Regulation of cytoskeletal organization by syndecan transmembrane proteoglycans

DEFF Research Database (Denmark)

Yoneda, Atsuko; Couchman, John R

2003-01-01

have recently suggested that signaling through core protein of syndecans can regulate cytoskeletal organization through their clustering, association with cytoskeletal structures, binding to cytoplasmic binding proteins, and intracellular phosphorylation. Here we will review current understanding...... of signaling through syndecans in cytoskeletal organization....

Neoplastic progression of the human breast cancer cell line G3S1 is associated with elevation of cytoskeletal dynamics and upregulation of MT1-MMP

Czech Academy of Sciences Publication Activity Database

Tolde, O.; Rosel, D.; Mierke, C.T.; Paňková, D.; Folk, P.; Veselý, Pavel; Brabek, J.

2010-01-01

Roč. 36, č. 4 (2010), s. 833-839 ISSN 1019-6439 R&D Projects: GA MŠk(CZ) LC06061 Institutional research plan: CEZ:AV0Z50520514 Keywords : invasiveness * neoplastic progression * cytoskeletal dynamics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.571, year: 2010

Modulators of cytoskeletal reorganization in CA1 hippocampal neurons show increased expression in patients at mid-stage Alzheimer's disease.

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Patricia F Kao

2010-10-01

Full Text Available During the progression of Alzheimer's disease (AD, hippocampal neurons undergo cytoskeletal reorganization, resulting in degenerative as well as regenerative changes. As neurofibrillary tangles form and dystrophic neurites appear, sprouting neuronal processes with growth cones emerge. Actin and tubulin are indispensable for normal neurite development and regenerative responses to injury and neurodegenerative stimuli. We have previously shown that actin capping protein beta2 subunit, Capzb2, binds tubulin and, in the presence of tau, affects microtubule polymerization necessary for neurite outgrowth and normal growth cone morphology. Accordingly, Capzb2 silencing in hippocampal neurons resulted in short, dystrophic neurites, seen in neurodegenerative diseases including AD. Here we demonstrate the statistically significant increase in the Capzb2 expression in the postmortem hippocampi in persons at mid-stage, Braak and Braak stage (BB III-IV, non-familial AD in comparison to controls. The dynamics of Capzb2 expression in progressive AD stages cannot be attributed to reactive astrocytosis. Moreover, the increased expression of Capzb2 mRNA in CA1 pyramidal neurons in AD BB III-IV is accompanied by an increased mRNA expression of brain derived neurotrophic factor (BDNF receptor tyrosine kinase B (TrkB, mediator of synaptic plasticity in hippocampal neurons. Thus, the up-regulation of Capzb2 and TrkB may reflect cytoskeletal reorganization and/or regenerative response occurring in hippocampal CA1 neurons at a specific stage of AD progression.

Fragility of foot process morphology in kidney podocytes arises from chaotic spatial propagation of cytoskeletal instability.

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Cibele V Falkenberg

2017-03-01

Full Text Available Kidney podocytes' function depends on fingerlike projections (foot processes that interdigitate with those from neighboring cells to form the glomerular filtration barrier. The integrity of the barrier depends on spatial control of dynamics of actin cytoskeleton in the foot processes. We determined how imbalances in regulation of actin cytoskeletal dynamics could result in pathological morphology. We obtained 3-D electron microscopy images of podocytes and used quantitative features to build dynamical models to investigate how regulation of actin dynamics within foot processes controls local morphology. We find that imbalances in regulation of actin bundling lead to chaotic spatial patterns that could impair the foot process morphology. Simulation results are consistent with experimental observations for cytoskeletal reconfiguration through dysregulated RhoA or Rac1, and they predict compensatory mechanisms for biochemical stability. We conclude that podocyte morphology, optimized for filtration, is intrinsically fragile, whereby local transient biochemical imbalances may lead to permanent morphological changes associated with pathophysiology.

Cytoskeletal defects in Bmpr2-associated pulmonary arterial hypertension.

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Johnson, Jennifer A; Hemnes, Anna R; Perrien, Daniel S; Schuster, Manfred; Robinson, Linda J; Gladson, Santhi; Loibner, Hans; Bai, Susan; Blackwell, Tom R; Tada, Yuji; Harral, Julie W; Talati, Megha; Lane, Kirk B; Fagan, Karen A; West, James

2012-03-01

The heritable form of pulmonary arterial hypertension (PAH) is typically caused by a mutation in bone morphogenic protein receptor type 2 (BMPR2), and mice expressing Bmpr2 mutations develop PAH with features similar to human disease. BMPR2 is known to interact with the cytoskeleton, and human array studies in PAH patients confirm alterations in cytoskeletal pathways. The goal of this study was to evaluate cytoskeletal defects in BMPR2-associated PAH. Expression arrays on our Bmpr2 mutant mouse lungs revealed cytoskeletal defects as a prominent molecular consequence of universal expression of a Bmpr2 mutation (Rosa26-Bmpr2(R899X)). Pulmonary microvascular endothelial cells cultured from these mice have histological and functional cytoskeletal defects. Stable transfection of different BMPR2 mutations into pulmonary microvascular endothelial cells revealed that cytoskeletal defects are common to multiple BMPR2 mutations and are associated with activation of the Rho GTPase, Rac1. Rac1 defects are corrected in cell culture and in vivo through administration of exogenous recombinant human angiotensin-converting enzyme 2 (rhACE2). rhACE2 reverses 77% of gene expression changes in Rosa26-Bmpr2(R899X) transgenic mice, in particular, correcting defects in cytoskeletal function. Administration of rhACE2 to Rosa26-Bmpr2(R899X) mice with established PAH normalizes pulmonary pressures. Together, these findings suggest that cytoskeletal function is central to the development of BMPR2-associated PAH and that intervention against cytoskeletal defects may reverse established disease.

Aggregatibacter actinomycetemcomitans lipopolysaccharide affects human gingival fibroblast cytoskeletal organization.

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Gutiérrez-Venegas, Gloria; Contreras-Marmolejo, Luis Arturo; Román-Alvárez, Patricia; Barajas-Torres, Carolina

2008-04-01

The cytoskeleton is a dynamic structure that plays a key role in maintaining cell morphology and function. This study investigates the effect of bacterial wall lipopolysaccharide (LPS), a strong inflammatory agent, on the dynamics and organization of actin, tubulin, vimentin, and vinculin proteins in human gingival fibroblasts (HGF). A time-dependent study showed a noticeable change in actin architecture after 1.5 h of incubation with LPS (1 microg/ml) with the formation of orthogonal fibers and further accumulation of actin filament at the cell periphery by 24 h. When 0.01-10 microg/ml of LPS was added to human gingival fibroblast cultures, cells acquired a round, flat shape and gradually developed cytoplasmic ruffling. Lipopolysaccharides extracted from Aggregatibacter actinomycetemcomitans periodontopathogenic bacteria promoted alterations in F-actin stress fibres of human gingival cells. Normally, human gingival cells have F-actin fibres that are organized in linear distribution throughout the cells, extending along the cell's length. LPS-treated cells exhibited changes in cytoskeletal protein organization, and F-actin was reorganized by the formation of bundles underneath and parallel to the cell membrane. We also found the reorganization of the vimentin network into vimentin bundling after 1.5 h of treatment. HGF cells exhibited diffuse and granular gamma-tubulin stain. There was no change in LPS-treated HGF. However, vinculin plaques distributed in the cell body diminished after LPS treatment. We conclude that the dynamic and structured organization of cytoskeletal filaments and actin assembly in human gingival fibroblasts is altered by LPS treatment and is accompanied by a decrease in F-actin pools.

Kynurenic Acid Prevents Cytoskeletal Disorganization Induced by Quinolinic Acid in Mixed Cultures of Rat Striatum.

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Pierozan, Paula; Biasibetti-Brendler, Helena; Schmitz, Felipe; Ferreira, Fernanda; Pessoa-Pureur, Regina; Wyse, Angela T S

2018-06-01

Kynurenic acid (KYNA) is a neuroactive metabolite of tryptophan known to modulate a number of mechanisms involved in neural dysfunction. Although its activity in the brain has been widely studied, the effect of KYNA counteracting the actions of quinolinic acid (QUIN) remains unknown. The present study aims at describing the ability of 100 μM KYNA preventing cytoskeletal disruption provoked by QUIN in astrocyte/neuron/microglia mixed culture. KYNA totally preserved cytoskeletal organization, cell morphology, and redox imbalance in mixed cultures exposed to QUIN. However, KYNA partially prevented morphological alteration in isolated primary astrocytes and failed to protect the morphological alterations of neurons caused by QUIN exposure. Moreover, KYNA prevented QUIN-induced microglial activation and upregulation of ionized calcium-binding adapter molecule 1 (Iba-1) and partially preserved tumor necrosis factor-α (TNF-α) level in mixed cultures. TNF-α level was also partially preserved in astrocytes. In addition to the mechanisms dependent on redox imbalance and microglial activation, KYNA prevented downregulation of connexin-43 and the loss of functionality of gap junctions (GJs), preserving cell-cell contact, cytoskeletal organization, and cell morphology in QUIN-treated cells. Furthermore, the toxicity of QUIN targeting the cytoskeleton of mixed cultures was not prevented by the N-methyl-D-aspartate (NMDA) antagonist MK-801. We suggest that KYNA protects the integrity of the cytoskeleton of mixed cultures by complex mechanisms including modulating microglial activation preventing oxidative imbalance and misregulated GJs leading to disrupted cytoskeleton in QUIN-treated cells. This study contributed to elucidate the molecular basis of KYNA protection against QUIN toxicity.

Topography on a subcellular scale modulates cellular adhesions and actin stress fiber dynamics in tumor associated fibroblasts

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Azatov, Mikheil; Sun, Xiaoyu; Suberi, Alexandra; Fourkas, John T.; Upadhyaya, Arpita

2017-12-01

Cells can sense and adapt to mechanical properties of their environment. The local geometry of the extracellular matrix, such as its topography, has been shown to modulate cell morphology, migration, and proliferation. Here we investigate the effect of micro/nanotopography on the morphology and cytoskeletal dynamics of human pancreatic tumor-associated fibroblast cells (TAFs). We use arrays of parallel nanoridges with variable spacings on a subcellular scale to investigate the response of TAFs to the topography of their environment. We find that cell shape and stress fiber organization both align along the direction of the nanoridges. Our analysis reveals a strong bimodal relationship between the degree of alignment and the spacing of the nanoridges. Furthermore, focal adhesions align along ridges and form preferentially on top of the ridges. Tracking actin stress fiber movement reveals enhanced dynamics of stress fibers on topographically patterned surfaces. We find that components of the actin cytoskeleton move preferentially along the ridges with a significantly higher velocity along the ridges than on a flat surface. Our results suggest that a complex interplay between the actin cytoskeleton and focal adhesions coordinates the cellular response to micro/nanotopography.

Arabidopsis FH1 Formin Affects Cotyledon Pavement Cell Shape by Modulating Cytoskeleton Dynamics.

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Rosero, Amparo; Oulehlová, Denisa; Stillerová, Lenka; Schiebertová, Petra; Grunt, Michal; Žárský, Viktor; Cvrčková, Fatima

2016-03-01

Plant cell morphogenesis involves concerted rearrangements of microtubules and actin microfilaments. We previously reported that FH1, the main Arabidopsis thaliana housekeeping Class I membrane-anchored formin, contributes to actin dynamics and microtubule stability in rhizodermis cells. Here we examine the effects of mutations affecting FH1 (At3g25500) on cell morphogenesis and above-ground organ development in seedlings, as well as on cytoskeletal organization and dynamics, using a combination of confocal and variable angle epifluorescence microscopy with a pharmacological approach. Homozygous fh1 mutants exhibited cotyledon epinasty and had larger cotyledon pavement cells with more pronounced lobes than the wild type. The pavement cell shape alterations were enhanced by expression of the fluorescent microtubule marker GFP-microtubule-associated protein 4 (MAP4). Mutant cotyledon pavement cells exhibited reduced density and increased stability of microfilament bundles, as well as enhanced dynamics of microtubules. Analogous results were also obtained upon treatments with the formin inhibitor SMIFH2 (small molecule inhibitor of formin homology 2 domains). Pavement cell shape in wild-type (wt) and fh1 plants in some situations exhibited a differential response towards anti-cytoskeletal drugs, especially the microtubule disruptor oryzalin. Our observations indicate that FH1 participates in the control of microtubule dynamics, possibly via its effects on actin, subsequently influencing cell morphogenesis and macroscopic organ development. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Vitreous-induced cytoskeletal rearrangements via the Rac1 GTPase-dependent signaling pathway in human retinal pigment epithelial cells

International Nuclear Information System (INIS)

Huang, Xionggao; Wei, Yantao; Ma, Haizhi; Zhang, Shaochong

2012-01-01

Highlights: ► Vitreous induces morphological changes and cytoskeletal rearrangements in RPE cells. ► Rac1 is activated in vitreous-transformed RPE cells. ► Rac inhibition prevents morphological changes in vitreous-transformed RPE cells. ► Rac inhibition suppresses cytoskeletal rearrangements in vitreous-transformed RPE cells. ► The vitreous-induced effects are mediated by a Rac1 GTPase/LIMK1/cofilin pathway. -- Abstract: Proliferative vitreoretinopathy (PVR) is mainly caused by retinal pigment epithelial (RPE) cell migration, invasion, proliferation and transformation into fibroblast-like cells that produce the extracellular matrix (ECM). The vitreous humor is known to play an important role in PVR. An epithelial-to-mesenchymal transdifferentiation (EMT) of human RPE cells induced by 25% vitreous treatment has been linked to stimulation of the mesenchymal phenotype, migration and invasion. Here, we characterized the effects of the vitreous on the cell morphology and cytoskeleton in human RPE cells. The signaling pathway that mediates these effects was investigated. Serum-starved RPE cells were incubated with 25% vitreous, and the morphological changes were examined by phase-contrast microscopy. Filamentous actin (F-actin) was examined by immunofluorescence and confocal microscopy. Protein phosphorylation of AKT, ERK1/2, Smad2/3, LIM kinase (LIMK) 1 and cofilin was analyzed by Western blot analysis. Vitreous treatment induced cytoskeletal rearrangements, activated Rac1 and enhanced the phosphorylation of AKT, ERK1/2 and Smad2/3. When the cells were treated with a Rac activation-specific inhibitor, the cytoskeletal rearrangements were prevented, and the phosphorylation of Smad2/3 was blocked. Vitreous treatment also enhanced the phosphorylation of LIMK1 and cofilin and the Rac inhibitor blocked this effect. We propose that vitreous-transformed human RPE cells undergo cytoskeletal rearrangements via Rac1 GTPase-dependent pathways that modulate LIMK1 and

Vitreous-induced cytoskeletal rearrangements via the Rac1 GTPase-dependent signaling pathway in human retinal pigment epithelial cells

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Huang, Xionggao [State Key Ophthalmic Laboratory, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou (China); Department of Ophthalmology, Hainan Medical College, Haikou (China); Wei, Yantao; Ma, Haizhi [State Key Ophthalmic Laboratory, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou (China); Zhang, Shaochong, E-mail: zhshaochong@163.com [State Key Ophthalmic Laboratory, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou (China)

2012-03-09

-transformed human RPE cells undergo cytoskeletal rearrangements via Rac1 GTPase-dependent pathways that modulate LIMK1 and cofilin activity. The TGF{beta}-like activity of the vitreous may participate in this effect. Actin polymerization causes the cytoskeletal rearrangements that lead to the plasticity of vitreous-transformed RPE cells in PVR.

The Emerging Role of the Cytoskeleton in Chromosome Dynamics

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Maya Spichal

2017-05-01

Full Text Available Chromosomes underlie a dynamic organization that fulfills functional roles in processes like transcription, DNA repair, nuclear envelope stability, and cell division. Chromosome dynamics depend on chromosome structure and cannot freely diffuse. Furthermore, chromosomes interact closely with their surrounding nuclear environment, which further constrains chromosome dynamics. Recently, several studies enlighten that cytoskeletal proteins regulate dynamic chromosome organization. Cytoskeletal polymers that include actin filaments, microtubules and intermediate filaments can connect to the nuclear envelope via Linker of the Nucleoskeleton and Cytoskeleton (LINC complexes and transfer forces onto chromosomes inside the nucleus. Monomers of these cytoplasmic polymers and related proteins can also enter the nucleus and play different roles in the interior of the nucleus than they do in the cytoplasm. Nuclear cytoskeletal proteins can act as chromatin remodelers alone or in complexes with other nuclear proteins. They can also act as transcription factors. Many of these mechanisms have been conserved during evolution, indicating that the cytoskeletal regulation of chromosome dynamics is an essential process. In this review, we discuss the different influences of cytoskeletal proteins on chromosome dynamics by focusing on the well-studied model organism budding yeast.

p21-Activated kinase (PAK regulates cytoskeletal reorganization and directional migration in human neutrophils.

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Asako Itakura

Full Text Available Neutrophils serve as a first line of defense in innate immunity owing in part to their ability to rapidly migrate towards chemotactic factors derived from invading pathogens. As a migratory function, neutrophil chemotaxis is regulated by the Rho family of small GTPases. However, the mechanisms by which Rho GTPases orchestrate cytoskeletal dynamics in migrating neutrophils remain ill-defined. In this study, we characterized the role of p21-activated kinase (PAK downstream of Rho GTPases in cytoskeletal remodeling and chemotactic processes of human neutrophils. We found that PAK activation occurred upon stimulation of neutrophils with f-Met-Leu-Phe (fMLP, and PAK accumulated at the actin-rich leading edge of stimulated neutrophils, suggesting a role for PAK in Rac-dependent actin remodeling. Treatment with the pharmacological PAK inhibitor, PF3758309, abrogated the integrity of RhoA-mediated actomyosin contractility and surface adhesion. Moreover, inhibition of PAK activity impaired neutrophil morphological polarization and directional migration under a gradient of fMLP, and was associated with dysregulated Ca(2+ signaling. These results suggest that PAK serves as an important effector of Rho-family GTPases in neutrophil cytoskeletal reorganization, and plays a key role in driving efficient directional migration of human neutrophils.

The integrin alphav beta3 increases cellular stiffness and cytoskeletal remodeling dynamics to facilitate cancer cell invasion

Science.gov (United States)

Mierke, Claudia Tanja

2013-01-01

The process of cancer cell invasion through the extracellular matrix (ECM) of connective tissue plays a prominent role in tumor progression and is based fundamentally on biomechanics. Cancer cell invasion usually requires cell adhesion to the ECM through the cell-matrix adhesion receptors integrins. The expression of the αvβ3 integrin is increased in several tumor types and is consistently associated with increased metastasis formation in patients. The hypothesis was that the αvβ3 integrin expression increases the invasiveness of cancer cells through increased cellular stiffness, and increased cytoskeletal remodeling dynamics. Here, the invasion of cancer cells with different αvβ3 integrin expression levels into dense three-dimensional (3D) ECMs has been studied. Using a cell sorter, two subcell lines expressing either high or low amounts of αvβ3 integrins (αvβ3high or αvβ3low cells, respectively) have been isolated from parental MDA-MB-231 breast cancer cells. αvβ3high cells showed a threefold increased cell invasion compared to αvβ3low cells. Similar results were obtained for A375 melanoma, 786-O kidney and T24 bladder carcinoma cells, and cells in which the β3 integrin subunit was knocked down using specific siRNA. To investigate whether contractile forces are essential for αvβ3 integrin-mediated increased cellular stiffness and subsequently enhanced cancer cell invasion, invasion assays were performed in the presence of myosin light chain kinase inhibitor ML-7 and Rho kinase inhibitor Y27632. Indeed, cancer cell invasiveness was reduced after addition of ML-7 and Y27632 in αvβ3high cells but not in αvβ3low cells. Moreover, after addition of the contractility enhancer calyculin A, an increase in pre-stress in αvβ3low cells was observed, which enhanced cellular invasiveness. In addition, inhibition of the Src kinase, STAT3 or Rac1 strongly reduced the invasiveness of αvβ3high cells, whereas the invasiveness of β3 specific knock

The integrin alphav beta3 increases cellular stiffness and cytoskeletal remodeling dynamics to facilitate cancer cell invasion

International Nuclear Information System (INIS)

Mierke, Claudia Tanja

2013-01-01

The process of cancer cell invasion through the extracellular matrix (ECM) of connective tissue plays a prominent role in tumor progression and is based fundamentally on biomechanics. Cancer cell invasion usually requires cell adhesion to the ECM through the cell-matrix adhesion receptors integrins. The expression of the αvβ3 integrin is increased in several tumor types and is consistently associated with increased metastasis formation in patients. The hypothesis was that the αvβ3 integrin expression increases the invasiveness of cancer cells through increased cellular stiffness, and increased cytoskeletal remodeling dynamics. Here, the invasion of cancer cells with different αvβ3 integrin expression levels into dense three-dimensional (3D) ECMs has been studied. Using a cell sorter, two subcell lines expressing either high or low amounts of αvβ3 integrins (αvβ3 high or αvβ3 low cells, respectively) have been isolated from parental MDA-MB-231 breast cancer cells. αvβ3 high cells showed a threefold increased cell invasion compared to αvβ3 low cells. Similar results were obtained for A375 melanoma, 786-O kidney and T24 bladder carcinoma cells, and cells in which the β3 integrin subunit was knocked down using specific siRNA. To investigate whether contractile forces are essential for αvβ3 integrin-mediated increased cellular stiffness and subsequently enhanced cancer cell invasion, invasion assays were performed in the presence of myosin light chain kinase inhibitor ML-7 and Rho kinase inhibitor Y27632. Indeed, cancer cell invasiveness was reduced after addition of ML-7 and Y27632 in αvβ3 high cells but not in αvβ3 low cells. Moreover, after addition of the contractility enhancer calyculin A, an increase in pre-stress in αvβ3 low cells was observed, which enhanced cellular invasiveness. In addition, inhibition of the Src kinase, STAT3 or Rac1 strongly reduced the invasiveness of αvβ3 high cells, whereas the invasiveness of β3 specific knock

Precortical phase of Alzheimer’s disease (AD)-related tau cytoskeletal pathology

Science.gov (United States)

Stratmann, Katharina; Heinsen, Helmut; Korf, Horst-Werner; Del Turco, Domenico; Ghebremedhin, Estifanos; Seidel, Kay; Bouzrou, Mohamed; Grinberg, Lea T.; Bohl, Jürgen; Wharton, Stephen B; den Dunnen, Wilfred; Rüb, Udo

2015-01-01

Alzheimer’s disease (AD) represents the most frequent progressive neuropsychiatric disorder worldwide leading to dementia and accounts for 60 to 70% of demented individuals. In view of the early appearance of neuronal deposits of the hyperphosphorylated cytoskeletal protein tau in the transentorhinal and entorhinal regions of the allocortex (i.e. in Braak and Braak AD stage I in the evolution of the AD-related cortical tau cytoskeletal pathology) it has been believed for a long time that these allocortical regions represent the first brain targets of the AD-related tau cytoskeletal pathology. However, recent pathoanatomical studies suggested that the subcortical brain nuclei that send efferent projections to the transentorhinal and entorhinal regions may also comprise AD-related cytoskeletal changes already at very early Braak and Braak AD stages. In order to corroborate these initial results we systematically investigated the presence and extent of the AD-related cytoskeletal pathology in serial thick tissue sections through all the subcortical nuclei known to send efferent projections to these vulnerable allocortical regions of three individuals with Braak and Braak AD stage 0 and fourteen individuals with Braak and Braak AD stage I by means of immunostainings with the anti-tau antibody AT8. These investigations revealed consistent AT8 immunoreactive neuronal tau cytoskeletal pathology in a subset of these subcortical nuclei (i.e. medial septal nucleus, nuclei of the vertical and horizontal limbs of the diagonal band of Broca, basal nucleus of Meynert; claustrum; hypothalamic ventromedial, tuberomamillary and supramamillary nuclei, perifornical region and lateral area; thalamic central medial, laterodorsal, subparafascicular, and central lateral nuclei, medial pulvinar and limitans-suprageniculate complex; peripeduncular nucleus, dopaminergic substantia nigra and ventral tegmental area, periaqueductal gray, midbrain and pontine dorsal raphe nuclei, locus

Assembly of the MreB-associated cytoskeletal ring of Escherichia coli.

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Vats, Purva; Shih, Yu-Ling; Rothfield, Lawrence

2009-04-01

The Escherichia coli actin homologue MreB is part of a helical cytoskeletal structure that winds around the cell between the two poles. It has been shown that MreB redistributes during the cell cycle to form circumferential ring structures that flank the cytokinetic FtsZ ring and appear to be associated with division and segregation of the helical cytoskeleton. We show here that the MreB cytoskeletal ring also contains the MreC, MreD, Pbp2 and RodA proteins. Assembly of MreB, MreC, MreD and Pbp2 into the ring structure required the FtsZ ring but no other known components of the cell division machinery, whereas assembly of RodA into the cytoskeletal ring required one or more additional septasomal components. Strikingly, MreB, MreC, MreD and RodA were each able to independently assemble into the cytoskeletal ring and coiled cytoskeletal structures in the absence of any of the other ring components. This excludes the possibility that one or more of these proteins acts as a scaffold for incorporation of the other proteins into these structures. In contrast, incorporation of Pbp2 required the presence of MreC, which may provide a docking site for Pbp2 entry.

Identify Dynamic Network Modules with Temporal and Spatial Constraints

Energy Technology Data Exchange (ETDEWEB)

Jin, R; McCallen, S; Liu, C; Almaas, E; Zhou, X J

2007-09-24

Despite the rapid accumulation of systems-level biological data, understanding the dynamic nature of cellular activity remains a difficult task. The reason is that most biological data are static, or only correspond to snapshots of cellular activity. In this study, we explicitly attempt to detangle the temporal complexity of biological networks by using compilations of time-series gene expression profiling data.We define a dynamic network module to be a set of proteins satisfying two conditions: (1) they form a connected component in the protein-protein interaction (PPI) network; and (2) their expression profiles form certain structures in the temporal domain. We develop the first efficient mining algorithm to discover dynamic modules in a temporal network, as well as frequently occurring dynamic modules across many temporal networks. Using yeast as a model system, we demonstrate that the majority of the identified dynamic modules are functionally homogeneous. Additionally, many of them provide insight into the sequential ordering of molecular events in cellular systems. We further demonstrate that identifying frequent dynamic network modules can significantly increase the signal to noise separation, despite the fact that most dynamic network modules are highly condition-specific. Finally, we note that the applicability of our algorithm is not limited to the study of PPI systems, instead it is generally applicable to the combination of any type of network and time-series data.

Abnormal expression of leiomyoma cytoskeletal proteins involved in cell migration.

Science.gov (United States)

Ura, Blendi; Scrimin, Federica; Arrigoni, Giorgio; Athanasakis, Emmanouil; Aloisio, Michelangelo; Monasta, Lorenzo; Ricci, Giuseppe

2016-05-01

Uterine leiomyomas are monoclonal tumors. Several factors are involved in the neoplastic transformation of the myometrium. In our study we focused on dysregulated cytoskeletal proteins in the leiomyoma as compared to the myometrium. Paired tissue samples of ten leiomyomas and adjacent myometria were obtained and analyzed by two‑dimensional gel electrophoresis (2-DE). Mass spectrometry was used for protein identification, and western blotting for 2-DE data validation. The values of ten cytoskeletal proteins were found to be significantly different: eight proteins were upregulated in the leiomyoma and two proteins were downregulated. Three of the upregulated proteins (myosin regulatory light polypeptide 9, four and a half LIM domains protein 1 and LIM and SH3 domain protein 1) are involved in cell migration, while downregulated protein transgelin is involved in replicative senescence. Myosin regulatory light polypeptide 9 (MYL9) was further validated by western blotting because it is considered to be a cell migration marker in several cancers and could play a key role in leiomyoma development. Our data demonstrate significant alterations in the expression of cytoskeletal proteins involved in leiomyoma growth. A better understanding of the involvement of cytoskeletal proteins in leiomyoma pathogenesis may contribute to the identification of new therapeutic targets and the development of new pharmacological approaches.

Microvillar ion channels: cytoskeletal modulation of ion fluxes.

Science.gov (United States)

Lange, K

2000-10-21

movement of the system (electro-mechanical coupling). Because ionic transmission through linear polyelectrolytes is very slow compared with electronic conduction, only low-frequency electromagnetic fields can interact with the condensed counterion systems of linear polyelectrolytes. The delineated characteristics of microvillar ion conduction are strongly supported by the phenomenon of electro-mechanical coupling (reverse transduction) in microvilli of the audioreceptor (hair) cells and the recently reported dynamics of Ca(2+)signaling in microvilli of audio- and photoreceptor cells. Due to the cell-specific expression of different types and combinations of ion channels and transporters in the microvillar tip membrane of differentiated cells, the functional properties of this cell surface organelle are highly variable serving a multitude of different cellular functions including receptor-mediated effects such as Ca(2+)signaling, regulation of glucose and amino acid transport, as well as modulation of membrane potential. Even mechanical channel activation involved in cell volume regulation can be deduced from the systematic properties of the microvillar channel concept. In addition, the specific ion conduction properties of microfilaments combined with their proposed role in Ca(2+)signaling make microvilli the most likely cellular site for the interaction with external electric and magnetic fields. Copyright 2000 Academic Press.

Modulation of neuronal dynamic range using two different adaptation mechanisms

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Lei Wang

2017-01-01

Full Text Available The capability of neurons to discriminate between intensity of external stimulus is measured by its dynamic range. A larger dynamic range indicates a greater probability of neuronal survival. In this study, the potential roles of adaptation mechanisms (ion currents in modulating neuronal dynamic range were numerically investigated. Based on the adaptive exponential integrate-and-fire model, which includes two different adaptation mechanisms, i.e. subthreshold and suprathreshold (spike-triggered adaptation, our results reveal that the two adaptation mechanisms exhibit rather different roles in regulating neuronal dynamic range. Specifically, subthreshold adaptation acts as a negative factor that observably decreases the neuronal dynamic range, while suprathreshold adaptation has little influence on the neuronal dynamic range. Moreover, when stochastic noise was introduced into the adaptation mechanisms, the dynamic range was apparently enhanced, regardless of what state the neuron was in, e.g. adaptive or non-adaptive. Our model results suggested that the neuronal dynamic range can be differentially modulated by different adaptation mechanisms. Additionally, noise was a non-ignorable factor, which could effectively modulate the neuronal dynamic range.

Cell elasticity with altered cytoskeletal architectures across multiple cell types.

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Grady, Martha E; Composto, Russell J; Eckmann, David M

2016-08-01

The cytoskeleton is primarily responsible for providing structural support, localization and transport of organelles, and intracellular trafficking. The structural support is supplied by actin filaments, microtubules, and intermediate filaments, which contribute to overall cell elasticity to varying degrees. We evaluate cell elasticity in five different cell types with drug-induced cytoskeletal derangements to probe how actin filaments and microtubules contribute to cell elasticity and whether it is conserved across cell type. Specifically, we measure elastic stiffness in primary chondrocytes, fibroblasts, endothelial cells (HUVEC), hepatocellular carcinoma cells (HUH-7), and fibrosarcoma cells (HT 1080) subjected to two cytoskeletal destabilizers: cytochalasin D and nocodazole, which disrupt actin and microtubule polymerization, respectively. Elastic stiffness is measured by atomic force microscopy (AFM) and the disruption of the cytoskeleton is confirmed using fluorescence microscopy. The two cancer cell lines showed significantly reduced elastic moduli values (~0.5kPa) when compared to the three healthy cell lines (~2kPa). Non-cancer cells whose actin filaments were disrupted using cytochalasin D showed a decrease of 60-80% in moduli values compared to untreated cells of the same origin, whereas the nocodazole-treated cells showed no change in elasticity. Overall, we demonstrate actin filaments contribute more to elastic stiffness than microtubules but this result is cell type dependent. Cancer cells behaved differently, exhibiting increased stiffness as well as stiffness variability when subjected to nocodazole. We show that disruption of microtubule dynamics affects cancer cell elasticity, suggesting therapeutic drugs targeting microtubules be monitored for significant elastic changes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hierarchical Distribution of the Tau Cytoskeletal Pathology in the Thalamus of Alzheimer's Disease Patients

NARCIS (Netherlands)

Rueb, Udo; Stratmann, Katharina; Heinsen, Helmut; Del Turco, Domenico; Ghebremedhin, Estifanos; Seidel, Kay; den Dunnen, Wilfred; Korf, Horst-Werner

2015-01-01

In spite of considerable progress in neuropathological research on Alzheimer's disease (AD), knowledge regarding the exact pathoanatomical distribution of the tau cytoskeletal pathology in the thalamus of AD patients in the advanced Braak and Braak AD stages V or VI of the cortical cytoskeletal

Zearalenone altered the cytoskeletal structure via ER stress- autophagy- oxidative stress pathway in mouse TM4 Sertoli cells.

Science.gov (United States)

Zheng, Wanglong; Wang, Bingjie; Si, Mengxue; Zou, Hui; Song, Ruilong; Gu, Jianhong; Yuan, Yan; Liu, Xuezhong; Zhu, Guoqiang; Bai, Jianfa; Bian, Jianchun; Liu, ZongPing

2018-02-20

The aim of this study was to investigate the molecular mechanisms of the destruction of cytoskeletal structure by Zearalenone (ZEA) in mouse-derived TM4 cells. In order to investigate the role of autophagy, oxidative stress and endoplasmic reticulum(ER) stress in the process of destruction of cytoskeletal structure, the effects of ZEA on the cell viability, cytoskeletal structure, autophagy, oxidative stress, ER stress, MAPK and PI3K- AKT- mTOR signaling pathways were studied. The data demonstrated that ZEA damaged the cytoskeletal structure through the induction of autophagy that leads to the alteration of cytoskeletal structure via elevated oxidative stress. Our results further showed that the autophagy was stimulated by ZEA through PI3K-AKT-mTOR and MAPK signaling pathways in TM4 cells. In addition, ZEA also induced the ER stress which was involved in the induction of the autophagy through inhibiting the ERK signal pathway to suppress the phosphorylation of mTOR. ER stress was involved in the damage of cytoskeletal structure through induction of autophagy by producing ROS. Taken together, this study revealed that ZEA altered the cytoskeletal structure via oxidative stress - autophagy- ER stress pathway in mouse TM4 Sertoli cells.

Hierarchical Distribution of the Tau Cytoskeletal Pathology in the Thalamus of Alzheimer's Disease Patients.

Science.gov (United States)

Rüb, Udo; Stratmann, Katharina; Heinsen, Helmut; Del Turco, Domenico; Ghebremedhin, Estifanos; Seidel, Kay; den Dunnen, Wilfred; Korf, Horst-Werner

2016-01-01

In spite of considerable progress in neuropathological research on Alzheimer's disease (AD), knowledge regarding the exact pathoanatomical distribution of the tau cytoskeletal pathology in the thalamus of AD patients in the advanced Braak and Braak AD stages V or VI of the cortical cytoskeletal pathology is still fragmentary. Investigation of serial 100 μm-thick brain tissue sections through the thalamus of clinically diagnosed AD patients with Braak and Braak AD stage V or VI cytoskeletal pathologies immunostained with the anti-tau AT8 antibody, along with the affection of the extraterritorial reticular nucleus of the thalamus, reveals a consistent and severe tau immunoreactive cytoskeletal pathology in the limbic nuclei of the thalamus (e.g., paraventricular, anterodorsal and laterodorsal nuclei, limitans-suprageniculate complex). The thalamic nuclei integrated into the associative networks of the human brain (e.g., ventral anterior and mediodorsal nuclei) are only mildly affected, while its motor precerebellar (ventral lateral nucleus) and sensory nuclei (e.g., lateral and medial geniculate bodies, ventral posterior medial and lateral nuclei, parvocellular part of the ventral posterior medial nucleus) are more or less spared. The highly stereotypical and characteristic thalamic distribution pattern of the AD-related tau cytoskeletal pathology represents an anatomical mirror of the hierarchical topographic distribution of the cytoskeletal pathology in the interconnected regions of the cerebral cortex of AD patients. These pathoanatomical parallels support the pathophysiological concept of a transneuronal spread of the disease process of AD along anatomical pathways. The AD-related tau cytoskeletal pathology in the thalamus most likely contributes substantially to the neuropsychiatric disease symptoms (e.g., dementia), attention deficits, oculomotor dysfunctions, altered non-discriminative aspects of pain experience of AD patients, and the disruption of their

Pressure-modulation dynamic attenuated-total-reflectance (ATR) FT-IR spectroscopy

Science.gov (United States)

Marcott, C.; Story, G. M.; Noda, I.; Bibby, A.; Manning, C. J.

1998-06-01

A single-reflectance attenuated-total-reflectance (ATR) accessory with a diamond internal-reflection element was modified by the addition of a piezoelectric transducer. Initial dynamic pressure-modulation experiments have been performed in the sample compartment of a step-scanning FT-IR spectrometer. A sinusoidal pressure modulation applied to samples of isotactic polypropylene and linear low density polyethylene resulted in dynamic responses which appear to be similar to those observed in previous dynamic 2D IR experiments. Preliminary pressure-modulation dynamic ATR results are also reported for a styrene-butadiene-styrene triblock copolymer. The new method has the advantages that a much wider variety of sample types and geometries can be studied and less sample preparation is required. Dynamic 2D IR experiments carried out by ATR no longer require thin films of large area and sufficient strength to withstand the dynamic strain applied by a rheometer. The ability to obtain dynamic IR spectroscopic information from a wider variety of sample types and thicknesses would greatly expand the amount of useful information that could be extracted from normally complicated, highly overlapped IR spectra.

Nuclear shape changes are induced by knockdown of the SWI/SNF ATPase BRG1 and are independent of cytoskeletal connections.

Directory of Open Access Journals (Sweden)

Karen M Imbalzano

Full Text Available Changes in nuclear morphology occur during normal development and have been observed during the progression of several diseases. The shape of a nucleus is governed by the balance of forces exerted by nuclear-cytoskeletal contacts and internal forces created by the structure of the chromatin and nuclear envelope. However, factors that regulate the balance of these forces and determine nuclear shape are poorly understood. The SWI/SNF chromatin remodeling enzyme ATPase, BRG1, has been shown to contribute to the regulation of overall cell size and shape. Here we document that immortalized mammary epithelial cells show BRG1-dependent nuclear shape changes. Specifically, knockdown of BRG1 induced grooves in the nuclear periphery that could be documented by cytological and ultrastructural methods. To test the hypothesis that the observed changes in nuclear morphology resulted from altered tension exerted by the cytoskeleton, we disrupted the major cytoskeletal networks and quantified the frequency of BRG1-dependent changes in nuclear morphology. The results demonstrated that disruption of cytoskeletal networks did not change the frequency of BRG1-induced nuclear shape changes. These findings suggest that BRG1 mediates control of nuclear shape by internal nuclear mechanisms that likely control chromatin dynamics.

Strong adhesion by regulatory T cells induces dendritic cell cytoskeletal polarization and contact-dependent lethargy.

Science.gov (United States)

Chen, Jiahuan; Ganguly, Anutosh; Mucsi, Ashley D; Meng, Junchen; Yan, Jiacong; Detampel, Pascal; Munro, Fay; Zhang, Zongde; Wu, Mei; Hari, Aswin; Stenner, Melanie D; Zheng, Wencheng; Kubes, Paul; Xia, Tie; Amrein, Matthias W; Qi, Hai; Shi, Yan

2017-02-01

Dendritic cells are targeted by regulatory T (T reg) cells, in a manner that operates as an indirect mode of T cell suppression. In this study, using a combination of single-cell force spectroscopy and structured illumination microscopy, we analyze individual T reg cell-DC interaction events and show that T reg cells exhibit strong intrinsic adhesiveness to DCs. This increased DC adhesion reduces the ability of contacted DCs to engage other antigen-specific cells. We show that this unusually strong LFA-1-dependent adhesiveness of T reg cells is caused in part by their low calpain activities, which normally release integrin-cytoskeleton linkage, and thereby reduce adhesion. Super resolution imaging reveals that such T reg cell adhesion causes sequestration of Fascin-1, an actin-bundling protein essential for immunological synapse formation, and skews Fascin-1-dependent actin polarization in DCs toward the T reg cell adhesion zone. Although it is reversible upon T reg cell disengagement, this sequestration of essential cytoskeletal components causes a lethargic state of DCs, leading to reduced T cell priming. Our results reveal a dynamic cytoskeletal component underlying T reg cell-mediated DC suppression in a contact-dependent manner. © 2017 Chen et al.

Role of density modulation in the spatially resolved dynamics of strongly confined liquids.

Science.gov (United States)

Saw, Shibu; Dasgupta, Chandan

2016-08-07

Confinement by walls usually produces a strong modulation in the density of dense liquids near the walls. Using molecular dynamics simulations, we examine the effects of the density modulation on the spatially resolved dynamics of a liquid confined between two parallel walls, using a resolution of a fraction of the interparticle distance in the liquid. The local dynamics is quantified by the relaxation time associated with the temporal autocorrelation function of the local density. We find that this local relaxation time varies in phase with the density modulation. The amplitude of the spatial modulation of the relaxation time can be quite large, depending on the characteristics of the wall and thermodynamic parameters of the liquid. To disentangle the effects of confinement and density modulation on the spatially resolved dynamics, we compare the dynamics of a confined liquid with that of an unconfined one in which a similar density modulation is induced by an external potential. We find several differences indicating that density modulation alone cannot account for all the features seen in the spatially resolved dynamics of confined liquids. We also examine how the dynamics near a wall depends on the separation between the two walls and show that the features seen in our simulations persist in the limit of large wall separation.

Comparison of Static and Dynamic Elastic Modules of Different Strength Concretes

Science.gov (United States)

Uyanık, Osman; Sabbaǧ, Nevbahar

2016-04-01

In this study, the static and dynamic elastic (Young) modules of concrete with different strength was intended to compare. For this purpose 150mm dimensions 9 for each design cubic samples prepared and they were subjected to water cure during 28 days. After Seismic Ultrasonic P and S wave travel time measurements of samples, P and S wave velocities and taking advantage of elasticity theory the dynamic elastic modules were calculated. Concrete strength was obtained from the uniaxial compression tests in order to calculate the static elastic modules of the samples. The static elastic modulus is calculated by using the empirical relationships used in international standards. The obtained static and dynamic elastic modules have been associated. A curve was obtained from this association result that approximately similar to the stress-strain curve of obtaining at failure criterion of the sample. This study was supported with OYP05277-DR-14 Project No. by SDU and State Hydraulic Works 13th Regional/2012-01 Project No. Keywords: Concrete Strength, P and S wave Velocities, Static, Dynamic, Young Modules

Cytoskeletal Tropomyosin Tm5NM1 Is Required for Normal Excitation–Contraction Coupling in Skeletal Muscle

OpenAIRE

Vlahovich, Nicole; Kee, Anthony J.; Van der Poel, Chris; Kettle, Emma; Hernandez-Deviez, Delia; Lucas, Christine; Lynch, Gordon S.; Parton, Robert G.; Gunning, Peter W.; Hardeman, Edna C.

2009-01-01

The functional diversity of the actin microfilaments relies in part on the actin binding protein tropomyosin (Tm). The muscle-specific Tms regulate actin-myosin interactions and hence contraction. However, there is less known about the roles of the numerous cytoskeletal isoforms. We have shown previously that a cytoskeletal Tm, Tm5NM1, defines a Z-line adjacent cytoskeleton in skeletal muscle. Recently, we identified a second cytoskeletal Tm in this region, Tm4. Here we show that Tm4 and Tm5N...

Phase dynamics of a Josephson junction ladder driven by modulated currents

International Nuclear Information System (INIS)

Kawaguchi, T.

2011-01-01

Phase dynamics of disordered Josephson junction ladders (JJLs) driven by external currents which are spatially and temporally modulated is studied using a numerical simulation based on a random field XY model. This model is considered theoretically as an effective model of JJLs with structural disorder in a magnetic field. The spatiotemporal modulation of external currents causes peculiar dynamical effects of phases in the system under certain conditions, such as the directed motion of phases and the mode-locking in the absence of dc currents. We clarify the details of effects of the spatiotemporal modulation on the phase dynamics.

An abstract machine model of dynamic module replacement

OpenAIRE

Walton, Chris; Kırlı, Dilsun; Gilmore, Stephen

2000-01-01

In this paper we define an abstract machine model for the mλ typed intermediate language. This abstract machine is used to give a formal description of the operation of run-time module replacement for the programming language Dynamic ML. The essential technical device which we employ for module replacement is a modification of two-space copying garbage collection. We show how the operation of module replacement could be applied to other garbage-collected languages such as Java.

Implementation of intensity modulation with dynamic multileaf collimation

Energy Technology Data Exchange (ETDEWEB)

Wong, J W; Yu, C; Jaffray, D [William Beaumont Hospital, Royal Oak, MI (United States)

1995-12-01

The computer-controlled multileaf collimator (MLC) marks one of the most important advances in radiation therapy. The device efficiently replaces manual blocking to shape fields and can be used to modulate beam intensity. The results of a research programme at William Beaumont Hospital, aimed at bringing dynamic intensity modulation into clinical use, are discussed.

Detection of cytoskeletal proteins in small cell lung carcinoma

Czech Academy of Sciences Publication Activity Database

Hložánková, M.; Lukáš, Z.; Viklický, Vladimír

1999-01-01

Roč. 18, - (1999), s. 47-49 ISSN 0231-5882 Grant - others:MŠk1(CZ) OE10a/EU1450 Keywords : cytoskeletal proteins * small cell lung carcinoma Subject RIV: EI - Biotechnology ; Bionics Impact factor: 0.400, year: 1999

Ultrafine particles cause cytoskeletal dysfunctions in macrophages: role of intracellular calcium

Directory of Open Access Journals (Sweden)

Brown David M

2005-10-01

Full Text Available Abstract Background Particulate air pollution is reported to cause adverse health effects in susceptible individuals. Since most of these particles are derived form combustion processes, the primary composition product is carbon with a very small diameter (ultrafine, less than 100 nm in diameter. Besides the induction of reactive oxygen species and inflammation, ultrafine particles (UFP can cause intracellular calcium transients and suppression of defense mechanisms of alveolar macrophages, such as impaired migration or phagocytosis. Methods In this study the role of intracellular calcium transients caused by UFP was studied on cytoskeleton related functions in J774A.1 macrophages. Different types of fine and ultrafine carbon black particles (CB and ufCB, respectively, such as elemental carbon (EC90, commercial carbon (Printex 90, diesel particulate matter (DEP and urban dust (UD, were investigated. Phagosome transport mechanisms and mechanical cytoskeletal integrity were studied by cytomagnetometry and cell viability was studied by fluorescence microscopy. Macrophages were exposed in vitro with 100 and 320 μg UFP/ml/million cells for 4 hours in serum free medium. Calcium antagonists Verapamil, BAPTA-AM and W-7 were used to block calcium channels in the membrane, to chelate intracellular calcium or to inhibit the calmodulin signaling pathways, respectively. Results Impaired phagosome transport and increased cytoskeletal stiffness occurred at EC90 and P90 concentrations of 100 μg/ml/million cells and above, but not with DEP or UD. Verapamil and W-7, but not BAPTA-AM inhibited the cytoskeletal dysfunctions caused by EC90 or P90. Additionally the presence of 5% serum or 1% bovine serum albumin (BSA suppressed the cytoskeletal dysfunctions. Cell viability showed similar results, where co-culture of ufCB together with Verapamil, W-7, FCS or BSA produced less cell dead compared to the particles only.

Mena associates with Rac1 and modulates connexin 43 remodeling in cardiomyocytes.

Science.gov (United States)

Ram, Rashmi; Wescott, Andrew P; Varandas, Katherine; Dirksen, Robert T; Blaxall, Burns C

2014-01-01

Mena, a member of the Ena/VASP family of actin regulatory proteins, modulates microfilaments and interacts with cytoskeletal proteins associated with heart failure. Mena is localized at the intercalated disc (ICD) of adult cardiac myocytes, colocalizing with numerous cytoskeletal proteins. Mena's role in the maintainence of mechanical myocardial stability at the cardiomyocyte ICD remains unknown. We hypothesized that Mena may modulate signals from the sarcolemma to the actin cytoskeleton at the ICD to regulate the expression and localization of connexin 43 (Cx43). The small GTPase Rac1 plays a pivotal role in the regulation of actin cytoskeletal reorganization and mediating morphological and transcriptional changes in cardiomyocytes. We found that Mena is associated with active Rac1 in cardiomyocytes and that RNAi knockdown of Mena increased Rac1 activity significantly. Furthermore, Mena knockdown increased Cx43 expression and altered Cx43 localization and trafficking at the ICD, concomitant with faster intercellular communication, as assessed by dye transfer between cardiomyocyte pairs. In mice overexpressing constitutively active Rac1, left ventricular Mena expression was increased significantly, concomitant with lateral redistribution of Cx43. These results suggest that Mena is a critical regulator of the ICD and is required for normal localization of Cx43 in part via regulation of Rac1.

Visualization of cytoskeletal elements by the atomic force microscope

International Nuclear Information System (INIS)

Berdyyeva, T.; Woodworth, C.D.; Sokolov, I.

2005-01-01

We describe a novel application of atomic force microscopy (AFM) to directly visualize cytoskeletal fibers in human foreskin epithelial cells. The nonionic detergent Triton X-100 in a low concentration was used to remove the membrane, soluble proteins, and organelles from the cell. The remaining cytoskeleton can then be directly visualized in either liquid or air-dried ambient conditions. These two types of scanning provide complimentary information. Scanning in liquid visualizes the surface filaments of the cytoskeleton, whereas scanning in air shows both the surface filaments and the total 'volume' of the cytoskeletal fibers. The smallest fibers observed were ca. 50 nm in diameter. The lateral resolution of this technique was ca.20 nm, which can be increased to a single nanometer level by choosing sharper AFM tips. Because the AFM is a true 3D technique, we are able to quantify the observed cytoskeleton by its density and volume. The types of fibers can be identified by their size, similar to electron microscopy

Actin dynamics and the elasticity of cytoskeletal networks

Directory of Open Access Journals (Sweden)

2009-09-01

Full Text Available The structural integrity of a cell depends on its cytoskeleton, which includes an actin network. This network is transient and depends upon the continual polymerization and depolymerization of actin. The degradation of an actin network, and a corresponding reduction in cell stiffness, can indicate the presence of disease. Numerical simulations will be invaluable for understanding the physics of these systems and the correlation between actin dynamics and elasticity. Here we develop a model that is capable of generating actin network structures. In particular, we develop a model of actin dynamics which considers the polymerization, depolymerization, nucleation, severing, and capping of actin filaments. The structures obtained are then fed directly into a mechanical model. This allows us to qualitatively assess the effects of changing various parameters associated with actin dynamics on the elasticity of the material.

Dynamic Aperture Extrapolation in Presence of Tune Modulation

CERN Document Server

Giovannozzi, Massimo; Todesco, Ezio

1998-01-01

In hadron colliders, such as the Large Hadron Collider (LHC) to be built at CERN, the long-term stability of the single-particle motion is mostly determined by the field-shape quality of the superconducting magnets. The mechanism of particle loss may be largely enhanced by modulation of betatron tunes, induced either by synchro-betatron coupling (via the residual uncorrected chromaticity), or by unavoidable power supply ripple. This harmful effect is investigated in a simple dynamical system model, the Henon map with modulated linear frequencies. Then, a realistic accelerator model describing the injection optics of the LHC lattice is analyzed. Orbital data obtained with long-term tracking simulations ($10^5$-$10^7$ turns) are post-processed to obtain the dynamic aperture. It turns out that the dynamic aperture can be interpolated using a simple mpirical formula, and it decays proportionally to a power of the inverse logarithm of the number of turns. Furthermore, the extrapolation of tracking data at $10^5$ t...

Cooperation of the BTB-Zinc finger protein, Abrupt, with cytoskeletal regulators in Drosophila epithelial tumorigenesis

Directory of Open Access Journals (Sweden)

Nezaket Turkel

2015-08-01

Full Text Available The deregulation of cell polarity or cytoskeletal regulators is a common occurrence in human epithelial cancers. Moreover, there is accumulating evidence in human epithelial cancer that BTB-ZF genes, such as Bcl6 and ZBTB7A, are oncogenic. From our previous studies in the vinegar fly, Drosophila melanogaster, we have identified a cooperative interaction between a mutation in the apico-basal cell polarity regulator Scribble (Scrib and overexpression of the BTB-ZF protein Abrupt (Ab. Herein, we show that co-expression of ab with actin cytoskeletal regulators, RhoGEF2 or Src64B, in the developing eye-antennal epithelial tissue results in the formation of overgrown amorphous tumours, whereas ab and DRac1 co-expression leads to non-cell autonomous overgrowth. Together with ab, these genes affect the expression of differentiation genes, resulting in tumours locked in a progenitor cell fate. Finally, we show that the expression of two mammalian genes related to ab, Bcl6 and ZBTB7A, which are oncogenes in mammalian epithelial cancers, significantly correlate with the upregulation of cytoskeletal genes or downregulation of apico-basal cell polarity neoplastic tumour suppressor genes in colorectal, lung and other human epithelial cancers. Altogether, this analysis has revealed that upregulation of cytoskeletal regulators cooperate with Abrupt in Drosophila epithelial tumorigenesis, and that high expression of human BTB-ZF genes, Bcl6 and ZBTB7A, shows significant correlations with cytoskeletal and cell polarity gene expression in specific epithelial tumour types. This highlights the need for further investigation of the cooperation between these genes in mammalian systems.

Cytoskeletal remodeling of connective tissue fibroblasts in response to static stretch is dependent on matrix material properties

Science.gov (United States)

Abbott, Rosalyn D; Koptiuch, Cathryn; Iatridis, James C; Howe, Alan K; Badger, Gary J; Langevin, Helene M

2012-01-01

In areolar “loose” connective tissue, fibroblasts remodel their cytoskeleton within minutes in response to static stretch resulting in increased cell body cross-sectional area that relaxes the tissue to a lower state of resting tension. It remains unknown whether the loosely arranged collagen matrix, characteristic of areolar connective tissue, is required for this cytoskeletal response to occur. The purpose of this study was to evaluate cytoskeletal remodeling of fibroblasts in and dissociated from areolar and dense connective tissue in response to 2 hours of static stretch in both native tissue and collagen gels of varying crosslinking. Rheometric testing indicated that the areolar connective tissue had a lower dynamic modulus and was more viscous than the dense connective tissue. In response to stretch, cells within the more compliant areolar connective tissue adopted a large “sheet-like” morphology that was in contrast to the smaller dendritic morphology in the dense connective tissue. By adjusting the in vitro collagen crosslinking, and the resulting dynamic modulus, it was demonstrated that cells dissociated from dense connective tissue are capable of responding when seeded into a compliant matrix, while cells dissociated from areolar connective tissue can lose their ability to respond when their matrix becomes stiffer. This set of experiments indicated stretch-induced fibroblast expansion was dependent on the distinct matrix material properties of areolar connective tissues as opposed to the cells’ tissue of origin. These results also suggest that disease and pathological processes with increased crosslinks, such as diabetes and fibrosis, could impair fibroblast responsiveness in connective tissues. PMID:22552950

Dynamic range in BOLD modulation: lifespan aging trajectories and association with performance.

Science.gov (United States)

Kennedy, Kristen M; Boylan, Maria A; Rieck, Jenny R; Foster, Chris M; Rodrigue, Karen M

2017-12-01

Alteration of dynamic range of modulation to cognitive difficulty has been proposed as a salient predictor of cognitive aging. Here, we examine in 171 adults (aged 20-94 years) the effects of age on dynamic modulation of blood oxygenation-level dependent activation to difficulty in parametrically increasing working memory (WM) load (0-, 2-, 3-, and 4-back conditions). First, we examined parametric increases and decreases in activation to increasing WM load (positive modulation effect and negative modulation effect). Second, we examined the effect of age on modulation to difficulty (WM load) to identify regions that differed with age as difficulty increased (age-related positive and negative modulation effects). Weakened modulation to difficulty with age was found in both the positive modulation (middle frontal, superior/inferior parietal) and negative modulation effect (deactivated) regions (insula, cingulate, medial superior frontal, fusiform, and parahippocampal gyri, hippocampus, and lateral occipital cortex). Age-related alterations to positive modulation emerged later in the lifespan than negative modulation. Furthermore, these effects were significantly coupled in that greater upmodulation was associated with lesser downmodulation. Importantly, greater fronto-parietal upmodulation to difficulty and greater downmodulation of deactivated regions were associated with better task accuracy and upmodulation with better WM span measured outside the scanner. These findings suggest that greater dynamic range of modulation of activation to cognitive challenge is in service of current task performance, as well as generalizing to cognitive ability beyond the scanner task, lending support to its utility as a marker of successful cognitive aging. Copyright © 2017 Elsevier Inc. All rights reserved.

Module type plant system dynamics analysis code (MSG-COPD). Code manual

International Nuclear Information System (INIS)

Sakai, Takaaki

2002-11-01

MSG-COPD is a module type plant system dynamics analysis code which involves a multi-dimensional thermal-hydraulics calculation module to analyze pool type of fast breeder reactors. Explanations of each module and the methods for the input data are described in this code manual. (author)

Milk fat globule-epidermal growth factor-factor VIII-derived peptide MSP68 is a cytoskeletal immunomodulator of neutrophils that inhibits Rac1.

Science.gov (United States)

Hendricks, Louie; Aziz, Monowar; Yang, Weng-Lang; Nicastro, Jeffrey; Coppa, Gene F; Symons, Marc; Wang, Ping

2017-02-01

Prolonged neutrophil infiltration leads to exaggerated inflammation and tissue damage during sepsis. Neutrophil migration requires rearrangement of their cytoskeleton. Milk fat globule-epidermal growth factor-factor VIII-derived short peptide 68 (MSP68) has recently been shown to be beneficial in sepsis-induced tissue injury and mortality. We hypothesize that MSP68 inhibits neutrophil migration by modulating small GTPase Rac1-dependent cytoskeletal rearrangements. Bone marrow-derived neutrophils (BMDNs) or whole lung digest isolated neutrophils were isolated from 8 to 10 wk old C57BL/6 mice by Percoll density gradient centrifugation. The purity of BMDN was verified by flow cytometry with CD11b/Gr-1 staining. Neutrophils were stimulated with N-formylmethionine-leucine-phenylalanine (f-MLP) (10 nM) in the presence or absence of MSP68 at 10 nM or cecal ligation and puncture (CLP) was used to induce sepsis, and MSP68 was administered at 1 mg/kg intravenously. Cytoskeletal organization was assessed by phalloidin staining, followed by analysis using fluorescence microscopy. Activity of the Rac1 GTPase in f-MLP or CLP-activated BMDN in the presence or absence of MSP68 was assessed by GTPase enzyme-linked immunosorbent assay. Mitogen-activated protein (MAP) kinase activity was determined by western blot densitometry. BMDN treatment with f-MLP increased cytoskeletal remodeling as revealed by the localization of filamentous actin to the periphery of the neutrophil. By contrast, cells pretreated with MSP68 had considerably reduced filamentous actin polymerization. Cytoskeletal spreading is associated with the activation of the small GTPase Rac1. We found BMDN-treated with f-MLP or that were exposed to sepsis by CLP had increased Rac1 signaling, whereas the cells pretreated with MSP68 had significantly reduced Rac1 activation (P Rac1-MAP kinase-mediated neutrophil motility. Thus, MSP68 is a novel therapeutic candidate for regulating inflammation and tissue damage caused

Nanosecond electric pulses modulate skeletal muscle calcium dynamics and contraction

Science.gov (United States)

Valdez, Chris; Jirjis, Michael B.; Roth, Caleb C.; Barnes, Ronald A.; Ibey, Bennett L.

2017-02-01

Irreversible electroporation therapy is utilized to remove cancerous tissues thru the delivery of rapid (250Hz) and high voltage (V) (1,500V/cm) electric pulses across microsecond durations. Clinical research demonstrated that bipolar (BP) high voltage microsecond pulses opposed to monophasic waveforms relieve muscle contraction during electroporation treatment. Our group along with others discovered that nanosecond electric pulses (nsEP) can activate second messenger cascades, induce cytoskeletal rearrangement, and depending on the nsEP duration and frequency, initiate apoptotic pathways. Of high interest across in vivo and in vitro applications, is how nsEP affects muscle physiology, and if nuances exist in comparison to longer duration electroporation applications. To this end, we exposed mature skeletal muscle cells to monopolar (MP) and BP nsEP stimulation across a wide range of electric field amplitudes (1-20 kV/cm). From live confocal microscopy, we simultaneously monitored intracellular calcium dynamics along with nsEP-induced muscle movement on a single cell level. In addition, we also evaluated membrane permeability with Yo-PRO-1 and Propidium Iodide (PI) across various nsEP parameters. The results from our findings suggest that skeletal muscle calcium dynamics, and nsEP-induced contraction exhibit exclusive responses to both MP and BP nsEP exposure. Overall the results suggest in vivo nsEP application may elicit unique physiology and field applications compared to longer pulse duration electroporation.

Pulsewidth modulated DC-to-DC power conversion circuits, dynamics, and control designs

CERN Document Server

Choi, Byungcho

2013-01-01

This is the definitive reference for anyone involved in pulsewidth modulated DC-to-DC power conversion Pulsewidth Modulated DC-to-DC Power Conversion: Circuits, Dynamics, and Control Designs provides engineers, researchers, and students in the power electronics field with comprehensive and complete guidance to understanding pulsewidth modulated (PWM) DC-to-DC power converters. Presented in three parts, the book addresses the circuitry and operation of PWM DC-to-DC converters and their dynamic characteristics, along with in-depth discussions of control design of PWM DC-to

Antibodies to cytoskeletal proteins as evidenced by immunofluorescence microscopy and radioimmunoassay

International Nuclear Information System (INIS)

Zugehoer, M.; Struy, H.; Morenz, J.

1987-01-01

In patients suffering from chronic hepatitis, collagenosis and infectious mononucleosis, resp., as well as in blood donors antibodies against cytoskeletal antigens such as actin, myosin, actinin, desmin, keratin, and tubulin were determined by radioimmunoassay

Antibodies to cytoskeletal proteins as evidenced by immunofluorescence microscopy and radioimmunoassay

Energy Technology Data Exchange (ETDEWEB)

Zugehoer, M; Struy, H; Morenz, J

1987-01-01

In patients suffering from chronic hepatitis, collagenosis and infectious mononucleosis, resp., as well as in blood donors antibodies against cytoskeletal antigens such as actin, myosin, actinin, desmin, keratin, and tubulin were determined by radioimmunoassay.

Random and systematic beam modulator errors in dynamic intensity modulated radiotherapy

International Nuclear Information System (INIS)

Parsai, Homayon; Cho, Paul S; Phillips, Mark H; Giansiracusa, Robert S; Axen, David

2003-01-01

This paper reports on the dosimetric effects of random and systematic modulator errors in delivery of dynamic intensity modulated beams. A sliding-widow type delivery that utilizes a combination of multileaf collimators (MLCs) and backup diaphragms was examined. Gaussian functions with standard deviations ranging from 0.5 to 1.5 mm were used to simulate random positioning errors. A clinical example involving a clival meningioma was chosen with optic chiasm and brain stem as limiting critical structures in the vicinity of the tumour. Dose calculations for different modulator fluctuations were performed, and a quantitative analysis was carried out based on cumulative and differential dose volume histograms for the gross target volume and surrounding critical structures. The study indicated that random modulator errors have a strong tendency to reduce minimum target dose and homogeneity. Furthermore, it was shown that random perturbation of both MLCs and backup diaphragms in the order of σ = 1 mm can lead to 5% errors in prescribed dose. In comparison, when MLCs or backup diaphragms alone was perturbed, the system was more robust and modulator errors of at least σ = 1.5 mm were required to cause dose discrepancies greater than 5%. For systematic perturbation, even errors in the order of ±0.5 mm were shown to result in significant dosimetric deviations

Dynamic functional modules in co-expressed protein interaction networks of dilated cardiomyopathy

Directory of Open Access Journals (Sweden)

Oyang Yen-Jen

2010-10-01

Full Text Available Abstract Background Molecular networks represent the backbone of molecular activity within cells and provide opportunities for understanding the mechanism of diseases. While protein-protein interaction data constitute static network maps, integration of condition-specific co-expression information provides clues to the dynamic features of these networks. Dilated cardiomyopathy is a leading cause of heart failure. Although previous studies have identified putative biomarkers or therapeutic targets for heart failure, the underlying molecular mechanism of dilated cardiomyopathy remains unclear. Results We developed a network-based comparative analysis approach that integrates protein-protein interactions with gene expression profiles and biological function annotations to reveal dynamic functional modules under different biological states. We found that hub proteins in condition-specific co-expressed protein interaction networks tended to be differentially expressed between biological states. Applying this method to a cohort of heart failure patients, we identified two functional modules that significantly emerged from the interaction networks. The dynamics of these modules between normal and disease states further suggest a potential molecular model of dilated cardiomyopathy. Conclusions We propose a novel framework to analyze the interaction networks in different biological states. It successfully reveals network modules closely related to heart failure; more importantly, these network dynamics provide new insights into the cause of dilated cardiomyopathy. The revealed molecular modules might be used as potential drug targets and provide new directions for heart failure therapy.

Diversity of Histologic Patterns and Expression of Cytoskeletal Proteins in Canine Skeletal Osteosarcoma.

Science.gov (United States)

Nagamine, E; Hirayama, K; Matsuda, K; Okamoto, M; Ohmachi, T; Kadosawa, T; Taniyama, H

2015-09-01

Osteosarcoma (OS), the most common bone tumor, includes OS of the head (OSH) and appendicular OS (OSA). In dogs, it is classified into 6 histologic subtypes: osteoblastic, chondroblastic, fibroblastic, telangiectatic, giant cell, and poorly differentiated. This study investigated the significance of the histologic classification relevant to clinical outcome and the histologic and immunohistochemical relationships between pleomorphism and expression of cytoskeletal proteins in 60 cases each of OSH and OSA. Most neoplasms exhibited histologic diversity, and 64% of OS contained multiple subtypes. In addition to the above 6 subtypes, myxoid, round cell, and epithelioid subtypes were observed. Although the epithelioid subtypes were observed in only OSH, no significant difference in the frequency of other subtypes was observed. Also, no significant relevance was observed between the clinical outcome and histologic subtypes. Cytokeratin (CK) was expressed in both epithelioid and sarcomatoid tumor cells in various subtypes, and all CK-positive tumor cells also expressed vimentin. Vimentin and α-smooth muscle actin (SMA) were expressed in all subtypes. A few SMA-positive spindle-shaped tumor cells exhibited desmin expression. Glial fibrillary acidic protein-positive tumor cells were observed in many subtypes, and some of these cells showed neurofilament expression. Although OSH exhibited significantly stronger immunoreactivity for SMA than OSA, no significant difference in other cytoskeletal proteins was observed. Some tumor cells had cytoskeletal protein expression compatible with the corresponding histologic subtypes, such as CK in the epithelioid subtype and SMA in the fibroblastic subtype. Thus, canine skeletal OS is composed of pleomorphic and heterogenous tumor cells as is reflected in the diversity of histologic patterns and expression of cytoskeletal proteins. © The Author(s) 2015.

Hypertrophic stimulation increases beta-actin dynamics in adult feline cardiomyocytes.

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Sundaravadivel Balasubramanian

2010-07-01

Full Text Available The myocardium responds to hemodynamic stress through cellular growth and organ hypertrophy. The impact of cytoskeletal elements on this process, however, is not fully understood. While alpha-actin in cardiomyocytes governs muscle contraction in combination with the myosin motor, the exact role of beta-actin has not been established. We hypothesized that in adult cardiomyocytes, as in non-myocytes, beta-actin can facilitate cytoskeletal rearrangement within cytoskeletal structures such as Z-discs. Using a feline right ventricular pressure overload (RVPO model, we measured the level and distribution of beta-actin in normal and pressure overloaded myocardium. Resulting data demonstrated enriched levels of beta-actin and enhanced translocation to the Triton-insoluble cytoskeletal and membrane skeletal complexes. In addition, RVPO in vivo and in vitro hypertrophic stimulation with endothelin (ET or insulin in isolated adult cardiomyocytes enhanced the content of polymerized fraction (F-actin of beta-actin. To determine the localization and dynamics of beta-actin, we adenovirally expressed GFP-tagged beta-actin in isolated adult cardiomyocytes. The ectopically expressed beta-actin-GFP localized to the Z-discs, costameres, and cell termini. Fluorescence recovery after photobleaching (FRAP measurements of beta-actin dynamics revealed that beta-actin at the Z-discs is constantly being exchanged with beta-actin from cytoplasmic pools and that this exchange is faster upon hypertrophic stimulation with ET or insulin. In addition, in electrically stimulated isolated adult cardiomyocytes, while beta-actin overexpression improved cardiomyocyte contractility, immunoneutralization of beta-actin resulted in a reduced contractility suggesting that beta-actin could be important for the contractile function of adult cardiomyocytes. These studies demonstrate the presence and dynamics of beta-actin in the adult cardiomyocyte and reinforce its usefulness in measuring

NKCC1 Regulates Migration Ability of Glioblastoma Cells by Modulation of Actin Dynamics and Interacting with Cofilin

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Paula Schiapparelli

2017-07-01

Full Text Available Glioblastoma (GBM is the most aggressive primary brain tumor in adults. The mechanisms that confer GBM cells their invasive behavior are poorly understood. The electroneutral Na+-K+-2Cl− co-transporter 1 (NKCC1 is an important cell volume regulator that participates in cell migration. We have shown that inhibition of NKCC1 in GBM cells leads to decreased cell migration, in vitro and in vivo. We now report on the role of NKCC1 on cytoskeletal dynamics. We show that GBM cells display a significant decrease in F-actin content upon NKCC1 knockdown (NKCC1-KD. To determine the potential actin-regulatory mechanisms affected by NKCC1 inhibition, we studied NKCC1 protein interactions. We found that NKCC1 interacts with the actin-regulating protein Cofilin-1 and can regulate its membrane localization. Finally, we analyzed whether NKCC1 could regulate the activity of the small Rho-GTPases RhoA and Rac1. We observed that the active forms of RhoA and Rac1 were decreased in NKCC1-KD cells. In summary, we report that NKCC1 regulates GBM cell migration by modulating the cytoskeleton through multiple targets including F-actin regulation through Cofilin-1 and RhoGTPase activity. Due to its essential role in cell migration NKCC1 may serve as a specific therapeutic target to decrease cell invasion in patients with primary brain cancer.

Verification and Validation of the New Dynamic Mooring Modules Available in FAST v8: Preprint

Energy Technology Data Exchange (ETDEWEB)

Wendt, Fabian; Robertson, Amy; Jonkman, Jason; Andersen, Morten T.

2016-08-01

The open-source aero-hydro-servo-elastic wind turbine simulation software, FAST v8, was recently coupled to two newly developed mooring dynamics modules: MoorDyn and FEAMooring. MoorDyn is a lumped-mass-based mooring dynamics module developed by the University of Maine, and FEAMooring is a finite-element-based mooring dynamics module developed by Texas A&M University. This paper summarizes the work performed to verify and validate these modules against other mooring models and measured test data to assess their reliability and accuracy. The quality of the fairlead load predictions by the open-source mooring modules MoorDyn and FEAMooring appear to be largely equivalent to what is predicted by the commercial tool OrcaFlex. Both mooring dynamic model predictions agree well with the experimental data, considering the given limitations in the accuracy of the platform hydrodynamic load calculation and the quality of the measurement data.

Design of Simulink module for dynamic reactivity simulation of marine reactor automatic control rod

International Nuclear Information System (INIS)

Chen Zhiyun; Luo Lei; Chen Wenzhen; Gui Xuewen

2010-01-01

The power of marine reactor varies frequently and acutely, which induces the frequent and acute adjustment of the automatic control rod. According to the characteristics of marine reactor and the problem of improper control rod reactivity insertion in previous literatures, the Simulink module for dynamic reactivity simulation of automatic control rod was designed and adopted as a sub-module of Simulink program for the fast calculation of the physical and thermal parameters of marine reactor. A typical dynamic process of the marine reactor was used as the benchmark, which indicates that the designed Simulink module is capable of the dynamic simulation of automatic control rod position and reactivity, and is adequate to the fast calculation of physic and thermal parameters. The Simulink module is of significant meaning to the simulation of the dynamic process of marine reactor and the fast calculation of the operating parameters. (authors)

Tune modulation due to synchrotron oscillations and chromaticity, and the dynamic aperture

International Nuclear Information System (INIS)

Parzen, G.

