Biochemical Reconstitution of the WAVE Regulatory Complex
Chen, Baoyu; Padrick, Shae B.; Henry, Lisa; Rosen, Michael K.
2014-01-01
The WAVE regulatory complex (WRC) is a 400-KDa heteropentameric protein assembly that plays a central role in controlling actin cytoskeletal dynamics in many cellular processes. The WRC acts by integrating diverse cellular cues and stimulating the actin nucleating activity of the Arp2/3 complex at membranes. Biochemical and biophysical studies of the underlying mechanisms of these processes require large amounts of purified WRC. Recent success in recombinant expression, reconstitution, purification and crystallization of the WRC has greatly advanced our understanding of the inhibition, activation and membrane recruitment mechanisms of this complex. But many important questions remain to be answered. Here we summarize and update the methods developed in our laboratory, which allow reliable and flexible production of tens of milligrams of recombinant WRC of crystallographic quality, sufficient for many biochemical and structural studies. PMID:24630101
Rac1 GTPase activates the WAVE regulatory complex through two distinct binding sites.
Chen, Baoyu; Chou, Hui-Ting; Brautigam, Chad A; Xing, Wenmin; Yang, Sheng; Henry, Lisa; Doolittle, Lynda K; Walz, Thomas; Rosen, Michael K
2017-09-26
The Rho GTPase Rac1 activates the WAVE regulatory complex (WRC) to drive Arp2/3 complex-mediated actin polymerization, which underpins diverse cellular processes. Here we report the structure of a WRC-Rac1 complex determined by cryo-electron microscopy. Surprisingly, Rac1 is not located at the binding site on the Sra1 subunit of the WRC previously identified by mutagenesis and biochemical data. Rather, it binds to a distinct, conserved site on the opposite end of Sra1. Biophysical and biochemical data on WRC mutants confirm that Rac1 binds to both sites, with the newly identified site having higher affinity and both sites required for WRC activation. Our data reveal that the WRC is activated by simultaneous engagement of two Rac1 molecules, suggesting a mechanism by which cells may sense the density of active Rac1 at membranes to precisely control actin assembly.
Pauker, Maor H; Reicher, Barak; Joseph, Noah; Wortzel, Inbal; Jakubowicz, Shlomi; Noy, Elad; Perl, Orly; Barda-Saad, Mira
2014-12-12
T cell antigen receptor (TCR) engagement has been shown to activate pathways leading to actin cytoskeletal polymerization and reorganization, which are essential for lymphocyte activation and function. Several actin regulatory proteins were implicated in regulating the actin machinery, such as members of the Wiskott-Aldrich syndrome protein (WASp) family. These include WASp and the WASp family verprolin-homologous protein-2 (WAVE2). Although WASp and WAVE2 share several structural features, the precise regulatory mechanisms and potential redundancy between them have not been fully characterized. Specifically, unlike WASp, the dynamic molecular interactions that regulate WAVE2 recruitment to the cell membrane and specifically to the TCR signaling complex are largely unknown. Here, we identify the molecular mechanism that controls the recruitment of WAVE2 in comparison with WASp. Using fluorescence resonance energy transfer (FRET) and novel triple-color FRET (3FRET) technology, we demonstrate how WAVE2 signaling complexes are dynamically regulated during lymphocyte activation in vivo. We show that, similar to WASp, WAVE2 recruitment to the TCR site depends on protein-tyrosine kinase, ZAP-70, and the adaptors LAT, SLP-76, and Nck. However, in contrast to WASp, WAVE2 leaves this signaling complex and migrates peripherally together with vinculin to the membrane leading edge. Our experiments demonstrate that WASp and WAVE2 differ in their dynamics and their associated proteins. Thus, this study reveals the differential mechanisms regulating the function of these cytoskeletal proteins. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
Pauker, Maor H.; Reicher, Barak; Joseph, Noah; Wortzel, Inbal; Jakubowicz, Shlomi; Noy, Elad; Perl, Orly; Barda-Saad, Mira
2014-01-01
T cell antigen receptor (TCR) engagement has been shown to activate pathways leading to actin cytoskeletal polymerization and reorganization, which are essential for lymphocyte activation and function. Several actin regulatory proteins were implicated in regulating the actin machinery, such as members of the Wiskott-Aldrich syndrome protein (WASp) family. These include WASp and the WASp family verprolin-homologous protein-2 (WAVE2). Although WASp and WAVE2 share several structural features, the precise regulatory mechanisms and potential redundancy between them have not been fully characterized. Specifically, unlike WASp, the dynamic molecular interactions that regulate WAVE2 recruitment to the cell membrane and specifically to the TCR signaling complex are largely unknown. Here, we identify the molecular mechanism that controls the recruitment of WAVE2 in comparison with WASp. Using fluorescence resonance energy transfer (FRET) and novel triple-color FRET (3FRET) technology, we demonstrate how WAVE2 signaling complexes are dynamically regulated during lymphocyte activation in vivo. We show that, similar to WASp, WAVE2 recruitment to the TCR site depends on protein-tyrosine kinase, ZAP-70, and the adaptors LAT, SLP-76, and Nck. However, in contrast to WASp, WAVE2 leaves this signaling complex and migrates peripherally together with vinculin to the membrane leading edge. Our experiments demonstrate that WASp and WAVE2 differ in their dynamics and their associated proteins. Thus, this study reveals the differential mechanisms regulating the function of these cytoskeletal proteins. PMID:25342748
Joseph, Noah; Biber, Guy; Fried, Sophia; Reicher, Barak; Levy, Omer; Sabag, Batel; Noy, Elad; Barda-Saad, Mira
2017-01-01
WASp family Verprolin-homologous protein-2 (WAVE2), a member of the Wiskott-Aldrich syndrome protein (WASp) family of actin nucleation promoting factors, is a central regulator of actin cytoskeleton polymerization and dynamics. Multiple signaling pathways operate via WAVE2 to promote the actin-nucleating activity of the actin-related protein 2/3 (Arp2/3) complex. WAVE2 exists as a part of a pentameric protein complex known as the WAVE regulatory complex (WRC), which is unstable in the absence of its individual proteins. While the involvement of WAVE2 in actin polymerization has been well documented, its negative regulation mechanism is poorly characterized to date. Here, we demonstrate that WAVE2 undergoes ubiquitylation in a T-cell activation dependent manner, followed by proteasomal degradation. The WAVE2 ubiquitylation site was mapped to lysine 45, located at the N-terminus where WAVE2 binds to the WRC. Using Förster resonance energy transfer (FRET), we reveal that the autoinhibitory conformation of the WRC maintains the stability of WAVE2 in resting cells; the release of autoinhibition following T-cell activation facilitates the exposure of WAVE2 to ubiquitylation, leading to its degradation. The dynamic conformational structures of WAVE2 during cellular activation dictate its degradation. PMID:28332566
Joseph, Noah; Biber, Guy; Fried, Sophia; Reicher, Barak; Levy, Omer; Sabag, Batel; Noy, Elad; Barda-Saad, Mira
2017-03-23
WASp family Verprolin-homologous protein-2 (WAVE2), a member of the Wiskott-Aldrich syndrome protein (WASp) family of actin nucleation promoting factors, is a central regulator of actin cytoskeleton polymerization and dynamics. Multiple signaling pathways operate via WAVE2 to promote the actin-nucleating activity of the actin-related protein 2/3 (Arp2/3) complex. WAVE2 exists as a part of a pentameric protein complex known as the WAVE regulatory complex (WRC), which is unstable in the absence of its individual proteins. While the involvement of WAVE2 in actin polymerization has been well documented, its negative regulation mechanism is poorly characterized to date. Here, we demonstrate that WAVE2 undergoes ubiquitylation in a T-cell activation dependent manner, followed by proteasomal degradation. The WAVE2 ubiquitylation site was mapped to lysine 45, located at the N-terminus where WAVE2 binds to the WRC. Using Förster resonance energy transfer (FRET), we reveal that the autoinhibitory conformation of the WRC maintains the stability of WAVE2 in resting cells; the release of autoinhibition following T-cell activation facilitates the exposure of WAVE2 to ubiquitylation, leading to its degradation. The dynamic conformational structures of WAVE2 during cellular activation dictate its degradation.
ERK-MAPK drives lamellipodia protrusion by activating the WAVE2 regulatory complex.
Mendoza, Michelle C; Er, E Emrah; Zhang, Wenjuan; Ballif, Bryan A; Elliott, Hunter L; Danuser, Gaudenz; Blenis, John
2011-03-18
Cell movement begins with a leading edge protrusion, which is stabilized by nascent adhesions and retracted by mature adhesions. The ERK-MAPK (extracellular signal-regulated kinase-mitogen-activated protein kinase) localizes to protrusions and adhesions, but how it regulates motility is not understood. We demonstrate that ERK controls protrusion initiation and protrusion speed. Lamellipodial protrusions are generated via the WRC (WAVE2 regulatory complex), which activates the Arp2/3 actin nucleator for actin assembly. The WRC must be phosphorylated to be activated, but the sites and kinases that regulate its intermolecular changes and membrane recruitment are unknown. We show that ERK colocalizes with the WRC at lamellipodial leading edges and directly phosphorylates two WRC components: WAVE2 and Abi1. The phosphorylations are required for functional WRC interaction with Arp2/3 and actin during cell protrusion. Thus, ERK coordinates adhesion disassembly with WRC activation and actin polymerization to promote productive leading edge advancement during cell migration. Copyright © 2011 Elsevier Inc. All rights reserved.
ERK-MAPK Drives Lamellipodia Protrusion by Activating the WAVE2 Regulatory Complex
Mendoza, Michelle C.; Emrah, E.; Zhang, Wenjuan; Ballif, Bryan A.; Elliott, Hunter L.; Danuser, Gaudenz; Blenis, John
2011-01-01
Summary Cell movement begins with a leading edge protrusion, which is stabilized by nascent adhesions and retracted by mature adhesions. The ERK-MAPK (extracellular signal regulated kinasemitogen-activated protein kinase) localizes to protrusions and adhesions, but how it regulates motility is not understood. We demonstrate ERK controls protrusion initiation and protrusion speed. Lamellipodial protrusions are generated via the WRC (WAVE2 Regulatory Complex), which activates the Arp2/3 actin nucleator for actin assembly. The WRC must be phosphorylated to be activated, but the sites and kinases that regulate its intermolecular changes and membrane recruitment are unknown. We show ERK co-localizes with the WRC at lamellipodial leading edges and directly phosphorylates two WRC components: WAVE2 and Abi1. The phosphorylations are required for functional WRC interaction with Arp2/3 and actin during cell protrusion. Thus, ERK coordinates adhesion disassembly with WRC activation and actin polymerization to promote productive leading edge advancement during cell migration. PMID:21419341
Nolz, Jeffrey C; Nacusi, Lucas P; Segovis, Colin M; Medeiros, Ricardo B; Mitchell, Jason S; Shimizu, Yoji; Billadeau, Daniel D
2008-09-22
WAVE2 regulates T cell receptor (TCR)-stimulated actin cytoskeletal dynamics leading to both integrin clustering and affinity maturation. Although WAVE2 mediates integrin affinity maturation by recruiting vinculin and talin to the immunological synapse in an Arp2/3-dependent manner, the mechanism by which it regulates integrin clustering is unclear. We show that the Abl tyrosine kinase associates with the WAVE2 complex and TCR ligation induces WAVE2-dependent membrane recruitment of Abl. Furthermore, we show that WAVE2 regulates TCR-mediated activation of the integrin regulatory guanosine triphosphatase Rap1 via the recruitment and activation of the CrkL-C3G exchange complex. Moreover, we demonstrate that although Abl does not regulate the recruitment of CrkL-C3G into the membrane, it does affect the tyrosine phosphorylation of C3G, which is required for its guanine nucleotide exchange factor activity toward Rap1. This signaling node regulates not only TCR-stimulated integrin clustering but also affinity maturation. These findings identify a previously unknown mechanism by which the WAVE2 complex regulates TCR signaling to Rap1 and integrin activation.
Nolz, Jeffrey C.; Nacusi, Lucas P.; Segovis, Colin M.; Medeiros, Ricardo B.; Mitchell, Jason S.; Shimizu, Yoji; Billadeau, Daniel D.
2008-01-01
WAVE2 regulates T cell receptor (TCR)–stimulated actin cytoskeletal dynamics leading to both integrin clustering and affinity maturation. Although WAVE2 mediates integrin affinity maturation by recruiting vinculin and talin to the immunological synapse in an Arp2/3-dependent manner, the mechanism by which it regulates integrin clustering is unclear. We show that the Abl tyrosine kinase associates with the WAVE2 complex and TCR ligation induces WAVE2-dependent membrane recruitment of Abl. Furthermore, we show that WAVE2 regulates TCR-mediated activation of the integrin regulatory guanosine triphosphatase Rap1 via the recruitment and activation of the CrkL–C3G exchange complex. Moreover, we demonstrate that although Abl does not regulate the recruitment of CrkL–C3G into the membrane, it does affect the tyrosine phosphorylation of C3G, which is required for its guanine nucleotide exchange factor activity toward Rap1. This signaling node regulates not only TCR-stimulated integrin clustering but also affinity maturation. These findings identify a previously unknown mechanism by which the WAVE2 complex regulates TCR signaling to Rap1 and integrin activation. PMID:18809728
Liu, Jun; Wang, Qiao-Chu; Wang, Fei; Duan, Xing; Dai, Xiao-Xin; Wang, Teng; Liu, Hong-Lin; Cui, Xiang-Shun; Kim, Nam-Hyung; Sun, Shao-Chen
2012-01-01
The actin nucleation factor Arp2/3 complex is a main regulator of actin assembly and is involved in multiple processes like cell migration and adhesion, endocytosis, and the establishment of cell polarity in mitosis. Our previous work showed that the Arp2/3 complex was involved in the actin-mediated mammalian oocyte asymmetric division. However, the regulatory mechanisms and signaling pathway of Arp2/3 complex in meiosis is still unclear. In the present work, we identified that the nucleation promoting factors (NPFs) JMY and WAVE2 were necessary for the expression and localization of Arp2/3 complex in mouse oocytes. RNAi of both caused the degradation of actin cap intensity, indicating the roles of NPFs in the formation of actin cap. Moreover, JMY and WAVE2 RNAi decreased the expression of ARP2, a key component of Arp2/3 complex. However, knock down of Arp2/3 complex by Arpc2 and Arpc3 siRNA microinjection did not affect the expression and localization of JMY and WAVE2. Our results indicate that the NPFs, JMY and WAVE2, are upstream regulators of Arp2/3 complex in mammalian oocyte asymmetric division.
Lee, Natalie K.; Fok, Ka Wai; White, Amanda; Wilson, Nicole H.; O'Leary, Conor J.; Cox, Hayley L.; Michael, Magdalene; Yap, Alpha S.; Cooper, Helen M.
2016-01-01
To maintain tissue integrity during epithelial morphogenesis, adherens junctions (AJs) must resist the mechanical stresses exerted by dynamic tissue movements. Junctional stability is dependent on actomyosin contractility within the actin ring. Here we describe a novel function for the axon guidance receptor, Neogenin, as a key component of the actin nucleation machinery governing junctional stability. Loss of Neogenin perturbs AJs and attenuates junctional tension. Neogenin promotes actin nucleation at AJs by recruiting the Wave regulatory complex (WRC) and Arp2/3. A direct interaction between the Neogenin WIRS domain and the WRC is crucial for the spatially restricted recruitment of the WRC to the junction. Thus, we provide the first example of a functional WIRS–WRC interaction in epithelia. We further show that Neogenin regulates cadherin recycling at the AJ. In summary, we identify Neogenin as a pivotal component of the AJ, where it influences both cadherin dynamics and junctional tension. PMID:27029596
Liu, Jun; Wang, Qiao-Chu; Wang, Fei; Duan, Xing; Dai, Xiao-Xin; Wang, Teng; Liu, Hong-Lin; Cui, Xiang-Shun; Kim, Nam-Hyung; Sun, Shao-Chen
2012-01-01
The actin nucleation factor Arp2/3 complex is a main regulator of actin assembly and is involved in multiple processes like cell migration and adhesion, endocytosis, and the establishment of cell polarity in mitosis. Our previous work showed that the Arp2/3 complex was involved in the actin-mediated mammalian oocyte asymmetric division. However, the regulatory mechanisms and signaling pathway of Arp2/3 complex in meiosis is still unclear. In the present work, we identified that the nucleation promoting factors (NPFs) JMY and WAVE2 were necessary for the expression and localization of Arp2/3 complex in mouse oocytes. RNAi of both caused the degradation of actin cap intensity, indicating the roles of NPFs in the formation of actin cap. Moreover, JMY and WAVE2 RNAi decreased the expression of ARP2, a key component of Arp2/3 complex. However, knock down of Arp2/3 complex by Arpc2 and Arpc3 siRNA microinjection did not affect the expression and localization of JMY and WAVE2. Our results indicate that the NPFs, JMY and WAVE2, are upstream regulators of Arp2/3 complex in mammalian oocyte asymmetric division. PMID:23272233
Cioni, Jean-Michel; Wong, Hovy Ho-Wai; Bressan, Dario; Kodama, Lay; Harris, William A; Holt, Christine E
2018-03-07
The axons of retinal ganglion cells (RGCs) are topographically sorted before they arrive at the optic tectum. This pre-target sorting, typical of axon tracts throughout the brain, is poorly understood. Here, we show that cytoplasmic FMR1-interacting proteins (CYFIPs) fulfill non-redundant functions in RGCs, with CYFIP1 mediating axon growth and CYFIP2 specifically involved in axon sorting. We find that CYFIP2 mediates homotypic and heterotypic contact-triggered fasciculation and repulsion responses between dorsal and ventral axons. CYFIP2 associates with transporting ribonucleoprotein particles in axons and regulates translation. Axon-axon contact stimulates CYFIP2 to move into growth cones where it joins the actin nucleating WAVE regulatory complex (WRC) in the periphery and regulates actin remodeling and filopodial dynamics. CYFIP2's function in axon sorting is mediated by its binding to the WRC but not its translational regulation. Together, these findings uncover CYFIP2 as a key regulatory link between axon-axon interactions, filopodial dynamics, and optic tract sorting. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
WAVE2 Protein Complex Coupled to Membrane and Microtubules.
Takahashi, Kazuhide
2012-01-01
E-cadherin is one of the key molecules in the formation of cell-cell adhesion and interacts intracellularly with a group of proteins collectively named catenins, through which the E-cadherin-catenin complex is anchored to actin-based cytoskeletal components. Although cell-cell adhesion is often disrupted in cancer cells by either genetic or epigenetic alterations in cell adhesion molecules, disruption of cell-cell adhesion alone seems to be insufficient for the induction of cancer cell migration and invasion. A small GTP-binding protein, Rac1, induces the specific cellular protrusions lamellipodia via WAVE2, a member of WASP/WAVE family of the actin cytoskeletal regulatory proteins. Biochemical and pharmacological investigations have revealed that WAVE2 interacts with many proteins that regulate microtubule growth, actin assembly, and membrane targeting of proteins, all of which are necessary for directional cell migration through lamellipodia formation. These findings might have important implications for the development of effective therapeutic agents against cancer cell migration and invasion.
WAVE2 Protein Complex Coupled to Membrane and Microtubules
Takahashi, Kazuhide
2012-01-01
E-cadherin is one of the key molecules in the formation of cell-cell adhesion and interacts intracellularly with a group of proteins collectively named catenins, through which the E-cadherin-catenin complex is anchored to actin-based cytoskeletal components. Although cell-cell adhesion is often disrupted in cancer cells by either genetic or epigenetic alterations in cell adhesion molecules, disruption of cell-cell adhesion alone seems to be insufficient for the induction of cancer cell migration and invasion. A small GTP-binding protein, Rac1, induces the specific cellular protrusions lamellipodia via WAVE2, a member of WASP/WAVE family of the actin cytoskeletal regulatory proteins. Biochemical and pharmacological investigations have revealed that WAVE2 interacts with many proteins that regulate microtubule growth, actin assembly, and membrane targeting of proteins, all of which are necessary for directional cell migration through lamellipodia formation. These findings might have important implications for the development of effective therapeutic agents against cancer cell migration and invasion. PMID:22315597
Leng, Yan; Zhang, Jinyi; Badour, Karen; Arpaia, Enrico; Freeman, Spencer; Cheung, Pam; Siu, Michael; Siminovitch, Katherine
2005-01-25
WAVE2 is a member of the Wiskott-Aldrich syndrome protein family of cytoskeletal regulatory proteins shown to link Rac activation to actin remodeling via induction of Arp 2/3 activity. WAVE2 is thought to be regulated by its positioning in a macromolecular complex also containing the Abelson-(Abl) interactor-1 (Abi-1) adaptor, but the molecular basis and biologic relevance of WAVE2 inclusion in this complex are ill defined. Here we show that Abi-1 binding to WAVE2 is mediated by discrete motifs in the Abi-1 coiled-coil and WAVE2 WAVE-homology domains and increases markedly in conjunction with Abi-1-WAVE2 translocation and colocalization at the leading edge in B16F1 cells after fibronectin stimulation. Abi-1 also couples WAVE2 to Abl after cell stimulation, an interaction that triggers Abl membrane translocation with WAVE2, Abi-1, and activated Rac, as well as Abl-mediated tyrosine phosphorylation and WAVE2 activation. By contrast, mutation of tyrosine residue Y150, identified here as the major site of Abl-mediated WAVE2 tyrosine phosphorylation, as well as disruption of WAVE2-Abi-1 binding, impairs induction of WAVE2-driven actin polymerization and its membrane translocation in association with activated Rac. Similarly, WAVE2 tyrosine phosphorylation and induction of membrane actin rearrangement are abrogated in fibroblasts lacking the Abl family kinase. Together, these data reveal that Abi-1-mediated coupling of Abl to WAVE2 promotes Abl-evoked WAVE2 tyrosine phosphorylation required to link WAVE2 with activated Rac and with actin polymerization and remodeling at the cell periphery.
De Rubeis, Silvia; Pasciuto, Emanuela; Li, Ka Wan; Fernández, Esperanza; Di Marino, Daniele; Buzzi, Andrea; Ostroff, Linnaea E.; Klann, Eric; Zwartkruis, Fried J.T.; Komiyama, Noboru H.; Grant, Seth G.N.; Poujol, Christel; Choquet, Daniel; Achsel, Tilmann; Posthuma, Danielle; Smit, August B.; Bagni, Claudia
2013-01-01
Summary The CYFIP1/SRA1 gene is located in a chromosomal region linked to various neurological disorders, including intellectual disability, autism, and schizophrenia. CYFIP1 plays a dual role in two apparently unrelated processes, inhibiting local protein synthesis and favoring actin remodeling. Here, we show that brain-derived neurotrophic factor (BDNF)-driven synaptic signaling releases CYFIP1 from the translational inhibitory complex, triggering translation of target mRNAs and shifting CYFIP1 into the WAVE regulatory complex. Active Rac1 alters the CYFIP1 conformation, as demonstrated by intramolecular FRET, and is key in changing the equilibrium of the two complexes. CYFIP1 thus orchestrates the two molecular cascades, protein translation and actin polymerization, each of which is necessary for correct spine morphology in neurons. The CYFIP1 interactome reveals many interactors associated with brain disorders, opening new perspectives to define regulatory pathways shared by neurological disabilities characterized by spine dysmorphogenesis. PMID:24050404
Philipson, Casandra W.; Bassaganya-Riera, Josep; Viladomiu, Monica; Kronsteiner, Barbara; Abedi, Vida; Hoops, Stefan; Michalak, Pawel; Kang, Lin; Girardin, Stephen E.; Hontecillas, Raquel
2015-01-01
Helicobacter pylori colonizes half of the world’s population as the dominant member of the gastric microbiota resulting in a lifelong chronic infection. Host responses toward the bacterium can result in asymptomatic, pathogenic or even favorable health outcomes; however, mechanisms underlying the dual role of H. pylori as a commensal versus pathogenic organism are not well characterized. Recent evidence suggests mononuclear phagocytes are largely involved in shaping dominant immunity during infection mediating the balance between host tolerance and succumbing to overt disease. We combined computational modeling, bioinformatics and experimental validation in order to investigate interactions between macrophages and intracellular H. pylori. Global transcriptomic analysis on bone marrow-derived macrophages (BMDM) in a gentamycin protection assay at six time points unveiled the presence of three sequential host response waves: an early transient regulatory gene module followed by sustained and late effector responses. Kinetic behaviors of pattern recognition receptors (PRRs) are linked to differential expression of spatiotemporal response waves and function to induce effector immunity through extracellular and intracellular detection of H. pylori. We report that bacterial interaction with the host intracellular environment caused significant suppression of regulatory NLRC3 and NLRX1 in a pattern inverse to early regulatory responses. To further delineate complex immune responses and pathway crosstalk between effector and regulatory PRRs, we built a computational model calibrated using time-series RNAseq data. Our validated computational hypotheses are that: 1) NLRX1 expression regulates bacterial burden in macrophages; and 2) early host response cytokines down-regulate NLRX1 expression through a negative feedback circuit. This paper applies modeling approaches to characterize the regulatory role of NLRX1 in mechanisms of host tolerance employed by macrophages to respond to and/or to co-exist with intracellular H. pylori. PMID:26367386
Clinical Trial of a Comprehensive Treatment for High Functioning Children with ASD
2017-07-01
and completion of the regulatory review; (2) implementation of the treatment for sampling wave 2; (3) completion of pretest , posttest , and follow-up...implementation of the treatment for sampling wave 3; (7) completion of pretest , posttest , and follow-up measures for sampling wave 3; (8) enrollment of...of the regulatory review; (2) implementation of the treatment for sampling wave 2; (3) completion of pretest , posttest , and follow-up measures for
Zhang, Chunhua; Mallery, Eileen; Reagan, Sara; Boyko, Vitaly P.; Kotchoni, Simeon O.; Szymanski, Daniel B.
2013-01-01
During plant cell morphogenesis, signal transduction and cytoskeletal dynamics interact to locally organize the cytoplasm and define the geometry of cell expansion. The WAVE/SCAR (for WASP family verprolin homologous/suppressor of cyclic AMP receptor) regulatory complex (W/SRC) is an evolutionarily conserved heteromeric protein complex. Within the plant kingdom W/SRC is a broadly used effector that converts Rho-of-Plants (ROP)/Rac small GTPase signals into Actin-Related Protein2/3 and actin-dependent growth responses. Although the components and biochemistry of the W/SRC pathway are well understood, a basic understanding of how cells partition W/SRC into active and inactive pools is lacking. In this paper, we report that the endoplasmic reticulum (ER) is an important organelle for W/SRC regulation. We determined that a large intracellular pool of the core W/SRC subunit NAP1, like the known positive regulator of W/SRC, the DOCK family guanine nucleotide-exchange factor SPIKE1 (SPK1), localizes to the surface of the ER. The ER-associated NAP1 is inactive because it displays little colocalization with the actin network, and ER localization requires neither activating signals from SPK1 nor a physical association with its W/SRC-binding partner, SRA1. Our results indicate that in Arabidopsis (Arabidopsis thaliana) leaf pavement cells and trichomes, the ER is a reservoir for W/SRC signaling and may have a key role in the early steps of W/SRC assembly and/or activation. PMID:23613272
Cell based advanced therapeutic medicinal products for bone repair: Keep it simple?
Leijten, J; Chai, Y C; Papantoniou, I; Geris, L; Schrooten, J; Luyten, F P
2015-04-01
The development of cell based advanced therapeutic medicinal products (ATMPs) for bone repair has been expected to revolutionize the health care system for the clinical treatment of bone defects. Despite this great promise, the clinical outcomes of the few cell based ATMPs that have been translated into clinical treatments have been far from impressive. In part, the clinical outcomes have been hampered because of the simplicity of the first wave of products. In response the field has set-out and amassed a plethora of complexities to alleviate the simplicity induced limitations. Many of these potential second wave products have remained "stuck" in the development pipeline. This is due to a number of reasons including the lack of a regulatory framework that has been evolving in the last years and the shortage of enabling technologies for industrial manufacturing to deal with these novel complexities. In this review, we reflect on the current ATMPs and give special attention to novel approaches that are able to provide complexity to ATMPs in a straightforward manner. Moreover, we discuss the potential tools able to produce or predict 'goldilocks' ATMPs, which are neither too simple nor too complex. Copyright © 2014 Elsevier B.V. All rights reserved.
Evolutionary psychology: new perspectives on cognition and motivation.
Cosmides, Leda; Tooby, John
2013-01-01
Evolutionary psychology is the second wave of the cognitive revolution. The first wave focused on computational processes that generate knowledge about the world: perception, attention, categorization, reasoning, learning, and memory. The second wave views the brain as composed of evolved computational systems, engineered by natural selection to use information to adaptively regulate physiology and behavior. This shift in focus--from knowledge acquisition to the adaptive regulation of behavior--provides new ways of thinking about every topic in psychology. It suggests a mind populated by a large number of adaptive specializations, each equipped with content-rich representations, concepts, inference systems, and regulatory variables, which are functionally organized to solve the complex problems of survival and reproduction encountered by the ancestral hunter-gatherers from whom we are descended. We present recent empirical examples that illustrate how this approach has been used to discover new features of attention, categorization, reasoning, learning, emotion, and motivation.
Nolz, Jeffrey C; Gomez, Timothy S; Zhu, Peimin; Li, Shuixing; Medeiros, Ricardo B; Shimizu, Yoji; Burkhardt, Janis K; Freedman, Bruce D; Billadeau, Daniel D
2006-01-10
The engagement of the T cell receptor results in actin cytoskeletal reorganization at the immune synapse (IS) and the triggering of biochemical signaling cascades leading to gene regulation and, ultimately, cellular activation. Recent studies have identified the WAVE family of proteins as critical mediators of Rac1-induced actin reorganization in other cell types. However, whether these proteins participate in actin reorganization at the IS or signaling pathways in T cells has not been investigated. By using a combination of biochemical, genetic, and cell biology approaches, we provide evidence that WAVE2 is recruited to the IS, is biochemically modified, and is required for actin reorganization and beta-integrin-mediated adhesion after TCR crosslinking. Moreover, we show that WAVE2 regulates calcium entry at a point distal to PLCgamma1 activation and IP(3)-mediated store release. These data reveal a role for WAVE2 in regulating multiple pathways leading to T cell activation. In particular, this work shows that WAVE2 is a key component of the actin regulatory machinery in T cells and that it also participates in linking intracellular calcium store depletion to calcium release-activated calcium (CRAC) channel activation.
NASA Astrophysics Data System (ADS)
Guha, A.; Warren, J.; Cummings, C.; Han, J.
2017-12-01
Thermal stress can induce irreversible photodamage with longer consequences for plant metabolism. We focused on photosystem II (PSII) behaviour to understand how this complex responds in different co-occuring temperate trees exposed to short-term extreme heat waves. The study was designed for understanding complex heat tolerance mechanisms in trees. During manipulative heat-wave experiments, we monitored instantaneous PSII performance and tracked both transient and chronic PSII damages using chlorophyll a fluorescence characteristics. Fluorescence signals were used to simulate PSII bioenergetic processes. The light (Fv'/Fm') and dark-adapted (Fv/Fm) fluorescence traits including fast induction kinetics (OJIP), electron transport rate, PSII operating efficiency and quenching capacities were significantly affected by the heat treatments. Loss in PSII efficiency was more apparent in species like black cottonwood, yellow poplar, walnuts and conifers, whereas oaks maintained relatively better PSII functions. The post-heat recovery of Fv/Fm varied across the studied species showing differential carry over effects. PSII down-regulation was one of dominant factors for the loss in operational photosynthesis during extreme heat wave events. Both light and dark-adapted fluorescence characteristics showed loss in photo-regulatory functions and photodamage. Some resilient species showed rapid recovery from transient PSII damage, whereas fingerprints of chronic PSII damage were observed in susceptibles. Thresholds for Fv/Fm and non-photochemical quenching were identified for the studied species. PSII malfunctioning was largely associated with the observed photosynthetic down-regulation during heat wave treatments, however, its physiological recovery should be a key factor to determine species resilience to short-term extreme heat wave events.
Mishra, Varsha; Puthucheri, Smitha; Singh, Dharmendra
2018-05-07
As a preventive measure against the electromagnetic (EM) wave exposure to human body, EM radiation regulatory authorities such as ICNIRP and FCC defined the value of specific absorption rate (SAR) for the human head during EM wave exposure from mobile phone. SAR quantifies the absorption of EM waves in the human body and it mainly depends on the dielectric properties (ε', σ) of the corresponding tissues. The head part of the human body is more susceptible to EM wave exposure due to the usage of mobile phones. The human head is a complex structure made up of multiple tissues with intermixing of many layers; thus, the accurate measurement of permittivity (ε') and conductivity (σ) of the tissues of the human head is still a challenge. For computing the SAR, researchers are using multilayer model, which has some challenges for defining the boundary for layers. Therefore, in this paper, an attempt has been made to propose a method to compute effective complex permittivity of the human head in the range of 0.3 to 3.0 GHz by applying De-Loor mixing model. Similarly, for defining the thermal effect in the tissue, thermal properties of the human head have also been computed using the De-Loor mixing method. The effective dielectric and thermal properties of equivalent human head model are compared with the IEEE Std. 1528. Graphical abstract ᅟ.
Negative emotions and behaviour: The role of regulatory emotional self-efficacy.
Mesurado, Belén; Vidal, Elisabeth Malonda; Mestre, Anna Llorca
2018-04-01
The objective of this study is to test a longitudinal model that analyses the direct effect of negative emotions (anger, depression and anxiety, wave 1) on prosocial and aggressive behaviour (wave 2) in adolescents. And the indirect effect of negative emotions (wave 1) on prosocial and aggressive behaviour (wave 2) through regulatory emotional self-efficacy. Data was obtained from 417 adolescents in a two-wave longitudinal study (225 girls, M age = 14.70 years) from schools located in Valencia, Spain. SEM was employed to explore longitudinal models. The results showed that anger had a direct relationship with prosocial behaviour and aggression, measured two years later. However, the depression and anxiety states did not predict prosociality and aggressiveness. The mediation role of regulatory emotional self-efficacy between negative emotion and behaviours was only partially confirmed. Finally, only the perception of self-efficacy in expressing positive affect is related to prosociality and aggressiveness. Copyright © 2018 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.
Federal Register 2010, 2011, 2012, 2013, 2014
2012-02-10
... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14291-000] Green Wave Mendocino Wave Park; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments... (FPA), proposing to study the feasibility of the Green Wave Mendocino Wave Park (Mendocino Wave Project...
Final Report Feasibility Study for the California Wave Energy Test Center (CalWavesm)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Blakeslee, Samuel Norman; Toman, William I.; Williams, Richard B.
The California Wave Energy Test Center (CalWave) Feasibility Study project was funded over multiple phases by the Department of Energy to perform an interdisciplinary feasibility assessment to analyze the engineering, permitting, and stakeholder requirements to establish an open water, fully energetic, grid connected, wave energy test center off the coast of California for the purposes of advancing U.S. wave energy research, development, and testing capabilities. Work under this grant included wave energy resource characterization, grid impact and interconnection requirements, port infrastructure and maritime industry capability/suitability to accommodate the industry at research, demonstration and commercial scale, and macro and micro sitingmore » considerations. CalWave Phase I performed a macro-siting and down-selection process focusing on two potential test sites in California: Humboldt Bay and Vandenberg Air Force Base. This work resulted in the Vandenberg Air Force Base site being chosen as the most favorable site based on a peer reviewed criteria matrix. CalWave Phase II focused on four siting location alternatives along the Vandenberg Air Force Base coastline and culminated with a final siting down-selection. Key outcomes from this work include completion of preliminary engineering and systems integration work, a robust turnkey cost estimate, shoreside and subsea hazards assessment, storm wave analysis, lessons learned reports from several maritime disciplines, test center benchmarking as compared to existing international test sites, analysis of existing applicable environmental literature, the completion of a preliminary regulatory, permitting and licensing roadmap, robust interaction and engagement with state and federal regulatory agency personnel and local stakeholders, and the population of a Draft Federal Energy Regulatory Commission (FERC) Preliminary Application Document (PAD). Analysis of existing offshore oil and gas infrastructure was also performed to assess the potential value and re-use scenarios of offshore platform infrastructure and associated subsea power cables and shoreside substations. The CalWave project team was well balanced and was comprised of experts from industry, academia, state and federal regulatory agencies. The result of the CalWave feasibility study finds that the CalWave Test Center has the potential to provide the most viable path to commercialization for wave energy in the United States.« less
Nolz, Jeffrey C.; Gomez, Timothy S.; Zhu, Peimin; Li, Shuixing; Medeiros, Ricardo B.; Shimizu, Yoji; Burkhardt, Janis K.; Freedman, Bruce D.; Billadeau, Daniel D.
2007-01-01
Summary Background The engagement of the T cell receptor results in actin cytoskeletal reorganization at the immune synapse (IS) and the triggering of biochemical signaling cascades leading to gene regulation and, ultimately, cellular activation. Recent studies have identified the WAVE family of proteins as critical mediators of Rac1-induced actin reorganization in other cell types. However, whether these proteins participate in actin reorganization at the IS or signaling pathways in T cells has not been investigated. Results By using a combination of biochemical, genetic, and cell biology approaches, we provide evidence that WAVE2 is recruited to the IS, is biochemically modified, and is required for actin reorganization and β-integrin-mediated adhesion after TCR crosslinking. Moreover, we show that WAVE2 regulates calcium entry at a point distal to PLCγ1 activation and IP3-mediated store release. Conclusions These data reveal a role for WAVE2 in regulating multiple pathways leading to T cell activation. In particular, this work shows that WAVE2 is a key component of the actin regulatory machinery in T cells and that it also participates in linking intracellular calcium store depletion to calcium release-activated calcium (CRAC) channel activation. PMID:16401421
ABI3, a component of the WAVE2 complex, is potentially regulated by PI3K/AKT pathway
Moraes, Lais; Zanchin, Nilson I.T.; Cerutti, Janete M.
2017-01-01
We previously reported that ABI3 expression is lost in follicular thyroid carcinomas and its restoration significantly inhibited cell growth, invasiveness, migration, and reduced tumor growth in vivo. The mechanistic basis by which ABI3 exerts its tumor suppressive effects is not fully understood. In this study, we show that ABI3 is a phosphoprotein. Using proteomic array analysis, we showed that ABI3 modulated distinct cancer-related pathways in thyroid cancer cells. The KEA analysis found that PI3K substrates were enriched and forced expression of ABI3 markedly decreased the phosphorylation of AKT and the downstream-targeted protein pGSK3β. We next used immunoprecipitation combined with mass spectrometry to identify ABI3-interacting proteins that may be involved in modulating/integrating signaling pathways. We identified 37 ABI3 partners, including several components of the canonical WAVE regulatory complex (WRC) such as WAVE2/CYF1P1/NAP1, suggesting that ABI3 function might be regulated through WRC. Both, pharmacological inhibition of the PI3K/AKT pathway and mutation at residue S342 of ABI3, which is predicted to be phosphorylated by AKT, provided evidences that the non-phosphorylated form of ABI3 is preferentially present in the WRC protein complex. Collectively, our findings suggest that ABI3 might be a downstream mediator of the PI3K/AKT pathway that might disrupt WRC via ABI3 phosphorylation. PMID:28978070
ABI3, a component of the WAVE2 complex, is potentially regulated by PI3K/AKT pathway.
Moraes, Lais; Zanchin, Nilson I T; Cerutti, Janete M
2017-09-15
We previously reported that ABI3 expression is lost in follicular thyroid carcinomas and its restoration significantly inhibited cell growth, invasiveness, migration, and reduced tumor growth in vivo . The mechanistic basis by which ABI3 exerts its tumor suppressive effects is not fully understood. In this study, we show that ABI3 is a phosphoprotein. Using proteomic array analysis, we showed that ABI3 modulated distinct cancer-related pathways in thyroid cancer cells. The KEA analysis found that PI3K substrates were enriched and forced expression of ABI3 markedly decreased the phosphorylation of AKT and the downstream-targeted protein pGSK3β. We next used immunoprecipitation combined with mass spectrometry to identify ABI3-interacting proteins that may be involved in modulating/integrating signaling pathways. We identified 37 ABI3 partners, including several components of the canonical WAVE regulatory complex (WRC) such as WAVE2/CYF1P1/NAP1, suggesting that ABI3 function might be regulated through WRC. Both, pharmacological inhibition of the PI3K/AKT pathway and mutation at residue S342 of ABI3, which is predicted to be phosphorylated by AKT, provided evidences that the non-phosphorylated form of ABI3 is preferentially present in the WRC protein complex. Collectively, our findings suggest that ABI3 might be a downstream mediator of the PI3K/AKT pathway that might disrupt WRC via ABI3 phosphorylation.
Roybal, Kole T.; Buck, Taráz E.; Ruan, Xiongtao; Cho, Baek Hwan; Clark, Danielle J.; Ambler, Rachel; Tunbridge, Helen M.; Zhang, Jianwei; Verkade, Paul; Wülfing, Christoph; Murphy, Robert F.
2016-01-01
Fluorescence microscopy is one of the most important tools in cell biology research and it provides spatial and temporal information to investigate regulatory systems inside cells. This technique can generate data in the form of signal intensities at thousands of positions resolved inside individual live cells; however, given extensive cell-to-cell variation, methods do not currently exist to assemble these data into three- or four-dimensional maps of protein concentration that can be compared across different cells and conditions. Here, we have developed one such method and applied it to investigate actin dynamics in T cell activation. Antigen recognition in T cells by the T cell receptor (TCR) is amplified by engagement of the costimulatory receptor CD28 and we have determined how CD28 modulates actin dynamics. We imaged actin and eight core actin regulators under conditions where CD28 in the context of a strong TCR signal was engaged or blocked to yield over a thousand movies. Our computational analysis identified diminished recruitment of the activator of actin nucleation WAVE2 and the actin severing protein cofilin to F-actin as the dominant difference upon costimulation blockade. Reconstitution of WAVE2 and cofilin activity restored the defect in actin signaling dynamics upon costimulation blockade. Thus we have developed and validated an approach to quantify protein distributions in time and space for analysis of complex regulatory systems. PMID:27095595
Lv, Xiaoyang; Sun, Wei; Yin, Jinfeng; Ni, Rong; Su, Rui; Wang, Qingzeng; Gao, Wen; Bao, Jianjun; Yu, Jiarui; Wang, Lihong; Chen, Ling
2016-01-01
Wave patterns in lambskin hair follicles are an important factor determining the quality of sheep’s wool. Hair follicles in lambskin from Hu sheep, a breed unique to China, have 3 types of waves, designated as large, medium, and small. The quality of wool from small wave follicles is excellent, while the quality of large waves is considered poor. Because no molecular and biological studies on hair follicles of these sheep have been conducted to date, the molecular mechanisms underlying the formation of different wave patterns is currently unknown. The aim of this article was to screen the candidate microRNAs (miRNA) and genes for the development of hair follicles in Hu sheep. Two-day-old Hu lambs were selected from full-sib individuals that showed large, medium, and small waves. Integrated analysis of microRNA and mRNA expression profiles employed high-throughout sequencing technology. Approximately 13, 24, and 18 differentially expressed miRNAs were found between small and large waves, small and medium waves, and medium and large waves, respectively. A total of 54, 190, and 81 differentially expressed genes were found between small and large waves, small and medium waves, and medium and large waves, respectively, by RNA sequencing (RNA-seq) analysis. Differentially expressed genes were classified using gene ontology and pathway analyses. They were found to be mainly involved in cell differentiation, proliferation, apoptosis, growth, immune response, and ion transport, and were associated with MAPK and the Notch signaling pathway. Reverse transcription-polymerase chain reaction (RT-PCR) analyses of differentially-expressed miRNA and genes were consistent with sequencing results. Integrated analysis of miRNA and mRNA expression indicated that, compared to small waves, large waves included 4 downregulated miRNAs that had regulatory effects on 8 upregulated genes and 3 upregulated miRNAs, which in turn influenced 13 downregulated genes. Compared to small waves, medium waves included 13 downregulated miRNAs that had regulatory effects on 64 upregulated genes and 4 upregulated miRNAs, which in turn had regulatory effects on 22 downregulated genes. Compared to medium waves, large waves consisted of 13 upregulated miRNAs that had regulatory effects on 48 downregulated genes. These differentially expressed miRNAs and genes may play a significant role in forming different patterns, and provide evidence for the molecular mechanisms underlying the formation of hair follicles of varying patterns. PMID:27404636
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dooher, Brendan; Toman, William I.; Davy, Doug M.
The California Wave Energy Test Center (CalWave) Feasibility Study project was funded over multiple phases by the Department of Energy to perform an interdisciplinary feasibility assessment to analyze the engineering, permitting, and stakeholder requirements to establish an open water, fully energetic, grid connected, wave energy test center off the coast of California for the purposes of advancing U.S. wave energy research, development, and testing capabilities. Work under this grant included wave energy resource characterization, grid impact and interconnection requirements, port infrastructure and maritime industry capability/suitability to accommodate the industry at research, demonstration and commercial scale, and macro and micro sitingmore » considerations. CalWave Phase I performed a macro-siting and down-selection process focusing on two potential test sites in California: Humboldt Bay and Vandenberg Air Force Base. This work resulted in the Vandenberg Air Force Base site being chosen as the most favorable site based on a peer reviewed criteria matrix. CalWave Phase II focused on four siting location alternatives along the Vandenberg Air Force Base coastline and culminated with a final siting down-selection. Key outcomes from this work include completion of preliminary engineering and systems integration work, a robust turnkey cost estimate, shoreside and subsea hazards assessment, storm wave analysis, lessons learned reports from several maritime disciplines, test center benchmarking as compared to existing international test sites, analysis of existing applicable environmental literature, the completion of a preliminary regulatory, permitting and licensing roadmap, robust interaction and engagement with state and federal regulatory agency personnel and local stakeholders, and the population of a Draft Federal Energy Regulatory Commission (FERC) Preliminary Application Document (PAD). Analysis of existing offshore oil and gas infrastructure was also performed to assess the potential value and re-use scenarios of offshore platform infrastructure and associated subsea power cables and shoreside substations. The CalWave project team was well balanced and was comprised of experts from industry, academia, state and federal regulatory agencies. The result of the CalWave feasibility study finds that the CalWave Test Center has the potential to provide the most viable path to commercialization for wave energy in the United States.« less
Testing dispersant effectiveness under conditions similar to that of the open environment is required for improvements in operational procedures and the formulation of regulatory guidelines. To this end, a novel wave tank facility was fabricated to study the dispersion of crude ...
Roybal, Kole T; Buck, Taráz E; Ruan, Xiongtao; Cho, Baek Hwan; Clark, Danielle J; Ambler, Rachel; Tunbridge, Helen M; Zhang, Jianwei; Verkade, Paul; Wülfing, Christoph; Murphy, Robert F
2016-04-19
Fluorescence microscopy is one of the most important tools in cell biology research because it provides spatial and temporal information to investigate regulatory systems inside cells. This technique can generate data in the form of signal intensities at thousands of positions resolved inside individual live cells. However, given extensive cell-to-cell variation, these data cannot be readily assembled into three- or four-dimensional maps of protein concentration that can be compared across different cells and conditions. We have developed a method to enable comparison of imaging data from many cells and applied it to investigate actin dynamics in T cell activation. Antigen recognition in T cells by the T cell receptor (TCR) is amplified by engagement of the costimulatory receptor CD28. We imaged actin and eight core actin regulators to generate over a thousand movies of T cells under conditions in which CD28 was either engaged or blocked in the context of a strong TCR signal. Our computational analysis showed that the primary effect of costimulation blockade was to decrease recruitment of the activator of actin nucleation WAVE2 (Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2) and the actin-severing protein cofilin to F-actin. Reconstitution of WAVE2 and cofilin activity restored the defect in actin signaling dynamics caused by costimulation blockade. Thus, we have developed and validated an approach to quantify protein distributions in time and space for the analysis of complex regulatory systems. Copyright © 2016, American Association for the Advancement of Science.
Hamp, Julia; Löwer, Andreas; Dottermusch-Heidel, Christine; Beck, Lothar; Moussian, Bernard; Flötenmeyer, Matthias
2016-01-01
ABSTRACT The fusion of founder cells and fusion-competent myoblasts (FCMs) is crucial for muscle formation in Drosophila. Characteristic events of myoblast fusion include the recognition and adhesion of myoblasts, and the formation of branched F-actin by the Arp2/3 complex at the site of cell–cell contact. At the ultrastructural level, these events are reflected by the appearance of finger-like protrusions and electron-dense plaques that appear prior to fusion. Severe defects in myoblast fusion are caused by the loss of Kette (a homolog of Nap1 and Hem-2, also known as NCKAP1 and NCKAP1L, respectively), a member of the regulatory complex formed by Scar or WAVE proteins (represented by the single protein, Scar, in flies). kette mutants form finger-like protrusions, but the electron-dense plaques are extended. Here, we show that the electron-dense plaques in wild-type and kette mutant myoblasts resemble other electron-dense structures that are known to function as cellular junctions. Furthermore, analysis of double mutants and attempts to rescue the kette mutant phenotype with N-cadherin, wasp and genes of members of the regulatory Scar complex revealed that Kette has two functions during myoblast fusion. First, Kette controls the dissolution of electron-dense plaques. Second, Kette controls the ratio of the Arp2/3 activators Scar and WASp in FCMs. PMID:27521427
Federal Register 2010, 2011, 2012, 2013, 2014
2010-04-23
... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 12749-002] Oregon Wave...) of the Federal Power Act, proposing to study the feasibility of the Coos Bay OPT Wave Park Project... Comments, Motions To Intervene, and Competing Applications April 16, 2010. On March 2, 2010, Oregon Wave...
Neutrophils establish rapid and robust WAVE complex polarity in an actin-dependent fashion.
Millius, Arthur; Dandekar, Sheel N; Houk, Andrew R; Weiner, Orion D
2009-02-10
Asymmetric intracellular signals enable cells to migrate in response to external cues. The multiprotein WAVE (also known as SCAR or WASF) complex activates the actin-nucleating Arp2/3 complex [1-4] and localizes to propagating "waves," which direct actin assembly during neutrophil migration [5, 6]. Here, we observe similar WAVE complex dynamics in other mammalian cells and analyze WAVE complex dynamics during establishment of neutrophil polarity. Earlier models proposed that spatially biased generation [7] or selection of protrusions [8] enables chemotaxis. These models require existing morphological polarity to control protrusions. We show that spatially biased generation and selection of WAVE complex recruitment also occur in morphologically unpolarized neutrophils during development of their first protrusions. Additionally, several mechanisms limit WAVE complex recruitment during polarization and movement: Intrinsic cues restrict WAVE complex distribution during establishment of polarity, and asymmetric intracellular signals constrain it in morphologically polarized cells. External gradients can overcome both intrinsic biases and control WAVE complex localization. After latrunculin-mediated inhibition of actin polymerization, addition and removal of agonist gradients globally recruits and releases the WAVE complex from the membrane. Under these conditions, the WAVE complex no longer polarizes, despite the presence of strong external gradients. Thus, actin polymer and the WAVE complex reciprocally interact during polarization.
Beaver, Julia A.; Tzou, Abraham; Blumenthal, Gideon M.; McKee, Amy E.; Kim, Geoffrey; Pazdur, Richard; Philip, Reena
2016-01-01
As technologies evolve, and diagnostics move from detection of single biomarkers toward complex signatures, an increase in the clinical use and regulatory submission of complex signatures is anticipated. However, to date, no complex signatures have been approved as companion diagnostics. In this article, we will describe the potential benefit of complex signatures and their unique regulatory challenges including analytical performance validation, complex signature simulation, and clinical performance evaluation. We also will review the potential regulatory pathways for clearance, approval, or acceptance of complex signatures by the U.S. Food and Drug Administration (FDA). These regulatory pathways include regulations applicable to in vitro diagnostic devices, including companion diagnostic devices, the potential for labeling as a complementary diagnostic, and the biomarker qualification program. PMID:27993967
Hafla, Erin; Johnson, Erick; Johnson, C. Nathan; ...
2018-06-01
Marine hydrokinetic (MHK) devices generate electricity from the motion of tidal and ocean currents, as well as ocean waves, to provide an additional source of renewable energy available to the United States. These devices are a source of anthropogenic noise in the marine ecosystem and must meet regulatory guidelines that mandate a maximum amount of noise that may be generated. In the absence of measured levels from in situ deployments, a model for predicting the propagation of sound from an array of MHK sources in a real environment is essential. A set of coupled, linearized velocity-pressure equations in the time-domainmore » are derived and presented in this paper, which are an alternative solution to the Helmholtz and wave equation methods traditionally employed. Discretizing these equations on a three-dimensional (3D), finite-difference grid ultimately permits a finite number of complex sources and spatially varying sound speeds, bathymetry, and bed composition. The solution to this system of equations has been parallelized in an acoustic-wave propagation package developed at Sandia National Labs, called Paracousti. This work presents the broadband sound pressure levels from a single source in two-dimensional (2D) ideal and Pekeris wave-guides and in a 3D domain with a sloping boundary. Furthermore, the paper concludes with demonstration of Paracousti for an array of MHK sources in a simple wave-guide.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hafla, Erin; Johnson, Erick; Johnson, C. Nathan
Marine hydrokinetic (MHK) devices generate electricity from the motion of tidal and ocean currents, as well as ocean waves, to provide an additional source of renewable energy available to the United States. These devices are a source of anthropogenic noise in the marine ecosystem and must meet regulatory guidelines that mandate a maximum amount of noise that may be generated. In the absence of measured levels from in situ deployments, a model for predicting the propagation of sound from an array of MHK sources in a real environment is essential. A set of coupled, linearized velocity-pressure equations in the time-domainmore » are derived and presented in this paper, which are an alternative solution to the Helmholtz and wave equation methods traditionally employed. Discretizing these equations on a three-dimensional (3D), finite-difference grid ultimately permits a finite number of complex sources and spatially varying sound speeds, bathymetry, and bed composition. The solution to this system of equations has been parallelized in an acoustic-wave propagation package developed at Sandia National Labs, called Paracousti. This work presents the broadband sound pressure levels from a single source in two-dimensional (2D) ideal and Pekeris wave-guides and in a 3D domain with a sloping boundary. Furthermore, the paper concludes with demonstration of Paracousti for an array of MHK sources in a simple wave-guide.« less
75 FR 51266 - Reedsport OPT Wave Park, LLC; Notice of Settlement Agreement and Soliciting Comments
Federal Register 2010, 2011, 2012, 2013, 2014
2010-08-19
... 2, 2010. d. Applicant: Reedsport OPT Wave Park, LLC. e. Location: The proposed project would be... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 12713-002] Reedsport OPT Wave Park, LLC; Notice of Settlement Agreement and Soliciting Comments August 10, 2010. Take notice...
Chan, Maia M.; Wooden, Jason M.; Tsang, Mark; Gilligan, Diana M.; Hirenallur-S, Dinesh K.; Finney, Greg L.; Rynes, Eric; MacCoss, Michael; Ramirez, Julita A.; Park, Heon; Iritani, Brian M.
2013-01-01
Hematopoietic protein-1 (Hem-1) is a hematopoietic cell specific member of the WAVE (Wiskott-Aldrich syndrome verprolin-homologous protein) complex, which regulates filamentous actin (F-actin) polymerization in many cell types including immune cells. However, the roles of Hem-1 and the WAVE complex in erythrocyte biology are not known. In this study, we utilized mice lacking Hem-1 expression due to a non-coding point mutation in the Hem1 gene to show that absence of Hem-1 results in microcytic, hypochromic anemia characterized by abnormally shaped erythrocytes with aberrant F-actin foci and decreased lifespan. We find that Hem-1 and members of the associated WAVE complex are normally expressed in wildtype erythrocyte progenitors and mature erythrocytes. Using mass spectrometry and global proteomics, Coomassie staining, and immunoblotting, we find that the absence of Hem-1 results in decreased representation of essential erythrocyte membrane skeletal proteins including α- and β- spectrin, dematin, p55, adducin, ankyrin, tropomodulin 1, band 3, and band 4.1. Hem1−/− erythrocytes exhibit increased protein kinase C-dependent phosphorylation of adducin at Ser724, which targets adducin family members for dissociation from spectrin and actin, and subsequent proteolysis. Increased adducin Ser724 phosphorylation in Hem1−/− erythrocytes correlates with decreased protein expression of the regulatory subunit of protein phosphatase 2A (PP2A), which is required for PP2A-dependent dephosphorylation of PKC targets. These results reveal a novel, critical role for Hem-1 in the homeostasis of structural proteins required for formation and stability of the actin membrane skeleton in erythrocytes. PMID:23424621
Federal Register 2010, 2011, 2012, 2013, 2014
2010-07-06
... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13666-000] Reedsport OPT Wave Park, LLC; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications June 24, 2010. Reedsport OPT Wave Park, LLC filed on...
Federal Register 2010, 2011, 2012, 2013, 2014
2010-12-10
... Office of Energy Projects has reviewed Reedsport OPT Wave Park, LLC's application for license for the Reedsport OPT Wave Park Project (FERC Project No. 12713-002), which would be located in Oregon State... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 12713-002] Reedsport OPT...
Taxi Regulatory Revision in Portland Oregon : Background and Implementation
DOT National Transportation Integrated Search
1980-09-01
The Portland Council has adopted successive waves of taxi regulatory revisions. Effective in Marh, 1979, the previous ceiling on total permits was removed and entry was opened to qualified applicats. The new reulations also provided for flat, discoun...
Millius, Arthur; Watanabe, Naoki; Weiner, Orion D
2012-03-01
The SCAR/WAVE complex drives lamellipodium formation by enhancing actin nucleation by the Arp2/3 complex. Phosphoinositides and Rac activate the SCAR/WAVE complex, but how SCAR/WAVE and Arp2/3 complexes converge at sites of nucleation is unknown. We analyzed the single-molecule dynamics of WAVE2 and p40 (subunits of the SCAR/WAVE and Arp2/3 complexes, respectively) in XTC cells. We observed lateral diffusion of both proteins and captured the transition of p40 from diffusion to network incorporation. These results suggest that a diffusive 2D search facilitates binding of the Arp2/3 complex to actin filaments necessary for nucleation. After nucleation, the Arp2/3 complex integrates into the actin network and undergoes retrograde flow, which results in its broad distribution throughout the lamellipodium. By contrast, the SCAR/WAVE complex is more restricted to the cell periphery. However, with single-molecule imaging, we also observed WAVE2 molecules undergoing retrograde motion. WAVE2 and p40 have nearly identical speeds, lifetimes and sites of network incorporation. Inhibition of actin retrograde flow does not prevent WAVE2 association and disassociation with the membrane but does inhibit WAVE2 removal from the actin cortex. Our results suggest that membrane binding and diffusion expedites the recruitment of nucleation factors to a nucleation site independent of actin assembly, but after network incorporation, ongoing actin polymerization facilitates recycling of SCAR/WAVE and Arp2/3 complexes.
Millius, Arthur; Watanabe, Naoki; Weiner, Orion D.
2012-01-01
The SCAR/WAVE complex drives lamellipodium formation by enhancing actin nucleation by the Arp2/3 complex. Phosphoinositides and Rac activate the SCAR/WAVE complex, but how SCAR/WAVE and Arp2/3 complexes converge at sites of nucleation is unknown. We analyzed the single-molecule dynamics of WAVE2 and p40 (subunits of the SCAR/WAVE and Arp2/3 complexes, respectively) in XTC cells. We observed lateral diffusion of both proteins and captured the transition of p40 from diffusion to network incorporation. These results suggest that a diffusive 2D search facilitates binding of the Arp2/3 complex to actin filaments necessary for nucleation. After nucleation, the Arp2/3 complex integrates into the actin network and undergoes retrograde flow, which results in its broad distribution throughout the lamellipodium. By contrast, the SCAR/WAVE complex is more restricted to the cell periphery. However, with single-molecule imaging, we also observed WAVE2 molecules undergoing retrograde motion. WAVE2 and p40 have nearly identical speeds, lifetimes and sites of network incorporation. Inhibition of actin retrograde flow does not prevent WAVE2 association and disassociation with the membrane but does inhibit WAVE2 removal from the actin cortex. Our results suggest that membrane binding and diffusion expedites the recruitment of nucleation factors to a nucleation site independent of actin assembly, but after network incorporation, ongoing actin polymerization facilitates recycling of SCAR/WAVE and Arp2/3 complexes. PMID:22349699
Suetsugu, Shiro; Kurisu, Shusaku; Oikawa, Tsukasa; Yamazaki, Daisuke; Oda, Atsushi; Takenawa, Tadaomi
2006-05-22
WAVE2 activates the actin-related protein (Arp) 2/3 complex for Rac-induced actin polymerization during lamellipodium formation and exists as a large WAVE2 protein complex with Sra1/PIR121, Nap1, Abi1, and HSPC300. IRSp53 binds to both Rac and Cdc42 and is proposed to link Rac to WAVE2. We found that the knockdown of IRSp53 by RNA interference decreased lamellipodium formation without a decrease in the amount of WAVE2 complex. Localization of WAVE2 at the cell periphery was retained in IRSp53 knockdown cells. Moreover, activated Cdc42 but not Rac weakened the association between WAVE2 and IRSp53. When we measured Arp2/3 activation in vitro, the WAVE2 complex isolated from the membrane fraction of cells was fully active in an IRSp53-dependent manner but WAVE2 isolated from the cytosol was not. Purified WAVE2 and purified WAVE2 complex were activated by IRSp53 in a Rac-dependent manner with PIP(3)-containing liposomes. Therefore, IRSp53 optimizes the activity of the WAVE2 complex in the presence of activated Rac and PIP(3).
Abi1 is essential for the formation and activation of a WAVE2 signalling complex.
