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Ion regulatory function of the human kidney in prolonged space flights.

Ten cosmonauts, who performed 30-175-day space flights aboard Salyut-4 and Salyut-6, and over 60 test subjects who were exposed to bed rest of up to 182 days and immersion of up to 56 days, were examined. The renal excretion of potassium and calcium increased, reaching a maximum by the 4-6th weeks in prolonged space flights and simulation studies. During the load tests with potassium and calcium salt, excretion postflight was much higher than preflight. During potassium chloride load tests a positive correlation between the blood content of aldosterone and potassium excretion existed, whereas during calcium lactate load tests an increased calcium excretion was accompanied by a decrease in blood parathyroid hormone concentration. The most probable cause of the negative ion balance in weightlessness is the reduced capacity of tissues to retain electrolytes due to the decreased ion pool capacity. Different exercises have been shown to exert a beneficial effect on electrolyte metabolism.

Aldosterone↗

Comparative informativeness for linkage of multiple SNPs and single microsatellites.

Single nucleotide polymorphisms (SNPs), or biallelic markers, are popular in genetic linkage studies due to their abundance in the genome, stability, and ease of scoring. We determined the 'information ratio' (IR) of closely spaced SNPs in simulated nuclear families and affected sib pairs (ASPs). (The IR is the ratio of actual average maximum lod score to the maximum lod score attainable if the marker were fully informative.) The nuclear families included parental information, whereas the ASPs did not. We analyzed these SNPs in two ways: (1) using multipoint analysis, and (2) treating the SNPs as 'composite markers' (i.e., haplotypes, as assigned by GENEHUNTER). (3) We also calculated the IR of a single microsatellite marker with multiple alleles and compared with the IR from the SNPs. For each set of input conditions, we simulated 1000 nuclear families, of 2, 3, 4, or 5 children each, as well as 1000 ASPs. We generated SNP marker data for strings of k = 1, 2, 3, 5, 7, and 10 SNP loci, with no recombination (theta = 0) and no linkage disequilibrium among the SNPs. The MAF (minor allele frequency) was either 0.5 or 0.25, and allele frequencies were the same for all k loci in any analysis. We also generated marker data for one single-locus microsatellite marker, with m = 3, 4, 5, 6, 7, and 9 equally frequent alleles. In all simulations, the disease was fully penetrant dominant, and there was no recombination or linkage disequilibrium among markers or between marker and disease. When multipoint analysis was used, we found that 5-7 closely spaced SNPs were usually enough to yield an IR of approximately 100%, for nuclear families of any size. However, for the ASPs, even 7-10 SNPs yielded an IR of only 70-80%. A microsatellite with 9 equally frequent alleles yielded about the same IR (86-88%) as a string of 4-5 SNPs, in nuclear families. SNPs analyzed as 'composite markers' analyses performed worse, due to the inherent ambiguity of SNP haplotyping.

Alleles↗

Carbonaceous grain processing in space and in the laboratory.

Laboratory simulations of carbonaceous grain processing which occurs in space are fundamental to outline an evolutionary pathway for these particles. We consider the UV spectral changes induced in hydrogenated carbon grains by thermal annealing, UV irradiation and ion bombardment. The results give the opportunity to interpret observations in different space environments. In particular, modelling of the optical properties, based on a description of the electronic structure of carbons, indicates small hydrogenated amorphous carbon grains, with different degrees of UV irradiation, as the carrier of the ubiquitous UV interstellar extinction bump.

Carbon↗

GC-MS in space research: decoding complex isothermal chromatograms recovered from space missions.

