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Sample records for localised cdc42 activity

  1. Mechanism of IRSp53 inhibition and combinatorial activation by Cdc42 and downstream effectors.

    Science.gov (United States)

    Kast, David J; Yang, Changsong; Disanza, Andrea; Boczkowska, Malgorzata; Madasu, Yadaiah; Scita, Giorgio; Svitkina, Tatyana; Dominguez, Roberto

    2014-04-01

    The Rho family GTPase effector IRSp53 has essential roles in filopodia formation and neuronal development, but its regulatory mechanism is poorly understood. IRSp53 contains a membrane-binding BAR domain followed by an unconventional CRIB motif that overlaps with a proline-rich region (CRIB-PR) and an SH3 domain that recruits actin cytoskeleton effectors. Using a fluorescence reporter assay, we show that human IRSp53 adopts a closed inactive conformation that opens synergistically with the binding of human Cdc42 to the CRIB-PR and effector proteins, such as the tumor-promoting factor Eps8, to the SH3 domain. The crystal structure of Cdc42 bound to the CRIB-PR reveals a new mode of effector binding to Rho family GTPases. Structure-inspired mutations disrupt autoinhibition and Cdc42 binding in vitro and decouple Cdc42- and IRSp53-dependent filopodia formation in cells. The data support a combinatorial mechanism of IRSp53 activation.

  2. Cdc42-dependent actin dynamics controls maturation and secretory activity of dendritic cells

    DEFF Research Database (Denmark)

    Schulz, Anna M; Stutte, Susanne; Hogl, Sebastian

    2015-01-01

    Cell division cycle 42 (Cdc42) is a member of the Rho guanosine triphosphatase family and has pivotal functions in actin organization, cell migration, and proliferation. To further study the molecular mechanisms of dendritic cell (DC) regulation by Cdc42, we used Cdc42-deficient DCs. Cdc42 defici...

  3. Inhibition of Cdc42 and Rac1 activities in pheochromocytoma, the adrenal medulla tumor.

    Science.gov (United States)

    Croisé, Pauline; Brunaud, Laurent; Tóth, Petra; Gasman, Stéphane; Ory, Stéphane

    2017-04-03

    Altered Rho GTPase signaling has been linked to many types of cancer. As many small G proteins, Rho GTPases cycle between an active and inactive state thanks to specific regulators that catalyze exchange of GDP into GTP (Rho-GEF) or hydrolysis of GTP into GDP (Rho-GAP). Recent studies have shown that alteration takes place either at the level of Rho proteins themselves (expression levels, point mutations) or at the level of their regulators, mostly RhoGEFs and RhoGAPs. Most reports describe Rho GTPases gain of function that may participate to the tumorigenesis processes. In contrast, we have recently reported that decreased activities of Cdc42 and Rac1 as well as decreased expression of 2 Rho-GEFs, FARP1 and ARHGEF1, correlate with pheochromocytomas, a tumor developing in the medulla of the adrenal gland (Croisé et al., Endocrine Related Cancer, 2016). Here we highlight the major evidence and further study the correlation between Rho GTPases activities and expression levels of ARHGEF1 and FARP1. Finally we also discuss how the decrease of Cdc42 and Rac1 activities may help human pheochromocytomas to develop and comment the possible relationship between FARP1, ARHGEF1 and the 2 Rho GTPases Cdc42 and Rac1 in tumorigenesis.

  4. Novel Activities of Select NSAID R-Enantiomers against Rac1 and Cdc42 GTPases.

    Directory of Open Access Journals (Sweden)

    Tudor I Oprea

    Full Text Available Rho family GTPases (including Rac, Rho and Cdc42 collectively control cell proliferation, adhesion and migration and are of interest as functional therapeutic targets in numerous epithelial cancers. Based on high throughput screening of the Prestwick Chemical Library® and cheminformatics we identified the R-enantiomers of two approved drugs (naproxen and ketorolac as inhibitors of Rac1 and Cdc42. The corresponding S-enantiomers are considered the active component in racemic drug formulations, acting as non-steroidal anti-inflammatory drugs (NSAIDs with selective activity against cyclooxygenases. Here, we show that the S-enantiomers of naproxen and ketorolac are inactive against the GTPases. Additionally, more than twenty other NSAIDs lacked inhibitory action against the GTPases, establishing the selectivity of the two identified NSAIDs. R-naproxen was first identified as a lead compound and tested in parallel with its S-enantiomer and the non-chiral 6-methoxy-naphthalene acetic acid (active metabolite of nabumetone, another NSAID as a structural series. Cheminformatics-based substructure analyses-using the rotationally constrained carboxylate in R-naproxen-led to identification of racemic [R/S] ketorolac as a suitable FDA-approved candidate. Cell based measurement of GTPase activity (in animal and human cell lines demonstrated that the R-enantiomers specifically inhibit epidermal growth factor stimulated Rac1 and Cdc42 activation. The GTPase inhibitory effects of the R-enantiomers in cells largely mimic those of established Rac1 (NSC23766 and Cdc42 (CID2950007/ML141 specific inhibitors. Docking predicts that rotational constraints position the carboxylate moieties of the R-enantiomers to preferentially coordinate the magnesium ion, thereby destabilizing nucleotide binding to Rac1 and Cdc42. The S-enantiomers can be docked but are less favorably positioned in proximity to the magnesium. R-naproxen and R-ketorolac have potential for rapid

  5. Microgravity simulation activates Cdc42 via Rap1GDS1 to promote vascular branch morphogenesis during vasculogenesis

    Directory of Open Access Journals (Sweden)

    Shouli Wang

    2017-12-01

    Full Text Available Gravity plays an important role in normal tissue maintenance. The ability of stem cells to repair tissue loss in space through regeneration and differentiation remains largely unknown. To investigate the impact of microgravity on blood vessel formation from pluripotent stem cells, we employed the embryoid body (EB model for vasculogenesis and simulated microgravity by clinorotation. We first differentiated mouse embryonic stem cells into cystic EBs containing two germ layers and then analyzed vessel formation under clinorotation. We observed that endothelial cell differentiation was slightly reduced under clinorotation, whereas vascular branch morphogenesis was markedly enhanced. EB-derived endothelial cells migrated faster, displayed multiple cellular processes, and had higher Cdc42 and Rac1 activity when subjected to clinorotation. Genetic analysis and rescue experiments demonstrated that Cdc42 but not Rac1 is required for microgravity-induced vascular branch morphogenesis. Furthermore, affinity pull-down assay and mass spectrometry identified Rap1GDS1 to be a Cdc42 guanine nucleotide exchange factor, which was upregulated by clinorotation. shRNA-mediated knockdown of Rap1GDS1 selectively suppressed Cdc42 activation and inhibited both baseline and microgravity-induced vasculogenesis. This was rescued by ectopic expression of constitutively active Cdc42. Taken together, these results support the notion that simulated microgravity activates Cdc42 via Rap1GDS1 to promote vascular branch morphogenesis.

  6. Phosphatidylserine and GTPase activation control Cdc42 nanoclustering to counter dissipative diffusion.

    Science.gov (United States)

    Sartorel, Elodie; Ünlü, Caner; Jose, Mini; Massoni-Laporte, Aurélie; Meca, Julien; Sibarita, Jean-Baptiste; McCusker, Derek

    2018-04-18

    The anisotropic organization of plasma membrane constituents is indicative of mechanisms that drive the membrane away from equilibrium. However, defining these mechanisms is challenging due to the short spatio-temporal scales at which diffusion operates. Here, we use high-density single protein tracking combined with photoactivation localization microscopy (sptPALM) to monitor Cdc42 in budding yeast, a system in which Cdc42 exhibits anisotropic organization. Cdc42 exhibited reduced mobility at the cell pole, where it was organized in nanoclusters. The Cdc42 nanoclusters were larger at the cell pole than those observed elsewhere in the cell. These features were exacerbated in cells expressing Cdc42-GTP, and were dependent on the scaffold Bem1, which contributed to the range of mobility and nanocluster size exhibited by Cdc42. The lipid environment, in particular phosphatidylserine levels, also played a role in regulating Cdc42 nanoclustering. These studies reveal how the mobility of a Rho GTPase is controlled to counter the depletive effects of diffusion, thus stabilizing Cdc42 on the plasma membrane and sustaining cell polarity. Movie S1 Movie S1 sptPALM imaging of live yeast expressing Pil1-mEOS expressed at the genomic locus. Pil1-mEOS was simultaneously photo-converted with a 405 nm laser and imaged with a 561 nm laser using HiLo illumination. Images were acquired at 20 ms intervals, of which 300 frames are shown at 7 frames per second.

  7. Plexin-B2 negatively regulates macrophage motility, Rac, and Cdc42 activation.

    Directory of Open Access Journals (Sweden)

    Kelly E Roney

    Full Text Available Plexins are cell surface receptors widely studied in the nervous system, where they mediate migration and morphogenesis though the Rho family of small GTPases. More recently, plexins have been implicated in immune processes including cell-cell interaction, immune activation, migration, and cytokine production. Plexin-B2 facilitates ligand induced cell guidance and migration in the nervous system, and induces cytoskeletal changes in overexpression assays through RhoGTPase. The function of Plexin-B2 in the immune system is unknown. This report shows that Plexin-B2 is highly expressed on cells of the innate immune system in the mouse, including macrophages, conventional dendritic cells, and plasmacytoid dendritic cells. However, Plexin-B2 does not appear to regulate the production of proinflammatory cytokines, phagocytosis of a variety of targets, or directional migration towards chemoattractants or extracellular matrix in mouse macrophages. Instead, Plxnb2(-/- macrophages have greater cellular motility than wild type in the unstimulated state that is accompanied by more active, GTP-bound Rac and Cdc42. Additionally, Plxnb2(-/- macrophages demonstrate faster in vitro wound closure activity. Studies have shown that a closely related family member, Plexin-B1, binds to active Rac and sequesters it from downstream signaling. The interaction of Plexin-B2 with Rac has only been previously confirmed in yeast and bacterial overexpression assays. The data presented here show that Plexin-B2 functions in mouse macrophages as a negative regulator of the GTPases Rac and Cdc42 and as a negative regulator of basal cell motility and wound healing.

  8. Activated Cdc42 kinase regulates Dock localization in male germ cells during Drosophila spermatogenesis.

    Science.gov (United States)

    Abdallah, Abbas M; Zhou, Xin; Kim, Christine; Shah, Kushani K; Hogden, Christopher; Schoenherr, Jessica A; Clemens, James C; Chang, Henry C

    2013-06-15

    Deregulation of the non-receptor tyrosine kinase ACK1 (Activated Cdc42-associated kinase) correlates with poor prognosis in cancers and has been implicated in promoting metastasis. To further understand its in vivo function, we have characterized the developmental defects of a null mutation in Drosophila Ack, which bears a high degree of sequence similarity to mammalian ACK1 but lacks a CRIB domain. We show that Ack, while not essential for viability, is critical for sperm formation. This function depends on Ack tyrosine kinase activity and is required cell autonomously in differentiating male germ cells at or after the spermatocyte stage. Ack associates predominantly with endocytic clathrin sites in spermatocytes, but disruption of Ack function has no apparent effect on clathrin localization and receptor-mediated internalization of Boss (Bride of sevenless) protein in eye discs. Instead, Ack is required for the subcellular distribution of Dock (dreadlocks), the Drosophila homolog of the SH2- and SH3-containing adaptor protein Nck. Moreover, Dock forms a complex with Ack, and the localization of Dock in male germ cells depends on its SH2 domain. Together, our results suggest that Ack-dependent tyrosine phosphorylation recruits Dock to promote sperm differentiation. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Leucine-rich repeat kinase-1 regulates osteoclast function by modulating RAC1/Cdc42 Small GTPase phosphorylation and activation.

    Science.gov (United States)

    Zeng, Canjun; Goodluck, Helen; Qin, Xuezhong; Liu, Bo; Mohan, Subburaman; Xing, Weirong

    2016-10-01

    Leucine-rich repeat kinase-1 (Lrrk1) consists of ankyrin repeats (ANK), leucine-rich repeats (LRR), a GTPase-like domain of Roc (ROC), a COR domain, a serine/threonine kinase domain (KD), and WD40 repeats (WD40). Previous studies have revealed that knockout (KO) of Lrrk1 in mice causes severe osteopetrosis, and a human mutation of Lrrk1 leads to osteosclerotic metaphysial dysplasia. The molecular mechanism by which Lrrk1 regulates osteoclast function is unknown. In this study, we generated a series of Lrrk1 mutants and evaluated their ability to rescue defective bone resorption in Lrrk1-deficient osteoclasts by use of pit formation assays. Overexpression of Lrrk1 or LRR-truncated Lrrk1, but not ANK-truncated Lrrk1, WD40-truncated Lrrk1, Lrrk1-KD, or K651A mutant Lrrk1, rescued bone resorption function of Lrrk1 KO osteoclasts. We next examined whether RAC1/Cdc42 small GTPases are direct substrates of Lrrk1 in osteoclasts. Western blot and pull-down assays revealed that Lrrk1 deficiency in osteoclasts resulted in reduced phosphorylation and activation of RAC1/Cdc42. In vitro kinase assays confirmed that recombinant Lrrk1 phosphorylated RAC1-GST protein, and immunoprecipitation showed that the interaction of Lrrk1 with RAC1 occurred within 10 min after RANKL treatment. Overexpression of constitutively active Q61L RAC1 partially rescued the resorptive function of Lrrk1-deficient osteoclasts. Furthermore, lack of Lrrk1 in osteoclasts led to reduced autophosphorylation of p21 protein-activated kinase-1 at Ser 144 , catalyzed by RAC1/Cdc42 binding and activation. Our data indicate that Lrrk1 regulates osteoclast function by directly modulating phosphorylation and activation of small GTPase RAC1/Cdc42 and that its function depends on ANK, ROC, WD40, and kinase domains. Copyright © 2016 the American Physiological Society.

  10. Rsr1 Focuses Cdc42 Activity at Hyphal Tips and Promotes Maintenance of Hyphal Development in Candida albicans

    Science.gov (United States)

    Pulver, Rebecca; Heisel, Timothy; Gonia, Sara; Robins, Robert; Norton, Jennifer; Haynes, Paula

    2013-01-01

    The extremely elongated morphology of fungal hyphae is dependent on the cell's ability to assemble and maintain polarized growth machinery over multiple cell cycles. The different morphologies of the fungus Candida albicans make it an excellent model organism in which to study the spatiotemporal requirements for constitutive polarized growth and the generation of different cell shapes. In C. albicans, deletion of the landmark protein Rsr1 causes defects in morphogenesis that are not predicted from study of the orthologous protein in the related yeast Saccharomyces cerevisiae, thus suggesting that Rsr1 has expanded functions during polarized growth in C. albicans. Here, we show that Rsr1 activity localizes to hyphal tips by the differential localization of the Rsr1 GTPase-activating protein (GAP), Bud2, and guanine nucleotide exchange factor (GEF), Bud5. In addition, we find that Rsr1 is needed to maintain the focused localization of hyphal polarity structures and proteins, including Bem1, a marker of the active GTP-bound form of the Rho GTPase, Cdc42. Further, our results indicate that tip-localized Cdc42 clusters are associated with the cell's ability to express a hyphal transcriptional program and that the ability to generate a focused Cdc42 cluster in early hyphae (germ tubes) is needed to maintain hyphal morphogenesis over time. We propose that in C. albicans, Rsr1 “fine-tunes” the distribution of Cdc42 activity and that self-organizing (Rsr1-independent) mechanisms of polarized growth are not sufficient to generate narrow cell shapes or to provide feedback to the transcriptional program during hyphal morphogenesis. PMID:23223038

  11. Defective homing is associated with altered Cdc42 activity in cells from patients with Fanconi anemia group A

    Science.gov (United States)

    Zhang, Xiaoling; Shang, Xun; Guo, Fukun; Murphy, Kim; Kirby, Michelle; Kelly, Patrick; Reeves, Lilith; Smith, Franklin O.; Williams, David A.

    2008-01-01

    Previous studies showed that Fanconi anemia (FA) murine stem cells have defective reconstitution after bone marrow (BM) transplantation. The mechanism underlying this defect is not known. Here, we report defective homing of FA patient BM progenitors transplanted into mouse models. Using cells from patients carrying mutations in FA complementation group A (FA-A), we show that when transplanted into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) recipient mice, FA-A BM cells exhibited impaired homing activity. FA-A cells also showed defects in both cell-cell and cell-matrix adhesion. Complementation of FA-A deficiency by reexpression of FANCA readily restored adhesion of FA-A cells. A significant decrease in the activity of the Rho GTPase Cdc42 was found associated with these defective functions in patient-derived cells, and expression of a constitutively active Cdc42 mutant was able to rescue the adhesion defect of FA-A cells. These results provide the first evidence that FA proteins influence human BM progenitor homing and adhesion via the small GTPase Cdc42-regulated signaling pathway. PMID:18565850

  12. The signaling pathway of Campylobacter jejuni-induced Cdc42 activation: Role of fibronectin, integrin beta1, tyrosine kinases and guanine exchange factor Vav2

    LENUS (Irish Health Repository)

    Krause-Gruszczynska, Malgorzata

    2011-12-28

    Abstract Background Host cell invasion by the foodborne pathogen Campylobacter jejuni is considered as one of the primary reasons of gut tissue damage, however, mechanisms and key factors involved in this process are widely unclear. It was reported that small Rho GTPases, including Cdc42, are activated and play a role during invasion, but the involved signaling cascades remained unknown. Here we utilised knockout cell lines derived from fibronectin-\\/-, integrin-beta1-\\/-, focal adhesion kinase (FAK)-\\/- and Src\\/Yes\\/Fyn-\\/- deficient mice, and wild-type control cells, to investigate C. jejuni-induced mechanisms leading to Cdc42 activation and bacterial uptake. Results Using high-resolution scanning electron microscopy, GTPase pulldowns, G-Lisa and gentamicin protection assays we found that each studied host factor is necessary for induction of Cdc42-GTP and efficient invasion. Interestingly, filopodia formation and associated membrane dynamics linked to invasion were only seen during infection of wild-type but not in knockout cells. Infection of cells stably expressing integrin-beta1 variants with well-known defects in fibronectin fibril formation or FAK signaling also exhibited severe deficiencies in Cdc42 activation and bacterial invasion. We further demonstrated that infection of wild-type cells induces increasing amounts of phosphorylated FAK and growth factor receptors (EGFR and PDGFR) during the course of infection, correlating with accumulating Cdc42-GTP levels and C. jejuni invasion over time. In studies using pharmacological inhibitors, silencing RNA (siRNA) and dominant-negative expression constructs, EGFR, PDGFR and PI3-kinase appeared to represent other crucial components upstream of Cdc42 and invasion. siRNA and the use of Vav1\\/2-\\/- knockout cells further showed that the guanine exchange factor Vav2 is required for Cdc42 activation and maximal bacterial invasion. Overexpression of certain mutant constructs indicated that Vav2 is a linker

  13. The signaling pathway of Campylobacter jejuni-induced Cdc42 activation: Role of fibronectin, integrin beta1, tyrosine kinases and guanine exchange factor Vav2

    Directory of Open Access Journals (Sweden)

    Krause-Gruszczynska Malgorzata

    2011-12-01

    Full Text Available Abstract Background Host cell invasion by the foodborne pathogen Campylobacter jejuni is considered as one of the primary reasons of gut tissue damage, however, mechanisms and key factors involved in this process are widely unclear. It was reported that small Rho GTPases, including Cdc42, are activated and play a role during invasion, but the involved signaling cascades remained unknown. Here we utilised knockout cell lines derived from fibronectin-/-, integrin-beta1-/-, focal adhesion kinase (FAK-/- and Src/Yes/Fyn-/- deficient mice, and wild-type control cells, to investigate C. jejuni-induced mechanisms leading to Cdc42 activation and bacterial uptake. Results Using high-resolution scanning electron microscopy, GTPase pulldowns, G-Lisa and gentamicin protection assays we found that each studied host factor is necessary for induction of Cdc42-GTP and efficient invasion. Interestingly, filopodia formation and associated membrane dynamics linked to invasion were only seen during infection of wild-type but not in knockout cells. Infection of cells stably expressing integrin-beta1 variants with well-known defects in fibronectin fibril formation or FAK signaling also exhibited severe deficiencies in Cdc42 activation and bacterial invasion. We further demonstrated that infection of wild-type cells induces increasing amounts of phosphorylated FAK and growth factor receptors (EGFR and PDGFR during the course of infection, correlating with accumulating Cdc42-GTP levels and C. jejuni invasion over time. In studies using pharmacological inhibitors, silencing RNA (siRNA and dominant-negative expression constructs, EGFR, PDGFR and PI3-kinase appeared to represent other crucial components upstream of Cdc42 and invasion. siRNA and the use of Vav1/2-/- knockout cells further showed that the guanine exchange factor Vav2 is required for Cdc42 activation and maximal bacterial invasion. Overexpression of certain mutant constructs indicated that Vav2 is a linker

  14. Frequent alterations of SLIT2–ROBO1–CDC42 signalling pathway ...

    Indian Academy of Sciences (India)

    breast cancer; alterations of SLIT2–ROBO1 signalling; active CDC42; ... proportion of four subtypes were tested for molecular alterations of SLIT2, ... reduced expression of phospho Serine-71 CDC42 predicted poor survival of BC patients.

  15. Gene targeting implicates Cdc42 GTPase in GPVI and non-GPVI mediated platelet filopodia formation, secretion and aggregation.

    Directory of Open Access Journals (Sweden)

    Huzoor Akbar

    Full Text Available Cdc42 and Rac1, members of the Rho family of small GTPases, play critical roles in actin cytoskeleton regulation. We have shown previously that Rac1 is involved in regulation of platelet secretion and aggregation. However, the role of Cdc42 in platelet activation remains controversial. This study was undertaken to better understand the role of Cdc42 in platelet activation.We utilized the Mx-cre;Cdc42(lox/lox inducible mice with transient Cdc42 deletion to investigate the involvement of Cdc42 in platelet function. The Cdc42-deficient mice exhibited a significantly reduced platelet count than the matching Cdc42(+/+ mice. Platelets isolated from Cdc42(-/-, as compared to Cdc42(+/+, mice exhibited (a diminished phosphorylation of PAK1/2, an effector molecule of Cdc42, (b inhibition of filopodia formation on immobilized CRP or fibrinogen, (c inhibition of CRP- or thrombin-induced secretion of ATP and release of P-selectin, (d inhibition of CRP, collagen or thrombin induced platelet aggregation, and (e minimal phosphorylation of Akt upon stimulation with CRP or thrombin. The bleeding times were significantly prolonged in Cdc42(-/- mice compared with Cdc42(+/+ mice.Our data demonstrate that Cdc42 is required for platelet filopodia formation, secretion and aggregation and therefore plays a critical role in platelet mediated hemostasis and thrombosis.

  16. Binding of Cdc42 to phospholipase D1 is important in neurite outgrowth of neural stem cells

    International Nuclear Information System (INIS)

    Yoon, Mee-Sup; Cho, Chan Ho; Lee, Ki Sung; Han, Joong-Soo

    2006-01-01

    We previously demonstrated that phospholipase D (PLD) expression and PLD activity are upregulated during neuronal differentiation. In the present study, employing neural stem cells from the brain cortex of E14 rat embryos, we investigated the role of Rho family GTPases in PLD activation and in neurite outgrowth of neural stem cells during differentiation. As neuronal differentiation progressed, the expression levels of Cdc42 and RhoA increased. Furthermore, Cdc42 and PLD1 were mainly localized in neurite, whereas RhoA was localized in cytosol. Co-immunoprecipitation revealed that Cdc42 was bound to PLD1 during differentiation, whereas RhoA was associated with PLD1 during both proliferation and differentiation. These results indicate that the association between Cdc42 and PLD1 is related to neuronal differentiation. To examine the effect of Cdc42 on PLD activation and neurite outgrowth, we transfected dominant negative Cdc42 (Cdc42N17) and constitutively active Cdc42 (Cdc42V12) into neural stem cells, respectively. Overexpression of Cdc42N17 decreased both PLD activity and neurite outgrowth, whereas co-transfection with Cdc42N17 and PLD1 restored them. On the other hand, Cdc42V12 increased both PLD activity and neurite outgrowth, suggesting that active state of Cdc42 is important in upregulation of PLD activity which is responsible for the increase of neurite outgrowth

  17. Hepatocyte-specific deletion of Cdc42 results in delayed liver regeneration after partial hepatectomy in mice

    DEFF Research Database (Denmark)

    Yuan, Haixin; Zhang, Hong; Wu, Xunwei

    2009-01-01

    Cdc42, a member of the Rho guanosine triphosphatase (GTPase) family, plays important roles in the regulation of the cytoskeleton, cell proliferation, cell polarity, and cellular transport, but little is known about its specific function in mammalian liver. We investigated the function of Cdc42...... in regulating liver regeneration. Using a mouse model with liver-specific knockout of Cdc42 (Cdc42LK), we studied liver regeneration after partial hepatectomy. Histological analysis, immunostaining, and western blot analysis were performed to characterize Cdc42LK livers and to explore the role of Cdc42 in liver...... regeneration. In control mouse livers, Cdc42 became activated between 3 and 24 hours after partial hepatectomy. Loss of Cdc42 led to a significant delay of liver recovery after partial hepatectomy, which was associated with reduced and delayed DNA synthesis indicated by 5-bromo-2'-deoxyuridine staining...

  18. Cdc42 regulates cofilin during the establishment of neuronal polarity

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  19. Interaction of the Small GTPase Cdc42 with Arginine Kinase Restricts White Spot Syndrome Virus in Shrimp.

    Science.gov (United States)

    Xu, Ji-Dong; Jiang, Hai-Shan; Wei, Tian-Di; Zhang, Ke-Yi; Wang, Xian-Wei; Zhao, Xiao-Fan; Wang, Jin-Xing

    2017-03-01

    Many types of small GTPases are widely expressed in eukaryotes and have different functions. As a crucial member of the Rho GTPase family, Cdc42 serves a number of functions, such as regulating cell growth, migration, and cell movement. Several RNA viruses employ Cdc42-hijacking tactics in their target cell entry processes. However, the function of Cdc42 in shrimp antiviral immunity is not clear. In this study, we identified a Cdc42 protein in the kuruma shrimp ( Marsupenaeus japonicus ) and named it Mj Cdc42. Mj Cdc42 was upregulated in shrimp challenged by white spot syndrome virus (WSSV). The knockdown of Mj Cdc42 and injection of Cdc42 inhibitors increased the proliferation of WSSV. Further experiments determined that Mj Cdc42 interacted with an arginine kinase ( Mj AK). By analyzing the binding activity and enzyme activity of Mj AK and its mutant, Δ Mj AK, we found that Mj AK could enhance the replication of WSSV in shrimp. Mj AK interacted with the envelope protein VP26 of WSSV. An inhibitor of AK activity, quercetin, could impair the function of Mj AK in WSSV replication. Further study demonstrated that the binding of Mj Cdc42 and Mj AK depends on Cys 271 of Mj AK and suppresses the WSSV replication-promoting effect of Mj AK. By interacting with the active site of Mj AK and suppressing its enzyme activity, Mj Cdc42 inhibits WSSV replication in shrimp. Our results demonstrate a new function of Cdc42 in the cellular defense against viral infection in addition to the regulation of actin and phagocytosis, which has been reported in previous studies. IMPORTANCE The interaction of Cdc42 with arginine kinase plays a crucial role in the host defense against WSSV infection. This study identifies a new mechanism of Cdc42 in innate immunity and enriches the knowledge of the antiviral innate immunity of invertebrates. Copyright © 2017 American Society for Microbiology.

  20. Cooperation of Rho family proteins Rac1 and Cdc42 in cartilage development and calcified tissue formation.

    Science.gov (United States)

    Ikehata, Mikiko; Yamada, Atsushi; Fujita, Koji; Yoshida, Yuko; Kato, Tadashi; Sakashita, Akiko; Ogata, Hiroaki; Iijima, Takehiko; Kuroda, Masahiko; Chikazu, Daichi; Kamijo, Ryutaro

    2018-04-20

    Rac1 and Cdc42, Rho family low molecular weight G proteins, are intracellular signaling factors that transmit various information from outside to inside cells. Primarily, they are known to control various biological activities mediated by actin cytoskeleton reorganization, such as cell proliferation, differentiation, and apoptosis. In order to investigate the functions of Rac1 and Cdc42 in bone formation, we prepared cartilage-specific double conditional knockout mice, Rac1 fl/fl ; Cdc42 fl/fl ; Col2-Cre (Rac1: Cdc42 dcKO mice), which died just after birth, similar to Cdc42 fl/fl ; Col2-Cre mice (Cdc42 cKO mice). Our findings showed that the long tubule bone in Rac1: Cdc42 dcKO mice was shorter than that in Rac1 fl/fl ; Col2-Cre mice (Rac1 cKO mice) and Cdc42 cKO mice. Abnormal skeleton formation was also observed and disordered columnar formation in the growth plate of the Rac1: Cdc42 dcKO mice was more severe as compared to the Rac1 cKO and Cdc42 cKO mice. Together, these results suggest that Rac1 and Cdc42 have cooperating roles in regulation of bone development. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Frequent alterations of SLIT2–ROBO1–CDC42 signalling pathway ...

    Indian Academy of Sciences (India)

    2016-09-07

    Sep 7, 2016 ... Keywords. breast cancer; alterations of SLIT2–ROBO1 signalling; active CDC42; pSer71-CDC42 . Journal of ... have already been studied in head and neck squamous cell ...... lung, oral, cervical, breast, kidney (Dallol et al.

  2. Functional Dysregulation of CDC42 Causes Diverse Developmental Phenotypes.

    Science.gov (United States)

    Martinelli, Simone; Krumbach, Oliver H F; Pantaleoni, Francesca; Coppola, Simona; Amin, Ehsan; Pannone, Luca; Nouri, Kazem; Farina, Luciapia; Dvorsky, Radovan; Lepri, Francesca; Buchholzer, Marcel; Konopatzki, Raphael; Walsh, Laurence; Payne, Katelyn; Pierpont, Mary Ella; Vergano, Samantha Schrier; Langley, Katherine G; Larsen, Douglas; Farwell, Kelly D; Tang, Sha; Mroske, Cameron; Gallotta, Ivan; Di Schiavi, Elia; Della Monica, Matteo; Lugli, Licia; Rossi, Cesare; Seri, Marco; Cocchi, Guido; Henderson, Lindsay; Baskin, Berivan; Alders, Mariëlle; Mendoza-Londono, Roberto; Dupuis, Lucie; Nickerson, Deborah A; Chong, Jessica X; Meeks, Naomi; Brown, Kathleen; Causey, Tahnee; Cho, Megan T; Demuth, Stephanie; Digilio, Maria Cristina; Gelb, Bruce D; Bamshad, Michael J; Zenker, Martin; Ahmadian, Mohammad Reza; Hennekam, Raoul C; Tartaglia, Marco; Mirzaa, Ghayda M

    2018-01-17

    Exome sequencing has markedly enhanced the discovery of genes implicated in Mendelian disorders, particularly for individuals in whom a known clinical entity could not be assigned. This has led to the recognition that phenotypic heterogeneity resulting from allelic mutations occurs more commonly than previously appreciated. Here, we report that missense variants in CDC42, a gene encoding a small GTPase functioning as an intracellular signaling node, underlie a clinically heterogeneous group of phenotypes characterized by variable growth dysregulation, facial dysmorphism, and neurodevelopmental, immunological, and hematological anomalies, including a phenotype resembling Noonan syndrome, a developmental disorder caused by dysregulated RAS signaling. In silico, in vitro, and in vivo analyses demonstrate that mutations variably perturb CDC42 function by altering the switch between the active and inactive states of the GTPase and/or affecting CDC42 interaction with effectors, and differentially disturb cellular and developmental processes. These findings reveal the remarkably variable impact that dominantly acting CDC42 mutations have on cell function and development, creating challenges in syndrome definition, and exemplify the importance of functional profiling for syndrome recognition and delineation. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  3. The small GTPase Cdc42 modulates the number of exocytosis-competent dense-core vesicles in PC12 cells

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Mai [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902 (Japan); Kitaguchi, Tetsuya [Cell Signaling Group, Waseda Bioscience Research Institute in Singapore (WABOIS), Waseda University, 11 Biopolis Way, 05-01/02 Helios, Singapore 138667 (Singapore); Numano, Rika [The Electronics-Inspired Interdisciplinary Research Institute (EIIRIS), Toyohashi University of Technology, 1-1 Hibarigaoka, Tennpaku-cho, Toyohashi, Aichi 441-8580 (Japan); Ikematsu, Kazuya [Forensic Pathology and Science, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523 (Japan); Kakeyama, Masaki [Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033 (Japan); Murata, Masayuki; Sato, Ken [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902 (Japan); Tsuboi, Takashi, E-mail: takatsuboi@bio.c.u-tokyo.ac.jp [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902 (Japan)

    2012-04-06

    Highlights: Black-Right-Pointing-Pointer Regulation of exocytosis by Rho GTPase Cdc42. Black-Right-Pointing-Pointer Cdc42 increases the number of fusion events from newly recruited vesicles. Black-Right-Pointing-Pointer Cdc42 increases the number of exocytosis-competent dense-core vesicles. -- Abstract: Although the small GTPase Rho family Cdc42 has been shown to facilitate exocytosis through increasing the amount of hormones released, the precise mechanisms regulating the quantity of hormones released on exocytosis are not well understood. Here we show by live cell imaging analysis under TIRF microscope and immunocytochemical analysis under confocal microscope that Cdc42 modulated the number of fusion events and the number of dense-core vesicles produced in the cells. Overexpression of a wild-type or constitutively-active form of Cdc42 strongly facilitated high-KCl-induced exocytosis from the newly recruited plasma membrane vesicles in PC12 cells. By contrast, a dominant-negative form of Cdc42 inhibited exocytosis from both the newly recruited and previously docked plasma membrane vesicles. The number of intracellular dense-core vesicles was increased by the overexpression of both a wild-type and constitutively-active form of Cdc42. Consistently, activation of Cdc42 by overexpression of Tuba, a Golgi-associated guanine nucleotide exchange factor for Cdc42 increased the number of intracellular dense-core vesicles, whereas inhibition of Cdc42 by overexpression of the Cdc42/Rac interactive binding domain of neuronal Wiskott-Aldrich syndrome protein decreased the number of them. These findings suggest that Cdc42 facilitates exocytosis by modulating both the number of exocytosis-competent dense-core vesicles and the production of dense-core vesicles in PC12 cells.

  4. The small GTPase Cdc42 modulates the number of exocytosis-competent dense-core vesicles in PC12 cells

    International Nuclear Information System (INIS)

    Sato, Mai; Kitaguchi, Tetsuya; Numano, Rika; Ikematsu, Kazuya; Kakeyama, Masaki; Murata, Masayuki; Sato, Ken; Tsuboi, Takashi

    2012-01-01

    Highlights: ► Regulation of exocytosis by Rho GTPase Cdc42. ► Cdc42 increases the number of fusion events from newly recruited vesicles. ► Cdc42 increases the number of exocytosis-competent dense-core vesicles. -- Abstract: Although the small GTPase Rho family Cdc42 has been shown to facilitate exocytosis through increasing the amount of hormones released, the precise mechanisms regulating the quantity of hormones released on exocytosis are not well understood. Here we show by live cell imaging analysis under TIRF microscope and immunocytochemical analysis under confocal microscope that Cdc42 modulated the number of fusion events and the number of dense-core vesicles produced in the cells. Overexpression of a wild-type or constitutively-active form of Cdc42 strongly facilitated high-KCl-induced exocytosis from the newly recruited plasma membrane vesicles in PC12 cells. By contrast, a dominant-negative form of Cdc42 inhibited exocytosis from both the newly recruited and previously docked plasma membrane vesicles. The number of intracellular dense-core vesicles was increased by the overexpression of both a wild-type and constitutively-active form of Cdc42. Consistently, activation of Cdc42 by overexpression of Tuba, a Golgi-associated guanine nucleotide exchange factor for Cdc42 increased the number of intracellular dense-core vesicles, whereas inhibition of Cdc42 by overexpression of the Cdc42/Rac interactive binding domain of neuronal Wiskott–Aldrich syndrome protein decreased the number of them. These findings suggest that Cdc42 facilitates exocytosis by modulating both the number of exocytosis-competent dense-core vesicles and the production of dense-core vesicles in PC12 cells.

  5. Cdc42-mediated tubulogenesis controls cell specification

    DEFF Research Database (Denmark)

    Kesavan, Gokul; Sand, Fredrik Wolfhagen; Greiner, Thomas Uwe

    2009-01-01

    Understanding how cells polarize and coordinate tubulogenesis during organ formation is a central question in biology. Tubulogenesis often coincides with cell-lineage specification during organ development. Hence, an elementary question is whether these two processes are independently controlled......, or whether proper cell specification depends on formation of tubes. To address these fundamental questions, we have studied the functional role of Cdc42 in pancreatic tubulogenesis. We present evidence that Cdc42 is essential for tube formation, specifically for initiating microlumen formation and later...... for maintaining apical cell polarity. Finally, we show that Cdc42 controls cell specification non-cell-autonomously by providing the correct microenvironment for proper control of cell-fate choices of multipotent progenitors. For a video summary of this article, see the PaperFlick file with the Supplemental Data...

  6. Cdc42 is crucial for the maturation of primordial cell junctions in keratinocytes independent of Rac1

    DEFF Research Database (Denmark)

    Du, Dan; Pedersen, Esben; Wang, Zhipeng

    2008-01-01

    Cell-cell contacts are crucial for the integrity of all tissues. Contrasting reports have been published about the role of Cdc42 in epithelial cell-cell contacts in vitro. In keratinocytes, it was suggested that Rac1 and not Cdc42 is crucial for the formation of mature epithelial junctions, based...... on dominant negative inhibition experiments. Deletion of the Cdc42 gene in keratinocytes in vivo slowly impaired the maintenance of cell-cell contacts by an increased degradation of beta-catenin. Whether Cdc42 is required for the formation of mature junctions was not tested. We show now that Cdc42-deficient...... immortalized and primary keratinocytes form only punctate primordial cell contacts in vitro, which cannot mature into belt-like junctions. This defect was independent of enhanced degradation of beta-catenin, but correlated to an impaired activation and localization of aPKCzeta in the Cdc42-null keratinocytes...

  7. A crucial role for CDC42 in senescence-associated inflammation and atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Takashi K Ito

    Full Text Available Risk factors for atherosclerosis accelerate the senescence of vascular endothelial cells and promote atherogenesis by inducing vascular inflammation. A hallmark of endothelial senescence is the persistent up-regulation of pro-inflammatory genes. We identified CDC42 signaling as a mediator of chronic inflammation associated with endothelial senescence. Inhibition of CDC42 or NF-κB signaling attenuated the sustained up-regulation of pro-inflammatory genes in senescent human endothelial cells. Endothelium-specific activation of the p53/p21 pathway, a key mediator of senescence, also resulted in up-regulation of pro-inflammatory molecules in mice, which was reversed by Cdc42 deletion in endothelial cells. Likewise, endothelial-specific deletion of Cdc42 significantly attenuated chronic inflammation and plaque formation in atherosclerotic mice. While inhibition of NF-κB suppressed the pro-inflammatory responses in acute inflammation, the influence of Cdc42 deletion was less marked. Knockdown of cdc-42 significantly down-regulated pro-inflammatory gene expression and restored the shortened lifespan to normal in mutant worms with enhanced inflammation. These findings indicate that the CDC42 pathway is critically involved in senescence-associated inflammation and could be a therapeutic target for chronic inflammation in patients with age-related diseases without compromising host defenses.

  8. Essential roles of Cdc42 and MAPK in cadmium-induced apoptosis in Litopenaeus vannamei

    International Nuclear Information System (INIS)

    Peng, Ting; Wang, Wei-Na; Gu, Mei-Mei; Xie, Chen-Ying; Xiao, Yu-Chao; Liu, Yuan; Wang, Lei

    2015-01-01

    Highlights: • Cd 2+ induces Cdc42 and MAPKs pathway related gene of Litopenaeus vannamei up-regulation. • Reduction of THC, increase of ROS production and apoptotic cell rate were observed when the shrimps exposure to Cd 2+ . • DsRNA-suppression of LvCdc42 and MAPKs during Cd 2+ stress reduces the ROS production and apoptosis. • We conclude that LvCdc42 and MAPKs play key roles in Cd 2+ stress responses of shrimps. - Abstract: Cadmium, one of the most toxic heavy metals in aquatic environments, has severe effects on marine invertebrates and fishes. The MAPK signaling pathway plays a vital role in stress responses of animals. The mitogen-activated protein kinase (MAPK) signaling pathway plays a vital role in animals’ stress responses, including mediation of apoptosis induced by the Rho GTPase Cdc42. However, there is limited knowledge about its function in shrimps, although disorders exacerbated by environmental stresses (including heavy metal pollution) have caused serious mortality in commercially cultured shrimps. Thus, we probed roles of Cdc42 in Litopenaeus vannamei shrimps (LvCdc42) during cadmium exposure by inhibiting its expression using dsRNA-mediated RNA interference. The treatment successfully reduced expression levels of MAPKs (including p38, JNK, and ERK). Cadmium exposure induced significant increases in expression levels of LvCdc42 and MAPKs, accompanied by reductions in total hemocyte counts (THC) and increases in apoptotic hemocyte ratios and ROS production. However, all of these responses were much weaker in LvCdc42-suppressed shrimps, in which mortality rates were higher than in controls. Our results suggest that the MAPK pathway plays a vital role in shrimps’ responses to Cd 2+ . They also indicate that LvCdc42 in shrimps participates in its regulation, and thus plays key roles in ROS production, regulation of apoptosis and associated stress responses

  9. Essential roles of Cdc42 and MAPK in cadmium-induced apoptosis in Litopenaeus vannamei

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Ting; Wang, Wei-Na, E-mail: weina63@aliyun.com; Gu, Mei-Mei; Xie, Chen-Ying; Xiao, Yu-Chao; Liu, Yuan; Wang, Lei

    2015-06-15

    Highlights: • Cd{sup 2+} induces Cdc42 and MAPKs pathway related gene of Litopenaeus vannamei up-regulation. • Reduction of THC, increase of ROS production and apoptotic cell rate were observed when the shrimps exposure to Cd{sup 2+}. • DsRNA-suppression of LvCdc42 and MAPKs during Cd{sup 2+} stress reduces the ROS production and apoptosis. • We conclude that LvCdc42 and MAPKs play key roles in Cd{sup 2+} stress responses of shrimps. - Abstract: Cadmium, one of the most toxic heavy metals in aquatic environments, has severe effects on marine invertebrates and fishes. The MAPK signaling pathway plays a vital role in stress responses of animals. The mitogen-activated protein kinase (MAPK) signaling pathway plays a vital role in animals’ stress responses, including mediation of apoptosis induced by the Rho GTPase Cdc42. However, there is limited knowledge about its function in shrimps, although disorders exacerbated by environmental stresses (including heavy metal pollution) have caused serious mortality in commercially cultured shrimps. Thus, we probed roles of Cdc42 in Litopenaeus vannamei shrimps (LvCdc42) during cadmium exposure by inhibiting its expression using dsRNA-mediated RNA interference. The treatment successfully reduced expression levels of MAPKs (including p38, JNK, and ERK). Cadmium exposure induced significant increases in expression levels of LvCdc42 and MAPKs, accompanied by reductions in total hemocyte counts (THC) and increases in apoptotic hemocyte ratios and ROS production. However, all of these responses were much weaker in LvCdc42-suppressed shrimps, in which mortality rates were higher than in controls. Our results suggest that the MAPK pathway plays a vital role in shrimps’ responses to Cd{sup 2+}. They also indicate that LvCdc42 in shrimps participates in its regulation, and thus plays key roles in ROS production, regulation of apoptosis and associated stress responses.

  10. Coordination by Cdc42 of Actin, Contractility, and Adhesion for Melanoblast Movement in Mouse Skin

    DEFF Research Database (Denmark)

    Woodham, Emma F; Paul, Nikki R; Tyrrell, Benjamin

    2017-01-01

    traverse the dermis to reach the epidermis of the skin and hair follicles. We previously established that Rac1 signals via Scar/WAVE and Arp2/3 to effect pseudopod extension and migration of melanoblasts in skin. Here we show that RhoA is redundant in the melanocyte lineage but that Cdc42 coordinates...... multiple motility systems independent of Rac1. Similar to Rac1 knockouts, Cdc42 null mice displayed a severe loss of pigmentation, and melanoblasts showed cell-cycle progression, migration, and cytokinesis defects. However, unlike Rac1 knockouts, Cdc42 null melanoblasts were elongated and displayed large...... null cells lacked the ability to polarize their Golgi and coordinate motility systems for efficient movement. Loss of Cdc42 de-coupled three main systems: actin assembly via the formin FMNL2 and Arp2/3, active myosin-II localization, and integrin-based adhesion dynamics....

  11. Cdc42 and RhoA reveal different spatio-temporal dynamics upon local stimulation with Semaphorin-3A

    Directory of Open Access Journals (Sweden)

    Federico eIseppon

    2015-08-01

    Full Text Available Small RhoGTPases, such as Cdc42 and RhoA, are key players in integrating external cues and intracellular signaling pathways that regulate growth cone (GC motility. Indeed, Cdc42 is involved in actin polymerization and filopodia formation, whereas RhoA induces GC collapse and neurite retraction through actomyosin contraction. In this study we employed Förster Resonance Energy Transfer (FRET microscopy to study the spatio-temporal dynamics of Cdc42 and RhoA in GCs in response to local Semaphorin-3A stimulation obtained with lipid vesicles filled with Semaphorin-3A and positioned near the selected GC using optical tweezers. We found that Cdc42 and RhoA were activated at the leading edge of NG108-15 neuroblastoma cells during spontaneous cycles of protrusion and retraction, respectively. The release of Semaphorin-3A brought to a progressive activation of RhoA within 30 seconds from the stimulus in the central region of the GC that collapsed and retracted. In contrast, the same stimulation evoked waves of Cdc42 activation propagating away from the stimulated region. A more localized stimulation obtained with Sema3A coated beads placed on the GC, led to Cdc42 active waves that propagated in a retrograde manner with a mean period of 70 seconds, and followed by GC retraction. Therefore, Semaphorin-3A activates both Cdc42 and RhoA with a complex and different spatial-temporal dynamics.

  12. Cdc42 promotes host defenses against fatal infection

    DEFF Research Database (Denmark)

    Lee, Keunwook; Boyd, Kelli L; Parekh, Diptiben V

    2013-01-01

    attempted to specifically delete it in these cells by crossing the Cdc42(fl/fl) mouse with a FSP-1 cre mouse, which is thought to mediate recombination exclusively in fibroblasts. Surprisingly, the FSP-1cre;Cdc42(fl/fl) mice died at 3 weeks of age due to overwhelming suppurative upper airway infections...... showed that in addition to fibroblasts, the FSP-1 cre deleted Cdc42 very efficiently in all leukocytes. Thus, by using this non-specific cre mouse we inadvertently demonstrated the importance of Cdc42 in host protection from lethal infections and suggest a critical role for this small GTPase in innate...

  13. Rac1 and Cdc42 are regulators of HRasV12-transformation and angiogenic factors in human fibroblasts

    Directory of Open Access Journals (Sweden)

    Dao Kim-Hien T

    2010-01-01

    Full Text Available Abstract Background The activities of Rac1 and Cdc42 are essential for HRas-induced transformation of rodent fibroblasts. What is more, expression of constitutively activated mutants of Rac1 and/or Cdc42 is sufficient for their malignant transformation. The role for these two Rho GTPases in HRas-mediated transformation of human fibroblasts has not been studied. Here we evaluated the contribution of Rac1 and Cdc42 to maintaining HRas-induced transformation of human fibroblasts, and determined the ability of constitutively activated mutants of Rac1 or Cdc42 to induce malignant transformation of a human fibroblast cell strain. Methods Under the control of a tetracycline regulatable promoter, dominant negative mutants of Rac1 and Cdc42 were expressed in a human HRas-transformed, tumor derived fibroblast cell line. These cells were used to determine the roles of Rac1 and/or Cdc42 proteins in maintaining HRas-induced transformed phenotypes. Similarly, constitutively active mutants were expressed in a non-transformed human fibroblast cell strain to evaluate their potential to induce malignant transformation. Affymetrix GeneChip arrays were used for transcriptome analyses, and observed expression differences were subsequently validated using protein assays. Results Expression of dominant negative Rac1 and/or Cdc42 significantly altered transformed phenotypes of HRas malignantly transformed human fibroblasts. In contrast, expression of constitutively active mutants of Rac1 or Cdc42 was not sufficient to induce malignant transformation. Microarray analysis revealed that the expression of 29 genes was dependent on Rac1 and Cdc42, many of which are known to play a role in cancer. The dependence of two such genes, uPA and VEGF was further validated in both normoxic and hypoxic conditions. Conclusion(s The results presented here indicate that expression of both Rac1 and Cdc42 is necessary for maintaining several transformed phenotypes in oncogenic HRas

  14. Rac1 and Cdc42 are regulators of HRasV12-transformation and angiogenic factors in human fibroblasts

    International Nuclear Information System (INIS)

    Appledorn, Daniel M; Dao, Kim-Hien T; O'Reilly, Sandra; Maher, Veronica M; McCormick, J Justin

    2010-01-01

    The activities of Rac1 and Cdc42 are essential for HRas-induced transformation of rodent fibroblasts. What is more, expression of constitutively activated mutants of Rac1 and/or Cdc42 is sufficient for their malignant transformation. The role for these two Rho GTPases in HRas-mediated transformation of human fibroblasts has not been studied. Here we evaluated the contribution of Rac1 and Cdc42 to maintaining HRas-induced transformation of human fibroblasts, and determined the ability of constitutively activated mutants of Rac1 or Cdc42 to induce malignant transformation of a human fibroblast cell strain. Under the control of a tetracycline regulatable promoter, dominant negative mutants of Rac1 and Cdc42 were expressed in a human HRas-transformed, tumor derived fibroblast cell line. These cells were used to determine the roles of Rac1 and/or Cdc42 proteins in maintaining HRas-induced transformed phenotypes. Similarly, constitutively active mutants were expressed in a non-transformed human fibroblast cell strain to evaluate their potential to induce malignant transformation. Affymetrix GeneChip arrays were used for transcriptome analyses, and observed expression differences were subsequently validated using protein assays. Expression of dominant negative Rac1 and/or Cdc42 significantly altered transformed phenotypes of HRas malignantly transformed human fibroblasts. In contrast, expression of constitutively active mutants of Rac1 or Cdc42 was not sufficient to induce malignant transformation. Microarray analysis revealed that the expression of 29 genes was dependent on Rac1 and Cdc42, many of which are known to play a role in cancer. The dependence of two such genes, uPA and VEGF was further validated in both normoxic and hypoxic conditions. The results presented here indicate that expression of both Rac1 and Cdc42 is necessary for maintaining several transformed phenotypes in oncogenic HRas transformed human cells, including their ability to form tumors in athymic

  15. Cdc42 controls primary mesenchyme cell morphogenesis in the sea urchin embryo.

    Science.gov (United States)

    Sepúlveda-Ramírez, Silvia P; Toledo-Jacobo, Leslie; Henson, John H; Shuster, Charles B

    2018-05-15

    In the sea urchin embryo, gastrulation is characterized by the ingression and directed cell migration of primary mesenchyme cells (PMCs), as well as the primary invagination and convergent extension of the endomesoderm. Like all cell shape changes, individual and collective cell motility is orchestrated by Rho family GTPases and their modulation of the actomyosin cytoskeleton. And while endomesoderm specification has been intensively studied in echinoids, much less is known about the proximate regulators driving cell motility. Toward these ends, we employed anti-sense morpholinos, mutant alleles and pharmacological inhibitors to assess the role of Cdc42 during sea urchin gastrulation. While inhibition of Cdc42 expression or activity had only mild effects on PMC ingression, PMC migration, alignment and skeletogenesis were disrupted in the absence of Cdc42, as well as elongation of the archenteron. PMC migration and patterning of the larval skeleton relies on the extension of filopodia, and Cdc42 was required for filopodia in vivo as well as in cultured PMCs. Lastly, filopodial extension required both Arp2/3 and formin actin-nucleating factors, supporting models of filopodial nucleation observed in other systems. Together, these results suggest that Cdc42 plays essential roles during PMC cell motility and organogenesis. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Unraveling the molecular mechanism of interactions of the Rho GTPases Cdc42 and Rac1 with the scaffolding protein IQGAP2.

    Science.gov (United States)

    Ozdemir, E Sila; Jang, Hyunbum; Gursoy, Attila; Keskin, Ozlem; Li, Zhigang; Sacks, David B; Nussinov, Ruth

    2018-03-09

    IQ motif-containing GTPase-activating proteins (IQGAPs) are scaffolding proteins playing central roles in cell-cell adhesion, polarity, and motility. The Rho GTPases Cdc42 and Rac1, in their GTP-bound active forms, interact with all three human IQGAPs. The IQGAP-Cdc42 interaction promotes metastasis by enhancing actin polymerization. However, despite their high sequence identity, Cdc42 and Rac1 differ in their interactions with IQGAP. Two Cdc42 molecules can bind to the Ex-domain and the RasGAP site of the GTPase-activating protein (GAP)-related domain (GRD) of IQGAP and promote IQGAP dimerization. Only one Rac1 molecule might bind to the RasGAP site of GRD and may not facilitate the dimerization, and the exact mechanism of Cdc42 and Rac1 binding to IQGAP is unclear. Using all-atom molecular dynamics simulations, site-directed mutagenesis, and Western blotting, we unraveled the detailed mechanisms of Cdc42 and Rac1 interactions with IQGAP2. We observed that Cdc42 binding to the Ex-domain of GRD of IQGAP2 (GRD2) releases the Ex-domain at the C-terminal region of GRD2, facilitating IQGAP2 dimerization. Cdc42 binding to the Ex-domain promoted allosteric changes in the RasGAP site, providing a binding site for the second Cdc42 in the RasGAP site. Of note, the Cdc42 "insert loop" was important for the interaction of the first Cdc42 with the Ex-domain. By contrast, differences in Rac1 insert-loop sequence and structure precluded its interaction with the Ex-domain. Rac1 could bind only to the RasGAP site of apo-GRD2 and could not facilitate IQGAP2 dimerization. Our detailed mechanistic insights help decipher how Cdc42 can stimulate actin polymerization in metastasis.

  17. A New Genetically Encoded Single-Chain Biosensor for Cdc42 Based on FRET, Useful for Live-Cell Imaging

    Science.gov (United States)

    Cox, Dianne; Hodgson, Louis

    2014-01-01

    Cdc42 is critical in a myriad of cellular morphogenic processes, requiring precisely regulated activation dynamics to affect specific cellular events. To facilitate direct observations of Cdc42 activation in live cells, we developed and validated a new biosensor of Cdc42 activation. The biosensor is genetically encoded, of single-chain design and capable of correctly localizing to membrane compartments as well as interacting with its upstream regulators including the guanine nucleotide dissociation inhibitor. We characterized this new biosensor in motile mouse embryonic fibroblasts and observed robust activation dynamics at leading edge protrusions, similar to those previously observed for endogenous Cdc42 using the organic dye-based biosensor system. We then extended our validations and observations of Cdc42 activity to macrophages, and show that this new biosensor is able to detect differential activation patterns during phagocytosis and cytokine stimulation. Furthermore, we observe for the first time, a highly transient and localized activation of Cdc42 during podosome formation in macrophages, which was previously hypothesized but never directly visualized. PMID:24798463

  18. Cdc42 and Tks5: a minimal and universal molecular signature for functional invadosomes.

    Science.gov (United States)

    Di Martino, Julie; Paysan, Lisa; Gest, Caroline; Lagrée, Valérie; Juin, Amélie; Saltel, Frédéric; Moreau, Violaine

    2014-01-01

    Invadosomes are actin-based structures involved in extracellular-matrix degradation. Invadosomes, either known as podosomes or invadopodia, are found in an increasing number of cell types. Moreover, their overall organization and molecular composition may vary from one cell type to the other. Some are constitutive such as podosomes in hematopoietic cells whereas others are inducible. However, they share the same feature, their ability to interact and to degrade the extracellular matrix. Based on the literature and our own experiments, the aim of this study was to establish a minimal molecular definition of active invadosomes. We first highlighted that Cdc42 is the key RhoGTPase involved in invadosome formation in all described models. Using different cellular models, such as NIH-3T3, HeLa, and endothelial cells, we demonstrated that overexpression of an active form of Cdc42 is sufficient to form invadosome actin cores. Therefore, active Cdc42 must be considered not only as an inducer of filopodia, but also as an inducer of invadosomes. Depending on the expression level of Tks5, these Cdc42-dependent actin cores were endowed or not with a proteolytic activity. In fact, Tks5 overexpression rescued this activity in Tks5 low expressing cells. We thus described the adaptor protein Tks5 as a major actor of the invadosome degradation function. Surprisingly, we found that Src kinases are not always required for invadosome formation and function. These data suggest that even if Src family members are the principal kinases involved in the majority of invadosomes, it cannot be considered as a common element for all invadosome structures. We thus define a minimal and universal molecular signature of invadosome that includes Cdc42 activity and Tks5 presence in order to drive the actin machinery and the proteolytic activity of these invasive structures.

  19. Cdc42/N-WASP signaling links actin dynamics to pancreatic β cell delamination and differentiation

    Science.gov (United States)

    Kesavan, Gokul; Lieven, Oliver; Mamidi, Anant; Öhlin, Zarah Löf; Johansson, Jenny Kristina; Li, Wan-Chun; Lommel, Silvia; Greiner, Thomas Uwe; Semb, Henrik

    2014-01-01

    Delamination plays a pivotal role during normal development and cancer. Previous work has demonstrated that delamination and epithelial cell movement within the plane of an epithelium are associated with a change in cellular phenotype. However, how this positional change is linked to differentiation remains unknown. Using the developing mouse pancreas as a model system, we show that β cell delamination and differentiation are two independent events, which are controlled by Cdc42/N-WASP signaling. Specifically, we show that expression of constitutively active Cdc42 in β cells inhibits β cell delamination and differentiation. These processes are normally associated with junctional actin and cell-cell junction disassembly and the expression of fate-determining transcription factors, such as Isl1 and MafA. Mechanistically, we demonstrate that genetic ablation of N-WASP in β cells expressing constitutively active Cdc42 partially restores both delamination and β cell differentiation. These findings elucidate how junctional actin dynamics via Cdc42/N-WASP signaling cell-autonomously control not only epithelial delamination but also cell differentiation during mammalian organogenesis. PMID:24449844

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

    Science.gov (United States)

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

    2018-05-01

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

  1. The structure of FMNL2-Cdc42 yields insights into the mechanism of lamellipodia and filopodia formation

    Science.gov (United States)

    Kühn, Sonja; Erdmann, Constanze; Kage, Frieda; Block, Jennifer; Schwenkmezger, Lisa; Steffen, Anika; Rottner, Klemens; Geyer, Matthias

    2015-05-01

    Formins are actin polymerization factors that elongate unbranched actin filaments at the barbed end. Rho family GTPases activate Diaphanous-related formins through the relief of an autoregulatory interaction. The crystal structures of the N-terminal domains of human FMNL1 and FMNL2 in complex with active Cdc42 show that Cdc42 mediates contacts with all five armadillo repeats of the formin with specific interactions formed by the Rho-GTPase insert helix. Mutation of three residues within Rac1 results in a gain-of-function mutation for FMNL2 binding and reconstitution of the Cdc42 phenotype in vivo. Dimerization of FMNL1 through a parallel coiled coil segment leads to formation of an umbrella-shaped structure that--together with Cdc42--spans more than 15 nm in diameter. The two interacting FMNL-Cdc42 heterodimers expose six membrane interaction motifs on a convex protein surface, the assembly of which may facilitate actin filament elongation at the leading edge of lamellipodia and filopodia.

  2. Prominin-2 expression increases protrusions, decreases caveolae and inhibits Cdc42 dependent fluid phase endocytosis

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Raman Deep, E-mail: Takhter.Ramandeep@mayo.edu; Schroeder, Andreas S.; Scheffer, Luana; Holicky, Eileen L.; Wheatley, Christine L.; Marks, David L., E-mail: Marks.david@mayo.edu; Pagano, Richard E.

    2013-05-10

    Highlights: •Prominin-2 expression induced protrusions that co-localized with lipid raft markers. •Prominin-2 expression decreased caveolae, caveolar endocytosis and increased pCav1. •Prominin-2 expression inhibited fluid phase endocytosis by inactivation of Cdc42. •These endocytic effects can be reversed by adding exogenous cholesterol. •Caveolin1 knockdown restored fluid phase endocytosis in Prominin2 expressing cells. -- Abstract: Background: Membrane protrusions play important roles in biological processes such as cell adhesion, wound healing, migration, and sensing of the external environment. Cell protrusions are a subtype of membrane microdomains composed of cholesterol and sphingolipids, and can be disrupted by cholesterol depletion. Prominins are pentaspan membrane proteins that bind cholesterol and localize to plasma membrane (PM) protrusions. Prominin-1 is of great interest as a marker for stem and cancer cells, while Prominin-2 (Prom2) is reportedly restricted to epithelial cells. Aim: To characterize the effects of Prom-2 expression on PM microdomain organization. Methods: Prom2-fluorescent protein was transfected in human skin fibroblasts (HSF) and Chinese hamster ovary (CHO) cells for PM raft and endocytic studies. Caveolae at PM were visualized using transmission electron microscopy. Cdc42 activation was measured and caveolin-1 knockdown was performed using siRNAs. Results: Prom2 expression in HSF and CHO cells caused extensive Prom2-positive protrusions that co-localized with lipid raft markers. Prom2 expression significantly decreased caveolae at the PM, reduced caveolar endocytosis and increased caveolin-1 phosphorylation. Prom2 expression also inhibited Cdc42-dependent fluid phase endocytosis via decreased Cdc42 activation. Effects on endocytosis were reversed by addition of cholesterol. Knockdown of caveolin-1 by siRNA restored Cdc42 dependent fluid phase endocytosis in Prom2-expressing cells. Conclusions: Prom2 protrusions primarily

  3. Rac1 and Cdc42 GTPases regulate shear stress-driven β-catenin signaling in osteoblasts

    International Nuclear Information System (INIS)

    Wan, Qiaoqiao; Cho, Eunhye; Yokota, Hiroki; Na, Sungsoo

    2013-01-01

    Highlights: •Shear stress increased TCF/LEF activity and stimulated β-catenin nuclear localization. •Rac1, Cdc42, and RhoA displayed distinct dynamic activity patterns under flow. •Rac1 and Cdc42, but not RhoA, regulate shear stress-driven TCF/LEF activation. •Cytoskeleton did not significantly affect shear stress-induced TCF/LEF activation. -- Abstract: Beta-catenin-dependent TCF/LEF (T-cell factor/lymphocyte enhancing factor) is known to be mechanosensitive and an important regulator for promoting bone formation. However, the functional connection between TCF/LEF activity and Rho family GTPases is not well understood in osteoblasts. Herein we investigated the molecular mechanisms underlying oscillatory shear stress-induced TCF/LEF activity in MC3T3-E1 osteoblast cells using live cell imaging. We employed fluorescence resonance energy transfer (FRET)-based and green fluorescent protein (GFP)-based biosensors, which allowed us to monitor signal transduction in living cells in real time. Oscillatory (1 Hz) shear stress (10 dynes/cm 2 ) increased TCF/LEF activity and stimulated translocation of β-catenin to the nucleus with the distinct activity patterns of Rac1 and Cdc42. The shear stress-induced TCF/LEF activity was blocked by the inhibition of Rac1 and Cdc42 with their dominant negative mutants or selective drugs, but not by a dominant negative mutant of RhoA. In contrast, constitutively active Rac1 and Cdc42 mutants caused a significant enhancement of TCF/LEF activity. Moreover, activation of Rac1 and Cdc42 increased the basal level of TCF/LEF activity, while their inhibition decreased the basal level. Interestingly, disruption of cytoskeletal structures or inhibition of myosin activity did not significantly affect shear stress-induced TCF/LEF activity. Although Rac1 is reported to be involved in β-catenin in cancer cells, the involvement of Cdc42 in β-catenin signaling in osteoblasts has not been identified. Our findings in this study demonstrate

  4. Rac1 and Cdc42 GTPases regulate shear stress-driven β-catenin signaling in osteoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Wan, Qiaoqiao; Cho, Eunhye [Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202 (United States); Yokota, Hiroki [Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202 (United States); Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202 (United States); Na, Sungsoo, E-mail: sungna@iupui.edu [Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202 (United States)

    2013-04-19

    Highlights: •Shear stress increased TCF/LEF activity and stimulated β-catenin nuclear localization. •Rac1, Cdc42, and RhoA displayed distinct dynamic activity patterns under flow. •Rac1 and Cdc42, but not RhoA, regulate shear stress-driven TCF/LEF activation. •Cytoskeleton did not significantly affect shear stress-induced TCF/LEF activation. -- Abstract: Beta-catenin-dependent TCF/LEF (T-cell factor/lymphocyte enhancing factor) is known to be mechanosensitive and an important regulator for promoting bone formation. However, the functional connection between TCF/LEF activity and Rho family GTPases is not well understood in osteoblasts. Herein we investigated the molecular mechanisms underlying oscillatory shear stress-induced TCF/LEF activity in MC3T3-E1 osteoblast cells using live cell imaging. We employed fluorescence resonance energy transfer (FRET)-based and green fluorescent protein (GFP)-based biosensors, which allowed us to monitor signal transduction in living cells in real time. Oscillatory (1 Hz) shear stress (10 dynes/cm{sup 2}) increased TCF/LEF activity and stimulated translocation of β-catenin to the nucleus with the distinct activity patterns of Rac1 and Cdc42. The shear stress-induced TCF/LEF activity was blocked by the inhibition of Rac1 and Cdc42 with their dominant negative mutants or selective drugs, but not by a dominant negative mutant of RhoA. In contrast, constitutively active Rac1 and Cdc42 mutants caused a significant enhancement of TCF/LEF activity. Moreover, activation of Rac1 and Cdc42 increased the basal level of TCF/LEF activity, while their inhibition decreased the basal level. Interestingly, disruption of cytoskeletal structures or inhibition of myosin activity did not significantly affect shear stress-induced TCF/LEF activity. Although Rac1 is reported to be involved in β-catenin in cancer cells, the involvement of Cdc42 in β-catenin signaling in osteoblasts has not been identified. Our findings in this study demonstrate

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

    Directory of Open Access Journals (Sweden)

    Uta Meyer Zum Büschenfelde

    2018-05-01

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

  6. Cdc42 regulates epithelial cell polarity and cytoskeletal function during kidney tubule development

    DEFF Research Database (Denmark)

    Elias, Bertha C; Das, Amrita; Parekh, Diptiben V

    2015-01-01

    The Rho GTPase Cdc42 regulates key signaling pathways required for multiple cell functions, including maintenance of shape, polarity, proliferation, migration, differentiation and morphogenesis. Although previous studies have shown that Cdc42 is required for proper epithelial development and main......The Rho GTPase Cdc42 regulates key signaling pathways required for multiple cell functions, including maintenance of shape, polarity, proliferation, migration, differentiation and morphogenesis. Although previous studies have shown that Cdc42 is required for proper epithelial development...

  7. Redundant and nonredundant roles for Cdc42 and Rac1 in lymphomas developed in NPM-ALK transgenic mice

    DEFF Research Database (Denmark)

    Choudhari, Ramesh; Minero, Valerio Giacomo; Menotti, Matteo

    2016-01-01

    Increasing evidence suggests that Rho family GTPases could have a critical role in the biology of T-cell lymphoma. In ALK-rearranged anaplastic large cell lymphoma (ALCL), a specific subtype of T-cell lymphoma, the Rho family GTPases Cdc42 and Rac1 are activated by the ALK oncogenic activity. In ...

  8. Estrogen and Resveratrol Regulate Rac and Cdc42 Signaling to the Actin Cytoskeleton of Metastatic Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Nicolas G. Azios

    2007-02-01

    Full Text Available Estrogen and structurally related molecules play critical roles in breast cancer. We reported that resveratrol (50 µM, an estrogen-like phytosterol from grapes, acts in an antiestrogenic manner in breast cancer cells to reduce cell migration and to induce a global and sustained extension of actin structures called filopodia. Herein, we report that resveratrol-induced filopodia formation is time-dependent and concentration-dependent. In contrast to resveratrol at 50 µM, resveratrol at 5 µM acts in a manner similar to estrogen by increasing lamellipodia, as well as cell migration and invasion. Because Rho GTPases regulate the extension of actin structures, we investigated a role for Rac and Cdc42 in estrogen and resveratrol signaling. Our results demonstrate that 50 µM resveratrol decreases Rac and Cdc42 activity, whereas estrogen and 5 µM resveratrol increase Rac activity in breast cancer cells. MDA-MB-231 cells expressing dominant-negative Cdc42 or dominantnegative Rac retain filopodia response to 50 µM resveratrol. Lamellipodia response to 5 µM resveratrol, estrogen, or epidermal growth factor is inhibited in cells expressing dominant-negative Rac, indicating that Rac regulates estrogen and resveratrol (5 µM signaling to the actin cytoskeleton. These results indicate that signaling to the actin cytoskeleton by low and high concentrations of resveratrol may be differentially regulated by Rac and Cdc42.

  9. Loss of Cdc42 leads to defects in synaptic plasticity and remote memory recall.

    Science.gov (United States)

    Kim, Il Hwan; Wang, Hong; Soderling, Scott H; Yasuda, Ryohei

    2014-07-08

    Cdc42 is a signaling protein important for reorganization of actin cytoskeleton and morphogenesis of cells. However, the functional role of Cdc42 in synaptic plasticity and in behaviors such as learning and memory are not well understood. Here we report that postnatal forebrain deletion of Cdc42 leads to deficits in synaptic plasticity and in remote memory recall using conditional knockout of Cdc42. We found that deletion of Cdc42 impaired LTP in the Schaffer collateral synapses and postsynaptic structural plasticity of dendritic spines in CA1 pyramidal neurons in the hippocampus. Additionally, loss of Cdc42 did not affect memory acquisition, but instead significantly impaired remote memory recall. Together these results indicate that the postnatal functions of Cdc42 may be crucial for the synaptic plasticity in hippocampal neurons, which contribute to the capacity for remote memory recall.

  10. miR-330 regulates the proliferation of colorectal cancer cells by targeting Cdc42

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuefeng [The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001 (China); Zhu, Xiaolan; Xu, Wenlin [The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001 (China); Wang, Dongqing [The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001 (China); Yan, Jinchuan, E-mail: jiangdalyf2009@126.com [The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001 (China)

    2013-02-15

    Highlights: ► miR-330 was inversely correlated with Cdc42 in colorectal cancer cells. ► Elevated miR-330 suppressed cell proliferation in vivo and in vitro. ► Elevated miR-330 mimicked the effect of Cdc42 knockdown. ► Restoration of Cdc42 could partially attenuate the effects of miR-330. -- Abstract: MicroRNAs are small non-coding RNA molecules that play important roles in the multistep process of colorectal carcinoma (CRC) development. However, the miRNA–mRNA regulatory network is far from being fully understood. The objective of this study was to investigate the expression and the biological roles of miR-330 in colorectal cancer cells. Cdc42, one of the best characterized members of the Rho GTPase family, was found to be up-regulated in several types of human tumors including CRC and has been implicated in cancer initiation and progression. In the present study, we identified miR-330, as a potential regulator of Cdc42, was found to be inversely correlated with Cdc42 expression in colorectal cancer cell lines. Ectopic expression of miR-330 down-regulated Cdc42 expression at both protein and mRNA level, mimicked the effect of Cdc42 knockdown in inhibiting proliferation, inducing G1 cell cycle arrest and apoptosis of the colorectal cancer cells, whereas restoration of Cdc42 could partially attenuate the effects of miR-330. In addition, elevated expression of miR-330 could suppress the immediate downstream effectors of Cdc42 and inhibit the growth of colorectal cancer cells in vivo. To sum up, our results establish a role of miR-330 in negatively regulating Cdc42 expression and colorectal cancer cell proliferation. They suggest that manipulating the expression level of Cdc42 by miR-330 has the potential to influence colorectal cancer progression.

  11. miR-330 regulates the proliferation of colorectal cancer cells by targeting Cdc42

    International Nuclear Information System (INIS)

    Li, Yuefeng; Zhu, Xiaolan; Xu, Wenlin; Wang, Dongqing; Yan, Jinchuan

    2013-01-01

    Highlights: ► miR-330 was inversely correlated with Cdc42 in colorectal cancer cells. ► Elevated miR-330 suppressed cell proliferation in vivo and in vitro. ► Elevated miR-330 mimicked the effect of Cdc42 knockdown. ► Restoration of Cdc42 could partially attenuate the effects of miR-330. -- Abstract: MicroRNAs are small non-coding RNA molecules that play important roles in the multistep process of colorectal carcinoma (CRC) development. However, the miRNA–mRNA regulatory network is far from being fully understood. The objective of this study was to investigate the expression and the biological roles of miR-330 in colorectal cancer cells. Cdc42, one of the best characterized members of the Rho GTPase family, was found to be up-regulated in several types of human tumors including CRC and has been implicated in cancer initiation and progression. In the present study, we identified miR-330, as a potential regulator of Cdc42, was found to be inversely correlated with Cdc42 expression in colorectal cancer cell lines. Ectopic expression of miR-330 down-regulated Cdc42 expression at both protein and mRNA level, mimicked the effect of Cdc42 knockdown in inhibiting proliferation, inducing G1 cell cycle arrest and apoptosis of the colorectal cancer cells, whereas restoration of Cdc42 could partially attenuate the effects of miR-330. In addition, elevated expression of miR-330 could suppress the immediate downstream effectors of Cdc42 and inhibit the growth of colorectal cancer cells in vivo. To sum up, our results establish a role of miR-330 in negatively regulating Cdc42 expression and colorectal cancer cell proliferation. They suggest that manipulating the expression level of Cdc42 by miR-330 has the potential to influence colorectal cancer progression

  12. Cdc42 is crucial for the establishment of epithelial polarity during early mammalian development

    DEFF Research Database (Denmark)

    Wu, Xunwei; Li, Shaohua; Chrostek-Grashoff, Anna

    2007-01-01

    To study the role of Cdc42 in the establishment of epithelial polarity during mammalian development, we generated murine Cdc42-null embryonic stem cells and analyzed peri-implantation development using embryoid bodies (EBs). Mutant EBs developed endoderm and underlying basement membrane, but exhi......To study the role of Cdc42 in the establishment of epithelial polarity during mammalian development, we generated murine Cdc42-null embryonic stem cells and analyzed peri-implantation development using embryoid bodies (EBs). Mutant EBs developed endoderm and underlying basement membrane...

