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Advances in sensitivity encoding with arbitrary k-space trajectories.

New, efficient reconstruction procedures are proposed for sensitivity encoding (SENSE) with arbitrary k-space trajectories. The presented methods combine gridding principles with so-called conjugate-gradient iteration. In this fashion, the bulk of the work of reconstruction can be performed by fast Fourier transform (FFT), reducing the complexity of data processing to the same order of magnitude as in conventional gridding reconstruction. Using the proposed method, SENSE becomes practical with nonstandard k-space trajectories, enabling considerable scan time reduction with respect to mere gradient encoding. This is illustrated by imaging simulations with spiral, radial, and random k-space patterns. Simulations were also used for investigating the convergence behavior of the proposed algorithm and its dependence on the factor by which gradient encoding is reduced. The in vivo feasibility of non-Cartesian SENSE imaging with iterative reconstruction is demonstrated by examples of brain and cardiac imaging using spiral trajectories. In brain imaging with six receiver coils, the number of spiral interleaves was reduced by factors ranging from 2 to 6. In cardiac real-time imaging with four coils, spiral SENSE permitted reducing the scan time per image from 112 ms to 56 ms, thus doubling the frame-rate.

Brain↗

A model for the teaching of clinical techniques in root canal treatment.

A practical model to aid the understanding and practice of endodontic techniques is described. The model uses extracted teeth mounted in light-cured acrylic resin and set in a preformed model tray. Before mounting, the root surfaces of teeth are dipped in wax to simulate the periodontal ligament space. This model allows endodontic techniques to be practised in the operative technique classroom in a way that simulates the clinical situation and enables radiographs of good diagnostic quality to be taken during treatment. Subsequently, teeth can be reset to allow restoration of the root-filled tooth.

Audiovisual Aids↗

Physiological properties of rat hind limb muscles after 15 days of simulated weightless environment.

Weightlessness during space mission results in atrophic changes in those muscles which have maximum weight bearing function and consist primarily of slow twitch fibres. In the present study an animal model was designed to evaluate the effects of 15 days of hindlimb unloading (HU) in rats by tail suspension on the (i) weight of gastrocnemius (G), plantaris (P), both predominantly having fast twitch fibres and soleus (S) muscle, predominantly having fast twitch fibres and (ii) contractile properties viz peak twitch contraction (Pt) and peak tetanic contraction (Po) of GPS muscle. HU rats showed significant weight reductions of G (-17.9%), P (-13.3%) and S (-41.2%) muscles. Pt and Po were also reduced in HU group but when these were expressed per gm of GPS muscle, no significant changes in Pt and Po were observed. These findings confirm that HU in rats result in maximum atrophic change in those muscles which have predominantly slow twitch fibres and reductions in contractile properties of muscles are in proportion to reduction in muscle weight. Also, HU by tail suspension provides a good ground based model for developing the deconditioning of muscles as applicable to weightlessness of space and offers a scope for the development of various countermeasures.

Animals↗

Changes of catecholamine excretion during long-duration confinement.

Simulation studies have become the main source of data about small group interactions during prolonged isolation, from which it should be possible to anticipate crew problems during actual space missions. International Space Station (ISS) astronauts and cosmonauts will form one international crew, although living in different national modules. They will have joint flight protocols, and at the same time, fulfill a number of different tasks in accord with their national flight programs. Consistent with these concepts, we studied two simultaneously functioning groups in a simulation of ISS flight. The objective of this study was to investigate physiological parameters (such as catecholamine excretions) related to long-duration confinement in the hermetic chamber, simulating International Space Station flight conditions. We also planned to evaluate the relationship between epinephrine/norepinephrine with group dynamics and social events to predict unfavorable changes in health and work capability of the subjects related to psychological interaction in the isolation chamber.

Adaptation, Psychological↗

[The Jupiter-2 slow-rotation system].