Innocenti, Metello; Zucconi, Adriana; Disanza, Andrea; Frittoli, Emanuela; Areces, Liliana B; Steffen, Anika; Stradal, Theresia E B; Di Fiore, Pier Paolo; Carlier, Marie-France; Scita, Giorgio
2004-04-01
WAVE2 belongs to a family of proteins that mediates actin reorganization by relaying signals from Rac to the Arp2/3 complex, resulting in lamellipodia protrusion. WAVE2 displays Arp2/3-dependent actin nucleation activity in vitro, and does not bind directly to Rac. Instead, it forms macromolecular complexes that have been reported to exert both positive and negative modes of regulation. How these complexes are assembled, localized and activated in vivo remains to be established. Here we use tandem mass spectrometry to identify an Abi1-based complex containing WAVE2, Nap1 (Nck-associated protein) and PIR121. Abi1 interacts directly with the WHD domain of WAVE2, increases WAVE2 actin polymerization activity and mediates the assembly of a WAVE2-Abi1-Nap1-PIR121 complex. The WAVE2-Abi1-Nap1-PIR121 complex is as active as the WAVE2-Abi1 sub-complex in stimulating Arp2/3, and after Rac activation it is re-localized to the leading edge of ruffles in vivo. Consistently, inhibition of Abi1 by RNA interference (RNAi) abrogates Rac-dependent lamellipodia protrusion. Thus, Abi1 orchestrates the proper assembly of the WAVE2 complex and mediates its activation at the leading edge in vivo.
Direct-to-digital holography reduction of reference hologram noise and fourier space smearing
Voelkl, Edgar
2006-06-27
Systems and methods are described for reduction of reference hologram noise and reduction of Fourier space smearing, especially in the context of direct-to-digital holography (off-axis interferometry). A method of reducing reference hologram noise includes: recording a plurality of reference holograms; processing the plurality of reference holograms into a corresponding plurality of reference image waves; and transforming the corresponding plurality of reference image waves into a reduced noise reference image wave. A method of reducing smearing in Fourier space includes: recording a plurality of reference holograms; processing the plurality of reference holograms into a corresponding plurality of reference complex image waves; transforming the corresponding plurality of reference image waves into a reduced noise reference complex image wave; recording a hologram of an object; processing the hologram of the object into an object complex image wave; and dividing the complex image wave of the object by the reduced noise reference complex image wave to obtain a reduced smearing object complex image wave.
Optimization of WAVE2 complex–induced actin polymerization by membrane-bound IRSp53, PIP3, and Rac
Suetsugu, Shiro; Kurisu, Shusaku; Oikawa, Tsukasa; Yamazaki, Daisuke; Oda, Atsushi; Takenawa, Tadaomi
2006-01-01
WAVE2 activates the actin-related protein (Arp) 2/3 complex for Rac-induced actin polymerization during lamellipodium formation and exists as a large WAVE2 protein complex with Sra1/PIR121, Nap1, Abi1, and HSPC300. IRSp53 binds to both Rac and Cdc42 and is proposed to link Rac to WAVE2. We found that the knockdown of IRSp53 by RNA interference decreased lamellipodium formation without a decrease in the amount of WAVE2 complex. Localization of WAVE2 at the cell periphery was retained in IRSp53 knockdown cells. Moreover, activated Cdc42 but not Rac weakened the association between WAVE2 and IRSp53. When we measured Arp2/3 activation in vitro, the WAVE2 complex isolated from the membrane fraction of cells was fully active in an IRSp53-dependent manner but WAVE2 isolated from the cytosol was not. Purified WAVE2 and purified WAVE2 complex were activated by IRSp53 in a Rac-dependent manner with PIP3-containing liposomes. Therefore, IRSp53 optimizes the activity of the WAVE2 complex in the presence of activated Rac and PIP3. PMID:16702231
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2012-10-29
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Controls of multi-modal wave conditions in a complex coastal setting
Hegermiller, Christie; Rueda, Ana C.; Erikson, Li H.; Barnard, Patrick L.; Antolinez, J.A.A.; Mendez, Fernando J.
2017-01-01
Coastal hazards emerge from the combined effect of wave conditions and sea level anomalies associated with storms or low-frequency atmosphere-ocean oscillations. Rigorous characterization of wave climate is limited by the availability of spectral wave observations, the computational cost of dynamical simulations, and the ability to link wave-generating atmospheric patterns with coastal conditions. We present a hybrid statistical-dynamical approach to simulating nearshore wave climate in complex coastal settings, demonstrated in the Southern California Bight, where waves arriving from distant, disparate locations are refracted over complex bathymetry and shadowed by offshore islands. Contributions of wave families and large-scale atmospheric drivers to nearshore wave energy flux are analyzed. Results highlight the variability of influences controlling wave conditions along neighboring coastlines. The universal method demonstrated here can be applied to complex coastal settings worldwide, facilitating analysis of the effects of climate change on nearshore wave climate.
Controls of Multimodal Wave Conditions in a Complex Coastal Setting
NASA Astrophysics Data System (ADS)
Hegermiller, C. A.; Rueda, A.; Erikson, L. H.; Barnard, P. L.; Antolinez, J. A. A.; Mendez, F. J.
2017-12-01
Coastal hazards emerge from the combined effect of wave conditions and sea level anomalies associated with storms or low-frequency atmosphere-ocean oscillations. Rigorous characterization of wave climate is limited by the availability of spectral wave observations, the computational cost of dynamical simulations, and the ability to link wave-generating atmospheric patterns with coastal conditions. We present a hybrid statistical-dynamical approach to simulating nearshore wave climate in complex coastal settings, demonstrated in the Southern California Bight, where waves arriving from distant, disparate locations are refracted over complex bathymetry and shadowed by offshore islands. Contributions of wave families and large-scale atmospheric drivers to nearshore wave energy flux are analyzed. Results highlight the variability of influences controlling wave conditions along neighboring coastlines. The universal method demonstrated here can be applied to complex coastal settings worldwide, facilitating analysis of the effects of climate change on nearshore wave climate.
c-Abl interacts with the WAVE2 signaling complex to induce membrane ruffling and cell spreading.
Stuart, Jeremy R; Gonzalez, Francis H; Kawai, Hidehiko; Yuan, Zhi-Min
2006-10-20
The Wiskott-Aldrich syndrome-related protein WAVE2 promotes Arp2/3-dependent actin polymerization downstream of Rho-GTPase activation. The Abelson-interacting protein-1 (Abi-1) forms the core of the WAVE2 complex and is necessary for proper stimulation of WAVE2 activity. Here we have shown that the Abl-tyrosine kinase interacts with the WAVE2 complex and that Abl kinase activity facilitates interaction between Abl and WAVE2 complex members. We have characterized various interactions between Abl and members of the WAVE2 complex and revealed that Abi-1 promotes interaction between Abl and WAVE2 members. We have demonstrated that Abl-dependent phosphorylation of WAVE2 is necessary for its activation in vivo, which is highlighted by the findings that RNA interference of WAVE2 expression in Abl/Arg-/- cells has no additive effect on the amount of membrane ruffling. Furthermore, Abl phosphorylates WAVE2 on tyrosine 150, and WAVE2-deficient cells rescued with a Y150F mutant fail to regain their ability to ruffle and form microspikes, unlike cells rescued with wild-type WAVE2. Together, these data show that c-Abl activates WAVE2 via tyrosine phosphorylation to promote actin remodeling in vivo and that Abi-1 forms the crucial link between these two factors.
WAVE2 signaling mediates invasion of polarized epithelial cells by Salmonella typhimurium.
Shi, Jing; Scita, Giorgio; Casanova, James E
2005-08-19
The bacterial pathogen Salmonella penetrates the intestinal epithelium by inducing its own phagocytosis into epithelial cells. The dramatic reorganization of the actin cytoskeleton required for internalization is driven by bacterial manipulation of host signaling pathways, including activation of the Rho family GTPase Rac1 and subsequent activation of the Arp2/3 complex. However, the mechanisms linking these two events remain poorly understood. Rac1 is thought to promote activation of the Arp2/3 complex through its interaction with suppressor of cAMP receptor/WASP family verprolin-homologous (SCAR/WAVE) family proteins, but this interaction is apparently indirect. Two different Rac1 effectors have been shown to bind WAVE2: IRSp53, the SH3 domain of which binds the WAVE2 proline-rich domain, and PIR121/Sra-1, which forms a pentameric complex containing WAVE, Abi1, Nap1, and HSPC300. However, the extent to which each of these complexes contributes to Arp2/3 complex activation in the context of Salmonella infection is unclear. Here, we show that WAVE2 is necessary for efficient invasion of epithelial cells by Salmonella typhimurium. We found that although Salmonella infection strongly promotes the formation of an IRSp53/WAVE2 complex, IRSp53 is not necessary for bacterial internalization. In contrast, disruption of the PIR121/Nap1/Abi1/WAVE2/HSPC300 complex potently inhibits bacterial uptake. These results indicate that WAVE2 is an important component in signaling pathways leading to Salmonella invasion. Although infection leads to the formation of an IRSp53/WAVE2 complex, it is the association of WAVE2 with the Abi1/Nap1/PIR121/HSPC300 complex that regulates bacterial internalization.
Stephan, Raiko; Gohl, Christina; Fleige, Astrid; Klämbt, Christian; Bogdan, Sven
2011-01-01
A tight spatial-temporal coordination of F-actin dynamics is crucial for a large variety of cellular processes that shape cells. The Abelson interactor (Abi) has a conserved role in Arp2/3-dependent actin polymerization, regulating Wiskott-Aldrich syndrome protein (WASP) and WASP family verprolin-homologous protein (WAVE). In this paper, we report that Abi exerts nonautonomous control of photoreceptor axon targeting in the Drosophila visual system through WAVE. In abi mutants, WAVE is unstable but restored by reexpression of Abi, confirming that Abi controls the integrity of the WAVE complex in vivo. Remarkably, expression of a membrane-tethered WAVE protein rescues the axonal projection defects of abi mutants in the absence of the other subunits of the WAVE complex, whereas cytoplasmic WAVE only slightly affects the abi mutant phenotype. Thus complex formation not only stabilizes WAVE, but also provides further membrane-recruiting signals, resulting in an activation of WAVE. PMID:21900504
[The extraction and analysis of a- and b- wave from electroretinogram in human].
Chen, Zi-he; Zheng, Chang-wei; Lei, Bo
2013-12-01
To determine the frequency range of a-b wave complex in the dark- and light-adapted electroretinogram (ERG) and to isolate the pure a- and b- waves. Case series study. Full-field ERGs were recorded in 16 eyes of 8 normal volunteers from October to November 2011. Digital filtering technique was used to extract the a- and b-waves from dark- and light-adapted ERG responses. The timings of a- and b-wave were measured to determine the frequency range of a-b wave complex. Major frequency components were determined from power spectra using fast Fourier transform (FFT). The effect of different order settings in the digital filter were compared to investigate the optimum condition, where the oscillatory potential (OP) was completely removed while the amplitudes and phases of the a- and b- waves were less affected. The Student-t test was used to compare the frequency range of a-b wave complex in dark- and light-adapted ERG. The averaged frequency range of the dark-adapted a-b wave complex was from (14.99 ± 2.39) to (25.35 ± 3.77) Hz, compared with (25.22 ± 6.56) to (32.47 ± 3.68) Hz for the light-adapted a-b wave complex, respectively, indicating the frequency range of the dark-adapted a-b wave complex was significantly less than the light-adapted a-b wave complex (t = 7.910, 7.693; both P < 0.01). The third order of the digital filter and a passband of 1 to 45 Hz was the best choice in term of removing the high frequency OP from the waveform of ERG and keeping the amplitude and phase of the a- and b- waves. The frequency of a-b wave complex is lower than that of OP. Therefore the a- and b- waves can be isolated from OP using different digital filter settings in human ERG. A third order and a passband of 1 to 45 Hz is the best choice to extract pure a- and b- waves from the original ERG.
NASA Technical Reports Server (NTRS)
Hovenac, Edward A.; Lock, James A.
1991-01-01
The contributions of complex rays and the secondary radiation shed by surface waves to scattering by a dielectric sphere are calculated in the context of the Debye series expansion of the Mie scattering amplitudes. Also, the contributions of geometrical rays are reviewed and compared with the Debye series. Interference effects between surface waves, complex waves, and geometrical waves are calculated, and the possibility of observing these interference effects is discussed. Experimental data supporting the observation of a surface wave-geometrical pattern is presented.
Effect of WAVE2 phosphorylation on activation of the Arp2/3 complex.
Nakanishi, Osamu; Suetsugu, Shiro; Yamazaki, Daisuke; Takenawa, Tadaomi
2007-03-01
Members of the family of WASP-family Verprolin homologous proteins (WAVEs) activate the Arp2/3 complex to induce actin polymerization. The WAVE family comprises three proteins, namely, WAVE1, WAVE2 and WAVE3. Among them, WAVE2 is crucial for activation of the Arp2/3 complex for the formation of branched actin filaments in lamellipodia. Activation of mitogen-activated protein (MAP) kinase signalling results in the phosphorylation of the WAVE family proteins; however, which of the three WAVE proteins is phosphorylated is unclear. We found that in vitro WAVE2 is directly phosphorylated by a MAP kinase, i.e. extracellular signal-regulated kinase (ERK) 2. The proline-rich region and the verprolin, cofilin and acidic (VCA) region of WAVE2 were phosphorylated. Interestingly, the phosphorylated VCA region had a higher affinity for the Arp2/3 complex. However, the phosphorylation of the VCA region resulted in reduced induction of Arp2/3-mediated actin polymerization in vitro. The role of the phosphorylation of the proline-rich region was not determined.
Howard, Thomas P; Lloyd, Julie C; Raines, Christine A
2011-07-01
In darkened leaves the Calvin cycle enzymes glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and phosphoribulokinase (PRK) form a regulatory multi-enzyme complex with the small chloroplast protein CP12. GAPDH also forms a high molecular weight regulatory mono-enzyme complex. Given that there are different reports as to the number and subunit composition of these complexes and that enzyme regulatory mechanisms are known to vary between species, it was reasoned that protein-protein interactions may also vary between species. Here, this variation is investigated. This study shows that two different tetramers of GAPDH (an A2B2 heterotetramer and an A4 homotetramer) have the capacity to form part of the PRK/GAPDH/CP12 complex. The role of the PRK/GAPDH/CP12 complex is not simply to regulate the 'non-regulatory' A4 GAPDH tetramer. This study also demonstrates that the abundance and nature of PRK/GAPDH/CP12 interactions are not equal in all species and that whilst NAD enhances complex formation in some species, this is not sufficient for complex formation in others. Furthermore, it is shown that the GAPDH mono-enzyme complex is more abundant as a 2(A2B2) complex, rather than the larger 4(A2B2) complex. This smaller complex is sensitive to cellular metabolites indicating that it is an important regulatory isoform of GAPDH. This comparative study has highlighted considerable heterogeneity in PRK and GAPDH protein interactions between closely related species and the possible underlying physiological basis for this is discussed.
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Role of antisense RNAs in evolution of yeast regulatory complexity.
Lin, Chih-Hsu; Tsai, Zing Tsung-Yeh; Wang, Daryi
2013-01-01
Antisense RNAs (asRNAs) are known to regulate gene expression. However, a genome-wide mechanism of asRNA regulation is unclear, and there is no good explanation why partial asRNAs are not functional. To explore its regulatory role, we investigated asRNAs using an evolutionary approach, as genome-wide experimental data are limited. We found that the percentage of genes coupling with asRNAs in Saccharomyces cerevisiae is negatively associated with regulatory complexity and evolutionary age. Nevertheless, asRNAs evolve more slowly when their sense genes are under more complex regulation. Older genes coupling with asRNAs are more likely to demonstrate inverse expression, reflecting the role of these asRNAs as repressors. Our analyses provide novel evidence, suggesting a minor contribution of asRNAs in developing regulatory complexity. Although our results support the leaky hypothesis for asRNA transcription, our evidence also suggests that partial asRNAs may have evolved as repressors. Our study deepens the understanding of asRNA regulatory evolution. Copyright © 2013 Elsevier Inc. All rights reserved.
USDA-ARS?s Scientific Manuscript database
Serine acetyltransferase (SAT) catalyzes the limiting reaction in plant and microbial biosynthesis of cysteine. In addition to its enzymatic function, SAT forms a macromolecular complex with O-acetylserine sulfhydrylase (OASS). Formation of the cysteine regulatory complex (CRC) is a critical biochem...
A novel role for WAVE1 in controlling actin network growth rate and architecture
Sweeney, Meredith O.; Collins, Agnieszka; Padrick, Shae B.; Goode, Bruce L.
2015-01-01
Branched actin filament networks in cells are assembled through the combined activities of Arp2/3 complex and different WASP/WAVE proteins. Here we used TIRF and electron microscopy to directly compare for the first time the assembly kinetics and architectures of actin filament networks produced by Arp2/3 complex and dimerized VCA regions of WAVE1, WAVE2, or N-WASP. WAVE1 produced strikingly different networks from WAVE2 or N-WASP, which comprised unexpectedly short filaments. Further analysis showed that the WAVE1-specific activity stemmed from an inhibitory effect on filament elongation both in the presence and absence of Arp2/3 complex, which was observed even at low stoichiometries of WAVE1 to actin monomers, precluding an effect from monomer sequestration. Using a series of VCA chimeras, we mapped the elongation inhibitory effects of WAVE1 to its WH2 (“V”) domain. Further, mutating a single conserved lysine residue potently disrupted WAVE1's inhibitory effects. Taken together, our results show that WAVE1 has unique activities independent of Arp2/3 complex that can govern both the growth rates and architectures of actin filament networks. Such activities may underlie previously observed differences between the cellular functions of WAVE1 and WAVE2. PMID:25473116
Cellular and chemical neuroscience of mammalian sleep.
Datta, Subimal
2010-05-01
Extraordinary strides have been made toward understanding the complexities and regulatory mechanisms of sleep over the past two decades thanks to the help of rapidly evolving technologies. At its most basic level, mammalian sleep is a restorative process of the brain and body. Beyond its primary restorative purpose, sleep is essential for a number of vital functions. Our primary research interest is to understand the cellular and molecular mechanisms underlying the regulation of sleep and its cognitive functions. Here I will reflect on our own research contributions to 50 years of extraordinary advances in the neurobiology of slow-wave sleep (SWS) and rapid eye movement (REM) sleep regulation. I conclude this review by suggesting some potential future directions to further our understanding of the neurobiology of sleep. Copyright 2010 Elsevier B.V. All rights reserved.
Harris, Daniel L; Rovere, Alessio; Casella, Elisa; Power, Hannah; Canavesio, Remy; Collin, Antoine; Pomeroy, Andrew; Webster, Jody M; Parravicini, Valeriano
2018-02-01
Coral reefs are diverse ecosystems that support millions of people worldwide by providing coastal protection from waves. Climate change and human impacts are leading to degraded coral reefs and to rising sea levels, posing concerns for the protection of tropical coastal regions in the near future. We use a wave dissipation model calibrated with empirical wave data to calculate the future increase of back-reef wave height. We show that, in the near future, the structural complexity of coral reefs is more important than sea-level rise in determining the coastal protection provided by coral reefs from average waves. We also show that a significant increase in average wave heights could occur at present sea level if there is sustained degradation of benthic structural complexity. Our results highlight that maintaining the structural complexity of coral reefs is key to ensure coastal protection on tropical coastlines in the future.
Harris, Daniel L.; Rovere, Alessio; Casella, Elisa; Power, Hannah; Canavesio, Remy; Collin, Antoine; Pomeroy, Andrew; Webster, Jody M.; Parravicini, Valeriano
2018-01-01
Coral reefs are diverse ecosystems that support millions of people worldwide by providing coastal protection from waves. Climate change and human impacts are leading to degraded coral reefs and to rising sea levels, posing concerns for the protection of tropical coastal regions in the near future. We use a wave dissipation model calibrated with empirical wave data to calculate the future increase of back-reef wave height. We show that, in the near future, the structural complexity of coral reefs is more important than sea-level rise in determining the coastal protection provided by coral reefs from average waves. We also show that a significant increase in average wave heights could occur at present sea level if there is sustained degradation of benthic structural complexity. Our results highlight that maintaining the structural complexity of coral reefs is key to ensure coastal protection on tropical coastlines in the future. PMID:29503866
Yong, Hua-Hie; Hitchman, Sara C; Cummings, K Michael; Borland, Ron; Gravely, Shannon M L; McNeill, Ann; Fong, Geoffrey T
2017-11-01
To date, no studies have explored how different regulatory environments may influence the effectiveness of electronic cigarettes (ECs) as a smoking cessation aid. This study compares the real-world effectiveness of adult smokers using ECs for quitting compared with quitting unassisted or quitting with nicotine replacement therapy (NRT) and/or prescription medications in two countries with restrictive policies towards ECs (ie, Canada and Australia) versus two countries with less restrictive policies (ie, United States and United Kingdom). Data were drawn from the International Tobacco Control Four Country surveys, from the United States and Canada (2 waves, n = 318 and 380, respectively), the United Kingdom (3 waves, n = 439) and Australia (4 waves, n = 662), collected 2010-2014. Smokers at baseline wave who reported making a quit attempt at follow-up were included. The primary outcome was self-reported abstinence for at least 30 days regardless of smoking status at follow-up assessment. Data across waves were combined and analyzed using generalized estimating equations. Compared to unassisted quitting (ie, no medications or ECs), smokers who used ECs for quitting from countries with less restrictive EC policy environments were more likely (OR = 1.95, 95%CI = 1.19-3.20, p < .01), whereas smokers who used ECs for quitting from countries with more restrictive EC policies were less likely (OR = 0.36, 95%CI = 0.18-0.72, p < .01), to report sustained abstinence for at least 30 days. Use of ECs in the real world during a quit attempt appears only effective for sustaining smoking abstinence in a less restrictive EC environment suggesting that the benefits of ECs for smoking cessation are likely highly dependent on the regulatory environment. What this study adds: This is the first study to examine the impact of regulatory environment for ECs on their real-world effectiveness for smoking cessation. This study shows that in a less restrictive EC regulatory environment, use of ECs during a quit attempt facilitates, but in a more restrictive environment, it inhibits, short-term sustained abstinence. The findings underscore the need for careful consideration on how best to regulate this emerging product so that EC benefits for smoking cessation are maximized and its risks to public health are minimized. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.
The anomalous amplification of M2 tide in the Taiwan Strait
NASA Astrophysics Data System (ADS)
Jan, Sen; Chern, Ching-Sheng; Wang, Joe; Chao, Shenn-Yu
2004-04-01
The complex tidal wave propagation pattern in the Taiwan Strait invites parochialism. Along the eastern (Taiwan) boundary of the strait, the anomalous amplification of M2 tide in the middle often led to the parochial view that two tidal waves coming from both ends of the strait collide in the middle, creating wave resonance. Along the western (China) boundary, one sees a southward progressive tidal wave and hence no wave collision. To reconcile, we examine a few solutions of a numerical tidal model below. Both realistic bottom bathymetry and idealized bottom topographies are used to identify dominant mechanism leading to the complex tidal wave propagation. Our process of elimination identifies the wave reflection of southward propagating tidal wave by the deep trench in the southern strait as the true cause responsible for the complex wave propagation pattern.
Disentangling the many layers of eukaryotic transcriptional regulation.
Lelli, Katherine M; Slattery, Matthew; Mann, Richard S
2012-01-01
Regulation of gene expression in eukaryotes is an extremely complex process. In this review, we break down several critical steps, emphasizing new data and techniques that have expanded current gene regulatory models. We begin at the level of DNA sequence where cis-regulatory modules (CRMs) provide important regulatory information in the form of transcription factor (TF) binding sites. In this respect, CRMs function as instructional platforms for the assembly of gene regulatory complexes. We discuss multiple mechanisms controlling complex assembly, including cooperative DNA binding, combinatorial codes, and CRM architecture. The second section of this review places CRM assembly in the context of nucleosomes and condensed chromatin. We discuss how DNA accessibility and histone modifications contribute to TF function. Lastly, new advances in chromosomal mapping techniques have provided increased understanding of intra- and interchromosomal interactions. We discuss how these topological maps influence gene regulatory models.
Regulatory challenges and approaches to characterize nanomedicines and their follow-on similars.
Mühlebach, Stefan; Borchard, Gerrit; Yildiz, Selcan
2015-03-01
Nanomedicines are highly complex products and are the result of difficult to control manufacturing processes. Nonbiological complex drugs and their biological counterparts can comprise nanoparticles and therefore show nanomedicine characteristics. They consist of not fully known nonhomomolecular structures, and can therefore not be characterized by physicochemical means only. Also, intended copies of nanomedicines (follow-on similars) may have clinically meaningful differences, creating the regulatory challenge of how to grant a high degree of assurance for patients' benefit and safety. As an example, the current regulatory approach for marketing authorization of intended copies of nonbiological complex drugs appears inappropriate; also, a valid strategy incorporating the complexity of such systems is undefined. To demonstrate sufficient similarity and comparability, a stepwise quality, nonclinical and clinical approach is necessary to obtain market authorization for follow-on products as therapeutic alternatives, substitution and/or interchangeable products. To fill the regulatory gap, harmonized and science-based standards are needed.
WAVE2 forms a complex with PKA and is involved in PKA enhancement of membrane protrusions.
Yamashita, Hiroshi; Ueda, Kazumitsu; Kioka, Noriyuki
2011-02-04
PKA contributes to many physiological processes, including glucose homeostasis and cell migration. The substrate specificity of PKA is low compared with other kinases; thus, complex formation with A-kinase-anchoring proteins is important for the localization of PKA in specific subcellular regions and the phosphorylation of specific substrates. Here, we show that PKA forms a complex with WAVE2 (Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2) in MDA-MB-231 breast cancer cells and mouse brain extracts. Two separate regions of WAVE2 are involved in WAVE2-PKA complex formation. This complex localizes to the leading edge of MDA-MB-231 cells. PKA activation results in enlargement of the membrane protrusion. WAVE2 depletion impairs PKA localization at membrane protrusions and the enlargement of membrane protrusion induced by PKA activation. Together, these results suggest that WAVE2 works as an A-kinase-anchoring protein that recruits PKA at membrane protrusions and plays a role in the enlargement of membrane protrusions induced by PKA activation.
Takahashi, Kazuhide; Suzuki, Katsuo
2009-05-01
Membrane transport of WAVE2 that leads to lamellipodia formation requires a small GTPase Rac1, the motor protein kinesin, and microtubules. Here we explore the possibility of whether the Rac1-dependent and kinesin-mediated WAVE2 transport along microtubules is regulated by a p21-activated kinase Pak as a downstream effector of Rac1. We find that Pak1 constitutively binds to WAVE2 and is transported with WAVE2 to the leading edge by stimulation with hepatocyte growth factor (HGF). Concomitantly, phosphorylation of tubulin-bound stathmin/Op18 at serine 25 (Ser25) and Ser38, microtubule growth, and stathmin/Op18 binding to kinesin-WAVE2 complex were induced. The HGF-induced WAVE2 transport, lamellipodia formation, stathmin/Op18 phosphorylation at Ser38 and binding to kinesin-WAVE2 complex, but not stathmin/Op18 phosphorylation at Ser25 and microtubule growth, were abrogated by Pak1 inhibitor IPA-3 and Pak1 depletion with small interfering RNA (siRNA). Moreover, stathmin/Op18 depletion with siRNA caused significant inhibition of HGF-induced WAVE2 transport and lamellipodia formation, with HGF-independent promotion of microtubule growth. Collectively, it is suggested that Pak1 plays a critical role in HGF-induced WAVE2 transport and lamellipodia formation by directing Pak1-WAVE2-kinesin complex toward the ends of growing microtubules through phosphorylation and recruitment of tubulin-bound stathmin/Op18 to the complex.
Davidson, Andrew J; Insall, Robert H
2013-11-01
The SCAR/WAVE complex drives the actin polymerisation that underlies protrusion of the front of the cell and thus drives migration. However, it is not understood how the activity of SCAR/WAVE is regulated to generate the infinite range of cellular shape changes observed during cell motility. What are the relative roles of the subunits of the SCAR/WAVE complex? What signaling molecules do they interact with? And how does the complex integrate all this information in order to control the temporal and spatial polymerisation of actin during protrusion formation? Unfortunately, the interdependence of SCAR complex members has made genetic dissection hard. In our recent paper,(1) we describe stabilization of the Dictyostelium SCAR complex by a small fragment of Abi. Here we summarize the main findings and discuss how this approach can help reveal the inner workings of this impenetrable complex.
Zhu, Zengrong; Bhat, Krishna Moorthi
2011-01-01
In the nervous system, neurons form in different regions, then they migrate and occupy specific positions. We have previously shown that RP2/sib, a well-studied neuronal pair in the Drosophila ventral nerve cord (VNC), has a complex migration route. Here, we show that the Hem protein, via the WAVE complex, regulates migration of GMC-1 and its progeny RP2 neuron. In Hem or WAVE mutants, RP2 neuron either abnormally migrates, crossing the midline from one hemisegment to the contralateral hemisegment, or does not migrate at al and fail to send out its axon projection. We report that Hem regulates neuronal migration through stabilizing WAVE. Since Hem and WAVE normally form a complex, our data argues that in the absence of Hem, WAVE, which is presumably no longer in a complex, becomes susceptible to degradation. We also find that Abelson Tyrosine kinase affects RP2 migration in a similar manner as Hem and WAVE, and appears to operate via WAVE. However, while Abl negatively regulates the levels of WAVE, it regulates migration via regulating the activity of WAVE. Our results also show that during the degradation of WAVE, Hem function is opposite to that of and downstream of Abl. PMID:21726548
Phenotypic Analysis Reveals that the 2010 Haiti Cholera Epidemic Is Linked to a Hypervirulent Strain
Jones, Christopher J.; Wong, Jennifer; Queen, Jessica; Agarwal, Shivani; Yildiz, Fitnat H.
2016-01-01
Vibrio cholerae O1 El Tor strains have been responsible for pandemic cholera since 1961. These strains have evolved over time, spreading globally in three separate waves. Wave 3 is caused by altered El Tor (AET) variant strains, which include the strain with the signature ctxB7 allele that was introduced in 2010 into Haiti, where it caused a devastating epidemic. In this study, we used phenotypic analysis to compare an early isolate from the Haiti epidemic to wave 1 El Tor isolates commonly used for research. It is demonstrated that the Haiti isolate has increased production of cholera toxin (CT) and hemolysin, increased motility, and a reduced ability to form biofilms. This strain also outcompetes common wave 1 El Tor isolates for colonization of infant mice, indicating that it has increased virulence. Monitoring of CT production and motility in additional wave 3 isolates revealed that this phenotypic variation likely evolved over time rather than in a single genetic event. Analysis of available whole-genome sequences and phylogenetic analyses suggested that increased virulence arose from positive selection for mutations found in known and putative regulatory genes, including hns and vieA, diguanylate cyclase genes, and genes belonging to the lysR and gntR regulatory families. Overall, the studies presented here revealed that V. cholerae virulence potential can evolve and that the currently prevalent wave 3 AET strains are both phenotypically distinct from and more virulent than many El Tor isolates. PMID:27297393
Essential role for Abi1 in embryonic survival and WAVE2 complex integrity.
Dubielecka, Patrycja M; Ladwein, Kathrin I; Xiong, Xiaoling; Migeotte, Isabelle; Chorzalska, Anna; Anderson, Kathryn V; Sawicki, Janet A; Rottner, Klemens; Stradal, Theresia E; Kotula, Leszek
2011-04-26
Abl interactor 1 (Abi1) plays a critical function in actin cytoskeleton dynamics through participation in the WAVE2 complex. To gain a better understanding of the specific role of Abi1, we generated a conditional Abi1-KO mouse model and MEFs lacking Abi1 expression. Abi1-KO cells displayed defective regulation of the actin cytoskeleton, and this dysregulation was ascribed to altered activity of the WAVE2 complex. Changes in motility of Abi1-KO cells were manifested by a decreased migration rate and distance but increased directional persistence. Although these phenotypes did not correlate with peripheral ruffling, which was unaffected, Abi1-KO cells exhibited decreased dorsal ruffling. Western blotting analysis of Abi1-KO cell lysates indicated reduced levels of the WAVE complex components WAVE1 and WAVE2, Nap1, and Sra-1/PIR121. Although relative Abi2 levels were more than doubled in Abi1-KO cells, the absolute Abi2 expression in these cells amounted only to a fifth of Abi1 levels in the control cell line. This finding suggests that the presence of Abi1 is critical for the integrity and stability of WAVE complex and that Abi2 levels are not sufficiently increased to compensate fully for the loss of Abi1 in KO cells and to restore the integrity and function of the WAVE complex. The essential function of Abi1 in WAVE complexes and their regulation might explain the observed embryonic lethality of Abi1-deficient embryos, which survived until approximately embryonic day 11.5 and displayed malformations in the developing heart and brain. Cells lacking Abi1 and the conditional Abi1-KO mouse will serve as critical models for defining Abi1 function.
Essential role for Abi1 in embryonic survival and WAVE2 complex integrity
Dubielecka, Patrycja M.; Ladwein, Kathrin I.; Xiong, Xiaoling; Migeotte, Isabelle; Chorzalska, Anna; Anderson, Kathryn V.; Sawicki, Janet A.; Rottner, Klemens; Stradal, Theresia E.; Kotula, Leszek
2011-01-01
Abl interactor 1 (Abi1) plays a critical function in actin cytoskeleton dynamics through participation in the WAVE2 complex. To gain a better understanding of the specific role of Abi1, we generated a conditional Abi1-KO mouse model and MEFs lacking Abi1 expression. Abi1-KO cells displayed defective regulation of the actin cytoskeleton, and this dysregulation was ascribed to altered activity of the WAVE2 complex. Changes in motility of Abi1-KO cells were manifested by a decreased migration rate and distance but increased directional persistence. Although these phenotypes did not correlate with peripheral ruffling, which was unaffected, Abi1-KO cells exhibited decreased dorsal ruffling. Western blotting analysis of Abi1-KO cell lysates indicated reduced levels of the WAVE complex components WAVE1 and WAVE2, Nap1, and Sra-1/PIR121. Although relative Abi2 levels were more than doubled in Abi1-KO cells, the absolute Abi2 expression in these cells amounted only to a fifth of Abi1 levels in the control cell line. This finding suggests that the presence of Abi1 is critical for the integrity and stability of WAVE complex and that Abi2 levels are not sufficiently increased to compensate fully for the loss of Abi1 in KO cells and to restore the integrity and function of the WAVE complex. The essential function of Abi1 in WAVE complexes and their regulation might explain the observed embryonic lethality of Abi1-deficient embryos, which survived until approximately embryonic day 11.5 and displayed malformations in the developing heart and brain. Cells lacking Abi1 and the conditional Abi1-KO mouse will serve as critical models for defining Abi1 function. PMID:21482783
Kastberger, Gerald; Weihmann, Frank; Hoetzl, Thomas
2010-03-01
The social waves in giant honeybees termed as shimmering are more complex than mexican waves. it has been demonstrated1 that shimmering is triggered by special agents at the nest surface. in this paper, we have used a nest that originated by amalgamation of two previously separated nests and stimulated waves by a dummy wasp moved on a miniature cable car. we illustrate the plausibility of the special-agent hypothesis1 also for complex shimmering processes.
Weihmann, Frank; Hoetzl, Thomas
2010-01-01
The social waves in giant honeybees termed as shimmering are more complex than mexican waves. it has been demonstrated1 that shimmering is triggered by special agents at the nest surface. in this paper, we have used a nest that originated by amalgamation of two previously separated nests and stimulated waves by a dummy wasp moved on a miniature cable car. we illustrate the plausibility of the special-agent hypothesis1 also for complex shimmering processes. PMID:20585516
The NESH/Abi-3-based WAVE2 complex is functionally distinct from the Abi-1-based WAVE2 complex.
Sekino, Saki; Kashiwagi, Yuriko; Kanazawa, Hitoshi; Takada, Kazuki; Baba, Takashi; Sato, Seiichi; Inoue, Hiroki; Kojima, Masaki; Tani, Katsuko
2015-10-01
Abl interactor (Abi) family proteins play significant roles in actin cytoskeleton organization through participation in the WAVE complex. Mammals possess three Abi proteins: Abi-1, Abi-2, and NESH/Abi-3. Abi-1 and Abi-2 were originally identified as Abl tyrosine kinase-binding proteins. It has been disclosed that Abi-1 acts as a bridge between c-Abl and WAVE2, and c-Abl-mediated WAVE2 phosphorylation promotes actin remodeling. We showed previously that NESH/Abi-3 is present in the WAVE2 complex, but neither binds to c-Abl nor promotes c-Abl-mediated phosphorylation of WAVE2. In this study, we characterized NESH/Abi-3 in more detail, and compared its properties with those of Abi-1 and Abi-2. NESH/Abi-3 was ectopically expressed in NIH3T3 cells, in which Abi-1, but not NESH/Abi-3, is expressed. The expression of NESH/Abi-3 caused degradation of endogenous Abi-1, which led to the formation of a NESH/Abi-3-based WAVE2 complex. When these cells were plated on fibronectin-coated dishes, the translocation of WAVE2 to the plasma membrane was significantly reduced and the formation of peripheral lamellipodial structures was disturbed, suggesting that the NESH/Abi-3-based WAVE2 complex was unable to help produce lamellipodial protrusions. Next, Abi-1, Abi-2, or NESH/Abi-3 was expressed in v-src-transformed NIH3T3 cells. Only in NESH/Abi-3-expressed cells did treatment with an Abl kinase inhibitor, imatinib mesylate, or siRNA-mediated knockdown of c-Abl promote the formation of invadopodia, which are ventral membrane protrusions with extracellular matrix degradation activity. Structural studies showed that a linker region between the proline-rich regions and the Src homology 3 (SH3) domain of Abi-1 is crucial for its interaction with c-Abl and c-Abl-mediated phosphorylation of WAVE2. The NESH/Abi-3-based WAVE2 complex is functionally distinct from the Abi-1-based one, and NESH/Abi-3 may be involved in the formation of ventral protrusions under certain conditions.
Uhl, Juli D.; Cook, Tiffany A.; Gebelein, Brian
2010-01-01
Hox transcription factors specify numerous cell fates along the anterior-posterior axis by regulating the expression of downstream target genes. While expression analysis has uncovered large numbers of de-regulated genes in cells with altered Hox activity, determining which are direct versus indirect targets has remained a significant challenge. Here, we characterize the DNA binding activity of Hox transcription factor complexes on eight experimentally verified cis-regulatory elements. Hox factors regulate the activity of each element by forming protein complexes with two cofactor proteins, Extradenticle (Exd) and Homothorax (Hth). Using comparative DNA binding assays, we found that a number of flexible arrangements of Hox, Exd, and Hth binding sites mediate cooperative transcription factor complexes. Moreover, analysis of a Distal-less regulatory element (DMXR) that is repressed by abdominal Hox factors revealed that suboptimal binding sites can be combined to form high affinity transcription complexes. Lastly, we determined that the anterior Hox factors are more dependent upon Exd and Hth for complex formation than posterior Hox factors. Based upon these findings, we suggest a general set of guidelines to serve as a basis for designing bioinformatics algorithms aimed at identifying Hox regulatory elements using the wealth of recently sequenced genomes. PMID:20398649
New conformal mapping for adaptive resolving of the complex singularities of Stokes wave
Dyachenko, Sergey A.; A. Silantyev, Denis
2017-01-01
A new highly efficient method is developed for computation of travelling periodic waves (Stokes waves) on the free surface of deep water. A convergence of numerical approximation is determined by the complex singularities above the free surface for the analytical continuation of the travelling wave into the complex plane. An auxiliary conformal mapping is introduced which moves singularities away from the free surface thus dramatically speeding up numerical convergence by adapting the numerical grid for resolving singularities while being consistent with the fluid dynamics. The efficiency of that conformal mapping is demonstrated for the Stokes wave approaching the limiting Stokes wave (the wave of the greatest height) which significantly expands the family of numerically accessible solutions. It allows us to provide a detailed study of the oscillatory approach of these solutions to the limiting wave. Generalizations of the conformal mapping to resolve multiple singularities are also introduced. PMID:28690418
New conformal mapping for adaptive resolving of the complex singularities of Stokes wave.
Lushnikov, Pavel M; Dyachenko, Sergey A; A Silantyev, Denis
2017-06-01
A new highly efficient method is developed for computation of travelling periodic waves (Stokes waves) on the free surface of deep water. A convergence of numerical approximation is determined by the complex singularities above the free surface for the analytical continuation of the travelling wave into the complex plane. An auxiliary conformal mapping is introduced which moves singularities away from the free surface thus dramatically speeding up numerical convergence by adapting the numerical grid for resolving singularities while being consistent with the fluid dynamics. The efficiency of that conformal mapping is demonstrated for the Stokes wave approaching the limiting Stokes wave (the wave of the greatest height) which significantly expands the family of numerically accessible solutions. It allows us to provide a detailed study of the oscillatory approach of these solutions to the limiting wave. Generalizations of the conformal mapping to resolve multiple singularities are also introduced.
Scientific and Regulatory Considerations for Generic Complex Drug Products Containing Nanomaterials.
Zheng, Nan; Sun, Dajun D; Zou, Peng; Jiang, Wenlei
2017-05-01
In the past few decades, the development of medicine at the nanoscale has been applied to oral and parenteral dosage forms in a wide range of therapeutic areas to enhance drug delivery and reduce toxicity. An obvious response to these benefits is reflected in higher market shares of complex drug products containing nanomaterials than that of conventional formulations containing the same active ingredient. The surging market interest has encouraged the pharmaceutical industry to develop cost-effective generic versions of complex drug products based on nanotechnology when the associated patent and exclusivity on the reference products have expired. Due to their complex nature, nanotechnology-based drugs present unique challenges in determining equivalence standards between generic and innovator products. This manuscript attempts to provide the scientific rationales and regulatory considerations of key equivalence standards (e.g., in vivo studies and in vitro physicochemical characterization) for oral drugs containing nanomaterials, iron-carbohydrate complexes, liposomes, protein-bound drugs, nanotube-forming drugs, and nano emulsions. It also presents active research studies in bridging regulatory and scientific gaps for establishing equivalence of complex products containing nanomaterials. We hope that open communication among industry, academia, and regulatory agencies will accelerate the development and approval processes of generic complex products based on nanotechnology.
Liu, T Y; Chiu, T L; Clarkson, P A; Chow, K W
2017-09-01
Rogue waves of evolution systems are displacements which are localized in both space and time. The locations of the points of maximum displacements of the wave profiles may correlate with the trajectories of the poles of the exact solutions from the perspective of complex variables through analytic continuation. More precisely, the location of the maximum height of the rogue wave in laboratory coordinates (real space and time) is conjectured to be equal to the real part of the pole of the exact solution, if the spatial coordinate is allowed to be complex. This feature can be verified readily for the Peregrine breather (lowest order rogue wave) of the nonlinear Schrödinger equation. This connection is further demonstrated numerically here for more complicated scenarios, namely the second order rogue wave of the Boussinesq equation (for bidirectional long waves in shallow water), an asymmetric second order rogue wave for the nonlinear Schrödinger equation (as evolution system for slowly varying wave packets), and a symmetric second order rogue wave of coupled Schrödinger systems. Furthermore, the maximum displacements in physical space occur at a time instant where the trajectories of the poles in the complex plane reverse directions. This property is conjectured to hold for many other systems, and will help to determine the maximum amplitudes of rogue waves.
NASA Astrophysics Data System (ADS)
Liu, T. Y.; Chiu, T. L.; Clarkson, P. A.; Chow, K. W.
2017-09-01
Rogue waves of evolution systems are displacements which are localized in both space and time. The locations of the points of maximum displacements of the wave profiles may correlate with the trajectories of the poles of the exact solutions from the perspective of complex variables through analytic continuation. More precisely, the location of the maximum height of the rogue wave in laboratory coordinates (real space and time) is conjectured to be equal to the real part of the pole of the exact solution, if the spatial coordinate is allowed to be complex. This feature can be verified readily for the Peregrine breather (lowest order rogue wave) of the nonlinear Schrödinger equation. This connection is further demonstrated numerically here for more complicated scenarios, namely the second order rogue wave of the Boussinesq equation (for bidirectional long waves in shallow water), an asymmetric second order rogue wave for the nonlinear Schrödinger equation (as evolution system for slowly varying wave packets), and a symmetric second order rogue wave of coupled Schrödinger systems. Furthermore, the maximum displacements in physical space occur at a time instant where the trajectories of the poles in the complex plane reverse directions. This property is conjectured to hold for many other systems, and will help to determine the maximum amplitudes of rogue waves.
Sato, Masanao; Tsuda, Kenichi; Wang, Lin; Coller, John; Watanabe, Yuichiro; Glazebrook, Jane; Katagiri, Fumiaki
2010-01-01
Biological signaling processes may be mediated by complex networks in which network components and network sectors interact with each other in complex ways. Studies of complex networks benefit from approaches in which the roles of individual components are considered in the context of the network. The plant immune signaling network, which controls inducible responses to pathogen attack, is such a complex network. We studied the Arabidopsis immune signaling network upon challenge with a strain of the bacterial pathogen Pseudomonas syringae expressing the effector protein AvrRpt2 (Pto DC3000 AvrRpt2). This bacterial strain feeds multiple inputs into the signaling network, allowing many parts of the network to be activated at once. mRNA profiles for 571 immune response genes of 22 Arabidopsis immunity mutants and wild type were collected 6 hours after inoculation with Pto DC3000 AvrRpt2. The mRNA profiles were analyzed as detailed descriptions of changes in the network state resulting from the genetic perturbations. Regulatory relationships among the genes corresponding to the mutations were inferred by recursively applying a non-linear dimensionality reduction procedure to the mRNA profile data. The resulting static network model accurately predicted 23 of 25 regulatory relationships reported in the literature, suggesting that predictions of novel regulatory relationships are also accurate. The network model revealed two striking features: (i) the components of the network are highly interconnected; and (ii) negative regulatory relationships are common between signaling sectors. Complex regulatory relationships, including a novel negative regulatory relationship between the early microbe-associated molecular pattern-triggered signaling sectors and the salicylic acid sector, were further validated. We propose that prevalent negative regulatory relationships among the signaling sectors make the plant immune signaling network a “sector-switching” network, which effectively balances two apparently conflicting demands, robustness against pathogenic perturbations and moderation of negative impacts of immune responses on plant fitness. PMID:20661428
Lamellipodin and the Scar/WAVE complex cooperate to promote cell migration in vivo
Law, Ah-Lai; Vehlow, Anne; Kotini, Maria; Dodgson, Lauren; Soong, Daniel; Theveneau, Eric; Bodo, Cristian; Taylor, Eleanor; Navarro, Christel; Perera, Upamali; Michael, Magdalene; Dunn, Graham A.; Bennett, Daimark; Mayor, Roberto
2013-01-01
Cell migration is essential for development, but its deregulation causes metastasis. The Scar/WAVE complex is absolutely required for lamellipodia and is a key effector in cell migration, but its regulation in vivo is enigmatic. Lamellipodin (Lpd) controls lamellipodium formation through an unknown mechanism. Here, we report that Lpd directly binds active Rac, which regulates a direct interaction between Lpd and the Scar/WAVE complex via Abi. Consequently, Lpd controls lamellipodium size, cell migration speed, and persistence via Scar/WAVE in vitro. Moreover, Lpd knockout mice display defective pigmentation because fewer migrating neural crest-derived melanoblasts reach their target during development. Consistently, Lpd regulates mesenchymal neural crest cell migration cell autonomously in Xenopus laevis via the Scar/WAVE complex. Further, Lpd’s Drosophila melanogaster orthologue Pico binds Scar, and both regulate collective epithelial border cell migration. Pico also controls directed cell protrusions of border cell clusters in a Scar-dependent manner. Taken together, Lpd is an essential, evolutionary conserved regulator of the Scar/WAVE complex during cell migration in vivo. PMID:24247431
WAVE2 Forms a Complex with PKA and Is Involved in PKA Enhancement of Membrane Protrusions*
Yamashita, Hiroshi; Ueda, Kazumitsu; Kioka, Noriyuki
2011-01-01
PKA contributes to many physiological processes, including glucose homeostasis and cell migration. The substrate specificity of PKA is low compared with other kinases; thus, complex formation with A-kinase-anchoring proteins is important for the localization of PKA in specific subcellular regions and the phosphorylation of specific substrates. Here, we show that PKA forms a complex with WAVE2 (Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2) in MDA-MB-231 breast cancer cells and mouse brain extracts. Two separate regions of WAVE2 are involved in WAVE2-PKA complex formation. This complex localizes to the leading edge of MDA-MB-231 cells. PKA activation results in enlargement of the membrane protrusion. WAVE2 depletion impairs PKA localization at membrane protrusions and the enlargement of membrane protrusion induced by PKA activation. Together, these results suggest that WAVE2 works as an A-kinase-anchoring protein that recruits PKA at membrane protrusions and plays a role in the enlargement of membrane protrusions induced by PKA activation. PMID:21119216
Zago, Giulia; Biondini, Marco; Camonis, Jacques; Parrini, Maria Carla
2017-05-12
Cell migration is central to many developmental, physiologic and pathological processes, including cancer progression. The Ral GTPases (RalA and RalB) which act down-stream the Ras oncogenes, are key players in the coordination between membrane trafficking and actin polymerization. A major direct effector of Ral, the exocyst complex, works in polarized exocytosis and is at the center of multiple protein-protein interactions that support cell migration by promoting protrusion formation, front-rear polarization, and extra-cellular matrix degradation. In this review we describe the recent advancements in deciphering the molecular mechanisms underlying this role of Ral via exocyst on cell migration. Among others, we will discuss the recently identified cross-talk between Ral and Rac1 pathways: exocyst binds to a negative regulator (the RacGAP SH3BP1) and to the major effector (the Wave Regulatory Complex, WRC) of Rac1, the master regulator of protrusions. Next challenge will be to better characterize the dynamics in space and in time of these molecular interplays, to better understand the pleiotropic functions of Ral in both normal and cancer cells.
Federal Register 2010, 2011, 2012, 2013, 2014
2013-03-27
... from interested persons. \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization... simple, non-complex orders only. The Exchange now proposes to establish the Complex Order Router Subsidy... simple, non-complex orders under the ORS Program. The Participants would have to agree that they are not...
Lloyd, Julie C.; Raines, Christine A.
2011-01-01
In darkened leaves the Calvin cycle enzymes glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and phosphoribulokinase (PRK) form a regulatory multi-enzyme complex with the small chloroplast protein CP12. GAPDH also forms a high molecular weight regulatory mono-enzyme complex. Given that there are different reports as to the number and subunit composition of these complexes and that enzyme regulatory mechanisms are known to vary between species, it was reasoned that protein–protein interactions may also vary between species. Here, this variation is investigated. This study shows that two different tetramers of GAPDH (an A2B2 heterotetramer and an A4 homotetramer) have the capacity to form part of the PRK/GAPDH/CP12 complex. The role of the PRK/GAPDH/CP12 complex is not simply to regulate the ‘non-regulatory’ A4 GAPDH tetramer. This study also demonstrates that the abundance and nature of PRK/GAPDH/CP12 interactions are not equal in all species and that whilst NAD enhances complex formation in some species, this is not sufficient for complex formation in others. Furthermore, it is shown that the GAPDH mono-enzyme complex is more abundant as a 2(A2B2) complex, rather than the larger 4(A2B2) complex. This smaller complex is sensitive to cellular metabolites indicating that it is an important regulatory isoform of GAPDH. This comparative study has highlighted considerable heterogeneity in PRK and GAPDH protein interactions between closely related species and the possible underlying physiological basis for this is discussed. PMID:21498632
Miles, J
1980-04-01
Transversely periodic solitary-wave solutions of the Boussinesq equations (which govern wave propagation in a weakly dispersive, weakly nonlinear physical system) are determined. The solutions for negative dispersion (e.g., gravity waves) are singular and therefore physically unacceptable. The solutions for positive dispersion (e.g., capillary waves or magnetosonic waves in a plasma) are physically acceptable except in a limited parametric interval, in which they are complex. The two end points of this interval are associated with (two different) resonant interactions among three basic solitary waves, two of which are two-dimensional complex conjugates and the third of which is one-dimensional and real.
Focusing Leaky Waves: A Class of Electromagnetic Localized Waves with Complex Spectra
NASA Astrophysics Data System (ADS)
Fuscaldo, Walter; Comite, Davide; Boesso, Alessandro; Baccarelli, Paolo; Burghignoli, Paolo; Galli, Alessandro
2018-05-01
Localized waves, i.e., the wide class of limited-diffraction, limited-dispersion solutions to the wave equation are generally characterized by real wave numbers. We consider the role played by localized waves with generally complex "leaky" wave numbers. First, the impact of the imaginary part of the wave number (i.e., the leakage constant) on the diffractive (spatial broadening) features of monochromatic localized solutions (i.e., beams) is rigorously evaluated. Then general conditions are derived to show that only a restricted class of spectra (either real or complex) allows for generating a causal localized wave. It turns out that backward leaky waves fall into this category. On this ground, several criteria for the systematic design of wideband radiators, namely, periodic radial waveguides based on backward leaky waves, are established in the framework of leaky-wave theory. An effective design method is proposed to minimize the frequency dispersion of the proposed class of devices and the impact of the "leakage" on the dispersive (temporal broadening) features of polychromatic localized solutions (i.e., pulses) is accounted for. Numerical results corroborate the concept, clearly highlighting the advantages and limitations of the leaky-wave approach for the generation of localized pulses at millimeter-wave frequencies, where energy focusing is in high demand in modern applications.
Regulatory activities of transposable elements: from conflicts to benefits
Chuong, Edward B.; Elde, Nels C.; Feschotte, Cédric
2017-01-01
Transposable elements (TEs) are a prolific source of tightly regulated, biochemically active non-coding elements, such as transcription factor binding sites and non-coding RNAs. A wealth of recent studies reinvigorates the idea that these elements are pervasively co-opted for the regulation of host genes. We argue that the inherent genetic properties of TEs and conflicting relationships with their hosts facilitate their recruitment for regulatory functions in diverse genomes. We review recent findings supporting the long-standing hypothesis that the waves of TE invasions endured by organisms for eons have catalyzed the evolution of gene regulatory networks. We also discuss the challenges of dissecting and interpreting the phenotypic impact of regulatory activities encoded by TEs in health and disease. PMID:27867194
Bryce, Nicole S; Reynolds, Albert B; Koleske, Anthony J; Weaver, Alissa M
2013-01-01
Epithelial morphogenesis is a dynamic process that involves coordination of signaling and actin cytoskeletal rearrangements. We analyzed the contribution of the branched actin regulator WAVE2 in the development of 3-dimensional (3D) epithelial structures. WAVE2-knockdown (WAVE2-KD) cells formed large multi-lobular acini that continued to proliferate at an abnormally late stage compared to control acini. Immunostaining of the cell-cell junctions of WAVE2-KD acini revealed weak and heterogeneous E-cadherin staining despite little change in actin filament localization to the same junctions. Analysis of cadherin expression demonstrated a decrease in E-cadherin and an increase in N-cadherin protein and mRNA abundance in total cell lysates. In addition, WAVE2-KD cells exhibited an increase in the mRNA levels of the epithelial-mesenchymal transition (EMT)-associated transcription factor Twist1. KD of Twist1 expression in WAVE2-KD cells reversed the cadherin switching and completely rescued the aberrant 3D morphological phenotype. Activity of the WAVE2 complex binding partner Abl kinase was also increased in WAVE2-KD cells, as assessed by tyrosine phosphorylation of the Abl substrate CrkL. Inhibition of Abl with STI571 rescued the multi-lobular WAVE2-KD 3D phenotype whereas overexpression of Abl kinase phenocopied the WAVE2-KD phenotype. The WAVE2 complex regulates breast epithelial morphology by a complex mechanism involving repression of Twist1 expression and Abl kinase activity. These data reveal a critical role for WAVE2 complex in regulation of cellular signaling and epithelial morphogenesis.
A novel role for WAVE1 in controlling actin network growth rate and architecture.
Sweeney, Meredith O; Collins, Agnieszka; Padrick, Shae B; Goode, Bruce L
2015-02-01
Branched actin filament networks in cells are assembled through the combined activities of Arp2/3 complex and different WASP/WAVE proteins. Here we used TIRF and electron microscopy to directly compare for the first time the assembly kinetics and architectures of actin filament networks produced by Arp2/3 complex and dimerized VCA regions of WAVE1, WAVE2, or N-WASP. WAVE1 produced strikingly different networks from WAVE2 or N-WASP, which comprised unexpectedly short filaments. Further analysis showed that the WAVE1-specific activity stemmed from an inhibitory effect on filament elongation both in the presence and absence of Arp2/3 complex, which was observed even at low stoichiometries of WAVE1 to actin monomers, precluding an effect from monomer sequestration. Using a series of VCA chimeras, we mapped the elongation inhibitory effects of WAVE1 to its WH2 ("V") domain. Further, mutating a single conserved lysine residue potently disrupted WAVE1's inhibitory effects. Taken together, our results show that WAVE1 has unique activities independent of Arp2/3 complex that can govern both the growth rates and architectures of actin filament networks. Such activities may underlie previously observed differences between the cellular functions of WAVE1 and WAVE2. © 2015 Sweeney 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).
Equivalence of complex drug products: advances in and challenges for current regulatory frameworks.
Hussaarts, Leonie; Mühlebach, Stefan; Shah, Vinod P; McNeil, Scott; Borchard, Gerrit; Flühmann, Beat; Weinstein, Vera; Neervannan, Sesha; Griffiths, Elwyn; Jiang, Wenlei; Wolff-Holz, Elena; Crommelin, Daan J A; de Vlieger, Jon S B
2017-11-01
Biotechnology and nanotechnology provide a growing number of innovator-driven complex drug products and their copy versions. Biologics exemplify one category of complex drugs, but there are also nonbiological complex drug products, including many nanomedicines, such as iron-carbohydrate complexes, drug-carrying liposomes or emulsions, and glatiramoids. In this white paper, which stems from a 1-day conference at the New York Academy of Sciences, we discuss regulatory frameworks in use worldwide (e.g., the U.S. Food and Drug Administration, the European Medicines Agency, the World Health Organization) to approve these complex drug products and their follow-on versions. One of the key questions remains how to assess equivalence of these complex products. We identify a number of points for which consensus was found among the stakeholders who were present: scientists from innovator and generic/follow-on companies, academia, and regulatory bodies from different parts of the world. A number of topics requiring follow-up were identified: (1) assessment of critical attributes to establish equivalence for follow-on versions, (2) the need to publish scientific findings in the public domain to further progress in the field, (3) the necessity to develop worldwide consensus regarding nomenclature and labeling of these complex products, and (4) regulatory actions when substandard complex drug products are identified. © 2017 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals, Inc. on behalf of New York Academy of Sciences.
Density waves at the interface of a binary complex plasma
NASA Astrophysics Data System (ADS)
Yang, Li; Schwabe, Mierk; Zhdanov, Sergey; Thomas, Hubertus M.; Lipaev, Andrey M.; Molotkov, Vladimir I.; Fortov, Vladimir E.; Zhang, Jing; Du, Cheng-Ran
2017-01-01
Density waves were studied in a phase-separated binary complex plasma under microgravity conditions. For the big particles, waves were self-excited by the two-stream instability, while for small particles, they were excited by heartbeat instability with the presence of reversed propagating pulses of a different frequency. By studying the dynamics of wave crests at the interface, we recognize a “collision zone” and a “merger zone” before and after the interface, respectively. The results provide a generic picture of wave-wave interaction at the interface between two “mediums”.
Self-consistent adjoint analysis for topology optimization of electromagnetic waves
NASA Astrophysics Data System (ADS)
Deng, Yongbo; Korvink, Jan G.
2018-05-01
In topology optimization of electromagnetic waves, the Gâteaux differentiability of the conjugate operator to the complex field variable results in the complexity of the adjoint sensitivity, which evolves the original real-valued design variable to be complex during the iterative solution procedure. Therefore, the self-inconsistency of the adjoint sensitivity is presented. To enforce the self-consistency, the real part operator has been used to extract the real part of the sensitivity to keep the real-value property of the design variable. However, this enforced self-consistency can cause the problem that the derived structural topology has unreasonable dependence on the phase of the incident wave. To solve this problem, this article focuses on the self-consistent adjoint analysis of the topology optimization problems for electromagnetic waves. This self-consistent adjoint analysis is implemented by splitting the complex variables of the wave equations into the corresponding real parts and imaginary parts, sequentially substituting the split complex variables into the wave equations with deriving the coupled equations equivalent to the original wave equations, where the infinite free space is truncated by the perfectly matched layers. Then, the topology optimization problems of electromagnetic waves are transformed into the forms defined on real functional spaces instead of complex functional spaces; the adjoint analysis of the topology optimization problems is implemented on real functional spaces with removing the variational of the conjugate operator; the self-consistent adjoint sensitivity is derived, and the phase-dependence problem is avoided for the derived structural topology. Several numerical examples are implemented to demonstrate the robustness of the derived self-consistent adjoint analysis.
Federal Register 2010, 2011, 2012, 2013, 2014
2013-09-23
... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-70425; File No. SR-NYSEArca-2013-90] Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule... Complex Orders and Complex Order Auction Eligible Orders in Accordance With the Guaranteed Participation...
Dispersion features of complex waves in a graphene-coated semiconductor nanowire
NASA Astrophysics Data System (ADS)
Yu, Pengchao; Fesenko, Volodymyr I.; Tuz, Vladimir R.
2018-05-01
The dispersion features of a graphene-coated semiconductor nanowire operating in the terahertz frequency band are consistently studied in the framework of a special theory of complex waves. Detailed classification of the waveguide modes was carried out based on the analysis of characteristics of the phase and attenuation constants obtained from the complex roots of characteristic equation. With such a treatment, the waves are attributed to the group of either "proper" or "improper" waves, wherein their type is determined as the trapped surface waves, fast and slow leaky waves, and surface plasmons. The dispersion curves of axially symmetric TM0n and TE0n modes, as well as nonsymmetric hybrid EH1n and HE1n modes, were plotted and analyzed in detail, and both radiative regime of leaky waves and guided regime of trapped surface waves are identified. The peculiarities of propagation of the TM modes of surface plasmons were revealed. Two subregions of existence of surface plasmons were found out where they appear as propagating and reactive waves. The cutoff conditions for higher-order TM modes of surface plasmons were correctly determined.
Fourier Analysis and the Rhythm of Conversation.
ERIC Educational Resources Information Center
Dabbs, James M., Jr.
Fourier analysis, a common technique in engineering, breaks down a complex wave form into its simple sine wave components. Communication researchers have recently suggested that this technique may provide an index of the rhythm of conversation, since vocalizing and pausing produce a complex wave form pattern of alternation between two speakers. To…
Bryce, Nicole S.; Reynolds, Albert B.; Koleske, Anthony J.; Weaver, Alissa M.
