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Sample records for akap5 disrupt dendritic

  1. Effects of AKAP5 Pro100Leu Genotype on Working Memory for Emotional Stimuli

    OpenAIRE

    Sylvia Richter; Xenia Gorny; Judith Machts; Gusalija Behnisch; Torsten Wüstenberg; Maike C Herbort; Münte, Thomas F.; Seidenbecher, Constanze I.; Schott, Björn H.

    2013-01-01

    Recent investigations addressing the role of the synaptic multiadaptor molecule AKAP5 in human emotion and behavior suggest that the AKAP5 Pro100Leu polymorphism (rs2230491) contributes to individual differences in affective control. Carriers of the less common Leu allele show a higher control of anger as indicated by behavioral measures and dACC brain response on emotional distracters when compared to Pro homozygotes. In the current fMRI study we used an emotional working memory task accordi...

  2. Effects of AKAP5 Pro100Leu genotype on working memory for emotional stimuli.

    Science.gov (United States)

    Richter, Sylvia; Gorny, Xenia; Machts, Judith; Behnisch, Gusalija; Wüstenberg, Torsten; Herbort, Maike C; Münte, Thomas F; Seidenbecher, Constanze I; Schott, Björn H

    2013-01-01

    Recent investigations addressing the role of the synaptic multiadaptor molecule AKAP5 in human emotion and behavior suggest that the AKAP5 Pro100Leu polymorphism (rs2230491) contributes to individual differences in affective control. Carriers of the less common Leu allele show a higher control of anger as indicated by behavioral measures and dACC brain response on emotional distracters when compared to Pro homozygotes. In the current fMRI study we used an emotional working memory task according to the n-back scheme with neutral and negative emotional faces as target stimuli. Pro homozygotes showed a performance advantage at the behavioral level and exhibited enhanced activation of the amygdala and fusiform face area during working memory for emotional faces. On the other hand, Leu carriers exhibited increased activation of the dACC during performance of the 2-back condition. Our results suggest that AKAP5 Pro100Leu effects on emotion processing might be task-dependent with Pro homozygotes showing lower control of emotional interference, but more efficient processing of task-relevant emotional stimuli. PMID:23383244

  3. Effects of AKAP5 Pro100Leu genotype on working memory for emotional stimuli.

    Directory of Open Access Journals (Sweden)

    Sylvia Richter

    Full Text Available Recent investigations addressing the role of the synaptic multiadaptor molecule AKAP5 in human emotion and behavior suggest that the AKAP5 Pro100Leu polymorphism (rs2230491 contributes to individual differences in affective control. Carriers of the less common Leu allele show a higher control of anger as indicated by behavioral measures and dACC brain response on emotional distracters when compared to Pro homozygotes. In the current fMRI study we used an emotional working memory task according to the n-back scheme with neutral and negative emotional faces as target stimuli. Pro homozygotes showed a performance advantage at the behavioral level and exhibited enhanced activation of the amygdala and fusiform face area during working memory for emotional faces. On the other hand, Leu carriers exhibited increased activation of the dACC during performance of the 2-back condition. Our results suggest that AKAP5 Pro100Leu effects on emotion processing might be task-dependent with Pro homozygotes showing lower control of emotional interference, but more efficient processing of task-relevant emotional stimuli.

  4. Dendrite Array Disruption by Bubbles during Re-melting in a Microgravity Environment

    Science.gov (United States)

    Grugel, Richard N.

    2012-01-01

    As part of the Pore Formation and Mobility Investigation (PFMI), Succinonitrile Water alloys consisting of aligned dendritic arrays were re-melted prior to conducting directional solidification experiments in the microgravity environment aboard the International Space Station. Thermocapillary convection initiated by bubbles at the solid-liquid interface during controlled melt back of the alloy was observed to disrupt the initial dendritic alignment. Disruption ranged from detaching large arrays to the transport of small dendrite fragments at the interface. The role of bubble size and origin is discussed along with subsequent consequences upon reinitiating controlled solidification.

  5. Disruption of an Aligned Dendritic Network by Bubbles During Re-Melting in a Microgravity Environment

    Science.gov (United States)

    Grugel, Richard N.; Brush, Lucien N.; Anilkumar, Amrutur V.

    2012-01-01

    The quiescent Microgravity environment can be quite dynamic. Thermocapillary flow about "large" static bubbles on the order of 1mm in diameter was easily observed by following smaller tracer bubbles. The bubble induced flow was seen to disrupt a large dendritic array, effectively distributing free branches about the solid-liquid interface. "Small" dynamic bubbles were observed to travel at fast velocities through the mushy zone with the implication of bringing/detaching/redistributing dendrite arm fragments at the solid-liquid interface. Large and small bubbles effectively re-orient/re-distribute dendrite branches/arms/fragments at the solid liquid interface. Subsequent initiation of controlled directional solidification results in growth of dendrites having random orientations which significantly compromises the desired science.

  6. ER Stress Sensor XBP1 Controls Anti-tumor Immunity by Disrupting Dendritic Cell Homeostasis.

    Science.gov (United States)

    Cubillos-Ruiz, Juan R; Silberman, Pedro C; Rutkowski, Melanie R; Chopra, Sahil; Perales-Puchalt, Alfredo; Song, Minkyung; Zhang, Sheng; Bettigole, Sarah E; Gupta, Divya; Holcomb, Kevin; Ellenson, Lora H; Caputo, Thomas; Lee, Ann-Hwee; Conejo-Garcia, Jose R; Glimcher, Laurie H

    2015-06-18

    Dendritic cells (DCs) are required to initiate and sustain T cell-dependent anti-cancer immunity. However, tumors often evade immune control by crippling normal DC function. The endoplasmic reticulum (ER) stress response factor XBP1 promotes intrinsic tumor growth directly, but whether it also regulates the host anti-tumor immune response is not known. Here we show that constitutive activation of XBP1 in tumor-associated DCs (tDCs) drives ovarian cancer (OvCa) progression by blunting anti-tumor immunity. XBP1 activation, fueled by lipid peroxidation byproducts, induced a triglyceride biosynthetic program in tDCs leading to abnormal lipid accumulation and subsequent inhibition of tDC capacity to support anti-tumor T cells. Accordingly, DC-specific XBP1 deletion or selective nanoparticle-mediated XBP1 silencing in tDCs restored their immunostimulatory activity in situ and extended survival by evoking protective type 1 anti-tumor responses. Targeting the ER stress response should concomitantly inhibit tumor growth and enhance anti-cancer immunity, thus offering a unique approach to cancer immunotherapy.

  7. ER Stress Sensor XBP1 Controls Anti-tumor Immunity by Disrupting Dendritic Cell Homeostasis

    Science.gov (United States)

    Cubillos-Ruiz, Juan R.; Silberman, Pedro C.; Rutkowski, Melanie R.; Chopra, Sahil; Perales-Puchalt, Alfredo; Song, Minkyung; Zhang, Sheng; Bettigole, Sarah E.; Gupta, Divya; Holcomb, Kevin; Ellenson, Lora H.; Caputo, Thomas; Lee, Ann-Hwee; Conejo-Garcia, Jose R.; Glimcher, Laurie H.

    2015-01-01

    SUMMARY Dendritic cells (DCs) are required to initiate and sustain T cell-dependent anti-cancer immunity. However, tumors often evade immune control by crippling normal DC function. The endoplasmic reticulum (ER) stress response factor XBP1 promotes intrinsic tumor growth directly, but whether it also regulates the host anti-tumor immune response is not known. Here we show that constitutive activation of XBP1 in tumor-associated DCs (tDCs) drives ovarian cancer (OvCa) progression by blunting anti-tumor immunity. XBP1 activation, fueled by lipid peroxidation byproducts, induced a triglyceride biosynthetic program in tDCs leading to abnormal lipid accumulation and subsequent inhibition of tDC capacity to support anti-tumor T cells. Accordingly, DC-specific XBP1 deletion or selective nanoparticle-mediated XBP1 silencing in tDCs restored their immunostimulatory activity in situ and extended survival by evoking protective type 1 anti-tumor responses. Targeting the ER stress response should concomitantly inhibit tumor growth and enhance anti-cancer immunity, thus offering a unique approach to cancer immunotherapy. PMID:26073941

  8. Disruption of Early Tumor Necrosis Factor Alpha Signaling Prevents Classical Activation of Dendritic Cells in Lung-Associated Lymph Nodes and Development of Protective Immunity against Cryptococcal Infection

    Directory of Open Access Journals (Sweden)

    Jintao Xu

    2016-07-01

    Full Text Available Anti-tumor necrosis factor alpha (anti-TNF-α therapies have been increasingly used to treat inflammatory diseases and are associated with increased risk of invasive fungal infections, including Cryptococcus neoformans infection. Using a mouse model of cryptococcal infection, we investigated the mechanism by which disruption of early TNF-α signaling results in the development of nonprotective immunity against C. neoformans. We found that transient depletion of TNF-α inhibited pulmonary fungal clearance and enhanced extrapulmonary dissemination of C. neoformans during the adaptive phase of the immune response. Higher fungal burdens in TNF-α-depleted mice were accompanied by markedly impaired Th1 and Th17 responses in the infected lungs. Furthermore, early TNF-α depletion also resulted in disrupted transcriptional initiation of the Th17 polarization program and subsequent upregulation of Th1 genes in CD4+ T cells in the lung-associated lymph nodes (LALN of C. neoformans-infected mice. These defects in LALN T cell responses were preceded by a dramatic shift from a classical toward an alternative activation of dendritic cells (DC in the LALN of TNF-α-depleted mice. Taken together, our results indicate that early TNF-α signaling is required for optimal DC activation, and the initial Th17 response followed by Th1 transcriptional prepolarization of T cells in the LALN, which further drives the development of protective immunity against cryptococcal infection in the lungs. Thus, administration of anti-TNF-α may introduce a particularly greater risk for newly acquired fungal infections that require generation of protective Th1/Th17 responses for their containment and clearance.

  9. Disruption of Early Tumor Necrosis Factor Alpha Signaling Prevents Classical Activation of Dendritic Cells in Lung-Associated Lymph Nodes and Development of Protective Immunity against Cryptococcal Infection

    Science.gov (United States)

    Xu, Jintao; Eastman, Alison J.; Flaczyk, Adam; Neal, Lori M.; Zhao, Guolei; Carolan, Jacob; Malachowski, Antoni N.; Stolberg, Valerie R.; Yosri, Mohammed; Chensue, Stephen W.; Curtis, Jeffrey L.; Osterholzer, John J.

    2016-01-01

    ABSTRACT Anti-tumor necrosis factor alpha (anti-TNF-α) therapies have been increasingly used to treat inflammatory diseases and are associated with increased risk of invasive fungal infections, including Cryptococcus neoformans infection. Using a mouse model of cryptococcal infection, we investigated the mechanism by which disruption of early TNF-α signaling results in the development of nonprotective immunity against C. neoformans. We found that transient depletion of TNF-α inhibited pulmonary fungal clearance and enhanced extrapulmonary dissemination of C. neoformans during the adaptive phase of the immune response. Higher fungal burdens in TNF-α-depleted mice were accompanied by markedly impaired Th1 and Th17 responses in the infected lungs. Furthermore, early TNF-α depletion also resulted in disrupted transcriptional initiation of the Th17 polarization program and subsequent upregulation of Th1 genes in CD4+ T cells in the lung-associated lymph nodes (LALN) of C. neoformans-infected mice. These defects in LALN T cell responses were preceded by a dramatic shift from a classical toward an alternative activation of dendritic cells (DC) in the LALN of TNF-α-depleted mice. Taken together, our results indicate that early TNF-α signaling is required for optimal DC activation, and the initial Th17 response followed by Th1 transcriptional prepolarization of T cells in the LALN, which further drives the development of protective immunity against cryptococcal infection in the lungs. Thus, administration of anti-TNF-α may introduce a particularly greater risk for newly acquired fungal infections that require generation of protective Th1/Th17 responses for their containment and clearance. PMID:27406560

  10. Developmental disorders of the brain can be caused by PCBs; low doses of hydroxy-PCBs disrupt thyroid hormone-dependent dendrite formation from Purkinje neurons in culture

    Energy Technology Data Exchange (ETDEWEB)

    Kuroda, Y.; Kimura-Kuroda, J. [Tokyo Metropol. Inst. for Neuroscience, Tokyo (Japan); Nagata, I. [CREST/ JST, Tokyo (Japan)

    2004-09-15

    Exposure to some environmental chemicals during the perinatal period causes developmental disorders of the brain. Cognitive impairment and hyperactivity in infants were reported in Taiwan, known as Yu-cheng incidents caused by the accidental contamination of polychlorinated biphenyls (PCBs). Together with recent experimental data, Kuroda proposes a hypothesis that spatio-temporal disruptions of developing neuronal circuits by PCB exposure can cause the comobidity of learning disorders (LD), attention deficit hyperactivity disorder (ADHD) and autsm with the co-exposure to other environmental chemicals. PCBs and hydroxylated PCBs (OH-PCBs) have similar chemical structures to thyroid hormones (TH), thyroxine (T4) and triiodothyronine (T3). TH deficiency in the perinatal period causes cretinism children with severe cognitive and mental retardation. In primate model, Rice demonstrates that postnatal exposure to PCBs can dramatically influence later behavioral function. Epidemiological studies also indicate the possible developmental neurotoxicity of PCBs accumulated in human bodies. However, the precise underlying mechanisms and which types of PCB or OH-PCB with such effects have yet to be elucidated. It is important to establish a simple, reproducible, and sensitive in vitro assay for determining the effects of PCBs and OH-PCBs on the development of the central nervous system. Recently Iwasaki et al. established a reporter assay system and disclosed that low doses of PCBs potentially interfere TH-dependent gene expressions. This is the first demonstration that PCBs and OH-PCBs directly affect TH-receptor (TR)-mediated gene expressions crucial to the brain development, through unique mechanism. We also have demonstrated TH-dependent development of Purkinje neurons in vitro using a serum-free chemically defined medium. The degree of dendritic development of Purkinje cells is TH dose-dependent and exhibits high sensitivity in the pM order. Therefore, in the present study

  11. Thrombin cleavage of osteopontin disrupts a pro-chemotactic sequence for dendritic cells, which is compensated by the release of its pro-chemotactic C-terminal fragment.

    Science.gov (United States)

    Shao, Zhifei; Morser, John; Leung, Lawrence L K

    2014-09-26

    Thrombin cleavage alters the function of osteopontin (OPN) by exposing an integrin binding site and releasing a chemotactic C-terminal fragment. Here, we examined thrombin cleavage of OPN in the context of dendritic cell (DC) migration to define its functional domains. Full-length OPN (OPN-FL), thrombin-cleaved N-terminal fragment (OPN-R), thrombin- and carboxypeptidase B2-double-cleaved N-terminal fragment (OPN-L), and C-terminal fragment (OPN-CTF) did not have intrinsic chemotactic activity, but all potentiated CCL21-induced DC migration. OPN-FL possessed the highest potency, whereas OPNRAA-FL had substantially less activity, indicating the importance of RGD. We identified a conserved (168)RSKSKKFRR(176) sequence on OPN-FL that spans the thrombin cleavage site, and it demonstrated potent pro-chemotactic effects on CCL21-induced DC migration. OPN-FLR168A had reduced activity, and the double mutant OPNRAA-FLR168A had even lower activity, indicating that these functional domains accounted for most of the pro-chemotactic activity of OPN-FL. OPN-CTF also possessed substantial pro-chemotactic activity, which was fully expressed upon thrombin cleavage and its release from the intact protein, because OPN-CTF was substantially more active than OPNRAA-FLR168A containing the OPN-CTF sequence within the intact protein. OPN-R and OPN-L possessed similar potency, indicating that the newly exposed C-terminal SVVYGLR sequence in OPN-R was not involved in the pro-chemotactic effect. OPN-FL and OPN-CTF did not directly bind to the CD44 standard form or CD44v6. In conclusion, thrombin cleavage of OPN disrupts a pro-chemotactic sequence in intact OPN, and its loss of pro-chemotactic activity is compensated by the release of OPN-CTF, which assumes a new conformation and possesses substantial activity in enhancing chemokine-induced migration of DCs. PMID:25112870

  12. Development of dendrite polarity in Drosophila neurons

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    Hill Sarah E

    2012-10-01

    Full Text Available Abstract Background Drosophila neurons have dendrites that contain minus-end-out microtubules. This microtubule arrangement is different from that of cultured mammalian neurons, which have mixed polarity microtubules in dendrites. Results To determine whether Drosophila and mammalian dendrites have a common microtubule organization during development, we analyzed microtubule polarity in Drosophila dendritic arborization neuron dendrites at different stages of outgrowth from the cell body in vivo. As dendrites initially extended, they contained mixed polarity microtubules, like mammalian neurons developing in culture. Over a period of several days this mixed microtubule array gradually matured to a minus-end-out array. To determine whether features characteristic of dendrites were localized before uniform polarity was attained, we analyzed dendritic markers as dendrites developed. In all cases the markers took on their characteristic distribution while dendrites had mixed polarity. An axonal marker was also quite well excluded from dendrites throughout development, although this was perhaps more efficient in mature neurons. To confirm that dendrite character could be acquired in Drosophila while microtubules were mixed, we genetically disrupted uniform dendritic microtubule organization. Dendritic markers also localized correctly in this case. Conclusions We conclude that developing Drosophila dendrites initially have mixed microtubule polarity. Over time they mature to uniform microtubule polarity. Dendrite identity is established before the mature microtubule arrangement is attained, during the period of mixed microtubule polarity.

  13. The HPV16 E7 Oncoprotein Disrupts Dendritic Cell Function and Induces the Systemic Expansion of CD11b+Gr1+ Cells in a Transgenic Mouse Model

    Science.gov (United States)

    Damian-Morales, Gabriela; Serafín-Higuera, Nicolás; Moreno-Eutimio, Mario Adán; Cortés-Malagón, Enoc M.; Bonilla-Delgado, José; Rodríguez-Uribe, Genaro; Ocadiz-Delgado, Rodolfo; Lambert, Paul F.

    2016-01-01

    Objective. The aim of this study was to analyze the effects of the HPV16 E7 oncoprotein on dendritic cells (DCs) and CD11b+Gr1+ cells using the K14E7 transgenic mouse model. Materials and Methods. The morphology of DCs was analyzed in male mouse skin on epidermal sheets using immunofluorescence and confocal microscopy. Flow cytometry was used to determine the percentages of DCs and CD11b+Gr1+ cells in different tissues and to evaluate the migration of DCs. Results. In the K14E7 mouse model, the morphology of Langerhans cells and the migratory activity of dendritic cells were abnormal. An increase in CD11b+Gr1+ cells was observed in the blood and skin of K14E7 mice, and molecules related to CD11b+Gr1+ chemoattraction (MCP1 and S100A9) were upregulated. Conclusions. These data suggest that the HPV16 E7 oncoprotein impairs the function and morphology of DCs and induces the systemic accumulation of CD11b+Gr1+ cells. PMID:27478837

  14. Dendritic cells are stressed out in tumor.

    Science.gov (United States)

    Maj, Tomasz; Zou, Weiping

    2015-09-01

    A recently paper published in Cell reports that dendritic cells (DCs) are dysfunctional in the tumor environment. Tumor impairs DC function through induction of endoplasmic reticulum stress response and subsequent disruption of lipid metabolic homeostasis.

  15. Spiraling eutectic dendrites

    OpenAIRE

    Pusztai, Tamás; Rátkai, László; Szállás, Attila; Gránásy, László

    2013-01-01

    Eutectic dendrites forming in a model ternary system have been studied using the phase-field theory. The eutectic and one-phase dendrites have similar forms, and the tip radius scales with the interface free energy as for one-phase dendrites. The steady-state eutectic patterns appearing on these two-phase dendrites include concentric rings, and single- to multiarm spirals, of which the fluctuations choose, a stochastic phenomenon characterized by a peaked probability distribution. The number ...

  16. Free dendritic growth

    Science.gov (United States)

    Glicksman, M. E.

    1984-01-01

    Free dendritic growth refers to the unconstrained development of crystals within a supercooled melt, which is the classical 'dendrite problem'. Great strides have been taken in recent years in both the theoretical understanding of dendritic growth and its experimental status. The development of this field will be sketched, showing that transport theory and interfacial thermodynamics (capillarity theory) were sufficient ingredients to develop a truly predictive model of dendrite formation. The convenient, but incorrect, notion of 'maximum velocity' was used for many years to estimate the behavior of dendritic transformations until supplanted by modern dynamic stability theory. The proper combinations of transport theory and morphological stability seem to able to predict the salient aspects of dendritic growth, especially in the neighborhood of the tip. The overall development of cast microstructures, such as equiaxed zone formation, rapidly solidified microstructures, etc., also seems to contain additional non-deterministic features which lie outside the current theories discussed here.

  17. Family Disruptions

    Science.gov (United States)

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Life Listen Español Text Size Email Print Share Family Disruptions Page Content Article Body No matter how ...

  18. Sustainable Disruptions

    DEFF Research Database (Denmark)

    Friis, Silje Alberthe Kamille; Kjær, Lykke Bloch

    2016-01-01

    Since 2012 the Sustainable Disruptions (SD) project at the Laboratory for Sustainability at Design School Kolding (DK) has developed and tested a set of design thinking tools, specifically targeting the barriers to economically, socially, and environmentally sustainable business development...

  19. Disrupted Disclosure

    DEFF Research Database (Denmark)

    Krause Hansen, Hans; Uldam, Julie

    appearances become challenged through disruptive disclosures in mediaenvironments characterized by multiple levels of visibility, with companies both observing andbeing observed by civil society groups that criticize them; (c) why and how the mobilization aroundtransparency and ensuing practices...

  20. NMDA spike/plateau potentials in dendrites of thalamocortical neurons.

    Science.gov (United States)

    Augustinaite, Sigita; Kuhn, Bernd; Helm, Paul Johannes; Heggelund, Paul

    2014-08-13

    Dendritic NMDA spike/plateau potentials, first discovered in cortical pyramidal neurons, provide supralinear integration of synaptic inputs on thin and distal dendrites, thereby increasing the impact of these inputs on the soma. The more specific functional role of these potentials has been difficult to clarify, partly due to the complex circuitry of cortical neurons. Thalamocortical (TC) neurons in the dorsal lateral geniculate nucleus participate in simpler circuits. They receive their primary afferent input from retina and send their output to visual cortex. Cortex, in turn, regulates this output through massive feedback to distal dendrites of the TC neurons. The TC neurons can operate in two modes related to behavioral states: burst mode prevailing during sleep, when T-type calcium bursts largely disrupt the transfer of signals from retina to cortex, and tonic mode, which provides reliable transfer of retinal signals to cortex during wakefulness. We studied dendritic potentials in TC neurons with combined two-photon calcium imaging and whole-cell recording of responses to local dendritic glutamate iontophoresis in acute brain slices from mice. We found that NMDA spike/plateaus can be elicited locally at distal dendrites of TC neurons. We suggest that these dendritic potentials have important functions in the cortical regulation of thalamocortical transmission. NMDA spike/plateaus can induce shifts in the functional mode from burst to tonic by blockade of T-type calcium conductances. Moreover, in tonic mode, they can facilitate the transfer of retinal signals to cortex by depolarization of TC neurons. PMID:25122891

  1. Random fractal dendrites

    OpenAIRE

    Croydon, David (David Alexander); Hambly, Ben M.; Dr. Ben Hambly

    2006-01-01

    Dendrites are tree-like topological spaces, and in this thesis, the physical characteristics of various random fractal versions of this type of set are investigated. This work will contribute to the development of analysis on fractals, an area which has grown considerably over the last twenty years. First, a collection of random self-similar dendrites is constructed, and their Hausdorff dimension is calculated. Previous results determining this quantity for random self-simi...

  2. Optimization principles of dendritic structure

    Directory of Open Access Journals (Sweden)

    Borst Alexander

    2007-06-01

    Full Text Available Abstract Background Dendrites are the most conspicuous feature of neurons. However, the principles determining their structure are poorly understood. By employing cable theory and, for the first time, graph theory, we describe dendritic anatomy solely on the basis of optimizing synaptic efficacy with minimal resources. Results We show that dendritic branching topology can be well described by minimizing the path length from the neuron's dendritic root to each of its synaptic inputs while constraining the total length of wiring. Tapering of diameter toward the dendrite tip – a feature of many neurons – optimizes charge transfer from all dendritic synapses to the dendritic root while housekeeping the amount of dendrite volume. As an example, we show how dendrites of fly neurons can be closely reconstructed based on these two principles alone.

  3. Disrupting Business

    DEFF Research Database (Denmark)

    Cox, Geoff; Bazzichelli, Tatiana

    Disruptive Business explores some of the interconnections between art, activism and the business concept of disruptive innovation. With a backdrop of the crisis of financial capitalism, austerity cuts in the cultural sphere, the idea is to focus on potential art strategies in relation to a broken...... economy. In a perverse way, we ask whether this presents new opportunities for cultural producers to achieve more autonomy over their production process. If it is indeed possible, or desirable, what alternative business models emerge? The book is concerned broadly with business as material for reinvention...

  4. Tropomodulin isoforms utilize specific binding functions to modulate dendrite development.

    Science.gov (United States)

    Gray, Kevin T; Suchowerska, Alexandra K; Bland, Tyler; Colpan, Mert; Wayman, Gary; Fath, Thomas; Kostyukova, Alla S

    2016-06-01

    Tropomodulins (Tmods) cap F-actin pointed ends and have altered expression in the brain in neurological diseases. The function of Tmods in neurons has been poorly studied and their role in neurological diseases is entirely unknown. In this article, we show that Tmod1 and Tmod2, but not Tmod3, are positive regulators of dendritic complexity and dendritic spine morphology. Tmod1 increases dendritic branching distal from the cell body and the number of filopodia/thin spines. Tmod2 increases dendritic branching proximal to the cell body and the number of mature dendritic spines. Tmods utilize two actin-binding sites and two tropomyosin (Tpm)-binding sites to cap F-actin. Overexpression of Tmods with disrupted Tpm-binding sites indicates that Tmod1 and Tmod2 differentially utilize their Tpm- and actin-binding sites to affect morphology. Disruption of Tmod1's Tpm-binding sites abolished the overexpression phenotype. In contrast, overexpression of the mutated Tmod2 caused the same phenotype as wild type overexpression. Proximity ligation assays indicate that the mutated Tmods are shuttled similarly to wild type Tmods. Our data begins to uncover the roles of Tmods in neural development and the mechanism by which Tmods alter neural morphology. These observations in combination with altered Tmod expression found in several neurological diseases also suggest that dysregulation of Tmod expression may be involved in the pathology of these diseases. © 2016 Wiley Periodicals, Inc. PMID:27126680

  5. Transport Processes in Dendritic Crystallization

    Science.gov (United States)

    Glicksman, M. E.

    1984-01-01

    Free dentritic growth refers to the unconstrained development of crystals within a supercooled melt, which is the classical dendrite problem. The development of theoretical understanding of dendritic growth and its experimental status is sketched showing that transport theory and interfacial thermodynamics (capillarity theory) are insufficient ingredients to develop a truly predictive model of dendrite formation. The convenient, but incorrect, notion of maximum velocity was used for many years to estimate the behavior of dendritic transformations until supplanted by modern dynamic stability theory. The proper combinations of transport theory and morphological stability seem to be able to predict the salient aspects of dendritic growth, especially in the neighborhood of the tip.

  6. Modification of dendritic development.

    Science.gov (United States)

    Feria-Velasco, Alfredo; del Angel, Alma Rosa; Gonzalez-Burgos, Ignacio

    2002-01-01

    Since 1890 Ramón y Cajal strongly defended the theory that dendrites and their processes and spines had a function of not just nutrient transport to the cell body, but they had an important conductive role in neural impulse transmission. He extensively discussed and supported this theory in the Volume 1 of his extraordinary book Textura del Sistema Nervioso del Hombre y de los Vertebrados. Also, Don Santiago significantly contributed to a detailed description of the various neural components of the hippocampus and cerebral cortex during development. Extensive investigation has been done in the last Century related to the functional role of these complex brain regions, and their association with learning, memory and some limbic functions. Likewise, the organization and expression of neuropsychological qualities such as memory, exploratory behavior and spatial orientation, among others, depend on the integrity and adequate functional activity of the cerebral cortex and hippocampus. It is known that brain serotonin synthesis and release depend directly and proportionally on the availability of its precursor, tryptophan (TRY). By using a chronic TRY restriction model in rats, we studied their place learning ability in correlation with the dendritic spine density of pyramidal neurons in field CA1 of the hippocampus during postnatal development. We have also reported alterations in the maturation pattern of the ability for spontaneous alternation and task performance evaluating short-term memory, as well as adverse effects on the density of dendritic spines of hippocampal CA1 field pyramidal neurons and on the dendritic arborization and the number of dendritic spines of pyramidal neurons from the third layer of the prefrontal cortex using the same model of TRY restriction. The findings obtained in these studies employing a modified Golgi method, can be interpreted as a trans-synaptic plastic response due to understimulation of serotoninergic receptors located in the

  7. Modification of dendritic development.

    Science.gov (United States)

    Feria-Velasco, Alfredo; del Angel, Alma Rosa; Gonzalez-Burgos, Ignacio

    2002-01-01

    Since 1890 Ramón y Cajal strongly defended the theory that dendrites and their processes and spines had a function of not just nutrient transport to the cell body, but they had an important conductive role in neural impulse transmission. He extensively discussed and supported this theory in the Volume 1 of his extraordinary book Textura del Sistema Nervioso del Hombre y de los Vertebrados. Also, Don Santiago significantly contributed to a detailed description of the various neural components of the hippocampus and cerebral cortex during development. Extensive investigation has been done in the last Century related to the functional role of these complex brain regions, and their association with learning, memory and some limbic functions. Likewise, the organization and expression of neuropsychological qualities such as memory, exploratory behavior and spatial orientation, among others, depend on the integrity and adequate functional activity of the cerebral cortex and hippocampus. It is known that brain serotonin synthesis and release depend directly and proportionally on the availability of its precursor, tryptophan (TRY). By using a chronic TRY restriction model in rats, we studied their place learning ability in correlation with the dendritic spine density of pyramidal neurons in field CA1 of the hippocampus during postnatal development. We have also reported alterations in the maturation pattern of the ability for spontaneous alternation and task performance evaluating short-term memory, as well as adverse effects on the density of dendritic spines of hippocampal CA1 field pyramidal neurons and on the dendritic arborization and the number of dendritic spines of pyramidal neurons from the third layer of the prefrontal cortex using the same model of TRY restriction. The findings obtained in these studies employing a modified Golgi method, can be interpreted as a trans-synaptic plastic response due to understimulation of serotoninergic receptors located in the

  8. Homophilic Protocadherin Cell-Cell Interactions Promote Dendrite Complexity

    Directory of Open Access Journals (Sweden)

    Michael J. Molumby

    2016-05-01

    Full Text Available Growth of a properly complex dendrite arbor is a key step in neuronal differentiation and a prerequisite for neural circuit formation. Diverse cell surface molecules, such as the clustered protocadherins (Pcdhs, have long been proposed to regulate circuit formation through specific cell-cell interactions. Here, using transgenic and conditional knockout mice to manipulate γ-Pcdh repertoire in the cerebral cortex, we show that the complexity of a neuron’s dendritic arbor is determined by homophilic interactions with other cells. Neurons expressing only one of the 22 γ-Pcdhs can exhibit either exuberant or minimal dendrite complexity, depending only on whether surrounding cells express the same isoform. Furthermore, loss of astrocytic γ-Pcdhs, or disruption of astrocyte-neuron homophilic matching, reduces dendrite complexity cell non-autonomously. Our data indicate that γ-Pcdhs act locally to promote dendrite arborization via homophilic matching, and they confirm that connectivity in vivo depends on molecular interactions between neurons and between neurons and astrocytes.

  9. Dendritic Cells and Liver Fibrosis

    OpenAIRE

    Rahman, Adeeb H.; Aloman, Costica

    2013-01-01

    Dendritic cells are a relative rare population of specialized antigen presenting cells that are distributed through most lymphoid and non-lymphoid tissues and play a critical role in linking the innate and adaptive arms of the immune system. The liver contains a heterogeneous population of dendritic cells that may contribute to liver inflammation and fibrosis through a number of mechanisms. This review summarizes current knowledge on the development and characterization of liver dendritic cel...

  10. Dendrite Injury Triggers DLK-Independent Regeneration

    Directory of Open Access Journals (Sweden)

    Michelle C. Stone

    2014-01-01

    Full Text Available Axon injury triggers regeneration through activation of a conserved kinase cascade, which includes the dual leucine zipper kinase (DLK. Although dendrites are damaged during stroke, traumatic brain injury, and seizure, it is not known whether mature neurons monitor dendrite injury and initiate regeneration. We probed the response to dendrite damage using model Drosophila neurons. Two larval neuron types regrew dendrites in distinct ways after all dendrites were removed. Dendrite regeneration was also triggered by injury in adults. Next, we tested whether dendrite injury was initiated with the same machinery as axon injury. Surprisingly, DLK, JNK, and fos were dispensable for dendrite regeneration. Moreover, this MAP kinase pathway was not activated by injury to dendrites. Thus, neurons respond to dendrite damage and initiate regeneration without using the conserved DLK cascade that triggers axon regeneration.

  11. An inverse approach for elucidating dendritic function

    Directory of Open Access Journals (Sweden)

    Benjamin Torben-Nielsen

    2010-09-01

    Full Text Available We outline an inverse approach for investigating dendritic function-structure relationships by optimizing dendritic trees for a-priori chosen computational functions. The inverse approach can be applied in two different ways. First, we can use it as a `hypothesis generator' in which we optimize dendrites for a function of general interest. The optimization yields an artificial dendrite that is subsequently compared to real neurons. This comparison potentially allows us to propose hypotheses about the function of real neurons. In this way, we investigated dendrites that optimally perform input-order detection. Second, we can use it as a `function confirmation' by optimizing dendrites for functions hypothesized to be performed by classes of neurons. If the optimized, artificial, dendrites resemble the dendrites of real neurons the artificial dendrites corroborate the hypothesized function of the real neuron. Moreover, properties of the artificial dendrites can lead to predictions about yet unmeasured properties. In this way, we investigated wide-field motion integration performed by the VS cells of the fly visual system. In outlining the inverse approach and two applications, we also elaborate on the nature of dendritic function. We furthermore discuss the role of optimality in assigning functions to dendrites and point out interesting future directions.

  12. Targeting vaccines to dendritic cells

    DEFF Research Database (Denmark)

    Foged, Camilla; Sundblad, Anne; Hovgaard, Lars

    2002-01-01

    Dendritic cells (DC) are specialized antigen presenting cells (APC) with a remarkable ability to take up antigens and stimulate major histocompatibility complex (MHC)-restricted specific immune responses. Recent discoveries have shown that their role in initiating primary immune responses seems t...

  13. Monocyte-derived dendritic cells

    OpenAIRE

    Kuhn, Sabine; Ronchese, Franca

    2013-01-01

    The elicitation of efficient antitumor immune responses requires the optimal activation of tumor-associated dendritic cells (DCs). Our comparison of the effect of various immunostimulatory treatments on DCs revealed that the best predictor of the success of immunotherapy is not the activation of existing DC populations, but the appearance of a population of monocyte-derived DC in tumor-draining lymph nodes.

  14. Intrinsic and extrinsic mechanisms of dendritic morphogenesis.

    Science.gov (United States)

    Dong, Xintong; Shen, Kang; Bülow, Hannes E

    2015-01-01

    The complex, branched morphology of dendrites is a cardinal feature of neurons and has been used as a criterion for cell type identification since the beginning of neurobiology. Regulated dendritic outgrowth and branching during development form the basis of receptive fields for neurons and are essential for the wiring of the nervous system. The cellular and molecular mechanisms of dendritic morphogenesis have been an intensely studied area. In this review, we summarize the major experimental systems that have contributed to our understandings of dendritic development as well as the intrinsic and extrinsic mechanisms that instruct the neurons to form cell type-specific dendritic arbors. PMID:25386991

  15. Microtubule nucleation and organization in dendrites.

    Science.gov (United States)

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

    2016-07-01

    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

  16. Phase field modeling of dendritic coarsening during isothermal

    Directory of Open Access Journals (Sweden)

    Zhang Yutuo

    2011-08-01

    Full Text Available Dendritic coarsening in Al-2mol%Si alloy during isothermal solidification at 880K was investigated by phase field modeling. Three coarsening mechanisms operate in the alloy: (a melting of small dendrite arms; (b coalescence of dendrites near the tips leading to the entrapment of liquid droplets; (c smoothing of dendrites. Dendrite melting is found to be dominant in the stage of dendritic growth, whereas coalescence of dendrites and smoothing of dendrites are dominant during isothermal holding. The simulated results provide a better understanding of dendrite coarsening during isothermal solidification.

  17. Lipid dynamics at dendritic spines.

    Science.gov (United States)

    Dotti, Carlos Gerardo; Esteban, Jose Antonio; Ledesma, María Dolores

    2014-01-01

    Dynamic changes in the structure and composition of the membrane protrusions forming dendritic spines underlie memory and learning processes. In recent years a great effort has been made to characterize in detail the protein machinery that controls spine plasticity. However, we know much less about the involvement of lipids, despite being major membrane components and structure determinants. Moreover, protein complexes that regulate spine plasticity depend on specific interactions with membrane lipids for proper function and accurate intracellular signaling. In this review we gather information available on the lipid composition at dendritic spine membranes and on its dynamics. We pay particular attention to the influence that spine lipid dynamism has on glutamate receptors, which are key regulators of synaptic plasticity.

  18. Optimization of human dendritic cell sample preparation for mass spectrometry-based proteomics studies

    OpenAIRE

    Zhang, Ying; Bottinelli, Dario; Lisacek, Frédérique; Luban, Jeremy; De Castillia, Caterina Strambio; Varesio, Emmanuel; Hopfgartner, Gérard

    2015-01-01

    Dendritic cells (DCs) are specialized leukocytes that orchestrate the adaptive immune response. Mass spectrometry based proteomic study of these cells presents technical challenges, especially when the DCs are human in origin due to the paucity of available biological material. Here, to maximize mass spectrometry coverage of the global human DC proteome, different cell disruption methods, lysis conditions, protein precipitation, and protein pellet solubilisation and denaturation methods were ...

  19. Development of Dendritic Cell System

    Institute of Scientific and Technical Information of China (English)

    Li Wu; Aleksandar Dakic

    2004-01-01

    The dendritic cell system contains conventional dendritic cells (DCs) and plasmacytoid pre-dendritic cells (pDCs). Both DCs and pDCs are bone marrow derived cells. Although the common functions of DCs are antigen-processing and T-lymphocyte activation, they differ in surface markers, migratory patterns, and cytokine output. These differences can determine the fate of the T cells they activate. Several subsets of mature DCs have been described in both mouse and human and the developmental processes of these specialized DC subsets have been studied extensively. The original concept that all DCs were of myeloid origin was questioned by several recent studies, which demonstrated that in addition to the DCs derived from myeloid precursors,some DCs could also be efficiently generated from lymphoid-restricted precursors. Moreover, it has been shown recently that both conventional DCs and pDCs can be generated by the Flt3 expressing hemopoietic progenitors regardless of their myeloid- or lymphoid-origin. These findings suggest an early developmental flexibility of precursors for DCs and pDCs. This review summarizes some recent observations on the development of DC system in both human and mouse.

  20. Development of Dendritic Cell System

    Institute of Scientific and Technical Information of China (English)

    LiWu; AleksandarDakic

    2004-01-01

    The dendritic cell system contains conventional dendritic cells (DCs) and plasmacytoid pre-dendritic cells (pDCs). Both DCs and pDCs are bone marrow derived calls. Although the common functions of DCs are antigen-processing and T-lymphocyte activation, they differ in surface markers, migratory patterns, and cytokine output. These differences can determine the fate of the T cells they activate. Several subsets of mature DCs have been described in both mouse and human and the developmental processes of these specialized DC subsets have been studied extensively. The original concept that all DCs were of myeloid origin was questioned by several recent studies, which demonstrated that in addition to the DCs derived from myeloid precursors, some DCs could also be efficiently generated from lymphoid-restricted precursors. Moreover, it has been shown recently that both conventional DCs and pDCs can be generated by the Fit3 expressing hemopoietic progenitors regardless of their myeloid- or lymphoid-origin. These findings suggest an early developmental flexibility of precursors for DCs and pDCs. This review summarizes some recent observations on the development of DC system in both human and mouse. Cellular & Molecular Immunology. 2004;1(2):112-118.

  1. Dendritic web silicon for solar cell application

    Science.gov (United States)

    Seidensticker, R. G.

    1977-01-01

    The dendritic web process for growing long thin ribbon crystals of silicon and other semiconductors is described. Growth is initiated from a thin wirelike dendrite seed which is brought into contact with the melt surface. Initially, the seed grows laterally to form a button at the melt surface; when the seed is withdrawn, needlelike dendrites propagate from each end of the button into the melt, and the web portion of the crystal is formed by the solidification of the liquid film supported by the button and the bounding dendrites. Apparatus used for dendritic web growth, material characteristics, and the two distinctly different mechanisms involved in the growth of a single crystal are examined. The performance of solar cells fabricated from dendritic web material is indistinguishable from the performance of cells fabricated from Czochralski grown material.

  2. Transcranial magnetic stimulation (TMS) inhibits cortical dendrites.

    Science.gov (United States)

    Murphy, Sean C; Palmer, Lucy M; Nyffeler, Thomas; Müri, René M; Larkum, Matthew E

    2016-03-18

    One of the leading approaches to non-invasively treat a variety of brain disorders is transcranial magnetic stimulation (TMS). However, despite its clinical prevalence, very little is known about the action of TMS at the cellular level let alone what effect it might have at the subcellular level (e.g. dendrites). Here, we examine the effect of single-pulse TMS on dendritic activity in layer 5 pyramidal neurons of the somatosensory cortex using an optical fiber imaging approach. We find that TMS causes GABAB-mediated inhibition of sensory-evoked dendritic Ca(2+) activity. We conclude that TMS directly activates fibers within the upper cortical layers that leads to the activation of dendrite-targeting inhibitory neurons which in turn suppress dendritic Ca(2+) activity. This result implies a specificity of TMS at the dendritic level that could in principle be exploited for investigating these structures non-invasively.

  3. Drosophila Sensory Neurons Require Dscam for Dendritic Self Avoidance and Proper Dendritic Field Organization

    OpenAIRE

    Soba, Peter; Zhu, Sijun; Emoto, Kazuo; Younger, Susan; Yang, Shun-Jen; Yu, Hung-Hsiang; Lee, Tzumin; Jan, Lily Yeh; Jan, Yuh-Nung

    2007-01-01

    A neuron’s dendrites typically do not cross one another. This intrinsic self-avoidance mechanism ensures unambiguous processing of sensory or synaptic inputs. Moreover, some neurons respect the territory of others of the same type, a phenomenon known as tiling. Different types of neurons, however, often have overlapping dendritic fields. We found that Down’s syndrome Cell Adhesion Molecule (Dscam) is required for dendritic self-avoidance of all four classes of Drosophila dendritic arborizatio...

  4. Homophilic Dscam interactions control complex dendrite morphogenesis

    OpenAIRE

    Michael E Hughes; Bortnick, Rachel; Tsubouchi, Asako; Bäumer, Philipp; Kondo, Masahiro; Uemura, Tadashi; Schmucker, Dietmar

    2007-01-01

    The morphogenesis of complex dendritic fields requires highly specific patterning and dendrite-dendrite recognition mechanisms. Alternative splicing of the Drosophila cell surface receptor Dscam results in up to 38,016 different receptor isoforms and in vitro binding studies suggested that sequence variability in immunoglobulin-like ecto-domains determines the specificity of strictly homophilic interactions. We report that diverse Dscam receptors play an important role in controlling cell-int...

  5. Alcohol disrupts sleep homeostasis.

    Science.gov (United States)

    Thakkar, Mahesh M; Sharma, Rishi; Sahota, Pradeep

    2015-06-01

    Alcohol is a potent somnogen and one of the most commonly used "over the counter" sleep aids. In healthy non-alcoholics, acute alcohol decreases sleep latency, consolidates and increases the quality (delta power) and quantity of NREM sleep during the first half of the night. However, sleep is disrupted during the second half. Alcoholics, both during drinking periods and during abstinences, suffer from a multitude of sleep disruptions manifested by profound insomnia, excessive daytime sleepiness, and altered sleep architecture. Furthermore, subjective and objective indicators of sleep disturbances are predictors of relapse. Finally, within the USA, it is estimated that societal costs of alcohol-related sleep disorders exceeds $18 billion. Thus, although alcohol-associated sleep problems have significant economic and clinical consequences, very little is known about how and where alcohol acts to affect sleep. In this review, we have described our attempts to unravel the mechanism of alcohol-induced sleep disruptions. We have conducted a series of experiments using two different species, rats and mice, as animal models. We performed microdialysis, immunohistochemical, pharmacological, sleep deprivation and lesion studies which suggest that the sleep-promoting effects of alcohol may be mediated via alcohol's action on the mediators of sleep homeostasis: adenosine (AD) and the wake-promoting cholinergic neurons of the basal forebrain (BF). Alcohol, via its action on AD uptake, increases extracellular AD resulting in the inhibition of BF wake-promoting neurons. Since binge alcohol consumption is a highly prevalent pattern of alcohol consumption and disrupts sleep, we examined the effects of binge drinking on sleep-wakefulness. Our results suggest that disrupted sleep homeostasis may be the primary cause of sleep disruption observed following binge drinking. Finally, we have also shown that sleep disruptions observed during acute withdrawal, are caused due to impaired

  6. Hierarchical assembly of diphenylalanine into dendritic nanoarchitectures.

    Science.gov (United States)

    Han, Tae Hee; Oh, Jun Kyun; Lee, Gyoung-Ja; Pyun, Su-Il; Kim, Sang Ouk

    2010-09-01

    Highly ordered, multi-dimensional dendritic nanoarchitectures were created via self-assembly of diphenylalanine from an acidic buffer solution. The self-similarity of dendritic structures was characterized by examining their fractal dimensions with the box-counting method. The fractal dimension was determined to be 1.7, which demonstrates the fractal dimension of structures generated by diffusion limited aggregation on a two-dimensional substrate surface. By confining the dendritic assembly of diphenylalanine within PDMS microchannels, the self-similar dendritic growth could be hierarchically directed to create linearly assembled nanoarchitectures. Our approach offers a novel pathway for creating and directing hierarchical nanoarchitecture from biomolecular assembly. PMID:20605423

  7. Precipitation dendrites in turbulent pipe flows

    Science.gov (United States)

    Angheluta, Luiza; Hawkins, Christopher; Hammer, Øyvind; Jamtveit, Bjørn

    2013-04-01

    Surface precipitation in pipelines, as well as freezing in water pipes is of great concern in many industrial applications where scaling phenomena becomes a control problem of pipe-clogging or an efficiency reduction in transport. Flow blockage often occurs even when only a small fraction is deposited non-uniformly on the walls in the form of dendrites. Dendritic patterns are commonly encountered in surface precipitation from supersaturated solutions, e.g. calcite dendrites, as well as in solidification from undercooled liquids, e.g. freezing of water into ice dendrites. We explore the mathematical similarities between precipitation and freezing processes and, in particular, investigate the effect of fluid flow on the precipitation dendrites on pipe walls. We use a phase field approach to model surface growth coupled with a lattice Boltzmann method that simulates a channel flow at varying Reynolds number. The dendrites orientation and shape depend non-trivially on the ratio between advection and diffusion, i.e. the Peclet number, as well as the Reynolds number. Roughness induced vortices near growing dendrites at high flow rates further affect the branch splitting of dendrites. We show how the transport rate in a pipeline may depend on the different dendritic morphologies, and provide estimates for the flow conditions that correspond to most efficient transport regimes.

  8. Disrupting Vestibular Activity Disrupts Body Ownership.

    Science.gov (United States)

    Hoover, Adria E N; Harris, Laurence R

    2015-01-01

    People are more sensitive at detecting asynchrony between a self-generated movement and visual feedback concerning that movement when the movement is viewed from a first-person perspective. We call this the 'self-advantage' and interpret it as an objective measure of self. Here we ask if disruption of the vestibular system in healthy individuals affects the self-advantage. Participants performed finger movements while viewing their hand in a first-person ('self') or third-person ('other') perspective and indicated which of two periods (one with minimum delay and the other with an added delay of 33-264 ms) was delayed. Their sensitivity to the delay was calculated from the psychometric functions obtained. During the testing, disruptive galvanic vestibular stimulation (GVS) was applied in five-minute blocks interleaved with five minutes of no stimulation for a total of 40 min. We confirmed the self-advantage under no stimulation (31 ms). In the presence of disruptive GVS this advantage disappeared and there was no longer a difference in performance between perspectives. The threshold delay for the 'other' perspective was not affected by the GVS. These results suggest that an intact vestibular signal is required to distinguish 'self' from 'other' and to maintain a sense of body ownership. PMID:26595957

  9. Endocrine disrupting chemicals

    DEFF Research Database (Denmark)

    Mandrup, Karen

    . To improve knowledge on possible influences of endocrine disrupters on female reproductive system, the effects of EDCs on genital malformations in females and the development of mammary glands were studied in the present project. AIMS: The aims for the studies on male and female mammary gland development......BACKGROUND: Endocrine disrupting chemicals (EDCs) may contribute to reproductive changes in boys in the Western world, however, less is known about influence of EDCs in women. The incidence of precocious breast development is increasing in USA and Europe and mammary gland development has been...... suggested as particularly sensitive to endocrine disruption. Mammary gland examination in toxicological studies may be useful for improving knowledge on possible influences of EDCs on human mammary glands and also be useful for detection of endocrine disrupting effects of chemicals as part of safety testing...

  10. Search and Disrupt

    DEFF Research Database (Denmark)

    Ørding Olsen, Anders

    This paper analyzes how external search is affected by strategic interest alignment among knowledge sources. I focus on misalignment arising from the heterogeneous effects of disruptive technologies by analyzing the influence of incumbents on 2,855 non-incumbents? external knowledge search efforts....... The efforts most likely to solve innovation problems obtained funding from the European Commission?s 7th Framework Program (2007-2013). The results show that involving incumbents improves search in complementary technologies, while demoting it when strategic interests are misaligned in disruptive technologies....... However, incumbent sources engaged in capability reconfiguration to accommodate disruption improve search efforts in disruptive technologies. The paper concludes that the value of external sources is contingent on more than their knowledge. Specifically, interdependence of sources in search gives rise...

  11. Fast generation of dendritic cells

    DEFF Research Database (Denmark)

    Kvistborg, P; Bøgh, Marie; Claesson, M H;

    2009-01-01

    Dendritic cells (DC) are potent antigen presenting cells capable of inducing immune responses. DC are widely used as vaccine adjuvant in experimental clinical settings. DC-based vaccines are normally generated using a standard 8day DC protocol (SDDC). In attempts to shorten the vaccine production...... SDDC to the IL-10 inducing stimulus of TLR ligands (R848 and LPS). Thus to determine the clinical relevance of fast DC protocols in cancer settings, small phase I trials should be conducted monitoring regulatory T cells carefully....

  12. Renal dendritic cells: an update

    OpenAIRE

    Velázquez, Peter; Dustin, Michael L.; Peter J Nelson

    2009-01-01

    Discovery into the role of renal dendritic cells (rDCs) in health and disease of the kidney is rapidly accelerating. Progress in deciphering DC precursors and the heterogeneity of monocyte subsets in mice and humans are providing insights into the biology of rDCs. Recent findings have extended knowledge of the origins, anatomy, and function of the rDC network at steady-state and during periods of injury to the renal parenchyma. This brief review highlights these new findings and provides an u...

  13. In vivo dendrite regeneration after injury is different from dendrite development.

    Science.gov (United States)

    Thompson-Peer, Katherine L; DeVault, Laura; Li, Tun; Jan, Lily Yeh; Jan, Yuh Nung

    2016-08-01

    Neurons receive information along dendrites and send signals along axons to synaptic contacts. The factors that control axon regeneration have been examined in many systems, but dendrite regeneration has been largely unexplored. Here we report that, in intact Drosophila larvae, a discrete injury that removes all dendrites induces robust dendritic growth that recreates many features of uninjured dendrites, including the number of dendrite branches that regenerate and responsiveness to sensory stimuli. However, the growth and patterning of injury-induced dendrites is significantly different from uninjured dendrites. We found that regenerated arbors cover much less territory than uninjured neurons, fail to avoid crossing over other branches from the same neuron, respond less strongly to mechanical stimuli, and are pruned precociously. Finally, silencing the electrical activity of the neurons specifically blocks injury-induced, but not developmental, dendrite growth. By elucidating the essential features of dendrites grown in response to acute injury, our work builds a framework for exploring dendrite regeneration in physiological and pathological conditions. PMID:27542831

  14. Recrystallization phenomena of solution grown paraffin dendrites

    NARCIS (Netherlands)

    Hollander, F.F.A.; Stasse, O.; Suchtelen, van J.; Enckevort, van W.J.P.

    2001-01-01

    Paraffin crystals were grown from decane solutions using a micro-Bridgman set up for in-situ observation of the morphology at the growth front. It is shown that for large imposed velocities, dendrites are obtained. After dendritic growth, aging or recrystallization processes set in rather quickly, c

  15. Vertical solidification of dendritic binary alloys

    Science.gov (United States)

    Heinrich, J. C.; Felicelli, S.; Poirier, D. R.

    1991-01-01

    Three numerical techniques are employed to analyze the influence of thermosolutal convection on defect formation in directionally solidified (DS) alloys. The finite-element models are based on the Boussinesq approximation and include the plane-front model and two plane-front models incorporating special dendritic regions. In the second model the dendritic region has a time-independent volume fraction of liquid, and in the last model the dendritic region evolves as local conditions dictate. The finite-element models permit the description of nonlinear thermosolutal convection by treating the dendritic regions as porous media with variable porosities. The models are applied to lead-tin alloys including DS alloys, and severe segregation phenomena such as freckles and channels are found to develop in the DS alloys. The present calculations and the permeability functions selected are shown to predict behavior in the dendritic regions that qualitatively matches that observed experimentally.

