Design of artificial myocardial microtissues

Cultivation technologies promoting organization of mammalian cells in three dimensions are essential for gene-function analyses as well as drug testing and represent the first step toward the design of tissue replacements and bioartificial organs. Embedded in a three-dimensional environment, cells are expected to develop tissue-like higher order intercellular structures (cell-cell contacts, extracellular matrix) that orchestrate cellular functions including proliferation, differentiation, apoptosis, and angiogenesis with unmatched quality. We have refined the hanging drop cultivation technology to pioneer beating heart microtissues derived from pure primary rat and mouse cardiomyocyte cultures as well as mixed populations reflecting the cell type composition of rodent hearts. Phenotypic characterization combined with detailed analysis of muscle-specific cell traits, extracellular matrix components, as well as endogenous vascular endothelial growth factor (VEGF) expression profiles of heart microtissues revealed (1) a linear cell number-microtissue size correlation, (2) intermicrotissue superstructures, (3) retention of key cardiomyocyte-specific cell qualities, (4) a sophisticated extracellular matrix, and (5) a high degree of self-organization exemplified by the tendency of muscle structures to assemble at the periphery of these myocardial spheroids. Furthermore (6), myocardial spheroids support endogenous VEGF expression in a size-dependent manner that will likely promote vascularization of heart microtissues produced from defined cell mixtures as well as support connection to the host vascular system after implantation. As cardiomyocytes are known to be refractory to current transfection technologies we have designed lentivirus-based transduction strategies to lead the way for genetic engineering of myocardial microtissues in a clinical setting.

Primary personality trait correlates of religious practice and orientation

The aim of the study was to examine the relationships between Eysenck's primary personality factors and various aspects of religious orientation and practice. Some 400 UK undergraduates completed questionnaires constructed from the Batson and Schoenrade Religious Life Inventory (Batson & Schoenrade, 1991) and the Eysenck Personality Profiler (Eysenck, Barrett, Wilson, & Jackson, 1992). As is generally found, all the religious variables correlated negatively with the higher order personality factor of psychoticism. In contrast, among the primary factors, those associated with neuroticism appeared to be the strongest indicators of religiosity. In particular, all the primary traits classically linked to neuroticism correlate positively with the quest orientation. However, fewer primary traits predict religious behaviour in regression and of these, a sense of guilt is the greatest and a common predictor of extrinsic, intrinsic and quest religiosities. Upon factor analysis of the significant personality predictors together with the three religious orientations, the orientations formed a single discrete factor, which implies that extrinsic, intrinsic and quest religiosities have more in common with one another than with any of the personality traits included in the study. This suggests that religious awareness may itself be an important individual difference that is distinct from those generally associated with models of personality. (C) 2003 Elsevier Ltd. All rights reserved.

Critical fluctuations and entanglement in the nondegenerate parametric oscillator

We present a fully quantum mechanical treatment of the nondegenerate optical parametric oscillator both below and near threshold. This is a nonequilibrium quantum system with a critical point phase transition, that is also known to exhibit strong yet easily observed squeezing and quantum entanglement. Our treatment makes use of the positive P representation and goes beyond the usual linearized theory. We compare our analytical results with numerical simulations and find excellent agreement. We also carry out a detailed comparison of our results with those obtained from stochastic electrodynamics, a theory obtained by truncating the equation of motion for the Wigner function, with a view to locating regions of agreement and disagreement between the two. We calculate commonly used measures of quantum behavior including entanglement, squeezing, and Einstein-Podolsky-Rosen (EPR) correlations as well as higher order tripartite correlations, and show how these are modified as the critical point is approached. These results are compared with those obtained using two degenerate parametric oscillators, and we find that in the near-critical region the nondegenerate oscillator has stronger EPR correlations. In general, the critical fluctuations represent an ultimate limit to the possible entanglement that can be achieved in a nondegenerate parametric oscillator.

