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BackgroundMicroRNA (miRNA) regulates cellular processes by acting on specific target genes, and cellular processes proceed through multiple interactions often organized into pathways among genes and gene products. Hundreds of miRNAs and their target genes have been identified, as are many miRNA-disease associations. These, together with huge amounts of data on gene annotation, biological pathways, and protein–protein interactions are available in public databases. Here, using such data we built a database and web service platform, miRNA disease regulatory network (miRDRN), for users to construct disease and tissue-specific miRNA-protein regulatory networks, with which they may explore disease related molecular and pathway associations, or find new ones, and possibly discover new modes of drug action.MethodsData on disease-miRNA association, miRNA-target association and validation, gene-tissue association, gene-tumor association, biological pathways, human protein interaction, gene ID, gene ontology, gene annotation, and product were collected from publicly available databases and integrated. A large set of miRNA target-specific regulatory sub-pathways (RSPs) having the form (T,G1,G2) was built from the integrated data and stored, whereTis a miRNA-associated target gene,G1(G2) is a gene/protein interacting withT(G1). Each sequence (T,G1,G2) was assigned ap-value weighted by the participation of the three genes in molecular interactions and reaction pathways.ResultsA web service platform, miRDRN (http://mirdrn.ncu.edu.tw/mirdrn/), was built. The database part of miRDRN currently stores 6,973,875p-valued RSPs associated with 116 diseases in 78 tissue types built from 207 diseases-associated miRNA regulating 389 genes. miRDRN also provides facilities for the user to construct disease and tissue-specific miRNA regulatory networks from RSPs it stores, and to download and/or visualize parts or all of the product. User may use miRDRN to explore a single disease, or a disease-pair to gain insights on comorbidity. As demonstrations, miRDRN was applied: to explore the single disease colorectal cancer (CRC), in which 26 novel potential CRC target genes were identified; to study the comorbidity of the disease-pair Alzheimer’s disease-Type 2 diabetes, in which 18 novel potential comorbid genes were identified; and, to explore possible causes that may shed light on recent failures of late-phase trials of anti-AD,BACE1inhibitor drugs, in which genes downstream toBACE1whose suppression may affect signal transduction were identified.

Objective The current therapeutic strategy for posttraumatic osteoarthritis (PTOA) focuses on early intervention to attenuate disease progression, preserve joint function, and defer joint replacement timing. Sequential transcriptomic changes of articular cartilage in a rat model were investigated to explore the molecular mechanism in early PTOA progression. Design Anterior cruciate ligament transection and medial meniscectomy (ACLT + MMx)–induced PTOA model was applied on male Wistar rats. Articular cartilages were harvested at time 0 (naïve), 2 week, and 4 weeks after surgery. Affymetrix Rat genome 230 2.0 array was utilized to analyze the gene expression changes of articular cartilages. Results We identified 849 differentially expressed genes (DEGs) at 2 weeks and 223 DEGs at 4 weeks post–ACLT + MMx surgery compared with time 0 (naïve group). Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to gain further insights from these DEGs. 22 novel genes and 1 novel KEGG pathway (axon guidance) in cartilage degeneration of osteoarthritis were identified. Axon guidance molecules— Gnai1, Sema4d, Plxnb1, and Srgap2 commonly dysregulated in PTOA progression. Gnai1 gene showed a concordant change in protein expression by immunohistochemistry staining. Conclusions Our study identified 22 novel dysregulated genes and axon guidance pathway associated with articular cartilage degeneration in PTOA progression. These findings provide the potential candidates of biomarkers and therapeutic targets for further investigation.