2013-01-01
Background Epithelial morphogenesis is a dynamic process that involves coordination of signaling and actin cytoskeletal rearrangements. Principal Findings We analyzed the contribution of the branched actin regulator WAVE2 in the development of 3-dimensional (3D) epithelial structures. WAVE2-knockdown (WAVE2-KD) cells formed large multi-lobular acini that continued to proliferate at an abnormally late stage compared to control acini. Immunostaining of the cell-cell junctions of WAVE2-KD acini revealed weak and heterogeneous E-cadherin staining despite little change in actin filament localization to the same junctions. Analysis of cadherin expression demonstrated a decrease in E-cadherin and an increase in N-cadherin protein and mRNA abundance in total cell lysates. In addition, WAVE2-KD cells exhibited an increase in the mRNA levels of the epithelial-mesenchymal transition (EMT)-associated transcription factor Twist1. KD of Twist1 expression in WAVE2-KD cells reversed the cadherin switching and completely rescued the aberrant 3D morphological phenotype. Activity of the WAVE2 complex binding partner Abl kinase was also increased in WAVE2-KD cells, as assessed by tyrosine phosphorylation of the Abl substrate CrkL. Inhibition of Abl with STI571 rescued the multi-lobular WAVE2-KD 3D phenotype whereas overexpression of Abl kinase phenocopied the WAVE2-KD phenotype. Conclusions The WAVE2 complex regulates breast epithelial morphology by a complex mechanism involving repression of Twist1 expression and Abl kinase activity. These data reveal a critical role for WAVE2 complex in regulation of cellular signaling and epithelial morphogenesis. PMID:23691243
Moored offshore structures - evaluation of forces in elastic mooring lines
NASA Astrophysics Data System (ADS)
Crudu, L.; Obreja, D. C.; Marcu, O.
2016-08-01
In most situations, the high frequency motions of the floating structure induce important effects in the mooring lines which affect also the motions of the structure. The experience accumulated during systematic experimental tests and calculations, carried out for different moored floating structures, showed a complex influence of various parameters on the dynamic effects. Therefore, it was considered that a systematic investigation is necessary. Due to the complexity of hydrodynamics aspects of offshore structures behaviour, experimental tests are practically compulsory in order to be able to properly evaluate and then to validate their behaviour in real sea. Moreover the necessity to carry out hydrodynamic tests is often required by customers, classification societies and other regulatory bodies. Consequently, the correct simulation of physical properties of the complex scaled models becomes a very important issue. The paper is investigating such kind of problems identifying the possible simplification, generating different approaches. One of the bases of the evaluation has been found consideringtheresults of systematic experimental tests on the dynamic behaviour of a mooring chain reproduced at five different scales. Dynamic effects as well as the influences of the elasticity simulation for 5 different scales are evaluated together. The paper presents systematic diagrams and practical results for a typical moored floating structure operating as pipe layer based on motion evaluations and accelerations in waves.
Declercq, Nico F; Leroy, Oswald
2011-08-01
Plane waves are solutions of the visco-elastic wave equation. Their wave vector can be real for homogeneous plane waves or complex for inhomogeneous and evanescent plane waves. Although interesting from a theoretical point of view, complex wave vectors normally only emerge naturally when propagation or scattering is studied of sound under the appearance of damping effects. Because of the particular behavior of inhomogeneous and evanescent waves and their estimated efficiency for surface wave generation, bounded beams, experimentally mimicking their infinite counterparts similar to (wide) Gaussian beams imitating infinite harmonic plane waves, are of special interest in this report. The study describes the behavior of bounded inhomogeneous and bounded evanescent waves in terms of amplitude and phase distribution as well as energy flow direction. The outcome is of importance to the applicability of bounded inhomogeneous ultrasonic waves for nondestructive testing. Copyright © 2011. Published by Elsevier B.V.
Measuring and Modeling the U.S. Regulatory Ecosystem
NASA Astrophysics Data System (ADS)
Bommarito, Michael J., II; Katz, Daniel Martin
2017-09-01
Over the last 23 years, the U.S. Securities and Exchange Commission has required over 34,000 companies to file over 165,000 annual reports. These reports, the so-called "Form 10-Ks," contain a characterization of a company's financial performance and its risks, including the regulatory environment in which a company operates. In this paper, we analyze over 4.5 million references to U.S. Federal Acts and Agencies contained within these reports to measure the regulatory ecosystem, in which companies are organisms inhabiting a regulatory environment. While individuals across the political, economic, and academic world frequently refer to trends in this regulatory ecosystem, far less attention has been paid to supporting such claims with large-scale, longitudinal data. In this paper, in addition to positing a model of regulatory ecosystems, we document an increase in the regulatory energy per filing, i.e., a warming "temperature." We also find that the diversity of the regulatory ecosystem has been increasing over the past two decades. These findings support the claim that regulatory activity and complexity are increasing, and this framework contributes an important step towards improving academic and policy discussions around legal complexity and regulation.
WAVE2 is regulated by multiple phosphorylation events within its VCA domain
Pocha, Shirin M; Cory, Giles O
2009-01-01
The (Wiskott-Aldrich Syndrome Protein)-family verprolin homologous protein (WAVE) family of proteins occupies a pivotal position in the cell, converting extracellular signals into the formation of branched filamentous (F) actin structures. WAVE proteins contain a verprolin central acidic (VCA) domain at their C-terminus, responsible for binding to and activating the Arp2/3 complex, which in-turn nucleates the formation of new actin filaments. Here we identify five Casein Kinase 2 (CK2) phosphorylation sites within the VCA domain of WAVE2, serines 482, 484, 488, 489, and 497. Phosphorylation of these sites is required for a high affinity interaction with the Arp2/3 complex. Phosphorylation of ser 482 and 484 specifically inhibits the activation of the Arp2/3 complex by the WAVE2 VCA domain, but has no effect on the affinity for the Arp2/3 complex when the other phosphorylation sites are occupied. We demonstrate phosphorylation of all five sites on endogenous WAVE2 and show that their mutation to non-phosphorylatable alanine residues inhibits WAVE2 function in vivo, inhibiting cell ruffling and disrupting the integrity of the leading edge of migrating cells. Cell Motil. Cytoskeleton 2008. © 2008 Wiley-Liss, Inc. PMID:19012317
WAVE2 is regulated by multiple phosphorylation events within its VCA domain.
Pocha, Shirin M; Cory, Giles O
2009-01-01
The (Wiskott-Aldrich Syndrome Protein)-family verprolin homologous protein (WAVE) family of proteins occupies a pivotal position in the cell, converting extracellular signals into the formation of branched filamentous (F) actin structures. WAVE proteins contain a verprolin central acidic (VCA) domain at their C-terminus, responsible for binding to and activating the Arp2/3 complex, which in-turn nucleates the formation of new actin filaments. Here we identify five Casein Kinase 2 (CK2) phosphorylation sites within the VCA domain of WAVE2, serines 482, 484, 488, 489, and 497. Phosphorylation of these sites is required for a high affinity interaction with the Arp2/3 complex. Phosphorylation of ser 482 and 484 specifically inhibits the activation of the Arp2/3 complex by the WAVE2 VCA domain, but has no effect on the affinity for the Arp2/3 complex when the other phosphorylation sites are occupied. We demonstrate phosphorylation of all five sites on endogenous WAVE2 and show that their mutation to non-phosphorylatable alanine residues inhibits WAVE2 function in vivo, inhibiting cell ruffling and disrupting the integrity of the leading edge of migrating cells. (c) 2008 Wiley-Liss, Inc.
Federal Register 2010, 2011, 2012, 2013, 2014
2013-11-07
... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-70797; File No. SR-BOX-2013-43] Self-Regulatory... Proposed Rule Change To Permit Complex Orders To Participate in Price Improvement Periods November 1, 2013... to permit Complex Orders to participate in Price Improvement Periods (the ``COPIP'') and to make...
NASA Astrophysics Data System (ADS)
Huang, Xingguo; Sun, Hui
2018-05-01
Gaussian beam is an important complex geometrical optical technology for modeling seismic wave propagation and diffraction in the subsurface with complex geological structure. Current methods for Gaussian beam modeling rely on the dynamic ray tracing and the evanescent wave tracking. However, the dynamic ray tracing method is based on the paraxial ray approximation and the evanescent wave tracking method cannot describe strongly evanescent fields. This leads to inaccuracy of the computed wave fields in the region with a strong inhomogeneous medium. To address this problem, we compute Gaussian beam wave fields using the complex phase by directly solving the complex eikonal equation. In this method, the fast marching method, which is widely used for phase calculation, is combined with Gauss-Newton optimization algorithm to obtain the complex phase at the regular grid points. The main theoretical challenge in combination of this method with Gaussian beam modeling is to address the irregular boundary near the curved central ray. To cope with this challenge, we present the non-uniform finite difference operator and a modified fast marching method. The numerical results confirm the proposed approach.
Complexity-action duality of the shock wave geometry in a massive gravity theory
NASA Astrophysics Data System (ADS)
Miao, Yan-Gang; Zhao, Long
2018-01-01
On the holographic complexity dual to the bulk action, we investigate the action growth for a shock wave geometry in a massive gravity theory within the Wheeler-DeWitt (WDW) patch at the late time limit. For a global shock wave, the graviton mass does not affect the action growth in the bulk, i.e., the complexity on the boundary, showing that the action growth (complexity) is the same for both the Einstein gravity and the massive gravity. Nevertheless, for a local shock wave that depends on transverse coordinates, the action growth (complexity) caused by the boundary disturbance (perturbation) is proportional to the butterfly velocity for the two gravity theories, but the butterfly velocity of the massive gravity theory is smaller than that of the Einstein gravity theory, indicating that the action growth (complexity) of the massive gravity is depressed by the graviton mass. In addition, we extend the black hole thermodynamics of the massive gravity and obtain the right Smarr formula.
Waves associated to COMPLEX EVENTS observed by STEREO
NASA Astrophysics Data System (ADS)
Siu Tapia, A. L.; Blanco-Cano, X.; Kajdic, P.; Aguilar-Rodriguez, E.; Russell, C. T.; Jian, L. K.; Luhmann, J. G.
2012-12-01
Complex Events are formed by two or more large-scale solar wind structures which interact in space. Typical cases are interactions of: (i) a Magnetic Cloud/Interplanetary Coronal Mass Ejection (MC/ICME) with another MC/ICME transient; and (ii) an ICME followed by a Stream Interaction Region (SIR). Complex Events are of importance for space weather studies and studying them can enhance our understanding of collisionless plasma physics. Some of these structures can produce or enhance southward magnetic fields, a key factor in geomagnetic storm generation. Using data from the STEREO mission during the years 2006-2011, we found 17 Complex Events preceded by a shock wave. We use magnetic field and plasma data to study the micro-scale structure of the shocks, and the waves associated to these shocks and within Complex Events structures. To determine wave characteristics we perform Power Spectra and Minimum Variance Analysis. We also use PLASTIC WAP protons data to study foreshock extensions and the relationship between Complex Regions and particle acceleration to suprathermal energies.
Observation of frequency cutoff for self-excited dust acoustic waves
NASA Astrophysics Data System (ADS)
Nosenko, V.; Zhdanov, S. K.; Morfill, G. E.; Kim, S.-H.; Heinrich, J.; Merlino, R. L.
2009-11-01
Complex (dusty) plasmas consist of fine solid particles suspended in a weakly ionized gas. Complex plasmas are excellent model systems to study wave phenomena down to the level of individual ``atoms''. Spontaneously excited dust acoustic waves were observed with high temporal resolution in a suspension of micron-size kaolin particles in a dc discharge in argon. Wave activity was found at frequencies as high as 400 Hz. At high wave numbers, the wave dispersion relation was acoustic-like (frequency proportional to wave number). At low wave numbers, the wave frequency did not tend to zero, but reached a cutoff frequency fc instead. The value of fc declined with distance from the anode. We propose a simple model that explains the observed cutoff by particle confinement in plasma. The existence of a cutoff frequency is very important for the propagation of waves: the waves excited above fc are propagating, and those below fc are evanescent.
ULTRASONIC STUDIES OF THE FUNDAMENTAL MECHANISMS OF RECRYSTALLIZATION AND SINTERING OF METALS
DOE Office of Scientific and Technical Information (OSTI.GOV)
TURNER, JOSEPH A.
2005-11-30
The purpose of this project was to develop a fundamental understanding of the interaction of an ultrasonic wave with complex media, with specific emphases on recrystallization and sintering of metals. A combined analytical, numerical, and experimental research program was implemented. Theoretical models of elastic wave propagation through these complex materials were developed using stochastic wave field techniques. The numerical simulations focused on finite element wave propagation solutions through complex media. The experimental efforts were focused on corroboration of the models developed and on the development of new experimental techniques. The analytical and numerical research allows the experimental results to bemore » interpreted quantitatively.« less
Wave field synthesis of moving virtual sound sources with complex radiation properties.
Ahrens, Jens; Spors, Sascha
2011-11-01
An approach to the synthesis of moving virtual sound sources with complex radiation properties in wave field synthesis is presented. The approach exploits the fact that any stationary sound source of finite spatial extent radiates spherical waves at sufficient distance. The angular dependency of the radiation properties of the source under consideration is reflected by the amplitude and phase distribution on the spherical wave fronts. The sound field emitted by a uniformly moving monopole source is derived and the far-field radiation properties of the complex virtual source under consideration are incorporated in order to derive a closed-form expression for the loudspeaker driving signal. The results are illustrated via numerical simulations of the synthesis of the sound field of a sample moving complex virtual source.
Soundararajan, Rama; Ziera, Tim; Koo, Eric; Ling, Karen; Wang, Jian; Borden, Steffen A.; Pearce, David
2012-01-01
Hormone regulation of ion transport in the kidney tubules is essential for fluid and electrolyte homeostasis in vertebrates. A large body of evidence has suggested that transporters and channels exist in multiprotein regulatory complexes; however, relatively little is known about the composition of these complexes or their assembly. The epithelial sodium channel (ENaC) in particular is tightly regulated by the salt-regulatory hormone aldosterone, which acts at least in part by increasing expression of the serine-threonine kinase SGK1. Here we show that aldosterone induces the formation of a 1.0–1.2-MDa plasma membrane complex, which includes ENaC, SGK1, and the ENaC inhibitor Nedd4-2, a key target of SGK1. We further show that this complex contains the PDZ domain-containing protein connector enhancer of kinase suppressor of Ras isoform 3 (CNK3). CNK3 physically interacts with ENaC, Nedd4-2, and SGK1; enhances the interactions among them; and stimulates ENaC function in a PDZ domain-dependent, aldosterone-induced manner. These results strongly suggest that CNK3 is a molecular scaffold, which coordinates the assembly of a multiprotein ENaC-regulatory complex and hence plays a central role in Na+ homeostasis. PMID:22851176
Deconstructing the core dynamics from a complex time-lagged regulatory biological circuit.
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].
NASA Technical Reports Server (NTRS)
Craidon, C. B.
1983-01-01
A computer program was developed to extend the geometry input capabilities of previous versions of a supersonic zero lift wave drag computer program. The arbitrary geometry input description is flexible enough to describe almost any complex aircraft concept, so that highly accurate wave drag analysis can now be performed because complex geometries can be represented accurately and do not have to be modified to meet the requirements of a restricted input format.
ERIC Educational Resources Information Center
Muis, Krista R.; Psaradellis, Cynthia; Chevrier, Marianne; Di Leo, Ivana; Lajoie, Susanne P.
2016-01-01
We developed an intervention based on the learning by teaching paradigm to foster self-regulatory processes and better learning outcomes during complex mathematics problem solving in a technology-rich learning environment. Seventy-eight elementary students were randomly assigned to 1 of 2 conditions: learning by preparing to teach, or learning for…
NASA Astrophysics Data System (ADS)
Ganiev, R. F.; Reviznikov, D. L.; Rogoza, A. N.; Slastushenskiy, Yu. V.; Ukrainskiy, L. E.
2017-03-01
A description of a complex approach to investigation of nonlinear wave processes in the human cardiovascular system based on a combination of high-precision methods of measuring a pulse wave, mathematical methods of processing the empirical data, and methods of direct numerical modeling of hemodynamic processes in an arterial tree is given.
Decoding the role of regulatory element polymorphisms in complex disease.
Vockley, Christopher M; Barrera, Alejandro; Reddy, Timothy E
2017-04-01
Genetic variation in gene regulatory elements contributes to diverse human diseases, ranging from rare and severe developmental defects to common and complex diseases such as obesity and diabetes. Early examples of regulatory mechanisms of human diseases involve large chromosomal rearrangements that change the regulatory connections within the genome. Single nucleotide variants in regulatory elements can also contribute to disease, potentially via demonstrated associations with changes in transcription factor binding, enhancer activity, post-translational histone modifications, long-range enhancer-promoter interactions, or RNA polymerase recruitment. Establishing causality between non-coding genetic variants, gene regulation, and disease has recently become more feasible with advances in genome-editing and epigenome-editing technologies. As establishing causal regulatory mechanisms of diseases becomes routine, functional annotation of target genes is likely to emerge as a major bottleneck for translation into patient benefits. In this review, we discuss the history and recent advances in understanding the regulatory mechanisms of human disease, and new challenges likely to be encountered once establishing those mechanisms becomes rote. Copyright © 2016 Elsevier Ltd. All rights reserved.
Garcia de Lomana, Adrian Lopez; Schäuble, Sascha; Valenzuela, Jacob; ...
2015-12-02
Algae accumulate lipids to endure different kinds of environmental stresses including macronutrient starvation. Although this response has been extensively studied, an in depth understanding of the transcriptional regulatory network (TRN) that controls the transition into lipid accumulation remains elusive. In this study, we used a systems biology approach to elucidate the transcriptional program that coordinates the nitrogen starvation-induced metabolic readjustments that drive lipid accumulation in Chlamydomonas reinhardtii. We demonstrate that nitrogen starvation triggered differential regulation of 2147 transcripts, which were co-regulated in 215 distinct modules and temporally ordered as 31 transcriptional waves. An early-stage response was triggered within 12 minmore » that initiated growth arrest through activation of key signaling pathways, while simultaneously preparing the intracellular environment for later stages by modulating transport processes and ubiquitin-mediated protein degradation. Subsequently, central metabolism and carbon fixation were remodeled to trigger the accumulation of triacylglycerols. Further analysis revealed that these waves of genome-wide transcriptional events were coordinated by a regulatory program orchestrated by at least 17 transcriptional regulators, many of which had not been previously implicated in this process. We demonstrate that the TRN coordinates transcriptional downregulation of 57 metabolic enzymes across a period of nearly 4 h to drive an increase in lipid content per unit biomass. Notably, this TRN appears to also drive lipid accumulation during sulfur starvation, while phosphorus starvation induces a different regulatory program. The TRN model described here is available as a community-wide web-resource at http://networks.systemsbiology.net/chlamy-portal. In conclusion, in this work, we have uncovered a comprehensive mechanistic model of the TRN controlling the transition from N starvation to lipid accumulation. The program coordinates sequentially ordered transcriptional waves that simultaneously arrest growth and lead to lipid accumulation. Lastly, this study has generated predictive tools that will aid in devising strategies for the rational manipulation of regulatory and metabolic networks for better biofuel and biomass production.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Garcia de Lomana, Adrian Lopez; Schäuble, Sascha; Valenzuela, Jacob
Algae accumulate lipids to endure different kinds of environmental stresses including macronutrient starvation. Although this response has been extensively studied, an in depth understanding of the transcriptional regulatory network (TRN) that controls the transition into lipid accumulation remains elusive. In this study, we used a systems biology approach to elucidate the transcriptional program that coordinates the nitrogen starvation-induced metabolic readjustments that drive lipid accumulation in Chlamydomonas reinhardtii. We demonstrate that nitrogen starvation triggered differential regulation of 2147 transcripts, which were co-regulated in 215 distinct modules and temporally ordered as 31 transcriptional waves. An early-stage response was triggered within 12 minmore » that initiated growth arrest through activation of key signaling pathways, while simultaneously preparing the intracellular environment for later stages by modulating transport processes and ubiquitin-mediated protein degradation. Subsequently, central metabolism and carbon fixation were remodeled to trigger the accumulation of triacylglycerols. Further analysis revealed that these waves of genome-wide transcriptional events were coordinated by a regulatory program orchestrated by at least 17 transcriptional regulators, many of which had not been previously implicated in this process. We demonstrate that the TRN coordinates transcriptional downregulation of 57 metabolic enzymes across a period of nearly 4 h to drive an increase in lipid content per unit biomass. Notably, this TRN appears to also drive lipid accumulation during sulfur starvation, while phosphorus starvation induces a different regulatory program. The TRN model described here is available as a community-wide web-resource at http://networks.systemsbiology.net/chlamy-portal. In conclusion, in this work, we have uncovered a comprehensive mechanistic model of the TRN controlling the transition from N starvation to lipid accumulation. The program coordinates sequentially ordered transcriptional waves that simultaneously arrest growth and lead to lipid accumulation. Lastly, this study has generated predictive tools that will aid in devising strategies for the rational manipulation of regulatory and metabolic networks for better biofuel and biomass production.« less
Complex systems dynamics in aging: new evidence, continuing questions.
Cohen, Alan A
2016-02-01
There have long been suggestions that aging is tightly linked to the complex dynamics of the physiological systems that maintain homeostasis, and in particular to dysregulation of regulatory networks of molecules. This review synthesizes recent work that is starting to provide evidence for the importance of such complex systems dynamics in aging. There is now clear evidence that physiological dysregulation--the gradual breakdown in the capacity of complex regulatory networks to maintain homeostasis--is an emergent property of these regulatory networks, and that it plays an important role in aging. It can be measured simply using small numbers of biomarkers. Additionally, there are indications of the importance during aging of emergent physiological processes, functional processes that cannot be easily understood through clear metabolic pathways, but can nonetheless be precisely quantified and studied. The overall role of such complex systems dynamics in aging remains an important open question, and to understand it future studies will need to distinguish and integrate related aspects of aging research, including multi-factorial theories of aging, systems biology, bioinformatics, network approaches, robustness, and loss of complexity.
Fecko, Christopher J; Munson, Katherine M; Saunders, Abbie; Sun, Guangxing; Begley, Tadhg P; Lis, John T; Webb, Watt W
2007-01-01
Crosslinking proteins to the nucleic acids they bind affords stable access to otherwise transient regulatory interactions. Photochemical crosslinking provides an attractive alternative to formaldehyde-based protocols, but irradiation with conventional UV sources typically yields inadequate product amounts. Crosslinking with pulsed UV lasers has been heralded as a revolutionary technique to increase photochemical yield, but this method had only been tested on a few protein-nucleic acid complexes. To test the generality of the yield enhancement, we have investigated the benefits of using approximately 150 fs UV pulses to crosslink TATA-binding protein, glucocorticoid receptor and heat shock factor to oligonucleotides in vitro. For these proteins, we find that the quantum yields (and saturating yields) for forming crosslinks using the high-peak intensity femtosecond laser do not improve on those obtained with low-intensity continuous wave (CW) UV sources. The photodamage to the oligonucleotides and proteins also has comparable quantum yields. Measurements of the photochemical reaction yields of several small molecules selected to model the crosslinking reactions also exhibit nearly linear dependences on UV intensity instead of the previously predicted quadratic dependence. Unfortunately, these results disprove earlier assertions that femtosecond pulsed laser sources provide significant advantages over CW radiation for protein-nucleic acid crosslinking.
Egri-Nagy, Attila; Nehaniv, Chrystopher L
2008-01-01
Beyond complexity measures, sometimes it is worthwhile in addition to investigate how complexity changes structurally, especially in artificial systems where we have complete knowledge about the evolutionary process. Hierarchical decomposition is a useful way of assessing structural complexity changes of organisms modeled as automata, and we show how recently developed computational tools can be used for this purpose, by computing holonomy decompositions and holonomy complexity. To gain insight into the evolution of complexity, we investigate the smoothness of the landscape structure of complexity under minimal transitions. As a proof of concept, we illustrate how the hierarchical complexity analysis reveals symmetries and irreversible structure in biological networks by applying the methods to the lac operon mechanism in the genetic regulatory network of Escherichia coli.
Dissipative quantum trajectories in complex space: Damped harmonic oscillator
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chou, Chia-Chun, E-mail: ccchou@mx.nthu.edu.tw
Dissipative quantum trajectories in complex space are investigated in the framework of the logarithmic nonlinear Schrödinger equation. The logarithmic nonlinear Schrödinger equation provides a phenomenological description for dissipative quantum systems. Substituting the wave function expressed in terms of the complex action into the complex-extended logarithmic nonlinear Schrödinger equation, we derive the complex quantum Hamilton–Jacobi equation including the dissipative potential. It is shown that dissipative quantum trajectories satisfy a quantum Newtonian equation of motion in complex space with a friction force. Exact dissipative complex quantum trajectories are analyzed for the wave and solitonlike solutions to the logarithmic nonlinear Schrödinger equation formore » the damped harmonic oscillator. These trajectories converge to the equilibrium position as time evolves. It is indicated that dissipative complex quantum trajectories for the wave and solitonlike solutions are identical to dissipative complex classical trajectories for the damped harmonic oscillator. This study develops a theoretical framework for dissipative quantum trajectories in complex space.« less
Lemmens, Karen; De Bie, Tijl; Dhollander, Thomas; De Keersmaecker, Sigrid C; Thijs, Inge M; Schoofs, Geert; De Weerdt, Ami; De Moor, Bart; Vanderleyden, Jos; Collado-Vides, Julio; Engelen, Kristof; Marchal, Kathleen
2009-01-01
We present DISTILLER, a data integration framework for the inference of transcriptional module networks. Experimental validation of predicted targets for the well-studied fumarate nitrate reductase regulator showed the effectiveness of our approach in Escherichia coli. In addition, the condition dependency and modularity of the inferred transcriptional network was studied. Surprisingly, the level of regulatory complexity seemed lower than that which would be expected from RegulonDB, indicating that complex regulatory programs tend to decrease the degree of modularity.
Gaiti, Federico; Jindrich, Katia; Fernandez-Valverde, Selene L; Roper, Kathrein E; Degnan, Bernard M; Tanurdžić, Miloš
2017-01-01
Combinatorial patterns of histone modifications regulate developmental and cell type-specific gene expression and underpin animal complexity, but it is unclear when this regulatory system evolved. By analysing histone modifications in a morphologically-simple, early branching animal, the sponge Amphimedonqueenslandica, we show that the regulatory landscape used by complex bilaterians was already in place at the dawn of animal multicellularity. This includes distal enhancers, repressive chromatin and transcriptional units marked by H3K4me3 that vary with levels of developmental regulation. Strikingly, Amphimedon enhancers are enriched in metazoan-specific microsyntenic units, suggesting that their genomic location is extremely ancient and likely to place constraints on the evolution of surrounding genes. These results suggest that the regulatory foundation for spatiotemporal gene expression evolved prior to the divergence of sponges and eumetazoans, and was necessary for the evolution of animal multicellularity. DOI: http://dx.doi.org/10.7554/eLife.22194.001 PMID:28395144
Regulatory issues for computerized electrocardiographic devices.
Muni, Neal I; Ho, Charles; Mallis, Elias
2004-01-01
Computerized electrocardiogram (ECG) devices are regulated in the U.S. by the FDA Center for Devices and Radiological Health (CDRH). This article aims to highlight the salient points of the FDA regulatory review process, including the important distinction between a "tool" claim and a "clinical" claim in the intended use of a computerized ECG device. Specifically, a tool claim relates to the ability of the device to accurately measure a certain ECG parameter, such as T-wave alternans (TWA), while a clinical claim imputes a particular health hazard associated with the identified parameter, such as increased risk of ventricular tachyarrhythmia or sudden death. Given that both types of claims are equally important and receive the same regulatory scrutiny, the manufacturer of a new ECG diagnostic device should consider the distinction and regulatory pathways for approval between the two types of claims discussed in this paper.
Rogue waves in terms of multi-point statistics and nonequilibrium thermodynamics
NASA Astrophysics Data System (ADS)
Hadjihosseini, Ali; Lind, Pedro; Mori, Nobuhito; Hoffmann, Norbert P.; Peinke, Joachim
2017-04-01
Ocean waves, which lead to rogue waves, are investigated on the background of complex systems. In contrast to deterministic approaches based on the nonlinear Schroedinger equation or focusing effects, we analyze this system in terms of a noisy stochastic system. In particular we present a statistical method that maps the complexity of multi-point data into the statistics of hierarchically ordered height increments for different time scales. We show that the stochastic cascade process with Markov properties is governed by a Fokker-Planck equation. Conditional probabilities as well as the Fokker-Planck equation itself can be estimated directly from the available observational data. This stochastic description enables us to show several new aspects of wave states. Surrogate data sets can in turn be generated allowing to work out different statistical features of the complex sea state in general and extreme rogue wave events in particular. The results also open up new perspectives for forecasting the occurrence probability of extreme rogue wave events, and even for forecasting the occurrence of individual rogue waves based on precursory dynamics. As a new outlook the ocean wave states will be considered in terms of nonequilibrium thermodynamics, for which the entropy production of different wave heights will be considered. We show evidence that rogue waves are characterized by negative entropy production. The statistics of the entropy production can be used to distinguish different wave states.
Federal Register 2010, 2011, 2012, 2013, 2014
2012-05-04
... conditions), the regulatory constraints and mitigation requirements for unavoidable impacts to coral reefs..., habitat surveys, and wave response modeling. The public may request copies of reports. The public will be...
Gao, Yingjie; Zhang, Jinhai; Yao, Zhenxing
2015-12-01
The complex frequency shifted perfectly matched layer (CFS-PML) can improve the absorbing performance of PML for nearly grazing incident waves. However, traditional PML and CFS-PML are based on first-order wave equations; thus, they are not suitable for second-order wave equation. In this paper, an implementation of CFS-PML for second-order wave equation is presented using auxiliary differential equations. This method is free of both convolution calculations and third-order temporal derivatives. As an unsplit CFS-PML, it can reduce the nearly grazing incidence. Numerical experiments show that it has better absorption than typical PML implementations based on second-order wave equation.
Mitotic trigger waves and the spatial coordination of the Xenopus cell cycle.
Chang, Jeremy B; Ferrell, James E
2013-08-29
Despite the large size of the Xenopus laevis egg (approximately 1.2 mm diameter), a fertilized egg rapidly proceeds through mitosis in a spatially coordinated fashion. Mitosis is initiated by a bistable system of regulatory proteins centred on Cdk1 (refs 1, 2), raising the possibility that this spatial coordination could be achieved through trigger waves of Cdk1 activity. Using an extract system that performs cell cycles in vitro, here we show that mitosis does spread through Xenopus cytoplasm via trigger waves, propagating at a linear speed of approximately 60 µm min(-1). Perturbing the feedback loops that give rise to the bistability of Cdk1 changes the speed and dynamics of the waves. Time-lapse imaging of intact eggs argues that trigger waves of Cdk1 activation are responsible for surface contraction waves, ripples in the cell cortex that precede cytokinesis. These findings indicate that Cdk1 trigger waves help ensure the spatiotemporal coordination of mitosis in large eggs. Trigger waves may be an important general mechanism for coordinating biochemical events over large distances.
Capturing rogue waves by multi-point statistics
NASA Astrophysics Data System (ADS)
Hadjihosseini, A.; Wächter, Matthias; Hoffmann, N. P.; Peinke, J.
2016-01-01
As an example of a complex system with extreme events, we investigate ocean wave states exhibiting rogue waves. We present a statistical method of data analysis based on multi-point statistics which for the first time allows the grasping of extreme rogue wave events in a highly satisfactory statistical manner. The key to the success of the approach is mapping the complexity of multi-point data onto the statistics of hierarchically ordered height increments for different time scales, for which we can show that a stochastic cascade process with Markov properties is governed by a Fokker-Planck equation. Conditional probabilities as well as the Fokker-Planck equation itself can be estimated directly from the available observational data. With this stochastic description surrogate data sets can in turn be generated, which makes it possible to work out arbitrary statistical features of the complex sea state in general, and extreme rogue wave events in particular. The results also open up new perspectives for forecasting the occurrence probability of extreme rogue wave events, and even for forecasting the occurrence of individual rogue waves based on precursory dynamics.
Few-cycle optical rogue waves: complex modified Korteweg-de Vries equation.
He, Jingsong; Wang, Lihong; Li, Linjing; Porsezian, K; Erdélyi, R
2014-06-01
In this paper, we consider the complex modified Korteweg-de Vries (mKdV) equation as a model of few-cycle optical pulses. Using the Lax pair, we construct a generalized Darboux transformation and systematically generate the first-, second-, and third-order rogue wave solutions and analyze the nature of evolution of higher-order rogue waves in detail. Based on detailed numerical and analytical investigations, we classify the higher-order rogue waves with respect to their intrinsic structure, namely, fundamental pattern, triangular pattern, and ring pattern. We also present several new patterns of the rogue wave according to the standard and nonstandard decomposition. The results of this paper explain the generalization of higher-order rogue waves in terms of rational solutions. We apply the contour line method to obtain the analytical formulas of the length and width of the first-order rogue wave of the complex mKdV and the nonlinear Schrödinger equations. In nonlinear optics, the higher-order rogue wave solutions found here will be very useful to generate high-power few-cycle optical pulses which will be applicable in the area of ultrashort pulse technology.
NASA Astrophysics Data System (ADS)
Nurhandoko, Bagus Endar B.; Sukmana, Indriani; Mubarok, Syahrul; Deny, Agus; Widowati, Sri; Kurniadi, Rizal
2012-06-01
Migration is important issue for seismic imaging in complex structure. In this decade, depth imaging becomes important tools for producing accurate image in depth imaging instead of time domain imaging. The challenge of depth migration method, however, is in revealing the complex structure of subsurface. There are many methods of depth migration with their advantages and weaknesses. In this paper, we show our propose method of pre-stack depth migration based on time domain inverse scattering wave equation. Hopefully this method can be as solution for imaging complex structure in Indonesia, especially in rich thrusting fault zones. In this research, we develop a recent advance wave equation migration based on time domain inverse scattering wave which use more natural wave propagation using scattering wave. This wave equation pre-stack depth migration use time domain inverse scattering wave equation based on Helmholtz equation. To provide true amplitude recovery, an inverse of divergence procedure and recovering transmission loss are considered of pre-stack migration. Benchmarking the propose inverse scattering pre-stack depth migration with the other migration methods are also presented, i.e.: wave equation pre-stack depth migration, waveequation depth migration, and pre-stack time migration method. This inverse scattering pre-stack depth migration could image successfully the rich fault zone which consist extremely dip and resulting superior quality of seismic image. The image quality of inverse scattering migration is much better than the others migration methods.
NASA Astrophysics Data System (ADS)
Calderer, Antoni; Guo, Xin; Shen, Lian; Sotiropoulos, Fotis
2018-02-01
We develop a numerical method for simulating coupled interactions of complex floating structures with large-scale ocean waves and atmospheric turbulence. We employ an efficient large-scale model to develop offshore wind and wave environmental conditions, which are then incorporated into a high resolution two-phase flow solver with fluid-structure interaction (FSI). The large-scale wind-wave interaction model is based on a two-fluid dynamically-coupled approach that employs a high-order spectral method for simulating the water motion and a viscous solver with undulatory boundaries for the air motion. The two-phase flow FSI solver is based on the level set method and is capable of simulating the coupled dynamic interaction of arbitrarily complex bodies with airflow and waves. The large-scale wave field solver is coupled with the near-field FSI solver with a one-way coupling approach by feeding into the latter waves via a pressure-forcing method combined with the level set method. We validate the model for both simple wave trains and three-dimensional directional waves and compare the results with experimental and theoretical solutions. Finally, we demonstrate the capabilities of the new computational framework by carrying out large-eddy simulation of a floating offshore wind turbine interacting with realistic ocean wind and waves.
Directional control of WAVE2 membrane targeting by EB1 and phosphatidylinositol 3,4,5-triphosphate.
Takahashi, Kazuhide; Tanaka, Tacu; Suzuki, Katsuo
2010-03-01
Membrane targeting of WAVE2 along microtubules is mediated by a motor protein kinesin and requires Pak1, a downstream effector of Rac1. However, the mechanism by which WAVE2 targeting to the leading edge is directionally controlled remains largely unknown. Here we demonstrate that EB1, a microtubule plus-end-binding protein, constitutively associates with stathmin, a microtubule-destabilizing protein, in human breast cancer cells. Stimulation of the cells with insulin-like growth factor I (IGF-I) induced Pak1-dependent binding of the EB1-stathmin complex to microtubules that bear WAVE2 and colocalization of the complex with WAVE2 at the leading edge. Depletion of EB1 by small interfering RNA (siRNA) abrogated the IGF-I-induced WAVE2 targeting and stathmin binding to microtubules. On the other hand, chemotaxis chamber assays indicated that the IGF-I receptor (IGF-IR) was locally activated in the region facing toward IGF-I. In addition, IGF-I caused phosphatidylinositol 3-kinase (PI 3-kinase)-dependent production of phosphatidylinositol 3,4,5-triphosphate (PIP3) near activated IGF-IR and WAVE2 colocalization with it. Collectively, WAVE2-membrane targeting is directionally controlled by binding of the EB1-stathmin complex to WAVE2-bearing microtubules and by the interaction between WAVE2 and PIP3 produced near IGF-IR that is locally activated by IGF-I.
3-D FDTD simulation of shear waves for evaluation of complex modulus imaging.
Orescanin, Marko; Wang, Yue; Insana, Michael
2011-02-01
The Navier equation describing shear wave propagation in 3-D viscoelastic media is solved numerically with a finite differences time domain (FDTD) method. Solutions are formed in terms of transverse scatterer velocity waves and then verified via comparison to measured wave fields in heterogeneous hydrogel phantoms. The numerical algorithm is used as a tool to study the effects on complex shear modulus estimation from wave propagation in heterogeneous viscoelastic media. We used an algebraic Helmholtz inversion (AHI) technique to solve for the complex shear modulus from simulated and experimental velocity data acquired in 2-D and 3-D. Although 3-D velocity estimates are required in general, there are object geometries for which 2-D inversions provide accurate estimations of the material properties. Through simulations and experiments, we explored artifacts generated in elastic and dynamic-viscous shear modulus images related to the shear wavelength and average viscosity.
Tuominen, H; Salminen, A; Oksanen, E; Jämsen, J; Heikkilä, O; Lehtiö, L; Magretova, N N; Goldman, A; Baykov, A A; Lahti, R
2010-05-07
Nucleotide-binding cystathionine beta-synthase (CBS) domains serve as regulatory units in numerous proteins distributed in all kingdoms of life. However, the underlying regulatory mechanisms remain to be established. Recently, we described a subfamily of CBS domain-containing pyrophosphatases (PPases) within family II PPases. Here, we express a novel CBS-PPase from Clostridium perfringens (CPE2055) and show that the enzyme is inhibited by AMP and activated by a novel effector, diadenosine 5',5-P1,P4-tetraphosphate (AP(4)A). The structures of the AMP and AP(4)A complexes of the regulatory region of C. perfringens PPase (cpCBS), comprising a pair of CBS domains interlinked by a DRTGG domain, were determined at 2.3 A resolution using X-ray crystallography. The structures obtained are the first structures of a DRTGG domain as part of a larger protein structure. The AMP complex contains two AMP molecules per cpCBS dimer, each bound to a single monomer, whereas in the activator-bound complex, one AP(4)A molecule bridges two monomers. In the nucleotide-bound structures, activator binding induces significant opening of the CBS domain interface, compared with the inhibitor complex. These results provide structural insight into the mechanism of CBS-PPase regulation by nucleotides. Copyright 2010 Elsevier Ltd. All rights reserved.
Lemmens, Karen; De Bie, Tijl; Dhollander, Thomas; De Keersmaecker, Sigrid C; Thijs, Inge M; Schoofs, Geert; De Weerdt, Ami; De Moor, Bart; Vanderleyden, Jos; Collado-Vides, Julio; Engelen, Kristof; Marchal, Kathleen
2009-01-01
We present DISTILLER, a data integration framework for the inference of transcriptional module networks. Experimental validation of predicted targets for the well-studied fumarate nitrate reductase regulator showed the effectiveness of our approach in Escherichia coli. In addition, the condition dependency and modularity of the inferred transcriptional network was studied. Surprisingly, the level of regulatory complexity seemed lower than that which would be expected from RegulonDB, indicating that complex regulatory programs tend to decrease the degree of modularity. PMID:19265557
Regulatory and clinical considerations for biosimilar oncology drugs
Bennett, Charles L; Chen, Brian; Hermanson, Terhi; Wyatt, Michael D; Schulz, Richard M; Georgantopoulos, Peter; Kessler, Samuel; Raisch, Dennis W; Qureshi, Zaina P; Lu, Z Kevin; Love, Bryan L; Noxon, Virginia; Bobolts, Laura; Armitage, Melissa; Bian, John; Ray, Paul; Ablin, Richard J; Hrushesky, William J; Macdougall, Iain C; Sartor, Oliver; Armitage, James O
2015-01-01
Biological oncology products are integral to cancer treatment, but their high costs pose challenges to patients, families, providers, and insurers. The introduction of biosimilar agents—molecules that are similar in structure, function, activity, immunogenicity, and safety to the original biological drugs—provide opportunities both to improve healthcare access and outcomes, and to reduce costs. Several international regulatory pathways have been developed to expedite entry of biosimilars into global marketplaces. The first wave of oncology biosimilar use was in Europe and India in 2007. Oncology biosimilars are now widely marketed in several countries in Europe, and in Australia, Japan, China, Russia, India, and South Korea. Their use is emerging worldwide, with the notable exception of the USA, where several regulatory and cost barriers to biosimilar approval exist. In this Review, we discuss oncology biosimilars and summarise their regulatory frameworks, clinical experiences, and safety concerns. PMID:25456378
MicroRNA-mediated regulatory circuits: outlook and perspectives
NASA Astrophysics Data System (ADS)
Cora', Davide; Re, Angela; Caselle, Michele; Bussolino, Federico
2017-08-01
MicroRNAs have been found to be necessary for regulating genes implicated in almost all signaling pathways, and consequently their dysfunction influences many diseases, including cancer. Understanding of the complexity of the microRNA-mediated regulatory network has grown in terms of size, connectivity and dynamics with the development of computational and, more recently, experimental high-throughput approaches for microRNA target identification. Newly developed studies on recurrent microRNA-mediated circuits in regulatory networks, also known as network motifs, have substantially contributed to addressing this complexity, and therefore to helping understand the ways by which microRNAs achieve their regulatory role. This review provides a summarizing view of the state-of-the-art, and perspectives of research efforts on microRNA-mediated regulatory motifs. In this review, we discuss the topological properties characterizing different types of circuits, and the regulatory features theoretically enabled by such properties, with a special emphasis on examples of circuits typifying their biological significance in experimentally validated contexts. Finally, we will consider possible future developments, in particular regarding microRNA-mediated circuits involving long non-coding RNAs and epigenetic regulators.
The complexity of gene expression dynamics revealed by permutation entropy
2010-01-01
Background High complexity is considered a hallmark of living systems. Here we investigate the complexity of temporal gene expression patterns using the concept of Permutation Entropy (PE) first introduced in dynamical systems theory. The analysis of gene expression data has so far focused primarily on the identification of differentially expressed genes, or on the elucidation of pathway and regulatory relationships. We aim to study gene expression time series data from the viewpoint of complexity. Results Applying the PE complexity metric to abiotic stress response time series data in Arabidopsis thaliana, genes involved in stress response and signaling were found to be associated with the highest complexity not only under stress, but surprisingly, also under reference, non-stress conditions. Genes with house-keeping functions exhibited lower PE complexity. Compared to reference conditions, the PE of temporal gene expression patterns generally increased upon stress exposure. High-complexity genes were found to have longer upstream intergenic regions and more cis-regulatory motifs in their promoter regions indicative of a more complex regulatory apparatus needed to orchestrate their expression, and to be associated with higher correlation network connectivity degree. Arabidopsis genes also present in other plant species were observed to exhibit decreased PE complexity compared to Arabidopsis specific genes. Conclusions We show that Permutation Entropy is a simple yet robust and powerful approach to identify temporal gene expression profiles of varying complexity that is equally applicable to other types of molecular profile data. PMID:21176199
NASA Astrophysics Data System (ADS)
Wang, Yu; Chou, Chia-Chun
2018-05-01
The coupled complex quantum Hamilton-Jacobi equations for electronic nonadiabatic transitions are approximately solved by propagating individual quantum trajectories in real space. Equations of motion are derived through use of the derivative propagation method for the complex actions and their spatial derivatives for wave packets moving on each of the coupled electronic potential surfaces. These equations for two surfaces are converted into the moving frame with the same grid point velocities. Excellent wave functions can be obtained by making use of the superposition principle even when nodes develop in wave packet scattering.
Electrocardiogram of Clinically Healthy Mithun (Bos frontalis): Variation among Strains
Sanyal, Sagar; Das, Pradip Kumar; Ghosh, Probal Ranjan; Das, Kinsuk; Vupru, Kezha V.; Rajkhowa, Chandan; Mondal, Mohan
2010-01-01
A study was conducted to establish the normal electrocardiogram in four different genetic strains of mithun (Bos frontalis). Electrocardiography, cardiac electrical axis, heart rate, rectal temperature and respiration rate were recorded in a total of 32 adult male mithun of four strains (n = 8 each). It was found that the respiration and heart rates were higher (P < .05) in Manipur than other three strains. Amplitude (P < .05) and duration of P wave and QRS complex differed (P < .01) among the strains. Mizoram strain had the highest amplitude and duration of P wave and QRS complex. On the other hand, higher (P < .05) amplitude and duration of T wave were recorded in Arunachalee and Mizoram strains. The mean electrical axis of QRS complex that were recorded for Arunachalee and Manipur strains were similar to that reported for other bovine species; whereas the electrical axis of QRS for Nagamese and Mizoram strains were more close to feline and caprine species, respectively. In conclusion, electrocardiogram of mithun revealed that the amplitude and duration of P wave, QRS complex and T wave were different among four different genetic strains of mithun and the electrical axis of QRS complex for Nagamese and Mizoram mithuns are dissimilar to bovine species. PMID:20886013
Wolff-Parkinson-White (WPW) syndrome: the detection of delta wave in an electrocardiogram (ECG).
Mahamat, Hassan Adam; Jacquir, Sabir; Khalil, Cliff; Laurent, Gabriel; Binczak, Stephane
2016-08-01
The delta wave remains an important indicator to diagnose the WPW syndrome. In this paper, a new method of detection of delta wave in an ECG signal is proposed. Firstly, using the continuous wavelet transform, the P wave, the QRS complex and the T wave are detected, then their durations are computed after determination of the boundary location (onsets and offsets of the P, QRS and T waves). Secondly, the PR duration, the QRS duration and the upstroke of the QRS complex are used to determine the presence or absence of the delta wave. This algorithm has been tested on the Physionel database (ptbdb) in order to evaluate its robustness. It has been applied to clinical signals from patients affected by WPW syndrome. This method can provide assistance to practitioners in order to detect the WPW syndrome.
Huang, Dandan; Yi, Xianfu; Zhang, Shijie; Zheng, Zhanye; Wang, Panwen; Xuan, Chenghao; Sham, Pak Chung; Wang, Junwen; Li, Mulin Jun
2018-05-16
Genome-wide association studies have generated over thousands of susceptibility loci for many human complex traits, and yet for most of these associations the true causal variants remain unknown. Tissue/cell type-specific prediction and prioritization of non-coding regulatory variants will facilitate the identification of causal variants and underlying pathogenic mechanisms for particular complex diseases and traits. By leveraging recent large-scale functional genomics/epigenomics data, we develop an intuitive web server, GWAS4D (http://mulinlab.tmu.edu.cn/gwas4d or http://mulinlab.org/gwas4d), that systematically evaluates GWAS signals and identifies context-specific regulatory variants. The updated web server includes six major features: (i) updates the regulatory variant prioritization method with our new algorithm; (ii) incorporates 127 tissue/cell type-specific epigenomes data; (iii) integrates motifs of 1480 transcriptional regulators from 13 public resources; (iv) uniformly processes Hi-C data and generates significant interactions at 5 kb resolution across 60 tissues/cell types; (v) adds comprehensive non-coding variant functional annotations; (vi) equips a highly interactive visualization function for SNP-target interaction. Using a GWAS fine-mapped set for 161 coronary artery disease risk loci, we demonstrate that GWAS4D is able to efficiently prioritize disease-causal regulatory variants.
Germline Stem Cells: Origin and Destiny
Lehmann, Ruth
2012-01-01
Germline stem cells are key to genome transmission to future generations. Over recent years, there have been numerous insights into the regulatory mechanisms that govern both germ cell specification and the maintenance of the germline in adults. Complex regulatory interactions with both the niche and the environment modulate germline stem cell function. This perspective highlights some examples of this regulation to illustrate the diversity and complexity of the mechanisms involved. PMID:22704513
Li, Zhengkai; Lee, Kenneth; King, Thomas; Boufadel, Michel C; Venosa, Albert D
2009-05-01
Testing dispersant effectiveness under conditions similar to that of the open environment is required for improvements in operational procedures and the formulation of regulatory guidelines. To this end, a novel wave tank facility was fabricated to study the dispersion of crude oil under regular non-breaking and irregular breaking wave conditions. This wave tank facility was designed for operation in a flow-through mode to simulate both wave- and current-driven hydrodynamic conditions. We report here an evaluation of the effectiveness of chemical dispersants (Corexit EC9500A and SPC 1000) on two crude oils (Medium South American [MESA] and Alaska North Slope [ANS]) under two different wave conditions (regular non-breaking and plunging breaking waves) in this wave tank. The dispersant effectiveness was assessed by measuring the water column oil concentration and dispersed oil droplet size distribution. In the absence of dispersants, nearly 8-19% of the test crude oils were dispersed and diluted under regular wave and breaking wave conditions. In the presence of dispersants, about 21-36% of the crude oils were dispersed and diluted under regular waves, and 42-62% under breaking waves. Consistently, physical dispersion under regular waves produced large oil droplets (volumetric mean diameter or VMD > or = 300 microm), whereas chemical dispersion under breaking waves created small droplets (VMD < or = 50 microm). The data can provide useful information for developing better operational guidelines for dispersant use and improved predictive models on dispersant effectiveness in the field.
WAVE binds Ena/VASP for enhanced Arp2/3 complex–based actin assembly
Havrylenko, Svitlana; Noguera, Philippe; Abou-Ghali, Majdouline; Manzi, John; Faqir, Fahima; Lamora, Audrey; Guérin, Christophe; Blanchoin, Laurent; Plastino, Julie
2015-01-01
The WAVE complex is the main activator of the Arp2/3 complex for actin filament nucleation and assembly in the lamellipodia of moving cells. Other important players in lamellipodial protrusion are Ena/VASP proteins, which enhance actin filament elongation. Here we examine the molecular coordination between the nucleating activity of the Arp2/3 complex and the elongating activity of Ena/VASP proteins for the formation of actin networks. Using an in vitro bead motility assay, we show that WAVE directly binds VASP, resulting in an increase in Arp2/3 complex–based actin assembly. We show that this interaction is important in vivo as well, for the formation of lamellipodia during the ventral enclosure event of Caenorhabditis elegans embryogenesis. Ena/VASP's ability to bind F-actin and profilin-complexed G-actin are important for its effect, whereas Ena/VASP tetramerization is not necessary. Our data are consistent with the idea that binding of Ena/VASP to WAVE potentiates Arp2/3 complex activity and lamellipodial actin assembly. PMID:25355952
Characterization of new regulatory elements within the Drosophila bithorax complex.
Pérez-Lluch, Sílvia; Cuartero, Sergi; Azorín, Fernando; Espinàs, M Lluïsa
2008-12-01
The homeotic Abdominal-B (Abd-B) gene expression depends on a modular cis-regulatory region divided into discrete functional domains (iab) that control the expression of the gene in a particular segment of the fly. These domains contain regulatory elements implicated in both initiation and maintenance of homeotic gene expression and elements that separate the different domains. In this paper we have performed an extensive analysis of the iab-6 regulatory region, which regulates Abd-B expression at abdominal segment A6 (PS11), and we have characterized two new polycomb response elements (PREs) within this domain. We report that PREs at Abd-B cis-regulatory domains present a particular chromatin structure which is nuclease accessible all along Drosophila development and both in active and repressed states. We also show that one of these regions contains a dCTCF and CP190 dependent activity in transgenic enhancer-blocking assays, suggesting that it corresponds to the Fab-6 boundary element of the Drosophila bithorax complex.
Coulomb wave functions with complex values of the variable and the parameters
NASA Astrophysics Data System (ADS)
Dzieciol, Aleksander; Yngve, Staffan; Fröman, Per Olof
1999-12-01
The motivation for the present paper lies in the fact that the literature concerning the Coulomb wave functions FL(η,ρ) and GL(η,ρ) is a jungle in which it may be hard to find a safe way when one needs general formulas for the Coulomb wave functions with complex values of the variable ρ and the parameters L and η. For the Coulomb wave functions and certain linear combinations of these functions we discuss the connection with the Whittaker function, the Coulomb phase shift, Wronskians, reflection formulas (L→-L-1), integral representations, series expansions, circuital relations (ρ→ρe±iπ) and asymptotic formulas on a Riemann surface for the variable ρ. The parameters L and η are allowed to assume complex values.
Generative complexity of Gray-Scott model
NASA Astrophysics Data System (ADS)
Adamatzky, Andrew
2018-03-01
In the Gray-Scott reaction-diffusion system one reactant is constantly fed in the system, another reactant is reproduced by consuming the supplied reactant and also converted to an inert product. The rate of feeding one reactant in the system and the rate of removing another reactant from the system determine configurations of concentration profiles: stripes, spots, waves. We calculate the generative complexity-a morphological complexity of concentration profiles grown from a point-wise perturbation of the medium-of the Gray-Scott system for a range of the feeding and removal rates. The morphological complexity is evaluated using Shannon entropy, Simpson diversity, approximation of Lempel-Ziv complexity, and expressivity (Shannon entropy divided by space-filling). We analyse behaviour of the systems with highest values of the generative morphological complexity and show that the Gray-Scott systems expressing highest levels of the complexity are composed of the wave-fragments (similar to wave-fragments in sub-excitable media) and travelling localisations (similar to quasi-dissipative solitons and gliders in Conway's Game of Life).
Nonlinear excited waves on the interventricular septum
NASA Astrophysics Data System (ADS)
Bekki, Naoaki; Harada, Yoshifumi; Kanai, Hiroshi
2012-11-01
Using a novel ultrasonic noninvasive imaging method, we observe some phase singularities in propagating excited waves on a human cardiac interventricular septum (IVS) for a healthy young male. We present a possible physical model explaining one-dimensional dynamics of phase singularities in nonlinearly excited waves on the IVS. We show that at least one of the observed phase singularities in the excited waves on the IVS can be explained by the Bekki-Nozaki hole solution of the complex Ginzburg-Landau equation without any adjustable parameters. We conclude that the complex Ginzburg-Landau equation is such a suitable model for one-dimensional dynamics of cardiac phase singularities in nonlinearly excited waves on the IVS.
Morton, R.A.; Richmond, B.M.; Jaffe, B.E.; Gelfenbaum, G.
2008-01-01
Coastal gravel-ridge complexes deposited on islands in the Caribbean Sea are recorders of past extreme-wave events that could be associated with either tsunamis or hurricanes. The ridge complexes of Bonaire, Jamaica, Puerto Rico (Isla de Mona), and Guadeloupe consist of polymodal clasts ranging in size from sand to coarse boulders that are derived from the adjacent coral reefs or subjacent rock platforms. Ridge-complex morphologies and crest elevations are largely controlled by availability of sediments, clast sizes, and heights of wave runup. The ridge complexes are internally organized, display textural sorting and a broad range of ages including historical events. Some display seaward-dipping beds and ridge-and-swale topography, and some terminate in fans or steep avalanche slopes. Together, the morphologic, sedimentologic, lithostratigraphic, and chronostratigraphic evidence indicates that shore-parallet ridge complexes composed of gravel and sand that are tens of meters wide and several meters thick are primarily storm-constructed features that have accumulated for a few centuries or millennia as a result of multiple high-frequency intense-wave events. They are not entirely the result of one or a few tsunamis as recently reported. Tsunami deposition may account for some of the lateral ridge-complex accretion or boulder fields and isolated blocks that are associated with the ridge complexes. Copyright ?? 2008, SEPM (Society for Sedimentary Geology).
Numerical Modeling of Geomorphic Change on Sandy Coasts as a Function of Changing Wave Climate
NASA Astrophysics Data System (ADS)
Adams, P. N.; McNamara, D.; Murray, A. B.; Lovering, J.
2009-12-01
Climate change is expected to affect sandy coast geomorphology through two principal mechanisms: (1) sea level rise, which affects cross-shore sediment transport tending to drive shoreline retreat, and (2) alteration of statistical distributions in ocean storm wave climate (deep water wave height, period, and direction), which affects longshore sediment transport gradients that result in shoreline erosion and accretion. To address potential climate change-driven effects on longshore sediment transport gradients, we are developing techniques to link various numerical models of wave transformation with several different longshore sediment transport formulae in accordance with the Community Surface Dynamics Modeling System (CSDMS) project. Results of the various wave transformation models are compared to field observations of cross-shelf wave transformation along the North Florida Atlantic coast for purposes of model verification and calibration. Initial comparisons between wave-transformation methods (assumption of shore-parallel contours, simple wave ray tracing, and the SWAN spectral wave model) on artificially constructed continental shelves reveal an increasing discrepancy of results for increasing complexity of shelf bathymetry. When the more advanced SWAN spectral wave model is coupled with a simple CERC-type formulation of longshore sediment transport and applied to a real coast with complex offshore shoals (Cape Canaveral region of the North Florida Atlantic Coast), the patterns of erosion and accretion agree with results of the simplest wave-propagation models for some wave conditions, but disagree in others. Model simulations in which wave height and period are held constant show that locations of divergence and convergence of sediment flux shift with deep water wave-approach angle in ways that would not always be predicted using less sophisticated wave propagation models. Thus, predicting long-term local shoreline change on actual coastlines featuring complex bathymetry requires the extra computational effort to run the more advanced model over a wide range of wave conditions.
Hoeke, R.; Storlazzi, C.; Ridd, P.
2011-01-01
This paper examines the relationship between offshore wave climate and nearshore waves and currents at Hanalei Bay, Hawaii, an exposed bay fringed with coral reefs. Analysis of both offshore in situ data and numerical hindcasts identify the predominance of two wave conditions: a mode associated with local trade winds and an episodic pattern associated with distant source long-period swells. Analysis of 10 months of in situ data within the bay show that current velocities are up to an order of magnitude greater during long-period swell episodes than during trade wind conditions; overall circulation patterns are also fundamentally different. The current velocities are highly correlated with incident wave heights during the swell episodes, while they are not during the modal trade wind conditions. A phase-averaged wave model was implemented with the dual purpose of evaluating application to bathymetrically complex fringing reefs and to examine the propagation of waves into the nearshore in an effort to better explain the large difference in observed circulation during the two offshore wave conditions. The prediction quality of this model was poorer for the episodic condition than for the lower-energy mode, however, it illustrated how longer-period swells are preferentially refracted into the bay and make available far more nearshore wave energy to drive currents compared to waves during modal conditions. The highly episodic circulation, the nature of which is dependent on complex refraction patterns of episodic, long-period swell has implications for flushing and sediment dynamics for incised fringing reef-lined bays that characterize many high islands at low latitudes around the world.
Reflection and interference of electromagnetic waves in inhomogeneous media
NASA Technical Reports Server (NTRS)
Geiger, F. E.; Kyle, H. L.
1973-01-01
Solutions were obtained of the wave equation for a plane horizontally polarized electro-magnetic wave incident on a semi infinite two dimensional inhomogeneous medium. Two problems were considered: An inhomogeneous half space, and an inhomogeneous layer of arbitrary thickness. Solutions of the wave equation were obtained in terms of Hankel functions with complex arguments. Numerical calculations were made of the reflection coefficient R at the interface of the homogeneous medium. The startling results show that the reflection coefficient for a complex dielectric constant with gradient, can be less than that of the same medium with zero gradient.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zuo, Peng; Fan, Zheng, E-mail: ZFAN@ntu.edu.sg; Zhou, Yu
2016-07-15
Nonlinear guided waves have been investigated widely in simple geometries, such as plates, pipe and shells, where analytical solutions have been developed. This paper extends the application of nonlinear guided waves to waveguides with arbitrary cross sections. The criteria for the existence of nonlinear guided waves were summarized based on the finite deformation theory and nonlinear material properties. Numerical models were developed for the analysis of nonlinear guided waves in complex geometries, including nonlinear Semi-Analytical Finite Element (SAFE) method to identify internal resonant modes in complex waveguides, and Finite Element (FE) models to simulate the nonlinear wave propagation at resonantmore » frequencies. Two examples, an aluminum plate and a steel rectangular bar, were studied using the proposed numerical model, demonstrating the existence of nonlinear guided waves in such structures and the energy transfer from primary to secondary modes.« less
Requirement of the basic region of N-WASP/WAVE2 for actin-based motility.
Suetsugu, S; Miki, H; Yamaguchi, H; Takenawa, T
2001-04-06
WASP family proteins activate nucleation by the Arp2/3 complex, inducing rapid actin polymerization in vitro. Although the C-terminal portion of WASP family proteins (VCA) activates nucleation by the Arp2/3 complex in pure systems, we find that this fragment lacks activity in cell extracts. Thus, polystyrene beads coated with VCA did not move in brain cytosol, while beads coated with N-WASP or WAVE2 did move. The basic clusters between the WH1 domain and the CRIB domain of N-WASP were critical for movement since beads coated with N-WASP or WAVE2 constructs missing the basic clusters (Delta basic) also did not move. Furthermore, VCA and N-WASP/WAVE2 Delta basic constructs were much less able than wild-type N-WASP and WAVE2 to induce actin polymerization in cytosol. All of the proteins, with or without the basic domain, were potent activators of nucleation by purified Arp2/3 complex. Copyright 2001 Academic Press.
Structure Formation in Complex Plasma - Quantum Effects in Cryogenic Complex Plasmas
2014-09-26
pipe at the flange attached to the inner Dewar bottle. The temperature of the gas in the glass tube is controlled by the cryogenic liquid , liquid ...dust particles. The supersonic flow was possible to make in a complex plasma since dust acoustic wave is characterized by a sound speed of a few cm...through the illumination of laser light on dust particles. The supersonic flow was possible to make in a complex plasma since dust acoustic wave is
Comparing wave shoaling methods used in large-scale coastal evolution modeling
NASA Astrophysics Data System (ADS)
Limber, P. W.; Adams, P. N.; Murray, A.
