a comprehensive testing system for cardiorespiratory interaction research. This system, comprising three parts, i. e. physiological signal conditioning unit, data acquisition and USB medical isolation unit, and a PC based program, can acquire multiple physiological data such as respiratory flow, rib cage and abdomen movement, electrocardiograph, artery pulse wave, cardiac sounds, skin temperature, and electromyography simultaneously under certain experimental protocols. Furthermore this system can be used in research on short-term cardiovascular variability by paced breathing. Preliminary experiments showed that this system could accurately record rib cage and abdomen movement under very low breathing rate, using respiratory inductive plethysmography to acquire respiration signal in direct-current coupling mode. After calibration, this system can be used to estimate ventilation non-intrusively and correctly. The PC based program can generate audio and visual biofeedback signal, and guide the volunteers to perform a slow and regular breathing. An experiment on healthy volunteers showed that this system was able to guide the volunteers to do slow breathing effectively and simultaneously record multiple physiological data during the experiments. Signal processing techniques were used for off-line data analysis, such as non-invasive ventilation calibration, QRS complex wave detection, and respiratory sinus arrhythmia and pulse wave transit time calculation. The experiment result showed that the modulation effect on RR interval, respiratory sinus arrhythmia (RSA), pulse wave transit time (PWTT) by respiration would get stronger with the going of the slow and regular breathing.

Steering by hearing: a bat's acoustic gaze is linked to its flight motor output by a delayed, adaptive linear law.

PubMed

Ghose, Kaushik; Moss, Cynthia F

2006-02-08

Adaptive behaviors require sensorimotor computations that convert information represented initially in sensory coordinates to commands for action in motor coordinates. Fundamental to these computations is the relationship between the region of the environment sensed by the animal (gaze) and the animal's locomotor plan. Studies of visually guided animals have revealed an anticipatory relationship between gaze direction and the locomotor plan during target-directed locomotion. Here, we study an acoustically guided animal, an echolocating bat, and relate acoustic gaze (direction of the sonar beam) to flight planning as the bat searches for and intercepts insect prey. We show differences in the relationship between gaze and locomotion as the bat progresses through different phases of insect pursuit. We define acoustic gaze angle, theta(gaze), to be the angle between the sonar beam axis and the bat's flight path. We show that there is a strong linear linkage between acoustic gaze angle at time t [theta(gaze)(t)] and flight turn rate at time t + tau into the future [theta(flight) (t + tau)], which can be expressed by the formula theta(flight) (t + tau) = ktheta(gaze)(t). The gain, k, of this linkage depends on the bat's behavioral state, which is indexed by its sonar pulse rate. For high pulse rates, associated with insect attacking behavior, k is twice as high compared with low pulse rates, associated with searching behavior. We suggest that this adjustable linkage between acoustic gaze and motor output in a flying echolocating bat simplifies the transformation of auditory information to flight motor commands.

Noninvasive treatment of deep venous thrombosis using pulsed ultrasound cavitation therapy (histotripsy) in a porcine model.

PubMed

Maxwell, Adam D; Owens, Gabe; Gurm, Hitinder S; Ives, Kimberly; Myers, Daniel D; Xu, Zhen

2011-03-01

This study evaluated histotripsy as a noninvasive, image-guided method of thrombolysis in a porcine model of deep vein thrombosis. Histotripsy therapy uses short, high-intensity, focused ultrasound pulses to cause mechanical breakdown of targeted soft tissue by acoustic cavitation, which is guided by real-time ultrasound imaging. This is an in vivo feasibility study of histotripsy thrombolysis. Acute thrombi were formed in the femoral vein of juvenile pigs weighing 30-40 kg by balloon occlusion with two catheters and thrombin infusion. A 10-cm-diameter 1-MHz focused transducer was used for therapy. An 8-MHz ultrasound imager was used to align the clot with the therapy focus. Therapy consisted of five cycle pulses delivered at a rate of 1 kHz and peak negative pressure between 14 and 19 MPa. The focus was scanned along the long axis of the vessel to treat the entire visible clot during ultrasound exposure. The targeted region identified by a hyperechoic cavitation bubble cloud was visualized via ultrasound during treatment. Thrombus breakdown was apparent as a decrease in echogenicity within the vessel in 10 of 12 cases and in 7 cases improved flow through the vein as measured by color Doppler. Vessel histology found denudation of vascular endothelium and small pockets of hemorrhage in the vessel adventitia and underlying muscle and fatty tissue, but perforation of the vessel wall was never observed. The results indicate histotripsy has potential for development as a noninvasive treatment for deep vein thrombosis. Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.

Dishevelled-induced phosphorylation regulates membrane localization of Par1b

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

Terabayashi, Takeshi; Funato, Yosuke; Miki, Hiroaki, E-mail: hmiki@protein.osaka-u.ac.jp

2008-10-31

Par1b is an evolutionarily conserved kinase that plays crucial roles in cell polarity. Controlling intracellular localization of Par1b is important for its biological activity. We previously reported that Wnt stimulation or expression of Dvl promotes accumulation of Par1b in the membrane (T. Terabayashi, T.J. Itoh, H. Yamaguchi, Y. Yoshimura, Y. Funato, S. Ohno, H. Miki, Polarity-Regulating Kinase Partitioning-Defective 1/Microtubule Affinity-Regulating Kinase 2 Negatively Regulates Development of Dendrites on Hippocampal Neurons, J. Neurosci. 27 (2007) 13098-13107). However, its molecular mechanism remains unclear. Here we show the importance of Par1b phosphorylation in the regulation of membrane localization. We find that Thr-324 ismore » phosphorylated in a Dvl-dependent manner. Interestingly, the conversion of Thr-324 to Glu results in a significant accumulation of Par1b in the membrane, without any effects on the kinase activity. Moreover, the phospho-mimicking Par1b mutant does not antagonistically function against Dvl in microtubule stabilization and neurite extension, although wildtype Par1b does. These results suggest that membrane accumulation of Par1b induced by Dvl is regulated by its phosphorylation status, which is important for Par1b to regulate the microtubule dynamics.« less

Expression of protease-activated-receptor 2 (PAR-2) in human esophageal mucosa.

PubMed

Inci, Kamuran; Edebo, Anders; Olbe, Lars; Casselbrant, Anna

2009-01-01

The role of duodenal reflux in gastroesophageal reflux disease (GERD) containing bile salts and pancreatic enzymes (with special attention to trypsin) is still under discussion. Proteinase-activated receptors (PARs) are a novel family and PAR-2 is a unique member of this family because it is activated by trypsin. The aim of the present study was to examine the presence and the position of the PAR-2 receptor in human esophageal mucosa in different subgroups of GERD. Distal biopsies taken from healthy controls, patients with erosive reflux disease (ERD), patients with specialized intestinal metaplasia (SIM) and adenocarcinoma were analyzed for the PAR-2 receptor with reverse-transcription polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry. Gene transcripts for the PAR-2 receptor were found in all groups, with increased levels in SIM patients compared to controls. However, this visual pattern was not seen for the protein expression of the PAR-2 receptor showing no apparent quantitative differences between the groups. Immunohistochemistry revealed distinct staining for the PAR-2 receptor in the luminal part of the esophageal epithelium. The localization of the PAR-2 receptor indicates that the receptor can be cleaved and activated by trypsin in duodenogastric esophageal refluxate. The data thus suggest that the trypsin-PAR-2 pathway may be involved in the pathogenesis of GERD.

Transient early neurotrophin release and delayed inflammatory cytokine release by microglia in response to PAR-2 stimulation.

PubMed

Chen, Chen-Wen; Chen, Qian-Bo; Ouyang, Qing; Sun, Ji-Hu; Liu, Fang-Ting; Song, Dian-Wen; Yuan, Hong-Bin

2012-06-25

Activated microglia exerts both beneficial and deleterious effects on neurons, but the signaling mechanism controlling these distinct responses remain unclear. We demonstrated that treatment of microglial cultures with the PAR-2 agonist, 2-Furoyl-LIGRLO-NH2, evoked early transient release of BDNF, while sustained PAR-2 stimulation evoked the delayed release of inflammatory cytokines (IL-1 β and TNF-α) and nitric oxide. Culture medium harvested during the early phase (at 1 h) of microglial activation induced by 2-Furoyl-LIGRLO-NH2 (microglial conditioned medium, MCM) had no deleterious effects on cultured neurons, while MCM harvested during the late phase (at 72 h) promoted DNA fragmentation and apoptosis as indicated by TUNEL and annexin/PI staining. Blockade of PAR-1 during the early phase of PAR-2 stimulation enhanced BDNF release (by 11%, small but significant) while a PAR-1 agonist added during the late phase (24 h after 2-Furoyl-LIGRLO-NH2 addition) suppressed the release of cytokines and NO. The neuroprotective and neurotoxic effects of activated microglial exhibit distinct temporal profiles that are regulated by PAR-1 and PAR-2 stimulation. It may be possible to facilitate neuronal recovery and repair by appropriately timed stimulation and inhibition of microglial PAR-1 and PAR-2 receptors.

Mitogenic signaling of urokinase receptor-deficient kidney fibroblasts: actions of an alternative urokinase receptor and LDL receptor-related protein.

PubMed

Zhang, Guoqiang; Cai, Xiaohe; López-Guisa, Jesús M; Collins, Sarah J; Eddy, Allison A

2004-08-01

The urokinase receptor (uPAR) attenuates myofibroblast recruitment and fibrosis in the kidney. This study examined the role of uPAR and its co-receptor LDL receptor-related protein (LRP) in the regulation of kidney fibroblast proliferation and extracellular signal-regulated kinase (ERK) signaling. Compared with uPAR+/+ cells, uPAR-/- kidney fibroblasts were hyperproliferative. UPAR-/- fibroblast proliferation was 60% inhibited by an ERK kinase inhibitor. LRP protein was reduced and extracellular accumulation of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) proteins were greater in uPAR-/- cultures. Addition of functional uPA protein or LRP antisense RNA significantly increased ERK signaling and cell mitosis in both genotypes. Enhanced uPAR-/- fibroblast proliferation was reversed by a recombinant nonfunctional uPA peptide. The density of cell-bound fluor-uPA was similar between uPAR-/- and uPAR+/+ fibroblasts (78 +/- 6 versus 92 +/- 16 units). These data suggest that uPAR-deficient kidney fibroblasts express lower levels of its scavenger co-receptor LRP, resulting in greater extracellular accumulation of uPA and PAI-1. Enhanced proliferation of uPAR-/- fibroblasts seems to be mediated by uPA-dependent ERK signaling via an alternative urokinase receptor.

An enzyme-linked immunosorbent assay-based system for determining the physiological level of poly(ADP-ribose) in cultured cells.

PubMed

Ida, Chieri; Yamashita, Sachiko; Tsukada, Masaki; Sato, Teruaki; Eguchi, Takayuki; Tanaka, Masakazu; Ogata, Shin; Fujii, Takahiro; Nishi, Yoshisuke; Ikegami, Susumu; Moss, Joel; Miwa, Masanao

2016-02-01

PolyADP-ribosylation is mediated by poly(ADP-ribose) (PAR) polymerases (PARPs) and may be involved in various cellular events, including chromosomal stability, DNA repair, transcription, cell death, and differentiation. The physiological level of PAR is difficult to determine in intact cells because of the rapid synthesis of PAR by PARPs and the breakdown of PAR by PAR-degrading enzymes, including poly(ADP-ribose) glycohydrolase (PARG) and ADP-ribosylhydrolase 3. Artifactual synthesis and/or degradation of PAR likely occurs during lysis of cells in culture. We developed a sensitive enzyme-linked immunosorbent assay (ELISA) to measure the physiological levels of PAR in cultured cells. We immediately inactivated enzymes that catalyze the synthesis and degradation of PAR. We validated that trichloroacetic acid is suitable for inactivating PARPs, PARG, and other enzymes involved in metabolizing PAR in cultured cells during cell lysis. The PAR level in cells harvested with the standard radioimmunoprecipitation assay buffer was increased by 450-fold compared with trichloroacetic acid for lysis, presumably because of activation of PARPs by DNA damage that occurred during cell lysis. This ELISA can be used to analyze the biological functions of polyADP-ribosylation under various physiological conditions in cultured cells. Copyright © 2015 Elsevier Inc. All rights reserved.

Pulsed laser deposition of {CeO_2} and {Ce_{1-x}M_xO_2} (M = La, Zr): Application to insulating barrier in cuprate heterostructures

NASA Astrophysics Data System (ADS)

Berger, S.; Contour, J.-P.; Drouet, M.; Durand, O.; Khodan, A.; Michel, D.; Régi, F.-X.

1998-03-01

SrTiO_3 had been often tentatively used as an insulating barrier for HT superconductor/insulator heterostructures. Unfortunately, the deposition of SrTiO_3 on the YBa_2Cu_3O_7 inverse interface results in a poor epitaxial regrowth producing a high roughness dislocated titanate layer. Taking into account the good matching with YBa_2Cu_3O_7 and LaAlO_3, CeO_2 and Ce_{1-x}M_xO_2 (M = La, Zr), epitaxial layers were grown by pulsed laser deposition on LaAlO_3 substrates and introduced into YBa_2Cu_3O_7 based heterostructures as insulating barrier. After adjusting the growth parameters from RHEED oscillations, epitaxial growth is achieved, the oxide crystal axes being rotated by 45^circ from those of the substrate. The surface roughness of 250 nm thick films is very low with a rms value lower than 0.5 nm over 1;μ m^2. The YBa_2Cu_3O_7 layers of a YBa_2Cu_3O_7/CeO_2 /YBa_2Cu_3O_7 heterostructures grown using these optimized parameters show an independent resistive transition, when the thickness is larger than 25 nm, respectively at T_c_1 = 89.6;K and T_c_2 = 91.4;{K}. SrTiO3 est souvent utilisé comme barrière isolante dans des hétérostructures SIS de cuprates supraconducteurs, cependant les défauts générés lors de la croissance de ce titanate sur l'interface inverse de YBa2Cu3O7 conduisent à un matériau dont la qualité cristalline et les propriétés physiques sont médiocres. L'oxyde de cérium CeO2 est également une barrière isolante potentielle intéressante pour ces structures SIS basées sur YBa2Cu3O7 car cet oxyde cubique (a = 0,5411 nm, asqrt{2}/2 = 0,3825 nm) qui est peu désaccordé par rapport au plan ab du cuprate (Δ a/a = - 0,18 %, Δ b/a = 1,6 %) présente de plus un coefficient de dilatation thermique (10,6 × 10^{-6 circ}C^{-1}) très voisin de celui de YBa2Cu3O7 (13 × 10^{-6 circ}C^{-1}). Nous avons donc étudié l'épitaxie de CeO2 et des oxydes de type Ce{1-x}MxO2 (M = La, Zr) en ablation laser pulsée afin de définir des conditions de croissance optimisées pour la réalisation de barrières isolantes ultra-minces à faible rugosité d'interface. L'interface de croissance a été caractérisée par analyse en diffraction d'électrons rapides en incidence rasante (RHEED) en temps réel et par analyse ex-situ en microscopie par force atomique (AFM) et diffraction de rayons X (DRX). Lorsque les paramètres de la croissance (T, p_O_2, fréquence du laser, distance cible-substrat...) sont optimisés par observation des oscillations d'intensité de RHEED, les films sont épitaxiés à 45^{circ} des axes du substrat. La rugosité rms d'un film de 250 nm d'épaisseur déterminée par AFM sur 1 μ m^2 est alors inférieure à 0,5 nm, c'est-à-dire de l'ordre de la hauteur d'une maille élémentaire. Ces conditions optimisées ont été utilisées pour la réalisation d'hétérostructures YBa2Cu3O7/CeO2/YBa2Cu3O7, lorsque l'épaisseur est supérieure à 25 nm, les couches élémentaires de YBa2Cu3O7 présentent des transitions résistive indépendantes respectivement à T_c_1 = 89,6 K et T_c_2 = 91,4 K.

