Analysis of correlated domain motions in IgG light chain reveals possible mechanisms of immunological signal transduction.

PubMed

Król, Marcin; Roterman, Irena; Piekarska, Barbara; Konieczny, Leszek; Rybarska, Janina; Stopa, Barbara; Spólnik, Paweł

2005-05-15

It was shown experimentally that binding of a micelle composed of Congo red molecules to immunological complexes leads to the enhanced stability of the latter, and simultaneously prevents binding of a complement molecule (C1q). The dye binds in a cavity created by the removal of N-terminal polypeptide chain, as observed experimentally in a model system-immunoglobulin G (IgG) light chain dimer. Molecular Dynamics (MD) simulations of three forms of IgG light chain dimer, with and without the dye, were performed to investigate the role of N-terminal fragment and self-assembled ligand in coupling between V and C domains. Root-mean-square distance (RMSD) time profiles show that removal of N-terminal fragment leads to destabilization of V domain. A micelle composed of four self-assembled dye molecules stabilizes and fixes the domain. Analysis of root-mean-square fluctuation (RMSF) values and dynamic cross-correlation matrices (DCCM) reveals that removal of N-terminal fragment results in complete decoupling between V and C domains. Binding of self-assembled Congo red molecules improves the coupling, albeit slightly. The disruption of a small beta-sheet composed of N- and C-terminal fragments of the domain (NC sheet) is the most likely reason for the decoupling. Self-assembled ligand, bound in the place originally occupied by N-terminal fragment, is not able to take over the function of the beta-sheet. Lack of correlation of motions between residues in V and C domains denotes that light chain-Congo red complexes have hampered ability to transmit conformational changes between domains. This is a likely explanation of the lack of complement binding by immunological complexes, which bind Congo red, and supports the idea that the NC sheet is the key structural fragment taking part in immunological signal transduction. Copyright 2005 Wiley-Liss, Inc.

Signal transduction in a covalent post-assembly modification cascade

NASA Astrophysics Data System (ADS)

Pilgrim, Ben S.; Roberts, Derrick A.; Lohr, Thorsten G.; Ronson, Tanya K.; Nitschke, Jonathan R.

2017-12-01

Natural reaction cascades control the movement of biomolecules between cellular compartments. Inspired by these systems, we report a synthetic reaction cascade employing post-assembly modification reactions to direct the partitioning of supramolecular complexes between phases. The system is composed of a self-assembled tetrazine-edged FeII8L12 cube and a maleimide-functionalized FeII4L6 tetrahedron. Norbornadiene (NBD) functions as the stimulus that triggers the cascade, beginning with the inverse-electron-demand Diels-Alder reaction of NBD with the tetrazine moieties of the cube. This reaction generates cyclopentadiene as a transient by-product, acting as a relay signal that subsequently undergoes a Diels-Alder reaction with the maleimide-functionalized tetrahedron. Cyclooctyne can selectively inhibit the cascade by outcompeting NBD as the initial trigger. Initiating the cascade with 2-octadecyl NBD leads to selective alkylation of the tetrahedron upon cascade completion. The increased lipophilicity of the C18-tagged tetrahedron drives this complex into a non-polar phase, allowing its isolation from the initially inseparable mixture of complexes.

Complex noise suppression using a sparse representation and 3D filtering of images

NASA Astrophysics Data System (ADS)

Kravchenko, V. F.; Ponomaryov, V. I.; Pustovoit, V. I.; Palacios-Enriquez, A.

2017-08-01

A novel method for the filtering of images corrupted by complex noise composed of randomly distributed impulses and additive Gaussian noise has been substantiated for the first time. The method consists of three main stages: the detection and filtering of pixels corrupted by impulsive noise, the subsequent image processing to suppress the additive noise based on 3D filtering and a sparse representation of signals in a basis of wavelets, and the concluding image processing procedure to clean the final image of the errors emerged at the previous stages. A physical interpretation of the filtering method under complex noise conditions is given. A filtering block diagram has been developed in accordance with the novel approach. Simulations of the novel image filtering method have shown an advantage of the proposed filtering scheme in terms of generally recognized criteria, such as the structural similarity index measure and the peak signal-to-noise ratio, and when visually comparing the filtered images.

47 CFR 80.1183 - Remote control for maneuvering or navigation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... synchronization signal and a message signal composed of a documentation number group, a company control group, an... control group, composed of three letters taken from AAA through ZZZ, which must be transmitted one time... transmitted one time. (iv) The termination of transmission group, composed of the control character “EM...

47 CFR 80.1183 - Remote control for maneuvering or navigation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... synchronization signal and a message signal composed of a documentation number group, a company control group, an... control group, composed of three letters taken from AAA through ZZZ, which must be transmitted one time... transmitted one time. (iv) The termination of transmission group, composed of the control character “EM...

47 CFR 80.1183 - Remote control for maneuvering or navigation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... synchronization signal and a message signal composed of a documentation number group, a company control group, an... control group, composed of three letters taken from AAA through ZZZ, which must be transmitted one time... transmitted one time. (iv) The termination of transmission group, composed of the control character “EM...

47 CFR 80.1183 - Remote control for maneuvering or navigation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... synchronization signal and a message signal composed of a documentation number group, a company control group, an... control group, composed of three letters taken from AAA through ZZZ, which must be transmitted one time... transmitted one time. (iv) The termination of transmission group, composed of the control character “EM...

47 CFR 80.1183 - Remote control for maneuvering or navigation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... synchronization signal and a message signal composed of a documentation number group, a company control group, an... control group, composed of three letters taken from AAA through ZZZ, which must be transmitted one time... transmitted one time. (iv) The termination of transmission group, composed of the control character “EM...

A computationally identified compound antagonizes excess FGF-23 signaling in renal tubules and a mouse model of hypophosphatemia

DOE PAGES

Xiao, Zhousheng; Riccardi, Demian; Velazquez, Hector A.; ...

2016-11-22

Fibroblast growth factor–23 (FGF-23) interacts with a binary receptor complex composed of α-Klotho (α-KL) and FGF receptors (FGFRs) to regulate phosphate and vitamin D metabolism in the kidney. Excess FGF-23 production, which causes hypophosphatemia, is genetically inherited or occurs with chronic kidney disease. Among other symptoms, hypophosphatemia causes vitamin D deficiency and the bone-softening disorder rickets. Current therapeutics that target the receptor complex have limited utility clinically. In this paper, using a computationally driven, structure-based, ensemble docking and virtual high-throughput screening approach, we identified four novel compounds predicted to selectively inhibit FGF-23–induced activation of the FGFR/α-KL complex. Additional modeling andmore » functional analysis found that Zinc13407541 bound to FGF-23 and disrupted its interaction with the FGFR1/α-KL complex; experiments in a heterologous cell expression system showed that Zinc13407541 selectivity inhibited α-KL–dependent FGF-23 signaling. Zinc13407541 also inhibited FGF-23 signaling in isolated renal tubules ex vivo and partially reversed the hypophosphatemic effects of excess FGF-23 in a mouse model. Finally, these chemical probes provide a platform to develop lead compounds to treat disorders caused by excess FGF-23.« less

A computationally identified compound antagonizes excess FGF-23 signaling in renal tubules and a mouse model of hypophosphatemia.

PubMed

Xiao, Zhousheng; Riccardi, Demian; Velazquez, Hector A; Chin, Ai L; Yates, Charles R; Carrick, Jesse D; Smith, Jeremy C; Baudry, Jerome; Quarles, L Darryl

2016-11-22

Fibroblast growth factor-23 (FGF-23) interacts with a binary receptor complex composed of α-Klotho (α-KL) and FGF receptors (FGFRs) to regulate phosphate and vitamin D metabolism in the kidney. Excess FGF-23 production, which causes hypophosphatemia, is genetically inherited or occurs with chronic kidney disease. Among other symptoms, hypophosphatemia causes vitamin D deficiency and the bone-softening disorder rickets. Current therapeutics that target the receptor complex have limited utility clinically. Using a computationally driven, structure-based, ensemble docking and virtual high-throughput screening approach, we identified four novel compounds predicted to selectively inhibit FGF-23-induced activation of the FGFR/α-KL complex. Additional modeling and functional analysis found that Zinc13407541 bound to FGF-23 and disrupted its interaction with the FGFR1/α-KL complex; experiments in a heterologous cell expression system showed that Zinc13407541 selectivity inhibited α-KL-dependent FGF-23 signaling. Zinc13407541 also inhibited FGF-23 signaling in isolated renal tubules ex vivo and partially reversed the hypophosphatemic effects of excess FGF-23 in a mouse model. These chemical probes provide a platform to develop lead compounds to treat disorders caused by excess FGF-23. Copyright © 2016, American Association for the Advancement of Science.

Genetic analysis of the contribution of LTBP-3 to thoracic aneurysm in Marfan syndrome

PubMed Central

Zilberberg, Lior; Phoon, Colin K. L.; Robertson, Ian; Dabovic, Branka; Ramirez, Francesco; Rifkin, Daniel B.

2015-01-01

Marfan syndrome (MFS) is an autosomal dominant disorder of connective tissue, caused by mutations of the microfibrillar protein fibrillin-1, that predisposes affected individuals to aortic aneurysm and rupture and is associated with increased TGFβ signaling. TGFβ is secreted from cells as a latent complex consisting of TGFβ, the TGFβ propeptide, and a molecule of latent TGFβ binding protein (LTBP). Improper extracellular localization of the latent complex can alter active TGFβ levels, and has been hypothesized as an explanation for enhanced TGFβ signaling observed in MFS. We previously reported the absence of LTBP-3 in matrices lacking fibrillin-1, suggesting that perturbed TGFβ signaling in MFS might be due to defective interaction of latent TGFβ complexes containing LTBP-3 with mutant fibrillin-1 microfibrils. To test this hypothesis, we genetically suppressed Ltbp3 expression in a mouse model of progressively severe MFS. Here, we present evidence that MFS mice lacking LTBP-3 have improved survival, essentially no aneurysms, reduced disruption and fragmentation of medial elastic fibers, and decreased Smad2/3 and Erk1/2 activation in their aortas. These data suggest that, in MFS, improper localization of latent TGFβ complexes composed of LTBP-3 and TGFβ contributes to aortic disease progression. PMID:26494287

A computationally identified compound antagonizes excess FGF-23 signaling in renal tubules and a mouse model of hypophosphatemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiao, Zhousheng; Riccardi, Demian; Velazquez, Hector A.

Fibroblast growth factor–23 (FGF-23) interacts with a binary receptor complex composed of α-Klotho (α-KL) and FGF receptors (FGFRs) to regulate phosphate and vitamin D metabolism in the kidney. Excess FGF-23 production, which causes hypophosphatemia, is genetically inherited or occurs with chronic kidney disease. Among other symptoms, hypophosphatemia causes vitamin D deficiency and the bone-softening disorder rickets. Current therapeutics that target the receptor complex have limited utility clinically. In this paper, using a computationally driven, structure-based, ensemble docking and virtual high-throughput screening approach, we identified four novel compounds predicted to selectively inhibit FGF-23–induced activation of the FGFR/α-KL complex. Additional modeling andmore » functional analysis found that Zinc13407541 bound to FGF-23 and disrupted its interaction with the FGFR1/α-KL complex; experiments in a heterologous cell expression system showed that Zinc13407541 selectivity inhibited α-KL–dependent FGF-23 signaling. Zinc13407541 also inhibited FGF-23 signaling in isolated renal tubules ex vivo and partially reversed the hypophosphatemic effects of excess FGF-23 in a mouse model. Finally, these chemical probes provide a platform to develop lead compounds to treat disorders caused by excess FGF-23.« less

Roles of mTOR Signaling in Brain Development.

PubMed

Lee, Da Yong

2015-09-01

mTOR is a serine/threonine kinase composed of multiple protein components. Intracellular signaling of mTOR complexes is involved in many of physiological functions including cell survival, proliferation and differentiation through the regulation of protein synthesis in multiple cell types. During brain development, mTOR-mediated signaling pathway plays a crucial role in the process of neuronal and glial differentiation and the maintenance of the stemness of neural stem cells. The abnormalities in the activity of mTOR and its downstream signaling molecules in neural stem cells result in severe defects of brain developmental processes causing a significant number of brain disorders, such as pediatric brain tumors, autism, seizure, learning disability and mental retardation. Understanding the implication of mTOR activity in neural stem cells would be able to provide an important clue in the development of future brain developmental disorder therapies.

Hsp90α forms a stable complex at the cilium neck for the interaction of signalling molecules in IGF-1 receptor signalling.

PubMed

Wang, Hongzhong; Zou, Xinle; Wei, Zhuang; Wu, Yuan; Li, Rongxia; Zeng, Rong; Chen, Zhengjun; Liao, Kan

2015-01-01

The primary cilium is composed of an axoneme that protrudes from the cell surface, a basal body beneath the membrane and a transition neck in between. It is a sensory organelle on the plasma membrane, involved in mediating extracellular signals. In the transition neck region of the cilium, the microtubules change from triplet to doublet microtubules. This region also contains the transition fibres that crosslink the axoneme with the membrane and the necklace proteins that regulate molecules being transported into and out of the cilium. In this protein-enriched, complex area it is important to maintain the correct assembly of all of these proteins. Here, through immunofluorescent staining and protein isolation, we identify the molecular chaperone Hsp90α clustered at the periciliary base. At the transition neck region, phosphorylated Hsp90α forms a stable ring around the axoneme. Heat shock treatment causes Hsp90α to dissipate and induces resorption of cilia. We further identify that Hsp90α at the transition neck region represents a signalling platform on which IRS-1 interacts with intracellular downstream signalling molecules involved in IGF-1 receptor signalling. © 2015. Published by The Company of Biologists Ltd.

Interactions of the chemotaxis signal protein CheY with bacterial flagellar motors visualized by evanescent wave microscopy.

PubMed

Khan, S; Pierce, D; Vale, R D

The chemotaxis signal protein CheY of enteric bacteria shuttles between transmembrane methyl-accepting chemotaxis protein (MCP) receptor complexes and flagellar basal bodies [1]. The basal body C-rings, composed of the FliM, FliG and FliN proteins, form the rotor of the flagellar motor [2]. Phosphorylated CheY binds to isolated FliM [3] and may also interact with FliG [4], but its binding to basal bodies has not been measured. Using the chemorepellent acetate to phosphorylate and acetylate CheY [5], we have measured the covalent-modification-dependent binding of a green fluorescent protein-CheY fusion (GFP-CheY) to motor assemblies in bacteria lacking MCP complexes by evanescent wave microscopy [6]. At acetate concentrations that cause solely clockwise rotation, GFP-CheY molecules bound to native basal bodies or to overproduced rotor complexes with a stoichiometry comparable to the number of C-ring subunits. GFP-CheY did not bind to rotors lacking FIiM/FliN, showing that these subunits are essential for the association. This assay provides a new means of monitoring protein-protein interactions in signal transduction pathways in living cells.

Microscopic insight into thermodynamics of conformational changes of SAP-SLAM complex in signal transduction cascade

NASA Astrophysics Data System (ADS)

Samanta, Sudipta; Mukherjee, Sanchita

2017-04-01

The signalling lymphocytic activation molecule (SLAM) family of receptors, expressed by an array of immune cells, associate with SLAM-associated protein (SAP)-related molecules, composed of single SH2 domain architecture. SAP activates Src-family kinase Fyn after SLAM ligation, resulting in a SLAM-SAP-Fyn complex, where, SAP binds the Fyn SH3 domain that does not involve canonical SH3 or SH2 interactions. This demands insight into this SAP mediated signalling cascade. Thermodynamics of the conformational changes are extracted from the histograms of dihedral angles obtained from the all-atom molecular dynamics simulations of this structurally well characterized SAP-SLAM complex. The results incorporate the binding induced thermodynamic changes of individual amino acid as well as the secondary structural elements of the protein and the solvent. Stabilization of the peptide partially comes through a strong hydrogen bonding network with the protein, while hydrophobic interactions also play a significant role where the peptide inserts itself into a hydrophobic cavity of the protein. SLAM binding widens SAP's second binding site for Fyn, which is the next step in the signal transduction cascade. The higher stabilization and less fluctuation of specific residues of SAP in the Fyn binding site, induced by SAP-SLAM complexation, emerge as the key structural elements to trigger the recognition of SAP by the SH3 domain of Fyn. The thermodynamic quantification of the protein due to complexation not only throws deeper understanding in the established mode of SAP-SLAM interaction but also assists in the recognition of the relevant residues of the protein responsible for alterations in its activity.

Microscopic insight into thermodynamics of conformational changes of SAP-SLAM complex in signal transduction cascade.

PubMed

Samanta, Sudipta; Mukherjee, Sanchita

2017-04-28

The signalling lymphocytic activation molecule (SLAM) family of receptors, expressed by an array of immune cells, associate with SLAM-associated protein (SAP)-related molecules, composed of single SH2 domain architecture. SAP activates Src-family kinase Fyn after SLAM ligation, resulting in a SLAM-SAP-Fyn complex, where, SAP binds the Fyn SH3 domain that does not involve canonical SH3 or SH2 interactions. This demands insight into this SAP mediated signalling cascade. Thermodynamics of the conformational changes are extracted from the histograms of dihedral angles obtained from the all-atom molecular dynamics simulations of this structurally well characterized SAP-SLAM complex. The results incorporate the binding induced thermodynamic changes of individual amino acid as well as the secondary structural elements of the protein and the solvent. Stabilization of the peptide partially comes through a strong hydrogen bonding network with the protein, while hydrophobic interactions also play a significant role where the peptide inserts itself into a hydrophobic cavity of the protein. SLAM binding widens SAP's second binding site for Fyn, which is the next step in the signal transduction cascade. The higher stabilization and less fluctuation of specific residues of SAP in the Fyn binding site, induced by SAP-SLAM complexation, emerge as the key structural elements to trigger the recognition of SAP by the SH3 domain of Fyn. The thermodynamic quantification of the protein due to complexation not only throws deeper understanding in the established mode of SAP-SLAM interaction but also assists in the recognition of the relevant residues of the protein responsible for alterations in its activity.

Assembly of the Human Signal Recognition Particle

NASA Astrophysics Data System (ADS)

Menichelli, Elena; Nagai, Kiyoshi

Large RNA-protein complexes (ribonucleoprotein particles or RNPs) control fundamental biological processes. Their correct assembly is essential for function and occurs by the ordered addition of proteins to the RNA. A good model system for studying RNP assembly is provided by the Signal Recognition Particle (SRP), an RNP conserved from bacteria to humans, with different degrees of complexity. Human SRP, composed of a single RNA molecule and six pro teins, is responsible for the co-translational targeting of secretory and membrane proteins to the endoplasmic reticulum membrane. In vitro studies reveal that the SRP proteins need to be added to the RNA sequentially. If the order of addition is altered, non-native particles are formed. The sequential association of proteins causes conformational changes in the RNA, allowing binding of other proteins. The in vivo assembly is regulated by the translocation of precursors between different cellular compartments. In this chapter we review the current understanding of the human SRP assembly mechanism.

Deciphering complex dynamics of water counteraction around secondary structural elements of allosteric protein complex: Case study of SAP-SLAM system in signal transduction cascade

NASA Astrophysics Data System (ADS)

Samanta, Sudipta; Mukherjee, Sanchita

2018-01-01

The first hydration shell of a protein exhibits heterogeneous behavior owing to several attributes, majorly local polarity and structural flexibility as revealed by solvation dynamics of secondary structural elements. We attempt to recognize the change in complex water counteraction generated due to substantial alteration in flexibility during protein complex formation. The investigation is carried out with the signaling lymphocytic activation molecule (SLAM) family of receptors, expressed by an array of immune cells, and interacting with SLAM-associated protein (SAP), composed of one SH2 domain. All atom molecular dynamics simulations are employed to the aqueous solutions of free SAP and SLAM-peptide bound SAP. We observed that water dynamics around different secondary structural elements became highly affected as well as nicely correlated with the SLAM-peptide induced change in structural rigidity obtained by thermodynamic quantification. A few instances of contradictory dynamic features of water to the change in structural flexibility are explained by means of occluded polar residues by the peptide. For βD, EFloop, and BGloop, both structural flexibility and solvent accessibility of the residues confirm the obvious contribution. Most importantly, we have quantified enhanced restriction in water dynamics around the second Fyn-binding site of the SAP due to SAP-SLAM complexation, even prior to the presence of Fyn. This observation leads to a novel argument that SLAM induced more restricted water molecules could offer more water entropic contribution during the subsequent Fyn binding and provide enhanced stability to the SAP-Fyn complex in the signaling cascade. Finally, SLAM induced water counteraction around the second binding site of the SAP sheds light on the allosteric property of the SAP, which becomes an integral part of the underlying signal transduction mechanism.

Deciphering complex dynamics of water counteraction around secondary structural elements of allosteric protein complex: Case study of SAP-SLAM system in signal transduction cascade.

PubMed

Samanta, Sudipta; Mukherjee, Sanchita

2018-01-28

The first hydration shell of a protein exhibits heterogeneous behavior owing to several attributes, majorly local polarity and structural flexibility as revealed by solvation dynamics of secondary structural elements. We attempt to recognize the change in complex water counteraction generated due to substantial alteration in flexibility during protein complex formation. The investigation is carried out with the signaling lymphocytic activation molecule (SLAM) family of receptors, expressed by an array of immune cells, and interacting with SLAM-associated protein (SAP), composed of one SH2 domain. All atom molecular dynamics simulations are employed to the aqueous solutions of free SAP and SLAM-peptide bound SAP. We observed that water dynamics around different secondary structural elements became highly affected as well as nicely correlated with the SLAM-peptide induced change in structural rigidity obtained by thermodynamic quantification. A few instances of contradictory dynamic features of water to the change in structural flexibility are explained by means of occluded polar residues by the peptide. For βD, EFloop, and BGloop, both structural flexibility and solvent accessibility of the residues confirm the obvious contribution. Most importantly, we have quantified enhanced restriction in water dynamics around the second Fyn-binding site of the SAP due to SAP-SLAM complexation, even prior to the presence of Fyn. This observation leads to a novel argument that SLAM induced more restricted water molecules could offer more water entropic contribution during the subsequent Fyn binding and provide enhanced stability to the SAP-Fyn complex in the signaling cascade. Finally, SLAM induced water counteraction around the second binding site of the SAP sheds light on the allosteric property of the SAP, which becomes an integral part of the underlying signal transduction mechanism.

Signaling at the Golgi During Mitosis

PubMed Central

Colanzi, Antonino; Sütterlin, Christine

2014-01-01

The Golgi complex of mammalian cells is composed of interconnected stacks of flattened cisternae that form a continuous membrane system in the pericentriolar region of the cell. At the onset of mitosis, this so-called Golgi ribbon is converted into small tubular–vesicular clusters in a tightly regulated fragmentation process, which leads to a temporary loss of the physical Golgi–centrosome proximity. Mitotic Golgi breakdown is required for Golgi partitioning into the two daughter cells, cell cycle progression and may contribute to the dispersal of Golgi-associated signaling molecules. Here, we review our current understanding of the mechanisms that control mitotic Golgi reorganization, its biological significance, and assays that are used to study this process. PMID:24295319

Overall Architecture of the Intraflagellar Transport (IFT)-B Complex Containing Cluap1/IFT38 as an Essential Component of the IFT-B Peripheral Subcomplex.

PubMed

Katoh, Yohei; Terada, Masaya; Nishijima, Yuya; Takei, Ryota; Nozaki, Shohei; Hamada, Hiroshi; Nakayama, Kazuhisa

2016-05-20

Intraflagellar transport (IFT) is essential for assembly and maintenance of cilia and flagella as well as ciliary motility and signaling. IFT is mediated by multisubunit complexes, including IFT-A, IFT-B, and the BBSome, in concert with kinesin and dynein motors. Under high salt conditions, purified IFT-B complex dissociates into a core subcomplex composed of at least nine subunits and at least five peripherally associated proteins. Using the visible immunoprecipitation assay, which we recently developed as a convenient protein-protein interaction assay, we determined the overall architecture of the IFT-B complex, which can be divided into core and peripheral subcomplexes composed of 10 and 6 subunits, respectively. In particular, we identified TTC26/IFT56 and Cluap1/IFT38, neither of which was included with certainty in previous models of the IFT-B complex, as integral components of the core and peripheral subcomplexes, respectively. Consistent with this, a ciliogenesis defect of Cluap1-deficient mouse embryonic fibroblasts was rescued by exogenous expression of wild-type Cluap1 but not by mutant Cluap1 lacking the binding ability to other IFT-B components. The detailed interaction map as well as comparison of subcellular localization of IFT-B components between wild-type and Cluap1-deficient cells provides insights into the functional relevance of the architecture of the IFT-B complex. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Overall Architecture of the Intraflagellar Transport (IFT)-B Complex Containing Cluap1/IFT38 as an Essential Component of the IFT-B Peripheral Subcomplex*

PubMed Central

Katoh, Yohei; Terada, Masaya; Nishijima, Yuya; Takei, Ryota; Nozaki, Shohei; Hamada, Hiroshi; Nakayama, Kazuhisa

2016-01-01

Intraflagellar transport (IFT) is essential for assembly and maintenance of cilia and flagella as well as ciliary motility and signaling. IFT is mediated by multisubunit complexes, including IFT-A, IFT-B, and the BBSome, in concert with kinesin and dynein motors. Under high salt conditions, purified IFT-B complex dissociates into a core subcomplex composed of at least nine subunits and at least five peripherally associated proteins. Using the visible immunoprecipitation assay, which we recently developed as a convenient protein-protein interaction assay, we determined the overall architecture of the IFT-B complex, which can be divided into core and peripheral subcomplexes composed of 10 and 6 subunits, respectively. In particular, we identified TTC26/IFT56 and Cluap1/IFT38, neither of which was included with certainty in previous models of the IFT-B complex, as integral components of the core and peripheral subcomplexes, respectively. Consistent with this, a ciliogenesis defect of Cluap1-deficient mouse embryonic fibroblasts was rescued by exogenous expression of wild-type Cluap1 but not by mutant Cluap1 lacking the binding ability to other IFT-B components. The detailed interaction map as well as comparison of subcellular localization of IFT-B components between wild-type and Cluap1-deficient cells provides insights into the functional relevance of the architecture of the IFT-B complex. PMID:26980730

The Development and Application of Random Matrix Theory in Adaptive Signal Processing in the Sample Deficient Regime

DTIC Science & Technology

2014-09-01

optimal diagonal loading which minimizes the MSE. The be- havior of optimal diagonal loading when the arrival process is composed of plane waves embedded...observation vectors. The examples of the ensemble correlation matrix corresponding to the input process consisting of a single or multiple plane waves...Y ∗ij is a complex-conjugate of Yij. This result is used in order to evaluate the expectations of different quadratic forms. The Poincare -Nash

Demonstration of a Specific Escherichia coli SecY–Signal Peptide Interaction†

PubMed Central

Wang, Ligong; Miller, Alexander; Rusch, Sharyn L.; Kendall, Debra A.

2011-01-01

Protein translocation in Escherichia coli is initiated by the interaction of a preprotein with the membrane translocase composed of a motor protein, SecA ATPase, and a membrane-embedded channel, the SecYEG complex. The extent to which the signal peptide region of the preprotein plays a role in SecYEG interactions is unclear, in part because studies in this area typically employ the entire preprotein. Using a synthetic signal peptide harboring a photoaffinity label in its hydrophobic core, we examined this interaction with SecYEG in a detergent micellar environment. The signal peptide was found to specifically bind SecY in a saturable manner and at levels comparable to those that stimulate SecA ATPase activity. Chemical and proteolytic cleavage of cross-linked SecY and analysis of the signal peptide adducts indicate that the binding was primarily to regions of the protein containing transmembrane domains seven and two. The signal peptide–SecY interaction was affected by the presence of SecA and nucleotides in a manner consistent with the transfer of signal peptide to SecY upon nucleotide hydrolysis at SecA. PMID:15476412

Dissecting the Calcium-Induced Differentiation of Human Primary Keratinocytes Stem Cells by Integrative and Structural Network Analyses

PubMed Central

Toufighi, Kiana; Yang, Jae-Seong; Luis, Nuno Miguel; Aznar Benitah, Salvador; Lehner, Ben; Serrano, Luis; Kiel, Christina

2015-01-01

The molecular details underlying the time-dependent assembly of protein complexes in cellular networks, such as those that occur during differentiation, are largely unexplored. Focusing on the calcium-induced differentiation of primary human keratinocytes as a model system for a major cellular reorganization process, we look at the expression of genes whose products are involved in manually-annotated protein complexes. Clustering analyses revealed only moderate co-expression of functionally related proteins during differentiation. However, when we looked at protein complexes, we found that the majority (55%) are composed of non-dynamic and dynamic gene products (‘di-chromatic’), 19% are non-dynamic, and 26% only dynamic. Considering three-dimensional protein structures to predict steric interactions, we found that proteins encoded by dynamic genes frequently interact with a common non-dynamic protein in a mutually exclusive fashion. This suggests that during differentiation, complex assemblies may also change through variation in the abundance of proteins that compete for binding to common proteins as found in some cases for paralogous proteins. Considering the example of the TNF-α/NFκB signaling complex, we suggest that the same core complex can guide signals into diverse context-specific outputs by addition of time specific expressed subunits, while keeping other cellular functions constant. Thus, our analysis provides evidence that complex assembly with stable core components and competition could contribute to cell differentiation. PMID:25946651

Flowers help bees cope with uncertainty: signal detection and the function of floral complexity

PubMed Central

Leonard, Anne S.; Dornhaus, Anna; Papaj, Daniel R.

2011-01-01

Plants often attract pollinators with floral displays composed of visual, olfactory, tactile and gustatory stimuli. Since pollinators' responses to each of these stimuli are usually studied independently, the question of why plants produce multi-component floral displays remains relatively unexplored. Here we used signal detection theory to test the hypothesis that complex displays reduce a pollinator's uncertainty about the floral signal. Specifically, we asked whether one component of the floral display, scent, improved a bee's certainty about the value of another component, color hue. We first trained two groups of bumble bees (Bombus impatiens Cresson) to discriminate between rewarding and unrewarding artificial flowers of slightly different hues in the presence vs absence of scent. In a test phase, we presented these bees with a gradient of floral hues and assessed their ability to identify the hue rewarded during training. We interpreted the extent to which bees' preferences were biased away from the unrewarding hue (‘peak shift’) as an indicator of uncertainty in color discrimination. Our data show that the presence of an olfactory signal reduces uncertainty regarding color: not only was color learning facilitated on scented flowers but also bees showed a lower amount of peak shift in the presence of scent. We explore potential mechanisms by which scent might reduce uncertainty about color, and discuss the broader significance of our results for our understanding of signal evolution. PMID:21147975

Speedup computation of HD-sEMG signals using a motor unit-specific electrical source model.

PubMed

Carriou, Vincent; Boudaoud, Sofiane; Laforet, Jeremy

2018-01-23

Nowadays, bio-reliable modeling of muscle contraction is becoming more accurate and complex. This increasing complexity induces a significant increase in computation time which prevents the possibility of using this model in certain applications and studies. Accordingly, the aim of this work is to significantly reduce the computation time of high-density surface electromyogram (HD-sEMG) generation. This will be done through a new model of motor unit (MU)-specific electrical source based on the fibers composing the MU. In order to assess the efficiency of this approach, we computed the normalized root mean square error (NRMSE) between several simulations on single generated MU action potential (MUAP) using the usual fiber electrical sources and the MU-specific electrical source. This NRMSE was computed for five different simulation sets wherein hundreds of MUAPs are generated and summed into HD-sEMG signals. The obtained results display less than 2% error on the generated signals compared to the same signals generated with fiber electrical sources. Moreover, the computation time of the HD-sEMG signal generation model is reduced to about 90% compared to the fiber electrical source model. Using this model with MU electrical sources, we can simulate HD-sEMG signals of a physiological muscle (hundreds of MU) in less than an hour on a classical workstation. Graphical Abstract Overview of the simulation of HD-sEMG signals using the fiber scale and the MU scale. Upscaling the electrical source to the MU scale reduces the computation time by 90% inducing only small deviation of the same simulated HD-sEMG signals.

Emerging roles of post-translational modifications in signal transduction and angiogenesis.

PubMed

Rahimi, Nader; Costello, Catherine E

2015-01-01

The vascular endothelial growth factor receptor-2 (VEGFR-2) belongs to the family of receptor tyrosine kinases and is a key player in vasculogenesis and pathological angiogenesis. An emerging picture of PTMs of VEGFR-2 suggests that they play central roles in generating a highly dynamic and complex signaling system that regulates key angiogenic responses ranging from endothelial cell differentiation, proliferation, migration to permeability. Recent MS analysis of VEGFR-2 uncovered previously unrecognized PTMs on VEGFR-2 with a distinct function. The ligand binding extracellular domain of VEGFR-2 is composed of seven immunoglobulin-like domains highly decorated with N-glycosylation, while its cytoplasmic domain is subject to multiple PTMs including Tyr, Ser/Thr phosphorylation, Arg and Lys methylation, acetylation and ubiquitination. Here we review the PTMs on VEGFR-2, their importance in angiogenic signaling relays and possible novel therapeutic potentials. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Neurodegeneration in Alzheimer disease: role of amyloid precursor protein and presenilin 1 intracellular signaling.

PubMed

Nizzari, Mario; Thellung, Stefano; Corsaro, Alessandro; Villa, Valentina; Pagano, Aldo; Porcile, Carola; Russo, Claudio; Florio, Tullio

2012-01-01

Alzheimer disease (AD) is a heterogeneous neurodegenerative disorder characterized by (1) progressive loss of synapses and neurons, (2) intracellular neurofibrillary tangles, composed of hyperphosphorylated Tau protein, and (3) amyloid plaques. Genetically, AD is linked to mutations in few proteins amyloid precursor protein (APP) and presenilin 1 and 2 (PS1 and PS2). The molecular mechanisms underlying neurodegeneration in AD as well as the physiological function of APP are not yet known. A recent theory has proposed that APP and PS1 modulate intracellular signals to induce cell-cycle abnormalities responsible for neuronal death and possibly amyloid deposition. This hypothesis is supported by the presence of a complex network of proteins, clearly involved in the regulation of signal transduction mechanisms that interact with both APP and PS1. In this review we discuss the significance of novel finding related to cell-signaling events modulated by APP and PS1 in the development of neurodegeneration.

Detection of Naja atra Cardiotoxin Using Adenosine-Based Molecular Beacon.

PubMed

Shi, Yi-Jun; Chen, Ying-Jung; Hu, Wan-Ping; Chang, Long-Sen

2017-01-07

This study presents an adenosine (A)-based molecular beacon (MB) for selective detection of Naja atra cardiotoxin (CTX) that functions by utilizing the competitive binding between CTX and the poly(A) stem of MB to coralyne. The 5'- and 3'-end of MB were labeled with a reporter fluorophore and a non-fluorescent quencher, respectively. Coralyne induced formation of the stem-loop MB structure through A₂-coralyne-A₂ coordination, causing fluorescence signal turn-off due to fluorescence resonance energy transfer between the fluorophore and quencher. CTX3 could bind to coralyne. Moreover, CTX3 alone induced the folding of MB structure and quenching of MB fluorescence. Unlike that of snake venom α-neurotoxins, the fluorescence signal of coralyne-MB complexes produced a bell-shaped concentration-dependent curve in the presence of CTX3 and CTX isotoxins; a turn-on fluorescence signal was noted when CTX concentration was ≤80 nM, while a turn-off fluorescence signal was noted with a further increase in toxin concentrations. The fluorescence signal of coralyne-MB complexes yielded a bell-shaped curve in response to varying concentrations of N. atra crude venom but not those of Bungarus multicinctus and Protobothrops mucrosquamatus venoms. Moreover, N. nigricollis venom also functioned as N. atra venom to yield a bell-shaped concentration-dependent curve of MB fluorescence signal, again supporting that the hairpin-shaped MB could detect crude venoms containing CTXs. Taken together, our data validate that a platform composed of coralyne-induced stem-loop MB structure selectively detects CTXs.

Oligomers of Amyloid β Prevent Physiological Activation of the Cellular Prion Protein-Metabotropic Glutamate Receptor 5 Complex by Glutamate in Alzheimer Disease.

PubMed

Haas, Laura T; Strittmatter, Stephen M

2016-08-12

The dysfunction and loss of synapses in Alzheimer disease are central to dementia symptoms. We have recently demonstrated that pathological Amyloid β oligomer (Aβo) regulates the association between intracellular protein mediators and the synaptic receptor complex composed of cellular prion protein (PrP(C)) and metabotropic glutamate receptor 5 (mGluR5). Here we sought to determine whether Aβo alters the physiological signaling of the PrP(C)-mGluR5 complex upon glutamate activation. We provide evidence that acute exposure to Aβo as well as chronic expression of familial Alzheimer disease mutant transgenes in model mice prevents protein-protein interaction changes of the complex induced by the glutamate analog 3,5-dihydroxyphenylglycine. We further show that 3,5-dihydroxyphenylglycine triggers the phosphorylation and activation of protein-tyrosine kinase 2-β (PTK2B, also referred to as Pyk2) and of calcium/calmodulin-dependent protein kinase II in wild-type brain slices but not in Alzheimer disease transgenic brain slices or wild-type slices incubated with Aβo. This study further distinguishes two separate Aβo-dependent signaling cascades, one dependent on extracellular Ca(2+) and Fyn kinase activation and the other dependent on the release of Ca(2+) from intracellular stores. Thus, Aβo triggers multiple distinct PrP(C)-mGluR5-dependent events implicated in neurodegeneration and dementia. We propose that targeting the PrP(C)-mGluR5 complex will reverse aberrant Aβo-triggered states of the complex to allow physiological fluctuations of glutamate signaling. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Construction and Experimental Validation of a Petri Net Model of Wnt/β-Catenin Signaling.

PubMed

Jacobsen, Annika; Heijmans, Nika; Verkaar, Folkert; Smit, Martine J; Heringa, Jaap; van Amerongen, Renée; Feenstra, K Anton

2016-01-01

The Wnt/β-catenin signaling pathway is important for multiple developmental processes and tissue maintenance in adults. Consequently, deregulated signaling is involved in a range of human diseases including cancer and developmental defects. A better understanding of the intricate regulatory mechanism and effect of physiological (active) and pathophysiological (hyperactive) WNT signaling is important for predicting treatment response and developing novel therapies. The constitutively expressed CTNNB1 (commonly and hereafter referred to as β-catenin) is degraded by a destruction complex, composed of amongst others AXIN1 and GSK3. The destruction complex is inhibited during active WNT signaling, leading to β-catenin stabilization and induction of β-catenin/TCF target genes. In this study we investigated the mechanism and effect of β-catenin stabilization during active and hyperactive WNT signaling in a combined in silico and in vitro approach. We constructed a Petri net model of Wnt/β-catenin signaling including main players from the plasma membrane (WNT ligands and receptors), cytoplasmic effectors and the downstream negative feedback target gene AXIN2. We validated that our model can be used to simulate both active (WNT stimulation) and hyperactive (GSK3 inhibition) signaling by comparing our simulation and experimental data. We used this experimentally validated model to get further insights into the effect of the negative feedback regulator AXIN2 upon WNT stimulation and observed an attenuated β-catenin stabilization. We furthermore simulated the effect of APC inactivating mutations, yielding a stabilization of β-catenin levels comparable to the Wnt-pathway activities observed in colorectal and breast cancer. Our model can be used for further investigation and viable predictions of the role of Wnt/β-catenin signaling in oncogenesis and development.

Construction and Experimental Validation of a Petri Net Model of Wnt/β-Catenin Signaling

PubMed Central

Heijmans, Nika; Verkaar, Folkert; Smit, Martine J.; Heringa, Jaap

2016-01-01

The Wnt/β-catenin signaling pathway is important for multiple developmental processes and tissue maintenance in adults. Consequently, deregulated signaling is involved in a range of human diseases including cancer and developmental defects. A better understanding of the intricate regulatory mechanism and effect of physiological (active) and pathophysiological (hyperactive) WNT signaling is important for predicting treatment response and developing novel therapies. The constitutively expressed CTNNB1 (commonly and hereafter referred to as β-catenin) is degraded by a destruction complex, composed of amongst others AXIN1 and GSK3. The destruction complex is inhibited during active WNT signaling, leading to β-catenin stabilization and induction of β-catenin/TCF target genes. In this study we investigated the mechanism and effect of β-catenin stabilization during active and hyperactive WNT signaling in a combined in silico and in vitro approach. We constructed a Petri net model of Wnt/β-catenin signaling including main players from the plasma membrane (WNT ligands and receptors), cytoplasmic effectors and the downstream negative feedback target gene AXIN2. We validated that our model can be used to simulate both active (WNT stimulation) and hyperactive (GSK3 inhibition) signaling by comparing our simulation and experimental data. We used this experimentally validated model to get further insights into the effect of the negative feedback regulator AXIN2 upon WNT stimulation and observed an attenuated β-catenin stabilization. We furthermore simulated the effect of APC inactivating mutations, yielding a stabilization of β-catenin levels comparable to the Wnt-pathway activities observed in colorectal and breast cancer. Our model can be used for further investigation and viable predictions of the role of Wnt/β-catenin signaling in oncogenesis and development. PMID:27218469

Crystallization of a 2:2 complex of granulocyte-colony stimulating factor (GCSF) with the ligand-binding region of the GCSF receptor

PubMed Central

Honjo, Eijiro; Tamada, Taro; Maeda, Yoshitake; Koshiba, Takumi; Matsukura, Yasuko; Okamoto, Tomoyuki; Ishibashi, Matsujiro; Tokunaga, Masao; Kuroki, Ryota

2005-01-01

The granulocyte-colony stimulating factor (GCSF) receptor receives signals for regulating the maturation, proliferation and differentiation of the precursor cells of neutrophilic granulocytes. The signalling complex composed of two GCSFs (GCSF, 19 kDa) and two GCSF receptors (GCSFR, 34 kDa) consisting of an Ig-like domain and a cytokine-receptor homologous (CRH) domain was crystallized. A crystal of the complex was grown in 1.0 M sodium formate and 0.1 M sodium acetate pH 4.6 and belongs to space group P41212 (or its enantiomorph P43212), with unit-cell parameters a = b = 110.1, c = 331.8 Å. Unfortunately, this crystal form did not diffract beyond 5 Å resolution. Since the heterogeneity of GCSF receptor appeared to prevent the growth of good-quality crystals, the GCSF receptor was fractionated by anion-exchange chromatography. Crystals of the GCSF–fractionated GCSF receptor complex were grown as a new crystal form in 0.2 M ammonium phosphate. This new crystal form diffracted to beyond 3.0 Å resolution and belonged to space group P3121 (or its enantiomorph P3221), with unit-cell parameters a = b = 134.8, c = 105.7 Å. PMID:16511159

Signalling Network Construction for Modelling Plant Defence Response

PubMed Central

Miljkovic, Dragana; Stare, Tjaša; Mozetič, Igor; Podpečan, Vid; Petek, Marko; Witek, Kamil; Dermastia, Marina; Lavrač, Nada; Gruden, Kristina

2012-01-01

Plant defence signalling response against various pathogens, including viruses, is a complex phenomenon. In resistant interaction a plant cell perceives the pathogen signal, transduces it within the cell and performs a reprogramming of the cell metabolism leading to the pathogen replication arrest. This work focuses on signalling pathways crucial for the plant defence response, i.e., the salicylic acid, jasmonic acid and ethylene signal transduction pathways, in the Arabidopsis thaliana model plant. The initial signalling network topology was constructed manually by defining the representation formalism, encoding the information from public databases and literature, and composing a pathway diagram. The manually constructed network structure consists of 175 components and 387 reactions. In order to complement the network topology with possibly missing relations, a new approach to automated information extraction from biological literature was developed. This approach, named Bio3graph, allows for automated extraction of biological relations from the literature, resulting in a set of (component1, reaction, component2) triplets and composing a graph structure which can be visualised, compared to the manually constructed topology and examined by the experts. Using a plant defence response vocabulary of components and reaction types, Bio3graph was applied to a set of 9,586 relevant full text articles, resulting in 137 newly detected reactions between the components. Finally, the manually constructed topology and the new reactions were merged to form a network structure consisting of 175 components and 524 reactions. The resulting pathway diagram of plant defence signalling represents a valuable source for further computational modelling and interpretation of omics data. The developed Bio3graph approach, implemented as an executable language processing and graph visualisation workflow, is publically available at http://ropot.ijs.si/bio3graph/and can be utilised for modelling other biological systems, given that an adequate vocabulary is provided. PMID:23272172

Circadian desynchronization

PubMed Central

Granada, Adrián E.; Cambras, Trinitat; Díez-Noguera, Antoni; Herzel, Hanspeter

2011-01-01

The suprachiasmatic nucleus (SCN) coordinates via multiple outputs physiological and behavioural circadian rhythms. The SCN is composed of a heterogeneous network of coupled oscillators that entrain to the daily light–dark cycles. Outside the physiological entrainment range, rich locomotor patterns of desynchronized rhythms are observed. Previous studies interpreted these results as the output of different SCN neural subpopulations. We find, however, that even a single periodically driven oscillator can induce such complex desynchronized locomotor patterns. Using signal analysis, we show how the observed patterns can be consistently clustered into two generic oscillatory interaction groups: modulation and superposition. In seven of 17 rats undergoing forced desynchronization, we find a theoretically predicted third spectral component. Combining signal analysis with the theory of coupled oscillators, we provide a framework for the study of circadian desynchronization. PMID:22419981

The nuclear retention signal of HPV16 L2 protein is essential for incoming viral genome to transverse the trans-Golgi network

PubMed Central

DiGiuseppe, Stephen; Bienkowska-Haba, Malgorzata; Hilbig, Lydia; Sapp, Martin

2014-01-01

The Human papillomavirus (HPV) capsid is composed of the major and minor capsid proteins, L1 and L2, respectively. Infectious entry requires a complex series of conformational changes in both proteins that lead to uptake and allow uncoating to occur. During entry, the capsid is disassembled and host cyclophilins dissociate L1 protein from the L2/DNA complex. Herein, we describe a mutant HPV16 L2 protein (HPV16 L2-R302/5A) that traffics pseudogenome to the trans-Golgi network (TGN) but fails to egress. Our data provide further evidence that HPV16 traffics through the TGN and demonstrates that L2 is essential for TGN egress. Furthermore, we show that cyclophilin activity is required for the L2/DNA complex to be transported to the TGN which is accompanied by a reduced L1 protein levels. PMID:24928042

Network representations of immune system complexity

PubMed Central

Subramanian, Naeha; Torabi-Parizi, Parizad; Gottschalk, Rachel A.; Germain, Ronald N.; Dutta, Bhaskar

2015-01-01

The mammalian immune system is a dynamic multi-scale system composed of a hierarchically organized set of molecular, cellular and organismal networks that act in concert to promote effective host defense. These networks range from those involving gene regulatory and protein-protein interactions underlying intracellular signaling pathways and single cell responses to increasingly complex networks of in vivo cellular interaction, positioning and migration that determine the overall immune response of an organism. Immunity is thus not the product of simple signaling events but rather non-linear behaviors arising from dynamic, feedback-regulated interactions among many components. One of the major goals of systems immunology is to quantitatively measure these complex multi-scale spatial and temporal interactions, permitting development of computational models that can be used to predict responses to perturbation. Recent technological advances permit collection of comprehensive datasets at multiple molecular and cellular levels while advances in network biology support representation of the relationships of components at each level as physical or functional interaction networks. The latter facilitate effective visualization of patterns and recognition of emergent properties arising from the many interactions of genes, molecules, and cells of the immune system. We illustrate the power of integrating ‘omics’ and network modeling approaches for unbiased reconstruction of signaling and transcriptional networks with a focus on applications involving the innate immune system. We further discuss future possibilities for reconstruction of increasingly complex cellular and organism-level networks and development of sophisticated computational tools for prediction of emergent immune behavior arising from the concerted action of these networks. PMID:25625853

Acoustic and infrasonic measurements of thunder during the HyMeX SOP1 campaign in 2012 and comparison with new modeling results

NASA Astrophysics Data System (ADS)

Lacroix, Arthur; Farges, Thomas; Marchiano, Regis; Coulouvrat, François

2017-04-01

Thunder is composed of complex acoustic waves with a rich infrasonic and audible frequency spectrum. This complexity depends both on the source and the propagation of the wave to the observer. However there is no mutual agreement on the link between the observed spectral content and the generation mechanisms. The objective of this study is to provide new experimental results and their comparison to theoretical investigations. An acoustic station was deployed in Fall 2012 during the first Special Operation Period of the HyMeX project in South of France. This station was composed of 4 microphones arranged in a triangle of 50-m side with one of them at the center and 4 microbarometers arranged in a triangle of 500-m side with one of them co-localized with the central microphone (Defer et al., 2015). During more than 2 months, about ten thunderstorms occurred over the station producing many cloud-to-ground and intracloud flashes. Several thousands of acoustic signals and electromagnetic detections from research and operational lightning location networks were recorded. Our database contains a sufficient number of flashes close to the source (< 1km) to minimize propagation effects and to focus on the source effects. The 3D reconstruction of the acoustical sources using the acoustic signals (from 1 to 40 Hz) shows that these signals are mainly localized inside the lightning channel joining the cloud to the ground and produced during the return stroke phase of the flashes (Gallin et al., 2016). These observations are compatible with a source mechanism due to the thermal expansion associated to the sudden heating of the air in the lightning channel. An original model inspired by Few's string pearl theory (Few, 1969) has been developed. It shows that the tortuous channel geometry explains at least partly the low frequency content of observed thunder spectrum.

Retriever, a multiprotein complex for retromer-independent endosomal cargo recycling

PubMed Central

McNally, Kerrie E.; Faulkner, Rebecca; Steinberg, Florian; Gallon, Matthew; Ghai, Rajesh; Pim, David; Langton, Paul; Pearson, Neil; Danson, Chris M.; Nägele, Heike; Morris, Lindsey M; Singla, Arnika; Overlee, Brittany L; Heesom, Kate J.; Sessions, Richard; Banks, Lawrence; Collins, Brett M; Berger, Imre; Billadeau, Daniel D.; Burstein, Ezra; Cullen, Peter J.

2018-01-01

Following endocytosis and entry into the endosomal network, integral membrane proteins undergo sorting for lysosomal degradation or are alternatively retrieved and recycled back to the cell surface. Here we describe the discovery of an ancient and conserved multi-protein complex which orchestrates cargo retrieval and recycling and importantly, is biochemically and functionally distinct to the established retromer pathway. Composed of a heterotrimer of DSCR3, C16orf62 and VPS29, and bearing striking similarity with retromer, we have called this complex ‘retriever’. We establish that retriever associates with the cargo adaptor sorting nexin 17 (SNX17) and couples to the CCC and WASH complexes to prevent lysosomal degradation and promote cell surface recycling of α5β1-integrin. Through quantitative proteomic analysis we identify over 120 cell surface proteins, including numerous integrins, signalling receptors and solute transporters, which require SNX17-retriever to maintain their surface levels. Our identification of retriever establishes a major new endosomal retrieval and recycling pathway. PMID:28892079

Calculation method of spin accumulations and spin signals in nanostructures using spin resistors

NASA Astrophysics Data System (ADS)

Torres, Williams Savero; Marty, Alain; Laczkowski, Piotr; Jamet, Matthieu; Vila, Laurent; Attané, Jean-Philippe

2018-02-01

Determination of spin accumulations and spin currents is essential for a deep understanding of spin transport in nanostructures and further optimization of spintronic devices. So far, they are easily obtained using different approaches in nanostructures composed of few elements; however their calculation becomes complicated as the number of elements increases. Here, we propose a 1-D spin resistor approach to calculate analytically spin accumulations, spin currents and magneto-resistances in heterostructures. Our method, particularly applied to multi-terminal metallic nanostructures, provides a fast and systematic mean to determine such spin properties in structures where conventional methods remain complex.

Laser pulse coded signal frequency measuring device based on DSP and CPLD

NASA Astrophysics Data System (ADS)

Zhang, Hai-bo; Cao, Li-hua; Geng, Ai-hui; Li, Yan; Guo, Ru-hai; Wang, Ting-feng

2011-06-01

Laser pulse code is an anti-jamming measures used in semi-active laser guided weapons. On account of the laser-guided signals adopting pulse coding mode and the weak signal processing, it need complex calculations in the frequency measurement process according to the laser pulse code signal time correlation to meet the request in optoelectronic countermeasures in semi-active laser guided weapons. To ensure accurately completing frequency measurement in a short time, it needed to carry out self-related process with the pulse arrival time series composed of pulse arrival time, calculate the signal repetition period, and then identify the letter type to achieve signal decoding from determining the time value, number and rank number in a signal cycle by Using CPLD and DSP for signal processing chip, designing a laser-guided signal frequency measurement in the pulse frequency measurement device, improving the signal processing capability through the appropriate software algorithms. In this article, we introduced the principle of frequency measurement of the device, described the hardware components of the device, the system works and software, analyzed the impact of some system factors on the accuracy of the measurement. The experimental results indicated that this system improve the accuracy of the measurement under the premise of volume, real-time, anti-interference, low power of the laser pulse frequency measuring device. The practicality of the design, reliability has been demonstrated from the experimental point of view.

From molecular noise to behavioural variability in a single bacterium

NASA Astrophysics Data System (ADS)

Korobkova, Ekaterina; Emonet, Thierry; Vilar, Jose M. G.; Shimizu, Thomas S.; Cluzel, Philippe

2004-04-01

The chemotaxis network that governs the motion of Escherichia coli has long been studied to gain a general understanding of signal transduction. Although this pathway is composed of just a few components, it exhibits some essential characteristics of biological complexity, such as adaptation and response to environmental signals. In studying intracellular networks, most experiments and mathematical models have assumed that network properties can be inferred from population measurements. However, this approach masks underlying temporal fluctuations of intracellular signalling events. We have inferred fundamental properties of the chemotaxis network from a noise analysis of behavioural variations in individual bacteria. Here we show that certain properties established by population measurements, such as adapted states, are not conserved at the single-cell level: for timescales ranging from seconds to several minutes, the behaviour of non-stimulated cells exhibit temporal variations much larger than the expected statistical fluctuations. We find that the signalling network itself causes this noise and identify the molecular events that produce it. Small changes in the concentration of one key network component suppress temporal behavioural variability, suggesting that such variability is a selected property of this adaptive system.

Adaptive hybrid control of manipulators

NASA Technical Reports Server (NTRS)

Seraji, H.

1987-01-01

Simple methods for the design of adaptive force and position controllers for robot manipulators within the hybrid control architecuture is presented. The force controller is composed of an adaptive PID feedback controller, an auxiliary signal and a force feedforward term, and it achieves tracking of desired force setpoints in the constraint directions. The position controller consists of adaptive feedback and feedforward controllers and an auxiliary signal, and it accomplishes tracking of desired position trajectories in the free directions. The controllers are capable of compensating for dynamic cross-couplings that exist between the position and force control loops in the hybrid control architecture. The adaptive controllers do not require knowledge of the complex dynamic model or parameter values of the manipulator or the environment. The proposed control schemes are computationally fast and suitable for implementation in on-line control with high sampling rates.

The design of multi-core DSP parallel model based on message passing and multi-level pipeline

NASA Astrophysics Data System (ADS)

Niu, Jingyu; Hu, Jian; He, Wenjing; Meng, Fanrong; Li, Chuanrong

2017-10-01

Currently, the design of embedded signal processing system is often based on a specific application, but this idea is not conducive to the rapid development of signal processing technology. In this paper, a parallel processing model architecture based on multi-core DSP platform is designed, and it is mainly suitable for the complex algorithms which are composed of different modules. This model combines the ideas of multi-level pipeline parallelism and message passing, and summarizes the advantages of the mainstream model of multi-core DSP (the Master-Slave model and the Data Flow model), so that it has better performance. This paper uses three-dimensional image generation algorithm to validate the efficiency of the proposed model by comparing with the effectiveness of the Master-Slave and the Data Flow model.

Biosignals learning and synthesis using deep neural networks.

PubMed

Belo, David; Rodrigues, João; Vaz, João R; Pezarat-Correia, Pedro; Gamboa, Hugo

2017-09-25

Modeling physiological signals is a complex task both for understanding and synthesize biomedical signals. We propose a deep neural network model that learns and synthesizes biosignals, validated by the morphological equivalence of the original ones. This research could lead the creation of novel algorithms for signal reconstruction in heavily noisy data and source detection in biomedical engineering field. The present work explores the gated recurrent units (GRU) employed in the training of respiration (RESP), electromyograms (EMG) and electrocardiograms (ECG). Each signal is pre-processed, segmented and quantized in a specific number of classes, corresponding to the amplitude of each sample and fed to the model, which is composed by an embedded matrix, three GRU blocks and a softmax function. This network is trained by adjusting its internal parameters, acquiring the representation of the abstract notion of the next value based on the previous ones. The simulated signal was generated by forecasting a random value and re-feeding itself. The resulting generated signals are similar with the morphological expression of the originals. During the learning process, after a set of iterations, the model starts to grasp the basic morphological characteristics of the signal and later their cyclic characteristics. After training, these models' prediction are closer to the signals that trained them, specially the RESP and ECG. This synthesis mechanism has shown relevant results that inspire the use to characterize signals from other physiological sources.

Bacterial Biofilms as Complex Communities

NASA Astrophysics Data System (ADS)

Vlamakis, Hera

2010-03-01

Many microbial populations form surface-associated multicellular communities known as biofilms. These multicellular communities are encased in a self-produced extracellular matrix composed of polysaccharides and proteins. Division of labor is a key feature of these communities and different cells serve distinct functions. We have found that in biofilms of the bacterium Bacillus subtilis, different cell types including matrix-producing and sporulating cells coexist and localize to distinct regions within the structured community. We were interested in understanding how these different cell types arise. Using fluorescence reporters under the control of promoters that are specific for distinct cell types we were able to follow the dynamics of differentiation throughout biofilm development. We found that a series of extracellular signals leads to differentiation of distinct cell types during biofilm formation. In addition, we found that extracellular matrix functions as a differentiation signal for timely sporulation within a biofilm and mutants unable to produce matrix were delayed in sporulation. Our results indicate that within a biofilm, cell-cell signaling is directional in that one cell type produces a signal that is sensed by another distinct cell type. Furthermore, once differentiated, cells become resistant to the action of other signaling molecules making it possible to maintain distinct cell populations over prolonged periods.

Regulation of Nuclear Import and Export of Negative Cofactor 2*S⃞

PubMed Central

Kahle, Joerg; Piaia, Elisa; Neimanis, Sonja; Meisterernst, Michael; Doenecke, Detlef

2009-01-01

The negative cofactor 2 (NC2) is a protein complex composed of two subunits, NC2α and NC2β, and plays a key role in transcription regulation. Here we investigate whether each subunit contains a nuclear localization signal (NLS) that permits individual crossing of the nuclear membrane or whether nuclear import of NC2α and NC2β depends on heterodimerization. Our results from in vitro binding studies and transfection experiments in cultured cells show that each subunit contains a classical NLS (cNLS) that is recognized by the importin α/β heterodimer. Regardless of the individual cNLSs the two NC2 subunits are translocated as a preassembled complex as co-transfection experiments with wild-type and cNLS-deficient NC2 subunits demonstrate. Ran-dependent binding of the nuclear export receptor Crm1/exportin 1 confirmed the presence of a leucine-rich nuclear export signal (NES) in NC2β. In contrast, NC2α does not exhibit a NES. Our results from interspecies heterokaryon assays suggest that heterodimerization with NC2α masks the NES in NC2β, which prevents nuclear export of the NC2 complex. A mutation in either one of the two cNLSs decreases the extent of importin α/β-mediated nuclear import of the NC2 complex. In addition, the NC2 complex can enter the nucleus via a second pathway, facilitated by importin 13. Because importin 13 binds exclusively to the NC2 complex but not to the individual subunits this alternative import pathway depends on sequence elements distributed among the two subunits. PMID:19204005

Modular assembly of optical nanocircuits.

PubMed

Shi, Jinwei; Monticone, Francesco; Elias, Sarah; Wu, Yanwen; Ratchford, Daniel; Li, Xiaoqin; Alù, Andrea

2014-05-29

A key element enabling the microelectronic technology advances of the past decades has been the conceptualization of complex circuits with versatile functionalities as being composed of the proper combination of basic 'lumped' circuit elements (for example, inductors and capacitors). In contrast, modern nanophotonic systems are still far from a similar level of sophistication, partially because of the lack of modularization of their response in terms of basic building blocks. Here we demonstrate the design, assembly and characterization of relatively complex photonic nanocircuits by accurately positioning a number of metallic and dielectric nanoparticles acting as modular lumped elements. The nanoparticle clusters produce the desired spectral response described by simple circuit rules and are shown to be dynamically reconfigurable by modifying the direction or polarization of impinging signals. Our work represents an important step towards extending the powerful modular design tools of electronic circuits into nanophotonic systems.

Modular assembly of optical nanocircuits

NASA Astrophysics Data System (ADS)

Shi, Jinwei; Monticone, Francesco; Elias, Sarah; Wu, Yanwen; Ratchford, Daniel; Li, Xiaoqin; Alù, Andrea

2014-05-01

A key element enabling the microelectronic technology advances of the past decades has been the conceptualization of complex circuits with versatile functionalities as being composed of the proper combination of basic ‘lumped’ circuit elements (for example, inductors and capacitors). In contrast, modern nanophotonic systems are still far from a similar level of sophistication, partially because of the lack of modularization of their response in terms of basic building blocks. Here we demonstrate the design, assembly and characterization of relatively complex photonic nanocircuits by accurately positioning a number of metallic and dielectric nanoparticles acting as modular lumped elements. The nanoparticle clusters produce the desired spectral response described by simple circuit rules and are shown to be dynamically reconfigurable by modifying the direction or polarization of impinging signals. Our work represents an important step towards extending the powerful modular design tools of electronic circuits into nanophotonic systems.

Interaction of Vascular Smooth Muscle Cells Under Low Shear Stress

NASA Technical Reports Server (NTRS)

Seidel, Charles L.

1998-01-01

The blood vessel wall consists of three cellular layers, an outer adventitial, a middle medial and an inner intimal layer. When the blood vessel forms in the embryo it begins as a tube composed of a single cell type called endothelial cells. Over time, other cells are recruited from the surrounding tissue to form additional layers on the outer surface of the endothelial tube. The cells that are recruited are called mesenchymal cells. Mesenchymal cells are responsible for the production of connective tissue that holds the blood vessel together and for developing into vascular smooth muscle cells that are responsible for regulating the diameter of the vessel (1) and therefore, blood flow. In a fully developed blood vessel, the endothelial cells make- up the majority of cells in the intimal layer while the mesenchymal cells make-up the majority of cells in the medial and adventitial layers. Within the medial layer of a mature vessel, cells are organized into multiple circular layers of alternating bands of connective tissue and cells. The cell layer is composed of a mixture of mesenchymal cells that have not developed into smooth muscle cells and fully developed smooth muscle cells (2). The assembly and organization of complex tissues is directed in part by a signaling system composed of proteins on the cell surface called adhesion molecules. Adhesion molecules enable cells to recognize each other as well as the composition of the connective tissue in which they reside (3). It was hypothesized that the different cell types that compose the vascular wall possess different adhesion molecules that enable them to recognize each other and through this recognition system, form the complex layered organization of the vascular wall. In other words, the layered organization is an intrinsic property of the cells. If this hypothesis is correct then the different cells that make up the vessel wall, when mixed together, should organize themselves into a layered structure resembling an intact blood vessel. Experiments described below were designed to test this hypothesis.

Exploring the Multi-Layered Affordances of Composing and Performing Interactive Music with Responsive Technologies.

PubMed

Einarsson, Anna; Ziemke, Tom

2017-01-01

The question motivating the work presented here, starting from a view of music as embodied and situated activity, is how can we account for the complexity of interactive music performance situations. These are situations in which human performers interact with responsive technologies, such as sensor-driven technology or sound synthesis affected by analysis of the performed sound signal. This requires investigating in detail the underlying mechanisms, but also providing a more holistic approach that does not lose track of the complex whole constituted by the interactions and relationships of composers, performers, audience, technologies, etc. The concept of affordances has frequently been invoked in musical research, which has seen a " bodily turn " in recent years, similar to the development of the embodied cognition approach in the cognitive sciences. We therefore begin by broadly delineating its usage in the cognitive sciences in general, and in music research in particular. We argue that what is still missing in the discourse on musical affordances is an encompassing theoretical framework incorporating the sociocultural dimensions that are fundamental to the situatedness and embodiment of interactive music performance and composition. We further argue that the cultural affordances framework, proposed by Rietveld and Kiverstein (2014) and recently articulated further by Ramstead et al. (2016) in this journal, although not previously applied to music, constitutes a promising starting point. It captures and elucidates this complex web of relationships in terms of shared landscapes and individual fields of affordances. We illustrate this with examples foremost from the first author's artistic work as composer and performer of interactive music. This sheds new light on musical composition as a process of construction-and embodied mental simulation-of situations, guiding the performers' and audience's attention in shifting fields of affordances. More generally, we believe that the theoretical perspectives and concrete examples discussed in this paper help to elucidate how situations-and with them affordances-are dynamically constructed through the interactions of various mechanisms as people engage in embodied and situated activity.

AP-1 subunits: quarrel and harmony among siblings.

PubMed

Hess, Jochen; Angel, Peter; Schorpp-Kistner, Marina

2004-12-01

The AP-1 transcription factor is mainly composed of Jun, Fos and ATF protein dimers. It mediates gene regulation in response to a plethora of physiological and pathological stimuli, including cytokines, growth factors, stress signals, bacterial and viral infections, as well as oncogenic stimuli. Studies in genetically modified mice and cells have highlighted a crucial role for AP-1 in a variety of cellular events involved in normal development or neoplastic transformation causing cancer. However, emerging evidence indicates that the contribution of AP-1 to determination of cell fates critically depends on the relative abundance of AP-1 subunits, the composition of AP-1 dimers, the quality of stimulus, the cell type and the cellular environment. Therefore, AP-1-mediated regulation of processes such as proliferation, differentiation, apoptosis and transformation should be considered within the context of a complex dynamic network of signalling pathways and other nuclear factors that respond simultaneously.

The Neural Border: Induction, Specification and Maturation of the territory that generates Neural Crest cells.

PubMed

Pla, Patrick; Monsoro-Burq, Anne H

2018-05-28

The neural crest is induced at the edge between the neural plate and the nonneural ectoderm, in an area called the neural (plate) border, during gastrulation and neurulation. In recent years, many studies have explored how this domain is patterned, and how the neural crest is induced within this territory, that also participates to the prospective dorsal neural tube, the dorsalmost nonneural ectoderm, as well as placode derivatives in the anterior area. This review highlights the tissue interactions, the cell-cell signaling and the molecular mechanisms involved in this dynamic spatiotemporal patterning, resulting in the induction of the premigratory neural crest. Collectively, these studies allow building a complex neural border and early neural crest gene regulatory network, mostly composed by transcriptional regulations but also, more recently, including novel signaling interactions. Copyright © 2018. Published by Elsevier Inc.

Fast reversible learning based on neurons functioning as anisotropic multiplex hubs

NASA Astrophysics Data System (ADS)

Vardi, Roni; Goldental, Amir; Sheinin, Anton; Sardi, Shira; Kanter, Ido

2017-05-01

Neural networks are composed of neurons and synapses, which are responsible for learning in a slow adaptive dynamical process. Here we experimentally show that neurons act like independent anisotropic multiplex hubs, which relay and mute incoming signals following their input directions. Theoretically, the observed information routing enriches the computational capabilities of neurons by allowing, for instance, equalization among different information routes in the network, as well as high-frequency transmission of complex time-dependent signals constructed via several parallel routes. In addition, this kind of hubs adaptively eliminate very noisy neurons from the dynamics of the network, preventing masking of information transmission. The timescales for these features are several seconds at most, as opposed to the imprint of information by the synaptic plasticity, a process which exceeds minutes. Results open the horizon to the understanding of fast and adaptive learning realities in higher cognitive brain's functionalities.

Causal Structure of Brain Physiology after Brain Injury from Subarachnoid Hemorrhage.

PubMed

Claassen, Jan; Rahman, Shah Atiqur; Huang, Yuxiao; Frey, Hans-Peter; Schmidt, J Michael; Albers, David; Falo, Cristina Maria; Park, Soojin; Agarwal, Sachin; Connolly, E Sander; Kleinberg, Samantha

2016-01-01

High frequency physiologic data are routinely generated for intensive care patients. While massive amounts of data make it difficult for clinicians to extract meaningful signals, these data could provide insight into the state of critically ill patients and guide interventions. We develop uniquely customized computational methods to uncover the causal structure within systemic and brain physiologic measures recorded in a neurological intensive care unit after subarachnoid hemorrhage. While the data have many missing values, poor signal-to-noise ratio, and are composed from a heterogeneous patient population, our advanced imputation and causal inference techniques enable physiologic models to be learned for individuals. Our analyses confirm that complex physiologic relationships including demand and supply of oxygen underlie brain oxygen measurements and that mechanisms for brain swelling early after injury may differ from those that develop in a delayed fashion. These inference methods will enable wider use of ICU data to understand patient physiology.

Tongue and Taste Organ Biology and Function: Homeostasis Maintained by Hedgehog Signaling.

PubMed

Mistretta, Charlotte M; Kumari, Archana

2017-02-10

The tongue is an elaborate complex of heterogeneous tissues with taste organs of diverse embryonic origins. The lingual taste organs are papillae, composed of an epithelium that includes specialized taste buds, the basal lamina, and a lamina propria core with matrix molecules, fibroblasts, nerves, and vessels. Because taste organs are dynamic in cell biology and sensory function, homeostasis requires tight regulation in specific compartments or niches. Recently, the Hedgehog (Hh) pathway has emerged as an essential regulator that maintains lingual taste papillae, taste bud and progenitor cell proliferation and differentiation, and neurophysiological function. Activating or suppressing Hh signaling, with genetic models or pharmacological agents used in cancer treatments, disrupts taste papilla and taste bud integrity and can eliminate responses from taste nerves to chemical stimuli but not to touch or temperature. Understanding Hh regulation of taste organ homeostasis contributes knowledge about the basic biology underlying taste disruptions in patients treated with Hh pathway inhibitors.

How cells explore shape space: a quantitative statistical perspective of cellular morphogenesis.

PubMed

Yin, Zheng; Sailem, Heba; Sero, Julia; Ardy, Rico; Wong, Stephen T C; Bakal, Chris

2014-12-01

Through statistical analysis of datasets describing single cell shape following systematic gene depletion, we have found that the morphological landscapes explored by cells are composed of a small number of attractor states. We propose that the topology of these landscapes is in large part determined by cell-intrinsic factors, such as biophysical constraints on cytoskeletal organization, and reflects different stable signaling and/or transcriptional states. Cell-extrinsic factors act to determine how cells explore these landscapes, and the topology of the landscapes themselves. Informational stimuli primarily drive transitions between stable states by engaging signaling networks, while mechanical stimuli tune, or even radically alter, the topology of these landscapes. As environments fluctuate, the topology of morphological landscapes explored by cells dynamically adapts to these fluctuations. Finally we hypothesize how complex cellular and tissue morphologies can be generated from a limited number of simple cell shapes. © 2014 WILEY Periodicals, Inc.

Construction and analysis of a modular model of caspase activation in apoptosis

PubMed Central

Harrington, Heather A; Ho, Kenneth L; Ghosh, Samik; Tung, KC

2008-01-01

Background A key physiological mechanism employed by multicellular organisms is apoptosis, or programmed cell death. Apoptosis is triggered by the activation of caspases in response to both extracellular (extrinsic) and intracellular (intrinsic) signals. The extrinsic and intrinsic pathways are characterized by the formation of the death-inducing signaling complex (DISC) and the apoptosome, respectively; both the DISC and the apoptosome are oligomers with complex formation dynamics. Additionally, the extrinsic and intrinsic pathways are coupled through the mitochondrial apoptosis-induced channel via the Bcl-2 family of proteins. Results A model of caspase activation is constructed and analyzed. The apoptosis signaling network is simplified through modularization methodologies and equilibrium abstractions for three functional modules. The mathematical model is composed of a system of ordinary differential equations which is numerically solved. Multiple linear regression analysis investigates the role of each module and reduced models are constructed to identify key contributions of the extrinsic and intrinsic pathways in triggering apoptosis for different cell lines. Conclusion Through linear regression techniques, we identified the feedbacks, dissociation of complexes, and negative regulators as the key components in apoptosis. The analysis and reduced models for our model formulation reveal that the chosen cell lines predominately exhibit strong extrinsic caspase, typical of type I cell, behavior. Furthermore, under the simplified model framework, the selected cells lines exhibit different modes by which caspase activation may occur. Finally the proposed modularized model of apoptosis may generalize behavior for additional cells and tissues, specifically identifying and predicting components responsible for the transition from type I to type II cell behavior. PMID:19077196

Chromatin signaling to kinetochores: Trans-regulation of Dam1 methylation by histone H2B ubiquitination

PubMed Central

Latham, John A.; Chosed, Renée J.; Wang, Shanzhi; Dent, Sharon Y.R.

2011-01-01

Summary Histone H3K4 trimethylation by the Set1/MLL family of proteins provides a hallmark for transcriptional activity from yeast to humans. In S. cerevisiae, H3K4 methylation is mediated by the Set1-containing COMPASS complex and is regulated in trans by prior ubiquitination of histone H2BK123. All of the events that regulate H2BK123ub and H3K4me are thought to occur at gene promoters. Here we report that this pathway is indispensable for methylation of the only other known substrate of Set1, K233 in Dam1, at kinetochores. Deletion of RAD6, BRE1, or Paf1 complex members abolishes Dam1 methylation, as does mutation of H2BK123. Our results demonstrate that Set1-mediated methylation is regulated by a general pathway regardless of substrate that is composed of transcriptional regulatory factors functioning independently of transcription. Moreover, our data identify a node of regulatory cross-talk in trans between a histone modification and modification on a non-histone protein, demonstrating that changing chromatin states can signal functional changes in other essential cellular proteins and machineries. PMID:21884933

Detecting critical state before phase transition of complex systems by hidden Markov model

NASA Astrophysics Data System (ADS)

Liu, Rui; Chen, Pei; Li, Yongjun; Chen, Luonan

Identifying the critical state or pre-transition state just before the occurrence of a phase transition is a challenging task, because the state of the system may show little apparent change before this critical transition during the gradual parameter variations. Such dynamics of phase transition is generally composed of three stages, i.e., before-transition state, pre-transition state, and after-transition state, which can be considered as three different Markov processes. Thus, based on this dynamical feature, we present a novel computational method, i.e., hidden Markov model (HMM), to detect the switching point of the two Markov processes from the before-transition state (a stationary Markov process) to the pre-transition state (a time-varying Markov process), thereby identifying the pre-transition state or early-warning signals of the phase transition. To validate the effectiveness, we apply this method to detect the signals of the imminent phase transitions of complex systems based on the simulated datasets, and further identify the pre-transition states as well as their critical modules for three real datasets, i.e., the acute lung injury triggered by phosgene inhalation, MCF-7 human breast cancer caused by heregulin, and HCV-induced dysplasia and hepatocellular carcinoma.

