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Biomedical subjects

L A Collins

Publications and source records attributed to L A Collins.

At least 19 recordsLinked to original sources

Attosecond pump probe: exploring ultrafast electron motion inside an atom.

The attosecond pump probe, in close analogy to the standard femtosecond probing technique, has been proposed and theoretically demonstrated with its application to explore ultrafast electron motions inside atoms. We have performed realistic modeling for the full dynamics of both the femtosecond pumping and the attosecond probing processes. Our simulations have illustrated that an ultrashort oscillation period of 2.0 fs can be mapped out for a wave packet in low-lying excited states of the helium atom. This opens the prospect of a wealth of similar pump probe experiments to examine ultrafast electronic or atomic motions.

Journal Article↗

Molecular-dynamics simulations of cold antihydrogen formation in strongly magnetized plasmas.

Employing a high-order symplectic integrator and an adaptive time-step algorithm, we perform molecular-dynamics simulations of antihydrogen formation, in a cold plasma confined by a strong magnetic field, over time scales of microseconds. Sufficient positron-antiproton recombination events occur to allow a statistical analysis for various properties of the formed antihydrogen atoms. Giant-dipole states are formed in the initial stage of recombination. In addition to neutral atoms, we also observe antihydrogen positive ions (H(+)), in which two positrons simultaneously bind to an antiproton.

Journal Article↗

Imaging molecular structures by electron diffraction using an intense few-cycle pulse.

As an intense few-cycle pulse interacts with an atomic or molecular target, its strong oscillating field may first pull electrons out of the target and subsequently drive them back to scatter on the target. The scattering may occur only a few times or even once during the interaction. This unique property of few-cycle pulses enables one to image ultrafast transient structures of matter by the means of pulse-driven electron diffraction. We demonstrated this phenomenon with K(+)(2) via three-dimensional calculations of the time-dependent Schro dinger equation.

Journal Article↗

Simulations of the optical properties of warm dense aluminum.

Using quantum molecular dynamics simulations, we show that the optical properties of aluminum change drastically along the nonmetal metal transition observed experimentally. As the density increases and the many-body effects become important, the optical response gradually evolves from the one characteristic of an atomic fluid to the one of a simple metal. We show that quantum molecular dynamics combined with the Kubo-Greenwood formulation naturally embodies the two limits and provides a powerful tool to calculate and benchmark the optical properties of various systems as they evolve into the warm dense matter regime.

Journal Article↗

Electrical conductivity for warm, dense aluminum plasmas and liquids.

The electrical conductivity of warm, dense aluminum plasmas and liquids is calculated using ab initio molecular dynamics and the Kubo-Greenwood formula. The density range extends from near solid to one-hundredth of solid density, and the temperature range extends from 6000 K to 30 000 K. This density and temperature range allows direct comparison with experimental results obtained with the tamped exploding wire technique.

Journal Article↗

Evolution of ultracold neutral plasmas.

We present the first large-scale simulations of an ultracold neutral plasma, produced by photoionization of laser-cooled xenon atoms, from creation to initial expansion, using classical molecular-dynamics methods with open boundary conditions. We reproduce many of the experimental findings such as the trapping efficiency of electrons with increased ion number, a minimum electron temperature achieved on approach to the photoionization threshold, and recombination into Rydberg states of an anomalously low principal quantum number. In addition, many of these effects establish themselves very early in the plasma evolution ( similar ns) before the present experimental observations begin.

Journal Article↗

Calculation of a deuterium double shock Hugoniot from ab initio simulations.

We calculate the equation of state of dense deuterium with two ab initio simulation techniques, path integral Monte Carlo and density functional theory molecular dynamics, in the density range of 0.67 < or = rho < or = 1.60 g cm(-3). We derive the double shock Hugoniot and compare with the recent laser-driven double shock wave experiments by Mostovych et al. [Phys. Rev. Lett. 85, 3870 (2000)]. We find excellent agreement between the two types of microscopic simulations, but a significant discrepancy with the laser-driven shock measurements.

Journal Article↗

Watching dark solitons decay into vortex rings in a Bose-Einstein condensate.

We have created spatial dark solitons in two-component Bose-Einstein condensates in which the soliton exists in one of the condensate components and the soliton nodal plane is filled with the second component. The filled solitons are stable for hundreds of milliseconds. The filling can be selectively removed, making the soliton more susceptible to dynamical instabilities. For a condensate in a spherically symmetric potential, these instabilities cause the dark soliton to decay into stable vortex rings. We have imaged the resulting vortex rings.

Journal Article↗

Simulations of fluid hydrogen: comparison of a dissociation model with tight-binding molecular dynamics.