2013-12-01
A variety of methods are available to simulate wave propagation from the deep ocean to the surf zone. They range from simple and computationally fast (e.g. linear wave theory applied to shore-parallel bathymetric contours) to complicated and computationally intense (e.g., Delft's ';Simulating WAves Nearshore', or SWAN, model applied to complex bathymetry). Despite their differences, the goal of each method is the same with respect to coastline evolution modeling: to link offshore waves with rates of (and gradients in) alongshore sediment transport. Choosing a shoaling technique for modeling coastline evolution should be partly informed by the spatial and temporal scales of the model, as well as the model's intent (is it simulating a specific coastline, or exploring generic coastline dynamics?). However, the particular advantages and disadvantages of each technique, and how the advantages/disadvantages vary over different model spatial and temporal scales, are not always clear. We present a wave shoaling model that simultaneously computes breaking wave heights and angles using three increasingly complex wave shoaling routines: the most basic approach assuming shore-parallel bathymetric contours, a wave ray tracing method that includes wave energy convergence and divergence and non-shore-parallel contours, and a spectral wave model (SWAN). Initial results show reasonable agreement between wave models along a flat shoreline for small (1 m) wave heights, low wave angles (0 to 10 degrees), and simple bathymetry. But, as wave heights and angles increase, bathymetry becomes more variable, and the shoreline shape becomes sinuous, the model results begin to diverge. This causes different gradients in alongshore sediment transport between model runs employing different shoaling techniques and, therefore, different coastline behavior. Because SWAN does not approximate wave breaking (which drives alongshore sediment transport) we use a routine to extract grid cells from SWAN output where wave height is approximately one-half of the water depth (a standard wave breaking threshold). The goal of this modeling exercise is to understand under what conditions a simple wave model is sufficient for simulating coastline evolution, and when using a more complex shoaling routine can optimize a coastline model. The Coastline Evolution Model (CEM; Ashton and Murray, 2006) is used to show how different shoaling routines affect modeled coastline behavior. The CEM currently includes the most basic wave shoaling approach to simulate cape and spit formation. We will instead couple it to SWAN, using the insight from the comprehensive wave model (above) to guide its application. This will allow waves transformed over complex bathymetry, such as cape-associated shoals and ridges, to be input for the CEM so that large-scale coastline behavior can be addressed in less idealized environments. Ashton, A., and Murray, A.B., 2006, High-angle wave instability and emergent shoreline shapes: 1. Modeling of sand waves, flying spits, and capes: Journal of Geophysical Research, v. 111, p. F04011, doi:10.1029/2005JF000422.
Some new traveling wave exact solutions of the (2+1)-dimensional Boiti-Leon-Pempinelli equations.
Qi, Jian-ming; Zhang, Fu; Yuan, Wen-jun; Huang, Zi-feng
2014-01-01
We employ the complex method to obtain all meromorphic exact solutions of complex (2+1)-dimensional Boiti-Leon-Pempinelli equations (BLP system of equations). The idea introduced in this paper can be applied to other nonlinear evolution equations. Our results show that all rational and simply periodic traveling wave exact solutions of the equations (BLP) are solitary wave solutions, the complex method is simpler than other methods, and there exist some rational solutions ur,2 (z) and simply periodic solutions us,2-6(z) which are not only new but also not degenerated successively by the elliptic function solutions. We believe that this method should play an important role for finding exact solutions in the mathematical physics. For these new traveling wave solutions, we give some computer simulations to illustrate our main results.
Linear Elastic Waves - Series: Cambridge Texts in Applied Mathematics (No. 26)
NASA Astrophysics Data System (ADS)
Harris, John G.
2001-10-01
Wave propagation and scattering are among the most fundamental processes that we use to comprehend the world around us. While these processes are often very complex, one way to begin to understand them is to study wave propagation in the linear approximation. This is a book describing such propagation using, as a context, the equations of elasticity. Two unifying themes are used. The first is that an understanding of plane wave interactions is fundamental to understanding more complex wave interactions. The second is that waves are best understood in an asymptotic approximation where they are free of the complications of their excitation and are governed primarily by their propagation environments. The topics covered include reflection, refraction, the propagation of interfacial waves, integral representations, radiation and diffraction, and propagation in closed and open waveguides. Linear Elastic Waves is an advanced level textbook directed at applied mathematicians, seismologists, and engineers. Aimed at beginning graduate students Includes examples and exercises Has application in a wide range of disciplines
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.
NASA Astrophysics Data System (ADS)
Junquera, Javier; Aguado-Puente, Pablo
2013-03-01
At metal-isulator interfaces, the metallic wave functions with an energy eigenvalue within the band gap decay exponentially inside the dielectric (metal-induced gap states, MIGS). These MIGS can be actually regarded as Bloch functions with an associated complex wave vector. Usually only real values of the wave vectors are discussed in text books, since infinite periodicity is assumed and, in that situation, wave functions growing exponentially in any direction would not be physically valid. However, localized wave functions with an exponential decay are indeed perfectly valid solution of the Schrodinger equation in the presence of defects, surfaces or interfaces. For this reason, properties of MIGS have been typically discussed in terms of the complex band structure of bulk materials. The probable dependence on the interface particulars has been rarely taken into account explicitly due to the difficulties to include them into the model or simulations. We aim to characterize from first-principles simulations the MIGS in realistic ferroelectric capacitors and their connection with the complex band structure of the ferroelectric material. We emphasize the influence of the real interface beyond the complex band structure of bulk materials. Financial support provided by MICINN Grant FIS2009-12721-C04-02, and by the European Union Grant No. CP-FP 228989-2 ``OxIDes''. Computer resources provided by the RES.
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Wilczynski, Bartek; Furlong, Eileen E M
2010-04-15
Development is regulated by dynamic patterns of gene expression, which are orchestrated through the action of complex gene regulatory networks (GRNs). Substantial progress has been made in modeling transcriptional regulation in recent years, including qualitative "coarse-grain" models operating at the gene level to very "fine-grain" quantitative models operating at the biophysical "transcription factor-DNA level". Recent advances in genome-wide studies have revealed an enormous increase in the size and complexity or GRNs. Even relatively simple developmental processes can involve hundreds of regulatory molecules, with extensive interconnectivity and cooperative regulation. This leads to an explosion in the number of regulatory functions, effectively impeding Boolean-based qualitative modeling approaches. At the same time, the lack of information on the biophysical properties for the majority of transcription factors within a global network restricts quantitative approaches. In this review, we explore the current challenges in moving from modeling medium scale well-characterized networks to more poorly characterized global networks. We suggest to integrate coarse- and find-grain approaches to model gene regulatory networks in cis. We focus on two very well-studied examples from Drosophila, which likely represent typical developmental regulatory modules across metazoans. Copyright (c) 2009 Elsevier Inc. All rights reserved.
Enhancing the Relationship Between Regulators and Their Profession.
Austin, Zubin
2017-01-01
Regulators face unique pressures to balance competing priorities related to patient safety, public accountability, and practitioners' expectations. Historically, the collegial model of self-regulation has been used as a tool for risk management, to recognize the importance of profession- and context-specific judgment in complex, ambiguous clinical situations. Increasingly, as public accountability concerns have grown dominant within regulatory bodies, this collegial model has shifted toward a more antagonistic relationship between the regulators and the regulated. Wilkie and Tzountzouris (2017) highlight one profession's journey toward embedding professionalism within regulatory practices and policies through application of a right-touch regulatory philosophy. Given the complexity of regulatory work, this shift required significant strategic and deliberative thinking. The challenges of facilitating this sort of cultural shift in the role of a regulator are significant, but so too are the potential gains associated with a more engaged relationship between regulators and their practitioners.
Image processing to optimize wave energy converters
NASA Astrophysics Data System (ADS)
Bailey, Kyle Marc-Anthony
The world is turning to renewable energies as a means of ensuring the planet's future and well-being. There have been a few attempts in the past to utilize wave power as a means of generating electricity through the use of Wave Energy Converters (WEC), but only recently are they becoming a focal point in the renewable energy field. Over the past few years there has been a global drive to advance the efficiency of WEC. Placing a mechanical device either onshore or offshore that captures the energy within ocean surface waves to drive a mechanical device is how wave power is produced. This paper seeks to provide a novel and innovative way to estimate ocean wave frequency through the use of image processing. This will be achieved by applying a complex modulated lapped orthogonal transform filter bank to satellite images of ocean waves. The complex modulated lapped orthogonal transform filterbank provides an equal subband decomposition of the Nyquist bounded discrete time Fourier Transform spectrum. The maximum energy of the 2D complex modulated lapped transform subband is used to determine the horizontal and vertical frequency, which subsequently can be used to determine the wave frequency in the direction of the WEC by a simple trigonometric scaling. The robustness of the proposed method is provided by the applications to simulated and real satellite images where the frequency is known.
Wave theory of turbulence in compressible media (acoustic theory of turbulence)
NASA Technical Reports Server (NTRS)
Kentzer, C. P.
1975-01-01
The generation and the transmission of sound in turbulent flows are treated as one of the several aspects of wave propagation in turbulence. Fluid fluctuations are decomposed into orthogonal Fourier components, with five interacting modes of wave propagation: two vorticity modes, one entropy mode, and two acoustic modes. Wave interactions, governed by the inhomogeneous and nonlinear terms of the perturbed Navier-Stokes equations, are modeled by random functions which give the rates of change of wave amplitudes equal to the averaged interaction terms. The statistical framework adopted is a quantum-like formulation in terms of complex distribution functions. The spatial probability distributions are given by the squares of the absolute values of the complex characteristic functions. This formulation results in nonlinear diffusion-type transport equations for the probability densities of the five modes of wave propagation.
Rogue waves in multiple-solitons-inelastic collisions — The complex Sharma-Tasso-Olver equation
NASA Astrophysics Data System (ADS)
Abdel-Gawad, H. I.; Tantawy, M.
2018-03-01
Very recently, a mechanism to the formation of rogue waves (RWs) has been proposed by the authors. In this paper, the formation of RWs in case of the complex Sharma-Tasso-Olver (STO) equation is studied. In the STO equation, one, two and three-soliton solutions are obtained. Due to the inelastic collisions, these soliton waves are fused to one. Under the free parameters constraint this behavior do occurs. The mechanism of formation of RWs is due to the collisions of solitons and multi-periodic waves (like spectral band). These RWs as giant waves, which may be very sharp or chaotic are similar to RWs in laser. The work is done here by using the generalized unified method (GUM).
Malleable machines in transcription regulation: the mediator complex.
Tóth-Petróczy, Agnes; Oldfield, Christopher J; Simon, István; Takagi, Yuichiro; Dunker, A Keith; Uversky, Vladimir N; Fuxreiter, Monika
2008-12-01
The Mediator complex provides an interface between gene-specific regulatory proteins and the general transcription machinery including RNA polymerase II (RNAP II). The complex has a modular architecture (Head, Middle, and Tail) and cryoelectron microscopy analysis suggested that it undergoes dramatic conformational changes upon interactions with activators and RNAP II. These rearrangements have been proposed to play a role in the assembly of the preinitiation complex and also to contribute to the regulatory mechanism of Mediator. In analogy to many regulatory and transcriptional proteins, we reasoned that Mediator might also utilize intrinsically disordered regions (IDRs) to facilitate structural transitions and transmit transcriptional signals. Indeed, a high prevalence of IDRs was found in various subunits of Mediator from both Saccharomyces cerevisiae and Homo sapiens, especially in the Tail and the Middle modules. The level of disorder increases from yeast to man, although in both organisms it significantly exceeds that of multiprotein complexes of a similar size. IDRs can contribute to Mediator's function in three different ways: they can individually serve as target sites for multiple partners having distinctive structures; they can act as malleable linkers connecting globular domains that impart modular functionality on the complex; and they can also facilitate assembly and disassembly of complexes in response to regulatory signals. Short segments of IDRs, termed molecular recognition features (MoRFs) distinguished by a high protein-protein interaction propensity, were identified in 16 and 19 subunits of the yeast and human Mediator, respectively. In Saccharomyces cerevisiae, the functional roles of 11 MoRFs have been experimentally verified, and those in the Med8/Med18/Med20 and Med7/Med21 complexes were structurally confirmed. Although the Saccharomyces cerevisiae and Homo sapiens Mediator sequences are only weakly conserved, the arrangements of the disordered regions and their embedded interaction sites are quite similar in the two organisms. All of these data suggest an integral role for intrinsic disorder in Mediator's function.
A Continuum Model of Actin Waves in Dictyostelium discoideum
Khamviwath, Varunyu; Hu, Jifeng; Othmer, Hans G.
2013-01-01
Actin waves are complex dynamical patterns of the dendritic network of filamentous actin in eukaryotes. We developed a model of actin waves in PTEN-deficient Dictyostelium discoideum by deriving an approximation of the dynamics of discrete actin filaments and combining it with a signaling pathway that controls filament branching. This signaling pathway, together with the actin network, contains a positive feedback loop that drives the actin waves. Our model predicts the structure, composition, and dynamics of waves that are consistent with existing experimental evidence, as well as the biochemical dependence on various protein partners. Simulation suggests that actin waves are initiated when local actin network activity, caused by an independent process, exceeds a certain threshold. Moreover, diffusion of proteins that form a positive feedback loop with the actin network alone is sufficient for propagation of actin waves at the observed speed of . Decay of the wave back can be caused by scarcity of network components, and the shape of actin waves is highly dependent on the filament disassembly rate. The model allows retraction of actin waves and captures formation of new wave fronts in broken waves. Our results demonstrate that a delicate balance between a positive feedback, filament disassembly, and local availability of network components is essential for the complex dynamics of actin waves. PMID:23741312
Modeling Water Waves with Smoothed Particle Hydrodynamics
2013-09-30
SPH Model for Water Waves and Other Free Surface Flows ...Lagrangian nature of SPH allows the modeling of wave breaking, surf zones, ship waves, and wave-structure interaction, where the free surface becomes...proving to be a competent modeling scheme for free surface flows in three dimensions including the complex flows of the surf zone. As the GPU
NASA Astrophysics Data System (ADS)
Baglivo, Fabricio Hugo; Arini, Pedro David
2011-12-01
Electrocardiographic repolarization abnormalities can be detected by Principal Components Analysis of the T-wave. In this work we studied the efect of signal averaging on the mean value and reproducibility of the ratio of the 2nd to the 1st eigenvalue of T-wave (T21W) and the absolute and relative T-wave residuum (TrelWR and TabsWR) in the ECG during ischemia induced by Percutaneous Coronary Intervention. Also, the intra-subject and inter-subject variability of T-wave parameters have been analyzed. Results showed that TrelWR and TabsWR evaluated from the average of 10 complexes had lower values and higher reproducibility than those obtained from 1 complex. On the other hand T21W calculated from 10 complexes did not show statistical diferences versus the T21W calculated on single beats. The results of this study corroborate that, with a signal averaging technique, the 2nd and the 1st eigenvalue are not afected by noise while the 4th to 8th eigenvalues are so much afected by this, suggesting the use of the signal averaged technique before calculation of absolute and relative T-wave residuum. Finally, we have shown that T-wave morphology parameters present high intra-subject stability.
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Regulatory Compliance in Multi-Tier Supplier Networks
NASA Technical Reports Server (NTRS)
Goossen, Emray R.; Buster, Duke A.
2014-01-01
Over the years, avionics systems have increased in complexity to the point where 1st tier suppliers to an aircraft OEM find it financially beneficial to outsource designs of subsystems to 2nd tier and at times to 3rd tier suppliers. Combined with challenging schedule and budgetary pressures, the environment in which safety-critical systems are being developed introduces new hurdles for regulatory agencies and industry. This new environment of both complex systems and tiered development has raised concerns in the ability of the designers to ensure safety considerations are fully addressed throughout the tier levels. This has also raised questions about the sufficiency of current regulatory guidance to ensure: proper flow down of safety awareness, avionics application understanding at the lower tiers, OEM and 1st tier oversight practices, and capabilities of lower tier suppliers. Therefore, NASA established a research project to address Regulatory Compliance in a Multi-tier Supplier Network. This research was divided into three major study efforts: 1. Describe Modern Multi-tier Avionics Development 2. Identify Current Issues in Achieving Safety and Regulatory Compliance 3. Short-term/Long-term Recommendations Toward Higher Assurance Confidence This report presents our findings of the risks, weaknesses, and our recommendations. It also includes a collection of industry-identified risks, an assessment of guideline weaknesses related to multi-tier development of complex avionics systems, and a postulation of potential modifications to guidelines to close the identified risks and weaknesses.
From N-WASP to WAVE: key molecules for regulation of cortical actin organization.
Takenawa, Tadaomi
2005-01-01
We first isolated N-WASP as one of the proteins bound to Ash/Grb2 SH3 domain. This protein has a VCA region (verplorin-like, cofilin-like, acidic region) at the C-terminus, which binds to G-actin and Arp2/3 complex, and several functional domains at the N-terminus, such as WHD (WASP homology domain) and GBD/CRIB domain. N-WASP activates Arp2/3 complex-dependent actin polymerization through the VCA region, leading to filopodium formation. Next, we found WAVE1, WAVE2 and WAVE3. All these proteins have also VCA regions at C-terminal areas and induce membrane ruffle formation. To clarify the different roles of WAVE1 and WAVE2, we established WAVE1- and WAVE2-deficient mouse embryonic fibroblasts (MEFs), because these two WAVEs are expressed in MEF. When wild-type MEFs are stimulated randomly by PDGF, two types of ruffles, peripheral and dorsal, are formed. However, dorsal ruffle formation does not occurin WAVE1-deficient MEFs. In contrast, peripheral ruffle formation is diminished in WAVE2-deficient MEFs. On the other hand, in MEFs migrating towards a chemoattractant gradient, only peripheral ruffles (lamellipodia) are formed. In this migration, WAVE1-deficient MEFs still could form lamellipodia but WAVE2-deficient MEFs could not. All these data show that WAVE2 but not WAVE1 is essential for lamellipodium formation and directed migration.
Albert, Nick W.; Davies, Kevin M.; Lewis, David H.; Zhang, Huaibi; Montefiori, Mirco; Brendolise, Cyril; Boase, Murray R.; Ngo, Hanh; Jameson, Paula E.; Schwinn, Kathy E.
2014-01-01
Plants require sophisticated regulatory mechanisms to ensure the degree of anthocyanin pigmentation is appropriate to myriad developmental and environmental signals. Central to this process are the activity of MYB-bHLH-WD repeat (MBW) complexes that regulate the transcription of anthocyanin genes. In this study, the gene regulatory network that regulates anthocyanin synthesis in petunia (Petunia hybrida) has been characterized. Genetic and molecular evidence show that the R2R3-MYB, MYB27, is an anthocyanin repressor that functions as part of the MBW complex and represses transcription through its C-terminal EAR motif. MYB27 targets both the anthocyanin pathway genes and basic-helix-loop-helix (bHLH) ANTHOCYANIN1 (AN1), itself an essential component of the MBW activation complex for pigmentation. Other features of the regulatory network identified include inhibition of AN1 activity by the competitive R3-MYB repressor MYBx and the activation of AN1, MYB27, and MYBx by the MBW activation complex, providing for both reinforcement and feedback regulation. We also demonstrate the intercellular movement of the WDR protein (AN11) and R3-repressor (MYBx), which may facilitate anthocyanin pigment pattern formation. The fundamental features of this regulatory network in the Asterid model of petunia are similar to those in the Rosid model of Arabidopsis thaliana and are thus likely to be widespread in the Eudicots. PMID:24642943
Kheir, Wassim Abou; Gevrey, Jean-Claude; Yamaguchi, Hideki; Isaac, Beth; Cox, Dianne
2005-11-15
Colony-stimulating factor 1 (CSF-1) is an important physiological chemoattractant for macrophages. The mechanisms by which CSF-1 elicits the formation of filamentous actin (F-actin)-rich membrane protrusions and induces macrophage migration are not fully understood. In particular, very little is known regarding the contribution of the different members of the Wiskott-Aldrich Syndrome protein (WASP) family of actin regulators in response to CSF-1. Although a role for WASP itself in macrophage chemotaxis has been previously identified, no data was available regarding the function of WASP family verprolin-homologous (WAVE) proteins in this cell type. We found that WAVE2 was the predominant isoform to be expressed in primary macrophages and in cells derived from the murine monocyte/macrophage RAW264.7 cell line (RAW/LR5). CSF-1 treatment of macrophages resulted in WAVE2 accumulation in F-actin-rich protrusions induced by CSF-1. Inhibition of WAVE2 function by expressing a dominant-negative mutant or introducing anti-WAVE2 antibodies in RAW/LR5 cells, as well as reduction of endogenous WAVE2 expression by RNA-mediated interference (RNAi), resulted in a significant reduction of CSF-1-elicited F-actin protrusions. WAVE2 was found in a protein complex together with Abelson kinase interactor 1 (Abi1) in resting or stimulated cells. Both WAVE2 and Abi1 were recruited to and necessary for the formation of F-actin protrusions in response to CSF-1. Reducing the levels of WAVE2, directly or by targeting Abi1, resulted in an impaired cell migration to CSF-1. Altogether these data identify a WAVE2-Abi1 complex crucial for the normal actin cytoskeleton reorganization and migration of macrophages in response to CSF-1.
NASA Astrophysics Data System (ADS)
Verisokin, Andrey Yu.; Postnov, Dmitry E.; Verveyko, Darya V.; Brazhe, Alexey R.
2018-04-01
The most abundant non-neuronal cells in the brain, astrocytes, populate all parts of the central nervous system (CNS). Astrocytic calcium activity ranging from subcellular sparkles to intercellular waves is believed to be the key to a plethora of regulatory pathways in the central nervous system from synaptic plasticity to blood flow regulation. Modeling of the calcium wave initiation and transmission and their spatiotemporal dynamics is therefore an important step stone in understanding the crucial cogs of cognition. Astrocytes are active sensors of ongoing neuronal and synaptic activity, and neurotransmitters diffusing from the synaptic cleft make a strong impact on the astrocytic activity. Here we propose a model describing the patterns of calcium wave formation at a single cell level and discuss the interplay between astrocyte shape the calcium waves dynamics driven by local stochastic surges of glutamate simulating synaptic activity.
Nikolić, Miloš; Papantonis, Argyris
2017-01-01
Abstract Genome-wide association studies (GWAS) have emerged as a powerful tool to uncover the genetic basis of human common diseases, which often show a complex, polygenic and multi-factorial aetiology. These studies have revealed that 70–90% of all single nucleotide polymorphisms (SNPs) associated with common complex diseases do not occur within genes (i.e. they are non-coding), making the discovery of disease-causative genetic variants and the elucidation of the underlying pathological mechanisms far from straightforward. Based on emerging evidences suggesting that disease-associated SNPs are frequently found within cell type-specific regulatory sequences, here we present GARLIC (GWAS-based Prediction Toolkit for Connecting Diseases and Cell Types), a user-friendly, multi-purpose software with an associated database and online viewer that, using global maps of cis-regulatory elements, can aetiologically connect human diseases with relevant cell types. Additionally, GARLIC can be used to retrieve potential disease-causative genetic variants overlapping regulatory sequences of interest. Overall, GARLIC can satisfy several important needs within the field of medical genetics, thus potentially assisting in the ultimate goal of uncovering the elusive and complex genetic basis of common human disorders. PMID:28007912
18 CFR 367.9210 - Account 921, Office supplies and expenses.
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2010-04-01
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78 FR 70588 - STP Nuclear Operating Company; South Texas Project
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2013-11-26
... efficiency; (8) wind power; (9) solar power; (10) hydroelectric power; (11) ocean wave and current energy... generic environmental impact statement for license renewal of nuclear plants; issuance. SUMMARY: Notice is hereby given that the U.S. Nuclear Regulatory Commission (NRC) has published the final, plant-specific...
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...) solar power; (9) wind power; (10) biomass waste; (11) hydroelectric power; (12) ocean wave and current... Nuclear Plants AGENCY: Nuclear Regulatory Commission. ACTION: Final Supplement 47 to the Generic Environmental Impact Statement for License Renewal of Nuclear Plants; issuance. SUMMARY: Notice is hereby given...
MODELING WAVE-INDUCED ENTRAINMENT OF MUD IN NEWNANS LAKE, FLORIDA
Many shallow lakes in the southeastern US are eutrophic, and as such, the water quality in these lakes is of concern to state and federal environmental regulatory agencies. Some of these lakes have been classified as impaired with one or more nutrients being the stressor. For the...
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Almendros, J.; Chouet, B.; Dawson, P.; Huber, Caleb G.
2002-01-01
Seismic antennas constitute a powerful tool for the analysis of complex wave fields. Well-designed antennas can identify and separate components of a complex wave field based on their distinct propagation properties. The combination of several antennas provides the basis for a more complete understanding of volcanic wave fields, including an estimate of the location of each individual wave-field component identified simultaneously by at least two antennas. We used frequency-slowness analyses of data from three antennas to identify and locate the different components contributing to the wave fields recorded at Kilauea volcano, Hawaii, in February 1997. The wave-field components identified are (1) a sustained background volcanic tremor in the form of body waves generated in a shallow hydrothermal system located below the northeastern edge of the Halemaumau pit crater; (2) surface waves generated along the path between this hydrothermal source and the antennas; (3) back-scattered surface wave energy from a shallow reflector located near the southeastern rim of Kilauea caldera; (4) evidence for diffracted wave components originating at the southeastern edge of Halemaumau; and (5) body waves reflecting the activation of a deeper tremor source between 02 hr 00 min and 16 hr 00 min Hawaii Standard Time on 11 February.
Full-wave generalizations of the fundamental Gaussian beam.
Seshadri, S R
2009-12-01
The basic full wave corresponding to the fundamental Gaussian beam was discovered for the outwardly propagating wave in a half-space by the introduction of a source in the complex space. There is a class of extended full waves all of which reduce to the same fundamental Gaussian beam in the appropriate limit. For the extended full Gaussian waves that include the basic full Gaussian wave as a special case, the sources are in the complex space on different planes transverse to the propagation direction. The sources are cylindrically symmetric Gaussian distributions centered at the origin of the transverse planes, the axis of symmetry being the propagation direction. For the special case of the basic full Gaussian wave, the source is a point source. The radiation intensity of the extended full Gaussian waves is determined and their characteristics are discussed and compared with those of the fundamental Gaussian beam. The extended full Gaussian waves are also obtained for the oppositely propagating outwardly directed waves in the second half-space. The radiation intensity distributions in the two half-spaces have reflection symmetry about the midplane. The radiation intensity distributions of the various extended full Gaussian waves are not significantly different. The power carried by the extended full Gaussian waves is evaluated and compared with that of the fundamental Gaussian beam.
NASA Technical Reports Server (NTRS)
Brosh, A.; Kussoy, M. I.
1983-01-01
An experimental study of the flow caused by a planar shock wave impinging obliquely on a cylinder is presented. The complex three dimensional shock wave and boundary layer interaction occurring in practical problems, such as the shock wave impingement from the shuttle nose on an external fuel tank, and store carriage interference on a supersonic tactical aircraft were investigated. A data base for numerical computations of complex flows was also investigated. The experimental techniques included pressure measurements and oil flow patterns on the surface of the cylinder, and shadowgraphs and total and static pressure surveys on the leeward and windward planes of symmetry. The complete data is presented in tabular form. The results reveal a highly complex flow field with two separation zones, regions of high crossflow, and multiple reflected shocks and expansion fans.
Dynamical mechanism of atrial fibrillation: A topological approach
NASA Astrophysics Data System (ADS)
Marcotte, Christopher D.; Grigoriev, Roman O.
2017-09-01
While spiral wave breakup has been implicated in the emergence of atrial fibrillation, its role in maintaining this complex type of cardiac arrhythmia is less clear. We used the Karma model of cardiac excitation to investigate the dynamical mechanisms that sustain atrial fibrillation once it has been established. The results of our numerical study show that spatiotemporally chaotic dynamics in this regime can be described as a dynamical equilibrium between topologically distinct types of transitions that increase or decrease the number of wavelets, in general agreement with the multiple wavelets' hypothesis. Surprisingly, we found that the process of continuous excitation waves breaking up into discontinuous pieces plays no role whatsoever in maintaining spatiotemporal complexity. Instead, this complexity is maintained as a dynamical balance between wave coalescence—a unique, previously unidentified, topological process that increases the number of wavelets—and wave collapse—a different topological process that decreases their number.
Advancing a Vision for Regulatory Science Training
Adamo, Joan E.; Wilhelm, Erin E.
2015-01-01
Abstract Regulatory science, a complex field which draws on science, law, and policy, is a growing discipline in medical‐related applications. Competencies help define both a discipline and the criteria to measure high‐quality learning experiences. This paper identifies competencies for regulatory science, how they were developed, and broader recommendations to enhance education and training in this burgeoning field, including a multifaceted training approach. PMID:26083660
Bounded Error Schemes for the Wave Equation on Complex Domains
NASA Technical Reports Server (NTRS)
Abarbanel, Saul; Ditkowski, Adi; Yefet, Amir
1998-01-01
This paper considers the application of the method of boundary penalty terms ("SAT") to the numerical solution of the wave equation on complex shapes with Dirichlet boundary conditions. A theory is developed, in a semi-discrete setting, that allows the use of a Cartesian grid on complex geometries, yet maintains the order of accuracy with only a linear temporal error-bound. A numerical example, involving the solution of Maxwell's equations inside a 2-D circular wave-guide demonstrates the efficacy of this method in comparison to others (e.g. the staggered Yee scheme) - we achieve a decrease of two orders of magnitude in the level of the L2-error.
Transcriptional Regulatory Network Analysis of MYB Transcription Factor Family Genes in Rice.
Smita, Shuchi; Katiyar, Amit; Chinnusamy, Viswanathan; Pandey, Dev M; Bansal, Kailash C
2015-01-01
MYB transcription factor (TF) is one of the largest TF families and regulates defense responses to various stresses, hormone signaling as well as many metabolic and developmental processes in plants. Understanding these regulatory hierarchies of gene expression networks in response to developmental and environmental cues is a major challenge due to the complex interactions between the genetic elements. Correlation analyses are useful to unravel co-regulated gene pairs governing biological process as well as identification of new candidate hub genes in response to these complex processes. High throughput expression profiling data are highly useful for construction of co-expression networks. In the present study, we utilized transcriptome data for comprehensive regulatory network studies of MYB TFs by "top-down" and "guide-gene" approaches. More than 50% of OsMYBs were strongly correlated under 50 experimental conditions with 51 hub genes via "top-down" approach. Further, clusters were identified using Markov Clustering (MCL). To maximize the clustering performance, parameter evaluation of the MCL inflation score (I) was performed in terms of enriched GO categories by measuring F-score. Comparison of co-expressed cluster and clads analyzed from phylogenetic analysis signifies their evolutionarily conserved co-regulatory role. We utilized compendium of known interaction and biological role with Gene Ontology enrichment analysis to hypothesize function of coexpressed OsMYBs. In the other part, the transcriptional regulatory network analysis by "guide-gene" approach revealed 40 putative targets of 26 OsMYB TF hubs with high correlation value utilizing 815 microarray data. The putative targets with MYB-binding cis-elements enrichment in their promoter region, functional co-occurrence as well as nuclear localization supports our finding. Specially, enrichment of MYB binding regions involved in drought-inducibility implying their regulatory role in drought response in rice. Thus, the co-regulatory network analysis facilitated the identification of complex OsMYB regulatory networks, and candidate target regulon genes of selected guide MYB genes. The results contribute to the candidate gene screening, and experimentally testable hypotheses for potential regulatory MYB TFs, and their targets under stress conditions.
2012-03-09
equation is a product of a complex basis vector in Jackson and a linear combination of plane wave functions. We convert both the amplitudes and the...wave function arguments from complex scalars to complex vectors . This conversion allows us to separate the electric field vector and the imaginary...magnetic field vector , because exponentials of imaginary scalars convert vectors to imaginary vectors and vice versa, while ex- ponentials of imaginary
Methylphenidate blocks effort-induced depletion of regulatory control in healthy volunteers.
Sripada, Chandra; Kessler, Daniel; Jonides, John
2014-06-01
A recent wave of studies--more than 100 conducted over the last decade--has shown that exerting effort at controlling impulses or behavioral tendencies leaves a person depleted and less able to engage in subsequent rounds of regulation. Regulatory depletion is thought to play an important role in everyday problems (e.g., excessive spending, overeating) as well as psychiatric conditions, but its neurophysiological basis is poorly understood. Using a placebo-controlled, double-blind design, we demonstrated that the psychostimulant methylphenidate (commonly known as Ritalin), a catecholamine reuptake blocker that increases dopamine and norepinephrine at the synaptic cleft, fully blocks effort-induced depletion of regulatory control. Spectral analysis of trial-by-trial reaction times revealed specificity of methylphenidate effects on regulatory depletion in the slow-4 frequency band. This band is associated with the operation of resting-state brain networks that produce mind wandering, which raises potential connections between our results and recent brain-network-based models of control over attention. © The Author(s) 2014.
Laarits, T; Bordalo, P; Lemos, B
2016-08-01
Regulatory networks play a central role in the modulation of gene expression, the control of cellular differentiation, and the emergence of complex phenotypes. Regulatory networks could constrain or facilitate evolutionary adaptation in gene expression levels. Here, we model the adaptation of regulatory networks and gene expression levels to a shift in the environment that alters the optimal expression level of a single gene. Our analyses show signatures of natural selection on regulatory networks that both constrain and facilitate rapid evolution of gene expression level towards new optima. The analyses are interpreted from the standpoint of neutral expectations and illustrate the challenge to making inferences about network adaptation. Furthermore, we examine the consequence of variable stabilizing selection across genes on the strength and direction of interactions in regulatory networks and in their subsequent adaptation. We observe that directional selection on a highly constrained gene previously under strong stabilizing selection was more efficient when the gene was embedded within a network of partners under relaxed stabilizing selection pressure. The observation leads to the expectation that evolutionarily resilient regulatory networks will contain optimal ratios of genes whose expression is under weak and strong stabilizing selection. Altogether, our results suggest that the variable strengths of stabilizing selection across genes within regulatory networks might itself contribute to the long-term adaptation of complex phenotypes. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.
Martínez-Núñez, Mario Alberto; Poot-Hernandez, Augusto Cesar; Rodríguez-Vázquez, Katya; Perez-Rueda, Ernesto
2013-01-01
In this work, the content of enzymes and DNA-binding transcription factors (TFs) in 794 non-redundant prokaryotic genomes was evaluated. The identification of enzymes was based on annotations deposited in the KEGG database as well as in databases of functional domains (COG and PFAM) and structural domains (Superfamily). For identifications of the TFs, hidden Markov profiles were constructed based on well-known transcriptional regulatory families. From these analyses, we obtained diverse and interesting results, such as the negative rate of incremental changes in the number of detected enzymes with respect to the genome size. On the contrary, for TFs the rate incremented as the complexity of genome increased. This inverse related performance shapes the diversity of metabolic and regulatory networks and impacts the availability of enzymes and TFs. Furthermore, the intersection of the derivatives between enzymes and TFs was identified at 9,659 genes, after this point, the regulatory complexity grows faster than metabolic complexity. In addition, TFs have a low number of duplications, in contrast to the apparent high number of duplications associated with enzymes. Despite the greater number of duplicated enzymes versus TFs, the increment by which duplicates appear is higher in TFs. A lower proportion of enzymes among archaeal genomes (22%) than in the bacterial ones (27%) was also found. This low proportion might be compensated by the interconnection between the metabolic pathways in Archaea. A similar proportion was also found for the archaeal TFs, for which the formation of regulatory complexes has been proposed. Finally, an enrichment of multifunctional enzymes in Bacteria, as a mechanism of ecological adaptation, was detected.
Martínez-Núñez, Mario Alberto; Poot-Hernandez, Augusto Cesar; Rodríguez-Vázquez, Katya; Perez-Rueda, Ernesto
2013-01-01
In this work, the content of enzymes and DNA-binding transcription factors (TFs) in 794 non-redundant prokaryotic genomes was evaluated. The identification of enzymes was based on annotations deposited in the KEGG database as well as in databases of functional domains (COG and PFAM) and structural domains (Superfamily). For identifications of the TFs, hidden Markov profiles were constructed based on well-known transcriptional regulatory families. From these analyses, we obtained diverse and interesting results, such as the negative rate of incremental changes in the number of detected enzymes with respect to the genome size. On the contrary, for TFs the rate incremented as the complexity of genome increased. This inverse related performance shapes the diversity of metabolic and regulatory networks and impacts the availability of enzymes and TFs. Furthermore, the intersection of the derivatives between enzymes and TFs was identified at 9,659 genes, after this point, the regulatory complexity grows faster than metabolic complexity. In addition, TFs have a low number of duplications, in contrast to the apparent high number of duplications associated with enzymes. Despite the greater number of duplicated enzymes versus TFs, the increment by which duplicates appear is higher in TFs. A lower proportion of enzymes among archaeal genomes (22%) than in the bacterial ones (27%) was also found. This low proportion might be compensated by the interconnection between the metabolic pathways in Archaea. A similar proportion was also found for the archaeal TFs, for which the formation of regulatory complexes has been proposed. Finally, an enrichment of multifunctional enzymes in Bacteria, as a mechanism of ecological adaptation, was detected. PMID:23922780
Kursawe, Michael A; Zimmer, Hubert D
2015-06-01
We investigated the impact of perceptual processing demands on visual working memory of coloured complex random polygons during change detection. Processing load was assessed by pupil size (Exp. 1) and additionally slow wave potentials (Exp. 2). Task difficulty was manipulated by presenting different set sizes (1, 2, 4 items) and by making different features (colour, shape, or both) task-relevant. Memory performance in the colour condition was better than in the shape and both condition which did not differ. Pupil dilation and the posterior N1 increased with set size independent of type of feature. In contrast, slow waves and a posterior P2 component showed set size effects but only if shape was task-relevant. In the colour condition slow waves did not vary with set size. We suggest that pupil size and N1 indicates different states of attentional effort corresponding to the number of presented items. In contrast, slow waves reflect processes related to encoding and maintenance strategies. The observation that their potentials vary with the type of feature (simple colour versus complex shape) indicates that perceptual complexity already influences encoding and storage and not only comparison of targets with memory entries at the moment of testing. Copyright © 2015 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Khalili, Ashkan; Jha, Ratneshwar; Samaratunga, Dulip
2016-11-01
Wave propagation analysis in 2-D composite structures is performed efficiently and accurately through the formulation of a User-Defined Element (UEL) based on the wavelet spectral finite element (WSFE) method. The WSFE method is based on the first-order shear deformation theory which yields accurate results for wave motion at high frequencies. The 2-D WSFE model is highly efficient computationally and provides a direct relationship between system input and output in the frequency domain. The UEL is formulated and implemented in Abaqus (commercial finite element software) for wave propagation analysis in 2-D composite structures with complexities. Frequency domain formulation of WSFE leads to complex valued parameters, which are decoupled into real and imaginary parts and presented to Abaqus as real values. The final solution is obtained by forming a complex value using the real number solutions given by Abaqus. Five numerical examples are presented in this article, namely undamaged plate, impacted plate, plate with ply drop, folded plate and plate with stiffener. Wave motions predicted by the developed UEL correlate very well with Abaqus simulations. The results also show that the UEL largely retains computational efficiency of the WSFE method and extends its ability to model complex features.
NASA Astrophysics Data System (ADS)
Liu, Lei; Tian, Bo; Wu, Xiao-Yu; Sun, Yan
2018-02-01
Under investigation in this paper is the higher-order rogue wave-like solutions for a nonautonomous nonlinear Schrödinger equation with external potentials which can be applied in the nonlinear optics, hydrodynamics, plasma physics and Bose-Einstein condensation. Based on the Kadomtsev-Petviashvili hierarchy reduction, we construct the Nth order rogue wave-like solutions in terms of the Gramian under the integrable constraint. With the help of the analytic and graphic analysis, we exhibit the first-, second- and third-order rogue wave-like solutions through the different dispersion, nonlinearity and linear potential coefficients. We find that only if the dispersion and nonlinearity coefficients are proportional to each other, heights of the background of those rogue waves maintain unchanged with time increasing. Due to the existence of complex parameters, such nonautonomous rogue waves in the higher-order cases have more complex features than those in the lower.
Ultrasonic guided waves in eccentric annular pipes
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pattanayak, Roson Kumar; Balasubramaniam, Krishnan; Rajagopal, Prabhu
2014-02-18
This paper studies the feasibility of using ultrasonic guided waves to rapidly inspect tubes and pipes for possible eccentricity. While guided waves are well established in the long range inspection of structures such as pipes and plates, studies for more complex cross sections are limited and analytical solutions are often difficult to obtain. Recent developments have made the Semi Analytical Finite Element (SAFE) method widely accessible for researchers to study guided wave properties in complex structures. Here the SAFE method is used to study the effect of eccentricity on the modal structures and velocities of lower order guided wave modesmore » in thin pipes of diameters typically of interest to the industry. Results are validated using experiments. The paper demonstrates that even a small eccentricity in the pipe can strongly affect guided wave mode structures and velocities and hence shows potential for pipe eccentricity inspection.« less
NASA Astrophysics Data System (ADS)
Lee, Myoung-Jae; Jung, Young-Dae
2017-03-01
The influence of electron-ion collision frequency and dust charge on the growth rate of two-stream instability of the electrostatic surface wave propagating at the interface of semi-infinite complex plasma whose constituents are electrons, negatively charged dust, and streaming ions. It is found that the surface wave can be unstable if the multiplication of wave number and ion flow velocity is greater than the total plasma frequency of electrons and dusts. The analytical solution of the growth rate is derived as a function of collision frequency, dust charge, and ion-to-electron density ratio. It is found that the growth rate is inversely proportional to the collision rate, but it is enhanced as the number of electrons residing on the dust grain surface is increased. The growth rate of surface wave is compared to that of the bulk wave.
Near-field plasmonic beam engineering with complex amplitude modulation based on metasurface
NASA Astrophysics Data System (ADS)
Song, Xu; Huang, Lingling; Sun, Lin; Zhang, Xiaomeng; Zhao, Ruizhe; Li, Xiaowei; Wang, Jia; Bai, Benfeng; Wang, Yongtian
2018-02-01
Metasurfaces have recently intrigued extensive interest due to their ability to locally manipulate electromagnetic waves, which provide great feasibility for tailoring both propagation waves and surface plasmon polaritons (SPPs). Manipulation of SPPs with arbitrary complex fields is an important issue in integrated nanophotonics due to their capability of guiding waves with subwavelength footprints. Here, an approach with metasurfaces composed of nanoaperture arrays is proposed and experimentally demonstrated which can effectively manipulate the complex amplitude of SPPs in the near-field regime. Tailoring the azimuthal angles of individual nanoapertures and simultaneously tuning their geometric parameters, the phase and amplitude are controlled based on the Pancharatnam-Berry phases and their individual transmission coefficients. For the verification of the concept, Airy plasmons and axisymmetric Airy-SPPs are generated. The results of numerical simulations and near-field imaging are consistent with each other. Besides the rigorous simulations, we applied a 2D dipole analysis for additional analysis. This strategy of complex amplitude manipulation with metasurfaces can be used for potential applications in plasmonic beam shaping, integrated optoelectronic systems, and surface wave holography.
New micro waveforms firstly recorded on electrocardiogram in human.
Liu, Renguang; Chang, Qinghua; Chen, Juan
2015-10-01
In our study, not only the P-QRS-T waves but also the micro-wavelets before QRS complex (in P wave and PR segment) and after QRS complex (ST segment and upstroke of T wave) were first to be identified on surface electrocardiogram in human by the "new electrocardiogram" machine (model PHS-A10) according to conventional 12-lead electrocardiogram connection methods. By comparison to the conventional electrocardiogram in 100 cases of healthy individuals and several patients with arrhythmias, we have found that the wavelets before P wave theoretically reflected electrical activity of sinus node and the micro-wavelets before QRS complex may be related to atrioventricular conduction system (atrioventricular node, His bundle and bundle branch) potentials. Noninvasive atrioventricular node and His bundle potential tracing will contribute to differentiation of the origin of wide QRS and the location of the atrioventricular block. We also have found that the wavelets after QRS complex may be associated with phase 2 and 3 repolarization of ventricular action potential, which will further reveal ventricular repolarization changes. Copyright © 2015 Elsevier Ltd. All rights reserved.
Power distribution in complex environmental negotiations: Does balance matter?
Burkardt, N.; Lamb, B.L.; Taylor, J.G.
1997-01-01
We studied six interagency negotiations covering Federal Energy Regulatory Commission (FERC) hydroelectric power licenses. Negotiations occurred between state and federal resource agencies and developers over project operations and natural resource mitigation. We postulated that a balance of power among parties was necessary for successful negotiations. We found a complex relationship between balanced power and success and conclude that a balance of power was associated with success in these negotiations. Power played a dynamic role in the bargaining and illuminates important considerations for regulatory design.
Federal Register 2010, 2011, 2012, 2013, 2014
2012-06-14
.../taker fees and rebates, which are designed to attract complex orders to the Exchange, and has a specific... per contract applicable to customers that transact in complex orders, i.e., customer complex orders that interact with complex orders residing on the complex order book thereby taking liquidity from the...
Xing, Na; Ji, Lizhen; Song, Jie; Ma, Jingchun; Li, Shangge; Ren, Zongming; Xu, Fei; Zhu, Jianping
2017-10-01
The electrocardiogram (ECG) of zebra fish (Danio rerio) expresses cardiac features that are similar to humans. Here we use sharp microelectrode measurements to obtain ECG characteristics in adult zebra fish and analyze the effects of cadmium chloride (CdCl 2 ) on the heart. We observe the overall changes of ECG parameters in different treatments (0.1 TU, 0.5 TU and 1.0 TU CdCl 2 ), including P wave, Q wave, R wave, S wave, T wave, PR interval (atrial contraction), QRS complex (ventricular depolarization), ST segment, and QT interval (ventricular repolarization). The trends of the ECG parameters showed some responses to the concentration and exposure time of CdCl 2 , but it was difficult to obtain more information about the useful indicators in water quality assessment depending on tendency analysis alone. A self-organizing map (SOM) showed that P values, R values, and T values were similar; R wave and T wave amplitude were similar; and most important, QRS value was similar to the CdCl 2 stress according to the classified data patterns including CdCl 2 stress (E) and ECG components based on the Ward linkage. It suggested that the duration of QRS complex was related to environmental stress E directly. The specification and evaluation of ECG parameters in Cd 2+ pollution suggested that there is a markedly significant correlation between QRS complex and CdCl 2 stress with the highest r (0.729) and the smallest p (0.002) among all ECG characteristics. In this case, it is concluded that QRS complex can be used as an indicator in the CdCl 2 stress assessment due to the lowest AIC data abased on the linear regression model between the CdCl 2 stress and ECG parameters. Copyright © 2017 Elsevier B.V. All rights reserved.
Electrogram fractionation in murine HL-1 atrial monolayer model.
Umapathy, Karthikeyan; Masse, Stephane; Kolodziejska, Karolina; Veenhuyzen, George D; Chauhan, Vijay S; Husain, Mansoor; Farid, Talha; Downar, Eugene; Sevaptsidis, Elias; Nanthakumar, Kumaraswamy
2008-07-01
Complex fractionated atrial electrograms have been suggested as important targets for catheter ablation of atrial fibrillation. The etiology and the mechanism of these signals have not been completely elucidated because of limitations of interpretation of these signals in relation to simultaneously acquired signals in the neighboring atrial tissue. This study sought to study the origin of electrogram fractionation under the conditions of rotor formation and wave fragmentation, using atrial monolayer preparations. We performed optical mapping of 45 atrial monolayer preparations using a complementary metal oxide semiconductor (CMOS) Brainvision Ultima camera system (SciMedia-Brainvision, Tokyo, Japan). We observed stable rotors in 32 of the 45 recordings. The derived bipolar electrograms did not show complex fractionation at the core of the rotor in any of the 32 recordings. We were also able to show that 2 bipolar electrodes placed adjacent to the core of a stable rotor in a zone where there is no wave break will record electrical activity for the majority of the rotor's cycle length. In 13 of the 45 recordings, wave break or wave collision events were present. Of these, 8 of 13 recordings showed complex fractionation. In 19 of the 27, simulation of meandering rotors also showed complex fractionation. Complex fractionated electrograms can be recorded at sites of migrating rotors and wave break. No fractionation occurs at the core of a stable rotor. Electrograms that span the rotor cycle length and alternate between 2 bipoles that straddle the core can identify site of a stable rotor.
Fundamental formulae for wave-energy conversion
Falnes, Johannes; Kurniawan, Adi
2015-01-01
The time-average wave power that is absorbed from an incident wave by means of a wave-energy conversion (WEC) unit, or by an array of WEC units—i.e. oscillating immersed bodies and/or oscillating water columns (OWCs)—may be mathematically expressed in terms of the WEC units' complex oscillation amplitudes, or in terms of the generated outgoing (diffracted plus radiated) waves, or alternatively, in terms of the radiated waves alone. Following recent controversy, the corresponding three optional expressions are derived, compared and discussed in this paper. They all provide the correct time-average absorbed power. However, only the first-mentioned expression is applicable to quantify the instantaneous absorbed wave power and the associated reactive power. In this connection, new formulae are derived that relate the ‘added-mass’ matrix, as well as a couple of additional reactive radiation-parameter matrices, to the difference between kinetic energy and potential energy in the water surrounding the immersed oscillating WEC array. Further, a complex collective oscillation amplitude is introduced, which makes it possible to derive, by a very simple algebraic method, various simple expressions for the maximum time-average wave power that may be absorbed by the WEC array. The real-valued time-average absorbed power is illustrated as an axisymmetric paraboloid defined on the complex collective-amplitude plane. This is a simple illustration of the so-called ‘fundamental theorem for wave power’. Finally, the paper also presents a new derivation that extends a recently published result on the direction-average maximum absorbed wave power to cases where the WEC array's radiation damping matrix may be singular and where the WEC array may contain OWCs in addition to oscillating bodies. PMID:26064612
Fundamental formulae for wave-energy conversion.
Falnes, Johannes; Kurniawan, Adi
2015-03-01
The time-average wave power that is absorbed from an incident wave by means of a wave-energy conversion (WEC) unit, or by an array of WEC units-i.e. oscillating immersed bodies and/or oscillating water columns (OWCs)-may be mathematically expressed in terms of the WEC units' complex oscillation amplitudes, or in terms of the generated outgoing (diffracted plus radiated) waves, or alternatively, in terms of the radiated waves alone. Following recent controversy, the corresponding three optional expressions are derived, compared and discussed in this paper. They all provide the correct time-average absorbed power. However, only the first-mentioned expression is applicable to quantify the instantaneous absorbed wave power and the associated reactive power. In this connection, new formulae are derived that relate the 'added-mass' matrix, as well as a couple of additional reactive radiation-parameter matrices, to the difference between kinetic energy and potential energy in the water surrounding the immersed oscillating WEC array. Further, a complex collective oscillation amplitude is introduced, which makes it possible to derive, by a very simple algebraic method, various simple expressions for the maximum time-average wave power that may be absorbed by the WEC array. The real-valued time-average absorbed power is illustrated as an axisymmetric paraboloid defined on the complex collective-amplitude plane. This is a simple illustration of the so-called 'fundamental theorem for wave power'. Finally, the paper also presents a new derivation that extends a recently published result on the direction-average maximum absorbed wave power to cases where the WEC array's radiation damping matrix may be singular and where the WEC array may contain OWCs in addition to oscillating bodies.
Conversion of evanescent Lamb waves into propagating waves via a narrow aperture edge.
Yan, Xiang; Yuan, Fuh-Gwo
2015-06-01
This paper presents a quantitative study of conversion of evanescent Lamb waves into propagating in isotropic plates. The conversion is substantiated by prescribing time-harmonic Lamb displacements/tractions through a narrow aperture at an edge of a semi-infinite plate. Complex-valued dispersion and group velocity curves are employed to characterize the conversion process. The amplitude coefficient of the propagating Lamb modes converted from evanescent is quantified based on the complex reciprocity theorem via a finite element analysis. The power flow generated into the plate can be separated into radiative and reactive parts made on the basis of propagating and evanescent Lamb waves, where propagating Lamb waves are theoretically proved to radiate pure real power flow, and evanescent Lamb waves carry reactive pure imaginary power flow. The propagating power conversion efficiency is then defined to quantitatively describe the conversion. The conversion efficiency is strongly frequency dependent and can be significant. With the converted propagating waves from evanescent, sensors at far-field can recapture some localized damage information that is generally possessed in evanescent waves and may have potential application in structural health monitoring.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Anderson, Dale N; Bonner, Jessie L; Stroujkova, Anastasia
Our objective is to improve seismic event screening using the properties of surface waves, We are accomplishing this through (1) the development of a Love-wave magnitude formula that is complementary to the Russell (2006) formula for Rayleigh waves and (2) quantifying differences in complexities and magnitude variances for earthquake and explosion-generated surface waves. We have applied the M{sub s} (VMAX) analysis (Bonner et al., 2006) using both Love and Rayleigh waves to events in the Middle East and Korean Peninsula, For the Middle East dataset consisting of approximately 100 events, the Love M{sub s} (VMAX) is greater than the Rayleighmore » M{sub s} (VMAX) estimated for individual stations for the majority of the events and azimuths, with the exception of the measurements for the smaller events from European stations to the northeast. It is unclear whether these smaller events suffer from magnitude bias for the Love waves or whether the paths, which include the Caspian and Mediterranean, have variable attenuation for Love and Rayleigh waves. For the Korean Peninsula, we have estimated Rayleigh- and Love-wave magnitudes for 31 earthquakes and two nuclear explosions, including the 25 May 2009 event. For 25 of the earthquakes, the network-averaged Love-wave magnitude is larger than the Rayleigh-wave estimate. For the 2009 nuclear explosion, the Love-wave M{sub s} (VMAX) was 3.1 while the Rayleigh-wave magnitude was 3.6. We are also utilizing the potential of observed variances in M{sub s} estimates that differ significantly in earthquake and explosion populations. We have considered two possible methods for incorporating unequal variances into the discrimination problem and compared the performance of various approaches on a population of 73 western United States earthquakes and 131 Nevada Test Site explosions. The approach proposes replacing the M{sub s} component by M{sub s} + a* {sigma}, where {sigma} denotes the interstation standard deviation obtained from the stations in the sample that produced the M{sub s} value. We replace the usual linear discriminant a* M{sub s}+b*{sub m{sub b}} with a* M{sub s}+b*{sub m{sub b}} + C*{sigma}. In the second approach, we estimate the optimum hybrid linear-quadratic discriminant function resulting from the unequal variance assumption. We observed slight improvement for the discriminant functions resulting from the theoretical interpretations of the unequal variance function. We have also studied the complexity of the ''magnitude spectra'' at each station. Our hypothesis is that explosion spectra should have fewer focal mechanism-produced complexities in the magnitude spectra than earthquakes. We have developed an intrastation ''complexity'' metric {Delta}M{sub s}, where {Delta}M{sub s} = M{sub s}(i)-M{sub s}(i+1) at periods, i, which are between 9 and 25 seconds. The complexity by itself has discriminating power but does not add substantially to the conditional hybrid discriminant that incorporates the differing spreads of the earthquake and explosion standard deviations.« less
Retinoic Acid Signaling Affects Cortical Synchrony During Sleep
NASA Astrophysics Data System (ADS)
Maret, Stéphanie; Franken, Paul; Dauvilliers, Yves; Ghyselinck, Norbert B.; Chambon, Pierre; Tafti, Mehdi
2005-10-01
Delta oscillations, characteristic of the electroencephalogram (EEG) of slow wave sleep, estimate sleep depth and need and are thought to be closely linked to the recovery function of sleep. The cellular mechanisms underlying the generation of delta waves at the cortical and thalamic levels are well documented, but the molecular regulatory mechanisms remain elusive. Here we demonstrate in the mouse that the gene encoding the retinoic acid receptor beta determines the contribution of delta oscillations to the sleep EEG. Thus, retinoic acid signaling, which is involved in the patterning of the brain and dopaminergic pathways, regulates cortical synchrony in the adult.
Generation and Evolution of Internal Waves in Luzon Strait
2015-09-30
1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Generation and Evolution of Internal Waves in Luzon...inertial waves , nonlinear internal waves (NLIWs), and turbulence mixing––in the ocean and thereby help develop improved parameterizations of mixing for...ocean models. Mixing within the stratified ocean is a particular focus as the complex interplay of internal waves from a variety of sources and
Generation and Evolution of Internal Waves in Luzon Strait
2016-03-01
1 DISTRIBUTION STATEMENT A: Distribution approved for public release; distribution is unlimited. Generation and Evolution of Internal Waves in...internal tides, inertial waves , nonlinear internal waves (NLIWs), and turbulence mixing––in the ocean and thereby help develop improved parameterizations of...mixing for ocean models. Mixing within the stratified ocean is a particular focus as the complex interplay of internal waves from a variety of
Quantification of Beach Profile Change
1988-01-01
complex fluid motion over an irregular bottom, and absence of rigorous descriptions of broken waves and sediment-sediment interaction, also make the...monochromatic and irregular waves for a dune-like foreshore with and without a significant surf zone. For one case starting from a beach without...34foreshore", mono- chromatic waves produced a bar, whereas irregular waves of significant height and peak spectral period of the monochromatic waves did
Abou-Kheir, Wassim; Isaac, Beth; Yamaguchi, Hideki; Cox, Dianne
2008-02-01
Wiskott-Aldrich syndrome protein (WASP)-family verprolin homologous (WAVE) proteins play a major role in Rac-induced actin dynamics, but Rac does not bind directly to WAVE proteins. It has been proposed that either the insulin receptor substrate protein 53 (IRSp53) or a complex of proteins containing Abelson interactor protein 1 (Abi1) mediates the interaction of WAVE2 and Rac. Depletion of endogenous IRSp53 by RNA-mediated interference (RNAi) in a RAW/LR5 macrophage cell line resulted in a significant reduction of Rac1Q61L-induced surface ruffles and colony-stimulating factor 1 (CSF-1)-induced actin polymerization, protrusion and cell migration. However, IRSp53 was not essential for Fcgamma-R-mediated phagocytosis, formation of podosomes or for formation of Cdc42V12-induced filopodia. IRSp53 was found to be present in an immunoprecipitable complex with WAVE2 and Abi1 in a Rac1-activation-dependent manner in RAW/LR5 cells in vivo. Importantly, reduction of endogenous IRSp53 or expression of IRSp53 lacking the WAVE2-binding site (IRSp53DeltaSH3) resulted in a significant reduction in the association of Rac1 with WAVE2 and Abi1, indicating that the association of Rac1 with WAVE2 and Abi1 is IRSp53 dependent. While it has been proposed that WAVE2 activity is regulated by membrane recruitment, membrane targeting of WAVE2 in RAW/LR5 and Cos-7 cells did not induce actin polymerization or protrusion, suggesting that membrane recruitment was insufficient for regulation of WAVE2. Combined, these data suggest that IRSp53 links Rac1 to WAVE2 in vivo and its function is crucial for production of CSF-1-induced F-actin-rich protrusions and cell migration in macrophages. This study indicates that Rac1, along with IRSp53 and Abi1, is involved in a more complex and tight regulation of WAVE2 than one operating solely through membrane localization.
Abou-Kheir, Wassim; Isaac, Beth; Yamaguchi, Hideki; Cox, Dianne
2009-01-01
Summary Wiskott-Aldrich syndrome protein (WASP)-family verprolin homologous (WAVE) proteins play a major role in Rac-induced actin dynamics, but Rac does not bind directly to WAVE proteins. It has been proposed that either the insulin receptor substrate protein 53 (IRSp53) or a complex of proteins containing Abelson interactor protein 1 (Abi1) mediate the interaction of WAVE2 and Rac. Depletion of endogenous IRSp53 by RNA-mediated interference (RNAi) in a RAW/LR5 macrophage cell line resulted in a significant reduction of Rac1Q61L-induced surface ruffles and colony stimulating factor-1 (CSF-1)-induced actin polymerization, protrusion, and cell migration. However, IRSp53 was not essential for Fcγ-R-mediated phagocytosis, formation of podosomes or for Cdc42V12-induced filopodia. IRSp53 was found to be present in an immunoprecipitatable complex with WAVE2 and Abi1 in a Rac1 activation-dependent manner in RAW/LR5 cells in vivo. Importantly, reduction of endogenous IRSp53 or expression of IRSp53 lacking the WAVE2 binding site (IRSp53ΔSH3) resulted in a significant reduction in the association of Rac1 with WAVE2 and Abi1, indicating that the association of Rac1 with WAVE2 and Abi1 is IRSp53 dependent. While it has been proposed that WAVE2 activity is regulated by membrane recruitment, membrane targeting of WAVE2 in RAW/LR5 and Cos-7 cells did not induce actin polymerization or protrusion suggesting thatt membrane recruitment was insufficient for WAVE2 regulation. Altogether, these data suggest that IRSp53 links Rac1 to WAVE2 in vivo and its function is crucial for CSF-1-induced F-actin rich protrusions and cell migration in macrophages. This study indicates that Rac1, along with IRSp53 and Abi1, is involved in a more complex and tight regulation of WAVE2 than solely through membrane localization. PMID:18198193
Molecular switch-like regulation in motor proteins.
Tafoya, Sara; Bustamante, Carlos
2018-06-19
Motor proteins are powered by nucleotide hydrolysis and exert mechanical work to carry out many fundamental biological tasks. To ensure their correct and efficient performance, the motors' activities are allosterically regulated by additional factors that enhance or suppress their NTPase activity. Here, we review two highly conserved mechanisms of ATP hydrolysis activation and repression operating in motor proteins-the glutamate switch and the arginine finger-and their associated regulatory factors. We examine the implications of these regulatory mechanisms in proteins that are formed by multiple ATPase subunits. We argue that the regulatory mechanisms employed by motor proteins display features similar to those described in small GTPases, which require external regulatory elements, such as dissociation inhibitors, exchange factors and activating proteins, to switch the protein's function 'on' and 'off'. Likewise, similar regulatory roles are taken on by the motor's substrate, additional binding factors, and even adjacent subunits in multimeric complexes. However, in motor proteins, more than one regulatory factor and the two mechanisms described here often underlie the machine's operation. Furthermore, ATPase regulation takes place throughout the motor's cycle, which enables a more complex function than the binary 'active' and 'inactive' states.This article is part of a discussion meeting issue 'Allostery and molecular machines'. © 2018 The Author(s).
