In silico identification and three-dimensional modelling of the missense mutation in ADAMTS2 in a sheep flock with dermatosparaxis

Background Dermatosparaxis (Ehlers–Danlos syndrome in humans) is characterized by extreme fragility of the skin. It is due to the lack of mature collagen caused by a failure in the enzymatic processing of procollagen I. We investigated the condition in a commercial sheep flock. Hypothesis/Objectives Mutations in the ADAM metallopeptidase with thrombospondin type 1 motif, 2 (ADAMTS2) locus, are involved in the development of dermatosparaxis in humans, cattle and the dorper sheep breed; consequently, this locus was investigated in the flock. Animals A single affected lamb, its dam, the dam of a second affected lamb and the rams in the flock were studied. Methods DNA was purified from blood, PCR primers were used to detect parts of the ADAMS2 gene and nucleotide sequencing was performed using Sanger's procedure. Skin samples were examined using standard histology procedures. Results A missense mutation was identified in the catalytic domain of ADAMTS2. The mutation is predicted to cause the substitution in the mature ADAMTS2 of a valine molecule by a methionine molecule (V15M) affecting the catalytic domain of the enzyme. Both the ‘sorting intolerant from tolerant’ (SIFT) and the PolyPhen-2 methodologies predicted a damaging effect for the mutation. Three-dimensional modelling suggested that this mutation may alter the stability of the protein folding or distort the structure, causing the protein to malfunction. Conclusions and clinical importance Detection of the mutation responsible for the pathology allowed us to remove the heterozygote ram, thus preventing additional cases in the flock.

Simple method for sub-diffraction resolution imaging of cellular structures on standard confocal microscopes by three-photon absorption of quantum dots

This study describes a simple technique that improves a recently developed 3D sub-diffraction imaging method based on three-photon absorption of commercially available quantum dots. The method combines imaging of biological samples via tri-exciton generation in quantum dots with deconvolution and spectral multiplexing, resulting in a novel approach for multi-color imaging of even thick biological samples at a 1.4 to 1.9-fold better spatial resolution. This approach is realized on a conventional confocal microscope equipped with standard continuous-wave lasers. We demonstrate the potential of multi-color tri-exciton imaging of quantum dots combined with deconvolution on viral vesicles in lentivirally transduced cells as well as intermediate filaments in three-dimensional clusters of mouse-derived neural stem cells (neurospheres) and dense microtubuli arrays in myotubes formed by stacks of differentiated C2C12 myoblasts.

Disparity-defined objects moving in depth do not elicit three-dimensional shape constancy

Observers generally fail to recover three-dimensional shape accurately from binocular disparity. Typically, depth is overestimated at near distances and underestimated at far distances [Johnston, E. B. (1991). Systematic distortions of shape from stereopsis. Vision Research, 31, 1351–1360]. A simple prediction from this is that disparity-defined objects should appear to expand in depth when moving towards the observer, and compress in depth when moving away. However, additional information is provided when an object moves from which 3D Euclidean shape can be recovered, be this through the addition of structure from motion information [Richards, W. (1985). Structure from stereo and motion. Journal of the Optical Society of America A, 2, 343–349], or the use of non-generic strategies [Todd, J. T., & Norman, J. F. (2003). The visual perception of 3-D shape from multiple cues: Are observers capable of perceiving metric structure? Perception and Psychophysics, 65, 31–47]. Here, we investigated shape constancy for objects moving in depth. We found that to be perceived as constant in shape, objects needed to contract in depth when moving toward the observer, and expand in depth when moving away, countering the effects of incorrect distance scaling (Johnston, 1991). This is a striking example of the failure of shape con- stancy, but one that is predicted if observers neither accurately estimate object distance in order to recover Euclidean shape, nor are able to base their responses on a simpler processing strategy.

A moving observer in a three-dimensional world

For many tasks, such as retrieving a previously viewed object, an observer must form a representation of the world at one location and use it at another. A world-based 3D reconstruction of the scene built up from visual information would fulfil this requirement, something computer vision now achieves with great speed and accuracy. However, I argue that it is neither easy nor necessary for the brain to do this. I discuss biologically plausible alternatives, including the possibility of avoiding 3D coordinate frames such as ego-centric and world-based representations. For example, the distance, slant and local shape of surfaces dictate the propensity of visual features to move in the image with respect to one another as the observer’s perspective changes (through movement or binocular viewing). Such propensities can be stored without the need for 3D reference frames. The problem of representing a stable scene in the face of continual head and eye movements is an appropriate starting place for understanding the goal of 3D vision, more so, I argue, than the case of a static binocular observer.