Ultrasound guided electrochemotherapy for the treatment of a clear cell thymoma in a cat

PubMed Central

Spugnini, Enrico Pierluigi; Menicagli, Francesco; Pettorali, Michela; Baldi, Alfonso

2017-01-01

A twelve-year-old male castrated domestic shorthair cat was presented for rapidly progressing respiratory distress. The cat was depressed, tachypneic and moderately responsive. Ultrasonography showed a mediastinal mass associated with a significant pleural effusion that needed tapping every five to seven days. Ultrasound guided biopsy yielded a diagnosis of clear cell thymoma upon histopathology. After complete staging procedures, the owner elected to treat the cat with electrochemotherapy (ECT) using systemic bleomycin. Two sessions of ultrasound guided ECT were performed at two week intervals with trains of biphasic electric pulses applied using needle electrodes until complete coverage of the area was achieved. The treatment was well tolerated and resulted in partial remission (PR). Additional sessions were performed on a monthly basis. The cat is still in PR after fourteen months. ECT resulted in improved local control and should be considered among the available adjuvant treatments in pets carrying visceral tumors. PMID:28331834

Guided-wave phase-matched second-harmonic generation in KTiOPO4 waveguide produced by swift heavy-ion irradiation

NASA Astrophysics Data System (ADS)

Cheng, Yazhou; Jia, Yuechen; Akhmadaliev, Shavkat; Zhou, Shengqiang; Chen, Feng

2014-11-01

We report on the guided-wave second-harmonic generation in a KTiOPO4 nonlinear optical waveguide fabricated by a 17 MeV O5+ ion irradiation at a fluence of 1.5×1015 ions/cm2. The waveguide guides light along both TE and TM polarizations, which is suitable for phase-matching frequency doubling. Second harmonics of green light at a wavelength of 532 nm have been generated through the KTiOPO4 waveguide platform under an optical pump of fundamental wave at 1064 nm in both continuous-wave and pulsed regimes, reaching optical conversion efficiencies of 5.36%/W and 11.5%, respectively. The propagation losses have been determined to be ˜3.1 and ˜5.7 dB/cm for the TE and TM polarizations at a wavelength of 632.8 nm, respectively.

The intracellular carboxyl tail of the PAR-2 receptor controls intracellular signaling and cell death.

PubMed

Zhu, Zhihui; Stricker, Rolf; Li, Rong yu; Zündorf, Gregor; Reiser, Georg

2015-03-01

The protease-activated receptors are a group of unique G protein-coupled receptors, including PAR-1, PAR-2, PAR-3 and PAR-4. PAR-2 is activated by multiple trypsin-like serine proteases, including trypsin, tryptase and coagulation proteases. The clusters of phosphorylation sites in the PAR-2 carboxyl tail are suggested to be important for the binding of adaptor proteins to initiate intracellular signaling to Ca(2+) and mitogen-activated protein kinases. To explore the functional role of PAR-2 carboxyl tail in controlling intracellular Ca(2+), ERK and AKT signaling, a series of truncated mutants containing different clusters of serines/threonines were generated and expressed in HEK293 cells. Firstly, we observed that lack of the complete C-terminus of PAR-2 in a mutated receptor gave a relatively low level of localization on the cell plasma membrane. Secondly, the shortened carboxyl tail containing 13 amino acids was sufficient for receptor internalization. Thirdly, the cells expressing truncation mutants showed deficits in their capacity to couple to intracellular Ca(2+) and ERK and AKT signaling upon trypsin challenge. In addition, HEK293 cells carrying different PAR-2 truncation mutants displayed decreased levels of cell survival after long-lasting trypsin stimulation. In summary, the PAR-2 carboxyl tail was found to control the receptor localization, internalization, intracellular Ca(2+) responses and signaling to ERK and AKT. The latter can be considered to be important for cell death control.

PAR-2 expression in the gingival crevicular fluid reflects chronic periodontitis severity.

PubMed

Fukushima, Henrique; Alves, Vanessa Tubero Euzebio; Carvalho, Verônica Franco de; Ambrósio, Lucas Macedo Batitucci; Eichler, Rosangela Aparecida Dos Santos; Carvalho, Maria Helena Catelli de; Saraiva, Luciana; Holzhausen, Marinella

2017-01-26

Recent studies investigating protease-activated receptor type 2 (PAR-2) suggest an association between the receptor and periodontal inflammation. It is known that gingipain, a bacterial protease secreted by the important periodontopathogen Porphyromonas gingivalis can activate PAR-2. Previous studies by our group found that PAR-2 is overexpressed in the gingival crevicular fluid (GCF) of patients with moderate chronic periodontitis (MP). The present study aimed at evaluating whether PAR-2 expression is associated with chronic periodontitis severity. GCF samples and clinical parameters, including plaque and bleeding on probing indices, probing pocket depth and clinical attachment level, were collected from the control group (n = 19) at baseline, and from MP patients (n = 19) and severe chronic periodontitis (SP) (n = 19) patients before and 6 weeks after periodontal non-surgical treatment. PAR-2 and gingipain messenger RNA (mRNA) in the GCF of 4 periodontal sites per patient were evaluated by Reverse Transcription Polymerase Chain Reaction (RT-qPCR). PAR-2 and gingipain expressions were greater in periodontitis patients than in control group patients. In addition, the SP group presented increased PAR-2 and gingipain mRNA levels, compared with the MP group. Furthermore, periodontal treatment significantly reduced (p <0.05) PAR-2 expression in patients with periodontitis. In conclusion, PAR-2 is associated with chronic periodontitis severity and with gingipain levels in the periodontal pocket, thus suggesting that PAR-2 expression in the GCF reflects the severity of destruction during periodontal infection.

Effect of Par Frying on Composition and Texture of Breaded and Battered Catfish

PubMed Central

Woods, Kristin; Lea, Jeanne M.; Brashear, Suzanne S.; Boue, Stephen M.; Daigle, Kim W.; Bett-Garber, Karen L.

2018-01-01

Catfish is often consumed as a breaded and battered fried product; however, there is increasing interest in breaded and battered baked products as a healthier alternative. Par frying can improve the texture properties of breaded and battered baked products, but there are concerns about the increase in lipid uptake from par frying. The objective of this study was to examine the effect of different batters (rice, corn, and wheat) and the effect of par frying on the composition and texture properties of baked catfish. Catfish fillets were cut strips and then coated with batters, which had similar viscosities. Half of the strips were par fried in 177 °C vegetable oil for 1 min and the other half were not par fried. Samples were baked at 177 °C for 25 min. Analysis included % batter adhesion, cooking loss, protein, lipid, ash, and moisture, plus hardness and fracture quality measured using a texture analyzer. A trained sensory panel evaluated both breading and flesh texture attributes. Results found the lipid content of par fried treatments were significantly higher for both corn and wheat batters than for non-par fried treatments. Sensory analysis indicated that the texture of the coatings in the par fried treatments were significantly greater for hardness attributes. Fillet flakiness was significantly greater in the par fried treatments and corn-based batters had moister fillet strips compared to the wheat flour batters. Texture analyzer hardness values were higher for the par fried treatments. PMID:29570660

Combination with CK19 Might Increase the Prognostic Power of Hep Par 1 in Hepatocellular Carcinoma after Curative Resection.

PubMed

Jin, Ye; Liang, Zhi-Yong; Zhou, Wei-Xun; Zhou, Li

2017-07-31

Hepatocyte Paraffin 1 (Hep Par 1) and cytokeratin 19 (CK19) were shown to be associated with post-surgical prognosis of hepatocellular carcinoma (HCC). However, further validation might be needed. Besides, their combined evaluation has not been reported. The present study was designed to address the issues. Expressions of Hep Par 1 and CK19 were detected using tissue microarray-based immunohistochemical staining in 79 patients with HCC underwent curative hepatectomy. Their associations with cliniopathologic variables, overall and recurrence-free survival were analyzed. Hep Par 1 was highly expressed in 61 patients (77.2%), whereas CK19 was positive in 8 patients (10.1%). Moreover, expressions of these two proteins were all associated with tumor-node-metastasis (TNM) stage and vascular invasion. It was found that high Hep Par 1 expression was univariately associated with good overall and recurrence-free survival, while CK19 was marginally prognostic. Also in univariate analyses, combination of the two markers more effectively predicted for long-term prognosis in HCC than Hep Par 1 did. However, neither Hep Par 1 nor Hep Par 1/CK19 was multivariately significant. Finally, Hep Par 1/CK19 combined with TNM stage might obtain more satisfactory outcome prediction, especially for overall survival. Combination of CK19 with Hep Par 1 might have higher prognostic power, which might be further improved by adding TNM stage, than Hep Par 1 alone, in resected HCC. Of course, subsequent confirmation is necessary.

Par-4, a Gene Required for Cytoplasmic Localization and Determination of Specific Cell Types in Caenorhabditis Elegans Embryogenesis

PubMed Central

Morton, D. G.; Roos, J. M.; Kemphues, K. J.

1992-01-01

Specification of some cell fates in the early Caenorhabditis elegans embryo is mediated by cytoplasmic localization under control of the maternal genome. Using nine newly isolated mutations, and two existing mutations, we have analyzed the role of the maternally expressed gene par-4 in cytoplasmic localization. We recovered seven new par-4 alleles in screens for maternal effect lethal mutations that result in failure to differentiate intestinal cells. Two additional par-4 mutations were identified in noncomplementation screens using strains with a high frequency of transposon mobility. All 11 mutations cause defects early in development of embryos produced by homozygous mutant mothers. Analysis with a deficiency in the region indicates that it33 is a strong loss-of-function mutation. par-4(it33) terminal stage embryos contain many cells, but show no morphogenesis, and are lacking intestinal cells. Temperature shifts with the it57ts allele suggest that the critical period for both intestinal differentiation and embryo viability begins during oogenesis, about 1.5 hr before fertilization, and ends before the four-cell stage. We propose that the primary function of the par-4 gene is to act as part of a maternally encoded system for cytoplasmic localization in the first cell cycle, with par-4 playing a particularly important role in the determination of intestine. Analysis of a par-4;par-2 double mutant suggests that par-4 and par-2 gene products interact in this system. PMID:1582558

Direct experimental observation of the gas density depression effect using a two-bunch X-ray FEL beam.

PubMed

Feng, Y; Schafer, D W; Song, S; Sun, Y; Zhu, D; Krzywinski, J; Robert, A; Wu, J; Decker, F J

2018-01-01

The experimental observation of the depression effect in gas devices designed for X-ray free-electron lasers (FELs) is reported. The measurements were carried out at the Linac Coherent Light Source using a two-bunch FEL beam at 6.5 keV with 122.5 ns separation passing through an argon gas cell. The relative intensities of the two pulses of the two-bunch beam were measured, after and before the gas cell, from X-ray scattering off thin targets by using fast diodes with sufficient temporal resolution. At a cell pressure of 140 hPa, it was found that the after-to-before ratio of the intensities of the second pulse was about 17% ± 6% higher than that of the first pulse, revealing lower effective attenuation of the gas cell due to heating by the first pulse and subsequent gas density reduction in the beam path. This measurement is important in guiding the design and/or mitigating the adverse effects in gas devices for high-repetition-rate FELs such as the LCLS-II and the European XFEL or other future high-repetition-rate upgrades to existing FEL facilities.

Direct experimental observation of the gas density depression effect using a two-bunch X-ray FEL beam

DOE PAGES

Feng, Y.; Schafer, D. W.; Song, S.; ...

2018-01-01

The experimental observation of the depression effect in gas devices designed for X-ray free-electron lasers (FELs) is reported. The measurements were carried out at the Linac Coherent Light Source using a two-bunch FEL beam at 6.5 keV with 122.5 ns separation passing through an argon gas cell. The relative intensities of the two pulses of the two-bunch beam were measured, after and before the gas cell, from X-ray scattering off thin targets by using fast diodes with sufficient temporal resolution. At a cell pressure of 140 hPa, it was found that the after-to-before ratio of the intensities of the secondmore » pulse was about 17% ± 6% higher than that of the first pulse, revealing lower effective attenuation of the gas cell due to heating by the first pulse and subsequent gas density reduction in the beam path. Furthermore, this measurement is important in guiding the design and/or mitigating the adverse effects in gas devices for high-repetition-rate FELs such as the LCLS-II and the European XFEL or other future high-repetition-rate upgrades to existing FEL facilities.« less

Direct experimental observation of the gas density depression effect using a two-bunch X-ray FEL beam

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

Feng, Y.; Schafer, D. W.; Song, S.

The experimental observation of the depression effect in gas devices designed for X-ray free-electron lasers (FELs) is reported. The measurements were carried out at the Linac Coherent Light Source using a two-bunch FEL beam at 6.5 keV with 122.5 ns separation passing through an argon gas cell. The relative intensities of the two pulses of the two-bunch beam were measured, after and before the gas cell, from X-ray scattering off thin targets by using fast diodes with sufficient temporal resolution. At a cell pressure of 140 hPa, it was found that the after-to-before ratio of the intensities of the secondmore » pulse was about 17% ± 6% higher than that of the first pulse, revealing lower effective attenuation of the gas cell due to heating by the first pulse and subsequent gas density reduction in the beam path. Furthermore, this measurement is important in guiding the design and/or mitigating the adverse effects in gas devices for high-repetition-rate FELs such as the LCLS-II and the European XFEL or other future high-repetition-rate upgrades to existing FEL facilities.« less

Extracting the distribution of laser damage precursors on fused silica surfaces for 351 nm, 3 ns laser pulses at high fluences (20-150 J/cm2).

