Cep169, a Novel Microtubule Plus-End-Tracking Centrosomal Protein, Binds to CDK5RAP2 and Regulates Microtubule Stability.

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Yusuke Mori

Full Text Available The centrosomal protein, CDK5RAP2, is a microcephaly protein that regulates centrosomal maturation by recruitment of a γ-tubulin ring complex (γ-TuRC onto centrosomes. In this report, we identified a novel human centrosomal protein, Cep169, as a binding partner of CDK5RAP2, a member of microtubule plus-end-tracking proteins (+TIPs. Cep169 interacts directly with CDK5RAP2 through CM1, an evolutionarily conserved domain, and colocalizes at the pericentriolar matrix (PCM around centrioles with CDK5RAP2. In addition, Cep169 interacts with EB1 through SxIP-motif responsible for EB1 binding, and colocalizes with CDK5RAP2 at the microtubule plus-end. EB1-binding-deficient Cep169 abolishes EB1 interaction and microtubule plus-end attachment, indicating Cep169 as a novel member of +TIPs. We further show that ectopic expression of either Cep169 or CDK5RAP2 induces microtubule bundling and acetylation in U2OS cells, and depletion of Cep169 induces microtubule depolymerization in HeLa cells, although Cep169 is not required for assembly of γ-tubulin onto centrosome by CDK5RAP2. These results show that Cep169 targets microtubule tips and regulates stability of microtubules with CDK5RAP2.

A qualitative, interprofessional analysis of barriers to and facilitators of implementation of the Department of Veterans Affairs' Clostridium difficile prevention bundle using a human factors engineering approach.

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Yanke, Eric; Moriarty, Helene; Carayon, Pascale; Safdar, Nasia

2018-03-01

Clostridium difficile infection (CDI) is increasingly prevalent, severe, and costly. Adherence to infection prevention practices remains suboptimal. More effective strategies to implement guidelines and evidence are needed. Interprofessional focus groups consisting of physicians, resident physicians, nurses, and health technicians were conducted for a quality improvement project evaluating adherence to the Department of Veterans Affairs' (VA) nationally mandated C difficile prevention bundle. Qualitative analysis with a visual matrix display identified barrier and facilitator themes guided by the Systems Engineering Initiative for Patient Safety model, a human factors engineering approach. Several themes, encompassing both barriers and facilitators to bundle adherence, emerged. Rapid turnaround time of C difficile polymerase chain reaction testing was a facilitator of timely diagnosis. Too few, poorly located, and cluttered sinks were barriers to appropriate hand hygiene. Patient care workload and the time-consuming process of contact isolation precautions were also barriers to adherence. Multiple work system components serve as barriers to and facilitators of adherence to the VA CDI prevention bundle among an interprofessional group of health care workers. Organizational factors appear to significantly influence bundle adherence. Interprofessional perspectives are needed to identify barriers to and facilitators of bundle implementation, which is a necessary first step to address adherence to bundled infection prevention practices. Published by Elsevier Inc.

Capture of microtubule plus-ends at the actin cortex promotes axophilic neuronal migration by enhancing microtubule tension in the leading process.

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Hutchins, B Ian; Wray, Susan

2014-01-01

Microtubules are a critical part of neuronal polarity and leading process extension, thus microtubule movement plays an important role in neuronal migration. However, the dynamics of microtubules during the forward movement of the nucleus into the leading process (nucleokinesis) is unclear and may be dependent on the cell type and mode of migration used. In particular, little is known about cytoskeletal changes during axophilic migration, commonly used in anteroposterior neuronal migration. We recently showed that leading process actin flow in migrating GnRH neurons is controlled by a signaling cascade involving IP3 receptors, CaMKK, AMPK, and RhoA. In the present study, microtubule dynamics were examined in GnRH neurons. Failure of the migration of these cells leads to the neuroendocrine disorder Kallmann Syndrome. Microtubules translocated forward along the leading process shaft during migration, but reversed direction and moved toward the nucleus when migration stalled. Blocking calcium release through IP3 receptors halted migration and induced the same reversal of microtubule translocation, while blocking cortical actin flow prevented microtubules from translocating toward the distal leading process. Super-resolution imaging revealed that microtubule plus-end tips are captured at the actin cortex through calcium-dependent mechanisms. This work shows that cortical actin flow draws the microtubule network forward through calcium-dependent capture in order to promote nucleokinesis, revealing a novel mechanism engaged by migrating neurons to facilitate movement.

TONNEAU2/FASS Regulates the Geometry of Microtubule Nucleation and Cortical Array Organization in Interphase Arabidopsis Cells[C][W

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Kirik, Angela; Ehrhardt, David W.; Kirik, Viktor

2012-01-01

Organization of microtubules into ordered arrays involves spatial and temporal regulation of microtubule nucleation. Here, we show that acentrosomal microtubule nucleation in plant cells involves a previously unknown regulatory step that determines the geometry of microtubule nucleation. Dynamic imaging of interphase cortical microtubules revealed that the ratio of branching to in-bundle microtubule nucleation on cortical microtubules is regulated by the Arabidopsis thaliana B′′ subunit of protein phosphatase 2A, which is encoded by the TONNEAU2/FASS (TON2) gene. The probability of nucleation from γ-tubulin complexes localized at the cell cortex was not affected by a loss of TON2 function, suggesting a specific role of TON2 in regulating the nucleation geometry. Both loss of TON2 function and ectopic targeting of TON2 to the plasma membrane resulted in defects in cell shape, suggesting the importance of TON2-mediated regulation of the microtubule cytoskeleton in cell morphogenesis. Loss of TON2 function also resulted in an inability for cortical arrays to reorient in response to light stimulus, suggesting an essential role for TON2 and microtubule branching nucleation in reorganization of microtubule arrays. Our data establish TON2 as a regulator of interphase microtubule nucleation and provide experimental evidence for a novel regulatory step in the process of microtubule-dependent nucleation. PMID:22395485

Microtubule heterogeneity of Ornithogalum umbellatum ovary epidermal cells: non-stable cortical microtubules and stable lipotubuloid microtubules.

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Kwiatkowska, Maria; Stępiński, Dariusz; Polit, Justyna T; Popłońska, Katarzyna; Wojtczak, Agnieszka

2011-01-01

Lipotubuloids, structures containing lipid bodies and microtubules, are described in ovary epidermal cells of Ornithogalum umbellatum. Microtubules of lipotubuloids can be fixed in electron microscope fixative containing only buffered OsO(4) or in glutaraldehyde with OsO(4) post-fixation, or in a mixture of OsO(4) and glutaraldehyde. None of these substances fixes cortical microtubules of ovary epidermis of this plant which is characterized by dynamic longitudinal growth. However, cortical microtubules can be fixed with cold methanol according immunocytological methods with the use of β-tubulin antibodies and fluorescein. The existence of cortical microtubules has also been evidenced by EM observations solely after the use of taxol, microtubule stabilizer, and fixation in a glutaraldehyde/OsO(4) mixture. These microtubules mostly lie transversely, sometimes obliquely, and rarely parallel to the cell axis. Staining, using Ruthenium Red and silver hexamine, has revealed that lipotubuloid microtubules surface is covered with polysaccharides. The presumption has been made that the presence of a polysaccharide layer enhances the stability of lipotubuloid microtubules.

Linking cortical microtubule attachment and exocytosis [version 1; referees: 2 approved

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Ivar Noordstra

2017-04-01

Full Text Available Exocytosis is a fundamental cellular process whereby secreted molecules are packaged into vesicles that move along cytoskeletal filaments and fuse with the plasma membrane. To function optimally, cells are strongly dependent on precisely controlled delivery of exocytotic cargo. In mammalian cells, microtubules serve as major tracks for vesicle transport by motor proteins, and thus microtubule organization is important for targeted delivery of secretory carriers. Over the years, multiple microtubule-associated and cortical proteins have been discovered that facilitate the interaction between the microtubule plus ends and the cell cortex. In this review, we focus on mammalian protein complexes that have been shown to participate in both cortical microtubule capture and exocytosis, thereby regulating the spatial organization of secretion. These complexes include microtubule plus-end tracking proteins, scaffolding factors, actin-binding proteins, and components of vesicle docking machinery, which together allow efficient coordination of cargo transport and release.

Molecular mechanism of bundle formation by the bacterial actin ParM

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Popp, David, E-mail: dpopp@imcb.a-star.edu.sg [ERATO ' Actin Filament Dynamics' Project, Japan Science and Technology Corporation, c/o RIKEN Harima Institute at Spring 8, 1-1-1 Kouto, Sayo, Hyogo 679-5148 (Japan); Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, 138673 Singapore (Singapore); Narita, Akihiro [ERATO ' Actin Filament Dynamics' Project, Japan Science and Technology Corporation, c/o RIKEN Harima Institute at Spring 8, 1-1-1 Kouto, Sayo, Hyogo 679-5148 (Japan); Nagoya University Graduate School of Science, Structural Biology Research Center and Division of Biological Sciences, Furo-cho, Chikusa-ku, Nagoya 464-8601 (Japan); Iwasa, Mitsusada [ERATO ' Actin Filament Dynamics' Project, Japan Science and Technology Corporation, c/o RIKEN Harima Institute at Spring 8, 1-1-1 Kouto, Sayo, Hyogo 679-5148 (Japan); Maeda, Yuichiro [ERATO ' Actin Filament Dynamics' Project, Japan Science and Technology Corporation, c/o RIKEN Harima Institute at Spring 8, 1-1-1 Kouto, Sayo, Hyogo 679-5148 (Japan); Nagoya University Graduate School of Science, Structural Biology Research Center and Division of Biological Sciences, Furo-cho, Chikusa-ku, Nagoya 464-8601 (Japan); Robinson, Robert C. [Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, 138673 Singapore (Singapore)

2010-01-22

The actin homolog ParM plays a microtubule-like role in segregating DNA prior to bacterial cell division. Fluorescence and cryo-electron microscopy have shown that ParM forms filament bundles between separating DNA plasmids in vivo. Given the lack of ParM bundling proteins it remains unknown how ParM bundles form at the molecular level. Here we show using time-lapse TIRF microscopy, under in vitro molecular crowding conditions, that ParM-bundle formation consists of two distinct phases. At the onset of polymerization bundle thickness and shape are determined in the form of nuclei of short helically disordered filaments arranged in a liquid-like lattice. These nuclei then undergo an elongation phase whereby they rapidly increase in length. At steady state, ParM bundles fuse into one single large aggregate. This behavior had been predicted by theory but has not been observed for any other cytomotive biopolymer, including F-actin. We employed electron micrographs of ParM rafts, which are 2-D analogs of 3-D bundles, to identify the main molecular interfilament contacts within these suprastructures. The interface between filaments is similar for both parallel and anti-parallel orientations and the distribution of filament polarity is random within a bundle. We suggest that the interfilament interactions are not due to the interactions of specific residues but rather to long-range, counter ion mediated, electrostatic attractive forces. A randomly oriented bundle ensures that the assembly is rigid and that DNA may be captured with equal efficiency at both ends of the bundle via the ParR binding protein.

Microtubule-Organizing Centers.

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Wu, Jingchao; Akhmanova, Anna

2017-10-06

The organization of microtubule networks is crucial for controlling chromosome segregation during cell division, for positioning and transport of different organelles, and for cell polarity and morphogenesis. The geometry of microtubule arrays strongly depends on the localization and activity of the sites where microtubules are nucleated and where their minus ends are anchored. Such sites are often clustered into structures known as microtubule-organizing centers, which include the centrosomes in animals and spindle pole bodies in fungi. In addition, other microtubules, as well as membrane compartments such as the cell nucleus, the Golgi apparatus, and the cell cortex, can nucleate, stabilize, and tether microtubule minus ends. These activities depend on microtubule-nucleating factors, such as γ-tubulin-containing complexes and their activators and receptors, and microtubule minus end-stabilizing proteins with their binding partners. Here, we provide an overview of the current knowledge on how such factors work together to control microtubule organization in different systems.

SDF1 Reduces Interneuron Leading Process Branching through Dual Regulation of Actin and Microtubules

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Lysko, Daniel E.; Putt, Mary

2014-01-01

Normal cerebral cortical function requires a highly ordered balance between projection neurons and interneurons. During development these two neuronal populations migrate from distinct progenitor zones to form the cerebral cortex, with interneurons originating in the more distant ganglionic eminences. Moreover, deficits in interneurons have been linked to a variety of neurodevelopmental disorders underscoring the importance of understanding interneuron development and function. We, and others, have identified SDF1 signaling as one important modulator of interneuron migration speed and leading process branching behavior in mice, although how SDF1 signaling impacts these behaviors remains unknown. We previously found SDF1 inhibited leading process branching while increasing the rate of migration. We have now mechanistically linked SDF1 modulation of leading process branching behavior to a dual regulation of both actin and microtubule organization. We find SDF1 consolidates actin at the leading process tip by de-repressing calpain protease and increasing proteolysis of branched-actin-supporting cortactin. Additionally, SDF1 stabilizes the microtubule array in the leading process through activation of the microtubule-associated protein doublecortin (DCX). DCX stabilizes the microtubule array by bundling microtubules within the leading process, reducing branching. These data provide mechanistic insight into the regulation of interneuron leading process dynamics during neuronal migration in mice and provides insight into how cortactin and DCX, a known human neuronal migration disorder gene, participate in this process. PMID:24695713

SDF1 reduces interneuron leading process branching through dual regulation of actin and microtubules.

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Lysko, Daniel E; Putt, Mary; Golden, Jeffrey A

2014-04-02

Normal cerebral cortical function requires a highly ordered balance between projection neurons and interneurons. During development these two neuronal populations migrate from distinct progenitor zones to form the cerebral cortex, with interneurons originating in the more distant ganglionic eminences. Moreover, deficits in interneurons have been linked to a variety of neurodevelopmental disorders underscoring the importance of understanding interneuron development and function. We, and others, have identified SDF1 signaling as one important modulator of interneuron migration speed and leading process branching behavior in mice, although how SDF1 signaling impacts these behaviors remains unknown. We previously found SDF1 inhibited leading process branching while increasing the rate of migration. We have now mechanistically linked SDF1 modulation of leading process branching behavior to a dual regulation of both actin and microtubule organization. We find SDF1 consolidates actin at the leading process tip by de-repressing calpain protease and increasing proteolysis of branched-actin-supporting cortactin. Additionally, SDF1 stabilizes the microtubule array in the leading process through activation of the microtubule-associated protein doublecortin (DCX). DCX stabilizes the microtubule array by bundling microtubules within the leading process, reducing branching. These data provide mechanistic insight into the regulation of interneuron leading process dynamics during neuronal migration in mice and provides insight into how cortactin and DCX, a known human neuronal migration disorder gene, participate in this process.

Microtubule catastrophe and rescue.

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Gardner, Melissa K; Zanic, Marija; Howard, Jonathon

2013-02-01

Microtubules are long cylindrical polymers composed of tubulin subunits. In cells, microtubules play an essential role in architecture and motility. For example, microtubules give shape to cells, serve as intracellular transport tracks, and act as key elements in important cellular structures such as axonemes and mitotic spindles. To accomplish these varied functions, networks of microtubules in cells are very dynamic, continuously remodeling through stochastic length fluctuations at the ends of individual microtubules. The dynamic behavior at the end of an individual microtubule is termed 'dynamic instability'. This behavior manifests itself by periods of persistent microtubule growth interrupted by occasional switching to rapid shrinkage (called microtubule 'catastrophe'), and then by switching back from shrinkage to growth (called microtubule 'rescue'). In this review, we summarize recent findings which provide new insights into the mechanisms of microtubule catastrophe and rescue, and discuss the impact of these findings in regards to the role of microtubule dynamics inside of cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

Barriers and facilitators towards implementing the Sepsis Six care bundle (BLISS-1): a mixed methods investigation using the theoretical domains framework.

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Roberts, Neil; Hooper, Guy; Lorencatto, Fabiana; Storr, Wendell; Spivey, Michael

2017-09-19

The 'Sepsis 6', a care bundle of basic, but vital, measures (e.g. intravenous fluid, antibiotics) has been implemented to improve sepsis treatment. However, uptake has been variable. Tools from behavioral sciences, such as the Theoretical Domains Framework (TDF) may be used to understand and address such implementation issues. This study used a behavioral science approach to identify barriers and facilitators towards Sepsis Six implementation at a case study hospital. Semi-structured interviews based on the TDF were conducted with a sample group of consultants, junior doctors and nurses from Emergency Department, Medical and Surgical Admissions, to explore barriers/facilitators to Sepsis Six performance. Transcripts were analyzed following the combined principles of content and framework analysis. Emerging themes informed a questionnaire to explore generalizability and importance across a sample of 261 stakeholders. Median importance and agreement ratings for each theme were calculated overall and for each role and clinical area. These were used to identify important barriers and important facilitators as targets for performance improvement. No new belief statements were discovered and data saturation was deemed achieved after 10 interviews. 1699 utterances were coded into 64 belief statements, then collated into a 51-item questionnaire. 113 questionnaire responses were obtained (44.3% response rate). Important barriers included insufficient audit and feedback, poor teamwork and communication, concerns about using the Sepsis Six in certain patients, insufficient training, and resource concerns. Facilitators included confidence in knowledge and skills, beliefs in overall benefits of the bundle, beliefs that identification and management of septic patients fell within everyone's role, and that regular use of the bundle made it easier to remember. Some beliefs were applicable for the entire group, others were specific to particular staff groups. A range of barriers

Wood cell-wall structure requires local 2D-microtubule disassembly by a novel plasma membrane-anchored protein.

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Oda, Yoshihisa; Iida, Yuki; Kondo, Yuki; Fukuda, Hiroo

2010-07-13

Plant cells have evolved cortical microtubules, in a two-dimensional space beneath the plasma membrane, that regulate patterning of cellulose deposition. Although recent studies have revealed that several microtubule-associated proteins facilitate self-organization of transverse cortical microtubules, it is still unknown how diverse patterns of cortical microtubules are organized in different xylem cells, which are the major components of wood. Using our newly established in vitro xylem cell differentiation system, we found that a novel microtubule end-tracking protein, microtubule depletion domain 1 (MIDD1), was anchored to distinct plasma membrane domains and promoted local microtubule disassembly, resulting in pits on xylem cell walls. The introduction of RNA interference for MIDD1 resulted in the failure of local microtubule depletion and the formation of secondary walls without pits. Conversely, the overexpression of MIDD1 reduced microtubule density. MIDD1 has two coiled-coil domains for the binding to microtubules and for the anchorage to plasma membrane domains, respectively. Combination of the two coils caused end tracking of microtubules during shrinkage and suppressed their rescue events. Our results indicate that MIDD1 integrates spatial information in the plasma membrane with cortical microtubule dynamics for determining xylem cell wall pattern. Copyright 2010 Elsevier Ltd. All rights reserved.

Microtubule Catastrophe and Rescue

OpenAIRE

Gardner, Melissa K.; Zanic, Marija; Howard, Jonathon

2012-01-01

Microtubules are long cylindrical polymers composed of tubulin subunits. In cells, microtubules play an essential role in architecture and motility. For example, microtubules give shape to cells, serve as intracellular transport tracks, and act as key elements in important cellular structures such as axonemes and mitotic spindles. To accomplish these varied functions, networks of microtubules in cells are very dynamic, continuously remodeling through stochastic length fluctuations at the ends...

Arabidopsis Microtubule-Associated Protein MAP65-3 Cross-Links Antiparallel Microtubules toward Their Plus Ends in the Phragmoplast via Its Distinct C-Terminal Microtubule Binding Domain[W

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Ho, Chin-Min Kimmy; Lee, Yuh-Ru Julie; Kiyama, Lindsay D.; Dinesh-Kumar, Savithramma P.; Liu, Bo

2012-01-01

Plant cytokinesis is brought about by the phragmoplast, which contains an antiparallel microtubule (MT) array. The MT-associated protein MAP65-3 acts as an MT-bundling factor that specifically cross-links antiparallel MTs near their plus ends. MAP65 family proteins contain an N-terminal dimerization domain and C-terminal MT interaction domain. Compared with other MAP65 isoforms, MAP65-3 contains an extended C terminus. A MT binding site was discovered in the region between amino acids 496 and 588 and found to be essential for the organization of phragmoplast MTs. The frequent cytokinetic failure caused by loss of MAP65-3 was not rescued by ectopic expression of MAP65-1 under the control of the MAP65-3 promoter, indicating nonoverlapping functions between the two isoforms. In the presence of MAP65-3, however, ectopic MAP65-1 appeared in the phragmoplast midline. We show that MAP65-1 could acquire the function of MAP65-3 when the C terminus of MAP65-3, which contains the MT binding site, was grafted to it. Our results also show that MAP65-1 and MAP65-3 may share redundant functions in MT stabilization. Such a stabilization effect was likely brought about by MT binding and bundling. We conclude that MAP65-3 contains a distinct C-terminal MT binding site with a specific role in cross-linking antiparallel MTs toward their plus ends in the phragmoplast. PMID:22570443

Nuclear fuel bundle disassembly and assembly tool

International Nuclear Information System (INIS)

Yates, J.; Long, J.W.

1975-01-01

A nuclear power reactor fuel bundle is described which has a plurality of tubular fuel rods disposed in parallel array between two transverse tie plates. It is secured against disassembly by one or more locking forks which engage slots in tie rods which position the transverse plates. Springs mounted on the fuel and tie rods are compressed when the bundle is assembled thereby maintaining a continual pressure against the locking forks. Force applied in opposition to the springs permits withdrawal of the locking forks so that one tie plate may be removed, giving access to the fuel rods. An assembly and disassembly tool facilitates removal of the locking forks when the bundle is to be disassembled and the placing of the forks during assembly of the bundle. (U.S.)

Tokyo Guidelines 2018: management bundles for acute cholangitis and cholecystitis

NARCIS (Netherlands)

Mayumi, Toshihiko; Okamoto, Kohji; Takada, Tadahiro; Strasberg, Steven M.; Solomkin, Joseph S.; Schlossberg, David; Pitt, Henry A.; Yoshida, Masahiro; Gomi, Harumi; Miura, Fumihiko; Garden, O. James; Kiriyama, Seiki; Yokoe, Masamichi; Endo, Itaru; Asbun, Horacio J.; Iwashita, Yukio; Hibi, Taizo; Umezawa, Akiko; Suzuki, Kenji; Itoi, Takao; Hata, Jiro; Han, Ho-Seong; Hwang, Tsann-Long; Dervenis, Christos; Asai, Koji; Mori, Yasuhisa; Huang, Wayne Shih-Wei; Belli, Giulio; Mukai, Shuntaro; Jagannath, Palepu; Cherqui, Daniel; Kozaka, Kazuto; Baron, Todd H.; de Santibañes, Eduardo; Higuchi, Ryota; Wada, Keita; Gouma, Dirk J.; Deziel, Daniel J.; Liau, Kui-Hin; Wakabayashi, Go; Padbury, Robert; Jonas, Eduard; Supe, Avinash Nivritti; Singh, Harjit; Gabata, Toshifumi; Chan, Angus C. W.; Lau, Wan Yee; Fan, Sheung Tat; Chen, Miin-Fu; Ker, Chen-Guo; Yoon, Yoo-Seok; Choi, In-Seok; Kim, Myung-Hwan; Yoon, Dong-Sup; Kitano, Seigo; Inomata, Masafumi; Hirata, Koichi; Inui, Kazuo; Sumiyama, Yoshinobu; Yamamoto, Masakazu

2018-01-01

Management bundles that define items or procedures strongly recommended in clinical practice have been used in many guidelines in recent years. Application of these bundles facilitates the adaptation of guidelines and helps improve the prognosis of target diseases. In Tokyo Guidelines 2013 (TG13),

HSPB1 facilitates the formation of non-centrosomal microtubules.

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Leonardo Almeida-Souza

Full Text Available The remodeling capacity of microtubules (MT is essential for their proper function. In mammals, MTs are predominantly formed at the centrosome, but can also originate from non-centrosomal sites, a process that is still poorly understood. We here show that the small heat shock protein HSPB1 plays a role in the control of non-centrosomal MT formation. The HSPB1 expression level regulates the balance between centrosomal and non-centrosomal MTs. The HSPB1 protein can be detected specifically at sites of de novo forming non-centrosomal MTs, while it is absent from the centrosomes. In addition, we show that HSPB1 binds preferentially to the lattice of newly formed MTs in vitro, suggesting that its function occurs by stabilizing MT seeds. Our findings open new avenues for the understanding of the role of HSPB1 in the development, maintenance and protection of cells with specialized non-centrosomal MT arrays.

YB-1 promotes microtubule assembly in vitro through interaction with tubulin and microtubules

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Baconnais Sonia

2008-09-01

Full Text Available Abstract Background YB-1 is a major regulator of gene expression in eukaryotic cells. In addition to its role in transcription, YB-1 plays a key role in translation and stabilization of mRNAs. Results We show here that YB-1 interacts with tubulin and microtubules and stimulates microtubule assembly in vitro. High resolution imaging via electron and atomic force microscopy revealed that microtubules assembled in the presence of YB-1 exhibited a normal single wall ultrastructure and indicated that YB-1 most probably coats the outer microtubule wall. Furthermore, we found that YB-1 also promotes the assembly of MAPs-tubulin and subtilisin-treated tubulin. Finally, we demonstrated that tubulin interferes with RNA:YB-1 complexes. Conclusion These results suggest that YB-1 may regulate microtubule assembly in vivo and that its interaction with tubulin may contribute to the control of mRNA translation.

Microtubule nucleation and organization in dendrites

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Delandre, Caroline; Amikura, Reiko; Moore, Adrian W.

2016-01-01

ABSTRACT Dendrite branching is an essential process for building complex nervous systems. It determines the number, distribution and integration of inputs into a neuron, and is regulated to create the diverse dendrite arbor branching patterns characteristic of different neuron types. The microtubule cytoskeleton is critical to provide structure and exert force during dendrite branching. It also supports the functional requirements of dendrites, reflected by differential microtubule architectural organization between neuron types, illustrated here for sensory neurons. Both anterograde and retrograde microtubule polymerization occur within growing dendrites, and recent studies indicate that branching is enhanced by anterograde microtubule polymerization events in nascent branches. The polarities of microtubule polymerization events are regulated by the position and orientation of microtubule nucleation events in the dendrite arbor. Golgi outposts are a primary microtubule nucleation center in dendrites and share common nucleation machinery with the centrosome. In addition, pre-existing dendrite microtubules may act as nucleation sites. We discuss how balancing the activities of distinct nucleation machineries within the growing dendrite can alter microtubule polymerization polarity and dendrite branching, and how regulating this balance can generate neuron type-specific morphologies. PMID:27097122

Manipulation and quantification of microtubule lattice integrity

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Taylor A. Reid

2017-08-01

Full Text Available Microtubules are structural polymers that participate in a wide range of cellular functions. The addition and loss of tubulin subunits allows the microtubule to grow and shorten, as well as to develop and repair defects and gaps in its cylindrical lattice. These lattice defects act to modulate the interactions of microtubules with molecular motors and other microtubule-associated proteins. Therefore, tools to control and measure microtubule lattice structure will be invaluable for developing a quantitative understanding of how the structural state of the microtubule lattice may regulate its interactions with other proteins. In this work, we manipulated the lattice integrity of in vitro microtubules to create pools of microtubules with common nucleotide states, but with variations in structural states. We then developed a series of novel semi-automated analysis tools for both fluorescence and electron microscopy experiments to quantify the type and severity of alterations in microtubule lattice integrity. These techniques will enable new investigations that explore the role of microtubule lattice structure in interactions with microtubule-associated proteins.

Near-atomic model of microtubule-tau interactions.

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Kellogg, Elizabeth H; Hejab, Nisreen M A; Poepsel, Simon; Downing, Kenneth H; DiMaio, Frank; Nogales, Eva

2018-06-15

Tau is a developmentally regulated axonal protein that stabilizes and bundles microtubules (MTs). Its hyperphosphorylation is thought to cause detachment from MTs and subsequent aggregation into fibrils implicated in Alzheimer's disease. It is unclear which tau residues are crucial for tau-MT interactions, where tau binds on MTs, and how it stabilizes them. We used cryo-electron microscopy to visualize different tau constructs on MTs and computational approaches to generate atomic models of tau-tubulin interactions. The conserved tubulin-binding repeats within tau adopt similar extended structures along the crest of the protofilament, stabilizing the interface between tubulin dimers. Our structures explain the effect of phosphorylation on MT affinity and lead to a model of tau repeats binding in tandem along protofilaments, tethering together tubulin dimers and stabilizing polymerization interfaces. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Microtubules as mechanical force sensors.

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Karafyllidis, Ioannis G; Lagoudas, Dimitris C

2007-03-01

Microtubules are polymers of tubulin subunits (dimers) arranged on a hexagonal lattice. Each tubulin dimer comprises two monomers, the alpha-tubulin and beta-tubulin, and can be found in two states. In the first state a mobile negative charge is located into the alpha-tubulin monomer and in the second into the beta-tubulin monomer. Each tubulin dimer is modeled as an electrical dipole coupled to its neighbors by electrostatic forces. The location of the mobile charge in each dimer depends on the location of the charges in the dimer's neighborhood. Mechanical forces that act on the microtubule affect the distances between the dimers and alter the electrostatic potential. Changes in this potential affect the mobile negative charge location in each dimer and the charge distribution in the microtubule. The net effect is that mechanical forces affect the charge distribution in microtubules. We propose to exploit this effect and use microtubules as mechanical force sensors. We model each dimer as a two-state quantum system and, following the quantum computation paradigm, we use discrete quantum random walk on the hexagonal microtubule lattice to determine the charge distribution. Different forces applied on the microtubule are modeled as different coin biases leading to different probability distributions of the quantum walker location, which are directly connected to different charge distributions. Simulation results show that there is a strong indication that microtubules can be used as mechanical force sensors and that they can also detect the force directions and magnitudes.

Microtubule array reorientation in response to hormones does not involve changes in microtubule nucleation modes at the periclinal cell surface

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Atkinson, Samantha; Kirik, Angela; Kirik, Viktor

2014-01-01

Aligned microtubule arrays spatially organize cell division, trafficking, and determine the direction of cell expansion in plant cells. In response to changes in environmental and developmental signals, cells reorganize their microtubule arrays into new configurations. Here, we tested the role of microtubule nucleation during hormone-induced microtubule array reorientation. We have found that in the process of microtubule array reorientation the ratios between branching, parallel, and de-novo nucleations remained constant, suggesting that the microtubule reorientation mechanism does not involve changes in nucleation modes. In the ton2/fass mutant, which has reduced microtubule branching nucleation frequency and decreased nucleation activity of the γ-tubulin complexes, microtubule arrays were able to reorient. Presented data suggest that reorientation of microtubules into transverse arrays in response to hormones does not involve changes in microtubule nucleation at the periclinal cell surface PMID:25135522

Synchronous Oscillations in Microtubule Polymerization

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Carlier, M. F.; Melki, R.; Pantaloni, D.; Hill, T. L.; Chen, Y.

1987-08-01

Under conditions where microtubule nucleation and growth are fast (i.e., high magnesium ion and tubulin concentrations and absence of glycerol), microtubule assembly in vitro exhibits an oscillatory regime preceding the establishment of steady state. The amplitude of the oscillations can represent >50% of the maximum turbidity change and oscillations persist for up to 20 periods of 80 s each. Oscillations are accompanied by extensive length redistribution of microtubules. Preliminary work suggests that the oscillatory kinetics can be simulated using a model in which many microtubules undergo synchronous transitions between growing and rapidly depolymerizing phases, complicated by the kinetically limiting rate of nucleotide exchange on free tubulin.

Assembly and control of large microtubule complexes

Science.gov (United States)

Korolev, Kirill; Ishihara, Keisuke; Mitchison, Timothy

Motility, division, and other cellular processes require rapid assembly and disassembly of microtubule structures. We report a new mechanism for the formation of asters, radial microtubule complexes found in very large cells. The standard model of aster growth assumes elongation of a fixed number of microtubules originating from the centrosomes. However, aster morphology in this model does not scale with cell size, and we found evidence for microtubule nucleation away from centrosomes. By combining polymerization dynamics and auto-catalytic nucleation of microtubules, we developed a new biophysical model of aster growth. The model predicts an explosive transition from an aster with a steady-state radius to one that expands as a travelling wave. At the transition, microtubule density increases continuously, but aster growth rate discontinuously jumps to a nonzero value. We tested our model with biochemical perturbations in egg extract and confirmed main theoretical predictions including the jump in the growth rate. Our results show that asters can grow even though individual microtubules are short and unstable. The dynamic balance between microtubule collapse and nucleation could be a general framework for the assembly and control of large microtubule complexes. NIH GM39565; Simons Foundation 409704; Honjo International 486 Scholarship Foundation.

A Mechanism for Cytoplasmic Streaming: Kinesin-Driven Alignment of Microtubules and Fast Fluid Flows.

Science.gov (United States)

Monteith, Corey E; Brunner, Matthew E; Djagaeva, Inna; Bielecki, Anthony M; Deutsch, Joshua M; Saxton, William M

2016-05-10

The transport of cytoplasmic components can be profoundly affected by hydrodynamics. Cytoplasmic streaming in Drosophila oocytes offers a striking example. Forces on fluid from kinesin-1 are initially directed by a disordered meshwork of microtubules, generating minor slow cytoplasmic flows. Subsequently, to mix incoming nurse cell cytoplasm with ooplasm, a subcortical layer of microtubules forms parallel arrays that support long-range, fast flows. To analyze the streaming mechanism, we combined observations of microtubule and organelle motions with detailed mathematical modeling. In the fast state, microtubules tethered to the cortex form a thin subcortical layer and undergo correlated sinusoidal bending. Organelles moving in flows along the arrays show velocities that are slow near the cortex and fast on the inward side of the subcortical microtubule layer. Starting with fundamental physical principles suggested by qualitative hypotheses, and with published values for microtubule stiffness, kinesin velocity, and cytoplasmic viscosity, we developed a quantitative coupled hydrodynamic model for streaming. The fully detailed mathematical model and its simulations identify key variables that can shift the system between disordered (slow) and ordered (fast) states. Measurements of array curvature, wave period, and the effects of diminished kinesin velocity on flow rates, as well as prior observations on f-actin perturbation, support the model. This establishes a concrete mechanistic framework for the ooplasmic streaming process. The self-organizing fast phase is a result of viscous drag on kinesin-driven cargoes that mediates equal and opposite forces on cytoplasmic fluid and on microtubules whose minus ends are tethered to the cortex. Fluid moves toward plus ends and microtubules are forced backward toward their minus ends, resulting in buckling. Under certain conditions, the buckling microtubules self-organize into parallel bending arrays, guiding varying directions

Microtubules self-repair in response to mechanical stress

Science.gov (United States)

Schaedel, Laura; John, Karin; Gaillard, Jérémie; Nachury, Maxence V.; Blanchoin, Laurent; Théry, Manuel

2015-11-01

Microtubules--which define the shape of axons, cilia and flagella, and provide tracks for intracellular transport--can be highly bent by intracellular forces, and microtubule structure and stiffness are thought to be affected by physical constraints. Yet how microtubules tolerate the vast forces exerted on them remains unknown. Here, by using a microfluidic device, we show that microtubule stiffness decreases incrementally with each cycle of bending and release. Similar to other cases of material fatigue, the concentration of mechanical stresses on pre-existing defects in the microtubule lattice is responsible for the generation of more extensive damage, which further decreases microtubule stiffness. Strikingly, damaged microtubules were able to incorporate new tubulin dimers into their lattice and recover their initial stiffness. Our findings demonstrate that microtubules are ductile materials with self-healing properties, that their dynamics does not exclusively occur at their ends, and that their lattice plasticity enables the microtubules' adaptation to mechanical stresses.

Mechanics of microtubules: effects of protofilament orientation.

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Donhauser, Zachary J; Jobs, William B; Binka, Edem C

2010-09-08

Microtubules are hollow cylindrical polymers of the protein tubulin that play a number of important dynamic and structural roles in eukaryotic cells. Both in vivo and in vitro microtubules can exist in several possible configurations, differing in the number of protofilaments, helical rise of tubulin dimers, and protofilament skew angle with respect to the main tube axis. Here, finite element modeling is applied to examine the mechanical response of several known microtubule types when subjected to radial deformation. The data presented here provide an important insight into microtubule stiffness and reveal that protofilament orientation does not affect radial stiffness. Rather, stiffness is primarily dependent on the effective Young's modulus of the polymerized material and the effective radius of the microtubule. These results are also directly correlated to atomic force microscopy nanoindentation measurements to allow a more detailed interpretation of previous experiments. When combined with experimental data that show a significant difference between microtubules stabilized with a slowly hydrolyzable GTP analog and microtubules stabilized with paclitaxel, the finite element data suggest that paclitaxel increases the overall radial flexibility of the microtubule wall. Copyright 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Microtubules Growth Rate Alteration in Human Endothelial Cells

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Irina B. Alieva

2010-01-01

Full Text Available To understand how microtubules contribute to the dynamic reorganization of the endothelial cell (EC cytoskeleton, we established an EC model expressing EB3-GFP, a protein that marks microtubule plus-ends. Using this model, we were able to measure microtubule growth rate at the centrosome region and near the cell periphery of a single human EC and in the EC monolayer. We demonstrate that the majority of microtubules in EC are dynamic, the growth rate of their plus-ends is highest in the internal cytoplasm, in the region of the centrosome. Growth rate of microtubule plus-ends decreases from the cell center toward the periphery. Our data suggest the existing mechanism(s of local regulation of microtubule plus-ends growth in EC. Microtubule growth rate in the internal cytoplasm of EC in the monolayer is lower than that of single EC suggesting the regulatory effect of cell-cell contacts. Centrosomal microtubule growth rate distribution in single EC indicated the presence of two subpopulations of microtubules with “normal” (similar to those in monolayer EC and “fast” (three times as much growth rates. Our results indicate functional interactions between cell-cell contacts and microtubules.

GDP-tubulin incorporation into growing microtubules modulates polymer stability.

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Valiron, Odile; Arnal, Isabelle; Caudron, Nicolas; Job, Didier

2010-06-04

Microtubule growth proceeds through the endwise addition of nucleotide-bound tubulin dimers. The microtubule wall is composed of GDP-tubulin subunits, which are thought to come exclusively from the incorporation of GTP-tubulin complexes at microtubule ends followed by GTP hydrolysis within the polymer. The possibility of a direct GDP-tubulin incorporation into growing polymers is regarded as hardly compatible with recent structural data. Here, we have examined GTP-tubulin and GDP-tubulin incorporation into polymerizing microtubules using a minimal assembly system comprised of nucleotide-bound tubulin dimers, in the absence of free nucleotide. We find that GDP-tubulin complexes can efficiently co-polymerize with GTP-tubulin complexes during microtubule assembly. GDP-tubulin incorporation into microtubules occurs with similar efficiency during bulk microtubule assembly as during microtubule growth from seeds or centrosomes. Microtubules formed from GTP-tubulin/GDP-tubulin mixtures display altered microtubule dynamics, in particular a decreased shrinkage rate, apparently due to intrinsic modifications of the polymer disassembly properties. Thus, although microtubules polymerized from GTP-tubulin/GDP-tubulin mixtures or from homogeneous GTP-tubulin solutions are both composed of GDP-tubulin subunits, they have different dynamic properties, and this may reveal a novel form of microtubule "structural plasticity."

Variable recruitment in bundles of miniature pneumatic artificial muscles.

Science.gov (United States)

DeLaHunt, Sylvie A; Pillsbury, Thomas E; Wereley, Norman M

2016-09-13

The natural compliance and force generation properties of pneumatic artificial muscles (PAMs) allow them to operate like human muscles in anthropomorphic robotic manipulators. Traditionally, manipulators use a single PAM or multiple PAMs actuated in unison in place of a human muscle. However, these standard manipulators can experience significant efficiency losses when operated outside their target performance ranges at low actuation pressures. This study considers the application of a variable recruitment control strategy to a parallel bundle of miniature PAMs as an attempt to mimic the selective recruitment of motor units in a human muscle. Bundles of miniature PAMs are experimentally characterized, their actuation behavior is modeled, and the efficiency gains and losses associated with the application of a variable recruitment control strategy are assessed. This bio-inspired control strategy allows muscle bundles to operate the fewest miniature PAMs necessary to achieve a desired performance objective, improving the muscle bundle's operating efficiency over larger ranges of force generation and displacement. The study also highlights the need for improved PAM fabrication techniques to facilitate the production of identical miniature PAMs for inclusion in muscle bundles.

Understanding nurses' views on a pressure ulcer prevention care bundle: a first step towards successful implementation.

Science.gov (United States)

Chaboyer, Wendy; Gillespie, Brigid M

2014-12-01

To explore nurses' views of the barriers and facilitators to the use of a newly devised patient-centred pressure ulcer prevention care bundle. Given pressure ulcer prevention strategies are not implemented consistently, the use of a pressure ulcer care bundle may improve implementation given bundles generally assist in standardising care. A quality improvement project was undertaken after a pressure ulcer prevention care bundle was developed and pilot-tested. Short, conversational interviews with nurse explored their views of a patient-centred pressure ulcer care bundle. Interviews were audio-taped and transcribed. Inductive content analysis was used to analyse the transcripts. A total of 20 nurses were interviewed. Five categories with corresponding subcategories emerged from the analysis. They were increasing awareness of pressure ulcer prevention, prompting pressure ulcer prevention activities, promoting active patient participation, barriers to using a pressure ulcer prevention care bundle and enabling integration of the pressure ulcer prevention care bundle into routine practice. Benefits of using a patient-centred pressure ulcer prevention care bundle may include prompting patients and staff to implement prevention strategies and promote active patient participation in care. The success of the care bundle relied on both patients' willingness to participate and nurses' willingness to incorporate it into their routine work. A patient-centred pressure ulcer prevention care bundle may facilitate more consistent implementation of pressure ulcer prevention strategies and active patient participation in care. © 2014 John Wiley & Sons Ltd.

A novel approach to leveraging electronic health record data to enhance pediatric surgical quality improvement bundle process compliance.

Science.gov (United States)

Fisher, Jason C; Godfried, David H; Lighter-Fisher, Jennifer; Pratko, Joseph; Sheldon, Mary Ellen; Diago, Thelma; Kuenzler, Keith A; Tomita, Sandra S; Ginsburg, Howard B

2016-06-01

Quality improvement (QI) bundles have been widely adopted to reduce surgical site infections (SSI). Improvement science suggests when organizations achieve high-reliability to QI processes, outcomes dramatically improve. However, measuring QI process compliance is poorly supported by electronic health record (EHR) systems. We developed a custom EHR tool to facilitate capture of process data for SSI prevention with the aim of increasing bundle compliance and reducing adverse events. Ten SSI prevention bundle processes were linked to EHR data elements that were then aggregated into a snapshot display superimposed on weekly case-log reports. The data aggregation and user interface facilitated efficient review of all SSI bundle elements, providing an exact bundle compliance rate without random sampling or chart review. Nine months after implementation of our custom EHR tool, we observed centerline shifts in median SSI bundle compliance (46% to 72%). Additionally, as predicted by high reliability principles, we began to see a trend toward improvement in SSI rates (1.68 to 0.87 per 100 operations), but a discrete centerline shift was not detected. Simple informatics solutions can facilitate extraction of QI process data from the EHR without relying on adjunctive systems. Analyses of these data may drive reductions in adverse events. Pediatric surgical departments should consider leveraging the EHR to enhance bundle compliance as they implement QI strategies. Copyright © 2016 Elsevier Inc. All rights reserved.

Phosphatase PP2A and microtubule-mediated pulling forces disassemble centrosomes during mitotic exit

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Stephen J. Enos

2018-01-01

Full Text Available Centrosomes are microtubule-nucleating organelles that facilitate chromosome segregation and cell division in metazoans. Centrosomes comprise centrioles that organize a micron-scale mass of protein called pericentriolar material (PCM from which microtubules nucleate. During each cell cycle, PCM accumulates around centrioles through phosphorylation-mediated assembly of PCM scaffold proteins. During mitotic exit, PCM swiftly disassembles by an unknown mechanism. Here, we used Caenorhabditis elegans embryos to determine the mechanism and importance of PCM disassembly in dividing cells. We found that the phosphatase PP2A and its regulatory subunit SUR-6 (PP2ASUR-6, together with cortically directed microtubule pulling forces, actively disassemble PCM. In embryos depleted of these activities, ∼25% of PCM persisted from one cell cycle into the next. Purified PP2ASUR-6 could dephosphorylate the major PCM scaffold protein SPD-5 in vitro. Our data suggest that PCM disassembly occurs through a combination of dephosphorylation of PCM components and force-driven fragmentation of the PCM scaffold.

Effects of the KIF2C neck peptide on microtubules: lateral disintegration of microtubules and β-structure formation.

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Shimizu, Youské; Shimizu, Takashi; Nara, Masayuki; Kikumoto, Mahito; Kojima, Hiroaki; Morii, Hisayuki

2013-04-01

Members of the kinesin-13 sub-family, including KIF2C, depolymerize microtubules. The positive charge-rich 'neck' region extending from the N-terminus of the catalytic head is considered to be important in the depolymerization activity. Chemically synthesized peptides, covering the basic region (A182-E200), induced a sigmoidal increase in the turbidity of a microtubule suspension. The increase was suppressed by salt addition or by reduction of basicity by amino acid substitutions. Electron microscopic observations revealed ring structures surrounding the microtubules at high peptide concentrations. Using the peptide A182-D218, we also detected free thin straight filaments, probably protofilaments disintegrated from microtubules. Therefore, the neck region, even without the catalytic head domain, may induce lateral disintegration of microtubules. With microtubules lacking anion-rich C-termini as a result of subtilisin treatment, addition of the peptide induced only a moderate increase in turbidity, and rings and protofilaments were rarely detected, while aggregations, also thought to be caused by lateral disintegration, were often observed in electron micrographs. Thus, the C-termini are not crucial for the action of the peptides in lateral disintegration but contribute to structural stabilization of the protofilaments. Previous structural studies indicated that the neck region of KIF2C is flexible, but our IR analysis suggests that the cation-rich region (K190-A204) forms β-structure in the presence of microtubules, which may be of significance with regard to the action of the neck region. Therefore, the neck region of KIF2C is sufficient to cause disintegration of microtubules into protofilaments, and this may contribute to the ability of KIF2C to cause depolymerization of microtubules. © 2013 The Authors Journal compilation © 2013 FEBS.

KATNAL1 regulation of sertoli cell microtubule dynamics is essential for spermiogenesis and male fertility.

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Lee B Smith

Full Text Available Spermatogenesis is a complex process reliant upon interactions between germ cells (GC and supporting somatic cells. Testicular Sertoli cells (SC support GCs during maturation through physical attachment, the provision of nutrients, and protection from immunological attack. This role is facilitated by an active cytoskeleton of parallel microtubule arrays that permit transport of nutrients to GCs, as well as translocation of spermatids through the seminiferous epithelium during maturation. It is well established that chemical perturbation of SC microtubule remodelling leads to premature GC exfoliation demonstrating that microtubule remodelling is an essential component of male fertility, yet the genes responsible for this process remain unknown. Using a random ENU mutagenesis approach, we have identified a novel mouse line displaying male-specific infertility, due to a point mutation in the highly conserved ATPase domain of the novel KATANIN p60-related microtubule severing protein Katanin p60 subunit A-like1 (KATNAL1. We demonstrate that Katnal1 is expressed in testicular Sertoli cells (SC from 15.5 days post-coitum (dpc and that, consistent with chemical disruption models, loss of function of KATNAL1 leads to male-specific infertility through disruption of SC microtubule dynamics and premature exfoliation of spermatids from the seminiferous epithelium. The identification of KATNAL1 as an essential regulator of male fertility provides a significant novel entry point into advancing our understanding of how SC microtubule dynamics promotes male fertility. Such information will have resonance both for future treatment of male fertility and the development of non-hormonal male contraceptives.

Nerve growth factor stimulates axon outgrowth through negative regulation of growth cone actomyosin restraint of microtubule advance.

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Turney, Stephen G; Ahmed, Mostafa; Chandrasekar, Indra; Wysolmerski, Robert B; Goeckeler, Zoe M; Rioux, Robert M; Whitesides, George M; Bridgman, Paul C

2016-02-01

Nerve growth factor (NGF) promotes growth, differentiation, and survival of sensory neurons in the mammalian nervous system. Little is known about how NGF elicits faster axon outgrowth or how growth cones integrate and transform signal input to motor output. Using cultured mouse dorsal root ganglion neurons, we found that myosin II (MII) is required for NGF to stimulate faster axon outgrowth. From experiments inducing loss or gain of function of MII, specific MII isoforms, and vinculin-dependent adhesion-cytoskeletal coupling, we determined that NGF causes decreased vinculin-dependent actomyosin restraint of microtubule advance. Inhibition of MII blocked NGF stimulation, indicating the central role of restraint in directed outgrowth. The restraint consists of myosin IIB- and IIA-dependent processes: retrograde actin network flow and transverse actin bundling, respectively. The processes differentially contribute on laminin-1 and fibronectin due to selective actin tethering to adhesions. On laminin-1, NGF induced greater vinculin-dependent adhesion-cytoskeletal coupling, which slowed retrograde actin network flow (i.e., it regulated the molecular clutch). On fibronectin, NGF caused inactivation of myosin IIA, which negatively regulated actin bundling. On both substrates, the result was the same: NGF-induced weakening of MII-dependent restraint led to dynamic microtubules entering the actin-rich periphery more frequently, giving rise to faster elongation. © 2016 Turney 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).

Centriolar CPAP/SAS-4 Imparts Slow Processive Microtubule Growth

NARCIS (Netherlands)

Sharma, Ashwani; Aher, Amol; Dynes, Nicola J; Frey, Daniel; Katrukha, Eugene A; Jaussi, Rolf; Grigoriev, Ilya; Croisier, Marie; Kammerer, Richard A; Akhmanova, Anna; Gönczy, Pierre; Steinmetz, Michel O

2016-01-01

Centrioles are fundamental and evolutionarily conserved microtubule-based organelles whose assembly is characterized by microtubule growth rates that are orders of magnitude slower than those of cytoplasmic microtubules. Several centriolar proteins can interact with tubulin or microtubules, but how

Microtubules become more dynamic but not shorter during preprophase band formation: A possible "search-and-capture" mechanism for microtubule translocation

NARCIS (Netherlands)

Vos, J.W.; Dogterom, M.; Emons, A.M.C.

2004-01-01

The dynamic behavior of the microtubule cytoskeleton plays a crucial role in cellular organization, but the physical mechanisms underlying microtubule (re)organization in plant cells are poorly understood. We investigated microtubule dynamics in tobacco BY-2 suspension cells during interphase and

Simulation of finite size effects of the fiber bundle model

Science.gov (United States)

Hao, Da-Peng; Tang, Gang; Xun, Zhi-Peng; Xia, Hui; Han, Kui

2018-01-01

In theory, the macroscopic fracture of materials should correspond with the thermodynamic limit of the fiber bundle model. However, the simulation of a fiber bundle model with an infinite size is unrealistic. To study the finite size effects of the fiber bundle model, fiber bundle models of various size are simulated in detail. The effects of system size on the constitutive behavior, critical stress, maximum avalanche size, avalanche size distribution, and increased step number of external load are explored. The simulation results imply that there is no feature size or cut size for macroscopic mechanical and statistical properties of the model. The constitutive curves near the macroscopic failure for various system size can collapse well with a simple scaling relationship. Simultaneously, the introduction of a simple extrapolation method facilitates the acquisition of more accurate simulation results in a large-limit system, which is better for comparison with theoretical results.

The Microtubule Regulatory Protein Stathmin Is Required to Maintain the Integrity of Axonal Microtubules in Drosophila

Science.gov (United States)

Duncan, Jason E.; Lytle, Nikki K.; Zuniga, Alfredo; Goldstein, Lawrence S. B.

2013-01-01

Axonal transport, a form of long-distance, bi-directional intracellular transport that occurs between the cell body and synaptic terminal, is critical in maintaining the function and viability of neurons. We have identified a requirement for the stathmin (stai) gene in the maintenance of axonal microtubules and regulation of axonal transport in Drosophila . The stai gene encodes a cytosolic phosphoprotein that regulates microtubule dynamics by partitioning tubulin dimers between pools of soluble tubulin and polymerized microtubules, and by directly binding to microtubules and promoting depolymerization. Analysis of stai function in Drosophila , which has a single stai gene, circumvents potential complications with studies performed in vertebrate systems in which mutant phenotypes may be compensated by genetic redundancy of other members of the stai gene family. This has allowed us to identify an essential function for stai in the maintenance of the integrity of axonal microtubules. In addition to the severe disruption in the abundance and architecture of microtubules in the axons of stai mutant Drosophila , we also observe additional neurological phenotypes associated with loss of stai function including a posterior paralysis and tail-flip phenotype in third instar larvae, aberrant accumulation of transported membranous organelles in stai deficient axons, a progressive bang-sensitive response to mechanical stimulation reminiscent of the class of Drosophila mutants used to model human epileptic seizures, and a reduced adult lifespan. Reductions in the levels of Kinesin-1, the primary anterograde motor in axonal transport, enhance these phenotypes. Collectively, our results indicate that stai has an important role in neuronal function, likely through the maintenance of microtubule integrity in the axons of nerves of the peripheral nervous system necessary to support and sustain long-distance axonal transport. PMID:23840848

Heterotic line bundle models on elliptically fibered Calabi-Yau three-folds

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Braun, Andreas P.; Brodie, Callum R.; Lukas, Andre

2018-04-01

We analyze heterotic line bundle models on elliptically fibered Calabi-Yau three-folds over weak Fano bases. In order to facilitate Wilson line breaking to the standard model group, we focus on elliptically fibered three-folds with a second section and a freely-acting involution. Specifically, we consider toric weak Fano surfaces as base manifolds and identify six such manifolds with the required properties. The requisite mathematical tools for the construction of line bundle models on these spaces, including the calculation of line bundle cohomology, are developed. A computer scan leads to more than 400 line bundle models with the right number of families and an SU(5) GUT group which could descend to standard-like models after taking the ℤ2 quotient. A common and surprising feature of these models is the presence of a large number of vector-like states.

Higher order jet prolongations type gauge natural bundles over vector bundles

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Jan Kurek

2004-05-01

Full Text Available Let $rgeq 3$ and $mgeq 2$ be natural numbers and $E$ be a vector bundle with $m$-dimensional basis. We find all gauge natural bundles ``similar" to the $r$-jet prolongation bundle $J^rE$ of $E$. We also find all gauge natural bundles ``similar" to the vector $r$-tangent bundle $(J^r_{fl}(E,R_0^*$ of $E$.

Producing Conditional Mutants for Studying Plant Microtubule Function

Energy Technology Data Exchange (ETDEWEB)

Richard Cyr

2009-09-29

The cytoskeleton, and in particular its microtubule component, participates in several processes that directly affect growth and development in higher plants. Normal cytoskeletal function requires the precise and orderly arrangement of microtubules into several cell cycle and developmentally specific arrays. One of these, the cortical array, is notable for its role in directing the deposition of cellulose (the most prominent polymer in the biosphere). An understanding of how these arrays form, and the molecular interactions that contribute to their function, is incomplete. To gain a better understanding of how microtubules work, we have been working to characterize mutants in critical cytoskeletal genes. This characterization is being carried out at the subcellular level using vital microtubule gene constructs. In the last year of funding colleagues have discovered that gamma-tubulin complexes form along the lengths of cortical microtubules where they act to spawn new microtubules at a characteristic 40 deg angle. This finding complements nicely the finding from our lab (which was funded by the DOE) showing that microtubule encounters are angle dependent; high angles encounters results in catastrophic collisions while low angle encounters result in favorable zippering. The finding of a 40 deg spawn of new microtubules from extant microtubule, together with aforementioned rules of encounters, insures favorable co-alignment in the array. I was invited to write a New and Views essay on this topic and a PDF is attached (News and Views policy does not permit funding acknowledgments and so I was not allowed to acknowledge support from the DOE).

The Role of Molecular Microtubule Motors and the Microtubule Cytoskeleton in Stress Granule Dynamics

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Kristen M. Bartoli

2011-01-01

Full Text Available Stress granules (SGs are cytoplasmic foci that appear in cells exposed to stress-induced translational inhibition. SGs function as a triage center, where mRNAs are sorted for storage, degradation, and translation reinitiation. The underlying mechanisms of SGs dynamics are still being characterized, although many key players have been identified. The main components of SGs are stalled 48S preinitiation complexes. To date, many other proteins have also been found to localize in SGs and are hypothesized to function in SG dynamics. Most recently, the microtubule cytoskeleton and associated motor proteins have been demonstrated to function in SG dynamics. In this paper, we will discuss current literature examining the function of microtubules and the molecular microtubule motors in SG assembly, coalescence, movement, composition, organization, and disassembly.

Project JOINTS: what factors affect bundle adoption in a voluntary quality improvement campaign?

Science.gov (United States)

Khodyakov, Dmitry; Ridgely, M Susan; Huang, Christina; DeBartolo, Katherine O; Sorbero, Melony E; Schneider, Eric C

2015-01-01

Diffusion and adoption of effective evidence-based clinical practices can be slow, especially if complex changes are required to implement new practices. To examine how hospital adherence to quality improvement (QI) methods and hospital engagement with a large-scale QI campaign could facilitate the adoption of an enhanced prevention bundle designed to reduce surgical site infection (SSI) rates after orthopaedic surgery (hip and knee arthroplasty). We conducted telephone interviews with hospital QI leaders from 73 of the 109 hospitals (67% response rate) in five states that participated in Project JOINTS (Joining Organizations IN Tackling SSIs), a QI campaign run by Institute for Healthcare Improvement (IHI). Using QI methods grounded in the IHI Model for Improvement, this campaign encouraged hospitals to implement an enhanced SSI prevention bundle. Hospital QI leaders reported on their hospital's adherence to the Project JOINTS QI methods; their level of engagement with Project JOINTS activities; and adoption of the SSI prevention bundle components. Interview data were analysed quantitatively and qualitatively. Both adherence to the QI methods and hospital engagement were positively associated with complete bundle adoption. Hospital engagement, especially the use of project materials and tools, was also positively associated with the initiation of and improved adherence to individual bundle components. Our findings suggest that greater adherence to the QI methods and active hospital engagement in a QI campaign facilitate adoption of evidence-based patient safety bundles in orthopaedic practice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Biological Information Processing in Single Microtubules

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2014-03-05

generated by synchronized oscillations of microtubules, centrosomes and chromosomes regulate the dynamics of mitosis and meiosis, Yue Zhao and Qimin...of frequency by a single microtubule. Green arrows depict the peaks that appear in absorption and disappear in transmission. Purple arrows show

S. pombe kinesins-8 promote both nucleation and catastrophe of microtubules.

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Muriel Erent

Full Text Available The kinesins-8 were originally thought to be microtubule depolymerases, but are now emerging as more versatile catalysts of microtubule dynamics. We show here that S. pombe Klp5-436 and Klp6-440 are non-processive plus-end-directed motors whose in vitro velocities on S. pombe microtubules at 7 and 23 nm s(-1 are too slow to keep pace with the growing tips of dynamic interphase microtubules in living S. pombe. In vitro, Klp5 and 6 dimers exhibit a hitherto-undescribed combination of strong enhancement of microtubule nucleation with no effect on growth rate or catastrophe frequency. By contrast in vivo, both Klp5 and Klp6 promote microtubule catastrophe at cell ends whilst Klp6 also increases the number of interphase microtubule arrays (IMAs. Our data support a model in which Klp5/6 bind tightly to free tubulin heterodimers, strongly promoting the nucleation of new microtubules, and then continue to land as a tubulin-motor complex on the tips of growing microtubules, with the motors then dissociating after a few seconds residence on the lattice. In vivo, we predict that only at cell ends, when growing microtubule tips become lodged and their growth slows down, will Klp5/6 motor activity succeed in tracking growing microtubule tips. This mechanism would allow Klp5/6 to detect the arrival of microtubule tips at cells ends and to amplify the intrinsic tendency for microtubules to catastrophise in compression at cell ends. Our evidence identifies Klp5 and 6 as spatial regulators of microtubule dynamics that enhance both microtubule nucleation at the cell centre and microtubule catastrophe at the cell ends.