An analytical procedure is described to study GC-MS isothermal chromatograms simulating those recovered from space missions: in fact GC plays a predominant role in space missions devoted to characterizing the chemical composition of extra-terrestrial atmospheres. SIM (selected ion monitoring) detection was used for monitoring selected chemical classes: a simplified chromatogram can be obtained giving information on the chemical composition of the complex mixture. Since only isothermal GC chromatograms are allowed by flight constraints, a time axis transformation is required to make them homogeneous: i.e., constant retention increments for CH2 additions in terms of a homologous series. The order in the linearized chromatogram can be simply singled out with a chemometric approach based on the study of the Autocovariance Function (ACVF) computed on the digitized chromatogram: the plot of the experimental autocorrelation function (EACF) shows well-shaped peaks if constant interdistances are repeated in different regions of the chromatogram. The method was applied to standard mixtures representative of planetary atmospheres--hydrocarbons, nitriles and oxygenated compounds with between 3 and 12 carbon atoms--analyzed in flight simulating conditions. The coupling of the selectivity of SIM detection with the interpretation power of the EACF procedure proves to be a powerful tool for interpreting data recovered from space missions: the chemical composition of the mixture can be identified by handling the raw SIM chromatograms.

Automation↗

Sweeps in Space: Leveraging Geographic Data to Identify Beneficial Alleles in Anopheles gambiae.

As organisms adapt to environmental changes, natural selection modifies the frequency of nonneutral alleles. For beneficial mutations, the outcome of this process may be a selective sweep, in which an allele rapidly increases in frequency and perhaps reaches fixation within a population. Selective sweeps have well-studied effects on patterns of local genetic variation in panmictic populations, but much less is known about the dynamics of sweeps in continuous space. In particular, because limited movement across a landscape leads to unique patterns of population structure, spatial dynamics may influence the trajectory of selected mutations. Here, we use forward-in-time, individual-based simulations in continuous space to study the impact of space on beneficial mutations as they sweep through a population. In particular, we show that selection changes the joint distribution of allele frequency and geographic range occupied by a focal allele and demonstrate that this signal can be used to identify selective sweeps. We then leverage this signal to identify in-progress selective sweeps within the malaria vector Anopheles gambiae, a species under strong selection pressure from vector control measures. By considering space, we identify multiple previously undescribed variants with potential phenotypic consequences, including mutations impacting known IR-associated genes and altering protein structure and properties. Our results demonstrate a novel signal for detecting selection in spatial population genetic data that may have implications for genomic surveillance and understanding geographic patterns of genetic variation.

Animals↗

Biomechanical rationale for using polyetheretherketone (PEEK) spacers for lumbar interbody fusion-A finite element study.

STUDY DESIGN: To determine the effect of cage/spacer stiffness on the stresses in the bone graft and cage subsidence. OBJECTIVE: To investigate the effect of cage stiffness on the biomechanics of the fused segment in the lumbar region using finite element analysis. SUMMARY OF BACKGROUND DATA: There are a wide variety of cage/spacer designs available for lumbar interbody fusion surgery. These range from circular, tapered, rectangular with and without curvature, and were initially manufactured using titanium alloy. Recent advances in the medical implant industry have resulted in using medical grade polyetheretherketone (PEEK). The biomechanical advantages of using different cage material in terms of stability, subsidence, and stresses in bone graft are not fully understood. METHODS: A previously validated 3-dimensional, nonlinear finite element model of an intact L3-L5 segment was modified to simulate posterior interbody fusion spacers made of PEEK ("E" = 3.6 GPa) and titanium ("E" = 110 GPa) at the L4/5 disc with posterior instrumentation. Bone graft ("E" = 12 GPa) packed between the spacers in the intervertebral space was also simulated. The posterior lumbar interbody fusion spacer with instrumentation and graft represent a simulation of the condition present immediately after surgery. RESULTS: The peak centroidal Von Mises stresses in the graft bone increased by at least 9-fold with PEEK spacers as compared to titanium spacer. The peak centroidal Von Mises stresses in the endplates increased by at least 2.4-fold with titanium spacers over the PEEK spacers. These stresses were concentrated at places where the spacer interfaced with the endplate. The stiffness of the spacer did not affect the relative motion (stability) across the instrumented (L4/5) segment. CONCLUSIONS: Spacers less stiff than the graft will: (1) provide stability similar to titanium cages in the presence of posterior instrumentation, (2) reduce the stresses in endplates adjacent to the spacers, and (3) increase the load transfer through the graft, as evident from the increase in stresses in graft.