We compare the results of two complementary approaches, tight-binding molecular-dynamics simulations and a dissociation model, for determining the characteristics of dense, fluid hydrogen at pressures extending to megabars and temperatures to 10 000 K. Two tight-binding models were examined: one parametrization emphasized crystalline, molecular, and fluid properties, the other focused more on the intricate molecular interactions involving up to four hydrogen atoms. The two tight-binding cases and the dissociation model agree reasonably well for a variety of properties, including the equation of state, dissociation degree, and proton pair-correlation functions. In simulations of recently reported laser-driven shock experiments, the tight-binding and dissociative models predict different maximum compressions of four and five, respectively. We discuss the sensitivities of the models as well as give estimates for the region of validity of the chemical picture (dissociation model) and the accuracy of the dynamical picture (tight-binding simulations) in cases where molecular hydrogen still dominates the physical behavior.

Journal Article↗

Green fluorescent protein reporter microplate assay for high-throughput screening of compounds against Mycobacterium tuberculosis.

An optimal assay for high-throughput screening for new antituberculosis agents would combine the microplate format and low cost of firefly luciferase reporter assays and redox dyes with the ease of kinetic monitoring inherent in the BACTEC system. The green fluorescent protein (GFP) of the jellyfish Aequorea victoria is a useful reporter molecule which requires neither substrates nor cofactors due to the intrinsically fluorescent nature of the protein. The gene encoding a red-shifted, higher-intensity GFP variant was introduced by electroporation into Mycobacterium tuberculosis H37Ra and M. tuberculosis H37Rv on expression vector pFPV2. A microplate-based fluorescence assay (GFP microplate assay [GFPMA]) was developed and evaluated by determining the MICs of existing antimycobacterial agents. The MICs of isoniazid, rifampin, ethambutol, streptomycin, amikacin, ofloxacin, ethionamide, thiacetazone, and capreomycin, but not cycloserine, determined by GFPMA were within 1 log2 dilution of those determined with the BACTEC 460 system and were available in 7 days. Equivalent MICs of antituberculosis agents in the BACTEC 460 system for both the reporter and parent strains suggested that introduction of pFPV2 did not influence drug susceptibility, in general. GFPMA provides a unique tool with which the dynamic response of M. tuberculosis to the existing and potential antituberculosis agents can easily, rapidly, and inexpensively be monitored.

Anti-Infective Agents↗

Sympathetic nervous system in salt-sensitive and obese hypertension: amelioration of multiple abnormalities by a central sympatholytic agent.

Excess activity of the sympathetic nervous system (SNS) is linked to human obese hypertension and to salt-sensitive hypertension. Paradoxically, reduced SNS activity has been implicated as a contributor to obesity, particularly in animal models, and salt loading usually inhibits SNS activity. We have investigated the relationship between SNS activity, diet, and hypertension in the obese spontaneously hypertensive rat (SHROB), a model with a recessive obesity trait superimposed on a hypertensive background with multiple metabolic abnormalities resembling human syndrome X. We examined the role of SNS overactivity in the adverse impact of excess dietary salt and the possible beneficial effects of sympatholytic therapy. Mean blood pressure (MBP) was increased in SHROB and SHR fed a 4% NaCl diet. The pressor effect of dietary salt was abolished by ganglionic blockade, suggesting that increased SNS activity contributed to the pressor effect of the high-salt diet. Moxonidine, a second-generation central antihypertensive, controlled hypertension in both SHROB and SHR. Kidney damage in SHROB was accelerated by dietary salt and was reduced by moxonidine. Moxonidine elicited progressive weight loss in SHROB but not in SHR. Food intake in SHROB was reduced to the level of lean SHR. SHROB and SHR treated with moxonidine showed improved glucose tolerance. Additionally, SHROB showed reduced levels of triglycerides, cholesterol, and insulin following moxonidine therapy. Inhibition of the SNS, as with moxonidine therapy, may ameliorate multiple abnormalities and have therapeutic advantages in obese hypertensive syndromes.

Animals↗

Development of a Defined Minimal Medium for the Growth of Edwardsiella ictaluri.

In this report, a complete defined medium and a minimally defined medium are described for Edwardsiella ictaluri. The complete defined medium consists of 46 individual components, including a basal salt solution, glucose, magnesium sulfate, iron sulfate, six trace metals, four nucleotides, 10 vitamins, and 19 amino acids. This medium supports growth in broth and on solid media. Optimal growth at 30(deg)C was obtained at pH 7.0, and at an osmolality of 390 mosmol/kg of H(inf2)O, with a glucose concentration of 4 g/liter. The defined minimal medium reduces the 46 components of the complete medium to eight essential components, including the basal salt solution, glucose, magnesium sulfate, pantothenic acid, and niacinamide. In addition, specific amino acids that depend on the specific requirements of the individual strains of E. ictaluri are added.