1995-01-01

A tracking study was done of the effects of a tune modulations, due to synchrotron oscillations and the tune dependence on momentum (chromaticity), on the dynamic aperture. The studies were done using several RHIC lattices and tracking runs of about 1 x 10 6 turns. The dynamic aperture was found to decrease roughly linearly with the amplitude of the tune modulation. Lower order non-linear resonances, like the 1/3 and 1/4 resonance are not crossed because of the tune modulation. Three different cases were studied, corresponding to RHIC lattices with different β*, and with different synchrotron oscillation amplitudes. In each case, the tune modulation amplitude was varied by changing the chromaticity. In each case, roughly the same result, was found. The result found here for the effect of a tune modulation due to chromaticity may be compared with the result found for the effect of a tune modulation due to a gradient ripple in the quadrupoles. The effect of a tune modulation due to a gradient ripple appears to be about 4 times stronger than the effect of a tune modulation due to chromaticity and synchrotron oscillations

Acute fluoride poisoning alters myocardial cytoskeletal and AMPK signaling proteins in rats.

Science.gov (United States)

Panneerselvam, Lakshmikanthan; Raghunath, Azhwar; Perumal, Ekambaram

2017-02-15

Our previous findings revealed that increased oxidative stress, apoptosis and necrosis were implicated in acute fluoride (F - ) induced cardiac dysfunction apart from hypocalcemia and hyperkalemia. Cardiac intermediate filaments (desmin and vimentin) and cytoskeleton linker molecule vinculin plays an imperative role in maintaining the architecture of cardiac cytoskeleton. In addition, AMPK is a stress activated kinase that regulates the energy homeostasis during stressed state. The present study was aimed to examine the role of cytoskeletal proteins and AMPK signaling molecules in acute F - induced cardiotoxicity in rats. In order to study this, male Wistar rats were treated with single oral doses of 45 and 90mg/kgF - for 24h. Acute F - intoxicated rats showed declined cytoskeletal protein expression of desmin, vimentin and vinculin in a dose dependent manner compared to control. A significant increase in phosphorylation of AMPKα (Thr172), AMPKß1 (Ser108) and Acetyl-coA carboxylase (ACC) (Ser79) in the myocardium and associated ATP deprivation were found in acute F - intoxicated rats. Further, ultra-structural studies confirmed myofibril lysis with interruption of Z lines, dilated sarcoplasmic reticulum and damaged mitochondrion were observed in both the groups of F - intoxicated rats. Taken together, these findings reveal that acute F - exposure causes sudden heart failure by altering the expression of cytoskeletal proteins and AMPK signaling molecules. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Verification and Validation of the New Dynamic Mooring Modules Available in FAST v8

DEFF Research Database (Denmark)

Wendt, Fabian F.; Andersen, Morten Thøtt; Robertson, Amy N.

2016-01-01

The open-source, aero-hydro-servo-elastic wind turbine simulation software FAST v8 (created by the National Renewable Energy Laboratory) was recently coupled to two newly developed mooring dynamics modules: MoorDyn and FEAMooring. MoorDyn is a lumped-mass-based mooring dynamics module developed b...

Cytoskeletal dynamics

DEFF Research Database (Denmark)

Bendix, Pól Martin

2015-01-01

I worked with reconstitutted contractile acto-myosin systems containing mainly actin, actin cross-linkers and myosin motors. Contractility and rheology of such systems was studied using confocal microscopy and rheology.......I worked with reconstitutted contractile acto-myosin systems containing mainly actin, actin cross-linkers and myosin motors. Contractility and rheology of such systems was studied using confocal microscopy and rheology....

Dynamic simulator for nuclear power plants (DSNP): development, verification, and expansion of modules

International Nuclear Information System (INIS)

Larson, H.A.; Dean, E.M.; Koenig, J.F.; Gale, J.G.; Lehto, W.K.

1984-01-01

The DSNP Simulation Language facilitates whole reactor plant simulation and design. Verification includes DSNP dynamic modeling of Experimental Breeder Reactor No. 2 (EBR-II) plant experiments as well as comparisons with verified simulation programs. Great flexibility is allowed in expanding the DSNP language and accommodate other computer languages. The component modules of DSNP, contained in libraries, are continually updated with new, improved, and verified modules. The modules are used to simulate the dynamic response of LMFBR reactor systems to upset and transient conditions, with special emphasis on investigations of inherent shutdown mechanisms

Actin grips: circular actin-rich cytoskeletal structures that mediate the wrapping of polymeric microfibers by endothelial cells.

Science.gov (United States)

Jones, Desiree; Park, DoYoung; Anghelina, Mirela; Pécot, Thierry; Machiraju, Raghu; Xue, Ruipeng; Lannutti, John J; Thomas, Jessica; Cole, Sara L; Moldovan, Leni; Moldovan, Nicanor I

2015-06-01

Interaction of endothelial-lineage cells with three-dimensional substrates was much less studied than that with flat culture surfaces. We investigated the in vitro attachment of both mature endothelial cells (ECs) and of less differentiated EC colony-forming cells to poly-ε-capro-lactone (PCL) fibers with diameters in 5-20 μm range ('scaffold microfibers', SMFs). We found that notwithstanding the poor intrinsic adhesiveness to PCL, both cell types completely wrapped the SMFs after long-term cultivation, thus attaining a cylindrical morphology. In this system, both EC types grew vigorously for more than a week and became increasingly more differentiated, as shown by multiplexed gene expression. Three-dimensional reconstructions from multiphoton confocal microscopy images using custom software showed that the filamentous (F) actin bundles took a conspicuous ring-like organization around the SMFs. Unlike the classical F-actin-containing stress fibers, these rings were not associated with either focal adhesions or intermediate filaments. We also demonstrated that plasma membrane boundaries adjacent to these circular cytoskeletal structures were tightly yet dynamically apposed to the SMFs, for which reason we suggest to call them 'actin grips'. In conclusion, we describe a particular form of F-actin assembly with relevance for cytoskeletal organization in response to biomaterials, for endothelial-specific cell behavior in vitro and in vivo, and for tissue engineering. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characterization of cytoskeletal and junctional proteins expressed by cells cultured from human arachnoid granulation tissue

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Mehta Bhavya C

2005-10-01

Full Text Available Abstract Background The arachnoid granulations (AGs are projections of the arachnoid membrane into the dural venous sinuses. They function, along with the extracranial lymphatics, to circulate the cerebrospinal fluid (CSF to the systemic venous circulation. Disruption of normal CSF dynamics may result in increased intracranial pressures causing many problems including headaches and visual loss, as in idiopathic intracranial hypertension and hydrocephalus. To study the role of AGs in CSF egress, we have grown cells from human AG tissue in vitro and have characterized their expression of those cytoskeletal and junctional proteins that may function in the regulation of CSF outflow. Methods Human AG tissue was obtained at autopsy, and explanted to cell culture dishes coated with fibronectin. Typically, cells migrated from the explanted tissue after 7–10 days in vitro. Second or third passage cells were seeded onto fibronectin-coated coverslips at confluent densities and grown to confluency for 7–10 days. Arachnoidal cells were tested using immunocytochemical methods for the expression of several common cytoskeletal and junctional proteins. Second and third passage cultures were also labeled with the common endothelial markers CD-31 or VE-cadherin (CD144 and their expression was quantified using flow cytometry analysis. Results Confluent cultures of arachnoidal cells expressed the intermediate filament protein vimentin. Cytokeratin intermediate filaments were expressed variably in a subpopulation of cells. The cultures also expressed the junctional proteins connexin43, desmoplakin 1 and 2, E-cadherin, and zonula occludens-1. Flow cytometry analysis indicated that second and third passage cultures failed to express the endothelial cell markers CD31 or VE-cadherin in significant quantities, thereby showing that these cultures did not consist of endothelial cells from the venous sinus wall. Conclusion To our knowledge, this is the first report of

Unique expression of cytoskeletal proteins in human soft palate muscles.

Science.gov (United States)

Shah, Farhan; Berggren, Diana; Holmlund, Thorbjörn; Levring Jäghagen, Eva; Stål, Per

2016-03-01

The human oropharyngeal muscles have a unique anatomy with diverse and intricate functions. To investigate if this specialization is also reflected in the cytoarchitecture of muscle fibers, intermediate filament proteins and the dystrophin-associated protein complex have been analyzed in two human palate muscles, musculus uvula (UV) and musculus palatopharyngeus (PP), with immunohistochenmical and morphological techniques. Human limb muscles were used as reference. The findings show that the soft palate muscle fibers have a cytoskeletal architecture that differs from the limb muscles. While all limb muscles showed immunoreaction for a panel of antibodies directed against different domains of cytoskeletal proteins desmin and dystrophin, a subpopulation of palate muscle fibers lacked or had a faint immunoreaction for desmin (UV 11.7% and PP 9.8%) and the C-terminal of the dystrophin molecule (UV 4.2% and PP 6.4%). The vast majority of these fibers expressed slow contractile protein myosin heavy chain I. Furthermore, an unusual staining pattern was also observed in these fibers for β-dystroglycan, caveolin-3 and neuronal nitric oxide synthase nNOS, which are all membrane-linking proteins associated with the dystrophin C-terminus. While the immunoreaction for nNOS was generally weak or absent, β-dystroglycan and caveolin-3 showed a stronger immunostaining. The absence or a low expression of cytoskeletal proteins otherwise considered ubiquitous and important for integration and contraction of muscle cells indicate a unique cytoarchitecture designed to meet the intricate demands of the upper airway muscles. It can be concluded that a subgroup of muscle fibers in the human soft palate appears to have special biomechanical properties, and their unique cytoarchitecture must be taken into account while assessing function and pathology in oropharyngeal muscles. © 2015 Anatomical Society.

Apicomplexans pulling the strings: manipulation of the host cell cytoskeleton dynamics.

Science.gov (United States)

Cardoso, Rita; Soares, Helena; Hemphill, Andrew; Leitão, Alexandre

2016-07-01

Invasive stages of apicomplexan parasites require a host cell to survive, proliferate and advance to the next life cycle stage. Once invasion is achieved, apicomplexans interact closely with the host cell cytoskeleton, but in many cases the different species have evolved distinct mechanisms and pathways to modulate the structural organization of cytoskeletal filaments. The host cell cytoskeleton is a complex network, largely, but not exclusively, composed of microtubules, actin microfilaments and intermediate filaments, all of which are modulated by associated proteins, and it is involved in diverse functions including maintenance of cell morphology and mechanical support, migration, signal transduction, nutrient uptake, membrane and organelle trafficking and cell division. The ability of apicomplexans to modulate the cytoskeleton to their own advantage is clearly beneficial. We here review different aspects of the interactions of apicomplexans with the three main cytoskeletal filament types, provide information on the currently known parasite effector proteins and respective host cell targets involved, and how these interactions modulate the host cell physiology. Some of these findings could provide novel targets that could be exploited for the development of preventive and/or therapeutic strategies.

Dynamical investigation of modulated Kepler RR Lyrae stars

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Plachy E.

2015-01-01

Full Text Available We performed a non-linear dynamical analysis on the Blazhko modulation for the first time. Our results suggest that the detection of chaotic nature behind the phenomenon is limited by the instrumental effects and the data processing problems of the Kepler pipeline concerning high-amplitude variable stars.

On modulated complex non-linear dynamical systems

International Nuclear Information System (INIS)

Mahmoud, G.M.; Mohamed, A.A.; Rauh, A.

1999-01-01

This paper is concerned with the development of an approximate analytical method to investigate periodic solutions and their stability in the case of modulated non-linear dynamical systems whose equation of motion is describe. Such differential equations appear, for example, in problems of colliding particle beams in high-energy accelerators or one-mass systems with two or more degrees of freedom, e.g. rotors. The significance of periodic solutions lies on the fact that all non-periodic responses, if convergent, would approach to periodic solutions at the steady-state conditions. The example shows a good agreement between numerical and analytical results for small values of ε. The effect of the periodic modulation on the stability of the 2π-periodic solutions is discussed

Attenuation of LDHA expression in cancer cells leads to redox-dependent alterations in cytoskeletal structure and cell migration.

Science.gov (United States)

Arseneault, Robert; Chien, Andrew; Newington, Jordan T; Rappon, Tim; Harris, Richard; Cumming, Robert C

2013-09-28

Aerobic glycolysis, the preferential use of glycolysis even in the presence of oxygen to meet cellular metabolic demands, is a near universal feature of cancer. This unique type of metabolism is thought to protect cancer cells from damaging reactive oxygen species (ROS) produced in the mitochondria. Using the cancer cell line MDA-MB-435 it is shown that shRNA mediated knockdown of lactate dehydrogenase A (LDHA), a key mediator of aerobic glycolysis, results in elevated mitochondrial ROS production and a concomitant decrease in cell proliferation and motility. Redox-sensitive proteins affected by oxidative stress associated with LDHA knockdown were identified by Redox 2D-PAGE and mass spectrometry. In particular, tropomyosin (Tm) isoforms Tm4, Tm5NM1 and Tm5NM5, proteins involved in cell migration and cytoskeletal dynamics, exhibited changes in disulfide bonding and co-localized with peri-nuclear actin aggregates in LDHA knockdown cells. In contrast, treatment with the thiol-based antioxidant N-acetylcysteine promoted the relocalization of Tms to cortical actin microfilaments and partially rescued the migration defects associated with attenuated LDHA expression. These results suggest that aerobic glycolysis and reduced mitochondrial ROS production create an environment conducive to cytoskeletal remodeling; key events linked to the high cell motility associated with cancer. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Proteomic and Microscopic Strategies towards the Analysis of the Cytoskeletal Networks in Major Neuropsychiatric Disorders

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Joëlle V. F. Coumans

2016-04-01

Full Text Available Mental health disorders have become worldwide health priorities. It is estimated that in the next 20 years they will account for a 16 trillion United State dollars (US$ loss. Up to now, the underlying pathophysiology of psychiatric disorders remains elusive. Altered cytoskeleton proteins expression that may influence the assembly, organization and maintenance of cytoskeletal integrity has been reported in major depressive disorders, schizophrenia and to some extent bipolar disorders. The use of quantitative proteomics, dynamic microscopy and super-resolution microscopy to investigate disease-specific protein signatures holds great promise to improve our understanding of these disorders. In this review, we present the currently available quantitative proteomic approaches use in neurology, gel-based, stable isotope-labelling and label-free methodologies and evaluate their strengths and limitations. We also reported on enrichment/subfractionation methods that target the cytoskeleton associated proteins and discuss the need of alternative methods for further characterization of the neurocytoskeletal proteome. Finally, we present live cell imaging approaches and emerging dynamic microscopy technology that will provide the tools necessary to investigate protein interactions and their dynamics in the whole cells. While these areas of research are still in their infancy, they offer huge potential towards the understanding of the neuronal network stability and its modification across neuropsychiatric disorders.

The regulation of cytoskeletal and liver-specific gene expression during liver regeneration and primary hepatocyte culture

International Nuclear Information System (INIS)

Robinson, G.S.

1989-01-01

The focus of this dissertation is to determine what role(s) the extracellular matrix and expression of certain cytoskeletal genes play in the regulation of hepatocyte growth and the maintenance of a differential state. The expression of several cytoskeletal and liver-specific genes was examined during liver regeneration and in hepatocyte cultures maintained in a hormonally-defined, serum-free medium and plated on two different matrices: rat tail collagen and the EHS matrix. During liver regeneration and in hepatocytes cultured on rat tail collagen, there was a dramatic increase in tubulin mRNA levels coincident with but not linked to DNA synthesis. The message levels for other cytoskeletal genes similarly increased, while a decrease was observed in the mRNA levels of the liver-specific genes, serum albumin and alpha 1 inhibitor III. Hepatocytes cultured on the EHS matrix resulted in the maintenance of low levels of cytoskeletal gene expression and high levels of liver-specific gene expression, similar to that observed in the normal liver. Results from subcellar fractionation and two-dimensional gel electrophoresis of 35 S-labelled proteins paralleled the results seen at the mRNA level. Preliminary work suggests that microtubule organization may play a role in the expression of the liver-specific genes which encode secreted proteins. These studies, which compare hepatocytes cultured on collagen or the EHS matrix gel, reveal that both cell-cell and cell-matrix interactions play a major role in the maintenance of the differential phenotype in hepatocytes

MODELING OF DYNAMIC SYSTEMS WITH MODULATION BY MEANS OF KRONECKER VECTOR-MATRIX REPRESENTATION

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A. S. Vasilyev

2015-09-01

Full Text Available The paper deals with modeling of dynamic systems with modulation by the possibilities of state-space method. This method, being the basis of modern control theory, is based on the possibilities of vector-matrix formalism of linear algebra and helps to solve various problems of technical control of continuous and discrete nature invariant with respect to the dimension of their “input-output” objects. Unfortunately, it turned its back on the wide group of control systems, which hardware environment modulates signals. The marked system deficiency is partially offset by this paper, which proposes Kronecker vector-matrix representations for purposes of system representation of processes with signal modulation. The main result is vector-matrix representation of processes with modulation with no formal difference from continuous systems. It has been found that abilities of these representations could be effectively used in research of systems with modulation. Obtained model representations of processes with modulation are best adapted to the state-space method. These approaches for counting eigenvalues of Kronecker matrix summaries, that are matrix basis of model representations of processes described by Kronecker vector products, give the possibility to use modal direction in research of dynamics for systems with modulation. It is shown that the use of controllability for eigenvalues of general matrixes applied to Kronecker structures enabled to divide successfully eigenvalue spectrum into directed and not directed components. Obtained findings including design problems for models of dynamic processes with modulation based on the features of Kronecker vector and matrix structures, invariant with respect to the dimension of input-output relations, are applicable in the development of alternate current servo drives.

Modulator Dynamics Shape the Design Space for Stepwise-Elution Simulated Moving Bed Chromatographic Separations.

Science.gov (United States)

Wayne, Chris J; Velayudhan, Ajoy

2018-03-31

For proteins and other biological macromolecules, SMB chromatography is best operated non-isocratically. However, traditional modes of non-isocratic SMB operation generate significant mobile-phase modulator dynamics. The mechanisms by which these modulator dynamics affect a separation's success, and thus frame the design space, have yet to be explained quantitatively. Here, the dynamics of the modulator (e.g., salts in ion exchange and hydrophobic interaction chromatography) are explicitly accounted for. This leads to the elucidation of two new design constraints, presented as dimensionless numbers, which quantify the effects of the modulator phenomena and thus predict the success of a non-isocratic SMB separation. Consequently, these two new design constraints re-define the SMB design space. Computational and experimental studies at the boundaries of this design space corroborate the theoretical predictions. The design of efficient and robust operating conditions through use of the new design space is also demonstrated. © 2018 The Authors. Biotechnology Journal Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cytoskeletal Tropomyosin Tm5NM1 Is Required for Normal Excitation–Contraction Coupling in Skeletal Muscle

Science.gov (United States)

Vlahovich, Nicole; Kee, Anthony J.; Van der Poel, Chris; Kettle, Emma; Hernandez-Deviez, Delia; Lucas, Christine; Lynch, Gordon S.; Parton, Robert G.; Gunning, Peter W.

2009-01-01

The functional diversity of the actin microfilaments relies in part on the actin binding protein tropomyosin (Tm). The muscle-specific Tms regulate actin-myosin interactions and hence contraction. However, there is less known about the roles of the numerous cytoskeletal isoforms. We have shown previously that a cytoskeletal Tm, Tm5NM1, defines a Z-line adjacent cytoskeleton in skeletal muscle. Recently, we identified a second cytoskeletal Tm in this region, Tm4. Here we show that Tm4 and Tm5NM1 define separate actin filaments; the former associated with the terminal sarcoplasmic reticulum (SR) and other tubulovesicular structures. In skeletal muscles of Tm5NM1 knockout (KO) mice, Tm4 localization was unchanged, demonstrating the specificity of the membrane association. Tm5NM1 KO muscles exhibit potentiation of T-system depolarization and decreased force rundown with repeated T-tubule depolarizations consistent with altered T-tubule function. These results indicate that a Tm5NM1-defined actin cytoskeleton is required for the normal excitation–contraction coupling in skeletal muscle. PMID:19005216

Cytoskeletal tropomyosin Tm5NM1 is required for normal excitation-contraction coupling in skeletal muscle.

Science.gov (United States)

Vlahovich, Nicole; Kee, Anthony J; Van der Poel, Chris; Kettle, Emma; Hernandez-Deviez, Delia; Lucas, Christine; Lynch, Gordon S; Parton, Robert G; Gunning, Peter W; Hardeman, Edna C

2009-01-01

The functional diversity of the actin microfilaments relies in part on the actin binding protein tropomyosin (Tm). The muscle-specific Tms regulate actin-myosin interactions and hence contraction. However, there is less known about the roles of the numerous cytoskeletal isoforms. We have shown previously that a cytoskeletal Tm, Tm5NM1, defines a Z-line adjacent cytoskeleton in skeletal muscle. Recently, we identified a second cytoskeletal Tm in this region, Tm4. Here we show that Tm4 and Tm5NM1 define separate actin filaments; the former associated with the terminal sarcoplasmic reticulum (SR) and other tubulovesicular structures. In skeletal muscles of Tm5NM1 knockout (KO) mice, Tm4 localization was unchanged, demonstrating the specificity of the membrane association. Tm5NM1 KO muscles exhibit potentiation of T-system depolarization and decreased force rundown with repeated T-tubule depolarizations consistent with altered T-tubule function. These results indicate that a Tm5NM1-defined actin cytoskeleton is required for the normal excitation-contraction coupling in skeletal muscle.

Spiral-wave dynamics in excitable medium with excitability modulated by rectangle wave

International Nuclear Information System (INIS)

Yuan Guo-Yong

2011-01-01

We numerically study the dynamics of spiral waves in the excitable system with the excitability modulated by a rectangle wave. The tip trajectories and their variations with the modulation period T are explained by the corresponding spectrum analysis. For a large T, the external modulation leads to the occurrence of more frequency peaks and these frequencies change with the modulation period according to their specific rules, respectively. Some of the frequencies and a primary frequency f 1 determine the corresponding curvature periods, which are locked into rational multiplies of the modulation period. These frequency-locking behaviours and the limited life-span of the frequencies in their variations with the modulation period constitute many resonant entrainment bands in the T axis. In the main bands, which follow the relation T/T 12 = m/n, the size variable R x of the tip trajectory is a monotonic increasing function of T. The rest of the frequencies are linear combinations of the two ones. Due to the complex dynamics, many unique tip trajectories appear at some certain T. We find also that spiral waves are eliminated when T is chosen from the end of the main resonant bands. This offers a useful method of controling the spiral wave. (general)

Exploring Protein Structure and Dynamics through a Project-Oriented Biochemistry Laboratory Module

Science.gov (United States)

Lipchock, James M.; Ginther, Patrick S.; Douglas, Bonnie B.; Bird, Kelly E.; Loria, J. Patrick

2017-01-01

Here, we present a 10-week project-oriented laboratory module designed to provide a course-based undergraduate research experience in biochemistry that emphasizes the importance of biomolecular structure and dynamics in enzyme function. This module explores the impact of mutagenesis on an important active site loop for a biomedically-relevant…

Modulation of phosducin-like protein 3 (PhLP3 levels promotes cytoskeletal remodelling in a MAPK and RhoA-dependent manner.

Directory of Open Access Journals (Sweden)

Nandini V L Hayes

Full Text Available Phosducin-like protein 3 (PhLP3 forms a ternary complex with the ATP-dependent molecular chaperone CCT and its folding client tubulin. In vitro studies suggest PhLP3 plays an inhibitory role in β-tubulin folding while conversely in vivo genetic studies suggest PhLP3 is required for the correct folding of β-tubulin. We have a particular interest in the cytoskeleton, its chaperones and their role in determining cellular phenotypes associated with high level recombinant protein expression from mammalian cell expression systems.As studies into PhLP3 function have been largely carried out in non mammalian systems, we examined the effect of human PhLP3 over-expression and siRNA silencing using a single murine siRNA on both tubulin and actin systems in mammalian Chinese hamster ovary (CHO cell lines. We show that over-expression of PhLP3 promotes an imbalance of α and β tubulin subunits, microtubule disassembly and cell death. In contrast, β-actin levels are not obviously perturbed. On-the-other-hand, RNA silencing of PhLP3 increases RhoA-dependent actin filament formation and focal adhesion formation and promotes a dramatic elongated fibroblast-like change in morphology. This was accompanied by an increase in phosphorylated MAPK which has been associated with promoting focal adhesion assembly and maturation. Transient overexpression of PhLP3 in knockdown experiments rescues cells from the morphological change observed during PhLP3 silencing but mitosis is perturbed, probably reflecting a tipping back of the balance of PhLP3 levels towards the overexpression state.Our results support the hypothesis that PhLP3 is important for the maintenance of β-tubulin levels in mammalian cells but also that its modulation can promote actin-based cytoskeletal remodelling by a mechanism linked with MAPK phosphorylation and RhoA-dependent changes. PhLP3 levels in mammalian cells are thus finely poised and represents a novel target for engineering industrially

Cadmium-induced glutathionylation of actin occurs through a ROS-independent mechanism: Implications for cytoskeletal integrity

Energy Technology Data Exchange (ETDEWEB)

Choong, Grace; Liu, Ying; Xiao, Weiqun; Templeton, Douglas M., E-mail: doug.templeton@utoronto.ca

2013-10-15

Cadmium disrupts the actin cytoskeleton in rat mesangial cells, and we have previously shown that this involves a complex interplay involving activation of kinase signaling, protein translocation, and disruption of focal adhesions. Here we investigate the role that glutathionylation of actin plays in Cd{sup 2+}-associated cytoskeletal reorganization. Low concentrations of Cd{sup 2+} (0.5–2 μM) caused an increase in actin glutathionylation by 6 h, whereas at higher concentrations glutathionylation remained at basal levels. Although oxidation with diamide increased glutathionylation, reactive oxygen species (ROS) were not involved in the Cd{sup 2+}-dependent effect, as only Cd{sup 2+} concentrations above 2 μM were sufficient to increase ROS. However, low [Cd{sup 2+}] increased total glutathione levels without affecting the ratio of reduced/oxidized glutathione, and inhibition of glutathione synthesis suppressed actin glutathionylation. Cadmium increased the activity of the enzyme glutaredoxin, which influences the equilibrium between glutathionylated and deglutathionylated proteins and thus may influence levels of glutathionylated actin. Together these observations show that cadmium-dependent effects on actin glutathionylation are affected by glutathione metabolism and not by direct effects of ROS on thiol chemistry. In vitro polymerization assays with glutathionylated actin show a decreased rate of polymerization. In contrast, immunofluorescence of cytoskeletal structure in intact cells suggests that increases in actin glutathionylation accompanying increased glutathione levels occurring under low Cd{sup 2+} exposure are protective in vivo, with cytoskeletal disruption ensuing only when higher Cd{sup 2+} concentrations increase ROS levels and prevent an increase in actin–glutathione conjugates. - Highlights: • Cadmium disrupts the actin cytoskeleton in mesangial cells. • Cadmium induces glutathionylation of actin at low concentrations. �

Cadmium-induced glutathionylation of actin occurs through a ROS-independent mechanism: Implications for cytoskeletal integrity

International Nuclear Information System (INIS)

Choong, Grace; Liu, Ying; Xiao, Weiqun; Templeton, Douglas M.

2013-01-01

Cadmium disrupts the actin cytoskeleton in rat mesangial cells, and we have previously shown that this involves a complex interplay involving activation of kinase signaling, protein translocation, and disruption of focal adhesions. Here we investigate the role that glutathionylation of actin plays in Cd 2+ -associated cytoskeletal reorganization. Low concentrations of Cd 2+ (0.5–2 μM) caused an increase in actin glutathionylation by 6 h, whereas at higher concentrations glutathionylation remained at basal levels. Although oxidation with diamide increased glutathionylation, reactive oxygen species (ROS) were not involved in the Cd 2+ -dependent effect, as only Cd 2+ concentrations above 2 μM were sufficient to increase ROS. However, low [Cd 2+ ] increased total glutathione levels without affecting the ratio of reduced/oxidized glutathione, and inhibition of glutathione synthesis suppressed actin glutathionylation. Cadmium increased the activity of the enzyme glutaredoxin, which influences the equilibrium between glutathionylated and deglutathionylated proteins and thus may influence levels of glutathionylated actin. Together these observations show that cadmium-dependent effects on actin glutathionylation are affected by glutathione metabolism and not by direct effects of ROS on thiol chemistry. In vitro polymerization assays with glutathionylated actin show a decreased rate of polymerization. In contrast, immunofluorescence of cytoskeletal structure in intact cells suggests that increases in actin glutathionylation accompanying increased glutathione levels occurring under low Cd 2+ exposure are protective in vivo, with cytoskeletal disruption ensuing only when higher Cd 2+ concentrations increase ROS levels and prevent an increase in actin–glutathione conjugates. - Highlights: • Cadmium disrupts the actin cytoskeleton in mesangial cells. • Cadmium induces glutathionylation of actin at low concentrations. • Glutathionylation requires glutathione

Selective ablation of the androgen receptor in mouse sertoli cells affects sertoli cell maturation, barrier formation and cytoskeletal development.

Directory of Open Access Journals (Sweden)

Ariane Willems

2010-11-01

Full Text Available The observation that mice with a selective ablation of the androgen receptor (AR in Sertoli cells (SC (SCARKO mice display a complete block in meiosis supports the contention that SC play a pivotal role in the control of germ cell development by androgens. To delineate the physiological and molecular mechanism responsible for this control, we compared tubular development in pubertal SCARKO mice and littermate controls. Particular attention was paid to differences in SC maturation, SC barrier formation and cytoskeletal organization and to the molecular mediators potentially involved. Functional analysis of SC barrier development by hypertonic perfusion and lanthanum permeation techniques and immunohistochemical analysis of junction formation showed that SCARKO mice still attempt to produce a barrier separating basal and adluminal compartment but that barrier formation is delayed and defective. Defective barrier formation was accompanied by disturbances in SC nuclear maturation (immature shape, absence of prominent, tripartite nucleoli and SC polarization (aberrant positioning of SC nuclei and cytoskeletal elements such as vimentin. Quantitative RT-PCR was used to study the transcript levels of genes potentially related to the described phenomena between day 8 and 35. Differences in the expression of SC genes known to play a role in junction formation could be shown from day 8 for Cldn11, from day 15 for Cldn3 and Espn, from day 20 for Cdh2 and Jam3 and from day 35 for ZO-1. Marked differences were also noted in the transcript levels of several genes that are also related to cell adhesion and cytoskeletal dynamics but that have not yet been studied in SC (Actn3, Ank3, Anxa9, Scin, Emb, Mpzl2. It is concluded that absence of a functional AR in SC impedes the remodeling of testicular tubules expected at the onset of spermatogenesis and interferes with the creation of the specific environment needed for germ cell development.

Hierarchical classification of dynamically varying radar pulse repetition interval modulation patterns.

Science.gov (United States)

Kauppi, Jukka-Pekka; Martikainen, Kalle; Ruotsalainen, Ulla

2010-12-01

The central purpose of passive signal intercept receivers is to perform automatic categorization of unknown radar signals. Currently, there is an urgent need to develop intelligent classification algorithms for these devices due to emerging complexity of radar waveforms. Especially multifunction radars (MFRs) capable of performing several simultaneous tasks by utilizing complex, dynamically varying scheduled waveforms are a major challenge for automatic pattern classification systems. To assist recognition of complex radar emissions in modern intercept receivers, we have developed a novel method to recognize dynamically varying pulse repetition interval (PRI) modulation patterns emitted by MFRs. We use robust feature extraction and classifier design techniques to assist recognition in unpredictable real-world signal environments. We classify received pulse trains hierarchically which allows unambiguous detection of the subpatterns using a sliding window. Accuracy, robustness and reliability of the technique are demonstrated with extensive simulations using both static and dynamically varying PRI modulation patterns. Copyright © 2010 Elsevier Ltd. All rights reserved.

The phosphorylation status and cytoskeletal remodeling of striatal astrocytes treated with quinolinic acid

International Nuclear Information System (INIS)

Pierozan, Paula; Ferreira, Fernanda; Ortiz de Lima, Bárbara; Gonçalves Fernandes, Carolina; Totarelli Monteforte, Priscila; Castro Medaglia, Natalia de; Bincoletto, Claudia; Soubhi Smaili, Soraya; Pessoa-Pureur, Regina

2014-01-01

Quinolinic acid (QUIN) is a glutamate agonist which markedly enhances the vulnerability of neural cells to excitotoxicity. QUIN is produced from the amino acid tryptophan through the kynurenine pathway (KP). Dysregulation of this pathway is associated with neurodegenerative conditions. In this study we treated striatal astrocytes in culture with QUIN and assayed the endogenous phosphorylating system associated with glial fibrillary acidic protein (GFAP) and vimentin as well as cytoskeletal remodeling. After 24 h incubation with 100 µM QUIN, cells were exposed to 32 P-orthophosphate and/or protein kinase A (PKA), protein kinase dependent of Ca 2+ /calmodulin II (PKCaMII) or protein kinase C (PKC) inhibitors, H89 (20 μM), KN93 (10 μM) and staurosporin (10 nM), respectively. Results showed that hyperphosphorylation was abrogated by PKA and PKC inhibitors but not by the PKCaMII inhibitor. The specific antagonists to ionotropic NMDA and non-NMDA (50 µM DL-AP5 and CNQX, respectively) glutamate receptors as well as to metabotropic glutamate receptor (mGLUR; 50 µM MCPG), mGLUR1 (100 µM MPEP) and mGLUR5 (10 µM 4C3HPG) prevented the hyperphosphorylation provoked by QUIN. Also, intra and extracellular Ca 2+ quelators (1 mM EGTA; 10 µM BAPTA-AM, respectively) prevented QUIN-mediated effect, while Ca 2+ influx through voltage-dependent Ca 2+ channel type L (L-VDCC) (blocker: 10 µM verapamil) is not implicated in this effect. Morphological analysis showed dramatically altered actin cytoskeleton with concomitant change of morphology to fusiform and/or flattened cells with retracted cytoplasm and disruption of the GFAP meshwork, supporting misregulation of actin cytoskeleton. Both hyperphosphorylation and cytoskeletal remodeling were reversed 24 h after QUIN removal. Astrocytes are highly plastic cells and the vulnerability of astrocyte cytoskeleton may have important implications for understanding the neurotoxicity of QUIN in neurodegenerative disorders. - Highlights: �

A dynamic plasmonic manipulation technique assisted by phase modulation of an incident optical vortex beam

International Nuclear Information System (INIS)

Yuan, G H; Wang, Q; Tan, P S; Lin, J; Yuan, X-C

2012-01-01

A novel phase modulation method for dynamic manipulation of surface plasmon polaritons (SPPs) with a phase engineered optical vortex (OV) beam illuminating on nanoslits is experimentally demonstrated. Because of the unique helical phase carried by an OV beam, dynamic control of SPP multiple focusing and standing wave generation is realized by changing the OV beam’s topological charge constituent with the help of a liquid-crystal spatial light modulator. Measurement of SPP distributions with near-field scanning optical microscopy showed an excellent agreement with numerical predictions. The proposed phase modulation technique for manipulating SPPs features has seemingly dynamic and reconfigurable advantages, with profound potential for development of SPP coupling, routing, multiplexing and high-resolution imaging devices on plasmonic chips. (paper)

Ligand mobility modulates immunological synapse formation and T cell activation.

Directory of Open Access Journals (Sweden)

Chih-Jung Hsu

Full Text Available T cell receptor (TCR engagement induces clustering and recruitment to the plasma membrane of many signaling molecules, including the protein tyrosine kinase zeta-chain associated protein of 70 kDa (ZAP70 and the adaptor SH2 domain-containing leukocyte protein of 76 kDa (SLP76. This molecular rearrangement results in formation of the immunological synapse (IS, a dynamic protein array that modulates T cell activation. The current study investigates the effects of apparent long-range ligand mobility on T cell signaling activity and IS formation. We formed stimulatory lipid bilayers on glass surfaces from binary lipid mixtures with varied composition, and characterized these surfaces with respect to diffusion coefficient and fluid connectivity. Stimulatory ligands coupled to these surfaces with similar density and orientation showed differences in their ability to activate T cells. On less mobile membranes, central supramolecular activation cluster (cSMAC formation was delayed and the overall accumulation of CD3ζ at the IS was reduced. Analysis of signaling microcluster (MC dynamics showed that ZAP70 MCs exhibited faster track velocity and longer trajectories as a function of increased ligand mobility, whereas movement of SLP76 MCs was relatively insensitive to this parameter. Actin retrograde flow was observed on all surfaces, but cell spreading and subsequent cytoskeletal contraction were more pronounced on mobile membranes. Finally, increased tyrosine phosphorylation and persistent elevation of intracellular Ca(2+ were observed in cells stimulated on fluid membranes. These results point to ligand mobility as an important parameter in modulating T cell responses.

Seasonal module dynamics of Turbinaria triquetra (Fucales, Phaeophyceae) in the southern Red Sea

NARCIS (Netherlands)

Ateweberhan, Mebrahtu; Bruggemann, J. Henrich; Breeman, Anneke M.

2006-01-01

Module dynamics in the fucoid alga Turbinaria triquetra (J. Agardh) Kutzing were studied on a shallow reef flat in the southern Red Sea. Seasonal patterns in thallus density and size were determined, and the initiation, growth, reproduction, and shedding of modules were studied using a tagging

Effect of Rapid Chilling on Beef Quality and Cytoskeletal Protein Degradation in of Chinese Yellow Crossbred Bulls

Directory of Open Access Journals (Sweden)

Yanwei Mao

2012-08-01

Full Text Available The objective of this study was to investigate the effect of rapid chilling (RC on beef quality and the degradation of cytoskeletal proteins. Twenty Chinese Yellow crossbred bulls were selected and randomly divided into two groups. RC and conventional chilling (CC were applied to left and right sides of the carcasses respectively after slaughtering. To determine whether electrical stimulation (ES treatment can alleviate the potential hazard of RC on meat quality, ES was applied to one group. The effects of RC and ES were determined by meat color, shear force and cytoskeletal protein degradation postmortem (PM. The results showed that RC decreased beef tenderness at 1 d and 3 d postmortem, but had no detrimental effect on meat color. Western blotting showed that RC decreased the degradation rate of desmin and troponin-T, but the effects weakened gradually as postmortem aging extended. Degradation rates of both desmin and troponin-T were accelerated by ES. The combination of RC and ES could improve beef color, accelerate degradation rate of cytoskeletal protein and improve beef tenderness.

The ADF/Cofilin-Pathway and Actin Dynamics in Podocyte Injury

Directory of Open Access Journals (Sweden)

Beina Teng

2012-01-01

Full Text Available ADF/cofilins are the major regulators of actin dynamics in mammalian cells. The activation of ADF/cofilins is controlled by a variety of regulatory mechanisms. Dysregulation of ADF/cofilin may result in loss of a precisely organized actin cytoskeletal architecture and can reduce podocyte migration and motility. Recent studies suggest that cofilin-1 can be regulated through several extracellular signals and slit diaphragm proteins. Cofilin knockdown and knockout animal models show dysfunction of glomerular barrier and filtration with foot process effacement and loss of secondary foot processes. This indicates that cofilin-1 is necessary for modulating actin dynamics in podocytes. Podocyte alterations in actin architecture may initiate or aid the progression of a large variety of glomerular diseases, and cofilin activity is required for reorganization of an intact filtration barrier. Since almost all proteinuric diseases result from a similar phenotype with effacement of the foot processes, we propose that cofilin-1 is at the centre stage of the development of proteinuria and thus may be an attractive drug target for antiproteinuric treatment strategies.

Self-modulated dynamics of a relativistic charged particle beam in plasma wake field excitation

Energy Technology Data Exchange (ETDEWEB)

Akhter, T.; Fedele, R. [Dipartimento di Fisica ‘Ettore Pancini’, Università di Napoli Federico II and INFN Sezione di Napoli, Napoli (Italy); Nicola, S. De [CNR-SPIN and INFN Sezione di Napoli, Napoli (Italy); Tanjia, F. [Dipartimento di Fisica ‘Ettore Pancini’, Università di Napoli Federico II and INFN Sezione di Napoli, Napoli (Italy); Jovanović, D. [Institute of Physics, University of Belgrade, Belgrade (Serbia); Mannan, A. [Department of Physics, Jahangirnagar University, Savar, Dhaka (Bangladesh)

2016-09-01

The self-modulated dynamics of a relativistic charged particle beam is provided within the context of the theory of plasma wake field excitation. The self-consistent description of the beam dynamics is provided by coupling the Vlasov equation with a Poisson-type equation relating the plasma wake potential to the beam density. An analysis of the beam envelope self-modulation is then carried out and the criteria for the occurrence of the instability are discussed thereby.

Reorganization of the actin cytoskeleton via transcriptional regulation of cytoskeletal/focal adhesion genes by myocardin-related transcription factors (MRTFs/MAL/MKLs)

International Nuclear Information System (INIS)

Morita, Tsuyoshi; Mayanagi, Taira; Sobue, Kenji

2007-01-01

RhoA is a crucial regulator of stress fiber and focal adhesion formation through the activation of actin nucleation and polymerization. It also regulates the nuclear translocation of myocardin-related transcription factor-A and -B (MRTF-A/B, MAL or MKL 1/2), which are co-activators of serum response factor (SRF). In dominant-negative MRTF-A (DN-MRTF-A)-expressing NIH 3T3 cell lines, the expressions of several cytoskeletal/focal adhesion genes were down-regulated, and the formation of stress fiber and focal adhesion was severely diminished. MRTF-A/B-knockdown cells also exhibited such cytoskeletal defects. In reporter assays, both RhoA and MRTF-A enhanced promoter activities of these genes in a CArG-box-dependent manner, and DN-MRTF-A inhibited the RhoA-mediated activation of these promoters. In dominant-negative RhoA (RhoA-N19)-expressing NIH 3T3 cell lines, the nuclear translocation of MRTF-A/B was predominantly prevented, resulting in the reduced expression of cytoskeletal/focal adhesion proteins. Further, constitutive-active MRTF-A/B increased the expression of endogenous cytoskeletal/focal adhesion proteins, and thereby rescued the defective phenotype of stress fibers and focal adhesions in RhoA-N19 expressing cells. These results indicate that MRTF-A/B act as pivotal mediators of stress fiber and focal adhesion formation via the transcriptional regulation of a subset of cytoskeletal/focal adhesion genes

Thermal Equilibrium Dynamic Control Based on DPWM Dual-Mode Modulation of High Power NPC Three-Level Inverter

Directory of Open Access Journals (Sweden)

Shi-Zhou Xu

2016-01-01

Full Text Available In some special applications of NPC three-level inverters, such as mine hoist, there exist special conditions of overloading during the whole hoisting process and large overload in starting stage, during which the power-loss calculation of power devices and thermal control are important factors affecting the thermal stability of inverters. The principles of SVPWM and DPWM were described in this paper firstly, based on which the dynamic power losses of the two modulations of hoist in single period were calculated. Secondly, a thermal equilibrium dynamic control based on DPMW dual-mode modulation was proposed, which can switch the modulation dynamically according to the change of dynamic power loss to realize dynamic control of power loss and thermal equilibrium of inverter. Finally, simulation and experiment prove the effectiveness of the proposed strategy.

A Multi-Cycle Q-Modulation for Dynamic Optimization of Inductive Links.

Science.gov (United States)

Lee, Byunghun; Yeon, Pyungwoo; Ghovanloo, Maysam

2016-08-01

This paper presents a new method, called multi-cycle Q-modulation, which can be used in wireless power transmission (WPT) to modulate the quality factor (Q) of the receiver (Rx) coil and dynamically optimize the load impedance to maximize the power transfer efficiency (PTE) in two-coil links. A key advantage of the proposed method is that it can be easily implemented using off-the-shelf components without requiring fast switching at or above the carrier frequency, which is more suitable for integrated circuit design. Moreover, the proposed technique does not need any sophisticated synchronization between the power carrier and Q-modulation switching pulses. The multi-cycle Q-modulation is analyzed theoretically by a lumped circuit model, and verified in simulation and measurement using an off-the-shelf prototype. Automatic resonance tuning (ART) in the Rx, combined with multi-cycle Q-modulation helped maximizing PTE of the inductive link dynamically in the presence of environmental and loading variations, which can otherwise significantly degrade the PTE in multi-coil settings. In the prototype conventional 2-coil link, the proposed method increased the power amplifier (PA) plus inductive link efficiency from 4.8% to 16.5% at ( R L = 1 kΩ, d 23 = 3 cm), and from 23% to 28.2% at ( R L = 100 Ω, d 23 = 3 cm) after 11% change in the resonance capacitance, while delivering 168.1 mW to the load (PDL).

Expression analysis of cellulose synthase and main cytoskeletal protein genes in flax (Linum usitatissimum L.).

Science.gov (United States)

Galinousky, Dmitry; Padvitski, Tsimafei; Bayer, Galina; Pirko, Yaroslav; Pydiura, Nikolay; Anisimova, Natallia; Nikitinskaya, Tatyana; Khotyleva, Liubov; Yemets, Alla; Kilchevsky, Aleksandr; Blume, Yaroslav

2017-08-09

Fiber flax is an important source of natural fiber and a comprehensive model for the plant fiber biogenesis studies. Cellulose-synthase (CesA) and cytoskeletal genes are known to be important for the cell wall biogenesis in general and for the biogenesis of flax fibers in particular. Currently, knowledge about activity of these genes during the plant growth is limited. In this study, we have investigated flax fiber biogenesis by measuring expression of CesA and cytoskeletal genes at two stages of the flax development (seedlings and stems at the rapid growth stage) in several flax subspecies (elongatum, mediterraneum, crepitans). RT-qPCR has been used to quantify the expression of LusСesA1, LusСesA4, LusСesA7, LusСesA6, Actin, and α-Tubulin genes in plant samples. We report that CesA genes responsible for the secondary cell wall synthesis (LusCesA4, LusCesA7) have different expression pattern compared with CesA genes responsible for the primary cell wall synthesis (LusCesA1, LusCesA6): an average expression of LusCesA4 and LusCesA7 genes is relatively high in seedlings and further increases in stems at the rapid growth stage, whereas an average expression of LusCesA1 and LusCesA6 genes decreases. Interestingly, LusCesA1 is the only studied gene with different expression dynamics between the flax subspecies: its expression decreases by 5.2-10.7 folds in elongatum and mediterraneum but does not change in crepitans subspecies when the rapid growth stage and seedlings are compared. The expression of cytoskeleton genes (coding actin and α-tubulin) is relatively stable and significantly higher than the expression of cellulose-synthase genes in all the studied samples. © 2017 International Federation for Cell Biology.

Predicting the effects of organ motion on the dose delivered by dynamic intensity modulation

International Nuclear Information System (INIS)

Yu, C.X.; Jaffray, David; Martinez, A.A.; Wong, J.W.

1997-01-01

Purpose: Computer-optimized treatment plans, aimed to enhance tumor control and reduce normal tissue complication, generally require non-uniform beam intensities. One of the techniques for delivering intensity-modulated beams is the use of dynamic multileaf collimation, where the beam aperture and field shape change during irradiation. When intensity-modulated beams are delivered with dynamic collimation, intra-treatment organ motion may not only cause geometric misses at the field boundaries but also create hot and cold spots in the target. The mechanism for producing such effects has not been well understood. This study analyzes the dosimetric effects of intra-treatment organ motion on dynamic intensity modulation. A numerical method is developed for predicting the intensity distributions in a moving target before dose is delivered with dynamic intensity modulation. Material and Methods: In the numerical algorithm, the change in position and shape of the beam aperture with time were modeled as a three-dimensional 'tunnel', with the shape of the field aperture described in the x-y plane and its temporal position shown in the z-dimension. A point in the target had to be in the tunnel in order to receive irradiation and the dose to the point was proportional to the amount of time that this point stayed in the tunnel. Since each point in the target were analyzed separately, non-rigid body variations could easily be handled. The dependency of the dose variations on all parameters involved, including the speed of collimator motion, the frequency and amplitude of the target motion, and the size of the field segments, was analyzed. The algorithm was verified by irradiating moving phantoms with beams of dynamically modulated intensities. Predictions were also made for a treatment of a thoracic tumor using a dynamic wedge. The changes of target position with time were based on the MRI images of the chest region acquired using fast MRI scans in a cine fashion for a duration

The autonomic higher order processing nuclei of the lower brain stem are among the early targets of the Alzheimer's disease-related cytoskeletal pathology.

Science.gov (United States)

Rüb, U; Del Tredici, K; Schultz, C; Thal, D R; Braak, E; Braak, H

2001-06-01

The nuclei of the pontine parabrachial region (medial parabrachial nucleus, MPB; lateral parabrachial nucleus, LPB; subpeduncular nucleus, SPP) together with the intermediate zone of the medullary reticular formation (IRZ) are pivotal relay stations within central autonomic regulatory feedback systems. This study was undertaken to investigate the evolution of the Alzheimer's disease-related cytoskeletal pathology in these four sites of the lower brain stem. We examined the MPB, LPB, SPP and IRZ in 27 autopsy cases and classified the cortical Alzheimer-related cytoskeletal anomalies according to an established staging system (neurofibrillary tangle/neuropil threads [NFT/NT] stages I-VI). The lesions were visualized either with the antibody AT8, which is immunospecific for the abnormally phosphorylated form of the cytoskeletal protein tau, or with a modified Gallyas silver iodide stain. The MPB, SPB, and IRZ display cytoskeletal pathology in stage I and the LPB in stage II, whereby bothstages correspond to the preclinical phase of Alzheimer's disease (AD). In stages III-IV (incipient AD), the MPB and SPP are severely affected. In all of the stage III-IV cases, the lesions in the LPB and IRZ are well developed. In stages V and VI (clinical phase of AD), the MPB and SPP are filled with the abnormal intraneuronal material. At stages V-VI, the LPB is moderately involved and the IRZ shows severe damage. The pathogenesis of the AD-related cytoskeletal lesions in the nuclei of the pontine parabrachial region and in the IRZ conforms with the cortical NFT/NT staging sequence I-VI. In the event that the cytoskeletal pathology observed in this study impairs the function of the nerve cells involved, it is conceivable that autonomic mechanisms progressively deteriorate with advancing cortical NFT/NT stages. This relationship remains to be established, but it could provide insights into the illusive correlation between the AD-related cytoskeletal pathology and the function of

Biosynthesis of intestinal microvillar proteins. Rapid expression of cytoskeletal components in microvilli of pig small intestinal mucosal explants

DEFF Research Database (Denmark)

Cowell, G M; Danielsen, E M

1984-01-01

Using alkaline extraction to separate cytoskeletal and membrane proteins of intestinal microvilli, the kinetics of assembly of these two microvillar protein compartments was studied by pulse-chase labelling of pig small intestinal mucosal explants, kept in organ culture. Following a 10 min pulse...... of [35S]methionine, the membrane proteins did not appear in the microvillar fraction until after 40-60 min of chase. In contrast, the cytoskeletal components, of which the 110-kDa protein and villin were immunologically identified, were expressed in the microvillar fraction immediately after the 10 min...

Hes6 is required for actin cytoskeletal organization in differentiating C2C12 myoblasts

Energy Technology Data Exchange (ETDEWEB)

Malone, Caroline M.P.; Domaschenz, Renae; Amagase, Yoko [MRC Cancer Cell Unit, Hutchison-MRC Research Centre, Addenbrooke' s Hospital, Cambridge CB2 0XZ (United Kingdom); Dunham, Ian [EMBL-European Bioinformatics Institute (EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD (United Kingdom); Murai, Kasumi [MRC Cancer Cell Unit, Hutchison-MRC Research Centre, Addenbrooke' s Hospital, Cambridge CB2 0XZ (United Kingdom); Jones, Philip H., E-mail: phj20@cam.ac.uk [MRC Cancer Cell Unit, Hutchison-MRC Research Centre, Addenbrooke' s Hospital, Cambridge CB2 0XZ (United Kingdom)

2011-07-01

Hes6 is a member of the hairy-enhancer-of-split family of transcription factors that regulate proliferating cell fate in development and is known to be expressed in developing muscle. Here we investigate its function in myogenesis in vitro. We show that Hes6 is a direct transcriptional target of the myogenic transcription factors MyoD and Myf5, indicating that it is integral to the myogenic transcriptional program. The localization of Hes6 protein changes during differentiation, becoming predominantly nuclear. Knockdown of Hes6 mRNA levels by siRNA has no effect on cell cycle exit or induction of myosin heavy chain expression in differentiating C2C12 myoblasts, but F-actin filament formation is disrupted and both cell motility and myoblast fusion are reduced. The knockdown phenotype is rescued by expression of Hes6 cDNA resistant to siRNA. These results define a novel role for Hes6 in actin cytoskeletal dynamics in post mitotic myoblasts.

Hes6 is required for actin cytoskeletal organization in differentiating C2C12 myoblasts

International Nuclear Information System (INIS)

Malone, Caroline M.P.; Domaschenz, Renae; Amagase, Yoko; Dunham, Ian; Murai, Kasumi; Jones, Philip H.

2011-01-01

Hes6 is a member of the hairy-enhancer-of-split family of transcription factors that regulate proliferating cell fate in development and is known to be expressed in developing muscle. Here we investigate its function in myogenesis in vitro. We show that Hes6 is a direct transcriptional target of the myogenic transcription factors MyoD and Myf5, indicating that it is integral to the myogenic transcriptional program. The localization of Hes6 protein changes during differentiation, becoming predominantly nuclear. Knockdown of Hes6 mRNA levels by siRNA has no effect on cell cycle exit or induction of myosin heavy chain expression in differentiating C2C12 myoblasts, but F-actin filament formation is disrupted and both cell motility and myoblast fusion are reduced. The knockdown phenotype is rescued by expression of Hes6 cDNA resistant to siRNA. These results define a novel role for Hes6 in actin cytoskeletal dynamics in post mitotic myoblasts.

The phosphorylation status and cytoskeletal remodeling of striatal astrocytes treated with quinolinic acid

Energy Technology Data Exchange (ETDEWEB)

Pierozan, Paula; Ferreira, Fernanda; Ortiz de Lima, Bárbara; Gonçalves Fernandes, Carolina [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003 (Brazil); Totarelli Monteforte, Priscila; Castro Medaglia, Natalia de; Bincoletto, Claudia; Soubhi Smaili, Soraya [Departamento de Farmacologia, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, SP (Brazil); Pessoa-Pureur, Regina, E-mail: rpureur@ufrgs.br [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003 (Brazil)

2014-04-01

Quinolinic acid (QUIN) is a glutamate agonist which markedly enhances the vulnerability of neural cells to excitotoxicity. QUIN is produced from the amino acid tryptophan through the kynurenine pathway (KP). Dysregulation of this pathway is associated with neurodegenerative conditions. In this study we treated striatal astrocytes in culture with QUIN and assayed the endogenous phosphorylating system associated with glial fibrillary acidic protein (GFAP) and vimentin as well as cytoskeletal remodeling. After 24 h incubation with 100 µM QUIN, cells were exposed to {sup 32}P-orthophosphate and/or protein kinase A (PKA), protein kinase dependent of Ca{sup 2+}/calmodulin II (PKCaMII) or protein kinase C (PKC) inhibitors, H89 (20 μM), KN93 (10 μM) and staurosporin (10 nM), respectively. Results showed that hyperphosphorylation was abrogated by PKA and PKC inhibitors but not by the PKCaMII inhibitor. The specific antagonists to ionotropic NMDA and non-NMDA (50 µM DL-AP5 and CNQX, respectively) glutamate receptors as well as to metabotropic glutamate receptor (mGLUR; 50 µM MCPG), mGLUR1 (100 µM MPEP) and mGLUR5 (10 µM 4C3HPG) prevented the hyperphosphorylation provoked by QUIN. Also, intra and extracellular Ca{sup 2+} quelators (1 mM EGTA; 10 µM BAPTA-AM, respectively) prevented QUIN-mediated effect, while Ca{sup 2+} influx through voltage-dependent Ca{sup 2+} channel type L (L-VDCC) (blocker: 10 µM verapamil) is not implicated in this effect. Morphological analysis showed dramatically altered actin cytoskeleton with concomitant change of morphology to fusiform and/or flattened cells with retracted cytoplasm and disruption of the GFAP meshwork, supporting misregulation of actin cytoskeleton. Both hyperphosphorylation and cytoskeletal remodeling were reversed 24 h after QUIN removal. Astrocytes are highly plastic cells and the vulnerability of astrocyte cytoskeleton may have important implications for understanding the neurotoxicity of QUIN in neurodegenerative

Cytoskeletal proteins in the cerebrospinal fluid as biomarker of multiple sclerosis.

Science.gov (United States)

Madeddu, Roberto; Farace, Cristiano; Tolu, Paola; Solinas, Giuliana; Asara, Yolande; Sotgiu, Maria Alessandra; Delogu, Lucia Gemma; Prados, Jose Carlos; Sotgiu, Stefano; Montella, Andrea

2013-02-01

The axonal cytoskeleton is a finely organized system, essential for maintaining the integrity of the axon. Axonal degeneration is implicated in the pathogenesis of unremitting disability of multiple sclerosis (MS). Purpose of this study is to evaluate levels of cytoskeletal proteins such as neurofilament light protein (NFL), glial fibrillary acidic protein (GFAP), and β-tubulin (β-Tub) isoforms II and III in the cerebrospinal fluid (CSF) of MS patients and their correlation with MS clinical indices. CSF levels of cytoskeletal proteins were determined in 51 patients: 33 with MS and 18 with other neurological diseases (OND). NFL, GFAP and β-Tub II proteins were significantly higher (p 0.05) was found between MS and OND with regard to β-Tub III. Interestingly, levels of β-Tub III and NFL were higher in progressive than in remitting MS forms; on the contrary, higher levels of β-Tub II and GFAP were found in remitting MS forms. However, with the exception of β-Tub III, all proteins tend to decrease their CSF levels concomitantly with the increasing disability (EDSS) score. Overall, our results might indicate β-Tub II as a potential candidate for diagnostic and β-Tub III as a possible prognostic biomarker of MS. Therefore, further analyses are legitimated and desirable.

Cholera toxin can catalyze ADP-ribosylation of cytoskeletal proteins

International Nuclear Information System (INIS)

Kaslow, H.R.; Groppi, V.E.; Abood, M.E.; Bourne, H.R.

1981-01-01

Cholera toxin catalyzes transfer of radiolabel from [ 32 P]NAD + to several peptides in particulate preparations of human foreskin fibroblasts. Resolution of these peptides by two-dimensional gel electrophoresis allowed identification of two peptides of M/sub r/ = 42,000 and 52,000 as peptide subunits of a regulatory component of adenylate cyclase. The radiolabeling of another group of peptides (M/sub r/ = 50,000 to 65,000) suggested that cholera toxin could catalyze ADP-ribosylation of cytoskeletal proteins. This suggestion was confirmed by showing that incubation with cholera toxin and [ 32 P]NAD + caused radiolabeling of purified microtubule and intermediate filament proteins

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

Science.gov (United States)

Appert-Rolland, C.; Ebbinghaus, M.; Santen, L.

2015-09-01

Cells are the elementary units of living organisms, which are able to carry out many vital functions. These functions rely on active processes on a microscopic scale. Therefore, they are strongly out-of-equilibrium systems, which are driven by continuous energy supply. The tasks that have to be performed in order to maintain the cell alive require transportation of various ingredients, some being small, others being large. Intracellular transport processes are able to induce concentration gradients and to carry objects to specific targets. These processes cannot be carried out only by diffusion, as cells may be crowded, and quite elongated on molecular scales. Therefore active transport has to be organized. The cytoskeleton, which is composed of three types of filaments (microtubules, actin and intermediate filaments), determines the shape of the cell, and plays a role in cell motion. It also serves as a road network for a special kind of vehicles, namely the cytoskeletal motors. These molecules can attach to a cytoskeletal filament, perform directed motion, possibly carrying along some cargo, and then detach. It is a central issue to understand how intracellular transport driven by molecular motors is regulated. The interest for this type of question was enhanced when it was discovered that intracellular transport breakdown is one of the signatures of some neuronal diseases like the Alzheimer. We give a survey of the current knowledge on microtubule based intracellular transport. Our review includes on the one hand an overview of biological facts, obtained from experiments, and on the other hand a presentation of some modeling attempts based on cellular automata. We present some background knowledge on the original and variants of the TASEP (Totally Asymmetric Simple Exclusion Process), before turning to more application oriented models. After addressing microtubule based transport in general, with a focus on in vitro experiments, and on cooperative effects in the

Dynamic excitatory and inhibitory gain modulation can produce flexible, robust and optimal decision-making.

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Ritwik K Niyogi

Full Text Available Behavioural and neurophysiological studies in primates have increasingly shown the involvement of urgency signals during the temporal integration of sensory evidence in perceptual decision-making. Neuronal correlates of such signals have been found in the parietal cortex, and in separate studies, demonstrated attention-induced gain modulation of both excitatory and inhibitory neurons. Although previous computational models of decision-making have incorporated gain modulation, their abstract forms do not permit an understanding of the contribution of inhibitory gain modulation. Thus, the effects of co-modulating both excitatory and inhibitory neuronal gains on decision-making dynamics and behavioural performance remain unclear. In this work, we incorporate time-dependent co-modulation of the gains of both excitatory and inhibitory neurons into our previous biologically based decision circuit model. We base our computational study in the context of two classic motion-discrimination tasks performed in animals. Our model shows that by simultaneously increasing the gains of both excitatory and inhibitory neurons, a variety of the observed dynamic neuronal firing activities can be replicated. In particular, the model can exhibit winner-take-all decision-making behaviour with higher firing rates and within a significantly more robust model parameter range. It also exhibits short-tailed reaction time distributions even when operating near a dynamical bifurcation point. The model further shows that neuronal gain modulation can compensate for weaker recurrent excitation in a decision neural circuit, and support decision formation and storage. Higher neuronal gain is also suggested in the more cognitively demanding reaction time than in the fixed delay version of the task. Using the exact temporal delays from the animal experiments, fast recruitment of gain co-modulation is shown to maximize reward rate, with a timescale that is surprisingly near the

Dynamic nuclear polarization using frequency modulation at 3.34 T.

Science.gov (United States)

Hovav, Y; Feintuch, A; Vega, S; Goldfarb, D

2014-01-01

During dynamic nuclear polarization (DNP) experiments polarization is transferred from unpaired electrons to their neighboring nuclear spins, resulting in dramatic enhancement of the NMR signals. While in most cases this is achieved by continuous wave (cw) irradiation applied to samples in fixed external magnetic fields, here we show that DNP enhancement of static samples can improve by modulating the microwave (MW) frequency at a constant field of 3.34 T. The efficiency of triangular shaped modulation is explored by monitoring the (1)H signal enhancement in frozen solutions containing different TEMPOL radical concentrations at different temperatures. The optimal modulation parameters are examined experimentally and under the most favorable conditions a threefold enhancement is obtained with respect to constant frequency DNP in samples with low radical concentrations. The results are interpreted using numerical simulations on small spin systems. In particular, it is shown experimentally and explained theoretically that: (i) The optimal modulation frequency is higher than the electron spin-lattice relaxation rate. (ii) The optimal modulation amplitude must be smaller than the nuclear Larmor frequency and the EPR line-width, as expected. (iii) The MW frequencies corresponding to the enhancement maxima and minima are shifted away from one another when using frequency modulation, relative to the constant frequency experiments. Copyright © 2013 Elsevier Inc. All rights reserved.

Dynamics of simple magnetorheological suspensions under rotating magnetic fields with modulated Mason number

International Nuclear Information System (INIS)

Calderon, Oscar G; Melle, Sonia

2002-01-01

We study theoretically the dynamics of a system of two magnetizable particles suspended in a non-magnetic fluid subject to a rotating magnetic field when a modulation on the Mason number (ratio of viscous to magnetic forces) is applied. We find, using a periodic modulation, that a resonant-like phenomenon between the periodic modulation of the Mason number and the intrinsic radial oscillation of the system without modulation occurs. For a random perturbation of the Mason number, we obtain an optimum noise strength at which the average interparticle distance reaches the lowest value. When a weak periodic modulation and a noise source are included in the Mason number, stochastic resonance (SR) is found for different frequencies and amplitudes of the modulation. An interpretation of this SR phenomenon is made by means of a threshold crossing mechanism

Dynamic regime of coherent population trapping and optimization of frequency modulation parameters in atomic clocks.

Science.gov (United States)

Yudin, V I; Taichenachev, A V; Basalaev, M Yu; Kovalenko, D V

2017-02-06

We theoretically investigate the dynamic regime of coherent population trapping (CPT) in the presence of frequency modulation (FM). We have formulated the criteria for quasi-stationary (adiabatic) and dynamic (non-adiabatic) responses of atomic system driven by this FM. Using the density matrix formalism for Λ system, the error signal is exactly calculated and optimized. It is shown that the optimal FM parameters correspond to the dynamic regime of atomic-field interaction, which significantly differs from conventional description of CPT resonances in the frame of quasi-stationary approach (under small modulation frequency). Obtained theoretical results are in good qualitative agreement with different experiments. Also we have found CPT-analogue of Pound-Driver-Hall regime of frequency stabilization.

Using Force to Probe Single-Molecule Receptor-Cytoskeletal Anchoring Beneath the Surface of a Living Cell

DEFF Research Database (Denmark)

Evans, Evan; Kinoshita, Koji

2007-01-01

-cytoskeletal unbinding increased exponentially with the level of force, suggesting disruption at a site of single-molecule interaction. Since many important enzymes and signaling molecules are closely associated with a membrane receptor-cytoskeletal linkage, pulling on a receptor could alter interactions among its......The ligation of cell surface receptors often communicates a signal that initiates a cytoplasmic chemical cascade to implement an important cell function. Less well understood is how physical stress applied to a cell surface adhesive bond propagates throughout the cytostructure to catalyze...... or trigger important steps in these chemical processes. Probing the nanoscale impact of pulling on cell surface bonds, we discovered that receptors frequently detach prematurely from the interior cytostructure prior to failure of the exterior adhesive bond [Evans, E., Heinrich, V., Leung, A., and Kinoshita...

Solar dynamic power module design

Science.gov (United States)

Secunde, Richard R.; Labus, Thomas L.; Lovely, Ronald G.

1989-01-01

Studies have shown that the use of solar dynamic (SD) power for the growth areas of the Space Station Freedom program will result in life cycle cost savings when compared to power supplied by photovoltaic sources. In the SD power module, a concentrator collects and focuses solar energy into a heat receiver which has integral thermal energy storage. A Power Conversion Unit (PCU) based on the closed Brayton cycle removes thermal energy from the receiver and converts that energy to electrical energy. Since the closed Brayton cycle is a single phase gas cycle, the conversion hardware (heat exchangers, turbine, compressor, etc.) can be designed for operation in low earth orbit, and tested with confidence in test facilities on earth before launch into space. The concentrator subassemblies will be aligned and the receiver/PCU/radiator combination completely assembled and charged with gas and cooling liquid on earth before launch to, and assembly on, orbit.

Mertk deficiency affects macrophage directional migration via disruption of cytoskeletal organization.

Directory of Open Access Journals (Sweden)

Yong Tang

Full Text Available Mertk belongs to the Tyro3, Axl and Mertk (TAM family of receptor tyrosine kinases, and plays a pivotal role in regulation of cytoskeletal rearrangement during phagocytosis. Phagocytosis by either professional or non-professional phagocytes is impaired in the Mertk deficient individual. In the present study, we further investigated the effects of Mertk mutation on peritoneal macrophage morphology, attachment, spreading and movement. Mertk-mutated macrophages exhibited decreased attachment, weak spreading, loss of spindle-like body shape and lack of clear leading and trailing edges within the first few hours of culture, as observed by environmental scanning electron microscopy. Time-lapse video photography recording showed that macrophage without Mertk conducted mainly random movement with oscillating swing around the cell body, and lost the directional migration action seen on the WT cells. Western blotting showed a decreased phosphorylation of focal adhesion kinase (FAK. Immunocytochemistry revealed that actin filaments and dynamic protein myosin II failed to concentrate in the leading edge of migrating cells. Microtubules were localized mainly in one side of mutant cell body, with no clear MTOC and associated radially-distributed microtubule bundles, which were clearly evident in the WT cells. Our results suggest that Mertk deficiency affects not only phagocytosis but also cell shape and migration, likely through a common regulatory mechanism on cytoskeletons.

Parathyroid hormone promotes the disassembly of cytoskeletal actin and myosin in cultured osteoblastic cells: Mediation by cyclic AMP

International Nuclear Information System (INIS)

Egan, J.J.; Gronowicz, G.; Rodan, G.A.

1991-01-01

Parathyroid hormone (PTH) alters the shape of osteoblastic cells both in vivo and in vitro. In this study, we examined the effect of PTH on cytoskeletal actin and myosin, estimated by polyacrylamide gel electrophoresis of Triton X-100 (1%) nonextractable proteins. After 2-5 minutes, PTH caused a rapid and transient decrease of 50-60% in polymerized actin and myosin associated with the Triton X-100 nonextractable cytoskeleton. Polymerized actin returned to control levels by 30 min. The PTH effect was dose-dependent with an IC50 of about 1 nM, and was partially inhibited by the (3-34) PTH antagonist. PTH caused a rapid transient rise in cyclic AMP (cAMP) in these cells that peaked at 4 min, while the nadir in cytoskeletal actin and myosin was recorded around 5 min. The intracellular calcium chelator Quin-2/AM (10 microM) also decreased cytoskeletal actin and myosin, to the same extent as did PTH (100 nM). To distinguish between cAMP elevation and Ca++ reduction as mediators of PTH action, we measured the phosphorylation of the 20 kD (PI 4.9) myosin light chain in cells preincubated with [32P]-orthophosphate. The phosphorylation of this protein decreased within 2-3 min after PTH addition and returned to control levels after 5 min. The calcium ionophore A-23187 did not antagonize this PTH effect. Visualization of microfilaments with rhodamine-conjugated phalloidin showed that PTH altered the cytoskeleton by decreasing the number of stress fibers. These changes in the cytoskeleton paralleled changes in the shape of the cells from a spread configuration to a stellate form with retracting processes. The above findings indicate that the alteration in osteoblast shape produced by PTH involve relatively rapid and transient changes in cytoskeletal organization that appear to be mediated by cAMP

Cytoskeletal proteins in the follicular wall of normal andcystic ovaries of sows

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Fabiano J.F. de Sant'Ana

2015-02-01

Full Text Available The expression of cytoskeletal proteins was evaluated immunohistochemically in 36 normal ovaries sampled from 18 sows and 44 cystic ovaries sampled from of 22 sows, was evaluated. All sows had history of reproductive problems, such as infertility or subfertility. The immunohistochemically stained area (IHCSA was quantified through image analysis to evaluate the expression of these proteins in the follicular wall of secondary, tertiary, and cystic follicles. Cytokeratins (CK immunoreactivity was strong in the granulosa cell layer (GC and mild in the theca interna (TI and externa (TE of the normal follicles. There was severe reduction of the reaction to CK in the GC in the cystic follicles, mainly in the luteinized cysts. The immunoreactivity for vimentin was higher in the GC from normal and cystic follicles in contrast with the other follicular structures. In the luteinized cysts, the IHCSA for vimentin was significantly higher in TI and in both observed cysts, the labeling was more accentuated in TE. Immunohistochemical detection of desmin and α-SMA was restricted to the TE, without differences between the normal and cystic follicles. The results of the current study show that the development of ovarian cysts in sows is associated to changes in the expression of the cytoskeletal proteins CK and vimentin.

Reinforcement versus fluidization in cytoskeletal mechanoresponsiveness.