Abduallah, Yasser; Turki, Turki; Byron, Kevin; Du, Zongxuan; Cervantes-Cervantes, Miguel; Wang, Jason T L
2017-01-01
Gene regulation is a series of processes that control gene expression and its extent. The connections among genes and their regulatory molecules, usually transcription factors, and a descriptive model of such connections are known as gene regulatory networks (GRNs). Elucidating GRNs is crucial to understand the inner workings of the cell and the complexity of gene interactions. To date, numerous algorithms have been developed to infer gene regulatory networks. However, as the number of identified genes increases and the complexity of their interactions is uncovered, networks and their regulatory mechanisms become cumbersome to test. Furthermore, prodding through experimental results requires an enormous amount of computation, resulting in slow data processing. Therefore, new approaches are needed to expeditiously analyze copious amounts of experimental data resulting from cellular GRNs. To meet this need, cloud computing is promising as reported in the literature. Here, we propose new MapReduce algorithms for inferring gene regulatory networks on a Hadoop cluster in a cloud environment. These algorithms employ an information-theoretic approach to infer GRNs using time-series microarray data. Experimental results show that our MapReduce program is much faster than an existing tool while achieving slightly better prediction accuracy than the existing tool.
Shock wave experiments on gallium
NASA Astrophysics Data System (ADS)
Jensen, Brian; Branch, Brittany; Cherne, Frank
2017-06-01
Gallium exhibits a complex phase diagram with multiple solid phases, an anomalous melt boundary, and a low-temperature melt transition making it a suitable material for shock wave studies focused on multiphase properties including kinetics and strength. Apart from high-pressure shock wave data that exists for the liquid phase, there is a clear lack of data in the low-pressure regime where much of the complexity in the phase diagram exists. In this work, a series of shock wave experiments were performed to begin examining the low-pressure region of the phase diagram. Additional data on a gallium alloy, which remains liquid at room temperature, will be presented and compared to data available for pure gallium (LA-UR-17-21449).
Measurement of physical characteristics of materials by ultrasonic methods
Lu, Wei-yang; Min, Shermann
1998-01-01
A method is described for determining and evaluating physical characteristics of a material. In particular, the present invention provides for determining and evaluating the anisotropic characteristics of materials, especially those resulting from such manufacturing processes as rolling, forming, extruding, drawing, forging, etc. In operation, a complex ultrasonic wave is created in the material of interest by any method. The wave form may be any combination of wave types and modes and is not limited to fundamental plate modes. The velocity of propagation of selected components which make up the complex ultrasonic wave are measured and evaluated to determine the physical characteristics of the material including, texture, strain/stress, grain size, crystal structure, etc.
Measurement of physical characteristics of materials by ultrasonic methods
Lu, W.Y.; Min, S.
1998-09-08
A method is described for determining and evaluating physical characteristics of a material. In particular, the present invention provides for determining and evaluating the anisotropic characteristics of materials, especially those resulting from such manufacturing processes as rolling, forming, extruding, drawing, forging, etc. In operation, a complex ultrasonic wave is created in the material of interest by any method. The wave form may be any combination of wave types and modes and is not limited to fundamental plate modes. The velocity of propagation of selected components which make up the complex ultrasonic wave are measured and evaluated to determine the physical characteristics of the material including, texture, strain/stress, grain size, crystal structure, etc. 14 figs.
Wang, Jiguang; Sun, Yidan; Zheng, Si; Zhang, Xiang-Sun; Zhou, Huarong; Chen, Luonan
2013-01-01
Synergistic interactions among transcription factors (TFs) and their cofactors collectively determine gene expression in complex biological systems. In this work, we develop a novel graphical model, called Active Protein-Gene (APG) network model, to quantify regulatory signals of transcription in complex biomolecular networks through integrating both TF upstream-regulation and downstream-regulation high-throughput data. Firstly, we theoretically and computationally demonstrate the effectiveness of APG by comparing with the traditional strategy based only on TF downstream-regulation information. We then apply this model to study spontaneous type 2 diabetic Goto-Kakizaki (GK) and Wistar control rats. Our biological experiments validate the theoretical results. In particular, SP1 is found to be a hidden TF with changed regulatory activity, and the loss of SP1 activity contributes to the increased glucose production during diabetes development. APG model provides theoretical basis to quantitatively elucidate transcriptional regulation by modelling TF combinatorial interactions and exploiting multilevel high-throughput information.
Wang, Jiguang; Sun, Yidan; Zheng, Si; Zhang, Xiang-Sun; Zhou, Huarong; Chen, Luonan
2013-01-01
Synergistic interactions among transcription factors (TFs) and their cofactors collectively determine gene expression in complex biological systems. In this work, we develop a novel graphical model, called Active Protein-Gene (APG) network model, to quantify regulatory signals of transcription in complex biomolecular networks through integrating both TF upstream-regulation and downstream-regulation high-throughput data. Firstly, we theoretically and computationally demonstrate the effectiveness of APG by comparing with the traditional strategy based only on TF downstream-regulation information. We then apply this model to study spontaneous type 2 diabetic Goto-Kakizaki (GK) and Wistar control rats. Our biological experiments validate the theoretical results. In particular, SP1 is found to be a hidden TF with changed regulatory activity, and the loss of SP1 activity contributes to the increased glucose production during diabetes development. APG model provides theoretical basis to quantitatively elucidate transcriptional regulation by modelling TF combinatorial interactions and exploiting multilevel high-throughput information. PMID:23346354
Weidmann, Chase A; Qiu, Chen; Arvola, René M; Lou, Tzu-Fang; Killingsworth, Jordan; Campbell, Zachary T; Tanaka Hall, Traci M; Goldstrohm, Aaron C
2016-08-02
Collaboration among the multitude of RNA-binding proteins (RBPs) is ubiquitous, yet our understanding of these key regulatory complexes has been limited to single RBPs. We investigated combinatorial translational regulation by Drosophila Pumilio (Pum) and Nanos (Nos), which control development, fertility, and neuronal functions. Our results show how the specificity of one RBP (Pum) is modulated by cooperative RNA recognition with a second RBP (Nos) to synergistically repress mRNAs. Crystal structures of Nos-Pum-RNA complexes reveal that Nos embraces Pum and RNA, contributes sequence-specific contacts, and increases Pum RNA-binding affinity. Nos shifts the recognition sequence and promotes repression complex formation on mRNAs that are not stably bound by Pum alone, explaining the preponderance of sub-optimal Pum sites regulated in vivo. Our results illuminate the molecular mechanism of a regulatory switch controlling crucial gene expression programs, and provide a framework for understanding how the partnering of RBPs evokes changes in binding specificity that underlie regulatory network dynamics.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Weidmann, Chase A.; Qiu, Chen; Arvola, René M.
Collaboration among the multitude of RNA-binding proteins (RBPs) is ubiquitous, yet our understanding of these key regulatory complexes has been limited to single RBPs. We investigated combinatorial translational regulation byDrosophilaPumilio (Pum) and Nanos (Nos), which control development, fertility, and neuronal functions. Our results show how the specificity of one RBP (Pum) is modulated by cooperative RNA recognition with a second RBP (Nos) to synergistically repress mRNAs. Crystal structures of Nos-Pum-RNA complexes reveal that Nos embraces Pum and RNA, contributes sequence-specific contacts, and increases Pum RNA-binding affinity. Nos shifts the recognition sequence and promotes repression complex formation on mRNAs that aremore » not stably bound by Pum alone, explaining the preponderance of sub-optimal Pum sites regulatedin vivo. Our results illuminate the molecular mechanism of a regulatory switch controlling crucial gene expression programs, and provide a framework for understanding how the partnering of RBPs evokes changes in binding specificity that underlie regulatory network dynamics.« less
Dark- and bright-rogue-wave solutions for media with long-wave-short-wave resonance.
Chen, Shihua; Grelu, Philippe; Soto-Crespo, J M
2014-01-01
Exact explicit rogue-wave solutions of intricate structures are presented for the long-wave-short-wave resonance equation. These vector parametric solutions feature coupled dark- and bright-field counterparts of the Peregrine soliton. Numerical simulations show the robustness of dark and bright rogue waves in spite of the onset of modulational instability. Dark fields originate from the complex interplay between anomalous dispersion and the nonlinearity driven by the coupled long wave. This unusual mechanism, not available in scalar nonlinear wave equation models, can provide a route to the experimental realization of dark rogue waves in, for instance, negative index media or with capillary-gravity waves.
Influence of San Gabriel submarine canyon on narrow-shelf sediment dynamics, southern California
Karl, Herman A.
1980-01-01
A conceptual model attributes the PTC to modification of shelf circulation patterns by San Gabriel Canyon. Surface waves diverge over the canyon head resulting in differential wave set up at the shore face. This forces back turbid nearshore water for a distance of a few kilometers toward the canyon. At some point on the shelf, seaward nearshore flow overlaps offshore currents generated or modified by internal waves focused onto the shelf by the canyon and/or turbulent eddies produced by flow separation in currents moving across the canyon axis. At times, these subtle processes overprint tidal and wind-driven currents and thereby create the PTC. The model suggests that canyons heading several kilometers from shore can have a regulatory effect on narrow-shelf sediment dynamics.
NASA Astrophysics Data System (ADS)
Ravindran, Vandana; Sunitha, V.; Bagler, Ganesh
2017-05-01
Cancer is characterized by a complex web of regulatory mechanisms which makes it difficult to identify features that are central to its control. Molecular integrative models of cancer, generated with the help of data from experimental assays, facilitate use of control theory to probe for ways of controlling the state of such a complex dynamic network. We modeled the human cancer signaling network as a directed graph and analyzed it for its controllability, identification of driver nodes and their characterization. We identified the driver nodes using the maximum matching algorithm and classified them as backbone, peripheral and ordinary based on their role in regulatory interactions and control of the network. We found that the backbone driver nodes were key to driving the regulatory network into cancer phenotype (via mutations) as well as for steering into healthy phenotype (as drug targets). This implies that while backbone genes could lead to cancer by virtue of mutations, they are also therapeutic targets of cancer. Further, based on their impact on the size of the set of driver nodes, genes were characterized as indispensable, dispensable and neutral. Indispensable nodes within backbone of the network emerged as central to regulatory mechanisms of control of cancer. In addition to probing the cancer signaling network from the perspective of control, our findings suggest that indispensable backbone driver nodes could be potentially leveraged as therapeutic targets. This study also illustrates the application of structural controllability for studying the mechanisms underlying the regulation of complex diseases.
NASA Astrophysics Data System (ADS)
Bekki, Naoaki; Shintani, Seine A.; Ishiwata, Shin'ichi; Kanai, Hiroshi
2016-04-01
We observe traveling waves, measured by the ultrasonic noninvasive imaging method, in a longitudinal beam direction from the apex to the base side on the interventricular septum (IVS) during the period from the end-diastole to the beginning of systole for a healthy human heart wall. We present a possible phenomenological model to explain part of one-dimensional cardiac behaviors for the observed traveling waves around the time of R-wave of echocardiography (ECG) in the human heart. Although the observed two-dimensional patterns of traveling waves are extremely complex and no one knows yet the exact solutions for the traveling homoclinic plane wave in the one-dimensional complex Ginzburg-Landau equation (CGLE), we numerically find that part of the one-dimensional homoclinic dynamics of the phase and amplitude patterns in the observed traveling waves is similar to that of the numerical homoclinic plane-wave solutions in the CGLE with periodic boundary condition in a certain parameter space. It is suggested that part of the cardiac dynamics of the traveling waves on the IVS can be qualitatively described by the CGLE model as a paradigm for understanding biophysical nonlinear phenomena.
Leckey, Cara A C; Rogge, Matthew D; Raymond Parker, F
2014-01-01
Three-dimensional (3D) elastic wave simulations can be used to investigate and optimize nondestructive evaluation (NDE) and structural health monitoring (SHM) ultrasonic damage detection techniques for aerospace materials. 3D anisotropic elastodynamic finite integration technique (EFIT) has been implemented for ultrasonic waves in carbon fiber reinforced polymer (CFRP) composite laminates. This paper describes 3D EFIT simulations of guided wave propagation in undamaged and damaged anisotropic and quasi-isotropic composite plates. Comparisons are made between simulations of guided waves in undamaged anisotropic composite plates and both experimental laser Doppler vibrometer (LDV) wavefield data and dispersion curves. Time domain and wavenumber domain comparisons are described. Wave interaction with complex geometry delamination damage is then simulated to investigate how simulation tools incorporating realistic damage geometries can aid in the understanding of wave interaction with CFRP damage. In order to move beyond simplistic assumptions of damage geometry, volumetric delamination data acquired via X-ray microfocus computed tomography is directly incorporated into the simulation. Simulated guided wave interaction with the complex geometry delamination is compared to experimental LDV time domain data and 3D wave interaction with the volumetric damage is discussed. Published by Elsevier B.V.
Modularity and design principles in the sea urchin embryo gene regulatory network
Peter, Isabelle S.; Davidson, Eric H.
2010-01-01
The gene regulatory network (GRN) established experimentally for the pre-gastrular sea urchin embryo provides causal explanations of the biological functions required for spatial specification of embryonic regulatory states. Here we focus on the structure of the GRN which controls the progressive increase in complexity of territorial regulatory states during embryogenesis; and on the types of modular subcircuits of which the GRN is composed. Each of these subcircuit topologies executes a particular operation of spatial information processing. The GRN architecture reflects the particular mode of embryogenesis represented by sea urchin development. Network structure not only specifies the linkages constituting the genomic regulatory code for development, but also indicates the various regulatory requirements of regional developmental processes. PMID:19932099
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chou, Chia-Chun, E-mail: ccchou@mx.nthu.edu.tw
2014-03-14
The complex quantum Hamilton-Jacobi equation-Bohmian trajectories (CQHJE-BT) method is introduced as a synthetic trajectory method for integrating the complex quantum Hamilton-Jacobi equation for the complex action function by propagating an ensemble of real-valued correlated Bohmian trajectories. Substituting the wave function expressed in exponential form in terms of the complex action into the time-dependent Schrödinger equation yields the complex quantum Hamilton-Jacobi equation. We transform this equation into the arbitrary Lagrangian-Eulerian version with the grid velocity matching the flow velocity of the probability fluid. The resulting equation describing the rate of change in the complex action transported along Bohmian trajectories is simultaneouslymore » integrated with the guidance equation for Bohmian trajectories, and the time-dependent wave function is readily synthesized. The spatial derivatives of the complex action required for the integration scheme are obtained by solving one moving least squares matrix equation. In addition, the method is applied to the photodissociation of NOCl. The photodissociation dynamics of NOCl can be accurately described by propagating a small ensemble of trajectories. This study demonstrates that the CQHJE-BT method combines the considerable advantages of both the real and the complex quantum trajectory methods previously developed for wave packet dynamics.« less
Utilizing the GentleWave® System for Debridement of Undetected Apical Anatomy.
Ford, Michael W
2018-03-01
Debriding and disinfecting complex anatomies within the root canal system pose a major challenge during root canal therapy. Even with current chemomechanical techniques, debris and bacterial remnants are commonly left behind, which are generally believed to increase the risk of endodontic failure. This case details the use of a new technique to debride complex apical anatomy in a maxillary molar. A 48-year-old female presented to the clinic with a chief complaint of increasing pain in her tooth. Clinical examination of the right first maxillary molar (#3) revealed moderate sensitivity to percussion and mild sensitivity to palpation. A pulpal diagnosis of symptomatic irreversible pulpitis and a periapi-cal diagnosis of symptomatic apical periodontitis were made. Mechanical instrumentation was performed using rotary file size #25/.04 for the mesiobuccal and distobuccal canals and size #25/.06 for the palatal canal to create a fluid path and enable obturation of the root canal system following the GentleWave® Procedure. The GentleWave Procedure was completed using Multisonic Ultracleaning™ for complete debridement and disinfection of the root canal system. The tooth was obturated using a warm vertical continuous wave obturation technique. Postoperative radiographs revealed complex anatomy within the apical third that was undetected both during pre-operative radiography and mechanical instrumentation. The palatal canal exhibited a complex apical delta with multiple points of exit, and the mesiobuccal canal revealed an undetected lateral canal within the apical third that had a separate and distinct egress. Conclusion and clinical significance: It is important for the clinician to debride and disinfect complex anatomy within the root canal system to reduce the risk of endodontic failure. This case report highlights the clinical significance of utilizing the GentleWave Procedure for detecting complex apical anatomy during endodontic therapy.
NASA Astrophysics Data System (ADS)
Kamegai, Kazuhisa; Sakai, Takeshi; Sakai, Nami; Hirota, Tomoya; Yamamoto, Satoshi
2013-03-01
Submillimeter-wave observations of complex organic molecules toward southern massive star forming regions were carried out with ASTE 10m telescope. Methyl formate (HCOOCH3) and dimethyl ether (CH3OCH3) were detected in some molecular cloud cores with young protostars. Differences in chemical composition among neighboring cores were also found.
ERIC Educational Resources Information Center
Jupp, James C.; Lensmire, Timothy J.
2016-01-01
In this article, we introduce our special issue, "Second-Wave White Teacher Identity Studies: Toward Complexity and Reflexivity in the Racial Conscientization of White Teachers." We characterize white teacher identity studies as a developing field with important implications for education research and teacher education. Early work in…
Lorentz-boosted evanescent waves
NASA Astrophysics Data System (ADS)
Bliokh, Konstantin Y.
2018-06-01
Polarization, spin, and helicity are important properties of electromagnetic waves. It is commonly believed that helicity is invariant under the Lorentz transformations. This is indeed so for plane waves and their localized superpositions. However, this is not the case for evanescent waves, which are well-defined only in a half-space, and are characterized by complex wave vectors. Here we describe transformations of evanescent electromagnetic waves and their polarization/spin/helicity properties under the Lorentz boosts along the three spatial directions.
Modeling Tsunami Wave Generation Using a Two-layer Granular Landslide Model
NASA Astrophysics Data System (ADS)
Ma, G.; Kirby, J. T., Jr.; Shi, F.; Grilli, S. T.; Hsu, T. J.
2016-12-01
Tsunamis can be generated by subaerial or submarine landslides in reservoirs, lakes, fjords, bays and oceans. Compared to seismogenic tsunamis, landslide or submarine mass failure (SMF) tsunamis are normally characterized by relatively shorter wave lengths and stronger wave dispersion, and potentially may generate large wave amplitudes locally and high run-up along adjacent coastlines. Due to a complex interplay between the landslide and tsunami waves, accurate simulation of landslide motion as well as tsunami generation is a challenging task. We develop and test a new two-layer model for granular landslide motion and tsunami wave generation. The landslide is described as a saturated granular flow, accounting for intergranular stresses governed by Coulomb friction. Tsunami wave generation is simulated by the three-dimensional non-hydrostatic wave model NHWAVE, which is capable of capturing wave dispersion efficiently using a small number of discretized vertical levels. Depth-averaged governing equations for the granular landslide are derived in a slope-oriented coordinate system, taking into account the dynamic interaction between the lower-layer granular landslide and upper-layer water motion. The model is tested against laboratory experiments on impulsive wave generation by subaerial granular landslides. Model results illustrate a complex interplay between the granular landslide and tsunami waves, and they reasonably predict not only the tsunami wave generation but also the granular landslide motion from initiation to deposition.
30 CFR 717.18 - Dams constructed of or impounding waste material.
Code of Federal Regulations, 2012 CFR
2012-07-01
... at least 3 feet to avoid overtopping by wind and wave action. (iii) Dams shall have minimum safety... pressures, internal erosion, sloughing, removal of material by solution, or erosion of material by loss into... regulatory authority before construction begins. (8) All dams shall be removed and the disturbed areas...
30 CFR 717.18 - Dams constructed of or impounding waste material.
Code of Federal Regulations, 2014 CFR
2014-07-01
... at least 3 feet to avoid overtopping by wind and wave action. (iii) Dams shall have minimum safety... pressures, internal erosion, sloughing, removal of material by solution, or erosion of material by loss into... regulatory authority before construction begins. (8) All dams shall be removed and the disturbed areas...
30 CFR 717.18 - Dams constructed of or impounding waste material.
Code of Federal Regulations, 2013 CFR
2013-07-01
... at least 3 feet to avoid overtopping by wind and wave action. (iii) Dams shall have minimum safety... pressures, internal erosion, sloughing, removal of material by solution, or erosion of material by loss into... regulatory authority before construction begins. (8) All dams shall be removed and the disturbed areas...
Kyrchanova, Olga; Mogila, Vladic; Wolle, Daniel; Deshpande, Girish; Parshikov, Alexander; Cléard, Fabienne; Karch, Francois; Schedl, Paul; Georgiev, Pavel
2016-07-01
Functionally autonomous regulatory domains direct the parasegment-specific expression of the Drosophila Bithorax complex (BX-C) homeotic genes. Autonomy is conferred by boundary/insulator elements that separate each regulatory domain from its neighbors. For six of the nine parasegment (PS) regulatory domains in the complex, at least one boundary is located between the domain and its target homeotic gene. Consequently, BX-C boundaries must not only block adventitious interactions between neighboring regulatory domains, but also be permissive (bypass) for regulatory interactions between the domains and their gene targets. To elucidate how the BX-C boundaries combine these two contradictory activities, we have used a boundary replacement strategy. We show that a 337 bp fragment spanning the Fab-8 boundary nuclease hypersensitive site and lacking all but 83 bp of the 625 bp Fab-8 PTS (promoter targeting sequence) fully rescues a Fab-7 deletion. It blocks crosstalk between the iab-6 and iab-7 regulatory domains, and has bypass activity that enables the two downstream domains, iab-5 and iab-6, to regulate Abdominal-B (Abd-B) transcription in spite of two intervening boundary elements. Fab-8 has two dCTCF sites and we show that they are necessary both for blocking and bypass activity. However, CTCF sites on their own are not sufficient for bypass. While multimerized dCTCF (or Su(Hw)) sites have blocking activity, they fail to support bypass. Moreover, this bypass defect is not rescued by the full length PTS. Finally, we show that orientation is critical for the proper functioning the Fab-8 replacement. Though the inverted Fab-8 boundary still blocks crosstalk, it disrupts the topology of the Abd-B regulatory domains and does not support bypass. Importantly, altering the orientation of the Fab-8 dCTCF sites is not sufficient to disrupt bypass, indicating that orientation dependence is conferred by other factors.
Wolle, Daniel; Deshpande, Girish; Parshikov, Alexander; Cléard, Fabienne; Karch, Francois; Schedl, Paul; Georgiev, Pavel
2016-01-01
Functionally autonomous regulatory domains direct the parasegment-specific expression of the Drosophila Bithorax complex (BX-C) homeotic genes. Autonomy is conferred by boundary/insulator elements that separate each regulatory domain from its neighbors. For six of the nine parasegment (PS) regulatory domains in the complex, at least one boundary is located between the domain and its target homeotic gene. Consequently, BX-C boundaries must not only block adventitious interactions between neighboring regulatory domains, but also be permissive (bypass) for regulatory interactions between the domains and their gene targets. To elucidate how the BX-C boundaries combine these two contradictory activities, we have used a boundary replacement strategy. We show that a 337 bp fragment spanning the Fab-8 boundary nuclease hypersensitive site and lacking all but 83 bp of the 625 bp Fab-8 PTS (promoter targeting sequence) fully rescues a Fab-7 deletion. It blocks crosstalk between the iab-6 and iab-7 regulatory domains, and has bypass activity that enables the two downstream domains, iab-5 and iab-6, to regulate Abdominal-B (Abd-B) transcription in spite of two intervening boundary elements. Fab-8 has two dCTCF sites and we show that they are necessary both for blocking and bypass activity. However, CTCF sites on their own are not sufficient for bypass. While multimerized dCTCF (or Su(Hw)) sites have blocking activity, they fail to support bypass. Moreover, this bypass defect is not rescued by the full length PTS. Finally, we show that orientation is critical for the proper functioning the Fab-8 replacement. Though the inverted Fab-8 boundary still blocks crosstalk, it disrupts the topology of the Abd-B regulatory domains and does not support bypass. Importantly, altering the orientation of the Fab-8 dCTCF sites is not sufficient to disrupt bypass, indicating that orientation dependence is conferred by other factors. PMID:27428541
Federal Register 2010, 2011, 2012, 2013, 2014
2012-07-17
... to market participants that add or remove liquidity in the complex order book (``maker/taker fees and... quotations for complex order strategies in the complex order book.\\8\\ Given this enhancement to the complex... Customer orders, the Exchange has adopted maker fees that apply to transactions in the complex order book...
Federal Register 2010, 2011, 2012, 2013, 2014
2012-01-31
... order type, the legging order, is designed to increase the opportunities for a complex order resting on.... Description A complex order resting on ISE's complex order book may be executed either by: (i) Trading against an incoming complex order that is marketable against the resting complex order, or (ii) legging into...
Federal Register 2010, 2011, 2012, 2013, 2014
2010-01-14
... complex order auction (COA) and book (COB) rule. The COA system facilitates the handling and execution of complex orders by allowing for complex orders to rest in the system and allowing for inbound complex... order), and the stock component of a stock-option complex order handled by the system is executed on...
Chatterjee, Sumantra; Kapoor, Ashish; Akiyama, Jennifer A.; ...
2016-09-29
Common sequence variants in cis-regulatory elements (CREs) are suspected etiological causes of complex disorders. We previously identified an intronic enhancer variant in the RET gene disrupting SOX10 binding and increasing Hirschsprung disease (HSCR) risk 4-fold. We now show that two other functionally independent CRE variants, one binding Gata2 and the other binding Rarb, also reduce Ret expression and increase risk 2- and 1.7-fold. By studying human and mouse fetal gut tissues and cell lines, we demonstrate that reduced RET expression propagates throughout its gene regulatory network, exerting effects on both its positive and negative feedback components. We also provide evidencemore » that the presence of a combination of CRE variants synergistically reduces RET expression and its effects throughout the GRN. These studies show how the effects of functionally independent non-coding variants in a coordinated gene regulatory network amplify their individually small effects, providing a model for complex disorders.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chatterjee, Sumantra; Kapoor, Ashish; Akiyama, Jennifer A.
Common sequence variants in cis-regulatory elements (CREs) are suspected etiological causes of complex disorders. We previously identified an intronic enhancer variant in the RET gene disrupting SOX10 binding and increasing Hirschsprung disease (HSCR) risk 4-fold. We now show that two other functionally independent CRE variants, one binding Gata2 and the other binding Rarb, also reduce Ret expression and increase risk 2- and 1.7-fold. By studying human and mouse fetal gut tissues and cell lines, we demonstrate that reduced RET expression propagates throughout its gene regulatory network, exerting effects on both its positive and negative feedback components. We also provide evidencemore » that the presence of a combination of CRE variants synergistically reduces RET expression and its effects throughout the GRN. These studies show how the effects of functionally independent non-coding variants in a coordinated gene regulatory network amplify their individually small effects, providing a model for complex disorders.« less
A systematic analysis of a mi-RNA inter-pathway regulatory motif
2013-01-01
Background The continuing discovery of new types and functions of small non-coding RNAs is suggesting the presence of regulatory mechanisms far more complex than the ones currently used to study and design Gene Regulatory Networks. Just focusing on the roles of micro RNAs (miRNAs), they have been found to be part of several intra-pathway regulatory motifs. However, inter-pathway regulatory mechanisms have been often neglected and require further investigation. Results In this paper we present the result of a systems biology study aimed at analyzing a high-level inter-pathway regulatory motif called Pathway Protection Loop, not previously described, in which miRNAs seem to play a crucial role in the successful behavior and activation of a pathway. Through the automatic analysis of a large set of public available databases, we found statistical evidence that this inter-pathway regulatory motif is very common in several classes of KEGG Homo Sapiens pathways and concurs in creating a complex regulatory network involving several pathways connected by this specific motif. The role of this motif seems also confirmed by a deeper review of other research activities on selected representative pathways. Conclusions Although previous studies suggested transcriptional regulation mechanism at the pathway level such as the Pathway Protection Loop, a high-level analysis like the one proposed in this paper is still missing. The understanding of higher-level regulatory motifs could, as instance, lead to new approaches in the identification of therapeutic targets because it could unveil new and “indirect” paths to activate or silence a target pathway. However, a lot of work still needs to be done to better uncover this high-level inter-pathway regulation including enlarging the analysis to other small non-coding RNA molecules. PMID:24152805
Knowles, Lori; Luth, Westerly; Bubela, Tania
2017-01-01
Abstract Personalized medicine (PM) aims to harness a wave of ‘omics’ discoveries to facilitate research and discovery of targeted diagnostics and therapies and increase the efficiency of healthcare systems by predicting and treating individual predispositions to diseases or conditions. Despite significant investment, limited progress has been made bringing PM to market. We describe the major perceived regulatory, intellectual property, and reimbursement challenges to the development, translation, adoption, and implementation of PM products into clinical care. We conducted a scoping review to identify (i) primary challenges for the development and implementation of PM identified in the academic literature; (ii) solutions proposed in the academic literature to address these challenges; and (iii) gaps that exist in that literature. We identified regulatory barriers to PM development and recommendations in 344 academic papers. Regulatory uncertainty was a cross-cutting theme that appeared in conjunction with other themes including: reimbursement; clinical trial regulation; regulation of co-development; unclear evidentiary requirements; insufficient incentives for research and development; incompatible information systems; and different regulation of different diagnostics. To fully realize the benefits of PM for healthcare systems and patients, regulatory, intellectual property, and reimbursement challenges need to be addressed in lock step with scientific advances. PMID:29868182
Simple determinant representation for rogue waves of the nonlinear Schrödinger equation.
Ling, Liming; Zhao, Li-Chen
2013-10-01
We present a simple representation for arbitrary-order rogue wave solution and a study on the trajectories of them explicitly. We find that the trajectories of two valleys on whole temporal-spatial distribution all look "X" -shaped for rogue waves. Additionally, we present different types of high-order rogue wave structures, which could be helpful towards realizing the complex dynamics of rogue waves.
Theory of Electromagnetic Surface Waves in Plasma with Smooth Boundaries
NASA Astrophysics Data System (ADS)
Kuzelev, M. V.
2018-05-01
A theory of nonpotential surface waves in plasma with smooth boundaries is developed. The complex frequencies of surface waves for plasma systems of different geometries and different profiles of the plasma density are calculated. Expressions for the rates of collisionless damping of surface waves due to their resonance interaction with local plasma waves of continuous spectrum are obtained. The influence of collisions in plasma is also considered.
Measurement of the complex permittivity of low loss polymer powders in the millimeter-wave range.
Kapilevich, Boris; Litvak, Boris; Wainstein, Vladimir; Moshe, Danny
2007-01-01
An improved measurement method of complex permittivity of low loss polymer powders is suggested. The measurements are done in the mm-wave range using a quasi optical resonator. The 2-D corrugated mode exciter is employed to improve suppression of undesirable higher modes. The model used for reconstructing complex permittivity takes into account ohm losses of metal mesh coupling that provide better accuracy of the reconstructing procedure. An example illustrating this method is reported.
Delage, Elise; Cervantes, Diégo Cordero; Pénard, Esthel; Schmitt, Christine; Syan, Sylvie; Disanza, Andrea; Scita, Giorgio; Zurzolo, Chiara
2016-12-23
Tunneling Nanotubes (TNTs) are actin enriched filopodia-like protrusions that play a pivotal role in long-range intercellular communication. Different pathogens use TNT-like structures as "freeways" to propagate across cells. TNTs are also implicated in cancer and neurodegenerative diseases, making them promising therapeutic targets. Understanding the mechanism of their formation, and their relation with filopodia is of fundamental importance to uncover their physiological function, particularly since filopodia, differently from TNTs, are not able to mediate transfer of cargo between distant cells. Here we studied different regulatory complexes of actin, which play a role in the formation of both these structures. We demonstrate that the filopodia-promoting CDC42/IRSp53/VASP network negatively regulates TNT formation and impairs TNT-mediated intercellular vesicle transfer. Conversely, elevation of Eps8, an actin regulatory protein that inhibits the extension of filopodia in neurons, increases TNT formation. Notably, Eps8-mediated TNT induction requires Eps8 bundling but not its capping activity. Thus, despite their structural similarities, filopodia and TNTs form through distinct molecular mechanisms. Our results further suggest that a switch in the molecular composition in common actin regulatory complexes is critical in driving the formation of either type of membrane protrusion.
Fanconi Anemia Core Complex Gene Promoters Harbor Conserved Transcription Regulatory Elements
Meier, Daniel; Schindler, Detlev
2011-01-01
The Fanconi anemia (FA) gene family is a recent addition to the complex network of proteins that respond to and repair certain types of DNA damage in the human genome. Since little is known about the regulation of this novel group of genes at the DNA level, we characterized the promoters of the eight genes (FANCA, B, C, E, F, G, L and M) that compose the FA core complex. The promoters of these genes show the characteristic attributes of housekeeping genes, such as a high GC content and CpG islands, a lack of TATA boxes and a low conservation. The promoters functioned in a monodirectional way and were, in their most active regions, comparable in strength to the SV40 promoter in our reporter plasmids. They were also marked by a distinctive transcriptional start site (TSS). In the 5′ region of each promoter, we identified a region that was able to negatively regulate the promoter activity in HeLa and HEK 293 cells in isolation. The central and 3′ regions of the promoter sequences harbor binding sites for several common and rare transcription factors, including STAT, SMAD, E2F, AP1 and YY1, which indicates that there may be cross-connections to several established regulatory pathways. Electrophoretic mobility shift assays and siRNA experiments confirmed the shared regulatory responses between the prominent members of the TGF-β and JAK/STAT pathways and members of the FA core complex. Although the promoters are not well conserved, they share region and sequence specific regulatory motifs and transcription factor binding sites (TBFs), and we identified a bi-partite nature to these promoters. These results support a hypothesis based on the co-evolution of the FA core complex genes that was expanded to include their promoters. PMID:21826217
Fanconi anemia core complex gene promoters harbor conserved transcription regulatory elements.
Meier, Daniel; Schindler, Detlev
2011-01-01
The Fanconi anemia (FA) gene family is a recent addition to the complex network of proteins that respond to and repair certain types of DNA damage in the human genome. Since little is known about the regulation of this novel group of genes at the DNA level, we characterized the promoters of the eight genes (FANCA, B, C, E, F, G, L and M) that compose the FA core complex. The promoters of these genes show the characteristic attributes of housekeeping genes, such as a high GC content and CpG islands, a lack of TATA boxes and a low conservation. The promoters functioned in a monodirectional way and were, in their most active regions, comparable in strength to the SV40 promoter in our reporter plasmids. They were also marked by a distinctive transcriptional start site (TSS). In the 5' region of each promoter, we identified a region that was able to negatively regulate the promoter activity in HeLa and HEK 293 cells in isolation. The central and 3' regions of the promoter sequences harbor binding sites for several common and rare transcription factors, including STAT, SMAD, E2F, AP1 and YY1, which indicates that there may be cross-connections to several established regulatory pathways. Electrophoretic mobility shift assays and siRNA experiments confirmed the shared regulatory responses between the prominent members of the TGF-β and JAK/STAT pathways and members of the FA core complex. Although the promoters are not well conserved, they share region and sequence specific regulatory motifs and transcription factor binding sites (TBFs), and we identified a bi-partite nature to these promoters. These results support a hypothesis based on the co-evolution of the FA core complex genes that was expanded to include their promoters.
Establishing an unusual cell type: How to make a dikaryon
Kruzel, Emilia K.; Hull, Christina M.
2010-01-01
Summary The dikaryons of basidiomycete fungi represent an unusual cell type required for complete sexual development. Dikaryon formation occurs via the activities of cell type-specific homeodomain transcription factors, which form regulatory complexes to establish the dikaryotic state. Decades of classical genetic and cell biological studies in mushrooms have provided a foundation for more recent molecular studies in the pathogenic species Ustilago maydis and Cryptococcus neoformans. Studies in these systems have revealed novel mechanisms of regulation that function downstream of classic homeodomain complexes to ensure that dikaryons are established and propagated. Comparisons of these dikaryon-specific networks promise to reveal the nature of regulatory network evolution and the adaptations responsible for driving complex eukaryotic development. PMID:21036099
Nadeau, Owen W.; Anderson, David W.; Yang, Qing; Artigues, Antonio; Paschall, Justin E.; Wyckoff, Gerald J.; McClintock, Jennifer L.; Carlson, Gerald M.
2007-01-01
Phosphorylase kinase (PhK), an (αβγδ)4 complex, regulates glycogenolysis. Its activity, catalyzed by the γ subunit, is tightly controlled by phosphorylation and activators acting through allosteric sites on its regulatory α, β and δ subunits. Activation of the catalytic γ subunit in the PhK complex by phosphorylation is known to be predominantly mediated by the regulatory β subunit, which undergoes a conformational change that is structurally linked with the γ subunit and that is characterized by the ability to form β-β dimers using a short chemical crosslinker. To determine potential regions of interaction of the β and γ subunits, we have used chemical crosslinking and 2-hybrid screening. The β and γ subunits were chemically crosslinked to each other in phosphorylated PhK, and crosslinked peptides were identified in digests of the kinase by Fourier transform mass spectrometry in combination with a search engine developed ‘in house’ that generates a hypothetical list of crosslinked peptides. Such a conjugate between β and γ was identified, verified by MS/MS and shown to correspond to crosslinking between K303 in the C-terminal regulatory domain of γ (γCRD) and R18 in the N-terminal regulatory region of β (β1-31), which contains the phosphorylatable serines 11 and 26. A synthetic peptide corresponding to residues 1-22 of β inhibited the crosslinking between β and γ in the complex, and was itself crosslinked to K303 of γ. Through the use of 2-hybrid screening, the β1-31 region was also shown to control β subunit self-interactions, which were favored by truncation of this region or by mutation of the phosphorylatable serines 11 and 26, thus providing structural evidence for a phosphorylation-dependent subunit communication network in the PhK complex involving at least these two regulatory regions of the β and γ subunits. The sum of our results considered together with previous findings implicates the γCRD as being an allosteric activation switch in PhK that interacts with all three of the enzyme’s regulatory subunits and is proximal to the active site cleft. PMID:17123541
Analytical tools for characterizing biopharmaceuticals and the implications for biosimilars
Berkowitz, Steven A.; Engen, John R.; Mazzeo, Jeffrey R.; Jones, Graham B.
2013-01-01
Biologics such as monoclonal antibodies are much more complex than small-molecule drugs, which raises challenging questions for the development and regulatory evaluation of follow-on versions of such biopharmaceutical products (also known as biosimilars) and their clinical use once patent protection for the pioneering biologic has expired. With the recent introduction of regulatory pathways for follow-on versions of complex biologics, the role of analytical technologies in comparing biosimilars with the corresponding reference product is attracting substantial interest in establishing the development requirements for biosimilars. Here, we discuss the current state of the art in analytical technologies to assess three characteristics of protein biopharmaceuticals that regulatory authorities have identified as being important in development strategies for biosimilars: post-translational modifications, three-dimensional structures and protein aggregation. PMID:22743980
NASA Astrophysics Data System (ADS)
Kohler, M. D.; Castillo, J.; Massari, A.; Clayton, R. W.
2017-12-01
Earthquake-induced motions recorded by spatially dense seismic arrays in buildings located in the northern Los Angeles basin suggest the presence of complex, amplified surface wave effects on the seismic demand of mid-rise buildings. Several moderate earthquakes produced large-amplitude, seismic energy with slow shear-wave velocities that cannot be explained or accurately modeled by any published 3D seismic velocity models or by Vs30 values. Numerical experiments are conducted to determine if sedimentary basin features are responsible for these rarely modeled and poorly documented contributions to seismic demand computations. This is accomplished through a physics-based wave propagation examination of the effects of different sedimentary basin geometries on the nonlinear response of a mid-rise structural model based on an existing, instrumented building. Using two-dimensional finite-difference predictive modeling, we show that when an earthquake focal depth is near the vertical edge of an elongated and relatively shallow sedimentary basin, dramatically amplified and complex surface waves are generated as a result of the waveguide effect introduced by this velocity structure. In addition, for certain source-receiver distances and basin geometries, body waves convert to secondary Rayleigh waves that propagate both at the free-surface interface and along the depth interface of the basin that show up as multiple large-amplitude arrivals. This study is motivated by observations from the spatially dense, high-sample-rate acceleration data recorded by the Community Seismic Network, a community-hosted strong-motion network, currently consisting of hundreds of sensors located in the southern California area. The results provide quantitative insight into the causative relationship between a sedimentary basin shape and the generation of Rayleigh waves at depth, surface waves at the free surface, scattered seismic energy, and the sensitivity of building responses to each of these.
Mohamed Salleh, Faridah Hani; Arif, Shereena Mohd; Zainudin, Suhaila; Firdaus-Raih, Mohd
2015-12-01
A gene regulatory network (GRN) is a large and complex network consisting of interacting elements that, over time, affect each other's state. The dynamics of complex gene regulatory processes are difficult to understand using intuitive approaches alone. To overcome this problem, we propose an algorithm for inferring the regulatory interactions from knock-out data using a Gaussian model combines with Pearson Correlation Coefficient (PCC). There are several problems relating to GRN construction that have been outlined in this paper. We demonstrated the ability of our proposed method to (1) predict the presence of regulatory interactions between genes, (2) their directionality and (3) their states (activation or suppression). The algorithm was applied to network sizes of 10 and 50 genes from DREAM3 datasets and network sizes of 10 from DREAM4 datasets. The predicted networks were evaluated based on AUROC and AUPR. We discovered that high false positive values were generated by our GRN prediction methods because the indirect regulations have been wrongly predicted as true relationships. We achieved satisfactory results as the majority of sub-networks achieved AUROC values above 0.5. Copyright © 2015 Elsevier Ltd. All rights reserved.
Maternal Prenatal Stress and Infant Regulatory Capacity in Mexican Americans
Lin, Betty; Crnic, Keith A.; Luecken, Linda J.; Gonzales, Nancy A.
2014-01-01
The early postpartum period lays important groundwork for later self-regulation as infants' dispositional traits interact with caregivers' co-regulatory behaviors to produce the earliest forms of self-regulation. Although emerging literature suggests that fetal exposure to maternal stress may be integral in determining child self-regulatory capacity, the complex pathways that characterize these early developmental processes remain unclear. The current study considers these complex, transactional processes in a low income, Mexican American sample. Data were collected from 295 Mexican American infants and their mothers during prenatal, 6- and 12-week postpartum home interviews. Mother reports of stress were obtained prenatally, and mother reports of infant temperament were obtained at 6 weeks. Observer ratings of maternal sensitivity and infant regulatory behaviors were obtained at the 6- and 12-week time points. Study results indicate that prenatal stress predicts higher levels of infant negativity and surgency, both of which directly or interactively predict later engagement in regulatory behaviors. Unexpectedly, prenatal stress also predicted more engagement in orienting, but not self-comforting behaviors. Advancing understandings about the nature of these developmental pathways may have significant implications for targets of early intervention in this high risk population. PMID:25113917
Subsonic leaky Rayleigh waves at liquid-solid interfaces.
Mozhaev, V G; Weihnacht, M
2002-05-01
The paper is devoted to the study of leaky Rayleigh waves at liquid-solid interfaces close to the border of the existence domain of these modes. The real and complex roots of the secular equation are computed for interface waves at the boundary between water and a binary isotropic alloy of gold and silver with continuously variable composition. The change of composition of the alloy allows one to cross a critical velocity for the existence of leaky waves. It is shown that, contrary to popular opinion, the critical velocity does not coincide with the phase velocity of bulk waves in liquid. The true threshold velocity is found to be smaller, the correction being of about 1.45%. Attention is also drawn to the fact that using the real part of the complex phase velocity as a velocity of leaky waves gives only approximate value. The most interesting feature of the waves under consideration is the presence of energy leakage in the subsonic range of the phase velocities where, at first glance, any radiation by harmonic waves is not permitted. A simple physical explanation of this radiation with due regard for inhomogeneity of radiated and radiating waves is given. The controversial question of the existence of leaky Rayleigh waves at a water/ice interface is reexamined. It is shown that the solution considered previously as a leaky wave is in fact the solution of the bulk-wave-reflection problem for inhomogeneous waves.
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The K-π+ S-wave from the D+→K-π+π+ decay
NASA Astrophysics Data System (ADS)
FOCUS Collaboration; Link, J. M.; Yager, P. M.; Anjos, J. C.; Bediaga, I.; Castromonte, C.; Machado, A. A.; Magnin, J.; Massafferri, A.; de Miranda, J. M.; Pepe, I. M.; Polycarpo, E.; Dos Reis, A. C.; Carrillo, S.; Cuautle, E.; Sánchez-Hernández, A.; Uribe, C.; Vázquez, F.; Agostino, L.; Cinquini, L.; Cumalat, J. P.; Frisullo, V.; O'Reilly, B.; Segoni, I.; Stenson, K.; Butler, J. N.; Cheung, H. W. K.; Chiodini, G.; Gaines, I.; Garbincius, P. H.; Garren, L. A.; Gottschalk, E.; Kasper, P. H.; Kreymer, A. E.; Kutschke, R.; Wang, M.; Benussi, L.; Bianco, S.; Fabbri, F. L.; Zallo, A.; Casimiro, E.; Reyes, M.; Cawlfield, C.; Kim, D. Y.; Rahimi, A.; Wiss, J.; Gardner, R.; Kryemadhi, A.; Chung, Y. S.; Kang, J. S.; Ko, B. R.; Kwak, J. W.; Lee, K. B.; Cho, K.; Park, H.; Alimonti, G.; Barberis, S.; Boschini, M.; Cerutti, A.; D'Angelo, P.; Dicorato, M.; Dini, P.; Edera, L.; Erba, S.; Inzani, P.; Leveraro, F.; Malvezzi, S.; Menasce, D.; Mezzadri, M.; Moroni, L.; Pedrini, D.; Pontoglio, C.; Prelz, F.; Rovere, M.; Sala, S.; Davenport, T. F.; Arena, V.; Boca, G.; Bonomi, G.; Gianini, G.; Liguori, G.; Pegna, D. Lopes; Merlo, M. M.; Pantea, D.; Ratti, S. P.; Riccardi, C.; Vitulo, P.; Göbel, C.; Otalora, J.; Hernandez, H.; Lopez, A. M.; Mendez, H.; Paris, A.; Quinones, J.; Ramirez, J. E.; Zhang, Y.; Wilson, J. R.; Handler, T.; Mitchell, R.; Engh, D.; Hosack, M.; Johns, W. E.; Luiggi, E.; Moore, J. E.; Nehring, M.; Sheldon, P. D.; Vaandering, E. W.; Webster, M.; Sheaff, M.
2009-10-01
Using data from FOCUS (E831) experiment at Fermilab, we present a model independent partial-wave analysis of the K-π+ S-wave amplitude from the decay D+→K-π+π+. The S-wave is a generic complex function to be determined directly from the data fit. The P- and D-waves are parameterized by a sum of Breit-Wigner amplitudes. The measurement of the S-wave amplitude covers the whole elastic range of the K-π+ system.
Setting monitoring objectives for landscape-size areas
Craig M. Olson; Dean Angelides
2000-01-01
The setting of objectives for monitoring schemes for landscape-size areas should be a complex task in today's regulatory and sociopolitical atmosphere. The technology available today, the regulatory environment, and the sociopolitical considerations require multiresource inventory and monitoring schemes, whether tile ownership is industrial or for preservation....
NASA Astrophysics Data System (ADS)
Bartlett, P. L.; Stelbovics, A. T.; Rescigno, T. N.; McCurdy, C. W.
2007-11-01
Calculations are reported for four-body electron-helium collisions and positron-hydrogen collisions, in the S-wave model, using the time-independent propagating exterior complex scaling (PECS) method. The PECS S-wave calculations for three-body processes in electron-helium collisions compare favourably with previous convergent close-coupling (CCC) and time-dependent exterior complex scaling (ECS) calculations, and exhibit smooth cross section profiles. The PECS four-body double-excitation cross sections are significantly different from CCC calculations and highlight the need for an accurate representation of the resonant helium final-state wave functions when undertaking these calculations. Results are also presented for positron-hydrogen collisions in an S-wave model using an electron-positron potential of V12 = - (8 + (r1 - r2)2)-1/2. This model is representative of the full problem, and the results demonstrate that ECS-based methods can accurately calculate scattering, ionization and positronium formation cross sections in this three-body rearrangement collision.
Complex dispersion relation of surface acoustic waves at a lossy metasurface
NASA Astrophysics Data System (ADS)
Schwan, Logan; Geslain, Alan; Romero-García, Vicente; Groby, Jean-Philippe
2017-01-01
The complex dispersion relation of surface acoustic waves (SAWs) at a lossy resonant metasurface is theoretically and experimentally reported. The metasurface consists of the periodic arrangement of borehole resonators in a rigid substrate. The theoretical model relies on a boundary layer approach that provides the effective metasurface admittance governing the complex dispersion relation in the presence of viscous and thermal losses. The model is experimentally validated by measurements in the semi-anechoic chamber. The complex SAW dispersion relation is experimentally retrieved from the analysis of the spatial Laplace transform of the pressure scanned along a line at the metasurface. The geometrical spreading of the energy from the speaker is accounted for, and both the real and imaginary parts of the SAW wavenumber are obtained. The results show that the strong reduction of the SAW group velocity occurs jointly with a drastic attenuation of the wave, leading to the confinement of the field close to the source and preventing the efficient propagation of such slow-sound surface modes. The method opens perspectives to theoretically predict and experimentally characterize both the dispersion and the attenuation of surface waves at structured surfaces.
Propagation and attenuation of Rayleigh waves in generalized thermoelastic media
NASA Astrophysics Data System (ADS)
Sharma, M. D.
2014-01-01
This study considers the propagation of Rayleigh waves in a generalized thermoelastic half-space with stress-free plane boundary. The boundary has the option of being either isothermal or thermally insulated. In either case, the dispersion equation is obtained in the form of a complex irrational expression due to the presence of radicals. This dispersion equation is rationalized into a polynomial equation, which is solvable, numerically, for exact complex roots. The roots of the dispersion equation are obtained after removing the extraneous zeros of this polynomial equation. Then, these roots are filtered out for the inhomogeneous propagation of waves decaying with depth. Numerical examples are solved to analyze the effects of thermal properties of elastic materials on the dispersion of existing surface waves. For these thermoelastic Rayleigh waves, the behavior of elliptical particle motion is studied inside and at the surface of the medium. Insulation of boundary does play a significant role in changing the speed, amplitude, and polarization of Rayleigh waves in thermoelastic media.
NASA Astrophysics Data System (ADS)
Diaz, A.; Ramos, J. G.; Friedman, J. S.
2017-09-01
We developed a web-based instructional and research tool that demonstrates the behavior of electromagnetic waves as they propagate through a homogenous medium and through an interface where the second medium can be characterized by an effective complex permittivity and permeability. Either p- or s-polarization wave components can be chosen and the graphical interface includes 2D wave and 3D component representations. The program enables the study of continuity of electromagnetic components, critical angle, Brewster angle, absorption and amplification, behavior of light in sub-unity and negative-index materials, Poynting vector and phase velocity behavior, and positive and negative Goos- Hänchen shifts.
Kristie, T M; LeBowitz, J H; Sharp, P A
1989-01-01
The herpes simplex virus transactivator, alpha TIF, stimulates transcription of the alpha/immediate early genes via a cis-acting site containing an octamer element and a conserved flanking sequence. The alpha TIF protein, produced in a baculovirus expression system, nucleates the formation of at least two DNA--protein complexes on this regulatory element. Both of these complexes contain the ubiquitous Oct-1 protein, whose POU domain alone is sufficient to allow assembly of the alpha TIF-dependent complexes. A second member of the POU domain family, the lymphoid specific Oct-2 protein, can also be assembled into similar complexes at high concentrations of alpha TIF protein. These complexes contain at least two cellular proteins in addition to Oct-1. One of these proteins is present in both insect and HeLa cells and probably recognizes sequences in the cis element. The second cellular protein, only present in HeLa cells, probably binds by protein-protein interactions. Images PMID:2556266
Kristie, T M; LeBowitz, J H; Sharp, P A
1989-12-20
The herpes simplex virus transactivator, alpha TIF, stimulates transcription of the alpha/immediate early genes via a cis-acting site containing an octamer element and a conserved flanking sequence. The alpha TIF protein, produced in a baculovirus expression system, nucleates the formation of at least two DNA--protein complexes on this regulatory element. Both of these complexes contain the ubiquitous Oct-1 protein, whose POU domain alone is sufficient to allow assembly of the alpha TIF-dependent complexes. A second member of the POU domain family, the lymphoid specific Oct-2 protein, can also be assembled into similar complexes at high concentrations of alpha TIF protein. These complexes contain at least two cellular proteins in addition to Oct-1. One of these proteins is present in both insect and HeLa cells and probably recognizes sequences in the cis element. The second cellular protein, only present in HeLa cells, probably binds by protein-protein interactions.
Walsh, Gregory S; Grant, Paul K; Morgan, John A; Moens, Cecilia B
2011-07-01
Components of the planar cell polarity (PCP) pathway are required for the caudal tangential migration of facial branchiomotor (FBM) neurons, but how PCP signaling regulates this migration is not understood. In a forward genetic screen, we identified a new gene, nhsl1b, required for FBM neuron migration. nhsl1b encodes a WAVE-homology domain-containing protein related to human Nance-Horan syndrome (NHS) protein and Drosophila GUK-holder (Gukh), which have been shown to interact with components of the WAVE regulatory complex that controls cytoskeletal dynamics and with the polarity protein Scribble, respectively. Nhsl1b localizes to FBM neuron membrane protrusions and interacts physically and genetically with Scrib to control FBM neuron migration. Using chimeric analysis, we show that FBM neurons have two modes of migration: one involving interactions between the neurons and their planar-polarized environment, and an alternative, collective mode involving interactions between the neurons themselves. We demonstrate that the first mode of migration requires the cell-autonomous functions of Nhsl1b and the PCP components Scrib and Vangl2 in addition to the non-autonomous functions of Scrib and Vangl2, which serve to polarize the epithelial cells in the environment of the migrating neurons. These results define a role for Nhsl1b as a neuronal effector of PCP signaling and indicate that proper FBM neuron migration is directly controlled by PCP signaling between the epithelium and the migrating neurons.
Walsh, Gregory S.; Grant, Paul K.; Morgan, John A.; Moens, Cecilia B.
2011-01-01
Components of the planar cell polarity (PCP) pathway are required for the caudal tangential migration of facial branchiomotor (FBM) neurons, but how PCP signaling regulates this migration is not understood. In a forward genetic screen, we identified a new gene, nhsl1b, required for FBM neuron migration. nhsl1b encodes a WAVE-homology domain-containing protein related to human Nance-Horan syndrome (NHS) protein and Drosophila GUK-holder (Gukh), which have been shown to interact with components of the WAVE regulatory complex that controls cytoskeletal dynamics and with the polarity protein Scribble, respectively. Nhsl1b localizes to FBM neuron membrane protrusions and interacts physically and genetically with Scrib to control FBM neuron migration. Using chimeric analysis, we show that FBM neurons have two modes of migration: one involving interactions between the neurons and their planar-polarized environment, and an alternative, collective mode involving interactions between the neurons themselves. We demonstrate that the first mode of migration requires the cell-autonomous functions of Nhsl1b and the PCP components Scrib and Vangl2 in addition to the non-autonomous functions of Scrib and Vangl2, which serve to polarize the epithelial cells in the environment of the migrating neurons. These results define a role for Nhsl1b as a neuronal effector of PCP signaling and indicate that proper FBM neuron migration is directly controlled by PCP signaling between the epithelium and the migrating neurons. PMID:21693519
Soap film vibration: origin of the dissipation.
Acharige, Sébastien Kosgodagan; Elias, Florence; Derec, Caroline
2014-11-07
We investigate the complex dispersion relationship of a transverse antisymmetric wave on a horizontal soap film. Experimentally, the complex wave number k at a fixed forcing frequency is determined by measuring the vibrating amplitude of the soap film: the wavelength (linked to the real part of k) is determined by the spatial variation of the amplitude; the decay length (linked to the imaginary part of k) is determined by analyzing the resonance curves of the vibrating wave as a function of frequency. Theoretically, we compute the complex dispersion relationship taking into account the physical properties of the bulk liquid and gas phase, and of the gas-liquid interfaces. The comparison between the computation (developed to the leading order under our experimental conditions) and the experimental results confirms that the phase velocity is fixed by the interplay between surface tension, and liquid and air inertia, as reported in previous studies. Moreover, we show that the attenuation of the transverse antisymmetric wave originates from the viscous dissipation in the gas phase surrounding the liquid film. This result is an important step in understanding the propagation of an acoustic wave in liquid foam, using a bottom-up approach.
Incident wave run-up into narrow sloping bays and estuaries
NASA Astrophysics Data System (ADS)
Sinan Özeren, M.; Postacioglu, Nazmi; Canlı, Umut
2015-04-01
The problem is investigated using Carrier Greenspan hodograph transformations.We perform a quasi-one-dimensional solution well into the bay, far enough of the mouth of the bay. The linearized boundary conditions at the mouth of the bay lead to an integral equation for 2-D geometry. A semi analytical optimization method has been developed to solve this integral equation. When the wavelength of the incident wave is much larger than the width of the bay, the conformalmapping of the bay and the semi infinite sea onto upper complex plane provides a solution of the integral equation in closed form. Particular emphasis is placed on the case where the frequency of the incident waves matches the real-part of the natural frequency of the oscillation of the bay. These natural frequencies are complex because of the radiation conditions imposed at the mouth of the bay. It is found that the complex part of these natural frequencies decreases with decreasing width of the bay. Thus the trapping of the waves in narrower bays leads to a strong resonance phenomenon when the frequency of the incident wave is equal to the real part of the natural frequency.
NASA Astrophysics Data System (ADS)
Gilles, Antonin; Gioia, Patrick; Cozot, Rémi; Morin, Luce
2015-09-01
The hybrid point-source/wave-field method is a newly proposed approach for Computer-Generated Hologram (CGH) calculation, based on the slicing of the scene into several depth layers parallel to the hologram plane. The complex wave scattered by each depth layer is then computed using either a wave-field or a point-source approach according to a threshold criterion on the number of points within the layer. Finally, the complex waves scattered by all the depth layers are summed up in order to obtain the final CGH. Although outperforming both point-source and wave-field methods without producing any visible artifact, this approach has not yet been used for animated holograms, and the possible exploitation of temporal redundancies has not been studied. In this paper, we propose a fast computation of video holograms by taking into account those redundancies. Our algorithm consists of three steps. First, intensity and depth data of the current 3D video frame are extracted and compared with those of the previous frame in order to remove temporally redundant data. Then the CGH pattern for this compressed frame is generated using the hybrid point-source/wave-field approach. The resulting CGH pattern is finally transmitted to the video output and stored in the previous frame buffer. Experimental results reveal that our proposed method is able to produce video holograms at interactive rates without producing any visible artifact.
Jiang, Jianfei; Bakan, Ahmet; Kapralov, Alexandr A.; Silva, K. Ishara; Huang, Zhentai; Amoscato, Andrew A.; Peterson, James; Garapati, Venkata Krishna; Saxena, Sunil; Bayir, Hülya; Atkinson, Jeffrey; Bahar, Ivet; Kagan, Valerian E.
2014-01-01
Mitochondria have emerged as the major regulatory platform responsible for coordination of numerous metabolic reactions as well as cell death processes, whereby the execution of intrinsic apoptosis includes the production of reactive oxygen species fueling oxidation of cardiolipin (CL) catalyzed by cytochrome (cyt) c. As this oxidation occurs within the peroxidase complex of cyt c with CL, the latter represents a promising target for the discovery and design of drugs with anti-apoptotic mechanism of action. In this work, we designed and synthesized a new group of mitochondria-targeted imidazole-substituted analogues of stearic acid TPP-n-ISA with different positions of the attached imidazole group on the fatty acid (n=6, 8, 10, 13 and 14). By using a combination of absorption spectroscopy and EPR protocols (continuous wave electron paramagnetic resonance, and electron spin echo envelope modulation) we demonstrated that TPP-n-ISA indeed were able to potently suppress CL induced structural re-arrangements in cyt c paving the way to its peroxidase competence. TPP-n-ISA analogues preserved the low spin hexa-coordinated heme iron state in cyt c/CL complexes whereby TPP-6-ISA displayed a significantly more effective preservation pattern than TPP-14-ISA. Elucidation of these intermolecular stabilization mechanisms of cyt c identified TPP-6-ISA as an effective inhibitor of the peroxidase function of cyt c/CL complexes with a significant anti-apoptotic potential realized in mouse embryonic cells exposed to ionizing irradiation. These experimental findings were detailed and supported by all atom molecular dynamics simulations. Based on the experimental data and computations predictions, we identified TPP-6-ISA as a candidate drug with optimized anti-apoptotic potency. PMID:24631490
Jiang, Jianfei; Bakan, Ahmet; Kapralov, Alexandr A; Silva, K Ishara; Huang, Zhentai; Amoscato, Andrew A; Peterson, James; Garapati, Venkata Krishna; Saxena, Sunil; Bayir, Hülya; Atkinson, Jeffrey; Bahar, Ivet; Kagan, Valerian E
2014-06-01
Mitochondria have emerged as the major regulatory platform responsible for the coordination of numerous metabolic reactions as well as cell death processes, whereby the execution of intrinsic apoptosis includes the production of reactive oxygen species fueling oxidation of cardiolipin (CL) catalyzed by cytochrome (Cyt) c. As this oxidation occurs within the peroxidase complex of Cyt c with CL, the latter represents a promising target for the discovery and design of drugs with antiapoptotic mechanisms of action. In this work, we designed and synthesized a new group of mitochondria-targeted imidazole-substituted analogs of stearic acid TPP-n-ISAs with various positions of the attached imidazole group on the fatty acid (n = 6, 8, 10, 13, and 14). By using a combination of absorption spectroscopy and EPR protocols (continuous wave electron paramagnetic resonance and electron spin echo envelope modulation) we demonstrated that TPP-n-ISAs indeed were able to potently suppress CL-induced structural rearrangements in Cyt c, paving the way to its peroxidase competence. TPP-n-ISA analogs preserved the low-spin hexa-coordinated heme-iron state in Cyt c/CL complexes whereby TPP-6-ISA displayed a significantly more effective preservation pattern than TPP-14-ISA. Elucidation of these intermolecular stabilization mechanisms of Cyt c identified TPP-6-ISA as an effective inhibitor of the peroxidase function of Cyt c/CL complexes with a significant antiapoptotic potential realized in mouse embryonic cells exposed to ionizing irradiation. These experimental findings were detailed and supported by all-atom molecular dynamics simulations. Based on the experimental data and computation predictions, we identified TPP-6-ISA as a candidate drug with optimized antiapoptotic potency. Copyright © 2014 Elsevier Inc. All rights reserved.