Journal Article↗

Consequences of weight cycling in obese spontaneously hypertensive rats.

We mimicked human weight cycling in the obese spontaneously hypertensive rat (SHROB) model of genetic obesity. A 12-day very low calorie diet (VLCD; 16.7% of baseline calories) was alternated with 4-6 wk of ad libitum chow refeeding for three cycles. Control SHROB ate chow ad libitum. VLCD induced rapid weight loss, but during refeeding all the lost weight was regained. Final body weight was higher in cycled rats than in ad libitum controls (149 +/- 5 vs. 117 +/- 7% of initial baseline). Less weight was lost as a percent of starting body weight during each successive VLCD, which could not be explained by aging. At death, retroperitoneal fat pads were heavier in cycled SHROB than in ad libitum controls (62 +/- 3 vs. 44 +/- 4 g). During the first 2 days after each VLCD, cycled rats overate significantly relative to ad libitum controls (88 +/- 2 vs. 78 +/- 3 kcal/day), but cumulative food intake throughout the duration of the experiment did not differ (11.4 +/- 0.6 vs. 11.7 +/- 0.1 Mcal). Compared with ad libitum-fed rats, food efficiency (g body wt gain/kcal) was increased during each refeeding period. Weight cycling elevated blood pressure above the initial baseline throughout refeeding. Refeeding hypertension was abolished by ganglionic blockade with chlorisondamine. Thus weight cycling in SHROB exacerbates obesity, metabolic efficiency, abdominal fat accumulation, sympathetic activity, and hypertension.

Adipose Tissue↗

I1-imidazoline receptors. Definition, characterization, distribution, and transmembrane signaling.

Data were presented showing that I1-imidazoline sites show a unique ligand specificity that differs markedly from that of any of the alpha 2-adrenergic subtypes or the I2-imidazoline sites labeled by [3H]idazoxan. On the other hand, the ligand specificity of I1-imidazoline sites is maintained across mammalian species (cow, rat, dog, and human) and between different tissues and cell types. I1-Imidazoline sites can be further distinguished from I2 sites because the latter, unlike I1 sites, were not present in RVLM membranes from bovine brain stem. Furthermore, I1-imidazoline sites were modulated by guanine nucleotides with a specificity appropriate for a receptor coupled to G-protein and were mainly localized to plasma membranes. I1-Imidazoline sites show a unique pattern of distribution between diverse tissues and cell types and appear to be a neuroepithelial marker as well as being present in secretory cells of the pancreatic islets. The widespread distribution of I1-imidazoline sites implies that the functional significance of this putative receptor may have been underestimated. The signaling pathway associated with the I1-imidazoline receptor remains to be fully elucidated, but is likely that activation of phospholipase A2 leading to release of arachidonic acid and subsequent generation of prostaglandins plays a major role.

Animals↗

Effect of I1-imidazoline receptor activation on responses of hypoglossal and phrenic nerve to chemical stimulation.

Sedation elicited by some centrally acting antihypertensive agents may interfere with respiratory control, and by selectively inhibiting upper airway dilating muscle activity it may facilitate obstructive sleep apnea. Autoradiographic studies with [125I]p-iodoclonidine in the presence of 10 microM epinephrine to block alpha 2-adrenergic sites or 100 nM moxonidine to mask I1-imidazoline sites show that both I1- as well as alpha 2-sites are localized in putative chemosensory areas of the rostral ventrolateral medulla in the cat. We sought to determine the effect of activating I1 and alpha 2-receptors on central chemosensitivity by using moxonidine as a selective I1 agonist, clonidine as a mixed I1/alpha 2 agonist, SK&F-86466 as a specific alpha 2-antagonist, and efaroxan as a mixed I1/alpha 2 antagonist. We recorded responses of phrenic, hypoglossal, and cervical sympathetic nerve activities to progressive hypercapnia after hyperventilation to apnea. Moxonidine (3-100 micrograms/kg i.v.) caused dose-dependent decreases in tonic cervical sympathetic nerve activity and blood pressure, but had no effect on the CO2 threshold (after 30 or 100 micrograms/kg moxonidine, phrenic nerve activity reappeared at 5.8 +/- 0.2% CO2 versus 5.6 +/- 0.3% CO2 in control). Following moxonidine, the slope of the steep portion of the CO2 response tended to increase (10.3 +/- 1.8 versus 7.3 +/- 0.9). Peak phrenic nerve activity was comparable to control at 7.5% CO2 (20 +/- 2 U in control) and at 9.5% CO2 (30 +/- 3 versus 27. +/- 2 U). Similarly, the response of hypoglossal and inspiratory phasic cervical sympathetic nerve activity to a progressive CO2 rise was not affected by moxonidine. By contrast, clonidine in the same doses decreased CO2 sensitivity, because the CO2 threshold was elevated from 5.3 +/- 0.5% to 6.7 +/- 0.4% (p < 0.001). The slope of the CO2 response was decreased from 9.7 +/- 1.9 to 7.4 +/- 1.3 (p = 0.05). Peak phrenic nerve activity was reduced at 7.5% CO2 (11 +/- 5 versus 25 +/- 2 U; p < 0.05) and at 9.5% CO2 (21 +/- 4 versus 33 +/- 2 U; p = 0.06). Clonidine selectively inhibited the response of hypoglossal nerve activity to CO2. The depressive effects of clonidine were reversed by alpha 2-blockade with SK&F-86466 (0.5 or 1 mg/kg). Inspiratory phasic cervical sympathetic nerve activity increased after SK&F-86466 in parallel with phrenic and hypoglossal nerve activity, but the tonic component of cervical sympathetic nerve activity and blood pressure increased only transiently.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic alpha-2 Receptor Antagonists↗