  13. Cdc42 controls progenitor cell differentiation and beta-catenin turnover in skin

    DEFF Research Database (Denmark)

    Wu, Xunwei; Quondamatteo, Fabio; Lefever, Tine

    2006-01-01

    for differentiation of skin progenitor cells into HF lineage and that it regulates the turnover of beta-catenin. In the absence of Cdc42, degradation of beta-catenin was increased corresponding to a decreased phosphorylation of GSK3beta at Ser 9 and an increased phosphorylation of axin, which is known to be required...... for binding of beta-catenin to the degradation machinery. Cdc42-mediated regulation of beta-catenin turnover was completely dependent on PKCzeta, which associated with Cdc42, Par6, and Par3. These data suggest that Cdc42 regulation of beta-catenin turnover is important for terminal differentiation of HF...

  14. Primary angle closure glaucoma (PACG) susceptibility gene PLEKHA7 encodes a novel Rac1/Cdc42 GAP that modulates cell migration and blood-aqueous barrier function.

    Science.gov (United States)

    Lee, Mei-Chin; Shei, William; Chan, Anita S; Chua, Boon-Tin; Goh, Shuang-Ru; Chong, Yaan-Fun; Hilmy, Maryam H; Nongpiur, Monisha E; Baskaran, Mani; Khor, Chiea-Chuen; Aung, Tin; Hunziker, Walter; Vithana, Eranga N

    2017-10-15

    PLEKHA7, a gene recently associated with primary angle closure glaucoma (PACG), encodes an apical junctional protein expressed in components of the blood aqueous barrier (BAB). We found that PLEKHA7 is down-regulated in lens epithelial cells and in iris tissue of PACG patients. PLEKHA7 expression also correlated with the C risk allele of the sentinel SNP rs11024102 with the risk allele carrier groups having significantly reduced PLEKHA7 levels compared to non-risk allele carriers. Silencing of PLEKHA7 in human immortalized non-pigmented ciliary epithelium (h-iNPCE) and primary trabecular meshwork cells, which are intimately linked to BAB and aqueous humor outflow respectively, affected actin cytoskeleton organization. PLEKHA7 specifically interacts with GTP-bound Rac1 and Cdc42, but not RhoA, and the activation status of the two small GTPases is linked to PLEKHA7 expression levels. PLEKHA7 stimulates Rac1 and Cdc42 GTP hydrolysis, without affecting nucleotide exchange, identifying PLEKHA7 as a novel Rac1/Cdc42 GAP. Consistent with the regulatory role of Rac1 and Cdc42 in maintaining the tight junction permeability, silencing of PLEKHA7 compromises the paracellular barrier between h-iNPCE cells. Thus, downregulation of PLEKHA7 in PACG may affect BAB integrity and aqueous humor outflow via its Rac1/Cdc42 GAP activity, thereby contributing to disease etiology. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Rho GTPase protein Cdc42 is critical for postnatal cartilage development

    International Nuclear Information System (INIS)

    Nagahama, Ryo; Yamada, Atsushi; Tanaka, Junichi; Aizawa, Ryo; Suzuki, Dai; Kassai, Hidetoshi; Yamamoto, Matsuo; Mishima, Kenji; Aiba, Atsu; Maki, Koutaro; Kamijo, Ryutaro

    2016-01-01

    Cdc42, a small Rho GTPase family member, has been shown to regulate multiple cellular functions in vitro, including actin cytoskeletal reorganization, cell migration, proliferation, and gene expression. However, its tissue-specific roles in vivo remain largely unknown, especially in postnatal cartilage development, as cartilage-specific Cdc42 inactivated mice die within a few days after birth. In this study, we investigated the physiological functions of Cdc42 during cartilage development after birth using tamoxifen-induced cartilage-specific inactivated Cdc42 conditional knockout (Cdc42 "f"l"/"f"l; Col2-CreERT) mice, which were generated by crossing Cdc42 flox mice (Cdc42 "f"l"/"f"l) with tamoxifen-induced type II collagen (Col2) Cre transgenic mice using a Cre/loxP system. The gross morphology of the Cdc42 cKO mice was shorter limbs and body, as well as reduced body weight as compared with the controls. In addition, severe defects were found in growth plate chondrocytes of the long bones, characterized by a shorter proliferating zone (PZ), wider hypertrophic zone (HZ), and loss of columnar organization of proliferating chondrocytes, resulting in delayed endochondral bone formation associated with abnormal bone growth. Our findings demonstrate the importance of Cdc42 for cartilage development during both embryonic and postnatal stages. - Highlights: • Tamoxifen-induced cartilage specific inactivated Cdc42 mutant mice were generated. • Cdc42 mutant mice were shorter limbs and body. • Severe defects were found in growth plate chondrocytes.

  16. Rho GTPase protein Cdc42 is critical for postnatal cartilage development

    Energy Technology Data Exchange (ETDEWEB)

    Nagahama, Ryo [Department of Biochemistry, School of Dentistry, Showa University, Tokyo (Japan); Department of Orthodontics, School of Dentistry, Showa University, Tokyo (Japan); Yamada, Atsushi, E-mail: yamadaa@dent.showa-u.ac.jp [Department of Biochemistry, School of Dentistry, Showa University, Tokyo (Japan); Tanaka, Junichi [Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Tokyo (Japan); Aizawa, Ryo [Department of Periodontology, School of Dentistry, Showa University, Tokyo (Japan); Suzuki, Dai [Department of Biochemistry, School of Dentistry, Showa University, Tokyo (Japan); Kassai, Hidetoshi [Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo (Japan); Yamamoto, Matsuo [Department of Periodontology, School of Dentistry, Showa University, Tokyo (Japan); Mishima, Kenji [Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Tokyo (Japan); Aiba, Atsu [Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo (Japan); Maki, Koutaro [Department of Orthodontics, School of Dentistry, Showa University, Tokyo (Japan); Kamijo, Ryutaro [Department of Biochemistry, School of Dentistry, Showa University, Tokyo (Japan)

    2016-02-19

    Cdc42, a small Rho GTPase family member, has been shown to regulate multiple cellular functions in vitro, including actin cytoskeletal reorganization, cell migration, proliferation, and gene expression. However, its tissue-specific roles in vivo remain largely unknown, especially in postnatal cartilage development, as cartilage-specific Cdc42 inactivated mice die within a few days after birth. In this study, we investigated the physiological functions of Cdc42 during cartilage development after birth using tamoxifen-induced cartilage-specific inactivated Cdc42 conditional knockout (Cdc42 {sup fl/fl}; Col2-CreERT) mice, which were generated by crossing Cdc42 flox mice (Cdc42 {sup fl/fl}) with tamoxifen-induced type II collagen (Col2) Cre transgenic mice using a Cre/loxP system. The gross morphology of the Cdc42 cKO mice was shorter limbs and body, as well as reduced body weight as compared with the controls. In addition, severe defects were found in growth plate chondrocytes of the long bones, characterized by a shorter proliferating zone (PZ), wider hypertrophic zone (HZ), and loss of columnar organization of proliferating chondrocytes, resulting in delayed endochondral bone formation associated with abnormal bone growth. Our findings demonstrate the importance of Cdc42 for cartilage development during both embryonic and postnatal stages. - Highlights: • Tamoxifen-induced cartilage specific inactivated Cdc42 mutant mice were generated. • Cdc42 mutant mice were shorter limbs and body. • Severe defects were found in growth plate chondrocytes.

  17. Daphnetin inhibits invasion and migration of LM8 murine osteosarcoma cells by decreasing RhoA and Cdc42 expression

    Energy Technology Data Exchange (ETDEWEB)

    Fukuda, Hiroki [Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto (Japan); Nakamura, Seikou [Department of Pharmacognosy, Kyoto Pharmaceutical University, Kyoto (Japan); Chisaki, Yugo [Education and Research Center for Clinical Pharmacy, Kyoto Pharmaceutical University, Kyoto (Japan); Takada, Tetsuya [Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto (Japan); Toda, Yuki [Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Kyoto (Japan); Murata, Hiroaki [Department of Orthopedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan); Department of Orthopedic Surgery, Matsushita Memorial Hospital, Osaka (Japan); Itoh, Kazuyuki [Department of Biology, Osaka Medical Center of Cancer and Cardiovascular Diseases, Osaka (Japan); Yano, Yoshitaka [Education and Research Center for Clinical Pharmacy, Kyoto Pharmaceutical University, Kyoto (Japan); Takata, Kazuyuki [Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto (Japan); Ashihara, Eishi, E-mail: ash@mb.kyoto-phu.ac.jp [Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto (Japan)

    2016-02-26

    Daphnetin, 7,8-dihydroxycoumarin, present in main constituents of Daphne odora var. marginatai, has multiple pharmacological activities including anti-proliferative effects in cancer cells. In this study, using a Transwell system, we showed that daphnetin inhibited invasion and migration of highly metastatic murine osteosarcoma LM8 cells in a dose-dependent manner. Following treatment by daphnetin, cells that penetrated the Transwell membrane were rounder than non-treated cells. Immunofluorescence analysis revealed that daphnetin decreased the numbers of intracellular stress fibers and filopodia. Moreover, daphnetin treatment dramatically decreased the expression levels of RhoA and Cdc42. In summary, the dihydroxycoumarin derivative daphnetin inhibits the invasion and migration of LM8 cells, and therefore represents a promising agent for use against metastatic cancer. - Highlights: • Daphnetin, a coumarin-derivative, inhibited invasion and migration of LM8 cells. • Stress fibers and filopodia were decreased by daphnetin treatment. • Daphnetin decreased RhoA and Cdc42 protein expression.

  18. Daphnetin inhibits invasion and migration of LM8 murine osteosarcoma cells by decreasing RhoA and Cdc42 expression

    International Nuclear Information System (INIS)

    Fukuda, Hiroki; Nakamura, Seikou; Chisaki, Yugo; Takada, Tetsuya; Toda, Yuki; Murata, Hiroaki; Itoh, Kazuyuki; Yano, Yoshitaka; Takata, Kazuyuki; Ashihara, Eishi

    2016-01-01

    Daphnetin, 7,8-dihydroxycoumarin, present in main constituents of Daphne odora var. marginatai, has multiple pharmacological activities including anti-proliferative effects in cancer cells. In this study, using a Transwell system, we showed that daphnetin inhibited invasion and migration of highly metastatic murine osteosarcoma LM8 cells in a dose-dependent manner. Following treatment by daphnetin, cells that penetrated the Transwell membrane were rounder than non-treated cells. Immunofluorescence analysis revealed that daphnetin decreased the numbers of intracellular stress fibers and filopodia. Moreover, daphnetin treatment dramatically decreased the expression levels of RhoA and Cdc42. In summary, the dihydroxycoumarin derivative daphnetin inhibits the invasion and migration of LM8 cells, and therefore represents a promising agent for use against metastatic cancer. - Highlights: • Daphnetin, a coumarin-derivative, inhibited invasion and migration of LM8 cells. • Stress fibers and filopodia were decreased by daphnetin treatment. • Daphnetin decreased RhoA and Cdc42 protein expression.

  19. Podocyte-specific loss of cdc42 leads to congenital nephropathy

    DEFF Research Database (Denmark)

    Scott, Rizaldy P; Hawley, Steve P; Ruston, Julie

    2012-01-01

    in the absence of Cdc42, indicating a disruption of the slit diaphragm. Kidneys from Rac1- and RhoA-mutant mice, however, had normal glomerular morphology and intact foot processes. A nephrin clustering assay suggested that Cdc42 deficiency, but not Rac1 or RhoA deficiency, impairs the polymerization of actin...

  20. Multiple alterations of platelet functions dominated by increased secretion in mice lacking Cdc42 in platelets

    DEFF Research Database (Denmark)

    Pleines, Irina; Eckly, Anita; Elvers, Margitta

    2010-01-01

    formation and exocytosis in various cell types, but its exact function in platelets is not established. Here, we show that the megakaryocyte/platelet-specific loss of Cdc42 leads to mild thrombocytopenia and a small increase in platelet size in mice. Unexpectedly, Cdc42-deficient platelets were able to form...

  1. Involvement of the Cdc42 pathway in CFTR post-translational turnover and in its plasma membrane stability in airway epithelial cells.

    Directory of Open Access Journals (Sweden)

    Romain Ferru-Clément

    Full Text Available Cystic fibrosis transmembrane conductance regulator (CFTR is a chloride channel that is expressed on the apical plasma membrane (PM of epithelial cells. The most common deleterious allele encodes a trafficking-defective mutant protein undergoing endoplasmic reticulum-associated degradation (ERAD and presenting lower PM stability. In this study, we investigated the involvement of the Cdc42 pathway in CFTR turnover and trafficking in a human bronchiolar epithelial cell line (CFBE41o- expressing wild-type CFTR. Cdc42 is a small GTPase of the Rho family that fulfils numerous cell functions, one of which is endocytosis and recycling process via actin cytoskeleton remodelling. When we treated cells with chemical inhibitors such as ML141 against Cdc42 and wiskostatin against the downstream effector N-WASP, we observed that CFTR channel activity was inhibited, in correlation with a decrease in CFTR amount at the cell surface and an increase in dynamin-dependent CFTR endocytosis. Anchoring of CFTR to the cortical cytoskeleton was then presumably impaired by actin disorganization. When we performed siRNA-mediated depletion of Cdc42, actin polymerization was not impacted, but we observed actin-independent consequences upon CFTR. Total and PM CFTR amounts were increased, resulting in greater activation of CFTR. Pulse-chase experiments showed that while CFTR degradation was slowed, CFTR maturation through the Golgi apparatus remained unaffected. In addition, we observed increased stability of CFTR in PM and reduction of its endocytosis. This study highlights the involvement of the Cdc42 pathway at several levels of CFTR biogenesis and trafficking: (i Cdc42 is implicated in the first steps of CFTR biosynthesis and processing; (ii it contributes to the stability of CFTR in PM via its anchoring to cortical actin; (iii it promotes CFTR endocytosis and presumably its sorting toward lysosomal degradation.

  2. The Cdc42 guanine nucleotide exchange factor FGD6 coordinates cell polarity and endosomal membrane recycling in osteoclasts.

    Science.gov (United States)

    Steenblock, Charlotte; Heckel, Tobias; Czupalla, Cornelia; Espírito Santo, Ana Isabel; Niehage, Christian; Sztacho, Martin; Hoflack, Bernard

    2014-06-27

    The initial step of bone digestion is the adhesion of osteoclasts onto bone surfaces and the assembly of podosomal belts that segregate the bone-facing ruffled membrane from other membrane domains. During bone digestion, membrane components of the ruffled border also need to be recycled after macropinocytosis of digested bone materials. How osteoclast polarity and membrane recycling are coordinated remains unknown. Here, we show that the Cdc42-guanine nucleotide exchange factor FGD6 coordinates these events through its Src-dependent interaction with different actin-based protein networks. At the plasma membrane, FGD6 couples cell adhesion and actin dynamics by regulating podosome formation through the assembly of complexes comprising the Cdc42-interactor IQGAP1, the Rho GTPase-activating protein ARHGAP10, and the integrin interactors Talin-1/2 or Filamin A. On endosomes and transcytotic vesicles, FGD6 regulates retromer-dependent membrane recycling through its interaction with the actin nucleation-promoting factor WASH. These results provide a mechanism by which a single Cdc42-exchange factor controlling different actin-based processes coordinates cell adhesion, cell polarity, and membrane recycling during bone degradation. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Different roles of the small GTPases Rac1, Cdc42, and RhoG in CALEB/NGC-induced dendritic tree complexity.

    Science.gov (United States)

    Schulz, Jana; Franke, Kristin; Frick, Manfred; Schumacher, Stefan

    2016-10-01

    Rho GTPases play prominent roles in the regulation of cytoskeletal reorganization. Many aspects have been elaborated concerning the individual functions of Rho GTPases in distinct signaling pathways leading to cytoskeletal rearrangements. However, major questions have yet to be answered regarding the integration and the signaling hierarchy of different Rho GTPases in regulating the cytoskeleton in fundamental physiological events like neuronal process differentiation. Here, we investigate the roles of the small GTPases Rac1, Cdc42, and RhoG in defining dendritic tree complexity stimulated by the transmembrane epidermal growth factor family member CALEB/NGC. Combining gain-of-function and loss-of-function analysis in primary hippocampal neurons, we find that Rac1 is essential for CALEB/NGC-mediated dendritic branching. Cdc42 reduces the complexity of dendritic trees. Interestingly, we identify the palmitoylated isoform of Cdc42 to adversely affect dendritic outgrowth and dendritic branching, whereas the prenylated Cdc42 isoform does not. In contrast to Rac1, CALEB/NGC and Cdc42 are not directly interconnected in regulating dendritic tree complexity. Unlike Rac1, the Rac1-related GTPase RhoG reduces the complexity of dendritic trees by acting upstream of CALEB/NGC. Mechanistically, CALEB/NGC activates Rac1, and RhoG reduces the amount of CALEB/NGC that is located at the right site for Rac1 activation at the cell membrane. Thus, Rac1, Cdc42, and RhoG perform very specific and non-redundant functions at different levels of hierarchy in regulating dendritic tree complexity induced by CALEB/NGC. Rho GTPases play a prominent role in dendritic branching. CALEB/NGC is a transmembrane member of the epidermal growth factor (EGF) family that mediates dendritic branching, dependent on Rac1. CALEB/NGC stimulates Rac1 activity. RhoG inhibits CALEB/NGC-mediated dendritic branching by decreasing the amount of CALEB/NGC at the plasma membrane. Palmitoylated, but not prenylated form

  4. Cdc42 is a key regulator of B cell differentiation and is required for antiviral humoral immunity

    DEFF Research Database (Denmark)

    Burbage, Marianne; Keppler, Selina J; Gasparrini, Francesca

    2015-01-01

    The small Rho GTPase Cdc42, known to interact with Wiskott-Aldrich syndrome (WAS) protein, is an important regulator of actin remodeling. Here, we show that genetic ablation of Cdc42 exclusively in the B cell lineage is sufficient to render mice unable to mount antibody responses. Indeed Cdc42-de...

  5. Synapse Formation in Monosynaptic Sensory–Motor Connections Is Regulated by Presynaptic Rho GTPase Cdc42

    Science.gov (United States)

    Imai, Fumiyasu; Ladle, David R.; Leslie, Jennifer R.; Duan, Xin; Rizvi, Tilat A.; Ciraolo, Georgianne M.; Zheng, Yi

    2016-01-01

    Spinal reflex circuit development requires the precise regulation of axon trajectories, synaptic specificity, and synapse formation. Of these three crucial steps, the molecular mechanisms underlying synapse formation between group Ia proprioceptive sensory neurons and motor neurons is the least understood. Here, we show that the Rho GTPase Cdc42 controls synapse formation in monosynaptic sensory–motor connections in presynaptic, but not postsynaptic, neurons. In mice lacking Cdc42 in presynaptic sensory neurons, proprioceptive sensory axons appropriately reach the ventral spinal cord, but significantly fewer synapses are formed with motor neurons compared with wild-type mice. Concordantly, electrophysiological analyses show diminished EPSP amplitudes in monosynaptic sensory–motor circuits in these mutants. Temporally targeted deletion of Cdc42 in sensory neurons after sensory–motor circuit establishment reveals that Cdc42 does not affect synaptic transmission. Furthermore, addition of the synaptic organizers, neuroligins, induces presynaptic differentiation of wild-type, but not Cdc42-deficient, proprioceptive sensory neurons in vitro. Together, our findings demonstrate that Cdc42 in presynaptic neurons is required for synapse formation in monosynaptic sensory–motor circuits. SIGNIFICANCE STATEMENT Group Ia proprioceptive sensory neurons form direct synapses with motor neurons, but the molecular mechanisms underlying synapse formation in these monosynaptic sensory–motor connections are unknown. We show that deleting Cdc42 in sensory neurons does not affect proprioceptive sensory axon targeting because axons reach the ventral spinal cord appropriately, but these neurons form significantly fewer presynaptic terminals on motor neurons. Electrophysiological analysis further shows that EPSPs are decreased in these mice. Finally, we demonstrate that Cdc42 is involved in neuroligin-dependent presynaptic differentiation of proprioceptive sensory neurons in vitro

  6. Cdc42 expression in keratinocytes is required for the maintenance of the basement membrane in skin

    DEFF Research Database (Denmark)

    Wu, Xunwei; Quondamatteo, Fabio; Brakebusch, Cord

    2006-01-01

    , structure and number of hemidesomosomes were not significantly changed in the Cdc42 mutant skin compared with the control mice and no blister formation was observed in mutant skin. These data indicate that Cdc42 in keratinocytes is important for maintenance of the basement membrane of skin....... process, which requires directed secretion, deposition and organization of basement membrane components at the basal side of epithelial cells. In the current study, we analyzed the maintenance of skin basement membrane in mice with a keratinocyte-restricted deletion of the Cdc42 gene. In the absence...

  7. Cdc42 and phosphoinositide 3-kinase drive Rac-mediated actin polymerization downstream of c-Met in distinct and common pathways

    DEFF Research Database (Denmark)

    Bosse, Tanja; Ehinger, Julia; Czuchra, Aleksandra

    2007-01-01

    -WASP. Instead, actin polymerization was driven by Arp2/3 complex activation through the WAVE complex downstream of Rac. Together, our data establish an intricate signaling network comprising as key molecules Cdc42 and PI3-kinase, which converge on Rac-mediated actin reorganization essential for Listeria...

  8. Caveolin-1 and CDC42 mediated endocytosis of silica-coated iron oxide nanoparticles in HeLa cells

    Directory of Open Access Journals (Sweden)

    Nils Bohmer

    2015-01-01

    Full Text Available Nanomedicine is a rapidly growing field in nanotechnology, which has great potential in the development of new therapies for numerous diseases. For example iron oxide nanoparticles are in clinical use already in the thermotherapy of brain cancer. Although it has been shown, that tumor cells take up these particles in vitro, little is known about the internalization routes. Understanding of the underlying uptake mechanisms would be very useful for faster and precise development of nanoparticles for clinical applications. This study aims at the identification of key proteins, which are crucial for the active uptake of iron oxide nanoparticles by HeLa cells (human cervical cancer as a model cell line. Cells were transfected with specific siRNAs against Caveolin-1, Dynamin 2, Flotillin-1, Clathrin, PIP5Kα and CDC42. Knockdown of Caveolin-1 reduces endocytosis of superparamagnetic iron oxide nanoparticles (SPIONs and silica-coated iron oxide nanoparticles (SCIONs between 23 and 41%, depending on the surface characteristics of the nanoparticles and the experimental design. Knockdown of CDC42 showed a 46% decrease of the internalization of PEGylated SPIONs within 24 h incubation time. Knockdown of Dynamin 2, Flotillin-1, Clathrin and PIP5Kα caused no or only minor effects. Hence endocytosis in HeLa cells of iron oxide nanoparticles, used in this study, is mainly mediated by Caveolin-1 and CDC42. It is shown here for the first time, which proteins of the endocytotic pathway mediate the endocytosis of silica-coated iron oxide nanoparticles in HeLa cells in vitro. In future studies more experiments should be carried out with different cell lines and other well-defined nanoparticle species to elucidate possible general principles.

  9. Divergent functions of the Rho GTPases Rac1 and Cdc42 in podocyte injury

    DEFF Research Database (Denmark)

    Blattner, Simone M; Hodgin, Jeffrey B; Nishio, Masashi

    2013-01-01

    -specific deletion of Rac1 prevented foot process effacement. In a long-term model of chronic hypertensive glomerular damage, however, loss of Rac1 led to an exacerbation of albuminuria and glomerulosclerosis. In contrast, mice with podocyte-specific deletion of Cdc42 had severe proteinuria, podocyte foot process...... effacement, and glomerulosclerosis beginning as early as 10 days of age. In addition, slit diaphragm proteins nephrin and podocin were redistributed, and cofilin was dephosphorylated. Cdc42 is necessary for the maintenance of podocyte structure and function, but Rac1 is entirely dispensable in physiological...... steady state. However, Rac1 has either beneficial or deleterious effects depending on the context of podocyte impairment. Thus, our study highlights the divergent roles of Rac1 and Cdc42 function in podocyte maintenance and injury.Kidney International advance online publication, 15 May 2013; doi:10...

  10. The small G-proteins Rac1 and Cdc42 are essential for myoblast fusion in the mouse

    DEFF Research Database (Denmark)

    Vasyutina, Elena; Martarelli, Benedetta; Brakebusch, Cord

    2009-01-01

    Rac1 and Cdc42 are small G-proteins that regulate actin dynamics and affect plasma membrane protrusion and vesicle traffic. We used conditional mutagenesis in mice to demonstrate that Rac1 and Cdc42 are essential for myoblast fusion in vivo and in vitro. The deficit in fusion of Rac1 or Cdc42 mut...... genetic analysis demonstrates thus that the function of Rac in myoblast fusion is evolutionarily conserved from insects to mammals and that Cdc42, a molecule hitherto not implicated in myoblast fusion, is essential for the fusion of murine myoblasts....

  11. Active surveillance strategy for patients with localised prostate cancer

    DEFF Research Database (Denmark)

    Thomsen, Frederik Birkebæk

    2014-01-01

    BACKGROUND: Active surveillance - an initial observational strategy - offers a tailored management of patients with localised prostate cancer. The aim of the strategy is to appoint patients with potentially lethal prostate cancer to curatively intended treatment, while patients with slowly evolving...... measurements, repeated biopsies, and regular digital rectal examinations. The programme recommended change of management from active surveillance to curatively intended treatment based on PSA doubling time, deteriorating histopathology in repeated prostatic biopsies, and increased clinical tumour category...... with defined final histopathological findings at radical prostatectomy that was perceived as unacceptable for a continued observational strategy. CONCLUSION: The thesis has demonstrated that active surveillance is feasible and reduces the number of patients undergoing curative intended treatment. However...

  12. Continuous cell injury promotes hepatic tumorigenesis in cdc42-deficient mouse liver

    DEFF Research Database (Denmark)

    van Hengel, Jolanda; D'Hooge, Petra; Hooghe, Bart

    2008-01-01

    be required for liver function. METHODS: Mice in which Cdc42 was ablated in hepatocytes and bile duct cells were generated by Cre-loxP technology. Livers were examined by histologic, immunohistochemical, ultrastructural, and serum analysis to define the effect of loss of Cdc42 on liver structure. RESULTS...... of 2 months, the canaliculi between hepatocytes were greatly enlarged, although the tight junctions flanking the canaliculi appeared normal. Regular liver plates were absent. E-cadherin expression pattern and gap junction localization were distorted. Analysis of serum samples indicated cholestasis...

  13. Role of TGF-beta1-independent changes in protein neosynthesis, p38alphaMAPK, and cdc42 in hydrogen peroxide-induced senescence-like morphogenesis

    DEFF Research Database (Denmark)

    Chrétien, Aline; Dierick, Jean-François; Delaive, Edouard

    2008-01-01

    for p38(MAPK) activation, in turn triggering phosphorylation of L-caldesmon and HSP27. Cdc42 was also shown to be mainly responsible for the increase in TGF-beta1 mRNA level observed at 24 h after treatment with H(2)O(2) and onward. This study further clarified the mechanisms of senescence......The role of TGF-beta1 in hydrogen peroxide-induced senescence-like morphogenesis has been described. The aim of this work was to investigate whether TGF-beta1-independent changes in protein synthesis are involved in this morphogenesis and to study possible mechanisms occurring earlier than TGF-beta......1 overexpression. Among the multiple TGF-beta1-independent changes in protein neosynthesis, followed or not by posttranslational modifications, identified by proteomic analysis herein, those of ezrin, L-caldesmon, and HSP27 were particularly studied. Rho-GTPase cdc42 was shown to be responsible...

  14. FMNL2 and -3 regulate Golgi architecture and anterograde transport downstream of Cdc42

    DEFF Research Database (Denmark)

    Kage, Frieda; Steffen, Anika; Ellinger, Adolf

    2017-01-01

    The Rho-family small GTPase Cdc42 localizes at plasma membrane and Golgi complex and aside from protrusion and migration operates in vesicle trafficking, endo- and exocytosis as well as establishment and/or maintenance of cell polarity. The formin family members FMNL2 and -3 are actin assembly fa...

  15. Cdc42-dependent structural development of auditory supporting cells is required for wound healing at adulthood

    DEFF Research Database (Denmark)

    Anttonen, Tommi; Kirjavainen, Anna; Belevich, Ilya

    2012-01-01

    of a basolateral membrane protein in the apical domain were observed. These defects and changes in aPKCλ/ι expression suggested that apical polarization is impaired. Following a lesion at adulthood, supporting cells with Cdc42 loss-induced maturational defects collapsed and failed to remodel F-actin belts...

  16. Cdc42 is not essential for filopodium formation, directed migration, cell polarization, and mitosis in fibroblastoid cells

    DEFF Research Database (Denmark)

    Czuchra, Aleksandra; Wu, Xunwei; Meyer, Hannelore

    2005-01-01

    of Cdc42 did not affect filopodium or lamellipodium formation and had no significant influence on the speed of directed migration nor on mitosis. Cdc42-deficient cells displayed a more elongated cell shape and had a reduced area. Furthermore, directionality during migration and reorientation of the Golgi...

  17. A TOCA/CDC-42/PAR/WAVE functional module required for retrograde endocytic recycling

    Science.gov (United States)

    Bai, Zhiyong; Grant, Barth D.

    2015-01-01

    Endosome-to-Golgi transport is required for the function of many key membrane proteins and lipids, including signaling receptors, small-molecule transporters, and adhesion proteins. The retromer complex is well-known for its role in cargo sorting and vesicle budding from early endosomes, in most cases leading to cargo fusion with the trans-Golgi network (TGN). Transport from recycling endosomes to the TGN has also been reported, but much less is understood about the molecules that mediate this transport step. Here we provide evidence that the F-BAR domain proteins TOCA-1 and TOCA-2 (Transducer of Cdc42 dependent actin assembly), the small GTPase CDC-42 (Cell division control protein 42), associated polarity proteins PAR-6 (Partitioning defective 6) and PKC-3/atypical protein kinase C, and the WAVE actin nucleation complex mediate the transport of MIG-14/Wls and TGN-38/TGN38 cargo proteins from the recycling endosome to the TGN in Caenorhabditis elegans. Our results indicate that CDC-42, the TOCA proteins, and the WAVE component WVE-1 are enriched on RME-1–positive recycling endosomes in the intestine, unlike retromer components that act on early endosomes. Furthermore, we find that retrograde cargo TGN-38 is trapped in early endosomes after depletion of SNX-3 (a retromer component) but is mainly trapped in recycling endosomes after depletion of CDC-42, indicating that the CDC-42–associated complex functions after retromer in a distinct organelle. Thus, we identify a group of interacting proteins that mediate retrograde recycling, and link these proteins to a poorly understood trafficking step, recycling endosome-to-Golgi transport. We also provide evidence for the physiological importance of this pathway in WNT signaling. PMID:25775511

  18. Suppression of chemotaxis by SSeCKS via scaffolding of phosphoinositol phosphates and the recruitment of the Cdc42 GEF, Frabin, to the leading edge.

    Science.gov (United States)

    Ko, Hyun-Kyung; Guo, Li-wu; Su, Bing; Gao, Lingqiu; Gelman, Irwin H

    2014-01-01

    Chemotaxis is controlled by interactions between receptors, Rho-family GTPases, phosphatidylinositol 3-kinases, and cytoskeleton remodeling proteins. We investigated how the metastasis suppressor, SSeCKS, attenuates chemotaxis. Chemotaxis activity inversely correlated with SSeCKS levels in mouse embryo fibroblasts (MEF), DU145 and MDA-MB-231 cancer cells. SSeCKS loss induced chemotactic velocity and linear directionality, correlating with replacement of leading edge lamellipodia with fascin-enriched filopodia-like extensions, the formation of thickened longitudinal F-actin stress fibers reaching to filopodial tips, relative enrichments at the leading edge of phosphatidylinositol (3,4,5)P3 (PIP3), Akt, PKC-ζ, Cdc42-GTP and active Src (SrcpoY416), and a loss of Rac1. Leading edge lamellipodia and chemotaxis inhibition in SSeCKS-null MEF could be restored by full-length SSeCKS or SSeCKS deleted of its Src-binding domain (ΔSrc), but not by SSeCKS deleted of its three MARCKS (myristylated alanine-rich C kinase substrate) polybasic domains (ΔPBD), which bind PIP2 and PIP3. The enrichment of activated Cdc42 in SSeCKS-null leading edge filopodia correlated with recruitment of the Cdc42-specific guanine nucleotide exchange factor, Frabin, likely recruited via multiple PIP2/3-binding domains. Frabin knockdown in SSeCKS-null MEF restores leading edge lamellipodia and chemotaxis inhibition. However, SSeCKS failed to co-immunoprecipitate with Rac1, Cdc42 or Frabin. Consistent with the notion that chemotaxis is controlled by SSeCKS-PIP (vs. -Src) scaffolding activity, constitutively-active phosphatidylinositol 3-kinase could override the ability of the Src inhibitor, SKI-606, to suppress chemotaxis and filopodial enrichment of Frabin in SSeCKS-null MEF. Our data suggest a role for SSeCKS in controlling Rac1 vs. Cdc42-induced cellular dynamics at the leading chemotactic edge through the scaffolding of phospholipids and signal mediators, and through the reorganization of the

  19. The Rho GTPase Cdc42 regulates hair cell planar polarity and cellular patterning in the developing cochlea

    Directory of Open Access Journals (Sweden)

    Anna Kirjavainen

    2015-03-01

    Full Text Available Hair cells of the organ of Corti (OC of the cochlea exhibit distinct planar polarity, both at the tissue and cellular level. Planar polarity at tissue level is manifested as uniform orientation of the hair cell stereociliary bundles. Hair cell intrinsic polarity is defined as structural hair bundle asymmetry; positioning of the kinocilium/basal body complex at the vertex of the V-shaped bundle. Consistent with strong apical polarity, the hair cell apex displays prominent actin and microtubule cytoskeletons. The Rho GTPase Cdc42 regulates cytoskeletal dynamics and polarization of various cell types, and, thus, serves as a candidate regulator of hair cell polarity. We have here induced Cdc42 inactivation in the late-embryonic OC. We show the role of Cdc42 in the establishment of planar polarity of hair cells and in cellular patterning. Abnormal planar polarity was displayed as disturbances in hair bundle orientation and morphology and in kinocilium/basal body positioning. These defects were accompanied by a disorganized cell-surface microtubule network. Atypical protein kinase C (aPKC, a putative Cdc42 effector, colocalized with Cdc42 at the hair cell apex, and aPKC expression was altered upon Cdc42 depletion. Our data suggest that Cdc42 together with aPKC is part of the machinery establishing hair cell planar polarity and that Cdc42 acts on polarity through the cell-surface microtubule network. The data also suggest that defects in apical polarization are influenced by disturbed cellular patterning in the OC. In addition, our data demonstrates that Cdc42 is required for stereociliogenesis in the immature cochlea.

  20. Defective tubulin organization and proplatelet formation in murine megakaryocytes lacking Rac1 and Cdc42

    DEFF Research Database (Denmark)

    Pleines, Irina; Dütting, Sebastian; Cherpokova, Deya

    2013-01-01

    Blood platelets are anuclear cell fragments that are essential for blood clotting. Platelets are produced by bone marrow megakaryocytes (MKs), which extend protrusions, or so-called proplatelets, into bone marrow sinusoids. Proplatelet formation requires a profound reorganization of the MK actin...... normally in vivo but displayed highly abnormal morphology and uncontrolled fragmentation. Consistently, a lack of Rac1/Cdc42 virtually abrogated proplatelet formation in vitro. Strikingly, this phenotype was associated with severely defective tubulin organization, whereas actin assembly and structure were...

  1. Genetic deletion of cdc42 reveals a crucial role for astrocyte recruitment to the injury site in vitro and in vivo

    DEFF Research Database (Denmark)

    Robel, Stefanie; Bardehle, Sophia; Lepier, Alexandra

    2011-01-01

    signals, the small RhoGTPase Cdc42, selectively in mouse astrocytes in vitro and in vivo. We used an in vitro scratch assay as a minimal wounding model and found that astrocytes lacking Cdc42 (Cdc42Δ) were still able to form protrusions, although in a nonoriented way. Consequently, they failed to migrate...... in a directed manner toward the scratch. When animals were injured in vivo through a stab wound, Cdc42Δ astrocytes developed protrusions properly oriented toward the lesion, but the number of astrocytes recruited to the lesion site was significantly reduced. Surprisingly, however, lesions in Cdc42Δ animals...

  2. Ang II-AT2R increases mesenchymal stem cell migration by signaling through the FAK and RhoA/Cdc42 pathways in vitro.

    Science.gov (United States)

    Xu, Xiu-Ping; He, Hong-Li; Hu, Shu-Ling; Han, Ji-Bin; Huang, Li-Li; Xu, Jing-Yuan; Xie, Jian-Feng; Liu, Ai-Ran; Yang, Yi; Qiu, Hai-Bo

    2017-07-12

    Mesenchymal stem cells (MSCs) migrate via the bloodstream to sites of injury and are possibly attracted by inflammatory factors. As a proinflammatory mediator, angiotensin II (Ang II) reportedly enhances the migration of various cell types by signaling via the Ang II receptor in vitro. However, few studies have focused on the effects of Ang II on MSC migration and the underlying mechanisms. Human bone marrow MSCs migration was measured using wound healing and Boyden chamber migration assays after treatments with different concentrations of Ang II, an AT1R antagonist (Losartan), and/or an AT2R antagonist (PD-123319). To exclude the effect of proliferation on MSC migration, we measured MSC proliferation after stimulation with the same concentration of Ang II. Additionally, we employed the focal adhesion kinase (FAK) inhibitor PF-573228, RhoA inhibitor C3 transferase, Rac1 inhibitor NSC23766, or Cdc42 inhibitor ML141 to investigate the role of cell adhesion proteins and the Rho-GTPase protein family (RhoA, Rac1, and Cdc42) in Ang II-mediated MSC migration. Cell adhesion proteins (FAK, Talin, and Vinculin) were detected by western blot analysis. The Rho-GTPase family protein activities were assessed by G-LISA and F-actin levels, which reflect actin cytoskeletal organization, were detected by using immunofluorescence. Human bone marrow MSCs constitutively expressed AT1R and AT2R. Additionally, Ang II increased MSC migration in an AT2R-dependent manner. Notably, Ang II-enhanced migration was not mediated by Ang II-mediated cell proliferation. Interestingly, Ang II-enhanced migration was mediated by FAK activation, which was critical for the formation of focal contacts, as evidenced by increased Talin and Vinculin expression. Moreover, RhoA and Cdc42 were activated by FAK to increase cytoskeletal organization, thus promoting cell contraction. Furthermore, FAK, Talin, and Vinculin activation and F-actin reorganization in response to Ang II were prevented by PD-123319 but

  3. Stage-specific functions of the small Rho GTPases Cdc42 and Rac1 for adult hippocampal neurogenesis

    DEFF Research Database (Denmark)

    Vadodaria, Krishna C; Brakebusch, Cord; Suter, Ueli

    2013-01-01

    The molecular mechanisms underlying the generation, maturation, and integration of new granule cells generated throughout life in the mammalian hippocampus remain poorly understood. Small Rho GTPases, such as Cdc42 and Rac1, have been implicated previously in neural stem/progenitor cell (NSPC......) proliferation and neuronal maturation during embryonic development. Here we used conditional genetic deletion and virus-based loss-of-function approaches to identify temporally distinct functions for Cdc42 and Rac1 in adult hippocampal neurogenesis. We found that Cdc42 is involved in mouse NSPC proliferation......, initial dendritic development, and dendritic spine maturation. In contrast, Rac1 is dispensable for early steps of neuronal development but is important for late steps of dendritic growth and spine maturation. These results establish cell-autonomous and stage-specific functions for the small Rho GTPases...

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

    Science.gov (United States)

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

    2016-12-06

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

  5. How active ingredient localisation in plant tissues determines the targeted pest spectrum of different chemistries

    DEFF Research Database (Denmark)

    Buchholz, Anke; Trapp, Stefan

    2016-01-01

    information sets revealed that the intracellular localisation of active ingredients determines the performance of test compounds against different target pests because of different feeding behaviours: mites feed on mesophyll, and aphids and whiteflies mostly in the vascular system. Polar compounds have a slow...

  6. Control of ADAM17 activity by regulation of its cellular localisation

    Science.gov (United States)

    Lorenzen, Inken; Lokau, Juliane; Korpys, Yvonne; Oldefest, Mirja; Flynn, Charlotte M.; Künzel, Ulrike; Garbers, Christoph; Freeman, Matthew; Grötzinger, Joachim; Düsterhöft, Stefan

    2016-01-01

    An important, irreversible step in many signalling pathways is the shedding of membrane-anchored proteins. A Disintegrin And Metalloproteinase (ADAM) 17 is one of the major sheddases involved in a variety of physiological and pathophysiological processes including regeneration, differentiation, and cancer progression. This central role in signalling implies that ADAM17 activity has to be tightly regulated, including at the level of localisation. Most mature ADAM17 is localised intracellularly, with only a small amount at the cell surface. We found that ADAM17 is constitutively internalised by clathrin-coated pits and that physiological stimulators such as GPCR ligands induce ADAM17-mediated shedding, but do not alter the cell-surface abundance of the protease. In contrast, the PKC-activating phorbol ester PMA, often used as a strong inducer of ADAM17, causes not only proteolysis by ADAM17 but also a rapid increase of the mature protease at the cell surface. This is followed by internalisation and subsequent degradation of the protease. Eventually, this leads to a substantial downregulation of mature ADAM17. Our results therefore imply that physiological activation of ADAM17 does not rely on its relocalisation, but that PMA-induced PKC activity drastically dysregulates the localisation of ADAM17. PMID:27731361

  7. Automaticity and localisation of concurrents predicts colour area activity in grapheme-colour synaesthesia.

    Science.gov (United States)

    Gould van Praag, Cassandra D; Garfinkel, Sarah; Ward, Jamie; Bor, Daniel; Seth, Anil K

    2016-07-29

    In grapheme-colour synaesthesia (GCS), the presentation of letters or numbers induces an additional 'concurrent' experience of colour. Early functional MRI (fMRI) investigations of GCS reported activation in colour-selective area V4 during the concurrent experience. However, others have failed to replicate this key finding. We reasoned that individual differences in synaesthetic phenomenology might explain this inconsistency in the literature. To test this hypothesis, we examined fMRI BOLD responses in a group of grapheme-colour synaesthetes (n=20) and matched controls (n=20) while characterising the individual phenomenology of the synaesthetes along dimensions of 'automaticity' and 'localisation'. We used an independent functional localiser to identify colour-selective areas in both groups. Activations in these areas were then assessed during achromatic synaesthesia-inducing, and non-inducing conditions; we also explored whole brain activations, where we sought to replicate the existing literature regarding synaesthesia effects. Controls showed no significant activations in the contrast of inducing > non-inducing synaesthetic stimuli, in colour-selective ROIs or at the whole brain level. In the synaesthete group, we correlated activation within colour-selective ROIs with individual differences in phenomenology using the Coloured Letters and Numbers (CLaN) questionnaire which measures, amongst other attributes, the subjective automaticity/attention in synaesthetic concurrents, and their spatial localisation. Supporting our hypothesis, we found significant correlations between individual measures of synaesthetic phenomenology and BOLD responses in colour-selective areas, when contrasting inducing against non-inducing stimuli. Specifically, left-hemisphere colour area responses were stronger for synaesthetes scoring high on phenomenological localisation and automaticity/attention, while right-hemisphere colour area responses showed a relationship with localisation

  8. Stage-specific control of neural crest stem cell proliferation by the small rho GTPases Cdc42 and Rac1

    DEFF Research Database (Denmark)

    Fuchs, Sebastian; Herzog, Dominik; Sumara, Grzegorz

    2009-01-01

    -renewal and proliferation of later stage, but not early migratory NCSCs. This stage-specific requirement for small Rho GTPases is due to changes in NCSCs that, during development, acquire responsiveness to mitogenic EGF acting upstream of both Cdc42 and Rac1. Thus, our data reveal distinct mechanisms for growth control......The neural crest (NC) generates a variety of neural and non-neural tissues during vertebrate development. Both migratory NC cells and their target structures contain cells with stem cell features. Here we show that these populations of neural crest-derived stem cells (NCSCs) are differentially...

  9. A hot-spot mutation in CDC42 (p.Tyr64Cys) and novel phenotypes in the third patient with Takenouchi-Kosaki syndrome.

    Science.gov (United States)

    Motokawa, Midori; Watanabe, Satoshi; Nakatomi, Akiko; Kondoh, Tatsuro; Matsumoto, Tadashi; Morifuji, Kanako; Sawada, Hirotake; Nishimura, Toyoki; Nunoi, Hiroyuki; Yoshiura, Koh-Ichiro; Moriuchi, Hiroyuki; Dateki, Sumito

    2018-03-01

    Takenouchi-Kosaki syndrome (TKS) is a congenital malformation syndrome characterized by severe developmental delay, macrothrombocytopenia, camptodactyly, sensorineural hearing loss, and dysmorphic facial features. Recently, a heterozygous de novo mutation (p.Tyr64Cys) in the CDC42 gene, which encodes a key small GTP-binding protein of the Rho-subfamily, was identified in two unrelated patients with TKS. We herein report a third patient with TKS who had the same heterozygous CDC42 mutation. The phenotype of the patient was very similar to those of the two previously reported patients with TKS; however, she also demonstrated novel clinical manifestations, such as congenital hypothyroidism and immunological disturbance. Thus, despite the heterozygous mutation of CDC42 (p.Tyr64Cys) likely being a hot-spot mutation for TKS, its phenotype may be variable. Further studies and the accumulation of patients with CDC42 mutations are needed to clarify the phenotype in patients with TKS and the pathophysiological roles of the CDC42 mutation.

  10. Tissue level, activation and cellular localisation of TGF-β1 and association with survival in gastric cancer patients

    NARCIS (Netherlands)

    Hawinkels, L.J.A.C.; Verspaget, H.W.; Duijn, W. van; Zon, J.M. van der; Zuidwijk, K.; Kubben, F.J.G.M.; Verheijen, J.H.; Hommes, D.W.; Lamers, C.B.H.W.; Sier, C.F.M.

    2007-01-01

    Transforming growth factor-β1 (TGF-β1), a tumour suppressing as well as tumour-promoting cytokine, is stored as an extracellular matrix-bound latent complex. We examined TGF-β1 activation and localisation of TGF-β1 activity in gastric cancer. Gastric tumours showed increased stromal and epithelial

  11. Vasoactive intestinal peptide-induced neurite remodeling in human neuroblastoma SH-SY5Y cells implicates the Cdc42 GTPase and is independent of Ras-ERK pathway

    International Nuclear Information System (INIS)

    Alleaume, Celine; Eychene, Alain; Harnois, Thomas; Bourmeyster, Nicolas; Constantin, Bruno; Caigneaux, Evelyne; Muller, Jean-Marc; Philippe, Michel

    2004-01-01

    Vasoactive intestinal peptide (VIP) is known to regulate proliferation or differentiation in normal and tumoral cells. SH-SY5Y is a differentiated cell subclone derived from the SK-N-SH human neuroblastoma cell line and possess all the components for an autocrine action of VIP. In the present study, we investigated the morphological changes and intracellular signaling pathways occurring upon VIP treatment of SH-SY5Y cells. VIP induced an early remodeling of cell projections: a branched neurite network spread out and prominent varicosities developed along neurites. Although activated by VIP, the Ras/ERK pathway was not required for the remodeling process. In contrast, pull-down experiments revealed a strong Cdc42 activation by VIP while expression of a dominant-negative Cdc42 prevented the VIP-induced neurite changes, suggesting an important role for this small GTPase in the process. These data provide the first evidence for a regulation of the activity of Rho family GTPases by VIP and bring new insights in the signaling pathways implicated in neurite remodeling process induced by VIP in neuroblastoma cells

  12. Activation of multiple chemotherapeutic prodrugs by the natural enzymolome of tumour-localised probiotic bacteria.

    Science.gov (United States)

    Lehouritis, Panos; Stanton, Michael; McCarthy, Florence O; Jeavons, Matthieu; Tangney, Mark

    2016-01-28

    Some chemotherapeutic drugs (prodrugs) require activation by an enzyme for efficacy. We and others have demonstrated the ability of probiotic bacteria to grow specifically within solid tumours following systemic administration, and we hypothesised that the natural enzymatic activity of these tumour-localised bacteria may be suitable for activation of certain such chemotherapeutic drugs. Several wild-type probiotic bacteria; Escherichia coli Nissle, Bifidobacterium breve, Lactococcus lactis and Lactobacillus species, were screened against a panel of popular prodrugs. All strains were capable of activating at least one prodrug. E. coli Nissle 1917 was selected for further studies because of its ability to activate numerous prodrugs and its resistance to prodrug toxicity. HPLC data confirmed biochemical transformation of prodrugs to their toxic counterparts. Further analysis demonstrated that different enzymes can complement prodrug activation, while simultaneous activation of multiple prodrugs (CB1954, 5-FC, AQ4N and Fludarabine phosphate) by E. coli was confirmed, resulting in significant efficacy improvement. Experiments in mice harbouring murine tumours validated in vitro findings, with significant reduction in tumour growth and increase in survival of mice treated with probiotic bacteria and a combination of prodrugs. These findings demonstrate the ability of probiotic bacteria, without the requirement for genetic modification, to enable high-level activation of multiple prodrugs specifically at the site of action. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Piezoelectric ceramic (PZT) modulates axonal guidance growth of rat cortical neurons via RhoA, Rac1, and Cdc42 pathways.

    Science.gov (United States)

    Wen, Jianqiang; Liu, Meili

    2014-03-01

    Electrical stimulation is critical for axonal connection, which can stimulate axonal migration and deformation to promote axonal growth in the nervous system. Netrin-1, an axonal guidance cue, can also promote axonal guidance growth, but the molecular mechanism of axonal guidance growth under indirect electric stimulation is still unknown. We investigated the molecular mechanism of axonal guidance growth under piezoelectric ceramic lead zirconate titanate (PZT) stimulation in the primary cultured cortical neurons. PZT induced marked axonal elongation. Moreover, PZT activated the excitatory postsynaptic currents (EPSCs) by increasing the frequency and amplitude of EPSCs of the cortical neurons in patch clamp assay. PZT downregulated the expression of Netrin-1 and its receptor Deleted in Colorectal Cancer (DCC). Rho GTPase signaling is involved in interactions of Netrin-1 and DCC. PZT activated RhoA. Dramatic decrease of Cdc42 and Rac1 was also observed after PZT treatment. RhoA inhibitor Clostridium botulinum C3 exoenzyme (C3-Exo) prevented the PZT-induced downregulation of Netrin-1 and DCC. We suggest that PZT can promote axonal guidance growth by downregulation of Netrin-1 and DCC to mediate axonal repulsive responses via the Rho GTPase signaling pathway. Obviously, piezoelectric materials may provide a new approach for axonal recovery and be beneficial for clinical therapy in the future.

  14. SU-F-T-675: Down-Regulating the Expression of Cdc42 and Inhibition of Migration of A549 with Combined Treatment of Ionizing Radiation and Sevoflurane

    International Nuclear Information System (INIS)

    Feng, Y; Feng, J; Huang, Z

    2016-01-01

    Purpose: Cdc42 is involved in cell transformation, proliferation, invasion and metastasis of human cancer cells. Cdc42 overexpression has been reported in several types of cancers. This study investigated the combined treatment effects of ionizing radiation and sevoflurane on down-regulating Cdc42 expression and suppressing migration of human adenocarcinoma cell line A549. Methods: Samples of A549 cells with Cdc42 overexpression were created and Cdc42 expression was determined by Western blotting. Increase of migration speed by Cdc42-HA overexpression was confirmed with an initial in-vitro scratch assay. The cells grown in culture media were separated into 2 groups of 6 samples: one for the control and the other was treated with 4% sevoflurane for 5hrs prior to a single-fraction radiation of 4Gy using a 6MV beam. Cell migration speeds of the 2 groups were measured with an initial in-vitro scratch assay. The scratch was created with a pipette tip immediately after treatment and images at 4 post-treatment time points (0h, 3h, 6h, 12h) were acquired. The distance between the two separated sides at 0h was used as reference and subsequent changes of the distance over time was defined as the cell migration speed. Image processing and measurement were performed with an in-house software. The experiment was repeated three times independently to evaluate the repeatability and reliability. Statistical analysis was performed with SPSS 19.0. Results: Western blotting showed the treatment down-regulated Cdc42 overexpression. Quantitative analysis and two-tailed t-test showed that cell migration speed of the treated group was higher than the control group at all time points after treatment (p < 0.02). Conclusion: Combined treatment of 6MV photon and sevoflurane can cause the effects of down-regulating Cdc42 overexpression and decrease of migration speed of A549 cells which provides potential of clinical benefit for the cancer therapy. More investigation is needed to further

  15. SU-F-T-675: Down-Regulating the Expression of Cdc42 and Inhibition of Migration of A549 with Combined Treatment of Ionizing Radiation and Sevoflurane

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Y [East Carolina University, Greenville, NC (United States); Feng, J [Tianjin University, Tianjin (China); Huang, Z [East Carolina University, Greenville, NC (United States)

    2016-06-15

    Purpose: Cdc42 is involved in cell transformation, proliferation, invasion and metastasis of human cancer cells. Cdc42 overexpression has been reported in several types of cancers. This study investigated the combined treatment effects of ionizing radiation and sevoflurane on down-regulating Cdc42 expression and suppressing migration of human adenocarcinoma cell line A549. Methods: Samples of A549 cells with Cdc42 overexpression were created and Cdc42 expression was determined by Western blotting. Increase of migration speed by Cdc42-HA overexpression was confirmed with an initial in-vitro scratch assay. The cells grown in culture media were separated into 2 groups of 6 samples: one for the control and the other was treated with 4% sevoflurane for 5hrs prior to a single-fraction radiation of 4Gy using a 6MV beam. Cell migration speeds of the 2 groups were measured with an initial in-vitro scratch assay. The scratch was created with a pipette tip immediately after treatment and images at 4 post-treatment time points (0h, 3h, 6h, 12h) were acquired. The distance between the two separated sides at 0h was used as reference and subsequent changes of the distance over time was defined as the cell migration speed. Image processing and measurement were performed with an in-house software. The experiment was repeated three times independently to evaluate the repeatability and reliability. Statistical analysis was performed with SPSS 19.0. Results: Western blotting showed the treatment down-regulated Cdc42 overexpression. Quantitative analysis and two-tailed t-test showed that cell migration speed of the treated group was higher than the control group at all time points after treatment (p < 0.02). Conclusion: Combined treatment of 6MV photon and sevoflurane can cause the effects of down-regulating Cdc42 overexpression and decrease of migration speed of A549 cells which provides potential of clinical benefit for the cancer therapy. More investigation is needed to further

  16. START-GAP3/DLC3 is a GAP for RhoA and Cdc42 and is localized in focal adhesions regulating cell morphology

    International Nuclear Information System (INIS)

    Kawai, Katsuhisa; Kiyota, Minoru; Seike, Junichi; Deki, Yuko; Yagisawa, Hitoshi

    2007-01-01

    In the human genome there are three genes encoding RhoGAPs that contain the START (steroidogenic acute regulatory protein (StAR)-related lipid transfer)-domain. START-GAP3/DLC3 is a tumor suppressor gene similar to two other human START-GAPs known as DLC1 or DLC2. Although expression of START-GAP3/DLC3 inhibits the proliferation of cancer cells, its molecular function is not well understood. In this study we carried out biochemical characterization of START-GAP3/DLC3, and explored the effects of its expression on cell morphology and intracellular localization. We found that START-GAP3/DLC3 serves as a stimulator of PLCδ1 and as a GAP for both RhoA and Cdc42 in vitro. Moreover, we found that the GAP activity is responsible for morphological changes. The intracellular localization of endogenous START-GAP3/DLC3 was explored by immunocytochemistry and was revealed in focal adhesions. These results indicate that START-GAP3/DLC3 has characteristics similar to other START-GAPs and the START-GAP family seems to share common characteristics

  17. Cdc42 and Rab8a are critical for intestinal stem cell division, survival, and differentiation in mice

    DEFF Research Database (Denmark)

    Sakamori, Ryotaro; Das, Soumyashree; Yu, Shiyan

    2012-01-01

    The constant self renewal and differentiation of adult intestinal stem cells maintains a functional intestinal mucosa for a lifetime. However, the molecular mechanisms that regulate intestinal stem cell division and epithelial homeostasis are largely undefined. We report here that the small GTPases...... reminiscent of human microvillus inclusion disease (MVID), a devastating congenital intestinal disorder that results in severe nutrient deprivation. Further analysis revealed that Cdc42-deficient stem cells had cell division defects, reduced capacity for clonal expansion and differentiation into Paneth cells...... suggest that defects of the stem cell niche can cause MVID. This hypothesis represents a conceptual departure from the conventional view of this disease, which has focused on the affected enterocytes, and suggests stem cell-based approaches could be beneficial to infants with this often lethal condition....

  18. Cdc42 and Rac1 signaling are both required for and act synergistically in the correct formation of myelin sheaths in the CNS

    DEFF Research Database (Denmark)

    Thurnherr, Tina; Benninger, Yves; Wu, Xunwei

    2006-01-01

    . This was characterized by the extraordinary enlargement of the inner tongue of the oligodendrocyte process and concomitant formation of a myelin outfolding as a result of abnormal accumulation of cytoplasm in this region. Ablation of Rac1 also resulted in the abnormal accumulation of cytoplasm in the inner tongue...... of the oligodendrocyte process, and we provide genetic evidence that rac1 synergizes with cdc42 in a gene dosage-dependent way to regulate myelination....

  19. RhoA, Rac1 and Cdc42 differentially regulate aSMA and collagen I expression in mesenchymal stem cells.

    Science.gov (United States)

    Ge, Jianfeng; Burnier, Laurent; Adamopoulou, Maria; Kwa, Mei Qi; Schaks, Matthias; Rottner, Klemens; Brakebusch, Cord

    2018-04-26

    Mesenchymal stem cells (MSC) are suggested to be important progenitors of myofibroblasts in fibrosis. To understand the role of Rho GTPase signaling in TGFβ-induced myofibroblast differentiation of MSC, we generated a novel MSC line and descendants of it lacking functional Rho GTPases and Rho GTPase signaling components. Unexpectedly, our data revealed that Rho GTPase signaling is required for TGFβ-induced expression of αSMA, but not of collagen I α1 (col1a1). While loss of RhoA and Cdc42 reduced αSMA expression, ablation of the Rac1 gene had the opposite effect. Although actin polymerization and MRTFa were crucial for TGFβ-induced αSMA expression, neither Arp2/3 dependent actin polymerization nor cofilin dependent severing and depolymerization of F-actin were required. Instead, F-actin levels were dependent on cell contraction and TGFβ-induced actin polymerisation correlated with increased cell contraction mediated by RhoA and Cdc42. Finally, we observed impaired collagen I secretion in MSC lacking RhoA or Cdc42. These data give novel molecular insights into the role of Rho GTPases in TGFβ signaling and have implications for our understanding of MSC function in fibrosis. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Plasma levels of intact and cleaved urokinase plasminogen activator receptor (uPAR) in men with clinically localised prostate cancer

    DEFF Research Database (Denmark)

    Kristensen, Gitte; Berg, Kasper Drimer; Lippert, Solvej

    2017-01-01

    Aims: Lymph node metastasis (N1) is an adverse prognostic factor for men with clinically localised prostate cancer (PCa), but the prediction of N1 disease remains difficult. Urokinase plasminogen activator receptor (uPAR) plays an important role in angiogenesis and tumorigenesis. We analysed...... analysis and quantified using the areas under the ROC curve (AUC).Results: All soluble uPAR levels were significantly (p=0.03) higher in patients with N1 disease compared with patients with N0/x disease. ROC curves including clinical tumour stage, biopsy Gleason score, prostate-specific antigen and percent...

  1. In normal human fibroblasts variation in DSB repair capacity cannot be ascribed to radiation-induced changes in the localisation, expression or activity of major NHEJ proteins

    DEFF Research Database (Denmark)

    Kasten-Pisula, Ulla; Vronskaja, Svetlana; Overgaard, Jens

    2008-01-01

    in the activity of the DNA-PK complex induced upon irradiation. CONCLUSIONS: For normal human fibroblasts, the level or activity of NHEJ proteins measured prior to or after irradiation cannot be used to predict the DSB repair capacity or cellular radiosensitivity. Udgivelsesdato: 2008-Mar......BACKGROUND AND PURPOSE: The aim of the present study was to test whether for normal human fibroblasts the variation in double-strand break (DSB) repair capacity results from radiation-induced differences in localisation, expression or activity of major non-homologous end-joining (NHEJ) proteins....... MATERIALS AND METHODS: Experiments were performed with 11 normal human fibroblast strains AF01-11. NHEJ proteins were determined by Western blot and DNA-PK activity by pulldown-assay. RESULTS: The four NHEJ proteins tested (Ku70, Ku80, XRCC4 and DNA-PKcs) were found to be localised almost exclusively...

  2. Automatic reference selection for quantitative EEG interpretation: identification of diffuse/localised activity and the active earlobe reference, iterative detection of the distribution of EEG rhythms.

    Science.gov (United States)

    Wang, Bei; Wang, Xingyu; Ikeda, Akio; Nagamine, Takashi; Shibasaki, Hiroshi; Nakamura, Masatoshi

    2014-01-01

    EEG (Electroencephalograph) interpretation is important for the diagnosis of neurological disorders. The proper adjustment of the montage can highlight the EEG rhythm of interest and avoid false interpretation. The aim of this study was to develop an automatic reference selection method to identify a suitable reference. The results may contribute to the accurate inspection of the distribution of EEG rhythms for quantitative EEG interpretation. The method includes two pre-judgements and one iterative detection module. The diffuse case is initially identified by pre-judgement 1 when intermittent rhythmic waveforms occur over large areas along the scalp. The earlobe reference or averaged reference is adopted for the diffuse case due to the effect of the earlobe reference depending on pre-judgement 2. An iterative detection algorithm is developed for the localised case when the signal is distributed in a small area of the brain. The suitable averaged reference is finally determined based on the detected focal and distributed electrodes. The presented technique was applied to the pathological EEG recordings of nine patients. One example of the diffuse case is introduced by illustrating the results of the pre-judgements. The diffusely intermittent rhythmic slow wave is identified. The effect of active earlobe reference is analysed. Two examples of the localised case are presented, indicating the results of the iterative detection module. The focal and distributed electrodes are detected automatically during the repeating algorithm. The identification of diffuse and localised activity was satisfactory compared with the visual inspection. The EEG rhythm of interest can be highlighted using a suitable selected reference. The implementation of an automatic reference selection method is helpful to detect the distribution of an EEG rhythm, which can improve the accuracy of EEG interpretation during both visual inspection and automatic interpretation. Copyright © 2013 IPEM

  3. Two closely related Rho GTPases, Cdc42 and RacA, of the en-dophytic fungus Epichloë festucae have contrasting roles for ROS production and symbiotic infection synchronized with the host plant.

    Science.gov (United States)

    Kayano, Yuka; Tanaka, Aiko; Takemoto, Daigo

    2018-01-01

    Epichloë festucae is an endophytic fungus which systemically colonizes temperate grasses to establish symbiotic associations. Maintaining symptomless infection is a key requirement for endophytes, a feature that distinguishes them from pathogenic fungi. While pathogenic fungi extend their hyphae by tip growth, hyphae of E. festucae systemically colonize the intercellular space of expanding host leaves via a unique mechanism of hyphal intercalary growth. This study reports that two homologous Rho GTPases, Cdc42 and RacA, have distinctive roles in the regulation of E. festucae growth in planta. Here we highlight the vital role of Cdc42 for intercalary hyphal growth, as well as involvement of RacA in regulation of hyphal network formation, and demonstrate the consequences of mutations in these genes on plant tissue infection. Functions of Cdc42 and RacA are mediated via interactions with BemA and NoxR respectively, which are expected components of the ROS producing NOX complex. Symbiotic defects found in the racA mutant were rescued by introduction of a Cdc42 with key amino acids substitutions crucial for RacA function, highlighting the significance of the specific interactions of these GTPases with BemA and NoxR for their functional differentiation in symbiotic infection.

  4. Development of a new technique of localised analysis of electrically active defects in semiconductors

    International Nuclear Information System (INIS)

    Heiser, T.

    1988-07-01

    An analysis technique derived from minority carrier transient spectroscopy (MCTS) was developed. By giving this technique spatial resolution via a focused optical beam, it is possible to exploit the high sensitivity and the spectroscopic nature of the technique to develop a method called scanning MCTS (SMCTS) which can be used to acquire information on lateral distribution of electrically active flaws in semiconductors or associated chemical impurities. The optimum conditions, corresponding to the maximum signal for the highest resolution, can be expressed by the value of a signal parameter. The transients system was digitized, considerably reducing background noise. In order to link the SMCTS to a given flaw, two methods for exploiting the transients are used. The method was verified in tests with artificial defects created by laser and on real cases, arising in industrial processes [fr

  5. Expression and Immunohistochemical Localisation of the G beta gamma activated and Calcineurin-inhibited Adenylyl Cyclase Isoforms in Rat Articular Chondrocytes

    International Nuclear Information System (INIS)

    Memon, I.; Khan, K.M.; Siddiqui, S.; Perveen, S.; Ishaq, M.

    2016-01-01

    Objective: To determine the expression and localisation of the Gβγ-activated adenylyl cyclase (AC) isoforms 2, 4, and 7 and calcineurin-inhibited AC isoform 9 in rat articular chondrocytes. Study Design: Experimental study. Place and Duration of Study: Jumma Research Laboratory and Histology Laboratory, The Aga Khan University, Karachi, from 2009 to 2011. Methodology: Fresh slices of articular cartilage were taken from various synovial joints of rats of different age groups. The expression of AC isoforms was determined by RT-PCR and immunohistochemistry was performed to localise these isoforms in articular chondrocytes. Tissue sections were processed for immunostaining with respective antibodies. The color was developed by diaminobenzidine. Results: All the studied AC isoforms were found to be differentially expressed in different zones of the rat articular cartilage. Generally, expression of all AC isoforms studied increased with age. The expression of the AC isoforms through PCR was almost consistent with the localisation of these isoforms by immunohistochemistry. Conclusion: These data add to the information about signalling cascades possibly involved in articular chondrocytes. Variable expression of AC isoforms 2, 4, 7, and 9 suggest a role for the signalling cascades regulated by the AC isoforms in articular chondrocytes. (author)

  6. Localisation for industrial development

    CSIR Research Space (South Africa)

    Bhugwandin, Ashley

    2017-10-01

    Full Text Available This presentation focuses on localisation for industrial development, and is presented by Ashley Bhugwandin at The 6th CSIR Conference: Ideas that work for industrial development, 5-6 October 2017, CSIR International Convention Centre, Pretoria...

  7. Molecular cloning of the gene for the human placental GTP-binding protein Gp (G25K): Identification of this GTP-binding protein as the human homolog of the yeast cell-division-cycle protein CDC42

    International Nuclear Information System (INIS)

    Shinjo, K.; Koland, J.G.; Hart, M.J.; Narasimhan, V.; Cerione, R.A.; Johnson, D.I.; Evans, T.

    1990-01-01

    The authors have isolated cDNA clones from a human placental library that code for a low molecular weight GTP-binding protein originally designated G p (also called G25K). This identification is based on comparisons with the available peptide sequences for the purified human G p protein and the use of two highly specific anti-peptide antibodies. The predicted amino acid sequence of the protein is very similar to those of various members of the ras superfamily of low molecular weight GTP-binding proteins, including the N-, Ki-, and Ha-ras proteins (30-35% identical), the rho proteins and the rac proteins. The highest degree of sequence identity (80%) is found with the Saccharomyces cerevisiae cell division-cycle protein CDC42. The human placental gene, which they designate CDC42Hs, complements the cdc42-1 mutation in S. cerevisiae, which suggests that this GTP-binding protein is the human homolog of the yeast protein

  8. Design of a randomised controlled trial of adapted physical activity during adjuvant treatment for localised breast cancer: the PASAPAS feasibility study

    Science.gov (United States)

    Touillaud, M; Foucaut, A-M; Berthouze, S E; Reynes, E; Kempf-Lépine, A-S; Carretier, J; Pérol, D; Guillemaut, S; Chabaud, S; Bourne-Branchu, V; Perrier, L; Trédan, O; Fervers, B; Bachmann, P

    2013-01-01

    Introduction After a diagnosis of localised breast cancer, overweight, obesity and weight gain are negatively associated with prognosis. In contrast, maintaining an optimal weight through a balanced diet combined with regular physical activity appears to be effective protective behaviour against comorbidity or mortality after a breast cancer diagnosis. The primary aim of the Programme pour une Alimentation Saine et une Activité Physique Adaptée pour les patientes atteintes d'un cancer du Sein (PASAPAS) randomised controlled trial is to evaluate the feasibility of implementing an intervention of adapted physical activity (APA) for 6 months concomitant with the prescription of a first line of adjuvant chemotherapy. Secondary aims include assessing the acceptability of the intervention, compliance to the programme, process implementation, patients’ satisfaction, evolution of biological parameters and the medicoeconomic impact of the intervention. Methods and analysis The study population consists of 60 women eligible for adjuvant chemotherapy after a diagnosis of localised invasive breast cancer. They will be recruited during a 2-year inclusion period and randomly allocated between an APA intervention arm and a control arm following a 2:1 ratio. All participants should benefit from personalised dietetic counselling and patients allocated to the intervention arm will be offered an APA programme of two to three weekly sessions of Nordic walking and aerobic fitness. During the 6-month intervention and 6-month follow-up, four assessments will be performed including blood draw, anthropometrics and body composition measurements, and questionnaires about physical activity level, diet, lifestyle factors, psychological criteria, satisfaction with the intervention and medical data. Ethics and dissemination The study was approved by the French Ethics Committee (Comité de Protection des Personnes Sud-Est IV) and the national agencies for biomedical studies and for privacy

  9. The brain smell centres - comparison of localisation and activation in male and female subjects using functional MR imaging

    International Nuclear Information System (INIS)

    Marchwicka-Wasiak, M.; Goraj, B.

    2004-01-01

    The study was conducted in order to determine and to compare the location and activation of smell brain centres in females and males brains using olfactory nerve-mediated (geraniol) and combined olfactory and trigeminal nerve-mediated (patchouli) stimulants. 10 normal volunteers (five women and five men), right-handed, non-smokers, without any CNS diseases were examined to determine the activated cortex areas during stimulation by geraniol and patchouli. MR brain scans were obtained using a 1.5 T clinical scanner, with the head-neck coil. The imaging was performed in each subject using SE and EPI sequences with a blood-oxygen-level-dependent (BOLD) effect. The individual inhaled odorized air during the 30 seconds period and alternating room air over the same period. The mean pixel intensity of activated images was substracted from the mean pixel intensity of preactivated images. The olfactory system-mediated stimuli (geraniol) evoked bilateral activation of female brains smell centres and right hemisphere centres activation in male brains. The exposure to the olfactory and trigeminal nerve-mediated stimuli (patchouli) showed more activated regions in both sexes than to the olfactory nerve-ediated stimuli. fMRI proved to be a useful method to compare the location and activation of male and female brain smell centres. (author)

  10. Localisation of the subthalamic nucleus in Parkinson's disease with neural beta and gamma activity of local field potentials

    NARCIS (Netherlands)

    Verhagen, R.; Zwartjes - de Klerk, D.G.M; Heida, Tjitske; Contarino, M.F.; de Bie, R.M.A.; van den Munckhof, P; Schuurman, P.R.; Martens, H.C.F.; Veltink, Petrus H.; Bour, L.J.

    2013-01-01

    To evaluate the nature of oscillatory activity in the subthalamic nucleus (STN) by means of intraoperative local field potential (LFP) recordings, its relationship with microelectrode recordings (MER) and its potential use to locate the STN and its sensorimotor sub-area in patients with Parkinson’s

  11. Small and intermediate conductance Ca(2+)-activated K+ channels confer distinctive patterns of distribution in human tissues and differential cellular localisation in the colon and corpus cavernosum.

    Science.gov (United States)

    Chen, Mao Xiang; Gorman, Shelby A; Benson, Bill; Singh, Kuljit; Hieble, J Paul; Michel, Martin C; Tate, Simon N; Trezise, Derek J

    2004-06-01

    The SK/IK family of small and intermediate conductance calcium-activated potassium channels contains four members, SK1, SK2, SK3 and IK1, and is important for the regulation of a variety of neuronal and non-neuronal functions. In this study we have analysed the distribution of these channels in human tissues and their cellular localisation in samples of colon and corpus cavernosum. SK1 mRNA was detected almost exclusively in neuronal tissues. SK2 mRNA distribution was restricted but more widespread than SK1, and was detected in adrenal gland, brain, prostate, bladder, liver and heart. SK3 mRNA was detected in almost every tissue examined. It was highly expressed in brain and in smooth muscle-rich tissues including the clitoris and the corpus cavernosum, and expression in the corpus cavernosum was upregulated up to 5-fold in patients undergoing sex-change operations. IK1 mRNA was present in surface-rich, secretory and inflammatory cell-rich tissues, highest in the trachea, prostate, placenta and salivary glands. In detailed immunohistochemical studies of the colon and the corpus cavernosum, SK1-like immunoreactivity was observed in the enteric neurons. SK3-like immunoreactivity was observed strongly in smooth muscle and vascular endothelium. IK1-like immunoreactivity was mainly observed in inflammatory cells and enteric neurons of the colon, but absent in corpus cavernosum. These distinctive patterns of distribution suggest that these channels are likely to have different biological functions and could be specifically targeted for a number of human diseases, such as irritable bowel syndrome, hypertension and erectile dysfunction.

  12. Strain localisation in granular media

    OpenAIRE

    Desrues , Jacques

    1984-01-01

    This study is devoted to strain localisation in Granular materials. Both experimental and theoretical results have been obtained.The first part of the thesis is a review of the methods and theories about rupture in sols mechanics and more generally, in solid mechanics. The classical framework of Shear Band analysis is presented, and the main results available for different classes of materials are discussed.The second part describes an experimental study of strain localisation in sand specime...

  13. A Localised Corrosion Cell for Industrial Applications

    DEFF Research Database (Denmark)

    Andersen, A.; Hilbert, Lisbeth Rischel; Jansen, P.

    2003-01-01

    The LOCORR-CELL™ developed by FORCE TECHNOLOGY is an electrochemical cell for industrial applications estimating localised corrosion. The cell is constructed in a carbon steel casing for direct mounting into the system. It is based on an oxygen concentration element reflecting the interaction...... between the environment formed under a deposit or in a crevice. The essential feature of the method is that it reflects the influence of oxygen content, conductivity and temperature as well as the influence of corrosion inhibitors, MIC and other effects that have an effect on localised corrosion under...... deposits and in crevices. The measuring principle in the cell is based on measurements of the galvanic current flow between the steel anode covered by a porous glass frit and the surrounding steel casing. The current is measured by a zero-resistance circuit-instrument and the activity can be presented...

