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At least 1,423 records · Page 79Linked to original sources
PubMed2000

Microtubule self-organization is gravity-dependent.

Although weightlessness is known to affect living cells, the manner by which this occurs is unknown. Some reaction-diffusion processes have been theoretically predicted as being gravity-dependent. Microtubules, a major constituent of the cellular cytoskeleton, self-organize in vitro by way of reaction-diffusion processes. To investigate how self-organization depends on gravity, microtubules were assembled under low gravity conditions produced during space flight. Contrary to the samples formed on an in-flight 1 x g centrifuge, the samples prepared in microgravity showed almost no self-organization and were locally disordered.

Animals↗
PubMed1993

Unconfined lateral diffusion and an estimate of pericellular matrix viscosity revealed by measuring the mobility of gold-tagged lipids.

Nanovid (video-enhanced) microscopy was used to determine whether lateral diffusion in the plasma membrane of colloidal gold-tagged lipid molecules is confined or is unrestricted. Confinement could be produced by domains within the plane of the plasma membrane or by filamentous barriers within the pericellular matrix. Fluorescein-phosphatidylethanolamine (F1-PE), incorporated into the plasma membranes of cultured fibroblasts, epithelial cells and keratocytes, was labeled with 30-nm colloidal gold conjugated to anti-fluorescein (anti-F1). The trajectories of the gold-labeled lipids were used to compute diffusion coefficients (DG) and to test for restricted motion. On the cell lamella, the gold-labeled lipids diffused freely in the plasma membrane. Since the gold must move through the pericellular matrix as the attached lipid diffuses in the plasma membrane, this result suggests that any extensive filamentous barriers in the pericellular matrix are at least 40 nm from the plasma membrane surface. The average diffusion coefficients ranged from 1.1 to 1.7 x 10(-9) cm2/s. These values were lower than the average diffusion coefficients (DF) (5.4 to 9.5 x 10(-9) cm2/s) obtained by FRAP. The lower DG is partially due to the pericellular matrix as demonstrated by the result that heparinase treatment of keratocytes significantly increased DG to 2.8 x 10(-9) cm2/s, but did not affect DF. Pericellular matrix viscosity was estimated from the frictional coefficients computed from DG and DF and ranged from 0.5 to 0.9 poise for untreated cells. Heparinase treatment of keratocytes decreased the apparent viscosity to approximately 0.1 poise. To evaluate the presence of domains or barriers, the trajectories and corresponding mean square displacement (MSD) plots of gold-labeled lipids were compared to the trajectories and MSD plots resulting from computer simulations of random walks within corrals. Based on these comparisons, we conclude that, if there are domains limiting the diffusion of F1-PE, most are larger than 5 microns in diameter.

Animals↗
PubMed2026

GAMMA: gap-aware motif mining under incomplete labeling with applications to MHC motifs.

MOTIVATION: Sequence motif identification is crucial for understanding molecular recognition, particularly in immune responses involving peptide binding to major histocompatibility complex (MHC) Class I molecules for antigen presentation to T cells. Traditionally, MHC Class I binding motifs are assumed to be contiguous and span nine amino acids. However, structural evidence suggests that binding may involve nonadjacent residues, challenging the assumptions of existing methods. RESULTS: In this study, we propose Gap-Aware Motif Mining Algorithm (GAMMA), a probabilistic framework designed to identify noncontiguous motifs under conditions of incomplete labeling. GAMMA employs Bayesian inference with Markov chain Monte Carlo sampling to jointly estimate motif parameters, binding locations, and the relative spacing between binding positions. Through extensive simulations and real-world applications to MHC Class I peptide datasets, GAMMA outperforms existing motif discovery tools such as GLAM2 in accurately localizing binding residues and identifying the underlying motifs. Notably, our results suggest that the true number of binding residues may be eight, fewer than the commonly assumed nine. In addition, for longer peptides, the model captures increased flexibility in the central region, consistent with structural observations that peptides may bulge in the middle. AVAILABILITY AND IMPLEMENTATION: The raw data and the source codes are available on GitHub (https://github.com/RanLIUaca/GAMMAmotif).

