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PubMed1994

Vector-averaged gravity does not alter acetylcholine receptor single channel properties.

To examine the physiological sensitivity of membrane receptors to altered gravity, we examined the single channel properties of the acetylcholine receptor (AChR), in co-cultures of Xenopus myocytes and neurons, to vector-averaged gravity in the clinostat. This experimental paradigm produces an environment in which, from the cell's perspective, the gravitational vector is "nulled" by continuous averaging. In that respect, the clinostat simulates one aspect of space microgravity where the gravity force is greatly reduced. After clinorotation, the AChR channel mean open-time and conductance were statistically not different from control values but showed a rotation-dependent trend that suggests a process of cellular adaptation to clinorotation. These findings therefore suggest that the ACHR channel function may not be affected in the microgravity of space despite changes in the receptor's cellular organization.

Acetylcholine↗

PubMed2005

A model of chromosome aberration induction: applications to space research.

A mechanistic model and Monte Carlo code simulating chromosome aberration induction in human lymphocytes is presented. The model is based on the assumption that aberrations arise from clustered DNA lesions and that only the free ends of clustered lesions created in neighboring chromosome territories or in the same territory can join and produce exchanges. The lesions are distributed in the cell nucleus according to the radiation track structure. Interphase chromosome territories are modeled as compact intranuclear regions with volumes proportional to the chromosome DNA contents. Both Giemsa staining and FISH painting can be simulated, and background aberrations can be taken into account. The good agreement with in vitro data provides validation of the model in terms of both the assumptions adopted and the simulation techniques. As an application in the field of space research, the model predictions were compared with aberration yields measured among crew members of long-term missions on board Mir and ISS, assuming an average radiation quality factor of 2.4. The agreement obtained also validated the model for in vivo exposure scenarios and suggested possible applications to the prediction of other relevant aberrations, typically translocations.

Chromosome Aberrations↗

PubMed1998

Hormonal changes during a 20-week confinement.

BACKGROUND: When the European Space Agency planned the EUROMIR'95 long-duration flight with a European astronaut on board the Russian orbital MIR station, it organized simultaneously a ground simulation, called the Human Behaviour Study, of this manned space mission. The ground simulation was a confinement experiment, and this paper describes the changes in volume-regulating hormones that occurred during and after 20 weeks of confinement. METHODS: In a normobaric diving chamber, 3 subjects were confined for 135 d. Arterial pressure, plasma concentrations of blood volume-regulating hormones (active renin and arginine-vasopressin), and urinary variables (aldosterone, arginine-vasopressin, and metabolites of catecholamines) were measured before, during, and after confinement. RESULTS: Arterial pressure was increased from week 1 until week 15 of confinement, while heart rate was elevated from week 6 until the end of the simulation. Plasma active renin was elevated throughout the confinement (after week 6). Urine volume increased transitively on the first 2 d of confinement. CONCLUSIONS: The results obtained during this long-term confinement experiment have major importance regarding concerns about spaceflight and bed rest data, because we observed hormonal changes during the experiment that normally are assigned to the fluid shift that occurs in weightlessness or in the head-down tilt position (i.e., an increase of renin, an increase of urinary volume during the first two days, and a decreased urinary cyclic guanosine monophosphate.

Aldosterone↗

PubMed1994

Reduced phase encoding in spectroscopic imaging.

The effect of different spatial-encoding (k-space) sampling distributions are evaluated for magnetic resonance spectroscopic imaging (MRSI) using Fourier reconstruction. Previously, most MRSI studies have used square or cubic k-space functions, symmetrically distributed. These studies examine the conventional k-space distribution with spherical distribution, and 1/2 k-space acquisition, using computer simulation studies of the MRSI acquisition for three spatial dimensions and experimental results. Results compare the spatial response function, Gibbs ringing effects, and signal contamination for different spatial-encoding distribution functions. Results indicate that spherical encoding, in comparison with cubic encoding, results in a modest improvement of the response function with approximately equivalent spatial resolution for the same acquisition time. For spin-echo acquired data, reduced acquisition times can readily be obtained using 1/2 k-space methods, with a concomitant reduction in signal to noise ratio.

Adenosine Triphosphate↗

PubMed2004

Development of softcore potential functions for overcoming steric barriers in molecular dynamics simulations.