  16. Engineering crystals of dendritic molecules.

    Science.gov (United States)

    Lukin, Oleg; Schubert, Dirk; Müller, Claudia M; Schweizer, W Bernd; Gramlich, Volker; Schneider, Julian; Dolgonos, Grygoriy; Shivanyuk, Alexander

    2009-07-01

    A detailed single-crystal X-ray study of conformationally flexible sulfonimide-based dendritic molecules with systematically varied molecular architectures was undertaken. Thirteen crystal structures reported in this work include 9 structures of the second-generation dendritic sulfonimides decorated with different aryl groups, 2 compounds bearing branches of both second and first generation, and 2 representatives of the first generation. Analysis of the packing patterns of 9 compounds bearing second-generation branches shows that despite their lack of strong directive functional groups there is a repeatedly reproduced intermolecular interaction mode consisting in an anchor-type packing of complementary second-generation branches of neighbouring molecules. The observed interaction tolerates a wide range of substituents in meta- and para-positions of the peripheral arylsulfonyl rings. Quantum chemical calculations of the molecule-molecule interaction energies agree at the qualitative level with the packing preferences found in the crystalline state. The calculations can therefore be used as a tool to rationalize and predict molecular structures with commensurate and non-commensurate branches for programming of different packing modes in crystal. PMID:19549870

  17. The disruption management model.

    Science.gov (United States)

    McAlister, James

    2011-10-01

    Within all organisations, business continuity disruptions present a set of dilemmas that managers may not have dealt with before in their normal daily duties. The disruption management model provides a simple but effective management tool to enable crisis management teams to stay focused on recovery in the midst of a business continuity incident. The model has four chronological primary headlines, which steer the team through a quick-time crisis decision-making process. The procedure facilitates timely, systematic, rationalised and justified decisions, which can withstand post-event scrutiny. The disruption management model has been thoroughly tested within an emergency services environment and is proven to significantly support clear and concise decision making in a business continuity context. PMID:22130341

  18. Changing circumstances, disrupting habits.

    Science.gov (United States)

    Wood, Wendy; Witt, Melissa Guerrero; Tam, Leona

    2005-06-01

    The present research investigated the mechanisms guiding habitual behavior, specifically, the stimulus cues that trigger habit performance. When usual contexts for performance change, habits cannot be cued by recurring stimuli, and performance should be disrupted. Thus, the exercising, newspaper reading, and TV watching habits of students transferring to a new university were found to survive the transfer only when aspects of the performance context did not change (e.g., participants continued to read the paper with others). In some cases, the disruption in habits also placed behavior under intentional control so that participants acted on their current intentions. Changes in circumstances also affected the favorability of intentions, but changes in intentions alone could not explain the disruption of habits. Furthermore, regardless of whether contexts changed, nonhabitual behavior was guided by intentions. PMID:15982113

  19. Emerging and Disruptive Technologies

    Science.gov (United States)

    2016-01-01

    Several emerging or disruptive technologies can be identified that might, at some point in the future, displace established laboratory medicine technologies and practices. These include increased automation in the form of robots, 3-D printing, technology convergence (e.g., plug-in glucose meters for smart phones), new point-of-care technologies (e.g., contact lenses with sensors, digital and wireless enabled pregnancy tests) and testing locations (e.g., Retail Health Clinics, new at-home testing formats), new types of specimens (e.g., cell free DNA), big biology/data (e.g., million genome projects), and new regulations (e.g., for laboratory developed tests). In addition, there are many emerging technologies (e.g., planar arrays, mass spectrometry) that might find even broader application in the future and therefore also disrupt current practice. One interesting source of disruptive technology may prove to be the Qualcomm Tricorder XPrize, currently in its final stages. PMID:27683538

  20. The disruption management model.

    Science.gov (United States)

    McAlister, James

    2011-10-01

    Within all organisations, business continuity disruptions present a set of dilemmas that managers may not have dealt with before in their normal daily duties. The disruption management model provides a simple but effective management tool to enable crisis management teams to stay focused on recovery in the midst of a business continuity incident. The model has four chronological primary headlines, which steer the team through a quick-time crisis decision-making process. The procedure facilitates timely, systematic, rationalised and justified decisions, which can withstand post-event scrutiny. The disruption management model has been thoroughly tested within an emergency services environment and is proven to significantly support clear and concise decision making in a business continuity context.

  1. Sustainable Disruption Management

    DEFF Research Database (Denmark)

    Vaaben, Bo Valdemar

    The world we live in is globalized. Goods are seldom made in the place where they are used or consumed, and we do increasingly travel to other countries for either business or pleasure. In our everyday lives we rely on well-functioning global transportations systems to continue the standard......, such as e.g. technical problems or congestions are also typical causes of delays. Returning a transportation system to its original plan of operation is referred to as Disruption Management. Disruptions are, however, not the only cause of concern to the transportation industry. Fuel is becoming...... when managing recovery from disruptions. The underlying work of this thesis is carried out as an industrial PhD project in co-operation with the company Jeppesen, which have the airline industry as its primary area of business and the maritime industry as its secondary area. For this reason the thesis...

  2. Search and Disrupt

    DEFF Research Database (Denmark)

    Ørding Olsen, Anders

    Extant research on external knowledge search and open innovation assumes that collaborators are aligned in their strategic interests towards solving innovation problems. However, disruptive innovation is known to threaten the competitive advantage of incumbent firms, thereby creating a potential...... conflict of interest between these firms and their collaborators. This paper explores the extent to which strategic interests influence joint problem solving in both complementary and disruptive technologies by analyzing the effects of incumbent collaboration. The analysis disentangles inability...... and strategic intent to find that non-incumbents experience suppression of problem solving likelihood within disruptive technologies when incumbent collaborators are not strategically committed. The paper contributes to extant theory by showing the influence of firms’ underlying strategic interests...

  3. Interruptions disrupt reading comprehension.

    Science.gov (United States)

    Foroughi, Cyrus K; Werner, Nicole E; Barragán, Daniela; Boehm-Davis, Deborah A

    2015-06-01

    Previous research suggests that being interrupted while reading a text does not disrupt the later recognition or recall of information from that text. This research is used as support for Ericsson and Kintsch's (1995) long-term working memory (LT-WM) theory, which posits that disruptions while reading (e.g., interruptions) do not impair subsequent text comprehension. However, to fully comprehend a text, individuals may need to do more than recognize or recall information that has been presented in the text at a later time. Reading comprehension often requires individuals to connect and synthesize information across a text (e.g., successfully identifying complex topics such as themes and tones) and not just make a familiarity-based decision (i.e., recognition). The goal for this study was to determine whether interruptions while reading disrupt reading comprehension when the questions assessing comprehension require participants to connect and synthesize information across the passage. In Experiment 1, interruptions disrupted reading comprehension. In Experiment 2, interruptions disrupted reading comprehension but not recognition of information from the text. In Experiment 3, the addition of a 15-s time-out prior to the interruption successfully removed these negative effects. These data suggest that the time it takes to process the information needed to successfully comprehend text when reading is greater than that required for recognition. Any interference (e.g., an interruption) that occurs during the comprehension process may disrupt reading comprehension. This evidence supports the need for transient activation of information in working memory for successful text comprehension and does not support LT-WM theory. PMID:25867225

  4. Impact of dendritic size and dendritic topology on burst firing in pyramidal cells.

    Directory of Open Access Journals (Sweden)

    Ronald A J van Elburg

    2010-05-01

    Full Text Available Neurons display a wide range of intrinsic firing patterns. A particularly relevant pattern for neuronal signaling and synaptic plasticity is burst firing, the generation of clusters of action potentials with short interspike intervals. Besides ion-channel composition, dendritic morphology appears to be an important factor modulating firing pattern. However, the underlying mechanisms are poorly understood, and the impact of morphology on burst firing remains insufficiently known. Dendritic morphology is not fixed but can undergo significant changes in many pathological conditions. Using computational models of neocortical pyramidal cells, we here show that not only the total length of the apical dendrite but also the topological structure of its branching pattern markedly influences inter- and intraburst spike intervals and even determines whether or not a cell exhibits burst firing. We found that there is only a range of dendritic sizes that supports burst firing, and that this range is modulated by dendritic topology. Either reducing or enlarging the dendritic tree, or merely modifying its topological structure without changing total dendritic length, can transform a cell's firing pattern from bursting to tonic firing. Interestingly, the results are largely independent of whether the cells are stimulated by current injection at the soma or by synapses distributed over the dendritic tree. By means of a novel measure called mean electrotonic path length, we show that the influence of dendritic morphology on burst firing is attributable to the effect both dendritic size and dendritic topology have, not on somatic input conductance, but on the average spatial extent of the dendritic tree and the spatiotemporal dynamics of the dendritic membrane potential. Our results suggest that alterations in size or topology of pyramidal cell morphology, such as observed in Alzheimer's disease, mental retardation, epilepsy, and chronic stress, could change

  5. Fate mapping of dendritic cells

    Directory of Open Access Journals (Sweden)

    Barbara Ursula Schraml

    2015-05-01

    Full Text Available Dendritic cells (DCs are a heterogeneous group of mononuclear phagocytes with versatile roles in immunity. They are classified predominantly based on phenotypic and functional properties, namely their stellate morphology, expression of the integrin CD11c and major histocompatibility class II molecules, as well as their superior capacity to migrate to secondary lymphoid organs and stimulate naïve T cells. However, these attributes are not exclusive to DCs and often change within inflammatory or infectious environments. This led to debates over cell identification and questioned even the mere existence of DCs as distinct leukocyte lineage. Here, we review experimental approaches taken to fate map DCs and discuss how these have shaped our understanding of DC ontogeny and lineage affiliation. Considering the ontogenetic properties of DCs will help to overcome the inherent shortcomings of purely phenotypic- and function-based approaches to cell definition and will yield a more robust way of DC classification.

  6. Dendritic Cells for Anomaly Detection

    CERN Document Server

    Greensmith, Julie; Aickelin, Uwe

    2010-01-01

    Artificial immune systems, more specifically the negative selection algorithm, have previously been applied to intrusion detection. The aim of this research is to develop an intrusion detection system based on a novel concept in immunology, the Danger Theory. Dendritic Cells (DCs) are antigen presenting cells and key to the activation of the human signals from the host tissue and correlate these signals with proteins know as antigens. In algorithmic terms, individual DCs perform multi-sensor data fusion based on time-windows. The whole population of DCs asynchronously correlates the fused signals with a secondary data stream. The behaviour of human DCs is abstracted to form the DC Algorithm (DCA), which is implemented using an immune inspired framework, libtissue. This system is used to detect context switching for a basic machine learning dataset and to detect outgoing portscans in real-time. Experimental results show a significant difference between an outgoing portscan and normal traffic.

  7. Disruptive Co-Creation?

    DEFF Research Database (Denmark)

    Butler, Ivan; Christensen, David

    set up to foster innovative partnerships between civil society organizations, businesses and academia with the objective of supporting disruptive business model innovation in co-creation processes across these sectors. This paper delves into state-of-the-art concerning literature pertinent...

  8. Macrophage and dendritic cell subsets in IBD: ALDH+ cells are reduced in colon tissue of patients with ulcerative colitis regardless of inflammation

    DEFF Research Database (Denmark)

    Magnusson, M. K.; Brynjólfsson, S. F.; Dige, A.;

    2016-01-01

    Disruption of the homeostatic balance of intestinal dendritic cells (DCs) and macrophages (MQs) may contribute to inflammatory bowel disease. We characterized DC and MQ populations, including their ability to produce retinoic acid, in clinical material encompassing Crohn’s ileitis, Crohn’s coliti...

  9. DEX-1 and DYF-7 establish sensory dendrite length by anchoring dendritic tips during cell migration

    OpenAIRE

    Heiman, Maxwell G.; Shaham, Shai

    2009-01-01

    Cells are devices whose structures delimit function. For example, in the nervous system, neuronal and glial shapes dictate paths of information flow. To understand how cells acquire their shapes, we examined the formation of a sense organ in C. elegans. Using time-lapse imaging, we found that sensory dendrites form by stationary anchoring of dendritic tips during cell-body migration. A genetic screen identified DEX-1 and DYF-7, extracellular proteins required for dendritic tip anchoring, whic...

  10. Artificial Dendritic Cells: Multi-faceted Perspectives

    CERN Document Server

    Greensmith, Julie

    2009-01-01

    Dendritic cells are the crime scene investigators of the human immune system. Their function is to correlate potentially anomalous invading entities with observed damage to the body. The detection of such invaders by dendritic cells results in the activation of the adaptive immune system, eventually leading to the removal of the invader from the host body. This mechanism has provided inspiration for the development of a novel bio-inspired algorithm, the Dendritic Cell Algorithm. This algorithm processes information at multiple levels of resolution, resulting in the creation of information granules of variable structure. In this chapter we examine the multi-faceted nature of immunology and how research in this field has shaped the function of the resulting Dendritic Cell Algorithm. A brief overview of the algorithm is given in combination with the details of the processes used for its development. The chapter is concluded with a discussion of the parallels between our understanding of the human immune system a...

  11. Free energy and dendritic self-organisation

    Directory of Open Access Journals (Sweden)

    Stefan J Kiebel

    2011-10-01

    Full Text Available In this paper, we pursue recent observations that, through selective dendritic filtering, single neurons respond to specific sequences of presynaptic inputs. We try to provide a principled and mechanistic account of this selectivity by applying the free energy principle to a dendrite that is immersed in its neuropil or environment. We assume that neurons self-organize to minimise a free energy bound on the self-information or surprise of presynaptic inputs that are sampled. We model this as a selective pruning of dendritic spines that are expressed on a dendritic branch. This pruning occurs when the optimized postsynaptic gain falls below a threshold. Crucially, postsynaptic gain is itself optimized with respect to free energy. Pruning suppresses free energy as the dendrite selects presynaptic signals that conform to its expectations, specified by a generative model implicit in its intracellular kinetics. Not only does this provide a principled account of how neurons organize and selectively sample the myriad of potential presynaptic inputs they are exposed to, but it also connects the optimization of elemental neuronal (dendritic processing to generic (surprise or evidence-based schemes in statistics and machine learning, such as Bayesian model selection and automatic relevance determination.

  12. Endocrine disrupting compounds

    DEFF Research Database (Denmark)

    Bøgh, I B; Christensen, P; Dantzer, V;

    2001-01-01

    With the growing concern that environmental chemicals might impair human and animal fertility, it is important to investigate the possible influence of these substances on sexual differentiation and genital development of mammals. Many of these substances are suspected to interfere with endocrine...... processes, and exposure during critical periods of prenatal development might affect reproductive performance over several generations. Alkylphenols and their metabolites are lipophilic substances exerting apparent estrogenic action in in vitro and in vivo testing systems. With the widespread industrial use...... or embryo models for the evaluation of possible consequences of human exposure to endocrine disrupting compounds is discussed. Furthermore, possible consequences of exposure to endocrine disrupting compounds for the embryo transfer industry are addressed....

  13. Celibacy and Family Disruption

    OpenAIRE

    Emaletdinov B. M.

    2013-01-01

    Causes for celibacy, divorces and successful marriage are discussed in the article. Absence of true love and inability to build and keep it are the main reasons for family disruption. Amorousness, immature love and various forms of false or flawed love substitute the true feeling. It is caused by increased women’s independence, loss of mutual understanding and trust (due to infidelity or jealousy), incompatibility of characters or values. Celibacy is often conditioned by physical disability, ...

  14. Search and Disrupt

    OpenAIRE

    Ørding Olsen, Anders

    2015-01-01

    This paper analyzes how external search is affected by strategic interest alignment among knowledge sources. I focus on misalignment arising from the heterogeneous effects of disruptive technologies by analyzing the influence of incumbents on 2,855 non-incumbents? external knowledge search efforts. The efforts most likely to solve innovation problems obtained funding from the European Commission?s 7th Framework Program (2007-2013). The results show that involving incumbents improv...

  15. Schematically disruptive game design

    OpenAIRE

    Howell, Peter

    2011-01-01

    Many games focus their resources at satiating player ‘needs’, and meeting perceived expectations that players have of how games should behave and of what constitutes enjoyable, gratifying gameplay. This paper outlines an alternate position on game design – one which focuses on disrupting these expectations, on designing games that players cannot succeed in simply by relying on their pre-acquired gameplay experiences. A critique of current game design trends is offered, and possible future out...

  16. In Situ Observation of Cell-to-Dendrite Transition

    Institute of Scientific and Technical Information of China (English)

    PAN Xiu-Hong; HONG Yong; JIN Wei-Qing

    2005-01-01

    @@ The cell-to-dendrite transition of succinonitrile melt suspended on a loop-shaped Pt heater is observed in real time by a differential interference microscope coupled with Schlieren technique. The transition is divided into two parts: a dendrite coalition process and a subsequent dendrite elimination process. Firstly the dendrites from the same cell are united into a single dendrite. Secondly the competitive growth of dendrites from different cells leads to the elimination of dendrites. The two processes can be understood when involving crystallographic orientation. In addition, the tip velocity and primary spacing of a cell/dendrite are also measured. It turns out that the primary spacing has a significant jump, whereas the growth velocity has no abrupt change during the cell-to-dendrite transition.

  17. Targeting vaccines to dendritic cells.

    Science.gov (United States)

    Foged, Camilla; Sundblad, Anne; Hovgaard, Lars

    2002-03-01

    Dendritic cells (DC) are specialized antigen presenting cells (APC) with a remarkable ability to take up antigens and stimulate major histocompatibility complex (MHC)-restricted specific immune responses. Recent discoveries have shown that their role in initiating primary immune responses seems to be far superior to that of B-cells and macrophages. DC are localized at strategic places in the body at sites used by pathogens to enter the organism, and are thereby in an optimal position to capture antigens. In general, vaccination strategies try to mimic the invasiveness of the pathogens. DC are considered to play a central role for the provocation of primary immune responses by vaccination. A rational way of improving the potency and safety of new and already existing vaccines could therefore be to direct vaccines specifically to DC. There is a need for developing multifunctional vaccine drug delivery systems (DDS) with adjuvant effect that target DC directly and induce optimal immune responses. This paper will review the current knowledge of DC physiology as well as the progress in the field of novel vaccination strategies that directly or indirectly aim at targeting DC.

  18. Disruption - Access cards service

    CERN Multimedia

    2014-01-01

    We would like to inform you that between 10 November and 15 December 2014, the access cards service in Building 55 will be disrupted, as the GS Department has decided to improve the facilities for users of this building. During the work, you will find the registration, biometric registration and dosimeter exchange services on the second floor of Building 55 and the vehicle sticker service on the ground floor along with the access cards service. We thank you for your understanding and apologise for any inconvenience caused.

  19. Celibacy and Family Disruption

    Directory of Open Access Journals (Sweden)

    Emaletdinov B. M.

    2013-01-01

    Full Text Available Causes for celibacy, divorces and successful marriage are discussed in the article. Absence of true love and inability to build and keep it are the main reasons for family disruption. Amorousness, immature love and various forms of false or flawed love substitute the true feeling. It is caused by increased women’s independence, loss of mutual understanding and trust (due to infidelity or jealousy, incompatibility of characters or values. Celibacy is often conditioned by physical disability, revaluation of freedom and independence, huge requirements to partners, consumer attitude to life, infertility, alcohol and drug abuse, abnormalities in personality and sexuality.

  20. Dendrites Inhibition in Rechargeable Lithium Metal Batteries

    Science.gov (United States)

    Aryanfar, Asghar

    The specific high energy and power capacities of rechargeable lithium metal (Li0) batteries are ideally suited to portable devices and are valuable as storage units for intermittent renewable energy sources. Lithium, the lightest and most electropositive metal, would be the optimal anode material for rechargeable batteries if it were not for the fact that such devices fail unexpectedly by short-circuiting via the dendrites that grow across electrodes upon recharging. This phenomenon poses a major safety issue because it triggers a series of adverse events that start with overheating, potentially followed by the thermal decomposition and ultimately the ignition of the organic solvents used in such devices. In this thesis, we developed experimental platform for monitoring and quantifying the dendrite populations grown in a Li battery prototype upon charging under various conditions. We explored the effects of pulse charging in the kHz range and temperature on dendrite growth, and also on loss capacity into detached "dead" lithium particles. Simultaneously, we developed a computational framework for understanding the dynamics of dendrite propagation. The coarse-grained Monte Carlo model assisted us in the interpretation of pulsing experiments, whereas MD calculations provided insights into the mechanism of dendrites thermal relaxation. We also developed a computational framework for measuring the dead lithium crystals from the experimental images.

  1. Relativistic tidal disruption events

    Directory of Open Access Journals (Sweden)

    Levan A.

    2012-12-01

    Full Text Available In March 2011 Swift detected an extremely luminous and long-lived outburst from the nucleus of an otherwise quiescent, low luminosity (LMC-like galaxy. Named Swift J1644+57, its combination of high-energy luminosity (1048 ergs s−1 at peak, rapid X-ray variability (factors of >100 on timescales of 100 seconds and luminous, rising radio emission suggested that we were witnessing the birth of a moderately relativistic jet (Γ ∼ 2 − 5, created when a star is tidally disrupted by the supermassive black hole in the centre of the galaxy. A second event, Swift J2058+0516, detected two months later, with broadly similar properties lends further weight to this interpretation. Taken together this suggests that a fraction of tidal disruption events do indeed create relativistic outflows, demonstrates their detectability, and also implies that low mass galaxies can host massive black holes. Here, I briefly outline the observational properties of these relativistic tidal flares observed last year, and their evolution over the first year since their discovery.

  2. Disruptions in the TFTR tokamak

    International Nuclear Information System (INIS)

    For a successful reactor, it will be useful to predict the occurrence of disruptions and to understand disruption effects including how a plasma disrupts onto the wall and how reproducibly it does so. Studies of disruptions on TFTR at both high-βpol and high-density have shown that, in both types, a fast growing m/n=1/1 mode plays an important role. In highdensity disruptions, a newly observed fast m/n = 1/1 mode occurs early in the thermal decay phase. For the first time in TFTR q-profile measurements just prior to disruptions have been made. Experimental studies of heat deposition patterns on the first wall of TFTR due to disruptions have provided information on MHD phenomena prior to or during the disruption, how the energy is released to the wall, and the reproducibility of the heat loads from disruptions. This information is important in the design of future devices such as ITER. Several new processes of runaway electron generation are theoretically suggested and their application to TFTR and ITER is considered, together with a preliminary assessment of x-ray data from runaways generated during disruptions

  3. Detecting Danger: The Dendritic Cell Algorithm

    CERN Document Server

    Greensmith, Julie; Cayzer, Steve

    2010-01-01

    The Dendritic Cell Algorithm (DCA) is inspired by the function of the dendritic cells of the human immune system. In nature, dendritic cells are the intrusion detection agents of the human body, policing the tissue and organs for potential invaders in the form of pathogens. In this research, and abstract model of DC behaviour is developed and subsequently used to form an algorithm, the DCA. The abstraction process was facilitated through close collaboration with laboratory- based immunologists, who performed bespoke experiments, the results of which are used as an integral part of this algorithm. The DCA is a population based algorithm, with each agent in the system represented as an 'artificial DC'. Each DC has the ability to combine multiple data streams and can add context to data suspected as anomalous. In this chapter the abstraction process and details of the resultant algorithm are given. The algorithm is applied to numerous intrusion detection problems in computer security including the detection of p...

  4. Single dendrite-targeting interneurons generate branch-specific inhibition.

    Directory of Open Access Journals (Sweden)

    Caleb eStokes

    2014-11-01

    Full Text Available Microcircuits composed of dendrite-targeting inhibitory interneurons and pyramidal cells are fundamental elements of cortical networks, however, the impact of individual interneurons on pyramidal dendrites is unclear. Here, we combine paired recordings and calcium imaging to determine the spatial domain over which single dendrite-targeting interneurons influence pyramidal cells in olfactory cortex. We show that a major action of individual interneurons is to inhibit dendrites in a branch-specific fashion.

  5. Seaweed to dendrite transition in directional solidification.

    Science.gov (United States)

    Provatas, Nikolas; Wang, Quanyong; Haataja, Mikko; Grant, Martin

    2003-10-10

    We simulate directional solidification using a phase-field model solved with adaptive mesh refinement. For small surface tension anisotropy directed at 45 degrees relative to the pulling direction we observe a crossover from a seaweed to a dendritic morphology as the thermal gradient is lowered, consistent with recent experimental findings. We show that the morphology of crystal structures can be unambiguously characterized through the local interface velocity distribution. We derive semiempirically an estimate for the crossover from seaweed to dendrite as a function of thermal gradient and pulling speed.

  6. Sequence learning in differentially activated dendrites

    DEFF Research Database (Denmark)

    Nielsen, Bjørn Gilbert

    2003-01-01

    Differentially activated areas of a dendrite permit the existence of zones with distinct rates of synaptic modification, and such areas can be individually accessed using a reference signal which localizes synaptic plasticity and memory trace retrieval to certain subregions of the dendrite. It is...... to participate in multiple sequences, which can be learned without suffering from the 'wash-out' of synaptic efficacy associated with superimposition of training patterns. This is a biologically plausible solution to the stability-plasticity dilemma of learning in neural networks....

  7. Disruptive camouflage impairs object recognition

    OpenAIRE

    Richard J. Webster; Hassall, Christopher; Herdman, Chris M.; Godin, Jean-Guy J.; Sherratt, Thomas N.

    2013-01-01

    Whether hiding from predators, or avoiding battlefield casualties, camouflage is widely employed to prevent detection. Disruptive coloration is a seemingly well-known camouflage mechanism proposed to function by breaking up an object's salient features (for example their characteristic outline), rendering objects more difficult to recognize. However, while a wide range of animals are thought to evade detection using disruptive patterns, there is no direct experimental evidence that disruptive...

  8. The bHLH-PAS protein Spineless is necessary for the diversification of dendrite morphology of Drosophila dendritic arborization neurons

    OpenAIRE

    Kim, Michael D.; Jan, Lily Yeh; Jan, Yuh Nung

    2006-01-01

    Dendrites exhibit a wide range of morphological diversity, and their arborization patterns are critical determinants of proper neural connectivity. How different neurons acquire their distinct dendritic branching patterns during development is not well understood. Here we report that Spineless (Ss), the Drosophila homolog of the mammalian aryl hydrocarbon (dioxin) receptor (Ahr), regulates dendrite diversity in the dendritic arborization (da) sensory neurons. In loss-of-function ss mutants, c...

  9. Antigen dynamics of follicular dendritic cells

    NARCIS (Netherlands)

    Heesters, B.A.

    2015-01-01

    Stromal-derived follicular dendritic cells (FDCs) are a major depot for antigen that are essential for formation of germinal centers, the site where memory and effector B cells differentiate and high-affinity antibody production takes place. Historically, FDCs have been characterized as ‘accessory’

  10. Dendritic cells modified by vitamin D

    DEFF Research Database (Denmark)

    Pedersen, Ayako Wakatsuki; Claesson, Mogens Helweg; Zocca, Mai-Britt

    2011-01-01

    Dendritic cells (DCs), the most potent antigen-presenting cells of the immune system, express nuclear receptors for 1,25-dihydroxyvitamin D(3) (VD3) and they are one of its main targets. In the presence of VD3, DCs differentiate into a phenotype that resembles semimature DCs, with reduced T cell...

  11. Skin Dendritic Cells in Burn Patients

    OpenAIRE

    D’Arpa, N.; D’Amelio, L.; Accardo-Palumbo, A.; Pileri, D.; Mogavero, R.; Amato, G.; Napoli, B.; Alessandro, G.; Lombardo, C.; F. Conte

    2009-01-01

    The body's immunological response to burn injury has been a subject of great inquiry in recent years. Burn injury disturbs the immune system, resulting in a progressive suppression of the immune response that is thought to contribute to the development of sepsis. Dendritic cells (DCs) are potent antigen-presenting cells that possess the ability to stimulate naïve T cells.

  12. Dendritic cells in peripheral tolerance and immunity

    DEFF Research Database (Denmark)

    Gad, Monika; Claesson, Mogens Helweg; Pedersen, Anders Elm

    2003-01-01

    Dendritic cells capable of influencing immunity exist as functionally distinct subsets, T cell-tolerizing and T cell-immunizing subsets. The present paper reviews how these subsets of DCs develop, differentiate and function in vivo and in vitro at the cellular and molecular level. In particular, ...

  13. Generation of Immune Inhibitory Dendritic Cells and

    Directory of Open Access Journals (Sweden)

    Abediankenari Saeid

    2009-03-01

    Full Text Available Variety of positive as well as negative regulatory signals are provided by antigen presenting cell in particular by dendritic cells. In this research, we studied the capacity of dendritic cells to expand antigen-specific T regulatory cells.We also investigated the role of TGF-beta in induction inhibitory functions of dendritic cells in mixed leukocyte reactions.Dendritic cells were generated from blood CD14+ monocytes with granulocyte-Monocyte colony stimulating factor and interleukin-4 with or without TGF-beta (TGF-β-GM-DC or GM-DC. CD4+ T cell were isolated to assess lymphocyte proliferation by lymphocyte transformation test assay and the ratio of CD4+FOXp3+ CD25+ T cells were determined by fluorescene-activated cell sorter. T cell proliferation responses in GM-DC showed a significance antigen-specific proliferative response comparing with TGFβ-GM -DC. T Cell proliferation was inhibited in co-culture system containing DC-treated TGF-β. It can be suggested that the expsansion of T regulatory by TGF-β-GM-DC provides a means for antigen specific control of unwanted immune reactions.

  14. Critical overpotential for zinc dendrite formation

    Energy Technology Data Exchange (ETDEWEB)

    Popov, K.I.; Pavlovic, M.G.; Spasojevic, M.D.; Nakic, V.M.

    1979-07-01

    The critical overpotential for zinc dendrite growth is determined as 173 mV by the method described by Popov et al. This procedure can be applied successfully to metal deposition processes when there is a large codeposition of hydrogen. 4 figures.

  15. Localization of Vibrio vulnificus infection in dendritic cells and its effects on the cytoskeleton

    Institute of Scientific and Technical Information of China (English)

    WANG Zhi-gang; XU Shui-ling; SHAO Ping-yang; BAO Yi; CUI Ge; CAI Yu-jie

    2012-01-01

    Background Vibrio vulnificus (Vv) is an estuarine bacterium that can cause primary septicemia as well as serious wound infections.However,little is known about the mechanisms by which Vv infects dendritic cells (DCs) and its effects on cytoskeleton.In this study,we aimed to investigate the invasion,internalization,and the organelles damage of the cultured dendritic cells (a DC 2.4 strain) during Vv infection.Methods The study model was the cultured DCs infected by a Vv 1.758 strain.Electron microscopy was used to observe the localization of bacteria at the different time points of infection,cell morphology,and the process of organelles changes.The cytoskeleton structure including the microfilaments and the microtubules rearrangement was examined under a fluorescence microscope.Results The Vv were pinocytosised into the DC cells through double-sides,and localized at 1-2 μm of the inner side membrane.It took 1.3,1.9,and 3.4 hours to reach the infection ratio of 25%,50%,and 75%,respectively.Using electron microscopy,the DCs had been observed to have developed chromatin aggregation within 4.0 hours,and significant cytoskeleton structure disruption was noted within 6.0 hours.Conclusion The high lethality of Vv infection may be associated with the direct disruption of the DCs cytoskeleton structure.

  16. Model of Primary Austenite Dendrite Structure in Hypoeutectic Cast Iron

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The solidification of primary austenite in hypoeutectic gray cast iron was studied by stepped grinding and quantitative metallography. The dendrite structure of primary austenite can be described by three models: typical dendrite crystal model, metamorphic dendrite crystal model and network dendrite crystal model. The dendrite crystals formed according to 3rd model is much more than those formed according to other models in this experiment. The primary austenites are connected each other, and the primary stems of austenite could be regarded as secondary arms and vice versa.

  17. Numerical Simulations of Equiaxed Dendrite Growth Using Phase Field Method

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Phase field method offers the prospect of being able to perform realistic numerical experiments on dendrite growthin a metallic system. In this paper, the equiaxed dendrite evolution during the solidification of a pure material wasnumerically simulated using the phase field model. The equiaxed dendrite growth in a two-dimensional square domainof undercooled melt (nickel) with four-fold anisotropy was simulated. The phase field model equations was solvedusing the explicit finite difference method on a uniform mesh. The formation of various equiaxed dendrite patternswas shown by a series of simulations, and the effect of anisotropy on equiaxed dendrite morphology was investigated.

  18. DEX-1 and DYF-7 establish sensory dendrite length by anchoring dendritic tips during cell migration.

    Science.gov (United States)

    Heiman, Maxwell G; Shaham, Shai

    2009-04-17

    Cells are devices whose structures delimit function. For example, in the nervous system, neuronal and glial shapes dictate paths of information flow. To understand how cells acquire their shapes, we examined the formation of a sense organ in C. elegans. Using time-lapse imaging, we found that sensory dendrites form by stationary anchoring of dendritic tips during cell-body migration. A genetic screen identified DEX-1 and DYF-7, extracellular proteins required for dendritic tip anchoring, which act cooperatively at the time and place of anchoring. DEX-1 and DYF-7 contain, respectively, zonadhesin and zona pellucida domains, and DYF-7 self-associates into multimers important for anchoring. Thus, unlike other dendrites, amphid dendritic tips are positioned by DEX-1 and DYF-7 without the need for long-range guidance cues. In sequence and function, DEX-1 and DYF-7 resemble tectorins, which anchor stereocilia in the inner ear, suggesting that a sensory dendrite anchor may have evolved into part of a mechanosensor. PMID:19344940

  19. Repartnering after First Union Disruption

    Science.gov (United States)

    Wu, Zheng; Schimmele, Christoph M.

    2005-01-01

    Using data from the 1995 General Social Survey (N= 2,639), this study examines two competing repartnering choices made by Canadians after first union disruption: marriage or cohabitation. About 42% of women and 54% of men form a second union 5 years after union disruption, with cohabitation being the most prevalent choice. The timing of second…

  20. Disrupting Ethnography through Rhizoanalysis

    Directory of Open Access Journals (Sweden)

    Diana Masny

    2014-10-01

    Full Text Available This article interrogates principles of ethnography in education proposed by Mills and Morton: raw tellings, analytic pattern, vignette and empathy. This article adopts a position that is uncomfortable, unconventional and interesting. It involves a deterritorialization/ rupture of ethnography in education in order to reterritorialize a different concept: rhizoanalysis, a way to position theory and data that is multilayered, complex and messy. Rhizoanalysis, the main focus of this article is not a method. It is an approach to research conditioned by a reality in which Deleuze and Guattari disrupt representation, interpretation and subjectivity. In this article, Multiple Literacies Theory, a theoretical and practical framework, becomes a lens to examine a rhizomatic study of a Korean family recently arrived to Australia and attending English as a second language classes. Observations and interviews recorded the daily lives of the family. The vignettes were selected by reading data intensively and immanently through a process of palpation, an innovative approach to educational research. Rhizoanalysis proposes to abandon the given and invent different ways of thinking about and doing research and what might happen when reading data differently, intensively and immanently, through Multiple Literacies Theory. Rhizoanalysis, a game-changer in the way research can be conducted, affords a different lens to tackle issues in education through research.

  1. Tidal disruption event demographics

    Science.gov (United States)

    Kochanek, C. S.

    2016-09-01

    We survey the properties of stars destroyed in tidal disruption events (TDEs) as a function of black hole (BH) mass, stellar mass and evolutionary state, star formation history and redshift. For M_{BH} ≲ 10^7 M_{⊙}, the typical TDE is due to a M* ˜ 0.3 M⊙ M-dwarf, although the mass function is relatively flat for M_{ast } ≲ M_{⊙}. The contribution from older main-sequence stars and sub-giants is small but not negligible. From MBH ≃ 107.5-108.5 M⊙, the balance rapidly shifts to higher mass stars and a larger contribution from evolved stars, and is ultimately dominated by evolved stars at higher BH masses. The star formation history has little effect until the rates are dominated by evolved stars. TDE rates should decline very rapidly towards higher redshifts. The volumetric rate of TDEs is very high because the BH mass function diverges for low masses. However, any emission mechanism which is largely Eddington-limited for low BH masses suppresses this divergence in any observed sample and leads to TDE samples dominated by MBH ≃ 106.0-107.5 M⊙ BHs with roughly Eddington peak accretion rates. The typical fall-back time is relatively long, with 16 per cent having tfb plausible if tfb has any relation to the transient rise time. For almost any BH mass function, systematic searches for fainter, faster time-scale TDEs in smaller galaxies, and longer time-scale TDEs in more massive galaxies are likely to be rewarded.

  2. Asymmetry in signal propagation between the soma and dendrites plays a key role in determining dendritic excitability in motoneurons.

    Directory of Open Access Journals (Sweden)

    Hojeong Kim

    Full Text Available It is widely recognized that propagation of electrophysiological signals between the soma and dendrites of neurons differs depending on direction, i.e. it is asymmetric. How this asymmetry influences the activation of voltage-gated dendritic channels, and consequent neuronal behavior, remains unclear. Based on the analysis of asymmetry in several types of motoneurons, we extended our previous methodology for reducing a fully reconstructed motoneuron model to a two-compartment representation that preserved asymmetric signal propagation. The reduced models accurately replicated the dendritic excitability and the dynamics of the anatomical model involving a persistent inward current (PIC dispersed over the dendrites. The relationship between asymmetric signal propagation and dendritic excitability was investigated using the reduced models while varying the asymmetry in signal propagation between the soma and the dendrite with PIC density constant. We found that increases in signal attenuation from soma to dendrites increased the activation threshold of a PIC (hypo-excitability, whereas increases in signal attenuation from dendrites to soma decreased the activation threshold of a PIC (hyper-excitability. These effects were so strong that reversing the asymmetry in the soma-to-dendrite vs. dendrite-to-soma attenuation, reversed the correlation between PIC threshold and distance of this current source from the soma. We propose the tight relation of the asymmetric signal propagation to the input resistance in the dendrites as a mechanism underlying the influence of the asymmetric signal propagation on the dendritic excitability. All these results emphasize the importance of maintaining the physiological asymmetry in dendritic signaling not only for normal function of the cells but also for biophysically realistic simulations of dendritic excitability.

  3. When Disruptive Approaches Meet Disruptive Technologies: Learning at a Distance.

    Science.gov (United States)

    Gibson, Chere Campbell

    2000-01-01

    Reviews research on constructivism in learning and selection of learning strategies. Suggests linking constructivism with instructional technologies for continuing medical education in order to "disrupt" reactive, habitual ways of learning and encourage active engagement. (SK)

  4. Endocrine Effects of Circadian Disruption.

    Science.gov (United States)

    Bedrosian, Tracy A; Fonken, Laura K; Nelson, Randy J

    2016-01-01

    Disruption of circadian rhythms, provoked by artificial lighting at night, inconsistent sleep-wake schedules, and transmeridian air travel, is increasingly prevalent in modern society. Desynchrony of biological rhythms from environmental light cycles has dramatic consequences for human health. In particular, disrupting homeostatic oscillations in endocrine tissues and the hormones that these tissues regulate can have cascading effects on physiology and behavior. Accumulating evidence suggests that chronic disruption of circadian organization of endocrine function may lead to metabolic, reproductive, sleep, and mood disorders. This review discusses circadian control of endocrine systems and the consequences of distorting rhythmicity of these systems. PMID:26208951

  5. Sleeping dendrites: fiber-optic measurements of dendritic calcium activity in freely moving and sleeping animals

    Directory of Open Access Journals (Sweden)

    Julie Seibt

    2014-03-01

    Full Text Available Dendrites are the post-synaptic sites of most excitatory and inhibitory synapses in the brain, making them the main location of cortical information processing and synaptic plasticity. Although current hypotheses suggest a central role for sleep in proper cognitive function and brain plasticity, virtually nothing is known about changes in dendritic activity across the sleep-wake cycle and how waking experience modifies this activity. To start addressing these questions, we developed a method that allows long-term recordings of EEGs/EMG combined with in vivo cortical calcium (Ca2+ activity in freely moving and sleeping rats. We measured Ca2+ activity from populations of dendrites of layer (L 5 pyramidal neurons (n = 13 rats that we compared with Ca2+ activity from populations of neurons in L2/3 (n = 11 rats. L5 and L2/3 neurons were labelled using bolus injection of OGB1-AM or GCaMP6 (1. Ca2+ signals were detected using a fiber-optic system (cannula diameter = 400µm, transmitting the changes in fluorescence to a photodiode. Ca2+ fluctuations could then be correlated with ongoing changes in brain oscillatory activity during 5 major brain states: active wake [AW], quiet wake [QW], NREM, REM and NREM-REM transition (or intermediate state, [IS]. Our Ca2+ recordings show large transients in L5 dendrites and L2/3 neurons that oscillate predominantly at frequencies In summary, we show that this technique is successful in monitoring fluctuations in ongoing dendritic Ca2+ activity during natural brain states and allows, in principle, to combine behavioral measurement with imaging from various brain regions (e.g. deep structures in freely behaving animals. Using this method, we show that Ca2+ transients from populations of L2/3 neurons and L5 dendrites are deferentially regulated across the sleep/wake cycle, with dendritic activity being the highest during the IS sleep. Our correlation analysis suggests that specific sleep EEG activity during NREM and IS

  6. A Genome-Wide Screen for Dendritically Localized RNAs Identifies Genes Required for Dendrite Morphogenesis

    Directory of Open Access Journals (Sweden)

    Mala Misra

    2016-08-01

    Full Text Available Localizing messenger RNAs at specific subcellular sites is a conserved mechanism for targeting the synthesis of cytoplasmic proteins to distinct subcellular domains, thereby generating the asymmetric protein distributions necessary for cellular and developmental polarity. However, the full range of transcripts that are asymmetrically distributed in specialized cell types, and the significance of their localization, especially in the nervous system, are not known. We used the EP-MS2 method, which combines EP transposon insertion with the MS2/MCP in vivo fluorescent labeling system, to screen for novel localized transcripts in polarized cells, focusing on the highly branched Drosophila class IV dendritic arborization neurons. Of a total of 541 lines screened, we identified 55 EP-MS2 insertions producing transcripts that were enriched in neuronal processes, particularly in dendrites. The 47 genes identified by these insertions encode molecularly diverse proteins, and are enriched for genes that function in neuronal development and physiology. RNAi-mediated knockdown confirmed roles for many of the candidate genes in dendrite morphogenesis. We propose that the transport of mRNAs encoded by these genes into the dendrites allows their expression to be regulated on a local scale during the dynamic developmental processes of dendrite outgrowth, branching, and/or remodeling.

  7. Simulation of dendritic growth reveals necessary and sufficient parameters to describe the shapes of dendritic trees

    Science.gov (United States)

    Trottier, Olivier; Ganguly, Sujoy; Bowne-Anderson, Hugo; Liang, Xin; Howard, Jonathon

    For the last 120 years, the development of neuronal shapes has been of great interest to the scientific community. Over the last 30 years, significant work has been done on the molecular processes responsible for dendritic development. In our ongoing research, we use the class IV sensory neurons of the Drosophila melanogaster larva as a model system to understand the growth of dendritic arbors. Our main goal is to elucidate the mechanisms that the neuron uses to determine the shape of its dendritic tree. We have observed the development of the class IV neuron's dendritic tree in the larval stage and have concluded that morphogenesis is defined by 3 distinct processes: 1) branch growth, 2) branching and 3) branch retraction. As the first step towards understanding dendritic growth, we have implemented these three processes in a computational model. Our simulations are able to reproduce the branch length distribution, number of branches and fractal dimension of the class IV neurons for a small range of parameters.

  8. A Genome-Wide Screen for Dendritically Localized RNAs Identifies Genes Required for Dendrite Morphogenesis

    Science.gov (United States)

    Misra, Mala; Edmund, Hendia; Ennis, Darragh; Schlueter, Marissa A.; Marot, Jessica E.; Tambasco, Janet; Barlow, Ida; Sigurbjornsdottir, Sara; Mathew, Renjith; Vallés, Ana Maria; Wojciech, Waldemar; Roth, Siegfried; Davis, Ilan; Leptin, Maria; Gavis, Elizabeth R.

    2016-01-01

    Localizing messenger RNAs at specific subcellular sites is a conserved mechanism for targeting the synthesis of cytoplasmic proteins to distinct subcellular domains, thereby generating the asymmetric protein distributions necessary for cellular and developmental polarity. However, the full range of transcripts that are asymmetrically distributed in specialized cell types, and the significance of their localization, especially in the nervous system, are not known. We used the EP-MS2 method, which combines EP transposon insertion with the MS2/MCP in vivo fluorescent labeling system, to screen for novel localized transcripts in polarized cells, focusing on the highly branched Drosophila class IV dendritic arborization neurons. Of a total of 541 lines screened, we identified 55 EP-MS2 insertions producing transcripts that were enriched in neuronal processes, particularly in dendrites. The 47 genes identified by these insertions encode molecularly diverse proteins, and are enriched for genes that function in neuronal development and physiology. RNAi-mediated knockdown confirmed roles for many of the candidate genes in dendrite morphogenesis. We propose that the transport of mRNAs encoded by these genes into the dendrites allows their expression to be regulated on a local scale during the dynamic developmental processes of dendrite outgrowth, branching, and/or remodeling. PMID:27260999

  9. A Genome-Wide Screen for Dendritically Localized RNAs Identifies Genes Required for Dendrite Morphogenesis.

    Science.gov (United States)

    Misra, Mala; Edmund, Hendia; Ennis, Darragh; Schlueter, Marissa A; Marot, Jessica E; Tambasco, Janet; Barlow, Ida; Sigurbjornsdottir, Sara; Mathew, Renjith; Vallés, Ana Maria; Wojciech, Waldemar; Roth, Siegfried; Davis, Ilan; Leptin, Maria; Gavis, Elizabeth R

    2016-01-01

    Localizing messenger RNAs at specific subcellular sites is a conserved mechanism for targeting the synthesis of cytoplasmic proteins to distinct subcellular domains, thereby generating the asymmetric protein distributions necessary for cellular and developmental polarity. However, the full range of transcripts that are asymmetrically distributed in specialized cell types, and the significance of their localization, especially in the nervous system, are not known. We used the EP-MS2 method, which combines EP transposon insertion with the MS2/MCP in vivo fluorescent labeling system, to screen for novel localized transcripts in polarized cells, focusing on the highly branched Drosophila class IV dendritic arborization neurons. Of a total of 541 lines screened, we identified 55 EP-MS2 insertions producing transcripts that were enriched in neuronal processes, particularly in dendrites. The 47 genes identified by these insertions encode molecularly diverse proteins, and are enriched for genes that function in neuronal development and physiology. RNAi-mediated knockdown confirmed roles for many of the candidate genes in dendrite morphogenesis. We propose that the transport of mRNAs encoded by these genes into the dendrites allows their expression to be regulated on a local scale during the dynamic developmental processes of dendrite outgrowth, branching, and/or remodeling. PMID:27260999

  10. Dendritic nanocomposite for delivery of antibacterial agent

    Institute of Scientific and Technical Information of China (English)

    Pureti Madhu Kumar; PSrinivasa Babu; Shaik Rasheed; Ramadoss Karthikeyan

    2013-01-01

    Objective: To develop and explore the use of PEGylated poly (propylene imine) dendritic architecture for the delivery of an anti bacterial bioactive, Trimethoprim. Methods: For this study, PEGylated poly(propylene imine) dendritic architecture was synthesized and loaded with Trimethoprim and targeted to the resistant producing strains of both gram positive and gram negative. The antibacterial activity was carried out by agar well-diffusion method to compare zone of inhibition with standard drug and plain PPI dendrimer. Results: The study showed that the Trimethoprim loaded dendrimer has significant antibacterial activity than the plain PPI dendrimer, but standard drug was not shown zone of inhibition upon both microorganisms butKlebsiella pneumoniae (K. pneumoniae) the pure drug showed activity. Conclusions: In this study antibacterial activity of synthesized system is also relatively safer and holds potential to deliver any other antibacterial agent to the resistant producing strains.

  11. Sensitivity of Dendritic Cells to Microenvironment Signals

    Science.gov (United States)

    Motta, Juliana Maria; Rumjanek, Vivian Mary

    2016-01-01

    Dendritic cells are antigen-presenting cells capable of either activating the immune response or inducing and maintaining immune tolerance. They do this by integrating stimuli from the environment and changing their functional status as a result of plasticity. The modifications suffered by these cells have consequences in the way the organism may respond. In the present work two opposing situations known to affect dendritic cells are analyzed: tumor growth, leading to a microenvironment that favors the induction of a tolerogenic profile, and organ transplantation, which leads to a proinflammatory profile. Lessons learned from these situations may help to understand the mechanisms of modulation resulting not only from the above circumstances, but also from other pathologies. PMID:27088097

  12. Sensitivity of Dendritic Cells to Microenvironment Signals

    Directory of Open Access Journals (Sweden)

    Juliana Maria Motta

    2016-01-01

    Full Text Available Dendritic cells are antigen-presenting cells capable of either activating the immune response or inducing and maintaining immune tolerance. They do this by integrating stimuli from the environment and changing their functional status as a result of plasticity. The modifications suffered by these cells have consequences in the way the organism may respond. In the present work two opposing situations known to affect dendritic cells are analyzed: tumor growth, leading to a microenvironment that favors the induction of a tolerogenic profile, and organ transplantation, which leads to a proinflammatory profile. Lessons learned from these situations may help to understand the mechanisms of modulation resulting not only from the above circumstances, but also from other pathologies.

  13. Macrophage and dendritic cell subsets in IBD: ALDH+ cells are reduced in colon tissue of patients with ulcerative colitis regardless of inflammation

    OpenAIRE

    Maria K Magnusson; Brynjólfsson, Siggeir F; Dige, Anders; Uronen-Hansson, Heli; Börjesson, Lars G.; Bengtsson, Jonas L.; Gudjonsson, Sigurdur; Öhman, Lena; Agnholt, Jørgen; Sjövall, Henrik; Agace, William W; Wick, Mary Jo

    2015-01-01

    Disruption of the homeostatic balance of intestinal dendritic cells (DCs) and macrophages (MQs) may contribute to inflammatory bowel disease. We characterized DC and MQ populations, including their ability to produce retinoic acid, in clinical material encompassing Crohn’s ileitis, Crohn’s colitis and ulcerative colitis (UC) as well as mesenteric lymph nodes (MLNs) draining these sites. Increased CD14+DRint MQs characterized inflamed intestinal mucosa while total CD141+ or CD1c+ DCs numbers w...

  14. Neurotoxicity of Thyroid Disrupting Contaminants

    Science.gov (United States)

    Thyroid hormones playa critical role in the normal development ofthe mammalian brain. Thyroid disrupting chemicals (TDCs) are environmental contaminants that alter the structure or function ofthe thyroid gland, alter regulatory enzymes associated with thyroid hormone (TH) homeost...

  15. Vortex disruption by magnetohydrodynamic feedback

    CERN Document Server

    Mak, Julian; Hughes, D W

    2016-01-01

    In an electrically conducting fluid, vortices stretch out a weak, large-scale magnetic field to form strong current sheets on their edges. Associated with these current sheets are magnetic stresses, which are subsequently released through reconnection, leading to vortex disruption, and possibly even destruction. This disruption phenomenon is investigated here in the context of two-dimensional, homogeneous, incompressible magnetohydrodynamics. We derive a simple order of magnitude estimate for the magnetic stresses --- and thus the degree of disruption --- that depends on the strength of the background magnetic field (measured by the parameter $M$, a ratio between the Alfv\\'en speed and a typical flow speed) and on the magnetic diffusivity (measured by the magnetic Reynolds number $\\mbox{Rm}$). The resulting estimate suggests that significant disruption occurs when $M^{2}\\mbox{Rm} = O(1)$. To test our prediction, we analyse direct numerical simulations of vortices generated by the breakup of unstable shear flo...

  16. Pulmonary dendritic cells: thinking globally, acting locally

    OpenAIRE

    Randall, Troy D.

    2010-01-01

    The phrase “think globally, act locally” was coined in the early 1970s and directed individuals to clean up their local environment with the ultimate goal of improving the health of the entire planet. Several recent studies indicate that similar considerations apply to the immune system, in which small numbers of leukocytes, such as pulmonary dendritic cells, can modify the local immune environment in the lung and promote a positive outcome for the organism.

  17. Dendritic cells and aging: consequences for autoimmunity

    OpenAIRE

    Agrawal, Anshu; Sridharan, Aishwarya; Prakash, Sangeetha; Agrawal, Harsh

    2012-01-01

    The immune system has evolved to mount immune responses against foreign pathogens and to remain silent against self-antigens. A balance between immunity and tolerance is required as any disturbance may result in chronic inflammation or autoimmunity. Dendritic cells (DCs) actively participate in maintaining this balance. Under steady-state conditions, DCs remain in an immature state and do not mount an immune response against circulating self-antigens in the periphery, which maintains a state ...

  18. Imaging membrane potential in dendritic spines

    OpenAIRE

    Nuriya, Mutsuo; Jiang, Jiang; Nemet, Boaz; Eisenthal, Kenneth B.; Yuste, Rafael

    2006-01-01

    Dendritic spines mediate most excitatory inputs in the brain. Although it is clear that spines compartmentalize calcium, it is still unknown what role, if any, they play in integrating synaptic inputs. To investigate the electrical function of spines directly, we used second harmonic generation (SHG) imaging of membrane potential in pyramidal neurons from hippocampal cultures and neocortical brain slices. With FM 4-64 as an intracellular SHG chromophore, we imaged membrane potential in the so...

  19. Follicular dendritic cells in health and disease

    OpenAIRE

    El Shikh, Mohey Eldin M.; Costantino ePitzalis

    2012-01-01

    Follicular dendritic cells (FDCs) are unique immune cells that contribute to the regulation of humoral immune responses. These cells are located in the B cell follicles of secondary lymphoid tissues where they trap and retain antigens (Ags) in the form of highly immunogenic immune complexes (ICs) consisting of Ag plus specific antibody (Ab) and/or complement proteins. FDCs multimerise Ags and present them polyvalently to B cells in periodically arranged arrays that extensively crosslink the B...

  20. Follicular dendritic cells in health and disease

    OpenAIRE

    El Shikh, Mohey Eldin M.; Pitzalis, Costantino

    2012-01-01

    Follicular dendritic cells (FDCs) are unique immune cells that contribute to the regulation of humoral immune responses. These cells are located in the B-cell follicles of secondary lymphoid tissues where they trap and retain antigens (Ags) in the form of highly immunogenic immune complexes (ICs) consisting of Ag plus specific antibody (Ab) and/or complement proteins. FDCs multimerize Ags and present them polyvalently to B-cells in periodically arranged arrays that extensively crosslink the B...

  1. Role of Dendritic Cells in Immune Dysfunction

    Science.gov (United States)

    Savary, Cherylyn A.

    1997-01-01

    Specific aims include: (1) Application of the bioreactor to enhance cytokine-regulated proliferation and maturation of dendritic cells (DC); (2) Based on clues from spaceflight: compare the frequency and function of DC in normal donors and immunocompromised cancer patients; and (3) Initiate studies on the efficiency of cytokine therapy and DC-assisted immunotherapy (using bioreactor-expanded DC) in animal models of experimental fungal infections.

  2. Bacterial Probiotic Modulation of Dendritic Cells

    OpenAIRE

    Drakes, Maureen; Blanchard, Thomas; Czinn, Steven

    2004-01-01

    Intestinal dendritic cells are continually exposed to ingested microorganisms and high concentrations of endogenous bacterial flora. These cells can be activated by infectious agents and other stimuli to induce T-cell responses and to produce chemokines which recruit other cells to the local environment. Bacterial probiotics are of increasing use against intestinal disorders such as inflammatory bowel disease. They act as nonpathogenic stimuli within the gut to regain immunologic quiescence. ...

  3. Phosphorylation of β-Tubulin by the Down Syndrome Kinase, Minibrain/DYRK1a, Regulates Microtubule Dynamics and Dendrite Morphogenesis.

