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Drainage pits in cohesionless materials: implications for surface of Phobos.

Viking orbiter images show grooves and chains of pits crossing the surface of Phobos, many of which converge toward the large crater Stickney or its antipode. Although it has been proposed that the pits and grooves are chains of secondary craters, their morphology and geometric relations suggest that they are the surface traces of fractures in the underlying solid body of Phobos. Several models have been proposed to explain the pits, of which the most plausible are gas venting and drainage of regolith into open fractures. the latter mechanism is best supported by the image data and is the mechanism studied in this investigation. Drainage pits and fissures are modeled experimentally by using two rigid substrate plates placed edge to edge and covered by uniform thicknesses of dry fragmental debris (simulated regolith). Fracture extension is simulated by drawing the plates apart, allowing drainage of regolith into the newly created void. A typical drainage experiment begins with a shallow depression on the surface of the regolith, above the open fissure. Increased drainage causes local drainage pits to form; continued drainage causes the pits to coalesce, forming a cuspate groove. The resulting experimental patterns of pits and grooves have pronounced similarities to those observed on Phobos. Characteristics such as lack of raised rims, linearity of grooves and chains of pits, uniform spacing of pits, and progression from discrete pits to cuspate grooves are the same in the experiments and on Phobos. In contrast, gas-venting pits occur in irregular chains and have raised rims. These experiments thus indicate that the Phobos grooves and pits formed as drainage structures. The pit spacing in an experiment is measured at the time that the maximum number of pits forms, prior to groove development. The average pit spacing is compared to the regolith thickness for each material. Regression line fits indicate that the average spacing of drainage pits in unconsolidated, noncohesive regolith is nearly equal to the thickness of regolith and appears to gbe independent of the angle of repose, within the resolution of our experiments. This provides a simple means of estimating regolith thickness where drainage pits are present. On Phobos, two locations differing by 90 degrees in longitude have average pit spacings that suggest regolith thicknesses of 290 and 300 m, suggesting that large areas of Phobos have a nearly uniform regolith thickness of approximately 300 m.

Extraterrestrial Environment↗

Selection and evolution of bacteriophages in cellstat.

Objectives of this work were as follows: 1. to establish a laboratory experimental system utilizable in a biophysical approach to molecular evolution; and 2. to provide real world parameters to theories of molecular evolution, especially to Eigen's theory of quasi-species. Secretion type bacteriophage fd of E. coli, closely related phages and artificial chimera phages of fd, and a virulent phage Q beta of E. coli were cultured continuously in a specially designed fermenter called a "cellstat". A phage is cultured in a flow of host bacterial cells. Due to its high dilution rate, the mutant cell could not be selected in the cellstat. It was therefore recognized that the cellstat is suitable for study of the selection and evolution process of a bacteriophage under well-defined environmental conditions without interference from host cell mutations. Population dynamics of bacteriophages of various types in the cellstat were studied theoretically by computer simulation and experimentally. A genetically invariable pure population of phage behaves like an open non-linear chemical reaction system. An invariable mixed population shows a selection process, while a variable population generates an evolution process. Kinetic constants describing the dynamics were determined by curve fitting between the theoretical and the experimental curve obtained from competition experiments and from biological relaxation experiments. One of the most important kinetic parameters thus obtained was the selection coefficient, and its dependence on the base sequence of phage DNA. We drew a local landscape of the selection coefficient near the fd sequence on the base sequence space. From this landscape we were able to confirm the importance of slightly deleterious mutants in molecular evolution. We also confirmed the possibility of developing an evolutionary molecular engineering using a cellstat as an evolution reactor and fd phage as a working replicon. Novelties of this work were as follows: 1. the first stable continuous culture of a bacteriophage was achieved with a cellstat; 2. a local landscape of selection coefficient near the fd sequence on the sequence space was the first experimental drawing of such a map; 3. a biological relaxation method was realized to measure kinetic constants of a biological kinetic process, or molecular evolution; and 4. a practical engineering process of evolutionary molecular engineering was proposed.

Bacteriophages↗

Late fractionated potentials and continuous electrical activity caused by electrode motion.