Centrosome and microtubule instability in aging Drosophila cells

Science.gov (United States)

Schatten, H.; Chakrabarti, A.; Hedrick, J.

1999-01-01

Several cytoskeletal changes are associated with aging which includes alterations in muscle structure leading to muscular atrophy, and weakening of the microtubule network which affects cellular secretion and maintenance of cell shape. Weakening of the microtubule network during meiosis in aging oocytes can result in aneuploidy or trisomic zygotes with increasing maternal age. Imbalances of cytoskeletal organization can lead to disease such as Alzheimer's, muscular disorders, and cancer. Because many cytoskeletal diseases are related to age we investigated the effects of aging on microtubule organization in cell cultures of the Drosophila cell model system (Schneider S-1 and Kc23 cell lines). This cell model is increasingly being used as an alternative system to mammalian cell cultures. Drosophila cells are amenable to genetic manipulations and can be used to identify and manipulate genes which are involved in the aging processes. Immunofluorescence, scanning, and transmission electron microscopy were employed for the analysis of microtubule organizing centers (centrosomes) and microtubules at various times after subculturing cells in fresh medium. Our results reveal that centrosomes and the microtubule network becomes significantly affected in aging cells after 5 days of subculture. At 5-14 days of subculture, 1% abnormal out of 3% mitoses were noted which were clearly distinguishable from freshly subcultured control cells in which 3% of cells undergo normal mitosis with bipolar configurations. Microtubules are also affected in the midbody during cell division. The midbody in aging cells becomes up to 10 times longer when compared with midbodies in freshly subcultured cells. During interphase, microtubules are often disrupted and disorganized, which may indicate improper function related to transport of cell organelles along microtubules. These results are likely to help explain some cytoskeletal disorders and diseases related to aging.

The Drosophila Microtubule-Associated Protein Mars Stabilizes Mitotic Spindles by Crosslinking Microtubules through Its N-Terminal Region

DEFF Research Database (Denmark)

Zhang, Gang; Beati, Hamze; Nilsson, Jakob

2013-01-01

Correct segregation of genetic material relies on proper assembly and maintenance of the mitotic spindle. How the highly dynamic microtubules (MTs) are maintained in stable mitotic spindles is a key question to be answered. Motor and non-motor microtubule associated proteins (MAPs) have been...

Effect of radiation on microtubule structure in cancer cells

International Nuclear Information System (INIS)

Tripath, Shambhoo Sharan; Panda, Dulal; Jayakumar, S.; Maikho, Thoh; Sandur, Santosh Kumar

2017-01-01

Microtubules (MT) are dynamic structural cellular components. In proliferating cells, they are essential components in cell division through the formation of the mitotic spindle. Radiotherapy is an integral part of cancer treatment for most of the solid cancers. Scanty data exists in the literature related to how ionizing radiation affects microtubule reorganization in tumor cells. In the present study, breast cancer cell line (MCF-7 cells) was exposed to different doses of radiation (2-10Gy). Cells were cultured for 24 h, fixed and stained with antitubulin antibody and subjected to immunofluorescence microscopy. In another experiment, cells were subjected to cold treatment for 5 min or 30 min for studying the disassembly of microtubules after 24 h of irradiation. Further, these cells were incubated at 37°C for 20 min for studying the reassembly of microtubules. Acetylation of microtubule was also examined after exposure of cells to radiation. Experiments were also performed by combining radiation with low concentration of CXI-Benzo 84 (MT destabilizing agent 1 and 2.5 uM). Exposure of MCF-7 cells to radiation lead to destabilization of microtubules. Interestingly, destabilization of microtubule was faster upon cold treatment in irradiated group as compared to control group. These cells failed to re-stabilize at 37°C. Radiation also reduced the acetylation level of microtubule. Combination treatment of CXI-Benzo 84 with radiation exhibited additive effect in terms of depolymerization of MT. Our results suggest that ionizing radiation indeed modulates microtubule dynamics. (author)

Microtubules are organized independently of the centrosome in Drosophila neurons

Directory of Open Access Journals (Sweden)

Nguyen Michelle M

2011-12-01

Full Text Available Abstract Background The best-studied arrangement of microtubules is that organized by the centrosome, a cloud of microtubule nucleating and anchoring proteins is clustered around centrioles. However, noncentrosomal microtubule arrays are common in many differentiated cells, including neurons. Although microtubules are not anchored at neuronal centrosomes, it remains unclear whether the centrosome plays a role in organizing neuronal microtubules. We use Drosophila as a model system to determine whether centrosomal microtubule nucleation is important in mature neurons. Results In developing and mature neurons, centrioles were not surrounded by the core nucleation protein γ-tubulin. This suggests that the centrioles do not organize functional centrosomes in Drosophila neurons in vivo. Consistent with this idea, centriole position was not correlated with a specific region of the cell body in neurons, and growing microtubules did not cluster around the centriole, even after axon severing when the number of growing plus ends is dramatically increased. To determine whether the centrosome was required for microtubule organization in mature neurons, we used two approaches. First, we used DSas-4 centriole duplication mutants. In these mutants, centrioles were present in many larval sensory neurons, but they were not fully functional. Despite reduced centriole function, microtubule orientation was normal in axons and dendrites. Second, we used laser ablation to eliminate the centriole, and again found that microtubule polarity in axons and dendrites was normal, even 3 days after treatment. Conclusion We conclude that the centrosome is not a major site of microtubule nucleation in Drosophila neurons, and is not required for maintenance of neuronal microtubule organization in these cells.

The Atiyah bundle and connections on a principal bundle

Indian Academy of Sciences (India)

be the fiber bundle constructed as in (1.1) for the universal principal G-bundle. In a work in progress, we hope to show that the universal G-connection can be realized as a fiber bundle over C(EG). Turning this ... a G-invariant vector field on EG|U . In other words, we get a bijective linear map between. A(EG)(U) (the space of ...

EML proteins in microtubule regulation and human disease.

Science.gov (United States)

Fry, Andrew M; O'Regan, Laura; Montgomery, Jessica; Adib, Rozita; Bayliss, Richard

2016-10-15

The EMLs are a conserved family of microtubule-associated proteins (MAPs). The founding member was discovered in sea urchins as a 77-kDa polypeptide that co-purified with microtubules. This protein, termed EMAP for echinoderm MAP, was the major non-tubulin component present in purified microtubule preparations made from unfertilized sea urchin eggs [J. Cell Sci. (1993) 104: , 445-450; J. Cell Sci. (1987) 87: (Pt 1), 71-84]. Orthologues of EMAP were subsequently identified in other echinoderms, such as starfish and sand dollar, and then in more distant eukaryotes, including flies, worms and vertebrates, where the name of ELP or EML (both for EMAP-like protein) has been adopted [BMC Dev. Biol. (2008) 8: , 110; Dev. Genes Evol. (2000) 210: , 2-10]. The common property of these proteins is their ability to decorate microtubules. However, whether they are associated with particular microtubule populations or exercise specific functions in different microtubule-dependent processes remains unknown. Furthermore, although there is limited evidence that they regulate microtubule dynamics, the biochemical mechanisms of their molecular activity have yet to be explored. Nevertheless, interest in these proteins has grown substantially because of the identification of EML mutations in neuronal disorders and oncogenic fusions in human cancers. Here, we summarize our current knowledge of the expression, localization and structure of what is proving to be an interesting and important class of MAPs. We also speculate about their function in microtubule regulation and highlight how the studies of EMLs in human diseases may open up novel avenues for patient therapy. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Designing cooperatively folded abiotic uni- and multimolecular helix bundles

Science.gov (United States)

de, Soumen; Chi, Bo; Granier, Thierry; Qi, Ting; Maurizot, Victor; Huc, Ivan

2018-01-01

Abiotic foldamers, that is foldamers that have backbones chemically remote from peptidic and nucleotidic skeletons, may give access to shapes and functions different to those of peptides and nucleotides. However, design methodologies towards abiotic tertiary and quaternary structures are yet to be developed. Here we report rationally designed interactional patterns to guide the folding and assembly of abiotic helix bundles. Computational design facilitated the introduction of hydrogen-bonding functionalities at defined locations on the aromatic amide backbones that promote cooperative folding into helix-turn-helix motifs in organic solvents. The hydrogen-bond-directed aggregation of helices not linked by a turn unit produced several thermodynamically and kinetically stable homochiral dimeric and trimeric bundles with structures that are distinct from the designed helix-turn-helix. Relative helix orientation within the bundles may be changed from parallel to tilted on subtle solvent variations. Altogether, these results prefigure the richness and uniqueness of abiotic tertiary structure behaviour.

Polyelectrolyte bundles

Energy Technology Data Exchange (ETDEWEB)

Limbach, H J; Sayar, M; Holm, C [Max-Planck-Institut fuer Polymerforschung, Ackermannweg 10, 55128 Mainz (Germany)

2004-06-09

Using extensive molecular dynamics simulations we study the behaviour of polyelectrolytes with hydrophobic side chains, which are known to form cylindrical micelles in aqueous solution. We investigate the stability of such bundles with respect to hydrophobicity, the strength of the electrostatic interaction and the bundle size. We show that for the parameter range relevant for sulfonated poly(para-phenylenes) (PPP) one finds a stable finite bundle size. In a more generic model we also show the influence of the length of the precursor oligomer on the stability of the bundles. We also point out that our model has close similarities to DNA solutions with added condensing agents, hinting at the possibility that the size of DNA aggregates is, under certain circumstances, thermodynamically limited.

Polyelectrolyte bundles

International Nuclear Information System (INIS)

Limbach, H J; Sayar, M; Holm, C

2004-01-01

Using extensive molecular dynamics simulations we study the behaviour of polyelectrolytes with hydrophobic side chains, which are known to form cylindrical micelles in aqueous solution. We investigate the stability of such bundles with respect to hydrophobicity, the strength of the electrostatic interaction and the bundle size. We show that for the parameter range relevant for sulfonated poly(para-phenylenes) (PPP) one finds a stable finite bundle size. In a more generic model we also show the influence of the length of the precursor oligomer on the stability of the bundles. We also point out that our model has close similarities to DNA solutions with added condensing agents, hinting at the possibility that the size of DNA aggregates is, under certain circumstances, thermodynamically limited

Polyelectrolyte bundles

Science.gov (United States)

Limbach, H. J.; Sayar, M.; Holm, C.

2004-06-01

Using extensive Molecular Dynamics simulations we study the behavior of polyelectrolytes with hydrophobic side chains, which are known to form cylindrical micelles in aqueous solution. We investigate the stability of such bundles with respect to hydrophobicity, the strength of the electrostatic interaction, and the bundle size. We show that for the parameter range relevant for sulfonated poly-para-phenylenes (PPP) one finds a stable finite bundle size. In a more generic model we also show the influence of the length of the precursor oligomer on the stability of the bundles. We also point out that our model has close similarities to DNA solutions with added condensing agents, hinting to the possibility that the size of DNA aggregates is under certain circumstances thermodynamically limited.

Strategic Aspects of Bundling

International Nuclear Information System (INIS)

Podesta, Marion

2008-01-01

The increase of bundle supply has become widespread in several sectors (for instance in telecommunications and energy fields). This paper review relates strategic aspects of bundling. The main purpose of this paper is to analyze profitability of bundling strategies according to the degree of competition and the characteristics of goods. Moreover, bundling can be used as price discrimination tool, screening device or entry barriers. In monopoly case bundling strategy is efficient to sort consumers in different categories in order to capture a maximum of surplus. However, when competition increases, the profitability on bundling strategies depends on correlation of consumers' reservations values. (author)

Nonabelian bundle 2-gerbes

OpenAIRE

Jurco, Branislav

2009-01-01

We define 2-crossed module bundle 2-gerbes related to general Lie 2-crossed modules and discuss their properties. A 2-crossed module bundle 2-gerbe over a manifold is defined in terms of a so called 2-crossed module bundle gerbe, which is a crossed module bundle gerbe equipped with an extra sructure. It is shown that string structures can be described and classified using 2-crossed module bundle 2-gerbes.

Microtubule dynamics: Caps, catastrophes, and coupled hydrolysis

DEFF Research Database (Denmark)

Flyvbjerg, H.; Holy, T.E.; Leibler, S.

1996-01-01

An effective theory is formulated for the dynamics of the guanosine triphosphate (GTP) cap believed to stabilize growing microtubules. The theory provides a ''coarse-grained'' description of the cap's dynamics. ''Microscopic'' details, such as the microtubule lattice structure and the fate of its...

Nonlinear dynamics of C-terminal tails in cellular microtubules

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Sekulic, Dalibor L.; Sataric, Bogdan M.; Zdravkovic, Slobodan; Bugay, Aleksandr N.; Sataric, Miljko V.

2016-07-01

The mechanical and electrical properties, and information processing capabilities of microtubules are the permanent subject of interest for carrying out experiments in vitro and in silico, as well as for theoretical attempts to elucidate the underlying processes. In this paper, we developed a new model of the mechano-electrical waves elicited in the rows of very flexible C-terminal tails which decorate the outer surface of each microtubule. The fact that C-terminal tails play very diverse roles in many cellular functions, such as recruitment of motor proteins and microtubule-associated proteins, motivated us to consider their collective dynamics as the source of localized waves aimed for communication between microtubule and associated proteins. Our approach is based on the ferroelectric liquid crystal model and it leads to the effective asymmetric double-well potential which brings about the conditions for the appearance of kink-waves conducted by intrinsic electric fields embedded in microtubules. These kinks can serve as the signals for control and regulation of intracellular traffic along microtubules performed by processive motions of motor proteins, primarly from kinesin and dynein families. On the other hand, they can be precursors for initiation of dynamical instability of microtubules by recruiting the proper proteins responsible for the depolymerization process.

Branching microtubule nucleation in Xenopus egg extracts mediated by augmin and TPX2

Science.gov (United States)

Petry, Sabine; Groen, Aaron C.; Ishihara, Keisuke; Mitchison, Timothy J.; Vale, Ronald D.

2013-01-01

Summary The microtubules that comprise mitotic spindles in animal cells are nucleated at centrosomes and by spindle assembly factors that are activated in the vicinity of chromatin. Indirect evidence also has suggested that microtubules might be nucleated from pre-existing microtubules throughout the spindle, but this process has not been observed directly. Here, we demonstrate microtubule nucleation from the sides of existing microtubules in meiotic Xenopus egg extracts. Daughter microtubules grow at a low branch angle and with the same polarity as mother filaments. Branching microtubule nucleation requires gamma-tubulin and augmin and is stimulated by GTP-bound Ran and its effector TPX2, factors previously implicated in chromatin-stimulated nucleation. Because of the rapid amplification of microtubule numbers and the preservation of microtubule polarity, microtubule-dependent microtubule nucleation is well suited for spindle assembly and maintenance. PMID:23415226

Polycation induced actin bundles.

Science.gov (United States)

Muhlrad, Andras; Grintsevich, Elena E; Reisler, Emil

2011-04-01

Three polycations, polylysine, the polyamine spermine and the polycationic protein lysozyme were used to study the formation, structure, ionic strength sensitivity and dissociation of polycation-induced actin bundles. Bundles form fast, simultaneously with the polymerization of MgATP-G-actins, upon the addition of polycations to solutions of actins at low ionic strength conditions. This indicates that nuclei and/or nascent filaments bundle due to attractive, electrostatic effect of polycations and the neutralization of repulsive interactions of negative charges on actin. The attractive forces between the filaments are strong, as shown by the low (in nanomolar range) critical concentration of their bundling at low ionic strength. These bundles are sensitive to ionic strength and disassemble partially in 100 mM NaCl, but both the dissociation and ionic strength sensitivity can be countered by higher polycation concentrations. Cys374 residues of actin monomers residing on neighboring filaments in the bundles can be cross-linked by the short span (5.4Å) MTS-1 (1,1-methanedyl bismethanethiosulfonate) cross-linker, which indicates a tight packing of filaments in the bundles. The interfilament cross-links, which connect monomers located on oppositely oriented filaments, prevent disassembly of bundles at high ionic strength. Cofilin and the polysaccharide polyanion heparin disassemble lysozyme induced actin bundles more effectively than the polylysine-induced bundles. The actin-lysozyme bundles are pathologically significant as both proteins are found in the pulmonary airways of cystic fibrosis patients. Their bundles contribute to the formation of viscous mucus, which is the main cause of breathing difficulties and eventual death in this disorder. Copyright © 2011 Elsevier B.V. All rights reserved.

Kinesin expands and stabilizes the GDP-microtubule lattice

Science.gov (United States)

Peet, Daniel R.; Burroughs, Nigel J.; Cross, Robert A.

2018-05-01

Kinesin-1 is a nanoscale molecular motor that walks towards the fast-growing (plus) ends of microtubules, hauling molecular cargo to specific reaction sites in cells. Kinesin-driven transport is central to the self-organization of eukaryotic cells and shows great promise as a tool for nano-engineering1. Recent work hints that kinesin may also play a role in modulating the stability of its microtubule track, both in vitro2,3 and in vivo4, but the results are conflicting5-7 and the mechanisms are unclear. Here, we report a new dimension to the kinesin-microtubule interaction, whereby strong-binding state (adenosine triphosphate (ATP)-bound and apo) kinesin-1 motor domains inhibit the shrinkage of guanosine diphosphate (GDP) microtubules by up to two orders of magnitude and expand their lattice spacing by 1.6%. Our data reveal an unexpected mechanism by which the mechanochemical cycles of kinesin and tubulin interlock, and so allow motile kinesins to influence the structure, stability and mechanics of their microtubule track.

Quantitative Analysis of Tau-Microtubule Interaction Using FRET

Directory of Open Access Journals (Sweden)

Isabelle L. Di Maïo

2014-08-01

Full Text Available The interaction between the microtubule associated protein, tau and the microtubules is investigated. A fluorescence resonance energy transfer (FRET assay was used to determine the distance separating tau to the microtubule wall, as well as the binding parameters of the interaction. By using microtubules stabilized with Flutax-2 as donor and tau labeled with rhodamine as acceptor, a donor-to-acceptor distance of 54 ± 1 Å was found. A molecular model is proposed in which Flutax-2 is directly accessible to tau-rhodamine molecules for energy transfer. By titration, we calculated the stoichiometric dissociation constant to be equal to 1.0 ± 0.5 µM. The influence of the C-terminal tails of αβ-tubulin on the tau-microtubule interaction is presented once a procedure to form homogeneous solution of cleaved tubulin has been determined. The results indicate that the C-terminal tails of α- and β-tubulin by electrostatic effects and of recruitment seem to be involved in the binding mechanism of tau.

Hexavalent chromium-induced differential disruption of cortical microtubules in some Fabaceae species is correlated with acetylation of α-tubulin.

Science.gov (United States)

Eleftheriou, Eleftherios P; Adamakis, Ioannis-Dimosthenis S; Michalopoulou, Vasiliki A

2016-03-01

The effects of hexavalent chromium [Cr(VI)] on the cortical microtubules (MTs) of five species of the Fabaceae family (Vicia faba, Pisum sativum, Vigna sinensis, Vigna angularis, and Medicago sativa) were investigated by confocal laser scanning microscopy after immunolocalization of total tubulin with conventional immunofluorescence techniques and of acetylated α-tubulin with the specific 6-11B-1 monoclonal antibody. Moreover, total α-tubulin and acetylated α-tubulin were quantified by Western immunoblotting and scanning densitometry. Results showed the universality of Cr(VI) detrimental effects to cortical MTs, which proved to be a sensitive and reliable subcellular marker for monitoring Cr(VI) toxicity in plant cells. However, a species-specific response was recorded, and a correlation of MT disturbance with the acetylation status of α-tubulin was demonstrated. In V. faba, MTs were depolymerized at the gain of cytoplasmic tubulin background and displayed low α-tubulin acetylation, while in P. sativum, V. sinensis, V. angularis, and M. sativa, MTs became bundled and changed orientation from perpendicular to oblique or longitudinal. Bundled MTs were highly acetylated as determined by both immunofluorescence and Western immunoblotting. Tubulin acetylation in P. sativum and M. sativa preceded MT bundling; in V. sinensis it followed MT derangement, while in V. angularis the two phenomena coincided. Total α-tubulin remained constant in all treatments. Should acetylation be an indicator of MT stabilization, it is deduced that bundled MTs became stabilized, lost their dynamic properties, and were rendered inactive. Results of this report allow the conclusion that Cr(VI) toxicity disrupts MTs and deranges the MT-mediated functions either by depolymerizing or stabilizing them.

Multiscale modeling and simulation of microtubule-motor-protein assemblies.

Science.gov (United States)

Gao, Tong; Blackwell, Robert; Glaser, Matthew A; Betterton, M D; Shelley, Michael J

2015-01-01

Microtubules and motor proteins self-organize into biologically important assemblies including the mitotic spindle and the centrosomal microtubule array. Outside of cells, microtubule-motor mixtures can form novel active liquid-crystalline materials driven out of equilibrium by adenosine triphosphate-consuming motor proteins. Microscopic motor activity causes polarity-dependent interactions between motor proteins and microtubules, but how these interactions yield larger-scale dynamical behavior such as complex flows and defect dynamics is not well understood. We develop a multiscale theory for microtubule-motor systems in which Brownian dynamics simulations of polar microtubules driven by motors are used to study microscopic organization and stresses created by motor-mediated microtubule interactions. We identify polarity-sorting and crosslink tether relaxation as two polar-specific sources of active destabilizing stress. We then develop a continuum Doi-Onsager model that captures polarity sorting and the hydrodynamic flows generated by these polar-specific active stresses. In simulations of active nematic flows on immersed surfaces, the active stresses drive turbulent flow dynamics and continuous generation and annihilation of disclination defects. The dynamics follow from two instabilities, and accounting for the immersed nature of the experiment yields unambiguous characteristic length and time scales. When turning off the hydrodynamics in the Doi-Onsager model, we capture formation of polar lanes as observed in the Brownian dynamics simulation.

Multiscale modeling and simulation of microtubule-motor-protein assemblies

Science.gov (United States)

Gao, Tong; Blackwell, Robert; Glaser, Matthew A.; Betterton, M. D.; Shelley, Michael J.

2015-12-01

Microtubules and motor proteins self-organize into biologically important assemblies including the mitotic spindle and the centrosomal microtubule array. Outside of cells, microtubule-motor mixtures can form novel active liquid-crystalline materials driven out of equilibrium by adenosine triphosphate-consuming motor proteins. Microscopic motor activity causes polarity-dependent interactions between motor proteins and microtubules, but how these interactions yield larger-scale dynamical behavior such as complex flows and defect dynamics is not well understood. We develop a multiscale theory for microtubule-motor systems in which Brownian dynamics simulations of polar microtubules driven by motors are used to study microscopic organization and stresses created by motor-mediated microtubule interactions. We identify polarity-sorting and crosslink tether relaxation as two polar-specific sources of active destabilizing stress. We then develop a continuum Doi-Onsager model that captures polarity sorting and the hydrodynamic flows generated by these polar-specific active stresses. In simulations of active nematic flows on immersed surfaces, the active stresses drive turbulent flow dynamics and continuous generation and annihilation of disclination defects. The dynamics follow from two instabilities, and accounting for the immersed nature of the experiment yields unambiguous characteristic length and time scales. When turning off the hydrodynamics in the Doi-Onsager model, we capture formation of polar lanes as observed in the Brownian dynamics simulation.

Nefness of adjoint bundles for ample vector bundles

Directory of Open Access Journals (Sweden)

Hidetoshi Maeda

1995-11-01

Full Text Available Let E be an ample vector bundle of rank >1 on a smooth complex projective variety X of dimension n. This paper gives a classification of pairs (X,E whose adjoint bundles K_X+det E are not nef in the case when  r=n-2.

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.

Microtubule protein ADP-ribosylation in vitro leads to assembly inhibition and rapid depolymerization

Energy Technology Data Exchange (ETDEWEB)

Scaife, R.M. (Fred Hutchinson Cancer Research Center, Seattle, WA (United States)); Wilson, L. (Univ. of California, Santa Barbara (United States)); Purich, D.L. (Univ. of Florida, Gainesville (United States))

1992-01-14

Bovine brain microtubule protein, containing both tubulin and microtubule-associated proteins, undergoes ADP-ribosylation in the presence of ({sup 14}C)NAD{sup +} and a turkey erythrocyte mono-ADP-ribosyltransferase in vitro. The modification reaction could be demonstrated in crude brain tissue extracts where selective ADP-ribosylation of both the {alpha} and {beta} chains of tubulin and of the high molecular weight microtubule-associated protein MAP-2 occurred. In experiments with purified microtubule protein, tubulin dimer, the high molecular weight microtubule-associated protein MAP-2, and another high molecular weight microtubule-associated protein which may be a MAP-1 species were heavily labeled. Tubulin and MAP-2 incorporated ({sup 14}C)ADP-ribose to an average extent of approximately 2.4 and 30 mol of ADP-ribose/mol of protein, respectively. Assembly of microtubule protein into microtubules in vitro was inhibited by ADP-ribosylation, and incubation of assembled steady-state microtubules with ADP-ribosyltransferase and NAD{sup +} resulted in rapid depolymerization of the microtubules. Thus, the eukaryotic enzyme can ADP-ribosylate tubulin and microtubule-associated proteins to much greater extents than previously observed with cholera and pertussis toxins, and the modification can significantly modulate microtubule assembly and disassembly.

Structural differences between yeast and mammalian microtubules revealed by cryo-EM

Energy Technology Data Exchange (ETDEWEB)

Howes, Stuart C. [Univ. of California, Berkeley, CA (United States). Biophysics Graduate Group; Geyer, Elisabeth A. [Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Dept. of Biophysics; Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Dept. of Biochemistry; LaFrance, Benjamin [Univ. of California, Berkeley, CA (United States). Molecular and Cell Biology Graduate Program; Zhang, Rui [Univ. of California, Berkeley, CA (United States). Howard Hughes Medical Inst.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging Division; Kellogg, Elizabeth H. [Univ. of California, Berkeley, CA (United States). Howard Hughes Medical Inst.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging Division; Westermann, Stefan [Univ. of Duisburg-Essen, Essen (Germany). Dept. of Molecular Genetics, Center for Medical Biotechnology; Rice, Luke M. [Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Dept. of Biophysics; Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Dept. of Biochemistry; Nogales, Eva [Univ. of California, Berkeley, CA (United States). Howard Hughes Medical Inst.; Univ. of California, Berkeley, CA (United States). Dept. of Molecular Biology and California Inst. for Quantitative Biosciences; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging Division

2017-06-26

Microtubules are polymers of αβ-tubulin heterodimers essential for all eukaryotes. Despite sequence conservation, there are significant structural differences between microtubules assembled in vitro from mammalian or budding yeast tubulin. Yeast MTs were not observed to undergo compaction at the interdimer interface as seen for mammalian microtubules upon GTP hydrolysis. Lack of compaction might reflect slower GTP hydrolysis or a different degree of allosteric coupling in the lattice. The microtubule plus end–tracking protein Bim1 binds yeast microtubules both between αβ-tubulin heterodimers, as seen for other organisms, and within tubulin dimers, but binds mammalian tubulin only at interdimer contacts. At the concentrations used in cryo-electron microscopy, Bim1 causes the compaction of yeast microtubules and induces their rapid disassembly. In conclusion, our studies demonstrate structural differences between yeast and mammalian microtubules that likely underlie their differing polymerization dynamics. These differences may reflect adaptations to the demands of different cell size or range of physiological growth temperatures.

Model for the orientational ordering of the plant microtubule cortical array

Science.gov (United States)

Hawkins, Rhoda J.; Tindemans, Simon H.; Mulder, Bela M.

2010-07-01

The plant microtubule cortical array is a striking feature of all growing plant cells. It consists of a more or less homogeneously distributed array of highly aligned microtubules connected to the inner side of the plasma membrane and oriented transversely to the cell growth axis. Here, we formulate a continuum model to describe the origin of orientational order in such confined arrays of dynamical microtubules. The model is based on recent experimental observations that show that a growing cortical microtubule can interact through angle dependent collisions with pre-existing microtubules that can lead either to co-alignment of the growth, retraction through catastrophe induction or crossing over the encountered microtubule. We identify a single control parameter, which is fully determined by the nucleation rate and intrinsic dynamics of individual microtubules. We solve the model analytically in the stationary isotropic phase, discuss the limits of stability of this isotropic phase, and explicitly solve for the ordered stationary states in a simplified version of the model.

Implementing a pressure ulcer prevention bundle in an adult intensive care.

Science.gov (United States)

Tayyib, Nahla; Coyer, Fiona; Lewis, Peter A

2016-12-01

The incidence of pressure ulcers (PUs) in intensive care units (ICUs) is high and numerous strategies have been implemented to address this issue. One approach is the use of a PU prevention bundle. However, to ensure success care bundle implementation requires monitoring to evaluate the care bundle compliance rate, and to evaluate the effectiveness of implementation strategies in facilitating practice change. The aims of this study were to appraise the implementation of a series of high impact intervention care bundle components directed at preventing the development of PUs, within ICU, and to evaluate the effectiveness of strategies used to enhance the implementation compliance. An observational prospective study design was used. Implementation strategies included regular education, training, audit and feed-back and the presence of a champion in the ICU. Implementation compliance was measured along four time points using a compliance checklist. Of the 60 registered nurses (RNs) working in the critical care setting, 11 participated in this study. Study participants demonstrated a high level of compliance towards the PU prevention bundle implementation (78.1%), with 100% participant acceptance. No significant differences were found between participants' demographic characteristics and the compliance score. There was a significant effect for time in the implementation compliance (Wilks Lambda=0.29, F (3, 8)=6.35, p<0.016), indicating that RNs needed time to become familiar with the bundle and routinely implement it into their practice. PU incidence was not influenced by the compliance level of participants. The implementation strategies used showed a positive impact on compliance. Assessing and evaluating implementation compliance is critical to achieve a desired outcome (reduction in PU incidence). This study's findings also highlighted that while RNs needed time to familiarise themselves with the care bundle elements, their clinical practice was congruent with the

Cyclin G2 is a centrosome-associated nucleocytoplasmic shuttling protein that influences microtubule stability and induces a p53-dependent cell cycle arrest

International Nuclear Information System (INIS)

Arachchige Don, Aruni S.; Dallapiazza, Robert F.; Bennin, David A.; Brake, Tiffany; Cowan, Colleen E.; Horne, Mary C.

2006-01-01

Cyclin G2 is an atypical cyclin that associates with active protein phosphatase 2A. Cyclin G2 gene expression correlates with cell cycle inhibition; it is significantly upregulated in response to DNA damage and diverse growth inhibitory stimuli, but repressed by mitogenic signals. Ectopic expression of cyclin G2 promotes cell cycle arrest, cyclin dependent kinase 2 inhibition and the formation of aberrant nuclei [Bennin, D. A., Don, A. S., Brake, T., McKenzie, J. L., Rosenbaum, H., Ortiz, L., DePaoli-Roach, A. A., and Horne, M. C. (2002). Cyclin G2 associates with protein phosphatase 2A catalytic and regulatory B' subunits in active complexes and induces nuclear aberrations and a G 1 /S-phase cell cycle arrest. J Biol Chem 277, 27449-67]. Here we report that endogenous cyclin G2 copurifies with centrosomes and microtubules (MT) and that ectopic G2 expression alters microtubule stability. We find exogenous and endogenous cyclin G2 present at microtubule organizing centers (MTOCs) where it colocalizes with centrosomal markers in a variety of cell lines. We previously reported that cyclin G2 forms complexes with active protein phosphatase 2A (PP2A) and colocalizes with PP2A in a detergent-resistant compartment. We now show that cyclin G2 and PP2A colocalize at MTOCs in transfected cells and that the endogenous proteins copurify with isolated centrosomes. Displacement of the endogenous centrosomal scaffolding protein AKAP450 that anchors PP2A at the centrosome resulted in the depletion of centrosomal cyclin G2. We find that ectopic expression of cyclin G2 induces microtubule bundling and resistance to depolymerization, inhibition of polymer regrowth from MTOCs and a p53-dependent cell cycle arrest. Furthermore, we determined that a 100 amino acid carboxy-terminal region of cyclin G2 is sufficient to both direct GFP localization to centrosomes and induce cell cycle inhibition. Colocalization of endogenous cyclin G2 with only one of two GFP-centrin-tagged centrioles, the

Aggregation of SND1 in Stress Granules is Associated with the Microtubule Cytoskeleton During Heat Shock Stimulus.

Science.gov (United States)

Shao, Jie; Gao, Fei; Zhang, Bingbing; Zhao, Meng; Zhou, Yunli; He, Jinyan; Ren, Li; Yao, Zhi; Yang, Jie; Su, Chao; Gao, Xingjie

2017-12-01

Stress granules (SGs) are dynamic dense structures in the cytoplasm that form in response to a variety of environmental stress stimuli. Staphylococcal nuclease and Tudor domain containing 1 (SND1) is a type of RNA-binding protein and has been identified as a transcriptional co-activator. Our previous studies have shown that SND1 is a component of the stress granule, which forms under stress conditions. Here, we observed that SND1 granules were often surrounded by ɑ-tubulin-microtubules in 45°C-treated HeLa cells at 15 min or colocalized with microtubules at 30 or 45 min. Furthermore, Nocodazole-mediated microtubule depolymerization could significantly affect the efficient recruitment of SND1 proteins to the SGs during heat shock stress. In addition, the 45°C heat shock mediated the enhancement of eIF2α phosphorylation, which was not affected by treatment with Nocodazole, an agent that disrupts the cytoskeleton. The intact microtubule cytoskeletal tracks are important for the efficient assembly of SND1 granules under heat shock stress and may facilitate SND1 shuttling between cytoplasmic RNA foci. Anat Rec, 300:2192-2199, 2017. © 2017 The Authors The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists. Copyright © 2017 The Authors The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.

Evaluation of bundle duct interaction by out of pile compressive test of FBR bundles. FFTF type bundle

Energy Technology Data Exchange (ETDEWEB)

Tanaka, Kosuke; Yamamoto, Yuji; Nagamine, Tsuyoshi; Maeda, Koji [Japan Nuclear Cycle Development Inst., Oarai, Ibaraki (Japan). Oarai Engineering Center

2000-10-01

Bundle duct interaction (BDI) caused by expansion of fuel pin bundle becomes one of the main limiting factors for fuel life times. Then, it is important for the design of fast reactor fuel assembly to understand the BDI behavior in detail. In order to understand the BDI behavior, out of pile compressive tests were conducted for FFTF type bundle by use of X-ray CT equipment. In these compressive tests, two type bundles with different accuracy of initial wire position were conducted. The objective of this test is to evaluate the influence of the initial error from standard position of wire at the same axial position. The locations of the pins and the duct flats are analyzed from CT image data. Quantitative evaluation was performed at the CT image data and discussed the bundle deformation status under BDI condition. Following results are obtained. 1) The accuracy of initial wire position is strongly depends on the pin-to-duct contact behavior. In the case of bundle with large error from standard position, pin-to-duct contact is delayed. 2) The BDI mitigation of the bundle with small error from standard wire position is following: The elastic ovality is the dominant deformation in mild BDI condition, then the wire dispersion and pin dispersion are occurred in severe BDI condition. 3) The BDI mitigation of the bundle with large error from standard wire position is following: The elastic ovality and local bowing of pins with large error from standard wire position are occurred in mild BDI condition, then pin dispersion is occurred around pins with large error from standard wire position, finally wire dispersion is occurred in severe BDI condition. 4) The existence of pins with large error from standard wire position is effective to delay the pin-to-duct contact, but the existence of these pins is possible to contact of pin- to- pin. (author)

The XMAP215 Ortholog Alp14 Promotes Microtubule Nucleation in Fission Yeast.

Science.gov (United States)

Flor-Parra, Ignacio; Iglesias-Romero, Ana Belén; Chang, Fred

2018-06-04

The organization and number of microtubules (MTs) in a cell depend on the proper regulation of MT nucleation. Currently, the mechanism of nucleation is the most poorly understood aspect of MT dynamics. XMAP215/chTOG/Alp14/Stu2 proteins are MT polymerases that stimulate MT polymerization at MT plus ends by binding and releasing tubulin dimers. Although these proteins also localize to MT organizing centers and have nucleating activity in vitro, it is not yet clear whether these proteins participate in MT nucleation in vivo. Here, we demonstrate that in the fission yeast Schizosaccharomyces pombe, the XMAP215 ortholog Alp14 is critical for efficient MT nucleation in vivo. In multiple assays, loss of Alp14 function led to reduced nucleation rate and numbers of interphase MT bundles. Conversely, activation of Alp14 led to increased nucleation frequency. Alp14 associated with Mto1 and γ-tubulin complex components, and artificially targeting Alp14 to the γ-tubulin ring complexes (γ-TuRCs) stimulated nucleation. In imaging individual nucleation events, we found that Alp14 transiently associated with a γ-tubulin particle shortly before the appearance of a new MT. The transforming acidic coiled-coil (TACC) ortholog Alp7 mediated the localization of Alp14 at nucleation sites but not plus ends, and was required for efficient nucleation but not for MT polymerization. Our findings provide the strongest evidence to date that Alp14 serves as a critical MT nucleation factor in vivo. We suggest a model in which Alp14 associates with the γ-tubulin complex in an Alp7-dependent manner to facilitate the assembly or stabilization of the nascent MT. Copyright © 2018 Elsevier Ltd. All rights reserved.

Four-stranded mini microtubules formed by Prosthecobacter BtubAB show dynamic instability.

Science.gov (United States)

Deng, Xian; Fink, Gero; Bharat, Tanmay A M; He, Shaoda; Kureisaite-Ciziene, Danguole; Löwe, Jan

2017-07-18

Microtubules, the dynamic, yet stiff hollow tubes built from αβ-tubulin protein heterodimers, are thought to be present only in eukaryotic cells. Here, we report a 3.6-Å helical reconstruction electron cryomicroscopy structure of four-stranded mini microtubules formed by bacterial tubulin-like Prosthecobacter dejongeii BtubAB proteins. Despite their much smaller diameter, mini microtubules share many key structural features with eukaryotic microtubules, such as an M-loop, alternating subunits, and a seam that breaks overall helical symmetry. Using in vitro total internal reflection fluorescence microscopy, we show that bacterial mini microtubules treadmill and display dynamic instability, another hallmark of eukaryotic microtubules. The third protein in the btub gene cluster, BtubC, previously known as "bacterial kinesin light chain," binds along protofilaments every 8 nm, inhibits BtubAB mini microtubule catastrophe, and increases rescue. Our work reveals that some bacteria contain regulated and dynamic cytomotive microtubule systems that were once thought to be only useful in much larger and sophisticated eukaryotic cells.

Nonlinear dynamics of C–terminal tails in cellular microtubules

Energy Technology Data Exchange (ETDEWEB)

Sekulic, Dalibor L., E-mail: dalsek@uns.ac.rs; Sataric, Bogdan M.; Sataric, Miljko V. [University of Novi Sad, Faculty of Technical Sciences, Novi Sad (Serbia); Zdravkovic, Slobodan [University of Belgrade, Institute of Nuclear Sciences Vinca, Belgrade (Serbia); Bugay, Aleksandr N. [Laboratory of Radiation Biology, Joint Institute for Nuclear Research, Dubna (Russian Federation)

2016-07-15

The mechanical and electrical properties, and information processing capabilities of microtubules are the permanent subject of interest for carrying out experiments in vitro and in silico, as well as for theoretical attempts to elucidate the underlying processes. In this paper, we developed a new model of the mechano–electrical waves elicited in the rows of very flexible C–terminal tails which decorate the outer surface of each microtubule. The fact that C–terminal tails play very diverse roles in many cellular functions, such as recruitment of motor proteins and microtubule–associated proteins, motivated us to consider their collective dynamics as the source of localized waves aimed for communication between microtubule and associated proteins. Our approach is based on the ferroelectric liquid crystal model and it leads to the effective asymmetric double-well potential which brings about the conditions for the appearance of kink–waves conducted by intrinsic electric fields embedded in microtubules. These kinks can serve as the signals for control and regulation of intracellular traffic along microtubules performed by processive motions of motor proteins, primarly from kinesin and dynein families. On the other hand, they can be precursors for initiation of dynamical instability of microtubules by recruiting the proper proteins responsible for the depolymerization process.

Nonlinear dynamics of C–terminal tails in cellular microtubules

International Nuclear Information System (INIS)

Sekulic, Dalibor L.; Sataric, Bogdan M.; Sataric, Miljko V.; Zdravkovic, Slobodan; Bugay, Aleksandr N.

2016-01-01

The mechanical and electrical properties, and information processing capabilities of microtubules are the permanent subject of interest for carrying out experiments in vitro and in silico, as well as for theoretical attempts to elucidate the underlying processes. In this paper, we developed a new model of the mechano–electrical waves elicited in the rows of very flexible C–terminal tails which decorate the outer surface of each microtubule. The fact that C–terminal tails play very diverse roles in many cellular functions, such as recruitment of motor proteins and microtubule–associated proteins, motivated us to consider their collective dynamics as the source of localized waves aimed for communication between microtubule and associated proteins. Our approach is based on the ferroelectric liquid crystal model and it leads to the effective asymmetric double-well potential which brings about the conditions for the appearance of kink–waves conducted by intrinsic electric fields embedded in microtubules. These kinks can serve as the signals for control and regulation of intracellular traffic along microtubules performed by processive motions of motor proteins, primarly from kinesin and dynein families. On the other hand, they can be precursors for initiation of dynamical instability of microtubules by recruiting the proper proteins responsible for the depolymerization process.

Assessment of CHF characteristics at subcooled conditions for the CANDU CANFLEX bundle

International Nuclear Information System (INIS)

Onder, E.N.; Leung, L.K.H.

2011-01-01

An analysis has been performed to assess the Critical Heat Flux (CHF) characteristics for the CANFLEX bundle at subcooled conditions. CHF characteristics for CANDU bundles have been established from experiments using full-scale bundle simulators. These experiments covered flow conditions of interest to normal operation and postulated loss-of-flow and small break loss-of-coolant accidents. Experimental CHF values obtained from these experiments were applied to develop correlations for analyses of regional overpower protection and safety trips. These correlations are applicable to the saturated region in the reference uncrept channel and the slightly subcooled region in postulated high-creep channels. Expanding the CHF data to subcooled conditions facilitates the evaluation of the margin to dryout at upstream bundle locations, even though dryout occurrences are not anticipated there. In view of the lack of experimental data, the ASSERT-PV subchannel code has been applied to establish CHF values at low qualities and high subcoolings (thermodynamic qualities corresponding to -25%). These CHF values have been applied to extend the CHF correlation to the highly subcooled conditions. (author)

Friction factors referring to laminar flow through pipe bundles with longitudinal webs

Energy Technology Data Exchange (ETDEWEB)

Schenkel, G

1983-09-01

Pipe bundles with continuous webs or ribs between adjacent pipes, as well as between outer pipes and channel walls, are much more vibrational proof than web-free systems. In addition, the change-over from a multiple-connected web-free cross-section to a set of singly-connected cross-sections facilitates the calculation of friction factors. The investigation is concerned with isothermal steady fully-developed laminar flow of Newtonian fluids. In particularly, pipe bundles with squares and hexagonal arrays in respective channels are treated. Friction factors for the subchannels are taken from a former paper of the author.

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).

TgICMAP1 is a novel microtubule binding protein in Toxoplasma gondii.

Directory of Open Access Journals (Sweden)

Aoife T Heaslip

Full Text Available The microtubule cytoskeleton provides essential structural support for all eukaryotic cells and can be assembled into various higher order structures that perform drastically different functions. Understanding how microtubule-containing assemblies are built in a spatially and temporally controlled manner is therefore fundamental to understanding cell physiology. Toxoplasma gondii, a protozoan parasite, contains at least five distinct tubulin-containing structures, the spindle pole, centrioles, cortical microtubules, the conoid, and the intra-conoid microtubules. How these five structurally and functionally distinct sets of tubulin containing structures are constructed and maintained in the same cell is an intriguing problem. Previously, we performed a proteomic analysis of the T. gondii apical complex, a cytoskeletal complex located at the apical end of the parasite that is composed of the conoid, three ring-like structures, and the two short intra-conoid microtubules. Here we report the characterization of one of the proteins identified in that analysis, TgICMAP1. We show that TgICMAP1 is a novel microtubule binding protein that can directly bind to microtubules in vitro and stabilizes microtubules when ectopically expressed in mammalian cells. Interestingly, in T. gondii, TgICMAP1 preferentially binds to the intra-conoid microtubules, providing us the first molecular tool to investigate the intra-conoid microtubule assembly process during daughter construction.

Oscillatory fluid flow influences primary cilia and microtubule mechanics.

Science.gov (United States)

Espinha, Lina C; Hoey, David A; Fernandes, Paulo R; Rodrigues, Hélder C; Jacobs, Christopher R

2014-07-01

Many tissues are sensitive to mechanical stimuli; however, the mechanotransduction mechanism used by cells remains unknown in many cases. The primary cilium is a solitary, immotile microtubule-based extension present on nearly every mammalian cell which extends from the basal body. The cilium is a mechanosensitive organelle and has been shown to transduce fluid flow-induced shear stress in tissues, such as the kidney and bone. The majority of microtubules assemble from the mother centriole (basal body), contributing significantly to the anchoring of the primary cilium. Several studies have attempted to quantify the number of microtubules emanating from the basal body and the results vary depending on the cell type. It has also been shown that cellular response to shear stress depends on microtubular integrity. This study hypothesizes that changing the microtubule attachment of primary cilia in response to a mechanical stimulus could change primary cilia mechanics and, possibly, mechanosensitivity. Oscillatory fluid flow was applied to two different cell types and the microtubule attachment to the ciliary base was quantified. For the first time, an increase in microtubules around primary cilia both with time and shear rate in response to oscillatory fluid flow stimulation was demonstrated. Moreover, it is presented that the primary cilium is required for this loading-induced cellular response. This study has demonstrated a new role for the cilium in regulating alterations in the cytoplasmic microtubule network in response to mechanical stimulation, and therefore provides a new insight into how cilia may regulate its mechanics and thus the cells mechanosensitivity. Copyright © 2014 Wiley Periodicals, Inc.

Quantitative analysis of microtubule orientation in interdigitated leaf pavement cells.

Science.gov (United States)

Akita, Kae; Higaki, Takumi; Kutsuna, Natsumaro; Hasezawa, Seiichiro

2015-01-01

Leaf pavement cells are shaped like a jigsaw puzzle in most dicotyledon species. Molecular genetic studies have identified several genes required for pavement cells morphogenesis and proposed that microtubules play crucial roles in the interdigitation of pavement cells. In this study, we performed quantitative analysis of cortical microtubule orientation in leaf pavement cells in Arabidopsis thaliana. We captured confocal images of cortical microtubules in cotyledon leaf epidermis expressing GFP-tubulinβ and quantitatively evaluated the microtubule orientations relative to the pavement cell growth axis using original image processing techniques. Our results showed that microtubules kept parallel orientations to the growth axis during pavement cell growth. In addition, we showed that immersion treatment of seed cotyledons in solutions containing tubulin polymerization and depolymerization inhibitors decreased pavement cell complexity. Treatment with oryzalin and colchicine inhibited the symmetric division of guard mother cells.

Lysosomes are associated with microtubules and not with intermediate filaments in cultured fibroblasts.

OpenAIRE

Collot, M; Louvard, D; Singer, S J

1984-01-01

Double immunofluorescent labeling experiments for lysosomes and either microtubules or vimentin intermediate filaments in cultured well-spread fibroblasts show a remarkable degree of superposition of the lysosomes and the microtubules. Under two different sets of conditions where the microtubules and intermediate filaments are well segregated from one another, the lysosomes remain codistributed with the microtubules. It is suggested that this specific association of lysosomes with microtubule...

Microtubule reorganization in tobacco BY-2 cells stably expressing GFP-MBD

Science.gov (United States)

Granger, C. L.; Cyr, R. J.

2000-01-01

Microtubule organization plays an important role in plant morphogenesis; however, little is known about how microtubule arrays transit from one organized state to another. The use of a genetically incorporated fluorescent marker would allow long-term observation of microtubule behavior in living cells. Here, we have characterized a Nicotiana tabacum L. cv. Bright Yellow 2 (BY-2) cell line that had been stably transformed with a gfp-mbd construct previously demonstrated to label microtubules (J. Marc et al., 1998, Plant Cell 10: 1927-1939). Fluorescence levels were low, but interphase and mitotic microtubule arrays, as well as the transitions between these arrays, could be observed in individual gfp-mbd-transformed cells. By comparing several attributes of transformed and untransformed cells it was concluded that the transgenic cells are not adversely affected by low-level expression of the transgene and that these cells will serve as a useful and accurate model system for observing microtubule reorganization in vivo. Indeed, some initial observations were made that are consistent with the involvement of motor proteins in the transition between the spindle and phragmoplast arrays. Our observations also support the role of the perinuclear region in nucleating microtubules at the end of cell division with a progressive shift of these microtubules and/or nucleating activity to the cortex to form the interphase cortical array.

Mammalian Auditory Hair Cell Bundle Stiffness Affects Frequency Tuning by Increasing Coupling along the Length of the Cochlea.

Science.gov (United States)

Dewey, James B; Xia, Anping; Müller, Ulrich; Belyantseva, Inna A; Applegate, Brian E; Oghalai, John S

2018-06-05

The stereociliary bundles of cochlear hair cells convert mechanical vibrations into the electrical signals required for auditory sensation. While the stiffness of the bundles strongly influences mechanotransduction, its influence on the vibratory response of the cochlear partition is unclear. To assess this, we measured cochlear vibrations in mutant mice with reduced bundle stiffness or with a tectorial membrane (TM) that is detached from the sensory epithelium. We found that reducing bundle stiffness decreased the high-frequency extent and sharpened the tuning of vibratory responses obtained postmortem. Detaching the TM further reduced the high-frequency extent of the vibrations but also lowered the partition's resonant frequency. Together, these results demonstrate that the bundle's stiffness and attachment to the TM contribute to passive longitudinal coupling in the cochlea. We conclude that the stereociliary bundles and TM interact to facilitate passive-wave propagation to more apical locations, possibly enhancing active-wave amplification in vivo. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Bundle Branch Block

Science.gov (United States)

... known cause. Causes can include: Left bundle branch block Heart attacks (myocardial infarction) Thickened, stiffened or weakened ... myocarditis) High blood pressure (hypertension) Right bundle branch block A heart abnormality that's present at birth (congenital) — ...

Microtubule's conformational cap

DEFF Research Database (Denmark)

Flyvbjerg, H.

1999-01-01

The molecular mechanisms that allow elongation of the unstable microtubule lattice remain unclear. It is usually thought that the GDP-liganded tubulin lattice is capped by a small layer of GTP- or GDP-P(i)-liganded molecules, the so called "GTP-cap". Here, we point-out that the elastic properties...

Microtubules: A network for solitary waves

Directory of Open Access Journals (Sweden)

Zdravković Slobodan

2017-01-01

Full Text Available In the present paper we deal with nonlinear dynamics of microtubules. The structure and role of microtubules in cells are explained as well as one of models explaining their dynamics. Solutions of the crucial nonlinear differential equation depend on used mathematical methods. Two commonly used procedures, continuum and semi-discrete approximations, are explained. These solutions are solitary waves usually called as kink solitons, breathers and bell-type solitons. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. III45010

Chromosome Bridges Maintain Kinetochore-Microtubule Attachment throughout Mitosis and Rarely Break during Anaphase.

Science.gov (United States)

Pampalona, Judit; Roscioli, Emanuele; Silkworth, William T; Bowden, Brent; Genescà, Anna; Tusell, Laura; Cimini, Daniela

2016-01-01

Accurate chromosome segregation during cell division is essential to maintain genome stability, and chromosome segregation errors are causally linked to genetic disorders and cancer. An anaphase chromosome bridge is a particular chromosome segregation error observed in cells that enter mitosis with fused chromosomes/sister chromatids. The widely accepted Breakage/Fusion/Bridge cycle model proposes that anaphase chromosome bridges break during mitosis to generate chromosome ends that will fuse during the following cell cycle, thus forming new bridges that will break, and so on. However, various studies have also shown a link between chromosome bridges and aneuploidy and/or polyploidy. In this study, we investigated the behavior and properties of chromosome bridges during mitosis, with the idea to gain insight into the potential mechanism underlying chromosome bridge-induced aneuploidy. We find that only a small number of chromosome bridges break during anaphase, whereas the rest persist through mitosis into the subsequent cell cycle. We also find that the microtubule bundles (k-fibers) bound to bridge kinetochores are not prone to breakage/detachment, thus supporting the conclusion that k-fiber detachment is not the cause of chromosome bridge-induced aneuploidy. Instead, our data suggest that while the microtubules bound to the kinetochores of normally segregating chromosomes shorten substantially during anaphase, the k-fibers bound to bridge kinetochores shorten only slightly, and may even lengthen, during anaphase. This causes some of the bridge kinetochores/chromosomes to lag behind in a position that is proximal to the cell/spindle equator and may cause the bridged chromosomes to be segregated into the same daughter nucleus or to form a micronucleus.

The nucleation of microtubules in Aspergillus nidulans germlings

Directory of Open Access Journals (Sweden)

Cristina de Andrade-Monteiro

1999-09-01

Full Text Available Microtubules are filaments composed of dimers of alpha- and beta-tubulins, which have a variety of functions in living cells. In fungi, the spindle pole bodies usually have been considered to be microtubule-organizing centers. We used the antimicrotubule drug Benomyl in block/release experiments to depolymerize and repolymerize microtubules in Aspergillus nidulans germlings to learn more about the microtubule nucleation process in this filamentous fungus. Twenty seconds after release from Benomyl short microtubules were formed from several bright (immunofluorescent dots distributed along the germlings, suggesting that microtubule nucleation is randomly distributed in A. nidulans germlings. Since nuclear movement is dependent on microtubules in A. nidulans we analyzed whether mutants defective in nuclear distribution along the growing hyphae (nud mutants have some obvious microtubule defect. Cytoplasmic, astral and spindle microtubules were present and appeared to be normal in all nud mutants. However, significant changes in the percentage of short versus long mitotic spindles were observed in nud mutants. This suggests that some of the nuclei of nud mutants do not reach the late stage of cell division at normal temperatures.Microtúbulos são filamentos compostos por dímeros das tubulinas a e b e têm uma variedade de funções nas células vivas. Em fungos, os corpúsculos polares dos fusos são geralmente considerados os centros organizadores dos microtúbulos. Com o objetivo de contribuir para uma melhor compreensão dos processos de nucleação dos microtúbulos no fungo filamentoso A. nidulans, nós utilizamos a droga antimicrotúbulo Benomil em experimentos de bloqueio e liberação para depolimerizar e repolimerizar os microtúbulos. Após 20 segundos de reincubação em meio sem Benomil, pequenos microtúbulos foram formados a partir de pontos distribuídos pela célula, sugerindo que os pontos de nucleação de microtúbulos s

Safety assessment for the CANFLEX-NU fuel bundles with respect to the 37-element fuel bundles

Energy Technology Data Exchange (ETDEWEB)

Suk, H. C.; Lim, H. S. [Korea Atomic Energy Research Institute, Taejon (Korea)

1999-11-01

The KAERI and AECL have jointly developed an advanced CANDU fuel, called CANFLEX-NU fuel bundle. CANFLEX 43-element bundle has some improved features of increased operating margin and enhanced safety compared to the existing 37-element bundle. Since CANFLEX fuel bundle is designed to be compatible with the CANDU-6 reactor design, the behaviour in the thermalhydraulic system will be nearly identical with 37-element bundle. But due to different element design and linear element power distribution between the two bundles, it is expected that CANFLEX fuel behaviour would be different from the behaviour of the 37-element fuel. Therefore, safety assessments on the design basis accidents which result if fuel failures are performed. For all accidents selected, it is observed that the loading of CANFLEX bundle in an existing CANDU-6 reactor would not worsen the reactor safety. It is also predicted that fission product release for CANFLEX fuel bundle generally is lower than that for 37-element bundle. 3 refs., 2 figs., 2 tabs. (Author)

Ibuprofen regulation of microtubule dynamics in cystic fibrosis epithelial cells.

Science.gov (United States)

Rymut, Sharon M; Kampman, Claire M; Corey, Deborah A; Endres, Tori; Cotton, Calvin U; Kelley, Thomas J

2016-08-01

High-dose ibuprofen, an effective anti-inflammatory therapy for the treatment of cystic fibrosis (CF), has been shown to preserve lung function in a pediatric population. Despite its efficacy, few patients receive ibuprofen treatment due to potential renal and gastrointestinal toxicity. The mechanism of ibuprofen efficacy is also unclear. We have previously demonstrated that CF microtubules are slower to reform after depolymerization compared with respective wild-type controls. Slower microtubule dynamics in CF cells are responsible for impaired intracellular transport and are related to inflammatory signaling. Here, it is identified that high-dose ibuprofen treatment in both CF cell models and primary CF nasal epithelial cells restores microtubule reformation rates to wild-type levels, as well as induce extension of microtubules to the cell periphery. Ibuprofen treatment also restores microtubule-dependent intracellular transport monitored by measuring intracellular cholesterol transport. These effects are specific to ibuprofen as other cyclooxygenase inhibitors have no effect on these measures. Effects of ibuprofen are mimicked by stimulation of AMPK and blocked by the AMPK inhibitor compound C. We conclude that high-dose ibuprofen treatment enhances microtubule formation in CF cells likely through an AMPK-related pathway. These findings define a potential mechanism to explain the efficacy of ibuprofen therapy in CF. Copyright © 2016 the American Physiological Society.