PubMed

Laurence, Ted A; Bude, Jeff D; Ly, Sonny; Shen, Nan; Feit, Michael D

2012-05-07

Surface laser damage limits the lifetime of optics for systems guiding high fluence pulses, particularly damage in silica optics used for inertial confinement fusion-class lasers (nanosecond-scale high energy pulses at 355 nm/3.5 eV). The density of damage precursors at low fluence has been measured using large beams (1-3 cm); higher fluences cannot be measured easily since the high density of resulting damage initiation sites results in clustering. We developed automated experiments and analysis that allow us to damage test thousands of sites with small beams (10-30 µm), and automatically image the test sites to determine if laser damage occurred. We developed an analysis method that provides a rigorous connection between these small beam damage test results of damage probability versus laser pulse energy and the large beam damage results of damage precursor densities versus fluence. We find that for uncoated and coated fused silica samples, the distribution of precursors nearly flattens at very high fluences, up to 150 J/cm2, providing important constraints on the physical distribution and nature of these precursors.

Pulse transit time reveals drug kinetics on vascular changes affected by propofol.

PubMed

Lan, Yuan-Chun; Shen, Ching-Hui; Kang, Hsung-Ming; Chong, Fok-Ching

2012-01-01

Pulse transit time (PTT) is the duration in which a pulse wave travels between two arterial sites within the same cardiac cycle. The aim of our study is to use PTT to examine propofol's effects on the vascular system. Methods. We collected data from 50 healthy women, between 28 and 51 years old, who underwent gynaecological surgery under general anaesthesia. The general anaesthesia was induced with propofol injection (2 mg/kg). PTT measurements were obtained from the R-wave of electrocardiogram and the pulse wave of photoplethysmograph. Two PTT values were obtained; one before (the control) and the other after propofol injection. The results were analysed by Student's t-test. Results. After propofol injection, the PTT was prolonged. The change in the PTT value from that of baseline was significant statistically (P < 0.05, by Student's t-test). The PTT change over time correlated with the degree of vasodilatation over time. Monitoring of PTT not only revealed the magnitude of vascular changes but also demonstrated the onset of vascular dilation, its peak and duration. We conclude that PTT is a useful guide in monitoring the drug kinetics of propofol.

Performance of laser guide star adaptive optics at Lick Observatory

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

Olivier, S.S.; An, J.; Avicola, K.

1995-07-19

A sodium-layer laser guide star adaptive optics system has been developed at Lawrence Livermore National Laboratory (LLNL) for use on the 3-meter Shane telescope at Lick Observatory. The system is based on a 127-actuator continuous-surface deformable mirror, a Hartmann wavefront sensor equipped with a fast-framing low-noise CCD camera, and a pulsed solid-state-pumped dye laser tuned to the atomic sodium resonance line at 589 nm. The adaptive optics system has been tested on the Shane telescope using natural reference stars yielding up to a factor of 12 increase in image peak intensity and a factor of 6.5 reduction in image fullmore » width at half maximum (FWHM). The results are consistent with theoretical expectations. The laser guide star system has been installed and operated on the Shane telescope yielding a beam with 22 W average power at 589 nm. Based on experimental data, this laser should generate an 8th magnitude guide star at this site, and the integrated laser guide star adaptive optics system should produce images with Strehl ratios of 0.4 at 2.2 {mu}m in median seeing and 0.7 at 2.2 {mu}m in good seeing.« less

Focusing electrode and coaxial reflector used for reducing the guiding magnetic field of the Ku-band foilless transit-time oscillator

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

Ling, Junpu; Zhang, Jiande; He, Juntao, E-mail: hejuntao12@163.com

2014-08-15

Based on the theoretical analysis of the intense relativistic electron beam propagation in the coaxial drift-tube, a focusing electrode and a coaxial reflector is proposed to lessen the demand of the coaxial Ku-band foilless transit-time oscillator (TTO) for the guiding magnetic field. Moreover, a Ku-band TTO with the focusing electrode and the coaxial reflector is designed and studied by particle in cell simulation. When the diode voltage is 390 kV, the beam current 7.8 kA, and the guiding magnetic field is only 0.3 T, the device can output 820 MW microwave pulse at 14.25 GHz by means of the simulation.more » However, for the device without them, the output power is only 320 MW. The primary experiments are also carried out. When the guiding magnetic field is 0.3 T, the output power of the device with the focusing electrode and the coaxial reflector is double that of the one without them. The simulation and experimental results prove that the focusing electrode and the coaxial reflector are effective on reducing the guiding magnetic field of the device.« less

Test-retest reliability of pulse amplitude tonometry measures of vascular endothelial function: implications for clinical trial design.

PubMed

McCrea, Cindy E; Skulas-Ray, Ann C; Chow, Mosuk; West, Sheila G

2012-02-01

Endothelial dysfunction is an important outcome for assessing vascular health in intervention studies. However, reliability of the standard non-invasive method (flow-mediated dilation) is a significant challenge for clinical applications and multicenter trials. We evaluated the repeatability of pulse amplitude tonometry (PAT) to measure change in pulse wave amplitude during reactive hyperemia (Itamar Medical Ltd, Caesarea, Israel). Twenty healthy adults completed two PAT tests (mean interval = 19.5 days) under standardized conditions. PAT-derived measures of endothelial function (reactive hyperemia index, RHI) and arterial stiffness (augmentation index, AI) showed strong repeatability (intra-class correlations = 0.74 and 0.83, respectively). To guide future research, we also analyzed sample size requirements for a range of effect sizes. A crossover design powered at 0.90 requires 28 participants to detect a 15% change in RHI. Our study is the first to show that PAT measurements are repeatable in adults over an interval greater than 1 week.

Resonant Pump-dump Quantum Control of Solvated Dye Molecules with Phase Jumps

NASA Astrophysics Data System (ADS)

Konar, Arkaprabha; Lozovoy, Vadim; Dantus, Marcos

2014-03-01

Quantum coherent control of two photon and multiphoton excitation processes in atomic and condensed phase systems employing phase jumps has been well studied and understood. Here we demonstrate coherent quantum control of a two photon resonant pump-dump process in a complex solvated dye molecule. Phase jump in the frequency domain via a pulse shaper is employed to coherently enhance the stimulated emission by an order of magnitude when compared to transform limited pulses. Red shifted stimulated emission from successive low energy Stokes shifted excited states leading to narrowband emission are observed upon scanning the pi step across the excitation spectrum. A binary search space routine was also employed to investigate the effects of other types of phase jumps on stimulated emission and to determine the optimum phase that maximizes the emission. Understanding the underlying mechanism of this kind of enhancement will guide us in designing pulse shapes for enhancing stimulated emission, which can be further applied in the field of imaging.

Single-photon imager based on a superconducting nanowire delay line

NASA Astrophysics Data System (ADS)

Zhao, Qing-Yuan; Zhu, Di; Calandri, Niccolò; Dane, Andrew E.; McCaughan, Adam N.; Bellei, Francesco; Wang, Hao-Zhu; Santavicca, Daniel F.; Berggren, Karl K.

2017-03-01

Detecting spatial and temporal information of individual photons is critical to applications in spectroscopy, communication, biological imaging, astronomical observation and quantum-information processing. Here we demonstrate a scalable single-photon imager using a single continuous superconducting nanowire that is not only a single-photon detector but also functions as an efficient microwave delay line. In this context, photon-detection pulses are guided in the nanowire and enable the readout of the position and time of photon-absorption events from the arrival times of the detection pulses at the nanowire's two ends. Experimentally, we slowed down the velocity of pulse propagation to ∼2% of the speed of light in free space. In a 19.7 mm long nanowire that meandered across an area of 286 × 193 μm2, we were able to resolve ∼590 effective pixels with a temporal resolution of 50 ps (full width at half maximum). The nanowire imager presents a scalable approach for high-resolution photon imaging in space and time.

Increased Protease-Activated Receptor-2 (PAR-2) Expression on CD14++CD16+ Peripheral Blood Monocytes of Patients with Severe Asthma

PubMed Central

Shrestha Palikhe, Nami; Nahirney, Drew; Laratta, Cheryl; Gandhi, Vivek Dipak; Vethanayagam, Dilini; Bhutani, Mohit; Mayers, Irvin

2015-01-01

Background Protease-Activated Receptor-2 (PAR-2), a G protein coupled receptor activated by serine proteases, is widely expressed in humans and is involved in inflammation. PAR-2 activation in the airways plays an important role in the development of allergic airway inflammation. PAR-2 expression is known to be upregulated in the epithelium of asthmatic subjects, but its expression on immune and inflammatory cells in patients with asthma has not been studied. Methods We recruited 12 severe and 24 mild/moderate asthmatics from the University of Alberta Hospital Asthma Clinics and collected baseline demographic information, medication use and parameters of asthma severity. PAR-2 expression on blood inflammatory cells was analyzed by flow cytometry. Results Subjects with severe asthma had higher PAR-2 expression on CD14++CD16+ monocytes (intermediate monocytes) and also higher percentage of CD14++CD16+PAR-2+ monocytes (intermediate monocytes expressing PAR-2) in blood compared to subjects with mild/moderate asthma. Receiver operating characteristics (ROC) curve analysis showed that the percent of CD14++CD16+PAR-2+ in peripheral blood was able to discriminate between patients with severe and those with mild/moderate asthma with high sensitivity and specificity. In addition, among the whole populations, subjects with a history of asthma exacerbations over the last year had higher percent of CD14++CD16+ PAR-2+ cells in peripheral blood compared to subjects without exacerbations. Conclusions PAR-2 expression is increased on CD14++CD16+ monocytes in the peripheral blood of subjects with severe asthma and may be a biomarker of asthma severity. Our data suggest that PAR-2 -mediated activation of CD14++CD16+ monocytes may play a role in the pathogenesis of severe asthma. PMID:26658828

Control of cleavage spindle orientation in Caenorhabditis elegans: The role of the genes par-2 and par-3

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

Cheng, N.N.; Kirby, C.M.; Kemphues, K.J.

1995-02-01

Polarized asymmetric divisions play important roles in the development of plants and animals. The first two embryonic cleavages of Caenorhabditis elegans provide an opportunity to study the mechanisms controlling polarized asymmetric divisions. The first cleavage is unequal, producing daughters with different sizes and fates. The daughter blastomeres divide with different orientations at the second cleavage; the anterior blastomere divides equally across the long axis of the egg, whereas the posterior blastomere divides unequally along the long axis. We report here the results of our analysis of the genes par-2 and par-3 with respect to their contribution to the polarity ofmore » these divisions. Strong loss-of-function mutations in both genes lead to an equal first cleavage and an altered second cleavage. Interestingly, the mutations exhibit striking gene-specific differences at the second cleavage. The par-2 mutations lead to transverse spindle orientations in both blastomeres, whereas par-3 mutations lead to longitudinal spindle orientations in both blastomeres. The spindle orientation defects correlate with defects in centrosome movements during both the first and the second cell cycle. Temperature shift experiments with par-2 (it5ts) indicate that the par-2(+) activity is not required after the two-cell stage. Analysis of double mutants shows that par-3 is epistatic to par-2. We propose a model wherein par-2(+) and par-3(+) act in concert during the first cell cycle to affect asymmetric modification of the cytoskeleton. This polar modification leads to different behaviors of centrosomes in the anterior and posterior and leads ultimately to blastomere-specific spindle orientations at the second cleavage. 44 refs., 5 figs., 5 tabs.« less

Increased Protease-Activated Receptor-2 (PAR-2) Expression on CD14++CD16+ Peripheral Blood Monocytes of Patients with Severe Asthma.

PubMed

Shrestha Palikhe, Nami; Nahirney, Drew; Laratta, Cheryl; Gandhi, Vivek Dipak; Vethanayagam, Dilini; Bhutani, Mohit; Mayers, Irvin; Cameron, Lisa; Vliagoftis, Harissios

2015-01-01

Protease-Activated Receptor-2 (PAR-2), a G protein coupled receptor activated by serine proteases, is widely expressed in humans and is involved in inflammation. PAR-2 activation in the airways plays an important role in the development of allergic airway inflammation. PAR-2 expression is known to be upregulated in the epithelium of asthmatic subjects, but its expression on immune and inflammatory cells in patients with asthma has not been studied. We recruited 12 severe and 24 mild/moderate asthmatics from the University of Alberta Hospital Asthma Clinics and collected baseline demographic information, medication use and parameters of asthma severity. PAR-2 expression on blood inflammatory cells was analyzed by flow cytometry. Subjects with severe asthma had higher PAR-2 expression on CD14++CD16+ monocytes (intermediate monocytes) and also higher percentage of CD14++CD16+PAR-2+ monocytes (intermediate monocytes expressing PAR-2) in blood compared to subjects with mild/moderate asthma. Receiver operating characteristics (ROC) curve analysis showed that the percent of CD14++CD16+PAR-2+ in peripheral blood was able to discriminate between patients with severe and those with mild/moderate asthma with high sensitivity and specificity. In addition, among the whole populations, subjects with a history of asthma exacerbations over the last year had higher percent of CD14++CD16+ PAR-2+ cells in peripheral blood compared to subjects without exacerbations. PAR-2 expression is increased on CD14++CD16+ monocytes in the peripheral blood of subjects with severe asthma and may be a biomarker of asthma severity. Our data suggest that PAR-2 -mediated activation of CD14++CD16+ monocytes may play a role in the pathogenesis of severe asthma.

The role of proteinase 3 (PR3) and the protease-activated receptor-2 (PAR-2) pathway in dendritic cell (DC) maturation of human-DC-like monocytes and murine DC.

PubMed

Jiang, Bo; Grage-Griebenow, Evelin; Csernok, Elena; Butherus, Kristine; Ehlers, Stefan; Gross, Wolfgang L; Holle, Julia U

2010-01-01

The aim of the study was to assess PAR-2 expression on dendritic cell (DC) subsets and other immune cells of Wegener's granulomatosis (WG) patients and healthy controls (HC) and to investigate whether Proteinase 3 (PR3, a serine protease which can activate PAR2) induces maturation of human DC-like monocytes and murine Flt-3 ligand- and GM-CSF-generated DC. Human peripheral blood cells including DC subsets and Flt-3l- and GM-CSF-generated mouse DC were analysed for expression of PAR-2 and DC maturation markers by flow cytometry before and after stimulation with PR3, trypsin, PAR-2 agonist or LPS for 24 h. There was no difference of PAR-2 expression on PMNs, monocytes, lymphocytes and DC between all WG samples and HC. However, in inactive WG, expression of PAR-2 was downregulated on the cell surface of PMNs, monocytes, lymphocytes, and CD11c+DC compared to active WG and HC. PR3 and PAR2-agonists did not induce upregulation of PAR-2 or maturation markers of human DC-like monocytes in WG and HC. Likewise, murine PR3 did not induce upregulation of PAR-2 or maturation markers in murine DC. PAR-2 expression is downregulated on human peripheral blood cells including CD11c+ DC in inactive WG compared to active WG and HC, possibly reflecting a non-activated status of these cells in inactive disease. PR3 and PAR-2- agonists did not induce maturation of human ex vivo DC-like monocytes in WG and HC and of murine DC, suggesting this pathway is not singularly involved in the maturation of these cell subsets.