    Science.gov (United States)

    Ori-McKenney, Kassandra M; McKenney, Richard J; Huang, Hector H; Li, Tun; Meltzer, Shan; Jan, Lily Yeh; Vale, Ronald D; Wiita, Arun P; Jan, Yuh Nung

    2016-05-01

    Dendritic arborization patterns are consistent anatomical correlates of genetic disorders such as Down syndrome (DS) and autism spectrum disorders (ASDs). In a screen for abnormal dendrite development, we identified Minibrain (MNB)/DYRK1a, a kinase implicated in DS and ASDs, as a regulator of the microtubule cytoskeleton. We show that MNB is necessary to establish the length and cytoskeletal composition of terminal dendrites by controlling microtubule growth. Altering MNB levels disrupts dendrite morphology and perturbs neuronal electrophysiological activity, resulting in larval mechanosensation defects. Using in vivo and in vitro approaches, we uncover a molecular pathway whereby direct phosphorylation of β-tubulin by MNB inhibits tubulin polymerization, a function that is conserved for mammalian DYRK1a. Our results demonstrate that phosphoregulation of microtubule dynamics by MNB/DYRK1a is critical for dendritic patterning and neuronal function, revealing a previously unidentified mode of posttranslational microtubule regulation in neurons and uncovering a conserved pathway for a DS- and ASD-associated kinase. PMID:27112495

  4. Plasmacytoid dendritic cell role in cutaneous malignancies.

    Science.gov (United States)

    Saadeh, Dana; Kurban, Mazen; Abbas, Ossama

    2016-07-01

    Plasmacytoid dendritic cells (pDCs) correspond to a specialized dendritic cell population that exhibit plasma cell morphology, express CD4, CD123, HLA-DR, blood-derived dendritic cell antigen-2 (BDCA-2), and Toll-like receptor (TLR)7 and TLR9 within endosomal compartments. Through their production of type I interferons (IFNs) and other pro-inflammatory cytokines, pDCs provide anti-viral resistance and link the innate and adaptive immunity by controlling the function of myeloid DCs, lymphocytes, and natural killer (NK) cells. While lacking from normal skin, pDCs are usually recruited to the skin in several cutaneous pathologies where they appear to be involved in the pathogenesis of several infectious, inflammatory/autoimmune, and neoplastic entities. Among the latter group, pDCs have the potential to induce anti-tumour immunity; however, the complex interaction of pDCs with tumor cells and their micro-environment appears to contribute to immunologic tolerance. In this review, we aim at highlighting the role played by pDCs in cutaneous malignancies with special emphasis on the underlying mechanisms.

  5. The Isothermal Dendritic Growth Experiment Archive

    Science.gov (United States)

    Koss, Matthew

    2009-03-01

    The growth of dendrites is governed by the interplay between two simple and familiar processes---the irreversible diffusion of energy, and the reversible work done in the formation of new surface area. To advance our understanding of these processes, NASA sponsored a project that flew on the Space Shuttle Columbia is 1994, 1996, and 1997 to record and analyze benchmark data in an apparent-microgravity ``laboratory.'' In this laboratory, energy transfer by gravity driven convection was essentially eliminated and one could test independently, for the first time, both components of dendritic growth theory. The analysis of this data shows that although the diffusion of energy can be properly accounted for, the results from interfacial physics appear to be in disagreement and alternate models should receive increased attention. Unfortunately, currently and for the foreseeable future, there is no access or financial support to develop and conduct additional experiments of this type. However, the benchmark data of 35mm photonegatives, video, and all supporting instrument data are now available at the IDGE Archive at the College of the Holy Cross. This data may still have considerable relevance to researchers working specifically with dendritic growth, and more generally those working in the synthesis, growth & processing of materials, multiscale computational modeling, pattern formation, and systems far from equilibrium.

  6. Numerical Modeling of Dendrite Growth in Al Alloys

    Institute of Scientific and Technical Information of China (English)

    许庆彦; 柳百成

    2004-01-01

    Dendritic grains are the most often observed microstructure in metals and alloys. In the past decade, more and more attention has been paid to the modeling and simulation of dendritic microstructures. This paper describes a modified diffusion-limited aggregation model to simulate the complex shape of the dendrite grains during metal solidification. The fractal model was used to simulate equiaxed dendrite growth. The fractal dimensions of simulated Al alloy structures range from 1.63-1.88 which compares well with the experimentally-measured fractal dimension of 1.85; therefore, the model accurately predicts not only the dendritic structure morphology, but also the fractal dimension of the dendrite structure formed during solidification.

  7. Special fractal growth of dendrite copper using a hydrothermal method

    Science.gov (United States)

    Zheng, Yan; Zhang, Zhejuan; Guo, Pingsheng; He, Pingang; Sun, Zhuo

    2011-08-01

    Special fractal dendrite Cu nanostructures have been synthesized through a simple hydrothermal method, and the effects of the volume ratio between glycerol and water and the concentration of H 3PO 3 on the morphologies of dendrite Cu have been studied in detail. The Field emission scanning electron microscopy (FESEM), Transmission electron microscopy (TEM) and X-ray diffraction (XRD) have been used to characterize these Cu products. The results indicate that rhombic diamond and different morphologies of fractal dendrite were prepared because of the accumulation of Cu nuclei based on the diffusion-limited aggregation (DLA) and the nucleation-limited aggregation (NLA) model. Fortunately, symmetrical leaf-like dendrite Cu nanostructures different from Cu dendrites reported before have been obtained. Additionally, an explanation for the growth of fractal dendrite Cu has been discussed carefully.

  8. Molecular identity of dendritic voltage-gated sodium channels.

    Science.gov (United States)

    Lorincz, Andrea; Nusser, Zoltan

    2010-05-14

    Active invasion of the dendritic tree by action potentials (APs) generated in the axon is essential for associative synaptic plasticity and neuronal ensemble formation. In cortical pyramidal cells (PCs), this AP back-propagation is supported by dendritic voltage-gated Na+ (Nav) channels, whose molecular identity is unknown. Using a highly sensitive electron microscopic immunogold technique, we revealed the presence of the Nav1.6 subunit in hippocampal CA1 PC proximal and distal dendrites. Here, the subunit density is lower by a factor of 35 to 80 than that found in axon initial segments. A gradual decrease in Nav1.6 density along the proximodistal axis of the dendritic tree was also detected without any labeling in dendritic spines. Our results reveal the characteristic subcellular distribution of the Nav1.6 subunit, identifying this molecule as a key substrate enabling dendritic excitability. PMID:20466935

  9. Neural pattern formation in networks with dendritic structure

    Science.gov (United States)

    Bressloff, P. C.; De Souza, B.

    1998-04-01

    We present a detailed analysis of a recently proposed model of neural pattern formation that is based on the combined effect of diffusion along a neuron's dendritic tree and recurrent interactions along axo-dendritic synaptic connections. For concreteness, we consider a one-dimensional array of analog neurons with the dendritic tree idealized as a one-dimensional cable. Linear stability analysis and bifurcation theory together with numerical simulations are used to establish conditions for the onset of a Turing instability leading to the formation of stable spatial patterns of network output activity. It is shown that the presence of dendritic structure can induce dynamic (time-periodic) spatial pattern formation. Moreover, correlations between the dendritic location of a synapse and the relative positions of neurons in the network are shown to result in spatially oscillating patterns of activity along the dendrites of each neuron.

  10. Dendritic spine detection using curvilinear structure detector and LDA classifier.

    Science.gov (United States)

    Zhang, Yong; Zhou, Xiaobo; Witt, Rochelle M; Sabatini, Bernardo L; Adjeroh, Donald; Wong, Stephen T C

    2007-06-01

    Dendritic spines are small, bulbous cellular compartments that carry synapses. Biologists have been studying the biochemical pathways by examining the morphological and statistical changes of the dendritic spines at the intracellular level. In this paper a novel approach is presented for automated detection of dendritic spines in neuron images. The dendritic spines are recognized as small objects of variable shape attached or detached to multiple dendritic backbones in the 2D projection of the image stack along the optical direction. We extend the curvilinear structure detector to extract the boundaries as well as the centerlines for the dendritic backbones and spines. We further build a classifier using Linear Discriminate Analysis (LDA) to classify the attached spines into valid and invalid types to improve the accuracy of the spine detection. We evaluate the proposed approach by comparing with the manual results in terms of backbone length, spine number, spine length, and spine density.

  11. Pathological Consequence of Misguided Dendritic Cell Differentiation in Histiocytic Diseases

    OpenAIRE

    Berres, Marie-Luise; Allen, Carl E.; Merad, Miriam

    2013-01-01

    Histiocytic disorders represent a group of complex pathologies characterized by the accumulation of histiocytes, an old term for tissue-resident macrophages and dendritic cells. Langerhans cell histiocytosis is the most frequent of histiocytosis in humans and has been thought to arise from the abnormal accumulation of epidermal dendritic cells called Langerhans cells. In this chapter, we discuss the origin and differentiation of Langerhans cells and dendritic cells and present accumulated evi...

  12. Murid herpesvirus-4 exploits dendritic cells to infect B cells

    OpenAIRE

    Miguel Gaspar; May, Janet S.; Soumi Sukla; Bruno Frederico; Michael B Gill; Smith, Christopher M.; Belz, Gabrielle T.; Stevenson, Philip G.

    2011-01-01

    Author Summary We detect invading viruses with dendritic cells and eliminate them with lymphocytes. A key interaction is lymphocyte activation by dendritic cells presenting viral antigens. Not all viruses can be eliminated, and some that persist deliberately colonize lymphocytes and dendritic cells, such that parasitism and host defence co-exist within the same sites. Once established, these infections are very hard to eliminate. Therefore to vaccinate against them we must determine how infec...

  13. Nanoparticle-aggregated 3D monocrystalline gold dendritic nanostructures

    International Nuclear Information System (INIS)

    In this paper, through a simple and fast electroless metal deposition route, gold dendritic nanostructures are synthesized in aqueous conditions. The gold dendrites with a threefold symmetric characteristic were built up of numerous nanoparticles roughly 5-10 nm in size. The aggregated nanoparticles spontaneously experience a self-assembly process along crystallographic orientations and finally form a monocrystalline dendrite. An oriented attachment mechanism can be used to explain the nanoparticle-aggregated self-assembly process

  14. CTAB-Influenced Electrochemical Dissolution of Silver Dendrites.

    Science.gov (United States)

    O'Regan, Colm; Zhu, Xi; Zhong, Jun; Anand, Utkarsh; Lu, Jingyu; Su, Haibin; Mirsaidov, Utkur

    2016-04-19

    Dendrite formation on the electrodes of a rechargeable battery during the charge-discharge cycle limits its capacity and application due to short-circuits and potential ignition. However, understanding of the underlying dendrite growth and dissolution mechanisms is limited. Here, the electrochemical growth and dissolution of silver dendrites on platinum electrodes immersed in an aqueous silver nitrate (AgNO3) electrolyte solution was investigated using in situ liquid-cell transmission electron microscopy (TEM). The dissolution of Ag dendrites in an AgNO3 solution with added cetyltrimethylammonium bromide (CTAB) surfactant was compared to the dissolution of Ag dendrites in a pure aqueous AgNO3 solution. Significantly, when CTAB was added, dendrite dissolution proceeded in a step-by-step manner, resulting in nanoparticle formation and transient microgrowth stages due to Ostwald ripening. This resulted in complete dissolution of dendrites and "cleaning" of the cell of any silver metal. This is critical for practical battery applications because "dead" lithium is known to cause short circuits and high-discharge rates. In contrast to this, in a pure aqueous AgNO3 solution, without surfactant, dendrites dissolved incompletely back into solution, leaving behind minute traces of disconnected silver particles. Finally, a mechanism for the CTAB-influenced dissolution of silver dendrites was proposed based on electrical field dependent binding energy of CTA(+) to silver. PMID:27017834

  15. Mapping homeostatic synaptic plasticity using cable properties of dendrites.

    Science.gov (United States)

    Queenan, B N; Lee, K J; Tan, H; Huganir, R L; Vicini, S; Pak, D T S

    2016-02-19

    When chronically silenced, cortical and hippocampal neurons homeostatically upregulate excitatory synaptic function. However, the subcellular position of such changes on the dendritic tree is not clear. We exploited the cable-filtering properties of dendrites to derive a parameter, the dendritic filtering index (DFI), to map the spatial distribution of synaptic currents. Our analysis indicates that young rat cortical neurons globally scale AMPA receptor-mediated currents, while mature hippocampal neurons do not, revealing distinct homeostatic strategies between brain regions and developmental stages. The DFI presents a useful tool for mapping the dendritic origin of synaptic currents and the location of synaptic plasticity changes.

  16. Semi-solid Forming of a Damper Housing with Dendritic and Non-dendritic Al-Si-Mg Alloy

    Institute of Scientific and Technical Information of China (English)

    ChenCM; YangCC; ChaoCG

    2001-01-01

    A motorcycle component of damper housing was made by semi-solid forming process. This was used to investigate the effect of microstructures of feedstock on the formability of semisolid process. The soundness and microstructures of casting parts made by dendritic and non-dendritic feedstock were investigated. Separating of liquid phase was found in the casting produced by dendritic feedstock, which might result in defects of porosity, while uniform microstructures were found in the casting produced by no...

  17. Disruptive event analysis: volcanism and igneous intrusion

    International Nuclear Information System (INIS)

    Three basic topics are addressed for the disruptive event analysis: first, the range of disruptive consequences of a radioactive waste repository by volcanic activity; second, the possible reduction of the risk of disruption by volcanic activity through selective siting of a repository; and third, the quantification of the probability of repository disruption by volcanic activity

  18. Ternary eutectic dendrites: Pattern formation and scaling properties

    International Nuclear Information System (INIS)

    Extending previous work [Pusztai et al., Phys. Rev. E 87, 032401 (2013)], we have studied the formation of eutectic dendrites in a model ternary system within the framework of the phase-field theory. We have mapped out the domain in which two-phase dendritic structures grow. With increasing pulling velocity, the following sequence of growth morphologies is observed: flat front lamellae → eutectic colonies → eutectic dendritesdendrites with target pattern → partitionless dendrites → partitionless flat front. We confirm that the two-phase and one-phase dendrites have similar forms and display a similar scaling of the dendrite tip radius with the interface free energy. It is also found that the possible eutectic patterns include the target pattern, and single- and multiarm spirals, of which the thermal fluctuations choose. The most probable number of spiral arms increases with increasing tip radius and with decreasing kinetic anisotropy. Our numerical simulations confirm that in agreement with the assumptions of a recent analysis of two-phase dendrites [Akamatsu et al., Phys. Rev. Lett. 112, 105502 (2014)], the Jackson-Hunt scaling of the eutectic wavelength with pulling velocity is obeyed in the parameter domain explored, and that the natural eutectic wavelength is proportional to the tip radius of the two-phase dendrites. Finally, we find that it is very difficult/virtually impossible to form spiraling two-phase dendrites without anisotropy, an observation that seems to contradict the expectations of Akamatsu et al. Yet, it cannot be excluded that in isotropic systems, two-phase dendrites are rare events difficult to observe in simulations

  19. Ternary eutectic dendrites: Pattern formation and scaling properties

    Energy Technology Data Exchange (ETDEWEB)

    Rátkai, László; Szállás, Attila; Pusztai, Tamás [Institute for Solid State Physics and Optics, Wigner Research Centre for Physics, P.O. Box 49, H-1525 Budapest (Hungary); Mohri, Tetsuo [Center for Computational Materials Science, Institute for Materials Research, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577 (Japan); Gránásy, László, E-mail: granasy.laszlo@wigner.mta.hu [Institute for Solid State Physics and Optics, Wigner Research Centre for Physics, P.O. Box 49, H-1525 Budapest (Hungary); Brunel University, Uxbridge, Middlesex UB8 3PH (United Kingdom)

    2015-04-21

    Extending previous work [Pusztai et al., Phys. Rev. E 87, 032401 (2013)], we have studied the formation of eutectic dendrites in a model ternary system within the framework of the phase-field theory. We have mapped out the domain in which two-phase dendritic structures grow. With increasing pulling velocity, the following sequence of growth morphologies is observed: flat front lamellae → eutectic colonies → eutectic dendritesdendrites with target pattern → partitionless dendrites → partitionless flat front. We confirm that the two-phase and one-phase dendrites have similar forms and display a similar scaling of the dendrite tip radius with the interface free energy. It is also found that the possible eutectic patterns include the target pattern, and single- and multiarm spirals, of which the thermal fluctuations choose. The most probable number of spiral arms increases with increasing tip radius and with decreasing kinetic anisotropy. Our numerical simulations confirm that in agreement with the assumptions of a recent analysis of two-phase dendrites [Akamatsu et al., Phys. Rev. Lett. 112, 105502 (2014)], the Jackson-Hunt scaling of the eutectic wavelength with pulling velocity is obeyed in the parameter domain explored, and that the natural eutectic wavelength is proportional to the tip radius of the two-phase dendrites. Finally, we find that it is very difficult/virtually impossible to form spiraling two-phase dendrites without anisotropy, an observation that seems to contradict the expectations of Akamatsu et al. Yet, it cannot be excluded that in isotropic systems, two-phase dendrites are rare events difficult to observe in simulations.

  20. TAD disruption as oncogenic driver.

    Science.gov (United States)

    Valton, Anne-Laure; Dekker, Job

    2016-02-01

    Topologically Associating Domains (TADs) are conserved during evolution and play roles in guiding and constraining long-range regulation of gene expression. Disruption of TAD boundaries results in aberrant gene expression by exposing genes to inappropriate regulatory elements. Recent studies have shown that TAD disruption is often found in cancer cells and contributes to oncogenesis through two mechanisms. One mechanism locally disrupts domains by deleting or mutating a TAD boundary leading to fusion of the two adjacent TADs. The other mechanism involves genomic rearrangements that break up TADs and creates new ones without directly affecting TAD boundaries. Understanding the mechanisms by which TADs form and control long-range chromatin interactions will therefore not only provide insights into the mechanism of gene regulation in general, but will also reveal how genomic rearrangements and mutations in cancer genomes can lead to misregulation of oncogenes and tumor suppressors. PMID:27111891

  1. Buoyancy effects of a growing, isolated dendrite

    Science.gov (United States)

    Canright, D.; Davis, S. H.

    1991-01-01

    The buoyancy effect of a growing isolated dendrite on the solidification process in the undercooling liquid material was investigated by developing an analytic solution to the growth/convection problem in powers of a buoyancy parameter G. The solution depends on the Prandtl number P and the Stefan number S (undercooling) for the local velocity and thermal fields and also the buoyant alteration of the interface shape. Results suggest that buoyancy effect for metals (low P) may be qualitatively different from that for organics (high P).

  2. Plasticity of dendritic spines: subcompartmentalization of signaling.

    Science.gov (United States)

    Colgan, Lesley A; Yasuda, Ryohei

    2014-01-01

    The ability to induce and study neuronal plasticity in single dendritic spines has greatly advanced our understanding of the signaling mechanisms that mediate long-term potentiation. It is now clear that in addition to compartmentalization by the individual spine, subcompartmentalization of biochemical signals occurs at specialized microdomains within the spine. The spatiotemporal coordination of these complex cascades allows for the concomitant remodeling of the postsynaptic density and actin spinoskeleton and for the regulation of membrane traffic to express functional and structural plasticity. Here, we highlight recent findings in the signaling cascades at spine microdomains as well as the challenges and approaches to studying plasticity at the spine level. PMID:24215443

  3. Social play in juvenile hamsters alters dendritic morphology in the medial prefrontal cortex and attenuates effects of social stress in adulthood.

    Science.gov (United States)

    Burleson, Cody A; Pedersen, Robert W; Seddighi, Sahba; DeBusk, Lauren E; Burghardt, Gordon M; Cooper, Matthew A

    2016-08-01

    Social play is a fundamental aspect of behavioral development in many species. Social play deprivation in rats alters dendritic morphology in the ventromedial prefrontal cortex (vmPFC) and we have shown that this brain region regulates responses to social defeat stress in Syrian hamsters. In this study, we tested whether play deprivation during the juvenile period disrupts dendritic morphology in the prefrontal cortex and potentiates the effects of social defeat stress. At weaning, male hamsters were either group-housed with peers or pair-housed with their mother, with whom they do not play. In adulthood, animals received acute social defeat stress or no-defeat control treatment. The hamsters were then tested for a conditioned defeat response in a social interaction test with a novel intruder, and were also tested for social avoidance of a familiar opponent. Brains were collected for Golgi-Cox staining and analysis of dendritic morphology in the infralimbic (IL), prelimbic (PL), and orbitofrontal cortex (OFC). Play-deprived animals showed an increased conditioned defeat response and elevated avoidance of a familiar opponent compared with play-exposed animals. Furthermore, play-deprived animals showed increased total length and branch points in apical dendrites of pyramidal neurons in the IL and PL cortices, but not in the OFC. These findings suggest that social play deprivation in juvenile hamsters disrupts neuronal development in the vmPFC and increases vulnerability to the effects of social stress in adulthood. Overall, these results suggest that social play is necessary for the natural dendritic pruning process during adolescence and promotes coping with stress in adulthood. (PsycINFO Database Record PMID:27176563

  4. Social play in juvenile hamsters alters dendritic morphology in the medial prefrontal cortex and attenuates effects of social stress in adulthood.

    Science.gov (United States)

    Burleson, Cody A; Pedersen, Robert W; Seddighi, Sahba; DeBusk, Lauren E; Burghardt, Gordon M; Cooper, Matthew A

    2016-08-01

    Social play is a fundamental aspect of behavioral development in many species. Social play deprivation in rats alters dendritic morphology in the ventromedial prefrontal cortex (vmPFC) and we have shown that this brain region regulates responses to social defeat stress in Syrian hamsters. In this study, we tested whether play deprivation during the juvenile period disrupts dendritic morphology in the prefrontal cortex and potentiates the effects of social defeat stress. At weaning, male hamsters were either group-housed with peers or pair-housed with their mother, with whom they do not play. In adulthood, animals received acute social defeat stress or no-defeat control treatment. The hamsters were then tested for a conditioned defeat response in a social interaction test with a novel intruder, and were also tested for social avoidance of a familiar opponent. Brains were collected for Golgi-Cox staining and analysis of dendritic morphology in the infralimbic (IL), prelimbic (PL), and orbitofrontal cortex (OFC). Play-deprived animals showed an increased conditioned defeat response and elevated avoidance of a familiar opponent compared with play-exposed animals. Furthermore, play-deprived animals showed increased total length and branch points in apical dendrites of pyramidal neurons in the IL and PL cortices, but not in the OFC. These findings suggest that social play deprivation in juvenile hamsters disrupts neuronal development in the vmPFC and increases vulnerability to the effects of social stress in adulthood. Overall, these results suggest that social play is necessary for the natural dendritic pruning process during adolescence and promotes coping with stress in adulthood. (PsycINFO Database Record

  5. Contribution of sublinear and supralinear dendritic integration to neuronal computations

    Directory of Open Access Journals (Sweden)

    Alexandra eTran-Van-Minh

    2015-03-01

    Full Text Available Nonlinear dendritic integration is thought to increase the computational ability of neurons. Most studies focus on how supralinear summation of excitatory synaptic responses arising from clustered inputs within single dendrites result in the enhancement of neuronal firing, enabling simple computations such as feature detection. Recent reports have shown that sublinear summation is also a prominent dendritic operation, extending the range of subthreshold input-output transformations conferred by dendrites. Like supralinear operations, sublinear dendritic operations also increase the repertoire of neuronal computations, but feature extraction requires different synaptic connectivity strategies for each of these operations. In this article we will review the experimental and theoretical findings describing the biophysical determinants of the three primary classes of dendritic operations: linear, sublinear, and supralinear. We then review a Boolean algebra-based analysis of simplified neuron models, which provides insight into how dendritic operations influence neuronal computations. We highlight how neuronal computations are critically dependent on the interplay of dendritic properties (morphology and voltage-gated channel expression, spiking threshold and distribution of synaptic inputs carrying particular sensory features. Finally, we describe how global (scattered and local (clustered integration strategies permit the implementation of similar classes of computations, one example being the object feature binding problem.

  6. Contribution of sublinear and supralinear dendritic integration to neuronal computations.

    Science.gov (United States)

    Tran-Van-Minh, Alexandra; Cazé, Romain D; Abrahamsson, Therése; Cathala, Laurence; Gutkin, Boris S; DiGregorio, David A

    2015-01-01

    Nonlinear dendritic integration is thought to increase the computational ability of neurons. Most studies focus on how supralinear summation of excitatory synaptic responses arising from clustered inputs within single dendrites result in the enhancement of neuronal firing, enabling simple computations such as feature detection. Recent reports have shown that sublinear summation is also a prominent dendritic operation, extending the range of subthreshold input-output (sI/O) transformations conferred by dendrites. Like supralinear operations, sublinear dendritic operations also increase the repertoire of neuronal computations, but feature extraction requires different synaptic connectivity strategies for each of these operations. In this article we will review the experimental and theoretical findings describing the biophysical determinants of the three primary classes of dendritic operations: linear, sublinear, and supralinear. We then review a Boolean algebra-based analysis of simplified neuron models, which provides insight into how dendritic operations influence neuronal computations. We highlight how neuronal computations are critically dependent on the interplay of dendritic properties (morphology and voltage-gated channel expression), spiking threshold and distribution of synaptic inputs carrying particular sensory features. Finally, we describe how global (scattered) and local (clustered) integration strategies permit the implementation of similar classes of computations, one example being the object feature binding problem.

  7. Dendritic Spines in Depression: What We Learned from Animal Models

    OpenAIRE

    Hui Qiao; Ming-Xing Li; Chang Xu; Hui-Bin Chen; Shu-Cheng An; Xin-Ming Ma

    2016-01-01

    Depression, a severe psychiatric disorder, has been studied for decades, but the underlying mechanisms still remain largely unknown. Depression is closely associated with alterations in dendritic spine morphology and spine density. Therefore, understanding dendritic spines is vital for uncovering the mechanisms underlying depression. Several chronic stress models, including chronic restraint stress (CRS), chronic unpredictable mild stress (CUMS), and chronic social defeat stress (CSDS), have ...

  8. Extracellular matrix control of dendritic spine and synapse structure and plasticity in adulthood

    Directory of Open Access Journals (Sweden)

    Aaron D Levy

    2014-10-01

    Full Text Available Dendritic spines are the receptive contacts at most excitatory synapses in the central nervous system. Spines are dynamic in the developing brain, changing shape as they mature as well as appearing and disappearing as they make and break connections. Spines become much more stable in adulthood, and spine structure must be actively maintained to support established circuit function. At the same time, adult spines must retain some plasticity so their structure can be modified by activity and experience. As such, the regulation of spine stability and remodeling in the adult animal is critical for normal function, and disruption of these processes is associated with a variety of late onset diseases including schizophrenia and Alzheimer’s disease. The extracellular matrix (ECM, composed of a meshwork of proteins and proteoglycans, is a critical regulator of spine and synapse stability and plasticity. While the role of ECM receptors in spine regulation has been extensively studied, considerably less research has focused directly on the role of specific ECM ligands. Here, we review the evidence for a role of several brain ECM ligands and remodeling proteases in the regulation of dendritic spine and synapse formation, plasticity, and stability in adults.

  9. Modeling of dendritic growth in the presence of convection

    Institute of Scientific and Technical Information of China (English)

    ZHU; Mingfang; DAI; Ting; LEE; Sungyoon; HONG; Chunpyo

    2005-01-01

    A two-dimensional coupling modified cellular automaton (MCA)-transport model has been employed to investigate the asymmetrical dendritic growth behavior in a flowing melt. In the present model, the cellular automaton method for crystal growth is incorporated with a transport model, for numerical calculating of the fluid flow and mass transport by both convection and diffusion. The MCA takes into account the effects of the thermal, the constitutional and the curvature undercoolings on dendritic growth. It also considers the preferred growth orientation of crystal and solute redistribution during solidification. In the transport model, the SIMPLE scheme and a fully implicit finite volume method are employed to solve the governing equations of momentum and species transfers. The present model was applied to simulating the evolution of a single dendrite and multi-dendrites of an Al-3mass%Cu alloy in a forced flow. The simulated results show that dendritic growth morphology is strongly influenced by melt convection.

  10. Immune Monitoring Using mRNA-Transfected Dendritic Cells.

    Science.gov (United States)

    Borch, Troels Holz; Svane, Inge Marie; Met, Özcan

    2016-01-01

    Dendritic cells are known to be the most potent antigen presenting cell in the immune system and are used as cellular adjuvants in therapeutic anticancer vaccines using various tumor-associated antigens or their derivatives. One way of loading antigen into the dendritic cells is by mRNA electroporation, ensuring presentation of antigen through major histocompatibility complex I and potentially activating T cells, enabling them to kill the tumor cells. Despite extensive research in the field, only one dendritic cell-based vaccine has been approved. There is therefore a great need to elucidate and understand the immunological impact of dendritic cell vaccination in order to improve clinical benefit. In this chapter, we describe a method for performing immune monitoring using peripheral blood mononuclear cells and autologous dendritic cells transfected with tumor-associated antigen-encoding mRNA. PMID:27236804

  11. Synthesis and field emission properties of Cu dendritic nanostructures

    Science.gov (United States)

    Xu, Jianwen; Yu, Ke; Zhu, Ziqiang

    2010-03-01

    Cu dendritic nanostructures were synthesized on ITO glass substructure by electrochemical deposition. SEM images showed that these Cu dendritic nanostuctures revealed a clear and well-defined dendritic fractal structure with a pronounced trunk and highly ordered branches distributed on both sides of the trunk. The diffusion-limited aggregation (DLA) model was used to explain the fractal growth of Cu dendritic nanostructures. Field emission properties of these Cu dendritic nanostructures were measured, which have possessed good performance with the turn-on field of 7.5 V/μm (defined as the electric field required to be detected at a current density of 0.1 mA/cm 2) and the field enhancement factor β of 1094.

  12. JNK1 Controls Dendritic Field Size in L2/3 and L5 of the Motor Cortex, Constrains Soma Size and Influences Fine Motor Coordination

    Directory of Open Access Journals (Sweden)

    Emilia eKomulainen

    2014-09-01

    Full Text Available Genetic anomalies on the JNK pathway confer susceptibility to autism spectrum disorders, schizophrenia and intellectual disability. The mechanism whereby a gain or loss of function in JNK signaling predisposes to these prevalent dendrite disorders, with associated motor dysfunction, remains unclear. Here we find that JNK1 regulates the dendritic field of L2/3 and L5 pyramidal neurons of the mouse motor cortex (M1, the main excitatory pathway controlling voluntary movement. In Jnk1-/- mice, basal dendrite branching of L5 pyramidal neurons is increased in M1, as is cell soma size, whereas in L2/3, dendritic arborization is decreased. We show that JNK1 phosphorylates rat HMW-MAP2 on T1619, T1622 and T1625 (Uniprot P15146 corresponding to mouse T1617, T1620, T1623, to create a binding motif, that is critical for MAP2 interaction with and stabilization of microtubules, and dendrite growth control. Targeted expression in M1 of GFP-HMW-MAP2 that is pseudo-phosphorylated on T1619, T1622 and T1625 increases dendrite complexity in L2/3 indicating that JNK1 phosphorylation of HMW-MAP2 regulates the dendritic field. Consistent with the morphological changes observed in L2/3 and L5, Jnk1-/- mice exhibit deficits in limb placement and motor coordination, while stride length is reduced in older animals. In summary, JNK1 phosphorylates HMW-MAP2 to increase its stabilization of microtubules while at the same time controlling dendritic fields in the main excitatory pathway of M1. Moreover, JNK1 contributes to normal functioning of fine motor coordination. We report for the first time, a quantitative sholl analysis of dendrite architecture, and of motor behavior in Jnk1-/- mice. Our results illustrate the molecular and behavioral consequences of interrupted JNK1 signaling and provide new ground for mechanistic understanding of those prevalent neuropyschiatric disorders where genetic disruption of the JNK pathway is central.

  13. Disruptive Innovation in Healthcare & Rehabilitation

    DEFF Research Database (Denmark)

    Brooks, Anthony Lewis

    2014-01-01

    will pay. Disruptive Innovation in context of the author’s body of work in healthcare and rehabilitation relates to how development of a cloud-based converged infrastructure resource, similar to that conceived in a national (Danish) study titled Humanics, can act as an accessible data and knowledge...

  14. Dendritic Cells in vivo and in vitro

    Institute of Scientific and Technical Information of China (English)

    Hui Wan; Marcel Dupasquier

    2005-01-01

    Dendritic cells (DC) are crucial cells of the immune system, and bridged the essential connection between innate and adaptive immunity. They reside in the periphery as sentinels where they take up antigens. Upon activation,they migrate to lymphoid organs and present there the processed antigens to T cells, thereby activating them and eliciting a potent immune response. Dendritic cells are bone marrow-derived cells, still big controversies exist about their in vivo development. In vitro, DC can be generated from multiple precursor cells, among them lymphoid and myeloid committed progenitors. Although it remains unknown how DC are generated in vivo,studying the functions of in vitro generated DC results in fundamental knowledge of the DC biology with promising applications for future medicine. Therefore, in this review, we present current protocols for the generation of DC from precursors in vitro. We will do this for the mouse system, where most research occurs and for the human system, where research concentrates on implementing DC biology in disease treatments.

  15. Dendritic Cells in vivo and in vitro

    Institute of Scientific and Technical Information of China (English)

    HuiWan; MarcelDupasquier

    2005-01-01

    Dendritic cells (DC) are crucial cells of the immune system, and bridged the essential connection between innate and adaptive immunity. They reside in the periphery as sentinels where they take up antigens. Upon activation, they migrate to lymphoid organs and present there the processed antigens to T cells, thereby activating them and eliciting a potent immune response. Dendritic cells are bone marrow-derived cells, still big controversies exist about their in vivo development. In vitro, DC can be generated from multiple precursor cells, among them lymphoid and myeloid committed progenitors. Although it remains unknown how DC are generated in vivo, studying the functions of in vitro generated DC results in fundamental knowledge of the DC biology with promising applications for future medicine. Therefore, in this review, we present current protocols for the generation of DC from precursors in vitro. We will do this for the mouse system, where most research occurs and for the human system, where research concentrates on implementing DC biology in disease treatments. Cellular & Molecular Immunology. 2005;2(1):28-35.

  16. Adolescent cocaine exposure simplifies orbitofrontal cortical dendritic arbors

    Directory of Open Access Journals (Sweden)

    Lauren M DePoy

    2014-10-01

    Full Text Available Cocaine and amphetamine remodel dendritic spines within discrete cortico-limbic brain structures including the orbitofrontal cortex (oPFC. Whether dendrite structure is similarly affected, and whether pre-existing cellular characteristics influence behavioral vulnerabilities to drugs of abuse, remain unclear. Animal models provide an ideal venue to address these issues because neurobehavioral phenotypes can be defined both before, and following, drug exposure. We exposed mice to cocaine from postnatal days 31-35, corresponding to early adolescence, using a dosing protocol that causes impairments in an instrumental reversal task in adulthood. We then imaged and reconstructed excitatory neurons in deep-layer oPFC. Prior cocaine exposure shortened and simplified arbors, particularly in the basal region. Next, we imaged and reconstructed orbital neurons in a developmental-genetic model of cocaine vulnerability – the p190rhogap+/- mouse. p190RhoGAP is an actin cytoskeleton regulatory protein that stabilizes dendrites and dendritic spines, and p190rhogap+/- mice develop rapid and robust locomotor activation in response to cocaine. Despite this, oPFC dendritic arbors were intact in drug-naïve p190rhogap+/- mice. Together, these findings provide evidence that adolescent cocaine exposure has long-term effects on dendrite structure in the oPFC, and they suggest that cocaine-induced modifications in dendrite structure may contribute to the behavioral effects of cocaine more so than pre-existing structural abnormalities in this cell population.

  17. Dendritic mitochondria reach stable positions during circuit development

    Science.gov (United States)

    Faits, Michelle C; Zhang, Chunmeng; Soto, Florentina; Kerschensteiner, Daniel

    2016-01-01

    Mitochondria move throughout neuronal dendrites and localize to sites of energy demand. The prevailing view of dendritic mitochondria as highly motile organelles whose distribution is continually adjusted by neuronal activity via Ca2+-dependent arrests is based on observations in cultured neurons exposed to artificial stimuli. Here, we analyze the movements of mitochondria in ganglion cell dendrites in the intact retina. We find that whereas during development 30% of mitochondria are motile at any time, as dendrites mature, mitochondria all but stop moving and localize stably to synapses and branch points. Neither spontaneous nor sensory-evoked activity and Ca2+ transients alter motility of dendritic mitochondria; and pathological hyperactivity in a mouse model of retinal degeneration elevates rather than reduces motility. Thus, our findings indicate that dendritic mitochondria reach stable positions during a critical developmental period of high motility, and challenge current views about the role of activity in regulating mitochondrial transport in dendrites. DOI: http://dx.doi.org/10.7554/eLife.11583.001 PMID:26742087

  18. Control of dendritic morphogenesis by Trio in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Madhuri Shivalkar

    Full Text Available Abl tyrosine kinase and its effectors among the Rho family of GTPases each act to control dendritic morphogenesis in Drosophila. It has not been established, however, which of the many GTPase regulators in the cell link these signaling molecules in the dendrite. In axons, the bifunctional guanine exchange factor, Trio, is an essential link between the Abl tyrosine kinase signaling pathway and Rho GTPases, particularly Rac, allowing these systems to act coordinately to control actin organization. In dendritic morphogenesis, however, Abl and Rac have contrary rather than reinforcing effects, raising the question of whether Trio is involved, and if so, whether it acts through Rac, Rho or both. We now find that Trio is expressed in sensory neurons of the Drosophila embryo and regulates their dendritic arborization. trio mutants display a reduction in dendritic branching and increase in average branch length, whereas over-expression of trio has the opposite effect. We further show that it is the Rac GEF domain of Trio, and not its Rho GEF domain that is primarily responsible for the dendritic function of Trio. Thus, Trio shapes the complexity of dendritic arbors and does so in a way that mimics the effects of its target, Rac.

  19. Design of tumor-specific immunotherapies using dendritic cells - effect of bromelain on dendritic cell maturation

    OpenAIRE

    Karlsen, Marie

    2009-01-01

    Immunotherapy using dendritic cells (DC) has shown promising results in clinical trials, but few relevant successes are recorded. Therefore, the choice of an appropriate DC population is critical for the outcome of this treatment. The DC used today in immunotherapy are often matured with a cytokine cocktail consisting of TNF-α, IL-1β, IL-6 and PGE2. These cells have deficits in their cytokine production, and also their migratory capacity in vivo needs improvement. After being introduced to br...

  20. Specific disruption of hippocampal mossy fiber synapses in a mouse model of familial Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Scott A Wilke

    Full Text Available The earliest stages of Alzheimer's disease (AD are characterized by deficits in memory and cognition indicating hippocampal pathology. While it is now recognized that synapse dysfunction precedes the hallmark pathological findings of AD, it is unclear if specific hippocampal synapses are particularly vulnerable. Since the mossy fiber (MF synapse between dentate gyrus (DG and CA3 regions underlies critical functions disrupted in AD, we utilized serial block-face electron microscopy (SBEM to analyze MF microcircuitry in a mouse model of familial Alzheimer's disease (FAD. FAD mutant MF terminal complexes were severely disrupted compared to control - they were smaller, contacted fewer postsynaptic spines and had greater numbers of presynaptic filopodial processes. Multi-headed CA3 dendritic spines in the FAD mutant condition were reduced in complexity and had significantly smaller sites of synaptic contact. Significantly, there was no change in the volume of classical dendritic spines at neighboring inputs to CA3 neurons suggesting input-specific defects in the early course of AD related pathology. These data indicate a specific vulnerability of the DG-CA3 network in AD pathogenesis and demonstrate the utility of SBEM to assess circuit specific alterations in mouse models of human disease.

  1. Disrupting the habit of interviewing

    Directory of Open Access Journals (Sweden)

    Eileen Honan

    2014-06-01

    Full Text Available This paper contributes to the growing domain of ‘post-qualitative’ research and experiments with a new (representational form to move away from traditional and clichéd descriptions of research methods. In this paper, I want to interrogate the category of interview, and the habit of interviewing, to disrupt the clichés, so as to allow thinking of different ways of writing/speaking/representing the interactions between researcher and researched that will breathe new life into qualitative inquiries. I will attempt to flatten and shred, destabilise and disrupt our common-sense ideas about interview, including those held most sacred to the qualitative community, that of anonymity and confidentiality, as well as the privilege of the ‘transcript’ in re-presenting interview data.

  2. Optimal Disruption of Complex Networks

    CERN Document Server

    Zhao, Jin-Hua

    2016-01-01

    The collection of all the strongly connected components in a directed graph, among each cluster of which any node has a path to another node, is a typical example of the intertwining structure and dynamics in complex networks, as its relative size indicates network cohesion and it also composes of all the feedback cycles in the network. Here we consider finding an optimal strategy with minimal effort in removal arcs (for example, deactivation of directed interactions) to fragment all the strongly connected components into tree structure with no effect from feedback mechanism. We map the optimal network disruption problem to the minimal feedback arc set problem, a non-deterministically polynomial hard combinatorial optimization problem in graph theory. We solve the problem with statistical physical methods from spin glass theory, resulting in a simple numerical method to extract sub-optimal disruption arc sets with significantly better results than a local heuristic method and a simulated annealing method both...

  3. Fractal structures of dendrites in GaSe crystals

    Science.gov (United States)

    Kolesnikov, N. N.; Borisenko, E. B.; Borisenko, D. N.; Bozhko, S. I.

    2008-07-01

    Solidification of melts at substantial supercooling is associated with instability on the growth front. This causes growth of dendrites, which form as a branched tree in a crystal. In the layered melt-grown GaSe crystals dendrites are observed, if growth rates are rather high [N.N. Kolesnikov, E.B. Borisenko, D.N. Borisenko, V.K. Gartman, Influence of growth conditions on microstructure and properties of GaSe crystals, J. Crystal Growth 300 (2) (2007) 294-298]. Models based on solution of the thermal diffusion problem are traditionally used to describe dendrite growth. Solution of this problem requires information about several physical parameters, such as diffusion coefficient, heat conductivity coefficient and supercooling at the solid/liquid interface. The study of scale invariance of dendrites formed in a crystal provides a new approach to solution of the dynamic growth problem. The calculated fractal dimensionality of the experimentally observed dendrites in GaSe crystals is D=1.7. It coincides with dimensionality of the clusters obtained through computer simulation in terms of the model of diffusion-limited aggregation (DLA). This result provides a new approach to description of the dynamics of dendrite growth. We have shown that the dendrite growth mechanism in the layered semiconductor crystals can be described by a two-dimensional DLA model. It is shown that probabilistic simulation can be used to show the development of a dendrite in any material. In contrast to the classical theories of dendrite growth, this approach does not require information on physical parameters.

  4. Disruptive technologies in higher education

    Directory of Open Access Journals (Sweden)

    Michael Flavin

    2012-08-01

    Full Text Available This paper analyses the role of “disruptive” innovative technologies in higher education. In this country and elsewhere, Higher Education Institutions (HEIs have invested significant sums in learning technologies, with Virtual Learning Environments (VLEs being more or less universal, but these technologies have not been universally adopted and used by students and staff. Instead, other technologies not owned or controlled by HEIs are widely used to support learning and teaching. According to Christensen's theory of Disruptive Innovation, these disruptive technologies are not designed explicitly to support learning and teaching in higher education, but have educational potential. This study uses Activity Theory and Expansive Learning to analyse data regarding the impact of disruptive technologies. The data were obtained through a questionnaire survey about awareness and use of technologies, and through observation and interviews, exploring participants’ actual practice. The survey answers tended to endorse Disruptive Innovation theory, with participants establishing meanings for technologies through their use of them, rather than in keeping with a designer's intentions. Observation revealed that learners use a narrow range of technologies to support learning, but with a tendency to use resources other than those supplied by their HEIs. Interviews showed that participants use simple and convenient technologies to support their learning and teaching. This study identifies a contradiction between learning technologies made available by HEIs, and technologies used in practice. There is no evidence to suggest that a wide range of technologies is being used to support learning and teaching. Instead, a small range of technologies is being used for a wide range of tasks. Students and lecturers are not dependent on their HEIs to support learning and teaching. Instead, they self-select technologies, with use weighted towards established brands. The

  5. Immunotherapy of hematological malignancies using dendritic cells.

    Science.gov (United States)

    Van de Velde, Ann L R; Berneman, Zwi N; Van Tendeloo, Viggo F I

    2008-03-01

    The arsenal of therapeutic weapons against hematological malignancies is constantly growing. Unravelling the secrets of tumor immunobiology has allowed researchers to manipulate the immune system in order to stimulate tumor immunity or to bypass tumor-induced immunosuppression. An area of great interest is active specific immunotherapy where dendritic cell (DC)-based therapeutic vaccines for cancer have definitely grabbed the spotlight. DC are intensively investigated as cellular adjuvants to harness the immune system to fight off cancer by augmenting the number and effector functions of tumor-specific CD8+ cytotoxic T lymphocytes. In the present review we present a comprehensive synopsis and an update of the use of DC in hematological malignancies. In the future, more basic research as well as more clinical trials are warranted to fully establish the value of DC vaccination as an adjuvant therapy for modern hematological oncology. PMID:18390412

  6. Plasmacytoid Dendritic Cells: From Heart to Vessels

    Directory of Open Access Journals (Sweden)

    Rosalinda Sorrentino

    2010-01-01

    Full Text Available Cardiovascular diseases, formerly only attributed to the alterations of the stromal component, are now recognized as immune-based pathologies. Plasmacytoid Dendritic Cells (pDCs are important immune orchestrators in heart and vessels. They highly produce IFN type I that promote the polarization of T cells towards a Th1 phenotype; however, pDCs can also participate to suppressive networks via the recruitment of T regulatory cells that downmodulate proinflammatory responses. pDCs populate the vessel wall layers during pathological conditions, such as atherosclerosis. It is thus clear that a better identification of pDCs activity in cardiovascular diseases can not only elucidate pathological mechanisms but also lead to new therapeutic approaches.

  7. Isolation of Human Skin Dendritic Cell Subsets.

    Science.gov (United States)

    Gunawan, Merry; Jardine, Laura; Haniffa, Muzlifah

    2016-01-01

    Dendritic cells (DCs) are specialized leukocytes with antigen-processing and antigen-presenting functions. DCs can be divided into distinct subsets by anatomical location, phenotype and function. In human, the two most accessible tissues to study leukocytes are peripheral blood and skin. DCs are rare in human peripheral blood (Nestle et al., J Immunol 151:6535-6545, 1993). These factors led to the extensive use of skin DCs as the "prototype" migratory DCs in human studies. In this chapter, we detail the protocols to isolate DCs and resident macrophages from human skin. We also provide a multiparameter flow cytometry gating strategy to identify human skin DCs and to distinguish them from macrophages. PMID:27142012

  8. HOW TO IDENTIFY DISRUPTIVE NEW BUSINESSES

    OpenAIRE

    Elizabeth Robles

    2015-01-01

    In almost any industry, the most dramatic stories of growth and success were launched from a platform of disruptive innovation (Christensen et al., 2002). The probability of creating a successful, new growth business is 10 times greater if the innovators pursue a disruptive strategy rather than a sustaining one. Genuinely disruptive innovations are the ones that result in the creation of entirely new markets and business models. Few companies have introduced these innovations. Disruptive inno...

  9. Thyroid effects of endocrine disrupting chemicals

    DEFF Research Database (Denmark)

    Boas, Malene; Feldt-Rasmussen, Ulla; Main, Katharina M

    2012-01-01

    In recent years, many studies of thyroid-disrupting effects of environmental chemicals have been published. Of special concern is the exposure of pregnant women and infants, as thyroid disruption of the developing organism may have deleterious effects on neurological outcome. Chemicals may exert...... thyroid-disrupting effects, and there is emerging evidence that also phthalates, bisphenol A, brominated flame retardants and perfluorinated chemicals may have thyroid disrupting properties....

  10. Turbulence and disruptions in Tokamaks

    International Nuclear Information System (INIS)

    In the first part of this thesis, the possible explanation of the electron abnormal thermal conductivity with electromagnetic drift modes rather than simply electrostatic is discussed. A variational form is established in non collisional conditions; linear modes principal possibilities are reviewed, then quasilinear theory is used to calculate the transport phenomenon associated to each mode. They are compared to experimental results. Electron abnormal thermal conductibility is not better explained by electromagnetic modes than by electrostatic modes. In the second part, disruptions are examined; experimental manifestations are briefly recalled. Existing interpretations of these phenomenons are reviewed, which are based on magnetic islands non-linear evolution. A detailed analytical study of the case l=1, m=1 is made. Other disruptions are studied; it is shown that the disruptive process is indissociable from sudden apparition of small scale magnetic turbulence. The possibility of such a turbulence is studied. Its predictable effects are compared to experiment. Such a turbulence, is assumed to exist permanently in an attenuated form, which could justify the electronic transport anomalies in quiescent state

  11. Engineering analysis of TFTR disruption

    Energy Technology Data Exchange (ETDEWEB)

    Murray, J.G.; Rothe, K.E.; Bronner, G.

    1984-09-01

    This report covers an engineering approach quantifying the currents, forces, and times, as well as plasma position, for the worst-case disruption based on engineerign circuit assumptions for the plasma. As the plasma moves toward the wall during the current-decay phase of disruption, the wall currents affect the rate of movement and, hence, the decay time. The calculated structure-induced currents differ considerably from those calculated using a presently available criterion, which specifies that the plasma remains stationary in the center of the torus while decaying in 10 ms. This report outlines the method and basis for the engineering calculation used to determine the current and forces as a function of the circuit characteristics. It provides specific calculations for the Tokamak Fusion Test Reactor (TFTR) with variations in parameters such as the thermal decay time, the torus resistance, and plasma temperature during the current decay. The study reviews possible ways to reduce the disruption damage of TFTR by reducing the magnitude of the plasma external field energy that is absorbed by the plasma during the current decay.

  12. Pharmacological disruption of maladaptive memory.

    Science.gov (United States)

    Taylor, Jane R; Torregrossa, Mary M

    2015-01-01

    Many psychiatric disorders are characterized by intrusive, distracting, and disturbing memories that either perpetuate the illness or hinder successful treatment. For example, posttraumatic stress disorder (PTSD) involves such strong reemergence of memories associated with a traumatic event that the individual feels like the event is happening again. Furthermore, drug addiction is characterized by compulsive use and repeated relapse that is often driven by internal memories of drug use and/or by exposure to external stimuli that were associated with drug use. Therefore, identifying pharmacological methods to weaken the strength of maladaptive memories is a major goal of research efforts aimed at finding new treatments for these disorders. The primary mechanism by which memories could be pharmacologically disrupted or altered is through manipulation of memory reconsolidation. Reconsolidation occurs when an established memory is remembered or reactivated, reentering a labile state before again being consolidated into long-term memory storage. Memories are subject to disruption during this labile state. In this chapter we will discuss the preclinical and clinical studies identifying potential pharmacological methods for disrupting the integrity of maladaptive memory to treat mental illness. PMID:25977090

  13. NUMERICAL SIMULATION OF CELLULAR/DENDRITIC PRIMARY SPACING

    Institute of Scientific and Technical Information of China (English)

    W.Q.Zhang; L.Xiao

    2004-01-01

    A numerical model has been established to calculate the primary spacing of cellular or dendritic structure with fluid flow considered. The computing results show that the primary spacing depends on the growing velocity, the temperature gradient on the interface and fluid flow. There is a critical growing velocity for the cell-dendrite transition, which has a relationship with the temperature gradient: Rcr=(3-4)×10-9GT. Fluid flow leads to an increase of the primary spacing for dendritic growth but a decrease for cellular growth,resulting in an instability on the interface.

  14. CD163 positive subsets of blood dendritic cells

    DEFF Research Database (Denmark)

    Maniecki, Maciej Bogdan; Møller, Holger Jon; Moestrup, Søren Kragh;

    2006-01-01

    expression in dendritic cells (DCs) was investigated using multicolor flow cytometry in peripheral blood from 31 healthy donors and 15 HIV-1 patients in addition to umbilical cord blood from 5 newborn infants. Total RNA was isolated from MACS purified DCs and CD163 mRNA was determined with real-time reverse...... transcriptase polymerase chain reaction. The effect of glucocorticoid and phorbol ester stimulation on monocyte and dendritic cell CD163 and CD91 expression was investigated in cell culture of mononuclear cells using multicolor flow cytometry. We identified two CD163+ subsets in human blood with dendritic cell...

  15. Phase field simulation of dendrite growth under convection

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The phase-field model coupled with a flow field was used to simulate the solidification of pure materials by the finite difference method.The effects of initial crystal radius,the space step and the interface thickness on the dendrite growth were studied.Results indicate that the grain grows into an equiaxial dendrite during free flow and into a typical branched structure under forced flow.The radius of an initial crystal can affect the growth of side-branches but not the stability of the dendrite s tip whe...

  16. Follicular Dendritic Cell Sarcoma of the Abdomen: the Imaging Findings

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Tae Wook; Lee, Soon Jin; Song, Hye Jong [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2010-04-15

    Follicular dendritic cell sarcoma is a rare neoplasm that originates from follicular dendritic cells in lymphoid follicles. This disease usually involves the lymph nodes, and especially the head and neck area. Rarely, extranodal sites may be affected, including tonsil, the oral cavity, liver, spleen and the gastrointestinal tract. We report here on the imaging findings of follicular dendritic cell sarcoma of the abdomen that involved the retroperitoneal lymph nodes and colon. It shows as a well-defined, enhancing homogenous mass with internal necrosis and regional lymphadenopathy.

  17. GATA2 regulates dendritic cell differentiation.

    Science.gov (United States)

    Onodera, Koichi; Fujiwara, Tohru; Onishi, Yasushi; Itoh-Nakadai, Ari; Okitsu, Yoko; Fukuhara, Noriko; Ishizawa, Kenichi; Shimizu, Ritsuko; Yamamoto, Masayuki; Harigae, Hideo

    2016-07-28

    Dendritic cells (DCs) are critical immune response regulators; however, the mechanism of DC differentiation is not fully understood. Heterozygous germ line GATA2 mutations induce GATA2-deficiency syndrome, characterized by monocytopenia, a predisposition to myelodysplasia/acute myeloid leukemia, and a profoundly reduced DC population, which is associated with increased susceptibility to viral infections, impaired phagocytosis, and decreased cytokine production. To define the role of GATA2 in DC differentiation and function, we studied Gata2 conditional knockout and haploinsufficient mice. Gata2 conditional deficiency significantly reduced the DC count, whereas Gata2 haploinsufficiency did not affect this population. GATA2 was required for the in vitro generation of DCs from Lin(-)Sca-1(+)Kit(+) cells, common myeloid-restricted progenitors, and common dendritic cell precursors, but not common lymphoid-restricted progenitors or granulocyte-macrophage progenitors, suggesting that GATA2 functions in the myeloid pathway of DC differentiation. Moreover, expression profiling demonstrated reduced expression of myeloid-related genes, including mafb, and increased expression of T-lymphocyte-related genes, including Gata3 and Tcf7, in Gata2-deficient DC progenitors. In addition, GATA2 was found to bind an enhancer element 190-kb downstream region of Gata3, and a reporter assay exhibited significantly reduced luciferase activity after adding this enhancer region to the Gata3 promoter, which was recovered by GATA sequence deletion within Gata3 +190. These results suggest that GATA2 plays an important role in cell-fate specification toward the myeloid vs T-lymphocyte lineage by regulating lineage-specific transcription factors in DC progenitors, thereby contributing to DC differentiation. PMID:27259979

  18. Probiotics, dendritic cells and bladder cancer.

    Science.gov (United States)

    Feyisetan, Oladapo; Tracey, Christopher; Hellawell, Giles O

    2012-06-01

    What's known on the subject? and What does the study add? The suppressor effect of probiotics on superficial bladder cancer is an observed phenomenon but the specific mechanism is poorly understood. The evidence strongly suggests natural killer (NK) cells are the anti-tumour effector cells involved and NK cell activity correlates with the observed anti-tumour effect in mice. It is also known that dendritic cells (DC) cells are responsible for the recruitment and mobilization of NK cells so therefore it may be inferred that DC cells are most likely to be the interphase point at which probiotics act. In support of this, purification of NK cells was associated with a decrease in NK cells activity. The current use of intravesical bacille Calmette-Guérin in the management of superficial bladder cancer is based on the effect of a localised immune response. In the same way, understanding the mechanism of action of probiotics and the role of DC may potentially offer another avenue via which the immune system may be manipulated to resist bladder cancer. Probiotic foods have been available in the UK since 1996 with the arrival of the fermented milk drink (Yakult) from Japan. The presence of live bacterial ingredients (usually lactobacilli species) may confer health benefits when present in sufficient numbers. The role of probiotics in colo-rectal cancer may be related in part to the suppression of harmful colonic bacteria but other immune mechanisms are involved. Anti-cancer effects outside the colon were suggested by a Japanese report of altered rates of bladder tumour recurrence after ingestion of a particular probiotic. Dendritic cells play a central role to the general regulation of the immune response that may be modified by probiotics. The addition of probiotics to the diet may confer benefit by altering rates of bladder tumour recurrence and also alter the response to immune mechanisms involved with the application of intravesical treatments (bacille Calmette

  19. The disruptive instability in Tokamak plasmas

    NARCIS (Netherlands)

    Salzedas, F.J.B.