A three-dimensional magnetometer for motion sensing of a balloon-carried atmospheric measurement package

An instrument is described which carries three orthogonal geomagnetic field sensors on a standard meteorological balloon package, to sense rapid motion and position changes during ascent through the atmosphere. Because of the finite data bandwidth available over the UHF radio link, a burst sampling strategy is adopted. Bursts of 9s of measurements at 3.6Hz are interleaved with periods of slow data telemetry lasting 25s. Calculation of the variability in each channel is used to determine position changes, a method robust to periods of poor radio signals. During three balloon ascents, variability was found repeatedly at similar altitudes, simultaneously in each of three orthogonal sensors carried. This variability is attributed to atmospheric motions. It is found that the vertical sensor is least prone to stray motions, and that the use of two horizontal sensors provides no additional information over a single horizontal sensor

Variability of the Atlantic thermohaline circulation described by three-dimensional empirical orthogonal functions

We describe the use of bivariate 3d empirical orthogonal functions (EOFs) in characterising low frequency variability of the Atlantic thermohaline circulation (THC) in the Hadley Centre global climate model, HadCM3. We find that the leading two modes are well correlated with an index of the meridional overturning circulation (MOC) on decadal timescales, with the leading mode alone accounting for 54% of the decadal variance. Episodes of coherent oscillations in the sub-space of the leading EOFs are identified; these episodes are of great interest for the predictability of the THC, and could indicate the existence of different regimes of natural variability. The mechanism identified for the multi-decadal variability is an internal ocean mode, dominated by changes in convection in the Nordic Seas, which lead the changes in the MOC by a few years. Variations in salinity transports from the Arctic and from the North Atlantic are the main feedbacks which control the oscillation. This mode has a weak feedback onto the atmosphere and hence a surface climatic influence. Interestingly, some of these climate impacts lead the changes in the overturning. There are also similarities to observed multi-decadal climate variability.

Monitoring and modelling the three-dimensional flow of water under drip irrigation

The interpretation of soil water dynamics under drip irrigation systems is relevant for crop production as well as on water use and management. In this study a three-dimensional representation of the flow of water under drip irrigation is presented. The work includes analysis of the water balance at point scale as well as area-average, exploring uncertainties in water balance estimations depending on the number of locations sampled. The water flow was monitored by detailed profile water content measurements before irrigation, after irrigation and 24 h later with a dense array of soil moisture access tubes radially distributed around selected drippers. The objective was to develop a methodology that could be used on selected occasions to obtain 'snap shots' of the detailed three-dimensional patterns of soil moisture. Such patterns are likely to be very complex, as spatial variability will be induced for a number of reasons, such as strong horizontal gradients in soil moisture, variations between individual sources in the amount of water applied and spatial variability is soil hydraulic properties. Results are compared with a widely used numerical model, Hydrus-2D. The observed dynamic of the water content distribution is in good agreement with model simulations, although some discrepancies concerning the horizontal distribution of the irrigation bulb are noted due to soil heterogeneity. (c) 2006 Elsevier B.V. All rights reserved.

The three-dimensional vortical nature of atmospheric and oceanic turbulent flows

Using a novel numerical method at unprecedented resolution, we demonstrate that structures of small to intermediate scale in rotating, stratified flows are intrinsically three-dimensional. Such flows are characterized by vortices (spinning volumes of fluid), regions of large vorticity gradients, and filamentary structures at all scales. It is found that such structures have predominantly three-dimensional dynamics below a horizontal scale LLR, where LR is the so-called Rossby radius of deformation, equal to the characteristic vertical scale of the fluid H divided by the ratio of the rotational and buoyancy frequencies f/N. The breakdown of two-dimensional dynamics at these scales is attributed to the so-called "tall-column instability" [D. G. Dritschel and M. de la Torre Juárez, J. Fluid. Mech. 328, 129 (1996)], which is active on columnar vortices that are tall after scaling by f/N, or, equivalently, that are narrow compared with LR. Moreover, this instability eventually leads to a simple relationship between typical vertical and horizontal scales: for each vertical wave number (apart from the vertically averaged, barotropic component of the flow) the average horizontal wave number is equal to f/N times the vertical wave number. The practical implication is that three-dimensional modeling is essential to capture the behavior of rotating, stratified fluids. Two-dimensional models are not valid for scales below LR. ©1999 American Institute of Physics.