Protease-Activated Receptor 2 Activation Inhibits N-Type Ca2+ Currents in Rat Peripheral Sympathetic Neurons

PubMed Central

Kim, Young-Hwan; Ahn, Duck-Sun; Kim, Myeong Ok; Joeng, Ji-Hyun; Chung, Seungsoo

2014-01-01

The protease-activated receptor (PAR)-2 is highly expressed in endothelial cells and vascular smooth muscle cells. It plays a crucial role in regulating blood pressure via the modulation of peripheral vascular tone. Although several mechanisms have been suggested to explain PAR-2-induced hypotension, the precise mechanism remains to be elucidated. To investigate this possibility, we investigated the effects of PAR-2 activation on N-type Ca2+ currents (ICa-N) in isolated neurons of the celiac ganglion (CG), which is involved in the sympathetic regulation of mesenteric artery vascular tone. PAR-2 agonists irreversibly diminished voltage-gated Ca2+ currents (ICa), measured using the patch-clamp method, in rat CG neurons, whereas thrombin had little effect on ICa. This PAR-2-induced inhibition was almost completely prevented by ω-CgTx, a potent N-type Ca2+ channel blocker, suggesting the involvement of N-type Ca2+ channels in PAR-2-induced inhibition. In addition, PAR-2 agonists inhibited ICa–N in a voltage-independent manner in rat CG neurons. Moreover, PAR-2 agonists reduced action potential (AP) firing frequency as measured using the current-clamp method in rat CG neurons. This inhibition of AP firing induced by PAR-2 agonists was almost completely prevented by ω-CgTx, indicating that PAR-2 activation may regulate the membrane excitability of peripheral sympathetic neurons through modulation of N-type Ca2+ channels. In conclusion, the present findings demonstrate that the activation of PAR-2 suppresses peripheral sympathetic outflow by modulating N-type Ca2+ channel activity, which appears to be involved in PAR-2-induced hypotension, in peripheral sympathetic nerve terminals. PMID:25410909

PAR1 activation affects the neurotrophic properties of Schwann cells.

PubMed

Pompili, Elena; Fabrizi, Cinzia; Somma, Francesca; Correani, Virginia; Maras, Bruno; Schininà, Maria Eugenia; Ciraci, Viviana; Artico, Marco; Fornai, Francesco; Fumagalli, Lorenzo

2017-03-01

Protease-activated receptor-1 (PAR1) is the prototypic member of a family of four G-protein-coupled receptors that signal in response to extracellular proteases. In the peripheral nervous system, the expression and/or the role of PARs are still poorly investigated. High PAR1 mRNA expression was found in the rat dorsal root ganglia and the signal intensity of PAR1 mRNA increased in response to sciatic nerve transection. In the sciatic nerve, functional PAR1 receptor was reported at the level of non-compacted Schwann cell myelin microvilli of the nodes of Ranvier. Schwann cells are the principal population of glial cells of the peripheral nervous system which myelinate axons playing an important role during axonal regeneration and remyelination. The present study was undertaken in order to determine if the activation of PAR1 affects the neurotrophic properties of Schwann cells. Our results suggest that the stimulation of PAR1 could potentiate the Schwann cell ability to favour nerve regeneration. In fact, the conditioned medium obtained from Schwann cell cultures challenged with a specific PAR1 activating peptide (PAR1 AP) displays increased neuroprotective and neurotrophic properties with respect to the culture medium from untreated Schwann cells. The proteomic analysis of secreted proteins in untreated and PAR1 AP-treated Schwann cells allowed the identification of factors differentially expressed in the two samples. Some of them (such as macrophage migration inhibitory factor, matrix metalloproteinase-2, decorin, syndecan 4, complement C1r subcomponent, angiogenic factor with G patch and FHA domains 1) appear to be transcriptionally regulated after PAR1 AP treatment as shown by RT-PCR. Copyright © 2017 Elsevier Inc. All rights reserved.

Paternal age related schizophrenia (PARS): Latent subgroups detected by k-means clustering analysis.

PubMed

Lee, Hyejoo; Malaspina, Dolores; Ahn, Hongshik; Perrin, Mary; Opler, Mark G; Kleinhaus, Karine; Harlap, Susan; Goetz, Raymond; Antonius, Daniel

2011-05-01

Paternal age related schizophrenia (PARS) has been proposed as a subgroup of schizophrenia with distinct etiology, pathophysiology and symptoms. This study uses a k-means clustering analysis approach to generate hypotheses about differences between PARS and other cases of schizophrenia. We studied PARS (operationally defined as not having any family history of schizophrenia among first and second-degree relatives and fathers' age at birth ≥ 35 years) in a series of schizophrenia cases recruited from a research unit. Data were available on demographic variables, symptoms (Positive and Negative Syndrome Scale; PANSS), cognitive tests (Wechsler Adult Intelligence Scale-Revised; WAIS-R) and olfaction (University of Pennsylvania Smell Identification Test; UPSIT). We conducted a series of k-means clustering analyses to identify clusters of cases containing high concentrations of PARS. Two analyses generated clusters with high concentrations of PARS cases. The first analysis (N=136; PARS=34) revealed a cluster containing 83% PARS cases, in which the patients showed a significant discrepancy between verbal and performance intelligence. The mean paternal and maternal ages were 41 and 33, respectively. The second analysis (N=123; PARS=30) revealed a cluster containing 71% PARS cases, of which 93% were females; the mean age of onset of psychosis, at 17.2, was significantly early. These results strengthen the evidence that PARS cases differ from other patients with schizophrenia. Hypothesis-generating findings suggest that features of PARS may include a discrepancy between verbal and performance intelligence, and in females, an early age of onset. These findings provide a rationale for separating these phenotypes from others in future clinical, genetic and pathophysiologic studies of schizophrenia and in considering responses to treatment. Copyright © 2011 Elsevier B.V. All rights reserved.

Pharmacophore-based virtual screening, biological evaluation and binding mode analysis of a novel protease-activated receptor 2 antagonist

NASA Astrophysics Data System (ADS)

Cho, Nam-Chul; Seo, Seoung-Hwan; Kim, Dohee; Shin, Ji-Sun; Ju, Jeongmin; Seong, Jihye; Seo, Seon Hee; Lee, Iiyoun; Lee, Kyung-Tae; Kim, Yun Kyung; No, Kyoung Tai; Pae, Ae Nim

2016-08-01

Protease-activated receptor 2 (PAR2) is a G protein-coupled receptor, mediating inflammation and pain signaling in neurons, thus it is considered to be a potential therapeutic target for inflammatory diseases. In this study, we performed a ligand-based virtual screening of 1.6 million compounds by employing a common-feature pharmacophore model and two-dimensional similarity search to identify a new PAR2 antagonist. The common-feature pharmacophore model was established based on the biological screening results of our in-house library. The initial virtual screening yielded a total number of 47 hits, and additional biological activity tests including PAR2 antagonism and anti-inflammatory effects resulted in a promising candidate, compound 43, which demonstrated an IC50 value of 8.22 µM against PAR2. In next step, a PAR2 homology model was constructed using the crystal structure of the PAR1 as a template to explore the binding mode of the identified ligands. A molecular docking method was optimized by comparing the binding modes of a known PAR2 agonist GB110 and antagonist GB83, and applied to predict the binding mode of our hit compound 43. In-depth docking analyses revealed that the hydrophobic interaction with Phe2435.39 is crucial for PAR2 ligands to exert antagonistic activity. MD simulation results supported the predicted docking poses that PAR2 antagonist blocked a conformational rearrangement of Na+ allosteric site in contrast to PAR2 agonist that showed Na+ relocation upon GPCR activation. In conclusion, we identified new a PAR2 antagonist together with its binding mode, which provides useful insights for the design and development of PAR2 ligands.

Activation of PAR-2 elicits NO-dependent and CGRP-independent dilation of the dural artery.

PubMed

Bhatt, Deepak K; Ploug, Kenneth B; Ramachandran, Roshni; Olesen, Jes; Gupta, Saurabh

2010-06-01

The goal of this study was to determine the vascular effects of protease-activated receptor-2 (PAR-2) activation in the rat cranial vasculature. The role of PAR-2 in pain and inflammatory conditions has been established but the information available on its effects and receptor distribution in the trigeminal vascular axis is limited. We studied the dilatory function and expression of PAR-2 in the neuro-vascular circuit, critical in migraine pathogenesis. We also investigated the interaction of PAR-2 with calcitonin gene-related peptide (CGRP) and dural mast cells. We used an improved model of intravital microscopy on the closed cranial window in rats to study the vascular effects of PAR-2 activating peptides (PAR-2 APs; SLIGRL-NH(2), 2-Furoyl-LIGRLO-NH(2)) in the dural vasculature. Measurement of immunoreactive CGRP in skull halves and in trigeminal nucleus caudalis was done by using an enzyme-linked immunosorbent assay. We also analyzed the presence of PAR-2 in different migraine relevant tissues by quantitative real-time PCR and Western blot analysis. PAR-2 APs and trypsin induced a dose-dependent increase in dural artery diameter. The topical application of a nonspecific nitric oxide synthase (NOS) inhibitor, L-N(G)-Nitroarginine methyl ester, attenuated SLIGRL-NH(2) responses. Olcegepant, a CGRP receptor antagonist, did not a have significant effect on the SLIGRL-NH(2) responses, though exogenous CGRP responses were completely blocked. There was no significant release of CGRP from skull halves incubated with SLIGRL-NH(2) as compared with those incubated with the corresponding negative peptide. Chronic mast cell degranulation did not change the vascular effects of PAR-2 APs. mRNA and protein expression of PAR-2 were found throughout trigeminovasuclar axis. PAR-2 activation leads to vasodilation of dural arteries and these responses are partially mediated by nitric oxide. As PAR-2 is present throughout trigeminovasuclar axis, it may have a role in migraine pathogenesis, independent of CGRP and mast cell mediated mechanism.

Proteinase-activated receptor 4 stimulation-induced epithelial-mesenchymal transition in alveolar epithelial cells

PubMed Central

Ando, Seijitsu; Otani, Hitomi; Yagi, Yasuhiro; Kawai, Kenzo; Araki, Hiromasa; Fukuhara, Shirou; Inagaki, Chiyoko

2007-01-01

Background Proteinase-activated receptors (PARs; PAR1–4) that can be activated by serine proteinases such as thrombin and neutrophil catepsin G are known to contribute to the pathogenesis of various pulmonary diseases including fibrosis. Among these PARs, especially PAR4, a newly identified subtype, is highly expressed in the lung. Here, we examined whether PAR4 stimulation plays a role in the formation of fibrotic response in the lung, through alveolar epithelial-mesenchymal transition (EMT) which contributes to the increase in myofibroblast population. Methods EMT was assessed by measuring the changes in each specific cell markers, E-cadherin for epithelial cell, α-smooth muscle actin (α-SMA) for myofibroblast, using primary cultured mouse alveolar epithelial cells and human lung carcinoma-derived alveolar epithelial cell line (A549 cells). Results Stimulation of PAR with thrombin (1 U/ml) or a synthetic PAR4 agonist peptide (AYPGKF-NH2, 100 μM) for 72 h induced morphological changes from cobblestone-like structure to elongated shape in primary cultured alveolar epithelial cells and A549 cells. In immunocytochemical analyses of these cells, such PAR4 stimulation decreased E-cadherin-like immunoreactivity and increased α-SMA-like immunoreactivity, as observed with a typical EMT-inducer, tumor growth factor-β (TGF-β). Western blot analyses of PAR4-stimulated A549 cells also showed similar changes in expression of these EMT-related marker proteins. Such PAR4-mediated changes were attenuated by inhibitors of epidermal growth factor receptor (EGFR) kinase and Src. PAR4-mediated morphological changes in primary cultured alveolar epithelial cells were reduced in the presence of these inhibitors. PAR4 stimulation increased tyrosine phosphorylated EGFR or tyrosine phosphorylated Src level in A549 cells, and the former response being inhibited by Src inhibitor. Conclusion PAR4 stimulation of alveolar epithelial cells induced epithelial-mesenchymal transition (EMT) as monitored by cell shapes, and epithelial or myofibroblast marker at least partly through EGFR transactivation via receptor-linked Src activation. PMID:17433115

Pharmacodynamics of levofloxacin against characterized ciprofloxacin-resistant Streptococcus pneumoniae.

PubMed

Lister, Philip D

2008-09-01

In a previous study, levofloxacin 750 mg eradicated 4 ciprofloxacin-resistant isolates of Streptococcus pneumoniae from an in vitro pharmacodynamic model (IVPM). However, quinolone resistance-determining region (QRDR) mutations were not detected among those isolates. This study further evaluates levofloxacin 500 mg and 750 mg against S pneumoniae strains with characterized QRDR mutations. Six isolates with levofloxacin minimum inhibitory concentrations (MICs) of 2 to 4 microg/mL were selected for this study. Strains 5401, 5409, and 5437 contained only parC mutations. Three additional strains contained 2 mutations each: strain 5429 (parC and parE ), strain 5442 (parC and gyrA), and strain 5445 (parC and gyrB). Logarithmic-phase cultures (approximately 1 x 10(7) CFU/mL) were inoculated into the peripheral compartment of the IVPM and exposed to peak free-drug concentrations achieved with levofloxacin 500 mg and 750 mg (PO) and ciprofloxacin 750 mg (PO). Elimination pharmacokinetics were simulated and changes in viable counts were measured over 30 h. Ciprofloxacin exhibited very little antibacterial activity against the 6 strains, while levofloxacin 750 mg rapidly killed and eradicated the 3 parC mutant strains and the dual parC/parE mutant strains. Although levofloxacin 500 mg initially decreased viable counts by 4.5 to 6 logs, inoculum regrowth was observed between 12 and 24 h for the 6 strains. Regrowth was not due to the selection of mutant subpopulations. The pharmacodynamics of both levofloxacin doses were substantially diminished against the 2 strains with dual mutations in both parC and gyrA/B. The rapid eradication of single parC and dual parC/parE mutants with levofloxacin 750 mg demonstrates that this dose may slow the emergence of resistance due to these mutations. The decreased efficacy of both levofloxacin doses against the double parC and gyrA/B mutants highlights the importance of preventing the development and spread of double mutants.