Benzophenones↗

Sweeps in space: leveraging geographic data to identify beneficial alleles in Anopheles gambiae.

As organisms adapt to environmental changes, natural selection modifies the frequency of non-neutral alleles. For beneficial mutations, the outcome of this process may be a selective sweep, in which an allele rapidly increases in frequency and perhaps reaches fixation within a population. Selective sweeps have well-studied effects on patterns of local genetic variation in panmictic populations, but much less is known about the dynamics of sweeps in continuous space. In particular, because limited movement across a landscape leads to unique patterns of population structure, spatial dynamics may influence the trajectory of selected mutations. Here, we use forward-in-time, individual-based simulations in continuous space to study the impact of space on beneficial mutations as they sweep through a population. In particular, we show that selection changes the joint distribution of allele frequency and geographic range occupied by a focal allele and demonstrate that this signal can be used to identify selective sweeps. We then leverage this signal to identify in-progress selective sweeps within the malaria vector Anopheles gambiae , a species under strong selection pressure from vector control measures. By considering space, we identify multiple previously undescribed variants with potential phenotypic consequences, including mutations impacting known IR-associated genes and altering protein structure and properties. Our results demonstrate a novel signal for detecting selection in spatial population genetic data that may have implications for genomic surveillance and understanding geographic patterns of genetic variation.

Journal Article↗

The role of cross-cultural factors in long-duration international space missions: lessons from the SFINCSS-99 study.

UNLABELLED: The role of cross-cultural factors in long-duration international space missions was examined during an isolation study that simulated many of the conditions aboard the International Space Station. METHODS: Interactions involving two heterogeneous crews and one homogeneous crew staying in isolation from 110 to 240 days were studied. Data consisted of post-isolation interviews with crewmembers, ground support personnel and management, observational data, and public statements by crewmembers. Data was analyzed using the techniques of linguistic anthropology and ethnography. RESULTS: Sub-cultural (organizational and professional) differences played a larger role than national differences in causing misunderstandings in this study. Conversely, some misunderstandings and conflicts were escalated by participants falsely assuming cultural differences or similarities. Comparison between the two heterogeneous crews showed the importance of training, personality factors, and commander and language skills in preventing and alleviating cultural misunderstandings. CONCLUSION: The study revealed a number of ways that cultural differences, real as well as assumed, can play a role and interact with other, non-cultural, factors in causing and/or precipitating conflict situations. It is postulated that such difficulties can be avoided by selecting culturally adaptive crewmembers and by cross-cultural and language training. Also the crew composition and role of commander were found to be important in mitigating conflict situations.

Adaptation, Psychological↗

In vitro modeling of spinal anesthesia. A digital video image processing technique and its application to catheter characterization.

BACKGROUND: Maldistribution of intrathecal local anesthetic has recently been implicated as a contributor to neurotoxic injury. In vitro modeling can be used to understand the distribution of anesthetic agents within the subarachnoid space. We describe an in vitro modeling technique that uses digital video image processing and its application to catheter injection of local anesthetic. METHODS: A clear plastic model of the subarachnoid space, including a simulated spinal cord and cauda equina, was filled with lactated Ringer's solution. Phthalocyanine blue dye of known concentration was injected into the model through small-bore (28-G) and large-bore (18-G) catheters. Injections were performed at a variety of controlled rates and sacral catheter positions, and the propagation of dye throughout the model was recorded on videotape, digitized by computer, and converted to a two-dimensional image of dye concentration. A subset of data was compared with results obtained from spectrophotometric analysis. RESULTS: There was a strong correlation (r = 0.98) between data obtained with analysis by digital video image processing and those obtained spectrophotometrically. Catheter size, catheter angle, and injection rate significantly influenced the distribution and peak concentration of simulated anesthetic. No major differences in distribution or peak concentration were observed with the two types of 28-G catheters. CONCLUSIONS: The digital video image processing technique can be used to quantify anesthetic distribution rapidly within a model of the subarachnoid space without disturbing the distribution. The current results demonstrate a strong dependence of anesthetic distribution on catheter angle, catheter size, and injection rate. Comparisons between 28-G catheters suggest that the difference in reported incidence of cauda equina syndrome associated with different 28-G catheters cannot be explained on the basis of differences in anesthetic distribution.