Late fractionated potentials, recorded during cardiac mapping to find the source of a ventricular arrhythmia, have been ascribed particular localizing value. Re-entry is assumed when these highly amplified and filtered recordings span diastole during tachycardia. The purpose of this study was to see if such potentials can occur artifactually. A saline soaked 7 X 2 X 3 cm sponge was sewn to the epicardium of the right ventricle in five non-infarcted, open-chest dogs. Two bipolar button electrodes, one with 1 mm and one with 1 cm interelectrode spacing, were attached to the outer surface of the sponge and a bipolar wire hook electrode was placed just under the outer surface of the sponge. Thus all three electrodes were 3 cm from the nearest myocardium yet still subjected to cardiac motion. The electrodes were recorded at gains of 4,000-40,000 and filtered to pass 50-300 hertz. One to three rapid deflections were recorded during the QRS from all electrodes. In seven of the the 15 electrode recordings, two or three additional deflections, 1100-200 microV in amplitude, occurred after the QRS. These late potentials were fractionated and recurred reproducibly from cycle to cycle. In two cases, these late fractionated potentials could be made to span diastole by rapid pacing to simulate tachycardia. Clamping the sponge to sliminate motion between the sponge and electrode caused this late activity to disappear. Thus, in highly amplified and filtered recordings, electrode motion can cause artifacts resembling late fractionated potentials and continuous electrode activity.

Animals↗

Structure and interactions of fully hydrated dioleoylphosphatidylcholine bilayers.

This study focuses on dioleoylphosphatidylcholine (DOPC) bilayers near full hydration. Volumetric data and high-resolution synchrotron x-ray data are used in a method that compares DOPC with well determined gel phase dipalmitoylphosphatidylcholine (DPPC). The key structural quantity obtained is fully hydrated area/lipid A0 = 72.2 +/- 1.1 A2 at 30 degrees C, from which other quantities such as thickness of the bilayer are obtained. Data for samples over osmotic pressures from 0 to 56 atmospheres give an estimate for the area compressibility of KA = 188 dyn/cm. Obtaining the continuous scattering transform and electron density profiles requires correction for liquid crystal fluctuations. Quantitation of these fluctuations opens an experimental window on the fluctuation pressure, the primary repulsive interaction near full hydration. The fluctuation pressure decays exponentially with water spacing, in agreement with analytical results for soft confinement. However, the ratio of decay length lambda(fl) = 5.8 A to hydration pressure decay length lambda = 2.2 A is significantly larger than the value of 2 predicted by analytical theory and close to the ratio obtained in recent simulations. We also obtain the traditional osmotic pressure versus water spacing data. Our analysis of these data shows that estimates of the Hamaker parameter H and the bending modulus Kc are strongly coupled.

1,2-Dipalmitoylphosphatidylcholine↗

Integrated operation of continuous chromatography and biotransformations for the generic high yield production of fine chemicals.

The rapid progress in biocatalysis in the identification and development of enzymes over the last decade has enormously enlarged the chemical reaction space that can be addressed not only in research applications, but also on industrial scale. This enables us to consider even those groups of reactions that are very promising from a synthetic point of view, but suffer from drawbacks on process level, such as an unfavourable position of the reaction equilibrium. Prominent examples stem from the aldolase-catalyzed enantioselective carbon-carbon bond forming reactions, reactions catalyzed by isomerising enzymes, and reactions that are kinetically controlled. On the other hand, continuous chromatography concepts such as the simulating moving bed technology have matured and are increasingly realized on industrial scale for the efficient separation of difficult compound mixtures - including enantiomers - with unprecedented efficiency. We propose that coupling of enzyme reactor and continuous chromatography is a very suitable and potentially generic process concept to address the thermodynamic limitations of a host of promising biotransformations. This way, it should be possible to establish novel in situ product recovery processes of unprecedented efficiency and selectivity that represent a feasible way to recruit novel biocatalysts to the industrial portfolio.

Biotechnology↗

Biomechanical modeling and optimal control of human posture.