Supplemental material, Table_S5 for Transcriptome Analysis Reveals Novel Genes Associated with Cartilage Degeneration in Posttraumatic Osteoarthritis Progression by Chih-Chung Liu, Hoong-Chien Lee, Yi-Shian Peng, Ailun Heather Tseng, Jia-Lin Wu, Wei-Yuan Tsai, Chih-Shung Wong and Li-Jen Su in CARTILAGE

An interactive tool to visualize the K-string composition of long DNA sequences including bacterial complete genomes is described. It is especially useful for exploring short palindromic structures in the sequences. The SeeDNA program runs on Red Hat Linux with GTK+ support. It displays two-dimensional (2D) or one-dimensional (1D) histograms of the K-string distribution of a given sequence and/or its randomized counterpart. It is also capable of showing the difference of K-string distributions between two sequences. The C source code using the GTK+ package is freely available.

The fact that many chemotherapeutic drugs cause chemoresistance and side effects during the course of colorectal cancer treatment necessitates development of novel cytotoxic agents aiming to attenuate new molecular targets. Here, we show that Astragalus membranaceus (Fischer) Bge. var. mongolicus (Bge.) Hsiao (AM), a traditional Chinese medicine, can inhibit tumor growth in vivo and elucidate the underlying molecular mechanisms. The antitumor effect of AM was assessed on the subcutaneous tumors of human colorectal cancer cell line HCT116 grafted into nude mice. The mice were treated with either water or 500 mg/kg AM once per day, before being sacrificed for extraction of tumors, which were then subjected to microarray expression profiling. The gene expression of the extraction was then profiled using microarray analysis. The identified genes differentially expressed between treated mice and controls reveal that administration of AM suppresses chromosome organization, histone modification, and regulation of macromolecule metabolic process. A separate analysis focused on differentially expressed microRNAs revealing involvement of macromolecule metabolism, and intracellular transport, as well as several cancer signaling pathways. For validation, the input of the identified genes to The Library of Integrated Network-based Cellular Signatures led to many chemopreventive agents of natural origin that produce similar gene expression profiles to that of AM. The demonstrated effectiveness of AM suggests a potential therapeutic drug for colorectal cancer.

// Szu-Mam Liu 1 , Jean Lu 2 , Hoong-Chien Lee 1,3,4 , Feng-Hsiang Chung 1,3 and Nianhan Ma 1 1 Institute of Systems Biology and Bioinformatics, National Central University, Jhongli, Taiwan 2 Genomics Research Center, Academia Sinica, Taipei, Taiwan 3 Center for Dynamical Biomarkers and Translational Medicine, National Central University, Jhongli, Taiwan 4 Department of Physics, Chung Yuan Christian University, Jhongli, Taiwan Correspondence: Nianhan Ma, email: // Keywords : miR-524-5p, melanoma, BRAF, ERK2, MAPK signaling, microRNA Received : June 20, 2014 Accepted : September 08, 2014 Published : September 08, 2014 Abstract It has been well documented that miRNAs can modulate the effectiveness of cancer-associated signaling pathways. Mitogen-activated protein kinase (MAPK/ERK) signaling plays an essential role in the progression of many cancers, including melanoma and colon cancers. However, no single miRNA is reported to directly target multiple components of the MAPK/ERK pathway. We performed a miRNA PCR array screening with various MAPK/ERK signaling activities. The miRNA array data revealed that the expression of miR-524-5p was decreased in cells with an active MAPK/ERK pathway and confirmed that the expression of miR-524-5p is inversely associated with the activity of the MAPK/ERK pathway. We demonstrated that miR-524-5p directly binds to the 3’-untranslated regions of both BRAFandERK2 and suppresses the expression of these proteins. Because BRAF and ERK2 are the main components of MAPK signaling, the overexpression of miR-524-5p effectively inhibits MAPK/ERK signaling, tumor proliferation, and melanoma cell migration. Moreover, tumors overexpressing miR-524-5p were significantly smaller than those of the negative control mice. Our findings provide new insight into the role of miR-524-5p as an important miRNA that negatively regulates the MAPK/ERK signaling pathway, suggesting that miR-524-5p could be a potent therapeutic candidate for melanoma treatment.