Anesthesia, Spinal↗

Use of the Numerov method to improve the accuracy of the spatial discretisation in finite-difference electrochemical kinetic simulations.

The fourth order accuracy of the spatial discretisation of time-dependent reaction-diffusion equations, in finite-difference electrochemical kinetic simulations in one space dimension, might well be achieved by means of the three-point Numerov method, instead of the 5(6)-point discretisation of second spatial derivatives, recently suggested in the literature. This is proven theoretically, and tested in simulations of potential-step chronoamperometric and current-step chronopotentiometric transients for the Reinert-Berg system, which is a classical example of electrochemical reaction-diffusion equations. Although less generally applicable than the 5(6)-point spatial scheme, the Numerov discretisation is easier to use, because it does not lead to increased linear equation matrix bandwidth, but results in quasi-block-tridiagonal matrices, similar to those for the conventional, second order accurate, three-point spatial discretisation. The simulations reveal that the Numerov method brings an improvement of accuracy and efficiency that is comparable with the one offered by the 5(6)-point spatial scheme.

Journal Article↗

[Effect of long-term hypergravitation on the skeletal-muscular tissue in rats].

The space flight or simulated gravitational unloading lead to the muscle atrophy, slow-to-fast transformation of muscle fibers and myofibrillar damages both in humans and animals (1, 7, 13, 17). This process could be prevented by the exercise training during space flight (1), (partly) by periodic weight support during unloading (13). It has been demonstrated in these studies that there is some level of force production necessary for the maintenance of skeletal muscle properties. It is known that adaptation to the physical training frequently induces augmentation in cross-sectional area (CSA) of muscle fibers (MF), transformation of fibers, augmentation of mitochondrial volume density, and increase in absolute volume of myofibrillas. Numerous observations suggest importance of gravitational loading in regulating muscle mass. The centrifuging is believed to be useful for preventing muscle functional and structural losses under microgravity. But there are few studies designed to investigate effect of artificial gravity on the skeletal musculature (2, 7). Our objective was to investigate structural adaptation in slow-twitch soleus muscle (percentage of connective tissue and central nuclei, fiber size, myosin heavy chain isotope, myofibrillar proteins and mitochondria volume density) after 19 and 33 days of hypergravity.

Adaptation, Physiological↗

Stabilization effect of traffic flow in an extended car-following model based on an intelligent transportation system application.

An extended car following model is proposed by incorporating an intelligent transportation system in traffic. The stability condition of this model is obtained by using the linear stability theory. The results show that anticipating the behavior of more vehicles ahead leads to the stabilization of traffic systems. The modified Korteweg-de Vries equation (the mKdV equation, for short) near the critical point is derived by applying the reductive perturbation method. The traffic jam could be thus described by the kink-antikink soliton solution for the mKdV equation. From the simulation of space-time evolution of the vehicle headway, it is shown that the traffic jam is suppressed efficiently with taking into account the information about the motion of more vehicles in front, and the analytical result is consonant with the simulation one.

Journal Article↗

State of Brassica rapa photosynthetic membranes in microgravity.

The structural characteristics of the photosynthetic apparatus of Brassica rapa plants grown on board the space shuttle Columbia (STS-87) for 15 days were examined using the methods of transmission electron microscopy and statistic programme STAT. Maintaining of the same growth conditions for control plants was realized with great accuracy using the Orbiter Environmental simulator in Kennedy Space Center. A grana number per a medial section 1.8 times decreased in microgravity. Considerable changes were also revealed in the grana structure in microgravity in comparison with th ground control, namely: 1/a greater diversity in the thylakoid length with granae and 2/ lateral shifting of the thylakoids lateral shifting of the thylakoids relative one to another. The previous mentioned pheomenon was found for 64% of the invested granae. Shifting of the thylakoids in the granae in microgravity led to increasing of the grana thylakoid surface exposed to a stroma. In addition, the volume of stromal thylakoids increased. The peculiarities in the photosynthetic apparatus structure in microgravity are supposed to be an evidence of decreasing in the light harvesting complex amount of photosystem II (PSII).

