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PubMed2006

Recurrent neural network architecture with pre-synaptic inhibition for incremental learning.

We propose a recurrent neural network architecture that is capable of incremental learning and test the performance of the network. In incremental learning, the consistency between the existing internal representation and a new sequence is unknown, so it is not appropriate to overwrite the existing internal representation on each new sequence. In the proposed model, the parallel pathways from input to output are preserved as possible, and the pathway which has emitted the wrong output is inhibited by the previously fired pathway. Accordingly, the network begins to try other pathways ad hoc. This modeling approach is based on the concept of the parallel pathways from input to output, instead of the view of the brain as the integration of the state spaces. We discuss the extension of this approach to building a model of the higher functions such as decision making.

Affect↗
PubMed2001

Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.

To accumulate information on the coding sequences of unidentified genes, we have carried out a sequencing project of human cDNA clones which encode large proteins. We herein present the entire sequences of 100 cDNA clones of unidentified human genes, named KIAA1776 and KIAA1780-KIAA1878, from size-fractionated cDNA libraries derived from human fetal brain, adult whole brain, hippocampus and amygdala. Most of the cDNA clones to be entirely sequenced were selected as cDNAs which were shown to have coding potentiality by in vitro transcription/translation experiments, and some clones were chosen by using computer-assisted analysis of terminal sequences of cDNAs. Three of these clones (fibrillin2/KIAA1776, MEGF10/KIAA1780 and MEGF11/KIAA1781) were isolated as genes encoding proteins with multiple EGF-like domains by motif-trap screening. The average sizes of the inserts and corresponding open reading frames of eDNA clones analyzed here reached 4.7 kb and 2.4 kb (785 amino acid residues), respectively. From the results of homology and motif searches against the public databases, the functional categories of the predicted gene products of 54 genes were determined; 93% of these predicted gene products (50 gene products) were classified as proteins related to cell signaling/communication, nucleic acid management, or cell structure/motility. To collect additional information on these genes, their expression profiles were also studied in 10 human tissues, 8 brain regions, spinal cord, fetal brain and fetal liver by reverse transcription-coupled polymerase chain reaction, products of which were quantified by enzyme-linked immunosorbent assay.

Adult↗
PubMed2001

Prediction of the coding sequences of unidentified human genes. XXI. The complete sequences of 60 new cDNA clones from brain which code for large proteins.

As an extension of a sequencing project of human cDNA clones which encode large proteins of unidentified genes, we herein present the entire sequences of 60 cDNA clones for the genes named KIAA1879-KIAA1938. The cDNA clones were isolated from size-fractionated cDNA libraries derived from human fetal brain, adult whole brain and amygdala, and their protein-coding sequences were predicted. Thirty-seven cDNA clones entirely sequenced in this study were selected as cDNAs which have coding potentiality by in vitro transcription/translation experiments, and the remaining 23 cDNA clones were chosen by computer-assisted analysis of terminal sequences of cDNAs. The average sizes of the inserts and corresponding open reading frames of cDNA clones analyzed here were 4.5 kb and 2.2 kb (733 amino acid residues), respectively. Sequence analyses against the public databases enabled us to annotate the functions of the predicted products of the 25 genes; 84% of these predicted gene products (21 gene products) were classified into proteins related to cell signaling/communication, nucleic acid management, and cell structure/motility. In addition to the sequence information about these 60 genes, their expression profiles were also studied in some human tissues including brain regions by reverse transcription-coupled polymerase chain reaction, products of which were quantified by enzyme-linked immunosorbent assay.

Adult↗
PubMed1997

Power flow in the equine forelimb.

A method is described for the estimation of segmental powers and power flow during the stance phase in the equine forelimb, to demonstrate the sources and paths of energy flow through the limb segments. S-VHS video and force platform data were collected for 5 walking trials in a sound Dutch Warmblood horse. Two camera views were combined using direct linear transformation and the resultant sagittal plane positional and angular data used together with the vertical and cranio-caudal ground reaction forces to calculate moments about the ends of the 4 lowermost segments of the forelimb, and the reaction forces at the segment ends. Power flows were calculated across the proximal and distal ends of each segment and total segmental power computed. During initial and terminal stance, power flowed into the cannon segment proximally, and out distally. For the rest of stance, the flow in the cannon was distal to proximal. At the pastern, power flowed in proximally during initial loading, and out distally. For most of the rest of stance, the pattern of flow was distal to proximal, except for terminal stance, when power flowed in through both ends. The largest effect at the hoof is a loss of energy in terminal stance as power flowed out proximally and into the pastern. The pastern appears to receive most of the energy during loading and pushoff and transfers this energy up the limb during midstance.