Depth Profiles in Maize ( Zea mays L.) Seeds Studied by Photoacoustic Spectroscopy

NASA Astrophysics Data System (ADS)

Hernández-Aguilar, C.; Domínguez-Pacheco, A.; Cruz-Orea, A.; Zepeda-Bautista, R.

2015-06-01

Photoacoustic spectroscopy (PAS) has been used to analyze agricultural seeds and can be applied to the study of seed depth profiles of these complex samples composed of different structures. The sample depth profile can be obtained through the photoacoustic (PA) signal, amplitude, and phase at different light modulation frequencies. The PA signal phase is more sensitive to changes of thermal properties in layered samples than the PA signal amplitude. Hence, the PA signal phase can also be used to characterize layers at different depths. Thus, the objective of the present study was to obtain the optical absorption spectra of maize seeds ( Zea mays L.) by means of PAS at different light modulation frequencies (17 Hz, 30 Hz, and 50 Hz) and comparing these spectra with the ones obtained from the phase-resolved method in order to separate the optical absorption spectra of seed pericarp and endosperm. The results suggest the possibility of using the phase-resolved method to obtain optical absorption spectra of different seed structures, at different depths, without damaging the seed. Thus, PAS could be a nondestructive method for characterization of agricultural seeds and thus improve quality control in the food industry.

Social context influences chemical communication in D. melanogaster males.

PubMed

Kent, Clement; Azanchi, Reza; Smith, Ben; Formosa, Amanda; Levine, Joel D

2008-09-23

Chemical communication mediates social interactions in insects. For the fruit fly, D. melanogaster, the chemical display is a key fitness trait because it leads to mating. An exchange of cues that resembles a dialogue between males and females is enacted by pheromones, chemical signals that pass between individual flies to alter physiology and behavior. Chemical signals also affect the timing of locomotor activity and sleep. We investigated genetic and environmental determinants of chemical communication. To evaluate the role of the social environment, we extracted a chemical blend from individual males selected from groups composed of one genotype and compared these extracts to those from groups of mixed genotypes. To evaluate the role of the physical environment, these comparisons were performed under a light-dark cycle or in constant darkness. Here, we show that chemical signaling is affected by the social environment, light-dark cycle, and genotype as well as the complex interplay of these variables. Gene-by-environment interactions produce highly significant effects on chemical signaling. We also examined individual responses within the groups. Strikingly, the response of one wild-type fly to another is modulated by the genotypic composition of his neighbors. Chemical signaling in D. melanogaster may be a "fickle" trait that depends on the individual's social background.

Integration of growth factor signals at the c-fos serum response element.

PubMed

Price, M A; Hill, C; Treisman, R

1996-04-29

A transcription factor ternary complex composed of serum response factor (SRF) and a second factor, ternary complex factor (TCF), mediates the response of the c-fos Serum Response Element to growth factors and mitogens. In NIH3T3 fibroblasts, TCF binding is required for transcriptional activation by the SRE in response to activation of the Ras-Raf-ERK pathway. We compared the properties of three members of the TCF family, Elk-1, SAP-1 and SAP-2 (ERP/NET). Although all the proteins contain sequences required for ternary complex formation with SRF, only Elk-1 and SAP-1 appear to interact with the c-fos SRE efficiently in vivo. Each TCF contains a C-terminal activation domain capable of transcriptional activation in response to activation of the Ras-Raf-ERK pathway, and this is dependent on the integrity of S/T-P motifs conserved between all the TCF family members. In contrast, activation of the SRE by whole serum and the mitogenic phospholipid LPA requires SRF binding alone. Constitutively activated members of the Rho subfamily of Ras-like GTPases are also capable of inducing activation of the SRE in the absence of TCF; unlike activated Ras itself, these proteins do not activate the TCFs in NIH3T3 cells. At the SRE, SRF- and TCF-linked signalling pathways act synergistically to potentiate transcription.

Financial technical indicator based on chaotic bagging predictors for adaptive stock selection in Japanese and American markets

NASA Astrophysics Data System (ADS)

Suzuki, Tomoya; Ohkura, Yuushi

2016-01-01

In order to examine the predictability and profitability of financial markets, we introduce three ideas to improve the traditional technical analysis to detect investment timings more quickly. Firstly, a nonlinear prediction model is considered as an effective way to enhance this detection power by learning complex behavioral patterns hidden in financial markets. Secondly, the bagging algorithm can be applied to quantify the confidence in predictions and compose new technical indicators. Thirdly, we also introduce how to select more profitable stocks to improve investment performance by the two-step selection: the first step selects more predictable stocks during the learning period, and then the second step adaptively and dynamically selects the most confident stock showing the most significant technical signal in each investment. Finally, some investment simulations based on real financial data show that these ideas are successful in overcoming complex financial markets.

G-quadruplexes as sensing probes.

PubMed

Ruttkay-Nedecky, Branislav; Kudr, Jiri; Nejdl, Lukas; Maskova, Darina; Kizek, Rene; Adam, Vojtech

2013-11-28

Guanine-rich sequences of DNA are able to create tetrastranded structures known as G-quadruplexes; they are formed by the stacking of planar G-quartets composed of four guanines paired by Hoogsteen hydrogen bonding. G-quadruplexes act as ligands for metal ions and aptamers for various molecules. Interestingly, the G-quadruplexes form a complex with anionic porphyrin hemin and exhibit peroxidase-like activity. This review focuses on overview of sensing techniques based on G-quadruplex complexes with anionic porphyrins for detection of various analytes, including metal ions such as K+, Ca2+, Ag+, Hg2+, Cu2+, Pb2+, Sr2+, organic molecules, nucleic acids, and proteins. Principles of G-quadruplex-based detection methods involve DNA conformational change caused by the presence of analyte which leads to a decrease or an increase in peroxidase activity, fluorescence, or electrochemical signal of the used probe. The advantages of various detection techniques are also discussed.

Extracellular matrix structure.

PubMed

Theocharis, Achilleas D; Skandalis, Spyros S; Gialeli, Chrysostomi; Karamanos, Nikos K

2016-02-01

Extracellular matrix (ECM) is a non-cellular three-dimensional macromolecular network composed of collagens, proteoglycans/glycosaminoglycans, elastin, fibronectin, laminins, and several other glycoproteins. Matrix components bind each other as well as cell adhesion receptors forming a complex network into which cells reside in all tissues and organs. Cell surface receptors transduce signals into cells from ECM, which regulate diverse cellular functions, such as survival, growth, migration, and differentiation, and are vital for maintaining normal homeostasis. ECM is a highly dynamic structural network that continuously undergoes remodeling mediated by several matrix-degrading enzymes during normal and pathological conditions. Deregulation of ECM composition and structure is associated with the development and progression of several pathologic conditions. This article emphasizes in the complex ECM structure as to provide a better understanding of its dynamic structural and functional multipotency. Where relevant, the implication of the various families of ECM macromolecules in health and disease is also presented. Copyright © 2015 Elsevier B.V. All rights reserved.

Principles of Genetic Circuit Design

PubMed Central

Brophy, Jennifer A.N.; Voigt, Christopher A.

2014-01-01

Cells are able to navigate environments, communicate, and build complex patterns by initiating gene expression in response to specific signals. Engineers need to harness this capability to program cells to perform tasks or build chemicals and materials that match the complexity seen in nature. This review describes new tools that aid the construction of genetic circuits. We show how circuit dynamics can be influenced by the choice of regulators and changed with expression “tuning knobs.” We collate the failure modes encountered when assembling circuits, quantify their impact on performance, and review mitigation efforts. Finally, we discuss the constraints that arise from operating within a living cell. Collectively, better tools, well-characterized parts, and a comprehensive understanding of how to compose circuits are leading to a breakthrough in the ability to program living cells for advanced applications, from living therapeutics to the atomic manufacturing of functional materials. PMID:24781324

Gluconacetobacter diazotrophicus PAL5 possesses an active quorum sensing regulatory system.

PubMed

Bertini, Elisa V; Nieto Peñalver, Carlos G; Leguina, Ana C; Irazusta, Verónica P; de Figueroa, Lucía I C

2014-09-01

The endophytic bacterium Gluconacetobacter diazotrophicus colonizes a broad range of host plants. Its plant growth-promoting capability is related to the capacity to perform biological nitrogen fixation, the biosynthesis of siderophores, antimicrobial substances and the solubilization of mineral nutrients. Colonization of and survival in these endophytic niche requires a complex regulatory network. Among these, quorum sensing systems (QS) are signaling mechanisms involved in the control of several genes related to microbial interactions, host colonization and stress survival. G. diazotrophicus PAL5 possesses a QS composed of a luxR and a luxI homolog, and produces eight molecules from the AHL family as QS signals. In this report data are provided showing that glucose concentration modifies the relative levels of these signal molecules. The activity of G. diazotrophicus PAL5 QS is also altered in presence of other carbon sources and under saline stress conditions. Inactivation of the QS system of G. diazotrophicus PAL5 by means of a quorum quenching strategy allowed the identification of extracellular and intracellular proteins under the control of this regulatory mechanism.

Nonlinear mode decomposition: A noise-robust, adaptive decomposition method

NASA Astrophysics Data System (ADS)

Iatsenko, Dmytro; McClintock, Peter V. E.; Stefanovska, Aneta

2015-09-01

The signals emanating from complex systems are usually composed of a mixture of different oscillations which, for a reliable analysis, should be separated from each other and from the inevitable background of noise. Here we introduce an adaptive decomposition tool—nonlinear mode decomposition (NMD)—which decomposes a given signal into a set of physically meaningful oscillations for any wave form, simultaneously removing the noise. NMD is based on the powerful combination of time-frequency analysis techniques—which, together with the adaptive choice of their parameters, make it extremely noise robust—and surrogate data tests used to identify interdependent oscillations and to distinguish deterministic from random activity. We illustrate the application of NMD to both simulated and real signals and demonstrate its qualitative and quantitative superiority over other approaches, such as (ensemble) empirical mode decomposition, Karhunen-Loève expansion, and independent component analysis. We point out that NMD is likely to be applicable and useful in many different areas of research, such as geophysics, finance, and the life sciences. The necessary matlab codes for running NMD are freely available for download.

An efficient ASIC implementation of 16-channel on-line recursive ICA processor for real-time EEG system.

PubMed

Fang, Wai-Chi; Huang, Kuan-Ju; Chou, Chia-Ching; Chang, Jui-Chung; Cauwenberghs, Gert; Jung, Tzyy-Ping

2014-01-01

This is a proposal for an efficient very-large-scale integration (VLSI) design, 16-channel on-line recursive independent component analysis (ORICA) processor ASIC for real-time EEG system, implemented with TSMC 40 nm CMOS technology. ORICA is appropriate to be used in real-time EEG system to separate artifacts because of its highly efficient and real-time process features. The proposed ORICA processor is composed of an ORICA processing unit and a singular value decomposition (SVD) processing unit. Compared with previous work [1], this proposed ORICA processor has enhanced effectiveness and reduced hardware complexity by utilizing a deeper pipeline architecture, shared arithmetic processing unit, and shared registers. The 16-channel random signals which contain 8-channel super-Gaussian and 8-channel sub-Gaussian components are used to analyze the dependence of the source components, and the average correlation coefficient is 0.95452 between the original source signals and extracted ORICA signals. Finally, the proposed ORICA processor ASIC is implemented with TSMC 40 nm CMOS technology, and it consumes 15.72 mW at 100 MHz operating frequency.

Dyes assay for measuring physicochemical parameters.

PubMed

Moczko, Ewa; Meglinski, Igor V; Bessant, Conrad; Piletsky, Sergey A

2009-03-15

A combination of selective fluorescent dyes has been developed for simultaneous quantitative measurements of several physicochemical parameters. The operating principle of the assay is similar to electronic nose and tongue systems, which combine nonspecific or semispecific elements for the determination of diverse analytes and chemometric techniques for multivariate data analysis. The analytical capability of the proposed mixture is engendered by changes in fluorescence signal in response to changes in environment such as pH, temperature, ionic strength, and presence of oxygen. The signal is detected by a three-dimensional spectrofluorimeter, and the acquired data are processed using an artificial neural network (ANN) for multivariate calibration. The fluorescence spectrum of a solution of selected dyes allows discreet reading of emission maxima of all dyes composing the mixture. The variations in peaks intensities caused by environmental changes provide distinctive fluorescence patterns which can be handled in the same way as the signals collected from nose/tongue electrochemical or piezoelectric devices. This optical system opens possibilities for rapid, inexpensive, real-time detection of a multitude of physicochemical parameters and analytes of complex samples.

Cellulose-Derived Oligomers Act as Damage-Associated Molecular Patterns and Trigger Defense-Like Responses1

PubMed Central

Li, Shundai; Zipfel, Cyril

2017-01-01

The plant cell wall, often the site of initial encounters between plants and their microbial pathogens, is composed of a complex mixture of cellulose, hemicellulose, and pectin polysaccharides as well as proteins. The concept of damage-associated molecular patterns (DAMPs) was proposed to describe plant elicitors like oligogalacturonides (OGs), which can be derived by the breakdown of the pectin homogalacturon by pectinases. OGs act via many of the same signaling steps as pathogen- or microbe-associated molecular patterns (PAMPs) to elicit defenses and provide protection against pathogens. Given both the complexity of the plant cell wall and the fact that many pathogens secrete a wide range of cell wall-degrading enzymes, we reasoned that the breakdown products of other cell wall polymers may be similarly biologically active as elicitors and may help to reinforce the perception of danger by plant cells. Our results indicate that oligomers derived from cellulose are perceived as signal molecules in Arabidopsis (Arabidopsis thaliana), triggering a signaling cascade that shares some similarities to responses to well-known elicitors such as chitooligomers and OGs. However, in contrast to other known PAMPs/DAMPs, cellobiose stimulates neither detectable reactive oxygen species production nor callose deposition. Confirming our idea that both PAMPs and DAMPs are likely to cooccur at infection sites, cotreatments of cellobiose with flg22 or chitooligomers led to synergistic increases in gene expression. Thus, the perception of cellulose-derived oligomers may participate in cell wall integrity surveillance and represents an additional layer of signaling following plant cell wall breakdown during cell wall remodeling or pathogen attack. PMID:28242654

Testing the Sensory Drive Hypothesis: Geographic variation in echolocation frequencies of Geoffroy's horseshoe bat (Rhinolophidae: Rhinolophus clivosus)

PubMed Central

Catto, Sarah; Mutumi, Gregory L.; Finger, Nikita; Webala, Paul W.

2017-01-01

Geographic variation in sensory traits is usually influenced by adaptive processes because these traits are involved in crucial life-history aspects including orientation, communication, lineage recognition and mate choice. Studying this variation can therefore provide insights into lineage diversification. According to the Sensory Drive Hypothesis, lineage diversification may be driven by adaptation of sensory systems to local environments. It predicts that acoustic signals vary in association with local climatic conditions so that atmospheric attenuation is minimized and transmission of the signals maximized. To test this prediction, we investigated the influence of climatic factors (specifically relative humidity and temperature) on geographic variation in the resting frequencies of the echolocation pulses of Geoffroy’s horseshoe bat, Rhinolophus clivosus. If the evolution of phenotypic variation in this lineage tracks climate variation, human induced climate change may lead to decreases in detection volumes and a reduction in foraging efficiency. A complex non-linear interaction between relative humidity and temperature affects atmospheric attenuation of sound and principal components composed of these correlated variables were, therefore, used in a linear mixed effects model to assess their contribution to observed variation in resting frequencies. A principal component composed predominantly of mean annual temperature (factor loading of -0.8455) significantly explained a proportion of the variation in resting frequency across sites (P < 0.05). Specifically, at higher relative humidity (around 60%) prevalent across the distribution of R. clivosus, increasing temperature had a strong negative effect on resting frequency. Climatic factors thus strongly influence acoustic signal divergence in this lineage, supporting the prediction of the Sensory Drive Hypothesis. The predicted future increase in temperature due to climate change is likely to decrease the detection volume in echolocating bats and adversely impact their foraging efficiency. PMID:29186147

Testing the Sensory Drive Hypothesis: Geographic variation in echolocation frequencies of Geoffroy's horseshoe bat (Rhinolophidae: Rhinolophus clivosus).

PubMed

Jacobs, David S; Catto, Sarah; Mutumi, Gregory L; Finger, Nikita; Webala, Paul W

2017-01-01

Geographic variation in sensory traits is usually influenced by adaptive processes because these traits are involved in crucial life-history aspects including orientation, communication, lineage recognition and mate choice. Studying this variation can therefore provide insights into lineage diversification. According to the Sensory Drive Hypothesis, lineage diversification may be driven by adaptation of sensory systems to local environments. It predicts that acoustic signals vary in association with local climatic conditions so that atmospheric attenuation is minimized and transmission of the signals maximized. To test this prediction, we investigated the influence of climatic factors (specifically relative humidity and temperature) on geographic variation in the resting frequencies of the echolocation pulses of Geoffroy's horseshoe bat, Rhinolophus clivosus. If the evolution of phenotypic variation in this lineage tracks climate variation, human induced climate change may lead to decreases in detection volumes and a reduction in foraging efficiency. A complex non-linear interaction between relative humidity and temperature affects atmospheric attenuation of sound and principal components composed of these correlated variables were, therefore, used in a linear mixed effects model to assess their contribution to observed variation in resting frequencies. A principal component composed predominantly of mean annual temperature (factor loading of -0.8455) significantly explained a proportion of the variation in resting frequency across sites (P < 0.05). Specifically, at higher relative humidity (around 60%) prevalent across the distribution of R. clivosus, increasing temperature had a strong negative effect on resting frequency. Climatic factors thus strongly influence acoustic signal divergence in this lineage, supporting the prediction of the Sensory Drive Hypothesis. The predicted future increase in temperature due to climate change is likely to decrease the detection volume in echolocating bats and adversely impact their foraging efficiency.

Development of a Position Decoding ASIC for SPECT using Silicon Photomultiplier

NASA Astrophysics Data System (ADS)

Cho, M.; Kim, H.; Lim, K. T.; Cho, G.

2016-01-01

Single Photon Emission Computed Tomography(SPECT) is a widely used diagnosis modality for detecting metabolic diseases. In general, SPECT system is consisted of a sensor, a pre-amplifier, position decoding circuits(PDC) and a data acquisition(DAQ) system. Due to such complexity, it is quite costly to assemble SPECT system by putting discrete components together. Moreover, using discrete components would make the system rather bulky. In this work, we designed a channel module ASIC for SPECT system. This system was composed of a transimpedance amplifier(TIA), comparators and digital logics. In this particular module, a TIA was selected as a preamplifier because the decay time and the rise time are shorter than that of other preamplifier topologies. In the proposed module, the amplified pulse from the TIA was split into two separate signals and each signal was then fed into two comparators with different reference levels, e.g., a low and high level. Then an XOR gate combined the comparator outputs and the output of XOR gate was sent to the suceeding digital logic. Furthermore, the output of each component in the module is composed of a signal packet. The packet includes the information on the energy, the time and the position of the incident photon. The energy and position information of a detected radiation can be derived from the output of the D-flipflop(DFF) in the module via time-over-threshold(TOT). The timing information was measured using a delayed rising edge from the low-level referenced comparator. There are several advantages in developing the channel module ASIC. First of all, the ASIC has only digital outputs and thus a correction circuit for analog signal distortion can be neglected. In addition, it is possible to cut down the system production cost because the volume of the system can be reduced due to the compactness of ASIC. The benefits of channel module is not only limited to SPECT but also beneficial to many other radiation detecting systems.

MICU1 and MICU2 Finely Tune the Mitochondrial Ca2+ Uniporter by Exerting Opposite Effects on MCU Activity

PubMed Central

Patron, Maria; Checchetto, Vanessa; Raffaello, Anna; Teardo, Enrico; Vecellio Reane, Denis; Mantoan, Maura; Granatiero, Veronica; Szabò, Ildikò; De Stefani, Diego; Rizzuto, Rosario

2014-01-01

Summary Mitochondrial calcium accumulation was recently shown to depend on a complex composed of an inner-membrane channel (MCU and MCUb) and regulatory subunits (MICU1, MCUR1, and EMRE). A fundamental property of MCU is low activity at resting cytosolic Ca2+ concentrations, preventing deleterious Ca2+ cycling and organelle overload. Here we demonstrate that these properties are ensured by a regulatory heterodimer composed of two proteins with opposite effects, MICU1 and MICU2, which, both in purified lipid bilayers and in intact cells, stimulate and inhibit MCU activity, respectively. Both MICU1 and MICU2 are regulated by calcium through their EF-hand domains, thus accounting for the sigmoidal response of MCU to [Ca2+] in situ and allowing tight physiological control. At low [Ca2+], the dominant effect of MICU2 largely shuts down MCU activity; at higher [Ca2+], the stimulatory effect of MICU1 allows the prompt response of mitochondria to Ca2+ signals generated in the cytoplasm. PMID:24560927

Structural Basis of Rap Phosphatase Inhibition by Phr Peptides

PubMed Central

Gallego del Sol, Francisca; Marina, Alberto

2013-01-01

Two-component systems, composed of a sensor histidine kinase and an effector response regulator (RR), are the main signal transduction devices in bacteria. In Bacillus, the Rap protein family modulates complex signaling processes mediated by two-component systems, such as competence, sporulation, or biofilm formation, by inhibiting the RR components involved in these pathways. Despite the high degree of sequence homology, Rap proteins exert their activity by two completely different mechanisms of action: inducing RR dephosphorylation or blocking RR binding to its target promoter. However the regulatory mechanism involving Rap proteins is even more complex since Rap activity is antagonized by specific signaling peptides (Phr) through a mechanism that remains unknown at the molecular level. Using X-ray analyses, we determined the structure of RapF, the anti-activator of competence RR ComA, alone and in complex with its regulatory peptide PhrF. The structural and functional data presented herein reveal that peptide PhrF blocks the RapF-ComA interaction through an allosteric mechanism. PhrF accommodates in the C-terminal tetratricopeptide repeat domain of RapF by inducing its constriction, a conformational change propagated by a pronounced rotation to the N-terminal ComA-binding domain. This movement partially disrupts the ComA binding site by triggering the ComA disassociation, whose interaction with RapF is also sterically impaired in the PhrF-induced conformation of RapF. Sequence analyses of the Rap proteins, guided by the RapF-PhrF structure, unveil the molecular basis of Phr recognition and discrimination, allowing us to relax the Phr specificity of RapF by a single residue change. PMID:23526880

LGP2 Synergy with MDA5 in RLR-Mediated RNA Recognition and Antiviral Signaling

PubMed Central

Bruns, Annie M.; Horvath, Curt M.

2015-01-01

Mammalian cells have the ability to recognize virus infection and mount a powerful antiviral response. Pattern recognition receptor proteins detect molecular signatures of virus infection and activate antiviral signaling. The RIG-I-like receptor (RLR) proteins are expressed in the cytoplasm of nearly all cells and specifically recognize virus-derived RNA species as a molecular feature discriminating the pathogen from the host. The RLR family is composed of three homologous proteins, RIG-I, MDA5, and LGP2. All RLRs have the ability to detect virus-derived dsRNA and hydrolyze ATP, but display individual differences in enzymatic activity, intrinsic ability to recognize RNA, and mechanisms of activation. Emerging evidence suggests that MDA5 and RIG-I utilize distinct mechanisms to form oligomeric complexes along dsRNA. Aligning of their signaling domains creates a platform capable of propagating and amplifying antiviral signaling responses. LGP2 with intact ATP hydrolysis is critical for the MDA5-mediated antiviral response, but LGP2 lacks the domains essential for activation of antiviral signaling, leaving the role of LGP2 in antiviral signaling unclear. Recent studies revealed a mechanistic basis of synergy between LGP2 and MDA5 leading to enhanced antiviral signaling. This review briefly summarizes the RLR system, and focuses on the relationship between LGP2 and MDA5, describing in detail how these two proteins work together to detect foreign RNA and generate a fully functional antiviral response. PMID:25794939

Complex cellular logic computation using ribocomputing devices.

PubMed

Green, Alexander A; Kim, Jongmin; Ma, Duo; Silver, Pamela A; Collins, James J; Yin, Peng

2017-08-03

Synthetic biology aims to develop engineering-driven approaches to the programming of cellular functions that could yield transformative technologies. Synthetic gene circuits that combine DNA, protein, and RNA components have demonstrated a range of functions such as bistability, oscillation, feedback, and logic capabilities. However, it remains challenging to scale up these circuits owing to the limited number of designable, orthogonal, high-performance parts, the empirical and often tedious composition rules, and the requirements for substantial resources for encoding and operation. Here, we report a strategy for constructing RNA-only nanodevices to evaluate complex logic in living cells. Our 'ribocomputing' systems are composed of de-novo-designed parts and operate through predictable and designable base-pairing rules, allowing the effective in silico design of computing devices with prescribed configurations and functions in complex cellular environments. These devices operate at the post-transcriptional level and use an extended RNA transcript to co-localize all circuit sensing, computation, signal transduction, and output elements in the same self-assembled molecular complex, which reduces diffusion-mediated signal losses, lowers metabolic cost, and improves circuit reliability. We demonstrate that ribocomputing devices in Escherichia coli can evaluate two-input logic with a dynamic range up to 900-fold and scale them to four-input AND, six-input OR, and a complex 12-input expression (A1 AND A2 AND NOT A1*) OR (B1 AND B2 AND NOT B2*) OR (C1 AND C2) OR (D1 AND D2) OR (E1 AND E2). Successful operation of ribocomputing devices based on programmable RNA interactions suggests that systems employing the same design principles could be implemented in other host organisms or in extracellular settings.

K6 linked polyubiquitylation of FADD by CHIP prevents death inducing signaling complex formation suppressing cell death.

PubMed

Seo, Jinho; Lee, Eun-Woo; Shin, Jihye; Seong, Daehyeon; Nam, Young Woo; Jeong, Manhyung; Lee, Seon-Hyeong; Lee, Cheolju; Song, Jaewhan

2018-05-23

Fas-associated death domain (FADD) is an adaptor protein recruiting complexes of caspase 8 to death ligand receptors to induce extrinsic apoptotic cell death in response to a TNF superfamily member. Although, formation of the complex of FADD and caspase 8 upon death stimuli has been studied in detail, posttranslational modifications fine-tuning these processes have yet to be identified. Here we revealed that K6-linked polyubiquitylation of FADD on lysines 149 and 153 mediated by C terminus HSC70-interacting protein (CHIP) plays an important role in preventing formation of the death inducing signaling complex (DISC), thus leading to the suppression of cell death. Cells depleted of CHIP showed higher sensitivity toward death ligands such as FasL and TRAIL, leading to upregulation of DISC formation composed of a death receptor, FADD, and caspase 8. CHIP was able to bind to FADD, induce K6-linked polyubiquitylation of FADD, and suppress DISC formation. By mass spectrometry, lysines 149 and 153 of FADD were found to be responsible for CHIP-mediated FADD ubiquitylation. FADD mutated at these sites was capable of more potent cell death induction as compared with the wild type and was no longer suppressed by CHIP. On the other hand, CHIP deficient in E3 ligase activity was not capable of suppressing FADD function and of FADD ubiquitylation. CHIP depletion in ME-180 cells induced significant sensitization of these cells toward TRAIL in xenograft analyses. These results imply that K6-linked ubiquitylation of FADD by CHIP is a crucial checkpoint in cytokine-dependent extrinsic apoptosis.

A novel method to accurately locate and count large numbers of steps by photobleaching

PubMed Central

Tsekouras, Konstantinos; Custer, Thomas C.; Jashnsaz, Hossein; Walter, Nils G.; Pressé, Steve

2016-01-01

Photobleaching event counting is a single-molecule fluorescence technique that is increasingly being used to determine the stoichiometry of protein and RNA complexes composed of many subunits in vivo as well as in vitro. By tagging protein or RNA subunits with fluorophores, activating them, and subsequently observing as the fluorophores photobleach, one obtains information on the number of subunits in a complex. The noise properties in a photobleaching time trace depend on the number of active fluorescent subunits. Thus, as fluorophores stochastically photobleach, noise properties of the time trace change stochastically, and these varying noise properties have created a challenge in identifying photobleaching steps in a time trace. Although photobleaching steps are often detected by eye, this method only works for high individual fluorophore emission signal-to-noise ratios and small numbers of fluorophores. With filtering methods or currently available algorithms, it is possible to reliably identify photobleaching steps for up to 20–30 fluorophores and signal-to-noise ratios down to ∼1. Here we present a new Bayesian method of counting steps in photobleaching time traces that takes into account stochastic noise variation in addition to complications such as overlapping photobleaching events that may arise from fluorophore interactions, as well as on-off blinking. Our method is capable of detecting ≥50 photobleaching steps even for signal-to-noise ratios as low as 0.1, can find up to ≥500 steps for more favorable noise profiles, and is computationally inexpensive. PMID:27654946

Electrical delay line multiplexing for pulsed mode radiation detectors

NASA Astrophysics Data System (ADS)

Vinke, Ruud; Yeom, Jung Yeol; Levin, Craig S.

2015-04-01

Medical imaging systems are composed of a large number of position sensitive radiation detectors to provide high resolution imaging. For example, whole-body Positron Emission Tomography (PET) systems are typically composed of thousands of scintillation crystal elements, which are coupled to photosensors. Thus, PET systems greatly benefit from methods to reduce the number of data acquisition channels, in order to reduce the system development cost and complexity. In this paper we present an electrical delay line multiplexing scheme that can significantly reduce the number of readout channels, while preserving the signal integrity required for good time resolution performance. We experimented with two 4 × 4 LYSO crystal arrays, with crystal elements having 3 mm × 3 mm × 5 mm and 3 mm × 3 mm × 20 mm dimensions, coupled to 16 Hamamatsu MPPC S10931-050P SiPM elements. Results show that each crystal could be accurately identified, even in the presence of scintillation light sharing and inter-crystal Compton scatter among neighboring crystal elements. The multiplexing configuration degraded the coincidence timing resolution from ∼243 ps FWHM to ∼272 ps FWHM when 16 SiPM signals were combined into a single channel for the 4 × 4 LYSO crystal array with 3 mm × 3 mm × 20 mm crystal element dimensions, in coincidence with a 3 mm × 3 mm × 5 mm LYSO crystal pixel. The method is flexible to allow multiplexing configurations across different block detectors, and is scalable to an entire ring of detectors.

Arabidopsis G-protein interactome reveals connections to cell wall carbohydrates and morphogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klopffleisch, Karsten; Phan, Nguyen; Chen, Jay

2011-01-01

The heterotrimeric G-protein complex is minimally composed of G{alpha}, G{beta}, and G{gamma} subunits. In the classic scenario, the G-protein complex is the nexus in signaling from the plasma membrane, where the heterotrimeric G-protein associates with heptahelical G-protein-coupled receptors (GPCRs), to cytoplasmic target proteins called effectors. Although a number of effectors are known in metazoans and fungi, none of these are predicted to exist in their canonical forms in plants. To identify ab initio plant G-protein effectors and scaffold proteins, we screened a set of proteins from the G-protein complex using two-hybrid complementation in yeast. After deep and exhaustive interrogation, wemore » detected 544 interactions between 434 proteins, of which 68 highly interconnected proteins form the core G-protein interactome. Within this core, over half of the interactions comprising two-thirds of the nodes were retested and validated as genuine in planta. Co-expression analysis in combination with phenotyping of loss-of-function mutations in a set of core interactome genes revealed a novel role for G-proteins in regulating cell wall modification.« less

Defense Against Pathogens: Structural Insights into the Mechanism of Chitin Induced Activation of Innate Immunity.

PubMed

Squeglia, Flavia; Berisio, Rita; Shibuya, Naoto; Kaku, Hanae

2017-11-24

Pattern recognition receptors on the plant cell surface mediate the recognition of microbe-associated molecular patterns, in a process which activates downstream immune signaling. These receptors are plasma membrane-localized kinases which need to be autophosphorylated to activate downstream responses. Perception of attacks from fungi occurs through recognition of chitin, a polymer of an N-acetylglucosamine which is a characteristic component of the cell walls of fungi. This process is regulated in Arabidopsis by chitin elicitor receptor kinase CERK1. A more complex process characterizes rice, in which regulation of chitin perception is operated by a complex composed of OsCERK1, a homolog of CERK1, and the chitin elicitor binding protein OsCEBiP. Recent literature has provided a mechanistic description of the complex regulation of activation of innate immunity in rice and an advance in the structural description of molecular players involved in this process. This review describes the current status of the understanding of molecular events involved in innate immunity activation in rice. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Arabidopsis G-protein interactome reveals connections to cell wall carbohydrates and morphogenesis.

PubMed

Klopffleisch, Karsten; Phan, Nguyen; Augustin, Kelsey; Bayne, Robert S; Booker, Katherine S; Botella, Jose R; Carpita, Nicholas C; Carr, Tyrell; Chen, Jin-Gui; Cooke, Thomas Ryan; Frick-Cheng, Arwen; Friedman, Erin J; Fulk, Brandon; Hahn, Michael G; Jiang, Kun; Jorda, Lucia; Kruppe, Lydia; Liu, Chenggang; Lorek, Justine; McCann, Maureen C; Molina, Antonio; Moriyama, Etsuko N; Mukhtar, M Shahid; Mudgil, Yashwanti; Pattathil, Sivakumar; Schwarz, John; Seta, Steven; Tan, Matthew; Temp, Ulrike; Trusov, Yuri; Urano, Daisuke; Welter, Bastian; Yang, Jing; Panstruga, Ralph; Uhrig, Joachim F; Jones, Alan M

2011-09-27

The heterotrimeric G-protein complex is minimally composed of Gα, Gβ, and Gγ subunits. In the classic scenario, the G-protein complex is the nexus in signaling from the plasma membrane, where the heterotrimeric G-protein associates with heptahelical G-protein-coupled receptors (GPCRs), to cytoplasmic target proteins called effectors. Although a number of effectors are known in metazoans and fungi, none of these are predicted to exist in their canonical forms in plants. To identify ab initio plant G-protein effectors and scaffold proteins, we screened a set of proteins from the G-protein complex using two-hybrid complementation in yeast. After deep and exhaustive interrogation, we detected 544 interactions between 434 proteins, of which 68 highly interconnected proteins form the core G-protein interactome. Within this core, over half of the interactions comprising two-thirds of the nodes were retested and validated as genuine in planta. Co-expression analysis in combination with phenotyping of loss-of-function mutations in a set of core interactome genes revealed a novel role for G-proteins in regulating cell wall modification.

Arabidopsis G-protein interactome reveals connections to cell wall carbohydrates and morphogenesis

PubMed Central

Klopffleisch, Karsten; Phan, Nguyen; Augustin, Kelsey; Bayne, Robert S; Booker, Katherine S; Botella, Jose R; Carpita, Nicholas C; Carr, Tyrell; Chen, Jin-Gui; Cooke, Thomas Ryan; Frick-Cheng, Arwen; Friedman, Erin J; Fulk, Brandon; Hahn, Michael G; Jiang, Kun; Jorda, Lucia; Kruppe, Lydia; Liu, Chenggang; Lorek, Justine; McCann, Maureen C; Molina, Antonio; Moriyama, Etsuko N; Mukhtar, M Shahid; Mudgil, Yashwanti; Pattathil, Sivakumar; Schwarz, John; Seta, Steven; Tan, Matthew; Temp, Ulrike; Trusov, Yuri; Urano, Daisuke; Welter, Bastian; Yang, Jing; Panstruga, Ralph; Uhrig, Joachim F; Jones, Alan M

2011-01-01

The heterotrimeric G-protein complex is minimally composed of Gα, Gβ, and Gγ subunits. In the classic scenario, the G-protein complex is the nexus in signaling from the plasma membrane, where the heterotrimeric G-protein associates with heptahelical G-protein-coupled receptors (GPCRs), to cytoplasmic target proteins called effectors. Although a number of effectors are known in metazoans and fungi, none of these are predicted to exist in their canonical forms in plants. To identify ab initio plant G-protein effectors and scaffold proteins, we screened a set of proteins from the G-protein complex using two-hybrid complementation in yeast. After deep and exhaustive interrogation, we detected 544 interactions between 434 proteins, of which 68 highly interconnected proteins form the core G-protein interactome. Within this core, over half of the interactions comprising two-thirds of the nodes were retested and validated as genuine in planta. Co-expression analysis in combination with phenotyping of loss-of-function mutations in a set of core interactome genes revealed a novel role for G-proteins in regulating cell wall modification. PMID:21952135

The consequences of the intracellular retention of pathogen-derived T-cell-independent antigens on protein presentation to T cells.

PubMed

Leyva-Cobián, F; Outschoorn, I M; Carrasco-Marín, E; Alvarez-Domínguez, C

1997-10-01

Intracellular pathogens can be considered as particulate antigens chemically composed of a complex mixture of T-cell-dependent antigens (TD) (peptides and proteins) and T-cell-independent antigens (TI) (glycolipids and complex polysaccharides). A large range of saccharides (from oligosaccharides to complex polysaccharides) derived from pathogenic microorganisms are being isolated and characterized. They are currently implicated in signaling systems and concomitant host-parasite relationships. However, there are not many structure-function relationships described for these pathogens. This is particularly true of polysaccharides. In this report we have reviewed the role of defined TI antigens in the processing and presentation of defined TD antigens to specific T cells by antigen-presenting cells (APC). We also considered the importance of some of the chemical characteristics shared by different carbohydrates implicated in the inhibition of antigen presentation. These findings are discussed in relation to the clear immunopathological consequences of long retention periods of complex carbohydrate molecules derived from intracellular parasites inside certain APC and the absence of antigen presentation impairment in physiological situations such as the removal of senescent or damaged red blood cells by splenic macrophages or intracellular accumulation of carbohydrates in colostrum and milk macrophages during lactation.

Adaptative synchronization in multi-output fractional-order complex dynamical networks and secure communications

NASA Astrophysics Data System (ADS)

Mata-Machuca, Juan L.; Aguilar-López, Ricardo

2018-01-01

This work deals with the adaptative synchronization of complex dynamical networks with fractional-order nodes and its application in secure communications employing chaotic parameter modulation. The complex network is composed of multiple fractional-order systems with mismatch parameters and the coupling functions are given to realize the network synchronization. We introduce a fractional algebraic synchronizability condition (FASC) and a fractional algebraic identifiability condition (FAIC) which are used to know if the synchronization and parameters estimation problems can be solved. To overcome these problems, an adaptative synchronization methodology is designed; the strategy consists in proposing multiple receiver systems which tend to follow asymptotically the uncertain transmitters systems. The coupling functions and parameters of the receiver systems are adjusted continually according to a convenient sigmoid-like adaptative controller (SLAC), until the measurable output errors converge to zero, hence, synchronization between transmitter and receivers is achieved and message signals are recovered. Indeed, the stability analysis of the synchronization error is based on the fractional Lyapunov direct method. Finally, numerical results corroborate the satisfactory performance of the proposed scheme by means of the synchronization of a complex network consisting of several fractional-order unified chaotic systems.

Synthesizing a novel genetic sequential logic circuit: a push-on push-off switch

PubMed Central

Lou, Chunbo; Liu, Xili; Ni, Ming; Huang, Yiqi; Huang, Qiushi; Huang, Longwen; Jiang, Lingli; Lu, Dan; Wang, Mingcong; Liu, Chang; Chen, Daizhuo; Chen, Chongyi; Chen, Xiaoyue; Yang, Le; Ma, Haisu; Chen, Jianguo; Ouyang, Qi

2010-01-01

Design and synthesis of basic functional circuits are the fundamental tasks of synthetic biologists. Before it is possible to engineer higher-order genetic networks that can perform complex functions, a toolkit of basic devices must be developed. Among those devices, sequential logic circuits are expected to be the foundation of the genetic information-processing systems. In this study, we report the design and construction of a genetic sequential logic circuit in Escherichia coli. It can generate different outputs in response to the same input signal on the basis of its internal state, and ‘memorize' the output. The circuit is composed of two parts: (1) a bistable switch memory module and (2) a double-repressed promoter NOR gate module. The two modules were individually rationally designed, and they were coupled together by fine-tuning the interconnecting parts through directed evolution. After fine-tuning, the circuit could be repeatedly, alternatively triggered by the same input signal; it functions as a push-on push-off switch. PMID:20212522

Synthesizing a novel genetic sequential logic circuit: a push-on push-off switch.

PubMed

Lou, Chunbo; Liu, Xili; Ni, Ming; Huang, Yiqi; Huang, Qiushi; Huang, Longwen; Jiang, Lingli; Lu, Dan; Wang, Mingcong; Liu, Chang; Chen, Daizhuo; Chen, Chongyi; Chen, Xiaoyue; Yang, Le; Ma, Haisu; Chen, Jianguo; Ouyang, Qi

2010-01-01

Design and synthesis of basic functional circuits are the fundamental tasks of synthetic biologists. Before it is possible to engineer higher-order genetic networks that can perform complex functions, a toolkit of basic devices must be developed. Among those devices, sequential logic circuits are expected to be the foundation of the genetic information-processing systems. In this study, we report the design and construction of a genetic sequential logic circuit in Escherichia coli. It can generate different outputs in response to the same input signal on the basis of its internal state, and 'memorize' the output. The circuit is composed of two parts: (1) a bistable switch memory module and (2) a double-repressed promoter NOR gate module. The two modules were individually rationally designed, and they were coupled together by fine-tuning the interconnecting parts through directed evolution. After fine-tuning, the circuit could be repeatedly, alternatively triggered by the same input signal; it functions as a push-on push-off switch.

Development of automated high throughput single molecular microfluidic detection platform for signal transduction analysis

NASA Astrophysics Data System (ADS)

Huang, Po-Jung; Baghbani Kordmahale, Sina; Chou, Chao-Kai; Yamaguchi, Hirohito; Hung, Mien-Chie; Kameoka, Jun

2016-03-01

Signal transductions including multiple protein post-translational modifications (PTM), protein-protein interactions (PPI), and protein-nucleic acid interaction (PNI) play critical roles for cell proliferation and differentiation that are directly related to the cancer biology. Traditional methods, like mass spectrometry, immunoprecipitation, fluorescence resonance energy transfer, and fluorescence correlation spectroscopy require a large amount of sample and long processing time. "microchannel for multiple-parameter analysis of proteins in single-complex (mMAPS)"we proposed can reduce the process time and sample volume because this system is composed by microfluidic channels, fluorescence microscopy, and computerized data analysis. In this paper, we will present an automated mMAPS including integrated microfluidic device, automated stage and electrical relay for high-throughput clinical screening. Based on this result, we estimated that this automated detection system will be able to screen approximately 150 patient samples in a 24-hour period, providing a practical application to analyze tissue samples in a clinical setting.

Single-Stage Step up/down Driver for Permanent-Magnet Synchronous Machines

NASA Astrophysics Data System (ADS)

Chen, T. R.; Juan, Y. L.; Huang, C. Y.; Kuo, C. T.

2017-11-01

The two-stage circuit composed of a step up/down dc converter and a three-phase voltage source inverter is usually adopted as the electric vehicle’s motor driver. The conventional topology is more complicated. Additional power loss resulted from twice power conversion would also cause lower efficiency. A single-stage step up/down Permanent-Magnet Synchronous Motor driver for Brushless DC (BLDC) Motor is proposed in this study. The number components and circuit complexity are reduced. The low frequency six-step square-wave control is used to reduce the switching losses. In the proposed topology, only one active switch is gated with a high frequency PWM signal for adjusting the rotation speed. The rotor position signals are fed back to calculate the motor speed for digital close-loop control in a MCU. A 600W prototype circuit is constructed to drive a BLDC motor with rated speed 3000 rpm, and can control the speed of six sections.

Self-Organization of Embryonic Genetic Oscillators into Spatiotemporal Wave Patterns

PubMed Central

Tsiairis, Charisios D.; Aulehla, Alexander

2016-01-01

Summary In vertebrate embryos, somites, the precursor of vertebrae, form from the presomitic mesoderm (PSM), which is composed of cells displaying signaling oscillations. Cellular oscillatory activity leads to periodic wave patterns in the PSM. Here, we address the origin of such complex wave patterns. We employed an in vitro randomization and real-time imaging strategy to probe for the ability of cells to generate order from disorder. We found that, after randomization, PSM cells self-organized into several miniature emergent PSM structures (ePSM). Our results show an ordered macroscopic spatial arrangement of ePSM with evidence of an intrinsic length scale. Furthermore, cells actively synchronize oscillations in a Notch-signaling-dependent manner, re-establishing wave-like patterns of gene activity. We demonstrate that PSM cells self-organize by tuning oscillation dynamics in response to surrounding cells, leading to collective synchronization with an average frequency. These findings reveal emergent properties within an ensemble of coupled genetic oscillators. PMID:26871631

Towards non-invasive diagnostic imaging of early-stage Alzheimer's disease

NASA Astrophysics Data System (ADS)

Viola, Kirsten L.; Sbarboro, James; Sureka, Ruchi; de, Mrinmoy; Bicca, Maíra A.; Wang, Jane; Vasavada, Shaleen; Satpathy, Sreyesh; Wu, Summer; Joshi, Hrushikesh; Velasco, Pauline T.; Macrenaris, Keith; Waters, E. Alex; Lu, Chang; Phan, Joseph; Lacor, Pascale; Prasad, Pottumarthi; Dravid, Vinayak P.; Klein, William L.

2015-01-01

One way to image the molecular pathology in Alzheimer's disease is by positron emission tomography using probes that target amyloid fibrils. However, these fibrils are not closely linked to the development of the disease. It is now thought that early-stage biomarkers that instigate memory loss are composed of Aβ oligomers. Here, we report a sensitive molecular magnetic resonance imaging contrast probe that is specific for Aβ oligomers. We attach oligomer-specific antibodies onto magnetic nanostructures and show that the complex is stable and binds to Aβ oligomers on cells and brain tissues to give a magnetic resonance imaging signal. When intranasally administered to an Alzheimer's disease mouse model, the probe readily reached hippocampal Aβ oligomers. In isolated samples of human brain tissue, we observed a magnetic resonance imaging signal that distinguished Alzheimer's disease from controls. Such nanostructures that target neurotoxic Aβ oligomers are potentially useful for evaluating the efficacy of new drugs and ultimately for early-stage Alzheimer's disease diagnosis and disease management.

FGF coordinates air sac development by activation of the EGF ligand Vein through the transcription factor PntP2.

PubMed

Cruz, Josefa; Bota-Rabassedas, Neus; Franch-Marro, Xavier

2015-12-03

How several signaling pathways are coordinated to generate complex organs through regulation of tissue growth and patterning is a fundamental question in developmental biology. The larval trachea of Drosophila is composed of differentiated functional cells and groups of imaginal tracheoblasts that build the adult trachea during metamorphosis. Air sac primordium cells (ASP) are tracheal imaginal cells that form the dorsal air sacs that supply oxygen to the flight muscles of the Drosophila adult. The ASP emerges from the tracheal branch that connects to the wing disc by the activation of both Bnl-FGF/Btl and EGFR signaling pathways. Together, these pathways promote cell migration and proliferation. In this study we demonstrate that Vein (vn) is the EGF ligand responsible for the activation of the EGFR pathway in the ASP. We also find that the Bnl-FGF/Btl pathway regulates the expression of vn through the transcription factor PointedP2 (PntP2). Furthermore, we show that the FGF target gene escargot (esg) attenuates EGFR signaling at the tip cells of the developing ASP, reducing their mitotic rate to allow proper migration. Altogether, our results reveal a link between Bnl-FGF/Btl and EGFR signaling and provide novel insight into how the crosstalk of these pathways regulates migration and growth.

FGF coordinates air sac development by activation of the EGF ligand Vein through the transcription factor PntP2

PubMed Central

Cruz, Josefa; Bota-Rabassedas, Neus; Franch-Marro, Xavier

2015-01-01

How several signaling pathways are coordinated to generate complex organs through regulation of tissue growth and patterning is a fundamental question in developmental biology. The larval trachea of Drosophila is composed of differentiated functional cells and groups of imaginal tracheoblasts that build the adult trachea during metamorphosis. Air sac primordium cells (ASP) are tracheal imaginal cells that form the dorsal air sacs that supply oxygen to the flight muscles of the Drosophila adult. The ASP emerges from the tracheal branch that connects to the wing disc by the activation of both Bnl-FGF/Btl and EGFR signaling pathways. Together, these pathways promote cell migration and proliferation. In this study we demonstrate that Vein (vn) is the EGF ligand responsible for the activation of the EGFR pathway in the ASP. We also find that the Bnl-FGF/Btl pathway regulates the expression of vn through the transcription factor PointedP2 (PntP2). Furthermore, we show that the FGF target gene escargot (esg) attenuates EGFR signaling at the tip cells of the developing ASP, reducing their mitotic rate to allow proper migration. Altogether, our results reveal a link between Bnl-FGF/Btl and EGFR signaling and provide novel insight into how the crosstalk of these pathways regulates migration and growth. PMID:26632449

Immunological Functions of the Membrane Proximal Region of MHC Class II Molecules

PubMed Central

Harton, Jonathan; Jin, Lei; Hahn, Amy; Drake, Jim

2016-01-01

Major histocompatibility complex (MHC) class II molecules present exogenously derived antigen peptides to CD4 T cells, driving activation of naïve T cells and supporting CD4-driven immune functions. However, MHC class II molecules are not inert protein pedestals that simply bind and present peptides. These molecules also serve as multi-functional signaling molecules delivering activation, differentiation, or death signals (or a combination of these) to B cells, macrophages, as well as MHC class II-expressing T cells and tumor cells. Although multiple proteins are known to associate with MHC class II, interaction with STING (stimulator of interferon genes) and CD79 is essential for signaling. In addition, alternative transmembrane domain pairing between class II α and β chains influences association with membrane lipid sub-domains, impacting both signaling and antigen presentation. In contrast to the membrane-distal region of the class II molecule responsible for peptide binding and T-cell receptor engagement, the membrane-proximal region (composed of the connecting peptide, transmembrane domain, and cytoplasmic tail) mediates these “non-traditional” class II functions. Here, we review the literature on the function of the membrane-proximal region of the MHC class II molecule and discuss the impact of this aspect of class II immunobiology on immune regulation and human disease. PMID:27006762

The Immune Adaptor SLP-76 Binds to SUMO-RANGAP1 at Nuclear Pore Complex Filaments to Regulate Nuclear Import of Transcription Factors in T Cells

PubMed Central

Liu, Hebin; Schneider, Helga; Recino, Asha; Richardson, Christine; Goldberg, Martin W.; Rudd, Christopher E.

2015-01-01

Summary While immune cell adaptors regulate proximal T cell signaling, direct regulation of the nuclear pore complex (NPC) has not been reported. NPC has cytoplasmic filaments composed of RanGAP1 and RanBP2 with the potential to interact with cytoplasmic mediators. Here, we show that the immune cell adaptor SLP-76 binds directly to SUMO-RanGAP1 of cytoplasmic fibrils of the NPC, and that this interaction is needed for optimal NFATc1 and NF-κB p65 nuclear entry in T cells. Transmission electron microscopy showed anti-SLP-76 cytoplasmic labeling of the majority of NPCs in anti-CD3 activated T cells. Further, SUMO-RanGAP1 bound to the N-terminal lysine 56 of SLP-76 where the interaction was needed for optimal RanGAP1-NPC localization and GAP exchange activity. While the SLP-76-RanGAP1 (K56E) mutant had no effect on proximal signaling, it impaired NF-ATc1 and p65/RelA nuclear entry and in vivo responses to OVA peptide. Overall, we have identified SLP-76 as a direct regulator of nuclear pore function in T cells. PMID:26321253

The Immune Adaptor SLP-76 Binds to SUMO-RANGAP1 at Nuclear Pore Complex Filaments to Regulate Nuclear Import of Transcription Factors in T Cells.

PubMed

Liu, Hebin; Schneider, Helga; Recino, Asha; Richardson, Christine; Goldberg, Martin W; Rudd, Christopher E

2015-09-03

While immune cell adaptors regulate proximal T cell signaling, direct regulation of the nuclear pore complex (NPC) has not been reported. NPC has cytoplasmic filaments composed of RanGAP1 and RanBP2 with the potential to interact with cytoplasmic mediators. Here, we show that the immune cell adaptor SLP-76 binds directly to SUMO-RanGAP1 of cytoplasmic fibrils of the NPC, and that this interaction is needed for optimal NFATc1 and NF-κB p65 nuclear entry in T cells. Transmission electron microscopy showed anti-SLP-76 cytoplasmic labeling of the majority of NPCs in anti-CD3 activated T cells. Further, SUMO-RanGAP1 bound to the N-terminal lysine 56 of SLP-76 where the interaction was needed for optimal RanGAP1-NPC localization and GAP exchange activity. While the SLP-76-RanGAP1 (K56E) mutant had no effect on proximal signaling, it impaired NF-ATc1 and p65/RelA nuclear entry and in vivo responses to OVA peptide. Overall, we have identified SLP-76 as a direct regulator of nuclear pore function in T cells. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

A Bipartite Signal Regulates the Faithful Delivery of Apical Domain Marker Podocalyxin/Gp135

PubMed Central

Yu, Chun-Ying; Chen, Jen-Yau; Lin, Yu-Yu; Shen, Kuo-Fang; Lin, Wei-Ling; Chien, Chung-Liang; ter Beest, Martin B.A.

2007-01-01

Podocalyxin/Gp135 was recently demonstrated to participate in the formation of a preapical complex to set up initial polarity in MDCK cells, a function presumably depending on the apical targeting of Gp135. We show that correct apical sorting of Gp135 depends on a bipartite signal composed of an extracellular O-glycosylation–rich region and the intracellular PDZ domain–binding motif. The function of this PDZ-binding motif could be substituted with a fusion construct of Gp135 with Ezrin-binding phosphoprotein 50 (EBP50). In accordance with this observation, EBP50 binds to newly synthesized Gp135 at the Golgi apparatus and facilitates oligomerization and sorting of Gp135 into a clustering complex. A defective connection between Gp135 and EBP50 or EBP50 knockdown results in a delayed exit from the detergent-resistant microdomain, failure of oligomerization, and basolateral missorting of Gp135. Furthermore, the basolaterally missorted EBP50-binding defective mutant of Gp135 was rapidly retrieved via a PKC-dependent mechanism. According to these findings, we propose a model by which a highly negative charged transmembrane protein could be packed into an apical sorting platform with the aid of its cytoplasmic partner EBP50. PMID:17332505

Caveolae, caveolin-1 and cavin-1: Emerging roles in pulmonary hypertension.

PubMed

Chettimada, Sukrutha; Yang, Jincheng; Moon, Hyung-Geun; Jin, Yang

2015-07-28

Caveolae are flask-shaped invaginations of cell membrane that play a significant structural and functional role. Caveolae harbor a variety of signaling molecules and serve to receive, concentrate and transmit extracellular signals across the membrane. Caveolins are the main structural proteins residing in the caveolae. Caveolins and another category of newly identified caveolae regulatory proteins, named cavins, are not only responsible for caveolae formation, but also interact with signaling complexes in the caveolae and regulate transmission of signals across the membrane. In the lung, two of the three caveolin isoforms, i.e ., cav-1 and -2, are expressed ubiquitously. Cavin protein family is composed of four proteins, named cavin-1 (or PTRF for polymerase Ⅰ and transcript release factor), cavin-2 (or SDPR for serum deprivation protein response), cavin-3 (or SRBC for sdr-related gene product that binds to-c-kinase) and cavin-4 (or MURC for muscle restricted coiled-coiled protein or cavin-4). All the caveolin and cavin proteins are essential regulators for caveolae dynamics. Recently, emerging evidence suggest that caveolae and its associated proteins play crucial roles in development and progression of pulmonary hypertension. The focus of this review is to outline and discuss the contrast in alteration of cav-1 (cav-1),-2 and cavin-1 (PTRF) expression and downstream signaling mechanisms between human and experimental models of pulmonary hypertension.

Exploring the Multi-Layered Affordances of Composing and Performing Interactive Music with Responsive Technologies

PubMed Central

Einarsson, Anna; Ziemke, Tom

2017-01-01

The question motivating the work presented here, starting from a view of music as embodied and situated activity, is how can we account for the complexity of interactive music performance situations. These are situations in which human performers interact with responsive technologies, such as sensor-driven technology or sound synthesis affected by analysis of the performed sound signal. This requires investigating in detail the underlying mechanisms, but also providing a more holistic approach that does not lose track of the complex whole constituted by the interactions and relationships of composers, performers, audience, technologies, etc. The concept of affordances has frequently been invoked in musical research, which has seen a “bodily turn” in recent years, similar to the development of the embodied cognition approach in the cognitive sciences. We therefore begin by broadly delineating its usage in the cognitive sciences in general, and in music research in particular. We argue that what is still missing in the discourse on musical affordances is an encompassing theoretical framework incorporating the sociocultural dimensions that are fundamental to the situatedness and embodiment of interactive music performance and composition. We further argue that the cultural affordances framework, proposed by Rietveld and Kiverstein (2014) and recently articulated further by Ramstead et al. (2016) in this journal, although not previously applied to music, constitutes a promising starting point. It captures and elucidates this complex web of relationships in terms of shared landscapes and individual fields of affordances. We illustrate this with examples foremost from the first author's artistic work as composer and performer of interactive music. This sheds new light on musical composition as a process of construction—and embodied mental simulation—of situations, guiding the performers' and audience's attention in shifting fields of affordances. More generally, we believe that the theoretical perspectives and concrete examples discussed in this paper help to elucidate how situations—and with them affordances—are dynamically constructed through the interactions of various mechanisms as people engage in embodied and situated activity. PMID:29033880

An ATMND/SGI based label-free and fluorescence ratiometric aptasensor for rapid and highly sensitive detection of cocaine in biofluids.

PubMed

Wang, Jiamian; Song, Jie; Wang, Xiuyun; Wu, Shuo; Zhao, Yanqiu; Luo, Pinchen; Meng, Changgong

2016-12-01

A label-free ratiometric fluorescence aptasensor has been developed for the rapid and sensitive detection of cocaine in complex biofluids. The fluorescent aptasensor is composed of a non-labeled GC-38 cocaine aptamer which serves as a basic sensing unit and two fluorophores, 2-amino-5,6,7-trimethyl-1,8-naphthyridine (ATMND) and SYBR Green I (SGI) which serves as a signal reporter and a build-in reference, respectively. The detection principle is based on a specific cocaine mediated ATMND displacement reaction and the corresponding change in the fluorescence ratio of ATMND to SGI. Due to the high affinity of the non-labeled aptamer, the good precision originated from the ratiometric method, and the good fluorescence quantum yield of the fluorophore, the aptasensor shows good analytical performance with respect to cocaine detection. Under optimal conditions, the aptasensor shows a linear range of 0.10-10μM and a low limit of detection of 56nM, with a fast response of 20s. The low limit of detection is comparable to most of the fluorescent aptasensors with signal amplification strategies and much lower than all of the unamplified cocaine aptasensors. Practical sample analysis in a series of complex biofluids, including urine, saliva and serum, also indicates the good precision, stability, and high sensitivity of the aptasensor, which may have great potential for the point-of-care screening of cocaine in complex biofluids. Copyright © 2016 Elsevier B.V. All rights reserved.

The Adaptor Protein SAP Directly Associates with CD3ζ Chain and Regulates T Cell Receptor Signaling

PubMed Central

Proust, Richard; Bertoglio, Jacques; Gesbert, Franck

2012-01-01

Mutations altering the gene encoding the SLAM associated protein (SAP) are responsible for the X-linked lymphoproliferative disease or XLP1. Its absence is correlated with a defective NKT cells development, a decrease in B cell functions and a reduced T cells and NK cells cytotoxic activities, thus leading to an immunodeficiency syndrome. SAP is a small 128 amino-acid long protein that is almost exclusively composed of an SH2 domain. It has been shown to interact with the CD150/SLAM family of receptors, and in a non-canonical manner with SH3 containing proteins such as Fyn, βPIX, PKCθ and Nck1. It would thus play the role of a minimal adaptor protein. It has been shown that SAP plays an important function in the activation of T cells through its interaction with the SLAM family of receptors. Therefore SAP defective T cells display a reduced activation of signaling events downstream of the TCR-CD3 complex triggering. In the present work, we evidence that SAP is a direct interactor of the CD3ζ chain. This direct interaction occurs through the first ITAM of CD3ζ, proximal to the membrane. Additionally, we show that, in the context of the TCR-CD3 signaling, an Sh-RNA mediated silencing of SAP is responsible for a decrease of several canonical T cell signaling pathways including Erk, Akt and PLCγ1 and to a reduced induction of IL-2 and IL-4 mRNA. Altogether, we show that SAP plays a central function in the T cell activation processes through a direct association with the CD3 complex. PMID:22912825

Optimization of global model composed of radial basis functions using the term-ranking approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cai, Peng; Tao, Chao, E-mail: taochao@nju.edu.cn; Liu, Xiao-Jun

2014-03-15

A term-ranking method is put forward to optimize the global model composed of radial basis functions to improve the predictability of the model. The effectiveness of the proposed method is examined by numerical simulation and experimental data. Numerical simulations indicate that this method can significantly lengthen the prediction time and decrease the Bayesian information criterion of the model. The application to real voice signal shows that the optimized global model can capture more predictable component in chaos-like voice data and simultaneously reduce the predictable component (periodic pitch) in the residual signal.

[The Role of Calcium in the Conformational Changes of the Recombinant S100A8/S100A9].

PubMed

Gheibi, N; Asghari, H; Chegini, K G; Sahmani, M; Moghadasi, M

2016-01-01

Calprotectin is a member of the EF-hand proteins, composed of two subunits, S100A8 (MRP8) and S100A9 (MRP14). These proteins are involved in important processes including cell signaling, regulation of inflammatory responses, cell cycle control, differentiation, regulation of ion channel activity and defense against microbial agents in a calcium dependent manner. In the present study, recombinant S100A8 and S100A9 were expressed in E. coli BL21 and then purified using Ni-NTA affinity chromatography. The structure of the S100A8/A9 complex in the presence and absence of calcium was assessed by circular dichroism and fluorescence spectroscopy. The intrinsic fluorescence emission spectra of the S100A8/A9 complex in the presence of calcium showed a reduction in fluorescence intensity, reflecting conformational changes within the protein with the exposure of aromatic residues to the protein surface. The far ultraviolet-circular dichroism spectra of the complex in the presence of calcium revealed minor changes in the regular secondary structure of the complex. Also, increased thermal stability of the S100A8/A9 complex in the presence of calcium was indicated.

Inductive Interference in Rapid Transit Signaling Systems. Volume 1. Theory and Background.

DOT National Transportation Integrated Search

1986-05-01

This report describes the mechanism of inductive interference to audio frequency (AF) signaling systems used in rail transit operations, caused by rail transit vehicles with chopper propulsion control. Choppers are switching circuits composed of high...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rasmussen, Søren G.F.; DeVree, Brian T; Zou, Yaozhong

G protein-coupled receptors (GPCRs) are responsible for the majority of cellular responses to hormones and neurotransmitters as well as the senses of sight, olfaction and taste. The paradigm of GPCR signalling is the activation of a heterotrimeric GTP binding protein (G protein) by an agonist-occupied receptor. The β 2 adrenergic receptor (β 2AR) activation of Gs, the stimulatory G protein for adenylyl cyclase, has long been a model system for GPCR signalling. Here we present the crystal structure of the active state ternary complex composed of agonist-occupied monomeric β 2AR and nucleotide-free Gs heterotrimer. The principal interactions between the βmore » 2AR and Gs involve the amino- and carboxy-terminal α-helices of Gs, with conformational changes propagating to the nucleotide-binding pocket. The largest conformational changes in the β 2AR include a 14Å outward movement at the cytoplasmic end of transmembrane segment 6 (TM6) and an α-helical extension of the cytoplasmic end of TM5. The most surprising observation is a major displacement of the α-helical domain of Gαs relative to the Ras-like GTPase domain. This crystal structure represents the first high-resolution view of transmembrane signalling by a GPCR.« less

Target-in-the-loop remote sensing of laser beam and atmospheric turbulence characteristics.

PubMed

Vorontsov, Mikhail A; Lachinova, Svetlana L; Majumdar, Arun K

2016-07-01

A new target-in-the-loop (TIL) atmospheric sensing concept for in situ remote measurements of major laser beam characteristics and atmospheric turbulence parameters is proposed and analyzed numerically. The technique is based on utilization of an integral relationship between complex amplitudes of the counterpropagating optical waves known as overlapping integral or interference metric, whose value is preserved along the propagation path. It is shown that the interference metric can be directly measured using the proposed TIL sensing system composed of a single-mode fiber-based optical transceiver and a remotely located retro-target. The measured signal allows retrieval of key beam and atmospheric turbulence characteristics including scintillation index and the path-integrated refractive index structure parameter.

Spatial and temporal coherence in perceptual binding

PubMed Central

Blake, Randolph; Yang, Yuede

1997-01-01

Component visual features of objects are registered by distributed patterns of activity among neurons comprising multiple pathways and visual areas. How these distributed patterns of activity give rise to unified representations of objects remains unresolved, although one recent, controversial view posits temporal coherence of neural activity as a binding agent. Motivated by the possible role of temporal coherence in feature binding, we devised a novel psychophysical task that requires the detection of temporal coherence among features comprising complex visual images. Results show that human observers can more easily detect synchronized patterns of temporal contrast modulation within hybrid visual images composed of two components when those components are drawn from the same original picture. Evidently, time-varying changes within spatially coherent features produce more salient neural signals. PMID:9192701

Limits of Kirchhoff's Laws in Plasmonics.

PubMed

Razinskas, Gary; Biagioni, Paolo; Hecht, Bert

2018-01-30

The validity of Kirchhoff's laws in plasmonic nanocircuitry is investigated by studying a junction of plasmonic two-wire transmission lines. We find that Kirchhoff's laws are valid for sufficiently small values of a phenomenological parameter κ relating the geometrical parameters of the transmission line with the effective wavelength of the guided mode. Beyond such regime, for large values of the phenomenological parameter, increasing deviations occur and the equivalent impedance description (Kirchhoff's laws) can only provide rough, but nevertheless useful, guidelines for the design of more complex plasmonic circuitry. As an example we investigate a system composed of a two-wire transmission line and a nanoantenna as the load. By addition of a parallel stub designed according to Kirchhoff's laws we achieve maximum signal transfer to the nanoantenna.

A flame burning within.

PubMed

Ferrucci, Luigi; Ble, Alessandro; Bandinelli, Stefania; Lauretani, Fulvio; Suthers, Kristen; Guralnik, Jack M

2004-06-01

Inflammation is a human being's primary defense against threats to homeostasis that are encountered every day. Especially in old age, when regulatory mechanisms responsible for inflammatory responses may be ineffective or damaged, the result can be adverse pathological conditions, and an increased risk of morbidity and mortality. The inflammation response is a plastic network composed of redundant signaling among several different mediators. These mediators have a reciprocal relationship with other biological sub-systems, including hormone regulation, the autonomic nervous system, and oxidative/anti-oxidant balance. Studying this complex architecture requires parallel and multiple research strategies from epidemiological to biochemical level, from observational studies to innovative intervention approaches. Given that the inflammatory response is a critical age-related process, understanding its regulatory action is essential in avoiding hazardous consequences in old age.

[Germ cell membrane lipids in spermatogenesis].

PubMed

Wang, Ting; Shi, Xiao; Quan, Song

2016-05-01

Spermatogenesis is a complex developmental process in which a diploid progenitor germ cell transforms into highly specialized spermatozoa. During spermatogenesis, membrane remodeling takes place, and cell membrane permeability and liquidity undergo phase-specific changes, which are all associated with the alteration of membrane lipids. Lipids are important components of the germ cell membrane, whose volume and ratio fluctuate in different phases of spermatogenesis. Abnormal lipid metabolism can cause spermatogenic dysfunction and consequently male infertility. Germ cell membrane lipids are mainly composed of cholesterol, phospholipids and glycolipids, which play critical roles in cell adhesion and signal transduction during spermatogenesis. An insight into the correlation of membrane lipids with spermatogenesis helps us to better understand the mechanisms of spermatogenesis and provide new approaches to the diagnosis and treatment of male infertility.

"And Now That I Know Them": Composing Mutuality in a Service Learning Course.

ERIC Educational Resources Information Center

Welch, Nancy

2002-01-01

Turns to contemporary feminist object-relations theory to understand the efforts of students in a service learning course, to push beyond the usual subject-object, active-passive dualisms that pervade community-based literacy projects, and to compose instead complex representations in which all participants are composed as active, as knowing, and…

A three-dimensional microelectrode array composed of vertically aligned ultra-dense carbon nanotube networks

NASA Astrophysics Data System (ADS)

Nick, C.; Yadav, S.; Joshi, R.; Schneider, J. J.; Thielemann, C.

2015-07-01

Electrodes based on carbon nanotubes are a promising approach to manufacture highly sensitive sensors with a low limit of signal detection and a high signal-to-noise ratio. This is achieved by dramatically increasing the electrochemical active surface area without increasing the overall geometrical dimensions. Typically, carbon nanotube electrodes are nearly planar and composed of randomly distributed carbon nanotube networks having a limited surface gain for a specific geometrical surface area. To overcome this limitation, we have introduced vertically aligned carbon nanotube (VACNT) networks as electrodes, which are arranged in a microelectrode pattern of 60 single electrodes. Each microelectrode features a very high aspect ratio of more than 300 and thus a dramatically increased surface area. These microelectrodes composed of VACNT networks display dramatically decreased impedance over the entire frequency range compared to planar microelectrodes caused by the enormous capacity increase. This is experimentally verified by electrochemical impedance spectroscopy and cyclic voltammetry.

Programming molecular self-assembly of intrinsically disordered proteins containing sequences of low complexity

NASA Astrophysics Data System (ADS)

Simon, Joseph R.; Carroll, Nick J.; Rubinstein, Michael; Chilkoti, Ashutosh; López, Gabriel P.

2017-06-01

Dynamic protein-rich intracellular structures that contain phase-separated intrinsically disordered proteins (IDPs) composed of sequences of low complexity (SLC) have been shown to serve a variety of important cellular functions, which include signalling, compartmentalization and stabilization. However, our understanding of these structures and our ability to synthesize models of them have been limited. We present design rules for IDPs possessing SLCs that phase separate into diverse assemblies within droplet microenvironments. Using theoretical analyses, we interpret the phase behaviour of archetypal IDP sequences and demonstrate the rational design of a vast library of multicomponent protein-rich structures that ranges from uniform nano-, meso- and microscale puncta (distinct protein droplets) to multilayered orthogonally phase-separated granular structures. The ability to predict and program IDP-rich assemblies in this fashion offers new insights into (1) genetic-to-molecular-to-macroscale relationships that encode hierarchical IDP assemblies, (2) design rules of such assemblies in cell biology and (3) molecular-level engineering of self-assembled recombinant IDP-rich materials.

γ-Tubulin complex in Trypanosoma brucei: molecular composition, subunit interdependence and requirement for axonemal central pair protein assembly.

PubMed

Zhou, Qing; Li, Ziyin

2015-11-01

γ-Tubulin complex constitutes a key component of the microtubule-organizing center and nucleates microtubule assembly. This complex differs in complexity in different organisms: the budding yeast contains the γ-tubulin small complex (γTuSC) composed of γ-tubulin, gamma-tubulin complex protein (GCP)2 and GCP3, whereas animals contain the γ-tubulin ring complex (γTuRC) composed of γTuSC and three additional proteins, GCP4, GCP5 and GCP6. In Trypanosoma brucei, the composition of the γ-tubulin complex remains elusive, and it is not known whether it also regulates assembly of the subpellicular microtubules and the spindle microtubules. Here we report that the γ-tubulin complex in T. brucei is composed of γ-tubulin and three GCP proteins, GCP2-GCP4, and is primarily localized in the basal body throughout the cell cycle. Depletion of GCP2 and GCP3, but not GCP4, disrupted the axonemal central pair microtubules, but not the subpellicular microtubules and the spindle microtubules. Furthermore, we showed that the γTuSC is required for assembly of two central pair proteins and that γTuSC subunits are mutually required for stability. Together, these results identified an unusual γ-tubulin complex in T. brucei, uncovered an essential role of γTuSC in central pair protein assembly, and demonstrated the interdependence of individual γTuSC components for maintaining a stable complex. © 2015 John Wiley & Sons Ltd.

The principles of collective animal behaviour

PubMed Central

Sumpter, D.J.T

2005-01-01

In recent years, the concept of self-organization has been used to understand collective behaviour of animals. The central tenet of self-organization is that simple repeated interactions between individuals can produce complex adaptive patterns at the level of the group. Inspiration comes from patterns seen in physical systems, such as spiralling chemical waves, which arise without complexity at the level of the individual units of which the system is composed. The suggestion is that biological structures such as termite mounds, ant trail networks and even human crowds can be explained in terms of repeated interactions between the animals and their environment, without invoking individual complexity. Here, I review cases in which the self-organization approach has been successful in explaining collective behaviour of animal groups and societies. Ant pheromone trail networks, aggregation of cockroaches, the applause of opera audiences and the migration of fish schools have all been accurately described in terms of individuals following simple sets of rules. Unlike the simple units composing physical systems, however, animals are themselves complex entities, and other examples of collective behaviour, such as honey bee foraging with its myriad of dance signals and behavioural cues, cannot be fully understood in terms of simple individuals alone. I argue that the key to understanding collective behaviour lies in identifying the principles of the behavioural algorithms followed by individual animals and of how information flows between the animals. These principles, such as positive feedback, response thresholds and individual integrity, are repeatedly observed in very different animal societies. The future of collective behaviour research lies in classifying these principles, establishing the properties they produce at a group level and asking why they have evolved in so many different and distinct natural systems. Ultimately, this research could inform not only our understanding of animal societies, but also the principles by which we organize our own society. PMID:16553306

The principles of collective animal behaviour.

PubMed

Sumpter, D J T

2006-01-29

In recent years, the concept of self-organization has been used to understand collective behaviour of animals. The central tenet of self-organization is that simple repeated interactions between individuals can produce complex adaptive patterns at the level of the group. Inspiration comes from patterns seen in physical systems, such as spiralling chemical waves, which arise without complexity at the level of the individual units of which the system is composed. The suggestion is that biological structures such as termite mounds, ant trail networks and even human crowds can be explained in terms of repeated interactions between the animals and their environment, without invoking individual complexity. Here, I review cases in which the self-organization approach has been successful in explaining collective behaviour of animal groups and societies. Ant pheromone trail networks, aggregation of cockroaches, the applause of opera audiences and the migration of fish schools have all been accurately described in terms of individuals following simple sets of rules. Unlike the simple units composing physical systems, however, animals are themselves complex entities, and other examples of collective behaviour, such as honey bee foraging with its myriad of dance signals and behavioural cues, cannot be fully understood in terms of simple individuals alone. I argue that the key to understanding collective behaviour lies in identifying the principles of the behavioural algorithms followed by individual animals and of how information flows between the animals. These principles, such as positive feedback, response thresholds and individual integrity, are repeatedly observed in very different animal societies. The future of collective behaviour research lies in classifying these principles, establishing the properties they produce at a group level and asking why they have evolved in so many different and distinct natural systems. Ultimately, this research could inform not only our understanding of animal societies, but also the principles by which we organize our own society.