Bundling in Place: Translating the NGSS into Place-Based Earth-System Science Curricula

Science.gov (United States)

Semken, S. C.

2016-12-01

Bundling is the process of grouping Performance Expectations (PEs) from the Next Generation Science Standards (NGSS) into coherent units based on a defined topic, idea, question, or phenomenon. Bundling sorts the PEs for a given grade or grade band into a teachable narrative: a key stage in building curriculum, instruction, and assessment from the NGSS. To encourage and facilitate this, bundling guidelines have recently been released on the NGSS website (nextgenscience.org/glossary/bundlesbundling), and example bundles for different grade bands and disciplines are also being developed and posted there. According to these guidelines the iterative process of bundling begins with organization of PEs according to natural connections among them, and alignment of the three NGSS dimensions (Disciplinary Core Ideas, Cross-Cutting Concepts, and Science and Engineering Practices) that underpin each PE. Bundles are grouped by coherence and increasing complexity into courses, and courses into course sets that should encompass all PEs for a grade band. Bundling offers a natural way to translate the NGSS into highly contextualized curricula such as place-based (PB) teaching, which is situated in specific places or regions and focused on natural and cultural features, processes, phenomena, history, and challenges to sustainability therein. Attributes of place and our individual and collective connections to place (sense of place) directly inform PB curriculum, pedagogy, and assessment. PEs can be bundled by their relevance to these themes. Following the NGSS guidelines, I model the process for PB instruction by bundling PEs around the themes of Paleozoic geology and carbonate deposition and their relationships to mining and calcining of limestone in Anthropocene cement production for developing communities. The bundles integrate aspects of Earth history, the carbon cycle, mineral resources, climate change, and sustainability using specific local examples and narratives. They are

Chlorpyrifos, chlorpyrifos-oxon, and diisopropylfluorophosphate inhibit kinesin-dependent microtubule motility

International Nuclear Information System (INIS)

Gearhart, Debra A.; Sickles, Dale W.; Buccafusco, Jerry J.; Prendergast, Mark A.; Terry, Alvin V.

2007-01-01

Diisopropylfluorophosphate, originally developed as a chemical warfare agent, is structurally similar to nerve agents, and chlorpyrifos has extensive worldwide use as an agricultural pesticide. While inhibition of cholinesterases underlies the acute toxicity of these organophosphates, we previously reported impaired axonal transport in the sciatic nerves from rats treated chronically with subthreshold doses of chlorpyrifos. Those data indicate that chlorpyrifos (and/or its active metabolite, chlorpyrifos-oxon) might directly affect the function of kinesin and/or microtubules-the principal proteins that mediate anterograde axonal transport. The current report describes in vitro assays to assess the concentration-dependent effects of chlorpyrifos (0-10 μM), chlorpyrifos-oxon (0-10 μM), and diisopropylfluorophosphate (0-0.59 nM) on kinesin-dependent microtubule motility. Preincubating bovine brain microtubules with the organophosphates did not alter kinesin-mediated microtubule motility. In contrast, preincubation of bovine brain kinesin with diisopropylfluorophosphate, chlorpyrifos, or chlorpyrifos-oxon produced a concentration-dependent increase in the number of locomoting microtubules that detached from the kinesin-coated glass cover slip. Our data suggest that the organophosphates-chlorpyrifos-oxon, chlorpyrifos, and diisopropylfluorophosphate-directly affect kinesin, thereby disrupting kinesin-dependent transport on microtubules. Kinesin-dependent movement of vesicles, organelles, and other cellular components along microtubules is fundamental to the organization of all eukaryotic cells, especially in neurons where organelles and proteins synthesized in the cell body must move down long axons to pre-synaptic sites in nerve terminals. We postulate that disruption of kinesin-dependent intracellular transport could account for some of the long-term effects of organophosphates on the peripheral and central nervous system

Constructing co-Higgs bundles on CP^2

OpenAIRE

Rayan, Steven

2013-01-01

On a complex manifold, a co-Higgs bundle is a holomorphic vector bundle with an endomorphism twisted by the tangent bundle. The notion of generalized holomorphic bundle in Hitchin's generalized geometry coincides with that of co-Higgs bundle when the generalized complex manifold is ordinary complex. Schwarzenberger's rank-2 vector bundle on the projective plane, constructed from a line bundle on the double cover CP^1 \\times CP^1 \\to CP^2, is naturally a co-Higgs bundle, with the twisted endom...

Microtubule–microtubule sliding by kinesin-1 is essential for normal cytoplasmic streaming in Drosophila oocytes

Science.gov (United States)

Lu, Wen; Winding, Michael; Lakonishok, Margot; Wildonger, Jill

2016-01-01

Cytoplasmic streaming in Drosophila oocytes is a microtubule-based bulk cytoplasmic movement. Streaming efficiently circulates and localizes mRNAs and proteins deposited by the nurse cells across the oocyte. This movement is driven by kinesin-1, a major microtubule motor. Recently, we have shown that kinesin-1 heavy chain (KHC) can transport one microtubule on another microtubule, thus driving microtubule–microtubule sliding in multiple cell types. To study the role of microtubule sliding in oocyte cytoplasmic streaming, we used a Khc mutant that is deficient in microtubule sliding but able to transport a majority of cargoes. We demonstrated that streaming is reduced by genomic replacement of wild-type Khc with this sliding-deficient mutant. Streaming can be fully rescued by wild-type KHC and partially rescued by a chimeric motor that cannot move organelles but is active in microtubule sliding. Consistent with these data, we identified two populations of microtubules in fast-streaming oocytes: a network of stable microtubules anchored to the actin cortex and free cytoplasmic microtubules that moved in the ooplasm. We further demonstrated that the reduced streaming in sliding-deficient oocytes resulted in posterior determination defects. Together, we propose that kinesin-1 slides free cytoplasmic microtubules against cortically immobilized microtubules, generating forces that contribute to cytoplasmic streaming and are essential for the refinement of posterior determinants. PMID:27512034

CANFLEX fuel bundle impact test

International Nuclear Information System (INIS)

Chang, Seok Kyu; Chung, C. H.; Park, J. S.; Hong, S. D.; Kim, B. D.

1997-08-01

This document outlines the test results for the impact test of the CANFLEX fuel bundle. Impact test is performed to determine and verify the amount of general bundle shape distortion and defect of the pressure tube that may occur during refuelling. The test specification requires that the fuel bundles and the pressure tube retain their integrities after the impact test under the conservative conditions (10 stationary bundles with 31kg/s flow rate) considering the pressure tube creep. The refuelling simulator operating with pneumatic force and simulated shield plug were fabricated and the velocity/displacement transducer and the high speed camera were also used in this test. The characteristics of the moving bundle (velocity, displacement, impacting force) were measured and analyzed with the impact sensor and the high speed camera system. The important test procedures and measurement results were discussed as follows. 1) Test bundle measurements and the pressure tube inspections 2) Simulated shield plug, outlet flange installation and bundle loading 3) refuelling simulator, inlet flange installation and sensors, high speed camera installation 4) Perform the impact test with operating the refuelling simulator and measure the dynamic characteristics 5) Inspections of the fuel bundles and the pressure tube. (author). 8 refs., 23 tabs., 13 figs

Polycation induced actin bundles

OpenAIRE

Muhlrad, Andras; Grintsevich, Elena E.; Reisler, Emil

2011-01-01

Three polycations, polylysine, the polyamine spermine and the polycationic protein lysozyme were used to study the formation, structure, ionic strength sensitivity and dissociation of polycation-induced actin bundles. Bundles form fast, simultaneously with the polymerization of MgATP-G-actins, upon addition of polycations to solutions of actins at low ionic strength conditions. This indicates that nuclei and/or nascent filaments bundle due to attractive, electrostatic effect of polycations an...

Cellular effects of curcumin on Plasmodium falciparum include disruption of microtubules.

Directory of Open Access Journals (Sweden)

Rimi Chakrabarti

Full Text Available Curcumin has been widely investigated for its myriad cellular effects resulting in reduced proliferation of various eukaryotic cells including cancer cells and the human malaria parasite Plasmodium falciparum. Studies with human cancer cell lines HT-29, Caco-2, and MCF-7 suggest that curcumin can bind to tubulin and induce alterations in microtubule structure. Based on this finding, we investigated whether curcumin has any effect on P. falciparum microtubules, considering that mammalian and parasite tubulin are 83% identical. IC50 of curcumin was found to be 5 µM as compared to 20 µM reported before. Immunofluorescence images of parasites treated with 5 or 20 µM curcumin showed a concentration-dependent effect on parasite microtubules resulting in diffuse staining contrasting with the discrete hemispindles and subpellicular microtubules observed in untreated parasites. The effect on P. falciparum microtubules was evident only in the second cycle for both concentrations tested. This diffuse pattern of tubulin fluorescence in curcumin treated parasites was similar to the effect of a microtubule destabilizing drug vinblastine on P. falciparum. Molecular docking predicted the binding site of curcumin at the interface of alpha and beta tubulin, similar to another destabilizing drug colchicine. Data from predicted drug binding is supported by results from drug combination assays showing antagonistic interactions between curcumin and colchicine, sharing a similar binding site, and additive/synergistic interactions of curcumin with paclitaxel and vinblastine, having different binding sites. This evidence suggests that cellular effects of curcumin are at least, in part, due to its perturbing effect on P. falciparum microtubules. The action of curcumin, both direct and indirect, on P. falciparum microtubules is discussed.

Autocatalytic microtubule nucleation determines the size and mass of Xenopus laevis egg extract spindles.

Science.gov (United States)

Decker, Franziska; Oriola, David; Dalton, Benjamin; Brugués, Jan

2018-01-11

Regulation of size and growth is a fundamental problem in biology. A prominent example is the formation of the mitotic spindle, where protein concentration gradients around chromosomes are thought to regulate spindle growth by controlling microtubule nucleation. Previous evidence suggests that microtubules nucleate throughout the spindle structure. However, the mechanisms underlying microtubule nucleation and its spatial regulation are still unclear. Here, we developed an assay based on laser ablation to directly probe microtubule nucleation events in Xenopus laevis egg extracts. Combining this method with theory and quantitative microscopy, we show that the size of a spindle is controlled by autocatalytic growth of microtubules, driven by microtubule-stimulated microtubule nucleation. The autocatalytic activity of this nucleation system is spatially regulated by the limiting amounts of active microtubule nucleators, which decrease with distance from the chromosomes. This mechanism provides an upper limit to spindle size even when resources are not limiting. © 2018, Decker et al.

Direct evidence for GTP and GDP-Pi intermediates in microtubule assembly

International Nuclear Information System (INIS)

Melki, R.; Carlier, M.F.; Pantaloni, D.

1990-01-01

Identification of the kinetic intermediates in GTP hydrolysis on microtubules and characterization of their assembly properties is essential in understanding microtubule dynamics. By using an improved glass filter assay that selectively traps microtubules with a dead time of 2 s and monitoring taxol-induced rapid assembly of microtubules from [γ- 32 P, 3 H]GTP-tubulin 1:1 complex, direct evidence has been obtained for GTP- and GDP-P i -microtubule transient states in the early stages of the polymerization process. A simple kinetic analysis of GTP hydrolysis on microtubules within two sequential pseudo-first-order processes led to apparent first-order rate constants of 0.065 s -1 for the cleavage of the γ-phosphate and 0.02 s -1 for the liberation of P i , assuming a simple random model. Apparent rate constants for GTP hydrolysis and P i release were independent of the composition of the buffer used to polymerize tubulin. The significance of these values with respect to those derived from previous studies from this and other laboratories and the possibility of a vectorial model for GTP hydrolysis are discussed

GIT1/βPIX signaling proteins and PAK1 kinase regulate microtubule nucleation.

Science.gov (United States)

Černohorská, Markéta; Sulimenko, Vadym; Hájková, Zuzana; Sulimenko, Tetyana; Sládková, Vladimíra; Vinopal, Stanislav; Dráberová, Eduarda; Dráber, Pavel

2016-06-01

Microtubule nucleation from γ-tubulin complexes, located at the centrosome, is an essential step in the formation of the microtubule cytoskeleton. However, the signaling mechanisms that regulate microtubule nucleation in interphase cells are largely unknown. In this study, we report that γ-tubulin is in complexes containing G protein-coupled receptor kinase-interacting protein 1 (GIT1), p21-activated kinase interacting exchange factor (βPIX), and p21 protein (Cdc42/Rac)-activated kinase 1 (PAK1) in various cell lines. Immunofluorescence microscopy revealed association of GIT1, βPIX and activated PAK1 with centrosomes. Microtubule regrowth experiments showed that depletion of βPIX stimulated microtubule nucleation, while depletion of GIT1 or PAK1 resulted in decreased nucleation in the interphase cells. These data were confirmed for GIT1 and βPIX by phenotypic rescue experiments, and counting of new microtubules emanating from centrosomes during the microtubule regrowth. The importance of PAK1 for microtubule nucleation was corroborated by the inhibition of its kinase activity with IPA-3 inhibitor. GIT1 with PAK1 thus represent positive regulators, and βPIX is a negative regulator of microtubule nucleation from the interphase centrosomes. The regulatory roles of GIT1, βPIX and PAK1 in microtubule nucleation correlated with recruitment of γ-tubulin to the centrosome. Furthermore, in vitro kinase assays showed that GIT1 and βPIX, but not γ-tubulin, serve as substrates for PAK1. Finally, direct interaction of γ-tubulin with the C-terminal domain of βPIX and the N-terminal domain of GIT1, which targets this protein to the centrosome, was determined by pull-down experiments. We propose that GIT1/βPIX signaling proteins with PAK1 kinase represent a novel regulatory mechanism of microtubule nucleation in interphase cells. Copyright © 2016 Elsevier B.V. All rights reserved.

Measuring and modeling polymer concentration profiles near spindle boundaries argues that spindle microtubules regulate their own nucleation

Science.gov (United States)

Kaye, Bryan; Stiehl, Olivia; Foster, Peter J.; Shelley, Michael J.; Needleman, Daniel J.; Fürthauer, Sebastian

2018-05-01

Spindles are self-organized microtubule-based structures that segregate chromosomes during cell division. The mass of the spindle is controlled by the balance between microtubule turnover and nucleation. The mechanisms that control the spatial regulation of microtubule nucleation remain poorly understood. While previous work found that microtubule nucleators bind to pre-existing microtubules in the spindle, it is still unclear whether this binding regulates the activity of those nucleators. Here we use a combination of experiments and mathematical modeling to investigate this issue. We measured the concentration of microtubules and soluble tubulin in and around the spindle. We found a very sharp decay in the concentration of microtubules at the spindle interface. This is inconsistent with a model in which the activity of nucleators is independent of their association with microtubules but consistent with a model in which microtubule nucleators are only active when bound to pre-existing microtubules. This argues that the activity of microtubule nucleators is greatly enhanced when bound to pre-existing microtubules. Thus, microtubule nucleators are both localized and activated by the microtubules they generate.

Real-time wavelet-based inline banknote-in-bundle counting for cut-and-bundle machines

Science.gov (United States)

Petker, Denis; Lohweg, Volker; Gillich, Eugen; Türke, Thomas; Willeke, Harald; Lochmüller, Jens; Schaede, Johannes

2011-03-01

Automatic banknote sheet cut-and-bundle machines are widely used within the scope of banknote production. Beside the cutting-and-bundling, which is a mature technology, image-processing-based quality inspection for this type of machine is attractive. We present in this work a new real-time Touchless Counting and perspective cutting blade quality insurance system, based on a Color-CCD-Camera and a dual-core Computer, for cut-and-bundle applications in banknote production. The system, which applies Wavelet-based multi-scale filtering is able to count banknotes inside a 100-bundle within 200-300 ms depending on the window size.

Evaluation of Single-Bundle versus Double-Bundle PCL Reconstructions with More Than 10-Year Follow-Up

Directory of Open Access Journals (Sweden)

Masataka Deie

2015-01-01

Full Text Available Background. Posterior cruciate ligament (PCL injuries are not rare in acute knee injuries, and several recent anatomical studies of the PCL and reconstructive surgical techniques have generated improved patient results. Now, we have evaluated PCL reconstructions performed by either the single-bundle or double-bundle technique in a patient group followed up retrospectively for more than 10 years. Methods. PCL reconstructions were conducted using the single-bundle (27 cases or double-bundle (13 cases method from 1999 to 2002. The mean age at surgery was 34 years in the single-bundle group and 32 years in the double-bundle group. The mean follow-up period was 12.5 years. Patients were evaluated by Lysholm scoring, the gravity sag view, and knee arthrometry. Results. The Lysholm score after surgery was 89.1±5.6 points for the single-bundle group and 91.9±4.5 points for the double-bundle group. There was no significant difference between the methods in the side-to-side differences by gravity sag view or knee arthrometer evaluation, although several cases in both groups showed a side-to-side difference exceeding 5 mm by the latter evaluation method. Conclusions. We found no significant difference between single- and double-bundle PCL reconstructions during more than 10 years of follow-up.

Brassinosteroids regulate pavement cell growth by mediating BIN2-induced microtubule stabilization.

Science.gov (United States)

Liu, Xiaolei; Yang, Qin; Wang, Yuan; Wang, Linhai; Fu, Ying; Wang, Xuelu

2018-02-23

Brassinosteroids (BRs), a group of plant steroid hormones, play important roles in regulating plant development. The cytoskeleton also affects key developmental processes and a deficiency in BR biosynthesis or signaling leads to abnormal phenotypes similar to those of microtubule-defective mutants. However, how BRs regulate microtubule and cell morphology remains unknown. Here, using liquid chromatography-tandem mass spectrometry, we identified tubulin proteins that interact with Arabidopsis BRASSINOSTEROID INSENSITIVE2 (BIN2), a negative regulator of BR responses in plants. In vitro and in vivo pull-down assays confirmed that BIN2 interacts with tubulin proteins. High-speed co-sedimentation assays demonstrated that BIN2 also binds microtubules. The Arabidopsis genome also encodes two BIN2 homologs, BIN2-LIKE 1 (BIL1) and BIL2, which function redundantly with BIN2. In the bin2-3 bil1 bil2 triple mutant, cortical microtubules were more sensitive to treatment with the microtubule-disrupting drug oryzalin than in wild-type, whereas in the BIN2 gain-of-function mutant bin2-1, cortical microtubules were insensitive to oryzalin treatment. These results provide important insight into how BR regulates plant pavement cell and leaf growth by mediating the stabilization of microtubules by BIN2.

Complementary activities of TPX2 and chTOG constitute an efficient importin-regulated microtubule nucleation module.

Science.gov (United States)

Roostalu, Johanna; Cade, Nicholas I; Surrey, Thomas

2015-11-01

Spindle assembly and function require precise control of microtubule nucleation and dynamics. The chromatin-driven spindle assembly pathway exerts such control locally in the vicinity of chromosomes. One of the key targets of this pathway is TPX2. The molecular mechanism of how TPX2 stimulates microtubule nucleation is not understood. Using microscopy-based dynamic in vitro reconstitution assays with purified proteins, we find that human TPX2 directly stabilizes growing microtubule ends and stimulates microtubule nucleation by stabilizing early microtubule nucleation intermediates. Human microtubule polymerase chTOG (XMAP215/Msps/Stu2p/Dis1/Alp14 homologue) only weakly promotes nucleation, but acts synergistically with TPX2. Hence, a combination of distinct and complementary activities is sufficient for efficient microtubule formation in vitro. Importins control the efficiency of the microtubule nucleation by selectively blocking the interaction of TPX2 with microtubule nucleation intermediates. This in vitro reconstitution reveals the molecular mechanism of regulated microtubule formation by a minimal nucleation module essential for chromatin-dependent microtubule nucleation in cells.

Stable and dynamic microtubules coordinately shape the myosin activation zone during cytokinetic furrow formation

Science.gov (United States)

Foe, Victoria E.; von Dassow, George

2008-01-01

The cytokinetic furrow arises from spatial and temporal regulation of cortical contractility. To test the role microtubules play in furrow specification, we studied myosin II activation in echinoderm zygotes by assessing serine19-phosphorylated regulatory light chain (pRLC) localization after precisely timed drug treatments. Cortical pRLC was globally depressed before cytokinesis, then elevated only at the equator. We implicated cell cycle biochemistry (not microtubules) in pRLC depression, and differential microtubule stability in localizing the subsequent myosin activation. With no microtubules, pRLC accumulation occurred globally instead of equatorially, and loss of just dynamic microtubules increased equatorial pRLC recruitment. Nocodazole treatment revealed a population of stable astral microtubules that formed during anaphase; among these, those aimed toward the equator grew longer, and their tips coincided with cortical pRLC accumulation. Shrinking the mitotic apparatus with colchicine revealed pRLC suppression near dynamic microtubule arrays. We conclude that opposite effects of stable versus dynamic microtubules focuses myosin activation to the cell equator during cytokinesis. PMID:18955555

Katanin: A Sword Cutting Microtubules for Cellular, Developmental, and Physiological Purposes

Directory of Open Access Journals (Sweden)

Ivan Luptovčiak

2017-11-01

Full Text Available KATANIN is a well-studied microtubule severing protein affecting microtubule organization and dynamic properties in higher plants. By regulating mitotic and cytokinetic and cortical microtubule arrays it is involved in the progression of cell division and cell division plane orientation. KATANIN is also involved in cell elongation and morphogenesis during plant growth. In this way KATANIN plays critical roles in diverse plant developmental processes including the development of pollen, embryo, seed, meristem, root, hypocotyl, cotyledon, leaf, shoot, and silique. KATANIN-dependent microtubule regulation seems to be under the control of plant hormones. This minireview provides an overview on available KATANIN mutants and discusses advances in our understanding of KATANIN biological roles in plants.

Co-Higgs bundles on P^1

OpenAIRE

Rayan, Steven

2010-01-01

Co-Higgs bundles are Higgs bundles in the sense of Simpson, but with Higgs fields that take values in the tangent bundle instead of the cotangent bundle. Given a vector bundle on P^1, we find necessary and sufficient conditions on its Grothendieck splitting for it to admit a stable Higgs field. We characterize the rank-2, odd-degree moduli space as a universal elliptic curve with a globally-defined equation. For ranks r=2,3,4, we explicitly verify the conjectural Betti numbers emerging from t...

Short Linear Sequence Motif LxxPTPh Targets Diverse Proteins to Growing Microtubule Ends

NARCIS (Netherlands)

Kumar, Anil; Manatschal, Cristina; Rai, Ankit; Grigoriev, Ilya; Degen, Miriam Steiner; Jaussi, Rolf; Kretzschmar, Ines; Prota, Andrea E; Volkmer, Rudolf; Kammerer, Richard A.; Akhmanova, Anna; Steinmetz, Michel O.

2017-01-01

Microtubule plus-end tracking proteins (+TIPs) are involved in virtually all microtubule-based processes. End-binding (EB) proteins are considered master regulators of +TIP interaction networks, since they autonomously track growing microtubule ends and recruit a plethora of proteins to this

Impact of bundle deformation on CHF: ASSERT-PV assessment of extended burnup Bruce B bundle G85159W

International Nuclear Information System (INIS)

Rao, Y.F.; Manzer, A.M.

2005-01-01

This paper presents a subchannel thermalhydraulic analysis of the effect on critical heat flux (CHF) of bundle deformation such as element bow and diametral creep. The bundle geometry is based on the post-irradiation examination (PIE) data of a single bundle from the Bruce B Nuclear Generating Station, Bruce B bundle G85159W, which was irradiated for more than two years in the core during reactor commissioning. The subchannel code ASSERT-PV IST is used to assess changes in CHF and dryout power due to bundle deformation, compared to the reference, undeformed bundle. (author)

Fluid structure interaction in tube bundles

International Nuclear Information System (INIS)

Brochard, D.; Jedrzejewski, F.; Gibert, R.J.

1995-01-01

A lot of industrial components contain tube bundles immersed in a fluid. The mechanical analysis of such systems requires the study of the fluid structure interaction in the tube bundle. Simplified methods, based on homogenization methods, have been developed to analyse such phenomenon and have been validated through experimental results. Generally, these methods consider only the fluid motion in a plan normal to the bundle axis. This paper will analyse, in a first part, the fluid structure interaction in a tube bundle through a 2D finite element model representing the bundle cross section. The influence of various parameters like the bundle size, and the bundle confinement will be studied. These results will be then compared with results from homogenization methods. Finally, the influence of the 3D fluid motion will be investigated, in using simplified methods. (authors). 11 refs., 12 figs., 2 tabs

Structural analysis of the role of TPX2 in branching microtubule nucleation

Science.gov (United States)

Thawani, Akanksha

2017-01-01

The mitotic spindle consists of microtubules (MTs), which are nucleated by the γ-tubulin ring complex (γ-TuRC). How the γ-TuRC gets activated at the right time and location remains elusive. Recently, it was uncovered that MTs nucleate from preexisting MTs within the mitotic spindle, which requires the protein TPX2, but the mechanism basis for TPX2 action is unknown. Here, we investigate the role of TPX2 in branching MT nucleation. We establish the domain organization of Xenopus laevis TPX2 and define the minimal TPX2 version that stimulates branching MT nucleation, which we find is unrelated to TPX2’s ability to nucleate MTs in vitro. Several domains of TPX2 contribute to its MT-binding and bundling activities. However, the property necessary for TPX2 to induce branching MT nucleation is contained within newly identified γ-TuRC nucleation activator motifs. Separation-of-function mutations leave the binding of TPX2 to γ-TuRC intact, whereas branching MT nucleation is abolished, suggesting that TPX2 may activate γ-TuRC to promote branching MT nucleation. PMID:28264915

Entropy for frame bundle systems and Grassmann bundle systems induced by a diffeomorphism

Institute of Scientific and Technical Information of China (English)

SUN; Weniang(孙文祥)

2002-01-01

ALiao hyperbolic diffeomorphism has equal measure entropy and topological entropy to that ofits induced systems on frame bundles and Grassmann bundles. This solves a problem Liao posed in 1996 forLiao hyperbolic diffeomorphisms.

Template-free electrosynthesis of aligned poly(p-phenylene) microtubules

Institute of Scientific and Technical Information of China (English)

无

2003-01-01

Poly(p-phenylene) (PPP) microtubules with diameters of 0.2-0.8μm and lengths of～10 (m have been synthesized by direct oxidation of benzene in the mixed electrolyte of boron trifluoride diethyl etherate (BFEE) and trifluoroacetic acid (TFA) (BFEE:TFA= 2:1, by volume), containing a certain amount of sodium dodecylbenzene- sulfonate (SDBS) as surfactant. The microtubules were grown vertically on the working electrode surface. The tubular morphology has been confirmed by scanning and transmission electron microscopies and the chain structure of the skin of the tubules has been characterized by Raman spectroscopy. The electrode property, monomer/surfactant molar ratio and the value of applied potential have strong effects on the morphology of the microtubules.

Stabilizing versus Destabilizing the Microtubules: A Double-Edge Sword for an Effective Cancer Treatment Option?

Directory of Open Access Journals (Sweden)

Daniele Fanale

2015-01-01

Full Text Available Microtubules are dynamic and structural cellular components involved in several cell functions, including cell shape, motility, and intracellular trafficking. In proliferating cells, they are essential components in the division process through the formation of the mitotic spindle. As a result of these functions, tubulin and microtubules are targets for anticancer agents. Microtubule-targeting agents can be divided into two groups: microtubule-stabilizing, and microtubule-destabilizing agents. The former bind to the tubulin polymer and stabilize microtubules, while the latter bind to the tubulin dimers and destabilize microtubules. Alteration of tubulin-microtubule equilibrium determines the disruption of the mitotic spindle, halting the cell cycle at the metaphase-anaphase transition and, eventually, resulting in cell death. Clinical application of earlier microtubule inhibitors, however, unfortunately showed several limits, such as neurological and bone marrow toxicity and the emergence of drug-resistant tumor cells. Here we review several natural and synthetic microtubule-targeting agents, which showed antitumor activity and increased efficacy in comparison to traditional drugs in various preclinical and clinical studies. Cryptophycins, combretastatins, ombrabulin, soblidotin, D-24851, epothilones and discodermolide were used in clinical trials. Some of them showed antiangiogenic and antivascular activity and others showed the ability to overcome multidrug resistance, supporting their possible use in chemotherapy.

Signal detection by active, noisy hair bundles

Science.gov (United States)

O'Maoiléidigh, Dáibhid; Salvi, Joshua D.; Hudspeth, A. J.

2018-05-01

Vertebrate ears employ hair bundles to transduce mechanical movements into electrical signals, but their performance is limited by noise. Hair bundles are substantially more sensitive to periodic stimulation when they are mechanically active, however, than when they are passive. We developed a model of active hair-bundle mechanics that predicts the conditions under which a bundle is most sensitive to periodic stimulation. The model relies only on the existence of mechanotransduction channels and an active adaptation mechanism that recloses the channels. For a frequency-detuned stimulus, a noisy hair bundle's phase-locked response and degree of entrainment as well as its detection bandwidth are maximized when the bundle exhibits low-amplitude spontaneous oscillations. The phase-locked response and entrainment of a bundle are predicted to peak as functions of the noise level. We confirmed several of these predictions experimentally by periodically forcing hair bundles held near the onset of self-oscillation. A hair bundle's active process amplifies the stimulus preferentially over the noise, allowing the bundle to detect periodic forces less than 1 pN in amplitude. Moreover, the addition of noise can improve a bundle's ability to detect the stimulus. Although, mechanical activity has not yet been observed in mammalian hair bundles, a related model predicts that active but quiescent bundles can oscillate spontaneously when they are loaded by a sufficiently massive object such as the tectorial membrane. Overall, this work indicates that auditory systems rely on active elements, composed of hair cells and their mechanical environment, that operate on the brink of self-oscillation.

Bundled payment fails to gain a foothold In California: the experience of the IHA bundled payment demonstration.

Science.gov (United States)

Ridgely, M Susan; de Vries, David; Bozic, Kevin J; Hussey, Peter S

2014-08-01

To determine whether bundled payment could be an effective payment model for California, the Integrated Healthcare Association convened a group of stakeholders (health plans, hospitals, ambulatory surgery centers, physician organizations, and vendors) to develop, through a consensus process, the methods and means of implementing bundled payment. In spite of a high level of enthusiasm and effort, the pilot did not succeed in its goal to implement bundled payment for orthopedic procedures across multiple payers and hospital-physician partners. An evaluation of the pilot documented a number of barriers, such as administrative burden, state regulatory uncertainty, and disagreements about bundle definition and assumption of risk. Ultimately, few contracts were signed, which resulted in insufficient volume to test hypotheses about the impact of bundled payment on quality and costs. Although bundled payment failed to gain a foothold in California, the evaluation provides lessons for future bundled payment initiatives. Project HOPE—The People-to-People Health Foundation, Inc.

NAD+ and SIRT3 control microtubule dynamics and reduce susceptibility to antimicrotubule agents

Science.gov (United States)

Harkcom, William T.; Ghosh, Ananda K.; Sung, Matthew S.; Matov, Alexandre; Brown, Kevin D.; Giannakakou, Paraskevi; Jaffrey, Samie R.

2014-01-01

Nicotinamide adenine dinucleotide (NAD+) is an endogenous enzyme cofactor and cosubstrate that has effects on diverse cellular and physiologic processes, including reactive oxygen species generation, mitochondrial function, apoptosis, and axonal degeneration. A major goal is to identify the NAD+-regulated cellular pathways that may mediate these effects. Here we show that the dynamic assembly and disassembly of microtubules is markedly altered by NAD+. Furthermore, we show that the disassembly of microtubule polymers elicited by microtubule depolymerizing agents is blocked by increasing intracellular NAD+ levels. We find that these effects of NAD+ are mediated by the activation of the mitochondrial sirtuin sirtuin-3 (SIRT3). Overexpression of SIRT3 prevents microtubule disassembly and apoptosis elicited by antimicrotubule agents and knockdown of SIRT3 prevents the protective effects of NAD+ on microtubule polymers. Taken together, these data demonstrate that NAD+ and SIRT3 regulate microtubule polymerization and the efficacy of antimicrotubule agents. PMID:24889606

The 5 Clinical Pillars of Value for Total Joint Arthroplasty in a Bundled Payment Paradigm.

Science.gov (United States)

Kim, Kelvin; Iorio, Richard

2017-06-01

Our large, urban, tertiary, university-based institution reflects on its 4-year experience with Bundled Payments for Care Improvement. We will describe the importance of 5 clinical pillars that have contributed to the early success of our bundled payment initiative. We are convinced that value-based care delivered through bundled payment initiatives is the best method to optimize patient outcomes while rewarding surgeons and hospitals for adapting to the evolving healthcare reforms. We summarize a number of experiences and lessons learned since the implementation of Bundled Payments for Care Improvement at our institution. Our experience has led to the development of more refined clinical pathways and coordination of care through evidence-based approaches. We have established that the success of the bundled payment program rests on the following 5 main clinical pillars: (1) optimizing patient selection and comorbidities; (2) optimizing care coordination, patient education, shared decision making, and patient expectations; (3) using a multimodal pain management protocol and minimizing narcotic use to facilitate rapid rehabilitation; (4) optimizing blood management, and standardizing venous thromboembolic disease prophylaxis treatment by risk standardizing patients and minimizing the use of aggressive anticoagulation; and (5) minimizing post-acute facility and resource utilization, and maximizing home resources for patient recovery. From our extensive experience with bundled payment models, we have established 5 clinical pillars of value for bundled payments. Our hope is that these principles will help ease the transition to value-based care for less-experienced healthcare systems. Copyright © 2017 Elsevier Inc. All rights reserved.

Molybdenum-99-producing 37-element fuel bundle neutronically and thermal-hydraulically equivalent to a standard CANDU fuel bundle

Energy Technology Data Exchange (ETDEWEB)

Nichita, E., E-mail: Eleodor.Nichita@uoit.ca; Haroon, J., E-mail: Jawad.Haroon@uoit.ca

2016-10-15

Highlights: • A 37-element fuel bundle modified for {sup 99}Mo production in CANDU reactors is presented. • The modified bundle is neutronically and thermal-hydraulically equivalent to the standard bundle. • The modified bundle satisfies all safety criteria satisfied by the standard bundle. - Abstract: {sup 99m}Tc, the most commonly used radioisotope in diagnostic nuclear medicine, results from the radioactive decay of {sup 99}Mo which is currently being produced at various research reactors around the globe. In this study, the potential use of CANDU power reactors for the production of {sup 99}Mo is investigated. A modified 37-element fuel bundle, suitable for the production of {sup 99}Mo in existing CANDU-type reactors is proposed. The new bundle is specifically designed to be neutronically and thermal-hydraulically equivalent to the standard 37-element CANDU fuel bundle in normal, steady-state operation and, at the same time, be able to produce significant quantities of {sup 99}Mo when irradiated in a CANDU reactor. The proposed bundle design uses fuel pins consisting of a depleted-uranium centre surrounded by a thin layer of low-enriched uranium. The new molybdenum-producing bundle is analyzed using the lattice transport code DRAGON and the diffusion code DONJON. The proposed design is shown to produce 4081 six-day Curies of {sup 99}Mo activity per bundle when irradiated in the peak-power channel of a CANDU core, while maintaining the necessary reactivity and power rating limits. The calculated {sup 99}Mo yield corresponds to approximately one third of the world weekly demand. A production rate of ∼3 bundles per week can meet the global demand of {sup 99}Mo.

Bundling of harvesting residues and whole-trees and the treatment of bundles; Hakkuutaehteiden ja kokopuiden niputus ja nippujen kaesittely

Energy Technology Data Exchange (ETDEWEB)

Kaipainen, H; Seppaenen, V; Rinne, S

1997-12-31

The conditions on which the bundling of the harvesting residues from spruce regeneration fellings would become profitable were studied. The calculations showed that one of the most important features was sufficient compaction of the bundle, so that the portion of the wood in the unit volume of the bundle has to be more than 40 %. The tests showed that the timber grab loader of farm tractor was insufficient for production of dense bundles. The feeding and compression device of the prototype bundler was constructed in the research and with this device the required density was obtained.The rate of compaction of the dry spruce felling residues was about 40 % and that of the fresh residues was more than 50 %. The comparison between the bundles showed that the calorific value of the fresh bundle per unit volume was nearly 30 % higher than that of the dry bundle. This means that the treatment of the bundles should be done of fresh felling residues. Drying of the bundles succeeded well, and the crushing and chipping tests showed that the processing of the bundles at the plant is possible. The treatability of the bundles was also excellent. By using the prototype, developed in the research, it was possible to produce a bundle of the fresh spruce harvesting residues, the diameter of which was about 50 cm and the length about 3 m, and the rate of compaction over 50 %. By these values the reduction target of the costs is obtainable

Bundling of harvesting residues and whole-trees and the treatment of bundles; Hakkuutaehteiden ja kokopuiden niputus ja nippujen kaesittely

Energy Technology Data Exchange (ETDEWEB)

Kaipainen, H.; Seppaenen, V.; Rinne, S.

1996-12-31

The conditions on which the bundling of the harvesting residues from spruce regeneration fellings would become profitable were studied. The calculations showed that one of the most important features was sufficient compaction of the bundle, so that the portion of the wood in the unit volume of the bundle has to be more than 40 %. The tests showed that the timber grab loader of farm tractor was insufficient for production of dense bundles. The feeding and compression device of the prototype bundler was constructed in the research and with this device the required density was obtained.The rate of compaction of the dry spruce felling residues was about 40 % and that of the fresh residues was more than 50 %. The comparison between the bundles showed that the calorific value of the fresh bundle per unit volume was nearly 30 % higher than that of the dry bundle. This means that the treatment of the bundles should be done of fresh felling residues. Drying of the bundles succeeded well, and the crushing and chipping tests showed that the processing of the bundles at the plant is possible. The treatability of the bundles was also excellent. By using the prototype, developed in the research, it was possible to produce a bundle of the fresh spruce harvesting residues, the diameter of which was about 50 cm and the length about 3 m, and the rate of compaction over 50 %. By these values the reduction target of the costs is obtainable

APC and Smad7 link TGFβ type I receptors to the microtubule system to promote cell migration

Science.gov (United States)

Ekman, Maria; Mu, Yabing; Lee, So Young; Edlund, Sofia; Kozakai, Takaharu; Thakur, Noopur; Tran, Hoanh; Qian, Jiang; Groeden, Joanna; Heldin, Carl-Henrik; Landström, Maréne

2012-01-01

Cell migration occurs by activation of complex regulatory pathways that are spatially and temporally integrated in response to extracellular cues. Binding of adenomatous polyposis coli (APC) to the microtubule plus ends in polarized cells is regulated by glycogen synthase kinase 3β (GSK-3β). This event is crucial for establishment of cell polarity during directional migration. However, the role of APC for cellular extension in response to extracellular signals is less clear. Smad7 is a direct target gene for transforming growth factor-β (TGFβ) and is known to inhibit various TGFβ-induced responses. Here we report a new function for Smad7. We show that Smad7 and p38 mitogen–activated protein kinase together regulate the expression of APC and cell migration in prostate cancer cells in response to TGFβ stimulation. In addition, Smad7 forms a complex with APC and acts as an adaptor protein for p38 and GSK-3β kinases to facilitate local TGFβ/p38–dependent inactivation of GSK-3β, accumulation of β-catenin, and recruitment of APC to the microtubule plus end in the leading edge of migrating prostate cancer cells. Moreover, the Smad7–APC complex links the TGFβ type I receptor to the microtubule system to regulate directed cellular extension and migratory responses evoked by TGFβ. PMID:22496417

Vibration of fuel bundles

International Nuclear Information System (INIS)

Chen, S.S.

1975-06-01

Several mathematical models have been proposed for calculating fuel rod responses in axial flows based on a single rod consideration. The spacing between fuel rods in liquid metal fast breeder reactors is small; hence fuel rods will interact with one another due to fluid coupling. The objective of this paper is to study the coupled vibration of fuel bundles. To account for the fluid coupling, a computer code, AMASS, is developed to calculate added mass coefficients for a group of circular cylinders based on the potential flow theory. The equations of motion for rod bundles are then derived including hydrodynamic forces, drag forces, fluid pressure, gravity effect, axial tension, and damping. Based on the equations, a method of analysis is presented to study the free and forced vibrations of rod bundles. Finally, the method is applied to a typical LMFBR fuel bundle consisting of seven rods

Self-Sustained Oscillatory Sliding Movement of Doublet Microtubules and Flagellar Bend Formation.

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Sumio Ishijima

Full Text Available It is well established that the basis for flagellar and ciliary movements is ATP-dependent sliding between adjacent doublet microtubules. However, the mechanism for converting microtubule sliding into flagellar and ciliary movements has long remained unresolved. The author has developed new sperm models that use bull spermatozoa divested of their plasma membrane and midpiece mitochondrial sheath by Triton X-100 and dithiothreitol. These models enable the observation of both the oscillatory sliding movement of activated doublet microtubules and flagellar bend formation in the presence of ATP. A long fiber of doublet microtubules extruded by synchronous sliding of the sperm flagella and a short fiber of doublet microtubules extruded by metachronal sliding exhibited spontaneous oscillatory movements and constructed a one beat cycle of flagellar bending by alternately actuating. The small sliding displacement generated by metachronal sliding formed helical bends, whereas the large displacement by synchronous sliding formed planar bends. Therefore, the resultant waveform is a half-funnel shape, which is similar to ciliary movements.

Potential mechanisms of resistance to microtubule inhibitors.

Science.gov (United States)

Kavallaris, Maria; Annereau, Jean-Philippe; Barret, Jean-Marc

2008-06-01

Antimitotic drugs targeting the microtubules, such as the taxanes and vinca alkaloids, are widely used in the treatment of neoplastic diseases. Development of drug resistance over time, however, limits the efficacy of these agents and poses a clinical challenge to long-term improvement of patient outcomes. Understanding the mechanism(s) of drug resistance becomes paramount to allowing for alternative, if not improved, therapeutic options that might circumvent this challenge. Vinflunine, a novel microtubule inhibitor, has shown superior preclinical antitumor activity, and displays a different pattern of resistance, compared with other agents in the vinca alkaloid class.

Principal noncommutative torus bundles

DEFF Research Database (Denmark)

Echterhoff, Siegfried; Nest, Ryszard; Oyono-Oyono, Herve

2008-01-01

of bivariant K-theory (denoted RKK-theory) due to Kasparov. Using earlier results of Echterhoff and Williams, we shall give a complete classification of principal non-commutative torus bundles up to equivariant Morita equivalence. We then study these bundles as topological fibrations (forgetting the group...

Boiling heat transfer on horizontal tube bundles

International Nuclear Information System (INIS)

Anon.

1987-01-01

Nucleate boiling heat transfer characteristics for a tube in a bundle differ from that for a single tube in a pool and this difference is known as 'tube bundle effect.' There exist two bundle effects, positive and negative. The positive bundle effect enhances heat transfer due to convective flow induced by rising bubbles generated from the lower tubes, while the negative bundle effect deteriorates heat transfer due to vapor blanketing caused by accumulation of bubbles. Staggered tube bundles tested and found that the upper tubes in bundles have higher heat transfer coefficients than the lower tubes. The effects of various parameters such as pressure, tube geometry and oil contamination on heat transfer have been examined. Some workers attempted to clarify the mechanism of occurrence of 'bundle effect' by testing tube arrangements of small scale. All reported only enhancement in heat transfer but results showed the symptom of heat transfer deterioration at higher heat fluxes. As mentioned above, it has not been clarified so far even whether the 'tube bundle effect' should serve as enhancement or deterioration of heat transfer in nucleate boiling. In this study, experiments are performed in detail by using bundles of small scale, and effects of heat flux distribution, pressure and tube location are clarified. Furthermore, some consideration on the mechanisms of occurrence of 'tube bundle effect' is made and a method for prediction of heat transfer rate is proposed

Emerging roles for microtubules in angiosperm pollen tube growth highlight new research cues

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Alessandra eMoscatelli

2015-02-01

Full Text Available In plants, actin filaments have an important role in organelle movement and cytoplasmic streaming. Otherwise microtubules have a role in restricting organelles to specific areas of the cell and in maintaining organelle morphology. In somatic plant cells, microtubules also participate in cell division and morphogenesis, allowing cells to take their definitive shape in order to perform specific functions. In the latter case, microtubules influence assembly of the cell wall, controlling the delivery of enzymes involved in cellulose synthesis and of wall modulation material to the proper sites.In angiosperm pollen tubes, organelle movement is generally attributed to the acto-myosin system, the main role of which is in distributing organelles in the cytoplasm and in carrying secretory vesicles to the apex for polarized growth. Recent data on membrane trafficking suggests a role of microtubules in fine delivery and repositioning of vesicles to sustain pollen tube growth. This review examines the role of microtubules in secretion and endocytosis, highlighting new research cues regarding cell wall construction and pollen tube-pistil crosstalk, that help unravel the role of microtubules in polarized growth.

Electrodynamic effects on microtubules

Czech Academy of Sciences Publication Activity Database

Kučera, Ondřej; Havelka, Daniel; Deriu, M.A.; Cifra, Michal

2015-01-01

Roč. 44, Jul (2015), s. 169-169 ISSN 0175-7571. [10th European-Biophysical-Societies-Association (EBSA) European Biophysics Congress. 18.07.2015-22.07.2015, Dresden] R&D Projects: GA ČR(CZ) GA15-17102S Institutional support: RVO:67985882 Keywords : Microtubules * Electric al polarity Subject RIV: JA - Electronics ; Optoelectronics, Electric al Engineering

Hypothesis: NDL proteins function in stress responses by regulating microtubule organization.

Science.gov (United States)

Khatri, Nisha; Mudgil, Yashwanti

2015-01-01

N-MYC DOWNREGULATED-LIKE proteins (NDL), members of the alpha/beta hydrolase superfamily were recently rediscovered as interactors of G-protein signaling in Arabidopsis thaliana. Although the precise molecular function of NDL proteins is still elusive, in animals these proteins play protective role in hypoxia and expression is induced by hypoxia and nickel, indicating role in stress. Homology of NDL1 with animal counterpart N-MYC DOWNREGULATED GENE (NDRG) suggests similar functions in animals and plants. It is well established that stress responses leads to the microtubule depolymerization and reorganization which is crucial for stress tolerance. NDRG is a microtubule-associated protein which mediates the microtubule organization in animals by causing acetylation and increases the stability of α-tubulin. As NDL1 is highly homologous to NDRG, involvement of NDL1 in the microtubule organization during plant stress can also be expected. Discovery of interaction of NDL with protein kinesin light chain- related 1, enodomembrane family protein 70, syntaxin-23, tubulin alpha-2 chain, as a part of G protein interactome initiative encourages us to postulate microtubule stabilizing functions for NDL family in plants. Our search for NDL interactors in G protein interactome also predicts the role of NDL proteins in abiotic stress tolerance management. Based on published report in animals and predicted interacting partners for NDL in G protein interactome lead us to hypothesize involvement of NDL in the microtubule organization during abiotic stress management in plants.

Cotangent bundle approach to noninertial frames

International Nuclear Information System (INIS)

DeFacio, B.; Retzloff, D.

1980-01-01

The most general possible noninertial acceleration in special relativity is formulated with differential forms in the cotangent bundle. We show that the Lie derivative plays the same role in the cotangent bundle that the covariant derivative plays in the tangent bundle. We also show that a cotangent bundle analog of Fermi--Walker transport can be based upon the, ''cotangent-geodesic'' equation, L/sub u/ω=0. This gives a generalization of the work by Kiehn on classical Hamiltonian mechanics to special relativity

Dynamic release of nuclear RanGTP triggers TPX2-dependent microtubule assembly during the apoptotic execution phase.

Science.gov (United States)

Moss, David K; Wilde, Andrew; Lane, Jon D

2009-03-01

During apoptosis, the interphase microtubule network is dismantled then later replaced by a novel, non-centrosomal microtubule array. These microtubules assist in the peripheral redistribution of nuclear fragments in the apoptotic cell; however, the regulation of apoptotic microtubule assembly is not understood. Here, we demonstrate that microtubule assembly depends upon the release of nuclear RanGTP into the apoptotic cytoplasm because this process is blocked in apoptotic cells overexpressing dominant-negative GDP-locked Ran (T24N). Actin-myosin-II contractility provides the impetus for Ran release and, consequently, microtubule assembly is blocked in blebbistatin- and Y27632-treated apoptotic cells. Importantly, the spindle-assembly factor TPX2 (targeting protein for Xklp2), colocalises with apoptotic microtubules, and siRNA silencing of TPX2, but not of the microtubule motors Mklp1 and Kid, abrogates apoptotic microtubule assembly. These data provide a molecular explanation for the assembly of the apoptotic microtubule network, and suggest important similarities with the process of RanGTP- and TPX2-mediated mitotic spindle formation.

Feeding cells induced by phytoparasitic nematodes require γ-tubulin ring complex for microtubule reorganization.

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Mohamed Youssef Banora

2011-12-01

Full Text Available Reorganization of the microtubule network is important for the fast isodiametric expansion of giant-feeding cells induced by root-knot nematodes. The efficiency of microtubule reorganization depends on the nucleation of new microtubules, their elongation rate and activity of microtubule severing factors. New microtubules in plants are nucleated by cytoplasmic or microtubule-bound γ-tubulin ring complexes. Here we investigate the requirement of γ-tubulin complexes for giant feeding cells development using the interaction between Arabidopsis and Meloidogyne spp. as a model system. Immunocytochemical analyses demonstrate that γ-tubulin localizes to both cortical cytoplasm and mitotic microtubule arrays of the giant cells where it can associate with microtubules. The transcripts of two Arabidopsis γ-tubulin (TUBG1 and TUBG2 and two γ-tubulin complex proteins genes (GCP3 and GCP4 are upregulated in galls. Electron microscopy demonstrates association of GCP3 and γ-tubulin as part of a complex in the cytoplasm of giant cells. Knockout of either or both γ-tubulin genes results in the gene dose-dependent alteration of the morphology of feeding site and failure of nematode life cycle completion. We conclude that the γ-tubulin complex is essential for the control of microtubular network remodelling in the course of initiation and development of giant-feeding cells, and for the successful reproduction of nematodes in their plant hosts.

Validation of an automatic diagnosis of strict left bundle branch block criteria using 12-lead electrocardiograms

DEFF Research Database (Denmark)

Xia, Xiaojuan; Ruwald, Anne-Christine; Ruwald, Martin H

2017-01-01

AIMS: Strict left bundle branch block (LBBB) criteria were recently proposed to identify LBBB patients to benefit most from cardiac resynchronization therapy (CRT). The aim of our study was to automate identification of strict LBBB in order to facilitate its broader application. METHODS: We devel...

Influence of Bundle Diameter and Attachment Point on Kinematic Behavior in Double Bundle Anterior Cruciate Ligament Reconstruction Using Computational Model

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Oh Soo Kwon

2014-01-01

Full Text Available A protocol to choose the graft diameter attachment point of each bundle has not yet been determined since they are usually dependent on a surgeon’s preference. Therefore, the influence of bundle diameters and attachment points on the kinematics of the knee joint needs to be quantitatively analyzed. A three-dimensional knee model was reconstructed with computed tomography images of a 26-year-old man. Based on the model, models of double bundle anterior cruciate ligament (ACL reconstruction were developed. The anterior tibial translations for the anterior drawer test and the internal tibial rotation for the pivot shift test were investigated according to variation of bundle diameters and attachment points. For the model in this study, the knee kinematics after the double bundle ACL reconstruction were dependent on the attachment point and not much influenced by the bundle diameter although larger sized anterior-medial bundles provided increased stability in the knee joint. Therefore, in the clinical setting, the bundle attachment point needs to be considered prior to the bundle diameter, and the current selection method of graft diameters for both bundles appears justified.

A mutation of the fission yeast EB1 overcomes negative regulation by phosphorylation and stabilizes microtubules

International Nuclear Information System (INIS)

Iimori, Makoto; Ozaki, Kanako; Chikashige, Yuji; Habu, Toshiyuki; Hiraoka, Yasushi; Maki, Takahisa; Hayashi, Ikuko; Obuse, Chikashi; Matsumoto, Tomohiro

2012-01-01

Mal3 is a fission yeast homolog of EB1, a plus-end tracking protein (+ TIP). We have generated a mutation (89R) replacing glutamine with arginine in the calponin homology (CH) domain of Mal3. Analysis of the 89R mutant in vitro has revealed that the mutation confers a higher affinity to microtubules and enhances the intrinsic activity to promote the microtubule-assembly. The mutant Mal3 is no longer a + TIP, but binds strongly the microtubule lattice. Live cell imaging has revealed that while the wild type Mal3 proteins dissociate from the tip of the growing microtubules before the onset of shrinkage, the mutant Mal3 proteins persist on microtubules and reduces a rate of shrinkage after a longer pausing period. Consequently, the mutant Mal3 proteins cause abnormal elongation of microtubules composing the spindle and aster. Mal3 is phosphorylated at a cluster of serine/threonine residues in the linker connecting the CH and EB1-like C-terminal motif domains. The phosphorylation occurs in a microtubule-dependent manner and reduces the affinity of Mal3 to microtubules. We propose that because the 89R mutation is resistant to the effect of phosphorylation, it can associate persistently with microtubules and confers a stronger stability of microtubules likely by reinforcing the cylindrical structure. -- Highlights: ► We characterize a mutation (mal3-89R) in fission yeast homolog of EB1. ► The mutation enhances the activity to assemble microtubules. ► Mal3 is phosphorylated in a microtubule-dependent manner. ► The phosphorylation negatively regulates the Mal3 activity.

A mutation of the fission yeast EB1 overcomes negative regulation by phosphorylation and stabilizes microtubules

Energy Technology Data Exchange (ETDEWEB)

Iimori, Makoto; Ozaki, Kanako [Graduate School of Biostudies, Kyoto University, Kitashirakawa-Oiwake cho, Sakyo ku, Kyoto, 606-8502 (Japan); Chikashige, Yuji [Kobe Advanced ICT Research Center, National Institute of Information and Communications Technology, Kobe, 651-2492 (Japan); Habu, Toshiyuki [Graduate School of Biostudies, Kyoto University, Kitashirakawa-Oiwake cho, Sakyo ku, Kyoto, 606-8502 (Japan); Radiation Biology Center, Kyoto University, Yoshida-Konoe cho, Sakyo ku, Kyoto, 606-8501 (Japan); Hiraoka, Yasushi [Kobe Advanced ICT Research Center, National Institute of Information and Communications Technology, Kobe, 651-2492 (Japan); Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, 565-0871 (Japan); Maki, Takahisa; Hayashi, Ikuko [Graduate School of Nanobioscience, Yokohama City University, Tsurumi, Yokohama, 230-0045 (Japan); Obuse, Chikashi [Graduate School of Life Science, Hokkaido University, Sapporo 001-0021 (Japan); Matsumoto, Tomohiro, E-mail: tmatsumo@house.rbc.kyoto-u.ac.jp [Graduate School of Biostudies, Kyoto University, Kitashirakawa-Oiwake cho, Sakyo ku, Kyoto, 606-8502 (Japan); Radiation Biology Center, Kyoto University, Yoshida-Konoe cho, Sakyo ku, Kyoto, 606-8501 (Japan)

2012-02-01

Mal3 is a fission yeast homolog of EB1, a plus-end tracking protein (+ TIP). We have generated a mutation (89R) replacing glutamine with arginine in the calponin homology (CH) domain of Mal3. Analysis of the 89R mutant in vitro has revealed that the mutation confers a higher affinity to microtubules and enhances the intrinsic activity to promote the microtubule-assembly. The mutant Mal3 is no longer a + TIP, but binds strongly the microtubule lattice. Live cell imaging has revealed that while the wild type Mal3 proteins dissociate from the tip of the growing microtubules before the onset of shrinkage, the mutant Mal3 proteins persist on microtubules and reduces a rate of shrinkage after a longer pausing period. Consequently, the mutant Mal3 proteins cause abnormal elongation of microtubules composing the spindle and aster. Mal3 is phosphorylated at a cluster of serine/threonine residues in the linker connecting the CH and EB1-like C-terminal motif domains. The phosphorylation occurs in a microtubule-dependent manner and reduces the affinity of Mal3 to microtubules. We propose that because the 89R mutation is resistant to the effect of phosphorylation, it can associate persistently with microtubules and confers a stronger stability of microtubules likely by reinforcing the cylindrical structure. -- Highlights: Black-Right-Pointing-Pointer We characterize a mutation (mal3-89R) in fission yeast homolog of EB1. Black-Right-Pointing-Pointer The mutation enhances the activity to assemble microtubules. Black-Right-Pointing-Pointer Mal3 is phosphorylated in a microtubule-dependent manner. Black-Right-Pointing-Pointer The phosphorylation negatively regulates the Mal3 activity.

Protein friction limits diffusive and directed movements of kinesin motors on microtubules.

Science.gov (United States)

Bormuth, Volker; Varga, Vladimir; Howard, Jonathon; Schäffer, Erik

2009-08-14

Friction limits the operation of macroscopic engines and is critical to the performance of micromechanical devices. We report measurements of friction in a biological nanomachine. Using optical tweezers, we characterized the frictional drag force of individual kinesin-8 motor proteins interacting with their microtubule tracks. At low speeds and with no energy source, the frictional drag was related to the diffusion coefficient by the Einstein relation. At higher speeds, the frictional drag force increased nonlinearly, consistent with the motor jumping 8 nanometers between adjacent tubulin dimers along the microtubule, and was asymmetric, reflecting the structural polarity of the microtubule. We argue that these frictional forces arise from breaking bonds between the motor domains and the microtubule, and they limit the speed and efficiency of kinesin.

Regulation of developmental and environmental signaling by interaction between microtubules and membranes in plant cells

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Qun Zhang

2015-12-01

Full Text Available ABSTRACT Cell division and expansion require the ordered arrangement of microtubules, which are subject to spatial and temporal modifications by developmental and environmental factors. Understanding how signals translate to changes in cortical microtubule organization is of fundamental importance. A defining feature of the cortical microtubule array is its association with the plasma membrane; modules of the plasma membrane are thought to play important roles in the mediation of microtubule organization. In this review, we highlight advances in research on the regulation of cortical microtubule organization by membrane-associated and membrane-tethered proteins and lipids in response to phytohormones and stress. The transmembrane kinase receptor Rho-like guanosine triphosphatase, phospholipase D, phosphatidic acid, and phosphoinositides are discussed with a focus on their roles in microtubule organization.

CENTROSOMES AND MICROTUBULES DURING MEIOSIS IN THE MUSHROOM BOLETUS RUBINELLUS

Science.gov (United States)

McLaughlin, David J.