    2001-01-01

    Studies performed in RTP (Rijnhuizen Tokamak Project) of the most violent and dangerous instability in tokamak plasmas, the major disruption, are presented. A particular class of disruptions is analyzed, namely the density limit disruption, which occur in high density plasmas. The radiative te

  20. Disruptive innovation as an entrepreneurial process

    NARCIS (Netherlands)

    Y. Chandra; S.-J.S. Yang

    2008-01-01

    Research on conditions and causal mechanisms that influence disruptive innovation has been relatively unexplored in the extant research in disruptive innovation. By re-conceptualizing disruptive innovation as an entrepreneurial process at product, firm and industry levels, this paper draws on emergi

  1. Dendritic Kv3.3 potassium channels in cerebellar purkinje cells regulate generation and spatial dynamics of dendritic Ca2+ spikes.

    Science.gov (United States)

    Zagha, Edward; Manita, Satoshi; Ross, William N; Rudy, Bernardo

    2010-06-01

    Purkinje cell dendrites are excitable structures with intrinsic and synaptic conductances contributing to the generation and propagation of electrical activity. Voltage-gated potassium channel subunit Kv3.3 is expressed in the distal dendrites of Purkinje cells. However, the functional relevance of this dendritic distribution is not understood. Moreover, mutations in Kv3.3 cause movement disorders in mice and cerebellar atrophy and ataxia in humans, emphasizing the importance of understanding the role of these channels. In this study, we explore functional implications of this dendritic channel expression and compare Purkinje cell dendritic excitability in wild-type and Kv3.3 knockout mice. We demonstrate enhanced excitability of Purkinje cell dendrites in Kv3.3 knockout mice, despite normal resting membrane properties. Combined data from local application pharmacology, voltage clamp analysis of ionic currents, and assessment of dendritic Ca(2+) spike threshold in Purkinje cells suggest a role for Kv3.3 channels in opposing Ca(2+) spike initiation. To study the physiological relevance of altered dendritic excitability, we measured [Ca(2+)](i) changes throughout the dendritic tree in response to climbing fiber activation. Ca(2+) signals were specifically enhanced in distal dendrites of Kv3.3 knockout Purkinje cells, suggesting a role for dendritic Kv3.3 channels in regulating propagation of electrical activity and Ca(2+) influx in distal dendrites. These findings characterize unique roles of Kv3.3 channels in dendrites, with implications for synaptic integration, plasticity, and human disease. PMID:20357073

  2. Optimization of human dendritic cell sample preparation for mass spectrometry-based proteomic studies.

    Science.gov (United States)

    Zhang, Ying; Bottinelli, Dario; Lisacek, Frédérique; Luban, Jeremy; Strambio-De-Castillia, Caterina; Varesio, Emmanuel; Hopfgartner, Gérard

    2015-09-01

    Dendritic cells (DCs) are specialized leukocytes that orchestrate the adaptive immune response. Mass spectrometry (MS)-based proteomic study of these cells presents technical challenges, especially when the DCs are human in origin due to the paucity of available biological material. Here, to maximize MS coverage of the global human DC proteome, different cell disruption methods, lysis conditions, protein precipitation, and protein pellet solubilization and denaturation methods were compared. Mechanical disruption of DC cell pellets under cryogenic conditions, coupled with the use of RIPA (radioimmunoprecipitation assay) buffer, was shown to be the method of choice based on total protein extraction and on the solubilization and identification of nuclear proteins. Precipitation by acetone was found to be more efficient than that by 10% trichloroacetic acid (TCA)/acetone, allowing in excess of 28% more protein identifications. Although being an effective strategy to eliminate the detergent residue, the acetone wash step caused a loss of protein identifications. However, this potential drawback was overcome by adding 1% sodium deoxycholate into the dissolution buffer, which enhanced both solubility of the precipitated proteins and digestion efficiency. This in turn resulted in 6 to 11% more distinct peptides and 14 to 19% more total proteins identified than using 0.5M triethylammonium bicarbonate alone, with the greatest increase (34%) for hydrophobic proteins. PMID:25983236

  3. Optimization of human dendritic cell sample preparation for mass spectrometry-based proteomics studies

    Science.gov (United States)

    Zhang, Ying; Bottinelli, Dario; Lisacek, Frédérique; Luban, Jeremy; De Castillia, Caterina Strambio; Varesio, Emmanuel; Hopfgartner, Gérard

    2016-01-01

    Dendritic cells (DCs) are specialized leukocytes that orchestrate the adaptive immune response. Mass spectrometry based proteomic study of these cells presents technical challenges, especially when the DCs are human in origin due to the paucity of available biological material. Here, to maximize mass spectrometry coverage of the global human DC proteome, different cell disruption methods, lysis conditions, protein precipitation, and protein pellet solubilisation and denaturation methods were compared. Mechanical disruption of DC cell pellets under cryogenic conditions, coupled with the use of RIPA buffer, was shown to be the method of choice based on total protein extraction and on the solubilisation and identification of nuclear proteins. Precipitation by acetone was found to be more efficient than by 10% TCA/acetone, allowing greater than 28% more protein identifications. Although being an effective strategy to eliminate the detergent residue, the acetone-wash step caused a loss of protein identifications. However, this potential drawback was overcome by adding 1% sodium deoxycholate in the dissolution buffer, which enhanced both solubility of the precipitated proteins and digestion efficiency. This in turn resulted in 6-11% more distinct peptides and 14-19% more total proteins identified than using 0.5M triethylammonium bicarbonate alone with the greatest increase (34%) for hydrophobic proteins. PMID:25983236

  4. Dendritic Cells, Viruses, and the Development of Atopic Disease

    Directory of Open Access Journals (Sweden)

    Jonathan S. Tam

    2012-01-01

    Full Text Available Dendritic cells are important residents of the lung environment. They have been associated with asthma and other inflammatory diseases of the airways. In addition to their antigen-presenting functions, dendritic cells have the ability to modulate the lung environment to promote atopic disease. While it has long been known that respiratory viral infections associate with the development and exacerbation of atopic diseases, the exact mechanisms have been unclear. Recent studies have begun to show the critical importance of the dendritic cell in this process. This paper focuses on these data demonstrating how different populations of dendritic cells are capable of bridging the adaptive and innate immune systems, ultimately leading to the translation of viral illness into atopic disease.

  5. Lithium Dendrite Suppression with UV-Curable Polysilsesquioxane Separator Binders.

    Science.gov (United States)

    Na, Wonjun; Lee, Albert S; Lee, Jin Hong; Hwang, Seung Sang; Kim, Eunkyoung; Hong, Soon Man; Koo, Chong Min

    2016-05-25

    For the first time, an inorganic-organic hybrid polymer binder was used for the coating of hybrid composites on separators to enhance thermal stability and to prevent formation of lithium dendrite in lithium metal batteries. The fabricated hybrid-composite-coated separators exhibited minimal thermal shrinkage compared with the previous composite separators (separators revealed excellent C-rate and cyclability performance due to the prevention of lithium dendrite growth on the lithium anode even after 200 cycles under 0.2-5C (charge-discharge) conditions. The mechanism for lithium dendrite prevention was attributed to exceptional nanoscale surface mechanical properties of the hybrid composite coating layer compared with the lithium metal anode, as the elastic modulus of the hybrid-composite-coated separator far exceeded those of both the lithium metal anode and the required threshold for lithium metal dendrite prevention. PMID:27148625

  6. CUB and Sushi multiple domains 3 regulates dendrite development.

    Science.gov (United States)

    Mizukami, Tomoharu; Kohno, Takao; Hattori, Mitsuharu

    2016-09-01

    CUB and Sushi multiple domains 3 (CSMD3) is a large protein expressed in fetal and adult brain. Recently, mutations of the CSMD3 gene were identified in schizophrenia and autism patients. However, biochemical properties and functions of the CSMD3 protein remain unknown. Here, we demonstrate that CSMD3 is an oligomeric type I transmembrane protein localized in the apical dendrites of hippocampal pyramidal neurons in the postnatal brain. In cultured hippocampal neurons, CSMD3 is expressed only after 7 days in vitro. Overexpression of CSMD3 induced dendritic branching in hippocampal neurons. Regulation of dendritic morphology by CSMD3 depended on the presence of its extracellular region, while CSMD3 intracellular region was dispensable for this activity. These results suggest that CSMD3 acts as a co-receptor of an unidentified membrane protein to regulate dendrite development. Therefore, malfunctions of CSMD3 may be one of the factors in the pathogenesis of psychiatric disorders. PMID:27033969

  7. Observation of dendritic growth under the influence of forced convection

    Science.gov (United States)

    Roshchupkina, O.; Shevchenko, N.; Eckert, S.

    2015-06-01

    The directional solidification of Ga-25wt%In alloys within a Hele-Shaw cell was visualized by X-ray radioscopy. The investigations are focused on the impact of melt convection on the dendritic growth. Natural convection occurs during a bottom up solidification because lighter solute is rejected during crystallization. Forced convection was produced by a specific electromagnetic pump. The direction of forced melt flow is almost horizontal at the solidification front. Melt flow induces various effects on grain morphology primarily caused by convective transport of solute, such as a facilitation of the growth of primary trunks or lateral branches, dendrite remelting, fragmentation or freckle formation depending on the dendrite orientation, the flow direction and intensity. Forced flow eliminates solutal plumes and damps local fluctuations of solute. A preferential growth of the secondary arms occurs at the upstream side of the dendrites, whereas high solute concentration at the downstream side inhibits the formation of secondary branches.

  8. Supramolecular effects in dendritic systems containing photoactive groups

    Directory of Open Access Journals (Sweden)

    GIANLUCA CAMILLO AZZELLINI

    2000-03-01

    Full Text Available In this article are described dendritic structures containing photoactive groups at the surface or in the core. The observed supramolecular effects can be attributed to the nature of the photoactive group and their location in the dendritic architecture. The peripheric azobenzene groups in these dendrimeric compounds can be regarded as single residues that retain the spectroscopic and photochemical properties of free azobenzene moiety. The E and Z forms of higher generation dendrimer, functionalized with azobenzene groups, show different host ability towards eosin dye, suggesting the possibility of using such dendrimer in photocontrolled host-guest systems. The photophysical properties of many dendritic-bipyridine ruthenium complexes have been investigated. Particularly in aerated medium more intense emission and a longer excited-state lifetime are observed as compared to the parent unsubstituted bipyridine ruthenium complexes. These differences can be attributed to a shielding effect towards dioxygen quenching originated by the dendritic branches.

  9. Actin Remodeling and Polymerization Forces Control Dendritic Spine Morphology

    CERN Document Server

    Miermans, Karsten; Storm, Cornelis; Hoogenraad, Casper

    2015-01-01

    Dendritic spines are small membranous structures that protrude from the neuronal dendrite. Each spine contains a synaptic contact site that may connect its parent dendrite to the axons of neighboring neurons. Dendritic spines are markedly distinct in shape and size, and certain types of stimulation prompt spines to evolve, in fairly predictable fashion, from thin nascent morphologies to the mushroom-like shapes associated with mature spines. This striking progression is coincident with the (re)configuration of the neuronal network during early development, learning and memory formation, and has been conjectured to be part of the machinery that encodes these processes at the scale of individual neuronal connections. It is well established that the structural plasticity of spines is strongly dependent upon the actin cytoskeleton inside the spine. A general framework that details the precise role of actin in directing the transitions between the various spine shapes is lacking. We address this issue, and present...

  10. Environmental alkylphenols modulate cytokine expression in plasmacytoid dendritic cells.

    Directory of Open Access Journals (Sweden)

    Chih-Hsing Hung

    Full Text Available BACKGROUND: Alkylphenols, such as nonylphenol (NP and 4-octylphenol (4-OP, have the potential to disturb immune system due to their weak estrogen-like activity, an effect with potential serious public health impact due to the worldwide distribution of these substances. Plasmacytoid dendritic cells (PDCs can secrete large amounts of type I IFNs and are critical in immune regulation. However, there has been limited study about the influence of alkylphenols on the function of pDCs. OBJECTIVE: The aim of this study was to examine the effect of alkylphenols on pDC functions in vitro and in vivo and then further explored the involved signaling pathways and epigenetic changes. METHODS: Circulating pDCs from human peripheral blood mononuclear cells were treated with alkylphenols with or without CpG stimulation. Alkylphenol-associated cytokine responses, signaling events, histone modifications and viral activity were further examined. In NP-exposed mice, the effect of NP on splenic pDC function and allergic lung inflammation were also assessed. RESULTS: The results showed that NP increased the expression of TNF-α, but suppressed IL-10 production in the range of physiological doses, concomitant with activation of the MKK3/6-p38 signaling pathway and enhanced levels of acetylated histone 3 as well as histone 4 at the TNFA gene locus. Further, in CpG-stimulated pDCs, NP suppressed type I IFNs production, associated with down-regulation of IRF-7 and MKK1/2-ERK-Elk-1 pathways and led to the impaired anti-enterovirus 71 activity in vitro. Additionally, splenic pDCs from NP-exposed mice showed similar cytokine changes upon CpG stimulation under conditions relevant to route and level of exposure in humans. NP treatment also enhanced allergic lung inflammation in vivo. CONCLUSION: Alkylphenols may influence pDCs' functions via their abilities to induce expression of a pro-inflammatory cytokine, TNF-α, and to suppress regulatory cytokines, including IL-10, IFN

  11. Follicular dendritic cell sarcoma of the pharyngeal region

    OpenAIRE

    HU, TENGPENG; Wang, Xinhua; Yu, Chang; YAN, JIAQIN; ZHANG, XUNDONG; Li, Ling; Li, Xin; Zhang, Lei; Wu, Jingjing; MA, WANG; Li, Wencai; Wang, Guannan; ZHAO, WUGAN; GAO, XIANZHENG; Zhang, Dandan

    2013-01-01

    Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm arising most commonly from follicular dendritic cells in the lymph nodes. It is exceedingly rare in extranodal sites, particularly in the pharyngeal region. The present study reports 3 cases occurring in the pharyngeal region. Case 1 had tonsil and cervical lymph node involvement, while case 3 also had tonsil involvement. Cases 1 and 3 relapsed locally at 3 and 17 months after surgery, respectively. Case 2 was diagnosed with a tumor ...

  12. Human plasmacytoid dendritic cells: from molecules to intercellular communication network

    OpenAIRE

    Till Sebastian Manuel Mathan; Carl Gustav Figdor; Sonja Ingrid Buschow

    2013-01-01

    Plasmacytoid Dendritic Cells (pDCs) are a specific subset of naturally occurring dendritic cells, that secrete large amounts of Type I interferon and play an important role in the immune response against viral infection. Several studies have highlighted that they are also effective antigen presenting cells (APCs), making them an interesting target for immunotherapy against cancer. However, the modes of action of pDCs are not restricted to antigen presentation and IFN secretion alone. In this ...

  13. Human Plasmacytoid Dendritic Cells: From Molecules to Intercellular Communication Network

    OpenAIRE

    Mathan, Till S. M.; Figdor, Carl G.; Buschow, Sonja I.

    2013-01-01

    Plasmacytoid dendritic cells (pDCs) are a specific subset of naturally occurring dendritic cells, that secrete large amounts of Type I interferon and play an important role in the immune response against viral infection. Several studies have highlighted that they are also effective antigen presenting cells, making them an interesting target for immunotherapy against cancer. However, the modes of action of pDCs are not restricted to antigen presentation and IFN secretion alone. In this review ...

  14. Dendritic bundles, minicolumns, columns, and cortical output units

    Directory of Open Access Journals (Sweden)

    Giorgio Innocenti

    2010-03-01

    Full Text Available The search for the fundamental building block of the cerebral cortex has highlighted three structures, perpendicular to the cortical surface: i columns of neurons with radially invariant response properties, e.g., receptive field position, sensory modality, stimulus orientation or direction, frequency tuning etc. ii minicolumns of radially aligned cell bodies and iii bundles, constituted by the apical dendrites of pyramidal neurons with cell bodies in different layers. The latter were described in detail, and sometimes quantitatively, in several species and areas. It was recently suggested that the dendritic bundles consist of apical dendrites belonging to neurons projecting their axons to specific targets. We review the concept above and suggest that another structural and computational unit of cerebral cortex is the cortical output unit (COU, i.e. an assembly of bundles of apical dendrites and their parent cell bodies including each of the outputs to distant cortical or subcortical structures, of a given cortical locus (area or part of an area. This somato-dendritic assembly receives inputs some of which are common to the whole assembly and determine its radially invariant response properties, others are specific to one or more dendritic bundles, and determine the specific response signature of neurons in the different cortical layers and projecting to different targets.

  15. Disruptive Innovation in Numerical Hydrodynamics

    Energy Technology Data Exchange (ETDEWEB)

    Waltz, Jacob I. [Los Alamos National Laboratory

    2012-09-06

    We propose the research and development of a high-fidelity hydrodynamic algorithm for tetrahedral meshes that will lead to a disruptive innovation in the numerical modeling of Laboratory problems. Our proposed innovation has the potential to reduce turnaround time by orders of magnitude relative to Advanced Simulation and Computing (ASC) codes; reduce simulation setup costs by millions of dollars per year; and effectively leverage Graphics Processing Unit (GPU) and future Exascale computing hardware. If successful, this work will lead to a dramatic leap forward in the Laboratory's quest for a predictive simulation capability.

  16. Disruptive innovation for social change.

    Science.gov (United States)

    Christensen, Clayton M; Baumann, Heiner; Ruggles, Rudy; Sadtler, Thomas M

    2006-12-01

    Countries, organizations, and individuals around the globe spend aggressively to solve social problems, but these efforts often fail to deliver. Misdirected investment is the primary reason for that failure. Most of the money earmarked for social initiatives goes to organizations that are structured to support specific groups of recipients, often with sophisticated solutions. Such organizations rarely reach the broader populations that could be served by simpler alternatives. There is, however, an effective way to get to those underserved populations. The authors call it "catalytic innovation." Based on Clayton Christensen's disruptive-innovation model, catalytic innovations challenge organizational incumbents by offering simpler, good-enough solutions aimed at underserved groups. Unlike disruptive innovations, though, catalytic innovations are focused on creating social change. Catalytic innovators are defined by five distinct qualities. First, they create social change through scaling and replication. Second, they meet a need that is either overserved (that is, the existing solution is more complex than necessary for many people) or not served at all. Third, the products and services they offer are simpler and cheaper than alternatives, but recipients view them as good enough. Fourth, they bring in resources in ways that initially seem unattractive to incumbents. And fifth, they are often ignored, put down, or even encouraged by existing organizations, which don't see the catalytic innovators' solutions as viable. As the authors show through examples in health care, education, and economic development, both nonprofit and for-profit groups are finding ways to create catalytic innovation that drives social change.

  17. CTLA-4 blockade during dendritic cell based booster vaccination influences dendritic cell survival and CTL expansion

    DEFF Research Database (Denmark)

    Pedersen, Anders E; Ronchese, Franca

    2007-01-01

    Dendritic cells (DCs) are potent antigen-presenting cells and critical for the priming of CD8+ T cells. Therefore the use of these cells as adjuvant cells has been tested in a large number of experimental and clinical vaccination studies, in particular cancer vaccine studies. A number of protocols....... We have previously reported that DCs loaded with specific antigens are eliminated by antigen specific CTLs in vivo and that this elimination affects the potential for in vivo CTL generation. We now show that CTLA-4 blockade increases the number of DC vaccine induced LCMV gp33 specific CTLs...

  18. Numerical Simulation of Dendritic Growth of Continuously Cast High Carbon Steel

    Science.gov (United States)

    Wang, Weiling; Luo, Sen; Zhu, Miaoyong

    2015-01-01

    Considering the influence of the latent heat released during the solidification of high carbon liquid steel, a cellular automaton (CA) model coupled with the heat transfer was developed to investigate the growth of equiaxed dendrites which is controlled by the solute diffusion during the continuous casting process. Additionally, the growth of columnar dendrites and primary dendrite arm spacings were predicted and measured. The results show that the CA model is able to describe the growth behavior of equiaxed dendrites, especially at 5 K to 7 K melt undercoolings, and the approach adjusting the cooling medium temperature is reliable to keep the undercooling condition stable for equiaxed dendrites although its hysteresis is reinforced as the pre-set undercooling increases. With the increase of the melt undercooling, the growth of equiaxed dendrites becomes faster, and the thickness of dendritic arms increases slightly, however, the thickness of the diffusion layer in front of dendritic tips keeps constant. The growth of thin and tiny columnar dendrites will be confined due to the competition and absorbed by neighboring strong columnar dendrites, giving rise to the coarsening of columnar dendrites, which is observed both from the experimental observation and the numerical simulation. With the decrease of the cooling intensity, columnar dendrites get sparser, primary dendrite arm spacings increase, and secondary dendritic arms become undeveloped.

  19. Activated protein C modulates the proinflammatory activity of dendritic cells

    Directory of Open Access Journals (Sweden)

    Matsumoto T

    2015-05-01

    Full Text Available Takahiro Matsumoto,1,2* Yuki Matsushima,1* Masaaki Toda,1 Ziaurahman Roeen,1 Corina N D'Alessandro-Gabazza,1,5 Josephine A Hinneh,1 Etsuko Harada,1,3 Taro Yasuma,4 Yutaka Yano,4 Masahito Urawa,1,5 Tetsu Kobayashi,5 Osamu Taguchi,5 Esteban C Gabazza1 1Department of Immunology, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, 2BONAC Corporation, BIO Factory 4F, Fukuoka, 3Iwade Research Institute of Mycology, 4Department of Endocrinology, Diabetes and Metabolism, 5Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan *These authors contributed equally to this work Background: Previous studies have demonstrated the beneficial activity of activated protein C in allergic diseases including bronchial asthma and rhinitis. However, the exact mechanism of action of activated protein C in allergies is unclear. In this study, we hypothesized that pharmacological doses of activated protein C can modulate allergic inflammation by inhibiting dendritic cells. Materials and methods: Dendritic cells were prepared using murine bone marrow progenitor cells and human peripheral monocytes. Bronchial asthma was induced in mice that received intratracheal instillation of ovalbumin-pulsed dendritic cells. Results: Activated protein C significantly increased the differentiation of tolerogenic plasmacytoid dendritic cells and the secretion of type I interferons, but it significantly reduced lipopolysaccharide-mediated maturation and the secretion of inflammatory cytokines in myeloid dendritic cells. Activated protein C also inhibited maturation and the secretion of inflammatory cytokines in monocyte-derived dendritic cells. Activated protein C-treated dendritic cells were less effective when differentiating naïve CD4 T-cells from Th1 or Th2 cells, and the cellular effect of activated protein C was mediated by its receptors. Mice that received adoptive transfer of activated protein C

  20. Deletion of collapsin response mediator protein 4 results in abnormal layer thickness and elongation of mitral cell apical dendrites in the neonatal olfactory bulb.

    Science.gov (United States)

    Tsutiya, Atsuhiro; Watanabe, Hikaru; Nakano, Yui; Nishihara, Masugi; Goshima, Yoshio; Ohtani-Kaneko, Ritsuko

    2016-05-01

    Collapsin response mediator protein 4 (CRMP4), a member of the CRMP family, is involved in the pathogenesis of neurodevelopmental disorders such as schizophrenia and autism. Here, we first compared layer thickness of the olfactory bulb between wild-type (WT) and CRMP4-knockout (KO) mice. The mitral cell layer (MCL) was significantly thinner, whereas the external plexiform layer (EPL) was significantly thicker in CRMP4-KO mice at postnatal day 0 (PD0) compared with WTs. However, differences in layer thickness disappeared by PD14. No apoptotic cells were found in the MCL, and the number of mitral cells (MCs) identified with a specific marker (i.e. Tbx21 antibody) did not change in CRMP4-KO neonates. However, DiI-tracing showed that the length of mitral cell apical dendrites was greater in CRMP4-KO neonates than in WTs. In addition, expression of CRMP4 mRNA in WT mice was most abundant in the MCL at PD0 and decreased afterward. These results suggest that CRMP4 contributes to dendritic elongation. Our in vitro studies showed that deletion or knockdown of CRMP4 resulted in enhanced growth of MAP2-positive neurites, whereas overexpression of CRMP4 reduced their growth, suggesting a new role for CRMP4 as a suppressor of dendritic elongation. Overall, our data suggest that disruption of CRMP4 produces a temporary alteration in EPL thickness, which is constituted mainly of mitral cell apical dendrites, through the enhanced growth of these dendrites. PMID:26739921

  1. Transcriptional regulation of dendritic cell diversity.

    Science.gov (United States)

    Chopin, Michaël; Allan, Rhys S; Belz, Gabrielle T

    2012-01-01

    Dendritic cells (DCs) are specialized antigen presenting cells that are exquisitely adapted to sense pathogens and induce the development of adaptive immune responses. They form a complex network of phenotypically and functionally distinct subsets. Within this network, individual DC subsets display highly specific roles in local immunosurveillance, migration, and antigen presentation. This division of labor amongst DCs offers great potential to tune the immune response by harnessing subset-specific attributes of DCs in the clinical setting. Until recently, our understanding of DC subsets has been limited and paralleled by poor clinical translation and efficacy. We have now begun to unravel how different DC subsets develop within a complex multilayered system. These findings open up exciting possibilities for targeted manipulation of DC subsets. Furthermore, ground-breaking developments overcoming a major translational obstacle - identification of similar DC populations in mouse and man - now sets the stage for significant advances in the field. Here we explore the determinants that underpin cellular and transcriptional heterogeneity within the DC network, how these influence DC distribution and localization at steady-state, and the capacity of DCs to present antigens via direct or cross-presentation during pathogen infection.

  2. Deciphering dendritic cell heterogenity in immunity

    Directory of Open Access Journals (Sweden)

    Michaël eChopin

    2012-02-01

    Full Text Available Dendritic cells (DCs are specialized antigen presenting cells that are exquisitely adapted to sense pathogens and induce the development of adaptive immune responses. They form a complex network of phenotypically and functionally distinct subsets. Within this network, individual DC subsets display highly specific roles in local immunosurveillance, migration and antigen presentation. This division of labor amongst DCs offers great potential to tune the immune response by harnessing subset-specific attributes of DCs in the clinical setting. Until recently, our understanding of DC subsets has been limited and paralleled by poor clinical translation and efficacy. We have now begun to unravel how different DC subsets develop within a complex multilayered system. These finding open up exciting possibilities for targeted manipulation of DC subsets. Furthermore, ground-breaking developments overcoming a major translational obstacle – identification of similar DC populations in mouse and man – now set the stage for significant advances in the field. Here we explore the determinants that underpin cellular and transcriptional heterogeneity within the DC network, how these influence DC distribution and localization at steady-state, and the capacity of DCs to present antigens via direct or cross-presentation during pathogen infection.

  3. Dendritic Cells in the Cancer Microenvironment

    Directory of Open Access Journals (Sweden)

    Yang Ma, Galina V. Shurin, Zhu Peiyuan, Michael R. Shurin

    2013-01-01

    Full Text Available The complexity of the tumor immunoenvironment is underscored by the emergence and discovery of different subsets of immune effectors and regulatory cells. Tumor-induced polarization of immune cell differentiation and function makes this unique environment even more intricate and variable. Dendritic cells (DCs represent a special group of cells that display different phenotype and activity at the tumor site and exhibit differential pro-tumorigenic and anti-tumorigenic functions. DCs play a key role in inducing and maintaining the antitumor immunity, but in the tumor environment their antigen-presenting function may be lost or inefficient. DCs might be also polarized into immunosuppressive/tolerogenic regulatory DCs, which limit activity of effector T cells and support tumor growth and progression. Although various factors and signaling pathways have been described to be responsible for abnormal functioning of DCs in cancer, there are still no feasible therapeutic modalities available for preventing or reversing DC malfunction in tumor-bearing hosts. Thus, better understanding of DC immunobiology in cancer is pivotal for designing novel or improved therapeutic approaches that will allow proper functioning of DCs in patients with cancer.

  4. Follicular dendritic cells in health and disease

    Directory of Open Access Journals (Sweden)

    Mohey Eldin M El Shikh

    2012-09-01

    Full Text Available Follicular dendritic cells (FDCs are unique immune cells that contribute to the regulation of humoral immune responses. These cells are located in the B cell follicles of secondary lymphoid tissues where they trap and retain antigens (Ags in the form of highly immunogenic immune complexes (ICs consisting of Ag plus specific antibody (Ab and/or complement proteins. FDCs multimerise Ags and present them polyvalently to B cells in periodically arranged arrays that extensively crosslink the B cell receptors for Ag (BCRs. FDC-Fc-gamma-RIIB mediates IC periodicity, and FDC-Ag presentation combined with other soluble and membrane bound signals contributed by FDCs, like FDC-BAFF, -IL-6 and -C4bBP, are essential for the induction of the germinal centre (GC reaction, the maintenance of serological memory, and the remarkable ability of FDC-Ags to induce specific Ab responses in the absence of cognate T cell help. On the other hand, FDCs play a negative role in several disease conditions including chronic inflammatory diseases, autoimmune diseases, HIV/AIDS, prion diseases and follicular lymphomas. Compared to other accessory immune cells, FDCs have received little attention, and their functions have not been fully elucidated. This review gives an overview of FDC structure, and recapitulates our current knowledge on the immunoregulatory functions of FDCs in health and disease. A better understanding of FDCs should permit better regulation of Ab responses to suit the therapeutic manipulation of regulated and dysregulated immune responses.

  5. Follicular dendritic cells in health and disease.

    Science.gov (United States)

    El Shikh, Mohey Eldin M; Pitzalis, Costantino

    2012-01-01

    Follicular dendritic cells (FDCs) are unique immune cells that contribute to the regulation of humoral immune responses. These cells are located in the B-cell follicles of secondary lymphoid tissues where they trap and retain antigens (Ags) in the form of highly immunogenic immune complexes (ICs) consisting of Ag plus specific antibody (Ab) and/or complement proteins. FDCs multimerize Ags and present them polyvalently to B-cells in periodically arranged arrays that extensively crosslink the B-cell receptors for Ag (BCRs). FDC-FcγRIIB mediates IC periodicity, and FDC-Ag presentation combined with other soluble and membrane bound signals contributed by FDCs, like FDC-BAFF, -IL-6, and -C4bBP, are essential for the induction of the germinal center (GC) reaction, the maintenance of serological memory, and the remarkable ability of FDC-Ags to induce specific Ab responses in the absence of cognate T-cell help. On the other hand, FDCs play a negative role in several disease conditions including chronic inflammatory diseases, autoimmune diseases, HIV/AIDS, prion diseases, and follicular lymphomas. Compared to other accessory immune cells, FDCs have received little attention, and their functions have not been fully elucidated. This review gives an overview of FDC structure, and recapitulates our current knowledge on the immunoregulatory functions of FDCs in health and disease. A better understanding of FDCs should permit better regulation of Ab responses to suit the therapeutic manipulation of regulated and dysregulated immune responses. PMID:23049531

  6. Sodium pump organization in dendritic spines.

    Science.gov (United States)

    Blom, Hans; Bernhem, Kristoffer; Brismar, Hjalmar

    2016-10-01

    Advancement in fluorescence imaging with the invention of several super-resolution microscopy modalities (e.g., PALM/STORM and STED) has opened up the possibility of deciphering molecular distributions on the nanoscale. In our quest to better elucidate postsynaptic protein distribution in dendritic spines, we have applied these nanoscopy methods, where generated results could help improve our understanding of neuronal functions. In particular, we have investigated the principal energy transformer in the brain, i.e., the [Formula: see text]-ATPase (or sodium pump), an essential protein responsible for maintaining resting membrane potential and a major controller of intracellular ion homeostasis. In these investigations, we have focused on estimates of protein amount, giving assessments of how variations may depend on labeling strategies, sample analysis, and choice of nanoscopic imaging method, concluding that all can be critical factors for quantification. We present a comparison of these results and discuss the influences this may have for homeostatic sodium regulation in neurons and energy consumption. PMID:27175374

  7. Baicalin induced dendritic cell apoptosis in vitro

    Directory of Open Access Journals (Sweden)

    Huahua eZhang

    2011-03-01

    Full Text Available This study was aimed to investigate the effects of Baicalin (BA, a major flavonoid constituent found in the herb Baikal skullcap, on dendritic cells (DCs. DCs were generated by culturing murine bone marrow cells for 6 days with granulocyte-macrophage colony-stimulating factor and interleukin-4, and lipopolysaccharide (LPS was added on day 5 to stimulate DCs maturation. The expression levels of DC maturity markers (CD80/CD86 were assessed by flow cytometry using direct immunofluorescence method. Interleukin-12 (IL-12 levels in the culture supernatants were assayed by ELISA. Apoptosis of DCs was analyzed by flow cytometry after Annexin V/propidium iodide staining. The mitochondrial membrane potential changes were measured by using the J-aggregate forming lipophilic cation 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1. Exposure of DCs to BA (2-50 microM during bone marrow cell differentiation showed no effects on the up-regulation of CD80/CD86 expression on DCs in response to LPS stimulation, but reduced DCs recovery by inducing apoptosis, and significantly inhibited the release of IL-12 to culture supernatants. BA induced DC apoptosis in a time- and dose-dependent way, and immature DCs were more sensitive for BA-induced apoptosis than mature DC. BA also induced mitochondrial membrane potential changes in DCs. These results demonstrate that BA induces selective apoptosis in immature DCs possibly through mitochondria-mediated pathway.

  8. Current concepts in neuroendocrine disruption.

    Science.gov (United States)

    León-Olea, Martha; Martyniuk, Christopher J; Orlando, Edward F; Ottinger, Mary Ann; Rosenfeld, Cheryl S; Wolstenholme, Jennifer T; Trudeau, Vance L

    2014-07-01

    In the last few years, it has become clear that a wide variety of environmental contaminants have specific effects on neuroendocrine systems in fish, amphibians, birds and mammals. While it is beyond the scope of this review to provide a comprehensive examination of all of these neuroendocrine disruptors, we will focus on select representative examples. Organochlorine pesticides bioaccumulate in neuroendocrine areas of the brain that directly regulate GnRH neurons, thereby altering the expression of genes downstream of GnRH signaling. Organochlorine pesticides can also agonize or antagonize hormone receptors, adversely affecting crosstalk between neurotransmitter systems. The impacts of polychlorinated biphenyls are varied and in many cases subtle. This is particularly true for neuroedocrine and behavioral effects of exposure. These effects impact sexual differentiation of the hypothalamic-pituitary-gonadal axis, and other neuroendocrine systems regulating the thyroid, metabolic, and stress axes and their physiological responses. Weakly estrogenic and anti-androgenic pollutants such as bisphenol A, phthalates, phytochemicals, and the fungicide vinclozolin can lead to severe and widespread neuroendocrine disruptions in discrete brain regions, including the hippocampus, amygdala, and hypothalamus, resulting in behavioral changes in a wide range of species. Behavioral features that have been shown to be affected by one or more these chemicals include cognitive deficits, heightened anxiety or anxiety-like, sociosexual, locomotor, and appetitive behaviors. Neuroactive pharmaceuticals are now widely detected in aquatic environments and water supplies through the release of wastewater treatment plant effluents. The antidepressant fluoxetine is one such pharmaceutical neuroendocrine disruptor. Fluoxetine is a selective serotonin reuptake inhibitor that can affect multiple neuroendocrine pathways and behavioral circuits, including disruptive effects on reproduction and

  9. DMPD: Plasmacytoid dendritic cells: sensing nucleic acids in viral infection andautoimmune diseases. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18641647 Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and... (.csml) Show Plasmacytoid dendritic cells: sensing nucleic acids in viral infection andautoimmune diseases.... PubmedID 18641647 Title Plasmacytoid dendritic cells: sensing nucleic acids in v

  10. Multistage Logistic Network Optimization under Disruption Risk

    OpenAIRE

    Rusman, Muhammad

    2013-01-01

    Getting over disruptions risk has been a challenging issue for many companies under the globalization that will link to potential external source such as demand uncertainties, natural disasters, and terrorist attacks. The disruption is an unexpected event that disturbs normal flows of products and materials within a supply chain. The disruption at one members of supply chain will propagate the offers and finally affect significant impacts on the entire chain. If we look back...

  11. Disrupted Sleep: From Molecules to Cognition

    OpenAIRE

    Someren, E.J.W.; Cirelli, C.; Dijk, D.-J.; Van Cauter, E; Schwartz, Sophie; Chee, M. W. L.

    2015-01-01

    Although the functions of sleep remain to be fully elucidated, it is clear that there are far-reaching effects of its disruption, whether by curtailment for a single night, by a few hours each night over a long period, or by disruption in sleep continuity. Epidemiological and experimental studies of these different forms of sleep disruption show deranged physiology from subcellular levels to complex affective behavior. In keeping with the multifaceted influence of sleep on health and well-bei...

  12. Disrupted Sleep: From Molecules to Cognition

    OpenAIRE

    Van Someren, Eus J. W.; Cirelli, Chiara; Dijk, Derk-Jan; Van Cauter, Eve; Schwartz, Sophie; Chee, Michael W. L.

    2015-01-01

    UNLABELLED: Although the functions of sleep remain to be fully elucidated, it is clear that there are far-reaching effects of its disruption, whether by curtailment for a single night, by a few hours each night over a long period, or by disruption in sleep continuity. Epidemiological and experimental studies of these different forms of sleep disruption show deranged physiology from subcellular levels to complex affective behavior. In keeping with the multifaceted influence of sleep on health ...

  13. Disruption management in passenger railway transportation.

    OpenAIRE

    Jespersen-Groth, J.; Potthoff, Daniel; Clausen, J.; Huisman, Dennis; Kroon, Leo; Maróti, Gábor; Nielsen, M.N.

    2007-01-01

    textabstractThis paper deals with disruption management in passenger railway transportation. In the disruption management process, many actors belonging to different organizations play a role. In this paper we therefore describe the process itself and the roles of the different actors. Furthermore, we discuss the three main subproblems in railway disruption management: timetable adjustment, and rolling stock and crew re-scheduling. Next to a general description of these problems, we give an o...

  14. Towards a Framework of Digital Platform Disruption

    OpenAIRE

    Kazan, Erol; Tan, Chee-Wee; Lim, Eric T. K.

    2014-01-01

    Digital platforms are disruptive information technology (IT) artifacts that erode conventional business logic associated with traditional market structures. This paper presents a framework for examining the disruptive potential of digital platforms whereby we postulate that the strategic interplay of governance regimes and platform layers is deterministic of whether disruptive derivatives are permitted to flourish. This framework has been employed in a comparative case study betwe...

  15. Catastrophic disruption experiments: Recent results

    Science.gov (United States)

    Martelli, G.; Ryan, E. V.; Nakamura, A. M.; Giblin, I.

    1994-01-01

    This paper presents a review of the progress in the field of catastrophic disruption experiments over the past 4 years, since the publication of the review paper by Fujiwara et al. (1989). We describe the development of new techniques to produce shattering impacts relevant to the study of the collisional evolution of the asteroids, and summarize the results from numerous experiments which have been performed to date, using a variety of materials for both the impactor and the targets. Some of these, such as ice-on-ice, loose aggregates and pressurized targets, are quite new and have provided novel and exciting results. Some of the gaps existing previously in the data on fragment ejection-angle distributions, as well as translational and rotational velocity fields (including fine fragments) have been filled, and these new results will be surveyed.

  16. Disrupting Entanglement of Black Holes

    CERN Document Server

    Leichenauer, Stefan

    2014-01-01

    We study entanglement in thermofield double states of strongly coupled CFTs by analyzing two-sided Reissner-Nordstrom solutions in AdS. The central object of study is the mutual information between a pair of regions, one on each asymptotic boundary of the black hole. For large regions the mutual information is positive and for small ones it vanishes; we compute the critical length scale, which goes to infinity for extremal black holes, of the transition. We also generalize the butterfly effect of Shenker and Stanford to a wide class of charged black holes, showing that mutual information is disrupted upon perturbing the system and waiting for a time of order $\\log E/\\delta E$ in units of the temperature. We conjecture that the parametric form of this timescale is universal.

  17. Human intestinal dendritic cells as controllers of mucosal immunity

    Directory of Open Access Journals (Sweden)

    David Bernardo

    2013-06-01

    Full Text Available Dendritic cells are the most potent, professional antigen-presenting cells in the body; following antigen presentation they control the type (proinflammatory/regulatory of immune response that will take place, as well as its location. Given their high plasticity and maturation ability in response to local danger signals derived from innate immunity, dendritic cells are key actors in the connection between innate immunity and adaptive immunity responses. In the gut dendritic cells control immune tolerance mechanisms against food and/or commensal flora antigens, and are also capable of initiating an active immune response in the presence of invading pathogens. Dendritic cells are thus highly efficient in controlling the delicate balance between tolerance and immunity in an environment so rich in antigens as the gut, and any factor involving these cells may impact their function, ultimately leading to the development of bowel conditions such as celiac disease or inflammatory bowel disease. In this review we shall summarize our understanding of human intestinal dendritic cells, their ability to express and induce migration markers, the various environmental factors modulating their properties, their subsets in the gut, and the problems entailed by their study, including identification strategies, differences between humans and murine models, and phenotypical variations along the gastrointestinal tract.

  18. Human intestinal dendritic cells as controllers of mucosal immunity.

    Science.gov (United States)

    Bernardo, David

    2013-01-01

    Dendritic cells are the most potent, professional antigen-presenting cells in the body; following antigen presentation they control the type (proinflammatory/regulatory) of immune response that will take place, as well as its location. Given their high plasticity and maturation ability in response to local danger signals derived from innate immunity, dendritic cells are key actors in the connection between innate immunity and adaptive immunity responses. In the gut dendritic cells control immune tolerance mechanisms against food and/or commensal flora antigens, and are also capable of initiating an active immune response in the presence of invading pathogens. Dendritic cells are thus highly efficient in controlling the delicate balance between tolerance and immunity in an environment so rich in antigens as the gut, and any factor involving these cells may impact their function, ultimately leading to the development of bowel conditions such as celiac disease or inflammatory bowel disease. In this review we shall summarize our understanding of human intestinal dendritic cells, their ability to express and induce migration markers, the various environmental factors modulating their properties, their subsets in the gut, and the problems entailed by their study, including identification strategies, differences between humans and murine models, and phenotypical variations along the gastrointestinal tract.

  19. Dendrite growth characteristics within liquid Fe-Sb alloy

    Institute of Scientific and Technical Information of China (English)

    WANG WeiLi; Lü YongJun; QIN HaiYan; WEI BingBo

    2009-01-01

    Bulk samples and small droplets of liquid Fe-10%Sb alloys are undercooled up to 429 K (0.24TL) and 568 K (0.32 TL), respectively, with glass fluxing and free fall techniques. The high undercooling does not change the phase constitution, and only the αFe solid solution is found in the rapidly solidified alloy.The experimental results show that when the undercooling is below 296 K, the growth velocity of αFe dendrite rises exponentially with the increase of undercooling and reaches a maximum value 1.38 m/s.Subsequently, the growth velocity begins to decrease if undercooling further increases. The αFe phase grows into coarse dendrites under small undercooling conditions, whereas it becomes vermicular dendrites in highly undercooled melts. The solute trapping is closely related to the dendrite growth velocity and cooling rate rather than undercooling. Although the solute trapping can be remarkably suppressed by the rapid dendrite growth, the segregationless solidification is not observed in the present experiments due to the large solidification temperature range.

  20. Dendrite growth characteristics within liquid Fe-Sb alloy

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Bulk samples and small droplets of liquid Fe-10%Sb alloys are undercooled up to 429 K (0.24TL) and 568 K (0.32TL), respectively, with glass fluxing and free fall techniques. The high undercooling does not change the phase constitution, and only the αFe solid solution is found in the rapidly solidified alloy. The experimental results show that when the undercooling is below 296 K, the growth velocity of αFe dendrite rises exponentially with the increase of undercooling and reaches a maximum value 1.38 m/s. Subsequently, the growth velocity begins to decrease if undercooling further increases. The αFe phase grows into coarse dendrites under small undercooling conditions, whereas it becomes vermicular dendrites in highly undercooled melts. The solute trapping is closely related to the dendrite growth velocity and cooling rate rather than undercooling. Although the solute trapping can be remarkably suppressed by the rapid dendrite growth, the segregationless solidification is not observed in the present experiments due to the large solidification temperature range.

  1. Location-dependent excitatory synaptic interactions in pyramidal neuron dendrites.

    Directory of Open Access Journals (Sweden)

    Bardia F Behabadi

    Full Text Available Neocortical pyramidal neurons (PNs receive thousands of excitatory synaptic contacts on their basal dendrites. Some act as classical driver inputs while others are thought to modulate PN responses based on sensory or behavioral context, but the biophysical mechanisms that mediate classical-contextual interactions in these dendrites remain poorly understood. We hypothesized that if two excitatory pathways bias their synaptic projections towards proximal vs. distal ends of the basal branches, the very different local spike thresholds and attenuation factors for inputs near and far from the soma might provide the basis for a classical-contextual functional asymmetry. Supporting this possibility, we found both in compartmental models and electrophysiological recordings in brain slices that the responses of basal dendrites to spatially separated inputs are indeed strongly asymmetric. Distal excitation lowers the local spike threshold for more proximal inputs, while having little effect on peak responses at the soma. In contrast, proximal excitation lowers the threshold, but also substantially increases the gain of distally-driven responses. Our findings support the view that PN basal dendrites possess significant analog computing capabilities, and suggest that the diverse forms of nonlinear response modulation seen in the neocortex, including uni-modal, cross-modal, and attentional effects, could depend in part on pathway-specific biases in the spatial distribution of excitatory synaptic contacts onto PN basal dendritic arbors.

  2. Dendritic cell reprogramming by the hypoxic environment.

    Science.gov (United States)

    Bosco, Maria Carla; Varesio, Luigi

    2012-12-01

    Myeloid dendritic cells (DCs) are professional antigen-presenting cells central to the orchestration of innate and acquired immunity and the maintenance of self-tolerance. The local microenvironment contributes to the regulation of DC development and functions, and deregulated DC responses may result in amplification of inflammation, loss of tolerance, or establishment of immune escape mechanisms. DC generation from monocytic precursors recruited at sites of inflammation, tissue damage, or neoplasia occurs under condition of low partial oxygen pressure (pO(2), hypoxia). We reviewed the literature addressing the phenotypic and functional changes triggered by hypoxia in monocyte-derived immature (i) and mature (m) DCs. The discussion will revolve around in vitro studies of gene expression profile, which give a comprehensive representation of the complexity of response of these cells to low pO(2). The gene expression pattern of hypoxic DC will be discussed to address the question of the relationship with a specific maturation stage. We will summarize data relative to the regulation of the chemotactic network, which points to a role for hypoxia in promoting a migratory phenotype in iDCs and a highly proinflammatory state in mDCs. Current knowledge of the strict regulatory control exerted by hypoxia on the expression of immune-related cell surface receptors will also be addressed, with a particular focus on a newly identified marker of hypoxic DCs endowed with proinflammatory properties. Furthermore, we discuss the literature on the transcription mechanisms underlying hypoxia-regulated gene expression in DCs, which support a major role for the HIF/HRE pathway. Finally, recent advances shedding light on the in vivo influence of the local hypoxic microenvironment on DCs infiltrating the inflamed joints of juvenile idiopathic arthritis patients are outlined. PMID:22901977

  3. Glucocorticoid receptor translational isoforms underlie maturational stage-specific glucocorticoid sensitivities of dendritic cells in mice and humans

    OpenAIRE

    Cao, Yun; Bender, Ingrid K.; Konstantinidis, Athanasios K.; Shin, Soon Cheon; Jewell, Christine M.; Cidlowski, John A; Schleimer, Robert P.; Lu, Nick Z.

    2013-01-01

    Mature, but not immature, dendritic cells are sensitive to glucocorticoid-induced apoptosis.Mature, but not immature, dendritic cells express proapoptotic glucocorticoid receptor translational isoforms.

  4. Tau causes synapse loss without disrupting calcium homeostasis in the rTg4510 model of tauopathy.

    Directory of Open Access Journals (Sweden)

    Katherine J Kopeikina

    Full Text Available Neurofibrillary tangles (NFTs of tau are one of the defining hallmarks of Alzheimer's disease (AD, and are closely associated with neuronal degeneration. Although it has been suggested that calcium dysregulation is important to AD pathogenesis, few studies have probed the link between calcium homeostasis, synapse loss and pathological changes in tau. Here we test the hypothesis that pathological changes in tau are associated with changes in calcium by utilizing in vivo calcium imaging in adult rTg4510 mice that exhibit severe tau pathology due to over-expression of human mutant P301L tau. We observe prominent dendritic spine loss without disruptions in calcium homeostasis, indicating that tangles do not disrupt this fundamental feature of neuronal health, and that tau likely induces spine loss in a calcium-independent manner.

  5. The dendritic density field of a cortical pyramidal cell

    Directory of Open Access Journals (Sweden)

    Hermann eCuntz

    2012-02-01

    Full Text Available Much is known about the computation in individual neurons in the cortical column. Also, the selective connectivity between many cortical neuron types has been studied in great detail. But due to the complexity of this microcircuitry its functional role within the cortical column remains a mystery. Some of the wiring behavior between neurons can be interpreted directly from their particular dendritic and axonal shapes. Here, I describe the dendritic density field as one key element that remains to be better understood. I sketch an approach to relate dendritic density fields in general to their underlying potential connectivity schemes. As an example, I show how the characteristic shape of a cortical pyramidal cell appears as a direct consequence of connecting inputs arranged in two separate parallel layers.

  6. Robust Type-specific Hemisynapses Induced by Artificial Dendrites

    Science.gov (United States)

    Kim, Eun Joong; Jeon, Chang Su; Lee, Soo Youn; Hwang, Inseong; Chung, Taek Dong

    2016-04-01

    Type-specificity of synapses, excitatory and inhibitory, regulates information process in neural networks via chemical neurotransmitters. To lay a foundation of synapse-based neural interfaces, artificial dendrites are generated by covering abiotic substrata with ectodomains of type-specific synaptogenic proteins that are C-terminally tagged with biotinylated fluorescent proteins. The excitatory artificial synapses displaying engineered ectodomains of postsynaptic neuroligin-1 (NL1) induce the formation of excitatory presynapses with mixed culture of neurons in various developmental stages, while the inhibitory artificial dendrites displaying engineered NL2 and Slitrk3 induce inhibitory presynapses only with mature neurons. By contrast, if the artificial dendrites are applied to the axonal components of micropatterned neurons, correctly-matched synaptic specificity emerges regardless of the neuronal developmental stages. The hemisynapses retain their initially established type-specificity during neuronal development and maintain their synaptic strength provided live neurons, implying the possibility of durable synapse-based biointerfaces.

  7. MicroRNA-9 controls dendritic development by targeting REST

    Science.gov (United States)

    Giusti, Sebastian A; Vogl, Annette M; Brockmann, Marisa M; Vercelli, Claudia A; Rein, Martin L; Trümbach, Dietrich; Wurst, Wolfgang; Cazalla, Demian; Stein, Valentin; Deussing, Jan M; Refojo, Damian

    2014-01-01

    MicroRNAs (miRNAs) are conserved noncoding RNAs that function as posttranscriptional regulators of gene expression. miR-9 is one of the most abundant miRNAs in the brain. Although the function of miR-9 has been well characterized in neural progenitors, its role in dendritic and synaptic development remains largely unknown. In order to target miR-9 in vivo, we developed a transgenic miRNA sponge mouse line allowing conditional inactivation of the miR-9 family in a spatio-temporal-controlled manner. Using this novel approach, we found that miR-9 controls dendritic growth and synaptic transmission in vivo. Furthermore, we demonstrate that miR-9-mediated downregulation of the transcriptional repressor REST is essential for proper dendritic growth. DOI: http://dx.doi.org/10.7554/eLife.02755.001 PMID:25406064

  8. Involvement of dendritic cells in autoimmune diseases in children

    Directory of Open Access Journals (Sweden)

    Reed Ann M

    2007-07-01

    Full Text Available Abstract Dendritic cells (DCs are professional antigen-presenting cells that are specialized in the uptake of antigens and their transport from peripheral tissues to the lymphoid organs. Over the last decades, the properties of DCs have been intensely studied and much knowledge has been gained about the role of DCs in various diseases and health conditions where the immune system is involved, particularly in cancer and autoimmune disorders. Emerging clues in autoimmune diseases, suggest that dendritic cell dysregulation might be involved in the development of various autoimmune disorders in both adults and children. However, studies investigating a possible contribution of DCs in autoimmune diseases in the pediatric population alone are scanty. The purpose of this review is to give a general overview of the current literature on the relevance of dendritic cells in the most common autoimmune conditions of childhood.

  9. A Model of Dendritic Cell Therapy for Melanoma

    Directory of Open Access Journals (Sweden)

    Ami eRadunskaya

    2013-03-01

    Full Text Available Dendritic cells are a promising immunotherapy tool for boosting an individual's antigen specific immune response to cancer. We develop a mathematical model using differential and delay-differential equations to describe the interactions between dendritic cells, effector-immune cells and tumor cells. We account for the trafficking of immune cells between lymph, blood, and tumor compartments. Our model reflects experimental results both for dendritic-cell trafficking and for immune suppression of tumor growth in mice. In addition, in silico experiments suggest more effective immunotherapy treatment protocols can be achieved by modifying dose location and schedule. A sensitivity analysis of the model reveals which patient-specific parameters have the greatest impact on treatment efficacy.

  10. Survey of disruption causes at JET

    NARCIS (Netherlands)

    de Vries, P. C.; Johnson, M. F.; Alper, B.; Buratti, P.; Hender, T. C.; Koslowski, H. R.; Riccardo, V.

    2011-01-01

    A survey has been carried out into the causes of all 2309 disruptions over the last decade of JET operations. The aim of this survey was to obtain a complete picture of all possible disruption causes, in order to devise better strategies to prevent or mitigate their impact. The analysis allows the e

  11. Rurality and Patterns of Social Disruption.

    Science.gov (United States)

    Wilkinson, Kenneth P.