Multiscale Modeling of Cardiac Cellular Energetics

PubMed Central

BASSINGTHWAIGHTE, JAMES B.; CHIZECK, HOWARD J.; ATLAS, LES E.; QIAN, HONG

2010-01-01

Multiscale modeling is essential to integrating knowledge of human physiology starting from genomics, molecular biology, and the environment through the levels of cells, tissues, and organs all the way to integrated systems behavior. The lowest levels concern biophysical and biochemical events. The higher levels of organization in tissues, organs, and organism are complex, representing the dynamically varying behavior of billions of cells interacting together. Models integrating cellular events into tissue and organ behavior are forced to resort to simplifications to minimize computational complexity, thus reducing the model’s ability to respond correctly to dynamic changes in external conditions. Adjustments at protein and gene regulatory levels shortchange the simplified higher-level representations. Our cell primitive is composed of a set of subcellular modules, each defining an intracellular function (action potential, tricarboxylic acid cycle, oxidative phosphorylation, glycolysis, calcium cycling, contraction, etc.), composing what we call the “eternal cell,” which assumes that there is neither proteolysis nor protein synthesis. Within the modules are elements describing each particular component (i.e., enzymatic reactions of assorted types, transporters, ionic channels, binding sites, etc.). Cell subregions are stirred tanks, linked by diffusional or transporter-mediated exchange. The modeling uses ordinary differential equations rather than stochastic or partial differential equations. This basic model is regarded as a primitive upon which to build models encompassing gene regulation, signaling, and long-term adaptations in structure and function. During simulation, simpler forms of the model are used, when possible, to reduce computation. However, when this results in error, the more complex and detailed modules and elements need to be employed to improve model realism. The processes of error recognition and of mapping between different levels of model form complexity are challenging but are essential for successful modeling of large-scale systems in reasonable time. Currently there is to this end no established methodology from computational sciences. PMID:16093514

On Integration and Validation of a Very Low Complexity ATC UWB System for Muscle Force Transmission.

PubMed

Sapienza, Stefano; Crepaldi, Marco; Motto Ros, Paolo; Bonanno, Alberto; Demarchi, Danilo

2016-04-01

The thresholding of Surface ElectroMyoGraphic (sEMG) signals, i.e., Average Threshold Crossing (ATC) technique, reduces the amount of data to be processed enabling circuit complexity reduction and low power consumption. This paper investigates the lowest level of complexity reachable by an ATC system through measurements and in-vivo experiments with an embedded prototype for wireless force transmission, based on asynchronous Impulse-Radio Ultra Wide Band (IR-UWB). The prototype is composed by the acquisition unit, a wearable PCB 23 × 34 mm, which includes a full custom IC integrating a UWB transmitter (chip active silicon area 0.016 mm(2), 1 mW power consumption), and the receiver. The system is completely asynchronous, it acquires a differential sEMG signal, generates the ATC events and triggers a 3.3 GHz IR-UWB transmission. ATC robustness relaxes filters constraints: two passive first order filters have been implemented, bandwidth from 10 Hz up to 1 kHz. Energy needed for the single pulse generation is 30 pJ while the whole PCB consumes 5.65 mW. The pulses radiated by the acquisition unit TX are received by a short-range and low complexity threshold-based 130 nm CMOS IR-UWB receiver with an Ultra Low Power (ULP) baseband unit capable of robustly receiving generic quasi-digital pulse sequences. The acquisition unit have been tested with 10 series of in vivo isometric and isotonic contractions, while the transmission channel with over-the-air and cable measurements obtained with a couple of planar monopole antennas and an integrated 0.004 mm(2) transmitter, the same used for the acquisition unit, with realistic channel conditions. The entire system, acquisition unit and receiver, consumes 15.49 mW.

Sensitive detection of microRNA in complex biological samples by using two stages DSN-assisted target recycling signal amplification method.

PubMed

Zhang, Kai; Wang, Ke; Zhu, Xue; Xu, Fei; Xie, Minhao

2017-01-15

MicroRNA (miRNA) has become an important biomarker candidate for cancer diagnosis, prognosis, and therapy. In this study, we have developed a novel fluorescence method for sensitive and specific miRNA detection via duplex specific nuclease (DSN) signal amplification and demonstrated its practical application in biological samples. Malachite green (MG) was employed as a "label-free" signal transducer since fluorescence of MG could be enhanced by 100-fold when MG were binding to a G-quadruplex structure formed within the d(G 2 T) 13 G sequence. The proposed signal amplification strategy is an integrated "biological circuit" designed to initiate a cascade of enzymatic reactions in order to detect, amplify, and measure a specific miRNA sequence by using the isothermal cleavage property of a DSN. The circuit is composed of two molecular switches operating in series: the amplification reaction activated by a specific miRNA and the strand-displacement polymerization reaction designed to initiate molecular beacon-assisted amplification and signal transduction by using MG/G-quadruplex complex. The hsa-miR-141 (miR141) was chosen as a target miRNA because its level specifically abnormal in a wide range of common human cancers including breast, lung, colon, and prostate cancer. The proposed method allowed quantitative sequence-specific detection of miR141 (with a detection limit of 1.03pM) in a dynamic range from 1pM to 10μM, with an excellent ability to discriminate differences in miRNAs. Moreover, the detection assay was applied to quantify miR141 in cancerous cell lysates. On the basis of these findings, we believe that this proposed sensitive and specific assay has great potential as a miRNA quantification method for use in biomedical research and clinical diagnosis. Copyright © 2016 Elsevier B.V. All rights reserved.

The γ-tubulin complex in Trypanosoma brucei: molecular composition, subunit interdependence and requirement for axonemal central pair protein assembly

PubMed Central

Zhou, Qing; Li, Ziyin

2015-01-01

The γ-tubulin complex constitutes a key component of the microtubule-organizing center and nucleates microtubule assembly. This complex differs in complexity in different organisms: the budding yeast contains the γ-tubulin small complex (γTuSC) composed of γ-tubulin, GCP2 and GCP3, whereas animals contain the γ-tubulin ring complex (γTuRC) composed of γTuSC and three additional proteins, GCP4, GCP5 and GCP6. In Trypanosoma brucei, the composition of the γ-tubulin complex remains elusive, and it is not known whether it also regulates assembly of the subpellicular microtubules and the spindle microtubules. Here we report that the γ-tubulin complex in T. brucei is composed of γ-tubulin and three GCP proteins, GCP2-GCP4, and is primarily localized in the basal body throughout the cell cycle. Depletion of GCP2 and GCP3, but not GCP4, disrupted the axonemal central pair microtubules, but not the subpellicular microtubules and the spindle microtubules. Furthermore, we showed that the γTuSC is required for assembly of two central pair proteins and that γTuSC subunits are mutually required for stability. Together, these results identified an unusual γ-tubulin complex in T. brucei, uncovered an essential role of γTuSC in central pair protein assembly, and demonstrated the interdependence of individual γTuSC components for maintaining a stable complex. PMID:26224545

Ligand-Induced Energy Shift and Localization of Kondo Resonances in Cobalt-Based Complexes on Cu(111).

PubMed

Knaak, Thomas; Gruber, Manuel; Lindström, Christoph; Bocquet, Marie-Laure; Heck, Jürgen; Berndt, Richard

2017-11-08

Magnetic sandwich complexes are of particular interest for molecular spintronics. Using scanning tunneling microscopy, we evidence the successful deposition of 1,3,5-tris(η 6 -borabenzene-η 5 -cyclopentadienylcobalt) benzene, a molecule composed of three connected magnetic sandwich units, on Cu(111). Scanning tunneling spectra reveal two distinct spatial-dependent narrow resonances close to the Fermi level for the trimer molecules as well as for molecular fragments composed of one and two magnetic units. With the help of density functional theory, these resonances are interpreted as two Kondo resonances originating from two distinct nondegenerate d-like orbitals. These Kondo resonances are found to have defined spatial extents dictated by the hybridization of the involved orbitals with that of the ligands. These results opens promising perspectives for investigating complex Kondo systems composed of several "Kondo" orbitals.

Complexity Leadership: A Theoretical Perspective

ERIC Educational Resources Information Center

Baltaci, Ali; Balci, Ali

2017-01-01

Complex systems are social networks composed of interactive employees interconnected through collaborative, dynamic ties such as shared goals, perspectives and needs. Complex systems are largely based on "the complex system theory". The complex system theory focuses mainly on finding out and developing strategies and behaviours that…

Corti's organ physiology-based cochlear model: a microelectronic prosthetic implant

NASA Astrophysics Data System (ADS)

Rios, Francisco; Fernandez-Ramos, Raquel; Romero-Sanchez, Jorge; Martin, Jose Francisco

2003-04-01

Corti"s Organ is an Electro-Mechanical transducer that allows the energy coupling between acoustical stimuli and auditory nerve. Although the structure and funtionality of this organ are complex, state of the art models have been currently developed and tested. Cochlea model presented in this paper is based on the theories of Bekesy and others and concerns on the behaviour of auditory system on frequency-place domain and mechanisms of lateral inhibition. At the same time, present state of technology will permit us developing a microsystem that reproduce this phenomena applied to hearing aid prosthesis. Corti"s Organ is composed of more than 20.000 cilia excited by mean of travelling waves. These waves produce relative pressures distributed along the cochlea, exciting an specific number of cilia in a local way. Nonlinear mechanisms of local adaptation to the intensity (external cilia cells) and lateral inhibition (internal cilia cells) allow the selection of very few elements excited. These transmit a very precise intensity and frequency information. These signals are the only ones coupled to the auditory nerve. Distribution of pressure waves matches a quasilogaritmic law due to Cochlea morphology. Microsystem presented in this paper takes Bark"s law as an approximation to this behaviour consisting on grouped arbitrary elements composed of a set of selective coupled exciters (bank of filters according to Patterson"s model).These sets apply the intensity adaptation principles and lateral inhibition. Elements excited during the process generate a bioelectric signal in the same way than cilia cell. A microelectronic solution is presented for the development of an implantable prosthesis device.

Sound Richness of Music Might Be Mediated by Color Perception: A PET Study.

PubMed

Satoh, Masayuki; Nagata, Ken; Tomimoto, Hidekazu

2015-01-01

We investigated the role of the fusiform cortex in music processing with the use of PET, focusing on the perception of sound richness. Musically naïve subjects listened to familiar melodies with three kinds of accompaniments: (i) an accompaniment composed of only three basic chords (chord condition), (ii) a simple accompaniment typically used in traditional music text books in elementary school (simple condition), and (iii) an accompaniment with rich and flowery sounds composed by a professional composer (complex condition). Using a PET subtraction technique, we studied changes in regional cerebral blood flow (rCBF) in simple minus chord, complex minus simple, and complex minus chord conditions. The simple minus chord, complex minus simple, and complex minus chord conditions regularly showed increases in rCBF at the posterior portion of the inferior temporal gyrus, including the LOC and fusiform gyrus. We may conclude that certain association cortices such as the LOC and the fusiform cortex may represent centers of multisensory integration, with foreground and background segregation occurring at the LOC level and the recognition of richness and floweriness of stimuli occurring in the fusiform cortex, both in terms of vision and audition.

Deconstructing the core dynamics from a complex time-lagged regulatory biological circuit.

PubMed

Eriksson, O; Brinne, B; Zhou, Y; Björkegren, J; Tegnér, J

2009-03-01

Complex regulatory dynamics is ubiquitous in molecular networks composed of genes and proteins. Recent progress in computational biology and its application to molecular data generate a growing number of complex networks. Yet, it has been difficult to understand the governing principles of these networks beyond graphical analysis or extensive numerical simulations. Here the authors exploit several simplifying biological circumstances which thereby enable to directly detect the underlying dynamical regularities driving periodic oscillations in a dynamical nonlinear computational model of a protein-protein network. System analysis is performed using the cell cycle, a mathematically well-described complex regulatory circuit driven by external signals. By introducing an explicit time delay and using a 'tearing-and-zooming' approach the authors reduce the system to a piecewise linear system with two variables that capture the dynamics of this complex network. A key step in the analysis is the identification of functional subsystems by identifying the relations between state-variables within the model. These functional subsystems are referred to as dynamical modules operating as sensitive switches in the original complex model. By using reduced mathematical representations of the subsystems the authors derive explicit conditions on how the cell cycle dynamics depends on system parameters, and can, for the first time, analyse and prove global conditions for system stability. The approach which includes utilising biological simplifying conditions, identification of dynamical modules and mathematical reduction of the model complexity may be applicable to other well-characterised biological regulatory circuits. [Includes supplementary material].

Fluctuations of pol I and fibrillarin contents of the nucleoli.

PubMed

Hornáček, M; Kováčik, L; Mazel, T; Cmarko, D; Bártová, E; Raška, I; Smirnov, E

2017-07-04

Nucleoli are formed on the basis of ribosomal DNA (rDNA) clusters called Nucleolus Organizer Regions (NORs). Each NOR contains multiple genes coding for RNAs of the ribosomal particles. The prominent components of the nucleolar ultrastructure, fibrillar centers (FC) and dense fibrillar components (DFC), together compose FC/DFC units. These units are centers of rDNA transcription by RNA polymerase I (pol I), as well as the early processing events, in which an essential role belongs to fibrillarin. Each FC/DFC unit probably corresponds to a single transcriptionally active gene. In this work, we transfected human-derived cells with GFP-RPA43 (subunit of pol I) and RFP-fibrillarin. Following changes of the fluorescent signals in individual FC/DFC units, we found two kinds of kinetics: 1) the rapid fluctuations with periods of 2-3 min, when the pol I and fibrillarin signals oscillated in anti-phase manner, and the intensities of pol I in the neighboring FC/DFC units did not correlate. 2) fluctuations with periods of 10 to 60 min, in which pol I and fibrillarin signals measured in the same unit did not correlate, but pol I signals in the units belonging to different nucleoli were synchronized. Our data indicate that a complex pulsing activity of transcription as well as early processing is common for ribosomal genes.

Detection of structural damage in multiwire cables by monitoring the entropy evolution of wavelet coefficients

NASA Astrophysics Data System (ADS)

Ibáñez, Flor; Baltazar, Arturo; Mijarez, Rito; Aranda, Jorge

2015-03-01

Multiwire cables are widely used in important civil structures. Since they are exposed to several dynamic and static loads, their structural health can be compromised. The cables can also be submitted to mechanical contact, tension and energy propagation in addition to changes in size and material within their wires. Due to the critical role played by multiwire cables, it is necessary to develop a non-destructive health monitoring method to maintain their structure and proper performance. Ultrasonic inspection using guided waves is a promising non-destructive damage monitoring technique for rods, single wires and multiwire cables. The propagated guided waves are composed by an infinite number of vibrational modes making their analysis difficult. In this work, an entropy-based method to identify small changes in non-stationary signals is proposed. A system to capture and post-process acoustic signals is implemented. The Discrete Wavelet Transform (DWT) is computed in order to obtain the reconstructed wavelet coefficients of the signals and to analyze the energy at different scales. The feasibility of using the concept of entropy evolution of non-stationary signals to detect damage in multiwire cables is evaluated. The results show that there is a high correlation between the entropy value and damage level of the cable. The proposed method has low sensitivity to noise and reduces the computational complexity found in a typical time-frequency analysis.

Response to Hyperosmotic Stress

PubMed Central

Saito, Haruo; Posas, Francesc

2012-01-01

An appropriate response and adaptation to hyperosmolarity, i.e., an external osmolarity that is higher than the physiological range, can be a matter of life or death for all cells. It is especially important for free-living organisms such as the yeast Saccharomyces cerevisiae. When exposed to hyperosmotic stress, the yeast initiates a complex adaptive program that includes temporary arrest of cell-cycle progression, adjustment of transcription and translation patterns, and the synthesis and retention of the compatible osmolyte glycerol. These adaptive responses are mostly governed by the high osmolarity glycerol (HOG) pathway, which is composed of membrane-associated osmosensors, an intracellular signaling pathway whose core is the Hog1 MAP kinase (MAPK) cascade, and cytoplasmic and nuclear effector functions. The entire pathway is conserved in diverse fungal species, while the Hog1 MAPK cascade is conserved even in higher eukaryotes including humans. This conservation is illustrated by the fact that the mammalian stress-responsive p38 MAPK can rescue the osmosensitivity of hog1Δ mutations in response to hyperosmotic challenge. As the HOG pathway is one of the best-understood eukaryotic signal transduction pathways, it is useful not only as a model for analysis of osmostress responses, but also as a model for mathematical analysis of signal transduction pathways. In this review, we have summarized the current understanding of both the upstream signaling mechanism and the downstream adaptive responses to hyperosmotic stress in yeast. PMID:23028184

Rate-distortion optimized tree-structured compression algorithms for piecewise polynomial images.

PubMed

Shukla, Rahul; Dragotti, Pier Luigi; Do, Minh N; Vetterli, Martin

2005-03-01

This paper presents novel coding algorithms based on tree-structured segmentation, which achieve the correct asymptotic rate-distortion (R-D) behavior for a simple class of signals, known as piecewise polynomials, by using an R-D based prune and join scheme. For the one-dimensional case, our scheme is based on binary-tree segmentation of the signal. This scheme approximates the signal segments using polynomial models and utilizes an R-D optimal bit allocation strategy among the different signal segments. The scheme further encodes similar neighbors jointly to achieve the correct exponentially decaying R-D behavior (D(R) - c(o)2(-c1R)), thus improving over classic wavelet schemes. We also prove that the computational complexity of the scheme is of O(N log N). We then show the extension of this scheme to the two-dimensional case using a quadtree. This quadtree-coding scheme also achieves an exponentially decaying R-D behavior, for the polygonal image model composed of a white polygon-shaped object against a uniform black background, with low computational cost of O(N log N). Again, the key is an R-D optimized prune and join strategy. Finally, we conclude with numerical results, which show that the proposed quadtree-coding scheme outperforms JPEG2000 by about 1 dB for real images, like cameraman, at low rates of around 0.15 bpp.

A chemotactic signaling surface on CheY defined by suppressors of flagellar switch mutations.

PubMed Central

Roman, S J; Meyers, M; Volz, K; Matsumura, P

1992-01-01

CheY is the response regulator protein that interacts with the flagellar switch apparatus to modulate flagellar rotation during chemotactic signaling. CheY can be phosphorylated and dephosphorylated in vitro, and evidence indicates that CheY-P is the activated form that induces clockwise flagellar rotation, resulting in a tumble in the cell's swimming pattern. The flagellar switch apparatus is a complex macromolecular structure composed of at least three gene products, FliG, FliM, and FliN. Genetic analysis of Escherichia coli has identified fliG and fliM as genes in which mutations occur that allele specifically suppress cheY mutations, indicating interactions among these gene products. We have generated a class of cheY mutations selected for dominant suppression of fliG mutations. Interestingly, these cheY mutations dominantly suppressed both fliG and fliM mutations; this is consistent with the idea that the CheY protein interacts with both switch gene products during signaling. Biochemical characterization of wild-type and suppressor CheY proteins did not reveal altered phosphorylation properties or evidence for phosphorylation-dependent CheY multimerization. These data indicate that suppressor CheY proteins are specifically altered in the ability to transduce chemotactic signals to the switch at some point subsequent to phosphorylation. Physical mapping of suppressor amino acid substitutions on the crystal structure of CheY revealed a high degree of spatial clustering, suggesting that this region of CheY is a signaling surface that transduces chemotactic signals to the switch. Images PMID:1400175

STS-2 - SOFTWARE INTEGRATION TESTS (SIT) - KSC

NASA Image and Video Library

1981-09-01

S81-36331 (24 Aug. 1981) --- Astronauts Joe H. Engle, left, and Richard H. Truly pause before participating in the integrated test of the assembled space shuttle components scheduled for launch no earlier than Sept. 30, 1981. Moments later, Engle, STS-2 crew commander, and Truly, pilot, entered the cabin of the orbiter Columbia for a mission simulation. The shuttle integrated tests (SIT) are designed to check out every connection and signal path in the STS-2 vehicle composed of the orbiter, two solid rocket boosters (SRB) and an external fuel tank (ET) for Columbia?s main engines. Completion of the tests will clear the way for preparations for rollout to Pad A at Launch Complex 39, scheduled for the latter part of August or early September. Photo credit: NASA

Propulsion System with Pneumatic Artificial Muscles for Powering Ankle-Foot Orthosis

NASA Astrophysics Data System (ADS)

Veneva, Ivanka; Vanderborght, Bram; Lefeber, Dirk; Cherelle, Pierre

2013-12-01

The aim of this paper is to present the design of device for control of new propulsion system with pneumatic artificial muscles. The propulsion system can be used for ankle joint articulation, for assisting and rehabilitation in cases of injured ankle-foot complex, stroke patients or elderly with functional weakness. Proposed device for control is composed by microcontroller, generator for muscles contractions and sensor system. The microcontroller receives the control signals from sensors and modulates ankle joint flex- ion and extension during human motion. The local joint control with a PID (Proportional-Integral Derivative) position feedback directly calculates desired pressure levels and dictates the necessary contractions. The main goal is to achieve an adaptation of the system and provide the necessary joint torque using position control with feedback.

The neuronal porosome complex in health and disease

PubMed Central

Naik, Akshata R; Lewis, Kenneth T

2015-01-01

Cup-shaped secretory portals at the cell plasma membrane called porosomes mediate the precision release of intravesicular material from cells. Membrane-bound secretory vesicles transiently dock and fuse at the base of porosomes facing the cytosol to expel pressurized intravesicular contents from the cell during secretion. The structure, isolation, composition, and functional reconstitution of the neuronal porosome complex have greatly progressed, providing a molecular understanding of its function in health and disease. Neuronal porosomes are 15 nm cup-shaped lipoprotein structures composed of nearly 40 proteins, compared to the 120 nm nuclear pore complex composed of >500 protein molecules. Membrane proteins compose the porosome complex, making it practically impossible to solve its atomic structure. However, atomic force microscopy and small-angle X-ray solution scattering studies have provided three-dimensional structural details of the native neuronal porosome at sub-nanometer resolution, providing insights into the molecular mechanism of its function. The participation of several porosome proteins previously implicated in neurotransmission and neurological disorders, further attest to the crosstalk between porosome proteins and their coordinated involvement in release of neurotransmitter at the synapse. PMID:26264442

Charge transfer complexes of metal-free phthalocyanine radical anions with decamethylmetallocenium cations: (Cp*2Co+)(H2Pc˙-)·solvent and (Cp*2Cr+)(H2Pc˙-)·4C6H4Cl2.

PubMed

Konarev, Dmitri V; Khasanov, Salavat S; Ishikawa, Manabu; Otsuka, Akihiro; Yamochi, Hideki; Saito, Gunzi; Lyubovskaya, Rimma N

2017-03-14

Charge transfer complexes (Cp* 2 Co + )(H 2 Pc˙ - )·0.5C 6 H 4 Cl 2 ·0.7C 6 H 5 CN·0.3C 6 H 14 (1) and (Cp* 2 Cr + )(H 2 Pc˙ - )·4C 6 H 4 Cl 2 (2) have been obtained as single crystals. Both complexes contain metal-free phthalocyanine (Pc) radical anions and decamethylmetallocenium cations. Reduction of the Pc macrocycle leads to the appearance of new bands at 1026-1030 nm in the NIR range and blue shifts of both Soret and Q-bands of H 2 Pc in the spectra of 1 and 2. The geometry of the Pc macrocycles supports the formation of H 2 Pc˙ - by the alternation of shorter and longer C-N(imine) bonds in the macrocycles in 2. Complex 1 contains pairs of H 2 Pc˙ - having effective π-π interactions with two sandwiched Cp* 2 Co + cations, whereas complex 2 contains stacks composed of alternating Cp* 2 Cr + and H 2 Pc˙ - ions. The magnetic moment of 1 is 1.64 μ B at 300 K due to the contribution of the H 2 Pc˙ - spins with the S = 1/2 state and diamagnetism of Cp* 2 Co + . This is supported by the observation of a narrow EPR signal of 1 with g = 2.0032-2.0036 characteristic of H 2 Pc˙ - . Strong antiferromagnetic coupling of spins with a Weiss temperature of -23 K is observed between H 2 Pc˙ - in 1. This coupling is probably mediated by the Cp* 2 Co + cations. The magnetic moment of 2 is 4.18 μ B at 300 K indicating the contribution of both paramagnetic H 2 Pc˙ - (S = 1/2) and Cp* 2 Cr + (S = 3/2) species. In spite of the presence of stacks of alternating ions in 2, only weak magnetic coupling is observed with a Weiss temperature of -4 K most probably due to ineffective π-π interactions between Cp* 2 Cr + and H 2 Pc˙ - . The EPR spectrum of 2 contains an asymmetric signal attributed to Cr III (g 1 = 3.9059-3.9220) and a narrow Lorentzian signal from H 2 Pc˙ - with g 2 = 1.9943-1.9961. In addition to these signals, a broad EPR signal grows in intensity below 80 K with g 4 = 2.1085-2.2438 which can be attributed to both paramagnetic Cp* 2 Cr + and H 2 Pc˙ - species having exchange interactions.

Computational modeling of heterogeneity and function of CD4+ T cells

PubMed Central

Carbo, Adria; Hontecillas, Raquel; Andrew, Tricity; Eden, Kristin; Mei, Yongguo; Hoops, Stefan; Bassaganya-Riera, Josep

2014-01-01

The immune system is composed of many different cell types and hundreds of intersecting molecular pathways and signals. This large biological complexity requires coordination between distinct pro-inflammatory and regulatory cell subsets to respond to infection while maintaining tissue homeostasis. CD4+ T cells play a central role in orchestrating immune responses and in maintaining a balance between pro- and anti- inflammatory responses. This tight balance between regulatory and effector reactions depends on the ability of CD4+ T cells to modulate distinct pathways within large molecular networks, since dysregulated CD4+ T cell responses may result in chronic inflammatory and autoimmune diseases. The CD4+ T cell differentiation process comprises an intricate interplay between cytokines, their receptors, adaptor molecules, signaling cascades and transcription factors that help delineate cell fate and function. Computational modeling can help to describe, simulate, analyze, and predict some of the behaviors in this complicated differentiation network. This review provides a comprehensive overview of existing computational immunology methods as well as novel strategies used to model immune responses with a particular focus on CD4+ T cell differentiation. PMID:25364738

Experimental implementation of fiber optic bundle array wide FOV free space optical communications receiver.

PubMed

Brown, Andrea M; Hahn, Daniel V; Brown, David M; Rolander, Nathan W; Bair, Chun-Huei; Sluz, Joseph E

2012-06-20

A gimbal-free wide field-of-regard (FOR) optical receiver has been built in a laboratory setting for proof-of-concept testing. Multiple datasets are presented that examine the overall FOR of the system and the receiver's ability to track and collect a signal from a moving source. The design is not intended to compete with traditional free space optical communication systems, but rather offer an alternative design that minimizes the number and complexity of mechanical components required at the surface of a small mobile platform. The receiver is composed of a micro-lens array and hexagonal bundles of large core optical fibers that route the optical signal to remote detectors and electronics. Each fiber in the bundle collects power from a distinct solid angle of space and a piezo-electric transducer is used to translate the micro-lens array and optimize coupling into a given fiber core in the bundle. The micro-lens to fiber bundle design is scalable, modular, and can be replicated in an array to increase aperture size.

Physiological controls of large‐scale patterning in planarian regeneration: a molecular and computational perspective on growth and form

PubMed Central

Durant, Fallon; Lobo, Daniel; Hammelman, Jennifer

2016-01-01

Abstract Planaria are complex metazoans that repair damage to their bodies and cease remodeling when a correct anatomy has been achieved. This model system offers a unique opportunity to understand how large‐scale anatomical homeostasis emerges from the activities of individual cells. Much progress has been made on the molecular genetics of stem cell activity in planaria. However, recent data also indicate that the global pattern is regulated by physiological circuits composed of ionic and neurotransmitter signaling. Here, we overview the multi‐scale problem of understanding pattern regulation in planaria, with specific focus on bioelectric signaling via ion channels and gap junctions (electrical synapses), and computational efforts to extract explanatory models from functional and molecular data on regeneration. We present a perspective that interprets results in this fascinating field using concepts from dynamical systems theory and computational neuroscience. Serving as a tractable nexus between genetic, physiological, and computational approaches to pattern regulation, planarian pattern homeostasis harbors many deep insights for regenerative medicine, evolutionary biology, and engineering. PMID:27499881

Analysis of the heterochromatin of Cebus (Primates, Platyrrhini) by micro-FISH and banding pattern comparisons.

PubMed

Nieves, Mariela; De Oliveira, Edivaldo H C; Amaral, Paulo J S; Nagamachi, Cleusa Y; Pieczarka, Julio C; Mühlmann, María C; Mudry, Marta D

2011-04-01

The karyotype of the neotropical primate genus Cebus (Platyrrhini: Cebidae), considered the most ancestral one, shows the greatest amount of heterochromatin described among Platyrrhini genera. Banding techniques and restriction enzyme digestion have previously revealed great variability of quantity and composition of heterochromatin in this genus. In this context, we use fluorescence in situ hybridization (FISH) to analyse this genomic region and discuss its possible role in the diversification of Cebus.We used a heterochromatin probe for chromosome 11 of Cebus libidinosus (11qHe+ CLI probe), obtained by chromosome microdissection. Twenty-six specimens belonging to the families Atelidae, Cebidae, Callitrichidae and Pithecidae (Platyrrhini) were studied. Fourteen out of 26 specimens were Cebus (Cebidae) individuals of C. libidinosus, C. xanthosternos, C. apella, C. nigritus, C. albifrons, C. kaapori and C. olivaceus. In Cebus specimens, we found 6 to 22 positive signals located in interstitial and telomeric positions along the different species. No hybridization signal was observed among the remaining Ceboidea species, thus reinforcing the idea of a Cebus-specific heterochromatin composed of a complex system of repetitive sequences.

Experimental study of boron-coated straws with a neutron source

NASA Astrophysics Data System (ADS)

Xie, Zhaoyang; Zhou, Jianrong; Song, Yushou; Lacy, Jeffrey L.; Sun, Liang; Sun, Zhijia; Hu, Bitao; Chen, Yuanbo

2018-04-01

Multiple types of high quality neutron detectors are proposed for the first phase of the China Spallation Neutron Source (CSNS), which will be commissioned in 2018. Considering the shortage of 3He supply, a detector module composed of 49 boron-coated straws (BCS) was developed by Proportional Technologies Inc. (PTI). Each straw has a length of 1000 mm and a diameter of 7.5 mm. Seven straws are tightly packed in a tube, and seven tubes are organized in a row to form a detector module. The charge division method is used for longitudinal positioning. A specific readout system was utilized to output the signal and simultaneously encode each straw. The performance of this detector module was studied using a moderated 252Cf source at the Institute of High Energy Physics (IHEP). The signal amplitude spectrum indicates its n-gamma discrimination capability. Despite the complex readout method, a longitudinal resolution of FWHM=6.1 ± 0.5 mm was obtained. The three-dimensional positioning ability qualifies this BCS detector module as a promising detector for small angle neutron scattering.

Sensory perception in the fungus Phycomyces blakesleeanus: a model organism for space research?

NASA Astrophysics Data System (ADS)

Corrochano, Luis M.

2016-07-01

Fungi use signals from the environment to regulate growth, development, and metabolism. The growth of the fruiting bodies, sporangiophores, of Phycomyces blakesleeanus is governed by several environmental signals, including light, gravity, touch, wind, and the presence of nearby objects. These signals allow sporangiophore growth towards open air for efficient spore dispersal. The sporangiophores of Phycomyces are giant isolated cells that can reach several cm in length. The large size of the sporangiophores facilitates genetic screens for tropic mutants, and the sexual cycle allows the genetic analysis of tropic mutations. The availability of the Phycomyces genome sequence and a collection of SNPs allow gene identification by genome mapping and gene sequencing. In addition, the size of the sporangiophore facilitates physiological analysis of tropic growth using computerized tracking devices. These experimental approaches will help to understand the mechanisms of sensory perception and how cell growth is regulated by environmental signals. The perception of light by Phycomyces has been investigated in most detail. Most fungi use proteins similar to WC-1 and WC-2 from Neurospora crassa for sensing blue light. In N. crassa and other fungi these two proteins form a photoreceptor and transcription factor complex that binds to the promoters of light-regulated genes to activate transcription. Phycomyces have multiple wc genes and two of them encode a photoreceptor complex composed of MadA and MadB that is required for all responses to light. The tropic response to gravity is much slower than to light, and require the presence of floating lipid globules and protein crystals that may be part of the gravity sensory system. Light and gravity interact to modify the direction of growth of the sporangiophore but the mechanisms that allow the coordination of a single response to different environmental signals remain to be defined. The giant sporangiophore of Phycomyces is an experimental system that should take advantage of the unique experimental conditions in space to understand the perception of gravity and other signals in a single eukaryotic cell.

Bidirectional Signaling of Mammary Epithelium and Stroma: Implications for Breast Cancer—Preventive Actions of Dietary Factors

USDA-ARS?s Scientific Manuscript database

The mammary gland is composed of two major cellular compartments: a highly dynamic epithelium that undergoes cycles of proliferation, differentiation, and apoptosis in response to local and endocrine signals and the underlying stroma comprised of fibroblasts, endothelial cells, and adipocytes that c...

Co-clustering of Fcgamma and B cell receptors induces dephosphorylation of the Grb2-associated binder 1 docking protein.

PubMed

Koncz, G; Tóth, G K; Bökönyi, G; Kéri, G; Pecht, I; Medgyesi, D; Gergely, J; Sármay, G

2001-07-01

The immunoreceptor tyrosine-based inhibitory motif (ITIM) of human type IIb Fcgamma receptor (FcgammaRIIb) is phosphorylated on its tyrosine upon co-clustering with the B cell receptor (BCR). The phosphorylated ITIM (p-ITIM) binds to the SH2 domains of polyphosphoinositol 5-phosphatase (SHIP) and the tyrosine phosphatase, SHP-2. We investigated the involvement of the molecular complex composed of the phosphorylated SHIP and FcgammaRIIb in the activation of SHP-2. As a model compound, we synthesized a bisphosphopeptide, combining the sequences of p-ITIM and the N-terminal tyrosine phosphorylated motif of SHIP with a flexible spacer. This compound bound to the recombinant SH2 domains of SHP-2 with high affinity and activated the phosphatase in an in vitro assay. These data suggest that the phosphorylated FcgammaRII-SHIP complexes formed in the intact cells may also activate SHP-2. Grb2-associated binder 1 (Gab1) is a multisite docking protein, which becomes tyrosine-phosphorylated in response to various types of signaling, including BCR. In turn it binds to the SH2 domains of SHP-2, SHIP and the p85 subunit of phosphatidyl inositol 3-kinase (PtdIns3-K) and may regulate their activity. Gab1 is a potential substrate of SHP-2, thus its binding to FcgammaRIIb may modify the Gab1-bound signaling complex. We show here that Gab1 is part of the multiprotein complex assembled by FcgammaRIIb upon its co-clustering with BCR. Gab1 may recruit SH2 domain-containing molecules to the phosphorylated FcgammaRIIb. SHP-2, activated upon the binding to FcgammaRIIb-SHIP complex, partially dephosphorylates Gab1, resulting in the release of PtdIns3-K and ultimately in the inhibition of downstream activation pathways in BCR/FcgammaRIIb co-aggregated cells.

mTOR in Down syndrome: Role in Aß and tau neuropathology and transition to Alzheimer disease-like dementia.

PubMed

Di Domenico, Fabio; Tramutola, Antonella; Foppoli, Cesira; Head, Elizabeth; Perluigi, Marzia; Butterfield, D Allan

2018-01-01

The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase involved in the regulation of protein synthesis and degradation, longevity and cytoskeletal formation. The mTOR pathway represents a key growth and survival pathway involved in several diseases such as cancer, obesity, cardiovascular disease and neurodegenerative diseases. Numerous studies linked the alterations of mTOR pathway to age-dependent cognitive decline, pathogenesis of Alzheimer disease (AD) and AD-like dementia in Down syndrome (DS). DS is the most frequent chromosomal abnormality that causes intellectual disability. The neuropathology of AD in DS is complex and involves impaired mitochondrial function, defects in neurogenesis, increased oxidative stress, altered proteostasis and autophagy networks as a result of triplication of chromosome 21(chr 21). The chr21 gene products are considered a principal neuropathogenic moiety in DS. Several genes involved respectively in the formation of senile plaques and neurofibrillary tangles (NFT), two main pathological hallmarks of AD, are mapped on chr21. Further, in subjects with DS the activation of mTOR signaling contributes to Aβ generation and the formation of NFT. This review discusses recent research highlighting the complex role of mTOR associated with the presence of two hallmarks of AD pathology, senile plaques (composed mostly of fibrillar Aß peptides), and NFT (composed mostly of hyperphosphorylated tau protein). Oxidative stress, associated with chr21-related Aβ and mitochondrial alterations, may significantly contribute to this linkage of mTOR to AD-like neuropathology in DS. Copyright © 2017 Elsevier Inc. All rights reserved.

Elimination of autofluorescence background from fluorescence tissue images by use of time-gated detection and the AzaDiOxaTriAngulenium (ADOTA) fluorophore.

PubMed

Rich, Ryan M; Stankowska, Dorota L; Maliwal, Badri P; Sørensen, Thomas Just; Laursen, Bo W; Krishnamoorthy, Raghu R; Gryczynski, Zygmunt; Borejdo, Julian; Gryczynski, Ignacy; Fudala, Rafal

2013-02-01

Sample autofluorescence (fluorescence of inherent components of tissue and fixative-induced fluorescence) is a significant problem in direct imaging of molecular processes in biological samples. A large variety of naturally occurring fluorescent components in tissue results in broad emission that overlaps the emission of typical fluorescent dyes used for tissue labeling. In addition, autofluorescence is characterized by complex fluorescence intensity decay composed of multiple components whose lifetimes range from sub-nanoseconds to a few nanoseconds. For these reasons, the real fluorescence signal of the probe is difficult to separate from the unwanted autofluorescence. Here we present a method for reducing the autofluorescence problem by utilizing an azadioxatriangulenium (ADOTA) dye with a fluorescence lifetime of approximately 15 ns, much longer than those of most of the components of autofluorescence. A probe with such a long lifetime enables us to use time-gated intensity imaging to separate the signal of the targeting dye from the autofluorescence. We have shown experimentally that by discarding photons detected within the first 20 ns of the excitation pulse, the signal-to-background ratio is improved fivefold. This time-gating eliminates over 96 % of autofluorescence. Analysis using a variable time-gate may enable quantitative determination of the bound probe without the contributions from the background.

Rapid evolution of cuticular hydrocarbons in a species radiation of acoustically diverse Hawaiian crickets (Gryllidae: trigonidiinae: Laupala).

PubMed

Mullen, Sean P; Mendelson, Tamra C; Schal, Coby; Shaw, Kerry L

2007-01-01

Understanding the origin and maintenance of barriers to gene exchange is a central goal of speciation research. Hawaiian swordtail crickets (genus Laupala) represent one of the most rapidly speciating animal groups yet identified. Extensive acoustic diversity, strong premating isolation, and female preference for conspecific acoustic signals in laboratory phonotaxis trials have strongly supported divergence in mate recognition as the driving force behind the explosive speciation seen in this system. However, recent work has shown that female preference for conspecific male calling song does not extend to mate choice at close range among these crickets, leading to the hypothesis that additional sexual signals are involved in mate recognition and premating isolation. Here we examine patterns of variation in cuticular lipids among several species of Laupala from Maui and the Big Island of Hawaii. Results demonstrate (1) a rapid and dramatic evolution of cuticular lipid composition among species in this genus, (2) significant differences among males and females in cuticular lipid composition, and (3) a significant reduction in the complexity of cuticular lipid profiles in species from the Big Island of Hawaii as compared to two outgroup species from Maui. These results suggest that behavioral barriers to gene exchange in Laupala may be composed of multiple mate recognition signals, a pattern common in other cricket species.

Location of Biomarkers and Reagents within Agarose Beads of a Programmable Bio-nano-chip

PubMed Central

Jokerst, Jesse V.; Chou, Jie; Camp, James P.; Wong, Jorge; Lennart, Alexis; Pollard, Amanda A.; Floriano, Pierre N.; Christodoulides, Nicolaos; Simmons, Glennon W.; Zhou, Yanjie; Ali, Mehnaaz F.

2012-01-01

The slow development of cost-effective medical microdevices with strong analytical performance characteristics is due to a lack of selective and efficient analyte capture and signaling. The recently developed programmable bio-nano-chip (PBNC) is a flexible detection device with analytical behavior rivaling established macroscopic methods. The PBNC system employs ≈300 μm-diameter bead sensors composed of agarose “nanonets” that populate a microelectromechanical support structure with integrated microfluidic elements. The beads are an efficient and selective protein-capture medium suitable for the analysis of complex fluid samples. Microscopy and computational studies probe the 3D interior of the beads. The relative contributions that the capture and detection of moieties, analyte size, and bead porosity make to signal distribution and intensity are reported. Agarose pore sizes ranging from 45 to 620 nm are examined and those near 140 nm provide optimal transport characteristics for rapid (<15 min) tests. The system exhibits efficient (99.5%) detection of bead-bound analyte along with low (≈2%) nonspecific immobilization of the detection probe for carcinoembryonic antigen assay. Furthermore, the role analyte dimensions play in signal distribution is explored, and enhanced methods for assay building that consider the unique features of biomarker size are offered. PMID:21290601

IgG Fab Fragments Forming Bivalent Complexes by a Conformational Mechanism That Is Reversible by Osmolytes*

PubMed Central

Nelson, Alfreda D.; Hoffmann, Michele M.; Parks, Christopher A.; Dasari, Surendra; Schrum, Adam G.; Gil, Diana

2012-01-01

Generated by proteolytic cleavage of immunoglobulin, Fab fragments possess great promise as blocking reagents, able to bind receptors or other targets without inducing cross-linking. However, aggregation of Fab preparations is a common occurrence, which generates intrinsic stimulatory capacity and thwarts signal blockade strategies. Using a panel of biochemical approaches, including size exclusion chromatography, SDS-PAGE, mass spectrometry, and cell stimulation followed by flow cytometry, we have measured the oligomerization and acquisition of stimulatory capacity that occurs in four monoclonal IgG Fabs specific for TCR/CD3. Unexpectedly, we observed that all Fabs spontaneously formed complexes that were precisely bivalent, and these bivalent complexes possessed most of the stimulatory activity of each Fab preparation. Fabs composing bivalent complexes were more susceptible to proteolysis than monovalent Fabs, indicating a difference in conformation between the Fabs involved in these two different states of valency. Because osmolytes represent a class of compounds that stabilize protein folding and conformation, we sought to determine the extent to which the amino acid osmolyte l-proline might impact bivalent Fab complexation. We found that l-proline (i) inhibited the adoption of the conformation associated with bivalent complexation, (ii) preserved Fab monovalency, (iii) reversed the conformation of preformed bivalent Fabs to that of monovalent Fabs, and (iv) separated a significant percentage of preformed bivalent complexes into monovalent species. Thus, Fab fragments can adopt a conformation that is compatible with folding or packing of a bivalent complex in a process that can be inhibited by osmolytes. PMID:23109335

Distribution of metabotropic receptors of serotonin, dopamine, GABA, glutamate, and short neuropeptide F in the central complex of Drosophila.

PubMed

Kahsai, L; Carlsson, M A; Winther, A M E; Nässel, D R

2012-04-19

The central complex is a prominent set of midline neuropils in the insect brain, known to be a higher locomotor control center that integrates visual inputs and modulates motor outputs. It is composed of four major neuropil structures, the ellipsoid body (EB), fan-shaped body (FB), noduli (NO), and protocerebral bridge (PB). In Drosophila different types of central complex neurons have been shown to express multiple neuropeptides and neurotransmitters; however, the distribution of corresponding receptors is not known. Here, we have mapped metabotropic, G-protein-coupled receptors (GPCRs) of several neurotransmitters to neurons of the central complex. By combining immunocytochemistry with GAL4 driven green fluorescent protein, we examined the distribution patterns of six different GPCRs: two serotonin receptor subtypes (5-HT(1B) and 5-HT(7)), a dopamine receptor (DopR), the metabotropic GABA(B) receptor (GABA(B)R), the metabotropic glutamate receptor (DmGluR(A)) and a short neuropeptide F receptor (sNPFR1). Five of the six GPCRs were mapped to different neurons in the EB (sNPFR1 was not seen). Different layers of the FB express DopR, GABA(B)R, DmGluR(A,) and sNPFR1, whereas only GABA(B)R and DmGluR(A) were localized to the PB. Finally, strong expression of DopR and DmGluR(A) was detected in the NO. In most cases the distribution patterns of the GPCRs matched the expression of markers for their respective ligands. In some nonmatching regions it is likely that other types of dopamine and serotonin receptors or ionotropic GABA and glutamate receptors are expressed. Our data suggest that chemical signaling and signal modulation are diverse and highly complex in the different compartments and circuits of the Drosophila central complex. The information provided here, on receptor distribution, will be very useful for future analysis of functional circuits in the central complex, based on targeted interference with receptor expression. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Mechanistic and signaling analysis of Muc4-ErbB2 signaling module: new insights into the mechanism of ligand-independent ErbB2 activity.

PubMed

Kozloski, Goldi A; Carraway, Coralie A Carothers; Carraway, Kermit L

2010-09-01

The membrane mucin Muc4 is aberrantly expressed in numerous epithelial carcinomas and is currently used as a cancer diagnostic and prognostic tool. Muc4 can also potentiate signal transduction by modulating differential ErbB2 phosphorylation in the absence and in the presence of the ErbB3 soluble ligand heregulin (HRG-beta1). These features of Muc4 suggest that Muc4 is not merely a cancer marker, but an oncogenic factor with a unique-binding/activation relationship with the receptor ErbB2. In the present study, we examined the signaling mechanisms that are associated with the Muc4-ErbB2 module by analyzing ErbB2 differential signaling in response to Muc4 expression. Our study was carried out in the A375 human melanoma and BT-474 breast cancer cell lines as our model systems. Quantitative and comparative signaling modulations were evaluated by immunoblot using phospho-specific antibodies, and densitometry analysis. Signaling complex components were identified by chemical cross-linking, fractionation by gel filtration, immunoprecipitation, and immunoblotting. Activated downstream signaling pathways were analyzed by an antibody microarray screen and immunoblot analyses. Our results indicate that Muc4 modulates ErbB2 signaling potential significantly by stabilizing and directly interacting with the ErbB2-ErbB3 heterodimer. Further analyses indicate that Muc4 promotes ErbB2 autocatalysis, but it has no effect on ErbB3 phosphorylation, although the chemical cross-linking data indicated that the signaling module is composed of Muc4, ErbB2, and ErbB3. Our microarray analysis indicates that Muc4 expression promotes cell migration by increasing the phosphorylation of the focal adhesion kinase and also through an increase in the levels of beta-catenin. (c) 2010 Wiley-Liss, Inc.

A novel method to accurately locate and count large numbers of steps by photobleaching.

PubMed

Tsekouras, Konstantinos; Custer, Thomas C; Jashnsaz, Hossein; Walter, Nils G; Pressé, Steve

2016-11-07

Photobleaching event counting is a single-molecule fluorescence technique that is increasingly being used to determine the stoichiometry of protein and RNA complexes composed of many subunits in vivo as well as in vitro. By tagging protein or RNA subunits with fluorophores, activating them, and subsequently observing as the fluorophores photobleach, one obtains information on the number of subunits in a complex. The noise properties in a photobleaching time trace depend on the number of active fluorescent subunits. Thus, as fluorophores stochastically photobleach, noise properties of the time trace change stochastically, and these varying noise properties have created a challenge in identifying photobleaching steps in a time trace. Although photobleaching steps are often detected by eye, this method only works for high individual fluorophore emission signal-to-noise ratios and small numbers of fluorophores. With filtering methods or currently available algorithms, it is possible to reliably identify photobleaching steps for up to 20-30 fluorophores and signal-to-noise ratios down to ∼1. Here we present a new Bayesian method of counting steps in photobleaching time traces that takes into account stochastic noise variation in addition to complications such as overlapping photobleaching events that may arise from fluorophore interactions, as well as on-off blinking. Our method is capable of detecting ≥50 photobleaching steps even for signal-to-noise ratios as low as 0.1, can find up to ≥500 steps for more favorable noise profiles, and is computationally inexpensive. © 2016 Tsekouras et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Hippocampus and serum metabolomic studies to explore the regulation of Chaihu-Shu-Gan-San on metabolic network disturbances of rats exposed to chronic variable stress.

PubMed

Su, Zhi-heng; Jia, Hong-mei; Zhang, Hong-wu; Feng, Yu-Fei; An, Lei; Zou, Zhong-mei

2014-03-04

Chaihu-Shu-Gan-San (CSGS), a traditional Chinese medicine formula, has been effectively used for the treatment of depression. However, studies of its anti-depressive mechanism are challenging, due to the complex pathophysiology of depression, and complexity of CSGS with multiple constituents acting on different receptors. In the present work, metabolomic studies of biochemical changes in the hippocampus and serum of chronic variable stress (CVS)-induced depression rats after treatment with CSGS were performed using ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Partial least squares-discriminate analysis indicated that the metabolic perturbation induced by CVS was reduced by treatment with CSGS. A total of twenty-six metabolites (16 from the hippocampus and 10 from serum) were considered as potential biomarkers involved in the development of depression. Among them, 11 were first reported to have potential relevance in the pathogenesis of depression, and 25 may correlate to the regulation of CSGS treatment on depression. The results combined with a previous study indicated that CSGS mediated synergistically abnormalities of the metabolic network, composed of energy metabolism, synthesis of neurotransmitters, tryptophan, phospholipids, fatty acid and bile acid metabolism, bone loss and liver detoxification, which may be helpful for understanding its mechanism of action. Furthermore, the extracellular signal-regulated kinase (ERK) signal pathway, involved in the neuronal protective mechanism of depression related to energy metabolism, was investigated by western blot analysis. The results showed that CSGS reversed disruptions of BDNF, ERK1/2 and pERK1/2 in CVS rats, which provides the first evidence that the ERK signal system may be one of the targets related to the antidepressant action of CSGS.

Detection of Mycobacterium tuberculosis based on H37R(v) binding peptides using surface functionalized magnetic microspheres coupled with quantum dots – a nano detection method for Mycobacterium tuberculosis.

PubMed

Yang, Hua; Qin, Lianhua; Wang, Yilong; Zhang, Bingbo; Liu, Zhonghua; Ma, Hui; Lu, Junmei; Huang, Xiaochen; Shi, Donglu; Hu, Zhongyi

2015-01-01

Despite suffering from the major disadvantage of low sensitivity, microscopy of direct smear with the Ziehl-Neelsen stain is still broadly used for detection of acid-fast bacilli and diagnosis of tuberculosis. Here, we present a unique detection method of Mycobacterium tuberculosis (MTB) using surface functionalized magnetic microspheres (MMSs) coupled with quantum dots (QDs), conjugated with various antibodies and phage display-derived peptides. The principle is based upon the conformation of the sandwich complex composed of bacterial cells, MMSs, and QDs. The complex system is tagged with QDs for providing the fluorescent signal as part of the detection while magnetic separation is achieved by MMSs. The peptide ligand H8 derived from the phage display library Ph.D.-7 is developed for MTB cells. Using the combinations of MMS-polyclonal antibody+QD-H8 and MMS-H8+QD-H8, a strong signal of 10(3) colony forming units (CFU)/mL H37R(v) was obtained with improved specificity. MS-H8+QD-H8 combination was further optimized by adjusting the concentrations of MMSs, QDs, and incubation time for the maximum detection signal. The limit of detection for MTB was found to reach 10(3) CFU/mL even for the sputum matrices. Positive sputum samples could be distinguished from control. Thus, this novel method is shown to improve the detection limit and specificity of MTB from the sputum samples, and to reduce the testing time for accurate diagnosis of tuberculosis, which needs further confirmation of more clinical samples.

Mitochondrial flash as a novel biomarker of mitochondrial respiration in the heart.

PubMed

Gong, Guohua; Liu, Xiaoyun; Zhang, Huiliang; Sheu, Shey-Shing; Wang, Wang

2015-10-01

Mitochondrial respiration through electron transport chain (ETC) activity generates ATP and reactive oxygen species in eukaryotic cells. The modulation of mitochondrial respiration in vivo or under physiological conditions remains elusive largely due to the lack of appropriate approach to monitor ETC activity in a real-time manner. Here, we show that ETC-coupled mitochondrial flash is a novel biomarker for monitoring mitochondrial respiration under pathophysiological conditions in cultured adult cardiac myocyte and perfused beating heart. Through real-time confocal imaging, we follow the frequency of a transient bursting fluorescent signal, named mitochondrial flash, from individual mitochondria within intact cells expressing a mitochondrial matrix-targeted probe, mt-cpYFP (mitochondrial-circularly permuted yellow fluorescent protein). This mt-cpYFP recorded mitochondrial flash has been shown to be composed of a major superoxide signal with a minor alkalization signal within the mitochondrial matrix. Through manipulating physiological substrates for mitochondrial respiration, we find a close coupling between flash frequency and the ETC electron flow, as measured by oxygen consumption rate in cardiac myocyte. Stimulating electron flow under physiological conditions increases flash frequency. On the other hand, partially block or slowdown electron flow by inhibiting the F0F1 ATPase, which represents a pathological condition, transiently increases then decreases flash frequency. Limiting electron entrance at complex I by knocking out Ndufs4, an assembling subunit of complex I, suppresses mitochondrial flash activity. These results suggest that mitochondrial electron flow can be monitored by real-time imaging of mitochondrial flash. The mitochondrial flash frequency could be used as a novel biomarker for mitochondrial respiration under physiological and pathological conditions. Copyright © 2015 the American Physiological Society.

Detection of Mycobacterium tuberculosis based on H37Rv binding peptides using surface functionalized magnetic microspheres coupled with quantum dots – a nano detection method for Mycobacterium tuberculosis

PubMed Central

Yang, Hua; Qin, Lianhua; Wang, Yilong; Zhang, Bingbo; Liu, Zhonghua; Ma, Hui; Lu, Junmei; Huang, Xiaochen; Shi, Donglu; Hu, Zhongyi

2015-01-01

Despite suffering from the major disadvantage of low sensitivity, microscopy of direct smear with the Ziehl–Neelsen stain is still broadly used for detection of acid-fast bacilli and diagnosis of tuberculosis. Here, we present a unique detection method of Mycobacterium tuberculosis (MTB) using surface functionalized magnetic microspheres (MMSs) coupled with quantum dots (QDs), conjugated with various antibodies and phage display-derived peptides. The principle is based upon the conformation of the sandwich complex composed of bacterial cells, MMSs, and QDs. The complex system is tagged with QDs for providing the fluorescent signal as part of the detection while magnetic separation is achieved by MMSs. The peptide ligand H8 derived from the phage display library Ph.D.-7 is developed for MTB cells. Using the combinations of MMS-polyclonal antibody+QD-H8 and MMS-H8+QD-H8, a strong signal of 103 colony forming units (CFU)/mL H37Rv was obtained with improved specificity. MS-H8+QD-H8 combination was further optimized by adjusting the concentrations of MMSs, QDs, and incubation time for the maximum detection signal. The limit of detection for MTB was found to reach 103 CFU/mL even for the sputum matrices. Positive sputum samples could be distinguished from control. Thus, this novel method is shown to improve the detection limit and specificity of MTB from the sputum samples, and to reduce the testing time for accurate diagnosis of tuberculosis, which needs further confirmation of more clinical samples. PMID:25565805

Altered Protein Interactions of the Endogenous Interactome of PTPIP51 towards MAPK Signaling

PubMed Central

Brobeil, Alexander; Chehab, Rajaa; Dietel, Eric; Gattenlöhner, Stefan; Wimmer, Monika

2017-01-01

Protein–protein interactions play a pivotal role in normal cellular functions as well as in carcinogenesis. The protein–protein interactions form functional clusters during signal transduction. To elucidate the fine calibration of the protein–protein interactions of protein tyrosine phosphatase interacting protein 51 (PTPIP51) a small molecule drug, namely LDC-3, directly targeting PTPIP51 is now available. Therefore, LDC-3 allows for the studying of the regulation of the endogenous interactome by modulating PTPIP51 binding capacity. Small interfering ribonucleic acid (siRNA) experiments show that the modification in PTPIP51 binding capacity is induced by LDC-3. Application of LDC-3 annuls the known regulatory phosphorylation mechanisms for PTPIP51 and consequently, significantly alters the assembly of the PTPIP51 associated protein complexes. The treatment of human keratinocytes (HaCaT cells) with LDC-3 induces an altered protein–protein interaction profile of the endogenous interactome of PTPIP51. In addition, LDC-3 stabilizes PTPIP51 within a mitogen activated protein kinase (MAPK) complex composed of Raf-1 and the scaffold protein 14-3-3, independent of the phosphorylation status of PTPIP51. Of note, under LDC-3 treatment the regulatory function of the PTP1B on PTPIP51 fails to impact the PTPIP51 interaction characteristics, as reported for the HaCaT cell line. In summary, LDC-3 gives the unique opportunity to directly modulate PTPIP51 in malignant cells, thus targeting potential dysregulated signal transduction pathways such as the MAPK cascade. The provided data give critical insights in the therapeutic potential of PTPIP51 protein interactions and thus are basic for possible targeted therapy regimens. PMID:28754031

Characterization of real objects by an active electrolocation sensor

NASA Astrophysics Data System (ADS)

Metzen, Michael G.; Al Ghouz, Imène; Krueger, Sandra; Bousack, Herbert; von der Emde, Gerhard

2012-04-01

Weakly electric fish use a process called 'active electrolocation' to orientate in their environment and to localize objects based on their electrical properties. To do so, the fish discharge an electric organ which emits brief electrical current pulses (electric organ discharge, EOD) and in return sense the generated electric field which builds up surrounding the animal. Caused by the electrical properties of nearby objects, fish measure characteristic signal modulations with an array of electroreceptors in their skin. The fish are able to gain important information about the geometrical properties of an object as well as its complex impedance and its distance. Thus, active electrolocation is an interesting feature to be used in biomimetic approaches. We used this sensory principle to identify different insertions in the walls of Plexiglas tubes. The insertions tested were composed of aluminum, brass and graphite in sizes between 3 and 20 mm. A carrier signal was emitted and perceived with the poles of a commercial catheter for medical diagnostics. Measurements were performed with the poles separated by 6.3 to 55.3 mm. Depending on the length of the insertion in relation to the sender-receiver distance, we observed up to three peaks in the measured electric images. The first peak was affected by the material of the insertion, while the distance between the second and third peak strongly correlated with the length of the insertion. In a second experiment we tested whether various materials could be detected by using signals of different frequency compositions. Based on their electric images we were able to discriminate between objects having different resistive properties, but not between objects of complex impedances.

Immunohistochemical, cytogenetic, and molecular cytogenetic characterization of both components of a dedifferentiated liposarcoma: implications for histogenesis.

PubMed

Nishio, Jun; Iwasaki, Hiroshi; Nabeshima, Kazuki; Naito, Masatoshi

2015-01-01

Dedifferentiated liposarcoma (DDLS) is a malignant adipocytic tumor showing transition from an atypical lipomatous tumor (ALT)/well-differentiated liposarcoma (WDLS) to a non-lipogenic sarcoma of variable histological grades. We present the immunohistochemical, cytogenetic, and molecular cytogenetic findings of DDLS arising in the right chest wall of a 76-year-old man. Magnetic resonance imaging exhibited a large mass composed of two components with heterogeneous signal intensities, suggesting the coexistence of a fatty area and another soft tissue component. The grossly heterogeneous mass was histologically composed of an ALT/WDLS component transitioning abruptly into a dedifferentiated component. Immunohistochemistry was positive for murine double-minute 2 (MDM2), cyclin-dependent kinase 4 (CDK4), and p16 in both components, although a more strong and diffuse staining was found in the dedifferentiated area. The MIB-1 labeling index was extremely higher in the dedifferentiated area compared to the ALT/WDLS area. Cytogenetic analysis of the ALT/WDLS component revealed the following karyotype: 46,X,-Y,+r. Notably, cytogenetic analysis of the dedifferentiated component revealed a similar but more complex karyotype. Spectral karyotyping demonstrated that the ring chromosome was entirely composed of material from chromosome 12. Interphase fluorescence in situ hybridization analysis revealed amplification of MDM2 and CDK4 in both components. These findings suggest that multiple abnormal clones derived from a single precursor cell would be present in DDLS, with one or more containing supernumerary rings or giant marker chromosomes. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Composing only by thought: Novel application of the P300 brain-computer interface.

PubMed

Pinegger, Andreas; Hiebel, Hannah; Wriessnegger, Selina C; Müller-Putz, Gernot R

2017-01-01

The P300 event-related potential is a well-known pattern in the electroencephalogram (EEG). This kind of brain signal is used for many different brain-computer interface (BCI) applications, e.g., spellers, environmental controllers, web browsers, or for painting. In recent times, BCI systems are mature enough to leave the laboratories to be used by the end-users, namely severely disabled people. Therefore, new challenges arise and the systems should be implemented and evaluated according to user-centered design (USD) guidelines. We developed and implemented a new system that utilizes the P300 pattern to compose music. Our Brain Composing system consists of three parts: the EEG acquisition device, the P300-based BCI, and the music composing software. Seventeen musical participants and one professional composer performed a copy-spelling, a copy-composing, and a free-composing task with the system. According to the USD guidelines, we investigated the efficiency, the effectiveness and subjective criteria in terms of satisfaction, enjoyment, frustration, and attractiveness. The musical participants group achieved high average accuracies: 88.24% (copy-spelling), 88.58% (copy-composing), and 76.51% (free-composing). The professional composer achieved also high accuracies: 100% (copy-spelling), 93.62% (copy-composing), and 98.20% (free-composing). General results regarding the subjective criteria evaluation were that the participants enjoyed the usage of the Brain Composing system and were highly satisfied with the system. Showing very positive results with healthy people in this study, this was the first step towards a music composing system for severely disabled people.

Composing only by thought: Novel application of the P300 brain-computer interface

PubMed Central

Hiebel, Hannah; Wriessnegger, Selina C.; Müller-Putz, Gernot R.

2017-01-01

The P300 event-related potential is a well-known pattern in the electroencephalogram (EEG). This kind of brain signal is used for many different brain-computer interface (BCI) applications, e.g., spellers, environmental controllers, web browsers, or for painting. In recent times, BCI systems are mature enough to leave the laboratories to be used by the end-users, namely severely disabled people. Therefore, new challenges arise and the systems should be implemented and evaluated according to user-centered design (USD) guidelines. We developed and implemented a new system that utilizes the P300 pattern to compose music. Our Brain Composing system consists of three parts: the EEG acquisition device, the P300-based BCI, and the music composing software. Seventeen musical participants and one professional composer performed a copy-spelling, a copy-composing, and a free-composing task with the system. According to the USD guidelines, we investigated the efficiency, the effectiveness and subjective criteria in terms of satisfaction, enjoyment, frustration, and attractiveness. The musical participants group achieved high average accuracies: 88.24% (copy-spelling), 88.58% (copy-composing), and 76.51% (free-composing). The professional composer achieved also high accuracies: 100% (copy-spelling), 93.62% (copy-composing), and 98.20% (free-composing). General results regarding the subjective criteria evaluation were that the participants enjoyed the usage of the Brain Composing system and were highly satisfied with the system. Showing very positive results with healthy people in this study, this was the first step towards a music composing system for severely disabled people. PMID:28877175

Man-Machine Interface System for Neuromuscular Training and Evaluation Based on EMG and MMG Signals

PubMed Central

de la Rosa, Ramon; Alonso, Alonso; Carrera, Albano; Durán, Ramon; Fernández, Patricia

2010-01-01

This paper presents the UVa-NTS (University of Valladolid Neuromuscular Training System), a multifunction and portable Neuromuscular Training System. The UVa-NTS is designed to analyze the voluntary control of severe neuromotor handicapped patients, their interactive response, and their adaptation to neuromuscular interface systems, such as neural prostheses or domotic applications. Thus, it is an excellent tool to evaluate the residual muscle capabilities in the handicapped. The UVa-NTS is composed of a custom signal conditioning front-end and a computer. The front-end electronics is described thoroughly as well as the overall features of the custom software implementation. The software system is composed of a set of graphical training tools and a processing core. The UVa-NTS works with two classes of neuromuscular signals: the classic myoelectric signals (MES) and, as a novelty, the myomechanic signals (MMS). In order to evaluate the performance of the processing core, a complete analysis has been done to classify its efficiency and to check that it fulfils with the real-time constraints. Tests were performed both with healthy and selected impaired subjects. The adaptation was achieved rapidly, applying a predefined protocol for the UVa-NTS set of training tools. Fine voluntary control was demonstrated to be reached with the myoelectric signals. And the UVa-NTS demonstrated to provide a satisfactory voluntary control when applying the myomechanic signals. PMID:22163515

Man-machine interface system for neuromuscular training and evaluation based on EMG and MMG signals.

PubMed

de la Rosa, Ramon; Alonso, Alonso; Carrera, Albano; Durán, Ramon; Fernández, Patricia

2010-01-01

This paper presents the UVa-NTS (University of Valladolid Neuromuscular Training System), a multifunction and portable Neuromuscular Training System. The UVa-NTS is designed to analyze the voluntary control of severe neuromotor handicapped patients, their interactive response, and their adaptation to neuromuscular interface systems, such as neural prostheses or domotic applications. Thus, it is an excellent tool to evaluate the residual muscle capabilities in the handicapped. The UVa-NTS is composed of a custom signal conditioning front-end and a computer. The front-end electronics is described thoroughly as well as the overall features of the custom software implementation. The software system is composed of a set of graphical training tools and a processing core. The UVa-NTS works with two classes of neuromuscular signals: the classic myoelectric signals (MES) and, as a novelty, the myomechanic signals (MMS). In order to evaluate the performance of the processing core, a complete analysis has been done to classify its efficiency and to check that it fulfils with the real-time constraints. Tests were performed both with healthy and selected impaired subjects. The adaptation was achieved rapidly, applying a predefined protocol for the UVa-NTS set of training tools. Fine voluntary control was demonstrated to be reached with the myoelectric signals. And the UVa-NTS demonstrated to provide a satisfactory voluntary control when applying the myomechanic signals.

Disorders of lysosomal acidification - the emerging role of v-ATPase in aging and neurodegenerative disease

PubMed Central

Colacurcio, Daniel J.; Nixon, Ralph A.

2016-01-01

Autophagy and endocytosis deliver unneeded cellular materials to lysosomes for degradation. Beyond processing cellular waste, lysosomes release metabolites and ions that serve signaling and nutrient sensing roles, linking the functions of the lysosome to various pathways for intracellular metabolism and nutrient homeostasis. Each of these lysosomal behaviors is influenced by the intraluminal pH of the lysosome, which is maintained in the low acidic range by a proton pump, the vacuolar ATPase (v-ATPase). New reports implicate altered v-ATPase activity and lysosomal pH dysregulation in cellular aging, longevity, and adult-onset neurodegenerative diseases, including forms of Parkinson Disease and Alzheimer Disease. Genetic defects of subunits composing the v-ATPase or v-ATPase-related proteins occur in an increasingly recognized group of familial neurodegenerative diseases. Here, we review the expanding roles of the v-ATPase complex as a platform regulating lysosomal proteolysis and cellular homeostasis. We discuss the unique vulnerability of neurons to persistent low level lysosomal dysfunction and review recent clinical and experimental studies that link dysfunction of the v-ATPase complex to neurodegenerative diseases across the age spectrum. PMID:27197071

Low-Cost Synthesis of Smart Biocompatible Graphene Oxide Reduced Species by Means of GFP.

PubMed

Masullo, Tiziana; Armata, Nerina; Pendolino, Flavio; Colombo, Paolo; Lo Celso, Fabrizio; Mazzola, Salvatore; Cuttitta, Angela

2016-02-01

The aim of this work is focused on the engineering of biocompatible complex systems composed of an inorganic and bio part. Graphene oxide (GO) and/or graphite oxide (GtO) were taken into account as potential substrates to the linkage of the protein such as Anemonia sulcata recombinant green fluorescent protein (rAsGFP). The complex system is obtained through a reduction process between GO/GtO and rAsGFP archiving an environmentally friendly biosynthesis. Spectroscopic measurements support the formation of reduced species. In particular, photoluminescence shows a change in the activity of the protein when a bond is formed, highlighted by a loss of the maximum emission signal of rAsGFP and a redshift of the maximum absorption peak of the GO/GtO species. Moreover, the hemolysis assay reveals a lower value in the presence of less oxidized graphene species providing evidence for a biocompatible material. This singular aspect can be approached as a promising method for circulating pharmaceutical preparations via intravenous administration in the field of drug delivery.

Biofabrication strategies for 3D in vitro models and regenerative medicine

NASA Astrophysics Data System (ADS)

Moroni, Lorenzo; Burdick, Jason A.; Highley, Christopher; Lee, Sang Jin; Morimoto, Yuya; Takeuchi, Shoji; Yoo, James J.

2018-05-01

Organs are complex systems composed of different cells, proteins and signalling molecules that are arranged in a highly ordered structure to orchestrate a myriad of functions in our body. Biofabrication strategies can be applied to engineer 3D tissue models in vitro by mimicking the structure and function of native tissue through the precise deposition and assembly of materials and cells. This approach allows the spatiotemporal control over cell-cell and cell-extracellular matrix communication and thus the recreation of tissue-like structures. In this Review, we examine biofabrication strategies for the construction of functional tissue replacements and organ models, focusing on the development of biomaterials, such as supramolecular and photosensitive materials, that can be processed using biofabrication techniques. We highlight bioprinted and bioassembled tissue models and survey biofabrication techniques for their potential to recreate complex tissue properties, such as shape, vasculature and specific functionalities. Finally, we discuss challenges, such as scalability and the foreign body response, and opportunities in the field and provide an outlook to the future of biofabrication in regenerative medicine.

Critical issues for engineering cord blood stem cells to produce insulin.

PubMed

Denner, Larry; Urban, Randall J

2008-09-01

The objectives of using cord blood stem cells for treating type 1 diabetes are simple in principle yet complex in biological and molecular mechanisms. These are defined by the complexity of the insulin-producing unit of the pancreas, the islet. Islets are composed of various cell types that arise from diverse lineages and communicate by hormones, growth factors and small-molecule mediators. These processes are regulated by integration of signal transduction pathways. While advances have been made to engineer umbilical cord blood stem cells to produce insulin, these studies only illuminate the potential of such cells to fulfil a necessary, but not sufficient, requirement for transplantation. The challenges ahead demand detailed understanding of molecular mechanisms to move from an opportunistic, phenotypic approach to transplantation and amelioration of blood glucose, to an orderly and logical approach to a biologically and medically meaningful solution. The issues include expansion to generate large numbers of cells, self-renewal to regulate the destiny of cord blood stem cells to repopulate the hematopoietic system, and multipotency of stem cells to generate the distinct cell types of an islet.

Energy-efficient neural information processing in individual neurons and neuronal networks.

PubMed

Yu, Lianchun; Yu, Yuguo

2017-11-01

Brains are composed of networks of an enormous number of neurons interconnected with synapses. Neural information is carried by the electrical signals within neurons and the chemical signals among neurons. Generating these electrical and chemical signals is metabolically expensive. The fundamental issue raised here is whether brains have evolved efficient ways of developing an energy-efficient neural code from the molecular level to the circuit level. Here, we summarize the factors and biophysical mechanisms that could contribute to the energy-efficient neural code for processing input signals. The factors range from ion channel kinetics, body temperature, axonal propagation of action potentials, low-probability release of synaptic neurotransmitters, optimal input and noise, the size of neurons and neuronal clusters, excitation/inhibition balance, coding strategy, cortical wiring, and the organization of functional connectivity. Both experimental and computational evidence suggests that neural systems may use these factors to maximize the efficiency of energy consumption in processing neural signals. Studies indicate that efficient energy utilization may be universal in neuronal systems as an evolutionary consequence of the pressure of limited energy. As a result, neuronal connections may be wired in a highly economical manner to lower energy costs and space. Individual neurons within a network may encode independent stimulus components to allow a minimal number of neurons to represent whole stimulus characteristics efficiently. This basic principle may fundamentally change our view of how billions of neurons organize themselves into complex circuits to operate and generate the most powerful intelligent cognition in nature. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

A pivotal role for reductive methylation in the de novo crystallization of a ternary complex composed of Yersinia pestis virulence factors YopN, SycN and YscB.

PubMed

Schubot, Florian D; Waugh, David S

2004-11-01

Structural studies of a ternary complex composed of the Yersina pestis virulence factors YopN, SycN and YscB were initially hampered by poor solubility of the individual proteins. Co-expression of all three proteins in Escherichia coli yielded a well behaved complex, but this sample proved to be recalcitrant to crystallization. As crystallization efforts remained fruitless, even after the proteolysis-guided engineering of a truncated YopN polypeptide, reductive methylation of lysine residues was employed to alter the surface properties of the complex. The methylated complex yielded crystals that diffracted X-rays to a maximal resolution of 1.8 A. The potential utility of reductive methylation as a remedial strategy for high-throughput structural biology was further underscored by the successful modification of a selenomethionine-substituted sample.