  14. Problems associated with localised skin exposures

    International Nuclear Information System (INIS)

    Wells, J.

    1986-01-01

    The possible sources of localised skin exposure include small commercial sources (for radiotherapy, for example), radiopharmaceuticals, collimated microbeams, and both fission and activation products from nuclear reactors, neutron generators and associated facilities. Each of these sources has its own particular characteristics and associated problems. Recommendations and regulations relating to limits on skin dose for such exposures have been constrained by inadequate radiobiological data and the limitations inherent in personal dosimetric techniques. A growing body of data is now available for beta-emitters which allows a preliminary reassessment of some aspects of the currently recommended dose limits for localised skin exposures. How the skin dose is measured is particularly important for such exposures, as doses often have to be averaged over a specific area. The area chosen for dose measurement and the depth at which the measurement is made are crucial to understanding the possible biological consequences and for formulating appropriate protection criteria. (author)

  15. Novel derivative of Paeonol, Paeononlsilatie sodium, alleviates behavioral damage and hippocampal dendritic injury in Alzheimer's disease concurrent with cofilin1/phosphorylated-cofilin1 and RAC1/CDC42 alterations in rats.

    Directory of Open Access Journals (Sweden)

    Fei Han

    Full Text Available Alzheimer's disease (AD is a typical hippocampal amnesia and the most common senile dementia. Many studies suggest that cognitive impairments are more closely correlated with synaptic loss than the burden of amyloid deposits in AD progression. To date, there is no effective treatment for this disease. Paeonol has been widely employed in traditional Chinese medicine. This compound improves learning behavior in an animal model; however, the mechanism remains unclear. In this study, Paeononlsilatie sodium (Pa, a derivative of Paeonol, attenuated D-galactose (D-gal and AlCl3-induced behavioral damages in rats based on evaluations of the open field test (OFT, elevated plus maze test (EPMT, and Morris water maze test (MWMT. Pa increased the dendritic complexity and the density of dendritic spines. Correlation analysis indicated that morphological changes in neuronal dendrites are closely correlated with behavioral changes. Pa treatment reduced the production of Aβ, affected the phosphorylation and redistribution of cofilin1 and inhibited rod-like formation in hippocampal neurons. The induction of D-gal and AlCl3 promoted the expression of RAC1/CDC42 expression; however, the tendency of gene expression was inhibited by pretreatment with Pa. Taken together, our results suggest that Pa may represent a novel therapeutic agent for the improvement of cognitive and emotional behaviors and dendritic morphology in an AD animal model.

  16. Rare localisations of osteochondrosis juvenilis

    Energy Technology Data Exchange (ETDEWEB)

    Schumacher, R; Schuster, W; Mueller, U

    1981-04-01

    A survey of rare localisations of osteochondrosis juvenilis is given and illustrated by cases of Morbus Friedrich, Morbus Panner, Vertebra plana Calve, Morbus Blount, Morbus Iselin, Morbus Hegemann and Morbus Thiemann. This is followed by discussion of etiology and differential diagnosis.

  17. Disruption of the Cdc42/Par6/aPKC or Dlg/Scrib/Lgl Polarity Complex Promotes Epithelial Proliferation via Overlapping Mechanisms.

    Science.gov (United States)

    Schimizzi, Gregory V; Maher, Meghan T; Loza, Andrew J; Longmore, Gregory D

    2016-01-01

    The establishment and maintenance of apical-basal polarity is a defining characteristic and essential feature of functioning epithelia. Apical-basal polarity (ABP) proteins are also tumor suppressors that are targeted for disruption by oncogenic viruses and are commonly mutated in human carcinomas. Disruption of these ABP proteins is an early event in cancer development that results in increased proliferation and epithelial disorganization through means not fully characterized. Using the proliferating Drosophila melanogaster wing disc epithelium, we demonstrate that disruption of the junctional vs. basal polarity complexes results in increased epithelial proliferation via distinct downstream signaling pathways. Disruption of the basal polarity complex results in JNK-dependent proliferation, while disruption of the junctional complex primarily results in p38-dependent proliferation. Surprisingly, the Rho-Rok-Myosin contractility apparatus appears to play opposite roles in the regulation of the proliferative phenotype based on which polarity complex is disrupted. In contrast, non-autonomous Tumor Necrosis Factor (TNF) signaling appears to suppress the proliferation that results from apical-basal polarity disruption, regardless of which complex is disrupted. Finally we demonstrate that disruption of the junctional polarity complex activates JNK via the Rho-Rok-Myosin contractility apparatus independent of the cortical actin regulator, Moesin.

  18. Periostitis and localised myositis in polyarteritis nodosa

    International Nuclear Information System (INIS)

    Macdonald, W.B.G.; Blake, M.P.

    2003-01-01

    Full text: A 20-year-old man with previously diagnosed polyarteritis nodosa was referred for a bone scan to investigate longstanding knee and lower leg pain. The patient's symptoms worsened with any reduction of steroid dose and his physician was concerned about avascular necrosis of the hips. Plain x-rays of the lower limbs were normal. The blood pool images showed bilaterally increased activity in the anterior muscle compartments of the lower legs, suggestive of localised myositis. Three-hour delayed images showed widespread, increased subperiosteal activity with no evidence of avascular necrosis. Subsequent MRI scanning showed patchy muscle enhancement in both lower legs, also typical of myositis. A muscle biopsy was performed which demonstrated features of both myositis and vasculitis. The patient remains dependent on high-dose steroids for symptom relief. Localised myositis has previously been reported in polyarteritis nodosa and is a recognised, albeit rare, complication of the disorder, the basis of which is not well understood. Diagnostic muscle biopsy should be directed at involved muscle groups, which are best detected with MRI. Lower limb periostitis is well described in polyarteritis nodosa and may result in gross deformity. Several cases have previously been reported in the literature based on radiographic abnormalities, which were not present in our patient. Bone scanning demonstrated the sub-periosteal activity well in our subject and is suggested as a useful investigation in patients with polyarteritis nodosa who complain of lower limb pain. Copyright (2003) The Australian and New Zealand Society of Nuclear Medicine Inc

  19. Localisation of RNAs into the germ plasm of vitellogenic Xenopus oocytes.

    Directory of Open Access Journals (Sweden)

    Sarbjit Nijjar

    Full Text Available We have studied the localisation of mRNAs in full-grown Xenopus laevis oocytes by injecting fluorescent RNAs, followed by confocal microscopy of the oocyte cortex. Concentrating on RNA encoding the Xenopus Nanos homologue, nanos1 (formerly Xcat2, we find that it consistently localised into aggregated germ plasm ribonucleoprotein (RNP particles, independently of cytoskeletal integrity. This implies that a diffusion/entrapment-mediated mechanism is active, as previously reported for previtellogenic oocytes. Sometimes this was accompanied by localisation into scattered particles of the "late", Vg1/VegT pathway; occasionally only late pathway localisation was seen. The Xpat RNA behaved in an identical fashion and for neither RNA was the localisation changed by any culture conditions tested. The identity of the labelled RNP aggregates as definitive germ plasm was confirmed by their inclusion of abundant mitochondria and co-localisation with the germ plasm protein Hermes. Further, the nanos1/Hermes RNP particles are interspersed with those containing the germ plasm protein Xpat. These aggregates may be followed into the germ plasm of unfertilized eggs, but with a notable reduction in its quantity, both in terms of injected molecules and endogenous structures. Our results conflict with previous reports that there is no RNA localisation in large oocytes, and that during mid-oogenesis even germ plasm RNAs localise exclusively by the late pathway. We find that in mid oogenesis nanos1 RNA also localises to germ plasm but also by the late pathway. Late pathway RNAs, Vg1 and VegT, also may localise into germ plasm. Our results support the view that mechanistically the two modes of localisation are extremely similar, and that in an injection experiment RNAs might utilise either pathway, the distinction in fates being very subtle and subject to variation. We discuss these results in relation to their biological significance and the results of others.

  20. Reaction-Diffusion Automata Phenomenology, Localisations, Computation

    CERN Document Server

    Adamatzky, Andrew

    2013-01-01

    Reaction-diffusion and excitable media are amongst most intriguing substrates. Despite apparent simplicity of the physical processes involved the media exhibit a wide range of amazing patterns: from target and spiral waves to travelling localisations and stationary breathing patterns. These media are at the heart of most natural processes, including morphogenesis of living beings, geological formations, nervous and muscular activity, and socio-economic developments.   This book explores a minimalist paradigm of studying reaction-diffusion and excitable media using locally-connected networks of finite-state machines: cellular automata and automata on proximity graphs. Cellular automata are marvellous objects per se because they show us how to generate and manage complexity using very simple rules of dynamical transitions. When combined with the reaction-diffusion paradigm the cellular automata become an essential user-friendly tool for modelling natural systems and designing future and emergent computing arch...

  1. Multimodal Localisation: Analysis, Algorithms and Experimental Evaluation

    NARCIS (Netherlands)

    Kavitha Muthukrishnan, K.

    2009-01-01

    The term localisation is derived from the word locale, which traditionally means a small area or vicinity. In ancient days, localisation meant navigation -- an art of finding the way from one place to another. Tremendous advancement in the science of navigation dates back to the sixteenth century,

  2. Quantum localisation on the circle

    Science.gov (United States)

    Fresneda, Rodrigo; Gazeau, Jean Pierre; Noguera, Diego

    2018-05-01

    Covariant integral quantisation using coherent states for semi-direct product groups is implemented for the motion of a particle on the circle. In this case, the phase space is the cylinder, which is viewed as a left coset of the Euclidean group E(2). Coherent states issued from fiducial vectors are labeled by points in the cylinder and depend also on extra parameters. We carry out the corresponding quantisations of the basic classical observables, particularly the angular momentum and the 2π-periodic discontinuous angle function. We compute their corresponding lower symbols. The quantum localisation on the circle is examined through the properties of the angle operator yielded by our procedure, its spectrum and lower symbol, its commutator with the quantum angular momentum, and the resulting Heisenberg inequality. Comparison with other approaches to the long-standing question of the quantum angle is discussed.

  3. Radioactive probes for human gene localisation by in situ hybridisation

    International Nuclear Information System (INIS)

    Fennell, S.J.

    1980-07-01

    Radioactive probes of high specific activity have been used for human gene localisation on metaphase chromosome preparations. Human 5S ribosomal RNA was used as a model system, as a probe for the localisation of human 5S ribosomal genes. 125 I-labelled mouse 5S ribosomal RNA was used to study the 5S ribosomal gene content and arrangement in families with translocations on the long arm of chromosome 1 close to or containing the 5S ribosomal RNA locus, by in situ hybridisation to human metaphase chromosomes from peripheral blood cultures. This confirmed the chromosomal assignment of 5S ribosomal genes to 1q 42-43. In situ hybridisation probes were also prepared from recombinant plasmids containing Xenopus laevis oocyte 5S or 28S/18S gene sequences to give [ 3 H]-labelled cRNA and [ 3 H]-labelled nick-translated plasmid DNA. Studies on the kinetics of hybridisation of plasmid probes with and without ribosomal gene sequences questioned the role of plasmid DNA for amplification of signal during gene localisation. Gene localisation was obtained with nick-translated plasmid DNA containing the 28S/18S ribosomal DNA insert after short exposure times, but poor results were obtained using a [ 3 H]-labelled cRNA probe transcribed from the plasmid with the 5S gene insert. (author)

  4. Sprouty regulates cell migration by inhibiting the activation of Rac1 GTPase

    International Nuclear Information System (INIS)

    Poppleton, Helen M.; Edwin, Francis; Jaggar, Laura; Ray, Ramesh; Johnson, Leonard R.; Patel, Tarun B.

    2004-01-01

    Sprouty (SPRY) protein negatively modulates fibroblast growth factor and epidermal growth factor actions. We showed that human SPRY2 inhibits cell growth and migration in response to serum and several growth factors. Using rat intestinal epithelial (IEC-6) cells, we investigated the involvement of the Rho family of GTPases, RhoA, Rac1, and cdc42 in SPRY2-mediated inhibition of cell migration and proliferation. The ability of TAT-tagged SPRY2 to inhibit proliferation and migration of IEC-6 cells transfected with constitutively active mutants of RhoA(G14V), Rac1(G12V), and cdc42 (F28L) was determined. Constitutively active RhoA(G14V), Rac1(G12V), or cdc42(F28L) did not protect cells from the anti-proliferative actions of TAT-SPRY2. The ability of TAT-hSPRY2 to inhibit migration was not altered by of RhoA(G14V) and cdc42(F28L). However, Rac1(G12V) obliterated the ability of SPRY2 to inhibit cell autonomous or serum-induced migration. Also, the activation of endogenous Rac1 was attenuated by TAT-SPRY2. Thus, SPRY2 mediates its anti-migratory actions by inhibiting Rac1 activation

  5. Experiences with a new breast localisation needle

    International Nuclear Information System (INIS)

    Hergan, K.; Amann, T.; Doringer, W.; Hollenstein, P.

    1990-01-01

    In view of the increasing number of biopsies of non-palpable lesions of the female breast we found an ideal localisation system in the Hawkins breast localisation needle. Localisation was successful without technical problems in 31 out of 34 patients. The special advantages of the needle are its stability in position and excellent manoeverability due to the construction of the needle. The very simple handling of the needle is an advantage not only for the radiologist but also for the surgeon. (orig.) [de

  6. Implementing localisation programmes in South Africa

    CSIR Research Space (South Africa)

    Strachan, Garth

    2017-10-01

    Full Text Available challenges – from job creation and poverty reduction to participating in the technological revolution and global value chains, from promoting efficient and clean energy to mitigating climate change and greening the economy – without using some kind... sector value chains where the public sector supports supplier development – e.g. automotives, retail, clothing and textiles etc. Support for technology localisation and diffusion – The Technology Localisation and Implementation Unit [TLIU...

  7. Mutant RBL mast cells defective in Fc epsilon RI signaling and lipid raft biosynthesis are reconstituted by activated Rho-family GTPases.

    Science.gov (United States)

    Field, K A; Apgar, J R; Hong-Geller, E; Siraganian, R P; Baird, B; Holowka, D

    2000-10-01

    Characterization of defects in a variant subline of RBL mast cells has revealed a biochemical event proximal to IgE receptor (Fc epsilon RI)-stimulated tyrosine phosphorylation that is required for multiple functional responses. This cell line, designated B6A4C1, is deficient in both Fc epsilon RI-mediated degranulation and biosynthesis of several lipid raft components. Agents that bypass receptor-mediated Ca(2+) influx stimulate strong degranulation responses in these variant cells. Cross-linking of IgE-Fc epsilon RI on these cells stimulates robust tyrosine phosphorylation but fails to mobilize a sustained Ca(2+) response. Fc epsilon RI-mediated inositol phosphate production is not detectable in these cells, and failure of adenosine receptors to mobilize Ca(2+) suggests a general deficiency in stimulated phospholipase C activity. Antigen stimulation of phospholipases A(2) and D is also defective. Infection of B6A4C1 cells with vaccinia virus constructs expressing constitutively active Rho family members Cdc42 and Rac restores antigen-stimulated degranulation, and active Cdc42 (but not active Rac) restores ganglioside and GPI expression. The results support the hypothesis that activation of Cdc42 and/or Rac is critical for Fc epsilon RI-mediated signaling that leads to Ca(2+) mobilization and degranulation. Furthermore, they suggest that Cdc42 plays an important role in the biosynthesis and expression of certain components of lipid rafts.

  8. Small and intermediate conductance Ca2+-activated K+ channels confer distinctive patterns of distribution in human tissues and differential cellular localisation in the colon and corpus cavernosum

    NARCIS (Netherlands)

    Chen, Mao Xiang; Gorman, Shelby A.; Benson, Bill; Singh, Kuljit; Hieble, J. Paul; Michel, Martin C.; Tate, Simon N.; Trezise, Derek J.

    2004-01-01

    The SK/IK family of small and intermediate conductance calcium-activated potassium channels contains four members, SK1, SK2, SK3 and IK1, and is important for the regulation of a variety of neuronal and non-neuronal functions. In this study we have analysed the distribution of these channels in

  9. Androgen receptor (AR) promotes clear cell renal cell carcinoma (ccRCC) migration and invasion via altering the circHIAT1/miR-195-5p/29a-3p/29c-3p/CDC42 signals.

    Science.gov (United States)

    Wang, Kefeng; Sun, Yin; Tao, Wei; Fei, Xiang; Chang, Chawnshang

    2017-05-28

    Increasing evidence has demonstrated that the androgen receptor (AR) plays important roles to promote the metastasis of clear cell renal cell carcinoma (ccRCC). The detailed mechanisms, especially how AR functions via altering the circular RNAs (circRNAs) remain unclear. Here we identified a new circRNA (named as circHIAT1) whose expression was lower in ccRCCs than adjacent normal tissues. Targeting AR could suppress ccRCC cell progression via increasing circHIAT1 expression. ChIP assay and luciferase assay demonstrated that AR suppressed circHIAT1 expression via regulating its host gene, Hippocampus Abundant Transcript 1 (HIAT1) expression at the transcriptional level. The consequences of AR-suppressed circHIAT1 resulted in deregulating miR-195-5p/29a-3p/29c-3p expressions, which increased CDC42 expression to enhance ccRCC cell migration and invasion. Increasing this newly identified signal via circHIAT1 suppressed AR-enhanced ccRCC cell migration and invasion. Together, these results suggested that circHIAT1 functioned as a metastatic inhibitor to suppress AR-enhanced ccRCC cell migration and invasion. Targeting this newly identified AR-circHIAT1-mediated miR-195-5p/29a-3p/29c-3p/CDC42 signals may help us develop potential new therapies to better suppress ccRCC metastasis. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Weak Localisation in Clean and Highly Disordered Graphene

    International Nuclear Information System (INIS)

    Hilke, Michael; Massicotte, Mathieu; Whiteway, Eric; Yu, Victor

    2013-01-01

    We look at the magnetic field induced weak localisation peak of graphene samples with different mobilities. At very low temperatures, low mobility samples exhibit a very broad peak as a function of the magnetic field, in contrast to higher mobility samples, where the weak localisation peak is very sharp. We analyze the experimental data in the context of the localisation length, which allows us to extract, both the localisation length and the phase coherence length of the samples, regardless of their mobilities. This analysis is made possible by the observation that the localisation length undergoes a generic weak localisation dependence with striking universal properties

  11. Primary localised cutaneous amyloidosis - a systematic review

    DEFF Research Database (Denmark)

    Kaltoft, Britta; Schmidt, Grethe; Lauritzen, Anne Falensteen

    2013-01-01

    Amyloidosis is defined as extracellular deposits of heterogenic, misfolded proteins, amyloid fibrils, in various tissues. The aim of our study was to review the literature and to evaluate the risk of developing systemic amyloidosis (SA) and the risk of local recurrence of primary localised...

  12. Comparing mobile robot localisation algorithms using Kalmtool

    DEFF Research Database (Denmark)

    Mogensen, Lars Valdemar; Hansen, Søren; Ravn, Ole

    2009-01-01

    In this paper we present an estimation platform with simulation capabilities to evaluate methods for localisation of a mobile robot using a feature map. The platform is based on the Kalmtool 4 toolbox which is a set of MATLAB tools for state estimation of nonlinear systems. The toolbox contains...

  13. Search and localisation of CERN buildings

    CERN Multimedia

    TS/FM - Patrimony and Site Information Section

    2005-01-01

    A new, updated version of the web application allowing search and localisation of CERN buildings has been available since 20 May 2005. You can now find a specific building, road, car-park and other information regarding the CERN sites. For comments or enquiries please contact SIG.Support@cern.ch TS/FM - Patrimony and Site Information Section (ISP)

  14. Neuronal NOS localises to human airway cilia.

    Science.gov (United States)

    Jackson, Claire L; Lucas, Jane S; Walker, Woolf T; Owen, Holly; Premadeva, Irnthu; Lackie, Peter M

    2015-01-30

    Airway NO synthase (NOS) isoenzymes are responsible for rapid and localised nitric oxide (NO) production and are expressed in airway epithelium. We sought to determine the localisation of neuronal NOS (nNOS) in airway epithelium due to the paucity of evidence. Sections of healthy human bronchial tissue in glycol methacrylate resin and human nasal polyps in paraffin wax were immunohistochemically labelled and reproducibly demonstrated nNOS immunoreactivity, particularly at the proximal portion of cilia; this immunoreactivity was blocked by a specific nNOS peptide fragment. Healthy human epithelial cells differentiated at an air-liquid interface (ALI) confirmed the presence of all three NOS isoenzymes by immunofluorescence labelling. Only nNOS immunoreactivity was specific to the ciliary axonemeand co-localised with the cilia marker β-tubulin in the proximal part of the ciliary axoneme. We report a novel localisation of nNOS at the proximal portion of cilia in airway epithelium and conclude that its independent and local regulation of NO levels is crucial for normal cilia function. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Generalised two target localisation using passive monopulse radar

    KAUST Repository

    Jardak, Seifallah; Ahmed, Sajid; Alouini, Mohamed-Slim

    2017-01-01

    The simultaneous lobing technique, also known as monopulse technique, has been widely used for fast target localisation and tracking purposes. Many works focused on accurately localising one or two targets lying within a narrow beam centred around

  16. Channelrhodopsin-2 localised to the axon initial segment.

    Directory of Open Access Journals (Sweden)

    Matthew S Grubb

    2010-10-01

    Full Text Available The light-gated cation channel Channelrhodopsin-2 (ChR2 is a powerful and versatile tool for controlling neuronal activity. Currently available versions of ChR2 either distribute uniformly throughout the plasma membrane or are localised specifically to somatodendritic or synaptic domains. Localising ChR2 instead to the axon initial segment (AIS could prove an extremely useful addition to the optogenetic repertoire, targeting the channel directly to the site of action potential initiation, and limiting depolarisation and associated calcium entry elsewhere in the neuron. Here, we describe a ChR2 construct that we localised specifically to the AIS by adding the ankyrinG-binding loop of voltage-gated sodium channels (Na(vII-III to its intracellular terminus. Expression of ChR2-YFP-Na(vII-III did not significantly affect the passive or active electrical properties of cultured rat hippocampal neurons. However, the tiny ChR2 currents and small membrane depolarisations resulting from AIS targeting meant that optogenetic control of action potential firing with ChR2-YFP-Na(vII-III was unsuccessful in baseline conditions. We did succeed in stimulating action potentials with light in some ChR2-YFP-Na(vII-III-expressing neurons, but only when blocking KCNQ voltage-gated potassium channels. We discuss possible alternative approaches to obtaining precise control of neuronal spiking with AIS-targeted optogenetic constructs and propose potential uses for our ChR2-YFP-Na(vII-III probe where subthreshold modulation of action potential initiation is desirable.

  17. Localised Microwave Bursts During ELMs on MAST

    Directory of Open Access Journals (Sweden)

    Freethy Simon

    2015-01-01

    Full Text Available Bursts of microwave emission are observed during ELM events on the Mega Ampère Spherical Tokamak. In agreement with observations on other machines, these bursts are up to 3 orders of magnitude more intense than the thermal background, but are electron cyclotron in nature. The peak in microwave emission is ~20μ before the peak in midplane Dα emission. Using the Synthetic Aperture Microwave Imaging radiometer, we are able to demonstrate that these bursts are often highly spatially localised and preferentially occur at the tokamak midplane. It is hypothesised that the localisation is a result of Doppler resonance broadening for electron Bernstein waves and the high perpendicular electron energies could be the result of pitch angle scattering in high collisionality regions of the plasma.

  18. The Role of Localisation in Advertising Translation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ying

    2016-01-01

    Today, a growing number of international corporations have been seeking to boost their sales on the global scale. To achieve this, adverting, one of the most common way to stimulate consumption, is widely used in which translation is involved because of diverse languages. Thus, how to translate a source advertising in a target culture has a decisive influence on a compa-ny’s marketing. The aim of the target advertising is to sell products to the locals. In this sense, localisation plays a significant role in the translation of advertising. This essay will discuss the importance of localisation in the translation of advertising and analyse cases of English-Chinese advertising translation based on the purpose of advertising and advertising translation.

  19. 'Localised creativity: a life span perspective'

    OpenAIRE

    Worth, Piers J.

    2000-01-01

    This thesis is based around a biographic study of the lives of 40 individuals (24 men and 16 women) with a reputation for creative work in a localised context (such as an organisation). The study examines life span development patterns from birth to middle age (45 - 60 years of age) with data gained by biographic interview and thematic analysis. Participants selected for this study are creative in that they have a reputation for producing new, novel and useful or appropriate contributions in ...

  20. CT-assisted localisation of intracranial processes

    Energy Technology Data Exchange (ETDEWEB)

    Luft, C.; Trenkler, J.; Hammer, B.; Valencak, E.

    1986-01-01

    With the software developed for the SOMATOM DRH computerized tomograph it is possible to mix a ROI into the digital radiogram (topogram) for projection of a lesion, such as a tumor, onto the topogram plane; the software also allows an image reconstruction taking the topogram as a reference image (topogram-initiated reconstruction). Combining these two relatively simple methods, and adding distance measurements in two planes, the neurosurgeon has at his disposal an objective CT-assisted means of precisely localising intracranial processes before surgery.

  1. CT-assisted localisation of intracranial processes

    International Nuclear Information System (INIS)

    Luft, C.; Trenkler, J.; Hammer, B.; Valencak, E.

    1986-01-01

    With the software developed for the SOMATOM DRH computerized tomograph it is possible to mix a ROI into the digital radiogram (topogram) for projection of a lesion, such as a tumor, onto the topogram plane; the software also allows an image reconstruction taking the topogram as a reference image (topogram-initiated reconstruction). Combining these two relatively simple methods, and adding distance measurements in two planes, the neurosurgeon has at his disposal an objective CT-assisted means of precisely localising intracranial processes before surgery. (orig.) [de

  2. Localisation in a Growth Model with Interaction

    Science.gov (United States)

    Costa, M.; Menshikov, M.; Shcherbakov, V.; Vachkovskaia, M.

    2018-05-01

    This paper concerns the long term behaviour of a growth model describing a random sequential allocation of particles on a finite cycle graph. The model can be regarded as a reinforced urn model with graph-based interaction. It is motivated by cooperative sequential adsorption, where adsorption rates at a site depend on the configuration of existing particles in the neighbourhood of that site. Our main result is that, with probability one, the growth process will eventually localise either at a single site, or at a pair of neighbouring sites.

  3. The Anderson model for electron localisation

    International Nuclear Information System (INIS)

    Pruisken, A.M.M.; Schaefer, L.

    1982-01-01

    The Anderson model for localisation problems is treated with field theory employing the replica trick. We show that no valid perturbation theory results out of the usual (S2)2 formalism due to mishandling of symmetries. The problem is reformulated in terms of matrix fields. It is shown that the Anderson model asymptotically exhibits an exact local gauge symmetry. Elimination of massive longitudinal components leads to a non-compact sigma model, obtained earlier for the description of electronic disorder. We thus establish that the Anderson model is in the same universality class as Wegner's gauge invariant real matrix model. (orig.)

  4. To localise or to be localised with Wifi in the Hubei museum?

    NARCIS (Netherlands)

    Verbree, E.; Zlatanova, S.; Van Winden, K.; Van der Laan, E.B.; Makri, A.; Taizhou, L.; Haojun, A.

    2013-01-01

    Indoor localisation is in demand for a variety of applications within the built environment. An overall solution based on a single technology has not yet been determined. The aim of this paper is to gain insight on Signal Strength monitoring by a special kind of WiFi Monitors in comparison to the

  5. A machine-hearing system exploiting head movements for binaural sound localisation in reverberant conditions

    DEFF Research Database (Denmark)

    May, Tobias; Ma, Ning; Wierstorf, Hagen

    2015-01-01

    This paper is concerned with machine localisation of multiple active speech sources in reverberant environments using two (binaural) microphones. Such conditions typically present a problem for ‘classical’ binaural models. Inspired by the human ability to utilise head movements, the current study...

  6. Localisation of the neuropeptide PACAP and its receptors in the rat parathyroid and thyroid glands

    DEFF Research Database (Denmark)

    Fahrenkrug, Jan; Hannibal, Jens

    2011-01-01

    PACAP (pituitary adenylate cyclase activating polypeptide) is widely distributed neuropeptide acting via three subtypes of receptors, PAC(1), VPAC(1) and VPAC(2). Here we examined the localisation and nature of PACAP-immunoreactive nerves in the rat thyroid and parathyroid glands and defined the ...

  7. Passive RFID Localisation Framework in Smart Homes Healthcare Settings.

    Science.gov (United States)

    Alsinglawi, Belal; Liu, Tony; Nguyen, Quang Vinh; Gunawardana, Upul; Maeder, Anthony; Simoff, Simeon

    2016-01-01

    In recent years, Smart Homes have become a solution to benefit impaired individuals and elderly in their daily life settings. In healthcare applications, pervasive technologies have enabled the practicality of personal monitoring using Indoor positioning technologies. Radio-Frequency Identification (RFID) is a promising technology, which is useful for non-invasive tracking of activities of daily living. Many implementations have focused on using battery-enabled tags like in RFID active tags, which require frequent maintenance and they are costly. Other systems can use wearable sensors requiring individuals to wear tags which may be inappropriate for elders. Successful implementations of a tracking system are dependent on multiple considerations beyond the physical performance of the solution, such as affordability and human acceptance. This paper presents a localisation framework using passive RFID sensors. It aims to provide a low cost solution for subject location in Smart Homes healthcare.

  8. Impact source localisation in aerospace composite structures

    Science.gov (United States)

    De Simone, Mario Emanuele; Ciampa, Francesco; Boccardi, Salvatore; Meo, Michele

    2017-12-01

    The most commonly encountered type of damage in aircraft composite structures is caused by low-velocity impacts due to foreign objects such as hail stones, tool drops and bird strikes. Often these events can cause severe internal material damage that is difficult to detect and may lead to a significant reduction of the structure’s strength and fatigue life. For this reason there is an urgent need to develop structural health monitoring systems able to localise low-velocity impacts in both metallic and composite components as they occur. This article proposes a novel monitoring system for impact localisation in aluminium and composite structures, which is able to determine the impact location in real-time without a-priori knowledge of the mechanical properties of the material. This method relies on an optimal configuration of receiving sensors, which allows linearization of well-known nonlinear systems of equations for the estimation of the impact location. The proposed algorithm is based on the time of arrival identification of the elastic waves generated by the impact source using the Akaike Information Criterion. The proposed approach was demonstrated successfully on both isotropic and orthotropic materials by using a network of closely spaced surface-bonded piezoelectric transducers. The results obtained show the validity of the proposed algorithm, since the impact sources were detected with a high level of accuracy. The proposed impact detection system overcomes current limitations of other methods and can be retrofitted easily on existing aerospace structures allowing timely detection of an impact event.

  9. [Morphea or juvenile localised scleroderma: Case report].

    Science.gov (United States)

    Strickler, Alexis; Gallo, Silvanna; Jaramillo, Pedro; de Toro, Gonzalo

    2016-01-01

    Morphea or juvenile localised scleroderma (JLS) is an autoimmune, inflammatory, chronic, slowly progressive connective tissue disease of unknown cause that preferably affects skin and underlying tissues. To report a case of Juvenil Localised scleroderma in an 8-year old girl, contributing to an early diagnosis and treatment. The case is presented of an 8 year-old girl who presented with indurated hypopigmented plaques, of linear distribution in the right upper extremity of two years onset, together with papery texture hyperpigmented indurated plaques with whitish areas of thinned skin in right lower extremity, and leg and ankle swelling. The clinical features and diagnostic tests, including histology were compatible with linear and pansclerotic JLS. She started with immunosuppressive therapy, physiotherapy, and occupational therapy. We report a case of linear and pansclerotic ELJ type, in which there was a 2 year delay in diagnosis, however the response to treatment was positive as expected. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Strain localisation in mechanically layered rocks beneath detachment zones: insights from numerical modelling

    Directory of Open Access Journals (Sweden)

    L. Le Pourhiet

    2013-04-01

    Full Text Available We have designed a series of fully dynamic numerical simulations aimed at assessing how the orientation of mechanical layering in rocks controls the orientation of shear bands and the depth of penetration of strain in the footwall of detachment zones. Two parametric studies are presented. In the first one, the influence of stratification orientation on the occurrence and mode of strain localisation is tested by varying initial dip of inherited layering in the footwall with regard to the orientation of simple shear applied at the rigid boundary simulating a rigid hanging wall, all scaling and rheological parameter kept constant. It appears that when Mohr–Coulomb plasticity is being used, shear bands are found to localise only when the layering is being stretched. This corresponds to early deformational stages for inital layering dipping in the same direction as the shear is applied, and to later stages for intial layering dipping towards the opposite direction of shear. In all the cases, localisation of the strain after only γ=1 requires plastic yielding to be activated in the strong layer. The second parametric study shows that results are length-scale independent and that orientation of shear bands is not sensitive to the viscosity contrast or the strain rate. However, decreasing or increasing strain rate is shown to reduce the capacity of the shear zone to localise strain. In the later case, the strain pattern resembles a mylonitic band but the rheology is shown to be effectively linear. Based on the results, a conceptual model for strain localisation under detachment faults is presented. In the early stages, strain localisation occurs at slow rates by viscous shear instabilities but as the layered media is exhumed, the temperature drops and the strong layers start yielding plastically, forming shear bands and localising strain at the top of the shear zone. Once strain localisation has occured, the deformation in the shear band becomes

  11. Localisation of metastatic carcinoma by a radiolabelled monoclonal antibody

    Energy Technology Data Exchange (ETDEWEB)

    Smedley, H M; Ritson, A; Wraight, P; Sikora, K [Addenbrooke' s Hospital, Cambridge (UK); Hinchingbrooke Hospital, Huntingdon (UK)); Finan, P [St. James Hospital, Leeds (UK); Lennox, E S; Takei, F [Medical Research Council, Cambridge (UK)

    1983-02-01

    Rat monoclonal antibodies were prepared by immunising rats with human colorectal carcinoma cell membranes and fusing splenic lymphocytes with a rat myeloma. Hybridoma supernatants were screened by binding assays on membranes prepared from colorectal carcinoma tissue. One hybridoma supernatant, containing a monoclonal antibody with high binding activity on malignant compared to normal colon sections, was grown in large quantities in serum-free medium. After ammonium sulphate precipitation the antibody was purified by ion-exchange chromatography and labelled with /sup 131/I. Radiolabelled antibody was administered i.v. to 27 patients with colonic and other tumours. Scintigrams were obtained at 48 h. Computerised subtraction of the blood pool image revealed localised areas of uptake corresponding with areas of known disease in 13/16 patients with colorectal carcinoma and 3/4 patients with breast cancer.

  12. An innovative localisation algorithm for railway vehicles

    Science.gov (United States)

    Allotta, B.; D'Adamio, P.; Malvezzi, M.; Pugi, L.; Ridolfi, A.; Rindi, A.; Vettori, G.

    2014-11-01

    In modern railway automatic train protection and automatic train control systems, odometry is a safety relevant on-board subsystem which estimates the instantaneous speed and the travelled distance of the train; a high reliability of the odometry estimate is fundamental, since an error on the train position may lead to a potentially dangerous overestimation of the distance available for braking. To improve the odometry estimate accuracy, data fusion of different inputs coming from a redundant sensor layout may be used. The aim of this work has been developing an innovative localisation algorithm for railway vehicles able to enhance the performances, in terms of speed and position estimation accuracy, of the classical odometry algorithms, such as the Italian Sistema Controllo Marcia Treno (SCMT). The proposed strategy consists of a sensor fusion between the information coming from a tachometer and an Inertial Measurements Unit (IMU). The sensor outputs have been simulated through a 3D multibody model of a railway vehicle. The work has provided the development of a custom IMU, designed by ECM S.p.a, in order to meet their industrial and business requirements. The industrial requirements have to be compliant with the European Train Control System (ETCS) standards: the European Rail Traffic Management System (ERTMS), a project developed by the European Union to improve the interoperability among different countries, in particular as regards the train control and command systems, fixes some standard values for the odometric (ODO) performance, in terms of speed and travelled distance estimation. The reliability of the ODO estimation has to be taken into account basing on the allowed speed profiles. The results of the currently used ODO algorithms can be improved, especially in case of degraded adhesion conditions; it has been verified in the simulation environment that the results of the proposed localisation algorithm are always compliant with the ERTMS requirements

  13. Enantioselective cellular localisation of europium(iii) coordination complexes.

    Science.gov (United States)

    Frawley, Andrew T; Linford, Holly V; Starck, Matthieu; Pal, Robert; Parker, David

    2018-01-28

    The selective mitochondrial localisation of the Λ enantiomer of three different emissive europium(iii) complexes in NIH 3T3 and MCF7 cells contrasts with the behaviour of the Δ enantiomer, for which a predominant lysosomal localisation was observed by confocal microscopy. In each case, cell uptake occurs via macropinocytosis.

  14. Differences in finger localisation performance of patients with finger agnosia

    NARCIS (Netherlands)

    Anema, H.A.; Kessels, R.P.C.; de Haan, E.H.F.; Kappelle, L.J.; Leijten, F.S.; van Zandvoort, M.J.E.; Dijkerman, H.C.

    2008-01-01

    Several neuropsychological studies have suggested parallel processing of somatosensory input when localising a tactile stimulus on one's own by pointing towards it (body schema) and when localising this touched location by pointing to it on a map of a hand (body image). Usually these reports

  15. Differences in finger localisation performance of patients with finger agnosia

    NARCIS (Netherlands)

    Anema, H.A.; Kessels, R.P.C.; Haan, E.H.F. de; Kappelle, L.J.; Leijten, F.S.S.; Zandvoort, M.J.E. van; Dijkerman, H.C.

    2008-01-01

    Several neuropsychological studies have suggested parallel processing of somatosensory input when localising a tactile stimulus on ones own by pointing towards it (body schema) and when localising this touched location by pointing to it on a map of a hand (body image). Usually these reports describe

  16. Differences in finger localisation performance of patients with finger agnosia.

    NARCIS (Netherlands)

    Anema, H.A.; Kessels, R.P.C.; Haan, E.H.F. de; Kappelle, L.J.; Leijten, F.S.S.; Zandvoort, M.J. Van; Dijkerman, H.C.

    2008-01-01

    Several neuropsychological studies have suggested parallel processing of somatosensory input when localising a tactile stimulus on one's own by pointing towards it (body schema) and when localising this touched location by pointing to it on a map of a hand (body image). Usually these reports

  17. Localisation system in wireless sensor networks using ns-2

    CSIR Research Space (South Africa)

    Abu-Mahfouz, Adnan M

    2012-04-01

    Full Text Available -1 /************************************************************************** ********** * * File: readme.asn * * Author: Adnan Abu-Mahfouz * * Date: March 2012 * * Description: Localisation system in wireless sensor networks using ns-2... *************************************************************************** *********/ /************************************************************************** *************************************************************************** *****/ 1. Introduction: ns-2 contains several flexible features that encourage researchers to use ns-2 to investigate the characteristics of wireless sensor networks (WSNs). However, to implement and evaluate localisation algorithms, the current ns- 2...

  18. Amelogenesis imperfecta and localised aggressive periodontitis: A rare clinical entity

    Directory of Open Access Journals (Sweden)

    Gayatri Gundannavar

    2013-01-01

    Full Text Available This case report presents two female patients whose chief complaint was discoloration of teeth. On careful clinical examination it was found that the patients had features of amelogenesis imperfecta and localised aggressive periodontitis. This article will give an insight of clinical and radiographic features of amelogenesis imperfecta with localised aggressive periodontitis, which is a rare clinical entity.

  19. Feasibility of magnetic marker localisation for non-palpable breast cancer

    NARCIS (Netherlands)

    Schermers, B.; van der Hage, Jos A.; Loo, C.E.; Vrancken Peeters, M.T.F.D.; Winter-Warnars, H. A.O.; Duijnhoven, F.H.; ten Haken, B.; Muller, S.H.; Ruers, T. J.M.

    2017-01-01

    Objectives Accurate tumour localisation is essential for breast-conserving surgery of non-palpable tumours. Current localisation technologies are associated with disadvantages such as logistical challenges and migration issues (wire guided localisation) or legislative complexities and high

  20. Cloning and differential expression analyses of Cdc42 from sheep

    Directory of Open Access Journals (Sweden)

    Yang Yong-Jie

    2018-03-01

    Full Text Available Introduction: Serological diagnosis of brucellosis is still a great challenge due to the infeasibility of discriminating infected animals from vaccinated ones, so it is necessary to search for diagnostic biomarkers for differential diagnosis of brucellosis.

  1. Localised states in organic semiconductors and their detection

    Science.gov (United States)

    Imperia, Paolo

    2002-06-01

    oxadiazoles, studied because of their technological relevance, show complex thermograms, having several levels of localised states and depolarisation peaks. In particular well ordered films of an amphiphilic substituted 2-(p-nitrophenyl)-5-(p-undecylamidophenyl)-1,3,4-oxadiazole (NADPO) are characterised by rich TSL thermograms. A wide region of shallow traps, localised at Em = 4 meV, has been successfully fit by means of a first order kinetic equation having a Gaussian distribution of localised states. Two further peaks, having a different origin, have been characterised. The peaks at Tm = 221.5 K and Tm = 254.2 have activation energy of Em= 0.63 eV and Em = 0.66 eV, frequency factor s = 2.4x1012 s-1 and s = 1.85x1011 s-1, distribution width s = 0.045 eV and s = 0.088 eV respectively. Increasing the number of thermal cycle, a peak, probably connected with structural defects, appears at Tm = 197.7 K. The numerical analysis of this peak was performed by means of a first order equation containing a Gaussian distribution of traps. The activation energy of the trap level is centred at Em = 0.55 eV. The distribution is perfectly symmetric with a quite small width s = 0.028 eV. The frequency factor is s = 1.15 x 1012 s-1, resulting of the same order of magnitude of its neighbour peak at Tm = 221.5 K, having both, probably, the same origin. Furthermore the work demonstrates that the shape of the glow curves is strongly influenced by the excitation temperature and by the thermal cycles. For that reason Gaussian distributions of localised states can be confused with exponential distributions if the previous thermal history of the samples is not adequately considered. In den letzten Jahren ist eine Vielzahl neuer organischer Polymere und niedermolekularer Verbindungen synthetisiert worden, die sich als aktive Komponente für Elektrolumineszenz-Bauelemente und andere elektronische Anwendungen eignen. Trotz der großen technologischen Bedeutung und des erheblichen Fortschrittes, der bei

  2. Generalised two target localisation using passive monopulse radar

    KAUST Repository

    Jardak, Seifallah

    2017-04-07

    The simultaneous lobing technique, also known as monopulse technique, has been widely used for fast target localisation and tracking purposes. Many works focused on accurately localising one or two targets lying within a narrow beam centred around the monopulse antenna boresight. In this study, a new approach is proposed, which uses the outputs of four antennas to rapidly localise two point targets present in the hemisphere. If both targets have the same elevation angle, the proposed scheme cannot detect them. To detect such targets, a second set of antennas is required. In this study, to detect two targets at generalised locations, the antenna array is divided into multiple overlapping sets each of four antennas. Two algorithms are proposed to combine the outputs from multiple sets and improve the detection performance. Simulation results show that the algorithm is able to localise both targets with <;2° mean square error in azimuth and elevation.

  3. Is the Pauli exclusion principle the origin of electron localisation?

    Science.gov (United States)

    Rincón, Luis; Torres, F. Javier; Almeida, Rafael

    2018-03-01

    In this work, we inquire into the origins of the electron localisation as obtained from the information content of the same-spin pair density, γσ, σ(r2∣r1). To this end, we consider systems of non-interacting and interacting identical Fermions contained in two simple 1D potential models: (1) an infinite potential well and (2) the Kronig-Penney periodic potential. The interparticle interaction is considered through the Hartree-Fock approximation as well as the configuration interaction expansion. Morover, the electron localisation is described through the Kullback-Leibler divergence between γσ, σ(r2∣r1) and its associated marginal probability. The results show that, as long as the adopted method properly includes the Pauli principle, the electronic localisation depends only modestly on the interparticle interaction. In view of the latter, one may conclude that the Pauli principle is the main responsible for the electron localisation.

  4. Critical Factors in Transnational Oil Companies Localisation Decisions - Clusters and Portfolio Optimisation

    International Nuclear Information System (INIS)

    Kind, Hans Jarle; Osmundsen, Petter; Tverteraas, Ragnar

    2001-10-01

    Enhanced understanding of the factors determining trans national companies' localisation decisions is important for regulators and other stake holders concerned about maintaining current activity levels in a petroleum producing country. This article discusses localisation decisions in the context of theories of industrial clusters and real portfolio optimisation theory (materiality), which we argue are two fruitful lines of explanation for trans national companies' behaviour. The industrial cluster literature is concerned about the level of positive externalities associated with geographic clustering of related production activities. The concept of materiality, implying that investment projects in an oil province must be of a certain minimum size in order to be interesting for oil companies, is evaluated empirically and compared to predictions of mainstream economic theory. (author)

  5. Critical Factors in Transnational Oil Companies Localisation Decisions - Clusters and Portfolio Optimisation

    Energy Technology Data Exchange (ETDEWEB)

    Kind, Hans Jarle; Osmundsen, Petter; Tverteraas, Ragnar

    2001-10-01

    Enhanced understanding of the factors determining transnational companies' localisation decisions is important for regulators and other stakeholders concerned about maintaining current activity levels in a petroleum producing country. This article discusses localisation decisions in the context of theories of industrial clusters and real portfolio optimisation theory (materiality), which we argue are two fruitful lines of explanation for transnational companies' behaviour. The industrial cluster literature is concerned about the level of positive externalities associated with geographic clustering of related production activities. The concept of materiality, implying that investment projects in an oil province must be of a certain minimum size in order to be interesting for oil companies, is evaluated empirically and compared to predictions of mainstream economic theory. (author)

  6. Immunohistochemical localisation of d-β-aspartic acid in pingueculae

    OpenAIRE

    Kaji, Y; Oshika, T; Okamoto, F; Fujii, N

    2009-01-01

    Background: D-β-Aspartic acid residues, which are biologically uncommon, have been reported to accumulate in various proteins of the living body with age. In the present study, D-β-aspartic acid-containing proteins were found to be localised in pingueculae, which represent one of the most prominent age-related ocular changes.Methods: Surgical specimens of conjunctivae with or without pingueculae were obtained from eight patients. Immunohistochemical localisation of D-β-aspartic acid-containin...

  7. Indoor Localisation Based on GSM Signals: Multistorey Building Study

    Directory of Open Access Journals (Sweden)

    Rafał Górak

    2016-01-01

    Full Text Available Among the accurate indoor localisation systems that are using WiFi, Bluetooth, or infrared technologies, the ones that are based on the GSM rely on a stable external infrastructure that can be used even in an emergency. This paper presents an accurate GSM indoor localisation system that achieves a median error of 4.39 metres in horizontal coordinates and up to 64 percent accuracy in floor prediction (for 84 percent of cases the floor prediction is mistaken by not more than a single floor. The test and reference measurements were made inside a six-floor academic building, with an irregular shape, whose dimensions are around 50 metres by 70 metres. The localisation algorithm uses GSM signal readings from the 7 strongest cells available in the GSM standard (or fewer, if fewer than 7 are available. We estimate the location by a three-step method. Firstly, we propose a point localisation solution (i.e., localisation based on only one measurement. Then, by applying the central tendency filters and the Multilayer Perceptron, we build a localisation system that uses a sequence of estimations of current and past locations. We also discuss major accuracy factors such as the number of observed signals or the types of spaces in the building.

  8. Localising welfare-to-work? Territorial flexibility and the New Deal for Young People

    OpenAIRE

    Corinne Nativel; Peter Sunley; Ron Martin

    2002-01-01

    The move towards workfare and active labour-market policies is often alleged to be closely associated with the decentralisation and localisation of welfare delivery and agencies. In the United Kingdom, the New Deal for the young unemployed was designed to introduce local flexibility and discretion in delivery to mainstream labour-market policy. We use case studies of five local areas to examine the extent to which the programme has actually been decentralised and benefited from 'local flexibi...

  9. Antenna array geometry optimization for a passive coherent localisation system

    Science.gov (United States)

    Knott, Peter; Kuschel, Heiner; O'Hagan, Daniel

    2012-11-01

    Passive Coherent Localisation (PCL), also known as Passive Radar, making use of RF sources of opportunity such as Radio or TV Broadcasting Stations, Cellular Phone Network Base Stations, etc. is an advancing technology for covert operation because no active radar transmitter is required. It is also an attractive addition to existing active radar stations because it has the potential to discover low-flying and low-observable targets. The CORA (Covert Radar) experimental passive radar system currently developed at Fraunhofer-FHR features a multi-channel digital radar receiver and a circular antenna array with separate elements for the VHF- and the UHF-range and is used to exploit alternatively Digital Audio (DAB) or Video Broadcasting (DVB-T) signals. For an extension of the system, a wideband antenna array is being designed for which a new discone antenna element has been developed covering the full DVB-T frequency range. The present paper describes the outline of the system and the numerical modelling and optimisation methods applied to solve the complex task of antenna array design: Electromagnetic full wave analysis is required for the parametric design of the antenna elements while combinatorial optimization methods are applied to find the best array positions and excitation coefficients for a regular omni-directional antenna performance. The different steps are combined in an iterative loop until the optimum array layout is found. Simulation and experimental results for the current system will be shown.

  10. Localised task-dependent motor-unit recruitment in the masseter.

    Science.gov (United States)

    Schindler, H J; Hellmann, D; Giannakopoulos, N N; Eiglsperger, U; van Dijk, J P; Lapatki, B G

    2014-07-01

    Localised motor-unit (MU) recruitment in the masseter was analysed in this study. We investigated whether differential activation behaviour, which has already been reported for distant masseter regions, can also be detected in small muscle subvolumes at the level of single MUs. Two bipolar fine-wire electrodes and an intra-oral 3D bite-force transmitter were used to record intra-muscular electromyograms (EMG) resulting from controlled bite-forces of 10 healthy human subjects (mean age 24.1 ± 1.2 years). Two-hundred and seventeen decomposed MUs were organised into localised MU task groups with different (P < 0.001) force-direction-specific behaviour. Proportions of MUs involved in one, two, three or four examined tasks were 46%, 31%, 18% and 5%, respectively. This study provides evidence of the ability of the neuromuscular system to modify the mechanical output of small masseter subvolumes by differential control of adjacent MUs belonging to distinct task groups. Localised differential activation behaviour of the masseter may be the crucial factor enabling highly flexible and efficient adjustment of the muscle activity in response to complex local biomechanical needs, for example, continually varying bite-forces during the demanding masticatory process. © 2014 John Wiley & Sons Ltd.

  11. Protein Tyrosine Phosphatase-PEST and β8 Integrin Regulate Spatiotemporal Patterns of RhoGDI1 Activation in Migrating Cells

    Science.gov (United States)

    Lee, Hye Shin; Cheerathodi, Mujeeburahiman; Chaki, Sankar P.; Reyes, Steve B.; Zheng, Yanhua; Lu, Zhimin; Paidassi, Helena; DerMardirossian, Celine; Lacy-Hulbert, Adam; Rivera, Gonzalo M.

    2015-01-01

    Directional cell motility is essential for normal development and physiology, although how motile cells spatiotemporally activate signaling events remains largely unknown. Here, we have characterized an adhesion and signaling unit comprised of protein tyrosine phosphatase (PTP)-PEST and the extracellular matrix (ECM) adhesion receptor β8 integrin that plays essential roles in directional cell motility. β8 integrin and PTP-PEST form protein complexes at the leading edge of migrating cells and balance patterns of Rac1 and Cdc42 signaling by controlling the subcellular localization and phosphorylation status of Rho GDP dissociation inhibitor 1 (RhoGDI1). Translocation of Src-phosphorylated RhoGDI1 to the cell's leading edge promotes local activation of Rac1 and Cdc42, whereas dephosphorylation of RhoGDI1 by integrin-bound PTP-PEST promotes RhoGDI1 release from the membrane and sequestration of inactive Rac1/Cdc42 in the cytoplasm. Collectively, these data reveal a finely tuned regulatory mechanism for controlling signaling events at the leading edge of directionally migrating cells. PMID:25666508

  12. Pharmacologic modulation of protein kinase C isozymes: the role of RACKs and subcellular localisation.

    Science.gov (United States)

    Csukai, M; Mochly-Rosen, D

    1999-04-01

    Protein kinase C (PKC) isozymes are highly homologous kinases and several different isozymes can be present in a cell. Each isozyme is likely to mediate unique functions, but pharmacological tools to explore their isozyme-specific roles have not been available until recently. In this review, we describe the development and application of isozyme-selective inhibitors of PKC. The identification of these inhibitors stems from the observation that PKC isozymes are each localised to unique subcellular locations following activation. Inhibitors of this isozyme-unique localisation have been shown to act as selective inhibitors of the functions of individual isozymes. The identification of isozyme-specific inhibitors should allow the exploration of individual PKC isozyme function in a wide range of cell systems. Copyright 1999 The Italian Pharmacological Society.

  13. Localisation of Neuregulin 1-{beta}3 to different sub-nuclear structures alters gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ming; Trim, Carol M.; Gullick, William J., E-mail: w.j.gullick@kent.ac.uk

    2011-02-15

    Neuregulins are growth factors that signal via the ErbB3 and ErbB4 receptors. Here we show using immunohistochemistry that they are often expressed in the nucleus of a range of tumour types including soft tissue and breast. The Neuregulin 1 type I-{beta}3 (NRG1-{beta}3) isoform localises to two sub-nuclear compartments in animal cells, nucleoli and spliceosomes. We used NRG1-{beta}3 tagged with photoactivatable GFP and demonstrated that this re-localised from nucleoli to spliceosomes over 90 min. Tyrosine kinase activity was not required for retaining the NRG1-{beta}3 within the nucleus. Mutation of the lysines 14 and 16 or 15 and 16 together prevented nucleolar uptake while four positively charged residues were identified which were required for spliceosome uptake. Molecular modelling suggests that three of these may form a binding site. We showed using a kinome array that NRG1-{beta}3 and a mutant exclusively localising to spliceosomes increased phosphorylation and/or expression of the HER4 and HER2 receptors. Using a transcriptomic analysis the same two constructs induced expression of several messenger RNAs and we confirmed the increased expression at the protein level of the most highly induced, Heat Shock Protein 70B'. These results suggest that Neuregulin activates receptor signalling in spliceosomes leading to altered gene expression.

  14. Localisation of Neuregulin 1-β3 to different sub-nuclear structures alters gene expression

    International Nuclear Information System (INIS)

    Wang, Ming; Trim, Carol M.; Gullick, William J.

    2011-01-01

    Neuregulins are growth factors that signal via the ErbB3 and ErbB4 receptors. Here we show using immunohistochemistry that they are often expressed in the nucleus of a range of tumour types including soft tissue and breast. The Neuregulin 1 type I-β3 (NRG1-β3) isoform localises to two sub-nuclear compartments in animal cells, nucleoli and spliceosomes. We used NRG1-β3 tagged with photoactivatable GFP and demonstrated that this re-localised from nucleoli to spliceosomes over 90 min. Tyrosine kinase activity was not required for retaining the NRG1-β3 within the nucleus. Mutation of the lysines 14 and 16 or 15 and 16 together prevented nucleolar uptake while four positively charged residues were identified which were required for spliceosome uptake. Molecular modelling suggests that three of these may form a binding site. We showed using a kinome array that NRG1-β3 and a mutant exclusively localising to spliceosomes increased phosphorylation and/or expression of the HER4 and HER2 receptors. Using a transcriptomic analysis the same two constructs induced expression of several messenger RNAs and we confirmed the increased expression at the protein level of the most highly induced, Heat Shock Protein 70B'. These results suggest that Neuregulin activates receptor signalling in spliceosomes leading to altered gene expression.

  15. Quality of Life Outcomes after Primary Treatment for Clinically Localised Prostate Cancer: A Systematic Review.

    Science.gov (United States)

    Lardas, Michael; Liew, Matthew; van den Bergh, Roderick C; De Santis, Maria; Bellmunt, Joaquim; Van den Broeck, Thomas; Cornford, Philip; Cumberbatch, Marcus G; Fossati, Nicola; Gross, Tobias; Henry, Ann M; Bolla, Michel; Briers, Erik; Joniau, Steven; Lam, Thomas B; Mason, Malcolm D; Mottet, Nicolas; van der Poel, Henk G; Rouvière, Olivier; Schoots, Ivo G; Wiegel, Thomas; Willemse, Peter-Paul M; Yuan, Cathy Yuhong; Bourke, Liam

    2017-12-01

    Current evidence-based management for clinically localised prostate cancer includes active surveillance, surgery, external beam radiotherapy (EBRT) and brachytherapy. The impact of these treatment modalities on quality of life (QoL) is uncertain. To systematically review comparative studies investigating disease-specific QoL outcomes as assessed by validated cancer-specific patient-reported outcome measures with at least 1 yr of follow-up after primary treatment for clinically localised prostate cancer. MEDLINE, EMBASE, AMED, PsycINFO, and Cochrane Library were searched to identify relevant studies. Studies were critically appraised for the risk of bias. A narrative synthesis was undertaken. Of 11486 articles identified, 18 studies were eligible for inclusion, including three randomised controlled trials (RCTs; follow-up range: 60-72 mo) and 15 nonrandomised comparative studies (follow-up range: 12-180 mo) recruiting a total of 13604 patients. Two RCTs recruited small cohorts and only one was judged to have a low risk of bias. The quality of evidence from observational studies was low to moderate. For a follow-up of up to 6 yr, active surveillance was found to have the lowest impact on cancer-specific QoL, surgery had a negative impact on urinary and sexual function when compared with active surveillance and EBRT, and EBRT had a negative impact on bowel function when compared with active surveillance and surgery. Data from one small RCT reported that brachytherapy has a negative impact on urinary function 1 yr post-treatment, but no significant urinary toxicity was reported at 5 yr. This is the first systematic review comparing the impact of different primary treatments on cancer-specific QoL for men with clinically localised prostate cancer, using validated cancer-specific patient-reported outcome measures only. There is robust evidence that choice of primary treatment for localised prostate cancer has distinct impacts on patients' QoL. This should be discussed in

  16. Intracellular localisation of proteins to specific cellular areas by nanocapsule mediated delivery.

    Science.gov (United States)

    Wang, Huabin; Chen, Ligang; Sun, Xianchao; Fu, Ailing

    2017-09-01

    Nanocapsules are promising carriers with great potential for intracellular protein transport. Although many studies have intended to improve cell uptake efficacy, there is an increasing interest in understanding of subcellular distribution of cargoes inside cells, which is essential for purposeful delivery of biomolecules into specific sites within cells. Herein, we interrogate the intracellular localisation of exogenous proteins, including fluorescein isothiocyanate (FITC)-labelled bovine serum albumin (BSA) and green fluorescent protein (GFP), mediated by specially designed nanocapsules. The results show that the designed nanocapsules can deliver the two types of fluorescent proteins into different cellular destinations (cytosol, nucleus or the whole cell), depending on the composition of nanocapsules. Meanwhile, several impact factors that influence the distribution of proteins in cells have also been investigated, and the results suggest that the localisation of capsule-mediated proteins in cells is strongly affected by the surface properties of nanocapsules, the types of stabilisers and proteins, and environmental temperatures. The rational control of intracellular localised delivery of exogenous proteins as we demonstrated in this study might open new avenues to obtain desired magnitude of drug effects for modulating cell activity.

  17. Localisation of beam offset jitter sources at ATF2

    CERN Document Server

    Pfingstner, J; Patecki, M; Schulte, D; Tomás, R

    2014-01-01

    For the commissioning and operation of modern particle accelerators, automated error detection and diagnostics methods are becoming increasingly important. In this paper, we present two such methods, which are capable of localising sources of beam offset jitter with a combination of correlation studies and so called degree of freedom plots. The methods were applied to the ATF2 beam line at KEK, where one of the major goals is the reduction of the beam offset jitter. Results of this localisation are shown in this paper. A big advantage of the presented method is its high robustness especially to varying optics parameters. Therefore, we believe that the developed beam offset jitter localisation methods can be easily applied to other accelerators.

  18. Differences in finger localisation performance of patients with finger agnosia.

    Science.gov (United States)

    Anema, Helen A; Kessels, Roy P C; de Haan, Edward H F; Kappelle, L Jaap; Leijten, Frans S; van Zandvoort, Martine J E; Dijkerman, H Chris

    2008-09-17

    Several neuropsychological studies have suggested parallel processing of somatosensory input when localising a tactile stimulus on one's own by pointing towards it (body schema) and when localising this touched location by pointing to it on a map of a hand (body image). Usually these reports describe patients with impaired detection, but intact sensorimotor localisation. This study examined three patients with a lesion of the angular gyrus with intact somatosensory processing, but with selectively disturbed finger identification (finger agnosia). These patients performed normally when pointing towards the touched finger on their own hand but failed to indicate this finger on a drawing of a hand or to name it. Similar defects in the perception of other body parts were not observed. The findings provide converging evidence for the dissociation between body image and body schema and, more importantly, reveal for the first time that this distinction is also present in higher-order cognitive processes selectively for the fingers.

  19. An ultrastructural and irradiation study of diffuse and localised kinetochore

    International Nuclear Information System (INIS)

    Bokhari, F.S.

    1979-05-01

    An electron microscope study of plant types Luzula nivea and Cyperus eragrostis with diffuse kinetochores and Crepis neglecta with localised kinetochore showed that Luzula has a rather different kinetochore organisation from Cyperus, with features approaching the localised type of Crepis. These studies included an examination of the ultrastructure of the kinetochore at metaphase at low magnification in control and irradiated material of Luzula; the chromosomal ultrastructure at high magnification at interphase and all stages of mitosis in Luzula, Cyperus and Crepis; and the ultrastructure of the nucleolus in Luzula, Cyperus and Crepis. Light microscopic studies were also performed showing the effects of irradiation on first mitotic division in Cyperus, Luzula and Crepis, mitotic aberrations in Cyperus and Crepis and meiosis in Cyperus. Finally, the survival with the diffuse as opposed to the localised kinetochore in M 1 and M 2 generations following seed irradiation was studied. (U.K.)

  20. Monitoring corrosion rates and localised corrosion in low conductivity water

    DEFF Research Database (Denmark)

    Hilbert, Lisbeth Rischel

    2006-01-01

    Monitoring of low corrosion rates and localised corrosion in a media with low conductivity is a challenge. In municipal district heating, quality control may be improved by implementing on-line corrosion monitoring if a suitable technique can be identified to measure both uniform and localised...... corrosion. Electrochemical techniques (LPR, EIS, crevice corrosion current) as well as direct measurement techniques (high-sensitive electrical resistance, weight loss) have been applied in operating plants. Changes in the corrosion processes are best monitored in non-aggressive, low conductivity media...

  1. Experimental investigation of edge localised modes in JET

    International Nuclear Information System (INIS)

    Lindholm Colton, A.

    1993-08-01

    Edge Localised Modes (ELMs) in the JET tokamak have been studied experimentally, using density profile and fluctuation data from a multichannel reflectometer and temperature profile data from an ECE heterodyne radiometer. The following topics have been investigated: The radial extent and localisation of the density and temperature profile perturbations caused by the ELMs. Fluctuations in the density and magnetic field in connection with the ELMs. The correlation between the repetition frequency of the L-H transition ELMs, and the plasma edge temperature and density. Trajectories in n-T space prior to ELMs later in the H-mode. (au) (39 refs.)

  2. Correlative and integrated light and electron microscopy of in-resin GFP fluorescence, used to localise diacylglycerol in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Peddie, Christopher J.; Blight, Ken; Wilson, Emma [Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY (United Kingdom); Melia, Charlotte [Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY (United Kingdom); Cell Biophysics Laboratory, London Research Institute, Cancer Research UK, London WC2A 3LY (United Kingdom); Department of Molecular Cell Biology, Leiden University Medical Centre, 2300 RC Leiden (Netherlands); Marrison, Jo [Department of Biology, The University of York, Heslington, York (United Kingdom); Carzaniga, Raffaella [Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY (United Kingdom); Domart, Marie-Charlotte [Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY (United Kingdom); Cell Biophysics Laboratory, London Research Institute, Cancer Research UK, London WC2A 3LY (United Kingdom); O' Toole, Peter [Department of Biology, The University of York, Heslington, York (United Kingdom); Larijani, Banafshe [Cell Biophysics Laboratory, London Research Institute, Cancer Research UK, London WC2A 3LY (United Kingdom); Cell Biophysics Laboratory, Unidad de Biofísica (CSIC-UPV/EHU),Sarriena s/n, 48940 Leioa (Spain); IKERBASQUE, Basque Foundation for Science, Bilbao (Spain); Collinson, Lucy M. [Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY (United Kingdom)

    2014-08-01

    Fluorescence microscopy of GFP-tagged proteins is a fundamental tool in cell biology, but without seeing the structure of the surrounding cellular space, functional information can be lost. Here we present a protocol that preserves GFP and mCherry fluorescence in mammalian cells embedded in resin with electron contrast to reveal cellular ultrastructure. Ultrathin in-resin fluorescence (IRF) sections were imaged simultaneously for fluorescence and electron signals in an integrated light and scanning electron microscope. We show, for the first time, that GFP is stable and active in resin sections in vacuo. We applied our protocol to study the subcellular localisation of diacylglycerol (DAG), a modulator of membrane morphology and membrane dynamics in nuclear envelope assembly. We show that DAG is localised to the nuclear envelope, nucleoplasmic reticulum and curved tips of the Golgi apparatus. With these developments, we demonstrate that integrated imaging is maturing into a powerful tool for accurate molecular localisation to structure. - Highlights: • GFP and mCherry fluorescence are preserved in heavy-metal stained mammalian cells embedded in resin • Fluorophores are stable and intensity is sufficient for detection in ultrathin sections • Overlay of separate LM and EM images from the same ultrathin section improves CLEM protein localisation precision • GFP is stable and active in the vacuum of an integrated light and scanning EM • Integrated light and electron microscopy shows new subcellular locations of the lipid diacylglycerol.

  3. Application of a Null-Beamformer to Source Localisation in MEG Data of Deep Brain Stimulation

    DEFF Research Database (Denmark)

    Mohseni, Hamid R.; Kringelbach, Morten L.; Smith, Penny Probert

    2010-01-01

    In this paper, we present an analysis of magnetoencephalography (MEG) signals from a patient with whole-body chronic pain in order to investigate changes in neural activity induced by DBS. The patient is one of the few cases treated using DBS of the anterior cingulate cortex (ACC). Using MEG...... the accuracy of our source localisation by correlating the predicted DBS electrode positions with their actual positions, previously identified using anatomical imaging. We also demonstrated increased activity in pain-related regions including the pre-supplementary motor area, brainstem periaqueductal gray...

  4. Characterisation of a novel proteolytic enzyme localised to goblet cells in rat and man

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier

    1984-01-01

    A proteolytic enzyme, ingobsin , purified from rat duodenal extracts is shown to be localised to intestinal goblet cells of both man and rat. Enzyme positive cells decrease in number from duodenum to colon. The enzyme is a 33 000 Mr protein with an isoelectric point of 5.1. The pH optimum...... for enzymatic activity is 7.4-8.0. Based on substrate specificity for arg-x, lys-x and to a lesser degree tyr-x, on the effect of diisopropylphosphorofluoride , Trasylol and phenylmethylsulfonylfluoride and on proteolytic activity towards intact proteins, ingobsin is classified as a serine proteinase...

  5. Time Localisation of Surface Defects on Optical Discs

    DEFF Research Database (Denmark)

    Odgaard, Peter Fogh; Wickerhauser, M.V.

    Many have experienced problems with their Compact Disc player when a disc with a scratch or a finger print is tried played. One way to improve the playability of discs with such a defect, is to locate the defect in time and then handle it in a special way. As a consequence this time localisation...

  6. Immunogold staining procedure for the localisation of regulatory peptides.

    Science.gov (United States)

    Varndell, I M; Tapia, F J; Probert, L; Buchan, A M; Gu, J; De Mey, J; Bloom, S R; Polak, J M

    1982-01-01

    The use of protein A- and IgG-conjugated colloidal gold staining methods for the immuno-localisation of peptide hormones and neurotransmitters at light- and electron microscope level are described and discussed. Bright-field and dark-ground illumination modes have been used to visualise the gold-labelled antigenic sites at the light microscope level. Immunogold staining procedures at the ultrastructural level using region-specific antisera have been adopted to localise specific molecular forms of peptides including gastrin (G17 and G34), glucagon and pro-glucagon, insulin and pro-insulin, in normal tissue and in tumours of the gastroenteropancreatic system. Similar methods have been used to demonstrate the heterogeneity of p-type nerves in the enteric nervous system. Vasoactive intestinal polypeptide (VIP) has been localised to granular sites (mean +/- S.D. granule diameter = 98 +/- 19 nm) in nerve terminals of the enteric plexuses and in tumour cells of diarrhoeogenic VIP-producing neoplasias (mean +/- S.D. granule diameter = 126 +/- 37 nm) using immunogold procedures applied to ultraviolet-cured ultrathin sections. Co-localisation of amines and peptides in carotid body type I cells and in chromaffin cells of normal adrenal medulla and phaeochromocytomas has also been demonstrated. Advantages of the immunogold procedures over alternative immunocytochemical techniques are discussed.

  7. Human SLAM, indoor localisation of devices and users

    NARCIS (Netherlands)

    Bulten, W.; Rossum, A.C. van; Haselager, W.F.G.; Guerrero, J.E.

    2016-01-01

    The indoor localisation problem is more complex than just finding whereabouts of users. Finding positions of users relative to the devices of a smart space is even more important. Unfortunately, configuring such systems manually is a tedious process, requires expert knowledge, and is sensitive to

  8. Cutting Edge Localisation in an Edge Profile Milling Head

    NARCIS (Netherlands)

    Fernandez Robles, Laura; Azzopardi, George; Alegre, Enrique; Petkov, Nicolai

    2015-01-01

    Wear evaluation of cutting tools is a key issue for prolonging their lifetime and ensuring high quality of products. In this paper, we present a method for the effective localisation of cutting edges of inserts in digital images of an edge profile milling head. We introduce a new image data set of

  9. Application of the Localisation Platform Crowdin in Translator Education

    Science.gov (United States)

    Kudla, Dominik

    2017-01-01

    This article is an attempt to briefly describe the potential of the online localisation platform Crowdin for the education of the future translators at universities and in private courses or workshops. This description is provided on the basis of the information gathered through the user experience of the author and uses the example of the Khan…

  10. Scanning Kelvin Probe applied to localised corrosion | Haque ...

    African Journals Online (AJOL)

    This paper focuses on specific applications of the SKP system. The instrument is calibrated, using different thickness of a model polymer Poly Vinyl Butyral (PVB) on mild steel and on galvanised steel. Artificial defects are used to show how the instrument is capable of detecting a localised corrosion cell and its ability to ...

  11. Approach to sensor node calibration for efficient localisation in wireless sensor networks in realistic scenarios

    CSIR Research Space (South Africa)

    Mwila, MK

    2014-06-01

    Full Text Available Localisation or position determination is one of the most important applications for the wireless sensor networks. Numerous current techniques for localisation of sensor nodes use the Received Signal Strength Indicator (RSSI) from sensor nodes...

  12. Germ plasm localisation of the HELICc of Vasa in Drosophila: analysis of domain sufficiency and amino acids critical for localisation

    Science.gov (United States)

    Wang, Szu-Chieh; Hsu, Hao-Jen; Lin, Gee-Way; Wang, Ting-Fang; Chang, Chun-Che; Lin, Ming-Der

    2015-09-01

    Formation of the germ plasm drives germline specification in Drosophila and some other insects such as aphids. Identification of the DEAD-box protein Vasa (Vas) as a conserved germline marker in flies and aphids suggests that they share common components for assembling the germ plasm. However, to which extent the assembly order is conserved and the correlation between functions and sequences of Vas remain unclear. Ectopic expression of the pea aphid Vas (ApVas1) in Drosophila did not drive its localisation to the germ plasm, but ApVas1 with a replaced C-terminal domain (HELICc) of Drosophila Vas (DmVas) became germ-plasm restricted. We found that HELICc itself, through the interaction with Oskar (Osk), was sufficient for germ-plasm localisation. Similarly, HELICc of the grasshopper Vas could be recruited to the germ plasm in Drosophila. Nonetheless, germ-plasm localisation was not seen in the Drosophila oocytes expressing HELICcs of Vas orthologues from aphids, crickets, and mice. We further identified that glutamine (Gln) 527 within HELICc of DmVas was critical for localisation, and its corresponding residue could also be detected in grasshopper Vas yet missing in the other three species. This suggests that Gln527 is a direct target of Osk or critical to the maintenance of HELICc conformation.

  13. How AI localisation in plant tissues determines the targeted pest spectrum of different chemistries

    DEFF Research Database (Denmark)

    Buchholz, Anke; Trapp, Stefan

    penetration as first crucial step can be modified by formulation whereas the active ingredient (AI) distribution within cells is usually solely determined by physicochemical properties. This passive AI distribution was calculated with the Fick-Nernst-Planck equation implemented in a cell model....... The predictions were compared to the measured biological effects against three different arthropods. Test compounds differed in log P (-0.1 to 4.3) and pKa (4.1 to 10.7). Efficacies in different bioassays are discussed with the postulated cellular AI localisation and the individual feeding behaviour...

  14. Water Leak Localisation and Recovery in Tore Supra

    International Nuclear Information System (INIS)

    Martinez, A.; Samaille, F.; Chantant, M.; Hatchressian, J.-C.

    2006-01-01

    For almost 20 years, Tore Supra (TS) Tokamak uses water as a coolant for its plasma facing and in-vessels components. It can be considered as ITER relevant on this particular aspect. During plasma operation in TS, the water inlet temperature and outlet pressure are 120 o C and 2.4 MPa respectively, while baking is performed at 200 o C and 2 Mpa. It happened, that unexpected localized power deposits damaged in-vessels components leading to more or less large water leaks. In order to protect the vacuum vessel from over-pressurisation in case of large water leaks and to avoid the release of eventual activated materials, a pressure suppression system, composed of two rupture disks and a relief pipe header, has been designed. In the event of smaller leaks, the issue for Tore Supra operations is to apply methods capable of detecting and localising leaking water cooling circuits inside the vacuum vessel within an acceptable time. For this purpose, drainage and drying systems have been designed and manufactured to evacuate completely the water in the components and vacuum vessel, facilitating, in that way, leak testing procedure of the components. A new system allows the localization of the leaky circuit remotely by using the cooling loops monitoring system. The sub-circuits can be selected, isolated and de pressurized by the operator. Simultaneously the vacuum is monitored in the vessel and analyzed with a mass spectrometer. The water resulting from the steam condensation in the cold parts of the vacuum vessel is pumped by a new specific vacuum system in the lower parts of the machine and stored in tanks to avoid dissipation of activated products in the environment. Filters are implemented on the outlets lines of the pumps. The in-vessels components fed by the upper part of the cooling loop are connected in parallel and the water inlets and outlets are located on top of the machine, so some difficulties were encountered to drain-off completely this components. Presently

  15. Capsule-odometer: a concept to improve accurate lesion localisation.

    Science.gov (United States)

    Karargyris, Alexandros; Koulaouzidis, Anastasios

    2013-09-21

    In order to improve lesion localisation in small-bowel capsule endoscopy, a modified capsule design has been proposed incorporating localisation and - in theory - stabilization capabilities. The proposed design consists of a capsule fitted with protruding wheels attached to a spring-mechanism. This would act as a miniature odometer, leading to more accurate lesion localization information in relation to the onset of the investigation (spring expansion e.g., pyloric opening). Furthermore, this capsule could allow stabilization of the recorded video as any erratic, non-forward movement through the gut is minimised. Three-dimensional (3-D) printing technology was used to build a capsule prototype. Thereafter, miniature wheels were also 3-D printed and mounted on a spring which was attached to conventional capsule endoscopes for the purpose of this proof-of-concept experiment. In vitro and ex vivo experiments with porcine small-bowel are presented herein. Further experiments have been scheduled.