Objectives: Although high abundant cystatin c (CysC) in cerebrospinal fluid (CSF) is well known, its ambiguous role associated with pain still remains unclear. This study evaluated the effects of intrathecal CysC content from chronic pain caused by osteoarthritis (OA) and the novel relationship with matrix metalloproteinases 2 and 9 (MMP2 and MMP9) in CSF. Methods: Samples of CSF were obtained from 8 elderly patients (65 y and above) with OA with lower limb pain for at least 6 months (OA group) and 8 sex-matched and age-matched relatively healthy elderly individuals without any pain problems (control group). The intrathecal CysC, MMP2, and MMP9 were examined by Western blotting. The analysis of CysC cleavage under different conditions was performed through silver staining and using massspectroscopy (SELDI-TOF) on 2 groups. Results: Expression of full-length CysC and pro-MMP2 proteins showed statistically significant upregulation (P = 0.0004 vs. 0.03), and expression of MMP9 protein showed downregulation (P = 0.007) in the OA group. Both MMP9 and MMP2 initiated the mechanism for full-length CysC cleavage only in the presence of CSF. However, MMP9 showed greater ability than MMP2 for CysC cleavage in control and OA groups in sliver staining. Incubation of CSF with the MMP9 inhibitor led to the suppression of CysC cleavage in SELDI-TOF. Discussion: These findings provide the first in vivo evidence on a relationship between CysC and gelatinases (MMP2 and MMP9), and could facilitate further investigation of novel interactions among these proteins within the proteomics field, especially protein-protein interactions involved in pain.

A systemic approach was used to identify the possible mechanisms underlying the development of 5-fluorouracil (5FU)-induced resistance on HCT116 colon cancer cells. From microarray analysis, HCT116 high-dose 5FU-resistant subclones showed differential gene expression compared to HCT116-sensitive clones. According to gene ontology, and Kyoto Encyclopedia of Genes and Genomes pathways, the up-regulated genes were related to cell death and lupus erythematosus, respectively. On the other hand, the down-regulated genes were related to cell division or DNA replication. Connectivity map (cMAP) analysis revealed that the molecular drugs, such as antiasthmatic or antiallergy agents that have negative correlations with cMAP score, may have beneficial effect for the resistant subclones. Our findings suggested that the feasibility of cMAP combining microarray gene expression profile may help identify a potential drug that possibly will reverse the effect of 5FU-induced resistance.

The study was to examine the effect of Hylan G-F 20 on the progression of posttraumatic osteoarthritis (PTOA) and the expression of the circadian genes neuronal PAS domain protein 2 (NPAS2) and period 2 (Per2).We used the anterior cruciate ligament transaction and medial menisectomy (ACLT+MMx) model in Wistar rats. The rats were divided into three groups, the sham-operated group, the Hylan G-F 20-treated group, and the saline-treated group. Rats which underwent ACLT + MMx surgery were injected intraarticularly with, respectively, Hylan G-F 20 or saline once a week for 3 consecutive weeks, starting 7days after surgery. The gross morphology and histopathology of the experimental knee joints were evaluated at the end of week 6. Expression of the NPAS2 and Per2 genes was measured by real-time PCR.Hylan G-F 20 suppressed the articular cartilage destruction and synovitis compared to the saline-treated group. Compared to the sham-operated group, the Hylan G-F 20-treated group showed significantly upregulated expression of NPAS2 in cartilage (2.53±0.08-fold higher; p

The Shannon information (SI) in distributions of occurrence frequency of short words in whole genomes is shown to exhibit universality. For given word length, the SI in genomes of all lengths is the same as that in random sequences of a universal lengths L r . For the shorter words L r is far shorter than the genome. For example, L r ∼ 1000 bases for three-letter words. We further show that whole genomes are highly self-similar in the sense that any segment of the genome down to a length of Λ sim , about twice L r , also shares the universal property. We devise a simple genome growth model in which genome-size sequences grown by maximally stochastic segmental duplication and random mutation possess the universal and self-similar properties of genomes.

