297 research outputs found
Oscillator neural network model with distributed native frequencies
We study associative memory of an oscillator neural network with distributed
native frequencies. The model is based on the use of the Hebb learning rule
with random patterns (), and the distribution function of
native frequencies is assumed to be symmetric with respect to its average.
Although the system with an extensive number of stored patterns is not allowed
to get entirely synchronized, long time behaviors of the macroscopic order
parameters describing partial synchronization phenomena can be obtained by
discarding the contribution from the desynchronized part of the system. The
oscillator network is shown to work as associative memory accompanied by
synchronized oscillations. A phase diagram representing properties of memory
retrieval is presented in terms of the parameters characterizing the native
frequency distribution. Our analytical calculations based on the
self-consistent signal-to-noise analysis are shown to be in excellent agreement
with numerical simulations, confirming the validity of our theoretical
treatment.Comment: 9 pages, revtex, 6 postscript figures, to be published in J. Phys.
Linear stability analysis of retrieval state in associative memory neural networks of spiking neurons
We study associative memory neural networks of the Hodgkin-Huxley type of
spiking neurons in which multiple periodic spatio-temporal patterns of spike
timing are memorized as limit-cycle-type attractors. In encoding the
spatio-temporal patterns, we assume the spike-timing-dependent synaptic
plasticity with the asymmetric time window. Analysis for periodic solution of
retrieval state reveals that if the area of the negative part of the time
window is equivalent to the positive part, then crosstalk among encoded
patterns vanishes. Phase transition due to the loss of the stability of
periodic solution is observed when we assume fast alpha-function for direct
interaction among neurons. In order to evaluate the critical point of this
phase transition, we employ Floquet theory in which the stability problem of
the infinite number of spiking neurons interacting with alpha-function is
reduced into the eigenvalue problem with the finite size of matrix. Numerical
integration of the single-body dynamics yields the explicit value of the
matrix, which enables us to determine the critical point of the phase
transition with a high degree of precision.Comment: Accepted for publication in Phys. Rev.
Nucleic acid-based fluorescent probes and their analytical potential
It is well known that nucleic acids play an essential role in living organisms because they store and transmit genetic information and use that information to direct the synthesis of proteins. However, less is known about the ability of nucleic acids to bind specific ligands and the application of oligonucleotides as molecular probes or biosensors. Oligonucleotide probes are single-stranded nucleic acid fragments that can be tailored to have high specificity and affinity for different targets including nucleic acids, proteins, small molecules, and ions. One can divide oligonucleotide-based probes into two main categories: hybridization probes that are based on the formation of complementary base-pairs, and aptamer probes that exploit selective recognition of nonnucleic acid analytes and may be compared with immunosensors. Design and construction of hybridization and aptamer probes are similar. Typically, oligonucleotide (DNA, RNA) with predefined base sequence and length is modified by covalent attachment of reporter groups (one or more fluorophores in fluorescence-based probes). The fluorescent labels act as transducers that transform biorecognition (hybridization, ligand binding) into a fluorescence signal. Fluorescent labels have several advantages, for example high sensitivity and multiple transduction approaches (fluorescence quenching or enhancement, fluorescence anisotropy, fluorescence lifetime, fluorescence resonance energy transfer (FRET), and excimer-monomer light switching). These multiple signaling options combined with the design flexibility of the recognition element (DNA, RNA, PNA, LNA) and various labeling strategies contribute to development of numerous selective and sensitive bioassays. This review covers fundamentals of the design and engineering of oligonucleotide probes, describes typical construction approaches, and discusses examples of probes used both in hybridization studies and in aptamer-based assays
The spike-timing-dependent learning rule to encode spatiotemporal patterns in a network of spiking neurons
We study associative memory neural networks based on the Hodgkin-Huxley type
of spiking neurons. We introduce the spike-timing-dependent learning rule, in
which the time window with the negative part as well as the positive part is
used to describe the biologically plausible synaptic plasticity. The learning
rule is applied to encode a number of periodical spatiotemporal patterns, which
are successfully reproduced in the periodical firing pattern of spiking neurons
in the process of memory retrieval. The global inhibition is incorporated into
the model so as to induce the gamma oscillation. The occurrence of gamma
