Computational medicine: bioelectric field problems

Applications of large-scale computer modeling and simulation to a class of bioelectric field problems in a variety of biomedical research areas, from single cells to full human structures, are described. The authors focus on a specific subset of bioelectric field problems that have applications in electrocardiography and electroencephalography. The physics and physiology of bioelectric volume conductors are introduced. A specific computational example and the authors' view on the future direction of computational medicine are presented     

A portable cryo-storage system for low-temperature scanning electron microscopy,suitable for international transport of cryo-specimens

A cryo-specimen storage system for low-temperature scanning electron microscopy (LTSEM) specimens is described, which: liberates multi-specimen experiments from sampling restrictions imposed by the rate at which LTSEM specimens can be examined in the SEM; provides security against experiment loss resulting from breakdown of the SEM or cryo-system; enables collection of specimens in the field or in laboratories remote from the SEM laboratory; and facilitates international air transport of LTSEM specimens. The components of the system, which has a capacity of 98 stub-mounted specimens, are readily made in a laboratory workshop. The details of the design may be altered to suit particular specimen types or experimental approaches.     

The domain composition method applied to Poisson's equation in two dimensions

Domain composition, a recently described method for formulating continuum field problems, removes certain restrictions on the construction of finite element models such that it is possible to solve a finite element problem without using a global compatible mesh. The domain composition method couples or otherwise constrains meshes in local regions to obtain a solution equivalent to that produced by conventional finite element methods. In particular, the domain composition method enables finite element models to be formulated with overlapping elements. Several advantages come from this, including an ability to automatically generate a finite element model from a solid geometric model, an ability to use a variety of element types in a single finite element model and an ability to exactly match element boundaries to the local geometry. This paper shows in detail a finite element formulation of Poisson's equation using domain composition and presents certain key algorithms that incorporate the domain composition method into well-established finite element procedures.     

Abnormal behavioral responses to fenfluramine in patients with affective and personality disorders. Correlation with increased serotonergic responsivity

Serotonergic responsivity was assessed in 20 psychiatric patients by the prolactin response to a fenfluramine challenge test. During the fenfluramine challenge 6 of 20 patients (30%) spontaneously reported psychopathologic reactions that included: increased anxiety/agitation, psychotic symptoms, illusions, mood elevation, and anergia. The time of peak behavioral symptoms (2.5 +/- 0.8 hrs) corresponded closely to the time of peak increase in prolactin levels (3.0 +/- 1.1 hr). Abnormal behavioral responders had statistically significant greater increases in prolactin 1 to 4 hr after fenfluramine when compared to normal responders. Patients who developed an abnormal psychopathologic response to fenfluramine were characterized by higher levels of anxiety and agitation at the time of admission to the hospital but otherwise were not distinguishable on the basis of severity of other psychiatric symptoms. This study suggests that increased serotonergic transmission may trigger anxiety, psychosis, and mood elevation in specific vulnerable individuals, whereas other patients with similar psychiatric illnesses are not affected.     

Inhibitory effect of bifemelane on superoxide generation by activated neutrophils measured using a simple chemiluminescence method

We evaluated the effect of 4-(2-benzylphenoxy)-N-methylbutylamine hydrochloride (bifemelane hydrochloride) on superoxide production by human neutrophils using an MCLA-dependent chemiluminescence assay. Bifemelane hydrochloride dose-dependently inhibited superoxide production by neutrophils stimulated with phorbol myristate acetate, opsonized zymosan, or N-formyl-methionyl-leucyl-phenylalanine, while it had no effect on superoxide production by a hypoxanthine-xanthine oxidase system. These results indicate that bifemelane hydrochloride does not have a scavenging effect, but has an inhibitory effect on superoxide generation by neutrophils. Although this drug is commonly used for treating chronic cerebral infarction, it may also have a protective effect on acute ischemia/reperfusion injury.     

A prototype 3D optically interconnected neural network

We report the implementation of a prototype three-dimensional (3D) optoelectronic neural network that combines free-space optical interconnects with silicon-VLSI-based optoelectronic circuits. The prototype system consists of a 16-node input, 4-neuron hidden, and a single-neuron output layer, where the denser input-to-hidden-layer connections are optical. The input layer uses PLZT light modulators to generate optical outputs which are distributed over an optoelectronic neural network chip through space-invariant holographic optical interconnects. Optical interconnections provide negligible fan-out delay and allow compact, purely on-chip electronic H-tree type fan-in structure. The small prototype system achieves a measured 8-bit electronic fan-in precision and a calculated maximum speed of 640 million interconnections per second. The system was tested using synaptic weights learned off system and was shown to distinguish any vertical line from any horizontal one in an image of 4×4 pixels. New, more efficient light detector and small-area analog synapse circuits and denser optoelectronic neuron layouts are proposed to scale up the system. A high-speed, feed-forward optoelectronic synapse implementation density of up to 10⁴/cm² seems feasible using new synapse design. A scaling analysis of the system shows that the optically interconnected neural network implementation can provide higher fan-in speed and lower power consumption characteristics than a purely electronic, crossbar-based neural network implementation     

THE ELECTROIMPACT COMPACTION OIF POWDERS: MECHANICS, STRUCTURE AND PROPERTIES

An electroimpact compaction method recently developed for powder consolidation is described In terms of the basic principles of electric discharge and dynamic compaction processes. The influence of processing parameters, microstructural characteristics and mechanical properties of preforms obtained are discussed. Mathematical models for the mechanics of compaction, electrical resistance, discharge current variations and comparisons with experimental results are presented. The best set of properties are obtained when electrical discharge is applied to cause interparticle fusion at the instant when dynamic compaction pressure attains its peak level.     

Numerical models of creep and boundary sliding mechanisms in single-phase, dual-phase, and fully lamellar titanium aluminide

Finite element simulations of the high-temperature behavior of single-phase γ, dual-phase α₂+γ, and fully lamellar (FL) α₂+γTiAl intermetallic alloy microstructures have been performed. Nonlinear viscous primary creep deformation is modeled in each phase based on published creep data. Models were also developed that incorporate grain boundary and lath boundary sliding in addition to the dislocation creep flow within each phase. Overall strain rates are compared to gain an understanding of the relative influence each of these localized deformation mechanisms has on the creep strength of the microstructures considered. Facet stress enhancement factors were also determined for the transverse grain facets in each model to examine the relative susceptibility to creep damage. The results indicate that a mechanism for unrestricted sliding of γ lath boundaries theorized by Hazzledine and co-workers leads to unrealistically high strain rates. However, the results also suggest that the greater creep strength observed experimentally for the lamellar microstructure is primarily due to inhibited former grain boundary sliding (GBS) in this microstructure compared to relatively unimpeded GBS in the equiaxed microstructures. The serrated nature of the former grain boundaries generally observed for lamellar TiAl alloys is consistent with this finding.