    1984-01-01

    Argues that structural cleavages provoke social disruptions where opportunities are conducive. Thus, combinations of rurality with particular structural cleavages predict specific disruption patterns. Data from northeastern United States indicate that rurality, combined with other population characteristics (provocation, ascriptive inequality,…

  12. Network Formation under the Threat of Disruption

    NARCIS (Netherlands)

    Hoyer, B.

    2013-01-01

    The studies in this thesis are focused on the impact the presence of a network disruptor has on network formation models. In particular, we build two theoretical models to study the effect of network disruption on network formation and test the effect network disruption has on equilibrium selection

  13. Blastic plasmacytoid dendritic cell neoplasm with absolute monocytosis at presentation

    Directory of Open Access Journals (Sweden)

    Jaworski JM

    2015-02-01

    Full Text Available Joseph M Jaworski,1,2 Vanlila K Swami,1 Rebecca C Heintzelman,1 Carrie A Cusack,3 Christina L Chung,3 Jeremy Peck,3 Matthew Fanelli,3 Micheal Styler,4 Sanaa Rizk,4 J Steve Hou1 1Department of Pathology and Laboratory Medicine, Hahnemann University Hospital/Drexel University College of Medicine, Philadelphia, PA, USA; 2Department of Pathology, Mercy Fitzgerald Hospital, Darby, PA, USA; 3Department of Dermatology, Hahnemann University Hospital/Drexel University College of Medicine, Philadelphia, PA, USA; 4Department of Hematology/Oncology, Hahnemann University Hospital/Drexel University College of Medicine, Philadelphia, PA, USA Abstract: Blastic plasmacytoid dendritic cell neoplasm is an uncommon malignancy derived from precursors of plasmacytoid dendritic cells. Nearly all patients present initially with cutaneous manifestations, with many having extracutaneous disease additionally. While response to chemotherapy initially is effective, relapse occurs in most, with a leukemic phase ultimately developing. The prognosis is dismal. While most of the clinical and pathologic features are well described, the association and possible prognostic significance between peripheral blood absolute monocytosis (>1.0 K/µL and blastic plasmacytoid dendritic cell neoplasm have not been reported. We report a case of a 68-year-old man who presented with a rash for 4–5 months. On physical examination, there were multiple, dull-pink, indurated plaques on the trunk and extremities. Complete blood count revealed thrombocytopenia, absolute monocytosis of 1.7 K/µL, and a negative flow cytometry study. Biopsy of an abdominal lesion revealed typical features of blastic plasmacytoid dendritic cell neoplasm. Patients having both hematologic and nonhematologic malignancies have an increased incidence of absolute monocytosis. Recent studies examining Hodgkin and non-Hodgkin lymphoma patients have suggested that this is a negative prognostic factor. The association between

  14. Facile fabrication of dendritic silver structures and their surface enhanced Raman spectroscopic properties

    Indian Academy of Sciences (India)

    Jisheng Yang; Zhengdong Jiang

    2015-01-01

    A simple and efficient approach was developed to fabricate silver dendrites by Cu reducing Ag+ in AgNO3 solution. The growth speed, morphologies and structures of the silver dendrites strongly depend on AgNO3 concentration and reaction time. The silver dendrites were formed from nanosheets and the crystal structure is face-centered cubic. Rhodamine 6G was used as probe molecule to show that the silver dendrites have high sensitivity to surface enhanced Raman spectroscopy response.

  15. Age-related dendritic hypertrophy and sexual dimorphism in rat basolateral amygdala

    OpenAIRE

    Rubinow, Marisa J.; Drogos, Lauren L.; Juraska, Janice M.

    2007-01-01

    Little research has examined the influence of aging or sex on anatomical measures in the basolateral amygdala. We quantified spine density and dendritic material in Golgi-Cox stained tissue of the basolateral nucleus in young adult (3–5 months) and aged (20–24 months) male and female Long-Evans rats. Dendritic branching and spine density were measured in principal neurons. Age, but not sex, influenced the dendritic tree, with aged animals displaying significantly more dendritic material. Prev...

  16. Long-term depression is differentially expressed in distinct lamina of hippocampal CA1 dendrites

    Directory of Open Access Journals (Sweden)

    Binu eRamachandran

    2015-02-01

    Full Text Available Information storage in CA1 hippocampal pyramidal neurons is compartmentalized in proximal versus distal apical dendrites, cell bodies, and basal dendrites. This compartmentalization is thought to be essential for synaptic integration. Differences in the expression of LTP in each of these compartments have been described, but less is known regarding potential differences in LTD. Here, to directly compare LTD expression in each compartment and to bypass possible differences in input-specificity and stimulation of presynaptic inputs, we used global application of NMDA to induce LTD. We then examined LTD expression in each dendritic sub-region - proximal and distal apical, and basal dendrites - and in cell bodies. Interestingly, we found that distal apical dendrites exhibited the greatest magnitude of LTD of all areas tested and this LTD was maintained, whereas LTD in proximal apical dendrites was not maintained. In basal dendrites, LTD was also maintained, but the magnitude of LTD was less than in distal apical dendrites. Blockade of inhibition blocked LTD maintenance in both distal apical and basal dendrites. Population spikes recorded from the cell body layer correlated with apical dendrite fEPSPs, where LTD was maintained in distal dendrites and decayed in proximal dendrites. On the other hand, LTD of basal dendrite fEPSPs was maintained but population spike responses were not. Thus E-S coupling was distinct in basal and apical dendrites. Our data demonstrate cell autonomous differential information processing in somas and dendritic sub-regions of CA1 pyramidal neurons in the hippocampus, where LTD expression is intrinsic to distinct dendritic regions, and does not depend on the nature of stimulation and input specificity.

  17. Characteristic Parameters for Dendritic Microstructure of Solidification During Slab Continuous Casting

    Institute of Scientific and Technical Information of China (English)

    GUO Wei; ZHU Miao-yong

    2009-01-01

    The operating conditions during the continuous casting process have a great effect on the microstructure of slab solidification,including primary and secondary dendritic arm spacing.On the basis of the analysis of available work,a revised expression for describing secondary dendritic arm spacing during solidification of slab continuous casting was presented,and the relation between the ratio of primary dendritic arm spacing to secondary dendritic arm spacing and the cooling rate was obtained.

  18. Dendritic Heterojunction Nanowire Arrays for High-Performance Supercapacitors

    OpenAIRE

    Rujia Zou; Zhenyu Zhang; Muk Fung Yuen; Junqing Hu; Chun-Sing Lee; Wenjun Zhang

    2015-01-01

    Herein, we designed and synthesized for the first time a series of 3D dendritic heterojunction arrays on Ni foam substrates, with NiCo2S4 nanowires as cores and NiCo2O4, NiO, Co3O4, and MnO2 nanowires as branches, and studied systematically their electrochemical performance in comparison with their counterparts in core/shell structure. Attributed to the following reasons: (1) both core and branch are pseudocapacitively active materials, (2) the special dendritic structure with considerable in...

  19. Macrophages as APC and the dendritic cell myth.

    Science.gov (United States)

    Hume, David A

    2008-11-01

    Dendritic cells have been considered an immune cell type that is specialized for the presentation of Ag to naive T cells. Considerable effort has been applied to separate their lineage, pathways of differentiation, and effectiveness in Ag presentation from those of macrophages. This review summarizes evidence that dendritic cells are a part of the mononuclear phagocyte system and are derived from a common precursor, responsive to the same growth factors (including CSF-1), express the same surface markers (including CD11c), and have no unique adaptation for Ag presentation that is not shared by other macrophages.

  20. Modelling dendritic ecological networks in space: anintegrated network perspective

    Science.gov (United States)

    Peterson, Erin E.; Ver Hoef, Jay M.; Isaak, Dan J.; Falke, Jeffrey A.; Fortin, Marie-Josée; Jordon, Chris E.; McNyset, Kristina; Monestiez, Pascal; Ruesch, Aaron S.; Sengupta, Aritra; Som, Nicholas; Steel, E. Ashley; Theobald, David M.; Torgersen, Christian E.; Wenger, Seth J.

    2013-01-01

    Dendritic ecological networks (DENs) are a unique form of ecological networks that exhibit a dendritic network topology (e.g. stream and cave networks or plant architecture). DENs have a dual spatial representation; as points within the network and as points in geographical space. Consequently, some analytical methods used to quantify relationships in other types of ecological networks, or in 2-D space, may be inadequate for studying the influence of structure and connectivity on ecological processes within DENs. We propose a conceptual taxonomy of network analysis methods that account for DEN characteristics to varying degrees and provide a synthesis of the different approaches within

  1. Ternary eutectic dendrites: Pattern formation and scaling properties

    OpenAIRE

    Rátkai, László; Szállás, Attila; Pusztai, Tamás; Mohri, Tetsuo; Gránásy, László

    2015-01-01

    Extending previous work [T. Pusztai, L. R\\'atkai, A. Sz\\'all\\'as, and L. Gr\\'an\\'asy, Phys. Rev. E {\\bf 87}, 032402 (2013)], we have studied the formation of eutectic dendrites in a model ternary system within the framework of the phase-field theory. We have mapped out the domain in which two-phase dendritic structures grow. With increasing pulling velocity, the following sequence of growth morphologies is observed: flat front lamellae $\\rightarrow$ eutectic colonies $\\rightarrow$ eutectic de...

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  18. Multivalent glycopeptide dendrimers for the targeted delivery of antigens to dendritic cells

    NARCIS (Netherlands)

    J.J. García-Vallejo; M. Ambrosini; A. Overbeek; W.E. van Riel; K. Bloem; W.W.J. Unger; F. Chiodo; J.G. Bolscher; K. Nazmi; H. Kalay; Y. van Kooyk

    2013-01-01

    Dendritic cells are the most powerful type of antigen presenting cells. Current immunotherapies targeting dendritic cells have shown a relative degree of success but still require further improvement. One of the most important issues to solve is the efficiency of antigen delivery to dendritic cells

  19. Cellular source-specific effects of apolipoprotein (apo E4 on dendrite arborization and dendritic spine development.

    Directory of Open Access Journals (Sweden)

    Sachi Jain

    Full Text Available Apolipoprotein (apo E4 is the leading genetic risk factor for Alzheimer's disease (AD, and it has a gene dose-dependent effect on the risk and age of onset of AD. Although apoE4 is primarily produced by astrocytes in the brain, neurons can also produce apoE4 under stress conditions. ApoE4 is known to inhibit neurite outgrowth and spine development in vitro and in vivo, but the potential influence of apoE4's cellular source on dendritic arborization and spine development has not yet been investigated. In this study, we report impairments in dendritic arborization and a loss of spines, especially thin (learning and mushroom (memory spines, in the hippocampus and entorhinal cortex of 19-21-month-old female neuron-specific-enolase (NSE-apoE4 and apoE4-knockin (KI mice compared to their respective apoE3-expressing counterparts. In general, NSE-apoE4 mice had more severe and widespread deficits in dendritic arborization as well as spine density and morphology than apoE4-KI mice. The loss of dendritic spines, especially mushroom spines, occurred in NSE-apoE4 mice as early as 7-8 months of age. In contrast, glial fibrillary acidic protein (GFAP-apoE4 mice, which express apoE4 solely in astrocytes, did not have impairments in their dendrite arborization or spine density and morphology compared to GFAP-apoE3 mice at both ages. These results indicate that the effects of apoE4 on dendrite arborization, spine density, and spine morphology depend critically on its cellular source, with neuronal apoE4 having more detrimental effects than astrocytic apoE4.

  20. Cellular source-specific effects of apolipoprotein (apo) E4 on dendrite arborization and dendritic spine development.

    Science.gov (United States)

    Jain, Sachi; Yoon, Seo Yeon; Leung, Laura; Knoferle, Johanna; Huang, Yadong

    2013-01-01

    Apolipoprotein (apo) E4 is the leading genetic risk factor for Alzheimer's disease (AD), and it has a gene dose-dependent effect on the risk and age of onset of AD. Although apoE4 is primarily produced by astrocytes in the brain, neurons can also produce apoE4 under stress conditions. ApoE4 is known to inhibit neurite outgrowth and spine development in vitro and in vivo, but the potential influence of apoE4's cellular source on dendritic arborization and spine development has not yet been investigated. In this study, we report impairments in dendritic arborization and a loss of spines, especially thin (learning) and mushroom (memory) spines, in the hippocampus and entorhinal cortex of 19-21-month-old female neuron-specific-enolase (NSE)-apoE4 and apoE4-knockin (KI) mice compared to their respective apoE3-expressing counterparts. In general, NSE-apoE4 mice had more severe and widespread deficits in dendritic arborization as well as spine density and morphology than apoE4-KI mice. The loss of dendritic spines, especially mushroom spines, occurred in NSE-apoE4 mice as early as 7-8 months of age. In contrast, glial fibrillary acidic protein (GFAP)-apoE4 mice, which express apoE4 solely in astrocytes, did not have impairments in their dendrite arborization or spine density and morphology compared to GFAP-apoE3 mice at both ages. These results indicate that the effects of apoE4 on dendrite arborization, spine density, and spine morphology depend critically on its cellular source, with neuronal apoE4 having more detrimental effects than astrocytic apoE4.

  1. The role of ongoing dendritic oscillations in single-neuron dynamics.

    Science.gov (United States)

    Remme, Michiel W H; Lengyel, Máté; Gutkin, Boris S

    2009-09-01

    The dendritic tree contributes significantly to the elementary computations a neuron performs while converting its synaptic inputs into action potential output. Traditionally, these computations have been characterized as both temporally and spatially localized. Under this localist account, neurons compute near-instantaneous mappings from their current input to their current output, brought about by somatic summation of dendritic contributions that are generated in functionally segregated compartments. However, recent evidence about the presence of oscillations in dendrites suggests a qualitatively different mode of operation: the instantaneous phase of such oscillations can depend on a long history of inputs, and under appropriate conditions, even dendritic oscillators that are remote may interact through synchronization. Here, we develop a mathematical framework to analyze the interactions of local dendritic oscillations and the way these interactions influence single cell computations. Combining weakly coupled oscillator methods with cable theoretic arguments, we derive phase-locking states for multiple oscillating dendritic compartments. We characterize how the phase-locking properties depend on key parameters of the oscillating dendrite: the electrotonic properties of the (active) dendritic segment, and the intrinsic properties of the dendritic oscillators. As a direct consequence, we show how input to the dendrites can modulate phase-locking behavior and hence global dendritic coherence. In turn, dendritic coherence is able to gate the integration and propagation of synaptic signals to the soma, ultimately leading to an effective control of somatic spike generation. Our results suggest that dendritic oscillations enable the dendritic tree to operate on more global temporal and spatial scales than previously thought; notably that local dendritic activity may be a mechanism for generating on-going whole-cell voltage oscillations. PMID:19730677

  2. Erosion products in disruption simulation experiments

    Energy Technology Data Exchange (ETDEWEB)

    Safronov, V.; Arkhipov, N.; Bakhtin, V.; Barsuk, V.; Kurkin, S.; Mironova, E.; Toporkov, D.; Vasenin, S.; Zhitlukhin, A. [Troitsk Inst. for Innovation and Fusion Research, Troisk, Moscow region (Russian Federation); Arkhipov, I. [Inst. of Physical Chemistry, Russian Academy of Science, Moscow (Russian Federation); Werle, H.; Wuerz, H. [Forschungszentrum Karlsruhe (Germany)

    1998-07-01

    Erosion of divertor materials under tokamak disruption event presents a serious problem of ITER technology. Erosion restricts the divertor lifetime and leads to production of redeposited layers of the material retaining large amount of tritium, which is a major safety issue for future fusion reactor. Since ITER disruptive heatloads are not achievable in existing tokamaks, material erosion is studied in special simulation experiments. Till now the simulation experiments have focused mainly on investigation of shielding effect and measurement of erosion rate. In the present work the properties of eroded and redeposited graphite are studied under condition typical for hard ITER disruption. (author)

  3. Disruptive School Peers and Student Outcomes

    DEFF Research Database (Denmark)

    Kristoffersen, Jannie H. G.; Krægpøth, Morten Visby; Skyt Nielsen, Helena;

    This paper estimates how peers’ achievement gains are affected by the presence of potentially disruptive and emotionally sensitive children in the school-cohort. We exploit that some children move between schools and thus generate variation in peer composition in the receiving schoolcohort. We...... identify three groups of potentially disruptive and emotionally sensitive children from detailed Danish register data: children with divorced parents, children with parents convicted of crime, and children with a psychiatric diagnosis. We find that adding potentially disruptive children lowers the academic...... achievement of peers by about 1.5-2 percent of a standard deviation....

  4. Disruptive School Peers and Student Outcomes

    DEFF Research Database (Denmark)

    Kristoffersen, Jannie H. Grøne; Krægpøth, Morten; Nielsen, Helena Skyt;

    This paper estimates how peers’ achievement gains are affected by the presence of potentially disruptive and emotionally sensitive children in the school-cohort. We exploit that some children move between schools and thus generate variation in peer composition in the receiving school-cohort. We...... identify three groups of potentially disruptive and emotionally sensitive children from detailed Danish register data: children with divorced parents, children with parents convicted of crime, and children with a psychiatric diagnosis. We find that adding potentially disruptive children lowers the academic...... achievement of peers by about 1.7-2.3 percent of a standard deviation....

  5. Disruptive School Peers and Student Outcomes

    DEFF Research Database (Denmark)

    Kristoffersen, Jannie H. G.; Krægpøth, Morten; Nielsen, Helena Skyt;

    2015-01-01

    This paper estimates how peers’ achievement gains are affected by the presence of potentially disruptive and emotionally sensitive children in the school-cohort. We exploit that some children move between schools and thus generate variation in peer composition in the receiving school-cohort. We...... identify three groups of potentially disruptive and emotionally sensitive children from detailed Danish register data: children with divorced parents, children with parents convicted of crime, and children with a psychiatric diagnosis. We find that adding potentially disruptive children lowers the academic...... achievement of peers by about 1.7–2.3% of a standard deviation....

  6. OF SYSTEMS THAT HAVE DISRUPTABLE CONSTRAINS

    Directory of Open Access Journals (Sweden)

    Chernov Yuriy Tikhonovich

    2012-07-01

    Formulas of equivalent static loads, with the help of which the systems are analyzed when constraints are disrupted, are generated. No inertial force is to be derived to obtain equivalent static loads. This is important in view of their application in dynamic analyses . Analysis of the static system in the event of disrupted constraints is based on the equations derived by the authors. The result of the analysis represents an inverse linear relation of static loading and relative stiffness of the system with disrupted constraints. This means that the lower the stiffness of the system, the higher the static loading.

  7. Disruption Management in Passenger Railway Transportation

    DEFF Research Database (Denmark)

    Groth, Julie Jespersen; Potthoff, Daniel; Clausen, Jens;

    2009-01-01

    This paper deals with disruption management in passenger railway transportation. In the disruption management process, many actors belonging to different organizations play a role. In this paper we therefore describe the process itself and the roles of the different actors. Furthermore, we discuss...... the three main subproblems in railway disruption management: timetable adjustment, and rolling stock and crew re-scheduling. Next to a general description of these problems, we give an overview of the existing literature and we present some details of the specific situations at DSB S-tog and NS...

  8. DISRUPTIVE BEHAVIOUR AMONGST DOCTORS, MYTH OR REALITY?

    Directory of Open Access Journals (Sweden)

    Avtar Singh

    2014-01-01

    Full Text Available BACKGROUND : Disruptive behavior in a medical setting is defined as objectionable or offensive interpersonal behavior that leads to disruption of professional activities in the workplace. 1 It has been observed that majority of doctors do not show disruptive behavior in their day today conduct and only few doctors are identified for their disruptive behavior . Special commi ttee on professional conduct and ethics defines disruptive behavior in physicians as aberrant behavior manifested through personal interaction with physicians , hospital personnel , health care professionals , patients , family members or others which interferes with patient care or could reasonably be expected to interfere with the process of delivering quality care. 2 Common forms of disruptive behaviors generally seen amongst young doctors are use of abusive language , yelling or shouting at patients , colleagues and subordinate staff , showing in disciplined behavior and at times indulging in physical abuse. 3 - 4 STUDY DESIGN : Study was conducted at a tertiary care hospital where 614 health care professionals participated which included 108 doctors 432 nurs ing staff and 74 paramedical staff METHOD : Data collection was done by semi structured pretested questionnaire and was entered in Microsoft Excel and analyzed for frequency and percentages . RESULTS : 64 % doctor , 66% nursing staff and 50% of the paramedicals answered that they have seen doctors showing disruptive behavior at one time or the other . Not all the doctors show disruptive behavior but this type of aberrant behavior is seen mainly in2 - 3 percent of doctors only. While answering to the que stion as to the type of disruptive behavior , 57% health care professionals reported that commonest form of disruptive behavior noticed by them amongst doctors was yelling or shouting on junior staff , patients and colleagues . 47% answered that doctors with disruptive behavior do not follow laid down orders or

  9. Clinical application of dendritic cells in cancer vaccination therapy

    DEFF Research Database (Denmark)

    Svane, Inge Marie; Soot, Mette Line; Buus, Søren;

    2003-01-01

    for large-scale generation of dendritic cells for clinical applications has made possible phase I/II studies designed to analyze the toxicity, feasibility and efficacy of this approach. In clinical trials, DC-based vaccination of patients with advanced cancer has in many cases led to immunity...

  10. Kicking off adaptive immunity: the discovery of dendritic cells

    OpenAIRE

    Katsnelson, Alla

    2006-01-01

    In 1973, Ralph Steinman and Zanvil Cohn discovered an unusual looking population of cells with an unprecedented ability to activate naive T cells. Dubbed “dendritic cells,” these cells are now known as the primary instigators of adaptive immunity.

  11. Lithium dendrite growth through solid polymer electrolyte membranes

    Science.gov (United States)

    Harry, Katherine; Schauser, Nicole; Balsara, Nitash

    2015-03-01

    Replacing the graphite-based anode in current batteries with a lithium foil will result in a qualitative increase in the energy density of lithium batteries. The primary reason for not adopting lithium-foil anodes is the formation of dendrites during cell charging. In this study, stop-motion X-ray microtomography experiments were used to directly monitor the growth of lithium dendrites during electrochemical cycling of symmetric lithium-lithium cells with a block copolymer electrolyte. In an attempt to understand the relationship between viscoelastic properties of the electrolyte on dendrite formation, a series of complementary experiments including cell cycling, tomography, ac impedance, and rheology, were conducted above and below the glass transition temperature of the non-conducting poly(styrene) block; the conducting phase is a mixture of rubbery poly(ethylene oxide) and a lithium salt. The tomography experiments enable quantification of the evolution of strain in the block copolymer electrolyte. Our work provides fundamental insight into the dynamics of electrochemical deposition of metallic films in contact with high modulus polymer electrolytes. Rational approaches for slowing down and, perhaps, eliminating dendrite growth are proposed.

  12. Dynamic microtubules regulate dendritic spine morphology and synaptic plasticity

    NARCIS (Netherlands)

    J. Jaworski; L.C. Kapitein; S. Montenegro Gouveia; B.R. Dortland; P.S. Wulf; I. Grigoriev; P. Camera; S.A. Spangler; P. Di Stefano; J. Demmers; H. Krugers; P. Defilippi; A. Akhmanova; C.C. Hoogenraad

    2009-01-01

    Dendritic spines are the major sites of excitatory synaptic input, and their morphological changes have been linked to learning and memory processes. Here, we report that growing microtubule plus ends decorated by the microtubule tip-tracking protein EB3 enter spines and can modulate spine morpholog

  13. Synaptic integration in dendrites: exceptional need for speed.

    Science.gov (United States)

    Golding, Nace L; Oertel, Donata

    2012-11-15

    Some neurons in the mammalian auditory system are able to detect and report the coincident firing of inputs with remarkable temporal precision. A strong, low-voltage-activated potassium conductance (g(KL)) at the cell body and dendrites gives these neurons sensitivity to the rate of depolarization by EPSPs, allowing neurons to assess the coincidence of the rising slopes of unitary EPSPs. Two groups of neurons in the brain stem, octopus cells in the posteroventral cochlear nucleus and principal cells of the medial superior olive (MSO), extract acoustic information by assessing coincident firing of their inputs over a submillisecond timescale and convey that information at rates of up to 1000 spikes s(-1). Octopus cells detect the coincident activation of groups of auditory nerve fibres by broadband transient sounds, compensating for the travelling wave delay by dendritic filtering, while MSO neurons detect coincident activation of similarly tuned neurons from each of the two ears through separate dendritic tufts. Each makes use of filtering that is introduced by the spatial distribution of inputs on dendrites. PMID:22930273

  14. Plasmacytoid dendritic cells migrate in afferent skin lymph.

    Science.gov (United States)

    Pascale, Florentina; Pascale, Florentia; Contreras, Vanessa; Bonneau, Michel; Courbet, Alexandre; Chilmonczyk, Stefan; Bevilacqua, Claudia; Epardaud, Mathieu; Eparaud, Mathieu; Niborski, Violeta; Riffault, Sabine; Balazuc, Anne-Marie; Foulon, Eliane; Guzylack-Piriou, Laurence; Riteau, Beatrice; Hope, Jayne; Bertho, Nicolas; Charley, Bernard; Schwartz-Cornil, Isabelle

    2008-05-01

    Conventional dendritic cells enter lymph nodes by migrating from peripheral tissues via the lymphatic route, whereas plasmacytoid dendritic cells (pDC), also called IFN-producing cells (IPC), are described to gain nodes from blood via the high endothelial venules. We demonstrate here that IPC/pDC migrate in the afferent lymph of two large mammals. In sheep, injection of type A CpG oligodinucleotide (ODN) induced lymph cells to produce type I IFN. Furthermore, low-density lymph cells collected at steady state produced type I IFN after stimulation with type A CpG ODN and enveloped viruses. Sheep lymph IPC were found within a minor B(neg)CD11c(neg) subset expressing CD45RB. They presented a plasmacytoid morphology, expressed high levels of TLR-7, TLR-9, and IFN regulatory factor 7 mRNA, induced IFN-gamma production in allogeneic CD4(pos) T cells, and differentiated into dendritic cell-like cells under viral stimulation, thus fulfilling criteria of bona fide pDC. In mini-pig, a CD4(pos)SIRP(pos) subset in afferent lymph cells, corresponding to pDC homologs, produced type I IFN after type A CpG-ODN triggering. Thus, pDC can link innate and acquired immunity by migrating from tissue to draining node via lymph, similarly to conventional dendritic cells. PMID:18424716

  15. Multimodal imaging of nanovaccine carriers targeted to human dendritic cells

    NARCIS (Netherlands)

    Cruz, L.J.; Tacken, P.J.; Bonetto, F.J.; Buschow, S.I.; Croes, H.J.E.; Wijers-Rouw, M.J.P.; Vries, I.J.M. de; Figdor, C.G.

    2011-01-01

    Dendritic cells (DCs) are key players in the initiation of adaptive immune responses and are currently exploited in immunotherapy against cancer and infectious diseases. The targeted delivery of nanovaccine particles (NPs) to DCs in vivo is a promising strategy to enhance immune responses. Here, tar

  16. Dendritic cell-tumor cell hybrids and immunotherapy

    DEFF Research Database (Denmark)

    Cathelin, Dominique; Nicolas, Alexandra; Bouchot, André;

    2011-01-01

    Dendritic cells (DC) are professional antigen-presenting cells currently being used as a cellular adjuvant in cancer immunotherapy strategies. Unfortunately, DC-based vaccines have not demonstrated spectacular clinical results. DC loading with tumor antigens and DC differentiation and activation...

  17. Dendritic Spines in Depression: What We Learned from Animal Models

    Directory of Open Access Journals (Sweden)

    Hui Qiao

    2016-01-01

    Full Text Available Depression, a severe psychiatric disorder, has been studied for decades, but the underlying mechanisms still remain largely unknown. Depression is closely associated with alterations in dendritic spine morphology and spine density. Therefore, understanding dendritic spines is vital for uncovering the mechanisms underlying depression. Several chronic stress models, including chronic restraint stress (CRS, chronic unpredictable mild stress (CUMS, and chronic social defeat stress (CSDS, have been used to recapitulate depression-like behaviors in rodents and study the underlying mechanisms. In comparison with CRS, CUMS overcomes the stress habituation and has been widely used to model depression-like behaviors. CSDS is one of the most frequently used models for depression, but it is limited to the study of male mice. Generally, chronic stress causes dendritic atrophy and spine loss in the neurons of the hippocampus and prefrontal cortex. Meanwhile, neurons of the amygdala and nucleus accumbens exhibit an increase in spine density. These alterations induced by chronic stress are often accompanied by depression-like behaviors. However, the underlying mechanisms are poorly understood. This review summarizes our current understanding of the chronic stress-induced remodeling of dendritic spines in the hippocampus, prefrontal cortex, orbitofrontal cortex, amygdala, and nucleus accumbens and also discusses the putative underlying mechanisms.

  18. Role of plasmacytoid dendritic cells in breast cancer bone dissemination

    OpenAIRE

    Sawant, Anandi; Ponnazhagan, Selvarangan

    2013-01-01

    Elevated levels of plasmacytoid dendritic cells (pDC) have been observed as breast cancer disseminates to the bone. The selective depletion of pDC in mice led to a total abrogation of bone metastasis as well as to an increase in TH1 antitumor response, suggesting that pDC may be considered as a potential therapeutic target for metastatic breast cancer.

  19. Avian dendritic cells: Phenotype and ontogeny in lymphoid organs.

    Science.gov (United States)

    Nagy, Nándor; Bódi, Ildikó; Oláh, Imre

    2016-05-01

    Dendritic cells (DC) are critically important accessory cells in the innate and adaptive immune systems. Avian DCs were originally identified in primary and secondary lymphoid organs by their typical morphology, displaying long cell processes with cytoplasmic granules. Several subtypes are known. Bursal secretory dendritic cells (BSDC) are elongated cells which express vimentin intermediate filaments, MHC II molecules, macrophage colony-stimulating factor 1 receptor (CSF1R), and produce 74.3+ secretory granules. Avian follicular dendritic cells (FDC) highly resemble BSDC, express the CD83, 74.3 and CSF1R molecules, and present antigen in germinal centers. Thymic dendritic cells (TDC), which express 74.3 and CD83, are concentrated in thymic medulla while interdigitating DC are found in T cell-rich areas of secondary lymphoid organs. Avian Langerhans cells are a specialized 74.3-/MHC II+ cell population found in stratified squamous epithelium and are capable of differentiating into 74.3+ migratory DCs. During organogenesis hematopoietic precursors of DC colonize the developing lymphoid organ primordia prior to immigration of lymphoid precursor cells. This review summarizes our current understanding of the ontogeny, cytoarchitecture, and immunophenotype of avian DC, and offers an antibody panel for the in vitro and in vivo identification of these heterogeneous cell types.

  20. Principles of self-assembly of helical pores from dendritic dipeptides

    OpenAIRE

    Percec, Virgil; Dulcey, Andrés E.; Peterca, Mihai; Ilies, Monica; Nummelin, Sami; Sienkowska, Monika J.; Heiney, Paul A.

    2006-01-01

    The self-assembly of the dendritic dipeptides (4-3,4-3,5)nG2-CH2-Boc-l-Tyr-l-Ala-OMe and their achiral dendritic alcohol (4-3,4-3,5)nG2-CH2OH precursors, both with n = 1–16, where n represents the number of methylenic units in the alkyl groups of the dendron, are reported. All chiral dendritic dipeptides and achiral dendritic alcohols self-assemble into helical porous columns that are stable in both solution and solid state. The pore diameter (Dpore) of the columns self-assembled from dendrit...

  1. Characteristics of the Dendrite Growth in the Electrochemical Alane Production Process

    Directory of Open Access Journals (Sweden)

    Park Hyun-Kyu

    2016-01-01

    Full Text Available The electrochemical alane production process was proposed for a feasible production of alane. The operation of process was difficult because of short circuit by a dendrite growth in the reactor. Therefore, characteristics of the dendrite growth in the process were investigated. We conducted the electrochemical alane production process using Teflon block for inhibition of the dendrite growth. The obtained dendrite was characterized by XRD, SEM and ICP-AES. It was concluded that the dendrite growth was attributed to a melting and agglomeration of Al fine particles existed in the solution.

  2. Disruptions, Disruptivity, and Safer Operating Windows in the High-β Spherical Torus NSTX

    Energy Technology Data Exchange (ETDEWEB)

    Gerhardt, S P; Diallo, A; Gates, D; LeBlanc, B P; Menard, J E; Mueller, D; Sabbagh, S A; Soukhanovskii, V; Tritz, K

    2012-09-27

    This paper discusses disruption rates, disruption causes, and disruptivity statistics in the high- βN National Spherical Torus Experiment (NSTX) [M. Ono, et al. Nuclear Fusion 40, 557 (2000)]. While the overall disruption rate is rather high, configurations with high βN , moderate q*, strong boundary shaping, sufficient rotation, and broad pressure and current profiles are found to have the lowest disruptivity; active n=1 control further reduces the disruptivity. The disruptivity increases rapidly for q*<2.7, which is substantially above the ideal MHD current limit. In quiescent conditions, qmin >1.25 is generally acceptable for avoiding the onset of core rotating n=1 kink/tearing modes; when EPM and ELM disturbances are present, the required qmin for avoiding those modes is raised to ~1.5. The current ramp and early flat-top phase of the discharges are prone to n=1 core rotating modes locking to the wall, leading to a disruption. Small changes to the discharge fueling during this phase can often mitigate the rotation damping associated with these modes and eliminate the disruption. The largest stored energy disruptions are those that occur at high current when a plasma current rampdown is initiated incorrectly.

  3. Mesenchymal stem cells abrogate experimental asthma by altering dendritic cell function.

    Science.gov (United States)

    Zeng, Shao-Lin; Wang, Li-Hui; Li, Ping; Wang, Wei; Yang, Jiong

    2015-08-01

    Mesenchymal stem cells (MSCs) have been investigated in the treatment of numerous autoimmune diseases. However, the immune properties of MSCs on the development of asthma have remained to be fully elucidated. Airway dendritic cells (DCs) have an important role in the pathogenesis of allergic asthma, and disrupting their function may be a novel therapeutic approach. The present study used a mouse model of asthma to demonstrate that transplantation of MSCs suppressed features of asthma by targeting the function of lung myeloid DCs. MSCs suppressed the maturation and migration of lung DCs to the mediastinal lymph nodes, and thereby reducing the allergen-specific T helper type 2 (Th2) response in the nodes. In addition, MSC-treated DCs were less potent in activating naive and effector Th2 cells and the capacity of producing chemokine (C-C motif) ligand 17 (CCL17) and CCL22, which are chemokines attracting Th2 cells, to the airways was reduced. These results supported that MSCs may be used as a potential treatment for asthma. PMID:25936350

  4. Bisphenol-A rapidly promotes dynamic changes in hippocampal dendritic morphology through estrogen receptor-mediated pathway by concomitant phosphorylation of NMDA receptor subunit NR2B

    International Nuclear Information System (INIS)

    Bisphenol-A (BPA) is known to be a potent endocrine disrupter. Evidence is emerging that estrogen exerts a rapid influence on hippocampal synaptic plasticity and the dendritic spine density, which requires activation of NMDA receptors. In the present study, we investigated the effects of BPA (ranging from 1 to 1000 nM), focusing on the rapid dynamic changes in dendritic filopodia and the expressions of estrogen receptor (ER) β and NMDA receptor, as well as the phosphorylation of NMDA receptor subunit NR2B in the cultured hippocampal neurons. A specific ER antagonist ICI 182,780 was used to examine the potential involvement of ERs. The results demonstrated that exposure to BPA (ranging from 10 to 1000 nM) for 30 min rapidly enhanced the motility and the density of dendritic filopodia in the cultured hippocampal neurons, as well as the phosphorylation of NR2B (pNR2B), though the expressions of NMDA receptor subunits NR1, NR2B, and ERβ were not changed. The antagonist of ERs completely inhibited the BPA-induced increases in the filopodial motility and the number of filopodia extending from dendrites. The increased pNR2B induced by BPA (100 nM) was also completely eliminated. Furthermore, BPA attenuated the effects of 17β-estradiol (17β-E2) on the dendritic filopodia outgrowth and the expression of pNR2B when BPA was co-treated with 17β-E2. The present results suggest that BPA, like 17β-E2, rapidly results in the enhanced motility and density of dendritic filopodia in the cultured hippocampal neurons with the concomitant activation of NMDA receptor subunit NR2B via an ER-mediated signaling pathway. Meanwhile, BPA suppressed the enhancement effects of 17β-E2 when it coexists with 17β-E2. These results provided important evidence suggesting the neurotoxicity of the low levels of BPA during the early postnatal development of the brain.

  5. Signal transfer in passive dendrites with nonuniform membrane conductance.

    Science.gov (United States)

    London, M; Meunier, C; Segev, I

    1999-10-01

    In recent years it became clear that dendrites possess a host of ion channels that may be distributed nonuniformly over their membrane surface. In cortical pyramids, for example, it was demonstrated that the resting membrane conductance G(m)(x) is higher (the membrane is "leakier") at distal dendritic regions than at more proximal sites. How does this spatial nonuniformity in G(m)(x) affect the input-output function of the neuron? The present study aims at providing basic insights into this question. To this end, we have analytically studied the fundamental effects of membrane non-uniformity in passive cable structures. Keeping the total membrane conductance over a given modeled structure fixed (i.e., a constant number of passive ion channels), the classical case of cables with uniform membrane conductance is contrasted with various nonuniform cases with the following general conclusions. (1) For cylindrical cables with "sealed ends," monotonic increase in G(m)(x) improves voltage transfer from the input location to the soma. The steeper the G(m)(x), the larger the improvement. (2) This effect is further enhanced when the stimulation is distal and consists of a synaptic input rather than a current source. (3) Any nonuniformity in G(m)(x) decreases the electrotonic length, L, of the cylinder. (4) The system time constant tau(0) is larger in the nonuniform case than in the corresponding uniform case. (5) When voltage transients relax with tau(0), the dendritic tree is not isopotential in the nonuniform case, at variance with the uniform case. The effect of membrane nonuniformity on signal transfer in reconstructed dendritic trees and on the I/f relation of the neuron is also considered, and experimental methods for assessing membrane nonuniformity in dendrites are discussed.

  6. Differential Dendritic Integration of Synaptic Potentials and Calcium in Cerebellar Interneurons.

    Science.gov (United States)

    Tran-Van-Minh, Alexandra; Abrahamsson, Therése; Cathala, Laurence; DiGregorio, David A

    2016-08-17

    Dendritic voltage integration determines the transformation of synaptic inputs into output firing, while synaptic calcium integration drives plasticity mechanisms thought to underlie memory storage. Dendritic calcium integration has been shown to follow the same synaptic input-output relationship as dendritic voltage, but whether similar operations apply to neurons exhibiting sublinear voltage integration is unknown. We examined the properties and cellular mechanisms of these dendritic operations in cerebellar molecular layer interneurons using dendritic voltage and calcium imaging, in combination with synaptic stimulation or glutamate uncaging. We show that, while synaptic potentials summate sublinearly, concomitant dendritic calcium signals summate either linearly or supralinearly depending on the number of synapses activated. The supralinear dendritic calcium triggers a branch-specific, short-term suppression of neurotransmitter release that alters the pattern of synaptic activation. Thus, differential voltage and calcium integration permits dynamic regulation of neuronal input-output transformations without altering intrinsic nonlinear integration mechanisms.

  7. A Rayleigh number based dendrite fragmentation criterion for detachment of solid crystals during solidification

    International Nuclear Information System (INIS)

    Movement of solid crystals in the form of dendrite fragments causes severe macro-segregation in solidified products. Dendrite fragmentation in the developing mushy zone occurs as a result of remelting (causing dissolution) and subsequent breakage of dendritic side arms from the dendritic stalks. An understanding of the mechanisms of dendrite fragmentation is essential for predicting the transport of fragmented solid crystals for possible control of macro-segregation. In this work, a Rayleigh number based fragmentation criterion is developed for detachment of dendrites from the developing mushy zone, which determines the conditions favourable for fragmentation of dendrites. The Rayleigh number, defined in this paper, measures the ratio of the driving buoyancy force for the flow in the mushy zone to the retarding frictional force associated with the permeability of the mush. The criterion developed is a function of the concentration difference, liquid fraction, permeability, growth rate of mushy layer and thermophysical properties of the material

  8. Morphological analysis of dendrites and spines by hybridization of ridge detection with twin support vector machine.

    Science.gov (United States)

    Wang, Shuihua; Chen, Mengmeng; Li, Yang; Shao, Ying; Zhang, Yudong; Du, Sidan; Wu, Jane

    2016-01-01

    Dendritic spines are described as neuronal protrusions. The morphology of dendritic spines and dendrites has a strong relationship to its function, as well as playing an important role in understanding brain function. Quantitative analysis of dendrites and dendritic spines is essential to an understanding of the formation and function of the nervous system. However, highly efficient tools for the quantitative analysis of dendrites and dendritic spines are currently undeveloped. In this paper we propose a novel three-step cascaded algorithm-RTSVM- which is composed of ridge detection as the curvature structure identifier for backbone extraction, boundary location based on differences in density, the Hu moment as features and Twin Support Vector Machine (TSVM) classifiers for spine classification. Our data demonstrates that this newly developed algorithm has performed better than other available techniques used to detect accuracy and false alarm rates. This algorithm will be used effectively in neuroscience research. PMID:27547530

  9. Differential Dendritic Integration of Synaptic Potentials and Calcium in Cerebellar Interneurons.

    Science.gov (United States)

    Tran-Van-Minh, Alexandra; Abrahamsson, Therése; Cathala, Laurence; DiGregorio, David A

    2016-08-17

    Dendritic voltage integration determines the transformation of synaptic inputs into output firing, while synaptic calcium integration drives plasticity mechanisms thought to underlie memory storage. Dendritic calcium integration has been shown to follow the same synaptic input-output relationship as dendritic voltage, but whether similar operations apply to neurons exhibiting sublinear voltage integration is unknown. We examined the properties and cellular mechanisms of these dendritic operations in cerebellar molecular layer interneurons using dendritic voltage and calcium imaging, in combination with synaptic stimulation or glutamate uncaging. We show that, while synaptic potentials summate sublinearly, concomitant dendritic calcium signals summate either linearly or supralinearly depending on the number of synapses activated. The supralinear dendritic calcium triggers a branch-specific, short-term suppression of neurotransmitter release that alters the pattern of synaptic activation. Thus, differential voltage and calcium integration permits dynamic regulation of neuronal input-output transformations without altering intrinsic nonlinear integration mechanisms. PMID:27537486

  10. Thyroid disrupting chemicals: Mechanisms and mixtures

    Science.gov (United States)

    Environmental contaminants are known to act as thyroid disrupting chemicals (TDCs). Broadly defined, TDCs are xenobiotics that alter the structure or function of the thyroid gland, alter regulatory enzymes associated with thyroid hormone (TH) homeostasis, or change circulating o...

  11. Glaciological parameters of disruptive event analysis

    International Nuclear Information System (INIS)

    The following disruptive events caused by ice sheets are considered: continental glaciation, erosion, loading and subsidence, deep ground water recharge, flood erosion, isostatic rebound rates, melting, and periodicity of ice ages

  12. Double tidal disruptions in galactic nuclei

    CERN Document Server

    Mandel, Ilya

    2015-01-01

    A star on a nearly radial trajectory approaching a massive black hole (MBH) gets tidally disrupted if it comes sufficiently close to the MBH. Here we explore what happens to binary stars whose centers of mass approach the MBH on nearly radial orbits. The interaction with the MBH often leads to both stars being disrupted in sequence. We argue that such events could produce light curves that are substantially different from those of the single disruptions, with possible features such as two local maxima. Tidal forces from the MBH can also lead the binary components to collide; these merger products can form highly magnetized stars, whose subsequent tidal disruption may enable prompt jet formation.

  13. Passive runaway electron suppression in tokamak disruptions

    International Nuclear Information System (INIS)

    Runaway electrons created in disruptions pose a serious problem for tokamaks with large current. It would be desirable to have a runaway electron suppression method which is passive, i.e., a method that does not rely on an uncertain disruption prediction system. One option is to let the large electric field inherent in the disruption drive helical currents in the wall. This would create ergodic regions in the plasma and increase the runaway losses. Whether these regions appear at a suitable time and place to affect the formation of the runaway beam depends on disruption parameters, such as electron temperature and density. We find that it is difficult to ergodize the central plasma before a beam of runaway current has formed. However, the ergodic outer region will make the Ohmic current profile contract, which can lead to instabilities that yield large runaway electron losses

  14. Shell Galaxies, Dynamical Friction, and Dwarf Disruption

    CERN Document Server

    Ebrova, Ivana; Canalizo, Gabriela; Bennert, Nicola; Jilkova, Lucie

    2009-01-01

    Using N-body simulations of shell galaxies created in nearly radial minor mergers, we investigate the error of collision dating, resulting from the neglect of dynamical friction and of gradual disruption of the cannibalized dwarf.

  15. Towards a Framework of Digital Platform Disruption

    DEFF Research Database (Denmark)

    Kazan, Erol; Tan, Chee-Wee; Lim, Eric T. K.

    2014-01-01

    Digital platforms are disruptive information technology (IT) artifacts that erode conventional business logic associated with traditional market structures. This paper presents a framework for examining the disruptive potential of digital platforms whereby we postulate that the strategic interplay...... of governance regimes and platform layers is deterministic of whether disruptive derivatives are permitted to flourish. This framework has been employed in a comparative case study between centralized (i.e., PayPal) and decentralized (i.e., Coinkite) digital payment platforms to illustrate its applicability...... and yield propositions on the nature and impact of digital platform disruptions. Preliminary findings indicate that centralized digital platforms attempt to create unique configurals to obtain monopolistic power by tightly coupling platform layers, which are difficult to replicate. Conversely, decentralized...

  16. Disruptive Innovation in Chinese and Indian Businesses

    DEFF Research Database (Denmark)

    markets, has made these emerging economies fertile ground for developing and applying disruptive innovations. A novel mix of key attributes distinctive from those of established technologies or business models, disruptive innovations are typically inferior, yet affordable and "good-enough" products...... or services, which originate in lower-end market segments, but later move up to compete with those provided by incumbent firms. This book sheds new light on disruptive innovations both from and for the bottom of the pyramid in China and India, from the point of view of local entrepreneurs and international...... firms seeking to operate their businesses there. It covers both the theoretical and practical implications of disruptive innovation using conceptual frameworks alongside detailed case studies, whilst also providing a comparison of conditions and strategic options in India and China. Further, unlike...

  17. Report on Criteria for Endocrine Disrupters

    DEFF Research Database (Denmark)

    Holbech, Henrik

    2011-01-01

    This report has been prepared by the Danish Centre on Endocrine Disrupters as a project contracted by the Danish Environmental Protection Agency. The Danish Centre on Endocrine Disrupters is an interdisciplinary scientific network without walls. The main purpose of the Centre is to build and gather...... new knowledge on endocrine disrupters with the focus on providing information requested for the preventive work of the regulatory authorities. The Centre is financed by the Ministry of the Environment and the scientific work programme is followed by an international scientific advisory board....... The overall aim of this project is to provide a science based proposal for criteria for endocrine disrupters. The terms of reference for the project specify elements to be included and/or addressed when developing the criteria (Annex 1). Also, several international reports and papers dealing with assessment...

  18. 75 FR 30306 - Responding To Disruptive Patients

    Science.gov (United States)

    2010-06-01

    ... performance of official duties by Government employees.'' The sole enforcement mechanism provided by paragraph... opposes the use of punishment in the management of disruptive patients. Instead, it reflects the view...

  19. Serum inducible kinase is a positive regulator of cortical dendrite development and is required for BDNF-promoted dendritic arborization

    Institute of Scientific and Technical Information of China (English)

    Shun-Ling Guo; Guo-He Tan; Shuai Li; Xue-Wen Cheng; Ya Zhou; Yun-Fang Jia; Hui Xiong; Jiong Tao; Zhi-Qi Xiong

    2012-01-01

    Serum inducible kinase (SNK),also known as (p)olo-(l)ike (k)inase 2 (PLK2),is a known regulator of mitosis,synaptogenesis and synaptic homeostasis.However,its role in early cortical development is unknown.Herein,we show that snk is expressed in the cortical plate from embryonic day 14,but not in the ventricular/subventricular zones (VZ/SVZ),and SNK protein localizes to the soma and dendrites of cultured immature cortical neurons.Loss of SNK impaired dendritic but not axonal arborization in a dose-dependent manner and overexpression had opposite effects,both in vitro and in vivo.Overexpression of SNK also caused abnormal branching of the leading process of migrating cortical neurons in electroporated cortices.The kinase activity was necessary for these effects.Extracellular signalregulated kinase (ERK) pathway activity downstream of brain-derived neurotrophic factor (BDNF) stimulation led to increases in SNK protein expression via transcriptional regulation,and this upregulation was necessary for the growth-promoting effect of BDNF on dendritic arborization.Taken together,our results indicate that SNK is essential for dendrite morphogenesis in cortical neurons.

  20. The Relative Ineffectiveness of Criminal Network Disruption

    OpenAIRE

    Duijn, P.A.C.; Kashirin, V.; Sloot, P.M.A.

    2014-01-01

    Researchers, policymakers and law enforcement agencies across the globe struggle to find effective strategies to control criminal networks. The effectiveness of disruption strategies is known to depend on both network topology and network resilience. However, as these criminal networks operate in secrecy, data-driven knowledge concerning the effectiveness of different criminal network disruption strategies is very limited. By combining computational modeling and social network analysis with u...

  1. Anastomotic disruption after large bowel resection

    Institute of Scientific and Technical Information of China (English)

    Mohammad U NasirKhan; Farshad Abir; Walter Longo; Robert Kozol

    2006-01-01

    Anastomotic disruption is a feared and serious complication of colon surgery. Decades of research have identified factors favoring successful healing of anastomoses as well as risk factors for anastomotic disruption. However, some factors, such as the role of mechanical bowel preparation, remain controversial.Despite proper caution and excellent surgical technique,some anastomotic leaks are inevitable. The rapid identification of anastomotic leaks and the timely treatment in these cases are paramount.

  2. BUSINESS MODEL PATTERNS FOR DISRUPTIVE TECHNOLOGIES

    OpenAIRE

    BENJAMIN AMSHOFF; CHRISTIAN DÜLME; JULIAN ECHTERFELD; JÜRGEN GAUSEMEIER

    2015-01-01

    Companies nowadays face a myriad of business opportunities as a direct consequence of manifold disruptive technology developments. As a basic characteristic, disruptive technologies lead to a severe shift in value-creation networks giving rise to new market segments. One of the key challenges is to anticipate the business logics within these nascent and formerly unknown markets. Business model patterns promise to tackle this challenge. They can be interpreted as proven business model elements...

  3. On asymmetric collisions with large disruption parameters

    International Nuclear Information System (INIS)

    Collisions between a weak electron bunch and a strong positron bunch are studied within a flat model. Electrons are tracked through the transverse space charge field of the positron bunch, and it is shown that positrons in a storage ring may remain stable after asymmetric collisions with a weak electron bunch in spite of large values of the electron disruption parameter. The plasma oscillations that affect collisions with large disruption parameters may be suppressed by properly matching the electrons. 8 refs., 5 figs

  4. Sleep and circadian rhythm disruption in schizophrenia†

    OpenAIRE

    Wulff, Katharina; Dijk, Derk-Jan; Middleton, Benita; Foster, Russell G.; Joyce, Eileen M.

    2012-01-01

    Background Sleep disturbances comparable with insomnia occur in up to 80% of people with schizophrenia, but very little is known about the contribution of circadian coordination to these prevalent disruptions. Aims A systematic exploration of circadian time patterns in individuals with schizophrenia with recurrent sleep disruption. Method We examined the relationship between sleep-wake activity, recorded actigraphically over 6 weeks, along with ambient light exposure and simultaneous circadia...

  5. Airline Disruption Management - Perspectives, Experiences and Outlook

    OpenAIRE

    Kohl, Niklas; Larsen, Allan; Larsen, Jesper; Ross, Alex; Tiourine, Sergey

    2004-01-01

    Over the past decade, airlines have become more concerned with developing an optimal flight schedule, with very little slack left to accommodate for any form of variation from the optimal solution. During operation the planned schedules often have to be revised due to disruptions caused by for example severe weather, technical problems and crew sickness. Thus, the field of Airline Disruption Management has emerged within the past few years. The increased focus on cutting cost at the major air...

  6. Anastomotic disruption after large bowel resection

    OpenAIRE

    NasirKhan, Mohammad U; Abir, Farshad; Longo, Walter; Kozol, Robert

    2006-01-01

    Anastomotic disruption is a feared and serious complication of colon surgery. Decades of research have identified factors favoring successful healing of anastomoses as well as risk factors for anastomotic disruption. However, some factors, such as the role of mechanical bowel preparation, remain controversial. Despite proper caution and excellent surgical technique, some anastomotic leaks are inevitable. The rapid identification of anastomotic leaks and the timely treatment in these cases are...

  7. ENDOCRINE DISRUPTING EFFECTS OF BUTYLPARABEN: A REVIEW

    OpenAIRE

    Pallabi Goswami; J.C Kalita

    2013-01-01

    In recent years, there has been an increasing concern in the field of endocrine disruption over the presence of various endocrine disrupting chemicals in Pharmaceuticals and Personal care products (PPCPs). This concern has also been as PPCPs are most widely used and had led to introduction of thousands of new and complex chemicals that enter the environment in large quantities. The effect of the chemicals has not only been restricted to human who are exposed directly to the chemicals or the a...

  8. Disruption Management in Passenger Railway Transportation

    DEFF Research Database (Denmark)

    Jespersen-Groth, Julie; Potthoff, Daniel; Clausen, Jens;

    This paper deals with disruption management in passenger railway transportation. In the disruption management process, many actors belonging to different organizations play a role. In this paper we therefore describe the process itself and the roles of the different actors. Furthermore, we discus...... for related problems in the airline world are discussed as well. Finally, we address the integration of the re-scheduling processes of the timetable, and the resources rolling stock and crew....

  9. Dynamics of intrinsic dendritic calcium signaling during tonic firing of thalamic reticular neurons.

    Directory of Open Access Journals (Sweden)

    Patrick Chausson

    Full Text Available The GABAergic neurons of the nucleus reticularis thalami that control the communication between thalamus and cortex are interconnected not only through axo-dendritic synapses but also through gap junctions and dendro-dendritic synapses. It is still unknown whether these dendritic communication processes may be triggered both by the tonic and the T-type Ca(2+ channel-dependent high frequency burst firing of action potentials displayed by nucleus reticularis neurons during wakefulness and sleep, respectively. Indeed, while it is known that activation of T-type Ca(2+ channels actively propagates throughout the dendritic tree, it is still unclear whether tonic action potential firing can also invade the dendritic arborization. Here, using two-photon microscopy, we demonstrated that dendritic Ca(2+ responses following somatically evoked action potentials that mimic wake-related tonic firing are detected throughout the dendritic arborization. Calcium influx temporally summates to produce dendritic Ca(2+ accumulations that are linearly related to the duration of the action potential trains. Increasing the firing frequency facilitates Ca(2+ influx in the proximal but not in the distal dendritic compartments suggesting that the dendritic arborization acts as a low-pass filter in respect to the back-propagating action potentials. In the more distal compartment of the dendritic tree, T-type Ca(2+ channels play a crucial role in the action potential triggered Ca(2+ influx suggesting that this Ca(2+ influx may be controlled by slight changes in the local dendritic membrane potential that determine the T-type channels' availability. We conclude that by mediating Ca(2+ dynamic in the whole dendritic arborization, both tonic and burst firing of the nucleus reticularis thalami neurons might control their dendro-dendritic and electrical communications.