Dynamic positioning configuration and its first-order optimization

NASA Astrophysics Data System (ADS)

Xue, Shuqiang; Yang, Yuanxi; Dang, Yamin; Chen, Wu

2014-02-01

Traditional geodetic network optimization deals with static and discrete control points. The modern space geodetic network is, on the other hand, composed of moving control points in space (satellites) and on the Earth (ground stations). The network configuration composed of these facilities is essentially dynamic and continuous. Moreover, besides the position parameter which needs to be estimated, other geophysical information or signals can also be extracted from the continuous observations. The dynamic (continuous) configuration of the space network determines whether a particular frequency of signals can be identified by this system. In this paper, we employ the functional analysis and graph theory to study the dynamic configuration of space geodetic networks, and mainly focus on the optimal estimation of the position and clock-offset parameters. The principle of the D-optimization is introduced in the Hilbert space after the concept of the traditional discrete configuration is generalized from the finite space to the infinite space. It shows that the D-optimization developed in the discrete optimization is still valid in the dynamic configuration optimization, and this is attributed to the natural generalization of least squares from the Euclidean space to the Hilbert space. Then, we introduce the principle of D-optimality invariance under the combination operation and rotation operation, and propose some D-optimal simplex dynamic configurations: (1) (Semi) circular configuration in 2-dimensional space; (2) the D-optimal cone configuration and D-optimal helical configuration which is close to the GPS constellation in 3-dimensional space. The initial design of GPS constellation can be approximately treated as a combination of 24 D-optimal helixes by properly adjusting the ascending node of different satellites to realize a so-called Walker constellation. In the case of estimating the receiver clock-offset parameter, we show that the circular configuration, the symmetrical cone configuration and helical curve configuration are still D-optimal. It shows that the given total observation time determines the optimal frequency (repeatability) of moving known points and vice versa, and one way to improve the repeatability is to increase the rotational speed. Under the Newton's law of motion, the frequency of satellite motion determines the orbital altitude. Furthermore, we study three kinds of complex dynamic configurations, one of which is the combination of D-optimal cone configurations and a so-called Walker constellation composed of D-optimal helical configuration, the other is the nested cone configuration composed of n cones, and the last is the nested helical configuration composed of n orbital planes. It shows that an effective way to achieve high coverage is to employ the configuration composed of a certain number of moving known points instead of the simplex configuration (such as D-optimal helical configuration), and one can use the D-optimal simplex solutions or D-optimal complex configurations in any combination to achieve powerful configurations with flexile coverage and flexile repeatability. Alternately, how to optimally generate and assess the discrete configurations sampled from the continuous one is discussed. The proposed configuration optimization framework has taken the well-known regular polygons (such as equilateral triangle and quadrangular) in two-dimensional space and regular polyhedrons (regular tetrahedron, cube, regular octahedron, regular icosahedron, or regular dodecahedron) into account. It shows that the conclusions made by the proposed technique are more general and no longer limited by different sampling schemes. By the conditional equation of D-optimal nested helical configuration, the relevance issues of GNSS constellation optimization are solved and some examples are performed by GPS constellation to verify the validation of the newly proposed optimization technique. The proposed technique is potentially helpful in maintenance and quadratic optimization of single GNSS of which the orbital inclination and the orbital altitude change under the precession, as well as in optimally nesting GNSSs to perform global homogeneous coverage of the Earth.

Optimization of the imaging response of scanning microwave microscopy measurements

NASA Astrophysics Data System (ADS)

Sardi, G. M.; Lucibello, A.; Kasper, M.; Gramse, G.; Proietti, E.; Kienberger, F.; Marcelli, R.

2015-07-01

In this work, we present the analytical modeling and preliminary experimental results for the choice of the optimal frequencies when performing amplitude and phase measurements with a scanning microwave microscope. In particular, the analysis is related to the reflection mode operation of the instrument, i.e., the acquisition of the complex reflection coefficient data, usually referred as S11. The studied configuration is composed of an atomic force microscope with a microwave matched nanometric cantilever probe tip, connected by a λ/2 coaxial cable resonator to a vector network analyzer. The set-up is provided by Keysight Technologies. As a peculiar result, the optimal frequencies, where the maximum sensitivity is achieved, are different for the amplitude and for the phase signals. The analysis is focused on measurements of dielectric samples, like semiconductor devices, textile pieces, and biological specimens.

Activation of Drosophila hemocyte motility by the ecdysone hormone

PubMed Central

Sampson, Christopher J.; Amin, Unum; Couso, Juan-Pablo

2013-01-01

Summary Drosophila hemocytes compose the cellular arm of the fly's innate immune system. Plasmatocytes, putative homologues to mammalian macrophages, represent ∼95% of the migratory hemocyte population in circulation and are responsible for the phagocytosis of bacteria and apoptotic tissues that arise during metamorphosis. It is not known as to how hemocytes become activated from a sessile state in response to such infectious and developmental cues, although the hormone ecdysone has been suggested as the signal that shifts hemocyte behaviour from quiescent to migratory at metamorphosis. Here, we corroborate this hypothesis by showing the activation of hemocyte motility by ecdysone. We induce motile behaviour in larval hemocytes by culturing them with 20-hydroxyecdysone ex vivo. Moreover, we also determine that motile cell behaviour requires the ecdysone receptor complex and leads to asymmetrical redistribution of both actin and tubulin cytoskeleton. PMID:24285708

Subunit stoichiometry of the CNG channel of rod photoreceptors.

PubMed

Weitz, Dietmar; Ficek, Nicole; Kremmer, Elisabeth; Bauer, Paul J; Kaupp, U Benjamin

2002-12-05

Cyclic nucleotide-gated (CNG) channels play a central role in the conversion of sensory stimuli into electrical signals. CNG channels form heterooligomeric complexes built of A and B subunits. Here, we study the subunit stoichiometry of the native rod CNG channel by chemical crosslinking. The apparent molecular weight (M(w)) of each crosslink product was determined by SDS-PAGE, and its composition was analyzed by Western blotting using antibodies specific for the A1 or B1 subunit. The number of crosslink products and their M(w) as well as the immunological identification of A1 and B1 subunits in the crosslink products led us to conclude that the native rod CNG channel is a tetramer composed of three A1 and one B1 subunit. This is an example of violation of symmetry in tetrameric channels.

Dynamic pre-BCR homodimers fine-tune autonomous survival signals in B cell precursor acute lymphoblastic leukemia

PubMed Central

Erasmus, M. Frank; Matlawska-Wasowska, Ksenia; Kinjyo, Ichiko; Mahajan, Avanika; Winter, Stuart S.; Xu, Li; Horowitz, Michael; Lidke, Diane S.; Wilson, Bridget S.

2017-01-01

The pre-B cell receptor (pre-BCR) is an immature form of the BCR critical for early B lymphocyte development. It is composed of the membrane-bound immunoglobulin (Ig) heavy chain, surrogate light chain components, and the signaling subunits Igα and Igβ. We developed monovalent Quantum Dot (QD)-labeled probes specific for Igβ to study the behavior of pre-BCRs engaged in autonomous, ligand-independent signaling in live B cells. Single-particle tracking revealed that QD-labeled pre-BCRs engaged in transient, but frequent, homotypic interactions. Receptor motion was correlated at short separation distances, consistent with the formation of dimers and higher-order oligomers. Repeated encounters between diffusing pre-BCRs appeared to reflect transient co-confinement in plasma membrane domains. In human B cell precursor acute lymphoblastic leukemia (BCP-ALL) cells, we showed that frequent, short-lived, homotypic pre-BCR interactions stimulated survival signals, including expression of BCL6, which encodes a transcriptional repressor. These survival signals were blocked by inhibitory monovalent antigen-binding antibody fragments (Fabs) specific for the surrogate light chain components of the pre-BCR or by inhibitors of the tyrosine kinases Lyn and Syk. For comparison, we evaluated pre-BCR aggregation mediated by dimeric galectin-1, which has binding sites for carbohydrate and for the λ5 component of the surrogate light chain. Galectin-1 binding resulted in the formation of large, highly immobile pre-BCR aggregates, which was partially relieved by the addition of lactose to prevent the crosslinking of galectin-BCR complexes to other glycosylated membrane components. Analysis of the pre-BCR and its signaling partners suggested that they could be potential targets for combination therapy in BCP-ALL. PMID:27899526

When Bad Guys Become Good Ones: The Key Role of Reactive Oxygen Species and Nitric Oxide in the Plant Responses to Abiotic Stress

PubMed Central

Farnese, Fernanda S.; Menezes-Silva, Paulo E.; Gusman, Grasielle S.; Oliveira, Juraci A.

2016-01-01

The natural environment of plants is composed of a complex set of abiotic stresses and their ability to respond to these stresses is highly flexible and finely balanced through the interaction between signaling molecules. In this review, we highlight the integrated action between reactive oxygen species (ROS) and reactive nitrogen species (RNS), particularly nitric oxide (NO), involved in the acclimation to different abiotic stresses. Under stressful conditions, the biosynthesis transport and the metabolism of ROS and NO influence plant response mechanisms. The enzymes involved in ROS and NO synthesis and scavenging can be found in different cells compartments and their temporal and spatial locations are determinant for signaling mechanisms. Both ROS and NO are involved in long distances signaling (ROS wave and GSNO transport), promoting an acquired systemic acclimation to abiotic stresses. The mechanisms of abiotic stresses response triggered by ROS and NO involve some general steps, as the enhancement of antioxidant systems, but also stress-specific mechanisms, according to the stress type (drought, hypoxia, heavy metals, etc.), and demand the interaction with other signaling molecules, such as MAPK, plant hormones, and calcium. The transduction of ROS and NO bioactivity involves post-translational modifications of proteins, particularly S-glutathionylation for ROS, and S-nitrosylation for NO. These changes may alter the activity, stability, and interaction with other molecules or subcellular location of proteins, changing the entire cell dynamics and contributing to the maintenance of homeostasis. However, despite the recent advances about the roles of ROS and NO in signaling cascades, many challenges remain, and future studies focusing on the signaling of these molecules in planta are still necessary. PMID:27148300

When Bad Guys Become Good Ones: The Key Role of Reactive Oxygen Species and Nitric Oxide in the Plant Responses to Abiotic Stress.

PubMed

Farnese, Fernanda S; Menezes-Silva, Paulo E; Gusman, Grasielle S; Oliveira, Juraci A

2016-01-01

The natural environment of plants is composed of a complex set of abiotic stresses and their ability to respond to these stresses is highly flexible and finely balanced through the interaction between signaling molecules. In this review, we highlight the integrated action between reactive oxygen species (ROS) and reactive nitrogen species (RNS), particularly nitric oxide (NO), involved in the acclimation to different abiotic stresses. Under stressful conditions, the biosynthesis transport and the metabolism of ROS and NO influence plant response mechanisms. The enzymes involved in ROS and NO synthesis and scavenging can be found in different cells compartments and their temporal and spatial locations are determinant for signaling mechanisms. Both ROS and NO are involved in long distances signaling (ROS wave and GSNO transport), promoting an acquired systemic acclimation to abiotic stresses. The mechanisms of abiotic stresses response triggered by ROS and NO involve some general steps, as the enhancement of antioxidant systems, but also stress-specific mechanisms, according to the stress type (drought, hypoxia, heavy metals, etc.), and demand the interaction with other signaling molecules, such as MAPK, plant hormones, and calcium. The transduction of ROS and NO bioactivity involves post-translational modifications of proteins, particularly S-glutathionylation for ROS, and S-nitrosylation for NO. These changes may alter the activity, stability, and interaction with other molecules or subcellular location of proteins, changing the entire cell dynamics and contributing to the maintenance of homeostasis. However, despite the recent advances about the roles of ROS and NO in signaling cascades, many challenges remain, and future studies focusing on the signaling of these molecules in planta are still necessary.

Probing Teachers' Lesson Planning: Promoting Metacognition

ERIC Educational Resources Information Center

Eilam, Billie

2017-01-01

Classrooms are complex systems, with dynamic interactions of different kinds among their composing varied elements. Such complex interactions lead to the system's unpredictable emergent learning behaviors. To support teachers' lesson planning and monitoring in the complex environment of classrooms, the present article examines the core…

Stability of kinetochore-microtubule attachment and the role of different KMN network components in Drosophila.

PubMed

Feijão, Tália; Afonso, Olga; Maia, André F; Sunkel, Claudio E

2013-10-01

Kinetochores bind spindle microtubules and also act as signaling centers that monitor this interaction. Defects in kinetochore assembly lead to chromosome missegregation and aneuploidy. The interaction between microtubules and chromosomes involves a conserved super-complex of proteins, known as the KNL1Mis12Ndc80 (KMN) network, composed by the KNL1 (Spc105), Mis12, and Ndc80 complexes. Previous studies indicate that all components of the network are required for kinetochore-microtubule attachment and all play relevant functions in chromosome congression, biorientation, and segregation. Here, we report a comparative study addressing the role of the different KMN components using dsRNA and in vivo fluorescence microscopy in Drosophila S2 cells allowing us to suggest that different KMN network components might perform different roles in chromosome segregation and the mitotic checkpoint signaling. Depletion of different components results in mostly lateral kinetochore-microtubule attachments that are relatively stable on depletion of Mis12 or Ndc80 but very unstable after Spc105 depletion. In vivo analysis on depletion of Mis12, Ndc80, and to some extent Spc105, shows that lateral kinetochore-microtubule interactions are still functional allowing poleward kinetochore movement. We also find that different KMN network components affect differently the localization of spindle assembly checkpoint (SAC) proteins at kinetochores. Depletion of Ndc80 and Spc105 abolishes the mitotic checkpoint, whereas depletion of Mis12 causes a delay in mitotic progression. Taken together, our results suggest that Mis12 and Ndc80 complexes help to properly orient microtubule attachment, whereas Spc105 plays a predominant role in the kinetochore-microtubule attachment as well as in the poleward movement of chromosomes, SAC response, and cell viability. Copyright © 2013 Wiley Periodicals, Inc.

Sedimentation of the mud belt along the coast of China from the mouth of the Yangtze (Changjiang) River to northern Taiwan Strait: An Source-to-Sink Perspective

NASA Astrophysics Data System (ADS)

Chien, C. C.; Liu, J. T.; Yang, R.; Huh, C. A.; Su, C. C.

2016-02-01

Sediments in the Taiwan Strait are originated from Mainland China and Taiwan. The China Coastal Current, influenced by the northeast monsoon in winter, becomes enhanced, which caries the sediments exported from the Yangtze River to the southern East China Sea and the Taiwan Strait along the Zhemin-Taiwan Strait mud belt. The sediment transport process is also influenced by tidal current and Kuroshio Branch Current and Taiwan Warm Current, making the seafloor sediment signals complex. This study used R/V Ocean Researcher V (Cruise 0032), to collect six box cores and three gravity cores along the Zhemin mud belt and the mud belt in northern Taiwan Strait in the winter of 2014. From the core samples, grain-size distribution, Multi-Sensor Core Logger, and 7Be activity were measured to investigate the sedimentation process along the mud belts. The box core taken at the mouth of the Changjiang- is composed of homogeneous clay and rich in shell fragments. The core off the mouth of Ou River is composed of homogeneous clay, but showing horizontal laminations. Near the Taishan Island off the coast of Zhejiang the core is consisted of a homogeneous sandy sediments that turned into clay. Off the mouth of the Min River the core consists of clay with shell fragments. Off the coast of the Wu River on the west coast of the Taiwan, the core is mainly composed of muddy sediments, which has the siltstone layers of oblique bedding. Off the mouth of Zhuoshui River in central Taiwan, the core is composed of sandy sediments. From the mouth of the Changhjiang, Zhemin mud belt, the northern Taiwan Strait mud belt, to the central Taiwan Strait, 7Be activity in the seafloor sediment indicates that the freshness of the terrigenous sediments decreased. The Mass Magnetic Susceptiblity (MSI) demonstrates that the terrigenous sediments decreased from north to south. The MSI signals in the core off the mouth of the Minjiang are different from those in the neighboring cores. This is suspected due to the convergence of sediments from the Changjiang and Taiwan. The particle sizes of the cores show that the sediment became coarser from the north to south. In the future the study will make use of 210Pbex, and other environmental and provenance such as water dynamic mechanism variables to explore the sediment source and sink patterns along with the Zhemin-Taiwan Strait mud belts.

Signaling pathways that regulate life and cell death: evolution of apoptosis in the context of self-defense.

PubMed

Muñoz-Pinedo, Cristina

2012-01-01

Programmed Cell Death is essential for the life cycle of many organisms. Cell death in multicellular organisms can occur as a consequence of massive damage (necrosis) or in a controlled form, through engagement of diverse biochemical programs. The best well known form of programmed cell death is apoptosis. Apoptosis occurs in animals as a consequence of a variety of stimuli including stress and social signals and it plays essential roles in morphogenesis and immune defense. The machinery of apoptosis is well conserved among animals and it is composed of caspases (the proteases which execute cell death), adapter proteins (caspase activators), Bcl-2 family proteins and Inhibitor of Apoptosis Proteins (IAPs). We will describe in this chapter the main apoptotic pathways in animals: the extrinsic (death receptor-mediated), the intrinsic/mitochondrial and the Granzyme B pathway. Other forms of non-apoptotic Programmed Cell Death which occur in animals will also be discussed. We will summarize the current knowledge about apoptotic-like and other forms of cell death in other organisms such as plants and protists.Additionally, we will discuss the hypothesis that apoptosis originated as part of a host defense mechanism. We will explore the similarities between the protein complexes which mediate apoptosis (apoptosomes) and complexes involved in immunity: inflammasomes. Additional functions of apoptotic proteins related to immune function will be summarized, in an effort to explore the evolutionary origins of cell death.

Measurement of angular velocity in the perception of rotation.

PubMed

Barraza, José F; Grzywacz, Norberto M

2002-09-01

Humans are sensitive to the parameters of translational motion, namely, direction and speed. At the same time, people have special mechanisms to deal with more complex motions, such as rotations and expansions. One wonders whether people may also be sensitive to the parameters of these complex motions. Here, we report on a series of experiments that explore whether human subjects can use angular velocity to evaluate how fast a rotational motion is. In four experiments, subjects were required to perform a task of speed-of-rotation discrimination by comparing two annuli of different radii in a temporal 2AFC paradigm. Results showed that humans could rely on a sensitive measurement of angular velocity to perform this discrimination task. This was especially true when the quality of the rotational signal was high (given by the number of dots composing the annulus). When the signal quality decreased, a bias towards linear velocity of 5-80% appeared, suggesting the existence of separate mechanisms for angular and linear velocity. This bias was independent from the reference radius. Finally, we asked whether the measurement of angular velocity required a rigid rotation, that is, whether the visual system makes only one global estimate of angular velocity. For this purpose, a random-dot disk was built such that all the dots were rotating with the same tangential speed, irrespectively of radius. Results showed that subjects do not estimate a unique global angular velocity, but that they perceive a non-rigid disk, with angular velocity falling inversely proportionally with radius.

Analysis of the Impedance Resonance of Piezoelectric Multi-Fiber Composite Stacks

NASA Technical Reports Server (NTRS)

Sherrit, S.; Djrbashian, A.; Bradford, S C

2013-01-01

Multi-Fiber CompositesTM (MFC's) produced by Smart Materials Corp behave essentially like thin planar stacks where each piezoelectric layer is composed of a multitude of fibers. We investigate the suitability of using previously published inversion techniques for the impedance resonances of monolithic co-fired piezoelectric stacks to the MFCTM to determine the complex material constants from the impedance data. The impedance equations examined in this paper are those based on the derivation. The utility of resonance techniques to invert the impedance data to determine the small signal complex material constants are presented for a series of MFC's. The technique was applied to actuators with different geometries and the real coefficients were determined to be similar within changes of the boundary conditions due to change of geometry. The scatter in the imaginary coefficient was found to be larger. The technique was also applied to the same actuator type but manufactured in different batches with some design changes in the non active portion of the actuator and differences in the dielectric and the electromechanical coupling between the two batches were easily measureable. It is interesting to note that strain predicted by small signal impedance analysis is much lower than high field stains. Since the model is based on material properties rather than circuit constants, it could be used for the direct evaluation of specific aging or degradation mechanisms in the actuator as well as batch sorting and adjustment of manufacturing processes.

Detailed investigation of Long-Period activity at Campi Flegrei by Convolutive Independent Component Analysis

NASA Astrophysics Data System (ADS)

Capuano, P.; De Lauro, E.; De Martino, S.; Falanga, M.

2016-04-01

This work is devoted to the analysis of seismic signals continuously recorded at Campi Flegrei Caldera (Italy) during the entire year 2006. The radiation pattern associated with the Long-Period energy release is investigated. We adopt an innovative Independent Component Analysis algorithm for convolutive seismic series adapted and improved to give automatic procedures for detecting seismic events often buried in the high-level ambient noise. The extracted waveforms characterized by an improved signal-to-noise ratio allows the recognition of Long-Period precursors, evidencing that the seismic activity accompanying the mini-uplift crisis (in 2006), which climaxed in the three days from 26-28 October, had already started at the beginning of the month of October and lasted until mid of November. Hence, a more complete seismic catalog is then provided which can be used to properly quantify the seismic energy release. To better ground our results, we first check the robustness of the method by comparing it with other blind source separation methods based on higher order statistics; secondly, we reconstruct the radiation patterns of the extracted Long-Period events in order to link the individuated signals directly to the sources. We take advantage from Convolutive Independent Component Analysis that provides basic signals along the three directions of motion so that a direct polarization analysis can be performed with no other filtering procedures. We show that the extracted signals are mainly composed of P waves with radial polarization pointing to the seismic source of the main LP swarm, i.e. a small area in the Solfatara, also in the case of the small-events, that both precede and follow the main activity. From a dynamical point of view, they can be described by two degrees of freedom, indicating a low-level of complexity associated with the vibrations from a superficial hydrothermal system. Our results allow us to move towards a full description of the complexity of the source, which can be used, by means of the small-intensity precursors, for hazard-model development and forecast-model testing, showing an illustrative example of the applicability of the CICA method to regions with low seismicity in high ambient noise.

Cancer cell death induced by phosphine gold(I) compounds targeting thioredoxin reductase.

PubMed

Gandin, Valentina; Fernandes, Aristi Potamitou; Rigobello, Maria Pia; Dani, Barbara; Sorrentino, Francesca; Tisato, Francesco; Björnstedt, Mikael; Bindoli, Alberto; Sturaro, Alberto; Rella, Rocco; Marzano, Cristina

2010-01-15

The thioredoxin system, composed of thioredoxin reductase (TrxR), thioredoxin (Trx), and NADPH (nicotinamide adenine dinucleotide phosphate), plays a central role in regulating cellular redox homeostasis and signaling pathways. TrxR, overexpressed in many tumor cells and contributing to drug resistance, has emerged as a new target for anticancer drugs. Gold complexes have been validated as potent TrxR inhibitors in vitro in the nanomolar range. In order to obtain potent and selective TrxR inhibitors, we have synthesized a series of linear, 'auranofin-like' gold(I) complexes all containing the [Au(PEt(3))](+) synthon and the ligands: Cl(-), Br(-), cyanate, thiocyanate, ethylxanthate, diethyldithiocarbamate and thiourea. Phosphine gold(I) complexes efficiently inhibited cytosolic and mitochondrial TrxR at concentrations that did not affect the two related oxidoreductases glutathione reductase (GR) and glutathione peroxidase (GPx). The inhibitory effect of the redox proteins was also observed intracellularly in cancer cells pretreated with gold(I) complexes. Gold(I) compounds were found to induce antiproliferative effects towards several human cancer cells some of which endowed with cisplatin or multidrug resistance. In addition, they were able to activate caspase-3 and induce apoptosis observed as nucleosome formation and sub-G1 cell accumulation. The complexes with thiocyanate and xanthate ligands were particularly effective in inhibiting thioredoxin reductase and inducing apoptosis. Pharmacodynamic studies in human ovarian cancer cells allowed for the correlation of intracellular drug accumulation with TrxR inhibition that leads to the induction of apoptosis via the mitochondrial pathway.

Complex network approach to classifying classical piano compositions

NASA Astrophysics Data System (ADS)

Xin, Chen; Zhang, Huishu; Huang, Jiping

2016-10-01

Complex network has been regarded as a useful tool handling systems with vague interactions. Hence, numerous applications have arised. In this paper we construct complex networks for 770 classical piano compositions of Mozart, Beethoven and Chopin based on musical note pitches and lengths. We find prominent distinctions among network edges of different composers. Some stylized facts can be explained by such parameters of network structures and topologies. Further, we propose two classification methods for music styles and genres according to the discovered distinctions. These methods are easy to implement and the results are sound. This work suggests that complex network could be a decent way to analyze the characteristics of musical notes, since it could provide a deep view into understanding of the relationships among notes in musical compositions and evidence for classification of different composers, styles and genres of music.

The RPAP3-Cterminal domain identifies R2TP-like quaternary chaperones.

PubMed

Maurizy, Chloé; Quinternet, Marc; Abel, Yoann; Verheggen, Céline; Santo, Paulo E; Bourguet, Maxime; C F Paiva, Ana; Bragantini, Benoît; Chagot, Marie-Eve; Robert, Marie-Cécile; Abeza, Claire; Fabre, Philippe; Fort, Philippe; Vandermoere, Franck; M F Sousa, Pedro; Rain, Jean-Christophe; Charpentier, Bruno; Cianférani, Sarah; Bandeiras, Tiago M; Pradet-Balade, Bérengère; Manival, Xavier; Bertrand, Edouard

2018-05-29

R2TP is an HSP90 co-chaperone that assembles important macro-molecular machineries. It is composed of an RPAP3-PIH1D1 heterodimer, which binds the two essential AAA+ATPases RUVBL1/RUVBL2. Here, we resolve the structure of the conserved C-terminal domain of RPAP3, and we show that it directly binds RUVBL1/RUVBL2 hexamers. The human genome encodes two other proteins bearing RPAP3-C-terminal-like domains and three containing PIH-like domains. Systematic interaction analyses show that one RPAP3-like protein, SPAG1, binds PIH1D2 and RUVBL1/2 to form an R2TP-like complex termed R2SP. This co-chaperone is enriched in testis and among 68 of the potential clients identified, some are expressed in testis and others are ubiquitous. One substrate is liprin-α2, which organizes large signaling complexes. Remarkably, R2SP is required for liprin-α2 expression and for the assembly of liprin-α2 complexes, indicating that R2SP functions in quaternary protein folding. Effects are stronger at 32 °C, suggesting that R2SP could help compensating the lower temperate of testis.

High-Resolution 3T MR Imaging of the Triangular Fibrocartilage Complex

PubMed Central

von Borstel, Donald; Wang, Michael; Small, Kirstin; Nozaki, Taiki; Yoshioka, Hiroshi

2017-01-01

This study is intended as a review of 3Tesla (T) magnetic resonance (MR) imaging of the triangular fibrocartilage complex (TFCC). The recent advances in MR imaging, which includes high field strength magnets, multi-channel coils, and isotropic 3-dimensional (3D) sequences have enabled the visualization of precise TFCC anatomy with high spatial and contrast resolution. In addition to the routine wrist protocol, there are specific techniques used to optimize 3T imaging of the wrist; including driven equilibrium sequence (DRIVE), parallel imaging, and 3D imaging. The coil choice for 3T imaging of the wrist depends on a number of variables, and the proper coil design selection is critical for high-resolution wrist imaging with high signal and contrast-to-noise ratio. The TFCC is a complex structure and is composed of the articular disc (disc proper), the triangular ligament, the dorsal and volar radioulnar ligaments, the meniscus homologue, the ulnar collateral ligament (UCL), the extensor carpi ulnaris (ECU) tendon sheath, and the ulnolunate and ulnotriquetral ligaments. The Palmer classification categorizes TFCC lesions as traumatic (type 1) or degenerative (type 2). In this review article, we present clinical high-resolution MR images of normal TFCC anatomy and TFCC injuries with this classification system. PMID:27535592

High-Resolution 3T MR Imaging of the Triangular Fibrocartilage Complex.

PubMed

von Borstel, Donald; Wang, Michael; Small, Kirstin; Nozaki, Taiki; Yoshioka, Hiroshi

2017-01-10

This study is intended as a review of 3Tesla (T) magnetic resonance (MR) imaging of the triangular fibrocartilage complex (TFCC). The recent advances in MR imaging, which includes high field strength magnets, multi-channel coils, and isotropic 3-dimensional (3D) sequences have enabled the visualization of precise TFCC anatomy with high spatial and contrast resolution. In addition to the routine wrist protocol, there are specific techniques used to optimize 3T imaging of the wrist; including driven equilibrium sequence (DRIVE), parallel imaging, and 3D imaging. The coil choice for 3T imaging of the wrist depends on a number of variables, and the proper coil design selection is critical for high-resolution wrist imaging with high signal and contrast-to-noise ratio. The TFCC is a complex structure and is composed of the articular disc (disc proper), the triangular ligament, the dorsal and volar radioulnar ligaments, the meniscus homologue, the ulnar collateral ligament (UCL), the extensor carpi ulnaris (ECU) tendon sheath, and the ulnolunate and ulnotriquetral ligaments. The Palmer classification categorizes TFCC lesions as traumatic (type 1) or degenerative (type 2). In this review article, we present clinical high-resolution MR images of normal TFCC anatomy and TFCC injuries with this classification system.

Acoustic surface perception from naturally occurring step sounds of a dexterous hexapod robot

NASA Astrophysics Data System (ADS)

Cuneyitoglu Ozkul, Mine; Saranli, Afsar; Yazicioglu, Yigit

2013-10-01

Legged robots that exhibit dynamic dexterity naturally interact with the surface to generate complex acoustic signals carrying rich information on the surface as well as the robot platform itself. However, the nature of a legged robot, which is a complex, hybrid dynamic system, renders the more common approach of model-based system identification impractical. The present paper focuses on acoustic surface identification and proposes a non-model-based analysis and classification approach adopted from the speech processing literature. A novel feature set composed of spectral band energies augmented by their vector time derivatives and time-domain averaged zero crossing rate is proposed. Using a multi-dimensional vector classifier, these features carry enough information to accurately classify a range of commonly occurring indoor and outdoor surfaces without using of any mechanical system model. A comparative experimental study is carried out and classification performance and computational complexity are characterized. Different feature combinations, classifiers and changes in critical design parameters are investigated. A realistic and representative acoustic data set is collected with the robot moving at different speeds on a number of surfaces. The study demonstrates promising performance of this non-model-based approach, even in an acoustically uncontrolled environment. The approach also has good chance of performing in real-time.

The Cognitive Architecture for Chaining of Two Mental Operations

ERIC Educational Resources Information Center

Sackur, Jerome; Dehaene, Stanislas

2009-01-01

A simple view, which dates back to Turing, proposes that complex cognitive operations are composed of serially arranged elementary operations, each passing intermediate results to the next. However, whether and how such serial processing is achieved with a brain composed of massively parallel processors, remains an open question. Here, we study…

Novel approach of signal normalization for depth profile of cultural heritage materials

NASA Astrophysics Data System (ADS)

Syvilay, D.; Detalle, V.; Wilkie-Chancellier, N.; Texier, A.; Martinez, L.; Serfaty, S.

2017-01-01

The investigation of cultural heritage materials is always complex and specific because unique. Materials are most often heterogeneous and organized in several layers such as mural paintings or corrosion products. The characterization of a complete artwork's stratigraphy is actually one of the questions of science conservation. Indeed, the knowledge of these layers allows completing the history of the work of art and a better understanding of alteration processes in order to set up an appropriate conservation action. The LIBS technique has been employed to study the stratigraphy of an artwork thanks to the ablation laser. However, as we know, atomic information could be insufficient to characterize two materials composed by the same based elements. Therefore, an additional molecular analysis, like Raman spectroscopy; is sometimes necessary for a better identification of the material in particular for organic coatings in cultural heritage. We suggest in this study to use Standard Normal Variate (SNV) as a common normalization for different kinds of spectra (LIBS and Raman spectroscopy) combined with a 3D colour representation for stratigraphic identification of the different layers composing the complex material from artwork. So in this investigation, the SNV method will be applied on LIBS and Raman spectra but also on baseline Raman spectra often considering as nuisance. The aim of this study is to demonstrate the versatility of SNV applied on varied spectra like LIBS, Raman spectra as well as the luminescence background. This original work considers the SNV with a 3D colour representation as a probable new perspective for an easy recognition of a structure layered with a direct overview of the depth profile of the artwork.

Buried plastic scintillator muon telescope

NASA Astrophysics Data System (ADS)

Sanchez, F.; Medina-Tanco, G.A.; D'Olivo, J.C.; Paic, G.; Patino Salazar, M.E.; Nahmad-Achar, E.; Valdes Galicia, J.F.; Sandoval, A.; Alfaro Molina, R.; Salazar Ibarguen, H.; Diozcora Vargas Trevino, M.A.; Vergara Limon, S.; Villasenor, L.M.

Muon telescopes can have several applications, ranging from astrophysical to solar-terrestrial interaction studies, and fundamental particle physics. We show the design parameters, characterization and end-to-end simulations of a detector composed by a set of three parallel dual-layer scintillator planes, buried at fix depths ranging from 0.30 m to 3 m. Each layer is 4 m2 and is composed by 50 rectangular pixels of 4cm x 2 m, oriented at a 90 deg angle with respect to its companion layer. The scintillators are MINOS extruded polystyrene strips with two Bicron wavelength shifting fibers mounted on machined grooves. Scintillation light is collected by multi-anode PMTs of 64 pixels, accommodating two fibers per pixel. The front-end electronics has a time resolution of 7.5 nsec. Any strip signal above threshold opens a GPS-tagged 2 micro-seconds data collection window. All data, including signal and background, are saved to hard disk. Separation of extensive air shower signals from secondary cosmic-ray background muons and electrons is done offline using the GPS-tagged threefold coincidence signal from surface water cerenkov detectors located nearby in a triangular array. Cosmic-ray showers above 6 PeV are selected. The data acquisition system is designed to keep both, background and signals from extensive air showers for a detailed offline data.

Complex extreme learning machine applications in terahertz pulsed signals feature sets.

PubMed

Yin, X-X; Hadjiloucas, S; Zhang, Y

2014-11-01

This paper presents a novel approach to the automatic classification of very large data sets composed of terahertz pulse transient signals, highlighting their potential use in biochemical, biomedical, pharmaceutical and security applications. Two different types of THz spectra are considered in the classification process. Firstly a binary classification study of poly-A and poly-C ribonucleic acid samples is performed. This is then contrasted with a difficult multi-class classification problem of spectra from six different powder samples that although have fairly indistinguishable features in the optical spectrum, they also possess a few discernable spectral features in the terahertz part of the spectrum. Classification is performed using a complex-valued extreme learning machine algorithm that takes into account features in both the amplitude as well as the phase of the recorded spectra. Classification speed and accuracy are contrasted with that achieved using a support vector machine classifier. The study systematically compares the classifier performance achieved after adopting different Gaussian kernels when separating amplitude and phase signatures. The two signatures are presented as feature vectors for both training and testing purposes. The study confirms the utility of complex-valued extreme learning machine algorithms for classification of the very large data sets generated with current terahertz imaging spectrometers. The classifier can take into consideration heterogeneous layers within an object as would be required within a tomographic setting and is sufficiently robust to detect patterns hidden inside noisy terahertz data sets. The proposed study opens up the opportunity for the establishment of complex-valued extreme learning machine algorithms as new chemometric tools that will assist the wider proliferation of terahertz sensing technology for chemical sensing, quality control, security screening and clinic diagnosis. Furthermore, the proposed algorithm should also be very useful in other applications requiring the classification of very large datasets. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Frequency domain laser velocimeter signal processor: A new signal processing scheme

NASA Technical Reports Server (NTRS)

Meyers, James F.; Clemmons, James I., Jr.

1987-01-01

A new scheme for processing signals from laser velocimeter systems is described. The technique utilizes the capabilities of advanced digital electronics to yield a smart instrument that is able to configure itself, based on the characteristics of the input signals, for optimum measurement accuracy. The signal processor is composed of a high-speed 2-bit transient recorder for signal capture and a combination of adaptive digital filters with energy and/or zero crossing detection signal processing. The system is designed to accept signals with frequencies up to 100 MHz with standard deviations up to 20 percent of the average signal frequency. Results from comparative simulation studies indicate measurement accuracies 2.5 times better than with a high-speed burst counter, from signals with as few as 150 photons per burst.

Denoising of chaotic signal using independent component analysis and empirical mode decomposition with circulate translating

NASA Astrophysics Data System (ADS)

Wen-Bo, Wang; Xiao-Dong, Zhang; Yuchan, Chang; Xiang-Li, Wang; Zhao, Wang; Xi, Chen; Lei, Zheng

2016-01-01

In this paper, a new method to reduce noises within chaotic signals based on ICA (independent component analysis) and EMD (empirical mode decomposition) is proposed. The basic idea is decomposing chaotic signals and constructing multidimensional input vectors, firstly, on the base of EMD and its translation invariance. Secondly, it makes the independent component analysis on the input vectors, which means that a self adapting denoising is carried out for the intrinsic mode functions (IMFs) of chaotic signals. Finally, all IMFs compose the new denoised chaotic signal. Experiments on the Lorenz chaotic signal composed of different Gaussian noises and the monthly observed chaotic sequence on sunspots were put into practice. The results proved that the method proposed in this paper is effective in denoising of chaotic signals. Moreover, it can correct the center point in the phase space effectively, which makes it approach the real track of the chaotic attractor. Project supported by the National Science and Technology, China (Grant No. 2012BAJ15B04), the National Natural Science Foundation of China (Grant Nos. 41071270 and 61473213), the Natural Science Foundation of Hubei Province, China (Grant No. 2015CFB424), the State Key Laboratory Foundation of Satellite Ocean Environment Dynamics, China (Grant No. SOED1405), the Hubei Provincial Key Laboratory Foundation of Metallurgical Industry Process System Science, China (Grant No. Z201303), and the Hubei Key Laboratory Foundation of Transportation Internet of Things, Wuhan University of Technology, China (Grant No.2015III015-B02).

Characterizing and differentiating task-based and resting state fMRI signals via two-stage sparse representations.

PubMed

Zhang, Shu; Li, Xiang; Lv, Jinglei; Jiang, Xi; Guo, Lei; Liu, Tianming

2016-03-01

A relatively underexplored question in fMRI is whether there are intrinsic differences in terms of signal composition patterns that can effectively characterize and differentiate task-based or resting state fMRI (tfMRI or rsfMRI) signals. In this paper, we propose a novel two-stage sparse representation framework to examine the fundamental difference between tfMRI and rsfMRI signals. Specifically, in the first stage, the whole-brain tfMRI or rsfMRI signals of each subject were composed into a big data matrix, which was then factorized into a subject-specific dictionary matrix and a weight coefficient matrix for sparse representation. In the second stage, all of the dictionary matrices from both tfMRI/rsfMRI data across multiple subjects were composed into another big data-matrix, which was further sparsely represented by a cross-subjects common dictionary and a weight matrix. This framework has been applied on the recently publicly released Human Connectome Project (HCP) fMRI data and experimental results revealed that there are distinctive and descriptive atoms in the cross-subjects common dictionary that can effectively characterize and differentiate tfMRI and rsfMRI signals, achieving 100% classification accuracy. Moreover, our methods and results can be meaningfully interpreted, e.g., the well-known default mode network (DMN) activities can be recovered from the very noisy and heterogeneous aggregated big-data of tfMRI and rsfMRI signals across all subjects in HCP Q1 release.

The Good, the Bad and the Ugly? The Dynamic Interplay between Educational Practice, Policy and Research

ERIC Educational Resources Information Center

Van Geert, Paul; Steenbeek, Henderien

2014-01-01

The notion of complexity--as in "education is a complex system"--has two different meanings. On the one hand, there is the epistemic connotation, with "Complex" meaning "difficult to understand, hard to control". On the other hand, complex has a technical meaning, referring to systems composed of many interacting…

Successful COG8 and PDF overlap is mediated by alterations in splicing and polyadenylation signals.

PubMed

Pereira-Castro, Isabel; Quental, Rita; da Costa, Luís T; Amorim, António; Azevedo, Luisa

2012-02-01

Although gene-free areas compose the great majority of eukaryotic genomes, a significant fraction of genes overlaps, i.e., unique nucleotide sequences are part of more than one transcription unit. In this work, the evolutionary history and origin of a same-strand gene overlap is dissected through the analysis of COG8 (component of oligomeric Golgi complex 8) and PDF (peptide deformylase). Comparative genomic surveys reveal that the relative locations of these two genes have been changing over the last 445 million years from distinct chromosomal locations in fish to overlapping in rodents and primates, indicating that the overlap between these genes precedes their divergence. The overlap between the two genes was initiated by the gain of a novel splice donor site between the COG8 stop codon and PDF initiation codon. Splicing is accomplished by the use of the PDF acceptor, leading COG8 to share the 3'end with PDF. In primates, loss of the ancestral polyadenylation signal for COG8 makes the overlap between COG8 and PDF mandatory, while in mouse and rat concurrent overlapping and non-overlapping Cog8 transcripts exist. Altogether, we demonstrate that the origin, evolution and preservation of the COG8/PDF same-strand overlap follow similar mechanistic steps as those documented for antisense overlaps where gain and/or loss of splice sites and polyadenylation signals seems to drive the process.

Acoustic analog computing based on a reflective metasurface with decoupled modulation of phase and amplitude

NASA Astrophysics Data System (ADS)

Zuo, Shu-Yu; Tian, Ye; Wei, Qi; Cheng, Ying; Liu, Xiao-Jun

2018-03-01

The use of metasurfaces has allowed the provision of a variety of functionalities by ultrathin structures, paving the way toward novel highly compact analog computing devices. Here, we conceptually realize analog computing using an acoustic reflective computational metasurface (RCM) that can independently manipulate the reflection phase and amplitude of an incident acoustic signal. This RCM is composed of coating unit cells and perforated panels, where the first can tune the transmission phase within the full range of 2π and the second can adjust the reflection amplitude in the range of 0-1. We show that this RCM can achieve arbitrary reflection phase and amplitude and can be used to realize a unique linear spatially invariant transfer function. Using the spatial Fourier transform (FT), an acoustic analog computing (AAC) system is proposed based on the RCM together with a focusing lens. Based on numerical simulations, we demonstrate that this AAC system can perform mathematical operations such as spatial differentiation, integration, and convolution on an incident acoustic signal. The proposed system has low complexity and reduced size because the RCM is able to individually adjust the reflection phase and amplitude and because only one block is involved in performing the spatial FT. Our work may offer a practical, efficient, and flexible approach to the design of compact devices for acoustic computing applications, signal processing, equation solving, and acoustic wave manipulations.

Elimination of autofluorescence background from fluorescence tissue images by use of time-gated detection and the AzaDiOxaTriAngulenium (ADOTA) fluorophore

PubMed Central

Rich, Ryan M.; Stankowska, Dorota L.; Maliwal, Badri P.; Sørensen, Thomas Just; Laursen, Bo W.; Krishnamoorthy, Raghu R.; Gryczynski, Zygmunt; Borejdo, Julian

2013-01-01

Sample autofluorescence (fluorescence of inherent components of tissue and fixative-induced fluorescence) is a significant problem in direct imaging of molecular processes in biological samples. A large variety of naturally occurring fluorescent components in tissue results in broad emission that overlaps the emission of typical fluorescent dyes used for tissue labeling. In addition, autofluorescence is characterized by complex fluorescence intensity decay composed of multiple components whose lifetimes range from sub-nanoseconds to a few nanoseconds. For these reasons, the real fluorescence signal of the probe is difficult to separate from the unwanted autofluorescence. Here we present a method for reducing the autofluorescence problem by utilizing an azadioxatriangulenium (ADOTA) dye with a fluorescence lifetime of approximately 15 ns, much longer than those of most of the components of autofluorescence. A probe with such a long lifetime enables us to use time-gated intensity imaging to separate the signal of the targeting dye from the autofluorescence. We have shown experimentally that by discarding photons detected within the first 20 ns of the excitation pulse, the signal-to-background ratio is improved fivefold. This time-gating eliminates over 96 % of autofluorescence. Analysis using a variable time-gate may enable quantitative determination of the bound probe without the contributions from the background. PMID:23254457

The Regulation of Filamentous Growth in Yeast

PubMed Central

Cullen, Paul J.; Sprague, George F.

2012-01-01

Filamentous growth is a nutrient-regulated growth response that occurs in many fungal species. In pathogens, filamentous growth is critical for host–cell attachment, invasion into tissues, and virulence. The budding yeast Saccharomyces cerevisiae undergoes filamentous growth, which provides a genetically tractable system to study the molecular basis of the response. Filamentous growth is regulated by evolutionarily conserved signaling pathways. One of these pathways is a mitogen activated protein kinase (MAPK) pathway. A remarkable feature of the filamentous growth MAPK pathway is that it is composed of factors that also function in other pathways. An intriguing challenge therefore has been to understand how pathways that share components establish and maintain their identity. Other canonical signaling pathways—rat sarcoma/protein kinase A (RAS/PKA), sucrose nonfermentable (SNF), and target of rapamycin (TOR)—also regulate filamentous growth, which raises the question of how signals from multiple pathways become integrated into a coordinated response. Together, these pathways regulate cell differentiation to the filamentous type, which is characterized by changes in cell adhesion, cell polarity, and cell shape. How these changes are accomplished is also discussed. High-throughput genomics approaches have recently uncovered new connections to filamentous growth regulation. These connections suggest that filamentous growth is a more complex and globally regulated behavior than is currently appreciated, which may help to pave the way for future investigations into this eukaryotic cell differentiation behavior. PMID:22219507

Menstrual cycle phase alters women's sexual preferences for composers of more complex music.

PubMed

Charlton, Benjamin D

2014-06-07

Over 140 years ago Charles Darwin first argued that birdsong and human music, having no clear survival benefit, were obvious candidates for sexual selection. Whereas the first contention is now universally accepted, his theory that music is a product of sexual selection through mate choice has largely been neglected. Here, I provide the first, to my knowledge, empirical support for the sexual selection hypothesis of music evolution by showing that women have sexual preferences during peak conception times for men that are able to create more complex music. Two-alternative forced-choice experiments revealed that woman only preferred composers of more complex music as short-term sexual partners when conception risk was highest. No preferences were displayed when women chose which composer they would prefer as a long-term partner in a committed relationship, and control experiments failed to reveal an effect of conception risk on women's preferences for visual artists. These results suggest that women may acquire genetic benefits for offspring by selecting musicians able to create more complex music as sexual partners, and provide compelling support for Darwin's assertion 'that musical notes and rhythm were first acquired by the male or female progenitors of mankind for the sake of charming the opposite sex'.

A map of brain neuropils and fiber systems in the ant Cardiocondyla obscurior.

PubMed

Bressan, Joris M A; Benz, Martin; Oettler, Jan; Heinze, Jürgen; Hartenstein, Volker; Sprecher, Simon G

2014-01-01

A wide spectrum of occupied ecological niches and spectacular morphological adaptations make social insects a prime object for comparative neuroanatomical studies. Eusocial insects have evolved complex societies based on caste polyphenism. A diverse behavioral repertoire of morphologically distinct castes of the same species requires a high degree of plasticity in the central nervous system. We have analyzed the central brain neuropils and fiber tract systems of the worker of the ant Cardiocondyla obscurior, a model for the study of social traits. Our analysis is based on whole mount preparations of adult brains labeled with an antibody against Drosophila-Synapsin, which cross-reacts strongly with synapses in Cardiocondyla. Neuropil compartments stand out as domains with a certain texture and intensity of the anti-Synapsin signal. By contrast, fiber tracts, which are composed of bundles of axons accompanied by glia and are devoid of synapses, appear as channels or sheaths with low anti-Synapsin signal. We have generated a digital 3D atlas of the Cardiocondyla brain neuropil. The atlas provides a reference for future studies of brain polymorphisms in distinct castes, brain development or localization of neurotransmitter systems.

Intracellular pathways and nuclear localization signal peptide-mediated gene transfection by cationic polymeric nanovectors.

PubMed

Hu, Qinglian; Wang, Jinlei; Shen, Jie; Liu, Min; Jin, Xue; Tang, Guping; Chu, Paul K

2012-02-01

Polyethylenimine (PEI) - based polymers are promising cationic nanovectors. A good understanding of the mechanism by which cationic polymers/DNA complexes are internalized and delivered to nuclei helps to identify which transport steps may be manipulated in order to improve the transfection efficiency. In this work, cell internalization and trafficking of PEI-CyD (PC) composed of β-cyclodextrin (β-CyD) and polyethylenimine (PEI, Mw 600) are studied. The results show that the PC transfected DNA is internalized by binding membrane-associated proteoglycans. The endocytic pathway of the PC particles is caveolae- and clathrin-dependent with both pathways converging to the lysosome. The intracellular fate of the PC provides visual evidence that it can escape from the lysosome. Lysosomal inhibition with chloroquine has no effect on PC mediated transfection implying that blocking the lysosomal traffic does not improve transfection. To improve the nuclear delivery of PC transfected DNA, nuclear localization signal (NLS) peptides are chosen to conjugate and combine with the PC. Compared to PC/pDNA, PC-NLS/pDNA, and PC/pDNA/NLS can effectively improve gene transfection in dividing and non-dividing cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

Functional metabolomics as a tool to analyze Mediator function and structure in plants.

PubMed

Davoine, Celine; Abreu, Ilka N; Khajeh, Khalil; Blomberg, Jeanette; Kidd, Brendan N; Kazan, Kemal; Schenk, Peer M; Gerber, Lorenz; Nilsson, Ove; Moritz, Thomas; Björklund, Stefan

2017-01-01

Mediator is a multiprotein transcriptional co-regulator complex composed of four modules; Head, Middle, Tail, and Kinase. It conveys signals from promoter-bound transcriptional regulators to RNA polymerase II and thus plays an essential role in eukaryotic gene regulation. We describe subunit localization and activities of Mediator in Arabidopsis through metabolome and transcriptome analyses from a set of Mediator mutants. Functional metabolomic analysis based on the metabolite profiles of Mediator mutants using multivariate statistical analysis and heat-map visualization shows that different subunit mutants display distinct metabolite profiles, which cluster according to the reported localization of the corresponding subunits in yeast. Based on these results, we suggest localization of previously unassigned plant Mediator subunits to specific modules. We also describe novel roles for individual subunits in development, and demonstrate changes in gene expression patterns and specific metabolite levels in med18 and med25, which can explain their phenotypes. We find that med18 displays levels of phytoalexins normally found in wild type plants only after exposure to pathogens. Our results indicate that different Mediator subunits are involved in specific signaling pathways that control developmental processes and tolerance to pathogen infections.

Fueling the Flames: Mammalian Programmed Necrosis in Inflammatory Diseases

PubMed Central

Chan, Francis Ka-Ming

2012-01-01

Programmed necrosis or necroptosis is an inflammatory form of cell death driven by TNF-like death cytokines, toll-like receptors, and antigen receptors. Unlike necrosis induced by physical trauma, a dedicated pathway is involved in programmed necrosis. In particular, a kinase complex composed of the receptor interacting protein kinase 1 (RIPK1) and RIPK3 is a central step in necrotic cell death. Assembly and activation of this RIPK1–RIPK3 “necrosome” is critically controlled by protein ubiquitination, phosphorylation, and caspase-mediated cleavage events. The molecular signals cumulate in formation of intracellular vacuoles, organelle swelling, internal membrane leakage, and eventually plasma membrane rupture. These morphological changes can result in spillage of intracellular adjuvants to promote inflammation and further exacerbate tissue injury. Because of the inflammatory nature of necrosis, it is an attractive pathway for therapeutic intervention in acute inflammatory diseases. PMID:23125016

Cancer metabolism in space and time: Beyond the Warburg effect.

PubMed

Danhier, Pierre; Bański, Piotr; Payen, Valéry L; Grasso, Debora; Ippolito, Luigi; Sonveaux, Pierre; Porporato, Paolo E

2017-08-01

Altered metabolism in cancer cells is pivotal for tumor growth, most notably by providing energy, reducing equivalents and building blocks while several metabolites exert a signaling function promoting tumor growth and progression. A cancer tissue cannot be simply reduced to a bulk of proliferating cells. Tumors are indeed complex and dynamic structures where single cells can heterogeneously perform various biological activities with different metabolic requirements. Because tumors are composed of different types of cells with metabolic activities affected by different spatial and temporal contexts, it is important to address metabolism taking into account cellular and biological heterogeneity. In this review, we describe this heterogeneity also in metabolic fluxes, thus showing the relative contribution of different metabolic activities to tumor progression according to the cellular context. This article is part of a Special Issue entitled Mitochondria in Cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux. Copyright © 2017 Elsevier B.V. All rights reserved.

A new, morphologically cryptic bush-cricket discovered on the basis of its song in the Carpathian Mountains (Insecta, Orthoptera, Tettigoniidae).

PubMed

Iorgu, Ionuţ Ştefan; Iorgu, Elena Iulia; Szövényi, Gergely; Orci, Kirill Márk

2017-01-01

A new, morphologically cryptic species of phaneropterine bush-crickets is described from the grasslands of the Romanian Eastern Carpathians. Despite the morphological and acoustic similarities with the recently described Isophya nagyi Szövényi, Puskás & Orci, I. bucovinensis sp. n. is characterized by a peculiar male calling song, with faster syllable repetition rate (160-220 syllables per minute, at 22-27°C) and less complex syllable structure (composed of only two elements instead of three observable in I. nagyi ). The morphological description of the new species is supplemented with an oscillographic and spectrographic analysis of the male calling song and male-female pair-forming acoustic duet. An acoustic signal-based identification key is provided for all the presently known species of the Isophya camptoxypha species group, including the new species.

A new, morphologically cryptic bush-cricket discovered on the basis of its song in the Carpathian Mountains (Insecta, Orthoptera, Tettigoniidae)

PubMed Central

Iorgu, Ionuţ Ştefan; Iorgu, Elena Iulia; Szövényi, Gergely; Orci, Kirill Márk

2017-01-01

Abstract A new, morphologically cryptic species of phaneropterine bush-crickets is described from the grasslands of the Romanian Eastern Carpathians. Despite the morphological and acoustic similarities with the recently described Isophya nagyi Szövényi, Puskás & Orci, I. bucovinensis sp. n. is characterized by a peculiar male calling song, with faster syllable repetition rate (160–220 syllables per minute, at 22–27°C) and less complex syllable structure (composed of only two elements instead of three observable in I. nagyi). The morphological description of the new species is supplemented with an oscillographic and spectrographic analysis of the male calling song and male–female pair-forming acoustic duet. An acoustic signal-based identification key is provided for all the presently known species of the Isophya camptoxypha species group, including the new species. PMID:28769716

New insights on molecular regulation of biofilm formation in plant-associated bacteria.

PubMed

Castiblanco, Luisa F; Sundin, George W

2016-04-01

Biofilms are complex bacterial assemblages with a defined three-dimensional architecture, attached to solid surfaces, and surrounded by a self-produced matrix generally composed of exopolysaccharides, proteins, lipids and extracellular DNA. Biofilm formation has evolved as an adaptive strategy of bacteria to cope with harsh environmental conditions as well as to establish antagonistic or beneficial interactions with their host. Plant-associated bacteria attach and form biofilms on different tissues including leaves, stems, vasculature, seeds and roots. In this review, we examine the formation of biofilms from the plant-associated bacterial perspective and detail the recently-described mechanisms of genetic regulation used by these organisms to orchestrate biofilm formation on plant surfaces. In addition, we describe plant host signals that bacterial pathogens recognize to activate the transition from a planktonic lifestyle to multicellular behavior. © 2015 Institute of Botany, Chinese Academy of Sciences.

Analyte-Triggered DNA-Probe Release from a Triplex Molecular Beacon for Nanopore Sensing.

PubMed

Guo, Bingyuan; Sheng, Yingying; Zhou, Ke; Liu, Quansheng; Liu, Lei; Wu, Hai-Chen

2018-03-26

A new nanopore sensing strategy based on triplex molecular beacon was developed for the detection of specific DNA or multivalent proteins. The sensor is composed of a triplex-forming molecular beacon and a stem-forming DNA component that is modified with a host-guest complex. Upon target DNA hybridizing with the molecular beacon loop or multivalent proteins binding to the recognition elements on the stem, the DNA probe is released and produces highly characteristic current signals when translocated through α-hemolysin. The frequency of current signatures can be used to quantify the concentrations of the target molecules. This sensing approach provides a simple, quick, and modular tool for the detection of specific macromolecules with high sensitivity and excellent selectivity. It may find useful applications in point-of-care diagnostics with a portable nanopore kit in the future. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A novel ultrasonic phased array inspection system to NDT for offshore platform structures

NASA Astrophysics Data System (ADS)

Wang, Hua; Shan, Baohua; Wang, Xin; Ou, Jinping

2007-01-01

A novel ultrasonic phased array detection system is developed for nondestructive testing (NDT). The purpose of the system is to make acquisition of data in real-time from 64-element ultrasonic phased array transducer, and to enable real- time processing of the acquired data. The system is composed of five main parts: master unit, main board, eight transmit/receive units, a 64-element transducer and an external PC. The system can be used with 64 element transducers, excite 32 elements, receive and sample echo signals form 32 elements simultaneously at 62.5MHz with 8 bit precision. The external PC is used as the user interface showing the real time images and controls overall operation of the system through USB serial link. The use of Universal Serial Bus (USB) improves the transform speed and reduces hardware interface complexity. The program of the system is written in Visual C++.NET and is platform independent.

Mechanistic understanding of nanoparticles' interactions with extracellular matrix: the cell and immune system.

PubMed

Engin, Ayse Basak; Nikitovic, Dragana; Neagu, Monica; Henrich-Noack, Petra; Docea, Anca Oana; Shtilman, Mikhail I; Golokhvast, Kirill; Tsatsakis, Aristidis M

2017-06-24

Extracellular matrix (ECM) is an extraordinarily complex and unique meshwork composed of structural proteins and glycosaminoglycans. The ECM provides essential physical scaffolding for the cellular constituents, as well as contributes to crucial biochemical signaling. Importantly, ECM is an indispensable part of all biological barriers and substantially modulates the interchange of the nanotechnology products through these barriers. The interactions of the ECM with nanoparticles (NPs) depend on the morphological characteristics of intercellular matrix and on the physical characteristics of the NPs and may be either deleterious or beneficial. Importantly, an altered expression of ECM molecules ultimately affects all biological processes including inflammation. This review critically discusses the specific behavior of NPs that are within the ECM domain, and passing through the biological barriers. Furthermore, regenerative and toxicological aspects of nanomaterials are debated in terms of the immune cells-NPs interactions.

Why do primordial germ cells migrate through an embryo and what does it mean for biological evolution?

PubMed

Olovnikov, A M

2013-10-01

An explanation of the role of primordial germ cell (PGC) migration during embryogenesis is proposed. According to the hypothesis, various PGCs during their migrations through an early embryo are contacting with anlagen of organs and acquiring nonidentical organ specificities. An individual PGC gets such an organ specificity, which corresponds to specificity of the first anlage with which this PGC has the first contact. As a result, the cellular descendants of PGCs (oocytes or spermatocytes) will express nonidentical organ-specific receptors, hence becoming functionally heterogeneous. Therefore, each clone of germ cells becomes capable of recognizing specifically the molecular signals that correspond only to "its" organ of the body. Such signals are produced by the body's organ when it functions in an extreme mode. Signals from the "exercising" organ of the body are delivered to the gonad only via the brain retransmitter, which is composed of neurons grouped as virtual organs of a homunculus. Homunculi are so-called somatotopic maps of the skeletomotor and other parts of the body represented in the brain. Signals, as complexes of regulatory RNAs and proteins, are transported from the "exercising" organ of the body to the corresponding virtual organ of the homunculus where they are processed and then forwarded to the gonad. The organ-specific signal will be selectively recognized by certain gametocytes according to their organ specificity, and then it will initiate the directed epimutation in the gametocyte genome. The nonrandomness of the gene order in chromosomes, that is the synteny and genetic map, is controlled by the so-called creatron that consolidates the soma and germline into a united system, providing the possibility of evolutionary responses of an organism to environmental influences.

Hologram-reconstruction signal enhancement

NASA Technical Reports Server (NTRS)

Mezrich, R. S.

1977-01-01

Principle of heterodyne detection is used to combine object beam and reconstructed virtual image beam. All light valves in page composer are opened, and virtual-image beam is allowed to interfere with light from valves.

Evidence for the Existence of One Antenna-Associated, Lipid-Dissolved and Two Protein-Bound Pools of Diadinoxanthin Cycle Pigments in Diatoms[C][W

PubMed Central

Lepetit, Bernard; Volke, Daniela; Gilbert, Matthias; Wilhelm, Christian; Goss, Reimund

2010-01-01

We studied the localization of diadinoxanthin cycle pigments in the diatoms Cyclotella meneghiniana and Phaeodactylum tricornutum. Isolation of pigment protein complexes revealed that the majority of high-light-synthesized diadinoxanthin and diatoxanthin is associated with the fucoxanthin chlorophyll protein (FCP) complexes. The characterization of intact cells, thylakoid membranes, and pigment protein complexes by absorption and low-temperature fluorescence spectroscopy showed that the FCPs contain certain amounts of protein-bound diadinoxanthin cycle pigments, which are not significantly different in high-light and low-light cultures. The largest part of high-light-formed diadinoxanthin cycle pigments, however, is not bound to antenna apoproteins but located in a lipid shield around the FCPs, which is copurified with the complexes. This lipid shield is primarily composed of the thylakoid membrane lipid monogalactosyldiacylglycerol. We also show that the photosystem I (PSI) fraction contains a tightly connected FCP complex that is enriched in protein-bound diadinoxanthin cycle pigments. The peripheral FCP and the FCP associated with PSI are composed of different apoproteins. Tandem mass spectrometry analysis revealed that the peripheral FCP is composed mainly of the light-harvesting complex protein Lhcf and also significant amounts of Lhcr. The PSI fraction, on the other hand, shows an enrichment of Lhcr proteins, which are thus responsible for the diadinoxanthin cycle pigment binding. The existence of lipid-dissolved and protein-bound diadinoxanthin cycle pigments in the peripheral antenna and in PSI is discussed with respect to different specific functions of the xanthophylls. PMID:20935178

Development of A Cell-Based Assay to Identify Small Molecule Inhibitors of FGF23 Signaling.

PubMed

Diener, Susanne; Schorpp, Kenji; Strom, Tim-Matthias; Hadian, Kamyar; Lorenz-Depiereux, Bettina

2015-10-01

Fibroblast growth factor 23 (FGF23) is a bone-derived endocrine key regulator of phosphate homeostasis. It inhibits renal tubular phosphate reabsorption by activating receptor complexes composed of FGF receptor 1c (FGFR1c) and the co-receptor Klotho. As a major signaling pathway mitogen-activated protein kinase (MAPK) pathway is employed. In this study, we established an FGF23-inducible cell model by stably expressing human Klotho in HEK293 cells (HEK293-KL cells) containing endogenous FGF receptors. To identify novel small molecule compounds that modulate FGF23/FGFR1c/Klotho signaling, we developed and optimized a cell-based assay that is suited for high-throughput screening. The assay monitors the phosphorylation of endogenous extracellular signal-regulated kinase 1 and 2 in cellular lysates of HEK293-KL cells after induction with FGF23. This cell-based assay was highly robust (Z' factor >0.5) and the induction of the system is strictly dependent on the presence of FGF23. The inhibitor response curves generated using two known MAPK pathway inhibitors correlate well with data obtained by another assay format. This assay was further used to identify small molecule modulators of the FGF23 signaling cascade by screening the 1,280 food and drug administration-approved small molecule library of Prestwick Chemical. The primary hit rate was 2% and false positives were efficiently identified by retesting the hits in primary and secondary validation screening assays and in western blot analysis. Intriguingly, by using a basic FGF (bFGF)/FGFR counterscreening approach, one validated hit compound retained specificity toward FGF23 signaling, while bFGF signaling was not affected. Since increased plasma concentrations of FGF23 are the main cause of many hypophosphatemic disorders, a modulation of its effect could be a potential novel strategy for therapeutic intervention. Moreover, this strategy may be valuable for other disorders affecting phosphate homeostasis.

Amylose-dicarboxylic acid inclusion complexes: Characterization and comparison to monocarboxylic acid complexes

USDA-ARS?s Scientific Manuscript database

One of the main components in starch, amylose is an essentially linear polymer composed of glucose connected through alpha-1,4-bonds. Amylose is well known to form helical inclusion complexes with various types of ligands such as iodine, medium and long chain fatty acids, alcohols, lactones, and fl...

Learning for VMM + WTA Embedded Classifiers

DTIC Science & Technology

2016-03-31

enabling correct classification of each novel acoustic signal (generator, idle car , and idle truck). The classification structure requires, after...measured on our SoC FPAA IC. The test input is composed of signals from urban environment for 3 objects (generator, idle car , and idle truck...classifier results from a rural truck data set, an urban generator set, and urban idle car dataset. Solid lines represent our extracted background

The design of a device for hearer and feeler differentiation, part A. [speech modulated hearing device

NASA Technical Reports Server (NTRS)

Creecy, R.

1974-01-01

A speech modulated white noise device is reported that gives the rhythmic characteristics of a speech signal for intelligible reception by deaf persons. The signal is composed of random amplitudes and frequencies as modulated by the speech envelope characteristics of rhythm and stress. Time intensity parameters of speech are conveyed through the vibro-tactile sensation stimuli.

Empirical transfer functions for stations in the Central California seismological network

USGS Publications Warehouse

Bakun, W.H.; Dratler, Jay

1976-01-01

A sequence of calibration signals composed of a station identification code, a transient from the release of the seismometer mass at rest from a known displacement from the equilibrium position, and a transient from a known step in voltage to the amplifier input are generated by the automatic daily calibration system (ADCS) now operational in the U.S. Geological Survey central California seismographic network. Documentation of a sequence of interactive programs to compute, from the calibration data, the complex transfer functions for the seismographic system (ground motion through digitizer) the electronics (amplifier through digitizer), and the seismometer alone are presented. The analysis utilizes the Fourier transform technique originally suggested by Espinosa et al (1962). Section I is a general description of seismographic calibration. Section II contrasts the 'Fourier transform' and the 'least-squares' techniques for analyzing transient calibration signals. Theoretical consideration for the Fourier transform technique used here are described in Section III. Section IV is a detailed description of the sequence of calibration signals generated by the ADCS. Section V is a brief 'cookbook description' of the calibration programs; Section VI contains a detailed sample program execution. Section VII suggests the uses of the resultant empirical transfer functions. Supplemental interactive programs by which smooth response functions, suitable for reducing seismic data to ground motion, are also documented in Section VII. Appendices A and B contain complete listings of the Fortran source Codes while Appendix C is an update containing preliminary results obtained from an analysis of some of the calibration signals from stations in the seismographic network near Oroville, California.

Uranium deposits in Grant County, New Mexico

USGS Publications Warehouse

Granger, Harry C.; Bauer, Herman L.; Lovering, Tom G.; Gillerman, Elliot

1952-01-01

The known uranium deposits of Grant county, N. Mex., are principally in the White Signal and Black Hawk districts. Both districts are within a northwesterly-trending belt of pre-Cambrian rocks, composed chiefly of granite with included gneisses, schists, and quartzites. Younger dikes and stocks intrude the pre-Cambrian complex. The White Signal district is on the southeast flanks of the Burro Mountains; the Black Hawk district is about 18 miles northwest of the town of White Signal. In the White Signal district the seconday uranium phosphates--autunite and torbernite--occur as fracture coatings and disseminations in oxidized parts of quartz-pyrite veins, and in the adjacent mafic dikes and granites; uraniferous limonite is common locally. Most of the known uraniferous deposits are less that 50 feet in their greatest dimension. The most promising deposits in the district are on the Merry Widow and Blue Jay claims. The richest sample taken from the Merry Widow mine contained more than 2 percent uranium and a sample from the Blue Jay property contained as much as 0.11 percent; samples from the other properties were of lower grade. In the Black Hawk district pitchblende is associated with nickel, silver, and cobalt minerals in fissure veins. The most promising properties in the Black Hawk district are the Black Hawk, Alhambra, and Rose mines. No uranium analyses from this district were available in 1951. There are no known minable reserves of uranium ore in either district, although there is some vein material at the Merry Widow mine of ore grade, if a market were available in the region.

ITO/gold nanoparticle/RGD peptide composites to enhance electrochemical signals and proliferation of human neural stem cells.

PubMed

Kim, Tae-Hyung; El-Said, Waleed Ahmed; An, Jeung Hee; Choi, Jeong-Woo

2013-04-01

A cell chip composed of ITO, gold nanoparticles (GNP) and RGD-MAP-C peptide composites was fabricated to enhance the electrochemical signals and proliferation of undifferentiated human neural stem cells (HB1.F3). The structural characteristics of the fabricated surfaces were confirmed by both scanning electron microscopy and surface-enhanced Raman spectroscopy. HB1.F3 cells were allowed to attach to various composites electrodes in the cell chip and the material-dependent effects on electrochemical signals and cell proliferation were analyzed. The ITO/60 nm GNP/RGD-MAP-C composite electrode was found to be the best material in regards to enhancing the voltammetric signals of HB1.F3 cells when exposed to cyclic voltammetry, as well as for increasing cell proliferation. Differential pulse voltammetry was performed to evaluate the adverse effects of doxorubicin on HB1.F3 cells. In these experiments, negative correlations between cell viability and chemical concentrations were obseved, which were more sensitive than MTT viability assay especially at low concentrations (<0.1 μg/mL). In this basic science study, a cell chip composed of ITO, gold nanoparticles and RGD-MAP-C peptide composites was fabricated to enhance electrochemical signals and proliferation of undifferentiated human neural stem cells (HB1.F3). The ITO/60 nm GNP/RGD-MAP-C composite electrode was found to best enhance the voltammetric signals of the studied cells. Copyright © 2013 Elsevier Inc. All rights reserved.

Two different groups of signal sequence in M-superfamily conotoxins.

PubMed

Wang, Qi; Jiang, Hui; Han, Yu-Hong; Yuan, Duo-Duo; Chi, Cheng-Wu

2008-04-01

M-superfamily conotoxins can be divided into four branches (M-1, M-2, M-3 and M-4) according to the number of amino acid residues in the third Cys loop. In general, it is widely accepted that the conotoxin signal peptides of each superfamily are strictly conserved. Recently, we cloned six cDNAs of novel M-superfamily conotoxins from Conus leopardus, Conus marmoreus and Conus quercinus, belonging to either M-1 or M-3 branch. These conotoxins, judging from the putative peptide sequences deducted from cDNAs, are rich in acidic residues and share highly conserved signal and pro-peptide region. However, they are quite different from the reported conotoxins of M-2 and M-4 branches even in their signal peptides, which in general are considered highly conserved for each superfamily of conotoxins. The signal sequences of M-1 and M-3 conotoxins composed of 24 residues start with MLKMGVVL-, while those of M-2 and M-4 conotoxins composed of 25 residues start with MMSKLGVL-. It is another example that different types of signal peptides can exist within a superfamily besides the I-conotoxin superfamily. In addition to the different disulfide connectivity of M-1 conotoxins from that of M-4 or M-2 conotoxins, the sequence alignment, preferential Cys codon usage and phylogenetic tree analysis suggest that M-1 and M-3 conotoxins have much closer relationship, being different from the conotoxins of other two branches (M-4 and M-2) of M-superfamily.

The fatigue evaluation method for a structural stainless steel using the magnetic sensor composed of three pancake coils

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oka, M.; Tsuchida, Y.; Enokizono, M.

May metallic structural materials, such as stainless steels, are currently used in our surroundings. If external force is repeatedly added for many years, it is thought that fatigue damage accumulates in stainless steels. When excessive fatigue damage accumulates in these metals, there is a possibility that they are destroyed by fatigue damage accumulation. Therefore, it is important to know the amount of the fatigue damage they have suffered in order to prevent them from being destroyed. We are developing the fatigue evaluation method for stainless steels with a magnetic sensor composed of three pancake type coils. In this research, themore » inspection object is ferritic stainless steels such as SUS430. The method of fatigue evaluation for ferritic stainless steels uses the three coil type sensor, and shows a good correlation between the number of stress cycles and the output signal of the sensor, even though the correlation between the output signal and an added stress is not completely accurate. This paper describes the evaluation method of fatigue damage in ferritic stainless steel using a magnetic sensor composed of three pancake-type coils.« less

Residential Interior Design as Complex Composition: A Case Study of a High School Senior's Composing Process

ERIC Educational Resources Information Center

Smagorinsky, Peter; Zoss, Michelle; Reed, Patty M.

2006-01-01

This research analyzed the composing processes of one high school student as she designed the interiors of homes for a course in interior design. Data included field notes, an interview with the teacher, artifacts from the class, and the focal student's concurrent and retrospective protocols in relation to her design of home interiors. The…

Is complex signal processing for bone conduction hearing aids useful?

PubMed

Kompis, Martin; Kurz, Anja; Pfiffner, Flurin; Senn, Pascal; Arnold, Andreas; Caversaccio, Marco

2014-05-01

To establish whether complex signal processing is beneficial for users of bone anchored hearing aids. Review and analysis of two studies from our own group, each comparing a speech processor with basic digital signal processing (either Baha Divino or Baha Intenso) and a processor with complex digital signal processing (either Baha BP100 or Baha BP110 power). The main differences between basic and complex signal processing are the number of audiologist accessible frequency channels and the availability and complexity of the directional multi-microphone noise reduction and loudness compression systems. Both studies show a small, statistically non-significant improvement of speech understanding in quiet with the complex digital signal processing. The average improvement for speech in noise is +0.9 dB, if speech and noise are emitted both from the front of the listener. If noise is emitted from the rear and speech from the front of the listener, the advantage of the devices with complex digital signal processing as opposed to those with basic signal processing increases, on average, to +3.2 dB (range +2.3 … +5.1 dB, p ≤ 0.0032). Complex digital signal processing does indeed improve speech understanding, especially in noise coming from the rear. This finding has been supported by another study, which has been published recently by a different research group. When compared to basic digital signal processing, complex digital signal processing can increase speech understanding of users of bone anchored hearing aids. The benefit is most significant for speech understanding in noise.

Workflow Design Using Fragment Composition

NASA Astrophysics Data System (ADS)

Mosser, Sébastien; Blay-Fornarino, Mireille; France, Robert

The Service-Oriented Architecture (Soa) paradigm supports the assembly of atomic services to create applications that implement complex business processes. Assembly can be accomplished by service orchestrations defined by Soa architects. The Adore method allows Soa architects to model complex orchestrations of services by composing models of smaller orchestrations called orchestration fragments. The Adore method can also be used to weave fragments that address new concerns into existing application models. In this paper we illustrate how the Adore method can be used to separate and compose process aspects in a Soa design of the Car Crash Crisis Management System. The paper also includes a discussion of the benefits and limitations of the Adore method.

DOE Office of Scientific and Technical Information (OSTI.GOV)

AhYoung, Andrew P.; Lu, Brian; Cascio, Duilio

Membrane contact sites between organelles serve as molecular hubs for the exchange of metabolites and signals. In yeast, the Endoplasmic Reticulum – Mitochondrion Encounter Structure (ERMES) tethers these two organelles likely to facilitate the non-vesicular exchange of essential phospholipids. Present in Fungi and Amoebas but not in Metazoans, ERMES is composed of five distinct subunits; among those, Mdm12, Mmm1 and Mdm34 each contain an SMP domain functioning as a lipid transfer module. We previously showed that the SMP domains of Mdm12 and Mmm1 form a hetero-tetramer. Here we describe our strategy to diversify the number of Mdm12/Mmm1 complexes suited formore » structural studies. We use sequence analysis of orthologues combined to protein engineering of disordered regions to guide the design of protein constructs and expand the repertoire of Mdm12/Mmm1 complexes more likely to crystallize. Using this combinatorial approach we report crystals of Mdm12/Mmm1 ERMES complexes currently diffracting to 4.5 Å resolution and a new structure of Mdm12 solved at 4.1 Å resolution. Our structure reveals a monomeric form of Mdm12 with a conformationally dynamic N-terminal β-strand; it differs from a previously reported homodimeric structure where the N-terminal β strands where swapped to promote dimerization. Based on our electron microscopy data, we propose a refined pseudo-atomic model of the Mdm12/Mmm1 complex that agrees with our crystallographic and small-angle X-ray scattering (SAXS) solution data.« less

Element analysis: a wavelet-based method for analysing time-localized events in noisy time series.