The DNA of some naturally competent species of bacteria contains a large number of evenly distributed copies of a short sequence. This highly overrepresented sequence is believed to be an uptake signal sequence (USS) that helps bacteria to take up DNA selectively from (dead) members of their own species. For some time it has been assumed that the USS evolved in order to enable bacteria to distinguish between conspecific and nonconspecific DNA fragments (the preference-first hypothesis). Recently, Redfield suggested that this hypothesis is not in fact realistic, as it would require biologically implausible group selection. In this article we present a model designed to demonstrate the emergence of similar USSs in a population of simulated evolving agents. We use this model to examine the conditions under which a USS will emerge in a preference-first scenario.

Statistical analysis of frequency occurrence of short words in complete genomes reveals the existence of a set of universal lengths common to all extant complete microbial genomes. This phenomenon is consistent with a model for genome growth in which primitive genomes grew mainly by maximally stochastic duplications of short segments from an initial length of about 200 nucleotides. The relevance of these results to the so-called RNA world in which life began and evolved before the rise of proteins is discussed.

Analysis of the frequency of occurrence of short oligonucleotides in typical bacterial genomes reveals that they exhibit the statistical characteristics of a DNA sequence of a much shorter length. This peculiar property suggests a model for genome growth in which a genome evolves by random mutation but primarily grows by random segmental self-copying. Computer-generated genome sequence based on this model indeed has statistical properties similar to those of bacterial genomes.

// Ming-Hui Lee 1, * , Wan-Pei Su 1, * , Wan-Jen Wang 1, * , Sing-Ru Lin 1, * , Chen-Yu Lu 1, * , Yu-An Chen 1, * , Jean-Yun Chang 1 , Shenq-Shyang Huang 1 , Pei-Yi Chou 1 , Siou-Ru Ye 1 , Szu-Jung Chen 1 , Huan He 1 , Ting-Hsiu Liu 1 , Ying-Tsen Chou 2 , Li-Jin Hsu 3, 4, * , Feng-Jie Lai 5 , Shean-Jen Chen 6 , Hoong-Chien Lee 7 , David Kakhniashvili 8 , Steven R. Goodman 8 , Nan-Shan Chang 1, 2, 4, 6, 9 1 Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, ROC 2 Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan, Taiwan, ROC 3 Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University Medical College, Tainan, Taiwan, ROC 4 Center of Infectious Disease and Signal Research, National Cheng Kung University, Tainan, Taiwan, ROC 5 Department of Dermatology, Chi-Mei Medical Center, Tainan, Taiwan, ROC 6 Advanced Optoelectronic Technology Center, National Cheng Kung University Medical College, Tainan, Taiwan, ROC 7 Graduate Institute of Systems Biology and Bioinformatics, National Central University, Zhongli, Taiwan, ROC 8 Institute of Biomedical Sciences and Technology, Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY, USA 9 Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA * These authors have contributed equally to this work Correspondence to: Nan-Shan Chang, e-mail: nschang13827@gmail.com Keywords: Zfra, skin cancer, melanoma, metastasis, stemness Received: September 18, 2014 Accepted: December 11, 2014 Published: February 20, 2015 ABSTRACT Zfra is a 31-amino-acid zinc finger-like protein, which participates in the tumor necrosis factor signaling. Here, we determined that when nude mice and BALB/c mice were pre-injected with nanogram levels of a synthetic Zfra1–31 or truncated Zfra4–10 peptide via tail veins, these mice became resistant to the growth, metastasis and stemness of melanoma cells, and many malignant cancer cells. The synthetic peptides underwent self-polymerization in phosphate-buffered saline. Alteration of the Ser8 phosphorylation site to Gly8 abolished Zfra aggregation and its-mediated cancer suppression in vivo . Injected Zfra peptide autofluoresced due to polymerization and was trapped mainly in the spleen. Transfer of Zfra-stimulated spleen cells to naive mice conferred resistance to cancer growth. Zfra-binding cells, designated Hyal-2+ CD3- CD19- Z cells, are approximately 25–30% in the normal spleen, but are significantly downregulated (near 0–3%) in tumor-growing mice. Zfra prevented the loss of Z cells caused by tumors. In vitro stimulation or education of naive spleen cells with Zfra allowed generation of activated Z cells to confer a memory anticancer response in naive or cancer-growing mice. In particular, Z cells are abundant in nude and NOD-SCID mice, and can be readily activated by Zfra to mount against cancer growth.

