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Sensitivity of ecological models to their climate drivers: statistical ensembles for forcing.

Global and regional numerical models for terrestrial ecosystem dynamics require fine spatial resolution and temporally complete historical climate fields as input variables. However, because climate observations are unevenly spaced and have incomplete records, such fields need to be estimated. In addition, uncertainty in these fields associated with their estimation are rarely assessed. Ecological models are usually driven with a geostatistical model's mean estimate (kriging) of these fields without accounting for this uncertainty, much less evaluating such errors in terms of their propagation in ecological simulations. We introduce a Bayesian statistical framework to model climate observations to create spatially uniform and temporally complete fields, taking into account correlation in time and space, spatial heterogeneity, lack of normality, and uncertainty about all these factors. A key benefit of the Bayesian model is that it generates uncertainty measures for the generated fields. To demonstrate this method, we reconstruct historical monthly precipitation fields (a driver for ecological models) on a fine resolution grid for a climatically heterogeneous region in the western United States. The main goal of this work is to evaluate the sensitivity of ecological models to the uncertainty associated with prediction of their climate drivers. To assess their numerical sensitivity to predicted input variables, we generate a set of ecological model simulations run using an ensemble of different versions of the reconstructed fields. We construct such an ensemble by sampling from the posterior predictive distribution of the climate field. We demonstrate that the estimated prediction error of the climate field can be very high. We evaluate the importance of such errors in ecological model experiments using an ensemble of historical precipitation time series in simulations of grassland biogeochemical dynamics with an ecological numerical model, Century. We show how uncertainty in predicted precipitation fields is propagated into ecological model results and that this propagation had different modes. Depending on output variable, the response of model dynamics to uncertainty in inputs ranged from uncertainty in outputs that matched that of inputs to those that were muted or that were biased, as well as uncertainty that was persistent in time after input errors dropped.

Animals↗

Elastic model-based segmentation of 3-D neuroradiological data sets.

This paper presents a new technique for the automatic model-based segmentation of three-dimensional (3-D) objects from volumetric image data. The development closely follows the seminal work of Taylor and Cootes on active shape models, but is based on a hierarchical parametric object description rather than a point distribution model. The segmentation system includes both the building of statistical models and the automatic segmentation of new image data sets via a restricted elastic deformation of shape models. Geometric models are derived from a sample set of image data which have been segmented by experts. The surfaces of these binary objects are converted into parametric surface representations, which are normalized to get an invariant object-centered coordinate system. Surface representations are expanded into series of spherical harmonics which provide parametric descriptions of object shapes. It is shown that invariant object surface parametrization provides a good approximation to automatically determine object homology in terms of sets of corresponding sets of surface points. Gray-level information near object boundaries is represented by 1-D intensity profiles normal to the surface. Considering automatic segmentation of brain structures as our driving application, our choice of coordinates for object alignment was the well-accepted stereotactic coordinate system. Major variation of object shapes around the mean shape, also referred to as shape eigenmodes, are calculated in shape parameter space rather than the feature space of point coordinates. Segmentation makes use of the object shape statistics by restricting possible elastic deformations into the range of the training shapes. The mean shapes are initialized in a new data set by specifying the landmarks of the stereotactic coordinate system. The model elastically deforms, driven by the displacement forces across the object's surface, which are generated by matching local intensity profiles. Elastic deformations are limited by setting bounds for the maximum variations in eigenmode space. The technique has been applied to automatically segment left and right hippocampus, thalamus, putamen, and globus pallidus from volumetric magnetic resonance scans taken from schizophrenia studies. The results have been validated by comparison of automatic segmentation with the results obtained by interactive expert segmentation.

Algorithms↗

Scopes of perception: the experimental manipulation of space and time.

Discussions of space and time have been grist to the philosophers' mill for centuries. We argue that the evolution of psychology as an independent discipline was in part a consequence of addressing philosophical questions concerning the perception of space and time by recourse to experiment rather than exposition. Two initially separate factors assisted in establishing this independence. On the one hand, it was driven by the invention of instruments for stimulus control so that the methods of physics could be applied to the study of perceptual phenomena. On the other hand and somewhat later, it was followed by the development of psychophysical methods, which opened the possibility of quantifying the responses to such controlled stimulation. The principal instruments were invented in the first half of the nineteenth century, and they consisted of simple contrivances that manipulated time and space in ways that had not previously been appreciated. This article examines the devices that were invented, like stroboscopes, anorthoscopes, stereoscopes, tachistoscopes, chronoscopes, and more recently oscilloscopes, and the ways in which they influenced the scope of perceptual psychology in the past as well as in the present. In contemporary experimental psychology all these instruments have been replaced by the computer. While it has extended the scope of experiments even further it has introduced a new set of limitations.