PubMed

Lilly, Jonathan M

2017-04-01

A method is derived for the quantitative analysis of signals that are composed of superpositions of isolated, time-localized 'events'. Here, these events are taken to be well represented as rescaled and phase-rotated versions of generalized Morse wavelets, a broad family of continuous analytic functions. Analysing a signal composed of replicates of such a function using another Morse wavelet allows one to directly estimate the properties of events from the values of the wavelet transform at its own maxima. The distribution of events in general power-law noise is determined in order to establish significance based on an expected false detection rate. Finally, an expression for an event's 'region of influence' within the wavelet transform permits the formation of a criterion for rejecting spurious maxima due to numerical artefacts or other unsuitable events. Signals can then be reconstructed based on a small number of isolated points on the time/scale plane. This method, termed element analysis , is applied to the identification of long-lived eddy structures in ocean currents as observed by along-track measurements of sea surface elevation from satellite altimetry.

Novel measurement method of heat and light detection for neutrinoless double beta decay

NASA Astrophysics Data System (ADS)

Kim, G. B.; Choi, J. H.; Jo, H. S.; Kang, C. S.; Kim, H. L.; Kim, I.; Kim, S. R.; Kim, Y. H.; Lee, C.; Lee, H. J.; Lee, M. K.; Li, J.; Oh, S. Y.; So, J. H.

2017-05-01

We developed a cryogenic phonon-scintillation detector to search for 0νββ decay of 100Mo. The detector module, a proto-type setup of the AMoRE experiment, has a scintillating 40Ca100MoO4 absorber composed of 100Mo-enriched and 48Ca-depleted elements. This new detection method employs metallic magnetic calorimeters (MMCs) as the sensor technology for simultaneous detection of heat and light signals. It is designed to have high energy and timing resolutions to increase sensitivity to probe the rare event. The detector, which is composed of a 200 g 40Ca100MoO4 crystal and phonon/photon sensors, showed an energy resolution of 8.7 keV FWHM at 2.6 MeV, with a weak temperature dependence in the range of 10-40 mK. Using rise-time and mean-time parameters and light/heat ratios, the proposed method showed a strong capability of rejecting alpha-induced events from electron events with as good as 20σ separation. Moreover, we discussed how the signal rise-time improves the rejection efficiency for random coincidence signals.

Application of Wave Distribution Function Method to the ERG/PWE Data

NASA Astrophysics Data System (ADS)

Ota, M.; Kasahara, Y.; Matsuda, S.; Kojima, H.; Matsuoka, A.; Hikishima, M.; Kasaba, Y.; Ozaki, M.; Yagitani, S.; Tsuchiya, F.; Kumamoto, A.

2017-12-01

The ERG (Arase) satellite was launched on 20 December 2016 to study acceleration and loss mechanisms of relativistic electrons in the Earth's magnetosphere. The Plasma Wave Experiment (PWE), which is one of the science instruments on board the ERG satellite, measures electric field and magnetic field. The PWE consists of three sub-systems; EFD (Electric Field Detector), OFA/WFC (Onboard Frequency Analyzer and Waveform Capture), and HFA (High Frequency Analyzer).The OFA/WFC measures electromagnetic field spectra and raw waveforms in the frequency range from few Hz to 20 kHz. The OFA produces three kind of data; OFA-SPEC (power spectrum), OFA-MATRIX (spectral matrix), and OFA-COMPLEX (complex spectrum). The OFA-MATRIX measures ensemble averaged complex cross-spectra of two electric field components, and of three magnetic field components. The OFA-COMPLEX measures instantaneous complex spectra of electric and magnetic fields. These data are produced every 8 seconds in the nominal mode, and it can be used for polarization analysis and wave propagation direction finding.In general, spectral matrix composed by cross-spectra of observed signals is used for direction finding, and many algorithms have been proposed. For example, Means method and SVD method can be applied on the assumption that the spectral matrix is consists of a single plane wave, while wave distribution function (WDF) method is applicable even to the data in which multiple numbers of plane waves are simultaneously included. In this presentation, we introduce the results when the WDF method is applied to the ERG/PWE data.

Synthetic analog computation in living cells.

PubMed

Daniel, Ramiz; Rubens, Jacob R; Sarpeshkar, Rahul; Lu, Timothy K

2013-05-30

A central goal of synthetic biology is to achieve multi-signal integration and processing in living cells for diagnostic, therapeutic and biotechnology applications. Digital logic has been used to build small-scale circuits, but other frameworks may be needed for efficient computation in the resource-limited environments of cells. Here we demonstrate that synthetic analog gene circuits can be engineered to execute sophisticated computational functions in living cells using just three transcription factors. Such synthetic analog gene circuits exploit feedback to implement logarithmically linear sensing, addition, ratiometric and power-law computations. The circuits exhibit Weber's law behaviour as in natural biological systems, operate over a wide dynamic range of up to four orders of magnitude and can be designed to have tunable transfer functions. Our circuits can be composed to implement higher-order functions that are well described by both intricate biochemical models and simple mathematical functions. By exploiting analog building-block functions that are already naturally present in cells, this approach efficiently implements arithmetic operations and complex functions in the logarithmic domain. Such circuits may lead to new applications for synthetic biology and biotechnology that require complex computations with limited parts, need wide-dynamic-range biosensing or would benefit from the fine control of gene expression.

Stereotypy and variability of social calls among clustering female big-footed myotis (Myotis macrodactylus).

PubMed

Xiao, Yan-Hong; Wang, Lei; Hoyt, Joseph R; Jiang, Ting-Lei; Lin, Ai-Qing; Feng, Jiang

2018-03-18

Echolocating bats have developed advanced auditory perception systems, predominantly using acoustic signaling to communicate with each other. They can emit a diverse range of social calls in complex behavioral contexts. This study examined the vocal repertoire of five pregnant big-footed myotis bats (Myotis macrodactylus). In the process of clustering, the last individual to return to the colony (LI) emitted social calls that correlated with behavior, as recorded on a PC-based digital recorder. These last individuals could emit 10 simple monosyllabic and 27 complex multisyllabic types of calls, constituting four types of syllables. The social calls were composed of highly stereotyped syllables, hierarchically organized by a common set of syllables. However, intra-specific variation was also found in the number of syllables, syllable order and patterns of syllable repetition across call renditions. Data were obtained to characterize the significant individual differences that existed in the maximum frequency and duration of calls. Time taken to return to the roost was negatively associated with the diversity of social calls. Our findings indicate that variability in social calls may be an effective strategy taken by individuals during reintegration into clusters of female M. macrodactylus.

The Classical Pathways of Occipital Lobe Epileptic Propagation Revised in the Light of White Matter Dissection

PubMed Central

Latini, Francesco; Hjortberg, Mats; Aldskogius, Håkan; Ryttlefors, Mats

2015-01-01

The clinical evidences of variable epileptic propagation in occipital lobe epilepsy (OLE) have been demonstrated by several studies. However the exact localization of the epileptic focus sometimes represents a problem because of the rapid propagation to frontal, parietal, or temporal regions. Each white matter pathway close to the supposed initial focus can lead the propagation towards a specific direction, explaining the variable semiology of these rare epilepsy syndromes. Some new insights in occipital white matter anatomy are herein described by means of white matter dissection and compared to the classical epileptic patterns, mostly based on the central position of the primary visual cortex. The dissections showed a complex white matter architecture composed by vertical and longitudinal bundles, which are closely interconnected and segregated and are able to support specific high order functions with parallel bidirectional propagation of the electric signal. The same sublobar lesions may hyperactivate different white matter bundles reemphasizing the importance of the ictal semiology as a specific clinical demonstration of the subcortical networks recruited. Merging semiology, white matter anatomy, and electrophysiology may lead us to a better understanding of these complex syndromes and tailored therapeutic options based on individual white matter connectivity. PMID:26063964

Perspectives for the use of structural information and chemical genetics to develop inhibitors of Janus kinases

PubMed Central

Haan, Claude; Behrmann, Iris; Haan, Serge

2010-01-01

Abstract Gain-of-function mutations in the genes encoding Janus kinases have been discovered in various haematologic diseases. Jaks are composed of a FERM domain, an SH2 domain, a pseudokinase domain and a kinase domain, and a complex interplay of the Jak domains is involved in regulation of catalytic activity and association to cytokine receptors. Most activating mutations are found in the pseudokinase domain. Here we present recently discovered mutations in the context of our structural models of the respective domains. We describe two structural hotspots in the pseudokinase domain of Jak2 that seem to be associated either to myeloproliferation or to lymphoblastic leukaemia, pointing at the involvement of distinct signalling complexes in these disease settings. The different domains of Jaks are discussed as potential drug targets. We present currently available inhibitors targeting Jaks and indicate structural differences in the kinase domains of the different Jaks that may be exploited in the development of specific inhibitors. Moreover, we discuss recent chemical genetic approaches which can be applied to Jaks to better understand the role of these kinases in their biological settings and as drug targets. PMID:20132407

A web platform for the network analysis of high-throughput data in melanoma and its use to investigate mechanisms of resistance to anti-PD1 immunotherapy.

PubMed

Dreyer, Florian S; Cantone, Martina; Eberhardt, Martin; Jaitly, Tanushree; Walter, Lisa; Wittmann, Jürgen; Gupta, Shailendra K; Khan, Faiz M; Wolkenhauer, Olaf; Pützer, Brigitte M; Jäck, Hans-Martin; Heinzerling, Lucie; Vera, Julio

2018-06-01

Cellular phenotypes are established and controlled by complex and precisely orchestrated molecular networks. In cancer, mutations and dysregulations of multiple molecular factors perturb the regulation of these networks and lead to malignant transformation. High-throughput technologies are a valuable source of information to establish the complex molecular relationships behind the emergence of malignancy, but full exploitation of this massive amount of data requires bioinformatics tools that rely on network-based analyses. In this report we present the Virtual Melanoma Cell, an online tool developed to facilitate the mining and interpretation of high-throughput data on melanoma by biomedical researches. The platform is based on a comprehensive, manually generated and expert-validated regulatory map composed of signaling pathways important in malignant melanoma. The Virtual Melanoma Cell is a tool designed to accept, visualize and analyze user-generated datasets. It is available at: https://www.vcells.net/melanoma. To illustrate the utilization of the web platform and the regulatory map, we have analyzed a large publicly available dataset accounting for anti-PD1 immunotherapy treatment of malignant melanoma patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Sestrin2 inhibits mTORC1 through modulation of GATOR complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Jeong Sig; Ro, Seung-Hyun; Kim, Myungjin

2015-03-30

Sestrins are stress-inducible metabolic regulators that suppress a wide range of age- and obesity-associated pathologies, many of which are due to mTORC1 overactivation. Upon various stresses, the Sestrins inhibit mTORC1 activity through an indirect mechanism that is still unclear. GATORs are recently identified protein complexes that regulate the activity of RagB, a small GTPase essential for mTORC1 activation. GATOR1 is a GTPase activating protein (GAP) for RagB whereas GATOR2 functions as an inhibitor of GATOR1. However, how the GATORs are physiologically regulated is unknown. Here we show that Sestrin2 binds to GATOR2, and liberates GATOR1 from GATOR2-mediated inhibition. Released GATOR1more » subsequently binds to and inactivates RagB, ultimately resulting in mTORC1 suppression. Consistent with this biochemical mechanism, genetic ablation of GATOR1 nullifies the mTORC1-inhibiting effect of Sestrin2 in both cell culture and Drosophila models. Collectively, we elucidate a new signaling cascade composed of Sestrin2-GATOR2-GATOR1-RagB that mediates stress-dependent suppression of mTORC1 activity.« less

Switches from pi- to sigma-bonding complexes controlled by gate voltages.

PubMed

Matsui, Eriko; Harnack, Oliver; Matsuzawa, Nobuyuki N; Yasuda, Akio

2005-10-01

A conjugated polymer/metal ion/liquid-crystal molecular system was set between source and drain electrodes with a 100 nm gap. When gate voltage (Vg) increases, the current between source and drain electrodes increases. Infrared spectra show this system to be composed of pi and sigma complexes. At Vg = 0, the pi complex dominates the sigma complex, whereas the sigma complex becomes dominant when Vg is switched on. Calculations found that the pi complex has lower conductivity than the sigma complex.

Music and emotion-a composer's perspective.

PubMed

Douek, Joel

2013-01-01

This article takes an experiential and anecdotal look at the daily lives and work of film composers as creators of music. It endeavors to work backwards from what practitioners of the art and craft of music do instinctively or unconsciously, and try to shine a light on it as a conscious process. It examines the role of the film composer in his task to convey an often complex set of emotions, and communicate with an immediacy and universality that often sit outside of common language. Through the experiences of the author, as well as interviews with composer colleagues, this explores both concrete and abstract ways in which music can bring meaning and magic to words and images, and as an underscore to our daily lives.

Music and emotion—a composer's perspective

PubMed Central

Douek, Joel

2013-01-01

This article takes an experiential and anecdotal look at the daily lives and work of film composers as creators of music. It endeavors to work backwards from what practitioners of the art and craft of music do instinctively or unconsciously, and try to shine a light on it as a conscious process. It examines the role of the film composer in his task to convey an often complex set of emotions, and communicate with an immediacy and universality that often sit outside of common language. Through the experiences of the author, as well as interviews with composer colleagues, this explores both concrete and abstract ways in which music can bring meaning and magic to words and images, and as an underscore to our daily lives. PMID:24348344

Functional characterization of Anaphase Promoting Complex/Cyclosome (APC/C) E3 ubiquitin ligases in tumorigenesis

PubMed Central

Zhang, Jinfang; Wan, Lixin; Dai, Xiangpeng; Sun, Yi; Wei, Wenyi

2014-01-01

The Anaphase Promoting Complex/Cyclosome (APC/C) is a multi-subunit E3 ubiquitin ligase that primarily governs cell cycle progression. APC/C is composed of at least 14 core subunits and recruits its substrates for ubiquitination via one of the two adaptor proteins, Cdc20 or Cdh1, in M or M/early G1 phase, respectively. Furthermore, recent studies have shed light on crucial functions for APC/C in maintaining genomic integrity, neuronal differentiation, cellular metabolism and tumorigenesis. To gain better insight into the in vivo physiological functions of APC/C in regulating various cellular processes, particularly development and tumorigenesis, a number of mouse models of APC/C core subunits, coactivators or inhibitors have been established and characterized. However, due to their essential role in cell cycle regulation, most of the germline knockout mice targeting the APC/C pathway are embryonic lethal, indicating the need for generating conditional knockout mouse models to assess the role in tumorigenesis for each APC/C signaling component in specific tissues. In this review, we will first provide a brief introduction of the ubiquitin-proteasome system (UPS) and the biochemical activities and cellular functions of the APC/C E3 ligase. We will then focus primarily on characterizing genetic mouse models used to understand the physiological roles of each APC/C signaling component in embryogenesis, cell proliferation, development and carcinogenesis. Finally, we discuss future research directions to further elucidate the physiological contributions of APC/C components during tumorigenesis and validate their potentials as a novel class of anti-cancer targets. PMID:24569229

Evolution of an RNP assembly system: A minimal SMN complex facilitates formation of UsnRNPs in Drosophila melanogaster

PubMed Central

Kroiss, Matthias; Schultz, Jörg; Wiesner, Julia; Chari, Ashwin; Sickmann, Albert; Fischer, Utz

2008-01-01

In vertebrates, assembly of spliceosomal uridine-rich small nuclear ribonucleoproteins (UsnRNPs) is mediated by the SMN complex, a macromolecular entity composed of the proteins SMN and Gemins 2–8. Here we have studied the evolution of this machinery using complete genome assemblies of multiple model organisms. The SMN complex has gained complexity in evolution by a blockwise addition of Gemins onto an ancestral core complex composed of SMN and Gemin2. In contrast to this overall evolutionary trend to more complexity in metazoans, orthologs of most Gemins are missing in dipterans. In accordance with these bioinformatic data a previously undescribed biochemical purification strategy elucidated that the dipteran Drosophila melanogaster contains an SMN complex of remarkable simplicity. Surprisingly, this minimal complex not only mediates the assembly reaction in a manner very similar to its vertebrate counterpart, but also prevents misassembly onto nontarget RNAs. Our data suggest that only a minority of Gemins are required for the assembly reaction per se, whereas others may serve additional functions in the context of UsnRNP biogenesis. The evolution of the SMN complex is an interesting example of how the simplification of a biochemical process contributes to genome compaction. PMID:18621711

The sequence measurement system of the IR camera

NASA Astrophysics Data System (ADS)

Geng, Ai-hui; Han, Hong-xia; Zhang, Hai-bo

2011-08-01

Currently, the IR cameras are broadly used in the optic-electronic tracking, optic-electronic measuring, fire control and optic-electronic countermeasure field, but the output sequence of the most presently applied IR cameras in the project is complex and the giving sequence documents from the leave factory are not detailed. Aiming at the requirement that the continuous image transmission and image procession system need the detailed sequence of the IR cameras, the sequence measurement system of the IR camera is designed, and the detailed sequence measurement way of the applied IR camera is carried out. The FPGA programming combined with the SignalTap online observation way has been applied in the sequence measurement system, and the precise sequence of the IR camera's output signal has been achieved, the detailed document of the IR camera has been supplied to the continuous image transmission system, image processing system and etc. The sequence measurement system of the IR camera includes CameraLink input interface part, LVDS input interface part, FPGA part, CameraLink output interface part and etc, thereinto the FPGA part is the key composed part in the sequence measurement system. Both the video signal of the CmaeraLink style and the video signal of LVDS style can be accepted by the sequence measurement system, and because the image processing card and image memory card always use the CameraLink interface as its input interface style, the output signal style of the sequence measurement system has been designed into CameraLink interface. The sequence measurement system does the IR camera's sequence measurement work and meanwhile does the interface transmission work to some cameras. Inside the FPGA of the sequence measurement system, the sequence measurement program, the pixel clock modification, the SignalTap file configuration and the SignalTap online observation has been integrated to realize the precise measurement to the IR camera. Te sequence measurement program written by the verilog language combining the SignalTap tool on line observation can count the line numbers in one frame, pixel numbers in one line and meanwhile account the line offset and row offset of the image. Aiming at the complex sequence of the IR camera's output signal, the sequence measurement system of the IR camera accurately measures the sequence of the project applied camera, supplies the detailed sequence document to the continuous system such as image processing system and image transmission system and gives out the concrete parameters of the fval, lval, pixclk, line offset and row offset. The experiment shows that the sequence measurement system of the IR camera can get the precise sequence measurement result and works stably, laying foundation for the continuous system.

Fish Swim, Rocks Sit, and Lungs Breathe: Expert-Novice Understanding of Complex Systems

ERIC Educational Resources Information Center

Hmelo-Silver, Cindy E.; Marathe, Surabhi; Liu, Lei

2007-01-01

Understanding complex systems is fundamental to understanding science. The complexity of such systems makes them very difficult to understand because they are composed of multiple interrelated levels that interact in dynamic ways. The goal of this study was to understand how experts and novices differed in their understanding of two complex…

Markov Chain Analysis of Musical Dice Games

NASA Astrophysics Data System (ADS)

Volchenkov, D.; Dawin, J. R.

2012-07-01

A system for using dice to compose music randomly is known as the musical dice game. The discrete time MIDI models of 804 pieces of classical music written by 29 composers have been encoded into the transition matrices and studied by Markov chains. Contrary to human languages, entropy dominates over redundancy, in the musical dice games based on the compositions of classical music. The maximum complexity is achieved on the blocks consisting of just a few notes (8 notes, for the musical dice games generated over Bach's compositions). First passage times to notes can be used to resolve tonality and feature a composer.

Musical Markov Chains

NASA Astrophysics Data System (ADS)

Volchenkov, Dima; Dawin, Jean René

A system for using dice to compose music randomly is known as the musical dice game. The discrete time MIDI models of 804 pieces of classical music written by 29 composers have been encoded into the transition matrices and studied by Markov chains. Contrary to human languages, entropy dominates over redundancy, in the musical dice games based on the compositions of classical music. The maximum complexity is achieved on the blocks consisting of just a few notes (8 notes, for the musical dice games generated over Bach's compositions). First passage times to notes can be used to resolve tonality and feature a composer.

Supramolecular assembly of the beta-catenin destruction complex and the effect of Wnt signaling on its localization, molecular size, and activity in vivo

PubMed Central

Schaefer, Kristina N.; Williams, Clara E.; Roberts, David M.; McKay, Daniel J.

2018-01-01

Wnt signaling provides a paradigm for cell-cell signals that regulate embryonic development and stem cell homeostasis and are inappropriately activated in cancers. The tumor suppressors APC and Axin form the core of the multiprotein destruction complex, which targets the Wnt-effector beta-catenin for phosphorylation, ubiquitination and destruction. Based on earlier work, we hypothesize that the destruction complex is a supramolecular entity that self-assembles by Axin and APC polymerization, and that regulating assembly and stability of the destruction complex underlie its function. We tested this hypothesis in Drosophila embryos, a premier model of Wnt signaling. Combining biochemistry, genetic tools to manipulate Axin and APC2 levels, advanced imaging and molecule counting, we defined destruction complex assembly, stoichiometry, and localization in vivo, and its downregulation in response to Wnt signaling. Our findings challenge and revise current models of destruction complex function. Endogenous Axin and APC2 proteins and their antagonist Dishevelled accumulate at roughly similar levels, suggesting competition for binding may be critical. By expressing Axin:GFP at near endogenous levels we found that in the absence of Wnt signals, Axin and APC2 co-assemble into large cytoplasmic complexes containing tens to hundreds of Axin proteins. Wnt signals trigger recruitment of these to the membrane, while cytoplasmic Axin levels increase, suggesting altered assembly/disassembly. Glycogen synthase kinase3 regulates destruction complex recruitment to the membrane and release of Armadillo/beta-catenin from the destruction complex. Manipulating Axin or APC2 levels had no effect on destruction complex activity when Wnt signals were absent, but, surprisingly, had opposite effects on the destruction complex when Wnt signals were present. Elevating Axin made the complex more resistant to inactivation, while elevating APC2 levels enhanced inactivation. Our data suggest both absolute levels and the ratio of these two core components affect destruction complex function, supporting models in which competition among Axin partners determines destruction complex activity. PMID:29641560

Vps26B-retromer negatively regulates plasma membrane resensitization of PAR-2.

PubMed

Bugarcic, Andrea; Vetter, Irina; Chalmers, Silke; Kinna, Genevieve; Collins, Brett M; Teasdale, Rohan D

2015-11-01

Retromer is a trimeric complex composed of Vps26, Vps29, and Vps35 and has been shown to be involved in trafficking and sorting of transmembrane proteins within the endosome. The Vps26 paralog, Vps26B, defines a distinct retromer complex (Vps26B-retromer) in vivo and in vitro. Although endosomally associated, Vps26B-retromer does not bind the established retromer transmembrane cargo protein, cation-independent mannose 6-phosphate receptor (CI-M6PR), indicating it has a distinct role to retromer containing the Vps26A paralog. In the present study we use the previously established Vps26B-expressing HEK293 cell model to address the role of Vps26B-retromer in trafficking of the protease activated G-protein coupled receptor PAR-2 to the plasma membrane. In these cells there is no apparent defect in the initial activation of the receptor, as evidenced by release of intracellular calcium, ERK1/2 signaling and endocytosis of activated receptor PAR-2 into degradative organelles. However, we observe a significant delay in plasma membrane repopulation of the protease activated G protein-coupled receptor PAR-2 following stimulation, resulting in a defect in PAR-2 activation after resensitization. Here we propose that PAR-2 plasma membrane repopulation is regulated by Vps26B-retromer, describing a potential novel role for this complex. © 2015 International Federation for Cell Biology.

Structure of the large FK506-binding protein FKBP51, an Hsp90-binding protein and a component of steroid receptor complexes

PubMed Central

Sinars, Cindy R.; Cheung-Flynn, Joyce; Rimerman, Ronald A.; Scammell, Jonathan G.; Smith, David F.; Clardy, Jon

2003-01-01

The ability to bind immunosuppressive drugs such as cyclosporin and FK506 defines the immunophilin family of proteins, and the FK506-binding proteins form the FKBP subfamily of immunophilins. Some FKBPs, notably FKBP12 (the 12-kDa FK506-binding protein), have defined roles in regulating ion channels or cell signaling, and well established structures. Other FKBPs, especially the larger ones, participate in important biological processes, but their exact roles and the structural bases for these roles are poorly defined. FKBP51 (the 51-kDa FKBP) associates with heat shock protein 90 (Hsp90) and appears in functionally mature steroid receptor complexes. In New World monkeys, FKBP51 has been implicated in cortisol resistance. We report here the x-ray structures of human FKBP51, to 2.7 Å, and squirrel monkey FKBP51, to 2.8 Å, by using multiwavelength anomalous dispersion phasing. FKBP51 is composed of three domains: two consecutive FKBP domains and a three-unit repeat of the TPR (tetratricopeptide repeat) domain. This structure of a multi-FKBP domain protein clarifies the arrangement of these domains and their possible interactions with other proteins. The two FKBP domains differ by an insertion in the second that affects the formation of the progesterone receptor complex. PMID:12538866

Atomic features of an autoantigen in heparin-induced thrombocytopenia (HIT).

PubMed

Cai, Zheng; Zhu, Zhiqiang; Greene, Mark I; Cines, Douglas B

2016-07-01

Autoantigen development is poorly understood at the atomic level. Heparin-induced thrombocytopenia (HIT) is an autoimmune thrombotic disorder caused by antibodies to an antigen composed of platelet factor 4 (PF4) and heparin or cellular glycosaminoglycans (GAGs). In solution, PF4 exists as an equilibrium among monomers, dimers and tetramers. Structural studies of these interacting components helped delineate a multi-step process involved in the pathogenesis of HIT. First, heparin binds to the 'closed' end of the PF4 tetramer and stabilizes its conformation; exposing the 'open' end. Second, PF4 arrays along heparin/GAG chains, which approximate tetramers, form large antigenic complexes that enhance antibody avidity. Third, pathogenic HIT antibodies bind to the 'open' end of stabilized PF4 tetramers to form an IgG/PF4/heparin ternary immune complex and also to propagate the formation of 'ultralarge immune complexes' (ULCs) that contain multiple IgG antibodies. Fourth, ULCs signal through FcγRIIA receptors, activating platelets and monocytes directly and generating thrombin, which transactivates hematopoietic and endothelial cells. A non-pathogenic anti-PF4 antibody prevents tetramer formation, binding of pathogenic antibody, platelet activation and thrombosis, providing a new approach to manage HIT. An improved understanding of the pathogenesis of HIT may lead to novel diagnostics and therapeutics for this autoimmune disease. Copyright © 2016 Elsevier B.V. All rights reserved.

Copper signaling in the brain and beyond.

PubMed

Ackerman, Cheri M; Chang, Christopher J

2018-03-30

Transition metals have been recognized and studied primarily in the context of their essential roles as structural and metabolic cofactors for biomolecules that compose living systems. More recently, an emerging paradigm of transition-metal signaling, where dynamic changes in transitional metal pools can modulate protein function, cell fate, and organism health and disease, has broadened our view of the potential contributions of these essential nutrients in biology. Using copper as a canonical example of transition-metal signaling, we highlight key experiments where direct measurement and/or visualization of dynamic copper pools, in combination with biochemical, physiological, and behavioral studies, have deciphered sources, targets, and physiological effects of copper signals.

Statistical performance evaluation of ECG transmission using wireless networks.

PubMed

Shakhatreh, Walid; Gharaibeh, Khaled; Al-Zaben, Awad

2013-07-01

This paper presents simulation of the transmission of biomedical signals (using ECG signal as an example) over wireless networks. Investigation of the effect of channel impairments including SNR, pathloss exponent, path delay and network impairments such as packet loss probability; on the diagnosability of the received ECG signal are presented. The ECG signal is transmitted through a wireless network system composed of two communication protocols; an 802.15.4- ZigBee protocol and an 802.11b protocol. The performance of the transmission is evaluated using higher order statistics parameters such as kurtosis and Negative Entropy in addition to the common techniques such as the PRD, RMS and Cross Correlation.

Multistate Lempel-Ziv (MLZ) index interpretation as a measure of amplitude and complexity changes.

PubMed

Sarlabous, Leonardo; Torres, Abel; Fiz, Jose A; Gea, Joaquim; Galdiz, Juan B; Jane, Raimon

2009-01-01

The Lempel-Ziv complexity (LZ) has been widely used to evaluate the randomness of finite sequences. In general, the LZ complexity has been used to determine the complexity grade present in biomedical signals. The LZ complexity is not able to discern between signals with different amplitude variations and similar random components. On the other hand, amplitude parameters, as the root mean square (RMS), are not able to discern between signals with similar power distributions and different random components. In this work, we present a novel method to quantify amplitude and complexity variations in biomedical signals by means of the computation of the LZ coefficient using more than two quantification states, and with thresholds fixed and independent of the dynamic range or standard deviation of the analyzed signal: the Multistate Lempel-Ziv (MLZ) index. Our results indicate that MLZ index with few quantification levels only evaluate the complexity changes of the signal, with high number of levels, the amplitude variations, and with an intermediate number of levels informs about both amplitude and complexity variations. The study performed in diaphragmatic mechanomyographic signals shows that the amplitude variations of this signal are more correlated with the respiratory effort than the complexity variations. Furthermore, it has been observed that the MLZ index with high number of levels practically is not affected by the existence of impulsive, sinusoidal, constant and Gaussian noises compared with the RMS amplitude parameter.

Two Years of Simultaneous K(sub a)-Band Measurements: Goldstone, CA; White Sands, NM; and Guam, USA

NASA Technical Reports Server (NTRS)

Acosta, Roberto J.; Zemba, M.; Morse, J.; Nessel, J.

2012-01-01

In order to statistically characterize the effect of the Earth's atmosphere on Ka-Band links, site test interferometers (STIs) have been deployed at three of NASA s operational sites to directly measure each site's tropospheric phase stability and rain attenuation. These STIs are composed of two antennas on a short baseline (less than 1km) that observe the same unmodulated beacon signal broadcast from a geostationary satellite (e.g., Anik F2). The STIs are used to measure the differential phase between the two received signals as well as the individual signal attenuation at each terminal. There are currently three NASA sites utilizing STIs; the Goldstone Deep Space Communications Complex near Barstow, California; the White Sands Complex in Las Cruces, New Mexico; and the Guam Remote Ground Terminal on the island of Guam. The first two sites are both located in desert regions that have highly similar climates in terms of their seasonal temperatures, average humidity, and annual rain fall (the primary factors in determining phase stability). In contrast, Guam is in a tropical region with drastically higher annual rainfall and humidity. Five station years of data have been collected in Goldstone, three in White Sands, and two in Guam, yielding two years of simultaneous data collection across all three sites. During this period of simultaneous data collection, the root-mean-square (RMS) of the time delay fluctuations stayed under 2.40 picoseconds for 90% of the time in Goldstone, under 2.07 picoseconds for 90% of the time in White Sands, and under 10.13 picoseconds for 90% of the time in Guam. For the 99th percentile, the statistics were 6.32 ps, 6.03 ps, and 24.85 ps, respectively. These values, as well as various other site quality characteristics, will be used to determine the suitability of these sites for NASA s future communication services at Ka-Band.

Malaria Parasite CLAG3, a Protein Linked to Nutrient Channels, Participates in High Molecular Weight Membrane-Associated Complexes in the Infected Erythrocyte

PubMed Central

Zainabadi, Kayvan

2016-01-01

Malaria infected erythrocytes show increased permeability to a number of solutes important for parasite growth as mediated by the Plasmodial Surface Anion Channel (PSAC). The P. falciparum clag3 genes have recently been identified as key determinants of PSAC, though exactly how they contribute to channel function and whether additional host/parasite proteins are required remain unknown. To begin to answer these questions, I have taken a biochemical approach. Here I have used an epitope-tagged CLAG3 parasite to perform co-immunoprecipitation experiments using membrane fractions of infected erythrocytes. Native PAGE and mass spectrometry studies reveal that CLAG3 participate in at least three different high molecular weight complexes: a ~720kDa complex consisting of CLAG3, RHOPH2 and RHOPH3; a ~620kDa complex consisting of CLAG3 and RHOPH2; and a ~480kDa complex composed solely of CLAG3. Importantly, these complexes can be found throughout the parasite lifecycle but are absent in untransfected controls. Extracellular biotin labeling and protease susceptibility studies localize the 480kDa complex to the erythrocyte membrane. This complex, likely composed of a homo-oligomer of 160kDa CLAG3, may represent a functional subunit, possibly the pore, of PSAC. PMID:27299521

Two Years of Site Diversity Measurements in Guam, USA

NASA Technical Reports Server (NTRS)

Acosta, Roberto J.; Morse, J.; Zemba, M.; Nessel, J.

2012-01-01

As NASA communication networks upgrade to higher frequencies, such as Ka-Band, atmospherically induced attenuation can become significant. This attenuation is caused by rain, clouds and atmospheric gases (oxygen and water vapor), with rain having the most noticeable effects. One technique to circumvent the increase in attenuation is to operate two terminals separated by a distance that exceeds the average rain cell size. The fact that rain cells are of finite size can then be exploited by rerouting the signal to the terminal with the strongest link. This technique, known as site diversity, is best suited for climates that have compact (less than 2km) and intense rain cells such as in Guam. In order to study the potential diversity gain at the Tracking and Data Relay Satellite (TDRS) Remote Ground Terminal (GRGT) complex in Guam a site test interferometer (STI) was installed in May of 2010. The STI is composed of two terminals with a 900m baseline that observe the same unmodulated beacon signal broadcast from a geostationary satellite (e.g., UFO 8). The potential site diversity gain is calculated by measuring the difference in signal attenuation seen at each terminal. Over the two years of data collection the cumulative distribution function (CDF) of the site diversity gain shows a better than 3 dB improvement for 90% of the time over standard operation. These results show that the use of site diversity in Guam can be very effective in combating rain fades.

Superparamagnetic And Paramagnetic MRI Contrast Agents: Application Of Rapid Magnetic Resonance Imaging To Assess Renal Function

NASA Astrophysics Data System (ADS)

Carvlin, Mark J.; Renshaw, Perry F.; Arger, Peter; Kundel, Harold L.; Dougherty, Larry; Axel, Leon; Kassab, Eleanor; Moore, Bethanne

1988-06-01

The paramagnetic chelate complex, gadolinium-diethylene-triamine-pentaacetic acid, Gd-DTPA, and superparamagnetic particles, such as those composed of dextran coated magnetite, function as magnetic resonance contrast agents by changing the relaxation rates, 1/T1 and 1/T2. The effects that these agents have upon MR signal intensity are determined by: the inherent biophysical properties of the tissue being imaged, the concentration of the contrast agent and the data acquisition scheme (pulse sequence parameters) employed. Following the time course of MR signal change in the first minutes after the injection of contrast agent(s) allows a dynamic assessment of organ functions in a manner analogous to certain nuclear medicine studies. In order to study renal function, sequential MR fast scan images, gradient echo (TR=35/TE=7 msec, flip angle=25 degrees), were acquired, one every 12 seconds, after intravenous injection of Gd-DTPA and/or dextran-magnetite. Gd-DTPA, which is freely filtered at the glomerulus and is neither secreted nor reabsorbed, provides information concerning renal perfusion, glomerular filtration and tubular concentrating ability. Dextran-magnetite (200 A diameter), which is primarily contained within the intravascular space shortly after injection, provides information on blood flow to and distribution within the kidney. The MR signal change observed after administration of contrast agents varied dramatically depending upon the agents injected and the imaging parameters used. Hence a broad range of physiolgic processes may be described using these techniques, i.e. contrast agent enhanced functional MR examinations.

Regulation of T cell receptor complex-mediated signaling by ubiquitin and ubiquitin-like modifications.

PubMed

Friend, Samantha F; Deason-Towne, Francina; Peterson, Lisa K; Berger, Allison J; Dragone, Leonard L

2014-01-01

Post-translational protein modifications are a dynamic method of regulating protein function in response to environmental signals. As with any cellular process, T cell receptor (TCR) complex-mediated signaling is highly regulated, since the strength and duration of TCR-generated signals governs T cell development and activation. While regulation of TCR complex-mediated signaling by phosphorylation has been well studied, regulation by ubiquitin and ubiquitin-like modifiers is still an emerging area of investigation. This review will examine how ubiquitin, E3 ubiquitin ligases, and other ubiquitin-like modifications such as SUMO and NEDD8 regulate TCR complex-mediated signaling.

Regulation of T cell receptor complex-mediated signaling by ubiquitin and ubiquitin-like modifications

PubMed Central

Friend, Samantha F; Deason-Towne, Francina; Peterson, Lisa K; Berger, Allison J; Dragone, Leonard L

2014-01-01

Post-translational protein modifications are a dynamic method of regulating protein function in response to environmental signals. As with any cellular process, T cell receptor (TCR) complex-mediated signaling is highly regulated, since the strength and duration of TCR-generated signals governs T cell development and activation. While regulation of TCR complex-mediated signaling by phosphorylation has been well studied, regulation by ubiquitin and ubiquitin-like modifiers is still an emerging area of investigation. This review will examine how ubiquitin, E3 ubiquitin ligases, and other ubiquitin-like modifications such as SUMO and NEDD8 regulate TCR complex-mediated signaling. PMID:25628960

Stochastic simulations of a synthetic bacteria-yeast ecosystem

PubMed Central

2012-01-01

Background The field of synthetic biology has greatly evolved and numerous functions can now be implemented by artificially engineered cells carrying the appropriate genetic information. However, in order for the cells to robustly perform complex or multiple tasks, co-operation between them may be necessary. Therefore, various synthetic biological systems whose functionality requires cell-cell communication are being designed. These systems, microbial consortia, are composed of engineered cells and exhibit a wide range of behaviors. These include yeast cells whose growth is dependent on one another, or bacteria that kill or rescue each other, synchronize, behave as predator-prey ecosystems or invade cancer cells. Results In this paper, we study a synthetic ecosystem comprising of bacteria and yeast that communicate with and benefit from each other using small diffusible molecules. We explore the behavior of this heterogeneous microbial consortium, composed of Saccharomyces cerevisiae and Escherichia coli cells, using stochastic modeling. The stochastic model captures the relevant intra-cellular and inter-cellular interactions taking place in and between the eukaryotic and prokaryotic cells. Integration of well-characterized molecular regulatory elements into these two microbes allows for communication through quorum sensing. A gene controlling growth in yeast is induced by bacteria via chemical signals and vice versa. Interesting dynamics that are common in natural ecosystems, such as obligatory and facultative mutualism, extinction, commensalism and predator-prey like dynamics are observed. We investigate and report on the conditions under which the two species can successfully communicate and rescue each other. Conclusions This study explores the various behaviors exhibited by the cohabitation of engineered yeast and bacterial cells. The way that the model is built allows for studying the dynamics of any system consisting of two species communicating with one another via chemical signals. Therefore, key information acquired by our model may potentially drive the experimental design of various synthetic heterogeneous ecosystems. PMID:22672814

Electrochemical H2O2 biosensor composed of myoglobin on MoS2 nanoparticle-graphene oxide hybrid structure.

PubMed

Yoon, Jinho; Lee, Taek; Bapurao G, Bharate; Jo, Jinhee; Oh, Byung-Keun; Choi, Jeong-Woo

2017-07-15

In this research, the electrochemical biosensor composed of myoglobin (Mb) on molybdenum disulfide nanoparticles (MoS 2 NP) encapsulated with graphene oxide (GO) was fabricated for the detection of hydrogen peroxide (H 2 O 2 ). Hybrid structure composed of MoS 2 NP and GO (GO@MoS 2 ) was fabricated for the first time to enhance the electrochemical signal of the biosensor. As a sensing material, Mb was introduced to fabricate the biosensor for H 2 O 2 detection. Formation and immobilization of GO@MoS 2 was confirmed by transmission electron microscopy, ultraviolet-visible spectroscopy, scanning electron microscopy, and scanning tunneling microscopy. Immobilization of Mb, and electrochemical property of biosensor were investigated by cyclic voltammetry and amperometric i-t measurements. Fabricated biosensor showed the electrochemical signal enhanced redox current as -1.86μA at an oxidation potential and 1.95μA at a reduction potential that were enhanced relative to those of electrode prepared without GO@MoS 2 . Also, this biosensor showed the reproducibility of electrochemical signal, and retained the property until 9 days from fabrication. Upon addition of H 2 O 2 , the biosensor showed enhanced amperometric response current with selectivity relative to that of the biosensor prepared without GO@MoS 2 . This novel hybrid material-based biosensor can suggest a milestone in the development of a highly sensitive detecting platform for biosensor fabrication with highly sensitive detection of target molecules other than H 2 O 2 . Copyright © 2016 Elsevier B.V. All rights reserved.

[A novel biologic electricity signal measurement based on neuron chip].

PubMed

Lei, Yinsheng; Wang, Mingshi; Sun, Tongjing; Zhu, Qiang; Qin, Ran

2006-06-01

Neuron chip is a multiprocessor with three pipeline CPU; its communication protocol and control processor are integrated in effect to carry out the function of communication, control, attemper, I/O, etc. A novel biologic electronic signal measurement network system is composed of intelligent measurement nodes with neuron chip at the core. In this study, the electronic signals such as ECG, EEG, EMG and BOS can be synthetically measured by those intelligent nodes, and some valuable diagnostic messages are found. Wavelet transform is employed in this system to analyze various biologic electronic signals due to its strong time-frequency ability of decomposing signal local character. Better effect is gained. This paper introduces the hardware structure of network and intelligent measurement node, the measurement theory and the signal figure of data acquisition and processing.

Termination of aquired and natural immunological tolerance with specific complexes

PubMed Central

1975-01-01

It was possible to terminate the induced unresponsive state to bovine serum albumin (BSA) and the natural unresponsive state to autologous thyroglobulin in rabbits (RTg) by immunization with complexes composed of heterologous cross-reacting antibody and the tolerated antigens. The unresponsive state was terminated in rabbits made unresponsive by neonatal injections of BSA and then 3 mo later injected with complexes composed of BSA and guinea pig antihuman serum albumin. This termination was manifested by the presence of anti-BSA plaque-forming cells. Similarly, the natural unresponsive state was terminated in adult rabbits injected with complexes between RTg and guinea pig antibovine thyroglobulin (BTg) in that thyroid lesions and circulating anti-RTg were produced. The results can be best explained by the presence of unresponsive T cells and competent B cells, where the guinea pig gamma globulin (antibody) activates T cells specific for the guinea pig gamma globulin portion of the complexes and thus permits stimulation of B cells competent to the exposed determinants of the tolerated (BSA or RTg) portion of the complexes. The detailed mechanism for the activation of B cells in tolerant animals is discussed. PMID:1095680

Use of Global Positioning System for the capture of environmental data.

DOT National Transportation Integrated Search

1995-01-01

The purpose of this study was to determine the feasibility of using the Global Positioning System (GPS), composed of 24 NAVSTAR satellites emitting individually coded radio signals with accurate timing and ephemeris information, to capture environmen...

Pulse stretcher for narrow pulses

NASA Technical Reports Server (NTRS)

Lindsey, R. S., Jr. (Inventor)

1974-01-01

A pulse stretcher for narrow pulses is presented. The stretcher is composed of an analog section for processing each arriving analog pulse and a digital section with logic for providing command signals to the gates and switches in the analog section.

Absolute detector calibration using twin beams.

PubMed

Peřina, Jan; Haderka, Ondřej; Michálek, Václav; Hamar, Martin

2012-07-01

A method for the determination of absolute quantum detection efficiency is suggested based on the measurement of photocount statistics of twin beams. The measured histograms of joint signal-idler photocount statistics allow us to eliminate an additional noise superimposed on an ideal calibration field composed of only photon pairs. This makes the method superior above other approaches presently used. Twin beams are described using a paired variant of quantum superposition of signal and noise.

Enhanced Critical Care Air Transport Team Training for Mitigation of Task Saturation

DTIC Science & Technology

2013-03-01

specialized members (physician, critical care nurse , and respiratory therapist) trained to handle the complex, critical nature of patients in hemodynamic ...with complex medical conditions have been poorly studied. 3.0 BACKGROUND Teams are composed of three medical personnel (a physician, a nurse , and

Biogenesis of the yeast cytochrome bc1 complex.

PubMed

Zara, Vincenzo; Conte, Laura; Trumpower, Bernard L

2009-01-01

The mitochondrial respiratory chain is composed of four different protein complexes that cooperate in electron transfer and proton pumping across the inner mitochondrial membrane. The cytochrome bc1 complex, or complex III, is a component of the mitochondrial respiratory chain. This review will focus on the biogenesis of the bc1 complex in the mitochondria of the yeast Saccharomyces cerevisiae. In wild type yeast mitochondrial membranes the major part of the cytochrome bc1 complex was found in association with one or two copies of the cytochrome c oxidase complex. The analysis of several yeast mutant strains in which single genes or pairs of genes encoding bc1 subunits had been deleted revealed the presence of a common set of bc1 sub-complexes. These sub-complexes are represented by the central core of the bc1 complex, consisting of cytochrome b bound to subunit 7 and subunit 8, by the two core proteins associated with each other, by the Rieske protein associated with subunit 9, and by those deriving from the unexpected interaction of each of the two core proteins with cytochrome c1. Furthermore, a higher molecular mass sub-complex is that composed of cytochrome b, cytochrome c1, core protein 1 and 2, subunit 6, subunit 7 and subunit 8. The identification and characterization of all these sub-complexes may help in defining the steps and the molecular events leading to bc1 assembly in yeast mitochondria.

On the Origin of Complex Adaptive Traits: Progress Since the Darwin Versus Mivart Debate.

PubMed

Suzuki, Takao K

2017-06-01

The evolutionary origin of complex adaptive traits has been a controversial topic in the history of evolutionary biology. Although Darwin argued for the gradual origins of complex adaptive traits within the theory of natural selection, Mivart insisted that natural selection could not account for the incipient stages of complex traits. The debate starting from Darwin and Mivart eventually engendered two opposite views: gradualism and saltationism. Although this has been a long-standing debate, the issue remains unresolved. However, recent studies have interrogated classic examples of complex traits, such as the asymmetrical eyes of flatfishes and leaf mimicry of butterfly wings, whose origins were debated by Darwin and Mivart. Here, I review recent findings as a starting point to provide a modern picture of the evolution of complex adaptive traits. First, I summarize the empirical evidence that unveils the evolutionary steps toward complex traits. I then argue that the evolution of complex traits could be understood within the concept of "reducible complexity." Through these discussions, I propose a conceptual framework for the formation of complex traits, named as reducible-composable multicomponent systems, that satisfy two major characteristics: reducibility into a sum of subcomponents and composability to construct traits from various additional and combinatorial arrangements of the subcomponents. This conceptual framework provides an analytical foundation for exploring evolutionary pathways to build up complex traits. This review provides certain essential avenues for deciphering the origin of complex adaptive traits. © 2017 Wiley Periodicals, Inc.

Modulation of EEG Theta Band Signal Complexity by Music Therapy

NASA Astrophysics Data System (ADS)

Bhattacharya, Joydeep; Lee, Eun-Jeong

The primary goal of this study was to investigate the impact of monochord (MC) sounds, a type of archaic sounds used in music therapy, on the neural complexity of EEG signals obtained from patients undergoing chemotherapy. The secondary goal was to compare the EEG signal complexity values for monochords with those for progressive muscle relaxation (PMR), an alternative therapy for relaxation. Forty cancer patients were randomly allocated to one of the two relaxation groups, MC and PMR, over a period of six months; continuous EEG signals were recorded during the first and last sessions. EEG signals were analyzed by applying signal mode complexity, a measure of complexity of neuronal oscillations. Across sessions, both groups showed a modulation of complexity of beta-2 band (20-29Hz) at midfrontal regions, but only MC group showed a modulation of complexity of theta band (3.5-7.5Hz) at posterior regions. Therefore, the neuronal complexity patterns showed different changes in EEG frequency band specific complexity resulting in two different types of interventions. Moreover, the different neural responses to listening to monochords and PMR were observed after regular relaxation interventions over a short time span.

NMR and MALDI-TOF MS based characterization of exopolysaccharides in anaerobic microbial aggregates from full-scale reactors

PubMed Central

Gonzalez-Gil, Graciela; Thomas, Ludivine; Emwas, Abdul-Hamid; Lens, Piet N. L.; Saikaly, Pascal E.

2015-01-01

Anaerobic granular sludge is composed of multispecies microbial aggregates embedded in a matrix of extracellular polymeric substances (EPS). Here we characterized the chemical fingerprint of the polysaccharide fraction of EPS in anaerobic granules obtained from full-scale reactors treating different types of wastewater. Nuclear magnetic resonance (NMR) signals of the polysaccharide region from the granules were very complex, likely as a result of the diverse microbial population in the granules. Using nonmetric multidimensional scaling (NMDS), the 1H NMR signals of reference polysaccharides (gellan, xanthan, alginate) and those of the anaerobic granules revealed that there were similarities between the polysaccharides extracted from granules and the reference polysaccharide alginate. Further analysis of the exopolysaccharides from anaerobic granules, and reference polysaccharides using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) revealed that exopolysaccharides from two of the anaerobic granular sludges studied exhibited spectra similar to that of alginate. The presence of sequences related to the synthesis of alginate was confirmed in the metagenomes of the granules. Collectively these results suggest that alginate-like exopolysaccharides are constituents of the EPS matrix in anaerobic granular sludge treating different industrial wastewater. This finding expands the engineered environments where alginate has been found as EPS constituent of microbial aggregates. PMID:26391984

Targeted delivery of CD44s-siRNA by ScFv overcomes de novo resistance to cetuximab in triple negative breast cancer.

PubMed

Fu, Wenyan; Sun, Hefen; Zhao, Yang; Chen, Mengting; Yang, Lipeng; Yang, Xueli; Jin, Wei

2018-05-16

The overexpression of EGFR often occurs in TNBC, and the anti-EGFR receptor antibody cetuximab is used widely to treat metastatic cancer in the clinic. However, EGFR-targeted therapies have been developed for TNBC without clinical success. In this study, we show that impaired EGFR degradation is crucial for resistance to cetuximab, which depends on the cell surface molecule CD44. To further investigate the role of CD44 in EGFR signaling and its treatment potential, we developed a targeting fusion protein composed of an anti-EGFR scFv generated from cetuximab and truncated protamine, called Ce-tP. CD44 siRNA can be specifically delivered into EGFR-positive TNBC cells by Ce-tP. Efficient knockdown of CD44 and suppression of both EGFR and downstream signaling by the Ce-tP/siRNA complex were observed in EGFR-positive TNBC cells. More importantly, our results also showed that targeted delivery of siRNA specific for CD44 can efficiently overcome resistance to EGFR targeting in TNBC cells both in vitro and in vivo. Overall, our results establish a new principle to achieve EGFR inhibition in TNBC and limit drug resistance. Copyright © 2018 Elsevier Ltd. All rights reserved.

Detection of social group instability among captive rhesus macaques using joint network modeling

PubMed Central

Beisner, Brianne A.; Jin, Jian; Fushing, Hsieh; Mccowan, Brenda

2015-01-01

Social stability in group-living animals is an emergent property which arises from the interaction amongst multiple behavioral networks. However, pinpointing when a social group is at risk of collapse is difficult. We used a joint network modeling approach to examine the interdependencies between two behavioral networks, aggression and status signaling, from four stable and three unstable groups of rhesus macaques in order to identify characteristic patterns of network interdependence in stable groups that are readily distinguishable from unstable groups. Our results showed that the most prominent source of aggression-status network interdependence in stable social groups came from more frequent dyads than expected with opposite direction status-aggression (i.e. A threatens B and B signals acceptance of subordinate status). In contrast, unstable groups showed a decrease in opposite direction aggression-status dyads (but remained higher than expected) as well as more frequent than expected dyads with bidirectional aggression. These results demonstrate that not only was the stable joint relationship between aggression and status networks readily distinguishable from unstable time points, social instability manifested in at least two different ways. In sum, our joint modeling approach may prove useful in quantifying and monitoring the complex social dynamics of any wild or captive social system, as all social systems are composed of multiple interconnected networks PMID:26052339

The carboxyl-terminus directs TAF(I)48 to the nucleus and nucleolus and associates with multiple nuclear import receptors.

PubMed

Dynes, Joseph L; Xu, Shuping; Bothner, Sarah; Lahti, Jill M; Hori, Roderick T

2004-03-01

The protein complex Selectivity Factor 1, composed of TBP, TAF(I)48, TAF(I)63 and TAF(I)110, is required for rRNA transcription by RNA polymerase I in the nucleolus. The steps involved in targeting Selectivity Factor 1 will be dependent on the transport pathways that are used and the localization signals that direct this trafficking. In order to investigate these issues, we characterized human TAF(I)48, a subunit of Selectivity Factor 1. By domain analysis of TAF(I)48, the carboxyl-terminal 51 residues were found to be required for the localization of TAF(I)48, as well as sufficient to direct Green Fluorescent Protein to the nucleus and nucleolus. The carboxyl-terminus of TAF(I)48 also has the ability to associate with multiple members of the beta-karyopherin family of nuclear import receptors, including importin beta (karyopherin beta1), transportin (karyopherin beta2) and RanBP5 (karyopherin beta3), in a Ran-dependent manner. This property of interacting with multiple beta-karyopherins has been previously reported for the nuclear localization signals of some ribosomal proteins that are likewise directed to the nucleolus. This study identifies the first nuclear import sequence identified within the TBP-Associated Factor subunits of Selectivity Factor 1.

NMR and MALDI-TOF MS based characterization of exopolysaccharides in anaerobic microbial aggregates from full-scale reactors.

PubMed

Gonzalez-Gil, Graciela; Thomas, Ludivine; Emwas, Abdul-Hamid; Lens, Piet N L; Saikaly, Pascal E

2015-09-22

Anaerobic granular sludge is composed of multispecies microbial aggregates embedded in a matrix of extracellular polymeric substances (EPS). Here we characterized the chemical fingerprint of the polysaccharide fraction of EPS in anaerobic granules obtained from full-scale reactors treating different types of wastewater. Nuclear magnetic resonance (NMR) signals of the polysaccharide region from the granules were very complex, likely as a result of the diverse microbial population in the granules. Using nonmetric multidimensional scaling (NMDS), the (1)H NMR signals of reference polysaccharides (gellan, xanthan, alginate) and those of the anaerobic granules revealed that there were similarities between the polysaccharides extracted from granules and the reference polysaccharide alginate. Further analysis of the exopolysaccharides from anaerobic granules, and reference polysaccharides using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) revealed that exopolysaccharides from two of the anaerobic granular sludges studied exhibited spectra similar to that of alginate. The presence of sequences related to the synthesis of alginate was confirmed in the metagenomes of the granules. Collectively these results suggest that alginate-like exopolysaccharides are constituents of the EPS matrix in anaerobic granular sludge treating different industrial wastewater. This finding expands the engineered environments where alginate has been found as EPS constituent of microbial aggregates.

Boosting the signal: Endothelial inward rectifier K+ channels.

PubMed

Jackson, William F

2017-04-01

Endothelial cells express a diverse array of ion channels including members of the strong inward rectifier family composed of K IR 2 subunits. These two-membrane spanning domain channels are modulated by their lipid environment, and exist in macromolecular signaling complexes with receptors, protein kinases and other ion channels. Inward rectifier K + channel (K IR ) currents display a region of negative slope conductance at membrane potentials positive to the K + equilibrium potential that allows outward current through the channels to be activated by membrane hyperpolarization, permitting K IR to amplify hyperpolarization induced by other K + channels and ion transporters. Increases in extracellular K + concentration activate K IR allowing them to sense extracellular K + concentration and transduce this change into membrane hyperpolarization. These properties position K IR to participate in the mechanism of action of hyperpolarizing vasodilators and contribute to cell-cell conduction of hyperpolarization along the wall of microvessels. The expression of K IR in capillaries in electrically active tissues may allow K IR to sense extracellular K + , contributing to functional hyperemia. Understanding the regulation of expression and function of microvascular endothelial K IR will improve our understanding of the control of blood flow in the microcirculation in health and disease and may provide new targets for the development of therapeutics in the future. © 2016 John Wiley & Sons Ltd.

An Ultrasensitive Electrochemical Immunosensor for Alpha-Fetoprotein Using an Envision Complex-Antibody Copolymer as a Sensitive Label

PubMed Central

Xiong, Ping; Gan, Ning; Cao, Yuting; Hu, Futao; Li, Tianhua; Zheng, Lei

2012-01-01

A novel strategy is presented for sensitive detection of alfa-fetoprotein (AFP), using a horseradish peroxidase (HRP)-functionalized Envision antibody complex (EVC) as the label. The Envision-AFP signal antibody copolymer (EVC-AFP Ab2) was composed of a dextran amine skeleton anchoring more than 100 molecules of HRP and 15 molecules of secondary antibody, and acted as a signal tag in the immunosensor. The sensor was constructed using the following steps: First, gold electrode (GE) was modified with nano-gold (AuNPs) by electro-deposition in HAuCl4 solution. The high affinity of the AuNPs surface facilitates direct formation of a self-assembled thiolated protein G layer. Next, the coated GE was incubated in a solution of AFP capture antibody (AFP Ab1); these antibodies attach to the thiolated protein G layer through their non-antigenic regions, leaving the antigen binding sites for binding of target analyte. Following a sandwich immunoreaction, an EVC-AFP Ab2-AFP-AFP Ab1 immunocomplex was formed on the electrode surface, allowing large amounts of HRP on the complex to produce an amplified electrocatalytic current of hydroquinone (HQ) in the presence of hydrogen peroxide (H2O2). Highly amplified detection was achieved, with a detection limit of 2 pg/mL and a linear range of 0.005–0.2 ng/mL for AFP in 10 μL undiluted serum; this is near or below the normal levels of most cancer biomarker proteins in human serum. Measurements of AFP in the serum of cancer patients correlated strongly with standard enzyme-linked immunosorbent assays. These easily fabricated EVC-modified immunosensors show excellent promise for future fabrication of bioelectronic arrays. By varying the target biomolecules, this technique may be easily extended for use with other immunoassays, and thus represents a versatile design route.

Different stabilities of liposomes containing saturated and unsaturated lipids toward the addition of cyclodextrins.

PubMed

Ikeda, Atsushi; Funada, Rikushi; Sugikawa, Kouta

2016-06-14

Liposomes composed of unsaturated lipids were more stable than those containing saturated lipids toward DMe-β-CDx, DMe-α-CDx and DMe-β-CDx. The Hill coefficient values (n) indicated that the saturated lipid·DMe-CDx complexes had stoichiometric ratios in the range of 1 : 3-1 : 4, while the unsaturated lipid·DMe-CDx complexes had ratios in the range of 1 : 1.5-1 : 3. That is, a cis alkene group in the unsaturated lipids prevented complexation with a second DMe-CDx in the direction toward each acyl chain. Furthermore, the liposomes composed of the unsaturated lipids were much slower to form precipitates upon the addition of α-CDx than those of the saturated lipids. To the best of our knowledge, this is the first example showing that CDxs interact with unsaturated lipids.

Paucity of attractors in nonlinear systems driven with complex signals.

PubMed

Pethel, Shawn D; Blakely, Jonathan N

2011-04-01

We study the probability of multistability in a quadratic map driven repeatedly by a random signal of length N, where N is taken as a measure of the signal complexity. We first establish analytically that the number of coexisting attractors is bounded above by N. We then numerically estimate the probability p of a randomly chosen signal resulting in a multistable response as a function of N. Interestingly, with increasing drive signal complexity the system exhibits a paucity of attractors. That is, almost any drive signal beyond a certain complexity level will result in a single attractor response (p=0). This mechanism may play a role in allowing sensitive multistable systems to respond consistently to external influences.

2-O Heparan Sulfate Sulfation by Hs2st Is Required for Erk/Mapk Signalling Activation at the Mid-Gestational Mouse Telencephalic Midline

PubMed Central

Chan, Wai Kit; Howe, Katherine; Clegg, James M.; Guimond, Scott E.; Price, David J.; Turnbull, Jeremy E.; Pratt, Thomas

2015-01-01

Heparan sulfate (HS) is a linear carbohydrate composed of polymerized uronate-glucosamine disaccharide units that decorates cell surface and secreted glycoproteins in the extracellular matrix. In mammals HS is subjected to differential sulfation by fifteen different heparan sulfotransferase (HST) enzymes of which Hs2st uniquely catalyzes the sulfation of the 2-O position of the uronate in HS. HS sulfation is postulated to be important for regulation of signaling pathways by facilitating the interaction of HS with signaling proteins including those of the Fibroblast Growth Factor (Fgf) family which signal through phosphorylation of extracellular signal-regulated kinases Erk1/2. In the developing mouse telencephalon Fgf2 signaling regulates proliferation and neurogenesis. Loss of Hs2st function phenocopies the thinned cerebral cortex of mutant mice in which Fgf2 or Erk1/2 function are abrogated, suggesting the hypothesis that 2-O-sulfated HS structures play a specific role in Fgf2/Erk signaling pathway in this context in vivo. This study investigated the molecular role of 2-O sulfation in Fgf2/Erk signaling in the developing telencephalic midline midway through mouse embryogenesis at E12.5. We examined the expression of Hs2st, Fgf2, and Erk1/2 activity in wild-type and Hs2st-/- mice. We found that Hs2st is expressed at high levels at the midline correlating with high levels of Erk1/2 activation and Erk1/2 activation was drastically reduced in the Hs2st-/- mutant at the rostral telencephalic midline. We also found that 2-O sulfation is specifically required for the binding of Fgf2 protein to Fgfr1, its major cell-surface receptor at the rostral telencephalic midline. We conclude that 2-O sulfated HS structures generated by Hs2st are needed to form productive signaling complexes between HS, Fgf2 and Fgfr1 that activate Erk1/2 at the midline. Overall, our data suggest the interesting possibility that differential expression of Hs2st targets the rostral telencephalic midline for high levels of Erk signaling by increasing the sensitivity of cells to an Fgf2 signal that is rather more widespread. PMID:26075383

A century old renin-angiotensin system still grows with endless possibilities: AT1 receptor signaling cascades in cardiovascular physiopathology.

PubMed

Balakumar, Pitchai; Jagadeesh, Gowraganahalli

2014-10-01

Ang II, the primary effector pleiotropic hormone of the renin-angiotensin system (RAS) cascade, mediates physiological control of blood pressure and electrolyte balance through its action on vascular tone, aldosterone secretion, renal sodium absorption, water intake, sympathetic activity and vasopressin release. It affects the function of most of the organs far beyond blood pressure control including heart, blood vessels, kidney and brain, thus, causing both beneficial and deleterious effects. However, the protective axis of the RAS composed of ACE2, Ang (1-7), alamandine, and Mas and MargD receptors might oppose some harmful effects of Ang II and might promote beneficial cardiovascular effects. Newly identified RAS family peptides, Ang A and angioprotectin, further extend the complexities in understanding the cardiovascular physiopathology of RAS. Most of the diverse actions of Ang II are mediated by AT1 receptors, which couple to classical Gq/11 protein and activate multiple downstream signals, including PKC, ERK1/2, Raf, tyrosine kinases, receptor tyrosine kinases (EGFR, PDGF, insulin receptor), nuclear factor κB and reactive oxygen species (ROS). Receptor activation via G12/13 stimulates Rho-kinase, which causes vascular contraction and hypertrophy. The AT1 receptor activation also stimulates G protein-independent signaling pathways such as β-arrestin-mediated MAPK activation and Src-JAK/STAT. AT1 receptor-mediated activation of NADPH oxidase releases ROS, resulting in the activation of pro-inflammatory transcription factors and stimulation of small G proteins such as Ras, Rac and RhoA. The components of the RAS and the major Ang II-induced signaling cascades of AT1 receptors are reviewed. Copyright © 2014 Elsevier Inc. All rights reserved.

Costimulatory receptors in a teleost fish: Typical CD28, elusive CTLA4

USGS Publications Warehouse

Bernard, D.; Riteau, B.; Hansen, J.D.; Phillips, R.B.; Michel, F.; Boudinot, P.; Benmansour, A.

2006-01-01

T cell activation requires both specific recognition of the peptide-MHC complex by the TCR and additional signals delivered by costimulatory receptors. We have identified rainbow trout sequences similar to CD28 (rbtCD28) and CTLA4 (rbtCTLA4). rbtCD28 and rbtCTLA4 are composed of an extracellular Ig-superfamily V domain, a transmembrane region, and a cytoplasmic tail. The presence of a conserved ligand binding site within the V domain of both molecules suggests that these receptors likely recognize the fish homologues of the B7 family. The mRNA expression pattern of rbtCD28 and rbtCTLA4 in naive trout is reminiscent to that reported in humans and mice, because rbtCTLA4 expression within trout leukocytes was quickly up-regulated following PHA stimulation and virus infection. The cytoplasmic tail of rbtCD28 possesses a typical motif that is conserved in mammalian costimulatory receptors for signaling purposes. A chimeric receptor made of the extracellular domain of human CD28 fused to the cytoplasmic tail of rbtCD28 promoted TCR-induced IL-2 production in a human T cell line, indicating that rbtCD28 is indeed a positive costimulator. The cytoplasmic tail of rtrtCTLA4 lacked obvious signaling motifs and accordingly failed to signal when fused to the huCD28 extracellular domain. Interestingly, rbtCTLA4 and rbtCD28 are not positioned on the same chromosome and thus do not belong to a unique costimulatory cluster as in mammals. Finally, oar results raise questions about the origin and evolution of positive and negative costimulation in vertebrate immune systems. Copyright ?? 2006 by The American Association of Immunologists, Inc.

Analysis of the Influence of Complexity and Entropy of Odorant on Fractal Dynamics and Entropy of EEG Signal.

PubMed

Namazi, Hamidreza; Akrami, Amin; Nazeri, Sina; Kulish, Vladimir V

2016-01-01

An important challenge in brain research is to make out the relation between the features of olfactory stimuli and the electroencephalogram (EEG) signal. Yet, no one has discovered any relation between the structures of olfactory stimuli and the EEG signal. This study investigates the relation between the structures of EEG signal and the olfactory stimulus (odorant). We show that the complexity of the EEG signal is coupled with the molecular complexity of the odorant, where more structurally complex odorant causes less fractal EEG signal. Also, odorant having higher entropy causes the EEG signal to have lower approximate entropy. The method discussed here can be applied and investigated in case of patients with brain diseases as the rehabilitation purpose.

Analysis of the Influence of Complexity and Entropy of Odorant on Fractal Dynamics and Entropy of EEG Signal

PubMed Central

Akrami, Amin; Nazeri, Sina

2016-01-01

An important challenge in brain research is to make out the relation between the features of olfactory stimuli and the electroencephalogram (EEG) signal. Yet, no one has discovered any relation between the structures of olfactory stimuli and the EEG signal. This study investigates the relation between the structures of EEG signal and the olfactory stimulus (odorant). We show that the complexity of the EEG signal is coupled with the molecular complexity of the odorant, where more structurally complex odorant causes less fractal EEG signal. Also, odorant having higher entropy causes the EEG signal to have lower approximate entropy. The method discussed here can be applied and investigated in case of patients with brain diseases as the rehabilitation purpose. PMID:27699169

Brain signal complexity rises with repetition suppression in visual learning.

PubMed

Lafontaine, Marc Philippe; Lacourse, Karine; Lina, Jean-Marc; McIntosh, Anthony R; Gosselin, Frédéric; Théoret, Hugo; Lippé, Sarah

2016-06-21

Neuronal activity associated with visual processing of an unfamiliar face gradually diminishes when it is viewed repeatedly. This process, known as repetition suppression (RS), is involved in the acquisition of familiarity. Current models suggest that RS results from interactions between visual information processing areas located in the occipito-temporal cortex and higher order areas, such as the dorsolateral prefrontal cortex (DLPFC). Brain signal complexity, which reflects information dynamics of cortical networks, has been shown to increase as unfamiliar faces become familiar. However, the complementarity of RS and increases in brain signal complexity have yet to be demonstrated within the same measurements. We hypothesized that RS and brain signal complexity increase occur simultaneously during learning of unfamiliar faces. Further, we expected alteration of DLPFC function by transcranial direct current stimulation (tDCS) to modulate RS and brain signal complexity over the occipito-temporal cortex. Participants underwent three tDCS conditions in random order: right anodal/left cathodal, right cathodal/left anodal and sham. Following tDCS, participants learned unfamiliar faces, while an electroencephalogram (EEG) was recorded. Results revealed RS over occipito-temporal electrode sites during learning, reflected by a decrease in signal energy, a measure of amplitude. Simultaneously, as signal energy decreased, brain signal complexity, as estimated with multiscale entropy (MSE), increased. In addition, prefrontal tDCS modulated brain signal complexity over the right occipito-temporal cortex during the first presentation of faces. These results suggest that although RS may reflect a brain mechanism essential to learning, complementary processes reflected by increases in brain signal complexity, may be instrumental in the acquisition of novel visual information. Such processes likely involve long-range coordinated activity between prefrontal and lower order visual areas. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Signaling complexes of voltage-gated calcium channels

PubMed Central

Turner, Ray W; Anderson, Dustin

2011-01-01

Voltage-gated calcium channels are key mediators of depolarization induced calcium entry into electrically excitable cells. There is increasing evidence that voltage-gated calcium channels, like many other types of ionic channels, do not operate in isolation, but instead form complexes with signaling molecules, G protein coupled receptors, and other types of ion channels. Furthermore, there appears to be bidirectional signaling within these protein complexes, thus allowing not only for efficient translation of calcium signals into cellular responses, but also for tight control of calcium entry per se. In this review, we will focus predominantly on signaling complexes between G protein-coupled receptors and high voltage activated calcium channels, and on complexes of voltage-gated calcium channels and members of the potassium channel superfamily. PMID:21832880

Element analysis: a wavelet-based method for analysing time-localized events in noisy time series

PubMed Central

2017-01-01

A method is derived for the quantitative analysis of signals that are composed of superpositions of isolated, time-localized ‘events’. Here, these events are taken to be well represented as rescaled and phase-rotated versions of generalized Morse wavelets, a broad family of continuous analytic functions. Analysing a signal composed of replicates of such a function using another Morse wavelet allows one to directly estimate the properties of events from the values of the wavelet transform at its own maxima. The distribution of events in general power-law noise is determined in order to establish significance based on an expected false detection rate. Finally, an expression for an event’s ‘region of influence’ within the wavelet transform permits the formation of a criterion for rejecting spurious maxima due to numerical artefacts or other unsuitable events. Signals can then be reconstructed based on a small number of isolated points on the time/scale plane. This method, termed element analysis, is applied to the identification of long-lived eddy structures in ocean currents as observed by along-track measurements of sea surface elevation from satellite altimetry. PMID:28484325

Complexation behavior of oppositely charged polyelectrolytes: Effect of charge distribution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Mingtian; Li, Baohui, E-mail: dliang@pku.edu.cn, E-mail: baohui@nankai.edu.cn; Zhou, Jihan

Complexation behavior of oppositely charged polyelectrolytes in a solution is investigated using a combination of computer simulations and experiments, focusing on the influence of polyelectrolyte charge distributions along the chains on the structure of the polyelectrolyte complexes. The simulations are performed using Monte Carlo with the replica-exchange algorithm for three model systems where each system is composed of a mixture of two types of oppositely charged model polyelectrolyte chains (EGEG){sub 5}/(KGKG){sub 5}, (EEGG){sub 5}/(KKGG){sub 5}, and (EEGG){sub 5}/(KGKG){sub 5}, in a solution including explicit solvent molecules. Among the three model systems, only the charge distributions along the chains are notmore » identical. Thermodynamic quantities are calculated as a function of temperature (or ionic strength), and the microscopic structures of complexes are examined. It is found that the three systems have different transition temperatures, and form complexes with different sizes, structures, and densities at a given temperature. Complex microscopic structures with an alternating arrangement of one monolayer of E/K monomers and one monolayer of G monomers, with one bilayer of E and K monomers and one bilayer of G monomers, and with a mixture of monolayer and bilayer of E/K monomers in a box shape and a trilayer of G monomers inside the box are obtained for the three mixture systems, respectively. The experiments are carried out for three systems where each is composed of a mixture of two types of oppositely charged peptide chains. Each peptide chain is composed of Lysine (K) and glycine (G) or glutamate (E) and G, in solution, and the chain length and amino acid sequences, and hence the charge distribution, are precisely controlled, and all of them are identical with those for the corresponding model chain. The complexation behavior and complex structures are characterized through laser light scattering and atomic force microscopy measurements. The order of the apparent weight-averaged molar mass and the order of density of complexes observed from the three experimental systems are qualitatively in agreement with those predicted from the simulations.« less

Putative members of the Arabidopsis Nup107-160 nuclear pore sub-complex contribute to pathogen defense.

PubMed

Wiermer, Marcel; Cheng, Yu Ti; Imkampe, Julia; Li, Meilan; Wang, Dongmei; Lipka, Volker; Li, Xin

2012-06-01

In eukaryotic cells, transduction of external stimuli into the nucleus to induce transcription and export of mRNAs for translation in the cytoplasm is mediated by nuclear pore complexes (NPCs) composed of nucleoporin proteins (Nups). We previously reported that Arabidopsis MOS3, encoding the homolog of vertebrate Nup96, is required for plant immunity and constitutive resistance mediated by the de-regulated Toll interleukin 1 receptor/nucleotide-binding/leucine-rich repeat (TNL)-type R gene snc1. In vertebrates, Nup96 is a component of the conserved Nup107-160 nuclear pore sub-complex, and implicated in immunity-related mRNA export. Here, we used a reverse genetics approach to examine the requirement for additional subunits of the predicted Arabidopsis Nup107-160 complex in plant immunity. We show that, among eight putative complex members, beside MOS3, only plants with defects in Nup160 or Seh1 are impaired in basal resistance. Constitutive resistance in the snc1 mutant and immunity mediated by TNL-type R genes also depend on functional Nup160 and have a partial requirement for Seh1. Conversely, resistance conferred by coiled coil-type immune receptors operates largely independently of both genes, demonstrating specific contributions to plant defense signaling. Our functional analysis further revealed that defects in nup160 and seh1 result in nuclear accumulation of poly(A) mRNA, and, in the case of nup160, considerable depletion of EDS1, a key positive regulator of basal and TNL-triggered resistance. These findings suggest that Nup160 is required for nuclear mRNA export and full expression of EDS1-conditioned resistance pathways in Arabidopsis. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.

Chiral SiO2 and Ag@SiO2 Materials Templated by Complexes Consisting of Comblike Polyethyleneimine and Tartaric Acid.