The present work describes the biomechanical modeling of human postural mechanics in the saggital plane and the use of optimal control to generate open-loop raising-up movements from a squatting position. The biomechanical model comprises 10 equivalent musculotendon actuators, based on a 40 muscles model, and three links (shank, thigh and HAT-Head, Arms and Trunk). Optimal control solutions are achieved through algorithms based on the Consistent Approximations Theory (Schwartz and Polak, 1996), where the continuous non-linear dynamics is represented in a discrete space by means of a Runge-Kutta integration and the control signals in a spline-coefficient functional space. This leads to non-linear programming problems solved by a sequential quadratic programming (SQP) method. Due to the highly non-linear and unstable nature of the posture dynamics, numerical convergence is difficult, and specific strategies must be implemented in order to allow convergence. Results for control (muscular excitations) and angular trajectories are shown using two final simulation times, as well as specific control strategies are discussed.

Algorithms↗

Robotic mitral valve surgery.

A renaissance in cardiac surgery has begun. The early clinical experience with computer-enhanced telemanipulation systems outlines the limitations of this approach despite some procedural success. Technologic advancements, such as the use of nitinol U-clips (Coalescent Surgical Inc., Sunnyvale, CA) instead of sutures requiring manual knot tying, have been shown to decrease operative times significantly. It is expected that with further refinements and development of adjunct technologies, the technique of computer-enhanced endoscopic cardiac surgery will evolve and may prove to be beneficial for many patients. Robotic technology has provided benefits to cardiac surgery. With improved optics and instrumentation, incisions are smaller. The ergometric movements and simulated three-dimensional optics project hand-eye coordination for the surgeon. The placement of the wristlike articulations at the end of the instruments moves the pivoting action to the plane of the mitral annulus. This improves dexterity in tight spaces and allows for ambidextrous suture placement. Sutures can be placed more accurately because of tremor filtration and high-resolution video magnification. Furthermore, the robotic system may have potential as an educational tool. In the near future, surgical vision and training systems might be able to model most surgical procedures through immersive technology. Thus, a "flight simulator" concept emerges where surgeons may be able to practice and perform the operation without a patient. Already, effective curricula for training teams in robotic surgery exist. Nevertheless, certain constraints continue to limit the advancement to a totally endoscopic computer-enhanced mitral valve operation. The current size of the instruments, intrathoracic instrument collisions, and extrathoracic "elbow" conflicts still can limit dexterity. When smaller instruments are developed, these restraints may be resolved. Furthermore, a working port incision is still required for placement of an atrial retractor, as well as needle, tissue, and suture retrieval. With the development of specialized retractors and a delivery/retrieval port, a truly endoscopic approach will be consistently reproducible. New navigation systems and image guided surgery portend an improving future for robotic cardiac surgery. Recently, we have combined robotically guided microwave catheters for ablation of atrial fibrillation with robotic mitral valve repairs (Fig. 8). Thus, we are beginning to achieve the ideal operation, with a native valve repair and a return to normal sinus rhythm. Robotic cardiac surgery is an evolutionary process, and even the greatest skeptics must concede that progress has been made toward endoscopic cardiac valve operations. Surgical scientists must continue to critically evaluate this technology in this new era of cardiac surgery. Despite enthusiasm, caution cannot be overemphasized. Surgeons must be careful because indices of operative safety, speed of recovery, level of discomfort, procedural cost, and long-term operative quality have yet to be defined. Traditional valve operations still enjoy long-term success with ever-decreasing morbidity and mortality, and remain our measure for comparison. Surgeons must remember that we are seeking the most durable operation with the least human trauma and quickest return to normalcy, all done at the lowest cost with the least risks. Although we have moved more asymptotically to these goals, surgeons alone must map the path for the final ascent.

Cardiac Surgical Procedures↗

Edge detection in medical images using a genetic algorithm.

An algorithm is developed that detects well-localized, unfragmented, thin edges in medical images based on optimization of edge configurations using a genetic algorithm (GA). Several enhancements were added to improve the performance of the algorithm over a traditional GA. The edge map is split into connected subregions to reduce the solution space and simplify the problem. The edge-map is then optimized in parallel using incorporated genetic operators that perform transforms on edge structures. Adaptation is used to control operator probabilities based on their participation. The GA was compared to the simulated annealing (SA) approach using ideal and actual medical images from different modalities including magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound. Quantitative comparisons were provided based on the Pratt figure of merit and on the cost-function minimization. The detected edges were thin, continuous, and well localized. Most of the basic edge features were detected. Results for different medical image modalities are promising and encourage further investigation to improve the accuracy and experiment with different cost functions and genetic operators.