Amino Acid Motifs↗
PubMed1985

Mezlocillin, ceftizoxime, and amikacin alone and in combination against six Enterobacteriaceae in a neutropenic site in rabbits.

Closed-space, locally neutropaenic infection sites were simulated in rabbits by implanting subcutaneous semipermeable chambers inoculated with 5 X 10(4) cfu/ml of Escherichia coli (one strain), Citrobacter diversus (one strain), Klebsiella pneumoniae (two strains) or Serratia marcescens (two strains). Four hours after inoculation, treatment was begun with amikacin (15 mg/kg), mezlocillin (100 mg/kg), or ceftizoxime (50 mg/kg) alone or in two-drug combinations. Antibiotics were given intramuscularly every 6 h for 16 doses. Chambers were sampled for bacterial counts at the start of therapy, and 20, 44, and 92 h thereafter. Blood and chamber antibiotic levels were determined during the treatment course. In-vivo results were compared to in-vitro tests of inhibition, killing and synergism. Ceftizoxime alone was successful in vivo (greater than 6 log reduction in count) against the three strains of klebsiella and citrobacter, mezlocillin against one serratia strain, and amikacin alone against none of the strains. The best in-vitro correlation was with the minimum inhibitory concentration (MIC) at a high (10(8] inoculum for the beta-lactams and with the anaerobic MIC for amikacin. Among combinations, amikacin plus mezlocillin alone was successful against the three strains of klebsiella and serratia, but neither amikacin nor mezlocillin added to ceftizoxime were more successful than ceftizoxime alone. In-vitro chequerboard synergism was not predictive of in-vivo success. Mezlocillin alone was inactivated in vivo by all the strains except Ser. marcescens, and the E. coli strain inactivated both mezlocillin and ceftizoxime alone and in combination.

Agranulocytosis↗
PubMed2005

Functional recovery of peripheral blood mononuclear cells in modeled microgravity.

Immune function is suppressed in space flight, demonstrated by reduced mitogen-stimulated proliferation of postflight astronaut peripheral blood mononuclear cells (PBMCs). While flight studies are limited, the development of rotating wall vessel (RWV) bioreactors, such as the high aspect ratio vessel (HARV), has facilitated ground-based studies of the effects of modeled microgravity (MMG) on cell-mediated immunity. Astronauts regain immune function 3 days postflight, but this recovery has not yet been demonstrated following MMG. MMG eliminated phytohemagglutinin (PHA)-stimulated proliferation of PBMCs. Upon removal from HARV, full recovery was gradually achieved over a 72 h period, in agreement with postflight studies of astronauts. Recovery from MMG delayed, but did not reduce, the maximal proliferative response compared with PHA-activated stationary cultures. Likewise, peak expression of T cell surface activation markers CD69 and CD25 was delayed upon stimulation following exposure to MMG. MMG and recovery from MMG differentially affected the detection of IL-2 and IFN in supernatants. Further development of this model of immune recovery is important for investigating the mechanisms of immune suppression and recovery in space flight, as well as possible countermeasures to prevent immunosuppression or enhance recovery. Given the analogous immune suppression observed in microgravity, MMG, and aging, further investigation may also lead to advances in anti-aging medicine.

Adolescent↗
PubMed2001

Spectral statistics of instantaneous normal modes in liquids and random matrices.

We study the statistical properties of eigenvalues of the Hessian matrix H (matrix of second derivatives of the potential energy) for a classical atomic liquid, and compare these properties with predictions for random matrix models. The eigenvalue spectra (the instantaneous normal mode or INM spectra) are evaluated numerically for configurations generated by molecular dynamics simulations. We find that distribution of spacings between nearest-neighbor eigenvalues, s, obeys quite well the Wigner prediction s exp(-s(2)), with the agreement being better for higher densities at fixed temperature. The deviations display a correlation with the number of localized eigenstates (normal modes) in the liquid; there are fewer localized states at higher densities that we quantify by calculating the participation ratios of the normal modes. We confirm this observation by calculating the spacing distribution for parts of the INM spectra with high participation ratios, obtaining greater conformity with the Wigner form. We also calculate the spectral rigidity and find a substantial dependence on the density of the liquid.