  10. Mechanistic evaluation of endocrine disrupting chemicals

    DEFF Research Database (Denmark)

    Taxvig, Camilla

    BACKGROUND: This PhD project is part of the research area concerning effects of endocrine disrupters at the National Food Institute at DTU in Denmark. Endocrine disrupting chemicals (EDCs) have proved to be important for improper development of the male reproductive organs and subsequent for the ...... metabolising system using liver S9 mixtures or hepatic rat microsomes could be a convenient method for the incorporation of metabolic aspects into in vitro testing for endocrine disrupting effects.......BACKGROUND: This PhD project is part of the research area concerning effects of endocrine disrupters at the National Food Institute at DTU in Denmark. Endocrine disrupting chemicals (EDCs) have proved to be important for improper development of the male reproductive organs and subsequent......, to be able to detect effects and predict mixture effects. In addition, a new hypothesis have emerge concerning a potential role of exposure to endocrine disrupting chemicals, and the development of obesity and obesity related diseases. AIM: This PhD project aimed to gain more information regarding...

  11. Airline Disruption Management - Perspectives, Experiences and Outlook

    DEFF Research Database (Denmark)

    Kohl, Niklas; Larsen, Allan; Larsen, Jesper;

    2004-01-01

    Over the past decade, airlines have become more concerned with developing an optimal flight schedule, with very little slack left to accommodate for any form of variation from the optimal solution. During operation the planned schedules often have to be revised due to disruptions caused by for ex......Over the past decade, airlines have become more concerned with developing an optimal flight schedule, with very little slack left to accommodate for any form of variation from the optimal solution. During operation the planned schedules often have to be revised due to disruptions caused...... by for example severe weather, technical problems and crew sickness. Thus, the field of Airline Disruption Management has emerged within the past few years. The increased focus on cutting cost at the major airlines has intensified the interest in the development of new and cost e cient methods to handle airline...... disruptions. The purpose of this paper is twofold. In the first part it o ers an introduction to airline disruption management, provides the readers with a description of the planning processes and delivers a detailed overview of the numerous aspects of airline disruption management. In the second part we...

  12. Airline Disruption Management - Perspectives, Experiences and Outlook

    DEFF Research Database (Denmark)

    Kohl, Niklas; Larsen, Allan; Larsen, Jesper;

    2007-01-01

    Over the past decade, airlines have become more concerned with developing an optimal flight schedule, with very little slack left to accommodate for any form of variation from the optimal solution. During operation the planned schedules often have to be revised due to disruptions caused by for ex......Over the past decade, airlines have become more concerned with developing an optimal flight schedule, with very little slack left to accommodate for any form of variation from the optimal solution. During operation the planned schedules often have to be revised due to disruptions caused...... by for example severe weather, technical problems and crew sickness. Thus, the field of Airline Disruption Management has emerged within the past few years. The increased focus on cutting cost at the major airlines has intensified the interest in the development of new and cost efficient methods to handle...... airline disruptions. The purpose of this paper is twofold. In the first part it offers an introduction to airline disruption management provides the readers with a description of the planning processes and delivers a detailed overview of the numerous aspects of airline disruption management. In the second...

  13. Dendritic cell SIRPα regulates homeostasis of dendritic cells in lymphoid organs.

    Science.gov (United States)

    Washio, Ken; Kotani, Takenori; Saito, Yasuyuki; Respatika, Datu; Murata, Yoji; Kaneko, Yoriaki; Okazawa, Hideki; Ohnishi, Hiroshi; Fukunaga, Atsushi; Nishigori, Chikako; Matozaki, Takashi

    2015-06-01

    Signal regulatory protein α (SIRPα), an immunoglobulin superfamily protein that is expressed predominantly in myeloid lineage cells such as dendritic cells (DCs) or macrophages, mediates cell-cell signaling. In the immune system, SIRPα is thought to be important for homeostasis of DCs, but it remains unclear whether SIRPα intrinsic to DCs is indeed indispensable for such functional role. Thus, we here generated the mice, in which SIRPα was specifically ablated in CD11c(+) DCs (Sirpa(Δ) (DC) ). Sirpa(Δ) (DC) mice manifested a marked reduction of CD4(+) CD8α(-) conventional DCs (cDCs) in the secondary lymphoid organs, as well as of Langerhans cells in the epidermis. Such reduction of cDCs in Sirpa(Δ) (DC) mice was comparable to that apparent with the mice, in which SIRPα was systemically ablated. Expression of SIRPα in DCs was well correlated with that of either endothelial cell-selective adhesion molecule (ESAM) or Epstein-Barr virus-induced molecule 2 (EBI2), both of which were also implicated in the regulation of DC homeostasis. Indeed, ESAM(+) or EBI2(+) cDCs were markedly reduced in the spleen of Sirpa(Δ) (DC) mice. Thus, our results suggest that SIRPα intrinsic to CD11c(+) DCs is essential for homeostasis of cDCs in the secondary lymphoid organs and skin.

  14. REMOD: a computational tool for remodeling neuronal dendrites

    Directory of Open Access Journals (Sweden)

    Panagiotis Bozelos

    2014-05-01

    Full Text Available In recent years, several modeling studies have indicated that dendritic morphology is a key determinant of how individual neurons acquire a unique signal processing profile. The highly branched dendritic structure that originates from the cell body, explores the surrounding 3D space in a fractal-like manner, until it reaches a certain amount of complexity. Its shape undergoes significant alterations not only in various neuropathological conditions, but in physiological, too. Yet, despite the profound effect that these alterations can have on neuronal function, the causal relationship between structure and function remains largely elusive. The lack of a systematic approach for remodeling neuronal cells and their dendritic trees is a key limitation that contributes to this problem. In this context, we developed a computational tool that allows the remodeling of any type of neurons, given a set of exemplar morphologies. The tool is written in Python and provides a simple GUI that guides the user through various options to manipulate selected neuronal morphologies. It provides the ability to load one or more morphology files (.swc or .hoc and choose specific dendrites to operate one of the following actions: shrink, remove, extend or branch (as shown in Figure 1. The user retains complete control over the extent of each alteration and if a chosen action is not possible due to pre-existing structural constraints, appropriate warnings are produced. Importantly, the tool can also be used to extract morphology statistics for one or multiple morphologies, including features such as the total dendritic length, path length to the root, branch order, diameter tapering, etc. Finally, an experimental utility enables the user to remodel entire dendritic trees based on preloaded statistics from a database of cell-type specific neuronal morphologies. To our knowledge, this is the first tool that allows (a the remodeling of existing –as opposed to the de novo

  15. Mechanical algal disruption for efficient biodiesel extraction

    Science.gov (United States)

    Krehbiel, Joel David

    Biodiesel from algae provides several benefits over current biodiesel feedstocks, but the energy requirements of processing algae into a useable fuel are currently so high as to be prohibitive. One route to improving this is via disruption of the cells prior to lipid extraction, which can significantly increase energy recovery. Unfortunately, several obvious disruption techniques require more energy than can be gained. This dissertation examines the use of microbubbles to improve mechanical disruption of algal cells using experimental, theoretical, and computational methods. New laboratory experiments show that effective ultrasonic disruption of algae is achieved by adding microbubbles to an algal solution. The configuration studied flows the solution through a tube and insonifies a small section with a high-pressure ultrasound wave. Previous biomedical research has shown effective cell membrane damage on animal cells with similar methods, but the present research is the first to extend such study to algal cells. Results indicate that disruption increases with peak negative pressure between 1.90 and 3.07 MPa and with microbubble concentration up to 12.5 x 107 bubbles/ml. Energy estimates of this process suggest that it requires only one-fourth the currently most-efficient laboratory-scale disruption process. Estimates of the radius near each bubble that causes disruption (i.e. the disruption radius) suggest that it increases with peak negative pressure and is near 9--20 microm for all cases tested. It is anticipated that these procedures can be designed for better efficiency and efficacy, which will be facilitated by identifying the root mechanisms of the bubble-induced disruption. We therefore examine whether bubble expansion alone creates sufficient cell deformation for cell rupture. The spherically-symmetric Marmottant model for bubble dynamics allows estimation of the flow regime under experimental conditions. Bubble expansion is modeled as a point source of

  16. Computational study of electro-convection effects on dendrite growth in batteries

    Science.gov (United States)

    Tan, Jinwang; Ryan, Emily M.

    2016-08-01

    Dendrite formation on the anode surface of a battery is closely related to the safety and capacity of high energy density batteries, thus suppressing dendrite growth will significantly improve the performance of batteries. Many experimental reports reveal that convection near the dendrite nucleation site can change the local mass transport, and ultimately affect dendrite growth. Investigation of the convection effect in batteries will guide the development of strategies to suppress dendrite growth in a convective electrolyte. Most of the existing electro-convection computational models for dendrite growth studies are based on Eulerian frameworks. These methods have difficulty modeling the moving boundaries associated with dendrite growth and are less computationally efficient in simulating convective fluid motion. In this paper we adopt a mesh-free particle based Lagrangian method to address the challenges of previous grid based Eulerian electro-convection models. The developed model is verified by comparison to analytical solutions, including verification of ion migration and the electric potential. Simulation results show that the predicted dendrite growth and electro-convective flow patterns compare well with experimental results during early dendrite growth stages. Parametric studies reveal that low viscosity electrolytes suppress the dendrite growth by increasing the mass transport of ions near the anode/electrolyte interface.

  17. Spiny Neurons of Amygdala, Striatum and Cortex Use Dendritic Plateau Potentials to Detect Network UP States

    Directory of Open Access Journals (Sweden)

    Katerina D Oikonomou

    2014-09-01

    Full Text Available Spiny neurons of amygdala, striatum, and cerebral cortex share four interesting features: [1] they are the most abundant cell type within their respective brain area, [2] covered by thousands of thorny protrusions (dendritic spines, [3] possess high levels of dendritic NMDA conductances, and [4] experience sustained somatic depolarizations in vivo and in vitro (UP states. In all spiny neurons of the forebrain, adequate glutamatergic inputs generate dendritic plateau potentials (dendritic UP states characterized by (i fast rise, (ii plateau phase lasting several hundred milliseconds and (iii abrupt decline at the end of the plateau phase. The dendritic plateau potential propagates towards the cell body decrementally to induce a long-lasting (longer than 100 ms, most often 200 – 800 ms steady depolarization (~20 mV amplitude, which resembles a neuronal UP state. Based on voltage-sensitive dye imaging, the plateau depolarization in the soma is precisely time-locked to the regenerative plateau potential taking place in the dendrite. The somatic plateau rises after the onset of the dendritic voltage transient and collapses with the breakdown of the dendritic plateau depolarization. We hypothesize that neuronal UP states in vivo reflect the occurrence of dendritic plateau potentials (dendritic UP states. We propose that the somatic voltage waveform during a neuronal UP state is determined by dendritic plateau potentials. A mammalian spiny neuron uses dendritic plateau potentials to detect and transform coherent network activity into a ubiquitous neuronal UP state. The biophysical properties of dendritic plateau potentials allow neurons to quickly attune to the ongoing network activity, as well as secure the stable amplitudes of successive UP states.

  18. Dendritic thickness: a morphometric parameter to classify mouse retinal ganglion cells

    Directory of Open Access Journals (Sweden)

    L.D. Loopuijt

    2007-10-01

    Full Text Available To study the dendritic morphology of retinal ganglion cells in wild-type mice we intracellularly injected these cells with Lucifer yellow in an in vitro preparation of the retina. Subsequently, quantified values of dendritic thickness, number of branching points and level of stratification of 73 Lucifer yellow-filled ganglion cells were analyzed by statistical methods, resulting in a classification into 9 groups. The variables dendritic thickness, number of branching points per cell and level of stratification were independent of each other. Number of branching points and level of stratification were independent of eccentricity, whereas dendritic thickness was positively dependent (r = 0.37 on it. The frequency distribution of dendritic thickness tended to be multimodal, indicating the presence of at least two cell populations composed of neurons with dendritic diameters either smaller or larger than 1.8 µm ("thin" or "thick" dendrites, respectively. Three cells (4.5% were bistratified, having thick dendrites, and the others (95.5% were monostratified. Using k-means cluster analysis, monostratified cells with either thin or thick dendrites were further subdivided according to level of stratification and number of branching points: cells with thin dendrites were divided into 2 groups with outer stratification (0-40% and 2 groups with inner (50-100% stratification, whereas cells with thick dendrites were divided into one group with outer and 3 groups with inner stratification. We postulate, that one group of cells with thin dendrites resembles cat ß-cells, whereas one group of cells with thick dendrites includes cells that resemble cat a-cells.

  19. Nectin-1 spots regulate the branching of olfactory mitral cell dendrites.

    Science.gov (United States)

    Fujiwara, Takeshi; Inoue, Takahito; Maruo, Tomohiko; Rikitake, Yoshiyuki; Ieki, Nao; Mandai, Kenji; Kimura, Kazushi; Kayahara, Tetsuro; Wang, Shujie; Itoh, Yu; Sai, Kousyoku; Mori, Masahiro; Mori, Kensaku; Takai, Yoshimi; Mizoguchi, Akira

    2015-09-01

    Olfactory mitral cells extend lateral secondary dendrites that contact the lateral secondary and apical primary dendrites of other mitral cells in the external plexiform layer (EPL) of the olfactory bulb. The lateral dendrites further contact granule cell dendrites, forming dendrodendritic reciprocal synapses in the EPL. These dendritic structures are critical for odor information processing, but it remains unknown how they are formed. We recently showed that the immunoglobulin-like cell adhesion molecule nectin-1 constitutes a novel adhesion apparatus at the contacts between mitral cell lateral dendrites, between mitral cell lateral and apical dendrites, and between mitral cell lateral dendrites and granule cell dendritic spine necks in the deep sub-lamina of the EPL of the developing mouse olfactory bulb and named them nectin-1 spots. We investigated here the role of the nectin-1 spots in the formation of dendritic structures in the EPL of the mouse olfactory bulb. We showed that in cultured nectin-1-knockout mitral cells, the number of branching points of mitral cell dendrites was reduced compared to that in the control cells. In the deep sub-lamina of the EPL in the nectin-1-knockout olfactory bulb, the number of branching points of mitral cell lateral dendrites and the number of dendrodendritic reciprocal synapses were reduced compared to those in the control olfactory bulb. These results indicate that the nectin-1 spots regulate the branching of mitral cell dendrites in the deep sub-lamina of the EPL and suggest that the nectin-1 spots are required for odor information processing in the olfactory bulb. PMID:26169026

  20. Mussel-inspired dendritic polymers as universal multifunctional coatings.

    Science.gov (United States)

    Wei, Qiang; Achazi, Katharina; Liebe, Hendrik; Schulz, Andrea; Noeske, Paul-Ludwig Michael; Grunwald, Ingo; Haag, Rainer

    2014-10-20

    A rapid and universal approach for multifunctional material coatings was developed based on a mussel-inspired dendritic polymer. This new kind of polymer mimics not only the functional groups of mussel foot proteins (mfps) but also their molecular weight and molecular structure. The large number of catechol and amine groups set the basis for heteromultivalent anchoring and crosslinking. The molecular weight reaches 10 kDa, which is similar to the most adhesive mussel foot protein mfp-5. Also, the dendritic structure exposes its functional groups on the surface like the folded proteins. As a result, a very stable coating can be prepared on virtually any type of material surface within 10 min by a simple dip-coating method, which is as fast as the formation of mussel byssal threads in nature. PMID:25200129

  1. Dendritic Cell Apoptosis and the Pathogenesis of Dengue

    Directory of Open Access Journals (Sweden)

    Lysangela R. Alves

    2012-11-01

    Full Text Available Dengue viruses and other members of the Flaviviridae family are emerging human pathogens. Dengue is transmitted to humans by Aedes aegypti female mosquitoes. Following infection through the bite, cells of the hematopoietic lineage, like dendritic cells, are the first targets of dengue virus infection. Dendritic cells (DCs are key antigen presenting cells, sensing pathogens, processing and presenting the antigens to T lymphocytes, and triggering an adaptive immune response. Infection of DCs by dengue virus may induce apoptosis, impairing their ability to present antigens to T cells, and thereby contributing to dengue pathogenesis. This review focuses on general mechanisms by which dengue virus triggers apoptosis, and possible influence of DC-apoptosis on dengue disease severity.

  2. Dendritic Growth with Fluid Flow for Pure Materials

    Science.gov (United States)

    Jeong, Jun-Ho; Dantzig, Jonathan A.; Goldenfeld, Nigel

    2003-01-01

    We have developed a three-dimensional, adaptive, parallel finite element code to examine solidification of pure materials under conditions of forced flow. We have examined the effect of undercooling, surface tension anisotropy and imposed flow velocity on the growth. The flow significantly alters the growth process, producing dendrites that grow faster, and with greater tip curvature, into the flow. The selection constant decreases slightly with flow velocity in our calculations. The results of the calculations agree well with the transport solution of Saville and Beaghton at high undercooling and high anisotropy. At low undercooling, significant deviations are found. We attribute this difference to the influence of other parts of the dendrite, removed from the tip, on the flow field.

  3. Therapeutic dendritic-cell vaccine for simian AIDS

    Institute of Scientific and Technical Information of China (English)

    Lu,W; Wu,XX; Lu,YZ; Guo,WZ; Andrieu,JM

    2005-01-01

    An effective immune response against human immunodeficiency virus or simian immunodeficiency virus (SIV) is critical in achieving control of viral replication. Here, we show in SIV-infected rhesus monkeys that an effective and durable SIV-specific cellular and humoral immunity is elicited by a vaccination with chemically inactivated SIV-pulsed dendritic cells. After three immunizations made at two-week intervals, the animals exhibited a 50-fold decrease of SIV DNA and a 1,000-fold decrease of SIV RNA in peripheral blood. Such reduced viral load levels were maintained over the remaining 34 weeks of the study. Molecular and cellular analyses of axillary and inguinal node lymphocytes of vaccinated monkeys revealed a correlation between decreased SIV DNA and RNA levels and increased SIV-specific T-cell responses. Neutralizing antibody responses were augmented and remained elevated. Inactivated whole virus-pulsed dendritic cell vaccines are promising means to control diseases caused by immunodeficiency viruses.

  4. Two cases of extranodal follicular dendritic cell sarcoma

    Institute of Scientific and Technical Information of China (English)

    王坚; 孔蕴仪; 陆洪芬; 许越香

    2003-01-01

    @@ Follicular dendritic cell (FDC) is an essential component of the nonlymphoid, nonphagocytic immunoaccessory reticulum cells of the peripheral lymphoid tissue.1 Follicular dendritic cell sarcoma (FDCs) are confined largely to the primary and secondary B-cell follicles, where they form a tight interlacing meshwork. They play a role in the capture and presentation of antigens, generation and regulation of immune complexes. FDCs can be recognized morphologically by their indistinct cellular borders, pale eosinophilic cytoplasm, round-to-ovoid nuclei with delicate nuclear membranes and clear-to-vesicular chromatin with inconspicuous or small nucleoli. FDCs are best identified through immunostaining using CD21, CD35, R4/23, KiM4, KiM4p and Ki-FDC1p.

  5. Disruptive Intelligence : How to gather Information to deal with disruptive innovations

    NARCIS (Netherlands)

    Vriens, D.J.; Solberg Søilen, K.

    2014-01-01

    Disruptive innovations are innovations that have the capacity to transform a whole business into one with products that are more accessible and affordable (cf. Christensen et al. 2009). As Christensen et al. argue no business is immune to such disruptive innovations. If these authors are right, it m

  6. Dendritic cells in asthma: a function beyond sensitization

    OpenAIRE

    Rijt, Leonie

    2004-01-01

    textabstractThe aim of this thesis is to characterize the involvement of dendritic cells in the induction and maintenance of the secondary immune response leading to an eosinophilic airway inflammation as seen in asthma. Special attention was attributed to the mechanisms by which these cells accumulate in the airways of challenged mice, to their interaction with primed CD4+ T cells as well as to their functional contribution to primed T cell activation. These questions were addressed in a wel...

  7. Estimating neuronal connectivity from axonal and dendritic density fields

    Directory of Open Access Journals (Sweden)

    Jaap evan Pelt

    2013-11-01

    Full Text Available Neurons innervate space by extending axonal and dendritic arborizations. When axons and dendrites come in close proximity of each other, synapses between neurons can be formed. Neurons vary greatly in their morphologies and synaptic connections with other neurons. The size and shape of the arborizations determine the way neurons innervate space. A neuron may therefore be characterized by the spatial distribution of its axonal and dendritic 'mass'. A population mean 'mass' density field of a particular neuron type can be obtained by averaging over the individual variations in neuron geometries. Connectivity in terms of candidate synaptic contacts between neurons can be determined directly on the basis of their arborizations but also indirectly on the basis of their density fields. To decide when a candidate synapse can be formed, we previously developed a criterion defining that axonal and dendritic line pieces should cross in 3D and have an orthogonal distance less than a threshold value. In this paper, we developed new methodology for applying this criterion to density fields. We show that estimates of the number of contacts between neuron pairs calculated from their density fields are fully consistent with the number of contacts calculated from the actual arborizations. However, the estimation of the connection probability and the expected number of contacts per connection cannot be calculated directly from density fields, because density fields do not carry anymore the correlative structure in the spatial distribution of synaptic contacts. Alternatively, these two connectivity measures can be estimated from the expected number of contacts by using empirical mapping functions. The neurons used for the validation studies were generated by our neuron simulator NETMORPH. An example is given of the estimation of average connectivity and Euclidean pre- and postsynaptic distance distributions in a network of neurons represented by their population

  8. The influence of infectious factors on dendritic cell apoptosis

    OpenAIRE

    Kubicka-Sierszen, Agata; Grzegorczyk, Janina Ł.

    2015-01-01

    Pathogens can have a negative influence on dendritic cells (DCs), causing their apoptosis, which prevents active presentation of foreign antigens. It results in a state of immunosuppression which makes the body susceptible to secondary infections. Infected immature DCs have lower expression of co-stimulatory and adhesion molecules, reduced ability to secrete cytokines and an inhibited maturation process and are incapable of effective antigen presentation and activation of T-lymphocytes. In so...

  9. [Dendritic cells and interaction with other cell types. Immune tolerance].

    Science.gov (United States)

    Guerder, S

    2001-07-01

    T cell tolerance to self antigen is mainly established in the thymus were self-reactive T cells are deleted. Interdigitating dendritic cells and medulary epithelial cells are directly involved in the deletion process. Some self-reactive T cells escape, however this thymic censorship and enter the peripheral pool of naive T cells. Multiple mechanisms are also at play in the periphery to control this potentially armfull T cells, this include deletion and immune deviation.

  10. Follicular Dendritic Cells Emerge from Ubiquitous Perivascular Precursors

    OpenAIRE

    Krautler, Nike Julia; Kana, Veronika; Kranich, Jan; Tian, Yinghua; Perera, Dushan; Lemm, Doreen; Schwarz, Petra; Armulik, Annika; Browning, Jeffrey L.; Tallquist, Michelle; Buch, Thorsten; Oliveira-Martins, José B.; Zhu, Caihong; Hermann, Mario; Wagner, Ulrich

    2012-01-01

    The differentiation of follicular dendritic cells (FDC) is essential to the remarkable microanatomic plasticity of lymphoid follicles. Here we show that FDC arise from ubiquitous perivascular precursors (preFDC) expressing platelet-derived growth factor receptor β (PDGFRβ). PDGFRβ-Cre-driven reporter gene recombination resulted in FDC labeling, whereas conditional ablation of PDGFRβ+-derived cells abolished FDC, indicating that FDC originate from PDGFRβ+ cells. Lymphotoxin-α-overexpressing pr...

  11. Follicular Dendritic Cells and Dissemination of Creutzfeldt-Jakob Disease

    OpenAIRE

    Manuelidis, Laura; Zaitsev, Igor; Koni, Pandelakis; Yun Lu, Zhi; Richard A Flavell; Fritch, William

    2000-01-01

    The contribution of immune system cells to the propagation of transmissible encephalopathies is not well understood. To determine how follicular dendritic cells (FDC) may act, we challenged lymphotoxin β null and wild-type (wt) controls with a Creutzfeldt-Jakob disease (CJD) agent. There was only a small difference in incubation time to clinical disease even after peripheral challenge with low infectious doses (31 in a total of 410 days). Brain pathology with extensive microglial infiltration...

  12. Dendritic spine shape analysis using disjunctive normal shape models

    OpenAIRE

    Ghani, Muhammad Usman; Mesadi, Fitsum; Demir Kanık, Sümerya Ümmühan; Demir Kanik, Sumerya Ummuhan; Argunşah, Ali Özgür; Argunsah, Ali Ozgur; Israely, Inbal; Ünay, Devrim; Unay, Devrim; Taşdizen, Tolga; Tasdizen, Tolga; Çetin, Müjdat; Cetin, Mujdat

    2016-01-01

    Analysis of dendritic spines is an essential task to understand the functional behavior of neurons. Their shape variations are known to be closely linked with neuronal activities. Spine shape analysis in particular, can assist neuroscientists to identify this relationship. A novel shape representation has been proposed recently, called Disjunctive Normal Shape Models (DNSM). DNSM is a parametric shape representation and has proven to be successful in several segmentation problems. In this pap...

  13. On comparison of manifold learning techniques for dendritic spine classification

    OpenAIRE

    Ghani, Muhammad Usman; Argunşah, Ali Özgür; Argunsah, Ali Ozgur; Israely, Inbal; Ünay, Devrim; Unay, Devrim; Taşdizen, Tolga; Tasdizen, Tolga; Çetin, Müjdat; Cetin, Mujdat

    2016-01-01

    Dendritic spines are one of the key functional components of neurons. Their morphological changes are correlated with neuronal activity. Neuroscientists study spine shape variations to understand their relation with neuronal activity. Currently this analysis performed manually, the availability of reliable automated tools would assist neuroscientists and accelerate this research. Previously, morphological features based spine analysis has been performed and reported in the literature. In this...

  14. Redefining the role of dendritic cells in periodontics

    OpenAIRE

    Gomathinayagam Venkatesan; Ashita Uppoor; Naik, Dilip G.

    2013-01-01

    A properly functioning adaptive immune system signifies the best features of life. It is diverse beyond compare, tolerant without fail, and capable of behaving appropriately with a myriad of infections and other challenges. Dendritic cells (DCs) are required to explain how this remarkable system is energized and directed. DCs consist of a family of antigen presenting cells, which are bone-marrow-derived cells that patrol all tissues of the body with the possible exceptions of the brain and te...

  15. Signal Propagation in Oblique Dendrites of CA1 Pyramidal Cells

    OpenAIRE

    Migliore, Michele; Ferrante, Michele; Ascoli, Giorgio A.

    2005-01-01

    The electrophysiological properties of the oblique branches of CA1 pyramidal neurons are largely unknown and very difficult to investigate experimentally. These relatively thin dendrites make up the majority of the apical tree surface area and constitute the main target of Schaffer collateral axons from CA3. Their electrogenic properties might have an important role in defining the computational functions of CA1 neurons. It is thus important to determine if and to what extent the back- and fo...

  16. Oral acyclovir (Zovirax) in herpes simplex dendritic corneal ulceration.

    OpenAIRE

    Collum, L M; McGettrick, P.; Akhtar, J.; Lavin, J.; Rees, P J

    1986-01-01

    Sixty patients with simple dendritic corneal ulceration were randomly assigned to double blind treatment with either acyclovir tablets (400 mg) or acyclovir ophthalmic ointment administered five times daily. There was no significant difference in the proportions of patients healed in either treatment group (88.9% on oral acyclovir and 96.6% on acyclovir ointment). The median healing time was five days in both groups. No systemic or significant local side effects were noted in either treatment...

  17. Receptor-Dependent Coronavirus Infection of Dendritic Cells

    Science.gov (United States)

    Turner, Brian C.; Hemmila, Erin M.; Beauchemin, Nicole; Holmes, Kathryn V.

    2004-01-01

    In several mammalian species, including humans, coronavirus infection can modulate the host immune response. We show a potential role of dendritic cells (DC) in murine coronavirus-induced immune modulation and pathogenesis by demonstrating that the JAW SII DC line and primary DC from BALB/c mice and p/p mice with reduced expression of the murine coronavirus receptor, murine CEACAM1a, are susceptible to murine coronavirus infection by a receptor-dependent pathway. PMID:15113927

  18. Dendritic Cell Responses to Surface Properties of Clinical Titanium Surfaces

    OpenAIRE

    Kou, Peng Meng; Schwartz, Zvi; Boyan, Barbara D; Babensee, Julia E.

    2010-01-01

    Dendritic cells (DCs) play pivotal roles in responding to foreign entities during an innate immune response and initiating effective adaptive immunity as well as maintaining immune tolerance. The sensitivity of DCs to foreign stimuli also makes them useful cells to assess the inflammatory response to biomaterials. Elucidating the material property-DC phenotype relationships using a well-defined biomaterial system is expected to provide criteria for immuno-modulatory biomaterial design. Clinic...

  19. Functionalized Carbosilane Dendritic Species as Soluble Support in Organic Synthesis

    NARCIS (Netherlands)

    Koten, G. van; Hovestad, N.J.; Ford, A.; Jastrzebski, J.T.B.H.

    2000-01-01

    A new methodology, which is compatible with the use of reactive organometallic reagents, has been developed for the use of carbosilane dendrimers as soluble supports in organic synthesis. Hydroxy-functionalized dendritic carbosilanes Si[CH2CH2CH2SiMe2(C6H4CH(R)OH)]4 (G0-OH, R = H or (S)-Me) and Si[C

  20. Dendritic cell-based in vitro assays for vaccine immunogenicity

    OpenAIRE

    Vandebriel, Rob J.; Hoefnagel, Marcel H. N.

    2012-01-01

    Dendritic cells (DC) are pivotal in the induction of adaptive immune responses because they can activate naive T-cells. Moreover, they steer these adaptive immune responses by integrating various stimuli, such as from different pathogen associated molecular patterns and the cytokine milieu. Immature DC are very well capable of ingesting protein antigens, whereas mature DC are efficient presenters of peptides to naive T cells. Human DC can be readily cultured from peripheral blood mononuclear ...

  1. Asymptotic parameterization in inverse limit spaces of dendrites

    OpenAIRE

    Hamilton, Brent

    2012-01-01

    In this paper, we study asymptotic behavior arising in inverse limit spaces of dendrites. In particular, the inverse limit is constructed with a single unimodal bonding map, for which points have unique itineraries and the critical point is periodic. Using symbolic dynamics, sufficient conditions for two rays in the inverse limit space to have asymptotic parameterizations are given. Being a topological invariant, the classification of asymptotic parameterizations would be a useful tool when d...

  2. A dendritic disinhibitory circuit mechanism for pathway-specific gating

    Science.gov (United States)

    Yang, Guangyu Robert; Murray, John D.; Wang, Xiao-Jing

    2016-01-01

    While reading a book in a noisy café, how does your brain ‘gate in' visual information while filtering out auditory stimuli? Here we propose a mechanism for such flexible routing of information flow in a complex brain network (pathway-specific gating), tested using a network model of pyramidal neurons and three classes of interneurons with connection probabilities constrained by data. We find that if inputs from different pathways cluster on a pyramidal neuron dendrite, a pathway can be gated-on by a disinhibitory circuit motif. The branch-specific disinhibition can be achieved despite dense interneuronal connectivity, even with random connections. Moreover, clustering of input pathways on dendrites can naturally emerge through synaptic plasticity regulated by dendritic inhibition. This gating mechanism in a neural circuit is further demonstrated by performing a context-dependent decision-making task. The model suggests that cognitive flexibility engages top-down signalling of behavioural rule or context that targets specific classes of inhibitory neurons. PMID:27649374

  3. The Current Immune Function of Hepatic Dendritic Cells

    Institute of Scientific and Technical Information of China (English)

    Willy Hsu; Shang-An Shu; Eric Gershwin; Zhe-Xiong Lian

    2007-01-01

    While only a small percentage of the liver as dendritic cells, they play a major role in the regulation of liver immunity. Four major types of dendritic cell subsets include myeloid CD8α-B220-, lymphoid CD8α+B220-,plasmacytoid CD8α-B220+, and natural killer dendritic cell with CD8α-B220-NK1.1+ phenotype. Although these subsets have slightly different characteristics, they are all poor na(i)ve T cell stimulators. In exchange for their reduced capacity for allostimulation, hepatic DCs are equipped with an enhanced ability to secrete cytokines in response to TLR stimulation. In addition, they have increased level of phagocytosis. Both of these traits suggest hepatic DC as part of the innate immune system. With such a high rate of exposure to the dietary and commensal antigens, it is important for the hepatic DCs to have an enhanced innate response while maintaining a tolerogenic state to avoid chronic inflammation. Only upon secondary infectivity does the hepatic DC activate memory T cells for rapid eradication of recurring pathogen. On the other hand, overly tolerogenic characteristics of hepatic DC may be responsible for the increase prevalence of autoimmunity or liver malignancies.

  4. Dextromethorphan inhibits activations and functions in dendritic cells.

    Science.gov (United States)

    Chen, Der-Yuan; Song, Pei-Shan; Hong, Jau-Shyong; Chu, Ching-Liang; Pan, I-Horng; Chen, Yi-Ming; Lin, Ching-Hsiung; Lin, Sheng-Hao; Lin, Chi-Chen

    2013-01-01

    Dendritic cells (DCs) play an important role in connecting innate and adaptive immunity. Thus, DCs have been regarded as a major target for the development of immunomodulators. In this study, we examined the effect of dextromethorphan (DXM), a common cough suppressant with a high safety profile, on the activation and function of DCs. In the presence of DXM, the LPS-induced expression of the costimulatory molecules in murine bone marrow-derived dendritic cells (BMDCs) was significantly suppressed. In addition, DXM treatment reduced the production of reactive oxygen species (ROS), proinflammatory cytokines, and chemokines in maturing BMDCs that were activated by LPS. Therefore, DXM abrogated the ability of LPS-stimulated DCs to induce Ag-specific T-cell activation, as determined by their decreased proliferation and IFN- γ secretion in mixed leukocyte cultures. Moreover, the inhibition of LPS-induced MAPK activation and NF- κ B translocation may contribute to the suppressive effect of DXM on BMDCs. Remarkably, DXM decreased the LPS-induced surface expression of CD80, CD83, and HLA-DR and the secretion of IL-6 and IL-12 in human monocyte-derived dendritic cells (MDDCs). These findings provide a new insight into the impact of DXM treatment on DCs and suggest that DXM has the potential to be used in treating DC-related acute and chronic diseases. PMID:23781253

  5. Dextromethorphan Inhibits Activations and Functions in Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Der-Yuan Chen

    2013-01-01

    Full Text Available Dendritic cells (DCs play an important role in connecting innate and adaptive immunity. Thus, DCs have been regarded as a major target for the development of immunomodulators. In this study, we examined the effect of dextromethorphan (DXM, a common cough suppressant with a high safety profile, on the activation and function of DCs. In the presence of DXM, the LPS-induced expression of the costimulatory molecules in murine bone marrow-derived dendritic cells (BMDCs was significantly suppressed. In addition, DXM treatment reduced the production of reactive oxygen species (ROS, proinflammatory cytokines, and chemokines in maturing BMDCs that were activated by LPS. Therefore, DXM abrogated the ability of LPS-stimulated DCs to induce Ag-specific T-cell activation, as determined by their decreased proliferation and IFN-γ secretion in mixed leukocyte cultures. Moreover, the inhibition of LPS-induced MAPK activation and NF-κB translocation may contribute to the suppressive effect of DXM on BMDCs. Remarkably, DXM decreased the LPS-induced surface expression of CD80, CD83, and HLA-DR and the secretion of IL-6 and IL-12 in human monocyte-derived dendritic cells (MDDCs. These findings provide a new insight into the impact of DXM treatment on DCs and suggest that DXM has the potential to be used in treating DC-related acute and chronic diseases.

  6. Containerless Undercooled Melts: Ordering, Nucleation, and Dendrite Growth

    Science.gov (United States)

    Herlach, Dieter M.; Binder, Sven; Galenko, Peter; Gegner, Jan; Holland-Moritz, Dirk; Klein, Stefan; Kolbe, Matthias; Volkmann, Thomas

    2015-11-01

    Electromagnetic and electrostatic levitation are applied to containerless undercool and solidify metallic melts. A large undercooling range becomes accessible with the extra benefit that the freely suspended drop is accessible directly for in situ observation. The short-range order in undercooled melts is investigated by combining levitation with elastic neutron scattering and X-ray scattering using synchrotron radiation. Muon Spin Rotation ( µSR) experiments show magnetic ordering in deeply undercooled Co80Pd20 alloys. The onset of magnetic ordering stimulates nucleation. Results on nucleation undercooling of zirconium are presented showing the limit of maximum undercoolability set by the onset of homogeneous nucleation. Metastable phase diagrams are determined by applying energy-dispersive X-ray diffraction of Ni-V alloys with varying concentration. Nucleation is followed by crystal growth. Rapid dendrite growth velocity is measured on levitation-processed samples as a function of undercooling ∆ T by using high-speed video camera technique. Solute trapping in dilute solid solutions and disorder trapping in intermetallic compounds are experimentally verified. Measurements of glass-forming Cu-Zr alloy show a maximum in the V(∆ T) relation that is indicative for diffusion-controlled growth. The influence of convection on dendrite growth of Al50Ni50 is shown by comparative measurements of dendrite growth velocity on Earth and in reduced gravity. Eventually, faceting of a rough interface by convection is presented as observed on Ni2B alloys.

  7. Dendrite Suppression by Shock Electrodeposition in Charged Porous Media

    Science.gov (United States)

    Han, Ji-Hyung; Wang, Miao; Bai, Peng; Brushett, Fikile R.; Bazant, Martin Z.

    2016-06-01

    It is shown that surface conduction can stabilize electrodeposition in random, charged porous media at high rates, above the diffusion-limited current. After linear sweep voltammetry and impedance spectroscopy, copper electrodeposits are visualized by scanning electron microscopy and energy dispersive spectroscopy in two different porous separators (cellulose nitrate, polyethylene), whose surfaces are modified by layer-by-layer deposition of positive or negative charged polyelectrolytes. Above the limiting current, surface conduction inhibits growth in the positive separators and produces irregular dendrites, while it enhances growth and suppresses dendrites behind a deionization shock in the negative separators, also leading to improved cycle life. The discovery of stable uniform growth in the random media differs from the non-uniform growth observed in parallel nanopores and cannot be explained by classic quasi-steady “leaky membrane” models, which always predict instability and dendritic growth. Instead, the experimental results suggest that transient electro-diffusion in random porous media imparts the stability of a deionization shock to the growing metal interface behind it. Shock electrodeposition could be exploited to enhance the cycle life and recharging rate of metal batteries or to accelerate the fabrication of metal matrix composite coatings.

  8. Overview of the Tusas Code for Simulation of Dendritic Solidification

    Energy Technology Data Exchange (ETDEWEB)

    Trainer, Amelia J. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Newman, Christopher Kyle [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Francois, Marianne M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-01-07

    The aim of this project is to conduct a parametric investigation into the modeling of two dimensional dendrite solidification, using the phase field model. Specifically, we use the Tusas code, which is for coupled heat and phase-field simulation of dendritic solidification. Dendritic solidification, which may occur in the presence of an unstable solidification interface, results in treelike microstructures that often grow perpendicular to the rest of the growth front. The interface may become unstable if the enthalpy of the solid material is less than that of the liquid material, or if the solute is less soluble in solid than it is in liquid, potentially causing a partition [1]. A key motivation behind this research is that a broadened understanding of phase-field formulation and microstructural developments can be utilized for macroscopic simulations of phase change. This may be directly implemented as a part of the Telluride project at Los Alamos National Laboratory (LANL), through which a computational additive manufacturing simulation tool is being developed, ultimately to become part of the Advanced Simulation and Computing Program within the U.S. Department of Energy [2].

  9. Barriers in the Brain: Resolving Dendritic Spine Morphology and Compartmentalization

    Directory of Open Access Journals (Sweden)

    Max eAdrian

    2014-12-01

    Full Text Available Dendritic spines are micron-sized protrusions that harbor the majority of excitatory synapses in the central nervous system. The head of the spine is connected to the dendritic shaft by a 50-400 nm thin membrane tube, called the spine neck, which has been hypothesized to confine biochemical and electric signals within the spine compartment. Such compartmentalization could minimize interspinal crosstalk and thereby support spine-specific synapse plasticity. However, to what extent compartmentalization is governed by spine morphology, and in particular the diameter of the spine neck, has remained unresolved. Here, we review recent advances in tool development - both experimental and theoretical - that facilitate studying the role of the spine neck in compartmentalization. Special emphasis is given to recent advances in microscopy methods and quantitative modeling applications as we discuss compartmentalization of biochemical signals, membrane receptors and electrical signals in spines. Multidisciplinary approaches should help to answer how dendritic spine architecture affects the cellular and molecular processes required for synapse maintenance and modulation.

  10. A dendritic disinhibitory circuit mechanism for pathway-specific gating.

    Science.gov (United States)

    Yang, Guangyu Robert; Murray, John D; Wang, Xiao-Jing

    2016-01-01

    While reading a book in a noisy café, how does your brain 'gate in' visual information while filtering out auditory stimuli? Here we propose a mechanism for such flexible routing of information flow in a complex brain network (pathway-specific gating), tested using a network model of pyramidal neurons and three classes of interneurons with connection probabilities constrained by data. We find that if inputs from different pathways cluster on a pyramidal neuron dendrite, a pathway can be gated-on by a disinhibitory circuit motif. The branch-specific disinhibition can be achieved despite dense interneuronal connectivity, even with random connections. Moreover, clustering of input pathways on dendrites can naturally emerge through synaptic plasticity regulated by dendritic inhibition. This gating mechanism in a neural circuit is further demonstrated by performing a context-dependent decision-making task. The model suggests that cognitive flexibility engages top-down signalling of behavioural rule or context that targets specific classes of inhibitory neurons. PMID:27649374

  11. Mechanical algal disruption for efficient biodiesel extraction

    Science.gov (United States)

    Krehbiel, Joel David

    Biodiesel from algae provides several benefits over current biodiesel feedstocks, but the energy requirements of processing algae into a useable fuel are currently so high as to be prohibitive. One route to improving this is via disruption of the cells prior to lipid extraction, which can significantly increase energy recovery. Unfortunately, several obvious disruption techniques require more energy than can be gained. This dissertation examines the use of microbubbles to improve mechanical disruption of algal cells using experimental, theoretical, and computational methods. New laboratory experiments show that effective ultrasonic disruption of algae is achieved by adding microbubbles to an algal solution. The configuration studied flows the solution through a tube and insonifies a small section with a high-pressure ultrasound wave. Previous biomedical research has shown effective cell membrane damage on animal cells with similar methods, but the present research is the first to extend such study to algal cells. Results indicate that disruption increases with peak negative pressure between 1.90 and 3.07 MPa and with microbubble concentration up to 12.5 x 107 bubbles/ml. Energy estimates of this process suggest that it requires only one-fourth the currently most-efficient laboratory-scale disruption process. Estimates of the radius near each bubble that causes disruption (i.e. the disruption radius) suggest that it increases with peak negative pressure and is near 9--20 microm for all cases tested. It is anticipated that these procedures can be designed for better efficiency and efficacy, which will be facilitated by identifying the root mechanisms of the bubble-induced disruption. We therefore examine whether bubble expansion alone creates sufficient cell deformation for cell rupture. The spherically-symmetric Marmottant model for bubble dynamics allows estimation of the flow regime under experimental conditions. Bubble expansion is modeled as a point source of

  12. Disc formation from stellar tidal disruptions

    CERN Document Server

    Bonnerot, Clément; Lodato, Giuseppe; Price, Daniel J

    2015-01-01

    The potential of tidal disruption of stars to probe otherwise quiescent supermassive black holes cannot be exploited, if their dynamics is not fully understood. So far, the observational appearance of these events has been commonly derived from analytical extrapolations of the debris dynamical properties just after the stellar disruption. In this paper, we perform hydrodynamical simulations of stars in highly eccentric orbits, that follow the stellar debris after disruption and investigate their ultimate fate. We demonstrate that gas debris circularize on an orbital timescale because relativistic apsidal precession causes the stream to self-cross. The higher the eccentricity and/or the deeper the encounter, the faster is the circularization. If the internal energy deposited by shocks during stream self-interaction is readily radiated, the gas forms a narrow ring at the circularization radius. It will then proceed to accrete viscously at a super-Eddington rate, puffing up under radiation pressure. If instead c...

  13. Mermaid syndrome with amniotic band disruption.

    Science.gov (United States)

    Managoli, Sanjeev; Chaturvedi, Pushpa; Vilhekar, Krishna Y; Iyenger, Janaki

    2003-01-01

    An association of Amniotic Band Disruption Sequence and Mermaid Syndrome in a newborn having multiple congenital anomalies is being reported. The newborn had aberrant string like tissues attached to the amputed fingers and toes. Adhesions of amniotic bands had disrupted the fetal parts especially anteriorly in the midline, causing multiple anomalies. Apart from these features of Amniotic Band Disruption Sequence, the newborn had complete fusion of the lower limbs by cutaneous tissue, a characteristic of Mermaid Syndrome (Sirenomelia). Associated malformations were anal stenosis, rectal atresia, small horseshoe kidney, hypoplastic urinary bladder and a bicomuate uterus. The single umbilical artery had a high origin, arising directly from the aorta just distal to the celiac axis, which is unique to sirenomelia. Theories put forward regarding the etiopathogenesis of both the conditions are discussed. PMID:12619964

  14. Disruption, beamstrahlung, and beamstrahlung pair creation

    Energy Technology Data Exchange (ETDEWEB)

    Chen, P.

    1988-12-01

    The two major effects from the interaction of e/sup /minus//e/sup +/ beams---beamstrahlung and disruption---are reviewed, with emphasis on flat beam collisions. For the disruption effects we discuss the luminosity enhancement factor, the maximum and rms disruption angles, and the ''kink instability''. All the results are obtained from computer simulations, and scaling laws based on these are deduced whenever possible. For the beamstrahlung effects, we concentrate only on the final electron energy spectrum and the deflection angle associated with low energy particles. In addition to the generic studies on the beam-beam effects, we also list the relevant beam-beam parameters obtained from simulations on two sample designs: the TLC and the ILC. As an addendum, the newly discovered phenomenon of coherent beamstrahlung pair creation, together with the incoherent process, are discussed. 18 refs., 15 figs., 1 tab.

  15. Effect of cooling rates on dendrite spacings of directionally solidified DZ125 alloy under high thermal gradient

    Institute of Scientific and Technical Information of China (English)

    ZHANG Weiguo; LIU Lin; ZHAO Xinbao; HUANG Taiwen; YU Zhuhuan; QU Min; FU Hengzhi

    2009-01-01

    The dendrite morphologies and spacings of directionally solidified DZ125 superalloy were investigated under high thermal gradient about 500 K/cm. The results reveal that, with increasing cooling rate, both the spacings of primary and secondary dendrite arms decrease, and the dendrite morphologies transit from coarse to superfine dendrite. The secondary dendrite arms trend to be refined and be well developed, and the tertiary dendrite will occur. The predictions of the Kurz/Fisher model and the Hunt/Lu model accord basically with the experimental data for primary dendrite arm spacing. The regression equation of the primary dendrite arm spacings λ_1 and the cooling rate V_c is λ_1=0.013V_c~(-0.32). The regression equation of the secondary dendrite arm spacing λ_2 and the cooling rate V_c is λ_2=0.00258V_c~(-0.31), which gives good agreement with the Feurer/Wunderlin model.

  16. Skin-derived cues control arborization of sensory dendrites in Caenorhabditis elegans.

    Science.gov (United States)

    Salzberg, Yehuda; Díaz-Balzac, Carlos A; Ramirez-Suarez, Nelson J; Attreed, Matthew; Tecle, Eillen; Desbois, Muriel; Kaprielian, Zaven; Bülow, Hannes E

    2013-10-10

    Sensory dendrites depend on cues from their environment to pattern their growth and direct them toward their correct target tissues. Yet, little is known about dendrite-substrate interactions during dendrite morphogenesis. Here, we describe MNR-1/menorin, which is part of the conserved Fam151 family of proteins and is expressed in the skin to control the elaboration of "menorah"-like dendrites of mechanosensory neurons in Caenorhabditis elegans. We provide biochemical and genetic evidence that MNR-1 acts as a contact-dependent or short-range cue in concert with the neural cell adhesion molecule SAX-7/L1CAM in the skin and through the neuronal leucine-rich repeat transmembrane receptor DMA-1 on sensory dendrites. Our data describe an unknown pathway that provides spatial information from the skin substrate to pattern sensory dendrite development nonautonomously. PMID:24120132

  17. Statistical physics of neural systems with non-additive dendritic coupling

    CERN Document Server

    Breuer, David; Memmesheimer, Raoul-Martin

    2015-01-01

    How neurons process their inputs crucially determines the dynamics of biological and artificial neural networks. In such neural and neural-like systems, synaptic input is typically considered to be merely transmitted linearly or sublinearly by the dendritic compartments. Yet, single-neuron experiments report pronounced supralinear dendritic summation of sufficiently synchronous and spatially close-by inputs. Here, we provide a statistical physics approach to study the impact of such non-additive dendritic processing on single neuron responses and the performance of associative memory tasks in artificial neural networks. First, we compute the effect of random input to a neuron incorporating nonlinear dendrites. This approach is independent of the details of the neuronal dynamics. Second, we use those results to study the impact of dendritic nonlinearities on the network dynamics in a paradigmatic model for associative memory, both numerically and analytically. We find that dendritic nonlinearities maintain net...

  18. Properties of mouse retinal ganglion cell dendritic growth during postnatal development

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The property of dendritic growth dynamics during development is a subject of intense interest.Here,we investigated the dendritic motility of retinal ganglion cells (RGCs) during different developmental stages,using ex vivo mouse retina explant culture,Semliki Forest Virus transfection and time-lapse observations.The results illustrated that during development,the dendritic motility underwent a change from rapid growth to a relatively stable state,i.e.,at P0 (day of birth),RGC dendrites were in a highly active state,whereas at postnatal 13 (P13) they were more stable,and at P3 and P8,the RGCs were in an intermediate state.At any given developmental stage,RGCs of different types displayed the same dendritic growth rate and extent.Since the mouse is the most popular mammalian model for genetic manipulation,this study provided a methodological foundation for further exploring the regulatory mechanisms of dendritic development.

  19. Morphology of Pyramidal Neurons in the Rat Prefrontal Cortex: Lateralized Dendritic Remodeling by Chronic Stress

    Directory of Open Access Journals (Sweden)

    Claudia Perez-Cruz

    2007-01-01

    Full Text Available The prefrontal cortex (PFC plays an important role in the stress response. We filled pyramidal neurons in PFC layer III with neurobiotin and analyzed dendrites in rats submitted to chronic restraint stress and in controls. In the right prelimbic cortex (PL of controls, apical and distal dendrites were longer than in the left PL. Stress reduced the total length of apical dendrites in right PL and abolished the hemispheric difference. In right infralimbic cortex (IL of controls, proximal apical dendrites were longer than in left IL, and stress eliminated this hemispheric difference. No hemispheric difference was detected in anterior cingulate cortex (ACx of controls, but stress reduced apical dendritic length in left ACx. These data demonstrate interhemispheric differences in the morphology of pyramidal neurons in PL and IL of control rats and selective effects of stress on the right hemisphere. In contrast, stress reduced dendritic length in the left ACx.

  20. Tidal disruption of stars by SMBHs

    Science.gov (United States)

    Komossa, S.

    2016-06-01

    The tidal disruption and subsequent accretion of stars by supermassive black holes produces spectacular flares in the X-ray sky. First found with ROSAT, ongoing and upcoming sky surveys will find these events in the 1000s. In X-rays, tidal disruption events (TDEs) provide us with powerful new probes of accretion physics under extreme conditions, of the formation of disk winds, of relativistic effects near the SMBH, and of the presence of supermassive binary black holes. This talk reviews the status of observations, and discusses future prospects. XMM-Newton will continue to play an important role in identifying new events and carry out spectroscopic follow-ups.

  1. Abundance Anomalies In Tidal Disruption Events

    OpenAIRE

    Kochanek, C. S.

    2015-01-01

    The ~10% of tidal disruption events (TDEs) due to stars more massive than the Sun should show abundance anomalies due to stellar evolution in helium, carbon and nitrogen, but not oxygen. Helium is always enhanced, but only by up to ~25% on average because it becomes inaccessible once it is sequestered in the high density core as the star leaves the main sequence. However, portions of the debris associated with the disrupted core of a main sequence star can be enhanced in helium by factors of ...

  2. Manufacturing doubt about endocrine disrupter science

    DEFF Research Database (Denmark)

    Bergman, Åke; Becher, Georg; Blumberg, Bruce;

    2015-01-01

    We present a detailed response to the critique of "State of the Science of Endocrine Disrupting Chemicals 2012" (UNEP/WHO, 2013) by financial stakeholders, authored by Lamb et al. (2014). Lamb et al.'s claim that UNEP/WHO (2013) does not provide a balanced perspective on endocrine disruption......) report is not particularly erudite and that their critique is not intended to be convincing to the scientific community, but to confuse the scientific data. Consequently, it promotes misinterpretation of the UNEP/WHO (2013) report by non-specialists, bureaucrats, politicians and other decision makers...

  3. Engineering aspects of disruption current decay

    International Nuclear Information System (INIS)

    Engineering features associated with the configuration of a tokamak can affect the amount of energy that produces melting and damage to the limiters or internal wall surfaces as the result of a major disruption. During the current decay period of a major thermal disruption, the energy that can damage a wall or limiter comes from the external magnetic field. By providing a good conducting torus near the plasma and increasing the plasma circuit resistance, this magnetic energy (transferred by way of the plasma circuit) can be minimized. This report addresses engineering design features to reduce the energy deposited on the inner torus surface that produces melting of the structures

  4. Disruptive Innovation by Emerging Multinational Latecomers

    DEFF Research Database (Denmark)

    Li, Peter Ping

    on disruptive innovation (DI) and the bottom of the pyramid (BOP) provides a great opportunity to shed light on the key issue. To take advantage of this “missed” opportunity, I integrate the two reframed constructs of DI and BOP and also develop a typology of four ideal-typical innovations toward a theory...... of latecomer innovation as a special DI by EMNE at BOP to provide insights into the mechanisms underlying the trajectories of catching up and leapfrogging. Built upon latecomer innovation, EMNEs at BOP can emerge as the most disruptive challengers to the MNE incumbents at TOP. The implications of reframed...