Effect of PAR-2 Deficiency in Mice on KC Expression after Intratracheal LPS Administration

PubMed Central

Williams, Julie C.; Lee, Rebecca D.; Doerschuk, Claire M.; Mackman, Nigel

2011-01-01

Protease activated receptors (PAR) have been shown to play a role in inflammation. PAR-2 is expressed by numerous cells in the lung and has either proinflammatory, anti-inflammatory, or no effect depending on the model. Here, we examined the role of PAR-2 in a model of LPS-induced lung inflammation. We found that PAR-2-deficient mice had significantly less KC expression in bronchial lavage fluid compared with wild-type mice but there was no difference in MIP-2 or TNF-α expression. We also found that isolated alveolar and resident peritoneal macrophages lacking PAR-2 showed a similar deficit in KC after LPS stimulation without differences in MIP-2 or TNF-α. Infiltration of neutrophils and macrophages into the lung following LPS administration was not affected by an absence of PAR-2. Our results support the notion that PAR-2 plays a role in LPS activation of TLR4 signaling in macrophages. PMID:22175012

Effect of PAR-2 Deficiency in Mice on KC Expression after Intratracheal LPS Administration.

PubMed

Williams, Julie C; Lee, Rebecca D; Doerschuk, Claire M; Mackman, Nigel

2011-01-01

Protease activated receptors (PAR) have been shown to play a role in inflammation. PAR-2 is expressed by numerous cells in the lung and has either proinflammatory, anti-inflammatory, or no effect depending on the model. Here, we examined the role of PAR-2 in a model of LPS-induced lung inflammation. We found that PAR-2-deficient mice had significantly less KC expression in bronchial lavage fluid compared with wild-type mice but there was no difference in MIP-2 or TNF-α expression. We also found that isolated alveolar and resident peritoneal macrophages lacking PAR-2 showed a similar deficit in KC after LPS stimulation without differences in MIP-2 or TNF-α. Infiltration of neutrophils and macrophages into the lung following LPS administration was not affected by an absence of PAR-2. Our results support the notion that PAR-2 plays a role in LPS activation of TLR4 signaling in macrophages.

PAR(2) and temporomandibular joint inflammation in the rat.

PubMed

Denadai-Souza, A; Cenac, N; Casatti, C A; Câmara, P R de Souza; Yshii, L M; Costa, S K P; Vergnolle, N; Muscará, M N

2010-10-01

The proteinase-activated receptor 2 (PAR(2)) is a putative therapeutic target for arthritis. We hypothesized that the early pro-inflammatory effects secondary to its activation in the temporomandibular joint (TMJ) are mediated by neurogenic mechanisms. Immunofluorescence analysis revealed a high degree of neurons expressing PAR(2) in retrogradely labeled trigeminal ganglion neurons. Furthermore, PAR(2) immunoreactivity was observed in the lining layer of the TMJ, co-localizing with the neuronal marker PGP9.5 and substance-P-containing peripheral sensory nerve fibers. The intra-articular injection of PAR(2) agonists into the TMJ triggered a dose-dependent increase in plasma extravasation, neutrophil influx, and induction of mechanical allodynia. The pharmacological blockade of natural killer 1 (NK(1)) receptors abolished PAR(2)-induced plasma extravasation and inhibited neutrophil influx and mechanical allodynia. We conclude that PAR(2) activation is pro-inflammatory in the TMJ, through a neurogenic mechanism involving NK(1) receptors. This suggests that PAR(2) is an important component of innate neuro-immune response in the rat TMJ.

Tiam1 interaction with the PAR complex promotes talin-mediated Rac1 activation during polarized cell migration

PubMed Central

Wang, Shujie; Watanabe, Takashi; Matsuzawa, Kenji; Katsumi, Akira; Kakeno, Mai; Matsui, Toshinori; Ye, Feng; Sato, Kazuhide; Murase, Kiyoko; Sugiyama, Ikuko; Kimura, Kazushi; Mizoguchi, Akira; Ginsberg, Mark H.; Collard, John G.

2012-01-01

Migrating cells acquire front-rear polarity with a leading edge and a trailing tail for directional movement. The Rac exchange factor Tiam1 participates in polarized cell migration with the PAR complex of PAR3, PAR6, and atypical protein kinase C. However, it remains largely unknown how Tiam1 is regulated and contributes to the establishment of polarity in migrating cells. We show here that Tiam1 interacts directly with talin, which binds and activates integrins to mediate their signaling. Tiam1 accumulated at adhesions in a manner dependent on talin and the PAR complex. The interactions of talin with Tiam1 and the PAR complex were required for adhesion-induced Rac1 activation, cell spreading, and migration toward integrin substrates. Furthermore, Tiam1 acted with talin to regulate adhesion turnover. Thus, we propose that Tiam1, with the PAR complex, binds to integrins through talin and, together with the PAR complex, thereby regulates Rac1 activity and adhesion turnover for polarized migration. PMID:23071154

Characterization of a point mutation in the parC gene of Mycoplasma bovirhinis associated with fluoroquinolone resistance.

PubMed

Hirose, K; Kawasaki, Y; Kotani, K; Abiko, K; Sato, H

2004-05-01

Quinolone-resistant (QR) mutants of Mycoplasma bovirhinis strain PG43 (type strain) were generated by stepwise selection in increasing concentrations of enrofloxacin (ENR). An alteration was found in the quinolone resistance-determining region (QRDR) of the parC gene coding for the ParC subunit of topoisomerase IV from these mutants, but not in the gyrA, gyrB, and parE gene coding for the GyrA and GyrB subunits of DNA gyrase and the ParE subunit of topoisomerase IV. Similarly, such an alteration in QRDR of parC was found in the field isolates of M. bovirhinis, which possessed various levels of QR. The substitution of leucine (Leu) by serine (Ser) at position 80 of QRDR of ParC was observed in both QR-mutants and QR-isolates. This is the first report of QR based on a point mutation of the parC gene in M. bovirhinis.

Police accident report forms: safety device coding and enacted laws.

PubMed

Brock, K; Lapidus, G

2008-12-01

Safety device coding on state police accident report (PAR) forms was compared with provisions in state traffic safety laws. PAR forms were obtained from all 50 states and the District of Columbia (states/DC). For seat belts, 22 states/DC had a primary seat belt enforcement law vs 50 with a PAR code. For car seats, all 51 states/DC had a law and a PAR code. For booster seats, 39 states/DC had a law vs nine with a PAR code. For motorcycle helmets, 21 states/DC had an all-age rider helmet law and another 26 a partial-age law vs 50 with a PAR code. For bicycle helmets, 21 states/DC had a partial-age rider helmet law vs 48 with a PAR code. Therefore gaps in the ability of states to fully record accident data reflective of existing state traffic safety laws are revealed. Revising the PAR forms in all states to include complete variables for safety devices should be an important priority, independent of the laws.

Design of an Integrated-System FARAD Thruster

NASA Technical Reports Server (NTRS)

Polzin, K.A.; Rose, R.F.; Miller, R.; Owens, T.

2007-01-01

Pulsed inductive plasma accelerators are spacecraft propulsion devices in which energy is stored in a capacitor and then discharged through an inductive coil. The device is electrodeless, inducing a current s heet in a plasma located near the face of the coil. The propellant is accelerated and expelled at a high exhaust velocity (order of 10 km/s) through the interaction of the plasma current and the induced magne tic field, The Faraday Accelerator with RF-Assisted Discharge (FARAD) thruster is a type of pulsed inductive plasma accelerator in which t he plasma is preionized by a mechanism separate from that used to for m the current sheet and accelerate the gas. Employing a separate preionization mechanism allows for the formation of an inductive current s heet at much lower discharge energies and voltages than those used in previous pulsed inductive accelerators like the Pulsed Inductive Thr uster (PIT). In this paper, we present the design of a benchtop FARAD thruster with all the subsystems (mass injection, preionization, and acceleration) integrated into a single unit. Design of the thruster follows the guidelines and similarity performance parameters presented elsewhere. The system is designed to use the ringing, RF-frequency s ignal produced by a discharging Vector Inversion Generator (VIG) to p reionize the gas. The acceleration stage operates on the order of 100 J/pulse and can be driven by several different pulsed powertrains. These include a simple capacitor coupled to the system, a Bernardes and Merryman configuration, and a pulsecompression circuit that takes a temporally broad, low current pulse and transforms it into a short, h igh current pulse. A set of applied magnetic field coils are integrated into the system to guide the preionized propellant as it spreads ov er the face of the inductive acceleration coil. The coils are operate d in a pulsed mode, and the thruster can be operated without using the coils to determine if there is a performance improvement gain realiz ed when an applied field is present.

Precision of noninvasive hemoglobin-level measurement by pulse co-oximetry in patients admitted to intensive care units for severe gastrointestinal bleeds.

PubMed

Coquin, Julien; Dewitte, Antoine; Manach, Yannick Le; Caujolle, Marie; Joannes-Boyau, Olivier; Fleureau, Catherine; Janvier, Gérard; Ouattara, Alexandre

2012-09-01

Measurement of total hemoglobin, based on pulse co-oximetry, is a continuous and noninvasive method that has been principally evaluated in healthy volunteers subjected to hemodilution. We tested the hypothesis that its accuracy could adversely affect patients presenting with severe hemorrhage, which is traditionally associated with increased microvascular tone. Observational study. Twelve-bed mixed medico-surgical intensive care unit. Thirty-three patients admitted to our critical care unit for gastrointestinal bleeds were included. A spectrophotometric sensor was positioned on the patient's fingertip and connected to a pulse co-oximeter. During the first 24 hrs following admission, venous hemoglobin level was determined at the laboratory every 8 hrs and was compared with hemoglobin levels displayed on the pulse co-oximeter measurements screen and/or measured from capillary blood using a portable photometer. The primary end point was the percentage of inaccurate measurements, which were defined as >15% difference compared with reference values or their unavailability for any technical reason. Twenty-five (19%) measurements of pulse co-oximeter measurements were unavailable from the screen. Pulse co-oximeter measurements and capillary hemoglobin levels were significantly correlated to venous hemoglobin level. For venous hemoglobin level compared with pulse co-oximeter measurements (n = 105), and for venous hemoglobin level compared with capillary hemoglobin levels (n = 111), the biases were, respectively, 1.0 ± 1.9 g dL and 0.4 ± 1.0 g dL (p < .05). The proportion of inaccurate measurements was significantly higher for pulse co-oximeter measurements (56% vs. 15%, p < .05). Although the use of norepinephrine did not affect concordance parameters, unavailability of measurements was frequently observed (42% vs. 15%, p < .05). Determination of pulse co-oximetry-based hemoglobin in patients presenting with severe gastrointestinal bleeds can be inaccurate, which renders its use to guide transfusion decisions potentially hazardous. The unavailability of measurements, especially during vasopressor infusion, represents another serious limitation for hemorrhagic patients.

Relaxation diélectrique de solutions aqueuses d'éthylène glycol aux micro-ondes

NASA Astrophysics Data System (ADS)

Vicq, G.; Delbos, G.; Forniés Marquina, J. M.; Lamkaouchi, K.

1999-09-01

The study of dielectric properties of aqueous solutions of ethylene glycol in the frequency range 10 MHz - 20 GHz is reported as a function of water concentration at 20 circC. Some complex permittivity measurements were carried out using a precise reflectrometric method at 1.20, 3.26 and 9.45 GHz and some others using HP 8510 B network analyser from 45 MHz to 20 GHz and measurements by time domain reflectometry (T.D.R.). The dielectric relaxation analysis shows two domains of “Debye" dispersion for pure ethylene glycol and his aqueous solutions. Using a spectral decomposition, the static and high frequency dielectric constant and the relaxation time have been determined. The dielectric behaviour is interpreted by using the concept of Schallamach, concerning the mixtures of associated-associated liquids. Les auteurs présentent des séries de résultats de mesures en hyperfréquences concernant les permittivités diélectriques de l'éthylène-glycol et de ses solutions aqueuses à 20 circC, pour diverses concentrations, entre 100 MHz et 20 GHz. Ils ont utilisé trois techniques différentes : des mesures précises à trois fréquences fixes parfaitement stabilisées en guides d'ondes 1,20 ; 3,26 et 9,45 GHz par une méthode réflectométrique ; des mesures utilisant l'analyseur de réseau vectoriel HP 8510 B fonctionnant entre 45 MHz et 20 GHz ; et des mesures par réflectométrie en domaine de temps (R.D.T.). Ils montrent que l'analyse de la relaxation peut être représentée par la superposition de deux domaines de dispersion de type “Debye" pour l'éthylène glycol et ses solutions aqueuses. Par décomposition spectrales, ils déduisent la permittivité statique, les temps de relaxation et la permittivité à fréquence infinie à 20 circC? Ils proposent que ces mélanges soient de type associé-associé suivant le concept de Schallamach, qui montre que pour des mélanges de ce type, il existe des relaxations d'agrégats contenant les deux types de molécules plutôt que des relaxations de molécules individuelles.

Comparison of the lowest-order transverse-electric (TE1) and transverse-magnetic (TEM) modes of the parallel-plate waveguide for terahertz pulse applications.

PubMed

Mendis, Rajind; Mittleman, Daniel M

2009-08-17

We present a comprehensive experimental study comparing the propagation characteristics of the virtually unknown TE(1) mode to the well-known TEM mode of the parallel-plate waveguide (PPWG), for THz pulse applications. We demonstrate that it is possible to overcome the undesirable effects caused by the TE(1) mode's inherent low-frequency cutoff, making it a viable THz wave-guiding option, and that for certain applications, the TE(1) mode may even be more desirable than the TEM mode. This study presents a whole new dimension to the THz technological capabilities offered by the PPWG, via the possible use of the TE(1) mode. (c) 2009 Optical Society of America

Numerical and Experimental Characterization of a Composite Secondary Bonded Adhesive Lap Joint Using the Ultrasonics method

NASA Astrophysics Data System (ADS)

Kumar, M. R.; Ghosh, A.; Karuppannan, D.

2018-05-01

The construction of aircraft using advanced composites have become very popular during the past two decades, in which many innovative manufacturing processes, such as cocuring, cobonding, and secondary bonding processes, have been adopted. The secondary bonding process has become less popular than the other two ones because of nonavailability of process database and certification issues. In this article, an attempt is made to classify the quality of bonding using nondestructive ultrasonic inspection methods. Specimens were prepared and tested using the nondestructive ultrasonic Through Transmission (TT), Pulse Echo (PE), and air coupled guided wave techniques. It is concluded that the ultrasonic pulse echo technique is the best one for inspecting composite secondary bonded adhesive joints.