  16. Primary hepatocellular carcinoma localised by a radiolabelled monoclonal antibody

    Energy Technology Data Exchange (ETDEWEB)

    Markham, N; Ritson, A; James, O; Curtin, N; Bassendine, M; Sikora, K

    1986-01-01

    A rat monoclonal antibody, YPC2/38.8, was selected from a panel of antibodies derived by immunising rats with fresh human colorectal carcinoma. It was found to bind to a 30,000 dalton protein present on the cell surface of normal colon and liver. This protein was increased 10-fold on primary hepatocellular carcinoma (PHC) cells. After labelling with /sup 131/I, YPC2/38.8 was shown to localise human PHCs grown as xenografts in immunosuppressed mice. The authors conclude that YPC2/38.8 may have potential for diagnostic localisation and possibly thence for the selective targeting of drugs or toxins in patients with PHC arising in a liver unaffected by significant parenchymal disease. 16 refs.; 4 figs.; 1 table.

  17. La Carte de Localisation Probable des Avalanches (CPLA

    Directory of Open Access Journals (Sweden)

    Gilles BORREL

    1994-12-01

    Full Text Available La Carte de Localisation Probable des Avalanches (CPLA indique l’enveloppe des limites extrêmes connues atteintes par les avalanches, ainsi que les travaux de protection associés. Il s’agit d’un document informatif et non d’une carte de risque. Depuis 1990, les données thématiques sont numérisées.

  18. Kyste hydatique à localisation costo vertébrale

    Science.gov (United States)

    Marouf, Rachid

    2014-01-01

    L'hydatidose est une affection parasitaire due à la contamination de l'homme par la forme larvaire de ténia échinococcus granulosus, la forme costo vertébrale est une localisation très rare qui représente 0,18 à 1,21% de l'ensemble des localisations hydatiques. Nous rapportons le cas d'une femme de 32 ans qui présente un kyste hydatique multi vésiculaire à localisation costovertébrale, traité par chirurgie radicale associée à un traitement médical anti parasitaire pour une durée de 6 mois, avec bonne évolution. L'atteinte costo-vertébrale par la maladie hydatique est rare et l’évolution est insidieuse. Malgré un traitement chirurgical radical, la fréquence des récidives rend le pronostic sombre. PMID:25922632

  19. Diagnostic approach to localised organising pneumonia--A case report.

    Science.gov (United States)

    Djurić, Mirna; Považan, Djordje; Djurić, Dejan; Eri, Živka; Trudić, Anika

    2015-08-01

    Localised organising pneumonia, radiologically presented with oval or round shadows mimicing lung cancer or metastases, is a major issue in differential diagnosis. A female patient was hospitalized to clarified the etiology of multiple nodular lung lesions. The chest X-ray and the chest computed tomography (CT) revealed bilateral patchy and nodular shadows, and round lung lesions, respectively. Neither sputum analyses, nor histology of bronchoscopy samples clarified the etiology of these lung lesions. As secondary deposits in the lungs were suspected, video-assisted thoracoscopy and anterolateral right minithoracotomy with atypical upper and lower lobe resection were performed. The frozen-section analysis suggested the benign nature of the lesion, and the definite histopathological finding of localised organising pneumonia was established. Due to bilateral lung lesions, corticosteroids were applied. Seven weeks later, the chest CT finding revealed a total regression of the lesions. A surgical resection was necessary to diagnose the localised organising pneumonia which mimiced secondary malignant lesions, thus establishing the definite etiology of lung lesions. Bronchoscopic cryobiopsy, recently introduced in order to obtain peripheral lung biopsy samples, has provided new possibilities in the diagnosis and treatment of neoplastic and non-neoplastic lung diseases.

  20. Hydroxysteroid dehydrogenase HSD1L is localised to the pituitary–gonadal axis of primates

    Directory of Open Access Journals (Sweden)

    A Daniel Bird

    2017-09-01

    Full Text Available Steroid hormones play clinically important and specific regulatory roles in the development, growth, metabolism, reproduction and brain function in human. The type 1 and 2 11-beta hydroxysteroid dehydrogenase enzymes (11β-HSD1 and 2 have key roles in the pre-receptor modification of glucocorticoids allowing aldosterone regulation of blood pressure, control of systemic fluid and electrolyte homeostasis and modulation of integrated metabolism and brain function. Although the activity and function of 11β-HSDs is thought to be understood, there exists an open reading frame for a distinct 11βHSD-like gene; HSD11B1L, which is present in human, non-human primate, sheep, pig and many other higher organisms, whereas an orthologue is absent in the genomes of mouse, rat and rabbit. We have now characterised this novel HSD11B1L gene as encoded by 9 exons and analysis of EST library transcripts indicated the use of two alternate ATG start sites in exons 2 and 3, and alternate splicing in exon 9. Relatively strong HSD11B1L gene expression was detected in human, non-human primate and sheep tissue samples from the brain, ovary and testis. Analysis in non-human primates and sheep by immunohistochemistry localised HSD11B1L protein to the cytoplasm of ovarian granulosa cells, testis Leydig cells, and gonadatroph cells in the anterior pituitary. Intracellular localisation analysis in transfected human HEK293 cells showed HSD1L protein within the endoplasmic reticulum and sequence analysis suggests that similar to 11βHSD1 it is membrane bound. The endogenous substrate of this third HSD enzyme remains elusive with localisation and expression data suggesting a reproductive hormone as a likely substrate.

  1. Mps1 kinase-dependent Sgo2 centromere localisation mediates cohesin protection in mouse oocyte meiosis I.

    Science.gov (United States)

    El Yakoubi, Warif; Buffin, Eulalie; Cladière, Damien; Gryaznova, Yulia; Berenguer, Inés; Touati, Sandra A; Gómez, Rocío; Suja, José A; van Deursen, Jan M; Wassmann, Katja

    2017-09-25

    A key feature of meiosis is the step-wise removal of cohesin, the protein complex holding sister chromatids together, first from arms in meiosis I and then from the centromere region in meiosis II. Centromeric cohesin is protected by Sgo2 from Separase-mediated cleavage, in order to maintain sister chromatids together until their separation in meiosis II. Failures in step-wise cohesin removal result in aneuploid gametes, preventing the generation of healthy embryos. Here, we report that kinase activities of Bub1 and Mps1 are required for Sgo2 localisation to the centromere region. Mps1 inhibitor-treated oocytes are defective in centromeric cohesin protection, whereas oocytes devoid of Bub1 kinase activity, which cannot phosphorylate H2A at T121, are not perturbed in cohesin protection as long as Mps1 is functional. Mps1 and Bub1 kinase activities localise Sgo2 in meiosis I preferentially to the centromere and pericentromere respectively, indicating that Sgo2 at the centromere is required for protection.In meiosis I centromeric cohesin is protected by Sgo2 from Separase-mediated cleavage ensuring that sister chromatids are kept together until their separation in meiosis II. Here the authors demonstrate that Bub1 and Mps1 kinase activities are required for Sgo2 localisation to the centromere region.

  2. Plant immune and growth receptors share common signalling components but localise to distinct plasma membrane nanodomains.

    Science.gov (United States)

    Bücherl, Christoph A; Jarsch, Iris K; Schudoma, Christian; Segonzac, Cécile; Mbengue, Malick; Robatzek, Silke; MacLean, Daniel; Ott, Thomas; Zipfel, Cyril

    2017-03-06

    Cell surface receptors govern a multitude of signalling pathways in multicellular organisms. In plants, prominent examples are the receptor kinases FLS2 and BRI1, which activate immunity and steroid-mediated growth, respectively. Intriguingly, despite inducing distinct signalling outputs, both receptors employ common downstream signalling components, which exist in plasma membrane (PM)-localised protein complexes. An important question is thus how these receptor complexes maintain signalling specificity. Live-cell imaging revealed that FLS2 and BRI1 form PM nanoclusters. Using single-particle tracking we could discriminate both cluster populations and we observed spatiotemporal separation between immune and growth signalling platforms. This finding was confirmed by visualising FLS2 and BRI1 within distinct PM nanodomains marked by specific remorin proteins and differential co-localisation with the cytoskeleton. Our results thus suggest that signalling specificity between these pathways may be explained by the spatial separation of FLS2 and BRI1 with their associated signalling components within dedicated PM nanodomains.

  3. Two patients with localised hyperhidrosis of the hand based on functional and structural abnormalities of sweat glands

    DEFF Research Database (Denmark)

    Kristiansen, Bjørn H; Lindahl, Kim H; Pallesen, Kristine A U

    2018-01-01

    A 14-year-old girl and a 30-year-old woman presented with localised hyperhidrosis on the dorsal hand and wrist, respectively, provoked by different stimuli such as physical activity and minor trauma to the skin. The skin was seemingly normal in both patients where an iodine-starch test revealed...... a well-demarcated area of hyperhidrosis. Following histopathological examination, the diagnosis was unilateral localised hyperhidrosis in both cases; one with normal histology and one with a nevus sudoriferous. Both patients were successfully treated with botulinum toxin type A. The 30-year-old woman...... additionally used low-dose propantheline bromide periodically and experienced long-term remission on this therapy. Hyperhidrosis may embarrass and interfere with patients' school and careers, and it is therefore important to tailor an effective individual treatment....

  4. Orthogonal views improves localisation in bone scans of wrist

    International Nuclear Information System (INIS)

    Roth, A.L.

    1997-01-01

    Full text: Of all nuclear medicine studies, bone scans are the most fundamental. However, straightforward these may seem, there are always mechanisms that can be implemented which assist in a more precise diagnosis, particularly in areas with an intricate bone structure. An 18-year-old right-handed student presented to her doctor with a one month history of pain over the right distal radio-ulna joint area. Clinically, she had prominence of the right ulna, which suggested that there may have been a previous injury to the wrist. Also, pronation/supination were painful where there was swelling of the extensor carpi ulnaris tendon, as well as some discomfort with clicking in ulna deviation/rotation. The X-rays demonstrated some premature radial epiphysial closure. A bone scan was requested to attempt to localise the main inflammatory focus. The dynamic study was performed in the planar projection with an immediate blood pool for 300k being taken. These demonstrated a vascular blush medially. A medial blood pool image was acquired and it localised the abnormal vascularity as being dorsal. A separate focal area of less intense blood pooling was also noted in the line of the distal ulna. Delayed images showed increased uptake localised to the ulna styloid. Anatomically, the superficial vascular blush correlated with tenosynovitis. Hence, the orthogonal initial and delayed images were definitive in the diagnoses of tenosynovitis of the extensor carpi ulnaris tendon. This clearly complements the information provided by the palmar view. However, it is important to remember that an increased radiation dose to the technologist is incurred as a result of the extra orthogonal view, hence attention to technique is imperative

  5. Orthogonal views improves localisation in bone scans of wrist

    Energy Technology Data Exchange (ETDEWEB)

    Roth, A.L.

    1997-09-01

    Full text: Of all nuclear medicine studies, bone scans are the most fundamental. However, straightforward these may seem, there are always mechanisms that can be implemented which assist in a more precise diagnosis, particularly in areas with an intricate bone structure. An 18-year-old right-handed student presented to her doctor with a one month history of pain over the right distal radio-ulna joint area. Clinically, she had prominence of the right ulna, which suggested that there may have been a previous injury to the wrist. Also, pronation/supination were painful where there was swelling of the extensor carpi ulnaris tendon, as well as some discomfort with clicking in ulna deviation/rotation. The X-rays demonstrated some premature radial epiphysial closure. A bone scan was requested to attempt to localise the main inflammatory focus. The dynamic study was performed in the planar projection with an immediate blood pool for 300k being taken. These demonstrated a vascular blush medially. A medial blood pool image was acquired and it localised the abnormal vascularity as being dorsal. A separate focal area of less intense blood pooling was also noted in the line of the distal ulna. Delayed images showed increased uptake localised to the ulna styloid. Anatomically, the superficial vascular blush correlated with tenosynovitis. Hence, the orthogonal initial and delayed images were definitive in the diagnoses of tenosynovitis of the extensor carpi ulnaris tendon. This clearly complements the information provided by the palmar view. However, it is important to remember that an increased radiation dose to the technologist is incurred as a result of the extra orthogonal view, hence attention to technique is imperative.

  6. Localised corrosion in AA 2099-T83 aluminium-lithium alloy: The role of grain orientation

    International Nuclear Information System (INIS)

    Ma, Y.; Zhou, X.; Liao, Y.; Yi, Y.; Wu, H.; Wang, Z.; Huang, W.

    2016-01-01

    Highlights: • Schmid factor of the grain/subgrain can indicate its corrosion susceptibility. • The localised corrosion prefers the grain with relatively large Schmid factor. • The localised corrosion is related to selective dissolution of T_1 phase. - Abstract: The mechanism for localised corrosion in AA 2099-T83 alloy during immersion in 3.5% NaCl solution is investigated. It is found that localised corrosion tends to occur in the grain with relatively large Schmid factor. The localised corrosion is related to selective dissolution of T_1 (Al_2CuLi) phase that preferentially precipitates at grain/subgrain boundaries and dislocations within grain interiors. A model is proposed to explain the development of the localised corrosion in the alloy by taking into account heterogeneous plastic deformation during cold working and preferential precipitation of T_1 phase at crystallographic defects within deformed grains.

  7. Suppressing proton decay in theories with localised fermions

    International Nuclear Information System (INIS)

    Acharya, B.S.; Valandro, R.

    2005-12-01

    We calculate the contribution to the proton decay amplitude from Kaluza-Klein lepto-quarks in theories with extra dimensions, localised fermions and gauge fields which propagate in the bulk. Such models naturally occur within the context of M theory. In SU(5) models we show that carefully including all such modes gives a distinctive pattern of decays through various channels including a strong suppression of decays into neutrinos or right handed positrons. By contrast there is no such suppression for SO(10). (author)

  8. Anderson localisation and optical-event horizons in rogue-soliton generation.

    Science.gov (United States)

    Saleh, Mohammed F; Conti, Claudio; Biancalana, Fabio

    2017-03-06

    We unveil the relation between the linear Anderson localisation process and nonlinear modulation instability. Anderson localised modes are formed in certain temporal intervals due to the random background noise. Such localised modes seed the formation of solitary waves that will appear during the modulation instability process at those preferred intervals. Afterwards, optical-event horizon effects between dispersive waves and solitons produce an artificial collective acceleration that favours the collision of solitons, which could eventually lead to a rogue-soliton generation.

  9. Optimisation of platelet concentrates therapy: Composition, localisation, and duration of action

    Directory of Open Access Journals (Sweden)

    Yuk-Lin Yung

    2017-01-01

    Full Text Available Platelet concentrates (PC generally refers to a group of products that are prepared from autologous blood intended to enhance healing activities. PC therapy is now very popular in treating musculoskeletal injuries; however, inconsistent clinical results urge the need to understand the working mechanism of PC. It is generally believed that the platelet-derived bioactive factors are the active constituents, and their bioavailability in the vicinity of the lesion sites determines the treatment efficacies. Therefore, the composition, localisation, and duration of the action of PC would be key determinants. In this review, we discuss how different preparations and delivery methods of PC would affect the treatment outcomes with respect to clinical evidence about PC therapy for osteoarthritis, tendinopathies, rotator cuff tears, anterior cruciate ligament injuries, and bone fractures. This review can be used as a quick guide for the use of PC therapy and provide insights for the further optimisation of the therapy in the near future.

  10. Machine learning approach for single molecule localisation microscopy.

    Science.gov (United States)

    Colabrese, Silvia; Castello, Marco; Vicidomini, Giuseppe; Del Bue, Alessio

    2018-04-01

    Single molecule localisation (SML) microscopy is a fundamental tool for biological discoveries; it provides sub-diffraction spatial resolution images by detecting and localizing "all" the fluorescent molecules labeling the structure of interest. For this reason, the effective resolution of SML microscopy strictly depends on the algorithm used to detect and localize the single molecules from the series of microscopy frames. To adapt to the different imaging conditions that can occur in a SML experiment, all current localisation algorithms request, from the microscopy users, the choice of different parameters. This choice is not always easy and their wrong selection can lead to poor performance. Here we overcome this weakness with the use of machine learning. We propose a parameter-free pipeline for SML learning based on support vector machine (SVM). This strategy requires a short supervised training that consists in selecting by the user few fluorescent molecules (∼ 10-20) from the frames under analysis. The algorithm has been extensively tested on both synthetic and real acquisitions. Results are qualitatively and quantitatively consistent with the state of the art in SML microscopy and demonstrate that the introduction of machine learning can lead to a new class of algorithms competitive and conceived from the user point of view.

  11. Investigation into Generation of Micro Features by Localised Electrochemical Deposition

    Science.gov (United States)

    Debnath, Subhrajit; Laskar, Hanimur Rahaman; Bhattacharyya, B.

    2017-11-01

    With the fast advancement of technology, localised electrochemical deposition (LECD) is becoming very advantageous in generating high aspect ratio micro features to meet the steep demand in modern precision industries of the present world. Except many other advantages, this technology is highly uncomplicated and economical for fabricating metal micro-parts with in micron ranges. In the present study, copper micro-columns have been fabricated utilizing LECD process. Different process parameters such as voltage, frequency, duty ratio and electrolyte concentration, which affect the deposition performance have been identified and their effects on deposition performances such as deposition rate, height and diameter of the micro-columns have been experimentally investigated. Taguchi's methodology has been used to study the effects as well as to obtain the optimum values of process parameters so that localised deposition with best performance can be achieved. Moreover, the generated micro-columns were carefully observed under optical and scanning electron microscope from where the surface quality of the deposited micro-columns has been studied qualitatively. Also, an array of copper micro-columns has been fabricated on stainless steel (SS-304) substrate for further exploration of LECD process capability.

  12. Gliadin peptide P31-43 localises to endocytic vesicles and interferes with their maturation.

    Directory of Open Access Journals (Sweden)

    Maria Vittoria Barone

    Full Text Available BACKGROUND: Celiac Disease (CD is both a frequent disease (1:100 and an interesting model of a disease induced by food. It consists in an immunogenic reaction to wheat gluten and glutenins that has been found to arise in a specific genetic background; however, this reaction is still only partially understood. Activation of innate immunity by gliadin peptides is an important component of the early events of the disease. In particular the so-called "toxic" A-gliadin peptide P31-43 induces several pleiotropic effects including Epidermal Growth Factor Receptor (EGFR-dependent actin remodelling and proliferation in cultured cell lines and in enterocytes from CD patients. These effects are mediated by delayed EGFR degradation and prolonged EGFR activation in endocytic vesicles. In the present study we investigated the effects of gliadin peptides on the trafficking and maturation of endocytic vesicles. METHODS/PRINCIPAL FINDINGS: Both P31-43 and the control P57-68 peptide labelled with fluorochromes were found to enter CaCo-2 cells and interact with the endocytic compartment in pulse and chase, time-lapse, experiments. P31-43 was localised to vesicles carrying early endocytic markers at time points when P57-68-carrying vesicles mature into late endosomes. In time-lapse experiments the trafficking of P31-43-labelled vesicles was delayed, regardless of the cargo they were carrying. Furthermore in celiac enterocytes, from cultured duodenal biopsies, P31-43 trafficking is delayed in early endocytic vesicles. A sequence similarity search revealed that P31-43 is strikingly similar to Hrs, a key molecule regulating endocytic maturation. A-gliadin peptide P31-43 interfered with Hrs correct localisation to early endosomes as revealed by western blot and immunofluorescence microscopy. CONCLUSIONS: P31-43 and P57-68 enter cells by endocytosis. Only P31-43 localises at the endocytic membranes and delays vesicle trafficking by interfering with Hrs

  13. Intraoperative Localisation of Impalpable Breast Lesions Utilising the ROLLIS Technique Following Peritumoral 99mTc-colloid Sentinel Node Lymphoscintigraphy.

    Science.gov (United States)

    Hung, Te-Jui; Burrage, John; Bourke, Anita; Taylor, Donna

    2017-08-24

    Ultrasound or stereotactic guided hook-wire localisation has been the standard-of-care for the pre-surgical localisation of impalpable breast lesions, which account for approximately a third of all breast cancer. Radioguided occult lesion localisation using I-125 seeds (ROLLIS) is a relatively new technique for guiding surgical excision of impalpable breast lesions, and is a promising alternative to the traditional hook-wire method. When combined with Tc-99m labelled colloid for sentinel node mapping in clinically indicated cases, there has been uncertainty regarding whether the downscatter of Tc-99m into the I-125 energy spectrum could adversely affect the intra-operative detection of the I-125 seed, especially pertaining to a peritumoral injection. To evaluate the percentage contribution of downscattered activity from Tc-99m into the I-125 energy spectrum in simulated intra-operative resections of an I-125 seed following different sentinel node injection techniques. Two scenarios were simulated using breast phantoms with lean chicken breast. The first scenario, with a 2cm distance between the Tc-99m injection site and the I-125 seed, simulated a periareolar ipsiquadrant injection with the subdermal or intradermal technique. The second scenario simulated a peritumoral injection technique with the Tc-99m bolus and an I-125 seed at the same site. Count rates were acquired with a hand-held gamma probe, and the percentage contribution of downscattered Tc-99m gamma photons to the I-125 energy window was calculated. In scenarios one and two, downscattered Tc-99m activity contributed 0.5% and 33% respectively to the detected count rate in the I-125 energy window. In both scenarios, the I-125 seed was successfully localised and removed using the gamma probe. There is no significant contribution of downscattered activity associated with a peritumoral injection of Tc-99m to adversely affect the accurate intra-operative localisation of an I- 125 seed. Copyright© Bentham

  14. ErbB2-Driven Breast Cancer Cell Invasion Depends on a Complex Signaling Network Activating Myeloid Zinc Finger-1-Dependent Cathepsin B Expression

    DEFF Research Database (Denmark)

    Rafn, Bo; Nielsen, Christian Thomas Friberg; Andersen, Sofie Hagel

    2012-01-01

    Aberrant ErbB2 receptor tyrosine kinase activation in breast cancer is strongly linked to an invasive disease. The molecular basis of ErbB2-driven invasion is largely unknown. We show that cysteine cathepsins B and L are elevated in ErbB2 positive primary human breast cancer and function...... as effectors of ErbB2-induced invasion in vitro. We identify Cdc42-binding protein kinase beta, extracellular regulated kinase 2, p21-activated protein kinase 4, and protein kinase C alpha as essential mediators of ErbB2-induced cysteine cathepsin expression and breast cancer cell invasiveness. The identified...

  15. The importance of strain localisation in shear zones

    Science.gov (United States)

    Bons, Paul D.; Finch, Melanie; Gomez-Rivas, Enrique; Griera, Albert; Llorens, Maria-Gema; Steinbach, Florian; Weikusat, Ilka

    2016-04-01

    The occurrence of various types of shear bands (C, C', C'') in shear zones indicate that heterogeneity of strain is common in strongly deformed rocks. However, the importance of strain localisation is difficult to ascertain if suitable strain markers are lacking, which is usually the case. Numerical modelling with the finite-element method has so far not given much insight in the development of shear bands. We suggest that this is not only because the modelled strains are often not high enough, but also because this technique (that usually assumes isotropic material properties within elements) does not properly incorporate mineral deformation behaviour. We simulated high-strain, simple-shear deformation in single- and polyphase materials with a full-field theory (FFT) model coupled to the Elle modelling platform (www.elle.ws; Lebensohn 2001; Bons et al. 2008). The FFT-approach simulates visco-plastic deformation by dislocation glide, taking into account the different available slip systems and their critical resolved shear stresses in relations to the applied stresses. Griera et al. (2011; 2013) have shown that this approach is particularly well suited for strongly anisotropic minerals, such as mica and ice Ih (Llorens 2015). We modelled single- and polyphase composites of minerals with different anisotropies and strengths, roughly equivalent to minerals such as ice Ih, mica, quartz and feldspar. Single-phase polycrystalline aggregates show distinct heterogeneity of strain rate, especially in case of ice Ih, which is mechanically close to mica (see also Griera et al. 2015). Finite strain distributions are heterogeneous as well, but the patterns may differ from that of the strain rate distribution. Dynamic recrystallisation, however, usually masks any strain and strain rate localisation (Llorens 2015). In case of polyphase aggregates, equivalent to e.g. a granite, we observe extensive localisation in both syn- and antithetic shear bands. The antithetic shear bands

  16. Evaluating ALWadHA for providing secure localisation for wireless sensor networks

    CSIR Research Space (South Africa)

    Abu-Mahfouz, Adnan M

    2013-09-01

    Full Text Available secure localisation algorithms that are able to work in a hostile environment. An attacker could compromise, or masquerade as, a beacon node and send incorrect location information. Localisation in a hostile environment is a critical problem in wireless...

  17. Neuroglobin in the rat brain (II): co-localisation with neurotransmitters

    DEFF Research Database (Denmark)

    Hundahl, Christian Ansgar; Kelsen, Jesper; Dewilde, Sylvia

    2008-01-01

    In an accompanying article, we found that neuroglobin (Ngb) was expressed in a few well-defined nuclei in the rat brain. Here, we show by use of immunohistochemistry and in situ hybridisation (ISH) that Ngb co-localise with several specific neurotransmitters. Ngb co-localise consistently with tyr...

  18. The Drosophila cell adhesion molecule Neuroglian regulates Lissencephaly-1 localisation in circulating immunosurveillance cells

    Directory of Open Access Journals (Sweden)

    Williams Michael J

    2009-03-01

    Full Text Available Abstract Background When the parasitoid wasp Leptopilina boulardi lays its eggs in Drosophila larvae phagocytic cells called plasmatocytes and specialized cells known as lamellocytes encapsulate the egg. This requires these circulating immunosurveillance cells (haemocytes to change from a non-adhesive to an adhesive state enabling them to bind to the invader. Interestingly, attachment of leukocytes, platelets, and insect haemocytes requires the same adhesion complexes as epithelial and neuronal cells. Results Here evidence is presented showing that the Drosophila L1-type cell adhesion molecule Neuroglian (Nrg is required for haemocytes to encapsulate L. boulardi wasp eggs. The amino acid sequence FIGQY containing a conserved phosphorylated tyrosine is found in the intracellular domain of all L1-type cell adhesion molecules. This conserved tyrosine is phosphorylated at the cell periphery of plasmatocytes and lamellocytes prior to parasitisation, but dephosphorylated after immune activation. Intriguingly, another pool of Nrg located near the nucleus of plasmatocytes remains phosphorylated after parasitisation. In mammalian neuronal cells phosphorylated neurofascin, another L1-type cell adhesion molecule interacts with a nucleokinesis complex containing the microtubule binding protein lissencephaly-1 (Lis1 1. Interestingly in plasmatocytes from Nrg mutants the nucleokinesis regulating protein Lissencephaly-1 (Lis1 fails to localise properly around the nucleus and is instead found diffuse throughout the cytoplasm and at unidentified perinuclear structures. After attaching to the wasp egg control plasmatocytes extend filopodia laterally from their cell periphery; as well as extending lateral filopodia plasmatocytes from Nrg mutants also extend many filopodia from their apical surface. Conclusion The Drosophila cellular adhesion molecule Neuroglian is expressed in haemocytes and its activity is required for the encapsulation of L. boularli eggs. At

  19. Dark matter and localised fermions from spherical orbifolds?

    Energy Technology Data Exchange (ETDEWEB)

    Cacciapaglia, Giacomo; Deandrea, Aldo [Université de Lyon,Lyon (France); Université Lyon 1, CNRS/IN2P3, UMR5822 IPNL,F-69622 Villeurbanne Cedex (France); Deutschmann, Nicolas [Université de Lyon,Lyon (France); Université Lyon 1, CNRS/IN2P3, UMR5822 IPNL,F-69622 Villeurbanne Cedex (France); Centre for Cosmology, Particle Physics and Phenomenology (CP3),Université catholique de Louvain,Chemin du Cyclotron 2, B-1348 Louvain-la-Neuve (Belgium)

    2016-04-14

    We study a class of six-dimensional models based on positive curvature surfaces (spherical 2-orbifolds) as extra-spaces. Using the Newman-Penrose formalism, we discuss the particle spectrum in this class of models. The fermion spectrum problem, which has been addressed with flux compactifications in the past, can be avoided using localised fermions. In this framework, we find that there are four types of geometry compatible with the existence of a stable dark matter candidate and we study the simplest case in detail. Using the complementarity between collider resonance searches and relic density constraints, we show that this class of models is under tension, unless the model lies in a funnel region characterised by a resonant Higgs s-channel in the dark matter annihilation.

  20. Østebø, Terje. — Localising Salafism

    OpenAIRE

    Vezzadini, Elena

    2012-01-01

    Localising Salafism est une étude approfondie sur l’origine et le développement du salafisme dans le Bale, une province au sud-est de l’Éthiopie, habitée majoritairement par les Oromo qui y constituent environ 90 % de la population. il s’agit aussi d’une région à grande majorité musulmane (92 %), qui fait partie des neuf divisions administratives de l’Éthiopie, connue comme Oromiyaa. L’auteur travaille donc sur une région très peu étudiée, et sur un sujet, l’islam en Éthiopie, encore marginal...

  1. Globally reasoning about localised security policies in distributed systems

    DEFF Research Database (Denmark)

    Hernandez, Alejandro Mario

    In this report, we aim at establishing proper ways for model checking the global security of distributed systems, which are designed consisting of set of localised security policies that enforce specific issues about the security expected. The systems are formally specified following a syntax......, defined in detail in this report, and their behaviour is clearly established by the Semantics, also defined in detail in this report. The systems include the formal attachment of security policies into their locations, whose intended interactions are trapped by the policies, aiming at taking access...... control decisions of the system, and the Semantics also takes care of this. Using the Semantics, a Labelled Transition System (LTS) can be induced for every particular system, and over this LTS some model checking tasks could be done. We identify how this LTS is indeed obtained, and propose an alternative...

  2. 3D Image Fusion to Localise Intercostal Arteries During TEVAR

    Directory of Open Access Journals (Sweden)

    G. Koutouzi

    Full Text Available Purpose: Preservation of intercostal arteries during thoracic aortic procedures reduces the risk of post-operative paraparesis. The origins of the intercostal arteries are visible on pre-operative computed tomography angiography (CTA, but rarely on intra-operative angiography. The purpose of this report is to suggest an image fusion technique for intra-operative localisation of the intercostal arteries during thoracic endovascular repair (TEVAR. Technique: The ostia of the intercostal arteries are identified and manually marked with rings on the pre-operative CTA. The optimal distal landing site in the descending aorta is determined and marked, allowing enough length for an adequate seal and attachment without covering more intercostal arteries than necessary. After 3D/3D fusion of the pre-operative CTA with an intra-operative cone-beam CT (CBCT, the markings are overlaid on the live fluoroscopy screen for guidance. The accuracy of the overlay is confirmed with digital subtraction angiography (DSA and the overlay is adjusted when needed. Stent graft deployment is guided by the markings. The initial experience of this technique in seven patients is presented. Results: 3D image fusion was feasible in all cases. Follow-up CTA after 1 month revealed that all intercostal arteries planned for preservation, were patent. None of the patients developed signs of spinal cord ischaemia. Conclusion: 3D image fusion can be used to localise the intercostal arteries during TEVAR. This may preserve some intercostal arteries and reduce the risk of post-operative spinal cord ischaemia. Keywords: TEVAR, Intercostal artery, Spinal cord ischaemia, 3D image fusion, Image guidance, Cone-beam CT

  3. Localisation and mechanism of renal retention of radiolabelled somatostatin analogues

    Energy Technology Data Exchange (ETDEWEB)

    Melis, Marleen; Krenning, Eric P.; Bernard, Bert F.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Barone, Raffaella [UCL, Centre of Nuclear Medicine and Laboratory of PET, Brussels (Belgium); Visser, Theo J. [Erasmus MC, Department of Internal Medicine, Rotterdam (Netherlands)

    2005-10-01

    Radiolabelled somatostatin analogues, such as octreotide and octreotate, are used for tumour scintigraphy and radionuclide therapy. The kidney is the most important critical organ during such therapy owing to the reabsorption and retention of radiolabelled peptides. The aim of this study was to investigate in a rat model both the localisation and the mechanism of renal uptake after intravenous injection of radiolabelled somatostatin analogues. The multi-ligand megalin/cubilin receptor complex, responsible for reabsorption of many peptides and proteins in the kidney, is an interesting candidate for renal endocytosis of these peptide analogues. For localisation studies, ex vivo autoradiography and micro-autoradiography of rat kidneys were performed 1-24 h after injection of radiolabelled somatostatin analogues and compared with the renal anti-megalin immunohistochemical staining pattern. To confirm a role of megalin in the mechanism of renal retention of [{sup 111}In-DTPA]octreotide, the effects of three inhibitory substances were explored in rats. Renal ex vivo autoradiography showed high cortical radioactivity and lower radioactivity in the outer medulla. The distribution of cortical radioactivity was inhomogeneous. Micro-autoradiography indicated that radioactivity was only retained in the proximal tubules. The anti-megalin immunohistochemical staining pattern showed a strong similarity with the renal [{sup 111}In-DTPA]octreotide ex vivo autoradiograms. Biodistribution studies showed that co-injection of positively charged d-lysine reduced renal uptake to 60% of control. Sodium maleate reduced renal [{sup 111}In-DTPA]octreotide uptake to 15% of control. Finally, cisplatin pre-treatment of rats reduced kidney uptake to 70% of control. Renal retention of [{sup 111}In-DTPA]octreotide is confined to proximal tubules in the rat kidney, in which megalin-mediated endocytosis may play an important part. (orig.)

  4. Feasibility of magnetic marker localisation for non-palpable breast cancer.

    Science.gov (United States)

    Schermers, B; van der Hage, J A; Loo, C E; Vrancken Peeters, M T F D; Winter-Warnars, H A O; van Duijnhoven, F; Ten Haken, B; Muller, S H; Ruers, T J M

    2017-06-01

    Accurate tumour localisation is essential for breast-conserving surgery of non-palpable tumours. Current localisation technologies are associated with disadvantages such as logistical challenges and migration issues (wire guided localisation) or legislative complexities and high administrative burden (radioactive localisation). We present MAgnetic MArker LOCalisation (MaMaLoc), a novel technology that aims to overcome these disadvantages using a magnetic marker and a magnetic detection probe. This feasibility study reports on the first experience with this new technology for breast cancer localisation. Fifteen patients with unifocal, non-palpable breast cancer were recruited. They received concurrent placement of the magnetic marker in addition to a radioactive iodine seed, which is standard of care in our clinic. In a subset of five patients, migration of the magnetic marker was studied. During surgery, a magnetic probe and gammaprobe were alternately used to localise the markers and guide surgery. The primary outcome parameter was successful transcutaneous identification of the magnetic marker. Additionally, data on radiologist and surgeon satisfaction were collected. Magnetic marker placement was successful in all cases. Radiologists could easily adapt to the technology in the clinical workflow. Migration of the magnetic marker was negligible. The primary endpoint of the study was met with an identification rate of 100%. Both radiologists and surgeons reflected that the technology was intuitive to use and that it was comparable to radioactive iodine seed localisation. Magnetic marker localisation for non-palpable breast cancer is feasible and safe, and may be a viable non-radioactive alternative to current localisation technologies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Rho GTPase activity modulates paramyxovirus fusion protein-mediated cell-cell fusion

    International Nuclear Information System (INIS)

    Schowalter, Rachel M.; Wurth, Mark A.; Aguilar, Hector C.; Lee, Benhur; Moncman, Carole L.; McCann, Richard O.; Dutch, Rebecca Ellis

    2006-01-01

    The paramyxovirus fusion protein (F) promotes fusion of the viral envelope with the plasma membrane of target cells as well as cell-cell fusion. The plasma membrane is closely associated with the actin cytoskeleton, but the role of actin dynamics in paramyxovirus F-mediated membrane fusion is unclear. We examined cell-cell fusion promoted by two different paramyxovirus F proteins in three cell types in the presence of constitutively active Rho family GTPases, major cellular coordinators of actin dynamics. Reporter gene and syncytia assays demonstrated that expression of either Rac1 V12 or Cdc42 V12 could increase cell-cell fusion promoted by the Hendra or SV5 glycoproteins, though the effect was dependent on the cell type expressing the viral glycoproteins. In contrast, RhoA L63 decreased cell-cell fusion promoted by Hendra glycoproteins but had little affect on SV5 F-mediated fusion. Also, data suggested that GTPase activation in the viral glycoprotein-containing cell was primarily responsible for changes in fusion. Additionally, we found that activated Cdc42 promoted nuclear rearrangement in syncytia

  6. Ablation of p120-Catenin Altering the Activity of Small GTPase in Human Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Nan LIU

    2009-05-01

    Full Text Available Background and objective p120-catenin (p120ctn, a member of the Armadillo gene family, has emerged as an important modulator of small GTPase activities. Therefore, it plays novel roles in tumor malignant phenotype, such as invasion and metastasis, whose mechanism are not well clarified yet. The aim of this study is to explore the roles of p120ctn on the regulation of small GTP family members in lung cancer and the effects to lung cancer invasions andmetastasis. Methods After p120ctn was knocked down by siRNA, in vivo and in vitro analysis was applied to investigate the role and possible mechanism of p120ctn in lung cancer, such as Western Blot, pull-down analysis, and nude mice models. Results p120ctn depletion inactivated RhoA, with the the activity of Cdc42 and Rac1 increased, the invasiveness of lung cancer cells was promoted both in vitro and in vivo . Conclusion p120ctn gene knockdown enhances the metastasis of lung cancer cells, probably by altering expression of small GTPase, such as inactivation of RhoA and activation of Cdc42/Rac1.

  7. Radio-guided occult lesion localisation using iodine-125 seeds ('ROLLIS') for removal of impalpable breast lesions: first Australian experience

    International Nuclear Information System (INIS)

    Taylor, Donna B.; Bourke, Anita G.; Westcott, Eliza

    2015-01-01

    Approximately one-third of breast cancers are impalpable and require pre-operative image-guided localisation. Hook-wire localisation (HWL) is commonly used but has several disadvantages. Use of a low-activity radioactive iodine-125 seed is a promising alternative technique used in the USA and the Netherlands. This pilot study describes the first use of this in Australia. In this prospective pilot study, 21 participants with biopsy-proven breast cancer underwent radio guided occult lesion localisation using iodine-125 seed(s) (ROLLIS) with insertion of a hook-wire for back up. Sentinel node biopsy was performed where indicated. Ease of hook-wire and seed insertion, duration of the procedure, dependence on the seed versus hook-wire during surgery, lesion location within the specimen, histopathology including size of radial margins, the ease of seed retrieval in pathology, and safe return of seeds for disposal were documented. Radiation dosimetry of staff was performed. All seeds were placed within 3.5 mm of the lesion. All lesions and seeds were removed. One participant needed re-excision for involved margins. Radiologists and surgeons both preferred ROLLIS. Surgeons were able to depend on the seed for localisation in all but one case. Sentinel node biopsy was successfully performed when required. Pathologists found seed retrieval quick and easy, with no detrimental effect on tissue processing. No radiation doses measurably above background were received by staff. ROLLIS is an easily learnt, safe and effective alternative technique to standard HWL.

  8. Prognostic Biomarkers Used for Localised Prostate Cancer Management: A Systematic Review.

    Science.gov (United States)

    Lamy, Pierre-Jean; Allory, Yves; Gauchez, Anne-Sophie; Asselain, Bernard; Beuzeboc, Philippe; de Cremoux, Patricia; Fontugne, Jacqueline; Georges, Agnès; Hennequin, Christophe; Lehmann-Che, Jacqueline; Massard, Christophe; Millet, Ingrid; Murez, Thibaut; Schlageter, Marie-Hélène; Rouvière, Olivier; Kassab-Chahmi, Diana; Rozet, François; Descotes, Jean-Luc; Rébillard, Xavier

    2017-03-07

    Prostate cancer stratification is based on tumour size, pretreatment PSA level, and Gleason score, but it remains imperfect. Current research focuses on the discovery and validation of novel prognostic biomarkers to improve the identification of patients at risk of aggressive cancer or of tumour relapse. This systematic review by the Intergroupe Coopérateur Francophone de Recherche en Onco-urologie (ICFuro) analysed new evidence on the analytical validity and clinical validity and utility of six prognostic biomarkers (PHI, 4Kscore, MiPS, GPS, Prolaris, Decipher). All available data for the six biomarkers published between January 2002 and April 2015 were systematically searched and reviewed. The main endpoints were aggressive prostate cancer prediction, additional value compared to classical prognostic parameters, and clinical benefit for patients with localised prostate cancer. The preanalytical and analytical validations were heterogeneous for all tests and often not adequate for the molecular signatures. Each biomarker was studied for specific indications (candidates for a first or second biopsy, and potential candidates for active surveillance, radical prostatectomy, or adjuvant treatment) for which the level of evidence (LOE) was variable. PHI and 4Kscore were the biomarkers with the highest LOE for discriminating aggressive and indolent tumours in different indications. Blood biomarkers (PHI and 4Kscore) have the highest LOE for the prediction of more aggressive prostate cancer and could help clinicians to manage patients with localised prostate cancer. The other biomarkers show a potential prognostic value; however, they should be evaluated in additional studies to confirm their clinical validity. We reviewed studies assessing the value of six prognostic biomarkers for prostate cancer. On the basis of the available evidence, some biomarkers could help in discriminating between aggressive and non-aggressive tumours with an additional value compared to the

  9. Colonoscopy and computerised tomography scan are not sufficient to localise right sided colonic lesions accurately.

    LENUS (Irish Health Repository)

    Solon, Jacqueline Gemma

    2009-11-23

    : Aim: accurate pre-operative localisation of colonic lesions is critical especially in laparoscopic colectomy where tactile localisation is absent particularly in screen-detected tumours. The study aimed to evaluate the accuracy of colonoscopy and double-contrast computerised tomography (CT) to localise lesions treated by right hemicolectomy. Method: a retrospective chart review was performed of patients treated by right hemicolectomy under the colorectal service between July 2003 and October 2006. Pre-operative tumour location determined by CT scan and colonoscopy were compared with the intra-operative and histopathologic findings. Results: of 101 patients, 73 (73%) were for adenoma or cancer, with a final diagnosis of adenocarcinoma in 59 (59%). Pre-operative localisation was inaccurate in 29% of lesions using both CT and colonoscopy. In the transverse colon colonoscopy alone was only 37.5% accurate, increasing to 62.5% when information from the CT scan was added. Conclusion: pre-operative localisation of right-sided colon cancers using colonoscopy and CT scanning is unreliable in at least 29% of cases. Inaccurate localisation of transverse colon tumours risks inadequate lymphadenectomy with an adverse cancer outcome. Pre-operative abdominal CT scan improves accuracy but endoscopic tattoo localisation should be employed routinely especially in patients undergoing laparoscopic resection.

  10. Localised boundary air layer and clothing evaporative resistances for individual body segments.

    Science.gov (United States)

    Wang, Faming; del Ferraro, Simona; Lin, Li-Yen; Sotto Mayor, Tiago; Molinaro, Vincenzo; Ribeiro, Miguel; Gao, Chuansi; Kuklane, Kalev; Holmér, Ingvar

    2012-01-01

    Evaporative resistance is an important parameter to characterise clothing thermal comfort. However, previous work has focused mainly on either total static or dynamic evaporative resistance. There is a lack of investigation of localised clothing evaporative resistance. The objective of this study was to study localised evaporative resistance using sweating thermal manikins. The individual and interaction effects of air and body movements on localised resultant evaporative resistance were examined in a strict protocol. The boundary air layer's localised evaporative resistance was investigated on nude sweating manikins at three different air velocity levels (0.18, 0.48 and 0.78 m/s) and three different walking speeds (0, 0.96 and 1.17 m/s). Similarly, localised clothing evaporative resistance was measured on sweating manikins at three different air velocities (0.13, 0.48 and 0.70 m/s) and three walking speeds (0, 0.96 and 1.17 m/s). Results showed that the wind speed has distinct effects on local body segments. In contrast, walking speed brought much more effect on the limbs, such as thigh and forearm, than on body torso, such as back and waist. In addition, the combined effect of body and air movement on localised evaporative resistance demonstrated that the walking effect has more influence on the extremities than on the torso. Therefore, localised evaporative resistance values should be provided when reporting test results in order to clearly describe clothing local moisture transfer characteristics. Localised boundary air layer and clothing evaporative resistances are essential data for clothing design and assessment of thermal comfort. A comprehensive understanding of the effects of air and body movement on localised evaporative resistance is also necessary by both textile and apparel researchers and industry.

  11. Optimal localisation of next generation Biofuel production in Sweden

    Energy Technology Data Exchange (ETDEWEB)

    Wetterlund, Elisabeth [Linkoeping Univ., Linkoeping (Sweden); Pettersson, Karin [Chalmers Univ. of Technology, Goeteborg (Sweden); Mossberg, Johanna [SP Technical Research Inst. of Sweden, Boraas (Sweden)] [and others

    2013-09-01

    With a high availability of lignocellulosic biomass and various types of cellulosic by-products, as well as a large number of industries, Sweden is a country of great interest for future large scale production of sustainable, next generation biofuels. This is most likely also a necessity as Sweden has the ambition to be independent of fossil fuels in the transport sector by the year 2030 and completely fossil free by 2050. In order to reach competitive biofuel production costs, plants with large production capacities are likely to be required. Feedstock intake capacities in the range of about 1-2 million tonnes per year, corresponding to a biomass feed of 300-600 MW, can be expected, which may lead to major logistical challenges. To enable expansion of biofuel production in such large plants, as well as provide for associated distribution requirements, it is clear that substantial infrastructure planning will be needed. The geographical location of the production plant facilities is therefore of crucial importance and must be strategic to minimise the transports of raw material as well as of final product. Competition for the available feedstock, from for example forest industries and CHP plants (combined heat and power) further complicates the localisation problem. Since the potential for an increased biomass utilisation is limited, high overall resource efficiency is of great importance. Integration of biofuel production processes in existing industries or in district heating systems may be beneficial from several aspects, such as opportunities for efficient heat integration, feedstock and equipment integration, as well as access to existing experience and know-how. This report describes the development of Be Where Sweden, a geographically explicit optimisation model for localisation of next generation biofuel production plants in Sweden. The main objective of developing such a model is to be able to assess production plant locations that are robust to varying

  12. Radioguided localisation of impalpable breast lesions using 99m-Technetium macroaggregated albumin: Lessons learnt during introduction of a new technique to guide preoperative localisation

    Energy Technology Data Exchange (ETDEWEB)

    Landman, Joanne [Department of Nuclear Medicine, Royal Perth Hospital, Perth, Western Australia (Australia); Kulawansa, Sagarika [Department of Diagnostic and Interventional Radiology, Royal Perth Hospital, Perth, Western Australia (Australia); McCarthy, Michael; Troedson, Russell [Department of Nuclear Medicine, Royal Perth Hospital, Perth, Western Australia (Australia); Phillips, Michael [Western Australian Institute for Medical Research, University of Western Australia, Perth, Western Australia (Australia); Tinning, Jill [The Multidisciplinary Breast Service, Royal Perth Hospital, Perth, Western Australia (Australia); Taylor, Donna, E-mail: Donna.Taylor@health.wa.gov.au [Department of Diagnostic and Interventional Radiology, Royal Perth Hospital, Perth, Western Australia (Australia); School of Surgery, University of Western Australia, Perth, Western Australia (Australia); Department of Nuclear Medicine, Royal Perth Hospital, Perth, Western Australia (Australia)

    2015-03-15

    Preoperative wire-guided localisation (WGL) of impalpable breast lesions is widely used but can be technically difficult. Risks include wire migration, inaccurate placement, and inadequate surgical margins. Research shows that radioguided occult lesion localisation (ROLL) is quicker, easier, and can improve surgical and cosmetic outcomes. An audited introduction of ROLL was conducted to validate the technique as a feasible alternative to WGL. Fifty patients with single impalpable lesions and biopsy proven malignancy or indeterminate histology underwent WGL followed by intralesional radiopharmaceutical injection of 99m-Technetium macroaggregated albumin. Postprocedural mammography was performed to demonstrate wire position, and scintigraphy to evaluate radiopharmaceutical migration. Lymphoscintigraphy and intraoperative sentinel node biopsy were performed if indicated, followed by lesion localisation and excision using a gamma probe. Specimen imaging was performed, with immediate reexcision for visibly inadequate margins. Accurate localisation was achieved in 86% of patients with ROLL compared to 72% with WGL. All lesions were successfully removed, with clear margins in 71.8% of malignant lesions. Reexcision and intraoperative sentinel node localisation rates were equivalent to preaudit figures for WGL. ROLL was easy to perform and problems were infrequent. Inaccurate radiopharmaceutical placement necessitating WGL occurred in four patients. Minor radiopharmaceutical migration was common, but precluded using ROLL in only two cases. ROLL is effective, simple, inexpensive, and easily learnt; however, preoperative confirmation of correct radiopharmaceutical placement using mammography and the gamma probe is important to help ensure successful lesion removal. Insertion of a backup hookwire is recommended during the initial introduction of ROLL.

  13. Localisation and identification of radioactive particles in solid samples by means of a nuclear track technique

    International Nuclear Information System (INIS)

    Boehnke, Antje; Treutler, Hanns-Christian; Freyer, Klaus; Schubert, Michael; Holger Weiss

    2005-01-01

    This study is aimed to develop a generally applicable methodology of investigation that can be used for the localisation of single alpha-active particles in solid samples, such as industrial dust or natural soils, sediments and rocks by autoradiography using solid-state nuclear track detectors. The developed technique allows the detection of local enrichments of alpha-emitters in any solid material. The results of such an investigation are of interest from technical, biological and environmental points of view. The idea behind the methodology is to locate the position of alpha-active spots in a sample by attaching the track detector to the sample in a defined manner, thoroughly described in the paper. The located alpha-active particles are subsequently analysed by an electron microscope and an electron microprobe. An example of the application of this methodology is also given. An ultra-fine -grained ore-processing residue, which causes serious environmental pollution in the respective mining district and thus limits possible land use and affects quality of life in the area, was examined using the described technique. The investigation revealed considerable amounts of alpha-active particles in this material

  14. Effect of season on peripheral resistance to localised cold stress

    Science.gov (United States)

    Tanaka, M.; Harimura, Y.; Tochihara, Y.; Yamazaki, S.; Ohnaka, T.; Matsui, J.; Yoshida, K.

    1984-03-01

    This study was carried out to determine the effect that seasonal changes have on the effect of localised cold stress on peripheral temperatures using the foot immersion method with a cold water bath. The subjects were six males and four females. The data were obtained in April, July, October and January. Skin temperature of the right index finger, the forehead, the arm, the cheek, the second toe and the instep were measured before, during and after the immersion of the feet in water at 15°C for 10 mins, as well as oxygen consumption before immersion of the feet. The average finger temperature was highest during foot immersion in the summer, next highest in the winter, then spring, and the lowest during foot immersion in the autumn. The finger temperatures during the pre-immersion period in the autumn tended to be lower than in other seasons. The finger temperatures during the pre-immersion period affected the temperature change of the finger during the immersion period. The rate of increase of the toe temperature and the foot temperature during post-immersion in the summer and the spring were greater than those in the autumn and winter. Oxygen consumption during the pre-immersion period in the autumn was significantly lower than in the other seasons (pCooling the feet caused no significant changes in the temperatures the cheek, forehead or forearm. The cheek temperature in the summer and autumn was cooler than corresponding temperatures taken in the winter and spring.

  15. The Competition Between a Localised and Distributed Source of Buoyancy

    Science.gov (United States)

    Partridge, Jamie; Linden, Paul

    2012-11-01

    We propose a new mathematical model to study the competition between localised and distributed sources of buoyancy within a naturally ventilated filling box. The main controlling parameters in this configuration are the buoyancy fluxes of the distributed and local source, specifically their ratio Ψ. The steady state dynamics of the flow are heavily dependent on this parameter. For large Ψ, where the distributed source dominates, we find the space becomes well mixed as expected if driven by an distributed source alone. Conversely, for small Ψ we find the space reaches a stable two layer stratification. This is analogous to the classical case of a purely local source but here the lower layer is buoyant compared to the ambient, due to the constant flux of buoyancy emanating from the distributed source. The ventilation flow rate, buoyancy of the layers and also the location of the interface height, which separates the two layer stratification, are obtainable from the model. To validate the theoretical model, small scale laboratory experiments were carried out. Water was used as the working medium with buoyancy being driven directly by temperature differences. Theoretical results were compared with experimental data and overall good agreement was found. A CASE award project with Arup.

  16. Le kyste hydatique du cordon spermatique: une localisation exceptionnelle

    Science.gov (United States)

    Hamdane, Mohamed Moncef; Bougrine, Fethi; Msakni, Issam; Dhaoui-Ghozzi, Amen; Bouziani, Ammar

    2011-01-01

    L’ hydatidose est une anthropo-zoonose due au développement chez l'homme de la forme larvaire du taenia Echinococcus granulosis. La plupart des kystes hydatiques se localisent dans le foie et les poumons. Le kyste hydatique du cordon spermatique est extrêmement rare avec seulement 4 cas rapportés dans la littérature. Les auteurs rapportent dans cet article un nouveau cas d'hydatidose du cordon spermatique. Il s'agissait d'un homme de 40 ans qui consultait pour des douleurs scrotales évoluant depuis huit mois. L'examen clinique a mis en évidence une tuméfaction mobile, inguino-scrotale, droite. L’échographie testiculaire a objectivé une hernie inguinale droite associée à deux kystes épididymaires bilatéraux. Le patient a été opéré pour cure de son hernie avec découverte en per-opératoire d'un kyste du cordon spermatique qui a été réséqué. L'examen anatomopathologique a conclu à une hydatidose du cordon spermatique. PMID:22384304

  17. The instability of internal gravity waves to localised disturbances

    Directory of Open Access Journals (Sweden)

    J. Vanneste

    1995-02-01

    Full Text Available The instability of an internal gravity wave due to nonlinear wave-wave interaction is studied theoretically and numerically. Three different aspects of this phenomenon are examined. 1. The influence of dissipation on both the resonant and the nonresonant interactions is analysed using a normal mode expansion of the basic equations. In particular, the modifications induced in the interaction domain are calculated and as a result some modes are shown to be destabilised by dissipation. 2. The evolution of an initial unstable disturbance of finite vertical extent is described as the growth of two secondary wave packets travelling at the same group velocity. A quasi-linear correction to the basic primary wave is calculated, corresponding to a localised amplitude decrease due to the disturbance growth. 3. Numerical experiments are carried out to study the effect of a basic shear on wave instability. It appears that the growing secondary waves can have a frequency larger than that of the primary wave, provided that the shear is sufficient. The instability of waves with large amplitude and long period, such as tides or planetary waves, could therefore be invoked as a possible mechanism for the generation of gravity waves with shorter period in the middle atmosphere.

  18. An insect-inspired bionic sensor for tactile localisation and material classification with state-dependent modulation

    Directory of Open Access Journals (Sweden)

    Luca ePatanè

    2012-08-01

    Full Text Available Insects carry a pair of antennae on their head: multimodal sensory organs that serve a wide range of sensory-guided behaviours. During locomotion, antennae are involved in near-range orientation, for example in detecting, localising, probing and negotiating obstacles.Here we present a bionic, active tactile sensing system inspired by insect antennae. It comprises an actuated elastic rod equipped with a terminal acceleration sensor. The measurement principle is based on the analysis of damped harmonic oscillations registered upon contact with an object. The dominant frequency of the oscillation is extracted to determine the distance of the contact point along the probe, and basal angular encoders allow tactile localisation in a polar coordinate system. Finally, the damping behaviour of the registered signal is exploited to determine the most likely material.The tactile sensor is tested in four approaches with increasing neural plausibility: First, we show that peak extraction from the Fourier spectrum is sufficient for tactile localisation with position errors below 1%. Also, the damping property of the extracted frequency is used for material classification. Second, we show that the Fourier spectrum can be analysed by an Artificial Neural Network which can be trained to decode contact distance and to classify contact materials. Thirdly, we show how efficiency can be improved by band-pass filtering the Fourier spectrum by application of non-negative matrix factorisation. This reduces the input dimension by 95% while reducing classification performance by 8% only. Finally, we replace the FFT by an array of spiking neurons with gradually differing resonance properties, such that their spike rate is a function of the input frequency. We show that this network can be applied to detect tactile contact events of a wheeled robot, and how detrimental effects of robot velocity on antennal dynamics can be suppressed by state-dependent modulation of the

  19. An Efficient Approach for Node Localisation and Tracking in Wireless Sensor Networks

    CSIR Research Space (South Africa)

    Mwila, Martin

    2014-08-01

    Full Text Available -1 An Efficient Approach for Node Localisation and Tracking in Wireless Sensor Networks Martin K. Mwila Submitted in partial fulfilment of the requirements for the degree Magister Technologiae: Electrical Engineering in the Department of Electrical Engineering...

  20. An efficient distributed localisation algorithm for wireless sensor networks: based on smart reference-selection method

    CSIR Research Space (South Africa)

    Abu-Mahfouz, Adnan M

    2013-05-01

    Full Text Available Determining the location of nodes is a key part of wireless sensor networks (WSNs). Many WSN applications require knowledge of nodes’ locations to perform their functions successfully. Several localisation algorithms rely on using all or most...

  1. Electron localisation in static and time-dependent one-dimensional model systems

    Science.gov (United States)

    Durrant, T. R.; Hodgson, M. J. P.; Ramsden, J. D.; Godby, R. W.

    2018-02-01

    The most direct signature of electron localisation is the tendency of an electron in a many-body system to exclude other same-spin electrons from its vicinity. By applying this concept directly to the exact many-body wavefunction, we find that localisation can vary considerably between different ground-state systems, and can also be strongly disrupted, as a function of time, when a system is driven by an applied electric field. We use this measure to assess the well-known electron localisation function (ELF), both in its approximate single-particle form (often applied within density-functional theory) and its full many-particle form. The full ELF always gives an excellent description of localisation, but the approximate ELF fails in time-dependent situations, even when the exact Kohn-Sham orbitals are employed.

  2. Leakage localisation method in a water distribution system based on sensitivity matrix: methodology and real test

    OpenAIRE

    Pascual Pañach, Josep

    2010-01-01

    Leaks are present in all water distribution systems. In this paper a method for leakage detection and localisation is presented. It uses pressure measurements and simulation models. Leakage localisation methodology is based on pressure sensitivity matrix. Sensitivity is normalised and binarised using a common threshold for all nodes, so a signatures matrix is obtained. A pressure sensor optimal distribution methodology is developed too, but it is not used in the real test. To validate this...

  3. Approaches to open quantum systems: Decoherence, localisation and all that

    International Nuclear Information System (INIS)

    Yu Ting

    1998-01-01

    This thesis is mainly concerned with issues in quantum open systems and the foundations of quantum theory. Chapter I introduces the aim, background and main results which take place in the following chapters. Chapters II and III are used to study and compare the decoherent histories approach, the environment-induced decoherence and the localisation properties of the solutions to the stochastic Schrodinger equation in quantum jump simulation and quantum state diffusion approaches, for a quantum two-level system model. We show, in particular, that there is a close connection between the decoherent histories and the quantum jump simulation, complementing a connection with the quantum state diffusion approach noted earlier by Diosi, Gisin, Halliwell and Percival. In the case of the decoherent histories analysis, the degree of approximate decoherence is discussed in detail. As by-product, by using the von Neumann entropy, we also discuss the predictability and its relation to the upper bounds of degree of decoherence. In Chapter IV, we give an alternative and elementary derivation of the Hu-Paz-Ghang master equation for quantum Brownian motion in a general environment, which involves tracing the evolution equation for the Wigner function. We also discuss the master equation in some special cases. This master equation provides a very useful tool to study the decoherence of a quantum system due to the interaction with its environment. In Chapter V, a derivation of the parameter-based uncertainty relation between position and momentum is given. This uncertainty relation can be regarded as an exact counterpart of the time-energy uncertainty relation. The final chapter is a rather brief summary of the thesis. (author)

  4. Initial Australian experience with daily ultrasound localisation for prostate radiotherapy

    International Nuclear Information System (INIS)

    Kneebone, A.; Fuller, M.W.; Williams, M.J.

    2003-01-01

    Variability in prostate position is a major problem in the delivery of external beam radiotherapy (EBRT). Daily ultrasound localisation prior to radiotherapy has become popular in the United States but to date has not been used clinically in Australia or New Zealand. Daily transabdominal ultrasound images through the prostate were acquired using the BAT ultrasound system. Contour data from the planning system is reconstructed at the same locations/angles as the BAT images. By overlaying the planned contours with the newly acquired images, the isocentre is adjusted to ensure that the prostate will be within the irradiated volume. After commissioning by Medical Physics, an initial pre-clinical trial period was adopted. This involved performing BAT alignments daily but treating to the planned isocentre in 30 patients. Eighty three percent of patients (25/30) had images judged to be of good or excellent quality by the reviewing radiation oncologist. It was noted that for each operator there was a period needed to build confidence/competence in both imaging and interpreting the images for the moves. The median scan time in addition to the normal patient set-up was 3.2 minutes (range=1.5-12.0 mins) with the second 15 patients scanned quicker than the first 15 (2.9 minutes versus 3.8 minutes). A summary of the movements recommended by the BAT system is contained in the table. We feel that daily prostate ultrasound localization offers a significant advance in delivering EBRT for prostate cancer. The incorporation of the system into clinical use, however, was not without difficulty and requires significant time and effort from therapists, physicists and medical staff. Further clinical evaluation of the unit is ongoing

  5. Localised uptake and extraction of calcium45 in dinoflagellate nuclei

    International Nuclear Information System (INIS)

    Sigee, D.C.

    1983-01-01

    The uptake of Ca 45 into cells of the dinoflagellate Glenodinium foliaceum was investigated using insoluble compound light microscope autoradiography. The distribution of silver grains showed marked localisation to the dinocaryotic nucleus, with a random scatter of grains over the surrounding protoplasm (cytoplasm and supernumerary nucleus). Correction of grain counts for lateral sensitisation from the dinocaryotic nucleus indicated an isotope concentration 16 32 times greater in this organelle compared to the rest of the cell. Cells labelled for varying periods of time showed differences in the pattern of Ca 45 uptake throughout the sample populations, but no increase in the mean level of uptake per cell. This would suggest a rapid incorporation of isotope within 1-2 hours, with little subsequent uptake. The presence of high levels of label after processing with both additive (glutaraldehyde, paraformaldehyde) and coagulative (acetic alcohol) fixatives indicated that the retention of Ca 45 in these preparations was not simply a fixation artefact. Although the isotope did not appear to be suitable for (high resolution) electron microscope autoradiography, the intranuclear site of incorporation was demonstrated indirectly using a buffer extraction technique. Prolonged treatment with phosphate buffer resulted in a large scale loss of label from both cytoplasm and dinocaryotic nucleus. The latter appeared to show specific correlation with the loss of (protein) matrix from the chromosomes - as observed under both light and electron microscopy, with no apparent change in either nucleolus or nucleoplasm. This would suggest that incorporated Ca 45 in the nucleus was largely confined to the condensed chromatin, where it was combined with the acidic proteins which make up the bulk of the chromatin matrix. The results obtained in this investigation are related to previous studies involving X-ray microanalysis and uptake of Ni 63 . (Author)

  6. Rac1 is essential for phospholipase C-gamma2 activation in platelets

    DEFF Research Database (Denmark)

    Pleines, Irina; Elvers, Margitta; Strehl, Amrei

    2008-01-01

    isoenzymes are activated downstream of G protein-coupled receptors (GPCRs), whereas PLCgamma2 is activated downstream of immunoreceptor tyrosine-based activation motif (ITAM)-coupled receptors, such as the major platelet collagen receptor glycoprotein (GP) VI or CLEC-2. The mechanisms underlying PLC......Platelet activation at sites of vascular injury is triggered through different signaling pathways leading to activation of phospholipase (PL) Cbeta or PLCgamma2. Active PLCs trigger Ca(2+) mobilization and entry, which is a prerequisite for adhesion, secretion, and thrombus formation. PLCbeta...... regulation are not fully understood. An involvement of small GTPases of the Rho family (Rho, Rac, Cdc42) in PLC activation has been proposed but this has not been investigated in platelets. We here show that murine platelets lacking Rac1 display severely impaired GPVI- or CLEC-2-dependent activation...

  7. Bacillus anthracis TIR Domain-Containing Protein Localises to Cellular Microtubule Structures and Induces Autophagy.

    Science.gov (United States)

    Carlsson, Emil; Thwaite, Joanne E; Jenner, Dominic C; Spear, Abigail M; Flick-Smith, Helen; Atkins, Helen S; Byrne, Bernadette; Ding, Jeak Ling

    2016-01-01

    Toll-like receptors (TLRs) recognise invading pathogens and mediate downstream immune signalling via Toll/IL-1 receptor (TIR) domains. TIR domain proteins (Tdps) have been identified in multiple pathogenic bacteria and have recently been implicated as negative regulators of host innate immune activation. A Tdp has been identified in Bacillus anthracis, the causative agent of anthrax. Here we present the first study of this protein, designated BaTdp. Recombinantly expressed and purified BaTdp TIR domain interacted with several human TIR domains, including that of the key TLR adaptor MyD88, although BaTdp expression in cultured HEK293 cells had no effect on TLR4- or TLR2- mediated immune activation. During expression in mammalian cells, BaTdp localised to microtubular networks and caused an increase in lipidated cytosolic microtubule-associated protein 1A/1B-light chain 3 (LC3), indicative of autophagosome formation. In vivo intra-nasal infection experiments in mice showed that a BaTdp knockout strain colonised host tissue faster with higher bacterial load within 4 days post-infection compared to the wild type B. anthracis. Taken together, these findings indicate that BaTdp does not play an immune suppressive role, but rather, its absence increases virulence. BaTdp present in wild type B. anthracis plausibly interact with the infected host cell, which undergoes autophagy in self-defence.

  8. Sub-cellular localisation studies may spuriously detect the Yes-associated protein, YAP, in nucleoli leading to potentially invalid conclusions of its function.

    Science.gov (United States)

    Finch, Megan L; Passman, Adam M; Strauss, Robyn P; Yeoh, George C; Callus, Bernard A

    2015-01-01

    The Yes-associated protein (YAP) is a potent transcriptional co-activator that functions as a nuclear effector of the Hippo signaling pathway. YAP is oncogenic and its activity is linked to its cellular abundance and nuclear localisation. Activation of the Hippo pathway restricts YAP nuclear entry via its phosphorylation by Lats kinases and consequent cytoplasmic retention bound to 14-3-3 proteins. We examined YAP expression in liver progenitor cells (LPCs) and surprisingly found that transformed LPCs did not show an increase in YAP abundance compared to the non-transformed LPCs from which they were derived. We then sought to ascertain whether nuclear YAP was more abundant in transformed LPCs. We used an antibody that we confirmed was specific for YAP by immunoblotting to determine YAP's sub-cellular localisation by immunofluorescence. This antibody showed diffuse staining for YAP within the cytosol and nuclei, but, noticeably, it showed intense staining of the nucleoli of LPCs. This staining was non-specific, as shRNA treatment of cells abolished YAP expression to undetectable levels by Western blot yet the nucleolar staining remained. Similar spurious YAP nucleolar staining was also seen in mouse embryonic fibroblasts and mouse liver tissue, indicating that this antibody is unsuitable for immunological applications to determine YAP sub-cellular localisation in mouse cells or tissues. Interestingly nucleolar staining was not evident in D645 cells suggesting the antibody may be suitable for use in human cells. Given the large body of published work on YAP in recent years, many of which utilise this antibody, this study raises concerns regarding its use for determining sub-cellular localisation. From a broader perspective, it serves as a timely reminder of the need to perform appropriate controls to ensure the validity of published data.

  9. Plato: A localised orbital based density functional theory code

    Science.gov (United States)

    Kenny, S. D.; Horsfield, A. P.

    2009-12-01

    The Plato package allows both orthogonal and non-orthogonal tight-binding as well as density functional theory (DFT) calculations to be performed within a single framework. The package also provides extensive tools for analysing the results of simulations as well as a number of tools for creating input files. The code is based upon the ideas first discussed in Sankey and Niklewski (1989) [1] with extensions to allow high-quality DFT calculations to be performed. DFT calculations can utilise either the local density approximation or the generalised gradient approximation. Basis sets from minimal basis through to ones containing multiple radial functions per angular momenta and polarisation functions can be used. Illustrations of how the package has been employed are given along with instructions for its utilisation. Program summaryProgram title: Plato Catalogue identifier: AEFC_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEFC_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 219 974 No. of bytes in distributed program, including test data, etc.: 1 821 493 Distribution format: tar.gz Programming language: C/MPI and PERL Computer: Apple Macintosh, PC, Unix machines Operating system: Unix, Linux and Mac OS X Has the code been vectorised or parallelised?: Yes, up to 256 processors tested RAM: Up to 2 Gbytes per processor Classification: 7.3 External routines: LAPACK, BLAS and optionally ScaLAPACK, BLACS, PBLAS, FFTW Nature of problem: Density functional theory study of electronic structure and total energies of molecules, crystals and surfaces. Solution method: Localised orbital based density functional theory. Restrictions: Tight-binding and density functional theory only, no exact exchange. Unusual features: Both atom centred and uniform meshes available

  10. Slower resting alpha frequency is associated with superior localisation of moving targets.

    Science.gov (United States)

    Howard, Christina J; Arnold, Craig P A; Belmonte, Matthew K

    2017-10-01

    We examined the neurophysiological underpinnings of individual differences in the ability to maintain up-to-date representations of the positions of moving objects. In two experiments similar to the multiple object tracking (MOT) task, we asked observers to monitor continuously one or several targets as they moved unpredictably for a semi-random period. After all objects disappeared, observers were immediately prompted to report the perceived final position of one queried target. Precision of these position reports declined with attentional load, and reports tended to best resemble positions occupied by the queried target between 0 and 30ms in the past. Measurement of event-related potentials showed a contralateral delay activity over occipital scalp, maximal in the right hemisphere. The peak power-spectral frequency of observers' eyes-closed resting occipital alpha oscillations reliably predicted performance, such that lower-frequency alpha was associated with superior spatial localisation. Slower resting alpha might be associated with a cognitive style that depends less on memory-related processing and instead emphasises attention to changing stimuli. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  11. Cytotoxicity, DNA binding and localisation of novel bis-naphthalimidopropyl polyamine derivatives.

    Science.gov (United States)

    Pavlov, V; Kong Thoo Lin, P; Rodilla, V

    2001-07-31

    Bis-naphthalimidopropyl spermidine (BNIPSpd), spermine (BNIPSpm) and oxa-spermine (BNIPOSpm) showed high in vitro cytotoxicity against human breast cancer MCF-7 cells with IC(50) values of 1.38, 2.91 and 8.45 microM, respectively. These compounds were found to effectively displace the intercalating agent ethidium bromide bound to the calf thymus DNA using fluorimetric methods (C(50) 0.08-0.12 microM) and their apparent equilibrium binding constants (K(app)) were calculated to be in the range of 10.5-18 x 10(7) M(-1). Furthermore, strong stabilisation of calf thymus DNA duplex in the presence of bis-naphthalimidopropyl polyamine derivatives (BNIPSpd, BNIPSpm and BNIPOSpm) was observed by UV spectrophotometric analysis (T(m)=93.3-97 degrees C compared with 75 degrees C for calf thymus DNA without drug). Because of their inherent fluorescence, these compounds were localised preferentially inside the nucleus as evidenced by their direct observation under the fluorescence microscope. The results obtained suggest that the cytotoxic activity of the bis-naphthalimidopropyl polyamines may be in part, caused by their effects on DNA.

  12. The decision-making role of the patient in localised prostate cancer treatment

    Directory of Open Access Journals (Sweden)

    Luke L Wang

    2017-03-01

    Full Text Available Our objective was to review the current literature on patient participation and decision-making in the treatment selection process for localised prostate cancer, and to evaluate capacity for improvement. Methods: 42 articles from our literature search were deemed eligible and relevant for review. We reviewed studies on all facets of the treatment decision-making process with most number of articles (16 on treatment preferences. Results: The majority of the patients prefer an active or collaborative role in decision-making. Patients are seeking information from a myriad of sources but the recommendation from their treating physician is often the most influential on the final decision. Radical prostatectomy is more likely to be selected in patients who view a cure for cancer as being of the utmost importance and radiation therapy is preferred in patients who are concerned about treatment side effects. Conclusion: Currently no ideal tool exists to assist patients in making informed treatment decisions that also takes into account patients’ values and preferences. We encourage collaborative partnership in a multidisciplinary setting to optimise this process and individualised risk-based decision-making tools may provide a better pathway to assist patients reach decisions.

  13. Cdc25A localisation and shuttling: characterisation of sequences mediating nuclear export and import

    International Nuclear Information System (INIS)

    Kaellstroem, Helena; Lindqvist, Arne; Pospisil, Vitek; Lundgren, Andreas; Karlsson Rosenthal, Christina

    2005-01-01

    The Cdc25 phosphatases play crucial roles in cell cycle progression by removing inhibitory phosphates from tyrosine and threonine residues of cyclin-dependent kinases. Cdc25A is an important regulator of the G1/S transition but functions also in the mitotic phase of the human cell cycle. In this paper, we investigate the sub-cellular localisation of exogenously expressed Cdc25A. We show that YFP-Cdc25A is localised both in the nucleus and the cytoplasm of HeLa cells and untransformed fibroblasts. Cell fusion assays and fluorescence loss in photobleaching (FLIP) assays reveal that the localisation is dynamic and the protein shuttles between the nucleus and the cytoplasm. We demonstrate that nuclear export of Cdc25A is partly mediated by an N-terminal nuclear export sequence (NES), in a manner not sensitive to the Exportin 1-inhibitor leptomycin B. A nuclear localisation signal (NLS) is also characterised, mutation of which leads to cytoplasmic localisation of Cdc25A. Our results imply that the Cdc25A phosphatase may interact with substrates and regulators both in the nucleus and the cytoplasm

  14. A new range-free localisation in wireless sensor networks using support vector machine

    Science.gov (United States)

    Wang, Zengfeng; Zhang, Hao; Lu, Tingting; Sun, Yujuan; Liu, Xing

    2018-02-01

    Location information of sensor nodes is of vital importance for most applications in wireless sensor networks (WSNs). This paper proposes a new range-free localisation algorithm using support vector machine (SVM) and polar coordinate system (PCS), LSVM-PCS. In LSVM-PCS, two sets of classes are first constructed based on sensor nodes' polar coordinates. Using the boundaries of the defined classes, the operation region of WSN field is partitioned into a finite number of polar grids. Each sensor node can be localised into one of the polar grids by executing two localisation algorithms that are developed on the basis of SVM classification. The centre of the resident polar grid is then estimated as the location of the sensor node. In addition, a two-hop mass-spring optimisation (THMSO) is also proposed to further improve the localisation accuracy of LSVM-PCS. In THMSO, both neighbourhood information and non-neighbourhood information are used to refine the sensor node location. The results obtained verify that the proposed algorithm provides a significant improvement over existing localisation methods.