Algorithms↗

A novel vented microisolation container for caging animals: microenvironmental comfort in a closed-system filter cage.

We designed a closed-system cage with vent ports that would allow continuous airflow in the occupied cage to ensure adequate ventilation and gas exchange. In this system, the metabolic heat loads of mice generate upward thermal air currents. Heat exits via the exhaust port, and room air enters via the intake port, providing adequate ventilation. Simulations based on computational fluid dynamics (CFD) helped us to optimize the cage's design. CFD simulations and smoke visualizations with a feeder-trough assembly illustrated the one-pass air circulation pattern and the lack of air recirculation, turbulence, and dead air space in our system. We used hot-film anemometry and smoke-test methodologies to show that adequate ventilation was provided. In a room with still air (0 air changes per hour [ACH]), a cage fitted with double wire-cloth filters (40 mesh size) and occupied by five mice has at least 12 ACH, whereas the same cage occupied by one mouse has 6 ACH. After five mice had occupied the cage for a week, its average temperature was 0.58C, relative humidity was 34%, and ammonia concentration was 3 ppm higher than that of the room. Our novel vented microisolation cage provides adequate intracage ACH, isolates mice from environmental contaminants, and contains allergenic particles within the cage in an environment appropriate for the species.

Animals↗

Robust and self-tuning blood flow control during extracorporeal circulation in the presence of system parameter uncertainties.

Three different discrete controllers were designed and tuned to be used in conjunction with a rotary blood pump during cardiopulmonary heart-lung support. The controllers were designed to operate in both steady and pulsatile modes. The system and methods were tested in a circulatory haemodynamic simulator. To guarantee stable control of the non-linear circulatory system in the presence of patient parameter uncertainties, a proportional plus integral (PI) and an H infinity controller were robustly tuned, using a non-linear time-varying model. (H infinity refers to the Hardy space, the set of bounded functions, analytic in the right half plane. The H infinity controller is the solution to the H infinity norm optimisation problem.) A self-tuning general predictive controller (GPC), together with an adaptive Kalman filter (KF) estimator, was compared with the two robustly tuned controllers. The closed-loop blood flow control circuit was set up in simulation routines first. The blood flow controllers were validated in a circulatory hydrodynamic simulator (MOCK) combined with a rotary blood pump. Parameters of the system simulator were changed continuously, and the controllers were tested over a wide range of different operating points. Disturbances in the form of discontinuous additive parameter uncertainties were applied. The closed-loop systems remained robustly stable. The robustly tuned H infinity controller showed the best control performance, in contrast to the GPC controller, which was near instability in regions of strongly varying non-linear system gain. Compared with the H infinity controller, the PI controller showed slightly worse behaviour, but the closed-loop response was acceptable, even in regions of strongly varying non-linear system gain and during pulsatile perfusion. The rotary blood pump could provide stationary and pulsatile perfusion under control conditions. Controlled variables were hereby mean blood flow, pulsatility index and heart rate. All three controllers were developed for an arterial mean flow of 0-6 l min(-1) and a heart rate of up to 70 beats per minute. Pulsatile closed-loop perfusion could provide up to 30 mmHg pressure variation in the simulated ascending aorta at a mean flow of 3 l min(-1).

Aorta↗

Spatially extended sound equalization in rectangular rooms.

The results of a theoretical study on global sound equalization in rectangular rooms at low frequencies are presented. The zone where sound equalization can be obtained is a continuous three-dimensional region that occupies almost the complete volume of the room. It is proved that the equalization of broadband signals can be achieved by the simulation of a traveling plane wave using FIR filters. The optimal solution has been calculated following the traditional least-squares approximation, where a modeling delay has been applied to minimize reverberation. An advantage of the method is that the sound field can be estimated with sensors placed in the limits of the equalization zone. As a consequence, a free space for the listeners can be obtained.