oscillation turns out to give appropriate spike timings for memory retrieval of
discrete type of spatiotemporal pattern. The theoretical analysis to elucidate
the stationary properties of perfect retrieval state is conducted in the limit
of an infinite number of neurons and shows the good agreement with the result
of numerical simulations. The result of this analysis indicates that the
presence of the negative and positive parts in the form of the time window
contributes to reduce the size of crosstalk term, implying that the time window
with the negative and positive parts is suitable to encode a number of
spatiotemporal patterns. We draw some phase diagrams, in which we find various
types of phase transitions with change of the intensity of global inhibition.Comment: Accepted for publication in Physical Review
Prognostic impact of FAS/CD95/APO-1 in urothelial cancers: decreased expression of Fas is associated with disease progression
The death receptor Fas (Apo1/CD95) and Fas ligand (FasL) system is recognised as a major pathway for the induction of apoptosis in vivo, and antiapoptosis via its blockade plays a critical role in carcinogenesis and progression in several malignancies. However, the function of Fas–FasL system in urothelial cancer (UC) has not been elucidated. We therefore investigated the expression of Fas, FasL and Decoy receptor 3 for FasL (DcR3) in UC specimens and cell lines, and examined the cytotoxic effect of an anti-Fas-activating monoclonal antibody (mAb) in vitro. Immunohistochemical examinations of Fas-related molecules were performed on 123 UC and 30 normal urothelium surgical specimens. Normal urothelium showed Fas staining in the cell membrane and cytoplasm. In UC, less frequent Fas expression was significantly associated with a higher pathological grade (P<0.0001), a more advanced stage (P=0.023) and poorer prognosis (P=0.010). Fas and the absence thereof were suggested to be crucial factors with which to select patients requiring more aggressive treatment. Moreover, low-dose anti-Fas-activating mAb sensitised resistant cells to adriamycin, and this synergistic effect could be applied in the development of new treatment strategy for UC patients with multidrug-resistant tumours
Adenomatous Polyposis Coli Regulates Axon Arborization and Cytoskeleton Organization via Its N-Terminus
Conditional deletion of APC leads to marked disruption of cortical development and to excessive axonal branching of cortical neurons. However, little is known about the cell biological basis of this neuronal morphological regulation. Here we show that APC deficient cortical neuronal growth cones exhibit marked disruption of both microtubule and actin cytoskeleton. Functional analysis of the different APC domains revealed that axonal branches do not result from stabilized β-catenin, and that the C-terminus of APC containing microtubule regulatory domains only partially rescues the branching phenotype. Surprisingly, the N-terminus of APC containing the oligomerization domain and the armadillo repeats completely rescues the branching and cytoskeletal abnormalities. Our data indicate that APC is required for appropriate axon morphological development and that the N-terminus of APC is important for regulation of the neuronal cytoskeleton
Deletion of the Pichia pastoris KU70 Homologue Facilitates Platform Strain Generation for Gene Expression and Synthetic Biology
Targeted gene replacement to generate knock-outs and knock-ins is a commonly used method to study the function of unknown genes. In the methylotrophic yeast Pichia pastoris, the importance of specific gene targeting has increased since the genome sequencing projects of the most commonly used strains have been accomplished, but rapid progress in the field has been impeded by inefficient mechanisms for accurate integration. To improve gene targeting efficiency in P. pastoris, we identified and deleted the P. pastoris KU70 homologue. We observed a substantial increase in the targeting efficiency using the two commonly known and used integration loci HIS4 and ADE1, reaching over 90% targeting efficiencies with only 250-bp flanking homologous DNA. Although the ku70 deletion strain was noted to be more sensitive to UV rays than the corresponding wild-type strain, no lethality, severe growth retardation or loss of gene copy numbers could be detected during repetitive rounds of cultivation and induction of heterologous protein production. Furthermore, we demonstrated the use of the ku70 deletion strain for fast and simple screening of genes in the search of new auxotrophic markers by targeting dihydroxyacetone synthase and glycerol kinase genes. Precise knock-out strains for the well-known P. pastoris AOX1, ARG4 and HIS4 genes and a whole series of expression vectors were generated based on the wild-type platform strain, providing a broad spectrum of precise tools for both intracellular and secreted production of heterologous proteins utilizing various selection markers and integration strategies for targeted or random integration of single and multiple genes. The simplicity of targeted integration in the ku70 deletion strain will further support protein production strain generation and synthetic biology using P. pastoris strains as platform hosts
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