Three-dimensional solitons in coupled atomic-molecular Bose-Einstein condensates

We present a theoretical analysis of three-dimensional (3D) matter-wave solitons and their stability properties in coupled atomic and molecular Bose-Einstein condensates (BECs). The soliton solutions to the mean-field equations are obtained in an approximate analytical form by means of a variational approach. We investigate soliton stability within the parameter space described by the atom-molecule conversion coupling, the atom-atom s-wave scattering, and the bare formation energy of the molecular species. In terms of ordinary optics, this is analogous to the process of sub- or second-harmonic generation in a quadratic nonlinear medium modified by a cubic nonlinearity, together with a phase mismatch term between the fields. While the possibility of formation of multidimensional spatiotemporal solitons in pure quadratic media has been theoretically demonstrated previously, here we extend this prediction to matter-wave interactions in BEC systems where higher-order nonlinear processes due to interparticle collisions are unavoidable and may not be neglected. The stability of the solitons predicted for repulsive atom-atom interactions is investigated by direct numerical simulations of the equations of motion in a full 3D lattice. Our analysis also leads to a possible technique for demonstrating the ground state of the Schrodinger-Newton and related equations that describe Bose-Einstein condensates with nonlocal interparticle forces.

The role of drinking restraint in alcohol dependence: validation of the temptation and restraint inventory in an alcohol dependent sample

Objective: The Temptation and Restraint Inventory (TRI) is commonly used to measure drinking restraint in relation to problem drinking behavior. However, as yet the TRI has not been validated in a clinical group with alcohol dependence. Method: Male (n = 111) and female (n = 57) inpatients with DSM-IV diagnosed alcohol dependence completed the TRI and measures of problem drinking severity, including the Alcohol Dependence Scale and the quantity, frequency and week total of alcohol consumed. Results: The factor structure of the TRI was replicated in the alcohol dependent sample. Cognitive Emotional Preoccupation (CEP), one of the two higher order factors of the TRI, demonstrated sound predictive power toward all dependence severity indices. The other higher order factor, Cognitive Behavioral Control (CBC), was related to frequency of drinking. There was limited support for the CEP/CBC interactional model of drinking restraint. Conclusions: Although the construct validity of the TRI was sound, the measure appears more useful in understanding the development, maintenance and severity of alcohol-related problems in nondependent drinkers. The TRI may show promise in detecting either continuous drinking or heavy episodic type dependent drinkers.

A parent-report measure of children's anxiety: psychometric properties and comparison with child-report in a clinic and normal sample

This study examined the psychometric properties of the parent version of the Spence Children's Anxiety Scale (SCAS-P); 484 parents of anxiety disordered children and 261 parents in a normal control group participated in the study. Results of confirmatory factor analysis provided support for six intercorrelated factors, that corresponded with the child self-report as well as with the classification of anxiety disorders by DSM-IV (namely separation anxiety, generalized anxiety, social phobia, panic/agoraphobia, obsessive-compulsive disorder, and fear of physical injuries). A post-hoc model in which generalized anxiety functioned as the higher order factor for the other five factors described the data equally well. The reliability of the subscales was satisfactory to excellent. Evidence was found for both convergent and divergent validity: the measure correlated well with the parent report for internalizing symptoms, and lower with externalizing symptoms. Parent-child agreement ranged from 0.41 to 0.66 in the anxiety-disordered group, and from 0.23 to 0.60 in the control group. The measure differentiated significantly between anxiety-disordered children versus controls, and also between the different anxiety disorders except GAD. The SCAS-P is recommended as a screening instrument for normal children and as a diagnostic instrument in clinical settings. (C) 2003 Elsevier Ltd. All rights reserved.

Minimal instrumentation may compromise failure diagnosis with an ecological interface

Interfaces designed according to ecological interface design (EID) display higher-order relations and properties of a work domain so that adaptive operator problem solving can be better supported under unanticipated system conditions. Previous empirical studies of EID have assumed that the raw data required to derive and communicate higher-order information would be available and reliable. The present research examines the relative advantages of an EID interface over a conventional piping-and-instrumentation diagram (PID) when instrumentation is maximally or only minimally adequate. Results show an interaction between interface and the adequacy of the instrumentation. Failure diagnosis performance with the EID interface with maximally adequate instrumentation is best overall. Performance with the EID interface drops more drastically from maximally to minimally adequate instrumentation than does performance with the PID interface, to the point where the EID interface with minimally adequate instrumentation supports nonsignificantly worse performance than does the equivalent PID interface. Actual or potential applications of this research include design of instrumentation and displays for complex industrial processes.