Laser direct writing of thin-film copper structures as a modification of lithographic processes

NASA Astrophysics Data System (ADS)

Meyer, F.; Ostendorf, A.; Stute, U.

2007-04-01

This paper presents a flexible, mask-free and efficient technique for UV-laser micropatterning of photosensitive resist by laser direct writing (LDW). Photo resist spun on gold sputtered silicon wafers has been laser structured by a scanner guided 266nm DPSSL and electroplated. Ablation behaviour and optimum seed layer preparation in relation to parameters like pulse energy, scanning speed and number of scanned cycles and the electroplating results are discussed. The resulting adhesive strength was measured by a µ-sear device and the gold seed layer-plated copper interface investigated by SEM and EDX to explain correlation to identified bonding behaviour. Improved adhesive strength was observed with higher laser pulse energy and reduced number of cycle.

Differential roles of kallikrein-related peptidase 6 in malignant transformation and ΔNp63β-mediated epithelial-mesenchymal transition of oral squamous cell carcinoma.

PubMed

Kaneko, Naoki; Kawano, Shintaro; Yasuda, Kaori; Hashiguchi, Yuma; Sakamoto, Taiki; Matsubara, Ryota; Goto, Yuichi; Jinno, Teppei; Maruse, Yasuyuki; Morioka, Masahiko; Hattori, Taichi; Tanaka, Shoichi; Tanaka, Hideaki; Kiyoshima, Tamotsu; Nakamura, Seiji

2017-12-01

We previously reported that epithelial-to-mesenchymal transition (EMT) was mediated by ΔNp63β in oral squamous cell carcinoma (OSCC). In this study, DNA microarray analyses were performed using ΔNp63β-overexpressing OSCC cells to identify genes associated with ΔNp63β-mediated EMT. Thereby, we focused on kallikrein-related peptidase (KLK) 6, most up-regulated following ΔNp63β-overexpression, that activates protease-activated receptors (PARs). In RT-PCR analyses, ΔNp63 was positively associated with KLK6 and PAR2 and negatively with PAR1 in OSCC cells. By ΔNp63 knockdown, KLK6 and PAR2 expression was decreased and PAR1 was increased. Furthermore, KLK6 knockdown led to enhancing migration and invasion, and inhibiting proliferation, suggesting EMT-phenotypes. Although, in the KLK6 or PAR2 knockdown cells, phosphorylation of ERK was reduced, it was restored in the KLK6 knockdown OSCC cells treated with recombinant KLK6 proteins. Immunohistochemistry showed ΔNp63, KLK6, and PAR2 were more strongly expressed in the epithelial dysplasia and central region of OSCC than normal oral epithelium, whereas PAR1 expression was undetectable. Interestingly, at the invasive front of OSCC, ΔNp63, KLK6, and PAR2 were reduced, but PAR1 was elevated. In addition, the OSCC patients with decreasing KLK6 expression at the invasive front had more unfavourable prognosis. These results suggested differential roles of KLK6 in malignant transformation and EMT; high ΔNp63β expression up-regulates KLK6-PAR2 and down-regulates PAR1, inducing malignant transformation in oral epithelium with stimulating proliferation through ERK signal activation. Moreover, KLK6-PAR2 expression is down-regulated and PAR1 is up-regulated when ΔNp63β expression is decreased, leading to EMT with enhancing migration and invasion through ERK signal reduction at the invasive front. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Spatiotemporal characteristics of photosynthetically active radiation in understory of Korean pine and broadleaved mixed forest in Changbai Mountains].

PubMed

Yuan, Feng-Hui; Guan, De-Xin; Wu, Jia-Bing; Wang, An-Zhi; Shi, Ting-Ting; Zhang, Xiao-Jing

2008-02-01

Based on the data of three years successive automatic measurement with five horizontal quantum PAR sensors, this paper studied the spatiotemporal characteristics of photosynthetically active radiation (PAR) in the understory of Korean pine and broadleaved mixed forest in Changbai Mountains, in contrast with above-canopy PAR. It was found that the annual dynamics of above-canopy PAR showed two or more peaks, which was mainly affected by the weather conditions such as cloudy, foggy and rainy events. The annual dynamics of understory PAR followed the same trend of above-canopy PAR in non-growth season, but was steady and lower in numerical value in growth season. On clear days, larger differences were observed in the diurnal variation and frequency distribution of the understory PAR. As for the spatial variation of the understory PAR, the coefficient of variation (CV) was smaller in non-growth season (about 0.15) than in growth season (> 0.22), with the greatest in August. On the clear days in growth season, the understory PAR had a greater spatial variation when the solar elevation angle was between 38 degrees and 48 degrees (at 9:00-10:00 or 13:00-14:00).

Full-length soluble urokinase plasminogen activator receptor down-modulates nephrin expression in podocytes

PubMed Central

Alfano, Massimo; Cinque, Paola; Giusti, Guido; Proietti, Silvia; Nebuloni, Manuela; Danese, Silvio; D’Alessio, Silvia; Genua, Marco; Portale, Federica; Lo Porto, Manuela; Singhal, Pravin C.; Rastaldi, Maria Pia; Saleem, Moin A.; Mavilio, Domenico; Mikulak, Joanna

2015-01-01

Increased plasma level of soluble urokinase-type plasminogen activator receptor (suPAR) was associated recently with focal segmental glomerulosclerosis (FSGS). In addition, different clinical studies observed increased concentration of suPAR in various glomerular diseases and in other human pathologies with nephrotic syndromes such as HIV and Hantavirus infection, diabetes and cardiovascular disorders. Here, we show that suPAR induces nephrin down-modulation in human podocytes. This phenomenon is mediated only by full-length suPAR, is time-and dose-dependent and is associated with the suppression of Wilms’ tumor 1 (WT-1) transcription factor expression. Moreover, an antagonist of αvβ3 integrin RGDfv blocked suPAR-induced suppression of nephrin. These in vitro data were confirmed in an in vivo uPAR knock out Plaur−/− mice model by demonstrating that the infusion of suPAR inhibits expression of nephrin and WT-1 in podocytes and induces proteinuria. This study unveiled that interaction of full-length suPAR with αvβ3 integrin expressed on podocytes results in down-modulation of nephrin that may affect kidney functionality in different human pathologies characterized by increased concentration of suPAR. PMID:26380915

Effects of tissue factor, PAR-2 and MMP-9 expression on human breast cancer cell line MCF-7 invasion.

PubMed

Lin, Zeng-Mao; Zhao, Jian-Xin; Duan, Xue-Ning; Zhang, Lan-Bo; Ye, Jing-Ming; Xu, Ling; Liu, Yin-Hua

2014-01-01

This study aimed to explore the expression of tissue factor (TF), protease activated receptor-2 (PAR-2), and matrix metalloproteinase-9 (MMP-9) in the MCF-7 breast cancer cell line and influence on invasiveness. Stable MCF-7 cells transfected with TF cDNA and with TF ShRNA were established. TF, PAR-2, and MMP-9 protein expression was analyzed using indirect immunofluorescence and invasiveness was evaluated using a cell invasion test. Effects of an exogenous PAR-2 agonist were also examined. TF protein expression significantly differed between the TF cDNA and TF ShRNA groups. MMP-9 protein expression was significantly correlated with TF protein expression, but PAR-2 protein expression was unaffected. The PAR- 2 agonist significantly enhanced MMP-9 expression and slightly increased TF and PAR-2 expression in the TF ShRNA group, but did not significantly affect protein expression in MCF-7 cells transfected with TF cDNA. TF and MMP-9 expression was positively correlated with the invasiveness of tumor cells. TF, PAR-2, and MMP-9 affect invasiveness of MCF-7 cells. TF may increase MMP-9 expression by activating PAR-2.

Role of thrombin signalling in platelets in haemostasis and thrombosis

NASA Astrophysics Data System (ADS)

Sambrano, Gilberto R.; Weiss, Ethan J.; Zheng, Yao-Wu; Huang, Wei; Coughlin, Shaun R.

2001-09-01

Platelets are critical in haemostasis and in arterial thrombosis, which causes heart attacks and other events triggered by abnormal clotting. The coagulation protease thrombin is a potent activator of platelets ex vivo. However, because thrombin also mediates fibrin deposition and because multiple agonists can trigger platelet activation, the relative importance of platelet activation by thrombin in haemostasis and thrombosis is unknown. Thrombin triggers cellular responses at least in part through protease-activated receptors (PARs). Mouse platelets express PAR3 and PAR4 (ref. 9). Here we show that platelets from PAR4-deficient mice failed to change shape, mobilize calcium, secrete ATP or aggregate in response to thrombin. This result demonstrates that PAR signalling is necessary for mouse platelet activation by thrombin and supports the model that mouse PAR3 (mPAR3) does not by itself mediate transmembrane signalling but instead acts as a cofactor for thrombin cleavage and activation of mPAR4 (ref. 10). Importantly, PAR4-deficient mice had markedly prolonged bleeding times and were protected in a model of arteriolar thrombosis. Thus platelet activation by thrombin is necessary for normal haemostasis and may be an important target in the treatment of thrombosis.

Offsets in fiber-coupled diode laser hygrometers caused by parasitic absorption effects and their prevention

NASA Astrophysics Data System (ADS)

Buchholz, B.; Ebert, V.

2014-07-01

Large systematic errors in absorption spectrometers (AS) can be caused by ‘parasitic’ optical absorption (parA) outside the measurement region. In particular, calibration-free direct tunable diode laser AS (dTDLAS) can take advantage of an effective parA-compensation to provide correct absolute values. However, parA also negatively affects calibrated AS in calibration frequency and stability. A common strategy to suppress parA in TDLAS systems is to fiber-couple the light source and even the detector. However, this can be a critical approach if the TDL spectrometer is validated/calibrated under laboratory conditions in ambient humidity and used afterwards in much drier and variable conditions, for example in aircrafts. This paper shows that, e.g., ‘hermetically sealed’ butterfly packages, despite fiber coupling, can possess fixed as well as variable parA sections. Two new methods for absolute parA-quantification in dTDLAS were developed, including a novel, fiber-coupled, parA-free I0-detector for permanent parA-monitoring. Their dependences on ambient humidity/pressure and temporal behavior were studied. For the example of a 1.4 µm dTDLAS hygrometer SEALDH-II with a commercial DFB-laser module and an extractive 1.5 m path cell, we quantified the parA-induced signal offsets and their dependence on cell pressure. The conversion of parA-uncertainty into H2O signal uncertainty was studied and an updated uncertainty budget including parA-uncertainty was derived. The studies showed that parA in commercial laser modules can cause substantial, systematic concentration offsets of ≈25 ppmv fixed and ≈100 ppmv variable offsets for one meter absorption path. Applying our parA-quantification techniques these offsets could be compensated by a factor of 20 to an overall offset uncertainty of 4.5 ppmv m-1. Finally, we developed an innovative, integrated, µ-pumped closed-loop air drying unit for the parA minimization and temporal stabilization in airborne laser hygrometers. This compact and light weight dryer eliminates the variable parA by ambient humidity in less than 120 min and is well suited for airborne applications as it fulfils all airborne operation and safety restrictions.

Neo-Positivist Intrusions, Post-Qualitative Challenges, and PAR's Generative Indeterminacies

ERIC Educational Resources Information Center

Miller, Janet L.

2017-01-01

Although committed to PAR's overarching aspirations, many advocates also have noted myriad complexities of engaging in PAR, where ambiguities and disarrays--all kinds of inconclusive evidence--can proliferate. Uncertainties especially can erupt if PAR education-focused projects are positioned, oxymoronically, as expected to produce "high…

Transient early neurotrophin release and delayed inflammatory cytokine release by microglia in response to PAR-2 stimulation

PubMed Central

2012-01-01

Activated microglia exerts both beneficial and deleterious effects on neurons, but the signaling mechanism controlling these distinct responses remain unclear. We demonstrated that treatment of microglial cultures with the PAR-2 agonist, 2-Furoyl-LIGRLO-NH2, evoked early transient release of BDNF, while sustained PAR-2 stimulation evoked the delayed release of inflammatory cytokines (IL-1β and TNF-α) and nitric oxide. Culture medium harvested during the early phase (at 1 h) of microglial activation induced by 2-Furoyl-LIGRLO-NH2 (microglial conditioned medium, MCM) had no deleterious effects on cultured neurons, while MCM harvested during the late phase (at 72 h) promoted DNA fragmentation and apoptosis as indicated by TUNEL and annexin/PI staining. Blockade of PAR-1 during the early phase of PAR-2 stimulation enhanced BDNF release (by 11%, small but significant) while a PAR-1 agonist added during the late phase (24 h after 2-Furoyl-LIGRLO-NH2 addition) suppressed the release of cytokines and NO. The neuroprotective and neurotoxic effects of activated microglial exhibit distinct temporal profiles that are regulated by PAR-1 and PAR-2 stimulation. It may be possible to facilitate neuronal recovery and repair by appropriately timed stimulation and inhibition of microglial PAR-1 and PAR-2 receptors. PMID:22731117

Tryptase - PAR2 axis in Experimental Autoimmune Prostatitis, a model for Chronic Pelvic Pain Syndrome

PubMed Central

Roman, Kenny; Done, Joseph D.; Schaeffer, Anthony J.; Murphy, Stephen F.; Thumbikat, Praveen

2014-01-01

Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) affects up to 15% of the male population and is characterized by pelvic pain. Mast cells are implicated in the murine experimental autoimmune prostatitis (EAP) model as key to chronic pelvic pain development. The mast cell mediator tryptase-β and its cognate receptor protease-activated receptor 2 (PAR2) are involved in mediating pain in other visceral disease models. Prostatic secretions and urines from CP/CPPS patients were examined for the presence of mast cell degranulation products. Tryptase-β and PAR2 expression were examined in murine experimental autoimmune prostatitis (EAP). Pelvic pain and inflammation were assessed in the presence or absence of PAR2 expression and upon PAR2 neutralization. Tryptase-β and carboxypeptidase A3 were elevated in CP/CPPS compared to healthy volunteers. Tryptase-β was capable of inducing pelvic pain and was increased in EAP along with its receptor PAR2. PAR2 was required for the development of chronic pelvic pain in EAP. PAR2 signaling in dorsal root ganglia lead to ERK1/2 phosphorylation and calcium influx. PAR2 neutralization using antibodies attenuated chronic pelvic pain in EAP. The tryptase-PAR2 axis is an important mediator of pelvic pain in EAP and may play a role in the pathogenesis of CP/CPPS. PMID:24726923

PAR-2, IL-4R, TGF-β and TNF-α in bronchoalveolar lavage distinguishes extrinsic allergic alveolitis from sarcoidosis.