NASA Discipline Plant Biology↗

An algorithm for protein engineering: simulations of recursive ensemble mutagenesis.

An algorithm for protein engineering, termed recursive ensemble mutagenesis, has been developed to produce diverse populations of phenotypically related mutants whose members differ in amino acid sequence. This method uses a feedback mechanism to control successive rounds of combinatorial cassette mutagenesis. Starting from partially randomized "wild-type" DNA sequences, a highly parallel search of sequence space for peptides fitting an experimenter's criteria is performed. Each iteration uses information gained from the previous rounds to search the space more efficiently. Simulations of the technique indicate that, under a variety of conditions, the algorithm can rapidly produce a diverse population of proteins fitting specific criteria. In the experimental analog, genetic selection or screening applied during recursive ensemble mutagenesis should force the evolution of an ensemble of mutants to a targeted cluster of related phenotypes.

Algorithms↗

Foil coverage of a crawl-space floor: measurements and modeling of radon entry.

The mitigative impact of covering the floor of a crawl space with a membrane has been studied under well-defined and controlled conditions. The measurements have been done with a homogeneous column of dry sand covered with a sheet of polyethylene foil. An air-filled volume on top of the column simulates a crawl space. The experiments mainly concern long-term measurements of the crawl-space radon concentration in combination with steady-state diffusive and combined advective and diffusive transport through the sand column and crawl space. The experimental data are analyzed with both simplified mass-balance models for radon entry into the crawl space and with a two-dimensional numerical model based on a finite-difference approach. In all experiments the influence of atmospheric pressure variations is clearly present. For most experiments the agreement between calculations, which make use of independently measured transport parameters for both sand and foil, and measurements is within 10%. However, the discrepancy is larger for experiments with continuous advective transport from the crawl space to the sand. With undamaged foil, the calculations overestimate the measurements by 20%. Reversely, with an opening in the center of the foil, the calculations underestimate the measurements by 20-40%. The results show that under controlled conditions radon transport from a foil-covered sand column into a crawl-space can be described within 40% on basis of separately measured parameters.

Atmospheric Pressure↗

Simulation of peptide folding with explicit water--a mean solvation method.

A new approach to efficiently calculate solvent effect in computer simulation of macromolecular systems has been developed. Explicit solvent molecules are included in the simulation to provide a mean solvation force for the solute conformational search. Simulations of an alanine dipeptide in aqueous solution showed that the new approach is significantly more efficient than conventional molecular dynamics method in conformational search, mainly because the mean solvation force reduced the solvent damping effect. This approach allows the solute and solvent to be simulated separately with different methods. For the macromolecule, the rigid fragment constraint dynamics method we developed previously allows large time-steps. For the solvent, a combination of a modified force-bias Monte Carlo method and a preferential sampling can efficiently sample the conformational space. A folding simulation of a 16-residue peptide in water showed high efficiency of the new approach.

Computer Simulation↗

Essential dynamics of proteins.

Analysis of extended molecular dynamics (MD) simulations of lysozyme in vacuo and in aqueous solution reveals that it is possible to separate the configurational space into two subspaces: (1) an "essential" subspace containing only a few degrees of freedom in which anharmonic motion occurs that comprises most of the positional fluctuations; and (2) the remaining space in which the motion has a narrow Gaussian distribution and which can be considered as "physically constrained." If overall translation and rotation are eliminated, the two spaces can be constructed by a simple linear transformation in Cartesian coordinate space, which remains valid over several hundred picoseconds. The transformation follows from the covariance matrix of the positional deviations. The essential degrees of freedom seem to describe motions which are relevant for the function of the protein, while the physically constrained subspace merely describes irrelevant local fluctuations. The near-constraint behavior of the latter subspace allows the separation of equations of motion and promises the possibility of investigating independently the essential space and performing dynamic simulations only in this reduced space.

Animals↗