Three distinct molecular surfaces in ephrin-A5 are essential for a functional interaction with EphA3

Eph receptor tyrosine kinases (Ephs) function as molecular relays that interact with cell surface-bound ephrin ligands to direct the position of migrating cells. Structural studies revealed that, through two distinct contact surfaces on opposite sites of each protein, Eph and ephrin binding domains assemble into symmetric, circular heterotetramers. However, Eph signal initiation requires the assembly of higher order oligomers, suggesting additional points of contact. By screening a random library of EphA3 binding-compromised ephrin-A5 mutants, we have now determined ephrin-A5 residues that are essential for the assembly of high affinity EphA3 signaling complexes. In addition to the two interfaces predicted from the crystal structure of the homologous EphB2 center dot ephrin-B2 complex, we identified a cluster of 10 residues on the ephrin-A5 E alpha-helix, the E-F loop, the underlying H beta-strand, as well as the nearby B - C loop, which define a distinct third surface required for oligomerization and activation of EphA3 signaling. Together with a corresponding third surface region identified recently outside of the minimal ephrin binding domain of EphA3, our findings provide experimental evidence for the essential contribution of three distinct protein-interaction interfaces to assemble functional EphA3 signaling complexes.

New approximation for free surface flow of groundwater: capillarity correction

An existing capillarity correction for free surface groundwater flow as modelled by the Boussinesq equation is re-investigated. Existing solutions, based on the shallow flow expansion, have considered only the zeroth-order approximation. Here, a second-order capillarity correction to tide-induced watertable fluctuations in a coastal aquifer adjacent to a sloping beach is derived. A new definition of the capillarity correction is proposed for small capillary fringes, and a simplified solution is derived. Comparisons of the two models show that the simplified model can be used in most cases. The significant effects of higher-order capillarity corrections on tidal fluctuations in a sloping beach are also demonstrated. (c) 2004 Elsevier Ltd. All rights reserved.

Better prediction of protein contact number using a support vector regression analysis of amino acid sequence

Background: Protein tertiary structure can be partly characterized via each amino acid's contact number measuring how residues are spatially arranged. The contact number of a residue in a folded protein is a measure of its exposure to the local environment, and is defined as the number of C-beta atoms in other residues within a sphere around the C-beta atom of the residue of interest. Contact number is partly conserved between protein folds and thus is useful for protein fold and structure prediction. In turn, each residue's contact number can be partially predicted from primary amino acid sequence, assisting tertiary fold analysis from sequence data. In this study, we provide a more accurate contact number prediction method from protein primary sequence. Results: We predict contact number from protein sequence using a novel support vector regression algorithm. Using protein local sequences with multiple sequence alignments (PSI-BLAST profiles), we demonstrate a correlation coefficient between predicted and observed contact numbers of 0.70, which outperforms previously achieved accuracies. Including additional information about sequence weight and amino acid composition further improves prediction accuracies significantly with the correlation coefficient reaching 0.73. If residues are classified as being either contacted or non-contacted, the prediction accuracies are all greater than 77%, regardless of the choice of classification thresholds. Conclusion: The successful application of support vector regression to the prediction of protein contact number reported here, together with previous applications of this approach to the prediction of protein accessible surface area and B-factor profile, suggests that a support vector regression approach may be very useful for determining the structure-function relation between primary sequence and higher order consecutive protein structural and functional properties.

Approximating persistence in a general class of population processes

We provide a general framework for estimating persistence in populations which may be affected by catastrophic events, and which are either unbounded or have very large ceilings. We model the population using a birth-death process modified to allow for downward jumps of arbitrary size. For such processes, it is typically necessary to truncate the process in order to make the evaluation of expected extinction times (and higher-order moments) computationally feasible. Hence, we give particular attention to the selection of a cut-off point at which to truncate the process, and we present a simple method for obtaining quantitative indicators of the suitability of a chosen cut-off. (c) 2005 Elsevier Inc. All rights reserved.