In this work, we describe the development of softcore potential functions that permit occasional "tunneling" through the regions of conformational space during molecular dynamics (MD) simulations, which would otherwise be sterically prohibited. The modification consists of a truncation of the nonbonded interaction before the steeply repulsive region encountered at short interatomic distances. This modification affects both Lennard-Jones and Coulomb parts of the nonbonded potential. Critical to success is the choice of appropriate pairwise switching distances at which this modification should be made. In the present work, these are calculated based on potential of mean force functions extracted from model system molecular dynamics simulations. We believe that these functions describe the dynamic short-range interactions much better than mean force potentials derived from an ensemble of static structures (e.g. protein data bank (PDB)). Once a set of mean force potentials is obtained, a single empirical parameter, effective barrier height, is employed to determine switching distances for all pairwise atomic interactions. Changing this single parameter allows adjustment of the "softness" of the whole system. We tested the applicability of the new softcore potentials in a loop structure optimization study. The H1 loop in the antibody 17/9 was selected as our test case because substantial repacking of loop residues in the dense protein environment is necessary for successful relaxation of random initial conformations. Softcore simulations converted to correct loop conformations, in contrast to standard simulations which never sampled this structure even after 10 ns. The resulting root mean square deviation (RMSD) values (below 1.3 A for all heavy atoms of the loop) demonstrate the usefulness of the approach based on mean force derived softcore functions.

Amino Acids↗

PubMed2002

Changes in regional ventilation after autologous blood clot pulmonary embolism.

BACKGROUND: Previous studies have suggested that pulmonary embolism (PE) and pulmonary artery occlusion result in a shift in alveolar ventilation away from unperfused regions. This study aimed to directly assess changes in regional specific ventilation (sV(A)) due to autologous blood clot PE using positron emission tomography. METHODS: Pulmonary embolism was created in six anesthetized, paralyzed, and mechanically ventilated sheep by injecting cylindrical clots of autologous blood (7 mm in diameter and height). Clots were progressively infused into a central vein until a stable mean pulmonary artery pressure between 30 and 40 mmHg was achieved. A multislice positron emission tomography camera was used to image 15 contiguous, 6.5-mm-thick transverse cross-sections of the chest beginning just above the diaphragm. sV(A) from perfused regions (sV(A),(p)) was assessed as the ventilatory turnover rate of the tracer NN after central venous injection of NN-labeled saline. RESULTS: Pulmonary embolism obstructed flow to 64% of imaged areas. Before PE, (sV(A),(p))was equivalent in areas that would remain perfused and those that would become embolized after PE (0.021 +/- 0.007 0.021 +/- 0.006 s(-1); P = nonsignificant). After PE, sV(A),(p) of areas remaining perfused increased to 0.033 +/- 0.011 s (-1) (P < 0.005). This effect on regional sV(A),(p) could have been caused by active redistribution of sV(A),(p) or by a reduction in tracer concentration of perfused areas due to the dead space common to perfused and embolized regions. Model simulations indicated that the common dead-space effect could only explain a small part of the sV(A),(p) increase. CONCLUSIONS: An increase in sV(A),(p) of perfused regions occurs following PE with 7-mm autologous blood clots. This increase is most likely caused by a shift in ventilation away from embolized areas mediated by hypocapnic pneumoconstriction.

Algorithms↗

PubMed2001

RNase-stable RNA: conformational parameters of the nucleic acid backbone for binding to RNase T1.

An RNA sequence showing high stability with respect to digestion by ribonuclease T1 (RNase T1) was isolated by in vitro selection from an RNA library. Although ribonuclease T1 cleaves single-stranded RNA specifically after guanosine residues, secondary structure calculations predict several guanosines in single-stranded areas. Two of these guanosines are part of a GGCA-tetraloop, a recurring structure element in the secondary structure predictions. Molecular dynamics simulations of the conformation space of the nucleotides involved in this tetraloop show on the one hand that the nucleic acid backbone of the guanosines cannot realise the conformation required for cleavage by RNase T1. On the other hand, it could be shown that an RNA molecule not forced into a tetraloop occupies this conformation several times in the course of the simulation. The simulations confirm the GGCA-tetraloop as an RNase-stable secondary structure element. Our results show that, besides the known prerequisite of a single-stranded RNA, RNase T1 has additional demands on the substrate conformation.

Base Sequence↗

PubMed2005

Toward a new paradigm in hospital-based pediatric education: the development of an onsite simulator program.