Analysis of potential trade-offs in regulation of disinfection by-products
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cromwell, J.E.; Zhang, X.; Regli, S.
1992-11-01
Executive Order 12291 requires the preparation of a Regulatory Impact Analysis (RIA) on all new major federal regulations. The goal of an RIA is to develop and organize information on benefits, costs, and economic impacts so as to clarify trade-offs among alternative regulatory options. This paper outlines explicit methodology for assessing the technical potential for risk-risk tradeoffs. The strategies used to cope with complexities and uncertainties in developing the Disinfection By-Products Regulatory Analysis Model are explained. Results are presented and discussed in light of uncertainties, and in light of the analytical requirements for regulatory impact analysis.
A transcriptional blueprint for a spiral-cleaving embryo.
Chou, Hsien-Chao; Pruitt, Margaret M; Bastin, Benjamin R; Schneider, Stephan Q
2016-08-05
The spiral cleavage mode of early development is utilized in over one-third of all animal phyla and generates embryonic cells of different size, position, and fate through a conserved set of stereotypic and invariant asymmetric cell divisions. Despite the widespread use of spiral cleavage, regulatory and molecular features for any spiral-cleaving embryo are largely uncharted. To address this gap we use RNA-sequencing on the spiralian model Platynereis dumerilii to capture and quantify the first complete genome-wide transcriptional landscape of early spiral cleavage. RNA-sequencing datasets from seven stages in early Platynereis development, from the zygote to the protrochophore, are described here including the de novo assembly and annotation of ~17,200 Platynereis genes. Depth and quality of the RNA-sequencing datasets allow the identification of the temporal onset and level of transcription for each annotated gene, even if the expression is restricted to a single cell. Over 4000 transcripts are maternally contributed and cleared by the end of the early spiral cleavage phase. Small early waves of zygotic expression are followed by major waves of thousands of genes, demarcating the maternal to zygotic transition shortly after the completion of spiral cleavages in this annelid species. Our comprehensive stage-specific transcriptional analysis of early embryonic stages in Platynereis elucidates the regulatory genome during early spiral embryogenesis and defines the maternal to zygotic transition in Platynereis embryos. This transcriptome assembly provides the first systems-level view of the transcriptional and regulatory landscape for a spiral-cleaving embryo.
USDA-ARS?s Scientific Manuscript database
Puberty is a complex physiological event by which animals mature into an adult capable of sexual reproduction. In order to enhance our understanding of the genes and regulatory pathways and networks involved in puberty, we characterized the transcriptome of five reproductive tissues (i.e., hypothal...
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... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-64805; File No. SR-ISE-2011-30] Self-Regulatory Organizations; International Securities Exchange, LLC; Order Approving a Proposed Rule Change Relating to Complex Orders July 5, 2011. I. Introduction On May 23, 2011, the International Securities Exchange, LLC...
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... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-65548; File No. SR-ISE-2011-39] Self-Regulatory Organizations; International Securities Exchange, LLC; Order Approving a Proposed Rule Change Relating to Complex Orders October 13, 2011. I. Introduction On July 1, 2011, the International Securities Exchange...
Eto, Koji; Nishikii, Hidekazu; Ogaeri, Takunori; Suetsugu, Shiro; Kamiya, Akihide; Kobayashi, Toshihiro; Yamazaki, Daisuke; Oda, Atsushi; Takenawa, Tadaomi; Nakauchi, Hiromitsu
2007-11-15
Actin polymerization is crucial in throm-bopoiesis, platelet adhesion, and mega-karyocyte (MK) and platelet spreading. The Wiskott-Aldrich syndrome protein (WASp) homolog WAVE functions downstream of Rac and plays a pivotal role in lamellipodia formation. While MKs and platelets principally express WAVE1 and WAVE2, which are associated with Abi1, the physiologic significance of WAVE isoforms remains undefined. We generated WAVE2(-/-) embryonic stem (ES) cells because WAVE2-null mice die by embryonic day (E) 12.5. We found that while WAVE2(-/-) ES cells differentiated into immature MKs on OP9 stroma, they were severely impaired in terminal differentiation and in platelet production. WAVE2(-/-) MKs exhibited a defect in peripheral lamellipodia on fibrinogen even with phorbol 12-myristate 13-acetate (PMA) costimulation, indicating a requirement of WAVE2 for integrin alpha(IIb)beta(3)-mediated full spreading. MKs in which expression of Abi1 was reduced by small interfering RNA (siRNA) exhibited striking similarity to WAVE2(-/-) MKs in maturation and spreading. Interestingly, the knockdown of IRSp53, a Rac effector that preferentially binds to WAVE2, impaired the development of lamellipodia without affecting proplatelet production. In contrast, thrombopoiesis in vivo and platelet spreading on fibrinogen in vitro were intact in WAVE1-null mice. These observations clarify indispensable roles for the WAVE2/Abi1 complex in alpha(IIb)beta(3)-mediated lamellipodia by MKs and platelets through Rac and IRSp53, and additionally in thrombopoiesis independent of Rac and IRSp53.
NASA Astrophysics Data System (ADS)
Chen, Shuyi S.; Curcic, Milan
2016-07-01
Forecasting hurricane impacts of extreme winds and flooding requires accurate prediction of hurricane structure and storm-induced ocean surface waves days in advance. The waves are complex, especially near landfall when the hurricane winds and water depth varies significantly and the surface waves refract, shoal and dissipate. In this study, we examine the spatial structure, magnitude, and directional spectrum of hurricane-induced ocean waves using a high resolution, fully coupled atmosphere-wave-ocean model and observations. The coupled model predictions of ocean surface waves in Hurricane Ike (2008) over the Gulf of Mexico and Superstorm Sandy (2012) in the northeastern Atlantic and coastal region are evaluated with the NDBC buoy and satellite altimeter observations. Although there are characteristics that are general to ocean waves in both hurricanes as documented in previous studies, wave fields in Ike and Sandy possess unique properties due mostly to the distinct wind fields and coastal bathymetry in the two storms. Several processes are found to significantly modulate hurricane surface waves near landfall. First, the phase speed and group velocities decrease as the waves become shorter and steeper in shallow water, effectively increasing surface roughness and wind stress. Second, the bottom-induced refraction acts to turn the waves toward the coast, increasing the misalignment between the wind and waves. Third, as the hurricane translates over land, the left side of the storm center is characterized by offshore winds over very short fetch, which opposes incoming swell. Landfalling hurricanes produce broader wave spectra overall than that of the open ocean. The front-left quadrant is most complex, where the combination of windsea, swell propagating against the wind, increasing wind-wave stress, and interaction with the coastal topography requires a fully coupled model to meet these challenges in hurricane wave and surge prediction.
The identification of cis-regulatory elements: A review from a machine learning perspective.
Li, Yifeng; Chen, Chih-Yu; Kaye, Alice M; Wasserman, Wyeth W
2015-12-01
The majority of the human genome consists of non-coding regions that have been called junk DNA. However, recent studies have unveiled that these regions contain cis-regulatory elements, such as promoters, enhancers, silencers, insulators, etc. These regulatory elements can play crucial roles in controlling gene expressions in specific cell types, conditions, and developmental stages. Disruption to these regions could contribute to phenotype changes. Precisely identifying regulatory elements is key to deciphering the mechanisms underlying transcriptional regulation. Cis-regulatory events are complex processes that involve chromatin accessibility, transcription factor binding, DNA methylation, histone modifications, and the interactions between them. The development of next-generation sequencing techniques has allowed us to capture these genomic features in depth. Applied analysis of genome sequences for clinical genetics has increased the urgency for detecting these regions. However, the complexity of cis-regulatory events and the deluge of sequencing data require accurate and efficient computational approaches, in particular, machine learning techniques. In this review, we describe machine learning approaches for predicting transcription factor binding sites, enhancers, and promoters, primarily driven by next-generation sequencing data. Data sources are provided in order to facilitate testing of novel methods. The purpose of this review is to attract computational experts and data scientists to advance this field. Crown Copyright © 2015. Published by Elsevier Ireland Ltd. All rights reserved.
Design and performance of heart assist or artificial heart control systems
NASA Technical Reports Server (NTRS)
Webb, J. A., Jr.; Gebben, V. D.
1978-01-01
The factors leading to the design of a controlled driving system for either a heart assist pump or artificial heart are discussed. The system provides square pressure waveform to drive a pneumatic-type blood pump. For assist usage the system uses an R-wave detector circuit that can detect the R-wave of the electrocardiogram in the presence of electrical disturbances. This circuit provides a signal useful for synchronizing an assist pump with the natural heart. It synchronizes a square wave circuit, the output of which is converted into square waveforms of pneumatic pressure suitable for driving both assist device and artificial heart. The pressure levels of the driving waveforms are controlled by means of feedback channels to maintain physiological regulation of the artificial heart's output flow. A more compact system that could achieve similar regulatory characteristics is also discussed.
NASA Astrophysics Data System (ADS)
Smith, J. A.; Peter, D. B.; Tromp, J.; Komatitsch, D.; Lefebvre, M. P.
2015-12-01
We present both SPECFEM3D_Cartesian and SPECFEM3D_GLOBE open-source codes, representing high-performance numerical wave solvers simulating seismic wave propagation for local-, regional-, and global-scale application. These codes are suitable for both forward propagation in complex media and tomographic imaging. Both solvers compute highly accurate seismic wave fields using the continuous Galerkin spectral-element method on unstructured meshes. Lateral variations in compressional- and shear-wave speeds, density, as well as 3D attenuation Q models, topography and fluid-solid coupling are all readily included in both codes. For global simulations, effects due to rotation, ellipticity, the oceans, 3D crustal models, and self-gravitation are additionally included. Both packages provide forward and adjoint functionality suitable for adjoint tomography on high-performance computing architectures. We highlight the most recent release of the global version which includes improved performance, simultaneous MPI runs, OpenCL and CUDA support via an automatic source-to-source transformation library (BOAST), parallel I/O readers and writers for databases using ADIOS and seismograms using the recently developed Adaptable Seismic Data Format (ASDF) with built-in provenance. This makes our spectral-element solvers current state-of-the-art, open-source community codes for high-performance seismic wave propagation on arbitrarily complex 3D models. Together with these solvers, we provide full-waveform inversion tools to image the Earth's interior at unprecedented resolution.
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... Amending NYSE MKT Rule 980NY, To Remove Provisions Governing How the Complex Matching Engine Handles Electronic Complex Orders That Contain a Stock Leg May 30, 2013. Pursuant to Section 19(b)(1)\\1\\ of the... governing how the Complex Matching Engine (``CME'') handles Electronic Complex Orders that contain a stock...
Rostami, Javad; Chen, Jingming; Tse, Peter W
2017-02-07
Ultrasonic guided waves have been extensively applied for non-destructive testing of plate-like structures particularly pipes in past two decades. In this regard, if a structure has a simple geometry, obtained guided waves' signals are easy to explain. However, any small degree of complexity in the geometry such as contacting with other materials may cause an extra amount of complication in the interpretation of guided wave signals. The problem deepens if defects have irregular shapes such as natural corrosion. Signal processing techniques that have been proposed for guided wave signals' analysis are generally good for simple signals obtained in a highly controlled experimental environment. In fact, guided wave signals in a real situation such as the existence of natural corrosion in wall-covered pipes are much more complicated. Considering pipes in residential buildings that pass through concrete walls, in this paper we introduced Smooth Empirical Mode Decomposition (SEMD) to efficiently separate overlapped guided waves. As empirical mode decomposition (EMD) which is a good candidate for analyzing non-stationary signals, suffers from some shortcomings, wavelet transform was adopted in the sifting stage of EMD to improve its outcome in SEMD. However, selection of mother wavelet that suits best for our purpose plays an important role. Since in guided wave inspection, the incident waves are well known and are usually tone-burst signals, we tailored a complex tone-burst signal to be used as our mother wavelet. In the sifting stage of EMD, wavelet de-noising was applied to eliminate unwanted frequency components from each IMF. SEMD greatly enhances the performance of EMD in guided wave analysis for highly contaminated signals. In our experiment on concrete covered pipes with natural corrosion, this method not only separates the concrete wall indication clearly in time domain signal, a natural corrosion with complex geometry that was hidden and located inside the concrete section was successfully exposed.
RELATIVE ACTIN NUCLEATION PROMOTION EFFICIENCY BY WASP AND WAVE PROTEINS IN ENDOTHELIAL CELLS
Kang, Hyeran; Wang, Jingjing; Longley, Sarah J.; Tang, Jay X.; Shaw, Sunil K.
2010-01-01
The mammalian genome encodes multiple WASP1 (Wiskott-Aldrich Syndrome Protein)/WAVE (WASP-family Verprolin homologous) proteins. Members of this family interact with the Arp (actin related protein) 2/3 complex to promote growth of a branched actin network near the plasma membrane or the surface of moving cargos. Arp2/3 mediated branching can further lead to formation of comet tails (actin rockets). Despite their similar domain structure, different WASP/WAVE family members fulfill unique functions that depend on their subcellular location and activity levels. We measured the relative efficiency of actin nucleation promotion of full length WASP/WAVE proteins in a cytoplasmic extract from primary human umbilical vein endothelial cells (HUVEC). In this assay WAVE2 and WAVE3 complexes showed higher nucleation efficiency than WAVE1 and N-WASP, indicating distinct cellular controls for different family members. Previously, WASP and N-WASP were the only members that were known to stimulate comet formation. We observed that in addition to N-WASP, WAVE3 also induced short actin tails, and the other WAVEs induced formation of asymmetric actin shells. Differences in shape and structure of actin-based growth may reflect varying ability of WASP/WAVE proteins to break symmetry of the actin shell, possibly by differential recruitment of actin bundling or severing (pruning or debranching) factors. PMID:20816932
Tandem Affinity Purification of Protein Complexes from Eukaryotic Cells.
Ma, Zheng; Fung, Victor; D'Orso, Iván
2017-01-26
The purification of active protein-protein and protein-nucleic acid complexes is crucial for the characterization of enzymatic activities and de novo identification of novel subunits and post-translational modifications. Bacterial systems allow for the expression and purification of a wide variety of single polypeptides and protein complexes. However, this system does not enable the purification of protein subunits that contain post-translational modifications (e.g., phosphorylation and acetylation), and the identification of novel regulatory subunits that are only present/expressed in the eukaryotic system. Here, we provide a detailed description of a novel, robust, and efficient tandem affinity purification (TAP) method using STREP- and FLAG-tagged proteins that facilitates the purification of protein complexes with transiently or stably expressed epitope-tagged proteins from eukaryotic cells. This protocol can be applied to characterize protein complex functionality, to discover post-translational modifications on complex subunits, and to identify novel regulatory complex components by mass spectrometry. Notably, this TAP method can be applied to study protein complexes formed by eukaryotic or pathogenic (viral and bacterial) components, thus yielding a wide array of downstream experimental opportunities. We propose that researchers working with protein complexes could utilize this approach in many different ways.
Ondondo, Beatrice Omusiro
2014-01-01
Excessive immune responses directed against foreign pathogens, self-antigens, or commensal microflora can cause cancer establishment and progression if the execution of tight immuno-regulatory mechanisms fails. On the other hand, induction of potent tumor antigen-specific immune responses together with stimulation of the innate immune system is a pre-requisite for effective anti-tumor immunity, and if suppressed by the strong immuno-regulatory mechanisms can lead to cancer progression. Therefore, it is crucial that the inevitable co-existence of these fundamental, yet conflicting roles of immune-regulatory cells is carefully streamlined as imbalances can be detrimental to the host. Infection with chronic persistent viruses is characterized by severe immune dysfunction resulting in T cell exhaustion and sometimes deletion of antigen-specific T cells. More often, this is due to increased immuno-regulatory processes, which are triggered to down-regulate immune responses and limit immunopathology. However, such heightened levels of immune disruption cause a concomitant loss of tumor immune-surveillance and create a permissive microenvironment for cancer establishment and progression, as demonstrated by increased incidences of cancer in immunosuppressed hosts. Paradoxically, while some cancers arise as a consequence of increased immuno-regulatory mechanisms that inhibit protective immune responses and impinge on tumor surveillance, other cancers arise due to impaired immuno-regulatory mechanisms and failure to limit pathogenic inflammatory responses. This intricate complexity, where immuno-regulatory cells can be beneficial in certain immune settings but detrimental in other settings underscores the need for carefully formulated interventions to equilibrate the balance between immuno-stimulatory and immuno-regulatory processes. PMID:24639678
NASA Astrophysics Data System (ADS)
Jiang, T.; Yue, Y.
2017-12-01
It is well known that the mono-frequency directional seismic wave technology can concentrate seismic waves into a beam. However, little work on the method and effect of variable frequency directional seismic wave under complex geological conditions have been done .We studied the variable frequency directional wave theory in several aspects. Firstly, we studied the relation between directional parameters and the direction of the main beam. Secondly, we analyzed the parameters that affect the beam width of main beam significantly, such as spacing of vibrator, wavelet dominant frequency, and number of vibrator. In addition, we will study different characteristics of variable frequency directional seismic wave in typical velocity models. In order to examine the propagation characteristics of directional seismic wave, we designed appropriate parameters according to the character of direction parameters, which is capable to enhance the energy of the main beam direction. Further study on directional seismic wave was discussed in the viewpoint of power spectral. The results indicate that the energy intensity of main beam direction increased 2 to 6 times for a multi-ore body velocity model. It showed us that the variable frequency directional seismic technology provided an effective way to strengthen the target signals under complex geological conditions. For concave interface model, we introduced complicated directional seismic technology which supports multiple main beams to obtain high quality data. Finally, we applied the 9-element variable frequency directional seismic wave technology to process the raw data acquired in a oil-shale exploration area. The results show that the depth of exploration increased 4 times with directional seismic wave method. Based on the above analysis, we draw the conclusion that the variable frequency directional seismic wave technology can improve the target signals of different geologic conditions and increase exploration depth with little cost. Due to inconvenience of hydraulic vibrators in complicated surface area, we suggest that the combination of high frequency portable vibrator and variable frequency directional seismic wave method is an alternative technology to increase depth of exploration or prospecting.
Wave reflection in a reaction-diffusion system: breathing patterns and attenuation of the echo.
Tsyganov, M A; Ivanitsky, G R; Zemskov, E P
2014-05-01
Formation and interaction of the one-dimensional excitation waves in a reaction-diffusion system with the piecewise linear reaction functions of the Tonnelier-Gerstner type are studied. We show that there exists a parameter region where the established regime of wave propagation depends on initial conditions. Wave phenomena with a complex behavior are found: (i) the reflection of waves at a growing distance (the remote reflection) upon their collision with each other or with no-flux boundaries and (ii) the periodic transformation of waves with the jumping from one regime of wave propagation to another (the periodic trigger wave).
Wave reflection in a reaction-diffusion system: Breathing patterns and attenuation of the echo
NASA Astrophysics Data System (ADS)
Tsyganov, M. A.; Ivanitsky, G. R.; Zemskov, E. P.
2014-05-01
Formation and interaction of the one-dimensional excitation waves in a reaction-diffusion system with the piecewise linear reaction functions of the Tonnelier-Gerstner type are studied. We show that there exists a parameter region where the established regime of wave propagation depends on initial conditions. Wave phenomena with a complex behavior are found: (i) the reflection of waves at a growing distance (the remote reflection) upon their collision with each other or with no-flux boundaries and (ii) the periodic transformation of waves with the jumping from one regime of wave propagation to another (the periodic trigger wave).
Weidmann, Chase A; Qiu, Chen; Arvola, René M; Lou, Tzu-Fang; Killingsworth, Jordan; Campbell, Zachary T; Tanaka Hall, Traci M; Goldstrohm, Aaron C
2016-01-01
Collaboration among the multitude of RNA-binding proteins (RBPs) is ubiquitous, yet our understanding of these key regulatory complexes has been limited to single RBPs. We investigated combinatorial translational regulation by Drosophila Pumilio (Pum) and Nanos (Nos), which control development, fertility, and neuronal functions. Our results show how the specificity of one RBP (Pum) is modulated by cooperative RNA recognition with a second RBP (Nos) to synergistically repress mRNAs. Crystal structures of Nos-Pum-RNA complexes reveal that Nos embraces Pum and RNA, contributes sequence-specific contacts, and increases Pum RNA-binding affinity. Nos shifts the recognition sequence and promotes repression complex formation on mRNAs that are not stably bound by Pum alone, explaining the preponderance of sub-optimal Pum sites regulated in vivo. Our results illuminate the molecular mechanism of a regulatory switch controlling crucial gene expression programs, and provide a framework for understanding how the partnering of RBPs evokes changes in binding specificity that underlie regulatory network dynamics. DOI: http://dx.doi.org/10.7554/eLife.17096.001 PMID:27482653
Weidmann, Chase A.; Qiu, Chen; Arvola, René M.; ...
2016-08-02
Collaboration among the multitude of RNA-binding proteins (RBPs) is ubiquitous, yet our understanding of these key regulatory complexes has been limited to single RBPs. We investigated combinatorial translational regulation by Drosophila Pumilio (Pum) and Nanos (Nos), which control development, fertility, and neuronal functions. Our results show how the specificity of one RBP (Pum) is modulated by cooperative RNA recognition with a second RBP (Nos) to synergistically repress mRNAs. Crystal structures of Nos-Pum-RNA complexes reveal that Nos embraces Pum and RNA, contributes sequence-specific contacts, and increases Pum RNA-binding affinity. Nos shifts the recognition sequence and promotes repression complex formation on mRNAsmore » that are not stably bound by Pum alone, explaining the preponderance of sub-optimal Pum sites regulated in vivo. Our results illuminate the molecular mechanism of a regulatory switch controlling crucial gene expression programs, and provide a framework for understanding how the partnering of RBPs evokes changes in binding specificity that underlie regulatory network dynamics.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Weidmann, Chase A.; Qiu, Chen; Arvola, René M.
Collaboration among the multitude of RNA-binding proteins (RBPs) is ubiquitous, yet our understanding of these key regulatory complexes has been limited to single RBPs. We investigated combinatorial translational regulation by Drosophila Pumilio (Pum) and Nanos (Nos), which control development, fertility, and neuronal functions. Our results show how the specificity of one RBP (Pum) is modulated by cooperative RNA recognition with a second RBP (Nos) to synergistically repress mRNAs. Crystal structures of Nos-Pum-RNA complexes reveal that Nos embraces Pum and RNA, contributes sequence-specific contacts, and increases Pum RNA-binding affinity. Nos shifts the recognition sequence and promotes repression complex formation on mRNAsmore » that are not stably bound by Pum alone, explaining the preponderance of sub-optimal Pum sites regulated in vivo. Our results illuminate the molecular mechanism of a regulatory switch controlling crucial gene expression programs, and provide a framework for understanding how the partnering of RBPs evokes changes in binding specificity that underlie regulatory network dynamics.« less
Healthy coral reefs may assure coastal protection in face of climate change related sea level rise
NASA Astrophysics Data System (ADS)
Harris, D. L.; Rovere, A.; Parravicini, V.; Casella, E.; Canavesio, R.; Collin, A.
2016-12-01
Coral reefs are diverse ecosystems that support millions of people worldwide providing crucial services, of which, coastal protection is one of the most relevant. The efficiency of coral reefs in protecting coastlines and dissipating waves is directly linked to the cover of living corals and three dimensional reef structural complexity. Climate change and human impacts are leading to severe global reductions in live coral cover, posing serious concerns regarding the capacity of degraded reef systems in protecting tropical coastal regions. Although it is known that the loss of structurally complex reefs may lead to greater erosion of coastlines, this process has rarely been quantified and it is still unknown whether the maintenance of healthy reefs through conservation will be enough to guarantee coastal protection during rising sea levels. We show that a significant loss of wave dissipation and a subsequent increase in back-reef wave height (up to 5 times present wave height) could occur even at present sea level if living corals are lost and reef structural complexity is reduced. Yet we also show that healthy reefs, measured by structural complexity and efficiency of vertical reef accretion, may maintain their present capacity of wave dissipation even under rising sea levels. Our results indicate that the health of coral reefs and not sea level rise will be the major determinant of the coastal protection services provided by coral reefs and calls for investments into coral reef conservation to ensure the future protection of tropical coastal communities.
Dynamics of nonautonomous rogue waves in Bose-Einstein condensate
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhao, Li-Chen, E-mail: zhaolichen3@163.com
2013-02-15
We study rogue waves of Bose-Einstein condensate (BEC) analytically in a time-dependent harmonic trap with a complex potential. Properties of the nonautonomous rogue waves are investigated analytically. It is reported that there are possibilities to 'catch' rogue waves through manipulating nonlinear interaction properly. The results provide many possibilities to manipulate rogue waves experimentally in a BEC system. - Highlights: Black-Right-Pointing-Pointer One more generalized rogue wave solutions are presented. Black-Right-Pointing-Pointer Present one possible way to catch a rouge wave. Black-Right-Pointing-Pointer Properties of rogue waves are investigated analytically for the first time. Black-Right-Pointing-Pointer Provide many possibilities to manipulate rogue waves in BEC.
Kang, Jin-Ho; Campos, Marcelo L.; Zemelis-Durfee, Starla; ...
2016-07-31
Trichomes are epidermal structures that provide a first line of defense against arthropod herbivores. The recessive hairless (hl) mutation in tomato (Solanum lycopersicum L.) causes severe distortion of trichomes on all aerial tissues, impairs the accumulation of sesquiterpene and polyphenolic compounds in glandular trichomes, and compromises resistance to the specialist herbivore Manduca sexta. Here, we demonstrate that the tomato Hl gene encodes a subunit (SRA1) of the highly conserved WAVE regulatory complex that controls nucleation of actin filaments in a wide range of eukaryotic cells. The tomato SRA1 gene spans a 42-kb region containing both Solyc11g013280 and Solyc11g013290. The hlmore » mutation corresponds to a complex 3-kb deletion that removes the last exon of the gene. Expression of a wild-type SRA1 cDNA in the hl mutant background restored normal trichome development, accumulation of glandular trichomederived metabolites, and resistance to insect herbivory. These findings thus establish a role for SRA1 in the development of tomato trichomes and also implicate the actin-cytoskeleton network in cytosolic control of specialized metabolism for plant defense. We also show that the brittleness of hl mutant stems is associated with altered mechanical and cell morphological properties of stem tissue, and demonstrate that this defect is directly linked to the mutation in SRA1.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kang, Jin-Ho; Campos, Marcelo L.; Zemelis-Durfee, Starla
Trichomes are epidermal structures that provide a first line of defense against arthropod herbivores. The recessive hairless (hl) mutation in tomato (Solanum lycopersicum L.) causes severe distortion of trichomes on all aerial tissues, impairs the accumulation of sesquiterpene and polyphenolic compounds in glandular trichomes, and compromises resistance to the specialist herbivore Manduca sexta. Here, we demonstrate that the tomato Hl gene encodes a subunit (SRA1) of the highly conserved WAVE regulatory complex that controls nucleation of actin filaments in a wide range of eukaryotic cells. The tomato SRA1 gene spans a 42-kb region containing both Solyc11g013280 and Solyc11g013290. The hlmore » mutation corresponds to a complex 3-kb deletion that removes the last exon of the gene. Expression of a wild-type SRA1 cDNA in the hl mutant background restored normal trichome development, accumulation of glandular trichomederived metabolites, and resistance to insect herbivory. These findings thus establish a role for SRA1 in the development of tomato trichomes and also implicate the actin-cytoskeleton network in cytosolic control of specialized metabolism for plant defense. We also show that the brittleness of hl mutant stems is associated with altered mechanical and cell morphological properties of stem tissue, and demonstrate that this defect is directly linked to the mutation in SRA1.« less
Turing-like structures in a functional model of cortical spreading depression
NASA Astrophysics Data System (ADS)
Verisokin, A. Yu.; Verveyko, D. V.; Postnov, D. E.
2017-12-01
Cortical spreading depression (CSD) along with migraine waves and spreading depolarization events with stroke or injures are the front-line examples of extreme physiological behaviors of the brain cortex which manifest themselves via the onset and spreading of localized areas of neuronal hyperactivity followed by their depression. While much is known about the physiological pathways involved, the dynamical mechanisms of the formation and evolution of complex spatiotemporal patterns during CSD are still poorly understood, in spite of the number of modeling studies that have been already performed. Recently we have proposed a relatively simple mathematical model of cortical spreading depression which counts the effects of neurovascular coupling and cerebral blood flow redistribution during CSD. In the present study, we address the main dynamical consequences of newly included pathways, namely, the changes in the formation and propagation speed of the CSD front and the pattern formation features in two dimensions. Our most notable finding is that the combination of vascular-mediated spatial coupling with local regulatory mechanisms results in the formation of stationary Turing-like patterns during a CSD event.
Federal Register 2010, 2011, 2012, 2013, 2014
2013-03-19
...-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and Immediate Effectiveness of a Proposed Rule Change Relating to Complex Orders and Mini-Options March 13, 2013. Pursuant to...\\ notice is hereby given that on March 7, 2013, Chicago Board Options Exchange, Incorporated (the...
In the Eyes of Others: Monitoring for Relational Value Cues
ERIC Educational Resources Information Center
Tyler, James M.
2008-01-01
It was hypothesized that monitoring the social environment for relational value (RV) cues both consumes and depletes self-regulatory resources. Consistent with predictions, the results suggest that regulatory resources are depleted when people monitor for relational cues (Experiments 1 and 2), that the capacity to monitor for complex (vs. simple)…
USDA-ARS?s Scientific Manuscript database
Forty crossbred beef steers were used to determine the effects metabolizable energy (ME) intake and of site and complexity of carbohydrate (CHO) infusion on expression of genes encoding lipogenic enzymes and regulatory proteins in subcutaneous (SC), mesenteric (MES) and omental (OM) adipose. Treatm...
Biomechanical cell regulatory networks as complex adaptive systems in relation to cancer.
Feller, Liviu; Khammissa, Razia Abdool Gafaar; Lemmer, Johan
2017-01-01
Physiological structure and function of cells are maintained by ongoing complex dynamic adaptive processes in the intracellular molecular pathways controlling the overall profile of gene expression, and by genes in cellular gene regulatory circuits. Cytogenetic mutations and non-genetic factors such as chronic inflammation or repetitive trauma, intrinsic mechanical stresses within extracellular matrix may induce redirection of gene regulatory circuits with abnormal reactivation of embryonic developmental programmes which can now drive cell transformation and cancer initiation, and later cancer progression and metastasis. Some of the non-genetic factors that may also favour cancerization are dysregulation in epithelial-mesenchymal interactions, in cell-to-cell communication, in extracellular matrix turnover, in extracellular matrix-to-cell interactions and in mechanotransduction pathways. Persistent increase in extracellular matrix stiffness, for whatever reason, has been shown to play an important role in cell transformation, and later in cancer cell invasion. In this article we review certain cell regulatory networks driving carcinogenesis, focussing on the role of mechanical stresses modulating structure and function of cells and their extracellular matrices.
Evaluation of quasi-square wave inverter as a power source for induction motors
NASA Technical Reports Server (NTRS)
Guynes, B. V.; Haggard, R. L.; Lanier, J. R., Jr.
1977-01-01
The relative merits of quasi-square wave inverter-motor technology versus a sine wave inverter-motor system were investigated. The empirical results of several tests on various sizes of wye-wound induction motors are presented with mathematical analysis to support the conclusions of the study. It was concluded that, within the limitations presented, the quasi-square wave inverter-motor system is superior to the more complex sine wave system for most induction motor applications in space.
The ribonucleoprotein Csr network.
Seyll, Ethel; Van Melderen, Laurence
2013-11-08
Ribonucleoprotein complexes are essential regulatory components in bacteria. In this review, we focus on the carbon storage regulator (Csr) network, which is well conserved in the bacterial world. This regulatory network is composed of the CsrA master regulator, its targets and regulators. CsrA binds to mRNA targets and regulates translation either negatively or positively. Binding to small non-coding RNAs controls activity of this protein. Expression of these regulators is tightly regulated at the level of transcription and stability by various global regulators (RNAses, two-component systems, alarmone). We discuss the implications of these complex regulations in bacterial adaptation.
Cross-β Polymerization of Low Complexity Sequence Domains.
Kato, Masato; McKnight, Steven L
2017-03-01
Most transcription factors and RNA regulatory proteins encoded by eukaryotic genomes ranging from yeast to humans contain polypeptide domains variously described as intrinsically disordered, prion-like, or of low complexity (LC). These LC domains exist in an unfolded state when DNA and RNA regulatory proteins are studied in biochemical isolation from cells. Upon incubation in the purified state, many of these LC domains polymerize into homogeneous, labile amyloid-like fibers. Here, we consider several lines of evidence that may favor biologic utility for LC domain polymers. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.
Regulation of microtubule nucleation mediated by γ-tubulin complexes.
Sulimenko, Vadym; Hájková, Zuzana; Klebanovych, Anastasiya; Dráber, Pavel
2017-05-01
The microtubule cytoskeleton is critically important for spatio-temporal organization of eukaryotic cells. The nucleation of new microtubules is typically restricted to microtubule organizing centers (MTOCs) and requires γ-tubulin that assembles into multisubunit complexes of various sizes. γ-Tubulin ring complexes (TuRCs) are efficient microtubule nucleators and are associated with large number of targeting, activating and modulating proteins. γ-Tubulin-dependent nucleation of microtubules occurs both from canonical MTOCs, such as spindle pole bodies and centrosomes, and additional sites such as Golgi apparatus, nuclear envelope, plasma membrane-associated sites, chromatin and surface of pre-existing microtubules. Despite many advances in structure of γ-tubulin complexes and characterization of γTuRC interacting factors, regulatory mechanisms of microtubule nucleation are not fully understood. Here, we review recent work on the factors and regulatory mechanisms that are involved in centrosomal and non-centrosomal microtubule nucleation.
Evaluation of genetic and metabolic role of SKIP11 in Arabidopsis thaliana
NASA Astrophysics Data System (ADS)
Hassan, Muhammad Naeem ul; Ismail, Ismanizan
2015-09-01
Most of the regulatory proteins are degraded by 26S proteasome complex, only when they are tagged by Ubiquitin. A complex of four proteins, SKP1-Cullin-Ring box-F box (SCF) catalyses the final step to link the Ubiquitin tag with the target proteins. SCF complex interacts with the target proteins through F-box proteins, which confer the overall substrate specificity to the complex. F-box proteins, one of the largest family of proteins in plants have an N-terminal F-box domain and variable C-terminal domains, like leucine-rich repeat, WD-40 repeat and the kelch-repeat domains. In this study, we analysed the role of SKIP11, a kelch containing F-box protein (KFB) from Arabidopsis thaliana, by using reverse genetics strategy. The results show that SKIP11 is involved in the down-regulation of oxylipin pathway, possibly through the degradation of enzymes or/ and the regulatory factors of the pathway.
Savard, Martin; Irani, Sarosh R; Guillemette, Annie; Gosselin-Lefebvre, Stéphanie; Geschwind, Michael; Jansen, Gerard H; Gould, Peter V; Laforce, Robert
2016-02-01
Voltage-gated potassium channel-complex antibodies (VGKC-cAbs) encephalitis, a treatable autoantibody encephalopathy, has been previously reported to clinically mimic sporadic Creutzfeldt-Jakob disease. Among available clinical clues to distinguish them, periodic sharp wave complexes, a typical finding in sporadic Creutzfeldt-Jakob disease, have never been reported in association with VGKC-cAbs encephalitis. A 76-year-old man was transferred to a tertiary neurology center with a clinical history of 6-month weight loss, cognitive disturbance, and nonspecific generalized weakness. He had two seizures the month before transfer and then evolved to severe encephalopathy, requiring mechanical ventilation. Periodic sharp wave complexes every 1 to 2 seconds over slowed background were found on EEG, and MRI showed cerebellar and bifrontal cortical T2/FLAIR/DWI hypersignal without restricted diffusion on ADC mapping. Pancorporal positron emission tomography scan was negative. An immunotherapy trial did not improve the patient condition. Therefore, he died after life support withdrawal. Brain autopsy revealed mononuclear neocortex infiltrate without significant spongiosis, and the anti-VGKC test showed a seropositivity of 336 pmol/L (normal, 0-31), 3 month after the patient deceased. This is the first reported case of VGKC-cAbs encephalitis associated with periodic sharp wave complexes on EEG, which further confuse the differential diagnosis with sporadic Creutzfeldt-Jakob disease. However, the cortical DWI hypersignal without restriction seems to remain a way to discriminate these two entities appropriately, when present. These clues are of paramount importance because VGKC-cAbs encephalitis is a treatable disease.
NASA Astrophysics Data System (ADS)
Hindman, Bradley W.; Jain, Rekha
2018-05-01
The arched field lines forming coronal arcades are often observed to undulate as magnetohydrodynamic waves propagate both across and along the magnetic field. These waves are most likely a combination of resonantly coupled fast magnetoacoustic waves and Alfvén waves. The coupling results in resonant absorption of the fast waves, converting fast wave energy into Alfvén waves. The fast eigenmodes of the arcade have proven difficult to compute or derive analytically, largely because of the mathematical complexity that the coupling introduces. When a traditional spectral decomposition is employed, the discrete spectrum associated with the fast eigenmodes is often subsumed into the continuous Alfvén spectrum. Thus fast eigenmodes become collective modes or quasi-modes. Here we present a spectral decomposition that treats the eigenmodes as having real frequencies but complex wavenumbers. Using this procedure we derive dispersion relations, spatial damping rates, and eigenfunctions for the resonant, fast eigenmodes of the arcade. We demonstrate that resonant absorption introduces a fast mode that would not exist otherwise. This new mode is heavily damped by resonant absorption, travelling only a few wavelengths before losing most of its energy.
Modeling Water Waves with Smoothed Particle Hydrodynamics
2011-09-30
Lagrangian nature of SPH allows the modeling of wave breaking, surf zones, ship waves, and wave-structure interaction, where the free surface becomes...particle detection--To study free surface flows and analyze their complex deformations, we need to know which particles are located on the free surface ...Hydrodynamics is proving to be a competent modeling scheme for free surface flows in two and three dimensions. As the GPU hardware improves, it is
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sang, Yuanrui; Karayaka, H. Bora; Yan, Yanjun
The slider crank is a proven mechanical linkage system with a long history of successful applications, and the slider-crank ocean wave energy converter (WEC) is a type of WEC that converts linear motion into rotation. This paper presents a control algorithm for a slider-crank WEC. In this study, a time-domain hydrodynamic analysis is adopted, and an AC synchronous machine is used in the power take-off system to achieve relatively high system performance. Also, a rule-based phase control strategy is applied to maximize energy extraction, making the system suitable for not only regular sinusoidal waves but also irregular waves. Simulations aremore » carried out under regular sinusoidal wave and synthetically produced irregular wave conditions; performance validations are also presented with high-precision, real ocean wave surface elevation data. The influences of significant wave height, and peak period upon energy extraction of the system are studied. Energy extraction results using the proposed method are compared to those of the passive loading and complex conjugate control strategies; results show that the level of energy extraction is between those of the passive loading and complex conjugate control strategies, and the suboptimal nature of this control strategy is verified.« less
Group Velocity for Leaky Waves
NASA Astrophysics Data System (ADS)
Rzeznik, Andrew; Chumakova, Lyubov; Rosales, Rodolfo
2017-11-01
In many linear dispersive/conservative wave problems one considers solutions in an infinite medium which is uniform everywhere except for a bounded region. In general, localized inhomogeneities of the medium cause partial internal reflection, and some waves leak out of the domain. Often one only desires the solution in the inhomogeneous region, with the exterior accounted for by radiation boundary conditions. Formulating such conditions requires definition of the direction of energy propagation for leaky waves in multiple dimensions. In uniform media such waves have the form exp (d . x + st) where d and s are complex and related by a dispersion relation. A complex s is required since these waves decay via radiation to infinity, even though the medium is conservative. We present a modified form of Whitham's Averaged Lagrangian Theory along with modulation theory to extend the classical idea of group velocity to leaky waves. This allows for solving on the bounded region by representing the waves as a linear combination of leaky modes, each exponentially decaying in time. This presentation is part of a joint project, and applications of these results to example GFD problems will be presented by L. Chumakova in the talk ``Leaky GFD Problems''. This work is partially supported by NSF Grants DMS-1614043, DMS-1719637, and 1122374, and by the Hertz Foundation.
Cross-Modulated Amplitudes and Frequencies Characterize Interacting Components in Complex Systems
NASA Astrophysics Data System (ADS)
Gans, Fabian; Schumann, Aicko Y.; Kantelhardt, Jan W.; Penzel, Thomas; Fietze, Ingo
2009-03-01
The dynamics of complex systems is characterized by oscillatory components on many time scales. To study the interactions between these components we analyze the cross modulation of their instantaneous amplitudes and frequencies, separating synchronous and antisynchronous modulation. We apply our novel technique to brain-wave oscillations in the human electroencephalogram and show that interactions between the α wave and the δ or β wave oscillators as well as spatial interactions can be quantified and related with physiological conditions (e.g., sleep stages). Our approach overcomes the limitation to oscillations with similar frequencies and enables us to quantify directly nonlinear effects such as positive or negative frequency modulation.
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... participants that add or remove liquidity in the Complex Order Book (``maker/taker fees'') in symbols that are... liquidity on the Complex Order Book and $0.30 per contract ($0.32 per contract in the Select Symbols) for taking liquidity from the Complex Order Book. ISE market makers who take liquidity from the Complex Order...
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... Electronic Complex Orders entered to the NYSE Arca System must comply with the order exposure requirements of... Complex Order, a Stock/ Option Order, or a Stock/Complex Order must be entered into the NYSE Arca System... Change Amending NYSE Arca Options Rule 6.62(h) to Define Stock/Complex Orders, Amending NYSE Arca Options...
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... Change Related to the Opening of the Complex Order Book February 6, 2013. Pursuant to Section 19(b)(1) of... complex orders are currently processed through the Exchange's complex order book (``COB'') when the COB... individual orders and quotes in the electronic book or other complex orders in the COB, execute or cancel if...
Murteira, Susana; Millier, Aurélie; Ghezaiel, Zied; Lamure, Michel
2014-01-01
Background Repurposing has become a mainstream strategy in drug development, but it faces multiple challenges, amongst them the increasing and ever changing regulatory framework. This is the second study of a series of three-part publication project with the ultimate goal of understanding the market access rationale and conditions attributed to drug repurposing in the United States and in Europe. The aim of the current study to evaluate the regulatory path associated with each type of repurposing strategy according to the previously proposed nomenclature in the first article of this series. Methods From the cases identified, a selection process retrieved a total of 141 case studies in all countries, harmonized for data availability and common approval in the United States and in Europe. Regulatory information for each original and repurposed drug product was extracted, and several related regulatory attributes were also extracted such as, designation change and filing before or after patent expiry, among others. Descriptive analyses were conducted to determine trends and to investigate potential associations between the different regulatory paths and attributes of interest, for reformulation and repositioning cases separately. Results Within the studied European countries, most of the applications for reformulated products were filed through national applications. In contrast, for repositioned products, the centralized procedure was the most frequent regulatory pathway. Most of the repurposing cases were approved before patent expiry, and those cases have followed more complex regulatory pathways in the United States and in Europe. For new molecular entities filed in the United States, a similar number of cases were developed by serendipity and by a hypothesis-driven approach. However, for the new indication's regulatory pathway in the United States, most of the cases were developed through a hypothesis-driven approach. Conclusion The regulations in the United States and in Europe for drug repositionings and reformulations allowed confirming that repositioning strategies were usually filed under a more complex regulatory process than reformulations. Also, it seems that parameters such as patent expiry and type of repositioning approach or reformulation affect the regulatory pathways chosen for each case. PMID:27226839
Synchronization of calcium waves by mitochondrial substrates in Xenopus laevis oocytes
NASA Astrophysics Data System (ADS)
Jouaville, Laurence S.; Ichas, François; Holmuhamedov, Ekhson L.; Camacho, Patricia; Lechleiter, James D.
1995-10-01
INXenopus oocytes, as well as other cells, inositol-l,4,5-tris-phosphate (Ins(l,4,5)P3)-induced Ca2+ release1-4 is an excitable process that generates propagating Ca2+ waves5-7 that annihilate upon collision8-12. The fundamental property responsible for excitability13 appears to be the Ca2+ dependency of the Ins(l,4,5)P3 receptor9. Here we report that Ins(l,4,5)P3-induced Ca2+ wave activity is strengthened by oxidizable substrates that energize mitochondria, increasing Ca2+ wave amplitude, velocity and interwave period. The effects of pyruvate/malate are blocked by ruthenium red at the Ca2+ uniporter, by rotenone at complex I, and by antimycin A at complex III, and are subsequently rescued at complex IV by ascorbate tetramethylphenylenediamine (TMPD)14. Our data reveal that potential-driven mitochondrial Ca2+ uptake is a major factor in the regulation of Ins(l,4,5)P3-induced Ca2+ release and clearly demonstrate a physiological role of mitochondria in intracellular Ca2+ signalling.
Modulating EGFR Signaling by Targeting the Deacetylase HDAC6-Hsp90 Complex in Breast Tumors
2007-06-01
concomitant increase in 4 directed cell migration (15). Analysis of fibroblasts derived from WAVE2 knockout mice 5 demonstrates deficiency in ruffle...Takenawa. 2003. Differential 1 roles of WAVE1 and WAVE2 in dorsal and peripheral ruffle formation for 2 fibroblast cell migration. Dev Cell 5:595
2011-01-01
Background Green plant leaves have always fascinated biologists as hosts for photosynthesis and providers of basic energy to many food webs. Today, comprehensive databases of gene expression data enable us to apply increasingly more advanced computational methods for reverse-engineering the regulatory network of leaves, and to begin to understand the gene interactions underlying complex emergent properties related to stress-response and development. These new systems biology methods are now also being applied to organisms such as Populus, a woody perennial tree, in order to understand the specific characteristics of these species. Results We present a systems biology model of the regulatory network of Populus leaves. The network is reverse-engineered from promoter information and expression profiles of leaf-specific genes measured over a large set of conditions related to stress and developmental. The network model incorporates interactions between regulators, such as synergistic and competitive relationships, by evaluating increasingly more complex regulatory mechanisms, and is therefore able to identify new regulators of leaf development not found by traditional genomics methods based on pair-wise expression similarity. The approach is shown to explain available gene function information and to provide robust prediction of expression levels in new data. We also use the predictive capability of the model to identify condition-specific regulation as well as conserved regulation between Populus and Arabidopsis. Conclusions We outline a computationally inferred model of the regulatory network of Populus leaves, and show how treating genes as interacting, rather than individual, entities identifies new regulators compared to traditional genomics analysis. Although systems biology models should be used with care considering the complexity of regulatory programs and the limitations of current genomics data, methods describing interactions can provide hypotheses about the underlying cause of emergent properties and are needed if we are to identify target genes other than those constituting the "low hanging fruit" of genomic analysis. PMID:21232107
McBride, David J.; Buckle, Adam; van Heyningen, Veronica; Kleinjan, Dirk A.
2011-01-01
The PAX6 gene plays a crucial role in development of the eye, brain, olfactory system and endocrine pancreas. Consistent with its pleiotropic role the gene exhibits a complex developmental expression pattern which is subject to strict spatial, temporal and quantitative regulation. Control of expression depends on a large array of cis-elements residing in an extended genomic domain around the coding region of the gene. The minimal essential region required for proper regulation of this complex locus has been defined through analysis of human aniridia-associated breakpoints and YAC transgenic rescue studies of the mouse smalleye mutant. We have carried out a systematic DNase I hypersensitive site (HS) analysis across 200 kb of this critical region of mouse chromosome 2E3 to identify putative regulatory elements. Mapping the identified HSs onto a percent identity plot (PIP) shows many HSs correspond to recognisable genomic features such as evolutionarily conserved sequences, CpG islands and retrotransposon derived repeats. We then focussed on a region previously shown to contain essential long range cis-regulatory information, the Pax6 downstream regulatory region (DRR), allowing comparison of mouse HS data with previous human HS data for this region. Reporter transgenic mice for two of the HS sites, HS5 and HS6, show that they function as tissue specific regulatory elements. In addition we have characterised enhancer activity of an ultra-conserved cis-regulatory region located near Pax6, termed E60. All three cis-elements exhibit multiple spatio-temporal activities in the embryo that overlap between themselves and other elements in the locus. Using a deletion set of YAC reporter transgenic mice we demonstrate functional interdependence of the elements. Finally, we use the HS6 enhancer as a marker for the migration of precerebellar neuro-epithelium cells to the hindbrain precerebellar nuclei along the posterior and anterior extramural streams allowing visualisation of migratory defects in both pathways in Pax6Sey/Sey mice. PMID:22220192
NASA Astrophysics Data System (ADS)
Brandt, C.; Thakur, S. C.; Tynan, G. R.
2016-04-01
Complexities of flow patterns in the azimuthal cross-section of a cylindrical magnetized helicon plasma and the corresponding plasma dynamics are investigated by means of a novel scheme for time delay estimation velocimetry. The advantage of this introduced method is the capability of calculating the time-averaged 2D velocity fields of propagating wave-like structures and patterns in complex spatiotemporal data. It is able to distinguish and visualize the details of simultaneously present superimposed entangled dynamics and it can be applied to fluid-like systems exhibiting frequently repeating patterns (e.g., waves in plasmas, waves in fluids, dynamics in planetary atmospheres, etc.). The velocity calculations are based on time delay estimation obtained from cross-phase analysis of time series. Each velocity vector is unambiguously calculated from three time series measured at three different non-collinear spatial points. This method, when applied to fast imaging, has been crucial to understand the rich plasma dynamics in the azimuthal cross-section of a cylindrical linear magnetized helicon plasma. The capabilities and the limitations of this velocimetry method are discussed and demonstrated for two completely different plasma regimes, i.e., for quasi-coherent wave dynamics and for complex broadband wave dynamics involving simultaneously present multiple instabilities.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Brandt, C.; Max-Planck-Institute for Plasma Physics, Wendelsteinstr. 1, D-17491 Greifswald; Thakur, S. C.
2016-04-15
Complexities of flow patterns in the azimuthal cross-section of a cylindrical magnetized helicon plasma and the corresponding plasma dynamics are investigated by means of a novel scheme for time delay estimation velocimetry. The advantage of this introduced method is the capability of calculating the time-averaged 2D velocity fields of propagating wave-like structures and patterns in complex spatiotemporal data. It is able to distinguish and visualize the details of simultaneously present superimposed entangled dynamics and it can be applied to fluid-like systems exhibiting frequently repeating patterns (e.g., waves in plasmas, waves in fluids, dynamics in planetary atmospheres, etc.). The velocity calculationsmore » are based on time delay estimation obtained from cross-phase analysis of time series. Each velocity vector is unambiguously calculated from three time series measured at three different non-collinear spatial points. This method, when applied to fast imaging, has been crucial to understand the rich plasma dynamics in the azimuthal cross-section of a cylindrical linear magnetized helicon plasma. The capabilities and the limitations of this velocimetry method are discussed and demonstrated for two completely different plasma regimes, i.e., for quasi-coherent wave dynamics and for complex broadband wave dynamics involving simultaneously present multiple instabilities.« less
O'Neill, Andrea; Erikson, Li; Barnard, Patrick
2017-01-01
While global climate models (GCMs) provide useful projections of near-surface wind vectors into the 21st century, resolution is not sufficient enough for use in regional wave modeling. Statistically downscaled GCM projections from Multivariate Adaptive Constructed Analogues provide daily averaged near-surface winds at an appropriate spatial resolution for wave modeling within the orographically complex region of San Francisco Bay, but greater resolution in time is needed to capture the peak of storm events. Short-duration high wind speeds, on the order of hours, are usually excluded in statistically downscaled climate models and are of key importance in wave and subsequent coastal flood modeling. Here we present a temporal downscaling approach, similar to constructed analogues, for near-surface winds suitable for use in local wave models and evaluate changes in wind and wave conditions for the 21st century. Reconstructed hindcast winds (1975–2004) recreate important extreme wind values within San Francisco Bay. A computationally efficient method for simulating wave heights over long time periods was used to screen for extreme events. Wave hindcasts show resultant maximum wave heights of 2.2 m possible within the Bay. Changes in extreme over-water wind speeds suggest contrasting trends within the different regions of San Francisco Bay, but 21th century projections show little change in the overall magnitude of extreme winds and locally generated waves.
Renn, Jürgen
2015-01-01
ABSTRACT This paper introduces a conceptual framework for the evolution of complex systems based on the integration of regulatory network and niche construction theories. It is designed to apply equally to cases of biological, social and cultural evolution. Within the conceptual framework we focus especially on the transformation of complex networks through the linked processes of externalization and internalization of causal factors between regulatory networks and their corresponding niches and argue that these are an important part of evolutionary explanations. This conceptual framework extends previous evolutionary models and focuses on several challenges, such as the path‐dependent nature of evolutionary change, the dynamics of evolutionary innovation and the expansion of inheritance systems. J. Exp. Zool. (Mol. Dev. Evol.) 324B: 565–577, 2015. © 2015 The Authors. Journal of Experimental Zoology Part B: Molecular and Developmental Evolution published by Wiley Periodicals, Inc. PMID:26097188
A regulatory network to segregate the identity of neuronal subtypes.
Lee, Seunghee; Lee, Bora; Joshi, Kaumudi; Pfaff, Samuel L; Lee, Jae W; Lee, Soo-Kyung
2008-06-01
Spinal motor neurons (MNs) and V2 interneurons (V2-INs) are specified by two related LIM-complexes, MN-hexamer and V2-tetramer, respectively. Here we show how multiple parallel and complementary feedback loops are integrated to assign these two cell fates accurately. While MN-hexamer response elements (REs) are specific to MN-hexamer, V2-tetramer-REs can bind both LIM-complexes. In embryonic MNs, however, two factors cooperatively suppress the aberrant activation of V2-tetramer-REs. First, LMO4 blocks V2-tetramer assembly. Second, MN-hexamer induces a repressor, Hb9, which binds V2-tetramer-REs and suppresses their activation. V2-INs use a similar approach; V2-tetramer induces a repressor, Chx10, which binds MN-hexamer-REs and blocks their activation. Thus, our study uncovers a regulatory network to segregate related cell fates, which involves reciprocal feedforward gene regulatory loops.
Zylberberg, Claudia; Matosevic, Sandro
2016-11-01
Liposomes were the first nanoscale drug to be approved for clinical use in 1995. Since then, the technology has grown considerably, and pioneering recent work in liposome-based delivery systems has brought about remarkable developments with significant clinical implications. This includes long-circulating liposomes, stimuli-responsive liposomes, nebulized liposomes, elastic liposomes for topical, oral and transdermal delivery and covalent lipid-drug complexes for improved drug plasma membrane crossing and targeting to specific organelles. While the regulatory bodies' opinion on liposomes is well-documented, current guidance that address new delivery systems are not. This review describes, in depth, the current state-of-the-art of these new liposomal delivery systems and provides a critical overview of the current regulatory landscape surrounding commercialization efforts of higher-level complexity systems, the expected requirements and the hurdles faced by companies seeking to bring novel liposome-based systems for clinical use to market.
Deák, Zsuzsanna; Sass, László; Kiss, Eva; Vass, Imre
2014-09-01
Fluorescence yield relaxation following a light pulse was studied in various cyanobacteria under aerobic and microaerobic conditions. In Synechocystis PCC 6803 fluorescence yield decays in a monotonous fashion under aerobic conditions. However, under microaerobic conditions the decay exhibits a wave feature showing a dip at 30-50 ms after the flash followed by a transient rise, reaching maximum at ~1s, before decaying back to the initial level. The wave phenomenon can also be observed under aerobic conditions in cells preilluminated with continuous light. Illumination preconditions cells for the wave phenomenon transiently: for few seconds in Synechocystis PCC 6803, but up to one hour in Thermosynechocystis elongatus BP-1. The wave is eliminated by inhibition of plastoquinone binding either to the QB site of Photosystem-II or the Qo site of cytochrome b6f complex by 3-(3',4'-dichlorophenyl)-1,1-dimethylurea or 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone, respectively. The wave is also absent in mutants, which lack either Photosystem-I or the NAD(P)H-quinone oxidoreductase (NDH-1) complex. Monitoring the redox state of the plastoquinone pool revealed that the dip of the fluorescence wave corresponds to transient oxidation, whereas the following rise to re-reduction of the plastoquinone pool. It is concluded that the unusual wave feature of fluorescence yield relaxation reflects transient oxidation of highly reduced plastoquinone pool by Photosystem-I followed by its re-reduction from stromal components via the NDH-1 complex, which is transmitted back to the fluorescence yield modulator primary quinone electron acceptor via charge equilibria. Potential applications of the wave phenomenon in studying photosynthetic and respiratory electron transport are discussed. This article is part of a special issue entitled: photosynthesis research for sustainability: keys to produce clean energy. Copyright © 2014 Elsevier B.V. All rights reserved.
Rostami, Javad; Chen, Jingming; Tse, Peter W.
2017-01-01
Ultrasonic guided waves have been extensively applied for non-destructive testing of plate-like structures particularly pipes in past two decades. In this regard, if a structure has a simple geometry, obtained guided waves’ signals are easy to explain. However, any small degree of complexity in the geometry such as contacting with other materials may cause an extra amount of complication in the interpretation of guided wave signals. The problem deepens if defects have irregular shapes such as natural corrosion. Signal processing techniques that have been proposed for guided wave signals’ analysis are generally good for simple signals obtained in a highly controlled experimental environment. In fact, guided wave signals in a real situation such as the existence of natural corrosion in wall-covered pipes are much more complicated. Considering pipes in residential buildings that pass through concrete walls, in this paper we introduced Smooth Empirical Mode Decomposition (SEMD) to efficiently separate overlapped guided waves. As empirical mode decomposition (EMD) which is a good candidate for analyzing non-stationary signals, suffers from some shortcomings, wavelet transform was adopted in the sifting stage of EMD to improve its outcome in SEMD. However, selection of mother wavelet that suits best for our purpose plays an important role. Since in guided wave inspection, the incident waves are well known and are usually tone-burst signals, we tailored a complex tone-burst signal to be used as our mother wavelet. In the sifting stage of EMD, wavelet de-noising was applied to eliminate unwanted frequency components from each IMF. SEMD greatly enhances the performance of EMD in guided wave analysis for highly contaminated signals. In our experiment on concrete covered pipes with natural corrosion, this method not only separates the concrete wall indication clearly in time domain signal, a natural corrosion with complex geometry that was hidden and located inside the concrete section was successfully exposed. PMID:28178220
Joint body and surface wave tomography applied to the Toba caldera complex (Indonesia)
NASA Astrophysics Data System (ADS)
Jaxybulatov, Kairly; Koulakov, Ivan; Shapiro, Nikolai
2016-04-01
We developed a new algorithm for a joint body and surface wave tomography. The algorithm is a modification of the existing LOTOS code (Koulakov, 2009) developed for local earthquake tomography. The input data for the new method are travel times of P and S waves and dispersion curves of Rayleigh and Love waves. The main idea is that the two data types have complementary sensitivities. The body-wave data have good resolution at depth, where we have enough crossing rays between sources and receivers, whereas the surface waves have very good near-surface resolution. The surface wave dispersion curves can be retrieved from the correlations of the ambient seismic noise and in this case the sampled path distribution does not depend on the earthquake sources. The contributions of the two data types to the inversion are controlled by the weighting of the respective equations. One of the clearest cases where such approach may be useful are volcanic systems in subduction zones with their complex magmatic feeding systems that have deep roots in the mantle and intermediate magma chambers in the crust. In these areas, the joint inversion of different types of data helps us to build a comprehensive understanding of the entire system. We apply our algorithm to data collected in the region surrounding the Toba caldera complex (north Sumatra, Indonesia) during two temporary seismic experiments (IRIS, PASSCAL, 1995, GFZ, LAKE TOBA, 2008). We invert 6644 P and 5240 S wave arrivals and ~500 group velocity dispersion curves of Rayleigh and Love waves. We present a series of synthetic tests and real data inversions which show that joint inversion approach gives more reliable results than the separate inversion of two data types. Koulakov, I., LOTOS code for local earthquake tomographic inversion. Benchmarks for testing tomographic algorithms, Bull. seism. Soc. Am., 99(1), 194-214, 2009, doi:10.1785/0120080013
NASA Astrophysics Data System (ADS)
Marjani, A.; Allahdadi, M.
2016-02-01
Sitka, AK is included in Region X of FEMA Flood Hazard Mapping. The scoped shoreline is located east of the Sitka Sound connecting Sitka to the Pacific waters through a semi-narrow continental shelf. Wave hindcast is a fundamental component of Coastal Flood Risk Study Process. SWAN model on an unstructured mesh was used to determine the characteristics of waves along the Sitka shoreline. This area is substantially affected by a combination of both offshore waves (swells) and waves generated by severe local winds. The bathymetry inside the Sitka Sound and the nearshore areas along the Sitka coastline is very complex and includes many abrupt deepening as a result of geological characteristics or large tidal currents. The present study provides a brief review of the steps and challenges for a reliable wave modeling over this area. The requirement for running the model in non-stationary mode in combination with the mentioned complexities initiated instabilities regarding intense refractions that cause unrealistic large values for the peak period and the wave height. Refining the computational mesh over the areas with great depth gradients as well as increasing the spectral grid resolution and decreasing time steps did not satisfactorily resolve the above issue. Choosing an appropriate CFL Limiters on Spectral Propagation Velocities in SWAN setup (which is not considered in the default settings) could properly treat this instability (See attached Figure). The model offshore boundary was prescribed using wave data obtained from the WIS buoys, while wind forcing was resulted as a combination of Sitka airport and offshore Buoy wind data. Model performance in transformation of swells from the open boundary was evaluated using two more offshore WIS buoy data. A 1D model transferred the extracted wave data from SWAN to the surfzone along each selected transect for each storm event. The the final production was runup with different recurrence periods along the shoreline.