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Ramaswamy Krishnan

Full Text Available Every adherent eukaryotic cell exerts appreciable traction forces upon its substrate. Moreover, every resident cell within the heart, great vessels, bladder, gut or lung routinely experiences large periodic stretches. As an acute response to such stretches the cytoskeleton can stiffen, increase traction forces and reinforce, as reported by some, or can soften and fluidize, as reported more recently by our laboratory, but in any given circumstance it remains unknown which response might prevail or why. Using a novel nanotechnology, we show here that in loading conditions expected in most physiological circumstances the localized reinforcement response fails to scale up to the level of homogeneous cell stretch; fluidization trumps reinforcement. Whereas the reinforcement response is known to be mediated by upstream mechanosensing and downstream signaling, results presented here show the fluidization response to be altogether novel: it is a direct physical effect of mechanical force acting upon a structural lattice that is soft and fragile. Cytoskeletal softness and fragility, we argue, is consistent with early evolutionary adaptations of the eukaryotic cell to material properties of a soft inert microenvironment.

Cytoskeletal proteins from human skin fibroblasts, peripheral blood leukocytes, and a lymphoblastoid cell line compared by two-dimensional gel electrophoresis

International Nuclear Information System (INIS)

Giometti, C.S.; Willard, K.E.; Anderson, N.L.

1982-01-01

Differences in proteins between cells grown as suspension cultures and those grown as attached cultures were studied by comparing the proteins of detergent-resistant cytoskeletons prepared from peripheral blood leukocytes and a lymphoblastoid cell line (GM607) (both grown as suspension cultures) and those of human skin fibroblasts (grown as attached cultures) by two-dimensional gel electrophoresis. The major cytoskeletal proteins of the leukocytes were also present in the protein pattern of GM607 cytoskeletons. In contrast, the fibroblast cytoskeletal protein pattern contained four groups of proteins that differed from the patterns of the leukocytes and GM607. In addition, surface labeling of GM607 and human fibroblasts with 125 I demonstrated that substantial amounts of vimentin and actin are exposed at the surface of the attached fibroblasts, but there is little evidence of similar exposure at the surface of the suspension-grown GM607. These results demonstrate some differences in cytoskeletal protein composition between different types of cells could be related to their ability or lack of ability to grow as attached cells in tissue culture

cAMP/PKA signalling reinforces the LATS–YAP pathway to fully suppress YAP in response to actin cytoskeletal changes

Science.gov (United States)

Kim, Minchul; Kim, Miju; Lee, Seunghee; Kuninaka, Shinji; Saya, Hideyuki; Lee, Ho; Lee, Sookyung; Lim, Dae-Sik

2013-01-01

Actin cytoskeletal damage induces inactivation of the oncoprotein YAP (Yes-associated protein). It is known that the serine/threonine kinase LATS (large tumour suppressor) inactivates YAP by phosphorylating its Ser127 and Ser381 residues. However, the events downstream of actin cytoskeletal changes that are involved in the regulation of the LATS–YAP pathway and the mechanism by which LATS differentially phosphorylates YAP on Ser127 and Ser381 in vivo have remained elusive. Here, we show that cyclic AMP (cAMP)-dependent protein kinase (PKA) phosphorylates LATS and thereby enhances its activity sufficiently to phosphorylate YAP on Ser381. We also found that PKA activity is involved in all contexts previously reported to trigger the LATS–YAP pathway, including actin cytoskeletal damage, G-protein-coupled receptor activation, and engagement of the Hippo pathway. Inhibition of PKA and overexpression of YAP cooperate to transform normal cells and amplify neural progenitor pools in developing chick embryos. We also implicate neurofibromin 2 as an AKAP (A-kinase-anchoring protein) scaffold protein that facilitates the function of the cAMP/PKA–LATS–YAP pathway. Our study thus incorporates PKA as novel component of the Hippo pathway. PMID:23644383

Intracellular Transport of Cargo in a Sub-diffusive Environment over an Explicit Cytoskeletal Network

Science.gov (United States)

Maelfeyt, Bryan; Gopinathan, Ajay

Intracellular transport occurs in nearly all eukaryotic cells, where materials such as proteins, lipids, carbohydrates, and nucleic acids travel to target locations through phases of passive, diffusion-based transport and active, motor-driven transport along filaments that make up the cell's cytoskeleton.We develop a computational model of the process with explicit cytoskeletal filament networks. In the active transport phase, cargo moves in straight lines along these filaments that are spread throughout the cell. To model the passive transport phase of cargo in the cytoplasm, where anomalous sub-diffusion is thought to take place, we implement a continuous-time random walk. We use this approach to provide a stepping stone to a predictive model where we can determine transport properties over a cytoskeletal network provided by experimental images of real filaments. We illustrate our approach by modeling the transport of insulin out of the cell and determining the impact of network geometry, anomalous sub-diffusion and motor number on the first-passage time distributions for insulin granules reaching their target destinations on the membrane.

Disturbed flow mediated modulation of shear forces on endothelial plane: A proposed model for studying endothelium around atherosclerotic plaques

Science.gov (United States)

Balaguru, Uma Maheswari; Sundaresan, Lakshmikirupa; Manivannan, Jeganathan; Majunathan, Reji; Mani, Krishnapriya; Swaminathan, Akila; Venkatesan, Saravanakumar; Kasiviswanathan, Dharanibalan; Chatterjee, Suvro

2016-06-01

Disturbed fluid flow or modulated shear stress is associated with vascular conditions such as atherosclerosis, thrombosis, and aneurysm. In vitro simulation of the fluid flow around the plaque micro-environment remains a challenging approach. Currently available models have limitations such as complications in protocols, high cost, incompetence of co-culture and not being suitable for massive expression studies. Hence, the present study aimed to develop a simple, versatile model based on Computational Fluid Dynamics (CFD) simulation. Current observations of CFD have shown the regions of modulated shear stress by the disturbed fluid flow. To execute and validate the model in real sense, cell morphology, cytoskeletal arrangement, cell death, reactive oxygen species (ROS) profile, nitric oxide production and disturbed flow markers under the above condition were assessed. Endothelium at disturbed flow region which had been exposed to low shear stress and swirling flow pattern showed morphological and expression similarities with the pathological disturbed flow environment reported previously. Altogether, the proposed model can serve as a platform to simulate the real time micro-environment of disturbed flow associated with eccentric plaque shapes and the possibilities of studying its downstream events.

Quinolinic acid neurotoxicity: Differential roles of astrocytes and microglia via FGF-2-mediated signaling in redox-linked cytoskeletal changes.

Science.gov (United States)

Pierozan, Paula; Biasibetti, Helena; Schmitz, Felipe; Ávila, Helena; Parisi, Mariana M; Barbe-Tuana, Florencia; Wyse, Angela T S; Pessoa-Pureur, Regina

2016-12-01

QUIN is a glutamate agonist playing a role in the misregulation of the cytoskeleton, which is associated with neurodegeneration in rats. In this study, we focused on microglial activation, FGF2/Erk signaling, gap junctions (GJs), inflammatory parameters and redox imbalance acting on cytoskeletal dynamics of the in QUIN-treated neural cells of rat striatum. FGF-2/Erk signaling was not altered in QUIN-treated primary astrocytes or neurons, however cytoskeleton was disrupted. In co-cultured astrocytes and neurons, QUIN-activated FGF2/Erk signaling prevented the cytoskeleton from remodeling. In mixed cultures (astrocyte, neuron, microglia), QUIN-induced FGF-2 increased level failed to activate Erk and promoted cytoskeletal destabilization. The effects of QUIN in mixed cultures involved redox imbalance upstream of Erk activation. Decreased connexin 43 (Cx43) immunocontent and functional GJs, was also coincident with disruption of the cytoskeleton in primary astrocytes and mixed cultures. We postulate that in interacting astrocytes and neurons the cytoskeleton is preserved against the insult of QUIN by activation of FGF-2/Erk signaling and proper cell-cell interaction through GJs. In mixed cultures, the FGF-2/Erk signaling is blocked by the redox imbalance associated with microglial activation and disturbed cell communication, disrupting the cytoskeleton. Thus, QUIN signal activates differential mechanisms that could stabilize or destabilize the cytoskeleton of striatal astrocytes and neurons in culture, and glial cells play a pivotal role in these responses preserving or disrupting a combination of signaling pathways and cell-cell interactions. Taken together, our findings shed light into the complex role of the active interaction of astrocytes, neurons and microglia in the neurotoxicity of QUIN. Copyright © 2016 Elsevier B.V. All rights reserved.

Cytoskeletal protein translation and expression in the rat brain are stressor-dependent and region-specific.

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Petra Sántha

Full Text Available Stress is an integral component of life that can sometimes cause a critical overload, depending on the qualitative and quantitative natures of the stressors. The involvement of actin, the predominant component of dendritic integrity, is a plausible candidate factor in stress-induced neuronal cytoskeletal changes. The major aim of this study was to compare the effects of three different stress conditions on the transcription and translation of actin-related cytoskeletal genes in the rat brain. Male Wistar rats were exposed to one or other of the frequently used models of physical stress, i.e. electric foot shock stress (EFSS, forced swimming stress (FSS, or psychosocial stress (PSS for periods of 3, 7, 14, or 21 days. The relative mRNA and protein expressions of β-actin, cofilin and mitogen-activated protein kinase 1 (MAPK-1 were determined by qRT- PCR and western blotting from hippocampus and frontal cortex samples. Stressor-specific alterations in both β-actin and cofilin expression levels were seen after stress. These alterations were most pronounced in response to EFSS, and exhibited a U-shaped time course. FSS led to a significant β-actin mRNA expression elevation in the hippocampus and the frontal cortex after 3 and 7 days, respectively, without any subsequent change. PSS did not cause any change in β-actin or cofilin mRNA or protein expression in the examined brain regions. EFSS, FSS and PSS had no effect on the expression of MAPK-1 mRNA at any tested time point. These findings indicate a very delicate, stress type-dependent regulation of neuronal cytoskeletal components in the rat hippocampus and frontal cortex.

Visual dynamic e-module as a tool to fulfill informational needs and care continuum for diabetic patients

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Mohan Shinde

2015-01-01

Full Text Available Introduction: Diabetes can be envisaged as a lifelong phenomenon having the ominous odds for multisystemic involvement in the duration of disease. The probabilities of the occurrence of these events are influenced by the adopted lifestyle. Hence, information about the disease and lifestyle modification are vital from the perspective of prognostics. This study attempts to explore the potential of a "visual dynamic tool" for imparting knowledge and consequently  received acumen by diabetic patients. Objectives: To appraise the effectiveness of a constructed visual dynamic module (encompassing the various dimensions related to and affected by diabetes by capturing the opinions, perceptions, and experiences of the diabetic patients who underwent intervention through the module. Materials and Methods: A visual e-module with dynamically imposed and animated images in the vernacular (Hindi was prepared. This module was instituted among the diabetic patients in a logical sequence for consecutive 3 days. All the diabetic patients who underwent this intervention were interviewed in depth in order to ascertain the effectiveness of the module. These interviews were analyzed by thematic and framework analyses. Result: The visual module was perceived by the diabetic patients as an optically engaging tool for receiving, connecting, and synthesizing information about diabetes. They sensed and expressed the ease to connect with the images and labeled the received information as inclusive. Conclusion: Initial evidences suggest that visual e-module is an effective and efficient tool for knowledge management in diabetes. This issue may be further explored at diverse academic and clinical settings for gathering more information for efficacy.

Dynamic optical arbitrary waveform shaping based on cascaded optical modulators of single FBG.

Science.gov (United States)

Chen, Jingyuan; Li, Peili

2015-08-10

A dynamic optical arbitrary waveform generation (O-AWG) with amplitude and phase independently controlled in optical modulators of single fiber Bragg Grating (FBG) has been proposed. This novel scheme consists of several optical modulators. In the optical modulator (O-MOD), a uniform FBG is used to filter spectral component of the input signal. The amplitude is controlled by fiber stretcher (FS) in Mach-Zehnder interference (MZI) structure through interference of two MZI arms. The phase is manipulated via the second FS in the optical modulator. This scheme is investigated by simulation. Consequently, optical pulse trains with different waveforms as well as pulse trains with nonuniform pulse intensity, pulse spacing and pulse width within each period are obtained through FSs adjustment to alter the phase shifts of signal in each O-MOD.

Modeling of carrier dynamics in quantum-well electroabsorption modulators

DEFF Research Database (Denmark)

Højfeldt, Sune; Mørk, Jesper

2002-01-01

We present a comprehensive drift-diffusion-type electroabsorption modulator (EAM) model. The model allows us to investigate both steady-state properties and to follow the sweep-out of carriers after pulsed optical excitation. Furthermore, it allows for the investigation of the influence that vari...... in the field near each well affect the escape of carriers from that well. Finally, we look at the influence that the separate-confinement heterostructure barriers have on the carrier sweep-out....... that various design parameters have on the device properties, in particular how they affect the carrier dynamics and the corresponding field dynamics. A number of different types of results are presented. We calculate absorption spectra and steady-state field screening due to carrier pile-up at the separate......-confinement heterobarriers. We then move on to look at carrier sweep-out upon short-pulse optical excitation. For a structure with one well, we analyze how the well position affects the carrier sweep-out and the absorption recovery. We calculate the field dynamics in a multiquantum-well structure and discuss how the changes...

Multicompartment Drug Release System for Dynamic Modulation of Tissue Responses.

Science.gov (United States)

Morris, Aaron H; Mahal, Rajwant S; Udell, Jillian; Wu, Michelle; Kyriakides, Themis R

2017-10-01

Pharmacological modulation of responses to injury is complicated by the need to deliver multiple drugs with spatiotemporal resolution. Here, a novel controlled delivery system containing three separate compartments with each releasing its contents over different timescales is fabricated. Core-shell electrospun fibers create two of the compartments in the system, while electrosprayed spheres create the third. Utility is demonstrated by targeting the foreign body response to implants because it is a dynamic process resulting in implant failure. Sequential delivery of a drug targeting nuclear factor-κB (NF-κB) and an antifibrotic is characterized in in vitro experiments. Specifically, macrophage fusion and p65 nuclear translocation in the presence of releasate or with macrophages cultured on the surfaces of the constructs are evaluated. In addition, releasate from pirfenidone scaffolds is shown to reduce transforming growth factor-β (TGF-β)-induced pSMAD3 nuclear localization in fibroblasts. In vivo, drug eluting constructs successfully mitigate macrophage fusion at one week and fibrotic encapsulation in a dose-dependent manner at four weeks, demonstrating effective release of both drugs over different timescales. Future studies can employ this system to improve and prolong implant lifetimes, or load it with other drugs to modulate other dynamic processes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Progressive supranuclear palsy: neuronal and glial cytoskeletal pathology in the higher order processing autonomic nuclei of the lower brainstem.

Science.gov (United States)

Rüb, U; Del Tredici, K; Schultz, C; de Vos, R A I; Jansen Steur, E N H; Arai, K; Braak, H

2002-02-01

The medial and lateral parabrachial nuclei (MPB, LPB), the gigantocellular reticular nucleus (GI), the raphes magnus (RMG) and raphes obscurus nuclei (ROB), as well as the intermediate reticular zone (IRZ) represent pivotal subordinate brainstem centres, all of which control autonomic functions. In this study, we investigated the occurrence and severity of the neuronal and glial cytoskeletal pathology in these six brainstem nuclei from 17 individuals with clinically diagnosed and neuropathologically confirmed progressive supranuclear palsy (PSP). The association between the severity of the pathology and the duration of the disease was investigated by means of correlation analysis. The brainstem nuclei in all of the PSP cases were affected by the neuronal cytoskeletal pathology, with the IRZ and GI regularly showing severe involvement, the MPB, RMG, and ROB marked involvement, and the LPB mild involvement. In the six nuclear greys studied, glial cells undergo alterations of their cytoskeleton on an irregular basis, whereby diseased oligodendrocytes predominantly presented as coiled bodies and affected astrocytes as thorn-shaped astrocytes. In all six nuclei, the severity of the neuronal or glial cytoskeletal pathology showed no correlation with the duration of PSP. In view of their functional role, the neuronal pathology in the nuclei studied offers a possible explanation for the autonomic dysfunctions that eventually develop in the course of PSP.

Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure

Science.gov (United States)

Maniotis, A. J.; Chen, C. S.; Ingber, D. E.

1997-01-01

We report here that living cells and nuclei are hard-wired such that a mechanical tug on cell surface receptors can immediately change the organization of molecular assemblies in the cytoplasm and nucleus. When integrins were pulled by micromanipulating bound microbeads or micropipettes, cytoskeletal filaments reoriented, nuclei distorted, and nucleoli redistributed along the axis of the applied tension field. These effects were specific for integrins, independent of cortical membrane distortion, and were mediated by direct linkages between the cytoskeleton and nucleus. Actin microfilaments mediated force transfer to the nucleus at low strain; however, tearing of the actin gel resulted with greater distortion. In contrast, intermediate filaments effectively mediated force transfer to the nucleus under both conditions. These filament systems also acted as molecular guy wires to mechanically stiffen the nucleus and anchor it in place, whereas microtubules acted to hold open the intermediate filament lattice and to stabilize the nucleus against lateral compression. Molecular connections between integrins, cytoskeletal filaments, and nuclear scaffolds may therefore provide a discrete path for mechanical signal transfer through cells as well as a mechanism for producing integrated changes in cell and nuclear structure in response to changes in extracellular matrix adhesivity or mechanics.

Mycoplasma pneumoniae Cytoskeletal Protein HMW2 and the Architecture of the Terminal Organelle▿

OpenAIRE

Bose, Stephanie R.; Balish, Mitchell F.; Krause, Duncan C.

2009-01-01

The terminal organelle of Mycoplasma pneumoniae mediates cytadherence and gliding motility and functions in cell division. The defining feature of this complex membrane-bound cell extension is an electron-dense core of two segmented rods oriented longitudinally and enlarging to form a bulb at the distal end. While the components of the core have not been comprehensively identified, previous evidence suggested that the cytoskeletal protein HMW2 forms parallel bundles oriented lengthwise to yie...

ECM-dependent HIF induction directs trophoblast stem cell fate via LIMK1-mediated cytoskeletal rearrangement.

Directory of Open Access Journals (Sweden)

Hwa J Choi

Full Text Available The Hypoxia-inducible Factor (HIF family of transcriptional regulators coordinates the expression of dozens of genes in response to oxygen deprivation. Mammalian development occurs in a hypoxic environment and HIF-null mice therefore die in utero due to multiple embryonic and placental defects. Mouse embryonic stem cells do not differentiate into placental cells; therefore, trophoblast stem cells (TSCs are used to study mouse placental development. Consistent with a requirement for HIF activity during placental development in utero, TSCs derived from HIF-null mice exhibit severe differentiation defects and fail to form trophoblast giant cells (TGCs in vitro. Interestingly, differentiating TSCs induce HIF activity independent of oxygen tension via unclear mechanisms. Here, we show that altering the extracellular matrix (ECM composition upon which TSCs are cultured changes their differentiation potential from TGCs to multinucleated syncytiotropholasts (SynTs and blocks oxygen-independent HIF induction. We further find that modulation of Mitogen Activated Protein Kinase Kinase-1/2 (MAP2K1/2, MEK-1/2 signaling by ECM composition is responsible for this effect. In the absence of ECM-dependent cues, hypoxia-signaling pathways activate this MAPK cascade to drive HIF induction and redirect TSC fate along the TGC lineage. In addition, we show that integrity of the microtubule and actin cytoskeleton is critical for TGC fate determination. HIF-2α ensures TSC cytoskeletal integrity and promotes invasive TGC formation by interacting with c-MYC to induce non-canonical expression of Lim domain kinase 1-an enzyme that regulates microtubule and actin stability, as well as cell invasion. Thus, we find that HIF can integrate positional and metabolic cues from within the TSC niche to regulate placental development by modulating the cellular cytoskeleton via non-canonical gene expression.

Relaxation dynamics of glass transition in PMMA + SWCNT composites by temperature-modulated DSC

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Pradhan, N. R.; Iannacchione, G. S.

2010-03-01

The experimental technique offered by temperature-modulated differential scanning calorimeter (TMDSC) used to investigate the thermal relaxation dynamics through the glass transition as a function of frequency was studied for pure PMMA and PMMA-single wall carbon nanotubes (SWCNTs) composites. A strong dependence of the temperature dependence peak in the imaginary part of complex heat capacity (Tmax) is found during the transition from the glass-like to the liquid-like region. The frequency dependence of Tmax of the imaginary part of heat capacity (Cp) is described by Arrhenius law. The activation energy obtained from the fitting shows increases while the characteristic relaxation time decreases with increasing mass fraction (phim) of SWCNTs. The dynamics of the composites during glass transition, at slow and high scan rates, are also the main focus of this experimental study. The change in enthalpy during heating and cooling is also reported as a function of scan rate and frequency of temperature modulation. The glass transition temperature (Tg) shows increases with increasing frequency of temperature modulation and phim of SWCNTs inside the polymer host. Experimental results show that Tg is higher at higher scan rates but as the frequency of temperature modulation increases, the Tg values of different scan rates coincide with each other and alter the scan rate dependence. From the imaginary part of heat capacity, it is obvious that Tmax is not the actual glass transition temperature of pure polymer but Tmax and Tg values can be superimposed when phim increases in the polymer host or when the sample undergoes a transition with a certain frequency of temperature modulation.

Implementation of a Research-Based Lab Module in a High School Chemistry Curriculum: A Study of Classroom Dynamics

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Pilarz, Matthew

2013-01-01

For this study, a research-based lab module was implemented in two high school chemistry classes for the purpose of examining classroom dynamics throughout the process of students completing the module. A research-based lab module developed for use in undergraduate laboratories by the Center for Authentic Science Practice in Education (CASPiE) was…

A composite role of vitronectin and urokinase in the modulation of cell morphology upon expression of the urokinase receptor

DEFF Research Database (Denmark)

Hillig, Thore; Engelholm, Lars H; Ingvarsen, Signe

2008-01-01

The urokinase receptor, urokinase receptor (uPAR), is a glycosylphosphatidylinositol-anchored membrane protein engaged in pericellular proteolysis and cellular adhesion, migration, and modulation of cell morphology. A direct matrix adhesion is mediated through the binding of uPAR to vitronectin......, and this event is followed by downstream effects including changes in the cytoskeletal organization. However, it remains unclear whether the adhesion through uPAR-vitronectin is the only event capable of initiating these morphological rearrangements or whether lateral interactions between uPAR and integrins can...... a different single-site mutant, uPAR(Y57A), in the presence of a synthetic uPAR-binding peptide, as well as with wild-type uPAR, which underwent cytoskeletal rearrangements even when cultivated in uPA-deficient serum. Blocking of integrins with an Arg-Gly-Asp-containing peptide counteracted the matrix...

On the origins of the universal dynamics of endogenous granules in mammalian cells.

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Vanapalli, Siva A; Li, Yixuan; Mugele, Frieder; Duits, Michel H G

2009-12-01

Endogenous granules (EGs) that consist of lipid droplets and mitochondria have been commonly used to assess intracellular mechanical properties via multiple particle tracking microrheology (MPTM). Despite their widespread use, the nature of interaction of EGs with the cytoskeletal network and the type of forces driving their dynamics--both of which are crucial for the interpretation of the results from MPTM technique--are yet to be resolved. In this report, we study the dynamics of endogenous granules in mammalian cells using particle tracking methods. We find that the ensemble dynamics of EGs is diffusive in three types of mammalian cells (endothelial cells, smooth muscle cells and fibroblasts), thereby suggesting an apparent universality in their dynamical behavior. Moreover, in a given cell, the amplitude of the mean-squared displacement for EGs is an order of magnitude larger than that of injected particles. This observation along with results from ATP depletion and temperature intervention studies suggests that cytoskeletal active forces drive the dynamics of EGs. To elucidate the dynamical origin of the diffusive-like nonthermal motion, we consider three active force generation mechanisms--molecular motor transport, actomyosin contractility and microtubule polymerization forces. We test these mechanisms using pharmacological interventions. Experimental evidence and model calculations suggest that EGs are intimately linked to microtubules and that microtubule polymerization forces drive their dynamics. Thus, endogenous granules could serve as non-invasive probes for microtubule network dynamics in mammalian cells.

Shifts of Gamma Phase across Primary Visual Cortical Sites Reflect Dynamic Stimulus-Modulated Information Transfer.

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Besserve, Michel; Lowe, Scott C; Logothetis, Nikos K; Schölkopf, Bernhard; Panzeri, Stefano

2015-01-01

Distributed neural processing likely entails the capability of networks to reconfigure dynamically the directionality and strength of their functional connections. Yet, the neural mechanisms that may allow such dynamic routing of the information flow are not yet fully understood. We investigated the role of gamma band (50-80 Hz) oscillations in transient modulations of communication among neural populations by using measures of direction-specific causal information transfer. We found that the local phase of gamma-band rhythmic activity exerted a stimulus-modulated and spatially-asymmetric directed effect on the firing rate of spatially separated populations within the primary visual cortex. The relationships between gamma phases at different sites (phase shifts) could be described as a stimulus-modulated gamma-band wave propagating along the spatial directions with the largest information transfer. We observed transient stimulus-related changes in the spatial configuration of phases (compatible with changes in direction of gamma wave propagation) accompanied by a relative increase of the amount of information flowing along the instantaneous direction of the gamma wave. These effects were specific to the gamma-band and suggest that the time-varying relationships between gamma phases at different locations mark, and possibly causally mediate, the dynamic reconfiguration of functional connections.

Using nonlinearity and spatiotemporal property modulation to control effective structural properties: dynamic rods

DEFF Research Database (Denmark)

Thomsen, Jon Juel; Blekhman, Iliya I.

2007-01-01

What are the effective properties of a generally nonlinear material or structure, whose local properties are modulated in both space and time? It has been suggested to use spatiotemporal modulation of structural properties to create materials and structures with adjustable effective properties......, and to call these dynamic materials or spatiotemporal composites. Also, according to theoretical predictions, structural nonlinearity enhances the possibilities of achieving specific effective properties. For example, with an elastic rod having cubical elastic nonlinearities, it seems possible to control......, and exemplified. Then simple approximate analytical expressions are derived for the effective wave speed and natural frequencies for one-dimensional wave propagation in a nonlinear elastic rod, where the spatiotemporal modulation is imposed as a high-frequency standing wave, supposed to be given. Finally the more...

MDA-9/Syntenin (SDCBP) modulates small GTPases RhoA and Cdc42 via transforming growth factor β1 to enhance epithelial-mesenchymal transition in breast cancer.

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Menezes, Mitchell E; Shen, Xue-Ning; Das, Swadesh K; Emdad, Luni; Sarkar, Devanand; Fisher, Paul B

2016-12-06

Epithelial-mesenchymal transition (EMT) is one of the decisive steps regulating cancer invasion and metastasis. However, the molecular mechanisms underlying this transition require further clarification. MDA-9/syntenin (SDCBP) expression is elevated in breast cancer patient samples as well as cultured breast cancer cells. Silencing expression of MDA-9 in mesenchymal metastatic breast cancer cells triggered a change in cell morphology in both 2D- and 3D-cultures to a more epithelial-like phenotype, along with changes in EMT markers, cytoskeletal rearrangement and decreased invasion. Conversely, over expressing MDA-9 in epithelial non-metastatic breast cancer cells instigated a change in morphology to a more mesenchymal phenotype with corresponding changes in EMT markers, cytoskeletal rearrangement and an increase in invasion. We also found that MDA-9 upregulated active levels of known modulators of EMT, the small GTPases RhoA and Cdc42, via TGFβ1. Reintroducing TGFβ1 in MDA-9 silenced cells restored active RhoA and cdc42 levels, modulated cytoskeletal rearrangement and increased invasion. We further determined that MDA-9 interacts with TGFβ1 via its PDZ1 domain. Finally, in vivo studies demonstrated that silencing the expression of MDA-9 resulted in decreased lung metastasis and TGFβ1 re-expression partially restored lung metastases. Our findings provide evidence for the relevance of MDA-9 in mediating EMT in breast cancer and support the potential of MDA-9 as a therapeutic target against metastatic disease.

Biallelic Mutations in TBCD, Encoding the Tubulin Folding Cofactor D, Perturb Microtubule Dynamics and Cause Early-Onset Encephalopathy

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Flex, Elisabetta; Niceta, Marcello; Cecchetti, Serena; Thiffault, Isabelle; Au, Margaret G.; Capuano, Alessandro; Piermarini, Emanuela; Ivanova, Anna A.; Francis, Joshua W.; Chillemi, Giovanni; Chandramouli, Balasubramanian; Carpentieri, Giovanna; Haaxma, Charlotte A.; Ciolfi, Andrea; Pizzi, Simone; Douglas, Ganka V.; Levine, Kara; Sferra, Antonella; Dentici, Maria Lisa; Pfundt, Rolph R.; Le Pichon, Jean-Baptiste; Farrow, Emily; Baas, Frank; Piemonte, Fiorella; Dallapiccola, Bruno; Graham, John M.; Saunders, Carol J.; Bertini, Enrico; Kahn, Richard A.; Koolen, David A.; Tartaglia, Marco

2016-01-01

Microtubules are dynamic cytoskeletal elements coordinating and supporting a variety of neuronal processes, including cell division, migration, polarity, intracellular trafficking, and signal transduction. Mutations in genes encoding tubulins and microtubule-associated proteins are known to cause

Cytoskeletal Regulation Dominates Temperature-Sensitive Proteomic Changes of Hibernation in Forebrain of 13-Lined Ground Squirrels

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Hindle, Allyson G.; Martin, Sandra L.

2013-01-01

13-lined ground squirrels, Ictidomys tridecemlineatus, are obligate hibernators that transition annually between summer homeothermy and winter heterothermy – wherein they exploit episodic torpor bouts. Despite cerebral ischemia during torpor and rapid reperfusion during arousal, hibernator brains resist damage and the animals emerge neurologically intact each spring. We hypothesized that protein changes in the brain underlie winter neuroprotection. To identify candidate proteins, we applied a sensitive 2D gel electrophoresis method to quantify protein differences among forebrain extracts prepared from ground squirrels in two summer, four winter and fall transition states. Proteins that differed among groups were identified using LC-MS/MS. Only 84 protein spots varied significantly among the defined states of hibernation. Protein changes in the forebrain proteome fell largely into two reciprocal patterns with a strong body temperature dependence. The importance of body temperature was tested in animals from the fall; these fall animals use torpor sporadically with body temperatures mirroring ambient temperatures between 4 and 21°C as they navigate the transition between summer homeothermy and winter heterothermy. Unlike cold-torpid fall ground squirrels, warm-torpid individuals strongly resembled the homeotherms, indicating that the changes observed in torpid hibernators are defined by body temperature, not torpor per se. Metabolic enzymes were largely unchanged despite varied metabolic activity across annual and torpor-arousal cycles. Instead, the majority of the observed changes were cytoskeletal proteins and their regulators. While cytoskeletal structural proteins tended to differ seasonally, i.e., between summer homeothermy and winter heterothermy, their regulatory proteins were more strongly affected by body temperature. Changes in the abundance of various isoforms of the microtubule assembly and disassembly regulatory proteins dihydropyrimidinase

Cytoskeletal regulation dominates temperature-sensitive proteomic changes of hibernation in forebrain of 13-lined ground squirrels.

Directory of Open Access Journals (Sweden)

Allyson G Hindle

Full Text Available 13-lined ground squirrels, Ictidomys tridecemlineatus, are obligate hibernators that transition annually between summer homeothermy and winter heterothermy - wherein they exploit episodic torpor bouts. Despite cerebral ischemia during torpor and rapid reperfusion during arousal, hibernator brains resist damage and the animals emerge neurologically intact each spring. We hypothesized that protein changes in the brain underlie winter neuroprotection. To identify candidate proteins, we applied a sensitive 2D gel electrophoresis method to quantify protein differences among forebrain extracts prepared from ground squirrels in two summer, four winter and fall transition states. Proteins that differed among groups were identified using LC-MS/MS. Only 84 protein spots varied significantly among the defined states of hibernation. Protein changes in the forebrain proteome fell largely into two reciprocal patterns with a strong body temperature dependence. The importance of body temperature was tested in animals from the fall; these fall animals use torpor sporadically with body temperatures mirroring ambient temperatures between 4 and 21°C as they navigate the transition between summer homeothermy and winter heterothermy. Unlike cold-torpid fall ground squirrels, warm-torpid individuals strongly resembled the homeotherms, indicating that the changes observed in torpid hibernators are defined by body temperature, not torpor per se. Metabolic enzymes were largely unchanged despite varied metabolic activity across annual and torpor-arousal cycles. Instead, the majority of the observed changes were cytoskeletal proteins and their regulators. While cytoskeletal structural proteins tended to differ seasonally, i.e., between summer homeothermy and winter heterothermy, their regulatory proteins were more strongly affected by body temperature. Changes in the abundance of various isoforms of the microtubule assembly and disassembly regulatory proteins

Surface dynamics in allosteric regulation of protein-protein interactions: modulation of calmodulin functions by Ca2+.

Directory of Open Access Journals (Sweden)

Yosef Y Kuttner

2013-04-01

Full Text Available Knowledge of the structural basis of protein-protein interactions (PPI is of fundamental importance for understanding the organization and functioning of biological networks and advancing the design of therapeutics which target PPI. Allosteric modulators play an important role in regulating such interactions by binding at site(s orthogonal to the complex interface and altering the protein's propensity for complex formation. In this work, we apply an approach recently developed by us for analyzing protein surfaces based on steered molecular dynamics simulation (SMD to the study of the dynamic properties of functionally distinct conformations of a model protein, calmodulin (CaM, whose ability to interact with target proteins is regulated by the presence of the allosteric modulator Ca(2+. Calmodulin is a regulatory protein that acts as an intracellular Ca(2+ sensor to control a wide variety of cellular processes. We demonstrate that SMD analysis is capable of pinpointing CaM surfaces implicated in the recognition of both the allosteric modulator Ca(2+ and target proteins. Our analysis of changes in the dynamic properties of the CaM backbone elicited by Ca(2+ binding yielded new insights into the molecular mechanism of allosteric regulation of CaM-target interactions.

Early cytoskeletal protein modifications precede overt structural degeneration in the DBA/2J mouse model of glaucoma

Directory of Open Access Journals (Sweden)

Gina Nicole Wilson

2016-11-01

Full Text Available Axonal transport deficits precede structural loss in glaucoma and other neurodegenerations. Impairments in structural support, including modified cytoskeletal proteins and microtubule-destabilizing elements, could be initiating factors in glaucoma pathogenesis. We investigated the time course of changes in protein levels and post-translational modifications in the DBA/2J mouse model of glaucoma. Using anterograde tract tracing of the retinal projection, we assessed major cytoskeletal and transported elements as a function of transport integrity in different stages of pathological progression. Using capillary-based electrophoresis, single- and multiplex immunosorbent assays, and immunofluorescence, we quantified hyperphosphorylated neurofilament-heavy chain, phosphorylated tau (ptau, calpain-mediated spectrin breakdown product (145/150kDa, β –tubulin, and amyloid-β42 proteins based on age and transport outcome to the superior colliculus (SC, the main retinal target in mice. Phosphorylated neurofilament-heavy chain (pNF-H was elevated within the optic nerve (ON and SC of 8-10 month-old DBA/2J mice, but was not evident in the retina until 12-15 months, suggesting that cytoskeletal modifications first appear in the distal retinal projection. As expected, higher pNF-H levels in the SC and retina were correlated with axonal transport deficits. Elevations in hyperphosphorylated tau (ptau occurred in ON and SC between 3-8 month of age while retinal ptau accumulations occurred at 12-15 months in DBA/2J mice. In vitro co-immunoprecipitation experiments suggested increased affinity of ptau for the retrograde motor complex protein, dynactin. We observed a transport-related decrease of β-tubulin in ON of 10-12 month-old DBA/2J mice, suggesting destabilized microtubule array. Elevations in calpain-mediated spectrin breakdown product were seen in ON and SC at the earliest age examined, well before axonal transport loss is evident. Finally, transport

Cytoskeleton dynamics: Fluctuations within the network

International Nuclear Information System (INIS)

Bursac, Predrag; Fabry, Ben; Trepat, Xavier; Lenormand, Guillaume; Butler, James P.; Wang, Ning; Fredberg, Jeffrey J.; An, Steven S.

2007-01-01

Out-of-equilibrium systems, such as the dynamics of a living cytoskeleton (CSK), are inherently noisy with fluctuations arising from the stochastic nature of the underlying biochemical and molecular events. Recently, such fluctuations within the cell were characterized by observing spontaneous nano-scale motions of an RGD-coated microbead bound to the cell surface [Bursac et al., Nat. Mater. 4 (2005) 557-561]. While these reported anomalous bead motions represent a molecular level reorganization (remodeling) of microstructures in contact with the bead, a precise nature of these cytoskeletal constituents and forces that drive their remodeling dynamics are largely unclear. Here, we focused upon spontaneous motions of an RGD-coated bead and, in particular, assessed to what extent these motions are attributable to (i) bulk cell movement (cell crawling), (ii) dynamics of focal adhesions, (iii) dynamics of lipid membrane, and/or (iv) dynamics of the underlying actin CSK driven by myosin motors

Tissue architecture and function: dynamic reciprocity via extra- and intra-cellular matrices

Energy Technology Data Exchange (ETDEWEB)

Xu, Ren; Boudreau, Aaron; Bissell, Mina J

2008-12-23

Mammary gland development, functional differentiation, and homeostasis are orchestrated and sustained by a balance of biochemical and biophysical cues from the organ's microenvironment. The three-dimensional microenvironment of the mammary gland, predominantly 'encoded' by a collaboration between the extracellular matrix (ECM), hormones, and growth factors, sends signals from ECM receptors through the cytoskeletal intracellular matrix to nuclear and chromatin structures resulting in gene expression; the ECM in turn is regulated and remodeled by signals from the nucleus. In this chapter, we discuss how coordinated ECM deposition and remodeling is necessary for mammary gland development, how the ECM provides structural and biochemical cues necessary for tissue-specific function, and the role of the cytoskeleton in mediating the extra - to intracellular dialogue occurring between the nucleus and the microenvironment. When operating normally, the cytoskeletal-mediated dynamic and reciprocal integration of tissue architecture and function directs mammary gland development, tissue polarity, and ultimately, tissue-specific gene expression. Cancer occurs when these dynamic interactions go awry for an extended time.

Cytoskeletal dynamics in interphase, mitosis and cytokinesis analysed through Agrobacterium-mediated transient transformation of tobacco BY-2 cells.

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Buschmann, H; Green, P; Sambade, A; Doonan, J H; Lloyd, C W

2011-04-01

Transient transformation with Agrobacterium is a widespread tool allowing rapid expression analyses in plants. However, the available methods generate expression in interphase and do not allow the routine analysis of dividing cells. Here, we present a transient transformation method (termed 'TAMBY2') to enable cell biological studies in interphase and cell division. Agrobacterium-mediated transient gene expression in tobacco BY-2 was analysed by Western blotting and quantitative fluorescence microscopy. Time-lapse microscopy of cytoskeletal markers was employed to monitor cell division. Double-labelling in interphase and mitosis enabled localization studies. We found that the transient transformation efficiency was highest when BY-2/Agrobacterium co-cultivation was performed on solid medium. Transformants produced in this way divided at high frequency. We demonstrated the utility of the method by defining the behaviour of a previously uncharacterized microtubule motor, KinG, throughout the cell cycle. Our analyses demonstrated that TAMBY2 provides a flexible tool for the transient transformation of BY-2 with Agrobacterium. Fluorescence double-labelling showed that KinG localizes to microtubules and to F-actin. In interphase, KinG accumulates on microtubule lagging ends, suggesting a minus-end-directed function in vivo. Time-lapse studies of cell division showed that GFP-KinG strongly labels preprophase band and phragmoplast, but not the metaphase spindle. © 2010 The Authors. New Phytologist © 2010 New Phytologist Trust.

Modal resonant dynamics of cables with a flexible support: A modulated diffraction problem

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Guo, Tieding; Kang, Houjun; Wang, Lianhua; Liu, Qijian; Zhao, Yueyu

2018-06-01

Modal resonant dynamics of cables with a flexible support is defined as a modulated (wave) diffraction problem, and investigated by asymptotic expansions of the cable-support coupled system. The support-cable mass ratio, which is usually very large, turns out to be the key parameter for characterizing cable-support dynamic interactions. By treating the mass ratio's inverse as a small perturbation parameter and scaling the cable tension properly, both cable's modal resonant dynamics and the flexible support dynamics are asymptotically reduced by using multiple scale expansions, leading finally to a reduced cable-support coupled model (i.e., on a slow time scale). After numerical validations of the reduced coupled model, cable-support coupled responses and the flexible support induced coupling effects on the cable, are both fully investigated, based upon the reduced model. More explicitly, the dynamic effects on the cable's nonlinear frequency and force responses, caused by the support-cable mass ratio, the resonant detuning parameter and the support damping, are carefully evaluated.

Observation Platform for Dynamic Biomedical and Biotechnology Experiments using the ISS Light Microscopy Module, Phase I

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National Aeronautics and Space Administration — The proposed "Observation platform for dynamic biomedical and biotechnology experiments using the ISS Light Microscopy Module" consists of a platen sized to fit the...

Construction of a dynamic model for a PEM power module with applications to distributed power generation. Paper no. IGEC-1-086

International Nuclear Information System (INIS)

Zhang, Z.; Jiang, J.; Wu, B.

2005-01-01

This paper deals with dynamic model construction for a PEM fuel cell power module with potential applications for distributed power generation. In particular, the effects of temperature and variations in the internal impedance as load changes have been considered. Analytical models are synthesized first by using the measurements taken at different operating conditions, and then these models are validated by performing static as well as dynamic tests on the fuel cells. The results have indicated that the models indeed represent the dynamic behaviour of the fuel cell power module accurately. (author)

TiO2 nanoparticles disrupt cell adhesion and the architecture of cytoskeletal networks of human osteoblast-like cells in a size dependent manner.

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Ibrahim, Mohamed; Schoelermann, Julia; Mustafa, Kamal; Cimpan, Mihaela R

2018-04-30

Human exposure to titanium dioxide nanoparticles (nano-TiO 2 ) is increasing. An internal source of nano-TiO 2 is represented by titanium-based orthopedic and dental implants can release nanoparticles (NPs) upon abrasion. Little is known about how the size of NPs influences their interaction with cytoskeletal protein networks and the functional/homeostatic consequences that might follow at the implant-bone interface with regard to osteoblasts. We investigated the effects of size of anatase nano-TiO 2 on SaOS-2 human osteoblast-like cells exposed to clinically relevant concentrations (0.05, 0.5, 5 mg/L) of 5 and 40 nm spherical nano-TiO 2 . Cell viability and proliferation, adhesion, spread and migration were assessed, as well as the orientation of actin and microtubule cytoskeletal networks. The phosphorylation of focal adhesion kinase (p-FAK Y397 ) and the expression of vinculin in response to nano-TiO 2 were also assessed. Treatment with nano-TiO 2 disrupted the actin and microtubule cytoskeletal networks leading to morphological modifications of SaOS-2 cells. The phosphorylation of p-FAK Y397 and the expression of vinculin were also modified depending on the particle size, which affected cell adhesion. Consequently, the cell migration was significantly impaired in the 5 nm-exposed cells compared to unexposed cells. The present work shows that the orientation of cytoskeletal networks and the focal adhesion proteins and subsequently the adhesion, spread and migration of SaOS-2 cells were affected by the selected nano-TiO 2 in a size dependent manner. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Novelty-induced activity-regulated cytoskeletal-associated protein (Arc) expression in frontal cortex requires serotonin 2A receptor activation

DEFF Research Database (Denmark)

Santini, Martin; Klein, A B; El-Sayed, M

2011-01-01

environment. As an output of FC activation we measured expression of activity-regulated cytoskeletal-associated protein (Arc). Novelty-exposure (open-field arena) robustly up-regulated FC Arc mRNA expression (∼160%) in mice compared to home-cage controls. This response was inhibited with the 5-HT(2A...

Novelty-induced activity-regulated cytoskeletal-associated protein (Arc) expression in frontal cortex requires serotonin 2A receptor activation

DEFF Research Database (Denmark)

Santini, Martin; Klein, A B; El-Sayed, M

2011-01-01

environment. As an output of FC activation we measured expression of activity-regulated cytoskeletal-associated protein (Arc). Novelty-exposure (open-field arena) robustly up-regulated FC Arc mRNA expression (~160%) in mice compared to home-cage controls. This response was inhibited with the 5-HT(2A...

SU-E-J-254: Utility of Pinnacle Dynamic Planning Module Utilizing Deformable Image Registration in Adaptive Radiotherapy

International Nuclear Information System (INIS)

Jani, S

2014-01-01

Purpose For certain highly conformal treatment techniques, changes in patient anatomy due to weight loss and/or tumor shrinkage can result in significant changes in dose distribution. Recently, the Pinnacle treatment planning system added a Dynamic Planning module utilizing Deformable Image Registration (DIR). The objective of this study was to evaluate the effectiveness of this software in adapting to altered anatomy and adjusting treatment plans to account for it. Methods We simulated significant tumor response by changing patient thickness and altered chin positions using a commercially-available head and neck (H and N) phantom. In addition, we studied 23 CT image sets of fifteen (15) patients with H and N tumors and eight (8) patients with prostate cancer. In each case, we applied deformable image registration through Dynamic Planning module of our Pinnacle Treatment Planning System. The dose distribution of the original CT image set was compared to the newly computed dose without altering any treatment parameter. Result was a dose if we did not adjust the plan to reflect anatomical changes. Results For the H and N phantom, a tumor response of up to 3.5 cm was correctly deformed by the Pinnacle Dynamic module. Recomputed isodose contours on new anatomies were within 1 mm of the expected distribution. The Pinnacle system configuration allowed dose computations resulting from original plans on new anatomies without leaving the planning system. Original and new doses were available side-by-side with both CT image sets. Based on DIR, about 75% of H and N patients (11/15) required a re-plan using new anatomy. Among prostate patients, the DIR predicted near-correct bladder volume in 62% of the patients (5/8). Conclusions The Dynamic Planning module of the Pinnacle system proved to be an accurate and useful tool in our ability to adapt to changes in patient anatomy during a course of radiotherapy

Exploring protein structure and dynamics through a project-oriented biochemistry laboratory module.

Science.gov (United States)

Lipchock, James M; Ginther, Patrick S; Douglas, Bonnie B; Bird, Kelly E; Patrick Loria, J

2017-09-01

Here, we present a 10-week project-oriented laboratory module designed to provide a course-based undergraduate research experience in biochemistry that emphasizes the importance of biomolecular structure and dynamics in enzyme function. This module explores the impact of mutagenesis on an important active site loop for a biomedically-relevant human enzyme, protein tyrosine phosphatase 1B (PTP1B). Over the course of the semester students guide their own mutant of PTP1B from conception to characterization in a cost-effective manner and gain exposure to fundamental techniques in biochemistry, including site-directed DNA mutagenesis, bacterial recombinant protein expression, affinity column purification, protein quantitation, SDS-PAGE, and enzyme kinetics. This project-based approach allows an instructor to simulate a research setting and prepare students for productive research beyond the classroom. Potential modifications to expand or contract this module are also provided. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(5):403-410, 2017. © 2017 The International Union of Biochemistry and Molecular Biology.

Dynamic modulation of epileptic high frequency oscillations by the phase of slower cortical rhythms.

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Ibrahim, George M; Wong, Simeon M; Anderson, Ryan A; Singh-Cadieux, Gabrielle; Akiyama, Tomoyuki; Ochi, Ayako; Otsubo, Hiroshi; Okanishi, Tohru; Valiante, Taufik A; Donner, Elizabeth; Rutka, James T; Snead, O Carter; Doesburg, Sam M

2014-01-01

Pathological high frequency oscillations (pHFOs) have been proposed to be robust markers of epileptic cortex. Oscillatory activity below this frequency range has been shown to be modulated by phase of lower frequency oscillations. Here, we tested the hypothesis that dynamic cross-frequency interactions involving pHFOs are concentrated within the epileptogenic cortex. Intracranial electroencephalographic recordings from 17 children with medically-intractable epilepsy secondary to focal cortical dysplasia were obtained. A time-resolved analysis was performed to determine topographic concentrations and dynamic changes in cross-frequency amplitude-to-phase coupling (CFC). CFC between pHFOs and the phase of theta and alpha rhythms was found to be significantly elevated in the seizure-onset zone compared to non-epileptic regions (pfrequency oscillations at which pHFO amplitudes were maximal was inconsistent at seizure initiation, yet consistently at the trough of the low frequency rhythm at seizure termination. Amplitudes of pHFOs were most significantly modulated by the phase of alpha-band oscillations (p<0.01). These results suggest that increased CFC between pHFO amplitude and alpha phase may constitute a marker of epileptogenic brain areas and may be relevant for understanding seizure dynamics. Copyright © 2013 Elsevier Inc. All rights reserved.

Development of an empirical dynamic model for a Nexa PEM fuel cell power module

Energy Technology Data Exchange (ETDEWEB)

Soltani, Mehdi; Mohammad Taghi Bathaee, S. [Power Systems Laboratory, Department of Electrical Engineering, K.N. Toosi University of Technology, 16317-14191 Tehran (Iran)

2010-12-15

The goal of this study is to develop a fuel cell model which is capable of characterizing fuel cell steady-state performance as well as dynamic behavior. In this paper a new dynamic model of a 1.2 kW Polymer Electrolyte Membrane Fuel Cell (PEMFC) is developed and validated through a series of experiments. The experimental results have been obtained from a Nexa trademark PEM fuel cell power module under different load conditions. Based on this model, a simulator software package has been developed using the MATLAB {sup registered} and Simulink {sup registered} software and simulation results have been carried out. The proposed model exhibits good agreement with experiment results in steady-state and dynamic performance. (author)

Distribution of cytoskeletal proteins, integrins, leukocyte adhesion molecules and extracellular matrix proteins in plastic-embedded human and rat kidneys

NARCIS (Netherlands)

van Goor, H; Coers, W; van der Horst, MLC; Suurmeijer, AJH

2001-01-01

OBJECTIVE: To study the distribution of cytoskeletal proteins (actin, alpha -actinin, vinculin, beta -tubulin, keratin, vimentin, desmin), adhesion molecules for cell-matrix interations (very later antigens [VLA1-6], beta1, beta2 [CD18], vitronectin receptor [alphav beta3], CD 11b), leukocyte

Induction of Plant Curvature by Magnetophoresis and Cytoskeletal Changes during Root Graviresponse

Science.gov (United States)

Hasenstein, Karl H.; Kuznetsov, Oleg A.; Blancaflor, Eilson B.

1996-01-01

High gradient magnetic fields (HGMF) induce curvature in roots and shoots. It is considered that this response is likely to be based on the intracellular displacement of bulk starch (amyloplasts) by the ponderomotive force generated by the HGMF. This process is called magnetophoresis. The differential elongation during the curvature along the concave and convex flanks of growing organs may be linked to the microtubular and/or microfilament cytoskeleton. The possible existence of an effect of the HGMF on the cytoskeleton was tested for, but none was found. The application of cytoskeletal stabilizers or depolymerizers showed that neither microtubules, nor microfilaments, are involved in the graviresponse.

Dynamic modulation of phosphoprotein expression in ovarian cancer xenograft models

International Nuclear Information System (INIS)

Koussounadis, Antonis; Langdon, Simon P.; Um, Inhwa; Kay, Charlene; Francis, Kyle E.; Harrison, David J.; Smith, V. Anne

2016-01-01

The dynamic changes that occur in protein expression after treatment of a cancer in vivo are poorly described. In this study we measure the effect of chemotherapy over time on the expression of a panel of proteins in ovarian cancer xenograft models. The objective was to identify phosphoprotein and other protein changes indicative of pathway activation that might link with drug response. Two xenograft models, platinum-responsive OV1002 and platinum-unresponsive HOX424, were used. Treatments were carboplatin and carboplatin-paclitaxel. Expression of 49 proteins over 14 days post treatment was measured by quantitative immunofluorescence and analysed by AQUA. Carboplatin treatment in the platinum-sensitive OV1002 model triggered up-regulation of cell cycle, mTOR and DDR pathways, while at late time points WNT, invasion, EMT and MAPK pathways were modulated. Estrogen receptor-alpha (ESR1) and ERBB pathways were down-regulated early, within 24 h from treatment administration. Combined carboplatin-paclitaxel treatment triggered a more extensive response in the OV1002 model modulating expression of 23 of 49 proteins. Therefore the cell cycle and DDR pathways showed similar or more pronounced changes than with carboplatin alone. In addition to expression of pS6 and pERK increasing, components of the AKT pathway were modulated with pAKT increasing while its regulator PTEN was down-regulated early. WNT signaling, EMT and invasion markers were modulated at later time points. Additional pathways were also observed with the NFκB and JAK/STAT pathways being up-regulated. ESR1 was down-regulated as was HER4, while further protein members of the ERBB pathway were upregulated late. By contrast, in the carboplatin-unresponsive HOX 424 xenograft, carboplatin only modulated expression of MLH1 while carboplatin-paclitaxel treatment modulated ESR1 and pMET. Thirteen proteins were modulated by carboplatin and a more robust set of changes by carboplatin-paclitaxel. Early changes included

Structures of a Nonribosomal Peptide Synthetase Module Bound to MbtH-like Proteins Support a Highly Dynamic Domain Architecture

Energy Technology Data Exchange (ETDEWEB)

Miller, Bradley R.; Drake, Eric J.; Shi, Ce; Aldrich, Courtney C.; Gulick, Andrew M. (UMM); (HWMRI)

2016-09-05

Nonribosomal peptide synthetases (NRPSs) produce a wide variety of peptide natural products. During synthesis, the multidomain NRPSs act as an assembly line, passing the growing product from one module to the next. Each module generally consists of an integrated peptidyl carrier protein, an amino acid-loading adenylation domain, and a condensation domain that catalyzes peptide bond formation. Some adenylation domains interact with small partner proteins called MbtH-like proteins (MLPs) that enhance solubility or activity. A structure of an MLP bound to an adenylation domain has been previously reported using a truncated adenylation domain, precluding any insight that might be derived from understanding the influence of the MLP on the intact adenylation domain or on the dynamics of the entire NRPS module. Here, we present the structures of the full-length NRPS EntF bound to the MLPs from Escherichia coli and Pseudomonas aeruginosa. These new structures, along with biochemical and bioinformatics support, further elaborate the residues that define the MLP-adenylation domain interface. Additionally, the structures highlight the dynamic behavior of NRPS modules, including the module core formed by the adenylation and condensation domains as well as the orientation of the mobile thioesterase domain.

Pdlim7 Regulates Arf6-Dependent Actin Dynamics and Is Required for Platelet-Mediated Thrombosis in Mice.

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Alexander E Urban

Full Text Available Upon vessel injury, platelets become activated and rapidly reorganize their actin cytoskeleton to adhere to the site of endothelial damage, triggering the formation of a fibrin-rich plug to prevent further blood loss. Inactivation of Pdlim7 provides the new perspective that regulation of actin cytoskeletal changes in platelets is dependent on the encoded PDZ-LIM protein. Loss-of-function of Pdlim7 triggers hypercoagulopathy and causes significant perinatal lethality in mice. Our in vivo and in vitro studies reveal that Pdlim7 is dynamically distributed along actin fibers, and lack of Pdlim7 leads to a marked inability to rearrange the actin cytoskeleton. Specifically, the absence of Pdlim7 prevents platelets from bundling actin fibers into a concentric ring that defines the round spread shape of activated platelets. Similarly, in mouse embryonic fibroblasts, loss of Pdlim7 abolishes the formation of stress fibers needed to adopt the typical elongated fibroblast shape. In addition to revealing a fundamental cell biological role in actin cytoskeletal organization, we also demonstrate a function of Pdlim7 in regulating the cycling between the GTP/GDP-bound states of Arf6. The small GTPase Arf6 is an essential factor required for actin dynamics, cytoskeletal rearrangements, and platelet activation. Consistent with our findings of significantly elevated initial F-actin ratios and subsequent morphological aberrations, loss of Pdlim7 causes a shift in balance towards an increased Arf6-GTP level in resting platelets. These findings identify a new Pdlim7-Arf6 axis controlling actin dynamics and implicate Pdlim7 as a primary endogenous regulator of platelet-dependent hemostasis.

Drosophila growth cones: a genetically tractable platform for the analysis of axonal growth dynamics.

Science.gov (United States)

Sánchez-Soriano, Natalia; Gonçalves-Pimentel, Catarina; Beaven, Robin; Haessler, Ulrike; Ofner-Ziegenfuss, Lisa; Ballestrem, Christoph; Prokop, Andreas

2010-01-01

The formation of neuronal networks, during development and regeneration, requires outgrowth of axons along reproducible paths toward their appropriate postsynaptic target cells. Axonal extension occurs at growth cones (GCs) at the tips of axons. GC advance and navigation requires the activity of their cytoskeletal networks, comprising filamentous actin (F-actin) in lamellipodia and filopodia as well as dynamic microtubules (MTs) emanating from bundles of the axonal core. The molecular mechanisms governing these two cytoskeletal networks, their cross-talk, and their response to extracellular signaling cues are only partially understood, hindering our conceptual understanding of how regulated changes in GC behavior are controlled. Here, we introduce Drosophila GCs as a suitable model to address these mechanisms. Morphological and cytoskeletal readouts of Drosophila GCs are similar to those of other models, including mammals, as demonstrated here for MT and F-actin dynamics, axonal growth rates, filopodial structure and motility, organizational principles of MT networks, and subcellular marker localization. Therefore, we expect fundamental insights gained in Drosophila to be translatable into vertebrate biology. The advantage of the Drosophila model over others is its enormous amenability to combinatorial genetics as a powerful strategy to address the complexity of regulatory networks governing axonal growth. Thus, using pharmacological and genetic manipulations, we demonstrate a role of the actin cytoskeleton in a specific form of MT organization (loop formation), known to regulate GC pausing behavior. We demonstrate these events to be mediated by the actin-MT linking factor Short stop, thus identifying an essential molecular player in this context.

Cdc42 regulates cofilin during the establishment of neuronal polarity

DEFF Research Database (Denmark)

Garvalov, Boyan K; Flynn, Kevin C; Neukirchen, Dorothee

2007-01-01

suppressed ability to form axons both in vivo and in culture. This was accompanied by disrupted cytoskeletal organization, enlargement of the growth cones, and inhibition of filopodial dynamics. Axon formation in the knock-out neurons was rescued by manipulation of the actin cytoskeleton, indicating...... that the effects of Cdc42 ablation are exerted through modulation of actin dynamics. In addition, the knock-outs showed a specific increase in the phosphorylation (inactivation) of the Cdc42 effector cofilin. Furthermore, the active, nonphosphorylated form of cofilin was enriched in the axonal growth cones of wild...

Modeling cytoskeletal flow over adhesion sites: competition between stochastic bond dynamics and intracellular relaxation

International Nuclear Information System (INIS)

Sabass, Benedikt; Schwarz, Ulrich S

2010-01-01

In migrating cells, retrograde flow of the actin cytoskeleton is related to traction at adhesion sites located at the base of the lamellipodium. The coupling between the moving cytoskeleton and the stationary adhesions is mediated by the continuous association and dissociation of molecular bonds. We introduce a simple model for the competition between the stochastic dynamics of elastic bonds at the moving interface and relaxation within the moving actin cytoskeleton represented by an internal viscous friction coefficient. Using exact stochastic simulations and an analytical mean field theory, we show that the stochastic bond dynamics lead to biphasic friction laws as observed experimentally. At low internal dissipation, stochastic bond dynamics lead to a regime of irregular stick-and-slip motion. High internal dissipation effectively suppresses cooperative effects among bonds and hence stabilizes the adhesion.

Conversational module-based simulation system as a human interface to versatile dynamic simulation of nuclear power plant

International Nuclear Information System (INIS)

Yoshikawa, H.; Nakaya, K.; Wakabayashi, J.

1986-01-01

A new conversational simulation system is proposed which aims at effective re-utilization of software resources as module database, and conducting versatile simulations easily by automatic module integration with the help of user-friendly interfaces. The whole simulation system is composed of the four parts: master module library and pre-compiler system as the core system, while module database management system and simulation execution support system for the user interfaces. Basic methods employed in the system are mentioned with their knowledge representation and the relationship with the human information processing. An example practice of an LMFBR reactor dynamic simulation by the system demonstrated its capability to integrate a large simulation program and the related input/output files automatically by a single user

ATG5 overexpression is neuroprotective and attenuates cytoskeletal and vesicle-trafficking alterations in axotomized motoneurons.

Science.gov (United States)

Leiva-Rodríguez, Tatiana; Romeo-Guitart, David; Marmolejo-Martínez-Artesero, Sara; Herrando-Grabulosa, Mireia; Bosch, Assumpció; Forés, Joaquim; Casas, Caty

2018-05-24

Injured neurons should engage endogenous mechanisms of self-protection to limit neurodegeneration. Enhancing efficacy of these mechanisms or correcting dysfunctional pathways may be a successful strategy for inducing neuroprotection. Spinal motoneurons retrogradely degenerate after proximal axotomy due to mechanical detachment (avulsion) of the nerve roots, and this limits recovery of nervous system function in patients after this type of trauma. In a previously reported proteomic analysis, we demonstrated that autophagy is a key endogenous mechanism that may allow motoneuron survival and regeneration after distal axotomy and suture of the nerve. Herein, we show that autophagy flux is dysfunctional or blocked in degenerated motoneurons after root avulsion. We also found that there were abnormalities in anterograde/retrograde motor proteins, key secretory pathway factors, and lysosome function. Further, LAMP1 protein was missorted and underglycosylated as well as the proton pump v-ATPase. In vitro modeling revealed how sequential disruptions in these systems likely lead to neurodegeneration. In vivo, we observed that cytoskeletal alterations, induced by a single injection of nocodazole, were sufficient to promote neurodegeneration of avulsed motoneurons. Besides, only pre-treatment with rapamycin, but not post-treatment, neuroprotected after nerve root avulsion. In agreement, overexpressing ATG5 in injured motoneurons led to neuroprotection and attenuation of cytoskeletal and trafficking-related abnormalities. These discoveries serve as proof of concept for autophagy-target therapy to halting the progression of neurodegenerative processes.

Organoselenium compounds prevent hyperphosphorylation of cytoskeletal proteins induced by the neurotoxic agent diphenyl ditelluride in cerebral cortex of young rats

International Nuclear Information System (INIS)

Moretto, M.B.; Funchal, C.; Zeni, G.; Rocha, J.B.T.; Pessoa-Pureur, R.

2005-01-01

In this work we investigated the protective ability of the selenium compounds ebselen and diphenyl diselenide against the effect of diphenyl ditelluride on the in vitro incorporation of 32 P into intermediate filament (IF) proteins from slices of cerebral cortex of 17-day-old rats. We observed that ditelluride in the concentrations of 1, 15 and 50 μM induced hyperphosphorylation of the high-salt Triton insoluble neurofilament subunits (NF-M and NF-L), glial fibrillary acidic protein (GFAP) and vimentin, without altering the immunocontent of these proteins. Concerning the selenium compounds, diselenide (1, 15 and 50 μM) did not induce alteration of the in vitro phosphorylation of the IF proteins. Otherwise, ebselen induced an altered in vitro phosphorylation of the cytoskeletal proteins in a dose-dependent manner. At intermediate concentrations (15 and 30 μM) it increased the in vitro phosphorylation even though, at low (5 μM) or high (50 and 100 μM) concentrations this compound was ineffective in altering the activity of the cytoskeletal-associated phosphorylating system. In addition, 15 μM diselenide and 5 μM ebselen, presented a protective effect against the action of ditelluride, on the phosphorylation of the proteins studied. Considering that hyperphosphorylation of cytoskeletal proteins is associated with neuronal dysfunction and neurodegeneration, it is probable that the effects of ditelluride could be related to the remarkable neurotoxicity of this organic form of tellurium. Furthermore the neuroprotective action of selenium compounds against tellurium effects could be a promising route to be exploited for a possible treatment of organic tellurium poisoning

A spatiotemporal characterization method for the dynamic cytoskeleton.

Science.gov (United States)

Alhussein, Ghada; Shanti, Aya; Farhat, Ilyas A H; Timraz, Sara B H; Alwahab, Noaf S A; Pearson, Yanthe E; Martin, Matthew N; Christoforou, Nicolas; Teo, Jeremy C M

2016-05-01

The significant gap between quantitative and qualitative understanding of cytoskeletal function is a pressing problem; microscopy and labeling techniques have improved qualitative investigations of localized cytoskeleton behavior, whereas quantitative analyses of whole cell cytoskeleton networks remain challenging. Here we present a method that accurately quantifies cytoskeleton dynamics. Our approach digitally subdivides cytoskeleton images using interrogation windows, within which box-counting is used to infer a fractal dimension (Df ) to characterize spatial arrangement, and gray value intensity (GVI) to determine actin density. A partitioning algorithm further obtains cytoskeleton characteristics from the perinuclear, cytosolic, and periphery cellular regions. We validated our measurement approach on Cytochalasin-treated cells using transgenically modified dermal fibroblast cells expressing fluorescent actin cytoskeletons. This method differentiates between normal and chemically disrupted actin networks, and quantifies rates of cytoskeletal degradation. Furthermore, GVI distributions were found to be inversely proportional to Df , having several biophysical implications for cytoskeleton formation/degradation. We additionally demonstrated detection sensitivity of differences in Df and GVI for cells seeded on substrates with varying degrees of stiffness, and coated with different attachment proteins. This general approach can be further implemented to gain insights on dynamic growth, disruption, and structure of the cytoskeleton (and other complex biological morphology) due to biological, chemical, or physical stimuli. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Dead zone analysis of ECAL barrel modules under static and dynamic load

Science.gov (United States)

Pierre-Emile, T.; Anduze, M.

2018-03-01

In the context of ILD project, impact studies of environmental loads on the Electromagnetic CALorimeter (ECAL) have been initiated. The ECAL part considered is the barrel and it consists of several independent modules which are mounted on the Hadronic CALorimeter barrel (HCAL) itself mounted on the cryostat coil and the yoke. The estimate of the gap required between each ECAL modules is fundamental to define the assembly step and avoid mechanical contacts over the barrel lifetime. In the meantime, it has to be done in consideration to the dead spaces reduction and detector hermiticity optimization. Several Finite Element Analysis (FEA) with static and dynamic loads have been performed in order to define correctly the minimum values for those gaps. Due to the implantation site of the whole project in Japan, seismic analysis were carried out in addition to the static ones. This article shows results of these analysis done with the Finite Element Method (FEM) in ANSYS. First results show the impact of HCAL design on the ECAL modules motion in static load. The second study dedicated to seismic approach on a larger model (including yoke and cryostat) gives additional results on earthquake consequences.

Scaling dynamic response and destructive metabolism in an immunosurveillant anti-tumor system modulated by different external periodic interventions.

Directory of Open Access Journals (Sweden)

Yuanzhi Shao

Full Text Available On the basis of two universal power-law scaling laws, i.e. the scaling dynamic hysteresis in physics and the allometric scaling metabolism in biosystem, we studied the dynamic response and the evolution of an immunosurveillant anti-tumor system subjected to a periodic external intervention, which is equivalent to the scheme of a radiotherapy or chemotherapy, within the framework of the growth dynamics of tumor. Under the modulation of either an abrupt or a gradual change external intervention, the population density of tumors exhibits a dynamic hysteresis to the intervention. The area of dynamic hysteresis loop characterizes a sort of dissipative-therapeutic relationship of the dynamic responding of treated tumors with the dose consumption of accumulated external intervention per cycle of therapy. Scaling the area of dynamic hysteresis loops against the intensity of an external intervention, we deduced a characteristic quantity which was defined as the theoretical therapeutic effectiveness of treated tumor and related with the destructive metabolism of tumor under treatment. The calculated dose-effectiveness profiles, namely the dose cumulant per cycle of intervention versus the therapeutic effectiveness, could be well scaled into a universal quadratic formula regardless of either an abrupt or a gradual change intervention involved. We present a new concept, i.e., the therapy-effect matrix and the dose cumulant matrix, to expound the new finding observed in the growth and regression dynamics of a modulated anti-tumor system.

Dynamic range of frontoparietal functional modulation is associated with working memory capacity limitations in older adults.

Science.gov (United States)

Hakun, Jonathan G; Johnson, Nathan F

2017-11-01

Older adults tend to over-activate regions throughout frontoparietal cortices and exhibit a reduced range of functional modulation during WM task performance compared to younger adults. While recent evidence suggests that reduced functional modulation is associated with poorer task performance, it remains unclear whether reduced range of modulation is indicative of general WM capacity-limitations. In the current study, we examined whether the range of functional modulation observed over multiple levels of WM task difficulty (N-Back) predicts in-scanner task performance and out-of-scanner psychometric estimates of WM capacity. Within our sample (60-77years of age), age was negatively associated with frontoparietal modulation range. Individuals with greater modulation range exhibited more accurate N-Back performance. In addition, despite a lack of significant relationships between N-Back and complex span task performance, range of frontoparietal modulation during the N-Back significantly predicted domain-general estimates of WM capacity. Consistent with previous cross-sectional findings, older individuals with less modulation range exhibited greater activation at the lowest level of task difficulty but less activation at the highest levels of task difficulty. Our results are largely consistent with existing theories of neurocognitive aging (e.g. CRUNCH) but focus attention on dynamic range of functional modulation asa novel marker of WM capacity-limitations in older adults. Copyright © 2017 Elsevier Inc. All rights reserved.

Volume of interest CBCT and tube current modulation for image guidance using dynamic kV collimation

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Parsons, David, E-mail: david.parsons@dal.ca, E-mail: james.robar@nshealth.ca [Department of Physics and Atmospheric Science, Dalhousie University, 5820 University Avenue, Halifax, Nova Scotia B3H 1V7 (Canada); Robar, James L., E-mail: david.parsons@dal.ca, E-mail: james.robar@nshealth.ca [Department of Radiation Oncology and Department of Physics and Atmospheric Science, Dalhousie University, 5820 University Avenue, Halifax, Nova Scotia B3H 1V7 (Canada)

2016-04-15

Purpose: The focus of this work is the development of a novel blade collimation system enabling volume of interest (VOI) CBCT with tube current modulation using the kV image guidance source on a linear accelerator. Advantages of the system are assessed, particularly with regard to reduction and localization of dose and improvement of image quality. Methods: A four blade dynamic kV collimator was developed to track a VOI during a CBCT acquisition. The current prototype is capable of tracking an arbitrary volume defined by the treatment planner for subsequent CBCT guidance. During gantry rotation, the collimator tracks the VOI with adjustment of position and dimension. CBCT image quality was investigated as a function of collimator dimension, while maintaining the same dose to the VOI, for a 22.2 cm diameter cylindrical water phantom with a 9 mm diameter bone insert centered on isocenter. Dose distributions were modeled using a dynamic BEAMnrc library and DOSXYZnrc. The resulting VOI dose distributions were compared to full-field CBCT distributions to quantify dose reduction and localization to the target volume. A novel method of optimizing x-ray tube current during CBCT acquisition was developed and assessed with regard to contrast-to-noise ratio (CNR) and imaging dose. Results: Measurements show that the VOI CBCT method using the dynamic blade system yields an increase in contrast-to-noise ratio by a factor of approximately 2.2. Depending upon the anatomical site, dose was reduced to 15%–80% of the full-field CBCT value along the central axis plane and down to less than 1% out of plane. The use of tube current modulation allowed for specification of a desired SNR within projection data. For approximately the same dose to the VOI, CNR was further increased by a factor of 1.2 for modulated VOI CBCT, giving a combined improvement of 2.6 compared to full-field CBCT. Conclusions: The present dynamic blade system provides significant improvements in CNR for the same

A 1-V 60-μW 85-dB dynamic range continuous-time third-order sigma-delta modulator

International Nuclear Information System (INIS)

Li Yuanwen; Qi Da; Dong Yifeng; Xu Jun; Ren Junyan

2009-01-01

A 1-V third order one-bit continuous-time (CT) EA modulator is presented. Designed in the SMIC mixed-signal 0.13-μm CMOS process, the modulator utilizes active RC integrators to implement the loop filter. An efficient circuit design methodology for the CT ΣΔ modulator is proposed and verified. Low power dissipation is achieved through the use of two-stage class A/AB amplifiers. The presented modulator achieves 81.4-dB SNDR and 85-dB dynamic range in a 20-kHz bandwidth with an over sampling ratio of 128. The total power consumption of the modulator is only 60 μW from a 1-V power supply and the prototype occupies an active area of 0.12 mm 2 . (semiconductor integrated circuits)

An ELMO2-RhoG-ILK network modulates microtubule dynamics.