  15. Somatostatin receptor scintigraphy and intraoperative gamma probe detection in the localisation and treatment of pancreatic insulinoma

    International Nuclear Information System (INIS)

    Loh, Nelson K.; Macdonald, William B.; Dunne, Marina L.; Rao, Sudhakar

    2009-01-01

    Full text: Aims: We report a case of insulinoma that was successfully enucleated under radio-guidance after an initial unsuccessful laparotomy. This case highlights the utility of Somatostatin Receptor Scintigraphy (SRS) and gamma probe in the localisation and treatment of neuroendocrine tumours. Methods: The patient presented with recurrent hypoglycaemia. An abdominal CT scan identified a lesion in the uncinate process of the pancreas, however, laparotomy with use of intraoperative ultrasound failed to localise the lesion. SRS with SPECTICT was then requested by the surgical team with a view to radio-guided surgery. Results: SRS demonstrated an octreotide-avid tumour in the posterior uncinate process of the pancreas, and confirmed suitability for radio-guided surgery. At re-exploration, the surgeon was again unable to palpate the lesion or localise it with intraoperative ultrasound, however, the lesion was successfully detected and removed with the use of a gamma probe. A postoperative SRS confirmed complete excision and histopathology was diagnostic of insulinoma. Conclusion: This case highlights the utility of SRS in the intraoperative localisation and surgical excision of neuroendocrine tumours. The lesion was unable to be localised clinically or with intraoperative ultrasound but was successfully detected with scintigraphic techniques. The surgical team acknowledge that the use of a gamma probe enabled enucleation of the insulinoma, which obviated the need for an invasive Whipple's procedure.

  16. The Subcellular Localisation of the Human Papillomavirus (HPV 16 E7 Protein in Cervical Cancer Cells and Its Perturbation by RNA Aptamers

    Directory of Open Access Journals (Sweden)

    Özlem Cesur

    2015-06-01

    Full Text Available Human papillomavirus (HPV is the most common viral infection of the reproductive tract, affecting both men and women. High-risk oncogenic types are responsible for almost 90% of anogenital and oropharyngeal cancers including cervical cancer. Some of the HPV “early” genes, particularly E6 and E7, are known to act as oncogenes that promote tumour growth and malignant transformation. Most notably, HPV-16 E7 interacts with the tumour suppressor protein pRb, promoting its degradation, leading to cell cycle dysregulation in infected cells. We have previously shown that an RNA aptamer (termed A2 selectively binds to HPV16 E7 and is able to induce apoptosis in HPV16-transformed cervical carcinoma cell lines (SiHa through reduction of E7 levels. In this study, we investigated the effects of the A2 aptamer on E7 localisation in order to define its effects on E7 activity. We demonstrate for the first time that E7 localised to the plasma membrane. In addition, we show that A2 enhanced E7 localisation in the ER and that the A2-mediated reduction of E7 was not associated with proteasomal degradation. These data suggest that A2 perturbs normal E7 trafficking through promoting E7 ER retention.

  17. Flows and Stratification of an Enclosure Containing Both Localised and Vertically Distributed Sources of Buoyancy

    Science.gov (United States)

    Partridge, Jamie; Linden, Paul

    2013-11-01

    We examine the flows and stratification established in a naturally ventilated enclosure containing both a localised and vertically distributed source of buoyancy. The enclosure is ventilated through upper and lower openings which connect the space to an external ambient. Small scale laboratory experiments were carried out with water as the working medium and buoyancy being driven directly by temperature differences. A point source plume gave localised heating while the distributed source was driven by a controllable heater mat located in the side wall of the enclosure. The transient temperatures, as well as steady state temperature profiles, were recorded and are reported here. The temperature profiles inside the enclosure were found to be dependent on the effective opening area A*, a combination of the upper and lower openings, and the ratio of buoyancy fluxes from the distributed and localised source Ψ =Bw/Bp . Industrial CASE award with ARUP.

  18. Neuromorphic Audio-Visual Sensor Fusion on a Sound-Localising Robot

    Directory of Open Access Journals (Sweden)

    Vincent Yue-Sek Chan

    2012-02-01

    Full Text Available This paper presents the first robotic system featuring audio-visual sensor fusion with neuromorphic sensors. We combine a pair of silicon cochleae and a silicon retina on a robotic platform to allow the robot to learn sound localisation through self-motion and visual feedback, using an adaptive ITD-based sound localisation algorithm. After training, the robot can localise sound sources (white or pink noise in a reverberant environment with an RMS error of 4 to 5 degrees in azimuth. In the second part of the paper, we investigate the source binding problem. An experiment is conducted to test the effectiveness of matching an audio event with a corresponding visual event based on their onset time. The results show that this technique can be quite effective, despite its simplicity.

  19. Deconfinement, chiral transition and localisation in a QCD-like model

    Energy Technology Data Exchange (ETDEWEB)

    Giordano, Matteo; Katz, Sándor D. [Institute for Theoretical Physics, Eötvös University,Pázmány P. sétány 1/A, H-1117 Budapest (Hungary); MTA-ELTE “Lendület” Lattice Gauge Theory Research Group,Pázmány P. sétány 1/A, H-1117 Budapest (Hungary); Kovács, Tamás G. [Institute for Nuclear Research of the Hungarian Academy of Sciences,Bem tér 18/c, H-4026 Debrecen (Hungary); Pittler, Ferenc [HISKP(Theory), University of Bonn,Nussallee 14-16, D-53115 Bonn (Germany)

    2017-02-10

    We study the problems of deconfinement, chiral symmetry restoration and localisation of the low Dirac eigenmodes in a toy model of QCD, namely unimproved staggered fermions on lattices of temporal extension N{sub T}=4. This model displays a genuine deconfining and chirally-restoring first-order phase transition at some critical value of the gauge coupling. Our results indicate that the onset of localisation of the lowest Dirac eigenmodes takes place at the same critical coupling where the system undergoes the first-order phase transition. This provides further evidence of the close relation between deconfinement, chiral symmetry restoration and localisation of the low modes of the Dirac operator on the lattice.

  20. Towards a Multimodal Methodology for the Analysis of Translated/Localised Games

    Directory of Open Access Journals (Sweden)

    Bárbara Resende Coelho

    2016-12-01

    Full Text Available Multimedia materials require research methodologies that are able to comprehend all of their assets. Videogames are the epitome of multimedia, joining image, sound, video, animation, graphics and text with the interactivity factor. A methodology to conduct research into translation and localisation of videogames should be able to analyse all of its assets and features. This paper sets out to develop a research methodology for games and their translations/localisations that goes beyond the collection and analysis of “screenshots” and includes as many of their assets as possible. Using the fully localised version of the game Watchdogs, this papers shows how tools and technologies allow for transcending the mere analysis of linguistic contents within multimedia materials. Using software ELAN Language Archive to analyse Portuguese-language dubbed and English-language subtitled excerpts from the videogame, it was possible to identify patterns in both linguistic and audio-visual elements, as well as to correlate them.

  1. Interdependency of formation and localisation of the Min complex controls symmetric plastid division.

    Science.gov (United States)

    Maple, Jodi; Møller, Simon G

    2007-10-01

    Plastid division represents a fundamental biological process essential for plant development; however, the molecular basis of symmetric plastid division is unclear. AtMinE1 plays a pivotal role in selection of the plastid division site in concert with AtMinD1. AtMinE1 localises to discrete foci in chloroplasts and interacts with AtMinD1, which shows a similar localisation pattern. Here, we investigate the importance of Min protein complex formation during the chloroplast division process. Dissection of the assembly of the Min protein complex and determination of the interdependency of complex assembly and localisation in planta allow us to present a model of the molecular basis of selection of the division site in plastids. Moreover, functional analysis of AtMinE1 in bacteria demonstrates the level of functional conservation and divergence of the plastidic MinE proteins.

  2. Cdc42-dependent leading edge coordination is essential for interstitial dendritic cell migration

    DEFF Research Database (Denmark)

    Lammermann, Tim; Renkawitz, Jorg; Wu, Xunwei

    2009-01-01

    Mature dendritic cells (DCs) moving from the skin to the lymph node are a prototypic example of rapidly migrating amoeboid leukocytes. Interstitial DC migration is directionally guided by chemokines, but independent of specific adhesive interactions with the tissue as well as pericellular proteol...

  3. Rho-family GTPase Cdc42 controls migration of Langerhans cells in vivo

    DEFF Research Database (Denmark)

    Luckashenak, Nancy; Wähe, Anna; Breit, Katharina

    2013-01-01

    Epidermal Langerhans cells (LCs) of the skin represent the prototype migratory dendritic cell (DC) subtype. In the skin, they take up Ag, migrate to the draining lymph nodes, and contribute to Ag transport and immunity. Different depletion models for LCs have revealed contrasting roles and contri...

  4. A Cdc42/RhoA regulatory circuit downstream of glycoprotein Ib guides transendothelial platelet biogenesis

    DEFF Research Database (Denmark)

    Dütting, Sebastian; Gaits-Iacovoni, Frederique; Stegner, David

    2017-01-01

    Blood platelets are produced by large bone marrow (BM) precursor cells, megakaryocytes (MKs), which extend cytoplasmic protrusions (proplatelets) into BM sinusoids. The molecular cues that control MK polarization towards sinusoids and limit transendothelial crossing to proplatelets remain unknown...

  5. Techniques avancées du traitement d'antennes pour la localisation de sources : application à la localisation de mobile: cas du système UMTS.

    OpenAIRE

    Grosicki , Emmanuele

    2003-01-01

    La thèse a porté sur la localisation de mobile pour les systèmes UMTS-FDD. Il s'agit d'un sujet qui intéresse de plus en plus les opérateurs, notamment dans le cas de système UMTS-FDD où il existe très peu de réseaux réels. Les différentes approches permettant de localiser un émetteur ont ainsi été envisagées, et plus particulièrement, celles basées sur les mesures de puissances, les temps d'arrivée (TOA) en liaison descendante ou encore celles basées sur les angles d'arrivée (AOA) et sur tou...

  6. Divergent RNA Localisation Patterns of Maternal Genes Regulating Embryonic Patterning in the Butterfly Pararge aegeria.

    Directory of Open Access Journals (Sweden)

    Jean-Michel Carter

    Full Text Available The maternal effect genes responsible for patterning the embryo along the antero-posterior (AP axis are broadly conserved in insects. The precise function of these maternal effect genes is the result of the localisation of their mRNA in the oocyte. The main developmental mechanisms involved have been elucidated in Drosophila melanogaster, but recent studies have shown that other insect orders often diverge in RNA localisation patterns. A recent study has shown that in the butterfly Pararge aegeria the distinction between blastodermal embryonic (i.e. germ band and extra-embryonic tissue (i.e. serosa is already specified in the oocyte during oogenesis in the ovariole, long before blastoderm cellularisation. To examine the extent by which a female butterfly specifies and patterns the AP axis within the region fated to be the germ band, and whether she specifies a germ plasm, we performed in situ hybridisation experiments on oocytes in P. aegeria ovarioles and on early embryos. RNA localisation of the following key maternal effect genes were investigated: caudal (cad, orthodenticle (otd, hunchback (hb and four nanos (nos paralogs, as well as TDRD7 a gene containing a key functional domain (OST-HTH/LOTUS shared with oskar. TDRD7 was mainly confined to the follicle cells, whilst hb was exclusively zygotically transcribed. RNA of some of the nos paralogs, otd and cad revealed complex localisation patterns within the cortical region prefiguring the germ band (i.e. germ cortex. Rather interestingly, otd was localised within and outside the anterior of the germ cortex. Transcripts of nos-O formed a distinct granular ring in the middle of the germ cortex possibly prefiguring the region where germline stem cells form. These butterfly RNA localisation patterns are highly divergent with respect to other insects, highlighting the diverse ways in which different insect orders maternally regulate early embryogenesis of their offspring.

  7. Divergent RNA Localisation Patterns of Maternal Genes Regulating Embryonic Patterning in the Butterfly Pararge aegeria

    Science.gov (United States)

    Carter, Jean-Michel; Gibbs, Melanie; Breuker, Casper J.

    2015-01-01

    The maternal effect genes responsible for patterning the embryo along the antero-posterior (AP) axis are broadly conserved in insects. The precise function of these maternal effect genes is the result of the localisation of their mRNA in the oocyte. The main developmental mechanisms involved have been elucidated in Drosophila melanogaster, but recent studies have shown that other insect orders often diverge in RNA localisation patterns. A recent study has shown that in the butterfly Pararge aegeria the distinction between blastodermal embryonic (i.e. germ band) and extra-embryonic tissue (i.e. serosa) is already specified in the oocyte during oogenesis in the ovariole, long before blastoderm cellularisation. To examine the extent by which a female butterfly specifies and patterns the AP axis within the region fated to be the germ band, and whether she specifies a germ plasm, we performed in situ hybridisation experiments on oocytes in P. aegeria ovarioles and on early embryos. RNA localisation of the following key maternal effect genes were investigated: caudal (cad), orthodenticle (otd), hunchback (hb) and four nanos (nos) paralogs, as well as TDRD7 a gene containing a key functional domain (OST-HTH/LOTUS) shared with oskar. TDRD7 was mainly confined to the follicle cells, whilst hb was exclusively zygotically transcribed. RNA of some of the nos paralogs, otd and cad revealed complex localisation patterns within the cortical region prefiguring the germ band (i.e. germ cortex). Rather interestingly, otd was localised within and outside the anterior of the germ cortex. Transcripts of nos-O formed a distinct granular ring in the middle of the germ cortex possibly prefiguring the region where germline stem cells form. These butterfly RNA localisation patterns are highly divergent with respect to other insects, highlighting the diverse ways in which different insect orders maternally regulate early embryogenesis of their offspring. PMID:26633019

  8. Localised sarcoptic mange in dogs: a retrospective study of 10 cases.

    Science.gov (United States)

    Pin, D; Bensignor, E; Carlotti, D-N; Cadiergues, M C

    2006-10-01

    The authors report 10 cases of localised sarcoptic mange in dogs. In each case, lesions were localised to one precise area of the skin. Pruritus was present in nine cases and absent in one. Affected areas were the feet (one case), the face and/or the pinnae (six cases), the abdominal skin (one case), the flank (one case) and the lumbar area (one case). The types of lesions were erythema, papules, lichenification, scales, crusts and alopecia. Parasites were found in all cases except one, in which anti-immunoglobulin G Sarcoptes serology was positive. The acaricidal treatments given were lindane, ivermectin or selamectin and were all successful.

  9. Localisation of lung cancer by a radiolabelled monoclonal antibody against the c-myc oncogene product

    Energy Technology Data Exchange (ETDEWEB)

    Chan, S Y.T.; Evan, G I; Ritson, A; Watson, J; Wraight, P; Sikora, K

    1986-11-01

    A set of mouse monoclonal antibodies against the c-myc oncogene product, a 62,000 dalton nuclear binding protein involved in cell cycle control, has been constructed by immunisation with synthetic peptide fragments. One such antibody, CT14, was radiolabelled with /sup 131/I and administered to 20 patients with different malignant diseases. Good tumour localisation was observed in 12 out of 14 patients with primary bronchial carcinoma but not in patients with pulmonary metastases from primary tumours elsewhere. Successfully localised tumours were all 3 cm or more in diameter. Monoclonal antibodies against oncogene products may provide novel selective tools for the diagnosis and therapy of cancer.

  10. Accuracy of target localisation and alignment in stereotactic radiosurgery at Royal Prince Alfred Hospital

    International Nuclear Information System (INIS)

    Downes, S.

    1996-01-01

    Full text: Over the last 30 years, stereotactic radiosurgery has become an effective clinical tool in the treatment of intra-cranial lesions. The use of high doses to a specific target volume in a single fraction and the proximity of critical organs requires very accurate geometric localisation of the various cranial structures (using CT, MRI and angiography imaging) and accurate alignment of the target volume prior to treatment. The purpose of this paper was to determine the accuracy of localising cranial structures using computed tomography and angiographic imaging modalities and to determine the accuracy of aligning the treatment isocentre to the specified coordinates. The sum of these two errors will give the total deviation of the treated target from the actual target. Measurements were made using an anthropomorphic (ART) phantom of an adult male and a cerrobend target. The ART phantom was immobilised using the Brown-Roberts-Wells (BRW) ring. The cerrobend target was inserted into the skull at 10 different positions. Each of these 10 positions were scanned using CT and angiographic imaging and localised using the stereotactic planning software. For each test position, the ART phantom was placed on the treatment couch and aligned to the treatment coordinates determined using localisation (CT and angiography). A-P and lateral port films were then made of the target. The distance between the centre of the cerrobend target (intended target) and the centre of radiation (actual target) was the total error in localisation and alignment of the target. For computed tomography, the measurements showed the average error in localisation and alignment of the target was ±0.7mm. In terms of coordinate axis, the average error was: A-P axis = ±0.5mm, Lateral(left-right) Axis = ±0.3mm, Vertical(inferior superior) Axis ±0.4mm. From these measurements it was shown that using the stereotactic radiosurgery planning system and hardware, cranial lesions could be localised and

  11. Real time fMRI: a tool for the routine presurgical localisation of the motor cortex

    Energy Technology Data Exchange (ETDEWEB)

    Moeller, M.; Freund, M.; Schwindt, W.; Gaus, C.; Heindel, W. [University of Muenster, Department of Clinical Radiology, Munster (Germany); Greiner, C. [University of Muenster, Department of Neurosurgery, Munster (Germany)

    2005-02-01

    In patients with brain lesions adjacent to the central area, exact preoperative knowledge of the spatial relation of the tumour to the motor cortex is of major importance. Many studies have shown that functional magnetic resonance imaging (fMRI) is a reliable tool to identify the motor cortex. However, fMRI data acquisition and data processing are time-consuming procedures, and this prevents general routine clinical application. We report a new application of real time fMRI that allows immediate access to fMRI results by automatic on-line data processing. Prior to surgery we examined ten patients with a brain tumour adjacent to the central area. Three measurements were performed at a 1.5-T Magnetom Vision Scanner (Siemens, Forchheim, Germany) on seven patients and at a 1.5-T Intera Scanner (Philips, Best, The Netherlands) on three patients using a sequential finger-tapping paradigm for motor cortex activation versus at rest condition. Blood oxygen level-dependant (BOLD) images were acquired using a multislice EPI sequence (16 slices, TE 60, TR 6000, FOV 210 x 210, matrix 64 x 64). The central sulcus of the left hemisphere could be clearly identified by a maximum of cortical activity after finger tapping of the right hand in all investigated patients. In eight of ten patients the right central sulcus was localised by a signal maximum, whereas in two patients the central sulcus could not be identified due to a hemiparesis in one and strong motion artefacts in the second patient. Finger tapping with one side versus rest condition seems to result in more motion artefacts, while finger tapping of the right versus the left hand yielded the strongest signal in the central area. Real time fMRI is a quick and reliable method to identify the central sulcus and has the potential to become a clinical tool to assess patients non-invasively before neurosurgical treatment. (orig.)

  12. Functional analysis and localisation of a delta-class glutathione S-transferase from Sarcoptes scabiei.

    Science.gov (United States)

    Pettersson, Eva U; Ljunggren, Erland L; Morrison, David A; Mattsson, Jens G

    2005-01-01

    The mite Sarcoptes scabiei causes sarcoptic mange, or scabies, a disease that affects both animals and humans worldwide. Our interest in S. scabiei led us to further characterise a glutathione S-transferase. This multifunctional enzyme is a target for vaccine and drug development in several parasitic diseases. The S. scabiei glutathione S-transferase open reading frame reported here is 684 nucleotides long and yields a protein with a predicted molecular mass of 26 kDa. Through phylogenetic analysis the enzyme was classified as a delta-class glutathione S-transferase, and our paper is the first to report that delta-class glutathione S-transferases occur in organisms other than insects. The recombinant S. scabiei glutathione S-transferase was expressed in Escherichia coli via three different constructs and purified for biochemical analysis. The S. scabiei glutathione S-transferase was active towards the substrate 1-chloro-2,4-dinitrobenzene, though the positioning of fusion partners influenced the kinetic activity of the enzyme. Polyclonal antibodies raised against S. scabiei glutathione S-transferase specifically localised the enzyme to the integument of the epidermis and cavities surrounding internal organs in adult parasites. However, some minor staining of parasite intestines was observed. No staining was seen in host tissues, nor could we detect any antibody response against S. scabiei glutathione S-transferase in sera from naturally S. scabiei infected dogs or pigs. Additionally, the polyclonal sera raised against recombinant S. scabiei glutathione S-transferase readily detected a protein from mites, corresponding to the predicted size of native glutathione S-transferase.

  13. The CREC family, a novel family of multiple EF-hand, low-affinity Ca(2+)-binding proteins localised to the secretory pathway of mammalian cells

    DEFF Research Database (Denmark)

    Honoré, B; Vorum, H

    2000-01-01

    The CREC family consists of a number of recently discovered multiple (up to seven) EF-hand proteins that localise to the secretory pathway of mammalian cells. At present, the family includes reticulocalbin, ERC-55/TCBP-49/E6BP, Cab45, calumenin and crocalbin/CBP-50. Similar proteins are found......(2+)-regulated activities. Recent evidence has been obtained that some CREC family members are involved in pathological activities such as malignant cell transformation, mediation of the toxic effects of snake venom toxins and putative participation in amyloid formation. Udgivelsesdato: 2000-Jan-21...

  14. Modernization of the accident localisation system and relevant dose exposure on unit four of KNPP

    International Nuclear Information System (INIS)

    Valtchev, G.; Neshkova, M.; Nikilov, A.

    2005-01-01

    In 2001 a modernization of the accident localisation system (ALS) on Unit 4 was accomplished. The outage duration was longer then usually and special dose budget was elaborated. All ALS work was performed by external organisation. An ALARA implementation was recognised priority. The really accumulated collective doses were analysed and conclusions drawn. A short film on CD was prepared. (authors)

  15. Quantitation and localisation of (in vitro) transglutaminase-catalysed glutamine hydroxylation using mass spectrometry

    NARCIS (Netherlands)

    Piersma, S.R.; Pijpekamp, A. van de; Wijngaards, G.; Gruppen, H.; Boumans, H.

    2002-01-01

    A mass spectrometric approach was chosen to quantify and localise in vitro enzymatically modified glutamine (Gln) residues in a glutamine-rich protein. This protein (named dB1), a cloned domain of the high molecular weight wheat glutenin subunit Dx5, was modified by microbial transglutaminase

  16. An efficient approach to node localisation and tracking in wireless sensor networks

    CSIR Research Space (South Africa)

    Mwila, MK

    2014-12-01

    Full Text Available and efficient localisation method that makes use of an improved RSSI distance estimation model by including the antenna radiation pattern as well as nodes orientations is presented. Mathematical models for distance estimation, cost function and gradient of cost...

  17. Localised and Learnt Applications of Machine Learning for Robotic Incremental Sheet Forming

    DEFF Research Database (Denmark)

    Nicholas, Paul; Zwierzycki, Mateusz; Ramsgaard Thomsen, Mette

    2017-01-01

    Sheet Forming (ISF) and exemplified in the fabrication of a bridge structure. The methods we describe compensate for springback and improve forming tolerance by using localised in-process distance sensing to adapt tool-paths, and by using pre-process supervised machine learning to predict stringback...

  18. Immunohistochemical localisation and developmental aspects of epidermal growth factor in the rat

    DEFF Research Database (Denmark)

    Raaberg, L; Nexø, E; Damsgaard Mikkelsen, J

    1988-01-01

    The tissue localisation and time of first appearance of Epidermal Growth Factor (EGF) in the developing rat were investigated by means of immunohistochemistry, radioimmunoassay and radioreceptor assay. In this study we were able to show, that EGF appears prenatally in the lung and the kidney from...

  19. Mozart's African jacket: Die Zauberflöte and its localisation in The ...

    African Journals Online (AJOL)

    , the change in time, space, context and symbolism in a localised or indigenised South African version of Mozart's Die Zauberflöte, K. 620. It addresses the lacunae between desiderata expressed in the White Paper on Arts, Culture and ...

  20. Exploiting deep neural networks and head movements for binaural localisation of multiple speakers in reverberant conditions

    DEFF Research Database (Denmark)

    Ma, Ning; Brown, Guy J.; May, Tobias

    2015-01-01

    This paper presents a novel machine-hearing system that exploits deep neural networks (DNNs) and head movements for binaural localisation of multiple speakers in reverberant conditions. DNNs are used to map binaural features, consisting of the complete crosscorrelation function (CCF) and interaural...

  1. Globalisation and Localisation in Music Education in Hong Kong and Taiwan

    Science.gov (United States)

    Ho, Wai-Chung

    2013-01-01

    The purpose of the study is to analyse and discuss the influences of globalisation and localisation on music education in Hong Kong and Taiwan. It argues that the reform of music education concerns changes to the contents of the curriculum that envisage the cultural and political developments that arise from processes of globalisation and…

  2. Tumour Suppressor Adenomatous Polyposis Coli (APC) localisation is regulated by both Kinesin-1 and Kinesin-2

    NARCIS (Netherlands)

    Ruane, Peter T; Gumy, Laura F; Bola, Becky; Anderson, Beverley; Wozniak, Marcin J; Hoogenraad, Casper C; Allan, Victoria J

    2016-01-01

    Microtubules and their associated proteins (MAPs) underpin the polarity of specialised cells. Adenomatous polyposis coli (APC) is one such MAP with a multifunctional agenda that requires precise intracellular localisations. Although APC has been found to associate with kinesin-2 subfamily members,

  3. Localised human impacts on the Harataonga coastal landscape, Great Barrier Island, northern New Zealand

    International Nuclear Information System (INIS)

    Horrocks, M.; Nichol, S.; Cockrem, J.; Shane, P.

    2008-01-01

    Here we present results of analyses of sediment profiles and cores, and coprolites, from Harataonga Bay, Great Barrier Island. Using a range of analyses (sedimentological, plant microfossils, parasitological, microbial, and steroids and myoglobin) we concentrate on human impact and reconstruction of the geomorphology and vegetation of the near-shore environments. Two different sub--environments are represented: dunes and alluvial plain. Dune instability coincides with a major increase in disturbance-related plants (especially ground ferns) as a result of forest clearance. The present form of much of the Harataonga dunes and the swamp at the eastern end of the bay is directly a result of human impact, no earlier than 737 ± 178 14 C yr BP. In the record from the alluvial plain of the main Harataonga watercourse, at the western end of the bay, it is difficult to clearly resolve sedimentary inputs that directly relate to human presence in this former tidal inlet that was open to storm surge and stream floods. The only exception is the slopewash materials forming the terrace surface, sediments of which bear pollen consistent with vegetation disturbance. The landforms are natural but the rate at which the tidal inlet was infilled to form a terrace was accelerated by human activity. The nature and timing of the localised human impacts at Harataonga are consistent with those observed elsewhere on Great Barrier Island and mainland New Zealand. Some of our techniques (e.g. bacteria, steroids) are newly applied to coprolites in New Zealand but none provided any useful information because of poor preservation. (author). 34 refs., 13 figs., 3 tabs

  4. Diagnosis and localisation of insulinoma: the value of modern magnetic resonance imaging in conjunction with calcium stimulation catheterisation.

    Science.gov (United States)

    Druce, Maralyn R; Muthuppalaniappan, Vasantha M; O'Leary, Benjamin; Chew, Shern L; Drake, William M; Monson, John P; Akker, Scott A; Besser, Michael; Sahdev, Anju; Rockall, Andrea; Vyas, Soumil; Bhattacharya, Satya; Matson, Matthew; Berney, Daniel; Reznek, R H; Grossman, Ashley B

    2010-05-01

    Preoperative localisation of insulinoma improves cure rate and reduces complications, but may be challenging. To review diagnostic features and localisation accuracy for insulinomas. Cross-sectional, retrospective analysis. A single tertiary referral centre. Patients with insulinoma in the years 1990-2009, including sporadic tumours and those in patients with multiple endocrine neoplasia syndromes. Patients were identified from a database, and case notes and investigation results were reviewed. Tumour localisation by computed tomography (CT), magnetic resonance imaging (MRI), octreotide scanning, endoscopic ultrasound (EUS) and calcium stimulation was evaluated. Insulinoma localisation was compared to histologically confirmed location following surgical excision. Thirty-seven instances of biochemically and/or histologically proven insulinoma were identified in 36 patients, of which seven were managed medically. Of the 30 treated surgically, 25 had CT (83.3%) and 28 had MRI (90.3%), with successful localisation in 16 (64%) by CT and 21 (75%) by MRI respectively. Considered together, such imaging correctly localised 80% of lesions. Radiolabelled octreotide scanning was positive in 10 out of 20 cases (50%); EUS correctly identified 17 lesions in 26 patients (65.4%). Twenty-seven patients had calcium stimulation testing, of which 6 (22%) did not localise, 17 (63%) were correctly localised, and 4 (15%) gave discordant or confusing results. Preoperative localisation of insulinomas remains challenging. A pragmatic combination of CT and especially MRI predicts tumour localisation with high accuracy. Radionuclide imaging and EUS were less helpful but may be valuable in selected cases. Calcium stimulation currently remains useful in providing an additional functional perspective.

  5. Localisation of the Putative Magnetoreceptive Protein Cryptochrome 1b in the Retinae of Migratory Birds and Homing Pigeons.

    Directory of Open Access Journals (Sweden)

    Petra Bolte

    Full Text Available Cryptochromes are ubiquitously expressed in various animal tissues including the retina. Some cryptochromes are involved in regulating circadian activity. Cryptochrome proteins have also been suggested to mediate the primary mechanism in light-dependent magnetic compass orientation in birds. Cryptochrome 1b (Cry1b exhibits a unique carboxy terminus exclusively found in birds so far, which might be indicative for a specialised function. Cryptochrome 1a (Cry1a is so far the only cryptochrome protein that has been localised to specific cell types within the retina of migratory birds. Here we show that Cry1b, an alternative splice variant of Cry1a, is also expressed in the retina of migratory birds, but it is primarily located in other cell types than Cry1a. This could suggest different functions for the two splice products. Using diagnostic bird-specific antibodies (that allow for a precise discrimination between both proteins, we show that Cry1b protein is found in the retinae of migratory European robins (Erithacus rubecula, migratory Northern Wheatears (Oenanthe oenanthe and pigeons (Columba livia. In all three species, retinal Cry1b is localised in cell types which have been discussed as potentially well suited locations for magnetoreception: Cry1b is observed in the cytosol of ganglion cells, displaced ganglion cells, and in photoreceptor inner segments. The cytosolic rather than nucleic location of Cry1b in the retina reported here speaks against a circadian clock regulatory function of Cry1b and it allows for the possible involvement of Cry1b in a radical-pair-based magnetoreception mechanism.

  6. Visualization of the Activity of Rac1 Small GTPase in a Cell

    International Nuclear Information System (INIS)

    Higashi, Morihiro; Yu, Jianyong; Tsuchiya, Hiroshi; Saito, Teruyoshi; Oyama, Toshinao; Kawana, Hidetada; Kitagawa, Motoo; Tamaru, Jun-ichi; Harigaya, Kenichi

    2010-01-01

    Rho family G proteins including Rac regulate a variety of cellular functions, such as morphology, motility, and gene expression. Here we developed a fluorescence resonance energy transfer-based analysis in which we could monitor the activity of Rac1. To detect fluorescence resonance energy transfer, yellow fluorescent protein fused Rac1 and cyan fluorescent protein fused Cdc42-Rac1-interaction-binding domain of Pak1 protein were used as intermolecular probes of FRET. The fluorophores were separated with linear unmixing method. The fluorescence resonance energy transfer efficiency was measured by acceptor photobleaching assisted assay. With these methods, the Rac1 activity was visualized in a cell. The present findings indicate that this approach is sensitive enough to achieve results similar to those from ratiometric fluorescence resonance energy transfer analysis

  7. Nanofibrillar scaffolds induce preferential activation of Rho GTPases in cerebral cortical astrocytes

    Science.gov (United States)

    Tiryaki, Volkan Mujdat; Ayres, Virginia M; Khan, Adeel A; Ahmed, Ijaz; Shreiber, David I; Meiners, Sally

    2012-01-01

    Cerebral cortical astrocyte responses to polyamide nanofibrillar scaffolds versus poly-L-lysine (PLL)-functionalized planar glass, unfunctionalized planar Aclar coverslips, and PLL-functionalized planar Aclar surfaces were investigated by atomic force microscopy and immunocytochemistry. The physical properties of the cell culture environments were evaluated using contact angle and surface roughness measurements and compared. Astrocyte morphological responses, including filopodia, lamellipodia, and stress fiber formation, and stellation were imaged using atomic force microscopy and phalloidin staining for F-actin. Activation of the corresponding Rho GTPase regulators was investigated using immunolabeling with Cdc42, Rac1, and RhoA. Astrocytes cultured on the nanofibrillar scaffolds showed a unique response that included stellation, cell–cell interactions by stellate processes, and evidence of depression of RhoA. The results support the hypothesis that the extracellular environment can trigger preferential activation of members of the Rho GTPase family, with demonstrable morphological consequences for cerebral cortical astrocytes. PMID:22915841

  8. The nature of carrier localisation in polar and nonpolar InGaN/GaN quantum wells

    Energy Technology Data Exchange (ETDEWEB)

    Dawson, P., E-mail: philip.dawson@manchester.ac.uk [School of Physics and Astronomy, Photon Science Institute, University of Manchester, Manchester M13 9PL (United Kingdom); Schulz, S. [Photonics Theory Group, Tyndall National Institute, Dyke Parade, Cork (Ireland); Oliver, R. A.; Kappers, M. J.; Humphreys, C. J. [Department of Material Science and Metallurgy, 27 Charles Babbage Road, University of Cambridge, Cambridge CB3 0FS (United Kingdom)

    2016-05-14

    In this paper, we compare and contrast the experimental data and the theoretical predictions of the low temperature optical properties of polar and nonpolar InGaN/GaN quantum well structures. In both types of structure, the optical properties at low temperatures are governed by the effects of carrier localisation. In polar structures, the effect of the in-built electric field leads to electrons being mainly localised at well width fluctuations, whereas holes are localised at regions within the quantum wells, where the random In distribution leads to local minima in potential energy. This leads to a system of independently localised electrons and holes. In nonpolar quantum wells, the nature of the hole localisation is essentially the same as the polar case but the electrons are now coulombically bound to the holes forming localised excitons. These localisation mechanisms are compatible with the large photoluminescence linewidths of the polar and nonpolar quantum wells as well as the different time scales and form of the radiative recombination decay curves.

  9. Human perception of indoor environment generated by chilled ceiling combined with mixing ventilation or localised chilled beam under cooling mode

    DEFF Research Database (Denmark)

    Bolashikov, Zhecho Dimitrov; Nygaard, Linette; Uth, Simon C.

    2014-01-01

    Experiments with 24 subjects were performed to study and compare the human perception of the indoor environment under summer conditions generated by a chilled ceiling combined with overhead mixing ventilation and localised chilled beam. The experiments were performed in an experimental chamber (4....../s and 16 0C. The localised chilled beam was installed over the workstation placed by the simulated window. During the experiment the subjects were delegated control over the primary flow rate supplied by the localised chilled beam. The whole exposure lasted 2 hours with 30 min of acclimatisation before...

  10. Quantification of local morphodynamics and local GTPase activity by edge evolution tracking.

    Directory of Open Access Journals (Sweden)

    Yuki Tsukada

    2008-11-01

    Full Text Available Advances in time-lapse fluorescence microscopy have enabled us to directly observe dynamic cellular phenomena. Although the techniques themselves have promoted the understanding of dynamic cellular functions, the vast number of images acquired has generated a need for automated processing tools to extract statistical information. A problem underlying the analysis of time-lapse cell images is the lack of rigorous methods to extract morphodynamic properties. Here, we propose an algorithm called edge evolution tracking (EET to quantify the relationship between local morphological changes and local fluorescence intensities around a cell edge using time-lapse microscopy images. This algorithm enables us to trace the local edge extension and contraction by defining subdivided edges and their corresponding positions in successive frames. Thus, this algorithm enables the investigation of cross-correlations between local morphological changes and local intensity of fluorescent signals by considering the time shifts. By applying EET to fluorescence resonance energy transfer images of the Rho-family GTPases Rac1, Cdc42, and RhoA, we examined the cross-correlation between the local area difference and GTPase activity. The calculated correlations changed with time-shifts as expected, but surprisingly, the peak of the correlation coefficients appeared with a 6-8 min time shift of morphological changes and preceded the Rac1 or Cdc42 activities. Our method enables the quantification of the dynamics of local morphological change and local protein activity and statistical investigation of the relationship between them by considering time shifts in the relationship. Thus, this algorithm extends the value of time-lapse imaging data to better understand dynamics of cellular function.

  11. Une localisation exceptionnelle de la tuberculose vertébrale Mal de Pott sous-occipital

    Science.gov (United States)

    Yahyaoui, Sana; Majdoub, Senda; Zaghouani, Houneida; Fradj, Hosni Ben; Bakir, Dejla; Bouajina, Elyes; Kraiem, Chakib

    2013-01-01

    Le mal de Pott est la forme la plus commune de la tuberculose osseuse touchant essentiellement le rachis dorso-lombaire. La localisation sous-occipitale reste exceptionnelle. Le diagnostic de cette entité est le plus souvent tardif ce qui expose à des complications graves. Les radiographies standard ne sont parlantes qu’à un stade tardif de la maladie, d'où l'intérêt de l'imagerie moderne notamment la tomodensitométrie (TDM) et l'imagerie par résonance magnétique (IRM) qui permettent un diagnostic précoce. Nous rapportons un nouveau cas de tuberculose sous-occipitale. Le diagnostic était posé sur l'imagerie en coupe et confirmé histologiquement à la biopsie transorale. Sont rappelés les aspects en imagerie de cette localisation particulière du mal de Pott. PMID:23819005

  12. Flow in a circular expansion pipe flow: effect of a vortex perturbation on localised turbulence

    Energy Technology Data Exchange (ETDEWEB)

    Selvam, Kamal; Peixinho, Jorge [Laboratoire Ondes Milieux Complexes, CNRS and Université du Havre, F-76600 Le Havre (France); Willis, Ashley P, E-mail: jorge.peixinho@univ-lehavre.fr [School of Mathematics and Statistics, University of Sheffield, Sheffield S3 7RH (United Kingdom)

    2016-12-15

    We report the results of three-dimensional direct numerical simulations for incompressible viscous fluid in a circular pipe flow with a sudden expansion. At the inlet, a parabolic velocity profile is applied together with a finite amplitude perturbation in the form of a vortex with its axis parallel to the axis of the pipe. At sufficiently high Reynolds numbers the recirculation region breaks into a turbulent patch that changes position axially, depending on the strength of the perturbation. This vortex perturbation is believed to produce a less abrupt transition than in previous studies, which applied a tilt perturbation, as the localised turbulence is observed via the formation of a wavy structure at a low order azimuthal mode, which resembles an optimally amplified perturbation. For large vortex amplitude, the localised turbulence remains at a constant axial position. It is further investigated using proper orthogonal decomposition, which indicates that the centre region close to the expansion is highly energetic. (paper)

  13. Association between PSA kinetics and cancer-specific mortality in patients with localised prostate cancer

    DEFF Research Database (Denmark)

    Thomsen, Frederik Birkebæk; Brasso, Klaus; Berg, Kasper Drimer

    2016-01-01

    BACKGROUND: The prognostic value of prostate-specific antigen (PSA) kinetics in untreated prostate cancer (PCa) patients is debatable. We investigated the association between PSA doubling time (PSAdt), PSA velocity (PSAvel) and PSAvel risk count (PSAvRC) and PCa mortality in a cohort of patients...... with localised PCa managed on watchful waiting. PATIENTS AND METHODS: Patients with clinically localised PCa managed observationally, who were randomised to and remained on placebo for minimum 18 months in the SPCG-6 study, were included. All patients survived at least 2 years and had a minimum of three PSA...... determinations available. The prognostic value of PSA kinetics was analysed and patients were stratified according to their PSA at consent: ≤10, 10.1-25, and >25 ng/ml. Cumulative incidences of PCa-specific mortality were estimated with the Aalen-Johansen method. RESULTS: Two hundred and sixty-three patients...

  14. Aesthetic Proximity: the Role of Stylistic Programme Elements in Format Localisation

    Directory of Open Access Journals (Sweden)

    Jolien van Keulen

    2016-08-01

    Full Text Available Implications of the transnationalisation of television are often studied by focusing on the localisation of the content of formatted programmes. Although television is essentially an audio-visual medium, little attention has been paid to the aesthetic aspects of television texts in relation to transnationalisation and formatting. Transnationalisation of production practices, such as through formatting, implies a transnational aesthetic. At the same time, aspects of style are specific to place, culture or audience. In this article, the localisation of stylistic programme elements is explored using a comparison of two reality format adaptations. It is argued that style plays an important role in the expression of the local in a transnational industry.

  15. Paxillin localisation in osteocytes-Is it determined by the direction of loading?

    International Nuclear Information System (INIS)

    Vatsa, A.; Semeins, C.M.; Smit, T.H.; Klein-Nulend, J.

    2008-01-01

    External mechanical loading of cells aligns cytoskeletal stress fibres in the direction of principle strains and localises paxillin to the mechanosensing region. If the osteocyte cell body can indeed directly sense matrix strains, then cytoskeletal alignment and distribution of paxillin in osteocytes in situ will bear alignment to the different mechanical loading patterns in fibulae and calvariae. We used confocal microscopy to visualise the immunofluorescence-labelled actin cytoskeleton in viable osteocytes and paxillin distribution in fixated osteocytes in situ. In fibular osteocyte cell bodies, actin cytoskeleton and nuclei were elongated and aligned parallel to the principal (longitudinal) mechanical loading direction. Paxillin was localised to the 'poles' of elongated osteocyte cell bodies. In calvarial osteocyte cell bodies, actin cytoskeleton and nuclei were relatively more round. Paxillin was distributed evenly in the osteocyte cell bodies. Thus in osteocyte cell bodies in situ, the external mechanical loading pattern likely determines the orientation of the actin cytoskeleton, and focal adhesions mediate direct mechanosensation of matrix strains.

  16. Photon counting imaging and centroiding with an electron-bombarded CCD using single molecule localisation software

    International Nuclear Information System (INIS)

    Hirvonen, Liisa M.; Barber, Matthew J.; Suhling, Klaus

    2016-01-01

    Photon event centroiding in photon counting imaging and single-molecule localisation in super-resolution fluorescence microscopy share many traits. Although photon event centroiding has traditionally been performed with simple single-iteration algorithms, we recently reported that iterative fitting algorithms originally developed for single-molecule localisation fluorescence microscopy work very well when applied to centroiding photon events imaged with an MCP-intensified CMOS camera. Here, we have applied these algorithms for centroiding of photon events from an electron-bombarded CCD (EBCCD). We find that centroiding algorithms based on iterative fitting of the photon events yield excellent results and allow fitting of overlapping photon events, a feature not reported before and an important aspect to facilitate an increased count rate and shorter acquisition times.

  17. Controlled light localisation and nonlinear-optical interactions of short laser pulses in holey fibres

    International Nuclear Information System (INIS)

    Fedotov, Andrei B; Zheltikov, Aleksei M; Golovan', Leonid A; Kashkarov, Pavel K; Tarasevitch, A P; Podshivalov, Alexey A; Alfimov, Mikhail V; Ivanov, Anatoliy A; Beloglazov, V I; Haus, J W; Linde, D von der

    2001-01-01

    The influence of the structure of holey-fibre cladding on the effective waveguide mode area and the spectral broadening of femtosecond pulses of titanium-sapphire and forsterite lasers is experimentally studied. These experiments demonstrate that the increase in the air-filling fraction of the holey-fibre cladding may substantially enhance the spectral broadening of laser pulses due to the increase in the degree of light localisation in the fibre core. (femtosecond technologies)

  18. Ureteric angioplasty balloon placement to increase localised dosage of BCG for renal pelvis TCC.

    LENUS (Irish Health Repository)

    Forde, J C

    2012-03-01

    Endoscopic percutaneous resection of a renal pelvis transitional cell carcinoma (TCC) is a viable treatment option in those who would be rendered dialysis dependent following a nephroureterectomy. We report endoscopic percutaneous resection of an upper tract TCC recurrence in a single functioning kidney followed by antegrade renal pelvis BCG instillation with novel placement of inflated angioplasty balloon in the ureter to help localise its effect.

  19. Multisensory stimuli improve relative localisation judgments compared to unisensory auditory or visual stimuli

    OpenAIRE

    Bizley, Jennifer; Wood, Katherine; Freeman, Laura

    2018-01-01

    Observers performed a relative localisation task in which they reported whether the second of two sequentially presented signals occurred to the left or right of the first. Stimuli were detectability-matched auditory, visual, or auditory-visual signals and the goal was to compare changes in performance with eccentricity across modalities. Visual performance was superior to auditory at the midline, but inferior in the periphery, while auditory-visual performance exceeded both at all locations....

  20. Réseau africain consacré à la localisation | CRDI - Centre de ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Ce projet s'attaquera à la question de la localisation et des langues locales dans le domaine des technologies de l'information et de la communication (TIC), au moyen de neuf sous-projets dont voici une brève description. Création de paramètres de lieu - l'équipe créera des paramètres de lieu africains pour 100 grandes ...

  1. Novel maximum likelihood approach for passive detection and localisation of multiple emitters

    Science.gov (United States)

    Hernandez, Marcel

    2017-12-01

    In this paper, a novel target acquisition and localisation algorithm (TALA) is introduced that offers a capability for detecting and localising multiple targets using the intermittent "signals-of-opportunity" (e.g. acoustic impulses or radio frequency transmissions) they generate. The TALA is a batch estimator that addresses the complex multi-sensor/multi-target data association problem in order to estimate the locations of an unknown number of targets. The TALA is unique in that it does not require measurements to be of a specific type, and can be implemented for systems composed of either homogeneous or heterogeneous sensors. The performance of the TALA is demonstrated in simulated scenarios with a network of 20 sensors and up to 10 targets. The sensors generate angle-of-arrival (AOA), time-of-arrival (TOA), or hybrid AOA/TOA measurements. It is shown that the TALA is able to successfully detect 83-99% of the targets, with a negligible number of false targets declared. Furthermore, the localisation errors of the TALA are typically within 10% of the errors generated by a "genie" algorithm that is given the correct measurement-to-target associations. The TALA also performs well in comparison with an optimistic Cramér-Rao lower bound, with typical differences in performance of 10-20%, and differences in performance of 40-50% in the most difficult scenarios considered. The computational expense of the TALA is also controllable, which allows the TALA to maintain computational feasibility even in the most challenging scenarios considered. This allows the approach to be implemented in time-critical scenarios, such as in the localisation of artillery firing events. It is concluded that the TALA provides a powerful situational awareness aid for passive surveillance operations.

  2. Localised Agri-food Systems in Italy: strategies for competitiveness and role of institutional factors

    OpenAIRE

    Mantino, Francesco

    2014-01-01

    This paper focuses on the notion of localised agricultural and agro-food system as unit of analysis (LAFS). LAFSs appear to be as quite resilient and dynamic systems. As we will see, the analysis of exports in the last years can provide enough evidence of their strong resilience and capability to respond to economic crisis. This dynamics does not seem understandable by only using either classical variables (size of farm holdings, intensity of capital investment, human capital, rate of technol...

  3. State and localisation of the nuclear wastes in France. Index established by the ANDRA observatory

    International Nuclear Information System (INIS)

    1999-01-01

    This index is the seventh edition of the the national index on nuclear wastes state and localisation. Its purpose is to index the sites where people could find radioactive wastes in France (great industry as EDF or Cogema but also little producers, national defense sites and research laboratories) and the sealed sources distributors. Law texts concerning the radioactive wastes and general information on nuclear elements or radioactivity are also provided. (A.L.B.)

  4. Group-based Motion Detection for Energy-Efficient Localisation

    Directory of Open Access Journals (Sweden)

    Alban Cotillon

    2012-10-01

    Full Text Available Long-term outdoor localization remains challenging due to the high energy profiles of GPS modules. Duty cycling the GPS module combined with inertial sensors can improve energy consumption. However, inertial sensors that are kept active all the time can also drain mobile node batteries. This paper proposes duty cycling strategies for inertial sensors to maintain a target position accuracy and node lifetime. We present a method for duty cycling motion sensors according to features of movement events, and evaluate its energy and accuracy profile for an empirical data trace of cattle movement. We further introduce the concept of group-based duty cycling, where nodes that cluster together can share the burden of motion detection to reduce their duty cycles. Our evaluation shows that both variants of motion sensor duty cycling yield up to 78% improvement in overall node power consumption, and that the group-based method yields an additional 20% power reduction during periods of low mobility.

  5. LOCALISATION OF THE E-EDUCATOR MODULE The Malaysian experience

    Directory of Open Access Journals (Sweden)

    Siew Ming THANG

    2009-04-01

    Full Text Available The University of Nottingham, UK and Beijing Foreign Studies University, China have developed a module for training tutors of online learners - one that could be adapted for use in a variety of contexts. The module was piloted at the School of Distance Education, Universiti Sains Malaysia, Penang with eight staff members (six tutors and two local mentors. They undertook to work through the different units of the eEducator module and complete all the eEducator tasks required which include online forums and other online activities. They were also required to complete reflective Blog entries at regular intervals. This paper will share the results of the first three focus group interviews and the Blogs. The findings revealed that the eEducator module curriculum was perceived as highly relevant to the tutors and impacted on their personal and professional development establishing a community of practice for the tutors involved.

  6. Counterintuitive electron localisation from density-functional theory with polarisable solvent models

    Energy Technology Data Exchange (ETDEWEB)

    Dale, Stephen G., E-mail: sdale@ucmerced.edu [Chemistry and Chemical Biology, School of Natural Sciences, University of California, Merced, 5200 North Lake Road, Merced, California 95343 (United States); Johnson, Erin R., E-mail: erin.johnson@dal.ca [Department of Chemistry, Dalhousie University, 6274 Coburg Road, Halifax, Nova Scotia B3H 4R2 (Canada)

    2015-11-14

    Exploration of the solvated electron phenomena using density-functional theory (DFT) generally results in prediction of a localised electron within an induced solvent cavity. However, it is well known that DFT favours highly delocalised charges, rendering the localisation of a solvated electron unexpected. We explore the origins of this counterintuitive behaviour using a model Kevan-structure system. When a polarisable-continuum solvent model is included, it forces electron localisation by introducing a strong energetic bias that favours integer charges. This results in the formation of a large energetic barrier for charge-hopping and can cause the self-consistent field to become trapped in local minima thus converging to stable solutions that are higher in energy than the ground electronic state. Finally, since the bias towards integer charges is caused by the polarisable continuum, these findings will also apply to other classical polarisation corrections, as in combined quantum mechanics and molecular mechanics (QM/MM) methods. The implications for systems beyond the solvated electron, including cationic DNA bases, are discussed.

  7. Effects of Energy Deposition Characteristics on Localised Forced Ignition of Homogeneous Mixtures

    Directory of Open Access Journals (Sweden)

    Dipal Patel

    2015-06-01

    Full Text Available The effects of the characteristic width of the energy deposition profile and the duration of energy deposition by the ignitor on localised forced ignition of stoichiometric and fuel-lean homogeneous mixtures have been analysed using simplified chemistry three-dimensional compressible Direct Numerical Simulation (DNS for different values of root-mean-square turbulent velocity fluctuation. The localised forced ignition is modelled using a source term in the energy transport equation, which deposits energy in a Gaussian manner from the centre of the ignitor over a stipulated period of time. It has been shown that the width of ignition energy deposition and the duration over which ignition energy is deposited have significant influences on the success of ignition and subsequent flame propagation. An increase in the width of ignition energy deposition (duration of energy deposition for a given amount of ignition energy has been found to have a detrimental effect on the ignition event, which may ultimately lead to misfire. Moreover, an increase in u′ gives rise to augmented heat transfer rate from the hot gas kernel, which in turn leads to a reduction in the extent of overall burning for both stoichiometric and fuel-lean homogeneous mixtures but the detrimental effects of high values of u′ on localised ignition are particularly prevalent for fuel-lean mixtures.

  8. Localised burst reconstruction from space-time PODs in a turbulent channel

    Science.gov (United States)

    Garcia-Gutierrez, Adrian; Jimenez, Javier

    2017-11-01

    The traditional proper orthogonal decomposition of the turbulent velocity fluctuations in a channel is extended to time under the assumption that the attractor is statistically stationary and can be treated as periodic for long-enough times. The objective is to extract space- and time-localised eddies that optimally represent the kinetic energy (and two-event correlation) of the flow. Using time-resolved data of a small-box simulation at Reτ = 1880 , minimal for y / h 0.25 , PODs are computed from the two-point spectral-density tensor Φ(kx ,kz , y ,y' , ω) . They are Fourier components in x, z and time, and depend on y and on the temporal frequency ω, or, equivalently, on the convection velocity c = ω /kx . Although the latter depends on y, a spatially and temporally localised `burst' can be synthesised by adding a range of PODs with specific phases. The results are localised bursts that are amplified and tilted, in a time-periodic version of Orr-like behaviour. Funded by the ERC COTURB project.

  9. An Autonomous Wearable System for Predicting and Detecting Localised Muscle Fatigue

    Directory of Open Access Journals (Sweden)

    Martin Colley

    2011-01-01

    Full Text Available Muscle fatigue is an established area of research and various types of muscle fatigue have been clinically investigated in order to fully understand the condition. This paper demonstrates a non-invasive technique used to automate the fatigue detection and prediction process. The system utilises the clinical aspects such as kinematics and surface electromyography (sEMG of an athlete during isometric contractions. Various signal analysis methods are used illustrating their applicability in real-time settings. This demonstrated system can be used in sports scenarios to promote muscle growth/performance or prevent injury. To date, research on localised muscle fatigue focuses on the clinical side and lacks the implementation for detecting/predicting localised muscle fatigue using an autonomous system. Results show that automating the process of localised muscle fatigue detection/prediction is promising. The autonomous fatigue system was tested on five individuals showing 90.37% accuracy on average of correct classification and an error of 4.35% in predicting the time to when fatigue will onset.

  10. Quantitative Evaluation of Stereo Visual Odometry for Autonomous Vessel Localisation in Inland Waterway Sensing Applications

    Directory of Open Access Journals (Sweden)

    Thomas Kriechbaumer

    2015-12-01

    Full Text Available Autonomous survey vessels can increase the efficiency and availability of wide-area river environment surveying as a tool for environment protection and conservation. A key challenge is the accurate localisation of the vessel, where bank-side vegetation or urban settlement preclude the conventional use of line-of-sight global navigation satellite systems (GNSS. In this paper, we evaluate unaided visual odometry, via an on-board stereo camera rig attached to the survey vessel, as a novel, low-cost localisation strategy. Feature-based and appearance-based visual odometry algorithms are implemented on a six degrees of freedom platform operating under guided motion, but stochastic variation in yaw, pitch and roll. Evaluation is based on a 663 m-long trajectory (>15,000 image frames and statistical error analysis against ground truth position from a target tracking tachymeter integrating electronic distance and angular measurements. The position error of the feature-based technique (mean of ±0.067 m is three times smaller than that of the appearance-based algorithm. From multi-variable statistical regression, we are able to attribute this error to the depth of tracked features from the camera in the scene and variations in platform yaw. Our findings inform effective strategies to enhance stereo visual localisation for the specific application of river monitoring.

  11. An Autonomous Wearable System for Predicting and Detecting Localised Muscle Fatigue

    Science.gov (United States)

    Al-Mulla, Mohamed R.; Sepulveda, Francisco; Colley, Martin

    2011-01-01

    Muscle fatigue is an established area of research and various types of muscle fatigue have been clinically investigated in order to fully understand the condition. This paper demonstrates a non-invasive technique used to automate the fatigue detection and prediction process. The system utilises the clinical aspects such as kinematics and surface electromyography (sEMG) of an athlete during isometric contractions. Various signal analysis methods are used illustrating their applicability in real-time settings. This demonstrated system can be used in sports scenarios to promote muscle growth/performance or prevent injury. To date, research on localised muscle fatigue focuses on the clinical side and lacks the implementation for detecting/predicting localised muscle fatigue using an autonomous system. Results show that automating the process of localised muscle fatigue detection/prediction is promising. The autonomous fatigue system was tested on five individuals showing 90.37% accuracy on average of correct classification and an error of 4.35% in predicting the time to when fatigue will onset. PMID:22319367

  12. From extended integrity monitoring to the safety evaluation of satellite-based localisation system

    International Nuclear Information System (INIS)

    Legrand, Cyril; Beugin, Julie; Marais, Juliette; Conrard, Blaise; El-Koursi, El-Miloudi; Berbineau, Marion

    2016-01-01

    Global Navigation Satellite Systems (GNSS) such as GPS, already used in aeronautics for safety-related applications, can play a major role in railway safety by allowing a train to locate itself safely. However, in order to implement this positioning solution in any embedded system, its performances must be evaluated according to railway standards. The evaluation of GNSS performances is not based on the same attributes class than RAMS evaluation. Face to these diffculties, we propose to express the integrity attribute, performance of satellite-based localisation. This attribute comes from aeronautical standards and for a hybridised GNSS with inertial system. To achieve this objective, the integrity attribute must be extended to this kind of system and algorithms initially devoted to GNSS integrity monitoring only must be adapted. Thereafter, the formalisation of this integrity attribute permits us to analyse the safety quantitatively through the probabilities of integrity risk and wrong-side failure. In this paper, after an introductory discussion about the use of localisation systems in railway safety context together with integrity issues, a particular integrity monitoring is proposed and described. The detection events of this algorithm permit us to conclude about safety level of satellite-based localisation system.

  13. TOR complex 2 localises to the cytokinetic actomyosin ring and controls the fidelity of cytokinesis.

    Science.gov (United States)

    Baker, Karen; Kirkham, Sara; Halova, Lenka; Atkin, Jane; Franz-Wachtel, Mirita; Cobley, David; Krug, Karsten; Maček, Boris; Mulvihill, Daniel P; Petersen, Janni

    2016-07-01

    The timing of cell division is controlled by the coupled regulation of growth and division. The target of rapamycin (TOR) signalling network synchronises these processes with the environmental setting. Here, we describe a novel interaction of the fission yeast TOR complex 2 (TORC2) with the cytokinetic actomyosin ring (CAR), and a novel role for TORC2 in regulating the timing and fidelity of cytokinesis. Disruption of TORC2 or its localisation results in defects in CAR morphology and constriction. We provide evidence that the myosin II protein Myp2 and the myosin V protein Myo51 play roles in recruiting TORC2 to the CAR. We show that Myp2 and TORC2 are co-dependent upon each other for their normal localisation to the cytokinetic machinery. We go on to show that TORC2-dependent phosphorylation of actin-capping protein 1 (Acp1, a known regulator of cytokinesis) controls CAR stability, modulates Acp1-Acp2 (the equivalent of the mammalian CAPZA-CAPZB) heterodimer formation and is essential for survival upon stress. Thus, TORC2 localisation to the CAR, and TORC2-dependent Acp1 phosphorylation contributes to timely control and the fidelity of cytokinesis and cell division. © 2016. Published by The Company of Biologists Ltd.

  14. Null stream analysis of Pulsar Timing Array data: localisation of resolvable gravitational wave sources

    Science.gov (United States)

    Goldstein, Janna; Veitch, John; Sesana, Alberto; Vecchio, Alberto

    2018-04-01

    Super-massive black hole binaries are expected to produce a gravitational wave (GW) signal in the nano-Hertz frequency band which may be detected by pulsar timing arrays (PTAs) in the coming years. The signal is composed of both stochastic and individually resolvable components. Here we develop a generic Bayesian method for the analysis of resolvable sources based on the construction of `null-streams' which cancel the part of the signal held in common for each pulsar (the Earth-term). For an array of N pulsars there are N - 2 independent null-streams that cancel the GW signal from a particular sky location. This method is applied to the localisation of quasi-circular binaries undergoing adiabatic inspiral. We carry out a systematic investigation of the scaling of the localisation accuracy with signal strength and number of pulsars in the PTA. Additionally, we find that source sky localisation with the International PTA data release one is vastly superior than what is achieved by its constituent regional PTAs.

  15. The impact of bladder preparation protocols on post treatment toxicity in radiotherapy for localised prostate cancer patients

    Directory of Open Access Journals (Sweden)

    Yat Man Tsang

    2017-09-01

    Conclusion: The empty bladder preparation approach has non-inferior acute and intermediate post RT GI and GU toxicities in patients treated for localised prostate cancer with advanced radiotherapy techniques compared to the full bladder preparation.

  16. Dismantling reified African culture through localised homosexualities in Uganda.

    Science.gov (United States)

    Nyanzi, Stella

    2013-01-01

    Uganda's Anti-Homosexuality Bill of 2009 aimed at protecting the cherished culture of the people against emergent threats to the traditional heterosexual family. The Bill's justification, however, lay in myopic imaginings of a homogenous African-ness and pedestrian oblivion to pluralities within African sexualities. This paper revisits the debate that homosexuality is 'un-African'. Rhetoric analysis of the Anti-Homosexuality Bill exposes how dominant discourses of law, medicine, religion, geography and culture reinforce the view that homosexuality is foreign to Africa. Based on ethnography in contemporary Uganda, I explore how self-identified same-sex-loving individuals simultaneously claim their African-ness and their homosexuality. Their strategies include ethnic belonging, membership to kinship structures, making connections with pre-colonial histories of homosexuality, civic participation in democratic processes, national identity, organising of lesbian, gay, bisexual, transgender, intersex and questioning support groups, language and nomenclature, visibility and voice in local communal activities, solidarity and adherence to cultural rituals. In present-day Uganda, same-sex-loving men, women and transgender people variously assert their African-ness.

  17. Localisation of epileptic foci using novel imaging modalities

    Science.gov (United States)

    De Ciantis, Alessio; Lemieux, Louis

    2013-01-01

    Purpose of review This review examines recent reports on the use of advanced techniques to map the regions and networks involved during focal epileptic seizure generation in humans. Recent findings A number of imaging techniques are capable of providing new localizing information on the ictal processes and epileptogenic zone. Evaluating the clinical utility of these findings has been mainly performed through post-hoc comparison with the findings of invasive EEG and ictal single-photon emission computed tomography, using postsurgical seizure reduction as the main outcome measure. Added value has been demonstrated in MRI-negative cases. Improved understanding of the human ictiogenic processes and the focus vs. network hypothesis is likely to result from the application of multimodal techniques that combine electrophysiological, semiological, and whole-brain coverage of brain activity changes. Summary On the basis of recent research in the field of neuroimaging, several novel imaging modalities have been improved and developed to provide information about the localization of epileptic foci. PMID:23823464

  18. Mechanism and function of Vav1 localisation in TCR signalling.

    Science.gov (United States)

    Ksionda, Olga; Saveliev, Alexander; Köchl, Robert; Rapley, Jonathan; Faroudi, Mustapha; Smith-Garvin, Jennifer E; Wülfing, Christoph; Rittinger, Katrin; Carter, Tom; Tybulewicz, Victor L J

    2012-11-15

    The antigen-specific binding of T cells to antigen presenting cells results in recruitment of signalling proteins to microclusters at the cell-cell interface known as the immunological synapse (IS). The Vav1 guanine nucleotide exchange factor plays a critical role in T cell antigen receptor (TCR) signalling, leading to the activation of multiple pathways. We now show that it is recruited to microclusters and to the IS in primary CD4(+) and CD8(+) T cells. Furthermore, we show that this recruitment depends on the SH2 and C-terminal SH3 (SH3(B)) domains of Vav1, and on phosphotyrosines 112 and 128 of the SLP76 adaptor protein. Biophysical measurements show that Vav1 binds directly to these residues on SLP76 and that efficient binding depends on the SH2 and SH3(B) domains of Vav1. Finally, we show that the same two domains are critical for the phosphorylation of Vav1 and its signalling function in TCR-induced calcium flux. We propose that Vav1 is recruited to the IS by binding to SLP76 and that this interaction is critical for the transduction of signals leading to calcium flux.

  19. The future for electrocoagulation as a localised water treatment technology.

    Science.gov (United States)

    Holt, Peter K; Barton, Geoffrey W; Mitchell, Cynthia A

    2005-04-01

    Electrocoagulation is an electrochemical method of treating polluted water whereby sacrificial anodes corrode to release active coagulant precursors (usually aluminium or iron cations) into solution. Accompanying electrolytic reactions evolve gas (usually as hydrogen bubbles) at the cathode. Electrocoagulation has a long history as a water treatment technology having been employed to remove a wide range of pollutants. However electrocoagulation has never become accepted as a 'mainstream' water treatment technology. The lack of a systematic approach to electrocoagulation reactor design/operation and the issue of electrode reliability (particularly passivation of the electrodes over time) have limited its implementation. However recent technical improvements combined with a growing need for small-scale decentralised water treatment facilities have led to a re-evaluation of electrocoagulation. Starting with a review of electrocoagulation reactor design/operation, this article examines and identifies a conceptual framework for electrocoagulation that focuses on the interactions between electrochemistry, coagulation and flotation. In addition detailed experimental data are provided from a batch reactor system removing suspended solids together with a mathematical analysis based on the 'white water' model for the dissolved air flotation process. Current density is identified as the key operational parameter influencing which pollutant removal mechanism dominates. The conclusion is drawn that electrocoagulation has a future as a decentralised water treatment technology. A conceptual framework is presented for future research directed towards a more mechanistic understanding of the process.

  20. A rare case of localised pigmented villonodular synovitis in the knee of a 24-year-old female soccer player

    DEFF Research Database (Denmark)

    Falster, Casper; Stockmann Poulsen, Simon; Joergensen, Uffe

    2017-01-01

    Localised pigmented villonodular synovitis (PVNS) of the knee is a rare diagnosis, with clinical signs and symptoms mimicking meniscal damage or other common knee injuries. We report the case of a 24-year-old female soccer player, seeking treatment after 7 months of persisting knee pain...... analyses confirmed the diagnosis of localised PVNS. The patient was subsequently free of symptoms with no signs of recurrence on MRI and had resumed soccer practice at the 1-year follow-up appointment....

  1. Development of a prototype of the tele-localisation system in radiotherapy using personal digital assistant via wireless communication.

    Science.gov (United States)

    Wu, Vincent Wing-Cheung; Tang, Fuk-hay; Cheung, Wai-kwan; Chan, Kit-chi

    2013-02-01

    In localisation of radiotherapy treatment field, the oncologist is present at the simulator to approve treatment details produced by the therapist. Problems may arise if the oncologist is not available and the patient requires urgent treatment. The development of a tele-localisation system is a potential solution, where the oncologist uses a personal digital assistant (PDA) to localise the treatment field on the image sent from the simulator through wireless communication and returns the information to the therapist after his or her approval. Our team developed the first tele-localisation prototype, which consisted of a server workstation (simulator) for the administration of digital imaging and communication in medicine localisation images including viewing and communication with the PDA via a Wi-Fi network; a PDA (oncologist's site) installed with the custom-built programme that synchronises with the server workstation and performs treatment field editing. Trial tests on accuracy and speed of the prototype system were conducted on 30 subjects with the treatment regions covering the neck, skull, chest and pelvis. The average time required in performing the localisation using the PDA was less than 1.5 min, with the blocked field longer than the open field. The transmission speed of the four treatment regions was similar. The average physical distortion of the images was within 4.4% and the accuracy of field size indication was within 5.3%. Compared with the manual method, the tele-localisation system presented with an average deviation of 5.5%. The prototype system fulfilled the planned objectives of tele-localisation procedure with reasonable speed and accuracy. © 2012 The Authors. Journal of Medical Imaging and Radiation Oncology © 2012 The Royal Australian and New Zealand College of Radiologists.

  2. A role for Na+,K+-ATPase α1 in regulating Rab27a localisation on melanosomes.

    Directory of Open Access Journals (Sweden)

    Antonia E G Booth

    Full Text Available The mechanism(s by which Rab GTPases are specifically recruited to distinct intracellular membranes remains elusive. Here we used Rab27a localisation onto melanosomes as a model to investigate Rab targeting. We identified the α1 subunit of Na+,K+-ATPase (ATP1a1 as a novel Rab27a interacting protein in melanocytes and showed that this interaction is direct with the intracellular M4M5 loop of ATP1a1 and independent of nucleotide bound status of the Rab. Knockdown studies in melanocytes revealed that ATP1a1 plays an essential role in Rab27a-dependent melanosome transport. Specifically, expression of ATP1a1, like the Rab27a GDP/GTP exchange factor (Rab3GEP, is essential for targeting and activation of Rab27a to melanosomes. Finally, we showed that the ability of Rab27a mutants to target to melanosomes correlates with the efficiency of their interaction with ATP1a1. Altogether these studies point to a new role for ATP1a1 as a regulator of Rab27a targeting and activation.

  3. Subcellular localisation of BAG-1 and its regulation of vitamin D receptor-mediated transactivation and involucrin expression in oral keratinocytes: Implications for oral carcinogenesis

    International Nuclear Information System (INIS)

    Lee, San San; Crabb, Simon J.; Janghra, Nari; Carlberg, Carsten; Williams, Ann C.; Cutress, Ramsey I.; Packham, Graham; Hague, Angela

    2007-01-01

    In oral cancers, cytoplasmic BAG-1 overexpression is a marker of poor prognosis. BAG-1 regulates cellular growth, differentiation and survival through interactions with diverse proteins, including the vitamin D receptor (VDR), a key regulator of keratinocyte growth and differentiation. BAG-1 is expressed ubiquitously in human cells as three major isoforms of 50 kDa (BAG-1L), 46 kDa (BAG-1M) and 36 kDa (BAG-1S) from a single mRNA. In oral keratinocytes BAG-1L, but not BAG-1M and BAG-1S, enhanced VDR transactivation in response to 1α,25-dihydroxyvitamin D 3. BAG-1L was nucleoplasmic and nucleolar, whereas BAG-1S and BAG-1M were cytoplasmic and nucleoplasmic in localisation. Having identified the nucleolar localisation sequence in BAG-1L, we showed that mutation of this sequence did not prevent BAG-1L from potentiating VDR activity. BAG-1L also potentiated transactivation of known vitamin-D-responsive gene promoters, osteocalcin and 24-hydroxylase, and enhanced VDR-dependent transcription and protein expression of the keratinocyte differentiation marker, involucrin. These results demonstrate endogenous gene regulation by BAG-1L by potentiating nuclear hormone receptor function and suggest a role for BAG-1L in 24-hydroxylase regulation of vitamin D metabolism and the cellular response of oral keratinocytes to 1α,25-dihydroxyvitamin D 3 . By contrast to the cytoplasmic BAG-1 isoforms, BAG-1L may act to suppress tumorigenesis

  4. Audit of preoperative localisation of tumor with tattoo for patients undergoing laparoscopic colorectal surgery.

    Science.gov (United States)

    Saleh, A; Ihedioha, U; Babu, B; Evans, J; Kang, P

    2016-08-01

    Preoperative localisation of tumour is an essential requirement in laparoscopic colorectal surgery. Since the introduction of laparoscopic colorectal resections in NGH in February 2010, the difficulties of tumour localisation at the time of surgery without tattoo have been highlighted. Furthermore, endoscopic documentation of site of tattoo with respect to the tumour can be inconsistent and at times misleading or difficult to interpret. Tattooing guidelines should be simple to follow and consistent for all lesions irrespective of the location of the tumour. The recommendations were to place at least three spots of tattoo one mucosal fold distal to the lesion and clearly document site of tattoo with respect to tumour in the endoscopy report. We identified 100 patients undergoing elective laparoscopic colorectal cancer resections over a two-year period. Data were collected regarding presence of tattoo preoperatively as documented in the colonoscopy report and subsequently the visibility of the tattoo at time of laparoscopy and its accuracy in relation to the tumour. Abdominoperineal resections and emergency colorectal operations were excluded. Only 59% of the patients had a visible and accurate tattoo. In 17% of the patients, the tattoo was not visible at all, although it was documented in the endoscopy report that it had been administered. In 4% of patients, it was visible but inaccurately placed. In 20% of the patients, there were no tattoos at all, necessitating on table endoscopy and intraoperative specimen analysis to confirm that the tumour/lesion was within the resection specimen. Preoperative tumour localisation is extremely important to correctly identify the site of tumour or lesion at laparoscopy. A standardised departmental protocol should be implemented by all endoscopists to place three spots of tattoo one mucosal fold distal to any significant lesions found. Failure to tattoo lesions/cancers preoperatively can lead to intraoperative delays and

  5. Effects of fuel Lewis number on localised forced ignition of turbulent homogeneous mixtures: A numerical investigation

    Directory of Open Access Journals (Sweden)

    Dipal Patel

    2016-09-01

    Full Text Available The influences of fuel Lewis number LeF (ranging from 0.8 to 1.2 on localised forced ignition and early stages of combustion of stoichiometric and fuel-lean homogeneous mixtures have been analysed using simple chemistry three-dimensional compressible direct numerical simulations for different values of root-mean-square velocity fluctuation and the energy deposition characteristics (i.e. characteristic width and the duration of energy deposition by the ignitor. The localised forced ignition is modelled using a source term in the energy transport equation, which deposits energy in a Gaussian manner from the centre of the ignitor over a stipulated period of time. The fuel Lewis number LeF has been found to have significant influences on the extent of burning of stoichiometric and fuel-lean homogeneous mixtures. It has been shown that the width of ignition energy deposition and the duration over which the ignition energy is deposited have significant influences on the success of ignition and subsequent flame propagation. An increase in the width of ignition energy deposition and the duration of energy deposition for a given amount of ignition energy have been found to have detrimental effects on the ignition event, which may ultimately lead to misfire. For a given value of u' (LeF, the rate of heat transfer from the hot gas kernel increases with increasing LeF (u', which in turn leads to a reduction in the extent of overall burning for both stoichiometric and fuel-lean homogeneous mixtures but the detrimental effects of high values of u' on localised forced ignition are particularly prevalent for fuel-lean mixtures. Detailed physical explanations have been provided for the observed LeF,u' and energy deposition characteristics effects.

