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Biomedical subjects

Y T Li

Publications and source records attributed to Y T Li.

At least 19 recordsLinked to original sources

Observation of a fast electron beam emitted along the surface of a target irradiated by intense femtosecond laser pulses.

A novel fast electron beam emitting along the surface of a target irradiated by intense laser pulses is observed. The beam is found to appear only when the plasma density scale length is small. Numerical simulations reveal that the electron beam is formed due to the confinement of the surface quasistatic electromagnetic fields. The results are of interest for potential applications of fast electron beams and deep understanding of the cone-target physics in the fast ignition related experiments.

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Demonstration of bulk acceleration of ions in ultraintense laser interactions with low-density foams.

Ion acceleration inside low-density foams irradiated by ultraintense laser pulses has been studied experimentally and theoretically. It is found that the ion generation is closely correlated with the suppressed hot electron transport inside the foams. Particle-in-cell simulations suggest that localized electrostatic fields with multi peaks around the surfaces of lamellar layers inside the foams are induced. These fields inhibit hot electron transport and meanwhile accelerate ions inside the foams, forming a bulk acceleration in contrast to the surface acceleration at the front and rear sides of a thin solid target.

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Thomson scattering measurements of heat flux from ion-acoustic waves in laser-produced aluminum plasmas.

Thomson scattering (TS) measurements are performed at different locations in a laser-produced aluminum plasma. Variations of the separation, wavelength shift, and asymmetric distribution of the two ion-acoustic waves are investigated from their spectral-time-resolved TS images. Detailed information on the space-time evolution of the plasma parameters is obtained. Electron distribution and variation of the heat flux in the plasma are also obtained for a steep temperature gradient.

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Emission direction of fast electrons in laser-solid interactions at intensities from the nonrelativistic to the relativistic.

The emission direction of outward-ejecting fast electrons generated in laser-solid interactions by 30 fs laser pulses is measured for laser intensities varying from the nonrelativistic to the relativistic. For an s-polarized incident laser beam at nonrelativistic intensities, the ejected electrons are close to the polarization direction of the laser beam. With the increase of the laser intensity, the ejected electrons are still mainly within the polarization plane, but turn away from the laser polarization direction towards the opposite direction of the incident laser beam. At relativistic intensities, electrons eject towards the direction of the reflected laser beam. The increasing ponderomotive force acceleration with the laser intensities might be responsible for the observed changes.

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High-energy electrons produced in subpicosecond laser-plasma interactions from subrelativistic laser intensities to relativistic intensities.

The characteristics of the forward hot electrons produced by subpicosecond laser-plasma interactions are studied for different laser polarizations at laser intensities from subrelativistic to relativistic. The peak of the hot electron beam produced by p-polarized laser beam shifts to the laser propagation direction from the target normal direction as the laser intensity reaches the relativistic. For s-polarized laser pulse, hot electrons are mainly directed to the laser axis direction. The temperature and the maximum energy of hot electrons are much higher than that expected by the empirical scaling law. The energy spectra of the hot electrons evolve to be a single-temperature structure at relativistic laser intensities from the two-temperature structure at subrelativistic intensities. For relativistic laser intensities, the forward hot electrons are less dependent on the laser polarization under the laser conditions. The existing of a preplasma formed by the laser amplified spontaneous emission pedestal plays an important role in the interaction. One-dimensional particle-in-cell simulations reproduce the most characteristics observed in the experiment.

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Energetic electrons emitted from ethanol droplets irradiated by femtosecond laser pulses.

We investigate the angular distribution and the energy spectrum of hot electrons emitted from ethanol droplets irradiated by linearly polarized 150-fs laser pulses at an intensity of 10(16) W/cm(2). Two hot electron jets symmetrically with respect to the laser propagation direction are observed within the polarization plane. This is due to the spherical geometry of droplets in the intense laser field. The maximum energy of the hot electrons is found to be more than 600 keV. Particle-in-cell simulations suggest that the resonance absorption is the main mechanism for hot electron generation.

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Blast waves produced by interactions of femtosecond laser pulses with water.

The behaviors of the blast waves produced by femtosecond laser-water interactions, and the blast waves induced by laser self-focusing in air, have been investigated using optical shadowgraphy at a maximum intensity of 1 x 10(16) W/cm(2). The temporal evolution of the blast wave launched by the water plasma can be described by a planar blast wave model including source mass. An aneurismlike structure, due to the quick propagation inside a hollow channel formed by laser self-focusing, is observed. The expansion of the channel in air is found to agree with a cylindrical self-similar blast wave solution.