Journal Article↗
PubMed2003

Slow dynamics of a confined supercooled binary mixture: direct space analysis.

Dynamical properties of a Lennard-Jones binary mixture embedded in an off-lattice matrix of soft spheres are studied in the direct space upon supercooling by molecular dynamics simulations. On lowering the temperature, the smaller particles tend to avoid the soft sphere interfaces and correspondingly their mobility decreases below one of the larger particles. The system displays a dynamic behavior, consistent with the mode coupling predictions. A decrease in the mode coupling crossover temperature with respect to the bulk is found. We however find that the range of validity of the theory shrinks with respect to the bulk. This is due to the change in the smaller particle mobility and to a substantial enhancement of hopping processes well above the crossover temperature upon confinement.

Journal Article↗
PubMed2003

Cellular automata model simulating complex spatiotemporal structure of wide jams.

According to the empirical observation of highway traffic, inside wide moving jams there is a complex spatiotemporal structure: jam is not compact and relatively large values of the time and the distance headway are visible. We present a cellular automata model by introducing "jam headway" and "jammed status" to simulate that complex structure. Using computer simulations, the fundamental diagram, the space-time plots, the time series of the density in the jams, and the 1-min average data of this model are analyzed. It is shown that compared to other existing models, this model can display the experimental characteristics of the wide moving jams.

Journal Article↗
PubMed2004

Filamentation of femtosecond light pulses in the air: turbulent cells versus long-range clusters.

The filamentation of ultrashort pulses in air is investigated theoretically and experimentally. From the theoretical point of view, beam propagation is shown to be driven by the interplay between random nucleation of small-scale cells and relaxation to long waveguides. After a transient stage along which they vary in location and in amplitude, filaments triggered by an isotropic noise are confined into distinct clusters, called "optical pillars," whose evolution can be approximated by an averaged-in-time two-dimensional (2D) model derived from the standard propagation equations for ultrashort pulses. Results from this model are compared with space- and time-resolved numerical simulations. From the experimental point of view, similar clusters of filaments emerge from the defects of initial beam profiles delivered by the Teramobile laser facility. Qualitative features in the evolution of the filament patterns are reproduced by the 2D reduced model.

Journal Article↗
PubMed2004

Negative group velocity and group delay in left-handed media.

The dynamics of wave propagation in media with negative index of refraction is analyzed through analytical calculations, simulations, and experiments. Using a free space setup, the transmission characteristics of two split ring resonator and strip wire left-handed media (LHM), designed for operation at K -band frequencies (18-26 GHz), are measured. The first LHM, which is 3 unit cells long in the propagation direction, exhibits a maximum negative group delay of -0.9 ns . The second LHM (4 unit cells long) exhibits a maximum negative group delay of -1.2 ns . For both LHM the bandwidth of the negative group delay (and hence the negative group velocity) region was approximately 250 MHz.

Journal Article↗
PubMed2001

Electrostatic mode excitation in electron holes due to wave bounce resonances.

A kinetic theory of resonant interaction between electrostatic waves and the bounce motion of electrostatically trapped electrons is developed. Precise criteria are derived for the stability of electrostatic potential structures which trap electrons in a highly magnetized plasma. The theory explains the energy transfer from electron phase space holes to waves observed in simulations. It may also account for the destabilization of electrostatic waves propagating obliquely to the geomagnetic field and some characteristics of the holes as observed in the auroral ionosphere.

Journal Article↗
PubMed1993

Effect of catecholamines on the ventricular myocyte action potential in raised extracellular potassium.