The experience of space missions shows that functional disorders in crewmembers on the type of space motion sickness (SMS) may develop on the initial stage of flight. Longer exposure in micro-g causes a wide range of debilitative changes in the vital body systems. Artificial gravity produced by spacecraft rotation might be a universal tool to counteract the impacts of prolonged microgravity on the human body. However, the significance of SMS does not become less high because of a new factor, i.e. the rotating environment. Research system Jupiter 2 is a stand-alone slow-rotating ground facility for simulating motion sickness equivalent to its space form. The merits of this facility are the possibilities to control the intensity of exposure, perform long-term investigations of two active subjects simultaneously, and study the stages of body adaptation to this agent, and assess physical and operator's performance. The facility carries large expectations to occupational selection.

Equipment Design↗

MR imaging of hindbrain deformity in Chiari II patients with and without symptoms of brainstem compression.

We examined the MR appearance of the hindbrain deformity, including the upper cervical spinal canal and craniovertebral junction, in 33 patients with Chiari II malformation. In this disorder, there is impaction at birth of the medulla and cerebellar vermis into the upper cervical spine, resulting in obliteration of the subarachnoid space and scalloping of the dens. Spinal canal enlargement during the child's growth, combined with dorsal displacement of neural tissue, eventually causes marked widening of the precervical subarachnoid space. This enlargement may simulate an intradural mass. Our series documents the changes seen at birth and the progression of the widened precervical space through the first and second decades. Twelve (36%) of the 33 patients studied were symptomatic, with brainstem or longtract symptomatology, and 11 of these required surgery. This group was compared with the remaining 21 asymptomatic Chiari II patients to identify MR features associated with clinical deterioration. The level of descent of the hindbrain hernia was critical; eight of 12 symptomatic patients had a cervicomedullary kink at C4 or lower, while no asymptomatic patients had a fourth ventricle, medulla, or kink below C3-C4. The precervical cord subarachnoid space was slightly wider in asymptomatic patients, although there was great overlap. In five patients with follow-up scans, this space was seen to increase in width after laminectomy. A CSF flow void was present in the precervical space in about 25% of patients in both groups. In nine of 12 symptomatic patients, C1 arch indentation of the dura (causing significant compression) was confirmed surgically. However, seven (33%) of the 21 asymptomatic patients also had this appearance. Absolute measurement of the anteroposterior diameter of the canal at C1 ranged from 11 to 25 mm in both groups. Retrocollis, which persisted despite sedation for MR, was seen in two patients, both symptomatic. Recognition of the vermis, medullary kink, cervical cord, C1 arch, fourth ventricle, and precervical space in Chiari II patients is fundamental to the analysis of symptoms in

Adolescent↗

Molecular modeling and dynamics of biologically active peptides: application to neuropeptide Y.

A methodology is presented to allow results from molecular dynamics simulations to be combined with pharmacological binding and activity measurements in order to study the structure-function relationships of neuropeptide Y. This approach is a general one and should also be applicable to other peptides for which stable structures are known to exist in solution. The basis of the method is the calculation of energetically stable structures via a simulate and test approach. This approach uses molecular dynamics simulations to search conformational space in order to find low potential energy structures. The energetic stability of the structures is then tested via additional simulations. Once energetic stability has been achieved, perturbations of the structure may be performed via molecular modeling. The simulate and test approach is then used to obtain energetically stable structures for the perturbed compound. Comparison between the energetically stable starting and perturbed structures can then be made concerning both structural and dynamic changes. By using an energetically stable structure prior to the perturbation, the assumption can be made that the calculated differences are primarily due to the perturbation rather than to one or both of the structures reaching a more energetically favorable state. It should be emphasized that the calculations are being performed employing a limited physical model such that the influence of that model on the observed results must always be taken into account.

Amino Acid Sequence↗

A Monte Carlo multiple source model applied to radiosurgery narrow photon beams.