OBJECTIVE: The low incidence of crises in pediatrics, coupled with logistic issues and restricted work hours for trainees, hinders opportunities for frequent practice of crisis management and teamwork skills. We hypothesized that a dedicated simulator suite contiguous to the intensive care unit (ICU) would enhance the frequency and breadth of critical-incident training for a range of clinicians. DESIGN: Descriptive study. SETTING: A tertiary-care pediatric teaching hospital. MEASUREMENTS AND MAIN RESULTS: A realistic pediatric simulator suite was constructed 100 feet from the ICU, at a total base cost of $290,000. The simulation room is an exact replica of an ICU bed space, incorporating high-fidelity mannequin simulators. To capture an even wider audience, a portable unit was also created. Leaders from seven departments-critical care, cardiac intensive care, emergency medicine, transport medicine, anesthesia, respiratory care, and general pediatrics-completed instructor training to ensure effective debriefing techniques. Pediatric staff, including 100% of critical care fellows, 86% of nurses, 90% of respiratory therapists, and 74% of pediatric house staff, participated in >1500 learning encounters per year. All individuals were trained during their normal workday in the hospital. Courses in crisis resource management, skills acquisition, annual review, orientation, and trauma management (1,116, 98, 90, 60, and 60 encounters per year, respectively) were all designed by a multidisciplinary committee to ensure goal-directed education to a range of audiences. Annual costs were on par with those at other centers (approximately 44 dollars per trainee encounter). CONCLUSIONS: An onsite and comprehensive simulation program can significantly increase the opportunities for clinicians from multiple disciplines, in the course of their daily routines, to repetitively practice responses to pediatric medical crises. After an initial capital investment, the training appears to be cost-effective. Hospital-based simulator suites may point the way forward as a new paradigm for the effective education of today's busy clinicians.

Clinical Competence↗

PubMed2004

Modeling extracellular space electrodiffusion during Leão's spreading depression.

Computational modeling of spreading depression (SD) has been used increasingly to study the different mechanisms that are involved in this phenomenon. One of them that is still under discussion involves the mechanisms that originate the extracellular electrical field responsible for the dc potential shift. The main goal of this paper is to present a mathematical derivation for the extracellular electric field that is incorporated in a SD model that has the basic structure of Tuckwell and Miura's model, but with the ionic variations calculated electrochemically. Electrodiffusion equations were used to describe the ionic movement of the four ions Na+, K+, Cl-, and Ca2+. These are mutually coupled by the electric field within the extracellular space (ECS). The results from the simulations show that the model is able to calculate the effect of the ionic changes along the ECS on the electric field, and to reproduce the SD in respect to the most important features that characterize the phenomenon experimentally in the retina or hippocampus. It is suggested that the extracellular negative field-potential shift during SD is due to an electrical field generated by a Goldman-Hodgkin-Katz equation acting within the ECS.

Action Potentials↗

PubMed2001

Assembly of a tetrameric alpha-helical bundle: computer simulations on an intermediate-resolution protein model.

Discontinuous molecular dynamics (DMD) simulation on an intermediate-resolution protein model is used to study the folding of an isolated, small model peptide to an amphipathic alpha-helix and the assembly of four of these model peptides into a four-helix bundle. A total of 129 simulations were performed on the isolated peptide, and 50 simulations were performed on the four-peptide system. Simulations efficiently sample conformational space allowing complete folding trajectories from random initial configurations to be observed within 15 min for the one-peptide system and within 15 h for the four-peptide system on a 500-MHz workstation. The native structures of both the alpha-helix and the four-helix bundle are consistent with experimental characterization studies and with results from previous simulations on these model peptides. In both the one- and four-peptide systems, the native state is achieved during simulations within an optimal temperature range, a phenomenon also observed experimentally. The ease with which our simulations yield reasonable estimates of folded structures demonstrates the power of the intermediate-resolution model developed for this work and the DMD algorithm and suggests that simulations of very long times and of multiprotein systems may be possible with this model.

Amino Acids↗

PubMed1979

EEG analysis gives model of neuronal template-matching mechanism for sensory search with olfactory bulb.