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Spatial distribution of high-energy electron emission from water plasmas produced by femtosecond laser pulses.

High energy electrons emitted by water plasmas produced by a single or a multiple laser pulse are investigated. The multipulse mode greatly enhances the generation and the temperature of hot electrons. Directional emission of high energy electrons over 25 keV is observed in two symmetric directions with respect to the laser axis and at 46 degrees from the directions of the laser electric field. Two-dimensional particle-in-cell simulations reproduce well the experimental results and indicate that the acceleration mechanism of the high energy electrons is due mainly to the resonance absorption at the edge of the spherical droplets formed by the leading pulse.

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Propagation of hot electrons through high-density plasmas.

Propagation of hot electrons through high-density plasmas generated by femtosecond laser pulses is investigated using three types of target configurations: Al-coated glass, Al and glass separated by a vacuum gap, and Al foil alone. Collimated ionization tracks lasting for 60 ps and extending 150-300 microm in length and 8 microm in cross section are observed via optical probing. For the Al-foil-alone target, a narrow plasma jet is formed at the rear surface in line with the laser. The collimation of the hot electrons may be attributed to a strong self-generated magnetic field in the target.

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Third-order harmonic generation by self-guided femtosecond pulses in air.

Strong third-order harmonic (TH) emission is observed with a conversion efficiency higher than 10(-3) from a plasma channel formed by self-guided femtosecond laser pulses propagating in air. The main characteristics of TH emission in various conditions and the phase-matching condition between the fundamental and the TH wave are investigated. An optimized condition is found, under which the TH conversion efficiency is maximized. Our experimental results show that radiation of the emission in ultraviolet wavelength range makes a major attribution to TH emission, whereas the effects of self-phase modulation are not important when intense laser pulses interact with gaseous media.

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ATTEMPTS: a heparin/protamine-based delivery system for enzyme drugs.

A prodrug delivery system termed "Antibody Targeted, Triggered, Electrically Modified Prodrug-Type Strategy (ATTEMPTS)" has been developed to permit the antibody-directed administration of inactive enzyme drug including tissue-type plasminogen activator (tPA), and allow a subsequent triggered release of the active tPA at the target site. Cation-modified tPA (mtPA) was attached to a heparin-antifibrin complex via ionic interaction, and the active tPA can subsequently be released by the addition of protamine, a competitive heparin inhibitor. Anti-fibrin IgG was conjugated to heparin via an end-point attachment to form the heparin-antifibrin complex which provides the targeting efficiency of the final heparin/mtPA complex. Cation modification was performed by either chemical conjugation by linking (Arg)7Cys to tPA with N-succinimidy-3-(2-pyridyldithio) propionate or by recombinant DNA methods. Results show that the modification process did not significantly alter the specific activity of tPA with regard to plasminogen activation, fibrin-binding ability, and response toward fibrinogen. The complexes of both modified tPA-heparin did not yield any intrinsic catalytic activity owing to the blockage of the active site of tPA by the attached heparin. On the other hand, heparin-induced inhibition of modified tPA activity was reversed by adding protamine, which is similar to that of a prodrug delivery system. These results suggest that heparin/protamine-based enzyme delivery systems may be a useful tool to improve current enzyme therapeutic status, as well as thrombolytic therapy, by both regulating the release of active enzyme and aborting the associated systemic toxic effect. Currently, modification of enzyme drugs has been optimized by recombinant DNA technology assisted by computer simulation. In addition, the original strategy has been revised to obtain enhanced therapeutic efficacy.

Base Sequence↗

Degradation of G(M1) and G(M2) by mammalian sialidases.