Science.gov (United States)

Jackson, Bradley C; Ivanova, Iordanka A; Dagnino, Lina

2015-07-15

ELMO2 belongs to a family of scaffold proteins involved in phagocytosis and cell motility. ELMO2 can simultaneously bind integrin-linked kinase (ILK) and RhoG, forming tripartite ERI complexes. These complexes are involved in promoting β1 integrin-dependent directional migration in undifferentiated epidermal keratinocytes. ELMO2 and ILK have also separately been implicated in microtubule regulation at integrin-containing focal adhesions. During differentiation, epidermal keratinocytes cease to express integrins, but ERI complexes persist. Here we show an integrin-independent role of ERI complexes in modulation of microtubule dynamics in differentiated keratinocytes. Depletion of ERI complexes by inactivating the Ilk gene in these cells reduces microtubule growth and increases the frequency of catastrophe. Reciprocally, exogenous expression of ELMO2 or RhoG stabilizes microtubules, but only if ILK is also present. Mechanistically, activation of Rac1 downstream from ERI complexes mediates their effects on microtubule stability. In this pathway, Rac1 serves as a hub to modulate microtubule dynamics through two different routes: 1) phosphorylation and inactivation of the microtubule-destabilizing protein stathmin and 2) phosphorylation and inactivation of GSK-3β, which leads to the activation of CRMP2, promoting microtubule growth. At the cellular level, the absence of ERI species impairs Ca(2+)-mediated formation of adherens junctions, critical to maintaining mechanical integrity in the epidermis. Our findings support a key role for ERI species in integrin-independent stabilization of the microtubule network in differentiated keratinocytes. © 2015 Jackson 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).

Directional and dynamic modulation of the optical emission of an individual GaAs nanowire using surface acoustic waves.

Science.gov (United States)

Kinzel, Jörg B; Rudolph, Daniel; Bichler, Max; Abstreiter, Gerhard; Finley, Jonathan J; Koblmüller, Gregor; Wixforth, Achim; Krenner, Hubert J

2011-04-13

We report on optical experiments performed on individual GaAs nanowires and the manipulation of their temporal emission characteristics using a surface acoustic wave. We find a pronounced, characteristic suppression of the emission intensity for the surface acoustic wave propagation aligned with the axis of the nanowire. Furthermore, we demonstrate that this quenching is dynamical as it shows a pronounced modulation as the local phase of the surface acoustic wave is tuned. These effects are strongly reduced for a surface acoustic wave applied in the direction perpendicular to the axis of the nanowire due to their inherent one-dimensional geometry. We resolve a fully dynamic modulation of the nanowire emission up to 678 MHz not limited by the physical properties of the nanowires.

Localized nonlinear waves and dynamical stability in spinor Bose–Einstein condensates with time–space modulation

Science.gov (United States)

Yao, Yu-Qin; Han, Wei; Li, Ji; Liu, Wu-Ming

2018-05-01

Nonlinearity is one of the most remarkable characteristics of Bose–Einstein condensates (BECs). Much work has been done on one- and two-component BECs with time- or space-modulated nonlinearities, while there is little work on spinor BECs with space–time-modulated nonlinearities. In the present paper we investigate localized nonlinear waves and dynamical stability in spinor Bose–Einstein condensates with nonlinearities dependent on time and space. We solve the three coupled Gross–Pitaevskii equations by similarity transformation and obtain two families of exact matter wave solutions in terms of Jacobi elliptic functions and the Mathieu equation. The localized states of the spinor matter wave describe the dynamics of vector breathing solitons, moving breathing solitons, quasi-breathing solitons and resonant solitons. The results show that one-order vector breathing solitons, quasi-breathing solitons, resonant solitons and the moving breathing solitons ψ ±1 are all stable, but the moving breathing soliton ψ 0 is unstable. We also present the experimental parameters to realize these phenomena in future experiments.

Enhanced Microgrid Dynamic Performance Using a Modulated Power Filter Based on Enhanced Bacterial Foraging Optimization

Directory of Open Access Journals (Sweden)

Ahmed M. Othman

2017-06-01

Full Text Available This paper presents a design of microgrid (MG with enhanced dynamic performance. Distributed energy resources (DER are widely used in MGs to match the various load types and profiles. DERs include solar PV cells, wind energy sources, fuel cells, batteries, micro gas-engines and storage elements. MG will include AC/DC circuits, developed power electronics devices, inverters and power electronic controllers. A novel modulated power filters (MPF device will be applied in MG design. Enhanced bacterial foraging optimization (EBFO will be proposed to optimize and set the MPF parameters to enhance and tune the MG dynamic response. Recent dynamic control is applied to minimize the harmonic reference content. EBFO will adapt the gains of MPF dynamic control. The present research achieves an enhancement of MG dynamic performance, in addition to ensuring improvements in the power factor, bus voltage profile and power quality. MG operation will be evaluated by the dynamic response to be fine-tuned by MPF based on EBFO. Digital simulations have validated the results to show the effectiveness and efficient improvement by the proposed strategy.

Dynamic nuclear polarization by frequency modulation of a tunable gyrotron of 260GHz.

Science.gov (United States)

Yoon, Dongyoung; Soundararajan, Murari; Cuanillon, Philippe; Braunmueller, Falk; Alberti, Stefano; Ansermet, Jean-Philippe

2016-01-01

An increase in Dynamic Nuclear Polarization (DNP) signal intensity is obtained with a tunable gyrotron producing frequency modulation around 260GHz at power levels less than 1W. The sweep rate of frequency modulation can reach 14kHz, and its amplitude is fixed at 50MHz. In water/glycerol glassy ice doped with 40mM TEMPOL, the relative increase in the DNP enhancement was obtained as a function of frequency-sweep rate for several temperatures. A 68 % increase was obtained at 15K, thus giving a DNP enhancement of about 80. By employing λ/4 and λ/8 polarizer mirrors, we transformed the polarization of the microwave beam from linear to circular, and achieved an increase in the enhancement by a factor of about 66% for a given power. Copyright © 2015 Elsevier Inc. All rights reserved.

Non-thermal atmospheric pressure plasma inhibits thyroid papillary cancer cell invasion via cytoskeletal modulation, altered MMP-2/-9/uPA activity.

Directory of Open Access Journals (Sweden)

Jae Won Chang

Full Text Available Plasma, the fourth state of matter, is defined as a partially or completely ionized gas that includes a mixture of electrons and ions. Advances in plasma physics have made it possible to use non-thermal atmospheric pressure plasma (NTP in cancer research. However, previous studies have focused mainly on apoptotic cancer cell death mediated by NTP as a potential cancer therapy. In this study, we investigated the effect of NTP on invasion or metastasis, as well as the mechanism by which plasma induces anti-migration and anti-invasion properties in human thyroid papillary cancer cell lines (BHP10-3 and TPC1. Wound healing, pull-down, and Transwell assays demonstrated that NTP reduced cell migration and invasion. In addition, NTP induced morphological changes and cytoskeletal rearrangements, as detected by scanning electron microscopy and immunocytochemistry. We also examined matrix metalloproteinase (MMP-2/-9 and urokinase-type plasminogen activator (uPA activity using gelatin zymography, uPA assays and RT-PCR. FAK, Src, and paxillin expression was detected using Western blot analyses and immunocytochemistry. NTP decreased FAK, Src, and paxillin expression as well as MMP/uPA activity. In conclusion, NTP inhibited the invasion and metastasis of BHP10-3 and TPC1 cells by decreasing MMP-2/-9 and uPA activities and rearranging the cytoskeleton, which is regulated by the FAK/Src complex. These findings suggest novel actions for NTP and may aid in the development of new therapeutic strategies for locally invasive and metastatic cancers.

Cytoskeletal actin genes function downstream of HNF-3beta in ascidian notochord development.

Science.gov (United States)

Jeffery, W R; Ewing, N; Machula, J; Olsen, C L; Swalla, B J

1998-11-01

We have examined the expression and regulation of cytoskeletal actin genes in ascidians with tailed (Molgula oculata) and tailless larvae (Molgula occulta). Four cDNA clones were isolated representing two pairs of orthologous cytoskeletal actin genes (CA1 and CA2), which encode proteins differing by five amino acids in the tailed and tailless species. The CA1 and CA2 genes are present in one or two copies, although several related genes may also be present in both species. Maternal CA1 and CA2 mRNA is present in small oocytes but transcript levels later decline, suggesting a role in early oogenesis. In the tailed species, embryonic CA1 and CA2 mRNAs first appear in the presumptive mesenchyme and muscle cells during gastrulation, subsequently accumulate in the presumptive notochord cells, and can be detected in these tissues through the tadpole stage. CA1 mRNAs accumulate initially in the same tissues in the tailless species but subsequently disappear, in concert with the arrest of notochord and tail development. In contrast, CA2 mRNAs were not detected in embryos of the tailless species. Fertilization of eggs of the tailless species with sperm of the tailed species, which restores the notochord and the tail, also results in the upregulation of CA1 and CA2 gene expression in hybrid embryos. Antisense oligodeoxynucleotide experiments suggest that CA1 and CA2 expression in the notochord, but not in the muscle cells, is dependent on prior expression of Mocc FHI, an ascidian HNF-3beta-like gene. The expression of the CA1 and CA2 genes in the notochord in the tailed species, downregulation in the tailless species, upregulation in interspecific hybrids, and dependence on HNF-3beta activity is consistent with a role of these genes in development of the ascidian notochord.

Molecular dynamics simulation of amplitude modulation atomic force microscopy

International Nuclear Information System (INIS)

Hu, Xiaoli; Martini, Ashlie; Egberts, Philip; Dong, Yalin

2015-01-01

Molecular dynamics (MD) simulations were used to model amplitude modulation atomic force microscopy (AM-AFM). In this novel simulation, the model AFM tip responds to both tip–substrate interactions and to a sinusoidal excitation signal. The amplitude and phase shift of the tip oscillation observed in the simulation and their variation with tip–sample distance were found to be consistent with previously reported trends from experiments and theory. These simulation results were also fit to an expression enabling estimation of the energy dissipation, which was found to be smaller than that in a corresponding experiment. The difference was analyzed in terms of the effects of tip size and substrate thickness. Development of this model is the first step toward using MD to gain insight into the atomic-scale phenomena that occur during an AM-AFM measurement. (paper)

THE EFFECT OF A DYNAMIC INNER HELIOSHEATH THICKNESS ON COSMIC-RAY MODULATION

International Nuclear Information System (INIS)

Manuel, R.; Ferreira, S. E. S.; Potgieter, M. S.

2015-01-01

The time-dependent modulation of galactic cosmic rays in the heliosphere is studied over different polarity cycles by computing 2.5 GV proton intensities using a two-dimensional, time-dependent modulation model. By incorporating recent theoretical advances in the relevant transport parameters in the model, we showed in previous work that this approach gave realistic computed intensities over a solar cycle. New in this work is that a time dependence of the solar wind termination shock (TS) position is implemented in our model to study the effect of a dynamic inner heliosheath thickness (the region between the TS and heliopause) on the solar modulation of galactic cosmic rays. The study reveals that changes in the inner heliosheath thickness, arising from a time-dependent shock position, does affect cosmic-ray intensities everywhere in the heliosphere over a solar cycle, with the smallest effect in the innermost heliosphere. A time-dependent TS position causes a phase difference between the solar activity periods and the corresponding intensity periods. The maximum intensities in response to a solar minimum activity period are found to be dependent on the time-dependent TS profile. It is found that changing the width of the inner heliosheath with time over a solar cycle can shift the time of when the maximum or minimum cosmic-ray intensities occur at various distances throughout the heliosphere, but more significantly in the outer heliosphere. The time-dependent extent of the inner heliosheath, as affected by solar activity conditions, is thus an additional time-dependent factor to be considered in the long-term modulation of cosmic rays

Optical Tweezers-Based Measurements of Forces and Dynamics at Microtubule Ends.

Science.gov (United States)

Baclayon, Marian; Kalisch, Svenja-Marei; Hendel, Ed; Laan, Liedewij; Husson, Julien; Munteanu, E Laura; Dogterom, Marileen

2017-01-01

Microtubules are dynamic cytoskeletal polymers that polymerize and depolymerize while interacting with different proteins and structures within the cell. The highly regulated dynamic properties as well as the pushing and pulling forces generated by dynamic microtubule ends play important roles in processes such as in cell division. For instance, microtubule end-binding proteins are known to affect dramatically the dynamic properties of microtubules, and cortical dyneins are known to mediate pulling forces on microtubule ends. We discuss in this chapter our efforts to reconstitute these systems in vitro and mimic their interactions with structures within the cell using micro-fabricated barriers. Using an optical tweezers setup, we investigate the dynamics and forces of microtubules growing against functionalized barriers in the absence and presence of end-binding proteins and barrier-attached motor proteins. This setup allows high-speed as well as nanometer and piconewton resolution measurements on dynamic microtubules.

Reverse micelles as a tool for probing solvent modulation of protein dynamics: Reverse micelle encapsulated hemoglobin

Science.gov (United States)

Roche, Camille J.; Dantsker, David; Heller, Elizabeth R.; Sabat, Joseph E.; Friedman, Joel M.

2013-08-01

Hydration waters impact protein dynamics. Dissecting the interplay between hydration waters and dynamics requires a protein that manifests a broad range of dynamics. Proteins in reverse micelles (RMs) have promise as tools to achieve this objective because the water content can be manipulated. Hemoglobin is an appropriate tool with which to probe hydration effects. We describe both a protocol for hemoglobin encapsulation in reverse micelles and a facile method using PEG and cosolvents to manipulate water content. Hydration properties are probed using the water-sensitive fluorescence from Hb bound pyranine and covalently attached Badan. Protein dynamics are probed through ligand recombination traces derived from photodissociated carbonmonoxy hemoglobin on a log scale that exposes the potential role of both α and β solvent fluctuations in modulating protein dynamics. The results open the possibility of probing hydration level phenomena in this system using a combination of NMR and optical probes.

Estradiol influences the mechanical properties of human fetal osteoblasts through cytoskeletal changes

Energy Technology Data Exchange (ETDEWEB)

Muthukumaran, Padmalosini [Department of Bioengineering, National University of Singapore (Singapore); Lim, Chwee Teck [Department of Bioengineering, National University of Singapore (Singapore); Department of Mechanical Engineering, National University of Singapore (Singapore); Mechanobiology Institute, National University of Singapore (Singapore); Singapore-MIT Alliance for Research and Technology (SMART), National University of Singapore (Singapore); Lee, Taeyong, E-mail: bielt@nus.edu.sg [Department of Bioengineering, National University of Singapore (Singapore)

2012-07-06

Highlights: Black-Right-Pointing-Pointer Estradiol induced stiffness changes of osteoblasts were quantified using AFM. Black-Right-Pointing-Pointer Estradiol causes significant decrease in the stiffness of osteoblasts. Black-Right-Pointing-Pointer Decreased stiffness was caused by decreased density of f-actin network. Black-Right-Pointing-Pointer Stiffness changes were not associated with mineralized matrix of osteoblasts. Black-Right-Pointing-Pointer Estradiol increases inherent alkaline phosphatase activity of osteoblasts. -- Abstract: Estrogen is known to have a direct effect on bone forming osteoblasts and bone resorbing osteoclasts. The cellular and molecular effects of estrogen on osteoblasts and osteoblasts-like cells have been extensively studied. However, the effect of estrogen on the mechanical property of osteoblasts has not been studied yet. It is important since mechanical property of the mechanosensory osteoblasts could be pivotal to its functionality in bone remodeling. This is the first study aimed to assess the direct effect of estradiol on the apparent elastic modulus (E{sup Asterisk-Operator }) and corresponding cytoskeletal changes of human fetal osteoblasts (hFOB 1.19). The cells were cultured in either medium alone or medium supplemented with {beta}-estradiol and then subjected to Atomic Force Microscopy indentation (AFM) to determine E{sup Asterisk-Operator }. The underlying changes in cytoskeleton were studied by staining the cells with TRITC-Phalloidin. Following estradiol treatment, the cells were also tested for proliferation, alkaline phosphatase activity and mineralization. With estradiol treatment, E{sup Asterisk-Operator} of osteoblasts significantly decreased by 43-46%. The confocal images showed that the changes in f-actin network observed in estradiol treated cells can give rise to the changes in the stiffness of the cells. Estradiol also increases the inherent alkaline phosphatase activity of the cells. Estradiol induced stiffness

Estradiol influences the mechanical properties of human fetal osteoblasts through cytoskeletal changes

International Nuclear Information System (INIS)

Muthukumaran, Padmalosini; Lim, Chwee Teck; Lee, Taeyong

2012-01-01

Highlights: ► Estradiol induced stiffness changes of osteoblasts were quantified using AFM. ► Estradiol causes significant decrease in the stiffness of osteoblasts. ► Decreased stiffness was caused by decreased density of f-actin network. ► Stiffness changes were not associated with mineralized matrix of osteoblasts. ► Estradiol increases inherent alkaline phosphatase activity of osteoblasts. -- Abstract: Estrogen is known to have a direct effect on bone forming osteoblasts and bone resorbing osteoclasts. The cellular and molecular effects of estrogen on osteoblasts and osteoblasts-like cells have been extensively studied. However, the effect of estrogen on the mechanical property of osteoblasts has not been studied yet. It is important since mechanical property of the mechanosensory osteoblasts could be pivotal to its functionality in bone remodeling. This is the first study aimed to assess the direct effect of estradiol on the apparent elastic modulus (E ∗ ) and corresponding cytoskeletal changes of human fetal osteoblasts (hFOB 1.19). The cells were cultured in either medium alone or medium supplemented with β-estradiol and then subjected to Atomic Force Microscopy indentation (AFM) to determine E ∗ . The underlying changes in cytoskeleton were studied by staining the cells with TRITC-Phalloidin. Following estradiol treatment, the cells were also tested for proliferation, alkaline phosphatase activity and mineralization. With estradiol treatment, E ∗ of osteoblasts significantly decreased by 43–46%. The confocal images showed that the changes in f-actin network observed in estradiol treated cells can give rise to the changes in the stiffness of the cells. Estradiol also increases the inherent alkaline phosphatase activity of the cells. Estradiol induced stiffness changes of osteoblasts were not associated with changes in the synthesized mineralized matrix of the cells. Thus, a decrease in osteoblast stiffness with estrogen treatment was

Multi-dimensional modulations of alpha and gamma cortical dynamics following mindfulness-based cognitive therapy in Major Depressive Disorder

NARCIS (Netherlands)

Schoenberg, P.L.; Speckens, A.E.M.

2015-01-01

To illuminate candidate neural working mechanisms of Mindfulness-Based Cognitive Therapy (MBCT) in the treatment of recurrent depressive disorder, parallel to the potential interplays between modulations in electro-cortical dynamics and depressive symptom severity and self-compassionate experience.

A design of optical modulation system with pixel-level modulation accuracy

Science.gov (United States)

Zheng, Shiwei; Qu, Xinghua; Feng, Wei; Liang, Baoqiu

2018-01-01

Vision measurement has been widely used in the field of dimensional measurement and surface metrology. However, traditional methods of vision measurement have many limits such as low dynamic range and poor reconfigurability. The optical modulation system before image formation has the advantage of high dynamic range, high accuracy and more flexibility, and the modulation accuracy is the key parameter which determines the accuracy and effectiveness of optical modulation system. In this paper, an optical modulation system with pixel level accuracy is designed and built based on multi-points reflective imaging theory and digital micromirror device (DMD). The system consisted of digital micromirror device, CCD camera and lens. Firstly we achieved accurate pixel-to-pixel correspondence between the DMD mirrors and the CCD pixels by moire fringe and an image processing of sampling and interpolation. Then we built three coordinate systems and calculated the mathematic relationship between the coordinate of digital micro-mirror and CCD pixels using a checkerboard pattern. A verification experiment proves that the correspondence error is less than 0.5 pixel. The results show that the modulation accuracy of system meets the requirements of modulation. Furthermore, the high reflecting edge of a metal circular piece can be detected using the system, which proves the effectiveness of the optical modulation system.

An electrically driven terahertz metamaterial diffractive modulator with more than 20 dB of dynamic range

International Nuclear Information System (INIS)

Karl, N.; Reichel, K.; Mendis, R.; Mittleman, D. M.; Chen, H.-T.; Taylor, A. J.; Brener, I.; Benz, A.; Reno, J. L.

2014-01-01

We design and experimentally demonstrate a switchable diffraction grating for terahertz modulation based on planar active metamaterials, where a Schottky gate structure is implemented to tune the metamaterial resonances in real-time via the application of an external voltage bias. The diffraction grating is formed by grouping the active split-ring resonators into an array of independent columns with alternate columns biased. We observe off-axis diffraction over a wide frequency band in contrast to the narrow-band resonances, which permits operation of the device as a relatively high-speed, wide-bandwidth, high-contrast modulator, with more than 20 dB of dynamic range

Modulational effects in accelerators

International Nuclear Information System (INIS)

Satogata, T.

1997-01-01

We discuss effects of field modulations in accelerators, specifically those that can be used for operational beam diagnostics and beam halo control. In transverse beam dynamics, combined effects of nonlinear resonances and tune modulations influence diffusion rates with applied tune modulation has been demonstrated. In the longitudinal domain, applied RF phase and voltage modulations provide mechanisms for parasitic halo transport, useful in slow crystal extraction. Experimental experiences with transverse tune and RF modulations are also discussed

Damping Effects of Drogue Parachutes on Orion Crew Module Dynamics

Science.gov (United States)

Aubuchon, Vanessa V.; Owens, D. Bruce

2016-01-01

Because simulations of the Orion Crew Module (CM) dynamics with drogue parachutes deployed were under-predicting the amount of damping seen in free-flight tests, an attach-point damping model was applied to the Orion system. A key hypothesis in this model is that the drogue parachutes' net load vector aligns with the CM drogue attachment point velocity vector. This assumption seems reasonable and has historically produced good results, but has never been experimentally verified. The wake of the CM influences the drogue parachutes, which makes performance predictions of the parachutes difficult. Many of these effects are not currently modeled in the simulations. A forced oscillation test of the CM with parachutes was conducted in the NASA LaRC 20-Ft Vertical Spin Tunnel (VST) to gather additional data to validate and refine the attach-point damping model. A second loads balance was added to the original Orion VST model to measure the drogue parachute loads independently of the CM. The objective of the test was to identify the contribution of the drogues to CM damping and provide additional information to quantify wake effects and the interactions between the CM and parachutes. The drogue parachute force vector was shown to be highly dependent on the CM wake characteristics. Based on these wind tunnel test data, the attach-point damping model was determined to be a sufficient approximation of the parachute dynamics in relationship to the CM dynamics for preliminary entry vehicle system design. More wake effects should be included to better model the system.

The dosimetric impact of inversely optimized arc radiotherapy plan modulation for real-time dynamic MLC tracking delivery

DEFF Research Database (Denmark)

Falk, Marianne; Larsson, Tobias; Keall, P.

2012-01-01

Purpose: Real-time dynamic multileaf collimator (MLC) tracking for management of intrafraction tumor motion can be challenging for highly modulated beams, as the leaves need to travel far to adjust for target motion perpendicular to the leaf travel direction. The plan modulation can be reduced......-to-peak displacement of 2 cm and a cycle time of 6 s. The delivery was adjusted to the target motion using MLC tracking, guided in real-time by an infrared optical system. The dosimetric results were evaluated using gamma index evaluation with static target measurements as reference. Results: The plan quality...

Why is cytoskeletal contraction required for cardiac fusion before but not after looping begins?

Science.gov (United States)

Shi, Yunfei; Varner, Victor D.; Taber, Larry A.

2015-02-01

Cytoskeletal contraction is crucial to numerous morphogenetic processes, but its role in early heart development is poorly understood. Studies in chick embryos have shown that inhibiting myosin-II-based contraction prior to Hamburger-Hamilton (HH) stage 10 (33 h incubation) impedes fusion of the mesodermal heart fields that create the primitive heart tube (HT), as well as the ensuing process of cardiac looping. If contraction is inhibited at or after looping begins at HH10, however, fusion and looping proceed relatively normally. To explore the mechanisms behind this seemingly fundamental change in behavior, we measured spatiotemporal distributions of tissue stiffness, stress, and strain around the anterior intestinal portal (AIP), the opening to the foregut where contraction and cardiac fusion occur. The results indicate that stiffness and tangential tension decreased bilaterally along the AIP with distance from the embryonic midline. The gradients in stiffness and tension, as well as strain rate, increased to peaks at HH9 (30 h) and decreased afterward. Exposure to the myosin II inhibitor blebbistatin reduced these effects, suggesting that they are mainly generated by active cytoskeletal contraction, and finite-element modeling indicates that the measured mechanical gradients are consistent with a relatively uniform contraction of the endodermal layer in conjunction with constraints imposed by the attached mesoderm. Taken together, our results suggest that, before HH10, endodermal contraction pulls the bilateral heart fields toward the midline where they fuse to create the HT. By HH10, however, the fusion process is far enough along to enable apposing cardiac progenitor cells to keep ‘zipping’ together during looping without the need for continued high contractile forces. These findings should shed new light on a perplexing question in early heart development.

Why is cytoskeletal contraction required for cardiac fusion before but not after looping begins?

International Nuclear Information System (INIS)

Shi, Yunfei; Taber, Larry A; Varner, Victor D

2015-01-01

Cytoskeletal contraction is crucial to numerous morphogenetic processes, but its role in early heart development is poorly understood. Studies in chick embryos have shown that inhibiting myosin-II-based contraction prior to Hamburger–Hamilton (HH) stage 10 (33 h incubation) impedes fusion of the mesodermal heart fields that create the primitive heart tube (HT), as well as the ensuing process of cardiac looping. If contraction is inhibited at or after looping begins at HH10, however, fusion and looping proceed relatively normally. To explore the mechanisms behind this seemingly fundamental change in behavior, we measured spatiotemporal distributions of tissue stiffness, stress, and strain around the anterior intestinal portal (AIP), the opening to the foregut where contraction and cardiac fusion occur. The results indicate that stiffness and tangential tension decreased bilaterally along the AIP with distance from the embryonic midline. The gradients in stiffness and tension, as well as strain rate, increased to peaks at HH9 (30 h) and decreased afterward. Exposure to the myosin II inhibitor blebbistatin reduced these effects, suggesting that they are mainly generated by active cytoskeletal contraction, and finite-element modeling indicates that the measured mechanical gradients are consistent with a relatively uniform contraction of the endodermal layer in conjunction with constraints imposed by the attached mesoderm. Taken together, our results suggest that, before HH10, endodermal contraction pulls the bilateral heart fields toward the midline where they fuse to create the HT. By HH10, however, the fusion process is far enough along to enable apposing cardiac progenitor cells to keep ‘zipping’ together during looping without the need for continued high contractile forces. These findings should shed new light on a perplexing question in early heart development. (paper)

Relaxation Dynamics of the Glass Transition in PMMA+SWCNT Composites by Temperature-Modulated DSC

Science.gov (United States)

Pradhan, Nihar; Iannacchione, Germano

2010-03-01

Temperature Modulated Differential Scanning Calorimeter (TMDSC) used to investigate the thermal relaxation dynamics of PMMA-Single wall carbon nanotubes (SWCNTs) through the glass transition as a function of frequency. A strong dependence of the temperature dependence peak in imaginary part of complex heat capacity (Tmax) was found during the transition from glass like to liquid like region and can be described by Arhenius law. The activation energy shows increases while the charactersistic time decreases with increasing mass fraction (φm) of SWCNTs. Decreasing of enthalpy, while heating and slowly increasing while cooling at 2.0 K/min scan rate was observed and as frequency of temperature modulation increases. There is no relative change of enthalpy in heating and cooling observed at sufficiently slow scan rate. The glass transition temperature (Tg) shows increases as a function of frequency of temperature modulation, φm of SWCNTs and with increasing scan rate. From imaginary part of heat capacity, it obvious that Tmax is not the actual glass transition temperature of pure polymer but Tmax and Tg values can be superimpose when φm of SWCNT increases in polymer.

Observation Platform for Dynamic Biomedical and Biotechnology Experiments Using the International Space Station (ISS) Light Microscopy Module (LMM)

Science.gov (United States)

Kurk, Michael A. (Andy)

2015-01-01

Techshot, Inc., has developed an observation platform for the LMM on the ISS that will enable biomedical and biotechnology experiments. The LMM Dynamic Stage consists of an electronics module and the first two of a planned suite of experiment modules. Specimens and reagent solutions can be injected into a small, hollow microscope slide-the heart of the innovation-via a combination of small reservoirs, pumps, and valves. A life science experiment module allows investigators to load up to two different fluids for on-orbit, real-time image cytometry. Fluids can be changed to initiate a process, fix biological samples, or retrieve suspended cells. A colloid science experiment module conducts microparticle and nanoparticle tests for investigation of colloid self-assembly phenomena. This module includes a hollow glass slide and heating elements for the creation of a thermal gradient from one end of the slide to the other. The electronics module supports both experiment modules and contains a unique illuminator/condenser for bright and dark field and phase contrast illumination, power supplies for two piezoelectric pumps, and controller boards for pumps and valves. This observation platform safely contains internal fluids and will greatly accelerate the research and development (R&D) cycle of numerous experiments, products, and services aboard the ISS.

The Stereociliary Paracrystal Is a Dynamic Cytoskeletal Scaffold In Vivo

Directory of Open Access Journals (Sweden)

Philsang Hwang

2015-11-01

Full Text Available Permanency of mechanosensory stereocilia may be the consequence of low protein turnover or rapid protein renewal. Here, we devise a system, using optical techniques in live zebrafish, to distinguish between these mechanisms. We demonstrate that the stereocilium’s abundant actin cross-linker fascin 2b exchanges, without bias or a phosphointermediate, orders of magnitude faster (t1/2 of 76.3 s than any other known hair bundle protein. To establish the logic of fascin 2b’s exchange, we examine whether filamentous actin is dynamic and detect substantial β-actin exchange within the stereocilium’s paracrystal (t1/2 of 4.08 hr. We propose that fascin 2b’s behavior may enable cross-linking at fast timescales of stereocilia vibration while noninstructively facilitating the slower process of actin exchange. Furthermore, tip protein myosin XVa fully exchanges in hours (t1/2 of 11.6 hr, indicating that delivery of myosin-associated cargo occurs in mature stereocilia. These findings suggest that stereocilia permanency is underpinned by vibrant protein exchange.

Espins are multifunctional actin cytoskeletal regulatory proteins in the microvilli of chemosensory and mechanosensory cells

Science.gov (United States)

Sekerková, Gabriella; Zheng, Lili; Loomis, Patricia A.; Changyaleket, Benjarat; Whitlon, Donna S.; Mugnaini, Enrico; Bartles, James R.

2010-01-01

Espins are associated with the parallel actin bundles of hair cell stereocilia and are the target of mutations that cause deafness and vestibular dysfunction in mice and humans. Here, we report that espins are also concentrated in the microvilli of a number of other sensory cells: vomeronasal organ sensory neurons, solitary chemoreceptor cells, taste cells and Merkel cells. Moreover, we show that hair cells and these other sensory cells contain novel espin isoforms that arise from a different transcriptional start site and differ significantly from other espin isoforms in their complement of ligand-binding activities and their effects on actin polymerization. The novel espin isoforms of sensory cells bundled actin filaments with high affinity in a Ca2+-resistant fashion, bound actin monomer via a WASP homology 2 domain, bound profilin via a single proline-rich peptide, and caused a dramatic elongation of microvillus-type parallel actin bundles in transfected epithelial cells. In addition, the novel espin isoforms of sensory cells differed from other espin isoforms in that they potently inhibited actin polymerization in vitro, did not bind the Src homology 3 domain of the adapter protein insulin receptor substrate p53 and did not bind the acidic, signaling phospholipid phosphatidylinositol 4,5- bisphosphate. Thus, the espins constitute a family of multifunctional actin cytoskeletal regulatory proteins with the potential to differentially influence the organization, dimensions, dynamics and signaling capabilities of the actin filament-rich, microvillus-type specializations that mediate sensory transduction in a variety of mechanosensory and chemosensory cells. PMID:15190118

Quinolinic acid induces disrupts cytoskeletal homeostasis in striatal neurons. Protective role of astrocyte-neuron interaction.

Science.gov (United States)

Pierozan, Paula; Ferreira, Fernanda; de Lima, Bárbara Ortiz; Pessoa-Pureur, Regina

2015-02-01

Quinolinic acid (QUIN) is an endogenous metabolite of the kynurenine pathway involved in several neurological disorders. Among the several mechanisms involved in QUIN-mediated toxicity, disruption of the cytoskeleton has been demonstrated in striatally injected rats and in striatal slices. The present work searched for the actions of QUIN in primary striatal neurons. Neurons exposed to 10 µM QUIN presented hyperphosphorylated neurofilament (NF) subunits (NFL, NFM, and NFH). Hyperphosphorylation was abrogated in the presence of protein kinase A and protein kinase C inhibitors H89 (20 μM) and staurosporine (10 nM), respectively, as well as by specific antagonists to N-methyl-D-aspartate (50 µM DL-AP5) and metabotropic glutamate receptor 1 (100 µM MPEP). Also, intra- and extracellular Ca(2+) chelators (10 µM BAPTA-AM and 1 mM EGTA, respectively) and Ca(2+) influx through L-type voltage-dependent Ca(2+) channel (10 µM verapamil) are implicated in QUIN-mediated effects. Cells immunostained for the neuronal markers βIII-tubulin and microtubule-associated protein 2 showed altered neurite/neuron ratios and neurite outgrowth. NF hyperphosphorylation and morphological alterations were totally prevented by conditioned medium from QUIN-treated astrocytes. Cocultured astrocytes and neurons interacted with one another reciprocally, protecting them against QUIN injury. Cocultured cells preserved their cytoskeletal organization and cell morphology together with unaltered activity of the phosphorylating system associated with the cytoskeleton. This article describes cytoskeletal disruption as one of the most relevant actions of QUIN toxicity in striatal neurons in culture with soluble factors secreted by astrocytes, with neuron-astrocyte interaction playing a role in neuroprotection. © 2014 Wiley Periodicals, Inc.

Correlative STED and Atomic Force Microscopy on Live Astrocytes Reveals Plasticity of Cytoskeletal Structure and Membrane Physical Properties during Polarized Migration

Directory of Open Access Journals (Sweden)

Nathalie Rouach

2017-04-01

Full Text Available The plasticity of the cytoskeleton architecture and membrane properties is important for the establishment of cell polarity, adhesion and migration. Here, we present a method which combines stimulated emission depletion (STED super-resolution imaging and atomic force microscopy (AFM to correlate cytoskeletal structural information with membrane physical properties in live astrocytes. Using STED compatible dyes for live cell imaging of the cytoskeleton, and simultaneously mapping the cell surface topology with AFM, we obtain unprecedented detail of highly organized networks of actin and microtubules in astrocytes. Combining mechanical data from AFM with optical imaging of actin and tubulin further reveals links between cytoskeleton organization and membrane properties. Using this methodology we illustrate that scratch-induced migration induces cytoskeleton remodeling. The latter is caused by a polarization of actin and microtubule elements within astroglial cell processes, which correlates strongly with changes in cell stiffness. The method opens new avenues for the dynamic probing of the membrane structural and functional plasticity of living brain cells. It is a powerful tool for providing new insights into mechanisms of cell structural remodeling during physiological or pathological processes, such as brain development or tumorigenesis.

Quasi-periodic dynamics in system with multilevel pulse modulated control

Science.gov (United States)

Gol'tsov, Yu A.; Kizhuk, A. S.; Rubanov, V. G.

2018-03-01

In this paper, the authors describe the transitions from the regular periodic mode to quasiperiodicity that can be observed in a multilevel pulse-width modulated control system for a high-power heating unit. The behavior of such system can be described by a set of two coupled non-autonomous differential equations with discontinuous right-hand sides. The authors reduce the investigation of this system to the studying of a two-dimensional piecewise-smooth map. The authors demonstrate how a closed invariant curve associated with quasiperiodic dynamics can arise from a stable periodic motion through a border-collision bifurcation. The paper also considers a variety of interesting nonlinear phenomena, including phase-locking modes, the coexistence of several stable closed invariant curves, embedded one into the other and with their basins of attraction separated by intervening repelling closed curves.

The effect of the cytoskeletal inhibitors on the splenic lymphocyte traffic and homing in rats

International Nuclear Information System (INIS)

Yang Huibin

1989-01-01

The rat splenic lymphocyte traffic and homing in vivo and the effect of cytoskeletal inhibitors on this process were investigated using the technique of γ-counting of 51 Cr-labelled lymphocytes. The results suggests that:(1) After 2 of intravenous injection, the 51 Cr-labelled lymphocytes from donor rat spleen mainly home to recipient rat spleen, liver, lungs, mesenteric lymph modes (MLN) and gut-associated lymphoid tissues. (2) A significant inhibiting effect on the ability of preferential homing of splenic lymphocytes treated with sodium azide, cytochalasin B or colchicine shows that microtubles and microfilaments play an important role in the lymphocyte traffic and homing

Requirements for a Dynamic Solvent Extraction Module to Support Development of Advanced Technologies for the Recycle of Used Nuclear Fuel

International Nuclear Information System (INIS)

Law, Jack; Rutledge, Veronica; Pereira, Candido; Copple, Jackie; Frey, Kurt; Krebs, John; Maggos, Laura; Nichols, Kevin; Wardle, Kent; Sadasivan, Pratap; DeAlmieda, Valmor; Depaoli, David

2011-01-01

The Department of Energy's Nuclear Energy Advanced Modeling and Simulation (NEAMS) Program has been established to create and deploy next generation, verified and validated nuclear energy modeling and simulation capabilities for the design, implementation, and operation of future nuclear energy systems to improve the U.S. energy security. As part of the NEAMS program, Integrated Performance and Safety Codes (IPSC's) are being produced to significantly advance the status of modeling and simulation of energy systems beyond what is currently available to the extent that the new codes be readily functional in the short term and extensible in the longer term. The four IPSC areas include Safeguards and Separations, Reactors, Fuels, and Waste Forms. As part of the Safeguards and Separations (SafeSeps) IPSC effort, interoperable process models are being developed that enable dynamic simulation of an advanced separations plant. A SafeSepss IPSC 'toolkit' is in development to enable the integration of separation process modules and safeguards tools into the design process by providing an environment to compose, verify and validate a simulation application to be used for analysis of various plant configurations and operating conditions. The modules of this toolkit will be implemented on a modern, expandable architecture with the flexibility to explore and evaluate a wide range of process options while preserving their stand-alone usability. Modules implemented at the plant-level will initially incorporate relatively simple representations for each process through a reduced modeling approach. Final versions will incorporate the capability to bridge to subscale models to provide required fidelity in chemical and physical processes. A dynamic solvent extraction model and its module implementation are needed to support the development of this integrated plant model. As a stand-alone application, it will also support solvent development of extraction flowsheets and integrated

Force Factor Modulation in Electro Dynamic Loudspeakers

DEFF Research Database (Denmark)

Risbo, Lars; Agerkvist, Finn T.; Tinggaard, Carsten

2016-01-01

The relationship between the non-linear phenomenon of ’reluctance force’ and the position dependency of the voice coil inductance was established in 1949 by Cunningham, who called it ’magnetic attraction force’. This paper revisits Cunningham’s analysis and expands it into a generalised form...... that includes the frequency dependency and applies to coils with non-inductive (lossy) blocked impedance. The paper also demonstrates that Cunningham’s force can be explained physically as a modulation of the force factor which again is directly linked to modulation of the flux of the coil. A verification based...... on both experiments and simulations is presented along discussions of the impact of force factor modulation for various motor topologies. Finally, it is shown that the popular L2R2 coil impedance model does not correctly predict the force unless the new analysis is applied....

The bacterial actin MreB rotates, and rotation depends on cell-wall assembly.

Science.gov (United States)

van Teeffelen, Sven; Wang, Siyuan; Furchtgott, Leon; Huang, Kerwyn Casey; Wingreen, Ned S; Shaevitz, Joshua W; Gitai, Zemer

2011-09-20

Bacterial cells possess multiple cytoskeletal proteins involved in a wide range of cellular processes. These cytoskeletal proteins are dynamic, but the driving forces and cellular functions of these dynamics remain poorly understood. Eukaryotic cytoskeletal dynamics are often driven by motor proteins, but in bacteria no motors that drive cytoskeletal motion have been identified to date. Here, we quantitatively study the dynamics of the Escherichia coli actin homolog MreB, which is essential for the maintenance of rod-like cell shape in bacteria. We find that MreB rotates around the long axis of the cell in a persistent manner. Whereas previous studies have suggested that MreB dynamics are driven by its own polymerization, we show that MreB rotation does not depend on its own polymerization but rather requires the assembly of the peptidoglycan cell wall. The cell-wall synthesis machinery thus either constitutes a novel type of extracellular motor that exerts force on cytoplasmic MreB, or is indirectly required for an as-yet-unidentified motor. Biophysical simulations suggest that one function of MreB rotation is to ensure a uniform distribution of new peptidoglycan insertion sites, a necessary condition to maintain rod shape during growth. These findings both broaden the view of cytoskeletal motors and deepen our understanding of the physical basis of bacterial morphogenesis.

High-frequency microrheology reveals cytoskeleton dynamics in living cells

Science.gov (United States)

Rigato, Annafrancesca; Miyagi, Atsushi; Scheuring, Simon; Rico, Felix

2017-08-01

Living cells are viscoelastic materials, dominated by an elastic response on timescales longer than a millisecond. On shorter timescales, the dynamics of individual cytoskeleton filaments are expected to emerge, but active microrheology measurements on cells accessing this regime are scarce. Here, we develop high-frequency microrheology experiments to probe the viscoelastic response of living cells from 1 Hz to 100 kHz. We report the viscoelasticity of different cell types under cytoskeletal drug treatments. On previously inaccessible short timescales, cells exhibit rich viscoelastic responses that depend on the state of the cytoskeleton. Benign and malignant cancer cells revealed remarkably different scaling laws at high frequencies, providing a unique mechanical fingerprint. Microrheology over a wide dynamic range--up to the frequency characterizing the molecular components--provides a mechanistic understanding of cell mechanics.

Level-one modules library for DSNP: Dynamic Simulator for Nuclear Power-plants

International Nuclear Information System (INIS)

Saphier, D.

1978-09-01

The Dynamic Simulator for Nuclear Power-plants (DSNP) is a system of programs and data sets by which a nuclear power plant or part thereof can be simulated at different levels of sophistication. The acronym DSNP is used interchangeably for the DSNP language, for the DSNP precompiler, for the DSNP libraries, and for the DSNP document generator. The DSNP language is a set of simple block oriented statements, which together with the appropriate data, comprise a simulation of a nuclear power plant. The majority of the DSNP statements will result in the inclusion of a simulated physical module into the program. FORTRAN statements can be inserted with no restrictions among DSNP statements

Scaling of F-actin network rheology to probe single filament elasticity and dynamics.

Science.gov (United States)

Gardel, M L; Shin, J H; MacKintosh, F C; Mahadevan, L; Matsudaira, P A; Weitz, D A

2004-10-29

The linear and nonlinear viscoelastic response of networks of cross-linked and bundled cytoskeletal filaments demonstrates remarkable scaling with both frequency and applied prestress, which helps elucidate the origins of the viscoelasticity. The frequency dependence of the shear modulus reflects the underlying single-filament relaxation dynamics for 0.1-10 rad/sec. Moreover, the nonlinear strain stiffening of such networks exhibits a universal form as a function of prestress; this is quantitatively explained by the full force-extension relation of single semiflexible filaments.

Analytical formulation for modulation of time-resolved dynamical Franz-Keldysh effect by electron excitation in dielectrics

Science.gov (United States)

Otobe, T.

2017-12-01

Analytical formulation of subcycle modulation (SCM) of dielectrics including electron excitation is presented. The SCM is sensitive to not only the time-resolved dynamical Franz-Keldysh effect (Tr-DFKE) [T. Otobe et al., Phys. Rev. B 93, 045124 (2016), 10.1103/PhysRevB.93.045124], which is the nonlinear response without the electron excitation, but also the excited electrons. The excited electrons enhance the modulation with even harmonics of pump laser frequency, and generate the odd-harmonics components. The new aspect of SCM is a consequence of (i) the interference between the electrons excited by the pump laser and those excited by the probe-pulse laser and (ii) oscillation of the generated wave packed by the pump laser. When the probe- and pump-pulse polarizations are parallel, the enhancement of the even harmonics and the generation of the odd-harmonics modulation appear. However, if the polarizations are orthogonal, the effect arising from the electron excitations becomes weak. By comparing the parabolic and cosine band models, I found that the electrons under the intense laser field move as quasifree particles.

Path-length-resolved measurements of multiple scattered photons in static and dynamic turbid media using phase-modulated low-coherence interferometry

NARCIS (Netherlands)

Varghese, Babu; Rajan, Vinayakrishnan; van Leeuwen, Ton G.; Steenbergen, Wiendelt

2007-01-01

In optical Doppler measurements, the path length of the light is unknown. To facilitate quantitative measurements, we develop a phase-modulated Mach-Zehnder interferometer with separate fibers for illumination and detection. With this setup, path-length-resolved dynamic light scattering measurements

Broken detailed balance and non-equilibrium dynamics in living systems: a review

Science.gov (United States)

Gnesotto, F. S.; Mura, F.; Gladrow, J.; Broedersz, C. P.

2018-06-01

Living systems operate far from thermodynamic equilibrium. Enzymatic activity can induce broken detailed balance at the molecular scale. This molecular scale breaking of detailed balance is crucial to achieve biological functions such as high-fidelity transcription and translation, sensing, adaptation, biochemical patterning, and force generation. While biological systems such as motor enzymes violate detailed balance at the molecular scale, it remains unclear how non-equilibrium dynamics manifests at the mesoscale in systems that are driven through the collective activity of many motors. Indeed, in several cellular systems the presence of non-equilibrium dynamics is not always evident at large scales. For example, in the cytoskeleton or in chromosomes one can observe stationary stochastic processes that appear at first glance thermally driven. This raises the question how non-equilibrium fluctuations can be discerned from thermal noise. We discuss approaches that have recently been developed to address this question, including methods based on measuring the extent to which the system violates the fluctuation-dissipation theorem. We also review applications of this approach to reconstituted cytoskeletal networks, the cytoplasm of living cells, and cell membranes. Furthermore, we discuss a more recent approach to detect actively driven dynamics, which is based on inferring broken detailed balance. This constitutes a non-invasive method that uses time-lapse microscopy data, and can be applied to a broad range of systems in cells and tissue. We discuss the ideas underlying this method and its application to several examples including flagella, primary cilia, and cytoskeletal networks. Finally, we briefly discuss recent developments in stochastic thermodynamics and non-equilibrium statistical mechanics, which offer new perspectives to understand the physics of living systems.

Broken detailed balance and non-equilibrium dynamics in living systems: a review.

Science.gov (United States)

Gnesotto, F S; Mura, F; Gladrow, J; Broedersz, C P

2018-03-05

Living systems operate far from thermodynamic equilibrium. Enzymatic activity can induce broken detailed balance at the molecular scale. This molecular scale breaking of detailed balance is crucial to achieve biological functions such as high-fidelity transcription and translation, sensing, adaptation, biochemical patterning, and force generation. While biological systems such as motor enzymes violate detailed balance at the molecular scale, it remains unclear how non-equilibrium dynamics manifests at the mesoscale in systems that are driven through the collective activity of many motors. Indeed, in several cellular systems the presence of non-equilibrium dynamics is not always evident at large scales. For example, in the cytoskeleton or in chromosomes one can observe stationary stochastic processes that appear at first glance thermally driven. This raises the question how non-equilibrium fluctuations can be discerned from thermal noise. We discuss approaches that have recently been developed to address this question, including methods based on measuring the extent to which the system violates the fluctuation-dissipation theorem. We also review applications of this approach to reconstituted cytoskeletal networks, the cytoplasm of living cells, and cell membranes. Furthermore, we discuss a more recent approach to detect actively driven dynamics, which is based on inferring broken detailed balance. This constitutes a non-invasive method that uses time-lapse microscopy data, and can be applied to a broad range of systems in cells and tissue. We discuss the ideas underlying this method and its application to several examples including flagella, primary cilia, and cytoskeletal networks. Finally, we briefly discuss recent developments in stochastic thermodynamics and non-equilibrium statistical mechanics, which offer new perspectives to understand the physics of living systems.

Cytoskeletal Linker Protein Dystonin Is Not Critical to Terminal Oligodendrocyte Differentiation or CNS Myelination.

Directory of Open Access Journals (Sweden)

Samantha F Kornfeld

Full Text Available Oligodendrocyte differentiation and central nervous system myelination require massive reorganization of the oligodendrocyte cytoskeleton. Loss of specific actin- and tubulin-organizing factors can lead to impaired morphological and/or molecular differentiation of oligodendrocytes, resulting in a subsequent loss of myelination. Dystonin is a cytoskeletal linker protein with both actin- and tubulin-binding domains. Loss of function of this protein results in a sensory neuropathy called Hereditary Sensory Autonomic Neuropathy VI in humans and dystonia musculorum in mice. This disease presents with severe ataxia, dystonic muscle and is ultimately fatal early in life. While loss of the neuronal isoforms of dystonin primarily leads to sensory neuron degeneration, it has also been shown that peripheral myelination is compromised due to intrinsic Schwann cell differentiation abnormalities. The role of this cytoskeletal linker in oligodendrocytes, however, remains unclear. We sought to determine the effects of the loss of neuronal dystonin on oligodendrocyte differentiation and central myelination. To address this, primary oligodendrocytes were isolated from a severe model of dystonia musculorum, Dstdt-27J, and assessed for morphological and molecular differentiation capacity. No defects could be discerned in the differentiation of Dstdt-27J oligodendrocytes relative to oligodendrocytes from wild-type littermates. Survival was also compared between Dstdt-27J and wild-type oligodendrocytes, revealing no significant difference. Using a recently developed migration assay, we further analysed the ability of primary oligodendrocyte progenitor cell motility, and found that Dstdt-27J oligodendrocyte progenitor cells were able to migrate normally. Finally, in vivo analysis of oligodendrocyte myelination was done in phenotype-stage optic nerve, cerebral cortex and spinal cord. The density of myelinated axons and g-ratios of Dstdt-27J optic nerves was normal, as

Longitudinal density modulation and energy conversion in intense beams

International Nuclear Information System (INIS)

Harris, J. R.; Neumann, J. G.; Tian, K.; O'Shea, P. G.

2007-01-01

Density modulation of charged particle beams may occur as a consequence of deliberate action, or may occur inadvertently because of imperfections in the particle source or acceleration method. In the case of intense beams, where space charge and external focusing govern the beam dynamics, density modulation may, under some circumstances, be converted to velocity modulation, with a corresponding conversion of potential energy to kinetic energy. Whether this will occur depends on the properties of the beam and the initial modulation. This paper describes the evolution of discrete and continuous density modulations on intense beams and discusses three recent experiments related to the dynamics of density-modulated electron beams

Direct current stimulation of the left temporoparietal junction modulates dynamic humor appreciation.

Science.gov (United States)

Slaby, Isabella; Holmes, Amanda; Moran, Joseph M; Eddy, Marianna D; Mahoney, Caroline R; Taylor, Holly A; Brunyé, Tad T

2015-11-11

The aim of this study was to evaluate the influence of transcranial direct current stimulation targeting the left temporoparietal junction (TPJ) on humor appreciation during a dynamic video rating task. In a within-participants design, we targeted the left TPJ with anodal, cathodal, or no transcranial direct current stimulation, centered at electrode site C3 using a 4×1 targeted stimulation montage. During stimulation, participants dynamically rated a series of six stand-up comedy videos for perceived humor. We measured event-related (time-locked to crowd laughter) modulation of humor ratings as a function of stimulation condition. Results showed decreases in rated humor during anodal (vs. cathodal or none) stimulation; this pattern was evident for the majority of videos and was only partially predicted by individual differences in humor style. We discuss the possibility that upregulation of neural circuits involved in the theory of mind and empathizing with others may reduce appreciation of aggressive humor. In conclusion, the present data show that neuromodulation of the TPJ can alter the mental processes underlying humor appreciation, suggesting critical involvement of this cortical region in detecting, comprehending, and appreciating humor.

Dynamic and quasi-dynamic multileaf collimation

International Nuclear Information System (INIS)

Bortfeld, T.

1995-01-01

Several recent investigations deal with the problem of how to produce arbitrary two-dimensional x-ray fluence distributions by means of a multileaf collimator (MLC), an approach, which could be called multileaf modulation. The goal of this approach is to facilitate the delivery of compensated or intensity-modulated fields. The present work gives an overview of these developments. The hardware requirements on MLCs for this special application are specified. Most commercially available MLCs fulfill these requirement sufficiently, however, the MLC control software is generally not capable of controlling an MLC dynamically. There is also the question of how to verify the dynamic movement of the leaves. Some minimum requirements on a control software suitable for application in clinical practice are therefore specified. An alternative, the stepwise or 'quasi-dynamic' movement of the MLC-leaves, is also discussed with respect to practicality. In this case the control is easier, but the demands on the stability of the accelerator for small dose deliveries are higher. Nevertheless, it can be expected that, for reasons of ease of control and verification, the quasi-dynamic technique will become the method of choice in the near future, while the slightly more effective fully dynamic technique will become available later in the future. In any case, multileaf modulation is an interesting and important alternative to the tomotherapy-concept

Actin depolymerization enhances adipogenic differentiation in human stromal stem cells

DEFF Research Database (Denmark)

Chen, Li; Hu, Huimin; Qiu, Weimin

2018-01-01

Human stromal stem cells (hMSCs) differentiate into adipocytes that play a role in skeletal tissue homeostasis and whole body energy metabolism. During adipocyte differentiation, hMSCs exhibit significant changes in cell morphology suggesting changes in cytoskeletal organization. Here, we examined...... the effect of direct modulation of actin microfilament dynamics on adipocyte differentiation. Stabilizing actin filaments in hMSCs by siRNA-mediated knock down of the two main actin depolymerizing factors (ADFs): Cofilin 1 (CFL1) and Destrin (DSTN) or treating the cells by Phalloidin reduced adipocyte...

Dynamic and Progressive Control of DNA Origami Conformation by Modulating DNA Helicity with Chemical Adducts.

Science.gov (United States)

Chen, Haorong; Zhang, Hanyu; Pan, Jing; Cha, Tae-Gon; Li, Shiming; Andréasson, Joakim; Choi, Jong Hyun

2016-05-24

DNA origami has received enormous attention for its ability to program complex nanostructures with a few nanometer precision. Dynamic origami structures that change conformation in response to environmental cues or external signals hold great promises in sensing and actuation at the nanoscale. The reconfiguration mechanism of existing dynamic origami structures is mostly limited to single-stranded hinges and relies almost exclusively on DNA hybridization or strand displacement. Here, we show an alternative approach by demonstrating on-demand conformation changes with DNA-binding molecules, which intercalate between base pairs and unwind DNA double helices. The unwinding effect modulates the helicity mismatch in DNA origami, which significantly influences the internal stress and the global conformation of the origami structure. We demonstrate the switching of a polymerized origami nanoribbon between different twisting states and a well-constrained torsional deformation in a monomeric origami shaft. The structural transformation is shown to be reversible, and binding isotherms confirm the reconfiguration mechanism. This approach provides a rapid and reversible means to change DNA origami conformation, which can be used for dynamic and progressive control at the nanoscale.

Requirements for a Dynamic Solvent Extraction Module to Support Development of Advanced Technologies for the Recycle of Used Nuclear Fuel

Energy Technology Data Exchange (ETDEWEB)

Jack Law; Veronica Rutledge; Candido Pereira; Jackie Copple; Kurt Frey; John Krebs; Laura Maggos; Kevin Nichols; Kent Wardle; Pratap Sadasivan; Valmor DeAlmieda; David Depaoli

2011-06-01

The Department of Energy's Nuclear Energy Advanced Modeling and Simulation (NEAMS) Program has been established to create and deploy next generation, verified and validated nuclear energy modeling and simulation capabilities for the design, implementation, and operation of future nuclear energy systems to improve the U.S. energy security. As part of the NEAMS program, Integrated Performance and Safety Codes (IPSC's) are being produced to significantly advance the status of modeling and simulation of energy systems beyond what is currently available to the extent that the new codes be readily functional in the short term and extensible in the longer term. The four IPSC areas include Safeguards and Separations, Reactors, Fuels, and Waste Forms. As part of the Safeguards and Separations (SafeSeps) IPSC effort, interoperable process models are being developed that enable dynamic simulation of an advanced separations plant. A SafeSepss IPSC 'toolkit' is in development to enable the integration of separation process modules and safeguards tools into the design process by providing an environment to compose, verify and validate a simulation application to be used for analysis of various plant configurations and operating conditions. The modules of this toolkit will be implemented on a modern, expandable architecture with the flexibility to explore and evaluate a wide range of process options while preserving their stand-alone usability. Modules implemented at the plant-level will initially incorporate relatively simple representations for each process through a reduced modeling approach. Final versions will incorporate the capability to bridge to subscale models to provide required fidelity in chemical and physical processes. A dynamic solvent extraction model and its module implementation are needed to support the development of this integrated plant model. As a stand-alone application, it will also support solvent development of extraction flowsheets

Self oscillating PWM modulators, a topological comparison

DEFF Research Database (Denmark)

Poulsen, Søren; Andersen, Michael Andreas E.

2004-01-01

or fs/ð range respectively, where fs is the switching frequency of the converter. For some applications this will require unacceptable high switching frequency to achieve enough control loop bandwidth for the desired dynamic performance. With self oscillating modulators, the open loop bandwidth is equal...... to fs which makes this type of modulators an excellent choice for a wide range of applications. Self oscillating PWM modulators can be made in a number of ways, either as voltage or current mode modulators, and the self oscillating behavior can be achieved either by using hysteresis control...... or by shaping the open loop function of the modulator so its gain and phase response causes a closed loop natural oscillation. The two main types of self oscillating modulators have many similarities, but differences in dynamic performance and linearity are present. The work presented is related to the author...

Magnolol inhibits migration of vascular smooth muscle cells via cytoskeletal remodeling pathway to attenuate neointima formation

International Nuclear Information System (INIS)

Karki, Rajendra; Kim, Seong-Bin; Kim, Dong-Wook

2013-01-01

Background: Increased proliferation and migration of vascular smooth muscle cells (VSMCs) contribute importantly to the formation of both atherosclerotic and restenotic lesions. The objective of this study was to investigate the effect of magnolol on VSMC migration. Methods: The proteolytic activity of matrix metalloproteinases (MMPs) in tumor necrosis factor alpha (TNF-α) stimulated VSMCs was performed by gelatin zymography. VSMC migration was assessed by wound healing and Boyden chamber methods. Collagen induced VSMC adhesion was determined by spectrofluorimeter and stress fibers formation was evaluated by fluorescence microscope. The expression of signaling molecules involved in stress fibers formation was determined by western blot. The phosphorylation of myosin light chain (MLC20) was determined by urea-glycerol polyacrylamide gel electrophoresis. Immunohistochemistry was performed to determine the expression of β1-integrin and collagen type I in the injured carotid arteries of rats on day 35 after vascular injury. Results: VSMC migration was strongly inhibited by magnolol without affecting MMPs expression. Also, magnolol inhibited β1-integrin expression, FAK phosphorylation and RhoA and Cdc42 activation to inhibit the collagen induced stress fibers formation. Moreover, magnolol inhibited the phosphorylation of MLC20. Our in vivo results showed that magnolol inhibited β1-integrin expression, collagen type I deposition and FAK phosphorylation in injured carotid arteries without affecting MMP-2 activity. Conclusions: Magnolol inhibited VSMC migration via inhibition of cytoskeletal remodeling pathway to attenuate neointima formation. General significance: This study provides a rationale for further evaluation of magnolol for the management of atherosclerosis and restenosis. - Highlights: • Magnolol strongly inhibited migration of VSMCs. • Magnolol inhibited stress fibers formation. • MLC20 phosphorylation was also inhibited by magnolol. • Anti

Magnolol inhibits migration of vascular smooth muscle cells via cytoskeletal remodeling pathway to attenuate neointima formation

Energy Technology Data Exchange (ETDEWEB)

Karki, Rajendra [Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City (United States); Department of Oriental Medicine Resources, Mokpo National University (Korea, Republic of); Kim, Seong-Bin [Jeollanamdo Development Institute for Korean Traditional Medicine, Jangheung gun, Jeollanamdo (Korea, Republic of); Kim, Dong-Wook, E-mail: dbkim@mokpo.ac.kr [Department of Oriental Medicine Resources, Mokpo National University (Korea, Republic of)

2013-12-10

Background: Increased proliferation and migration of vascular smooth muscle cells (VSMCs) contribute importantly to the formation of both atherosclerotic and restenotic lesions. The objective of this study was to investigate the effect of magnolol on VSMC migration. Methods: The proteolytic activity of matrix metalloproteinases (MMPs) in tumor necrosis factor alpha (TNF-α) stimulated VSMCs was performed by gelatin zymography. VSMC migration was assessed by wound healing and Boyden chamber methods. Collagen induced VSMC adhesion was determined by spectrofluorimeter and stress fibers formation was evaluated by fluorescence microscope. The expression of signaling molecules involved in stress fibers formation was determined by western blot. The phosphorylation of myosin light chain (MLC20) was determined by urea-glycerol polyacrylamide gel electrophoresis. Immunohistochemistry was performed to determine the expression of β1-integrin and collagen type I in the injured carotid arteries of rats on day 35 after vascular injury. Results: VSMC migration was strongly inhibited by magnolol without affecting MMPs expression. Also, magnolol inhibited β1-integrin expression, FAK phosphorylation and RhoA and Cdc42 activation to inhibit the collagen induced stress fibers formation. Moreover, magnolol inhibited the phosphorylation of MLC20. Our in vivo results showed that magnolol inhibited β1-integrin expression, collagen type I deposition and FAK phosphorylation in injured carotid arteries without affecting MMP-2 activity. Conclusions: Magnolol inhibited VSMC migration via inhibition of cytoskeletal remodeling pathway to attenuate neointima formation. General significance: This study provides a rationale for further evaluation of magnolol for the management of atherosclerosis and restenosis. - Highlights: • Magnolol strongly inhibited migration of VSMCs. • Magnolol inhibited stress fibers formation. • MLC20 phosphorylation was also inhibited by magnolol. • Anti

Dynamic Imbalance Would Counter Offcenter Thrust

Science.gov (United States)

Mccanna, Jason

1994-01-01

Dynamic imbalance generated by offcenter thrust on rotating body eliminated by shifting some of mass of body to generate opposing dynamic imbalance. Technique proposed originally for spacecraft including massive crew module connected via long, lightweight intermediate structure to massive engine module, such that artificial gravitation in crew module generated by rotating spacecraft around axis parallel to thrust generated by engine. Also applicable to dynamic balancing of rotating terrestrial equipment to which offcenter forces applied.

Dynamic intensity-modulated non-coplanar arc radiotherapy (INCA) for head and neck cancer

International Nuclear Information System (INIS)

Krayenbuehl, Jerome; Davis, J. Bernard; Ciernik, I. Frank

2006-01-01

Background and purpose: To define the potential advantages of intensity-modulated radiotherapy (IMRT) applied using a non-coplanar dynamic arc technique for the treatment of head and neck cancer. Materials and methods: External beam radiotherapy (EBRT) was planned in ten patients with head and neck cancer using coplanar IMRT and non-coplanar arc techniques, termed intensity modulated non-coplanar arc EBRT (INCA). Planning target volumes (PTV1) of first order covered the gross tumor volume and surrounding clinical target volume treated with 68-70 Gy, whereas PTV2 covered the elective lymph nodes with 54-55 Gy using a simultaneous internal boost. Treatment plan comparison between IMRT and INCA was carried out using dose-volume histogram and 'equivalent uniform dose' (EUD). Results: INCA resulted in better dose coverage and homogeneity of the PTV1, PTV2, and reduced dose delivered to most of the organs at risk (OAR). For the parotid glands, a reduction of the mean dose of 2.9 (±2.0) Gy was observed (p 0.002), the mean dose to the larynx was reduced by 6.9 (±2.9) Gy (p 0.003), the oral mucosa by 2.4 (±1.1) Gy (p < 0.001), and the maximal dose to the spinal cord by 3.2 (±1.7) Gy (p = 0.004). The mean dose to the brain was increased by 3.0 (±1.4) Gy (p = 0.002) and the mean lung dose increased by 0.2 (±0.4) Gy (p = 0.87). The EUD suggested better avoidance of the OAR, except for the lung, and better coverage and dose uniformity were achieved with INCA compared to IMRT. Conclusion: Dose delivery accuracy with IMRT using a non-coplanar dynamic arc beam geometry potentially improves treatment of head and neck cancer

Analysis of plasma dynamic response to modulated electron cyclotron heating in TCV tokamak

International Nuclear Information System (INIS)

Pavlov, I.

2008-01-01

different types of modulating signals. This set-up was used to study simultaneous propagation of heat waves induced by MECH in non-sawtoothing plasmas, and in discharges with sawtooth activity. A new analysis method for the characterization of the plasma non-linear dynamic response to modulated heating was developed on the basis of Higher Order Spectral Analysis (HOSA) technique. This method applied to signals from different diagnostics, such as electron cyclotron emission and soft X-ray measurements, was extensively used to quantitatively characterize the effect of nonlinear phase coupling. In sawtooth free discharges a detailed analysis of the propagation of heat waves demonstrated that their phase coupling is solely related to properties of heat sources. It was demonstrated that if two heat waves are induced by non-coupled power sources (multi-beam MECH) then no phase coupling occurs. In the opposite case, when a source of perturbation (MECH) contains coupled harmonics, the corresponding heat waves demonstrate phase coupling. It was shown that these coupled heat waves loose their phase coherence while propagating in plasma. The dissipation of phase coupling is due to different phase velocities of heat waves and their diffusive damping. The new type of ECH power modulation accompanied with bicoherence analysis was proposed as a candidate for a reliable identification of EC power deposition location in a case of high frequency and low modulation depth MECH, including multi-beam heating. This type of MECH can be particularly important for real time control applications. In cases when MECH is applied to sawtoothing plasmas a direct experimental evidence of MECH-sawtooth non-linear phase coupling has been demonstrated using HOSA techniques, in particular bispectrum and bicoherence profiles. The detailed analysis presented here demonstrates a direct proof of periodic modification of sawtooth behavior by modulated ECH. It was shown that a simple diffusive model for the

Synthetic polymeric substrates as potent pro-oxidant versus anti-oxidant regulators of cytoskeletal remodeling and cell apoptosis.

Science.gov (United States)

Sung, Hak-Joon; Chandra, Prafulla; Treiser, Matthew D; Liu, Er; Iovine, Carmine P; Moghe, Prabhas V; Kohn, Joachim

2009-03-01

The role of reactive oxygen species (ROS)-mediated cell signal transduction pathways emanating from engineered cell substrates remains unclear. To elucidate the role, polymers derived from the amino acid L-tyrosine were used as synthetic matrix substrates. Variations in their chemical properties were created by co-polymerizing hydrophobic L-tyrosine derivatives with uncharged hydrophilic poly(ethylene glycol) (PEG, Mw = 1,000 Da), and negatively charged desaminotyrosyl-tyrosine (DT). These substrates were characterized for their intrinsic ability to generate ROS, as well as their ability to elicit Saos-2 cell responses in terms of intracellular ROS production, actin remodeling, and apoptosis. PEG-containing substrates induced both exogenous and intracellular ROS production, whereas the charged substrates reduced production of both types, indicating a coupling of exogenous ROS generation and intracellular ROS production. Furthermore, PEG-mediated ROS induction caused nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase and an increase in caspase-3 activity, confirming a link with apoptosis. PEG-rich pro-oxidant substrates caused cytoskeletal actin remodeling through beta-actin cleavage by caspase-3 into fractins. The fractins co-localized to the mitochondria and reduced the mitochondrial membrane potential. The remnant cytosolic beta-actin was polymerized and condensed, events consistent with apoptotic cell shrinkage. The cytoskeletal remodeling was integral to the further augmentation of intracellular ROS production. Conversely, the anti-oxidant DT-containing charged substrates suppressed the entire cascade of apoptotic progression. We demonstrate that ROS activity serves an important role in "outside-in" signaling for cells grown on substrates: the ROS activity couples exogenous stress, driven by substrate composition, to changes in intracellular signaling. This signaling causes cell apoptosis, which is mediated by actin remodeling.

Spatiotemporal brain dynamics of emotional face processing modulations induced by the serotonin 1A/2A receptor agonist psilocybin.

Science.gov (United States)

Bernasconi, Fosco; Schmidt, André; Pokorny, Thomas; Kometer, Michael; Seifritz, Erich; Vollenweider, Franz X

2014-12-01

Emotional face processing is critically modulated by the serotonergic system. For instance, emotional face processing is impaired by acute psilocybin administration, a serotonin (5-HT) 1A and 2A receptor agonist. However, the spatiotemporal brain mechanisms underlying these modulations are poorly understood. Here, we investigated the spatiotemporal brain dynamics underlying psilocybin-induced modulations during emotional face processing. Electrical neuroimaging analyses were applied to visual evoked potentials in response to emotional faces, following psilocybin and placebo administration. Our results indicate a first time period of strength (i.e., Global Field Power) modulation over the 168-189 ms poststimulus interval, induced by psilocybin. A second time period of strength modulation was identified over the 211-242 ms poststimulus interval. Source estimations over these 2 time periods further revealed decreased activity in response to both neutral and fearful faces within limbic areas, including amygdala and parahippocampal gyrus, and the right temporal cortex over the 168-189 ms interval, and reduced activity in response to happy faces within limbic and right temporo-occipital brain areas over the 211-242 ms interval. Our results indicate a selective and temporally dissociable effect of psilocybin on the neuronal correlates of emotional face processing, consistent with a modulation of the top-down control. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Quantitative Evaluation of Stomatal Cytoskeletal Patterns during the Activation of Immune Signaling in Arabidopsis thaliana.

Directory of Open Access Journals (Sweden)

Masaki Shimono

Full Text Available Historically viewed as primarily functioning in the regulation of gas and water vapor exchange, it is now evident that stomata serve an important role in plant immunity. Indeed, in addition to classically defined functions related to cell architecture and movement, the actin cytoskeleton has emerged as a central component of the plant immune system, underpinning not only processes related to cell shape and movement, but also receptor activation and signaling. Using high resolution quantitative imaging techniques, the temporal and spatial changes in the actin microfilament array during diurnal cycling of stomatal guard cells has revealed a highly orchestrated transition from random arrays to ordered bundled filaments. While recent studies have demonstrated that plant stomata close in response to pathogen infection, an evaluation of stimulus-induced changes in actin cytoskeletal dynamics during immune activation in the guard cell, as well as the relationship of these changes to the function of the actin cytoskeleton and stomatal aperture, remains undefined. In the current study, we employed quantitative cell imaging and hierarchical clustering analyses to define the response of the guard cell actin cytoskeleton to pathogen infection and the elicitation of immune signaling. Using this approach, we demonstrate that stomatal-localized actin filaments respond rapidly, and specifically, to both bacterial phytopathogens and purified pathogen elicitors. Notably, we demonstrate that higher order temporal and spatial changes in the filament array show distinct patterns of organization during immune activation, and that changes in the naïve diurnal oscillations of guard cell actin filaments are perturbed by pathogens, and that these changes parallel pathogen-induced stomatal gating. The data presented herein demonstrate the application of a highly tractable and quantifiable method to assign transitions in actin filament organization to the activation of

Transient Response Dynamic Module Modifications to Include Static and Kinetic Friction Effects

Science.gov (United States)

Misel, J. E.; Nenno, S. B.; Takahashi, D.