PubMed

Matěj, Radoslav; Smětáková, Magdalena; Vašáková, Martina; Nováková, Jana; Sterclová, Martina; Kukal, Jaromír; Olejár, Tomáš

2014-08-01

Sarcoidosis (SARC) and extrinsic allergic alveolitis (EAA) share certain markers, making a differential diagnosis difficult even with histopathological investigation. In lung tissue, proteinase-activated receptor-2 (PAR-2) is primarily investigated with regard to epithelial and inflammatory perspectives. Varying levels of certain chemokines can be a useful tool for distinguishing EAA and SARC. Thus, in the present study, differences in the levels of transforming growth factor (TGF)-β1, tumor necrosis factor (TNF)-α, interleukin-4 receptor (IL-4R) and PAR-2 in bronchoalveolar lavage fluid (BALF) were compared, using an ELISA method, between 14 patients with EAA and six patients with SARC. Statistically significant higher levels of IL-4R, PAR-2 and the PAR-2/TGF-β1 and PAR-2/TNF-α ratios were observed in EAA patients as compared with SARC patients. Furthermore, the ratios of TNF-α/total protein, TGF-β1/PAR-2 and TNF-α/PAR-2 were significantly lower in EAA patients than in SARC patients. The results indicated a higher detection of PAR-2 in EAA samples in association with TNF-α and TGF-β levels. As EAA and PAR-2 in parallel belong to the Th2-mediated pathway, the results significantly indicated an association between this receptor and etiology. In addition, the results indicated that SARC is predominantly a granulomatous inflammatory disease, thus, higher levels of TNF-α are observed. Therefore, the detection of PAR-2 and investigated chemokines in BALF may serve as a useful tool in the differential diagnosis between EAA and SARC.

Hybrid fiber-rod laser

DOEpatents

Beach, Raymond J.; Dawson, Jay W.; Messerly, Michael J.; Barty, Christopher P. J.

2012-12-18

Single, or near single transverse mode waveguide definition is produced using a single homogeneous medium to transport both the pump excitation light and generated laser light. By properly configuring the pump deposition and resulting thermal power generation in the waveguide device, a thermal focusing power is established that supports perturbation-stable guided wave propagation of an appropriately configured single or near single transverse mode laser beam and/or laser pulse.

Fluorescence imaging in the upper gastrointestinal tract for the detection of dysplasic changes

NASA Astrophysics Data System (ADS)

Sukowski, Uwe; Ebert, Bernd; Ortner, Marianne; Mueller, Karsten; Voderholzer, W.; Weber-Eibel, J.; Dietel, M.; Lochs, Herbert; Rinneberg, Herbert H.

2001-10-01

During endoscopy of the esophagus fluorescence images were recorded at a delay of 20 ns after pulsed laser excitation simultaneously with conventional reflected white light images. To label malignant cells (dysplasia, tumor) 5-aminolaevulinic acid was applied prior to fluorescence guided bi-opsy. In this way pre-malignant and malignant lesions were detected not seen previously during routine endoscopy.

Stimulation of the substantia nigra influences the specification of memory-guided saccades

PubMed Central

Mahamed, Safraaz; Garrison, Tiffany J.; Shires, Joel

2013-01-01

In the absence of sensory information, we rely on past experience or memories to guide our actions. Because previous experimental and clinical reports implicate basal ganglia nuclei in the generation of movement in the absence of sensory stimuli, we ask here whether one output nucleus of the basal ganglia, the substantia nigra pars reticulata (nigra), influences the specification of an eye movement in the absence of sensory information to guide the movement. We manipulated the level of activity of neurons in the nigra by introducing electrical stimulation to the nigra at different time intervals while monkeys made saccades to different locations in two conditions: one in which the target location remained visible and a second in which the target location appeared only briefly, requiring information stored in memory to specify the movement. Electrical manipulation of the nigra occurring during the delay period of the task, when information about the target was maintained in memory, altered the direction and the occurrence of subsequent saccades. Stimulation during other intervals of the memory task or during the delay period of the visually guided saccade task had less effect on eye movements. On stimulated trials, and only when the visual stimulus was absent, monkeys occasionally (∼20% of the time) failed to make saccades. When monkeys made saccades in the absence of a visual stimulus, stimulation of the nigra resulted in a rotation of the endpoints ipsilaterally (∼2°) and increased the reaction time of contralaterally directed saccades. When the visual stimulus was present, stimulation of the nigra resulted in no significant rotation and decreased the reaction time of contralaterally directed saccades slightly. Based on these measurements, stimulation during the delay period of the memory-guided saccade task influenced the metrics of saccades much more than did stimulation during the same period of the visually guided saccade task. Because these effects occurred with manipulation of nigral activity well before the initiation of saccades and in trials in which the visual stimulus was absent, we conclude that information from the basal ganglia influences the specification of an action as it is evolving primarily during performance of memory-guided saccades. When visual information is available to guide the specification of the saccade, as occurs during visually guided saccades, basal ganglia information is less influential. PMID:24259551

Shifting Patterns of Pasturelands and Stocking Rates of Cattle in Brazil: 1940 to 2012

NASA Astrophysics Data System (ADS)

Dias, L. C. P.; Santos, A.; Pimenta, F. M.; Costa, M. H.

2015-12-01

In this work, we investigate the shifting in historical patterns of pastureland (natural and planted) in Brazil using a new high-resolution (approximately 1 km x 1 km) spatially explicit reconstruction of land use from 1940 to 2012 and stocking rate of cattle maps from 1990 to 2012. We also identified the top 5% (highest yields) pixels in the 2010 stocking rate map and we assessed the historical trends in intensification and extensification practices in Brazil. We focus our analyzes in Amazonia and Cerrado biomes, in Mato Grosso and Pará states, and in the new agricultural frontier called MATOPIBA - which is formed by Maranhão, Tocantins, Piauí, and Bahia states. Natural pastureland expanded until the 1970s and, after that, most areas with natural pasture were replaced by planted pasture, which is more profitable. In 2012, natural pastures were still predominant in the Pampas (located in southern Rio Grande do Sul) and the Pantanal (located in western Mato Grosso do Sul). On the other hand, planted pastureland expanded in area between 1975 and 2012, especially in the Cerrado biome. Brazilian stocking rate of cattle increased, but remains close to 1.0 head/ha between 1990 and 2010 and the top 5% were about twice as high as the average in all regions analyzed. The yield gap (difference between average and the top 5% pixels) was largest in Pará state, where the stocking rate of cattle was below 50% of the potential given 2010 practices. The increase in cattle production in Amazonia biome and in the states of Mato Grosso and Pará came from both intensification and expansion of pasturelands. In contrast, pasturelands in Cerrado and MATOPIBA decreased in area while stocking rates of cattle increased gradually. Our results provide new insights about land use change and productivity in Brazilian territory that could guide future agricultural and conservation discussions, decisions, and policies.

Nouvelle approche à la prise en charge des condylomes

PubMed Central

Lopaschuk, Catharine C.

2013-01-01

Résumé Objectif Faire le résumé des anciens et des nouveaux moyens de traitement des verrues génitales ou condylomes et déterminer comment les utiliser de manière appropriée. Sources des données Une recherche documentaire a été effectuée dans les bases de données suivantes: MEDLINE, PubMed, EMBASE, base de données des synthèses systématiques et registre central des études contrôlées de la Collaboration Cochrane (en anglais), ACP Journal Club et Trip. Les bibliographies des articles extraits ont aussi été examinées. Les études cliniques, les articles de révision qualitative, les rapports consensuels et les guides de pratique clinique ont été retenus. Message principal Les verrues symptomatiques sont présentes chez au moins 1 % des personnes âgées entre 15 et 49 ans et on estime que jusqu’à 50 % des gens sont infectés par le virus du papillome humain à un moment donné de leur vie. L’imiquimod et la podophyllotoxine sont 2 nouveaux traitements pour les verrues génitales externes qui sont moins douloureux et peuvent être appliqués par les patients à la maison. De plus, il a été démontré que le vaccin quadrivalent contre le virus du papillome humain est efficace pour prévenir les condylomes et le cancer du col. Les plus anciennes méthodes thérapeutiques ont aussi leur place dans certaines situations, comme les verrues intravaginales, urétrales, anales ou récalcitrantes ou encore pour les patientes enceintes. Conclusion Les nouveaux traitements des verrues génitales externes peuvent réduire la douleur causée par la thérapie et le nombre de visites au cabinet. Les autres méthodes thérapeutiques demeurent utiles dans certaines situations.

High Power Microwave Emission of Large and Small Orbit Gyrotron Devices in Rectangular Interaction Structures

NASA Astrophysics Data System (ADS)

Hochman, J. M.; Gilgenbach, R. M.; Jaynes, R. L.; Rintamaki, J. I.; Luginsland, J. W.; Lau, Y. Y.; Spencer, T. A.

1996-11-01

Experiments utilize large and small orbit e-beam gyrotron devices in a rectangular-cross-section (RCS) gyrotron. This device is being explored to examine polarization control. Other research issues include pulse shortening, and mode competition. MELBA generates electron beams with parameters of: -800kV, 1-10kA diode current, and 0.5-1.0 μ sec pulselengths. The small orbit gyrotron device is converted to a large orbit experiment by running MELBA's annular electron beam through a magnetic cusp. Initial experiments showed an increase in beam alpha (V_perp/V_par) of a factor of ~ 4 between small and large orbit devices. Experimental results from the RCS gyrotron will be compared for large-orbit and small-orbit electron beams. Beam transport data and frequency measurements will be presented. Computer modeling utilizing the MAGIC and E-gun codes will be shown.

An airport wind shear detection and warning system using Doppler radar: A feasibility study

NASA Technical Reports Server (NTRS)

Mccarthy, J.; Blick, E. F.; Elmore, K. L.

1981-01-01

A feasibility study was conducted to determine whether ground based Doppler radar could measure the wind along the path of an approaching aircraft with sufficient accuracy to predict aircraft performance. Forty-three PAR approaches were conducted, with 16 examined in detail. In each, Doppler derived longitudinal winds were compared to aircraft measured winds; in approximately 75 percent of the cases, the Doppler and aircraft winds were in acceptable agreement. In the remaining cases, errors may have been due to a lack of Doppler resolution, a lack of co-location of the two sampling volumes, the presence of eddy or vortex like disturbances within the pulse volume, or the presence of point targets in antenna side lobes. It was further concluded that shrouding techniques would have reduced the side lobe problem. A ground based Doppler radar operating in the optically clear air, provides the appropriate longitudinal winds along an aircraft's intended flight path.

Estimating Photosynthetically Available Radiation (PAR) at the Earth's surface from satellite observations

NASA Technical Reports Server (NTRS)

Frouin, Robert

1993-01-01

Current satellite algorithms to estimate photosynthetically available radiation (PAR) at the earth' s surface are reviewed. PAR is deduced either from an insolation estimate or obtained directly from top-of-atmosphere solar radiances. The characteristics of both approaches are contrasted and typical results are presented. The inaccuracies reported, about 10 percent and 6 percent on daily and monthly time scales, respectively, are useful to model oceanic and terrestrial primary productivity. At those time scales variability due to clouds in the ratio of PAR and insolation is reduced, making it possible to deduce PAR directly from insolation climatologies (satellite or other) that are currently available or being produced. Improvements, however, are needed in conditions of broken cloudiness and over ice/snow. If not addressed properly, calibration/validation issues may prevent quantitative use of the PAR estimates in studies of climatic change. The prospects are good for an accurate, long-term climatology of PAR over the globe.

The polarity protein partitioning-defective 1 (PAR-1) regulates dendritic spine morphogenesis through phosphorylating postsynaptic density protein 95 (PSD-95).

PubMed

Wu, Qian; DiBona, Victoria L; Bernard, Laura P; Zhang, Huaye

2012-08-31

The polarity protein PAR-1 plays an essential role in many cellular contexts, including embryogenesis, asymmetric cell division, directional migration, and epithelial morphogenesis. Despite its known importance in different cellular processes, the role of PAR-1 in neuronal morphogenesis is less well understood. In particular, its role in the morphogenesis of dendritic spines, which are sites of excitatory synaptic inputs, has been unclear. Here, we show that PAR-1 is required for normal spine morphogenesis in hippocampal neurons. We further show that PAR-1 functions through phosphorylating the synaptic scaffolding protein PSD-95 in this process. Phosphorylation at a conserved serine residue in the KXGS motif in PSD-95 regulates spine morphogenesis, and a phosphomimetic mutant of this site can rescue the defects of kinase-dead PAR-1. Together, our findings uncover a role of PAR-1 in spine morphogenesis in hippocampal neurons through phosphorylating PSD-95.

Amylose primitive médiastinale d'aspect pseudotumoral

PubMed Central

Mahfoudhi, Madiha; Mamlouk, Habiba; Turki, Sami; Kheder, Adel

2015-01-01

L'amylose primitive médiastinale isolée est rare et de diagnostic difficile. Nous rapportons l'observation d'un patient âgé de 41 ans ayant présenté une dyspnée et des crachats hémoptoïques. A l'examen physique il n'avait pas d'hypotension orthostatique. Les aires ganglionnaires périphériques étaient libres. La tomodensitométrie thoracique a objectivé un magma d'adénopathies médiastinales réalisant une masse de 45 mm x 60 mm. L'examen anatomopathologique d'une biopsie ganglionnaire guidée par médiastinoscopie a conclut a une amylose médiastinale de type AL. Il n'avait pas d'autres localisations amyloïdes. Un myélome multiple a été éliminé. Le diagnostic d'amylose primitive médiastinale de type AL a été retenu. Le traitement s'est basé sur des cures de Melphalan-prednisone. La chirurgie était évitée vu le risque hémorragique élevé. L’évolution était marquée par l'amélioration de la dyspnée, la disparition de l'hémoptysie et la diminution de la taille de la masse ganglionnaire devenant 25 mm x 20 mm. PMID:26308913

Cerebral Oxygen Saturation to Guide Oxygen Delivery in Preterm Neonates for the Immediate Transition after Birth: A 2-Center Randomized Controlled Pilot Feasibility Trial.

