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Stimulation of the semicircular canals via the rotary chair as a means to test pharmacologic countermeasures for space motion sickness.

OBJECTIVE: Space motion sickness is currently treated pharmacologically with the empiric use of the H1 antihistamine promethazine, but use of this intervention is limited by the side effect of significant sedation. This creates a dilemma, as full cognition is particularly important during the same conditions likely to exacerbate the symptoms of space motion sickness. Using overstimulation of the semicircular canals with a rotary chair as a paradigm for space motion sickness, we evaluated four medications, commonly used for the treatment of terrestrial motion sickness and vertigo, for their efficacy in alleviating the simulated symptoms of space motion sickness. STUDY DESIGN: Randomized, prospective, double-blind study. SETTING: Tertiary referral center. PATIENTS: Healthy male and female volunteers, 18 years of age or older, without history of neurologic or psychiatric disorders, and with no known allergies or any previous adverse reactions to the drugs used. INTERVENTIONS: Lorazepam 1 mg, meclizine 25 mg, promethazine 25 mg, scopolamine 0.4 mg, or placebo. MAIN OUTCOME MEASURE: The ability of each treatment to control the nausea and vomiting associated with our paradigm for space motion sickness was evaluated by measuring time of rotation pre- and posttreatment and time of symptom onset pre-and posttreatment. RESULTS: Only scopolamine effected a mean change in duration of rotation that reached statistical significance when compared with placebo (p <0.008), with a greater than 40% increase in rotation time. Results with promethazine were not statistically significant. CONCLUSION: Results showed a rank order of efficacy of scopolamine > promethazine > placebo > meclizine > lorazepam. Scopolamine significantly increased rotation time, but none of the treatments resulted in a significant delay to onset of symptoms.

Adolescent↗

CT of the extraperitoneal space: normal anatomy and fluid collections.

Knowledge of the appearance and location of the normal fascial structures surrounding the kidneys and the bladder is the key to proper CT analysis of extraperitoneal fluid collections. Recent studies have shown that the renal fascia and the perirenal space are more complex than previously recognized. An extracapsular renal hematoma, confined against the kidney by the posterior renorenal septum within the perirenal space, can entirely simulate a subcapsular hematoma. Pancreatitis fluid can dissect between the discrete layers that constitute the posterior renal fascia, allowing fluid in the anterior pararenal space to extend posterior to the kidney without directly involving the posterior pararenal space. The umbilicovesical fascia separates the small perivesical space from the potential large reservoir of the prevesical space in the extraperitoneal portion of the pelvis. Fluid in the prevesical space can communicate directly with the retroperitoneal spaces surrounding the kidney. In addition to compartmental localization, CT features of the fluid itself or the presence of ancillary findings such as aortic aneurysm, enlarged pancreas, renal mass, or hydronephrosis will frequently indicate the cause and the extent of most extraperitoneal fluid collections.

Contrast Media↗

Application of time series analysis on molecular dynamics simulations of proteins: a study of different conformational spaces by principal component analysis.

Time series analysis is applied on the collective coordinates obtained from principal component analysis of independent molecular dynamics simulations of alpha-amylase inhibitor tendamistat and immunity protein of colicin E7 based on the Calpha coordinates history. Even though the principal component directions obtained for each run are considerably different, the dynamics information obtained from these runs are surprisingly similar in terms of time series models and parameters. There are two main differences in the dynamics of the two proteins: the higher density of low frequencies and the larger step sizes for the interminima motions of colicin E7 than those of alpha-amylase inhibitor, which may be attributed to the higher number of residues of colicin E7 and/or the structural differences of the two proteins. The cumulative density function of the low frequencies in each run conforms to the expectations from the normal mode analysis. When different runs of alpha-amylase inhibitor are projected on the same set of eigenvectors, it is found that principal components obtained from a certain conformational region of a protein has a moderate explanation power in other conformational regions and the local minima are similar to a certain extent, while the height of the energy barriers in between the minima significantly change. As a final remark, time series analysis tools are further exploited in this study with the motive of explaining the equilibrium fluctuations of proteins.