1984-01-01

A methodology that supports forced transient response dynamic solutions when both static and kinetic friction effects are included in a structural system model is described. Modifications that support this type of nonlinear transient response solution are summarized for the transient response dynamics (TRD) NASTRAN module. An overview of specific modifications for the NASTRAN processing subroutines, INITL, TRD1C, and TRD1D, are described with further details regarding inspection of nonlinear input definitions to define the type of nonlinear solution required, along with additional initialization requirements and specific calculation subroutines to successfully solve the transient response problem. The extension of the basic NASTRAN nonlinear methodology is presented through several stages of development to the point where constraint equations and residual flexibility effects are introduced into the finite difference Newmark-Beta recurrsion formulas. Particular emphasis is placed on cost effective solutions for large finite element models such as the Space Shuttle with friction degrees of freedom between the orbiter and payloads mounted in the cargo bay. An alteration to the dynamic finite difference equations of motion is discussed, which allows one to include friction effects at reasonable cost for large structural systems such as the Space Shuttle. Data are presented to indicate the possible impact of transient friction loads to the payload designer for the Space Shuttle. Transient response solution data are also included, which compare solutions without friction forces and those with friction forces for payloads mounted in the Space Shuttle cargo bay. These data indicate that payload components can be sensitive to friction induced loads.

Lysophosphatidic acid receptor activation affects the C13NJ microglia cell line proteome leading to alterations in glycolysis, motility, and cytoskeletal architecture

Science.gov (United States)

Bernhart, Eva; Kollroser, Manfred; Rechberger, Gerald; Reicher, Helga; Heinemann, Akos; Schratl, Petra; Hallström, Seth; Wintersperger, Andrea; Nusshold, Christoph; DeVaney, Trevor; Zorn-Pauly, Klaus; Malli, Roland; Graier, Wolfgang; Malle, Ernst; Sattler, Wolfgang

2014-01-01

Microglia, the immunocompetent cells of the CNS, are rapidly activated in response to injury and microglia migration towards and homing at damaged tissue plays a key role in CNS regeneration. Lysophosphatidic acid (LPA) is involved in signaling events evoking microglia responses through cognate G protein-coupled receptors. Here we show that human immortalized C13NJ microglia express LPA receptor subtypes LPA1, LPA2, and LPA3 on mRNA and protein level. LPA activation of C13NJ cells induced Rho and extracellular signal-regulated kinase activation and enhanced cellular ATP production. In addition, LPA induced process retraction, cell spreading, led to pronounced changes of the actin cytoskeleton and reduced cell motility, which could be reversed by inhibition of Rho activity. To get an indication about LPA-induced global alterations in protein expression patterns a 2-D DIGE/LC-ESI-MS proteomic approach was applied. On the proteome level the most prominent changes in response to LPA were observed for glycolytic enzymes and proteins regulating cell motility and/or cytoskeletal dynamics. The present findings suggest that naturally occurring LPA is a potent regulator of microglia biology. This might be of particular relevance in the pathophysiological context of neurodegenerative disorders where LPA concentrations can be significantly elevated in the CNS. PMID:19899077

One isoform of Arg/Abl2 tyrosine kinase is nuclear and the other seven cytosolic isoforms differently modulate cell morphology, motility and the cytoskeleton

International Nuclear Information System (INIS)

Bianchi, Cristina; Torsello, Barbara; Di Stefano, Vitalba; Zipeto, Maria A.; Facchetti, Rita; Bombelli, Silvia; Perego, Roberto A.

2013-01-01

The non-receptor tyrosine kinase Abelson related gene (Arg/Abl2) regulates cell migration and morphogenesis by modulating the cytoskeleton. Arg promotes actin-based cell protrusions and spreading, and inhibits cell migration by attenuating stress fiber formation and contractility via activation of the RhoA inhibitor, p190RhoGAP, and by regulating focal adhesion dynamics also via CrkII phosphorylation. Eight full-length Arg isoforms with different N- and C-termini are endogenously expressed in human cells. In this paper, the eight Arg isoforms, subcloned in the pFLAG-CMV2 vector, were transfected in COS-7 cells in order to study their subcellular distribution and role in cell morphology, migration and cytoskeletal modulation. The transfected 1BSCTS Arg isoform has a nuclear distribution and phosphorylates CrkII in the nucleus, whilst the other isoforms are detected in the cytoplasm. The 1BLCTL, 1BSCTL, 1ASCTS isoforms were able to significantly decrease stress fibers, induce cell shrinkage and filopodia-like protrusions with a significant increase in p190RhoGAP phosphorylation. In contrast, 1ALCTL, 1ALCTS, 1ASCTL and 1BLCTS isoforms do not significantly decrease stress fibers and induce the formation of retraction tail-like protrusions. The 1BLCTL and 1ALCTL isoforms have different effects on cell migration and focal adhesions. All these data may open new perspectives to study the mechanisms of cell invasiveness. -Highlights: • Each of the eight Arg isoforms was transfected in COS-7 cells. • Only the 1BSCTS Arg isoform has a nuclear distribution in transfected cells. • The cytoplasmic isoforms and F-actin colocalize cortically and in cell protrusions. • Arg isoforms differently phosphorylate p190RhoGAP and CrkII. • Arg isoforms differently modulate stress fibers, cell protrusions and motility

One isoform of Arg/Abl2 tyrosine kinase is nuclear and the other seven cytosolic isoforms differently modulate cell morphology, motility and the cytoskeleton

Energy Technology Data Exchange (ETDEWEB)

Bianchi, Cristina; Torsello, Barbara; Di Stefano, Vitalba; Zipeto, Maria A.; Facchetti, Rita; Bombelli, Silvia; Perego, Roberto A., E-mail: roberto.perego@unimib.it

2013-08-01

The non-receptor tyrosine kinase Abelson related gene (Arg/Abl2) regulates cell migration and morphogenesis by modulating the cytoskeleton. Arg promotes actin-based cell protrusions and spreading, and inhibits cell migration by attenuating stress fiber formation and contractility via activation of the RhoA inhibitor, p190RhoGAP, and by regulating focal adhesion dynamics also via CrkII phosphorylation. Eight full-length Arg isoforms with different N- and C-termini are endogenously expressed in human cells. In this paper, the eight Arg isoforms, subcloned in the pFLAG-CMV2 vector, were transfected in COS-7 cells in order to study their subcellular distribution and role in cell morphology, migration and cytoskeletal modulation. The transfected 1BSCTS Arg isoform has a nuclear distribution and phosphorylates CrkII in the nucleus, whilst the other isoforms are detected in the cytoplasm. The 1BLCTL, 1BSCTL, 1ASCTS isoforms were able to significantly decrease stress fibers, induce cell shrinkage and filopodia-like protrusions with a significant increase in p190RhoGAP phosphorylation. In contrast, 1ALCTL, 1ALCTS, 1ASCTL and 1BLCTS isoforms do not significantly decrease stress fibers and induce the formation of retraction tail-like protrusions. The 1BLCTL and 1ALCTL isoforms have different effects on cell migration and focal adhesions. All these data may open new perspectives to study the mechanisms of cell invasiveness. -Highlights: • Each of the eight Arg isoforms was transfected in COS-7 cells. • Only the 1BSCTS Arg isoform has a nuclear distribution in transfected cells. • The cytoplasmic isoforms and F-actin colocalize cortically and in cell protrusions. • Arg isoforms differently phosphorylate p190RhoGAP and CrkII. • Arg isoforms differently modulate stress fibers, cell protrusions and motility.

Microsoft Dynamics GP 2013 implementation

CERN Document Server

Yudin, Victoria

2013-01-01

A step-by-step guide for planning and carrying out your Microsoft Dynamics GP 2013 implementation. Detailed descriptions and illustrations of setup screens and practical examples and advice are included for the Dynamics GP system and core modules.If you are a new or existing Microsoft Dynamics GP consultant or an end user who wants to implement, install, and set up core modules of Dynamics GP 2013, then this book is for you. A basic understanding of business management systems and either Dynamics GP or a similar application is recommended.

Mechanisms of mechanical strain memory in airway smooth muscle.

Science.gov (United States)

Kim, Hak Rim; Hai, Chi-Ming

2005-10-01

We evaluated the hypothesis that mechanical deformation of airway smooth muscle induces structural remodeling of airway smooth muscle cells, thereby modulating mechanical performance in subsequent contractions. This hypothesis implied that past experience of mechanical deformation was retained (or "memorized") as structural changes in airway smooth muscle cells, which modulated the cell's subsequent contractile responses. We termed this phenomenon mechanical strain memory. Preshortening has been found to induce attenuation of both force and isotonic shortening velocity in cholinergic receptor-activated airway smooth muscle. Rapid stretching of cholinergic receptor-activated airway smooth muscle from an initial length to a final length resulted in post-stretch force and myosin light chain phosphorylation that correlated significantly with initial length. Thus post-stretch muscle strips appeared to retain memory of the initial length prior to rapid stretch (mechanical strain memory). Cytoskeletal recruitment of actin- and integrin-binding proteins and Erk 1/2 MAPK appeared to be important mechanisms of mechanical strain memory. Sinusoidal length oscillation led to force attenuation during oscillation and in subsequent contractions in intact airway smooth muscle, and p38 MAPK appeared to be an important mechanism. In contrast, application of local mechanical strain to cultured airway smooth muscle cells induced local actin polymerization and cytoskeletal stiffening. It is conceivable that deep inspiration-induced bronchoprotection may be a manifestation of mechanical strain memory such that mechanical deformation from past breathing cycles modulated the mechanical performance of airway smooth muscle in subsequent cycles in a continuous and dynamic manner.

In vivo antibody-mediated modulation of aminopeptidase A in mouse proximal tubular epithelial cells.

Science.gov (United States)

Mentzel, S; Dijkman, H B; van Son, J P; Wetzels, J F; Assmann, K J

1999-07-01

Aminopeptidase A (APA) is one of the many renal hydrolases. In mouse kidney, APA is predominantly expressed on the brush borders and sparsely on the basolateral membranes of proximal tubular epithelial cells. However, when large amounts of monoclonal antibodies (MAbs) against APA were injected into mice, we observed strong binding of the MAbs to the basolateral membranes, whereas the MAbs bound only transiently to the brush borders of the proximal tubular epithelial cells. In parallel, APA itself disappeared from the brush borders by both endocytosis and shedding, whereas it was increasingly expressed on the basolateral sides. Using ultrastructural immunohistology, we found no evidence for transcellular transport of endocytosed APA to the basolateral side of the proximal tubular epithelial cells. The absence of transcellular transport was confirmed by experiments in which we used a low dose of the MAbs. Such a low dose did not result in binding of the MAbs to the brush borders and had no effect on the presence of APA in the brush borders of the proximal tubular epithelial cells. In these experiments we still could observe binding of the MAbs to the basolateral membranes in parallel with the local appearance of APA. In addition, treatment of mice with chlorpromazine, a calmodulin antagonist that interferes with cytoskeletal function, largely inhibited the MAb-induced modulation of APA. Our studies suggest that injection of MAbs to APA specifically interrupts the normal intracellular traffic of this enzyme in proximal tubular epithelial cells. This intracellular transport is dependent on the action of cytoskeletal proteins.

Thermal Equilibrium Dynamic Control Based on DPWM Dual-Mode Modulation of High Power NPC Three-Level Inverter

OpenAIRE

Xu, Shi-Zhou; He, Feng-You

2016-01-01

In some special applications of NPC three-level inverters, such as mine hoist, there exist special conditions of overloading during the whole hoisting process and large overload in starting stage, during which the power-loss calculation of power devices and thermal control are important factors affecting the thermal stability of inverters. The principles of SVPWM and DPWM were described in this paper firstly, based on which the dynamic power losses of the two modulations of hoist in single pe...

Effect of collagen I and fibronectin on the adhesion, elasticity and cytoskeletal organization of prostate cancer cells.

Science.gov (United States)

Docheva, Denitsa; Padula, Daniela; Schieker, Matthias; Clausen-Schaumann, Hauke

2010-11-12

Despite of intensive research efforts, the precise mechanism of prostate cancer metastasis in bone is still not fully understood. Several studies have suggested that specific matrix production by the bone cells, such as collagen I, supports cancer cell invasion. The aim of this study was to investigate the effect of collagen I (COL1) and fibronectin (FN) on cell adhesion, cell elasticity and cytoskeletal organization of prostate cancer cells. Two cell lines, bone marrow- (PC3) and lymph node-derived (LNCaP) were cultivated on COL1 and FN (control protein). By using a quantitative adhesion assay and time-lapse analysis, it was found that PC3, but not LNCaP, adhered strongly and were more spread on COL1. Next, PC3 and LNCaP were evaluated by atomic force microscopy (AFM) and flatness shape factor and cellular Young's modulus were calculated. The shape analysis revealed that PC3 were significantly flatter when grown on COL1 in comparison to LNCaP. In general, PC3 were also significantly stiffer than LNCaP and furthermore, their stiffness increased upon interaction with COL1. Since cell stiffness is strongly dependent on actin organization, phalloidin-based actin staining was performed and revealed that, of the two cell types as well as the two different matrix proteins, only PC3 grown on COL1 formed robust actin cytoskeleton. In conclusion, our study showed that PC3 cells have a strong affinity towards COL1. On this matrix protein, the cells adhered strongly and underwent a specific cell flattening. Moreover, with the establishment of PC3 contact to COL1 a significant increase of PC3 stiffness was observed due to a profound cytoskeletal rearrangement. Copyright © 2010 Elsevier Inc. All rights reserved.

Developing the impact testing module with labVIEW

International Nuclear Information System (INIS)

Choi, Ki Soo; Jeon, Soo Hong; Jeong, Weui Bong

2007-01-01

Fast Fourier Transformation (FFT) is one of the most useful way to analyze response signal for the purpose of grasping the dynamic characteristics of system. Vibration test using impact hammer is typical and simple experimental method widely used for catching hold of dynamic peculiar characters and modal behaviors of system. In this thesis, impact testing module for NI-PXI equipment is developed. The analyzing and visualizing module are developed with labVIEW tool. A user can see quickly and easily modal shape of system after analyzing acquired data. This developed module will be expected to build up more convenient and serviceable measurement system

Dynamic link: user's manual

International Nuclear Information System (INIS)

Harada, Hiroo; Asai, Kiyoshi; Kihara, Kazuhisa.

1981-09-01

The purpose of dynamic link facility is to link a load module dynamically only when it is used in execution time. The facility is very useful for development, execution and maintenance of a large scale computer program which is too big to be saved as one load module in main memory, or it is poor economy to save it due to many unused subroutines depending on an input. It is also useful for standardization and common utilization of programs. Standard usage of dynamic link facility of FACOM M-200 computer system, a software tool which analyzes the effect of dynamic link facility and application of dynamic link to nuclear codes are described. (author)

Phosphomimetic mutation of cysteine string protein-α increases the rate of regulated exocytosis by modulating fusion pore dynamics in PC12 cells.

Directory of Open Access Journals (Sweden)

Ning Chiang

Full Text Available BACKGROUND: Cysteine string protein-α (CSPα is a chaperone to ensure protein folding. Loss of CSPα function associates with many neurological diseases. However, its function in modulating regulated exocytosis remains elusive. Although cspα-knockouts exhibit impaired synaptic transmission, overexpression of CSPα in neuroendocrine cells inhibits secretion. These seemingly conflicting results lead to a hypothesis that CSPα may undergo a modification that switches its function in regulating neurotransmitter and hormone secretion. Previous studies implied that CSPα undergoes phosphorylation at Ser10 that may influence exocytosis by altering fusion pore dynamics. However, direct evidence is missing up to date. METHODOLOGY/PRINCIPAL FINDINGS: Using amperometry, we investigated how phosphorylation at Ser10 of CSPα (CSPα-Ser10 modulates regulated exocytosis and if this modulation involves regulating a specific kinetic step of fusion pore dynamics. The real-time exocytosis of single vesicles was detected in PC12 cells overexpressing control vector, wild-type CSPα (WT, the CSPα phosphodeficient mutant (S10A, or the CSPα phosphomimetic mutants (S10D and S10E. The shapes of amperometric signals were used to distinguish the full-fusion events (i.e., prespike feet followed by spikes and the kiss-and-run events (i.e., square-shaped flickers. We found that the secretion rate was significantly increased in cells overexpressing S10D or S10E compared to WT or S10A. Further analysis showed that overexpression of S10D or S10E prolonged fusion pore lifetime compared to WT or S10A. The fraction of kiss-and-run events was significantly lower but the frequency of full-fusion events was higher in cells overexpressing S10D or S10E compared to WT or S10A. Advanced kinetic analysis suggests that overexpression of S10D or S10E may stabilize open fusion pores mainly by inhibiting them from closing. CONCLUSIONS/SIGNIFICANCE: CSPα may modulate fusion pore dynamics

MAL Overexpression Leads to Disturbed Expression of Genes That Influence Cytoskeletal Organization and Differentiation of Schwann Cells

Directory of Open Access Journals (Sweden)

Daniela Schmid

2014-09-01

Full Text Available In the developing peripheral nervous system, a coordinated reciprocal signaling between Schwann cells and axons is crucial for accurate myelination. The myelin and lymphocyte protein MAL is a component of lipid rafts that is important for targeting proteins and lipids to distinct domains. MAL overexpression impedes peripheral myelinogenesis, which is evident by a delayed onset of myelination and reduced expression of the myelin protein zero (Mpz/P0 and the low-affinity neurotrophin receptor p75NTR . This study shows that MAL overexpression leads to a significant reduction of Mpz and p75NTR expression in primary mouse Schwann cell cultures, which was already evident before differentiation, implicating an effect of MAL in early Schwann cell development. Their transcription was robustly reduced, despite normal expression of essential transcription factors and receptors. Further, the cAMP response element-binding protein (CREB and phosphoinositide 3-kinase signaling pathways important for Schwann cell differentiation were correctly induced, highlighting that other so far unknown rate limiting factors do exist. We identified novel genes expressed by Schwann cells in a MAL-dependent manner in vivo and in vitro. A number of those, including S100a4, RhoU and Krt23, are implicated in cytoskeletal organization and plasma membrane dynamics. We showed that S100a4 is predominantly expressed by nonmyelinating Schwann cells, whereas RhoU was localized within myelin membranes, and Krt23 was detected in nonmyelinating as well as in myelinating Schwann cells. Their differential expression during early peripheral nerve development further underlines their possible role in influencing Schwann cell differentiation and myelination.

RIT1 controls actin dynamics via complex formation with RAC1/CDC42 and PAK1.

Directory of Open Access Journals (Sweden)

Uta Meyer Zum Büschenfelde

2018-05-01

Full Text Available RIT1 belongs to the RAS family of small GTPases. Germline and somatic RIT1 mutations have been identified in Noonan syndrome (NS and cancer, respectively. By using heterologous expression systems and purified recombinant proteins, we identified the p21-activated kinase 1 (PAK1 as novel direct effector of RIT1. We found RIT1 also to directly interact with the RHO GTPases CDC42 and RAC1, both of which are crucial regulators of actin dynamics upstream of PAK1. These interactions are independent of the guanine nucleotide bound to RIT1. Disease-causing RIT1 mutations enhance protein-protein interaction between RIT1 and PAK1, CDC42 or RAC1 and uncouple complex formation from serum and growth factors. We show that the RIT1-PAK1 complex regulates cytoskeletal rearrangements as expression of wild-type RIT1 and its mutant forms resulted in dissolution of stress fibers and reduction of mature paxillin-containing focal adhesions in COS7 cells. This effect was prevented by co-expression of RIT1 with dominant-negative CDC42 or RAC1 and kinase-dead PAK1. By using a transwell migration assay, we show that RIT1 wildtype and the disease-associated variants enhance cell motility. Our work demonstrates a new function for RIT1 in controlling actin dynamics via acting in a signaling module containing PAK1 and RAC1/CDC42, and highlights defects in cell adhesion and migration as possible disease mechanism underlying NS.

RIT1 controls actin dynamics via complex formation with RAC1/CDC42 and PAK1.

Science.gov (United States)

Meyer Zum Büschenfelde, Uta; Brandenstein, Laura Isabel; von Elsner, Leonie; Flato, Kristina; Holling, Tess; Zenker, Martin; Rosenberger, Georg; Kutsche, Kerstin

2018-05-01

RIT1 belongs to the RAS family of small GTPases. Germline and somatic RIT1 mutations have been identified in Noonan syndrome (NS) and cancer, respectively. By using heterologous expression systems and purified recombinant proteins, we identified the p21-activated kinase 1 (PAK1) as novel direct effector of RIT1. We found RIT1 also to directly interact with the RHO GTPases CDC42 and RAC1, both of which are crucial regulators of actin dynamics upstream of PAK1. These interactions are independent of the guanine nucleotide bound to RIT1. Disease-causing RIT1 mutations enhance protein-protein interaction between RIT1 and PAK1, CDC42 or RAC1 and uncouple complex formation from serum and growth factors. We show that the RIT1-PAK1 complex regulates cytoskeletal rearrangements as expression of wild-type RIT1 and its mutant forms resulted in dissolution of stress fibers and reduction of mature paxillin-containing focal adhesions in COS7 cells. This effect was prevented by co-expression of RIT1 with dominant-negative CDC42 or RAC1 and kinase-dead PAK1. By using a transwell migration assay, we show that RIT1 wildtype and the disease-associated variants enhance cell motility. Our work demonstrates a new function for RIT1 in controlling actin dynamics via acting in a signaling module containing PAK1 and RAC1/CDC42, and highlights defects in cell adhesion and migration as possible disease mechanism underlying NS.

The cytoskeletal inhibitors latrunculin A and blebbistatin exert antitumorigenic properties in human hepatocellular carcinoma cells by interfering with intracellular HuR trafficking

International Nuclear Information System (INIS)

Doller, Anke; Badawi, Amel; Schmid, Tobias; Brauß, Thilo; Pleli, Thomas; Meyer zu Heringdorf, Dagmar; Piiper, Albrecht; Pfeilschifter, Josef; Eberhardt, Wolfgang

2015-01-01

The impact of the RNA-binding protein HuR for the post-transcriptional deregulation of tumor-relevant genes is well established. Despite of elevations in HuR expression levels, an increase in cytoplasmic HuR abundance in many cases correlates with a high grade of malignancy. Here, we demonstrated that administration of the actin-depolymerizing macrolide latrunculin A, or blebbistatin, an inhibitor of myosin II ATPase activity, caused a dose- and time-dependent reduction in the high cytoplasmic HuR content of HepG2 and Huh7 hepatocellular carcinoma (HCC) cells. Subcellular fractionation revealed that in addition, both inhibitors strongly attenuated cytoskeletal and membrane-bound HuR abundance and conversely increased the HuR amount in nuclear cell fractions. Concomitant with changes in intracellular HuR localization, both cytoskeletal inhibitors markedly decreased the half-lives of cyclooxygenase-2 (COX-2), cyclin A and cyclin D 1 encoding mRNAs resulting in a significant reduction in their expression levels in HepG2 cells. Importantly, a similar reduction in the expression of these HuR targets was achieved by a RNA interference (RNAi)-mediated knockdown of either HuR or nonmuscle myoin IIA. Using polysomal fractionation, we further demonstrate that the decrease in cytoplasmic HuR by latrunculin A or blebbistatin is accompanied by a marked change in the allocation of HuR and its mRNA cargo from polysomes to ribonucleoprotein (RNP) particles. Functionally, the basal migration and prostaglandin E 2 synthesis are similarly impaired in inhibitor-treated and stable HuR-knockdown HepG2 cells. Our data demonstrate that interfering with the actomyosin-dependent HuR trafficking may comprise a valid therapeutic option for antagonizing pathologic posttranscriptional gene expression by HuR and furthermore emphasize the potential benefit of HuR inhibitory strategies for treatment of HCC. - Highlights: • We tested the effects of latrunculin A and blebbistatin on different Hu

Micropatterned Azopolymer Surfaces Modulate Cell Mechanics and Cytoskeleton Structure.

Science.gov (United States)

Rianna, Carmela; Ventre, Maurizio; Cavalli, Silvia; Radmacher, Manfred; Netti, Paolo A

2015-09-30

Physical and chemical characteristics of materials are important regulators of cell behavior. In particular, cell elasticity is a fundamental parameter that reflects the state of a cell. Surface topography finely modulates cell fate and function via adhesion mediated signaling and cytoskeleton generated forces. However, how topographies alter cell mechanics is still unclear. In this work we have analyzed the mechanical properties of peripheral and nuclear regions of NIH-3T3 cells on azopolymer substrates with different topographic patterns. Micrometer scale patterns in the form of parallel ridges or square lattices of surface elevations were encoded on light responsive azopolymer films by means of contactless optical methods. Cell mechanics was investigated by atomic force microscopy (AFM). Cells and consequently the cell cytoskeleton were oriented along the linear patterns affecting cytoskeletal structures, e.g., formation of actin stress fibers. Our data demonstrate that topographic substrate patterns are recognized by cells and mechanical information is transferred by the cytoskeleton. Furthermore, cytoskeleton generated forces deform the nucleus, changing its morphology that appears to be related to different mechanical properties in the nuclear region.

Evaluation of dynamic elasticity module in samples of Portland (type 1) cement paste exposed to neutronic irradiation

International Nuclear Information System (INIS)

Rosa Junior, A.A.; Lucki, G.

1986-01-01

The fast neutron radiation effects and temperature on Portland cement are studied. The Dynamic Elasticity Module (Ed) in samples of Portland cement paste was evaluated. Ultrassonic technics were applied (resonance frequency and pulse velocity). The samples were irradiated with fast neutrons to fluence of 7,2 x 10 18 n/cm 2 (E approx. 1 MeV), at temperature of 120 + - 5 0 C, due to gamma heating. This temperature was simulated in laboratory in a microwave oven. (Author) [pt

Mg2+ in the major groove modulates B-DNA structure and dynamics.

Directory of Open Access Journals (Sweden)

Marc Guéroult

Full Text Available This study investigates the effect of Mg(2+ bound to the DNA major groove on DNA structure and dynamics. The analysis of a comprehensive dataset of B-DNA crystallographic structures shows that divalent cations are preferentially located in the DNA major groove where they interact with successive bases of (A/GpG and the phosphate group of 5'-CpA or TpG. Based on this knowledge, molecular dynamics simulations were carried out on a DNA oligomer without or with Mg(2+ close to an ApG step. These simulations showed that the hydrated Mg(2+ forms a stable intra-strand cross-link between the two purines in solution. ApG generates an electrostatic potential in the major groove that is particularly attractive for cations; its intrinsic conformation is well-adapted to the formation of water-mediated hydrogen bonds with Mg(2+. The binding of Mg(2+ modulates the behavior of the 5'-neighboring step by increasing the BII (ε-ζ>0° population of its phosphate group. Additional electrostatic interactions between the 5'-phosphate group and Mg(2+ strengthen both the DNA-cation binding and the BII character of the 5'-step. Cation binding in the major groove may therefore locally influence the DNA conformational landscape, suggesting a possible avenue for better understanding how strong DNA distortions can be stabilized in protein-DNA complexes.

Trajectory optimization for dynamic couch rotation during volumetric modulated arc radiotherapy

Science.gov (United States)

Smyth, Gregory; Bamber, Jeffrey C.; Evans, Philip M.; Bedford, James L.

2013-11-01

Non-coplanar radiation beams are often used in three-dimensional conformal and intensity modulated radiotherapy to reduce dose to organs at risk (OAR) by geometric avoidance. In volumetric modulated arc radiotherapy (VMAT) non-coplanar geometries are generally achieved by applying patient couch rotations to single or multiple full or partial arcs. This paper presents a trajectory optimization method for a non-coplanar technique, dynamic couch rotation during VMAT (DCR-VMAT), which combines ray tracing with a graph search algorithm. Four clinical test cases (partial breast, brain, prostate only, and prostate and pelvic nodes) were used to evaluate the potential OAR sparing for trajectory-optimized DCR-VMAT plans, compared with standard coplanar VMAT. In each case, ray tracing was performed and a cost map reflecting the number of OAR voxels intersected for each potential source position was generated. The least-cost path through the cost map, corresponding to an optimal DCR-VMAT trajectory, was determined using Dijkstra’s algorithm. Results show that trajectory optimization can reduce dose to specified OARs for plans otherwise comparable to conventional coplanar VMAT techniques. For the partial breast case, the mean heart dose was reduced by 53%. In the brain case, the maximum lens doses were reduced by 61% (left) and 77% (right) and the globes by 37% (left) and 40% (right). Bowel mean dose was reduced by 15% in the prostate only case. For the prostate and pelvic nodes case, the bowel V50 Gy and V60 Gy were reduced by 9% and 45% respectively. Future work will involve further development of the algorithm and assessment of its performance over a larger number of cases in site-specific cohorts.

Dynamic Circadian Modulation in a Biomathematical Model for the Effects of Sleep and Sleep Loss on Waking Neurobehavioral Performance

Science.gov (United States)

McCauley, Peter; Kalachev, Leonid V.; Mollicone, Daniel J.; Banks, Siobhan; Dinges, David F.; Van Dongen, Hans P. A.

2013-01-01

Recent experimental observations and theoretical advances have indicated that the homeostatic equilibrium for sleep/wake regulation—and thereby sensitivity to neurobehavioral impairment from sleep loss—is modulated by prior sleep/wake history. This phenomenon was predicted by a biomathematical model developed to explain changes in neurobehavioral performance across days in laboratory studies of total sleep deprivation and sustained sleep restriction. The present paper focuses on the dynamics of neurobehavioral performance within days in this biomathematical model of fatigue. Without increasing the number of model parameters, the model was updated by incorporating time-dependence in the amplitude of the circadian modulation of performance. The updated model was calibrated using a large dataset from three laboratory experiments on psychomotor vigilance test (PVT) performance, under conditions of sleep loss and circadian misalignment; and validated using another large dataset from three different laboratory experiments. The time-dependence of circadian amplitude resulted in improved goodness-of-fit in night shift schedules, nap sleep scenarios, and recovery from prior sleep loss. The updated model predicts that the homeostatic equilibrium for sleep/wake regulation—and thus sensitivity to sleep loss—depends not only on the duration but also on the circadian timing of prior sleep. This novel theoretical insight has important implications for predicting operator alertness during work schedules involving circadian misalignment such as night shift work. Citation: McCauley P; Kalachev LV; Mollicone DJ; Banks S; Dinges DF; Van Dongen HPA. Dynamic circadian modulation in a biomathematical model for the effects of sleep and sleep loss on waking neurobehavioral performance. SLEEP 2013;36(12):1987-1997. PMID:24293775

Dynamic modulation of thymidylate synthase gene expression and fluorouracil sensitivity in human colorectal cancer cells.

Directory of Open Access Journals (Sweden)

Kentaro Wakasa

Full Text Available Biomarkers have revolutionized cancer chemotherapy. However, many biomarker candidates are still in debate. In addition to clinical studies, a priori experimental approaches are needed. Thymidylate synthase (TS expression is a long-standing candidate as a biomarker for 5-fluorouracil (5-FU treatment of cancer patients. Using the Tet-OFF system and a human colorectal cancer cell line, DLD-1, we first constructed an in vitro system in which TS expression is dynamically controllable. Quantitative assays have elucidated that TS expression in the transformant was widely modulated, and that the dynamic range covered 15-fold of the basal level. 5-FU sensitivity of the transformant cells significantly increased in response to downregulated TS expression, although being not examined in the full dynamic range because of the doxycycline toxicity. Intriguingly, our in vitro data suggest that there is a linear relationship between TS expression and the 5-FU sensitivity in cells. Data obtained in a mouse model using transformant xenografts were highly parallel to those obtained in vitro. Thus, our in vitro and in vivo observations suggest that TS expression is a determinant of 5-FU sensitivity in cells, at least in this specific genetic background, and, therefore, support the possibility of TS expression as a biomarker for 5-FU-based cancer chemotherapy.

Dynamics of the spectrum of a self-modulated powerful laser pulse in an underdense plasma

International Nuclear Information System (INIS)

Andreev, N.E.; Kirsanov, V.I.; Sakharov, A.S.

1997-01-01

The evolution of the spectrum of a powerful laser pulse during its self-modulation in an underdense plasma is studied analytically and numerically. It is shown that, in the early stages of the self-modulation instability, the linear theory gives a qualitatively correct description of the dynamics of the pulse spectrum in most cases. Depending on the parameters of the laser pulse and of the plasma, this spectrum contains either Stocks satellites (downshifted from the fundamental frequency to a value equal to the plasma frequency), or both Stocks and anti-Stocks satellites of the fundamental frequency. When the three-dimensional mechanism for the instability is dominant and the pulse power is close to the critical power for relativistic self-focusing, the numerical calculations show that the intensity of the blue satellite exceeds the intensity of the red one. This specific feature of the spectrum, which does not arise when the instability is one-dimensional, cannot be explained in terms of the linear para-axial theory, and can be used to identify the three-dimensional mechanism for the instability in experiments on the self-modulation of powerful laser pulses. It is shown that the transition to the nonlinear stage of the instability is accompanied by the occurrence of cascades (at frequencies separated from the laser carrier frequency by intervals equal to an integer number of plasma frequencies) in the spectrum of the laser pulse

Microsoft Dynamics GP 2013 financial management

CERN Document Server

Grieve, Ian

2013-01-01

A standard tutorial-based approach covering Microsoft Dynamics GP 2013 and its six financial modules. The book is intended to allow users to improve their system use and workflow by introducing new modules to assist in financial management.This book is for you if you're a Dynamics GP partner, or Dynamics GP user, primarily focused on delivering application optimizations. This book assumes that you have a working knowledge of Microsoft Dynamics GP and have an understanding of the requirements of financial management.

Two-Dimensional SiO2/VO2 Photonic Crystals with Statically Visible and Dynamically Infrared Modulated for Smart Window Deployment.

Science.gov (United States)

Ke, Yujie; Balin, Igal; Wang, Ning; Lu, Qi; Tok, Alfred Iing Yoong; White, Timothy J; Magdassi, Shlomo; Abdulhalim, Ibrahim; Long, Yi

2016-12-07

Two-dimensional (2D) photonic structures, widely used for generating photonic band gaps (PBG) in a variety of materials, are for the first time integrated with the temperature-dependent phase change of vanadium dioxide (VO 2 ). VO 2 possesses thermochromic properties, whose potential remains unrealized due to an undesirable yellow-brown color. Here, a SiO 2 /VO 2 core/shell 2D photonic crystal is demonstrated to exhibit static visible light tunability and dynamic near-infrared (NIR) modulation. Three-dimensional (3D) finite difference time domain (FDTD) simulations predict that the transmittance can be tuned across the visible spectrum, while maintaining good solar regulation efficiency (ΔT sol = 11.0%) and high solar transmittance (T lum = 49.6%). Experiments show that the color changes of VO 2 films are accompanied by NIR modulation. This work presents a novel way to manipulate VO 2 photonic structures to modulate light transmission as a function of wavelength at different temperatures.

One- and two-dimensional gap solitons and dynamics in the PT-symmetric lattice potential and spatially-periodic momentum modulation

Science.gov (United States)

Chen, Yong; Yan, Zhenya; Li, Xin

2018-02-01

The influence of spatially-periodic momentum modulation on beam dynamics in parity-time (PT) symmetric optical lattice is systematically investigated in the one- and two-dimensional nonlinear Schrödinger equations. In the linear regime, we demonstrate that the momentum modulation can alter the first and second PT thresholds of the classical lattice, periodically or regularly change the shapes of the band structure, rotate and split the diffraction patterns of beams leading to multiple refraction and emissions. In the Kerr-nonlinear regime for one-dimension (1D) case, a large family of fundamental solitons within the semi-infinite gap can be found to be stable, even beyond the second PT threshold; it is shown that the momentum modulation can shrink the existing range of fundamental solitons and not change their stability. For two-dimension (2D) case, most solitons with higher intensities are relatively unstable in their existing regions which are narrower than those in 1D case, but we also find stable fundamental solitons corroborated by linear stability analysis and direct beam propagation. More importantly, the momentum modulation can also utterly change the direction of the transverse power flow and control the energy exchange among gain or loss regions.

Integrin β1 regulates leiomyoma cytoskeletal integrity and growth

Science.gov (United States)

Malik, Minnie; Segars, James; Catherino, William H.

2014-01-01

Uterine leiomyomas are characterized by an excessive extracellular matrix, increased mechanical stress, and increased active RhoA. Previously, we observed that mechanical signaling was attenuated in leiomyoma, but the mechanisms responsible remain unclear. Integrins, especially integrin β1, are transmembrane adhesion receptors that couple extracellular matrix stresses to the intracellular cytoskeleton to influence cell proliferation and differentiation. Here we characterized integrin and laminin to signaling in leiomyoma cells. We observed a 2.25 ± 0.32 fold increased expression of integrin β1 in leiomyoma cells, compared to myometrial cells. Antibody-mediated inhibition of integrin β1 led to significant growth inhibition in leiomyoma cells and a loss of cytoskeletal integrity. Specifically, polymerization of actin filaments and formation of focal adhesions were reduced by inhibition of integrin p1. Inhibition of integrin β1 in leiomyoma cells led to 0.81 ± 0.02 fold decrease in active RhoA, and resembled levels found in serum-starved cells. Likewise, inhibition of integrin β1 was accompanied by a decrease in phospho-ERK. Compared to myometrial cells, leiomyoma cells demonstrated increased expression of integrin α6 subunit to laminin receptor (1.91 ± 0.11 fold), and increased expression of laminin 5α (1.52±0.02), laminin 5β (3.06±0.92), and laminin 5γ (1.66 ± 0.06). Of note, leiomyoma cells grown on laminin matrix appear to realign themselves. Taken together, the findings reveal that the attenuated mechanical signaling in leiomyoma cells is accompanied by an increased expression and a dependence on integrin β1 signaling in leiomyoma cells, compared to myometrial cells. PMID:23023061

Solar dynamic power systems for space station

Science.gov (United States)

Irvine, Thomas B.; Nall, Marsha M.; Seidel, Robert C.

1986-01-01

The Parabolic Offset Linearly Actuated Reflector (POLAR) solar dynamic module was selected as the baseline design for a solar dynamic power system aboard the space station. The POLAR concept was chosen over other candidate designs after extensive trade studies. The primary advantages of the POLAR concept are the low mass moment of inertia of the module about the transverse boom and the compactness of the stowed module which enables packaging of two complete modules in the Shuttle orbiter payload bay. The fine pointing control system required for the solar dynamic module has been studied and initial results indicate that if disturbances from the station are allowed to back drive the rotary alpha joint, pointing errors caused by transient loads on the space station can be minimized. This would allow pointing controls to operate in bandwidths near system structural frequencies. The incorporation of the fine pointing control system into the solar dynamic module is fairly straightforward for the three strut concentrator support structure. However, results of structural analyses indicate that this three strut support is not optimum. Incorporation of a vernier pointing system into the proposed six strut support structure is being studied.

Location of and post-mortem changes in some cytoskeletal proteins in pork and cod muscle

DEFF Research Database (Denmark)

Morrison, E.H.; Bremner, Allan; Purslow, P.P.

2000-01-01

The cytoskeletal proteins actin, nebulin, spectrin, desmin, vinculin and talin were labelled immunohistochemically in sections of muscle from commercially available pigs and cod (Gadus morhua) taken pre-rigor and from samples stored for several days. Actin, nebulin and spectrin gave similar...... labelling patterns in both pork and cod muscle which remained the same in stored samples. Desmin was intensely labelled at the cell boundaries and within the body of the cells in both pork and cod in the initial and the stored samples. Vinculin was readily labelled in pork muscle but showed only diffuse...... labelling in fish. Labelling for talin in pork muscle was intense at the sarcolemma but was not present in samples stored for 4 days. In contrast, the label for talin was concentrated at the myotendinous junction of the cod muscle throughout the storage period. These are the first reports of the detection...

Dynamics robustness of cascading systems.

Directory of Open Access Journals (Sweden)

Jonathan T Young

2017-03-01

Full Text Available A most important property of biochemical systems is robustness. Static robustness, e.g., homeostasis, is the insensitivity of a state against perturbations, whereas dynamics robustness, e.g., homeorhesis, is the insensitivity of a dynamic process. In contrast to the extensively studied static robustness, dynamics robustness, i.e., how a system creates an invariant temporal profile against perturbations, is little explored despite transient dynamics being crucial for cellular fates and are reported to be robust experimentally. For example, the duration of a stimulus elicits different phenotypic responses, and signaling networks process and encode temporal information. Hence, robustness in time courses will be necessary for functional biochemical networks. Based on dynamical systems theory, we uncovered a general mechanism to achieve dynamics robustness. Using a three-stage linear signaling cascade as an example, we found that the temporal profiles and response duration post-stimulus is robust to perturbations against certain parameters. Then analyzing the linearized model, we elucidated the criteria of when signaling cascades will display dynamics robustness. We found that changes in the upstream modules are masked in the cascade, and that the response duration is mainly controlled by the rate-limiting module and organization of the cascade's kinetics. Specifically, we found two necessary conditions for dynamics robustness in signaling cascades: 1 Constraint on the rate-limiting process: The phosphatase activity in the perturbed module is not the slowest. 2 Constraints on the initial conditions: The kinase activity needs to be fast enough such that each module is saturated even with fast phosphatase activity and upstream changes are attenuated. We discussed the relevance of such robustness to several biological examples and the validity of the above conditions therein. Given the applicability of dynamics robustness to a variety of systems, it

Externally induced frontoparietal synchronization modulates network dynamics and enhances working memory performance.

Science.gov (United States)

Violante, Ines R; Li, Lucia M; Carmichael, David W; Lorenz, Romy; Leech, Robert; Hampshire, Adam; Rothwell, John C; Sharp, David J

2017-03-14

Cognitive functions such as working memory (WM) are emergent properties of large-scale network interactions. Synchronisation of oscillatory activity might contribute to WM by enabling the coordination of long-range processes. However, causal evidence for the way oscillatory activity shapes network dynamics and behavior in humans is limited. Here we applied transcranial alternating current stimulation (tACS) to exogenously modulate oscillatory activity in a right frontoparietal network that supports WM. Externally induced synchronization improved performance when cognitive demands were high. Simultaneously collected fMRI data reveals tACS effects dependent on the relative phase of the stimulation and the internal cognitive processing state. Specifically, synchronous tACS during the verbal WM task increased parietal activity, which correlated with behavioral performance. Furthermore, functional connectivity results indicate that the relative phase of frontoparietal stimulation influences information flow within the WM network. Overall, our findings demonstrate a link between behavioral performance in a demanding WM task and large-scale brain synchronization.

Modifications and applications of DSNP-modules to the THTR-300 steamgenerators

International Nuclear Information System (INIS)

Sokcic-Kostic, M.; Scherer, W.

1991-01-01

The DSNP System (Dynamic Simulator for Nuclear Power Plants) is being used for describing of the dynamic behaviour of the THTR-300 high temperature reactor power plant. Three different models of steam generators of different degree of sophistication have been examined and compared. The calculation of steam properties was changed to a fast table-lookup mode and several errors in the computational modules are eliminated. In one of the steam generator modules the capability of using helium on the primary side was newly implemented. The comparison of the modules showed that the most elaborated module gives detailed results close to the reality. For fast overview calculations the simplest module can be used satisfactorily. (author)

Creep Burst Testing of a Woven Inflatable Module

Science.gov (United States)

Selig, Molly M.; Valle, Gerard D.; James, George H.; Oliveras, Ovidio M.; Jones, Thomas C.; Doggett, William R.

2015-01-01

A woven Vectran inflatable module 88 inches in diameter and 10 feet long was tested at the NASA Johnson Space Center until failure from creep. The module was pressurized pneumatically to an internal pressure of 145 psig, and was held at pressure until burst. The external environment remained at standard atmospheric temperature and pressure. The module burst occurred after 49 minutes at the target pressure. The test article pressure and temperature were monitored, and video footage of the burst was captured at 60 FPS. Photogrammetry was used to obtain strain measurements of some of the webbing. Accelerometers on the test article measured the dynamic response. This paper discusses the test article, test setup, predictions, observations, photogrammetry technique and strain results, structural dynamics methods and quick-look results, and a comparison of the module level creep behavior to the strap level creep behavior.

A Monte Carlo dosimetric quality assurance system for dynamic intensity-modulated radiotherapy

International Nuclear Information System (INIS)

Takegawa, Hideki; Yamamoto, Tokihiro; Miyabe, Yuki; Teshima, Teruki; Kunugi, Tomoaki; Yano, Shinsuke; Mizowaki, Takashi; Nagata, Yasushi; Hiraoka, Masahiro

2005-01-01

We are developing a Monte Carlo (MC) dose calculation system, which can resolve dosimetric issues derived from multileaf collimator (MLC) design for routine dosimetric quality assurance (QA) of intensity-modulated radiotherapy (IMRT). The treatment head of the medical linear accelerator equipped with MLC was modeled using the EGS4 MC code. A graphical user interface (GUI) application was developed to implement MC dose computation in the CT-based patient model and compare the MC calculated results with those of a commercial radiotherapy treatment planning (RTP) system, Varian Eclipse. To reduce computation time, the EGS4 MC code has been parallelized on massive parallel processing (MPP) system using the message passing interface (MPI). The MC treatment head model and MLC model were validated by the measurement data sets of percentage depth dose (PDD) and off-center ratio (OCR) in the water phantom and the film measurements for the static and dynamic test patterns, respectively. In the treatment head model, the MC calculated results agreed with those of measurements for both of PDD and OCR. The MC could reproduce all of the MLC dosimetric effects. A quantitative comparison between the results of MC and Eclipse was successfully performed with the GUI application. Parallel speed-up became almost linear. An MC dosimetric QA system for dynamic IMRT has been developed, however there were large dose discrepancies between the MC and the measurement in the MLC model simulation, which are now being investigated. (author)

Segmental and dynamic intensity-modulated radiotherapy delivery techniques for micro-multileaf collimator

International Nuclear Information System (INIS)

Agazaryan, Nzhde; Solberg, Timothy D.

2003-01-01

A leaf sequencing algorithm has been implemented to deliver segmental and dynamic multileaf collimated intensity-modulated radiotherapy (SMLC-IMRT and DMLC-IMRT, respectively) using a linear accelerator equipped with a micro-multileaf collimator (mMLC). The implementation extends a previously published algorithm for the SMLC-IMRT to include the dynamic MLC-IMRT method and several dosimetric considerations. The algorithm has been extended to account for the transmitted radiation and minimize the leakage between opposing and neighboring leaves. The underdosage problem associated with the tongue-and-groove design of the MLC is significantly reduced by synchronizing the MLC leaf movements. The workings of the leaf sequencing parameters have been investigated and the results of the planar dosimetric investigations show that the sequencing parameters affect the measured dose distributions as intended. Investigations of clinical cases suggest that SMLC and DMLC delivery methods produce comparable results with leaf sequences obtained by root-mean-square (RMS) errors specification of 1.5% and lower, approximately corresponding to 20 or more segments. For SMLC-IMRT, there is little to be gained by using an RMS error specification smaller than 2%, approximately corresponding to 15 segments; however, more segments directly translate to longer treatment time and more strain on the MLC. The implemented leaf synchronization method does not increase the required monitor units while it reduces the measured TG underdoses from a maximum of 12% to a maximum of 3% observed with single field measurements of representative clinical cases studied

High-speed three-dimensional shape measurement for dynamic scenes using bi-frequency tripolar pulse-width-modulation fringe projection

Science.gov (United States)

Zuo, Chao; Chen, Qian; Gu, Guohua; Feng, Shijie; Feng, Fangxiaoyu; Li, Rubin; Shen, Guochen

2013-08-01

This paper introduces a high-speed three-dimensional (3-D) shape measurement technique for dynamic scenes by using bi-frequency tripolar pulse-width-modulation (TPWM) fringe projection. Two wrapped phase maps with different wavelengths can be obtained simultaneously by our bi-frequency phase-shifting algorithm. Then the two phase maps are unwrapped using a simple look-up-table based number-theoretical approach. To guarantee the robustness of phase unwrapping as well as the high sinusoidality of projected patterns, TPWM technique is employed to generate ideal fringe patterns with slight defocus. We detailed our technique, including its principle, pattern design, and system setup. Several experiments on dynamic scenes were performed, verifying that our method can achieve a speed of 1250 frames per second for fast, dense, and accurate 3-D measurements.

An abstract machine for module replacement

OpenAIRE

Walton, Chris; Krl, Dilsun; Gilmore, Stephen

1998-01-01

In this paper we define an abstract machine model for the mλ typed intermediate language. This abstract machine is used to give a formal description of the operation of run-time module replacement from the programming language Dynamic ML. The essential technical device which we employ for module replacement is a modification of two-space copying garbage collection.

Dynamic photosynthesis in different environmental conditions.

Science.gov (United States)

Kaiser, Elias; Morales, Alejandro; Harbinson, Jeremy; Kromdijk, Johannes; Heuvelink, Ep; Marcelis, Leo F M

2015-05-01

Incident irradiance on plant leaves often fluctuates, causing dynamic photosynthesis. Whereas steady-state photosynthetic responses to environmental factors have been extensively studied, knowledge of dynamic modulation of photosynthesis remains scarce and scattered. This review addresses this discrepancy by summarizing available data and identifying the research questions necessary to advance our understanding of interactions between environmental factors and dynamic behaviour of photosynthesis using a mechanistic framework. Firstly, dynamic photosynthesis is separated into sub-processes related to proton and electron transport, non-photochemical quenching, control of metabolite flux through the Calvin cycle (activation states of Rubisco and RuBP regeneration, and post-illumination metabolite turnover), and control of CO₂ supply to Rubisco (stomatal and mesophyll conductance changes). Secondly, the modulation of dynamic photosynthesis and its sub-processes by environmental factors is described. Increases in ambient CO₂ concentration and temperature (up to ~35°C) enhance rates of photosynthetic induction and decrease its loss, facilitating more efficient dynamic photosynthesis. Depending on the sensitivity of stomatal conductance, dynamic photosynthesis may additionally be modulated by air humidity. Major knowledge gaps exist regarding environmental modulation of loss of photosynthetic induction, dynamic changes in mesophyll conductance, and the extent of limitations imposed by stomatal conductance for different species and environmental conditions. The study of mutants or genetic transformants for specific processes under various environmental conditions could provide significant progress in understanding the control of dynamic photosynthesis. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Effect of collagen I and fibronectin on the adhesion, elasticity and cytoskeletal organization of prostate cancer cells

Energy Technology Data Exchange (ETDEWEB)

Docheva, Denitsa [Experimental Surgery and Regenerative Medicine, Department of Surgery, Ludwig-Maximilians-University (LMU), Nussbaumstr. 20, 80336 Munich (Germany); Padula, Daniela [Experimental Surgery and Regenerative Medicine, Department of Surgery, Ludwig-Maximilians-University (LMU), Nussbaumstr. 20, 80336 Munich (Germany); Department of Precision- and Micro-Engineering, Engineering Physics, Munich University of Applied Sciences, Lothstr. 34, 80335 Munich (Germany); Center for NanoScience (CeNS), Geschwister-Scholl-Platz 1, 80539 Munich (Germany); Schieker, Matthias, E-mail: matthias.schieker@med.uni-muenchen.de [Experimental Surgery and Regenerative Medicine, Department of Surgery, Ludwig-Maximilians-University (LMU), Nussbaumstr. 20, 80336 Munich (Germany); Clausen-Schaumann, Hauke, E-mail: clausen-schaumann@hm.edu [Department of Precision- and Micro-Engineering, Engineering Physics, Munich University of Applied Sciences, Lothstr. 34, 80335 Munich (Germany); Center for NanoScience (CeNS), Geschwister-Scholl-Platz 1, 80539 Munich (Germany)

2010-11-12

Research highlights: {yields} Depending on the metastatic origin, prostate cancer cells differ in their affinity to COL1. {yields} COL1 affects specifically the F-actin and cell elasticity of bone-derived prostate cancer cells. {yields} Cell elasticity can be used as a biomarker for cancer cells from different metastases. -- Abstract: Despite of intensive research efforts, the precise mechanism of prostate cancer metastasis in bone is still not fully understood. Several studies have suggested that specific matrix production by the bone cells, such as collagen I, supports cancer cell invasion. The aim of this study was to investigate the effect of collagen I (COL1) and fibronectin (FN) on cell adhesion, cell elasticity and cytoskeletal organization of prostate cancer cells. Two cell lines, bone marrow- (PC3) and lymph node-derived (LNCaP) were cultivated on COL1 and FN (control protein). By using a quantitative adhesion assay and time-lapse analysis, it was found that PC3, but not LNCaP, adhered strongly and were more spread on COL1. Next, PC3 and LNCaP were evaluated by atomic force microscopy (AFM) and flatness shape factor and cellular Young's modulus were calculated. The shape analysis revealed that PC3 were significantly flatter when grown on COL1 in comparison to LNCaP. In general, PC3 were also significantly stiffer than LNCaP and furthermore, their stiffness increased upon interaction with COL1. Since cell stiffness is strongly dependent on actin organization, phalloidin-based actin staining was performed and revealed that, of the two cell types as well as the two different matrix proteins, only PC3 grown on COL1 formed robust actin cytoskeleton. In conclusion, our study showed that PC3 cells have a strong affinity towards COL1. On this matrix protein, the cells adhered strongly and underwent a specific cell flattening. Moreover, with the establishment of PC3 contact to COL1 a significant increase of PC3 stiffness was observed due to a profound

A novel system of cytoskeletal elements in the human pathogen Helicobacter pylori.

Directory of Open Access Journals (Sweden)

Barbara Waidner

2009-11-01

Full Text Available Pathogenicity of the human pathogen Helicobacter pylori relies upon its capacity to adapt to a hostile environment and to escape from the host response. Therefore, cell shape, motility, and pH homeostasis of these bacteria are specifically adapted to the gastric mucus. We have found that the helical shape of H. pylori depends on coiled coil rich proteins (Ccrp, which form extended filamentous structures in vitro and in vivo, and are differentially required for the maintenance of cell morphology. We have developed an in vivo localization system for this pathogen. Consistent with a cytoskeleton-like structure, Ccrp proteins localized in a regular punctuate and static pattern within H. pylori cells. Ccrp genes show a high degree of sequence variation, which could be the reason for the morphological diversity between H. pylori strains. In contrast to other bacteria, the actin-like MreB protein is dispensable for viability in H. pylori, and does not affect cell shape, but cell length and chromosome segregation. In addition, mreB mutant cells displayed significantly reduced urease activity, and thus compromise a major pathogenicity factor of H. pylori. Our findings reveal that Ccrp proteins, but not MreB, affect cell morphology, while both cytoskeletal components affect the development of pathogenicity factors and/or cell cycle progression.

The cytoskeletal inhibitors latrunculin A and blebbistatin exert antitumorigenic properties in human hepatocellular carcinoma cells by interfering with intracellular HuR trafficking

Energy Technology Data Exchange (ETDEWEB)

Doller, Anke; Badawi, Amel [Pharmazentrum Frankfurt/ZAFES, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Schmid, Tobias; Brauß, Thilo [Institut für Biochemie I (Pathobiochemie), Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Pleli, Thomas [Medizinische Klinik 1, Schwerpunkt Gastroenterologie und Hepatologie, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Meyer zu Heringdorf, Dagmar [Pharmazentrum Frankfurt/ZAFES, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Piiper, Albrecht [Medizinische Klinik 1, Schwerpunkt Gastroenterologie und Hepatologie, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Pfeilschifter, Josef [Pharmazentrum Frankfurt/ZAFES, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Eberhardt, Wolfgang, E-mail: w.eberhardt@em.uni-frankfurt.de [Pharmazentrum Frankfurt/ZAFES, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany)

2015-01-01

The impact of the RNA-binding protein HuR for the post-transcriptional deregulation of tumor-relevant genes is well established. Despite of elevations in HuR expression levels, an increase in cytoplasmic HuR abundance in many cases correlates with a high grade of malignancy. Here, we demonstrated that administration of the actin-depolymerizing macrolide latrunculin A, or blebbistatin, an inhibitor of myosin II ATPase activity, caused a dose- and time-dependent reduction in the high cytoplasmic HuR content of HepG2 and Huh7 hepatocellular carcinoma (HCC) cells. Subcellular fractionation revealed that in addition, both inhibitors strongly attenuated cytoskeletal and membrane-bound HuR abundance and conversely increased the HuR amount in nuclear cell fractions. Concomitant with changes in intracellular HuR localization, both cytoskeletal inhibitors markedly decreased the half-lives of cyclooxygenase-2 (COX-2), cyclin A and cyclin D{sub 1} encoding mRNAs resulting in a significant reduction in their expression levels in HepG2 cells. Importantly, a similar reduction in the expression of these HuR targets was achieved by a RNA interference (RNAi)-mediated knockdown of either HuR or nonmuscle myoin IIA. Using polysomal fractionation, we further demonstrate that the decrease in cytoplasmic HuR by latrunculin A or blebbistatin is accompanied by a marked change in the allocation of HuR and its mRNA cargo from polysomes to ribonucleoprotein (RNP) particles. Functionally, the basal migration and prostaglandin E{sub 2} synthesis are similarly impaired in inhibitor-treated and stable HuR-knockdown HepG2 cells. Our data demonstrate that interfering with the actomyosin-dependent HuR trafficking may comprise a valid therapeutic option for antagonizing pathologic posttranscriptional gene expression by HuR and furthermore emphasize the potential benefit of HuR inhibitory strategies for treatment of HCC. - Highlights: • We tested the effects of latrunculin A and blebbistatin on

Optically Modulated Multiband Terahertz Perfect Absorber

DEFF Research Database (Denmark)

Seren, Huseyin R.; Keiser, George R.; Cao, Lingyue

2014-01-01

response of resonant metamaterials continues to be a challengingendeavor. Resonant perfect absorbers have flourished as one of the mostpromising metamaterial devices with applications ranging from power har-vesting to terahertz imaging. Here, an optically modulated resonant perfectabsorber is presented....... Utilizing photo-excited free carriers in silicon padsplaced in the capacitive gaps of split ring resonators, a dynamically modu-lated perfect absorber is designed and fabricated to operate in reflection.Large modulation depth (38% and 91%) in two absorption bands (with 97%and 92% peak absorption...

Cellular adhesome screen identifies critical modulators of focal adhesion dynamics, cellular traction forces and cell migration behaviour

Science.gov (United States)

Fokkelman, Michiel; Balcıoğlu, Hayri E.; Klip, Janna E.; Yan, Kuan; Verbeek, Fons J.; Danen, Erik H. J.; van de Water, Bob

2016-01-01

Cancer cells migrate from the primary tumour into surrounding tissue in order to form metastasis. Cell migration is a highly complex process, which requires continuous remodelling and re-organization of the cytoskeleton and cell-matrix adhesions. Here, we aimed to identify genes controlling aspects of tumour cell migration, including the dynamic organization of cell-matrix adhesions and cellular traction forces. In a siRNA screen targeting most cell adhesion-related genes we identified 200+ genes that regulate size and/or dynamics of cell-matrix adhesions in MCF7 breast cancer cells. In a subsequent secondary screen, the 64 most effective genes were evaluated for growth factor-induced cell migration and validated by tertiary RNAi pool deconvolution experiments. Four validated hits showed significantly enlarged adhesions accompanied by reduced cell migration upon siRNA-mediated knockdown. Furthermore, loss of PPP1R12B, HIPK3 or RAC2 caused cells to exert higher traction forces, as determined by traction force microscopy with elastomeric micropillar post arrays, and led to considerably reduced force turnover. Altogether, we identified genes that co-regulate cell-matrix adhesion dynamics and traction force turnover, thereby modulating overall motility behaviour. PMID:27531518

Dosimetric verification for primary focal hypermetabolism of nasopharyngeal carcinoma patients treated with dynamic intensity-modulated radiation therapy.

Science.gov (United States)

Xin, Yong; Wang, Jia-Yang; Li, Liang; Tang, Tian-You; Liu, Gui-Hong; Wang, Jian-She; Xu, Yu-Mei; Chen, Yong; Zhang, Long-Zhen

2012-01-01

To make sure the feasibility with (18F)FDG PET/CT to guided dynamic intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma patients, by dosimetric verification before treatment. Chose 11 patients in III~IVA nasopharyngeal carcinoma treated with functional image-guided IMRT and absolute and relative dosimetric verification by Varian 23EX LA, ionization chamber, 2DICA of I'mRT Matrixx and IBA detachable phantom. Drawing outline and making treatment plan were by different imaging techniques (CT and (18F)FDG PET/CT). The dose distributions of the various regional were realized by SMART. The absolute mean errors of interest area were 2.39%±0.66 using 0.6 cc ice chamber. Results using DTA method, the average relative dose measurements within our protocol (3%, 3 mm) were 87.64% at 300 MU/min in all filed. Dosimetric verification before IMRT is obligatory and necessary. Ionization chamber and 2DICA of I'mRT Matrixx was the effective dosimetric verification tool for primary focal hyper metabolism in functional image-guided dynamic IMRT for nasopharyngeal carcinoma. Our preliminary evidence indicates that functional image-guided dynamic IMRT is feasible.

Chaotic Dynamics of a Josephson Junction with a Ratchet Potential and Current-Modulating Damping

Science.gov (United States)

Li, Fei; Li, Wenwu; Xu, Lan

2018-04-01

The chaotic dynamics of a Josephson junction with a ratchet potential and current-modulating damping are studied. Under the first-order approximation, we construct the general solution of the first-order equation whose boundedness condition contains the famous Melnikov chaotic criterion. Based on the general solution, the incomputability and unpredictability of the system's chaotic behavior are discussed. For the case beyond perturbation conditions, the evolution of stroboscopic Poincaré sections shows that the system undergoes a quasi-periodic transition to chaos with an increasing intensity of the rf-current. Through a suitable feedback controlling strategy, the chaos can be effectively suppressed and the intensity of the controller can vary in a large range. It is also found that the current between the two separated superconductors increases monotonously in some specific parameter spaces.

Modulations of 'late' event-related brain potentials in humans by dynamic audiovisual speech stimuli.

Science.gov (United States)

Lebib, Riadh; Papo, David; Douiri, Abdel; de Bode, Stella; Gillon Dowens, Margaret; Baudonnière, Pierre-Marie

2004-11-30

Lipreading reliably improve speech perception during face-to-face conversation. Within the range of good dubbing, however, adults tolerate some audiovisual (AV) discrepancies and lipreading, then, can give rise to confusion. We used event-related brain potentials (ERPs) to study the perceptual strategies governing the intermodal processing of dynamic and bimodal speech stimuli, either congruently dubbed or not. Electrophysiological analyses revealed that non-coherent audiovisual dubbings modulated in amplitude an endogenous ERP component, the N300, we compared to a 'N400-like effect' reflecting the difficulty to integrate these conflicting pieces of information. This result adds further support for the existence of a cerebral system underlying 'integrative processes' lato sensu. Further studies should take advantage of this 'N400-like effect' with AV speech stimuli to open new perspectives in the domain of psycholinguistics.

Dynamic e-learning modules for student lecture preparation

Directory of Open Access Journals (Sweden)

Timothy McIntyre

2018-03-01

Full Text Available We have developed and demonstrated the effectiveness of a set of online interactive learning modules to accompany physics courses at first- and second-year university levels. Students access the modules prior to attending lectures to familiarize themselves with content which is then discussed and reaffirmed in class. Student surveys and access data show that students were much more likely to use material presented in this form, rather than a textbook, when preparing for lectures given in an active learning format. The students found that interactive simulations, videos of problem-solving approaches prepared by course staff, and quick-check immediate feedback questions were all useful tools for lecture preparation–none of which are available when using a traditional textbook for lecture preparation.

Covalent modification of cytoskeletal proteins in neuronal cells by tryptamine-4,5-dione

Directory of Open Access Journals (Sweden)

Yoji Kato

2014-01-01

Full Text Available Serotonin, 5-hydroxytryptamine, is a systemic bioactive amine that acts in the gut and brain. As a substrate of myeloperoxidase in vitro, serotonin is oxidized to tryptamine-4,5-dione (TD, which is highly reactive with thiols. In this work, we successively prepared a monoclonal antibody to quinone-modified proteins and found that the antibody preferentially recognizes the TD–thiol adduct. Using the antibody, we observed that the chloride ion, the predominant physiological substrate for myeloperoxidase in vivo, is not competitive toward the enzyme catalyzed serotonin oxidation process, suggesting that serotonin is a plausible physiological substrate for the enzyme in vivo. Immunocytochemical analyses revealed that TD staining was observed in the cytosol of SH-SY5Y neuroblastoma cells while blot analyses showed that some cellular proteins were preferentially modified. Pull-down analyses confirmed that the cytoskeletal proteins tubulins, vimentin, and neurofilament-L were modified. When pure tubulins were exposed to micromolar levels of synthetic TD, self-polymerization was initially enhanced and then suppressed. These results suggest that serotonin oxidation by myeloperoxidase or the action of other oxidants could cause functional alteration of cellular proteins, which may be related to neurodegeneration processes or irritable bowel syndrome.

Mycoplasma pneumoniae cytoskeletal protein HMW2 and the architecture of the terminal organelle.

Science.gov (United States)

Bose, Stephanie R; Balish, Mitchell F; Krause, Duncan C

2009-11-01

The terminal organelle of Mycoplasma pneumoniae mediates cytadherence and gliding motility and functions in cell division. The defining feature of this complex membrane-bound cell extension is an electron-dense core of two segmented rods oriented longitudinally and enlarging to form a bulb at the distal end. While the components of the core have not been comprehensively identified, previous evidence suggested that the cytoskeletal protein HMW2 forms parallel bundles oriented lengthwise to yield the major rod of the core. In the present study, we tested predictions emerging from that model by ultrastructural and immunoelectron microscopy analyses of cores from wild-type M. pneumoniae and mutants producing HMW2 derivatives. Antibodies specific for the N or C terminus of HMW2 labeled primarily peripheral to the core along its entire length. Furthermore, truncation of HMW2 did not correlate specifically with core length. However, mutant analysis correlated specific HMW2 domains with core assembly, and examination of core-enriched preparations confirmed that HMW2 was a major component of these fractions. Taken together, these findings yielded a revised model for HMW2 in terminal organelle architecture.

Mycoplasma pneumoniae Cytoskeletal Protein HMW2 and the Architecture of the Terminal Organelle▿

Science.gov (United States)

Bose, Stephanie R.; Balish, Mitchell F.; Krause, Duncan C.

2009-01-01

The terminal organelle of Mycoplasma pneumoniae mediates cytadherence and gliding motility and functions in cell division. The defining feature of this complex membrane-bound cell extension is an electron-dense core of two segmented rods oriented longitudinally and enlarging to form a bulb at the distal end. While the components of the core have not been comprehensively identified, previous evidence suggested that the cytoskeletal protein HMW2 forms parallel bundles oriented lengthwise to yield the major rod of the core. In the present study, we tested predictions emerging from that model by ultrastructural and immunoelectron microscopy analyses of cores from wild-type M. pneumoniae and mutants producing HMW2 derivatives. Antibodies specific for the N or C terminus of HMW2 labeled primarily peripheral to the core along its entire length. Furthermore, truncation of HMW2 did not correlate specifically with core length. However, mutant analysis correlated specific HMW2 domains with core assembly, and examination of core-enriched preparations confirmed that HMW2 was a major component of these fractions. Taken together, these findings yielded a revised model for HMW2 in terminal organelle architecture. PMID:19717588

Title: Cytoskeletal proteins in cortical development and diseasesubtitle: Actin associated proteins in periventricular heterotopia

Directory of Open Access Journals (Sweden)

Gewei eLian

2015-04-01

Full Text Available The actin cytoskeleton regulates many important cellular processes in the brain, including cell division and proliferation, migration, and cytokinesis and differentiation. These developmental processes can be regulated through actin dependent vesicle and organelle movement, cell signaling, and the establishment and maintenance of cell junctions and cell shape. Many of these processes are mediated by extensive and intimate interactions of actin with cellular membranes and proteins. Disruption in the actin cytoskeleton in the brain gives rise to periventricular heterotopia (PH, a malformation of cortical development, characterized by abnormal neurons clustered deep in the brain along the lateral ventricles. This disorder can give rise to seizures, dyslexia and psychiatric disturbances. Anatomically, PH is characterized by a smaller brain (impaired proliferation, heterotopia (impaired initial migration and disruption along the neuroependymal lining (impaired cell-cell adhesion. Genes causal for PH have also been implicated in actin-dependent processes. The current review provides mechanistic insight into actin cytoskeletal regulation of cortical development in the context of this malformation of cortical development.

Rate modulation detection thresholds for cochlear implant users.

Science.gov (United States)

Brochier, Tim; McKay, Colette; McDermott, Hugh

2018-02-01

The perception of temporal amplitude modulations is critical for speech understanding by cochlear implant (CI) users. The present study compared the ability of CI users to detect sinusoidal modulations of the electrical stimulation rate and current level, at different presentation levels (80% and 40% of the dynamic range) and modulation frequencies (10 and 100 Hz). Rate modulation detection thresholds (RMDTs) and amplitude modulation detection thresholds (AMDTs) were measured and compared to assess whether there was a perceptual advantage to either modulation method. Both RMDTs and AMDTs improved with increasing presentation level and decreasing modulation frequency. RMDTs and AMDTs were correlated, indicating that a common processing mechanism may underlie the perception of rate modulation and amplitude modulation, or that some subject-dependent factors affect both types of modulation detection.

Spatial Terahertz Modulator

Science.gov (United States)

Xie, Zhenwei; Wang, Xinke; Ye, Jiasheng; Feng, Shengfei; Sun, Wenfeng; Akalin, Tahsin; Zhang, Yan

2013-11-01

Terahertz (THz) technology is a developing and promising candidate for biological imaging, security inspection and communications, due to the low photon energy, the high transparency and the broad band properties of the THz radiation. However, a major encountered bottleneck is lack of efficient devices to manipulate the THz wave, especially to modulate the THz wave front. A wave front modulator should allow the optical or electrical control of the spatial transmission (or reflection) of an input THz wave and hence the ability to encode the information in a wave front. Here we propose a spatial THz modulator (STM) to dynamically control the THz wave front with photo-generated carriers. A computer generated THz hologram is projected onto a silicon wafer by a conventional spatial light modulator (SLM). The corresponding photo-generated carrier spatial distribution will be induced, which forms an amplitude hologram to modulate the wave front of the input THz beam. Some special intensity patterns and vortex beams are generated by using this method. This all-optical controllable STM is structure free, high resolution and broadband. It is expected to be widely used in future THz imaging and communication systems.

Cardiac Exposure in the Dynamic Conformal Arc Therapy, Intensity-Modulated Radiotherapy and Volumetric Modulated Arc Therapy of Lung Cancer.

Directory of Open Access Journals (Sweden)

Xin Ming

Full Text Available To retrospectively evaluate the cardiac exposure in three cohorts of lung cancer patients treated with dynamic conformal arc therapy (DCAT, intensity-modulated radiotherapy (IMRT, or volumetric modulated arc therapy (VMAT at our institution in the past seven years.A total of 140 lung cancer patients were included in this institutional review board approved study: 25 treated with DCAT, 70 with IMRT and 45 with VMAT. All plans were generated in a same commercial treatment planning system and have been clinically accepted and delivered. The dose distribution to the heart and the effects of tumor laterality, the irradiated heart volume and the beam-to-heart distance on the cardiac exposure were investigated.The mean dose to the heart among all 140 plans was 4.5 Gy. Specifically, the heart received on average 2.3, 5.2 and 4.6 Gy in the DCAT, IMRT and VMAT plans, respectively. The mean heart doses for the left and right lung tumors were 4.1 and 4.8 Gy, respectively. No patients died with evidence of cardiac disease. Three patients (2% with preexisting cardiac condition developed cardiac disease after treatment. Furthermore, the cardiac exposure was found to increase linearly with the irradiated heart volume while decreasing exponentially with the beam-to-heart distance.Compared to old technologies for lung cancer treatment, modern radiotherapy treatment modalities demonstrated better heart sparing. But the heart dose in lung cancer radiotherapy is still higher than that in the radiotherapy of breast cancer and Hodgkin's disease where cardiac complications have been extensively studied. With strong correlations of mean heart dose with beam-to-heart distance and irradiated heart volume, cautions should be exercised to avoid long-term cardiac toxicity in the lung cancer patients undergoing radiotherapy.

Opto-electronic conversion logic behaviour through dynamic modulation of electron/energy transfer states at the TiO2-carbon quantum dot interface.

Science.gov (United States)

Wang, Fang; Zhang, Yonglai; Liu, Yang; Wang, Xuefeng; Shen, Mingrong; Lee, Shuit-Tong; Kang, Zhenhui

2013-03-07

Here we show a bias-mediated electron/energy transfer process at the CQDs-TiO(2) interface for the dynamic modulation of opto-electronic properties. Different energy and electron transfer states have been observed in the CQDs-TNTs system due to the up-conversion photoluminescence and the electron donation/acceptance properties of the CQDs decorated on TNTs.