A well-posed integral equation formulation for three-dimensional rough surface scattering

We consider the problem of scattering of time-harmonic acoustic waves by an unbounded sound-soft rough surface. Recently, a Brakhage Werner type integral equation formulation of this problem has been proposed, based on an ansatz as a combined single- and double-layer potential, but replacing the usual fundamental solution of the Helmholtz equation with an appropriate half-space Green's function. Moreover, it has been shown in the three-dimensional case that this integral equation is uniquely solvable in the space L-2 (Gamma) when the scattering surface G does not differ too much from a plane. In this paper, we show that this integral equation is uniquely solvable with no restriction on the surface elevation or slope. Moreover, we construct explicit bounds on the inverse of the associated boundary integral operator, as a function of the wave number, the parameter coupling the single- and double-layer potentials, and the maximum surface slope. These bounds show that the norm of the inverse operator is bounded uniformly in the wave number, kappa, for kappa > 0, if the coupling parameter h is chosen proportional to the wave number. In the case when G is a plane, we show that the choice eta = kappa/2 is nearly optimal in terms of minimizing the condition number.

Acoustic scattering by mildly rough unbounded surfaces in three dimensions

For a nonlocally perturbed half- space we consider the scattering of time-harmonic acoustic waves. A second kind boundary integral equation formulation is proposed for the sound-soft case, based on a standard ansatz as a combined single-and double-layer potential but replacing the usual fundamental solution of the Helmholtz equation with an appropriate half- space Green's function. Due to the unboundedness of the surface, the integral operators are noncompact. In contrast to the two-dimensional case, the integral operators are also strongly singular, due to the slow decay at infinity of the fundamental solution of the three-dimensional Helmholtz equation. In the case when the surface is sufficiently smooth ( Lyapunov) we show that the integral operators are nevertheless bounded as operators on L-2(Gamma) and on L-2(Gamma G) boolean AND BC(Gamma) and that the operators depend continuously in norm on the wave number and on G. We further show that for mild roughness, i.e., a surface G which does not differ too much from a plane, the boundary integral equation is uniquely solvable in the space L-2(Gamma) boolean AND BC(Gamma) and the scattering problem has a unique solution which satisfies a limiting absorption principle in the case of real wave number.

Parcel theory in three dimensions and the calculation of SCAPE

Slantwise convective available potential energy (SCAPE) is a measure of the degree to which the atmosphere is unstable to conditional symmetric instability (CSI). It has, until now, been defined by parcel theory in which the atmosphere is assumed to be nonevolving and balanced, that is, two-dimensional. When applying this two-dimensional theory to three-dimensional evolving flows, these assumptions can be interpreted as an implicit assumption that a timescale separation exists between a relatively rapid timescale for slantwise ascent and a slower timescale for the development of the system. An approximate extension of parcel theory to three dimensions is derived and it is shown that calculations of SCAPE based on the assumption of relatively rapid slantwise ascent can be qualitatively in error. For a case study example of a developing extratropical cyclone, SCAPE calculated along trajectories determined without assuming the existence of the timescale separation show large SCAPE values for parcels ascending from the warm sector and along the warm front. These parcels ascend into the cloud head within which there is some evidence consistent with the release of CSI from observational and model cross sections. This region of high SCAPE was not found for calculations along the relatively rapidly ascending trajectories determined by assuming the existence of the timescale separation.

4,4 '-Dipyridyl-N,N '-dioxide complexes of metal-thiocyanate/selenocyanate: pi-stacked molecular rods as three-dimensional support for two-dimensional polymeric sheets and intra/interchain S center dot center dot center dot S interaction dependent architecture of the R-2(2)(8) synthon driven assembly of one-dimensional polymeric chains

Three supramolecular complexes of Co(II) using SCN-/SeCN- in combination with 4,4'-dipyridyl-N,N'-dioxide (dpyo), i.e., {[Co(SCN)(2)(dpyo)(2)].(dpyo)}(n) ( 1), {[Co(SCN)(2)(dpyo)(H2O)(2)].(H2O)}(n) ( 2), {[Co(SeCN)(2)(dpyo)(H2O)(2)]center dot(H2O)}(n) ( 3), have been synthesized and characterized by single-crystal X-ray analysis. Complex 1 is a rare example of a dpyo bridged two-dimensional (2D) coordination polymer, and pi-stacked dpyo supramolecular rods are generated by the lattice dpyo, passing through the rhombic grid of stacked layers, resulting in a three-dimensional (3D) superstructure. Complexes 2 and 3 are isomorphous one-dimensional (1D) coordination polymers [-Co-dpyo-Co-] that undergo self-assembly leading to a bilayer architecture derived through an R-2(2)(8) H-bonding synthon between coordinated water and dpyo oxygen. A reinvestigation of coordination polymers [Mn(SCN)(2)(dpyo)( H2O)(MeOH)](n) ( 4) and {[Fe(SCN)(2)(dpyo)(H2O)(2)]center dot(H2O)}(n) ( 5) reported recently by our group [ Manna et al. Indian J. Chem. 2006, 45A, 1813] reveals brick wall topology rather than bilayer architecture is due to the decisive role of S center dot center dot center dot S/Se center dot center dot center dot Se interactions in determining the helical nature in 4 and 5 as compared to zigzag polymeric chains in 2 and 3, although the same R-2(2)(8) synthon is responsible for supramolecular assembly in these complexes.