History, 18th Century↗

Light-induced potassium fluxes in the skate retina.

Changes in the extracellular concentration of potassium [K+]0 in response to photic stimulation were studied in the skate retina with the aid of ion-selective electrodes. The results confirm earlier studies in demonstrating that the light-evoked changes originate at three intraretinal sites; an efflux of K+ was recorded in the regions of the two plexiform (synaptic) layers, whereas a decrease in [K+]0 occurred in the extracellular space surrounding the photoreceptors. Prolonged illumination induced long-term alterations in the levels of [K+]0 which, depending upon the retinal depth of the recording electrode, contained contributions from the various sinks and sources of [K+]0. In addition, the marked undershoot of the baseline level of [K+]0 that followed termination of the stimulus suggested the activity of a metabolically driven process for the uptake of extracellular potassium.

Animals↗

Dynamic patterns and self-knotting of a driven hanging chain.

When shaken vertically, a hanging chain displays a startling variety of distinct behaviors. We find experimentally that instabilities occur in tonguelike bands of parameter space, to swinging or rotating pendular motion, or to chaotic states. Mathematically, the dynamics are described by a nonlinear wave equation. A linear stability analysis predicts instabilities within the well-known resonance tongues; their boundaries agree very well with experiment. Full simulations of the 3D dynamics reproduce and elucidate many aspects of the experiment. The chain is also observed to tie knots in itself, some quite complex. This is beyond the reach of the current analysis and simulations.

Journal Article↗

Differential expression of tenascin after denervation, damage or paralysis of mouse soleus muscle.

The expression of the extracellular matrix molecule tenascin was studied by immunocytochemistry and Western blotting in soleus muscles of adult mice after nerve damage (denervation), muscle injury (induced by enforced running or freezing) and functional block of synaptic transmission (botulinum toxin). Enhanced expression of tenascin in the extracellular spaces around focally damaged muscle fibres was found already 10 h after onset of running on a motor-driven treadmill which causes muscle injury in soleus muscle. Tenascin expression reached a peak at 2-3 days post-exercise, after which it declined gradually and became undetectable by two weeks after injury. Similarly, cryo-damage of soleus muscles in situ led to upregulation of tenascin. Chronic muscle denervation after sciatic nerve transection caused a persistent (studied up to 31 days) expression of tenascin at denervated endplates and in intramuscular nerve branches but not in other tissue compartments. Local application of botulinum toxin Type A, which results in muscle inactivity but not in tissue degeneration, however, did not induce tenascin expression 12 h to 12 days post-injection. Expression of tenascin after denervation and muscle damage, but its absence after paralysis, were verified by SDS-PAGE and Western blot analysis. Independent of the type of injury (muscle, nerve or both) the known major isoforms of mouse tenascin, as judged by M(r) comparison, were re-expressed, with no preponderance of individual M(r) forms. These results show that tenascin expression in adult muscles is induced by both axon and muscle fibre damage but not by muscle inactivity. In contrast, NCAM, in accordance with previous observations, showed enhanced expression both as a result of inactivity and in association with tissue repair.

Animals↗

Comparison of the low energy conformations of an oncogenic and a non-oncogenic p21 protein, neither of which binds GTP or GDP.

Oncogenic p21 protein, encoded by the ras-oncogene, that causes malignant transformation of normal cells and many human tumors, is almost identical in sequence to its normal protooncogene-encoded counterpart protein, except for the substitution of arbitrary amino acids for the normally occurring amino acids at critical positions such as Gly 12 and Gln 61. Since p21 is normally activated by the binding of GTP in place of GDP, it has been postulated that oncogenic forms must retain bound GTP for prolonged time periods. However, two multiply substituted p21 proteins have been cloned, neither of which binds GDP or GTP. One of these mutant proteins with Val for Gly 10, Arg for Gly 12, and Thr for Ala 59 causes cell transformation, while the other, similar protein with Gly 10, Arg 12, Val for Gly 13 and Thr 59 does not transform cells. To define the critical conformational changes that occur in the p21 protein that cause it to become oncogenic, we have calculated the low energy conformations of the two multiply substituted mutant p21 proteins using a new adaptation of the electrostatically driven Monte Carlo (EDMC) technique, based on the program ECEPP. We have used this method to explore the conformational space available to both proteins and to compute the average structures for both using statistical mechanical averaging. Comparison of the average structures allows us to detect the major differences in conformation between the two proteins. Starting structures for each protein were calculated using the recently deposited x-ray crystal coordinates for the p21 protein, that was energy-refined using ECEPP, and then perturbed using the EDMC method to compute its average structure. The specific amino acid substitutions for both proteins were then generated into the lowest energy structure generated by this procedure, subjected to energy minimization and then to full EDMC perturbations. We find that both mutant proteins exhibit major differences in conformation in specific regions, viz., residues 35-47, 55-78, 81-93, 96-110, 115-126, and 123-134, compared with the EDMC-refined x-ray structure of the wild-type protein. These regions have been found to be the most flexible in the p21 protein bound to GDP from prior molecular dynamics calculations (Dykes et al., 1993). Comparison of the EDMC-average structure of the transforming mutant with that of the nontransforming mutant reveals major structural differences at residues 10-16, 32-40, and 60-68. These structural differences appear to be the ones that are critical in activation of the p21 protein.(ABSTRACT TRUNCATED AT 400 WORDS)