Amino Acid Sequence↗

Formation of double layers and electron holes in a current-driven space plasma.

Kinetic 1D simulations reveal that a weak density depression in a current-carrying plasma can lead to the formation of a strong potential ramp (double layer). The ramp and plasma turbulence it creates share many features with recent particle and field measurements in the auroral ionosphere. An electron beam accelerated by the ramp produces a series of propagating electron phase-space holes via a spatial two-stream instability. Electron heating associated with the formation and merging of these holes is found to influence the subsequent evolution of the potential ramp.

Journal Article↗

Effects of space flight conditions on the function of the immune system and catecholamine production simulated in a rodent model of hindlimb unloading.

UNLABELLED: The rodent model of hindlimb unloading has been successfully used to simulate some of the effects of space flight conditions. Previous studies have indicated that mice exposed to hindlimb-unloading conditions have decreased resistance to infections compared to restrained and normally housed control mice. OBJECTIVE: The purpose of this study was to clarify the mechanisms involved in resistance to infection in this model by examining the effects of hindlimb unloading on the function of the immune system and its impact on the production of catecholamines. METHODS: Female Swiss Webster mice were hindlimb-unloaded during 48 h and the function of the immune system was assessed in spleen and peritoneal cells immediately after this period. In addition, the kinetics of catecholamine production was measured throughout the hindlimb-unloading period. RESULTS: The function of the immune system was significantly suppressed in the hindlimb-unloaded group compared to restrained and normally housed control mice. Levels of catecholamines were increased in the hindlimb-unloaded group and peaked at 12 h following the commencement of unloading. CONCLUSION: These results suggest that physiological responses of mice are altered early after hindlimb unloading and that catecholamines may play a critical role in the modulation of the immune system. These changes may affect the ability of mice to resist infections.

Animals↗

Explicit and implicit water simulations of a beta-hairpin peptide.

The conformational properties of a beta-hairpin peptide (YITNSDGTWT) were studied by using both explicit and implicit water simulations. The conformational space of the peptide was scanned by using a restricted hydrogen-bonding search method. The search method used generated the conformational space with enough diversity and good representation of beta-hairpin structures. By using a total surface area-based treatment of hydrophobic interactions, implicit water simulations failed to discriminate between experimental beta-hairpin structures from the rest of the conformers present in the authors' conformation library. However, with inclusion of vibrational free energy and accounting separately for polar and nonpolar surface areas, the nuclear magnetic resonance structure was ranked successfully as the most stable conformation. There is a loose correlation between the conformational energies by the continuum model and the conformational energies by explicit water simulation for conformers with similar structures. However, in terms of solvation energy, both approaches have a much better correlation. By using proper treatment of surface effect (partition of the surface area into polar and nonpolar areas) and including vibrational free-energy contribution, the continuum models should be reliable. Furthermore, the authors found that, for this peptide, beta-hairpin structures have large vibrational entropy that contributes decisively to the stability of folded beta-hairpin structures. Proteins 1999;37:73-87.

Computer Simulation↗

Concentration polarization of fluorescent dyes in rat descending colonic crypts: evidence of crypt fluid absorption.