Journal Article↗

A general population-genetic model for the production by population structure of spurious genotype-phenotype associations in discrete, admixed or spatially distributed populations.

In linkage disequilibrium mapping of genetic variants causally associated with phenotypes, spurious associations can potentially be generated by any of a variety of types of population structure. However, mathematical theory of the production of spurious associations has largely been restricted to population structure models that involve the sampling of individuals from a collection of discrete subpopulations. Here, we introduce a general model of spurious association in structured populations, appropriate whether the population structure involves discrete groups, admixture among such groups, or continuous variation across space. Under the assumptions of the model, we find that a single common principle--applicable to both the discrete and admixed settings as well as to spatial populations--gives a necessary and sufficient condition for the occurrence of spurious associations. Using a mathematical connection between the discrete and admixed cases, we show that in admixed populations, spurious associations are less severe than in corresponding mixtures of discrete subpopulations, especially when the variance of admixture across individuals is small. This observation, together with the results of simulations that examine the relative influences of various model parameters, has important implications for the design and analysis of genetic association studies in structured populations.

Computer Simulation↗

Small-solute and middle-molecule clearances during continuous flow peritoneal dialysis.

Previous theoretic and clinical studies have shown that continuous flow peritoneal dialysis (CFPD) provides a high dose of small-solute removal; however, the dose of middle-molecule removal with CFPD therapy has not been evaluated. We used a variable-volume, two-compartment model to calculate theoretical steady-state solute kinetic profiles during CFPD, continuous ambulatory peritoneal dialysis (CAPD), and hemodialysis using a high-flux dialyzer (HFHD), for an anuric 70-kg patient and two measures of dose: equivalent renal clearance (EKR) and standard Kt/V (stdKt/V). Dose measures during each therapy were calculated for five solutes: urea, creatinine, vitamin B12, inulin, and beta 2-microglobulin. Fluid (1 L daily) was assumed to accumulate in and to be removed from the extracellular space, and non renal clearance was assumed to be zero for all solutes except beta 2-microglobulin. Calculated doses for CFPD were higher than for CAPD or HFHD when assessed by either EKR or stdKt/V. Dose enhancements for CFPD were highest for small solutes, but were still considerable for middle molecules. We conclude that CFPD achieves higher doses than CAPD or HFHD for both small-solute and middle-molecule removal.

Anuria↗

The Life Sciences Programme of the European Space Agency, and opportunities for radiation biology experiments.

With the advent of Europe's commitment to contribute the European Space Agency (ESA) to the NASA Space Transportation System (STS) by means of the Spacelab programme, a new area for research opportunities on Life Sciences has been created for the European scientific community. Although considered as a young and new discipline, the goals of Life Sciences research in space had soon been defined by the ESA advising Life Sciences Working Group in the beginning of 1977. The programme proposals of the various subdisciplines concentrated on the advantageous use of the microgravity environment, to study in more depth the gravity relevance of biological systems. It included, however, also the use of other factors during space flight which cannot be reproduced or adequately simulated on the ground: cosmic radiation in its total spectrum, particularly HZE particles, solar and UV radiation, vacuum, and the combination of radiation and weightlessness, etc. On this basis, call for proposals in the various subdisciplines resulted in experiments also in the field of radiation biology which were flown on the Spacelab 1 mission and which were selected for later missions. In particular, ESA is providing the science community with mission opportunities on Spacelab, either European or International, with platforms to be launched by STS, and with so called multi-user facilities (e.g. Biorack). Typically, the experiments will be the responsibility of the scientists, the integration and mission phase the responsibility of ESA. Both mission definition and experiment selection rests with the ultimate decision of the responsible ESA Programme Board. A further description of missions envisioned, the Spacelab facility, platforms, multi-user facilities and areas of research applicable to radiobiology will be given. ESA's continuing interaction with the scientific community through the Life Sciences Working Group, and the advice on future programmes will be stressed as a vital factor contributing to a European Life Sciences Programme in Space.

Adaptation, Physiological↗

Theoretical reconstruction of myotonia and paralysis caused by incomplete inactivation of sodium channels.