Crystallography, X-Ray↗

Clinical experience with devices for facilitated anastomoses in coronary artery bypass surgery.

Recent developments in minimally invasive coronary artery surgery have been driven by the introduction of new technologies which should facilitate precise surgical maneuvers on the beating heart within confined spaces. Such technologies include coronary stabilizer systems, cardiac positioning vacuum-assisted devices, and telemanipulative systems. Despite these developments, standard suturing techniques using running polypropylene material remains a limiting factor in the surgeon's ability to perform complete revascularization with high quality anastomoses through minimal approaches to the chest cavity. Clinical validation of proximal and distal anastomotic devices has the potential to substantially improve and perhaps revolutionize minimally invasive coronary surgery. Ideal characteristics of such devices would include applicability to all conduit types, all coronary sizes, interchangeable proximal/distal sequencing of the anastomosis, and safe bail out for device malfunction. However there is an urgent need to define the performance objectives of such systems as well as the general criteria for proper and comparable evaluation and validation of different systems in animal models and subsequently in controlled prospective clinical studies. This review summarizes the most interesting systems available in both experimental and clinical settings.

Anastomosis, Surgical↗

Simple and highly efficient method for transient in vivo gene transfer to mid-late pregnant mouse uterus.

Up- and down-regulation of various genes in the placenta, decidua and amnion has been reported during the mid-late period of pregnancy and in pregnancy-related complications, such as preeclampsia and preterm labor. However, whether this gene regulation at the feto-maternal interface directly influences the physiology/pathophysiology of disease remains unknown. In order to study this problem, transient gene transfer into the pregnant uterus at mid-late term would be a useful tool. We injected exogenous plasmid entrapped using a commercially available Hemagglutinating Virus of Japan Envelope (HVJ-E) vector system (GenomONE Neo, Ishihara Sangyo) into the extra-amniotic space of the upper part of the pregnant mouse uterus on day 14.5 post-coitus (p.c.). Luciferase activity driven by the cytomegalovirus promoter was detectable for 3 days after transfection in the upper, middle and lower part of the uterus. beta-Galactsidase activity was localized in the basal lamina of the placenta, the decidual membrane and the fetal membrane. Exogenous plasmid was not transmitted to the fetus. The course of pregnancy was not disturbed by this procedure; rupture of membranes, intrauterine fetal growth restriction and preterm birth were not observed. Thus, we demonstrated that this transient gene transfer method is highly efficient and minimally invasive, and expect that this procedure will be a useful tool to analyze the pathophysiology of pregnancy-related disorders.

Animals↗

ADAM 12 protease induces adipogenesis in transgenic mice.

ADAM 12 (meltrin-alpha) is a member of the ADAM (a disintegrin and metalloprotease) family. ADAM 12 functions as an active metalloprotease, supports cell adhesion, and has been implicated in myoblast differentiation and fusion. Human ADAM 12 exists in two forms: the prototype membrane-anchored protein, ADAM 12-L, and a shorter secreted form, ADAM 12-S. Here we report the occurrence of adipocytes in the skeletal muscle of transgenic mice in which overexpression of either form is driven by the muscle creatine kinase promoter. Cells expressing a marker of early adipogenesis were apparent in the perivascular space in muscle tissue of 1- to 2-week-old transgenic mice whereas mature lipid-laden adipocytes were seen at 3 to 4 weeks. Moreover, female transgenics expressing ADAM 12-S exhibited increases in body weight, total body fat mass, abdominal fat mass, and herniation, but were normoglycemic and did not exhibit increased serum insulin, cholesterol, or triglycerides. Male transgenics were slightly overweight and also developed herniation but did not become obese. Transgenic mice expressing a truncated form of ADAM 12-S lacking the prodomain and the metalloprotease domain did not develop this adipogenic phenotype, suggesting a requirement for ADAM 12 protease activity. This is the first in vivo demonstration that an ADAM protease is involved in adipogenesis.