1. Using confocal microscopy, the rate of fluid absorption into isolated perifused descending rat colonic crypt lumens is estimated from the concentration polarization and distribution of fluorescein sulphonate (FS) and fluorescein isothiocyanate-dextran (FITC-dextran; molecular weight, 10,000) within the crypt lumens and pericryptal fluid. 2. The probe dyes enter the crypt via the luminal opening, are concentrated in the lumen, then escape into the pericryptal space via the paracellular spaces spanning the crypt wall. 3. FITC-dextran is maximally accumulated at a luminal depth of 60 microns to 5 times the concentration at the crypt opening (p < 0.001) and penetrates 150-200 microns along the lumen. FS is maximally accumulated within crypt lumen close to the opening. At crypt luminal depths 10-60 microns from the opening FS is accumulated by a factor of 1.5-2.0 above that found in HgCl2-treated tissue (p < 0.001). 4. Dye enters the crypt lumen slowly from the basal side, but from this side does not accumulate above the bathing solution concentration. 5. HgCl2 (20 microM) or theophylline (10 mM) completely inhibit concentrative accumulation of FITC-dextran and FS within the crypts and pericryptal space (p < 0.001). 6. Computer simulation of the dye uptake indicates that the rate of water flow into the crypt luminal opening is 1 x 10(-3) cm s-1 which is equivalent to 15 microliters (cm mucosa)-2 h-1. Approximately 75% of the fluid entering the crypt is abosrbed across the proximal 50 microns of crypt wall as a consequence of the large osmotic pressure gradient between the pericryptal and crypt luminal solutions. A pericryptal diffusion barrier with lower permeability than that across the crypt wall is required to simulate dye accumulation in the pericryptal space. Differences between FITC-dextran and FS accumulation are explained by the lower diffusion coefficient within the crypt lumen, and lower crypt wall permeability of FITC-dextran.

Absorption↗

Application of the keyhole technique to T1rho relaxation mapping.

PURPOSE: To demonstrate the feasibility of using the keyhole technique to minimize error in a least squares regression estimation of T(1rho) from magnetic resonance (MR) image data. MATERIALS AND METHODS: The keyhole method of partial k-space acquisition was simulated using data from a virtual phantom and MR images of ex vivo bovine and in vivo human cartilage. T(1rho) maps were reconstructed from partial k-space (keyhole) image data using linear regression, and error was measured with relation to T(1rho) maps created from the full k-space images. An error model was created based on statistical theory and fitted to the error measurements. RESULTS: T(1rho) maps created from keyhole images of a human knee produced levels of error on the order of 1% while reducing standard image acquisition time approximately by half. The resultant errors were strongly correlated with expectations derived from statistical theory. CONCLUSION: The error model can be used to analytically optimize the keyhole method in order to minimize the overall error in the estimation of the relaxation parameter of interest. The keyhole method can be generalized to significantly expedite all forms of relaxation mapping.

Animals↗

Statistical evaporation of rotating clusters. III. Molecular clusters.

Unimolecular evaporation of weakly bound clusters made of rigid molecules is considered from the points of view of statistical theories and molecular dynamics simulations. We explicitly work out expressions for the kinetic energy released and product angular momentum distributions within the sphere+sphere and sphere+linear rigid body assumptions of phase space theory (PST). Various approximations are investigated, including the shape of the interaction potential between the two fragments and the anharmonicity of the vibrational density of states. The comparison between phase space theory and simulation for nitrogen and methane clusters shows a quantitative agreement, thereby suggesting that PST is accurate in predicting statistical observables in a wide range of systems under various physical conditions.

Journal Article↗

Nonhomogeneous resolution of images of natural scenes.

The aim of this research is to model and simulate the loss of visual resolution as a function of retinal eccentricity in the perception of natural scenes. The model of visual resolution is based on a space-variant low-pass filter, having a variable convolution kernel according to retinal eccentricity. The parameters of the model are computed from psychophysical measures of visual acuity as a function of retinal eccentricity. The implementation of the model allowed us to generate images of scenes with nonhomogeneous space-variant resolution, simulating the filtering executed by the eye. These scenes are used to test and optimise the model by means of experiments in static vision (through tachistoscopic presentations) and in dynamic vision where the resolution of the scene is computed, in real-time, as a function of the location of gaze.

Contrast Sensitivity↗

[Male fertility in space].

The effects of simulated microgravity on mammalian reproduction were studied using tail-suspended mice, during parabolic flight in a jet plane and in a horizontal clinostat device. In the tail-suspended mouse, which is a model of the shift of body fluid in a microgravity environment, atrophy of the testis and decrease of serum testosterone level were observed. The sperm motility decreased in the muG condition produced by the parabolic flight. There were no statistically significant differences in the efficiency of achieving normal fertilization in vitro, but there was a statistically significant decrease in the number of embryos reaching the morula and blastocyst stages after 96 hours in culture under clinostat rotation. These results suggest that the process of fertilization in vitro is not sensitive to the gravitational vector. However, the possibility exists that microgravity increases the disturbance of spermatogenesis and sperm motility or the frequency of early embryonic lethality. On the possibility of reproduction in space, there are some problems such as the cosmic radiation besides gravity. It is necessary to carry out further experiments in outer space.