Animals↗
PubMed1994

Galanin receptor in plasma membrane of canine small intestinal circular muscle.

High-affinity binding sites for galanin were identified and characterized in plasma membrane of circular muscle from canine small intestine using 125I-radioiodinated synthetic porcine galanin. Scatchard analysis indicated a high-affinity binding site on plasma membrane with a dissociation constant (Kd) of 0.58 nM and a binding capacity of 389 fmol/mg. Unlabeled galanin or NH2-terminal galanin fragments competitively inhibited the binding of 125I-galanin in a concentration-dependent manner, whereas the COOH-terminal fragment was inactive. Computer analysis of competitive binding data suggested a two-site model with a high-affinity (inhibitor constant, Ki = 0.01 nM) and a low-affinity (Ki = 2.8 nM) binding site. Guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) enhanced the dissociation of bound 125I-galanin. Cholera toxin (CTX) and GTP gamma S abolished the activity of the high-affinity binding site, leaving the low-affinity binding site. We conclude that galanin may act as an neurotransmitter to inhibit canine small intestinal smooth muscle contraction by interaction with a CTX-sensitive G protein-coupled specific receptor on muscle membrane. This receptor showed different G protein coupling from a synaptosomal receptor previously described in the same tissue preparations.

Animals↗
PubMed1991

Synchronized oscillatory activity in leech neurons induced by calcium channel blockers.

1. Leech ganglia were superfused with salines in which Ca2+ was replaced with equimolar concentrations of Co2+, Ni2+, or Mn2+. These salines elicited rhythmic membrane potential oscillations with cycle periods ranging from 8 to 25 s in all neurons examined within the ventral nerve cord. 2. Rhythmic activity consisted of a rapid depolarization to a prolonged (3-6 s) plateau level, followed by a rapid repolarization. Each depolarization elicited a burst of action potentials. Peak-to-trough amplitudes of the plateau depolarizations were up to 40 mV in some cells. The plateau depolarizations were separated by slowly depolarizing ramp potentials. 3. Oscillations in all neurons were synchronized (in phase) both within individual ganglia and between ganglia linked by connective nerves. Rhythmic activity in isolated ganglia persisted after the interposed connective nerves were cut. 4. The occurrence of oscillatory activity was strongly correlated with the block of chemical synaptic transmission. 5. Electrotonic interactions persisted during oscillatory activity and may be one mechanism by which oscillations are synchronized. 6. The phase of rhythmic impulse bursts monitored with extracellular electrodes could be reset by electrical stimulation of connective nerves but not by injection of current pulses into individual neurons. Phase reset appeared to occur within one cycle and to a fixed phase point (plateau termination). 7. Oscillatory activity was eliminated by 75-100% reductions of [Na+]o (Na+ replaced with N-methyl-D-glucamine). Smaller reductions of Na+ (by 25-50%) increased the cycle period of oscillations. 8. The Na(+)-K+ pump inhibitors ouabain and strophanthidin disrupted oscillations. Cells were depolarized by approximately 20 mV and fired tonically. After the initial washout of the inhibitors, cells repolarized and became quiescent. After several minutes of continued washing, oscillatory activity resumed. 9. A conceptual model is proposed to explain the mechanisms underlying oscillatory activity induced by Ca2+ channel blockers. According to this model, depolarizing plateaus are generated by a noninactivating Na+ conductance. Na+ influx during the plateau leads to an increase in [Na+]i, which activates an electrogenic Na(+)-K+ pump that contributes to plateau termination. 10. A quantitative computer simulation incorporating six types of currents (capacity, outward rectifying potassium, inward rectifying potassium, sodium, leakage, and an electrogenic sodium pump) demonstrates the plausibility of the conceptual model. 11. These data suggest that a novel Na(+)-based mechanism for membrane potential oscillation is revealed by blockade of Ca2+ channels in leech ganglia.

Animals↗
PubMed1996

Neuronal-based synaptic compensation: a computational study in Alzheimer's disease.