Dosimetric and qualitative analysis of kinetic properties of millennium 80 multileaf collimator system for dynamic intensity modulated radiotherapy treatments

Directory of Open Access Journals (Sweden)

Bhardwaj Anup

2007-01-01

Full Text Available The aim of this paper is to analyze the positional accuracy, kinetic properties of the dynamic multileaf collimator (MLC and dosimetric evaluation of fractional dose delivery for the intensity modulated radiotherapy (IMRT for step and shoot and sliding window (dynamic techniques of Varian multileaf collimator millennium 80. Various quality assurance tests such as accuracy in leaf positioning and speed, stability of dynamic MLC output, inter and intra leaf transmission, dosimetric leaf separation and multiple carriage field verification were performed. Evaluation of standard field patterns as pyramid, peaks, wedge, chair, garden fence test, picket fence test and sweeping gap output was done. Patient dose quality assurance procedure consists of an absolute dose measurement for all fields at 5 cm depth on solid water phantom using 0.6cc water proof ion chamber and relative dose verification using Kodak EDR-2 films for all treatment fields along transverse and coronal direction using IMRT phantom. The relative dose verification was performed using Omni Pro IMRT film verification software. The tests performed showed acceptable results for commissioning the millennium 80 MLC and Clinac DHX for dynamic and step and shoot IMRT treatments.

Community landscapes: an integrative approach to determine overlapping network module hierarchy, identify key nodes and predict network dynamics.

Directory of Open Access Journals (Sweden)

István A Kovács

Full Text Available BACKGROUND: Network communities help the functional organization and evolution of complex networks. However, the development of a method, which is both fast and accurate, provides modular overlaps and partitions of a heterogeneous network, has proven to be rather difficult. METHODOLOGY/PRINCIPAL FINDINGS: Here we introduce the novel concept of ModuLand, an integrative method family determining overlapping network modules as hills of an influence function-based, centrality-type community landscape, and including several widely used modularization methods as special cases. As various adaptations of the method family, we developed several algorithms, which provide an efficient analysis of weighted and directed networks, and (1 determine persvasively overlapping modules with high resolution; (2 uncover a detailed hierarchical network structure allowing an efficient, zoom-in analysis of large networks; (3 allow the determination of key network nodes and (4 help to predict network dynamics. CONCLUSIONS/SIGNIFICANCE: The concept opens a wide range of possibilities to develop new approaches and applications including network routing, classification, comparison and prediction.

Localized modulated wave solutions in diffusive glucose–insulin systems

Energy Technology Data Exchange (ETDEWEB)

Mvogo, Alain, E-mail: mvogal_2009@yahoo.fr [Laboratory of Biophysics, Department of Physics, Faculty of Science, University of Yaounde I, P.O. Box 812, University of Yaounde (Cameroon); Centre d' Excellence Africain en Technologies de l' Information et de la Communication, University of Yaounde I (Cameroon); Tambue, Antoine [The African Institute for Mathematical Sciences (AIMS) and Stellenbosch University, 6-8 Melrose Road, Muizenberg 7945 (South Africa); Center for Research in Computational and Applied Mechanics (CERECAM), and Department of Mathematics and Applied Mathematics, University of Cape Town, 7701 Rondebosch (South Africa); Ben-Bolie, Germain H. [Centre d' Excellence Africain en Technologies de l' Information et de la Communication, University of Yaounde I (Cameroon); Laboratory of Nuclear Physics, Department of Physics, Faculty of Science, University of Yaounde I, P.O. Box 812, University of Yaounde (Cameroon); Kofané, Timoléon C. [Centre d' Excellence Africain en Technologies de l' Information et de la Communication, University of Yaounde I (Cameroon); Laboratory of Mechanics, Department of Physics, Faculty of Science, University of Yaounde I, P.O. Box 812, University of Yaounde (Cameroon)

2016-06-03

We investigate intercellular insulin dynamics in an array of diffusively coupled pancreatic islet β-cells. The cells are connected via gap junction coupling, where nearest neighbor interactions are included. Through the multiple scale expansion in the semi-discrete approximation, we show that the insulin dynamics can be governed by the complex Ginzburg–Landau equation. The localized solutions of this equation are reported. The results suggest from the biophysical point of view that the insulin propagates in pancreatic islet β-cells using both temporal and spatial dimensions in the form of localized modulated waves. - Highlights: • The dynamics of an array of diffusively coupled pancreatic islet beta-cells is investigated. • Through the multiple scale expansion, we show that the insulin dynamics can be governed by the complex Ginzburg–Landau equation. • Localized modulated waves are obtained for the insulin dynamics.

Substrate adhesion regulates sealing zone architecture and dynamics in cultured osteoclasts.

Directory of Open Access Journals (Sweden)

Fabian Anderegg

Full Text Available The bone-degrading activity of osteoclasts depends on the formation of a cytoskeletal-adhesive super-structure known as the sealing zone (SZ. The SZ is a dynamic structure, consisting of a condensed array of podosomes, the elementary adhesion-mediating structures of osteoclasts, interconnected by F-actin filaments. The molecular composition and structure of the SZ were extensively investigated, yet despite its major importance for bone formation and remodelling, the mechanisms underlying its assembly and dynamics are still poorly understood. Here we determine the relations between matrix adhesiveness and the formation, stability and expansion of the SZ. By growing differentiated osteoclasts on micro-patterned glass substrates, where adhesive areas are separated by non-adhesive PLL-g-PEG barriers, we show that SZ growth and fusion strictly depend on the continuity of substrate adhesiveness, at the micrometer scale. We present a possible model for the role of mechanical forces in SZ formation and reorganization, inspired by the current data.

Zero Cross-Talk Regimes in Dually Modulated Mutually-Coupled Nano-lasers

International Nuclear Information System (INIS)

Han, H; Zhang, M J; Wang, Y C; Shore, K A

2017-01-01

The modulation properties of dually modulated mutually-coupled nano-lasers have been analyzed using rate equations which include the Purcell cavity-enhanced spontaneous emission factor F and the spontaneous emission coupling factor β . Analysis of the dynamical response of modulated mutually-coupled nano-lasers reveals the existence of regimes of zero cross-talk wherein the response of one nano-laser is not impacted by the dynamics of the other nano-laser. The availability of zero-cross talk regimes is seen to offer opportunities for exploitation in photonic integrated circuits. (paper)

Bacterial subversion of host actin dynamics at the plasma membrane.

Science.gov (United States)

Carabeo, Rey

2011-10-01

Invasion of non-phagocytic cells by a number of bacterial pathogens involves the subversion of the actin cytoskeletal remodelling machinery to produce actin-rich cell surface projections designed to engulf the bacteria. The signalling that occurs to induce these actin-rich structures has considerable overlap among a diverse group of bacteria. The molecular organization within these structures act in concert to internalize the invading pathogen. This dynamic process could be subdivided into three acts - actin recruitment, engulfment, and finally, actin disassembly/internalization. This review will present the current state of knowledge of the molecular processes involved in each stage of bacterial invasion, and provide a perspective that highlights the temporal and spatial control of actin remodelling that occurs during bacterial invasion. © 2011 Blackwell Publishing Ltd.

Dynamical patterning modules: physico-genetic determinants of morphological development and evolution

International Nuclear Information System (INIS)

Newman, Stuart A; Bhat, Ramray

2008-01-01

The shapes and forms of multicellular organisms arise by the generation of new cell states and types and changes in the numbers and rearrangements of the various kinds of cells. While morphogenesis and pattern formation in all animal species are widely recognized to be mediated by the gene products of an evolutionarily conserved 'developmental-genetic toolkit', the link between these molecular players and the physics underlying these processes has been generally ignored. This paper introduces the concept of 'dynamical patterning modules' (DPMs), units consisting of one or more products of the 'toolkit' genes that mobilize physical processes characteristic of chemically and mechanically excitable meso- to macroscopic systems such as cell aggregates: cohesion, viscoelasticity, diffusion, spatiotemporal heterogeneity based on lateral inhibition and multistable and oscillatory dynamics. We suggest that ancient toolkit gene products, most predating the emergence of multicellularity, assumed novel morphogenetic functions due to change in the scale and context inherent to multicellularity. We show that DPMs, acting individually and in concert with each other, constitute a 'pattern language' capable of generating all metazoan body plans and organ forms. The physical dimension of developmental causation implies that multicellular forms during the explosive radiation of animal body plans in the middle Cambrian, approximately 530 million years ago, could have explored an extensive morphospace without concomitant genotypic change or selection for adaptation. The morphologically plastic body plans and organ forms generated by DPMs, and their ontogenetic trajectories, would subsequently have been stabilized and consolidated by natural selection and genetic drift. This perspective also solves the apparent 'molecular homology-analogy paradox', whereby widely divergent modern animal types utilize the same molecular toolkit during development by proposing, in contrast to the Neo

Intensity-modulated radiation therapy: dynamic MLC (DMLC) therapy, multisegment therapy and tomotherapy. An example of QA in DMLC therapy

International Nuclear Information System (INIS)

Webb, S.

1998-01-01

Intensity-modulated radiation therapy will make a quantum leap in tumor control. It is the new radiation therapy for the new millennium. The major methods to achieve IMRT are: 1. Dynamic multileaf collimator (DMLC) therapy, 2. multisegment therapy, and 3. tomotherapy. The principles of these 3 techniques are briefly reviewed. Each technique presents unique QA issues which are outlined. As an example this paper will present the results of a recent new study of an important QA concern in DMLC therapy. (orig.) [de

Divergent regulation of the sarcomere and the cytoskeleton.

Science.gov (United States)

Schevzov, Galina; Fath, Thomas; Vrhovski, Bernadette; Vlahovich, Nicole; Rajan, Sudarsan; Hook, Jeff; Joya, Josephine E; Lemckert, Frances; Puttur, Franz; Lin, Jim J-C; Hardeman, Edna C; Wieczorek, David F; O'Neill, Geraldine M; Gunning, Peter W

2008-01-04

The existence of a feedback mechanism regulating the precise amounts of muscle structural proteins, such as actin and the actin-associated protein tropomyosin (Tm), in the sarcomeres of striated muscles is well established. However, the regulation of nonmuscle or cytoskeletal actin and Tms in nonmuscle cell structures has not been elucidated. Unlike the thin filaments of striated muscles, the actin cytoskeleton in nonmuscle cells is intrinsically dynamic. Given the differing requirements for the structural integrity of the actin thin filaments of the sarcomere compared with the requirement for dynamicity of the actin cytoskeleton in nonmuscle cells, we postulated that different regulatory mechanisms govern the expression of sarcomeric versus cytoskeletal Tms, as key regulators of the properties of the actin cytoskeleton. Comprehensive analyses of tissues from transgenic and knock-out mouse lines that overexpress the cytoskeletal Tms, Tm3 and Tm5NM1, and a comparison with sarcomeric Tms provide evidence for this. Moreover, we show that overexpression of a cytoskeletal Tm drives the amount of filamentous actin.

Melanophores for microtubule dynamics and motility assays.

Science.gov (United States)

Ikeda, Kazuho; Semenova, Irina; Zhapparova, Olga; Rodionov, Vladimir

2010-01-01

Microtubules (MTs) are cytoskeletal structures essential for cell division, locomotion, intracellular transport, and spatial organization of the cytoplasm. In most interphase cells, MTs are organized into a polarized radial array with minus-ends clustered at the centrosome and plus-ends extended to the cell periphery. This array directs transport of organelles driven by MT-based motor proteins that specifically move either to plus- or to minus-ends. Along with using MTs as tracks for cargo, motor proteins can organize MTs into a radial array in the absence of the centrosome. Transport of organelles and motor-dependent radial organization of MTs require MT dynamics, continuous addition and loss of tubulin subunits at minus- and plus-ends. A unique experimental system for studying the role of MT dynamics in these processes is the melanophore, which provides a useful tool for imaging of both dynamic MTs and moving membrane organelles. Melanophores are filled with pigment granules that are synchronously transported by motor proteins in response to hormonal stimuli. The flat shape of the cell and the radial organization of MTs facilitate imaging of dynamic MT plus-ends and monitoring of their interaction with membrane organelles. Microsurgically produced cytoplasmic fragments of melanophores are used to study the centrosome-independent rearrangement of MTs into a radial array. Here we describe the experimental approaches to study the role of MT dynamics in intracellular transport and centrosome-independent MT organization in melanophores. We focus on the preparation of cell cultures, microsurgery and microinjection, fluorescence labeling, and live imaging of MTs. 2010 Elsevier Inc. All rights reserved.

Curcumin modulates endothelial permeability and monocyte transendothelial migration by affecting endothelial cell dynamics.

Science.gov (United States)

Monfoulet, Laurent-Emmanuel; Mercier, Sylvie; Bayle, Dominique; Tamaian, Radu; Barber-Chamoux, Nicolas; Morand, Christine; Milenkovic, Dragan

2017-11-01

Curcumin is a phenolic compound that exhibits beneficial properties for cardiometabolic health. We previously showed that curcumin reduced the infiltration of immune cells into the vascular wall and prevented atherosclerosis development in mice. This study aimed to investigate the effect of curcumin on monocyte adhesion and transendothelial migration (TEM) and to decipher the underlying mechanisms of these actions. Human umbilical vein endothelial cells (HUVECs) were exposed to curcumin (0.5-1μM) for 3h prior to their activation by Tumor Necrosis Factor alpha (TNF-α). Endothelial permeability, monocyte adhesion and transendothelial migration assays were conducted under static condition and shear stress that mimics blood flow. We further investigated the impact of curcumin on signaling pathways and on the expression of genes using macroarrays. Pre-exposure of endothelial cells to curcumin reduced monocyte adhesion and their transendothelial migration in both static and shear stress conditions. Curcumin also prevented changes in both endothelial permeability and the area of HUVECs when induced by TNF-α. We showed that curcumin modulated the expression of 15 genes involved in the control of cytoskeleton and endothelial junction dynamic. Finally, we showed that curcumin inhibited NF-κB signaling likely through an antagonist interplay with several kinases as suggested by molecular docking analysis. Our findings demonstrate the ability of curcumin to reduce monocyte TEM through a multimodal regulation of the endothelial cell dynamics with a potential benefit on the vascular endothelial function barrier. Copyright © 2017 Elsevier Inc. All rights reserved.

The Robust Control Mixer Module Method for Control Reconfiguration

DEFF Research Database (Denmark)

Yang, Z.; Blanke, M.

1999-01-01

into a LTI dynamical system, and furthermore multiple dynamical control mixer modules can be employed in our consideration. The H_{\\infty} control theory is used for the analysis and design of the robust control mixer modules. Finally, one practical robot arm system as benchmark is used to test the proposed......The control mixer concept is efficient in improving an ordinary control system into a fault tolerant one, especially for these control systems of which the real-time and on-line redesign of the control laws is very difficult. In order to consider the stability, performance and robustness...... of the reconfigurated system simultaneously, and to deal with a more general controller reconfiguration than the static feedback mechanism by using the control mixer approach, the robust control mixer module method is proposed in this paper. The form of the control mixer module extends from a static gain matrix...

SU-G-JeP4-13: Continuous Intra-Fractional Monitoring of the Prostate Using Dynamic KV Collimation and Tube Current Modulation

Energy Technology Data Exchange (ETDEWEB)

Parsons, D [Dalhousie Unviersity, Halifax, Nova Scotia (Canada); Robar, J [Dalhousie Unviersity, Halifax, Nova Scotia (Canada); Nova Scotia Health Authority, Halifax, NS (Canada)

2016-06-15

Purpose: The focus of this work is to improve the available kV image quality for continuous intra-fraction monitoring of the prostate. This is investigated using a novel blade collimation system enabling modulated volume-of-interest (VOI) imaging of prostate fiducial markers. Methods: A four-blade dynamic kV collimator was used to track a VOI during gantry rotation. Planar image quality was investigated as a function of collimator dimension, while maintaining the same dose to isocenter, for a 22.2 cm diameter cylindrical water phantom with a 9 mm diameter bone insert. A sample prostate anatomy was defined in the planning system, including three fiducial markers within the CTV. The VOI margin around each marker was set to be 2σ of the population covariance matrix characterizing prostate motion. DRRs were used to calculate the kV attenuation for each VOI as a function of angle. The optimal marker and tube current were determined using kV attenuation. Monte Carlo simulations were used to calculate the imaging dose to the phantom and MV scatter dose to the imaging panel. Results: Preliminary measurements show an increase in CNR by a factor of 1.3 with the VOI method, when decreasing from an 6×6 to 2×2 cm{sup 2} field. Attenuation calculations show a change in kV fluence at the detector by a factor of 21.6 with fiducial optimization; resultant tube current modulation increases maximum dose by a factor of 1.4 compared to no modulation. MV scatter contribution to the kV detector changes by approximately a factor of two over a complete gantry rotation. Conclusion: The dynamic collimation system allows single fiducial marker tracking at a very low dose, with reduction of scatter and improvement of image quality, compared to imaging the entire prostate. The approach is compatible with tube current modulation, which enables consistent image quality throughout the range of gantry rotation. This project was funded by Varian Medical Systems.

Convergent-beam electron diffraction study of incommensurately modulated crystals. Pt. 2. (3 + 1)-dimensional space groups

International Nuclear Information System (INIS)

Terauchi, Masami; Takahashi, Mariko; Tanaka, Michiyoshi

1994-01-01

The convergent-beam electron diffraction (CBED) method for determining three-dimensional space groups is extended to the determination of the (3 + 1)-dimensional space groups for one-dimensional incommensurately modulated crystals. It is clarified than an approximate dynamical extinction line appears in the CBED discs of the reflections caused by an incommensurate modulation. The extinction enables the space-group determination of the (3 + 1)-dimensional crystals or the one-dimensional incommensurately modulated crystals. An example of the dynamical extinction line is shown using an incommensurately modulated crystal of Sr 2 Nb 2 O 7 . Tables of the dynamical extinction lines appearing in CBED patterns are given for all the (3 + 1)-dimensional space groups of the incommensurately modulated crystal. (orig.)

High Affinity vs. Native Fibronectin in the Modulation of αvβ3 Integrin Conformational Dynamics: Insights from Computational Analyses and Implications for Molecular Design.

Directory of Open Access Journals (Sweden)

Antonella Paladino

2017-01-01

Full Text Available Understanding how binding events modulate functional motions of multidomain proteins is a major issue in chemical biology. We address several aspects of this problem by analyzing the differential dynamics of αvβ3 integrin bound to wild type (wtFN10, agonist or high affinity (hFN10, antagonist mutants of fibronectin. We compare the dynamics of complexes from large-scale domain motions to inter-residue coordinated fluctuations to characterize the distinctive traits of conformational evolution and shed light on the determinants of differential αvβ3 activation induced by different FN sequences. We propose an allosteric model for ligand-based integrin modulation: the conserved integrin binding pocket anchors the ligand, while different residues on the two FN10's act as the drivers that reorganize relevant interaction networks, guiding the shift towards inactive (hFN10-bound or active states (wtFN10-bound. We discuss the implications of results for the design of integrin inhibitors.

CONSERVED ROLES FOR CYTOSKELETAL COMPONENTS IN DETERMINING LATERALITY

Science.gov (United States)

McDowell, Gary S.; Lemire, Joan M.; Paré, Jean-Francois; Cammarata, Garrett; Lowery, Laura Anne; Levin, Michael

2016-01-01

SUMMARY Consistently-biased left-right (LR) patterning is required for the proper placement of organs including the heart and viscera. The LR axis is especially fascinating as an example of multi-scale pattern formation, since here chiral events at the subcellular level are integrated and amplified into asymmetric transcriptional cascades and ultimately into the anatomical patterning of the entire body. In contrast to the other two body axes, there is considerable controversy about the earliest mechanisms of embryonic laterality. Many molecular components of asymmetry have not been widely tested among phyla with diverse bodyplans, and it is unknown whether parallel (redundant) pathways may exist that could reverse abnormal asymmetry states at specific checkpoints in development. To address conservation of the early steps of LR patterning, we used the Xenopus laevis (frog) embryo to functionally test a number of protein targets known to direct asymmetry in plants, fruit fly, and rodent. Using the same reagents that randomize asymmetry in Arabidopsis, Drosophila, and mouse embryos, we show that manipulation of the microtubule and actin cytoskeleton immediately post-fertilization, but not later, results in laterality defects in Xenopus embryos. Moreover, we observed organ-specific randomization effects and a striking dissociation of organ situs from effects on the expression of left side control genes, which parallel data from Drosophila and mouse. Remarkably, some early manipulations that disrupt laterality of transcriptional asymmetry determinants can be subsequently “rescued” by the embryo, resulting in normal organ situs. These data reveal the existence of novel corrective mechanisms, demonstrate that asymmetric expression of Nodal is not a definitive marker of laterality, and suggest the existence of amplification pathways that connect early cytoskeletal processes to control of organ situs bypassing Nodal. Counter to alternative models of symmetry breaking

Using white noise to gate organic transistors for dynamic monitoring of cultured cell layers.

Science.gov (United States)

Rivnay, Jonathan; Leleux, Pierre; Hama, Adel; Ramuz, Marc; Huerta, Miriam; Malliaras, George G; Owens, Roisin M

2015-06-26

Impedance sensing of biological systems allows for monitoring of cell and tissue properties, including cell-substrate attachment, layer confluence, and the "tightness" of an epithelial tissue. These properties are critical for electrical detection of tissue health and viability in applications such as toxicological screening. Organic transistors based on conducting polymers offer a promising route to efficiently transduce ionic currents to attain high quality impedance spectra, but collection of complete impedance spectra can be time consuming (minutes). By applying uniform white noise at the gate of an organic electrochemical transistor (OECT), and measuring the resulting current noise, we are able to dynamically monitor the impedance and thus integrity of cultured epithelial monolayers. We show that noise sourcing can be used to track rapid monolayer disruption due to compounds which interfere with dynamic polymerization events crucial for maintaining cytoskeletal integrity, and to resolve sub-second alterations to the monolayer integrity.

Module responses in a tropical forest tree analyzed with a matrix model

NARCIS (Netherlands)

Sterck, F.J.; Bongers, F.J.J.M.; During, H.J.; Martinez-Ramos, M.; Kroon, de H.

2003-01-01

Module dynamics were studied for the shade-tolerant canopy tree species Vouacapoua americana in a French Guiana rain forest. A module life cycle graph was constructed, including all the possible transitions between four module states: apically growing (G), apically dormant (D), apically arrested

Variable-angle epifluorescence microscopy characterizes protein dynamics in the vicinity of plasma membrane in plant cells.

Science.gov (United States)

Chen, Tong; Ji, Dongchao; Tian, Shiping

2018-03-14

The assembly of protein complexes and compositional lipid patterning act together to endow cells with the plasticity required to maintain compositional heterogeneity with respect to individual proteins. Hence, the applications for imaging protein localization and dynamics require high accuracy, particularly at high spatio-temporal level. We provided experimental data for the applications of Variable-Angle Epifluorescence Microscopy (VAEM) in dissecting protein dynamics in plant cells. The VAEM-based co-localization analysis took penetration depth and incident angle into consideration. Besides direct overlap of dual-color fluorescence signals, the co-localization analysis was carried out quantitatively in combination with the methodology for calculating puncta distance and protein proximity index. Besides, simultaneous VAEM tracking of cytoskeletal dynamics provided more insights into coordinated responses of actin filaments and microtubules. Moreover, lateral motility of membrane proteins was analyzed by calculating diffusion coefficients and kymograph analysis, which represented an alternative method for examining protein motility. The present study presented experimental evidence on illustrating the use of VAEM in tracking and dissecting protein dynamics, dissecting endosomal dynamics, cell structure assembly along with membrane microdomain and protein motility in intact plant cells.

Role of internal demagnetizing field for the dynamics of a surface-modulated magnonic crystal

Science.gov (United States)

Langer, M.; Röder, F.; Gallardo, R. A.; Schneider, T.; Stienen, S.; Gatel, C.; Hübner, R.; Bischoff, L.; Lenz, K.; Lindner, J.; Landeros, P.; Fassbender, J.

2017-05-01

This work aims to demonstrate and understand the key role of local demagnetizing fields in hybrid structures consisting of a continuous thin film with a stripe modulation on top. To understand the complex spin dynamics of these structures, the magnonic crystal was reconstructed in two different ways—performing micromagnetic simulations based on the structural shape as well as based on the internal demagnetizing field, which both are mapped on the nanoscale using electron holography. The simulations yield the frequency-field dependence as well as the angular dependence revealing the governing role of the internal field landscape around the backward-volume geometry. Simple rules for the propagation vector and the mode localization are formulated in order to explain the calculated mode profiles. Treating internal demagnetizing fields equivalent to anisotropies, the complex angle-dependent spin-wave behavior is described for an in-plane rotation of the external field.

Controlling traffic jams by time modulating the safety distance

DEFF Research Database (Denmark)

Gaididei, Yu B.; Gorria, C.; Berkemer, R.

2013-01-01

The possibility of controlling traffic dynamics by applying high-frequency time modulation of traffic flow parameters is studied. It is shown that the region of the car density where the uniform (free) flow is unstable changes in the presence of time modulation compared with the unmodulated case....

Gas flow characteristics of a time modulated APPJ: the effect of gas heating on flow dynamics

International Nuclear Information System (INIS)

Zhang, S; Sobota, A; Van Veldhuizen, E M; Bruggeman, P J

2015-01-01

This work investigates the flow dynamics of a radio-frequency (RF) non-equilibrium argon atmospheric pressure plasma jet. The RF power is at a frequency of 50 Hz or 20 kHz. Combined flow pattern visualizations (obtained by shadowgraphy) and gas temperature distributions (obtained by Rayleigh scattering) are used to study the formation of transient vortex structures in initial flow field shortly after the plasma is switched on and off in the case of 50 Hz modulation. The transient vortex structures correlate well with observed temperature differences. Experimental results of the fast modulated (20 kHz) plasma jet that does not induce changes of the gas temperature are also presented. The latter result suggests that momentum transfer by ions does not have dominant effect on the flow pattern close to the tube. It is argued that the increased gas temperature and corresponding gas velocity increase at the tube exit due to the plasma heating increases the admixing of surrounding air and reduces the effective potential core length. With increasing plasma power a reduction of the effective potential core length is observed with a minimum length for 5.6 W after which the length extends again. Possible mechanisms related to viscosity effects and ionic momentum transfer are discussed. (paper)

Modulation of expression of genes encoding nuclear proteins following exposure to JANUS neutrons or γ-rays

International Nuclear Information System (INIS)

Woloschak, G.E.; Chang-Liu, Chin-Mei

1994-01-01

Previous work has shown that exposure of cells to ionizing radiations causes modulation of a variety of genes, including those encoding c-fos, interleukin-1, tumor necrosis factor, cytoskeletal elements, and many more. The experiments reported herein were designed to examine the effects of either JANUS neutron or γ-ray exposure on expression of genes encoding nucleus-associated proteins (H4-histone, c-jun, c-myc, Rb, and p53). Cycling Syrian hamster embryo cells were irradiated with varying doses and dose rates of either JANUS fission-spectrum neutrons or γ-rays; after incubation of the cell cultures for 1 h following radiation exposure, mRNA was harvested and analyzed by Northern blot. Results revealed induction of transcripts for c-jun, H4-histone, and Rb following γ-ray but not following neutron exposure. Interestingly, expression of c-myc was repressed following γ-ray but not following neutron exposure. Radiations at different doses and dose rates were compared for each of the genes studied

Sigma-delta modulator modeling analysis and design

International Nuclear Information System (INIS)

Ge Binjie; Wang Xin'an; Zhang Xing; Feng Xiaoxing; Wang Qingqin

2010-01-01

This paper introduces a new method for SC sigma-delta modulator modeling. It studies the integrator's different equivalent circuits in the integrating and sampling phases. This model uses the OP-AMP input pair's tail current (I 0 ) and overdrive voltage (v on ) as variables. The modulator's static and dynamic errors are analyzed. A group of optimized I 0 and v on for maximum SNR and power x area ratio can be obtained through this model. As examples, a MASH21 modulator for digital audio and a second order modulator for RFID baseband are implemented and tested, and they can achieve 91 dB and 72 dB respectively, which verifies the modeling and design criteria. (semiconductor integrated circuits)

Intensity-modulated three-dimensional conformal radiotherapy

International Nuclear Information System (INIS)

Mohan, Radhe

1996-01-01

Optimized intensity-modulated treatments one of the important advances in photon radiotherapy. Intensity modulation provides a greatly increased control over dose distributions. Such control can be maximally exploited to achieve significantly higher levels of conformation to the desired clinical objectives using sophisticated optimization techniques. Safe, rapid and efficient delivery of intensity-modulated treatments has become feasible using a dynamic multi-leaf collimator under computer control. The need for all other field shaping devices such as blocks, wedges and compensators is eliminated. Planning and delivery of intensity-modulated treatments is amenable to automation and development of class solutions for each treatment site and stage which can be implemented not only at major academic centers but on a wide scale. A typical treatment involving as many as 10 fields can be delivered in times shorter than much simpler conventional treatments. The main objective of the course is to give an overview of the current state of the art of planning and delivery methods of intensity-modulated treatments. Specifically, the following topics will be covered using representative optimized plans and treatments: 1. A typical procedure for planning and delivering an intensity-modulated treatment. 2. Quantitative definition of criteria (i.e., the objective function) of optimization of intensity-modulated treatments. Clinical relevance of objectives and the dependence of the quality of optimized intensity-modulated plans upon whether the objectives are stated purely in terms of simple dose or dose-volume criteria or whether they incorporate biological indices. 3. Importance of the lateral transport of radiation in the design of intensity-modulated treatments. Impact on dose homogeneity and the optimum choice of margins. 4. Use of intensity-modulated treatments in escalation of tumor dose for the same or lower normal tissue dose. Fractionation of intensity-modulated treatments

Intensity-modulated three-dimensional conformal radiotherapy

International Nuclear Information System (INIS)

Mohan, Radhe

1997-01-01

Optimized intensity-modulated treatments one of the important advances in photon radiotherapy. Intensity modulation provides a greatly increased control over dose distributions. Such control can be maximally exploited to achieve significantly higher levels of conformation to the desired clinical objectives using sophisticated optimization techniques. Safe, rapid and efficient delivery of intensity-modulated treatments has become feasible using a dynamic multi-leaf collimator under computer control. The need for all other field shaping devices such as blocks, wedges and compensators is eliminated. Planning and delivery of intensity-modulated treatments is amenable to automation and development of class solutions for each treatment site and stage which can be implemented not only at major academic centers but on a wide scale. A typical treatment involving as many as 10 fields can be delivered in times shorter than much simpler conventional treatments. The main objective of the course is to give an overview of the current state of the art of planning and delivery methods of intensity-modulated treatments. Specifically, the following topics will be covered using representative optimized plans and treatments: 1. A typical procedure for planning and delivering an intensity-modulated treatment. 2. Quantitative definition of criteria (i.e., the objective function) of optimization of intensity-modulated treatments. Clinical relevance of objectives and the dependence of the quality of optimized intensity-modulated plans upon whether the objectives are stated purely in terms of simple dose or dose-volume criteria or whether they incorporate biological indices. 3. Importance of the lateral transport of radiation in the design of intensity-modulated treatments. Impact on dose homogeneity and the optimum choice of margins. 4. Use of intensity-modulated treatments in escalation of tumor dose for the same or lower normal tissue dose. Fractionation of intensity-modulated treatments

A composite role of vitronectin and urokinase in the modulation of cell morphology upon expression of the urokinase receptor

DEFF Research Database (Denmark)

Engelholm, L.H.; Ingvarsen, S.; Madsen, D.H.

2008-01-01

, and this event is followed by downstream effects including changes in the cytoskeletal organization. However, it remains unclear whether the adhesion through uPAR-vitronectin is the only event capable of initiating these morphological rearrangements or whether lateral interactions between uPAR and integrins can...... adhesion and cytoskeletal rearrangements, whereas a mutant uPAR, uPAR(W32A) with defective vitronectin binding, failed to induce both phenomena. However, upon saturation of uPAR(W32A) with the protease ligand, pro-uPA, or its receptor-binding domain, the ability to induce cytoskeletal rearrangements...... was restored, although this did not rescue the uPAR-vitronectin binding and adhesion capability. On the other hand, using other uPAR variants, we could show that uPAR-vitronectin adhesion is indeed capable and sufficient to induce the same morphological rearrangements. This was shown with cells expressing...

Phase matching of high order harmonic generation using dynamic phase modulation caused by a non-collinear modulation pulse

Science.gov (United States)

Cohen, Oren; Kapteyn, Henry C.; Mumane, Margaret M.

2010-02-16

Phase matching high harmonic generation (HHG) uses a single, long duration non-collinear modulating pulse intersecting the driving pulse. A femtosecond driving pulse is focused into an HHG medium (such as a noble gas) to cause high-harmonic generation (HHG), for example in the X-ray region of the spectrum, via electrons separating from and recombining with gas atoms. A non-collinear pulse intersects the driving pulse within the gas, and modulates the field seen by the electrons while separated from their atoms. The modulating pulse is low power and long duration, and its frequency and amplitude is chosen to improve HHG phase matching by increasing the areas of constructive interference between the driving pulse and the HHG, relative to the areas of destructive interference.

Electrothermal Frequency Modulated Resonator for Mechanical Memory

KAUST Repository

Hafiz, Md Abdullah Al; Kosuru, Lakshmoji; Younis, Mohammad I.

2016-01-01

In this paper, we experimentally demonstrate a mechanical memory device based on the nonlinear dynamics of an electrostatically actuated microelectromechanical resonator utilizing an electrothermal frequency modulation scheme. The microstructure

Density Structures, Dynamics, and Seasonal and Solar Cycle Modulations of Saturn's Inner Plasma Disk

Science.gov (United States)

Holmberg, M. K. G.; Shebanits, O.; Wahlund, J.-E.; Morooka, M. W.; Vigren, E.; André, N.; Garnier, P.; Persoon, A. M.; Génot, V.; Gilbert, L. K.

2017-12-01

We present statistical results from the Cassini Radio and Plasma Wave Science (RPWS) Langmuir probe measurements recorded during the time interval from orbit 3 (1 February 2005) to 237 (29 June 2016). A new and improved data analysis method to obtain ion density from the Cassini LP measurements is used to study the asymmetries and modulations found in the inner plasma disk of Saturn, between 2.5 and 12 Saturn radii (1 RS=60,268 km). The structure of Saturn's plasma disk is mapped, and the plasma density peak, nmax, is shown to be located at ˜4.6 RS and not at the main neutral source region at 3.95 RS. The shift in the location of nmax is due to that the hot electron impact ionization rate peaks at ˜4.6 RS. Cassini RPWS plasma disk measurements show a solar cycle modulation. However, estimates of the change in ion density due to varying EUV flux is not large enough to describe the detected dependency, which implies that an additional mechanism, still unknown, is also affecting the plasma density in the studied region. We also present a dayside/nightside ion density asymmetry, with nightside densities up to a factor of 2 larger than on the dayside. The largest density difference is found in the radial region 4 to 5 RS. The dynamic variation in ion density increases toward Saturn, indicating an internal origin of the large density variability in the plasma disk rather than being caused by an external source origin in the outer magnetosphere.

Imidazoles and benzimidazoles as tubulin-modulators for anti-cancer therapy.

Science.gov (United States)

Torres, Fernando C; García-Rubiño, M Eugenia; Lozano-López, César; Kawano, Daniel F; Eifler-Lima, Vera L; von Poser, Gilsane L; Campos, Joaquín M

2015-01-01

Imidazoles and benzimidazoles are privileged heterocyclic bioactive compounds used with success in the clinical practice of innumerous diseases. Although there are many advancements in cancer therapy, microtubules remain as one of the few macromolecular targets validated for planning active anti-cancer compounds, and the design of drugs that modulate microtubule dynamics in unknown sites of tubulin is one of the goals of the medicinal chemistry. The discussion of the role of new and commercially available imidazole and benzimidazole derivatives as tubulin modulators is scattered throughout scientific literature, and indicates that these compounds have a tubulin modulation mechanism different from that of tubulin modulators clinically available, such as paclitaxel, docetaxel, vincristine and vinblastine. In fact, recent literature indicates that these derivatives inhibit microtubule formation binding to the colchicine site, present good pharmacokinetic properties and are capable of overcoming multidrug resistance in many cell lines. The understanding of the mechanisms involved in the imidazoles/benzimidazoles modulation of microtubule dynamics is very important to develop new strategies to overcome the resistance to anti-cancer drugs and to discover new biomarkers and targets for cancer chemotherapy.

Dynamic Simulator for Nuclear Power Plants (DSNP)

International Nuclear Information System (INIS)

Saphier, D.

1976-01-01

A new simulation language DSNP (Dynamic Simulator for Nuclear Power Plants) is being developed. It is a simple block oriented simulation language with an extensive library of component and auxiliary modules. Each module is a self-contained unit of a part of a physical component to be found in nuclear power plants. Each module will be available in four levels of sophistication, the fourth being a user supplied model. A module can be included in the simulation by a single statement. The precompiler translates DSNP statements into FORTRAN statements, takes care of the module parameters and the intermodular communication blocks, prepares proper data files and I/0 statements and searches the various libraries for the appropriate component modules. The documentation is computerized and all the necessary information for a particular module can be retrieved by a special document generator. The DSNP will be a flexible tool which will allow dynamic simulations to be performed on a large variety of nuclear power plants or specific components of these plants

Large enhancement of deuteron polarization with frequency modulated microwaves

CERN Document Server

AUTHOR|(CDS)2067425; Arik, S; Arvidson, A; Badelek, B; Ballintijn, M K; Bardin,; Baum, G; Berglund, P; Betev, L; Birda, I G; Birsa, R; Bjrkholm, P; Bonner, B E; de Botton, N; Boutemeur, M; Bradamante, Franco; Bressan, A; Brullc, A; Buchanan, J; Bültmann, S; Burtin, E; Cavata, C; Chen, J P; Clement, J; Clocchiatti, M; Corcoran, M D; Crabb, D; Cranshaw, J; Çuhadar-Dönszelmann, T; Deshpande, S; Dalla Torre, A; Van Dantzig, R; Dhawan, S; Dulya, C; Dyring, A; Eichblatt, S; Faivre, Jean-Claude; Fasching, D; Day, D; Feinstein, F; Fernández, C; Frois, B; Garabatos, C; Garzón, J A; Gaussiran, T; Giorgi, M; von Goeler, E; Goloutvin, Igor A; Gómez, A; Gracia, G; De Groot, N; Grosse-Perdekamp, M; Gülmez, E; Hasegawa, T; Hautle, P; Hayashi, N; Heusch, C A; Horikawa, D; von Harrach, N; Hughes, V W; Igo, G; Ishimoto, S; Iwata, T; De Jong, M; Kabu, E M; Kageya, T; Kaiser, R; Karev, A; Kessler, H J; Ketel, T J; Kiryushin, Yu T; Kishi, A; Kisselev, Yu; Klostermann, L; Krämer, Dietrich; Kukhtin, V; Kyynarinen, J; Lamanna, M; Landgraf, U; Lau, V; Krivokhijinea, K; Layda, T; Le Go, J M; Lehár, F; de Lesquen, A; Lichtenstadt, J; Lindqvist, T; Litmaath, M; López-Ponte, S; Loewe, M; Magnon, A; Mallot, G K; Marie, F; Martin, A; Martino, J; Matsuda, T; Mayes, B; McCarthy, J S; van Middelkoop, K; Medved, G; Miller, D; Mitchell, J; Mori, K; Moromisato, J; Mutchler, G S; Nagaitsev, A; Nassalski, J; Naumann, Lutz; Neganov, B; Niinikoski, T O; Oberski, J E J; Ogawa, A; Okumi, S; Ozben, C S; Penzo, Aldo L; Pérez, C A; Perrot-Kunne, F; Piegaia, R; Pinsky, L; Platchkov, S; Pló, M; Pose, D; Postma, D; Peshekhonov, H; Pretz, J; Pussieux, T; Pyrlik, J; Reyhancan, I; Rieubland, Jean Michel; Rijllart, A; Roberts, J B; Rock, S E; Rodríguez, M; Rondio, E; Rondon, O; Ropelewski, Leszek; Rosado, A; Sabo, I; Saborido, J; Salvato, G; Sandacz, A; Sanders, D; Savin, I; Schiavon, Paolo; Schüler, K P; Segel, R; Seitz, R; Semertzidis, Y; Sergeev, S; Sever, F; Shanahan, P; Sichtermann, E P; Smirnov, G; Staude, A; Steinmetz, A; Stuhrmann, H; Teichert, K M; Tessarotto, F; Thiel, W; Velasco, M; Vogt, J; Voss, R; Weinstein, R; Whitten, C; Willumeit, R; Windmolders, R; Wislicki, W; Witzmann, A; Yañez, A; Zanetti, A M; Zhao, J; Zamiatin, N I

1996-01-01

We report a large enhancement of 1.7 in deuteron polarization up to values of 0.6 due to frequency modulation of the polarizing microwaves in a two liters polarized target using the method of dynamic nuclear polarization. This target was used during a deep inelastic polarized muon-deuteron scattering experiment at CERN. Measurements of the electron paramagnetic resonance absorption spectra show that frequency modulation gives rise to additional microwave absorption in the spectral wings. Although these results are not understood theoretically, they may provide a useful testing ground for the deeper understanding of dynamic nuclear polarization.

Energetic changes caused by antigenic module insertion in a virus-like particle revealed by experiment and molecular dynamics simulations.

Directory of Open Access Journals (Sweden)

Lin Zhang

Full Text Available The success of recombinant virus-like particles (VLPs for human papillomavirus and hepatitis B demonstrates the potential of VLPs as safe and efficacious vaccines. With new modular designs emerging, the effects of antigen module insertion on the self-assembly and structural integrity of VLPs should be clarified so as to better enabling improved design. Previous work has revealed insights into the molecular energetics of a VLP subunit, capsomere, comparing energetics within various solution conditions known to drive or inhibit self-assembly. In the present study, molecular dynamics (MD simulations coupled with the molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA method were performed to examine the molecular interactions and energetics in a modular capsomere of a murine polyomavirus (MPV VLP designed to protect against influenza. Insertion of an influenza antigenic module is found to lower the binding energy within the capsomere, and a more active state is observed in Assembly Buffer as compared with that in Stabilization Buffer, which has been experimentally validated through measurements using differential scanning calorimetry. Further in-depth analysis based on free-energy decomposition indicates that destabilized binding can be attributed to electrostatic interaction induced by the chosen antigen module. These results provide molecular insights into the conformational stability of capsomeres and their abilities to be exploited for antigen presentation, and are expected to be beneficial for the biomolecular engineering of VLP vaccines.

Ring resonator-based on-chip modulation transformer for high-performance phase-modulated microwave photonic links.

Science.gov (United States)

Zhuang, Leimeng; Taddei, Caterina; Hoekman, Marcel; Leinse, Arne; Heideman, René; van Dijk, Paulus; Roeloffzen, Chris

2013-11-04

In this paper, we propose and experimentally demonstrate a novel wideband on-chip photonic modulation transformer for phase-modulated microwave photonic links. The proposed device is able to transform phase-modulated optical signals into intensity-modulated versions (or vice versa) with nearly zero conversion of laser phase noise to intensity noise. It is constructed using waveguide-based ring resonators, which features simple architecture, stable operation, and easy reconfigurability. Beyond the stand-alone functionality, the proposed device can also be integrated with other functional building blocks of photonic integrated circuits (PICs) to create on-chip complex microwave photonic signal processors. As an application example, a PIC consisting of two such modulation transformers and a notch filter has been designed and realized in TriPleX(TM) waveguide technology. The realized device uses a 2 × 2 splitting circuit and 3 ring resonators with a free spectral range of 25 GHz, which are all equipped with continuous tuning elements. The device can perform phase-to-intensity modulation transform and carrier suppression simultaneously, which enables high-performance phase-modulated microwave photonics links (PM-MPLs). Associated with the bias-free and low-complexity advantages of the phase modulators, a single-fiber-span PM-MPL with a RF bandwidth of 12 GHz (3 dB-suppression band 6 to 18 GHz) has been demonstrated comprising the proposed PIC, where the achieved spurious-free dynamic range performance is comparable to that of Class-AB MPLs using low-biased Mach-Zehnder modulators.

Physiological modules for generating discrete and rhythmic movements: action identification by a dynamic recurrent neural network.

Science.gov (United States)

Bengoetxea, Ana; Leurs, Françoise; Hoellinger, Thomas; Cebolla, Ana M; Dan, Bernard; McIntyre, Joseph; Cheron, Guy

2014-01-01

In this study we employed a dynamic recurrent neural network (DRNN) in a novel fashion to reveal characteristics of control modules underlying the generation of muscle activations when drawing figures with the outstretched arm. We asked healthy human subjects to perform four different figure-eight movements in each of two workspaces (frontal plane and sagittal plane). We then trained a DRNN to predict the movement of the wrist from information in the EMG signals from seven different muscles. We trained different instances of the same network on a single movement direction, on all four movement directions in a single movement plane, or on all eight possible movement patterns and looked at the ability of the DRNN to generalize and predict movements for trials that were not included in the training set. Within a single movement plane, a DRNN trained on one movement direction was not able to predict movements of the hand for trials in the other three directions, but a DRNN trained simultaneously on all four movement directions could generalize across movement directions within the same plane. Similarly, the DRNN was able to reproduce the kinematics of the hand for both movement planes, but only if it was trained on examples performed in each one. As we will discuss, these results indicate that there are important dynamical constraints on the mapping of EMG to hand movement that depend on both the time sequence of the movement and on the anatomical constraints of the musculoskeletal system. In a second step, we injected EMG signals constructed from different synergies derived by the PCA in order to identify the mechanical significance of each of these components. From these results, one can surmise that discrete-rhythmic movements may be constructed from three different fundamental modules, one regulating the co-activation of all muscles over the time span of the movement and two others elliciting patterns of reciprocal activation operating in orthogonal directions.

A Voltage Modulated DPC Approach for Three-Phase PWM Rectifier

DEFF Research Database (Denmark)

Gui, Yonghao; Li, Mingshen; Lu, Jinghang

2018-01-01

In this paper, a voltage modulated direct power control for three-phase pulse-width modulated rectifier is proposed. With the suggested method, the differential equations describing the rectifier dynamics are changing from a linear time-varying system into a linear time-invariant one. In this way...

Identification of mechanosensitive genes during skeletal development: alteration of genes associated with cytoskeletal rearrangement and cell signalling pathways.

Science.gov (United States)

Rolfe, Rebecca A; Nowlan, Niamh C; Kenny, Elaine M; Cormican, Paul; Morris, Derek W; Prendergast, Patrick J; Kelly, Daniel; Murphy, Paula

2014-01-20

Mechanical stimulation is necessary for regulating correct formation of the skeleton. Here we test the hypothesis that mechanical stimulation of the embryonic skeletal system impacts expression levels of genes implicated in developmentally important signalling pathways in a genome wide approach. We use a mutant mouse model with altered mechanical stimulation due to the absence of limb skeletal muscle (Splotch-delayed) where muscle-less embryos show specific defects in skeletal elements including delayed ossification, changes in the size and shape of cartilage rudiments and joint fusion. We used Microarray and RNA sequencing analysis tools to identify differentially expressed genes between muscle-less and control embryonic (TS23) humerus tissue. We found that 680 independent genes were down-regulated and 452 genes up-regulated in humeri from muscle-less Spd embryos compared to littermate controls (at least 2-fold; corrected p-value ≤0.05). We analysed the resulting differentially expressed gene sets using Gene Ontology annotations to identify significant enrichment of genes associated with particular biological processes, showing that removal of mechanical stimuli from muscle contractions affected genes associated with development and differentiation, cytoskeletal architecture and cell signalling. Among cell signalling pathways, the most strongly disturbed was Wnt signalling, with 34 genes including 19 pathway target genes affected. Spatial gene expression analysis showed that both a Wnt ligand encoding gene (Wnt4) and a pathway antagonist (Sfrp2) are up-regulated specifically in the developing joint line, while the expression of a Wnt target gene, Cd44, is no longer detectable in muscle-less embryos. The identification of 84 genes associated with the cytoskeleton that are down-regulated in the absence of muscle indicates a number of candidate genes that are both mechanoresponsive and potentially involved in mechanotransduction, converting a mechanical stimulus

The effects of near-UV radiation on elasmobranch lens cytoskeletal actin.

Science.gov (United States)

Zigman, S; Rafferty, N S; Scholz, D L; Lowe, K

1992-08-01

The role of near-UV radiation as a cytoskeletal actin-damaging agent was investigated. Two procedures were used to analyse fresh smooth dogfish (Mustelus canis) eye lenses that were incubated for up to 22 hr in vitro, with elasmobranch Ringer's medium, and with or without exposure to a near-UV lamp (emission principally at 365 nm; irradiance of 2.5 mW cm-2). These were observed histologically using phalloidin-rhodamine specific staining and by transmission electron microscopy. In addition, solutions of purified polymerized rabbit muscle actin were exposed to the same UV conditions and depolymerization was assayed by ultracentrifugation and high-pressure liquid chromatography. While the two actins studied do differ very slightly in some amino acid sequences, they would react physically nearly identically. The results showed that dogfish lenses developed superficial opacities due to near-UV exposure. Whole mounts of lens epithelium exhibited breakdown of actin filaments in the basal region of the cells within 18 hr of UV exposure. TEM confirmed the breakdown of actin filaments due to UV exposure. SDS-PAGE and immunoblotting positively identified actin in these cells. Direct exposure of purified polymerized muscle actin in polymerizing buffer led to an increase in actin monomer of approximately 25% in the UV-exposed solutions within 3-18 hr, whether assayed by ultracentrifugation or HPLC. The above indicates that elasmobranch lens epithelial cells contain UV-labile actin filaments, and that near-UV radiation, as is present in the sunlit environment, can break down the actin structure in these cells. Furthermore, breakdown of purified polymerized muscle actin does occur due to near-UV light exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Virtual Habitat -a dynamic simulation of closed life support systems -human model status

Science.gov (United States)

Markus Czupalla, M. Sc.; Zhukov, Anton; Hwang, Su-Au; Schnaitmann, Jonas

In order to optimize Life Support Systems on a system level, stability questions must be in-vestigated. To do so the exploration group of the Technical University of Munich (TUM) is developing the "Virtual Habitat" (V-HAB) dynamic LSS simulation software. V-HAB shall provide the possibility to conduct dynamic simulations of entire mission scenarios for any given LSS configuration. The Virtual Habitat simulation tool consists of four main modules: • Closed Environment Module (CEM) -monitoring of compounds in a closed environment • Crew Module (CM) -dynamic human simulation • P/C Systems Module (PCSM) -dynamic P/C subsystems • Plant Module (PM) -dynamic plant simulation The core module of the simulation is the dynamic and environment sensitive human module. Introduced in its basic version in 2008, the human module has been significantly updated since, increasing its capabilities and maturity significantly. In this paper three newly added human model subsystems (thermal regulation, digestion and schedule controller) are introduced touching also on the human stress subsystem which is cur-rently under development. Upon the introduction of these new subsystems, the integration of these into the overall V-HAB human model is discussed, highlighting the impact on the most important I/F. The overall human model capabilities shall further be summarized and presented based on meaningful test cases. In addition to the presentation of the results, the correlation strategy for the Virtual Habitat human model shall be introduced assessing the models current confidence level and giving an outlook on the future correlation strategy. Last but not least, the remaining V-HAB mod-ules shall be introduced shortly showing how the human model is integrated into the overall simulation.

Bismuth ferrite as low-loss switchable material for plasmonic waveguide modulator

DEFF Research Database (Denmark)

Babicheva, Viktoriia; Zhukovsky, Sergei; Lavrinenko, Andrei

2014-01-01

We propose new designs of plasmonic modulators, which can beused for dynamic signal switching in photonic integrated circuits. We studyperformance of a plasmonic waveguide modulator with bismuth ferrite as atunable material. The bismuth ferrite core is sandwiched between metalplates (metal...

Binaural processing of modulated interaural level differences

DEFF Research Database (Denmark)

Thompson, Eric Robert; Dau, Torsten

2008-01-01

Two experiments are presented that measure the acuity of binaural processing of modulated interaural level differences ILDs using psychoacoustic methods. In both experiments, dynamic ILDs were created by imposing an interaurally antiphasic sinusoidal amplitude modulation AM signal on high...... frequency, broadly tuned, bandpass-shaped patterns were obtained. Simulations with an existing binaural model show that a low-pass filter to limit the binaural temporal resolution is not sufficient to predict the results of the experiments....

Optimizing Energy and Modulation Selection in Multi-Resolution Modulation For Wireless Video Broadcast/Multicast

KAUST Repository

She, James

2009-11-01

Emerging technologies in Broadband Wireless Access (BWA) networks and video coding have enabled high-quality wireless video broadcast/multicast services in metropolitan areas. Joint source-channel coded wireless transmission, especially using hierarchical/superposition coded modulation at the channel, is recognized as an effective and scalable approach to increase the system scalability while tackling the multi-user channel diversity problem. The power allocation and modulation selection problem, however, is subject to a high computational complexity due to the nonlinear formulation and huge solution space. This paper introduces a dynamic programming framework with conditioned parsing, which significantly reduces the search space. The optimized result is further verified with experiments using real video content. The proposed approach effectively serves as a generalized and practical optimization framework that can gauge and optimize a scalable wireless video broadcast/multicast based on multi-resolution modulation in any BWA network.

Optimizing Energy and Modulation Selection in Multi-Resolution Modulation For Wireless Video Broadcast/Multicast

KAUST Repository

She, James; Ho, Pin-Han; Shihada, Basem

2009-01-01

Emerging technologies in Broadband Wireless Access (BWA) networks and video coding have enabled high-quality wireless video broadcast/multicast services in metropolitan areas. Joint source-channel coded wireless transmission, especially using hierarchical/superposition coded modulation at the channel, is recognized as an effective and scalable approach to increase the system scalability while tackling the multi-user channel diversity problem. The power allocation and modulation selection problem, however, is subject to a high computational complexity due to the nonlinear formulation and huge solution space. This paper introduces a dynamic programming framework with conditioned parsing, which significantly reduces the search space. The optimized result is further verified with experiments using real video content. The proposed approach effectively serves as a generalized and practical optimization framework that can gauge and optimize a scalable wireless video broadcast/multicast based on multi-resolution modulation in any BWA network.

Dosimetric comparison of volumetric modulated arc therapy (VMAT), DMlC (Dynamic IMRT), and 3DCRT in left breast cancer after breast conserving surgery receiving left breast irradiation

International Nuclear Information System (INIS)

Pratibha, Bauskar; Vibhay, Pareek; Rajendra, Bhalavat; Chandra, Manish

2016-01-01

Previous studies have demonstrated that the risk of ischemic heart disease is increased as a result of exposure to ionizing radiation in women treated for breast cancer. Alternative radiation techniques, such as dynamic intensity-modulated radiation therapy (DMLC), volumetric-modulated arc therapy (VMAT), have been shown to improve dosimetric parameters of the heart and substructures. However, these techniques have not been compared with each other to potentially guide treatment decisions. Volumetric modulated arc therapy (VMAT) is a novel extension of conventional intensity-modulated radiotherapy (c-IMRT), in which an optimized three dimensional dose distribution may be delivered in a single gantry rotation. VMAT is the predecessor to Rapid-Arc (Varian Medical System). This study uses VMAT, DMLC and 3DCRT to compare target volume coverage and doses to organs at risk (OARs), especially lung and heart doses, using these three techniques in whole breast irradiation after breast conserving surgery in left breast cancer cases

Arsenic trioxide (AT) is a novel human neutrophil pro-apoptotic agent: effects of catalase on AT-induced apoptosis, degradation of cytoskeletal proteins and de novo protein synthesis.

Science.gov (United States)

Binet, François; Cavalli, Hélène; Moisan, Eliane; Girard, Denis

2006-02-01

The anti-cancer drug arsenic trioxide (AT) induces apoptosis in a variety of transformed or proliferating cells. However, little is known regarding its ability to induce apoptosis in terminally differentiated cells, such as neutrophils. Because neutropenia has been reported in some cancer patients after AT treatment, we hypothesised that AT could induce neutrophil apoptosis, an issue that has never been investigated. Herein, we found that AT-induced neutrophil apoptosis and gelsolin degradation via caspases. AT did not increase neutrophil superoxide production and did not induce mitochondrial generation of reactive oxygen species. AT-induced apoptosis in PLB-985 and X-linked chronic granulomatous disease (CGD) cells (PLB-985 cells deficient in gp91(phox) mimicking CGD) at the same potency. Addition of catalase, an inhibitor of H2O2, reversed AT-induced apoptosis and degradation of the cytoskeletal proteins gelsolin, alpha-tubulin and lamin B1. Unexpectedly, AT-induced de novo protein synthesis, which was reversed by catalase. Cycloheximide partially reversed AT-induced apoptosis. We conclude that AT induces neutrophil apoptosis by a caspase-dependent mechanism and via de novo protein synthesis. H2O2 is of major importance in AT-induced neutrophil apoptosis but its production does not originate from nicotinamide adenine dinucleotide phosphate dehydrogenase activation and mitochondria. Cytoskeletal structures other than microtubules can now be considered as novel targets of AT.

A terahertz EO detector with large dynamical range, high modulation depth and signal-noise ratio

Science.gov (United States)

Pan, Xinjian; Cai, Yi; Zeng, Xuanke; Zheng, Shuiqin; Li, Jingzhen; Xu, Shixiang

2017-05-01

The paper presents a novel design for terahertz (THz) free-space time domain electro-optic (EO) detection where the static birefringent phases of the two balanced arms are set close to zero but opposite to each other. Our theoretical and numerical analyses show this design has much stronger ability to cancel the optical background noise than both THz ellipsometer and traditional crossed polarizer geometry (CPG). Its optical modulation depth is about twice as high as that of traditional CPG, but about ten times as high as that of THz ellipsometer. As for the dynamical range, our improved design is comparable to the THz ellipsometer but obviously larger than the traditional CPG. Some experiments for comparing our improved CPG with traditional CPG agree well with the corresponding theoretical predictions. Our experiments also show that the splitting ratio of the used non-polarization beam splitter is critical for the performance of our design.

Development of support tools for efficient construction of dynamic simulation program for engineering systems

International Nuclear Information System (INIS)

Gofuku, Akio

1993-01-01

In this study, two support tools are developed for construction of a dynamic simulation program for engineering systems (especially nuclear systems) by combining software modules. These are (1) a sub-system to support the module selection suitable for dynamic simulation and (2) a graphical user interface to support visual construction of simulation programs. The support tools are designed to be independent on the conception of software modules (data communication methods between modules). In the module selection sub-system of item 1, a module is characterized beforehand by keywords for several criteria. The similarity between the characteristic of requested module by users and that of registered modules in the module library is estimated by a weighted average of similarity indexes for criteria. In the module selection sub-system, the weights are flexibly extracted from users by applying the analytic hierarchy process. The graphical user interface helps users to specify both calling order of modules and data transfer between two modules. The availability of the support tools is evaluated by several sample problems of module selection and dynamic simulation model construction. The support tools will be a strong tool for the efficient usage of software modules. (author)

Speech recognition from spectral dynamics

Indian Academy of Sciences (India)

Some of the history of gradual infusion of the modulation spectrum concept into Automatic recognition of speech (ASR) comes next, pointing to the relationship of modulation spectrum processing to wellaccepted ASR techniques such as dynamic speech features or RelAtive SpecTrAl (RASTA) filtering. Next, the frequency ...

Different effects of inorganic and dimethylated arsenic compounds on cell morphology, cytoskeletal organization, and DNA synthesis in cultured Chinese hamster V79 cells

Energy Technology Data Exchange (ETDEWEB)

Ochi, Takafumi; Nakajima, Fumie [Department of Environmental Toxicology, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa (Japan); Fukumori, Nobutaka [Department of Toxicology, Tokyo Metropolitan Research Laboratory of Public Health, Hyakuninchou, Shinjyuku (Japan)

1998-09-01

Changes in cytoskeletal organization of cultured V79 cells exposed to arsenite and dimethylarsinic acid (DMAA), a methylated derivative of inorganic arsenics, and related changes, such as mitotic arrest and induction of multinucleated cells, were investigated in comparison with their effects on DNA synthesis. DMAA caused mitotic arrest and induction of multinucleated cells with a delay of 12 h relative to the mitotic arrest. By contrast, arsenite at equitoxic concentrations to DMAA was less effective than DMAA in causing mitotic arrest and in inducing multinucleated cells. Post-mitotic incubation of cells arrested in metaphase by 6 h incubation with 10 mM DMAA showed that the incidence of multinucleated cells increased conversely with a rapid decrease in metaphase cells. This suggests that metaphase-arrested cells can escape from metaphase, resulting in the appearance of multinucleated cells. The mitotic arrest caused by DMAA was accompanied by disruption of the microtubule network. By contrast, both arsenite and DMAA did not cause disorganization of actin stress fibers even when incubated at concentrations that caused a marked retardation of cell growth. Cells exposed to arsenite for 6 h showed marked inhibition of DNA synthesis, whereas inhibition by DMAA was not observed. When incubation was prolonged by 18 h, the arsenite-induced inhibition of DNA synthesis was mitigated. By contrast, inhibition of DNA synthesis by DMAA occurred in parallel with an increase in the population of mitotic cells. These results suggest that DMAA caused growth retardation and morphological changes via disruption of the microtubule network, and that arsenite-induced retardation of cell growth and inhibition of DNA synthesis were not attributable to the cytoskeletal changes. (orig.) (orig.) With 7 figs., 31 refs.

Double-Wavelet Approach to Studying the Modulation Properties of Nonstationary Multimode Dynamics

DEFF Research Database (Denmark)

Sosnovtseva, Olga; Mosekilde, Erik; Pavlov, A.N.

2005-01-01

On the basis of double-wavelet analysis, the paper proposes a method to study interactions in the form of frequency and amplitude modulation in nonstationary multimode data series. Special emphasis is given to the problem of quantifying the strength of modulation for a fast signal by a coexisting...

Selective attention to phonology dynamically modulates initial encoding of auditory words within the left hemisphere.

Science.gov (United States)

Yoncheva, Yuliya; Maurer, Urs; Zevin, Jason D; McCandliss, Bruce D

2014-08-15

Selective attention to phonology, i.e., the ability to attend to sub-syllabic units within spoken words, is a critical precursor to literacy acquisition. Recent functional magnetic resonance imaging evidence has demonstrated that a left-lateralized network of frontal, temporal, and posterior language regions, including the visual word form area, supports this skill. The current event-related potential (ERP) study investigated the temporal dynamics of selective attention to phonology during spoken word perception. We tested the hypothesis that selective attention to phonology dynamically modulates stimulus encoding by recruiting left-lateralized processes specifically while the information critical for performance is unfolding. Selective attention to phonology was captured by manipulating listening goals: skilled adult readers attended to either rhyme or melody within auditory stimulus pairs. Each pair superimposed rhyming and melodic information ensuring identical sensory stimulation. Selective attention to phonology produced distinct early and late topographic ERP effects during stimulus encoding. Data-driven source localization analyses revealed that selective attention to phonology led to significantly greater recruitment of left-lateralized posterior and extensive temporal regions, which was notably concurrent with the rhyme-relevant information within the word. Furthermore, selective attention effects were specific to auditory stimulus encoding and not observed in response to cues, arguing against the notion that they reflect sustained task setting. Collectively, these results demonstrate that selective attention to phonology dynamically engages a left-lateralized network during the critical time-period of perception for achieving phonological analysis goals. These findings suggest a key role for selective attention in on-line phonological computations. Furthermore, these findings motivate future research on the role that neural mechanisms of attention may

Selective attention to phonology dynamically modulates initial encoding of auditory words within the left hemisphere

Science.gov (United States)

Yoncheva; Maurer, Urs; Zevin, Jason; McCandliss, Bruce

2015-01-01

Selective attention to phonology, i.e., the ability to attend to sub-syllabic units within spoken words, is a critical precursor to literacy acquisition. Recent functional magnetic resonance imaging evidence has demonstrated that a left-lateralized network of frontal, temporal, and posterior language regions, including the visual word form area, supports this skill. The current event-related potential (ERP) study investigated the temporal dynamics of selective attention to phonology during spoken word perception. We tested the hypothesis that selective atten tion to phonology dynamically modulates stimulus encoding by recruiting left-lateralized processes specifically while the information critical for performance is unfolding. Selective attention to phonology was captured by ma nipulating listening goals: skilled adult readers attended to either rhyme or melody within auditory stimulus pairs. Each pair superimposed rhyming and melodic information ensuring identical sensory stimulation. Selective attention to phonology produced distinct early and late topographic ERP effects during stimulus encoding. Data- driven source localization analyses revealed that selective attention to phonology led to significantly greater re cruitment of left-lateralized posterior and extensive temporal regions, which was notably concurrent with the rhyme-relevant information within the word. Furthermore, selective attention effects were specific to auditory stimulus encoding and not observed in response to cues, arguing against the notion that they reflect sustained task setting. Collectively, these results demonstrate that selective attention to phonology dynamically engages a left-lateralized network during the critical time-period of perception for achieving phonological analysis goals. These findings support the key role of selective attention to phonology in the development of literacy and motivate future research on the neural bases of the interaction between phonological

Atorvastatin from target screening attenuates endothelial cell tube formation and migration by regulating urokinase receptor-related signaling pathway and F/G actin

Directory of Open Access Journals (Sweden)

Li Wei

2017-02-01

Conclusion: We conclude that close regulatory machinery spans angiogenesis, uPAR signaling, and cytoskeletal transformation, and that uPAR modulator Ator can decrease the reorganization of actin cytoskeleton, which may lead to a new approach in angiogenesis.

The dosimetric impact of inversely optimized arc radiotherapy plan modulation for real-time dynamic MLC tracking delivery

International Nuclear Information System (INIS)

Falk, Marianne; Larsson, Tobias; Keall, Paul; Chul Cho, Byung; Aznar, Marianne; Korreman, Stine; Poulsen, Per; Munck af Rosenschoeld, Per

2012-01-01

Purpose: Real-time dynamic multileaf collimator (MLC) tracking for management of intrafraction tumor motion can be challenging for highly modulated beams, as the leaves need to travel far to adjust for target motion perpendicular to the leaf travel direction. The plan modulation can be reduced by using a leaf position constraint (LPC) that reduces the difference in the position of adjacent MLC leaves in the plan. The purpose of this study was to investigate the impact of the LPC on the quality of inversely optimized arc radiotherapy plans and the effect of the MLC motion pattern on the dosimetric accuracy of MLC tracking delivery. Specifically, the possibility of predicting the accuracy of MLC tracking delivery based on the plan modulation was investigated. Methods: Inversely optimized arc radiotherapy plans were created on CT-data of three lung cancer patients. For each case, five plans with a single 358 deg. arc were generated with LPC priorities of 0 (no LPC), 0.25, 0.5, 0.75, and 1 (highest possible LPC), respectively. All the plans had a prescribed dose of 2 Gy x 30, used 6 MV, a maximum dose rate of 600 MU/min and a collimator angle of 45 deg. or 315 deg. To quantify the plan modulation, an average adjacent leaf distance (ALD) was calculated by averaging the mean adjacent leaf distance for each control point. The linear relationship between the plan quality [i.e., the calculated dose distributions and the number of monitor units (MU)] and the LPC was investigated, and the linear regression coefficient as well as a two tailed confidence level of 95% was used in the evaluation. The effect of the plan modulation on the performance of MLC tracking was tested by delivering the plans to a cylindrical diode array phantom moving with sinusoidal motion in the superior-inferior direction with a peak-to-peak displacement of 2 cm and a cycle time of 6 s. The delivery was adjusted to the target motion using MLC tracking, guided in real-time by an infrared optical system

Modelling the heat dynamics of building integrated and ventilated photovoltaic modules

DEFF Research Database (Denmark)

Friling, N.; Jimenez, M.J.; Bloem, H.

2009-01-01

the heat transfer from the PV module. The experiment and data originate from a test reference module the EC-JRC Ispra. The set-up provides the opportunity of changing physical parameters, the ventilation speed and the type of air flow, and this makes it possible to determine the preferable set......, are applied in the set-up combined with high level of air flow. The improved description by the model is mainly seen in periods with high solar radiation....

Sigma-delta modulator modeling analysis and design

Energy Technology Data Exchange (ETDEWEB)

Ge Binjie; Wang Xin' an; Zhang Xing; Feng Xiaoxing; Wang Qingqin, E-mail: wangxa@szpku.edu.c [Key Laboratory of Integrated Microsystem Science and Engineering Applications, Shenzhen Graduate School of Peking University, Shenzhen 518055 (China)

2010-09-15

This paper introduces a new method for SC sigma-delta modulator modeling. It studies the integrator's different equivalent circuits in the integrating and sampling phases. This model uses the OP-AMP input pair's tail current (I{sub 0}) and overdrive voltage (v{sub on}) as variables. The modulator's static and dynamic errors are analyzed. A group of optimized I{sub 0} and v{sub on} for maximum SNR and power x area ratio can be obtained through this model. As examples, a MASH21 modulator for digital audio and a second order modulator for RFID baseband are implemented and tested, and they can achieve 91 dB and 72 dB respectively, which verifies the modeling and design criteria. (semiconductor integrated circuits)

Neutrophil microparticle production and inflammasome activation by hyperglycemia due to cytoskeletal instability.

Science.gov (United States)

Thom, Stephen R; Bhopale, Veena M; Yu, Kevin; Huang, Weiliang; Kane, Maureen A; Margolis, David J

2017-11-03

Microparticles are lipid bilayer-enclosed vesicles produced by cells under oxidative stress. MP production is elevated in patients with diabetes, but the underlying cellular mechanisms are poorly understood. We hypothesized that raising glucose above the physiological level of 5.5 mm would stimulate leukocytes to produce MPs and activate the nucleotide-binding domain, leucine-rich repeat pyrin domain-containing 3 (NLRP3) inflammasome. We found that when incubated in buffer with up to 20 mm glucose, human and murine neutrophils, but not monocytes, generate progressively more MPs with high interleukin (IL)-1β content. Enhanced MP production required generation of reactive chemical species by mitochondria, NADPH oxidase, and type 2 nitric-oxide synthase (NOS-2) and resulted in S -nitrosylation of actin. Depleting cells of capon (C-terminal PDZ ligand of neuronal nitric-oxide synthase protein), apoptosis-associated speck-like protein containing C-terminal caspase recruitment domain (ASC), or pro-IL-1β prevented the hyperglycemia-induced enhancement of reactive species production, MP generation, and IL-1β synthesis. Additional components required for these responses included inositol 1,3,5-triphosphate receptors, PKC, and enhancement of filamentous-actin turnover. Numerous proteins become localized to short filamentous actin in response to S -nitrosylation, including vasodilator-stimulated phosphoprotein, focal adhesion kinase, the membrane phospholipid translocation enzymes flippase and floppase, capon, NLRP3, and ASC. We conclude that an interdependent oxidative stress response to hyperglycemia perturbs neutrophil cytoskeletal stability leading to MP production and IL-1β synthesis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Toward structural dynamics: protein motions viewed by chemical shift modulations and direct detection of C'N multiple-quantum relaxation.

Science.gov (United States)

Mori, Mirko; Kateb, Fatiha; Bodenhausen, Geoffrey; Piccioli, Mario; Abergel, Daniel

2010-03-17

Multiple quantum relaxation in proteins reveals unexpected relationships between correlated or anti-correlated conformational backbone dynamics in alpha-helices or beta-sheets. The contributions of conformational exchange to the relaxation rates of C'N coherences (i.e., double- and zero-quantum coherences involving backbone carbonyl (13)C' and neighboring amide (15)N nuclei) depend on the kinetics of slow exchange processes, as well as on the populations of the conformations and chemical shift differences of (13)C' and (15)N nuclei. The relaxation rates of C'N coherences, which reflect concerted fluctuations due to slow chemical shift modulations (CSMs), were determined by direct (13)C detection in diamagnetic and paramagnetic proteins. In well-folded proteins such as lanthanide-substituted calbindin (CaLnCb), copper,zinc superoxide dismutase (Cu,Zn SOD), and matrix metalloproteinase (MMP12), slow conformational exchange occurs along the entire backbone. Our observations demonstrate that relaxation rates of C'N coherences arising from slow backbone dynamics have positive signs (characteristic of correlated fluctuations) in beta-sheets and negative signs (characteristic of anti-correlated fluctuations) in alpha-helices. This extends the prospects of structure-dynamics relationships to slow time scales that are relevant for protein function and enzymatic activity.