Advanced patient monitoring displays: Tools or continuous informing

We reviewed the use of advanced display technologies for monitoring in anesthesia. Researchers are investigating displays that integrate information and that, in some cases, also deliver the results continuously to the anesthesiologist. Integrated visual displays reveal higher-order properties of patient state and speed in responding to events, but their benefits under an intensely timeshared load is unknown. Head-mounted displays seem to shorten the time to respond to changes, but their impact on peripheral awareness and attention is unknown. Continuous auditory displays extending pulse oximetry seem to shorten response times and improve the ability to time-share other tasks, but their integration into the already noisy operative environment still needs to be tested. We reviewed the advantages and disadvantages of the three approaches, drawing on findings from other fields, such as aviation, to suggest outcomes where there are still no results for the anesthesia context. Proving that advanced patient monitoring displays improve patient outcomes is difficult, and a more realistic goal is probably to prove that such displays lead to better situational awareness, earlier responding, and less workload, all of which keep anesthesia practice away from the outer boundaries of safe operation.

Modeling diffraction and imaging of laser beams by the mode-expansion method

We present a new method of modeling imaging of laser beams in the presence of diffraction. Our method is based on the concept of first orthogonally expanding the resultant diffraction field (that would have otherwise been obtained by the laborious application of the Huygens diffraction principle) and then representing it by an effective multimodal laser beam with different beam parameters. We show not only that the process of obtaining the new beam parameters is straightforward but also that it permits a different interpretation of the diffraction-caused focal shift in laser beams. All of the criteria that we have used to determine the minimum number of higher-order modes needed to accurately represent the diffraction field show that the mode-expansion method is numerically efficient. Finally, the characteristics of the mode-expansion method are such that it allows modeling of a vast array of diffraction problems, regardless of the characteristics of the incident laser beam, the diffracting element, or the observation plane. (C) 2005 Optical Society of America.

Brain maps, great and small: lessons from comparative studies of primate visual cortical organization

In this paper, we review evidence from comparative studies of primate cortical organization, highlighting recent findings and hypotheses that may help us to understand the rules governing evolutionary changes of the cortical map and the process of formation of areas during development. We argue that clear unequivocal views of cortical areas and their homologies are more likely to emerge for 'core' fields, including the primary sensory areas, which are specified early in development by precise molecular identification steps. In primates, the middle temporal area is probably one of these primordial cortical fields. Areas that form at progressively later stages of development correspond to progressively more recent evolutionary events, their development being less firmly anchored in molecular specification. The certainty with which areal boundaries can be delimited, and likely homologies can be assigned, becomes increasingly blurred in parallel with this evolutionary/developmental sequence. For example, while current concepts for the definition of cortical areas have been vindicated in allowing a clarification of the organization of the New World monkey 'third tier' visual cortex (the third and dorsomedial areas, V3 and DM), our analyses suggest that more flexible mapping criteria may be needed to unravel the organization of higher-order visual association and polysensory areas.

Analysis of the effect of transverse modes on free-space optical interconnect performance

Vertical-cavity surface-emitting lasers (VCSELs) and microlenses can be used to implement free space optical interconnects (FSOIs) which do not suffer from the bandwidth limitations inherent in metallic interconnects. A comprehensive link equation describing the effects of both optical and electrical noise is introduced. We have evaluated FSOI performance by examining the following metrics: the space-bandwidth product (SBP), describing the density of channels and aggregate bandwidth that can be achieved, and the carrier-to-noise ratio (CNR), which represents the relative strength of the carrier signal. The mode expansion method (MEM) was used to account for the primary cause of optical noise: laser beam diffraction. While the literature commonly assumes an ideal single-mode laser beam, we consider the experimentally determined multimodal structure of a VCSEL beam in our calculations. It was found that maximum achievable interconnect length and density for a given CNR was significantly reduced when the higher order transverse modes were present in Simulations. However, the Simulations demonstrate that free-space optical interconnects are still a suitable solution for the communications bottleneck, despite the adverse effects introduced by transverse modes.