ADAM Proteins↗

Subicular cells generate similar spatial firing patterns in two geometrically and visually distinctive environments: comparison with hippocampal place cells.

Cells in both the hippocampus and the subiculum show location related firing patterns, so that the momentary firing rate of a cell is related to the spatial location of a freely moving rat as it navigates in an environment. Since the subiculum receives a strong anatomical projection from the hippocampus, it seems possible that the subicular cell spatial patterns are simply driven by the spatial signals from hippocampal place cells. Data presented here, however, suggest that the two areas code space in fundamentally different ways. Here, spatial firing patterns of individual hippocampal and subicular cells were studied as rats navigated in two different environments. The two chambers were a cylinder and a square, of equal area. For some rats the two chambers were painted to have similar visual stimulus characteristics, while for others, the two were very different. The subicular cells showed very similar firing patterns in the two chambers, regardless of whether they were visually similar or different. In contrast, as predicted based on the findings of earlier studies, hippocampal place cells showed different patterns in the two (again, regardless of their visual similarity). These results suggest that the subicular cells have the ability to transfer a single, abstract spatial representation from one environment to another. This pattern is stretched to fit within the boundaries of the current environment. Thus, the subicular cells seem to provide a generic representation of the geometric relationships between different locations in an environment. It seems possible that this representation may contribute to some navigational abilities exhibited by animals, such as dead reckoning, and novel route generation in unfamiliar environments. In contrast, it appears that hippocampal place cells provide a spatial representation-which is unique for each environment and which is strongly influenced by the exact details and overall context of the situation.

Animals↗

Dynamical tunnelling of ultracold atoms.

The divergence of quantum and classical descriptions of particle motion is clearly apparent in quantum tunnelling between two regions of classically stable motion. An archetype of such non-classical motion is tunnelling through an energy barrier. In the 1980s, a new process, 'dynamical' tunnelling, was predicted, involving no potential energy barrier; however, a constant of the motion (other than energy) still forbids classically the quantum-allowed motion. This process should occur, for example, in periodically driven, nonlinear hamiltonian systems with one degree of freedom. Such systems may be chaotic, consisting of regions in phase space of stable, regular motion embedded in a sea of chaos. Previous studies predicted dynamical tunnelling between these stable regions. Here we observe dynamical tunnelling of ultracold atoms from a Bose-Einstein condensate in an amplitude-modulated optical standing wave. Atoms coherently tunnel back and forth between their initial state of oscillatory motion (corresponding to an island of regular motion) and the state oscillating 180 degrees out of phase with the initial state.

Journal Article↗

Dynamical ensembles in nonequilibrium statistical mechanics and their representations.

The stationary states of driven systems of particles are considered from the point of view of the invariant probability distributions in the phase space which characterize them. The main features of various representations of such distributions are reviewed, and a brief derivation of the one based on orbital measures is given. We mention the limits of the mathematical derivations, and discuss the expected range of applicability beyond such limits. (c) 1998 American Institute of Physics.

Journal Article↗

Statistical mechanical theory for the structure of steady state systems: application to a Lennard-Jones fluid with applied temperature gradient.

The constrained entropy and probability distribution are given for the structure that develops in response to an applied thermodynamic gradient, as occurs in driven steady state systems. The theory is linear but is applicable to gradients with arbitrary spatial variation. The phase space probability distribution is also given, and it is surprisingly simple with a straightforward physical interpretation. With it, all of the known methods of equilibrium statistical mechanics for inhomogeneous systems may now be applied to determining the structure of nonequilibrium steady state systems. The theory is illustrated by performing Monte Carlo simulations on a Lennard-Jones fluid with externally imposed temperature and chemical potential gradients. The induced energy and density moments are obtained, as well as the moment susceptibilities that give the rate of change of these with imposed gradient and which also give the fluctuations in the moments. It is shown that these moment susceptibilities can be written in terms of bulk susceptibilities and also that the Soret coefficient can be expressed in terms of them.

Journal Article↗

The Symmetrytrade mark devices for proximal and distal anastomoses in coronary surgery.