  6. EphB4 localises to the nucleus of prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Mertens-Walker, Inga, E-mail: inga.mertenswalker@qut.edu.au [Institute of Health and Biomedical Innovation, Queensland University of Technology, Woolloongabba, QLD (Australia); Australian Prostate Cancer Research Centre—Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba 4102, QLD (Australia); Lisle, Jessica E. [Institute of Health and Biomedical Innovation, Queensland University of Technology, Woolloongabba, QLD (Australia); Australian Prostate Cancer Research Centre—Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba 4102, QLD (Australia); Nyberg, William A. [Institute of Health and Biomedical Innovation, Queensland University of Technology, Woolloongabba, QLD (Australia); Stephens, Carson R. [Institute of Health and Biomedical Innovation, Queensland University of Technology, Woolloongabba, QLD (Australia); Australian Prostate Cancer Research Centre—Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba 4102, QLD (Australia); Burke, Leslie [Institute of Health and Biomedical Innovation, Queensland University of Technology, Woolloongabba, QLD (Australia); Rutkowski, Raphael; Herington, Adrian C.; Stephenson, Sally-Anne [Institute of Health and Biomedical Innovation, Queensland University of Technology, Woolloongabba, QLD (Australia); Australian Prostate Cancer Research Centre—Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba 4102, QLD (Australia)

    2015-04-10

    The EphB4 receptor tyrosine kinase is over-expressed in a variety of different epithelial cancers including prostate where it has been shown to be involved in survival, migration and angiogenesis. We report here that EphB4 also resides in the nucleus of prostate cancer cell lines. We used in silico methods to identify a bipartite nuclear localisation signal (NLS) in the extracellular domain and a monopartite NLS sequence in the intracellular kinase domain of EphB4. To determine whether both putative NLS sequences were functional, fragments of the EphB4 sequence containing each NLS were cloned to create EphB4NLS-GFP fusion proteins. Localisation of both NLS-GFP proteins to the nuclei of transfected cells was observed, demonstrating that EphB4 contains two functional NLS sequences. Mutation of the key amino residues in both NLS sequences resulted in diminished nuclear accumulation. As nuclear translocation is often dependent on importins we confirmed that EphB4 and importin-α can interact. To assess if nuclear EphB4 could be implicated in gene regulatory functions potential EphB4-binding genomic loci were identified using chromatin immunoprecipitation and Lef1 was confirmed as a potential target of EphB4-mediated gene regulation. These novel findings add further complexity to the biology of this important cancer-associated receptor. - Highlights: • The EphB4 protein can be found in the nucleus of prostate cancer cell lines. • EphB4 contains two functional nuclear localisation signals. • Chromatin immunoprecipitation has identified potential genome sequences to which EphB4 binds. • Lef1 is a confirmed target for EphB4-mediated gene regulation.

  7. EphB4 localises to the nucleus of prostate cancer cells

    International Nuclear Information System (INIS)

    Mertens-Walker, Inga; Lisle, Jessica E.; Nyberg, William A.; Stephens, Carson R.; Burke, Leslie; Rutkowski, Raphael; Herington, Adrian C.; Stephenson, Sally-Anne

    2015-01-01

    The EphB4 receptor tyrosine kinase is over-expressed in a variety of different epithelial cancers including prostate where it has been shown to be involved in survival, migration and angiogenesis. We report here that EphB4 also resides in the nucleus of prostate cancer cell lines. We used in silico methods to identify a bipartite nuclear localisation signal (NLS) in the extracellular domain and a monopartite NLS sequence in the intracellular kinase domain of EphB4. To determine whether both putative NLS sequences were functional, fragments of the EphB4 sequence containing each NLS were cloned to create EphB4NLS-GFP fusion proteins. Localisation of both NLS-GFP proteins to the nuclei of transfected cells was observed, demonstrating that EphB4 contains two functional NLS sequences. Mutation of the key amino residues in both NLS sequences resulted in diminished nuclear accumulation. As nuclear translocation is often dependent on importins we confirmed that EphB4 and importin-α can interact. To assess if nuclear EphB4 could be implicated in gene regulatory functions potential EphB4-binding genomic loci were identified using chromatin immunoprecipitation and Lef1 was confirmed as a potential target of EphB4-mediated gene regulation. These novel findings add further complexity to the biology of this important cancer-associated receptor. - Highlights: • The EphB4 protein can be found in the nucleus of prostate cancer cell lines. • EphB4 contains two functional nuclear localisation signals. • Chromatin immunoprecipitation has identified potential genome sequences to which EphB4 binds. • Lef1 is a confirmed target for EphB4-mediated gene regulation

  8. Fault kinematics and localised inversion within the Troms-Finnmark Fault Complex, SW Barents Sea

    Science.gov (United States)

    Zervas, I.; Omosanya, K. O.; Lippard, S. J.; Johansen, S. E.

    2018-04-01

    The areas bounding the Troms-Finnmark Fault Complex are affected by complex tectonic evolution. In this work, the history of fault growth, reactivation, and inversion of major faults in the Troms-Finnmark Fault Complex and the Ringvassøy Loppa Fault Complex is interpreted from three-dimensional seismic data, structural maps and fault displacement plots. Our results reveal eight normal faults bounding rotated fault blocks in the Troms-Finnmark Fault Complex. Both the throw-depth and displacement-distance plots show that the faults exhibit complex configurations of lateral and vertical segmentation with varied profiles. Some of the faults were reactivated by dip-linkages during the Late Jurassic and exhibit polycyclic fault growth, including radial, syn-sedimentary, and hybrid propagation. Localised positive inversion is the main mechanism of fault reactivation occurring at the Troms-Finnmark Fault Complex. The observed structural styles include folds associated with extensional faults, folded growth wedges and inverted depocentres. Localised inversion was intermittent with rifting during the Middle Jurassic-Early Cretaceous at the boundaries of the Troms-Finnmark Fault Complex to the Finnmark Platform. Additionally, tectonic inversion was more intense at the boundaries of the two fault complexes, affecting Middle Triassic to Early Cretaceous strata. Our study shows that localised folding is either a product of compressional forces or of lateral movements in the Troms-Finnmark Fault Complex. Regional stresses due to the uplift in the Loppa High and halokinesis in the Tromsø Basin are likely additional causes of inversion in the Troms-Finnmark Fault Complex.

  9. Extremely low frequency electromagnetic fields promote mesenchymal stem cell migration by increasing intracellular Ca2+ and activating the FAK/Rho GTPases signaling pathways in vitro.

    Science.gov (United States)

    Zhang, Yingchi; Yan, Jiyuan; Xu, Haoran; Yang, Yong; Li, Wenkai; Wu, Hua; Liu, Chaoxu

    2018-05-21

    The ability of mesenchymal stem cells (MSCs) to migrate to the desired tissues or lesions is crucial for stem cell-based regenerative medicine and tissue engineering. Optimal therapeutics for promoting MSC migration are expected to become an effective means for tissue regeneration. Electromagnetic fields (EMF), as a noninvasive therapy, can cause a lot of biological changes in MSCs. However, whether EMF can promote MSC migration has not yet been reported. We evaluated the effects of EMF on cell migration in human bone marrow-derived MSCs. With the use of Helmholtz coils and an EMF stimulator, 7.5, 15, 30, 50, and 70 Hz/1 mT EMF was generated. Additionally, we employed the L-type calcium channel blocker verapamil and the focal adhesion kinase (FAK) inhibitor PF-573228 to investigate the role of intracellular calcium content, cell adhesion proteins, and the Rho GTPase protein family (RhoA, Rac1, and Cdc42) in EMF-mediated MSC migration. Cell adhesion proteins (FAK, talin, and vinculin) were detected by Western blot analysis. The Rho GTPase protein family activities were assessed by G-LISA, and F-actin levels, which reflect actin cytoskeletal organization, were detected using immunofluorescence. All the 7.5, 15, 30, 50, and 70 Hz/1 mT EMF promoted MSC migration. EMF increased MSC migration in an intracellular calcium-dependent manner. Notably, EMF-enhanced migration was mediated by FAK activation, which was critical for the formation of focal contacts, as evidenced by increased talin and vinculin expression. Moreover, RhoA, Rac1, and Cdc42 were activated by FAK to increase cytoskeletal organization, thus promoting cell contraction. EMF promoted MSC migration by increasing intracellular calcium and activating the FAK/Rho GTPase signaling pathways. This study provides insights into the mechanisms of MSC migration and will enable the rational design of targeted therapies to improve MSC engraftment.

  10. Evc is a positive mediator of Ihh-regulated bone growth that localises at the base of chondrocyte cilia.

    Science.gov (United States)

    Ruiz-Perez, Victor L; Blair, Helen J; Rodriguez-Andres, M Elena; Blanco, Maria Jose; Wilson, Amy; Liu, Yu-Ning; Miles, Colin; Peters, Heiko; Goodship, Judith A

    2007-08-01

    EVC is a novel protein mutated in the human chondroectodermal dysplasia Ellis-van Creveld syndrome (EvC; OMIM: 225500). We have inactivated Evc in the mouse and show that Evc(-/-) mice develop an EvC-like syndrome, including short ribs, short limbs and dental abnormalities. lacZ driven by the Evc promoter revealed that Evc is expressed in the developing bones and the orofacial region. Antibodies developed against Evc locate the protein at the base of the primary cilium. The growth plate of Evc(-/-) mice shows delayed bone collar formation and advanced maturation of chondrocytes. Indian hedgehog (Ihh) is expressed normally in the growth plates of Evc(-/-) mice, but expression of the Ihh downstream genes Ptch1 and Gli1 was markedly decreased. Recent studies have shown that Smo localises to primary cilia and that Gli3 processing is defective in intraflagellar transport mutants. In vitro studies using Evc(-/-) cells demonstrate that the defect lies downstream of Smo. Chondrocyte cilia are present in Evc(-/-) mice and Gli3 processing appears normal by western blot analysis. We conclude that Evc is an intracellular component of the hedgehog signal transduction pathway that is required for normal transcriptional activation of Ihh target genes.

  11. Localisation of 3H-GABA in the rat olfactory bulb: An in vivo and in vitro autoradiographic study

    International Nuclear Information System (INIS)

    Jaffe, E.H.; Cuello, A.C.; Priestley, J.V.

    1983-01-01

    In an attempt to further clarify the localisation of GABAergic elements in the olfactory bulb we have performed, in vivo and in vitro, autoradiographic studies with 3 H-GABA (#betta#-amino butyric acid) and 3 H-DABA (L-2,4 diamino butyric acid). The results have shown a strong labelling with 3 H-GABA of the glial cells in all the layers of the olfactory bulb. A high concentration of grains was observed in the periglomerular region. The labelling in the external plexiform layer was uniformly distributed in the neuropile with the strongest activity at the level of the dendritic processes of the granule cells, leaving the mitral cell dendrites and cell bodies almost free of grains. 3 H-DABA showed a very similar pattern to 3 H-GABA. When olfactory bulb slices were preincubated with #betta#-alanine the labelling of the glial elements almost disappeared especially at the level of the olfactory nerve layer. The labelling pattern of the other layers of the bulb remained mostly unchanged. This supports the view that a population of periglomerular and granule cells are GABAergic and that #betta#-alanine competes with GABA uptake sites only in glial cells. (orig.)

  12. A prognostic profile of hypoxia-induced genes for localised high-grade soft tissue sarcoma

    DEFF Research Database (Denmark)

    Aggerholm-Pedersen, Ninna; Sørensen, Brita Singers; Overgaard, Jens

    2016-01-01

    sarcoma (STS). METHODS: The hypoxia-induced gene quantification was performed by real-time quantitative PCR (RT-qPCR) of formalin-fixed, paraffin-embedded tissue samples. The gene expression cut-points were determined in a test cohort of 55 STS patients and used to allocate each patient into a more......BACKGROUND: For decades, tumour hypoxia has been pursued as a cancer treatment target. However, prognostic and predictive biomarkers are essential for the use of this target in the clinic. This study investigates the prognostic value of a hypoxia-induced gene profile in localised soft tissue...

  13. Les facteurs de localisation d’un nouveau type d’établissements tertiaires : les datacentres

    Directory of Open Access Journals (Sweden)

    Henry Bakis

    2015-02-01

    Full Text Available Les centres de traitement de données ou datacentres (data centers sont de nouveaux types d’établissements tertiaires rendus nécessaires par suite du développement d’Internet (sites web, cloud. Ils assurent notamment l’hébergement de serveurs (housing d’entreprises ou de particuliers en location ou colocation d’espaces. Cet article tente de présenter ce type d’établissements tertiaires et de mettre l’accent sur leurs enjeux en termes de localisation et d’environnement. Il met notamment l’accent sur leur consommation énergétique.

  14. Immunoelectron microscopic localisation of keratin and luminal epithelial antigens in normal and neoplastic urothelium.

    Science.gov (United States)

    Wilson, P D; Nathrath, W B; Trejdosiewicz, L K

    1982-01-01

    Immunoelectron microscope cytochemistry was carried out on 2% paraformaldehyde fixed, 50 mu sections of normal urothelium and bladder carcinoma cells in culture using antisera raised in rabbits to human 40-63 000 MW epidermal "broad spectrum" keratin and calf urothelial "luminal epithelial antigen" (aLEA) Both the unconjugated and indirect immunoperoxidase-DAB techniques were used before routine embedding. The localisation of both keratin and luminal epithelial antigen (LEA) was similar in normal and neoplastic cells and reaction product was associated not only with tonofilaments but also lining membrane vesicles and on fine filaments in the cytoplasmic ground substance.

  15. Localisation d'une source sonore par un réseau de microphones

    OpenAIRE

    Thaljaoui , Adel; Brulin , Damien; Val , Thierry; Nasri , Nejah

    2014-01-01

    National audience; L'assistance à domicile d'une personne âgée, notamment la connaissance de sa position géographique en tout instant, est devenue actuellement l'une des problématiques les plus urgentes. L'exploitation de l'information audio captée par un réseau de capteurs munis de microphones constitue un axe de recherche prometteur qui pourrait contribuer à une meilleure localisation dans le cadre des maisons intelligentes. Nous introduisons, dans cet article, nos premiers travaux sur la l...

  16. Mesenteric vein thrombosis after percitaneous transhepatic portal vein catheterisation for the localisation of an insulinoma

    International Nuclear Information System (INIS)

    Luska, G.; Langer, H.E.; Le Blanc, S.; Medizinische Hochschule Hannover

    1984-01-01

    The authors report on a fatal mesenteric vein thrombosis following an uncomplicated percutaneous transhepatic portal vein catheterisation for the localisation of an insulinoma. Several hours after the procedure the patient developed an acute abdomen. An emergency laparotomy revealed a haemorrhagic infarct of the ileum. The resected specimen showed an acute phlebitis with fresh thrombus. The cause of the phlebothrombosis was thought to be intimal damage from high osmolar contrast medium. There was no evidence of damage due to the catheder, either on the phlebogram or pathologically. (orig.) [de

  17. Robust localisation of automated guided vehicles for computer-integrated manufacturing environments

    Directory of Open Access Journals (Sweden)

    Dixon, R. C.

    2013-05-01

    Full Text Available As industry moves toward an era of complete automation and mass customisation, automated guided vehicles (AGVs are used as material handling systems. However, the current techniques that provide navigation, control, and manoeuvrability of automated guided vehicles threaten to create bottlenecks and inefficiencies in manufacturing environments that strive towards the optimisation of part production. This paper proposes a decentralised localisation technique for an automated guided vehicle without any non-holonomic constraints. Incorporation of these vehicles into the material handling system of a computer-integrated manufacturing environment would increase the characteristics of robustness, efficiency, flexibility, and advanced manoeuvrability.

  18. Fibre Tip Sensors for Localised Temperature Sensing Based on Rare Earth-Doped Glass Coatings

    Directory of Open Access Journals (Sweden)

    Erik P. Schartner

    2014-11-01

    Full Text Available We report the development of a point temperature sensor, based on monitoring upconversion emission from erbium:ytterbium-doped tellurite coatings on the tips of optical fibres. The dip coating technique allows multiple sensors to be fabricated simultaneously, while confining the temperature-sensitive region to a localised region on the end-face of the fibre. The strong response of the rare earth ions to changing temperature allows a resolution of 0.1–0.3 °C to be recorded over the biologically relevant range of temperatures from 23–39 °C.

  19. Subdiffraction field localisation in the scattering of femtosecond laser radiation by a dielectric microsphere

    Energy Technology Data Exchange (ETDEWEB)

    Geints, Yu E; Zemlyanov, A A; Panina, E K [V.E. Zuev Institute of Atmospheric Optics, Siberian Branch, Russian Academy of Sciences, Tomsk (Russian Federation)

    2014-01-31

    The time dynamics of the optical field was theoretically considered in the near-field diffraction zone in the scattering of a femtosecond laser pulse by a transparent spherical microparticle. The spatial region of field focusing by the particle (the 'photonic jet' zone) was investigated; the evolution of the jet shape and the peak intensity in this region were analysed. For the first time it was determined that an extremely tight optical field localisation to a subdiffraction size is possible at a certain (resonance) temporal stage of photonic jet development. (radiation scattering)

  20. Evaluation of an automatic MR-based gold fiducial marker localisation method for MR-only prostate radiotherapy

    Science.gov (United States)

    Maspero, Matteo; van den Berg, Cornelis A. T.; Zijlstra, Frank; Sikkes, Gonda G.; de Boer, Hans C. J.; Meijer, Gert J.; Kerkmeijer, Linda G. W.; Viergever, Max A.; Lagendijk, Jan J. W.; Seevinck, Peter R.

    2017-10-01

    An MR-only radiotherapy planning (RTP) workflow would reduce the cost, radiation exposure and uncertainties introduced by CT-MRI registrations. In the case of prostate treatment, one of the remaining challenges currently holding back the implementation of an RTP workflow is the MR-based localisation of intraprostatic gold fiducial markers (FMs), which is crucial for accurate patient positioning. Currently, MR-based FM localisation is clinically performed manually. This is sub-optimal, as manual interaction increases the workload. Attempts to perform automatic FM detection often rely on being able to detect signal voids induced by the FMs in magnitude images. However, signal voids may not always be sufficiently specific, hampering accurate and robust automatic FM localisation. Here, we present an approach that aims at automatic MR-based FM localisation. This method is based on template matching using a library of simulated complex-valued templates, and exploiting the behaviour of the complex MR signal in the vicinity of the FM. Clinical evaluation was performed on seventeen prostate cancer patients undergoing external beam radiotherapy treatment. Automatic MR-based FM localisation was compared to manual MR-based and semi-automatic CT-based localisation (the current gold standard) in terms of detection rate and the spatial accuracy and precision of localisation. The proposed method correctly detected all three FMs in 15/17 patients. The spatial accuracy (mean) and precision (STD) were 0.9 mm and 0.5 mm respectively, which is below the voxel size of 1.1 × 1.1 × 1.2 mm3 and comparable to MR-based manual localisation. FM localisation failed (3/51 FMs) in the presence of bleeding or calcifications in the direct vicinity of the FM. The method was found to be spatially accurate and precise, which is essential for clinical use. To overcome any missed detection, we envision the use of the proposed method along with verification by an observer. This will result in a

  1. Evaluation of an automatic MR-based gold fiducial marker localisation method for MR-only prostate radiotherapy.

    Science.gov (United States)

    Maspero, Matteo; van den Berg, Cornelis A T; Zijlstra, Frank; Sikkes, Gonda G; de Boer, Hans C J; Meijer, Gert J; Kerkmeijer, Linda G W; Viergever, Max A; Lagendijk, Jan J W; Seevinck, Peter R

    2017-10-03

    An MR-only radiotherapy planning (RTP) workflow would reduce the cost, radiation exposure and uncertainties introduced by CT-MRI registrations. In the case of prostate treatment, one of the remaining challenges currently holding back the implementation of an RTP workflow is the MR-based localisation of intraprostatic gold fiducial markers (FMs), which is crucial for accurate patient positioning. Currently, MR-based FM localisation is clinically performed manually. This is sub-optimal, as manual interaction increases the workload. Attempts to perform automatic FM detection often rely on being able to detect signal voids induced by the FMs in magnitude images. However, signal voids may not always be sufficiently specific, hampering accurate and robust automatic FM localisation. Here, we present an approach that aims at automatic MR-based FM localisation. This method is based on template matching using a library of simulated complex-valued templates, and exploiting the behaviour of the complex MR signal in the vicinity of the FM. Clinical evaluation was performed on seventeen prostate cancer patients undergoing external beam radiotherapy treatment. Automatic MR-based FM localisation was compared to manual MR-based and semi-automatic CT-based localisation (the current gold standard) in terms of detection rate and the spatial accuracy and precision of localisation. The proposed method correctly detected all three FMs in 15/17 patients. The spatial accuracy (mean) and precision (STD) were 0.9 mm and 0.5 mm respectively, which is below the voxel size of [Formula: see text] mm 3 and comparable to MR-based manual localisation. FM localisation failed (3/51 FMs) in the presence of bleeding or calcifications in the direct vicinity of the FM. The method was found to be spatially accurate and precise, which is essential for clinical use. To overcome any missed detection, we envision the use of the proposed method along with verification by an observer. This will result in a

  2. Resonant photoluminescence studies of carrier localisation in c-plane InGaN/GaN quantum well structures

    Science.gov (United States)

    Blenkhorn, W. E.; Schulz, S.; Tanner, D. S. P.; Oliver, R. A.; Kappers, M. J.; Humphreys, C. J.; Dawson, P.

    2018-05-01

    In this paper we report on changes in the form of the low temperature (12 K) photoluminescence spectra of an InGaN/GaN quantum well structure as a function of excitation photon energy. As the photon energy is progressively reduced we observe at a critical energy a change in the form of the spectra from one which is determined by the occupation of the complete distribution of hole localisation centres to one which is determined by the resonant excitation of specific localisation sites. This change is governed by an effective mobility edge whereby the photo-excited holes remain localised at their initial energy and are prevented from scattering to other localisation sites. This assignment is confirmed by the results of atomistic tight binding calculations which show that the wave function overlap of the lowest lying localised holes with other hole states is low compared with the overlap of higher lying hole states with other higher lying hole states.

  3. Co-localisation studies of Arabidopsis SR splicing factors reveal different types of speckles in plant cell nuclei

    International Nuclear Information System (INIS)

    Lorkovic, Zdravko J.; Hilscher, Julia; Barta, Andrea

    2008-01-01

    SR proteins are multidomain splicing factors which are important for spliceosome assembly and for regulation of alternative splicing. In mammalian nuclei these proteins localise to speckles from where they are recruited to transcription sites. By using fluorescent protein fusion technology and different experimental approaches it has been shown that Arabidopsis SR proteins, in addition to diffuse nucleoplasmic staining, localise into an irregular nucleoplasmic network resembling speckles in mammalian cells. As Arabidopsis SR proteins fall into seven conserved sub-families we investigated co-localisation of members of the different sub-families in transiently transformed tobacco protoplast. Here we demonstrate the new finding that members of different SR protein sub-families localise into distinct populations of nuclear speckles with no, partial or complete co-localisation. This is particularly interesting as we also show that these proteins do interact in a yeast two-hybrid assay as well as in pull-down and in co-immunopreciptiation assays. Our data raise the interesting possibility that SR proteins are partitioned into distinct populations of nuclear speckles to allow a more specific recruitment to the transcription/pre-mRNA processing sites of particular genes depending on cell type and developmental stage

  4. Interleukin 10 in Helicobacter pylori associated gastritis: immunohistochemical localisation and in vitro effects on cytokine secretion

    Science.gov (United States)

    Bodger, K; Bromelow, K; Wyatt, J; Heatley, R

    2001-01-01

    Background/Aims—Interleukin 10 (IL-10) is a counterinflammatory peptide implicated in the downregulation of human intestinal immune responses. Enhanced secretion of IL-10 has been documented in gastric biopsy organ culture in Helicobacter pylori infection. This study aimed to define the cellular origins of IL-10 in H pylori associated gastritis, and to determine the effects of endogenous IL-10 on proinflammatory cytokine secretion in vitro. Methods—Endoscopic biopsies were obtained from the gastric antrum at endoscopy from patients with dyspepsia. Two pairs of antral biopsies were cultured in vitro for 24 hours, one pair in the presence of neutralising anti-IL-10 monoclonal antibody, the other pair as controls. The cytokine content of culture supernatants (tumour necrosis factor α (TNF-α), IL-6, and IL-8) was determined by enzyme linked immunosorbent assay and corrected for biopsy weight. Helicobacter pylori status was established by histology and biopsy urease test, and histopathology graded by the Sydney system. In a subgroup of patients, western blotting was used to establish CagA serological status. Immunohistochemistry for IL-10 was performed on formalin fixed tissues using a combination of microwave antigen retrieval and the indirect avidin–biotin technique. Immunoreactivity was scored semiquantitatively. Results—In vitro culture was performed in 41 patients: 31 with H pylori positive chronic gastritis and 10 H pylori negative. In vitro secretion of TNF-α, IL-6, and IL-8 for "control" biopsies was significantly higher in H pylori positive versus negative samples, with values of TNF-α and IL-6 correlating with the degree of active and chronic inflammation and being higher in CagA seropositive cases. No evidence for enhanced cytokine secretion was seen in biopsies cocultured in the presence of anti-IL-10 monoclonal antibody. Immunohistochemistry was performed in 29 patients, of whom 13 were H pylori positive. IL-10 immunoreactivity was observed in

  5. Detection and cellular localisation of the synthetic soluble macromolecular drug carrier pHPMA

    Energy Technology Data Exchange (ETDEWEB)

    Kissel, Maria; Peschke, Peter; Strunz, Anke M.; Kuehnlein, Rainer; Debus, Juergen [Department of Radiation Oncology, E0505, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Subr, Vladimir; Ulbrich, Karel [Institute of Macromolecular Chemistry, Prague (Czech Republic); Friedrich, Eckhard [Division of Biology, University of Koblenz-Landau, Landau (Germany)

    2002-08-01

    Synthetic macromolecules such as copolymers of N-(2-hydroxypropyl)methacrylamide (pHPMA) are potential carriers for the delivery of drugs owing to their ability to passively accumulate in solid tumours [enhanced permeation and retention (EPR) effect]. To gain further knowledge about the biodistribution and the cellular localisation, poly(HPMA) was prepared for labelling by introducing biotin molecules. Biotinylated pHPMA (5 mol%) was intravenously injected into tumour-bearing rats and the accumulation of biotin-pHPMA was visualised using a streptavidin-alkaline phosphatase technique at day 7 post injection. In spite of the high solubility of pHPMA copolymers and the lack of attachment to cell structures, the biotinylated polymer could be easily detected in tissues fixed in 10% paraformaldehyde-phosphate buffer at 4 C for 48 h. While biotin-pHPMA could be detected intracytoplasmically in liver and spleen, a predominantly interstitial localisation was observed within the anaplastic prostate carcinoma (Dunning R3327-AT1). How biotin as a label influences the biodistribution of poly(HPMA) was assessed by scintigraphy, autoradiography and histology comparing homopolymer poly(HPMA) with biotin-pHPMA. The organ distribution patterns of the two polymers correlated well, except with respect to kidney. It is assumed that the accumulation of biotin-pHPMA in the distal tubuli is due to a biotin transporter in the brush border membrane. The technique presented is useful for a more comprehensive understanding of the biodistribution of soluble macromolecules. (orig.)

  6. Fear of new or recurrent melanoma after treatment for localised melanoma.

    Science.gov (United States)

    Bell, Katy J L; Mehta, Yachna; Turner, Robin M; Morton, Rachael L; Dieng, Mbathio; Saw, Robyn; Guitera, Pascale; McCaffery, Kirsten; Low, Donald; Low, Cynthia; Jenkins, Marisa; Irwig, Les; Webster, Angela C

    2017-11-01

    To estimate the amount of fear of new or recurrent melanoma among people treated for localised melanoma in an Australian specialist centre. We randomly selected 400 potential participants from all those treated for localised melanoma at the Melanoma Institute Australia during 2014 (n = 902). They were asked to complete an adapted version of the Fear of Cancer Recurrence Inventory (FCRI). We calculated summary statistics for demographics, clinical variables and total FCRI and subscale scores. Two hundred fifteen people (54%) completed the FCRI questionnaire. The overall mean severity subscale score was 15.0 (95% CI 14.0-16.1). A high proportion of participants had scores above a proposed threshold to screen for clinical fear of cancer recurrence (77% and 63% of participants with and without new or recurrent melanoma had severity subscale scores ≥13). Most participants also had scores above a threshold found to have high specificity for clinical fear of cancer recurrence (65% and 48% of participants with and without new or recurrent melanoma had severity subscale scores ≥16). The severity subscale appeared to discriminate well between groups with differing levels of risk of new or recurrent melanoma. There is a substantial amount of fear of new or recurrent melanoma among this population, despite most having a very good prognosis. Copyright © 2017 John Wiley & Sons, Ltd.

  7. Reliability of horizontal and vertical tube shift techniques in the localisation of supernumerary teeth.

    Science.gov (United States)

    Mallineni, S K; Anthonappa, R P; King, N M

    2016-12-01

    To assess the reliability of the vertical tube shift technique (VTST) and horizontal tube shift technique (HTST) for the localisation of unerupted supernumerary teeth (ST) in the anterior region of the maxilla. A convenience sample of 83 patients who attended a major teaching hospital because of unerupted ST was selected. Only non-syndromic patients with ST and who had complete clinical and radiographic and surgical records were included in the study. Ten examiners independently rated the paired set of radiographs for each technique. Chi-square test, paired t test and kappa statistics were employed to assess the intra- and inter-examiner reliability. Paired sets of 1660 radiographs (830 pairs for each technique) were available for the analysis. The overall sensitivity for VTST and HTST was 80.6 and 72.1% respectively, with slight inter-examiner and good intra-examiner reliability. Statistically significant differences were evident between the two localisation techniques (p HTST in the anterior region of the maxilla.

  8. The Reduction of Vertical Interchannel Crosstalk: The Analysis of Localisation Thresholds for Natural Sound Sources

    Directory of Open Access Journals (Sweden)

    Rory Wallis

    2017-03-01

    Full Text Available In subjective listening tests, natural sound sources were presented to subjects as vertically-oriented phantom images from two layers of loudspeakers, ‘height’ and ‘main’. Subjects were required to reduce the amplitude of the height layer until the position of the resultant sound source matched that of the same source presented from the main layer only (the localisation threshold. Delays of 0, 1 and 10 ms were applied to the height layer with respect to the main, with vertical stereophonic and quadraphonic conditions being tested. The results of the study showed that the localisation thresholds obtained were not significantly affected by sound source or presentation method. Instead, the only variable whose effect was significant was interchannel time difference (ICTD. For ICTD of 0 ms, the median threshold was −9.5 dB, which was significantly lower than the −7 dB found for both 1 and 10 ms. The results of the study have implications both for the recording of sound sources for three-dimensional (3D audio reproduction formats and also for the rendering of 3D images.

  9. Localised proton magnetic resonance spectroscopy of the brain after perinatal hypoxia: a preliminary report

    International Nuclear Information System (INIS)

    Chateil, J.F.; Quesson, B.; Thiaudiere, E.; Delalande, C.; Canioni, P.; Brun, M.; Diard, F.; Sarlangue, J.; Billeaud, C.

    1999-01-01

    Objectives. Perinatal hypoxic ischaemic injury is a significant cause of neurodevelopmental impairment. The aim of this study was to evaluate localised proton magnetic resonance spectroscopy ( 1 H-MRS) after birth asphyxia. Materials and methods. Thirty newborn infants suspected of having perinatal asphyxia (Apgar score 1 H-MRS was recorded in a single voxel, localised in white matter, using a STEAM sequence. Results. Image quality was good in 25 of 30 babies. 1 H-MRS was performed in 19 of 30 subjects, with adequate quality in 16. Choline, creatine/phosphocreatine and N-acetylaspartate peaks and peak-area ratios were analysed. Lactate was detected in four infants. The N-acetylaspartate/choline ratio was lower in infants with an impaired neurological outcome, but the difference was not statistically significant. Conclusions. This study suggests that 1 H-MRS may be useful for assessing cerebral metabolism in the neonate. A raised lactate level and decreased N-acetylaspartate/choline ratio may be predictive of a poor outcome. However, in our experience this method is limited by the difficulty in performing the examination during the first hours after birth in critically ill babies, the problems related to use of a monovoxel sequence, the dispersion of the ratios and the lack of determination of the absolute concentration of the metabolites. (orig.)

  10. Multi-particle Anderson Localisation: Induction on the Number of Particles

    International Nuclear Information System (INIS)

    Chulaevsky, Victor; Suhov, Yuri

    2009-01-01

    This paper is a follow-up of our recent papers Chulaevsky and Suhov (Commun Math Phys 283:479-489, 2008) and Chulaevsky and Suhov (Commun Math Phys in press, 2009) covering the two-particle Anderson model. Here we establish the phenomenon of Anderson localisation for a quantum N-particle system on a lattice with short-range interaction and in presence of an IID external potential with sufficiently regular marginal cumulative distribution function (CDF). Our main method is an adaptation of the multi-scale analysis (MSA; cf. Froehlich and Spencer, Commun Math Phys 88:151-184, 1983; Froehlich et al., Commun Math Phys 101:21-46, 1985; von Dreifus and Klein, Commun Math Phys 124:285-299, 1989) to multi-particle systems, in combination with an induction on the number of particles, as was proposed in our earlier manuscript (Chulaevsky and Suhov 2007). Recently, Aizenman and Warzel (2008) proved spectral and dynamical localisation for N-particle lattice systems with a short-range interaction, using an extension of the Fractional-Moment Method (FMM) developed earlier for single-particle models in Aizenman and Molchanov (Commun Math Phys 157:245-278, 1993) and Aizenman et al. (Commun Math Phys 224:219-253, 2001) (see also references therein) which is also combined with an induction on the number of particles

  11. Aseptic necrosis at multiple localisations in a lupus patient with lymphoma.

    Science.gov (United States)

    Bazso, A; Bazso, T; Szodoray, P; Poor, G; Kiss, E

    2014-04-01

    Avascular or aseptic necrosis is a well-defined entity leading to the degradation of cellular elements of the bone. The pathogenesis of osteonecrosis (ON) is still unknown. There are two main types of ON: traumatic or non-traumatic. Several clinical entities could associate with ON, systemic diseases, environmental factors, pregnancy, systemic autoimmune or rheumatic diseases, thrombophilia, corticosteroid therapy, cytotoxic dugs, infections, metabolic and hematologic diseases, etc. Corticosteroids (CS) are still the most frequently used therapeutic options in the early phase and during flares of these diseases. Inflammatory cytokines and antibodies have been described to participate in the pathogenesis of ON. The infiltrative disorders of the bone marrow could also contribute to the development of ON. Hereby, we describe a female patient with NHL followed by SLE in whom ON has developed at least in two localisations. Lupus flare, long-term CS therapy, lymphoma relapse or the presence of antiphospholipid antibodies were excluded. Although the bi-localised ON could be contributed to immunologic factors or trauma, the exact aetiology in this case could not be elucidated.

  12. A Review of Non-Invasive Techniques to Detect and Predict Localised Muscle Fatigue

    Directory of Open Access Journals (Sweden)

    Mohamed R. Al-Mulla

    2011-03-01

    Full Text Available Muscle fatigue is an established area of research and various types of muscle fatigue have been investigated in order to fully understand the condition. This paper gives an overview of the various non-invasive techniques available for use in automated fatigue detection, such as mechanomyography, electromyography, near-infrared spectroscopy and ultrasound for both isometric and non-isometric contractions. Various signal analysis methods are compared by illustrating their applicability in real-time settings. This paper will be of interest to researchers who wish to select the most appropriate methodology for research on muscle fatigue detection or prediction, or for the development of devices that can be used in, e.g., sports scenarios to improve performance or prevent injury. To date, research on localised muscle fatigue focuses mainly on the clinical side. There is very little research carried out on the implementation of detecting/predicting fatigue using an autonomous system, although recent research on automating the process of localised muscle fatigue detection/prediction shows promising results.

  13. A Review of Non-Invasive Techniques to Detect and Predict Localised Muscle Fatigue

    Science.gov (United States)

    Al-Mulla, Mohamed R.; Sepulveda, Francisco; Colley, Martin

    2011-01-01

    Muscle fatigue is an established area of research and various types of muscle fatigue have been investigated in order to fully understand the condition. This paper gives an overview of the various non-invasive techniques available for use in automated fatigue detection, such as mechanomyography, electromyography, near-infrared spectroscopy and ultrasound for both isometric and non-isometric contractions. Various signal analysis methods are compared by illustrating their applicability in real-time settings. This paper will be of interest to researchers who wish to select the most appropriate methodology for research on muscle fatigue detection or prediction, or for the development of devices that can be used in, e.g., sports scenarios to improve performance or prevent injury. To date, research on localised muscle fatigue focuses mainly on the clinical side. There is very little research carried out on the implementation of detecting/predicting fatigue using an autonomous system, although recent research on automating the process of localised muscle fatigue detection/prediction shows promising results. PMID:22163810

  14. A Case of Definitive Therapy for Localised Prostate Cancer: Report of a Urological Nightmare

    Directory of Open Access Journals (Sweden)

    Andreas Sommerhuber

    2012-01-01

    Full Text Available Radical prostatectomy, external beam radiotherapy and permanent brachytherapy are the most common treatment options for nonmetastatic localised adenocarcinoma of the prostate (PCa. Accurate pretherapeutic clinical staging is difficult, the number of positive cores after biopsy does not imperatively represent the extension of the cancer. Furthermore postoperative upgrading in Gleason score is frequently observed. Even in a localised setting a certain amount of patients with organ-confined PCa will develop biochemical progression. In case of a rise in PSA level after radiation the majority of patients will receive androgen deprivation therapy what must be considered as palliative. If local or systemic progressive disease is associated with evolving neuroendocrine differentiation hormonal manipulation is increasingly ineffective; radiotherapy and systemic chemotherapy with a platinum agent and etoposide are recommended. In case of local progression complications such as pelvic pain, gross haematuria, infravesical obstruction and rectal invasion with obstruction and consecutive ileus can possibly occur. In this situation palliative radical surgery is a therapy option especially in the absence of distant metastases. A case with local and later systemic progression after permanent brachytherapy is presented here.

  15. Detection and cellular localisation of the synthetic soluble macromolecular drug carrier pHPMA

    International Nuclear Information System (INIS)

    Kissel, Maria; Peschke, Peter; Strunz, Anke M.; Kuehnlein, Rainer; Debus, Juergen; Subr, Vladimir; Ulbrich, Karel; Friedrich, Eckhard

    2002-01-01

    Synthetic macromolecules such as copolymers of N-(2-hydroxypropyl)methacrylamide (pHPMA) are potential carriers for the delivery of drugs owing to their ability to passively accumulate in solid tumours [enhanced permeation and retention (EPR) effect]. To gain further knowledge about the biodistribution and the cellular localisation, poly(HPMA) was prepared for labelling by introducing biotin molecules. Biotinylated pHPMA (5 mol%) was intravenously injected into tumour-bearing rats and the accumulation of biotin-pHPMA was visualised using a streptavidin-alkaline phosphatase technique at day 7 post injection. In spite of the high solubility of pHPMA copolymers and the lack of attachment to cell structures, the biotinylated polymer could be easily detected in tissues fixed in 10% paraformaldehyde-phosphate buffer at 4 C for 48 h. While biotin-pHPMA could be detected intracytoplasmically in liver and spleen, a predominantly interstitial localisation was observed within the anaplastic prostate carcinoma (Dunning R3327-AT1). How biotin as a label influences the biodistribution of poly(HPMA) was assessed by scintigraphy, autoradiography and histology comparing homopolymer poly(HPMA) with biotin-pHPMA. The organ distribution patterns of the two polymers correlated well, except with respect to kidney. It is assumed that the accumulation of biotin-pHPMA in the distal tubuli is due to a biotin transporter in the brush border membrane. The technique presented is useful for a more comprehensive understanding of the biodistribution of soluble macromolecules. (orig.)

  16. Localised in vivo 1H spectroscopy of human bone and soft tissue tumours

    International Nuclear Information System (INIS)

    Bongers, H.; Schick, F.; Skalej, M.; Hess, C.F.; Jung, W.I.

    1992-01-01

    Localised 1 H in vivo magnetic resonance spectroscopy was applied to fibrous and bone tumours before and during cytostatic treatment and radiotherapy. The results of 24 studies in 18 patients with malignant tumours of the leg or pelvis are presented including cases of sarcoma, malignant fibrous histiocytoma, multiple myeloma, malignant lymphoma and metastasis. A double spin echo localisation method with water suppression was implemented on a 1.5 Tesla whole body unit. Voxel size was (13 mm) 3 or (20 mm) 3 . The most common resonances besides lipids (16/18) were those of choline (10/18) and creatine (5/18). Creatine was always decreased in comparison to choline and often absent from tumour spectra. Additional resonances with phase distorsions from J-coupling (chemical shift region 1.8-2.5 and 2.2-4.0 ppm) were recorded. In the presence of lipids, lactate remained undetectable because special editing techniques were not available. Significant spectral differences between different tumour types were not evident. In about 30% of the investigations the spectra contained only water and lipid signals. Follow-up studies in three patients during radio- and chemotherapy showed a decrease in metabolites (choline, creatine, unassigned signals between 1.0 and 2.5 ppm) after weeks and months. The decrease in choline was most pronounced paralleled by an increase in lipid/choline ratios. (orig.)

  17. Organisation as a key factor in Localised Agri-Food Systems (LAFS

    Directory of Open Access Journals (Sweden)

    Corrado Giacomini

    2015-05-01

    Full Text Available Most studies of Localised Agri-Food Systems (LAFS focus on the localised concentration of members and firms, and pay less attention to organisational factors, particularly those of an exogenous nature. This paper focuses on the role of organisation in a LAFS, assessing the efficacy of EU organisational measures aimed at strengthening the concentration of supply from the recent CAP reform 2014-2020. The paper has three sections. Part One describes the evolution of the concept of LAFS. Part Two examines the leading role played by institutions in organising relationships between firms in a LAFS. The example provided is that of the measures affecting the organisation of supply introduced by the recent CAP reform, 2014-2020. It makes particular reference to the Distretto del pomodoro da industria – Nord Italia (‘Industrial Tomato District – Northern Italy’. Part Three describes how organisational factors can lead to the creation of a LAFS, while the criterion of proximity is necessary but not sufficient.

  18. Prediction of three-dimensional residual stresses at localised indentations in pipes

    International Nuclear Information System (INIS)

    Hyde, T.H.; Luo, R.; Becker, A.A.

    2012-01-01

    Residual stresses are investigated using Finite Element (FE) analyses at localised indentations in pipes with and without internal pressures due to reverse plasticity caused by springback of the surrounding material after removal of the indenter. The indentation loading is applied via rigid 3D short indenters. The effects of the residual indentation depth, internal pressure, indenter size and different material properties on the residual stresses for different pipes have been investigated by carrying out parametric sensitivity studies. In order to predict the residual stresses, empirical formulations have been developed, which show a good correlation with the FE for residual stresses for pipes with diameter to thickness ratios of 35–72. - Highlights: ► A comprehensive elastic–plastic FE analysis of residual stresses caused by localised pipe indentations is presented. ► The effects of residual indentation depth, internal pressure, indenter size and material properties have been studied. ► Empirical formulations have been developed, which show a good correlation with the FE for residual stresses for pipes with diameter to thickness ratios of 35–72.

  19. Energy confinement and MHD activity in shaped TCV plasmas with localised electron cyclotron heating

    International Nuclear Information System (INIS)

    Pochelon, A.; Alberti, S.; Angioni, C.

    2001-01-01

    Confinement in TCV (Tokamak a Configuration Variable) EC heated discharges is studied as a function of plasma shape, i.e. as a function of elongation 1.1<κ<2.15 and triangularity -0.65≤δ≤0.5. The electron energy confinement time is found to increase with elongation, in part due to the increase of plasma current with elongation. The beneficial effect of negative triangularities is most effective at low power and tends to reduce at the higher powers used. The large variety of sawtooth types observed in TCV for different power deposition locations from on axis to the q=1 region can be simulated with a model including a local power deposition, a growing m/n=1 island (convection and reconnection), plasma rotation and finite heat diffusivity across flux surfaces. (author)

  20. Development and localisation of casemix applications for inpatient hospital activity in EU member states.

    Science.gov (United States)

    Wiley, M M

    1999-01-01

    The successful infiltration of casemix techniques across geographical, systemic and cultural boundaries provides an interesting and timely example of the translation of research evidence into health policy development. This paper explores the specifics of this policy development by reviewing the application of casemix techniques within the acute hospital systems of European Union member states. The fact that experimentation with or application of casemix measures can be reported for the majority of European Union member states would suggest that the deployment of these measures can be expected to continue to expand within these health systems into the new millennium.

  1. Fukunaga-Koontz feature transformation for statistical structural damage detection and hierarchical neuro-fuzzy damage localisation

    Science.gov (United States)

    Hoell, Simon; Omenzetter, Piotr

    2017-07-01

    Considering jointly damage sensitive features (DSFs) of signals recorded by multiple sensors, applying advanced transformations to these DSFs and assessing systematically their contribution to damage detectability and localisation can significantly enhance the performance of structural health monitoring systems. This philosophy is explored here for partial autocorrelation coefficients (PACCs) of acceleration responses. They are interrogated with the help of the linear discriminant analysis based on the Fukunaga-Koontz transformation using datasets of the healthy and selected reference damage states. Then, a simple but efficient fast forward selection procedure is applied to rank the DSF components with respect to statistical distance measures specialised for either damage detection or localisation. For the damage detection task, the optimal feature subsets are identified based on the statistical hypothesis testing. For damage localisation, a hierarchical neuro-fuzzy tool is developed that uses the DSF ranking to establish its own optimal architecture. The proposed approaches are evaluated experimentally on data from non-destructively simulated damage in a laboratory scale wind turbine blade. The results support our claim of being able to enhance damage detectability and localisation performance by transforming and optimally selecting DSFs. It is demonstrated that the optimally selected PACCs from multiple sensors or their Fukunaga-Koontz transformed versions can not only improve the detectability of damage via statistical hypothesis testing but also increase the accuracy of damage localisation when used as inputs into a hierarchical neuro-fuzzy network. Furthermore, the computational effort of employing these advanced soft computing models for damage localisation can be significantly reduced by using transformed DSFs.

  2. Several adaptor proteins promote intracellular localisation of the transporter MRP4/ABCC4 in platelets and haematopoietic cells.

    Science.gov (United States)

    Schaletzki, Yvonne; Kromrey, Marie-Luise; Bröderdorf, Susanne; Hammer, Elke; Grube, Markus; Hagen, Paul; Sucic, Sonja; Freissmuth, Michael; Völker, Uwe; Greinacher, Andreas; Rauch, Bernhard H; Kroemer, Heyo K; Jedlitschky, Gabriele

    2017-01-05

    The multidrug resistance protein 4 (MRP4/ABCC4) has been identified as an important transporter for signalling molecules including cyclic nucleotides and several lipid mediators in platelets and may thus represent a novel target to interfere with platelet function. Besides its localisation in the plasma membrane, MRP4 has been also detected in the membrane of dense granules in resting platelets. In polarised cells it is localised at the basolateral or apical plasma membrane. To date, the mechanism of MRP4 trafficking has not been elucidated; protein interactions may regulate both the localisation and function of this transporter. We approached this issue by searching for interacting proteins by in vitro binding assays, followed by immunoblotting and mass spectrometry, and by visualising their co-localisation in platelets and haematopoietic cells. We identified the PDZ domain containing scaffold proteins ezrin-binding protein 50 (EBP50/NHERF1), postsynaptic density protein 95 (PSD95), and sorting nexin 27 (SNX27), but also the adaptor protein complex 3 subunit β3A (AP3B1) and the heat shock protein HSP90 as putative interaction partners of MRP4. The knock-down of SNX27, PSD95, and AP3B1 by siRNA in megakaryoblastic leukaemia cells led to a redistribution of MRP4 from intracellular structures to the plasma membrane. Inhibition of HSP90 led to a diminished expression and retention of MRP4 in the endoplasmic reticulum. These results indicate that MRP4 localisation and function are regulated by multiple protein interactions. Changes in the adaptor proteins can hence lead to altered localisation and function of the transporter.

  3. Evaluation of specimen preparation techniques for micro-PIXE localisation of elements in hyperaccumulating plants

    International Nuclear Information System (INIS)

    Kachenko, Anthony G.; Siegele, Rainer; Bhatia, Naveen P.; Singh, Balwant; Ionescu, Mihail

    2008-01-01

    Hybanthus floribundus subsp. floribundus, a rare Australian Ni-hyperaccumulating shrub and Pityrogramma calomelanos var. austroamericana, an Australian naturalized As-hyperaccumulating fern are promising species for use in phytoremediation of contaminated sites. Micro-proton-induced X-ray emission (μ-PIXE) spectroscopy was used to map the elemental distribution of the accumulated metal(loid)s, Ca and K in leaf or pinnule tissues of the two plant species. Samples were prepared by two contrasting specimen preparation techniques: freeze-substitution in tetrahydrofuran (THF) and freeze-drying. The specimens were analysed to compare the suitability of each technique in preserving (i) the spatial elemental distribution and (ii) the tissue structure of the specimens. Further, the μ-PIXE results were compared with concentration of elements in the bulk tissue obtained by ICP-AES analysis. In H. floribundus subsp. floribundus, μ-PIXE analysis revealed Ni, Ca and K concentrations in freeze-dried leaf tissues were at par with bulk tissue concentrations. Elemental distribution maps illustrated that Ni was preferentially localised in the adaxial epidermal tissues (1% DW) and least concentration was found in spongy mesophyll tissues (0.53% DW). Conversely, elemental distribution maps of THF freeze-substituted tissues indicated significantly lower Ni, Ca and K concentrations than freeze-dried specimens and bulk tissue concentrations. Moreover, Ni concentrations were uniform across the whole specimen and no localisation was observed. In P. calomelanos var. austroamericana freeze-dried pinnule tissues, μ-PIXE revealed statistically similar As, Ca and K concentrations as compared to bulk tissue concentrations. Elemental distribution maps showed that As localisation was relatively uniform across the whole specimen. Once again, THF freeze-substituted tissues revealed a significant loss of As compared to freeze-dried specimens and the concentrations obtained by bulk tissue analysis

  4. Primary treatments for clinically localised prostate cancer: a comprehensive lifetime cost-utility analysis.

    Science.gov (United States)

    Cooperberg, Matthew R; Ramakrishna, Naren R; Duff, Steven B; Hughes, Kathleen E; Sadownik, Sara; Smith, Joseph A; Tewari, Ashutosh K

    2013-03-01

    WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Multiple treatment alternatives exist for localised prostate cancer, with few high-quality studies directly comparing their comparative effectiveness and costs. The present study is the most comprehensive cost-effectiveness analysis to date for localised prostate cancer, conducted with a lifetime horizon and accounting for survival, health-related quality-of-life, and cost impact of secondary treatments and other downstream events, as well as primary treatment choices. The analysis found minor differences, generally slightly favouring surgical methods, in quality-adjusted life years across treatment options. However, radiation therapy (RT) was consistently more expensive than surgery, and some alternatives, e.g. intensity-modulated RT for low-risk disease, were dominated - that is, both more expensive and less effective than competing alternatives. To characterise the costs and outcomes associated with radical prostatectomy (open, laparoscopic, or robot-assisted) and radiation therapy (RT: dose-escalated three-dimensional conformal RT, intensity-modulated RT, brachytherapy, or combination), using a comprehensive, lifetime decision analytical model. A Markov model was constructed to follow hypothetical men with low-, intermediate-, and high-risk prostate cancer over their lifetimes after primary treatment; probabilities of outcomes were based on an exhaustive literature search yielding 232 unique publications. In each Markov cycle, patients could have remission, recurrence, salvage treatment, metastasis, death from prostate cancer, and death from other causes. Utilities for each health state were determined, and disutilities were applied for complications and toxicities of treatment. Costs were determined from the USA payer perspective, with incorporation of patient costs in a sensitivity analysis. Differences across treatments in quality-adjusted life years across methods were modest, ranging from 10.3 to

  5. Clinical experience with a new stereotactic localisation method for fractionated radiotherapy of extracranial lesions

    International Nuclear Information System (INIS)

    Engenhart-Cabillic, R.; Pastyr, O.; Wenz, F.; Debus, J.; Schlegel, W.; Bahner, M.L.; Wannenmacher, M.

    1996-01-01

    Purpose/Objective: Effectiveness of radiotherapy in terms of local control has been shown to be linked with treatment accuracy. Conformal radiation therapy outside the brain maybe limited by relative inaccuracy of positioning and repositioning uncertainty during treatment planning, simulation and radiotherapy. It has been shown that stereotactic localisation methods provide an excellent localisation accuracy for intracranial lesions. The aim of this study was to develop a stereotactic system for the whole body and to test the feasibility in a clinical study. Materials and Method: The system includes a reversible stereotactic patient fixation, localization and positioning system which can be used during CT-imaging for simulation and for treatment. The target volume and adjacent critical structures were outlined for treatment three dimensional planning and the coordinates of the target point were calculated. The overall accuracy of target localization including soft and hardware inaccuracy was measured by a phantom. Three patients with spinal and paraspinal tumors were treated by conventionally fractionated high precision megavoltage radiotherapy with this system. The treatment time was 6 weeks in each patients. The stereotactic coordinates of anatomical landmarks as well as implanted fiducals were measured by CT-imaging, X-ray localization and electronic portal imaging at 20 different paraspinal localisations. Stereotactic CT-imaging was performed for treatment planning and once a week during treatment. Results: Standard deviation of stereotactic coordinats in the phantom was 0.5 mm in the lateral direction (x), 1.0 mm in the cranio-caudal orientation (z) and 1.2 mm in the dorso-ventral orientation. About 60 minutes are required to immobilise the patient properly for the first set-up and the subsequent daily set-up time during therapy was 10 min. In patients a total of 18 CT examination and 56 portal images have been analysed. The mean variation of the stereotactic

  6. Study of the possibility of localising a channel instability in Forsmark-1

    International Nuclear Information System (INIS)

    Karlsson, J.K-H.; Pazsit, I.

    1998-01-01

    A special type of instability occurred in the Swedish BWR Forsmark 1 in 1996. In contrast to the better known global or regional instabilities, the decay ratio appeared to be very high in one half of the core and quite low in the other half. A more detailed analysis showed that the most likely reason for the observed behaviour is a local perturbation of thermohydraulic character induced by the incorrect positioning of a fuel assembly. In such a case it is of importance to determine the position of the unseated assembly already during operation so that it can be easily found during reloading. The subject of this paper is to report on development and application of a method by which the position of such a local perturbation can be determined. The method can be separated into two parts that support and complement each other. First a visualisation technique was elaborated which displays the space-time behaviour of the neutron flux oscillations in the core. This visualisation expedites a very good qualitative comprehension of the situation and can be useful for the operators. It also gives a basis for the application of the localisation algorithm. Second, a quantitative localisation method, based on reactor physical models of the perturbation and of the transfer function between the perturbation and the flux oscillations, was elaborated. This latter takes noise spectra from selected detectors as input and yields the perturbation position as output. The strength of the method lies in its potentially high spatial resolution, which is smaller than the typical distance between two adjacent LPRM detectors. The method was tested on simulated data, and then applied to the Forsmark measurements. The location of the disturbance, found by the algorithm, is in accordance with independent judgements for the case, and close to a position where an unseated assembly was found during refuelling. The purpose of this study was to develop and test the localisation method. To apply the

  7. The effect of internal hydrogen on surface slip localisation on polycrystalline AISI 316L stainless steel

    International Nuclear Information System (INIS)

    Aubert, Isabelle; Olive, Jean-Marc; Saintier, Nicolas

    2010-01-01

    A statistical analysis of the effect of internal hydrogen on the surface slip morphology of relatively high nickel content AISI 316L type austenitic stainless steel was carried out on high resolution data obtained by atomic force microscopy. Surface plastic strain localisation was studied for different hydrogen contents, two grain sizes, and two plastic strain levels. The height and spacing of approximately 8000 slip bands, observed on 12 specimens, are shown to follow log-normal distributions. Hydrogen increased the mean slip-band height and the mean slip-band spacing for the two macroscopic plastic strain levels considered, and for the two hydrogen concentrations in coarse-grained specimens. The hydrogen effect was also observed for fine-grained specimens, but only for the highest hydrogen concentration. In addition, the emerging dislocation velocity increased by a factor 3 for high hydrogen content.

  8. Localisation of a neutron source using measurements and calculation of the neutron flux and its gradient

    CERN Document Server

    Linden, P; Dahl, B; Pázsit, I; Por, G

    1999-01-01

    We have performed laboratory measurements of the neutron flux and its gradient in a static model experiment, similar to a model problem proposed in Pazsit (Ann. Nucl. Energy 24 (1997) 1257). The experimental system consists of a radioactive neutron source located in a water tank. The measurements are performed using a recently developed very small optical fibre detector. The measured values of the flux and its gradient are then used to test the possibility of localising the source. The results show that it is possible to measure the flux on the circumference of a circle and from this calculate the flux gradient vector. Then, by comparison of the measured quantities with corresponding MCNP calculations, both the direction and the distance to the source are found and thus the position of the source can be determined.

  9. Localised perforation of locally advanced transverse colon cancer with spontaneous colocutaneous fistula formation: a clinical challenge.

    Science.gov (United States)

    Wadhwani, Nikita; Diwakar, Deepak Kumar

    2018-04-19

    Colon cancer can present with complications such as obstruction, perforation and bleeding. The clinical presentation has been recognised as an independent prognostic factor for morbidity and mortality. 1 We present a rare case of localised perforation of a locally advanced colon cancer arising from mid-transverse colon in an elderly woman in the absence of widely metastatic disease with eventual cutaneous involvement of the overlying skin by direct extension, resulting in formation of colocutaneous fistula. The management of such cases is complex as usually tailored to the situation encountered. 2 This case was a clinical challenge to choose between initial palliative resection and curative R0 resection following neoadjuvant chemotherapy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  10. Imaging cellular structures in super-resolution with SIM, STED and Localisation Microscopy: A practical comparison.

    Science.gov (United States)

    Wegel, Eva; Göhler, Antonia; Lagerholm, B Christoffer; Wainman, Alan; Uphoff, Stephan; Kaufmann, Rainer; Dobbie, Ian M

    2016-06-06

    Many biological questions require fluorescence microscopy with a resolution beyond the diffraction limit of light. Super-resolution methods such as Structured Illumination Microscopy (SIM), STimulated Emission Depletion (STED) microscopy and Single Molecule Localisation Microscopy (SMLM) enable an increase in image resolution beyond the classical diffraction-limit. Here, we compare the individual strengths and weaknesses of each technique by imaging a variety of different subcellular structures in fixed cells. We chose examples ranging from well separated vesicles to densely packed three dimensional filaments. We used quantitative and correlative analyses to assess the performance of SIM, STED and SMLM with the aim of establishing a rough guideline regarding the suitability for typical applications and to highlight pitfalls associated with the different techniques.

  11. Globalisation, localisation and implications of a transforming nursing workforce in New Zealand: opportunities and challenges.

    Science.gov (United States)

    Callister, Paul; Badkar, Juthika; Didham, Robert

    2011-09-01

    Severe staff and skill shortages within the health systems of developed countries have contributed to increased migration by health professionals. New Zealand stands out among countries in the Organisation for Economic Co-operation and Development in terms of the high level of movements in and out of the country of skilled professionals, including nurses. In New Zealand, much attention has been given to increasing the number of Māori and Pacific nurses as one mechanism for improving Māori and Pacific health. Against a backdrop of the changing characteristics of the New Zealand nursing workforce, this study demonstrates that the globalisation of the nursing workforce is increasing at a faster rate than its localisation (as measured by the growth of the Māori and New Zealand-born Pacific workforces in New Zealand). This challenges the implementation of culturally appropriate nursing programmes based on the matching of nurse and client ethnicities. © 2011 Blackwell Publishing Ltd.

  12. Localised surface plasmon-like resonance generated by microwave electromagnetic waves in pipe defects

    Science.gov (United States)

    Alobaidi, Wissam M.; Nima, Zeid A.; Sandgren, Eric

    2018-01-01

    Localised surface plasmon (LSP)-like resonance phenomena were simulated in COMSOL Multiphysics™, and the electric field enhancement was evaluated in eight pipe defects using the microwave band from 1.80 to 3.00 GHz and analysed by finite element analysis (FEA). The simulation was carried out, in each defect case, on a pipe that has 762 mm length and 152.4 mm inner diameter, and 12.7 mm pipe wall thickness. Defects were positioned in the middle of the pipe and were named as follows; SD: Square Defect, FCD: fillet corner defect, FD: fillet defect, HCD: half circle defect, TCD: triangle corner defect, TD: triangle defect, ZD: zigzag defect, GD: gear defect. The LSP electric field, and scattering parametric (S21, and S11) waves were evaluated in all cases and found to be strongly dependent on the size and the shape of the defect rather than the pipe and or the medium materials.

  13. Cellular localisation of the anti-cancer drug camptothecin in Camptotheca acuminata Decne (Nyssaceae

    Directory of Open Access Journals (Sweden)

    G Pasqua

    2009-06-01

    Full Text Available In Camptotheca acuminata, we studied the cellular sites of accumulation of the alkaloid camptothecin (CPT, in both plants grown in the field and those grown in a greenhouse, subjecting the latter to stress (i.e., draught, nutritional deficit, and pruning. Fresh sections of the leaf, stem, and root were analysed for the presence of CPT by examining the autofluorescence that the CPT molecule emits when exposed to UV radiation. In the plants grown in the field, CPT was observed only rarely. In the greenhouse plants, CPT had accumulated in crystalline form in the vacuole of specialised cells (i.e., segregator idioblasts, which were not morphologically distinguishable from the cells of the surrounding tissues. In the organs examined, the segregator idioblasts were localised in parenchymatic and epidermal tissues. CPT crystals were also detected in the glandular trichomes on both the stem and leaf.

  14. Three-dimensional sound localisation with a lizard peripheral auditory model

    DEFF Research Database (Denmark)

    Kjær Schmidt, Michael; Shaikh, Danish

    the networks learned a transfer function that translated the three-dimensional non-linear mapping into estimated azimuth and elevation values for the acoustic target. The neural network with two hidden layers as expected performed better than that with only one hidden layer. Our approach assumes that for any...... location of an acoustic target in three dimensions. Our approach utilises a model of the peripheral auditory system of lizards [Christensen-Dalsgaard and Manley 2005] coupled with a multi-layer perceptron neural network. The peripheral auditory model’s response to sound input encodes sound direction...... information in a single plane which by itself is insufficient to localise the acoustic target in three dimensions. A multi-layer perceptron neural network is used to combine two independent responses of the model, corresponding to two rotational movements, into an estimate of the sound direction in terms...

  15. Activation of Rho GTPases by Cytotoxic Necrotizing Factor 1 Induces Macropinocytosis and Scavenging Activity in Epithelial Cells

    Science.gov (United States)

    Fiorentini, Carla; Falzano, Loredana; Fabbri, Alessia; Stringaro, Annarita; Logozzi, Mariaantonia; Travaglione, Sara; Contamin, Stéphanette; Arancia, Giuseppe; Malorni, Walter; Fais, Stefano

    2001-01-01

    Macropinocytosis, a ruffling-driven process that allows the capture of large material, is an essential aspect of normal cell function. It can be either constitutive, as in professional phagocytes where it ends with the digestion of captured material, or induced, as in epithelial cells stimulated by growth factors. In this case, the internalized material recycles back to the cell surface. We herein show that activation of Rho GTPases by a bacterial protein toxin, the Escherichia coli cytotoxic necrotizing factor 1 (CNF1), allowed epithelial cells to engulf and digest apoptotic cells in a manner similar to that of professional phagocytes. In particular, we have demonstrated that 1) the activation of all Rho, Rac, and Cdc42 by CNF1 was essential for the capture and internalization of apoptotic cells; and 2) such activation allowed the discharge of macropinosomal content into Rab7 and lysosomal associated membrane protein-1 acidic lysosomal vesicles where the ingested particles underwent degradation. Taken together, these findings indicate that CNF1-induced “switching on” of Rho GTPases may induce in epithelial cells a scavenging activity, comparable to that exerted by professional phagocytes. The activation of such activity in epithelial cells may be relevant, in mucosal tissues, in supporting or integrating the scavenging activity of resident macrophages. PMID:11452003

  16. Localised proton magnetic resonance spectroscopy of the brain after perinatal hypoxia: a preliminary report

    Energy Technology Data Exchange (ETDEWEB)

    Chateil, J.F. [Service de Radiologie A, Hopital Pellegrin, Bordeaux (France)]|[Unite de Radiopediatrie, Hopital Pellegrin, Bordeaux (France); Quesson, B.; Thiaudiere, E.; Delalande, C.; Canioni, P. [Resonance Magnetique des Systemes Biologiques, CNRS, Bordeaux (France); Brun, M.; Diard, F. [Service de Radiologie A, Hopital Pellegrin, Bordeaux (France); Sarlangue, J.; Billeaud, C. [Service de Neonatalogie, Hopital Pellegrin, Bordeaux (France)

    1999-03-01

    Objectives. Perinatal hypoxic ischaemic injury is a significant cause of neurodevelopmental impairment. The aim of this study was to evaluate localised proton magnetic resonance spectroscopy ({sup 1}H-MRS) after birth asphyxia. Materials and methods. Thirty newborn infants suspected of having perinatal asphyxia (Apgar score < 3) were studied. The mean gestational age was 37 weeks, mean age at the MR examination was 18 days and mean weight was 2.9 kg. A 1.5-T unit was used for imaging and spectroscopy. None of the babies had mechanically assisted ventilation. No sedation was used. Axial T1-weighted and T2-weighted images were obtained. {sup 1}H-MRS was recorded in a single voxel, localised in white matter, using a STEAM sequence. Results. Image quality was good in 25 of 30 babies. {sup 1}H-MRS was performed in 19 of 30 subjects, with adequate quality in 16. Choline, creatine/phosphocreatine and N-acetylaspartate peaks and peak-area ratios were analysed. Lactate was detected in four infants. The N-acetylaspartate/choline ratio was lower in infants with an impaired neurological outcome, but the difference was not statistically significant. Conclusions. This study suggests that {sup 1}H-MRS may be useful for assessing cerebral metabolism in the neonate. A raised lactate level and decreased N-acetylaspartate/choline ratio may be predictive of a poor outcome. However, in our experience this method is limited by the difficulty in performing the examination during the first hours after birth in critically ill babies, the problems related to use of a monovoxel sequence, the dispersion of the ratios and the lack of determination of the absolute concentration of the metabolites. (orig.) With 3 figs., 2 tabs., 20 refs.

  17. Localisation of a channel instability in a BWR via neutron noise methods

    International Nuclear Information System (INIS)

    Karlsson, J.K.H.; Pazsit, I.

    1998-01-01

    A special type of instability occurred in the Swedish BWR Forsmark 1 in 1996. In contrast to the better known global or regional (out-of-phase) instabilities, the decay ratio appeared to be very high in one half of the core and quite low in the other half. A more detailed analysis showed that the most likely reason for the observed behaviour is a local perturbation of thermohydraulic character, e.g. a density wave oscillation (DWO), induced by the incorrect positioning of a fuel assembly (an 'unseated' assembly). In such a case it is of large importance to determine the position of the unseated assembly already during operation such that it can be easily found during reloading. The subject of this paper is to report on development and application of methods by which the position of such a local perturbation can be determined. Two different methods that support and complement each other were used. First a visualisation technique was elaborated which expedites a very good qualitative comprehension of the situation and which can be useful for the operators. It also gives an important basis for the application of the localisation algorithm. Second, a quantitative (algorithmic) localisation method, suited for this type of perturbation, was elaborated. This latter takes noise spectra from selected detectors as input and yields the perturbation position as output. The method was tested on simulated data, and then applied to the Forsmark measurements. The location of the disturbance, found by the algorithm, is in accordance with independent judgements for the case, and close to a position where an unseated assembly was found during refuelling. (author)

  18. An approach for evaluating the general and localised corrosion of carbon steel containers for nuclear waste disposal

    International Nuclear Information System (INIS)

    Marsh, G.P.; Taylor, K.J.; Sharland, S.M.; Tasker, P.W.

    1987-06-01

    The paper considers the long term corrosion of carbon steel containers for heat generating nuclear waste in a granitic repository. Under such conditions carbon steel may exhibit general, localised or passive corrosion behaviour depending on the exact composition and redox potential of the groundwater contacting the containers; localised corrosion being of most concern because it has the fastest propagation rate. It is well established, however, that such localised corrosion is only possible when the environment is sufficiently oxidising to maintain a positive potential gradient between the cathodic surface and the corrosion sites, which requires that species which oxidising potentials greater than water need to be present. This fact provides a basis for estimating the periods during which containers may be subject to localised and subsequently to general corrosion, and hence for making an overall assessment of the metal allowance required for a specified container life. A model for the diffusion transport of oxygen has been developed, and a sensitivity analysis has shown that the period of possible attack is strongly dependent on the passive film leakage current, the radiation dose rate and the oxygen diffusion coefficient. (orig.)

  19. Evaluation of different types of sensors and their positioning for on-line PD detection and localisation in distribution cables

    NARCIS (Netherlands)

    Wielen, van der P.C.J.M.; Veen, J.; Wouters, P.A.A.F.

    2003-01-01

    Different types of sensors can be used for on-line detection and localisation of PDs in medium voltage cables. These sensors can be placed on different locations in the substa-tions where the cable under test is terminated. Both aspects have a significant influence on the measured signals. In this

  20. Momentum and scalar transport in a localised synthetic turbulence in a channel flow with a short contraction

    Energy Technology Data Exchange (ETDEWEB)

    Lefeuvre, N; Djenidi, L [University of Newcastle, NSW Australia (Australia); Tardu, S, E-mail: nathan.lefeuvre@uon.edu.au [Laboratoire des Ecoulements Geophysiques et Industriels (LEGI), Grenoble (France)

    2011-12-22

    A numerical simulation is undertaken to investigate the transport of momentum and a passive scalar in a localised turbulence in a channel with a contraction. The simulation is carried out using a hybrid method which combines the lattice Boltzmann method (LBM, for the velocity field) and the energy equation (for the temperature field). The localised turbulence is generated through pulsed jets issued in the Poiseuille flow developing in the channel at a Reynolds number of about 1000. The aim of the study is twofold : i) determine effect of the contraction on the localised turbulence, and ii) study how the passive scalar behaves in such contracted localised turbulence. The contraction increase the averaged vorticity in the channel flow, which is accompanied by an increase in the averaged kinetic energy. The contraction also tends to reduce the Reynolds stresses. These results are similar those obtained in turbulent pipe flow with an axisymmetric contraction and in a turbulent boundary layer subjected to a favourable pressure gradient. However, it is found that the heat transport in the normal to the wall direction is more dramatically affected (reduced) than that in the direction of the flow.

  1. Challenges to Globalisation, Localisation and Sinophilia in Music Education: A Comparative Study of Hong Kong, Shanghai and Taipei

    Science.gov (United States)

    Ho, Wai-Chung; Law, Wing-Wah

    2006-01-01

    In the past, the music curricula of Hong Kong (HK), Mainland China and Taiwan have focused on Western music, but with the advent of music technology and the new tripartite paradigm of globalisation, localisation and Sinophilia this has begun to change. Hong Kong, Shanghai and Taipei share a common historical culture and their populations are…

  2. Basolateral localisation of KCNQ1 potassium channels in MDCK cells: molecular identification of an N-terminal targeting motif

    DEFF Research Database (Denmark)

    Jespersen, Thomas; Rasmussen, Hanne B; Grunnet, Morten

    2004-01-01

    of the tyrosine residue at position 51 resulted in a non-polarized steady-state distribution of the channel. The importance of tyrosine 51 in basolateral localisation was emphasized by the fact that a short peptide comprising this tyrosine was able to redirect the p75 neurotrophin receptor, an otherwise apically...

  3. Usefulness and limits of ultrasound guided hook-wire positioning for localisation of soft tissue lesions prior to surgery

    International Nuclear Information System (INIS)

    Trenaghi, Alberto; Dal Bosco, Chiara; Talenti, Enrico; Rubaltelli, Enrico; Borsato, Simonetta; Rossi, Carlo Riccardo; Lumachi, Franco

    2005-01-01

    Purpose. The aim of our study was to assess the usefulness of positioning metal wires under ultrasound guidance for localising soft tissue lesions in the preoperative phase. Materials and methods. We studied superficial soft-tissue lesions in 12 patients, using hooked mammographic wires of different lengths. One patient had a multifocal growth of disease which required a double localisation procedure. Correct positioning of the wire was confirmed by ultrasonography. All patients underwent surgery within five hours of hook-wire positioning. Results. Correct wire position was confirmed at surgery in 12 out of 13 procedures. In one case the hook-wire reached the margin of the lesion. In all cases, the preoperative localisation procedure facilitated identification and resection of the masses. Conclusions. In our experience, the main indications for hook-wire positioning before surgery are: marking of small lesions, localisation of lesions in anatomic areas structurally subverted by previous surgery and consequently difficult to detect, guidance for surgical sectioning in order to safeguard the noble structures dose to the lesions [it

  4. Localising QTLs for leaf rust resistance and agronomic traits in barley (¤Hordeum vulgare¤ L.)

    DEFF Research Database (Denmark)

    Kicherer, S.; Backes, G.; Walther, U.

    2000-01-01

    to leaf rust by means of artificial infection, heading date, plant height and Kernel weight were assessed. For leaf rust resistance, 4 QTLs were localised, that explained 96.1% of the genetic variation. One QTL on chromosome 4H confirmed a position found in another genetic background and one mapped...

  5. Treatment of localised resectable neuroblastoma. Results of the LNESG1 study by the SIOP Europe Neuroblastoma Group

    NARCIS (Netherlands)

    de Bernardi, B.; Mosseri, V.; Rubie, H.; Castel, V.; Foot, A.; Ladenstein, R.; Laureys, G.; Beck-Popovic, M.; de Lacerda, A. F.; Pearson, A. D. J.; de Kraker, J.; Ambros, P. F.; de Rycke, Y.; Conte, M.; Bruzzi, P.; Michon, J.

    2008-01-01

    Main objective of this study was to confirm that surgery alone is an effective and safe treatment for localised resectable neuroblastoma except stage 2 with amplified MYCN gene (MYCNA). Of 427 eligible stages 1-2 patients, 411 had normal MYCN and 16 had MYCNA. Of the 288 stage 1 patients with normal

  6. Contralateral routing of signals disrupts monaural level and spectral cues to sound localisation on the horizontal plane.