Membrane tension regulates clathrin-coated pit dynamics

Science.gov (United States)

Liu, Allen

2014-03-01

Intracellular organization depends on close communication between the extracellular environment and a network of cytoskeleton filaments. The interactions between cytoskeletal filaments and the plasma membrane lead to changes in membrane tension that in turns help regulate biological processes. Endocytosis is thought to be stimulated by low membrane tension and the removal of membrane increases membrane tension. While it is appreciated that the opposing effects of exocytosis and endocytosis have on keeping plasma membrane tension to a set point, it is not clear how membrane tension affects the dynamics of clathrin-coated pits (CCPs), the individual functional units of clathrin-mediated endocytosis. Furthermore, although it was recently shown that actin dynamics counteracts membrane tension during CCP formation, it is not clear what roles plasma membrane tension plays during CCP initiation. Based on the notion that plasma membrane tension is increased when the membrane area increases during cell spreading, we designed micro-patterned surfaces of different sizes to control the cell spreading sizes. Total internal reflection fluorescence microscopy of living cells and high content image analysis were used to quantify the dynamics of CCPs. We found that there is an increased proportion of CCPs with short (<20s) lifetime for cells on larger patterns. Interestingly, cells on larger patterns have higher CCP initiation density, an effect unexpected based on the conventional view of decreasing endocytosis with increasing membrane tension. Furthermore, by analyzing the intensity profiles of CCPs that were longer-lived, we found CCP intensity decreases with increasing cell size, indicating that the CCPs are smaller with increasing membrane tension. Finally, disruption of actin dynamics significantly increased the number of short-lived CCPs, but also decreased CCP initiation rate. Together, our study reveals new mechanistic insights into how plasma membrane tension regulates

Effect of tune modulation on the transverse stability of storage ring

International Nuclear Information System (INIS)

Yang Jiancheng; Xia Jiawen; Wu Junxia; Xia Guoxing; Liu Wei; Yin Xuejun; Liu Yong; Zhou Xuemei; Mao Lijun

2004-01-01

The transverse stability is a critical issue in circular accelerator. In this paper, authors analysed the effect of tune modulation on a FODO lattice with sextupole nonlinear through estimating the dynamic aperture including the influence of the distortion along the phase. It turned out that the tune modulation decreases the stability of particle in storage ring, the extent of this decrease depends largely on the amplitude and tune of modulation. (author)

Modulation of dynamic modes by interplay between positive and negative feedback loops in gene regulatory networks

Science.gov (United States)

Wang, Liu-Suo; Li, Ning-Xi; Chen, Jing-Jia; Zhang, Xiao-Peng; Liu, Feng; Wang, Wei

2018-04-01

A positive and a negative feedback loop can induce bistability and oscillation, respectively, in biological networks. Nevertheless, they are frequently interlinked to perform more elaborate functions in many gene regulatory networks. Coupled positive and negative feedback loops may exhibit either oscillation or bistability depending on the intensity of the stimulus in some particular networks. It is less understood how the transition between the two dynamic modes is modulated by the positive and negative feedback loops. We developed an abstract model of such systems, largely based on the core p53 pathway, to explore the mechanism for the transformation of dynamic behaviors. Our results show that enhancing the positive feedback may promote or suppress oscillations depending on the strength of both feedback loops. We found that the system oscillates with low amplitudes in response to a moderate stimulus and switches to the on state upon a strong stimulus. When the positive feedback is activated much later than the negative one in response to a strong stimulus, the system exhibits long-term oscillations before switching to the on state. We explain this intriguing phenomenon using quasistatic approximation. Moreover, early switching to the on state may occur when the system starts from a steady state in the absence of stimuli. The interplay between the positive and negative feedback plays a key role in the transitions between oscillation and bistability. Of note, our conclusions should be applicable only to some specific gene regulatory networks, especially the p53 network, in which both oscillation and bistability exist in response to a certain type of stimulus. Our work also underscores the significance of transient dynamics in determining cellular outcome.

Mechanical Cushion Design Influence on Cylinder Dynamics

DEFF Research Database (Denmark)

Borghi, Massimo; Milani, Massimo; Conrad, Finn

2005-01-01

The paper deals with the simulation and the experimental verification of the dynamic behaviour of a linear actuator equipped with different configurations of mechanical cushion. A numerical model, developed and tailored to describe the influence of different modulation of the discharged flow....... experimental comparison, involving the piston velocity and the cylinder chambers pressure. After, with the aim of highlighting the effect of mechanical cushions design on a two effect linear actuator dynamic performances, the characteristics modulation of four alternative cushioning systems are determined...

Inhibition of phospholipase C disrupts cytoskeletal organization and gravitropic growth in Arabidopsis roots.

Science.gov (United States)

Andreeva, Zornitza; Barton, Deborah; Armour, William J; Li, Min Y; Liao, Li-Fen; McKellar, Heather L; Pethybridge, Kylie A; Marc, Jan

2010-10-01

The phospholipase protein superfamily plays an important role in hormonal signalling and cellular responses to environmental stimuli. There is also growing evidence for interactions between phospholipases and the cytoskeleton. In this report we used a pharmacological approach to investigate whether inhibiting a member of the phospholipase superfamily, phospholipase C (PLC), affects microtubules and actin microfilaments as well as root growth and morphology of Arabidopsis thaliana seedlings. Inhibiting PLC activity using the aminosteroid U73122 significantly inhibited root elongation and disrupted root morphology in a concentration-dependent manner, with the response being saturated at 5 μM, whereas the inactive analogue U73343 was ineffective. The primary root appeared to lose growth directionality accompanied by root waving and formation of curls. Immunolabelling of roots exposed to increasingly higher U73122 concentrations revealed that the normal transverse arrays of cortical microtubules in the elongation zone became progressively more disorganized or depolymerized, with the disorganization appearing within 1 h of incubation. Likewise, actin microfilament arrays also were disrupted. Inhibiting PLC using an alternative inhibitor, neomycin, caused similar disruptions to both cytoskeletal organization and root morphology. In seedlings gravistimulated by rotating the culture plates by 90°, both U73122 and neomycin disrupted the normal gravitropic growth of roots and etiolated hypocotyls. The effects of PLC inhibitors are therefore consistent with the notion that, as with phospholipases A and D, PLC likewise interacts with the cytoskeleton, alters growth morphology, and is involved in gravitropism.

Optimal Modulator with Loudspeaker Parameter Inclusion

DEFF Research Database (Denmark)

Dahl, Nicolai J.; Iversen, Niels Elkjær; Knott, Arnold

2017-01-01

Today, most class-D amplifier designs are able to deliver high efficiency and low distortion. However, the effect ofparasitic components and speaker dynamics are not taken into account, resulting in a degradation of the performance.This paper proposes a new PWM modulator which is able to capture ...

A novel research approach on the dynamic properties of photogenerated charge carriers at Ag{sub 2}S quantum-dots-sensitized TiO{sub 2} films by a frequency-modulated surface photovoltage technology

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yu; Zhang, Wei [Liaoning Key Laboratory for Green Synthesis and Preparative Chemistry of Advanced Materials, College of Chemistry, Liaoning University, Shenyang 110036 (China); Xie, Tengfeng; Wang, Dejun [College of Chemistry, Jilin University, Changchun 130012 (China); Song, Xi-Ming, E-mail: songlab@lnu.edu.cn [Liaoning Key Laboratory for Green Synthesis and Preparative Chemistry of Advanced Materials, College of Chemistry, Liaoning University, Shenyang 110036 (China)

2013-09-01

Graphical abstract: The changed SPV with chopping frequencies indicate the separation speeds of photogenerated charge carriers in different films. - Highlights: • Ag{sub 2}S-sensitized TiO{sub 2} films show good photoelectric responses in visible-light region. • Frequency-modulated SPV give dynamic information and evidence of Ag{sub 2}S QDSSCs’ performance. • Frequency-modulated SPV can supply complementary information in the study of Ag{sub 2}S ODSSCs. - Abstract: Ag{sub 2}S quantum-dots-sensitized TiO{sub 2} films with different amount of Ag{sub 2}S were fabricated by a successive ionic layer adsorption and reaction (SILAR) method. The separation and transport of photogenerated charge carriers at different spectral regions were studied by the frequency-modulated surface photovoltage technology. Some novel dynamic information of photogenerated charge carriers in a wide spectral range is found. The results indicate that the rate and direction of separation (diffusion) for photogenerated charge carriers are closely related to the performance of quantum-dots-sensitized solar cells (QDSSCs) based on the Ag{sub 2}S/TiO{sub 2} nano-structure.

A Retrospective on Modulated Wavy Vortex Flow

OpenAIRE

Gorman, Michael; Swinney, Harry

2009-01-01

A fluid dynamics video of the Modulated Wavy Vortex Flow state of Taylor-Couette flow with the outer cylinder fixed is presented. This state precedes the transition to turbulence, which is more gradual than that for other fluid systems.

DMPD: Modulation of Toll-interleukin 1 receptor mediated signaling. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 15662540 Modulation of Toll-interleukin 1 receptor mediated signaling. Li X, Qin J.... J Mol Med. 2005 Apr;83(4):258-66. Epub 2005 Jan 21. (.png) (.svg) (.html) (.csml) Show Modulation of Toll-i...nterleukin 1 receptor mediated signaling. PubmedID 15662540 Title Modulation of Toll-interleukin 1 receptor

Thermal equilibrium control by frequent bang-bang modulation.

Science.gov (United States)

Yang, Cheng-Xi; Wang, Xiang-Bin

2010-05-01

In this paper, we investigate the non-Markovian heat transfer between a weakly damped harmonic oscillator (system) and a thermal bath. When the system is initially in a thermal state and not correlated with the environment, the mean energy of the system always first increases, then oscillates, and finally reaches equilibrium with the bath, no matter what the initial temperature of the system is. Moreover, the heat transfer between the system and the bath can be controlled by fast bang-bang modulation. This modulation does work on the system, and temporarily inverts the direction of heat flow. In this case, the common sense that heat always transfers from hot to cold does not hold any more. At the long time scale, a new dynamic equilibrium is established between the system and the bath. At this equilibrium, the energy of the system can be either higher or lower than its normal equilibrium value. A comprehensive analysis of the relationship between the dynamic equilibrium and the parameters of the modulation as well as the environment is presented.

Module generator of plans for dynamic processes; Modulo generdor de planes para procesos dinamicos

Energy Technology Data Exchange (ETDEWEB)

Reyes B, Alberto; Fernandez J, Jose L [Instituto de Investigaciones Electricas, Cuernavaca, Morelos (Mexico)

2002-07-01

This work describes the generating module of plans (Geplan) as a part of the project: Development of Techniques of Intelligent Planning for Dynamic Processes, based on techniques of artificial intelligence, and that is being developed in the Gerencia de Control e Instrumentacion the Instituto de Investigaciones Electricas (IIE). The study case corresponds to the elaboration of a plan to help the plant operators in the task of taking a combined cycle central (CCC) to a stable state of operation given a specific load level. The architecture of the module generator of plans is presented and the codification of the actions allowed (ACT) is illustrated by means of rules, in addition the challenges that are due to face so that the system operates in line with the process. Also the technical aspects of the generator of plans, as well as the benefits and expectations of their use in any CCC are mentioned. [Spanish] En este trabajo se describe el modulo generador de planes (Geplan) como parte del proyecto Desarrollo de Tecnicas de Planificacion Inteligente para Procesos Dinamicos, basado en tecnicas de inteligencia Artificial, y que estan desarrollandose en la Gerencia de Control e Instrumentacion del Instituto de Investigaciones Electrica (IIE). El caso de estudio corresponde a la elaboracion de un plan para asistir a los operadores de planta en la tarea de llevar una central de ciclo combinado (CCC) a un estado estable de operacion dedo un nivel de carga especifico. Se presenta la arquitectura del modulo generador de planes y se ilustra la codificacion de las acciones permitidas (ACT) mediante reglas, ademas los retos que se deben enfrentar para que el sistema opere en linea con el proceso. Tambien se mencionan los aspectos tecnicos del generador de planes, asi como los beneficios y expectativas de su uso en cualquier CCC.

Antinuclear, Cytoskeletal, Antineuronal Antibodies in the Serum Samples of Children with Tic Disorders and Obsessive Compulsive Disorders

Directory of Open Access Journals (Sweden)

Işık Görker

2011-11-01

Full Text Available streptococcus infections in the development of tic and obsessive compulsive disorders (OCD is controversial. The autoimmune hypothesis states that during infection, formation of autoantibodies leads to an autoimmune disorder, which in turn results in movement disorders, tic disorders and/or OCD. In order to test this hypothesis, we assayed these antibodies in children and adolescents diagnosed with tic disorders and/or OCD.Material and Methods: Children and adolescents who were diagnosed with either tic disorders or OCD according to DSM-IV criteria (n=28, were compared with healthy controls (n=15 having similar age and gender characteristics. Regardless of a streptococcus infection history, serum samples of all patients and controls underwent antinuclear, cytoskeletal, and antineuronal antibody assay using indirect immunofluorescence.Results: The rates of antinuclear antibody positivity were 21% and 20% in the patient and control groups respectively (p>0.05. Antineuronal antibody was positive in 2 (7% of 28 patients versus in 1 (6% of 15 controls (p>0.05.Conclusion: These results suggest that such antibodies may not be involved in the pathogenesis of tic disorders/OCD.

The Na+–H+ exchanger-1 induces cytoskeletal changes involving reciprocal RhoA and Rac1 signaling, resulting in motility and invasion in MDA-MB-435 cells

International Nuclear Information System (INIS)

Paradiso, Angelo; Cardone, Rosa Angela; Bellizzi, Antonia; Bagorda, Anna; Guerra, Lorenzo; Tommasino, Massimo; Casavola, Valeria; Reshkin, Stephan J

2004-01-01

An increasing body of evidence shows that the tumour microenvironment is essential in driving neoplastic progression. The low serum component of this microenvironment stimulates motility/invasion in human breast cancer cells via activation of the Na + –H + exchanger (NHE) isoform 1, but the signal transduction systems that underlie this process are still poorly understood. We undertook the present study to elucidate the role and pattern of regulation by the Rho GTPases of this serum deprivation-dependent activation of both NHE1 and subsequent invasive characteristics, such as pseudopodia and invadiopodia protrusion, directed cell motility and penetration of normal tissues. The present study was performed in a well characterized human mammary epithelial cell line representing late stage metastatic progression, MDA-MB-435. The activity of RhoA and Rac1 was modified using their dominant negative and constitutively active mutants and the activity of NHE1, cell motility/invasion, F-actin content and cell shape were measured. We show for the first time that serum deprivation induces NHE1-dependent morphological and cytoskeletal changes in metastatic cells via a reciprocal interaction of RhoA and Rac1, resulting in increased chemotaxis and invasion. Deprivation changed cell shape by reducing the amount of F-actin and inducing the formation of leading edge pseudopodia. Serum deprivation inhibited RhoA activity and stimulated Rac1 activity. Rac1 and RhoA were antagonistic regulators of both basal and stimulated tumour cell NHE1 activity. The regulation of NHE1 activity by RhoA and Rac1 in both conditions was mediated by an alteration in intracellular proton affinity of the exchanger. Interestingly, the role of each of these G-proteins was reversed during serum deprivation; basal NHE1 activity was regulated positively by RhoA and negatively by Rac1, whereas RhoA negatively and Rac1 positively directed the stimulation of NHE1 during serum deprivation. Importantly, the same

Comparative study of cyanotoxins affecting cytoskeletal and chromatin structures in CHO-K1 cells.

Science.gov (United States)

Gácsi, Mariann; Antal, Otilia; Vasas, Gábor; Máthé, Csaba; Borbély, György; Saker, Martin L; Gyori, János; Farkas, Anna; Vehovszky, Agnes; Bánfalvi, Gáspár

2009-06-01

In this study we compared the effects of the two frequently occuring and most dangerous cyanobacterial toxins on the cellular organization of microfilaments, microtubules and on the chromatin structure in Chinese hamster ovary (CHO-K1) cells. These compounds are the widely known microcystin-LR (MC-LR) and cylindrospermopsin (CYN) classified as the highest-priority cyanotoxin. Toxic effects were tested in a concentration and time dependent manner. The hepatotoxic MC-LR did not cause significant cytotoxicity on CHO-K1 cells under 20 microM, but caused apoptotic changes at higher concentrations. Apoptotic shrinkage was associated with the shortening and loss of actin filaments and with a concentration dependent depolymerization of microtubules. No necrosis was observed over the concentration range (1-50 microM MC-LR) tested. Cylindrospermopsin did cause apoptosis at low concentrations (1-2 microM) and over short exposure periods (12h). Necrosis was observed at higher concentrations (5-10 microM) and following longer exposure periods (24 or 48h). Cyanotoxins also affected the chromatin structure. The condensation process was inhibited by MC-LR at a later stage and manifested as broken elongated prechromosomes. CYN inhibited chromatin condensation at the early fibrillary stage leading to blurred fluorescent images of apoptotic bodies and preventing the formation of metaphase chromosomes. Cylindrospermopsin exhibited a more pronounced toxic effect causing cytoskeletal and nuclear changes as well as apoptotic and necrotic alterations.

Dynamics of wide and snake-like pulses in coupled Schrödinger equations with full-modulated nonlinearities

Energy Technology Data Exchange (ETDEWEB)

Yomba, Emmanuel, E-mail: emmanuel.yomba@csun.edu; Zakeri, Gholam-Ali, E-mail: ali.zakeri@csun.edu

2016-02-05

We investigate the existence of various solitary wave solutions in coupled Schrödinger equations with specific cubic and quintic nonlinearities. This system arises in wave propagation in fiber optics with focusing and defocusing with modulated nonlinearities. We obtain front–front, bright–bright, dark–dark, and dark–bright like solitons using a direct approach, and then, by reducing the system of equations to a single auxiliary equation of a Duffing-type ordinary differential equation, we provide a large class of Jacobi-elliptic solutions. These solutions are presented in the exact form and analyzed. We find a class of wide localized and snake-like (in both space and time) vector solitons. One of the novel aspects of this study is that we have shown that the qualitative behavior of the solutions is independent of the choice of similarity variables. Numerical results show that the solutions of the above system are stable with up to 10% white noises. - Highlights: • Dynamics of wide and snake-like pulses is analyzed for coupled Schrödinger equations. • Qualitative appearance of solutions is analyzed using various similarity variables. • Effect of change in parameter-values on dynamics of the solutions is investigated. • Vectors front–front, bright–bright, dark–dark and dark–bright solitons are obtained.

Promoting neuroregeneration by applying dynamic magnetic fields to a novel nanomedicine: Superparamagnetic iron oxide (SPIO)-gold nanoparticles bounded with nerve growth factor (NGF).

Science.gov (United States)

Yuan, Muzhaozi; Wang, Ya; Qin, Yi-Xian

2018-04-05

Neuroregeneration imposes a significant challenge in neuroscience for treating neurodegenerative diseases. The objective of this study is to evaluate the hypothesis that the nerve growth factor (NGF) functionalized superparamagnetic iron oxide (SPIO)-gold (Au) nanomedicine can stimulate the neuron growth and differentiation under external magnetic fields (MFs), and dynamic MFs outperform their static counterparts. The SPIO-Au core-shell nanoparticles (NPs) (Diameter: 20.8 nm) possessed advantages such as uniform quasi-spherical shapes, narrow size distribution, excellent stabilities, and low toxicity (viability >96% for 5 days). NGF functionalization has enhanced the cellular uptake. The promotion of neuronal growth and orientation using NGF functionalized SPIO-Au NPs, driven by both the static and dynamic MFs, were revealed experimentally on PC-12 cells and theoretically on a cytoskeletal force model. More importantly, dynamic MFs via rotation performed better than the static ones, i.e., the cellular differentiation ratio increased 58%; the neurite length elongation increased 63%. Copyright © 2018 Elsevier Inc. All rights reserved.

Integrative Analysis of Subcellular Quantitative Proteomics Studies Reveals Functional Cytoskeleton Membrane-Lipid Raft Interactions in Cancer.

Science.gov (United States)

Shah, Anup D; Inder, Kerry L; Shah, Alok K; Cristino, Alexandre S; McKie, Arthur B; Gabra, Hani; Davis, Melissa J; Hill, Michelle M

2016-10-07

Lipid rafts are dynamic membrane microdomains that orchestrate molecular interactions and are implicated in cancer development. To understand the functions of lipid rafts in cancer, we performed an integrated analysis of quantitative lipid raft proteomics data sets modeling progression in breast cancer, melanoma, and renal cell carcinoma. This analysis revealed that cancer development is associated with increased membrane raft-cytoskeleton interactions, with ∼40% of elevated lipid raft proteins being cytoskeletal components. Previous studies suggest a potential functional role for the raft-cytoskeleton in the action of the putative tumor suppressors PTRF/Cavin-1 and Merlin. To extend the observation, we examined lipid raft proteome modulation by an unrelated tumor suppressor opioid binding protein cell-adhesion molecule (OPCML) in ovarian cancer SKOV3 cells. In agreement with the other model systems, quantitative proteomics revealed that 39% of OPCML-depleted lipid raft proteins are cytoskeletal components, with microfilaments and intermediate filaments specifically down-regulated. Furthermore, protein-protein interaction network and simulation analysis showed significantly higher interactions among cancer raft proteins compared with general human raft proteins. Collectively, these results suggest increased cytoskeleton-mediated stabilization of lipid raft domains with greater molecular interactions as a common, functional, and reversible feature of cancer cells.

All-optical modulation based on electromagnetically induced transparency

International Nuclear Information System (INIS)

Fountoulakis, Antonios; Terzis, Andreas F.; Paspalakis, Emmanuel

2010-01-01

We numerically investigate the implementation of all-optical absorption modulation of electromagnetic pulses by a medium that exhibits electromagnetically induced transparency. The quantum system is modelled as a three-level Λ-type system that interacts with two electromagnetic pulses, a probe pulse and a coupling pulse. The dynamics of the system is described by the coupled Maxwell-density matrix equations, and we explore the dependence of the optical modulation efficiency on the parameters of the system.

A comprehensive dynamic modeling approach for giant magnetostrictive material actuators

International Nuclear Information System (INIS)

Gu, Guo-Ying; Zhu, Li-Min; Li, Zhi; Su, Chun-Yi

2013-01-01

In this paper, a comprehensive modeling approach for a giant magnetostrictive material actuator (GMMA) is proposed based on the description of nonlinear electromagnetic behavior, the magnetostrictive effect and frequency response of the mechanical dynamics. It maps the relationships between current and magnetic flux at the electromagnetic part to force and displacement at the mechanical part in a lumped parameter form. Towards this modeling approach, the nonlinear hysteresis effect of the GMMA appearing only in the electrical part is separated from the linear dynamic plant in the mechanical part. Thus, a two-module dynamic model is developed to completely characterize the hysteresis nonlinearity and the dynamic behaviors of the GMMA. The first module is a static hysteresis model to describe the hysteresis nonlinearity, and the cascaded second module is a linear dynamic plant to represent the dynamic behavior. To validate the proposed dynamic model, an experimental platform is established. Then, the linear dynamic part and the nonlinear hysteresis part of the proposed model are identified in sequence. For the linear part, an approach based on axiomatic design theory is adopted. For the nonlinear part, a Prandtl–Ishlinskii model is introduced to describe the hysteresis nonlinearity and a constrained quadratic optimization method is utilized to identify its coefficients. Finally, experimental tests are conducted to demonstrate the effectiveness of the proposed dynamic model and the corresponding identification method. (paper)

Split coaxial RFQ structure with modulated vanes

International Nuclear Information System (INIS)

Arai, S.

1983-10-01

A new split coaxial RFO structure with modulated vanes is proposed. The structure is designed to accelerate 238 U 4+ from 1.68 keV/u to 45.1 keV/u at frequency of 12.5 MHz. The cavity is 1.6 m in diameter and 8 m in length. The cavity consists of four cavity modules divided by three stems which support horizontal and vertical vanes periodically and alternatively. At the same time, problems on the beam dynamics and design procedures are described and discussed. (orig.)

Emission Spectrum Property of Modulated Atom-Field Coupling System

International Nuclear Information System (INIS)

Gao Yun-Feng; Feng Jian; Li Yue-Ke

2013-01-01

The emission spectrum of a two-level atom interacting with a single mode radiation field in the case of periodic oscillation coupling coefficient is investigated. A general expression for the emission spectrum is derived. The numerical results for the initial field in pure number stare are calculated. It is found that the effect of the coupling coefficient modulation on the spectral structure is very obvious in the case of a low modulation frequency and larger amplitude when the initial field is vacuum, which is potentially useful for exploring a modulated light source. (electromagnetism, optics, acoustics, heat transfer, classical mechanics, and fluid dynamics)

Influence of atomization quality modulation on flame dynamics in a hypergolic rocket engine

Directory of Open Access Journals (Sweden)

Moritz Schulze

2016-09-01

Full Text Available For the numerical evaluation of the thermoacoustic stability of rocket engines often hybrid methods are applied, which separate the computation of wave propagation in the combustor from the analysis of the flame response to acoustic perturbations. Closure requires a thermoacoustic feedback model which provides the heat release fluctuation in the source term of the employed wave transport equations. The influence of the acoustic fluctuations in the combustion chamber on the heat release fluctuations from the modulation of the atomization of the propellants in a hypergolic upper stage rocket engine is studied. Numerical modeling of a single injector provides the time mean reacting flow field. A network of transfer functions representing all aspects relevant for the feedback model is presented. Analytical models for the injector admittances and for the atomization transfer functions are provided. The dynamics of evaporation and combustion are studied numerically and the numerical results are analyzed. An analytical approximation of the computed flame transfer function is combined with the analytical models for the injector and the atomization quality to derive the feedback model for the wave propagation code. The evaluation of this model on the basis of the Rayleigh index reveals the thermoacoustic driving potential originating from the fluctuating spray quality.

Development of e-module combining science process skills and dynamics motion material to increasing critical thinking skills and improve student learning motivation senior high school

Directory of Open Access Journals (Sweden)

Fengky Adie Perdana

2017-02-01

Full Text Available Learning media is one of the most components in the teaching and learning process. This research was conducted to design and develop the electronic modules combining science process skills and dynamics motion content for increasing critical thinking skills and improve student learning motivation for senior high school. The Methods used in this research is Research and Development (R&D. Model research and development using a research 4D Thiagarajan model. Physics module was developed using science process skills approach: observing, formulating the problem, formulating a hypothesis, identify variables, conduct experiments, analyse the data, summarise and communicate. The results showed that: 1 the electronics module has been developed by integrating the science process skills for enhancing critical thinking skills and student motivation. 2 Electronic Module Physics-based science process skills meet the criteria very well, judging from the results of validation content, validation media, validation of peer education and practitioners, with an average value of 3.80 is greater than the minimum eligibility 3.78. 3 effectiveness the modules of science process skills got N-gain value obtained from a large trial in grade samples of 0.67 and 0.59 in the control group were categorised as moderate. 4 Implementation of electronic modules Physics-based science process skills is considered an effective to enhance the students' motivation. Statistical analysis showed a significance value of 0.027 is lower than the significance level α = 0.05, this means that there are significant differences between learning motivation grade sample and the control class. As a result of analysis data obtained from the research, it was seen that the students' motivation that uses Physics module based science process skills better than conventional learning.

Revealing Pathway Dynamics in Heart Diseases by Analyzing Multiple Differential Networks.

Directory of Open Access Journals (Sweden)

Xiaoke Ma

2015-06-01

Full Text Available Development of heart diseases is driven by dynamic changes in both the activity and connectivity of gene pathways. Understanding these dynamic events is critical for understanding pathogenic mechanisms and development of effective treatment. Currently, there is a lack of computational methods that enable analysis of multiple gene networks, each of which exhibits differential activity compared to the network of the baseline/healthy condition. We describe the iMDM algorithm to identify both unique and shared gene modules across multiple differential co-expression networks, termed M-DMs (multiple differential modules. We applied iMDM to a time-course RNA-Seq dataset generated using a murine heart failure model generated on two genotypes. We showed that iMDM achieves higher accuracy in inferring gene modules compared to using single or multiple co-expression networks. We found that condition-specific M-DMs exhibit differential activities, mediate different biological processes, and are enriched for genes with known cardiovascular phenotypes. By analyzing M-DMs that are present in multiple conditions, we revealed dynamic changes in pathway activity and connectivity across heart failure conditions. We further showed that module dynamics were correlated with the dynamics of disease phenotypes during the development of heart failure. Thus, pathway dynamics is a powerful measure for understanding pathogenesis. iMDM provides a principled way to dissect the dynamics of gene pathways and its relationship to the dynamics of disease phenotype. With the exponential growth of omics data, our method can aid in generating systems-level insights into disease progression.

Dynamic Analysis of Hammer Mechanism "Twin Hammer" of Impact Wrench

Science.gov (United States)

Konečný, M.; Slavík, J.

This paper describes function of the hammer mechanism "Twin hammer" the impact wrench, calculation of dynamic forces exerted on the mechanism and determining the contact pressures between the parts of the mechanism. The modelling of parts was performed in system Pro ENGINEER—standard. The simulation and finding dynamic forces was performed in advanced module Pro ENGINEER—mechanism design and finding contacts pressures in modul Pro ENGENEER—mechanica.

The cytoskeleton as a novel therapeutic target for old neurodegenerative disorders.

Science.gov (United States)

Eira, Jessica; Silva, Catarina Santos; Sousa, Mónica Mendes; Liz, Márcia Almeida

2016-06-01

Cytoskeleton defects, including alterations in microtubule stability, in axonal transport as well as in actin dynamics, have been characterized in several unrelated neurodegenerative conditions. These observations suggest that defects of cytoskeleton organization may be a common feature contributing to neurodegeneration. In line with this hypothesis, drugs targeting the cytoskeleton are currently being tested in animal models and in human clinical trials, showing promising effects. Drugs that modulate microtubule stability, inhibitors of posttranslational modifications of cytoskeletal components, specifically compounds affecting the levels of tubulin acetylation, and compounds targeting signaling molecules which regulate cytoskeleton dynamics, constitute the mostly addressed therapeutic interventions aiming at preventing cytoskeleton damage in neurodegenerative disorders. In this review, we will discuss in a critical perspective the current knowledge on cytoskeleton damage pathways as well as therapeutic strategies designed to revert cytoskeleton-related defects mainly focusing on the following neurodegenerative disorders: Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Amyotrophic Lateral Sclerosis and Charcot-Marie-Tooth Disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Documentation of the dynamic parameter, water-use, stream and lake flow routing, and two summary output modules and updates to surface-depression storage simulation and initial conditions specification options with the Precipitation-Runoff Modeling System (PRMS)

Science.gov (United States)

Regan, R. Steve; LaFontaine, Jacob H.

2017-10-05

This report documents seven enhancements to the U.S. Geological Survey (USGS) Precipitation-Runoff Modeling System (PRMS) hydrologic simulation code: two time-series input options, two new output options, and three updates of existing capabilities. The enhancements are (1) new dynamic parameter module, (2) new water-use module, (3) new Hydrologic Response Unit (HRU) summary output module, (4) new basin variables summary output module, (5) new stream and lake flow routing module, (6) update to surface-depression storage and flow simulation, and (7) update to the initial-conditions specification. This report relies heavily upon U.S. Geological Survey Techniques and Methods, book 6, chapter B7, which documents PRMS version 4 (PRMS-IV). A brief description of PRMS is included in this report.

Mode change design for capacity modulation in reciprocating compressor

International Nuclear Information System (INIS)

Bae, Young Ju; Kim, Jin Kook; Kim, Jong Bong; Chang, Young June

2008-01-01

Due to environmental issues, the development of low energy consumption products has become one of the main topics in the home appliance industry. The energy consumption of a refrigerator depends on the efficiency of its compressor as well as on the refrigerator cycle design, such as the capacity modulation. This study features the design of a novel capacity modulation reciprocating compressor, i.e., two-step capacity modulation (TCM). In a TCM compressor, capacity modulation is achieved by changing the dead volume in the cylinder. Instead of a concentric sleeve, an eccentric sleeve is used to change the dead volume for the clockwise and counterclockwise rotation of a motor. For stable capacity modulation, a new latching system with a key, a spring, and an eccentric sleeve is introduced, and the mode change reliability is verified by dynamic analysis

Dismissing Attachment Characteristics Dynamically Modulate Brain Networks Subserving Social Aversion

NARCIS (Netherlands)

Krause, Anna Linda; Borchardt, Viola; Li, Meng; van Tol, Marie-Jose; Demenescu, Liliana Ramona; Strauss, Bernhard; Kirchmanny, Helmut; Buchheim, Anna; Metzger, Coraline D.; Nolte, Tobias; Walter, Martin

2016-01-01

Attachment patterns influence actions, thoughts and feeling through a person's "inner working model". Speech charged with attachment-dependent content was proposed to modulate the activation of cognitive-emotional schemata in listeners. We performed a 7 Tesla rest-task-rest functional magnetic

Distal loop flexibility of a regulatory domain modulates dynamics and activity of C-terminal SRC kinase (csk.

Directory of Open Access Journals (Sweden)

Sulyman Barkho

Full Text Available The Src family of tyrosine kinases (SFKs regulate numerous aspects of cell growth and differentiation and are under the principal control of the C-terminal Src Kinase (Csk. Csk and SFKs share a modular design with the kinase domain downstream of the N-terminal SH2 and SH3 domains that regulate catalytic function and membrane localization. While the function of interfacial segments in these multidomain kinases are well-investigated, little is known about how surface sites and long-range, allosteric coupling control protein dynamics and catalytic function. The SH2 domain of Csk is an essential component for the down-regulation of all SFKs. A unique feature of the SH2 domain of Csk is the tight turn in place of the canonical CD loop in a surface site far removed from kinase domain interactions. In this study, we used a combination of experimental and computational methods to probe the importance of this difference by constructing a Csk variant with a longer SH2 CD loop to mimic the flexibility found in homologous kinase SH2 domains. Our results indicate that while the fold and function of the isolated domain and the full-length kinase are not affected by loop elongation, native protein dynamics that are essential for efficient catalysis are perturbed. We also identify key motifs and routes through which the distal SH2 site might influence catalysis at the active site. This study underscores the sensitivity of intramolecular signaling and catalysis to native protein dynamics that arise from modest changes in allosteric regions while providing a potential strategy to alter intrinsic activity and signaling modulation.

Quasi-Steady-State Analysis based on Structural Modules and Timed Petri Net Predict System’s Dynamics: The Life Cycle of the Insulin Receptor

Directory of Open Access Journals (Sweden)

Jennifer Scheidel

2015-12-01

Full Text Available The insulin-dependent activation and recycling of the insulin receptor play an essential role in the regulation of the energy metabolism, leading to a special interest for pharmaceutical applications. Thus, the recycling of the insulin receptor has been intensively investigated, experimentally as well as theoretically. We developed a time-resolved, discrete model to describe stochastic dynamics and study the approximation of non-linear dynamics in the context of timed Petri nets. Additionally, using a graph-theoretical approach, we analyzed the structure of the regulatory system and demonstrated the close interrelation of structural network properties with the kinetic behavior. The transition invariants decomposed the model into overlapping subnetworks of various sizes, which represent basic functional modules. Moreover, we computed the quasi-steady states of these subnetworks and demonstrated that they are fundamental to understand the dynamic behavior of the system. The Petri net approach confirms the experimental results of insulin-stimulated degradation of the insulin receptor, which represents a common feature of insulin-resistant, hyperinsulinaemic states.

Switching current imbalance mitigation in power modules with parallel connected SiC MOSFETs

DEFF Research Database (Denmark)

Beczkowski, Szymon; Jørgensen, Asger Bjørn; Li, Helong

2017-01-01

Multichip power modules use parallel connected chips to achieve high current rating. Due to a finite flexibility in a DBC layout, some electrical asymmetries will occur in the module. Parallel connected transistors will exhibit uneven static and dynamic current sharing due to these asymmetries....... Especially important are the couplings between gate and power loops of individual transistors. Fast changing source currents cause gate voltage imbalances yielding uneven switching currents. Equalizing gate voltages seen by paralleled transistors, done by adjusting source bond wires, is proposed...... in this paper. Analysis is performed on an industry standard DBC layout using numerically extracted module parasitics. The method of tuning individual source inductances shows clear improvement in dynamic current balancing and prevents excessive current overshoot during transistors turn-on....

Frequency shift and hysteresis suppression in contact-mode AFM using contact stiffness modulation

Directory of Open Access Journals (Sweden)

Belhaq M.

2012-07-01

Full Text Available In this paper the frequency response shift and hysteresis suppression of contact-mode atomic force microscopy is investigated using parametric modulation of the contact stiffness. Based on the Hertzian contact theory, a lumped single degree of freedom oscillator is considered for modeling the cantilever dynamics contact-mode atomic force microscopy. We use the technique of direct partition of motion and the method of multiple scales to obtain, respectively, the slow dynamic and the corresponding slow flow of the system. As results, this study shows that the amplitude of the contact stiffness modulation has a significant effect on the frequency response. Specifically, increasing the amplitude of the stiffness modulation suppresses hysteresis, decreases the peak amplitude and produces shifts towards higher and lower frequencies.

The Ovary of Tubifex tubifex (Clitellata, Naididae, Tubificinae Is Composed of One, Huge Germ-Line Cyst that Is Enriched with Cytoskeletal Components.

Directory of Open Access Journals (Sweden)

Anna Z Urbisz

Full Text Available Recent studies on the ovary organization and oogenesis in Tubificinae have revealed that their ovaries are small polarized structures that are composed of germ cells in subsequent stages of oogenesis that are associated with somatic cells. In syncytial cysts, as a rule, each germ cell is connected to the central cytoplasmic mass, the cytophore, via only one stable intercellular bridge (ring canal. In this paper we present detailed data about the composition of germ-line cysts in Tubifex tubifex with special emphasis on the occurrence and distribution of the cytoskeletal elements. Using fixed material and live cell imaging techniques, we found that the entire ovary of T. tubifex is composed of only one, huge multicellular germ-line cyst, which may contain up to 2,600 cells. Its architecture is broadly similar to the cysts that are found in other clitellate annelids, i.e. a common, anuclear cytoplasmic mass in the center of the cyst and germ cells that are connected to it via intercellular bridges. The cytophore in the T. tubifex cyst extends along the long axis of the ovary in the form of elongated and branched cytoplasmic strands. Rhodamine-coupled phalloidin staining revealed that the prominent strands of actin filaments occur inside the cytophore. Similar to the cytophore, F-actin strands are branched and they are especially well developed in the middle and outermost parts of the ovary. Microfilaments are also present in the ring canals that connect the germ cells with the cytophore in the narrow end of the ovary. Using TubulinTracker, we found that the microtubules form a prominent network of loosely and evenly distributed tubules inside the cytophore as well as in every germ cell. The well-developed cytoskeletal elements in T. tubifex ovary seem to ensure the integrity of such a huge germ-line cyst of complex (germ cells-ring canals-cytophore organization. A comparison between the cysts that are described here and other well-known female

A novel modulation scheme for noise reduction in analog fiber optic links

NARCIS (Netherlands)

Marpaung, D.A.I.; Roeloffzen, C.G.H.; van Etten, Wim; Megret, P.; Wuilpart, M.; Bette, S.; Staquet, N.

2005-01-01

A novel balanced modulation and detection scheme for analog fiber optic links is proposed to overcome the limitations in signal-to-noise ratio (SNR) and dynamic range (DR).In this scheme, the modulating signal is split into positive and negative halves and applied to a pair of laser diodes. Both

Network-dependent modulation of brain activity during sleep.

Science.gov (United States)

Watanabe, Takamitsu; Kan, Shigeyuki; Koike, Takahiko; Misaki, Masaya; Konishi, Seiki; Miyauchi, Satoru; Miyahsita, Yasushi; Masuda, Naoki

2014-09-01

Brain activity dynamically changes even during sleep. A line of neuroimaging studies has reported changes in functional connectivity and regional activity across different sleep stages such as slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. However, it remains unclear whether and how the large-scale network activity of human brains changes within a given sleep stage. Here, we investigated modulation of network activity within sleep stages by applying the pairwise maximum entropy model to brain activity obtained by functional magnetic resonance imaging from sleeping healthy subjects. We found that the brain activity of individual brain regions and functional interactions between pairs of regions significantly increased in the default-mode network during SWS and decreased during REM sleep. In contrast, the network activity of the fronto-parietal and sensory-motor networks showed the opposite pattern. Furthermore, in the three networks, the amount of the activity changes throughout REM sleep was negatively correlated with that throughout SWS. The present findings suggest that the brain activity is dynamically modulated even in a sleep stage and that the pattern of modulation depends on the type of the large-scale brain networks. Copyright © 2014 Elsevier Inc. All rights reserved.

A High Performance Delta-Sigma Modulator for Neurosensing.

Science.gov (United States)

Xu, Jian; Zhao, Menglian; Wu, Xiaobo; Islam, Md Kafiul; Yang, Zhi

2015-08-07

Recorded neural data are frequently corrupted by large amplitude artifacts that are triggered by a variety of sources, such as subject movements, organ motions, electromagnetic interferences and discharges at the electrode surface. To prevent the system from saturating and the electronics from malfunctioning due to these large artifacts, a wide dynamic range for data acquisition is demanded, which is quite challenging to achieve and would require excessive circuit area and power for implementation. In this paper, we present a high performance Delta-Sigma modulator along with several design techniques and enabling blocks to reduce circuit area and power. The modulator was fabricated in a 0.18-µm CMOS process. Powered by a 1.0-V supply, the chip can achieve an 85-dB peak signal-to-noise-and-distortion ratio (SNDR) and an 87-dB dynamic range when integrated over a 10-kHz bandwidth. The total power consumption of the modulator is 13 µW, which corresponds to a figure-of-merit (FOM) of 45 fJ/conversion step. These competitive circuit specifications make this design a good candidate for building high precision neurosensors.

Study Modules for Calculus-Based General Physics. [Includes Modules 11-14: Collisions; Equilibrium of Rigid Bodies; Rotational Dynamics; and Fluid Mechanics].

Science.gov (United States)

Fuller, Robert G., Ed.; And Others

This is part of a series of 42 Calculus Based Physics (CBP) modules totaling about 1,000 pages. The modules include study guides, practice tests, and mastery tests for a full-year individualized course in calculus-based physics based on the Personalized System of Instruction (PSI). The units are not intended to be used without outside materials;…

Observation of resonant symmetry lifting by an effective bias field in a parametrically modulated atomic trap

International Nuclear Information System (INIS)

Kim, Yonghee; Heo, Myoung-Sun; Moon, Geol; Kim, Ji-Hyoun; Jhe, Wonho; Noh, Heung-Ryoul

2010-01-01

We experimentally demonstrate resonant symmetry lifting in a parametrically modulated magneto-optical trap of cold 85 Rb atoms. This is achieved by applying a weak additional modulation at half the frequency of the strong parametric modulation, which acts as an effective static bias field to the system. We measure the system response by varying the amplitude of the additional fictitious bias as well as the relative phase between the bias and the parametric drive, and the results are in good agreement with theory. The additional modulation provides an additional degree of freedom to control the system, which is useful for investigating system properties such as susceptibility, dynamic response, and related critical phenomena. We also have measured the amplitude of the response to higher harmonics of the additional modulation frequency, which allows more precise understanding of the system dynamics.

A cytoskeletal activator and inhibitor are downstream targets of the frizzled/starry night planar cell polarity pathway in the Drosophila epidermis.

Science.gov (United States)

Adler, Paul N

2018-04-10

The frizzled pathway regulates the planar polarity of epithelial cells. In insects this is manifested by the polarity of cuticular structures such as hairs (trichomes) and sensory bristles. A variety of evidence has established that this is achieved by regulating the subcellular location for activating the cytoskeleton in the epithelial cells. How this is accomplished is still poorly understood. In the best-studied tissue, the Drosophila pupal wing two important cytoskeletal regulators have been identified. One, shavenoid (sha), appears to be an activator while the second multiple wing hairs (mwh), appears to be an inhibitor. In vitro biochemistry has confirmed that the Multiple Wing Hairs protein inhibits the elongation of F-actin chains and surprisingly that it also bundles F-actin. These two activities can explain the multifaceted mwh mutant phenotype. Copyright © 2018. Published by Elsevier Ltd.

Drinfeld currents of dynamical elliptic algebra

International Nuclear Information System (INIS)

Hou Boyu; Fan Heng; Yang Wenli; Cao Junpeng

2000-01-01

From the generalized Yang-Baxter relations RLL=LLR*, where R and R* are the dynamical R-matrix of A n-1 (1) type face model with the elliptic module shifted by the center of the algebra, using the Ding-Frenkel correspondence, the authors obtain the Drinfeld currents of dynamical elliptic algebra

Development of training modules for magnetic particle inspection

Science.gov (United States)

Kosaka, Daigo; Eisenmann, David J.; Enyart, Darrel; Nakagawa, Norio; Lo, Chester; Orman, David

2015-03-01

Magnetic particle inspection (MPI) is a nondestructive evaluation technique used with ferromagnetic materials. Although the application of this method may appear straightforward, MPI combines the complicated nature of electromagnetics, metallurgical material effects, fluid-particle motion dynamics, and physiological human factors into a single inspection. To fully appreciate industry specifications such as ASTM E-1444, users should develop a basic understanding of the many factors that are involved in MPI. We have developed a series of MPI training modules that are aimed at addressing this requirement. The modules not only offer qualitative explanations, but also show quantitative explanations in terms of measurement and numerical simulation data in many instances. There are five modules in all. Module ♯1 shows characteristics of waveforms and magnetizing methods. This allows MPI practitioners to make optimum choice of waveform and magnetizing method. Module ♯2 explains how material properties relate to the magnetic characteristics. Module ♯3 shows the strength of the excitation field or the flux leakage from a crack and how it compares to the detectability of a crack by MPI. Module ♯4 shows how specimen status may influence defect detection. Module ♯5 shows the effects of particle properties on defect detection.

Modulating weak interactions for molecular recognition: a dynamic combinatorial analysis for assessing the contribution of electrostatics to the stability of CH-π bonds in water.

Science.gov (United States)

Jiménez-Moreno, Ester; Gómez, Ana M; Bastida, Agatha; Corzana, Francisco; Jiménez-Oses, Gonzalo; Jiménez-Barbero, Jesús; Asensio, Juan Luis

2015-03-27

Electrostatic and charge-transfer contributions to CH-π complexes can be modulated by attaching electron-withdrawing substituents to the carbon atom. While clearly stabilizing in the gas phase, the outcome of this chemical modification in water is more difficult to predict. Herein we provide a definitive and quantitative answer to this question employing a simple strategy based on dynamic combinatorial chemistry. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Texture analysis on the fluence map to evaluate the degree of modulation for volumetric modulated arc therapy

International Nuclear Information System (INIS)

Park, So-Yeon; Kim, Il Han; Ye, Sung-Joon; Carlson, Joel

2014-01-01

Purpose: Texture analysis on fluence maps was performed to evaluate the degree of modulation for volumetric modulated arc therapy (VMAT) plans. Methods: A total of six textural features including angular second moment, inverse difference moment, contrast, variance, correlation, and entropy were calculated for fluence maps generated from 20 prostate and 20 head and neck VMAT plans. For each of the textural features, particular displacement distances (d) of 1, 5, and 10 were adopted. To investigate the deliverability of each VMAT plan, gamma passing rates of pretreatment quality assurance, and differences in modulating parameters such as multileaf collimator (MLC) positions, gantry angles, and monitor units at each control point between VMAT plans and dynamic log files registered by the Linac control system during delivery were acquired. Furthermore, differences between the original VMAT plan and the plan reconstructed from the dynamic log files were also investigated. To test the performance of the textural features as indicators for the modulation degree of VMAT plans, Spearman’s rank correlation coefficients (r s ) with the plan deliverability were calculated. For comparison purposes, conventional modulation indices for VMAT including the modulation complexity score for VMAT, leaf travel modulation complexity score, and modulation index supporting station parameter optimized radiation therapy (MI SPORT ) were calculated, and their correlations were analyzed in the same way. Results: There was no particular textural feature which always showed superior correlations with every type of plan deliverability. Considering the results comprehensively, contrast (d = 1) and variance (d = 1) generally showed considerable correlations with every type of plan deliverability. These textural features always showed higher correlations to the plan deliverability than did the conventional modulation indices, except in the case of modulating parameter differences. The r s values

Differential proteomics study of platelets in asymptomatic constitutional macrothrombocytopenia: altered levels of cytoskeletal proteins.

Science.gov (United States)

Karmakar, Shilpita; Saha, Sutapa; Banerjee, Debasis; Chakrabarti, Abhijit

2015-01-01

Harris platelet syndrome (HPS), also known as asymptomatic constitutional macrothrombocytopenia (ACMT), is an autosomal dominant platelet disorder characterized by mild-to-severe thrombocytopenia and giant platelets with normal platelet aggregation and absence of bleeding symptoms. We have attempted a comparative proteomics study for profiling of platelet proteins in healthy vs. pathological states to discover characteristic protein expression changes in macrothrombocytes and decipher the factors responsible for the functionally active yet morphologically distinct platelets. We have used 2-D gel-based protein separation techniques coupled with MALDI-ToF/ToF-based mass spectrometric identification and characterization of the proteins to investigate the differential proteome profiling of platelet proteins isolated from the peripheral blood samples of patients and normal volunteers. Our study revealed altered levels of actin-binding proteins such as myosin light chain, coactosin-like protein, actin-related protein 2/3 complex, and transgelin2 that hint toward the cytoskeletal changes necessary to maintain the structural and functional integrity of macrothrombocytes. We have also observed over expressed levels of peroxiredoxin2 that signifies the prevailing oxidative stress in these cells. Additionally, altered levels of protein disulfide isomerase and transthyretin provide insights into the measures adapted by the macrothrombocytes to maintain their normal functional activity. This first proteomics study of platelets from ACMT may provide an understanding of the structural stability and normal functioning of these platelets in spite of their large size. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sensor potency of the moonlighting enzyme-decorated cytoskeleton: the cytoskeleton as a metabolic sensor

Science.gov (United States)

2013-01-01

Background There is extensive evidence for the interaction of metabolic enzymes with the eukaryotic cytoskeleton. The significance of these interactions is far from clear. Presentation of the hypothesis In the cytoskeletal integrative sensor hypothesis presented here, the cytoskeleton senses and integrates the general metabolic activity of the cell. This activity depends on the binding to the cytoskeleton of enzymes and, depending on the nature of the enzyme, this binding may occur if the enzyme is either active or inactive but not both. This enzyme-binding is further proposed to stabilize microtubules and microfilaments and to alter rates of GTP and ATP hydrolysis and their levels. Testing the hypothesis Evidence consistent with the cytoskeletal integrative sensor hypothesis is presented in the case of glycolysis. Several testable predictions are made. There should be a relationship between post-translational modifications of tubulin and of actin and their interaction with metabolic enzymes. Different conditions of cytoskeletal dynamics and enzyme-cytoskeleton binding should reveal significant differences in local and perhaps global levels and ratios of ATP and GTP. The different functions of moonlighting enzymes should depend on cytoskeletal binding. Implications of the hypothesis The physical and chemical effects arising from metabolic sensing by the cytoskeleton would have major consequences on cell shape, dynamics and cell cycle progression. The hypothesis provides a framework that helps the significance of the enzyme-decorated cytoskeleton be determined. PMID:23398642

Preliminary studies of the dynamic stiffness modules of soil samples from the Solvay Sodium Plant waste landfill in Krakow

Directory of Open Access Journals (Sweden)

Pilecka Elżbieta

2017-01-01

Full Text Available The article presents the results of laboratory tests for determining the dynamic modules of the elasticity M and the shear G, for soil samples from the landfill of the closed Solvay Sodium Plant in Krakow. The tests were performed using a triaxial apparatus equipped with “bender” piezoelements. The samples subjected to these tests were taken from two boreholes, located in the area known as the “white seas”, whose formation is the result of Solvay Plant activity throughout the 20th century. The location of the test holes was planned at the place in which a road known as the “Łagiewnicka route” was planned. Studies on soil stiffness were also conducted as part of the one of the dissertation from 2008 to 2010 in the Cracow University of Technology. The results of these tests and the results of the laboratory tests that are presented in the article will be used in the designing of a computer model. This model is intended to help in assessing the dynamic impact of motor vehicle traffic on the planned Łagiewnicka route on the structure of the existing buildings located in the former Solvay Plant.

Simulation of Missing Pellet Surface thermal behavior with 3D dynamic gap element

International Nuclear Information System (INIS)

Kim, Hyo Chan; Yang, Yong Sik; Koo, Yang Hyun; Kang, Chang Hak; Lee Sung Uk; Yang, Dong Yol

2014-01-01

Most of the fuel performance codes that are able to simulate a multidimensional analysis are used to calculate the radial temperature distribution and perform a multidimensional mechanical analysis based on a one-dimensional (1D) temperature result. The FRAPCON-FRAPTRAN code system incorporates a 1D thermal module and two-dimensional (2D) mechanical module when FEM option is activated. In this method, the multidimensional gap conductance model is not required because one-dimensional thermal analysis is carried out. On the other hand, a gap conductance model for a multi-dimension should be developed in the code to perform a multidimensional thermal analysis. ALCYONE developed by CEA introduces an equivalent heat convection coefficient that represents the multidimensional gap conductance. However, the code does not employ dynamic gap conductance which is a function of gap thickness and gap characteristics in direct. The BISON code, which has been developed by INL (Idaho National Laboratory), employed a thermo-mechanical contact method that is specifically designed for tightly-coupled implicit solutions that employ Jacobian-free solution methods. Owing to tightly-coupled implicit solutions, the BISON code solves gap conductance and gap thickness simultaneously with given boundary conditions. In this paper, 3D dynamic gap element has been proposed to resolve convergence issue and nonlinear characteristic of multidimensional gap conductance. To evaluate 3D dynamic gap element module, 3D thermomechanical module using FORTRAN77 has been implemented incorporating 3D dynamic gap element. To demonstrate effect of 3D dynamic gap element, thermal behavior of missing pellet surface (MPS) has been simulated by the developed module. LWR fuel performance codes should incorporate thermo-mechanical loop to solve gap conductance problem, iteratively. However, gap conductance in multidimensional model is difficult issue owing to its nonlinearity and convergence characteristics. In

Ultra-compact plasmonic waveguide modulators

DEFF Research Database (Denmark)

Babicheva, Viktoriia

of developing new material platforms for integrated plasmonic devices. Furthermore, novel plasmonic materials such as transparent conductive oxides and transition metal nitrides can offer a variety of new opportunities. In particular, they offer adjustable/tailorable and nonlinear optical properties, dynamic...... modulators based on ultra-compact waveguides with different active cores. Plasmonic modulators with the active core such as indium phosphides or ferroelectrics sandwiched between metal plates have promising characteristics. Apart from the speed and dimensions advantages, the metal plates can serve...... as electrodes for electrical pumping of the active material making it easier to integrate. Including an additional layer in the plasmonic waveguide, in particular an ultrathin transparent conductive oxide film, allows the control of the dispersive properties of the waveguide and thus the higher efficiency...

Notch-RBP-J signaling regulates the mobilization and function of endothelial progenitor cells by dynamic modulation of CXCR4 expression in mice.

Directory of Open Access Journals (Sweden)

Lin Wang

Full Text Available Bone marrow (BM-derived endothelial progenitor cells (EPC have therapeutic potentials in promoting tissue regeneration, but how these cells are modulated in vivo has been elusive. Here, we report that RBP-J, the critical transcription factor mediating Notch signaling, modulates EPC through CXCR4. In a mouse partial hepatectomy (PHx model, RBP-J deficient EPC showed attenuated capacities of homing and facilitating liver regeneration. In resting mice, the conditional deletion of RBP-J led to a decrease of BM EPC, with a concomitant increase of EPC in the peripheral blood. This was accompanied by a down-regulation of CXCR4 on EPC in BM, although CXCR4 expression on EPC in the circulation was up-regulated in the absence of RBP-J. PHx in RBP-J deficient mice induced stronger EPC mobilization. In vitro, RBP-J deficient EPC showed lowered capacities of adhering, migrating, and forming vessel-like structures in three-dimensional cultures. Over-expression of CXCR4 could at least rescue the defects in vessel formation by the RBP-J deficient EPC. These data suggested that the RBP-J-mediated Notch signaling regulated EPC mobilization and function, at least partially through dynamic modulation of CXCR4 expression. Our findings not only provide new insights into the regulation of EPC, but also have implications for clinical therapies using EPC in diseases.

Design of an ultra low power third order continuous time current mode ΣΔ modulator for WLAN applications.

Science.gov (United States)

Behzadi, Kobra; Baghelani, Masoud

2014-05-01

This paper presents a third order continuous time current mode ΣΔ modulator for WLAN 802.11b standard applications. The proposed circuit utilized feedback architecture with scaled and optimized DAC coefficients. At circuit level, we propose a modified cascade current mirror integrator with reduced input impedance which results in more bandwidth and linearity and hence improves the dynamic range. Also, a very fast and precise novel dynamic latch based current comparator is introduced with low power consumption. This ultra fast comparator facilitates increasing the sampling rate toward GHz frequencies. The modulator exhibits dynamic range of more than 60 dB for 20 MHz signal bandwidth and OSR of 10 while consuming only 914 μW from 1.8 V power supply. The FoM of the modulator is calculated from two different methods, and excellent performance is achieved for proposed modulator.

Oestradiol and progesterone differentially alter cytoskeletal protein expression and flame cell morphology in Taenia crassiceps.

Science.gov (United States)

Ambrosio, Javier R; Ostoa-Saloma, Pedro; Palacios-Arreola, M Isabel; Ruíz-Rosado, Azucena; Sánchez-Orellana, Pedro L; Reynoso-Ducoing, Olivia; Nava-Castro, Karen E; Martínez-Velázquez, Nancy; Escobedo, Galileo; Ibarra-Coronado, Elizabeth G; Valverde-Islas, Laura; Morales-Montor, Jorge

2014-09-01

We examined the effects of oestradiol (E2) and progesterone (P4) on cytoskeletal protein expression in the helminth Taenia crassiceps - specifically actin, tubulin and myosin. These proteins assemble into flame cells, which constitute the parasite excretory system. Total protein extracts were obtained from E2- and P4-treated T. crassiceps cysticerci and untreated controls, and analysed by one- and two-dimensional protein electrophoresis, flow cytometry, immunofluorescence and videomicroscopy. Exposure of T. crassiceps cysticerci to E2 and P4 induced differential protein expression patterns compared with untreated controls. Changes in actin, tubulin and myosin expression were confirmed by flow cytometry of parasite cells and immunofluorescence. In addition, parasite morphology was altered in response to E2 and P4 versus controls. Flame cells were primarily affected at the level of the ciliary tuft, in association with the changes in actin, tubulin and myosin. We conclude that oestradiol and progesterone act directly on T. crassiceps cysticerci, altering actin, tubulin and myosin expression and thus affecting the assembly and function of flame cells. Our results increase our understanding of several aspects of the molecular crosstalk between host and parasite, which might be useful in designing anthelmintic drugs that exclusively impair parasitic proteins which mediate cell signaling and pathogenic reproduction and establishment. Copyright © 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Nonlinear dynamic effects in a two-wave CO2 laser

International Nuclear Information System (INIS)

Gorobets, V A; Kozlov, K V; Kuntsevich, B F; Petukhov, V O

1999-01-01

Theoretical and experimental investigations were made of nonlinear dynamic regimes of the operation of a two-wave CO 2 laser with cw excitation in an electric discharge and loss modulation in one of the channels. Nonlinear amplitude - frequency characteristics of each of the laser channels have two low-frequency resonance spikes, associated with forced linear oscillations of two coupled oscillators, and high-frequency spikes, corresponding to doubling of the period of the output radiation oscillations. At low loss-modulation frequencies the intensity oscillations of the output radiation in the coupled channels are in antiphase, whereas at high modulation frequencies the dynamics is cophasal. Nonlinear dynamic effects, such as doubling of the period and of the repetition frequency of the pulses and chaotic oscillations of the output radiation intensity, are observed for certain system parameters. (control of laser radiation parameters)

MARCKS-related protein regulates cytoskeletal organization at cell-cell and cell-substrate contacts in epithelial cells.

Science.gov (United States)

Van Itallie, Christina M; Tietgens, Amber Jean; Aponte, Angel; Gucek, Marjan; Cartagena-Rivera, Alexander X; Chadwick, Richard S; Anderson, James M

2018-02-02

Treatment of epithelial cells with interferon-γ and TNF-α (IFN/TNF) results in increased paracellular permeability. To identify relevant proteins mediating barrier disruption, we performed proximity-dependent biotinylation (BioID) of occludin and found that tagging of MARCKS-related protein (MRP; also known as MARCKSL1) increased ∼20-fold following IFN/TNF administration. GFP-MRP was focused at the lateral cell membrane and its overexpression potentiated the physiological response of the tight junction barrier to cytokines. However, deletion of MRP did not abrogate the cytokine responses, suggesting that MRP is not required in the occludin-dependent IFN/TNF response. Instead, our results reveal a key role for MRP in epithelial cells in control of multiple actin-based structures, likely by regulation of integrin signaling. Changes in focal adhesion organization and basal actin stress fibers in MRP-knockout (KO) cells were reminiscent of those seen in FAK-KO cells. In addition, we found alterations in cell-cell interactions in MRP-KO cells associated with increased junctional tension, suggesting that MRP may play a role in focal adhesion-adherens junction cross talk. Together, our results are consistent with a key role for MRP in cytoskeletal organization of cell contacts in epithelial cells. © 2018. Published by The Company of Biologists Ltd.

APL/JHU free flight tests of the General Purpose Heat Source module. Testing: 5-7 March 1984

International Nuclear Information System (INIS)

Baker, W.M. II.

1984-01-01

Purpose of the test was to obtain statistical information on the dynamics of the General Purpose Heat Source (GPHS) module at terminal speeds. Models were designed to aerodynamically and dynamically represent the GPHS module. Normal and high speed photographic coverage documented the motion of the models. This report documents test parameters and techniques for the free-spin tests. It does not include data analysis

4-(1-Ethyl-4-anisyl-imidazol-5-yl)-N-hydroxycinnamide – A new pleiotropic HDAC inhibitor targeting cancer cell signalling and cytoskeletal organisation

Energy Technology Data Exchange (ETDEWEB)

Mahal, Katharina, E-mail: katharina.mahal@uni-bayreuth.de [Organic Chemistry Laboratory, University of Bayreuth, Universitätsstrasse 30, 95440 Bayreuth (Germany); Kahlen, Philip, E-mail: philip.kahlen@uni-bayreuth.de [Department of Genetics, University of Bayreuth, Universitätsstrasse 30, 95440 Bayreuth (Germany); Biersack, Bernhard, E-mail: bernhard.biersack@yahoo.com [Organic Chemistry Laboratory, University of Bayreuth, Universitätsstrasse 30, 95440 Bayreuth (Germany); Schobert, Rainer, E-mail: rainer.schobert@uni-bayreuth.de [Organic Chemistry Laboratory, University of Bayreuth, Universitätsstrasse 30, 95440 Bayreuth (Germany)

2015-08-15

Histone deacetylases (HDAC) which play a crucial role in cancer cell proliferation are promising drug targets. However, HDAC inhibitors (HDACi) modelled on natural hydroxamic acids such as trichostatin A frequently lead to resistance or even an increased agressiveness of tumours. As a workaround we developed 4-(1-ethyl-4-anisyl-imidazol-5-yl)-N-hydroxycinnamide (etacrox), a hydroxamic acid that combines HDAC inhibition with synergistic effects of the 4,5-diarylimidazole residue. Etacrox proved highly cytotoxic against a panel of metastatic and resistant cancer cell lines while showing greater specificity for cancer over non-malignant cells when compared to the approved HDACi vorinostat. Like the latter, etacrox and the closely related imidazoles bimacroxam and animacroxam acted as pan-HDACi yet showed some specificity for HDAC6. Akt signalling and interference with nuclear beta-catenin localisation were elicited by etacrox at lower concentrations when compared to vorinostat. Moreover, etacrox disrupted the microtubule and focal adhesion dynamics of cancer cells and inhibited the proteolytic activity of prometastatic and proangiogenic matrix metalloproteinases. As a consequence, etacrox acted strongly antimigratory and antiinvasive against various cancer cell lines in three-dimensional transwell invasion assays and also antiangiogenic in vivo with respect to blood vessel formation in the chorioallantoic membrane assay. These pleiotropic effects and its water-solubility and tolerance by mice render etacrox a promising new HDACi candidate. - Graphical abstract: A novel histone deacetylase inhibitor with pleiotropic anticancer effects. - Highlights: • Etacrox is a new HDACi with cytotoxic, antiangiogenic and antiinvasive activity. • Etacrox causes aberrant cancer cell signalling and cytoskeletal reorganisation. • Pro-metastatic and angiogenic matrix metalloproteinases are inhibited by etacrox. • Etacrox impairs blood vessel maturation in vivo and cancer cell

4-(1-Ethyl-4-anisyl-imidazol-5-yl)-N-hydroxycinnamide – A new pleiotropic HDAC inhibitor targeting cancer cell signalling and cytoskeletal organisation

International Nuclear Information System (INIS)

Mahal, Katharina; Kahlen, Philip; Biersack, Bernhard; Schobert, Rainer

2015-01-01

Histone deacetylases (HDAC) which play a crucial role in cancer cell proliferation are promising drug targets. However, HDAC inhibitors (HDACi) modelled on natural hydroxamic acids such as trichostatin A frequently lead to resistance or even an increased agressiveness of tumours. As a workaround we developed 4-(1-ethyl-4-anisyl-imidazol-5-yl)-N-hydroxycinnamide (etacrox), a hydroxamic acid that combines HDAC inhibition with synergistic effects of the 4,5-diarylimidazole residue. Etacrox proved highly cytotoxic against a panel of metastatic and resistant cancer cell lines while showing greater specificity for cancer over non-malignant cells when compared to the approved HDACi vorinostat. Like the latter, etacrox and the closely related imidazoles bimacroxam and animacroxam acted as pan-HDACi yet showed some specificity for HDAC6. Akt signalling and interference with nuclear beta-catenin localisation were elicited by etacrox at lower concentrations when compared to vorinostat. Moreover, etacrox disrupted the microtubule and focal adhesion dynamics of cancer cells and inhibited the proteolytic activity of prometastatic and proangiogenic matrix metalloproteinases. As a consequence, etacrox acted strongly antimigratory and antiinvasive against various cancer cell lines in three-dimensional transwell invasion assays and also antiangiogenic in vivo with respect to blood vessel formation in the chorioallantoic membrane assay. These pleiotropic effects and its water-solubility and tolerance by mice render etacrox a promising new HDACi candidate. - Graphical abstract: A novel histone deacetylase inhibitor with pleiotropic anticancer effects. - Highlights: • Etacrox is a new HDACi with cytotoxic, antiangiogenic and antiinvasive activity. • Etacrox causes aberrant cancer cell signalling and cytoskeletal reorganisation. • Pro-metastatic and angiogenic matrix metalloproteinases are inhibited by etacrox. • Etacrox impairs blood vessel maturation in vivo and cancer cell

Statistical modeling of nitrogen-dependent modulation of root system architecture in Arabidopsis thaliana.

Science.gov (United States)

Araya, Takao; Kubo, Takuya; von Wirén, Nicolaus; Takahashi, Hideki

2016-03-01

Plant root development is strongly affected by nutrient availability. Despite the importance of structure and function of roots in nutrient acquisition, statistical modeling approaches to evaluate dynamic and temporal modulations of root system architecture in response to nutrient availability have remained as widely open and exploratory areas in root biology. In this study, we developed a statistical modeling approach to investigate modulations of root system architecture in response to nitrogen availability. Mathematical models were designed for quantitative assessment of root growth and root branching phenotypes and their dynamic relationships based on hierarchical configuration of primary and lateral roots formulating the fishbone-shaped root system architecture in Arabidopsis thaliana. Time-series datasets reporting dynamic changes in root developmental traits on different nitrate or ammonium concentrations were generated for statistical analyses. Regression analyses unraveled key parameters associated with: (i) inhibition of primary root growth under nitrogen limitation or on ammonium; (ii) rapid progression of lateral root emergence in response to ammonium; and (iii) inhibition of lateral root elongation in the presence of excess nitrate or ammonium. This study provides a statistical framework for interpreting dynamic modulation of root system architecture, supported by meta-analysis of datasets displaying morphological responses of roots to diverse nitrogen supplies. © 2015 Institute of Botany, Chinese Academy of Sciences.

Dynamic method for the measurement of Young'S modulus. Application to nuclear graphites; Methode de mesure dynamique du module d'Young. Application aux graphites nucleaires

Energy Technology Data Exchange (ETDEWEB)

Pattou, F; Trutt, J C

1963-07-01

A dynamic method has been developed for measuring Young's modulus and the rigidity modulus using the 'Forster Elastomat'. The principle consists in the determination of the resonance frequencies of graphite samples submitted to transverse, longitudinal, and torsional vibrations. The first two modes of vibration make it possible to calculate the elasticity modulus or the Young's modulus E, the third mode makes possible the calculation of the rigidity modulus G. The relationships from which the moduli E and G are measured are given. A systematic study has been made of graphite samples produced by extrusion or compression and submitted afterwards to one or several impregnations with pitch. For graphites made from the same coke by the same method, a linear relationship has been found for Young's modulus as a function of the apparent density. For the same apparent density, graphites made from different starting materials have generally different Young's moduli that bear a relationship to the crystalline characteristics of the material. The measurements of the rigidity modulus C made on different graphites also show the influence of crystallite orientation. (authors) [French] Une methode de mesure dynamique du module d'Young et du module de rigidite du graphite utilisant 'l'Elastomat Forster' a ete mise au point. Le principe consiste a determiner les frequences de resonance d'echantillons de graphite soumis a des vibrations transversales, longitudinales et de torsion. Les deux premiers modes de vibration permettent de calculer le module d'elasticite ou module d'Young E, le troisieme mode de vibration permet de calculer le module de rigidite G. Apres avoir decrit la methode de mesure, on rappelle les relations qui permettent de calculer les modules E et G. L'etude systematique d'echantillons de graphite, fabriques par filage ou pressage et ayant subi eventuellement une ou plusieurs impregnations au brai a ete effectuee. Pour les graphites issus du meme coke et fabriques

Mitochondrial Dynamics in Cardiovascular Health and Disease

OpenAIRE

Ong, Sang-Bing; Hall, Andrew R.; Hausenloy, Derek J.

2013-01-01

Significance: Mitochondria are dynamic organelles capable of changing their shape and distribution by undergoing either fission or fusion. Changes in mitochondrial dynamics, which is under the control of specific mitochondrial fission and fusion proteins, have been implicated in cell division, embryonic development, apoptosis, autophagy, and metabolism. Although the machinery for modulating mitochondrial dynamics is present in the cardiovascular system, its function there has only recently be...

Delivery of modulated electron beams with conventional photon multi-leaf collimators

International Nuclear Information System (INIS)

Klein, Eric E; Mamalui-Hunter, Maria; Low, Daniel A

2009-01-01

Electron beam radiotherapy is an accepted method to treat shallow tumors. However, modulation of electrons to customize dose distributions has not readily been achieved. Studies of bolus and tertiary collimation systems have been met with limitations. We pursue the use of photon multi-leaf collimators (MLC) for modulated electron radiotherapy (MERT) to achieve customized distributions for potential clinical use. As commercial planning systems do not support the use of MLC with electrons, planning was conducted using Monte Carlo calculations. Segmented and dynamic modulated delivery of multiple electron segments was configured, calculated and delivered for validation. Delivery of electrons with segmented or dynamic leaf motion was conducted. A phantom possessing an idealized stepped target was planned and optimized with subsequent validation by measurements. Finally, clinical treatment plans were conducted for post-mastectomy and cutaneous lymphoma of the scalp using forward optimization techniques. Comparison of calculations and measurements was successful with agreement of ±2%/2 mm for the energies, segment sizes, depths tested for delivered segments for the dynamic and segmented delivery. Clinical treatment plans performed provided optimal dose coverage of the target while sparing distal organs at risk. Execution of plans using an anthropomorphic phantom to ensure safe and efficient delivery was conducted. Our study validates that MERT is not only possible using the photon MLC, but the efficient and safe delivery inherent with the dynamic delivery provides an ideal technique for shallow tumor treatment.