Animals↗

Embolus to the right atrium simulating myxoma.

A space-occupying mass of the right atrium was found by two-dimensional echocardiography and angiography in a 68-year-old woman whose clinical diagnosis indicated multiple pulmonary emboli. Since right heart myxomas frequently cause pulmonary thromboembolism, the patient was initially diagnosed by noninvasive and invasive techniques as having a right atrial myxoma. Surgery, however, revealed the pathologic findings of large thrombi of the right atrium, femoral and iliac veins, and pulmonary arteries. This case vividly demonstrates that deep venous thrombosis may embolize and lodge in the right atrial cavity simulating a right atrial myxoma.

Aged↗

Sampling of prenatal and postnatal offspring from individual rat dams enhances animal use without compromising development.

To assess prenatal and postnatal developmental status in the offspring of a group of animals, it is typical to examine fetuses from some of the dams as well as infants born to the remaining dams. Statistical limitations often arise, particularly when the animals are rare or especially precious, because all offspring of the dam represent only a single statistical observation; littermates are not independent observations (biologically or statistically). We describe a study in which pregnant laboratory rats were laparotomized on day 7 of gestation (GD7) to ascertain the number and distribution of uterine implantation sites and were subjected to a simulated experience on a 10-day space shuttle flight. After the simulated landing on GD18, rats were unilaterally hysterectomized, thus providing a sample of fetuses from 10 independent uteruses, followed by successful vaginal delivery on GD22, yielding postnatal samples from 10 uteruses. A broad profile of maternal and offspring morphologic and physiologic measures indicated that these novel sampling procedures did not compromise maternal well-being and maintained normal offspring development and function. Measures included maternal organ weights and hormone concentrations, offspring body size, growth, organ weights, sexual differentiation, and catecholamine concentrations.

Adrenal Glands↗

[METAPRINT: a metabolic fingerprint].

METAPRINT, a metabolic fingerprint based on predicted metabolic pathways and corresponding potential metabolites, has been developed. Calculated drug-likeness parameters (logP and MW) have been added into METAPRINT to achieve metabolic discrimination among the members of a chemical library. The application of METAPRINT in the design of cassette dosing experiments is demonstrated on a library of alpha-1a antagonists. Cassette design was performed by maximizing the intracassette Euclidean distances between compounds in METAPRINT space, using Metropolis Monte Carlo simulated annealing. Calculated distances in METAPRINT space were in accordance with experimental data.

Adrenergic alpha-Antagonists↗

Solution conformations and thermodynamics of structured peptides: molecular dynamics simulation with an implicit solvation model.

Calculations of the ensemble of solution conformations and thermodynamics of an analogue of the C-terminal helix of ribonuclease A (RN24) and of a synthetic, beta-hairpin forming peptide (BH8) are presented. For efficient sampling of conformation space, molecular dynamics simulations with an implicit solvent potential and umbrella sampling of the potential energy are performed. Starting from the fully extended chains, the simulations yield several folding and unfolding transitions between disordered (coil) conformations of the peptides and the "native" state (RN24, helix; BH8, hairpin); the simulations also lead to the occurrence of "misfolded" conformations (RN24, hairpin; BH8, helix). In agreement with experiment, the calculations predict 58% helix for RN24 at 275 K and an antiparallel-beta content of 38% at 275 K for BH8; the calculated probabilities for the misfolded species are 2% or smaller at all temperatures considered (250-1100 K). Good agreement is also shown between the calculated 3JHNalpha spin-spin coupling constants of RN24 and BH8 at 275 K, and those obtained from NMR experiments at the same temperature. From the calculated probabilities of helix (h), beta-hairpin (b), and coil (c), the free energy differences between the structured substates are DeltaGch=Gc-Gh approximately 1 kcal/mol and DeltaGbh>/=1.8 kcal/mol for RN24, and DeltaGcb approximately 0.7 kcal/mol and DeltaGhb>/=2.7 kcal/mol for BH8. The free energy difference between "correctly" folded and misfolded secondary structures are of interest for understanding the alpha to beta transition that is thought to play a role in amyloid fibril formation.