    Science.gov (United States)

    Pedley, Adam J; Kitterick, Pádraig T

    2017-09-01

    Contra-lateral routing of signals (CROS) devices re-route sound between the deaf and hearing ears of unilaterally-deaf individuals. This rerouting would be expected to disrupt access to monaural level cues that can support monaural localisation in the horizontal plane. However, such a detrimental effect has not been confirmed by clinical studies of CROS use. The present study aimed to exercise strict experimental control over the availability of monaural cues to localisation in the horizontal plane and the fitting of the CROS device to assess whether signal routing can impair the ability to locate sources of sound and, if so, whether CROS selectively disrupts monaural level or spectral cues to horizontal location, or both. Unilateral deafness and CROS device use were simulated in twelve normal hearing participants. Monaural recordings of broadband white noise presented from three spatial locations (-60°, 0°, and +60°) were made in the ear canal of a model listener using a probe microphone with and without a CROS device. The recordings were presented to participants via an insert earphone placed in their right ear. The recordings were processed to disrupt either monaural level or spectral cues to horizontal sound location by roving presentation level or the energy across adjacent frequency bands, respectively. Localisation ability was assessed using a three-alternative forced-choice spatial discrimination task. Participants localised above chance levels in all conditions. Spatial discrimination accuracy was poorer when participants only had access to monaural spectral cues compared to when monaural level cues were available. CROS use impaired localisation significantly regardless of whether level or spectral cues were available. For both cues, signal re-routing had a detrimental effect on the ability to localise sounds originating from the side of the deaf ear (-60°). CROS use also impaired the ability to use level cues to localise sounds originating from

  7. Influence of the radio-tracer used in diagnostic nuclear medicine upon the dose at the nucleus of cellular localisation

    International Nuclear Information System (INIS)

    Gardin, I.; Faraggi, M.; Stievenart, J.L; Le Guludec, D.; Bok, B.

    1997-01-01

    In the classical dosimetry one supposes a uniform distribution of the radio-pharmaceuticals at the source organ level as well as a homogeneous distribution of the absorbed dose. This hypotheses are not always verified in biology, and the influence of the tracer localisation on the dose delivered at the cellular nucleus has been studied. The average dose delivered by the electron emission of different radio-isotopes used in diagnosis has been calculated by taking into account the radioactivity localized upon the target cell (Dself), and upon the neighbouring cells (Dcross). Nuclear, cytoplasmic and membranous localizations of the tracer were simulated for different cellular sizes. In the particular case of 99m Tc and cells of nuclear radius about 4 μm and cellular radios about 8 μ, Dcross is independent of the intra-cellular localisation of the tracer. On the contrary, for a nuclear localisation Dself is 52 and 157 times more important than for the cytoplasmic and membranous localisation, respectively. The dose at the cellular nucleus due to electron emission of 99m Tc is under-estimated by a factor 2.6 by classical dosimetry when the radioactivity is nuclear. On the contrary, the classical model over-estimates by a factor 1.2 the dose at nucleus for cytoplasmic and membranous localizations. This study shows that the dose delivered at cellular nucleus by the electron emissions of 99m Tc depends on the localisation of the tracer. The modelling proposed allows a better evaluation of the radiobiological hazards related to the administration of radiopharmaceuticals in diagnostic nuclear medicine

  8. Involvement of Chromatin Remodeling Genes and the Rho GTPases RhoB and CDC42 in Ovarian Clear Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Nicolai Skovbjerg Arildsen

    2017-05-01

    Full Text Available ObjectiveOvarian clear cell carcinomas (OCCCs constitute a rare ovarian cancer subtype with distinct clinical features, but may nonetheless be difficult to distinguish morphologically from other subtypes. There is limited knowledge of genetic events driving OCCC tumorigenesis beyond ARID1A, which is reportedly mutated in 30–50% of OCCCs. We aimed to further characterize OCCCs by combined global transcriptional profiling and targeted deep sequencing of a panel of well-established cancer genes. Increased knowledge of OCCC-specific genetic aberrations may help in guiding development of targeted treatments and ultimately improve patient outcome.MethodsGene expression profiling of formalin-fixed, paraffin-embedded (FFPE tissue from a cohort of the major ovarian cancer subtypes (cohort 1; n = 67 was performed using whole-genome cDNA-mediated Annealing, Selection, extension and Ligation (WG-DASL bead arrays, followed by pathway, gene module score, and gene ontology analyses, respectively. A second FFPE cohort of 10 primary OCCCs was analyzed by targeted DNA sequencing of a panel of 60 cancer-related genes (cohort 2. Non-synonymous and non-sense variants affecting single-nucleotide variations and insertions or deletions were further analyzed. A tissue microarray of 43 OCCCs (cohort 3 was used for validation by immunohistochemistry and chromogenic in situ hybridization.ResultsGene expression analyses revealed a distinct OCCC profile compared to other histological subtypes, with, e.g., ERBB2, TFAP2A, and genes related to cytoskeletal actin regulation being overexpressed in OCCC. ERBB2 was, however, not overexpressed on the protein level and ERBB2 amplification was rare in the validation cohort. Targeted deep sequencing revealed non-synonymous variants or insertions/deletions in 11/60 cancer-related genes. Genes involved in chromatin remodeling, including ARID1A, SPOP, and KMT2D were frequently mutated across OCCC tumors.ConclusionOCCCs appear genetically heterogeneous, but harbor frequent alterations in chromatin remodeling genes. Overexpression of TFAP2A and ERBB2 was observed on the mRNA level in relation to other ovarian cancer subtypes. However, overexpression of ERBB2 was not reflected by HER2 amplification or protein overexpression in the OCCC validation cohort. In addition, Rho GTPase-dependent actin organization may also play a role in OCCC pathogenesis and warrants further investigation. The distinct biological features of OCCC discovered here may provide a basis for novel targeted treatment strategies.

  9. Spatial Determinants on Export marketing activity in Marshallian Districts: An investigation of the Danish Furniture Industry

    DEFF Research Database (Denmark)

    Andersen, Poul Houman

    2002-01-01

    The purpose of the contribution is investigate the role of localised districts on the organisation of export activities in small and medium-sized furniture producers. To what extent do local environments influence the export activities taken on by firms?......The purpose of the contribution is investigate the role of localised districts on the organisation of export activities in small and medium-sized furniture producers. To what extent do local environments influence the export activities taken on by firms?...

  10. Mineral Replacement Reactions as a Precursor to Strain Localisation: an (HR-)EBSD approach

    Science.gov (United States)

    Gardner, J.; Wheeler, J.; Wallis, D.; Hansen, L. N.; Mariani, E.

    2017-12-01

    Much remains to be learned about the links between metamorphism and deformation. Our work investigates the behaviour of fluid-mediated mineral replacement reaction products when exposed to subsequent shear stresses. We focus on albite from a metagabbro that has experienced metamorphism and subsequent deformation at greenschist facies, resulting in a reduction in grain size and associated strain localisation. EBSD maps show that prior to grain size reduction, product grains are highly distorted, yet they formed, and subsequently deformed, at temperatures at which extensive dislocation creep is unlikely. The Weighted Burgers Vector can be used to quantitatively describe the types of Burgers vectors present in geometrically necessary dislocation (GND) populations derived from 2-D EBSD map data. Application of this technique to the distorted product grains reveals the prominence of, among others, dislocations with apparent [010] Burgers vectors. This supports (with some caveats) the idea that dislocation creep is not responsible for the observed lattice distortion, as there are no known slip systems in plagioclase with a [010] Burgers vector. Distortion in a replacement microstructure has also been attributed to the presence of nanoscale product grains, which share very similar, but not identical, orientations due to topotactic nucleation from adjacent sites on the same substrate. As a precipitate, the product grains should be expected to be largely free of elastic strain. However, high angular resolution EBSD results demonstrate that product grains contain both elastic strains (> 10-3) and residual stresses (several hundred MPa), as well as GND densities on the order of 1014-1015 m-2. Thus we suggest the observed distortion (elastic strain plus rotations) in the lattice is produced during the mineral replacement reaction by a lattice mismatch and volume change between parent and product. Stored strain energy then provides a driving force for recovery and

  11. The effects of localised fatigue on upper extremity jump shot kinematics and kinetics in team handball.

    Science.gov (United States)

    Plummer, Hillary A; Oliver, Gretchen D

    2017-01-01

    Team handball is a popular sport worldwide that requires numerous throws to be made throughout the course of a game. Because of the upper extremity demands of repetitive throwing, it is possible that fatigue can alter the mechanics of a shot. The purpose of this study was to determine the influence of localised fatigue on jump shot kinematics and kinetics. Eleven male team handball players (23.1 ± 3.1 years; 185.1 ± 8.3 cm; 89.7 ± 12.2 kg) volunteered. An electromagnetic tracking system was used to examine the jump shot prior to and following localised fatigue. The fatiguing protocol consisted of throwing a 2.2 kg medicine ball into a rebounder until volitional fatigue. No significant kinematic or kinetic differences were observed following fatigue. Shoulder external rotation was -74.8 ± 14.9° prior to and -79.0 ± 14.7° following fatigue at MER. Scapula, external rotation at ball release (BR) prior to fatigue was -2.2 ± 7.0° and -3.2 ± 11.1° following fatigue. Scapular internal rotation, at maximum shoulder internal rotation (MIR), changed from 18.4 ± 11.2° to 20.4 ± 11.8°. Ball velocity decreased from19.8 m · s -1 to 18.8 m · s -1 (P = 0.12). Accuracy percentage in the pre-fatigue trials was 60.8 ± 14.1% and 52.8 ± 12.7% following fatigue (P = 0.20). While no significant changes were observed, it is possible that other fatiguing protocols that more closely represent the aerobic and throwing demands of the sport may have a greater effect on the kinematics and kinetics of the jump shot.

  12. Magneto-hydro-dynamic simulation of Edge-Localised-Modes in tokamaks

    International Nuclear Information System (INIS)

    Pamela, S.

    2010-01-01

    In order to produce energy from fusion reactions in a tokamak, the plasma must reach temperatures higher than that of our sun. The operation regime called H-mode enables one to acquire a plasma confinement close to fusion conditions. Due to the formation of a transport barrier at the plasma edge, turbulent transport is reduced, and the total plasma pressure increases, resulting in a strong pressure gradient at the edge. If this pressure gradient, localised at the plasma-vacuum boundary, becomes too steep, a magneto-hydro-dynamic instability is triggered and part of the plasma pressure is lost. This instability, hence called Edge-Localised-Mode, provokes large heat fluxes on some of the plasma-facing components of the machine, which could set operational limits for a tokamak the size of ITER. In order to understand this instability, and to determine the non-linear mechanisms behind the ELMs, the JOREK code is used. The work presented in this thesis is based on MHD simulations of ballooning modes (responsible for ELMs) with the JOREK code. At first, simulations are done for standard plasmas, inspired of experimental machines. In particular, the plasma rotation at equilibrium, in the region of the edge pressure gradient, is studied in order to obtain an analysis of the effects that such a rotation can have on the linear stability of ELMs and on their non-linear evolution. Then, as a second step, simulations are applied to plasmas of the experimental tokamaks JET and MAST (England). This permits the direct comparison of simulation results with experimental observations, with the main goal of improving our global understanding of ELMs. Adding to this physics aspect, the confrontation of the JOREK code with diagnostics of JET and MAST brings to a validation of simulations, which should prove that the simulations which were obtained do correspond to ELM instabilities. This first step towards the validation of the code is crucial concerning the simulation of ELMs in ITER

  13. Synapses of Amphids Defective (SAD-A) Kinase Promotes Glucose-stimulated Insulin Secretion through Activation of p21-activated Kinase (PAK1) in Pancreatic β-Cells*

    Science.gov (United States)

    Nie, Jia; Sun, Chao; Faruque, Omar; Ye, Guangming; Li, Jia; Liang, Qiangrong; Chang, Zhijie; Yang, Wannian; Han, Xiao; Shi, Yuguang

    2012-01-01

    The p21-activated kinase-1 (PAK1) is implicated in regulation of insulin exocytosis as an effector of Rho GTPases. PAK1 is activated by the onset of glucose-stimulated insulin secretion (GSIS) through phosphorylation of Thr-423, a major activation site by Cdc42 and Rac1. However, the kinase(s) that phosphorylates PAK1 at Thr-423 in islet β-cells remains elusive. The present studies identified SAD-A (synapses of amphids defective), a member of AMP-activated protein kinase-related kinases exclusively expressed in brain and pancreas, as a key regulator of GSIS through activation of PAK1. We show that SAD-A directly binds to PAK1 through its kinase domain. The interaction is mediated by the p21-binding domain (PBD) of PAK1 and requires both kinases in an active conformation. The binding leads to direct phosphorylation of PAK1 at Thr-423 by SAD-A, triggering the onset of GSIS from islet β-cells. Consequently, ablation of PAK1 kinase activity or depletion of PAK1 expression completely abolishes the potentiating effect of SAD-A on GSIS. Consistent with its role in regulating GSIS, overexpression of SAD-A in MIN6 islet β-cells significantly stimulated cytoskeletal remodeling, which is required for insulin exocytosis. Together, the present studies identified a critical role of SAD-A in the activation of PAK1 during the onset of insulin exocytosis. PMID:22669945

  14. Synapses of amphids defective (SAD-A) kinase promotes glucose-stimulated insulin secretion through activation of p21-activated kinase (PAK1) in pancreatic β-Cells.

    Science.gov (United States)

    Nie, Jia; Sun, Chao; Faruque, Omar; Ye, Guangming; Li, Jia; Liang, Qiangrong; Chang, Zhijie; Yang, Wannian; Han, Xiao; Shi, Yuguang

    2012-07-27

    The p21-activated kinase-1 (PAK1) is implicated in regulation of insulin exocytosis as an effector of Rho GTPases. PAK1 is activated by the onset of glucose-stimulated insulin secretion (GSIS) through phosphorylation of Thr-423, a major activation site by Cdc42 and Rac1. However, the kinase(s) that phosphorylates PAK1 at Thr-423 in islet β-cells remains elusive. The present studies identified SAD-A (synapses of amphids defective), a member of AMP-activated protein kinase-related kinases exclusively expressed in brain and pancreas, as a key regulator of GSIS through activation of PAK1. We show that SAD-A directly binds to PAK1 through its kinase domain. The interaction is mediated by the p21-binding domain (PBD) of PAK1 and requires both kinases in an active conformation. The binding leads to direct phosphorylation of PAK1 at Thr-423 by SAD-A, triggering the onset of GSIS from islet β-cells. Consequently, ablation of PAK1 kinase activity or depletion of PAK1 expression completely abolishes the potentiating effect of SAD-A on GSIS. Consistent with its role in regulating GSIS, overexpression of SAD-A in MIN6 islet β-cells significantly stimulated cytoskeletal remodeling, which is required for insulin exocytosis. Together, the present studies identified a critical role of SAD-A in the activation of PAK1 during the onset of insulin exocytosis.

  15. Radiographer-led breast boost localisation – A service evaluation study

    International Nuclear Information System (INIS)

    Smith, S.; Comins, C.

    2015-01-01

    A radiation boost to the tumour bed as part of breast conserving therapy reduces the rate of local recurrence. Radiographer-led planning for tangential field radiotherapy has been the practice at our centre since 2007. The transition from conventional simulation to computed tomography (CT) and virtual simulation enhanced the radiographer's role in the breast planning process. Electron boost mark ups continued to be marked up freehand by doctors using available imaging to determine tumour bed. The paper reports on a service evaluation undertaken to establish a change in practice for electron breast boosts to be simulated using the virtual simulator by suitably trained radiographers. The retrospective simulation of ten patients confirmed the consistency of radiographer tumour bed localisation, followed by the prospective simulation of ten patients' boost fields. The introduction of a radiographer-led planning breast boost service has given greater autonomy and job satisfaction to individuals as well as resulting in a cost effective use of available resources. - Highlights: • A service evaluation study was undertaken to train a radiographer to perform breast boost planning. • Retrospective breast boost planning established proposed technique was workable. • Prospective planning by radiographer proved their competence. • Introduction of new technique provided job satisfaction and service improvement

  16. Targetted localisation and imaging of a murine lymphoma using 131I-labelled monoclonal antibody

    International Nuclear Information System (INIS)

    Subbiah, Krishnan; Rayala, Suresh Kumar; Ananthanarayanan, Meenakshi; Thangarajan, Rajkumar

    2001-01-01

    In vivo tumor targetting with radiolabelled monoclonal antibodies is a promising approach for the diagnosis and therapy of tumors. A specific monoclonal antibody (mAb), DLAB was generated to the Dalton's lymphoma associated antigen (DLAA) from Haemophilus paragallinarum -induced spontaneous fusion. In order to study the tumor localisation and biodistribution properties of the monoclonal antibody, scintigraphic studies were performed using the radiolabelled DLAB. 131I -labelled DLAB was administered intravenously into Swiss mice bearing Dalton's lymphoma and external scintiscanning was performed at different time intervals. Clear tumor images were obtained which revealed selective and specific uptake of radiolabel and the results were compared with biodistribution data. The radioiodinated monoclonal antibody showed fast tumor uptake which increased significantly to 14.6% injected dose (ID)/g at 12 hr post-injection. Enhanced blood clearance of radioactivity resulted in higher tumor/blood ratio of 5.96 at 48 hr. 131I -labelled DLAB resulted in selective and enhanced uptake of the radioactivity by the tumor compared to the non-specific antibody and the results suggest the potential use of spontaneous fusion for producing specific monoclonal antibodies for tumor detection and therapy. (author)

  17. Real time determination and control of the plasma localisation and internal inductance in Tore Supra

    Energy Technology Data Exchange (ETDEWEB)

    Saint-Laurent, F. E-mail: stlauren@drfc.cad.cea.fr; Martin, G

    2001-10-01

    The study of long-duration high-power discharges need an efficient real time control of the plasma parameters, especially the plasma position when RF heating systems are used. On Tore Supra, recent improvements have been carried out (i) for the poloidal interpolation and the radial extrapolation of the magnetic measurements, (ii) for a better feedback matrix converting the radial errors of the plasma position to voltage values for the poloidal generators, and (iii) for a very fast solution to find the plasma parameters from the knowledge of its surface. The plasma edge localisation is now controlled with a precision better than 1 cm and controlled within a few millimetres uncertainty for several tenths of seconds. Moreover, for advanced tokamak scenarios, a precise real time determination of safety factor, poloidal beta, internal inductance, Shafranov shift as well as the online computation of the electron density and current density profiles are now available on Tore Supra. These quantities compare well with results from batch calculations using an equilibrium code. To fulfil the new requirements of plasma control for the CIEL project, a local control of the plasma edge position and curvature is planned for the near future.

  18. The terminal region of the E. coli chromosome localises at the periphery of the nucleoid

    Directory of Open Access Journals (Sweden)

    Stouf Mathieu

    2011-02-01

    Full Text Available Abstract Background Bacterial chromosomes are organised into a compact and dynamic structures termed nucleoids. Cytological studies in model rod-shaped bacteria show that the different regions of the chromosome display distinct and specific sub-cellular positioning and choreographies during the course of the cell cycle. The localisation of chromosome loci along the length of the cell has been described. However, positioning of loci across the width of the cell has not been determined. Results Here, we show that it is possible to assess the mean positioning of chromosomal loci across the width of the cell using two-dimension images from wide-field fluorescence microscopy. Observed apparent distributions of fluorescent-tagged loci of the E. coli chromosome along the cell diameter were compared with simulated distributions calculated using a range of cell width positioning models. Using this method, we detected the migration of chromosome loci towards the cell periphery induced by production of the bacteriophage T4 Ndd protein. In the absence of Ndd production, loci outside the replication terminus were located either randomly along the nucleoid width or towards the cell centre whereas loci inside the replication terminus were located at the periphery of the nucleoid in contrast to other loci. Conclusions Our approach allows to reliably observing the positioning of chromosome loci along the width of E. coli cells. The terminal region of the chromosome is preferentially located at the periphery of the nucleoid consistent with its specific roles in chromosome organisation and dynamics.

  19. Dynamic localisation of mature microRNAs in Human nucleoli is influenced by exogenous genetic materials.

    Science.gov (United States)

    Li, Zhou Fang; Liang, Yi Min; Lau, Pui Ngan; Shen, Wei; Wang, Dai Kui; Cheung, Wing Tai; Xue, Chun Jason; Poon, Lit Man; Lam, Yun Wah

    2013-01-01

    Although microRNAs are commonly known to function as a component of RNA-induced silencing complexes in the cytoplasm, they have been detected in other organelles, notably the nucleus and the nucleolus, of mammalian cells. We have conducted a systematic search for miRNAs in HeLa cell nucleoli, and identified 11 abundant miRNAs with a high level of nucleolar accumulation. Through in situ hybridisation, we have localised these miRNAs, including miR-191 and miR-484, in the nucleolus of a diversity of human and rodent cell lines. The nucleolar association of these miRNAs is resistant to various cellular stresses, but highly sensitive to the presence of exogenous nucleic acids. Introduction of both single- and double-stranded DNA as well as double stranded RNA rapidly induce the redistribution of nucleolar miRNAs to the cytoplasm. A similar change in subcellular distribution is also observed in cells infected with the influenza A virus. The partition of miRNAs between the nucleolus and the cytoplasm is affected by Leptomycin B, suggesting a role of Exportin-1 in the intracellular shuttling of miRNAs. This study reveals a previously unknown aspect of miRNA biology, and suggests a possible link between these small noncoding RNAs and the cellular management of foreign genetic materials.

  20. Analysis of mitochondrial function and localisation during human embryonic stem cell differentiation in vitro.

    Directory of Open Access Journals (Sweden)

    Andrew B J Prowse

    Full Text Available Human embryonic stem cell (hESC derivatives show promise as viable cell therapy options for multiple disorders in different tissues. Recent advances in stem cell biology have lead to the reliable production and detailed molecular characterisation of a range of cell-types. However, the role of mitochondria during differentiation has yet to be fully elucidated. Mitochondria mediate a cells response to altered energy requirements (e.g. cardiomyocyte contraction and, as such, the mitochondrial phenotype is likely to change during the dynamic process of hESC differentiation. We demonstrate that manipulating mitochondrial biogenesis alters mesendoderm commitment. To investigate mitochondrial localisation during early lineage specification of hESCs we developed a mitochondrial reporter line, KMEL2, in which sequences encoding the green fluorescent protein (GFP are targeted to the mitochondria. Differentiation of KMEL2 lines into the three germ layers showed that the mitochondria in these differentiated progeny are GFP positive. Therefore, KMEL2 hESCs facilitate the study of mitochondria in a range of cell types and, importantly, permit real-time analysis of mitochondria via the GFP tag.

  1. Dynamic localisation of mature microRNAs in Human nucleoli is influenced by exogenous genetic materials.

    Directory of Open Access Journals (Sweden)

    Zhou Fang Li

    Full Text Available Although microRNAs are commonly known to function as a component of RNA-induced silencing complexes in the cytoplasm, they have been detected in other organelles, notably the nucleus and the nucleolus, of mammalian cells. We have conducted a systematic search for miRNAs in HeLa cell nucleoli, and identified 11 abundant miRNAs with a high level of nucleolar accumulation. Through in situ hybridisation, we have localised these miRNAs, including miR-191 and miR-484, in the nucleolus of a diversity of human and rodent cell lines. The nucleolar association of these miRNAs is resistant to various cellular stresses, but highly sensitive to the presence of exogenous nucleic acids. Introduction of both single- and double-stranded DNA as well as double stranded RNA rapidly induce the redistribution of nucleolar miRNAs to the cytoplasm. A similar change in subcellular distribution is also observed in cells infected with the influenza A virus. The partition of miRNAs between the nucleolus and the cytoplasm is affected by Leptomycin B, suggesting a role of Exportin-1 in the intracellular shuttling of miRNAs. This study reveals a previously unknown aspect of miRNA biology, and suggests a possible link between these small noncoding RNAs and the cellular management of foreign genetic materials.

  2. Localisation of the brain in fetal MRI using bundled SIFT features.

    Science.gov (United States)

    Keraudren, Kevin; Kyriakopoulou, Vanessa; Rutherford, Mary; Hajnal, Joseph V; Rueckert, Daniel

    2013-01-01

    Fetal MRI is a rapidly emerging diagnostic imaging tool. Its main focus is currently on brain imaging, but there is a huge potential for whole body studies. We propose a method for accurate and robust localisation of the fetal brain in MRI when the image data is acquired as a stack of 2D slices misaligned due to fetal motion. We first detect possible brain locations in 2D images with a Bag-of-Words model using SIFT features aggregated within Maximally Stable Extremal Regions (called bundled SIFT), followed by a robust fitting of an axis-aligned 3D box to the selected regions. We rely on prior knowledge of the fetal brain development to define size and shape constraints. In a cross-validation experiment, we obtained a median error distance of 5.7mm from the ground truth and no missed detection on a database of 59 fetuses. This 2D approach thus allows a robust detection even in the presence of substantial fetal motion.

  3. On the localisation of four-dimensional brane-world black holes: II. The general case

    International Nuclear Information System (INIS)

    Kanti, P; Pappas, T; Pappas, N

    2016-01-01

    We perform a comprehensive analysis of a number of scalar field theories in an attempt to find analytically five-dimensional, localised-on-the-brane, black-hole solutions. Extending a previous analysis, we assume a generalised Vaidya ansatz for the five-dimensional metric tensor that allows for a time-dependent, non-trivial profile of the mass function in terms of the bulk coordinate and a deviation from the over-restricting Schwarzschild-type solution on the brane. In order to support such a solution, we study a variety of theories including single or multiple scalar fields, with canonical or non-canonical kinetic terms, minimally or non-minimally coupled to gravity. We demonstrate that for such a metric ansatz and for a carefully chosen energy-momentum tensor which is non-isotropic in five dimensions, solutions that have the form of a Schwarzschild–(anti)de Sitter or Reissner–Nordstrom type of solution do emerge. However, the resulting profile of the mass function along the bulk coordinate, when allowed, is not the correct one for eliminating bulk singularities. (paper)

  4. On the localisation of four-dimensional brane-world black holes: II. The general case

    Science.gov (United States)

    Kanti, P.; Pappas, N.; Pappas, T.

    2016-01-01

    We perform a comprehensive analysis of a number of scalar field theories in an attempt to find analytically five-dimensional, localised-on-the-brane, black-hole solutions. Extending a previous analysis, we assume a generalised Vaidya ansatz for the five-dimensional metric tensor that allows for a time-dependent, non-trivial profile of the mass function in terms of the bulk coordinate and a deviation from the over-restricting Schwarzschild-type solution on the brane. In order to support such a solution, we study a variety of theories including single or multiple scalar fields, with canonical or non-canonical kinetic terms, minimally or non-minimally coupled to gravity. We demonstrate that for such a metric ansatz and for a carefully chosen energy-momentum tensor which is non-isotropic in five dimensions, solutions that have the form of a Schwarzschild-(anti)de Sitter or Reissner-Nordstrom type of solution do emerge. However, the resulting profile of the mass function along the bulk coordinate, when allowed, is not the correct one for eliminating bulk singularities.

  5. Pressure-induced localisation of the hydrogen-bond network in KOH-VI

    Energy Technology Data Exchange (ETDEWEB)

    Hermann, Andreas, E-mail: a.hermann@ed.ac.uk; Nelmes, Richard J.; Loveday, John S. [Centre for Science at Extreme Conditions and SUPA, School of Physics and Astronomy, The University of Edinburgh, Edinburgh EH9 3JZ (United Kingdom); Guthrie, Malcolm [Centre for Science at Extreme Conditions and SUPA, School of Physics and Astronomy, The University of Edinburgh, Edinburgh EH9 3JZ (United Kingdom); European Spallation Source AB, P.O. Box 176, SE-22100 Lund (Sweden)

    2015-12-28

    Using a combination of ab initio crystal structure prediction and neutron diffraction techniques, we have solved the full structure of KOH-VI at 7 GPa. Rather than being orthorhombic and proton-ordered as had previously be proposed, we find that this high-pressure phase of potassium hydroxide is tetragonal (space group I4/mmm) and proton disordered. It has an unusual hydrogen bond topology, where the hydroxyl groups form isolated hydrogen-bonded square planar (OH){sub 4} units. This structure is stable above 6.5 GPa and, despite being macroscopically proton-disordered, local ice rules enforce microscopic order of the hydrogen bonds. We suggest the use of this novel type of structure to study concerted proton tunneling in the solid state, while the topology of the hydrogen bond network could conceivably be exploited in data storage applications based solely on the manipulations of hydrogen bonds. The unusual localisation of the hydrogen bond network under applied pressure is found to be favored by a more compact packing of the constituents in a distorted cesium chloride structure.

  6. Gas in the rectum tends to reduce during radical external beam radiotherapy for localised prostate cancer

    International Nuclear Information System (INIS)

    Nakamura, Naoki; Mizuno, Norifumo; Endo, Haruna; Ogita, Mami; Kawamori, Jiro; Sekigucho, Kenji; Hatanaka, Shogo; Takahashi, Osamu; Tamaki, Seiichi; Shikama, Naoto

    2014-01-01

    This study aims to clarify the time-course of gas accumulation in the rectum during treatment as guidance for the management of rectal volumes. We reviewed 2042 sets (35.2 sets per patient) of anteroposterior and right–left mega voltage (MV) images obtained for daily set-up from 58 patients who underwent radical external beam radiotherapy for localised prostate cancer. The patients were instructed to take magnesium oxide tablets during radiotherapy. They were also encouraged to avoid foods that might cause intestinal gas during radiotherapy. Gas accumulation in the rectum was graded into three classes by the same radiation oncologist. If no gas was seen in the rectum, it was classified as grade 0. A small amount of gas was classified as grade 1, whereas a marked amount of gas that required removal was classified as grade 2. Of the 2042 sets of MV images, grades 1 and 2 gas accumulation were seen in 332 (16%) and 156 (8%), respectively. By the trend test, gas accumulation significantly decreased towards the end of treatment (P=0.02 for grade 1 or 2 and P=0.02 for grade 2). On multivariate analysis, we did not identify any significant independent predictors for either baseline gas accumulation or gas reduction. Gas accumulation tended to decrease until the end of treatment. This tendency should be reconfirmed by other institutions.

  7. Direct localised measurement of electrical resistivity profile in rat and embryonic chick retinas using a microprobe

    Directory of Open Access Journals (Sweden)

    Harald van Lintel

    2010-01-01

    Full Text Available We report an alternative technique to perform a direct and local measurement of electrical resistivities in a layered retinal tissue. Information on resistivity changes along the depth in a retina is important for modelling retinal stimulation by retinal prostheses. Existing techniques for resistivity-depth profiling have the drawbacks of a complicated experimental setup, a less localised resistivity probing and/or lower stability for measurements. We employed a flexible microprobe to measure local resistivity with bipolar impedance spectroscopy at various depths in isolated rat and chick embryo retinas for the first time. Small electrode spacing permitted high resolution measurements and the probe flexibility contributed to stable resistivity profiling. The resistivity was directly calculated based on the resistive part of the impedance measured with the Peak Resistance Frequency (PRF methodology. The resistivity-depth profiles for both rat and chick embryo models are in accordance with previous mammalian and avian studies in literature. We demonstrate that the measured resistivity at each depth has its own PRF signature. Resistivity profiles obtained with our setup provide the basis for the construction of an electric model of the retina. This model can be used to predict variations in parameters related to retinal stimulation and especially in the design and optimisation of efficient retinal implants.

  8. Location service for wireless network using improved RSS-based cellular localisation

    Science.gov (United States)

    Fayaz, Sara; Sarrafian, Sara

    2014-06-01

    Value-added services, especially in mobile environments, have recently become the key component of making more profit and attracting more subscribers. One of the most commonly used such service is location-based advertiser services. The main issue which should be considered in providing such services is determining the position of the mobile terminals precisely. In this paper, one pattern recognition localisation method based on the signal strength appropriated for implementing a location-based service is presented. The main aim is to introduce some practical solutions to decrease error and computational load and also eliminate the necessity of updating the database. Practical results illustrate high accuracy of this technique and its suitability to apply in such services. The mean error declines to 9.7 m and mean error corresponding to CDF = 67% and CDF = 95% are less than 11 m and 23 m, respectively. We also present a location-based advertising service, in which the customer's interests and local time are considered, in order to enhance the efficiency and individualism of this service.

  9. Three novel proteins co-localise with polyhydroxybutyrate (PHB) granules in Rhodospirillum rubrum S1.

    Science.gov (United States)

    Narancic, Tanja; Scollica, Elisa; Cagney, Gerard; O'Connor, Kevin E

    2018-04-01

    Polyhydroxybutyrate (PHB), a biodegradable polymer accumulated by bacteria is deposited intracellularly in the form of inclusion bodies often called granules. The granules are supramolecular complexes harbouring a varied number of proteins on their surface, which have specific but incompletely characterised functions. By comparison with other organisms that produce biodegradable polymers, only two phasins have been described to date for Rhodosprillum rubrum, raising the possibility that more await discovery. Using a comparative proteomics strategy to compare the granules of wild-type R. rubrum with a PHB-negative mutant housing artificial PHB granules, we identified four potential PHB granules' associated proteins. These were: Q2RSI4, an uncharacterised protein; Q2RWU9, annotated as an extracellular solute-binding protein; Q2RQL4, annotated as basic membrane lipoprotein; and Q2RQ51, annotated as glucose-6-phosphate isomerase. In silico analysis revealed that Q2RSI4 harbours a Phasin_2 family domain and shares low identity with a single-strand DNA-binding protein from Sphaerochaeta coccoides. Fluorescence microscopy found that three proteins Q2RSI4, Q2EWU9 and Q2RQL4 co-localised with PHB granules. This work adds three potential new granule associated proteins to the repertoire of factors involved in bacterial storage granule formation, and confirms that proteomics screens are an effective strategy for discovery of novel granule associated proteins.

  10. Positioning and aligning CNTs by external magnetic field to assist localised epoxy cure

    Directory of Open Access Journals (Sweden)

    Ariu G.

    2016-01-01

    Full Text Available This work focuses on the generation of conductive networks through the localised alignment of nano fillers, such as multi-walled carbon nanotubes (MWCNTs. The feasibility of alignment and positioning of functionalised MWCNTs by external DC magnetic fields was investigated. The aim of this manipulation is to enhance resin curing through AC induction heating due to hysteresis losses from the nanotubes. Experimental analyses focused on in-depth assessment of the nanotube functionalisation, processing and characterisation of magnetic, rheological and cure kinetics properties of the MWCNT solution. The study has shown that an external magnetic field has great potential for positioning and alignment of CNTs. The study demonstrated potential for creating well-ordered architectures with an unprecedented level of control of network geometry. Magnetic characterisation indicated cobalt-plated nanotubes to be the most suitable candidate for magnetic alignment due to their high magnetic sensitivity. Epoxy/metal-plated CNT nanocomposite systems were validated by thermal analysis as induction heating mediums. The curing process could therefore be optimised by the use of dielectric resins. This study offers a first step towards the proof of concept of this technique as a novel repair technology.

  11. Positioning and aligning CNTs by external magnetic field to assist localised epoxy cure

    Science.gov (United States)

    Ariu, G.; Hamerton, I.; Ivanov, D.

    2016-01-01

    This work focuses on the generation of conductive networks through the localised alignment of nano fillers, such as multi-walled carbon nanotubes (MWCNTs). The feasibility of alignment and positioning of functionalised MWCNTs by external DC magnetic fields was investigated. The aim of this manipulation is to enhance resin curing through AC induction heating due to hysteresis losses from the nanotubes. Experimental analyses focused on in-depth assessment of the nanotube functionalisation, processing and characterisation of magnetic, rheological and cure kinetics properties of the MWCNT solution. The study has shown that an external magnetic field has great potential for positioning and alignment of CNTs. The study demonstrated potential for creating well-ordered architectures with an unprecedented level of control of network geometry. Magnetic characterisation indicated cobalt-plated nanotubes to be the most suitable candidate for magnetic alignment due to their high magnetic sensitivity. Epoxy/metal-plated CNT nanocomposite systems were validated by thermal analysis as induction heating mediums. The curing process could therefore be optimised by the use of dielectric resins. This study offers a first step towards the proof of concept of this technique as a novel repair technology.

  12. The duplicated genes database: identification and functional annotation of co-localised duplicated genes across genomes.

    Directory of Open Access Journals (Sweden)

    Marion Ouedraogo

    Full Text Available BACKGROUND: There has been a surge in studies linking genome structure and gene expression, with special focus on duplicated genes. Although initially duplicated from the same sequence, duplicated genes can diverge strongly over evolution and take on different functions or regulated expression. However, information on the function and expression of duplicated genes remains sparse. Identifying groups of duplicated genes in different genomes and characterizing their expression and function would therefore be of great interest to the research community. The 'Duplicated Genes Database' (DGD was developed for this purpose. METHODOLOGY: Nine species were included in the DGD. For each species, BLAST analyses were conducted on peptide sequences corresponding to the genes mapped on a same chromosome. Groups of duplicated genes were defined based on these pairwise BLAST comparisons and the genomic location of the genes. For each group, Pearson correlations between gene expression data and semantic similarities between functional GO annotations were also computed when the relevant information was available. CONCLUSIONS: The Duplicated Gene Database provides a list of co-localised and duplicated genes for several species with the available gene co-expression level and semantic similarity value of functional annotation. Adding these data to the groups of duplicated genes provides biological information that can prove useful to gene expression analyses. The Duplicated Gene Database can be freely accessed through the DGD website at http://dgd.genouest.org.

  13. Primary user localisation and uplink resource allocation in orthogonal frequency division multiple access cognitive radio systems

    KAUST Repository

    Nam, Haewoon

    2015-05-21

    In cognitive radio networks, secondary users (SUs) can share spectrum with primary users (PUs) under the condition that no interference is caused to the PUs. To evaluate the interference imposed to the PUs, the cognitive systems discussed in the literature usually assume that the channel state information (CSI) of the link from a secondary transmitter to a primary receiver (interference link) is known at the secondary transmitter. However, this assumption may often be impractical in cognitive radio systems, since the PUs need to be oblivious to the presence of the SUs. The authors first discuss PU localisation and then introduce an uplink resource allocation algorithm for orthogonal frequency division multiple access-based cognitive radio systems, where relative location information between primary and SUs is used instead of CSI of the interference link to estimate the interference. Numerical and simulation results show that it is indeed effective to use location information as a part of resource allocation and thus a near-optimal capacity is achieved. © The Institution of Engineering and Technology 2015.

  14. Higher phylogeny of frugivorous flies (Diptera, Tephritidae, Dacini): localised partition conflicts and a novel generic classification.

    Science.gov (United States)

    Virgilio, Massimiliano; Jordaens, Kurt; Verwimp, Christophe; White, Ian M; De Meyer, Marc

    2015-04-01

    The phylogenetic relationships within and among subtribes of the fruit fly tribe Dacini (Ceratitidina, Dacina, Gastrozonina) were investigated by sequencing four mitochondrial and one nuclear gene fragment. Bayesian, maximum likelihood and maximum parsimony analyses were implemented on two datasets. The first, aiming at obtaining the strongest phylogenetic signal (yet, having lower taxon coverage), consisted of 98 vouchers and 2338 concatenated base pairs (bp). The second, aiming at obtaining the largest taxonomic coverage (yet, providing lower resolution), included 159 vouchers and 1200 concatenated bp. Phylogenetic relationships inferred by different tree reconstruction methods were largely congruent and showed a general agreement between concatenated tree topologies. Yet, local conflicts in phylogenetic signals evidenced a number of critical sectors in the phylogeny of Dacini fruit flies. All three Dacini subtribes were recovered as monophyletic. Yet, within the subtribe Ceratitidina only Perilampsis and Capparimyia formed well-resolved monophyletic groups while Ceratitis and Trirhithrum did not. Carpophthoromyia was paraphyletic because it included Trirhithrum demeyeri and Ceratitis connexa. Complex phylogenetic relationships and localised conflict in phylogenetic signals were observed within subtribe Dacina with (a) Dacus, (b) Bactrocera (Zeugodacus) and (c) all other Bactrocera species forming separate clades. The subgenus Bactrocera (Zeugodacus) is therefore raised to generic rank (Zeugodacus Hendel stat. nov.). Additionally, Bactrocera subgenera grouped under the Zeugodacus group should be considered under new generic combinations. Although there are indications that Zeugodacus and Dacus are sister groups, the exact relationship between Zeugodacus stat. nov., Dacus and Bactrocera still needs to be properly resolved. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Prediction and comparison of down-link electric field and uplink localised SAR values for realistic indoor wireless planning

    International Nuclear Information System (INIS)

    Plets, David; Joseph, Wout; Aerts, Sam; Vanhecke, Kris; Vermeeren, Guenter; Martens, Luc

    2014-01-01

    In this paper, for the first time a heuristic network calculator for both whole-body exposure due to indoor base station antennas or access points (down-link exposure) and localised exposure due to the mobile device (uplink exposure) in indoor wireless networks is presented. As an application, three phone call scenarios are investigated (Universal Mobile Telecommunications System (UMTS) macro-cell, UMTS femto-cell and WiFi voice-over-IP) and compared with respect to the electric-field strength and localised specific absorption rate (SAR) distribution. Prediction models are created and successfully validated with an accuracy of 3 dB. The benefits of the UMTS power control mechanisms are demonstrated. However, dependent on the macro-cell connection quality and on the user's average phone call connection time, also the macro-cell solution might be preferential from an exposure point of view for the considered scenario. (authors)

  16. Simplified segmented human models for whole body and localised SAR evaluation of 20 MHz to 6 GHz electromagnetic field exposures

    International Nuclear Information System (INIS)

    Wu, T.; Shao, Q.; Yang, L.

    2013-01-01

    The digital human model is a key element in evaluating the electromagnetic field (EMF) exposure. This paper proposes the application of simplified segmented human models for EMF exposure compliance evaluation with the whole body and the localised limits. The method is based on the fact that most of the EMF power absorption is concentrated in several major tissues. Two kinds of human models were simply (the proposed method) and precisely segmented from two sets of whole body magnetic resonance imaging (MRI) scanned images. The whole body average-specific absorption rate (WBA-SAR) and the peak localised SAR averaging over 10 g tissues for the two kinds of models are calculated for various exposure configurations. The results confirmed the efficiency and the validity of the proposed method. The application as evaluating the MRI radiofrequency EMF exposure is also discussed in the paper. (authors)

  17. Allogeneic transplantation for multiple myeloma: late relapse may occur as localised lytic lesion/plasmacytoma despite ongoing molecular remission.

    Science.gov (United States)

    Byrne, J L; Fairbairn, J; Davy, B; Carter, I G; Bessell, E M; Russell, N H

    2003-02-01

    Allogeneic SCT for myeloma may be curative for young patients, but its role remains controversial because of a reported high TRM in some series. Since 1991, we have performed 25 allografts for myeloma using fully matched sibling donors. Of the 18 evaluable patients, 13 achieved CR at a median time of 2.5 months post-transplant. The five patients who were not in CR when assessed at 3 months received a short course of alpha-interferon and four subsequently achieved CR with this approach at a median of 82 days. One patient who failed to respond to IFN went on to achieve CR after four doses of DLI therapy, thus giving an overall CR rate of 72%. Seven patients have relapsed at a median of 4.7 years post-transplant (range 1.38-7.7 years) including two patients who had received IFN therapy. In five of these cases, relapse has been as a localised area of bone disease or isolated plasmacytoma with no evidence of marrow involvement by trephine biopsy or molecular analysis. All patients with localised relapse were treated with local radiotherapy +/-DLI and four are currently disease free despite two patients having had further treatment for a second localised lesion. Six patients died of TRM (24%) and the OS at 8 years is currently 69% with an EFS of 26%. These results suggest that allogeneic SCT for myeloma can be carried out with an acceptable TRM and a high CR rate. However, late relapses as localised disease may be a frequent finding and may represent foci of myeloma not eradicated by the conditioning. The use of pretransplant MRI scanning and top-up radiotherapy to involved areas may be useful in preventing this type of relapse.

  18. Zinc fingers 1, 2, 5 and 6 of transcriptional regulator, PRDM4, are required for its nuclear localisation

    Energy Technology Data Exchange (ETDEWEB)

    Tunbak, Hale, E-mail: h.tunbak@ucl.ac.uk [The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT (United Kingdom); Georgiou, Christiana, E-mail: christiana.georgiou.10@ucl.ac.uk [The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT (United Kingdom); Guan, Cui, E-mail: c.guan@qmul.ac.uk [School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS (United Kingdom); Richardson, William David, E-mail: w.richardson@ucl.ac.uk [The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT (United Kingdom); Chittka, Alexandra, E-mail: a.chittka@ucl.ac.uk [The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT (United Kingdom)

    2016-05-27

    PRDM4 is a member of the PRDM family of transcriptional regulators which control various aspects of cellular differentiation and proliferation. PRDM proteins exert their biological functions both in the cytosol and the nucleus of cells. All PRDM proteins are characterised by the presence of two distinct structural motifs, the PR/SET domain and the zinc finger (ZF) motifs. We previously observed that deletion of all six zinc fingers found in PRDM4 leads to its accumulation in the cytosol, whereas overexpressed full length PRDM4 is found predominantly in the nucleus. Here, we investigated the requirements for single zinc fingers in the nuclear localisation of PRDM4. We demonstrate that ZF's 1, 2, 5 and 6 contribute to the accumulation of PRDM4 in the nucleus. Their effect is additive as deleting either ZF1-2 or ZF 5–6 redistributes PRDM4 protein from being almost exclusively nuclear to cytosolic and nuclear. We investigated the potential mechanism of nuclear shuttling of PRDM4 via the importin α/β-mediated pathway and find that PRDM4 nuclear targeting is independent of α/β-mediated nuclear import. -- Highlights: •Zinc fingers 1, 2, 5, and 6 are necessary for efficient nuclear localisation of PRDM4. •Zinc fingers 3 and 4 are dispensable for nuclear localisation of PRDM4. •Zinc knuckle is dispensable for nuclear localisation of PRDM4. •PRDM4 nuclear transport is independent of importin α/β-mediated pathway of nuclear import.

  19. FCJ-171 Expectations denied: Fan and industry conflict around the localisation of the Japanese video game Yakuza 3

    Directory of Open Access Journals (Sweden)

    Craig Norris

    2014-12-01

    Full Text Available Online fan cultures provides researchers with a space to observe and analyse the development and establishment of fan participation with media properties. The visibility of, and zealous postings by, fans on online forums offers a valuable opportunity to explore what happens when fans feel their expectations are being denied or limited by creator or industry actions. This article examines the fallout around the localisation of the Japanese video game Yakuza 3 into the West in 2010.

  20. A discussion on the merits and limitations of using drive-by monitoring to detect localised damage in a bridge

    Science.gov (United States)

    Hester, David; González, Arturo

    2017-06-01

    Given the large number of bridges that currently have no instrumentation, there are obvious advantages in monitoring the condition of a bridge by analysing the response of a vehicle crossing it. As a result, the last two decades have seen a rise in the research attempting to solve the problem of identifying damage in a bridge from vehicle measurements. This paper examines the theoretical feasibility and practical limitations of a drive-by system in identifying damage associated to localised stiffness losses. First, the nature of the damage feature that is sought within the vehicle response needs to be characterized. For this purpose, the total vehicle response is considered to be made of 'static' and 'dynamic' components, and where the bridge has experienced a localised loss in stiffness, an additional 'damage' component. Understanding the nature of this 'damage' component is crucial to have an informed discussion on how damage can be identified and localised. Leveraging this new understanding, the authors propose a wavelet-based drive-by algorithm. By comparing the effect of the 'damage' component to other key effects defining the measurements such as 'vehicle speed', the 'road profile' and 'noise' on a wavelet contour plot, it is possible to establish if there is a frequency range where drive-by can be successful. The algorithm uses then specific frequency bands to improve the sensitivity to damage with respect to limitations imposed by Vehicle-Bridge vibrations. Recommendations on the selection of the mother wavelet and frequency band are provided. Finally, the paper discusses the impact of noise and road profile on the ability of the approach to identify damage and how periodic measurements can be effective at monitoring localised stiffness changes.

  1. The utility of 99mTc-sestamibi scintigraphy in the localisation of parathyroid adenomas in primary hyperparathyroidism.

    LENUS (Irish Health Repository)

    Glynn, N

    2012-02-01

    BACKGROUND: There are conflicting data in the literature about the sensitivity of sestamibi scintigraphy in parathyroid tumour localisation in primary hyperparathyroidism (PHPT). AIM: We aimed to evaluate the overall sensitivity of this modality in parathyroid tumour localisation and to determine clinical and biochemical factors which influence sensitivity of this method. METHODS: We performed a retrospective review of 57 patients with a biochemical diagnosis of PHPT who had sestamibi scintigraphy performed. RESULTS: The sensitivity of sestamibi scanning was 56% in whole group and 63% in those without nodular thyroid disease. Among the patients with confirmed single gland disease (biochemical cure after surgical removal of a single adenoma), sensitivity was 71%. A positive scan was associated with younger age, greater adenoma weight and higher pre-operative serum calcium. Concordance between the sestamibi and neck ultrasonography was 92% accurate in pre-operative tumour localisation. CONCLUSION: Sestamibi scintigraphy was more likely to be positive in younger patients without nodular thyroid disease who have larger parathyroid adenomas with more severe hyperparathyroidism.

  2. Quantitative elemental localisation in leaves and stems of nickel hyperaccumulating shrub Hybanthusfloribundus subsp. floribundus using micro-PIXE spectroscopy

    International Nuclear Information System (INIS)

    Kachenko, Anthony G; Singh, Balwant; Bhatia, Naveen P; Siegele, Rainer

    2008-01-01

    Hybanthusfloribundus (Lindl.) F.Muell. subsp. floribundus is a native Australian nickel (Ni) hyperaccumulating shrub and a promising species for rehabilitation and phytoremediation of Ni tailings. Spatial localisation and quantification of Ni in leaf and stem tissues of H.floribundus subsp. floribundus was studied using micro-proton-induced X-ray emission (micro-PIXE) spectroscopy. Young plants, grown in a potting mix under controlled glasshouse conditions were exposed to Ni concentrations of 0 and 26 mM kg -1 for 20 weeks. Leaf and stem samples were hand-sectioned and freeze-dried prior to micro-PIXE analysis. Elemental distribution maps of leaves revealed Ni concentration of 7800 mg kg -1 dry weight (DW) in whole leaf sections, which was identical to the bulk tissue analysis. Elemental maps showed that Ni was preferentially localised in the adaxial epidermis (10,000 mg kg -1 DW) and reached a maximum of up to 10,000 mg kg -1 DW in the leaf margin. Freeze-dried stem sections from the same plants contained lower Ni than leaf tissues (1800 mg kg -1 versus 7800 mg kg -1 DW, respectively), however did not resolve a clear pattern of compartmentalisation across different anatomical regions. Our results suggest localisation in epidermal cells is an important physiological mechanism involved in Ni accumulation and tolerance in leaves of H.floribundus subsp. floribundus

  3. Localisation and quantification of alkali-labile sites in human spermatozoa by DNA breakage detection-fluorescence in situ hybridisation.

    Science.gov (United States)

    Cortés-Gutiérrez, E I; Dávila-Rodríguez, M I; Cerda-Flores, R M; Fernández, J L; López-Fernández, C; Aragón Tovar, A R; Gosálvez, J

    2015-03-01

    The localisation and quantification of constitutive alkali-labile sites (ALSs) were investigated using a protocol of DNA breakage detection plus fluorescence in situ hybridisation (DBD-FISH) and alkaline single-cell gel electrophoresis (SCGE or comet assay), in spermatozoa of infertile and fertile men. Semen samples from 10 normozoospermic patients undergoing infertility treatment and 10 fertile men were included in this study. ALSs were localised and quantified by DBD-FISH. The region most sensitive to alkali treatment in human spermatozoa was located in the basal region of the head. ALSs were more frequent in spermatozoa of infertile men than in those of fertile men. These results were confirmed by SCGE comet assays. In conclusion, the most intense localisation of hybridisation signals in human spermatozoa, representing the highest density of constitutive ALSs, was not randomly distributed and was predominantly located in the base of the head. Moreover, infertile men presented with an increase in ALS frequency. Further studies are necessary to determine the association between ALS, sperm chromatin organisation and infertility. © 2014 Blackwell Verlag GmbH.

  4. An evaluation of South Africa's public-private partnership for the localisation of vaccine research, manufacture and distribution.

    Science.gov (United States)

    Walwyn, David R; Nkolele, Adolph T

    2018-03-27

    Public-private partnerships (PPPs), widely used as a means of leveraging the skills, expertise and resources of the private sector to mutual advantage, were similarly adopted by South Africa to support public sector delivery. This study has evaluated one such partnership, namely the Biovac Institute, which was established in 2003 to cover vaccine research and development, manufacturing, and supply. The initiative was highly unusual given that it attempted to combine all three aspects in a single PPP. The research has followed a concurrent mixed methods approach. In the quantitative study, data for prices and product volumes were extracted from secondary data sources and used to calculate the economic cost and value-for-money of the PPP. Simultaneously, a qualitative study was undertaken in which a number of key stakeholders were interviewed using a semi-structured questionnaire on their perceptions of the PPP's value. The institute earns a premium on the procurement cost of a broad range of vaccines required by the South African National Department of Health for its immunisation programme, the net value of which was US$85.7 million over the period 2010 to 2014. These funds were used to finance the institute's operations, including vaccine research, distribution and quality control. Capital expenditure to support the establishment of facilities for laboratory testing, packaging and labelling, filling, formulation and, finally, active pharmaceutical ingredient manufacture, approximately US$40 million in total, had to be secured through loans and grants. According to the respondents in the qualitative survey, the principal benefit of the PPP has been the uninterrupted supply of vaccines and the ability to respond quickly to vaccine shortages. The main disadvantages appear to have been a slow and ineffectual establishment of a vaccine manufacturing centre and, initially, a limited ability to negotiate highly competitive vaccine prices. Overall, it is concluded that a

  5. Integration of microplasma and microfluidic technologies for localised microchannel surface modification

    Science.gov (United States)

    Szili, Endre J.; Al-Bataineh, Sameer A.; Priest, Craig; Gruner, Philipp J.; Ruschitzka, Paul; Bradley, James W.; Ralston, John; Steele, David A.; Short, Robert D.

    2011-12-01

    In this paper we describe the spatial surface chemical modification of bonded microchannels through the integration of microplasmas into a microfluidic chip (MMC). The composite MMC comprises an array of precisely aligned electrodes surrounding the gas/fluid microchannel. Pairs of electrodes are used to locally ignite microplasmas inside the microchannel. Microplasmas, comprising geometrically confined microscopic electrically-driven gas discharges, are used to spatially functionalise the walls of the microchannels with proteins and enzymes down to scale lengths of 300 μm inside 50 μm-wide microchannels. Microchannels in poly(dimethylsiloxane) (PDMS) or glass were used in this study. Protein specifically adsorbed on to the regions inside the PDMS microchannel that were directly exposed to the microplasma. Glass microchannels required pre-functionalisation to enable the spatial patterning of protein. Firstly, the microchannel wall was functionalised with a protein adhesion layer, 3-aminopropyl-triethoxysilane (APTES), and secondly, a protein blocking agent (bovine serum albumin, BSA) was adsorbed onto APTES. The functionalised microchannel wall was then treated with an array of spatially localised microplasmas that reduced the blocking capability of the BSA in the region that had been exposed to the plasma. This enabled the functionalisation of the microchannel with an array of spatially separated protein. As an alternative we demonstrated the feasibility of depositing functional thin films inside the MMC by spatially plasma depositing acrylic acid and 1,7-octadiene within the microchannel. This new MMC technology enables the surface chemistry of microchannels to be engineered with precision, which is expected to broaden the scope of lab-on-a-chip type applications.

  6. Sustainable City Regions: Re-localising Landscapes in a Globalising World

    Directory of Open Access Journals (Sweden)

    Robert Thayer Jnr

    2004-06-01

    Full Text Available This paper emphasises physical, technological and economic variables in a globalising world, and how they might influence local economies and local landscapes. With the expected 'big rollover' in demand versus supply of oil in the next decade, the scale of the landscape will change in response to a permanent rise in the price of transportation and shipping fuels. Air travel will become less accessible, as will shipping of high mass, low value-added materials and goods. This will necessitate the re-establishment of more local supplies and shorter transport distances for people and goods, and for the first time in human history the perceived size of the world will expand. In response, the 'grain' of the landscape will become finer. More people will populate the rural landscape, while cities and towns will become more compact. The landscape is influenced by the three major operative technological systems (matter, energy and information. While the depletion of oil will greatly affect matter and energy, it will have less influence on information, which is relatively immune from entropic thermodynamic effects. While source-to-end-use distances will shorten, world per-capita energy expenditures will fall, and more local goods will be created and consumed, it remains to be seen whether this contraction in the scale of the instrumental landscape will be matched by more localised ownership, or by continued globalisation of corporate systems of production and distribution. Assuming the former is preferable, the paper concludes by suggesting that the bioregion, or natural 'life place', is the appropriate location for the protection of biodiversity, sustained use of resources, and identity and life satisfaction of local inhabitants.

  7. Impairment of CDKL5 nuclear localisation as a cause for severe infantile encephalopathy.

    Science.gov (United States)

    Rosas-Vargas, H; Bahi-Buisson, N; Philippe, C; Nectoux, J; Girard, B; N'Guyen Morel, M A; Gitiaux, C; Lazaro, L; Odent, S; Jonveaux, P; Chelly, J; Bienvenu, T

    2008-03-01

    Mutations in the human X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been shown to cause infantile spasms as well as Rett syndrome-like phenotype. To date, fewer than 20 different mutations have been reported. So far, no clear genotype-phenotype correlation has been established. We screened the entire coding region of CDKL5 in 151 affected girls with a clinically heterogeneous phenotype ranging from encephalopathy with epilepsy to atypical Rett syndrome by denaturing high liquid performance chromatography and direct sequencing, and we identified three novel missense mutations located in catalytic domain (p.Ala40Val, p.Arg65Gln, p.Leu220Pro). Segregation analysis showed that p.Arg65Gln was inherited from the healthy father, which rules out the involvement of CDKL5 in the aetiology of the phenotype in this patient. However, the de novo occurrence was shown for p.Ala40Val and p.Leu220Pro. The p.Ala40Val mutation was observed in two unrelated patients and represented the first recurrent mutation in the CDKL5 gene. For the two de novo mutations, we analysed the cellular localisation of the wild-type and CDKL5 mutants by transfection experiments. We showed that the two CDKL5 mutations cause mislocalisation of the mutant CDKL5 proteins in the cytoplasm. Interestingly these missense mutations that result in a mislocalisation of the CDKL5 protein are associated with severe developmental delay which was apparent within the first months of life characterised by early and generalised hypotonia, and autistic features, and as well as early infantile spasms.

  8. Reduction in expression of the benign AR transcriptome is a hallmark of localised prostate cancer progression.

    Science.gov (United States)

    Stuchbery, Ryan; Macintyre, Geoff; Cmero, Marek; Harewood, Laurence M; Peters, Justin S; Costello, Anthony J; Hovens, Christopher M; Corcoran, Niall M

    2016-05-24

    Despite the importance of androgen receptor (AR) signalling to prostate cancer development, little is known about how this signalling pathway changes with increasing grade and stage of the disease. To explore changes in the normal AR transcriptome in localised prostate cancer, and its relation to adverse pathological features and disease recurrence. Publically accessible human prostate cancer expression arrays as well as RNA sequencing data from the prostate TCGA. Tumour associated PSA and PSAD were calculated for a large cohort of men (n=1108) undergoing prostatectomy. We performed a meta-analysis of the expression of an androgen-regulated gene set across datasets using Oncomine. Differential expression of selected genes in the prostate TCGA database was probed using the edgeR Bioconductor package. Changes in tumour PSA density with stage and grade were assessed by Student's t-test, and its association with biochemical recurrence explored by Kaplan-Meier curves and Cox regression. Meta-analysis revealed a systematic decline in the expression of a previously identified benign prostate androgen-regulated gene set with increasing tumour grade, reaching significance in nine of 25 genes tested despite increasing AR expression. These results were confirmed in a large independent dataset from the TCGA. At the protein level, when serum PSA was corrected for tumour volume, significantly lower levels were observed with increasing tumour grade and stage, and predicted disease recurrence. Lower PSA secretion-per-tumour-volume is associated with increasing grade and stage of prostate cancer, has prognostic relevance, and reflects a systematic perturbation of androgen signalling.

  9. Assimilation of flood extent data with 2D flood inundation models for localised intense rainfall events

    Science.gov (United States)

    Neal, J. C.; Wood, M.; Bermúdez, M.; Hostache, R.; Freer, J. E.; Bates, P. D.; Coxon, G.

    2017-12-01

    Remote sensing of flood inundation extent has long been a potential source of data for constraining and correcting simulations of floodplain inundation. Hydrodynamic models and the computing resources to run them have developed to the extent that simulation of flood inundation in two-dimensional space is now feasible over large river basins in near real-time. However, despite substantial evidence that there is useful information content within inundation extent data, even from low resolution SAR such as that gathered by Envisat ASAR in wide swath mode, making use of the information in a data assimilation system has proved difficult. He we review recent applications of the Ensemble Kalman Filter (EnKF) and Particle Filter for assimilating SAR data, with a focus on the River Severn UK and compare these with complementary research that has looked at the internal error sources and boundary condition errors using detailed terrestrial data that is not available in most locations. Previous applications of the EnKF to this reach have focused on upstream boundary conditions as the source of flow error, however this description of errors was too simplistic for the simulation of summer flood events where localised intense rainfall can be substantial. Therefore, we evaluate the introduction of uncertain lateral inflows to the ensemble. A further limitation of the existing EnKF based methods is the need to convert flood extent to water surface elevations by intersecting the shoreline location with a high quality digital elevation model (e.g. LiDAR). To simplify this data processing step, we evaluate a method to directly assimilate inundation extent as a EnKF model state rather than assimilating water heights, potentially allowing the scheme to be used where high-quality terrain data are sparse.

  10. Quantitative study of luminescence optical tomography. Application to sources localisation in molecular imaging

    International Nuclear Information System (INIS)

    Boffety, Matthieu

    2010-01-01

    Molecular imaging is a major modality in the field of preclinical research. Among the existing methods, techniques based on optical detection of visible or near infrared radiation are the most recent and are mainly represented by luminescence optical tomography techniques. These methods allow for 3D characterization of a biological medium by reconstructing maps of concentration or localisation of luminescent beacons sensitive to biological and chemical processes at the molecular or cellular scale. Luminescence optical tomography is based on a model of light propagation in tissues, a protocol for acquiring surface signal and a numerical inversion procedure used to reconstruct the parameters of interest. This thesis is structured around these three axes and provides an answer to each problem. The main objective of this study is to introduce and present the tools to evaluate the theoretical performances of optical tomography methods. One of its major outcomes is the realisation of experimental tomographic reconstructions from images acquired by an optical imager designed for 2D planar imaging and developed by the company Quidd. In a first step we develop the theory of transport in scattering medium to establish the concept on which our work will rely. We present two different propagation models as well as resolution methods and theoretical difficulties associated with them. In a second part we introduce the statistical tools used to characterise tomographic systems. We define and apply a procedure to simple situations in luminescence optical tomography. The last part of this work presents the development of an inversion procedure. After introducing the theoretical framework we validate the procedure from numerical data before successfully applying it to experimental measurements. (author) [fr

  11. Localised uptake and extraction of Calcium/sup 45/ in dinoflagellate nuclei: An autoradiographic study

    Energy Technology Data Exchange (ETDEWEB)

    Sigee, D.C.

    1983-01-01

    The uptake of Ca/sup 45/ into cells of the dinoflagellate Glenodinium foliaceum was investigated using insoluble compound light microscope autoradiography. The distribution of silver grains showed marked localisation to the dinocaryotic nucleus, with a random scatter of grains over the surrounding protoplasm (cytoplasm and supernumerary nucleus). Correction of grain counts for lateral sensitisation from the dinocaryotic nucleus indicated an isotope concentration 16-32 times greater in this organelle compared to the rest of the cell. Cells labelled for varying periods of time showed differences in the pattern of Ca/sup 45/ uptake throughout the sample populations, but no increase in the mean level of uptake per cell. This would suggest a rapid incorporation of isotope within 1-2 hours, with little subsequent uptake. The presence of high levels of label after processing with both additive (glutaraldehyde, paraformaldehyde) and coagulative (acetic alcohol) fixatives indicated that the retention of Ca/sup 45/ in these preparations was not simply a fixation artefact. Although the isotope did not appear to be suitable for (high resolution) electron microscope autoradiography, the intranuclear site of incorporation was demonstrated indirectly using a buffer extraction technique. Prolonged treatment with phosphate buffer resulted in a large scale loss of label from both cytoplasm and dinocaryotic nucleus. The latter appeared to show specific correlation with the loss of (protein) matrix from the chromosomes - as observed under both light and electron microscopy, with no apparent change in either nucleolus or nucleoplasm. This would suggest that incorporated Ca/sup 45/ in the nucleus was largely confined to the condensed chromatin, where it was combined with the acidic proteins which make up the bulk of the chromatin matrix. The results obtained in this investigation are related to previous studies involving X-ray microanalysis and uptake of Ni/sup 63/.

  12. Safety assessment and improvement of Ignalina NPP against downcomer ruptures outside Accident Localisation System

    International Nuclear Information System (INIS)

    Rimkevicius, S.; Urbonavicius, E.

    2002-01-01

    Accident Localisation System (ALS) of Ignalina NPP is a pressure suppression type confinement, designed to prevent the release of contaminated steam-water mixture to the environment in case of Loss-of-Coolant Accident (LOCA). One of the peculiarities of Ignalina NPP with RBMK-1500 reactors is that not all of the reactor coolant circuit is enclosed within ALS. Some part of downcomers, that connect Drum Separator (DS) and suction header of main circulation pump is located outside ALS. In case of downcomer rupture in DS compartment the discharge is not confined, but flows to the environment through the safety panels installed in the ceiling of DS compartments. Numerous safety analyses were performed to assess the safety of Ignalina NPP against downcomer break outside ALS, and results were used for different applications in order to improve the safety of the plant. This paper presents the overview of the performed analyses, recommendations raised and safety improvements made to enhance the safety level of NPP. One of the applications is to present the recommendations for safety improvement if maximal allowable pressure limits are exceeded. The calculations results demonstrate that in the case of two downcomers rupture in drum separators compartment the maximum permissible pressure in the reactor hall could be exceeded. The knock-out panels from the reactor hall to the environment were recommended and installed for reactor hall overpressure protection. The evaluation of the drainage system efficiency from DS compartments was performed. In this case the especial attention was paid to analyse the water collection and drainage system behaviour in long term after postulated breaks. The analysis results showed that the modernization of the drainage system prevents the accumulation of the released water in the compartments even in the case of two downcomer pipes ruptures, and decreases the release of radioactive fission products (FP) to the environment.(author)

  13. An electrospun polydioxanone patch for the localisation of biological therapies during tendon repair

    Directory of Open Access Journals (Sweden)

    O Hakimi

    2012-10-01

    Full Text Available Rotator cuff tendon pathology is thought to account for 30-70 % of all shoulder pain. For cases that have failed conservative treatment, surgical re-attachment of the tendon to the bone with a non-absorbable suture is a common option. However, the failure rate of these repairs is high, estimated at up to 75 %. Studies have shown that in late disease stages the tendon itself is extremely degenerate, with reduced cell numbers and poor matrix organisation. Thus, it has been suggested that adding biological factors such as platelet rich plasma (PRP and mesenchymal stem cells could improve healing. However, the articular capsule of the glenohumeral joint and the subacromial bursa are large spaces, and injecting beneficial factors into these sites does not ensure localisation to the area of tendon damage.Thus, the aim of this study was to develop a biocompatible patch for improving the healing rates of rotator cuff repairs. The patch will create a confinement around the repair area and will be used to guide injections to the vicinity of the surgical repair.Here, we characterised and tested a preliminary prototype of the patch utilising in vitro tools and primary tendon-derived cells, showing exceptional biocompatibility despite rapid degradation, improved cell attachment and that cells could migrate across the patch towards a chemo-attractant. Finally, we showed the feasibility of detecting the patch using ultrasound and injecting liquid into the confinement ex vivo. There is a potential for using this scaffold in the surgical repair of interfaces such as the tendon insertion in the rotator cuff, in conjunction with beneficial factors.

  14. Towards understanding edge localised mode mitigation by resonant magnetic perturbations in MAST

    Energy Technology Data Exchange (ETDEWEB)

    Chapman, I. T.; Kirk, A.; Ham, C. J.; Harrison, J. R.; Liu, Y. Q.; Saarelma, S.; Scannell, R.; Thornton, A. J.; Team, MAST [EURATOM/CCFE Fusion Association, Culham Science Centre, Abingdon, Oxfordshire OX14 3DB (United Kingdom); Becoulet, M.; Orain, F. [Association Euratom/CEA, CEA Cadarache, IRFM, F-13108, St. Paul-lez-Durance (France); Cooper, W. A. [CRPP, Association EURATOM/Confédération Suisse, EPFL, 1015 Lausanne (Switzerland); Pamela, S. [IIFS-PIIM. Aix Marseille Université—CNRS, 13397 Marseille Cedex 20 (France)

    2013-05-15

    Type-I Edge Localised Modes (ELMs) have been mitigated in MAST through the application of n=3,4, and 6 resonant magnetic perturbations. For each toroidal mode number of the non-axisymmetric applied fields, the frequency of the ELMs has been increased significantly, and the peak heat flux on the divertor plates reduced commensurately. This increase in ELM frequency occurs despite a significant drop in the edge pressure gradient, which would be expected to stabilise the peeling-ballooning modes thought to be responsible for type-I ELMs. Various mechanisms which could cause a destabilisation of the peeling-ballooning modes are presented, including pedestal widening, plasma rotation braking, three dimensional corrugation of the plasma boundary, and the existence of radially extended lobe structures near to the X-point. This leads to a model aimed at resolving the apparent dichotomy of ELM control, which is to say ELM suppression occurring due to the pedestal pressure reduction below the peeling-ballooning stability boundary, whilst the reduction in pressure can also lead to ELM mitigation, which is ostensibly a destabilisation of peeling-ballooning modes. In the case of ELM mitigation, the pedestal broadening, 3d corrugation, or lobes near the X-point degrade ballooning stability so much that the pedestal recovers rapidly to cross the new stability boundary at lower pressure more frequently, whilst in the case of suppression, the plasma parameters are such that the particle transport reduces the edge pressure below the stability boundary, which is only mildly affected by negligible rotation braking, small edge corrugation or short, broad lobe structures.

  15. Optimising EEG-fMRI for Localisation of Focal Epilepsy in Children.

    Directory of Open Access Journals (Sweden)

    Maria Centeno

    Full Text Available Early surgical intervention in children with drug resistant epilepsy has benefits but requires using tolerable and minimally invasive tests. EEG-fMRI studies have demonstrated good sensitivity for the localization of epileptic focus but a poor yield although the reasons for this have not been systematically addressed. While adults EEG-fMRI studies are performed in the "resting state"; children are commonly sedated however, this has associated risks and potential confounds. In this study, we assessed the impact of the following factors on the tolerability and results of EEG-fMRI in children: viewing a movie inside the scanner; movement; occurrence of interictal epileptiform discharges (IED; scan duration and design efficiency. This work's motivation is to optimize EEG-fMRI parameters to make this test widely available to paediatric population.Forty-six children with focal epilepsy and 20 controls (6-18 underwent EEG-fMRI. For two 10 minutes sessions subjects were told to lie still with eyes closed, as it is classically performed in adult studies ("rest sessions", for another two sessions, subjects watched a child friendly stimulation i.e. movie ("movie sessions". IED were mapped with EEG-fMRI for each session and across sessions. The resulting maps were classified as concordant/discordant with the presumed epileptogenic focus for each subject.Movement increased with scan duration, but the movie reduced movement by ~40% when played within the first 20 minutes. There was no effect of movie on the occurrence of IED, nor in the concordance of the test. Ability of EEG-fMRI to map the epileptogenic region was similar for the 20 and 40 minute scan durations. Design efficiency was predictive of concordance.A child friendly natural stimulus improves the tolerability of EEG-fMRI and reduces in-scanner movement without having an effect on IED occurrence and quality of EEG-fMRI maps. This allowed us to scan children as young as 6 and obtain localising

  16. Evaluation of a three-dimensional ultrasound localisation system incorporating probe pressure correction for use in partial breast irradiation.

    Science.gov (United States)

    Harris, E J; Symonds-Taylor, R; Treece, G M; Gee, A H; Prager, R W; Brabants, P; Evans, P M

    2009-10-01

    This work evaluates a three-dimensional (3D) freehand ultrasound-based localisation system with new probe pressure correction for use in partial breast irradiation. Accuracy and precision of absolute position measurement was measured as a function of imaging depth (ID), object depth, scanning direction and time using a water phantom containing crossed wires. To quantify the improvement in accuracy due to pressure correction, 3D scans of a breast phantom containing ball bearings were obtained with and without pressure. Ball bearing displacements were then measured with and without pressure correction. Using a single scan direction (for all imaging depths), the mean error was <1.3 mm, with the exception of the wires at 68.5 mm imaged with an ID of 85 mm, which gave a mean error of -2.3 mm. Precision was greater than 1 mm for any single scan direction. For multiple scan directions, precision was within 1.7 mm. Probe pressure corrections of between 0 mm and 2.2 mm have been observed for pressure displacements of 1.1 mm to 4.2 mm. Overall, anteroposterior position measurement accuracy increased from 2.2 mm to 1.6 mm and to 1.4 mm for the two opposing scanning directions. Precision is comparable to that reported for other commercially available ultrasound localisation systems, provided that 3D image acquisition is performed in the same scan direction. The existing temporal calibration is imperfect and a "per installation" calibration would further improve the accuracy and precision. Probe pressure correction was shown to improve the accuracy and will be useful for the localisation of the excision cavity in partial breast radiotherapy.

  17. Three-dimensional Acoustic Localisation via Directed Movements of a Two-dimensional Model of the Lizard Peripheral Auditory System

    DEFF Research Database (Denmark)

    Shaikh, Danish; Kjær Schmidt, Michael

    2017-01-01

    of the acoustic target with respect to one plane of rotation. A multi-layer perceptron neural network is trained via supervised learning to translate the combination of the two measurements into an estimate of the relative location of the acoustic target in terms of its azimuth and elevation. The acoustic...... localisation performance of the system is evaluated in simulation for noiseless as well as noisy sinusoidal auditory signals with a 20 dB signal-to-noise ratio for four different sound frequencies of 1450 Hz, 1650 Hz, 1850 Hz and 2050 Hz that span the response frequency range of the peripheral auditory model...