The spatial pattern of EEG activity at the surface of the olfactory bulb tends to be invariant with respect to input and to change to a new pattern whenever an animal is trained to expect or search for a particular odor. It is postulated here that the spatial EEG pattern is dependent on a neural template for that odor that is formed during training. This hypothesis is expressed in the form of a model consisting of an array of interconnected elements (1 X 10 or 6 X 6). Each element represents 2 excitatory and 2 inhibitory subsets of neurons with 3 types of internal feedback: negative, mutually excitatory, and mutually inhibitory. The elements are interconnected only by mutual excitation and mutual inhibition. Each neural subset is represented by a nonlinear differential equation; the connections are represented by modifiable coupling coefficients. With appropriate values of the time, coupling, and gain coefficients, and with input that is modelled on olfactory input, the set of 40 or 144 equations gives output that simulates the time and space patterns of the EEG. In the naive state the coefficients are uniform. A template is formed by giving input to selected elements, cross-correlating the outputs, and weighting the mutually excitatory coupling coefficient between each pair of elements by the corresponding correlation coefficient. When a template has been formed, input to nontemplate elements is treated as noise. Optionally a matched filter is made to simulate habituation by reducing the synaptic gain coefficients of those excitatory subsets that receive the noise. The model is tested by giving input to nontemplate elements and to none, part or all of the template elements. There are two outputs of the model. One is the spatial pattern Vj of the root mean square (rms) amplitudes of the individual outputs v(j, t) of the elements. The other output is the rms amplitude Erms of the ensemble average E(t) over v(j, t). The results show that Vj depends on the template and is relatively insensitive to input, whether or not input is given to template elements. However, Erms increases in proportion to the number of "hits" on the template. If the number of elements receiving noise does not exceed the number of elements in a template, or if the noise is matched with a habituation filter, then Erms rises above the noise level for a "hit" on any one or more template elements irrespective of location or combination. Vj conforms to the performance of the surface EEG. Erms is not yet accessible to physiological measurement.

Animals↗

PubMedDate not supplied

[The ultrasonic location of gas bubbles in the human bloodstream during work in a spacesuit].

The results of testing a procedure of ultrasonic location of the gas bubbles (GB) in man during space suit operations to simulate an extravehicular activity (EVA) are presented. Doppler echotachocardiograph "Rhythm" operating at ultrasonic frequency of 1.76 mHz was used as a GB detector. The device "Rhythm" integrated with a special flat transducer of 23 mm in diameter and 4 mm in width was positioned on the subject chest above the pulmonary artery projection. During 4-6 hour human operations while wearing pressurized (276-290 mm Hg) space suit, in 7 of 12 tests performed a stable and qualitative signal of the arterial blood flow in the lungs was recorded. In case of an unstable signal, in order that its quality be improved the posture of test subject was changed and the signal was recorded during a short-term expired breath-holding. Cardiac GB formation was noted during 6 tests in 2 subjects. The first GBs appeared at the 30th, 33rd, 70th, 111th, 114th and 180th minute after producing an operating reduced pressure in space suit. The time of GB detection on the average was 89.7 min. The maximum intensity of GB signal was 3-4 scores on Spencer's scale, but altitude decompression sickness symptoms did not develop in the test subjects. The risk of developing the altitude decompression sickness as opposed to the results of control experiments without use of space suit is discussed.

Adult↗

PubMedDate not supplied

Total body chlorine: calibration of the in vivo neutron activation measurement.

Total body chlorine (TBCI), used to estimate the extracellular space, is measured by delayed-gamma neutron activation (DGNA) using the reaction 37Cl(n, gamma)38Cl, at Brookhaven National Laboratory. During the calibration process, we noticed that different values were obtained when different amounts of Cl were placed in the phantom. This non-linear relationship is due to the thermal neutron flux suppression by the thermal neutron capture reaction 35Cl(n, gamma)36Cl. Monte Carlo simulations confirm the results of phantom measurements showing an inverse relationship between the Cl content in the phantom and the gamma-ray yield per gram Cl. Thus, it is important to calibrate the DGNA system for TBCl using phantom standards containing an amount of Cl close to that expected in the individual undergoing measurement.

Body Composition↗

PubMed1996

Analysis of impact of rigid projectiles on compound targets.

We developed a model to simulate a person, with and without protective armor, being subjected to an impact of a high speed, rigid projectile. The complex nature of the head and chest are simulated in our layered, spaced, various thickness targets made of different materials. A rigid projectile-target interaction model is described. Target resistance force was obtained from a generalized Poncelet equation. Good agreement between observed and computed penetration phenomena was obtained.

Computer Simulation↗

PubMed2001

Effect of simulated microgravity on human lymphocytes.

During space flight the function of the immune system changes significantly. Several papers reported that postflight the number and the proportion of circulating leukocytes in astronauts are modified (Leach, 1992), the in vitro mitogen induced T cell activation is depressed (Cogoli et al., 1985; Konstantinova et al. 1993) and there are detectable differences in cytokine production of leukocytes as well (Talas et al. 1983; Batkai et al. 1988; Chapes et al. 1992). One of the possible modifying forces is the microgravity condition itself. Our aim was to analyse mechanisms responsible for changing leukocyte functions in low gravity environment. For terrestrial simulation of microgravity we used a Rotary Cell Culture System (RCCS) developed by NASA. We investigated the effect of simulated microgravity on separated human peripheral blood mononuclear cells (PBMCs). We detected the populations of different cells by antibodies conjugated to fluorofors using a Flow Cytometer. Since space flight reduces the number of peripheral blood lymphocytes (Stowe et al., 1999) we supposed that apoptotic (programmed cell death) processes might be involved. This hypothesis was supported by the result of our earlier experiment demonstrating that simulated microgravity increased the level of secreted Tumor Necrosis Factor-alpha (TNFalpha, a known apoptotic signal molecule) significantly (Batkai et al. 1999).