In the framework of an associative memory model, we study the interplay between synaptic deletion and compensation, and memory deterioration, a clinical hallmark of Alzheimer's disease. Our study is motivated by experimental evidence that there are regulatory mechanisms that take part in the homeostasis of neuronal activity and act on the neuronal level. We show that following synaptic deletion, synaptic compensation can be carried out efficiently by a local, dynamic mechanism, where each neuron maintains the profile of its incoming post-synaptic current. Our results open up the possibility that the primary factor in the pathogenesis of cognitive deficiencies in Alzheimer's disease (AD) is the failure of local neuronal regulatory mechanisms. Allowing for neuronal death, we observe two pathological routes in AD, leading to different correlations between the levels of structural damage and functional decline.

Alzheimer Disease↗
PubMed1996

Spike train processing by a silicon neuromorph: the role of sublinear summation in dendrites.

A dendritic tree, as part of a silicon neuromorph, was modeled in VLSI as a multibranched, passive cable structure with multiple synaptic sites that either depolarize or hyperpolarize local "membrane patches," thereby raising or lowering the probability of spike generation of an integrate-and-fire "soma." As expected from previous theoretical analyses, contemporaneous synaptic activation at widely separated sites on the artificial tree resulted in near-linear summation, as did neighboring excitatory and inhibitory activations. Activation of synapses of the same type close in time and space produced local saturation of potential, resulting in spike train processing capabilities not possible with linear summation alone. The resulting sublinear synaptic summation, as well as being physiologically plausible, is sufficient for a variety of spike train processing functions. With the appropriate arrangement of synaptic inputs on its dendritic tree, a neuromorph was shown to discriminate input pulse intervals and patterns, pulse train frequencies, and detect correlation between input trains.

Dendrites↗
PubMed1997

Remote, mobile telemedicine: the satellite transmission of medical data from Mount Logan.

The purpose of this investigation was to demonstrate the potential of remote, mobile telemedicine during a four-week, high-altitude mountaineering expedition to Mount Logan, Canada's highest summit. Using a mobile satellite terminal and a laptop computer (both powered by a photovoltaic solar panel), ECG tracings and blood pressure measurements, in addition to colour images, short-segment video and audio clips were transmitted during the course of the ascent. The data were transmitted via a mobile communications satellite to a ground station in Ottawa, a distance of over 4000 km. The data were then transferred to the public switched data network and delivered to the University of Ottawa Heart Institute for analysis. Similarly, data were transmitted from the ground station to the expedition team on Mount Logan throughout the ascent. Using this technique, medical diagnosis and emergency care can be facilitated in extreme and isolated locations lacking a telecommunications infrastructure. Such technology has applications in developing countries, disaster response efforts, remote civilian and military operations, and in space operations.

Canada↗
PubMed1999

Telemedicine in neurosurgery using international digital telephone services between Japan and Malaysia--technical note.

A new image transmission and teleconference system using international digital telephone services was established between Japan and Malaysia. This new system consists of an ordinary personal computer, image scanner, and terminal adapter for digital telephone lines. The quality of images transferred using this system was high enough for diagnosis and discussion except for images such as radiographs requiring huge data transfer. Transmission of one image took approximately 20 seconds. The cost performance was almost equal to the conventional mailing system. The most remarkable advantage of this new system is the high quality of transferred images, the cost and time performance, and security of the medical information. New communication systems using international digital networks including the internet may allow re-distribution of medical resources between advanced countries and developing countries in neurosurgery.

Academic Medical Centers↗
PubMed1977

On-line computerized data handling system for treating patients with renal disease.

Some patients with renal disease accrue 6,000 to 8,000 individual data items relating to symptoms, signs, laboratory information, and treatment in one year. To deal with the problem of handling so many data items, the following steps were taken: (1) a dictionary of terms peculiar to nephrology was created; (2) manual time-oriented records for nephrology were constructed; and (3) an on-line data processing system, using a PDP-11/70 computer and remote teleprocessing terminal, was developed. On the terminal screen, up to 11 consecutive patient visits can be displayed horizontally, with 18 data items displayed vertically. Up to 30 of the most recent patient visits are easily accessible. For patient treatment, a special feature allows a rearrangement and instantaneous display of any combination of data, thus permitting review of essential feedback relationships between clinical events and treatment.

Data Display↗
PubMed1987

Purification of protease nexin II from human fibroblasts.