1971-01-01

The double centrosome in the basidium of Boletus rubinellus has been observed in three planes with the electron microscope at interphase preceding nuclear fusion, at prophase I, and at interphase I. It is composed of two components connected by a band-shaped middle part. At anaphase I a single, enlarged centrosome is found at the spindle pole, which is attached to the cell membrane. Microtubules mainly oriented parallel to the longitudinal axis of the basidium are present at prefusion, prophase I and interphase I. Cytoplasmic microtubules are absent when the spindle is present. The relationship of the centrosome in B. rubinellus to that in other organisms and the role of the cytoplasmic microtubules are discussed. PMID:4329156

Nanotube bundle oscillators: Carbon and boron nitride nanostructures

International Nuclear Information System (INIS)

Thamwattana, Ngamta; Hill, James M.

2009-01-01

In this paper, we investigate the oscillation of a fullerene that is moving within the centre of a bundle of nanotubes. In particular, certain fullerene-nanotube bundle oscillators, namely C 60 -carbon nanotube bundle, C 60 -boron nitride nanotube bundle, B 36 N 36 -carbon nanotube bundle and B 36 N 36 -boron nitride nanotube bundle are studied using the Lennard-Jones potential and the continuum approach which assumes a uniform distribution of atoms on the surface of each molecule. We address issues regarding the maximal suction energies of the fullerenes which lead to the generation of the maximum oscillation frequency. Since bundles are also found to comprise double-walled nanotubes, this paper also examines the oscillation of a fullerene inside a double-walled nanotube bundle. Our results show that the frequencies obtained for the oscillation within double-walled nanotube bundles are slightly higher compared to those of single-walled nanotube bundle oscillators. Our primary purpose here is to extend a number of established results for carbon to the boron nitride nanostructures.

TBCD links centriologenesis, spindle microtubule dynamics, and midbody abscission in human cells.

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Mónica López Fanarraga

2010-01-01

Full Text Available Microtubule-organizing centers recruit alpha- and beta-tubulin polypeptides for microtubule nucleation. Tubulin synthesis is complex, requiring five specific cofactors, designated tubulin cofactors (TBCs A-E, which contribute to various aspects of microtubule dynamics in vivo. Here, we show that tubulin cofactor D (TBCD is concentrated at the centrosome and midbody, where it participates in centriologenesis, spindle organization, and cell abscission. TBCD exhibits a cell-cycle-specific pattern, localizing on the daughter centriole at G1 and on procentrioles by S, and disappearing from older centrioles at telophase as the protein is recruited to the midbody. Our data show that TBCD overexpression results in microtubule release from the centrosome and G1 arrest, whereas its depletion produces mitotic aberrations and incomplete microtubule retraction at the midbody during cytokinesis. TBCD is recruited to the centriole replication site at the onset of the centrosome duplication cycle. A role in centriologenesis is further supported in differentiating ciliated cells, where TBCD is organized into "centriolar rosettes". These data suggest that TBCD participates in both canonical and de novo centriolar assembly pathways.

Fission yeast cells undergo nuclear division in the absence of spindle microtubules.

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Stefania Castagnetti

2010-10-01

Full Text Available Mitosis in eukaryotic cells employs spindle microtubules to drive accurate chromosome segregation at cell division. Cells lacking spindle microtubules arrest in mitosis due to a spindle checkpoint that delays mitotic progression until all chromosomes have achieved stable bipolar attachment to spindle microtubules. In fission yeast, mitosis occurs within an intact nuclear membrane with the mitotic spindle elongating between the spindle pole bodies. We show here that in fission yeast interference with mitotic spindle formation delays mitosis only briefly and cells proceed to an unusual nuclear division process we term nuclear fission, during which cells perform some chromosome segregation and efficiently enter S-phase of the next cell cycle. Nuclear fission is blocked if spindle pole body maturation or sister chromatid separation cannot take place or if actin polymerization is inhibited. We suggest that this process exhibits vestiges of a primitive nuclear division process independent of spindle microtubules, possibly reflecting an evolutionary intermediate state between bacterial and Archeal chromosome segregation where the nucleoid divides without a spindle and a microtubule spindle-based eukaryotic mitosis.

Mto2 multisite phosphorylation inactivates non-spindle microtubule nucleation complexes during mitosis

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Borek, Weronika E.; Groocock, Lynda M.; Samejima, Itaru; Zou, Juan; de Lima Alves, Flavia; Rappsilber, Juri; Sawin, Kenneth E.

2015-01-01

Microtubule nucleation is highly regulated during the eukaryotic cell cycle, but the underlying molecular mechanisms are largely unknown. During mitosis in fission yeast Schizosaccharomyces pombe, cytoplasmic microtubule nucleation ceases simultaneously with intranuclear mitotic spindle assembly. Cytoplasmic nucleation depends on the Mto1/2 complex, which binds and activates the γ-tubulin complex and also recruits the γ-tubulin complex to both centrosomal (spindle pole body) and non-centrosomal sites. Here we show that the Mto1/2 complex disassembles during mitosis, coincident with hyperphosphorylation of Mto2 protein. By mapping and mutating multiple Mto2 phosphorylation sites, we generate mto2-phosphomutant strains with enhanced Mto1/2 complex stability, interaction with the γ-tubulin complex and microtubule nucleation activity. A mutant with 24 phosphorylation sites mutated to alanine, mto2[24A], retains interphase-like behaviour even in mitotic cells. This provides a molecular-level understanding of how phosphorylation ‘switches off' microtubule nucleation complexes during the cell cycle and, more broadly, illuminates mechanisms regulating non-centrosomal microtubule nucleation. PMID:26243668

Microtubule-targeting drugs rescue axonal swellings in cortical neurons from spastin knockout mice

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Coralie Fassier

2013-01-01

Mutations in SPG4, encoding the microtubule-severing protein spastin, are responsible for the most frequent form of hereditary spastic paraplegia (HSP, a heterogeneous group of genetic diseases characterized by degeneration of the corticospinal tracts. We previously reported that mice harboring a deletion in Spg4, generating a premature stop codon, develop progressive axonal degeneration characterized by focal axonal swellings associated with impaired axonal transport. To further characterize the molecular and cellular mechanisms underlying this mutant phenotype, we have assessed microtubule dynamics and axonal transport in primary cultures of cortical neurons from spastin-mutant mice. We show an early and marked impairment of microtubule dynamics all along the axons of spastin-deficient cortical neurons, which is likely to be responsible for the occurrence of axonal swellings and cargo stalling. Our analysis also reveals that a modulation of microtubule dynamics by microtubule-targeting drugs rescues the mutant phenotype of cortical neurons. Together, these results contribute to a better understanding of the pathogenesis of SPG4-linked HSP and ascertain the influence of microtubule-targeted drugs on the early axonal phenotype in a mouse model of the disease.

Prion protein inhibits microtubule assembly by inducing tubulin oligomerization

International Nuclear Information System (INIS)

Nieznanski, Krzysztof; Podlubnaya, Zoya A.; Nieznanska, Hanna

2006-01-01

A growing body of evidence points to an association of prion protein (PrP) with microtubular cytoskeleton. Recently, direct binding of PrP to tubulin has also been found. In this work, using standard light scattering measurements, sedimentation experiments, and electron microscopy, we show for First time the effect of a direct interaction between these proteins on tubulin polymerization. We demonstrate that full-length recombinant PrP induces a rapid increase in the turbidity of tubulin diluted below the critical concentration for microtubule assembly. This effect requires magnesium ions and is weakened by NaCl. Moreover, the PrP-induced light scattering structures of tubulin are cold-stable. In preparations of diluted tubulin incubated with PrP, electron microscopy revealed the presence of ∼50 nm disc-shaped structures not reported so far. These unique tubulin oligomers may form large aggregates. The effect of PrP is more pronounced under the conditions promoting microtubule formation. In these tubulin samples, PrP induces formation of the above oligomers associated with short protofilaments and sheets of protofilaments into aggregates. Noticeably, this is accompanied by a significant reduction of the number and length of microtubules. Hence, we postulate that prion protein may act as an inhibitor of microtubule assembly by inducing formation of stable tubulin oligomers

EWSR1 regulates mitosis by dynamically influencing microtubule acetylation.

Science.gov (United States)

Wang, Yi-Long; Chen, Hui; Zhan, Yi-Qun; Yin, Rong-Hua; Li, Chang-Yan; Ge, Chang-Hui; Yu, Miao; Yang, Xiao-Ming

2016-08-17

EWSR1, participating in transcription and splicing, has been identified as a translocation partner for various transcription factors, resulting in translocation, which in turn plays crucial roles in tumorigenesis. Recent studies have investigated the role of EWSR1 in mitosis. However, the effect of EWSR1 on mitosis is poorly understood. Here, we observed that depletion of EWSR1 resulted in cell cycle arrest in the mitotic phase, mainly due to an increase in the time from nuclear envelope breakdown to metaphase, resulting in a high percentage of unaligned chromosomes and multipolar spindles. We also demonstrated that EWSR1 is a spindle-associated protein that interacts with α-tubulin during mitosis. EWSR1 depletion increased the cold-sensitivity of spindle microtubules, and decreased the rate of spindle assembly. EWSR1 regulated the level of microtubule acetylation in the mitotic spindle; microtubule acetylation was rescued in EWSR1-depleted mitotic cells following suppression of HDAC6 activity by its specific inhibitor or siRNA treatment. In summary, these results suggest that EWSR1 regulates the acetylation of microtubules in a cell cycle-dependent manner through its dynamic location on spindle MTs, and may be a novel regulator for mitosis progress independent of its translocation.

Holomorphic bundles over elliptic manifolds

International Nuclear Information System (INIS)

Morgan, J.W.

2000-01-01

In this lecture we shall examine holomorphic bundles over compact elliptically fibered manifolds. We shall examine constructions of such bundles as well as (duality) relations between such bundles and other geometric objects, namely K3-surfaces and del Pezzo surfaces. We shall be dealing throughout with holomorphic principal bundles with structure group GC where G is a compact, simple (usually simply connected) Lie group and GC is the associated complex simple algebraic group. Of course, in the special case G = SU(n) and hence GC = SLn(C), we are considering holomorphic vector bundles with trivial determinant. In the other cases of classical groups, G SO(n) or G = Sympl(2n) we are considering holomorphic vector bundles with trivial determinant equipped with a non-degenerate symmetric, or skew symmetric pairing. In addition to these classical cases there are the finite number of exceptional groups. Amazingly enough, motivated by questions in physics, much interest centres around the group E8 and its subgroups. For these applications it does not suffice to consider only the classical groups. Thus, while often first doing the case of SU(n) or more generally of the classical groups, we shall extend our discussions to the general semi-simple group. Also, we shall spend a good deal of time considering elliptically fibered manifolds of the simplest type, namely, elliptic curves

Evaluation of bundle duct interaction by out-of-pile compression test of FBR fuel pin bundles

Energy Technology Data Exchange (ETDEWEB)

Tanaka, Kosuke; Yamamoto, Yuji; Nagamine, Tsuyoshi; Maeda, Koji [Japan Nuclear Cycle Development Inst., Oarai, Ibaraki (Japan). Oarai Engineering Center

2001-06-01

Bundle duct interaction (BDI) caused by expansion of fuel pin bundle is a main factor to limit the fuel lifetime. Therefore, it is important for the design of fast reactor fuel assembly to understand the fuel pin deformation behavior under BDI condition. In order to understand the fuel pin deformation behavior under BDI condition, out-of-pile compression tests were conducted for FBR fuel pin bundle by use of X-ray CT equipment. In these compression tests, two kinds of fuel pin bundles were conducted. One was the fuel pin bundle with the short wire-pitch and the other was the fuel pin bundle with the short wire-pitch and large diameter claddings. The general discussions were also performed based on the results of out-of-pile compression tests obtained by use of X-ray CT equipment in the previous work. Following results were obtained. 1) The occurrence of the pin-to-duct contact depends on the wire-pitch. In the fuel pin bundle with large wire-pitch, the pin-to-duct contact occurred at the early stage of BDI. The reason of this result is due to the low bowing rigidity of the fuel pins with long wire-pitch. 2) The value of the ovalation stiffness strongly depends on the geometry of cladding (diameter, thickness) and especially on wire-pitch. This result in this work revealed that the occurrence of the pin-to-duct contact depends on the value of the ovalation stiffness. 3) The occurrence of wire dispersion and dispersive displacement of pins depends on the wire-pitch strongly. In the fuel pin bundle with the long wire-pitch, the occurrence of the above-mentioned suppression mechanism to BDI is remarkable. 4) The suppression mechanism to BDI of the fuel pin bundle with the long wire-pitch is elastic oval deformation of cladding, wire dispersion and dispersive displacement of pins. On the other hand, the elastic and plastic oval deformation of cladding is the major suppression mechanism to BDI in the fuel pin bundle with the short wire-pitch. 5) The appearance of

Muon bundles from the Universe

Directory of Open Access Journals (Sweden)

Kankiewicz P.

2018-01-01

Full Text Available Recently the CERN ALICE experiment, in its dedicated cosmic ray run, observed muon bundles of very high multiplicities, thereby confirming similar findings from the LEP era at CERN (in the CosmoLEP project. Significant evidence for anisotropy of arrival directions of the observed high multiplicity muonic bundles is found. Estimated directionality suggests their possible extragalactic provenance. We argue that muonic bundles of highest multiplicity are produced by strangelets, hypothetical stable lumps of strange quark matter infiltrating our Universe.

Infinitesimal bundles and projective relativity

International Nuclear Information System (INIS)

Evans, G.T.

1973-01-01

An intrinsic and global presentation of five-dimensional relativity theory is developed, in which special coordinate conditions are replaced by conditions of Lie invariance. The notion of an infinitesimal bundle is introduced, and the theory of connexions on principal bundles is extended to infinitesimal bundles. Global aspects of projective relativity are studied: it is shown that projective relativity can describe almost any space-time. In particular, it is not necessary to assume that the electromagnetic field have a global potential. (author)

Dietary flavonoid fisetin binds to β-tubulin and disrupts microtubule dynamics in prostate cancer cells.

Science.gov (United States)

Mukhtar, Eiman; Adhami, Vaqar Mustafa; Sechi, Mario; Mukhtar, Hasan

2015-10-28

Microtubule targeting based therapies have revolutionized cancer treatment; however, resistance and side effects remain a major limitation. Therefore, novel strategies that can overcome these limitations are urgently needed. We made a novel discovery that fisetin, a hydroxyflavone, is a microtubule stabilizing agent. Fisetin binds to tubulin and stabilizes microtubules with binding characteristics far superior than paclitaxel. Surface plasmon resonance and computational docking studies suggested that fisetin binds to β-tubulin with superior affinity compared to paclitaxel. Fisetin treatment of human prostate cancer cells resulted in robust up-regulation of microtubule associated proteins (MAP)-2 and -4. In addition, fisetin treated cells were enriched in α-tubulin acetylation, an indication of stabilization of microtubules. Fisetin significantly inhibited PCa cell proliferation, migration, and invasion. Nudc, a protein associated with microtubule motor dynein/dynactin complex that regulates microtubule dynamics, was inhibited with fisetin treatment. Further, fisetin treatment of a P-glycoprotein overexpressing multidrug-resistant cancer cell line NCI/ADR-RES inhibited the viability and colony formation. Our results offer in vitro proof-of-concept for fisetin as a microtubule targeting agent. We suggest that fisetin could be developed as an adjuvant for treatment of prostate and other cancer types. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

CANFLEX fuel bundle strength tests (test report)

International Nuclear Information System (INIS)

Chang, Seok Kyu; Chung, C. H.; Kim, B. D.

1997-08-01

This document outlines the test results for the strength tests of the CANFLEX fuel bundle. Strength tests are performed to determine and verify the amount of the bundle shape distortion which is against the side-stops when the bundles are refuelling. There are two cases of strength test; one is the double side-stop test which simulates the normal bundle refuelling and the other is the single side-stop test which simulates the abnormal refuelling. the strength test specification requires that the fuel bundle against the side-stop(s) simulators for this test were fabricated and the flow rates were controlled to provide the required conservative hydraulic forces. The test rig conditions of 120 deg C, 11.2 MPa were retained for 15 minutes after the flow rate was controlled during the test in two cases, respectively. The bundle loading angles of number 13- number 15 among the 15 bundles were 67.5 deg CCW and others were loaded randomly. After the tests, the bundle shapes against the side-stops were measured and inspected carefully. The important test procedures and measurements were discussed as follows. (author). 5 refs., 22 tabs., 5 figs

FACILITATING RADICAL FRONT-END INNOVATION THROUGH TARGETED HR PRACTICES

DEFF Research Database (Denmark)

Aagaard, Annabeth

2017-01-01

This study examines how radical front end innovation can be actively facilitated through selected and targeted HR practices and bundles of HR practices. The empirical field is an explorative case study of front end innovation and HR practices in the pharmaceutical industry, with an in-depth case ...

The Comparison Analysis of Thermalhydraulic Behavior Between A Reference 37-element Bundle and A Modified 37-element Bundle

International Nuclear Information System (INIS)

Ryu, Eui-Seung; You, Sung-Chang

2014-01-01

As pressure tube diameter creep increase, the coolant flows through some of the interior subchannels of the fuel bundle are reduced and consequently reduces the Critical Heat Flux (CHF). For this reason, Canadian Utilities have performed the project that developing the new fuel design (modified 37-element bundle) to increase critical heat flux. The modified 37-element (37M) bundle has the same overall geometry as the reference 37-element (37R) bundle that is using in the Wolsong units now but the center element diameter has been reduced from 13.06mm to 11.5mm. The reduction in center element diameter of the 37M bundle design increase the flow of center areas to improve the cooling and thus to enhance CHF. The CHF experiments with 37M bundle string simulator in un-crept and crept (3.3%, 5.1% peak creep) flow channels were completed at Stern Laboratories in 2008. A substantially large increase in dryout-power was observed for the 37M bundle compared to the 37R bundle, particularly in the 5.1% crept channel. As a result of the experiments, Ontario Power Generation (OPG) and Bruce Power (BP) have increased the operational margin with this CHF correlation and has fully refueled the 37M fuel on some units or almost done on the other units. KHNP also has performed the project to refuel the 37M bundle which is the same design with OPG and BP recently. This paper summarizes the comparison assessment of Thermalhydraulic (T/H) behavior for 37M bundle and 37R bundle with their own correlations and geometry parameters. This analysis performed with the thermal hydraulic code (NUCIRC) and the site measured data at the Wolsong Unit2. Tests to evaluate the CHF performance with the 37M fuel bundle have been conducted in 2008 using the un-crept, 3.3% crept and 5.1% crept flow channels in the CHF Test facility at Stern Laboratories. In addition pressure drop tests have been performed at the same time. The changes of geometry from 37R bundle to 37M bundle reduced the center element

Fiber bundles in non-relativistic quantum mechanics

International Nuclear Information System (INIS)

Moylan, P.

1979-11-01

The problem of describing a quantum-mechanical system with symmetry by a fiber bundle is considered. The quantization of a fiber bundle is introduced. Fiber bundles for the Kepler problem and the rotator are constructed. The fiber bundle concept provides a new model for a physical system: it provides a model for an elementary particle with extension having integral values of spin. 5 figures

Twisted Vector Bundles on Pointed Nodal Curves

Indian Academy of Sciences (India)

Abstract. Motivated by the quest for a good compactification of the moduli space of -bundles on a nodal curve we establish a striking relationship between Abramovich's and Vistoli's twisted bundles and Gieseker vector bundles.

Effects of ultraviolet radiation on microtubule organisation and morphogenesis in plants

International Nuclear Information System (INIS)

Staxen, I.

1994-09-01

The involvement of the cytoskeleton in the development of somatic embryos was studied in Larix x eurolepis. Protoplasts were isolated from both somatic embryo-regenerating and non-generating cultures and fractionated on a discontinuous Percoll density gradient, whereby a highly embryogenic protoplast fraction could be enriched. Protoplasts of two cell lines of Larix eurolepis, one with regenerating potential and one lacking this potential, were compared. In contrast to the non-regenerating line were a protoplast-like organisation of the cortical microtubules was maintained, re-organisation of this microtubular network occurred in the regenerable line after only three days of culture, indicating that organised growth was occurring. However, this early organisation of cortical microtubules may not always be a valid marker for regenerable and non-regenerable material. In order to investigate the effect of ultraviolet-B (UV-B, 280-320 nm) radiation on the microtubule cytoskeleton, protoplasts were isolated from leaves of Petunia hybrida and subjected to four different doses of UV-B radiation. The organisation of the microtubules and the progression of the cells through the cell cycle was observed at 0, 24, 48 and 72 h after irradiation. UV-B induced breaks in the cortical microtubules resulting in shorter fragments with increasing amounts of radiation. Also, the division of the protoplasts was delayed, which was related to the absence of an microtubule network. Whole Petunia plants were grown in growth chambers in the presence and absence of UV-B. The plants responded to UV-B with increased rates of CO 2 assimilation, a 60% increase in UV-screening compounds and the changes in the morphology of the leaves that were reflected in a 70-100% increase in leaf area and 20% decrease in leaf thickness. The microtubules of the epidermal cells was not affected by UV-B, nor was the number of epidermal cells (per unit area). The increase in leaf area in the UV-treated plants

The Drosophila Microtubule-Associated Protein Mars Stabilizes Mitotic Spindles by Crosslinking Microtubules through Its N-Terminal Region

Science.gov (United States)

Zhang, Gang; Beati, Hamze; Nilsson, Jakob; Wodarz, Andreas

2013-01-01

Correct segregation of genetic material relies on proper assembly and maintenance of the mitotic spindle. How the highly dynamic microtubules (MTs) are maintained in stable mitotic spindles is a key question to be answered. Motor and non-motor microtubule associated proteins (MAPs) have been reported to stabilize the dynamic spindle through crosslinking adjacent MTs. Mars, a novel MAP, is essential for the early development of Drosophila embryos. Previous studies showed that Mars is required for maintaining an intact mitotic spindle but did not provide a molecular mechanism for this function. Here we show that Mars is able to stabilize the mitotic spindle in vivo. Both in vivo and in vitro data reveal that the N-terminal region of Mars functions in the stabilization of the mitotic spindle by crosslinking adjacent MTs. PMID:23593258

The Drosophila microtubule-associated protein mars stabilizes mitotic spindles by crosslinking microtubules through its N-terminal region.

Directory of Open Access Journals (Sweden)

Gang Zhang

Full Text Available Correct segregation of genetic material relies on proper assembly and maintenance of the mitotic spindle. How the highly dynamic microtubules (MTs are maintained in stable mitotic spindles is a key question to be answered. Motor and non-motor microtubule associated proteins (MAPs have been reported to stabilize the dynamic spindle through crosslinking adjacent MTs. Mars, a novel MAP, is essential for the early development of Drosophila embryos. Previous studies showed that Mars is required for maintaining an intact mitotic spindle but did not provide a molecular mechanism for this function. Here we show that Mars is able to stabilize the mitotic spindle in vivo. Both in vivo and in vitro data reveal that the N-terminal region of Mars functions in the stabilization of the mitotic spindle by crosslinking adjacent MTs.

The Drosophila microtubule-associated protein mars stabilizes mitotic spindles by crosslinking microtubules through its N-terminal region.

Science.gov (United States)

Zhang, Gang; Beati, Hamze; Nilsson, Jakob; Wodarz, Andreas

2013-01-01

Correct segregation of genetic material relies on proper assembly and maintenance of the mitotic spindle. How the highly dynamic microtubules (MTs) are maintained in stable mitotic spindles is a key question to be answered. Motor and non-motor microtubule associated proteins (MAPs) have been reported to stabilize the dynamic spindle through crosslinking adjacent MTs. Mars, a novel MAP, is essential for the early development of Drosophila embryos. Previous studies showed that Mars is required for maintaining an intact mitotic spindle but did not provide a molecular mechanism for this function. Here we show that Mars is able to stabilize the mitotic spindle in vivo. Both in vivo and in vitro data reveal that the N-terminal region of Mars functions in the stabilization of the mitotic spindle by crosslinking adjacent MTs.

Mathematical modeling of alignment dynamics in active motor-filament systems

Science.gov (United States)

Swaminathan, Sumanth

The formation of the cytoskeleton, via motor-mediated microtubule self-organization, is an important subject of study in the biological sciences as well as in nonequilibrium, soft matter physics. Accurate modeling of the dynamics is a formidable task as it involves intrinsic nonlinearities, structural anisotropies, nonequilibrium processes, and a broad window of time scales, length scales, and densities. In this thesis, we study the ordering dynamics and pattern formations arising from motor-mediated microtubule self-organization in dilute and semi-dilute filament solutions. In the dilute case, we use a probabilistic model in which microtubules interact through motor induced, inelastic binary collisions. This model shows that initially disordered filament solutions exhibit an ordering transition resulting in the emergence of well aligned rod bundles. We study the existence and dynamic interaction of microtubule bundles analytically and numerically. Our results show a long term attraction and coalescing of bundles indicating a clear coarsening in the system; microtubule bundles concentrate into fewer orientations on a slow logarithmic time scale. In the semi-dilute case, multiple motors can bind a filament to several others and, for a critical motor density, induce a transition to an ordered state with a nonzero mean orientation. We develop a spatially homogeneous, mean-field theory that explicitly accounts for motor forcing and thermal fluctuations which enter into the model as multiplicative and additive noises respectively. Our model further incorporates a force-dependent detachment rate of motors, which in turn affects the mean and the fluctuations of the net force acting on a filament. We demonstrate that the transition to the oriented state changes from second order to first order when the force-dependent detachment becomes important. In our final analysis, we add complex spatial inhomogeneities to our mean field theory. The revised model consists of a system

Survivin counteracts the therapeutic effect of microtubule de-stabilizers by stabilizing tubulin polymers

Directory of Open Access Journals (Sweden)

Hsieh Hsing-Pang

2009-07-01

Full Text Available Abstract Background Survivin is a dual function protein. It inhibits the apoptosis of cells by inhibiting caspases, and also promotes cell growth by stabilizing microtubules during mitosis. Over-expression of survivin has been demonstrated to induce drug-resistance to various chemo-therapeutic agents such as cisplatin (DNA damaging agent and paclitaxel (microtubule stabilizer in cancers. However, survivin-induced resistance to microtubule de-stabilizers such as Vinca alkaloids and Combretastatin A-4 (CA-4-related compounds were seldom demonstrated in the past. Furthermore, the question remains as to whether survivin plays a dominant role in processing cytokinesis or inhibiting caspases activity in cells treated with anti-mitotic compounds. The purpose of this study is to evaluate the effect of survivin on the resistance and susceptibility of human cancer cells to microtubule de-stabilizer-induced cell death. Results BPR0L075 is a CA-4 analog that induces microtubule de-polymerization and subsequent caspase-dependent apoptosis. To study the relationship between the expression of survivin and the resistance to microtubule de-stabilizers, a KB-derived BPR0L075-resistant cancer cell line, KB-L30, was generated for this study. Here, we found that survivin was over-expressed in the KB-L30 cells. Down-regulation of survivin by siRNA induced hyper-sensitivity to BPR0L075 in KB cells and partially re-stored sensitivity to BPR0L075 in KB-L30 cells. Western blot analysis revealed that down-regulation of survivin induced microtubule de-stabilization in both KB and KB-L30 cells. However, the same treatment did not enhance the down-stream caspase-3/-7 activities in BPR0L075-treated KB cells. Translocation of a caspase-independent apoptosis-related molecule, apoptosis-inducing factor (AIF, from cytoplasm to the nucleus was observed in survivin-targeted KB cells under BPR0L075 treatment. Conclusion In this study, survivin plays an important role in the

Preliminary report: NIF laser bundle review

International Nuclear Information System (INIS)

Tietbohl, G.L.; Larson, D.W.; Erlandson, A.C.

1995-01-01

As requested in the guidance memo 1 , this committe determined whether there are compelling reasons to recommend a change from the NIF CDR baseline laser. The baseline bundle design based on a tradeoff between cost and technical risk, which is replicated four times to create the required 192 beams. The baseline amplifier design uses bottom loading 1x4 slab and flashlamp cassettes for amplifier maintenance and large vacuum enclosures (2.5m high x 7m wide in cross-section for each of the two spatial filters in each of the four bundles. The laser beams are arranged in two laser bays configured in a u-shape around the target area. The entire bundle review effort was performed in a very short time (six weeks) and with limited resources (15 personnel part-time). This should be compared to the effort that produced the CDR design (12 months, 50 to 100 personnel). This committee considered three alternate bundle configurations (2x2, 4x2, and 4x4 bundles), and evaluated each bundle against the baseline design using the seven requested issues in the guidance memo: Cost; schedule; performance risk; maintainability/operability; hardware failure cost exposure; activation; and design flexibility. The issues were reviewed to identify differences between each alternate bundle configuration and the baseline

Warps, grids and curvature in triple vector bundles

Science.gov (United States)

Flari, Magdalini K.; Mackenzie, Kirill

2018-06-01

A triple vector bundle is a cube of vector bundle structures which commute in the (strict) categorical sense. A grid in a triple vector bundle is a collection of sections of each bundle structure with certain linearity properties. A grid provides two routes around each face of the triple vector bundle, and six routes from the base manifold to the total manifold; the warps measure the lack of commutativity of these routes. In this paper we first prove that the sum of the warps in a triple vector bundle is zero. The proof we give is intrinsic and, we believe, clearer than the proof using decompositions given earlier by one of us. We apply this result to the triple tangent bundle T^3M of a manifold and deduce (as earlier) the Jacobi identity. We further apply the result to the triple vector bundle T^2A for a vector bundle A using a connection in A to define a grid in T^2A . In this case the curvature emerges from the warp theorem.

The effects of 60Co γ-ray irradiation on cytoplasmic microtubules of mouse macrophages and lymphocytes

International Nuclear Information System (INIS)

Li Qianqian; Mao Zijun; Yin Zhiwei; Hu Yumin

1989-05-01

The effects of 60 Co γ-ray irradiation on cytoplasmic microtubules of mouse macrophages and lymphocytes were investigated by immunofluorescence microscopy and scanning electron microscope. The results indicated. (1) microtubule organization of the irradiated cells remarkably differed from that of the control since the doses over 4 Gy; (2) 144 hours after irradiation the alterations of microtubules have been shown to be basically r epaired ; (3) the cytoplasmic microtubules and centrioles disappeared under transmission electron microscope, the membranes irradiated and microvilli showed changes under scanning electron microscope too. From these observations and those of other workers who studied the radiation effect on extracted microtubule proteins in vitro, the authors support that 60 Co γ-ray irradiation can inhabits cytoplasmic microtubule assembling

Learning-induced and stathmin-dependent changes in microtubule stability are critical for memory and disrupted in ageing

Science.gov (United States)

Uchida, Shusaku; Martel, Guillaume; Pavlowsky, Alice; Takizawa, Shuichi; Hevi, Charles; Watanabe, Yoshifumi; Kandel, Eric R.; Alarcon, Juan Marcos; Shumyatsky, Gleb P.

2014-01-01

Changes in the stability of microtubules regulate many biological processes, but their role in memory remains unclear. Here we show that learning causes biphasic changes in the microtubule-associated network in the hippocampus. In the early phase, stathmin is dephosphorylated, enhancing its microtubule-destabilizing activity by promoting stathmin-tubulin binding, whereas in the late phase these processes are reversed leading to an increase in microtubule/KIF5-mediated localization of the GluA2 subunit of AMPA receptors at synaptic sites. A microtubule stabilizer paclitaxel decreases or increases memory when applied at the early or late phases, respectively. Stathmin mutations disrupt changes in microtubule stability, GluA2 localization, synaptic plasticity and memory. Aged wild-type mice show impairments in stathmin levels, changes in microtubule stability, and GluA2 localization. Blocking GluA2 endocytosis rescues memory deficits in stathmin mutant and aged wild-type mice. These findings demonstrate a role for microtubules in memory in young adult and aged individuals. PMID:25007915

Interactive domains in the molecular chaperone human alphaB crystallin modulate microtubule assembly and disassembly.

Directory of Open Access Journals (Sweden)

Joy G Ghosh

2007-06-01

Full Text Available Small heat shock proteins regulate microtubule assembly during cell proliferation and in response to stress through interactions that are poorly understood.Novel functions for five interactive sequences in the small heat shock protein and molecular chaperone, human alphaB crystallin, were investigated in the assembly/disassembly of microtubules and aggregation of tubulin using synthetic peptides and mutants of human alphaB crystallin.The interactive sequence (113FISREFHR(120 exposed on the surface of alphaB crystallin decreased microtubule assembly by approximately 45%. In contrast, the interactive sequences, (131LTITSSLSSDGV(142 and (156ERTIPITRE(164, corresponding to the beta8 strand and the C-terminal extension respectively, which are involved in complex formation, increased microtubule assembly by approximately 34-45%. The alphaB crystallin peptides, (113FISREFHR(120 and (156ERTIPITRE(164, inhibited microtubule disassembly by approximately 26-36%, and the peptides (113FISREFHR(120 and (131LTITSSLSSDGV(142 decreased the thermal aggregation of tubulin by approximately 42-44%. The (131LTITSSLSSDGV(142 and (156ERTIPITRE(164 peptides were more effective than the widely used anti-cancer drug, Paclitaxel, in modulating tubulinmicrotubule dynamics. Mutagenesis of these interactive sequences in wt human alphaB crystallin confirmed the effects of the alphaB crystallin peptides on microtubule assembly/disassembly and tubulin aggregation. The regulation of microtubule assembly by alphaB crystallin varied over a narrow range of concentrations. The assembly of microtubules was maximal at alphaB crystallin to tubulin molar ratios between 1:4 and 2:1, while molar ratios >2:1 inhibited microtubule assembly.Interactive sequences on the surface of human alphaB crystallin collectively modulate microtubule assembly through a dynamic subunit exchange mechanism that depends on the concentration and ratio of alphaB crystallin to tubulin. These are the first

Calcium regulates ATP-sensitive microtubule binding by Chlamydomonas outer arm dynein.

Science.gov (United States)

Sakato, Miho; King, Stephen M

2003-10-31

The Chlamydomonas outer dynein arm contains three distinct heavy chains (alpha, beta, and gamma) that exhibit different motor properties. The LC4 protein, which binds 1-2 Ca2+ with KCa = 3 x 10-5 m, is associated with the gamma heavy chain and has been proposed to act as a sensor to regulate dynein motor function in response to alterations in intraflagellar Ca2+ levels. Here we genetically dissect the outer arm to yield subparticles containing different motor unit combinations and assess the microtubule-binding properties of these complexes both prior to and following preincubation with tubulin and ATP, which was used to inhibit ATP-insensitive (structural) microtubule binding. We observed that the alpha heavy chain exhibits a dominant Ca2+-independent ATP-sensitive MT binding activity in vitro that is inhibited by attachment of tubulin to the structural microtubule-binding domain. Furthermore, we show that ATP-sensitive microtubule binding by a dynein subparticle containing only the beta and gamma heavy chains does not occur at Ca2+ concentrations below pCa 6 but is maximally activated above pCa 5. This activity was not observed in mutant dyneins containing small deletions in the microtubule-binding region of the beta heavy chain or in dyneins that lack both the alpha heavy chain and the motor domain of the beta heavy chain. These findings strongly suggest that Ca2+ binding directly to a component of the dynein complex regulates ATP-sensitive interactions between the beta heavy chain and microtubules and lead to a model for how individual motor units are controlled within the outer dynein arm.

Optical properties of template synthesized nanowalled ZnS microtubules

Science.gov (United States)

Kumar, Rajesh; Chakarvarti, S. K.

2007-12-01

Electrodeposition is a versatile technique combining low processing cost with ambient conditions that can be used to prepare metallic, polymeric and semiconducting nano/micro structures. In the present work, track-etch membranes (TEMs) of makrofol (KG) have been used as templates for synthesis of ZnS nanowalled microtubules using electrodeposition technique. The morphology of the microtubules was characterized by scanning electron microscopy. Size effects on the band gap of tubules have also been studied by UV-visible spectrophotometer.

Regulation of microtubule nucleation mediated by gamma-tubulin complexes

Czech Academy of Sciences Publication Activity Database

Sulimenko, Vadym; Hájková, Zuzana; Klebanovych, Anastasiya; Dráber, Pavel

2017-01-01

Roč. 254, č. 3 (2017), s. 1187-1199 ISSN 0033-183X R&D Projects: GA MŠk(CZ) LD13015 Institutional support: RVO:68378050 Keywords : mitotic spindle formation * ring complex * fission yeast * organizing centers * protein complex * golgi-complex * cell-cycle * pole body * augmin * centrosome * Centrosomes * Microtubule nucleation * Microtubule-organizing centers * Non-centrosomal nucleation sites * Spindle pole bodies * gamma-Tubulin complexes Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Cell biology Impact factor: 2.870, year: 2016

Buckling analysis of orthotropic protein microtubules under axial and radial compression based on couple stress theory.

Science.gov (United States)

Beni, Yaghoub Tadi; Zeverdejani, M Karimi; Mehralian, Fahimeh

2017-10-01

Protein microtubules (MTs) are one of the important intercellular components and have a vital role in the stability and strength of the cells. Due to applied external loads, protein microtubules may be involved buckling phenomenon. Due to impact of protein microtubules in cell reactions, it is important to determine their critical buckling load. Considering nature of protein microtubules, various parameters are effective on microtubules buckling. The small size of microtubules and also lack of uniformity of MTs properties in different directions caused the necessity of accuracy in the analysis of these bio-structure. In fact, microtubules must be considered as a size dependent cylinder, which behave as an orthotropic material. Hence, in the present work using first-order shear deformation model (FSDT), the buckling equations of anisotropic MTs are derived based on new modified couple stress theory (NMCST). After solving the stability equations, the influences of various parameters are measured on the MTs critical buckling load. Copyright © 2017 Elsevier Inc. All rights reserved.

Bundling ecosystem services in Denmark

DEFF Research Database (Denmark)

Turner, Katrine Grace; Odgaard, Mette Vestergaard; Bøcher, Peder Klith

2014-01-01

We made a spatial analysis of 11 ecosystem services at a 10 km × 10 km grid scale covering most of Denmark. Our objective was to describe their spatial distribution and interactions and also to analyze whether they formed specific bundle types on a regional scale in the Danish cultural landscape....... We found clustered distribution patterns of ecosystem services across the country. There was a significant tendency for trade-offs between on the one hand cultural and regulating services and on the other provisioning services, and we also found the potential of regulating and cultural services...... to form synergies. We identified six distinct ecosystem service bundle types, indicating multiple interactions at a landscape level. The bundle types showed specialized areas of agricultural production, high provision of cultural services at the coasts, multifunctional mixed-use bundle types around urban...

Dinitroaniline herbicide resistance and the microtubule cytoskeleton.

Science.gov (United States)

Anthony; Hussey

1999-03-01

Dinitroaniline herbicides have been used for pre-emergence weed control for the past 25 years in cotton, soybean, wheat and oilseed crops. Considering their long persistence and extensive use, resistance to dinitroanilines is fairly rare. However, the most widespread dinitroaniline-resistant weeds, the highly resistant (R) and the intermediate (I) biotypes of the invasive goosegrass Eleusine indica, are now infesting more than 1000 cotton fields in the southern states of the USA. The molecular basis of this resistance has been identified, and found to be a point mutation in a major microtubule cytoskeletal protein, alpha-tubulin. These studies have served both to explain the establishment of resistance and to reveal fundamental properties of tubulin gene expression and microtubule structure.

Tubulin cofactor B regulates microtubule densities during microglia transition to the reactive states

International Nuclear Information System (INIS)

Fanarraga, M.L.; Villegas, J.C.; Carranza, G.; Castano, R.; Zabala, J.C.

2009-01-01

Microglia are highly dynamic cells of the CNS that continuously survey the welfare of the neural parenchyma and play key roles modulating neurogenesis and neuronal cell death. In response to injury or pathogen invasion parenchymal microglia transforms into a more active cell that proliferates, migrates and behaves as a macrophage. The acquisition of these extra skills implicates enormous modifications of the microtubule and actin cytoskeletons. Here we show that tubulin cofactor B (TBCB), which has been found to contribute to various aspects of microtubule dynamics in vivo, is also implicated in microglial cytoskeletal changes. We find that TBCB is upregulated in post-lesion reactive parenchymal microglia/macrophages, in interferon treated BV-2 microglial cells, and in neonate amoeboid microglia where the microtubule densities are remarkably low. Our data demonstrate that upon TBCB downregulation both, after microglia differentiation to the ramified phenotype in vivo and in vitro, or after TBCB gene silencing, microtubule densities are restored in these cells. Taken together these observations support the view that TBCB functions as a microtubule density regulator in microglia during activation, and provide an insight into the understanding of the complex mechanisms controlling microtubule reorganization during microglial transition between the amoeboid, ramified, and reactive phenotypes

Evaluation of droplet deposition in rod bundle

International Nuclear Information System (INIS)

Ji, W.; Gu, C.Y.; Anglart, H.

1997-01-01

Deposition model for droplets in gas droplet two-phase flow in rod bundle is developed in this work using the Lagrangian method. The model is evaluated in a 9-rod bundle geometry. The deposition coefficient in the bundle geometry are compared with that in round tube. The influences of the droplet size and gas mass flow rate on deposition coefficient are investigated. Furthermore, the droplet motion is studied in more detail by dividing the bundle channel into sub-channels. The results show that the overall deposition coefficient in the bundle geometry is close to that in the round tube with the diameter equal to the bundle hydraulic diameter. The calculated deposition coefficient is found to be higher for higher gas mass flux and smaller droplets. The study in the sub-channels show that the ratio between the local deposition coefficient for a sub-channel and the averaged value for the whole bundle is close to a constant value, deviations from the mean value for all the calculated cases being within the range of ±13%. (author)

Dictyoceratidan poisons: Defined mark on microtubule-tubulin dynamics.

Science.gov (United States)

Gnanambal K, Mary Elizabeth; Lakshmipathy, Shailaja Vommi

2016-03-01

Tubulin/microtubule assembly and disassembly is characterized as one of the chief processes during cell growth and division. Hence drugs those perturb these process are considered to be effective in killing fast multiplying cancer cells. There is a collection of natural compounds which disturb microtubule/tubulin dis/assemblage and there have been a lot of efforts concerted in the marine realm too, to surveying such killer molecules. Close to half the natural compounds shooting out from marine invertebrates are generally with no traceable definite mechanisms of action though may be tough anti-cancerous hits at nanogram levels, hence fatefully those discoveries conclude therein without a capacity of translation from laboratory to pharmacy. Astoundingly at least 50% of natural compounds which have definite mechanisms of action causing disorders in tubulin/microtubule kinetics have an isolation history from sponges belonging to the Phylum: Porifera. Poriferans have always been a wonder worker to treat cancers with a choice of, yet precise targets on cancerous tissues. There is a specific order: Dictyoceratida within this Phylum which has contributed to yielding at least 50% of effective compounds possessing this unique mechanism of action mentioned above. However, not much notice is driven to Dictyoceratidans alongside the order: Demospongiae thus dictating the need to know its select microtubule/tubulin irritants since the unearthing of avarol in the year 1974 till date. Hence this review selectively pinpoints all the compounds, noteworthy derivatives and analogs stemming from order: Dictyoceratida focusing on the past, present and future. Copyright © 2016 Elsevier Inc. All rights reserved.

Bundle Security Protocol for ION

Science.gov (United States)

Burleigh, Scott C.; Birrane, Edward J.; Krupiarz, Christopher

2011-01-01

This software implements bundle authentication, conforming to the Delay-Tolerant Networking (DTN) Internet Draft on Bundle Security Protocol (BSP), for the Interplanetary Overlay Network (ION) implementation of DTN. This is the only implementation of BSP that is integrated with ION.

Connections on discrete fibre bundles

International Nuclear Information System (INIS)

Manton, N.S.; Cambridge Univ.

1987-01-01

A new approach to gauge fields on a discrete space-time is proposed, in which the fundamental object is a discrete version of a principal fibre bundle. If the bundle is twisted, the gauge fields are topologically non-trivial automatically. (orig.)

Msd1/SSX2IP-dependent microtubule anchorage ensures spindle orientation and primary cilia formation

OpenAIRE

Hori, Akiko; Ikebe, Chiho; Tada, Masazumi; Toda, Takashi

2014-01-01

Anchoring microtubules to the centrosome is critical for cell geometry and polarity, yet the molecular mechanism remains unknown. Here we show that the conserved human Msd1/SSX2IP is required for microtubule anchoring. hMsd1/SSX2IP is delivered to the centrosome in a centriolar satellite-dependent manner and binds the microtubule-nucleator ?-tubulin complex. hMsd1/SSX2IP depletion leads to disorganised interphase microtubules and misoriented mitotic spindles with reduced length and intensity....

Deformation quantization of principal fibre bundles

International Nuclear Information System (INIS)

Weiss, S.

2007-01-01

Deformation quantization is an algebraic but still geometrical way to define noncommutative spacetimes. In order to investigate corresponding gauge theories on such spaces, the geometrical formulation in terms of principal fibre bundles yields the appropriate framework. In this talk I will explain what should be understood by a deformation quantization of principal fibre bundles and how associated vector bundles arise in this context. (author)

Deformations of the generalised Picard bundle

International Nuclear Information System (INIS)

Biswas, I.; Brambila-Paz, L.; Newstead, P.E.

2004-08-01

Let X be a nonsingular algebraic curve of genus g ≥ 3, and let Mξ denote the moduli space of stable vector bundles of rank n ≥ 2 and degree d with fixed determinant ξ over X such that n and d are coprime. We assume that if g = 3 then n ≥ 4 and if g = 4 then n ≥ 3, and suppose further that n 0 , d 0 are integers such that n 0 ≥ 1 and nd 0 + n 0 d > nn 0 (2g - 2). Let E be a semistable vector bundle over X of rank n 0 and degree d 0 . The generalised Picard bundle W ξ (E) is by definition the vector bundle over M ξ defined by the direct image p M ξ *(U ξ x p X * E) where U ξ is a universal vector bundle over X x M ξ . We obtain an inversion formula allowing us to recover E from W ξ (E) and show that the space of infinitesimal deformations of W ξ (E) is isomorphic to H 1 (X, End(E)). This construction gives a locally complete family of vector bundles over M ξ parametrised by the moduli space M(n 0 ,d 0 ) of stable bundles of rank n 0 and degree d 0 over X. If (n 0 ,d 0 ) = 1 and W ξ (E) is stable for all E is an element of M(n 0 ,d 0 ), the construction determines an isomorphism from M(n 0 ,d 0 ) to a connected component M 0 of a moduli space of stable sheaves over M ξ . This applies in particular when n 0 = 1, in which case M 0 is isomorphic to the Jacobian J of X as a polarised variety. The paper as a whole is a generalisation of results of Kempf and Mukai on Picard bundles over J, and is also related to a paper of Tyurin on the geometry of moduli of vector bundles. (author)

ATPase Cycle of the Nonmotile Kinesin NOD Allows Microtubule End Tracking and Drives Chromosome Movement

Energy Technology Data Exchange (ETDEWEB)

Cochran, J.; Sindelar, C; Mulko, N; Collins, K; Kong, S; Hawley, R; Kull, F

2009-01-01

Segregation of nonexchange chromosomes during Drosophila melanogaster meiosis requires the proper function of NOD, a nonmotile kinesin-10. We have determined the X-ray crystal structure of the NOD catalytic domain in the ADP- and AMPPNP-bound states. These structures reveal an alternate conformation of the microtubule binding region as well as a nucleotide-sensitive relay of hydrogen bonds at the active site. Additionally, a cryo-electron microscopy reconstruction of the nucleotide-free microtubule-NOD complex shows an atypical binding orientation. Thermodynamic studies show that NOD binds tightly to microtubules in the nucleotide-free state, yet other nucleotide states, including AMPPNP, are weakened. Our pre-steady-state kinetic analysis demonstrates that NOD interaction with microtubules occurs slowly with weak activation of ADP product release. Upon rapid substrate binding, NOD detaches from the microtubule prior to the rate-limiting step of ATP hydrolysis, which is also atypical for a kinesin. We propose a model for NOD's microtubule plus-end tracking that drives chromosome movement.

The dynamic interplay of plasma membrane domains and cortical microtubules in secondary cell wall patterning

Directory of Open Access Journals (Sweden)

Yoshihisa eOda

2013-12-01

Full Text Available Patterning of the cellulosic cell wall underlies the shape and function of plant cells. The cortical microtubule array plays a central role in the regulation of cell wall patterns. However, the regulatory mechanisms by which secondary cell wall patterns are established through cortical microtubules remain to be fully determined. Our recent study in xylem vessel cells revealed that a mutual inhibitory interaction between cortical microtubules and distinct plasma membrane domains leads to distinctive patterning in secondary cell walls. Our research revealed that the recycling of active and inactive ROP proteins by a specific GAP and GEF pair establishes distinct de novo plasma membrane domains. Active ROP recruits a plant-specific microtubule-associated protein, MIDD1, which mediates the mutual interaction between cortical microtubules and plasma membrane domains. In this mini review, we summarize recent research regarding secondary wall patterning, with a focus on the emerging interplay between plasma membrane domains and cortical microtubules through MIDD1 and ROP.

The engine of microtubule dynamics comes into focus.

Science.gov (United States)

Mitchison, T J

2014-05-22

In this issue, Alushin et al. report high-resolution structures of three states of the microtubule lattice: GTP-bound, which is stable to depolymerization; unstable GDP-bound; and stable Taxol and GDP-bound. By comparing these structures at near-atomic resolution, they are able to propose a detailed model for how GTP hydrolysis destabilizes the microtubule and thus powers dynamic instability and chromosome movement. Destabilization of cytoskeleton filaments by nucleotide hydrolysis is an important general principle in cell dynamics, and this work represents a major step forward on a problem with a long history. Copyright © 2014 Elsevier Inc. All rights reserved.

Functional Importance of the Anaphase-Promoting Complex-Cdh1-Mediated Degradation of TMAP/CKAP2 in Regulation of Spindle Function and Cytokinesis▿ †

OpenAIRE

Hong, Kyung Uk; Park, Young Soo; Seong, Yeon-Sun; Kang, Dongmin; Bae, Chang-Dae; Park, Joobae

2007-01-01

Cytoskeleton-associated protein 2 (CKAP2), also known as tumor-associated microtubule-associated protein (TMAP), is a novel microtubule-associated protein that is frequently upregulated in various malignances. However, its cellular functions remain unknown. A previous study has shown that its protein level begins to increase during G1/S and peaks at G2/M, after which it decreases abruptly. Ectopic overexpression of TMAP/CKAP2 induced microtubule bundling related to increased microtubule stabi...

Stability of Picard bundle over moduli space of stable vector bundles ...

Indian Academy of Sciences (India)

Springer Verlag Heidelberg #4 2048 1996 Dec 15 10:16:45

Since the morphism ϕ is given by the universal property of the moduli space, the pullback of the universal bundle E on X × M to X × P by the map idX × ϕ is isomorphic (up to a twist by a line bundle coming from P) to ˜E. In other words, there is an integer k such that. 0 −→ (idX × ϕ)∗E −→ W ⊠ OP (k) −→ Ox×P (k + 1) −→ 0.

Characteristics of CANDU fuel bundles that caused pressure tube fretting at the bundle midplane

Energy Technology Data Exchange (ETDEWEB)

Dennier, D; Manzer, A M [Atomic Energy of Canada Ltd., Mississauga, ON (Canada); Koehn, E [Ontario Hydro, Toronto, ON (Canada)

1996-12-31

Detailed measurements on new bundles, and those that caused fretting during in- and out-reactor tests, have given insight into the factors responsible for fretting at the midplane of the inlet bundle. Bottom fuel elements that were attached near radial endplate spokes and had inboard bearing pads in the rolled joint cavity produced a significant portion of the observed fret marks. These elements are influenced by several driving forces that deflect the centre bearing pads towards the pressure tube surface. The evidence suggests that slight changes in bundle design may be possible to reduce pressure tube fretting. (author). 4 refs., 3 tabs., 8 figs.

Study of fuel bundle geometry on inter subchannel flow in a 19 pin wire wrapped bundle

International Nuclear Information System (INIS)

Naveen Raj, M.; Velusamy, D.K.

2015-01-01

In typical sodium cooled fast reactor (SFR) fuel pin bundle, gap between the pins is maintained by helically wound wire wrap around each pin. The presence of wire induces large inter-subchannel transverse flow, eventually promoting mixing and heat transfer. The magnitude of the transverse flow is highly dependent on the various pin-bundle dimensions. Appropriate modeling of these transverse flows in subchannel codes is necessary to predict realistic temperature distribution in pin bundle. Hence, detailed parametric study of transverse flow on pin-bundle geometric parameters has been conducted. The parameters taken for the present study are pin diameter, wire diameter, helical wire pitch and edge gap. Towards this 3-D computational fluid dynamic analysis on a structured mesh of 19 pin bundle is carried out using k-epsilon turbulence model. Periodic oscillations along the primacy flow direction were found in subchannel transverse flow and peripheral pin clad temperatures with periodicity over one pitch length. Based on parametric studies, correlations for transverse flow in central subchannels are proposed. (author)

Microtubules Nonlinear Models Dynamics Investigations through the exp(−Φ(ξ-Expansion Method Implementation

Directory of Open Access Journals (Sweden)

Nur Alam

2016-02-01

Full Text Available In this research article, we present exact solutions with parameters for two nonlinear model partial differential equations(PDEs describing microtubules, by implementing the exp(−Φ(ξ-Expansion Method. The considered models, describing highly nonlinear dynamics of microtubules, can be reduced to nonlinear ordinary differential equations. While the first PDE describes the longitudinal model of nonlinear dynamics of microtubules, the second one describes the nonlinear model of dynamics of radial dislocations in microtubules. The acquired solutions are then graphically presented, and their distinct properties are enumerated in respect to the corresponding dynamic behavior of the microtubules they model. Various patterns, including but not limited to regular, singular kink-like, as well as periodicity exhibiting ones, are detected. Being the method of choice herein, the exp(−Φ(ξ-Expansion Method not disappointing in the least, is found and declared highly efficient.

Centriole triplet microtubules are required for stable centriole formation and inheritance in human cells.

Science.gov (United States)

Wang, Jennifer T; Kong, Dong; Hoerner, Christian R; Loncarek, Jadranka; Stearns, Tim

2017-09-14

Centrioles are composed of long-lived microtubules arranged in nine triplets. However, the contribution of triplet microtubules to mammalian centriole formation and stability is unknown. Little is known of the mechanism of triplet microtubule formation, but experiments in unicellular eukaryotes indicate that delta-tubulin and epsilon-tubulin, two less-studied tubulin family members, are required. Here, we report that centrioles in delta-tubulin and epsilon-tubulin null mutant human cells lack triplet microtubules and fail to undergo centriole maturation. These aberrant centrioles are formed de novo each cell cycle, but are unstable and do not persist to the next cell cycle, leading to a futile cycle of centriole formation and disintegration. Disintegration can be suppressed by paclitaxel treatment. Delta-tubulin and epsilon-tubulin physically interact, indicating that these tubulins act together to maintain triplet microtubules and that these are necessary for inheritance of centrioles from one cell cycle to the next.

Stabilization, not polymerization, of microtubules inhibits the nuclear translocation of STATs in adipocytes

International Nuclear Information System (INIS)

Gleason, Evanna L.; Hogan, Jessica C.; Stephens, Jacqueline M.

2004-01-01

Signal transducers and activators of transcriptions (STATs) are a family of latent transcription factors which are activated by a variety of growth factors and cytokines in many cell types. However, the mechanism by which these transcription factors translocate to the nucleus is poorly understood. The goal of this study was to determine the requirement of microfilaments and microtubules for cytokine induced STAT activation in cultured adipocytes. We used seven different actin-specific and microtubule-specific agents that are well-established effectors of these cytoskeletal networks. Our results clearly demonstrate that inhibition of microfilaments or the prevention of microtubule polymerization has no effect on the ability of STATs to be tyrosine phosphorylated or to translocate to the nucleus. However, we observed that paclitaxel, a microtubule stabilizer, resulted in a significant decrease in the nuclear translocation of STATs without affecting the cytosolic tyrosine phosphorylation of these transcription factors. In summary, our results demonstrate that the dynamic instability, but not the polymerization, of microtubules contributes to nuclear translocation of STAT proteins in adipocytes

Disruption of microtubule network rescues aberrant actin comets in dynamin2-depleted cells.

Directory of Open Access Journals (Sweden)

Yuji Henmi

Full Text Available A large GTPase dynamin, which is required for endocytic vesicle formation, regulates the actin cytoskeleton through its interaction with cortactin. Dynamin2 mutants impair the formation of actin comets, which are induced by Listeria monocytogenes or phosphatidylinositol-4-phosphate 5-kinase. However, the role of dynamin2 in the regulation of the actin comet is still unclear. Here we show that aberrant actin comets in dynamin2-depleted cells were rescued by disrupting of microtubule networks. Depletion of dynamin2, but not cortactin, significantly reduced the length and the speed of actin comets induced by Listeria. This implies that dynamin2 may regulate the actin comet in a cortactin-independent manner. As dynamin regulates microtubules, we investigated whether perturbation of microtubules would rescue actin comet formation in dynamin2-depleted cells. Treatment with taxol or colchicine created a microtubule-free space in the cytoplasm, and made no difference between control and dynamin2 siRNA cells. This suggests that the alteration of microtubules by dynamin2 depletion reduced the length and the speed of the actin comet.

Modeling microtubule oscillations

DEFF Research Database (Denmark)

Jobs, E.; Wolf, D.E.; Flyvbjerg, H.

1997-01-01

Synchronization of molecular reactions in a macroscopic volume may cause the volume's physical properties to change dynamically and thus reveal much about the reactions. As an example, experimental time series for so-called microtubule oscillations are analyzed in terms of a minimal model...... for this complex polymerization-depolymerization cycle. The model reproduces well the qualitatively different time series that result from different experimental conditions, and illuminates the role and importance of individual processes in the cycle. Simple experiments are suggested that can further test...... and define the model and the polymer's reaction cycle....

A ROP2-RIC1 pathway fine-tunes microtubule reorganization for salt tolerance in Arabidopsis.

Science.gov (United States)

Li, Changjiang; Lu, Hanmei; Li, Wei; Yuan, Ming; Fu, Ying

2017-07-01

The reorganization of microtubules induced by salt stress is required for Arabidopsis survival under high salinity conditions. RIC1 is an effector of Rho-related GTPase from plants (ROPs) and a known microtubule-associated protein. In this study, we demonstrated that RIC1 expression decreased with long-term NaCl treatment, and ric1-1 seedlings exhibited a higher survival rate under salt stress. We found that RIC1 reduced the frequency of microtubule transition from shortening to growing status and knockout of RIC1 improved the reassembly of depolymerized microtubules caused by either oryzalin treatment or salt stress. Further investigation showed that constitutively active ROP2 promoted the reassembly of microtubules and the survival of seedlings under salt stress. A rop2-1 ric1-1 double mutant rescued the salt-sensitive phenotype of rop2-1, indicating that ROP2 functions in salt tolerance through RIC1. Although ROP2 did not regulate RIC1 expression upon salt stress, a quick but mild increase of ROP2 activity was induced, led to reduction of RIC1 on microtubules. Collectively, our study reveals an ROP2-RIC1 pathway that fine-tunes microtubule dynamics in response to salt stress in Arabidopsis. This finding not only reveals a new regulatory mechanism for microtubule reorganization under salt stress but also the importance of ROP signalling for salinity tolerance. © 2017 John Wiley & Sons Ltd.