We describe the relationship between catecholamines and raised extracellular potassium ([K+]o) on action potential parameters and calcium currents in isolated ventricular myocytes of the guinea-pig and relate these findings to the problem of understanding how the heart is protected from exercise-induced hyperkalaemia ([K+]a up to 8.5 mM). Action potential duration (APD90), amplitude and upstroke velocity were recorded in stimulated (2Hz) guinea-pig ventricular myocytes using whole-cell patch electrode recordings (37 degrees C). Cells were superfused with normal K+ Tyrode and with raised K+ Tyrode in the presence of either noradrenaline, adrenaline or raised calcium. Inward calcium current was measured using voltage clamp. Raised K+ (8, 12, 16 mM K+ Tyrode) caused a significant (P < 0.01) depolarisation, shortened the APD90 and decreased the action potential amplitude and upstroke velocity. In raised K+ Tyrode addition of noradrenaline (0.08-0.1 microM) or adrenaline (0.1-0.2 microM) increased action potential amplitude (P < 0.01), APD90 (P < 0.01) and upstroke velocity (P < 0.01) (measured only in 16 mM K+ Tyrode). In 12 mM K+ Tyrode raised Ca2+ (5-6 mM) increased action potential amplitude (P < 0.05) and shortened APD90 (P < 0.05). Addition of NA (0.08-0.1 microM) increased the inward Ca2+ current. All effects were fully reversible. In raised [K+]o increases in catecholamines and [Ca2+]o cause changes in action potential parameters that would be expected to maintain propagation of the cardiac action potential in the whole heart. Thus, in the ventricular myocyte the increase in conductance to Ca2+ caused by catecholamines may be one factor that is important in minimising the potentially adverse effects of exercise-induced hyperkalaemia.

Action Potentials↗
PubMed2002

Microgravity studies of cells and tissues.

Controlled in vitro studies of cells and tissues under the conditions of microgravity (simulated on Earth, or actual in space) can improve our understanding of gravity sensing, transduction, and responses in living cells and tissues. This paper discusses the scientific results and practical implications of three NASA-related biotechnology projects: ground and space studies of microgravity tissue engineering (JSC-Houston), and the development of the cell culture unit for use aboard the International Space Station (ARC-Ames).

Animals↗
PubMed1998

Finite element formulation of biphasic poroviscoelastic model for articular cartilage.

The purpose of the present study was to develop a computationally efficient finite element model that could be useful for parametric analysis of the biphasic poroviscoelastic (BPVE) behavior of articular cartilage under various loading conditions. The articular cartilage was modeled as the BPVE mixture of a porous, linear viscoelastic, and incompressible solid and an inviscid and incompressible fluid. A finite element (FE) formulation of the BPVE model was developed using two different algorithms, the continuous and discrete spectrum relaxation functions for the viscoelasticity of the solid matrix. These algorithms were applied to the creep and stress relaxation responses to the confined compression of articular cartilage, and a comparison of their performances was made. It was found that the discrete spectrum algorithm significantly saved CPU time and memory, as compared to the continuous spectrum algorithm. The consistency analysis for the present FE formulation was performed in comparison with the IMSL, a commercially available numerical software package. It was found that the present FE formulation yielded consistent results in predicting model behavior, whereas the IMSL subroutine produced inconsistent results in the velocity field, and thereby in the strain calculation.

Algorithms↗
PubMed1998

The effect of fluid loss on the viscoelastic behavior of the lumbar intervertebral disc in compression.

A viscoelastic finite element model of a L2-L3 motion segment was constructed and used to study: (1) the behavior of the intervertebral disc with different amounts of nucleus fluid loss; and (2) the effect of different rates of fluid loss on the viscoelastic behavior of the disc. The results indicate that: (1) The viscoelastic behavior of the intervertebral disc depends to a large extent on the rate of fluid loss from the disc; the intrinsic properties of disc tissue play a role only at the early stage of compressive loading; (2) the axial strain increases, whereas the intradiscal pressure and the posterior radial disc bulge decrease with increasing fluid loss; (3) a decreasing fluid loss rate with a total fluid loss of 10 to 20 percent (from the nucleus) during the first hour of compressive loading best predicts the overall viscoelastic behavior of a disc.

Biomechanical Phenomena↗