Monte Carlo (MC) methods are nowadays often used in the field of radiotherapy. Through successive steps, radiation fields are simulated, producing source Phase Space Data (PSD) that enable a dose calculation with good accuracy. Narrow photon beams used in radiosurgery can also be simulated by MC codes. However, the poor efficiency in simulating these narrow photon beams produces PSD whose quality prevents calculating dose with the required accuracy. To overcome this difficulty, a multiple source model was developed that enhances the quality of the reconstructed PSD, reducing also the time and storage capacities. This multiple source model was based on the full MC simulation, performed with the MC code MCNP4C, of the Siemens Mevatron KD2 (6 MV mode) linear accelerator head and additional collimators. The full simulation allowed the characterization of the particles coming from the accelerator head and from the additional collimators that shape the narrow photon beams used in radiosurgery treatments. Eight relevant photon virtual sources were identified from the full characterization analysis. Spatial and energy distributions were stored in histograms for the virtual sources representing the accelerator head components and the additional collimators. The photon directions were calculated for virtual sources representing the accelerator head components whereas, for the virtual sources representing the additional collimators, they were recorded into histograms. All these histograms were included in the MC code, DPM code and using a sampling procedure that reconstructed the PSDs, dose distributions were calculated in a water phantom divided in 20000 voxels of 1 x 1 x 5 mm3. The model accurately calculates dose distributions in the water phantom for all the additional collimators; for depth dose curves, associated errors at 2sigma were lower than 2.5% until a depth of 202.5 mm for all the additional collimators and for profiles at various depths, deviations between measured and calculated values were less than 2.5% or 1 mm.

Algorithms↗

A tree-based algorithm for determining the effects of solvation on the structure of salivary gland tripeptide NH3+-D-PHE-D-GLU-GLY-COO-.

A D-enantiomeric analog of the submandibular gland rat-1 tripeptide FEG (Seq: NH(3)(+)-Phe-Glu-Gly-COO(-)) called feG (Seq: NH(3)(+)-D-Phe-D-Glu-Gly-COO(-)) was examined by molecular dynamics simulations in water. Previous in vacuo simulations suggested a conformation consisting predominantly of interactions between the Phe side chain and glutamyl-carboxyl group and a carboxyl/amino termini interaction. The solvated peptide was simulated using two approaches which were compared-a single 400-ns simulation and a "simulation tree." The "tree" approach utilized 45 10-ns simulations with different conformations used as initial structures for given trajectories. We demonstrate that multiple short duration simulations are able to describe the same conformational space as that described by longer simulations. Furthermore, previously described in vacuo interactions were confirmed with amendments: the previously described head-to-tail arrangement of the amino and carboxyl termini, was not observed; the interaction between the glutamyl carboxyl and Phe side chain describes only one of a continuum of conformations present wherein the aromatic residue remains in close proximity to the glutamyl carbonyl group, and also interacts with either of the two available carboxyl groups. Finally, utilizing only two separate 10-ns trajectories, we were able to better describe the conformational space than a single 60-ns trajectory, realizing a threefold decrease in the computational complexity of the problem.

Algorithms↗

Effects of clinostat-microgravity on bone and calcium metabolism in rats.

Decreases in bone minerals and tissue volume after space flight have been observed in humans and animals, with a variety of results. Such data obtained from space flight experiments have given unsatisfactory results due to short periods of space flight and differences in age, body weights, and strain of animals used. Therefore, ground-based animal models have been developed in order to elucidate changes in bone affected by space flight. For example, a tail-suspended rat model has been established to study the effects of microgravity on bones by producing hind limb unloading. However, problems with this model due to the remaining forelimb loading and the unusual changes in blood current require the development of a new model simulating the physiological conditions of space flight. So we developed a three-dimension clinostat as an apparatus to produce a simulated microgravity similar to space flight by rotating rats equally in all directions. The purpose of the present study is to examine the effects of clinostat-microgravity on bone metabolism in rats.

Adrenal Glands↗

Body fluid metabolism at actual and simulated microgravity.