Recent developments in minimally invasive coronary artery surgery have been driven by the introduction of new technologies which should facilitate precise surgical maneuvers on the beating heart within confined spaces. Such technologies include coronary stabilizer systems, cardiac positioning vacuum-assisted devices and, to some extent, telemanipulative systems. Despite these developments, standard suturing techniques using running polypropylene material remain a limiting factor in the surgeon's ability to perform complete revascularization with high quality anastomoses through minimal approaches to the chest cavity. Clinical validation of proximal and distal anastomotic devices has the potential to substantially improve and perhaps revolutionize minimally invasive coronary surgery. Ideal characteristics of such devices would include applicability to all conduit types, all coronary sizes, interchangeable proximal/distal sequencing of the anastomosis and safe bail out for device malfunction. However there is an urgent need to define the performance objectives of such systems as well as the general criteria for proper and comparable evaluation and validation of different systems in animal models and subsequently in controlled prospective clinical studies. In this review, we present different generations of the Symmetrytrade mark devices (ATG, St Jude Medical, St. Paul, MN) for proximal and distal coronary anastomoses.

Journal Article↗

A high yield preparation of brush border membrane vesicles from organ-cultured embryonic chick jejunum: demonstration of insulin sensitivity of Na(+)-dependent D-glucose transport.

Although embryonic chick small intestinal segments provide a very limited amount of tissue for preparation of enterocyte brush border membrane vesicles (BBMV), we were able to develop a procedure for isolation of BBMV from cultured 20-d-old embryonic chick jejunum in high yield by modifying a divalent cation precipitation method. Total yield of the brush border marker enzyme alkaline phosphatase in the vesicle fraction as compared to the crude homogenate was approximately 40%, and the specific activity of the enzyme was increased 25-fold on the average. The brush border membrane vesicle fraction was only contaminated with other cellular organelles (basolateral membranes, mitochondria, lysosomes or endoplasmic reticulum) to a minor extent. Functional integrity of the brush border vesicles was indicated by Na+ gradient-driven electrogenic D-glucose transport leading to concentrative transfer (overshoot) of the sugar into an osmotically active intravesicular space. When jejuna were cultured for 48 h in the presence of 10(-6) mol/L insulin, the initial rate of Na(+)-dependent D-glucose uptake by brush border membrane vesicles as well as Na(+)-dependent [3H]phlorizin binding to brush border membranes was approximately twice as high as in vesicles from untreated controls. This strongly suggests that insulin could enhance intestinal absorption of D-glucose by increasing the intrinsic activity of the Na(+)-dependent D-glucose transport system at the luminal membrane of enterocytes.

Alkaline Phosphatase↗

Discrete soliton ratchets driven by biharmonic fields.

Directed motion of topological solitons (kinks or antikinks) in the damped and ac-driven discrete sine-Gordon system is investigated. We show that if the driving field breaks certain time-space symmetries, the soliton can perform unidirectional motion. The phenomenon resembles the well known effects of ratchet transport and nonlinear harmonic mixing. Direction of the motion and its velocity depends on the shape of the ac drive. Necessary conditions for the occurrence of the effect are formulated. In comparison with the previously studied continuum case, the discrete case shows a number of new features: nonzero depinning threshold for the driving amplitude, locking to the rational fractions of the driving frequency, and diffusive ratchet motion in the case of weak intersite coupling.

Journal Article↗

GenClust: a genetic algorithm for clustering gene expression data.

BACKGROUND: Clustering is a key step in the analysis of gene expression data, and in fact, many classical clustering algorithms are used, or more innovative ones have been designed and validated for the task. Despite the widespread use of artificial intelligence techniques in bioinformatics and, more generally, data analysis, there are very few clustering algorithms based on the genetic paradigm, yet that paradigm has great potential in finding good heuristic solutions to a difficult optimization problem such as clustering. RESULTS: GenClust is a new genetic algorithm for clustering gene expression data. It has two key features: (a) a novel coding of the search space that is simple, compact and easy to update; (b) it can be used naturally in conjunction with data driven internal validation methods. We have experimented with the FOM methodology, specifically conceived for validating clusters of gene expression data. The validity of GenClust has been assessed experimentally on real data sets, both with the use of validation measures and in comparison with other algorithms, i.e., Average Link, Cast, Click and K-means. CONCLUSION: Experiments show that none of the algorithms we have used is markedly superior to the others across data sets and validation measures; i.e., in many cases the observed differences between the worst and best performing algorithm may be statistically insignificant and they could be considered equivalent. However, there are cases in which an algorithm may be better than others and therefore worthwhile. In particular, experiments for GenClust show that, although simple in its data representation, it converges very rapidly to a local optimum and that its ability to identify meaningful clusters is comparable, and sometimes superior, to that of more sophisticated algorithms. In addition, it is well suited for use in conjunction with data driven internal validation measures and, in particular, the FOM methodology.

Algorithms↗