PubMed

Yao, Dong-Dong; Murata, Hiroki; Tsunega, Seiji; Jin, Ren-Hua

2015-10-26

A facile avenue to fabricate micrometer-sized chiral (L-, D-) and meso-like (dl-) SiO2 materials with unique structures by using crystalline complexes (cPEI/tart), composed of comblike polyethyleneimine (cPEI) and L-, D-, or dl-tartaric acid, respectively, as catalytic templates is reported. Interestingly, both chiral crystalline complexes appeared as regularly left- and right-twisted bundle structures about 10 μm in length and about 5 μm in diameter, whereas the dl-form occurred as circular structures with about 10 μm diameter. Subsequently, SiO2 @cPEI/tart hybrids with high silica content (>55.0 wt %) were prepared by stirring a mixture containing tetramethoxysilane (TMOS) and the aggregates of the crystalline complexes in water. The chiral SiO2 hybrids and calcined chiral SiO2 showed very strong CD signals and a nanofiber-based morphology on their surface, whereas dl-SiO2 showed no CD activity and a nanosheet-packed disklike shape. Furthermore, metallic silver nanoparticles (Ag NPs) were encapsulated in each silica hybrid to obtain chiral (D and L forms) and meso-like (dl form) Ag@SiO2 composites. Also, the reaction between L-cysteine (Lcys) and these Ag@SiO2 composites was preliminarily investigated. Only chiral L- and D-Ag@SiO2 composites promoted the reaction between Lcys and Ag NPs to produce a molecular [Ag-Lcys]n complex with remarkable exciton chirality, whereas the reaction hardly occurred in the case of meso-like (dl-) Ag@SiO2 composite. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

ATG13

PubMed Central

Alers, Sebastian; Wesselborg, Sebastian; Stork, Björn

2014-01-01

During the past 20 years, autophagy signaling has entered the main stage of the cell biological theater. Autophagy represents an intracellular degradation process that is involved in both the bulk recycling of cytoplasmic components and the selective removal of organelles, protein aggregates, or intracellular pathogens. The understanding of autophagy has been greatly facilitated by the characterization of the molecular machinery governing this process. In yeast, initiation of autophagy is controlled by the Atg1 kinase complex, which is composed of the Ser/Thr kinase Atg1, the adaptor protein Atg13, and the ternary complex of Atg17-Atg31-Atg29. In vertebrates, the orthologous ULK1 kinase complex contains the Ser/Thr kinase ULK1 and the accessory proteins ATG13, RB1CC1, and ATG101. Among these components, Atg1/ULK1 have gained major attention in the past, i.e., for the identification of upstream regulatory kinases, the characterization of downstream substrates controlling the autophagic flux, or as a druggable target for the modulation of autophagy. However, accumulating data indicate that the function of Atg13/ATG13 has been likely underestimated so far. In addition to ensuring proper Atg1/ULK1 recruitment and activity, this adaptor molecule has been implicated in ULK1-independent autophagy processes. Furthermore, recent data have identified additional binding partners of Atg13/ATG13 besides the components of the Atg1/ULK1 complex, e.g., Atg8 family proteins or acidic phospholipids. Therefore, in this review we will center the spotlight on Atg13/ATG13 and summarize the role that Atg13/ATG13 assumes in the autophagy stage play. PMID:24879146

Preliminary fabrication and characterization of low-leakage hybrid coaxial cable

NASA Astrophysics Data System (ADS)

Rudnitsky, Arkady; Elbaz, David; Zalevsky, Zeev

2013-10-01

In this paper we present the fabrication and the initial characterization of a new type of coaxial cable having reduced leakage characteristics and the capability of transmitting optical signals, in additional to the RF signal, through the glass medium between the metallic conductors. The suggested decreased leakage and material loss is obtained by using different metallic shield geometry. The suggested model is composed of a central conductor surrounded by plurality of metallic wires circularly disposed.

Polymorphisms in CTNNBL1 in relation to colorectal cancer with evolutionary implications

PubMed Central

Huhn, Stefanie; Ingelfinger, Dierk; Bermejo, Justo Lorenzo; Bevier, Melanie; Pardini, Barbara; Naccarati, Alessio; Steinke, Verena; Rahner, Nils; Holinski-Feder, Elke; Morak, Monika; Schackert, Hans K; Görgens, Heike; Pox, Christian P; Goecke, Timm; Kloor, Matthias; Loeffler, Markus; Büttner, Reinhard; Vodickova, Ludmila; Novotny, Jan; Demir, Kubilay; Cruciat, Cristina-Maria; Renneberg, Rebecca; Huber, Wolfgang; Niehrs, Christof; Boutros, Michael; Propping, Peter; Vodička, Pavel; Hemminki, Kari; Försti, Asta

2011-01-01

Colorectal cancer (CRC) is a complex disease related to environmental and genetic risk factors. Several studies have shown that susceptibility to complex diseases can be mediated by ancestral alleles. Using RNAi screening, CTNNBL1 was identified as a putative regulator of the Wnt signaling pathway, which plays a key role in colorectal carcinogenesis. Recently, single nucleotide polymorphisms (SNPs) in CTNNBL1 have been associated with obesity, a known risk factor for CRC. We investigated whether genetic variation in CTNNBL1 affects susceptibility to CRC and tested for signals of recent selection. We applied a tagging SNP approach that cover all known common variation in CTNNBL1 (allele frequency >5%; r2>0.8). A case-control study was carried out using two well-characterized study populations: a hospital-based Czech population composed of 751 sporadic cases and 755 controls and a family/early onset-based German population (697 cases and 644 controls). Genotyping was performed using allele specific PCR based TaqMan® assays (Applied Biosystems, Weiterstadt, Germany). In the Czech cohort, containing sporadic cases, the ancestral alleles of three SNPs showed evidence of association with CRC: rs2344481 (OR 1.44, 95%CI 1.06-1.95, dominant model), rs2281148 (OR 0.59, 95%CI 0.36-0.96, dominant model) and rs2235460 (OR 1.38, 95%CI 1.01-1.89, AA vs. GG). The associations were less prominent in the family/early onset-based German cohort. Data derived from several databases and statistical tests consistently pointed to a likely shaping of CTNNBL1 by positive selection. Further studies are needed to identify the actual function of CTNNBL1 and to validate the association results in other populations. PMID:21537400

PEBP1, a RAF kinase inhibitory protein, negatively regulates starvation-induced autophagy by direct interaction with LC3.

PubMed

Noh, Hae Sook; Hah, Young-Sool; Zada, Sahib; Ha, Ji Hye; Sim, Gyujin; Hwang, Jin Seok; Lai, Trang Huyen; Nguyen, Huynh Quoc; Park, Jae-Yong; Kim, Hyun Joon; Byun, June-Ho; Hahm, Jong Ryeal; Kang, Kee Ryeon; Kim, Deok Ryong

2016-11-01

Autophagy plays a critical role in maintaining cell homeostasis in response to various stressors through protein conjugation and activation of lysosome-dependent degradation. MAP1LC3B/LC3B (microtubule- associated protein 1 light chain 3 β) is conjugated with phosphatidylethanolamine (PE) in the membranes and regulates initiation of autophagy through interaction with many autophagy-related proteins possessing an LC3-interacting region (LIR) motif, which is composed of 2 hydrophobic amino acids (tryptophan and leucine) separated by 2 non-conserved amino acids (WXXL). In this study, we identified a new putative LIR motif in PEBP1/RKIP (phosphatidylethanolamine binding protein 1) that was originally isolated as a PE-binding protein and also a cellular inhibitor of MAPK/ERK signaling. PEBP1 was specifically bound to PE-unconjugated LC3 in cells, and mutation (WXXL mutated to AXXA) of this LIR motif disrupted its interaction with LC3 proteins. Interestingly, overexpression of PEBP1 significantly inhibited starvation-induced autophagy by activating the AKT and MTORC1 (mechanistic target of rapamycin [serine/threonine kinase] complex 1) signaling pathway and consequently suppressing the ULK1 (unc-51 like autophagy activating kinase 1) activity. In contrast, ablation of PEBP1 expression dramatically promoted the autophagic process under starvation conditions. Furthermore, PEBP1 lacking the LIR motif highly stimulated starvation-induced autophagy through the AKT-MTORC1-dependent pathway. PEBP1 phosphorylation at Ser153 caused dissociation of LC3 from the PEBP1-LC3 complex for autophagy induction. PEBP1-dependent suppression of autophagy was not associated with the MAPK pathway. These findings suggest that PEBP1 can act as a negative mediator in autophagy through stimulation of the AKT-MTORC1 pathway and direct interaction with LC3.

Amino Acid Availability Modulates Vacuolar H+-ATPase Assembly*

PubMed Central

Stransky, Laura A.; Forgac, Michael

2015-01-01

The vacuolar H+-ATPase (V-ATPase) is an ATP-dependent proton pump composed of a peripheral ATPase domain (V1) and a membrane-integral proton-translocating domain (V0) and is involved in many normal and disease processes. An important mechanism of regulating V-ATPase activity is reversible assembly of the V1 and V0 domains. Increased assembly in mammalian cells occurs under various conditions and has been shown to involve PI3K. The V-ATPase is necessary for amino acid-induced activation of mechanistic target of rapamycin complex 1 (mTORC1), which is important in controlling cell growth in response to nutrient availability and growth signals. The V-ATPase undergoes amino acid-dependent interactions with the Ragulator complex, which is involved in recruitment of mTORC1 to the lysosomal membrane during amino acid sensing. We hypothesized that changes in the V-ATPase/Ragulator interaction might involve amino acid-dependent changes in V-ATPase assembly. To test this, we measured V-ATPase assembly by cell fractionation in HEK293T cells treated with and without amino acids. V-ATPase assembly increases upon amino acid starvation, and this effect is reversed upon readdition of amino acids. Lysosomes from amino acid-starved cells possess greater V-ATPase-dependent proton transport, indicating that assembled pumps are catalytically active. Amino acid-dependent changes in both V-ATPase assembly and activity are independent of PI3K and mTORC1 activity, indicating the involvement of signaling pathways distinct from those implicated previously in controlling assembly. By contrast, lysosomal neutralization blocks the amino acid-dependent change in assembly and reactivation of mTORC1 after amino acid starvation. These results identify an important new stimulus for controlling V-ATPase assembly. PMID:26378229

Perimetric Complexity of Binary Digital Images: Notes on Calculation and Relation to Visual Complexity

NASA Technical Reports Server (NTRS)

Watson, Andrew B.

2011-01-01

Perimetric complexity is a measure of the complexity of binary pictures. It is defined as the sum of inside and outside perimeters of the foreground, squared, divided by the foreground area, divided by 4p . Difficulties arise when this definition is applied to digital images composed of binary pixels. In this paper we identify these problems and propose solutions. Perimetric complexity is often used as a measure of visual complexity, in which case it should take into account the limited resolution of the visual system. We propose a measure of visual perimetric complexity that meets this requirement.

THE BIOLOGICAL ACTIVITY OF SOLUBLE ANTIGEN-ANTIBODY COMPLEXES

PubMed Central

Ishizaka, Kimishige; Ishizaka, Teruko; Campbell, Dan H.

1959-01-01

Soluble BSA-anti-BSA complexes, formed in antigen excess, give immediate skin reactions in normal guinea pigs. The mechanism of the reaction is not that of passive or reversed passive anaphylaxis. The complex itself is toxic. Skin activity of the complex depends on its composition. It has become obvious that the complex composed of two antigen molecules and one antibody molecule, (Ag2Ab), does not have the activity, whereas, Ag3Ab2 and more complicated complexes do. The role of complement as well as speculation on the structural changes of antibody-antigen complexes is presented. PMID:13620844

Interpretation of the Lempel-Ziv complexity measure in the context of biomedical signal analysis.

PubMed

Aboy, Mateo; Hornero, Roberto; Abásolo, Daniel; Alvarez, Daniel

2006-11-01

Lempel-Ziv complexity (LZ) and derived LZ algorithms have been extensively used to solve information theoretic problems such as coding and lossless data compression. In recent years, LZ has been widely used in biomedical applications to estimate the complexity of discrete-time signals. Despite its popularity as a complexity measure for biosignal analysis, the question of LZ interpretability and its relationship to other signal parameters and to other metrics has not been previously addressed. We have carried out an investigation aimed at gaining a better understanding of the LZ complexity itself, especially regarding its interpretability as a biomedical signal analysis technique. Our results indicate that LZ is particularly useful as a scalar metric to estimate the bandwidth of random processes and the harmonic variability in quasi-periodic signals.

Cohesin Can Remain Associated with Chromosomes during DNA Replication.

PubMed

Rhodes, James D P; Haarhuis, Judith H I; Grimm, Jonathan B; Rowland, Benjamin D; Lavis, Luke D; Nasmyth, Kim A

2017-09-19

To ensure disjunction to opposite poles during anaphase, sister chromatids must be held together following DNA replication. This is mediated by cohesin, which is thought to entrap sister DNAs inside a tripartite ring composed of its Smc and kleisin (Scc1) subunits. How such structures are created during S phase is poorly understood, in particular whether they are derived from complexes that had entrapped DNAs prior to replication. To address this, we used selective photobleaching to determine whether cohesin associated with chromatin in G1 persists in situ after replication. We developed a non-fluorescent HaloTag ligand to discriminate the fluorescence recovery signal from labeling of newly synthesized Halo-tagged Scc1 protein (pulse-chase or pcFRAP). In cells where cohesin turnover is inactivated by deletion of WAPL, Scc1 can remain associated with chromatin throughout S phase. These findings suggest that cohesion might be generated by cohesin that is already bound to un-replicated DNA. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Small organelle, big responsibility: the role of centrosomes in development and disease

PubMed Central

Chavali, Pavithra L.; Pütz, Monika; Gergely, Fanni

2014-01-01

The centrosome, a key microtubule organizing centre, is composed of centrioles, embedded in a protein-rich matrix. Centrosomes control the internal spatial organization of somatic cells, and as such contribute to cell division, cell polarity and migration. Upon exiting the cell cycle, most cell types in the human body convert their centrioles into basal bodies, which drive the assembly of primary cilia, involved in sensing and signal transduction at the cell surface. Centrosomal genes are targeted by mutations in numerous human developmental disorders, ranging from diseases exclusively affecting brain development, through global growth failure syndromes to diverse pathologies associated with ciliary malfunction. Despite our much-improved understanding of centrosome function in cellular processes, we know remarkably little of its role in the organismal context, especially in mammals. In this review, we examine how centrosome dysfunction impacts on complex physiological processes and speculate on the challenges we face when applying knowledge generated from in vitro and in vivo model systems to human development. PMID:25047622

Nucleoporin MOS7/Nup88 contributes to plant immunity and nuclear accumulation of defense regulators.

PubMed

Wiermer, Marcel; Germain, Hugo; Cheng, Yu Ti; García, Ana V; Parker, Jane E; Li, Xin

2010-01-01

Controlled nucleocytoplasmic trafficking is an important feature for fine-tuning signaling pathways in eukaryotic organisms. Nuclear pore complexes (NPCs) composed of nucleoporin proteins (Nups) are essential for the exchange of macromolecules across the nuclear envelope. A recent genetic screen in our laboratory identified a partial loss-of-function mutation in Arabidopsis MOS7/Nup88 that causes defects in basal immunity, Resistance (R) protein-mediated defense and systemic acquired resistance. In Drosophila and mammalian cells, exportin-mediated nuclear export of activated Rel/NFκB transcription factors is enhanced in nup88 mutants resulting in immune response failure. Consistent with Nup88 promoting nuclear retention of NFκB, our functional analyses revealed that MOS7/Nup88 is required for appropriate nuclear accumulation of the autoactivated R protein snc1, as well as the key immune regulators EDS1 and NPR1. These results suggest that controlling the nuclear concentrations of specific immune regulators is fundamental for defining defense outputs.

Evidence for the involvement of the anthranilate degradation pathway in Pseudomonas aeruginosa biofilm formation

PubMed Central

Costaglioli, Patricia; Barthe, Christophe; Claverol, Stephane; Brözel, Volker S; Perrot, Michel; Crouzet, Marc; Bonneu, Marc; Garbay, Bertrand; Vilain, Sebastien

2012-01-01

Bacterial biofilms are complex cell communities found attached to surfaces and surrounded by an extracellular matrix composed of exopolysaccharides, DNA, and proteins. We investigated the whole-genome expression profile of Pseudomonas aeruginosa sessile cells (SCs) present in biofilms developed on a glass wool substratum. The transcriptome and proteome of SCs were compared with those of planktonic cell cultures. Principal component analysis revealed a biofilm-specific gene expression profile. Our study highlighted the overexpression of genes controlling the anthranilate degradation pathway in the SCs grown on glass wool for 24 h. In this condition, the metabolic pathway that uses anthranilate for Pseudomonas quinolone signal production was not activated, which suggested that anthranilate was primarily being consumed for energy metabolism. Transposon mutants defective for anthranilate degradation were analyzed in a simple assay of biofilm formation. The phenotypic analyses confirmed that P. aeruginosa biofilm formation partially depended on the activity of the anthranilate degradation pathway. This work points to a new feature concerning anthranilate metabolism in P. aeruginosa SCs. PMID:23170231

Browsing the Real World using Organic Electronics, Si-Chips, and a Human Touch.

PubMed

Berggren, Magnus; Simon, Daniel T; Nilsson, David; Dyreklev, Peter; Norberg, Petronella; Nordlinder, Staffan; Ersman, Peter Andersson; Gustafsson, Göran; Wikner, J Jacob; Hederén, Jan; Hentzell, Hans

2016-03-09

Organic electronics have been developed according to an orthodox doctrine advocating "all-printed'', "all-organic'' and "ultra-low-cost'' primarily targeting various e-paper applications. In order to harvest from the great opportunities afforded with organic electronics potentially operating as communication and sensor outposts within existing and future complex communication infrastructures, high-quality computing and communication protocols must be integrated with the organic electronics. Here, we debate and scrutinize the twinning of the signal-processing capability of traditional integrated silicon chips with organic electronics and sensors, and to use our body as a natural local network with our bare hand as the browser of the physical world. The resulting platform provides a body network, i.e., a personalized web, composed of e-label sensors, bioelectronics, and mobile devices that together make it possible to monitor and record both our ambience and health-status parameters, supported by the ubiquitous mobile network and the resources of the "cloud". © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Interaction of bombesin and its fragments with gold nanoparticles analyzed using surface-enhanced Raman spectroscopy

NASA Astrophysics Data System (ADS)

Tąta, Agnieszka; Szkudlarek, Aleksandra; Kim, Younkyoo; Proniewicz, Edyta

2017-02-01

This work demonstrates the application of commercially available stable surface composed of gold nanograins with diameters ranging from 70 to 226 nm deposited onto silicon wafer for surface-enhanced Raman scattering investigations of biologically active compounds, such as bombesin (BN) and its fragments. BN is an important neurotransmitter involved in a complex signaling pathways and biological responses; for instance, hypertensive action, contractive on uterus, colon or ileum, locomotor activity, stimulation of gastric and insulin secretion as well as growth promotion of various tumor cell lines, including: lung, prostate, stomach, colon, and breast. It has also been shown that 8-14 BN C-terminal fragment partially retains the biological activity of BN. The SERS results for BN and its fragment demonstrated that (1) three amino acids from these peptides sequence; i.e., L-histidine, L-methionine, and L-tryptophan, are involved in the interaction with gold coated silicon wafer and (2) the strength of these interactions depends upon the aforementioned amino acids position in the peptide sequence.

A network of networks model to study phase synchronization using structural connection matrix of human brain

NASA Astrophysics Data System (ADS)

Ferrari, F. A. S.; Viana, R. L.; Reis, A. S.; Iarosz, K. C.; Caldas, I. L.; Batista, A. M.

2018-04-01

The cerebral cortex plays a key role in complex cortical functions. It can be divided into areas according to their function (motor, sensory and association areas). In this paper, the cerebral cortex is described as a network of networks (cortex network), we consider that each cortical area is composed of a network with small-world property (cortical network). The neurons are assumed to have bursting properties with the dynamics described by the Rulkov model. We study the phase synchronization of the cortex network and the cortical networks. In our simulations, we verify that synchronization in cortex network is not homogeneous. Besides, we focus on the suppression of neural phase synchronization. Synchronization can be related to undesired and pathological abnormal rhythms in the brain. For this reason, we consider the delayed feedback control to suppress the synchronization. We show that delayed feedback control is efficient to suppress synchronous behavior in our network model when an appropriate signal intensity and time delay are defined.

Joint analysis of multiple high-dimensional data types using sparse matrix approximations of rank-1 with applications to ovarian and liver cancer.

PubMed

Okimoto, Gordon; Zeinalzadeh, Ashkan; Wenska, Tom; Loomis, Michael; Nation, James B; Fabre, Tiphaine; Tiirikainen, Maarit; Hernandez, Brenda; Chan, Owen; Wong, Linda; Kwee, Sandi

2016-01-01

Technological advances enable the cost-effective acquisition of Multi-Modal Data Sets (MMDS) composed of measurements for multiple, high-dimensional data types obtained from a common set of bio-samples. The joint analysis of the data matrices associated with the different data types of a MMDS should provide a more focused view of the biology underlying complex diseases such as cancer that would not be apparent from the analysis of a single data type alone. As multi-modal data rapidly accumulate in research laboratories and public databases such as The Cancer Genome Atlas (TCGA), the translation of such data into clinically actionable knowledge has been slowed by the lack of computational tools capable of analyzing MMDSs. Here, we describe the Joint Analysis of Many Matrices by ITeration (JAMMIT) algorithm that jointly analyzes the data matrices of a MMDS using sparse matrix approximations of rank-1. The JAMMIT algorithm jointly approximates an arbitrary number of data matrices by rank-1 outer-products composed of "sparse" left-singular vectors (eigen-arrays) that are unique to each matrix and a right-singular vector (eigen-signal) that is common to all the matrices. The non-zero coefficients of the eigen-arrays identify small subsets of variables for each data type (i.e., signatures) that in aggregate, or individually, best explain a dominant eigen-signal defined on the columns of the data matrices. The approximation is specified by a single "sparsity" parameter that is selected based on false discovery rate estimated by permutation testing. Multiple signals of interest in a given MDDS are sequentially detected and modeled by iterating JAMMIT on "residual" data matrices that result from a given sparse approximation. We show that JAMMIT outperforms other joint analysis algorithms in the detection of multiple signatures embedded in simulated MDDS. On real multimodal data for ovarian and liver cancer we show that JAMMIT identified multi-modal signatures that were clinically informative and enriched for cancer-related biology. Sparse matrix approximations of rank-1 provide a simple yet effective means of jointly reducing multiple, big data types to a small subset of variables that characterize important clinical and/or biological attributes of the bio-samples from which the data were acquired.

Utilization of Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS) to Identify environmental Strains of Mycobacterium Complex

EPA Science Inventory

Species within the Mycobacterium avium Complex (MAC) group are found to be both prevalent and persistent in drinking water distribution systems. The MAC is composed of two predominant species: M. avium and M. intracellulare. These species have the ability to survive drinking ...

HOW to Recognize and Control Sooty Molds

Treesearch

Kenneth J. Jr. Kessler

1992-01-01

Sooty molds are dark fungi that grow on honeydew excreted by sucking insects or on exudates from leaves of certain plants. Typically, sooty mold growths are composed of fungal complexes made up of ascomycetes and fungi imperfecti. Some of the common genera of fungi found in sooty mold complexes are Cladosporium, Aureobasidium, Antennariella, Limacinula, Scorias, and...

Modular modelling with Physiome standards

PubMed Central

Nickerson, David P.; Nielsen, Poul M. F.; Hunter, Peter J.

2016-01-01

Key points The complexity of computational models is increasing, supported by research in modelling tools and frameworks. But relatively little thought has gone into design principles for complex models.We propose a set of design principles for complex model construction with the Physiome standard modelling protocol CellML.By following the principles, models are generated that are extensible and are themselves suitable for reuse in larger models of increasing complexity.We illustrate these principles with examples including an architectural prototype linking, for the first time, electrophysiology, thermodynamically compliant metabolism, signal transduction, gene regulation and synthetic biology.The design principles complement other Physiome research projects, facilitating the application of virtual experiment protocols and model analysis techniques to assist the modelling community in creating libraries of composable, characterised and simulatable quantitative descriptions of physiology. Abstract The ability to produce and customise complex computational models has great potential to have a positive impact on human health. As the field develops towards whole‐cell models and linking such models in multi‐scale frameworks to encompass tissue, organ, or organism levels, reuse of previous modelling efforts will become increasingly necessary. Any modelling group wishing to reuse existing computational models as modules for their own work faces many challenges in the context of construction, storage, retrieval, documentation and analysis of such modules. Physiome standards, frameworks and tools seek to address several of these challenges, especially for models expressed in the modular protocol CellML. Aside from providing a general ability to produce modules, there has been relatively little research work on architectural principles of CellML models that will enable reuse at larger scales. To complement and support the existing tools and frameworks, we develop a set of principles to address this consideration. The principles are illustrated with examples that couple electrophysiology, signalling, metabolism, gene regulation and synthetic biology, together forming an architectural prototype for whole‐cell modelling (including human intervention) in CellML. Such models illustrate how testable units of quantitative biophysical simulation can be constructed. Finally, future relationships between modular models so constructed and Physiome frameworks and tools are discussed, with particular reference to how such frameworks and tools can in turn be extended to complement and gain more benefit from the results of applying the principles. PMID:27353233

The FANCJ/MutLα interaction is required for correction of the cross-link response in FA-J cells

PubMed Central

Peng, Min; Litman, Rachel; Xie, Jenny; Sharma, Sudha; Brosh, Robert M; Cantor, Sharon B

2007-01-01

FANCJ also called BACH1/BRIP1 was first linked to hereditary breast cancer through its direct interaction with BRCA1. FANCJ was also recently identified as a Fanconi anemia (FA) gene product, establishing FANCJ as an essential tumor suppressor. Similar to other FA cells, FANCJ-null (FA-J) cells accumulate 4N DNA content in response to DNA interstrand crosslinks (ICLs). This accumulation is corrected by reintroduction of wild-type FANCJ. Here, we show that FANCJ interacts with the mismatch repair complex MutLα, composed of PMS2 and MLH1. Specifically, FANCJ directly interacts with MLH1 independent of BRCA1, through its helicase domain. Genetic studies reveal that FANCJ helicase activity and MLH1 binding, but not BRCA1 binding, are essential to correct the FA-J cells' ICL-induced 4N DNA accumulation and sensitivity to ICLs. These results suggest that the FANCJ/MutLα interaction, but not FANCJ/BRCA1 interaction, is essential for establishment of a normal ICL-induced response. The functional role of the FANCJ/MutLα complex demonstrates a novel link between FA and MMR, and predicts a broader role for FANCJ in DNA damage signaling independent of BRCA1. PMID:17581638

Pulmonary immunity and extracellular matrix interactions.

PubMed

O'Dwyer, David N; Gurczynski, Stephen J; Moore, Bethany B

2018-04-09

The lung harbors a complex immune system composed of both innate and adaptive immune cells. Recognition of infection and injury by receptors on lung innate immune cells is crucial for generation of antigen-specific responses by adaptive immune cells. The extracellular matrix of the lung, comprising the interstitium and basement membrane, plays a key role in the regulation of these immune systems. The matrix consists of several hundred assembled proteins that interact to form a bioactive scaffold. This template, modified by enzymes, acts to facilitate cell function and differentiation and changes dynamically with age and lung disease. Herein, we explore relationships between innate and adaptive immunity and the lung extracellular matrix. We discuss the interactions between extracellular matrix proteins, including glycosaminoglycans, with prominent effects on innate immune signaling effectors such as toll-like receptors. We describe the relationship of extracellular matrix proteins with adaptive immunity and leukocyte migration to sites of injury within the lung. Further study of these interactions will lead to greater knowledge of the role of matrix biology in lung immunity. The development of novel therapies for acute and chronic lung disease is dependent on a comprehensive understanding of these complex matrix-immunity interactions. Copyright © 2017 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

Characterization of C-ring component assembly in flagellar motors from amino acid coevolution

PubMed Central

dos Santos, Ricardo Nascimento; Khan, Shahid

2018-01-01

Bacterial flagellar motility, an important virulence factor, is energized by a rotary motor localized within the flagellar basal body. The rotor module consists of a large framework (the C-ring), composed of the FliG, FliM and FliN proteins. FliN and FliM contacts the FliG torque ring to control the direction of flagellar rotation. We report that structure-based models constrained only by residue coevolution can recover the binding interface of atomic X-ray dimer complexes with remarkable accuracy (approx. 1 Å RMSD). We propose a model for FliM–FliN heterodimerization, which agrees accurately with homologous interfaces as well as in situ cross-linking experiments, and hence supports a proposed architecture for the lower portion of the C-ring. Furthermore, this approach allowed the identification of two discrete and interchangeable homodimerization interfaces between FliM middle domains that agree with experimental measurements and might be associated with C-ring directional switching dynamics triggered upon binding of CheY signal protein. Our findings provide structural details of complex formation at the C-ring that have been difficult to obtain with previous methodologies and clarify the architectural principle that underpins the ultra-sensitive allostery exhibited by this ring assembly that controls the clockwise or counterclockwise rotation of flagella. PMID:29892378

Multi-channel non-invasive fetal electrocardiography detection using wavelet decomposition

NASA Astrophysics Data System (ADS)

Almeida, Javier; Ruano, Josué; Corredor, Germán.; Romo-Bucheli, David; Navarro-Vargas, José Ricardo; Romero, Eduardo

2017-11-01

Non-invasive fetal electrocardiography (fECG) has attracted the medical community because of the importance of fetal monitoring. However, its implementation in clinical practice is challenging: the fetal signal has a low Signal- to-Noise-Ratio and several signal sources are present in the maternal abdominal electrocardiography (AECG). This paper presents a novel method to detect the fetal signal from a multi-channel maternal AECG. The method begins by applying filters and signal detrending the AECG signals. Afterwards, the maternal QRS complexes are identified and subtracted. The residual signals are used to detect the fetal QRS complex. Intervals of these signals are analyzed by using a wavelet decomposition. The resulting representation feds a previously trained Random Forest (RF) classifier that identifies signal intervals associated to fetal QRS complex. The method was evaluated on a public available dataset: the Physionet2013 challenge. A set of 50 maternal AECG records were used to train the RF classifier. The evaluation was carried out in signals intervals extracted from additional 25 maternal AECG. The proposed method yielded an 83:77% accuracy in the fetal QRS complex classification task.

Structural characterization of the Yersinia pestis type III secretion system needle protein YscF in complex with its heterodimeric chaperone YscE/YscG

PubMed Central

Sun, Ping; Tropea, Joseph E.; Austin, Brian P.; Cherry, Scott; Waugh, David S.

2008-01-01

Summary The plague-causing bacterium Yersinia pestis utilizes a Type III Secretion System (T3SS) to deliver effector proteins into mammalian cells where they interfere with signal transduction pathways that mediate phagocytosis and the inflammatory response. Effector proteins are injected through a hollow needle structure composed of the protein YscF. YscG and YscE act as "chaperones" to prevent premature polymerization of YscF in the cytosol of the bacterium prior to assembly of the needle. Here, we report the crystal structure of the YscEFG protein complex at 1.8 Å resolution. Overall, the structure is similar to that of the analogous PscEFG complex from the Pseudomonas aeruginosa T3SS, but there are noteworthy differences. The structure confirms that, like PscG, YscG is a member of the tetratricopeptide repeat (TPR) family of proteins. YscG binds tightly to the C-terminal half of YscF, implying that it is this region of YscF that controls its polymerization into the needle structure. YscE interacts with the N-terminal TPR motif of YscG but makes very little direct contact with YscF. Its function may be to stabilize the structure of YscG and/or to participate in recruiting the complex to the secretion apparatus. No electron density could be observed for the N-terminal 49 residues of YscF. This and additional evidence suggest that the N-terminus of YscF is disordered in the complex with YscE and YscG. As expected, conserved residues in the C-terminal half of YscF mediate important intra- and intermolecular interactions in the complex. Moreover, the phenotypes of some previously characterized mutations in the C-terminal half of YscF can be rationalized in terms of the structure of the heterotrimeric YscEFG complex. PMID:18281060

Structural Characterization of the Yersinia pestis Type III Secretion System Needle Protein YscF in Complex with Its Heterodimeric Chaperone YscE/YscG

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Ping; Tropea, Joseph E.; Austin, Brian P.

2008-05-03

The plague-causing bacterium Yersinia pestis utilizes a type III secretion system to deliver effector proteins into mammalian cells where they interfere with signal transduction pathways that mediate phagocytosis and the inflammatory response. Effector proteins are injected through a hollow needle structure composed of the protein YscF. YscG and YscE act as 'chaperones' to prevent premature polymerization of YscF in the cytosol of the bacterium prior to assembly of the needle. Here, we report the crystal structure of the YscEFG protein complex at 1.8 {angstrom} resolution. Overall, the structure is similar to that of the analogous PscEFG complex from the Pseudomonasmore » aeruginosa type III secretion system, but there are noteworthy differences. The structure confirms that, like PscG, YscG is a member of the tetratricopeptide repeat family of proteins. YscG binds tightly to the C-terminal half of YscF, implying that it is this region of YscF that controls its polymerization into the needle structure. YscE interacts with the N-terminal tetratricopeptide repeat motif of YscG but makes very little direct contact with YscF. Its function may be to stabilize the structure of YscG and/or to participate in recruiting the complex to the secretion apparatus. No electron density could be observed for the 49 N-terminal residues of YscF. This and additional evidence suggest that the N-terminus of YscF is disordered in the complex with YscE and YscG. As expected, conserved residues in the C-terminal half of YscF mediate important intra- and intermolecular interactions in the complex. Moreover, the phenotypes of some previously characterized mutations in the C-terminal half of YscF can be rationalized in terms of the structure of the heterotrimeric YscEFG complex.« less

Uniqueness and characterization theorems for generalized entropies

NASA Astrophysics Data System (ADS)

Enciso, Alberto; Tempesta, Piergiulio

2017-12-01

The requirement that an entropy function be composable is key: it means that the entropy of a compound system can be calculated in terms of the entropy of its independent components. We prove that, under mild regularity assumptions, the only composable generalized entropy in trace form is the Tsallis one-parameter family (which contains Boltzmann-Gibbs as a particular case). This result leads to the use of generalized entropies that are not of trace form, such as Rényi’s entropy, in the study of complex systems. In this direction, we also present a characterization theorem for a large class of composable non-trace-form entropy functions with features akin to those of Rényi’s entropy.

Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Su-Chang; Lo, Yu-Chih; Wu, Hao

2010-08-23

MyD88, IRAK4 and IRAK2 are critical signalling mediators of the TLR/IL1-R superfamily. Here we report the crystal structure of the MyD88-IRAK4-IRAK2 death domain (DD) complex, which surprisingly reveals a left-handed helical oligomer that consists of 6 MyD88, 4 IRAK4 and 4 IRAK2 DDs. Assembly of this helical signalling tower is hierarchical, in which MyD88 recruits IRAK4 and the MyD88-IRAK4 complex recruits the IRAK4 substrates IRAK2 or the related IRAK1. Formation of these Myddosome complexes brings the kinase domains of IRAKs into proximity for phosphorylation and activation. Composite binding sites are required for recruitment of the individual DDs in the complex,more » which are confirmed by mutagenesis and previously identified signalling mutations. Specificities in Myddosome formation are dictated by both molecular complementarity and correspondence of surface electrostatics. The MyD88-IRAK4-IRAK2 complex provides a template for Toll signalling in Drosophila and an elegant mechanism for versatile assembly and regulation of DD complexes in signal transduction.« less

A deep learning approach for fetal QRS complex detection.

PubMed

Zhong, Wei; Liao, Lijuan; Guo, Xuemei; Wang, Guoli

2018-04-20

Non-invasive foetal electrocardiography (NI-FECG) has the potential to provide more additional clinical information for detecting and diagnosing fetal diseases. We propose and demonstrate a deep learning approach for fetal QRS complex detection from raw NI-FECG signals by using a convolutional neural network (CNN) model. The main objective is to investigate whether reliable fetal QRS complex detection performance can still be obtained from features of single-channel NI-FECG signals, without canceling maternal ECG (MECG) signals. A deep learning method is proposed for recognizing fetal QRS complexes. Firstly, we collect data from set-a of the PhysioNet/computing in Cardiology Challenge database. The sample entropy method is used for signal quality assessment. Part of the bad quality signals is excluded in the further analysis. Secondly, in the proposed method, the features of raw NI-FECG signals are normalized before they are fed to a CNN classifier to perform fetal QRS complex detection. We use precision, recall, F-measure and accuracy as the evaluation metrics to assess the performance of fetal QRS complex detection. The proposed deep learning method can achieve relatively high precision (75.33%), recall (80.54%), and F-measure scores (77.85%) compared with three other well-known pattern classification methods, namely KNN, naive Bayes and SVM. the proposed deep learning method can attain reliable fetal QRS complex detection performance from the raw NI-FECG signals without canceling MECG signals. In addition, the influence of different activation functions and signal quality assessment on classification performance are evaluated, and results show that Relu outperforms the Sigmoid and Tanh on this particular task, and better classification performance is obtained with the signal quality assessment step in this study.

Resonant spatiotemporal learning in large random recurrent networks.

PubMed

Daucé, Emmanuel; Quoy, Mathias; Doyon, Bernard

2002-09-01

Taking a global analogy with the structure of perceptual biological systems, we present a system composed of two layers of real-valued sigmoidal neurons. The primary layer receives stimulating spatiotemporal signals, and the secondary layer is a fully connected random recurrent network. This secondary layer spontaneously displays complex chaotic dynamics. All connections have a constant time delay. We use for our experiments a Hebbian (covariance) learning rule. This rule slowly modifies the weights under the influence of a periodic stimulus. The effect of learning is twofold: (i) it simplifies the secondary-layer dynamics, which eventually stabilizes to a periodic orbit; and (ii) it connects the secondary layer to the primary layer, and realizes a feedback from the secondary to the primary layer. This feedback signal is added to the incoming signal, and matches it (i.e., the secondary layer performs a one-step prediction of the forthcoming stimulus). After learning, a resonant behavior can be observed: the system resonates with familiar stimuli, which activates a feedback signal. In particular, this resonance allows the recognition and retrieval of partial signals, and dynamic maintenance of the memory of past stimuli. This resonance is highly sensitive to the temporal relationships and to the periodicity of the presented stimuli. When we present stimuli which do not match in time or space, the feedback remains silent. The number of different stimuli for which resonant behavior can be learned is analyzed. As with Hopfield networks, the capacity is proportional to the size of the second, recurrent layer. Moreover, the high capacity displayed allows the implementation of our model on real-time systems interacting with their environment. Such an implementation is reported in the case of a simple behavior-based recognition task on a mobile robot. Finally, we present some functional analogies with biological systems in terms of autonomy and dynamic binding, and present some hypotheses on the computational role of feedback connections.

A high-speed trapezoid image sensor design for continuous traffic monitoring at signalized intersection approaches.

DOT National Transportation Integrated Search

2014-10-01

The goal of this project is to monitor traffic flow continuously with an innovative camera system composed of a custom : designed image sensor integrated circuit (IC) containing trapezoid pixel array and camera system that is capable of : intelligent...

Layered intrusions of the Duluth Complex, Minnesota, USA

USGS Publications Warehouse

Miller, J.D.; Ripley, E.M.; ,

1996-01-01

The Duluth Complex and associated subvolcanic intrusions comprise a large (5000 km2) intrusive complex in northeastern Minnesota that was emplaced into comagmatic volcanics during the development of the 1.1 Ga Midcontinent rift in North America. In addition to anorthositic and felsic intrusions, the Duluth Complex is composed of many individual mafic layered intrusions of tholeiitic affinity. The cumulate stratigraphies and cryptic variations of six of the better exposed and better studied intrusions are described here to demonstrate the variability in their cumulus mineral paragenesis.

Biological network extraction from scientific literature: state of the art and challenges.

PubMed

Li, Chen; Liakata, Maria; Rebholz-Schuhmann, Dietrich

2014-09-01

Networks of molecular interactions explain complex biological processes, and all known information on molecular events is contained in a number of public repositories including the scientific literature. Metabolic and signalling pathways are often viewed separately, even though both types are composed of interactions involving proteins and other chemical entities. It is necessary to be able to combine data from all available resources to judge the functionality, complexity and completeness of any given network overall, but especially the full integration of relevant information from the scientific literature is still an ongoing and complex task. Currently, the text-mining research community is steadily moving towards processing the full body of the scientific literature by making use of rich linguistic features such as full text parsing, to extract biological interactions. The next step will be to combine these with information from scientific databases to support hypothesis generation for the discovery of new knowledge and the extension of biological networks. The generation of comprehensive networks requires technologies such as entity grounding, coordination resolution and co-reference resolution, which are not fully solved and are required to further improve the quality of results. Here, we analyse the state of the art for the extraction of network information from the scientific literature and the evaluation of extraction methods against reference corpora, discuss challenges involved and identify directions for future research. © The Author 2013. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Temporal information partitioning: Characterizing synergy, uniqueness, and redundancy in interacting environmental variables

NASA Astrophysics Data System (ADS)

Goodwell, Allison E.; Kumar, Praveen

2017-07-01

Information theoretic measures can be used to identify nonlinear interactions between source and target variables through reductions in uncertainty. In information partitioning, multivariate mutual information is decomposed into synergistic, unique, and redundant components. Synergy is information shared only when sources influence a target together, uniqueness is information only provided by one source, and redundancy is overlapping shared information from multiple sources. While this partitioning has been applied to provide insights into complex dependencies, several proposed partitioning methods overestimate redundant information and omit a component of unique information because they do not account for source dependencies. Additionally, information partitioning has only been applied to time-series data in a limited context, using basic pdf estimation techniques or a Gaussian assumption. We develop a Rescaled Redundancy measure (Rs) to solve the source dependency issue, and present Gaussian, autoregressive, and chaotic test cases to demonstrate its advantages over existing techniques in the presence of noise, various source correlations, and different types of interactions. This study constitutes the first rigorous application of information partitioning to environmental time-series data, and addresses how noise, pdf estimation technique, or source dependencies can influence detected measures. We illustrate how our techniques can unravel the complex nature of forcing and feedback within an ecohydrologic system with an application to 1 min environmental signals of air temperature, relative humidity, and windspeed. The methods presented here are applicable to the study of a broad range of complex systems composed of interacting variables.

Enhanced Vibrational Echo Correlation Spectrometer for the Study of Molecular Dynamics, Structures, and Analytical Applications

DTIC Science & Technology

2006-09-10

ultrafast IR 2D vibrational echo spectrometer. The major improvement involved a new dual MCT array detector composed of two 32 x 1 element MCT IR... detector arrays. The dual array makes it possible to improve signal- to- noise ratio in the heterodyne detection of the vibrational echo signal. To...are dispersed in a monochromator and then detected with the new 2x32-element MCT IR array detector . As discussed above, the function of the local

The Role of Protein Elongation Factor eEF1A2 in Breast Cancer

DTIC Science & Technology

2006-09-01

serve as regulators of multiple signaling pathways (15-18). PIs are composed of an inositol ring covalently bound to a lipid phosphatidic acid ...mouse model of aristolochic acid nephropathy, and human kidney-proximal tubule cells. Satisfyingly, one of these targets is Dishevelled 2 (DVL2...Rho signaling proteins together. The two human eEF1A isoforms (eEF1A2 and eEF1A2) are very similar proteins (92% amino acid identity). The two

Computer model of a reverberant and parallel circuit coupling

NASA Astrophysics Data System (ADS)

Kalil, Camila de Andrade; de Castro, Maria Clícia Stelling; Cortez, Célia Martins

2017-11-01

The objective of the present study was to deepen the knowledge about the functioning of the neural circuits by implementing a signal transmission model using the Graph Theory in a small network of neurons composed of an interconnected reverberant and parallel circuit, in order to investigate the processing of the signals in each of them and the effects on the output of the network. For this, a program was developed in C language and simulations were done using neurophysiological data obtained in the literature.

Honeybees Learn Odour Mixtures via a Selection of Key Odorants

PubMed Central

Reinhard, Judith; Sinclair, Michael; Srinivasan, Mandyam V.; Claudianos, Charles

2010-01-01

Background The honeybee has to detect, process and learn numerous complex odours from her natural environment on a daily basis. Most of these odours are floral scents, which are mixtures of dozens of different odorants. To date, it is still unclear how the bee brain unravels the complex information contained in scent mixtures. Methodology/Principal Findings This study investigates learning of complex odour mixtures in honeybees using a simple olfactory conditioning procedure, the Proboscis-Extension-Reflex (PER) paradigm. Restrained honeybees were trained to three scent mixtures composed of 14 floral odorants each, and then tested with the individual odorants of each mixture. Bees did not respond to all odorants of a mixture equally: They responded well to a selection of key odorants, which were unique for each of the three scent mixtures. Bees showed less or very little response to the other odorants of the mixtures. The bees' response to mixtures composed of only the key odorants was as good as to the original mixtures of 14 odorants. A mixture composed of the other, non-key-odorants elicited a significantly lower response. Neither an odorant's volatility or molecular structure, nor learning efficiencies for individual odorants affected whether an odorant became a key odorant for a particular mixture. Odorant concentration had a positive effect, with odorants at high concentration likely to become key odorants. Conclusions/Significance Our study suggests that the brain processes complex scent mixtures by predominantly learning information from selected key odorants. Our observations on key odorant learning lend significant support to previous work on olfactory learning and mixture processing in honeybees. PMID:20161714

Purification and characterization of a cellulolytic multienzyme complex produced by Neocallimastix patriciarum J11.

PubMed

Wang, Hui-Chang; Chen, Yo-Chia; Hseu, Ruey-Shyang

2014-08-22

Understanding the roles of the components of the multienzyme complex of the anaerobial cellulase system, acting on complex substrates, is crucial to the development of efficient cellulase systems for industrial applications such as converting lignocellulose to sugars for bioethanol production. In this study, we purified the multienzyme complex of Neocallimastix patriciarum J11 from a broth through cellulose affinity purification. The multienzyme complex is composed of at least 12 comprised proteins, based on sodium dodecyl sulfate polyacrylamide gel electrophoresis. Eight of these constituents have demonstrated β-glucanase activity on zymogram analysis. The multienzyme complex contained scaffoldings that respond to the gathering of the cellulolytic components. The levels and subunit ratio of the multienzyme complex from N. patriciarum J11 might have been affected by their utilized carbon sources, whereas the components of the complexes were consistent. The trypsin-digested peptides of six proteins were matched to the sequences of cellulases originating from rumen fungi, based on identification through liquid chromatography/mass spectrometry, revealing that at least three types of cellulase, including one endoglucanase and two exoglucanases, could be found in the multienzyme complex of N. patriciarum J11. The cellulolytic subunits could hydrolyze synergistically on both the internal bonds and the reducing and nonreducing ends of cellulose. Based on our research, our findings are the first to depict the composition of the multienzyme complex produced by N. patriciarum J11, and this complex is composed of scaffoldin and three types of cellulase. Copyright © 2014 Elsevier Inc. All rights reserved.

Singular spectrum and singular entropy used in signal processing of NC table

NASA Astrophysics Data System (ADS)

Wang, Linhong; He, Yiwen

2011-12-01

NC (numerical control) table is a complex dynamic system. The dynamic characteristics caused by backlash, friction and elastic deformation among each component are so complex that they have become the bottleneck of enhancing the positioning accuracy, tracking accuracy and dynamic behavior of NC table. This paper collects vibration acceleration signals from NC table, analyzes the signals with SVD (singular value decomposition) method, acquires the singular spectrum and calculates the singular entropy of the signals. The signal characteristics and their regulations of NC table are revealed via the characteristic quantities such as singular spectrum, singular entropy etc. The steep degrees of singular spectrums can be used to discriminate complex degrees of signals. The results show that the signals in direction of driving axes are the simplest and the signals in perpendicular direction are the most complex. The singular entropy values can be used to study the indetermination of signals. The results show that the signals of NC table are not simple signal nor white noise, the entropy values in direction of driving axe are lower, the entropy values increase along with the increment of driving speed and the entropy values at the abnormal working conditions such as resonance or creeping etc decrease obviously.

Complex-formation between reduced xanthine oxidase and purine substrates demonstrated by electron paramagnetic resonance

PubMed Central

Pick, Frances M.; Bray, R. C.

1969-01-01

The origin of the Rapid molybdenum electron-paramagnetic-resonance signals, which are obtained on reducing xanthine oxidase with purine or with xanthine, and whose parameters were measured by Bray & Vänngård (1969), was studied. It is concluded that these signals represent complexes of reduced enzyme with substrate molecules. Xanthine forms one complex at high concentrations and a different one at low concentrations. Purine forms a complex indistinguishable from the low-concentration xanthine complex. There are indications that some other substrates also form complexes, but uric acid, a reaction product, does not appear to do so. The possible significance of the complexes in the catalytic cycle of the enzyme is discussed and it is suggested that they represent substrate molecules bound at the reduced active site, waiting their turn to react there, when the enzyme has been reoxidized. Support for this role for the complexes was deduced from experiments in which frozen samples of enzyme–xanthine mixtures, prepared by the rapid-freezing method, were warmed until the signals began to change. Under these conditions an increase in amplitude of the Very Rapid signal took place. Data bearing on the origin of the Slow molybdenum signal are also discussed. This signal disappears only slowly in the presence of oxygen, and its appearance rate is unaffected by change in the concentration of dithionite. It is concluded that, like other signals from the enzyme, it is due to Mov but that a slow change of ligand takes place before it is seen. The Slow species, like the Rapid, seems capable of forming complexes with purines. PMID:4310056

Petrology, geochemistry and geochonology of the Jacupiranga ultramafic, alkaline and carbonatitic complex (southern Brazil)

NASA Astrophysics Data System (ADS)

Chmyz, Luanna; Arnaud, Nicolas; Biondi, João Carlos

2015-04-01

Brazilian carbonatitic complexes are located at the edges of the Paleozoic basins and are usually associated to tectonic crustal flexuring or deep fault zones. The Jacupiranga Complex is a 65 km² ultrabasic-alkaline carbonatitic intrusive body outcroping at the northeastern border of the Paraná Basin, South of São Paulo State (Brazil). The northern portion of the unit is mostly composed of peridotitic rocks, while the southern part contains ijolites, melteigites, clinopyroxenites and carbonatites which host a phosphate deposit, mined since 1966. Even though the carbonatites only represent 1% of the Complex's area, they have concentrated most of the historical petrogenetic studies, leaving almost unknown the petrogenetic and the geochronological characteristics of other rocks. This explains why the few petrogenetic models from the literature are very partial and mostly unsatisfactory. While the peridotitic rocks are largely hindered by the absence of fresh outcrops, the regolith thickness and the high serpentinization degree, field observations and petrographic data notably show a heterogeneous zone around the peridotitic body. That zone is composed of a large variety of lithotypes over a relatively small area (~9 km²), comprising diorites, monzodiorites, alkali feldspar syenites, trachytes, lamprophyres and syenites. Moreover, these rocks present a restricted lateral continuity (decametric) and a lack of the magmatic bedding characteristic of the ijolitic and clinopyroxenitc rocks. The southern clinopyroxenitic zone (~20 km²) is composed of clinopyroxenite and melteigite with prominent magmatic layering, probably of cumulative origin, and a body of carbonatites which outcrops over less than 1 km2 essentially composed of sovite and beforsite, with abundant apatite. The Jacupiranga Complex characteristics indicate that its formation possibly comprises at least five magmatic events which cannot at present be surely ordinated in time: a) the emplacement of the peridotitic unit; b) the intrusion and probable differentiation of the clinopyroxenites and ijolitic rocks; c) intrusions of several lithotypes forming the heterogeneous zone; d) intrusion of lamprophyric dykes into the syenites; e) the carbonatite intrusion. The precise geochronological sequence is still unknown, since only the syenites (134.9 ± 0.65 Ma this study), the carbonatite (131 Ma) and the clinopyroxenite (131 Ma) were dated at present. Our goal is now to investigate the origin and evolution of the magmas which formed the Jacupiranga Complex using geochronology with Ar/Ar, U-Pb and U-Th/He dating, as well as elemental and isotopic geochemistry. Considering that the Jacupiranga Complex is one of the most differentiated alkaline complexes around the world, this contribution will be important not only for the understanding of the unit itself but also for the general comprehension of the forming process, the evolution of the alkaline and carbonatitic magmas and the concentration of apatite in carbonatites, still controversial subjects among the scientific community.

Development of a film sensor for static and dynamic force measurement

NASA Astrophysics Data System (ADS)

Castellini, P.; Montanini, R.; Revel, G. M.

2002-09-01

In this work an innovative double-layer film sensor for the measurement of forces is presented. The sensor is a thin film (thickness below 1 mm) based on a "sandwich" structure composed of two sensing elements glued together: one layer is a capacitive film and the other is a piezoelectric film. Both the layers are sensitive to compression loads, but they are suitable for working in different frequency ranges. In fact, while the capacitive element is capable of measuring from dc up to about 400 Hz, on the contrary the piezoelectric film works in the high frequency range. The output signals of both the sensors are acquired and then filtered and processed in order to achieve a single output signal. The piezocapacitive sensor has been developed in order to synthesize, in a small and cheap device, the capability to measure compression forces in a wide range of frequencies. The sensor is very small and has many potential applications, such as in the field of modal analysis. In particular, the very small thickness allows to insert it into a composite material to measure actual loads and excitations, as well as on the surface or between different components of a more complex system in order to obtain a smart structure. This article describes the realization of the sensor and the adopted signal processing strategies. The metrological characterization procedure is discussed and results are shown for both static and dynamic calibration of the film sensor. Finally, a simple application, that highlights the benefits of the sensor, is presented.

Highly Sensitive Detection of Caspase-3/7 Activity in Living Mice Using Enzyme-Responsive 19F MRI Nanoprobes.

PubMed

Akazawa, Kazuki; Sugihara, Fuminori; Nakamura, Tatsuya; Mizukami, Shin; Kikuchi, Kazuya

2018-05-16

Highly sensitive imaging of enzymatic activities in the deep tissues of living mammals provides useful information about their biological functions and for developing new drugs; however, such imaging is challenging. 19 F magnetic resonance imaging (MRI) is suitable for noninvasive visualization of enzymatic activities without endogenous background signals. Although various enzyme-responsive 19 F MRI probes have been developed, most cannot be used for in vivo imaging because of their low sensitivity. Recently, we developed unique nanoparticles, called FLAMEs, that are composed of a liquid perfluorocarbon core and a robust silica shell, and demonstrated their outstanding sensitivity in vivo. Here, we report a highly functionalized nanoprobe, FLAME-DEVD 2, with an OFF/ON 19 F MRI switch for detecting caspase-3/7 activity based on the paramagnetic relaxation enhancement effect. To improve the cleavage efficiency of peptides by caspase-3, we designed a novel Gd 3+ complex-conjugated peptide, DEVD X ( X = 1, 2), which is a substrate peptide sequence tandemly repeated X times, and demonstrated that DEVD 2 showed faster cleavage kinetics than DEVD 1. By incorporating this novel concept into a signal activation strategy, FLAME-DEVD 2 showed a high 19 F MRI signal enhancement rate in response to caspase-3 activity. After intravenous injection of FLAME-DEVD 2 and an apoptosis-inducing reagent, caspase-3/7 activity in the spleen of a living mouse was successfully imaged by 19 F MRI. This imaging platform shows great potential for highly sensitive detection of enzymatic activities in vivo.

Neural coding of syntactic structure in learned vocalizations in the songbird.

PubMed

Fujimoto, Hisataka; Hasegawa, Taku; Watanabe, Dai

2011-07-06

Although vocal signals including human languages are composed of a finite number of acoustic elements, complex and diverse vocal patterns can be created from combinations of these elements, linked together by syntactic rules. To enable such syntactic vocal behaviors, neural systems must extract the sequence patterns from auditory information and establish syntactic rules to generate motor commands for vocal organs. However, the neural basis of syntactic processing of learned vocal signals remains largely unknown. Here we report that the basal ganglia projecting premotor neurons (HVC(X) neurons) in Bengalese finches represent syntactic rules that generate variable song sequences. When vocalizing an alternative transition segment between song elements called syllables, sparse burst spikes of HVC(X) neurons code the identity of a specific syllable type or a specific transition direction among the alternative trajectories. When vocalizing a variable repetition sequence of the same syllable, HVC(X) neurons not only signal the initiation and termination of the repetition sequence but also indicate the progress and state-of-completeness of the repetition. These different types of syntactic information are frequently integrated within the activity of single HVC(X) neurons, suggesting that syntactic attributes of the individual neurons are not programmed as a basic cellular subtype in advance but acquired in the course of vocal learning and maturation. Furthermore, some auditory-vocal mirroring type HVC(X) neurons display transition selectivity in the auditory phase, much as they do in the vocal phase, suggesting that these songbirds may extract syntactic rules from auditory experience and apply them to form their own vocal behaviors.

Generation of Long-time Complex Signals for Testing the Instruments for Detection of Voltage Quality Disturbances

NASA Astrophysics Data System (ADS)

Živanović, Dragan; Simić, Milan; Kokolanski, Zivko; Denić, Dragan; Dimcev, Vladimir

2018-04-01

Software supported procedure for generation of long-time complex test sentences, suitable for testing the instruments for detection of standard voltage quality (VQ) disturbances is presented in this paper. This solution for test signal generation includes significant improvements of computer-based signal generator presented and described in the previously published paper [1]. The generator is based on virtual instrumentation software for defining the basic signal parameters, data acquisition card NI 6343, and power amplifier for amplification of output voltage level to the nominal RMS voltage value of 230 V. Definition of basic signal parameters in LabVIEW application software is supported using Script files, which allows simple repetition of specific test signals and combination of more different test sequences in the complex composite test waveform. The basic advantage of this generator compared to the similar solutions for signal generation is the possibility for long-time test sequence generation according to predefined complex test scenarios, including various combinations of VQ disturbances defined in accordance with the European standard EN50160. Experimental verification of the presented signal generator capability is performed by testing the commercial power quality analyzer Fluke 435 Series II. In this paper are shown some characteristic complex test signals with various disturbances and logged data obtained from the tested power quality analyzer.

A Novel Fabry-Perot Cavity Fiber Sensor

NASA Astrophysics Data System (ADS)

Lin, Chun; Huang, Yuan Qing; Lei, Wang; Ye, Xiao Juan

Fabry-Perot (F-P) cavity fiber sensors are often used in acceleration, vibration and pressure measurement. When the structure of sensors are similar, there are the same disadvantages exist. A novel design of Fabry-Perot (F-P) cavity fiber sensor is described in this paper, which is composed by a non-coating end-face and a holophote. Triple beams interference is formed in the sensor and shows higher sensitivity. In order to demodulate interference signal in great background noise, two photodiodes are connected in series to form short circuit current which delimits the common mode signal. Experimental results are described for the sensor signal responding to the vibration excited by PZT.^p

Denoising embolic Doppler ultrasound signals using Dual Tree Complex Discrete Wavelet Transform.

PubMed

Serbes, Gorkem; Aydin, Nizamettin

2010-01-01

Early and accurate detection of asymptomatic emboli is important for monitoring of preventive therapy in stroke-prone patients. One of the problems in detection of emboli is the identification of an embolic signal caused by very small emboli. The amplitude of the embolic signal may be so small that advanced processing methods are required to distinguish these signals from Doppler signals arising from red blood cells. In this study instead of conventional discrete wavelet transform, the Dual Tree Complex Discrete Wavelet Transform was used for denoising embolic signals. Performances of both approaches were compared. Unlike the conventional discrete wavelet transform discrete complex wavelet transform is a shift invariant transform with limited redundancy. Results demonstrate that the Dual Tree Complex Discrete Wavelet Transform based denoising outperforms conventional discrete wavelet denoising. Approximately 8 dB improvement is obtained by using the Dual Tree Complex Discrete Wavelet Transform compared to the improvement provided by the conventional Discrete Wavelet Transform (less than 5 dB).

Are Complexity Metrics Reliable in Assessing HRV Control in Obese Patients During Sleep?

PubMed

Cabiddu, Ramona; Trimer, Renata; Borghi-Silva, Audrey; Migliorini, Matteo; Mendes, Renata G; Oliveira, Antonio D; Costa, Fernando S M; Bianchi, Anna M

2015-01-01

Obesity is associated with cardiovascular mortality. Linear methods, including time domain and frequency domain analysis, are normally applied on the heart rate variability (HRV) signal to investigate autonomic cardiovascular control, whose imbalance might promote cardiovascular disease in these patients. However, given the cardiac activity non-linearities, non-linear methods might provide better insight. HRV complexity was hereby analyzed during wakefulness and different sleep stages in healthy and obese subjects. Given the short duration of each sleep stage, complexity measures, normally extracted from long-period signals, needed be calculated on short-term signals. Sample entropy, Lempel-Ziv complexity and detrended fluctuation analysis were evaluated and results showed no significant differences among the values calculated over ten-minute signals and longer durations, confirming the reliability of such analysis when performed on short-term signals. Complexity parameters were extracted from ten-minute signal portions selected during wakefulness and different sleep stages on HRV signals obtained from eighteen obese patients and twenty controls. The obese group presented significantly reduced complexity during light and deep sleep, suggesting a deficiency in the control mechanisms integration during these sleep stages. To our knowledge, this study reports for the first time on how the HRV complexity changes in obesity during wakefulness and sleep. Further investigation is needed to quantify altered HRV impact on cardiovascular mortality in obesity.

Are Complexity Metrics Reliable in Assessing HRV Control in Obese Patients During Sleep?

PubMed Central

Cabiddu, Ramona; Trimer, Renata; Borghi-Silva, Audrey; Migliorini, Matteo; Mendes, Renata G.; Oliveira Jr., Antonio D.; Costa, Fernando S. M.; Bianchi, Anna M.

2015-01-01

Obesity is associated with cardiovascular mortality. Linear methods, including time domain and frequency domain analysis, are normally applied on the heart rate variability (HRV) signal to investigate autonomic cardiovascular control, whose imbalance might promote cardiovascular disease in these patients. However, given the cardiac activity non-linearities, non-linear methods might provide better insight. HRV complexity was hereby analyzed during wakefulness and different sleep stages in healthy and obese subjects. Given the short duration of each sleep stage, complexity measures, normally extracted from long-period signals, needed be calculated on short-term signals. Sample entropy, Lempel-Ziv complexity and detrended fluctuation analysis were evaluated and results showed no significant differences among the values calculated over ten-minute signals and longer durations, confirming the reliability of such analysis when performed on short-term signals. Complexity parameters were extracted from ten-minute signal portions selected during wakefulness and different sleep stages on HRV signals obtained from eighteen obese patients and twenty controls. The obese group presented significantly reduced complexity during light and deep sleep, suggesting a deficiency in the control mechanisms integration during these sleep stages. To our knowledge, this study reports for the first time on how the HRV complexity changes in obesity during wakefulness and sleep. Further investigation is needed to quantify altered HRV impact on cardiovascular mortality in obesity. PMID:25893856

Electronics for a prototype variable field of view PET camera using the PMT-quadrant-sharing detector array

NASA Astrophysics Data System (ADS)

Li, H.; Wong, Wai-Hoi; Zhang, N.; Wang, J.; Uribe, J.; Baghaei, H.; Yokoyama, S.

1999-06-01

Electronics for a prototype high-resolution PET camera with eight position-sensitive detector modules has been developed. Each module has 16 BGO (Bi/sub 4/Ge/sub 3/O/sub 12/) blocks (each block is composed of 49 crystals). The design goals are component and space reduction. The electronics is composed of five parts: front-end analog processing, digital position decoding, fast timing, coincidence processing and master data acquisition. The front-end analog circuit is a zone-based structure (each zone has 3/spl times/3 PMTs). Nine ADCs digitize integration signals of an active zone identified by eight trigger clusters; each cluster is composed of six photomultiplier tubes (PMTs). A trigger corresponding to a gamma ray is sent to a fast timing board to obtain a time-mark, and the nine digitized signals are passed to the position decoding board, where a real block (four PMTs) can be picked out from the zone for position decoding. Lookup tables are used for energy discrimination and to identify the gamma-hit crystal location. The coincidence board opens a 70-ns initial timing window, followed by two 20-ns true/accidental time-mark lookup table windows. The data output from the coincidence board can be acquired either in sinogram mode or in list mode with a Motorola/IRONICS VME-based system.

Instructional Specifications for Sentence Combining.

ERIC Educational Resources Information Center

Lawlor, Joseph

With particular focus on the need to provide a practical, systematic introduction to the concept of sentence combining and to the signals used to control the various combining operations, this paper provides detailed specifications for including sentence combining as part of a comprehensive plan for teaching the composing process. The…

Planning and Realization of Complex Intentions in Traumatic Brain Injury and Normal Aging

ERIC Educational Resources Information Center

Kliegel, Matthias; Eschen, Anne; Thone-Otto, Angelika I. T.

2004-01-01

The realization of delayed intentions (i.e., prospective memory) is a highly complex process composed of four phases: intention formation, retention, re-instantiation, and execution. The aim of this study was to investigate if executive functioning impairments are related to problems in the formation, re-instantiation, and execution of a delayed…

Surface monolayers of well-defined amphiphilic block copolymer composed of poly(acrylic acid) or poly(oxyethylene) and poly(styrene). Interpolymer complexation at the air-water interface

DOE Office of Scientific and Technical Information (OSTI.GOV)

Niwa, Masazo; Hayashi, Takehiro; Higashi, Nobuyuki

1990-01-01

Amphiphilic block polymers (2,3) composed of poly(acrylic acid) (PAA) or poly(oxyethylene) (POE) and chain length controlled poly(styrene) (PSt) have been prepared by using a catalytic system of tribromomethyl-terminated oligomer and manganese carbonyl. All the amphiphilic materials formed well-behaved surface monolayers, and the II-A curves for them expanded systematically with an increase of the PSt chain length.

Neural Correlates of Temporal Complexity and Synchrony during Audiovisual Correspondence Detection.

PubMed

Baumann, Oliver; Vromen, Joyce M G; Cheung, Allen; McFadyen, Jessica; Ren, Yudan; Guo, Christine C

2018-01-01

We often perceive real-life objects as multisensory cues through space and time. A key challenge for audiovisual integration is to match neural signals that not only originate from different sensory modalities but also that typically reach the observer at slightly different times. In humans, complex, unpredictable audiovisual streams lead to higher levels of perceptual coherence than predictable, rhythmic streams. In addition, perceptual coherence for complex signals seems less affected by increased asynchrony between visual and auditory modalities than for simple signals. Here, we used functional magnetic resonance imaging to determine the human neural correlates of audiovisual signals with different levels of temporal complexity and synchrony. Our study demonstrated that greater perceptual asynchrony and lower signal complexity impaired performance in an audiovisual coherence-matching task. Differences in asynchrony and complexity were also underpinned by a partially different set of brain regions. In particular, our results suggest that, while regions in the dorsolateral prefrontal cortex (DLPFC) were modulated by differences in memory load due to stimulus asynchrony, areas traditionally thought to be involved in speech production and recognition, such as the inferior frontal and superior temporal cortex, were modulated by the temporal complexity of the audiovisual signals. Our results, therefore, indicate specific processing roles for different subregions of the fronto-temporal cortex during audiovisual coherence detection.

Neural Correlates of Temporal Complexity and Synchrony during Audiovisual Correspondence Detection

PubMed Central

Ren, Yudan

2018-01-01

Abstract We often perceive real-life objects as multisensory cues through space and time. A key challenge for audiovisual integration is to match neural signals that not only originate from different sensory modalities but also that typically reach the observer at slightly different times. In humans, complex, unpredictable audiovisual streams lead to higher levels of perceptual coherence than predictable, rhythmic streams. In addition, perceptual coherence for complex signals seems less affected by increased asynchrony between visual and auditory modalities than for simple signals. Here, we used functional magnetic resonance imaging to determine the human neural correlates of audiovisual signals with different levels of temporal complexity and synchrony. Our study demonstrated that greater perceptual asynchrony and lower signal complexity impaired performance in an audiovisual coherence-matching task. Differences in asynchrony and complexity were also underpinned by a partially different set of brain regions. In particular, our results suggest that, while regions in the dorsolateral prefrontal cortex (DLPFC) were modulated by differences in memory load due to stimulus asynchrony, areas traditionally thought to be involved in speech production and recognition, such as the inferior frontal and superior temporal cortex, were modulated by the temporal complexity of the audiovisual signals. Our results, therefore, indicate specific processing roles for different subregions of the fronto-temporal cortex during audiovisual coherence detection. PMID:29354682

A large increase of sour taste receptor cells in Skn-1-deficient mice does not alter the number of their sour taste signal-transmitting gustatory neurons.

PubMed

Maeda, Naohiro; Narukawa, Masataka; Ishimaru, Yoshiro; Yamamoto, Kurumi; Misaka, Takumi; Abe, Keiko

2017-05-01

The connections between taste receptor cells (TRCs) and innervating gustatory neurons are formed in a mutually dependent manner during development. To investigate whether a change in the ratio of cell types that compose taste buds influences the number of innervating gustatory neurons, we analyzed the proportion of gustatory neurons that transmit sour taste signals in adult Skn-1a -/- mice in which the number of sour TRCs is greatly increased. We generated polycystic kidney disease 1 like 3-wheat germ agglutinin (pkd1l3-WGA)/Skn-1a +/+ and pkd1l3-WGA/Skn-1a -/- mice by crossing Skn-1a -/- mice and pkd1l3-WGA transgenic mice, in which neural pathways of sour taste signals can be visualized. The number of WGA-positive cells in the circumvallate papillae is 3-fold higher in taste buds of pkd1l3-WGA/Skn-1a -/- mice relative to pkd1l3-WGA/Skn-1a +/+ mice. Intriguingly, the ratio of WGA-positive neurons to P2X 2 -expressing gustatory neurons in nodose/petrosal ganglia was similar between pkd1l3-WGA/Skn-1a +/+ and pkd1l3-WGA/Skn-1a -/- mice. In conclusion, an alteration in the ratio of cell types that compose taste buds does not influence the number of gustatory neurons that transmit sour taste signals. Copyright © 2017. Published by Elsevier B.V.

Hydrogen exchange differences between chemoreceptor signaling complexes localize to functionally important subdomains.

PubMed

Koshy, Seena S; Li, Xuni; Eyles, Stephen J; Weis, Robert M; Thompson, Lynmarie K

2014-12-16

The goal of understanding mechanisms of transmembrane signaling, one of many key life processes mediated by membrane proteins, has motivated numerous studies of bacterial chemotaxis receptors. Ligand binding to the receptor causes a piston motion of an α helix in the periplasmic and transmembrane domains, but it is unclear how the signal is then propagated through the cytoplasmic domain to control the activity of the associated kinase CheA. Recent proposals suggest that signaling in the cytoplasmic domain involves opposing changes in dynamics in different subdomains. However, it has been difficult to measure dynamics within the functional system, consisting of extended arrays of receptor complexes with two other proteins, CheA and CheW. We have combined hydrogen exchange mass spectrometry with vesicle template assembly of functional complexes of the receptor cytoplasmic domain to reveal that there are significant signaling-associated changes in exchange, and these changes localize to key regions of the receptor involved in the excitation and adaptation responses. The methylation subdomain exhibits complex changes that include slower hydrogen exchange in complexes in a kinase-activating state, which may be partially consistent with proposals that this subdomain is stabilized in this state. The signaling subdomain exhibits significant protection from hydrogen exchange in complexes in a kinase-activating state, suggesting a tighter and/or larger interaction interface with CheA and CheW in this state. These first measurements of the stability of protein subdomains within functional signaling complexes demonstrate the promise of this approach for measuring functionally important protein dynamics within the various physiologically relevant states of multiprotein complexes.

Hydrogen Exchange Differences between Chemoreceptor Signaling Complexes Localize to Functionally Important Subdomains

PubMed Central

2015-01-01

The goal of understanding mechanisms of transmembrane signaling, one of many key life processes mediated by membrane proteins, has motivated numerous studies of bacterial chemotaxis receptors. Ligand binding to the receptor causes a piston motion of an α helix in the periplasmic and transmembrane domains, but it is unclear how the signal is then propagated through the cytoplasmic domain to control the activity of the associated kinase CheA. Recent proposals suggest that signaling in the cytoplasmic domain involves opposing changes in dynamics in different subdomains. However, it has been difficult to measure dynamics within the functional system, consisting of extended arrays of receptor complexes with two other proteins, CheA and CheW. We have combined hydrogen exchange mass spectrometry with vesicle template assembly of functional complexes of the receptor cytoplasmic domain to reveal that there are significant signaling-associated changes in exchange, and these changes localize to key regions of the receptor involved in the excitation and adaptation responses. The methylation subdomain exhibits complex changes that include slower hydrogen exchange in complexes in a kinase-activating state, which may be partially consistent with proposals that this subdomain is stabilized in this state. The signaling subdomain exhibits significant protection from hydrogen exchange in complexes in a kinase-activating state, suggesting a tighter and/or larger interaction interface with CheA and CheW in this state. These first measurements of the stability of protein subdomains within functional signaling complexes demonstrate the promise of this approach for measuring functionally important protein dynamics within the various physiologically relevant states of multiprotein complexes. PMID:25420045

Development of wireless, chipless neural stimulator by using one-port surface acoustic wave delay line and diode-capacitor interface

NASA Astrophysics Data System (ADS)

Kim, Jisung; Kim, Saehan; Lee, Keekeun

2017-06-01

For the first time, a wireless and chipless neuron stimulator was developed by utilizing a surface acoustic wave (SAW) delay line, a diode-capacitor interface, a sharp metal tip, and antennas for the stimulation of neurons in the brain. The SAW delay line supersedes presently existing complex wireless transmission systems composed of a few thousands of transistors, enabling the fabrication of wireless and chipless transceiver systems. The diode-capacitor interface was used to convert AC signals to DC signals and induce stimulus pulses at a sharp metal probe. A 400 MHz RF energy was wirelessly radiated from antennas and then stimulation pulses were observed at a sharp gold probe. A ˜5 m reading distance was obtained using a 1 mW power from a network analyzer. The cycles of electromagnetic (EM) radiation from an antenna were controlled by shielding the antenna with an EM absorber. Stimulation pulses with different amplitudes and durations were successfully observed at the probe. The obtained pulses were ˜0.08 mV in amplitude and 3-10 Hz in frequency. Coupling-of-mode (COM) and SPICE modeling simulations were also used to determine the optimal structural parameters for SAW delay line and the values of passive elements. On the basis of the extracted parameters, the entire system was experimentally implemented and characterized.

HPK1 competes with ADAP for SLP-76 binding and via Rap1 negatively affects T-cell adhesion.

PubMed

Patzak, Irene M; Königsberger, Sebastian; Suzuki, Akira; Mak, Tak W; Kiefer, Friedemann

2010-11-01

The hematopoietic progenitor kinase 1 (HPK1) signals into MAPK and NFκB pathways downstream of immunoreceptors, but enigmatically is a negative regulator of leukocytes. Here, we report a novel role for HPK1 in regulating the activation of the adhesion molecule leukocyte function-associated antigen-1 (LFA-1). Upon TCR stimulation, mediated by binding of adhesion and degranulation promoting adaptor protein (ADAP) to SLP-76, a ternary complex composed of ADAP/55-kDa src kinase associated phosphoprotein (SKAP-55) and RIAM translocates to the membrane and causes membrane recruitment of the active small GTPase Ras-related protein 1 (Rap1). Active Rap1, via its binding to RapL (regulator for cell adhesion and polarization enriched in lymphoid tissues), mediates LFA-1 integrin activation. We show here that HPK1, which also binds SLP-76, compete with ADAP for SLP-76 binding. In addition, HPK1 dampens Rap1 activation, resulting in decreased LFA-1 activity. Analysis of HPK1-deficient T cells revealed increased ADAP recruitment to SLP-76 and elevated Rap1 activation in those cells, leading to increased adhesion to ICAM-1 and cell spreading. Altogether, these results describe a novel function for HPK1 in linking TCR signaling to cell adhesion regulation and provide a mechanistic explanation for the negative regulatory role of HPK1 in T-cell biology.