Luminal localization of α-tubulin K40 acetylation by cryo-EM analysis of fab-labeled microtubules.

Directory of Open Access Journals (Sweden)

Virupakshi Soppina

Full Text Available The αβ-tubulin subunits of microtubules can undergo a variety of evolutionarily-conserved post-translational modifications (PTMs that provide functional specialization to subsets of cellular microtubules. Acetylation of α-tubulin residue Lysine-40 (K40 has been correlated with increased microtubule stability, intracellular transport, and ciliary assembly, yet a mechanistic understanding of how acetylation influences these events is lacking. Using the anti-acetylated tubulin antibody 6-11B-1 and electron cryo-microscopy, we demonstrate that the K40 acetylation site is located inside the microtubule lumen and thus cannot directly influence events on the microtubule surface, including kinesin-1 binding. Surprisingly, the monoclonal 6-11B-1 antibody recognizes both acetylated and deacetylated microtubules. These results suggest that acetylation induces structural changes in the K40-containing loop that could have important functional consequences on microtubule stability, bending, and subunit interactions. This work has important implications for acetylation and deacetylation reaction mechanisms as well as for interpreting experiments based on 6-11B-1 labeling.

Hydraulic characteristics of HANARO fuel bundles

Energy Technology Data Exchange (ETDEWEB)

Cho, S; Chung, H J; Chun, S Y; Yang, S K; Chung, M K [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

1998-12-31

This paper presents the hydraulic characteristics measured by using LDV (Laser Doppler Velocimetry) in subchannels of HANARO, KAERI research reactor, fuel bundle. The fuel bundle consists of 18 axially finned rods with 3 spacer grids, which are arranged in cylindrical configuration. The effects of the spacer grids on the turbulent flow were investigated by the experimental results. Pressure drops for each component of the fuel bundle were measured, and the friction factors of fuel bundle and loss coefficients for the spacer grids were estimated from the measured pressure drops. Implications regarding the turbulent thermal mixing were discussed. Vibration test results measured by using laser vibrometer were presented. 9 refs., 12 figs. (Author)

Hydraulic characteristics of HANARO fuel bundles

Energy Technology Data Exchange (ETDEWEB)

Cho, S.; Chung, H. J.; Chun, S. Y.; Yang, S. K.; Chung, M. K. [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

1997-12-31

This paper presents the hydraulic characteristics measured by using LDV (Laser Doppler Velocimetry) in subchannels of HANARO, KAERI research reactor, fuel bundle. The fuel bundle consists of 18 axially finned rods with 3 spacer grids, which are arranged in cylindrical configuration. The effects of the spacer grids on the turbulent flow were investigated by the experimental results. Pressure drops for each component of the fuel bundle were measured, and the friction factors of fuel bundle and loss coefficients for the spacer grids were estimated from the measured pressure drops. Implications regarding the turbulent thermal mixing were discussed. Vibration test results measured by using laser vibrometer were presented. 9 refs., 12 figs. (Author)

In-pool damaged fuel bundle recovery

International Nuclear Information System (INIS)

Piascik, T.G.; Patenaude, R.S.

1988-01-01

While preparing to rerack the Oyster Creek Nuclear Generating Station, GPU Nuclear had need to move a damaged fuel bundle. This bundle had no upper tie plate and could not be moved in the normal manner. GPU Nuclear formed a small, dedicated project team to disassemble, package and move this damaged bundle. The team was composed of key personnel from GPU Nuclear Fuels Projects, OCNGS Operations and Proto-Power / Bisco, a specialty contractor who has fuel bundle reconstitution and rod consolidation experience, remote tooling, underwater video systems and experienced technicians. Proven tooling, clear procedures and a simple approach were important, but the key element was the spirit of teamwork and leadership exhibited by the people involved

Verification of the FBR fuel bundle-duct interaction analysis code BAMBOO by the out-of-pile bundle compression test with large diameter pins

Science.gov (United States)

Uwaba, Tomoyuki; Ito, Masahiro; Nemoto, Junichi; Ichikawa, Shoichi; Katsuyama, Kozo

2014-09-01

The BAMBOO computer code was verified by results for the out-of-pile bundle compression test with large diameter pin bundle deformation under the bundle-duct interaction (BDI) condition. The pin diameters of the examined test bundles were 8.5 mm and 10.4 mm, which are targeted as preliminary fuel pin diameters for the upgraded core of the prototype fast breeder reactor (FBR) and for demonstration and commercial FBRs studied in the FaCT project. In the bundle compression test, bundle cross-sectional views were obtained from X-ray computer tomography (CT) images and local parameters of bundle deformation such as pin-to-duct and pin-to-pin clearances were measured by CT image analyses. In the verification, calculation results of bundle deformation obtained by the BAMBOO code analyses were compared with the experimental results from the CT image analyses. The comparison showed that the BAMBOO code reasonably predicts deformation of large diameter pin bundles under the BDI condition by assuming that pin bowing and cladding oval distortion are the major deformation mechanisms, the same as in the case of small diameter pin bundles. In addition, the BAMBOO analysis results confirmed that cladding oval distortion effectively suppresses BDI in large diameter pin bundles as well as in small diameter pin bundles.

Shaping the tracks : Regulation of microtubule dynamics by kinesins KIF21A and KIF21B

NARCIS (Netherlands)

van Riel, W.E.|info:eu-repo/dai/nl/338772634

2016-01-01

Control of microtubule dynamics is important for cell morphogenesis. Kinesins, motor proteins known to function in cargo transport, were recently also implicated in altering the microtubule network. Several kinesins are described to cause microtubule network reorganization or stabilization, either

Moonlighting microtubule-associated proteins: regulatory functions by day and pathological functions at night.

Science.gov (United States)

Oláh, J; Tőkési, N; Lehotzky, A; Orosz, F; Ovádi, J

2013-11-01

The sensing, integrating, and coordinating features of the eukaryotic cells are achieved by the complex ultrastructural arrays and multifarious functions of the cytoskeletal network. Cytoskeleton comprises fibrous protein networks of microtubules, actin, and intermediate filaments. These filamentous polymer structures are highly dynamic and undergo constant and rapid reorganization during cellular processes. The microtubular system plays a crucial role in the brain, as it is involved in an enormous number of cellular events including cell differentiation and pathological inclusion formation. These multifarious functions of microtubules can be achieved by their decoration with proteins/enzymes that exert specific effects on the dynamics and organization of the cytoskeleton and mediate distinct functions due to their moonlighting features. This mini-review focuses on two aspects of the microtubule cytoskeleton. On the one hand, we describe the heteroassociation of tubulin/microtubules with metabolic enzymes, which in addition to their catalytic activities stabilize microtubule structures via their cross-linking functions. On the other hand, we focus on the recently identified moonlighting tubulin polymerization promoting protein, TPPP/p25. TPPP/p25 is a microtubule-associated protein and it displays distinct physiological or pathological (aberrant) functions; thus it is a prototype of Neomorphic Moonlighting Proteins. The expression of TPPP/p25 is finely controlled in the human brain; this protein is indispensable for the development of projections of oligodendrocytes that are responsible for the ensheathment of axons. The nonphysiological, higher or lower TPPP/p25 level leads to distinct CNS diseases. Mechanisms contributing to the control of microtubule stability and dynamics by metabolic enzymes and TPPP/p25 will be discussed. Copyright © 2013 Wiley Periodicals, Inc.

Cep192 controls the balance of centrosome and non-centrosomal microtubules during interphase.

Directory of Open Access Journals (Sweden)

Brian P O'Rourke

Full Text Available Cep192 is a centrosomal protein that contributes to the formation and function of the mitotic spindle in mammalian cells. Cep192's mitotic activities stem largely from its role in the recruitment to the centrosome of numerous additional proteins such as gamma-tubulin and Pericentrin. Here, we examine Cep192's function in interphase cells. Our data indicate that, as in mitosis, Cep192 stimulates the nucleation of centrosomal microtubules thereby regulating the morphology of interphase microtubule arrays. Interestingly, however, cells lacking Cep192 remain capable of generating normal levels of MTs as the loss of centrosomal microtubules is augmented by MT nucleation from other sites, most notably the Golgi apparatus. The depletion of Cep192 results in a significant decrease in the level of centrosome-associated gamma-tubulin, likely explaining its impact on centrosome microtubule nucleation. However, in stark contrast to mitosis, Cep192 appears to maintain an antagonistic relationship with Pericentrin at interphase centrosomes. Interphase cells depleted of Cep192 display significantly higher levels of centrosome-associated Pericentrin while overexpression of Cep192 reduces the levels of centrosomal Pericentrin. Conversely, depletion of Pericentrin results in elevated levels of centrosomal Cep192 and enhances microtubule nucleation at centrosomes, at least during interphase. Finally, we show that depletion of Cep192 negatively impacts cell motility and alters normal cell polarization. Our current working hypothesis is that the microtubule nucleating capacity of the interphase centrosome is determined by an antagonistic balance of Cep192, which promotes nucleation, and Pericentrin, which inhibits nucleation. This in turn determines the relative abundance of centrosomal and non-centrosomal microtubules that tune cell movement and shape.

Anatomic Double-bundle ACL Reconstruction

NARCIS (Netherlands)

Schreiber, Verena M.; van Eck, Carola F.; Fu, Freddie H.

2010-01-01

Rupture of the anterior cruciate ligament (ACL) is one of the most frequent forms of knee trauma. The traditional surgical treatment for ACL rupture is single-bundle reconstruction. However, during the past few years there has been a shift in interest toward double-bundle reconstruction to closely

Output commitment through product bundling : Experimental evidence

NARCIS (Netherlands)

Hinloopen, Jeroen; Mueller, Wieland; Normann, Hans-Theo

We analyze the impact of product bundling in experimental markets. One firm has monopoly power in a first market but competes with another firm la Cournot in a second market. We compare treatments where the multi-product firm (i) always bundles, (ii) never bundles, and (iii) chooses whether to

Differential regulation of microtubule severing by APC underlies distinct patterns of projection neuron and interneuron migration

Science.gov (United States)

Eom, Tae-Yeon; Stanco, Amelia; Guo, Jiami; Wilkins, Gary; Deslauriers, Danielle; Yan, Jessica; Monckton, Chase; Blair, Josh; Oon, Eesim; Perez, Abby; Salas, Eduardo; Oh, Adrianna; Ghukasyan, Vladimir; Snider, William D.; Rubenstein, John L. R.; Anton, E. S.

2014-01-01

Coordinated migration of distinct classes of neurons to appropriate positions leads to the formation of functional neuronal circuitry in the cerebral cortex. Two major classes of cortical neurons, interneurons and projection neurons, utilize distinctly different modes (radial vs. tangential) and routes of migration to arrive at their final positions in the cerebral cortex. Here, we show that adenomatous polyposis coli (APC) modulates microtubule (MT) severing in interneurons to facilitate tangential mode of interneuron migration, but not the glial-guided, radial migration of projection neurons. APC regulates the stability and activity of the MT severing protein p60-katanin in interneurons to promote the rapid remodeling of neuronal processes necessary for interneuron migration. These findings reveal how severing and restructuring of MTs facilitate distinct modes of neuronal migration necessary for laminar organization of neurons in the developing cerebral cortex. PMID:25535916

ACM Bundles on Del Pezzo surfaces

Directory of Open Access Journals (Sweden)

Joan Pons-Llopis

2009-11-01

Full Text Available ACM rank 1 bundles on del Pezzo surfaces are classified in terms of the rational normal curves that they contain. A complete list of ACM line bundles is provided. Moreover, for any del Pezzo surface X of degree less or equal than six and for any n ≥ 2 we construct a family of dimension ≥ n − 1 of non-isomorphic simple ACM bundles of rank n on X.

Bundling and mergers in energy markets

International Nuclear Information System (INIS)

Granier, Laurent; Podesta, Marion

2010-01-01

Does bundling trigger mergers in energy industries? We observe mergers between firms belonging to various energy markets, for instance between gas and electricity providers. These mergers enable firms to bundle. We consider two horizontally differentiated markets. In this framework, we show that bundling strategies in energy markets create incentives to form multi-market firms in order to supply bi-energy packages. Moreover, we find that this type of merger is detrimental to social welfare. (author)

Computational imaging through a fiber-optic bundle

Science.gov (United States)

Lodhi, Muhammad A.; Dumas, John Paul; Pierce, Mark C.; Bajwa, Waheed U.

2017-05-01

Compressive sensing (CS) has proven to be a viable method for reconstructing high-resolution signals using low-resolution measurements. Integrating CS principles into an optical system allows for higher-resolution imaging using lower-resolution sensor arrays. In contrast to prior works on CS-based imaging, our focus in this paper is on imaging through fiber-optic bundles, in which manufacturing constraints limit individual fiber spacing to around 2 μm. This limitation essentially renders fiber-optic bundles as low-resolution sensors with relatively few resolvable points per unit area. These fiber bundles are often used in minimally invasive medical instruments for viewing tissue at macro and microscopic levels. While the compact nature and flexibility of fiber bundles allow for excellent tissue access in-vivo, imaging through fiber bundles does not provide the fine details of tissue features that is demanded in some medical situations. Our hypothesis is that adapting existing CS principles to fiber bundle-based optical systems will overcome the resolution limitation inherent in fiber-bundle imaging. In a previous paper we examined the practical challenges involved in implementing a highly parallel version of the single-pixel camera while focusing on synthetic objects. This paper extends the same architecture for fiber-bundle imaging under incoherent illumination and addresses some practical issues associated with imaging physical objects. Additionally, we model the optical non-idealities in the system to get lower modelling errors.

Centriole triplet microtubules are required for stable centriole formation and inheritance in human cells

Science.gov (United States)

Wang, Jennifer T; Kong, Dong; Hoerner, Christian R; Loncarek, Jadranka

2017-01-01

Centrioles are composed of long-lived microtubules arranged in nine triplets. However, the contribution of triplet microtubules to mammalian centriole formation and stability is unknown. Little is known of the mechanism of triplet microtubule formation, but experiments in unicellular eukaryotes indicate that delta-tubulin and epsilon-tubulin, two less-studied tubulin family members, are required. Here, we report that centrioles in delta-tubulin and epsilon-tubulin null mutant human cells lack triplet microtubules and fail to undergo centriole maturation. These aberrant centrioles are formed de novo each cell cycle, but are unstable and do not persist to the next cell cycle, leading to a futile cycle of centriole formation and disintegration. Disintegration can be suppressed by paclitaxel treatment. Delta-tubulin and epsilon-tubulin physically interact, indicating that these tubulins act together to maintain triplet microtubules and that these are necessary for inheritance of centrioles from one cell cycle to the next. PMID:28906251

Standard-model bundles

CERN Document Server

Donagi, Ron; Pantev, Tony; Waldram, Dan; Donagi, Ron; Ovrut, Burt; Pantev, Tony; Waldram, Dan

2002-01-01

We describe a family of genus one fibered Calabi-Yau threefolds with fundamental group ${\\mathbb Z}/2$. On each Calabi-Yau $Z$ in the family we exhibit a positive dimensional family of Mumford stable bundles whose symmetry group is the Standard Model group $SU(3)\\times SU(2)\\times U(1)$ and which have $c_{3} = 6$. We also show that for each bundle $V$ in our family, $c_{2}(Z) - c_{2}(V)$ is the class of an effective curve on $Z$. These conditions ensure that $Z$ and $V$ can be used for a phenomenologically relevant compactification of Heterotic M-theory.

An in vitro biomechanical comparison of anterior cruciate ligament reconstruction: single bundle versus anatomical double bundle techniques

Directory of Open Access Journals (Sweden)

Sandra Umeda Sasaki

2008-01-01

Full Text Available INTRODUCTION: Anterior cruciate ligament ruptures are frequent, especially in sports. Surgical reconstruction with autologous grafts is widely employed in the international literature. Controversies remain with respect to technique variations as continuous research for improvement takes place. One of these variations is the anatomical double bundle technique, which is performed instead of the conventional single bundle technique. More recently, there has been a tendency towards positioning the two bundles through double bone tunnels in the femur and tibia (anatomical reconstruction. OBJECTIVES: To compare, through biomechanical tests, the practice of anatomical double bundle anterior cruciate ligament reconstruction with a patellar graft to conventional single bundle reconstruction with the same amount of patellar graft in a paired experimental cadaver study. METHODS: Nine pairs of male cadaver knees ranging in age from 44 to 63 years were randomized into two groups: group A (single bundle and group B (anatomical reconstruction. Each knee was biomechanically tested under three conditions: intact anterior cruciate ligament, reconstructed anterior cruciate ligament, and injured anterior cruciate ligament. Maximum anterior dislocation, rigidity, and passive internal tibia rotation were recorded with knees submitted to a 100 N horizontal anterior dislocation force applied to the tibia with the knees at 30, 60 and 90 degrees of flexion. RESULTS: There were no differences between the two techniques for any of the measurements by ANOVA tests. CONCLUSION: The technique of anatomical double bundle reconstruction of the anterior cruciate ligament with bone-patellar tendon-bone graft has a similar biomechanical behavior with regard to anterior tibial dislocation, rigidity, and passive internal tibial rotation.

Taking directions: the role of microtubule-bound nucleation in the self-organization of the plant cortical array

International Nuclear Information System (INIS)

Deinum, Eva E; Tindemans, Simon H; Mulder, Bela M

2011-01-01

The highly aligned cortical microtubule array of interphase plant cells is a key regulator of anisotropic cell expansion. Recent computational and analytical work has shown that the non-equilibrium self-organization of this structure can be understood on the basis of experimentally observed collisional interactions between dynamic microtubules attached to the plasma membrane. Most of these approaches assumed that new microtubules are homogeneously and isotropically nucleated on the cortical surface. Experimental evidence, however, shows that nucleation mostly occurs from other microtubules and under specific relative angles. Here, we investigate the impact of directed microtubule-bound nucleations on the alignment process using computer simulations. The results show that microtubule-bound nucleations can increase the degree of alignment achieved, decrease the timescale of the ordering process and widen the regime of dynamic parameters for which the system can self-organize. We establish that the major determinant of this effect is the degree of co-alignment of the nucleations with the parent microtubule. The specific role of sideways branching nucleations appears to allow stronger alignment while maintaining a measure of overall spatial homogeneity. Finally, we investigate the suggestion that observed persistent rotation of microtubule domains can be explained through a handedness bias in microtubule-bound nucleations, showing that this is possible only for an extreme bias and over a limited range of parameters

Taking directions: the role of microtubule-bound nucleation in the self-organization of the plant cortical array

Science.gov (United States)

Deinum, Eva E.; Tindemans, Simon H.; Mulder, Bela M.

2011-10-01

The highly aligned cortical microtubule array of interphase plant cells is a key regulator of anisotropic cell expansion. Recent computational and analytical work has shown that the non-equilibrium self-organization of this structure can be understood on the basis of experimentally observed collisional interactions between dynamic microtubules attached to the plasma membrane. Most of these approaches assumed that new microtubules are homogeneously and isotropically nucleated on the cortical surface. Experimental evidence, however, shows that nucleation mostly occurs from other microtubules and under specific relative angles. Here, we investigate the impact of directed microtubule-bound nucleations on the alignment process using computer simulations. The results show that microtubule-bound nucleations can increase the degree of alignment achieved, decrease the timescale of the ordering process and widen the regime of dynamic parameters for which the system can self-organize. We establish that the major determinant of this effect is the degree of co-alignment of the nucleations with the parent microtubule. The specific role of sideways branching nucleations appears to allow stronger alignment while maintaining a measure of overall spatial homogeneity. Finally, we investigate the suggestion that observed persistent rotation of microtubule domains can be explained through a handedness bias in microtubule-bound nucleations, showing that this is possible only for an extreme bias and over a limited range of parameters.

Reduction of symplectic principal R-bundles

International Nuclear Information System (INIS)

Lacirasella, Ignazio; Marrero, Juan Carlos; Padrón, Edith

2012-01-01

We describe a reduction process for symplectic principal R-bundles in the presence of a momentum map. These types of structures play an important role in the geometric formulation of non-autonomous Hamiltonian systems. We apply this procedure to the standard symplectic principal R-bundle associated with a fibration π:M→R. Moreover, we show a reduction process for non-autonomous Hamiltonian systems on symplectic principal R-bundles. We apply these reduction processes to several examples. (paper)

Bundles of C*-categories and duality

OpenAIRE

Vasselli, Ezio

2005-01-01

We introduce the notions of multiplier C*-category and continuous bundle of C*-categories, as the categorical analogues of the corresponding C*-algebraic notions. Every symmetric tensor C*-category with conjugates is a continuous bundle of C*-categories, with base space the spectrum of the C*-algebra associated with the identity object. We classify tensor C*-categories with fibre the dual of a compact Lie group in terms of suitable principal bundles. This also provides a classification for ce...

GDP-to-GTP exchange on the microtubule end can contribute to the frequency of catastrophe.

Science.gov (United States)

Piedra, Felipe-Andrés; Kim, Tae; Garza, Emily S; Geyer, Elisabeth A; Burns, Alexander; Ye, Xuecheng; Rice, Luke M

2016-11-07

Microtubules are dynamic polymers of αβ-tubulin that have essential roles in chromosome segregation and organization of the cytoplasm. Catastrophe-the switch from growing to shrinking-occurs when a microtubule loses its stabilizing GTP cap. Recent evidence indicates that the nucleotide on the microtubule end controls how tightly an incoming subunit will be bound (trans-acting GTP), but most current models do not incorporate this information. We implemented trans-acting GTP into a computational model for microtubule dynamics. In simulations, growing microtubules often exposed terminal GDP-bound subunits without undergoing catastrophe. Transient GDP exposure on the growing plus end slowed elongation by reducing the number of favorable binding sites on the microtubule end. Slower elongation led to erosion of the GTP cap and an increase in the frequency of catastrophe. Allowing GDP-to-GTP exchange on terminal subunits in simulations mitigated these effects. Using mutant αβ-tubulin or modified GTP, we showed experimentally that a more readily exchangeable nucleotide led to less frequent catastrophe. Current models for microtubule dynamics do not account for GDP-to-GTP exchange on the growing microtubule end, so our findings provide a new way of thinking about the molecular events that initiate catastrophe. © 2016 Piedra 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).

Evaluating big deal journal bundles.

Science.gov (United States)

Bergstrom, Theodore C; Courant, Paul N; McAfee, R Preston; Williams, Michael A

2014-07-01

Large commercial publishers sell bundled online subscriptions to their entire list of academic journals at prices significantly lower than the sum of their á la carte prices. Bundle prices differ drastically between institutions, but they are not publicly posted. The data that we have collected enable us to compare the bundle prices charged by commercial publishers with those of nonprofit societies and to examine the types of price discrimination practiced by commercial and nonprofit journal publishers. This information is of interest to economists who study monopolist pricing, librarians interested in making efficient use of library budgets, and scholars who are interested in the availability of the work that they publish.

Dimensional measurement of fresh fuel bundle for CANDU reactor

International Nuclear Information System (INIS)

Jo, Chang Keun; Cho, Moon Sung; Suk, Ho Chun; Koo, Dae Seo; Jun, Ji Su; Jung, Jong Yeob

2005-01-01

This report describes the results of the dimensional measurement of fresh fuel bundles for the CANDU reactor in order to estimate the integrity of fuel bundle in two-phase flow in the CANDU-6 fuel channel. The dimensional measurements of fuel bundles are performed by using the 'CANDU Fuel In-Bay Inspection and Dimensional Measurement System', which was developed by this project. The dimensional measurements are done from February 2004 to March 2004 in the CANDU fuel storage of KNFC for the 36 fresh fuel bundles, which are produced by KNFC and are waiting for the delivery to the Wolsong-3 plant. The detail items of dimensional measurements are included fuel rod and bearing pad profiles of the outer ring in fuel bundle, diameter of fuel bundle, bowing of fuel bundle, fuel rod length, and surface profile of end plate profile. The measurement data will be compared with those of the post-irradiated bundles cooled in Wolsong-3 NPP spent fuel pool by using the same bundles and In-Bay Measurement System. So, this analysis of data will be applied for the evaluation of fuel bundle integrity in two-phase flow of the CANDU-6 fuel channel

Sasakian and Parabolic Higgs Bundles

Science.gov (United States)

Biswas, Indranil; Mj, Mahan

2018-03-01

Let M be a quasi-regular compact connected Sasakian manifold, and let N = M/ S 1 be the base projective variety. We establish an equivalence between the class of Sasakian G-Higgs bundles over M and the class of parabolic (or equivalently, ramified) G-Higgs bundles over the base N.

Fuel bundle movement due to reverse flow

Energy Technology Data Exchange (ETDEWEB)

Wahba, N N; Akalin, O [Ontario Hydro, Toronto, ON (Canada)

1996-12-31

When a break occurs in the inlet feeder or inlet header, the rapid depressurization will cause the channel flow to reverse forcing the string of bundles to accelerate and impact with upstream shield plug. A model has been developed to predict the bundle motion due to the channel flow reversal. The model accounts for various forces acting on the bundle. A series of five reverse flow, bundle acceleration experiments have been conducted simulating a break in the inlet feeder of a CANDU fuel channel. The model has been validated against the experiments. The predicted impact velocities are in good agreement with the measured values. It is demonstrated that the model may be successfully used in predicting bundle relocation timing following a large LOCA (loss of coolant). (author). 7 refs., 3 tabs., 11 figs.

Bundles over Quantum RealWeighted Projective Spaces

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Tomasz Brzeziński

2012-09-01

Full Text Available The algebraic approach to bundles in non-commutative geometry and the definition of quantum real weighted projective spaces are reviewed. Principal U(1-bundles over quantum real weighted projective spaces are constructed. As the spaces in question fall into two separate classes, the negative or odd class that generalises quantum real projective planes and the positive or even class that generalises the quantum disc, so do the constructed principal bundles. In the negative case the principal bundle is proven to be non-trivial and associated projective modules are described. In the positive case the principal bundles turn out to be trivial, and so all the associated modules are free. It is also shown that the circle (coactions on the quantum Seifert manifold that define quantum real weighted projective spaces are almost free.

Dynamic behaviour of FBR fuel pin bundles

International Nuclear Information System (INIS)

Martin, P.H.; Van Dorsselaere, J.P.; Ravenet, A.

1990-01-01

A programme of shock tests on a fast neutron reactor subassembly model (SPX1 geometry) including a complete bundle of fuel pins (dummy elements) is being carried out in the BELIER test facility at Cadarache. The purpose of these tests is: to determine the distribution of dynamic forces applied to the fuel rod clads under the impact conditions encountered in a reactor during a earthquake; to reduce as much as possible the conservatism of the methods presently used for the calculation of those forces. The test programme, now being completed, consists of the following steps: impacts on the mock-up in air with an non-compact bundle (situation of the subassembly at beginning of life (BOL) with clearances within the bundle); impacts under the same conditions but with fluid (water) in the subassembly; impacts on the mock-up in air and with a compacted bundle (simulating the conditions of an end-of-life (EOL) bundle with no clearance within the bundle). The accelerations studied in these tests cover the range encountered in design calculations for the subassembly frequencies in beam mode. (author)

A computational framework for cortical microtubule dynamics in realistically shaped plant cells.

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Bandan Chakrabortty

2018-02-01

Full Text Available Plant morphogenesis is strongly dependent on the directional growth and the subsequent oriented division of individual cells. It has been shown that the plant cortical microtubule array plays a key role in controlling both these processes. This ordered structure emerges as the collective result of stochastic interactions between large numbers of dynamic microtubules. To elucidate this complex self-organization process a number of analytical and computational approaches to study the dynamics of cortical microtubules have been proposed. To date, however, these models have been restricted to two dimensional planes or geometrically simple surfaces in three dimensions, which strongly limits their applicability as plant cells display a wide variety of shapes. This limitation is even more acute, as both local as well as global geometrical features of cells are expected to influence the overall organization of the array. Here we describe a framework for efficiently simulating microtubule dynamics on triangulated approximations of arbitrary three dimensional surfaces. This allows the study of microtubule array organization on realistic cell surfaces obtained by segmentation of microscopic images. We validate the framework against expected or known results for the spherical and cubical geometry. We then use it to systematically study the individual contributions of global geometry, cell-edge induced catastrophes and cell-face induced stability to array organization in a cuboidal geometry. Finally, we apply our framework to analyze the highly non-trivial geometry of leaf pavement cells of Arabidopsis thaliana, Nicotiana benthamiana and Hedera helix. We show that our simulations can predict multiple features of the microtubule array structure in these cells, revealing, among others, strong constraints on the orientation of division planes.

A computational framework for cortical microtubule dynamics in realistically shaped plant cells

KAUST Repository

Chakrabortty, Bandan; Blilou, Ikram; Scheres, Ben; Mulder, Bela M.

2018-01-01

Plant morphogenesis is strongly dependent on the directional growth and the subsequent oriented division of individual cells. It has been shown that the plant cortical microtubule array plays a key role in controlling both these processes. This ordered structure emerges as the collective result of stochastic interactions between large numbers of dynamic microtubules. To elucidate this complex self-organization process a number of analytical and computational approaches to study the dynamics of cortical microtubules have been proposed. To date, however, these models have been restricted to two dimensional planes or geometrically simple surfaces in three dimensions, which strongly limits their applicability as plant cells display a wide variety of shapes. This limitation is even more acute, as both local as well as global geometrical features of cells are expected to influence the overall organization of the array. Here we describe a framework for efficiently simulating microtubule dynamics on triangulated approximations of arbitrary three dimensional surfaces. This allows the study of microtubule array organization on realistic cell surfaces obtained by segmentation of microscopic images. We validate the framework against expected or known results for the spherical and cubical geometry. We then use it to systematically study the individual contributions of global geometry, cell-edge induced catastrophes and cell-face induced stability to array organization in a cuboidal geometry. Finally, we apply our framework to analyze the highly non-trivial geometry of leaf pavement cells of Arabidopsis thaliana, Nicotiana benthamiana and Hedera helix. We show that our simulations can predict multiple features of the microtubule array structure in these cells, revealing, among others, strong constraints on the orientation of division planes.

A computational framework for cortical microtubule dynamics in realistically shaped plant cells

KAUST Repository

Chakrabortty, Bandan

2018-02-02

Plant morphogenesis is strongly dependent on the directional growth and the subsequent oriented division of individual cells. It has been shown that the plant cortical microtubule array plays a key role in controlling both these processes. This ordered structure emerges as the collective result of stochastic interactions between large numbers of dynamic microtubules. To elucidate this complex self-organization process a number of analytical and computational approaches to study the dynamics of cortical microtubules have been proposed. To date, however, these models have been restricted to two dimensional planes or geometrically simple surfaces in three dimensions, which strongly limits their applicability as plant cells display a wide variety of shapes. This limitation is even more acute, as both local as well as global geometrical features of cells are expected to influence the overall organization of the array. Here we describe a framework for efficiently simulating microtubule dynamics on triangulated approximations of arbitrary three dimensional surfaces. This allows the study of microtubule array organization on realistic cell surfaces obtained by segmentation of microscopic images. We validate the framework against expected or known results for the spherical and cubical geometry. We then use it to systematically study the individual contributions of global geometry, cell-edge induced catastrophes and cell-face induced stability to array organization in a cuboidal geometry. Finally, we apply our framework to analyze the highly non-trivial geometry of leaf pavement cells of Arabidopsis thaliana, Nicotiana benthamiana and Hedera helix. We show that our simulations can predict multiple features of the microtubule array structure in these cells, revealing, among others, strong constraints on the orientation of division planes.

GTSE1 is a microtubule plus-end tracking protein that regulates EB1-dependent cell migration.

Directory of Open Access Journals (Sweden)

Massimilano Scolz

Full Text Available The regulation of cell migration is a highly complex process that is often compromised when cancer cells become metastatic. The microtubule cytoskeleton is necessary for cell migration, but how microtubules and microtubule-associated proteins regulate multiple pathways promoting cell migration remains unclear. Microtubule plus-end binding proteins (+TIPs are emerging as important players in many cellular functions, including cell migration. Here we identify a +TIP, GTSE1, that promotes cell migration. GTSE1 accumulates at growing microtubule plus ends through interaction with the EB1+TIP. The EB1-dependent +TIP activity of GTSE1 is required for cell migration, as well as for microtubule-dependent disassembly of focal adhesions. GTSE1 protein levels determine the migratory capacity of both nontransformed and breast cancer cell lines. In breast cancers, increased GTSE1 expression correlates with invasive potential, tumor stage, and time to distant metastasis, suggesting that misregulation of GTSE1 expression could be associated with increased invasive potential.

Clostridium difficile toxin CDT induces formation of microtubule-based protrusions and increases adherence of bacteria.

Directory of Open Access Journals (Sweden)

Carsten Schwan

2009-10-01

Full Text Available Clostridium difficile causes antibiotic-associated diarrhea and pseudomembranous colitis by production of the Rho GTPase-glucosylating toxins A and B. Recently emerging hypervirulent Clostridium difficile strains additionally produce the binary ADP-ribosyltransferase toxin CDT (Clostridium difficile transferase, which ADP-ribosylates actin and inhibits actin polymerization. Thus far, the role of CDT as a virulence factor is not understood. Here we report by using time-lapse- and immunofluorescence microscopy that CDT and other binary actin-ADP-ribosylating toxins, including Clostridium botulinum C2 toxin and Clostridium perfringens iota toxin, induce redistribution of microtubules and formation of long (up to >150 microm microtubule-based protrusions at the surface of intestinal epithelial cells. The toxins increase the length of decoration of microtubule plus-ends by EB1/3, CLIP-170 and CLIP-115 proteins and cause redistribution of the capture proteins CLASP2 and ACF7 from microtubules at the cell cortex into the cell interior. The CDT-induced microtubule protrusions form a dense meshwork at the cell surface, which wrap and embed bacterial cells, thereby largely increasing the adherence of Clostridia. The study describes a novel type of microtubule structure caused by less efficient microtubule capture and offers a new perspective for the pathogenetic role of CDT and other binary actin-ADP-ribosylating toxins in host-pathogen interactions.

Magnolol Inhibits the Growth of Non-Small Cell Lung Cancer via Inhibiting Microtubule Polymerization

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Jia Shen

2017-07-01

Full Text Available Background: The tubulin/microtubule system, which is an integral component of the cytoskeleton, plays an essential role in mitosis. Targeting mitotic progression by disturbing microtubule dynamics is a rational strategy for cancer treatment. Methods: Microtubule polymerization assay was performed to examine the effect of Magnolol (a novel natural phenolic compound isolated from Magnolia obovata on cellular microtubule polymerization in human non-small cell lung cancer (NSCLC cells. Cell cycle analysis, mitotic index assay, cell proliferation assay, colony formation assay, western blotting analysis of cell cycle regulators, Annexin V-FITC/PI staining, and live/dead viability staining were carried out to investigate the Magnolol’s inhibitory effect on proliferation and viability of NSCLS cells in vitro. Xenograft model of human A549 NSCLC tumor was used to determine the Magnolol’s efficacy in vivo. Results: Magnolol treatment effectively inhibited cell proliferation and colony formation of NSCLC cells. Further study proved that Magnolol induced the mitotic phase arrest and inhibited G2/M progression in a dose-dependent manner, which were mechanistically associated with expression alteration of a series of cell cycle regulators. Furthermore, Magnolol treatment disrupted the cellular microtubule organization via inhibiting the polymerization of microtubule. We also found treatment with NSCLC cells with Magnolol resulted in apoptosis activation through a p53-independent pathway, and autophgy induction via down-regulation of the Akt/mTOR pathway. Finally, Magnolol treatment significantly suppressed the NSCLC tumor growth in mouse xenograft model in vivo. Conclusion: These findings identify Magnolol as a promising candidate with anti-microtubule polymerization activity for NSCLC treatment.

Diversity in the organization of elastin bundles and intramembranous muscles in bat wings.

Science.gov (United States)

Cheney, Jorn A; Allen, Justine J; Swartz, Sharon M

2017-04-01

Unlike birds and insects, bats fly with wings composed of thin skin that envelops the bones of the forelimb and spans the area between the limbs, digits, and sometimes the tail. This skin is complex and unusual; it is thinner than typical mammalian skin and contains organized bundles of elastin and embedded skeletal muscles. These elements are likely responsible for controlling the shape of the wing during flight and contributing to the aerodynamic capabilities of bats. We examined the arrangement of two macroscopic architectural elements in bat wings, elastin bundles and wing membrane muscles, to assess the diversity in bat wing skin morphology. We characterized the plagiopatagium and dactylopatagium of 130 species from 17 families of bats using cross-polarized light imaging. This method revealed structures with distinctive relative birefringence, heterogeneity of birefringence, variation in size, and degree of branching. We used previously published anatomical studies and tissue histology to identify birefringent structures, and we analyzed their architecture across taxa. Elastin bundles, muscles, neurovasculature, and collagenous fibers are present in all species. Elastin bundles are oriented in a predominantly spanwise or proximodistal direction, and there are five characteristic muscle arrays that occur within the plagiopatagium, far more muscle than typically recognized. These results inform recent functional studies of wing membrane architecture, support the functional hypothesis that elastin bundles aid wing folding and unfolding, and further suggest that all bats may use these architectural elements for flight. All species also possess numerous muscles within the wing membrane, but the architecture of muscle arrays within the plagiopatagium varies among families. To facilitate present and future discussion of these muscle arrays, we refine wing membrane muscle nomenclature in a manner that reflects this morphological diversity. The architecture of the

Fuel temperature characteristics of the 37-element and CANFLEX fuel bundle

International Nuclear Information System (INIS)

Bae, Jun Ho; Rho, Gyu Hong; Park, Joo Hwan

2009-10-01

This report describes the fuel temperature characteristics of CANFLEX fuel bundles and 37-element fuel bundles for a different burnup of fuel. The program was consisted for seeking the fuel temperature of fuel bundles of CANFLEX fuel bundles and 37-element fuel bundles by using the method in NUCIRC. Fuel temperature has an increasing pattern with the burnup of fuel for CANFLEX fuel bundles and 37-element fuel bundles. For all the case of burnup, the fuel temperature of CANFLEX fuel bundles has a lower value than that of 37-element fuel bundles. Especially, for the high power channel, the CANFLEX fuel bundles show a lower fuel temperature as much as about 75 degree, and the core averaged fuel temperature has a lower fuel temperature of about 50 degree than that of 37-element fuel bundles. The lower fuel temperature of CANFLEX fuel bundles is expected to enhance the safety by reducing the fuel temperature coefficient. Finally, for each burnup of CANFLEX fuel bundles and 37-element fuel bundles, the equation was present for predicting the fuel temperature of a bundle in terms of a coolant temperature and bundle power

A structural model for microtubule minus-end recognition and protection by CAMSAP proteins

NARCIS (Netherlands)

Atherton, Joseph; Jiang, Kai; Stangier, Marcel M.; Luo, Yanzhang; Hua, Shasha; Houben, Klaartje; Van Hooff, Jolien J.E.; Joseph, Agnel Praveen; Scarabelli, Guido; Grant, Barry J.; Roberts, Anthony J.; Topf, Maya; Steinmetz, Michel O.; Baldus, Marc; Moores, Carolyn A.; Akhmanova, Anna

2017-01-01

CAMSAP and Patronin family members regulate microtubule minus-end stability and localization and thus organize noncentrosomal microtubule networks, which are essential for cell division, polarization and differentiation. Here, we found that the CAMSAP C-terminal CKK domain is widely present among

Episodic payments (bundling): PART I.

Science.gov (United States)

Jacofsky, D J

2017-10-01

Episodic, or bundled payments, is a concept now familiar to most in the healthcare arena, but the models are often misunderstood. Under a traditional fee-for-service model, each provider bills separately for their services which creates financial incentives to maximise volumes. Under a bundled payment, a single entity, often referred to as a convener (maybe the hospital, the physician group, or a third party) assumes the risk through a payer contract for all services provided within a defined episode of care, and receives a single (bundled) payment for all services provided for that episode. The time frame around the intervention is variable, but defined in advance, as are included and excluded costs. Timing of the actual payment in a bundle may either be before the episode occurs (prospective payment model), or after the end of the episode through a reconciliation (retrospective payment model). In either case, the defined costs over the defined time frame are borne by the convener. Cite this article: Bone Joint J 2017;99-B:1280-5. ©2017 The British Editorial Society of Bone & Joint Surgery.

The growth speed of microtubules with XMAP215-coated beads coupled to their ends is increased by tensile force

Science.gov (United States)

Trushko, Anastasiya; Schäffer, Erik; Howard, Jonathon

2013-01-01

The generation of pulling and pushing forces is one of the important functions of microtubules, which are dynamic and polarized structures. The ends of dynamic microtubules are able to form relatively stable links to cellular structures, so that when a microtubule grows it can exert a pushing force and when it shrinks it can exert a pulling force. Microtubule growth and shrinkage are tightly regulated by microtubule-associated proteins (MAPs) that bind to microtubule ends. Given their localization, MAPs may be exposed to compressive and tensile forces. The effect of such forces on MAP function, however, is poorly understood. Here we show that beads coated with the microtubule polymerizing protein XMAP215, the Xenopus homolog of Dis1 and chTOG, are able to link stably to the plus ends of microtubules, even when the ends are growing or shrinking; at growing ends, the beads increase the polymerization rate. Using optical tweezers, we found that tensile force further increased the microtubule polymerization rate. These results show that physical forces can regulate the activity of MAPs. Furthermore, our results show that XMAP215 can be used as a handle to sense and mechanically manipulate the dynamics of the microtubule tip. PMID:23964126

Equilibrium polyelectrolyte bundles with different multivalent counterion concentrations

Science.gov (United States)

Sayar, Mehmet; Holm, Christian

2010-09-01

We present the results of molecular-dynamics simulations on the salt concentration dependence of the formation of polyelectrolyte bundles in thermodynamic equilibrium. Extending our results on salt-free systems we investigate here deficiency or excess of trivalent counterions in solution. Our results reveal that the trivalent counterion concentration significantly alters the bundle size and size distribution. The onset of bundle formation takes place at earlier Bjerrum length values with increasing trivalent counterion concentration. For the cases of 80%, 95%, and 100% charge compensation via trivalent counterions, the net charge of the bundles decreases with increasing size. We suggest that competition among two different mechanisms, counterion condensation and merger of bundles, leads to a nonmonotonic change in line-charge density with increasing Bjerrum length. The investigated case of having an abundance of trivalent counterions by 200% prohibits such a behavior. In this case, we find that the difference in effective line-charge density of different size bundles diminishes. In fact, the system displays an isoelectric point, where all bundles become charge neutral.

Effects of ultraviolet radiation on microtubule organisation and morphogenesis in plants

Energy Technology Data Exchange (ETDEWEB)

Staxen, I.

1994-09-01

The involvement of the cytoskeleton in the development of somatic embryos was studied in Larix x eurolepis. Protoplasts were isolated from both somatic embryo-regenerating and non-generating cultures and fractionated on a discontinuous Percoll density gradient. Protoplasts of two cell lines of Larix eurolepis, one with regenerating potential and one lacking this potential, were compared. In contrast to the non-regenerating line were a protoplast-like organisation of the cortical microtubules was maintained, re-organisation of this microtubular network occurred in the regenerable line after only three days of culture, indicating that organised growth was occurring. However, this early organisation of cortical microtubules may not always be a valid marker for regenerable and non-regenerable material. In order to investigate the effect of ultraviolet-B (UV-B, 280-320 nm) radiation on the microtubule cytoskeleton, protoplasts were isolated from leaves of Petunia hybrida and subjected to four different doses of UV-B radiation. The organisation of the microtubules and the progression of the cells through the cell cycle was observed at 0, 24, 48 and 72 h after irradiation. UV-B induced breaks in the cortical microtubules resulting in shorter fragments with increasing amounts of radiation. Also, the division of the protoplasts was delayed. Whole Petunia plants were grown in growth chambers in the presence and absence of UV-B. The plants responded to UV-B with increased rates of CO{sub 2} assimilation, a 60% increase in UV-screening compounds and the changes in the morphology of the leaves that were reflected in a 70-100% increase in leaf area and 20% decrease in leaf thickness. The microtubules of the epidermal cells was not affected by UV-B, nor was the number of epidermal cells (per unit area). The increase in leaf area in the UV-treated plants appeared due to stimulation of cell division in the leaf meristems. 111 refs, 5 figs, 2 tabs.

Kinesin-8 effects on mitotic microtubule dynamics contribute to spindle function in fission yeast

Science.gov (United States)

Gergely, Zachary R.; Crapo, Ammon; Hough, Loren E.; McIntosh, J. Richard; Betterton, Meredith D.

2016-01-01

Kinesin-8 motor proteins destabilize microtubules. Their absence during cell division is associated with disorganized mitotic chromosome movements and chromosome loss. Despite recent work studying effects of kinesin-8s on microtubule dynamics, it remains unclear whether the kinesin-8 mitotic phenotypes are consequences of their effect on microtubule dynamics, their well-established motor activity, or additional, unknown functions. To better understand the role of kinesin-8 proteins in mitosis, we studied the effects of deletion of the fission yeast kinesin-8 proteins Klp5 and Klp6 on chromosome movements and spindle length dynamics. Aberrant microtubule-driven kinetochore pushing movements and tripolar mitotic spindles occurred in cells lacking Klp5 but not Klp6. Kinesin-8–deletion strains showed large fluctuations in metaphase spindle length, suggesting a disruption of spindle length stabilization. Comparison of our results from light microscopy with a mathematical model suggests that kinesin-8–induced effects on microtubule dynamics, kinetochore attachment stability, and sliding force in the spindle can explain the aberrant chromosome movements and spindle length fluctuations seen. PMID:27146110

Prickle isoforms control the direction of tissue polarity by microtubule independent and dependent mechanisms

Directory of Open Access Journals (Sweden)

Katherine A. Sharp

2016-03-01

Full Text Available Planar cell polarity signaling directs the polarization of cells within the plane of many epithelia. While these tissues exhibit asymmetric localization of a set of core module proteins, in Drosophila, more than one mechanism links the direction of core module polarization to the tissue axes. One signaling system establishes a polarity bias in the parallel, apical microtubules upon which vesicles containing core proteins traffic. Swapping expression of the differentially expressed Prickle isoforms, Prickle and Spiny-legs, reverses the direction of core module polarization. Studies in the proximal wing and the anterior abdomen indicated that this results from their differential control of microtubule polarity. Prickle and Spiny-legs also control the direction of polarization in the distal wing (D-wing and the posterior abdomen (P-abd. We report here that this occurs without affecting microtubule polarity in these tissues. The direction of polarity in the D-wing is therefore likely determined by a novel mechanism independent of microtubule polarity. In the P-abd, Prickle and Spiny-legs interpret at least two directional cues through a microtubule-polarity-independent mechanism.

Dietary flavonoid fisetin binds to β-tubulin and disrupts microtubule dynamics in prostate cancer cells

OpenAIRE

Mukhtar, Eiman; Adhami, Vaqar Mustafa; Sechi, Mario; Mukhtar, Hasan

2015-01-01

Microtubule targeting based therapies have revolutionized cancer treatment; however, resistance and side effects remain a major limitation. Therefore, novel strategies that can overcome these limitations are urgently needed. We made a novel discovery that fisetin, a hydroxyflavone, is a microtubule stabilizing agent. Fisetin binds to tubulin and stabilizes microtubules with binding characteristics far superior than paclitaxel. Surface plasmon resonance and computational docking studies sugges...

Atomic-resolution structure of the CAP-Gly domain of dynactin on polymeric microtubules determined by magic angle spinning NMR spectroscopy.

Science.gov (United States)

Yan, Si; Guo, Changmiao; Hou, Guangjin; Zhang, Huilan; Lu, Xingyu; Williams, John Charles; Polenova, Tatyana

2015-11-24

Microtubules and their associated proteins perform a broad array of essential physiological functions, including mitosis, polarization and differentiation, cell migration, and vesicle and organelle transport. As such, they have been extensively studied at multiple levels of resolution (e.g., from structural biology to cell biology). Despite these efforts, there remain significant gaps in our knowledge concerning how microtubule-binding proteins bind to microtubules, how dynamics connect different conformational states, and how these interactions and dynamics affect cellular processes. Structures of microtubule-associated proteins assembled on polymeric microtubules are not known at atomic resolution. Here, we report a structure of the cytoskeleton-associated protein glycine-rich (CAP-Gly) domain of dynactin motor on polymeric microtubules, solved by magic angle spinning NMR spectroscopy. We present the intermolecular interface of CAP-Gly with microtubules, derived by recording direct dipolar contacts between CAP-Gly and tubulin using double rotational echo double resonance (dREDOR)-filtered experiments. Our results indicate that the structure adopted by CAP-Gly varies, particularly around its loop regions, permitting its interaction with multiple binding partners and with the microtubules. To our knowledge, this study reports the first atomic-resolution structure of a microtubule-associated protein on polymeric microtubules. Our approach lays the foundation for atomic-resolution structural analysis of other microtubule-associated motors.

Actin and microtubule networks contribute differently to cell response for small and large strains

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Kubitschke, H.; Schnauss, J.; Nnetu, K. D.; Warmt, E.; Stange, R.; Kaes, J.

2017-09-01

Cytoskeletal filaments provide cells with mechanical stability and organization. The main key players are actin filaments and microtubules governing a cell’s response to mechanical stimuli. We investigated the specific influences of these crucial components by deforming MCF-7 epithelial cells at small (≤5% deformation) and large strains (>5% deformation). To understand specific contributions of actin filaments and microtubules, we systematically studied cellular responses after treatment with cytoskeleton influencing drugs. Quantification with the microfluidic optical stretcher allowed capturing the relative deformation and relaxation of cells under different conditions. We separated distinctive deformational and relaxational contributions to cell mechanics for actin and microtubule networks for two orders of magnitude of drug dosages. Disrupting actin filaments via latrunculin A, for instance, revealed a strain-independent softening. Stabilizing these filaments by treatment with jasplakinolide yielded cell softening for small strains but showed no significant change at large strains. In contrast, cells treated with nocodazole to disrupt microtubules displayed a softening at large strains but remained unchanged at small strains. Stabilizing microtubules within the cells via paclitaxel revealed no significant changes for deformations at small strains, but concentration-dependent impact at large strains. This suggests that for suspended cells, the actin cortex is probed at small strains, while at larger strains; the whole cell is probed with a significant contribution from the microtubules.

Annular burnout data from rod-bundle experiments

International Nuclear Information System (INIS)

Yoder, G.L.; Morris, D.G.; Mullins, C.B.

1983-01-01

Burnout data for annular flow in a rod bundle are presented for both transient and steady-state conditions. Tests were performed at the Oak Ridge National Laboratory in the Thermal Hydraulic Test Facility (THTF), a pressurized-water loop containing an electrically heated 64-rod bundle. The bundle configuration is typical of later generation pressurized-water reactors with 17 x 17 fuel arrays. Both axial and radial power profiles are flat. All experiments were carried out in upflow with subcooled inlet conditions, insuring accurate flow measurement. Conditions within the bundle were typical of those which could be encountered during a nuclear reactor loss-of-coolant accident

Reassessing the roles of PIN proteins and anticlinal microtubules during pavement cell morphogenesis

Energy Technology Data Exchange (ETDEWEB)

Belteton, Samuel; Sawchuk, Megan G.; Donohoe, Bryon S.; Scarpella, Enrico; Szymanski, Daniel B.

2017-11-30

The leaf epidermis is a biomechanical shell that influences the size and shape of the organ. Its morphogenesis is a multiscale process in which nanometer-scale cytoskeletal protein complexes, individual cells, and groups of cells pattern growth and define macroscopic leaf traits. Interdigitated growth of neighboring cells is an evolutionarily conserved developmental strategy. Understanding how signaling pathways and cytoskeletal proteins pattern cell walls during this form of tissue morphogenesis is an important research challenge. The cellular and molecular control of a lobed cell morphology is currently thought to involve PIN-FORMED (PIN)-type plasma membrane efflux carriers that generate subcellular auxin gradients. Auxin gradients were proposed to function across cell boundaries to encode stable offset patterns of cortical microtubules and actin filaments between adjacent cells. Many models suggest that long-lived microtubules along the anticlinal cell wall generate local cell wall heterogeneities that restrict local growth and specify the timing and location of lobe formation. Here we used Arabidopsis reverse genetics and multivariate long-term time-lapse imaging to test current cell shape control models. We found that neither PIN proteins nor microtubules along the anticlinal wall predict the patterns of lobe formation. In fields of lobing cells, anticlinal microtubules are not correlated with cell shape and are unstable at the time scales of cell expansion. Our analyses indicate that anticlinal microtubules have multiple functions in pavement cells, and that lobe initiation is likely controlled by complex interactions among cell geometry, cell wall stress patterns, and transient microtubule networks that span the anticlinal and periclinal walls.

Implementing the awakening and breathing coordination, delirium monitoring/management, and early exercise/mobility bundle into everyday care: opportunities, challenges, and lessons learned for implementing the ICU Pain, Agitation, and Delirium Guidelines.

Science.gov (United States)

Balas, Michele C; Burke, William J; Gannon, David; Cohen, Marlene Z; Colburn, Lois; Bevil, Catherine; Franz, Doug; Olsen, Keith M; Ely, E Wesley; Vasilevskis, Eduard E

2013-09-01

The awakening and breathing coordination, delirium monitoring/management, and early exercise/mobility bundle is an evidence-based interprofessional multicomponent strategy for minimizing sedative exposure, reducing duration of mechanical ventilation, and managing ICU-acquired delirium and weakness. The purpose of this study was to identify facilitators and barriers to awakening and breathing coordination, delirium monitoring/management, and early exercise/mobility bundle adoption and to evaluate the extent to which bundle implementation was effective, sustainable, and conducive to dissemination. Prospective, before-after, mixed-methods study. Five adult ICUs, one step-down unit, and a special care unit located in a 624-bed academic medical center : Interprofessional ICU team members at participating institution. In collaboration with the participating institution, we developed, implemented, and refined an awakening and breathing coordination, delirium monitoring/management, and early exercise/mobility bundle policy. Over the course of an 18-month period, all ICU team members were offered the opportunity to participate in numerous multimodal educational efforts. Three focus group sessions, three online surveys, and one educational evaluation were administered in an attempt to identify facilitators and barriers to bundle adoption. Factors believed to facilitate bundle implementation included: 1) the performance of daily, interdisciplinary, rounds; 2) engagement of key implementation leaders; 3) sustained and diverse educational efforts; and 4) the bundle's quality and strength. Barriers identified included: 1) intervention-related issues (e.g., timing of trials, fear of adverse events), 2) communication and care coordination challenges, 3) knowledge deficits, 4) workload concerns, and 5) documentation burden. Despite these challenges, participants believed implementation ultimately benefited patients, improved interdisciplinary communication, and empowered nurses and

Direct incorporation of guanosine 5'-diphosphate into microtubules without guanosine 5'-triphosphate hydrolysis

International Nuclear Information System (INIS)

Hamel, E.; Batra, J.K.; Lin, C.M.

1986-01-01

Using highly purified calf brain tubulin bearing [8- 14 C]guanosine 5'-diphosphate (GDP) in the exchangeable nucleotide site and heat-treated microtubule-associated proteins, the authors have found that a significant proportion of exchangeable-site GDP in microtubules can be incorporated directly during guanosine 5'-triphosphate (GTP) dependent polymerization of tubulin, without an initial exchange of GDP for GTP and subsequent GTP hydrolysis during assembly. The precise amount of GDP incorporated directly into microtubules is highly dependent on specific reaction conditions, being favored by high tubulin concentrations, low GTP and Mg 2+ concentrations, and exogenous GDP in the reaction mixture. Minimum effects were observed with changes in reaction pH or temperature, changes in concentration of microtubule-associated proteins, alteration of the sulfonate buffer, or the presence of a calcium chelator in the reaction mixture. Under conditions most favorable for direct GDP incorporation, about one-third of the GDP in microtubules is incorporated directly (without GTP hydrolysis) and two-thirds is incorporated hydrolytically (as a consequence of GTP hydrolysis). Direct incorporation of GDP occurs in a constant proportion throughout elongation, and the amount of direct incorporation probably reflects the rapid equilibration of GDP and GTP at the exchangeable site that occurs before the onset of assembly

Monoubiquitination Inhibits the Actin Bundling Activity of Fascin.

Science.gov (United States)

Lin, Shengchen; Lu, Shuang; Mulaj, Mentor; Fang, Bin; Keeley, Tyler; Wan, Lixin; Hao, Jihui; Muschol, Martin; Sun, Jianwei; Yang, Shengyu

2016-12-30

Fascin is an actin bundling protein that cross-links individual actin filaments into straight, compact, and stiff bundles, which are crucial for the formation of filopodia, stereocillia, and other finger-like membrane protrusions. The dysregulation of fascin has been implicated in cancer metastasis, hearing loss, and blindness. Here we identified monoubiquitination as a novel mechanism that regulates fascin bundling activity and dynamics. The monoubiquitination sites were identified to be Lys 247 and Lys 250 , two residues located in a positive charge patch at the actin binding site 2 of fascin. Using a chemical ubiquitination method, we synthesized chemically monoubiquitinated fascin and determined the effects of monoubiquitination on fascin bundling activity and dynamics. Our data demonstrated that monoubiquitination decreased the fascin bundling EC 50 , delayed the initiation of bundle assembly, and accelerated the disassembly of existing bundles. By analyzing the electrostatic properties on the solvent-accessible surface of fascin, we proposed that monoubiquitination introduced steric hindrance to interfere with the interaction between actin filaments and the positively charged patch at actin binding site 2. We also identified Smurf1 as a E3 ligase regulating the monoubiquitination of fascin. Our findings revealed a previously unidentified regulatory mechanism for fascin, which will have important implications for the understanding of actin bundle regulation under physiological and pathological conditions. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Monoubiquitination Inhibits the Actin Bundling Activity of Fascin*

Science.gov (United States)

Lin, Shengchen; Lu, Shuang; Mulaj, Mentor; Fang, Bin; Keeley, Tyler; Wan, Lixin; Hao, Jihui; Muschol, Martin; Sun, Jianwei; Yang, Shengyu

2016-01-01

Fascin is an actin bundling protein that cross-links individual actin filaments into straight, compact, and stiff bundles, which are crucial for the formation of filopodia, stereocillia, and other finger-like membrane protrusions. The dysregulation of fascin has been implicated in cancer metastasis, hearing loss, and blindness. Here we identified monoubiquitination as a novel mechanism that regulates fascin bundling activity and dynamics. The monoubiquitination sites were identified to be Lys247 and Lys250, two residues located in a positive charge patch at the actin binding site 2 of fascin. Using a chemical ubiquitination method, we synthesized chemically monoubiquitinated fascin and determined the effects of monoubiquitination on fascin bundling activity and dynamics. Our data demonstrated that monoubiquitination decreased the fascin bundling EC50, delayed the initiation of bundle assembly, and accelerated the disassembly of existing bundles. By analyzing the electrostatic properties on the solvent-accessible surface of fascin, we proposed that monoubiquitination introduced steric hindrance to interfere with the interaction between actin filaments and the positively charged patch at actin binding site 2. We also identified Smurf1 as a E3 ligase regulating the monoubiquitination of fascin. Our findings revealed a previously unidentified regulatory mechanism for fascin, which will have important implications for the understanding of actin bundle regulation under physiological and pathological conditions. PMID:27879315

Heat Transfer Analysis in Wire Bundles for Aerospace Vehicles

Science.gov (United States)

Rickman, S. L.; Iamello, C. J.

