Use of artificial neural networks in modeling associations of discriminant factors: towards an intelligent selective breast cancer screening.

In order to improve the costs/benefits ratio of breast cancer (BC) screenings, the author evaluated the performance of a back-propagation artificial neural network (ANN) to predict an outcome (cancer/not cancer) to be used as classificator. Networks were trained on data from familial history of cancer, and sociodemographic, gynecoobstetric and dietary variables. The ANN achieved up to 94.04% of positive predictive value and 97.60% of negative predictive value. Results could operate as guidelines for preselecting women who would be considered as a BC high-risk subpopulation. The procedure--not only based on age factor, but on a multifactorial basis--appears to be a promising method of achieving a more efficient detection of preclinical, asymptomatic BC cases.     

Experimental Investigations of an Impairment in Phonological Encoding

The speech of a patient with a mild impairment in phonological encoding or Reproduction Conduction Aphasia was investigated using a series of specially designed experimental tasks The patient committed phonemic paraphasias in all speech production tasks although these were somewhat less pronounced in repetition than other single word tasks On a task requiring the recital of word strings e g dam sauce tide goat knock meat night make his performance was found to be sensitive to rate of speech and size of anticipated planning unit Like normal controls he showed a strong lexical outcome effect and his anticipations outnumbered perseverations However unlike normals he showed no sensitivity to the similarity of phonemes in the target string and errors peaked towards the ends of words rather than at their onsets Results are interpreted within an interactive activation framework Existing interactive accounts of aphasia are considered as well as some alternatives The implications of word position findings for accounts of serial order effects are also discussed     

Carcinogenesis--devolution towards an ancient nucleated pre-eukaryotic level

Because the mitochondria and the cells housing them are obligatory symbionts, the evolutionary history of cells forms the locus minoris resistentiae which is the prerequisite for the carcinogenetic process. During carcinogenesis, the cells devolve towards an ancient anaerobic nucleated pre-eukaryotic level. True carcinogens cause an accumulation of inclusion bodies in the inner, bacterial, mitochondrial membrane. The mitochondrial damage which is detectable only in the early pretumorous stages, results in the respiratory surface with its enzymes being specifically changed, the mitochondrial and nuclear cycles no longer coinciding, the energy generation being forced to reuse the latent, "prehistoric", mode of respiration and the mitochondrial enzyme systems of soil bacterial origin becoming adapted to use other and more versatile metabolic pathways with a wider variety of end-products than classical glycolysis which produces lactate only. Neither external carcinogens nor oncogens are necessary. An increased, prolonged cell replication activity of physiological type is sufficient to initiate and maintain the process in animals with an inherited neoplastic disposition located in the inner mitochondrial membrane. The neoplastic disposition is inherited maternally: in fertilization the ovum does not receive mitochondria from the spermatocyte. The final results are an overall retardation of cell processes and instability in its structural and functional repertoire, the cytoskeleton (differentiation organelle) of the malignant cell manifesting special patterns. The proposed devolutionary mechanism is feasible as DNA packages are physiological components of soil bacterial membrane and can remain dormant (repressed) for years, or for ever, but under suitable conditions can generate seemingly new species, and particularly because enzyme adaptability is the unique privilege of soil bacteria.     

Development of an artificial synapse using an electrochemical micropump

Improving the resolution of artificial sensory organs requires an interface that receives external information from electronic circuits and stimulates appropriate neurons individually in response to that information. The method of electric stimulation in available artificial sensory organs is fairly nonselective; therefore, we developed a method of chemical stimulation of neurons using a neurotransmitter containing an electrochemical micropump powered by the bubbling that occurs during water electrolysis. The micropump contains a glass nozzle with a tip 10µm in diameter. Two blackened platinum electrodes for the electrolysis were inserted into the body of the pump, which was filled with neurotransmitter solution. The distance between a neuron of the gastropod Aplysia and the tip of the nozzle was adjusted to about 100µm. A potential difference of 3.0V was applied to the electrodes to propel the solution toward the neuron while its membrane potential was monitored. Administration of 1-mM acetylcholine to a resting neuron caused neural firing only when the voltage was applied for 0.5s and without a time lag. During administration of 50-mM -aminobutyric acid to spontaneously firing neurons, the firing disappeared with a time lag of 1s after application of 3.0V. We concluded that an electrochemical micropump can be applied for rapid neurotransmitter administration to control the excitation and inhibition of neurons. This simple pump can be miniaturized to create synapses in artificial sensory organs.     

Controlled in vitro growth of cell microtubes: towards the realisation of artificial microvessels

The aim of this study is to realise in vitro microtubular structures for Tissue Engineering applications. The strategy adopted consists in the use of cylindrical polymeric scaffolds, on which connective tissue cells (murine fibroblasts) can adhere and proliferate. We supply stereotropic and chemical stimuli which induce the cells to cover the whole cylindrical structure and to produce an extra-cellular matrix (ECM) which acts as an adhesive for cell aggregation and assembly. Stereotropic stimuli were provided using purpose designed seeding and proliferation chambers whilst the addition of ascorbic acid to the culture medium furnished chemical stimuli. To obtain cylindrical cellular structures two approaches are considered: the first one consists in the use of biodegradable scaffolds, the second one consists in the use of non-biodegradable scaffolds which can subsequently be withdrawn. The results show that a 14-μm thick cell and ECM coating grows over nylon strands, and can also be coerced to form an effective connection system with external tubing.     