Muscle fibers from individuals with hyperkalemic periodic paralysis generate repetitive trains of action potentials (myotonia) or large depolarizations and block of spike production (paralysis) when the extracellular K+ is elevated. These pathologic features are thought to arise from mutations of the sodium channel alpha subunit which cause a partial loss of inactivation (steady-state Popen approximately 0.02, compared to < 0.001 in normal channels). We present a model that provides a possible mechanism for how this small persistent sodium current leads to repetitive firing, why the integrity of the T-tubule system is required to produce myotonia, and why paralysis will occur when a slightly larger proportion of channels fails to inactivate. The model consists of a two-compartment system to simulate the surface and T-tubule membranes. When the steady-state sodium channel open probability exceeds 0.0075, trains of repetitive discharges occur in response to constant current injection. At the end of the current injection, the membrane potential may either return to the normal resting value, continue to discharge repetitive spikes, or settle to a new depolarized equilibrium potential. This after-response depends on both the proportion of noninactivating sodium channels and the magnitude of the activity-driven K+ accumulation in the T-tubular space. A reduced form of model is presented in which a two-dimensional phase-plane analysis shows graphically how this diversity of after-responses arises as extracellular [K+] and the proportion of noninactivating sodium channels are varied.

Animals↗

Combining the lattice-sum and reaction-field approaches for evaluating long-range electrostatic interactions in molecular simulations.

A new scheme, the lattice-sum-emulated reaction-field (LSERF) method, is presented that combines the lattice-sum (LS) and reaction-field (RF) approaches for evaluating electrostatic interactions in molecular simulations. More precisely, the LSERF scheme emulates a RF calculation (based on an atomic cutoff) via the LS machinery. This is achieved by changing the form of the electrostatic interactions in a standard LS calculation (Coulombic) to the form corresponding to RF electrostatics (Coulombic plus quadratic reaction-field correction term, truncated at the cutoff distance). It is shown (both analytically and numerically) that in the limit of infinite reciprocal-space accuracy, (i) the LSERF scheme with a finite reaction-field cutoff and a given reaction-field permittivity is identical to the RF scheme with the same parameters (and an atomic cutoff), and (ii) the LSERF scheme is identical to the LS scheme in the limit of an infinite reaction-field cutoff, irrespective of the reaction-field permittivity. This new scheme offers two key advantages: (i) from a conceptual point of view, it shows that there is a continuity between the RF and LS schemes and unifies them into a common framework; (ii) from a practical point of view, it allows us to perform RF calculations with arbitrarily large reaction-field cutoff distances for the same computational costs as a corresponding LS calculation. The optimal choice for the cutoff will be the one that achieves the best compromise between artifacts arising from the dielectric heterogeneity of the system (short cutoff) and its artificial periodicity (long cutoff). The implementation of the LSERF method is extremely easy, requiring only very limited modifications of any standard LS code. For practical applications to biomolecular systems, the use of the LSERF scheme with large reaction-field cutoff distances is expected to represent a significant improvement over the current RF simulations involving comparatively much shorter cutoffs.

Journal Article↗

A generalized discrete model linking rippling pattern formation and individual cell reversal statistics in colonies of myxobacteria.

Self-organization processes in multicellular aggregates of bacteria and amoebae offer fascinating insights into the evolution of cooperation and differentiation of cells. During myxobacterial development a variety of spatio-temporal patterns emerges such as counterpropagating waves of cell density that are known as rippling. Recently, several models have been introduced that qualitatively reproduce these patterns. All models include active motion and a collision-triggered reversal of individual bacteria. Here, we present a systematic study of a generalized discrete model that is based on similar assumptions as the continuous model by Igoshin et al (2001 Proc. Natl Acad. Sci. USA 98 14913). We find counterpropagating as well as unidirectional rippling waves in extended regions of the parameter space. If the interaction strength and the degree of cooperativity are large enough, rippling patterns appear even in the absence of a refractory period. We show for the first time that the experimentally observed double peak in the reversal statistics of bacteria in rippling colonies (Welch and Kaiser 2001 Proc. Natl Acad. Sci. USA 98 14907) can be reproduced in simulations of counterpropagating rippling waves which are dominant in experiments. In addition, the reversal statistics in the pre-rippling phase is correctly reproduced.

Biological Evolution↗