2016-01-01

Design of wiring for aerospace vehicles relies on an understanding of "ampacity" which refers to the current carrying capacity of wires, either, individually or in wire bundles. Designers rely on standards to derate allowable current flow to prevent exceedance of wire temperature limits due to resistive heat dissipation within the wires or wire bundles. These standards often add considerable margin and are based on empirical data. Commercial providers are taking an aggressive approach to wire sizing which challenges the conventional wisdom of the established standards. Thermal modelling of wire bundles may offer significant mass reduction in a system if the technique can be generalized to produce reliable temperature predictions for arbitrary bundle configurations. Thermal analysis has been applied to the problem of wire bundles wherein any or all of the wires within the bundle may carry current. Wire bundles present analytical challenges because the heat transfer path from conductors internal to the bundle is tortuous, relying on internal radiation and thermal interface conductance to move the heat from within the bundle to the external jacket where it can be carried away by convective and radiative heat transfer. The problem is further complicated by the dependence of wire electrical resistivity on temperature. Reduced heat transfer out of the bundle leads to higher conductor temperatures and, hence, increased resistive heat dissipation. Development of a generalized wire bundle thermal model is presented and compared with test data. The steady state heat balance for a single wire is derived and extended to the bundle configuration. The generalized model includes the effects of temperature varying resistance, internal radiation and thermal interface conductance, external radiation and temperature varying convective relief from the free surface. The sensitivity of the response to uncertainties in key model parameters is explored using Monte Carlo analysis.

Single-phase convective heat transfer in rod bundles

International Nuclear Information System (INIS)

Holloway, Mary V.; Beasley, Donald E.; Conner, Michael E.

2008-01-01

The convective heat transfer for turbulent flow through rod bundles representative of nuclear fuel rods used in pressurized water reactors is examined. The rod bundles consist of a square array of parallel rods that are held on a constant pitch by support grids spaced axially along the rod bundle. Split-vane pair support grids, which create swirling flow in the rod bundle, as well as disc and standard support grids are investigated. Single-phase convective heat transfer coefficients are measured for flow downstream of support grids in a rod bundle. The rods are heated using direct resistance heating, and a bulk axial flow of air is used to cool the rods in the rod bundle. Air is used as the working fluid instead of water to reduce the power required to heat the rod bundle. Results indicate heat transfer enhancement for up to 10 hydraulic diameters downstream of the support grids. A general correlation is developed to predict the heat transfer development downstream of support grids. In addition, circumferential variations in heat transfer coefficients result in hot streaks that develop on the rods downstream of split-vane pair support grids

Single-phase convective heat transfer in rod bundles

Energy Technology Data Exchange (ETDEWEB)

Holloway, Mary V. [Mechanical Engineering Department, United States Naval Academy, 590 Holloway Rd., Annapolis, MD 21402 (United States)], E-mail: holloway@usna.edu; Beasley, Donald E. [Mechanical Engineering Department, Clemson University, Clemson, SC 29634 (United States); Conner, Michael E. [Westinghouse Nuclear Fuel, 5801 Bluff Road, Columbia, SC 29250 (United States)

2008-04-15

The convective heat transfer for turbulent flow through rod bundles representative of nuclear fuel rods used in pressurized water reactors is examined. The rod bundles consist of a square array of parallel rods that are held on a constant pitch by support grids spaced axially along the rod bundle. Split-vane pair support grids, which create swirling flow in the rod bundle, as well as disc and standard support grids are investigated. Single-phase convective heat transfer coefficients are measured for flow downstream of support grids in a rod bundle. The rods are heated using direct resistance heating, and a bulk axial flow of air is used to cool the rods in the rod bundle. Air is used as the working fluid instead of water to reduce the power required to heat the rod bundle. Results indicate heat transfer enhancement for up to 10 hydraulic diameters downstream of the support grids. A general correlation is developed to predict the heat transfer development downstream of support grids. In addition, circumferential variations in heat transfer coefficients result in hot streaks that develop on the rods downstream of split-vane pair support grids.

Cost-effectiveness of a central venous catheter care bundle.

Directory of Open Access Journals (Sweden)

Kate A Halton

Full Text Available BACKGROUND: A bundled approach to central venous catheter care is currently being promoted as an effective way of preventing catheter-related bloodstream infection (CR-BSI. Consumables used in the bundled approach are relatively inexpensive which may lead to the conclusion that the bundle is cost-effective. However, this fails to consider the nontrivial costs of the monitoring and education activities required to implement the bundle, or that alternative strategies are available to prevent CR-BSI. We evaluated the cost-effectiveness of a bundle to prevent CR-BSI in Australian intensive care patients. METHODS AND FINDINGS: A Markov decision model was used to evaluate the cost-effectiveness of the bundle relative to remaining with current practice (a non-bundled approach to catheter care and uncoated catheters, or use of antimicrobial catheters. We assumed the bundle reduced relative risk of CR-BSI to 0.34. Given uncertainty about the cost of the bundle, threshold analyses were used to determine the maximum cost at which the bundle remained cost-effective relative to the other approaches to infection control. Sensitivity analyses explored how this threshold alters under different assumptions about the economic value placed on bed-days and health benefits gained by preventing infection. If clinicians are prepared to use antimicrobial catheters, the bundle is cost-effective if national 18-month implementation costs are below $1.1 million. If antimicrobial catheters are not an option the bundle must cost less than $4.3 million. If decision makers are only interested in obtaining cash-savings for the unit, and place no economic value on either the bed-days or the health benefits gained through preventing infection, these cost thresholds are reduced by two-thirds. CONCLUSIONS: A catheter care bundle has the potential to be cost-effective in the Australian intensive care setting. Rather than anticipating cash-savings from this intervention, decision

In-pool damaged fuel bundle recovery

International Nuclear Information System (INIS)

Piascik, T.G.; Patenaude, R.S.

1988-01-01

While preparing to rerack the Oyster Creek Nuclear Generating Station, GPU Nuclear had need to move a damaged fuel bundle. This bundle had no upper tie plate and could not be moved in the normal manner. GPU Nuclear formed a small, dedicated project team to disassemble, package, and move this damaged bundle. The team was composed of key personnel from GPU Nuclear Fuels Projects, OCNGS Operations and Proto-Power/Bisco, a specialty contractor who has fuel bundle reconstitution and rod consolidation experience, remote tooling, underwater video systems and experienced technicians. Proven tooling, clear procedures and a simple approach were important, but the key element was the spirit of teamwork and leadership exhibited by the people involved. In spite of several emergent problems which a task of this nature presents, this small, close knit utility/vendor team completed the work on schedule and within the exposure and cost budgets

CEP295 interacts with microtubules and is required for centriole elongation.

Science.gov (United States)

Chang, Ching-Wen; Hsu, Wen-Bin; Tsai, Jhih-Jie; Tang, Chieh-Ju C; Tang, Tang K

2016-07-01

Centriole duplication is a tightly ordered process during which procentrioles are assembled in G1-S and elongate during S and G2. Here, we show that human CEP295 (Drosophila Ana1) is not essential for initial cartwheel assembly, but is required to build distal half centrioles during S and G2. Using super-resolution and immunogold electron microscopy, we demonstrate that CEP295 is recruited to the proximal end of procentrioles in early S phase, when it is also localized at the centriolar microtubule wall that surrounds the human SAS6 cartwheel hub. Interestingly, depletion of CEP295 not only inhibits the recruitments of POC5 and POC1B to the distal half centrioles in G2, resulting in shorter centrioles, it also blocks the post-translational modification of centriolar microtubules (e.g. acetylation and glutamylation). Importantly, our results indicate that CEP295 directly interacts with microtubules, and that excess CEP295 could induce the assembly of overly long centrioles. Furthermore, exogenous expression of the N-terminal domain of CEP295 exerts a dominant-negative effect on centriole elongation. Collectively, these findings suggest that CEP295 is essential for building the distal half centrioles and for post-translational modification of centriolar microtubules. © 2016. Published by The Company of Biologists Ltd.

Challenges and opportunities in the high-resolution cryo-EM visualization of microtubules and their binding partners.

Science.gov (United States)

Nogales, Eva; Kellogg, Elizabeth H

2017-10-01

As non-crystallizable polymers, microtubules have been the target of cryo-electron microscopy (cryo-EM) studies since the technique was first established. Over the years, image processing strategies have been developed that take care of the unique, pseudo-helical symmetry of the microtubule. With recent progress in data quality and data processing, cryo-EM reconstructions are now reaching resolutions that allow the generation of atomic models of microtubules and the factors that bind them. These include cellular partners that contribute to microtubule cellular functions, or small ligands that interfere with those functions in the treatment of cancer. The stage is set to generate a family portrait for all identified microtubule interacting proteins and to use cryo-EM as a drug development tool in the targeting of tubulin. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Dissecting the nanoscale distributions and functions of microtubule-end-binding proteins EB1 and ch-TOG in interphase HeLa cells.

Directory of Open Access Journals (Sweden)

Satoko Nakamura

Full Text Available Recently, the EB1 and XMAP215/TOG families of microtubule binding proteins have been demonstrated to bind autonomously to the growing plus ends of microtubules and regulate their behaviour in in vitro systems. However, their functional redundancy or difference in cells remains obscure. Here, we compared the nanoscale distributions of EB1 and ch-TOG along microtubules using high-resolution microscopy techniques, and also their roles in microtubule organisation in interphase HeLa cells. The ch-TOG accumulation sites protruded ∼100 nm from the EB1 comets. Overexpression experiments showed that ch-TOG and EB1 did not interfere with each other's localisation, confirming that they recognise distinct regions at the ends of microtubules. While both EB1 and ch-TOG showed similar effects on microtubule plus end dynamics and additively increased microtubule dynamicity, only EB1 exhibited microtubule-cell cortex attachment activity. These observations indicate that EB1 and ch-TOG regulate microtubule organisation differently via distinct regions in the plus ends of microtubules.

Comparison of ASSERT subchannel code with Marviken bundle data

International Nuclear Information System (INIS)

Tahir, A.; Carver, M.B.

1984-04-01

In this paper ASSERT predictions are compared with the Marviken 6-rod bundle and 36+1 rod bundle. The predictions are presented for two experiments in the 6-rod bundle and four experiments in the 36+1 rod bundle. For low inlet subcooling, the void predictions are in good agreement with the experimental data. For high inlet subcooling, however, the agreement is not as good. This is attributed to the fact that in the high inlet subcooling experiments, single phase turbulent mixing plays a more important role in determining flow conditions in the bundle

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

Science.gov (United States)

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

2016-10-06

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 neurodevelopmental and neurodegenerative disorders. Growing evidence suggests that altered microtubule dynamics may also underlie or contribute to neurodevelopmental disorders and neurodegeneration. We report that biallelic mutations in TBCD, encoding one of the five co-chaperones required for assembly and disassembly of the αβ-tubulin heterodimer, the structural unit of microtubules, cause a disease with neurodevelopmental and neurodegenerative features characterized by early-onset cortical atrophy, secondary hypomyelination, microcephaly, thin corpus callosum, developmental delay, intellectual disability, seizures, optic atrophy, and spastic quadriplegia. Molecular dynamics simulations predicted long-range and/or local structural perturbations associated with the disease-causing mutations. Biochemical analyses documented variably reduced levels of TBCD, indicating relative instability of mutant proteins, and defective β-tubulin binding in a subset of the tested mutants. Reduced or defective TBCD function resulted in decreased soluble α/β-tubulin levels and accelerated microtubule polymerization in fibroblasts from affected subjects, demonstrating an overall shift toward a more rapidly growing and stable microtubule population. These cells displayed an aberrant mitotic spindle with disorganized, tangle-shaped microtubules and reduced aster formation, which however did not alter appreciably the rate of cell proliferation. Our findings establish that defective TBCD function underlies a recognizable encephalopathy and drives accelerated microtubule polymerization and enhanced microtubule stability, underscoring an additional cause of altered microtubule dynamics with

Stabilization of microtubules by inorganic phosphate and its structural analogues, the fluoride complexes of aluminum and beryllium

International Nuclear Information System (INIS)

Carlier, M.F.; Didry, D.; Melki, R.; Chabre, M.; Pantaloni, D.

1988-01-01

In order to elucidate how the elementary reactions of GTP cleavage and subsequent inorganic phosphate (P/sub i/) release, which accompany microtubule assembly, regulate microtubule dynamics, the effect of P/sub i/ and of its structural analogues AlF 4 - and BeF 3 - on the stability of GDP-microtubules has been investigated. Inorganic phosphate binds to microtubules with a low affinity (K/sub D/ = 25 mM) and slows down the rate of GDP-subunit dissociation by about 2 orders of magnitude. AlF 4 - and BeF 3 - exhibit phosphate-like effects with 1000-fold higher affinity. Evidence has been obtained for direct binding of BeF 3 - to microtubules with a stoichiometry of 1 mol of BeF 3 - per mole of GDP-subunit and an equilibrium dissociation constant of 12-15 μM. AlF 4 - and P/sub i/ compete for this site. Phosphate analogues abolish oscillatory polymerization kinetics and slow down microtubule turnover at steady state. In view of these results, the authors propose that P/sub i/ and its structural analogues bind to the site of the γ-phosphate of GTP in the E site and reconstitute a GDP-P/sub i/-microtubule, from which tubulin subunits dissociate very slowly. They therefore understand that, following GTP cleavage on microtubules, P/sub i/ release in the medium is accompanied by a structural change resulting in a large destabilization of the polymer. A cap of slowly dissociating GDP-P/sub i/-subunits prevents depolymerization of the microtubule GDP-core at steady state. The similarity with the actin system is studied

Reassessing the Roles of PIN Proteins and Anticlinal Microtubules during Pavement Cell Morphogenesis.

Science.gov (United States)

Belteton, Samuel A; Sawchuk, Megan G; Donohoe, Bryon S; Scarpella, Enrico; Szymanski, Daniel B

2018-01-01

The leaf epidermis is a biomechanical shell that influences the size and shape of the organ. Its morphogenesis is a multiscale process in which nanometer-scale cytoskeletal protein complexes, individual cells, and groups of cells pattern growth and define macroscopic leaf traits. Interdigitated growth of neighboring cells is an evolutionarily conserved developmental strategy. Understanding how signaling pathways and cytoskeletal proteins pattern cell walls during this form of tissue morphogenesis is an important research challenge. The cellular and molecular control of a lobed cell morphology is currently thought to involve PIN-FORMED (PIN)-type plasma membrane efflux carriers that generate subcellular auxin gradients. Auxin gradients were proposed to function across cell boundaries to encode stable offset patterns of cortical microtubules and actin filaments between adjacent cells. Many models suggest that long-lived microtubules along the anticlinal cell wall generate local cell wall heterogeneities that restrict local growth and specify the timing and location of lobe formation. Here, we used Arabidopsis ( Arabidopsis thaliana ) reverse genetics and multivariate long-term time-lapse imaging to test current cell shape control models. We found that neither PIN proteins nor long-lived microtubules along the anticlinal wall predict the patterns of lobe formation. In fields of lobing cells, anticlinal microtubules are not correlated with cell shape and are unstable at the time scales of cell expansion. Our analyses indicate that anticlinal microtubules have multiple functions in pavement cells and that lobe initiation is likely controlled by complex interactions among cell geometry, cell wall stress patterns, and transient microtubule networks that span the anticlinal and periclinal walls. © 2018 American Society of Plant Biologists. All Rights Reserved.

DP-THOT - a calculational tool for bundle-specific decay power based on actual irradiation history

International Nuclear Information System (INIS)

Johnston, S.; Morrison, C.A.; Albasha, H.; Arguner, D.

2005-01-01

. Information on the operating state of the core is calculated and recorded at regular intervals using the SORO fuel management code. To retrieve the complete history of an individual bundle requires tracking the bundle back from its current location, through all previously occupied locations in the core, to the fuelling operation at which the bundle first entered the core. Taking account of all intervening core states, including periods of shutdown or reduced reactor power, a histogram can then be constructed representing the entire power history of the bundle up to any subsequent point during its residence within the core. Existing capability within the SORO auxiliary suite of codes was built upon to facilitate the process of retrieving the complete irradiation history of a bundle specified in terms of its current location in the core. An interfacing routine was written to automate the process of obtaining input from the user, retrieving the bundle power history from SORO files, providing the history in the format needed for input to the decay power calculation module, executing the decay power program, and directing output back to the user. Information supplied by the user comprises identification of the reactor unit and bundles or channels which are of interest, the time and date of shutdown subsequent to which decay powers are to be calculated, as well as the associated decay time intervals. Where the decay power for complete channels is requested, the calculation is completed on a bundle by bundle basis, and then the resulting bundle decay powers are summed to yield the overall decay power for the channel. When a core scan is requested, the calculation is undertaken for every channel and bundle in the core. The tool has been extensively tested and results from its application are presented. (author)

One stage revision single-bundle anterior cruciate ligament reconstruction with impacted morselized bone graft following a failed double-bundle reconstruction

Directory of Open Access Journals (Sweden)

Ho Jong Ra

2017-01-01

Full Text Available Although double-bundle anterior cruciate ligament (ACL reconstruction has theoretical benefits such as more accurate reproduction of ACL anatomy, it is technically more demanding surgery. This report describes the case of a one stage revision single-bundle ACL reconstruction after primary double-bundle ACL reconstruction. A professional dancer had an ACL previously reconstructed with a double-bundle technique, but the femoral tunnels were malpositioned resulting in residual laxity and rotational instability. The previous femoral tunnel positions were vertical and widened. The previous vertical tunnels were filled with impacted bone graft and a revision single-bundle ACL reconstruction was performed via the new femoral tunnel with a 2 O'clock position between the previous two tunnels. After 10 months of postoperative rehabilitation, the patient returned to professional dancing with sound bony union and without any residual instability.

Bundling of elastic filaments induced by hydrodynamic interactions

Science.gov (United States)

Man, Yi; Page, William; Poole, Robert J.; Lauga, Eric

2017-12-01

Peritrichous bacteria swim in viscous fluids by rotating multiple helical flagellar filaments. As the bacterium swims forward, all its flagella rotate in synchrony behind the cell in a tight helical bundle. When the bacterium changes its direction, the flagellar filaments unbundle and randomly reorient the cell for a short period of time before returning to their bundled state and resuming swimming. This rapid bundling and unbundling is, at its heart, a mechanical process whereby hydrodynamic interactions balance with elasticity to determine the time-varying deformation of the filaments. Inspired by this biophysical problem, we present in this paper what is perhaps the simplest model of bundling whereby two or more straight elastic filaments immersed in a viscous fluid rotate about their centerline, inducing rotational flows which tend to bend the filaments around each other. We derive an integrodifferential equation governing the shape of the filaments resulting from mechanical balance in a viscous fluid at low Reynolds number. We show that such equation may be evaluated asymptotically analytically in the long-wavelength limit, leading to a local partial differential equation governed by a single dimensionless bundling number. A numerical study of the dynamics predicted by the model reveals the presence of two configuration instabilities with increasing bundling numbers: first to a crossing state where filaments touch at one point and then to a bundled state where filaments wrap along each other in a helical fashion. We also consider the case of multiple filaments and the unbundling dynamics. We next provide an intuitive physical model for the crossing instability and show that it may be used to predict analytically its threshold and adapted to address the transition to a bundling state. We then use a macroscale experimental implementation of the two-filament configuration in order to validate our theoretical predictions and obtain excellent agreement. This long

PDS4 Bundle Creation Governance Using BPMN

Science.gov (United States)

Radulescu, C.; Levoe, S. R.; Algermissen, S. S.; Rye, E. D.; Hardman, S. H.

2015-06-01

The AMMOS-PDS Pipeline Service (APPS) provides a Bundle Builder tool, which governs the process of creating, and ultimately generates, PDS4 bundles incrementally, as science products are being generated.

Reducing hospital-acquired pressure ulcers using bundle methodology in pediatric and neonatal patients receiving extracorporeal membrane oxygenation therapy: An integrative review and call to action.

Science.gov (United States)

Courtwright, Suzanne E; Mastro, Kari A; Preuster, Christa; Dardashti, Navid; McGill, Sandra; Madelon, Myrlene; Johnson, Donna

2017-10-01

This review focuses on identifying (1) evidence of the effectiveness of care bundle methodology to reduce hospital-acquired pressure ulcers (HAPUs) in pediatric and neonatal patients receiving extracorporeal membrane oxygenation (ECMO) therapy and (2) barriers to implementing HAPU care bundles in this at-risk population. An integrative review was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A search of the scientific literature was performed. Studies included were published between January 2011 and February 2016. A total of seven articles met inclusion criteria. Data were extracted from each published article and analyzed to identify common themes, specifically bundle methodology and barriers to implementing HAPU bundles, in this population. There is limited research on effectiveness of care bundle methodology in reducing HAPUs in children, and no research specific to its effectiveness in pediatric or neonatal ECMO patients. No research was identified studying barriers to implementation of HAPU care bundles in this population. Nurses are well poised to test innovative strategies to prevent HAPUs. Nurses should consider implementing and testing bundle methodology to reduce HAPU in this at-risk population, and conduct research to identify any barriers to implementing this strategy. There is literature to support the use of nurses as unit-based skin care champions to facilitate teamwork and reliable use of the bundle, both critical components to the success of bundle methodology. © 2017 Wiley Periodicals, Inc.

Enthalpy and void distributions in subchannels of PHWR fuel bundles

Energy Technology Data Exchange (ETDEWEB)

Park, J W; Choi, H; Rhee, B W [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

1999-12-31

Two different types of the CANDU fuel bundles have been modeled for the ASSERT-IV code subchannel analysis. From calculated values of mixture enthalpy and void fraction distribution in the fuel bundles, it is found that net buoyancy effect is pronounced in the central region of the DUPIC fuel bundle when compared with the standard CANDU fuel bundle. It is also found that the central region of the DUPIC fuel bundle can be cooled more efficiently than that of the standard fuel bundle. From the calculated mixture enthalpy distribution at the exit of the fuel channel, it is found that the mixture enthalpy and void fraction can be highest in the peripheral region of the DUPIC fuel bundle. On the other hand, the enthalpy and the void fraction were found to be highest in the central region of the standard CANDU fuel bundle at the exit of the fuel channel. This study shows that the subchannel analysis is very useful in assessing thermal behavior of the fuel bundle that could be used in CANDU reactors. 10 refs., 4 figs., 2 tabs. (Author)

Enthalpy and void distributions in subchannels of PHWR fuel bundles

Energy Technology Data Exchange (ETDEWEB)

Park, J. W.; Choi, H.; Rhee, B. W. [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

1998-12-31

Two different types of the CANDU fuel bundles have been modeled for the ASSERT-IV code subchannel analysis. From calculated values of mixture enthalpy and void fraction distribution in the fuel bundles, it is found that net buoyancy effect is pronounced in the central region of the DUPIC fuel bundle when compared with the standard CANDU fuel bundle. It is also found that the central region of the DUPIC fuel bundle can be cooled more efficiently than that of the standard fuel bundle. From the calculated mixture enthalpy distribution at the exit of the fuel channel, it is found that the mixture enthalpy and void fraction can be highest in the peripheral region of the DUPIC fuel bundle. On the other hand, the enthalpy and the void fraction were found to be highest in the central region of the standard CANDU fuel bundle at the exit of the fuel channel. This study shows that the subchannel analysis is very useful in assessing thermal behavior of the fuel bundle that could be used in CANDU reactors. 10 refs., 4 figs., 2 tabs. (Author)

Microtubule-Mediated Inositol Lipid Signaling Plays Critical Roles in Regulation of Blebbing.

Directory of Open Access Journals (Sweden)

Tatsuroh Sugiyama

Full Text Available Cells migrate by extending pseudopods such as lamellipodia and blebs. Although the signals leading to lamellipodia extension have been extensively investigated, those for bleb extension remain unclear. Here, we investigated signals for blebbing in Dictyostelium cells using a newly developed assay to induce blebbing. When cells were cut into two pieces with a microneedle, the anucleate fragments vigorously extended blebs. This assay enabled us to induce blebbing reproducibly, and analyses of knockout mutants and specific inhibitors identified candidate molecules that regulate blebbing. Blebs were also induced in anucleate fragments of leukocytes, indicating that this assay is generally applicable to animal cells. After cutting, microtubules in the anucleate fragments promptly depolymerized, followed by the extension of blebs. Furthermore, when intact cells were treated with a microtubule inhibitor, they frequently extended blebs. The depolymerization of microtubules induced the delocalization of inositol lipid phosphatidylinositol 3,4,5-trisphosphate from the cell membrane. PI3 kinase-null cells frequently extended blebs, whereas PTEN-null cells extended fewer blebs. From these observations, we propose a model in which microtubules play a critical role in bleb regulation via inositol lipid metabolism.

CANFLEX fuel bundle junction pressure drop

International Nuclear Information System (INIS)

Chung, H. J.; Chung, C. H.; Jun, J. S.; Hong, S. D.; Chang, S. K.; Kim, B. D.

1996-11-01

This report describes the junction pressure drop test results which are to used to determine the alignment angle between bundles to achieve the most probable fuel string pressure drop for randomly aligned bundles for use in the fuel string total pressure drop test. (author). 4 tabs., 17 figs

CANFLEX fuel bundle junction pressure drop

Energy Technology Data Exchange (ETDEWEB)

Chung, H. J.; Chung, C. H.; Jun, J. S.; Hong, S. D.; Chang, S. K.; Kim, B. D.

1996-11-01

This report describes the junction pressure drop test results which are to used to determine the alignment angle between bundles to achieve the most probable fuel string pressure drop for randomly aligned bundles for use in the fuel string total pressure drop test. (author). 4 tabs., 17 figs.

Imaging of Pericardiophrenic Bundles Using Multislice Spiral Computed Tomography for Phrenic Nerve Anatomy.

Science.gov (United States)

Wang, Yan-Jing; Liu, Lin; Zhang, Meng-Chao; Sun, Huan; Zeng, Hong; Yang, Ping

2016-08-01

Phrenic nerve injury and diaphragmatic stimulation are common complications following arrhythmia ablation and pacing therapies. Preoperative comprehension of phrenic nerve anatomy via non-invasive CT imaging may help to minimize the electrophysiological procedure-related complications. Coronary CT angiography data of 121 consecutive patients were collected. Imaging of left and right pericardiophrenic bundles was performed with volume rendering and multi-planar reformation techniques. The shortest spatial distances between phrenic nerves and key electrophysiology-related structures were determined. The frequencies of the shortest distances ≤5 mm, >5 mm and direct contact between phrenic nerves and adjacent structures were calculated. Left and right pericardiophrenic bundles were identified in 86.8% and 51.2% of the patients, respectively. The right phrenic nerve was phrenic nerve, phrenic nerve was phrenic nerve had a distance phrenic nerve showed a distance phrenic nerve anatomy, which might facilitate avoidance of the phrenic nerve-related complications in interventional electrophysiology. © 2016 Wiley Periodicals, Inc.

Microtubule-Targeting Agents Enter the Central Nervous System (CNS): Double-edged Swords for Treating CNS Injury and Disease.

Science.gov (United States)

Hur, Eun-Mi; Lee, Byoung Dae

2014-12-01

Microtubules have been among the most successful targets in anticancer therapy and a large number of microtubule-targeting agents (MTAs) are in various stages of clinical development for the treatment of several malignancies. Given that injury and diseases in the central nervous system (CNS) are accompanied by acute or chronic disruption of the structural integrity of neurons and that microtubules provide structural support for the nervous system at cellular and intracellular levels, microtubules are emerging as potential therapeutic targets for treating CNS disorders. It has been postulated that exogenous application of MTAs might prevent the breakdown or degradation of microtubules after injury or during neurodegeneration, which will thereby aid in preserving the structural integrity and function of the nervous system. Here we review recent evidence that supports this notion and also discuss potential risks of targeting microtubules as a therapy for treating nerve injury and neurodegenerative diseases.

Microtubule-Targeting Agents Enter the Central Nervous System (CNS: Double-edged Swords for Treating CNS Injury and Disease

Directory of Open Access Journals (Sweden)

Eun-Mi Hur

2014-12-01

Full Text Available Microtubules have been among the most successful targets in anticancer therapy and a large number of microtubule-targeting agents (MTAs are in various stages of clinical development for the treatment of several malignancies. Given that injury and diseases in the central nervous system (CNS are accompanied by acute or chronic disruption of the structural integrity of neurons and that microtubules provide structural support for the nervous system at cellular and intracellular levels, microtubules are emerging as potential therapeutic targets for treating CNS disorders. It has been postulated that exogenous application of MTAs might prevent the breakdown or degradation of microtubules after injury or during neurodegeneration, which will thereby aid in preserving the structural integrity and function of the nervous system. Here we review recent evidence that supports this notion and also discuss potential risks of targeting microtubules as a therapy for treating nerve injury and neurodegenerative diseases.

Synthesis and biological evaluation of structurally simplified noscapine analogues as microtubule binding agents

Czech Academy of Sciences Publication Activity Database

Ghaly, P.E.; Churchill, C.D.M.; Abou El-Magd, R.M.; Hájková, Zuzana; Dráber, Pavel; West, F.G.; Tuszyński, J.A.

2017-01-01

Roč. 95, č. 6 (2017), s. 649-655 ISSN 0008-4042 R&D Projects: GA ČR GA15-22194S Institutional support: RVO:68378050 Keywords : noscapine * microtubule * tubulin * cytotoxicity * microtubule dynamics * docking Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 1.080, year: 2016

Lateral motion and bending of microtubules studied with a new single-filament tracking routine in living cells.

Science.gov (United States)

Pallavicini, Carla; Levi, Valeria; Wetzler, Diana E; Angiolini, Juan F; Benseñor, Lorena; Despósito, Marcelo A; Bruno, Luciana

2014-06-17

The cytoskeleton is involved in numerous cellular processes such as migration, division, and contraction and provides the tracks for transport driven by molecular motors. Therefore, it is very important to quantify the mechanical behavior of the cytoskeletal filaments to get a better insight into cell mechanics and organization. It has been demonstrated that relevant mechanical properties of microtubules can be extracted from the analysis of their motion and shape fluctuations. However, tracking individual filaments in living cells is extremely complex due, for example, to the high and heterogeneous background. We introduce a believed new tracking algorithm that allows recovering the coordinates of fluorescent microtubules with ∼9 nm precision in in vitro conditions. To illustrate potential applications of this algorithm, we studied the curvature distributions of fluorescent microtubules in living cells. By performing a Fourier analysis of the microtubule shapes, we found that the curvatures followed a thermal-like distribution as previously reported with an effective persistence length of ∼20 μm, a value significantly smaller than that measured in vitro. We also verified that the microtubule-associated protein XTP or the depolymerization of the actin network do not affect this value; however, the disruption of intermediate filaments decreased the persistence length. Also, we recovered trajectories of microtubule segments in actin or intermediate filament-depleted cells, and observed a significant increase of their motion with respect to untreated cells showing that these filaments contribute to the overall organization of the microtubule network. Moreover, the analysis of trajectories of microtubule segments in untreated cells showed that these filaments presented a slower but more directional motion in the cortex with respect to the perinuclear region, and suggests that the tracking routine would allow mapping the microtubule dynamical organization in cells

Molecular architecture of axonemal microtubule doublets revealedby cryo-electron tomography

Energy Technology Data Exchange (ETDEWEB)

Sui, Haixin; Downing, Kenneth H.

2006-05-22

The axoneme, which forms the core of eukaryotic flagella and cilia, is one of the largest macromolecular machines with a structure that is largely conserved from protists to mammals. Microtubule doublets are structural components of axonemes containing a number of proteins besides tubulin, and are usually found in arrays of nine doublets arranged around two singlet microtubules. Coordinated sliding of adjacent doublets, which involves a host of other proteins in the axoneme, produces periodic beating movements of the axoneme. We have obtained a 3D density map of intact microtubule doublets using cryo-electron tomography and image averaging. Our map, with a resolution of about 3 nm, provides insights into locations of particular proteins within the doublets and the structural features of the doublets that define their mechanical properties. We identify likely candidates for several of these non-tubulin components of the doublets. This work offers novel insight on how tubulin protofilaments and accessory proteins attach together to form the doublets and provides a structural basis for understanding doublet function in axonemes.

Restriction of Preferences to the Set of Consumption Bundles, In a Model with Production and Consumption Bundles

NARCIS (Netherlands)

Schalk, S.

1999-01-01

In contrast to the neo-classical theory of Arrow and Debreu, a model of a private ownership economy is presented, in which production and consumption bundles are treated separately. Each of the two types of bundles is assumed to establish a con- vex cone. Production technologies can convert

An agent-based model contrasts opposite effects of dynamic and stable microtubules on cleavage furrow positioning.

Science.gov (United States)

Odell, Garrett M; Foe, Victoria E

2008-11-03

From experiments by Foe and von Dassow (Foe, V.E., and G. von Dassow. 2008. J. Cell Biol. 183:457-470) and others, we infer a molecular mechanism for positioning the cleavage furrow during cytokinesis. Computer simulations reveal how this mechanism depends on quantitative motor-behavior details and explore how robustly this mechanism succeeds across a range of cell sizes. The mechanism involves the MKLP1 (kinesin-6) component of centralspindlin binding to and walking along microtubules to stimulate cortical contractility where the centralspindlin complex concentrates. The majority of astral microtubules are dynamically unstable. They bind most MKLP1 and suppress cortical Rho/myosin II activation because the tips of unstable microtubules usually depolymerize before MKLP1s reach the cortex. A subset of astral microtubules stabilizes during anaphase, becoming effective rails along which MKLP1 can actually reach the cortex. Because stabilized microtubules aim statistically at the equatorial spindle midplane, that is where centralspindlin accumulates to stimulate furrow formation.

GPU Parallel Bundle Block Adjustment

Directory of Open Access Journals (Sweden)

ZHENG Maoteng

2017-09-01

Full Text Available To deal with massive data in photogrammetry, we introduce the GPU parallel computing technology. The preconditioned conjugate gradient and inexact Newton method are also applied to decrease the iteration times while solving the normal equation. A brand new workflow of bundle adjustment is developed to utilize GPU parallel computing technology. Our method can avoid the storage and inversion of the big normal matrix, and compute the normal matrix in real time. The proposed method can not only largely decrease the memory requirement of normal matrix, but also largely improve the efficiency of bundle adjustment. It also achieves the same accuracy as the conventional method. Preliminary experiment results show that the bundle adjustment of a dataset with about 4500 images and 9 million image points can be done in only 1.5 minutes while achieving sub-pixel accuracy.

Flow in rod bundles

International Nuclear Information System (INIS)

Hazi, G.; Mayer, G.

2005-01-01

For power upgrading VVER-440 reactors we need to know exactly how the temperature measured by the thermocouples is related to the average outlet temperature of the fuel assemblies. Accordingly, detailed knowledge on mixing process in the rod bundles and in the fuel assembly head have great importance. Here we study the hydrodynamics of rod bundles based on the results of direct numerical and large eddy simulation of flows in subchannels. It is shown that secondary flow and flow pulsation phenomena can be observed using both methodologies. Some consequences of these observations are briefly discussed. (author)

Bundling harvester; Nippukorjausharvesteri

Energy Technology Data Exchange (ETDEWEB)

Koponen, K [Eko-Log Oy, Kuopio (Finland)

1997-12-31

The staring point of the project was to design and construct, by taking the silvicultural point of view into account, a harvesting and processing system especially for energy-wood, containing manually driven bundling harvester, automatizing of the harvester, and automatized loading. The equipment forms an ideal method for entrepreneur`s-line harvesting. The target is to apply the system also for owner`s-line harvesting. The profitability of the system promotes the utilization of the system in both cases. The objectives of the project were: to construct a test equipment and prototypes for all the project stages, to carry out terrain and strain tests in order to examine the usability and durability, as well as the capacity of the machine, to test the applicability of the Eko-Log system in simultaneous harvesting of energy and pulp woods, and to start the marketing and manufacturing of the products. The basic problems of the construction of the bundling harvester have been solved using terrain-tests. The prototype machine has been shown to be operable. Loading of the bundles to form sufficiently economically transportable loads has been studied, and simultaneously, the branch-biomass has been tried to be utilized without loosing the profitability of transportation. The results have been promising, and will promote the profitable utilization of wood-energy

Bundling harvester; Nippukorjausharvesteri

Energy Technology Data Exchange (ETDEWEB)

Koponen, K. [Eko-Log Oy, Kuopio (Finland)

1996-12-31

The staring point of the project was to design and construct, by taking the silvicultural point of view into account, a harvesting and processing system especially for energy-wood, containing manually driven bundling harvester, automatizing of the harvester, and automatized loading. The equipment forms an ideal method for entrepreneur`s-line harvesting. The target is to apply the system also for owner`s-line harvesting. The profitability of the system promotes the utilization of the system in both cases. The objectives of the project were: to construct a test equipment and prototypes for all the project stages, to carry out terrain and strain tests in order to examine the usability and durability, as well as the capacity of the machine, to test the applicability of the Eko-Log system in simultaneous harvesting of energy and pulp woods, and to start the marketing and manufacturing of the products. The basic problems of the construction of the bundling harvester have been solved using terrain-tests. The prototype machine has been shown to be operable. Loading of the bundles to form sufficiently economically transportable loads has been studied, and simultaneously, the branch-biomass has been tried to be utilized without loosing the profitability of transportation. The results have been promising, and will promote the profitable utilization of wood-energy

A Tannakian approach to dimensional reduction of principal bundles

Science.gov (United States)

Álvarez-Cónsul, Luis; Biswas, Indranil; García-Prada, Oscar

2017-08-01

Let P be a parabolic subgroup of a connected simply connected complex semisimple Lie group G. Given a compact Kähler manifold X, the dimensional reduction of G-equivariant holomorphic vector bundles over X × G / P was carried out in Álvarez-Cónsul and García-Prada (2003). This raises the question of dimensional reduction of holomorphic principal bundles over X × G / P. The method of Álvarez-Cónsul and García-Prada (2003) is special to vector bundles; it does not generalize to principal bundles. In this paper, we adapt to equivariant principal bundles the Tannakian approach of Nori, to describe the dimensional reduction of G-equivariant principal bundles over X × G / P, and to establish a Hitchin-Kobayashi type correspondence. In order to be able to apply the Tannakian theory, we need to assume that X is a complex projective manifold.

Coupling of kinesin ATP turnover to translocation and microtubule regulation: one engine, many machines.

Science.gov (United States)

Friel, Claire T; Howard, Jonathon

2012-12-01

The cycle of ATP turnover is integral to the action of motor proteins. Here we discuss how variation in this cycle leads to variation of function observed amongst members of the kinesin superfamily of microtubule associated motor proteins. Variation in the ATP turnover cycle among superfamily members can tune the characteristic kinesin motor to one of the range of microtubule-based functions performed by kinesins. The speed at which ATP is hydrolysed affects the speed of translocation. The ratio of rate constants of ATP turnover in relation to association and dissociation from the microtubule influence the processivity of translocation. Variation in the rate-limiting step of the cycle can reverse the way in which the motor domain interacts with the microtubule producing non-motile kinesins. Because the ATP turnover cycle is not fully understood for the majority of kinesins, much work remains to show how the kinesin engine functions in such a wide variety of molecular machines.

GIT1 enhances neurite outgrowth by stimulating microtubule assembly

Directory of Open Access Journals (Sweden)

Yi-sheng Li

2016-01-01

Full Text Available GIT1, a G-protein-coupled receptor kinase interacting protein, has been reported to be involved in neurite outgrowth. However, the neurobiological functions of the protein remain unclear. In this study, we found that GIT1 was highly expressed in the nervous system, and its expression was maintained throughout all stages of neuritogenesis in the brain. In primary cultured mouse hippocampal neurons from GIT1 knockout mice, there was a significant reduction in total neurite length per neuron, as well as in the average length of axon-like structures, which could not be prevented by nerve growth factor treatment. Overexpression of GIT1 significantly promoted axon growth and fully rescued the axon outgrowth defect in the primary hippocampal neuron cultures from GIT1 knockout mice. The GIT1 N terminal region, including the ADP ribosylation factor-GTPase activating protein domain, the ankyrin domains and the Spa2 homology domain, were sufficient to enhance axonal extension. Importantly, GIT1 bound to many tubulin proteins and microtubule-associated proteins, and it accelerated microtubule assembly in vitro. Collectively, our findings suggest that GIT1 promotes neurite outgrowth, at least partially by stimulating microtubule assembly. This study provides new insight into the cellular and molecular pathogenesis of GIT1-associated neurological diseases.

Restriction Theorem for Principal bundles in Arbitrary Characteristic

DEFF Research Database (Denmark)

Gurjar, Sudarshan

2015-01-01

The aim of this paper is to prove two basic restriction theorem for principal bundles on smooth projective varieties in arbitrary characteristic generalizing the analogues theorems of Mehta-Ramanathan for vector bundles. More precisely, let G be a reductive algebraic group over an algebraically...... closed field k and let X be a smooth, projective variety over k together with a very ample line bundle O(1). The main result of the paper is that if E is a semistable (resp. stable) principal G-bundle on X w.r.t O(1), then the restriction of E to a general, high multi-degree, complete-intersection curve...

Wave equations on a de Sitter fiber bundle. [Semiclassical wave function, bundle space, L-S coupling

Energy Technology Data Exchange (ETDEWEB)

Drechsler, W [Max-Planck-Institut fuer Physik und Astrophysik, Muenchen (F.R. Germany)

1975-01-01

A gauge theory of strong interaction is developed based on fields defined on a fiber bundle. The structural group of the bundle is taken to be the Lsub(4,1) de Sitter group. An internal variable xi, varying in the fiber over a space-time point x, is introduced as a means to describe - with the help of a semiclassical wave function psi(x,xi) defined on the bundle space - the internal structure of extended hadrons in a framework using differential geometric techniques. Three basic nonlinear wave equations for psi(x,xi) are established which are of integro-differential type. The nonlinear coupling terms in these de Sitter gauge invariant equations represent physically a generalized spin orbit coupling or a generalized spin coupling for the motion taking place in the fiber. The motivation for using a bigger space for the definition of hadronic matter wave functions as well as the implications of this geometric approach to strong interaction physics is discussed in detail, in particular with respect to the problem of hadronic constituents. The proposed fiber bundle formalism allows a dynamical description of extended structures for hadrons without implying the necessity of introducing any constituents.

Relativistic rotators: a quantum mechanical de Sitter bundle

International Nuclear Information System (INIS)

Boehm, A.

1976-02-01

If de Sitter fiber bundle over space time is the classical picture of hadrons then for a quantum mechanical description one has to generalize the concept of a principal fiber bundle to a bundle that contains the representation of the group of motion. This idea is related to the relativistic rotator model, and the radius of the de Sitter fiber is determined from the experimental hadron spectrum

Bundling Actin Filaments From Membranes: Some Novel Players

Directory of Open Access Journals (Sweden)

Clément eThomas

2012-08-01

Full Text Available Progress in live-cell imaging of the cytoskeleton has significantly extended our knowledge about the organization and dynamics of actin filaments near the plasma membrane of plant cells. Noticeably, two populations of filamentous structures can be distinguished. On the one hand, fine actin filaments which exhibit an extremely dynamic behavior basically characterized by fast polymerization and prolific severing events, a process referred to as actin stochastic dynamics. On the other hand, thick actin bundles which are composed of several filaments and which are comparatively more stable although they constantly remodel as well. There is evidence that the actin cytoskeleton plays critical roles in trafficking and signaling at both the cell cortex and organelle periphery but the exact contribution of actin bundles remains unclear. A common view is that actin bundles provide the long-distance tracks used by myosin motors to deliver their cargo to growing regions and accordingly play a particularly important role in cell polarization. However, several studies support that actin bundles are more than simple passive highways and display multiple and dynamic roles in the regulation of many processes, such as cell elongation, polar auxin transport, stomatal and chloroplast movement, and defense against pathogens. The list of identified plant actin-bundling proteins is ever expanding, supporting that plant cells shape structurally and functionally different actin bundles. Here I review the most recently characterized actin-bundling proteins, with a particular focus on those potentially relevant to membrane trafficking and/or signaling.

Adoption of Dynamic Product Information: An Empirical Investigation of Supporting Purchase Decisions on Product Bundles

OpenAIRE

Maass, Wolfgang; Kowatsch, Tobias

2008-01-01

Up until now, brick-and-mortar stores provide consumers with static product information in the form of printed product labels. This kind of product information does neither adapt to consumer needs nor facilitates new business models (e.g. consumer experience or ad hoc product bundling by products itself). By contrast, dynamic product information provided by mobile recommendation agents (MRA) may leverage these limitations. In this article we formulate a Simplified Consumer Choice (SCC) model ...

NIF laser bundle review. Final report

International Nuclear Information System (INIS)

Tietbohl, G.L.; Larson, D.W.; Erlandson, A.C.

1995-01-01

We performed additional bundle review effort subsequent to the completion of the preliminary report and are revising our original recommendations. We now recommend that the NIF baseline laser bundle size be changed to the 4x2 bundle configuration. There are several 4x2 bundle configurations that could be constructed at a cost similar to that of the baseline 4x12 (from $11M more to about $11M less than the baseline; unescalated, no contingency) and provide significant system improvements. We recommend that the building cost estimates (particularly for the in-line building options) be verified by an architect/engineer (A/E) firm knowledgeable about building design. If our cost estimates of the in-line building are accurate and therefore result in a change from the baseline U-shaped building layout, the acceptability of the in-line configuration must be reviewed from an operations viewpoint. We recommend that installation, operation, and maintenance of all laser components be reviewed to better determine the necessity of aisles, which add to the building cost significantly. The need for beam expansion must also be determined since it affects the type of bundle packing that can be used and increases the minimum laser bay width. The U-turn laser architecture (if proven viable) offers a reduction in building costs since this laser design is shorter than the baseline switched design and requires a shorter laser bay

Image-Based Edge Bundles : Simplified Visualization of Large Graphs

NARCIS (Netherlands)

Telea, A.; Ersoy, O.

2010-01-01

We present a new approach aimed at understanding the structure of connections in edge-bundling layouts. We combine the advantages of edge bundles with a bundle-centric simplified visual representation of a graph's structure. For this, we first compute a hierarchical edge clustering of a given graph

Finding the Cell Center by a Balance of Dynein and Myosin Pulling and Microtubule Pushing: A Computational Study

Science.gov (United States)

Zhu, Jie; Burakov, Anton; Rodionov, Vladimir

2010-01-01

The centrosome position in many types of interphase cells is actively maintained in the cell center. Our previous work indicated that the centrosome is kept at the center by pulling force generated by dynein and actin flow produced by myosin contraction and that an unidentified factor that depends on microtubule dynamics destabilizes position of the centrosome. Here, we use modeling to simulate the centrosome positioning based on the idea that the balance of three forces—dyneins pulling along microtubule length, myosin-powered centripetal drag, and microtubules pushing on organelles—is responsible for the centrosome displacement. By comparing numerical predictions with centrosome behavior in wild-type and perturbed interphase cells, we rule out several plausible hypotheses about the nature of the microtubule-based force. We conclude that strong dynein- and weaker myosin-generated forces pull the microtubules inward competing with microtubule plus-ends pushing the microtubule aster outward and that the balance of these forces positions the centrosome at the cell center. The model also predicts that kinesin action could be another outward-pushing force. Simulations demonstrate that the force-balance centering mechanism is robust yet versatile. We use the experimental observations to reverse engineer the characteristic forces and centrosome mobility. PMID:20980619

Fiber bundle geometry and space-time structure

International Nuclear Information System (INIS)

Nascimento, J.C.

1977-01-01

Within the framework of the geometric formulation of Gauge theories in fiber bundles, the general relation between the bundle connection (Gauge field) and the geometry of the base space is obtained. A possible Gauge theory for gravitation is presented [pt

Three-dimensional fine structure of the organization of microtubules in neurite varicosities by ultra-high voltage electron microscope tomography.

Science.gov (United States)

Nishida, Tomoki; Yoshimura, Ryoichi; Endo, Yasuhisa

2017-09-01

Neurite varicosities are highly specialized compartments that are involved in neurotransmitter/ neuromodulator release and provide a physiological platform for neural functions. However, it remains unclear how microtubule organization contributes to the form of varicosity. Here, we examine the three-dimensional structure of microtubules in varicosities of a differentiated PC12 neural cell line using ultra-high voltage electron microscope tomography. Three-dimensional imaging showed that a part of the varicosities contained an accumulation of organelles that were separated from parallel microtubule arrays. Further detailed analysis using serial sections and whole-mount tomography revealed microtubules running in a spindle shape of swelling in some other types of varicosities. These electron tomographic results showed that the structural diversity and heterogeneity of microtubule organization supported the form of varicosities, suggesting that a different distribution pattern of microtubules in varicosities is crucial to the regulation of varicosities development.

Triviality and Split of Vector Bundles on Rationally Connected Varieties

OpenAIRE

Pan, Xuanyu

2013-01-01

In this paper, we give a simple proof of a triviality criterion due to I.Biswas and J.Pedro and P.Dos Santos. We also prove a vector bundle on a homogenous space is trivial if and only if the restrictions of the vector bundle to Schubert lines are trivial. Using this result and Chern classes of vector bundles, we give a general criterion of a uniform vector bundle on a homogenous space to be splitting. As an application, we prove a uniform vector bundle on classical Grassmannians and quadrics...

CANDU fuel bundle deformation modelling with COMSOL multiphysics

International Nuclear Information System (INIS)

Bell, J.S.; Lewis, B.J.

2012-01-01

Highlights: ► The deformation behaviour of a CANDU fuel bundle was modelled. ► The model has been developed on a commercial finite-element platform. ► Pellet/sheath interaction and end-plate restraint effects were considered. ► The model was benchmarked against the BOW code and a variable-load experiment. - Abstract: A model to describe deformation behaviour of a CANDU 37-element bundle has been developed under the COMSOL Multiphysics finite-element platform. Beam elements were applied to the fuel elements (composed of fuel sheaths and pellets) and endplates in order to calculate the bowing behaviour of the fuel elements. This model is important to help assess bundle-deformation phenomena, which may lead to more restrictive coolant flow through the sub-channels of the horizontally oriented bundle. The bundle model was compared to the BOW code for the occurrence of a dry-out patch, and benchmarked against an out-reactor experiment with a variable load on an outer fuel element.

Wire-wrap bundle compression-characteristics study. Phase I

International Nuclear Information System (INIS)

Chertock, A.J.

1974-06-01

An analytical computer comparison was made of the compression characteristics of proposed wire-wrap bundles. The study included analysis of 7- and 37-rod straight-start bundles (base configuration), and softened 37-rod configurations. The softened configurations analyzed were: straight-start with distributed wireless fuel rods, and the staggered wire-wrap start angles of 0 0 -30 0 -60 0 and 0 0 -45 0 -90 0 . The compression of the bundle simulates the bundle-to-channel interference at end-of-life conditions at which high differential swelling between the channel and bundle has been predicted. The computer results do not include the so-called dispersion effects. The effects of other variables such as pitch length, creep, axial variations in swelling, and degree of swelling were not studied. These analytic studies give an indication of trends only. No credence should be given to specific quantitative load or deflection results quoted in this report

Erucin, the major isothiocyanate in arugula (Eruca sativa, inhibits proliferation of MCF7 tumor cells by suppressing microtubule dynamics.

Directory of Open Access Journals (Sweden)

Olga Azarenko

Full Text Available Consumption of cruciferous vegetables is associated with reduced risk of various types of cancer. Isothiocyanates including sulforaphane and erucin are believed to be responsible for this activity. Erucin [1-isothiocyanato-4-(methylthiobutane], which is metabolically and structurally related to sulforaphane, is present in large quantities in arugula (Eruca sativa, Mill., kohlrabi and Chinese cabbage. However, its cancer preventive mechanisms remain poorly understood. We found that erucin inhibits proliferation of MCF7 breast cancer cells (IC50 = 28 µM in parallel with cell cycle arrest at mitosis (IC50 = 13 µM and apoptosis, by a mechanism consistent with impairment of microtubule dynamics. Concentrations of 5-15 µM erucin suppressed the dynamic instability of microtubules during interphase in the cells. Most dynamic instability parameters were inhibited, including the rates and extents of growing and shortening, the switching frequencies between growing and shortening, and the overall dynamicity. Much higher erucin concentrations were required to reduce the microtubule polymer mass. In addition, erucin suppressed dynamic instability of microtubules reassembled from purified tubulin in similar fashion. The effects of erucin on microtubule dynamics, like those of sulforaphane, are similar qualitatively to those of much more powerful clinically-used microtubule-targeting anticancer drugs, including taxanes and the vinca alkaloids. The results suggest that suppression of microtubule dynamics by erucin and the resulting impairment of critically important microtubule-dependent cell functions such as mitosis, cell migration and microtubule-based transport may be important in its cancer preventive activities.

Right bundle branch block

DEFF Research Database (Denmark)

Bussink, Barbara E; Holst, Anders Gaarsdal; Jespersen, Lasse

2013-01-01

AimsTo determine the prevalence, predictors of newly acquired, and the prognostic value of right bundle branch block (RBBB) and incomplete RBBB (IRBBB) on a resting 12-lead electrocardiogram in men and women from the general population.Methods and resultsWe followed 18 441 participants included...... in the Copenhagen City Heart Study examined in 1976-2003 free from previous myocardial infarction (MI), chronic heart failure, and left bundle branch block through registry linkage until 2009 for all-cause mortality and cardiovascular outcomes. The prevalence of RBBB/IRBBB was higher in men (1.4%/4.7% in men vs. 0.......5%/2.3% in women, P block was associated with significantly...

Design concept and testing of an in-bundle gamma densitometer for subchannel void fraction measurements in the THTF electrically heated rod bundle

International Nuclear Information System (INIS)

Felde, D.K.

1982-04-01

A design concept is presented for an in-bundle gamma densitometer system for measurement of subchannel average fluid density and void fraction in rod or tube bundles. This report describes (1) the application of the design concept to the Thermal-Hydraulic Test Facility (THTF) electrically heated rod bundle; and (2) results from tests conducted in the THTF

Topological T-duality for torus bundles with monodromy

Science.gov (United States)

Baraglia, David

2015-05-01

We give a simplified definition of topological T-duality that applies to arbitrary torus bundles. The new definition does not involve Chern classes or spectral sequences, only gerbes and morphisms between them. All the familiar topological conditions for T-duals are shown to follow. We determine necessary and sufficient conditions for existence of a T-dual in the case of affine torus bundles. This is general enough to include all principal torus bundles as well as torus bundles with arbitrary monodromy representations. We show that isomorphisms in twisted cohomology, twisted K-theory and of Courant algebroids persist in this general setting. We also give an example where twisted K-theory groups can be computed by iterating T-duality.

TCS1, a Microtubule-Binding Protein, Interacts with KCBP/ZWICHEL to Regulate Trichome Cell Shape in Arabidopsis thaliana.

Directory of Open Access Journals (Sweden)

Liangliang Chen

2016-10-01

Full Text Available How cell shape is controlled is a fundamental question in developmental biology, but the genetic and molecular mechanisms that determine cell shape are largely unknown. Arabidopsis trichomes have been used as a good model system to investigate cell shape at the single-cell level. Here we describe the trichome cell shape 1 (tcs1 mutants with the reduced trichome branch number in Arabidopsis. TCS1 encodes a coiled-coil domain-containing protein. Pharmacological analyses and observations of microtubule dynamics show that TCS1 influences the stability of microtubules. Biochemical analyses and live-cell imaging indicate that TCS1 binds to microtubules and promotes the assembly of microtubules. Further results reveal that TCS1 physically associates with KCBP/ZWICHEL, a microtubule motor involved in the regulation of trichome branch number. Genetic analyses indicate that kcbp/zwi is epistatic to tcs1 with respect to trichome branch number. Thus, our findings define a novel genetic and molecular mechanism by which TCS1 interacts with KCBP to regulate trichome cell shape by influencing the stability of microtubules.

Identification and characterization of SSE15206, a microtubule depolymerizing agent that overcomes multidrug resistance

KAUST Repository

Manzoor, Safia

2018-02-13

Microtubules are highly dynamic structures that form spindle fibres during mitosis and are one of the most validated cancer targets. The success of drugs targeting microtubules, however, is often limited by the development of multidrug resistance. Here we describe the discovery and characterization of SSE15206, a pyrazolinethioamide derivative [3-phenyl-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide] that has potent antiproliferative activities in cancer cell lines of different origins and overcomes resistance to microtubule-targeting agents. Treatment of cells with SSE15206 causes aberrant mitosis resulting in G2/M arrest due to incomplete spindle formation, a phenotype often associated with drugs that interfere with microtubule dynamics. SSE15206 inhibits microtubule polymerization both in biochemical and cellular assays by binding to colchicine site in tubulin as shown by docking and competition studies. Prolonged treatment of cells with the compound results in apoptotic cell death [increased Poly (ADP-ribose) polymerase cleavage and Annexin V/PI staining] accompanied by p53 induction. More importantly, we demonstrate that SSE15206 is able to overcome resistance to chemotherapeutic drugs in different cancer cell lines including multidrug-resistant KB-V1 and A2780-Pac-Res cell lines overexpressing MDR-1, making it a promising hit for the lead optimization studies to target multidrug resistance.

Bundle duct interaction studies for fuel assemblies

International Nuclear Information System (INIS)

Hsia, H.T.S.; Kaplan, S.

