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     

Pocket pagers in lots of one CIM

The Fusion program, a method for agile, flexible computer integrated manufacturing (CIM) at Motorola's Paging Products Group, is discussed. Fusion's CIM and automated assembly system can manufacture a wide variety of different products on the same production line. The development of the Fusion program and how it differs from its predecessor, the Bandit program, are described     

Proceedings of the Joint US/EU Workshop: urinary biomarkers to detect significant effects of environmental and occupational exposure to nephrotoxins

Tear cytokines and growth factors are likely to modulate the wound healing process following corneal epithelial injury. Hepatocyte growth factor (HGF) is a paracrine mediator of epithelial proliferation, motility, and differentiation that is produced by keratocytes and the lacrimal gland. Tear samples were collected preoperatively and one, two, and seven days postoperatively in eyes undergoing excimer laser surface ablation [photorefractive keratoplasty (PRK) or phototherapeutic keratoplasty (PTK)]. Tear HGF concentration was measured with a sensitive ELISA assay. Tear HGF production was calculated using the tear flow rate in the collection capillary and HGF concentration. Although the instantaneous concentration of HGF in tears decreased significantly in the days following PRK, a large increase in tear flow resulted in a marked increase in HGF bioavailability. The heparin-binding characteristics of HGF would result in increased binding to glycosaminoglycans and other heparin-like matrix components and, therefore, increased growth factor availability to the cognate recptor. This is the first report documenting changes in tear film HGF production. HGF may have an important function in maintenance and wound healing of the ocular surface epithelium since HGF is present in the normal tear film and the HGF secretion rate increases markedly in parallel with aqueous tear production following corneal surgical injury.     

Multi-emitter Si/GexSi1-x heterojunctionbipolar transistor with no base contact and enhanced logic functionality

We demonstrate multi-emitter Si/Ge_xSi_1-x n-p-n heterojunction bipolar transistors (HBT's) which require no base contact for transistor operation. The base current is supplied by the additional emitter contact under reverse bias due to the heavy doping of the emitter-base junction. Large-area HBT test structures exhibit good transistor characteristics, with current gain β≈400 regardless of whether the base current is supplied by a test base electrode or one of the emitter contacts. These devices have enhanced logic functionality because of emitter contact symmetry. Since device fabrication does not require base electrode formation, the number of processing steps can be reduced without significant penalty to HBT performance     

Comparison of the biodistribution and the efficacy of monoclonal antibody 323/A3 labeled with either 131I or 186Re in human ovarian cancer xenografts

The effects of arginine vasopressin (AVP) and oxytocin (OT) upon thyroid-stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) release were studied in euthyroid rats. Intracerebroventricular (i.c.v.) infusion of AVP in doses of 0.5 ng or 5 ng led to significant increases in plasma levels of TSH as well as FT4 and FT3. The effects of OT injected i.c.v. in similar doses were not consistent (there was no parallel between the changes of respective hormones plasma levels). It may be concluded that vasopressin modulate the pituitary-thyroid system function; AVP is probably a physiological stimulator of TSH and thyroid hormones secretion.     

Two distinct protein-protein interactions between the NIT2 and NMR regulatory proteins are required to establish nitrogen metabolite repression in Neurospora crassa

Unrecognized and untreated depression occurs frequently in Alzheimer's disease (AD) patients, adding to the agony already experienced by patient and caregiver. The authors screened AD patients living with a family caregiver for depression. Twelve patients with confirmed depression were treated in an open-label study with antidepressant medication, with dosage adjustment by a psychiatrist at Weeks 2, 4, 8, and 16. Data collection occurred at baseline, Week 4, and Week 16. Depression decreased significantly (p < .01). Contrary to expectations, patient functional capacity declined (p = .045). Cognition remained unchanged (p > .05). Caregiver burden, caregiver depressive symptomatology, and quality of life of patient and caregiver remained unchanged (p > .05). The authors conclude that depression in AD can be detected if a collateral source, such as the caregiver, is available. The depression can and should be treated. More research is needed to determine the impact on patient functioning, caregiver burden, caregiver depressive symptomatology, and quality of life of patient and caregiver.     

Solution structure of a DNA duplex containing the exocyclic lesion 3,N4-etheno-2'-deoxycytidine opposite 2'-deoxyguanosine

Vinyl chloride reacts with cellular DNA producing 3,N4-etheno-2'-deoxycytidine (epsilonC) along with other exocyclic adducts. The solution structure of an oligodeoxynucleotide duplex containing an epsilonC.dG base pair was determined by high-resolution NMR spectroscopy and molecular dynamics simulations. NMR data indicated that the duplex adopts a right-handed helical structure having all residues in anti orientation around the glycosylic torsion angle. The epsilonC adduct has a sugar pucker in the C3'-endo/C4'-exo region while the rest of the residues are in the C2'-endo/C3'-exo range. NOE interactions established Watson-Crick alignments for canonical base pairs of the duplex. The imino proton of the lesion-containing base pair resonated as a sharp signal that was resistant to water exchange, suggesting hydrogen bonding. Restrained molecular dynamics simulations generated three-dimensional models in excellent agreement with the spectroscopic data. The refined structures are slightly bent at the lesion site without major perturbations of the sugar-phosphate backbone. The adduct is displaced and shifted toward the major groove of the helix while its partner on the complementary strand remains stacked. The epsilonC(anti).dG(anti) base pair alignment is sheared and stabilized by the formation of hydrogen bonds. The biological implications of structures of epsilonC-containing DNA duplexes are discussed.     

How the Listeria monocytogenes ActA protein converts actin polymerization into a motile force

The ActA protein is an essential determinant of pathogenicity that is responsible for the actin-based motility of Listeria monocytogenes in mammalian cells and cell-free extracts. ActA appears to control at least four functions that collectively lead to actin-based motility: (1) initiation of actin polymerization, (2) polarization of ActA function, (3) transformation of actin polymerization into a motile force and (4) acceleration of movement mediated by the host protein profilin.     

Micropipelined asynchronous discrete cosine transform (DCT/IDCT)processor

We describe the design and implementation of an asynchronous discrete cosine transform/inverse discrete cosine transform (DCT/IDCT) processor core compliant with the CCITT recommendation H.261. First, a micropipelined implementation with level-sensitive latches is shown. This is improved by replacing the level-sensitive latches with dual-edge triggered flip-flops to save power and using completion-detection adders in the critical stage of the pipeline to exploit the data-dependent processing delay. Gate-level simulation of extracted layouts indicates that the performance of asynchronous implementations is comparable with that of a synchronous implementation based on an identical architecture. This is because part of the penalty introduced by handshaking circuitry in an asynchronous pipeline can be recovered by exploiting data-dependent processing delays with completion-detection circuitry. In pipelines with significant arithmetic processing such as the DCT/IDCT processor, this is easily accomplished. Our results are encouraging because asynchronous designs do not employ global clocking. In the near future when clock generation, clock distribution, and the power consumed in the clock circuitry become limiting factors in the design of large synchronous application specific integrated circuits (ASICs), asynchronous implementation methodology could be pursued as a real alternative