  5. Contextual Learning Induces Dendritic Spine Clustering in Retrosplenial Cortex

    Directory of Open Access Journals (Sweden)

    Adam C Frank

    2014-03-01

    Full Text Available Molecular and electrophysiological studies find convergent evidence suggesting that plasticity within a dendritic tree is not randomly dispersed, but rather clustered into functional groups. Further, results from in silico neuronal modeling show that clustered plasticity is able to increase storage capacity 45 times compared to dispersed plasticity. Recent in vivo work utilizing chronic 2-photon microscopy tested the clustering hypothesis and showed that repetitive motor learning is able to induce clustered addition of new dendritic spines on apical dendrites of L5 neurons in primary motor cortex; moreover, clustered spines were found to be more stable than non-clustered spines, suggesting a physiological role for spine clustering. To further test this hypothesis we used in vivo 2-photon imaging in Thy1-YFP-H mice to chronically examine dendritic spine dynamics in retrosplenial cortex (RSC during spatial learning. RSC is a key component of an extended spatial learning and memory circuit that includes hippocampus and entorhinal cortex. Importantly, RSC is known from both lesion and immediate early gene studies to be critically involved in spatial learning and more specifically in contextual fear conditioning. We utilized a modified contextual fear conditioning protocol wherein animals received a mild foot shock each day for five days; this protocol induces gradual increases in context freezing over several days before the animals reach a behavioral plateau. We coupled behavioral training with four separate in vivo imaging sessions, two before training begins, one early in training, and a final session after training is complete. This allowed us to image spine dynamics before training as well as early in learning and after animals had reached behavioral asymptote. We find that this contextual learning protocol induces a statistically significant increase in the formation of clusters of new dendritic spines in trained animals when compared to home

  6. Principles of self-assembly of helical pores from dendritic dipeptides

    Science.gov (United States)

    Percec, Virgil; Dulcey, Andrés E.; Peterca, Mihai; Ilies, Monica; Nummelin, Sami; Sienkowska, Monika J.; Heiney, Paul A.

    2006-01-01

    The self-assembly of the dendritic dipeptides (4-3,4-3,5)nG2-CH2-Boc-l-Tyr-l-Ala-OMe and their achiral dendritic alcohol (4-3,4-3,5)nG2-CH2OH precursors, both with n = 1–16, where n represents the number of methylenic units in the alkyl groups of the dendron, are reported. All chiral dendritic dipeptides and achiral dendritic alcohols self-assemble into helical porous columns that are stable in both solution and solid state. The pore diameter (Dpore) of the columns self-assembled from dendritic dipeptides is ≈10 Å larger than that of structures assembled from dendritic alcohols. The increase of the Dpore at the transition from dendritic alcohol to dendritic dipeptide is accompanied by a decreased solid angle of the building block. This trend is in agreement with previous pore size-solid angle dependences observed with different protective groups of the dipeptide and primary structures of the dendron. However, within the series of dendritic alcohols and dendritic dipeptides with various n, the Dpore increases when the solid angle increases. The results of these investigations together with those of previous studies on the role of dipeptide stereochemistry and protective groups on this self-assembly process provide the molecular principles required to program the construction of supramolecular helical pores with diameter controlled at the Å level from a single dendritic dipeptide architecture. These principles are expected to be valid for libraries of dendritic dipeptides based on dendrons and dipeptides with various primary structures. PMID:16469843

  7. Development of Ag dendrites-reduced graphene oxide composite catalysts via galvanic replacement reaction

    Science.gov (United States)

    Fu, Li; Sokiransky, Mika Matsunaka; Wang, James; Lai, Guosong; Yu, Aimin

    2016-09-01

    Silver dendrites/reduced graphene oxide (AgD/RGO) composites were synthesized via a facile galvanic replacement method. The successful formation of Ag dendrites and the graphene oxide reduction were proved by a series of characterization techniques. The possible formation mechanism of Ag dendrites during the galvanic replacement reaction was discussed. The catalytic activity of the as-synthesized AgD/RGO composite was evaluated by its performance on the chemical reduction of an organic dye methylene blue. The AgD/RGO composite showed a much higher catalytic performance and stability than that of Ag dendrites.

  8. Dendritic calcium activity precedes inspiratory bursts in preBotzinger complex neurons

    DEFF Research Database (Denmark)

    Del Negro, Christopher A; Hayes, John A; Rekling, Jens C

    2011-01-01

    sites 50-300 µm distal from the soma. Preinspiratory Ca(2+) transients occur in hotspots, not ubiquitously, in dendrites. Ca(2+) activity propagates orthodromically toward the soma (and antidromically to more distal regions of the dendrite) at rapid rates (300-700 µm/s). These high propagation rates...... suggest that dendritic Ca(2+) activates an inward current to electrotonically depolarize the soma, rather than propagate as a regenerative Ca(2+) wave. These data provide new evidence that respiratory rhythmogenesis may depend on dendritic burst-generating conductances activated in the context of network...

  9. Rapid dendritic growth of Al-Ge hypoeutectic alloy in a drop tube

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Dendritic growth in Al-45% Ge hypoeutectic alloy has been investigated during free fall in a 3 m drop tube. Calculations indicate that the undercooling obtained for the falling Al-45% Ge droplets ranges from 13 K to 201 K. The maximum undercooling attains 0.27TL. With the increase of undercooling, the primary (Al) phase undergoes a "columnar dendrite to equiaxed dendrite" structural transition. According to the current rapid dendritic growth theory, the growth of primary (Al) phase is always controlled by solute diffusion.

  10. Overexpression of Androgen Receptors in Target Musculature Confers Androgen Sensitivity to Motoneuron Dendrites

    OpenAIRE

    Huguenard, Anna L.; Fernando, Shannon M.; Monks, D. Ashley; Sengelaub, Dale R.

    2010-01-01

    Androgen sensitivity of motoneuron dendrites is conferred indirectly via the enrichment of androgen receptors in the musculature in transgenic rats overexpressing androgen receptors in skeletal muscle.

  11. GPU phase-field lattice Boltzmann simulations of growth and motion of a binary alloy dendrite

    Science.gov (United States)

    Takaki, T.; Rojas, R.; Ohno, M.; Shimokawabe, T.; Aoki, T.

    2015-06-01

    A GPU code has been developed for a phase-field lattice Boltzmann (PFLB) method, which can simulate the dendritic growth with motion of solids in a dilute binary alloy melt. The GPU accelerated PFLB method has been implemented using CUDA C. The equiaxed dendritic growth in a shear flow and settling condition have been simulated by the developed GPU code. It has been confirmed that the PFLB simulations were efficiently accelerated by introducing the GPU computation. The characteristic dendrite morphologies which depend on the melt flow and the motion of the dendrite could also be confirmed by the simulations.

  12. Electroless Growth of Aluminum Dendrites in NaCl-AlCl3 Melts

    DEFF Research Database (Denmark)

    Li, Qingfeng; Hjuler, H.A.; Berg, Rolf W.;

    1989-01-01

    The spontaneous growth of aluminum dendrites after deposition was observed and examined in sodium chloride-aluminumchloride melts. The concentration gradient of AlCl3 in the vicinity of the cathode surface resulting from electrolysisconstitutes a type of concentration cell with aluminum dendrites...... as electrodes. The short-circuit discharge of thecell is found to be the driving force for the growth of aluminum dendrites. Such a concentration gradient is proposed to beone of the causes for dendrite formation in the case of metal deposition....

  13. Control of dendrite growth by a magnetic field during directional solidification

    Science.gov (United States)

    Dai, Yanchao; Du, Dafan; Hou, Long; Gagnoud, Annie; Ren, Zhongming; Fautrelle, Yves; Moreau, Rene; Li, Xi

    2016-04-01

    In this work, the alignment behavior of three kinds of dendrites (Al3Ni, α-Al and Al2Cu dendrites) with a remarkable crystalline anisotropy during directional solidification under an axial magnetic field is studied by the EBSD technology. Experimental results reveal that the magnetic field is capable of tailoring the dendrite alignment during directional solidification. Further, based on the crystalline anisotropy, a method to control the dendrite alignment by adjusting the angle between the magnetic field and the solidification direction is proposed.

  14. State-dependent firing determines intrinsic dendritic Ca2+ signaling in thalamocortical neurons.

    Science.gov (United States)

    Errington, Adam C; Renger, John J; Uebele, Victor N; Crunelli, Vincenzo

    2010-11-01

    Activity-dependent dendritic Ca(2+) signals play a critical role in multiple forms of nonlinear cellular output and plasticity. In thalamocortical neurons, despite the well established spatial separation of sensory and cortical inputs onto proximal and distal dendrites, respectively, little is known about the spatiotemporal dynamics of intrinsic dendritic Ca(2+) signaling during the different state-dependent firing patterns that are characteristic of these neurons. Here we demonstrate that T-type Ca(2+) channels are expressed throughout the entire dendritic tree of rat thalamocortical neurons and that they mediate regenerative propagation of low threshold spikes, typical of, but not exclusive to, sleep states, resulting in global dendritic Ca(2+) influx. In contrast, actively backpropagating action potentials, typical of wakefulness, result in smaller Ca(2+) influxes that can temporally summate to produce dendritic Ca(2+) accumulations that are linearly related to firing frequency but spatially confined to proximal dendritic regions. Furthermore, dendritic Ca(2+) transients evoked by both action potentials and low-threshold spikes are shaped by Ca(2+) uptake by sarcoplasmic/endoplasmic reticulum Ca(2+) ATPases but do not rely on Ca(2+)-induced Ca(2+) release. Our data demonstrate that thalamocortical neurons are endowed with intrinsic dendritic Ca(2+) signaling properties that are spatially and temporally modified in a behavioral state-dependent manner and suggest that backpropagating action potentials faithfully inform proximal sensory but not distal corticothalamic synapses of neuronal output, whereas corticothalamic synapses only "detect" Ca(2+) signals associated with low-threshold spikes.

  15. Dendritic grain growth simulation in weld pool of nickel base alloy

    Institute of Scientific and Technical Information of China (English)

    Zhan Xiaohong; Wei Yanhong; Ma Rui; Dong Zhibo

    2008-01-01

    Dendritic grain growth at the edge of the weld pool is simulated using a stochastic numerical model of cellular automaton algorithm. The grain growth model is established based upon the balance of solute in the solid/liquid interface of the dendrite tip. Considering the complicated nucleation condition and competitive growth, the dendrite morphologies of different nucleation condition are simulated. The simulated results reproduced the dendrite grain evolution process at the edge of the weld pool. It is indicated that the nucleation condition is an important factor influencing the grain morphologies especially the morphologies of secondary and tertiary arms.

  16. Synthesis and Properties of Dendritic Long-Chain Esters as Crude Oil Flow Improver Additives

    Institute of Scientific and Technical Information of China (English)

    Li Cuiqin; Sun Peng; Shi Weiguang; Wang Jun

    2016-01-01

    The efifciencies of 6 kinds of macromolecules with dendritic structure in improving the lfow properties of crude oil were investigated. The dendritic additives were synthesized using low-generation dendritic poly(amidoamine) and alkyl long-chain acrylic esters as starting materials, and their structures were characterized by the Fourier transform infrared spectroscopy, 1H-nuclear magnetic resonance and elemental analysis. The effects on the pour point and rheological properties of crude oil samples were studied. Efifciencies of dendritic long-chain esters were not only inlfuenced by the alky chain length, but also by the generation of dendrimer. The longer the alkyl chain of dendritic long-chain ester was, the better the effect in the reduction of pour point and apparent viscosity was. Efifciencies of 1.5 generation dendritic long-chain ester with 8 branched chains for the reduction of pour point and apparent viscosity were superior to those of 0.5 generation dendritic long-chain ester with 4 branched chains. Under the same conditions, efifciencies of 1.5 generation dendritic eighteen ester were superior to those of other 1.5 generation dendritic long-chain esters for the reduction of pour point and viscosity of crude oil.

  17. State-dependent firing determines intrinsic dendritic Ca2+ signaling in thalamocortical neurons.

    Science.gov (United States)

    Errington, Adam C; Renger, John J; Uebele, Victor N; Crunelli, Vincenzo

    2010-11-01

    Activity-dependent dendritic Ca(2+) signals play a critical role in multiple forms of nonlinear cellular output and plasticity. In thalamocortical neurons, despite the well established spatial separation of sensory and cortical inputs onto proximal and distal dendrites, respectively, little is known about the spatiotemporal dynamics of intrinsic dendritic Ca(2+) signaling during the different state-dependent firing patterns that are characteristic of these neurons. Here we demonstrate that T-type Ca(2+) channels are expressed throughout the entire dendritic tree of rat thalamocortical neurons and that they mediate regenerative propagation of low threshold spikes, typical of, but not exclusive to, sleep states, resulting in global dendritic Ca(2+) influx. In contrast, actively backpropagating action potentials, typical of wakefulness, result in smaller Ca(2+) influxes that can temporally summate to produce dendritic Ca(2+) accumulations that are linearly related to firing frequency but spatially confined to proximal dendritic regions. Furthermore, dendritic Ca(2+) transients evoked by both action potentials and low-threshold spikes are shaped by Ca(2+) uptake by sarcoplasmic/endoplasmic reticulum Ca(2+) ATPases but do not rely on Ca(2+)-induced Ca(2+) release. Our data demonstrate that thalamocortical neurons are endowed with intrinsic dendritic Ca(2+) signaling properties that are spatially and temporally modified in a behavioral state-dependent manner and suggest that backpropagating action potentials faithfully inform proximal sensory but not distal corticothalamic synapses of neuronal output, whereas corticothalamic synapses only "detect" Ca(2+) signals associated with low-threshold spikes. PMID:21048143

  18. Effect of strontium on primary dendrite and eutectic temperature of A357 aluminum alloy

    Directory of Open Access Journals (Sweden)

    Chen Zhongwei

    2010-05-01

    Full Text Available Solidification process of A357 alloy with Sr addition was investigated in this paper. In particular, the effects of strontium and cooling rate on α-Al dendrite and Al-Si eutectic characteristic temperature were characterized by differential thermal analysis (DTA. Sr addition not only modifies the Al-Si eutectic, but also affects the morphology and structure of primary α-Al dendrite. Sr decreases the growth temperature of α-Al dendrite and Al-Si eutectic, and it also affects the dendrite growth mechanism. It has been found that such effect becomes more significant with higher cooling rate.

  19. Phase field modeling of multiple dendrite growth of AI-Si binary alloy under isothermal solidification

    Institute of Scientific and Technical Information of China (English)

    Sun Qiang; Zhang Yutuo; Cui Haixia; Wang Chengzhi

    2008-01-01

    Phase field method offers the prospect of being able to perform realistic numerical experiments on dendrite growth in metallic systems. In this study, the growth process of multiple dendrites in Ai-2-mole-%-Si binary alloy under isothermal solidification was simulated using phase field model. The simulation results showed the impingement of arbitrarily oriented crystals and the competitive growth among the grains during solidification. With the increase of growing time, the grains begin to coalesce and impinge the adjacent grains. When the dendrites start to impinge, the dendrite growth is obviously inhibited.

  20. Molecular signatures of maturing dendritic cells: implications for testing the quality of dendritic cell therapies

    Directory of Open Access Journals (Sweden)

    Wang Ena

    2010-01-01

    Full Text Available Abstract Background Dendritic cells (DCs are often produced by granulocyte-macrophage colony-stimulating factor (GM-CSF and interleukin-4 (IL-4 stimulation of monocytes. To improve the effectiveness of DC adoptive immune cancer therapy, many different agents have been used to mature DCs. We analyzed the kinetics of DC maturation by lipopolysaccharide (LPS and interferon-γ (IFN-γ induction in order to characterize the usefulness of mature DCs (mDCs for immune therapy and to identify biomarkers for assessing the quality of mDCs. Methods Peripheral blood mononuclear cells were collected from 6 healthy subjects by apheresis, monocytes were isolated by elutriation, and immature DCs (iDCs were produced by 3 days of culture with GM-CSF and IL-4. The iDCs were sampled after 4, 8 and 24 hours in culture with LPS and IFN-γ and were then assessed by flow cytometry, ELISA, and global gene and microRNA (miRNA expression analysis. Results After 24 hours of LPS and IFN-γ stimulation, DC surface expression of CD80, CD83, CD86, and HLA Class II antigens were up-regulated. Th1 attractant genes such as CXCL9, CXCL10, CXCL11 and CCL5 were up-regulated during maturation but not Treg attractants such as CCL22 and CXCL12. The expression of classical mDC biomarker genes CD83, CCR7, CCL5, CCL8, SOD2, MT2A, OASL, GBP1 and HES4 were up-regulated throughout maturation while MTIB, MTIE, MTIG, MTIH, GADD45A and LAMP3 were only up-regulated late in maturation. The expression of miR-155 was up-regulated 8-fold in mDCs. Conclusion DCs, matured with LPS and IFN-γ, were characterized by increased levels of Th1 attractants as opposed to Treg attractants and may be particularly effective for adoptive immune cancer therapy.

  1. THYROID HORMONE DISRUPTION: FROM KINETICS TO DYNAMICS.

    Science.gov (United States)

    A wide range of chemicals with diverse structures act as thyroid disrupting chemicals (TDCs). Broadly defined, TDCs are chemicals that alter the structure or function of the thyroid gland, alter regulatory enzymes associated with thyroid hormones (THs), or change circulating or t...

  2. The Relative Ineffectiveness of Criminal Network Disruption

    NARCIS (Netherlands)

    P.A.C. Duijn; V. Kashirin; P.M.A. Sloot

    2014-01-01

    Researchers, policymakers and law enforcement agencies across the globe struggle to find effective strategies to control criminal networks. The effectiveness of disruption strategies is known to depend on both network topology and network resilience. However, as these criminal networks operate in se

  3. The relative ineffectiveness of criminal network disruption.

    Science.gov (United States)

    Duijn, Paul A C; Kashirin, Victor; Sloot, Peter M A

    2014-01-01

    Researchers, policymakers and law enforcement agencies across the globe struggle to find effective strategies to control criminal networks. The effectiveness of disruption strategies is known to depend on both network topology and network resilience. However, as these criminal networks operate in secrecy, data-driven knowledge concerning the effectiveness of different criminal network disruption strategies is very limited. By combining computational modeling and social network analysis with unique criminal network intelligence data from the Dutch Police, we discovered, in contrast to common belief, that criminal networks might even become 'stronger', after targeted attacks. On the other hand increased efficiency within criminal networks decreases its internal security, thus offering opportunities for law enforcement agencies to target these networks more deliberately. Our results emphasize the importance of criminal network interventions at an early stage, before the network gets a chance to (re-)organize to maximum resilience. In the end disruption strategies force criminal networks to become more exposed, which causes successful network disruption to become a long-term effort. PMID:24577374

  4. Collisional and Rotational Disruption of Asteroids

    Science.gov (United States)

    Walsh, Kevin J.; Michel, Patrick; Richardson, Derek C.

    2011-02-01

    Asteroids are leftover pieces from the era of planet formation that help us understand conditions in the early Solar System. Unlike larger planetary bodies that were subject to global thermal modification during and subsequent to their formation, these small bodies have kept at least some unmodified primordial material from the solar nebula. However, the structural properties of asteroids have been modified considerably since their formation. Thus, we can find among them a great variety of physical configurations and dynamical histories. In fact, with only a few possible exceptions, all asteroids have been modified or completely disrupted many times during the age of the Solar System. This picture is supported by data from space mission encounters with asteroids that show much diversity of shape, bulk density, surface morphology, and other features. Moreover, the gravitational attraction of these bodies is so small that some physical processes occur in a manner far removed from our common experience on Earth. Thus, each visit to a small body has generated as many questions as it has answered. In this review we discuss the current state of research into asteroid disruption processes, focusing on collisional and rotational mechanisms. We find that recent advances in modeling catastrophic disruption by collisions have provided important insights into asteroid internal structures and a deeper understanding of asteroid families. Rotational disruption, by tidal encounters or thermal effects, is responsible for altering many smaller asteroids, and is at the origin of many binary asteroids and oddly shaped bodies.

  5. Empathy in Boys with Disruptive Behavior Disorders

    Science.gov (United States)

    de Wied, Minet; Goudena, Paul P.; Matthys, Walter

    2005-01-01

    Background: The present study examined empathy in 8- to 12-year-old clinically referred boys with disruptive behavior disorders (DBD) (n = 25) and age-matched normal controls (n = 24). Method: Situational empathy was assessed by children's emotional and cognitive responses to six empathy-inducing vignettes (displaying sadness, anger or happiness).…

  6. The Relative Ineffectiveness of Criminal Network Disruption

    Science.gov (United States)

    Duijn, Paul A. C.; Kashirin, Victor; Sloot, Peter M. A.

    2014-02-01

    Researchers, policymakers and law enforcement agencies across the globe struggle to find effective strategies to control criminal networks. The effectiveness of disruption strategies is known to depend on both network topology and network resilience. However, as these criminal networks operate in secrecy, data-driven knowledge concerning the effectiveness of different criminal network disruption strategies is very limited. By combining computational modeling and social network analysis with unique criminal network intelligence data from the Dutch Police, we discovered, in contrast to common belief, that criminal networks might even become `stronger', after targeted attacks. On the other hand increased efficiency within criminal networks decreases its internal security, thus offering opportunities for law enforcement agencies to target these networks more deliberately. Our results emphasize the importance of criminal network interventions at an early stage, before the network gets a chance to (re-)organize to maximum resilience. In the end disruption strategies force criminal networks to become more exposed, which causes successful network disruption to become a long-term effort.

  7. Five disruptive technology directions for 5G

    DEFF Research Database (Denmark)

    Boccardi, Federico; W. Heath Jr., Robert; Lozano, Angel;

    2014-01-01

    New research directions will lead to fundamental changes in the design of future fifth generation (5G) cellular networks. This article describes five technologies that could lead to both architectural and component disruptive design changes: device-centric architectures, millimeter wave, massive...

  8. Traffic disruption route Einstein near building 170

    CERN Multimedia

    A Lopez - TS/CE

    2005-01-01

    The TS/CE Group informs you that, for the duration of the work at Building 170, there may be some disruption to traffic on route Einstein in the vicinity of Building 170. The work is due to take place from the 14th to 18th February. For more information, please contact 165029. A. Lopez TS/CE

  9. The disruptive effect of Think Aloud

    DEFF Research Database (Denmark)

    Nielsen, Janni; Yssing, Carsten

    2004-01-01

    Think Aloud (TA), we ask the question: what happens when users are required to verbalise their visual perceptions and interactions? We argue that TA may have a disruptive effect, suggesting that other techniques be considered. With a theoretical distinction between focal and subsidiary awareness...

  10. Heavy Metals Acting as Endocrine Disrupters

    Directory of Open Access Journals (Sweden)

    Bogdan Georgescu

    2011-10-01

    Full Text Available Last years researches focused on several natural and synthetic compounds that may interfere with the major functionsof the endocrine system and were termed endocrine disrupters. Endocrine disrupters are defined as chemicalsubstances with either agonist or antagonist endocrine effects in human and animals. These effects may be achievedby interferences with the biosynthesis or activity of several endogenous hormones. Recently, it was demonstratedthat heavy metals such as cadmium (Cd, arsen (As, mercury (Hg, nickel (Ni, lead (Pb and zinc (Zn may exhibitendocrine-disrupting activity in animal experiments. Emerging evidence of the intimate mechanisms of action ofthese heavy metals is accumulating. It was revealed, for example, that the Zn atom from the Zn fingers of theestrogen receptor can be replaced by several heavy metal molecules such as copper, cobalt, Ni and Cd. By replacingthe Zn atom with Ni or copper, binding of the estrogen receptor to the DNA hormone responsive elements in the cellnucleus is prevented. In both males and females, low-level exposure to Cd interferes with the biological effects ofsteroid hormones in reproductive organs. Arsen has the property to bind to the glucocorticoid receptor thusdisturbing glucocorticoids biological effects. With regard to Hg, this may induce alterations in male and femalefertility, may affect the function of the hypothalamo-pituitary-thyroid axis or the hypothalamo-pituitary-adrenal axis,and disrupt biosynthesis of steroid hormones.

  11. Analysis of recent fuel-disruption experiments

    International Nuclear Information System (INIS)

    Recent USDOE-sponsored DEH, FGR, and TREAT F series fuel-disruption experiments are analyzed with existing analytical models. The experiments are interpreted and the results used to evaluate the models. Calculations are presented using the FRAS3 fission-gas-behavior code and the DiMelfi-Deitrich fuel-response model

  12. Hot Super Earths: disrupted young jupiters?

    CERN Document Server

    Nayakshin, Sergei

    2011-01-01

    Recent {\\em Kepler} observations revealed an unexpected abundance of "hot" Earth-size to Neptune-size planets in the inner $0.02-0.2$ AU from their parent stars. We propose that these smaller planets are the remnants of massive giant planets that migrated inward quicker than they could contract. We show that such disruptions naturally occur in the framework of the Tidal Downsizing hypothesis for planet formation. We find that the characteristic planet-star separation at which such "hot disruptions" occur is $R \\approx 0.03-0.2$ AU. This result is independent of the planet's embryo mass but is dependent on the accretion rate in the disc. At high accretion rates, $\\dot M \\simgt 10^{-6}\\msun$ yr$^{-1}$, the embryo is unable to contract quickly enough and is disrupted. At late times, when the accretion rate drops to $\\dot M \\simlt 10^{-8} \\msun$ yr$^{-1}$, the embryos migrate sufficiently slow to not be disrupted. These "late arrivals" may explain the well known population of hot jupiters. If type I migration reg...

  13. Analysis of recent fuel-disruption experiments

    Energy Technology Data Exchange (ETDEWEB)

    Kramer, J.M.; Kraft, T.E.; DiMelfi, R.J.; Fenske, G.R.; Gruber, E.E.

    1982-01-01

    Recent USDOE-sponsored DEH, FGR, and TREAT F series fuel-disruption experiments are analyzed with existing analytical models. The experiments are interpreted and the results used to evaluate the models. Calculations are presented using the FRAS3 fission-gas-behavior code and the DiMelfi-Deitrich fuel-response model.

  14. Effect of strontium on columnar growth of dendritic α phase in near-eutectic Al-11.6%Si alloys

    Institute of Scientific and Technical Information of China (English)

    廖恒成; 丁毅; 孙国雄

    2004-01-01

    For Al-11.6 % Si alloy, the influence of the addition of Sr on the morphology of the dendrite α phase was investigated, and the characteristic parameters of the dendrite α phase, the primary dendrite spacing and the secondary dendrite arm spacing, were also measured. The addition of strontium promotes the columnar dendrite growth and leads to a decrease of both the primary dendrite spacing and secondary dendrite arm spacing with the increase of the content of strontium in the modified near-eutectic Al-Si alloys. It is thought that the addition of Sr leads to a reduction of the solid-liquid interfacial energy of the dendrite α phase, consequently resulting in a decrease of the growth undercooling of dendrite tips. And hence, the nucleation of the equiaxed grains in the liquid in front of the columnar dendrite tips is restrained, thus the addition of strontium in Al-Si alloys promotes the growth of the columnar dendrites. The reduction of the solid-liquid interfacial energy also leads to the decreases in the primary dendrite spacing and the secondary dendrite arm spacing.

  15. Identification of genes influencing dendrite morphogenesis in developing peripheral sensory and central motor neurons

    Directory of Open Access Journals (Sweden)

    Chwalla Barbara

    2008-07-01

    Full Text Available Abstract Background Developing neurons form dendritic trees with cell type-specific patterns of growth, branching and targeting. Dendrites of Drosophila peripheral sensory neurons have emerged as a premier genetic model, though the molecular mechanisms that underlie and regulate their morphogenesis remain incompletely understood. Still less is known about this process in central neurons and the extent to which central and peripheral dendrites share common organisational principles and molecular features. To address these issues, we have carried out two comparable gain-of-function screens for genes that influence dendrite morphologies in peripheral dendritic arborisation (da neurons and central RP2 motor neurons. Results We found 35 unique loci that influenced da neuron dendrites, including five previously shown as required for da dendrite patterning. Several phenotypes were class-specific and many resembled those of known mutants, suggesting that genes identified in this study may converge with and extend known molecular pathways for dendrite development in da neurons. The second screen used a novel technique for cell-autonomous gene misexpression in RP2 motor neurons. We found 51 unique loci affecting RP2 dendrite morphology, 84% expressed in the central nervous system. The phenotypic classes from both screens demonstrate that gene misexpression can affect specific aspects of dendritic development, such as growth, branching and targeting. We demonstrate that these processes are genetically separable. Targeting phenotypes were specific to the RP2 screen, and we propose that dendrites in the central nervous system are targeted to territories defined by Cartesian co-ordinates along the antero-posterior and the medio-lateral axes of the central neuropile. Comparisons between the screens suggest that the dendrites of peripheral da and central RP2 neurons are shaped by regulatory programs that only partially overlap. We focused on one common

  16. Turtle functions downstream of Cut in differentially regulating class specific dendrite morphogenesis in Drosophila.

    Directory of Open Access Journals (Sweden)

    Mikolaj J Sulkowski

    Full Text Available BACKGROUND: Dendritic morphology largely determines patterns of synaptic connectivity and electrochemical properties of a neuron. Neurons display a myriad diversity of dendritic geometries which serve as a basis for functional classification. Several types of molecules have recently been identified which regulate dendrite morphology by acting at the levels of transcriptional regulation, direct interactions with the cytoskeleton and organelles, and cell surface interactions. Although there has been substantial progress in understanding the molecular mechanisms of dendrite morphogenesis, the specification of class-specific dendritic arbors remains largely unexplained. Furthermore, the presence of numerous regulators suggests that they must work in concert. However, presently, few genetic pathways regulating dendrite development have been defined. METHODOLOGY/PRINCIPAL FINDINGS: The Drosophila gene turtle belongs to an evolutionarily conserved class of immunoglobulin superfamily members found in the nervous systems of diverse organisms. We demonstrate that Turtle is differentially expressed in Drosophila da neurons. Moreover, MARCM analyses reveal Turtle acts cell autonomously to exert class specific effects on dendritic growth and/or branching in da neuron subclasses. Using transgenic overexpression of different Turtle isoforms, we find context-dependent, isoform-specific effects on mediating dendritic branching in class II, III and IV da neurons. Finally, we demonstrate via chromatin immunoprecipitation, qPCR, and immunohistochemistry analyses that Turtle expression is positively regulated by the Cut homeodomain transcription factor and via genetic interaction studies that Turtle is downstream effector of Cut-mediated regulation of da neuron dendrite morphology. CONCLUSIONS/SIGNIFICANCE: Our findings reveal that Turtle proteins differentially regulate the acquisition of class-specific dendrite morphologies. In addition, we have established a

  17. Disruptive behavior in school. Wired up - the relationship between disruptive behavior and new technology.

    OpenAIRE

    Solberg, Stine

    2014-01-01

    Background: The thesis is part of the research project Disruptive behavior in school, led by professor Liv Duesund at the Department of Special Needs Education, University of Oslo. Professor Duesund is the supervisor of the thesis. It is a cooperation project between University of Oslo and University of California, Berkeley and compares the educational cultures of Norway an the United States (Duesund, 2013). The focus is on disruptive behavior, and in what ways behavior can vary in the two ...

  18. Functional changes of dendritic cells in hypersensivity reactions to amoxicillin

    Directory of Open Access Journals (Sweden)

    C.M.F. Lima

    2010-10-01

    Full Text Available A better understanding of dendritic cell (DC involvement in responses to haptenic drugs is needed, because it represents a possible approach to the development of an in vitro test, which could identify patients prone to drug allergies. There are two main DC subsets: plasmacytoid DC (pDC and myeloid DC (mDC. β-lactams form hapten-carrier conjugates and may provide a suitable model to study DC behavior in drug allergy reactions. It has been demonstrated that drugs interact differently with DC in drug allergic and non-allergic patients, but there are no studies regarding these subsets. Our aim was to assess the functional changes of mDC and pDC harvested from an amoxicillin-hypersensitive 32-year-old woman who experienced a severe maculopapular exanthema as reflected in interleukin-6 (IL-6 production after stimulation with this drug and penicillin. We also aim to demonstrate, for the first time, the feasibility of this method for dendritic cell isolation followed by in vitro stimulation for studies of drug allergy physiopathology. DC were harvested using a double Percoll density gradient, which generates a basophil-depleted cell (BDC suspension. Further, pDC were isolated by blood DC antigen 4-positive magnetic selection and gravity filtration through magnetized columns. After stimulation with amoxicillin, penicillin and positive and negative controls, IL-6 production was measured by ELISA. A positive dose-response curve for IL-6 after stimulation with amoxicillin and penicillin was observed for pDC, but not for mDC or BDC suspension. These preliminary results demonstrate the feasibility of this methodology to expand the knowledge of the effect of dendritic cell activation by drug allergens.

  19. Dendrite Growth Kinetics in Undercooled Melts of Intermetallic Compounds

    Directory of Open Access Journals (Sweden)

    Dieter M. Herlach

    2015-09-01

    Full Text Available Solidification needs an undercooling to drive the solidification front. If large undercoolings are achieved, metastable solid materials are solidified from the undercooled melt. Containerless processing provides the conditions to achieve large undercoolings since heterogeneous nucleation on container walls is completely avoided. In the present contribution both electromagnetic and electrostatic levitation are applied. The velocity of rapidly advancing dendrites is measured as a function of undercooling by a High-Speed-Camera. The dendrite growth dynamics is investigated in undercooled melts of intermetallic compounds. The Al50Ni50 alloy is studied with respect to disorder trapping that leads to a disordered superlattice structure if the melt is undercooled beyond a critical undercooling. Disorder trapping is evidenced by in situ energy dispersive diffraction using synchrotron radiation of high intensity to record full diffraction pattern on levitated samples within a short time interval. Experiments on Ni2B using different processing techniques of varying the level of convection reveal convection-induced faceting of rapidly growing dendrites. Eventually, the growth velocity is measured in an undercooled melt of glass forming Cu50Zr50 alloy. A maximum in the growth velocity–undercooling relation is proved. This is understood by the fact that the temperature dependent diffusion coefficient counteracts the thermodynamic driving force for rapid growth if the temperature of the undercooled melt is approaching the temperature regime above the glass transition temperature. The analysis of this result allows for determining the activation energy of atomic attachment kinetics at the solid–liquid interface that is comparable to the activation energy of atomic diffusion as determined by independent measurements of the atomic diffusion in undercooled Cu50Zr50 alloy melt.

  20. Dendritic Na(+) spikes enable cortical input to drive action potential output from hippocampal CA2 pyramidal neurons.

    Science.gov (United States)

    Sun, Qian; Srinivas, Kalyan V; Sotayo, Alaba; Siegelbaum, Steven A

    2014-01-01

    Synaptic inputs from different brain areas are often targeted to distinct regions of neuronal dendritic arbors. Inputs to proximal dendrites usually produce large somatic EPSPs that efficiently trigger action potential (AP) output, whereas inputs to distal dendrites are greatly attenuated and may largely modulate AP output. In contrast to most other cortical and hippocampal neurons, hippocampal CA2 pyramidal neurons show unusually strong excitation by their distal dendritic inputs from entorhinal cortex (EC). In this study, we demonstrate that the ability of these EC inputs to drive CA2 AP output requires the firing of local dendritic Na(+) spikes. Furthermore, we find that CA2 dendritic geometry contributes to the efficient coupling of dendritic Na(+) spikes to AP output. These results provide a striking example of how dendritic spikes enable direct cortical inputs to overcome unfavorable distal synaptic locale to trigger axonal AP output and thereby enable efficient cortico-hippocampal information flow.

  1. Utilizing dendritic scaffold for feasible formation of naphthalene excimer

    Indian Academy of Sciences (India)

    P K Lekha; Tufan Ghosh; Edamana Prasad

    2011-11-01

    Peripheral functionalization of PAMAM dendrimers with naphthalene units leads to significant ground state aggregation in the system above the critical aggregation concentrations (CAC). Upon photoexcitation of the ground state aggregates, static type excimer formation of naphthalene moiety is observed. Significant red-shifted emission from naphthalene excimers is achieved through generating the static type excimers in polar solvents such as methanol and acetonitrile-water mixtures. Control experiments suggest that the presence of dendritic scaffold in the system play a pivotal role in generating intense static excimer emission in naphthalene modified PAMAM dendrimers, in solution phase at room temperature.

  2. Dendritic cell-based cancer immunotherapy for colorectal cancer.

    Science.gov (United States)

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Saito, Keisuke; Takami, Shinichiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo

    2016-05-01

    Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the prognosis is extremely poor. The optimal sequence of therapy remains unknown. Therefore, alternative strategies, such as immunotherapy, are needed for patients with advanced CRC. This review summarizes evidence from dendritic cell-based cancer immunotherapy strategies that are currently in clinical trials. In addition, we discuss the possibility of antitumor immune responses through immunoinhibitory PD-1/PD-L1 pathway blockade in CRC patients. PMID:27158196

  3. A novel cell subset:Interferon-producing killer dendritic cells

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Recent reports introduce a novel cell subset of DCs with antigenic phenotypes shared by both NK cells and B cells, but without surface markers of pDCs and T cells, appearing to be a chimera of NK cells and DCs, namely interferon-producing killer dendritic cells(IKDCs).IKDCs not only secret type I and type II interferons to recognize and kill tumor cells effectively, but also express MHC-II molecules to present antigens.Thus, IKDCs are considered as important immunosurveilance cells for tumors, providing a link between innate and adaptive immunity.

  4. Spatiotemporal Dynamics of Dendritic Spines in the Living Brain

    Directory of Open Access Journals (Sweden)

    Chia-Chien eChen

    2014-05-01

    Full Text Available Dendritic spines are ubiquitous postsynaptic sites of most excitatory synapses in the mammalian brain, and thus may serve as structural indicators of functional synapses. Recent works have suggested that neuronal coding of memories may be associated with rapid alterations in spine formation and elimination. Technological advances have enabled researchers to study spine dynamics in vivo during development as well as under various physiological and pathological conditions. We believe that better understanding of the spatiotemporal patterns of spine dynamics will help elucidate the principles of experience-dependent circuit modification and information processing in the living brain.

  5. A summary about dendritic cells in skin diseases

    Institute of Scientific and Technical Information of China (English)

    Jianguo Huang; Robert Gniadecki

    2005-01-01

    Dendritic cellls (DCs) comprise an essential component of the immune system, are crucial in the initiation of antigen specific immune responses. In this summary we focus on summarizing on the central role of DCs in skin diseases: Bullous dermatoses,Dermatitis, Psoriasis, Lichen Planus , Graft-versus-host disease, Connect Tissue Diseases, Virus Diseases, Fungi Diseases, HIV, Urticaria, Urticaria pigmentosa, Mastocytosis, Tumour, Solar dermatoses. Moreover, in this summary we review the distribution and phenotype of DCs in human skin. Markers and phenotyps ' s study have provided strong support for a concept in which DCs play an important role in the pothogenesis of some skin diseases.

  6. Classification of dendritic cell phenotypes from gene expression data

    Directory of Open Access Journals (Sweden)

    Zolezzi Francesca

    2011-08-01

    Full Text Available Abstract Background The selection of relevant genes for sample classification is a common task in many gene expression studies. Although a number of tools have been developed to identify optimal gene expression signatures, they often generate gene lists that are too long to be exploited clinically. Consequently, researchers in the field try to identify the smallest set of genes that provide good sample classification. We investigated the genome-wide expression of the inflammatory phenotype in dendritic cells. Dendritic cells are a complex group of cells that play a critical role in vertebrate immunity. Therefore, the prediction of the inflammatory phenotype in these cells may help with the selection of immune-modulating compounds. Results A data mining protocol was applied to microarray data for murine cell lines treated with various inflammatory stimuli. The learning and validation data sets consisted of 155 and 49 samples, respectively. The data mining protocol reduced the number of probe sets from 5,802 to 10, then from 10 to 6 and finally from 6 to 3. The performances of a set of supervised classification models were compared. The best accuracy, when using the six following genes --Il12b, Cd40, Socs3, Irgm1, Plin2 and Lgals3bp-- was obtained by Tree Augmented Naïve Bayes and Nearest Neighbour (91.8%. Using the smallest set of three genes --Il12b, Cd40 and Socs3-- the performance remained satisfactory and the best accuracy was with Support Vector Machine (95.9%. These data mining models, using data for the genes Il12b, Cd40 and Socs3, were validated with a human data set consisting of 27 samples. Support Vector Machines (71.4% and Nearest Neighbour (92.6% gave the worst performances, but the remaining models correctly classified all the 27 samples. Conclusions The genes selected by the data mining protocol proposed were shown to be informative for discriminating between inflammatory and steady-state phenotypes in dendritic cells. The

  7. Numerical Simulation of Dendrite Evolution during Solidification Process

    Institute of Scientific and Technical Information of China (English)

    LI Qiang; GUO Qiao-yi; REN Chuan-fu

    2005-01-01

    In order to precisely describe the dendrite evolution during solidification process, especially in microscale, a continuous method is presented to deal with the discontinuous physical properties beside the solid/liquid interface. In this method, the physical properties are used as averaging physical properties of solid phase and liquid phase in the interface zone, which can smooth the property gap between solid and liquid phases, and make the properties from liquid phase to solid phase. The simulated results show that the method can represent the sidebranches and the solute micro-segregation well.

  8. A novel cell subset: Interferon-producing killer dendritic cells

    Institute of Scientific and Technical Information of China (English)

    WANG JiongKun; XING FeiYue

    2008-01-01

    Recent reports introduce a novel cell subset of DCs with antigenic phenotypes shared by both NK cells and B cells, but without surface markers of pDCs and T cells, appearing to be a chimera of NK cells and DCs, namely interferon-producing killer dendritic cells (IKDCs). IKDCs not only secret type Ⅰ and type Ⅱ interferons to recognize and kill tumor cells effectively, but also express MHC-Ⅱ molecules to present antigens. Thus, IKDCs are considered as important immunosurveilance cells for tumors, providing a link between innate and adaptive immunity.

  9. Suppressing The Growth Of Dendrites In Secondary Li Cells

    Science.gov (United States)

    Davies, Evan D.; Perrone, David E.; Shen, David H.

    1996-01-01

    Proposed technique for suppressing growth of lithium dendrites in rechargeable lithium electrochemical power cells involves periodic interruption of steady charging current with short, high-current discharge pulses. Technique applicable to lithium cells of several different types, including Li/TiS(2), Li/NbSe(3), Li/CoO(2), Li/MoS(2), Li/Vo(x), and Li/MnO(2). Cells candidates for use in spacecraft, military, communications, automotive, and other applications in which high-energy-density rechargeable batteries needed.

  10. Targeting dendritic cells in vivo for cancer therapy

    Directory of Open Access Journals (Sweden)

    Irina eCaminschi

    2012-02-01

    Full Text Available Monoclonal antibodies that recognise cell surface molecules have been used deliver antigenic cargo to dendritic cells (DC for induction of immune responses. The encouraging anti-tumour immunity elicited using this immunisation strategy suggests its suitability for clinical trials. This review discusses the complex network of DC, the functional specialisation of DC-subsets, the immunological outcomes of targeting different DC-subsets and their cell surface receptors, and the requirements for the induction of effective anti-tumour immunity. Finally, we review preclinical experiments and the progress towards targeting human DC in vivo.

  11. Role of plasmacytoid dendritic cell subsets in allergic asthma

    OpenAIRE

    Maazi, Hadi; Lam, Jonathan; Lombardi, Vincent; Akbari, Omid

    2013-01-01

    Plasmacytoid dendritic cells (pDCs) are major type-I interferon producing cells that play important roles in antiviral immunity and tolerance induction. These cells share a common DC progenitor with conventional DCs and Fms-like tyrosine kinase-3 ligand is essential for their development. Several subsets of pDCs have been identified to date including CCR9+, CD9+ and CD2+ pDCs. Recently, three subsets of pDCs were described namely, CD8α−β−, CD8α+β− and CD8α+β+ subsets. Interestingly, CD8α+β− a...

  12. Dendritic cell-based cancer immunotherapy for colorectal cancer.

    Science.gov (United States)

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Saito, Keisuke; Takami, Shinichiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo

    2016-05-01

    Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the prognosis is extremely poor. The optimal sequence of therapy remains unknown. Therefore, alternative strategies, such as immunotherapy, are needed for patients with advanced CRC. This review summarizes evidence from dendritic cell-based cancer immunotherapy strategies that are currently in clinical trials. In addition, we discuss the possibility of antitumor immune responses through immunoinhibitory PD-1/PD-L1 pathway blockade in CRC patients.

  13. The known unknowns of the human dendritic cell network

    Directory of Open Access Journals (Sweden)

    Mélanie eDurand

    2015-03-01

    Full Text Available Dendritic cells (DC initiate and orient immune responses and comprise several subsets that display distinct phenotypes and properties. Most of our knowledge of DC subsets biology is based on mouse studies. In the past few years, the alignment of the human DC network with the mouse DC network has been the focus of much attention. Although comparative phenotypic and transcriptomic analysis have shown a high level of homology between mouse and human DC subsets, significant differences in phenotype and function have also been evidenced. Here we review recent advances in our understanding of the human DC network and discuss some remaining gaps and future challenges of the human DC field.

  14. Longitudinal association between marital disruption and child BMI and obesity.

    Science.gov (United States)

    Arkes, Jeremy

    2012-08-01

    This research examines whether family disruptions (i.e., divorces and separation) contribute to children's weight problems. The sample consists of 7,299 observations for 2,333 children, aged 5-14, over the 1986-2006 period, from a US representative sample from the Child and Young Adult Survey accompanying the National Longitudinal Survey of Youth (NLSY). The study uses individual-fixed-effects models in a longitudinal framework to compare children's BMI and weight problems before and after a disruption. Furthermore, besides doing a before-after comparison for children, the study also estimates the effects at various periods relative to the disruption in order to examine whether children are affected before the disruption and whether any effects change as time passes from the disruption, as some effects may be temporary or slow to develop. Despite having a larger sample than the previous studies, the results provide no evidence that, on average, children's BMI and BMI percentile scores (measured with continuous outcomes) are affected before the disruption, after the disruption, and as time passes from the disruption, relative to a baseline period a few years before the disruption. However, children experiencing a family disruption do have an increased risk of obesity (having a BMI percentile score of 95 or higher) in the two years leading up to the disruption as well as after the disruption, and as time passes from the disruption. PMID:22484366

  15. Targeted pruning of a neuron’s dendritic tree via femtosecond laser dendrotomy

    Science.gov (United States)

    Go, Mary Ann; Choy, Julian Min Chiang; Colibaba, Alexandru Serban; Redman, Stephen; Bachor, Hans-A.; Stricker, Christian; Daria, Vincent Ricardo

    2016-01-01

    Neurons are classified according to action potential firing in response to current injection. While such firing patterns are shaped by the composition and distribution of ion channels, modelling studies suggest that the geometry of dendritic branches also influences temporal firing patterns. Verifying this link is crucial to understanding how neurons transform their inputs to output but has so far been technically challenging. Here, we investigate branching-dependent firing by pruning the dendritic tree of pyramidal neurons. We use a focused ultrafast laser to achieve highly localized and minimally invasive cutting of dendrites, thus keeping the rest of the dendritic tree intact and the neuron functional. We verify successful dendrotomy via two-photon uncaging of neurotransmitters before and after dendrotomy at sites around the cut region and via biocytin staining. Our results show that significantly altering the dendritic arborisation, such as by severing the apical trunk, enhances excitability in layer V cortical pyramidal neurons as predicted by simulations. This method may be applied to the analysis of specific relationships between dendritic structure and neuronal function. The capacity to dynamically manipulate dendritic topology or isolate inputs from various dendritic domains can provide a fresh perspective on the roles they play in shaping neuronal output.

  16. GABA-A receptor inhibition of local calcium signaling in spines and dendrites.

    Science.gov (United States)

    Marlin, Joseph J; Carter, Adam G

    2014-11-26

    Cortical interneurons activate GABA-A receptors to rapidly control electrical and biochemical signaling at pyramidal neurons. Different populations of interneurons are known to uniquely target the soma and dendrites of pyramidal neurons. However, the ability of these interneurons to inhibit Ca(2+) signaling at spines and dendrites is largely unexplored. Here we use whole-cell recordings, two-photon microscopy, GABA uncaging and optogenetics to study dendritic inhibition at layer 5 (L5) pyramidal neurons in slices of mouse PFC. We first show that GABA-A receptors strongly inhibit action potential (AP)-evoked Ca(2+) signals at both spines and dendrites. We find robust inhibition over tens of milliseconds that spreads along the dendritic branch. However, we observe no difference in the amount of inhibition at neighboring spines and dendrites. We then examine the influence of interneurons expressing parvalbumin (PV), somatostatin (SOM), or 5HT3a receptors. We determine that these populations of interneurons make unique contacts onto the apical and basal dendrites of L5 pyramidal neurons. We also show that SOM and 5HT3a but not PV interneurons potently inhibit AP Ca(2+) signals via GABA-A receptors at both spines and dendrites. These findings reveal how multiple interneurons regulate local Ca(2+) signaling in pyramidal neurons, with implications for cortical function and disease.

  17. From Synaptic Transmission to Cognition: An Intermediary Role for Dendritic Spines

    Science.gov (United States)

    Gonzalez-Burgos, Ignacio

    2012-01-01

    Dendritic spines are cytoplasmic protrusions that develop directly or indirectly from the filopodia of neurons. Dendritic spines mediate excitatory neurotransmission and they can isolate the electrical activity generated by synaptic impulses, enabling them to translate excitatory afferent information via several types of plastic changes, including…

  18. Electrochemical migration of tin in electronics and microstructure of the dendrites

    DEFF Research Database (Denmark)

    Minzari, Daniel; Grumsen, Flemming Bjerg; Jellesen, Morten Stendahl;

    2011-01-01

    microscopy including Energy dispersive X-ray spectroscopy and electron diffraction. The tin dendrites were formed under 5 or 12V potential bias in 10ppm by weight NaCl electrolyte as a micro-droplet on the resistor during electrochemical migration experiments. The dendrites formed were found to have...

  19. NMDAR-regulated dynamics of layer 4 neuronal dendrites during thalamocortical reorganization in neonates.

    Science.gov (United States)

    Mizuno, Hidenobu; Luo, Wenshu; Tarusawa, Etsuko; Saito, Yoshikazu M; Sato, Takuya; Yoshimura, Yumiko; Itohara, Shigeyoshi; Iwasato, Takuji

    2014-04-16

    Thalamocortical (TC) connectivity is reorganized by thalamic inputs during postnatal development; however, the dynamic characteristics of TC reorganization and the underlying mechanisms remain unexplored. We addressed this question using dendritic refinement of layer 4 (L4) stellate neurons in mouse barrel cortex (barrel cells) as a model; dendritic refinement of L4 neurons is a critical component of TC reorganization through which postsynaptic L4 neurons acquire their dendritic orientation toward presynaptic TC axon termini. Simultaneous labeling of TC axons and individual barrel cell dendrites allowed in vivo time-lapse imaging of dendritic refinement in the neonatal cortex. The barrel cells reinforced the dendritic orientation toward TC axons by dynamically moving their branches. In N-methyl-D-aspartate receptor (NMDAR)-deficient barrel cells, this dendritic motility was enhanced, and the orientation bias was not reinforced. Our data suggest that L4 neurons have "fluctuating" dendrites during TC reorganization and that NMDARs cell autonomously regulate these dynamics to establish fine-tuned circuits.

  20. A Numerical Study for the Relationship between Natural Manganese Dendrites and DLA Patterns

    Science.gov (United States)

    Ozbey, Tugba; Bayirli, Mehmet

    2016-03-01

    The formation mechanisms and the origin of manganese dendrites on the magnesite ore have been under discussion. The growth process of the manganese dendrites is statistically studied by comparing them to aggregations obtained according to the diffusion limited aggregation (DLA) model via Monte Carlo simulations. In this case, ten manganese dendrite patterns changing from the least dense to the densest aggregations on the surface are separately selected to determine the relationship between real and simulated patterns. The sticking parameter is ranged from 0.05≤t≤1. The density-density correlation functions C(r) (their critical exponent A), fractal dimension Df, critical exponent α, and critical exponent β pertaining to the root mean square (rms) thickness have been computed for both the ten manganese dendrites and the simulated aggregations representing them. The results indicate that manganese dendrites may be determined with the general DLA model. Analyses of manganese dendrites, both scaling and simulations, suggest the growth mechanism for the macroscopic expression of crystalline anisotropy for the dendritic patterns. These results are in good agreement with the values in other literature and can be helpful in comparing natural and simulated aggregations (both dendritic and compact deposits).

  1. Development of Type 1 Diabetes: Monocytes and dendritic cells in the pancreas

    NARCIS (Netherlands)

    J.M.C. Welzen-Coppens (Jojanneke)

    2013-01-01

    textabstractThis thesis focuses on the presence of precursors for dendritic cells and the characterization of dendritic cell subsets in the normal pancreas in mice and humans as well as in the pancreas of the NOD mouse, a type 1 diabetes mouse model. Therefore, we give a short introduction to dendri

  2. Activity-dependent control of neuronal output by local and global dendritic spike attenuation.

    Science.gov (United States)

    Remy, Stefan; Csicsvari, Jozsef; Beck, Heinz

    2009-03-26

    Neurons possess elaborate dendritic arbors which receive and integrate excitatory synaptic signals. Individual dendritic subbranches exhibit local membrane potential supralinearities, termed dendritic spikes, which control transfer of local synaptic input to the soma. Here, we show that dendritic spikes in CA1 pyramidal cells are strongly regulated by specific types of prior input. While input in the linear range is without effect, supralinear input inhibits subsequent spikes, causing them to attenuate and ultimately fail due to dendritic Na(+) channel inactivation. This mechanism acts locally within the boundaries of the input branch. If an input is sufficiently strong to trigger axonal action potentials, their back-propagation into the dendritic tree causes a widespread global reduction in dendritic excitability which is prominent after firing patterns occurring in vivo. Together, these mechanisms control the capability of individual dendritic branches to trigger somatic action potential output. They are invoked at frequencies encountered during learning, and impose limits on the storage and retrieval rates of information encoded as branch excitability. PMID:19323999

  3. Alloy substantially free of dendrites and method of forming the same

    Science.gov (United States)

    de Figueredo, Anacleto M.; Apelian, Diran; Findon, Matt M.; Saddock, Nicholas

    2009-04-07

    Described herein are alloys substantially free of dendrites. A method includes forming an alloy substantially free of dendrites. A superheated alloy is cooled to form a nucleated alloy. The temperature of the nucleated alloy is controlled to prevent the nuclei from melting. The nucleated alloy is mixed to distribute the nuclei throughout the alloy. The nucleated alloy is cooled with nuclei distributed throughout.

  4. Upregulated H-Current in hyperexcitable CA1 dendrites after febrile seizures

    Directory of Open Access Journals (Sweden)

    Jonas Dyhrfjeld-Johnsen

    2008-04-01

    Full Text Available Somatic recordings from CA1 pyramidal cells indicated a persistent upregulation of the h-current (Ih after experimental febrile seizures. Here, we examined febrile seizure-induced long-term changes in Ih and neuronal excitability in CA1 dendrites. Cell-attached recordings showed that dendritic Ih was significantly upregulated, with a depolarized half-activation potential and increased maximal current. Although enhanced Ih is typically thought to be associated with decreased dendritic excitability, whole-cell dendritic recordings revealed a robust increase in action potential firing after febrile seizures. We turned to computational simulations to understand how the experimentally observed changes in Ih influence dendritic excitability. Unexpectedly, the simulations, performed in three previously published CA1 pyramidal cell models, showed that the experimentally observed increases in Ih resulted in a general enhancement of dendritic excitability, primarily due to the increased Ih-induced depolarization of the resting membrane potential overcoming the excitability-depressing effects of decreased dendritic input resistance. Taken together, these experimental and modeling results reveal that, contrary to the exclusively anti-convulsive role often attributed to increased Ih in epilepsy, the enhanced Ih can co-exist with, and possibly even contribute to, persistent dendritic hyperexcitability following febrile seizures in the developing hippocampus.