USDA-ARS?s Scientific Manuscript database
During development, trithorax group (trxG) chromatin remodeling complexes counteract repression by Polycomb group (PcG) complexes to sustain active expression of key regulatory genes. Although PcG complexes are well characterized in plants, little is known about trxG activities. Here we demonstrate ...
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... Change Relating to Complex Order Auctions September 11, 2012. Pursuant to Section 19(b)(1) of the... of the Proposed Rule Change The Exchange proposed to amend its Rules regarding complex order auctions... Exchange may activate the electronic complex order request for responses (``RFR'') auction (``COA''), which...
Rogue-wave pattern transition induced by relative frequency.
Zhao, Li-Chen; Xin, Guo-Guo; Yang, Zhan-Ying
2014-08-01
We revisit a rogue wave in a two-mode nonlinear fiber whose dynamics is described by two-component coupled nonlinear Schrödinger equations. The relative frequency between two modes can induce different rogue wave patterns transition. In particular, we find a four-petaled flower structure rogue wave can exist in the two-mode coupled system, which possesses an asymmetric spectrum distribution. Furthermore, spectrum analysis is performed on these different type rogue waves, and the spectrum relations between them are discussed. We demonstrate qualitatively that different modulation instability gain distribution can induce different rogue wave excitation patterns. These results would deepen our understanding of rogue wave dynamics in complex systems.
Brinkmann, Christian; Przyklenk, Axel; Metten, Alexander; Schiffer, Thorsten; Bloch, Wilhelm; Brixius, Klara; Gehlert, Sebastian
2017-11-01
Mitophagy is a form of autophagy for the elimination of mitochondria. Mitochondrial content and function are reduced in the skeletal muscle of patients with type 2 diabetes mellitus (T2DM). Physical training has been shown to restore mitochondrial capacity in T2DM patients, but the role of mitophagy has not been examined in this context. This study analyzes the impact of a 3-month endurance training on important skeletal muscle mitophagy regulatory proteins and oxidative phosphorylation (OXPHOS) complexes in T2DM patients. Muscle biopsies were obtained from eight overweight/obese T2DM men (61±10 years) at T1 (6 weeks pre-training), T2 (1 week pre-training), and T3 (3 to 4 days post-training). Protein contents were determined by Western blotting. The training increased mitochondrial complex II significantly (T2-T3: +29%, p = 0.037). The protein contents of mitophagy regulatory proteins (phosphorylated form of forkhead box O3A (pFOXO3A), mitochondrial E3 ubiquitin protein ligase-1 (MUL1), Bcl-2/adenovirus E1B 19-kD interacting protein-3 (BNIP3), microtubule-associated protein 1 light chain-3B (the ratio LC3B-II/LC3B-I was determined)) did not differ significantly between T1, T2, and T3. The results imply that training-induced changes in OXPHOS subunits (significant increase in complex II) are not accompanied by changes in mitophagy regulatory proteins in T2DM men. Future studies should elucidate whether acute exercise might affect mitophagic processes in T2DM patients (and whether a transient regulation of mitophagy regulatory proteins is evident) to fully clarify the role of physical activity and mitophagy for mitochondrial health in this particular patient group.
On the rogue waves propagation in non-Maxwellian complex space plasmas
DOE Office of Scientific and Technical Information (OSTI.GOV)
El-Tantawy, S. A., E-mail: samireltantawy@yahoo.com; El-Awady, E. I., E-mail: eielawady@hotmail.com; Tribeche, M., E-mail: mouloudtribeche@yahoo.fr, E-mail: mtribeche@usthb.dz
2015-11-15
The implications of the non-Maxwellian electron distributions (nonthermal/or suprathermal/or nonextensive distributions) are examined on the dust-ion acoustic (DIA) rogue/freak waves in a dusty warm plasma. Using a reductive perturbation technique, the basic set of fluid equations is reduced to a nonlinear Schrödinger equation. The latter is used to study the nonlinear evolution of modulationally unstable DIA wavepackets and to describe the rogue waves (RWs) propagation. Rogue waves are large-amplitude short-lived wave groups, routinely observed in space plasmas. The possible region for the rogue waves to exist is defined precisely for typical parameters of space plasmas. It is shown that themore » RWs strengthen for decreasing plasma nonthermality and increasing superthermality. For nonextensive electrons, the RWs amplitude exhibits a bit more complex behavior, depending on the entropic index q. Moreover, our numerical results reveal that the RWs exist with all values of the ion-to-electron temperature ratio σ for nonthermal and superthermal distributions and there is no limitation for the freak waves to propagate in both two distributions in the present plasma system. But, for nonextensive electron distribution, the bright- and dark-type waves can propagate in this case, which means that there is a limitation for the existence of freak waves. Our systematic investigation should be useful in understanding the properties of DIA solitary waves that may occur in non-Maxwellian space plasmas.« less
Like cures like: a neuroimmunological model based on electromagnetic resonance.
Shahabi, Shahram; Kasariyans, Aditya; Noorbakhsh, Farshid
2013-12-01
Recent investigations have pointed to the production of characteristic electromagnetic (EM) waves in highly diluted sterile filtrates of different microorganisms and their associated DNA molecules. Analysis of these diluted solutions that are prepared using methods almost identical to the way that homeopathic medicines are prepared has pointed to the existence of nanostructures capable of emitting EM waves. Combining these results with findings that point to the interaction of EM waves with sensory nerves with subsequent activation of homeostatic efferent pathways, we propose a model to describe mechanisms underlying the effects of homeopathic remedies. THE MODEL: Living cells and tissues are capable of generating EM waves in their physiological conditions. When a cell deviates from its physiological state, in addition to normal EM emissions, it starts to produce EM waves with altered characteristics. According to our model, the main cause of the therapeutic effects of homeopathic remedies is the occurrence of resonance between the non-physiological EM waves of the patient and extremely low-frequency EM waves produced by nanostructures present in the homeopathic remedy. Resonance occurs if the frequency and amplitude characteristics of the patient's non-physiological EM waves and those produced by nanostructures of the applied homeopathic remedy are similar. Once resonance occurs, stimulation of the patient's sensory neurons, which are sensitized due to inflammation of any origin, leads to triggering of different regulatory mechanisms, including the activation of descending antinociceptive and/or cholinergic anti-inflammatory pathways, which leads to the restoration of homeostasis.
A shallow water model for the propagation of tsunami via Lattice Boltzmann method
NASA Astrophysics Data System (ADS)
Zergani, Sara; Aziz, Z. A.; Viswanathan, K. K.
2015-01-01
An efficient implementation of the lattice Boltzmann method (LBM) for the numerical simulation of the propagation of long ocean waves (e.g. tsunami), based on the nonlinear shallow water (NSW) wave equation is presented. The LBM is an alternative numerical procedure for the description of incompressible hydrodynamics and has the potential to serve as an efficient solver for incompressible flows in complex geometries. This work proposes the NSW equations for the irrotational surface waves in the case of complex bottom elevation. In recent time, equation involving shallow water is the current norm in modelling tsunami operations which include the propagation zone estimation. Several test-cases are presented to verify our model. Some implications to tsunami wave modelling are also discussed. Numerical results are found to be in excellent agreement with theory.
Dust acoustic cnoidal waves in a polytropic complex plasma
NASA Astrophysics Data System (ADS)
El-Labany, S. K.; El-Taibany, W. F.; Abdelghany, A. M.
2018-01-01
The nonlinear characteristics of dust acoustic (DA) waves in an unmagnetized collisionless complex plasma containing adiabatic electrons and ions and negatively charged dust grains (including the effects of modified polarization force) are investigated. Employing the reductive perturbation technique, a Korteweg-de Vries-Burgers (KdVB) equation is derived. The analytical solution for the KdVB equation is discussed. Also, the bifurcation and phase portrait analyses are presented to recognize different types of possible solutions. The dependence of the properties of nonlinear DA waves on the system parameters is investigated. It has been shown that an increase in the value of the modified polarization parameter leads to a fast decay and diminishes the oscillation amplitude of the DA damped cnoidal wave. The relevance of our findings and their possible applications to laboratory and space plasma situations is discussed.
Ablation of multi-wavelet re-entry: general principles and in silico analyses.
Spector, Peter S; Correa de Sa, Daniel D; Tischler, Ethan S; Thompson, Nathaniel C; Habel, Nicole; Stinnett-Donnelly, Justin; Benson, Bryce E; Bielau, Philipp; Bates, Jason H T
2012-11-01
Catheter ablation strategies for treatment of cardiac arrhythmias are quite successful when targeting spatially constrained substrates. Complex, dynamic, and spatially varying substrates, however, pose a significant challenge for ablation, which delivers spatially fixed lesions. We describe tissue excitation using concepts of surface topology which provides a framework for addressing this challenge. The aim of this study was to test the efficacy of mechanism-based ablation strategies in the setting of complex dynamic substrates. We used a computational model of propagation through electrically excitable tissue to test the effects of ablation on excitation patterns of progressively greater complexity, from fixed rotors to multi-wavelet re-entry. Our results indicate that (i) focal ablation at a spiral-wave core does not result in termination; (ii) termination requires linear lesions from the tissue edge to the spiral-wave core; (iii) meandering spiral-waves terminate upon collision with a boundary (linear lesion or tissue edge); (iv) the probability of terminating multi-wavelet re-entry is proportional to the ratio of total boundary length to tissue area; (v) the efficacy of linear lesions varies directly with the regional density of spiral-waves. We establish a theoretical framework for re-entrant arrhythmias that explains the requirements for their successful treatment. We demonstrate the inadequacy of focal ablation for spatially fixed spiral-waves. Mechanistically guided principles for ablating multi-wavelet re-entry are provided. The potential to capitalize upon regional heterogeneity of spiral-wave density for improved ablation efficacy is described.
Slow Feature Analysis on Retinal Waves Leads to V1 Complex Cells
Dähne, Sven; Wilbert, Niko; Wiskott, Laurenz
2014-01-01
The developing visual system of many mammalian species is partially structured and organized even before the onset of vision. Spontaneous neural activity, which spreads in waves across the retina, has been suggested to play a major role in these prenatal structuring processes. Recently, it has been shown that when employing an efficient coding strategy, such as sparse coding, these retinal activity patterns lead to basis functions that resemble optimal stimuli of simple cells in primary visual cortex (V1). Here we present the results of applying a coding strategy that optimizes for temporal slowness, namely Slow Feature Analysis (SFA), to a biologically plausible model of retinal waves. Previously, SFA has been successfully applied to model parts of the visual system, most notably in reproducing a rich set of complex-cell features by training SFA with quasi-natural image sequences. In the present work, we obtain SFA units that share a number of properties with cortical complex-cells by training on simulated retinal waves. The emergence of two distinct properties of the SFA units (phase invariance and orientation tuning) is thoroughly investigated via control experiments and mathematical analysis of the input-output functions found by SFA. The results support the idea that retinal waves share relevant temporal and spatial properties with natural visual input. Hence, retinal waves seem suitable training stimuli to learn invariances and thereby shape the developing early visual system such that it is best prepared for coding input from the natural world. PMID:24810948
Alternative descriptions of wave and particle aspects of the harmonic oscillator
NASA Technical Reports Server (NTRS)
Schuch, Dieter
1993-01-01
The dynamical properties of the wave and particle aspects of the harmonic oscillator can be studied with the help of the time-dependent Schroedinger equation (SE). Especially the time-dependence of maximum and width of Gaussian wave packet solutions allow to show the evolution and connections of those two complementary aspects. The investigation of the relations between the equations describing wave and particle aspects leads to an alternative description of the considered systems. This can be achieved by means of a Newtonian equation for a complex variable in connection with a conservation law for a nonclassical angular momentum-type quantity. With the help of this complex variable, it is also possible to develop a Hamiltonian formalism for the wave aspect contained in the SE, which allows to describe the dynamics of the position and momentum uncertainties. In this case the Hamiltonian function is equivalent to the difference between the mean value of the Hamiltonian operator and the classical Hamiltonian function.
NASA Astrophysics Data System (ADS)
Raad Hussein, Alaa; Badri Albarody, Thar M.; Megat Yusoff, Puteri Sri Melor Bt
2018-05-01
Nowadays there is no viable non-destructive method that could detect flaws in complex composite products. Such a method could provide unique tools to allow engineers to minimize time consumption and cost during the evaluation of various product parameters without disturbing production. The latest research and development on propagation waves introduce micro, radio and millimetre waves as new potential non-destructive test methods for evaluation of mechanical flaws and prediction of failure in a product during production. This paper focuses on recent developments, usage, classification of electromagnetic waves under the range of radio frequency, millimetre and micro-waves. In addition, this paper reviews the application of propagation wave and proposed a new health monitoring technique based on Doppler Effect for vibration measurement in complex composite structures. Doppler Effect is influenced by dynamic behaviour of the composite structures and both are effect by flaws occurred inside the structure. Composite manufacturers, especially Aerospace industry are demanding these methods comprehensively inspect and evaluate the damages and defects in their products.
Wave Geometry: a Plurality of Singularities
NASA Astrophysics Data System (ADS)
Berry, M. V.
Five interconnected wave singularities are discussed: phase monopoles, at eigenvalue degeneracies in parameter space, where the 2-form generating the geomeeic phase is singular, phase dislocations, at zeros of complex wavefunctions in position space, where different wavefronts (surfaces of constant phase) meet; caustics, that is envelopes (foci) of families of classical paths or geometrical rays, where real rays are born violently and which are complementary to dislocations; Stokes sets, at which a complex ray is born gently where it is maximally dominated by another ray; and complex degeneracies, which are the sources of adiabatic quantum transtions in analytic Hamiltonians.
Controllable optical rogue waves via nonlinearity management.
Yang, Zhengping; Zhong, Wei-Ping; Belić, Milivoj; Zhang, Yiqi
2018-03-19
Using a similarity transformation, we obtain analytical solutions to a class of nonlinear Schrödinger (NLS) equations with variable coefficients in inhomogeneous Kerr media, which are related to the optical rogue waves of the standard NLS equation. We discuss the dynamics of such optical rogue waves via nonlinearity management, i.e., by selecting the appropriate nonlinearity coefficients and integration constants, and presenting the solutions. In addition, we investigate higher-order rogue waves by suitably adjusting the nonlinearity coefficient and the rogue wave parameters, which could help in realizing complex but controllable optical rogue waves in properly engineered fibers and other photonic materials.
The Dynamics and Evolution of Poles and Rogue Waves for Nonlinear Schrödinger Equations*
NASA Astrophysics Data System (ADS)
Chiu, Tin Lok; Liu, Tian Yang; Chan, Hiu Ning; Wing Chow, Kwok
2017-09-01
Rogue waves are unexpectedly large deviations from equilibrium or otherwise calm positions in physical systems, e.g. hydrodynamic waves and optical beam intensities. The profiles and points of maximum displacements of these rogue waves are correlated with the movement of poles of the exact solutions extended to the complex plane through analytic continuation. Such links are shown to be surprisingly precise for the first order rogue wave of the nonlinear Schrödinger (NLS) and the derivative NLS equations. A computational study on the second order rogue waves of the NLS equation also displays remarkable agreements.
How Soluble GARP Enhances TGFβ Activation.
Fridrich, Sven; Hahn, Susanne A; Linzmaier, Marion; Felten, Matthias; Zwarg, Jenny; Lennerz, Volker; Tuettenberg, Andrea; Stöcker, Walter
2016-01-01
GARP (glycoprotein A repetitions predominant) is a cell surface receptor on regulatory T-lymphocytes, platelets, hepatic stellate cells and certain cancer cells. Its described function is the binding and accommodation of latent TGFβ (transforming growth factor), before the activation and release of the mature cytokine. For regulatory T cells it was shown that a knockdown of GARP or a treatment with blocking antibodies dramatically decreases their immune suppressive capacity. This confirms a fundamental role of GARP in the basic function of regulatory T cells. Prerequisites postulated for physiological GARP function include membrane anchorage of GARP, disulfide bridges between the propeptide of TGFβ and GARP and connection of this propeptide to αvβ6 or αvβ8 integrins of target cells during mechanical TGFβ release. Other studies indicate the existence of soluble GARP complexes and a functionality of soluble GARP alone. In order to clarify the underlying molecular mechanism, we expressed and purified recombinant TGFβ and a soluble variant of GARP. Surprisingly, soluble GARP and TGFβ formed stable non-covalent complexes in addition to disulfide-coupled complexes, depending on the redox conditions of the microenvironment. We also show that soluble GARP alone and the two variants of complexes mediate different levels of TGFβ activity. TGFβ activation is enhanced by the non-covalent GARP-TGFβ complex already at low (nanomolar) concentrations, at which GARP alone does not show any effect. This supports the idea of soluble GARP acting as immune modulator in vivo.
1985-03-01
interferometry and computer- R - spanwise coordinate, ft assisted tomography ( CAT ) are used to determine the transonic velocity field of a model rotor...and extracting fringe-order functions, the c data are transferred to a CAT code.- The CAT code Ui transmitted wave complex amplitude then calculates...the perturbation velocity in sev- eral planes above the blade surface. The values Ur reference wave complex amplitude from the holography- CAT method
Oscillatory erosion and transport flume with superimposed unidirectional flow
Jepsen, Richard A.; Roberts, Jesse D.
2004-01-20
A method and apparatus for measuring erosion rates of sediments and at high shear stresses due to complex wave action with, or without, a superimposed unidirectional current. Water is forced in a channel past an exposed sediment core sample, which erodes sediments when a critical shear stress has been exceeded. The height of the core sample is adjusted during testing so that the sediment surface remains level with the bottom of the channel as the sediments erode. Complex wave action is simulated by driving tandom piston/cylinder mechanisms with computer-controlled stepper motors. Unidirectional flow, forced by a head difference between two open tanks attached to each end of the channel, may be superimposed on to the complex wave action. Sediment traps may be used to collect bedload sediments. The total erosion rate equals the change in height of the sediment core sample divided by a fixed period of time.
Calabrese, Camilla; Vigorito, Annalisa; Maris, Assimo; Mariotti, Sergio; Fathi, Pantea; Geppert, Wolf D; Melandri, Sonia
2015-12-03
The weakly bound 1:1 complex between acrylonitrile (CH2═CHCN) and water has been characterized spectroscopically in the millimeter wave range (59.6-74.4 GHz) using a Free Jet Absorption Millimeter Wave spectrometer. Precise values of the rotational and quartic centrifugal distortion constants have been obtained from the measured frequencies of the normal and isotopically substituted water moiety (DOH, DOD, H(18)OH). Structural parameters have been estimated from the rotational constants and their differences among isotopologues: the complex has a planar structure with the two subunits held together by a O-H···N (2.331(3) Å) and a C-H···O (2.508(4) Å) interaction. The ab initio intermolecular binding energy, obtained at the counterpoise corrected MP2/aug-cc-pVTZ level of calculation, is De = 24.4 kJ mol(-1).
Jeanne C. Chambers; Jeremy D. Maestas; David A. Pyke; Chad S. Boyd; Mike Pellant; Amarina Wuenschel
2017-01-01
Conservation of imperiled species often demands addressing a complex suite of threats that undermine species viability. Regulatory approaches, such as the US Endangered Species Act (1973), tend to focus on anthropogenic threats through adoption of policies and regulatory mechanisms. However, persistent ecosystem-based threats, such as invasive species and altered...
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2012-01-31
... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66235; File No. SR-CBOE-2011-114] Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Approving a Proposed Rule Change Relating to Complex Order Processing in Hybrid 3.0 Classes January 25, 2012. I. Introduction On November 29, 2011, the Chicago Board Options...
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2012-01-26
... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66207; File No. SR-CBOE-2012-004] Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Related to Automatic Execution and Complex Order Price Check Parameter Features January 20, 2012. Pursuant to Sectio...
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Shear wave splitting and shear wave splitting tomography of the southern Puna plateau
NASA Astrophysics Data System (ADS)
Calixto, Frank J.; Robinson, Danielle; Sandvol, Eric; Kay, Suzanne; Abt, David; Fischer, Karen; Heit, Ben; Yuan, Xiaohui; Comte, Diana; Alvarado, Patricia
2014-11-01
We have investigated the seismic anisotropy beneath the Central Andean southern Puna plateau by applying shear wave splitting analysis and shear wave splitting tomography to local S waves and teleseismic SKS, SKKS and PKS phases. Overall, a very complex pattern of fast directions throughout the southern Puna plateau region and a circular pattern of fast directions around the region of the giant Cerro Galan ignimbrite complex are observed. In general, teleseismic lag times are much greater than those for local events which are interpreted to reflect a significant amount of sub and inner slab anisotropy. The complex pattern observed from shear wave splitting analysis alone is the result of a complex 3-D anisotropic structure under the southern Puna plateau. Our application of shear wave splitting tomography provides a 3-D model of anisotropy in the southern Puna plateau that shows different patterns depending on the driving mechanism of upper-mantle flow and seismic anisotropy. The trench parallel a-axes in the continental lithosphere above the slab east of 68W may be related to deformation of the overriding continental lithosphere since it is under compressive stresses which are orthogonal to the trench. The more complex pattern below the Cerro Galan ignimbrite complex and above the slab is interpreted to reflect delamination of continental lithosphere and upwelling of hot asthenosphere. The a-axes beneath the Cerro Galan, Cerro Blanco and Carachi Pampa volcanic centres at 100 km depth show some weak evidence for vertically orientated fast directions, which could be due to vertical asthenospheric flow around a delaminated block. Additionally, our splitting tomographic model shows that there is a significant amount of seismic anisotropy beneath the slab. The subslab mantle west of 68W shows roughly trench parallel horizontal a-axes that are probably driven by slab roll back and the relatively small coupling between the Nazca slab and the underlying mantle. In contrast, the subslab region (i.e. depths greater than 200 km) east of 68W shows a circular pattern of a-axes centred on a region with small strength of anisotropy (Cerro Galan and its eastern edge) which suggest the dominant mechanism is a combination of slab roll back and flow driven by an overlying abnormally heated slab or possibly a slab gap. There seems to be some evidence for vertical flow below the slab at depths of 200-400 km driven by the abnormally heated slab or slab gap. This cannot be resolved by the tomographic inversion due to the lack of ray crossings in the subslab mantle.
Hydrodynamic analysis and shape optimization for vertical axisymmetric wave energy converters
NASA Astrophysics Data System (ADS)
Zhang, Wan-chao; Liu, Heng-xu; Zhang, Liang; Zhang, Xue-wei
2016-12-01
The absorber is known to be vertical axisymmetric for a single-point wave energy converter (WEC). The shape of the wetted surface usually has a great influence on the absorber's hydrodynamic characteristics which are closely linked with the wave power conversion ability. For complex wetted surface, the hydrodynamic coefficients have been predicted traditionally by hydrodynamic software based on the BEM. However, for a systematic study of various parameters and geometries, they are too multifarious to generate so many models and data grids. This paper examines a semi-analytical method of decomposing the complex axisymmetric boundary into several ring-shaped and stepped surfaces based on the boundary discretization method (BDM) which overcomes the previous difficulties. In such case, by using the linear wave theory based on eigenfunction expansion matching method, the expressions of velocity potential in each domain, the added mass, radiation damping and wave excitation forces of the oscillating absorbers are obtained. The good astringency of the hydrodynamic coefficients and wave forces are obtained for various geometries when the discrete number reaches a certain value. The captured wave power for a same given draught and displacement for various geometries are calculated and compared. Numerical results show that the geometrical shape has great effect on the wave conversion performance of the absorber. For absorbers with the same outer radius and draught or displacement, the cylindrical type shows fantastic wave energy conversion ability at some given frequencies, while in the random sea wave, the parabolic and conical ones have better stabilization and applicability in wave power conversion.
Jia, Da; Gomez, Timothy S; Metlagel, Zoltan; Umetani, Junko; Otwinowski, Zbyszek; Rosen, Michael K; Billadeau, Daniel D
2010-06-08
We recently showed that the Wiskott-Aldrich syndrome protein (WASP) family member, WASH, localizes to endosomal subdomains and regulates endocytic vesicle scission in an Arp2/3-dependent manner. Mechanisms regulating WASH activity are unknown. Here we show that WASH functions in cells within a 500 kDa core complex containing Strumpellin, FAM21, KIAA1033 (SWIP), and CCDC53. Although recombinant WASH is constitutively active toward the Arp2/3 complex, the reconstituted core assembly is inhibited, suggesting that it functions in cells to regulate actin dynamics through WASH. FAM21 interacts directly with CAPZ and inhibits its actin-capping activity. Four of the five core components show distant (approximately 15% amino acid sequence identify) but significant structural homology to components of a complex that negatively regulates the WASP family member, WAVE. Moreover, biochemical and electron microscopic analyses show that the WASH and WAVE complexes are structurally similar. Thus, these two distantly related WASP family members are controlled by analogous structurally related mechanisms. Strumpellin is mutated in the human disease hereditary spastic paraplegia, and its link to WASH suggests that misregulation of actin dynamics on endosomes may play a role in this disorder.
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2010-09-17
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Chaotic Bohmian trajectories for stationary states
NASA Astrophysics Data System (ADS)
Cesa, Alexandre; Martin, John; Struyve, Ward
2016-09-01
In Bohmian mechanics, the nodes of the wave function play an important role in the generation of chaos. However, so far, most of the attention has been on moving nodes; little is known about the possibility of chaos in the case of stationary nodes. We address this question by considering stationary states, which provide the simplest examples of wave functions with stationary nodes. We provide examples of stationary wave functions for which there is chaos, as demonstrated by numerical computations, for one particle moving in three spatial dimensions and for two and three entangled particles in two dimensions. Our conclusion is that the motion of the nodes is not necessary for the generation of chaos. What is important is the overall complexity of the wave function. That is, if the wave function, or rather its phase, has a complex spatial variation, it will lead to complex Bohmian trajectories and hence to chaos. Another aspect of our work concerns the average Lyapunov exponent, which quantifies the overall amount of chaos. Since it is very hard to evaluate the average Lyapunov exponent analytically, which is often computed numerically, it is useful to have simple quantities that agree well with the average Lyapunov exponent. We investigate possible correlations with quantities such as the participation ratio and different measures of entanglement, for different systems and different families of stationary wave functions. We find that these quantities often tend to correlate to the amount of chaos. However, the correlation is not perfect, because, in particular, these measures do not depend on the form of the basis states used to expand the wave function, while the amount of chaos does.
Dynamic integration of splicing within gene regulatory pathways
Braunschweig, Ulrich; Gueroussov, Serge; Plocik, Alex; Graveley, Brenton R.; Blencowe, Benjamin J.
2013-01-01
Precursor mRNA splicing is one of the most highly regulated processes in metazoan species. In addition to generating vast repertoires of RNAs and proteins, splicing has a profound impact on other gene regulatory layers, including mRNA transcription, turnover, transport and translation. Conversely, factors regulating chromatin and transcription complexes impact the splicing process. This extensive cross-talk between gene regulatory layers takes advantage of dynamic spatial, physical and temporal organizational properties of the cell nucleus, and further emphasizes the importance of developing a multidimensional understanding of splicing control. PMID:23498935
Portrait of Candida Species Biofilm Regulatory Network Genes.
Araújo, Daniela; Henriques, Mariana; Silva, Sónia
2017-01-01
Most cases of candidiasis have been attributed to Candida albicans, but Candida glabrata, Candida parapsilosis and Candida tropicalis, designated as non-C. albicans Candida (NCAC), have been identified as frequent human pathogens. Moreover, Candida biofilms are an escalating clinical problem associated with significant rates of mortality. Biofilms have distinct developmental phases, including adhesion/colonisation, maturation and dispersal, controlled by complex regulatory networks. This review discusses recent advances regarding Candida species biofilm regulatory network genes, which are key components for candidiasis. Copyright © 2016 Elsevier Ltd. All rights reserved.
Extracorporeal shock wave therapy in treatment of delayed bone-tendon healing.
Wang, Lin; Qin, Ling; Lu, Hong-bin; Cheung, Wing-hoi; Yang, Hu; Wong, Wan-nar; Chan, Kai-ming; Leung, Kwok-sui
2008-02-01
Extracorporeal shock wave therapy is indicated for treatment of chronic injuries of soft tissues and delayed fracture healing and nonunion. No investigation has been conducted to study the effect of shock wave on delayed healing at the bone-tendon junction. Shock wave promotes osteogenesis, regeneration of fibrocartilage zone, and remodeling of healing tissue in delayed healing of bone-tendon junction surgical repair. Controlled laboratory study. Twenty-eight mature rabbits were used for establishing a delayed healing model at the patella-patellar tendon complex after partial patellectomy and then divided into control and shock wave groups. In the shock wave group, a single shock wave treatment was given at week 6 postoperatively to the patella-patellar tendon healing complex. Seven samples were harvested at week 8 and 7 samples at week 12 for radiologic, densitometric, histologic, and mechanical evaluations. Radiographic measurements showed 293.4% and 185.8% more new bone formation at the patella-patellar tendon healing junction in the shock wave group at weeks 8 and 12, respectively. Significantly better bone mineral status was found in the week 12 shock wave group. Histologically, the shock wave group showed more advanced remodeling in terms of better alignment of collagen fibers and thicker and more mature regenerated fibrocartilage zone at both weeks 8 and 12. Mechanical testing showed 167.7% and 145.1% higher tensile load and strength in the shock wave group at week 8 and week 12, respectively, compared with controls. Extracorporeal shock wave promotes osteogenesis, regeneration of fibrocartilage zone, and remodeling in the delayed bone-to-tendon healing junction in rabbits. These results provide a foundation for future clinical studies toward establishment of clinical indication for treatment of delayed bone-to-tendon junction healing.
Takahashi, Kazuhide; Suzuki, Katsuo
2010-11-01
Membrane targeting of WAVE2 along microtubules to phosphatidylinositol 3,4,5-triphosphate (PIP(3)) in response to an extracellular stimulus requires Rac1, Pak1, stathmin, and EB1. However, whether WAVE2 interacts directly with PIP(3) or not remains unclear. We demonstrate that insulin-like growth factor I (IGF-I) induces WAVE2 membrane targeting, accompanied by phosphorylation of Pak1 at serine 199/204 (Ser199/204) and stathmin at Ser38 in the inner cytoplasmic region. This is spatially independent of the membrane region where the IGF-I receptor (IGF-IR) is locally activated. WAVE2, phosphorylated Pak1, and phosphorylated stathmin located at the microtubule ends began to accumulate at the leading edge of cells in close proximity to PIP(3) that was produced in a phosphatidylinositol 3-kinase (PI 3-kinase)-dependent manner. The PIP(3)-beads binding assay revealed that insulin receptor substrate p53 (IRSp53) and actin rather than WAVE2 bound to PIP(3). IRSp53 constitutively associated with WAVE2 and these two proteins colocalized with PIP(3) at the leading edge after IGF-I stimulation. Suppression of IRSp53 expression by two independent small interfering RNAs (siRNAs) completely inhibited IGF-I-induced membrane targeting and local accumulation of WAVE2 at the leading edge of cells. We propose that IRSp53 constitutively forms a complex with WAVE2 and is crucial for membrane targeting followed by local accumulation of WAVE2 at the leading edge of cells through linking WAVE2 to PIP(3) that is produced near locally activated IGF-IR in response to IGF-I. Copyright (c) 2010 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Qian, Y.; Wei, S.; Wu, W.; Ni, S.
2017-12-01
Among various types of 3D heterogeneity in the Earth, trench might be the most complex systems, which includes rapidly varying bathymetry and usually thick sediment below water layer. These structure complexities can cause substantial waveform complexities on seismograms, but their corresponding impact on the earthquake source studies has not yet been well understood. Here we explore those effects via studies of two moderate aftershocks (one near the coast while the other close to the Peru-Chile trench axis) in the 2015 Illapel earthquake sequence. The horizontal locations and depths of these two events are poorly constrained and the reported results of various agencies display substantial variations. Thus, we first relocated the epicenters using the P-wave first arrivals and determined other parameters by waveform fitting. In a jackknifing way, we found that the trench event has large differences between regional and teleseismic solutions, in particular for depth, while the coastal event shows consistent results. The teleseismic P/Pdiff waves between these two events also display distinctly different features. More specifically, the trench event has more complex P/Pdiff waves and stronger coda waves, in terms of amplitude and duration (longer than 100s). The coda waves are coherent across stations at different distances and azimuths, indicating a more likely origin of scattering waves due to 3D heterogeneity near trench. To quantitatively model those 3D effects, we adopted a hybrid waveform simulation approach that computes the 3D wavefield in the source region by the Spectral Element Method (SEM) and then propagates the wavefield to teleseismic and shadow zone distances through the Direct Solution Method (DSM). We incorporated the GEBCO bathymetry and water layer into the SEM simulations and assumed the IASP91 1D model for DSM computation. Comparing with the poor 1D synthetics fitting to the data, we do obtain dramatic improvement in 3D waveform fittings across a series of frequency bands. With sensitivity tests of 3D waveform modeling, the centroid longitude and depth for the near trench event are refined. Our study suggests that the complex trench structure must be taken into account for a reliable analysis of shallow earthquake near trench, in particular for the shallowest tsunamigenic earthquakes.
2011-01-01
Background To make sense out of gene expression profiles, such analyses must be pushed beyond the mere listing of affected genes. For example, if a group of genes persistently display similar changes in expression levels under particular experimental conditions, and the proteins encoded by these genes interact and function in the same cellular compartments, this could be taken as very strong indicators for co-regulated protein complexes. One of the key requirements is having appropriate tools to detect such regulatory patterns. Results We have analyzed the global adaptations in gene expression patterns in the budding yeast when the Hsp90 molecular chaperone complex is perturbed either pharmacologically or genetically. We integrated these results with publicly accessible expression, protein-protein interaction and intracellular localization data. But most importantly, all experimental conditions were simultaneously and dynamically visualized with an animation. This critically facilitated the detection of patterns of gene expression changes that suggested underlying regulatory networks that a standard analysis by pairwise comparison and clustering could not have revealed. Conclusions The results of the animation-assisted detection of changes in gene regulatory patterns make predictions about the potential roles of Hsp90 and its co-chaperone p23 in regulating whole sets of genes. The simultaneous dynamic visualization of microarray experiments, represented in networks built by integrating one's own experimental with publicly accessible data, represents a powerful discovery tool that allows the generation of new interpretations and hypotheses. PMID:21672238
Dombo, Eileen A; Kays, Lisa; Weller, Katelyn
2014-10-01
The world that social work exists in is no longer defined by traditional physical settings and boundaries, such as schools, agencies, or even offices. With the advent of the Internet and digital communications, social work now exists in a far more complex reality, with clients and social workers engaging across multiple platforms, and sometimes even unintentionally and without one another's awareness. The implications of this can be ethical, practical, regulatory, and personal. This article explores these areas of concern and suggests strategies professionals can use to navigate these complex issues related to technology and clinical practice.
Intrinsic noise and deviations from criticality in Boolean gene-regulatory networks
NASA Astrophysics Data System (ADS)
Villegas, Pablo; Ruiz-Franco, José; Hidalgo, Jorge; Muñoz, Miguel A.
2016-10-01
Gene regulatory networks can be successfully modeled as Boolean networks. A much discussed hypothesis says that such model networks reproduce empirical findings the best if they are tuned to operate at criticality, i.e. at the borderline between their ordered and disordered phases. Critical networks have been argued to lead to a number of functional advantages such as maximal dynamical range, maximal sensitivity to environmental changes, as well as to an excellent tradeoff between stability and flexibility. Here, we study the effect of noise within the context of Boolean networks trained to learn complex tasks under supervision. We verify that quasi-critical networks are the ones learning in the fastest possible way -even for asynchronous updating rules- and that the larger the task complexity the smaller the distance to criticality. On the other hand, when additional sources of intrinsic noise in the network states and/or in its wiring pattern are introduced, the optimally performing networks become clearly subcritical. These results suggest that in order to compensate for inherent stochasticity, regulatory and other type of biological networks might become subcritical rather than being critical, all the most if the task to be performed has limited complexity.
Extensive cross-regulation of post-transcriptional regulatory networks in Drosophila
Stoiber, Marcus H.; Olson, Sara; May, Gemma E.; ...
2015-08-20
In eukaryotic cells, RNAs exist as ribonucleoprotein particles (RNPs). Despite the importance of these complexes in many biological processes, including splicing, polyadenylation, stability, transportation, localization, and translation, their compositions are largely unknown. We affinity-purified 20 distinct RNA-binding proteins (RBPs) from cultured Drosophila melanogaster cells under native conditions and identified both the RNA and protein compositions of these RNP complexes. We identified “high occupancy target” (HOT) RNAs that interact with the majority of the RBPs we surveyed. HOT RNAs encode components of the nonsense-mediated decay and splicing machinery, as well as RNA-binding and translation initiation proteins. The RNP complexes contain proteinsmore » and mRNAs involved in RNA binding and post-transcriptional regulation. Genes with the capacity to produce hundreds of mRNA isoforms, ultracomplex genes, interact extensively with heterogeneous nuclear ribonuclear proteins (hnRNPs). Our data are consistent with a model in which subsets of RNPs include mRNA and protein products from the same gene, indicating the widespread existence of auto-regulatory RNPs. Lastly, from the simultaneous acquisition and integrative analysis of protein and RNA constituents of RNPs, we identify extensive cross-regulatory and hierarchical interactions in post-transcriptional control.« less
Extensive cross-regulation of post-transcriptional regulatory networks in Drosophila
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stoiber, Marcus H.; Olson, Sara; May, Gemma E.
In eukaryotic cells, RNAs exist as ribonucleoprotein particles (RNPs). Despite the importance of these complexes in many biological processes, including splicing, polyadenylation, stability, transportation, localization, and translation, their compositions are largely unknown. We affinity-purified 20 distinct RNA-binding proteins (RBPs) from cultured Drosophila melanogaster cells under native conditions and identified both the RNA and protein compositions of these RNP complexes. We identified “high occupancy target” (HOT) RNAs that interact with the majority of the RBPs we surveyed. HOT RNAs encode components of the nonsense-mediated decay and splicing machinery, as well as RNA-binding and translation initiation proteins. The RNP complexes contain proteinsmore » and mRNAs involved in RNA binding and post-transcriptional regulation. Genes with the capacity to produce hundreds of mRNA isoforms, ultracomplex genes, interact extensively with heterogeneous nuclear ribonuclear proteins (hnRNPs). Our data are consistent with a model in which subsets of RNPs include mRNA and protein products from the same gene, indicating the widespread existence of auto-regulatory RNPs. Lastly, from the simultaneous acquisition and integrative analysis of protein and RNA constituents of RNPs, we identify extensive cross-regulatory and hierarchical interactions in post-transcriptional control.« less
Gillespie, Mark A; Gold, Elizabeth S; Ramsey, Stephen A; Podolsky, Irina; Aderem, Alan; Ranish, Jeffrey A
2015-01-01
LXR–cofactor complexes activate the gene expression program responsible for cholesterol efflux in macrophages. Inflammation antagonizes this program, resulting in foam cell formation and atherosclerosis; however, the molecular mechanisms underlying this antagonism remain to be fully elucidated. We use promoter enrichment-quantitative mass spectrometry (PE-QMS) to characterize the composition of gene regulatory complexes assembled at the promoter of the lipid transporter Abca1 following downregulation of its expression. We identify a subset of proteins that show LXR ligand- and binding-dependent association with the Abca1 promoter and demonstrate they differentially control Abca1 expression. We determine that NCOA5 is linked to inflammatory Toll-like receptor (TLR) signaling and establish that NCOA5 functions as an LXR corepressor to attenuate Abca1 expression. Importantly, TLR3–LXR signal crosstalk promotes recruitment of NCOA5 to the Abca1 promoter together with loss of RNA polymerase II and reduced cholesterol efflux. Together, these data significantly expand our knowledge of regulatory inputs impinging on the Abca1 promoter and indicate a central role for NCOA5 in mediating crosstalk between pro-inflammatory and anti-inflammatory pathways that results in repression of macrophage cholesterol efflux. PMID:25755249
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An analysis of the early-warning system in emerging markets for reducing the financial crisis
NASA Astrophysics Data System (ADS)
Shen, Xiangguang; Song, Xiaozhong
2009-07-01
The large number of financial crises in emerging markets over the past ten years has left many observers, both from academia and financial institutions, puzzled by an apparent lack of homogenous causal relations between endogenous economic variables and the bursting of large financial shocks. The frequency of financial crises in the last 20 years can be attributed to the lack of a comprehensive theory of financial regulation to guide policy makers. Existing theories fail to define the range of regulatory models, the causes of regulatory failure, and how to measure and prevent it. Faulty design of regulatory models, and the lack of ongoing performance monitoring incorporating early warning systems, is disrupting economic and social development. The main aim of this article is to propose an early warning system (EWS) which purposes issuing warning signal against the possible financial crisis in the emerging market, and makes the emerging market survived the first wave of the crisis be able to continue their operation in the following years.
Dutt, Arun K
2005-09-22
We have investigated the short-wave instability due to Hopf bifurcation in a reaction-diffusion model of glycolytic oscillations. Very low values of the ratio d of the diffusion coefficient of the inhibitor (ATP) and that of the activator (ADP) do help to create short waves, whereas high values of the ratio d and the complexing reaction of the activator ADP reduces drastically the wave-instability domain, generating much longer wavelengths.
1989-07-01
such as the complex fluid motion over aii irregular bottom and absence of rigorous descriptions of broken waves and sediment-sediment interaction, also...prototype-scale conditions. The tests were carried out with both monochromatic and irregular waves for a dunelike foreshore with and without a...significant surf zone. For one case starting from a beach without "fore- shore," monochromatic waves produced a bar, whereas irregular waves of significant
The noisy edge of traveling waves
Hallatschek, Oskar
2011-01-01
Traveling waves are ubiquitous in nature and control the speed of many important dynamical processes, including chemical reactions, epidemic outbreaks, and biological evolution. Despite their fundamental role in complex systems, traveling waves remain elusive because they are often dominated by rare fluctuations in the wave tip, which have defied any rigorous analysis so far. Here, we show that by adjusting nonlinear model details, noisy traveling waves can be solved exactly. The moment equations of these tuned models are closed and have a simple analytical structure resembling the deterministic approximation supplemented by a nonlocal cutoff term. The peculiar form of the cutoff shapes the noisy edge of traveling waves and is critical for the correct prediction of the wave speed and its fluctuations. Our approach is illustrated and benchmarked using the example of fitness waves arising in simple models of microbial evolution, which are highly sensitive to number fluctuations. We demonstrate explicitly how these models can be tuned to account for finite population sizes and determine how quickly populations adapt as a function of population size and mutation rates. More generally, our method is shown to apply to a broad class of models, in which number fluctuations are generated by branching processes. Because of this versatility, the method of model tuning may serve as a promising route toward unraveling universal properties of complex discrete particle systems. PMID:21187435
Nonlinear dispersion effects in elastic plates: numerical modelling and validation
NASA Astrophysics Data System (ADS)
Kijanka, Piotr; Radecki, Rafal; Packo, Pawel; Staszewski, Wieslaw J.; Uhl, Tadeusz; Leamy, Michael J.
2017-04-01
Nonlinear features of elastic wave propagation have attracted significant attention recently. The particular interest herein relates to complex wave-structure interactions, which provide potential new opportunities for feature discovery and identification in a variety of applications. Due to significant complexity associated with wave propagation in nonlinear media, numerical modeling and simulations are employed to facilitate design and development of new measurement, monitoring and characterization systems. However, since very high spatio- temporal accuracy of numerical models is required, it is critical to evaluate their spectral properties and tune discretization parameters for compromise between accuracy and calculation time. Moreover, nonlinearities in structures give rise to various effects that are not present in linear systems, e.g. wave-wave interactions, higher harmonics generation, synchronism and | recently reported | shifts to dispersion characteristics. This paper discusses local computational model based on a new HYBRID approach for wave propagation in nonlinear media. The proposed approach combines advantages of the Local Interaction Simulation Approach (LISA) and Cellular Automata for Elastodynamics (CAFE). The methods are investigated in the context of their accuracy for predicting nonlinear wavefields, in particular shifts to dispersion characteristics for finite amplitude waves and secondary wavefields. The results are validated against Finite Element (FE) calculations for guided waves in copper plate. Critical modes i.e., modes determining accuracy of a model at given excitation frequency - are identified and guidelines for numerical model parameters are proposed.
Ha, Chang Hoon; Kim, Sunghyen; Chung, Jihwa; An, Shung Hyen; Kwon, Kihwan
2013-10-09
Extracorporeal shock wave has been used in the noninvasive treatment of various diseases including musculoskeletal disorders. In particular, shock wave with low energy level showed anti-inflammatory effect and increased angiogenesis in ischemic tissues. However, the detailed cellular pathway in endothelial signaling is not fully understood. We investigate the role of shock wave with low energy level in angiogenic gene expression and underlying molecular mechanism by comparing the laminar and oscillatory fluid shear stresses in endothelial cells. We show that shock wave with low energy level (0.012-0.045 mJ/mm(2)) stimulated phosphorylation of Akt, eNOS and Erk 1/2 in a time-dependent manner which is similar to the effect of laminar fluid shear stress. The transfection of endothelial cells with siRNA encoding VEGFR2, VE-cadherin and PECAM-1 inhibited shock wave-induced phosphorylation of Akt, eNOS and Erk 1/2 and angiogenic gene expressions, including Akt, eNOS, KLF2/4, and Nur77. Moreover, mechanical stimulation through extracorporeal shock wave induced endothelial cell migration and tube formation. Our results demonstrate that shock wave-induced Akt/eNOS phosphorylation and angiogenic gene expression were mediated through the mechanosensory complex formation involving VEGFR-2, VE-cadherin and PECAM-1 which was similar to the effect of laminar shear stress. © 2013.
Ionic wave propagation and collision in an excitable circuit model of microtubules
NASA Astrophysics Data System (ADS)
Guemkam Ghomsi, P.; Tameh Berinyoh, J. T.; Moukam Kakmeni, F. M.
2018-02-01
In this paper, we report the propensity to excitability of the internal structure of cellular microtubules, modelled as a relatively large one-dimensional spatial array of electrical units with nonlinear resistive features. We propose a model mimicking the dynamics of a large set of such intracellular dynamical entities as an excitable medium. We show that the behavior of such lattices can be described by a complex Ginzburg-Landau equation, which admits several wave solutions, including the plane waves paradigm. A stability analysis of the plane waves solutions of our dynamical system is conducted both analytically and numerically. It is observed that perturbed plane waves will always evolve toward promoting the generation of localized periodic waves trains. These modes include both stationary and travelling spatial excitations. They encompass, on one hand, localized structures such as solitary waves embracing bright solitons, dark solitons, and bisolitonic impulses with head-on collisions phenomena, and on the other hand, the appearance of both spatially homogeneous and spatially inhomogeneous stationary patterns. This ability exhibited by our array of proteinic elements to display several states of excitability exposes their stunning biological and physical complexity and is of high relevance in the description of the developmental and informative processes occurring on the subcellular scale.
Ionic wave propagation and collision in an excitable circuit model of microtubules.
Guemkam Ghomsi, P; Tameh Berinyoh, J T; Moukam Kakmeni, F M
2018-02-01
In this paper, we report the propensity to excitability of the internal structure of cellular microtubules, modelled as a relatively large one-dimensional spatial array of electrical units with nonlinear resistive features. We propose a model mimicking the dynamics of a large set of such intracellular dynamical entities as an excitable medium. We show that the behavior of such lattices can be described by a complex Ginzburg-Landau equation, which admits several wave solutions, including the plane waves paradigm. A stability analysis of the plane waves solutions of our dynamical system is conducted both analytically and numerically. It is observed that perturbed plane waves will always evolve toward promoting the generation of localized periodic waves trains. These modes include both stationary and travelling spatial excitations. They encompass, on one hand, localized structures such as solitary waves embracing bright solitons, dark solitons, and bisolitonic impulses with head-on collisions phenomena, and on the other hand, the appearance of both spatially homogeneous and spatially inhomogeneous stationary patterns. This ability exhibited by our array of proteinic elements to display several states of excitability exposes their stunning biological and physical complexity and is of high relevance in the description of the developmental and informative processes occurring on the subcellular scale.
Design and performance of optimal detectors for guided wave structural health monitoring
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dib, G.; Udpa, L.
2016-01-01
Ultrasonic guided wave measurements in a long term structural health monitoring system are affected by measurement noise, environmental conditions, transducer aging and malfunction. This results in measurement variability which affects detection performance, especially in complex structures where baseline data comparison is required. This paper derives the optimal detector structure, within the framework of detection theory, where a guided wave signal at the sensor is represented by a single feature value that can be used for comparison with a threshold. Three different types of detectors are derived depending on the underlying structure’s complexity: (i) Simple structures where defect reflections can bemore » identified without the need for baseline data; (ii) Simple structures that require baseline data due to overlap of defect scatter with scatter from structural features; (iii) Complex structure with dense structural features that require baseline data. The detectors are derived by modeling the effects of variabilities and uncertainties as random processes. Analytical solutions for the performance of detectors in terms of the probability of detection and false alarm are derived. A finite element model is used to generate guided wave signals and the performance results of a Monte-Carlo simulation are compared with the theoretical performance. initial results demonstrate that the problems of signal complexity and environmental variability can in fact be exploited to improve detection performance.« less
Excited-state vibronic wave-packet dynamics in H2 probed by XUV transient four-wave mixing
NASA Astrophysics Data System (ADS)
Cao, Wei; Warrick, Erika R.; Fidler, Ashley; Leone, Stephen R.; Neumark, Daniel M.
2018-02-01
The complex behavior of a molecular wave packet initiated by an extreme ultraviolet (XUV) pulse is investigated with noncollinear wave mixing spectroscopy. A broadband XUV pulse spanning 12-16 eV launches a wave packet in H2 comprising a coherent superposition of multiple electronic and vibrational levels. The molecular wave packet evolves freely until a delayed few-cycle optical laser pulse arrives to induce nonlinear signals in the XUV via four-wave mixing (FWM). The angularly resolved FWM signals encode rich energy exchange processes between the optical laser field and the XUV-excited molecule. The noncollinear geometry enables spatial separation of ladder and V- or Λ-type transitions induced by the optical field. Ladder transitions, in which the energy exchange with the optical field is around 3 eV, appear off axis from the incident XUV beam. Each vibrationally revolved FWM line probes a different part of the wave packet in energy, serving as a promising tool for energetic tomography of molecular wave packets. V- or Λ-type transitions, in which the energy exchange is well under 1 eV, result in on-axis nonlinear signals. The first-order versus third-order interference of the on-axis signal serves as a mapping tool of the energy flow pathways. Intra- and interelectronic potential energy curve transitions are decisively identified. The current study opens possibilities for accessing complete dynamic information in XUV-excited complex systems.
Electrocardiogram Changes with Acute Alcohol Intoxication: A Systematic Review.
Raheja, Hitesh; Namana, Vinod; Chopra, Kirti; Sinha, Ankur; Gupta, Sushilkumar Satish; Kamholz, Stephan; Moskovits, Norbert; Shani, Jacob; Hollander, Gerald
2018-01-01
Acute alcohol intoxication has been associated with cardiac arrhythmias but the electrocardiogram (ECG) changes associated with acute alcohol intoxication are not well defined in the literature. Highlight the best evidence regarding the ECG changes associated with acute alcohol intoxication in otherwise healthy patients and the pathophysiology of the changes. A literature search was carried out; 4 studies relating to ECG changes with acute alcohol intoxication were included in this review. Of the total 141 patients included in the review, 90 (63.8%) patients had P-wave prolongation, 80 (56%) patients had QTc prolongation, 19 (13.5%) patients developed T-wave abnormalities, 10 (7%) patients had QRS complex prolongation, 3 (2.12%) patients developed ST-segment depressions. The most common ECG changes associated with acute alcohol intoxication are (in decreasing order of frequency) P-wave and QTc prolongation, followed by T-wave abnormalities and QRS complex prolongation. Mostly, these changes are completely reversible.
Lamb wave propagation in a restricted geometry composite pi-joint specimen
NASA Astrophysics Data System (ADS)
Blackshire, James L.; Soni, Som
2012-05-01
The propagation of elastic waves in a material can involve a number of complex physical phenomena, resulting in both subtle and dramatic effects on detected signal content. In recent years, the use of advanced methods for characterizing and imaging elastic wave propagation and scattering processes has increased, where for example the use of scanning laser vibrometry and advanced computational models have been used very effectively to identify propagating modes, scattering phenomena, and damage feature interactions. In the present effort, the propagation of Lamb waves within a narrow, constrained geometry composite pi-joint structure are studied using 3D finite element models and scanning laser vibrometry measurements, where the effects of varying sample thickness, complex joint curvatures, and restricted structure geometries are highlighted, and a direct comparison of computational and experimental results are provided for simulated and realistic geometry composite pi-joint samples.
New method for rekindling the nonlinear solitary waves in Maxwellian complex space plasma
NASA Astrophysics Data System (ADS)
Das, G. C.; Sarma, Ridip
2018-04-01
Our interest is to study the nonlinear wave phenomena in complex plasma constituents with Maxwellian electrons and ions. The main reason for this consideration is to exhibit the effects of dust charge fluctuations on acoustic modes evaluated by the use of a new method. A special method (G'/G) has been developed to yield the coherent features of nonlinear waves augmented through the derivation of a Korteweg-de Vries equation and found successfully the different nature of solitons recognized in space plasmas. Evolutions have shown with the input of appropriate typical plasma parameters to support our theoretical observations in space plasmas. All conclusions are in good accordance with the actual occurrences and could be of interest to further the investigations in experiments and satellite observations in space. In this paper, we present not only the model that exhibited nonlinear solitary wave propagation but also a new mathematical method to the execution.
NASA Astrophysics Data System (ADS)
Mixa, T.; Fritts, D. C.; Bossert, K.; Laughman, B.; Wang, L.; Lund, T.; Kantha, L. H.
2017-12-01
Gravity waves play a profound role in the mixing of the atmosphere, transporting vast amounts of momentum and energy among different altitudes as they propagate vertically. Above 60km in the middle atmosphere, high wave amplitudes enable a series of complex, nonlinear interactions with the background environment that produce highly-localized wind and temperature variations which alter the layering structure of the atmosphere. These small-scale interactions account for a significant portion of energy transport in the middle atmosphere, but they are difficult to characterize, occurring at spatial scales that are both challenging to observe with ground instruments and prohibitively small to include in weather forecasting models. Using high fidelity numerical simulations, these nuanced wave interactions are analyzed to better our understanding of these dynamics and improve the accuracy of long-term weather forecasting.
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AP1 Keeps Chromatin Poised for Action | Center for Cancer Research
The human genome harbors gene-encoding DNA, the blueprint for building proteins that regulate cellular function. Embedded across the genome, in non-coding regions, are DNA elements to which regulatory factors bind. The interaction of regulatory factors with DNA at these sites modifies gene expression to modulate cell activity. In cells, DNA exists in a complex with proteins
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Steering healthcare service delivery: a regulatory perspective.
Prakash, Gyan
2015-01-01
The purpose of this paper is to explore regulation in India's healthcare sector and makes recommendations needed for enhancing the healthcare service. The literature was reviewed to understand healthcare's regulatory context. To understand the current healthcare system, qualitative data were collected from state-level officials, public and private hospital staff. A patient survey was performed to assess service quality (QoS). Regulation plays a central role in driving healthcare QoS. India needs to strengthen market and institutional co-production based approaches for steering its healthcare in which delivery processes are complex and pose different challenges. This study assesses current healthcare regulation in an Indian state and presents a framework for studying and strengthening regulation. Agile regulation should be based on service delivery issues (pull approach) rather than monitoring and sanctions based regulatory environment (push approach). Healthcare pitfalls across the world seem to follow similar follies. India's complexity and experience is useful for emerging and developed economies. The author reviewed around 70 publications and synthesised them in healthcare regulatory contexts. Patient's perception of private providers could be a key input towards steering regulation. Identifying gaps across QoS dimensions would be useful in taking corrective measures.
About the role of the source terms on the spatial structure of the wave field in hurricanes
NASA Astrophysics Data System (ADS)
Osuna, P.; Esquivel-Trava, B.; Ocampo-Torres, F. J.
2012-04-01
A numerical experiment has been carried out in order to study the structure of the wave field during hurricane conditions. High resolution wind data for a hurricane were obtained by the use of a Holland type asymmetric model. The third generation wind-wave model SWAN has been used in this study. A reference framework for the structure of the wave field in hurricanes is obtained using the NDBC directional buoy database in the Caribbean Sea and the Gulf of Mexico. This observational reference is used to assess the ability of the model to reproduce the complexity of the wave field observed in hurricanes. It is found that the numerical results are in good agreement with the observed wave field in the hurricane: higher waves are in the right forward quadrant of the hurricane, where the spectral shape tends to become uni-modal. More complex spectral shapes are observed in the rear quadrants of the hurricane, where a tendency of the spectra to become multi-modal is observed. As pointed out by other authors, the wave field in the hurricane is dominated by swell propagating at significant angles to the local wind directions, except on a small region between the first and fourth quadrants. A deeper insight on the role of the physics that controls the evolution of the wave field is assessed by the analysis of the effect of the source terms computed by the wave model in the four quadrants of the hurricane. This is a contribution to the project CB-168173, funded by CONACYT.
Transonic Shock-Wave/Boundary-Layer Interactions on an Oscillating Airfoil
NASA Technical Reports Server (NTRS)
Davis, Sanford S.; Malcolm, Gerald N.
1980-01-01
Unsteady aerodynamic loads were measured on an oscillating NACA 64A010 airfoil In the NASA Ames 11 by 11 ft Transonic Wind Tunnel. Data are presented to show the effect of the unsteady shock-wave/boundary-layer interaction on the fundamental frequency lift, moment, and pressure distributions. The data show that weak shock waves induce an unsteady pressure distribution that can be predicted quite well, while stronger shock waves cause complex frequency-dependent distributions due to flow separation. An experimental test of the principles of linearity and superposition showed that they hold for weak shock waves while flows with stronger shock waves cannot be superimposed.
Major dust storms and westward traveling waves on Mars
NASA Astrophysics Data System (ADS)
Wang, Huiqun
2017-04-01
Westward traveling waves are observed during major dust storm periods in northern fall and winter. The close correlation in timing makes westward traveling wave one of the signature responses of the Martian atmosphere to major dust storms. Westward traveling waves are dominated by zonal wave number m = 1 in the middle atmosphere and are typically characterized by long wave period. They are associated with significant temperature perturbations near the edge of the north polar vortex. Their wind signals extend to the low latitudes and the southern hemisphere. Their eddy momentum and heat fluxes exhibit complex patterns on a global scale in the middle atmosphere.
Pattern masking: the importance of remote spatial frequencies and their phase alignment.
Huang, Pi-Chun; Maehara, Goro; May, Keith A; Hess, Robert F
2012-02-16
To assess the effects of spatial frequency and phase alignment of mask components in pattern masking, target threshold vs. mask contrast (TvC) functions for a sine-wave grating (S) target were measured for five types of mask: a sine-wave grating (S), a square-wave grating (Q), a missing fundamental square-wave grating (M), harmonic complexes consisting of phase-scrambled harmonics of a square wave (Qp), and harmonic complexes consisting of phase-scrambled harmonics of a missing fundamental square wave (Mp). Target and masks had the same fundamental frequency (0.46 cpd) and the target was added in phase with the fundamental frequency component of the mask. Under monocular viewing conditions, the strength of masking depends on phase relationships among mask spatial frequencies far removed from that of the target, at least 3 times the target frequency, only when there are common target and mask spatial frequencies. Under dichoptic viewing conditions, S and Q masks produced similar masking to each other and the phase-scrambled masks (Qp and Mp) produced less masking. The results suggest that pattern masking is spatial frequency broadband in nature and sensitive to the phase alignments of spatial components.
Baseline-Subtraction-Free (BSF) Damage-Scattered Wave Extraction for Stiffened Isotropic Plates
NASA Technical Reports Server (NTRS)
He, Jiaze; Leser, Patrick E.; Leser, William P.
2017-01-01
Lamb waves enable long distance inspection of structures for health monitoring purposes. However, this capability is diminished when applied to complex structures where damage-scattered waves are often buried by scattering from various structural components or boundaries in the time-space domain. Here, a baseline-subtraction-free (BSF) inspection concept based on the Radon transform (RT) is proposed to identify and separate these scattered waves from those scattered by damage. The received time-space domain signals can be converted into the Radon domain, in which the scattered signals from structural components are suppressed into relatively small regions such that damage-scattered signals can be identified and extracted. In this study, a piezoelectric wafer and a linear scan via laser Doppler vibrometer (LDV) were used to excite and acquire the Lamb-wave signals in an aluminum plate with multiple stiffeners. Linear and inverse linear Radon transform algorithms were applied to the direct measurements. The results demonstrate the effectiveness of the Radon transform as a reliable extraction tool for damage-scattered waves in a stiffened aluminum plate and also suggest the possibility of generalizing this technique for application to a wide variety of complex, large-area structures.
Hourd, Paul; Medcalf, Nicholas; Segal, Joel; Williams, David J
2015-01-01
Computer-aided 3D printing approaches to the industrial production of customized 3D functional living constructs for restoration of tissue and organ function face significant regulatory challenges. Using the manufacture of a customized, 3D-bioprinted nasal implant as a well-informed but hypothetical exemplar, we examine how these products might be regulated. Existing EU and USA regulatory frameworks do not account for the differences between 3D printing and conventional manufacturing methods or the ability to create individual customized products using mechanized rather than craft approaches. Already subject to extensive regulatory control, issues related to control of the computer-aided design to manufacture process and the associated software system chain present additional scientific and regulatory challenges for manufacturers of these complex 3D-bioprinted advanced combination products.
From Genes to Networks: Characterizing Gene-Regulatory Interactions in Plants.
Kaufmann, Kerstin; Chen, Dijun
2017-01-01
Plants, like other eukaryotes, have evolved complex mechanisms to coordinate gene expression during development, environmental response, and cellular homeostasis. Transcription factors (TFs), accompanied by basic cofactors and posttranscriptional regulators, are key players in gene-regulatory networks (GRNs). The coordinated control of gene activity is achieved by the interplay of these factors and by physical interactions between TFs and DNA. Here, we will briefly outline recent technological progress made to elucidate GRNs in plants. We will focus on techniques that allow us to characterize physical interactions in GRNs in plants and to analyze their regulatory consequences. Targeted manipulation allows us to test the relevance of specific gene-regulatory interactions. The combination of genome-wide experimental approaches with mathematical modeling allows us to get deeper insights into key-regulatory interactions and combinatorial control of important processes in plants.