Macrocyclic amines as structure-directing agents for the synthesis of three-dimensional antimony-sulfide frameworks

A new family of antimony sulfides, incorporating the macrocyclic tetramine 1,4,8,11-tetraazacyclotetradecane ( cyclam), has been prepared by a hydrothermal method. [C10N4H26][Sb4S7] (1), [Ni(C10N4H24)][Sb4S7] (2), and [Co(C10N4H24)](x)[C10N4H26](1-x)[Sb4S7] (0.08 <= x <= 0.74) (3) have been characterized by single-crystal X-ray diffraction, elemental analysis, thermogravimetry, and analytical electron microscopy. All three materials possess the same novel three-dimensional Sb4S72- framework, constructed from layers of parallel arrays of Sb4S84- chains stacked at 90 to one another. In 1, doubly protonated macrocyclic cations reside in the channel structure of the antimonysulfide framework. In 2 and 3, the cyclam acts as a ligand, chelating the divalent transition- metal cation. Analytical and X-ray diffraction data indicate that the level of metal incorporation in 2 is effectively complete, whereas in 3, both metalated and nonmetalated forms of the macrocycle coexist within the structure.

Three dimensional picture of the local structure of 1,4-Polybutadiene from a complete atomistic model and neutron scattering data

An efficient method of combining neutron diffraction data over an extended Q range with detailed atomistic models is presented. A quantitative and qualitative mapping of the organization of the chain conformation in both glass and liquid phase has been performed. The proposed structural refinement method is based on the exploitation of the intrachain features of the diffraction pattern by the use of internal coordinates for bond lengths, valence angles and torsion rotations. Models are built stochastically by assignment of these internal coordinates from probability distributions with limited variable parameters. Variation of these parameters is used in the construction of models that minimize the differences between the observed and calculated structure factors. A series of neutron scattering data of 1,4-polybutadiene at the region 20320 K is presented. Analysis of the experimental data yield bond lengths for C-C and C=C of 1.54 and 1.35 Å respectively. Valence angles of the backbone were found to be at 112 and 122.8 for the CCC and CC=C respectively. Three torsion angles corresponding to the double bond and the adjacent R and β bonds were found to occupy cis and trans, s(, trans and g( and trans states, respectively. We compare our results with theoretical predictions, computer simulations, RIS models, and previously reported experimental results.

Three-dimensional random Voronoi tessellations: From cubic crystal lattices to Poisson point processes

We perturb the SC, BCC, and FCC crystal structures with a spatial Gaussian noise whose adimensional strength is controlled by the parameter a, and analyze the topological and metrical properties of the resulting Voronoi Tessellations (VT). The topological properties of the VT of the SC and FCC crystals are unstable with respect to the introduction of noise, because the corresponding polyhedra are geometrically degenerate, whereas the tessellation of the BCC crystal is topologically stable even against noise of small but finite intensity. For weak noise, the mean area of the perturbed BCC and FCC crystals VT increases quadratically with a. In the case of perturbed SCC crystals, there is an optimal amount of noise that minimizes the mean area of the cells. Already for a moderate noise (a>0.5), the properties of the three perturbed VT are indistinguishable, and for intense noise (a>2), results converge to the Poisson-VT limit. Notably, 2-parameter gamma distributions are an excellent model for the empirical of of all considered properties. The VT of the perturbed BCC and FCC structures are local maxima for the isoperimetric quotient, which measures the degre of sphericity of the cells, among space filling VT. In the BCC case, this suggests a weaker form of the recentluy disproved Kelvin conjecture. Due to the fluctuations of the shape of the cells, anomalous scalings with exponents >3/2 is observed between the area and the volumes of the cells, and, except for the FCC case, also for a->0. In the Poisson-VT limit, the exponent is about 1.67. As the number of faces is positively correlated with the sphericity of the cells, the anomalous scaling is heavily reduced when we perform powerlaw fits separately on cells with a specific number of faces.