Drug repurposing has become an increasingly attractive approach to drug development owing to the ever-growing cost of new drug discovery and frequent withdrawal of successful drugs caused by side effect issues. Here, we devised Functional Module Connectivity Map (FMCM) for the discovery of repurposed drug compounds for systems treatment of complex diseases, and applied it to colorectal adenocarcinoma. FMCM used multiple functional gene modules to query the Connectivity Map (CMap). The functional modules were built around hub genes identified, through a gene selection by trend-of-disease-progression (GSToP) procedure, from condition-specific gene-gene interaction networks constructed from sets of cohort gene expression microarrays. The candidate drug compounds were restricted to drugs exhibiting predicted minimal intracellular harmful side effects. We tested FMCM against the common practice of selecting drugs using a genomic signature represented by a single set of individual genes to query CMap (IGCM), and found FMCM to have higher robustness, accuracy, specificity, and reproducibility in identifying known anti-cancer agents. Among the 46 drug candidates selected by FMCM for colorectal adenocarcinoma treatment, 65% had literature support for association with anti-cancer activities, and 60% of the drugs predicted to have harmful effects on cancer had been reported to be associated with carcinogens/immune suppressors. Compounds were formed from the selected drug candidates where in each compound the component drugs collectively were beneficial to all the functional modules while no single component drug was harmful to any of the modules. In cell viability tests, we identified four candidate drugs: GW-8510, etacrynic acid, ginkgolide A, and 6-azathymine, as having high inhibitory activities against cancer cells. Through microarray experiments we confirmed the novel functional links predicted for three candidate drugs: phenoxybenzamine (broad effects), GW-8510 (cell cycle), and imipenem (immune system). We believe FMCM can be usefully applied to repurposed drug discovery for systems treatment of other types of cancer and other complex diseases.

We derive an expression with four adjustable parameters that reproduces well the 20x20 Miyazawa-Jernigan potential matrix extracted from known protein structures. The numerical values of the parameters can be approximately computed from the surface tension of water, water-screened dipole interactions between residues and water and among residues, and average exposures of residues in folded proteins.

We consider quantum holonomy of some three-dimensional general covariant non-Abelian field theory in Landau gauge and confirm a previous result partially proven. We show that quantum holonomy retains metric independence after explicit gauge fixing and hence possesses the topological property of a link invariant. We examine the generalized quantum holonomy defined on a multi-component link and discuss its relation to a polynomial for the link., Comment: RevTex, 12 pages. The metric independence of path integral measure is justified and the case of multi-component link is discussed in detail. To be published in Physical Review D

We show that dipole-dipole interactions induced by gravitational force and possibly ion-stream drag force give rise to stable triangular and oriented cubic crystalline structures recently observed in a dusty plasma, as opposed to only unoriented cubic close-packed structures usually expected of Wigner crystals. In certain cases the dipole interaction may flatten the crystal significantly. We calculate the phase diagrams of the crystals and analyze and explain some of their features. {copyright} {ital 1997} {ital The American Physical Society}

We apply differential renormalization method to the study of three-dimensional topologically massive Yang-Mills and Chern-Simons theories. The method is especially suitable for such theories as it avoids the need for dimensional continuation of three-dimensional antisymmetric tensor and the Feynman rules for three-dimensional theories in coordinate space are relatively simple. The calculus involved is still lengthy but not as difficult as other existing methods of calculation. We compute one-loop propagators and vertices and derive the one-loop local effective action for topologically massive Yang-Mills theory. We then consider Chern-Simons field theory as the large mass limit of topologically massive Yang-Mills theory and show that this leads to the famous shift in the parameter $k$. Some useful formulas for the calculus of differential renormalization of three-dimensional field theories are given in an Appendix., Comment: 25 pages, 4 figures. Several typewritten errors and inappropriate arguments are corrected, especially the correct adresses of authors are given