  5. Calcium spikes and calcium plateaux evoked by differential polarization in dendrites of turtle motoneurones in vitro

    DEFF Research Database (Denmark)

    Hounsgaard, J; Kiehn, O

    1993-01-01

    The ability of dendrites in turtle motoneurones to support calcium spikes and calcium plateaux was investigated using differential polarization by applied electric fields. 2. Electric fields were generated by passing current through transverse slices of the turtle spinal cord between two plate......+ spikes and Ca2+ plateaux are present in dendrites of spinal motoneurones of the turtle....

  6. Synthesis of Dendritic-Linear Block Copolymers by Atom Transfer Radical Polymerization

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The dendritic polyarylether 2-bromoisobutyrate as the macromolecular initiator for the controlled free radical polymerization of styrene was investigated. The polymerization was carried out with CuBr/2,2′-bipyridine catalyst at 110℃. It is found that the hybrid dendritic-linear block copolymers possess well-defined molecular weights and low polydispersities.

  7. Identification of a novel immunoregulatory signaling pathway exploited by M. tuberculosis in dendritic cells

    DEFF Research Database (Denmark)

    Laursen, Janne Marie; Schoof, Erwin; Søndergaard, Jonas Nørskov;

    highly sophisticated infectious machinery employed by the bacterium. The dendritic cell (DC) plays a crucial role in shaping the nature of the immune response after exposure to pathogens, and the interaction between M. tuberculosis and the dendritic cell is of profound importance for the course of...

  8. Disruption of cytoplasmic microtubules by ultraviolet radiation

    International Nuclear Information System (INIS)

    Ultraviolet (UV) irradiation of cultured human skin fibroblasts causes the disassembly of their microtubules. Using indirect immunofluorescence microscopy, we have now investigated whether damage to the microtubule precursor pool may contribute to the disruption of microtubules. Exposure to polychromatic UV radiation inhibits the reassembly of microtubules during cellular recovery from cold treatment. In addition, the ability of taxol to promote microtubule polymerization and bundling is inhibited in UV-irradiated cells. However, UV irradiation of taxol-pretreated cells or in situ detergent-extracted microtubules fails to disrupt the microtubule network. These data suggest that damage to dimeric tubulin, or another soluble factor(s) required for polymerization, contributes to the disassembly of microtubules in UV-irradiated human skin fibroblasts

  9. The hexagon hypothesis: Six disruptive scenarios.

    Science.gov (United States)

    Burtles, Jim

    2015-01-01

    This paper aims to bring a simple but effective and comprehensive approach to the development, delivery and monitoring of business continuity solutions. To ensure that the arguments and principles apply across the board, the paper sticks to basic underlying concepts rather than sophisticated interpretations. First, the paper explores what exactly people are defending themselves against. Secondly, the paper looks at how defences should be set up. Disruptive events tend to unfold in phases, each of which invites a particular style of protection, ranging from risk management through to business continuity to insurance cover. Their impact upon any business operation will fall into one of six basic scenarios. The hexagon hypothesis suggests that everyone should be prepared to deal with each of these six disruptive scenarios and it provides them with a useful benchmark for business continuity. PMID:26420396

  10. Endocrine disrupters. The case of estrogen xenobiotics

    Directory of Open Access Journals (Sweden)

    N. Olea Serrano

    2001-06-01

    Full Text Available Interest of the scientific community in chemical substances able to alter the hormone balance –endocrine disrupters- has grown with increasing evidence of the consequences for animal populations of exposure to these substances. As has occurred on previous occasions, observational data on animal populations have been sufficiently suggestive to cause concerns among clinicians that similar effects may be produced in human populations. Although data on the effects on populations of animals are more easily generated than those on individuals, clinical observations on human individuals alongside the few existing epidemiological studies have shown a certain parallelism. Indeed, in vitro and in vivo models have been able to designate many chemical compounds as hormonal mimics, including both natural and human-produced compounds to which there are exposure risks. The present work reviews the conceptual premises of endocrine disruption and the development of the use of this term.

  11. Cloning and disruption of Ustilago maydis genes.

    OpenAIRE

    Fotheringham, S.; Holloman, W K

    1989-01-01

    We have demonstrated that genes from Ustilago maydis can be cloned by direct complementation of mutants through the use of genomic libraries made in a high-frequency transformation vector. We isolated a gene involved in amino acid biosynthesis as an illustrative example and showed that integrative and one-step disruption methods can be used to create null mutations in the chromosomal copy of the gene by homologous recombination. The results of this investigation make it clear that one-step ge...

  12. The Impact of Disruptive Innovations in Orthopaedics

    OpenAIRE

    Hansen, Erik; Bozic, Kevin J.

    2009-01-01

    The US healthcare system is currently facing daunting demographic and economic challenges. Because musculoskeletal disorders and disease represent a substantial and growing portion of this healthcare burden, novel approaches will be needed to continue to provide high-quality, affordable, and accessible orthopaedic care to our population. The concept of “disruptive innovations,” which has been studied and popularized by Harvard Business School Professor Clayton Christensen, may offer a potenti...

  13. Disruption strategies for online child pornography networks

    OpenAIRE

    Joffres, Kilauea

    2012-01-01

    The advent of the Internet has allowed for the creation of online child pornography networks, in which websites link to one another and facilitate access to child pornographic materials. This project seeks to use social network analysis tools to identify effective disruption strategies against online child pornography networks. For this purpose, four networks of child exploitation material were extracted using a specially designed web-crawler. These networks were then submitted to three diffe...

  14. Mechanical properties and disruption of dental biofilms

    OpenAIRE

    Rmaile, Amir

    2013-01-01

    A literature review of dental plaque biofilms formation, progression and detachment mechanisms is presented in this thesis. Various strategies that have been employed to reduce or eliminate dental biofilms are discussed. The focus of the thesis was on the mechanical properties and disruption of dental biofilms, especially from hard-to-access areas of the oral cavity, such as the interproximal (IP) sites between the teeth. Various methods to measure mechanical properties of dental biofilms wer...

  15. Language adapts to signal disruption in interaction

    OpenAIRE

    Macuch Silva, V.; Roberts, S

    2016-01-01

    Linguistic traits are often seen as reflecting cognitive biases and constraints (e.g. Christiansen & Chater, 2008). However, language must also adapt to properties of the channel through which communication between individuals occurs. Perhaps the most basic aspect of any communication channel is noise. Communicative signals can be blocked, degraded or distorted by other sources in the environment. This poses a fundamental problem for communication. On average, channel disruption accompanies p...

  16. Will disruptive innovations cure health care?

    Science.gov (United States)

    Christensen, C M; Bohmer, R; Kenagy, J

    2000-01-01

    It's no secret that health care delivery is convoluted, expensive, and often deeply dissatisfying to consumers. But what is less obvious is that a way out of this crisis exists. Simpler alternatives to expensive care are already here--everything from $5 eyeglasses that people can use to correct their own vision to angioplasty instead of open-heart surgery. Just as the PC replaced the mainframe and the telephone replaced the telegraph operator, disruptive innovations are changing the landscape of health care. Nurse practitioners, general practitioners, and even patients can do things in less-expensive, decentralized settings that could once be performed only by expensive specialists in centralized, inconvenient locations. But established institutions--teaching hospitals, medical schools, insurance companies, and managed care facilities--are fighting these innovations tooth and nail. Instead of embracing change, they're turning the thumbscrews on their old processes--laying off workers, delaying payments, merging, and adding layers of overhead workers. Not only is this at the root of consumer dissatisfaction with the present system, it sows the seeds of its own destruction. The history of disruptive innovations tells us that incumbent institutions will be replaced with ones whose business models are appropriate to the new technologies and markets. Instead of working to preserve the existing systems, regulators, physicians, and pharmaceutical companies need to ask how they can enable more disruptive innovations to emerge. If the natural process of disruption is allowed to proceed, the result will be higher quality, lower cost, more convenient health care for everyone. PMID:11143147

  17. Disruption of vitamin A metabolism by dioxin

    OpenAIRE

    Högberg, Pi

    2003-01-01

    Vitamin A (retinoids) is a nutrient that plays a central role in development and remains essential for cell growth and differentiation throughout life. Dioxins are polychlorinated organic pollutants known to negatively affect the storage and body clearance of retinoids. This work aimed at studying mechanisms and consequences of dioxin-induced retinoid disruption in vivo. As model compound we used 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and as model species adult male S...

  18. Robust scheduling and disruption recovery for airlines

    OpenAIRE

    Eggenberg, Niklaus; Salani, Matteo

    2009-01-01

    Airline planning include complex and structured operations that must be planned in advance in order to exploit the available resources, provide a reliable and competitive service and forecast system's performances. Decisions regarding operations are based on data which is frequently due to uncertainty. Moreover, unpredicted events may disrupt the current schedule and force managers to take reactive decisions to recover to an operational state. On the other hand, proactive decisions, i.e. deci...

  19. Phase-field simulation of dendritic growth for binary alloys with complicate solution models

    Institute of Scientific and Technical Information of China (English)

    LI Xin-zhong; GUO Jing-jie; SU Yan-qing; WU Shi-ping; FU Heng-zhi

    2005-01-01

    A phase-field method for simulation of dendritic growth in binary alloys with complicate solution models was studied. The free energy densities of solid and liquid used to construct the free energy of a solidification system in the phase-field model were derived from the Calphad thermodynamic modeling of phase diagram. The dendritic growth of Ti-Al alloy with a quasi-sub regular solution model was simulated in both an isothermal and a nonisothermal regime. In the isothermal one, different initial solute compositions and melt temperatures were chosen.And in the non-isothermal one, release of latent heat during solidification was considered. Realistic growth patterns of dendrite are derived. Both the initial compositions and melt temperatures affect isothermal dendritic morphology and solute distributions much, especially the latter. Release of latent heat will cause a less developed structure of dendrite and a lower interfacial composition.

  20. Inhibitory control of linear and supralinear dendritic excitation in CA1 pyramidal neurons.

    Science.gov (United States)

    Müller, Christina; Beck, Heinz; Coulter, Douglas; Remy, Stefan

    2012-09-01

    The transformation of dendritic excitatory synaptic inputs to axonal action potential output is the fundamental computation performed by all principal neurons. We show that in the hippocampus this transformation is potently controlled by recurrent inhibitory microcircuits. However, excitatory input on highly excitable dendritic branches could resist inhibitory control by generating strong dendritic spikes and trigger precisely timed action potential output. Furthermore, we show that inhibition-sensitive branches can be transformed into inhibition-resistant, strongly spiking branches by intrinsic plasticity of branch excitability. In addition, we demonstrate that the inhibitory control of spatially defined dendritic excitation is strongly regulated by network activity patterns. Our findings suggest that dendritic spikes may serve to transform correlated branch input into reliable and temporally precise output even in the presence of inhibition.

  1. Radial macrosegregation and dendrite clustering in directionally solidified Al-7Si and Al-19Cu alloys

    Science.gov (United States)

    Ghods, M.; Johnson, L.; Lauer, M.; Grugel, R. N.; Tewari, S. N.; Poirier, D. R.

    2016-05-01

    Hypoeutectic Al-7 wt% Si and Al-19 wt% Cu alloys were directionally solidified upward in a Bridgman furnace through a range of constant growth speeds and thermal gradients. Though processing is thermo-solutally stable, flow initiated by gravity-independent advection at, slightly leading, central dendrites moves rejected solute out ahead and across the advancing interface. Here any lagging dendrites are further suppressed which promotes a curved solid-liquid interface and the eventual dendrite "clustering" seen in transverse sections (dendrite "steepling" in longitudinal orientations) as well as extensive radial macrosegregation. Both aluminum alloys showed considerable macrosegregation at the low growth speeds (10 and 30 μm s-1) but not at higher speed (72 μm s-1). Distribution of the fraction eutectic-constituent on transverse sections was determined in order to quantitatively describe radial macrosegregation. The convective mechanisms leading to dendrite-steepling were elucidated with numerical simulations, and their results compared with the experimental observations.

  2. Self-organized dendritic sidebranching in directional solidification: sidebranch coherence within uncorrelated bursts.

    Science.gov (United States)

    Pocheau, Alain; Bodea, Simona; Georgelin, Marc

    2009-09-01

    We experimentally study the level of organization of dendritic sidebranching in directional solidification. For this, we extract successive interface positions at a fixed distance from the dendrite tips and we perform various correlation analyses. The sidebranching signals appear composed of randomly distributed bursts in which sidebranching coherence is surprisingly large and robust. This is attested by the large autocorrelation found in single bursts and the large cross-correlation found in any couple of bursts, even belonging to different sides of a dendrite or to different dendrites. However, the phase coherence of sidebranching breaks down at the transition between bursts. This restricts the coherence of extended sidebranching signals to a mean burst length and prevents the occurrence of large scale cross-correlation between them. This balanced view on sidebranching coherence stresses the capability of self-organization of dendrites in material science and sheds light on the nature of sidebranching on curved growing forms.

  3. Synthesis of palladium dendritic nanostructures on amidoxime modified polyacrylonitrile fibers through a complexing-reducing method

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Zhichuan; Zhang, Yong; Wang, Bo; Qian, Guixiang; Tao, Tingxian, E-mail: tingxiantao@yahoo.cn

    2013-08-20

    Highlights: • We report the assembly of Pd dendritic nanostructures on amidoxime modified polyacrylonitrile fibers. • The supply rate of the metallic Pd plays a critical role in the morphology of Pd nanostructures. • The possible mechanism of Pd dendritic nanostructures on fibers was proposed. -- Abstract: In this paper, three-dimensional fern-leaf-like palladium (Pd) dendritic nanostructures were successfully synthesized on amidoxime modified polyacrylonitrile fibers via a simple and efficient complexing-reducing method. The influence of reaction time, temperature, and concentrations of N{sub 2}H{sub 4} and Fe{sup 3+} on the morphology and structure of Pd nanostructures was investigated. The results indicate that the supply rate of metallic Pd atoms plays a crucial role in the formation of the dendritic nanostructures. The formation mechanism of Pd dendritic nanostructures was proposed.

  4. Phase-field simulation of dendritic sidebranching induced by thermal noise

    Institute of Scientific and Technical Information of China (English)

    朱昌盛; 王智平; 荆涛; 柳百成

    2004-01-01

    The influence of undercooling and noise magnitude on dendritic sidebranching during crystal growth was investigated by simulation of a phase-field model which incorporates thermal noise. It is shown that, the sidebranching is not influenced with inclusion of the nonconserved noise, therefore, in order to save the computational costs it is often neglected; while conserved noise drives the morphological instability and is dominant origin of sidebranching. The dependence of temperature field on magnitude of thermal noise is apparent, when Fu gets an appropriate value, noise can induce sidebranching but not influence the dendritic tip operating state. In the small undercooled melt, the thermal diffusion layer collected around the dendrite is thick, which suppresses the growth of its sidebranching and makes the dendrite take on the morphology of no sidebranching, but when the undercooling is great,the thermal diffusion layer is thin, which is advantageous to the growth of the sidebranching and the dendrite presents the morphology of the developed sidebranching.

  5. Non-dendritic structural 7075 aluminum alloy byliquidus cast and its semi-solid compression behavior

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Fine, equiaxed, non-dendritic structure needed by semi-solid processing was obtained by liquidus cast, i.e.7075 wrought aluminum alloy cast from liquidus temperature. The microstructures after heat treatment at different tem-peratures and time in the semi-solid range were observed, and the compression deformation behavior at different tempera-tures (490 ~ 600 C) and strain rates (5 × 10-3 ~ 5s-1) was investigated by means of Gleeble-1500 thermal-mechenicalsimulator. Thc results show that the deformation resistance of the non-dendritic structure attained by liquidus cast in semi-solid is remarkably lower than that of conventional dendritic structure. The formability of non-dendritic structure is betterthan that of dendritic structure

  6. Measurements of Dendritic Growth Velocities in Undercooled Melts of Pure Nickel Under Static Magnetic Fields

    Science.gov (United States)

    Gao, Jianrong; Zhang, Zongning; Zhang, Yingjie

    2012-01-01

    Dendritic growth velocities in undercooled melts of pure Ni have been intensively studied over the past fifty years. However, the literature data are at marked variance with the prediction of the widely accepted model for rapid dendritic growth both at small and at large undercoolings. In the present work, bulk melts of pure Ni samples of high purity were undercooled by glass fluxing treatment under a static magnetic field. The recalescence processes of the samples at different undercoolings were recorded using a high-speed camera, and were modeled using a software to determine the dendritic growth velocities. The present data confirmed the effect of melt flow on dendritic growth velocities at undercoolings below 100 K. A comparison of the present data with previous measurements on a lower purity material suggested an effect of impurities on dendritic growth velocities at undercoolings larger than 200 K as well.

  7. Phase field modeling for dendritic morphology transition and micro-segregation in multi-component alloys

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    By using the phase field model for the solidification of multi-component alloys and coupling with real thermodynamic data, the dendritic morphology transition and the dendritic micro-segregation of Ni-Al-Nb ternary alloys are simulated in two cases, i.e., varying the alloy composition at a fixed under-cooling and varying the undercooling at a fixed alloy composition. The simulated results indicate that with the increase of the dimensionless undercooling U (U=ΔT/ΔT0, where ΔT is the undercooling and ΔT0 the temperature interval between the solidus and liquidus), the dendritic morphology transfers from dendritic to globular growth in both cases. As to the dendritic micro-segregation, both cases present a regularity of increasing at first and then decreasing.

  8. DMPD: Proximal effects of Toll-like receptor activation in dendritic cells. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17142025 Proximal effects of Toll-like receptor activation in dendritic cells. Watt...) (.svg) (.html) (.csml) Show Proximal effects of Toll-like receptor activation in dendritic cells. PubmedID... 17142025 Title Proximal effects of Toll-like receptor activation in dendritic ce

  9. DMPD: The role of type I interferon production by dendritic cells in host defense. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17544561 The role of type I interferon production by dendritic cells in host defens...tml) (.csml) Show The role of type I interferon production by dendritic cells in host defense. PubmedID 1754...4561 Title The role of type I interferon production by dendritic cells in host de

  10. Fine and distributed subcellular retinotopy of excitatory inputs to the dendritic tree of a collision-detecting neuron.

    Science.gov (United States)

    Zhu, Ying; Gabbiani, Fabrizio

    2016-06-01

    Individual neurons in several sensory systems receive synaptic inputs organized according to subcellular topographic maps, yet the fine structure of this topographic organization and its relation to dendritic morphology have not been studied in detail. Subcellular topography is expected to play a role in dendritic integration, particularly when dendrites are extended and active. The lobula giant movement detector (LGMD) neuron in the locust visual system is known to receive topographic excitatory inputs on part of its dendritic tree. The LGMD responds preferentially to objects approaching on a collision course and is thought to implement several interesting dendritic computations. To study the fine retinotopic mapping of visual inputs onto the excitatory dendrites of the LGMD, we designed a custom microscope allowing visual stimulation at the native sampling resolution of the locust compound eye while simultaneously performing two-photon calcium imaging on excitatory dendrites. We show that the LGMD receives a distributed, fine retinotopic projection from the eye facets and that adjacent facets activate overlapping portions of the same dendritic branches. We also demonstrate that adjacent retinal inputs most likely make independent synapses on the excitatory dendrites of the LGMD. Finally, we show that the fine topographic mapping can be studied using dynamic visual stimuli. Our results reveal the detailed structure of the dendritic input originating from individual facets on the eye and their relation to that of adjacent facets. The mapping of visual space onto the LGMD's dendrites is expected to have implications for dendritic computation. PMID:27009157

  11. DMPD: Heterogeneity of TLR-induced responses in dendritic cells: from innate toadaptive immunity. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15481153 Heterogeneity of TLR-induced responses in dendritic cells: from innate toadaptive...w Heterogeneity of TLR-induced responses in dendritic cells: from innate toadaptive immunity. PubmedID 15481...153 Title Heterogeneity of TLR-induced responses in dendritic cells: from innate toadaptive

  12. Influence of Dynamic Capabilities in Creating Disruptive Innovation

    OpenAIRE

    Čiutienė, R; Thattakath, E

    2015-01-01

    The aim of this paper is to demonstrate the influence of Dynamic Capabilities in creating Disruptive Innovation. For doing so the concepts of Dynamic Capabilities and Disruptive Innovation are reviewed. The criteria of an innovation named Disruptive Innovation are obtained by comparative study between the various innovation types. To demonstrate the role of Dynamic Capabilities in creating Disruptive Innovation, the Innovation Lifecycle is demonstrated with respect to Dynamic Capabilities. Th...

  13. Fungal tools for the degradation of endocrine disrupting compounds

    OpenAIRE

    Kabiersch, Grit

    2013-01-01

    Endocrine disrupting compounds are synthetic or natural compounds that mimic the action of hormones and thus disrupt or alter functions of the endocrine system usually through direct interactions with nuclear receptors. The main objective of this work was to develop strategies of how to degrade endocrine disrupting compounds and how to monitor the removal of the endocrine disrupting effect with focus on the estrogenic compound bisphenol A and on the virilizing compound tributyltin. Bisph...

  14. Fortum, how an incumbent should deal with a disruptive innovation

    OpenAIRE

    Noteboom, Arno

    2014-01-01

    Solar PV as a disruptive innovation is changing the established energy industry. It forces energy incumbents to compete on a new market, and on new features. This research sets out to investigate how Fortum should be dealing with this disruptive innovation. This study is conducted in two parts, first it is analysed what the effects are of solar PV being labelled disruptive. This determines whether Fortum should at all be participating in this new disruptive market. The second part analyse...

  15. Influence of Dynamic Capabilities in Creating Disruptive Innovation

    OpenAIRE

    Čiutienė, R; Thattakath, E

    2014-01-01

    The aim of this paper is to demonstrate the influence of Dynamic Capabilities in creating Disruptive Innovation. For doing so the concepts of Dynamic Capabilities and Disruptive Innovation are reviewed. The criteria of an innovation named Disruptive Innovation are obtained by comparative study between the various innovation types. To demonstrate the role of Dynamic Capabilities in creating Disruptive Innovation, the Innovation Lifecycle is demonstrated with respect to Dynamic Capabilities. Th...

  16. Extensor Mechanism Disruption in Knee Dislocation.

    Science.gov (United States)

    O'Malley, Michael; Reardon, Patrick; Pareek, Ayoosh; Krych, Aaron; Levy, Bruce A; Stuart, Michael J

    2016-05-01

    Disruption of the knee extensor mechanism is a challenging injury with no clear consensus on optimal treatment. Although rare in the setting of knee dislocations, these injuries should not be overlooked. Acute, complete rupture of either the quadriceps or patellar tendon necessitates primary repair with or without augmentation. Surgical management may also be required in the setting of a partial tear if a significant extensor lag is present or nonoperative treatment has failed. Tendon augmentation is used during primary repair if the native tissue is inadequate or after a failed primary repair. The purpose of this study is to evaluate extensor mechanism disruption incidence, injury patterns, associated injuries, and surgical options, including a novel tendon augmentation technique. This procedure consists of primary patellar or quadriceps tendon repair with semitendinosus autograft augmentation utilizing a distal or proximal patellar socket. Advantages of repair with tendon augmentation include accelerated rehabilitation, decreased risk of patellar fracture from transverse or longitudinal bone tunnels, and less hardware complications. We recommend consideration of this technique for selected cases of acute extensor mechanism disruption in the setting of tibiofemoral dislocation. PMID:26636488

  17. Risk Evaluation of Endocrine-Disrupting Chemicals

    Directory of Open Access Journals (Sweden)

    Laura Gioiosa

    2015-10-01

    Full Text Available We review here our studies on early exposure to low doses of the estrogenic endocrine-disrupting chemical bisphenol A (BPA on behavior and metabolism in CD-1 mice. Mice were exposed in utero from gestation day (GD 11 to delivery (prenatal exposure or via maternal milk from birth to postnatal day 7 (postnatal exposure to 10 µg/kg body weight/d of BPA or no BPA (controls. Bisphenol A exposure resulted in long-term disruption of sexually dimorphic behaviors. Females exposed to BPA pre- and postnatally showed increased anxiety and behavioral profiles similar to control males. We also evaluated metabolic effects in prenatally exposed adult male offspring of dams fed (from GD 9 to 18 with BPA at doses ranging from 5 to 50 000 µg/kg/d. The males showed an age-related significant change in a number of metabolic indexes ranging from food intake to glucose regulation at BPA doses below the no observed adverse effect level (5000 µg/kg/d. Consistent with prior findings, low but not high BPA doses produced significant effects for many outcomes. These findings provide further evidence of the potential risks that developmental exposure to low doses of the endocrine disrupter BPA may pose to human health, with fetuses and infants being highly vulnerable.

  18. Physician disruptive behaviors: Five year progress report.

    Science.gov (United States)

    Rosenstein, Alan H

    2015-11-16

    Disruptive behaviors in health care can have a significant adverse effect on staff interactions that can negatively impact staff satisfaction, staff performance, and patient outcomes of care. As referenced in a previously published article, the Obstetrics and Gynecology specialty is one of the service areas where these behaviors occur more frequently. Despite growing evidence of the ill effects of these types of behaviors many organizations are still having a difficult time in addressing these issues in an effective manner. Gaining a better understanding of the nature, causes, and impact of these behaviors is crucial to finding the right remedies for solution. Nobody intentionally starts the day planning to be disruptive, it's just that things get in the way. A combination of deep seated factors related to age and gender preferences, culture and ethnicity, life experiences, and other events that help shape values, attitudes and personalities, and more external factors related to training, environmental pressures, stress and burnout, and other personal issues all contribute to the mix. Given the complexities of today's health care environment, each person needs to recognize the importance of being held accountable for appropriate actions and behaviors that affect work relationships and care coordination that impact patient care. Early recognition, early intervention, and taking a pro-active supportive approach to improve individual behaviors will result in better relationships, less disruption, more satisfaction, and better outcomes of care. PMID:26601095

  19. Functional Role of Dendritic Cells in Patients with Unstable Angina

    Institute of Scientific and Technical Information of China (English)

    LI Dazhu; Sharma Ranjit; ZENG Qiutang

    2005-01-01

    To investigate the function of dendritic cells (DC) in patients with unstable angina, 10 mL of blood was drawn from 30 subjects. 15 patients diagnosed as having unstable angina and 15 healthy subjects were included in an observation and a control groups respectively. The mononuclear cells were separated from the peripheral blood and cultured in RPMI1640 supplemented with recombinant human granulocyte/macrophage-colony stimulating factor (rh GM-CSF) and recombinant human interleukin-4 (rh IL-4) to induce dendritic cells. The shape and ultrastructure of DC was examined with electronic microscope. The phenotype of DC was analyzed with FACS and the alloantigen presenting capacity of DC was evaluated by mixed lymphocyte reaction (MLR). The expression rate of CD86 of DC in patients with unstable angina was (40.7±3.6) %, which was obviously higher than that of normal DC (29.6±2.5 %) (P<0.001). The capacity of the DCs in unstable angina patients to induce allogenic T cells (OD 2.73±1.10), was significantly higher than that of the normal DC (OD:0.9±0.21) (P<0.005). It is suggested that the function of DC in patients with unstable angina is increased, which may play an important role in the initiation of immune reaction in the plaque.

  20. Superresolving dendritic spine morphology with STED microscopy under holographic photostimulation.

    Science.gov (United States)

    Lauterbach, Marcel Andreas; Guillon, Marc; Desnos, Claire; Khamsing, Dany; Jaffal, Zahra; Darchen, François; Emiliani, Valentina

    2016-10-01

    Emerging all-optical methods provide unique possibilities for noninvasive studies of physiological processes at the cellular and subcellular scale. On the one hand, superresolution microscopy enables observation of living samples with nanometer resolution. On the other hand, light can be used to stimulate cells due to the advent of optogenetics and photolyzable neurotransmitters. To exploit the full potential of optical stimulation, light must be delivered to specific cells or even parts of cells such as dendritic spines. This can be achieved with computer generated holography (CGH), which shapes light to arbitrary patterns by phase-only modulation. We demonstrate here in detail how CGH can be incorporated into a stimulated emission depletion (STED) microscope for photostimulation of neurons and monitoring of nanoscale morphological changes. We implement an original optical system to allow simultaneous holographic photostimulation and superresolution STED imaging. We present how synapses can be clearly visualized in live cells using membrane stains either with lipophilic organic dyes or with fluorescent proteins. We demonstrate the capabilities of this microscope to precisely monitor morphological changes of dendritic spines after stimulation. These all-optical methods for cell stimulation and monitoring are expected to spread to various fields of biological research in neuroscience and beyond. PMID:27413766

  1. Tumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Adriana J Michielsen

    Full Text Available Inflammatory mediators in the tumour microenvironment promote tumour growth, vascular development and enable evasion of anti-tumour immune responses, by disabling infiltrating dendritic cells. However, the constituents of the tumour microenvironment that directly influence dendritic cell maturation and function are not well characterised. Our aim was to identify tumour-associated inflammatory mediators which influence the function of dendritic cells. Tumour conditioned media obtained from cultured colorectal tumour explant tissue contained high levels of the chemokines CCL2, CXCL1, CXCL5 in addition to VEGF. Pre-treatment of monocyte derived dendritic cells with this tumour conditioned media inhibited the up-regulation of CD86, CD83, CD54 and HLA-DR in response to LPS, enhancing IL-10 while reducing IL-12p70 secretion. We examined if specific individual components of the tumour conditioned media (CCL2, CXCL1, CXCL5 could modulate dendritic cell maturation or cytokine secretion in response to LPS. VEGF was also assessed as it has a suppressive effect on dendritic cell maturation. Pre-treatment of immature dendritic cells with VEGF inhibited LPS induced upregulation of CD80 and CD54, while CXCL1 inhibited HLA-DR. Interestingly, treatment of dendritic cells with CCL2, CXCL1, CXCL5 or VEGF significantly suppressed their ability to secrete IL-12p70 in response to LPS. In addition, dendritic cells treated with a combination of CXCL1 and VEGF secreted less IL-12p70 in response to LPS compared to pre-treatment with either cytokine alone. In conclusion, tumour conditioned media strongly influences dendritic cell maturation and function.

  2. Tumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer.

    LENUS (Irish Health Repository)

    Michielsen, Adriana J

    2011-01-01

    Inflammatory mediators in the tumour microenvironment promote tumour growth, vascular development and enable evasion of anti-tumour immune responses, by disabling infiltrating dendritic cells. However, the constituents of the tumour microenvironment that directly influence dendritic cell maturation and function are not well characterised. Our aim was to identify tumour-associated inflammatory mediators which influence the function of dendritic cells. Tumour conditioned media obtained from cultured colorectal tumour explant tissue contained high levels of the chemokines CCL2, CXCL1, CXCL5 in addition to VEGF. Pre-treatment of monocyte derived dendritic cells with this tumour conditioned media inhibited the up-regulation of CD86, CD83, CD54 and HLA-DR in response to LPS, enhancing IL-10 while reducing IL-12p70 secretion. We examined if specific individual components of the tumour conditioned media (CCL2, CXCL1, CXCL5) could modulate dendritic cell maturation or cytokine secretion in response to LPS. VEGF was also assessed as it has a suppressive effect on dendritic cell maturation. Pre-treatment of immature dendritic cells with VEGF inhibited LPS induced upregulation of CD80 and CD54, while CXCL1 inhibited HLA-DR. Interestingly, treatment of dendritic cells with CCL2, CXCL1, CXCL5 or VEGF significantly suppressed their ability to secrete IL-12p70 in response to LPS. In addition, dendritic cells treated with a combination of CXCL1 and VEGF secreted less IL-12p70 in response to LPS compared to pre-treatment with either cytokine alone. In conclusion, tumour conditioned media strongly influences dendritic cell maturation and function.

  3. Dendritic branching of olfactory bulb mitral and tufted cells: regulation by TrkB.

    Directory of Open Access Journals (Sweden)

    Fumiaki Imamura

    Full Text Available BACKGROUND: Projection neurons of mammalian olfactory bulb (OB, mitral and tufted cells, have dendrites whose morphologies are specifically differentiated for efficient odor information processing. The apical dendrite extends radially and arborizes in single glomerulus where it receives primary input from olfactory sensory neurons that express the same odor receptor. The lateral dendrites extend horizontally in the external plexiform layer and make reciprocal dendrodendritic synapses with granule cells, which moderate mitral/tufted cell activity. The molecular mechanisms regulating dendritic development of mitral/tufted cells is one of the unsolved important problems in the olfactory system. Here, we focused on TrkB receptors to test the hypothesis that neurotrophin-mediate mechanisms contributed to dendritic differentiation of OB mitral/tufted cells. PRINCIPAL FINDINGS: With immunohistochemical analysis, we found that the TrkB neurotrophin receptor is expressed by both apical and lateral dendrites of mitral/tufted cells and that expression is evident during the early postnatal days when these dendrites exhibit their most robust growth and differentiation. To examine the effect of TrkB activation on mitral/tufted cell dendritic development, we cultured OB neurons. When BDNF or NT4 were introduced into the cultures, there was a significant increase in the number of primary neurites and branching points among the mitral/tufted cells. Moreover, BDNF facilitated filopodial extension along the neurites of mitral/tufted cells. SIGNIFICANCE: In this report, we show for the first time that TrkB activation stimulates the dendritic branching of mitral/tufted cells in developing OB. This suggests that arborization of the apical dendrite in a glomerulus is under the tight regulation of TrkB activation.

  4. Disruptive Behaviour of Students in Primary Education and Emotional Intelligence

    Science.gov (United States)

    Esturgo-Deu, M. Estrella; Sala-Roca, Josefina

    2010-01-01

    This study analyses the relation between disruptive behaviours and the emotional abilities of children in primary education. To do this, disruptive behaviour and emotional abilities were evaluated in 1422 pupils aged between 6 and 12 years of age at 11 education centres using EQIjv. No relation was found between disruptive behaviours and age, but…

  5. The Impact of Marital Conflict and Disruption on Children's Health

    Science.gov (United States)

    Houseknecht, Sharon K.; Hango, Darcy W.

    2006-01-01

    This article investigates the effect of inconsistency between parental marital conflict and disruption on children's health. Inconsistent situations arise when minimal marital conflict precedes disruption or when marital conflict is high but there is no disruption. Using data from the National Longitudinal Survey of Youth, two alternative…

  6. A New Criterion for Disruption Prediction on HL-2A

    Institute of Scientific and Technical Information of China (English)

    YANG Qing-Wei; JI Xiao-Quan; DING Xuan-Tong; HL-2A team; ZHOU Hang-Yu; FENG Bei-Bin; LIU Yi; PAN Yu-Dong; LI Wei; DUAN Xu-Ru; CHEN Wei; CUI Zheng-Ying

    2006-01-01

    @@ A new criterion has been proposed to predict the major disruptions caused by tearing mode instabilities. According to the HL-2A experimental results, the statistical analyses are employed to investigate the relationships between MHD activities and the plasma disruptions. Two kinds of the tearing mode activities can finally cause the disruption on HL-2A operations. By introducing a new parameter, i.e. an integral of poloidal magnetic field over time, as the criterion of disruption precursor, almost all of the disruptions can be predicted.

  7. Tidal disruption events from supermassive black hole binaries

    CERN Document Server

    Coughlin, Eric R; Nixon, Chris; Begelman, Mitchell C

    2016-01-01

    We investigate the pre-disruption gravitational dynamics and post-disruption hydrodynamics of the tidal disruption of stars by supermassive black hole (SMBH) binaries. We focus on binaries with relatively low mass primaries ($10^6M_{\\odot}$), moderate mass ratios, and separations with reasonably long gravitational wave inspiral times (tens of Myr). First, we generate a large ensemble (between 1 and 10 million) of restricted three-body integrations to quantify the statistical properties of tidal disruptions by circular SMBH binaries of initially-unbound stars. Compared to the reference case of a disruption by a single SMBH, the binary potential induces significant variance into the specific energy and angular momentum of the star at the point of disruption. Second, we use Newtonian numerical hydrodynamics to study the detailed evolution of the fallback debris from 120 disruptions randomly selected from the three-body ensemble (excluding only the most deeply penetrating encounters). We find that the overall mor...

  8. Inorganic arsenic impairs differentiation and functions of human dendritic cells

    Energy Technology Data Exchange (ETDEWEB)

    Macoch, Mélinda; Morzadec, Claudie [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France); Fardel, Olivier [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France); Pôle Biologie, Centre Hospitalier Universitaire (CHU) Rennes, 2 rue Henri Le Guilloux, 35033 Rennes (France); Vernhet, Laurent, E-mail: laurent.vernhet@univ-rennes1.fr [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France)

    2013-01-15

    Experimental studies have demonstrated that the antileukemic trivalent inorganic arsenic prevents the development of severe pro-inflammatory diseases mediated by excessive Th1 and Th17 cell responses. Differentiation of Th1 and Th17 subsets is mainly regulated by interleukins (ILs) secreted from dendritic cells (DCs) and the ability of inorganic arsenic to impair interferon-γ and IL-17 secretion by interfering with the physiology of DCs is unknown. In the present study, we demonstrate that high concentrations of sodium arsenite (As(III), 1–2 μM) clinically achievable in plasma of arsenic-treated patients, block differentiation of human peripheral blood monocytes into immature DCs (iDCs) by inducing their necrosis. Differentiation of monocytes in the presence of non-cytotoxic concentrations of As(III) (0.1 to 0.5 μM) only slightly impacts endocytotic activity of iDCs or expression of co-stimulatory molecules in cells activated with lipopolysaccharide. However, this differentiation in the presence of As(III) strongly represses secretion of IL-12p70 and IL-23, two major regulators of Th1 and Th17 activities, from iDCs stimulated with different toll-like receptor (TLR) agonists in metalloid-free medium. Such As(III)-exposed DCs also exhibit reduced mRNA levels of IL12A and/or IL12B genes when activated with TLR agonists. Finally, differentiation of monocytes with non-cytotoxic concentrations of As(III) subsequently reduces the ability of activated DCs to stimulate the release of interferon-γ and IL-17 from Th cells. In conclusion, our results demonstrate that clinically relevant concentrations of inorganic arsenic markedly impair in vitro differentiation and functions of DCs, which may contribute to the putative beneficial effects of the metalloid towards inflammatory autoimmune diseases. Highlights: ► Inorganic arsenic impairs differentiation and functions of human dendritic cells (DCs) ► Arsenite (> 1 μM) blocks differentiation of dendritic cells by

  9. Modulation of dendritic cell function by Trichomonas vaginalis-derived secretory products.

    Science.gov (United States)

    Song, Min-Ji; Lee, Jong-Joo; Nam, Young Hee; Kim, Tae-Gyun; Chung, Youn Wook; Kim, Mikyoung; Choi, Ye-Eun; Shin, Myeong Heon; Kim, Hyoung-Pyo

    2015-02-01

    Trichomoniasis caused by the parasitic protozoan Trichomonas vaginalis is the most common sexually transmitted disease in the world. Dendritic cells are antigen presenting cells that initiate immune responses by directing the activation and differentiation of naïve T cells. In this study, we analyzed the effect of Trichomonas vaginalis-derived Secretory Products on the differentiation and function of dendritic cells. Differentiation of bone marrow-derived dendritic cells in the presence of T. vaginalis-derived Secretory Products resulted in inhibition of lipopolysaccharide-induced maturation of dendritic cells, down-regulation of IL-12, and up-regulation of IL-10. The protein components of T. vaginalis-derived Secretory Products were shown to be responsible for altered function of bone marrow- derived dendritic cells. Chromatin immunoprecipitation assay demonstrated that IL-12 expression was regulated at the chromatin level in T. vaginalis-derived Secretory Productstreated dendritic cells. Our results demonstrated that T. vaginalis- derived Secretory Products modulate the maturation and cytokine production of dendritic cells leading to immune tolerance.

  10. Effect of sample diameter on primary dendrite spacing of directionally solidified Al-4%Cu alloy

    Institute of Scientific and Technical Information of China (English)

    QU Min; LIU Lin; TANG Feng-tao; ZHANG Jun; FU Heng-zhi

    2009-01-01

    The relationship between primary dendrite arm spacing and sample diameter was studied during directional solidification for Al-4%Cu (mass fraction) alloy. It is shown that primary dendrite spacing is decreased with the decrease of the sample diameter at given growth rate. By regressing the relationship between primary dendrite arm spacing and the growth rate, the primary dendrite arm spacing complies with 461.76v-0.53, 417.92v-0.28 and 415.83v-0.25 for the sample diameter of 1.8, 3.5 and 7.2 mm, respectively. The primary dendrite spacing, growth rate and thermal gradient for different sample diameters comply with 28.77v-0.35G-0.70, 23.17v-0.35G-0.70 and 23.84v-0.35G-0.70, respectively. They are all consistent with the theoretical model , and b1/a1=2. By analyzing the experimental results with classical models, it is shown that KURZ-FISHER model fits for the primary dendrite spacing in smaller sample diameters with weaker thermosolute convection. Whereas TRIVEDI model is suitable for describing primary dendrite arm spacing with a larger diameter (d>2 mm) where convection should be considered.

  11. Three-Step Model for Polarized Sorting of KIF17 into Dendrites.

    Science.gov (United States)

    Franker, Mariella A; Esteves da Silva, Marta; Tas, Roderick P; Tortosa, Elena; Cao, Yujie; Frias, Cátia P; Janssen, Anne F J; Wulf, Phebe S; Kapitein, Lukas C; Hoogenraad, Casper C

    2016-07-11

    Kinesin and dynein motors drive bidirectional cargo transport along microtubules and have a critical role in polarized cargo trafficking in neurons [1, 2]. The kinesin-2 family protein KIF17 is a dendrite-specific motor protein and has been shown to interact with several dendritic cargoes [3-7]. However, the mechanism underlying the dendritic targeting of KIF17 remains poorly understood [8-11]. Using live-cell imaging combined with inducible trafficking assays to directly probe KIF17 motor activity in living neurons, we found that the polarized sorting of KIF17 to dendrites is regulated in multiple steps. First, cargo binding of KIF17 relieves autoinhibition and initiates microtubule-based cargo transport. Second, KIF17 does not autonomously target dendrites, but enters the axon where the actin cytoskeleton at the axon initial segment (AIS) prevents KIF17 vesicles from moving further into the axon. Third, dynein-based motor activity is able to redirect KIF17-coupled cargoes into dendrites. We propose a three-step model for polarized targeting of KIF17, in which the collective function of multiple motor teams is required for proper dendritic sorting. PMID:27265394

  12. Effects of GSM 1800 MHz on dendritic development of cultured hippo-campal neurons

    Institute of Scientific and Technical Information of China (English)

    Wei NING; Shu-jun XU; Huai CHIANG; Zheng-ping XU; Su-ya ZHOU; Wei YANG; Jian-hong LUO

    2007-01-01

    Aim: To evaluate the effects of global system for mobile communications (GSM)1800 MHz microwaves on dendritic filopodia, dendritic arborization, and spine maturation during development in cultured hippocampal neurons in rats. Methods: The cultured hippocampal neurons were exposed to GSM 1800 MHz microwaves with 2.4 and 0.8 W/kg, respectively, for 15 min each day from 6 days in vitro (DIV6) to DIV14. The subtle structures of dendrites were displayed by transfection with farnesylated enhanced green fluorescent protein (F-GFP) and GFP-actin on DIV5 into the hippocampal neurons. Results: There was a significant decrease in the density and mobility of dendritic filopodia at DIV8 and in the density of mature spines at DIV14 in the neurons exposed to GSM 1800 MHz microwaves with 2.4 W/kg. In addition, the average length of dendrites per neuron at DIV10 and DIV14 was decreased, while the dendritic arborization was unaltered in these neurons. However, there were no significant changes found in the neurons ex- posed to the GSM 1800 MHz microwaves with 0.8 W/kg. Conclusion: These data indicate that the chronic exposure to 2.4 W/kg GSM 1800 MHz micro- waves during the early developmental stage may affect dendritic development and the formation of excitatory synapses of hippocampal neurons in culture.

  13. Spike-Timing–Dependent Synaptic Plasticity and Synaptic Democracy in Dendrites

    Science.gov (United States)

    Gidon, Albert; Segev, Idan

    2009-01-01

    We explored in a computational study the effect of dendrites on excitatory synapses undergoing spike-timing–dependent plasticity (STDP), using both cylindrical dendritic models and reconstructed dendritic trees. We show that even if the initial strength, gpeak, of distal synapses is augmented in a location independent manner, the efficacy of distal synapses diminishes following STDP and proximal synapses would eventually dominate. Indeed, proximal synapses always win over distal synapses following linear STDP rule, independent of the initial synaptic strength distribution in the dendritic tree. This effect is more pronounced as the dendritic cable length increases but it does not depend on the dendritic branching structure. Adding a small multiplicative component to the linear STDP rule, whereby already strong synapses tend to be less potentiated than depressed (and vice versa for weak synapses) did partially “save” distal synapses from “dying out.” Another successful strategy for balancing the efficacy of distal and proximal synapses following STDP is to increase the upper bound for the synaptic conductance (gmax) with distance from the soma. We conclude by discussing an experiment for assessing which of these possible strategies might actually operate in dendrites. PMID:19357339

  14. Spike-timing-dependent synaptic plasticity and synaptic democracy in dendrites.

    Science.gov (United States)

    Gidon, Albert; Segev, Idan

    2009-06-01

    We explored in a computational study the effect of dendrites on excitatory synapses undergoing spike-timing-dependent plasticity (STDP), using both cylindrical dendritic models and reconstructed dendritic trees. We show that even if the initial strength, g(peak), of distal synapses is augmented in a location independent manner, the efficacy of distal synapses diminishes following STDP and proximal synapses would eventually dominate. Indeed, proximal synapses always win over distal synapses following linear STDP rule, independent of the initial synaptic strength distribution in the dendritic tree. This effect is more pronounced as the dendritic cable length increases but it does not depend on the dendritic branching structure. Adding a small multiplicative component to the linear STDP rule, whereby already strong synapses tend to be less potentiated than depressed (and vice versa for weak synapses) did partially "save" distal synapses from "dying out." Another successful strategy for balancing the efficacy of distal and proximal synapses following STDP is to increase the upper bound for the synaptic conductance (g(max)) with distance from the soma. We conclude by discussing an experiment for assessing which of these possible strategies might actually operate in dendrites.

  15. Spines slow down dendritic chloride diffusion and affect short-term ionic plasticity of GABAergic inhibition

    Science.gov (United States)

    Mohapatra, Namrata; Tønnesen, Jan; Vlachos, Andreas; Kuner, Thomas; Deller, Thomas; Nägerl, U. Valentin; Santamaria, Fidel; Jedlicka, Peter

    2016-03-01

    Cl‑ plays a crucial role in neuronal function and synaptic inhibition. However, the impact of neuronal morphology on the diffusion and redistribution of intracellular Cl‑ is not well understood. The role of spines in Cl‑ diffusion along dendritic trees has not been addressed so far. Because measuring fast and spatially restricted Cl‑ changes within dendrites is not yet technically possible, we used computational approaches to predict the effects of spines on Cl‑ dynamics in morphologically complex dendrites. In all morphologies tested, including dendrites imaged by super-resolution STED microscopy in live brain tissue, spines slowed down longitudinal Cl‑ diffusion along dendrites. This effect was robust and could be observed in both deterministic as well as stochastic simulations. Cl‑ extrusion altered Cl‑ diffusion to a much lesser extent than the presence of spines. The spine-dependent slowing of Cl‑ diffusion affected the amount and spatial spread of changes in the GABA reversal potential thereby altering homosynaptic as well as heterosynaptic short-term ionic plasticity at GABAergic synapses in dendrites. Altogether, our results suggest a fundamental role of dendritic spines in shaping Cl‑ diffusion, which could be of relevance in the context of pathological conditions where spine densities and neural excitability are perturbed.

  16. Dendritic Pt-Cu bimetallic nanocrystals with a high electrocatalytic activity toward methanol oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Jintao; Ma Jizhen [Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117576 (Singapore); Wan Yong [Institute of Multifunctional Materials (IMM), Laboratory of New Fiber Materials and Modern Textile, Growing Base for State Key Laboratory, Qingdao University, Qingdao 266071 (China); Jiang Jianwen [Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117576 (Singapore); Zhao, X.S., E-mail: george.zhao@uq.edu.au [Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117576 (Singapore); Institute of Multifunctional Materials (IMM), Laboratory of New Fiber Materials and Modern Textile, Growing Base for State Key Laboratory, Qingdao University, Qingdao 266071 (China)

    2012-02-15

    Highlights: Black-Right-Pointing-Pointer Dendritic Pt-Cu bimetallic nanocrystals were synthesized by one-step aqueous-phase reduction. Black-Right-Pointing-Pointer The formation process of dendritic Pt-Cu bimetallic nanocrystals can be carried out under mild conditions. Black-Right-Pointing-Pointer The dendritic Pt-Cu bimetallic nanocrystals exhibited a higher catalytic activity toward the electro-oxidation of methanol than commercial Pt/C catalysts. Black-Right-Pointing-Pointer The new findings are of fundamental importance to the development of high-performance electrocatalysts for direct methanol fuel cell. - Abstract: Dendritic Pt-Cu bimetallic nanocrystals were synthesized by one-step aqueous-phase reduction of H{sub 2}PtCl{sub 6} and CuCl{sub 2} at a mild temperature (60 Degree-Sign C). The morphology and composition of the dendritic Pt-Cu nanocrystals were characterized by means of high-resolution transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and energy dispersive X-ray spectrometer. The electrochemical properties were characterized by the cyclic voltammetry technique. It was found that the dendritic Pt-Cu bimetallic nanocrystals exhibited a higher catalytic activity toward the electro-oxidation of methanol than commercial Pt/C catalyst The enhanced catalytic activity would be contributed to the unique dendritic structure and the formation of Pt-Cu alloy nanocrystals.

  17. Drosophila Hook-Related Protein (Girdin) Is Essential for Sensory Dendrite Formation.

    Science.gov (United States)

    Ha, Andrew; Polyanovsky, Andrey; Avidor-Reiss, Tomer

    2015-08-01

    The dendrite of the sensory neuron is surrounded by support cells and is composed of two specialized compartments: the inner segment and the sensory cilium. How the sensory dendrite is formed and maintained is not well understood. Hook-related proteins (HkRP) like Girdin, DAPLE, and Gipie are actin-binding proteins, implicated in actin organization and in cell motility. Here, we show that the Drosophila melanogaster single member of the Hook-related protein family, Girdin, is essential for sensory dendrite formation and function. Mutations in girdin were identified during a screen for fly mutants with no mechanosensory function. Physiological, morphological, and ultrastructural studies of girdin mutant flies indicate that the mechanosensory neurons innervating external sensory organs (bristles) initially form a ciliated dendrite that degenerates shortly after, followed by the clustering of their cell bodies. Importantly, we observed that Girdin is expressed transiently during dendrite morphogenesis in three previously unidentified actin-based structures surrounding the inner segment tip and the sensory cilium. These actin structures are largely missing in girdin mutant. Defects in cilia are observed in other sensory organs such as those mediating olfaction and taste, suggesting that Girdin has a general role in forming sensory dendrites in Drosophila. These suggest that Girdin functions temporarily within the sensory organ and that this function is essential for the formation of the sensory dendrites via actin structures.

  18. Dendrite architecture organized by transcriptional control of the F-actin nucleator Spire.

    Science.gov (United States)

    Ferreira, Tiago; Ou, Yimiao; Li, Sally; Giniger, Edward; van Meyel, Donald J

    2014-02-01

    The architectures of dendritic trees are crucial for the wiring and function of neuronal circuits because they determine coverage of receptive territories, as well as the nature and strength of sensory or synaptic inputs. Here, we describe a cell-intrinsic pathway sculpting dendritic arborization (da) neurons in Drosophila that requires Longitudinals Lacking (Lola), a BTB/POZ transcription factor, and its control of the F-actin cytoskeleton through Spire (Spir), an actin nucleation protein. Loss of Lola from da neurons reduced the overall length of dendritic arbors, increased the expression of Spir, and produced inappropriate F-actin-rich dendrites at positions too near the cell soma. Selective removal of Lola from only class IV da neurons decreased the evasive responses of larvae to nociception. The increased Spir expression contributed to the abnormal F-actin-rich dendrites and the decreased nocifensive responses because both were suppressed by reduced dose of Spir. Thus, an important role of Lola is to limit expression of Spir to appropriate levels within da neurons. We found Spir to be expressed in dendritic arbors and to be important for their development. Removal of Spir from class IV da neurons reduced F-actin levels and total branch number, shifted the position of greatest branch density away from the cell soma, and compromised nocifensive behavior. We conclude that the Lola-Spir pathway is crucial for the spatial arrangement of branches within dendritic trees and for neural circuit function because it provides balanced control of the F-actin cytoskeleton.

  19. ApoE receptor 2 regulates synapse and dendritic spine formation.

    Directory of Open Access Journals (Sweden)

    Sonya B Dumanis

    Full Text Available BACKGROUND: Apolipoprotein E receptor 2 (ApoEr2 is a postsynaptic protein involved in long-term potentiation (LTP, learning, and memory through unknown mechanisms. We examined the biological effects of ApoEr2 on synapse and dendritic spine formation-processes critical for learning and memory. METHODOLOGY/PRINCIPAL FINDINGS: In a heterologous co-culture synapse assay, overexpression of ApoEr2 in COS7 cells significantly increased colocalization with synaptophysin in primary hippocampal neurons, suggesting that ApoEr2 promotes interaction with presynaptic structures. In primary neuronal cultures, overexpression of ApoEr2 increased dendritic spine density. Consistent with our in vitro findings, ApoEr2 knockout mice had decreased dendritic spine density in cortical layers II/III at 1 month of age. We also tested whether the interaction between ApoEr2 and its cytoplasmic adaptor proteins, specifically X11α and PSD-95, affected synapse and dendritic spine formation. X11α decreased cell surface levels of ApoEr2 along with synapse and dendritic spine density. In contrast, PSD-95 increased cell surface levels of ApoEr2 as well as synapse and dendritic spine density. CONCLUSIONS/SIGNIFICANCE: These results suggest that ApoEr2 plays important roles in structure and function of CNS synapses and dendritic spines, and that these roles are modulated by cytoplasmic adaptor proteins X11α and PSD-95.

  20. Can ID repetitive elements serve as cis-acting dendritic targeting elements? An in vivo study.

    Directory of Open Access Journals (Sweden)

    Tasneem Khanam

    Full Text Available Dendritic localization of mRNA/RNA involves interaction of cis-elements and trans-factors. Small, non-protein coding dendritic BC1 RNA is thought to regulate translation in dendritic microdomains. Following microinjections into cultured cells, BC1 RNA fused to larger mRNAs appeared to impart transport competence to these chimeras, and its 5' ID region was proposed as the cis-acting dendritic targeting element. As these ID elements move around rodent genomes and, if transcribed, form a long RNA stem-loop, they might, thereby, lead to new localizations for targeted gene products. To test their targeting ability in vivo we created transgenic mice expressing various ID elements fused to the 3' UTR of reporter mRNA for Enhanced Green Fluorescent Protein. In vivo, neither ID elements nor the BC1 RNA coding region were capable of transporting EGFP RNA to dendrites, although the 3' UTR of alpha-CaMKII mRNA, an established cis-acting element did produce positive results. Other mRNAs containing naturally inserted ID elements are also not found in neuronal dendrites. We conclude that the 5' ID domain from BC1 RNA is not a sufficient dendritic targeting element for mRNAs in vivo.