Normal human fibroblasts secrete a protein named protease nexin II (PN II) which previously was shown to form sodium dodecyl sulfate (SDS)-stable complexes with epidermal growth factor-binding protein (EGF-BP). These complexes then bind to the same cells and are rapidly internalized and degraded (Knauer, D.J., and Cunningham, D.D. (1982) Proc. Natl. Acad. Sci. U.S.A. 79, 2310-2314). Here we describe a procedure for purifying PN II to apparent homogeneity from serum-free culture medium conditioned by human fibroblasts. The first step employed dextran sulfate-Sepharose affinity chromatography. Further purification was achieved by ion-exchange chromatography on DEAE-Sepharose followed by gel filtration on Sephacryl S-400. Sequence analysis of purified PN II identified 33 amino-terminal amino acids; a computer search of several protein sequence data banks failed to reveal homologies with other reported amino acid sequences. Purified PN II had an apparent Mr of 106,000 and an isoelectric point of approximately 7.2. It retained full activity after incubation in the presence of 0.05% SDS or at a pH of 1.5. PN II formed SDS-stable complexes with EGF-BP, the gamma subunit of 7 S nerve growth factor, and trypsin with estimated Mr of 120,000, 120,000, and 110,000, respectively. PN II was metabolically labeled with [35S]methionine and purified; the metabolically labeled protein formed complexes with EGF-BP. Complexes between purified PN II and EGF-BP bound to human fibroblasts. These results show that the purified protein possesses the properties previously attributed to PN II in cell culture medium.

Amino Acid Sequence↗
PubMed1983

Intraspinal metastasis of neuroblastoma--report of a case detected at autopsy.

Metastasis to the brain or spinal cord parenchyma is extremely rare in cases of neuroblastoma. We present a 3-year-7-month-old boy with neuroblastoma, stage IV, with intraspinal metastasis. He had no neurologic manifestation except incontinentia urinae and ataxia at the terminal stage. His cranial computed tomography scan showed high density areas in both cerebellar hemispheres which seemed to be distant metastatic masses. At autopsy, the metastases in the cerebellum were found to be due to dural infiltration but in the spinal cord parenchyma of the lumbar spine metastases were detected macroscopically. There were multiple distant metastatic areas near the roots, anterior and posterior. The neuroblastoma seemed to have spread along the roots by direct invasion from the meninges. In the future, the number of patients with metastasis into the brain or spinal cord parenchyma will increase because patients with progressive disease could live for a long time as a result of intensive chemotherapy. Observation of these cases will be helpful to clarify the routes of metastasis to these areas.

Adrenal Gland Neoplasms↗
PubMed1996

Gamma oscillation by synaptic inhibition in a hippocampal interneuronal network model.

Fast neuronal oscillations (gamma, 20-80 Hz) have been observed in the neocortex and hippocampus during behavioral arousal. Using computer simulations, we investigated the hypothesis that such rhythmic activity can emerge in a random network of interconnected GABAergic fast-spiking interneurons. Specific conditions for the population synchronization, on properties of single cells and the circuit, were identified. These include the following: (1) that the amplitude of spike afterhyperpolarization be above the GABAA synaptic reversal potential; (2) that the ratio between the synaptic decay time constant and the oscillation period be sufficiently large; (3) that the effects of heterogeneities be modest because of a steep frequency-current relationship of fast-spiking neurons. Furthermore, using a population coherence measure, based on coincident firings of neural pairs, it is demonstrated that large-scale network synchronization requires a critical (minimal) average number of synaptic contacts per cell, which is not sensitive to the network size. By changing the GABAA synaptic maximal conductance, synaptic decay time constant, or the mean external excitatory drive to the network, the neuronal firing frequencies were gradually and monotonically varied. By contrast, the network synchronization was found to be high only within a frequency band coinciding with the gamma (20-80 Hz) range. We conclude that the GABAA synaptic transmission provides a suitable mechanism for synchronized gamma oscillations in a sparsely connected network of fast-spiking interneurons. In turn, the interneuronal network can presumably maintain subthreshold oscillations in principal cell populations and serve to synchronize discharges of spatially distributed neurons.

Animals↗
PubMed1992

[Comparative studies with quantitative computed tomography and dual-energy x-ray absorptiometry on bone density in renal osteopathy].