1981-06-01

It is known that the wire-wrapped rods and duct in an LMFBR are undergoing a gradual structural distortion from the initially uniform geometry under the combined effects of thermal expansion and irradiation induced swelling and creep. These deformations have a significant effect on flow characteristics, thus causing changes in thermal behavior such as cladding temperature and temperature distribution within a bundle. The temperature distribution may further enhance or retard irradiation induced deformation of the bundle. This report summarizes the results of the continuing effort in investigating the bundle-duct interaction, focusing on the need for the large development plant

Reassessing the Roles of PIN Proteins and Anticlinal Microtubules during Pavement Cell Morphogenesis1[OPEN

Science.gov (United States)

Sawchuk, Megan G.; Scarpella, Enrico

2018-01-01

The leaf epidermis is a biomechanical shell that influences the size and shape of the organ. Its morphogenesis is a multiscale process in which nanometer-scale cytoskeletal protein complexes, individual cells, and groups of cells pattern growth and define macroscopic leaf traits. Interdigitated growth of neighboring cells is an evolutionarily conserved developmental strategy. Understanding how signaling pathways and cytoskeletal proteins pattern cell walls during this form of tissue morphogenesis is an important research challenge. The cellular and molecular control of a lobed cell morphology is currently thought to involve PIN-FORMED (PIN)-type plasma membrane efflux carriers that generate subcellular auxin gradients. Auxin gradients were proposed to function across cell boundaries to encode stable offset patterns of cortical microtubules and actin filaments between adjacent cells. Many models suggest that long-lived microtubules along the anticlinal cell wall generate local cell wall heterogeneities that restrict local growth and specify the timing and location of lobe formation. Here, we used Arabidopsis (Arabidopsis thaliana) reverse genetics and multivariate long-term time-lapse imaging to test current cell shape control models. We found that neither PIN proteins nor long-lived microtubules along the anticlinal wall predict the patterns of lobe formation. In fields of lobing cells, anticlinal microtubules are not correlated with cell shape and are unstable at the time scales of cell expansion. Our analyses indicate that anticlinal microtubules have multiple functions in pavement cells and that lobe initiation is likely controlled by complex interactions among cell geometry, cell wall stress patterns, and transient microtubule networks that span the anticlinal and periclinal walls. PMID:29192026

Microtubule dynamics of the centrosome-like polar organizers from the basal land plant Marchantia polymorpha.

Science.gov (United States)

Buschmann, Henrik; Holtmannspötter, Michael; Borchers, Agnes; O'Donoghue, Martin-Timothy; Zachgo, Sabine

2016-02-01

The liverwort Marchantia employs both modern and ancestral devices during cell division: it forms preprophase bands and in addition it shows centrosome-like polar organizers. We investigated whether polar organizers and preprophase bands cooperate to set up the division plane. To this end, two novel green fluorescent protein-based microtubule markers for dividing cells of Marchantia were developed. Cells of the apical notch formed polar organizers first and subsequently assembled preprophase bands. Polar organizers were formed de novo from multiple mobile microtubule foci localizing to the nuclear envelope. The foci then became concentrated by bipolar aggregation. We determined the comet production rate of polar organizers and show that microtubule plus ends of astral microtubules polymerize faster than those found on cortical microtubules. Importantly, it was observed that conditions increasing polar organizer numbers interfere with preprophase band formation. The data show that polar organizers have much in common with centrosomes, but that they also have specialized features. The results suggest that polar organizers contribute to preprophase band formation and in this way are involved in controlling the division plane. Our analyses of the basal land plant Marchantia shed new light on the evolution of plant cell division. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Cationic membranes complexed with oppositely charged microtubules: hierarchical self-assembly leading to bio-nanotubes

International Nuclear Information System (INIS)

Raviv, Uri; Needleman, Daniel J; Safinya, Cyrus R

2006-01-01

The self-assembly of microtubules and charged membranes has been studied, using x-ray diffraction and electron microscopy. Polyelectrolyte lipid complexes usually form structures templated by the lipid phase, when the polyelectrolyte curvature is much larger than the membrane spontaneous curvature. When the polyelectrolyte curvature approaches the membrane spontaneous curvature, as in microtubules, two types of new structures emerge. Depending on the conditions, vesicles either adsorb onto the microtubule, forming a 'beads on a rod' structure, or coat the microtubule, which now forms the template. Tubulin oligomers then coat the external lipid layer, forming a lipid protein nanotube. The tubulin oligomer coverage at the external layer is determined by the membrane charge density. The energy barrier between the beads on a rod and the lipid-protein nanotube states depends on the membrane bending rigidity and membrane charge density. By controlling the lipid/tubulin stoichiometry we can switch between lipid-protein nanotubes with open ends to lipid-protein nanotubes with closed end with lipid cups. This forms the basis for controlled drug encapsulation and release

Experimental investigation of the coolability of blocked hexagonal bundles

Energy Technology Data Exchange (ETDEWEB)

Hózer, Zoltán, E-mail: zoltan.hozer@energia.mta.hu; Nagy, Imre; Kunstár, Mihály; Szabó, Péter; Vér, Nóra; Farkas, Róbert; Trosztel, István; Vimi, András

2017-06-15

Highlights: • Experiments were performed with electrically heated hexagonal fuel bundles. • Coolability of ballooned VVER-440 type bundle was confirmed up to high blockage rate. • Pellet relocation effect causes delay in the cool-down of the bundle. • The bypass line does not prevent the reflood of ballooned fuel rods. - Abstract: The CODEX-COOL experimental series was carried out in order to evaluate the effect of ballooning and pellet relocation in hexagonal bundles on the coolability of fuel rods after a LOCA event. The effects of blockage geometry, coolant flowrate, initial temperature and axial profile were investigated. The experimental results confirmed that a VVER bundle up to 80% blockage rate remains coolable after a LOCA event under design basis conditions. The ballooned section creates some obstacles for the cooling water during reflood of the bundle, but this effect causes only a short delay in the cooling down of the hot fuel rods. The accumulation of fuel pellet debris in the ballooned volume results in a local power peak, which leads to further slowing down of quench front.

Katanin spiral and ring structures shed light on power stroke for microtubule severing

Energy Technology Data Exchange (ETDEWEB)

Zehr, Elena; Szyk, Agnieszka; Piszczek, Grzegorz; Szczesna, Ewa; Zuo, Xiaobing; Roll-Mecak, Antonina

2017-08-07

Microtubule-severing enzymes katanin, spastin and fidgetin are AAA ATPases critical for the biogenesis and maintenance of complex microtubule arrays in axons, spindles and cilia. Because of a lack of 3D structures, their mechanism has remained poorly understood. We report the first X-ray structure of the monomeric AAA katanin module and cryo-EM reconstructions of the hexamer in two conformations. These reveal an unexpected asymmetric arrangement of the AAA domains mediated by structural elements unique to severing enzymes and critical for their function. Our reconstructions show that katanin cycles between open spiral and closed ring conformations, depending on the ATP occupancy of a gating protomer that tenses or relaxes inter-protomer interfaces. Cycling of the hexamer between these conformations would provide the power stroke for microtubule severing.

Microtubule Regulation of Kv7 Channels Orchestrates cAMP-Mediated Vasorelaxations in Rat Arterial Smooth Muscle

DEFF Research Database (Denmark)

Lindman, Johanna; Khammy, Makhala M; Lundegaard, Pia R

2018-01-01

Microtubules can regulate GPCR (G protein-coupled receptor) signaling in various cell types. In vascular smooth muscle, activation of the β-adrenoceptor leads to production of cAMP to mediate a vasorelaxation. Little is known about the role of microtubules in smooth muscle, and given the importance...... of renal and mesenteric arteries that the microtubule stabilizer, paclitaxel, prevented. Sharp microelectrode experiments showed that colchicine treatment caused increased hyperpolarization of mesenteric artery segments in response to isoprenaline. Application of the Kv7 channel blocker, XE991, attenuated...

Experimental and numerical investigations of BWR fuel bundle inlet flow

International Nuclear Information System (INIS)

Hoashi, E; Morooka, S; Ishitori, T; Komita, H; Endo, T; Honda, H; Yamamoto, T; Kato, T; Kawamura, S

2009-01-01

We have been studying the mechanism of the flow pattern near the fuel bundle inlet of BWR using both flow visualization test and computational fluid dynamics (CFD) simulation. In the visualization test, both single- and multi-bundle test sections were used. The former test section includes only a corner orifice facing two support beams and the latter simulates 16 bundles surrounded by four beams. An observation window is set on the side of the walls imitating the support beams upstream of the orifices in both test sections. In the CFD simulation, as well as the visualization test, the single-bundle model is composed of one bundle with a corner orifice and the multi-bundle model is a 1/4 cut of the test section that includes 4 bundles with the following four orifices: a corner orifice facing the corner of the two neighboring support beams, a center orifice at the opposite side from the corner orifice, and two side orifices. Twin-vortices were observed just upstream of the corner orifice in the multi-bundle test as well as the single-bundle test. A single-vortex and a vortex filament were observed at the side orifice inlet and no vortex was observed at the center orifice. These flow patterns were also predicted in the CFD simulation using Reynolds Stress Model as a turbulent model and the results were in good agreement with the test results mentioned above. (author)

Output commitment through product bundling: experimental evidence

NARCIS (Netherlands)

Hinloopen, J.; Mueller, W.; Normann, H.T.

2011-01-01

We analyze the impact of product bundling in experimental markets. A firm has monopoly power in one market but faces competition by a second firm in another market. We compare treatments where the monopolist can bundle its two products to treatments where it cannot, and we contrast simultaneous and

Double-bundle depiction of the anterior cruciate ligament at 3 Tesla

Energy Technology Data Exchange (ETDEWEB)

Adriaensen, M.E.A.P.M. [Atrium Medical Center Parkstad, Department of Radiology, Heerlen (Netherlands); Hogan, B. [Sports Surgery Clinic, Department of Radiology, Dublin (Ireland); Al-Bulushi, H.I.J. [Armed Forces Hospital, Department of Radiology, Muscat (Oman); Kavanagh, E.C. [Mater Misericordiae Hospital, Department of Radiology, Dublin (Ireland)

2012-07-15

Magnetic resonance imaging on 3 Tesla (3T MRI) with arthroscopic correlation has proven to adequately identify the anteromedial bundle (AMB) and posterolateral bundle (PLB) in cadaver knees. The purpose of this study was to describe the depiction of ACL bundle anatomy on 3T MRI in daily practice. In a retrospective cohort study, we included 50 consecutive patients who underwent standard 3T MRI of the knee and had an intact ACL. Two musculoskeletal radiologists independently reviewed all scans for depiction of ACL bundle anatomy using standardized forms. Descriptive statistics were used. Twenty-three right knees (46%) and 27 left knees (54%) were included in the study. Mean age of the patients was 35 years (range 12 to 68 years); 37 patients were male (74%). ACL bundle anatomy was best depicted in the axial plane in 44 knees (88%) and in the coronal plane in six knees (12%). Two bundles were seen in 47 knees (94%). The AMB was completely seen in 45 knees (90%). The PLB was completely seen in 40 knees (80%). Both bundles were completely seen in 37 knees (76%). The double-bundle anatomy of the ACL is visualized in 94% of patients on 3T MRI. Because of potentially associated clinical benefits, we advocate to report separately on the anteromedial bundle and posterolateral bundle in case of anterior cruciate ligament injury of the knee. (orig.)

Geometry of Quantum Principal Bundles. Pt. 1

International Nuclear Information System (INIS)

Durdevic, M.

1996-01-01

A theory of principal bundles possessing quantum structure groups and classical base manifolds is presented. Structural analysis of such quantum principal bundles is performed. A differential calculus is constructed, combining differential forms on the base manifold with an appropriate differential calculus on the structure quantum group. Relations between the calculus on the group and the calculus on the bundle are investigated. A concept of (pseudo)tensoriality is formulated. The formalism of connections is developed. In particular, operators of horizontal projection, covariant derivative and curvature are constructed and analyzed. Generalizations of the first Structure Equation and of the Bianchi identity are found. Illustrative examples are presented. (orig.)

Microtubule self-organisation by reaction-diffusion processes causes collective transport and organisation of cellular particles

Directory of Open Access Journals (Sweden)

Demongeot Jacques

2004-06-01

Full Text Available Abstract Background The transport of intra-cellular particles by microtubules is a major biological function. Under appropriate in vitro conditions, microtubule preparations behave as a 'complex' system and show 'emergent' phenomena. In particular, they form dissipative structures that self-organise over macroscopic distances by a combination of reaction and diffusion. Results Here, we show that self-organisation also gives rise to a collective transport of colloidal particles along a specific direction. Particles, such as polystyrene beads, chromosomes, nuclei, and vesicles are carried at speeds of several microns per minute. The process also results in the macroscopic self-organisation of these particles. After self-organisation is completed, they show the same pattern of organisation as the microtubules. Numerical simulations of a population of growing and shrinking microtubules, incorporating experimentally realistic reaction dynamics, predict self-organisation. They forecast that during self-organisation, macroscopic parallel arrays of oriented microtubules form which cross the reaction space in successive waves. Such travelling waves are capable of transporting colloidal particles. The fact that in the simulations, the aligned arrays move along the same direction and at the same speed as the particles move, suggest that this process forms the underlying mechanism for the observed transport properties. Conclusions This process constitutes a novel physical chemical mechanism by which chemical energy is converted into collective transport of colloidal particles along a given direction. Self-organisation of this type provides a new mechanism by which intra cellular particles such as chromosomes and vesicles can be displaced and simultaneously organised by microtubules. It is plausible that processes of this type occur in vivo.

Microtubule self-organisation by reaction-diffusion processes causes collective transport and organisation of cellular particles

Science.gov (United States)

Glade, Nicolas; Demongeot, Jacques; Tabony, James

2004-01-01

Background The transport of intra-cellular particles by microtubules is a major biological function. Under appropriate in vitro conditions, microtubule preparations behave as a 'complex' system and show 'emergent' phenomena. In particular, they form dissipative structures that self-organise over macroscopic distances by a combination of reaction and diffusion. Results Here, we show that self-organisation also gives rise to a collective transport of colloidal particles along a specific direction. Particles, such as polystyrene beads, chromosomes, nuclei, and vesicles are carried at speeds of several microns per minute. The process also results in the macroscopic self-organisation of these particles. After self-organisation is completed, they show the same pattern of organisation as the microtubules. Numerical simulations of a population of growing and shrinking microtubules, incorporating experimentally realistic reaction dynamics, predict self-organisation. They forecast that during self-organisation, macroscopic parallel arrays of oriented microtubules form which cross the reaction space in successive waves. Such travelling waves are capable of transporting colloidal particles. The fact that in the simulations, the aligned arrays move along the same direction and at the same speed as the particles move, suggest that this process forms the underlying mechanism for the observed transport properties. Conclusions This process constitutes a novel physical chemical mechanism by which chemical energy is converted into collective transport of colloidal particles along a given direction. Self-organisation of this type provides a new mechanism by which intra cellular particles such as chromosomes and vesicles can be displaced and simultaneously organised by microtubules. It is plausible that processes of this type occur in vivo. PMID:15176973

A comparative CFD investigation of helical wire-wrapped 7, 19 and 37 fuel pin bundles and its extendibility to 217 pin bundle

International Nuclear Information System (INIS)

Gajapathy, R.; Velusamy, K.; Selvaraj, P.; Chellapandi, P.; Chetal, S.C.

2009-01-01

Preliminary investigations of sodium flow and temperature distributions in heat generating fuel pin bundles with helical spacer wires have been carried out. Towards this, the 3D conservation equations of mass, momentum and energy have been solved using a commercial computational fluid dynamics (CFD) code. Turbulence has been accounted through the use of high Reynolds number version of standard k-ε model, with uniform mesh density respecting wall function requirements. The geometric details of the bundle and the heat flux in are similar to that of the Indian Prototype Fast Breeder Reactor (PFBR) that is currently under construction. The mixing characteristics of the flow among the peripheral and central zones are compared for 7, 19 and 37 fuel pin bundles and the characteristics are extended to a 217 pin bundle. The friction factors of the pin bundles obtained from the present study is seen to agree well with the values derived from experimental correlations. It is found that the normalized outlet velocities in the peripheral and central zones are nearly equal to 1.1-0.9, respectively which is in good agreement with the published hydraulic experimental measurements of 1.1-0.85 for a 91 pin bundle. The axial velocity is the maximum in the peripheral zone where spacer wires are located and minimum in the zones which are diametrically opposite to the respective zone of maximum velocity. The sodium temperature is higher in the zones where the flow area and mass flow rates are less due to the presence of the spacer wires though the axial velocity is higher there. It is the minimum in the peripheral zones where the circumferential flow is larger. Based on the flow and temperature distributions obtained for 19 and 37 pin bundles, a preliminary extrapolation procedure has been established for estimating the temperatures of peripheral and central zones of 217 pin bundle.

Productivity of the supply system based on whole-tree bundling

Energy Technology Data Exchange (ETDEWEB)

Laitila, J. (Finnish Forest Research Inst., Joensuu (Finland)), Email: juha.laitila@metla.fi; Jylhae, P. (Finnish Forest Research Inst., Kannus (Finland)), Email: paula.jylha@metla.fi; Kaerhae, K. (Metsaeteho Oy, Helsinki (Finland)), Email: kalle.karha@metsateho.fi

2009-07-01

In the present study, time consumption models for bundle harvesting and forwarding were created by applying regression analyses. The time studies related to on-road transportation were created by applying regression analyses. The time studies related to on-road transportation were focused on comparing the terminal times spent on handling of whole-tree bundles and conventional 5-m pulpwood. The number of whole-tree bundles per truck load and the weights of the payloads were also recorded. The forwarding productivity of whole-tree bundles was about double compared to conventional pulpwood and whole-trees. In on-road transportation, the mean loading and unloading time of whole-tree bundles per truck load was 46 % higher compared to that of conventional 5-m pulpwood. The second prototype of the bundle harvester is under construction, and the time studies are to be continued after accomplishing the machine in the autumn 2009. (orig.)

Kernel bundle EPDiff

DEFF Research Database (Denmark)

Sommer, Stefan Horst; Lauze, Francois Bernard; Nielsen, Mads

2011-01-01

In the LDDMM framework, optimal warps for image registration are found as end-points of critical paths for an energy functional, and the EPDiff equations describe the evolution along such paths. The Large Deformation Diffeomorphic Kernel Bundle Mapping (LDDKBM) extension of LDDMM allows scale space...

Interplanetary Overlay Network Bundle Protocol Implementation

Science.gov (United States)

Burleigh, Scott C.

2011-01-01

The Interplanetary Overlay Network (ION) system's BP package, an implementation of the Delay-Tolerant Networking (DTN) Bundle Protocol (BP) and supporting services, has been specifically designed to be suitable for use on deep-space robotic vehicles. Although the ION BP implementation is unique in its use of zero-copy objects for high performance, and in its use of resource-sensitive rate control, it is fully interoperable with other implementations of the BP specification (Internet RFC 5050). The ION BP implementation is built using the same software infrastructure that underlies the implementation of the CCSDS (Consultative Committee for Space Data Systems) File Delivery Protocol (CFDP) built into the flight software of Deep Impact. It is designed to minimize resource consumption, while maximizing operational robustness. For example, no dynamic allocation of system memory is required. Like all the other ION packages, ION's BP implementation is designed to port readily between Linux and Solaris (for easy development and for ground system operations) and VxWorks (for flight systems operations). The exact same source code is exercised in both environments. Initially included in the ION BP implementations are the following: libraries of functions used in constructing bundle forwarders and convergence-layer (CL) input and output adapters; a simple prototype bundle forwarder and associated CL adapters designed to run over an IPbased local area network; administrative tools for managing a simple DTN infrastructure built from these components; a background daemon process that silently destroys bundles whose time-to-live intervals have expired; a library of functions exposed to applications, enabling them to issue and receive data encapsulated in DTN bundles; and some simple applications that can be used for system checkout and benchmarking.

Superconductivity in an Inhomogeneous Bundle of Metallic and Semiconducting Nanotubes

Directory of Open Access Journals (Sweden)

Ilya Grigorenko

2013-01-01

Full Text Available Using Bogoliubov-de Gennes formalism for inhomogeneous systems, we have studied superconducting properties of a bundle of packed carbon nanotubes, making a triangular lattice in the bundle's transverse cross-section. The bundle consists of a mixture of metallic and doped semiconducting nanotubes, which have different critical transition temperatures. We investigate how a spatially averaged superconducting order parameter and the critical transition temperature depend on the fraction of the doped semiconducting carbon nanotubes in the bundle. Our simulations suggest that the superconductivity in the bundle will be suppressed when the fraction of the doped semiconducting carbon nanotubes will be less than 0.5, which is the percolation threshold for a two-dimensional triangular lattice.

Two-categorical bundles and their classifying spaces

DEFF Research Database (Denmark)

Baas, Nils A.; Bökstedt, M.; Kro, T.A.

2012-01-01

-category is a classifying space for the associated principal 2-bundles. In the process of proving this we develop a lot of powerful machinery which may be useful in further studies of 2-categorical topology. As a corollary we get a new proof of the classification of principal bundles. A calculation based...

Sperm competition promotes diversity of sperm bundles in Ohomopterus ground beetles

Science.gov (United States)

Takami, Yasuoki; Sota, Teiji

2007-07-01

Diversification of sperm morphology has been investigated in the context of sperm competition, but the adaptive significance of sperm bundles is still unclear. In analyzing 10 taxa of the genus Carabus subgenus Ohomopterus and one related Carabus ground beetles, we found that dimorphic sperm bundles occurred in most species with varied degrees of bimodality, whereas sperm were generally monomorphic. Comparative analyses with phylogenetically independent contrasts revealed that the sizes of large and small sperm bundles evolved more rapidly than, and were not correlated with, the length of sperm, suggesting more intense selection on sperm bundle sizes and their independent responses to different evolutionary forces. The size of large sperm bundles was positively correlated with male genital morphology (pertinent to displacement of rival spermatophores) and postcopulatory guarding duration as well as male body length, suggesting that larger sperm bundles have been favored when the risk of spermatophore displacement is high. Larger sperm bundles may be advantageous because of their ability to migrate more rapidly into the spermatheca. In contrast, no clear association was detected between the small sperm bundle size and mating traits despite its rapid diversification. The present study provides the first record of heteromorphic sperm bundles, the diversity of which may be promoted by sperm competition.

CFD modeling of secondary flows in fuel rod bundles

International Nuclear Information System (INIS)

Baglietto, Emilio; Ninokata, Hisashi

2004-01-01

An optimized non-linear eddy viscosity model is introduced, for calculations of detailed coolant velocity distribution in a tight lattice fuel bundle. The low Reynolds formulation has been optimized based on DNS data for channel flow. The non-linear stress-strain relationship has been modified in the coefficients to model the flow anisotropy, which causes the formation of turbulence driven secondary flows inside the bundle subchannels. Predictions of the model are first compared to experimental measurements of secondary flows in a triangularly arrayed rod bundle with p/d=1.3. Subsequently wall shear stress and velocity predictions are compared with different experimental data for a rod bundle with p/d=1.17. The model shows to be able to correctly reproduce the scale of the secondary motion, and to accurately reproduce both wall shear stress and velocity distributions inside the rod bundle subchannels. (author)

"The Invisible Staff": A Qualitative Analysis of Environmental Service Workers' Perceptions of the VA Clostridium difficile Prevention Bundle Using a Human Factors Engineering Approach.

Science.gov (United States)

Yanke, Eric; Moriarty, Helene; Carayon, Pascale; Safdar, Nasia

2018-06-11

Using a novel human factors engineering approach, the Systems Engineering Initiative for Patient Safety model, we evaluated environmental service workers' (ESWs) perceptions of barriers and facilitators influencing adherence to the nationally mandated Department of Veterans Affairs Clostridium difficile infection (CDI) prevention bundle. A focus group of ESWs was conducted. Qualitative analysis was performed employing a visual matrix display to identify barrier/facilitator themes related to Department of Veterans Affairs CDI bundle adherence using the Systems Engineering Initiative for Patient Safety work system as a framework. Environmental service workers reported adequate cleaning supplies/equipment and displayed excellent knowledge of CDI hand hygiene requirements. Environmental service workers described current supervisory practices as providing an acceptable amount of time to clean CDI rooms, although other healthcare workers often pressured ESWs to clean rooms more quickly. Environmental service workers reported significant concern for CDI patients' family members as well as suggesting uncertainty regarding the need for family members to follow infection prevention practices. Small and cluttered patient rooms made cleaning tasks more difficult, and ESW cleaning tasks were often interrupted by other healthcare workers. Environmental service workers did not feel comfortable asking physicians for more time to finish cleaning a room nor did ESWs feel comfortable pointing out lapses in physician hand hygiene. Multiple work system components serve as barriers to and facilitators of ESW adherence to the nationally mandated Department of Veterans Affairs CDI bundle. Environmental service workers may represent an underappreciated resource for hospital infection prevention, and further efforts should be made to engage ESWs as members of the health care team.

Identification of a lysosome membrane protein which could mediate ATP-dependent stable association of lysosomes to microtubules

International Nuclear Information System (INIS)

Mithieux, G.; Rousset, B.

1989-01-01

We have previously reported that purified thyroid lysosomes bind to reconstituted microtubules to form stable complexes, a process which is inhibited by ATP. Among detergent-solubilized lysosomal membrane protein, we identified a 50-kDa molecular component which binds to preassembled microtubules. The binding of this polypeptide to microtubules was decreased in the presence of ATP. We purified this 50-kDa protein by affinity chromatography on immobilized ATP. The 50-kDa protein bound to the ATP column was eluted by 1 mM ATP. The purified protein, labeled with 125I, exhibited the ability of interacting with microtubules. The binding process was inhibited by increasing concentrations of ATP, the half-maximal inhibitory effect being obtained at an ATP concentration of 0.35 mM. The interaction of the 50-kDa protein with microtubules is a saturable phenomenon since the binding of the 125I-labeled 50-kDa protein was inhibited by unlabeled solubilized lysosomal membrane protein containing the 50-kDa polypeptide but not by the same protein fraction from which the 50-kDa polypeptide had been removed by the ATP affinity chromatography procedure. The 50-kDa protein has the property to bind to pure tubulin coupled to an insoluble matrix. The 50-kDa protein was eluted from the tubulin affinity column by ATP. These findings support the conclusion that a protein inserted into the lysosomal membrane is able to bind directly to microtubules in a process which can be regulated by ATP. We propose that this protein could account for the association of lysosomes to microtubules demonstrated both in vitro and in intact cells

Xyloglucan Deficiency Disrupts Microtubule Stability and Cellulose Biosynthesis in Arabidopsis, Altering Cell Growth and Morphogenesis

Energy Technology Data Exchange (ETDEWEB)

Xiao, Chaowen; Zhang, Tian; Zheng, Yunzhen; Cosgrove, Daniel J.; Anderson, Charles T.

2015-11-02

Xyloglucan constitutes most of the hemicellulose in eudicot primary cell walls and functions in cell wall structure and mechanics. Although Arabidopsis (Arabidopsis thaliana) xxt1 xxt2 mutants lacking detectable xyloglucan are viable, they display growth defects that are suggestive of alterations in wall integrity. To probe the mechanisms underlying these defects, we analyzed cellulose arrangement, microtubule patterning and dynamics, microtubule- and wall-integrity-related gene expression, and cellulose biosynthesis in xxt1 xxt2 plants. We found that cellulose is highly aligned in xxt1 xxt2 cell walls, that its three-dimensional distribution is altered, and that microtubule patterning and stability are aberrant in etiolated xxt1 xxt2 hypocotyls. We also found that the expression levels of microtubule-associated genes, such as MAP70-5 and CLASP, and receptor genes, such as HERK1 and WAK1, were changed in xxt1 xxt2 plants and that cellulose synthase motility is reduced in xxt1 xxt2 cells, corresponding with a reduction in cellulose content. Our results indicate that loss of xyloglucan affects both the stability of the microtubule cytoskeleton and the production and patterning of cellulose in primary cell walls. These findings establish, to our knowledge, new links between wall integrity, cytoskeletal dynamics, and wall synthesis in the regulation of plant morphogenesis.

Frobenius splitting of projective toric bundles

Indian Academy of Sciences (India)

He Xin

2018-03-19

Mar 19, 2018 ... Firstly it is easy to see that the image of s under the restriction map (2.5) falls in the χ-isotypical component of (Uσ , E), i.e. for all t ∈ T .... σ falls in the χ-isotypical component of (E,Uσ ). D. As mentioned in Remark 2.3, for a vector v .... The determinant of a toric bundle. LetE be a toric bundle on a toric variety X ...

Capu and Spire Assemble a Cytoplasmic Actin~Mesh that Maintains Microtubule Organization in the Drosophila Oocyte

DEFF Research Database (Denmark)

Dahlgaard, K.; Raposo, A.A.S.F.; Niccoli, T.

2007-01-01

Mutants in the actin nucleators Cappuccino and Spire disrupt the polarized microtubule network in the Drosophila oocyte that defines the anterior-posterior axis, suggesting that microtubule organization depends on actin. Here, we show that Cappuccino and Spire organize an isotropic mesh of actin...

Analytical prediction of turbulent friction factor for a rod bundle

International Nuclear Information System (INIS)

Bae, Jun Ho; Park, Joo Hwan

2011-01-01

An analytical calculation has been performed to predict the turbulent friction factor in a rod bundle. For each subchannel constituting a rod bundle, the geometry parameters are analytically derived by integrating the law of the wall over each subchannel with the consideration of a local shear stress distribution. The correlation equations for a local shear stress distribution are supplied from a numerical simulation for each subchannel. The explicit effect of a subchannel shape on the geometry parameter and the friction factor is reported. The friction factor of a corner subchannel converges to a constant value, while the friction factor of a central subchannel steadily increases with a rod distance ratio. The analysis for a rod bundle shows that the friction factor of a rod bundle is largely affected by the characteristics of each subchannel constituting a rod bundle. The present analytic calculations well predict the experimental results from the literature with rod bundles in circular, hexagonal, and square channels.

Matrix remodeling between cells and cellular interactions with collagen bundle

Science.gov (United States)

Kim, Jihan; Sun, Bo

When cells are surrounded by complex environment, they continuously probe and interact with it by applying cellular traction forces. As cells apply traction forces, they can sense rigidity of their local environment and remodel the matrix microstructure simultaneously. Previous study shows that single human carcinoma cell (MDA-MB-231) remodeled its surrounding extracellular matrix (ECM) and the matrix remodeling was reversible. In this study we examined the matrix microstructure between cells and cellular interaction between them using quantitative confocal microscopy. The result shows that the matrix microstructure is the most significantly remodeled between cells consisting of aligned, and densified collagen fibers (collagen bundle)., the result shows that collagen bundle is irreversible and significantly change micromechanics of ECM around the bundle. We further examined cellular interaction with collagen bundle by analyzing dynamics of actin and talin formation along with the direction of bundle. Lastly, we analyzed dynamics of cellular protrusion and migrating direction of cells along the bundle.

Large bundle BWR test CORA-18: Test results

International Nuclear Information System (INIS)

Hagen, S.; Hofmann, P.; Noack, V.; Sepold, L.; Schanz, G.; Schumacher, G.

1998-04-01

The CORA out-of-pile experiments are part of the international Severe Fuel Damage (SFD) Program. They were performed to provide information on the damage progression of Light Water Reactor (LWR) fuel elements in Loss-of-coolant Accidents in the temperature range 1200 C to 2400 C. CORA-18 was the large BWR bundle test corresponding to the PWR test CORA-7. It should investigate if there exists an influence of the BWR bundle size on the fuel damage behaviour. Therefore, the standard-type BWR CORA bundle with 18 fuel rod simulators was replaced by a large bundle with two additional surrounding rows of 30 rods (48 rods total). Power input and steam flow were increased proportionally to the number of fuel rod simulators to give the same initial heat-up rate of about 1 K/s as in the smaller bundles. Emphasis was put on the initial phase of the damage progression. More information on the chemical composition of initial and intermediate interaction products and their relocation behaviour should be obtained. Therefore, power and steam input were terminated after the onset of the temperature escalation. (orig.) [de

Surgical anatomy of the atrioventricular conduction bundle in anomalous muscle bundle of the right ventricle with subarterial ventricular septal defect

NARCIS (Netherlands)

Kurosawa, H.; Becker, A. E.

1985-01-01

A stillborn baby girl was found to have an anomalous muscle bundle of the right ventricle, associated with a doubly committed subarterial ventricular septal defect. The latter was separated from the area of the atrioventricular conduction bundle by muscle. Serial histologic sectioning of the

Broadband and flexible acoustic focusing by metafiber bundles

Science.gov (United States)

Sun, Hong-Xiang; Chen, Jia-He; Ge, Yong; Yuan, Shou-Qi; Liu, Xiao-Jun

2018-06-01

We report a broadband and flexible acoustic focusing through metafiber bundles in air, in which each metafiber consists of eight circular and narrow rectangular cavities. The fractional bandwidth of the acoustic focusing could reach about 0.2, which arises from the eigenmodes of the metafiber structure. Besides, owing to the flexible characteristic of the metafibers, the focus position can be manipulated by bending the metafiber bundles, and the metafiber bundles could bypass rigid scatterers inside the lens structure. More interestingly, the acoustic propagation and focusing directions can be changed by using a designed right-angled direction converter fabricated by the metafibers, and a waveform converter and a focusing lens of the cylindrical acoustic source are realized based on the metafiber bundles. The proposed focusing lens has the advantages of broad bandwidth, flexible structure, and high focusing performance, showing great potentials in versatile applications.

Interaction of the Tobacco mosaic virus movement protein with microtubules during the cell cycle in tobacco BY-2 cells.

Science.gov (United States)

Boutant, Emmanuel; Fitterer, Chantal; Ritzenthaler, Christophe; Heinlein, Manfred

2009-10-01

Cell-to-cell movement of Tobacco mosaic virus (TMV) involves the interaction of virus-encoded 30-kDa movement protein (MP) with microtubules. In cells behind the infection front that accumulate high levels of MP, this activity is reflected by the formation of stabilized MP/microtubule complexes. The ability of MP to bind along and stabilize microtubules is conserved upon expression in mammalian cells. In mammalian cells, the protein also leads to inhibition of mitosis and cell division through a microtubule-independent process correlated with the loss of centrosomal gamma-tubulin and of centrosomal microtubule-nucleation activity. Since MP has the capacity to interact with plant factors involved in microtubule nucleation and dynamics, we used inducible expression in BY-2 cells to test whether MP expression inhibits mitosis and cell division also in plants. We demonstrate that MP:GFP associates with all plant microtubule arrays and, unlike in mammalian cells, does not interfere with mitosis. Thus, MP function and the interaction of MP with factors of the cytoskeleton do not entail an inhibition of mitosis in plants. We also report that the protein targets primary plasmodesmata in BY-2 cells immediately upon or during cytokinesis and that the accumulation of MP in plasmodesmata occurs in the presence of inhibitors of the cytoskeleton and the secretory pathway.

Centromere Protein (CENP)-W Interacts with Heterogeneous Nuclear Ribonucleoprotein (hnRNP) U and May Contribute to Kinetochore-Microtubule Attachment in Mitotic Cells

Science.gov (United States)

Chun, Younghwa; Kim, Raehyung; Lee, Soojin

2016-01-01

Background Recent studies have shown that heterogeneous nuclear ribonucleoprotein U (hnRNP U), a component of the hnRNP complex, contributes to stabilize the kinetochore-microtubule interaction during mitosis. CENP-W was identified as an inner centromere component that plays crucial roles in the formation of a functional kinetochore complex. Results We report that hnRNP U interacts with CENP-W, and the interaction between hnRNP U and CENP-W mutually increased each other’s protein stability by inhibiting the proteasome-mediated degradation. Further, their co-localization was observed chiefly in the nuclear matrix region and at the microtubule-kinetochore interface during interphase and mitosis, respectively. Both microtubule-stabilizing and microtubule-destabilizing agents significantly decreased the protein stability of CENP-W. Furthermore, loss of microtubules and defects in microtubule organization were observed in CENP-W-depleted cells. Conclusion Our data imply that CENP-W plays an important role in the attachment and interaction between microtubules and kinetochore during mitosis. PMID:26881882

The avalanche process of the multilinear fiber bundles model

International Nuclear Information System (INIS)

Hao, Da-Peng; Tang, Gang; Xun, Zhi-Peng; Xia, Hui; Han, Kui

2012-01-01

In order to describe the smooth nonlinear constitutive behavior in the process of fracture of ductile micromechanics structures, the multilinear fiber bundle model was constructed, based on the bilinear fiber bundle model. In the multilinear fiber bundle model, the Young modulus of a fiber is assumed to decay K max times before the final failure occurs. For the large K max region, this model can describe the smooth nonlinear constitutive behavior well. By means of analytical approximation and numerical simulation, we show that the two critical parameters, i.e. the decay ratio of the Young modulus and the maximum number of decays, have substantial effects on the failure process of the bundle. From a macroscopic view, the model can provide various shapes of constitutive curves, which represent diverse kinds of tensile fracture processes. However, at the microscopic scale, the statistical properties of the model are in accord with the classical fiber bundle model. (paper)

and its allicin on microtubule and cancer cell lines

African Journals Online (AJOL)

STORAGESEVER

2009-10-05

Oct 5, 2009 ... microtubule protein polymer that treated by A. hirtifolium. (A), and allicin (B) in .... with a chromogenic thiol: reaction of 4-mercaptopyridine with ... transformed tumor growth in vivo by diallyl disulfide is associated with inhibition ...

Characterization of midrib vascular bundles of selected medicinal species in Rubiaceae

Science.gov (United States)

Nurul-Syahirah, M.; Noraini, T.; Latiff, A.

2016-11-01

An anatomical study was carried out on mature leaves of five selected medicinal species of Rubiaceae from Peninsular Malaysia. The chosen medicinal species were Aidia densiflora, Aidia racemosa, Chasallia chartacea, Hedyotis auricularia and Ixora grandifolia. The objective of this study is to determine the taxonomic value of midrib anatomical characteristics. Leaves samples were collected from Taman Paku Pakis, Universiti Kebangsaan Malaysia, Bangi, Selangor and Kledang Saiong Forest Reserve, Perak, Malaysia. Leaves samples then were fixed in spirit and acetic acid (3:1), the midrib parts then were sectioned using sliding microtome, cleared using Clorox, stained in Safranin and Alcian blue, mounted in Euparal and were observed under light microscope. Findings in this study have shown all species have collateral bundles. The midrib vascular bundles characteristics that can be used as tool to differentiate between species or genus are vascular bundles system (opened or closed), shape and arrangement of main vascular bundles, presence of both additional and medullary vascular bundles, position of additional vascular bundles, shape of medullary vascular bundles, presence of sclerenchyma cells ensheathed the vascular bundles. As a conclusion, midrib anatomical characteristics can be used to identify and discriminate medicinal plants species studied in the Rubiaceae.

Cryopreservation of sperm bundles (spermatozeugmata) from endangered livebearing goodeids.

Science.gov (United States)

Liu, Yue; Torres, Leticia; Tiersch, Terrence R

2018-04-14

More than half of fishes in the family Goodeidae are considered to be endangered, threatened, or vulnerable. Sperm cryopreservation is an effective tool for conserving genetic resources of imperiled populations, but development of protocols with livebearing fishes faces numerous challenges including the natural packaging of sperm into bundles. In this study the cryopreservation of sperm bundles (spermatozeugmata) of three goodeids species was evaluated. Sperm quality was evaluated by activation with NaCl-NaOH solution (at 300 mOsmol/kg and pH 11.8), and analysis of dissociable bundles and dissociation duration. Using Redtail Splitfin (Xenotoca eiseni) as a model, the effects of cryoprotectants (dimethyl sulfoxide, methanol, and glycerol) with different concentrations (5-15% v/v %), equilibration exposure times (1-60 min), cooling rates (5-40 °C/min), concentrations (4 × 10 4 -4 × 10 6 bundles/ml), buffers (HBSS, PBS and NaCl), and buffer osmolalities (200-400 mOsmol/kg) were investigated. After cooling and thawing, sperm bundles maintained their packed form. A specific protocol was developed (10% dimethyl sulfoxide, 20-min equilibration, 10 °C/min cooling rate, 4 × 10 6 bundles/ml, and 300 mOsmol/kg HBSS). This protocol yielded 89 ± 5% of post-thaw dissociable bundles with 209 ± 10 s of dissociation duration for X. eiseni, 96 ± 9% with 814 ± 14 s for Blackfin Goodea (Goodea atripinni), and 66 ± 2% with 726 ± 25 s for Striped Goodeid (Ataeniobius toweri). This is the first study of cryopreservation of sperm within bundles for livebearing fishes and provides a basis for establishment of germplasm repositories for goodeids and other livebearers. Copyright © 2018 Elsevier Inc. All rights reserved.

CANFLEX fuel bundle cross-flow endurance test (test report)

International Nuclear Information System (INIS)

Hong, Sung Deok; Chung, C. H.; Chang, S. K.; Kim, B. D.

1997-04-01

As part of the normal refuelling sequence of CANDU nuclear reactor, both new and irradiated bundles can be parked in the cross-flow region of the liner tubes. This situation occurs normally for a few minutes. The fuel bundle which is subjected to the cross-flow should be capable of withstanding the consequences of cross flow for normal periods, and maintain its mechanical integrity. The cross-flow endurance test was conducted for CANFLEX bundle, latest developed nuclear fuel, at CANDU-Hot Test Loop. The test was carried out during 4 hours at the inlet cross-flow region. After the test, the bundle successfully met all acceptance criteria after the 4 hours cross-flow test. (author). 2 refs., 3 tabs

CANFLEX fuel bundle cross-flow endurance test (test report)

Energy Technology Data Exchange (ETDEWEB)

Hong, Sung Deok; Chung, C. H.; Chang, S. K.; Kim, B. D.

1997-04-01

As part of the normal refuelling sequence of CANDU nuclear reactor, both new and irradiated bundles can be parked in the cross-flow region of the liner tubes. This situation occurs normally for a few minutes. The fuel bundle which is subjected to the cross-flow should be capable of withstanding the consequences of cross flow for normal periods, and maintain its mechanical integrity. The cross-flow endurance test was conducted for CANFLEX bundle, latest developed nuclear fuel, at CANDU-Hot Test Loop. The test was carried out during 4 hours at the inlet cross-flow region. After the test, the bundle successfully met all acceptance criteria after the 4 hours cross-flow test. (author). 2 refs., 3 tabs.

Novel mitochondrial extensions provide evidence for a link between microtubule-directed movement and mitochondrial fission

International Nuclear Information System (INIS)

Bowes, Timothy; Gupta, Radhey S.

2008-01-01

Mitochondrial dynamics play an important role in a large number of cellular processes. Previously, we reported that treatment of mammalian cells with the cysteine-alkylators, N-ethylmaleimide and ethacrynic acid, induced rapid mitochondrial fusion forming a large reticulum approximately 30 min after treatment. Here, we further investigated this phenomenon using a number of techniques including live-cell confocal microscopy. In live cells, drug-induced fusion coincided with a cessation of fast mitochondrial movement which was dependent on microtubules. During this loss of movement, thin mitochondrial tubules extending from mitochondria were also observed, which we refer to as 'mitochondrial extensions'. The formation of these mitochondrial extensions, which were not observed in untreated cells, depended on microtubules and was abolished by pretreatment with nocodazole. In this study, we provide evidence that these extensions result from of a block in mitochondrial fission combined with continued application of motile force by microtubule-dependent motor complexes. Our observations strongly suggest the existence of a link between microtubule-based mitochondrial trafficking and mitochondrial fission

A de novo designed monomeric, compact three helix bundle protein on a carbohydrate template

DEFF Research Database (Denmark)

Malik, Leila; Nygård, Jesper; Christensen, Niels Johan

2015-01-01

De novo design and chemical synthesis of proteins and of other artificial structures, which mimic them, is a central strategy for understanding protein folding and for accessing proteins with novel functions. We have previously described carbohydrates as templates for the assembly of artificial...... the template could facilitate protein folding. Here we report the design and synthesis of 3-helix bundle carboproteins on deoxy-hexopyranosides. The carboproteins were analyzed by CD, AUC, SAXS, and NMR, which revealed the formation of the first compact, and folded monomeric carboprotein distinctly different...

Smooth Bundling of Large Streaming and Sequence Graphs

NARCIS (Netherlands)

Hurter, C.; Ersoy, O.; Telea, A.

2013-01-01

Dynamic graphs are increasingly pervasive in modern information systems. However, understanding how a graph changes in time is difficult. We present here two techniques for simplified visualization of dynamic graphs using edge bundles. The first technique uses a recent image-based graph bundling

Analyses of HANARO bundle experiment data using MATRA-h: revision

Energy Technology Data Exchange (ETDEWEB)

Lim, In Cheol; Park, Cheol; Chae, Hee Taek; Lee, Choong Sung

1999-08-01

When the construction and operation license for HANARO was renewed in 1995, imposed was a condition that the safety limit CHFR should have the margin of 25 percent. The reason for this were that the number of bundle CHF experiment data was not enough for the validation of the prediction of CHF in bundle geometry and that the ability of COBRA/KMRR to prediction the local coolant condition was not fully validated. For the resolution of this imposition, more bundle CHF data were gathered and the subchannel exit temperature distribution was obtained during the in-core irradiation test of instrumented bundle (Type-B bundle). also, for these experimental data, subchannel analyses were performed by using MATRA-h code which is the modified version of MATRA-a which is a modified version of KAERI's MATRA-a for the application to HANARO. By comparing the analysis results with the experimental results, it was found that the HANARO subchannel analysis method would give the conservative or best-estimated predictions for the CHF in bundle geometry. This report is the revision of KAERI/TR-1090/98 on the analysis of bundle experiment data using MATRA-h. (Author). 16 refs., 16 tabs., 25 figs.

The plant formin AtFH4 interacts with both actin and microtubules, and contains a newly identified microtubule-binding domain

Czech Academy of Sciences Publication Activity Database

Deeks, M.J.; Fendrych, Matyáš; Smertenko, A.; Bell, K.S.; Oparka, K.; Cvrčková, F.; Žárský, Viktor; Hussey, P.J.

2010-01-01

Roč. 123, č. 8 (2010), s. 1209-1215 ISSN 0021-9533 R&D Projects: GA MŠk(CZ) LC06004; GA ČR GAP305/10/0433 Institutional research plan: CEZ:AV0Z50380511 Keywords : Actin regulating proteins * Membrane * Microtubule Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.290, year: 2010

Design and synthesis of DNA four-helix bundles

Energy Technology Data Exchange (ETDEWEB)

Rangnekar, Abhijit; Gothelf, Kurt V [Department of Chemistry, Centre for DNA Nanotechnology (CDNA) and Interdisciplinary Nanoscience Center (iNANO), Aarhus University, DK-8000 Aarhus C (Denmark); LaBean, Thomas H, E-mail: kvg@chem.au.dk, E-mail: thl@cs.duke.edu [Department of Chemistry, Duke University, Durham, NC 27708 (United States)

2011-06-10

The field of DNA nanotechnology has evolved significantly in the past decade. Researchers have succeeded in synthesizing tile-based structures and using them to form periodic lattices in one, two and three dimensions. Origami-based structures have also been used to create nanoscale structures in two and three dimensions. Design and construction of DNA bundles with fixed circumference has added a new dimension to the field. Here we report the design and synthesis of a DNA four-helix bundle. It was found to be extremely rigid and stable. When several such bundles were assembled using appropriate sticky-ends, they formed micrometre-long filaments. However, when creation of two-dimensional sheet-like arrays of the four-helix bundles was attempted, nanoscale rings were observed instead. The exact reason behind the nanoring formation is yet to be ascertained, but it provides an exciting prospect for making programmable circular nanostructures using DNA.

Design and synthesis of DNA four-helix bundles

International Nuclear Information System (INIS)

Rangnekar, Abhijit; Gothelf, Kurt V; LaBean, Thomas H

2011-01-01

The field of DNA nanotechnology has evolved significantly in the past decade. Researchers have succeeded in synthesizing tile-based structures and using them to form periodic lattices in one, two and three dimensions. Origami-based structures have also been used to create nanoscale structures in two and three dimensions. Design and construction of DNA bundles with fixed circumference has added a new dimension to the field. Here we report the design and synthesis of a DNA four-helix bundle. It was found to be extremely rigid and stable. When several such bundles were assembled using appropriate sticky-ends, they formed micrometre-long filaments. However, when creation of two-dimensional sheet-like arrays of the four-helix bundles was attempted, nanoscale rings were observed instead. The exact reason behind the nanoring formation is yet to be ascertained, but it provides an exciting prospect for making programmable circular nanostructures using DNA.

Explaining the Microtubule Energy Balance: Contributions Due to Dipole Moments, Charges, van der Waals and Solvation Energy

Directory of Open Access Journals (Sweden)

Ahmed Taha Ayoub

2017-09-01

Full Text Available Microtubules are the main components of mitotic spindles, and are the pillars of the cellular cytoskeleton. They perform most of their cellular functions by virtue of their unique dynamic instability processes which alternate between polymerization and depolymerization phases. This in turn is driven by a precise balance between attraction and repulsion forces between the constituents of microtubules (MTs—tubulin dimers. Therefore, it is critically important to know what contributions result in a balance of the interaction energy among tubulin dimers that make up microtubules and what interactions may tip this balance toward or away from a stable polymerized state of tubulin. In this paper, we calculate the dipole–dipole interaction energy between tubulin dimers in a microtubule as part of the various contributions to the energy balance. We also compare the remaining contributions to the interaction energies between tubulin dimers and establish a balance between stabilizing and destabilizing components, including the van der Waals, electrostatic, and solvent-accessible surface area energies. The energy balance shows that the GTP-capped tip of the seam at the plus end of microtubules is stabilized only by − 9 kcal/mol, which can be completely reversed by the hydrolysis of a single GTP molecule, which releases + 14 kcal/mol and destabilizes the seam by an excess of + 5 kcal/mol. This triggers the breakdown of microtubules and initiates a disassembly phase which is aptly called a catastrophe.

Local load-sharing fiber bundle model in higher dimensions.

Science.gov (United States)

Sinha, Santanu; Kjellstadli, Jonas T; Hansen, Alex

2015-08-01

We consider the local load-sharing fiber bundle model in one to five dimensions. Depending on the breaking threshold distribution of the fibers, there is a transition where the fracture process becomes localized. In the localized phase, the model behaves as the invasion percolation model. The difference between the local load-sharing fiber bundle model and the equal load-sharing fiber bundle model vanishes with increasing dimensionality with the characteristics of a power law.

Histones bundle F-actin filaments and affect actin structure.

Science.gov (United States)

Blotnick, Edna; Sol, Asaf; Muhlrad, Andras

2017-01-01

Histones are small polycationic proteins complexed with DNA located in the cell nucleus. Upon apoptosis they are secreted from the cells and react with extracellular polyanionic compounds. Actin which is a polyanionic protein, is also secreted from necrotic cells and interacts with histones. We showed that both histone mixture (histone type III) and the recombinant H2A histone bundles F-actin, increases the viscosity of the F-actin containing solution and polymerizes G-actin. The histone-actin bundles are relatively insensitive to increase of ionic strength, unlike other polycation, histatin, lysozyme, spermine and LL-37 induced F-actin bundles. The histone-actin bundles dissociate completely only in the presence of 300-400 mM NaCl. DNA, which competes with F-actin for histones, disassembles histone induced actin bundles. DNase1, which depolymerizes F- to G-actin, actively unbundles the H2A histone induced but slightly affects the histone mixture induced actin bundles. Cofilin decreases the amount of F-actin sedimented by low speed centrifugation, increases light scattering and viscosity of F-actin-histone mixture containing solutions and forms star like superstructures by copolymerizing G-actin with H2A histone. The results indicate that histones are tightly attached to F-actin by strong electrostatic and hydrophobic forces. Since both histones and F-actin are present in the sputum of patients with cystic fibrosis, therefore, the formation of the stable histone-actin bundles can contribute to the pathology of this disease by increasing the viscosity of the sputum. The actin-histone interaction in the nucleus might affect gene expression.

Multi-bundle shashlik calorimeter prototypes beam-test results

International Nuclear Information System (INIS)

Badier, J.; Bloch, P.; Bityukov, S.; Bordalo, P.; Busson, P.; Charlot, C.; Dobrzynski, L.; Golutvin, I.; Guschin, E.; Issakov, V.; Ivanchenko, I.; Klimenko, V.; Marin, V.; Moissenz, P.; Obraztsov, V.; Ostankov, A.; Popov, V.; Puljak, I.; Ramos, S.; Seez, C.; Sergueev, S.; Soushkov, V.; Tanaka, R.; Varela, J.; Virdee, T.S.; Zaitchenko, A.; Zamiatin, N.

1995-01-01

The first beam-test results for two- and three-bundle shashlik tower prototypes are described. We found that the spatial resolution, the uniformity of energy response, the calorimeter reliability and hermeticity and also two showers separation are improved in multi-bundle design approach. ((orig.))

A Brief Survey of Higgs Bundles

OpenAIRE

Zúñiga-Rojas, Ronald Alberto

2018-01-01

Considering a compact Riemann surface of genus greater than two, a Higgs~bundle is a pair composed of a holomorphic bundle over the Riemann surface, joint with an auxiliar vector field, so-called Higgs field. This theory started around thirty years ago, with Hitchin's work, when he reduced the self-duality equations from dimension four to dimension two, and so, studied those equations over Riemann surfaces. Hitchin baptized those fields as "Higgs fields" beacuse in the context of physics and ...

Dryout power of a CANFLEX bundle string with raised bearing pads

International Nuclear Information System (INIS)

Leung, L.K.H.; Dimmick, G.R.; Bullock, D.E.; Inch, W.W.R.; Jun, J.S.; Suk, H.C.

2001-01-01

Dryout power data have been obtained with CANFLEX bundle strings equipped with raised bearing pads (1.7 mm and 1.8 mm height as compared to 1.4 mm in the current Mk-IV design) at Stern Laboratories. The experiment covered a wide range of steam-water flow conditions in three flow tubes simulating uncrept, and 3.3% and 5.1% crept profiles. The dryout power follows consistent parametric trends: it increases with increasing mass-flow rate, and decreases with increasing pressure, inlet-fluid temperature and channel creep. Local and boiling-length-average (BLA) critical-heat-flux (CHF) values were evaluated from the dryout-power measurements. The dryout power and BLA CHF values of the high bearing-pad bundles are higher than those of the low bearing-pad bundles at the same channel inlet flow conditions. On average, the dryout powers for bundles with 1.7 mm and 1.8 mm bearing pads are about 8% and 10%, respectively, higher than those for the bundle with 1.4 mm bearing pads. Compared to the 37-element bundle, an enhancement in dryout power is shown with CANFLEX bundles for all bearing-pad heights, at flow conditions of interest for reactor licensing. The average dryout power enhancement varies from 4% for the CANFLEX bundle with 1.4 mm bearing pads in the uncrept channel to 27% for the CANFLEX bundle with 1.8 mm bearing pads in the 5.1% crept channel. (author)

Preliminary Analysis of the Fuel Bundle Stiffness by ANSYS for SFR

Energy Technology Data Exchange (ETDEWEB)

Lee, Byoung Oon; Cheon, Jin Sik; Hahn, Do Hee; Lee, Chan Bock [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2008-05-15

In SFR (Sodium-cooled Fast Reactor) the temperature of the fuel pin is higher than that of the hexagonal duct, so the thermal expansion rate of the fuel bundle is higher than that of the duct. The neutron fluence and the fuel pin pressure are also increased according to the burnup. So the radial expansion and bowing of a fuel pin bundle would occur, and then fuel bundle would interact with a duct. This phenomenon is called bundle-to-duct interaction (BDI). Under the BDI condition, excess cladding strain and hot spots would occur. Therefore BDI as well as the core mechanics should be considered to evaluate the FBR fuel integrity. The analysis codes such as ETOILE, SHADOW, and MARSE, have been developed to evaluate the BDI behavior. The ANSYS based model is also being developed to analysis the bundle duct interaction for SFR in Korea. In this paper, the fuel pin/bundle model for analyzing the bending deflection and oval deformation was described. The preliminary analysis of the fuel bundle stiffness was performed by the developed model.

The nucleoporin MEL-28 promotes RanGTP-dependent γ-tubulin recruitment and microtubule nucleation in mitotic spindle formation.

Science.gov (United States)

Yokoyama, Hideki; Koch, Birgit; Walczak, Rudolf; Ciray-Duygu, Fulya; González-Sánchez, Juan Carlos; Devos, Damien P; Mattaj, Iain W; Gruss, Oliver J

2014-01-01

The GTP-bound form of the Ran GTPase (RanGTP), produced around chromosomes, drives nuclear envelope and nuclear pore complex (NPC) re-assembly after mitosis. The nucleoporin MEL-28/ELYS binds chromatin in a RanGTP-regulated manner and acts to seed NPC assembly. Here we show that, upon mitotic NPC disassembly, MEL-28 dissociates from chromatin and re-localizes to spindle microtubules and kinetochores. MEL-28 directly binds microtubules in a RanGTP-regulated way via its C-terminal chromatin-binding domain. Using Xenopus egg extracts, we demonstrate that MEL-28 is essential for RanGTP-dependent microtubule nucleation and spindle assembly, independent of its function in NPC assembly. Specifically, MEL-28 interacts with the γ-tubulin ring complex and recruits it to microtubule nucleation sites. Our data identify MEL-28 as a RanGTP target that functions throughout the cell cycle. Its cell cycle-dependent binding to chromatin or microtubules discriminates MEL-28 functions in interphase and mitosis, and ensures that spindle assembly occurs only after NPC breakdown.

Deformation quantization with separation of variables of an endomorphism bundle

OpenAIRE

Karabegov, Alexander

2013-01-01

Given a holomorphic Hermitian vector bundle and a star-product with separation of variables on a pseudo-Kaehler manifold, we construct a star product on the sections of the endomorphism bundle of the dual bundle which also has the appropriately generalized property of separation of variables. For this star product we prove a generalization of Gammelgaard's graph-theoretic formula.

Rhinanthus serotinus (Schönheit) Oborny (Scrophulariaceae): immunohistochemical and ultrastructural studies of endosperm chalazal haustorium development.

Science.gov (United States)

Świerczyńska, Joanna; Kozieradzka-Kiszkurno, Małgorzata; Bohdanowicz, Jerzy

2013-12-01

Chalazal endosperm haustorium in Rhinanthus serotinus consists of a single large binucleate cell. It originates from the primary endosperm cell dividing transversely into two unequal cells: a smaller micropylar cell and a larger chalazal cell. The chalazal cell undergoes a single mitotic division, then lengthens significantly during development and functions as a chalazal endosperm haustorium. In this paper, immunofluorescent techniques, rhodamine phalloidin assay, and electron microscopy were used to examine the actin and tubulin cytoskeleton during the development of the chalazal haustorium. During the differentiation stage, numerous longitudinally oriented bundles of microfilaments ran along the axis of transvacuolar strands in haustorium. Microtubules formed intensely fluorescent areas near the nuclear envelope and also formed radial perinuclear microtubule arrays. In the fully differentiated haustorium cell, the actin cytoskeleton formed dense clusters of microfilaments on the chalazal and micropylar poles of the haustorium. Numerous microfilament bundles occurred near wall ingrowths on the chalazal wall. There were numerous clusters of microfilaments and microtubules around the huge lobed polytenic haustorial nuclei. The microfilaments were oriented longitudinally to the long axis of the haustorium cell and surrounded both nuclei. The microtubules formed radial perinuclear systems which were appeared to radiate from the surface of the nuclear envelope. The early stage of degeneration of the chalazal haustorium was accompanied by the degradation of microtubules and disruption of the parallel orientation of microtubules in the chalazal area of the cell. The degree of vacuolization increased, autophagous vacuoles appeared and the number of vesicles decreased.