Exploring the Possible Role of Lysine Acetylation on Entamoeba histolytica Virulence: A Focus on the Dynamics of the Actin Cytoskeleton

Directory of Open Access Journals (Sweden)

L. López-Contreras

2013-01-01

Full Text Available Cytoskeleton remodeling can be regulated, among other mechanisms, by lysine acetylation. The role of acetylation on cytoskeletal and other proteins of Entamoeba histolytica has been poorly studied. Dynamic rearrangements of the actin cytoskeleton are crucial for amebic motility and capping formation, processes that may be effective means of evading the host immune response. Here we report the possible effect of acetylation on the actin cytoskeleton dynamics and in vivo virulence of E. histolytica. Using western blot, immunoprecipitation, microscopy assays, and in silico analysis, we show results that strongly suggest that the increase in Aspirin-induced cytoplasm proteins acetylation reduced cell movement and capping formation, likely as a consequence of alterations in the structuration of the actin cytoskeleton. Additionally, intrahepatic inoculation of Aspirin-treated trophozoites in hamsters resulted in severe impairment of the amebic virulence. Taken together, these results suggest an important role for lysine acetylation in amebic invasiveness and virulence.

Microsoft Dynamics CRM 2011 cookbook

CERN Document Server

Bhattacharya, Dipankar

2013-01-01

This is a Cookbook with recipes aimed at all levels with lots of practical walkthroughs for virtualization techniques.This book is great for Dynamics CRM 2011 professionals who have a beginner level understanding of the system and are looking to get a good grounding in how to deploy, maintain, configure, and customize a Dynamics CRM 2011 application efficiently. It's assumed that the reader has a basic level understanding of IT infrastructure topologies along with functional knowledge of Dynamics CRM 2011 Sales, Marketing, and Services modules.

The dynamics of integrate-and-fire: mean versus variance modulations and dependence on baseline parameters.

Science.gov (United States)

Pressley, Joanna; Troyer, Todd W

2011-05-01

The leaky integrate-and-fire (LIF) is the simplest neuron model that captures the essential properties of neuronal signaling. Yet common intuitions are inadequate to explain basic properties of LIF responses to sinusoidal modulations of the input. Here we examine responses to low and moderate frequency modulations of both the mean and variance of the input current and quantify how these responses depend on baseline parameters. Across parameters, responses to modulations in the mean current are low pass, approaching zero in the limit of high frequencies. For very low baseline firing rates, the response cutoff frequency matches that expected from membrane integration. However, the cutoff shows a rapid, supralinear increase with firing rate, with a steeper increase in the case of lower noise. For modulations of the input variance, the gain at high frequency remains finite. Here, we show that the low-frequency responses depend strongly on baseline parameters and derive an analytic condition specifying the parameters at which responses switch from being dominated by low versus high frequencies. Additionally, we show that the resonant responses for variance modulations have properties not expected for common oscillatory resonances: they peak at frequencies higher than the baseline firing rate and persist when oscillatory spiking is disrupted by high noise. Finally, the responses to mean and variance modulations are shown to have a complementary dependence on baseline parameters at higher frequencies, resulting in responses to modulations of Poisson input rates that are independent of baseline input statistics.

Digital Modulation Identification Model Using Wavelet Transform and Statistical Parameters

Directory of Open Access Journals (Sweden)

P. Prakasam

2008-01-01

Full Text Available A generalized modulation identification scheme is developed and presented. With the help of this scheme, the automatic modulation classification and recognition of wireless communication signals with a priori unknown parameters are possible effectively. The special features of the procedure are the possibility to adapt it dynamically to nearly all modulation types, and the capability to identify. The developed scheme based on wavelet transform and statistical parameters has been used to identify M-ary PSK, M-ary QAM, GMSK, and M-ary FSK modulations. The simulated results show that the correct modulation identification is possible to a lower bound of 5 dB. The identification percentage has been analyzed based on the confusion matrix. When SNR is above 5 dB, the probability of detection of the proposed system is more than 0.968. The performance of the proposed scheme has been compared with existing methods and found it will identify all digital modulation schemes with low SNR.

Texture analysis on the fluence map to evaluate the degree of modulation for volumetric modulated arc therapy

Energy Technology Data Exchange (ETDEWEB)

Park, So-Yeon [Department of Radiation Oncology, Seoul National University Hospital, Seoul 110-744 (Korea, Republic of); Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul 110-744 (Korea, Republic of); Biomedical Research Institute, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Interdisciplinary Program in Radiation Applied Life Science, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Kim, Il Han [Department of Radiation Oncology, Seoul National University Hospital, Seoul 110-744 (Korea, Republic of); Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul 110-744 (Korea, Republic of); Biomedical Research Institute, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Department of Radiation Oncology, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Ye, Sung-Joon [Department of Radiation Oncology, Seoul National University Hospital, Seoul 110-744, (Korea, Republic of); Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul 110-744 (Korea, Republic of); Biomedical Research Institute, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Program in Biomedical Radiation Sciences, Department of Transdisciplinary Studies, Seoul National University Graduate School of Convergence Science and Technology, Suwon 433-270 (Korea, Republic of); Carlson, Joel [Biomedical Research Institute, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Program in Biomedical Radiation Sciences, Department of Transdisciplinary Studies, Seoul National University Graduate School of Convergence Science and Technology, Suwon 433-270 (Korea, Republic of); and others

2014-11-01

Purpose: Texture analysis on fluence maps was performed to evaluate the degree of modulation for volumetric modulated arc therapy (VMAT) plans. Methods: A total of six textural features including angular second moment, inverse difference moment, contrast, variance, correlation, and entropy were calculated for fluence maps generated from 20 prostate and 20 head and neck VMAT plans. For each of the textural features, particular displacement distances (d) of 1, 5, and 10 were adopted. To investigate the deliverability of each VMAT plan, gamma passing rates of pretreatment quality assurance, and differences in modulating parameters such as multileaf collimator (MLC) positions, gantry angles, and monitor units at each control point between VMAT plans and dynamic log files registered by the Linac control system during delivery were acquired. Furthermore, differences between the original VMAT plan and the plan reconstructed from the dynamic log files were also investigated. To test the performance of the textural features as indicators for the modulation degree of VMAT plans, Spearman’s rank correlation coefficients (r{sub s}) with the plan deliverability were calculated. For comparison purposes, conventional modulation indices for VMAT including the modulation complexity score for VMAT, leaf travel modulation complexity score, and modulation index supporting station parameter optimized radiation therapy (MI{sub SPORT}) were calculated, and their correlations were analyzed in the same way. Results: There was no particular textural feature which always showed superior correlations with every type of plan deliverability. Considering the results comprehensively, contrast (d = 1) and variance (d = 1) generally showed considerable correlations with every type of plan deliverability. These textural features always showed higher correlations to the plan deliverability than did the conventional modulation indices, except in the case of modulating parameter differences. The r

Effects of a modulated vortex structure on the diffraction dynamics of ring Airy Gaussian beams.

Science.gov (United States)

Huang, Xianwei; Shi, Xiaohui; Deng, Zhixiang; Bai, Yanfeng; Fu, Xiquan

2017-09-01

The evolution of the ring Airy Gaussian beams with a modulated vortex in free space is numerically investigated. Compared with the unmodulated vortex, the unique property is that the beam spots first break up, and then gather. The evolution of the beams is influenced by the parameters of the vortex modulation, and the splitting phenomenon gets enhanced with multiple rings becoming light spots if the modulation depth increases. The symmetric branch pattern of the beam spots gets changed when the number of phase folds increases, and the initial modulation phase only impacts the angle of the beam spots. Moreover, a large distribution factor correlates to a hollow Gaussian vortex shape and weakens the splitting and gathering trend. By changing the initial parameters of the vortex modulation and the distribution factor, the peak intensity is greatly affected. In addition, the energy flow and the angular momentum are elucidated with the beam evolution features being confirmed.

Dynamical decoherence control of multi-partite systems

International Nuclear Information System (INIS)

Gordon, Goren

2009-01-01

A unified theory is given of dynamically modified decay and decoherence of field-driven multipartite systems. When this universal framework is applied to two-level systems or qubits experiencing either amplitude or phase noise due to their coupling to a thermal bath, it results in completely analogous formulae for the modified decoherence rates in both cases. The spectral representation of the modified decoherence rates underscores the main insight derived from this approach, namely, that the decoherence rate is the spectral overlap of the noise and modulation spectra. This allows us to come up with general recipes for modulation schemes for the optimal reduction of decoherence under realistic constraints. An extension of the treatment to multilevel and multipartite systems exploits intra-system symmetries to dynamically protect multipartite entangled states. Another corollary of this treatment is that entanglement, which is very susceptible to noise and can die, i.e., vanish at finite times, can be resuscitated by appropriate modulations prescribed by our universal formalism. This dynamical decoherence control is also shown to be advantageous in quantum computation setups, where control fields are applied concurrently with the gate operations to increase the gate fidelity. (phd tutorial)

Speech recognition from spectral dynamics

Indian Academy of Sciences (India)

Carrier nature of speech; modulation spectrum; spectral dynamics ... the relationships between phonetic values of sounds and their short-term spectral envelopes .... the number of free parameters that need to be estimated from training data.

Temperature Modulation with Specified Detection Point on Metal Oxide Semiconductor Gas Sensors for E-Nose Application

Directory of Open Access Journals (Sweden)

Arief SUDARMAJI

2015-03-01

Full Text Available Temperature modulation technique, some called dynamic measurement mode, on Metal-Oxide Semiconductor (MOS/MOX gas sensor has been widely observed and employed in many fields. We present its development, a Specified Detection Point (SDP on modulated sensing element of MOS sensor is applied which associated to its temperature modulation, temperature modulation-SDP so-named. We configured the rectangular modulation signal for MOS gas sensors (TGSs and FISs using PSOC CY8C28445-24PVXI (Programmable System on Chip which also functioned as acquisition unit and interface to a computer. Initial responses and selectivity evaluations were performed using statistical tool and Principal Component Analysis (PCA to differ sample gases (Toluene, Ethanol and Ammonia on dynamic chamber measurement under various frequencies (0.25 Hz, 1 Hz, 4 Hz and duty-cycles (25 %, 50 %, 75 %. We found that at lower frequency the response waveform of the sensors becomes more sloping and distinct, and selected modulations successfully increased the selectivity either on singular or array sensors rather than static temperature measurement.

Modulation of the Conformational Dynamics of Apo-Adenylate Kinase through a π-Cation Interaction.

Science.gov (United States)

Halder, Ritaban; Manna, Rabindra Nath; Chakraborty, Sandipan; Jana, Biman

2017-06-15

Large-scale conformational transition from open to closed state of adenylate kinase (ADK) is essential for its catalytic cycle. Apo-ADK undergoes conformational transition in a way that closely resembles an open-to-closed conformational transition. Here, equilibrium simulations, free-energy simulations, and quantum mechanics/molecular mechanics (QM/MM) calculations in combination with several bioinformatics approaches have been used to explore the molecular origin of this conformational transition in apo-ADK. In addition to its conventional open state, Escherichia coli apo-ADK adopts conformations that resemble a closed-like intermediate, the "half-open-half-closed" (HOHC) state, and a π-cation interaction can account for the stability of this HOHC state. Energetics and the electronic properties of this π-cation interaction have been explored using QM/MM calculations. Upon rescinding the π-cation interaction, the conformational landscape of the apo-ADK changes completely. The apo-ADK population is shifted completely toward the open state. This π-cation interaction is highly conserved in bacterial ADK; the cationic guanidinium moiety of a conserved ARG interacts with the delocalized π-electron cloud of either PHE or TYR. Interestingly, this study demonstrates the modulation of a principal protein dynamics by a conserved specific π-cation interaction across different organisms.

Head position modulates optokinetic nystagmus.

Science.gov (United States)

Pettorossi, V E; Ferraresi, A; Botti, F M; Panichi, R; Barmack, N H

2011-08-01

Orientation and movement relies on both visual and vestibular information mapped in separate coordinate systems. Here, we examine how coordinate systems interact to guide eye movements of rabbits. We exposed rabbits to continuous horizontal optokinetic stimulation (HOKS) at 5°/s to evoke horizontal eye movements, while they were statically or dynamically roll-tilted about the longitudinal axis. During monocular or binocular HOKS, when the rabbit was roll-tilted 30° onto the side of the eye stimulated in the posterior → anterior (P → A) direction, slow phase eye velocity (SPEV) increased by 3.5-5°/s. When the rabbit was roll-tilted 30° onto the side of the eye stimulated in the A → P direction, SPEV decreased to ~2.5°/s. We also tested the effect of roll-tilt after prolonged optokinetic stimulation had induced a negative optokinetic afternystagmus (OKAN II). In this condition, the SPEV occurred in the dark, "open loop." Modulation of SPEV of OKAN II depended on the direction of the nystagmus and was consistent with that observed during "closed loop" HOKS. Dynamic roll-tilt influenced SPEV evoked by HOKS in a similar way. The amplitude and the phase of SPEV depended on the frequency of vestibular oscillation and on HOKS velocity. We conclude that the change in the linear acceleration of the gravity vector with respect to the head during roll-tilt modulates the gain of SPEV depending on its direction. This modulation improves gaze stability at different image retinal slip velocities caused by head roll-tilt during centric or eccentric head movement.

Temperature-insensitive fiber Bragg grating dynamic pressure sensing system.

Science.gov (United States)

Guo, Tuan; Zhao, Qida; Zhang, Hao; Zhang, Chunshu; Huang, Guiling; Xue, Lifang; Dong, Xiaoyi

2006-08-01

Temperature-insensitive dynamic pressure measurement using a single fiber Bragg grating (FBG) based on reflection spectrum bandwidth modulation and optical power detection is proposed. A specifically designed double-hole cantilever beam is used to provide a pressure-induced axial strain gradient along the sensing FBG and is also used to modulate the reflection bandwidth of the grating. The bandwidth modulation is immune to spatially uniform temperature effects, and the pressure can be unambiguously determined by measuring the reflected optical power, avoiding the complex wavelength interrogation system. The system acquisition time is up to 85 Hz for dynamic pressure measurement, and the thermal fluctuation is kept less than 1.2% full-scale for a temperature range of -10 degrees C to 80 degrees C.

Differential nuclear shape dynamics of invasive andnon-invasive breast cancer cells are associated with actin cytoskeleton organization and stability.

Science.gov (United States)

Chiotaki, Rena; Polioudaki, Hara; Theodoropoulos, Panayiotis A

2014-08-01

Cancer cells often exhibit characteristic aberrations in their nuclear architecture, which are indicative of their malignant potential. In this study, we have examined the nuclear and cytoskeletal composition, attachment configuration dynamics, and osmotic or drug treatment response of invasive (Hs578T and MDA-MB-231) and non-invasive (MCF-10A and MCF-7) breast cancer cell lines. Unlike MCF-10A and MCF-7, Hs578T and MDA-MB-231 cells showed extensive nuclear elasticity and deformability and displayed distinct kinetic profiles during substrate attachment. The nuclear shape of MCF-10A and MCF-7 cells remained almost unaffected upon detachment, hyperosmotic shock, or cytoskeleton depolymerization, while Hs578T and MDA-MB-231 revealed dramatic nuclear contour malformations following actin reorganization.

Module theory, extending modules and generalizations

CERN Document Server

Tercan, Adnan

2016-01-01

The main focus of this monograph is to offer a comprehensive presentation of known and new results on various generalizations of CS-modules and CS-rings. Extending (or CS) modules are generalizations of injective (and also semisimple or uniform) modules. While the theory of CS-modules is well documented in monographs and textbooks, results on generalized forms of the CS property as well as dual notions are far less present in the literature. With their work the authors provide a solid background to module theory, accessible to anyone familiar with basic abstract algebra. The focus of the book is on direct sums of CS-modules and classes of modules related to CS-modules, such as relative (injective) ejective modules, (quasi) continuous modules, and lifting modules. In particular, matrix CS-rings are studied and clear proofs of fundamental decomposition results on CS-modules over commutative domains are given, thus complementing existing monographs in this area. Open problems round out the work and establish the...

Dynamic circadian modulation in a biomathematical model for the effects of sleep and sleep loss on waking neurobehavioral performance.

Science.gov (United States)

McCauley, Peter; Kalachev, Leonid V; Mollicone, Daniel J; Banks, Siobhan; Dinges, David F; Van Dongen, Hans P A

2013-12-01

Recent experimental observations and theoretical advances have indicated that the homeostatic equilibrium for sleep/wake regulation--and thereby sensitivity to neurobehavioral impairment from sleep loss--is modulated by prior sleep/wake history. This phenomenon was predicted by a biomathematical model developed to explain changes in neurobehavioral performance across days in laboratory studies of total sleep deprivation and sustained sleep restriction. The present paper focuses on the dynamics of neurobehavioral performance within days in this biomathematical model of fatigue. Without increasing the number of model parameters, the model was updated by incorporating time-dependence in the amplitude of the circadian modulation of performance. The updated model was calibrated using a large dataset from three laboratory experiments on psychomotor vigilance test (PVT) performance, under conditions of sleep loss and circadian misalignment; and validated using another large dataset from three different laboratory experiments. The time-dependence of circadian amplitude resulted in improved goodness-of-fit in night shift schedules, nap sleep scenarios, and recovery from prior sleep loss. The updated model predicts that the homeostatic equilibrium for sleep/wake regulation--and thus sensitivity to sleep loss--depends not only on the duration but also on the circadian timing of prior sleep. This novel theoretical insight has important implications for predicting operator alertness during work schedules involving circadian misalignment such as night shift work.

The Drosophila HEM-2/NAP1 homolog KETTE controls axonal pathfinding and cytoskeletal organization.

Science.gov (United States)

Hummel, T; Leifker, K; Klämbt, C

2000-04-01

In Drosophila, the correct formation of the segmental commissures depends on neuron-glial interactions at the midline. The VUM midline neurons extend axons along which glial cells migrate in between anterior and posterior commissures. Here, we show that the gene kette is required for the normal projection of the VUM axons and subsequently disrupts glial migration. Axonal projection defects are also found for many other moto- and interneurons. In addition, kette affects the cell morphology of mesodermal and epidermal derivatives, which show an abnormal actin cytoskeleton. The KETTE protein is homologous to the transmembrane protein HEM-2/NAP1 evolutionary conserved from worms to vertebrates. In vitro analysis has shown a specific interaction of the vertebrate HEM-2/NAP1 with the SH2-SH3 adapter protein NCK and the small GTPase RAC1, which both have been implicated in regulating cytoskeleton organization and axonal growth. Hypomorphic kette mutations lead to axonal defects similar to mutations in the Drosophila NCK homolog dreadlocks. Furthermore, we show that kette and dock mutants genetically interact. NCK is thought to interact with the small G proteins RAC1 and CDC42, which play a role in axonal growth. In line with these observations, a kette phenocopy can be obtained following directed expression of mutant DCDC42 or DRAC1 in the CNS midline. In addition, the kette mutant phenotype can be partially rescued by expression of an activated DRAC1 transgene. Our data suggest an important role of the HEM-2 protein in cytoskeletal organization during axonal pathfinding.

Nonlinear PDEs a dynamical systems approach

CERN Document Server

Schneider, Guido

2017-01-01

This is an introductory textbook about nonlinear dynamics of PDEs, with a focus on problems over unbounded domains and modulation equations. The presentation is example-oriented, and new mathematical tools are developed step by step, giving insight into some important classes of nonlinear PDEs and nonlinear dynamics phenomena which may occur in PDEs. The book consists of four parts. Parts I and II are introductions to finite- and infinite-dimensional dynamics defined by ODEs and by PDEs over bounded domains, respectively, including the basics of bifurcation and attractor theory. Part III introduces PDEs on the real line, including the Korteweg-de Vries equation, the Nonlinear Schrödinger equation and the Ginzburg-Landau equation. These examples often occur as simplest possible models, namely as amplitude or modulation equations, for some real world phenomena such as nonlinear waves and pattern formation. Part IV explores in more detail the connections between such complicated physical systems and the reduced...

Catenins

DEFF Research Database (Denmark)

Perez-Moreno, Mirna; Fuchs, Elaine

2006-01-01

intercellular communication between different cell types within a tissue. These findings reveal novel aspects of AJ function in normal tissues and offer insights into how changes in AJs and their associated proteins and cytoskeletal dynamics impact wound-repair and cancer......., conventional views have similarly been shaken about the other two major AJ catenins, alpha-catenin and p120-catenin. Catenins have emerged as molecular sensors that integrate cell-cell junctions and cytoskeletal dynamics with signaling pathways that govern morphogenesis, tissue homeostasis, and even......Adherens junctions have been traditionally viewed as building blocks of tissue architecture. The foundations for this view began to change with the discovery that a central component of AJs, beta-catenin, can also function as a transcriptional cofactor in Wnt signaling. In recent years...

Signaling mechanisms of neurite outgrowth induced by the cell adhesion molecules NCAM and N-cadherin

DEFF Research Database (Denmark)

Hansen, S M; Berezin, V; Bock, E

2008-01-01

Formation of appropriate neural circuits depends on a complex interplay between extracellular guiding cues and intracellular signaling events that result in alterations of cytoskeletal dynamics and a neurite growth response. Surface-expressed cell adhesion molecules (CAMs) interact with the surro......Formation of appropriate neural circuits depends on a complex interplay between extracellular guiding cues and intracellular signaling events that result in alterations of cytoskeletal dynamics and a neurite growth response. Surface-expressed cell adhesion molecules (CAMs) interact...... extracellular guidance cues to intracellular events and thereby regulating neurite outgrowth. In this review, we focus on two CAMs, the neural cell adhesion molecule (NCAM) and N-cadherin, and their ability to mediate signaling associated with a neurite outgrowth response. In particular, we will focus on direct...

Analogue demonstration of a high temperature superconducting sigma-delta modulator with 27 GHz sampling

Energy Technology Data Exchange (ETDEWEB)

Forrester, M.G.; Hunt, B.D.; Miller, D.L.; Talvacchio, J.; Young, R.M. [Northrop Grumman Science and Technology Center, Pittsburgh, PA 15235-5098 (United States)

1999-11-01

We have successfully fabricated and tested a high temperature superconducting (HTS) sigma-delta modulator for analogue-to-digital conversion. This is the first demonstration of a GHz sampling A-to-D in HTS. The 15-junction single-flux-quantum (SFQ) circuit, fabricated using an epitaxial multilayer HTS process with YBCO/Co-YBCO/YBCO edge junctions, was internally clocked at 27 GHz and used to convert a 5.01 MHz signal. The modulator demonstrated a spur-free dynamic range of more than 75 dB. Two-tone measurements with 5.01 MHz and 5.51 MHz signals demonstrated third-order intermodulation products to be lower than -59 dBc. Demonstration of a functional HTS modulator represents a significant milestone in the development of high dynamic range ADCs suitable for such applications as surveillance radar. (author)

Chemical reactions in the presence of surface modulation and stirring

OpenAIRE

Kamhawi, Khalid; Náraigh, Lennon Ó

2009-01-01

We study the dynamics of simple reactions where the chemical species are confined on a general, time-modulated surface, and subjected to externally-imposed stirring. The study of these inhomogeneous effects requires a model based on a reaction-advection-diffusion equation, which we derive. We use homogenization methods to show that up to second order in a small scaling parameter, the modulation effects on the concentration field are asymptotically equivalent for systems with or without stirri...

Improved stability and performance from sigma-delta modulators using 1-bit vector quantization

DEFF Research Database (Denmark)

Risbo, Lars

1993-01-01

A novel class of sigma-delta modulators is presented. The usual scalar 1-b quantizer in a sigma-delta modulator is replaced by a 1-b vector quantizer with a N-dimensional input state-vector from the linear feedback filter. Generally, the vector quantizer changes the nonlinear dynamics...... of the modulator, and a proper choice of vector quantizer can improve both system stability and coding performance. It is shown how to construct the vector quantizer in order to limit the excursions in state-space. The proposed method is demonstrated graphically for a simple second-order modulator...

Dynamic aperture and transverse proton diffusion in HERA

International Nuclear Information System (INIS)

Zimmermann, F.

1994-04-01

The dynamic aperture caused by persistent-current nonlinear field errors is an important concern in the design of superconducting hadron storage rings. The HERA proton ring is the second superconducting accelerator in operation. In this lecture note, its measured dynamic aperture is compared with that inferred from comprehensive trackig studies. To understand the difference between prediction and measurement, a semi-analytical method is developed for evaluating transverse diffusion rates due to various processes, such as modulational diffusion or sweeping diffusion this analysis makes use of parameters for high-order resonances in the transverse phase space, which are obtained by normal-form algorithms using differential-algebra software. This semi-analytical results are consistent wit the measurements, and suggest that the actual dynamic aperture is caused by an interplay of tune modulation and nonlinear magnetic fields

Pulse-amplitude modulation of optical injection-locked quantum-dot lasers

Science.gov (United States)

Zhou, Yue-Guang; Wang, Cheng

2018-02-01

This work theoretically investigates the four-level pulse-amplitude modulation characteristics of quantum dot lasers subject to optical injection. The rate equation model takes into account carrier dynamics in the carrier reservoir, in the excited state, and in the ground state, as well as photon dynamics and phase dynamics of the electric field. It is found that the optical injection significantly improves the eye diagram quality through suppressing the relaxation oscillation, while the extinction ratio is reduced as well. In addition, both the adiabatic chirp and the transient chirp of the signal are substantially suppressed.

Nonlinear dynamics of non-equilibrium holes in p-type modulation-doped GaInNAs/GaAs quantum wells

Directory of Open Access Journals (Sweden)

Amann Andreas

2011-01-01

Full Text Available Abstract Nonlinear charge transport parallel to the layers of p-modulation-doped GaInNAs/GaAs quantum wells (QWs is studied both theoretically and experimentally. Experimental results show that at low temperature, T = 13 K, the presence of an applied electric field of about 6 kV/cm leads to the heating of the high mobility holes in the GaInNAs QWs, and their real-space transfer (RST into the low-mobility GaAs barriers. This results in a negative differential mobility and self-generated oscillatory instabilities in the RST regime. We developed an analytical model based upon the coupled nonlinear dynamics of the real-space hole transfer and of the interface potential barrier controlled by space-charge in the doped GaAs layer. Our simulation results predict dc bias-dependent self-generated current oscillations with frequencies in the high microwave range.

Field control of anisotropic spin transport and spin helix dynamics in a modulation-doped GaAs quantum well

Science.gov (United States)

Anghel, S.; Passmann, F.; Singh, A.; Ruppert, C.; Poshakinskiy, A. V.; Tarasenko, S. A.; Moore, J. N.; Yusa, G.; Mano, T.; Noda, T.; Li, X.; Bristow, A. D.; Betz, M.

2018-03-01

Electron spin transport and dynamics are investigated in a single, high-mobility, modulation-doped, GaAs quantum well using ultrafast two-color Kerr-rotation microspectroscopy, supported by qualitative kinetic theory simulations of spin diffusion and transport. Evolution of the spins is governed by the Dresselhaus bulk and Rashba structural inversion asymmetries, which manifest as an effective magnetic field that can be extracted directly from the experimental coherent spin precession. A spin-precession length λSOI is defined as one complete precession in the effective magnetic field. It is observed that application of (i) an out-of-plane electric field changes the spin decay time and λSOI through the Rashba component of the spin-orbit coupling, (ii) an in-plane magnetic field allows for extraction of the Dresselhaus and Rashba parameters, and (iii) an in-plane electric field markedly modifies both the λSOI and diffusion coefficient.

Bistability of self-modulation oscillations in an autonomous solid-state ring laser

International Nuclear Information System (INIS)

Dudetskii, V Yu

2013-01-01

Bistable self-modulation regimes of generation for a ring YAG : Nd chip laser with the counterpropagating waves asymmetrically coupled via backward scattering are simulated numerically. Two branches of bistable self-modulation regimes of generation are found in the domain of the parametric resonance between the selfmodulation and relaxation oscillations. The self-modulation regimes observed in earlier experiments pertain to only one of the branches. Possible reasons for such a discrepancy are considered, related to the influence of technical and natural noise on the dynamics of solid-state ring lasers. (control of laser radiation parameters)

The cytoskeletal binding domain of band 3 is required for multiprotein complex formation and retention during erythropoiesis

Science.gov (United States)

Satchwell, Timothy J; Hawley, Bethan R; Bell, Amanda J; Ribeiro, M. Leticia; Toye, Ashley M

2015-01-01

Band 3 is the most abundant protein in the erythrocyte membrane and forms the core of a major multiprotein complex. The absence of band 3 in human erythrocytes has only been reported once, in the homozygous band 3 Coimbra patient. We used in vitro culture of erythroblasts derived from this patient, and separately short hairpin RNA-mediated depletion of band 3, to investigate the development of a band 3-deficient erythrocyte membrane and to specifically assess the stability and retention of band 3 dependent proteins in the absence of this core protein during terminal erythroid differentiation. Further, using lentiviral transduction of N-terminally green fluorescent protein-tagged band 3, we demonstrated the ability to restore expression of band 3 to normal levels and to rescue secondary deficiencies of key proteins including glycophorin A, protein 4.2, CD47 and Rh proteins arising from the absence of band 3 in this patient. By transducing band 3-deficient erythroblasts from this patient with band 3 mutants with absent or impaired ability to associate with the cytoskeleton we also demonstrated the importance of cytoskeletal connectivity for retention both of band 3 and of its associated dependent proteins within the reticulocyte membrane during the process of erythroblast enucleation. PMID:25344524

Heterogeneous Cytoskeletal Force Distribution Delineates the Onset Ca2+ Influx Under Fluid Shear Stress in Astrocytes

Directory of Open Access Journals (Sweden)

Mohammad M. Maneshi

2018-03-01

Full Text Available Mechanical perturbations increase intracellular Ca2+ in cells, but the coupling of mechanical forces to the Ca2+ influx is not well understood. We used a microfluidic chamber driven with a high-speed pressure servo to generate defined fluid shear stress to cultured astrocytes, and simultaneously measured cytoskeletal forces using a force sensitive actinin optical sensor and intracellular Ca2+. Fluid shear generated non-uniform forces in actinin that critically depended on the stimulus rise time emphasizing the presence of viscoelasticity in the activating sequence. A short (ms shear pulse with fast rise time (2 ms produced an immediate increase in actinin tension at the upstream end of the cell with minimal changes at the downstream end. The onset of Ca2+ rise began at highly strained areas. In contrast to stimulus steps, slow ramp stimuli produced uniform forces throughout the cells and only a small Ca2+ response. The heterogeneity of force distribution is exaggerated in cells having fewer stress fibers and lower pre-tension in actinin. Disruption of cytoskeleton with cytochalasin-D (Cyt-D eliminated force gradients, and in those cells Ca2+ elevation started from the soma. Thus, Ca2+ influx with a mechanical stimulus depends on local stress within the cell and that is time dependent due to viscoelastic mechanics.

Action Potential Modulation of Neural Spin Networks Suggests Possible Role of Spin

CERN Document Server

Hu, H P

2004-01-01

In this paper we show that nuclear spin networks in neural membranes are modulated by action potentials through J-coupling, dipolar coupling and chemical shielding tensors and perturbed by microscopically strong and fluctuating internal magnetic fields produced largely by paramagnetic oxygen. We suggest that these spin networks could be involved in brain functions since said modulation inputs information carried by the neural spike trains into them, said perturbation activates various dynamics within them and the combination of the two likely produce stochastic resonance thus synchronizing said dynamics to the neural firings. Although quantum coherence is desirable and may indeed exist, it is not required for these spin networks to serve as the subatomic components for the conventional neural networks.

Potent antiproliferative cembrenoids accumulate in tobacco upon infection with Rhodococcus fascians and trigger unusual microtubule dynamics in human glioblastoma cells.

Directory of Open Access Journals (Sweden)

Aminata P Nacoulma

Full Text Available AIMS: Though plant metabolic changes are known to occur during interactions with bacteria, these were rarely challenged for pharmacologically active compounds suitable for further drug development. Here, the occurrence of specific chemicals with antiproliferative activity against human cancer cell lines was evidenced in hyperplasia (leafy galls induced when plants interact with particular phytopathogens, such as the Actinomycete Rhodococcus fascians. METHODS: We examined leafy galls fraction F3.1.1 on cell proliferation, cell division and cytoskeletal disorganization of human cancer cell lines using time-lapse videomicroscopy imaging, combined with flow cytometry and immunofluorescence analysis. We determined the F3.1.1-fraction composition by gas chromatography coupled to mass spectrometry. RESULTS: The leafy galls induced on tobacco by R. fascians yielded fraction F3.1.1 which inhibited proliferation of glioblastoma U373 cells with an IC50 of 4.5 µg/mL, F.3.1.1 was shown to increase cell division duration, cause nuclear morphological deformations and cell enlargement, and, at higher concentrations, karyokinesis defects leading to polyploidization and apoptosis. F3.1.1 consisted of a mixture of isomers belonging to the cembrenoids. The cellular defects induced by F3.1.1 were caused by a peculiar cytoskeletal disorganization, with the occurrence of fragmented tubulin and strongly organized microtubule aggregates within the same cell. Colchicine, paclitaxel, and cembrene also affected U373 cell proliferation and karyokinesis, but the induced microtubule rearrangement was very different from that provoked by F3.1.1. Altogether our data indicate that the cembrenoid isomers in F3.1.1 have a unique mode of action and are able to simultaneously modulate microtubule polymerization and stability.

Potential-induced degradation of Cu(In,Ga)Se2 photovoltaic modules

Science.gov (United States)

Yamaguchi, Seira; Jonai, Sachiko; Hara, Kohjiro; Komaki, Hironori; Shimizu-Kamikawa, Yukiko; Shibata, Hajime; Niki, Shigeru; Kawakami, Yuji; Masuda, Atsushi

2015-08-01

Potential-induced degradation (PID) of Cu(In,Ga)Se2 (CIGS) photovoltaic (PV) modules fabricated from integrated submodules is investigated. PID tests were performed by applying a voltage of -1000 V to connected submodule interconnector ribbons at 85 °C. The normalized energy conversion efficiency of a standard module decreases to 0.2 after the PID test for 14 days. This reveals that CIGS modules suffer PID under this experimental condition. In contrast, a module with non-alkali glass shows no degradation, which implies that the degradation occurs owing to alkali metal ions, e.g., Na+, migrating from the cover glass. The results of dynamic secondary ion mass spectrometry show Na accumulation in the n-ZnO transparent conductive oxide layer of the degraded module. A CIGS PV module with an ionomer (IO) encapsulant instead of a copolymer of ethylene and vinyl acetate shows no degradation. This reveals that the IO encapsulant can prevent PID of CIGS modules. A degraded module can recover from its performance losses by applying +1000 V to connected submodule interconnector ribbons from an Al plate placed on the test module.

Spinoculation Triggers Dynamic Actin and Cofilin Activity That Facilitates HIV-1 Infection of Transformed and Resting CD4 T Cells▿

Science.gov (United States)

Guo, Jia; Wang, Weifeng; Yu, Dongyang; Wu, Yuntao

2011-01-01

Centrifugal inoculation, or spinoculation, is widely used in virology research to enhance viral infection. However, the mechanism remained obscure. Using HIV-1 infection of human T cells as a model, we demonstrate that spinoculation triggers dynamic actin and cofilin activity, probably resulting from cellular responses to centrifugal stress. This actin activity also leads to the upregulation of the HIV-1 receptor and coreceptor, CD4 and CXCR4, enhancing viral binding and entry. We also demonstrate that an actin inhibitor, jasplakinolide, diminishes spin-mediated enhancement. In addition, small interfering RNA (siRNA) knockdown of LIMK1, a cofilin kinase, decreases the enhancement. These results suggest that spin-mediated enhancement cannot be explained simply by a virus-concentrating effect; rather, it is coupled with spin-induced cytoskeletal dynamics that promote receptor mobilization, viral entry, and postentry processes. Our results highlight the importance of cofilin and a dynamic cytoskeleton for the initiation of viral infection. Our results also indicate that caution needs to be taken in data interpretation when cells are spinoculated; some of the spin-induced cellular permissiveness may be beyond the natural capacity of an infecting virus. PMID:21795326

How Dynamic Visualization Technology Can Support Molecular Reasoning

Science.gov (United States)

Levy, Dalit

2013-01-01

This paper reports the results of a study aimed at exploring the advantages of dynamic visualization for the development of better understanding of molecular processes. We designed a technology-enhanced curriculum module in which high school chemistry students conduct virtual experiments with dynamic molecular visualizations of solid, liquid, and…

Laser Noise and its Impact on the Performance of Intensity-Modulation with Direct-Detection Analog Photonic Links

National Research Council Canada - National Science Library

Urick, Vincent J; Devgan, Preetpaul S; McKinney, Jason D; Dexter, James L

2007-01-01

The equations for radio-frequency gain, radio-frequency noise figure, compression dynamic range and spurious-free dynamic range are derived for an analog photonic link employing intensity modulation and direct detection...

Simulating transient dynamics of the time-dependent time fractional Fokker–Planck systems

Energy Technology Data Exchange (ETDEWEB)

Kang, Yan-Mei, E-mail: ymkang@mail.xjtu.edu.cn

2016-09-16

For a physically realistic type of time-dependent time fractional Fokker–Planck (FP) equation, derived as the continuous limit of the continuous time random walk with time-modulated Boltzmann jumping weight, a semi-analytic iteration scheme based on the truncated (generalized) Fourier series is presented to simulate the resultant transient dynamics when the external time modulation is a piece-wise constant signal. At first, the iteration scheme is demonstrated with a simple time-dependent time fractional FP equation on finite interval with two absorbing boundaries, and then it is generalized to the more general time-dependent Smoluchowski-type time fractional Fokker–Planck equation. The numerical examples verify the efficiency and accuracy of the iteration method, and some novel dynamical phenomena including polarized motion orientations and periodic response death are discussed. - Highlights: • An iteration method is proposed for the transient dynamics of time-dependent time fractional Fokker–Planck equations. • The method is based on Fourier Series solution and the multi-step transition probability formula. • With the time-modulated subdiffusion on finite interval as example, the polarized motion orientation is disclosed. • With the time-modulated subdiffusion within a confined potential as example, the death of dynamic response is observed.

Simulating transient dynamics of the time-dependent time fractional Fokker–Planck systems

International Nuclear Information System (INIS)

Kang, Yan-Mei

2016-01-01

For a physically realistic type of time-dependent time fractional Fokker–Planck (FP) equation, derived as the continuous limit of the continuous time random walk with time-modulated Boltzmann jumping weight, a semi-analytic iteration scheme based on the truncated (generalized) Fourier series is presented to simulate the resultant transient dynamics when the external time modulation is a piece-wise constant signal. At first, the iteration scheme is demonstrated with a simple time-dependent time fractional FP equation on finite interval with two absorbing boundaries, and then it is generalized to the more general time-dependent Smoluchowski-type time fractional Fokker–Planck equation. The numerical examples verify the efficiency and accuracy of the iteration method, and some novel dynamical phenomena including polarized motion orientations and periodic response death are discussed. - Highlights: • An iteration method is proposed for the transient dynamics of time-dependent time fractional Fokker–Planck equations. • The method is based on Fourier Series solution and the multi-step transition probability formula. • With the time-modulated subdiffusion on finite interval as example, the polarized motion orientation is disclosed. • With the time-modulated subdiffusion within a confined potential as example, the death of dynamic response is observed.

Intensity-modulated stereotactic radiosurgery using dynamic micro-multileaf collimation

International Nuclear Information System (INIS)

Benedict, Stanley H.; Cardinale, Robert M.; Wu Qiuwen; Zwicker, Robert D.; Broaddus, William C.; Mohan, Radhe

2001-01-01

Purpose: The implementation of dynamic leaf motion on a micro-multileaf collimator system provides the capability for intensity-modulated stereotactic radiosurgery (IMSRS), and the consequent potential for improved dose distributions for irregularly shaped tumor volumes adjacent to critical organs. This study explores the use of IMSRS to provide improved tumor coverage and normal tissue sparing for small cranial tumors relative to plans based on multiple fixed uniform-intensity beams or traditional circular collimator arc-based stereotactic techniques. Methods and Materials: Four patient cases involving small brain lesions are presented and analyzed. The cases were chosen to include a representative selection of target shapes, number of targets, and adjacent critical areas. Patient plans generated for these comparisons include standard arcs with multiple circular collimators, and fixed noncoplanar static fields with uniform-intensity beams and IMSRS. Parameters used for evaluation of the plans include the percentage of irradiated volume to tumor volume (PITV), normal tissue dose-volume histograms, and dose-homogeneity ratios. All IMSRS plans were computed using previously established IMRT techniques adapted for use with the BrainLAB M3 micro-multileaf collimator. The algorithms comprising the IMRT system for optimization of intensity distributions and conversion into leaf trajectories of the BrainLab M3 were developed at our institution. The ADAC Pinnacle 3 radiation treatment-planning system was used for dose calculations and for input of contours for target volumes and normal critical structures. Results: For all cases, the IMSRS plans showed a high degree of conformity of the dose distribution with the target shape. The IMSRS plans provided either (1) a smaller volume of normal tissue irradiated to significant dose levels, generally taken as doses greater than 50% of the prescription, or (2) a lower dose to an important adjacent critical organ. The reduction in

[Results of statistical analysis of the dynamics of ionizing radiation dose fields in the service module of the International Space Station in 2000-2012].

Science.gov (United States)

Mitrikas, V G

2014-01-01

The on-going 24th solar cycle (SC) is distinguished from the previous ones by low activity. On the contrary, levels of proton fluxes from galactic cosmic rays (GCR) are high, which increases the proton flow striking the Earth's radiation belts (ERB). Therefore, at present the absorbed dose from ERB protons should be calculated with consideration of the tangible increase of protons intensity built into the model descriptions based on experimental measurements during the minimum between cycles 19 and 20, and the cycle 21 maximum. The absorbed dose from GCR and ERB protons copies galactic protons dynamics, while the ERB electrons dose copies SC dynamics. The major factors that determine the absorbed dose value are SC phase, ISS orbital altitude and shielding of the dosimeter readings of which are used in analysis. The paper presents the results of dynamic analysis of absorbed doses measured by a variety of dosimeters, namely, R-16 (2 ionization chambers), DB8-1, DB8-2, DB8-3, DB8-4 as a function of ISS orbit altitude and SC phase. The existence of annual variation in the absorbed dose dynamics has been confirmed; several additional variations with the periods of 17 and 52 months have been detected. Modulation of absorbed dose variations by the SC and GCR amplitudes has been demonstrated.

Irreducible Specht modules are signed Young modules

OpenAIRE

Hemmer, David J.

2005-01-01

Recently Donkin defined signed Young modules as a simultaneous generalization of Young and twisted Young modules for the symmetric group. We show that in odd characteristic, if a Specht module $S^\\lambda$ is irreducible, then $S^\\lambda$ is a signed Young module. Thus the set of irreducible Specht modules coincides with the set of irreducible signed Young modules. This provides evidence for our conjecture that the signed Young modules are precisely the class of indecomposable self-dual module...

Modulated structure calculated for superconducting hydrogen sulfide

Energy Technology Data Exchange (ETDEWEB)

Majumdar, Arnab; Tse, John S.; Yao, Yansun [Department of Physics and Engineering Physics, University of Saskatchewan, Saskatoon, SK (Canada)

2017-09-11

Compression of hydrogen sulfide using first principles metadynamics and molecular dynamics calculations revealed a modulated structure with high proton mobility which exhibits a diffraction pattern matching well with experiment. The structure consists of a sublattice of rectangular meandering SH{sup -} chains and molecular-like H{sub 3}S{sup +} stacked alternately in tetragonal and cubic slabs forming a long-period modulation. The novel structure offers a new perspective on the possible origin of the superconductivity at very high temperatures in which the conducting electrons in the SH chains are perturbed by the fluxional motions of the H{sub 3}S resulting in strong electron-phonon coupling. (copyright 2017 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

Differential Aging Trajectories of Modulation of Activation to Cognitive Challenge in APOE ε4 Groups: Reduced Modulation Predicts Poorer Cognitive Performance.

Science.gov (United States)

Foster, Chris M; Kennedy, Kristen M; Rodrigue, Karen M

2017-07-19

The present study was designed to investigate the effect of a genetic risk factor for Alzheimer's disease (AD), ApolipoproteinE ε4 (APOEε4), on the ability of the brain to modulate activation in response to cognitive challenge in a lifespan sample of healthy human adults. A community-based sample of 181 cognitively intact, healthy adults were recruited from the Dallas-Fort Worth metroplex. Thirty-one APOEε4+ individuals (48% women), derived from the parent sample, were matched based on sex, age, and years of education to 31 individuals who were APOEε4-negative (APOEε4-). Ages ranged from 20 to 86 years of age. Blood oxygen level-dependent functional magnetic resonance imaging was collected during the performance of a visuospatial distance judgment task with three parametric levels of difficulty. Multiple regression was used in a whole-brain analysis with age, APOE group, and their interaction predicting functional brain modulation in response to difficulty. Results revealed an interaction between age and APOE in a large cluster localized primarily to the bilateral precuneus. APOEε4- individuals exhibited age-invariant modulation in response to task difficulty, whereas APOEε4+ individuals showed age-related reduction of modulation in response to increasing task difficulty compared with ε4- individuals. Decreased modulation in response to cognitive challenge was associated with reduced task accuracy as well as poorer name-face associative memory performance. Findings suggest that APOEε4 is associated with a reduction in the ability of the brain to dynamically modulate in response to cognitive challenge. Coupled with a significant genetic risk factor for AD, changes in modulation may provide additional information toward identifying individuals potentially at risk for cognitive decline associated with preclinical AD. SIGNIFICANCE STATEMENT Understanding how risk factors for Alzheimer's disease (AD) affect brain function and cognition in healthy adult samples

High-speed Si/GeSi hetero-structure Electro Absorption Modulator.

Science.gov (United States)

Mastronardi, L; Banakar, M; Khokhar, A Z; Hattasan, N; Rutirawut, T; Bucio, T Domínguez; Grabska, K M; Littlejohns, C; Bazin, A; Mashanovich, G; Gardes, F Y

2018-03-19

The ever-increasing demand for integrated, low power interconnect systems is pushing the bandwidth density of CMOS photonic devices. Taking advantage of the strong Franz-Keldysh effect in the C and L communication bands, electro-absorption modulators in Ge and GeSi are setting a new standard in terms of device footprint and power consumption for next generation photonics interconnect arrays. In this paper, we present a compact, low power electro-absorption modulator (EAM) Si/GeSi hetero-structure based on an 800 nm SOI overlayer with a modulation bandwidth of 56 GHz. The device design and fabrication tolerant process are presented, followed by the measurement analysis. Eye diagram measurements show a dynamic ER of 5.2 dB at a data rate of 56 Gb/s at 1566 nm, and calculated modulator power is 44 fJ/bit.

Microarray analysis identifies a common set of cellular genes modulated by different HCV replicon clones

Directory of Open Access Journals (Sweden)

Gerosolimo Germano

2008-06-01

Full Text Available Abstract Background Hepatitis C virus (HCV RNA synthesis and protein expression affect cell homeostasis by modulation of gene expression. The impact of HCV replication on global cell transcription has not been fully evaluated. Thus, we analysed the expression profiles of different clones of human hepatoma-derived Huh-7 cells carrying a self-replicating HCV RNA which express all viral proteins (HCV replicon system. Results First, we compared the expression profile of HCV replicon clone 21-5 with both the Huh-7 parental cells and the 21-5 cured (21-5c cells. In these latter, the HCV RNA has been eliminated by IFN-α treatment. To confirm data, we also analyzed microarray results from both the 21-5 and two other HCV replicon clones, 22-6 and 21-7, compared to the Huh-7 cells. The study was carried out by using the Applied Biosystems (AB Human Genome Survey Microarray v1.0 which provides 31,700 probes that correspond to 27,868 human genes. Microarray analysis revealed a specific transcriptional program induced by HCV in replicon cells respect to both IFN-α-cured and Huh-7 cells. From the original datasets of differentially expressed genes, we selected by Venn diagrams a final list of 38 genes modulated by HCV in all clones. Most of the 38 genes have never been described before and showed high fold-change associated with significant p-value, strongly supporting data reliability. Classification of the 38 genes by Panther System identified functional categories that were significantly enriched in this gene set, such as histones and ribosomal proteins as well as extracellular matrix and intracellular protein traffic. The dataset also included new genes involved in lipid metabolism, extracellular matrix and cytoskeletal network, which may be critical for HCV replication and pathogenesis. Conclusion Our data provide a comprehensive analysis of alterations in gene expression induced by HCV replication and reveal modulation of new genes potentially useful

Domain wall propagation tuning in magnetic nanowires through geometric modulation

Energy Technology Data Exchange (ETDEWEB)

Arzuza, L.C.C., E-mail: luisarzuza179@gmail.com [Instituto de Física Gleb Wataghin, Universidade Estadual de Campinas, 13083-859 Campinas (SP) (Brazil); Universidad de la Costa, Departamento de Ciencias Naturales y Exactas, Calle 58 No. 55-66, Barranquilla (Colombia); López-Ruiz, R. [Instituto de Física Gleb Wataghin, Universidade Estadual de Campinas, 13083-859 Campinas (SP) (Brazil); Salazar-Aravena, D. [Instituto de Física Gleb Wataghin, Universidade Estadual de Campinas, 13083-859 Campinas (SP) (Brazil); Departamento de Física, Facultad de Ciencias, Universidad de Tarapacá, 1000007 Arica (Chile); Knobel, M. [Instituto de Física Gleb Wataghin, Universidade Estadual de Campinas, 13083-859 Campinas (SP) (Brazil); Brazilian Nanotechnology National Laboratory, Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), 13083-970 Campinas (SP) (Brazil); Béron, F.; Pirota, K.R. [Instituto de Física Gleb Wataghin, Universidade Estadual de Campinas, 13083-859 Campinas (SP) (Brazil)

2017-06-15

Highlights: • The modulated nanowires dynamics occurs through two reversal modes. • Modulated nanowires show a change in the χ in contrast to homogeneous ones. • The FORC method reveals a non-uniform stray field due to shape modulation. - Abstract: The magnetic behavior of nickel modulated nanowires embedded in porous alumina membranes is investigated. Their diameters exhibit a sharp transition between below (35 nm) and above (52 nm) the theoretical limit for transverse and vortex domain walls. Magnetic hysteresis loops and first-order reversal curves (FORCs) were measured on several ordered nanowire arrays with different wide-narrow segment lengths ratio and compared with those from homogenous nanowires. The experimental magnetic response evidences a rather complex susceptibility behavior for nanowires with modulated diameter. Micromagnetic simulations on isolated and first-neighbors arrays of nanowires show that the domain wall structure, which depends on the segment diameter, suffers a transformation while crossing the diameter modulation, but without any pinning. The experimental array magnetic behavior can be ascribed to a heterogeneous stray field induced by the diameter modulation, yielding a stronger interaction field at the wide extremity than at the narrow one. The results evidence the possibility to control the domain wall propagation and morphology by modulating the lateral aspect of the magnetic entity.

The time course of attention modulation elicited by spatial uncertainty.

Science.gov (United States)

Huang, Dan; Liang, Huilou; Xue, Linyan; Wang, Meijian; Hu, Qiyi; Chen, Yao

2017-09-01

Uncertainty regarding the target location is an influential factor for spatial attention. Modulation in spatial uncertainty can lead to adjustments in attention scope and variations in attention effects. Hence, investigating spatial uncertainty modulation is important for understanding the underlying mechanism of spatial attention. However, the temporal dynamics of this modulation remains unclear. To evaluate the time course of spatial uncertainty modulation, we adopted a Posner-like attention orienting paradigm with central or peripheral cues. Different numbers of cues were used to indicate the potential locations of the target and thereby manipulate the spatial uncertainty level. The time interval between the onsets of the cue and the target (stimulus onset asynchrony, SOA) varied from 50 to 2000ms. We found that under central cueing, the effect of spatial uncertainty modulation could be detected from 200 to 2000ms after the presence of the cues. Under peripheral cueing, the effect of spatial uncertainty modulation was observed from 50 to 2000ms after cueing. Our results demonstrate that spatial uncertainty modulation produces robust and sustained effects on target detection speed. The time course of this modulation is influenced by the cueing method, which suggests that discrepant processing procedures are involved under different cueing conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Molecular dissection of the mechanism by which EWS/FLI expression compromises actin cytoskeletal integrity and cell adhesion in Ewing sarcoma

Science.gov (United States)

Chaturvedi, Aashi; Hoffman, Laura M.; Jensen, Christopher C.; Lin, Yi-Chun; Grossmann, Allie H.; Randall, R. Lor; Lessnick, Stephen L.; Welm, Alana L.; Beckerle, Mary C.

2014-01-01

Ewing sarcoma is the second-most-common bone cancer in children. Driven by an oncogenic chromosomal translocation that results in the expression of an aberrant transcription factor, EWS/FLI, the disease is typically aggressive and micrometastatic upon presentation. Silencing of EWS/FLI in patient-derived tumor cells results in the altered expression of hundreds to thousands of genes and is accompanied by dramatic morphological changes in cytoarchitecture and adhesion. Genes encoding focal adhesion, extracellular matrix, and actin regulatory proteins are dominant targets of EWS/FLI-mediated transcriptional repression. Reexpression of genes encoding just two of these proteins, zyxin and α5 integrin, is sufficient to restore cell adhesion and actin cytoskeletal integrity comparable to what is observed when the EWS/FLI oncogene expression is compromised. Using an orthotopic xenograft model, we show that EWS/FLI-induced repression of α5 integrin and zyxin expression promotes tumor progression by supporting anchorage-independent cell growth. This selective advantage is paired with a tradeoff in which metastatic lung colonization is compromised. PMID:25057021

Freezing tolerance of sea urchin embryonic cells: Differentiation commitment and cytoskeletal disturbances in culture.

Science.gov (United States)

Odintsova, Nelly A; Ageenko, Natalya V; Kipryushina, Yulia O; Maiorova, Mariia A; Boroda, Andrey V

2015-08-01

This study focuses on the freezing tolerance of sea urchin embryonic cells. To significantly reduce the loss of physiological activity of these cells that occurs after cryopreservation and to study the effects of ultra-low temperatures on sea urchin embryonic cells, we tested the ability of the cells to differentiate into spiculogenic or pigment directions in culture, including an evaluation of the expression of some genes involved in pigment differentiation. A morphological analysis of cytoskeletal disturbances after freezing in a combination of penetrating (dimethyl sulfoxide and ethylene glycol) and non-penetrating (trehalose and polyvinylpyrrolidone) cryoprotectants revealed that the distribution pattern of filamentous actin and tubulin was similar to that in the control cultures. In contrast, very rare spreading cells and a small number of cells with filamentous actin and tubulin were detected after freezing in the presence of only non-penetrating cryoprotectants. The largest number of pigment cells was found in cultures frozen with trehalose or trehalose and dimethyl sulfoxide. The ability to induce the spicule formation was lost in the cells frozen only with non-penetrating cryoprotectants, while it was maximal in cultures frozen in a cryoprotective mixture containing both non-penetrating and penetrating cryoprotectants (particularly, when ethylene glycol was present). Using different markers for cell state assessment, an effective cryopreservation protocol for sea urchin cells was developed: three-step freezing with a low cooling rate (1-2°C/min) and a combination of non-penetrating and penetrating cryoprotectants made it possible to obtain a high level of cell viability (up to 65-80%). Copyright © 2015 Elsevier Inc. All rights reserved.

Fisetin antagonizes cell fusion, cytoskeletal organization and bone resorption in RANKL-differentiated murine macrophages.

Science.gov (United States)

Kim, Yun-Ho; Kim, Jung-Lye; Lee, Eun-Jung; Park, Sin-Hye; Han, Seon-Young; Kang, Soon Ah; Kang, Young-Hee

2014-03-01

Osteoclastogenesis is comprised of several stage s including progenitor survival, differentiation to mononuclear preosteoclasts, cell fusion to multinuclear mature osteoclasts, and activation to osteoclasts with bone resorbing activity. Botanical antioxidants are now being increasingly investigated for their health-promoting effects on bone. This study investigated that fisetin, a flavonol found naturally in many fruits and vegetables, suppressed osteoclastogenesis by disturbing receptor activator of nuclear factor (NF)-κB ligand (RANKL)-mediated signaling pathway and demoting osteoclastogenic protein induction. Nontoxic fisetin at ≤10 μM inhibited the induction of RANK, tumor necrosis factor receptor associated factor 6 (TRAF6) and the activation of NF-κB in RANKL-stimulated RAW 264.7 macrophages. In RANKL-differentiated osteoclasts cell fusion protein of E-cadherin was induced, which was dampened by fisetin. The formation of tartrate-resistance acid phosphatase-positive multinucleated osteoclasts was suppressed by adding fisetin to RANKL-exposed macrophages. It was also found that fisetin reduced actin ring formation and gelsolin induction of osteclasts enhanced by RANKL through disturbing c-Src-proline-rich tyrosine kinase 2 signaling. Fisetin deterred preosteoclasts from the cell-cell fusion and the organization of the cytoskeleton to seal the resorbing area and to secret protons for bone resorption. Consistently, the 5 day-treatment of fisetin diminished RANKL-induced cellular expression of carbonic anhydrase II and integrin β3 concurrently with a reduction of osteoclast bone-resorbing activity. Therefore, fisetin was a natural therapeutic agent retarding osteoclast fusion and cytoskeletal organization such as actin rings and ruffled boarder, which is a property of mature osteoclasts and is required for osteoclasts to resorb bone. Copyright © 2014 Elsevier Inc. All rights reserved.

Acousto-plasmofluidics: Acoustic modulation of surface plasmon resonance in microfluidic systems

Directory of Open Access Journals (Sweden)

Daniel Ahmed

2015-09-01

Full Text Available We acoustically modulated the localized surface plasmon resonances (LSPRs of metal nanostructures integrated within microfluidic systems. An acoustically driven micromixing device based on bubble microstreaming quickly and homogeneously mixes multiple laminar flows of different refractive indices. The altered refractive index of the mixed fluids enables rapid modulation of the LSPRs of gold nanodisk arrays embedded within the microfluidic channel. The device features fast response for dynamic operation, and the refractive index within the channel is tailorable. With these unique features, our “acousto-plasmofluidic” device can be useful in applications such as optical switches, modulators, filters, biosensors, and lab-on-a-chip systems.

Magnetoplasmons in gapped graphene in a periodically modulated magnetic field

KAUST Repository

Tahir, Muhammad

2016-01-08

Motivated by recent experiments on long-lived magnetoplasmons in the presence of a perpendicular magnetic field, we investigate the dynamical dielectric response function of graphene in contact with a substrate using the random phase approximation. We add a periodically modulated magnetic field within the graphene plane and address both the inter and intra Landau band magnetoplasmons. Verification of the predicted magnetic modulation effects is possible by experiments analogous to those for the zero gap limit. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA.

Validity of High School Physic Module With Character Values Using Process Skill Approach In STKIP PGRI West Sumatera

Science.gov (United States)

Anaperta, M.; Helendra, H.; Zulva, R.

2018-04-01

This study aims to describe the validity of physics module with Character Oriented Values Using Process Approach Skills at Dynamic Electrical Material in high school physics / MA and SMK. The type of research is development research. The module development model uses the development model proposed by Plomp which consists of (1) preliminary research phase, (2) the prototyping phase, and (3) assessment phase. In this research is done is initial investigation phase and designing. Data collecting technique to know validation is observation and questionnaire. In the initial investigative phase, curriculum analysis, student analysis, and concept analysis were conducted. In the design phase and the realization of module design for SMA / MA and SMK subjects in dynamic electrical materials. After that, the formative evaluation which include self evaluation, prototyping (expert reviews, one-to-one, and small group. At this stage validity is performed. This research data is obtained through the module validation sheet, which then generates a valid module.

Periodic precursors of nonlinear dynamical transitions

International Nuclear Information System (INIS)

Jiang Yu; Dong Shihai; Lozada-Cassou, M.

2004-01-01

We study the resonant response of a nonlinear system to external periodic perturbations. We show by numerical simulation that the periodic resonance curve may anticipate the dynamical instability of the unperturbed nonlinear periodic system, at parameter values far away from the bifurcation points. In the presence of noise, the buried intrinsic periodic dynamics can be picked out by analyzing the system's response to periodic modulation of appropriate intensity

Variability and Order in Cytoskeletal Dynamics of Motile Amoeboid Cells

Science.gov (United States)

Hsu, Hsin-Fang; Bodenschatz, Eberhard; Westendorf, Christian; Gholami, Azam; Pumir, Alain; Tarantola, Marco; Beta, Carsten

2017-10-01

The chemotactic motion of eukaryotic cells such as leukocytes or metastatic cancer cells relies on membrane protrusions driven by the polymerization and depolymerization of actin. Here we show that the response of the actin system to a receptor stimulus is subject to a threshold value that varies strongly from cell to cell. Above the threshold, we observe pronounced cell-to-cell variability in the response amplitude. The polymerization time, however, is almost constant over the entire range of response amplitudes, while the depolymerization time increases with increasing amplitude. We show that cell-to-cell variability in the response amplitude correlates with the amount of Arp2 /3 , a protein that enhances actin polymerization. A time-delayed feedback model for the cortical actin concentration is consistent with all our observations and confirms the role of Arp2 /3 in the observed cell-to-cell variability. Taken together, our observations highlight robust regulation of the actin response that enables a reliable timing of cell movement.

Regulation of cytoskeletal dynamics by phospholipase D and phosphatidic acid

Czech Academy of Sciences Publication Activity Database

Pleskot, Roman; Li, J.J.; Žárský, Viktor; Potocký, Martin; Staiger, C.J.

2013-01-01

Roč. 18, č. 9 (2013), s. 496-504 ISSN 1360-1385 R&D Projects: GA ČR GA13-19073S Institutional research plan: CEZ:AV0Z50380511 Keywords : cytoskeleton * microtubules * phosphatidic acid Subject RIV: ED - Physiology Impact factor: 13.479, year: 2013

Directed selective-tunneling of bosons with periodically modulated interaction

International Nuclear Information System (INIS)

Lu, Gengbiao; Fu, Li-Bin; Hai, Wenhua; Zou, Mingliang; Guo, Yu

2015-01-01

We study the tunneling dynamics of bosons with periodically modulated interaction held in a triple-well potential. In high-frequency approximation, we derive a set of reduced coupled equations and the corresponding Floquet solutions are obtained. Based on the analytical results and their numerical correspondence, the directed selective-tunneling effect of a single atom is demonstrated when all bosons are prepared in middle well initially. A scheme for separating a single atom from N bosons is presented, in which the atom can be trapped in right or left well by adjusting the modulation strength. - Highlights: • The Floquet solutions in a modulating triple-well are obtained analytically. • The directed selective-tunneling effect of a single atom is demonstrated. • We present a manipulation scheme for separating a single atom from N bosons

Signed Young Modules and Simple Specht Modules

OpenAIRE

Danz, Susanne; Lim, Kay Jin

2015-01-01

By a result of Hemmer, every simple Specht module of a finite symmetric group over a field of odd characteristic is a signed Young module. While Specht modules are parametrized by partitions, indecomposable signed Young modules are parametrized by certain pairs of partitions. The main result of this article establishes the signed Young module labels of simple Specht modules. Along the way we prove a number of results concerning indecomposable signed Young modules that are of independent inter...

Effective refractive index modulation based optical fiber humidity sensor employing etched fiber Bragg grating

Science.gov (United States)

Mundendhar, Pathi; Khijwania, Sunil K.

2015-09-01

Relative humidity (RH) sensor employing etched fiber Bragg grating (FBG) is reported where RH variations are captured using effective-index-modulation, rather than traditional strain-modulation. Additionly, linear sensor response over wide dynamic range with optimum characteristics is focused. Comprehensive experimental investigation is carried out for the sensor that comprises uniformly etched cladding in the FBG region. Obtained results are observed to be in agreement with the theoretical analysis. Sensor response is observed to be linear over dynamic range 3-94%RH with ~ 0.082 pm/%RH sensitivity, ~0.6%RH resolution, ~ +/-2.5%RH accuracy, ~ +/-0.2 pm average discrepancy and ~ 0.2s response time during humidification/desiccation.

Mechanical Cushion Design Influence on Cylinder Dynamics

DEFF Research Database (Denmark)

Borghi, Massimo; Milani, Massimo; Conrad, Finn

2005-01-01

. experimental comparison, involving the piston velocity and the cylinder chambers pressure. After, with the aim of highlighting the effect of mechanical cushions design on a two effect linear actuator dynamic performances, the characteristics modulation of four alternative cushioning systems are determined......The paper deals with the simulation and the experimental verification of the dynamic behaviour of a linear actuator equipped with different configurations of mechanical cushion. A numerical model, developed and tailored to describe the influence of different modulation of the discharged flow......-rate (and of the correspondent discharging orifice design) on the cushioning characteristics variation is firstly introduced. Then, with respect to the case of the cylindrical cushioning engagement, both the reliability and the limits of the numerical approach are highlighted through a numerical vs...

Distinct activities of Bartonella henselae type IV secretion effector proteins modulate capillary-like sprout formation.

Science.gov (United States)

Scheidegger, F; Ellner, Y; Guye, P; Rhomberg, T A; Weber, H; Augustin, H G; Dehio, C

2009-07-01

The zoonotic pathogen Bartonella henselae (Bh) can lead to vasoproliferative tumour lesions in the skin and inner organs known as bacillary angiomatosis and bacillary peliosis. The knowledge on the molecular and cellular mechanisms involved in this pathogen-triggered angiogenic process is confined by the lack of a suitable animal model and a physiologically relevant cell culture model of angiogenesis. Here we employed a three-dimensional in vitro angiogenesis assay of collagen gel-embedded endothelial cell (EC) spheroids to study the angiogenic properties of Bh. Spheroids generated from Bh-infected ECs displayed a high capacity to form sprouts, which represent capillary-like projections into the collagen gel. The VirB/VirD4 type IV secretion system and a subset of its translocated Bartonella effector proteins (Beps) were found to profoundly modulate this Bh-induced sprouting activity. BepA, known to protect ECs from apoptosis, strongly promoted sprout formation. In contrast, BepG, triggering cytoskeletal rearrangements, potently inhibited sprouting. Hence, the here established in vitro model of Bartonella- induced angiogenesis revealed distinct and opposing activities of type IV secretion system effector proteins, which together with a VirB/VirD4-independent effect may control the angiogenic activity of Bh during chronic infection of the vasculature.

Nucleus and nucleus-cytoskeleton connections in 3D cell migration

Energy Technology Data Exchange (ETDEWEB)

Liu, Lingling, E-mail: liulingling2012@163.com; Luo, Qing, E-mail: qing.luo@cqu.edu.cn; Sun, Jinghui, E-mail: sunjhemail@163.com; Song, Guanbin, E-mail: song@cqu.edu.cn

2016-10-15

Cell migration plays an important role in many physiological and pathological settings, ranging from embryonic development to cancer metastasis. Currently, accumulating data suggest that cells migrating in three-dimensional (3D) environments show well-defined differences compared to their well-established two-dimensional (2D) counterparts. During 3D migration, the cell body and nucleus must deform to allow cellular passage through the available spaces, and the deformability of the relatively rigid nucleus may constitute a limiting step. Here, we highlight the key evidence regarding the role of the nuclear mechanics in 3D migration, including the molecular components that govern the stiffness of the nucleus and review how the nuclear dynamics are connected to and controlled by cytoskeleton-based migration machinery. Intriguingly, nuclear movement must be coordinated with the cytoskeletal dynamics at the leading and trailing edges, which in turn impact the cytoplasmic dynamics that affect the migration efficiency. Thus, we suggest that alterations in the nuclear structure may facilitate cellular reorganizations that are necessary for efficient migration. - Graphical abstract: Schematic representations of a cell migrating on a 2D substrate and a cell migrating in a 3D extracellular matrix environment. (A) Nucleus-cytoskeleton connections are essential to 3D migration. Mechanical signals are transduced by integrins at the cell surface and channeled to cytoskeletal proteins, which generates prestress. The nucleus-cytoskeleton connections can either act as a stable skeleton to anchor the nuclei or provide active force to move the nuclei. The LINC complex is responsible for the nucleo-cytoskeletal coupling. Nesprins connect the cytoskeletal proteins to the inner nuclear membrane proteins SUN1 and SUN2. The SUN proteins connect to the lamins that form the lamina, which attaches to the chromatin. This physical connectivity transmits the mechanical signals from receptors at

Nucleus and nucleus-cytoskeleton connections in 3D cell migration

International Nuclear Information System (INIS)

Liu, Lingling; Luo, Qing; Sun, Jinghui; Song, Guanbin

2016-01-01

Cell migration plays an important role in many physiological and pathological settings, ranging from embryonic development to cancer metastasis. Currently, accumulating data suggest that cells migrating in three-dimensional (3D) environments show well-defined differences compared to their well-established two-dimensional (2D) counterparts. During 3D migration, the cell body and nucleus must deform to allow cellular passage through the available spaces, and the deformability of the relatively rigid nucleus may constitute a limiting step. Here, we highlight the key evidence regarding the role of the nuclear mechanics in 3D migration, including the molecular components that govern the stiffness of the nucleus and review how the nuclear dynamics are connected to and controlled by cytoskeleton-based migration machinery. Intriguingly, nuclear movement must be coordinated with the cytoskeletal dynamics at the leading and trailing edges, which in turn impact the cytoplasmic dynamics that affect the migration efficiency. Thus, we suggest that alterations in the nuclear structure may facilitate cellular reorganizations that are necessary for efficient migration. - Graphical abstract: Schematic representations of a cell migrating on a 2D substrate and a cell migrating in a 3D extracellular matrix environment. (A) Nucleus-cytoskeleton connections are essential to 3D migration. Mechanical signals are transduced by integrins at the cell surface and channeled to cytoskeletal proteins, which generates prestress. The nucleus-cytoskeleton connections can either act as a stable skeleton to anchor the nuclei or provide active force to move the nuclei. The LINC complex is responsible for the nucleo-cytoskeletal coupling. Nesprins connect the cytoskeletal proteins to the inner nuclear membrane proteins SUN1 and SUN2. The SUN proteins connect to the lamins that form the lamina, which attaches to the chromatin. This physical connectivity transmits the mechanical signals from receptors at

Evaluation of a software module for adaptive treatment planning and re-irradiation.

Science.gov (United States)

Richter, Anne; Weick, Stefan; Krieger, Thomas; Exner, Florian; Kellner, Sonja; Polat, Bülent; Flentje, Michael

2017-12-28

The aim of this work is to validate the Dynamic Planning Module in terms of usability and acceptance in the treatment planning workflow. The Dynamic Planning Module was used for decision making whether a plan adaptation was necessary within one course of radiation therapy. The Module was also used for patients scheduled for re-irradiation to estimate the dose in the pretreated region and calculate the accumulated dose to critical organs at risk. During one year, 370 patients were scheduled for plan adaptation or re-irradiation. All patient cases were classified according to their treated body region. For a sub-group of 20 patients treated with RT for lung cancer, the dosimetric effect of plan adaptation during the main treatment course was evaluated in detail. Changes in tumor volume, frequency of re-planning and the time interval between treatment start and plan adaptation were assessed. The Dynamic Planning Tool was used in 20% of treated patients per year for both approaches nearly equally (42% plan adaptation and 58% re-irradiation). Most cases were assessed for the thoracic body region (51%) followed by pelvis (21%) and head and neck cases (10%). The sub-group evaluation showed that unintended plan adaptation was performed in 38% of the scheduled cases. A median time span between first day of treatment and necessity of adaptation of 17 days (range 4-35 days) was observed. PTV changed by 12 ± 12% on average (maximum change 42%). PTV decreased in 18 of 20 cases due to tumor shrinkage and increased in 2 of 20 cases. Re-planning resulted in a reduction of the mean lung dose of the ipsilateral side in 15 of 20 cases. The experience of one year showed high acceptance of the Dynamic Planning Module in our department for both physicians and medical physicists. The re-planning can potentially reduce the accumulated dose to the organs at risk and ensure a better target volume coverage. In the re-irradiation situation, the Dynamic Planning Tool was used to