Heterotrimeric G-Protein γ Subunit CsGG3.2 Positively Regulates the Expression of CBF Genes and Chilling Tolerance in Cucumber

PubMed Central

Bai, Longqiang; Liu, Yumei; Mu, Ying; Anwar, Ali; He, Chaoxing; Yan, Yan; Li, Yansu; Yu, Xianchang

2018-01-01

Heterotrimeric guanine nucleotide-binding proteins (G proteins) composed of alpha (Gα), beta (Gβ), and gamma (Gγ) subunits are central signal transducers mediating the cellular response to multiple stimuli, such as cold, in eukaryotes. Plant Gγ subunits, divided into A, B, and C three structurally distinct types, provide proper cellular localization and functional specificity to the heterotrimer complex. Here, we demonstrate that a type C Gγ subunit CsGG3.2 is involved in the regulation of the CBF regulon and plant tolerance to cold stresses in cucumber (Cucumis sativus L.). We showed that CsGG3.2 transcript abundance was positively induced by cold treatments. Transgenic cucumber plants (T1) constitutively over-expressing CsGG3.2 exhibits tolerance to chilling conditions and increased expression of CBF genes and their regulon. Antioxidative enzymes, i.e., superoxide dismutase, catalase, peroxidase, and glutathione reductase activities increased in cold-stressed transgenic plants. The reactive oxygen species, oxygen free radical and H2O2, production, as well as membrane lipid peroxidation (MDA) production decreased in transgenic plants, suggesting a better antioxidant system to cope the oxidative-damages caused by cold stress. These findings provide evidence for a critical role of CsGG3.2 in mediating cold signal transduction in plant cells. PMID:29719547

Herbivore diet breadth mediates the cascading effects of carnivores in food webs

PubMed Central

Singer, Michael S.; Lichter-Marck, Isaac H.; Farkas, Timothy E.; Aaron, Eric; Whitney, Kenneth D.; Mooney, Kailen A.

2014-01-01

Predicting the impact of carnivores on plants has challenged community and food web ecologists for decades. At the same time, the role of predators in the evolution of herbivore dietary specialization has been an unresolved issue in evolutionary ecology. Here, we integrate these perspectives by testing the role of herbivore diet breadth as a predictor of top-down effects of avian predators on herbivores and plants in a forest food web. Using experimental bird exclosures to study a complex community of trees, caterpillars, and birds, we found a robust positive association between caterpillar diet breadth (phylodiversity of host plants used) and the strength of bird predation across 41 caterpillar and eight tree species. Dietary specialization was associated with increased enemy-free space for both camouflaged (n = 33) and warningly signaled (n = 8) caterpillar species. Furthermore, dietary specialization was associated with increased crypsis (camouflaged species only) and more stereotyped resting poses (camouflaged and warningly signaled species), but was unrelated to caterpillar body size. These dynamics in turn cascaded down to plants: a metaanalysis (n = 15 tree species) showed the beneficial effect of birds on trees (i.e., reduced leaf damage) decreased with the proportion of dietary specialist taxa composing a tree species’ herbivore fauna. We conclude that herbivore diet breadth is a key functional trait underlying the trophic effects of carnivores on both herbivores and plants. PMID:24979778

Propagation path effects for rayleigh and love waves. Semi-annual technical report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herrin, E.; Goforth, T.

Seismic surface waves are usually composed of overlapping wave trains representing multi-path propagation. A first task in the analysis of such waves is to identify and separate the various component wave trains so that each can be analyzed separately. Phase-matched filters are a class of linear filters in which the Fourier phase of the filter is made equal to that of a given signal. The authors previously described an iterative technique which can be used to find a phase-matched filter for a particular component of a seismic signal. Application of the filters to digital records of Rayleigh waves allowed multiplemore » arrivals to be identified and removed, and allowed recovery of the complex spectrum of the primary wave train along with its apparent group velocity dispersion curve. A comparable analysis of Love waves presents additional complications. Love waves are contaminated by both Love and Rayleigh multipathing and by primary off-axis Rayleigh energy. In the case of explosions, there is much less energy generated as Love waves than as Rayleigh waves. The applicability of phase-matched filtering to Love waves is demonstrated by its use on earthquakes occurring in the Norwegian Sea and near Iceland and on a nuclear explosion in Novaya Zemlya. Despite severe multipathing in two of the three events, the amplitude and phase of each of the primary Love waves were recovered without significant distortion.« less

The Rac-GAP alpha2-chimaerin regulates hippocampal dendrite and spine morphogenesis.

PubMed

Valdez, Chris M; Murphy, Geoffrey G; Beg, Asim A

2016-09-01

Dendritic spines are fine neuronal processes where spatially restricted input can induce activity-dependent changes in one spine, while leaving neighboring spines unmodified. Morphological spine plasticity is critical for synaptic transmission and is thought to underlie processes like learning and memory. Significantly, defects in dendritic spine stability and morphology are common pathogenic features found in several neurodevelopmental and neuropsychiatric disorders. The remodeling of spines relies on proteins that modulate the underlying cytoskeleton, which is primarily composed of filamentous (F)-actin. The Rho-GTPase Rac1 is a major regulator of F-actin and is essential for the development and plasticity of dendrites and spines. However, the key molecules and mechanisms that regulate Rac1-dependent pathways at spines and synapses are not well understood. We have identified the Rac1-GTPase activating protein, α2-chimaerin, as a critical negative regulator of Rac1 in hippocampal neurons. The loss of α2-chimaerin significantly increases the levels of active Rac1 and induces the formation of aberrant polymorphic dendritic spines. Further, disruption of α2-chimaerin signaling simplifies dendritic arbor complexity and increases the presence of dendritic spines that appear poly-innervated. Our data suggests that α2-chimaerin serves as a "brake" to constrain Rac1-dependent signaling to ensure that the mature morphology of spines is maintained in response to network activity. Copyright © 2016 Elsevier Inc. All rights reserved.

Finite-difference time-domain modelling of through-the-Earth radio signal propagation

NASA Astrophysics Data System (ADS)

Ralchenko, M.; Svilans, M.; Samson, C.; Roper, M.

2015-12-01

This research seeks to extend the knowledge of how a very low frequency (VLF) through-the-Earth (TTE) radio signal behaves as it propagates underground, by calculating and visualizing the strength of the electric and magnetic fields for an arbitrary geology through numeric modelling. To achieve this objective, a new software tool has been developed using the finite-difference time-domain method. This technique is particularly well suited to visualizing the distribution of electromagnetic fields in an arbitrary geology. The frequency range of TTE radio (400-9000 Hz) and geometrical scales involved (1 m resolution for domains a few hundred metres in size) involves processing a grid composed of millions of cells for thousands of time steps, which is computationally expensive. Graphics processing unit acceleration was used to reduce execution time from days and weeks, to minutes and hours. Results from the new modelling tool were compared to three cases for which an analytic solution is known. Two more case studies were done featuring complex geologic environments relevant to TTE communications that cannot be solved analytically. There was good agreement between numeric and analytic results. Deviations were likely caused by numeric artifacts from the model boundaries; however, in a TTE application in field conditions, the uncertainty in the conductivity of the various geologic formations will greatly outweigh these small numeric errors.

Promising Properties and System Demonstration of an Environmentally Benign Yellow Smoke Formulation for Hand-Held Signals

DTIC Science & Technology

2014-04-18

differences between the current specification and this new baseline configuration: (1) The tube is now composed of cardboard instead of stainless steel ...version of this previously reported composition, one without fumed silica hereafter referred to as formulation A. This formulation consists of Solvent

The English Verb System.

ERIC Educational Resources Information Center

Gorayska, Barbara

1978-01-01

Techniques of teaching the English finite verb to speakers of other languages must account for meaning that is signalled by the structure alone and meaning derived from the context. Accordingly, this study attempts to distinguish the semantic components of the finite verb structure. The structure is viewed as being always composed of the following…

TRIM.FaTE Evaluation Report

EPA Pesticide Factsheets

The TRIM.FaTE Evaluation Report is composed of three volumes. Volume I presents conceptual, mechanistic, and structural complexity evaluations of various aspects of the model. Volumes II and III present performance evaluation.

Performance Analysis of a Hardware Implemented Complex Signal Kurtosis Radio-Frequency Interference Detector

NASA Technical Reports Server (NTRS)

Schoenwald, Adam J.; Bradley, Damon C.; Mohammed, Priscilla N.; Piepmeier, Jeffrey R.; Wong, Mark

2016-01-01

In the field of microwave radiometry, Radio Frequency Interference (RFI) consistently degrades the value of scientific results. Through the use of digital receivers and signal processing, the effects of RFI on scientific measurements can be reduced depending on certain circumstances. As technology allows us to implement wider band digital receivers for radiometry, the problem of RFI mitigation changes. Our work focuses on finding a detector that outperforms real kurtosis in wide band scenarios. The algorithm implemented is a complex signal kurtosis detector which was modeled and simulated. The performance of both complex and real signal kurtosis is evaluated for continuous wave, pulsed continuous wave, and wide band quadrature phase shift keying (QPSK) modulations. The use of complex signal kurtosis increased the detectability of interference.

Is sociality required for the evolution of communicative complexity? Evidence weighed against alternative hypotheses in diverse taxonomic groups

PubMed Central

Ord, Terry J.; Garcia-Porta, Joan

2012-01-01

Complex social communication is expected to evolve whenever animals engage in many and varied social interactions; that is, sociality should promote communicative complexity. Yet, informal comparisons among phylogenetically independent taxonomic groups seem to cast doubt on the putative role of social factors in the evolution of complex communication. Here, we provide a formal test of the sociality hypothesis alongside alternative explanations for the evolution of communicative complexity. We compiled data documenting variations in signal complexity among closely related species for several case study groups—ants, frogs, lizards and birds—and used new phylogenetic methods to investigate the factors underlying communication evolution. Social factors were only implicated in the evolution of complex visual signals in lizards. Ecology, and to some degree allometry, were most likely explanations for complexity in the vocal signals of frogs (ecology) and birds (ecology and allometry). There was some evidence for adaptive evolution in the pheromone complexity of ants, although no compelling selection pressure was identified. For most taxa, phylogenetic null models were consistently ranked above adaptive models and, for some taxa, signal complexity seems to have accumulated in species via incremental or random changes over long periods of evolutionary time. Becoming social presumably leads to the origin of social communication in animals, but its subsequent influence on the trajectory of signal evolution has been neither clear-cut nor general among taxonomic groups. PMID:22641820

Abnormal bias dependence of magnetoresistance in CoFeB/MgO/Si spin-injection tunnel contacts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, June-Young; Park, Byong-Guk, E-mail: bgpark@kaist.ac.kr; Baek, Seung-heon Chris

We report a strong bias voltage dependence of magnetoresistance (MR) in CoFeB/MgO/Si spin-injection tunnel contacts using the three-terminal Hanle geometry. When a bias voltage is relatively large, the MR is composed of two characteristic signals: a conventional Hanle signal observed at a low magnetic field, which is due to the precession of injected spins, and another signal originating from the rotation of the magnetization at a larger magnetic field. In contrast, for a small bias voltage, additional signals appear at a wide range of magnetic fields, which occasionally overwhelms the conventional Hanle signals. Because the additional signals are pronounced atmore » a low bias and are significantly reduced by annealing at moderate temperatures, they can be attributed to multi-step tunneling via defect states at the interfaces or tunnel barrier. Our results demonstrate that the spin injection signal caused by the defect states can be evaluated by its bias voltage dependence.« less

Crystallization and preliminary X-ray diffraction analysis of the CRISPR-Cas RNA-silencing Cmr complex.

PubMed

Osawa, Takuo; Inanaga, Hideko; Numata, Tomoyuki

2015-06-01

Clustered regularly interspaced short palindromic repeat (CRISPR)-derived RNA (crRNA) and CRISPR-associated (Cas) proteins constitute a prokaryotic adaptive immune system (CRISPR-Cas system) that targets and degrades invading genetic elements. The type III-B CRISPR-Cas Cmr complex, composed of the six Cas proteins (Cmr1-Cmr6) and a crRNA, captures and cleaves RNA complementary to the crRNA guide sequence. Here, a Cmr1-deficient functional Cmr (CmrΔ1) complex composed of Pyrococcus furiosus Cmr2-Cmr3, Archaeoglobus fulgidus Cmr4-Cmr5-Cmr6 and the 39-mer P. furiosus 7.01-crRNA was prepared. The CmrΔ1 complex was cocrystallized with single-stranded DNA (ssDNA) complementary to the crRNA guide by the vapour-diffusion method. The crystals diffracted to 2.1 Å resolution using synchrotron radiation at the Photon Factory. The crystals belonged to the triclinic space group P1, with unit-cell parameters a = 75.5, b = 76.2, c = 139.2 Å, α = 90.3, β = 104.8, γ = 118.6°. The asymmetric unit of the crystals is expected to contain one CmrΔ1-ssDNA complex, with a Matthews coefficient of 2.03 Å(3) Da(-1) and a solvent content of 39.5%.

A Saturn-Like Complex Composed of Macrocyclic Oligothiophene and C60 Fullerene: Structure, Stability, and Photophysical Properties in Solution and the Solid State.

PubMed

Shimizu, Hideyuki; Park, Kyu Hyung; Otani, Hiroyuki; Aoyagi, Shinobu; Nishinaga, Tohru; Aso, Yoshio; Kim, Dongho; Iyoda, Masahiko

2018-03-12

A Saturn-like 1:1 complex composed of macrocyclic oligothiophene E-8T7A and C 60 fullerene (C 60 ) was synthesized to investigate the interaction between macrocyclic oligothiophenes and C 60 in solution and the solid state. Because the Saturn-like 1:1 complex E-8T7A⋅C 60 is mainly stabilized by van der Waals interactions between C 60 and the sulfur atoms of the E-8T7A macrocycle, C 60 is rather weakly incorporated inside the macro-ring in solution. However, in the solid state the Saturn-like 1:1 complex preferentially formed single crystals or nanostructured polymorphs. Interestingly, X-ray analysis and theoretical calculations exhibited hindered rotation of C 60 in the Saturn-like complex due to interactions between C 60 and the sulfur atoms. Furthermore, the photoinduced charge transfer (CT) interaction between E-8T7A and C 60 in solution was investigated by using femtosecond transient absorption (TA) spectroscopy. The ultrafast TA spectral changes in the photoinduced absorption bands were attributed to the CT process in the Saturn-like structure. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

ATG13: just a companion, or an executor of the autophagic program?

PubMed

Alers, Sebastian; Wesselborg, Sebastian; Stork, Björn

2014-06-01

During the past 20 years, autophagy signaling has entered the main stage of the cell biological theater. Autophagy represents an intracellular degradation process that is involved in both the bulk recycling of cytoplasmic components and the selective removal of organelles, protein aggregates, or intracellular pathogens. The understanding of autophagy has been greatly facilitated by the characterization of the molecular machinery governing this process. In yeast, initiation of autophagy is controlled by the Atg1 kinase complex, which is composed of the Ser/Thr kinase Atg1, the adaptor protein Atg13, and the ternary complex of Atg17-Atg31-Atg29. In vertebrates, the orthologous ULK1 kinase complex contains the Ser/Thr kinase ULK1 and the accessory proteins ATG13, RB1CC1, and ATG101. Among these components, Atg1/ULK1 have gained major attention in the past, i.e., for the identification of upstream regulatory kinases, the characterization of downstream substrates controlling the autophagic flux, or as a druggable target for the modulation of autophagy. However, accumulating data indicate that the function of Atg13/ATG13 has been likely underestimated so far. In addition to ensuring proper Atg1/ULK1 recruitment and activity, this adaptor molecule has been implicated in ULK1-independent autophagy processes. Furthermore, recent data have identified additional binding partners of Atg13/ATG13 besides the components of the Atg1/ULK1 complex, e.g., Atg8 family proteins or acidic phospholipids. Therefore, in this review we will center the spotlight on Atg13/ATG13 and summarize the role that Atg13/ATG13 assumes in the autophagy stage play.

Pleiotropic and Epistatic Network-Based Discovery: Integrated Networks for Target Gene Discovery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weighill, Deborah; Jones, Piet; Shah, Manesh

Biological organisms are complex systems that are composed of functional networks of interacting molecules and macro-molecules. Complex phenotypes are the result of orchestrated, hierarchical, heterogeneous collections of expressed genomic variants. However, the effects of these variants are the result of historic selective pressure and current environmental and epigenetic signals, and, as such, their co-occurrence can be seen as genome-wide correlations in a number of different manners. Biomass recalcitrance (i.e., the resistance of plants to degradation or deconstruction, which ultimately enables access to a plant's sugars) is a complex polygenic phenotype of high importance to biofuels initiatives. This study makes usemore » of data derived from the re-sequenced genomes from over 800 different Populus trichocarpa genotypes in combination with metabolomic and pyMBMS data across this population, as well as co-expression and co-methylation networks in order to better understand the molecular interactions involved in recalcitrance, and identify target genes involved in lignin biosynthesis/degradation. A Lines Of Evidence (LOE) scoring system is developed to integrate the information in the different layers and quantify the number of lines of evidence linking genes to target functions. This new scoring system was applied to quantify the lines of evidence linking genes to lignin-related genes and phenotypes across the network layers, and allowed for the generation of new hypotheses surrounding potential new candidate genes involved in lignin biosynthesis in P. trichocarpa, including various AGAMOUS-LIKE genes. Lastly, the resulting Genome Wide Association Study networks, integrated with Single Nucleotide Polymorphism (SNP) correlation, co-methylation, and co-expression networks through the LOE scores are proving to be a powerful approach to determine the pleiotropic and epistatic relationships underlying cellular functions and, as such, the molecular basis for complex phenotypes, such as recalcitrance.« less

Pleiotropic and Epistatic Network-Based Discovery: Integrated Networks for Target Gene Discovery

DOE PAGES

Weighill, Deborah; Jones, Piet; Shah, Manesh; ...

2018-05-11

Biological organisms are complex systems that are composed of functional networks of interacting molecules and macro-molecules. Complex phenotypes are the result of orchestrated, hierarchical, heterogeneous collections of expressed genomic variants. However, the effects of these variants are the result of historic selective pressure and current environmental and epigenetic signals, and, as such, their co-occurrence can be seen as genome-wide correlations in a number of different manners. Biomass recalcitrance (i.e., the resistance of plants to degradation or deconstruction, which ultimately enables access to a plant's sugars) is a complex polygenic phenotype of high importance to biofuels initiatives. This study makes usemore » of data derived from the re-sequenced genomes from over 800 different Populus trichocarpa genotypes in combination with metabolomic and pyMBMS data across this population, as well as co-expression and co-methylation networks in order to better understand the molecular interactions involved in recalcitrance, and identify target genes involved in lignin biosynthesis/degradation. A Lines Of Evidence (LOE) scoring system is developed to integrate the information in the different layers and quantify the number of lines of evidence linking genes to target functions. This new scoring system was applied to quantify the lines of evidence linking genes to lignin-related genes and phenotypes across the network layers, and allowed for the generation of new hypotheses surrounding potential new candidate genes involved in lignin biosynthesis in P. trichocarpa, including various AGAMOUS-LIKE genes. Lastly, the resulting Genome Wide Association Study networks, integrated with Single Nucleotide Polymorphism (SNP) correlation, co-methylation, and co-expression networks through the LOE scores are proving to be a powerful approach to determine the pleiotropic and epistatic relationships underlying cellular functions and, as such, the molecular basis for complex phenotypes, such as recalcitrance.« less

Fractal Complexity-Based Feature Extraction Algorithm of Communication Signals

NASA Astrophysics Data System (ADS)

Wang, Hui; Li, Jingchao; Guo, Lili; Dou, Zheng; Lin, Yun; Zhou, Ruolin

How to analyze and identify the characteristics of radiation sources and estimate the threat level by means of detecting, intercepting and locating has been the central issue of electronic support in the electronic warfare, and communication signal recognition is one of the key points to solve this issue. Aiming at accurately extracting the individual characteristics of the radiation source for the increasingly complex communication electromagnetic environment, a novel feature extraction algorithm for individual characteristics of the communication radiation source based on the fractal complexity of the signal is proposed. According to the complexity of the received signal and the situation of environmental noise, use the fractal dimension characteristics of different complexity to depict the subtle characteristics of the signal to establish the characteristic database, and then identify different broadcasting station by gray relation theory system. The simulation results demonstrate that the algorithm can achieve recognition rate of 94% even in the environment with SNR of -10dB, and this provides an important theoretical basis for the accurate identification of the subtle features of the signal at low SNR in the field of information confrontation.

Effect of sound on gap-junction-based intercellular signaling: Calcium waves under acoustic irradiation.

PubMed

Deymier, P A; Swinteck, N; Runge, K; Deymier-Black, A; Hoying, J B

2015-01-01

We present a previously unrecognized effect of sound waves on gap-junction-based intercellular signaling such as in biological tissues composed of endothelial cells. We suggest that sound irradiation may, through temporal and spatial modulation of cell-to-cell conductance, create intercellular calcium waves with unidirectional signal propagation associated with nonconventional topologies. Nonreciprocity in calcium wave propagation induced by sound wave irradiation is demonstrated in the case of a linear and a nonlinear reaction-diffusion model. This demonstration should be applicable to other types of gap-junction-based intercellular signals, and it is thought that it should be of help in interpreting a broad range of biological phenomena associated with the beneficial therapeutic effects of sound irradiation and possibly the harmful effects of sound waves on health.

A critical role for PDGFRα signaling in medial nasal process development.

PubMed

He, Fenglei; Soriano, Philippe

2013-01-01

The primitive face is composed of neural crest cell (NCC) derived prominences. The medial nasal processes (MNP) give rise to the upper lip and vomeronasal organ, and are essential for normal craniofacial development, but the mechanism of MNP development remains largely unknown. PDGFRα signaling is known to be critical for NCC development and craniofacial morphogenesis. In this study, we show that PDGFRα is required for MNP development by maintaining the migration of progenitor neural crest cells (NCCs) and the proliferation of MNP cells. Further investigations reveal that PI3K/Akt and Rac1 signaling mediate PDGFRα function during MNP development. We thus establish PDGFRα as a novel regulator of MNP development and elucidate the roles of its downstream signaling pathways at cellular and molecular levels.

The Cell Wall Integrity Signaling Pathway and Its Involvement in Secondary Metabolite Production.

PubMed

Valiante, Vito

2017-12-06

The fungal cell wall is the external and first layer that fungi use to interact with the environment. Every stress signal, before being translated into an appropriate stress response, needs to overtake this layer. Many signaling pathways are involved in translating stress signals, but the cell wall integrity (CWI) signaling pathway is the one responsible for the maintenance and biosynthesis of the fungal cell wall. In fungi, the CWI signal is composed of a mitogen-activated protein kinase (MAPK) module. After the start of the phosphorylation cascade, the CWI signal induces the expression of cell-wall-related genes. However, the function of the CWI signal is not merely the activation of cell wall biosynthesis, but also the regulation of expression and production of specific molecules that are used by fungi to better compete in the environment. These molecules are normally defined as secondary metabolites or natural products. This review is focused on secondary metabolites affected by the CWI signal pathway with a special focus on relevant natural products such as melanins, mycotoxins, and antibacterial compounds.

[Cognitive aging mechanism of signaling effects on the memory for procedural sentences].

PubMed

Yamamoto, Hiroki; Shimada, Hideaki

2006-08-01

The aim of this study was to clarify the cognitive aging mechanism of signaling effects on the memory for procedural sentences. Participants were 60 younger adults (college students) and 60 older adults. Both age groups were assigned into two groups; half of each group was presented with procedural sentences with signals that highlighted their top-level structure and the other half with procedural sentences without them. Both groups were requested to perform the sentence arrangement task and the reconstruction task. Each task was composed of procedural sentences with or without signals. Results indicated that signaling supported changes in strategy utilization during the successive organizational processes and that changes in strategy utilization resulting from signaling improved the memory for procedural sentences. Moreover, age-related factors interfered with these signaling effects. This study clarified the cognitive aging mechanism of signaling effects in which signaling supports changes in the strategy utilization during organizational processes at encoding and this mediation promotes memory for procedural sentences, though disuse of the strategy utilization due to aging restrains their memory for procedural sentences.

Matching synchrosqueezing transform: A useful tool for characterizing signals with fast varying instantaneous frequency and application to machine fault diagnosis

NASA Astrophysics Data System (ADS)

Wang, Shibin; Chen, Xuefeng; Selesnick, Ivan W.; Guo, Yanjie; Tong, Chaowei; Zhang, Xingwu

2018-02-01

Synchrosqueezing transform (SST) can effectively improve the readability of the time-frequency (TF) representation (TFR) of nonstationary signals composed of multiple components with slow varying instantaneous frequency (IF). However, for signals composed of multiple components with fast varying IF, SST still suffers from TF blurs. In this paper, we introduce a time-frequency analysis (TFA) method called matching synchrosqueezing transform (MSST) that achieves a highly concentrated TF representation comparable to the standard TF reassignment methods (STFRM), even for signals with fast varying IF, and furthermore, MSST retains the reconstruction benefit of SST. MSST captures the philosophy of STFRM to simultaneously consider time and frequency variables, and incorporates three estimators (i.e., the IF estimator, the group delay estimator, and a chirp-rate estimator) into a comprehensive and accurate IF estimator. In this paper, we first introduce the motivation of MSST with three heuristic examples. Then we introduce a precise mathematical definition of a class of chirp-like intrinsic-mode-type functions that locally can be viewed as a sum of a reasonably small number of approximate chirp signals, and we prove that MSST does indeed succeed in estimating chirp-rate and IF of arbitrary functions in this class and succeed in decomposing these functions. Furthermore, we describe an efficient numerical algorithm for the practical implementation of the MSST, and we provide an adaptive IF extraction method for MSST reconstruction. Finally, we verify the effectiveness of the MSST in practical applications for machine fault diagnosis, including gearbox fault diagnosis for a wind turbine in variable speed conditions and rotor rub-impact fault diagnosis for a dual-rotor turbofan engine.

Chapter 4. Cytomechanics of hair basics of the mechanical stability.

PubMed

Popescu, Crisan; Höcker, Hartwig

2009-01-01

Hair is a complex "cornified" multicellular tissue composed of cuticle and cortex cells mechanically acting as a whole. The cuticle cells overlap and cortex cells interdigitate, all cells being composed of different morphological elements and separated by the cell membrane complex (CMC). The CMC and the morphological elements of the cortex cells, the macrofibrils, composed of microfibrils or intermediate filaments (IFs), and the intermacrofibrillar and intermicrofibrillar cement or the amorphous matrix material determine the mechanical properties of hair. The IFs consist of alpha-keratin molecules being arranged in a sophisticated way of two parallel monomers and antiparallel and shifted dimers rationalized by the amino acid composition and sequence. The mechanical properties of hair result from mechanical interlocking effects, hydrophobic effects, hydrogen bridges, Coulombic interactions, and (covalent) isodipeptide and, in particular, disulfide bridges on a molecular level. The mechanical models applied to hair are based on a simple two-component system, the microfibril/matrix structure. An important regime of the stress-strain curve is the transition of the molecules of the microfibrils from the alpha-helical to the beta-sheet structure. Due to the longitudinal orientation of the IF molecules the longitudinal swelling of the fibers in water is negligible, the radial swelling, however, is substantial.

ATM-Dependent Phosphorylation of All Three Members of the MRN Complex: From Sensor to Adaptor.

PubMed

Lavin, Martin F; Kozlov, Sergei; Gatei, Magtouf; Kijas, Amanda W

2015-10-23

The recognition, signalling and repair of DNA double strand breaks (DSB) involves the participation of a multitude of proteins and post-translational events that ensure maintenance of genome integrity. Amongst the proteins involved are several which when mutated give rise to genetic disorders characterised by chromosomal abnormalities, cancer predisposition, neurodegeneration and other pathologies. ATM (mutated in ataxia-telangiectasia (A-T) and members of the Mre11/Rad50/Nbs1 (MRN complex) play key roles in this process. The MRN complex rapidly recognises and locates to DNA DSB where it acts to recruit and assist in ATM activation. ATM, in the company of several other DNA damage response proteins, in turn phosphorylates all three members of the MRN complex to initiate downstream signalling. While ATM has hundreds of substrates, members of the MRN complex play a pivotal role in mediating the downstream signalling events that give rise to cell cycle control, DNA repair and ultimately cell survival or apoptosis. Here we focus on the interplay between ATM and the MRN complex in initiating signaling of breaks and more specifically on the adaptor role of the MRN complex in mediating ATM signalling to downstream substrates to control different cellular processes.

Nutrient Regulation of the mTOR Complex 1 Signaling Pathway

PubMed Central

Kim, Sang Gyun; Buel, Gwen R.; Blenis, John

2013-01-01

The mammalian target of rapamycin (mTOR) is an evolutionally conserved kinase which exists in two distinct structural and functional complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Of the two complexes, mTORC1 couples nutrient abundance to cell growth and proliferation by sensing and integrating a variety of inputs arising from amino acids, cellular stresses, energy status, and growth factors. Defects in mTORC1 regulation are implicated in the development of many metabolic diseases, including cancer and diabetes. Over the past decade, significant advances have been made in deciphering the complexity of the signaling processes contributing to mTORC1 regulation and function, but the mechanistic details are still not fully understood. In particular, how amino acid availability is sensed by cells and signals to mTORC1 remains unclear. In this review, we discuss the current understanding of nutrient-dependent control of mTORC1 signaling and will focus on the key components involved in amino acid signaling to mTORC1. PMID:23694989

Glycans – the third revolution in evolution

PubMed Central

Lauc, Gordan; Krištić, Jasminka; Zoldoš, Vlatka

2014-01-01

The development and maintenance of a complex organism composed of trillions of cells is an extremely complex task. At the molecular level every process requires a specific molecular structures to perform it, thus it is difficult to imagine how less than tenfold increase in the number of genes between simple bacteria and higher eukaryotes enabled this quantum leap in complexity. In this perspective article we present the hypothesis that the invention of glycans was the third revolution in evolution (the appearance of nucleic acids and proteins being the first two), which enabled the creation of novel molecular entities that do not require a direct genetic template. Contrary to proteins and nucleic acids, which are made from a direct DNA template, glycans are product of a complex biosynthetic pathway affected by hundreds of genetic and environmental factors. Therefore glycans enable adaptive response to environmental changes and, unlike other epiproteomic modifications, which act as off/on switches, glycosylation significantly contributes to protein structure and enables novel functions. The importance of glycosylation is evident from the fact that nearly all proteins invented after the appearance of multicellular life are composed of both polypeptide and glycan parts. PMID:24904645

Dynamic complexity: plant receptor complexes at the plasma membrane.

PubMed

Burkart, Rebecca C; Stahl, Yvonne

2017-12-01

Plant receptor complexes at the cell surface perceive many different external and internal signalling molecules and relay these signals into the cell to regulate development, growth and immunity. Recent progress in the analyses of receptor complexes using different live cell imaging approaches have shown that receptor complex formation and composition are dynamic and take place at specific microdomains at the plasma membrane. In this review we focus on three prominent examples of Arabidopsis thaliana receptor complexes and how their dynamic spatio-temporal distribution at the PM has been studied recently. We will elaborate on the newly emerging concept of plasma membrane microdomains as potential hubs for specific receptor complex assembly and signalling outputs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Binding of Signal Recognition Particle Gives Ribosome/Nascent Chain Complexes a Competitive Advantage in Endoplasmic Reticulum Membrane Interaction

PubMed Central

Neuhof, Andrea; Rolls, Melissa M.; Jungnickel, Berit; Kalies, Kai-Uwe; Rapoport, Tom A.

1998-01-01

Most secretory and membrane proteins are sorted by signal sequences to the endoplasmic reticulum (ER) membrane early during their synthesis. Targeting of the ribosome-nascent chain complex (RNC) involves the binding of the signal sequence to the signal recognition particle (SRP), followed by an interaction of ribosome-bound SRP with the SRP receptor. However, ribosomes can also independently bind to the ER translocation channel formed by the Sec61p complex. To explain the specificity of membrane targeting, it has therefore been proposed that nascent polypeptide-associated complex functions as a cytosolic inhibitor of signal sequence- and SRP-independent ribosome binding to the ER membrane. We report here that SRP-independent binding of RNCs to the ER membrane can occur in the presence of all cytosolic factors, including nascent polypeptide-associated complex. Nontranslating ribosomes competitively inhibit SRP-independent membrane binding of RNCs but have no effect when SRP is bound to the RNCs. The protective effect of SRP against ribosome competition depends on a functional signal sequence in the nascent chain and is also observed with reconstituted proteoliposomes containing only the Sec61p complex and the SRP receptor. We conclude that cytosolic factors do not prevent the membrane binding of ribosomes. Instead, specific ribosome targeting to the Sec61p complex is provided by the binding of SRP to RNCs, followed by an interaction with the SRP receptor, which gives RNC–SRP complexes a selective advantage in membrane targeting over nontranslating ribosomes. PMID:9436994

Dynamic force signal processing system of a robot manipulator

NASA Technical Reports Server (NTRS)

Uchiyama, M.; Kitagaki, K.; Hakomori, K.

1987-01-01

If dynamic noises such as those caused by the inertia forces of the hand can be eliminated from the signal of the force sensor installed on the wrist of the robot manipulator and if the necessary information of the external force can be detected with high sensitivity and high accuracy, a fine force feedback control for robots used in high speed and various fields will be possible. As the dynamic force sensing system, an external force estimate method with the extended Kalman filter is suggested and simulations and tests for a one axis force were performed. Later a dynamic signal processing system of six axes was composed and tested. The results are presented.

Design of remote control alarm system by microwave detection

NASA Astrophysics Data System (ADS)

Wang, Junli

2018-04-01

A microwave detection remote control alarm system is designed, which is composed of a Microwave detectors, a radio receiving/transmitting module and a digital encoding/decoding IC. When some objects move into the surveillance area, microwave detectors will generate a control signal to start transmitting system. A radio control signal will be spread by the transmitting module, once the signal can be received, and it will be disposed by some circuits, arousing some voices that awake the watching people. The whole device is a modular configuration, it not only has some advantage of frequency stable, but also reliable and adjustment-free, and it is suitable for many kinds of demands within the distance of 100m.

Purification of polymorphic components of complex genomes

DOEpatents

Stodolsky, Marvin

1991-01-01

A method is disclosed for processing related subject and reference macromolecule populations composed of complementary strands into their respective subject and reference populations of representative fragments and effectuating purification of unique polymorphic subject fragments.

Purification of polymorphic components of complex genomes

DOEpatents

Stodolsky, M.

1988-01-21

A method for processing related subject and reference macromolecule composed of complementary strand into their respective subject and reference populations of representative fragments and effectuating purification of unique polymorphic subject fragments. 1 fig.

Composing Music with Complex Networks

NASA Astrophysics Data System (ADS)

Liu, Xiaofan; Tse, Chi K.; Small, Michael

In this paper we study the network structure in music and attempt to compose music artificially. Networks are constructed with nodes and edges corresponding to musical notes and their co-occurrences. We analyze sample compositions from Bach, Mozart, Chopin, as well as other types of music including Chinese pop music. We observe remarkably similar properties in all networks constructed from the selected compositions. Power-law exponents of degree distributions, mean degrees, clustering coefficients, mean geodesic distances, etc. are reported. With the network constructed, music can be created by using a biased random walk algorithm, which begins with a randomly chosen note and selects the subsequent notes according to a simple set of rules that compares the weights of the edges, weights of the nodes, and/or the degrees of nodes. The newly created music from complex networks will be played in the presentation.

Epigenomics and the concept of degeneracy in biological systems

PubMed Central

Mason, Paul H.; Barron, Andrew B.

2014-01-01

Researchers in the field of epigenomics are developing more nuanced understandings of biological complexity, and exploring the multiple pathways that lead to phenotypic expression. The concept of degeneracy—referring to the multiple pathways that a system recruits to achieve functional plasticity—is an important conceptual accompaniment to the growing body of knowledge in epigenomics. Distinct from degradation, redundancy and dilapidation; degeneracy refers to the plasticity of traits whose function overlaps in some environments, but diverges in others. While a redundant system is composed of repeated identical elements performing the same function, a degenerate system is composed of different elements performing similar or overlapping functions. Here, we describe the degenerate structure of gene regulatory systems from the basic genetic code to flexible epigenomic modifications, and discuss how these structural features have contributed to organism complexity, robustness, plasticity and evolvability. PMID:24335757

Research on wheelchair robot control system based on EOG

NASA Astrophysics Data System (ADS)

Xu, Wang; Chen, Naijian; Han, Xiangdong; Sun, Jianbo

2018-04-01

The paper describes an intelligent wheelchair control system based on EOG. It can help disabled people improve their living ability. The system can acquire EOG signal from the user, detect the number of blink and the direction of glancing, and then send commands to the wheelchair robot via RS-232 to achieve the control of wheelchair robot. Wheelchair robot control system based on EOG is composed of processing EOG signal and human-computer interactive technology, which achieves a purpose of using conscious eye movement to control wheelchair robot.

Causal agents of Fusarium head blight of durum wheat (Triticum durum Desf.) in central Italy and their in vitro biosynthesis of secondary metabolites.

PubMed

Beccari, G; Colasante, V; Tini, F; Senatore, M T; Prodi, A; Sulyok, M; Covarelli, L

2018-04-01

Durum wheat samples harvested in central Italy (Umbria) were analyzed to: evaluate the occurrence of the fungal community in the grains, molecularly identify the Fusarium spp. which are part of the Fusarium head blight (FHB) complex and characterize the in vitro secondary metabolite profiles of a subset of Fusarium strains. The Fusarium genus was one of the main components of the durum wheat fungal community. The FHB complex was composed of eight species: Fusarium avenaceum (61%), F. graminearum (22%), F. poae (9%), F. culmorum (4%), F. proliferatum (2%), F. sporotrichioides (1%), F. sambucinum (0.5%) and F. langsethiae (0.5%). F. graminearum population was mainly composed of the 15-acetyldeoxynivalenol chemotype, while, F. culmorum population was composed of the 3-acetyldeoxynivalenol chemotype. In vitro characterization of secondary metabolite biosynthesis was conducted for a wide spectrum of substances, showing the mycotoxigenic potential of the species complex. F. avenaceum strains were characterized by high enniantin and moniliformin production. F. graminearum strains were in prevalence deoxynivalenol producers. F. poae strains were characterized by a high biosynthesis of beauvericin like the F. sporotrichioides strain which was also found to be a high T-2/HT-2 toxins producer. Production of aurofusarin, butenolide, gibepyrone D, fusarin C, apicidin was also reported for the analyzed strains. Copyright © 2017 Elsevier Ltd. All rights reserved.

Organic and inorganic decomposition products from the thermal desorption of atmospheric particles

NASA Astrophysics Data System (ADS)

Williams, B. J.; Zhang, Y.; Zuo, X.; Martinez, R. E.; Walker, M. J.; Kreisberg, N. M.; Goldstein, A. H.; Docherty, K. S.; Jimenez, J. L.

2015-12-01

Atmospheric aerosol composition is often analyzed using thermal desorption techniques to evaporate samples and deliver organic or inorganic molecules to various designs of detectors for identification and quantification. The organic aerosol (OA) fraction is composed of thousands of individual compounds, some with nitrogen- and sulfur-containing functionality, and often contains oligomeric material, much of which may be susceptible to decomposition upon heating. Here we analyze thermal decomposition products as measured by a thermal desorption aerosol gas chromatograph (TAG) capable of separating thermal decomposition products from thermally stable molecules. The TAG impacts particles onto a collection and thermal desorption (CTD) cell, and upon completion of sample collection, heats and transfers the sample in a helium flow up to 310 °C. Desorbed molecules are refocused at the head of a GC column that is held at 45 °C and any volatile decomposition products pass directly through the column and into an electron impact quadrupole mass spectrometer (MS). Analysis of the sample introduction (thermal decomposition) period reveals contributions of NO+ (m/z 30), NO2+ (m/z 46), SO+ (m/z 48), and SO2+ (m/z 64), derived from either inorganic or organic particle-phase nitrate and sulfate. CO2+ (m/z 44) makes up a major component of the decomposition signal, along with smaller contributions from other organic components that vary with the type of aerosol contributing to the signal (e.g., m/z 53, 82 observed here for isoprene-derived secondary OA). All of these ions are important for ambient aerosol analyzed with the aerosol mass spectrometer (AMS), suggesting similarity of the thermal desorption processes in both instruments. Ambient observations of these decomposition products compared to organic, nitrate, and sulfate mass concentrations measured by an AMS reveal good correlation, with improved correlations for OA when compared to the AMS oxygenated OA (OOA) component. TAG signal found in the traditional compound elution time period reveals higher correlations with AMS hydrocarbon-like OA (HOA) combined with the fraction of OOA that is less oxygenated. Potential to quantify nitrate and sulfate aerosol mass concentrations using the TAG system is explored through analysis of ammonium sulfate and ammonium nitrate standards. While chemical standards display a linear response in the TAG system, re-desorptions of the CTD cell following ambient sample analysis shows some signal carryover on sulfate and organics, and new desorption methods should be developed to improve throughput. Future standards should be composed of complex organic/inorganic mixtures, similar to what is found in the atmosphere, and perhaps will more accurately account for any aerosol mixture effects on compositional quantification.

Organic and inorganic decomposition products from the thermal desorption of atmospheric particles

NASA Astrophysics Data System (ADS)

Williams, Brent J.; Zhang, Yaping; Zuo, Xiaochen; Martinez, Raul E.; Walker, Michael J.; Kreisberg, Nathan M.; Goldstein, Allen H.; Docherty, Kenneth S.; Jimenez, Jose L.

2016-04-01

Atmospheric aerosol composition is often analyzed using thermal desorption techniques to evaporate samples and deliver organic or inorganic molecules to various designs of detectors for identification and quantification. The organic aerosol (OA) fraction is composed of thousands of individual compounds, some with nitrogen- and sulfur-containing functionality and, often contains oligomeric material, much of which may be susceptible to decomposition upon heating. Here we analyze thermal decomposition products as measured by a thermal desorption aerosol gas chromatograph (TAG) capable of separating thermal decomposition products from thermally stable molecules. The TAG impacts particles onto a collection and thermal desorption (CTD) cell, and upon completion of sample collection, heats and transfers the sample in a helium flow up to 310 °C. Desorbed molecules are refocused at the head of a gas chromatography column that is held at 45 °C and any volatile decomposition products pass directly through the column and into an electron impact quadrupole mass spectrometer. Analysis of the sample introduction (thermal decomposition) period reveals contributions of NO+ (m/z 30), NO2+ (m/z 46), SO+ (m/z 48), and SO2+ (m/z 64), derived from either inorganic or organic particle-phase nitrate and sulfate. CO2+ (m/z 44) makes up a major component of the decomposition signal, along with smaller contributions from other organic components that vary with the type of aerosol contributing to the signal (e.g., m/z 53, 82 observed here for isoprene-derived secondary OA). All of these ions are important for ambient aerosol analyzed with the aerosol mass spectrometer (AMS), suggesting similarity of the thermal desorption processes in both instruments. Ambient observations of these decomposition products compared to organic, nitrate, and sulfate mass concentrations measured by an AMS reveal good correlation, with improved correlations for OA when compared to the AMS oxygenated OA (OOA) component. TAG signal found in the traditional compound elution time period reveals higher correlations with AMS hydrocarbon-like OA (HOA) combined with the fraction of OOA that is less oxygenated. Potential to quantify nitrate and sulfate aerosol mass concentrations using the TAG system is explored through analysis of ammonium sulfate and ammonium nitrate standards. While chemical standards display a linear response in the TAG system, redesorptions of the CTD cell following ambient sample analysis show some signal carryover on sulfate and organics, and new desorption methods should be developed to improve throughput. Future standards should be composed of complex organic/inorganic mixtures, similar to what is found in the atmosphere, and perhaps will more accurately account for any aerosol mixture effects on compositional quantification.

Organic and inorganic decomposition products from the thermal desorption of atmospheric particles

DOE PAGES

Williams, Brent J.; Zhang, Yaping; Zuo, Xiaochen; ...

2016-04-11

Here, atmospheric aerosol composition is often analyzed using thermal desorption techniques to evaporate samples and deliver organic or inorganic molecules to various designs of detectors for identification and quantification. The organic aerosol (OA) fraction is composed of thousands of individual compounds, some with nitrogen- and sulfur-containing functionality and, often contains oligomeric material, much of which may be susceptible to decomposition upon heating. Here we analyze thermal decomposition products as measured by a thermal desorption aerosol gas chromatograph (TAG) capable of separating thermal decomposition products from thermally stable molecules. The TAG impacts particles onto a collection and thermal desorption (CTD) cell, and upon completionmore » of sample collection, heats and transfers the sample in a helium flow up to 310 °C. Desorbed molecules are refocused at the head of a gas chromatography column that is held at 45 °C and any volatile decomposition products pass directly through the column and into an electron impact quadrupole mass spectrometer. Analysis of the sample introduction (thermal decomposition) period reveals contributions of NO + ( m/z 30), NO 2 + ( m/z 46), SO + ( m/z 48), and SO 2 + ( m/z 64), derived from either inorganic or organic particle-phase nitrate and sulfate. CO 2 + ( m/z 44) makes up a major component of the decomposition signal, along with smaller contributions from other organic components that vary with the type of aerosol contributing to the signal (e.g., m/z 53, 82 observed here for isoprene-derived secondary OA). All of these ions are important for ambient aerosol analyzed with the aerosol mass spectrometer (AMS), suggesting similarity of the thermal desorption processes in both instruments. Ambient observations of these decomposition products compared to organic, nitrate, and sulfate mass concentrations measured by an AMS reveal good correlation, with improved correlations for OA when compared to the AMS oxygenated OA (OOA) component. TAG signal found in the traditional compound elution time period reveals higher correlations with AMS hydrocarbon-like OA (HOA) combined with the fraction of OOA that is less oxygenated. Potential to quantify nitrate and sulfate aerosol mass concentrations using the TAG system is explored through analysis of ammonium sulfate and ammonium nitrate standards. While chemical standards display a linear response in the TAG system, redesorptions of the CTD cell following ambient sample analysis show some signal carryover on sulfate and organics, and new desorption methods should be developed to improve throughput. Future standards should be composed of complex organic/inorganic mixtures, similar to what is found in the atmosphere, and perhaps will more accurately account for any aerosol mixture effects on compositional quantification.« less

My Corporis Fabrica: an ontology-based tool for reasoning and querying on complex anatomical models

PubMed Central

2014-01-01

Background Multiple models of anatomy have been developed independently and for different purposes. In particular, 3D graphical models are specially useful for visualizing the different organs composing the human body, while ontologies such as FMA (Foundational Model of Anatomy) are symbolic models that provide a unified formal description of anatomy. Despite its comprehensive content concerning the anatomical structures, the lack of formal descriptions of anatomical functions in FMA limits its usage in many applications. In addition, the absence of connection between 3D models and anatomical ontologies makes it difficult and time-consuming to set up and access to the anatomical content of complex 3D objects. Results First, we provide a new ontology of anatomy called My Corporis Fabrica (MyCF), which conforms to FMA but extends it by making explicit how anatomical structures are composed, how they contribute to functions, and also how they can be related to 3D complex objects. Second, we have equipped MyCF with automatic reasoning capabilities that enable model checking and complex queries answering. We illustrate the added-value of such a declarative approach for interactive simulation and visualization as well as for teaching applications. Conclusions The novel vision of ontologies that we have developed in this paper enables a declarative assembly of different models to obtain composed models guaranteed to be anatomically valid while capturing the complexity of human anatomy. The main interest of this approach is its declarativity that makes possible for domain experts to enrich the knowledge base at any moment through simple editors without having to change the algorithmic machinery. This provides MyCF software environment a flexibility to process and add semantics on purpose for various applications that incorporate not only symbolic information but also 3D geometric models representing anatomical entities as well as other symbolic information like the anatomical functions. PMID:24936286

Network complexity as a measure of information processing across resting-state networks: evidence from the Human Connectome Project

PubMed Central

McDonough, Ian M.; Nashiro, Kaoru

2014-01-01

An emerging field of research focused on fluctuations in brain signals has provided evidence that the complexity of those signals, as measured by entropy, conveys important information about network dynamics (e.g., local and distributed processing). While much research has focused on how neural complexity differs in populations with different age groups or clinical disorders, substantially less research has focused on the basic understanding of neural complexity in populations with young and healthy brain states. The present study used resting-state fMRI data from the Human Connectome Project (Van Essen et al., 2013) to test the extent that neural complexity in the BOLD signal, as measured by multiscale entropy (1) would differ from random noise, (2) would differ between four major resting-state networks previously associated with higher-order cognition, and (3) would be associated with the strength and extent of functional connectivity—a complementary method of estimating information processing. We found that complexity in the BOLD signal exhibited different patterns of complexity from white, pink, and red noise and that neural complexity was differentially expressed between resting-state networks, including the default mode, cingulo-opercular, left and right frontoparietal networks. Lastly, neural complexity across all networks was negatively associated with functional connectivity at fine scales, but was positively associated with functional connectivity at coarse scales. The present study is the first to characterize neural complexity in BOLD signals at a high temporal resolution and across different networks and might help clarify the inconsistencies between neural complexity and functional connectivity, thus informing the mechanisms underlying neural complexity. PMID:24959130

Ring-fault activity at subsiding calderas studied from analogue experiments and numerical modeling

NASA Astrophysics Data System (ADS)

Liu, Y. K.; Ruch, J.; Vasyura-Bathke, H.; Jonsson, S.

2017-12-01

Several subsiding calderas, such as the ones in the Galápagos archipelago and the Axial seamount in the Pacific Ocean have shown a complex but similar ground deformation pattern, composed of a broad deflation signal affecting the entire volcanic edifice and of a localized subsidence signal focused within the caldera. However, it is still debated how deep processes at subsiding calderas, including magmatic pressure changes, source locations and ring-faulting, relate to this observed surface deformation pattern. We combine analogue sandbox experiments with numerical modeling to study processes involved from initial subsidence to later collapse of calderas. The sandbox apparatus is composed of a motor driven subsiding half-piston connected to the bottom of a glass box. During the experiments the observation is done by five digital cameras photographing from various perspectives. We use Photoscan, a photogrammetry software and PIVLab, a time-resolved digital image correlation tool, to retrieve time-series of digital elevation models and velocity fields from acquired photographs. This setup allows tracking the processes acting both at depth and at the surface, and to assess their relative importance as the subsidence evolves to a collapse. We also use the Boundary Element Method to build a numerical model of the experiment setup, which comprises contracting sill-like source in interaction with a ring-fault in elastic half-space. We then compare our results from these two approaches with the examples observed in nature. Our preliminary experimental and numerical results show that at the initial stage of magmatic withdrawal, when the ring-fault is not yet well formed, broad and smooth deflation dominates at the surface. As the withdrawal increases, narrower subsidence bowl develops accompanied by the upward propagation of the ring-faulting. This indicates that the broad deflation, affecting the entire volcano edifice, is primarily driven by the contraction of the magmatic source, whereas the ring-faulting tends to concentrate deformation within the caldera. This interaction between ring-faulting and pressure decrease in a magma reservoir therefore provides a possible explanation for the deformation pattern observed at several subsiding calderas.

Insulin-like Growth Factor (IGF) Signaling Requires αvβ3-IGF1-IGF Type 1 Receptor (IGF1R) Ternary Complex Formation in Anchorage Independence, and the Complex Formation Does Not Require IGF1R and Src Activation

PubMed Central

Fujita, Masaaki; Takada, Yoko K.; Takada, Yoshikazu

2013-01-01

Integrin αvβ3 plays a role in insulin-like growth factor 1 (IGF1) signaling (integrin-IGF1 receptor (IGF1R) cross-talk) in non-transformed cells in anchorage-dependent conditions. We reported previously that IGF1 directly binds to αvβ3 and induces αvβ3-IGF1-IGF1R ternary complex formation in these conditions. The integrin-binding defective IGF1 mutant (R36E/R37E) is defective in inducing ternary complex formation and IGF signaling, whereas it still binds to IGF1R. We studied if IGF1 can induce signaling in anchorage-independent conditions in transformed Chinese hamster ovary cells that express αvβ3 (β3-CHO) cells. Here we describe that IGF1 signals were more clearly detectable in anchorage-independent conditions (polyHEMA-coated plates) than in anchorage-dependent conditions. This suggests that IGF signaling is masked by signals from cell-matrix interaction in anchorage-dependent conditions. IGF signaling required αvβ3 expression, and R36E/R37E was defective in inducing signals in polyHEMA-coated plates. These results suggest that αvβ3-IGF1 interaction, not αvβ3-extracellular matrix interaction, is essential for IGF signaling. Inhibitors of IGF1R, Src, AKT, and ERK1/2 did not suppress αvβ3-IGF-IGF1R ternary complex formation, suggesting that activation of these kinases are not required for ternary complex formation. Also, mutations of the β3 cytoplasmic tail (Y747F and Y759F) that block β3 tyrosine phosphorylation did not affect IGF1R phosphorylation or AKT activation. We propose a model in which IGF1 binding to IGF1R induces recruitment of integrin αvβ3 to the IGF-IGF1R complex and then β3 and IGF1R are phosphorylated. It is likely that αvβ3 should be together with the IGF1-IGF1R complex for triggering IGF signaling. PMID:23243309

41 CFR 50-204.24 - Caution signs, labels, and signals.

Code of Federal Regulations, 2010 CFR

2010-07-01

... established for a period of 30 days or less, such control device is not required. (d) Airborne radioactivity area. (1) As used in the provisions of this subpart, “airborne radioactivity area” means (i) any room, enclosure, or operating area in which airborne radioactive materials, composed wholly or partly of...

Grid-Independent Compressive Imaging and Fourier Phase Retrieval

ERIC Educational Resources Information Center

Liao, Wenjing

2013-01-01

This dissertation is composed of two parts. In the first part techniques of band exclusion(BE) and local optimization(LO) are proposed to solve linear continuum inverse problems independently of the grid spacing. The second part is devoted to the Fourier phase retrieval problem. Many situations in optics, medical imaging and signal processing call…

Symmetric/Asymmetrical SIRs Dual-Band BPF Design for WLAN Applications

NASA Astrophysics Data System (ADS)

Ho, Min-Hua; Ho, Hao-Hung; Chen, Mingchih

This paper presents the dual-band bandpass filters (BPFs) design composed of λ/2 and symmetrically/asymmetrically paired λ/4 stepped impedance resonators (SIRs) for the WLAN applications. The filters cover both the operating frequencies of 2.45 and 5.2GHz. The dual-coupling mechanism is used in the filter design to provide alternative routes for signals of selected frequencies. A prototype filter is composed of λ/2 and symmetrical λ/4 SIRs. The enhanced wide-stopband filter is then developed from the filter with the symmetrical λ/4 SIRs replaced by the asymmetrical ones. The asymmetrical λ/4 SIRs have their higher resonances frequencies isolated from the adjacent I/O SIRs and extend the enhanced filter an upper stopband limit beyond ten time the fundamental frequency. Also, the filter might possess a cross-coupling structure which introduces transmission zeros by the passband edges to improve the signal selectivity. The tapped-line feed is adopted in this circuit to create additional attenuation poles for improving the stopband rejection levels. Experiments are conducted to verify the circuit performance.

Mathematic modeling of complex aquifer: Evian Natural Mineral Water case study considering lumped and distributed models.

NASA Astrophysics Data System (ADS)

Henriot, abel; Blavoux, bernard; Travi, yves; Lachassagne, patrick; Beon, olivier; Dewandel, benoit; Ladouche, bernard

2013-04-01

The Evian Natural Mineral Water (NMW) aquifer is a highly heterogeneous Quaternary glacial deposits complex composed of three main units, from bottom to top: - The "Inferior Complex" mainly composed of basal and impermeable till lying on the Alpine rocks. It outcrops only at the higher altitudes but is known in depth through drilled holes. - The "Gavot Plateau Complex" is an interstratified complex of mainly basal and lateral till up to 400 m thick. It outcrops at heights above approximately 850 m a.m.s.l. and up to 1200 m a.m.s.l. over a 30 km² area. It is the main recharge area known for the hydromineral system. - The "Terminal Complex" from which the Evian NMW is emerging at 410 m a.m.s.l. It is composed of sand and gravel Kame terraces that allow water to flow from the deep "Gavot Plateau Complex" permeable layers to the "Terminal Complex". A thick and impermeable terminal till caps and seals the system. Aquifer is then confined at its downstream area. Because of heterogeneity and complexity of this hydrosystem, distributed modeling tools are difficult to implement at the whole system scale: important hypothesis would have to be made about geometry, hydraulic properties, boundary conditions for example and extrapolation would lead with no doubt to unacceptable errors. Consequently a modeling strategy is being developed and leads also to improve the conceptual model of the hydrosystem. Lumped models mainly based on tritium time series allow the whole hydrosystem to be modeled combining in series: an exponential model (superficial aquifers of the "Gavot Plateau Complex"), a dispersive model (Gavot Plateau interstratified complex) and a piston flow model (sand and gravel from the Kame terraces) respectively 8, 60 and 2.5 years of mean transit time. These models provide insight on the governing parameters for the whole mineral aquifer. They help improving the current conceptual model and are to be improved with other environmental tracers such as CFC, SF6. A deterministic approach (distributed model; flow and transport) is performed at the scale of the terminal complex. The geometry of the system is quite well known from drill holes and the aquifer properties from data processing of hydraulic heads and pumping tests interpretation. A multidisciplinary approach (hydrodynamic, hydrochemistry, geology, isotopes) for the recharge area (Gavot Plateau Complex) aims to provide better constraint for the upstream boundary of distributed model. More, perfect tracer modeling approach highly constrains fitting of this distributed model. The result is a high resolution conceptual model leading to a future operational management tool of the aquifer.

Purification of polymorphic components of complex genomes

DOEpatents

Stodolsky, M.

1991-07-16

A method is disclosed for processing related subject and reference macromolecule populations composed of complementary strands into their respective subject and reference populations of representative fragments and effectuating purification of unique polymorphic subject fragments. 1 figure.

Phospholipase D and phosphatidic acid in plant defence response: from protein–protein and lipid–protein interactions to hormone signalling

PubMed Central

Zhao, Jian

2015-01-01

Phospholipase Ds (PLDs) and PLD-derived phosphatidic acids (PAs) play vital roles in plant hormonal and environmental responses and various cellular dynamics. Recent studies have further expanded the functions of PLDs and PAs into plant–microbe interaction. The molecular diversities and redundant functions make PLD–PA an important signalling complex regulating lipid metabolism, cytoskeleton dynamics, vesicle trafficking, and hormonal signalling in plant defence through protein–protein and protein–lipid interactions or hormone signalling. Different PLD–PA signalling complexes and their targets have emerged as fast-growing research topics for understanding their numerous but not yet established roles in modifying pathogen perception, signal transduction, and downstream defence responses. Meanwhile, advanced lipidomics tools have allowed researchers to reveal further the mechanisms of PLD–PA signalling complexes in regulating lipid metabolism and signalling, and their impacts on jasmonic acid/oxylipins, salicylic acid, and other hormone signalling pathways that essentially mediate plant defence responses. This review attempts to summarize the progress made in spatial and temporal PLD/PA signalling as well as PLD/PA-mediated modification of plant defence. It presents an in-depth discussion on the functions and potential mechanisms of PLD–PA complexes in regulating actin filament/microtubule cytoskeleton, vesicle trafficking, and hormonal signalling, and in influencing lipid metabolism-derived metabolites as critical signalling components in plant defence responses. The discussion puts PLD–PA in a broader context in order to guide future research. PMID:25680793

Ring-resonator-integrated tunable external cavity laser employing EAM and SOA.

PubMed

Yoon, Ki-Hong; Kwon, O-Kyun; Kim, Ki Soo; Choi, Byung-Seok; Oh, Su Hwan; Kim, Hyun Su; Sim, Jae-Sik; Kim, Chul Soo

2011-12-05

We propose and demonstrate a tunable external cavity laser (ECL) composed of a polymer Bragg reflector (PBR) and integrated gain chip with gain, a ring resonator, an electro-absorption modulator (EAM), and a semiconductor optical amplifier (SOA). The cavity of the laser is composed of the PBR, gain, and ring resonator. The ring resonator reflects the predetermined wavelengths into the gain region and transmits the output signal into integrated devices such as the EAM and SOA. The output wavelength of the tunable laser is discretely tuned in steps of about 0.8 nm through the thermal-optic effect of the PBR and predetermined mode spacing of the ring resonator.

Aggregated Indexing of Biomedical Time Series Data

PubMed Central

Woodbridge, Jonathan; Mortazavi, Bobak; Sarrafzadeh, Majid; Bui, Alex A.T.

2016-01-01

Remote and wearable medical sensing has the potential to create very large and high dimensional datasets. Medical time series databases must be able to efficiently store, index, and mine these datasets to enable medical professionals to effectively analyze data collected from their patients. Conventional high dimensional indexing methods are a two stage process. First, a superset of the true matches is efficiently extracted from the database. Second, supersets are pruned by comparing each of their objects to the query object and rejecting any objects falling outside a predetermined radius. This pruning stage heavily dominates the computational complexity of most conventional search algorithms. Therefore, indexing algorithms can be significantly improved by reducing the amount of pruning. This paper presents an online algorithm to aggregate biomedical times series data to significantly reduce the search space (index size) without compromising the quality of search results. This algorithm is built on the observation that biomedical time series signals are composed of cyclical and often similar patterns. This algorithm takes in a stream of segments and groups them to highly concentrated collections. Locality Sensitive Hashing (LSH) is used to reduce the overall complexity of the algorithm, allowing it to run online. The output of this aggregation is used to populate an index. The proposed algorithm yields logarithmic growth of the index (with respect to the total number of objects) while keeping sensitivity and specificity simultaneously above 98%. Both memory and runtime complexities of time series search are improved when using aggregated indexes. In addition, data mining tasks, such as clustering, exhibit runtimes that are orders of magnitudes faster when run on aggregated indexes. PMID:27617298

Music-induced emotions can be predicted from a combination of brain activity and acoustic features.

PubMed

Daly, Ian; Williams, Duncan; Hallowell, James; Hwang, Faustina; Kirke, Alexis; Malik, Asad; Weaver, James; Miranda, Eduardo; Nasuto, Slawomir J

2015-12-01

It is widely acknowledged that music can communicate and induce a wide range of emotions in the listener. However, music is a highly-complex audio signal composed of a wide range of complex time- and frequency-varying components. Additionally, music-induced emotions are known to differ greatly between listeners. Therefore, it is not immediately clear what emotions will be induced in a given individual by a piece of music. We attempt to predict the music-induced emotional response in a listener by measuring the activity in the listeners electroencephalogram (EEG). We combine these measures with acoustic descriptors of the music, an approach that allows us to consider music as a complex set of time-varying acoustic features, independently of any specific music theory. Regression models are found which allow us to predict the music-induced emotions of our participants with a correlation between the actual and predicted responses of up to r=0.234,p<0.001. This regression fit suggests that over 20% of the variance of the participant's music induced emotions can be predicted by their neural activity and the properties of the music. Given the large amount of noise, non-stationarity, and non-linearity in both EEG and music, this is an encouraging result. Additionally, the combination of measures of brain activity and acoustic features describing the music played to our participants allows us to predict music-induced emotions with significantly higher accuracies than either feature type alone (p<0.01). Copyright © 2015 Elsevier Inc. All rights reserved.

Chansporter complexes in cell signaling.

PubMed

Abbott, Geoffrey W

2017-09-01

Ion channels facilitate diffusion of ions across cell membranes for such diverse purposes as neuronal signaling, muscular contraction, and fluid homeostasis. Solute transporters often utilize ionic gradients to move aqueous solutes up their concentration gradient, also fulfilling a wide variety of tasks. Recently, an increasing number of ion channel-transporter ('chansporter') complexes have been discovered. Chansporter complex formation may overcome what could otherwise be considerable spatial barriers to rapid signal integration and feedback between channels and transporters, the ions and other substrates they transport, and environmental factors to which they must respond. Here, current knowledge in this field is summarized, covering both heterologous expression structure/function findings and potential mechanisms by which chansporter complexes fulfill contrasting roles in cell signaling in vivo. © 2017 Federation of European Biochemical Societies.

Processing of simple and complex acoustic signals in a tonotopically organized ear

PubMed Central

Hummel, Jennifer; Wolf, Konstantin; Kössl, Manfred; Nowotny, Manuela

2014-01-01

Processing of complex signals in the hearing organ remains poorly understood. This paper aims to contribute to this topic by presenting investigations on the mechanical and neuronal response of the hearing organ of the tropical bushcricket species Mecopoda elongata to simple pure tone signals as well as to the conspecific song as a complex acoustic signal. The high-frequency hearing organ of bushcrickets, the crista acustica (CA), is tonotopically tuned to frequencies between about 4 and 70 kHz. Laser Doppler vibrometer measurements revealed a strong and dominant low-frequency-induced motion of the CA when stimulated with either pure tone or complex stimuli. Consequently, the high-frequency distal area of the CA is more strongly deflected by low-frequency-induced waves than by high-frequency-induced waves. This low-frequency dominance will have strong effects on the processing of complex signals. Therefore, we additionally studied the neuronal response of the CA to native and frequency-manipulated chirps. Again, we found a dominant influence of low-frequency components within the conspecific song, indicating that the mechanical vibration pattern highly determines the neuronal response of the sensory cells. Thus, we conclude that the encoding of communication signals is modulated by ear mechanics. PMID:25339727

Design and implementation of an audio indicator

NASA Astrophysics Data System (ADS)

Zheng, Shiyong; Li, Zhao; Li, Biqing

2017-04-01

This page proposed an audio indicator which designed by using C9014, LED by operational amplifier level indicator, the decimal count/distributor of CD4017. The experimental can control audibly neon and holiday lights through the signal. Input audio signal after C9014 composed of operational amplifier for power amplifier, the adjust potentiometer extraction amplification signal input voltage CD4017 distributors make its drive to count, then connect the LED display running situation of the circuit. This simple audio indicator just use only U1 and can produce two colors LED with the audio signal tandem come pursuit of the running effect, from LED display the running of the situation takes can understand the general audio signal. The variation in the audio and the frequency of the signal and the corresponding level size. In this light can achieve jump to change, slowly, atlas, lighting four forms, used in home, hotel, discos, theater, advertising and other fields, and a wide range of USES, rU1h life in a modern society.

Mechanical signaling coordinates the embryonic heart

NASA Astrophysics Data System (ADS)

Chiou, Kevin; Rocks, Jason; Prosser, Benjamin; Discher, Dennis; Liu, Andrea

The heart is an active material which relies on robust signaling mechanisms between cells in order to produce well-timed, coordinated beats. Heart tissue is composed primarily of active heart muscle cells (cardiomyocytes) embedded in a passive extracellular matrix. During a heartbeat, cardiomyocyte contractions are coordinated across the heart to form a wavefront that propagates through the tissue to pump blood. In the adult heart, this contractile wave is coordinated via intercellular electrical signaling.Here we present theoretical and experimental evidence for mechanical coordination of embryonic heartbeats. We model cardiomyocytes as mechanically excitable Eshelby inclusions embedded in an overdamped elastic-fluid biphasic medium. For physiological parameters, this model replicates recent experimental measurements of the contractile wavefront which are not captured by electrical signaling models. We additionally challenge our model by pharmacologically blocking gap junctions, inhibiting electrical signaling between myocytes. We find that while adult hearts stop beating almost immediately after gap junctions are blocked, embryonic hearts continue beating even at significantly higher concentrations, providing strong support for a mechanical signaling mechanism.

Adhesion signals of phospholipid vesicles at an electrified interface.

PubMed

DeNardis, Nadica Ivošević; Žutić, Vera; Svetličić, Vesna; Frkanec, Ruža

2012-09-01

General adhesion behavior of phospholipid vesicles was examined in a wide range of potentials at the mercury electrode by recording time-resolved adhesion signals. It was demonstrated that adhesion-based detection is sensitive to polar headgroups in phospholipid vesicles. We identified a narrow potential window around the point of zero charge of the electrode where the interaction of polar headgroups of phosphatidylcholine vesicles with the substrate is manifested in the form of bidirectional signals. The bidirectional signal is composed of the charge flow due to the nonspecific interaction of vesicle adhesion and spreading and of the charge flow due to a specific interaction of the negatively charged electrode and the most exposed positively charged choline headgroups. These signals are expected to appear only when the electrode surface charge density is less than the surface charge density of the choline groups at the contact interface. In comparison, for the negatively charged phosphatidylserine vesicles, we identified the potential window at the mercury electrode where charge compensation takes place, and bidirectional signals were not detected.

A Baseline-Free Defect Imaging Technique in Plates Using Time Reversal of Lamb Waves

NASA Astrophysics Data System (ADS)

Hyunjo, Jeong; Sungjong, Cho; Wei, Wei

2011-06-01

We present an analytical investigation for a baseline-free imaging of a defect in plate-like structures using the time-reversal of Lamb waves. We first consider the flexural wave (A0 mode) propagation in a plate containing a defect, and reception and time reversal process of the output signal at the receiver. The received output signal is then composed of two parts: a directly propagated wave and a scattered wave from the defect. The time reversal of these waves recovers the original input signal, and produces two additional sidebands that contain the time-of-flight information on the defect location. One of the side-band signals is then extracted as a pure defect signal. A defect localization image is then constructed from a beamforming technique based on the time-frequency analysis of the side band signal for each transducer pair in a network of sensors. The simulation results show that the proposed scheme enables the accurate, baseline-free imaging of a defect.

Genome Dynamics and Evolution of the Mla (Powdery Mildew) Resistance Locus in BarleyW⃞

PubMed Central

Wei, Fusheng; Wing, Rod A.; Wise, Roger P.

2002-01-01

Genes that confer defense against pathogens often are clustered in the genome and evolve via diverse mechanisms. To evaluate the organization and content of a major defense gene complex in cereals, we determined the complete sequence of a 261-kb BAC contig from barley cv Morex that spans the Mla (powdery mildew) resistance locus. Among the 32 predicted genes on this contig, 15 are associated with plant defense responses; 6 of these are associated with defense responses to powdery mildew disease but function in different signaling pathways. The Mla region is organized as three gene-rich islands separated by two nested complexes of transposable elements and a 45-kb gene-poor region. A heterochromatic-like region is positioned directly proximal to Mla and is composed of a gene-poor core with 17 families of diverse tandem repeats that overlap a hypermethylated, but transcriptionally active, gene-dense island. Paleontology analysis of long terminal repeat retrotransposons indicates that the present Mla region evolved over a period of >7 million years through a variety of duplication, inversion, and transposon-insertion events. Sequence-based recombination estimates indicate that R genes positioned adjacent to nested long terminal repeat retrotransposons, such as Mla, do not favor recombination as a means of diversification. We present a model for the evolution of the Mla region that encompasses several emerging features of large cereal genomes. PMID:12172030

CMC determination of nonionic surfactants in protein formulations using ultrasonic resonance technology.

PubMed

Horiuchi, Shohei; Winter, Gerhard

2015-05-01

Biological products often contain surfactants as stabilizers in their formulations to avoid surface adsorption, interfacial denaturation and aggregation of the protein drug and thereby improve the overall pharmaceutical quality of the product. On the other hand, when the surfactant concentration exceeds the critical micelle concentration (CMC) in a protein formulation, protein-loaded micelles could be formed which could potentially be the cause of immunogenicity. Therefore, the actual CMC and the presence of micelles generally need to be confirmed for each protein formulation because the CMC is affected by the presence of protein and other formulation factors. In this study, the ultrasonic resonance technology (URT) was applied to determine CMC of surfactants in pharmaceutical protein solutions in comparison with surface tensiometry (TE) and dynamic light scattering (DLS). According to our results, the ultrasonic resonance technology can easily and precisely provide CMCs of surfactants in protein formulations while it is not working for protein-free formulations. This indicates that the signal we measure with ultrasonic velocity comes from complex micelles composed of surfactant and protein molecules. DLS did not provide reliable data for protein/surfactant systems. Interestingly, a protein formulation with arginine and polysorbate 20 behaved differently when studied with TE and URT allowing us to see that arginine is bound to protein and that the complex interacts with the surfactant. Copyright © 2015 Elsevier B.V. All rights reserved.

Identification of dynamin as a septin-binding protein.

PubMed

Maimaitiyiming, Maowulan; Kobayashi, Yuumi; Kumanogoh, Haruko; Nakamura, Shun; Morita, Mitsuhiro; Maekawa, Shohei

2013-02-08

Lipid rafts (detergent-resistant low-density membrane microdomain: DRM) are signal-transducing membrane platforms. In a previous study, we showed maturation-dependent localization of septin in the DRM fraction of rat brain. Mammalian septin is composed with 13-14 isoforms and these isoforms assemble to form rod-shaped hetero-oligomeric complexes. End-to-end polymerization of these complexes results in the formation of higher order structures such as filamentous sheets or bundles of filaments that restrict the fluid-like diffusion of the membrane proteins and lipids. Considering the function of septin as the membrane scaffold, elucidation of the molecular interaction of septin in DRM could be a breakthrough to understand another role of lipid rafts. In order to identify septin-binding proteins in DRM, solubilization and fractionation of septin from DRM was attempted. Several proteins were co-fractionated with septin and LC-MS/MS analysis identified one of these proteins as dynamin and Western blotting using anti-dynamin confirmed this result. Immunoprecipitation of septin11 in a crude supernatant showed co-precipitation of dynamin and dynamin fraction prepared from brain contained several septin isoforms. Within bacterially expressed septin isoforms, septin5 and septin11 bound dynamin but septin9 did not. These results suggest that some septin isoforms participate in the dynamin-related membrane dynamics. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Independent origins of neurons and synapses: insights from ctenophores

PubMed Central

Moroz, Leonid L.; Kohn, Andrea B.

2016-01-01

There is more than one way to develop neuronal complexity, and animals frequently use different molecular toolkits to achieve similar functional outcomes. Genomics and metabolomics data from basal metazoans suggest that neural signalling evolved independently in ctenophores and cnidarians/bilaterians. This polygenesis hypothesis explains the lack of pan-neuronal and pan-synaptic genes across metazoans, including remarkable examples of lineage-specific evolution of neurogenic and signalling molecules as well as synaptic components. Sponges and placozoans are two lineages without neural and muscular systems. The possibility of secondary loss of neurons and synapses in the Porifera/Placozoa clades is a highly unlikely and less parsimonious scenario. We conclude that acetylcholine, serotonin, histamine, dopamine, octopamine and gamma-aminobutyric acid (GABA) were recruited as transmitters in the neural systems in cnidarian and bilaterian lineages. By contrast, ctenophores independently evolved numerous secretory peptides, indicating extensive adaptations within the clade and suggesting that early neural systems might be peptidergic. Comparative analysis of glutamate signalling also shows numerous lineage-specific innovations, implying the extensive use of this ubiquitous metabolite and intercellular messenger over the course of convergent and parallel evolution of mechanisms of intercellular communication. Therefore: (i) we view a neuron as a functional character but not a genetic character, and (ii) any given neural system cannot be considered as a single character because it is composed of different cell lineages with distinct genealogies, origins and evolutionary histories. Thus, when reconstructing the evolution of nervous systems, we ought to start with the identification of particular cell lineages by establishing distant neural homologies or examples of convergent evolution. In a corollary of the hypothesis of the independent origins of neurons, our analyses suggest that both electrical and chemical synapses evolved more than once. PMID:26598724

Genome-wide association analysis reveals putative Alzheimer's disease susceptibility loci in addition to APOE.