PubMed

Pichler, Gerhard; Urlesberger, Berndt; Baik, Nariae; Schwaberger, Bernhard; Binder-Heschl, Corinna; Avian, Alexander; Pansy, Jasmin; Cheung, Po-Yin; Schmölzer, Georg Marcus

2016-03-01

To assess if monitoring of cerebral regional tissue oxygen saturation (crSO2) using near-infrared spectroscopy (NIRS) to guide respiratory and supplemental oxygen support reduces burden of cerebral hypoxia and hyperoxia in preterm neonates during resuscitation after birth. Preterm neonates <34(+0) weeks of gestation were included in a prospective randomized controlled pilot feasibility study at 2 tertiary level neonatal intensive care units. In a NIRS-visible group, crSO2 monitoring in addition to pulse oximetry was used to guide respiratory and supplemental oxygen support during the first 15 minutes after birth. In a NIRS-not-visible group, only pulse oximetry was used. The primary outcomes were burden of cerebral hypoxia (<10th percentile) or hyperoxia (>90th percentile) measured in %minutes crSO2 during the first 15 minutes after birth. Secondary outcomes were all cause of mortality and/or cerebral injury and neurologic outcome at term age. Allocation sequence was 1:1 with block-randomization of 30 preterm neonates at each site. In the NIRS-visible group burden of cerebral hypoxia in %minutes, crSO2 was halved, and the relative reduction was 55.4% (95% CI 37.6-73.2%; P = .028). Cerebral hyperoxia was observed in NIRS-visible group in 3 neonates with supplemental oxygen and in NIRS-not-visible group in 2. Cerebral injury rate and neurologic outcome at term age was similar in both groups. Two neonates died in the NIRS-not-visible group and none in the NIRS-visible group. No severe adverse reactions were observed. Reduction of burden of cerebral hypoxia during immediate transition and resuscitation after birth is feasible by crSO2 monitoring to guide respiratory and supplemental oxygen support. ClinicalTrials.gov: NCT02017691. Copyright © 2016 Elsevier Inc. All rights reserved.

Is There an "F" in Your PAR? Understanding, Teaching and Doing Action Research

ERIC Educational Resources Information Center

Lorenzetti, Liza; Walsh, Christine Ann

2014-01-01

Participatory Action Research (PAR) is increasingly recognized within academic research and pedagogy. What are the benefits of including feminism within participatory action research and teaching? In responding to this question, we discuss the similarities and salient differences between PAR and feminist informed PAR (FPAR). There are eight themes…

PAR-2 receptor-induced effects on human eccrine sweat gland cells.

PubMed

L Bovell, Douglas; Kofler, Barbara; Lang, Roland

2009-01-01

Serine proteases can induce cell signaling by stimulating G-protein-coupled receptors, called proteinase-activated receptors (PAR's) on a variety of epithelial cells. While PAR-2, one such receptor, activates cell signaling in a secretory cell line derived from human sweat glands, there was no information on their presence and effects on intact sweat glands. PAR-2 presence and activation of eccrine sweat glands isolated from human skin samples was investigated using Western blot analysis, immunohistochemistry, electron microscopy (EM) and Ca(2+) imaging. Anti-human PAR-2 antibody demonstrated the presence of these receptors in eccrine sweat glands. EM showed that PAR-2 activation resulted in degranulation of secretory cells. Ca(2+) imaging using PAR-2 activators demonstrated a two phase increase in [Ca(2+)](i) which was dependent on extracellular Ca(2+) for the second phase, and that the response could be blocked by prior incubation with xestospongin, the IP(3) receptor blocker. The results demonstrated that PAR-2 receptors are present in human sweat gland secretory cells and that these receptors are functionally active and can induce changes associated with secretory events in eccrine glands.

Protease Activated Receptor-2 Contributes to Heart Failure

PubMed Central

Antoniak, Silvio; Sparkenbaugh, Erica M.; Tencati, Michael; Rojas, Mauricio; Mackman, Nigel; Pawlinski, Rafal

2013-01-01

Heart failure is a major clinical problem worldwide. Previous studies have demonstrated an important role for G protein-coupled receptors, including protease-activated receptors (PARs), in the pathology of heart hypertrophy and failure. Activation of PAR-2 on cardiomyocytes has been shown to induce hypertrophic growth in vitro. PAR-2 also contributes to myocardial infarction and heart remodeling after ischemia/reperfusion injury. In this study, we found that PAR-2 induced hypertrophic growth of cultured rat neonatal cardiomyocytes in a MEK1/2 and p38 dependent manner. In addition, PAR-2 activation on mouse cardiomyocytes increased expression of the pro-fibrotic chemokine MCP-1. Furthermore, cardiomyocyte-specific overexpression of PAR-2 in mice induced heart hypertrophy, cardiac fibrosis, inflammation and heart failure. Finally, in a mouse model of myocardial infarction induced by permanent ligation of the left anterior descending coronary artery, PAR-2 deficiency attenuated heart remodeling and improved heart function independently of its contribution to the size of the initial infarct. Taken together, our data indicate that PAR-2 signaling contributes to the pathogenesis of hypertrophy and heart failure. PMID:24312345

The protease-activated receptor-2 upregulates keratinocyte phagocytosis.

PubMed

Sharlow, E R; Paine, C S; Babiarz, L; Eisinger, M; Shapiro, S; Seiberg, M

2000-09-01

The protease-activated receptor-2 (PAR-2) belongs to the family of seven transmembrane domain receptors, which are activated by the specific enzymatic cleavage of their extracellular amino termini. Synthetic peptides corresponding to the tethered ligand domain (SLIGRL in mouse, SLIGKV in human) can activate PAR-2 without the need for receptor cleavage. PAR-2 activation is involved in cell growth, differentiation and inflammatory processes, and was shown to affect melanin and melanosome ingestion by human keratinocytes. Data presented here suggest that PAR-2 activation may regulate human keratinocyte phagocytosis. PAR-2 activation by trypsin, SLIGRL or SLIGKV increased the ability of keratinocytes to ingest fluorescently labeled microspheres or E. coli K-12 bioparticles. This PAR-2 mediated increase in keratinocyte phagocytic capability correlated with an increase in actin polymerization and *-actinin reorganization, cell surface morphological changes and increased soluble protease activity. Moreover, addition of serine protease inhibitors downmodulated both the constitutive and the PAR-2 mediated increases in phagocytosis, suggesting that serine proteases mediate this functional activity in keratinocytes. PAR-2 involvement in keratinocyte phagocytosis is a novel function for this receptor.

Matrix metalloproteases and PAR1 activation

PubMed Central

Austin, Karyn M.; Covic, Lidija

2013-01-01

Cardiovascular diseases, including atherothrombosis, are the leading cause of morbidity and mortality in the United States, Europe, and the developed world. Matrix metalloproteases (MMPs) have recently emerged as important mediators of platelet and endothelial function, and atherothrombotic disease. Protease-activated receptor-1 (PAR1) is a G protein-coupled receptor that is classically activated through cleavage of the N-terminal exodomain by the serine protease thrombin. Most recently, 2 MMPs have been discovered to have agonist activity for PAR1. Unexpectedly, MMP-1 and MMP-13 cleave the N-terminal exodomain of PAR1 at noncanonical sites, which result in distinct tethered ligands that activate G-protein signaling pathways. PAR1 exhibits metalloprotease-specific signaling patterns, known as biased agonism, that produce distinct functional outputs by the cell. Here we contrast the mechanisms of canonical (thrombin) and noncanonical (MMP) PAR1 activation, the contribution of MMP-PAR1 signaling to diseases of the vasculature, and the therapeutic potential of inhibiting MMP-PAR1 signaling with MMP inhibitors, including atherothrombotic disease, in-stent restenosis, heart failure, and sepsis. PMID:23086754

Protease-Activated Receptor-2 Deficiency Attenuates Atherosclerotic Lesion Progression and Instability in Apolipoprotein E-Deficient Mice

PubMed Central

Zuo, Pengfei; Zuo, Zhi; Zheng, Yueyue; Wang, Xin; Zhou, Qianxing; Chen, Long; Ma, Genshan

2017-01-01

Inflammatory mechanisms are involved in the process of atherosclerotic plaque formation and rupture. Accumulating evidence suggests that protease-activated receptor (PAR)-2 contributes to the pathophysiology of chronic inflammation on the vasculature. To directly examine the role of PAR-2 in atherosclerosis, we generated apolipoprotein E/PAR-2 double-deficient mice. Mice were fed with high-fat diet for 12 weeks starting at ages of 6 weeks. PAR-2 deficiency attenuated atherosclerotic lesion progression with reduced total lesion area, reduced percentage of stenosis and reduced total necrotic core area. PAR-2 deficiency increased fibrous cap thickness and collagen content of plaque. Moreover, PAR-2 deficiency decreased smooth muscle cell content, macrophage accumulation, matrix metallopeptidase-9 expression and neovascularization in plaque. Relative quantitative PCR assay using thoracic aorta revealed that PAR-2 deficiency reduced mRNA expression of inflammatory molecules, such as vascular cell adhesion molecule-1, intercellular adhesion molecule-1, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1. In vitro experiment, we found that PAR-2 deficiency reduced mRNA expression of interferon-γ, interleukin-6, TNF-α and MCP-1 in macrophage under unstimulated and lipopolysaccharide-stimulated conditions. These results suggest that PAR-2 deficiency attenuates the progression and instability of atherosclerotic plaque. PMID:28959204

The expression and activation of protease-activated receptor-2 correlate with skin color.

PubMed

Babiarz-Magee, Laura; Chen, Nannan; Seiberg, Miri; Lin, Connie B

2004-06-01

Skin color results from the production and distribution of melanin in the epidermis. The protease-activated receptor-2 (PAR-2), expressed on keratinocytes but not on melanocytes, is involved in melanosome uptake via phagocytosis, and modulation of PAR-2 activation affects skin color. The pattern of melanosome distribution within the epidermis is skin color-dependent. In vitro, this distribution pattern is regulated by the ethnic origin of the keratinocytes, not the melanocytes. Therefore, we hypothesized that PAR-2 may play a role in the modulation of pigmentation in a skin type-dependent manner. We examined the expression of PAR-2 and its activator, trypsin, in human skins with different pigmentary levels. Here we show that PAR-2 and trypsin are expressed in higher levels, and are differentially localized in highly pigmented, relative to lightly pigmented skins. Moreover, highly pigmented skins exhibit an increase in PAR-2-specific protease cleavage ability. Microsphere phagocytosis was more efficient in keratinocytes from highly pigmented skins, and PAR-2 induced phagocytosis resulted in more efficient microsphere ingestion and more compacted microsphere organization in dark skin-derived keratinocytes. These results demonstrate that PAR-2 expression and activity correlate with skin color, suggesting the involvement of PAR-2 in ethnic skin color phenotypes.

Cytoprotective signaling by activated protein C requires protease-activated receptor-3 in podocytes

PubMed Central

Madhusudhan, Thati; Wang, Hongjie; Straub, Beate K.; Gröne, Elisabeth; Zhou, Qianxing; Shahzad, Khurrum; Müller-Krebs, Sandra; Schwenger, Vedat; Gerlitz, Bruce; Grinnell, Brian W.; Griffin, John H.; Reiser, Jochen; Gröne, Hermann-Josef; Esmon, Charles T.; Nawroth, Peter P.

2012-01-01

The cytoprotective effects of activated protein C (aPC) are well established. In contrast, the receptors and signaling mechanism through which aPC conveys cytoprotection in various cell types remain incompletely defined. Thus, within the renal glomeruli, aPC preserves endothelial cells via a protease-activated receptor-1 (PAR-1) and endothelial protein C receptor-dependent mechanism. Conversely, the signaling mechanism through which aPC protects podocytes remains unknown. While exploring the latter, we identified a novel aPC/PAR-dependent cytoprotective signaling mechanism. In podocytes, aPC inhibits apoptosis through proteolytic activation of PAR-3 independent of endothelial protein C receptor. PAR-3 is not signaling competent itself as it requires aPCinduced heterodimerization with PAR-2 (human podocytes) or PAR-1 (mouse podocytes). This cytoprotective signaling mechanism depends on caveolin-1 dephosphorylation. In vivo aPC protects against lipopolysaccharide-induced podocyte injury and proteinuria. Genetic deletion of PAR-3 impairs the nephroprotective effect of aPC, demonstrating the crucial role of PAR-3 for aPC-dependent podocyte protection. This novel, aPC-mediated interaction of PARs demonstrates the plasticity and cell-specificity of cytoprotective aPC signaling. The evidence of specific, dynamic signaling complexes underlying aPC-mediated cytoprotection may allow the design of cell type specific targeted therapies. PMID:22117049

Par Pond vegetation status Summer 1995 -- Summary

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

Mackey, H.E. Jr.; Riley, R.S.

1996-01-01

The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the newly emergent, shoreline aquatic plant communities of Par Pond began in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level. These surveys continued in July, September, and late October, 1995. Communities similar tomore » the pre-drawdown, Par Pond aquatic plant communities are becoming re-established. Emergent beds of maidencane, lotus, waterlily, and watershield are extensive and well developed. Cattail occurrence continued to increase during the summer, but large beds common to Par Pond prior to the drawdown have not formed. Estimates from SPOT HRV, remote sensing satellite data indicated that as much as 120 hectares of emergent wetlands vegetation may have been present along the Par Pond shoreline by early October, 1995. To track the continued development of macrophytes in Par Pond, future surveys throughout 1996 and 1997, along with the continued evaluation of satellite data to map the areal extent of the macrophyte beds of Par Pond, are planned.« less

Flow cytometry analysis reveals different activation profiles of thrombin- or TRAP-stimulated platelets in db/db mice. The regulatory role of PAR-3.

PubMed

Kassassir, Hassan; Siewiera, Karolina; Talar, Marcin; Przygodzki, Tomasz; Watala, Cezary

2017-06-01

Recent studies have shown that it may be the concentration of thrombin, which is discriminative in determining of the mechanism of platelet activation via protease activated receptors (PARs). Whether the observed phenomenon of differentiated responses of mouse platelets to various thrombin concentrations in non-diabetic db/+ and diabetic db/db mice depends upon the concerted action of various PARs, remains to be established. We found elevated reactivity of platelets, as well as the enhanced PAR-3 expression in response to both the used concentrations of AYPGKF in db/db mice, as compared to db/+ heterozygotes. At low concentration of thrombin platelets from diabetic mice demonstrated hyperreactivity, reflected by higher expression of PAR-3. For higher thrombin concentration, blood platelets from db/db mice appeared hyporeactive, compared to db/+ animals, while no significant differences in PAR-3 expression were observed between diabetic and non-diabetic mice. The novel and previously unreported finding resulting from our study is that the increased expression of PAR-3 in response to either TRAP for PAR-4 or low thrombin (when PAR-4 is not the efficient thrombin receptor) may be one of the key events contributing to higher reactivity of platelets in db/db mice. Copyright © 2017 Elsevier Inc. All rights reserved.