ABSTRACT
This paper suggests a way to investigate pathological voice signals from nonlinear time series analysis for clinical applications. Primarily, self similar characteristics of vocal signals have been obtained by means of a discrete wavelet analysis. Moreover, the approximate entropy of the signals has been calculated as tools for classification. Furthermore, fuzzy c-means clustering has been employed for voice signal classification. Fuzzy membership function has been proposed as a way of quantifying the amount of disorder. The results show that proposed feature vector and classification method are reliable for voice signal analysis and disorder measurement.
Subject(s)
Algorithms , Diagnosis, Computer-Assisted/methods , Fuzzy Logic , Pattern Recognition, Automated/methods , Sound Spectrography/methods , Speech Production Measurement/methods , Voice Disorders/diagnosis , Humans , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
Ionic polymer-metal composites (IPMCs) have advantages of softness and flexibility to be used in biomedical applications. In this paper a fuzzy logic controller (FLC) has been designed for achieving the goal of tracking. Also co-evolutionary-based genetic algorithms technique has been employed to optimize membership functions and fuzzy rules. The simulation results show that fuzzy controller has higher performance in comparison with other controllers.
Subject(s)
Algorithms , Composite Resins , Metals , Models, Biological , Animals , Humans , Ions , Materials Testing/methodsABSTRACT
Rho-family GTPases transduce signals from receptors leading to changes in cell shape and motility, mitogenesis, and development. Proteins containing the Dbl homology (DH) domain are responsible for activating Rho GTPases by catalyzing the exchange of GDP for GTP. Receptor-initiated stimulation of Dbl protein Vav exchange activity involves tyrosine phosphorylation. We show through structure determination that the mVav1 DH domain is autoinhibited by an N-terminal extension, which lies in the GTPase interaction site. This extension contains the Tyr174 Src-family kinase recognition site, and phosphorylation or truncation of this peptide results in stimulation of GEF activity. NMR spectroscopy data show that the N-terminal peptide is released from the DH domain and becomes unstructured upon phosphorylation. Thus, tyrosine phosphorylation relieves autoinhibition by exposing the GTPase interaction surface of the DH domain, which is obligatory for Vav activation.
Subject(s)
Cell Cycle Proteins , Peptide Fragments/chemistry , Peptide Fragments/metabolism , Phosphotyrosine/metabolism , Proto-Oncogene Proteins/chemistry , Proto-Oncogene Proteins/metabolism , Sequence Homology, Amino Acid , Amino Acid Motifs , Animals , Binding Sites , Enzyme Activation , Feedback , Guanosine Triphosphate/metabolism , Mice , Models, Biological , Models, Molecular , Nuclear Magnetic Resonance, Biomolecular , Phosphorylation , Protein Structure, Secondary , Protein Structure, Tertiary , Proto-Oncogene Proteins c-vav , Structure-Activity Relationship , cdc42 GTP-Binding Protein/metabolism , rac1 GTP-Binding Protein/metabolism , src-Family Kinases/metabolismABSTRACT
An iterative, outlier exclusion, second-order surface fitting algorithm has been developed to solve the well-known phase wraparound problem associated with in vivo applications of the three-point Dixon magnetic resonance imaging method. The technique was optimized for speed by reducing the problem to a pair of planar fits. The spatial misalignment between water and fat components due to the chemical shift was handled on a subpixel level by invoking the shift theorem of Fourier transformation. From the chemical shift corrected water and fat images, high quality recombined MR images were generated. The algorithm was validated in both phantom and patient studies. In vivo breast images and pelvic images are provided as a demonstration of the method.
Subject(s)
Adipose Tissue/metabolism , Image Enhancement/methods , Magnetic Resonance Imaging/methods , Water/metabolism , Adult , Algorithms , Fourier Analysis , Humans , Male , Mammography , Middle Aged , Models, Theoretical , Phantoms, Imaging , Reference ValuesABSTRACT
SH3 and WW domains are involved in a variety of intracellular signaling pathways. Recent work has shed light on the mechanism whereby these signaling modules recognize prolines in polyproline ligands, which has implications in the design of ligands selectively targeting these interactions.
Subject(s)
Deoxyribonucleases, Type II Site-Specific/chemistry , Signal Transduction/physiology , src Homology Domains/genetics , Alkylation , Animals , Humans , LigandsABSTRACT
The Rho-family GTP-hydrolysing proteins (GTPases), Cdc42, Rac and Rho, act as molecular switches in signalling pathways that regulate cytoskeletal architecture, gene expression and progression of the cell cycle. Cdc42 and Rac transmit many signals through GTP-dependent binding to effector proteins containing a Cdc42/Rac-interactive-binding (CRIB) motif. One such effector, the Wiskott-Aldrich syndrome protein (WASP), is postulated to link activation of Cdc42 directly to the rearrangement of actin. Human mutations in WASP cause severe defects in haematopoletic cell function, leading to clinical symptoms of thrombocytopenia, immunodeficiency and eczema. Here we report the solution structure of a complex between activated Cdc42 and a minimal GTPase-binding domain (GBD) from WASP. An extended amino-terminal GBD peptide that includes the CRIB motif contacts the switch I, beta2 and alpha5 regions of Cdc42. A carboxy-terminal beta-hairpin and alpha-helix pack against switch II. The Phe-X-His-X2-His portion of the CRIB motif and the alpha-helix appear to mediate sensitivity to the nucleotide switch through contacts to residues 36-40 of Cdc42. Discrimination between the Rho-family members is likely to be governed by GBD contacts to the switch I and alpha5 regions of the GTPases. Structural and biochemical data suggest that GBD-sequence divergence outside the CRIB motif may reflect additional regulatory interactions with functional domains that are specific to individual effectors.