In mammalian tissues, the pathway known for the catabolism of G(M1) [Galbeta3GalNAcbeta4(Neu5Acalpha3)Galbeta4GlcCer; where Cer is ceramide] is the conversion of this ganglioside into G(M2) [GalNAcbeta4(Neu5Acalpha3)Galbeta4GlcbetaCer] by beta-galactosidase followed by the conversion of G(M2) into G(M3) (Neu5Acalpha3Galbeta4GlcbetaCer) by beta-N-acetylhexosaminidase A (Hex A). However, the question of whether or not G(M1) and G(M2) can also be respectively converted into asialo-G(M1) (Galbeta3GalNAcbeta4Galbeta4GlcCer; G(A1)) and asialo-G(M2) (GalNAcbeta4Galbeta4GlcbetaCer, G(A2)) by mammalian sialidases has not been resolved. This is due to the fact that sialidases purified from mammalian tissues always contained detergents that interfered with the in vitro hydrolysis of G(M1) and G(M2) in the presence of an activator protein. The mouse model of human type B Tay-Sachs disease created by the disruption of the Hexa gene showed no neurological abnormalities, with milder clinical symptoms than the human counterpart, and the accumulation of G(M2) in the brains of affected mice was only limited to certain regions [Sango, Yamanaka, Hoffmann, Okuda, Grinberg, Westphal, McDonald, Crawley, Sandhoff, Suzuki and Proia (1995) Nat. Genet. 11, 170-176]. These results suggest the possible presence of an alternative catabolic pathway (the G(A2) pathway) in mouse to convert G(M2) into G(A2) by sialidase. To show the existence of this pathway, we have used recombinant mammalian cytosolic sialidase and membrane-associated sialidase to study the desialylation of G(M1) and G(M2). We found that the mouse membrane-bound sialidase was able to convert G(M1) and G(M2) into their respective asialo-derivatives in the presence of human or mouse G(M2) activator protein. The cytosolic sialidase did not exhibit this activity. Our results suggest that, in vivo, the stable NeuAc of G(M1) and G(M2) may be removed by the mammalian membrane-associated sialidase in the presence of G(M2) activator protein. They also support the presence of the G(A2) pathway for the catabolism of G(M2) in mouse.

Animals↗

Effects of laser polarization on jet emission of fast electrons in femtosecond-laser plasmas.

Effects of laser polarization on fast electron emission are studied from an aluminum target irradiated by ultrashort laser pulses at 2 x 10(16) W/cm(2). Jet emission of outgoing fast electrons collimated in the polarization direction is observed for s-polarized laser irradiation, whereas for p-polarized irradiation highly directional emission of outgoing fast electrons is found in the direction close to the normal of the target. The behavior of ingoing fast electrons into the target for s- and p-polarized irradiation is also investigated by observing x-ray bremsstrahlung radiation at the backside of the target.

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Hot electrons in the interaction of femtosecond laser pulses with foil targets at a moderate laser intensity.

Characteristics of hot electrons produced in the interaction of femtosecond laser pulses with foil targets were investigated at a moderate laser intensity. Both outgoing and ingoing hot electrons from the femtosecond laser plasma were studied. A collimated jet of outgoing hot electrons was observed in the target normal direction. An ingoing energetic hot-electron beam was found in the laser propagation direction, while the low-energy ingoing electrons spread into wider cone angle due to the collisional effects in the plasma and target material. These observations were supported by three-dimensional Monte Carlo simulations. The hot-electron temperature obtained from electron spectra and absorption experiments implies that resonance absorption is partially responsible for the generation of hot electrons.

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A novel endo-beta-galactosidase from Clostridium perfringens that liberates the disaccharide GlcNAcalpha 1-->Gal from glycans specifically expressed in the gastric gland mucous cell-type mucin.

We found that commercially available sialidases prepared from Clostridium perfringens ATCC10543 were contaminated with an endoglycosidase capable of releasing the disaccharide GlcNAcalpha1-->4Gal from glycans expressed in the gastric gland mucous cell-type mucin. We have isolated this enzyme in electrophoretically homogeneous form from the culture supernatant of this organism by ammonium sulfate precipitation followed by affinity chromatography using a Sephacryl S-200 HR column. The enzyme was specifically retained by and eluted from the column with methyl-alpha-Glc. By NMR spectroscopy, the structure of the disaccharide released from porcine gastric mucin by this enzyme was established to be GlcNAcalpha1-->4Gal. The specificity of this enzyme as an endo-beta-galactosidase was established by analyzing the liberation of GlcNAcalpha1-->4Gal from GlcNAcalpha1-->4Galbeta1-->4GlcNAcbeta1-->6(GlcNAcalpha1--> 4Galbeta1-->3)GalNAc-ol by mass spectrometry. Because this novel endo-beta-galactosidase specifically releases the GlcNAcalpha1-->4Gal moiety from porcine gastric mucin, we propose to call this enzyme a GlcNAcalpha1-->4Gal-releasing endo-beta-galactosidase (Endo-beta-Gal(GnGa)). Endo-beta-Gal(GnGa) was found to remove the GlcNAcalpha1-->4Gal epitope expressed in gastric adenocarcinoma AGS cells transfected with alpha1,4-N-acetylglucosaminyltransferase cDNA. Endo-beta-Gal(GnGa) should become useful for studying the structure and function of glycoconjugates containing the terminal GlcNAcalpha1-->4Gal epitope.