A novel mechanism of action for hypertension control: moxonidine as a selective I1-imidazoline agonist.

Sympathoadrenal inhibition by a direct action within the central nervous system is an advantageous route to blood pressure control. Stimulation of brain alpha 2-adrenergic receptors is one mechanism for sympathoadrenal suppression, but comes at the cost of nonspecific depression of CNS function, including sedation and decreased salivary flow. Evidence is accumulating for a second pathway for pharmacological control of sympathoadrenal outflow, mediated by a novel receptor specific for imidazolines. First-generation central antihypertensive agents, which are imidazolines such as clonidine, act primarily to stimulate these I1-imidazoline receptors in the rostral ventrolateral medulla oblongata (RVLM) to lower blood pressure, but have sufficient agonism at alpha 2-adrenergic receptors to produce side effects. Second-generation centrally acting antihypertensive agents, such as moxonidine and rilmenidine, are selective for I1 relative to alpha 2 receptors. The reduced alpha 2 potency of these agents correlates with reduced severity of side effects. In this study we further established the selectivity of moxonidine for I1-imidazoline sites by characterizing the direct interaction of [3H]moxonidine with these receptors in the RVLM and in adrenomedullary chromaffin cells. [3H]Moxonidine preferentially labeled I1-imidazoline sites relative to alpha 2-adrenergic sites, only a small portion of which were labeled in the RVLM. [3H]Moxonidine binding to I1-imidazoline sites was modulated by guanine nucleotides, implying that I1-imidazoline sites may be membrane receptors coupled to guanine nucleotide binding regulatory proteins (G proteins). Receptor autoradiography with [125I]p-iodoclonidine confirmed the presence of I1-imidazoline sites in the RVLM and other areas of the brainstem reticular formation. In contrast, alpha 2-adrenergic sites were mainly localized to the nucleus of the solitary tract. Moxonidine selectively displaced [125I]p-iodoclonidine binding from reticular areas, including the RVLM. In vivo studies in SHR rats confirmed the ability of moxonidine to normalize hypertension by an action within the RVLM and confirmed the correspondence of I1 binding affinity and antihypertensive efficacy. We also discuss prior literature on the cardiovascular pharmacology of imidazolines, reinterpreting previous studies that only considered alpha-adrenergic mechanisms.

Adrenal Medulla↗

Comparative activities of piperacillin and tazobactam against clinical isolates of Legionella spp.

We evaluated the in vitro activity of piperacillin alone or in combination with the beta-lactamase inhibitor tazobactam against clinical isolates of Legionella species. At an inoculum of approximately 10(4) CFU, tazobactam, piperacillin, and the 8:1 combination had equivalent activities against Legionella spp. At an approximately 10-fold higher inoculum, the following results were obtained, expressed as MICs for 50 and 90% of strains tested (MIC range): piperacillin, 4 and 16 (0.25 to 32) micrograms/ml; tazobactam, 0.5 and 1 (0.125 to 2) micrograms/ml; and piperacillin-tazobactam (expressed in terms of MIC of piperacillin) 0.5 and 1 (0.03 to 2) micrograms/ml. Tazobactam alone and the combination with piperacillin were more active than piperacillin alone at the higher inoculum.

Drug Synergism↗