Rheological characterization of an artificial synovial fluid

Rheological measurements on two classes of artificial synovial fluids have been carried out in the attempt to get a suitable but cheap lubricant for wear tests of prosthetic materials. Fluids of both classes are solutions of hyaluronic acid (HA) that, for one class, is dissolved into a simple Ringer solution whereas, for the other class, into a mixture of human serum and Ringer solution. Similar rheological properties have been observed for both classes of fluids. Experimental results have been interpreted by two classical models that are commonly used in the literature to describe the rheological behavior of colloidal systems and of polymer solutions with high entanglement density, respectively. The quality of correlations shows that, at high HA concentrations, entangled structures are largely present and cannot be neglected.     

Requirements for an artificial intervertebral disc.

Intervertebral disc degeneration is an important social and economic problem. Presently available artificial intervertebral discs (AIDs) are insufficient and the main surgical intervention is still spinal fusion. The objective of the present study is to present a list of requirements for the development of an AID which could replace the human lumbar intervertebral disc and restore its function. The list addresses geometry, stiffness, range of motion, strength, facet joint function, center of rotation, fixation, failsafety and implantation technique. Date are obtained from the literature, quantified where possible and checked for consistency. Existing AIDs are evaluated according to the presented list of requirements. Endplate size is a weak point in existing AIDs. These should be large and fit vertebral bodies to prevent migration. Disc height and wedge angle should be restored, unless this would overstretch ligaments. Finally, stiffness and range of motion in all directions should equal those of the healthy disc, except for the axial rotation to relieve the facet joints.     

Evolving collective behavior in an artificial ecology

Collective behavior refers to coordinated group motion, common to many animals. The dynamics of a group can be seen as a distributed model, each "animal" applying the same rule set. This study investigates the use of evolved sensory controllers to produce schooling behavior. A set of artificial creatures "live" in an artificial world with hazards and food. Each creature has a simple artificial neural network brain that controls movement in different situations. A chromosome encodes the network structure and weights, which may be combined using artificial evolution with another chromosome, if a creature should choose to mate. Prey and predators coevolve without an explicit fitness function for schooling to produce sophisticated, nondeterministic, behavior. The work highlights the role of species' physiology in understanding behavior and the role of the environment in encouraging the development of sensory systems.     

Evolvable self-replicating molecules in an artificial chemistry

This paper gives details of Squirm3, a new artificial environment based on a simple physics and chemistry that supports self-replicating molecules somewhat similar to DNA. The self-replicators emerge spontaneously from a random soup given the right conditions. Interactions between the replicators can result in mutated versions that can outperform their parents. We show how artificial chemistries such as this one can be implemented as a cellular automaton. We concur with Dittrich, Ziegler, and Banzhaf that artificial chemistries are a good medium in which to study early evolution.     

Ischemic tolerance in the cochlea

Ischemic tolerance in the cochlea was investigated in a gerbil model of cochlear ischemia. Transient cochlear ischemia was produced by extracranial occlusion of the bilateral vertebral arteries. The gerbils were divided into two groups; single ischemia group and double ischemia group. In the single ischemia group, animals were subjected to lethal cochlear ischemia for 15 min. In the double ischemia group, animals were subjected to sublethal cochlear ischemia for 2 min at 2 days before lethal ischemia for 15 min. Consequently, sublethal ischemia prevented lethal ischemia-induced hair cell degeneration and ameliorated hearing impairment, suggesting ischemic tolerance in the cochlea.     

Ototoxicity: an argument for evaluation of the cochlea in safety testing in animals

The cochlea is one of the more common targets for toxic effects, yet current toxicologic screening in animals does not routinely evaluate the cochlea as a potential target organ. Although histopathologic sections are routinely taken from the eye and the optic nerve and tract and most studies include at least 1 section through the nasal cavity and olfactory mucosa, the cochlea is not histopathologically examined in routine toxicity studies. Unfortunately, routine clinical examinations frequently miss ototoxicity because rodents and other species can lose most of their high-frequency hearing and still respond to most ambient noises. Ototoxicity as a deficiency in toxicologic screening can be remedied by using well-established histopathologic and behavioral methods or electrophysiologic methods, such as brain stem auditory evoked responses (BAERs). Once the equipment is in place, BAERs can be obtained quickly and easily for ototoxicity screening (approximately 15 minutes for paired testing of 2 rats and 30 minutes each for dogs). BAERs also can be used in virtually all mammalian species. Three or 4 probe frequencies (eg, 4, 8, 16, and 32 kHz), representing different areas of the cochlea, can be tested in a few minutes with subcutaneous electrodes under short-acting chemorestraint. Given the availability of several approaches to screening for ototoxicity and the importance of the auditory function in human health, safety tests of chemicals and drugs should include an effective screening test for ototoxicity.