The role of complementarity and partner brand price level in new product introduction strategy using bundle offers: A study on the quality perception of bundle components.

OpenAIRE

Khandeparkar, Kapil

2014-01-01

New products are often bundled with strong brands as an introduction strategy. This study helps to understand the scenarios which will be most beneficial to both the products in the bundle. The enhancement effect and categorisation theory is used to explain that the new product's quality perception is higher when it is bundled with a strong brand of a higher price and this effect is moderated by the complementarity of the bundled components. Also, the quality perception of the strong brand is...

Principal bundles the classical case

CERN Document Server

Sontz, Stephen Bruce

2015-01-01

This introductory graduate level text provides a relatively quick path to a special topic in classical differential geometry: principal bundles.  While the topic of principal bundles in differential geometry has become classic, even standard, material in the modern graduate mathematics curriculum, the unique approach taken in this text presents the material in a way that is intuitive for both students of mathematics and of physics. The goal of this book is to present important, modern geometric ideas in a form readily accessible to students and researchers in both the physics and mathematics communities, providing each with an understanding and appreciation of the language and ideas of the other.

Development of CANDU advanced fuel bundle

International Nuclear Information System (INIS)

Suk, H. C.; Hwang, W.; Rhee, B. W.; Jung, S. H.; Chung, C. H.

1992-05-01

This research project is underway in cooperation with AECL to develop the CANDU advanced fuel bundle (so-called, CANFLEX) which can enhance reactor safety and fuel economy in comparison with the current CANDU fuel and which can be used with natural uranium, slightly enriched uranium and other advanced fuel cycle. As the final schedule, the advanced fuel will be verified by carrying out a large scale demonstration of the bundle irradiation in a commercial CANDU reactor for 1996 and 1997, and consequently will be used in the existing and future CANDU reactors in Korea. The research activities during this year include the detail design of CANFLEX fuel with natural enriched uranium (CANFLEX-NU). Based on this design, CANFLEX fuel was mocked up. Out-of-pile hydraulic scoping tests were conducted with the fuel in the CANDU Cold Test Loop to investigate the condition under which maximum pressure drop occurs and the maximum value of the bundle pressure drop. (Author)

The C*-algebra of a vector bundle and fields of Cuntz algebras

OpenAIRE

Vasselli, Ezio

2004-01-01

We study the Pimsner algebra associated with the module of continuous sections of a Hilbert bundle, and prove that it is a continuous bundle of Cuntz algebras. We discuss the role of such Pimsner algebras w.r.t. the notion of inner endomorphism. Furthermore, we study bundles of Cuntz algebras carrying a global circle action, and assign to them a class in the representable KK-group of the zero-grade bundle. We compute such class for the Pimsner algebra of a vector bundle.

The differential geometry of higher order jets and tangent bundles

International Nuclear Information System (INIS)

De Leon, M.; Rodrigues, P.R.

1985-01-01

This chapter is devoted to the study of basic geometrical notions required for the development of the main object of the text. Some facts about Jet theory are reviewed. A particular case of Jet manifolds is considered: the tangent bundle of higher order. It is shown that this jet bundle possesses in a canonical way a certain kind of geometric structure, the so called almost tangent structure of higher order, and which is a generalization of the almost tangent geometry of the tangent bundle. Another important fact examined is the extension of the notion of 'spray' to higher order tangent bundles. (Auth.)

Modelling anisotropic covariance using stochastic development and sub-Riemannian frame bundle geometry

DEFF Research Database (Denmark)

Sommer, Stefan Horst; Svane, Anne Marie

2017-01-01

distributions. We discuss a factorization of the frame bundle projection map through this bundle, the natural sub-Riemannian structure of the frame bundle, the effect of holonomy, and the existence of subbundles where the Hormander condition is satisfied such that the Brownian motions have smooth transition......We discuss the geometric foundation behind the use of stochastic processes in the frame bundle of a smooth manifold to build stochastic models with applications in statistical analysis of non-linear data. The transition densities for the projection to the manifold of Brownian motions developed...... in the frame bundle lead to a family of probability distributions on the manifold. We explain how data mean and covariance can be interpreted as points in the frame bundle or, more precisely, in the bundle of symmetric positive definite 2-tensors analogously to the parameters describing Euclidean normal...

Bundles of Norms About Teen Sex and Pregnancy.

Science.gov (United States)

Mollborn, Stefanie; Sennott, Christie

2015-09-01

Teen pregnancy is a cultural battleground in struggles over morality, education, and family. At its heart are norms about teen sex, contraception, pregnancy, and abortion. Analyzing 57 interviews with college students, we found that "bundles" of related norms shaped the messages teens hear. Teens did not think their communities encouraged teen sex or pregnancy, but normative messages differed greatly, with either moral or practical rationalizations. Teens readily identified multiple norms intended to regulate teen sex, contraception, abortion, childbearing, and the sanctioning of teen parents. Beyond influencing teens' behavior, norms shaped teenagers' public portrayals and post hoc justifications of their behavior. Although norm bundles are complex to measure, participants could summarize them succinctly. These bundles and their conflicting behavioral prescriptions create space for human agency in negotiating normative pressures. The norm bundles concept has implications for teen pregnancy prevention policies and can help revitalize social norms for understanding health behaviors. © The Author(s) 2014.

Development and Assessment of a Bundle Correction Method for CHF

International Nuclear Information System (INIS)

Hwang, Dae Hyun; Chang, Soon Heung

1993-01-01

A bundle correction method, based on the conservation laws of mass, energy, and momentum in an open subchannel, is proposed for the prediction of the critical heat flux (CHF) in rod bundles from round tube CHF correlations without detailed subchannel analysis. It takes into account the effects of the enthalpy and mass velocity distributions at subchannel level using the first dericatives of CHF with respect to the independent parameters. Three different CHF correlations for tubes (Groeneveld's CHF table, Katto correlation, and Biasi correlation) have been examined with uniformly heated bundle CHF data collected from various sources. A limited number of GHE data from a non-uniformly heated rod bundle are also evaluated with the aid of Tong's F-factor. The proposed method shows satisfactory CHF predictions for rod bundles both uniform and non-uniform power distributions. (Author)

Development of nuclear fuel. Development of CANDU advanced fuel bundle

International Nuclear Information System (INIS)

Suk, Ho Chun; Hwang, Woan; Jeong, Young Hwan; Jung, Sung Hoon

1991-07-01

In order to develop CANDU advanced fuel, the agreement of the joint research between KAERI and AECL was made on February 19, 1991. AECL conceptual design of CANFLEX bundle for Bruce reactors was analyzed and then the reference design and design drawing of the advanced fuel bundle with natural uranium fuel for CANDU-6 reactor were completed. The CANFLEX fuel cladding was preliminarily investigated. The fabricability of the advanced fuel bundle was investigated. The design and purchase of the machinery tools for the bundle fabrication for hydraulic scoping tests were performed. As a result of CANFLEX tube examination, the tubes were found to be meet the criteria proposed in the technical specification. The dummy bundles for hydraulic scoping tests have been fabricated by using the process and tools, where the process parameters and tools have been newly established. (Author)

Tubular lysosome morphology and distribution within macrophages depend on the integrity of cytoplasmic microtubules

International Nuclear Information System (INIS)

Swanson, J.; Bushnell, A.; Silverstein, S.C.

1987-01-01

Pinocytosis of the fluorescent dye lucifer yellow labels elongated, membrane-bound tubular organelles in several cell types, including cultured human monocytes, thioglycolate-elicited mouse peritoneal macrophages, and the macrophage-like cell line J774.2. These tubular structures can be identified as lysosomes by acid phosphatase histochemistry and immunofluorescence localization of cathepsin L. The abundance of tubular lysosomes is markedly increased by treatment with phorbol 12-myristate 13-acetate. When labeled by pinocytosis of microperoxidase and examined by electron microscopic histochemistry, the tubular lysosomes have an outside diameter of ≅ 75 nm and a length of several micrometers; they radiate from the cell's centrosphere in alignment with cytoplasmic microtubules and intermediate filaments. Incubation of phorbol myristate acetate-treated macrophages at 4 0 C or in medium containing 5 μM colchicine or nocodazole at 37 0 C leads to disassembly of microtubules and fragmentation of the tubular lysosomes. Return of the cultures to 37 0 C or removal of nocodazole from the medium leads to reassembly of microtubules and the reappearance of tubular lysosomes within 10-20 min. The authors conclude that microtubules are essential for the maintenance of tubular lysosome morphology and that, in macrophages, a significant proportion of the lysosomal compartment is contained within these tubular structures

An antitubulin agent BCFMT inhibits proliferation of cancer cells and induces cell death by inhibiting microtubule dynamics.

Directory of Open Access Journals (Sweden)

Ankit Rai

Full Text Available Using cell based screening assay, we identified a novel anti-tubulin agent (Z-5-((5-(4-bromo-3-chlorophenylfuran-2-ylmethylene-2-thioxothiazolidin-4-one (BCFMT that inhibited proliferation of human cervical carcinoma (HeLa (IC(50, 7.2 ± 1.8 µM, human breast adenocarcinoma (MCF-7 (IC(50, 10.0 ± 0.5 µM, highly metastatic breast adenocarcinoma (MDA-MB-231 (IC(50, 6.0 ± 1 µM, cisplatin-resistant human ovarian carcinoma (A2780-cis (IC(50, 5.8 ± 0.3 µM and multi-drug resistant mouse mammary tumor (EMT6/AR1 (IC(50, 6.5 ± 1 µM cells. Using several complimentary strategies, BCFMT was found to inhibit cancer cell proliferation at G2/M phase of the cell cycle apparently by targeting microtubules. In addition, BCFMT strongly suppressed the dynamics of individual microtubules in live MCF-7 cells. At its half maximal proliferation inhibitory concentration (10 µM, BCFMT reduced the rates of growing and shortening phases of microtubules in MCF-7 cells by 37 and 40%, respectively. Further, it increased the time microtubules spent in the pause (neither growing nor shortening detectably state by 135% and reduced the dynamicity (dimer exchange per unit time of microtubules by 70%. In vitro, BCFMT bound to tubulin with a dissociation constant of 8.3 ± 1.8 µM, inhibited tubulin assembly and suppressed GTPase activity of microtubules. BCFMT competitively inhibited the binding of BODIPY FL-vinblastine to tubulin with an inhibitory concentration (K(i of 5.2 ± 1.5 µM suggesting that it binds to tubulin at the vinblastine site. In cultured cells, BCFMT-treatment depolymerized interphase microtubules, perturbed the spindle organization and accumulated checkpoint proteins (BubR1 and Mad2 at the kinetochores. BCFMT-treated MCF-7 cells showed enhanced nuclear accumulation of p53 and its downstream p21, which consequently activated apoptosis in these cells. The results suggested that BCFMT inhibits proliferation of several types of cancer cells including drug

Auxin-dependent microtubule responses and seedling development are affected in a rice mutant resistant to EPC

International Nuclear Information System (INIS)

Nick, P.; Yatou, O.; Furuya, M.; Lambert, A.M.

1994-01-01

Mutants in rice (Oryza sativa L. cv. japonica) were used to study the role of the cytoskeleton in signal-dependent morphogenesis. Mutants obtained by gamma ray irradiation were selected that failed to show inhibition of coleoptile elongation by the anti microtubular drug ethyl-N-phenylcarbamate (EPC). The mutation EPC-Resistant 31 (ER31), isolated from such a screen, caused lethality in putatively homozygous embryos. Heterozygotes exhibited drug resistance, impaired development of crown roots, and characteristic changes in the pattern of cell elongation: cell elongation was enhanced in mesocotyls and leaf sheaths, but inhibited in coleoptiles. The orientation of cortical microtubules changed correspondingly: for etiolated seedlings, compared with the wild-type, they were more transverse with respect to the long cell axis in mesocotyls and leaf sheaths, but more longitudinal in coleoptiles. In mutant coleoptiles, in contrast to wild-type, microtubules did not reorient in response to auxin, and their response to microtubule-eliminating and microtubule-stabilizing drugs was conspicuously reduced. In contrast, they responded normally to other stimuli such as gibberellins or red light. Auxin sensitivity as assayed by the dose-response for callus induction did not show any significant differences between wild-type and mutant. The mutant phenotype is interpreted in terms of an interrupted link between auxin-triggered signal transduction and microtubule reorientation. (author)

Emerging microtubule targets in glioma therapy

Czech Academy of Sciences Publication Activity Database

Katsetos, C.D.; Reginato, M.J.; Baas, P.W.; D'Agostino, L.; Legido, A.; Tuszynski, J. A.; Dráberová, Eduarda; Dráber, Pavel

2015-01-01

Roč. 22, č. 1 (2015), s. 49-72 ISSN 1071-9091 R&D Projects: GA MŠk LH12050; GA MZd NT14467 Grant - others:GA AV ČR M200521203PIPP; NIH(US) R01 NS028785; Philadelphia Health Education Corporation (PHEC)–St. Christopher’s Hospital for Children Reunified Endowment (C.D.K.)(US) 323256 Institutional support: RVO:68378050 Keywords : glioma tumorigenesis * glioblastoma * tubulin * microtubules Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.303, year: 2015

Discharge Burnup Evaluation of Natural Uranium Loaded CANFLEX-43 Fuel Bundle

International Nuclear Information System (INIS)

Roh, Gyu Hong; Kim, Yong Hee; Kim, Won Young; Park, Joo Hwan

2009-11-01

Using WIMS-AECL code, which is 2-dimensional lattice core used in CANDU physics calculation, the discharge burnup of the natural uranium loaded CANFLEX-43 fuel bundle was evaluated by comparing the discharge burnup of standard 37 element fuel bundle. When the discharge burnup of the standard 37 element fuel is 7,200 MWd/MTU, that of the CANFLEX 43 fuel bundle was evaluated as 7,077 MWd/MTU, by applying the same lattice conditions for both fuel bundles

Histones bundle F-actin filaments and affect actin structure.

Directory of Open Access Journals (Sweden)

Edna Blotnick

Full Text Available Histones are small polycationic proteins complexed with DNA located in the cell nucleus. Upon apoptosis they are secreted from the cells and react with extracellular polyanionic compounds. Actin which is a polyanionic protein, is also secreted from necrotic cells and interacts with histones. We showed that both histone mixture (histone type III and the recombinant H2A histone bundles F-actin, increases the viscosity of the F-actin containing solution and polymerizes G-actin. The histone-actin bundles are relatively insensitive to increase of ionic strength, unlike other polycation, histatin, lysozyme, spermine and LL-37 induced F-actin bundles. The histone-actin bundles dissociate completely only in the presence of 300-400 mM NaCl. DNA, which competes with F-actin for histones, disassembles histone induced actin bundles. DNase1, which depolymerizes F- to G-actin, actively unbundles the H2A histone induced but slightly affects the histone mixture induced actin bundles. Cofilin decreases the amount of F-actin sedimented by low speed centrifugation, increases light scattering and viscosity of F-actin-histone mixture containing solutions and forms star like superstructures by copolymerizing G-actin with H2A histone. The results indicate that histones are tightly attached to F-actin by strong electrostatic and hydrophobic forces. Since both histones and F-actin are present in the sputum of patients with cystic fibrosis, therefore, the formation of the stable histone-actin bundles can contribute to the pathology of this disease by increasing the viscosity of the sputum. The actin-histone interaction in the nucleus might affect gene expression.

Deformation quantization with separation of variables of an endomorphism bundle

Science.gov (United States)

Karabegov, Alexander

2014-01-01

Given a holomorphic Hermitian vector bundle E and a star-product with separation of variables on a pseudo-Kähler manifold, we construct a star product on the sections of the endomorphism bundle of the dual bundle E∗ which also has the appropriately generalized property of separation of variables. For this star product we prove a generalization of Gammelgaard's graph-theoretic formula.

Katanin localization requires triplet microtubules in Chlamydomonas reinhardtii.

Directory of Open Access Journals (Sweden)

Jessica M Esparza

Full Text Available Centrioles and basal bodies are essential for a variety of cellular processes that include the recruitment of proteins to these structures for both centrosomal and ciliary function. This recruitment is compromised when centriole/basal body assembly is defective. Mutations that cause basal body assembly defects confer supersensitivity to Taxol. These include bld2, bld10, bld12, uni3, vfl1, vfl2, and vfl3. Flagellar motility mutants do not confer sensitivity with the exception of mutations in the p60 (pf19 and p80 (pf15 subunits of the microtubule severing protein katanin. We have identified additional pf15 and bld2 (ε-tubulin alleles in screens for Taxol sensitivity. Null pf15 and bld2 alleles are viable and are not essential genes in Chlamydomonas. Analysis of double mutant strains with the pf15-3 and bld2-6 null alleles suggests that basal bodies in Chlamydomonas may recruit additional proteins beyond katanin that affect spindle microtubule stability. The bld2-5 allele is a hypomorphic allele and its phenotype is modulated by nutritional cues. Basal bodies in bld2-5 cells are missing proximal ends. The basal body mutants show aberrant localization of an epitope-tagged p80 subunit of katanin. Unlike IFT proteins, katanin p80 does not localize to the transition fibers of the basal bodies based on an analysis of the uni1 mutant as well as the lack of colocalization of katanin p80 with IFT74. We suggest that the triplet microtubules are likely to play a key role in katanin p80 recruitment to the basal body of Chlamydomonas rather than the transition fibers that are needed for IFT localization.

The proteasome of the differently-diverged eukaryote Giardia lamblia and its role in remodeling of the microtubule-based cytoskeleton.

Science.gov (United States)

Ray, Atrayee; Sarkar, Srimonti

2017-08-01

Giardia lamblia is the causative agent of the diarrheal disease giardiasis, against which only a limited number of drugs are currently available. Increasing reports of resistance to these drugs makes it necessary to identify new cellular targets for designing the next generation of anti-giardial drugs. Towards this goal, therapeutic agents that target the parasitic cellular machinery involved in the functioning of the unique microtubule-based cytoskeleton of the Giardia trophozoites are likely to be effective as microtubule function is not only important for the survival of trophozoites within the host, but also their extensive remodeling is necessary during the transition from trophozoites to cysts. Thus, drugs that affect microtubule remodeling have the potential to not only kill the disease-causing trophozoites, but also inhibit transmission of cysts in the community. Recent studies in other model organisms have indicated that the proteasome plays an integral role in the formation and remodeling of the microtubule-based cytoskeleton. This review draws attention to the various processes by which the giardial proteasome may impact the functioning of its microtubule cytoskeleton and highlights the possible differences of the parasitic proteasome and some of other cellular machinery involved in microtubule remodeling, compared to that of the higher eukaryotic host.

Analytic convergence of harmonic metrics for parabolic Higgs bundles

Science.gov (United States)

Kim, Semin; Wilkin, Graeme

2018-04-01

In this paper we investigate the moduli space of parabolic Higgs bundles over a punctured Riemann surface with varying weights at the punctures. We show that the harmonic metric depends analytically on the weights and the stable Higgs bundle. This gives a Higgs bundle generalisation of a theorem of McOwen on the existence of hyperbolic cone metrics on a punctured surface within a given conformal class, and a generalisation of a theorem of Judge on the analytic parametrisation of these metrics.

Characteristics of liquid and boiling sodium flows in heating pin bundles

International Nuclear Information System (INIS)

Menant, Bernard

1976-01-01

This study is related to cooling accidents which could occur in sodium cooled fast reactors. Thermo-hydraulic aspects of boiling experiments in pin bundles with helical wire-wrap spacer systems, in the case of undamaged geometries, are analyzed. Differences and analogies in the behavior of multi-rod bundle flows and one-dimensional channel flows are studied. A boiling model is developed for bundle geometries, and predictions obtained with the FLICA code using this models are presented. These predictions are compared with experimental results obtained in a water 19-rod bundle. Then, results of sodium boiling experiments through a 19-rod bundle are interpreted. Both cases of high power and reduced power are envisaged. (author) [fr

Effective thermal conductivity of a heat generating rod bundle dissipating heat by natural convection and radiation

International Nuclear Information System (INIS)

Senve, Vinay; Narasimham, G.S.V.L.

2011-01-01

Highlights: → Transport processes in isothermal hexagonal sheath with 19 heat generating rods is studied. → Correlation is given to predict the maximum temperature considering all transport processes. → Effective thermal conductivity of rod bundle can be obtained using max temperature. → Data on the critical Rayleigh numbers for p/d ratios of 1.1-2.0 is presented. → Radiative heat transfer contributes to heat dissipation of 38-65% of total heat. - Abstract: A numerical study of conjugate natural convection and surface radiation in a horizontal hexagonal sheath housing 19 solid heat generating rods with cladding and argon as the fill gas, is performed. The natural convection in the sheath is driven by the volumetric heat generation in the solid rods. The problem is solved using the FLUENT CFD code. A correlation is obtained to predict the maximum temperature in the rod bundle for different pitch-to-diameter ratios and heat generating rates. The effective thermal conductivity is related to the heat generation rate, maximum temperature and the sheath temperature. Results are presented for the dimensionless maximum temperature, Rayleigh number and the contribution of radiation with changing emissivity, total wattage and the pitch-to-diameter ratio. In the simulation of a larger system that contains a rod bundle, the effective thermal conductivity facilitates simplified modelling of the rod bundle by treating it as a solid of effective thermal conductivity. The parametric studies revealed that the contribution of radiation can be 38-65% of the total heat generation, for the parameter ranges chosen. Data for critical Rayleigh number above which natural convection comes into effect is also presented.

Endoplasmic-reticulum-mediated microtubule alignment governs cytoplasmic streaming.

Science.gov (United States)

Kimura, Kenji; Mamane, Alexandre; Sasaki, Tohru; Sato, Kohta; Takagi, Jun; Niwayama, Ritsuya; Hufnagel, Lars; Shimamoto, Yuta; Joanny, Jean-François; Uchida, Seiichi; Kimura, Akatsuki

2017-04-01

Cytoplasmic streaming refers to a collective movement of cytoplasm observed in many cell types. The mechanism of meiotic cytoplasmic streaming (MeiCS) in Caenorhabditis elegans zygotes is puzzling as the direction of the flow is not predefined by cell polarity and occasionally reverses. Here, we demonstrate that the endoplasmic reticulum (ER) network structure is required for the collective flow. Using a combination of RNAi, microscopy and image processing of C. elegans zygotes, we devise a theoretical model, which reproduces and predicts the emergence and reversal of the flow. We propose a positive-feedback mechanism, where a local flow generated along a microtubule is transmitted to neighbouring regions through the ER. This, in turn, aligns microtubules over a broader area to self-organize the collective flow. The proposed model could be applicable to various cytoplasmic streaming phenomena in the absence of predefined polarity. The increased mobility of cortical granules by MeiCS correlates with the efficient exocytosis of the granules to protect the zygotes from osmotic and mechanical stresses.

Interactive hypermedia training manual for spent-fuel bundle counters

International Nuclear Information System (INIS)

Basso, R.A.

1990-07-01

Spent-fuel bundle counters, developed by the Canadian Safeguards Support Program for the International Atomic Energy Agency, provide a secure and independent means of counting the number of irradiated fuel bundles discharged into the fuel storage bays at CANDU nuclear power stations. Paper manuals have been traditionally used to familiarize IAEA inspectors with the operation, maintenance and extensive reporting capabilities of the bundle counters. To further assist inspectors, an interactive training manual has been developed on an Apple Macintosh computer using hypermedia software. The manual uses interactive animation and sound, in conjunction with the traditional text and graphics, to simulate the underlying operation and logic of the bundle counters. This paper presents the key features of the interactive manual and highlights the advantages of this new technology for training

Neuronal microtubule organization: from minus end to plus end

NARCIS (Netherlands)

Yau, K.W.

2016-01-01

Neurons are highly polarized cells consisting of a dendritic part and axonal part. Dendrites receive signals from other cells while axons transmit signals to other cells. In this thesis, mostly hippocampal neurons from rat embryos are used to study fundamental aspects of the microtubule organization

SCADOP: Phenomenological modeling of dryout in nuclear fuel rod bundles

Energy Technology Data Exchange (ETDEWEB)

Dasgupta, Arnab, E-mail: arnie@barc.gov.in; Chandraker, D.K., E-mail: dineshkc@barc.gov.in; Vijayan, P.K., E-mail: vijayanp@barc.gov.in

2015-11-15

Highlights: • Phenomenological model for annular flow dryout is presented. • The model evaluates initial entrained fraction using a new methodology. • The history effect in annular flow is predicted and validated. • Rod bundle dryout is predicted using subchannel methodology. • Model is validated against experimental dryout data in tubes and rod bundles. - Abstract: Analysis and prediction of dryout is of important consequence to safety of nuclear fuel clusters of boiling water type of reactors. Traditionally, experimental correlations are used for dryout predictions. Since these correlations are based on operating parameters and do not aim to model the underlying phenomena, there has been a proliferation of the correlations, each catering to some specific bundle geometry under a specific set of operating conditions. Moreover, such experiments are extremely costly. In general, changes in tested bundle geometry for improvement in thermal-hydraulic performance would require re-experimentation. Understanding and modeling the basic processes leading to dryout in flow boiling thus has great incentive. Such a model has the ability to predict dryout in any rod bundle geometry, unlike the operating parameter based correlation approach. Thus more informed experiments can be carried out. A good model can, reduce the number of experiments required during the iterations in bundle design. In this paper, a phenomenological model as indicated above is presented. The model incorporates a new methodology to estimate the Initial Entrained Fraction (IEF), i.e., entrained fraction at the onset of annular flow. The incorporation of this new methodology is important since IEF is often assumed ad-hoc and sometimes also used as a parameter to tune the model predictions to experimental data. It is highlighted that IEF may be low under certain conditions against the general perception of a high IEF due to influence of churn flow. It is shown that the same phenomenological model is

C-terminal region of MAP7 domain containing protein 3 (MAP7D3 promotes microtubule polymerization by binding at the C-terminal tail of tubulin.

Directory of Open Access Journals (Sweden)

Saroj Yadav

Full Text Available MAP7 domain containing protein 3 (MAP7D3, a newly identified microtubule associated protein, has been shown to promote microtubule assembly and stability. Its microtubule binding region has been reported to consist of two coiled coil motifs located at the N-terminus. It possesses a MAP7 domain near the C-terminus and belongs to the microtubule associated protein 7 (MAP7 family. The MAP7 domain of MAP7 protein has been shown to bind to kinesin-1; however, the role of MAP7 domain in MAP7D3 remains unknown. Based on the bioinformatics analysis of MAP7D3, we hypothesized that the MAP7 domain of MAP7D3 may have microtubule binding activity. Indeed, we found that MAP7 domain of MAP7D3 bound to microtubules as well as enhanced the assembly of microtubules in vitro. Interestingly, a longer fragment MDCT that contained the MAP7 domain (MD with the C-terminal tail (CT of the protein promoted microtubule polymerization to a greater extent than MD and CT individually. MDCT stabilized microtubules against dilution induced disassembly. MDCT bound to reconstituted microtubules with an apparent dissociation constant of 3.0 ± 0.5 µM. An immunostaining experiment showed that MDCT localized along the length of the preassembled microtubules. Competition experiments with tau indicated that MDCT shares its binding site on microtubules with tau. Further, we present evidence indicating that MDCT binds to the C-terminal tail of tubulin. In addition, MDCT could bind to tubulin in HeLa cell extract. Here, we report a microtubule binding region in the C-terminal region of MAP7D3 that may have a role in regulating microtubule assembly dynamics.

Application of quasi-steady state methods to molecular motor transport on microtubules in fungal hyphae.

Science.gov (United States)

Dauvergne, Duncan; Edelstein-Keshet, Leah

2015-08-21

We consider bidirectional transport of cargo by molecular motors dynein and kinesin that walk along microtubules, and/or diffuse in the cell. The motors compete to transport cargo in opposite directions with respect to microtubule polarity (towards the plus or minus end of the microtubule). In recent work, Gou et al. (2014) used a hierarchical set of models, each consisting of continuum transport equations to track the evolution of motors and their cargo (early endosomes) in the specific case of the fungus Ustilago maydis. We complement their work using a framework of quasi-steady state analysis developed by Newby and Bressloff (2010) and Bressloff and Newby (2013) to reduce the models to an approximating steady state Fokker-Plank equation. This analysis allows us to find analytic approximations to the steady state solutions in many cases where the full models are not easily solved. Consequently, we can make predictions about parameter dependence of the resulting spatial distributions. We also characterize the overall rates of bulk transport and diffusion, and how these are related to state transition parameters, motor speeds, microtubule polarity distribution, and specific assumptions made. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

NARCIS (Netherlands)

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

Moduli of Parabolic Higgs Bundles and Atiyah Algebroids

DEFF Research Database (Denmark)

Logares, Marina; Martens, Johan

2010-01-01

In this paper we study the geometry of the moduli space of (non-strongly) parabolic Higgs bundles over a Riemann surface with marked points. We show that this space possesses a Poisson structure, extending the one on the dual of an Atiyah algebroid over the moduli space of parabolic vector bundle...

Fast breeder fuel pin bundle tests in the KNK II-reactor

International Nuclear Information System (INIS)

Haefner, H.E.; Bojarsky, E.

1986-11-01

Three variants of ring elements with test bundles will be reported in this paper: In a first step a ring element was built with a permanently integrated test bundle (19 carbide pins of the Karlsruhe reference concept) while the proven fuel element components have been largely maintained. This irradiation will be completed in autumn 1986 after 380 full power days of operation. The central topic of this paper will be the technique of reloadable ring elements with replaceable test bundles. A first experiment, TOAST, is in preparation. For this experiment, above all the components of the fuel element head and foot had to be newly developed and tested. A special version of double-walled replaceable test bundles to be used in the TETRA temperature transient experiments will be briefly mentioned. It is envisaged in these experiments to vary in a defined manner the coolant flow at remotely assembled test bundles consisting of 19 KNK pins each having undergone a high burnup and to use a measuring and control plug placed on the test bundle so that a variety of fuel pin temperature programs can be realized. Finally, some additional aspects of bundle design will be indicated. (orig./GL) [de

Left bundle-branch block

DEFF Research Database (Denmark)

Risum, Niels; Strauss, David; Sogaard, Peter

2013-01-01

The relationship between myocardial electrical activation by electrocardiogram (ECG) and mechanical contraction by echocardiography in left bundle-branch block (LBBB) has never been clearly demonstrated. New strict criteria for LBBB based on a fundamental understanding of physiology have recently...

Spindle pole body-anchored Kar3 drives the nucleus along microtubules from another nucleus in preparation for nuclear fusion during yeast karyogamy.

Science.gov (United States)

Gibeaux, Romain; Politi, Antonio Z; Nédélec, François; Antony, Claude; Knop, Michael

2013-02-01

Nuclear migration during yeast karyogamy, termed nuclear congression, is required to initiate nuclear fusion. Congression involves a specific regulation of the microtubule minus end-directed kinesin-14 motor Kar3 and a rearrangement of the cytoplasmic microtubule attachment sites at the spindle pole bodies (SPBs). However, how these elements interact to produce the forces necessary for nuclear migration is less clear. We used electron tomography, molecular genetics, quantitative imaging, and first principles modeling to investigate how cytoplasmic microtubules are organized during nuclear congression. We found that Kar3, with the help of its light chain, Cik1, is anchored during mating to the SPB component Spc72 that also serves as a nucleator and anchor for microtubules via their minus ends. Moreover, we show that no direct microtubule-microtubule interactions are required for nuclear migration. Instead, SPB-anchored Kar3 exerts the necessary pulling forces laterally on microtubules emanating from the SPB of the mating partner nucleus. Therefore, a twofold symmetrical application of the core principle that drives nuclear migration in higher cells is used in yeast to drive nuclei toward each other before nuclear fusion.

On the existence of n-dimensional indecomposable vector bundles

International Nuclear Information System (INIS)

Tan Xiaojiang.

1991-09-01

Let X be an arbitrary smooth irreducible complex projective curve of genus g with g ≥ 4. In this paper we extend the existence theorem of special divisors to high dimensional indecomposable vector bundles. We give a necessary and sufficient condition on the existence of n-dimensional indecomposable vector bundles E with deg(E) = d, dimH 0 (X,E) ≥ h. We also determine under what condition the set of all such vector bundles will be finite and how many elements it contains. (author). 9 refs

Aerosol retention in the flooded steam generator bundle during SGTR

International Nuclear Information System (INIS)

Lind, Terttaliisa; Dehbi, Abdel; Guentay, Salih

2011-01-01

Research highlights: → High retention of aerosol particles in a steam generator bundle flooded with water. → Increasing particle inertia, i.e., particle size and velocity, increases retention. → Much higher retention of aerosol particles in the steam generator bundle flooded with water than in a dry bundle. → Much higher retention of aerosol particles in the steam generator bundle than in a bare pool. → Bare pool models have to be adapted to be applicable for flooded bundles. - Abstract: A steam generator tube rupture in a pressurized water reactor may cause accidental release of radioactive particles into the environment. Its specific significance is in its potential to bypass the containment thereby providing a direct pathway of the radioactivity from the primary circuit to the environment. Under certain severe accident scenarios, the steam generator bundle may be flooded with water. In addition, some severe accident management procedures are designed to minimize the release of radioactivity into the environment by flooding the defective steam generator secondary side with water when the steam generator has dried out. To extend our understanding of the particle retention phenomena in the flooded steam generator bundle, tests were conducted in the ARTIST and ARTIST II programs to determine the effect of different parameters on particle retention. The effects of particle type (spherical or agglomerate), particle size, gas mass flow rate, and the break submergence on particle retention were investigated. Results can be summarized as follows: increasing particle inertia was found to increase retention in the flooded bundle. Particle shape, i.e., agglomerate or spherical structure, did not affect retention significantly. Even with a very low submergence, 0.3 m above the tube break, significant aerosol retention took place underlining the importance of the jet-bundle interactions close to the tube break. Droplets were entrained from the water surface with

The plant microtubule-associated protein AtMAP65-3/PLE is essential for cytokinetic phragmoplast function.

Science.gov (United States)

Müller, Sabine; Smertenko, Andrei; Wagner, Vera; Heinrich, Maria; Hussey, Patrick J; Hauser, Marie-Theres

2004-03-09

Directional cell expansion in interphase and nuclear and cell division in M-phase are mediated by four microtubule arrays, three of which are unique to plants: the interphase array, the preprophase band, and the phragmoplast. The plant microtubule-associated protein MAP65 has been identified as a key structural component in these arrays. The Arabidopsis genome has nine MAP65 genes, and here we show that one, AtMAP65-3/PLE, locates only to the mitotic arrays and is essential for cytokinesis. The Arabidopsis pleiade (ple) alleles are single recessive mutations, and we show that these mutations are in the AtMAP65-3 gene. Moreover, these mutations cause C-terminal truncations that abolish microtubule binding. In the ple mutants the anaphase spindle is normal, and the cytokinetic phragmoplast can form but is distorted; not only is it wider, but the midline, the region where oppositely oriented microtubules overlap, is unusually expanded. Here we present data that demonstrate an essential role for AtMAP65-3/PLE in cytokinesis in plant cells.

16-rod-bundle: Irradiation in the MZFR and post-irradiation examinations

International Nuclear Information System (INIS)

Manzel, R.

1979-04-01

In the course of the irradiation of a 16-rod prototype bundle, the basis has been established for the irradiation of experimental fuel assemblies containing full-length PWR fuel rods in standard positions of the MZFR. The prototype bundle was discharged after an irradiation time of 284 full power days and a burnup of 11400 MWd/tU. The overall performance of the prototype bundle was highly satisfactory. Detailed post-irradiation examinations confirmed the good conditions of bundle structures and fuel rods. (orig.) [de

Modeling and analysis of thermal damping in heat exchanger tube bundles

Energy Technology Data Exchange (ETDEWEB)

Khushnood, Shahab, E-mail: seeshahab@yahoo.co [University of Engineering and Technology, Taxila (Pakistan); Khan, Zaffar Muhammad, E-mail: mafzmlk@hotmail.co [National University of Sciences and Technology, Rawalpindi (Pakistan); Malik, Muhammad Afzaal [National University of Sciences and Technology, Rawalpindi (Pakistan); Iqbal, Qamar, E-mail: qamarch@yahoo.co [University of Engineering and Technology, Taxila (Pakistan); Bashir, Sajid; Khan, Muddasar [University of Engineering and Technology, Taxila (Pakistan); Koreshi, Zafarullah, E-mail: zaffark@yahoo.co [Air University, Islamabad (Pakistan); Khan, Mahmood Anwar [National University of Sciences and Technology, Rawalpindi (Pakistan); Malik, Tahir Nadeem [University of Engineering and Technology, Taxila (Pakistan); Qureshi, Arshad Hussain [University of Engineering and Technology, Lahore (Pakistan)

2010-07-15

Most structures and equipment used in nuclear power plant and process plant, such as reactor internals, fuel rods, steam generator tubes bundles, and process heat exchanger tube bundles, are subjected to flow-induced vibrations (FIV). Costly plant shutdowns have been the source of motivation for continuing studies on cross-flow-induced vibration in these structures. Damping has been the target of various research attempts related to FIV in tube bundles. A recent research attempt has shown the usefulness of a phenomenon termed as 'thermal damping'. The current paper focuses on the modeling and analysis of thermal damping in tube bundles subjected to cross-flow. It is expected that the present attempt will help in establishing improved design guidelines with respect to damping in tube bundles.

Gas flow and thermal mixing in a helically wound tube bundle

International Nuclear Information System (INIS)

Chiger, H.D.

1980-07-01

The thermal dissipation of a hot gas streak flowing across a segment of a helically wound tube bundle and the bypass flow streaming between the tubes and the bundle wall were investigated experimentally in the range of 8000 < Re < 50,000. Two different modes of creating a hot streak were employed. A planar hot streak was (1) injected at the entrance to the tube bundle and (2) generated by electrically heating several tubes past the bundle inlet. In the first case the mixing occurs in a region of lower turbulence since it occurs near the bundle inlet. In the second case the mixing occurs in a region of higher turbulence since the flow has already passed over several tube rows before the hot streak is generated

A compressed sensing approach for resolution improvement in fiber-bundle based endomicroscopy

Science.gov (United States)

Dumas, John P.; Lodhi, Muhammad A.; Bajwa, Waheed U.; Pierce, Mark C.

2018-02-01

Endomicroscopy techniques such as confocal, multi-photon, and wide-field imaging have all been demonstrated using coherent fiber-optic imaging bundles. While the narrow diameter and flexibility of fiber bundles is clinically advantageous, the number of resolvable points in an image is conventionally limited to the number of individual fibers within the bundle. We are introducing concepts from the compressed sensing (CS) field to fiber bundle based endomicroscopy, to allow images to be recovered with more resolvable points than fibers in the bundle. The distal face of the fiber bundle is treated as a low-resolution sensor with circular pixels (fibers) arranged in a hexagonal lattice. A spatial light modulator is located conjugate to the object and distal face, applying multiple high resolution masks to the intermediate image prior to propagation through the bundle. We acquire images of the proximal end of the bundle for each (known) mask pattern and then apply CS inversion algorithms to recover a single high-resolution image. We first developed a theoretical forward model describing image formation through the mask and fiber bundle. We then imaged objects through a rigid fiber bundle and demonstrate that our CS endomicroscopy architecture can recover intra-fiber details while filling inter-fiber regions with interpolation. Finally, we examine the relationship between reconstruction quality and the ratio of the number of mask elements to the number of fiber cores, finding that images could be generated with approximately 28,900 resolvable points for a 1,000 fiber region in our platform.

Large eddy simulation of bundle turbulent flows

International Nuclear Information System (INIS)

Hassan, Y.A.; Barsamian, H.R.

1995-01-01

Large eddy simulation may be defined as simulation of a turbulent flow in which the large scale motions are explicitly resolved while the small scale motions are modeled. This results into a system of equations that require closure models. The closure models relate the effects of the small scale motions onto the large scale motions. There have been several models developed, the most popular is the Smagorinsky eddy viscosity model. A new model has recently been introduced by Lee that modified the Smagorinsky model. Using both of the above mentioned closure models, two different geometric arrangements were used in the simulation of turbulent cross flow within rigid tube bundles. An inlined array simulations was performed for a deep bundle (10,816 nodes) as well as an inlet/outlet simulation (57,600 nodes). Comparisons were made to available experimental data. Flow visualization enabled the distinction of different characteristics within the flow such as jet switching effects in the wake of the bundle flow for the inlet/outlet simulation case, as well as within tube bundles. The results indicate that the large eddy simulation technique is capable of turbulence prediction and may be used as a viable engineering tool with the careful consideration of the subgrid scale model. (author)

Single and two-phase flow pressure drop for CANFLEX bundle

Energy Technology Data Exchange (ETDEWEB)

Park, Joo Hwan; Jun, Ji Su; Suk, Ho Chun [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of); Dimmick, G R; Bullock, D E [Atomic Energy of Canada Limited, Ontario (Canada)

1999-12-31

Friction factor and two-phase flow frictional multiplier for a CANFLEX bundle are newly developed and presented in this paper. CANFLEX as a 43-element fuel bundle has been developed jointly by AECL/KAERI to provide greater operational flexibility for CANDU reactor operators and designers. Friction factor and two-phase flow frictional multiplier have been developed by using the experimental data of pressure drops obtained from two series of Freon-134a (R-134a) CHF tests with a string of simulated CANFLEX bundles in a single phase and a two-phase flow conditions. The friction factor for a CANFLEX bundle is found to be about 20% higher than that of Blasius for a smooth circular pipe. The pressure drop predicted by using the new correlations of friction factor and two-phase frictional multiplier are well agreed with the experimental pressure drop data of CANFLEX bundle within {+-} 5% error. 11 refs., 5 figs. (Author)

Introduction to the theory of fiber bundles and connections I

International Nuclear Information System (INIS)

Socolvsky, M.

1990-01-01

In lectures 1 and 2 we discuss basic concepts of topology and differential geometry: definition of a topological space and of Hausdorff, compact, connected and paracompact spaces; topological groups and actions of groups on spaces; differentiable manifolds, tangent vectors and 1 forms; partitions of unity and Lie groups. In lecture 3 we present the concept of a fiber bundle and discuss vector bundles and principal bundles. The concept of a connection on a smooth vector bundle is defined in lecture 4, together with the associated concepts of curvature and parallel transport; as an illustration we present the Levi-Civita connection on a Riemannian manifold. Finally, in lecture 5 we define connections on principal bundles and present examples with the Lie groups U(1) and SU(2). For reasons of space the present article only includes lectures 1, 2 and 3. Lectures 4 and 5 will be published in a forthcoming paper. (Author)

Single and two-phase flow pressure drop for CANFLEX bundle

Energy Technology Data Exchange (ETDEWEB)

Park, Joo Hwan; Jun, Ji Su; Suk, Ho Chun [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of); Dimmick, G. R.; Bullock, D. E. [Atomic Energy of Canada Limited, Ontario (Canada)

1998-12-31

Friction factor and two-phase flow frictional multiplier for a CANFLEX bundle are newly developed and presented in this paper. CANFLEX as a 43-element fuel bundle has been developed jointly by AECL/KAERI to provide greater operational flexibility for CANDU reactor operators and designers. Friction factor and two-phase flow frictional multiplier have been developed by using the experimental data of pressure drops obtained from two series of Freon-134a (R-134a) CHF tests with a string of simulated CANFLEX bundles in a single phase and a two-phase flow conditions. The friction factor for a CANFLEX bundle is found to be about 20% higher than that of Blasius for a smooth circular pipe. The pressure drop predicted by using the new correlations of friction factor and two-phase frictional multiplier are well agreed with the experimental pressure drop data of CANFLEX bundle within {+-} 5% error. 11 refs., 5 figs. (Author)

Mutations in Human Tubulin Proximal to the Kinesin-Binding Site Alter Dynamic Instability at Microtubule Plus- and Minus-Ends

Energy Technology Data Exchange (ETDEWEB)

Ti, Shih-Chieh; Pamula, Melissa C.; Howes, Stuart C.; Duellberg, Christian; Cade, Nicholas I.; Kleiner, Ralph E.; Forth, Scott; Surrey, Thomas; Nogales, Eva; Kapoor, Tarun M.

2016-04-01

The assembly of microtubule-based cellular structures depends on regulated tubulin polymerization and directional transport. In this research, we have purified and characterized tubulin heterodimers that have human β-tubulin isotype III (TUBB3), as well as heterodimers with one of two β-tubulin mutations (D417H or R262H). Both point mutations are proximal to the kinesin-binding site and have been linked to an ocular motility disorder in humans. Compared to wild-type, microtubules with these mutations have decreased catastrophe frequencies and increased average lifetimes of plus- and minus-end-stabilizing caps. Importantly, the D417H mutation does not alter microtubule lattice structure or Mal3 binding to growing filaments. Instead, this mutation reduces the affinity of tubulin for TOG domains and colchicine, suggesting that the distribution of tubulin heterodimer conformations is changed. Together, our findings reveal how residues on the surface of microtubules, distal from the GTP-hydrolysis site and inter-subunit contacts, can alter polymerization dynamics at the plus- and minus-ends of microtubules.

Getting the Most from Your CD-ROM Dollars: The CD-ROM Bundle [and] The Pros and Cons of CD-ROM Bundling.

Science.gov (United States)

Sarjeant, Eric W.; O'Connor, Mary Ann

1992-01-01

Discusses and reviews CD-ROM bundles--i.e., hardware, software and CD-ROM kits--including their features, specifications, drawbacks, and prices. Recommends buying through mail order for the best selection and price. The pros and cons of bundling as a marketing strategy are discussed and a list of vendors is provided. (EA)

MYOCARDIAL DEFORMATION AND COMPLETE LEFT BUNDLE BRANCH BLOCK

Directory of Open Access Journals (Sweden)

E. N. Pavlyukova

2015-12-01

Full Text Available Tissue Doppler imaging is evolving as a useful echocardiographic tool for quantitative assessment of left ventricular systolic and diastolic function. Over the last 10 years, myocardial deformation imaging has become possible initially with tissue Doppler , and more recently with myocardial speckle-tracking using 2D echocardiography. Unlike simple tissue velocity measurements, deformation measurements are specific for the region of interest. Strain rate or strain measurements have been used as sensitive indicators for subclinical diseases, and it is the most widely used tool to assess mechanical dyssynchrony. Left bundle branch block is a frequent, etiologically heterogeneous, clinically hostile and diagnostically challenging entity. About 2% of patients underwent cardiac stress testing show stable or intermittent left bundle branch block. Presence of left bundle branch block is associated with a lower and slower diastolic coronary flow velocity especially during hyperemia. Stress echocardiography is the best option for the diagnosis of ischemic heart disease, albeit specificity and sensitivity reduce in patients with left bundle branch block in the territory of left anterior descending artery in presence of initial septum dyskinesia.

Absorber rod bundle actuator in a pressurized water nuclear reactor

International Nuclear Information System (INIS)

Martin, J.; Peletan, R.

1984-01-01

The invention concerns an absorber rod bundle actuator in a pressurized water reactor with spectral shift control. The device comprises two coaxial control bars. The inner bar is integral with the absorber rod bundle; it has an enlarged zone which acts as a proton under pressure difference across an annular seal which can be radially expanded, the pressure difference allowing to the absorber rod bundles actuating on the piston. When a pressure difference is applied, the seal expands radially by a sufficient amount to make sealing contact with the zone of larger diameter in the outer bar. The invention applies more particularly to reactors with spectral shift control using bundles of fertile rods [fr

Two Types of Genetic Interaction Implicate the Whirligig Gene of Drosophila Melanogaster in Microtubule Organization in the Flagellar Axoneme

Science.gov (United States)

Green, L. L.; Wolf, N.; McDonald, K. L.; Fuller, M. T.

1990-01-01

The mutant nc4 allele of whirligig (3-54.4) of Drosophila melanogaster fails to complement mutations in an α-tubulin locus, α1t, mutations in a β-tubulin locus, B2t, or a mutation in the haywire locus. However, wrl fails to map to any of the known α- or β-tubulin genes. The extragenic failure to complement could indicate that the wrl product participates in structural interactions with microtubule proteins. The whirligig locus appears to be haploinsufficient for male fertility. Both a deficiency of wrl and possible loss of function alleles obtained by reverting the failure to complement between wrl(nc4) and B2t(n) are dominant male sterile in a genetic background wild type for tubulin. The dominant male sterility of the revertant alleles is suppressed if the flies are also heterozygous for B2t(n), for a deficiency of α1t, or for the hay(nc2) allele. These results suggest that it is not the absolute level of wrl gene product but its level relative to tubulin or microtubule function that is important for normal spermatogenesis. The phenotype of homozygous wrl mutants suggests that the whirligig product plays a role in postmeiotic spermatid differentiation, possibly in organizing the microtubules of the sperm flagellar axoneme. Flies homozygous for either wrl(nc4) or revertant alleles are viable and female fertile but male sterile. Premeiotic and meiotic stages of spermatogenesis appear normal. However, in post-meiotic stages, flagellar axonemes show loss of the accessory microtubule on the B-subfiber of outer doublet microtubules, outer triplet instead of outer doublet microtubules, and missing central pair microtubules. PMID:2127579

Demonstrating the compatibility of Canflex fuel bundles with a CANDU 6 fuelling machine

Energy Technology Data Exchange (ETDEWEB)

Alavi, P; Oldaker, I E [Atomic Energy of Canada Ltd., Mississauga, ON (Canada); Suk, H C; Choi, C B [Korea Atomic Energy Research Inst., Taejon (Korea, Republic of)

1997-12-31

CANFLEX is a new 43-element fuel bundle, designed for high operating margins. It has many small-diameter elements in its two outer rings, and large-diameter elements in its centre rings. By this means, the linear heat ratings are lower than those of standard 37-element bundles for similar power outputs. A necessary part of the out-reactor qualification program for the CANFLEX fuel bundle design, is a demonstration of the bundle`s compatibility with the mechanical components in a CANDU 6 Fuelling Machine (FM) under typical conditions of pressure, flow and temperature. The diameter of the CANFLEX bundle is the same as that of a 37-element bundle, but the smaller-diameter elements in the outer ring result in a slightly larger end-plate diameter. Therefore, to minimize any risk of unanticipated damage to the CANDU 6 FM sidestops, a series of measurements and static laboratory tests were undertaken prior to the fuelling machine tests. The tests and measurements showed that; a) the CANFLEX bundle end plate is compatible with the FM sidestops, b) all the dimensions of the CANFLEX fuel bundle are within the specified limits. (author). 3 tabs., 3 figs.

Infinite Grassmannian and moduli space of G-bundles

International Nuclear Information System (INIS)

Kumar, S.; Ramanathan, A.

1993-03-01

Let C be a smooth irreducible projective curve and G a simply connected simple affine algebraic group of C. We study in this paper the relationship between the space of vacua defined in Conformal Field Theory and the space of sections of a line bundle on the moduli space of G-bundles over C. (author). 33 refs

An overview on rod-bundle thermal-hydraulic analyses

International Nuclear Information System (INIS)

Sha, W.T.

1980-01-01

Three methods used in rod-bundle thermal-hydraulic analysis are summarized. These methods are: (1) subchannel analysis, (2) porous medium formulation with volume porosity, surface permeability, distributed resistance and distributed heat source (sink) and, (3) bench-mark rod-bundle thermal-hydraulic analysis using a boundary-fitted coordinate system. Basic limitations and merits of each method are delineated. (orig.)

Optomechanical proposal for monitoring microtubule mechanical vibrations

Czech Academy of Sciences Publication Activity Database

Barzanjeh, Sh.; Salari, V.; Tuszynski, J. A.; Cifra, Michal; Simon, C.

2017-01-01

Roč. 96, č. 1 (2017), č. článku 012404. ISSN 2470-0045 R&D Projects: GA ČR(CZ) GA15-17102S Grant - others:AV ČR(CZ) SAV-15-22 Program:Bilaterální spolupráce Institutional support: RVO:67985882 Keywords : Vibrational modes * Microtubule * Resonance frequencies Subject RIV: BH - Optics, Masers, Lasers OBOR OECD: Optics (including laser optics and quantum optics) Impact factor: 2.366, year: 2016

Numerical investigation of supercritical water-cooled nuclear reactor in horizontal rod bundles

Energy Technology Data Exchange (ETDEWEB)

Shang Zhi, E-mail: shangzhi@tsinghua.org.c [Faculty of Engineering, Kingston University, London SW15 3DW (United Kingdom); Science and Technology Facilities Council, Daresbury Laboratory, Warrington WA4 4AD (United Kingdom); Lo, Simon, E-mail: simon.lo@uk.cd-adapco.co [CD-adapco, Trident House, Basil Hill Road, Didcot OX11 7HJ (United Kingdom)

2010-04-15

The commercial CFD code STAR-CD v4.02 is used as a numerical simulation tool for flows in the supercritical water-cooled nuclear reactor (SCWR). The basic heat transfer element in the reactor core can be considered as round rods and rod bundles. Reactors with vertical or horizontal flow in the core can be found. In vertically oriented core, symmetric characters of flow and heat transfer can be found and two-dimensional analyses are often performed. However, in horizontally oriented core the flow and heat transfer are fully three-dimensional due to the buoyancy effect. In this paper, horizontal rods and rod bundles at SCWR conditions are studied. Special STAR-CD subroutines were developed by the authors to correctly represent the dramatic change in physical properties of the supercritical water with temperature. In the rod bundle simulations, it is found that the geometry and orientation of the rod bundle have strong effects on the wall temperature distributions and heat transfers. In one orientation the square bundle has a higher wall temperature difference than other bundles. However, when the bundles are rotated by 90 deg. the highest wall temperature difference is found in the hexagon bundle. Similar analysis could be useful in design and safety studies to obtain optimum fuel rod arrangement in a SCWR.

SAS-6 engineering reveals interdependence between cartwheel and microtubules in determining centriole architecture.

Science.gov (United States)

Hilbert, Manuel; Noga, Akira; Frey, Daniel; Hamel, Virginie; Guichard, Paul; Kraatz, Sebastian H W; Pfreundschuh, Moritz; Hosner, Sarah; Flückiger, Isabelle; Jaussi, Rolf; Wieser, Mara M; Thieltges, Katherine M; Deupi, Xavier; Müller, Daniel J; Kammerer, Richard A; Gönczy, Pierre; Hirono, Masafumi; Steinmetz, Michel O

2016-04-01

Centrioles are critical for the formation of centrosomes, cilia and flagella in eukaryotes. They are thought to assemble around a nine-fold symmetric cartwheel structure established by SAS-6 proteins. Here, we have engineered Chlamydomonas reinhardtii SAS-6-based oligomers with symmetries ranging from five- to ten-fold. Expression of a SAS-6 mutant that forms six-fold symmetric cartwheel structures in vitro resulted in cartwheels and centrioles with eight- or nine-fold symmetries in vivo. In combination with Bld10 mutants that weaken cartwheel-microtubule interactions, this SAS-6 mutant produced six- to eight-fold symmetric cartwheels. Concurrently, the microtubule wall maintained eight- and nine-fold symmetries. Expressing SAS-6 with analogous mutations in human cells resulted in nine-fold symmetric centrioles that exhibited impaired length and organization. Together, our data suggest that the self-assembly properties of SAS-6 instruct cartwheel symmetry, and lead us to propose a model in which the cartwheel and the microtubule wall assemble in an interdependent manner to establish the native architecture of centrioles.

Investigations with diagnostic fuel rod bundles on Rheinsberg NPP

International Nuclear Information System (INIS)

Krauze, F.; Rudolf, G.; Shajfler, V.; Tsimke, K.

1982-01-01

In 70MW pressurized water reactor of Rheinsberg NPP diagnostic fuel rod bundles have been installed: first of DK 1 type and then of DK 2 advanced type. Three rounds of measurement were run with DK 1 bundle and one with DK 2. The diagnostic bundles are equiped with various sensors for temperature, pressure, neutron flux and mechanical stress measurements as well as with special flow rate control system which allows to reach coolant boiling within the bundle. Qualitative and quantitative description of the sensors performance during reactor operation is given. The presented experimental results are connected with: 1) working capability of the measuring devices and their calibration; 2) throttling and boiling in two regimes: a) stationary and non-stationary flow rate throbgh DK during stationary reactor operation; b) various constant levels of flow rate through DK during non-stationary reactor operation regime [ru

Involvement of microtubules in lipoprotein degradation and utilization for steroidogenesis in cultured rat luteal cells

International Nuclear Information System (INIS)

Rajan, V.P.; Menon, K.M.

1985-01-01

Cells isolated from superovulated rat ovaries metabolize low density lipoprotein (LDL) and high density lipoprotein (HDL) of human or rat origin and use the lipoprotein-derived cholesterol as a precursor for progesterone production. Under in vitro conditions, both lipoproteins are internalized and degraded in the lysosomes, although degradation of HDL is of lower magnitude than that of LDL. In this report we have examined the role of cellular microtubules in the internalization and degradation of human LDL and HDL in cultured rat luteal cells. The microtubule depolymerizing agents colchicine, podophyllotoxin, vinblastine, and nocodazole as well as taxol, deuterium oxide, and dimethyl sulfoxide, which are known to rapidly polymerize cellular tubulin into microtubules, were used to block the function of microtubules. When these antimicrotubule agents were included in the incubations, degradation of the apolipoproteins of [ 125 I]iodo-LDL and [ 125 I]iodo-HDL by the luteal cells was inhibited by 50-85% compared to untreated control values. Maximum inhibitory effects were observed when the cells were preincubated with the inhibitor for at least 4 h at 37 C before treatment with the labeled lipoprotein. Lipoprotein-stimulated progesterone production by luteal cells was also inhibited by 50% or more in the presence of antimicrotubule agents. However, basal and hCG-stimulated progesterone production were unaffected by these inhibitors. The binding of [ 125 I]iodo-LDL and [ 125 I]iodo-HDL to luteal cell plasma membrane receptors was not affected by the microtubule inhibitors. Although binding was unaffected and degradation was impaired in the presence of the inhibitors, there was no detectable accumulation of undegraded lipoprotein within the cells during the 24 h of study

Group Coupons: Interpersonal Bundling on the Internet

OpenAIRE

Yongmin Chen; Tianle Zhang

2012-01-01

Sellers sometimes offer goods for sale under both a regular price and a discount for group purchase if the consumer group reaches some minimum size. This selling practice, which we term interpersonal bundling, has been popularized on the Internet by companies such as Groupon. We explain why interpersonal bundling is a profitable strategy in the presence of demand uncertainty, and how it may further boost profits by stimulating product information dissemination. Other reasons for its profitabi...