Apoptosis↗

PubMed1996

Operational evaluation of the EXEMSI project. Experimental Campaign for the European Manned Space Infrastructure.

In general the EXEMSI project has proved to be very successful mission. It has demonstrated that it is indeed possible to perform a major and useful project in a short time and on a moderate budget. In addition to achieving the scientific objectives, this simulation project provided valuable experience in the training of members of chamber crew and ground control crew for their tasks. It covered all aspects of a mission from call for experiment proposals, crew selection and training, integration and testing of the facility and its equipment, to daily monitoring and managing of the mission, and finally post-isolation data collection and evaluation. These other activities were accomplished by a small team of experts in the astoundingly short time of 8 months. What was lacking in manpower, time and funds, was more than made up for by enthusiasm, expertise, team spirit, hard work and long hours well beyond the call of duty of all those involved. In addition to the specific and technological objectives reached, many lessons learned in this operation have been identified, which could help to improve future missions. The experience has shown pitfalls to be avoided in future mission, as well as points where some small increase in effort can make a considerable difference. With the prospect of long-term manned spaceflights looming in the near future and the ever increasing costs of such endeavors, the possibilities offered by running simulated missions on the ground should be seriously considered. Such simulations permit the study of scientific and operational aspects of a space mission prior to its actual implementation. A ground based simulation of an extended space mission may be run at a fraction of the cost of an in-orbit precursor mission of even one-week duration. However, careful planning of the simulation mission is required so that it may yield relevant information and useful experience. Lessons learned from the EXEMSI project should be taken into account in such planning. At the start clear goals should be formulated, that can provide clear guidelines for building up the infrastructure and defining the operational scenario. A long duration mission simulating the conditions on the Russian space station MIR could provide a valuable source of information and experience in preparing for the MIR '95 Mission.

Astronauts↗

PubMed2006

How the increase of the cervical disc space height affects the facet joint: an anatomy study.

STUDY DESIGN: In vitro study on the effect of increasing the height of the cervical disc space on the facet joint. OBJECTIVES: To demonstrate how facet joint articulation is affected by increasing the cervical disc space height. SUMMARY OF BACKGROUND DATA: A surgeon attempts to increase the disc space and inserts a larger artificial disc than normal in order to keep the intervertebral foramen open and the prosthesis stable. However, it is hypothesized by the current authors that this procedure could have an adverse effect on the facet joints. METHODS: Computerized tomography images passing through the disc space and the center of the C4-C7 facet joints (sagittal plane) were obtained from 15 cadaveric cervical spine specimens. A 1-mm incremental increase to a total 5 mm in disc space height was performed to simulate the changes seen in disc replacement. The change in the facet joint articulation overlap and space in the sagittal plane at normal and each displacement was measured. RESULTS: Each 1-mm incremental increase in disc space at C4-C5 translated to a decrease in the facet joint articulation overlap in the sagittal plane by approximately 8%. The mean facet joint space increased approximately 0.8 mm. At the C5-C6 and the C6-C7 levels, the articulation overlap decreased by approximately 7% and the facet joint space increased approximately 0.8 mm. CONCLUSIONS: There is a significant decrease of the facet joint articulation overlap in the sagittal plane and an increase in the facet joint space following an increase in the cervical disc space. The inappropriate increase of the disc space height may result in facet joint subluxation and could lead to the accelerated failure of the artificial disc.

Cadaver↗

PubMed1989

Altered sensory-motor control of the head as an etiological factor in space-motion sickness.

Mechanical unloading during head movements in weightlessness may be an etiological factor in space-motion sickness. We simulated altered head loading on Earth without affecting vestibular stimulation by having subjects wear a weighted helmet. Eight subjects were exposed to constant velocity rotation about a vertical axis with direction reversals every 60 sec. for eight reversals with the head loaded and eight with the head unloaded. The severity of motion sickness elicited was significantly higher when the head was loaded. This suggests that altered sensory-motor control of the head is also an etiological factor in space-motion sickness.

Head↗