We construct a universal tangle invariant on a quantum algebra. We show that the invariant maps tangle to commutants of the algebra; every (1,1)-tangle is mapped to a Casimir operator of the algebra; the eigenvalue of the Casimir operator in an irreducible representation of the algebra is a link polynomial for the closure of the tangle. This result is applied to a discussion of the Alexander - Conway polynomial and quantum holonomy in Chern - Simons theory in three dimensions.

We propose an order index, [Formula: see text], which quantifies the notion of “life at the edge of chaos” when applied to genome sequences. It maps genomes to a number from 0 (random and of infinite length) to 1 (fully ordered) and applies regardless of sequence length and base composition. The 786 complete genomic sequences in GenBank were found to have [Formula: see text] values in a very narrow range, 0.037 ± 0.027. We show this implies that genomes are halfway towards being completely random, namely, at the edge of chaos. We argue that this narrow range represents the neighborhood of a fixed-point in the space of sequences, and genomes are driven there by the dynamics of a robust, predominantly neutral evolution process.

The quantum holonomy associated with a set of contours on a lattice is shown to be a Casimir operator of the gauge group. Its value in an irreducible representation of the group is the unit matrix times a c-number. This assertion is verified numerically on a 4D lattice for the SU(3) pure gauge theory for cases of the set containing one and two contours. The group-valued quantum holonomy contains more useful information than the character-valued Wilson loop in aspects that could be crucial. The quantum holonomy of a set of loops could serve as an observable for measuring the correlations between the gauge loops.

It is shown that in geometric quantization formulation, fractional statistics in a quantized system of N indistinguishable particles in two spatial dimensions arise from the nontrivial cohomology of the flat connection on the quantum line bundles as well as from the nontrivial homology of the configuration space. The propagator of a nonrelativistic interacting system with fractional statistics is derived.

The properties of the Seifert circles in an oriented tangle diagram are exploited to prove a theorem that asserts that every (n,n)-tangle diagram is isotopic to a partially closed braid, and a second one that facilitates the assignment of wrong-way edges, one on each Seifert circle, in a tangle diagram. These result are used to identify the structure of an abstract algebra on which a functor for the isotopy of general tangles may be constructed. Any finite dimensional irreducible representation of a quasitriangular Hopf algebra is a realization of this algebra.

Protein folding dynamics is one of major issues constantly investigated in the study of protein functions. The molecular dynamic (MD) simulation with the replica exchange method (REM) is a common theoretical approach considered. Yet a trade-off in applying the REM is that the dynamics toward the native configuration in the simulations seems lost. In this work, we show that given REM-MD simulation results, protein folding dynamics can be directly derived from laws of inference. The applicability of the resulting approach, the entropic folding dynamics, is illustrated by investigating a well-studied Trp-cage peptide. Our results are qualitatively comparable with those from other studies. The current studies suggest that the incorporation of laws of inference and physics brings in a comprehensive perspective on exploring the protein folding dynamics.

We propose an order index, $\ensuremath{\phi}$, which gives a quantitative measure of randomness and order of complete genomic sequences. It maps genomes to a number from 0 (random and of infinite length) to 1 (fully ordered) and applies regardless of sequence length. The 786 complete genomic sequences in GenBank were found to have $\ensuremath{\phi}$ values in a very narrow range, ${\ensuremath{\phi}}_{g}={0.031}_{\ensuremath{-}0.015}^{+0.028}$. We show this implies that genomes are halfway toward being completely random, or, at the ``edge of chaos.'' We further show that artificial ``genomes'' converted from literary classics have $\ensuremath{\phi}$'s that almost exactly coincide with ${\ensuremath{\phi}}_{g}$, but sequences of low information content do not. We infer that ${\ensuremath{\phi}}_{g}$ represents a high information-capacity ``fixed point'' in sequence space, and that genomes are driven to it by the dynamics of a robust growth and evolution process. We show that a growth process characterized by random segmental duplication can robustly drive genomes to the fixed point.