Amino Acid Sequence↗

Procedures necessary for the prevention of planetary contamination.

Studies of microbial survival in simulated deep-space conditions have established that these conditions will not sterilize contaminated spacecraft. Likewise, data presented at this and previous meetings of COSPAR have shown that many terrestrial microbes, particularly anaerobic sporeformers, readily tolerate simulated Martian environments. Any spacecraft landing on Mars must have a low probability of harboring any terrestrial organisms, especially sporeformers, if the goals of exobiology are not to be compromised. Before the planning, production and monitoring of sterile spacecraft can be undertaken, the theory and principles of sterilization and their application to the special problem of spacecraft sterilization must be understood. The response of a given population of microorganisms to sterilizing agents is affected by several factors; these factors in turn regulate the kinetics of the killing process. The only processes that achieve both surface and interior sterilization are heat and radiation. Of these, dry heat is the agent of choice. If all parts of the spacecraft are assembled under the most rigorous conditions of cleanliness, the capsule can be brought to terminal sterilization containing a total of not more than 10(5) viable organisms. These can be killed by exposure to 135 degrees for 24 hours with a confidence of greater than 10(4). Spacecraft must be specifically designed to withstand such heat sterilization without reduction of reliability. The number of labile parts must be kept to a minimum, sterilized by methods other than heat, and inserted into the sterilized spacecraft by sterile techniques. The entire process must be under very tight control with tests and records of every detail. The sterilized spacecraft must be encapsulated and remain therein during final testing and launch until the capsule is opened in deep space. The design and production engineer must understand how all these procedures will affect the spacecraft, and the biologist must constantly monitor and educate the engineers on the scope and limitations of these various sterilizing procedures.

Colony Count, Microbial↗

Monte Carlo simulation of the Leksell Gamma Knife: I. Source modelling and calculations in homogeneous media.

The Monte Carlo code PENELOPE has been used to simulate photon flux from the Leksell Gamma Knife, a precision method for treating intracranial lesions. Radiation from a single 6OCo assembly traversing the collimator system was simulated, and phase space distributions at the output surface of the helmet for photons and electrons were calculated. The characteristics describing the emitted final beam were used to build a two-stage Monte Carlo simulation of irradiation of a target. A dose field inside a standard spherical polystyrene phantom, usually used for Gamma Knife dosimetry, has been computed and compared with experimental results, with calculations performed by other authors with the use of the EGS4 Monte Carlo code, and data provided by the treatment planning system Gamma Plan. Good agreement was found between these data and results of simulations in homogeneous media. Owing to this established accuracy, PENELOPE is suitable for simulating problems relevant to stereotactic radiosurgery.

Computer Simulation↗

The effect of motional averaging on the calculation of NMR-derived structural properties.

The effect of motional averaging when relating structural properties inferred from nuclear magnetic resonance (NMR) experiments to molecular dynamics simulations of peptides is considered. In particular, the effect of changing populations of conformations, the extent of sampling, and the sampling frequency on the estimation of nuclear Overhauser effect (NOE) inter-proton distances, vicinal (3)J-coupling constants, and chemical shifts are investigated. The analysis is based on 50-ns simulations of a beta-heptapeptide in methanol at 298 K, 340 K, 350 K, and 360 K. This peptide undergoes reversible folding and samples a significant proportion of the available conformational space during the simulations, with at 298 K being predominantly folded and at 360 K being predominantly unfolded. The work highlights the fact that when motional averaging is included, NMR data has only limited capacity to distinguish between a single fully folded peptide conformation and various mixtures of folded and unfolded conformations. Proteins 1999;36:542-555.

Computer Simulation↗