Recent observations from space missions indicate that weightlessness does not induce an increase in diuresis and natriuresis in astronauts. Rather, both oral fluid and sodium intake as well as renal fluid and sodium output appear reduced compared with the preflight condition. In addition, influences of reduced energy intake may be more important for total body fluid content inflight than generally assumed. Decreases in plasma volume and observations of upper body edema formation inflight indicate, in addition, an increased extravasation as a result of the headward fluid shift in weightlessness. Current simulations models of microgravity for body fluid metabolism are valid for simulations of the central fluid shift occurring in microgravity. Since weightlessness appears to decrease central venous pressure and does not induce an increased renal fluid and sodium excretion, while simulations models have opposite effects, additional models to simulate adaptation of body fluid metabolism to weightlessness might be necessary.

Adaptation, Physiological↗

Training astronauts using three-dimensional visualisations of the International Space Station.

Recent advances in personal computer technology have led to the development of relatively low-cost software to generate high-resolution three-dimensional images. The capability both to rotate and zoom in on these images superposed on appropriate background images enables high-quality movies to be created. These developments have been used to produce realistic simulations of the International Space Station on CD-ROM. This product is described and its potentialities demonstrated. With successive launches, the ISS is gradually built up, and visualised over a rotating Earth against the star background. It is anticipated that this product's capability will be useful when training astronauts to carry out EVAs around the ISS. Simulations inside the ISS are also very realistic. These should prove invaluable when familiarising the ISS crew with their future workplace and home. Operating procedures can be taught and perfected. "What if" scenario models can be explored and this facility should be useful when training the crew to deal with emergency situations which might arise. This CD-ROM product will also be used to make the general public more aware of, and hence enthusiastic about, the International Space Station programme.

Astronauts↗

Molecular dynamics simulation provides a possible structure for substance P-like peptides in aqueous solution.

A hypothetical conformation of the undecapeptide Substance P in aqueous solution is generated by molecular dynamics simulation for 284 ps. The conformation takes explicit solvent interactions into account as well as entropic effects to the extent that phase space is sampled in simulation. The initial conformation is taken from energy minimization studies and modified. In spite of fluctuations through 180 degrees in some backbone dihedral angles, the peptide settles with all backbone dihedrals within +/- 60 degrees from the initial values. In 130 ps, the radius of gyration decreases from 6.2 A to 5.5 A, whereas only fluctuation (+/- .2 A) is observed during the last 150 ps. The root-mean-square deviation at optimal superposition for a pair of conformations from the last 150 ps is 0.6 A, based on backbone atoms. The final structure is close-knit, nearly globular, and stabilized by several long-lived hydrogen bonds. The simulation conformation agrees with the scarce experimental data including a large number of structure-activity relationships. Thus, the simulation conformation is a likely candidate for one of the several conformations, the existence of which has been deduced from nuclear magnetic resonance data. Simulation results and experimental modification studies suggest that Phe 8 and Leu 10 are involved in the primary binding of SP to its receptors.

Amino Acid Sequence↗

Simulating biochemical networks at the particle level and in time and space: Green's function reaction dynamics.

We present a technique, called Green's function reaction dynamics (GFRD), for particle-based simulations of reaction-diffusion systems. GFRD uses a maximum time step such that only single particles or pairs of particles have to be considered. For these particles, the Smoluchowski equations are solved analytically using Green's functions, which are used to set up an event-driven algorithm. We apply the technique to a model of gene expression. Under biologically relevant conditions, GFRD is up to 5 orders of magnitude faster than conventional particle-based schemes.

Algorithms↗

[Effects of microgravity on human cognitive function in space flight].