The cause of symmetry is usually subtle, and its study often leads to a deeper understanding of the bearer of the symmetry. To gain insight into the dynamics driving the growth and evolution of genomes, we conducted a comprehensive study of textual symmetries in 786 complete chromosomes. We focused on symmetry based on our belief that, in spite of their extreme diversity, genomes must share common dynamical principles and mechanisms that drive their growth and evolution, and that the most robust footprints of such dynamics are symmetry related. We found that while complement and reverse symmetries are essentially absent in genomic sequences, inverse–complement plus reverse–symmetry is prevalent in complex patterns in most chromosomes, a vast majority of which have near maximum global inverse symmetry. We also discovered relations that can quantitatively account for the long observed but unexplained phenomenon of -mer skews in genomes. Our results suggest segmental and whole-genome inverse duplications are important mechanisms in genome growth and evolution, probably because they are efficient means by which the genome can exploit its double-stranded structure to enrich its code-inventory.

Magnetoencephalography (MEG) provides dynamic spatial-temporal insight of neural activities in the cortex. Because the number of possible sources is far greater than the number of MEG detectors, the proposition to localize sources directly from MEG data is notoriously ill-posed. Here we develop an approach based on data processing procedures including clustering, forward and backward filtering, and the method of maximum entropy. We show that taking as a starting point the assumption that the sources lie in the general area of the auditory cortex (an area of about 40 mm by 15 mm), our approach is capable of achieving reasonable success in pinpointing active sources concentrated in an area of a few mm's across, while limiting the spatial distribution and number of false positives., 11 pages, 15 figures

In the template-assistance model, normal prion protein (PrPC), the pathogenic cause of prion diseases such as Creutzfeldt-Jakob (CJD) in human, Bovine Spongiform Encephalopathy (BSE) in cow, and scrapie in sheep, converts to infectious prion (PrPSc) through an autocatalytic process triggered by a transient interaction between PrPC and PrPSc. Conventional studies suggest the S1-H1-S2 region in PrPC to be the template of S1-S2 $\beta$-sheet in PrPSc, and the conformational conversion of PrPC into PrPSc may involve an unfolding of H1 in PrPC and its refolding into the $\beta$-sheet in PrPSc. Here we conduct a series of simulation experiments to test the idea of transient interaction of the template-assistance model. We find that the integrity of H1 in PrPC is vulnerable to a transient interaction that alters the native dihedral angles at residue Asn$^{143}$, which connects the S1 flank to H1, but not to interactions that alter the internal structure of the S1 flank, nor to those that alter the relative orientation between H1 and the S2 flank., Comment: A major revision on statistical analysis method has been made. The paper now has 23 pages, 11 figures. This work was presented at 2006 APS March meeting session K29.0004 at Baltimore, MD, USA 3/13-17, 2006. This paper has been accepted for pubcliation in European Biophysical Journal on Feb 2, 2009

New braid group (bn) representations of the D2 and D3 types are obtained by solving the defining relations of bn directly. The authors discuss a procedure (Baxterization) which allows one to construct their corresponding quantum R matrices.

Based on the sine-Gordon formulation of one-dimensional Coulomb gas with a relaxation length scale l0, a simple model for the deconfinement phase transition is proposed. The model gives a simulation of the deconfinement in the quark-antiquark system.

Etude d'un gaz de Coulomb bidimensionnel, fondee sur une fonctionnelle d'onde gaussienne ou une methode gaussienne de potentiel effectif. Dans le cas de la charge ponctuelle les resultats sont presentes analytiquement. On en deduit les expressions de la raie critique