Subject(s)
Cell Cycle Proteins/chemistry , GTP-Binding Proteins/chemistry , Proteins/chemistry , Wiskott-Aldrich Syndrome , Amino Acid Sequence , Binding Sites , Cell Cycle Proteins/metabolism , Crystallography, X-Ray , Escherichia coli , GTP Phosphohydrolases/chemistry , GTP Phosphohydrolases/metabolism , GTP-Binding Proteins/metabolism , Humans , Models, Molecular , Molecular Sequence Data , Protein Binding , Proteins/metabolism , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism , Sequence Homology, Amino Acid , Wiskott-Aldrich Syndrome Protein , cdc42 GTP-Binding ProteinABSTRACT
Guanine nucleotide exchange factors in the Dbl family activate Rho GTPases by accelerating dissociation of bound GDP, promoting acquisition of the GTP-bound state. Dbl proteins possess a approximately 200 residue catalytic Dbl-homology (DH) domain, that is arranged in tandem with a C-terminal pleckstrin homology (PH) domain in nearly all cases. Here we report the solution structure of the DH domain of human PAK-interacting exchange protein (betaPIX). The domain is composed of 11 alpha-helices that form a flattened, elongated bundle. The structure explains a large body of mutagenesis data, which, along with sequence comparisons, identify the GTPase interaction site as a surface formed by three conserved helices near the center of one face of the domain. Proximity of the site to the DH C-terminus suggests a means by which PH-ligand interactions may be coupled to DH-GTPase interactions to regulate signaling through the Dbl proteins in vivo.
Subject(s)
Blood Proteins/chemistry , Caenorhabditis elegans Proteins , Catalytic Domain/genetics , GTP Phosphohydrolases/metabolism , Phosphoproteins , Proto-Oncogene Proteins/chemistry , Sequence Homology, Amino Acid , Amino Acid Sequence , Blood Proteins/genetics , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Enzyme Activation , Escherichia coli , Frameshift Mutation , GTP Phosphohydrolases/genetics , GTP-Binding Proteins/genetics , GTP-Binding Proteins/metabolism , Guanine Nucleotide Exchange Factors , Guanosine Diphosphate/metabolism , Helminth Proteins/genetics , Helminth Proteins/metabolism , Humans , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Sequence Data , Mutagenesis, Site-Directed , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Proteins/genetics , Proteins/metabolism , Proto-Oncogene Proteins/genetics , Rho Guanine Nucleotide Exchange Factors , Sequence Alignment , cdc42 GTP-Binding Protein , rhoA GTP-Binding ProteinABSTRACT
Spatial maps of the percentage cellularity in pelvic bone marrow were calculated at a resolution of 15.6 mm3 from six volunteers and 10 patients treated for documented hematologic disease using a three-point Dixon MRI pulse sequence. The percentage cellularity calculation was aided by analyzing a two-dimensional feature space consisting of the apparent water fraction (Wa), and the T2 relaxation time of water (T2w). An extracellular water fraction was assigned to each voxel on the basis of a two-component T2w algorithm. In six cases, the method was compared to results obtained from core biopsies or aspirates of the posterior iliac crest. The results indicate that segmentation schemes that combine high-quality phase-contrast imaging with nuclear relaxation time measurements can potentially identify the true fractional marrow volume occupied by hematopoietic elements in a variety of clinical situations.
Subject(s)
Algorithms , Bone Marrow/anatomy & histology , Hematopoiesis , Magnetic Resonance Imaging/methods , Adult , Biopsy , Bone Marrow/physiology , Case-Control Studies , Female , Hematologic Diseases/pathology , Humans , Ilium/pathology , Image Processing, Computer-Assisted , Male , Middle AgedABSTRACT
The Rho GDP-dissociation inhibitors (GDIs) negatively regulate Rho-family GTPases. The inhibitory activity of GDI derives both from an ability to bind the carboxy-terminal isoprene of Rho family members and extract them from membranes, and from inhibition of GTPase cycling between the GTP- and GDP-bound states. Here we demonstrate that these binding and inhibitory functions of rhoGDI can be attributed to two structurally distinct regions of the protein. A carboxy-terminal folded domain of relative molecular mass 16,000 (M[r] 16K) binds strongly to the Rho-family member Cdc42, yet has little effect on the rate of nucleotide dissociation from the GTPase. The solution structure of this domain shows a beta-sandwich motif with a narrow hydrophobic cleft that binds isoprenes, and an exposed surface that interacts with the protein portion of Cdc42. The amino-terminal region of rhoGDI is unstructured in the absence of target and contributes little to binding, but is necessary to inhibit nucleotide dissociation from Cdc42. These results lead to a model of rhoGDI function in which the carboxy-terminal binding domain targets the amino-terminal inhibitory region to GTPases, resulting in membrane extraction and inhibition of nucleotide cycling.