Measurements of bone density were carried out in 25 patients on dialysis for terminal renal insufficiency, using quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA). Unlike in subjects with normal kidneys, there was no significant correlation between these methods in this series. Ten patients showed an increase in bone density of the vertebral spongiosa on QCT measurements, which was interpreted as due to osteosclerotic bone changes in renal osteopathy. QCT showed advantages over DXA in demonstrating these changes.

Absorptiometry, Photon↗
PubMed1987

Differential effects of p-chlorophenylalanine on indoleamines in brainstem nuclei and spinal cord of rats. II. Identification of immunohistochemically stained structures using computer-assisted image enhancement techniques.

Following intraperitoneal injection of p-chlorophenylalanine (PCPA, 400 and 600 mg/kg) on 3 consecutive days, the brainstem and lumbar cord of rats were removed, frozen-sectioned and immunohistochemically stained (PAP method) for serotonin (5-HT). Using computer-assisted image analysis, the density of 5-HT staining in control, 400 and 600 mg/kg PCPA groups was determined. The mean number of pixels (representing 5-HT staining) was determined in 6 areas in the brainstem containing 5-HT cell bodies (nuclei raphe pallidus, raphe obscurus, rostral and caudal raphe magnus, raphe dorsalis and paragigantocellularis lateralis) and in the dorsal and ventral spinal cord. The results suggest a differential depletion of 5-HT within brainstem nuclei following PCPA treatment in that the most marked dose-related reductions were observed in nucleus raphe obscurus and caudal nucleus raphe magnus. Furthermore, a computer program designed to isolate terminal structures in the spinal cord identified a differential depletion of 5-HT terminals in the dorsal horn versus the ventral horn. The present study describes 3 analytical approaches combining immunohistochemistry with the computer-assisted image analysis technique and allows comparison between groups of animals which received the same or different drug treatments.

Animals↗
PubMed2001

Leaderless transcripts of the crenarchaeal hyperthermophile Pyrobaculum aerophilum.

We mapped transcription start sites for ten unrelated protein-encoding Pyrobaculum aerophilum genes by primer extension and S(1) nuclease mapping. All of the mapped transcripts start at the computationally predicted translation start codons, two of which were supported by N-terminal protein sequencing. A whole genome computational analysis of the regions from -50 to +50 nt around the predicted translation starts codons revealed a clear upstream pattern matching the consensus sequence of the archaeal TATA box located unusually close to the translation starts. For genes with the TATA boxes that best matched the consensus sequence, the distance between the TATA box and the translation start codon appears to be shorter than 30 nt. Two other promoter elements distinguished were also found unusually close to the translation start codons: a transcription initiator element with significant elevation of C and T frequencies at the -1 position and a BRE element with more frequent A bases at position -29 to -32 (counting from the translation start site). We also show that one of the mapped genes is transcribed as the first gene of an operon. For a set of genes likely to be internal in operons the upstream signal extracted by computer analysis was a Shine-Dalgarno pattern matching the complementary sequence of P. aerophilum 16 S rRNA. Together these results suggest that the translation of proteins encoded by single genes or genes that are first in operons in the hyperthermophilic crenarchaeon P. aerophilum proceeds mostly, if not exclusively, through leaderless transcripts. Internal genes in operons are likely to undergo translation via a mechanism that is facilitated by ribosome binding to the Shine-Dalgarno sequence.

5' Untranslated Regions↗
PubMed1993

Computer use in private dental practice in Australia, 1991.

There was a 70 per cent response to a mail questionnaire to a 1:3 sample of Australian Dental Association members in private practices (n = 1931). Computers were used by 37 per cent of practices. Main computer applications used were for: accounting (84%); patient billing (80%); word processing (79%); and patient recall (61%). External bureau services were used by 4 per cent of practices with most computers being in-house (single terminal 66%; multiple terminal 33%). The more dentists in a practice, the more likely was a computer to be used. Principal users were secretary/receptionists. Service and software were the most important factors in choice of computer system. Many practice computer users (67%) also had a Personal Computer at home compared with only 36 per cent of the non-users. Many respondents indicated the need for continuing education in computers (67% users; 61% non-users). More than half of the non-users indicated future use of computers for accounting, billing and recall. There has been a considerable increase in the use of computers in private practice (37%) since the Australian Dental Association Dental Practice Survey in 1983/84 (9%).

Age Factors↗