Adenocarcinoma↗

ATTEMPTS: a heparin/protamine-based prodrug approach for delivery of thrombolytic drugs.

The aim of this study is to develop a heparin/protamine-based prodrug system for the controlled delivery of enzyme such as tissue-type plasminogen activator (tPA). This approach, termed antibody targeted, triggered, electrically modified prodrug-type strategy (ATTEMPTS), would permit antibody-directed administration of inactive tPA, and allow a subsequent triggered release of the active tPA at the target site. Cation-modified tPA (mtPA) was attached to a heparin--antifibrin complex via ionic interaction. The active tPA can be subsequently released by the addition of protamine, a competitive heparin inhibitor. Anti-fibrin IgG was conjugated to heparin via an end-point attachment to form the heparin--antifibrin--complex which provides the targeting efficiency of the final heparin--mtPA complex. Cation-modification was performed either by chemical conjugation by linking (Arg)(7)Cys to tPA with N-succinimidy-3-(2-pyridyldithio) propionate or by recombinant DNA method. Results show that the chemical modification process did not significantly alter specific activity of tPA with regard to plasminogen activation, fibrin-binding ability, and response toward fibrinogen. Expressed modified tPA (EmtPA) produced by recombinant DNA methods retained the same catalytic activity of the parent tPA, as well as a dynamic catalytic behavior depending upon the presence of heparin and protamine. Both types of modified tPA, especially the mtPA demonstrated a significantly higher affinity toward heparin or heparin--antifibrin complex than native tPA. In addition, the complexes of mtPA--heparin did not yield any intrinsic clot lysis activity owing to the blockage of the active site of tPA by attached heparin. On the other hand, heparin-induced inhibition of both mtPA and EmtPA activity was reversed by adding protamine, as confirmed by chromogenic and in vitro clot lysis assays. These results suggested that a heparin/protamine-based tPA delivery system may be a useful tool to improve current thrombolytic therapeutic status, by both precisely regulating the release of active tPA and aborting the associated bleeding risk. Alternatively, this ATTEMPTS approach could also be used to deliver enzyme drugs while diminishing their associated toxic effects.

Antifibrinolytic Agents↗

A unique sialidase that cleaves the Neu5Gcalpha2-->5-O(glycolyl)Neu5Gc linkage: comparison of its specificity with that of three microbial sialidases toward four sialic acid dimers.

We found that the hepatopancreas of oyster, Crassostrea virginica, contained a sialidase capable of releasing Neu5Gc from the novel polysialic acid chain (-->5-O(glycolyl)Neu5Gcalpha2-->)n more efficiently than from the conventional type of polysialic acid chains, (-->8Neu5Acalpha2-->)n, or (-->8Neu5Gcalpha2-->)n. We have partially purified this novel sialidase and compared its reactivity with that of microbial sialidases using four different sialic acid dimers, Neu5Gcalpha2-->5-O(glycolyl)Neu5Gc (Gg2), Neu5Acalpha2-->8Neu5Ac (A2), Neu5Gcalpha2-->8Neu5Gc (G2), and KDNalpha2-->8KDN (K2) as substrates. Hydrolysis was monitored by high performance anion-exchange chromatography with a CarboPac PA-100 column and pulsed amperometric detection, the method by which we can accurately quantitate both the substrate (sialiac acid dimers) and the product (sialic acid monomers). The oyster sialidase effectively hydrolyzed Gg2 and K2, whereas A2 and G2 were poor substrates. Neu5Ac2en but not KDN2en effectively inhibited the hydrolysis of Gg2 by the oyster sialidase. Likewise, the hydrolysis of K2 by the oyster sialidase was inhibited by a cognate inhibitor, KDN2en, but not by Neu5Ac2en. Using the new analytical method we found that Gg2 was hydrolyzed less efficiently than A2 but much more readily than G2 by Arthrobacter ureafaciens sialidase. This result was at variance with the previous report using the thiobarbituric acid method to detect the released free sialic acid [Kitazume, S., et al. (1994) Biochem. Biophys. Res. Commun. 205, 893-898]. In agreement with previous results, Gg2 was a poor substrate for Clostridium perfringens sialidase, while K2 was refractory to all microbial sialidases tested. Thus, the oyster sialidase is novel and distinct from microbial sialidases with regards to glycon- and linkage-specificity. This finding adds an example of the presence of diverse sialidases, in line with the diverse sialic acids and sialic acid linkages that exist in nature. The new sialidase should become useful for both structural and functional studies of sialoglycoconjugates.

Animals↗