In researches of space flight, studies on the effects of microgravity on cognitive function were relatively few. This paper reviews recent progress on this topic. It was shown that under the condition of microgravity, spatial orientation, motion perception and early process of object recognition were impaired to a certain degree. Capability of muscle movement and coordination was lowered, while higher cognitive functions, such as logic reasoning task, the speed and accuracy of short-term memory retrieval were less affected by microgravity. But long-term memory tasks and performance in which attention processes were needed (e.g., tracking task, selective response task), were impaired during space flight or under simulated weightlessness condition.

Cognition↗

Vector-averaged gravity alters myocyte and neuron properties in cell culture.

To investigate whether changes in the gravitational field of developing neurons and myocytes affect cellular development, we rotated cultures of embryonic spinal neurons and myocytes in a horizontal clinostat. Rotation in the clinostat produces, from the cells' perspective, a "vector-free" gravity environment by continuous averaging of the vector. In this way, rotation in the clinostat simulates the microgravity of space where the gravity vector is substantially reduced. At rotation rates of 1-50 rpm, cellular and nuclear areas of myocytes were significantly enlarged and the number of presumptive nucleoli increased. In neurons, frequent and large swellings appeared along neuritic shafts. Some of these changes were reversible after cessation of rotation. Since our data are generally consistent with findings from other cell types subjected to spaceflight, we suggest that the vector-free gravity environment of the clinostat appears to simulate, at least in part, the microgravity of space. Our data further show that cellular processes are sensitive to altered gravity and suggest that cell development in the microgravity of space may be significantly altered.

Animals↗

Changes in flux pattern of the central carbohydrate metabolism during kernel development in maize.

Developing kernels of the inbred maize line W22 were grown in sterile culture and supplied with a mixture of [U-13C6]glucose and unlabeled glucose during three consecutive intervals (11-18, 18-25, or 25-32 days after pollination) within the linear phase of starch formation. At the end of each labeling period, glucose was prepared from starch and analyzed by 13C isotope ratio mass spectrometry and high-resolution (13)C NMR spectroscopy. The abundances of individual glucose isotopologs were calculated by computational deconvolution of the NMR data. [1,2-(13)C2]-, [5,6-(13)C2]-, [2,3-(13)C2]-, [4,5-(13)C2]-, [1,2,3-(13)C3]-, [4,5,6-(13)C3]-, [3,4,5,6-(13)C4]-, and [U-(13)C6]-isotopologs were detected as the major multiple-labeled glucose species, albeit at different normalized abundances in the three intervals. Relative flux contributions by five different pathways in the primary carbohydrate metabolism were determined by computational simulation of the isotopolog space of glucose. The relative fractions of some of these processes in the overall glucose cycling changed significantly during maize kernel development. The simulation showed that cycling via the non-oxidative pentose phosphate pathway was lowest during the middle interval of the experiment. The observed flux pattern could by explained by a low demand for amino acid precursors recruited from the pentose phosphate pathway during the middle interval of kernel development.

Carbohydrate Metabolism↗

Structure determination of adeno-associated virus 2: three complete virus particles per asymmetric unit.

The atomic structure of adeno-associated virus 2 (AAV-2) has been determined to 3.0 A resolution. AAV-2 crystallized in space group P1, with unit-cell parameters a = 249.7, b = 249.7, c = 644.8 A, alpha = 90.0, beta = 101.2, gamma = 120.0 degrees. The crystals contained three full virus particles in the asymmetric unit, allowing 180-fold non-crystallographic symmetry averaging. The particle orientations were determined using the self-rotation function and found to have similar but resolvably different orientations. Approximate alignment of icosahedral and interparticle threefold screw symmetry led to a native Patterson that was interpretable in terms of approximate particle positions. Accurate positions required a Patterson correlation search that was constrained to be consistent with non-crystallographic threefold projection symmetry evident in the diffraction intensities. Initial phases to 15.0 A resolution were calculated by molecular replacement using the known structure of a distantly related homolog (23% sequence identity). Real-space averaging was performed and phases were extended from 15.0 to 3.0 A. An atomic model was fitted and refined using a simulated-annealing real-space procedure.

Crystallization↗