PubMed

Bertram, Lars; Lange, Christoph; Mullin, Kristina; Parkinson, Michele; Hsiao, Monica; Hogan, Meghan F; Schjeide, Brit M M; Hooli, Basavaraj; Divito, Jason; Ionita, Iuliana; Jiang, Hongyu; Laird, Nan; Moscarillo, Thomas; Ohlsen, Kari L; Elliott, Kathryn; Wang, Xin; Hu-Lince, Diane; Ryder, Marie; Murphy, Amy; Wagner, Steven L; Blacker, Deborah; Becker, K David; Tanzi, Rudolph E

2008-11-01

Alzheimer's disease (AD) is a genetically complex and heterogeneous disorder. To date four genes have been established to either cause early-onset autosomal-dominant AD (APP, PSEN1, and PSEN2(1-4)) or to increase susceptibility for late-onset AD (APOE5). However, the heritability of late-onset AD is as high as 80%, (6) and much of the phenotypic variance remains unexplained to date. We performed a genome-wide association (GWA) analysis using 484,522 single-nucleotide polymorphisms (SNPs) on a large (1,376 samples from 410 families) sample of AD families of self-reported European descent. We identified five SNPs showing either significant or marginally significant genome-wide association with a multivariate phenotype combining affection status and onset age. One of these signals (p = 5.7 x 10(-14)) was elicited by SNP rs4420638 and probably reflects APOE-epsilon4, which maps 11 kb proximal (r2 = 0.78). The other four signals were tested in three additional independent AD family samples composed of nearly 2700 individuals from almost 900 families. Two of these SNPs showed significant association in the replication samples (combined p values 0.007 and 0.00002). The SNP (rs11159647, on chromosome 14q31) with the strongest association signal also showed evidence of association with the same allele in GWA data generated in an independent sample of approximately 1,400 AD cases and controls (p = 0.04). Although the precise identity of the underlying locus(i) remains elusive, our study provides compelling evidence for the existence of at least one previously undescribed AD gene that, like APOE-epsilon4, primarily acts as a modifier of onset age.

Genome-wide Association Analysis Reveals Putative Alzheimer's Disease Susceptibility Loci in Addition to APOE

PubMed Central

Bertram, Lars; Lange, Christoph; Mullin, Kristina; Parkinson, Michele; Hsiao, Monica; Hogan, Meghan F.; Schjeide, Brit M.M.; Hooli, Basavaraj; DiVito, Jason; Ionita, Iuliana; Jiang, Hongyu; Laird, Nan; Moscarillo, Thomas; Ohlsen, Kari L.; Elliott, Kathryn; Wang, Xin; Hu-Lince, Diane; Ryder, Marie; Murphy, Amy; Wagner, Steven L.; Blacker, Deborah; Becker, K. David; Tanzi, Rudolph E.

2008-01-01

Alzheimer's disease (AD) is a genetically complex and heterogeneous disorder. To date four genes have been established to either cause early-onset autosomal-dominant AD (APP, PSEN1, and PSEN21–4) or to increase susceptibility for late-onset AD (APOE5). However, the heritability of late-onset AD is as high as 80%,6 and much of the phenotypic variance remains unexplained to date. We performed a genome-wide association (GWA) analysis using 484,522 single-nucleotide polymorphisms (SNPs) on a large (1,376 samples from 410 families) sample of AD families of self-reported European descent. We identified five SNPs showing either significant or marginally significant genome-wide association with a multivariate phenotype combining affection status and onset age. One of these signals (p = 5.7 × 10−14) was elicited by SNP rs4420638 and probably reflects APOE-ɛ4, which maps 11 kb proximal (r2 = 0.78). The other four signals were tested in three additional independent AD family samples composed of nearly 2700 individuals from almost 900 families. Two of these SNPs showed significant association in the replication samples (combined p values 0.007 and 0.00002). The SNP (rs11159647, on chromosome 14q31) with the strongest association signal also showed evidence of association with the same allele in GWA data generated in an independent sample of ∼1,400 AD cases and controls (p = 0.04). Although the precise identity of the underlying locus(i) remains elusive, our study provides compelling evidence for the existence of at least one previously undescribed AD gene that, like APOE-ɛ4, primarily acts as a modifier of onset age. PMID:18976728

Activator of G Protein Signaling 8 (AGS8) Is Required for Hypoxia-induced Apoptosis of Cardiomyocytes

PubMed Central

Sato, Motohiko; Jiao, Qibin; Honda, Takashi; Kurotani, Reiko; Toyota, Eiji; Okumura, Satoshi; Takeya, Tatsuo; Minamisawa, Susumu; Lanier, Stephen M.; Ishikawa, Yoshihiro

2009-01-01

Ischemic injury of the heart is associated with activation of multiple signal transduction systems including the heterotrimeric G-protein system. Here, we report a role of the ischemia-inducible regulator of Gβγ subunit, AGS8, in survival of cardiomyocytes under hypoxia. Cultured rat neonatal cardiomyocytes (NCM) were exposed to hypoxia or hypoxia/reoxygenation following transfection of AGS8siRNA or pcDNA::AGS8. Hypoxia-induced apoptosis of NCM was completely blocked by AGS8siRNA, whereas overexpression of AGS8 increased apoptosis. AGS8 formed complexes with G-proteins and channel protein connexin 43 (CX43), which regulates the permeability of small molecules under hypoxic stress. AGS8 initiated CX43 phosphorylation in a Gβγ-dependent manner by providing a scaffold composed of Gβγ and CX43. AGS8siRNA blocked internalization of CX43 following exposure of NCM to repetitive hypoxia; however it did not influence epidermal growth factor-mediated internalization of CX43. The decreased dye flux through CX43 that occurred with hypoxic stress was also prevented by AGS8siRNA. Interestingly, the Gβγ inhibitor Gallein mimicked the effect of AGS8 knockdown on both the CX43 internalization and the changes in cell permeability elicited by hypoxic stress. These data indicate that AGS8 is required for hypoxia-induced apoptosis of NCM, and that AGS8-Gβγ signal input increased the sensitivity of cells to hypoxic stress by influencing CX43 regulation and associated cell permeability. Under hypoxic stress, this unrecognized response program plays a critical role in the fate of NCM. PMID:19723622

Effects of off-resonance spins on the performance of the modulated gradient spin echo sequence.

PubMed

Serša, Igor; Bajd, Franci; Mohorič, Aleš

2016-09-01

Translational molecular dynamics in various materials can also be studied by diffusion spectra. These can be measured by a constant gradient variant of the modulated gradient spin echo (MGSE) sequence which is composed of a CPMG RF pulse train superimposed to a constant magnetic field gradient. The application of the RF train makes the effective gradient oscillating thus enabling measurements of diffusion spectra in a wide range of frequencies. However, seemingly straightforward implementation of the MGSE sequence proved to be complicated and can give overestimated results for diffusion if not interpreted correctly. In this study, unrestricted diffusion in water and other characteristic materials was analyzed by the MGSE sequence in the frequency range 50-3000Hz using a 6T/m diffusion probe. First, it was shown that the MGSE echo train acquired from the entire sample decays faster than the train acquired only from a narrow band at zero frequency of the sample. Then, it was shown that the decay rate is dependent on the band's off-resonance characterized by the ratio Δω0/ω1 and that with higher off-resonances the decay is faster. The faster decay therefore corresponds to a higher diffusion coefficient if the diffusion is calculated using standard Stejskal-Tanner formula. The result can be explained by complex coherence pathways contributing to the MGSE echo signals when |Δω0|/ω1>0. In a magnetic field gradient, all the pathways are more diffusion attenuated than the direct coherence pathway and therefore decay faster, which leads to an overestimation of the diffusion coefficient. A solution to this problem was found in an efficient off-resonance signal reduction by using only zero frequency filtered MGSE echo train signals. Copyright © 2016 Elsevier Inc. All rights reserved.

Establishment of spatial pattern.

PubMed

Slack, Jonathan

2014-01-01

An overview and perspective are presented of mechanisms for the development of spatial pattern in animal embryos. It is intended both for new entrants to developmental biology and for specialists in other fields, with only a basic knowledge of animal life cycles being required. The first event of pattern formation is normally the localization of a cytoplasmic determinant in the egg, either during oogenesis or post-fertilization. Following cleavage to a multicellular stage, some cells contain the determinant and others do not. The determinant confers a specific developmental pathway on the cells that contain it, often making them the source of the first extracellular signal, or inducing factor. Inducing factors often form concentration gradients to which cells respond by up or downregulating genes at various concentration thresholds. This enables an initial situation consisting of two cell states (with or without the determinant) to generate a multistate pattern. Multiple rounds of gradient signaling, interspersed with phases of morphogenetic movements, can generate a complex pattern using a small number of signals and responding genes. Development proceeds in a hierarchical manner, with broad body subdivisions being specified initially, and becoming successively subdivided to give individual organs and tissues composed of multiple cell types in a characteristic arrangement. Double gradient models can account for embryonic regulation, whereby a similarly proportioned body pattern is formed following removal of material. Processes that are involved at the later stages include the formation of repeating structures by the combination of an oscillator with a gradient, and the formation of tissues with one cell type scattered in a background of another through a process called lateral inhibition. This set of processes make up a 'developmental toolkit' which can be deployed in various sequences and combinations to generate a very wide variety of structures and cell types. © 2014 Wiley Periodicals, Inc.

Hydrogen release reactions of Al-based complex hydrides enhanced by vibrational dynamics and valences of metal cations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sato, T.; Ramirez-Cuesta, Anibal J.; Daemen, Luke L.

2016-08-31

Hydrogen release from Al-based complex hydrides composed of metal cation(s) and [AlH4] – was investigated using inelastic neutron scattering viewed from vibrational dynamics. Here, the hydrogen release followed the softening of translational and [AlH4] – librational modes, which was enhanced by vibrational dynamics and the valence(s) of the metal cation(s).

Complex Dynamic Scene Perception: Effects of Attentional Set on Perceiving Single and Multiple Event Types

ERIC Educational Resources Information Center

Sanocki, Thomas; Sulman, Noah

2013-01-01

Three experiments measured the efficiency of monitoring complex scenes composed of changing objects, or events. All events lasted about 4 s, but in a given block of trials, could be of a single type (single task) or of multiple types (multitask, with a total of four event types). Overall accuracy of detecting target events amid distractors was…

A-Kinase Anchoring Proteins: From protein complexes to physiology and disease

PubMed Central

Carnegie, Graeme K.; Means, Christopher K.; Scott, John D.

2009-01-01

Protein scaffold complexes are a key mechanism by which a common signaling pathway can serve many different functions. Sequestering a signaling enzyme to a specific subcellular environment not only ensures that the enzyme is near its relevant targets, but also segregates this activity to prevent indiscriminate phosphorylation of other substrates. One family of diverse, well-studied scaffolding proteins are the A-kinase anchoring proteins (AKAPs). These anchoring proteins form multi-protein complexes that integrate cAMP signaling with other pathways and signaling events. In this review we focus on recent advances in the elucidation of AKAP function. PMID:19319965

A-kinase anchoring proteins: from protein complexes to physiology and disease.

PubMed

Carnegie, Graeme K; Means, Christopher K; Scott, John D

2009-04-01

Protein scaffold complexes are a key mechanism by which a common signaling pathway can serve many different functions. Sequestering a signaling enzyme to a specific subcellular environment not only ensures that the enzyme is near its relevant targets, but also segregates this activity to prevent indiscriminate phosphorylation of other substrates. One family of diverse, well-studied scaffolding proteins are the A-kinase anchoring proteins (AKAPs). These anchoring proteins form multi-protein complexes that integrate cAMP signaling with other pathways and signaling events. In this review, we focus on recent advances in the elucidation of AKAP function.

Information Theory Applied to Dolphin Whistle Vocalizations with Possible Application to SETI Signals

NASA Astrophysics Data System (ADS)

Doyle, Laurance R.; McCowan, Brenda; Hanser, Sean F.

2002-01-01

Information theory allows a quantification of the complexity of a given signaling system. We are applying information theory to dolphin whistle vocalizations, humpback whale songs, squirrel monkey chuck calls, and several other animal communication systems' in order to develop a quantitative and objective way to compare inter species communication systems' complexity. Once signaling units have been correctly classified the communication system must obey certain statistical distributions in order to contain complexity whether it is human languages, dolphin whistle vocalizations, or even a system of communication signals received from an extraterrestrial source.

Auditory sensitivity of seals and sea lions in complex listening scenarios.

PubMed

Cunningham, Kane A; Southall, Brandon L; Reichmuth, Colleen

2014-12-01

Standard audiometric data, such as audiograms and critical ratios, are often used to inform marine mammal noise-exposure criteria. However, these measurements are obtained using simple, artificial stimuli-i.e., pure tones and flat-spectrum noise-while natural sounds typically have more complex structure. In this study, detection thresholds for complex signals were measured in (I) quiet and (II) masked conditions for one California sea lion (Zalophus californianus) and one harbor seal (Phoca vitulina). In Experiment I, detection thresholds in quiet conditions were obtained for complex signals designed to isolate three common features of natural sounds: Frequency modulation, amplitude modulation, and harmonic structure. In Experiment II, detection thresholds were obtained for the same complex signals embedded in two types of masking noise: Synthetic flat-spectrum noise and recorded shipping noise. To evaluate how accurately standard hearing data predict detection of complex sounds, the results of Experiments I and II were compared to predictions based on subject audiograms and critical ratios combined with a basic hearing model. Both subjects exhibited greater-than-predicted sensitivity to harmonic signals in quiet and masked conditions, as well as to frequency-modulated signals in masked conditions. These differences indicate that the complex features of naturally occurring sounds enhance detectability relative to simple stimuli.

ATM-Dependent Phosphorylation of All Three Members of the MRN Complex: From Sensor to Adaptor

PubMed Central

Lavin, Martin F.; Kozlov, Sergei; Gatei, Magtouf; Kijas, Amanda W.

2015-01-01

The recognition, signalling and repair of DNA double strand breaks (DSB) involves the participation of a multitude of proteins and post-translational events that ensure maintenance of genome integrity. Amongst the proteins involved are several which when mutated give rise to genetic disorders characterised by chromosomal abnormalities, cancer predisposition, neurodegeneration and other pathologies. ATM (mutated in ataxia-telangiectasia (A-T) and members of the Mre11/Rad50/Nbs1 (MRN complex) play key roles in this process. The MRN complex rapidly recognises and locates to DNA DSB where it acts to recruit and assist in ATM activation. ATM, in the company of several other DNA damage response proteins, in turn phosphorylates all three members of the MRN complex to initiate downstream signalling. While ATM has hundreds of substrates, members of the MRN complex play a pivotal role in mediating the downstream signalling events that give rise to cell cycle control, DNA repair and ultimately cell survival or apoptosis. Here we focus on the interplay between ATM and the MRN complex in initiating signaling of breaks and more specifically on the adaptor role of the MRN complex in mediating ATM signalling to downstream substrates to control different cellular processes. PMID:26512707

Automatic QRS complex detection using two-level convolutional neural network.

PubMed

Xiang, Yande; Lin, Zhitao; Meng, Jianyi

2018-01-29

The QRS complex is the most noticeable feature in the electrocardiogram (ECG) signal, therefore, its detection is critical for ECG signal analysis. The existing detection methods largely depend on hand-crafted manual features and parameters, which may introduce significant computational complexity, especially in the transform domains. In addition, fixed features and parameters are not suitable for detecting various kinds of QRS complexes under different circumstances. In this study, based on 1-D convolutional neural network (CNN), an accurate method for QRS complex detection is proposed. The CNN consists of object-level and part-level CNNs for extracting different grained ECG morphological features automatically. All the extracted morphological features are used by multi-layer perceptron (MLP) for QRS complex detection. Additionally, a simple ECG signal preprocessing technique which only contains difference operation in temporal domain is adopted. Based on the MIT-BIH arrhythmia (MIT-BIH-AR) database, the proposed detection method achieves overall sensitivity Sen = 99.77%, positive predictivity rate PPR = 99.91%, and detection error rate DER = 0.32%. In addition, the performance variation is performed according to different signal-to-noise ratio (SNR) values. An automatic QRS detection method using two-level 1-D CNN and simple signal preprocessing technique is proposed for QRS complex detection. Compared with the state-of-the-art QRS complex detection approaches, experimental results show that the proposed method acquires comparable accuracy.

Aiding the Detection of QRS Complex in ECG Signals by Detecting S Peaks Independently.

PubMed

Sabherwal, Pooja; Singh, Latika; Agrawal, Monika

2018-03-30

In this paper, a novel algorithm for the accurate detection of QRS complex by combining the independent detection of R and S peaks, using fusion algorithm is proposed. R peak detection has been extensively studied and is being used to detect the QRS complex. Whereas, S peaks, which is also part of QRS complex can be independently detected to aid the detection of QRS complex. In this paper, we suggest a method to first estimate S peak from raw ECG signal and then use them to aid the detection of QRS complex. The amplitude of S peak in ECG signal is relatively weak than corresponding R peak, which is traditionally used for the detection of QRS complex, therefore, an appropriate digital filter is designed to enhance the S peaks. These enhanced S peaks are then detected by adaptive thresholding. The algorithm is validated on all the signals of MIT-BIH arrhythmia database and noise stress database taken from physionet.org. The algorithm performs reasonably well even for the signals highly corrupted by noise. The algorithm performance is confirmed by sensitivity and positive predictivity of 99.99% and the detection accuracy of 99.98% for QRS complex detection. The number of false positives and false negatives resulted while analysis has been drastically reduced to 80 and 42 against the 98 and 84 the best results reported so far.

Fabrication of the tetrathiafulvalene–2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane charge transfer complex with high crystallinity by eutectic melting method

NASA Astrophysics Data System (ADS)

Kim, Jueun; Kang, Youngjong; Lee, Jaejong

2018-06-01

We show that high crystallinity and charge transporting gain can be obtained in a noble donor–acceptor system (CT complex) composed of organic complex: tetrathiafulvalene–2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (TTF–F4TCNQ). The complex is small-gap organic metallic or semiconductor (less than 1 eV), and we predict having a high conductivity. We perform an approach to fabricate organic CT complex with high crystallinity by eutectic melting method. Our process is simple and shows crystal growth with improved crystallinity when combined with soft-lithography.

Dynamic Primitives of Motor Behavior

PubMed Central

Hogan, Neville; Sternad, Dagmar

2013-01-01

We present in outline a theory of sensorimotor control based on dynamic primitives, which we define as attractors. To account for the broad class of human interactive behaviors—especially tool use—we propose three distinct primitives: submovements, oscillations and mechanical impedances, the latter necessary for interaction with objects. Due to fundamental features of the neuromuscular system, most notably its slow response, we argue that encoding in terms of parameterized primitives may be an essential simplification required for learning, performance, and retention of complex skills. Primitives may simultaneously and sequentially be combined to produce observable forces and motions. This may be achieved by defining a virtual trajectory composed of submovements and/or oscillations interacting with impedances. Identifying primitives requires care: in principle, overlapping submovements would be sufficient to compose all observed movements but biological evidence shows that oscillations are a distinct primitive. Conversely, we suggest that kinematic synergies, frequently discussed as primitives of complex actions, may be an emergent consequence of neuromuscular impedance. To illustrate how these dynamic primitives may account for complex actions, we briefly review three types of interactive behaviors: constrained motion, impact tasks, and manipulation of dynamic objects. PMID:23124919

Oxygen tolerance of an in silico-designed bioinspired hydrogen-evolving catalyst in water.

PubMed

Sit, Patrick H-L; Car, Roberto; Cohen, Morrel H; Selloni, Annabella

2013-02-05

Certain bacterial enzymes, the diiron hydrogenases, have turnover numbers for hydrogen production from water as large as 10(4)/s. Their much smaller common active site, composed of earth-abundant materials, has a structure that is an attractive starting point for the design of a practical catalyst for electrocatalytic or solar photocatalytic hydrogen production from water. In earlier work, our group has reported the computational design of [FeFe](P)/FeS(2), a hydrogenase-inspired catalyst/electrode complex, which is efficient and stable throughout the production cycle. However, the diiron hydrogenases are highly sensitive to ambient oxygen by a mechanism not yet understood in detail. An issue critical for practical use of [FeFe](P)/FeS(2) is whether this catalyst/electrode complex is tolerant to the ambient oxygen. We report demonstration by ab initio simulations that the complex is indeed tolerant to dissolved oxygen over timescales long enough for practical application, reducing it efficiently. This promising hydrogen-producing catalyst, composed of earth-abundant materials and with a diffusion-limited rate in acidified water, is efficient as well as oxygen tolerant.

Oxygen tolerance of an in silico-designed bioinspired hydrogen-evolving catalyst in water

PubMed Central

Sit, Patrick H.-L.; Car, Roberto; Cohen, Morrel H.; Selloni, Annabella

2013-01-01

Certain bacterial enzymes, the diiron hydrogenases, have turnover numbers for hydrogen production from water as large as 104/s. Their much smaller common active site, composed of earth-abundant materials, has a structure that is an attractive starting point for the design of a practical catalyst for electrocatalytic or solar photocatalytic hydrogen production from water. In earlier work, our group has reported the computational design of [FeFe]P/FeS2, a hydrogenase-inspired catalyst/electrode complex, which is efficient and stable throughout the production cycle. However, the diiron hydrogenases are highly sensitive to ambient oxygen by a mechanism not yet understood in detail. An issue critical for practical use of [FeFe]P/FeS2 is whether this catalyst/electrode complex is tolerant to the ambient oxygen. We report demonstration by ab initio simulations that the complex is indeed tolerant to dissolved oxygen over timescales long enough for practical application, reducing it efficiently. This promising hydrogen-producing catalyst, composed of earth-abundant materials and with a diffusion-limited rate in acidified water, is efficient as well as oxygen tolerant. PMID:23341607

Fault severity assessment for rolling element bearings using the Lempel-Ziv complexity and continuous wavelet transform

NASA Astrophysics Data System (ADS)

Hong, Hoonbin; Liang, Ming

2009-02-01

This paper proposes a new version of the Lempel-Ziv complexity as a bearing fault (single point) severity measure based on the continuous wavelet transform (CWT) results, and attempts to address the issues present in the current version of the Lempel-Ziv complexity measure. To establish the relationship between the Lempel-Ziv complexity and bearing fault severity, an analytical model for a single-point defective bearing is adopted and the factors contributing to the complexity value are explained. To avoid the ambiguity between fault and noise, the Lempel-Ziv complexity is jointly applied with the CWT. The CWT is used to identify the best scale where the fault resides and eliminate the interferences of noise and irrelevant signal components as much as possible. Then, the Lempel-Ziv complexity values are calculated for both the envelope and high-frequency carrier signal obtained from wavelet coefficients at the best scale level. As the noise and other un-related signal components have been largely removed, the Lempel-Ziv complexity value will be mostly contributed by the bearing system and hence can be reliably used as a bearing fault measure. The applications to the bearing inner- and outer-race fault signals have demonstrated that the revised Lempel-Ziv complexity can effectively measure the severity of both inner- and outer-race faults. Since the complexity values are not dependent on the magnitude of the measured signal, the proposed method is less sensitive to the data sets measured under different data acquisition conditions. In addition, as the normalized complexity values are bounded between zero and one, it is convenient to observe the fault growing trend by examining the Lempel-Ziv complexity.

Development of nanoscale structure in LAT-based signaling complexes

PubMed Central

2016-01-01

ABSTRACT The adapter molecule linker for activation of T cells (LAT) plays a crucial role in forming signaling complexes induced by stimulation of the T cell receptor (TCR). These multi-molecular complexes are dynamic structures that activate highly regulated signaling pathways. Previously, we have demonstrated nanoscale structure in LAT-based complexes where the adapter SLP-76 (also known as LCP2) localizes to the periphery of LAT clusters. In this study, we show that initially LAT and SLP-76 are randomly dispersed throughout the clusters that form upon TCR engagement. The segregation of LAT and SLP-76 develops near the end of the spreading process. The local concentration of LAT also increases at the same time. Both changes require TCR activation and an intact actin cytoskeleton. These results demonstrate that the nanoscale organization of LAT-based signaling complexes is dynamic and indicates that different kinds of LAT-based complexes appear at different times during T cell activation. PMID:27875277

Annealing effects on hydrogenated diamond NOR logic circuits

NASA Astrophysics Data System (ADS)

Liu, J. W.; Oosato, H.; Liao, M. Y.; Imura, M.; Watanabe, E.; Koide, Y.

2018-04-01

Here, hydrogenated diamond (H-diamond) NOR logic circuits composed of two p-type enhancement-mode (E-mode) metal-oxide-semiconductor field-effect-transistors (MOSFETs) and a load resistor are fabricated and characterized. The fabrication process and the annealing effect on the electrical properties of the NOR logic circuit are demonstrated. There are distinct logical characteristics for the as-received and 300 °C annealed NOR logic circuits. When one or both input voltages for the E-mode MOSFETs are -10.0 V and "high" signals, output voltages respond 0 V and "low" signals. Instead, when both input voltages are 0 V and "low" signals, output voltage responds -10.0 V and a "high" signal. After annealing at 400 °C, the NOR logical characteristics are damaged, which is possibly attributed to the degradation of the H-diamond MOSFETs.

Experimental investigation of polarization insensitivity and cascadability with semiconductor optical amplifier-based differential phase-shift keyed wavelength converter

NASA Astrophysics Data System (ADS)

Mao, Yaya; Wu, Chongqing; Liu, Bo; Ullah, Rahat; Tian, Feng

2017-12-01

We experimentally investigate the polarization insensitivity and cascadability of an all-optical wavelength converter for differential phase-shift keyed (DPSK) signals for the first time. The proposed wavelength converter is composed of a one-bit delay interferometer demodulation stage followed by a single semiconductor optical amplifier. The impact of input DPSK signal polarization fluctuation on receiver sensitivity for the converted signal is carried out. It is found that this scheme is almost insensitive to the state of polarization of the input DPSK signal. Furthermore, the cascadability of the converter is demonstrated in a two-path recirculating loop. Error-free transmission is achieved with 20 stage cascaded wavelength conversions over 2800 km, where the power penalty is <3.4 dB at bit error rate of 10-9.

Presence of Tube isoforms in Litopenaeus vannamei suggests various regulatory patterns of signal transduction in invertebrate NF-κB pathway.

PubMed

Li, Chaozheng; Chen, Yixiao; Weng, Shaoping; Li, Sedong; Zuo, Hongliang; Yu, Xiaoqiang; Li, Haoyang; He, Jianguo; Xu, Xiaopeng

2014-02-01

The toll-like receptor (TLR)/NF-κB signaling pathways play critical roles in the innate immune system. The intracellular signal transduction of most TLR pathways in invertebrate cells is triggered by formation of a heterotrimeric complex composed of MyD88, Tube and Pelle. In this study, we identified a Litopenaeus vannamei Pelle (LvPelle) and an isoform of L. vannamei Tube (LvTube) designated as LvTube-1. The interactions among LvPelle, LvTube/LvTube-1 and LvMyD88/LvMyD88-1 were elucidated and their functions during pathogen infections were investigated. Knockdowns of LvPelle and LvTube/LvTube-1 using RNAi strategy led to higher mortalities of shrimps during Vibrio parahemolyticus infection, and could reduce the genome copy number of white spot syndrome virus (WSSV) in the infected muscle tissue but did not affect the mortality caused by WSSV infection. The effects of LvPelle and LvTube/LvTube-1 on promoters containing NF-κB binding motifs were analyzed by dual-luciferase reporter assays and the results demonstrated that LvTube-1 could activate the NF-κB activity to significantly higher level than LvTube did. Moreover, tissue distributions of LvTube and LvTube-1 mRNAs and their expression profiles during pathogen and immune stimulant challenges were different, indicating that they could play different roles in immune responses. This is the first report of Tube isoforms in invertebrates. Together with our previous study on LvMyD88 isoforms, our results suggest that various isoforms of adaptor components may be involved in various regulatory patterns of signal transduction in invertebrate TLR/NF-κB pathway and this could be a strategy adopted by invertebrates to modulate immune responses. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cell cycle control, checkpoint mechanisms, and genotoxic stress.

PubMed Central

Shackelford, R E; Kaufmann, W K; Paules, R S

1999-01-01

The ability of cells to maintain genomic integrity is vital for cell survival and proliferation. Lack of fidelity in DNA replication and maintenance can result in deleterious mutations leading to cell death or, in multicellular organisms, cancer. The purpose of this review is to discuss the known signal transduction pathways that regulate cell cycle progression and the mechanisms cells employ to insure DNA stability in the face of genotoxic stress. In particular, we focus on mammalian cell cycle checkpoint functions, their role in maintaining DNA stability during the cell cycle following exposure to genotoxic agents, and the gene products that act in checkpoint function signal transduction cascades. Key transitions in the cell cycle are regulated by the activities of various protein kinase complexes composed of cyclin and cyclin-dependent kinase (Cdk) molecules. Surveillance control mechanisms that check to ensure proper completion of early events and cellular integrity before initiation of subsequent events in cell cycle progression are referred to as cell cycle checkpoints and can generate a transient delay that provides the cell more time to repair damage before progressing to the next phase of the cycle. A variety of cellular responses are elicited that function in checkpoint signaling to inhibit cyclin/Cdk activities. These responses include the p53-dependent and p53-independent induction of Cdk inhibitors and the p53-independent inhibitory phosphorylation of Cdk molecules themselves. Eliciting proper G1, S, and G2 checkpoint responses to double-strand DNA breaks requires the function of the Ataxia telangiectasia mutated gene product. Several human heritable cancer-prone syndromes known to alter DNA stability have been found to have defects in checkpoint surveillance pathways. Exposures to several common sources of genotoxic stress, including oxidative stress, ionizing radiation, UV radiation, and the genotoxic compound benzo[a]pyrene, elicit cell cycle checkpoint responses that show both similarities and differences in their molecular signaling. Images Figure 3 PMID:10229703

The Composer's Program Note for Newly Written Classical Music: Content and Intentions.

PubMed

Blom, Diana M; Bennett, Dawn; Stevenson, Ian

2016-01-01

In concerts of western classical music the provision of a program note is a widespread practice dating back to the 18th century and still commonly in use. Program notes tend to inform listeners and performers about historical context, composer biographical details, and compositional thinking. However, the scant program note research conducted to date reveals that program notes may not foster understanding or enhance listener enjoyment as previously assumed. In the case of canonic works, performers and listeners may already be familiar with much of the program note information. This is not so in the case of newly composed works, which formed the basis of the exploratory study reported here. This article reports the views of 17 living contemporary composers on their writing of program notes for their own works. In particular, the study sought to understand the intended recipient, role and the content of composer-written program notes. Participating composers identified three main roles for their program notes: to shape a performer's interpretation of the work; to guide, engage or direct the listener and/or performer; and as collaborative mode of communication between the composer, performer, and listener. For some composers, this collaboration was intended to result in "performative listening" in which listeners were actively engaged in bringing each composition to life. This was also described as a form of empathy that results in the co-construction of the musical experience. Overall, composers avoided giving too much personal information and they provided performers with more structural information. However, composers did not agree on whether the same information should be provided to both performers and listeners. Composers' responses problematize the view of a program note as a simple statement from writer to recipient, indicating instead a more complex set of relations at play between composer, performer, listener, and the work itself. These relations are illustrated in a model. There are implications for program note writers and readers, and for educators. Future research might seek to enhance understanding of program notes, including whether the written program note is the most effective format for communications about music.

Generalized sample entropy analysis for traffic signals based on similarity measure

NASA Astrophysics Data System (ADS)

Shang, Du; Xu, Mengjia; Shang, Pengjian

2017-05-01

Sample entropy is a prevailing method used to quantify the complexity of a time series. In this paper a modified method of generalized sample entropy and surrogate data analysis is proposed as a new measure to assess the complexity of a complex dynamical system such as traffic signals. The method based on similarity distance presents a different way of signals patterns match showing distinct behaviors of complexity. Simulations are conducted over synthetic data and traffic signals for providing the comparative study, which is provided to show the power of the new method. Compared with previous sample entropy and surrogate data analysis, the new method has two main advantages. The first one is that it overcomes the limitation about the relationship between the dimension parameter and the length of series. The second one is that the modified sample entropy functions can be used to quantitatively distinguish time series from different complex systems by the similar measure.

Self-reduction of a copper complex MOD ink for inkjet printing conductive patterns on plastics.

PubMed

Farraj, Yousef; Grouchko, Michael; Magdassi, Shlomo

2015-01-31

Highly conductive copper patterns on low-cost flexible substrates are obtained by inkjet printing a metal complex based ink. Upon heating the ink, the soluble complex, which is composed of copper formate and 2-amino-2-methyl-1-propanol, decomposes under nitrogen at 140 °C and is converted to pure metallic copper. The decomposition process of the complex is investigated and a suggested mechanism is presented. The ink is stable in air for prolonged periods, with no sedimentation or oxidation problems, which are usually encountered in copper nanoparticle based inks.

Mutations in the Katnb1 gene cause left-right asymmetry and heart defects.

PubMed

Furtado, Milena B; Merriner, D Jo; Berger, Silke; Rhodes, Danielle; Jamsai, Duangporn; O'Bryan, Moira K

2017-12-01

The microtubule-severing protein complex katanin is composed two subunits, the ATPase subunit, KATNA1, and the noncatalytic regulatory subunit, KATNB1. Recently, the Katnb1 gene has been linked to infertility, regulation of centriole and cilia formation in fish and mammals, as well as neocortical brain development. KATNB1 protein is expressed in germ cells in humans and mouse, mitotic/meiotic spindles and cilia, although the full expression pattern of the Katnb1 gene has not been described. Using a knockin-knockout mouse model of Katnb1 dysfunction we demonstrate that Katnb1 is ubiquitously expressed during embryonic development, although a stronger expression is seen in the crown cells of the gastrulation organizer, the murine node. Furthermore, null and hypomorphic Katnb1 gene mutations show a novel correlation between Katnb1 dysregulation and the development of impaired left-right signaling, including cardiac malformations. Katanin function is a critical regulator of heart development in mice. These findings are potentially relevant to human cardiac development. Developmental Dynamics 246:1027-1035, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Transcription control and neuronal differentiation by agents that activate the LXR nuclear receptor family.

PubMed

Schmidt, A; Vogel, R; Holloway, M K; Rutledge, S J; Friedman, O; Yang, Z; Rodan, G A; Friedman, E

1999-09-10

LXR and PPAR receptors belong to the nuclear receptor superfamily of transcriptional activating factors. Using ligand-dependent transcription assays, we found that 5-tetradecyloxy-2-furancarboxylic acid (TOFA) transactivates chimeric receptors composed of the glucocorticoid receptor DNA binding domain and the ligand binding regions of PPARalpha, PPARbeta (NUC-1) and LXRbeta (NER) receptors. In the same assays, ligands for PPARs (oleic acid, WY-14643 and L-631,033) and LXRs (hydroxycholesterols) maintain their respective receptor selectivity. TOFA and hydroxycholesterols also stimulate transcription from a minimal fibrinogen promoter that is under the control of AP-1 or NF-kappaB transcription factor binding sites. In addition to their effects on transcription, these LXRbeta activators induce neuronal differentiation in rat pheochromocytoma cells. TOFA and the natural LXR agonist, 22 (R)-hydroxycholesterol, stimulate neurite outgrowth in 55 and 28% of cells, respectively. No neurite outgrowth was induced by the related 22(S)-hydroxycholesterol, which does not activate the LXR family. These results suggest that the hydroxycholesterol signaling pathway has a complex effect on transcription that mediates the activity of TOFA and hydroxycholesterol on neuronal differentiation in pheochromocytoma cells.

Apicomplexans pulling the strings: manipulation of the host cell cytoskeleton dynamics.

PubMed

Cardoso, Rita; Soares, Helena; Hemphill, Andrew; Leitão, Alexandre

2016-07-01

Invasive stages of apicomplexan parasites require a host cell to survive, proliferate and advance to the next life cycle stage. Once invasion is achieved, apicomplexans interact closely with the host cell cytoskeleton, but in many cases the different species have evolved distinct mechanisms and pathways to modulate the structural organization of cytoskeletal filaments. The host cell cytoskeleton is a complex network, largely, but not exclusively, composed of microtubules, actin microfilaments and intermediate filaments, all of which are modulated by associated proteins, and it is involved in diverse functions including maintenance of cell morphology and mechanical support, migration, signal transduction, nutrient uptake, membrane and organelle trafficking and cell division. The ability of apicomplexans to modulate the cytoskeleton to their own advantage is clearly beneficial. We here review different aspects of the interactions of apicomplexans with the three main cytoskeletal filament types, provide information on the currently known parasite effector proteins and respective host cell targets involved, and how these interactions modulate the host cell physiology. Some of these findings could provide novel targets that could be exploited for the development of preventive and/or therapeutic strategies.

Small organelle, big responsibility: the role of centrosomes in development and disease.

PubMed

Chavali, Pavithra L; Pütz, Monika; Gergely, Fanni

2014-09-05

The centrosome, a key microtubule organizing centre, is composed of centrioles, embedded in a protein-rich matrix. Centrosomes control the internal spatial organization of somatic cells, and as such contribute to cell division, cell polarity and migration. Upon exiting the cell cycle, most cell types in the human body convert their centrioles into basal bodies, which drive the assembly of primary cilia, involved in sensing and signal transduction at the cell surface. Centrosomal genes are targeted by mutations in numerous human developmental disorders, ranging from diseases exclusively affecting brain development, through global growth failure syndromes to diverse pathologies associated with ciliary malfunction. Despite our much-improved understanding of centrosome function in cellular processes, we know remarkably little of its role in the organismal context, especially in mammals. In this review, we examine how centrosome dysfunction impacts on complex physiological processes and speculate on the challenges we face when applying knowledge generated from in vitro and in vivo model systems to human development. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Nanoscale architecture of the Schizosaccharomyces pombe contractile ring.

PubMed

McDonald, Nathan A; Lind, Abigail L; Smith, Sarah E; Li, Rong; Gould, Kathleen L

2017-09-15

The contractile ring is a complex molecular apparatus which physically divides many eukaryotic cells. Despite knowledge of its protein composition, the molecular architecture of the ring is not known. Here we have applied super-resolution microscopy and FRET to determine the nanoscale spatial organization of Schizosaccharomyces pombe contractile ring components relative to the plasma membrane. Similar to other membrane-tethered actin structures, we find proteins localize in specific layers relative to the membrane. The most membrane-proximal layer (0-80 nm) is composed of membrane-binding scaffolds, formin, and the tail of the essential myosin-II. An intermediate layer (80-160 nm) consists of a network of cytokinesis accessory proteins as well as multiple signaling components which influence cell division. Farthest from the membrane (160-350 nm) we find F-actin, the motor domains of myosins, and a major F-actin crosslinker. Circumferentially within the ring, multiple proteins proximal to the membrane form clusters of different sizes, while components farther from the membrane are uniformly distributed. This comprehensive organizational map provides a framework for understanding contractile ring function.

Nanoscale architecture of the Schizosaccharomyces pombe contractile ring

PubMed Central

McDonald, Nathan A; Lind, Abigail L; Smith, Sarah E; Li, Rong

2017-01-01

The contractile ring is a complex molecular apparatus which physically divides many eukaryotic cells. Despite knowledge of its protein composition, the molecular architecture of the ring is not known. Here we have applied super-resolution microscopy and FRET to determine the nanoscale spatial organization of Schizosaccharomyces pombe contractile ring components relative to the plasma membrane. Similar to other membrane-tethered actin structures, we find proteins localize in specific layers relative to the membrane. The most membrane-proximal layer (0–80 nm) is composed of membrane-binding scaffolds, formin, and the tail of the essential myosin-II. An intermediate layer (80–160 nm) consists of a network of cytokinesis accessory proteins as well as multiple signaling components which influence cell division. Farthest from the membrane (160–350 nm) we find F-actin, the motor domains of myosins, and a major F-actin crosslinker. Circumferentially within the ring, multiple proteins proximal to the membrane form clusters of different sizes, while components farther from the membrane are uniformly distributed. This comprehensive organizational map provides a framework for understanding contractile ring function. PMID:28914606

Robust Real-Time Music Transcription with a Compositional Hierarchical Model.

PubMed

Pesek, Matevž; Leonardis, Aleš; Marolt, Matija

2017-01-01

The paper presents a new compositional hierarchical model for robust music transcription. Its main features are unsupervised learning of a hierarchical representation of input data, transparency, which enables insights into the learned representation, as well as robustness and speed which make it suitable for real-world and real-time use. The model consists of multiple layers, each composed of a number of parts. The hierarchical nature of the model corresponds well to hierarchical structures in music. The parts in lower layers correspond to low-level concepts (e.g. tone partials), while the parts in higher layers combine lower-level representations into more complex concepts (tones, chords). The layers are learned in an unsupervised manner from music signals. Parts in each layer are compositions of parts from previous layers based on statistical co-occurrences as the driving force of the learning process. In the paper, we present the model's structure and compare it to other hierarchical approaches in the field of music information retrieval. We evaluate the model's performance for the multiple fundamental frequency estimation. Finally, we elaborate on extensions of the model towards other music information retrieval tasks.

Sensor set-up for wireless measurement of automotive rim and wheel parameters in laboratory conditions

NASA Astrophysics Data System (ADS)

Borecki, M.; Prus, P.; Korwin-Pawlowski, M. L.; Rychlik, A.; Kozubel, W.

2017-08-01

Modern rims and wheels are tested at the design and production stages. Tests can be performed in laboratory conditions and on the ride. In the laboratory, complex and costly equipment is used, as for example wheel balancers and impact testers. Modern wheel balancers are equipped with electronic and electro-mechanical units that enable touch-less measurement of dimensions, including precision measurement of radial and lateral wheel run-out, automatic positioning and application of the counterweights, and vehicle wheel set monitoring - tread wear, drift angles and run-out unbalance. Those tests are performed by on-wheel axis measurements with laser distance meters. The impact tester enables dropping of weights from a defined height onto a wheel. Test criteria are the loss of pressure of the tire and generation of cracks in the wheel without direct impact of the falling weights. In the present paper, a set up composed of three accelerometers, a temperature sensor and a pressure sensor is examined as the base of a wheel tester. The sensor set-up configuration, on-line diagnostic and signal transmission are discussed.

Using "StorAge Selection" functions and high resolution isotope data to unravel travel time distributions in headwater catchments

NASA Astrophysics Data System (ADS)

Benettin, Paolo; Soulsby, Chris; Birkel, Christian; Tetzlaff, Doerthe; Botter, Gianluca; Rinaldo, Andrea

2017-04-01

We use high resolution tracer data from the Bruntland Burn catchment (UK) to test theoretical approaches that integrate catchment-scale flow and transport processes in a unified framework centered on selective age sampling by streamflow and evapotranspiration fluxes. Hydrologic transport is here described through StorAge Selection (SAS) functions, parametrized as simple power laws. By representing the way in which catchment storage generates outflows composed by water of different ages, the main mechanism regulating the tracer composition of runoff is clearly identified. The calibrated numerical model provides simulations that convincingly reproduce complex measured signals of daily deuterium content in stream waters during wet and dry periods. The results for the catchment under consideration are consistent with other recent studies indicating a tendency for natural catchments to preferentially release younger available water. The model allows estimating transient water age and its related uncertainty, as well as the total catchment storage. This study shows that power-law SAS functions prove a powerful tool to explain catchment-scale transport processes that also has potential in less intensively monitored sites.

A rapid method for differentiating Saccharomyces sensu stricto strains from other yeast species in an enological environment.

PubMed

Nardi, Tiziana; Carlot, Milena; De Bortoli, Elena; Corich, Viviana; Giacomini, Alessio

2006-11-01

During programs for the selection of enological yeasts, several hundred natural isolates are usually screened. The scope of these operations is to isolate strains possessing good fermentative properties without necessarily arriving at a precise species designation: in other words, to detect strains belonging to the Saccharomyces sensu stricto complex. In the present study, a pair of primers, designed within the variable D1/D2 region of the 26S subunit of ribosomal yeast RNA, have been constructed. These generate an amplification fragment of 471 bp that is specific for the seven Saccharomyces sensu stricto species, while no signal was obtained for Saccharomyces sensu lato strains (17 species) or for another 18 selected species commonly found in enological environments. A second pair of primers was also constructed, within the 18S rRNA gene, composed of perfectly conserved sequences common for all 42 yeast species examined, which generate a 900 bp (c.) band for all strains. This was used as a positive experimental control in multiplex PCR analysis using all four primers.

Complexity of cardiovascular rhythms during head-up tilt test by entropy of patterns.

PubMed

Wejer, Dorota; Graff, Beata; Makowiec, Danuta; Budrejko, Szymon; Struzik, Zbigniew R

2017-05-01

The head-up tilt (HUT) test, which provokes transient dynamical alterations in the regulation of cardiovascular system, provides insights into complex organization of this system. Based on signals with heart period intervals (RR-intervals) and/or systolic blood pressure (SBP), differences in the cardiovascular regulation between vasovagal patients (VVS) and the healthy people group (CG) are investigated. Short-term relations among signal data represented symbolically by three-beat patterns allow to qualify and quantify the complexity of the cardiovascular regulation by Shannon entropy. Four types of patterns: permutation, ordinal, deterministic and dynamical, are used, and different resolutions of signal values in the the symbolization are applied in order to verify how entropy of patterns depends on a way in which values of signals are preprocessed. At rest, in the physiologically important signal resolution ranges, independently of the type of patterns used in estimates, the complexity of SBP signals in VVS is different from the complexity found in CG. Entropy of VVS is higher than CG what could be interpreted as substantial presence of noisy ingredients in SBP of VVS. After tilting this relation switches. Entropy of CG occurs significantly higher than VVS for SBP signals. In the case of RR-intervals and large resolutions, the complexity after the tilt becomes reduced when compared to the complexity of RR-intervals at rest for both groups. However, in the case of VVS patients this reduction is significantly stronger than in CG. Our observations about opposite switches in entropy between CG and VVS might support a hypothesis that baroreflex in VVS affects stronger the heart rate because of the inefficient regulation (possibly impaired local vascular tone alternations) of the blood pressure.

NeuroPigPen: A Scalable Toolkit for Processing Electrophysiological Signal Data in Neuroscience Applications Using Apache Pig

PubMed Central

Sahoo, Satya S.; Wei, Annan; Valdez, Joshua; Wang, Li; Zonjy, Bilal; Tatsuoka, Curtis; Loparo, Kenneth A.; Lhatoo, Samden D.

2016-01-01

The recent advances in neurological imaging and sensing technologies have led to rapid increase in the volume, rate of data generation, and variety of neuroscience data. This “neuroscience Big data” represents a significant opportunity for the biomedical research community to design experiments using data with greater timescale, large number of attributes, and statistically significant data size. The results from these new data-driven research techniques can advance our understanding of complex neurological disorders, help model long-term effects of brain injuries, and provide new insights into dynamics of brain networks. However, many existing neuroinformatics data processing and analysis tools were not built to manage large volume of data, which makes it difficult for researchers to effectively leverage this available data to advance their research. We introduce a new toolkit called NeuroPigPen that was developed using Apache Hadoop and Pig data flow language to address the challenges posed by large-scale electrophysiological signal data. NeuroPigPen is a modular toolkit that can process large volumes of electrophysiological signal data, such as Electroencephalogram (EEG), Electrocardiogram (ECG), and blood oxygen levels (SpO2), using a new distributed storage model called Cloudwave Signal Format (CSF) that supports easy partitioning and storage of signal data on commodity hardware. NeuroPigPen was developed with three design principles: (a) Scalability—the ability to efficiently process increasing volumes of data; (b) Adaptability—the toolkit can be deployed across different computing configurations; and (c) Ease of programming—the toolkit can be easily used to compose multi-step data processing pipelines using high-level programming constructs. The NeuroPigPen toolkit was evaluated using 750 GB of electrophysiological signal data over a variety of Hadoop cluster configurations ranging from 3 to 30 Data nodes. The evaluation results demonstrate that the toolkit is highly scalable and adaptable, which makes it suitable for use in neuroscience applications as a scalable data processing toolkit. As part of the ongoing extension of NeuroPigPen, we are developing new modules to support statistical functions to analyze signal data for brain connectivity research. In addition, the toolkit is being extended to allow integration with scientific workflow systems. NeuroPigPen is released under BSD license at: https://sites.google.com/a/case.edu/neuropigpen/. PMID:27375472

NeuroPigPen: A Scalable Toolkit for Processing Electrophysiological Signal Data in Neuroscience Applications Using Apache Pig.

PubMed

Sahoo, Satya S; Wei, Annan; Valdez, Joshua; Wang, Li; Zonjy, Bilal; Tatsuoka, Curtis; Loparo, Kenneth A; Lhatoo, Samden D

2016-01-01

The recent advances in neurological imaging and sensing technologies have led to rapid increase in the volume, rate of data generation, and variety of neuroscience data. This "neuroscience Big data" represents a significant opportunity for the biomedical research community to design experiments using data with greater timescale, large number of attributes, and statistically significant data size. The results from these new data-driven research techniques can advance our understanding of complex neurological disorders, help model long-term effects of brain injuries, and provide new insights into dynamics of brain networks. However, many existing neuroinformatics data processing and analysis tools were not built to manage large volume of data, which makes it difficult for researchers to effectively leverage this available data to advance their research. We introduce a new toolkit called NeuroPigPen that was developed using Apache Hadoop and Pig data flow language to address the challenges posed by large-scale electrophysiological signal data. NeuroPigPen is a modular toolkit that can process large volumes of electrophysiological signal data, such as Electroencephalogram (EEG), Electrocardiogram (ECG), and blood oxygen levels (SpO2), using a new distributed storage model called Cloudwave Signal Format (CSF) that supports easy partitioning and storage of signal data on commodity hardware. NeuroPigPen was developed with three design principles: (a) Scalability-the ability to efficiently process increasing volumes of data; (b) Adaptability-the toolkit can be deployed across different computing configurations; and (c) Ease of programming-the toolkit can be easily used to compose multi-step data processing pipelines using high-level programming constructs. The NeuroPigPen toolkit was evaluated using 750 GB of electrophysiological signal data over a variety of Hadoop cluster configurations ranging from 3 to 30 Data nodes. The evaluation results demonstrate that the toolkit is highly scalable and adaptable, which makes it suitable for use in neuroscience applications as a scalable data processing toolkit. As part of the ongoing extension of NeuroPigPen, we are developing new modules to support statistical functions to analyze signal data for brain connectivity research. In addition, the toolkit is being extended to allow integration with scientific workflow systems. NeuroPigPen is released under BSD license at: https://sites.google.com/a/case.edu/neuropigpen/.

LC-MS/MS signal suppression effects in the analysis of pesticides in complex environmental matrices.

PubMed

Choi, B K; Hercules, D M; Gusev, A I

2001-02-01

The application of LC separation and mobile phase additives in addressing LC-MS/MS matrix signal suppression effects for the analysis of pesticides in a complex environmental matrix was investigated. It was shown that signal suppression is most significant for analytes eluting early in the LC-MS analysis. Introduction of different buffers (e.g. ammonium formate, ammonium hydroxide, formic acid) into the LC mobile phase was effective in improving signal correlation between the matrix and standard samples. The signal improvement is dependent on buffer concentration as well as LC separation of the matrix components. The application of LC separation alone was not effective in addressing suppression effects when characterizing complex matrix samples. Overloading of the LC column by matrix components was found to significantly contribute to analyte-matrix co-elution and suppression of signal. This signal suppression effect can be efficiently compensated by 2D LC (LC-LC) separation techniques. The effectiveness of buffers and LC separation in improving signal correlation between standard and matrix samples is discussed.

The guitar chord-generating algorithm based on complex network

NASA Astrophysics Data System (ADS)

Ren, Tao; Wang, Yi-fan; Du, Dan; Liu, Miao-miao; Siddiqi, Awais

2016-02-01

This paper aims to generate chords for popular songs automatically based on complex network. Firstly, according to the characteristics of guitar tablature, six chord networks of popular songs by six pop singers are constructed and the properties of all networks are concluded. By analyzing the diverse chord networks, the accompaniment regulations and features are shown, with which the chords can be generated automatically. Secondly, in terms of the characteristics of popular songs, a two-tiered network containing a verse network and a chorus network is constructed. With this network, the verse and chorus can be composed respectively with the random walk algorithm. Thirdly, the musical motif is considered for generating chords, with which the bad chord progressions can be revised. This method can make the accompaniments sound more melodious. Finally, a popular song is chosen for generating chords and the new generated accompaniment sounds better than those done by the composers.

A Reference Proteomic Database of Lactobacillus plantarum CMCC-P0002

PubMed Central

Tian, Wanhong; Yu, Gang; Liu, Xiankai; Wang, Jie; Feng, Erling; Zhang, Xuemin; Chen, Bei; Zeng, Ming; Wang, Hengliang

2011-01-01

Lactobacillus plantarum is a widespread probiotic bacteria found in many fermented food products. In this study, the whole-cell proteins and secretory proteins of L. plantarum were separated by two-dimensional electrophoresis method. A total of 434 proteins were identified by tandem mass spectrometry, including a plasmid-encoded hypothetical protein pLP9000_05. The information of first 20 highest abundance proteins was listed for the further genetic manipulation of L. plantarum, such as construction of high-level expressions system. Furthermore, the first interaction map of L. plantarum was established by Blue-Native/SDS-PAGE technique. A heterodimeric complex composed of maltose phosphorylase Map3 and Map2, and two homodimeric complexes composed of Map3 and Map2 respectively, were identified at the same time, indicating the important roles of these proteins. These findings provided valuable information for the further proteomic researches of L. plantarum. PMID:21998671

A reference proteomic database of Lactobacillus plantarum CMCC-P0002.

PubMed

Zhu, Li; Hu, Wei; Liu, Datao; Tian, Wanhong; Yu, Gang; Liu, Xiankai; Wang, Jie; Feng, Erling; Zhang, Xuemin; Chen, Bei; Zeng, Ming; Wang, Hengliang

2011-01-01

Lactobacillus plantarum is a widespread probiotic bacteria found in many fermented food products. In this study, the whole-cell proteins and secretory proteins of L. plantarum were separated by two-dimensional electrophoresis method. A total of 434 proteins were identified by tandem mass spectrometry, including a plasmid-encoded hypothetical protein pLP9000_05. The information of first 20 highest abundance proteins was listed for the further genetic manipulation of L. plantarum, such as construction of high-level expressions system. Furthermore, the first interaction map of L. plantarum was established by Blue-Native/SDS-PAGE technique. A heterodimeric complex composed of maltose phosphorylase Map3 and Map2, and two homodimeric complexes composed of Map3 and Map2 respectively, were identified at the same time, indicating the important roles of these proteins. These findings provided valuable information for the further proteomic researches of L. plantarum.

Toroidal surface complexes of bacteriophage {phi}12 are responsible for host-cell attachment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leo-Macias, Alejandra; Katz, Garrett; Wei Hui

2011-06-05

Cryo-electron tomography and subtomogram averaging are utilized to determine that the bacteriophage {phi}12, a member of the Cystoviridae family, contains surface complexes that are toroidal in shape, are composed of six globular domains with six-fold symmetry, and have a discrete density connecting them to the virus membrane-envelope surface. The lack of this kind of spike in a reassortant of {phi}12 demonstrates that the gene for the hexameric spike is located in {phi}12's medium length genome segment, likely to the P3 open reading frames which are the proteins involved in viral-host cell attachment. Based on this and on protein mass estimatesmore » derived from the obtained averaged structure, it is suggested that each of the globular domains is most likely composed of a total of four copies of P3a and/or P3c proteins. Our findings may have implications in the study of the evolution of the cystovirus species in regard to their host specificity. - Research Highlights: > Subtomogram averaging reveals enhanced detail of a {phi}12 cystovirus surface protein complex. > The surface protein complex has a toroidal shape and six-fold symmetry. > It is encoded by the medium-size genome segment. > The proteins of the surface complex most likely are one copy of P3a and three copies of P3c.« less

How we hear what is not there: A neural mechanism for the missing fundamental illusion

NASA Astrophysics Data System (ADS)

Chialvo, Dante R.

2003-12-01

How the brain estimates the pitch of a complex sound remains unsolved. Complex sounds are composed of more than one tone. When two tones occur together, a third lower pitched tone is often heard. This is referred to as the "missing fundamental illusion" because the perceived pitch is a frequency (fundamental) for which there is no actual source vibration. This phenomenon exemplifies a larger variety of problems related to how pitch is extracted from complex tones, music and speech, and thus has been extensively used to test theories of pitch perception. A noisy nonlinear process is presented here as a candidate neural mechanism to explain the majority of reported phenomenology and provide specific quantitative predictions. The two basic premises of this model are as follows: (I) The individual tones composing the complex tones add linearly producing peaks of constructive interference whose amplitude is always insufficient to fire the neuron (II): The spike threshold is reached only with noise, which naturally selects the maximum constructive interferences. The spacing of these maxima, and consequently the spikes, occurs at a rate identical to the perceived pitch for the complex tone. Comparison with psychophysical and physiological data reveals a remarkable quantitative agreement not dependent on adjustable parameters. In addition, results from numerical simulations across different models are consistent, suggesting relevance to other sensory modalities.

Chitin-Like Molecules Associate with Cryptococcus neoformans Glucuronoxylomannan To Form a Glycan Complex with Previously Unknown Properties

PubMed Central

Ramos, Caroline L.; Fonseca, Fernanda L.; Rodrigues, Jessica; Guimarães, Allan J.; Cinelli, Leonardo P.; Miranda, Kildare; Nimrichter, Leonardo; Casadevall, Arturo; Travassos, Luiz R.

2012-01-01

In prior studies, we demonstrated that glucuronoxylomannan (GXM), the major capsular polysaccharide of the fungal pathogen Cryptococcus neoformans, interacts with chitin oligomers at the cell wall-capsule interface. The structural determinants regulating these carbohydrate-carbohydrate interactions, as well as the functions of these structures, have remained unknown. In this study, we demonstrate that glycan complexes composed of chitooligomers and GXM are formed during fungal growth and macrophage infection by C. neoformans. To investigate the required determinants for the assembly of chitin-GXM complexes, we developed a quantitative scanning electron microscopy-based method using different polysaccharide samples as inhibitors of the interaction of chitin with GXM. This assay revealed that chitin-GXM association involves noncovalent bonds and large GXM fibers and depends on the N-acetyl amino group of chitin. Carboxyl and O-acetyl groups of GXM are not required for polysaccharide-polysaccharide interactions. Glycan complex structures composed of cryptococcal GXM and chitin-derived oligomers were tested for their ability to induce pulmonary cytokines in mice. They were significantly more efficient than either GXM or chitin oligomers alone in inducing the production of lung interleukin 10 (IL-10), IL-17, and tumor necrosis factor alpha (TNF-α). These results indicate that association of chitin-derived structures with GXM through their N-acetyl amino groups generates glycan complexes with previously unknown properties. PMID:22562469

The oncoprotein Ski acts as an antagonist of transforming growth factor-beta signaling by suppressing Smad2 phosphorylation.

PubMed

Prunier, Celine; Pessah, Marcia; Ferrand, Nathalie; Seo, Su Ryeon; Howe, Philip; Atfi, Azeddine

2003-07-11

The phosphorylation of Smad2 and Smad3 by the transforming growth factor (TGF)-beta-activated receptor kinases and their subsequent heterodimerization with Smad4 and translocation to the nucleus form the basis for a model how Smad proteins work to transmit TGF-beta signals. The transcriptional activity of Smad2-Smad4 or Smad3-Smad4 complexes can be limited by the corepressor Ski, which is believed to interact with Smad complexes on TGF-beta-responsive promoters and represses their ability to activate TGF-beta target genes by assembling on DNA a repressor complex containing histone deacetylase. Here we show that Ski can block TGF-beta signaling by interfering with the phosphorylation of Smad2 and Smad3 by the activated TGF-beta type I receptor. Furthermore, we demonstrate that overexpression of Ski induces the assembly of Smad2-Smad4 and Smad3-Smad4 complexes independent of TGF-beta signaling. The ability of Ski to engage Smad proteins in nonproductive complexes provides new insights into the molecular mechanism used by Ski for disabling TGF-beta signaling.

DNA/RNA hybrid substrates modulate the catalytic activity of purified AID.

PubMed

Abdouni, Hala S; King, Justin J; Ghorbani, Atefeh; Fifield, Heather; Berghuis, Lesley; Larijani, Mani

2018-01-01

Activation-induced cytidine deaminase (AID) converts cytidine to uridine at Immunoglobulin (Ig) loci, initiating somatic hypermutation and class switching of antibodies. In vitro, AID acts on single stranded DNA (ssDNA), but neither double-stranded DNA (dsDNA) oligonucleotides nor RNA, and it is believed that transcription is the in vivo generator of ssDNA targeted by AID. It is also known that the Ig loci, particularly the switch (S) regions targeted by AID are rich in transcription-generated DNA/RNA hybrids. Here, we examined the binding and catalytic behavior of purified AID on DNA/RNA hybrid substrates bearing either random sequences or GC-rich sequences simulating Ig S regions. If substrates were made up of a random sequence, AID preferred substrates composed entirely of DNA over DNA/RNA hybrids. In contrast, if substrates were composed of S region sequences, AID preferred to mutate DNA/RNA hybrids over substrates composed entirely of DNA. Accordingly, AID exhibited a significantly higher affinity for binding DNA/RNA hybrid substrates composed specifically of S region sequences, than any other substrates composed of DNA. Thus, in the absence of any other cellular processes or factors, AID itself favors binding and mutating DNA/RNA hybrids composed of S region sequences. AID:DNA/RNA complex formation and supporting mutational analyses suggest that recognition of DNA/RNA hybrids is an inherent structural property of AID. Copyright © 2017 Elsevier Ltd. All rights reserved.

Performance of an optical encoder based on a nondiffractive beam implemented with a specific photodetection integrated circuit and a diffractive optical element.

PubMed

Quintián, Fernando Perez; Calarco, Nicolás; Lutenberg, Ariel; Lipovetzky, José

2015-09-01

In this paper, we study the incremental signal produced by an optical encoder based on a nondiffractive beam (NDB). The NDB is generated by means of a diffractive optical element (DOE). The detection system is composed by an application specific integrated circuit (ASIC) sensor. The sensor consists of an array of eight concentric annular photodiodes, each one provided with a programmable gain amplifier. In this way, the system is able to synthesize a nonuniform detectivity. The contrast, amplitude, and harmonic content of the sinusoidal output signal are analyzed. The influence of the cross talk among the annular photodiodes is placed in evidence through the dependence of the signal contrast on the wavelength.

Populational equilibrium through exosome-mediated Wnt signaling in tumor progression of diffuse large B-cell lymphoma.

PubMed

Koch, Raphael; Demant, Martin; Aung, Thiha; Diering, Nina; Cicholas, Anna; Chapuy, Bjoern; Wenzel, Dirk; Lahmann, Marlen; Güntsch, Annemarie; Kiecke, Christina; Becker, Sabrina; Hupfeld, Timo; Venkataramani, Vivek; Ziepert, Marita; Opitz, Lennart; Klapper, Wolfram; Trümper, Lorenz; Wulf, Gerald G

2014-04-03

Tumors are composed of phenotypically heterogeneous cell populations. The nongenomic mechanisms underlying transitions and interactions between cell populations are largely unknown. Here, we show that diffuse large B-cell lymphomas possess a self-organized infrastructure comprising side population (SP) and non-SP cells, where transitions between clonogenic states are modulated by exosome-mediated Wnt signaling. DNA methylation modulated SP-non-SP transitions and was correlated with the reciprocal expressions of Wnt signaling pathway agonist Wnt3a in SP cells and the antagonist secreted frizzled-related protein 4 in non-SP cells. Lymphoma SP cells exhibited autonomous clonogenicity and exported Wnt3a via exosomes to neighboring cells, thus modulating population equilibrium in the tumor.

Aging and the complexity of cardiovascular dynamics

NASA Technical Reports Server (NTRS)

Kaplan, D. T.; Furman, M. I.; Pincus, S. M.; Ryan, S. M.; Lipsitz, L. A.; Goldberger, A. L.

1991-01-01

Biomedical signals often vary in a complex and irregular manner. Analysis of variability in such signals generally does not address directly their complexity, and so may miss potentially useful information. We analyze the complexity of heart rate and beat-to-beat blood pressure using two methods motivated by nonlinear dynamics (chaos theory). A comparison of a group of healthy elderly subjects with healthy young adults indicates that the complexity of cardiovascular dynamics is reduced with aging. This suggests that complexity of variability may be a useful physiological marker.

Kurtosis-Based Blind Source Extraction of Complex Non-Circular Signals with Application in EEG Artifact Removal in Real-Time

PubMed Central

Javidi, Soroush; Mandic, Danilo P.; Took, Clive Cheong; Cichocki, Andrzej

2011-01-01

A new class of complex domain blind source extraction algorithms suitable for the extraction of both circular and non-circular complex signals is proposed. This is achieved through sequential extraction based on the degree of kurtosis and in the presence of non-circular measurement noise. The existence and uniqueness analysis of the solution is followed by a study of fast converging variants of the algorithm. The performance is first assessed through simulations on well understood benchmark signals, followed by a case study on real-time artifact removal from EEG signals, verified using both qualitative and quantitative metrics. The results illustrate the power of the proposed approach in real-time blind extraction of general complex-valued sources. PMID:22319461

Phospholipase D and phosphatidic acid in plant defence response: from protein-protein and lipid-protein interactions to hormone signalling.

PubMed

Zhao, Jian

2015-04-01

Phospholipase Ds (PLDs) and PLD-derived phosphatidic acids (PAs) play vital roles in plant hormonal and environmental responses and various cellular dynamics. Recent studies have further expanded the functions of PLDs and PAs into plant-microbe interaction. The molecular diversities and redundant functions make PLD-PA an important signalling complex regulating lipid metabolism, cytoskeleton dynamics, vesicle trafficking, and hormonal signalling in plant defence through protein-protein and protein-lipid interactions or hormone signalling. Different PLD-PA signalling complexes and their targets have emerged as fast-growing research topics for understanding their numerous but not yet established roles in modifying pathogen perception, signal transduction, and downstream defence responses. Meanwhile, advanced lipidomics tools have allowed researchers to reveal further the mechanisms of PLD-PA signalling complexes in regulating lipid metabolism and signalling, and their impacts on jasmonic acid/oxylipins, salicylic acid, and other hormone signalling pathways that essentially mediate plant defence responses. This review attempts to summarize the progress made in spatial and temporal PLD/PA signalling as well as PLD/PA-mediated modification of plant defence. It presents an in-depth discussion on the functions and potential mechanisms of PLD-PA complexes in regulating actin filament/microtubule cytoskeleton, vesicle trafficking, and hormonal signalling, and in influencing lipid metabolism-derived metabolites as critical signalling components in plant defence responses. The discussion puts PLD-PA in a broader context in order to guide future research. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Multifrequency OFDM SAR in Presence of Deception Jamming

NASA Astrophysics Data System (ADS)

Schuerger, Jonathan; Garmatyuk, Dmitriy

2010-12-01

Orthogonal frequency division multiplexing (OFDM) is considered in this paper from the perspective of usage in imaging radar scenarios with deception jamming. OFDM radar signals are inherently multifrequency waveforms, composed of a number of subbands which are orthogonal to each other. While being employed extensively in communications, OFDM has not found comparatively wide use in radar, and, particularly, in synthetic aperture radar (SAR) applications. In this paper, we aim to show the advantages of OFDM-coded radar signals with random subband composition when used in deception jamming scenarios. Two approaches to create a radar signal by the jammer are considered: instantaneous frequency (IF) estimator and digital-RF-memory- (DRFM-) based reproducer. In both cases, the jammer aims to create a copy of a valid target image via resending the radar signal at prescribed time intervals. Jammer signals are derived and used in SAR simulations with three types of signal models: OFDM, linear frequency modulated (LFM), and frequency-hopped (FH). Presented results include simulated peak side lobe (PSL) and peak cross-correlation values for random OFDM signals, as well as simulated SAR imagery with IF and DRFM jammers'-induced false targets.

Improvement of absolute positioning of precision stage based on cooperation the zero position pulse signal and incremental displacement signal

NASA Astrophysics Data System (ADS)

Wang, H. H.; Shi, Y. P.; Li, X. H.; Ni, K.; Zhou, Q.; Wang, X. H.

2018-03-01

In this paper, a scheme to measure the position of precision stages, with a high precision, is presented. The encoder is composed of a scale grating and a compact two-probe reading head, to read the zero position pulse signal and continuous incremental displacement signal. The scale grating contains different codes, multiple reference codes with different spacing superimposed onto the incremental grooves with an equal spacing structure. The codes of reference mask in the reading head is the same with the reference codes on the scale grating, and generate pulse signal to locate the reference position primarily when the reading head moves along the scale grating. After locating the reference position in a section by means of the pulse signal, the reference position can be located precisely with the amplitude of the incremental displacement signal. A kind of reference codes and scale grating were designed, and experimental results show that the primary precision of the design achieved is 1 μ m. The period of the incremental signal is 1μ m, and 1000/N nm precision can be achieved by subdivide the incremental signal in N times.

Reversible Gating of Plasmonic Coupling for Optical Signal Amplification.

PubMed

Khoury, Christopher G; Fales, Andrew M; Vo-Dinh, Tuan

2016-07-20

Amplification of optical signals is useful for a wide variety of applications, ranging from data signal transmission to chemical sensing and biomedical diagnostics. One such application in chemical sensing is surface-enhanced Raman scattering (SERS), an important technique for increasing the Raman signal using the plasmonic effect of enhanced electromagnetic fields associated with metallic nanostructures. One of the most important limitations of SERS-based amplification is the difficulty to reproducibly control the SERS signal. Here, we describe the design and implementation of a unique hybrid system capable of producing reversible gating of plasmonic coupling for Raman signal amplification. The hybrid system is composed of two subsystems: (1) colloidal magneto-plasmonic nanoparticles for SERS enhancement and (2) a micromagnet substrate with an externally applied magnetic field to modulate the colloidal nanoparticles. For this proof of concept demonstration, the nanoparticles were labeled with a Raman-active dye, and it was shown that the detected SERS signal could be reproducibly modulated by controlling the externally applied magnetic field. The developed system provides a simple, robust, inexpensive, and reusable device for SERS signal modulation. These properties will open up new possibilities for optical signal amplification and gating as well for high-throughput, reproducible SERS detection.

A Complex mTOR Response in Habituation Paradigms for a Social Signal in Adult Songbirds

ERIC Educational Resources Information Center

Ahmadiantehrani, Somayeh; Gores, Elisa O.; London, Sarah E.

2018-01-01

Nonassociative learning is considered simple because it depends on presentation of a single stimulus, but it likely reflects complex molecular signaling. To advance understanding of the molecular mechanisms of one form of nonassociative learning, habituation, for ethologically relevant signals we examined song recognition learning in adult zebra…

The Effects of Aging and Dual Tasking on Human Gait Complexity During Treadmill Walking: A Comparative Study Using Quantized Dynamical Entropy and Sample Entropy.

PubMed

Ahmadi, Samira; Wu, Christine; Sepehri, Nariman; Kantikar, Anuprita; Nankar, Mayur; Szturm, Tony

2018-01-01

Quantized dynamical entropy (QDE) has recently been proposed as a new measure to quantify the complexity of dynamical systems with the purpose of offering a better computational efficiency. This paper further investigates the viability of this method using five different human gait signals. These signals are recorded while normal walking and while performing secondary tasks among two age groups (young and older age groups). The results are compared with the outcomes of previously established sample entropy (SampEn) measure for the same signals. We also study how analyzing segmented and spatially and temporally normalized signal differs from analyzing whole data. Our findings show that human gait signals become more complex as people age and while they are cognitively loaded. Center of pressure (COP) displacement in mediolateral direction is the best signal for showing the gait changes. Moreover, the results suggest that by segmenting data, more information about intrastride dynamical features are obtained. Most importantly, QDE is shown to be a reliable measure for human gait complexity analysis.

Association of STAT2 SNP genotypes and growth phenotypes in heifers from an Angus, Brahman and Romosinuano diallel population

USDA-ARS?s Scientific Manuscript database

Components of the growth endocrine axis regulate growth and reproduction traits in cattle. A SNP in the promoter of the signal transducer and activator of transcription 2 (STAT2) has been previously reported to be associated with postpartum rebreeding in a diallel beef population composed of 650 hei...

Postural Control in Children, Teenagers and Adults with Down Syndrome

ERIC Educational Resources Information Center

Rigoldi, Chiara; Galli, Manuela; Mainardi, Luca; Crivellini, Marcello; Albertini, Giorgio

2011-01-01

The goal of this work was to analyze postural control in Down syndrome (DS) participants considering three different groups composed by children, teenagers and adults with DS. An analysis of the centre of pressure (COP) displacement during standing position was therefore performed for the three groups of subjects. The obtained signal of COP was…

MONTAGE: A Methodology for Designing Composable End-to-End Secure Distributed Systems

DTIC Science & Technology

2012-08-01

83 7.6 Formal Model of Loc Separation . . . . . . . . . . . . . . . . . . . . . . . . . 84 7.6.1 Static Partitions...Next, we derive five requirements (called Loc Separation, Implicit Parameter Separation, Error Signaling Separation, Conf Separation, and Next Call...hypervisors and hardware) and a real cloud (with shared hypervisors and hardware) that satisfies these requirements. Finally we study Loc Separation

Verbal Recall of Auditory and Visual Signals by Normal and Deficient Reading Children.

ERIC Educational Resources Information Center

Levine, Maureen Julianne

Verbal recall of bisensory memory tasks was compared among 48 9- to 12-year old boys in three groups: normal readers, primary deficit readers, and secondary deficit readers. Auditory and visual stimulus pairs composed of digits, which incorporated variations of intersensory and intrasensory conditions were administered to Ss through a Bell and…

Speech as a breakthrough signaling resource in the cognitive evolution of biological complex adaptive systems.

PubMed

Mattei, Tobias A

2014-12-01

In self-adapting dynamical systems, a significant improvement in the signaling flow among agents constitutes one of the most powerful triggering events for the emergence of new complex behaviors. Ackermann and colleagues' comprehensive phylogenetic analysis of the brain structures involved in acoustic communication provides further evidence of the essential role which speech, as a breakthrough signaling resource, has played in the evolutionary development of human cognition viewed from the standpoint of complex adaptive system analysis.