NASA Astrophysics Data System (ADS)
Hu, Yanpu; Egbert, Gary; Ji, Yanju; Fang, Guangyou
2017-01-01
In this study, we apply fictitious wave domain (FWD) methods, based on the correspondence principle for the wave and diffusion fields, to finite difference (FD) modeling of transient electromagnetic (TEM) diffusion problems for geophysical applications. A novel complex frequency shifted perfectly matched layer (PML) boundary condition is adapted to the FWD to truncate the computational domain, with the maximum electromagnetic wave propagation velocity in the FWD used to set the absorbing parameters for the boundary layers. Using domains of varying spatial extent we demonstrate that these boundary conditions offer significant improvements over simpler PML approaches, which can result in spurious reflections and large errors in the FWD solutions, especially for low frequencies and late times. In our development, resistive air layers are directly included in the FWD, allowing simulation of TEM responses in the presence of topography, as is commonly encountered in geophysical applications. We compare responses obtained by our new FD-FWD approach and with the spectral Lanczos decomposition method on 3-D resistivity models of varying complexity. The comparisons demonstrate that our absorbing boundary condition in FWD for the TEM diffusion problems works well even in complex high-contrast conductivity models.
Enhancement of branching efficiency by the actin filament-binding activity of N-WASP/WAVE2.
Suetsugu, S; Miki, H; Yamaguchi, H; Obinata, T; Takenawa, T
2001-12-01
The actin-related protein (Arp) 2/3 complex is an essential regulator of de novo actin filament formation. Arp2/3 nucleates the polymerization of actin and creates branched actin filaments when activated by Arp2/3-complex activating domain (VCA) of Wiskott-Aldrich syndrome proteins (WASP family proteins). We found that the branching of actin filaments on pre-existing ADP filaments mediated by the Arp2/3 complex is twice as efficient when Arp2/3 was activated by wild-type neural WASP (N-WASP) or WASP-family verprolin-homologous protein (WAVE) 2 than when activated by the VCA domain alone. By contrast, there was no difference between wild-type N-WASP or WAVE2 and VCA in the branching efficiency on de novo filaments, which are thought to consist mainly of ADP-phosphate filaments. This increased branching efficiency on ADP filaments is due to the basic region located in the center of N-WASP and WAVE2, which was found to associate with ADP actin filaments. Actin filaments and phosphatidylinositol bisphosphate (PIP2) associate with N-WASP at different sites. This association of N-WASP and WAVE2 with actin filaments enhanced recruitment of Arp2/3 to the pre-existing filaments, presumably leading to efficient nucleation and branch formation on pre-existing filaments. These data together suggest that the actin filament binding activity of N-WASP and WAVE2 in the basic region increases the number of barbed ends created on pre-existing filaments. Efficient branching on ADP filaments may be important for initiation of actin-based motility.
Mern, Demissew S; Ha, Seung-Wook; Khodaverdi, Viola; Gliese, Nicole; Görisch, Helmut
2010-05-01
In addition to the known response regulator ErbR (former AgmR) and the two-component regulatory system EraSR (former ExaDE), three additional regulatory proteins have been identified as being involved in controlling transcription of the aerobic ethanol oxidation system in Pseudomonas aeruginosa. Two putative sensor kinases, ErcS and ErcS', and a response regulator, ErdR, were found, all of which show significant similarity to the two-component flhSR system that controls methanol and formaldehyde metabolism in Paracoccus denitrificans. All three identified response regulators, EraR (formerly ExaE), ErbR (formerly AgmR) and ErdR, are members of the luxR family. The three sensor kinases EraS (formerly ExaD), ErcS and ErcS' do not contain a membrane domain. Apparently, they are localized in the cytoplasm and recognize cytoplasmic signals. Inactivation of gene ercS caused an extended lag phase on ethanol. Inactivation of both genes, ercS and ercS', resulted in no growth at all on ethanol, as did inactivation of erdR. Of the three sensor kinases and three response regulators identified thus far, only the EraSR (formerly ExaDE) system forms a corresponding kinase/regulator pair. Using reporter gene constructs of all identified regulatory genes in different mutants allowed the hierarchy of a hypothetical complex regulatory network to be established. Probably, two additional sensor kinases and two additional response regulators, which are hidden among the numerous regulatory genes annotated in the genome of P. aeruginosa, remain to be identified.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Svintradze, David V.; Virginia Commonwealth University, Richmond, VA 23219-1540; Peterson, Darrell L.
Differences in OxyR regulated expression of oxidative stress genes between Escherichia coli and Porphyromonas gingivalis are explained by very minor differences in structure and amino-acid sequence of the respective oxidized and reduced OxyR regulatory domains. These differences affect OxyR quaternary structures and are predicted from model building of full length OxyR–DNA complexes to confer distinct modes of DNA binding on this transcriptional regulator. OxyR transcriptionally regulates Escherichia coli oxidative stress response genes through a reversibly reducible cysteine disulfide biosensor of cellular redox status. Structural changes induced by redox changes in these cysteines are conformationally transmitted to the dimer subunit interfaces,more » which alters dimer and tetramer interactions with DNA. In contrast to E. coli OxyR regulatory-domain structures, crystal structures of Porphyromonas gingivalis OxyR regulatory domains show minimal differences in dimer configuration on changes in cysteine disulfide redox status. This locked configuration of the P. gingivalis OxyR regulatory-domain dimer closely resembles the oxidized (activating) form of the E. coli OxyR regulatory-domain dimer. It correlates with the observed constitutive activation of some oxidative stress genes in P. gingivalis and is attributable to a single amino-acid insertion in P. gingivalis OxyR relative to E. coli OxyR. Modelling of full-length P. gingivalis, E. coli and Neisseria meningitidis OxyR–DNA complexes predicts different modes of DNA binding for the reduced and oxidized forms of each.« less
The quasi-6 day wave and its interactions with solar tides
NASA Astrophysics Data System (ADS)
Forbes, Jeffrey M.; Zhang, Xiaoli
2017-04-01
Thermosphere Ionosphere Mesosphere Energetics and Dynamics/Sounding of the Atmosphere using Broadband Emission Radiometry (TIMED/SABER) temperature measurements between 20 and 110 km altitude and ±50° latitude during 2002-2015 are employed to reveal the climatological characteristics of the quasi-6 day wave (Q6DW) and evidence for secondary waves (SW) resulting from its nonlinear interactions with solar tides. The mean period is 6.14d with a standard deviation (σ) of 0.26d. Multiyear-mean maximum amplitudes (3-5 K, σ ˜ 4 K) occur within the mesosphere-lower thermosphere (MLT) region between 75 and 100 km during day of year (DOY) 60-120 and 180-300 in the Northern Hemisphere and DOY 0-110 and 200-300 in the Southern Hemisphere. Amplitudes approach 10 K in some individual years. At midlatitudes downward phase progression exists from 100 to 35 km with a mean vertical wavelength of about 70 km. Signatures of SW due to Q6DW-tide interactions appear at distinct space-based zonal wave numbers (ks) in temperature spectra constructed in the reference frame of the TIMED orbit. However, SW produced by several different tides can collapse onto the same (ks) value, rendering their relative contributions indistinguishable. Nevertheless, by determining the space-based wave amplitudes attached to these values of (ks), and demonstrating that they are a large fraction of the interacting wave amplitudes, we conclude that the aggregate contributions of the SW to the overall wave spectrum must be significant. Because the SW have periods, zonal wave numbers, and latitude-height structures different from those of the primary waves, they contribute additionally to the complexity of the wave spectrum. This complexity is communicated to the ionosphere through collisions or through the dynamo electric fields generated by the total wave spectrum.
NASA Astrophysics Data System (ADS)
Brodie, Katherine L.
Elevated water levels and large waves during storms cause beach erosion, overwash, and coastal flooding, particularly along barrier island coastlines. While predictions of storm tracks have greatly improved over the last decade, predictions of maximum water levels and variations in the extent of damage along a coastline need improvement. In particular, physics based models still cannot explain why some regions along a relatively straight coastline may experience significant erosion and overwash during a storm, while nearby locations remain seemingly unchanged. Correct predictions of both the timing of erosion and variations in the magnitude of erosion along the coast will be useful to both emergency managers and homeowners preparing for an approaching storm. Unfortunately, research on the impact of a storm to the beach has mainly been derived from "pre" and "post" storm surveys of beach topography and nearshore bathymetry during calm conditions. This has created a lack of data during storms from which to ground-truth model predictions and test hypotheses that explain variations in erosion along a coastline. We have developed Coastal Lidar and Radar Imaging System (CLARIS), a mobile system that combines a terrestrial scanning laser and an X-band marine radar system using precise motion and location information. CLARIS can operate during storms, measuring beach topography, nearshore bathymetry (from radar-derived wave speed measurements), surf-zone wave parameters, and maximum water levels remotely. In this dissertation, we present details on the development, design, and testing of CLARIS and then use CLARIS to observe a 10 km section of coastline in Kitty Hawk and Kill Devil Hills on the Outer Banks of North Carolina every 12 hours during a Nor'Easter (peak wave height in 8 m of water depth = 3.4 m). High decadal rates of shoreline change as well as heightened erosion during storms have previously been documented to occur within the field site. In addition, complex bathymetric features that traverse the surf-zone into the nearshore are present along the southern six kilometers of the field site. In addition to the CLARIS observations, we model wave propagation over the complex nearshore bathymetry for the same storm event. Data reveal that the complex nearshore bathymetry is mirrored by kilometer scale undulations in the shoreline, and that both morphologies persist during storms, contrary to common observations of shoreline and surf-zone linearization by large storm waves. We hypothesize that wave refraction over the complex nearshore bathymetry forces flow patterns which may enhance or stabilize the shoreline and surf-zone morphology during storms. In addition, our semi-daily surveys of the beach indicate that spatial and temporal patterns of erosion are strongly correlated to the steepness of the waves. Along more than half the study site, fifty percent or more of the erosion that occurred during the first 12 hours of the storm was recovered within 24 hours of the peak of the storm as waves remained large (>2.5 m), but transitioned to long period swell. In addition, spatial variations in the amount of beach volume change during the building portion of the storm were strongly correlated with observed wave dissipation within the inner surf zone, as opposed to predicted inundation elevations or alongshore variations in wave height.
Dynamic Control of Excitatory Synapse Development by a Rac1 GEF/GAP Regulatory Complex
Um, Kyongmi; Niu, Sanyong; Duman, Joseph G.; Cheng, Jinxuan; Tu, Yen-Kuei; Schwechter, Brandon; Liu, Feng; Hiles, Laura; Narayanan, Anjana; Ash, Ryan T.; Mulherkar, Shalaka; Alpadi, Kannan; Smirnakis, Stelios M.; Tolias, Kimberley F.
2014-01-01
SUMMARY The small GTPase Rac1 orchestrates actin-dependent remodeling essential for numerous cellular processes including synapse development. While precise spatiotemporal regulation of Rac1 is necessary for its function, little is known about the mechanisms that enable Rac1 activators (GEFs) and inhibitors (GAPs) to act in concert to regulate Rac1 signaling. Here we identify a regulatory complex composed of a Rac-GEF (Tiam1) and a Rac-GAP (Bcr) that cooperate to control excitatory synapse development. Disruption of Bcr function within this complex increases Rac1 activity and dendritic spine remodeling, resulting in excessive synaptic growth that is rescued by Tiam1 inhibition. Notably, EphB receptors utilize the Tiam1-Bcr complex to control synaptogenesis. Following EphB activation, Tiam1 induces Rac1-dependent spine formation, whereas Bcr prevents Rac1-mediated receptor internalization, promoting spine growth over retraction. The finding that a Rac-specific GEF/GAP complex is required to maintain optimal levels of Rac1 signaling provides an important insight into the regulation of small GTPases. PMID:24960694
Guitar Strings as Standing Waves: A Demonstration
ERIC Educational Resources Information Center
Davis, Michael
2007-01-01
The study demonstrates the induction of one-dimensional standing waves, called "natural-harmonics" on a guitar to provide a unique tone. The analysis shows that a normally complex vibration is composed of a number of simple and discrete vibrations.
Surface Roughness Measurements Utilizing Long-Range Surface-Plasma Waves
1984-11-01
8217 The theory dealt only with the depen- modes, one symmetric and one antisymmetric, dence of the real wave vector on the real part of that propagate...quantity, while the wave vector is complex. It is shown that for both the supported and unsup- From Eqs. (1) and (2) one obtains the real implic- ported...Opt. Soc. sabbatical leave from the University of Toledo. Am.). Optical feild enhancemeft by long-range surface- I" ouT In O’ in OUT way@, plasma waves
Bending self-collimated one-way light by using gyromagnetic photonic crystals
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, Qing-Bo; Jiangsu Key Construction Laboratory of Modern Measurement Technology and Intelligent System, Huaiyin Normal University, Huaian 223300; Li, Zhen
2015-12-14
We theoretically demonstrate that electromagnetic waves can self-collimate and propagate unidirectionally in photonic crystals fabricated using semicylindrical ferrite rods in magnetized states. The parity and time-reversal symmetries of such photonic crystals are broken, resulting in a self-collimated one-way body wave within the photonic crystals. By applying the bias magnetic field in a complex configuration, the self-collimated one-way wave beam can be bent into arbitrary trajectories within the photonic crystal, providing an avenue for controlling wave beams.
Insulin stimulates syntaxin4 SNARE complex assembly via a novel regulatory mechanism.
Kioumourtzoglou, Dimitrios; Gould, Gwyn W; Bryant, Nia J
2014-04-01
Insulin stimulates glucose transport into fat and muscle cells by increasing the exocytic trafficking rate of the GLUT4 facilitative glucose transporter from intracellular stores to the plasma membrane. Delivery of GLUT4 to the plasma membrane is mediated by formation of functional SNARE complexes containing syntaxin4, SNAP23, and VAMP2. Here we have used an in situ proximity ligation assay to integrate these two observations by demonstrating for the first time that insulin stimulation causes an increase in syntaxin4-containing SNARE complex formation in adipocytes. Furthermore, we demonstrate that insulin brings about this increase in SNARE complex formation by mobilizing a pool of syntaxin4 held in an inactive state under basal conditions. Finally, we have identified phosphorylation of the regulatory protein Munc18c, a direct target of the insulin receptor, as a molecular switch to coordinate this process. Hence, this report provides molecular detail of how the cell alters membrane traffic in response to an external stimulus, in this case, insulin.
Methylation-regulated decommissioning of multimeric PP2A complexes
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wu, Cheng-Guo; Zheng, Aiping; Jiang, Li
2017-12-01
Dynamic assembly/disassembly of signaling complexes are crucial for cellular functions. Specialized latency and activation chaperones control the biogenesis of protein phosphatase 2A (PP2A) holoenzymes that contain a common scaffold and catalytic subunits and a variable regulatory subunit. Here we show that the butterfly-shaped TIPRL (TOR signaling pathway regulator) makes highly integrative multibranching contacts with the PP2A catalytic subunit, selective for the unmethylated tail and perturbing/inactivating the phosphatase active site. TIPRL also makes unusual wobble contacts with the scaffold subunit, allowing TIPRL, but not the overlapping regulatory subunits, to tolerate disease-associated PP2A mutations, resulting in reduced holoenzyme assembly and enhanced inactivationmore » of mutant PP2A. Strikingly, TIPRL and the latency chaperone, α4, coordinate to disassemble active holoenzymes into latent PP2A, strictly controlled by methylation. Our study reveals a mechanism for methylation-responsive inactivation and holoenzyme disassembly, illustrating the complexity of regulation/signaling, dynamic complex disassembly, and disease mutations in cancer and intellectual disability.« less
An innovative early warning system for floods and operational risks in harbours
NASA Astrophysics Data System (ADS)
Smets, Steven; Bolle, Annelies; Mollaert, Justine; Buitrago, Saul; Gruwez, Vincent
2016-04-01
Early Warning Systems (EWS) are nowadays becoming fairly standard in river flood forecasting or in large scale hydrometeorological predictions. For complex coastal morphodynamic problems or in the vicinity of complex coastal structures, such as harbours, EWS are much less used because they are both technically and computationally still very challenging. To advance beyond the state-of-the-art, the EU FP7 project Risc-KIT (www.risc-kit.eu) is developing prototype EWS which address specifically these topics. This paper describes the prototype EWS which IMDC has developed for the case study site of the harbour of Zeebrugge. The harbour of Zeebrugge is the largest industrial seaport on the coast of Belgium, extending more than 3 km into the sea. Two long breakwaters provide shelter for the inner quays and docks for regular conditions and frequent storms. Extreme storms surges and waves can however still enter the harbour and create risks for the harbour operations and infrastructure. The prediction of the effects of storm surges and waves inside harbours are typically very complex and challenging, due to the need of different types of numerical models for representing all different physical processes. In general, waves inside harbours are a combination of locally wind generated waves and offshore wave penetration at the port entrance. During extreme conditions, the waves could overtop the quays and breakwaters and flood the port facilities. Outside a prediction environment, the conditions inside the harbour could be assessed by superimposing processes. The assessment can be carried out by using a combination of a spectral wave model (i.e. SWAN) for the wind generated waves and a Boussinesq type wave model (i.e. Mike 21 BW) for the wave penetration from offshore. Finally, a 2D hydrodynamic model (i.e. TELEMAC) can be used to simulate the overland flooding inside the port facilities. To reproduce these processes in an EWS environment, an additional challenge is to cope with the limitations of the calculation engines. This is especially true with the Boussinesq model. A model train is proposed that integrates processed based modelling, for wind generated waves, with an intelligent simplification of the Boussinesq model for the wave penetration effects. These wave conditions together with the extreme water levels (including storm surge) can then be used to simulate the overtopping/overflow behaviour for the quays. Finally, the hydrodynamic model TELEMAC is run for the inundation forecast inside the port facilities. The complete model train was integrated into the Deltares Delft FEWS software to showcase the potential for real time operations.
Methodology and evaluation of intracranial pressure response in rats exposed to complex shock waves.
Dal Cengio Leonardi, Alessandra; Keane, Nickolas J; Hay, Kathryn; Ryan, Anne G; Bir, Cynthia A; VandeVord, Pamela J
2013-12-01
Studies on blast neurotrauma have focused on investigating the effects of exposure to free-field blast representing the simplest form of blast threat scenario without considering any reflecting surfaces. However, in reality personnel are often located within enclosures or nearby reflecting walls causing a complex blast environment, that is, involving shock reflections and/or compound waves from different directions. The purpose of this study was to design a complex wave testing system and perform a preliminary investigation of the intracranial pressure (ICP) response of rats exposed to a complex blast wave environment (CBWE). The effects of head orientation in the same environment were also explored. Furthermore, since it is hypothesized that exposure to a CBWE would be more injurious as compared to a free-field blast wave environment (FFBWE), a histological comparison of hippocampal injury (cleaved caspase-3 and glial fibrillary acidic protein (GFAP)) was conducted in both environments. Results demonstrated that, regardless of orientation, peak ICP values were significantly elevated over the peak static air overpressure. Qualitative differences could be noticed compared to the ICP response in rats exposed to simulated FFBWE. In the CBWE scenario, after the initial loading the skull/brain system was not allowed to return to rest and was loaded again reaching high ICP values. Furthermore, results indicated consistent and distinct ICP-time profiles according to orientation, as well as distinctive values of impulse associated with each orientation. Histologically, cleaved caspase-3 positive cells were significantly increased in the CBWE as compared to the FFBWE. Overall, these findings suggest that the geometry of the skull and the way sutures are distributed in the rats are responsible for the difference in the stresses observed. Moreover, this increase stress contributes to correlation of increased injury in the CBWE.
Sound-Induced Intracellular Ca2+ Dynamics in the Adult Hearing Cochlea
Chan, Dylan K.; Rouse, Stephanie L.
2016-01-01
Ca2+ signaling has been implicated in the initial pathophysiologic mechanisms underlying the cochlea's response to acoustic overstimulation. Intracellular Ca2+ signaling (ICS) waves, which occur in glia and retinal cells in response to injury to activate cell regulatory pathways, have been proposed as an early event in cochlear injury. Disruption of ICS activity is thought to underlie Connexin 26-associated hearing loss, the most common genetic form of deafness, and downstream sequelae of ICS wave activity, such as MAP kinase pathway activation, have been implicated in noise-induced hearing loss. However, ICS waves have only been observed in neonatal cochlear cultures and are thought to be quiescent after the onset of hearing. In this study, we employ an acute explant model of an adult, hearing cochlea that retains many in vivo physiologic features to investigate Ca2+ changes in response to sound. We find that both slow monotonic changes in intracellular Ca2+ concentration as well as discrete ICS waves occur with acoustic overstimulation. The ICS waves share many intrinsic features with their better-described neonatal counterparts, including ATP and gap-junction dependence, and propagation velocity and distance. This identification of ICS wave activity in the adult, hearing cochlea thus confirms and characterizes an important early detection mechanism for cochlear trauma and provides a target for interventions for noise-induced and Connexin 26-associated hearing loss. PMID:27959894
A pitfall in shallow shear-wave refraction surveying
Xia, J.; Miller, R.D.; Park, C.B.; Wightman, E.; Nigbor, R.
2002-01-01
The shallow shear-wave refraction method works successfully in an area with a series of horizontal layers. However, complex near-surface geology may not fit into the assumption of a series of horizontal layers. That a plane SH-wave undergoes wave-type conversion along an interface in an area of nonhorizontal layers is theoretically inevitable. One real example shows that the shallow shear-wave refraction method provides velocities of a converted wave rather than an SH- wave. Moreover, it is impossible to identify the converted wave by refraction data itself. As most geophysical engineering firms have limited resources, an additional P-wave refraction survey is necessary to verify if velocities calculated from a shear-wave refraction survey are velocities of converted waves. The alternative at this time may be the surface wave method, which can provide reliable S-wave velocities, even in an area of velocity inversion (a higher velocity layer underlain by a lower velocity layer). ?? 2002 Elsevier Science B.V. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Vanroose, W.; Broeckhove, J.; Arickx, F.
The paper proposes a hybrid method for calculating scattering processes. It combines the J-matrix method with exterior complex scaling and an absorbing boundary condition. The wave function is represented as a finite sum of oscillator eigenstates in the inner region, and it is discretized on a grid in the outer region. The method is validated for a one- and a two-dimensional model with partial wave equations and a calculation of p-shell nuclear scattering with semirealistic interactions.
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Theoretical approximation of focusing-wave induced load upon a large-scale vertical cylinder
NASA Astrophysics Data System (ADS)
Xue, Hong-xiang; Hu, Zhe; Tang, Wen-yong; Zhang, Xiao-ying; Wang, Kun-peng
2017-10-01
Until now, most researches into the rogue-wave-structure interaction have relied on experimental measurement and numerical simulation. Owing to the complexity of the physical mechanism of rogue waves, theoretical study on the wave-structure issue still makes little progress. In this paper, the rogue wave flow around a vertical cylinder is analytically studied within the scope of the potential theory. The rogue wave is modeled by the Gauss envelope, which is one particular case of the well-known focusing theory. The formulae of the wave-induced horizontal force and bending moment are proposed. For the convenience of engineering application, the derived formulae are simplified appropriately, and verified against numerical results. In addition, the influence of wave parameters, such as the energy focusing degree and the wave focusing position, is thoroughly investigated.
From Loschmidt daemons to time-reversed waves.
Fink, Mathias
2016-06-13
Time-reversal invariance can be exploited in wave physics to control wave propagation in complex media. Because time and space play a similar role in wave propagation, time-reversed waves can be obtained by manipulating spatial boundaries or by manipulating time boundaries. The two dual approaches will be discussed in this paper. The first approach uses 'time-reversal mirrors' with a wave manipulation along a spatial boundary sampled by a finite number of antennas. Related to this method, the role of the spatio-temporal degrees of freedom of the wavefield will be emphasized. In a second approach, waves are manipulated from a time boundary and we show that 'instantaneous time mirrors', mimicking the Loschmidt point of view, simultaneously acting in the entire space at once can also radiate time-reversed waves. © 2016 The Author(s).
Nonlinear acoustic wave equations with fractional loss operators.
Prieur, Fabrice; Holm, Sverre
2011-09-01
Fractional derivatives are well suited to describe wave propagation in complex media. When introduced in classical wave equations, they allow a modeling of attenuation and dispersion that better describes sound propagation in biological tissues. Traditional constitutive equations from solid mechanics and heat conduction are modified using fractional derivatives. They are used to derive a nonlinear wave equation which describes attenuation and dispersion laws that match observations. This wave equation is a generalization of the Westervelt equation, and also leads to a fractional version of the Khokhlov-Zabolotskaya-Kuznetsov and Burgers' equations. © 2011 Acoustical Society of America
Advanced Millimeter-Wave Imaging Enhances Security Screening
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sheen, David M.; Bernacki, Bruce E.; McMakin, Douglas L.
2012-01-12
Millimeter-wave imaging is rapidly gaining acceptance for passenger screening at airports and other secured facilities. This paper details a number of techniques developed over the last several years including novel image reconstruction and display techniques, polarimetric imaging techniques, array switching schemes, as well as high frequency high bandwidth techniques. Implementation of some of these methods will increase the cost and complexity of the mm-wave security portal imaging systems. RF photonic methods may provide new solutions to the design and development of the sequentially switched linear mm-wave arrays that are the key element in the mm-wave portal imaging systems.
Advanced Millimeter-Wave Security Portal Imaging Techniques
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sheen, David M.; Bernacki, Bruce E.; McMakin, Douglas L.
2012-04-01
Millimeter-wave imaging is rapidly gaining acceptance for passenger screening at airports and other secured facilities. This paper details a number of techniques developed over the last several years including novel image reconstruction and display techniques, polarimetric imaging techniques, array switching schemes, as well as high frequency high bandwidth techniques. Implementation of some of these methods will increase the cost and complexity of the mm-wave security portal imaging systems. RF photonic methods may provide new solutions to the design and development of the sequentially switched linear mm-wave arrays that are the key element in the mm-wave portal imaging systems.
Direct manipulation of wave amplitude and phase through inverse design of isotropic media
NASA Astrophysics Data System (ADS)
Liu, Y.; Vial, B.; Horsley, S. A. R.; Philbin, T. G.; Hao, Y.
2017-07-01
In this article we propose a new design methodology allowing us to control both amplitude and phase of electromagnetic waves from a cylindrical incident wave. This results in isotropic materials and does not resort to transformation optics or its quasi-conformal approximations. Our method leads to two-dimensional isotropic, inhomogeneous material profiles of permittivity and permeability, to which a general class of scattering-free wave solutions arise. Our design is based on the separation of the complex wave solution into amplitude and phase. We give two types of examples to validate our methodology.
2011-01-01
Background In Drosophila, the Enhancer of split complex (E(spl)-C) comprises 11 bHLH and Bearded genes that function during Notch signaling to repress proneural identity in the developing peripheral nervous system. Comparison with other insects indicates that the basal state for Diptera is a single bHLH and Bearded homolog and that the expansion of the gene complex occurred in the lineage leading to Drosophila. However, comparative genomic data from other fly species that would elucidate the origin and sequence of gene duplication for the complex is lacking. Therefore, in order to examine the evolutionary history of the complex within Diptera, we reconstructed, using several fosmid clones, the entire E(spl)-complex in the stalk-eyed fly, Teleopsis dalmanni and collected additional homologs of E(spl)-C genes from searches of dipteran EST databases and the Glossina morsitans genome assembly. Results Comparison of the Teleopsis E(spl)-C gene organization with Drosophila indicates complete conservation in gene number and orientation between the species except that T. dalmanni contains a duplicated copy of E(spl)m5 that is not present in Drosophila. Phylogenetic analysis of E(spl)-complex bHLH and Bearded genes for several dipteran species clearly demonstrates that all members of the complex were present prior to the diversification of schizophoran flies. Comparison of upstream regulatory elements and 3' UTR domains between the species also reveals strong conservation for many of the genes and identifies several novel characteristics of E(spl)-C regulatory evolution including the discovery of a previously unidentified, highly conserved SPS+A domain between E(spl)mγ and E(spl)mβ. Conclusion Identifying the phylogenetic origin of E(spl)-C genes and their associated regulatory DNA is essential to understanding the functional significance of this well-studied gene complex. Results from this study provide numerous insights into the evolutionary history of the complex and will help refine the focus of studies examining the adaptive consequences of this gene expansion. PMID:22151427
Chronopoulos, Dimitrios; Collet, Manuel; Ichchou, Mohamed
2015-02-17
The waves propagating within complex smart structures are hereby computed by employing a wave and finite element method. The structures can be of arbitrary layering and of complex geometric characteristics as long as they exhibit two-dimensional periodicity. The piezoelectric coupling phenomena are considered within the finite element formulation. The mass, stiffness and piezoelectric stiffness matrices of the modelled segment can be extracted using a conventional finite element code. The post-processing of these matrices involves the formulation of an eigenproblem whose solutions provide the phase velocities for each wave propagating within the structure and for any chosen direction of propagation. The model is then modified in order to account for a shunted piezoelectric patch connected to the composite structure. The impact of the energy dissipation induced by the shunted circuit on the total damping loss factor of the composite panel is then computed. The influence of the additional mass and stiffness provided by the attached piezoelectric devices on the wave propagation characteristics of the structure is also investigated.
Optical vortex knots – one photon at a time
Tempone-Wiltshire, Sebastien J.; Johnstone, Shaun P.; Helmerson, Kristian
2016-01-01
Feynman described the double slit experiment as “a phenomenon which is impossible, absolutely impossible, to explain in any classical way and which has in it the heart of quantum mechanics”. The double-slit experiment, performed one photon at a time, dramatically demonstrates the particle-wave duality of quantum objects by generating a fringe pattern corresponding to the interference of light (a wave phenomenon) from two slits, even when there is only one photon (a particle) at a time passing through the apparatus. The particle-wave duality of light should also apply to complex three dimensional optical fields formed by multi-path interference, however, this has not been demonstrated. Here we observe particle-wave duality of a three dimensional field by generating a trefoil optical vortex knot – one photon at a time. This result demonstrates a fundamental physical principle, that particle-wave duality implies interference in both space (between spatially distinct modes) and time (through the complex evolution of the superposition of modes), and has implications for topologically entangled single photon states, orbital angular momentum multiplexing and topological quantum computing. PMID:27087642
Chronopoulos, Dimitrios; Collet, Manuel; Ichchou, Mohamed; Shah, Tahir
2015-01-01
The waves propagating within complex smart structures are hereby computed by employing a wave and finite element method. The structures can be of arbitrary layering and of complex geometric characteristics as long as they exhibit two-dimensional periodicity. The piezoelectric coupling phenomena are considered within the finite element formulation. The mass, stiffness and piezoelectric stiffness matrices of the modelled segment can be extracted using a conventional finite element code. The post-processing of these matrices involves the formulation of an eigenproblem whose solutions provide the phase velocities for each wave propagating within the structure and for any chosen direction of propagation. The model is then modified in order to account for a shunted piezoelectric patch connected to the composite structure. The impact of the energy dissipation induced by the shunted circuit on the total damping loss factor of the composite panel is then computed. The influence of the additional mass and stiffness provided by the attached piezoelectric devices on the wave propagation characteristics of the structure is also investigated. PMID:28787972
Carabeo, Rey A; Dooley, Cheryl A; Grieshaber, Scott S; Hackstadt, Ted
2007-09-01
Chlamydiae are Gram-negative obligate intracellular pathogens to which access to an intracellular environment is fundamental to their development. Chlamydial attachment to host cells induces the activation of the Rac GTPase, which is required for the localization of WAVE2 at the sites of chlamydial entry. Co-immunoprecipitation experiments demonstrated that Chlamydia trachomatis infection promoted the interaction of Rac with WAVE2 and Abi-1, but not with IRSp53. siRNA depletion of WAVE2 and Abi-1 abrogated chlamydia-induced actin recruitment and significantly reduced the uptake of the pathogen by the depleted cells. Chlamydia invasion also requires the Arp2/3 complex as demonstrated by its localization to the sites of chlamydial attachment and the reduced efficiency of chlamydial invasion in cells overexpressing the VCA domain of the neural Wiskott-Aldrich syndrome protein. Thus, C. trachomatis activates Rac and promotes its interaction with WAVE2 and Abi-1 to activate the Arp2/3 complex resulting in the induction of actin cytoskeletal rearrangements that are required for invasion.
Modelling and analysis of gene regulatory network using feedback control theory
NASA Astrophysics Data System (ADS)
El-Samad, H.; Khammash, M.
2010-01-01
Molecular pathways are a part of a remarkable hierarchy of regulatory networks that operate at all levels of organisation. These regulatory networks are responsible for much of the biological complexity within the cell. The dynamic character of these pathways and the prevalence of feedback regulation strategies in their operation make them amenable to systematic mathematical analysis using the same tools that have been used with success in analysing and designing engineering control systems. In this article, we aim at establishing this strong connection through various examples where the behaviour exhibited by gene networks is explained in terms of their underlying control strategies. We complement our analysis by a survey of mathematical techniques commonly used to model gene regulatory networks and analyse their dynamic behaviour.
Rogue-wave bullets in a composite (2+1)D nonlinear medium.
Chen, Shihua; Soto-Crespo, Jose M; Baronio, Fabio; Grelu, Philippe; Mihalache, Dumitru
2016-07-11
We show that nonlinear wave packets localized in two dimensions with characteristic rogue wave profiles can propagate in a third dimension with significant stability. This unique behavior makes these waves analogous to light bullets, with the additional feature that they propagate on a finite background. Bulletlike rogue-wave singlet and triplet are derived analytically from a composite (2+1)D nonlinear wave equation. The latter can be interpreted as the combination of two integrable (1+1)D models expressed in different dimensions, namely, the Hirota equation and the complex modified Korteweg-de Vries equation. Numerical simulations confirm that the generation of rogue-wave bullets can be observed in the presence of spontaneous modulation instability activated by quantum noise.
Observation of Wood's anomalies on surface gravity waves propagating on a channel.
Schmessane, Andrea
2016-09-01
I report on experiments demonstrating the appearance of Wood's anomalies in surface gravity waves propagating along a channel with a submerged obstacle. Space-time measurements of surface gravity waves allow one to compute the stationary complex field of the wave and the amplitude growth of localized and propagative modes over all the entire channel, including the scattering region. This allows one to access the near and far field dynamics, which constitute a new and complementary way of observation of mode resonances of the incoming wave displaying Wood's anomalies. Transmission coefficient, dispersion relations and normalized wave energy of the incoming wave and the excited mode are measured and found to be in good agreement with theoretical predictions.
Regulatory logic of pan-neuronal gene expression in C. elegans
Stefanakis, Nikolaos; Carrera, Ines; Hobert, Oliver
2015-01-01
While neuronal cell types display an astounding degree of phenotypic diversity, most if not all neuron types share a core panel of terminal features. However, little is known about how pan-neuronal expression patterns are genetically programmed. Through an extensive analysis of the cis-regulatory control regions of a battery of pan-neuronal C.elegans genes, including genes involved in synaptic vesicle biology and neuropeptide signaling, we define a common organizational principle in the regulation of pan-neuronal genes in the form of a surprisingly complex array of seemingly redundant, parallel-acting cis-regulatory modules that direct expression to broad, overlapping domains throughout the nervous system. These parallel-acting cis-regulatory modules are responsive to a multitude of distinct trans-acting factors. Neuronal gene expression programs therefore fall into two fundamentally distinct classes. Neuron type-specific genes are generally controlled by discrete and non-redundantly acting regulatory inputs, while pan-neuronal gene expression is controlled by diverse, coincident and seemingly redundant regulatory inputs. PMID:26291158
Identification and role of regulatory non-coding RNAs in Listeria monocytogenes.
Izar, Benjamin; Mraheil, Mobarak Abu; Hain, Torsten
2011-01-01
Bacterial regulatory non-coding RNAs control numerous mRNA targets that direct a plethora of biological processes, such as the adaption to environmental changes, growth and virulence. Recently developed high-throughput techniques, such as genomic tiling arrays and RNA-Seq have allowed investigating prokaryotic cis- and trans-acting regulatory RNAs, including sRNAs, asRNAs, untranslated regions (UTR) and riboswitches. As a result, we obtained a more comprehensive view on the complexity and plasticity of the prokaryotic genome biology. Listeria monocytogenes was utilized as a model system for intracellular pathogenic bacteria in several studies, which revealed the presence of about 180 regulatory RNAs in the listerial genome. A regulatory role of non-coding RNAs in survival, virulence and adaptation mechanisms of L. monocytogenes was confirmed in subsequent experiments, thus, providing insight into a multifaceted modulatory function of RNA/mRNA interference. In this review, we discuss the identification of regulatory RNAs by high-throughput techniques and in their functional role in L. monocytogenes.
Characterization of an Explosion Source in a Complex Medium by Modeling and Wavelet Domain Inversion
2006-06-01
1 2. Mechanisms on Scattering due to an Explosive Source...the S wave at the tunnel. TRA has great potential for determining the seismic source properties. 2 2. Mechanisms on Scattering due to an Explosive...and prominent SH and Love waves. Various mechanisms have been proposed to explain the generation of these transverse waves. 2.2 Objectives of This
Pei, Haifeng; Yu, Qiujun; Su, Xiaohua; Wang, Zhen; Zhao, Heng; Yang, Dachun; Yang, Yongjian; Li, De
2016-04-01
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a crucial health problem. With sudden death often being the first presentation, early diagnosis for ARVC is essential. Up to date, electrocardiogram (ECG) is a widely used diagnostic method without invasive harms. To diagnose and treat ARVC as well as possible, we should clearly elucidate its pathophysiological alterations. A 66-year-old farmer presented to the Emergency Department with continuous palpitation, chest tightness, profuse sweating, and nausea with no obvious predisposing causes. An ECG indicated ventricular tachycardia (VT). The patient experienced a sudden drop in blood pressure and acute confusion. After an immediate electrical conversion, his consciousness was gradually restored, and symptoms relieved. The patient was then transferred to the Department of Cardiology to receive ECG, echocardiography, coronary angiogram, biochemical assays, endocardiac tracing, and radiofrequency ablation. In the end, he was diagnosed with ARVC, evidenced by bilateral ventricle dilation and epsilon waves in leads V1-V3. Appropriate therapies were provided for this patient including pharmacological intervention and radiofrequency ablation. Although the diagnosis of ARVC is not difficult, this patient's ECG manifested several interesting features and should be further investigated: T wave inversions were found extensively in the anterior and inferior leads, revealing the involvement of bilateral ventricles; VTs with different morphologies and cycle lengths were found, and some VTs manifested the feature of irregularly irregular rhythm, reminding us to carefully differentiate some special VTs from atrial fibrillation (AF); and epsilon waves gradually appeared in leads V1-V3 and avR since the onset of ARVC. Most importantly, the epsilon waves behind QRS complex appeared in both sinus rhythm and ventricular premature beats/VT originating from cardiac apex, whereas the epsilon waves prior to QRS complex occurred in VT originating from right ventricular outflow tract (RVOT). The features of T wave inversion and epsilon wave in ECGs and the appearance of VTs with different morphologies can reflect the progression of ARVC. The position relationship between epsilon wave and QRS complex in VT depends on ventricular activation sequence, that is, the localization of epsilon wave depends on where VT is originating from.
Experimental investigation on aero-optical aberration of shock wave/boundary layer interactions
NASA Astrophysics Data System (ADS)
Ding, Haolin; Yi, Shihe; Fu, Jia; He, Lin
2016-10-01
After streaming through the flow field which including the expansion, shock wave, boundary, etc., the optical wave would be distorted by fluctuations in the density field. Interactions between laminar/turbulent boundary layer and shock wave contain large number complex flow structures, which offer a condition for studying the influences that different flow structures of the complex flow field have on the aero-optical aberrations. Interactions between laminar/turbulent boundary layer and shock wave are investigated in a Mach 3.0 supersonic wind tunnel, based on nanoparticle-tracer planar laser scattering (NPLS) system. Boundary layer separation/attachment, induced suppression waves, induced shock wave, expansion fan and boundary layer are presented by NPLS images. Its spatial resolution is 44.15 μm/pixel. Time resolution is 6ns. Based on the NPLS images, the density fields with high spatial-temporal resolution are obtained by the flow image calibration, and then the optical path difference (OPD) fluctuations of the original 532nm planar wavefront are calculated using Ray-tracing theory. According to the different flow structures in the flow field, four parts are selected, (1) Y=692 600pixel; (2) Y=600 400pixel; (3) Y=400 268pixel; (4) Y=268 0pixel. The aerooptical effects of different flow structures are quantitatively analyzed, the results indicate that: the compressive waves such as incident shock wave, induced shock wave, etc. rise the density, and then uplift the OPD curve, but this kind of shock are fixed in space position and intensity, the aero-optics induced by it can be regarded as constant; The induced shock waves are induced by the coherent structure of large size vortex in the interaction between turbulent boundary layer, its unsteady characteristic decides the induced waves unsteady characteristic; The space position and intensity of the induced shock wave are fixed in the interaction between turbulent boundary layer; The boundary layer aero-optics are induced by the coherent structure of large size vortex, which result in the fluctuation of OPD.
Fault zone characterization using P- and S-waves
NASA Astrophysics Data System (ADS)
Wawerzinek, Britta; Buness, Hermann; Polom, Ulrich; Tanner, David C.; Thomas, Rüdiger
2014-05-01
Although deep fault zones have high potential for geothermal energy extraction, their real usability depends on complex lithological and tectonic factors. Therefore a detailed fault zone exploration using P- and S-wave reflection seismic data is required. P- and S-wave reflection seismic surveys were carried out along and across the eastern border of the Leinetal Graben in Lower Saxony, Germany, to analyse the structural setting, different reflection characteristics and possible anisotropic effects. In both directions the P-wave reflection seismic measurements show a detailed and complex structure. This structure was developed during several tectonic phases and comprises both steeply- and shallowly-dipping faults. In a profile perpendicular to the graben, a strong P-wave reflector is interpreted as shallowly west-dipping fault that is traceable from the surface down to 500 m depth. It is also detectable along the graben. In contrast, the S-waves show different reflection characteristics: There is no indication of the strong P-wave reflector in the S-wave reflection seismic measurements - neither across nor along the graben. Only diffuse S-wave reflections are observable in this region. Due to the higher resolution of S-waves in the near-surface area it is possible to map structures which cannot be detected in P-wave reflection seismic, e.g the thinning of the uppermost Jurassic layer towards the south. In the next step a petrophysical analysis will be conducted by using seismic FD modelling to a) determine the cause (lithological, structural, or a combination of both) of the different reflection characteristics of P- and S-waves, b) characterize the fault zone, as well as c) analyse the influence of different fault zone properties on the seismic wave field. This work is part of the gebo collaborative research programme which is funded by the 'Niedersächsisches Ministerium für Wissenschaft und Kultur' and Baker Hughes.
Rothschild, Freda; Bishop, Alexis I; Kitchen, Marcus J; Paganin, David M
2014-03-24
The Cornu spiral is, in essence, the image resulting from an Argand-plane map associated with monochromatic complex scalar plane waves diffracting from an infinite edge. Argand-plane maps can be useful in the analysis of more general optical fields. We experimentally study particular features of Argand-plane mappings known as "vorticity singularities" that are associated with mapping continuous single-valued complex scalar speckle fields to the Argand plane. Vorticity singularities possess a hierarchy of Argand-plane catastrophes including the fold, cusp and elliptic umbilic. We also confirm their connection to vortices in two-dimensional complex scalar waves. The study of vorticity singularities may also have implications for higher-dimensional fields such as coherence functions and multi-component fields such as vector and spinor fields.
Magnetic field effects and waves in complex plasmas
NASA Astrophysics Data System (ADS)
Kählert, Hanno; Melzer, André; Puttscher, Marian; Ott, Torben; Bonitz, Michael
2018-05-01
Magnetic fields can modify the physical properties of a complex plasma in various different ways. Weak magnetic fields in the mT range affect only the electrons while strong fields in the Tesla regime also magnetize the ions. In a rotating dusty plasma, the Coriolis force substitutes the Lorentz force and can be used to create an effective magnetization for the strongly coupled dust particles while leaving electrons and ions unaffected. Here, we present a summary of our recent experimental and theoretical work on magnetized complex plasmas. We discuss the dynamics of dust particles in magnetized discharges, the wave spectra of strongly coupled plasmas, and the excitations in confined plasmas. Contribution to the Topical Issue "Fundamentals of Complex Plasmas", edited by Jürgen Meichsner, Michael Bonitz, Holger Fehske, Alexander Piel.
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.
Ay, Ahmet; Holland, Jack; Sperlea, Adriana; Devakanmalai, Gnanapackiam Sheela; Knierer, Stephan; Sangervasi, Sebastian; Stevenson, Angel; Özbudak, Ertuğrul M.
2014-01-01
The vertebrate segmentation clock is a gene expression oscillator controlling rhythmic segmentation of the vertebral column during embryonic development. The period of oscillations becomes longer as cells are displaced along the posterior to anterior axis, which results in traveling waves of clock gene expression sweeping in the unsegmented tissue. Although various hypotheses necessitating the inclusion of additional regulatory genes into the core clock network at different spatial locations have been proposed, the mechanism underlying traveling waves has remained elusive. Here, we combined molecular-level computational modeling and quantitative experimentation to solve this puzzle. Our model predicts the existence of an increasing gradient of gene expression time delays along the posterior to anterior direction to recapitulate spatiotemporal profiles of the traveling segmentation clock waves in different genetic backgrounds in zebrafish. We validated this prediction by measuring an increased time delay of oscillatory Her1 protein production along the unsegmented tissue. Our results refuted the need for spatial expansion of the core feedback loop to explain the occurrence of traveling waves. Spatial regulation of gene expression time delays is a novel way of creating dynamic patterns; this is the first report demonstrating such a control mechanism in any tissue and future investigations will explore the presence of analogous examples in other biological systems. PMID:25336742
Takahashi, Kazuhide; Suzuki, Katsuo
2011-11-01
Cell migration is accomplished by the formation of cellular protrusions such as lamellipodia and filopodia. These protrusions result from actin filament (F-actin) rearrangement at the cell cortex by WASP/WAVE family proteins and Drosophila enabled (Ena)/vasodilator-stimulated factor proteins. However, the role of each of these actin cytoskeletal regulatory proteins in the regulation of three-dimensional cell invasion remains to be clarified. We found that platelet-derived growth factor (PDGF) induces invasion of MDA-MB-231 human breast cancer cells through invasion chamber membrane pores. This invasion was accompanied by intensive F-actin accumulation at the sites of cell infiltration. After PDGF stimulation, WAVE2, N-WASP, and a mammalian Ena (Mena) colocalized with F-actin at the sites of cell infiltration in a phosphatidylinositol 3-kinase (PI3K)-dependent manner. Depletion of WAVE2, N-WASP, or Mena by RNA interference (RNAi) abrogated both cell invasion and intensive F-actin accumulation at the invasion site. These results indicate that by mediating intensive F-actin accumulation at the sites of cell infiltration, WAVE2, N-WASP, and Mena are crucial for PI3K-dependent cell invasion induced by PDGF. Copyright © 2011 Wiley Periodicals, Inc.
Federal Register 2010, 2011, 2012, 2013, 2014
2011-02-01
... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-63777; File No. SR-Phlx-2010-157] Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Approving a Proposed Rule Change, as Modified by Amendment Nos. 1 and 2, Relating to Complex Orders January 26, 2011. I. Introduction On November 29, 2010, NASDAQ OMX PHLX LLC (``Phlx'' or the ``Exchange'...
Novel excipients - Regulatory challenges and perspectives - The EU insight.
Kozarewicz, Piotr; Loftsson, Thorsteinn
2018-05-21
Novel excipients are indispensable in development of modern, advanced drug delivery systems and biotechnology-derived drugs. Although numerous novel excipients are developed for pharmaceutical use, they are not frequently seen in medicinal products due to the strict regulatory requirements and perception that their use makes new product evaluation more complex with risk of delays in the approval process. Regulators regard novel excipients as new substances and whenever new excipient is used in a formulation it must be subjected to full evaluation, similarly to the one required for new active substance. Consequently, the amount of information required in support of the regulatory approval (i.e. marketing authorization) is much more complex and comprehensive than for established excipients. This short review provides an insight into the use of novel excipients in medicinal products approved in the European Union. In addition, barriers and challenges in development of novel excipients are being discussed as well as means to overcome those barriers. Copyright © 2018 Elsevier B.V. All rights reserved.
Architecture of the 99 bp DNA-six-protein regulatory complex of the lambda att site.
Sun, Xingmin; Mierke, Dale F; Biswas, Tapan; Lee, Sang Yeol; Landy, Arthur; Radman-Livaja, Marta
2006-11-17
The highly directional and tightly regulated recombination reaction used to site-specifically excise the bacteriophage lambda chromosome out of its E. coli host chromosome requires the binding of six sequence-specific proteins to a 99 bp segment of the phage att site. To gain structural insights into this recombination pathway, we measured 27 FRET distances between eight points on the 99 bp regulatory DNA bound with all six proteins. Triangulation of these distances using a metric matrix distance-geometry algorithm provided coordinates for these eight points. The resulting path for the protein-bound regulatory DNA, which fits well with the genetics, biochemistry, and X-ray crystal structures describing the individual proteins and their interactions with DNA, provides a new structural perspective into the molecular mechanism and regulation of the recombination reaction and illustrates a design by which different families of higher-order complexes can be assembled from different numbers and combinations of the same few proteins.
Regulatory variation: an emerging vantage point for cancer biology.
Li, Luolan; Lorzadeh, Alireza; Hirst, Martin
2014-01-01
Transcriptional regulation involves complex and interdependent interactions of noncoding and coding regions of the genome with proteins that interact and modify them. Genetic variation/mutation in coding and noncoding regions of the genome can drive aberrant transcription and disease. In spite of accounting for nearly 98% of the genome comparatively little is known about the contribution of noncoding DNA elements to disease. Genome-wide association studies of complex human diseases including cancer have revealed enrichment for variants in the noncoding genome. A striking finding of recent cancer genome re-sequencing efforts has been the previously underappreciated frequency of mutations in epigenetic modifiers across a wide range of cancer types. Taken together these results point to the importance of dysregulation in transcriptional regulatory control in genesis of cancer. Powered by recent technological advancements in functional genomic profiling, exploration of normal and transformed regulatory networks will provide novel insight into the initiation and progression of cancer and open new windows to future prognostic and diagnostic tools. © 2013 Wiley Periodicals, Inc.
The Yeast Nuclear Pore Complex and Transport Through It
Aitchison, John D.; Rout, Michael P.
2012-01-01
Exchange of macromolecules between the nucleus and cytoplasm is a key regulatory event in the expression of a cell’s genome. This exchange requires a dedicated transport system: (1) nuclear pore complexes (NPCs), embedded in the nuclear envelope and composed of proteins termed nucleoporins (or “Nups”), and (2) nuclear transport factors that recognize the cargoes to be transported and ferry them across the NPCs. This transport is regulated at multiple levels, and the NPC itself also plays a key regulatory role in gene expression by influencing nuclear architecture and acting as a point of control for various nuclear processes. Here we summarize how the yeast Saccharomyces has been used extensively as a model system to understand the fundamental and highly conserved features of this transport system, revealing the structure and function of the NPC; the NPC’s role in the regulation of gene expression; and the interactions of transport factors with their cargoes, regulatory factors, and specific nucleoporins. PMID:22419078
BET Bromodomain Inhibition Releases the Mediator Complex from Select cis-Regulatory Elements.
Bhagwat, Anand S; Roe, Jae-Seok; Mok, Beverly Y L; Hohmann, Anja F; Shi, Junwei; Vakoc, Christopher R
2016-04-19
The bromodomain and extraterminal (BET) protein BRD4 can physically interact with the Mediator complex, but the relevance of this association to the therapeutic effects of BET inhibitors in cancer is unclear. Here, we show that BET inhibition causes a rapid release of Mediator from a subset of cis-regulatory elements in the genome of acute myeloid leukemia (AML) cells. These sites of Mediator eviction were highly correlated with transcriptional suppression of neighboring genes, which are enriched for targets of the transcription factor MYB and for functions related to leukemogenesis. A shRNA screen of Mediator in AML cells identified the MED12, MED13, MED23, and MED24 subunits as performing a similar regulatory function to BRD4 in this context, including a shared role in sustaining a block in myeloid maturation. These findings suggest that the interaction between BRD4 and Mediator has functional importance for gene-specific transcriptional activation and for AML maintenance. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Complex Regulatory Networks Governing Production of the Glycopeptide A40926.
Alduina, Rosa; Sosio, Margherita; Donadio, Stefano
2018-04-05
Glycopeptides (GPAs) are an important class of antibiotics, with vancomycin and teicoplanin being used in the last 40 years as drugs of last resort to treat infections caused by Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus . A few new GPAs have since reached the market. One of them is dalbavancin, a derivative of A40926 produced by the actinomycete Nonomuraea sp. ATCC 39727, recently classified as N. gerenzanensis . This review summarizes what we currently know on the multilevel regulatory processes governing production of the glycopeptide A40926 and the different approaches used to increase antibiotic yields. Some nutrients, e.g., valine, l-glutamine and maltodextrin, and some endogenous proteins, e.g., Dbv3, Dbv4 and RpoB R , have a positive role on A40926 biosynthesis, while other factors, e.g., phosphate, ammonium and Dbv23, have a negative effect. Overall, the results available so far point to a complex regulatory network controlling A40926 in the native producing strain.
Investigating the transcriptional control of cardiovascular development
Kathiriya, Irfan S.; Nora, Elphege P.; Bruneau, Benoit G.
2015-01-01
Transcriptional regulation of thousands of genes instructs complex morphogenetic and molecular events for heart development. Cardiac transcription factors (TFs) choreograph gene expression at each stage of differentiation by interacting with co-factors, including chromatin-modifying enzymes, and by binding to a constellation of regulatory DNA elements. Here, we present salient examples relevant to cardiovascular development and heart disease and review techniques that can sharpen our understanding of cardiovascular biology. We discuss the interplay between cardiac TFs, cis-regulatory elements and chromatin as dynamic regulatory networks, to orchestrate sequential deployment of the cardiac gene expression program. PMID:25677518
United States Food and Drug Administration Regulation of Gene and Cell Therapies.
Bailey, Alexander M; Arcidiacono, Judith; Benton, Kimberly A; Taraporewala, Zenobia; Winitsky, Steve
2015-01-01
The United States (US) Food and Drug Administration (FDA) is a regulatory agency that has oversight for a wide range of products entering the US market, including gene and cell therapies. The regulatory approach for these products is similar to other medical products within the United States and consists of a multitiered framework of statutes, regulations, and guidance documents. Within this framework, there is considerable flexibility which is necessary due to the biological and technical complexity of these products in general. This chapter provides an overview of the US FDA regulatory oversight of gene and cell therapy products.
Dufour, Yann S.; Donohue, Timothy J.
2015-01-01
Transcriptional regulation plays a significant role in the biological response of bacteria to changing environmental conditions. Therefore, mapping transcriptional regulatory networks is an important step not only in understanding how bacteria sense and interpret their environment but also to identify the functions involved in biological responses to specific conditions. Recent experimental and computational developments have facilitated the characterization of regulatory networks on a genome-wide scale in model organisms. In addition, the multiplication of complete genome sequences has encouraged comparative analyses to detect conserved regulatory elements and infer regulatory networks in other less well-studied organisms. However, transcription regulation appears to evolve rapidly, thus, creating challenges for the transfer of knowledge to nonmodel organisms. Nevertheless, the mechanisms and constraints driving the evolution of regulatory networks have been the subjects of numerous analyses, and several models have been proposed. Overall, the contributions of mutations, recombination, and horizontal gene transfer are complex. Finally, the rapid evolution of regulatory networks plays a significant role in the remarkable capacity of bacteria to adapt to new or changing environments. Conversely, the characteristics of environmental niches determine the selective pressures and can shape the structure of regulatory network accordingly. PMID:23046950
Kang, Jin-Ho; Campos, Marcelo L; Zemelis-Durfee, Starla; Al-Haddad, Jameel M; Jones, A Daniel; Telewski, Frank W; Brandizzi, Federica; Howe, Gregg A
2016-10-01
Trichomes are epidermal structures that provide a first line of defense against arthropod herbivores. The recessive hairless (hl) mutation in tomato (Solanum lycopersicum L.) causes severe distortion of trichomes on all aerial tissues, impairs the accumulation of sesquiterpene and polyphenolic compounds in glandular trichomes, and compromises resistance to the specialist herbivore Manduca sexta Here, we demonstrate that the tomato Hl gene encodes a subunit (SRA1) of the highly conserved WAVE regulatory complex that controls nucleation of actin filaments in a wide range of eukaryotic cells. The tomato SRA1 gene spans a 42-kb region containing both Solyc11g013280 and Solyc11g013290 The hl mutation corresponds to a complex 3-kb deletion that removes the last exon of the gene. Expression of a wild-type SRA1 cDNA in the hl mutant background restored normal trichome development, accumulation of glandular trichome-derived metabolites, and resistance to insect herbivory. These findings establish a role for SRA1 in the development of tomato trichomes and also implicate the actin-cytoskeleton network in cytosolic control of specialized metabolism for plant defense. We also show that the brittleness of hl mutant stems is associated with altered mechanical and cell morphological properties of stem tissue, and demonstrate that this defect is directly linked to the mutation in SRA1. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nottale, Laurent; Célérier, Marie-Noëlle
One of the main results of scale relativity as regards the foundation of quantum mechanics is its explanation of the origin of the complex nature of the wave function. The scale relativity theory introduces an explicit dependence of physical quantities on scale variables, founding itself on the theorem according to which a continuous and non-differentiable space-time is fractal (i.e., scale-divergent). In the present paper, the nature of the scale variables and their relations to resolutions and differential elements are specified in the non-relativistic case (fractal space). We show that, owing to the scale-dependence which it induces, non-differentiability involves a fundamentalmore » two-valuedness of the mean derivatives. Since, in the scale relativity framework, the wave function is a manifestation of the velocity field of fractal space-time geodesics, the two-valuedness of velocities leads to write them in terms of complex numbers, and yields therefore the complex nature of the wave function, from which the usual expression of the Schrödinger equation can be derived.« less
Huygens' optical vector wave field synthesis via in-plane electric dipole metasurface.
Park, Hyeonsoo; Yun, Hansik; Choi, Chulsoo; Hong, Jongwoo; Kim, Hwi; Lee, Byoungho
2018-04-16
We investigate Huygens' optical vector wave field synthesis scheme for electric dipole metasurfaces with the capability of modulating in-plane polarization and complex amplitude and discuss the practical issues involved in realizing multi-modulation metasurfaces. The proposed Huygens' vector wave field synthesis scheme identifies the vector Airy disk as a synthetic unit element and creates a designed vector optical field by integrating polarization-controlled and complex-modulated Airy disks. The metasurface structure for the proposed vector field synthesis is analyzed in terms of the signal-to-noise ratio of the synthesized field distribution. The design of practical metasurface structures with true vector modulation capability is possible through the analysis of the light field modulation characteristics of various complex modulated geometric phase metasurfaces. It is shown that the regularization of meta-atoms is a key factor that needs to be considered in field synthesis, given that it is essential for a wide range of optical field synthetic applications, including holographic displays, microscopy, and optical lithography.
Topography Estimation of the Core Mantle Boundary with ScS Reverberations and Diffraction Waves
NASA Astrophysics Data System (ADS)
Hein, B. E.; Nakata, N.
2017-12-01
In this study, we use the propagation of global seismic waves to study the Core Mantle Boundary (CMB). We focus on the use of S-wave reflections at the CMB (ScS reverberations) and outer-core diffracted waves. It is difficult imaging the CMB with the ScS wave because the complexity of the structure in the near surface ( 50 km); the complex structure degrades the signal-to-noise ratio of of the ScS. To avoid estimating the structure in the crust, we rely on the concept of seismic interferometry to extract wave propagation through mantle, but not through the crust. Our approach is compute the deconvolution between the ScS (and its reverberation) and direct S waves generated by intermediate to deep earthquakes (>50 km depth). Through this deconvolution, we have the ability to filter out the direct S wave and retrieve the wave field propagating from only the hypocenter to the outer core, but not between the hypocenter to the receiver. After the deconvolution, we can isolate the CMB reflected waves from the complicated wave phenomena because of the near-surface structure. Utilizing intermediate and deep earthquakes is key since we can suppress the near-surface effect from the surface to the hypocenter of the earthquakes. The variation of such waves (e.g., travel-time perturbation and/or wavefield decorrelation) at different receivers and earthquakes provides the information of the topography of the CMB. In order to get a more detailed image of the topography of the CMB we use diffracted seismic waves such as Pdiff , Sdiff, and P'P'. By using two intermediate to deep earthquakes on a great circle path with a station we can extract the wave propagation between the two earthquakes to simplify the waveform, similar to how it is preformed using the ScS wave. We generate more illumination of the CMB by using diffracted waves rather than only using ScS reverberations. The accurate topography of CMB obtained by these deconvolution analyses may provide new insight of the dynamics of the Earth such as heat flow at the CMB and through the mantle.
Adult family relationships in the context of friendship
Fuller-Iglesias, Heather R.; Webster, Noah; Antonucci, Toni C.
2013-01-01
The present study examined the complex way in which relationships with family and friends shape health and well-being in adulthood over time. Specifically, we explored whether the longitudinal effects of positive and negative family relationship quality on health and well-being differ in the context of varying levels of positive friend relationships. Data were from two waves (1992/1993 and 2005) of the Social Relations, Aging and Health Study. The sample included respondents aged 18 and older at Wave 1 who reported having a best friend at both waves (N = 455), and consisted of 291 (64%) women and 164 (36%) men. Wave 1 friend positivity and family positivity interacted to predict self-rated health but not self-esteem, indicating that among respondents with a less positive friend relationship, more positive family relationships were related to worse health at Wave 2. Wave 1 friend positivity and family negativity significantly interacted to predict self-rated health and self-esteem at Wave 2. The nature of the interactions were consistent in that among respondents with a more highly positive friend relationship, less negative family relationships were linked to better health and self-esteem at Wave 2. Findings provide insight into the complex way in which social relations impact positive outcomes in adulthood. Previous studies have documented the consistent and straightforward manner in which negative relationships impact health and well-being, whereas this study illustrates that the role of positive social relations is more variable and dependent on multiple relationship contexts. PMID:24273462