  18. Localisation of light and spectral broadening of femtosecond laser pulses in a fibre with a minimal-microstructure cladding

    International Nuclear Information System (INIS)

    Zheltikov, Aleksei M; Zhou, Ping; Temnov, V V; Tarasevitch, A P; Linde, D von der; Kondrat'ev, Yu N; Shevandin, V S; Dukel'skii, K V; Khokhlov, A V; Bagayev, S N; Smirnov, Valerii B

    2002-01-01

    Microstructure optical fibres with a cladding consisting of a single cycle of air holes and the minimum core diameter of 1 μm have been fabricated and studied. Guided modes supported by this fibre are characterised by a high light localisation degree and display the C 6ν point-group spatial symmetry of the transverse field distribution. A high refractive index step between the core and the cladding in the created fibres strongly confines the light field in the fibre core. The spectral broadening of low-power femtosecond laser pulses in the fibre of this type is experimentally studied. (nonlinear optical phenomena)

  19. On the non-existence of totally localised intersections of D3/D5 branes in type IIB SUGRA

    Energy Technology Data Exchange (ETDEWEB)

    Patino, Leonardo [Department of Mathematical Sciences, University of Durham, Durham, DH1 3LE (United Kingdom); Smith, Douglas [Department of Mathematical Sciences, University of Durham, Durham, DH1 3LE (United Kingdom)

    2005-04-01

    In the present paper we study the most general configuration of intersecting D3/D5 branes in type IIB supergravity satisfying Poincare invariance in the directions common to the branes and SO(3) symmetry in the totally perpendicular directions. The form of these configurations is greatly restricted by the Killing spinor equations and the equations of motion, which among other things, force the Ramond-Ramond scalar to be zero and do not permit the existence of totally localised intersections of this kind.

  20. On the non-existence of totally localised intersections of D3/D5 branes in type IIB SUGRA

    International Nuclear Information System (INIS)

    Patino, Leonardo; Smith, Douglas

    2005-01-01

    In the present paper we study the most general configuration of intersecting D3/D5 branes in type IIB supergravity satisfying Poincare invariance in the directions common to the branes and SO(3) symmetry in the totally perpendicular directions. The form of these configurations is greatly restricted by the Killing spinor equations and the equations of motion, which among other things, force the Ramond-Ramond scalar to be zero and do not permit the existence of totally localised intersections of this kind

  1. Altered localisation of the copper efflux transporters ATP7A and ATP7B associated with cisplatin resistance in human ovarian carcinoma cells

    International Nuclear Information System (INIS)

    Kalayda, Ganna V; Wagner, Christina H; Buß, Irina; Reedijk, Jan; Jaehde, Ulrich

    2008-01-01

    Copper homeostasis proteins ATP7A and ATP7B are assumed to be involved in the intracellular transport of cisplatin. The aim of the present study was to assess the relevance of sub cellular localisation of these transporters for acquired cisplatin resistance in vitro. For this purpose, localisation of ATP7A and ATP7B in A2780 human ovarian carcinoma cells and their cisplatin-resistant variant, A2780cis, was investigated. Sub cellular localisation of ATP7A and ATP7B in sensitive and resistant cells was investigated using confocal fluorescence microscopy after immunohistochemical staining. Co-localisation experiments with a cisplatin analogue modified with a carboxyfluorescein-diacetate residue were performed. Cytotoxicity of the fluorescent cisplatin analogue in A2780 and A2780cis cells was determined using an MTT-based assay. The significance of differences was analysed using Student's t test or Mann-Whitney test as appropriate, p values of < 0.05 were considered significant. In the sensitive cells, both transporters are mainly localised in the trans-Golgi network, whereas they are sequestrated in more peripherally located vesicles in the resistant cells. Altered localisation of ATP7A and ATP7B in A2780cis cells is likely to be a consequence of major abnormalities in intracellular protein trafficking related to a reduced lysosomal compartment in this cell line. Changes in sub cellular localisation of ATP7A and ATP7B may facilitate sequestration of cisplatin in the vesicular structures of A2780cis cells, which may prevent drug binding to genomic DNA and thereby contribute to cisplatin resistance. Our results indicate that alterations in sub cellular localisation of transport proteins may contribute to cisplatin resistance in vitro. Investigation of intracellular protein localisation in primary tumour cell cultures and tumour tissues may help to develop markers of clinically relevant cisplatin resistance. Detection of resistant tumours in patients may in turn

  2. Altered localisation of the copper efflux transporters ATP7A and ATP7B associated with cisplatin resistance in human ovarian carcinoma cells

    Directory of Open Access Journals (Sweden)

    Reedijk Jan

    2008-06-01

    Full Text Available Abstract Background Copper homeostasis proteins ATP7A and ATP7B are assumed to be involved in the intracellular transport of cisplatin. The aim of the present study was to assess the relevance of sub cellular localisation of these transporters for acquired cisplatin resistance in vitro. For this purpose, localisation of ATP7A and ATP7B in A2780 human ovarian carcinoma cells and their cisplatin-resistant variant, A2780cis, was investigated. Methods Sub cellular localisation of ATP7A and ATP7B in sensitive and resistant cells was investigated using confocal fluorescence microscopy after immunohistochemical staining. Co-localisation experiments with a cisplatin analogue modified with a carboxyfluorescein-diacetate residue were performed. Cytotoxicity of the fluorescent cisplatin analogue in A2780 and A2780cis cells was determined using an MTT-based assay. The significance of differences was analysed using Student's t test or Mann-Whitney test as appropriate, p values of Results In the sensitive cells, both transporters are mainly localised in the trans-Golgi network, whereas they are sequestrated in more peripherally located vesicles in the resistant cells. Altered localisation of ATP7A and ATP7B in A2780cis cells is likely to be a consequence of major abnormalities in intracellular protein trafficking related to a reduced lysosomal compartment in this cell line. Changes in sub cellular localisation of ATP7A and ATP7B may facilitate sequestration of cisplatin in the vesicular structures of A2780cis cells, which may prevent drug binding to genomic DNA and thereby contribute to cisplatin resistance. Conclusion Our results indicate that alterations in sub cellular localisation of transport proteins may contribute to cisplatin resistance in vitro. Investigation of intracellular protein localisation in primary tumour cell cultures and tumour tissues may help to develop markers of clinically relevant cisplatin resistance. Detection of resistant tumours

  3. Comparison of the time taken for localised breast surgery pre- and post-introduction of intra-operative digital specimen mammography.

    Science.gov (United States)

    Carraro do Nascimento, Vinicius; Bourke, Anita G

    2018-02-01

    More than half of the patients with an impalpable malignant breast lesion have a mammographically detected and imaged-guided localisation, which can be technically challenging for the breast surgeon. Specimen imaging is used to confirm successful excision of the localised index lesion and has improved the operating list efficiency resulting in a higher number of excisions per surgical list. The aim of this study was to evaluate whether introducing IDSM (intra-operative digital specimen mammography) saved operation time for localised breast surgery. A single-centre retrospective review was undertaken to compare the operation time (from incision to wound closure) taken for excision of 114 consecutive image-guided localised impalpable breast lesions, performed using departmental specimen radiography (DSR), 6 months prior to the introduction of IDSM (Hologic, Trident ® ) in March 2013, with the theatre time taken for excision of 121 consecutive image-guided localised impalpable breast lesions in the 6 months following introduction of IDSM. There was no significant difference in mean surgical time, which were 47.8 (±27.3) minutes in the CSR group and 48.8 (±25.7) minutes in the IDSM group. We were expecting to confirm a reduction in theatre time with the introduction of IDSM. Surprisingly, no difference in operating times was demonstrated. Factors that influenced the impact of IDSM included the proximity of the imaging department to the operating theatre. © 2017 The Royal Australian and New Zealand College of Radiologists.

  4. Current strategies for monitoring men with localised prostate cancer lack a strong evidence base: observational longitudinal study.

    Science.gov (United States)

    Metcalfe, C; Tilling, K; Davis, M; Lane, J A; Martin, R M; Kynaston, H; Powell, P; Neal, D E; Hamdy, F; Donovan, J L

    2009-08-04

    The UK National Institute for Health and Clinical Excellence (NICE) guidance recommends conservative management of men with 'low-risk' localised prostate cancer, monitoring the disease using prostate-specific antigen (PSA) kinetics and re-biopsy. However, there is little evidence of the changes in PSA level that should alert to the need for clinical re-assessment. This study compares the alerts resulting from PSA kinetics and a novel longitudinal reference range approach, which incorporates age-related changes, during the monitoring of 408 men with localised prostate cancer. Men were monitored by regular PSA tests over a mean of 2.9 years, recording when a man's PSA doubling time fell below 2 years, PSA velocity exceeded 2 ng ml(-1) per year, or when his upper 10% reference range was exceeded. Prostate-specific antigen doubling time and PSA velocity alerted a high proportion of men initially but became unresponsive to changes with successive tests. Calculating doubling time using recent PSA measurements reduced the decline in response. The reference range method maintained responsiveness to changes in PSA level throughout the monitoring. The increasing unresponsiveness of PSA kinetics is a consequence of the underlying regression model. Novel methods are needed for evaluation in cohorts currently being managed by monitoring. Meanwhile, the NICE guidance should be cautious.

  5. Sentinel node localisation using pre-operative lymphoscintigraphy and intraoperative gamma probe in early oral cavity cancer

    International Nuclear Information System (INIS)

    Ikram, M.; Akhtar, S.; Junaid, M.; Dhari, T.; Zaman, M.U.; Hussain, R.

    2013-01-01

    Objectives: To assess the diagnostic value of sentinel lymph node localisation using pre-operative lymphoscintigraphy and intra-operative gamma probe radio localisation in Pakistani patients suffering from early stage squamous cell carcinoma of the oral cavity. Methods: The prospective case series was conducted between September 2007 and April 2010 at the Aga Khan University Hospital, Karachi. It comprised patients with T1 and T2 oral cavity cancer with clinically and radiologically negative neck. Pre-operative lymphoscintigraphy was performed one day before surgery and intra-operative gamma probe was used to detect sentinel node. Final histo-pathological evaluation was taken as the gold standard. Results: The study comprised 42 patients: 32(76%) males and 10(24%) females. The primary tumour site was buccal mucosa in 25 (60%) patients, and tongue in 17 (40%). Sentinel lymph node was detected in 38 (90%) patients. On final histopathological identification, 7 (17%) patients had cancer in the neck nodes. In all patients with metastasis, sentinel lymph node technique correctly identified the involved neck level. None of the patients revealed metastasis in non-sentinel lymph nodes. Conclusion:Evidence suggested the use of sentinel node biopsy in patients with head and neck squamous cell carcinoma. (author)

  6. Localisation of deformations of the midfacial complex in subjects with class III malocclusions employing thin-plate spline analysis.

    Science.gov (United States)

    Singh, G D; McNamara, J A; Lozanoff, S

    1997-11-01

    This study determines deformations of the midface that contribute to a class III appearance, employing thinplate spline analysis. A total of 135 lateral cephalographs of prepubertal children of European-American descent with either class III malocclusions or a class I molar occlusion were compared. The cephalographs were traced and checked, and 7 homologous landmarks of the midface were identified and digitised. The data sets were scaled to an equivalent size and subjected to Procrustes analysis. These statistical tests indicated significant differences (P spline analysis indicated that both affine and nonaffine transformations contribute towards the total spline for the averaged midfacial configuration. For nonaffine transformations, partial warp 3 had the highest magnitude, indicating the large scale deformations of the midfacial configuration. These deformations affected the palatal landmarks, and were associated with compression of the midfacial complex in the anteroposterior plane predominantly. Partial warp 4 produced some vertical compression of the posterior aspect of the midfacial complex whereas partial warps 1 and 2 indicated localised shape changes of the maxillary alveolus region. large spatial-scale deformations therefore affect the midfacial complex in an anteroposterior axis, in combination with vertical compression and localised distortions. These deformations may represent a developmental diminution of the palatal complex anteroposteriorly that, allied with vertical shortening of midfacial height posteriorly, results in class III malocclusions with a retrusive midfacial profile.

  7. Hydrogen-induced strain localisation in oxygen-free copper in the initial stage of plastic deformation

    Science.gov (United States)

    Yagodzinskyy, Yuriy; Malitckii, Evgenii; Tuomisto, Filip; Hänninen, Hannu

    2018-03-01

    Single crystals of oxygen-free copper oriented to easy glide of dislocations were tensile tested in order to study the hydrogen effects on the strain localisation in the form of slip bands appearing on the polished specimen surface under tensile straining. It was found that hydrogen increases the plastic flow stress in Stage I of deformation. The dislocation slip localisation in the form of slip bands was observed and analysed using an online optical monitoring system and atomic force microscopy. The fine structure of the slip bands observed with AFM shows that they consist of a number of dislocation slip offsets which spacing in the presence of hydrogen is markedly reduced as compared to that in the hydrogen-free specimens. The tensile tests and AFM observations were accompanied with positron annihilation lifetime measurements showing that straining of pure copper in the presence of hydrogen results in free volume generation in the form of vacancy complexes. Hydrogen-enhanced free-volume generation is discussed in terms of hydrogen interactions with edge dislocation dipoles forming in double cross-slip of screw dislocations in the initial stage of plastic deformation of pure copper.

  8. Elevated p21-Activated Kinase 2 Activity Results in Anchorage-Independent Growth and Resistance to Anticancer Drug–Induced Cell Death

    Directory of Open Access Journals (Sweden)

    Jerry W. Marlin

    2009-03-01

    Full Text Available p21-Activated kinase 2 (PAK-2 seems to be a regulatory switch between cell survival and cell death signaling. We have shown previously that activation of full-length PAK-2 by Rac or Cdc42 stimulates cell survival, whereas caspase activation of PAK-2 to the proapoptotic PAK-2p34 fragment is involved in the cell death response. In this study, we present a role of elevated activity of full-length PAK-2 in anchorage-independent growth and resistance to anticancer drug–induced apoptosis of cancer cells. Hs578T human breast cancer cells that have low levels of PAK-2 activity were more sensitive to anticancer drug–induced apoptosis and showed higher levels of caspase activation of PAK-2 than MDA-MB435 and MCF-7 human breast cancer cells that have high levels of PAK-2 activity. To examine the role of elevated PAK-2 activity in breast cancer, we have introduced a conditionally active PAK-2 into Hs578T human breast cells. Conditional activation of PAK-2 causes loss of contact inhibition and anchorage-independent growth of Hs578T cells. Furthermore, conditional activation of PAK-2 suppresses activation of caspase 3, caspase activation of PAK-2, and apoptosis of Hs578T cells in response to the anticancer drug cisplatin. Our data suggest a novel mechanism by which full-length PAK-2 activity controls the apoptotic response by regulating levels of activated caspase 3 and thereby its own cleavage to the proapoptotic PAK-2p34 fragment. As a result, elevated PAK-2 activity interrupts the apoptotic response and thereby causes anchorage-independent survival and growth and resistance to anticancer drug–induced apoptosis.

  9. Improvement of localised corrosion resistance of AISI 2205 Duplex Stainless Steel joints made by gas metal arc welding under electromagnetic interaction of low intensity

    Science.gov (United States)

    García-Rentería, M. A.; López-Morelos, V. H.; García-Hernández, R.; Dzib-Pérez, L.; García-Ochoa, E. M.; González-Sánchez, J.

    2014-12-01

    The resistance to localised corrosion of AISI 2205 duplex stainless steel plates joined by Gas Metal Arc Welding (GMAW) under the effect of electromagnetic interaction of low intensity (EMILI) was evaluated with sensitive electrochemical methods. Welds were made using two shielding gas mixtures: 98% Ar + 2% O2 (M1) and 97% Ar + 3% N2 (M2). Plates were welded under EMILI using the M1 gas with constant welding parameters. The modified microstructural evolution in the high temperature heat affected zone and at the fusion zone induced by application of EMILI during welding is associated with the increase of resistance to localised corrosion of the welded joints. Joints made by GMAW using the shielding gas M2 without the application of magnetic field presented high resistance to general corrosion but high susceptibility to undergo localised attack.

  10. Localisation of gluconeogenesis and tricarboxylic acid (TCA)-cycle enzymes and first functional analysis of the TCA cycle in Toxoplasma gondii.

    Science.gov (United States)

    Fleige, Tobias; Pfaff, Nils; Gross, Uwe; Bohne, Wolfgang

    2008-08-01

    The apicomplexan parasite Toxoplasma gondii displays some unusual localisations of carbohydrate converting enzymes, which is due to the presence of a vestigial, non-photosynthetic plastid, referred to as the apicoplast. It was recently demonstrated that the single pyruvate dehydrogenase complex (PDH) in T. gondii is exclusively localised inside the apicoplast but absent in the mitochondrion. This raises the question about expression, localisation and function of enzymes for the tricarboxylic acid (TCA)-cycle, which normally depends on PDH generated acetyl-CoA. Based on the expression and localisation of epitope-tagged fusion proteins, we show that all analysed TCA cycle enzymes are localised in the mitochondrion, including both isoforms of malate dehydrogenase. The absence of a cytosolic malate dehydrogenase suggests that a typical malate-aspartate shuttle for transfer of reduction equivalents is missing in T. gondii. We also localised various enzymes which catalyse the irreversible steps in gluconeogenesis to a cellular compartment and examined mRNA expression levels for gluconeogenesis and TCA cycle genes between tachyzoites and in vitro bradyzoites. In order to get functional information on the TCA cycle for the parasite energy metabolism, we created a conditional knock-out mutant for the succinyl-CoA synthetase. Disruption of the sixth step in the TCA cycle should leave the biosynthetic parts of the cycle intact, but prevent FADH2 production. The succinyl-CoA synthetase depletion mutant displayed a 30% reduction in growth rate, which could be restored by supplementation with 2 microM succinate in the tissue culture medium. The mitochondrial membrane potential in these parasites was found to be unaltered. The lack of a more severe phenotype suggests that a functional TCA cycle is not essential for T. gondii replication and for maintenance of the mitochondrial membrane potential.

  11. An assessment of the importance ofexposure routes to the uptake and internal localisation of fluorescent nanoparticles in zebrafish (Danio rerio), using light sheet microscopy

    DEFF Research Database (Denmark)

    Skjolding, Lars Michael; Ašmonaitė, G; Jølck, Rasmus Irming

    2017-01-01

    A major challenge in nanoecotoxicology is finding suitable methods to determine the uptake and localisation of nanoparticles on a whole-organism level. Some uptake methods have been associated with artefacts induced by sample preparation, including staining for electron microscopy. This study used...... light sheet microscopy (LSM) to define the uptake and localisation of fluorescently labelled nanoparticles in living organisms with minimal sample preparation. Zebrafish (Danio rerio) were exposed to fluorescent gold nanoparticles (Au NPs) and fluorescent polystyrene NPs via aqueous or dietary exposure...

  12. Radiation hardness of the Si-Si0/sub 2/ interface and carrier localisation in the inversion layer

    Energy Technology Data Exchange (ETDEWEB)

    Pepper, M [Cambridge Univ. (UK). Cavendish Lab.

    1977-08-28

    The results of low temperature measurements of inversion layer conductance suggest that there are positive and negative charges in the form of pairs close to the Si-Si0/sub 2/ interface. The negative centres trap holes created in the Si0/sub 2/ by the irradiation of MOS structures. The annealing treatments developed to 'harden' the interface, by minimising the hole trapping, are interpreted as resulting in a reduction in the total interfacial charge, which is not apparent from measurements of the net charge. It is suggested that the dependence of the localisation effects on the substrate bias may be useful as a diagnostic, pre-irradiation, screening test. By using various interface preparation treatments an exercise in interface engineering is now possible, in which the total interfacial charge, and the form of the random fluctuations in potential, can be altered in a controllable manner.

  13. Gene expression, cellular localisation and function of glutamine synthetase isozymes in wheat (Triticum aestivum L.)

    DEFF Research Database (Denmark)

    Bernard, Stéphanie M.; Møller, Anders Laurell Blom; Dionisio, Giuseppe

    2008-01-01

    ). Phylogenetic analysis showed that the wheat GS sub-families together with the GS genes from other monocotyledonous species form four distinct clades. Immunolocalisation studies in leaves, stems and rachis in plants at flowering showed GS protein to be present in parenchyma, phloem companion and perifascicular......We present the first cloning and study of glutamine synthetase (GS) genes in wheat (Triticum aestivum L.). Based on sequence analysis, phylogenetic studies and mapping data, ten GS sequences were classified into four sub-families: GS2 (a, b and c), GS1 (a, b and c), GSr (1 and 2) and GSe (1 and 2...... sheath cells. In situ localisation confirmed that GS1 transcripts were present in the perifascicular sheath cells whilst those for GSr were confined to the vascular cells. Studies of the expression and protein profiles showed that all GS sub-families were differentially expressed in the leaves, peduncle...

  14. Nonlinear network model analysis of vibrational energy transfer and localisation in the Fenna-Matthews-Olson complex

    Science.gov (United States)

    Morgan, Sarah E.; Cole, Daniel J.; Chin, Alex W.

    2016-11-01

    Collective protein modes are expected to be important for facilitating energy transfer in the Fenna-Matthews-Olson (FMO) complex of photosynthetic green sulphur bacteria, however to date little work has focussed on the microscopic details of these vibrations. The nonlinear network model (NNM) provides a computationally inexpensive approach to studying vibrational modes at the microscopic level in large protein structures, whilst incorporating anharmonicity in the inter-residue interactions which can influence protein dynamics. We apply the NNM to the entire trimeric FMO complex and find evidence for the existence of nonlinear discrete breather modes. These modes tend to transfer energy to the highly connected core pigments, potentially opening up alternative excitation energy transfer routes through their influence on pigment properties. Incorporating localised modes based on these discrete breathers in the optical spectra calculations for FMO using ab initio site energies and excitonic couplings can substantially improve their agreement with experimental results.

  15. Attention-induced deactivations in very low frequency EEG oscillations: differential localisation according to ADHD symptom status.

    Directory of Open Access Journals (Sweden)

    Samantha J Broyd

    Full Text Available BACKGROUND: The default-mode network (DMN is characterised by coherent very low frequency (VLF brain oscillations. The cognitive significance of this VLF profile remains unclear, partly because of the temporally constrained nature of the blood oxygen-level dependent (BOLD signal. Previously we have identified a VLF EEG network of scalp locations that shares many features of the DMN. Here we explore the intracranial sources of VLF EEG and examine their overlap with the DMN in adults with high and low ADHD ratings. METHODOLOGY/PRINCIPAL FINDINGS: DC-EEG was recorded using an equidistant 66 channel electrode montage in 25 adult participants with high- and 25 participants with low-ratings of ADHD symptoms during a rest condition and an attention demanding Eriksen task. VLF EEG power was calculated in the VLF band (0.02 to 0.2 Hz for the rest and task condition and compared for high and low ADHD participants. sLORETA was used to identify brain sources associated with the attention-induced deactivation of VLF EEG power, and to examine these sources in relation to ADHD symptoms. There was significant deactivation of VLF EEG power between the rest and task condition for the whole sample. Using s-LORETA the sources of this deactivation were localised to medial prefrontal regions, posterior cingulate cortex/precuneus and temporal regions. However, deactivation sources were different for high and low ADHD groups: In the low ADHD group attention-induced VLF EEG deactivation was most significant in medial prefrontal regions while for the high ADHD group this deactivation was predominantly localised to the temporal lobes. CONCLUSIONS/SIGNIFICANCE: Attention-induced VLF EEG deactivations have intracranial sources that appear to overlap with those of the DMN. Furthermore, these seem to be related to ADHD symptom status, with high ADHD adults failing to significantly deactivate medial prefrontal regions while at the same time showing significant attenuation of

  16. Intraoperative radioguidance with a portable gamma camera: a novel technique for laparoscopic sentinel node localisation in urological malignancies

    International Nuclear Information System (INIS)

    Vermeeren, L.; Valdes Olmos, R.A.; Vogel, W.V.; Sivro, F.; Hoefnagel, C.A.; Meinhardt, W.; Bex, A.; Poel, H.G. van der; Horenblas, S.

    2009-01-01

    Our aim was to assess the feasibility of intraoperative radioguidance with a portable gamma camera during laparoscopic sentinel node (SN) procedures in urological malignancies. We evaluated the use of the intraoperative portable gamma camera in 20 patients: 16 patients with prostate carcinoma (PCC), 2 patients with renal cell carcinoma (RC) and 2 patients with testicular cancer (TC). Intra/peritumoural injection of 99m Tc-nanocolloid ( 99m Tc) was followed by planar lymphoscintigraphy, SPECT/CT and marking of SN levels. Before laparoscopy a 125 I seed was fixed on the laparoscopic gamma probe as a pointer of SN seeking. The portable gamma camera was set to display the 99m Tc signal for SN localisation and the 125 I signal for SN seeking. Matching of these signals on screen indicated exact SN localisation, and consequently this SN was removed. The mean injected dose was 218 MBq in PCC, 228 MBq in RC and 88 MBq in TC. Pelvic SN were visualised in all PCC patients, with uncommonly located SN in seven patients. SN metastases were found in seven patients (one in a uncommonly located SN). Both RC patients and TC patients had para-aortic SN, which were all tumour free. A total of 59 SN were removed. The portable gamma camera enabled real-time SN display/identification in 18 patients (90%). The use of a portable gamma camera in combination with a laparoscopic gamma probe incorporates intraoperative real-time imaging with improved SN identification in urological malignancies. This procedure might also be useful for SN identification of other deep draining malignancies. (orig.)

  17. Intraoperative radioguidance with a portable gamma camera: a novel technique for laparoscopic sentinel node localisation in urological malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Vermeeren, L.; Valdes Olmos, R.A.; Vogel, W.V.; Sivro, F.; Hoefnagel, C.A. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Meinhardt, W.; Bex, A.; Poel, H.G. van der; Horenblas, S. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Urology, Amsterdam (Netherlands)

    2009-07-15

    Our aim was to assess the feasibility of intraoperative radioguidance with a portable gamma camera during laparoscopic sentinel node (SN) procedures in urological malignancies. We evaluated the use of the intraoperative portable gamma camera in 20 patients: 16 patients with prostate carcinoma (PCC), 2 patients with renal cell carcinoma (RC) and 2 patients with testicular cancer (TC). Intra/peritumoural injection of {sup 99m}Tc-nanocolloid ({sup 99m}Tc) was followed by planar lymphoscintigraphy, SPECT/CT and marking of SN levels. Before laparoscopy a {sup 125}I seed was fixed on the laparoscopic gamma probe as a pointer of SN seeking. The portable gamma camera was set to display the {sup 99m}Tc signal for SN localisation and the {sup 125}I signal for SN seeking. Matching of these signals on screen indicated exact SN localisation, and consequently this SN was removed. The mean injected dose was 218 MBq in PCC, 228 MBq in RC and 88 MBq in TC. Pelvic SN were visualised in all PCC patients, with uncommonly located SN in seven patients. SN metastases were found in seven patients (one in a uncommonly located SN). Both RC patients and TC patients had para-aortic SN, which were all tumour free. A total of 59 SN were removed. The portable gamma camera enabled real-time SN display/identification in 18 patients (90%). The use of a portable gamma camera in combination with a laparoscopic gamma probe incorporates intraoperative real-time imaging with improved SN identification in urological malignancies. This procedure might also be useful for SN identification of other deep draining malignancies. (orig.)

  18. An assessment of the importance ofexposure routes to the uptake and internal localisation of fluorescent nanoparticles in zebrafish (Danio rerio), using light sheet microscopy

    DEFF Research Database (Denmark)

    Skjolding, Lars Michael; Ašmonaitė, G; Jølck, Rasmus Irming

    2017-01-01

    A major challenge in nanoecotoxicology is finding suitable methods to determine the uptake and localisation of nanoparticles on a whole-organism level. Some uptake methods have been associated with artefacts induced by sample preparation, including staining for electron microscopy. This study use...

  19. Game Localisation as Software-Mediated Cultural Experience: Shedding Light on the Changing Role of Translation in Intercultural Communication in the Digital Age

    Science.gov (United States)

    O'Hagan, Minako

    2015-01-01

    In this rapidly technologising age translation practice has been undergoing formidable changes with the implication that there is a need to expand the disciplinary scope of translation studies. Taking the case of game localisation this article problematises the role of translation as intercultural communication by focusing on cultural elements of…

  20. Improvement of localised corrosion resistance of AISI 2205 Duplex Stainless Steel joints made by gas metal arc welding under electromagnetic interaction of low intensity

    Energy Technology Data Exchange (ETDEWEB)

    García-Rentería, M.A., E-mail: crazyfim@gmail.com [Instituto de Investigación en Metalurgia y Materiales, Universidad Michoacana de San Nicolás de Hidalgo, A.P. 888, CP 58000, Morelia, Michoacán (Mexico); López-Morelos, V.H., E-mail: vhlopez@umich.mx [Instituto de Investigación en Metalurgia y Materiales, Universidad Michoacana de San Nicolás de Hidalgo, A.P. 888, CP 58000, Morelia, Michoacán (Mexico); García-Hernández, R., E-mail: rgarcia@umich.mx [Instituto de Investigación en Metalurgia y Materiales, Universidad Michoacana de San Nicolás de Hidalgo, A.P. 888, CP 58000, Morelia, Michoacán (Mexico); Dzib-Pérez, L., E-mail: luirdzib@uacam.mx [Centre for Corrosion Research, Autonomous University of Campeche, Av. Agustín Melgar s/n, Col. Buenavista, CP 24039, Campeche, Cam (Mexico); García-Ochoa, E.M., E-mail: emgarcia@uacam.mx [Centre for Corrosion Research, Autonomous University of Campeche, Av. Agustín Melgar s/n, Col. Buenavista, CP 24039, Campeche, Cam (Mexico); González-Sánchez, J., E-mail: jagonzal@uacam.mx [Centre for Corrosion Research, Autonomous University of Campeche, Av. Agustín Melgar s/n, Col. Buenavista, CP 24039, Campeche, Cam (Mexico)

    2014-12-01

    Highlights: • Electromagnetic interaction in welding improved localised corrosion resistance. • Electromagnetic interaction in welding enhanced γ/δ phase balance of DuplexSS. • Welding under Electromagnetic interaction repress formation and growth of detrimental phases. • Welds made with gas protection (2% O{sub 2} + 98% Ar) have better microstructural evolution during welding. - Abstract: The resistance to localised corrosion of AISI 2205 duplex stainless steel plates joined by Gas Metal Arc Welding (GMAW) under the effect of electromagnetic interaction of low intensity (EMILI) was evaluated with sensitive electrochemical methods. Welds were made using two shielding gas mixtures: 98% Ar + 2% O{sub 2} (M1) and 97% Ar + 3% N{sub 2} (M2). Plates were welded under EMILI using the M1 gas with constant welding parameters. The modified microstructural evolution in the high temperature heat affected zone and at the fusion zone induced by application of EMILI during welding is associated with the increase of resistance to localised corrosion of the welded joints. Joints made by GMAW using the shielding gas M2 without the application of magnetic field presented high resistance to general corrosion but high susceptibility to undergo localised attack.

  1. Neurophysiological localisation of ulnar neuropathy at the elbow: validation of diagnostic criteria developed by a taskforce of the Danish Society of Clinical Neurophysiology

    DEFF Research Database (Denmark)

    Pugdahl, Kirsten; Beniczky, Sándor; Wanscher, Benedikte

    2017-01-01

    OBJECTIVE: This study validates consensus criteria for localisation of ulnar neuropathy at elbow (UNE) developed by a taskforce of the Danish Society of Clinical Neurophysiology and compares them to the existing criteria from the American Association of Neuromuscular and Electrodiagnostic Medicine...

  2. The localisation of treponemes and characterisation of the inflammatory infiltrate in skin biopsies from patients with primary or secondary syphilis, or early infectious yaws

    NARCIS (Netherlands)

    Engelkens, H. J.; ten Kate, F. J.; Judanarso, J.; Vuzevski, V. D.; van Lier, J. B.; Godschalk, J. C.; van der Sluis, J. J.; Stolz, E.

    1993-01-01

    To study the localisation of treponemes and to analyse the inflammatory infiltrate in biopsy specimens from patients with primary or secondary syphilis, or early infectious yaws. Skin biopsies originating from human lesions of primary (29x) or secondary (15x) syphilis (Rotterdam), or early yaws

  3. Localisation of relaxin peptides in the brain: comparative mapping of relaxin-R2 and the novel relaxin-R3 gene expression

    International Nuclear Information System (INIS)

    Burazin, T.C.D.; Macris, M.; Gundlach, A.L.; Tregear, G.W.

    2002-01-01

    Full text: Relaxin is a peptide hormone with known actions in the female reproductive tract that has also been identified in brain. Until recently, only one relaxin gene has been described in the rat and mouse. However, we have recently identified a new member of the relaxin gene family, relaxin gene-3, expressed in human, mouse and rat. Using [ 35 S]-labelled oligonucleotide probes and in situ hybridisation histochemistry, the current studies describe the distribution of mRNA encoding rat relaxin gene-1 (R1) and rat relaxin gene-3 (R3) in the adult rat brain. R1 mRNA was detected in several regions including the anterior olfactory nucleus, tenia tecta, orbital, frontal and piriform cortices, and in lower abundance in the hippocampus. In contrast, highly abundant expression of R3 mRNA was more restricted being present in the pars ventromedialis subdivision of the dorsal tegmental nucleus (vmDTg), with some low level expression in the hippocampus. Autoradiographic visualisation of [ 33 P]-labelled human relaxin binding sites revealed the presence of putative relaxin receptors in the DTg centralis and vmDTg, as well as in several forebrain areas previously identified. Studies are currently underway to investigate the activity-dependent regulation and developmental expression of relaxin transcripts, including the possible co-localisation of R3 mRNA with neurotransmitters such as GABA and 5- HT, and other peptides. These studies are consistent with an important role for these novel relaxin peptides in the rat central nervous system. Copyright (2002) Australian Neuroscience Society

  4. Detection Classification and Localisation of Marine Mammals Using the Passive Acoustic Capabilities of an LFAS System

    NARCIS (Netherlands)

    Robert, M.K.; IJsselmuide, S.P. van; Beerens, S.P.

    2004-01-01

    World-wide a concern is emerging about the influence of man-made sound on marine life and more particularly marine mammals, who fully depend on sound in their natural behaviour. High power active sonars systems like Low Frequency Active Sonar (LFAS) are at stake. These systems, designed for long

  5. Wolbachia lipoproteins: abundance, localisation and serology of Wolbachia peptidoglycan associated lipoprotein and the Type IV Secretion System component, VirB6 from Brugia malayi and Aedes albopictus.

    Science.gov (United States)

    Voronin, Denis; Guimarães, Ana F; Molyneux, Gemma R; Johnston, Kelly L; Ford, Louise; Taylor, Mark J

    2014-10-06

    Lipoproteins are the major agonists of Wolbachia-dependent inflammatory pathogenesis in filariasis and a validated target for drug discovery. Here we characterise the abundance, localisation and serology of the Wolbachia lipoproteins: Wolbachia peptidoglycan associated lipoprotein and the Type IV Secretion System component, VirB6. We used proteomics to confirm lipoprotein presence and relative abundance; fractionation, immunoblotting and confocal and electron immuno-microscopy for localisation and ELISA for serological analysis. Proteomic analysis of Brugia malayi adult female protein extracts confirmed the presence of two lipoproteins, previously predicted through bioinformatics: Wolbachia peptidoglycan associated lipoprotein (wBmPAL) and the Type IV Secretion System component, VirB6 (wBmVirB6). wBmPAL was among the most abundant Wolbachia proteins present in an extract of adult female worms with wBmVirB6 only detected at a much lower abundance. This differential abundance was reflected in the immunogold-labelling, which showed wBmPAL localised at numerous sites within the bacterial membranes, whereas wBmVirB6 was present as a single cluster on each bacterial cell and also located within the bacterial membranes. Immunoblotting of fractionated extracts confirmed the localisation of wBmPAL to membranes and its absence from cytosolic fractions of C6/36 mosquito cells infected with wAlbB. In whole worm mounts, antibody labelling of both lipoproteins were associated with Wolbachia. Serological analysis showed that both proteins were immunogenic and raised antibody responses in the majority of individuals infected with Wuchereria bancrofti. Two Wolbachia lipoproteins, wBmPAL and wBmVirB6, are present in extracts of Brugia malayi with wBmPAL among the most abundant of Wolbachia proteins. Both lipoproteins localised to bacterial membranes with wBmVirB6 present as a single cluster suggesting a single Type IV Secretory System on each Wolbachia cell.

  6. Expression of the glutathione enzyme system of human colon mucosa by localisation, gender and age.

    NARCIS (Netherlands)

    Hoensch, H.; Peters, W.H.M.; Roelofs, H.M.J.; Kirch, W.

    2006-01-01

    BACKGROUND: The glutathione S-transferases (GST) can metabolise endogenous and exogenous toxins and carcinogens by catalysing the conjugation of diverse electrophiles with reduced glutathione (GSH). Variations of GST enzyme activity could influence the susceptibility of developing cancers in certain

  7. Commerce électronique et localisation urbaine des activités commerciales

    OpenAIRE

    Alain Rallet

    2001-01-01

    The aim of the article is to study the impact of electronic commerce on the urban organization of commercial activities. Despite of the weak level of the present development of e-commerce, significant transformations are expected. Generally confined to on line sales, electronic commerce is here defined more widely as the process of partial digitalization of commercial functions. Any business activity can be analyzed as a hybrid set of physical infrastructures and virtual functions. This hybri...

  8. Glucose activates prenyltransferases in pancreatic islet {beta}-cells

    Energy Technology Data Exchange (ETDEWEB)

    Goalstone, Marc [Department of Medicine, University of Colorado, VA Medical Center, Denver, CO 80220 (United States); Kamath, Vasudeva [Department of Pharmaceutical Sciences, Wayne State University, VA Medical Center, Detroit, MI 48201 (United States); Kowluru, Anjaneyulu, E-mail: akowluru@med.wayne.edu [Department of Pharmaceutical Sciences, Wayne State University, VA Medical Center, Detroit, MI 48201 (United States)

    2010-01-01

    A growing body of evidence implicates small G-proteins [e.g., Cdc42 and Rac1] in glucose-stimulated insulin secretion [GSIS] in the islet {beta}-cell. These signaling proteins undergo post-translational modifications [e.g., prenylation] at their C-terminal cysteine residue and appear to be essential for the transport and fusion of insulin-containing secretory granules with the plasma membrane and the exocytotic secretion of insulin. However, potential regulation of the prenylating enzymes by physiological insulin secretogues [e.g., glucose] has not been investigated thus far. Herein, we report immunological localization, sub-cellular distribution and regulation of farnesyltransferases [FTases] and geranylgeranyltransferase [GGTase] by glucose in insulin-secreting INS 832/13 {beta}-cells and normal rat islets. Our findings suggest that an insulinotropic concentration of glucose [20 mM] markedly stimulated the expression of the {alpha}-subunits of FTase/GGTase-1, but not the {beta}-subunits of FTase or GGTase-1 without significantly affecting the predominantly cytosolic distribution of these holoenzymes in INS 832/13 cells and rodent islets. Under these conditions, glucose significantly stimulated [2.5- to 4.0-fold over basal] the activities of both FTase and GGTase-1 in both cell types. Together, these findings provide the first evidence to suggest that GSIS involves activation of the endogenous islet prenyltransferases by glucose, culminating in the activation of their respective G-protein substrates, which is necessary for cytoskeletal rearrangement, vesicular transport, fusion and secretion of insulin.

  9. Glucose activates prenyltransferases in pancreatic islet β-cells

    International Nuclear Information System (INIS)

    Goalstone, Marc; Kamath, Vasudeva; Kowluru, Anjaneyulu

    2010-01-01

    A growing body of evidence implicates small G-proteins [e.g., Cdc42 and Rac1] in glucose-stimulated insulin secretion [GSIS] in the islet β-cell. These signaling proteins undergo post-translational modifications [e.g., prenylation] at their C-terminal cysteine residue and appear to be essential for the transport and fusion of insulin-containing secretory granules with the plasma membrane and the exocytotic secretion of insulin. However, potential regulation of the prenylating enzymes by physiological insulin secretogues [e.g., glucose] has not been investigated thus far. Herein, we report immunological localization, sub-cellular distribution and regulation of farnesyltransferases [FTases] and geranylgeranyltransferase [GGTase] by glucose in insulin-secreting INS 832/13 β-cells and normal rat islets. Our findings suggest that an insulinotropic concentration of glucose [20 mM] markedly stimulated the expression of the α-subunits of FTase/GGTase-1, but not the β-subunits of FTase or GGTase-1 without significantly affecting the predominantly cytosolic distribution of these holoenzymes in INS 832/13 cells and rodent islets. Under these conditions, glucose significantly stimulated [2.5- to 4.0-fold over basal] the activities of both FTase and GGTase-1 in both cell types. Together, these findings provide the first evidence to suggest that GSIS involves activation of the endogenous islet prenyltransferases by glucose, culminating in the activation of their respective G-protein substrates, which is necessary for cytoskeletal rearrangement, vesicular transport, fusion and secretion of insulin.

  10. Steady-state acceptor fluorescence anisotropy imaging under evanescent excitation for visualisation of FRET at the plasma membrane.

    Directory of Open Access Journals (Sweden)

    Viviane Devauges

    Full Text Available We present a novel imaging system combining total internal reflection fluorescence (TIRF microscopy with measurement of steady-state acceptor fluorescence anisotropy in order to perform live cell Förster Resonance Energy Transfer (FRET imaging at the plasma membrane. We compare directly the imaging performance of fluorescence anisotropy resolved TIRF with epifluorescence illumination. The use of high numerical aperture objective for TIRF required correction for induced depolarization factors. This arrangement enabled visualisation of conformational changes of a Raichu-Cdc42 FRET biosensor by measurement of intramolecular FRET between eGFP and mRFP1. Higher activity of the probe was found at the cell plasma membrane compared to intracellularly. Imaging fluorescence anisotropy in TIRF allowed clear differentiation of the Raichu-Cdc42 biosensor from negative control mutants. Finally, inhibition of Cdc42 was imaged dynamically in live cells, where we show temporal changes of the activity of the Raichu-Cdc42 biosensor.

  11. The Photospheric Flow near the Flare Locations of Active Regions

    Indian Academy of Sciences (India)

    tribpo

    in the active regions along with few locations of upflows. The localised upflows are observed in the light bridges and emerging flux regions with different speeds (Beckers & Schroter 1969). The flow patterns of flare locations in the active regions are observed by using the tower vector magnetograph (TVM) of Marshall.

  12. Cohort profile: the TrueNTH Global Registry - an international registry to monitor and improve localised prostate cancer health outcomes.

    Science.gov (United States)

    Evans, Sue M; Millar, Jeremy L; Moore, Caroline M; Lewis, John D; Huland, Hartwig; Sampurno, Fanny; Connor, Sarah E; Villanti, Paul; Litwin, Mark S

    2017-11-28

    Globally, prostate cancer treatment and outcomes for men vary according to where they live, their race and the care they receive. The TrueNTH Global Registry project was established as an international registry monitoring care provided to men with localised prostate cancer (CaP). Sites with existing CaP databases in Movember fundraising countries were invited to participate in the international registry. In total, 25 Local Data Centres (LDCs) representing 113 participating sites across 13 countries have nominated to contribute to the project. It will collect a dataset based on the International Consortium for Health Outcome Measures (ICHOM) standardised dataset for localised CaP. A governance strategy has been developed to oversee registry operation, including transmission of reversibly anonymised data. LDCs are represented on the Project Steering Committee, reporting to an Executive Committee. A Project Coordination Centre and Data Coordination Centre (DCC) have been established. A project was undertaken to compare existing datasets, understand capacity at project commencement (baseline) to collect the ICHOM dataset and assist in determining the final data dictionary. 21/25 LDCs provided data dictionaries for review. Some ICHOM data fields were well collected (diagnosis, treatment start dates) and others poorly collected (complications, comorbidities). 17/94 (18%) ICHOM data fields were relegated to non-mandatory fields due to poor capture by most existing registries. Participating sites will transmit data through a web interface biannually to the DCC. Recruitment to the TrueNTH Global Registry-PCOR project will commence in late 2017 with sites progressively contributing reversibly anonymised data following ethical review in local regions. Researchers will have capacity to source deidentified data after the establishment phase. Quality indicators are to be established through a modified Delphi approach in later 2017, and it is anticipated that reports on

  13. Spatiotemporal dynamics of phosphorus release, oxygen consumption and greenhouse gas emissions after localised soil amendment with organic fertilisers

    Energy Technology Data Exchange (ETDEWEB)

    Christel, Wibke [Department for Plant and Environmental Sciences, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C (Denmark); Department of Commerce, Industry and Agriculture, Danish Environmental Protection Agency, 1401 Copenhagen C (Denmark); Zhu, Kun [Department for Plant and Environmental Sciences, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C (Denmark); College of Resources and Environmental Sciences, China Agricultural University, Beijing 100193 (China); Hoefer, Christoph [Rhizosphere Ecology and Biogeochemistry Group, Department of Forest and Soil Sciences, University of Natural Resources and Life Sciences, Vienna, Konrad-Lorenz-Strasse 24, 3430 Tulln (Austria); Kreuzeder, Andreas [Rhizosphere Ecology and Biogeochemistry Group, Department of Forest and Soil Sciences, University of Natural Resources and Life Sciences, Vienna, Konrad-Lorenz-Strasse 24, 3430 Tulln (Austria); Land Salzburg, Natur- und Umweltschutz, Gewerbe (Abteilung 5), Michael-Pacher-Straße 36, 5020 Salzburg (Austria); Santner, Jakob [Rhizosphere Ecology and Biogeochemistry Group, Department of Forest and Soil Sciences, University of Natural Resources and Life Sciences, Vienna, Konrad-Lorenz-Strasse 24, 3430 Tulln (Austria); Division of Agronomy, Department of Crop Sciences, University of Natural Resources and Life Sciences, Vienna, Konrad-Lorenz-Strasse 24, 3430 Tulln (Austria); Bruun, Sander; Magid, Jakob [Department for Plant and Environmental Sciences, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C (Denmark); Jensen, Lars Stoumann, E-mail: lsj@plen.ku.dk [Department for Plant and Environmental Sciences, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C (Denmark)

    2016-06-01

    Organic fertilisation inevitably leads to heterogeneous distribution of organic matter and nutrients in soil, i.e. due to uneven surface spreading or inhomogeneous incorporation. The resulting localised hotspots of nutrient application will induce various biotic and abiotic nutrient turnover processes and fixation in the residuesphere, giving rise to distinct differences in nutrient availability, soil oxygen content and greenhouse gas (GHG) production. In this study we investigated the spatiotemporal dynamics of the reaction of manure solids and manure solids char with soil, focusing on their phosphorus (P) availability, as current emphasis on improving societal P efficiency through recycling waste or bio-based fertilisers necessitates a sound understanding of their behaviour. Soil layers amended at a constant P application rate with either pig manure solids or char made from pig manure solids were incubated for three weeks between layers of non-amended, P-depleted soil. Spatial and temporal changes in and around the amendment layers were simultaneously investigated in this study using a sandwich sensor consisting of a planar oxygen optode and multi-element diffusive gradients in thin films (DGT) gels, combined with GHG emission measurements. After three weeks of incubation, the soil containing a layer amended with manure solids had a lower overall O{sub 2} content and had emitted significantly more CO{sub 2} than the non-amended control or the char-amended soil. The P availability from manure solids was initially higher than that from the char, but decreased over time, whereas from the char-amended layer P availability increased in the same period. In both treatments, increases in P availability were confined to the amended soil layer and did not greatly affect P availability in the directly adjacent soil layers during the three-week incubation. These results highlight the importance of placing organic P fertilisers close to where the plant roots will grow in

  14. Spatiotemporal dynamics of phosphorus release, oxygen consumption and greenhouse gas emissions after localised soil amendment with organic fertilisers

    International Nuclear Information System (INIS)

    Christel, Wibke; Zhu, Kun; Hoefer, Christoph; Kreuzeder, Andreas; Santner, Jakob; Bruun, Sander; Magid, Jakob; Jensen, Lars Stoumann

    2016-01-01

    Organic fertilisation inevitably leads to heterogeneous distribution of organic matter and nutrients in soil, i.e. due to uneven surface spreading or inhomogeneous incorporation. The resulting localised hotspots of nutrient application will induce various biotic and abiotic nutrient turnover processes and fixation in the residuesphere, giving rise to distinct differences in nutrient availability, soil oxygen content and greenhouse gas (GHG) production. In this study we investigated the spatiotemporal dynamics of the reaction of manure solids and manure solids char with soil, focusing on their phosphorus (P) availability, as current emphasis on improving societal P efficiency through recycling waste or bio-based fertilisers necessitates a sound understanding of their behaviour. Soil layers amended at a constant P application rate with either pig manure solids or char made from pig manure solids were incubated for three weeks between layers of non-amended, P-depleted soil. Spatial and temporal changes in and around the amendment layers were simultaneously investigated in this study using a sandwich sensor consisting of a planar oxygen optode and multi-element diffusive gradients in thin films (DGT) gels, combined with GHG emission measurements. After three weeks of incubation, the soil containing a layer amended with manure solids had a lower overall O_2 content and had emitted significantly more CO_2 than the non-amended control or the char-amended soil. The P availability from manure solids was initially higher than that from the char, but decreased over time, whereas from the char-amended layer P availability increased in the same period. In both treatments, increases in P availability were confined to the amended soil layer and did not greatly affect P availability in the directly adjacent soil layers during the three-week incubation. These results highlight the importance of placing organic P fertilisers close to where the plant roots will grow in order to

  15. 24-Methylenecycloartanyl ferulate, a major compound of γ-oryzanol, promotes parvin-beta expression through an interaction with peroxisome proliferator-activated receptor-gamma 2 in human breast cancer cells

    International Nuclear Information System (INIS)

    Kim, Heon Woong; Lim, Eun Joung; Jang, Hwan Hee; Cui, XueLei; Kang, Da Rae; Lee, Sung Hyen; Kim, Haeng Ran; Choe, Jeong Sook; Yang, Young Mok; Kim, Jung Bong; Park, Jong Hwan

    2015-01-01

    Parvin-β is an adaptor protein that binds to integrin-linked kinase (ILK) and is significantly downregulated in breast tumors and breast cancer cell lines. We treated the breast cancer cell line MCF7 with 24-methylenecycloartanyl ferulate (24-MCF), a γ-oryzanol compound. We observed upregulation of parvin-β (GenBank Accession No. (AF237769)) and peroxisome proliferator-activated receptor (PPAR)-γ2 (GenBank Accession No. (NM-015869)). Among γ-oryzanol compounds, only treatment with 24-MCF led to the formation of reverse transcription-PCR products of parvin-β (650 and 500 bp) and PPAR-γ2 (580 bp) in MCF7 cells, but not in T47D, SK-BR-3, or MDA-MB-231 cells. 24-MCF treatment increased the mRNA and protein levels of parvin-β in MCF7 cells in a dose-dependent manner. We hypothesized that there is a correlation between parvin-β expression and induction of PPAR-γ2. This hypothesis was investigated by using a promoter-reporter assay, chromatin immunoprecipitation, and an electrophoretic mobility shift assay. 24-MCF treatment induced binding of PPAR-γ2 to a peroxisome proliferator response element-like cis-element (ACTAGGACAAAGGACA) in the parvin-β promoter in MCF7 cells in a dose-dependent manner. 24-MCF treatment significantly decreased anchorage-independent growth and inhibited cell movement in comparison to control treatment with dimethyl sulfoxide. 24-MCF treatment reduced the levels of GTP-bound Rac1 and Cdc42. Evaluation of Akt1 inhibition by 24-MCF revealed that the half maximal effective concentration was 33.3 μM. Docking evaluations revealed that 24-MCF binds to the ATP-binding site of Akt1(PDB ID: (3OCB)) and the compound binding energy is -8.870 kcal/mol. Taken together, our results indicate that 24-MCF treatment increases parvin-β expression, which may inhibit ILK downstream signaling. - Highlights: • Treatment with 24-MCF increases gene expression of parvin-β and PPAR-ϒ2 in MCF7 cells. • PPAR-ϒ2 interacts with the parvin-β gene via

  16. 24-Methylenecycloartanyl ferulate, a major compound of γ-oryzanol, promotes parvin-beta expression through an interaction with peroxisome proliferator-activated receptor-gamma 2 in human breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Heon Woong; Lim, Eun Joung; Jang, Hwan Hee [Department of Agro-Food Resources, National Academy of Agricultural Science, Rural Department Administration, Wanju-gun, Jeollabuk-do 565-851 (Korea, Republic of); Cui, XueLei [Research Institute of Medical Science, KonKuk University, School of Medicine, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701 (Korea, Republic of); Kang, Da Rae [Department of Infection & Immunology, School of Medicine, KonKuk University 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701 (Korea, Republic of); Lee, Sung Hyen; Kim, Haeng Ran; Choe, Jeong Sook [Department of Agro-Food Resources, National Academy of Agricultural Science, Rural Department Administration, Wanju-gun, Jeollabuk-do 565-851 (Korea, Republic of); Yang, Young Mok [Department of Pathology, School of Medicine and Institute of Biomedical Science and Technology, Konkuk University, Seoul 143-701 (Korea, Republic of); Kim, Jung Bong, E-mail: jungbkim@korea.kr [Department of Agro-Food Resources, National Academy of Agricultural Science, Rural Department Administration, Wanju-gun, Jeollabuk-do 565-851 (Korea, Republic of); Park, Jong Hwan, E-mail: nihpark@yahoo.com [Research Institute of Medical Science, KonKuk University, School of Medicine, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701 (Korea, Republic of)

    2015-12-25

    Parvin-β is an adaptor protein that binds to integrin-linked kinase (ILK) and is significantly downregulated in breast tumors and breast cancer cell lines. We treated the breast cancer cell line MCF7 with 24-methylenecycloartanyl ferulate (24-MCF), a γ-oryzanol compound. We observed upregulation of parvin-β (GenBank Accession No. (AF237769)) and peroxisome proliferator-activated receptor (PPAR)-γ2 (GenBank Accession No. (NM-015869)). Among γ-oryzanol compounds, only treatment with 24-MCF led to the formation of reverse transcription-PCR products of parvin-β (650 and 500 bp) and PPAR-γ2 (580 bp) in MCF7 cells, but not in T47D, SK-BR-3, or MDA-MB-231 cells. 24-MCF treatment increased the mRNA and protein levels of parvin-β in MCF7 cells in a dose-dependent manner. We hypothesized that there is a correlation between parvin-β expression and induction of PPAR-γ2. This hypothesis was investigated by using a promoter-reporter assay, chromatin immunoprecipitation, and an electrophoretic mobility shift assay. 24-MCF treatment induced binding of PPAR-γ2 to a peroxisome proliferator response element-like cis-element (ACTAGGACAAAGGACA) in the parvin-β promoter in MCF7 cells in a dose-dependent manner. 24-MCF treatment significantly decreased anchorage-independent growth and inhibited cell movement in comparison to control treatment with dimethyl sulfoxide. 24-MCF treatment reduced the levels of GTP-bound Rac1 and Cdc42. Evaluation of Akt1 inhibition by 24-MCF revealed that the half maximal effective concentration was 33.3 μM. Docking evaluations revealed that 24-MCF binds to the ATP-binding site of Akt1(PDB ID: (3OCB)) and the compound binding energy is -8.870 kcal/mol. Taken together, our results indicate that 24-MCF treatment increases parvin-β expression, which may inhibit ILK downstream signaling. - Highlights: • Treatment with 24-MCF increases gene expression of parvin-β and PPAR-ϒ2 in MCF7 cells. • PPAR-ϒ2 interacts with the parvin-β gene via

  17. Comprehensive profiling and localisation of the matrix metalloproteinases in urothelial carcinoma

    OpenAIRE

    Wallard, M J; Pennington, C J; Veerakumarasivam, A; Burtt, G; Mills, I G; Warren, A; Leung, H Y; Murphy, G; Edwards, D R; Neal, D E; Kelly, J D

    2006-01-01

    The matrix metalloproteinases (MMPs) are endopeptidases which break down the extracellular matrix and regulate cytokine and growth factor activity. Several MMPs have been implicated in the promotion of invasion and metastasis in a broad range of tumours including urothelial carcinoma. In this study, RNA from 132 normal bladder and urothelial carcinoma specimens was profiled for each of the 24 human MMPs, the four endogenous tissue inhibitors of MMPs (TIMPs) and several key growth factors and ...

  18. ROLE OF CT IN LOCALISING THE INJURY TO THE PARTICULAR INTRACRANIAL COMPARTMENT IN PATIENTS WITH CRANIOCEREBRAL TRAUMA

    Directory of Open Access Journals (Sweden)

    Bonthu Anuradh

    2016-11-01

    Full Text Available BACKGROUND To evaluate and asses the role of CT in localising the injury to the particular intracranial compartment in patients with craniocerebral trauma. To evaluate the value of early CT imaging, which helps in patient prognosis. To correlate CT findings with Glasgow coma scale and clinical findings there by guide the neurosurgeon for the surgical planning. MATERIALS AND METHODS The study was conducted at Department of Radiology, Government General Hospital, Kakinada, from September 2012 to September 2014 over a period of two years. The study includes evaluation of 300 cases of craniocerebral trauma. All age groups were included. RESULTS A higher incidence noted in males and age group of 20-29 years and moderate Glasgow coma scale in majority of cases. Most common presenting symptom being loss of consciousness followed by vomiting. The commonest finding on CT being subdural haematoma followed by intraparenchymal haematoma. Skull fractures noted in 74% of cases. All the patients with moderate Glasgow coma scale showed intracranial bleeds. Out of 300 patients, normal CT findings in 159 patients that is 53% and abnormal CT findings in 141 patients that is 47%. CONCLUSION Incidence of road traffic accidents was more in male population with peak age incidence in between 20-30 years. Subdural haematoma was most common form of intracerebral bleed. Glasgow coma scale combined with relevant presenting complaints can be used as an indication for CT scan in order to avoid unnecessary CT scans.

  19. Organ and Tissue-Specific Localisation of Selected Cell Wall Epitopes in the Zygotic Embryo of Brachypodium distachyon

    Directory of Open Access Journals (Sweden)

    Alexander Betekhtin

    2018-03-01

    Full Text Available The plant cell wall shows a great diversity regarding its chemical composition, which may vary significantly even during different developmental stages. In this study, we analysed the distribution of several cell wall epitopes in embryos of Brachypodium distachyon (Brachypodium. We also described the variations in the nucleus shape and the number of nucleoli that occurred in some embryo cells. The use of transmission electron microscopy, and histological and immunolocalisation techniques permitted the distribution of selected arabinogalactan proteins, extensins, pectins, and hemicelluloses on the embryo surface, internal cell compartments, and in the context of the cell wall ultrastructure to be demonstrated. We revealed that the majority of arabinogalactan proteins and extensins were distributed on the cell surface and that pectins were the main component of the seed coat and other parts, such as the mesocotyl cell walls and the radicula. Hemicelluloses were localised in the cell wall and outside of the radicula protodermis, respectively. The specific arrangement of those components may indicate their significance during embryo development and seed germination, thus suggesting the importance of their protective functions. Despite the differences in the cell wall composition, we found that some of the antibodies can be used as markers to identify specific cells and the parts of the developing Brachypodium embryo.

  20. 3D printed facial laser scans for the production of localised radiotherapy treatment masks - A case study.

    Science.gov (United States)

    Briggs, Matthew; Clements, Helen; Wynne, Neil; Rennie, Allan; Kellett, Darren

    This study investigates the use of 3D printing for patients that require localised radiotherapy treatment to the face. The current process involves producing a lead mask in order to protect the healthy tissue from the effects of the radiotherapy. The mask is produced by applying a thermoplastic sheet to the patient's face and allowing to set hard. This can then be used as a mould to create a plaster impression of the patient's face. A sheet of lead is then hammered on to the plaster to create a bespoke fitted face mask. This process can be distressing for patients and can be problematic when the patient is required to remain motionless for a prolonged time while the thermoplastic sets. In this study, a 1:1 scale 3D print of a patient's face was generated using a laser scanner. The lead was hammered directly on to the surface of the 3D print in order to create a bespoke fitted treatment mask. This eliminated the thermoplastic moulding stage and significantly reduced the time needed for the patient to be in clinic. The higher definition impression of the the face resulted in a more accurate, better fitting treatment mask.

  1. A prospective analysis of long-term quality of life after permanent I-125 brachytherapy for localised prostate cancer

    International Nuclear Information System (INIS)

    Ash, Dan; Bottomley, David; Al-Qaisieh, Bashar; Carey, Brendan; Gould, Kath; Henry, Ann

    2007-01-01

    Background and purpose: To prospectively evaluate long-term urinary, bowel and sexual function after I-125 brachytherapy for localised prostate cancer using patient administered validated Quality of Life (QoL) instruments. Materials and methods: Between March 1995 and March 2004, 673 men underwent brachytherapy and recorded urinary symptoms prospectively using the International Prostate Symptom Score (IPSS). In addition, in a subgroup of 116 patients, the Expanded Prostate Cancer Index Composite (EPIC) was used to record QoL information on urinary, bowel and sexual function before treatment and at regular time intervals for at least two years. Results: Initially, there was a sharp rise in urinary symptoms which was most marked within the first three months. Scores then resolved slowly and returned to within one or two units of pre-treatment level at one year. Subsequently, there was no significant deterioration in urinary symptoms up to nine years following brachytherapy. Few had significant bowel symptoms. Sexual function deteriorated initially and then improved but failed to return to pre-treatment levels by two years. Patients requiring neo-adjuvant hormones experienced significantly more dysfunction. Conclusions: After an initial period of mild to moderate urinary symptoms prostate brachytherapy is well tolerated with relatively little deterioration in long-term quality of life. Long-term reduction in sexual function may be seen particularly in those requiring hormones

  2. Charge carrier localised in zero-dimensional (CH3NH3)3Bi2I9 clusters.

    Science.gov (United States)

    Ni, Chengsheng; Hedley, Gordon; Payne, Julia; Svrcek, Vladimir; McDonald, Calum; Jagadamma, Lethy Krishnan; Edwards, Paul; Martin, Robert; Jain, Gunisha; Carolan, Darragh; Mariotti, Davide; Maguire, Paul; Samuel, Ifor; Irvine, John

    2017-08-01

    A metal-organic hybrid perovskite (CH 3 NH 3 PbI 3 ) with three-dimensional framework of metal-halide octahedra has been reported as a low-cost, solution-processable absorber for a thin-film solar cell with a power-conversion efficiency over 20%. Low-dimensional layered perovskites with metal halide slabs separated by the insulating organic layers are reported to show higher stability, but the efficiencies of the solar cells are limited by the confinement of excitons. In order to explore the confinement and transport of excitons in zero-dimensional metal-organic hybrid materials, a highly orientated film of (CH 3 NH 3 ) 3 Bi 2 I 9 with nanometre-sized core clusters of Bi 2 I 9 3- surrounded by insulating CH 3 NH 3 + was prepared via solution processing. The (CH 3 NH 3 ) 3 Bi 2 I 9 film shows highly anisotropic photoluminescence emission and excitation due to the large proportion of localised excitons coupled with delocalised excitons from intercluster energy transfer. The abrupt increase in photoluminescence quantum yield at excitation energy above twice band gap could indicate a quantum cutting due to the low dimensionality.Understanding the confinement and transport of excitons in low dimensional systems will aid the development of next generation photovoltaics. Via photophysical studies Ni et al. observe 'quantum cutting' in 0D metal-organic hybrid materials based on methylammonium bismuth halide (CH 3 NH 3 )3Bi 2 I 9 .

  3. Reproduction and mode of delivery in women with vaginismus or localised provoked vestibulodynia: a Swedish register-based study.

    Science.gov (United States)

    Möller, L; Josefsson, A; Bladh, M; Lilliecreutz, C; Sydsjö, G

    2015-02-01

    To compare sociodemographics, parity and mode of delivery between women diagnosed with vaginismus or localised provoked vestibulodynia (LPV) to women without a diagnosis before first pregnancy. Retrospective, population-based register study. Sweden. All women born in Sweden 1973-83 who gave birth for the first time or remained nulliparous during the years 2001-09. Nationally linked registries were used to identify the study population. Women diagnosed with vaginismus or LPV were compared to all other women. Odds ratios for parity and mode of delivery were calculated using multinominal regression analysis and logistic regression. Parity and mode of delivery. Women with vaginismus/LPV were more likely to be unmarried (P = 0.001), unemployed (P = 0.012), have a higher educational level (P vaginismus/LPV more often delivered by caesarean section (P vaginismus/LPV were more likely to suffer a perineal laceration (adjusted OR 1.87, 95% CI 1.56-2.25). Women with vaginismus/LPV are less likely to give birth and those that do are more likely to deliver by caesarean section and have a caesarean section based upon maternal request. Those women delivering vaginally are more likely to suffer perineal laceration. These findings point to the importance of not only addressing sexual function in women with vaginismus/LPV but reproductive function as well. © 2014 Royal College of Obstetricians and Gynaecologists.

  4. Localising the nitrogen imprint of the Paris food supply: the potential of organic farming and changes in human diet

    Science.gov (United States)

    Billen, G.; Garnier, J.; Thieu, V.; Silvestre, M.; Barles, S.; Chatzimpiros, P.

    2012-01-01

    The Seine watershed has long been the food-supplying hinterland of Paris, providing most of the animal and vegetal protein consumed in the city. Nowadays, the shift from manure-based to synthetic nitrogen fertilisation, has made possible a strong land specialisation of agriculture in the Seine watershed: it still provides most of the cereal consumed by the Paris agglomeration, but exports 80% of its huge cereal production. On the other hand the meat and milk supply originates mainly from regions in the North and West of France, specialised in animal farming and importing about 30% of their feed from South America. As it works today, this system is responsible for a severe nitrate contamination of surface and groundwater resources. Herein two scenarios of re-localising Paris's food supply are explored, based on organic farming and local provision of animal feed. We show that for the Seine watershed it is technically possible to design an agricultural system able to provide all the plant- and animal-based food required by the population, to deliver sub-root water meeting the drinking water standards and still to export a significant proportion of its production to areas less suitable for cereal cultivation. Decreasing the share of animal products in the human diet has a strong impact on the nitrogen imprint of urban food supply.

  5. Isotope effect in monolayer, localised, immobilised adsorption with special reference to neon adsorption on porous glass at cryogenic temperatures

    International Nuclear Information System (INIS)

    Srisaila, S.; Bajpai, M.B.

    1980-01-01

    Using statistical mechanics, a general formula for the separation factor of two isotopes between gas and adsorbate phases in a monolayer, localised, immobile adsorption on a heterogeneous surface, is derived. Special forms of this are discussed for which the familiar Bigeleisen form is one. Purer, Kalplan and Smith, in their work on neon isotopes separation by gas chromatography through porous glass column at cryogenic temperatures, have reported that the separation factor first increased and then decreased as the temperature was decreased, whereas monotonic increase was the normally expected behaviour. Moiseyev has attempted to explain the anomaly after assuming two types of adsorption sites. The present theory gives the conditions in which monotonic and nonmonotonic variations can occur and after making some assumptions, the experimental curve of Purer et al could be reproduced computationally using one form of the general expression. This theoretical treatment highlights the importance of both potential energy and force constant in isotope effect whereas it is only the potential energy that is much involved in most adsorption studies. (auth.)

  6. Globalised Markets and Localised Needs. Relocating Design Competence in a New Industrial Context

    DEFF Research Database (Denmark)

    Morelli, Nicola

    2006-01-01

    Globalisation implies several phenomena, such as the expansion of markets and the relocation of production. However the success of global production is linked to business companies’ capability to generate local and individualized solutions. In order to put together global production and local...... solutions, industries have to develop a new capability to mobilize local networks of actors and enable final customers to play an active role in the production of the final solution. This implies a radical change in the social role of business companies and, from the designer’s perspective, a genetic change...

  7. Systematic Characterisation of Cellular Localisation and Expression Profiles of Proteins Containing MHC Ligands

    DEFF Research Database (Denmark)

    Juncker, Agnieszka; Larsen, Mette Voldby; Weinhold, Nils

    2009-01-01

    Background: Presentation of peptides on Major Histocompatibility Complex (MHC) molecules is the cornerstone in immune system activation and increased knowledge of the characteristics of MHC ligands and their source proteins is highly desirable. Methodology/Principal Finding: In the present large......-scale study, we used a large data set of proteins containing experimentally identified MHC class I or II ligands and examined the proteins according to their expression profiles at the mRNA level and their Gene Ontology (GO) classification within the cellular component ontology. Proteins encoded by highly...

  8. [Clinical epidemiological assessments on 3521 patients suffering from road traffic injuries, in relation with trauma localisation and severity, assisted in "Sf. Ioan" Emergency Unit, during 2002-2009].

    Science.gov (United States)

    Manole, M; Ciuhodaru, T; Zanoschi, Georgeta; Manole, Alina; Ivan, A

    2011-01-01

    The aim of study was to assess road traffic injuries in relation with their localisation and severity. A sample of 3521 patients suffering from road traffic injuries and assisted in "Sf. Ioan" Emergency Unit, Iaşi, Romania was assess regarding age group, sex and residence area, type of lesions and ther localisation and severity, between 2002-2009. Data were collected using a special epidemiological inquiry and processed using SPSS and MS Excel statistical softs. The incidence of road traffic injuries increased during the last decade, with a report men/women of 1.5, urban and 21-30 age group predominance. The most frequent were leg fractures (16.7%) and thoracal contusions (19.1%), cranial and facial trauma (32.4%), with open injuries (10.5%). Prevention programmes with a high efficiency at the national level, as well as a concret identification of risk factors with a multidisciplinar approach of road traffic accidents, are needed.

  9. Detection of localised corrosion by means of statistic and harmonic analysis of spontaneous potential noise

    International Nuclear Information System (INIS)

    Carassiti, F.; Cigna, R.; Goolamallee, R.; Gusmano, G.

    1989-01-01

    The analysis of the electrochemical noise, i.e. of the spontaneous fluctuations of potential of a freely corroding electrode, probably represent one of the most interesting novelty of the last years in the field of corrosion monitoring. Although this technique is still at an early stage, it could lead to interesting developments, especially for identifying localized forms of corrosion. The experiments which have been reported in the literature generally agree that in absence of active corrosion a slight variation of the potential is observed accompanied by non gaussian fluctuations; in presence of the onset of pitting a series of sharp variation is observed followed by relatively slow exponential recovery. In the domain of frequency the slope of the noise frequency curve is less than that noticed in the absence of active corrosion. In the domain of time generally the standard deviation of noise is proportional to the corrosion rate. Moreover it has been noticed that small variation in the experimental condition could cause modification in the shape of the spontaneous potential fluctuation and introduce some confusion in the analysis of data. Digital filtering of disturbs could allow a better reproducibility to be achieved. (author) 4 refs., 9 figs

  10. A core outcome set for localised prostate cancer effectiveness trials: protocol for a systematic review of the literature and stakeholder involvement through interviews and a Delphi survey.

    Science.gov (United States)

    MacLennan, Steven; Bekema, Hendrika J; Williamson, Paula R; Campbell, Marion K; Stewart, Fiona; MacLennan, Sara J; N'Dow, James M O; Lam, Thomas B L

    2015-03-04

    Prostate cancer is a growing health problem worldwide. The management of localised prostate cancer is controversial. It is unclear which of several surgical, radiotherapeutic, ablative, and surveillance treatments is the most effective. All have cost, process and recovery, and morbidity implications which add to treatment decision-making complexity for patients and healthcare professionals. Evidence from randomised controlled trials (RCTs) is not optimal because of uncertainty as to what constitutes important outcomes. Another issue hampering evidence synthesis is heterogeneity of outcome definition, measurement, and reporting. This project aims to determine which outcomes are the most important to patients and healthcare professionals, and use these findings to recommend a standardised core outcome set for comparative effectiveness trials of treatments for localised prostate cancer, to optimise decision-making. The range of potentially important outcomes and measures will be identified through systematic reviews of the literature and semi-structured interviews with patients. A consultation exercise involving representatives from two key stakeholder groups (patients and healthcare professionals) will ratify the list of outcomes to be entered into a three round Delphi study. The Delphi process will refine and prioritise the list of identified outcomes. A methodological substudy (nested RCT design) will also be undertaken. Participants will be randomised after round one of the Delphi study to one of three feedback groups, based on different feedback strategies, in order to explore the potential impact of feedback strategies on participant responses. This may assist the design of a future core outcome set and Delphi studies. Following the Delphi study, a final consensus meeting attended by representatives from both stakeholder groups will determine the final recommended core outcome set. This study will inform clinical practice and future trials of interventions of

  11. A Multi-Phase Methodology for Investigating Localisation Policies within the GCC: The Hotel Industry in the KSA and the UAE

    OpenAIRE

    Areej Azhar; Peter Duncan; David Edgar

    2014-01-01

    Due to a high unemployment rate among local people and a high reliance on expatriate workers, the governments in the Gulf Co-operation Council (GCC) countries have been implementing programmes of localisation (replacing foreign workers with GCC nationals). These programmes have been successful in the public sector but much less so in the private sector. However, there are now insufficient jobs for locals in the public sector and the onus to provide employment has fallen o...

  12. Comparison of 68Ga-DOTANOC PET/CT and contrast-enhanced CT in localisation of tumours in ectopic ACTH syndrome

    Science.gov (United States)

    Jadhav, Swati S; Lila, Anurag R; Kasaliwal, Rajeev; Khare, Shruti; Yerawar, Chaitanya G; Hira, Priya; Phadke, Uday; Shah, Hina; Lele, Vikram R; Malhotra, Gaurav; Bandgar, Tushar; Shah, Nalini S

    2016-01-01

    Background Localising ectopic adrenocorticotrophic hormone (ACTH) syndrome (EAS) tumour source is challenging. Somatostatin receptor-based PET imaging has shown promising results, but the data is limited to case reports and small case series. We reviewed here the performance of 68Ga-DOTANOC positron emission tomography (PET)/computed tomography (CT) and contrast-enhanced CT (CECT) in our cohort of 12 consecutive EAS patients. Materials and methods Retrospective data analysis of 12 consecutive patients of EAS presenting to a single tertiary care centre in a period between January 2013 and December 2014 was done. CECT and 68Ga-DOTANOC PET/CT were reported (blinded) by an experienced radiologist and a nuclear medicine physician, respectively. The performance of CECT and 68Ga-DOTANOC PET/CT was compared. Results Tumours could be localised in 11 out of 12 patients at initial presentation (overt cases), whereas in one patient, tumour remained occult. Thirteen lesions were identified in 11 patients as EAS source (true positives). CECT localised 12 out of these 13 lesions (sensitivity 92.3%) and identified five false-positive lesions (positive predictive value (PPV) 70.5%). Compared with false-positive lesions, true-positive lesions had greater mean contrast enhancement at 60s (33.2 vs 5.6 Hounsfield units (HU)). 68Ga-DOTANOC PET/CT was able to identify 9 out of 13 lesions (sensitivity 69.2%) and reported no false-positive lesions (PPV 100%). Conclusion CECT remains the first-line investigation in localisation of EAS. The contrast enhancement pattern on CECT can further aid in characterisation of the lesions. 68Ga-DOTANOC PET/CT can be added to CECT, to enhance positive prediction of the suggestive lesions. PMID:27006371

  13. The role of localised Ultra-Low Frequency waves in energetic electron precipitation

    Science.gov (United States)

    Rae, J.; Murphy, K. R.; Watt, C.; Mann, I. R.; Ozeke, L.; Halford, A. J.; Sibeck, D. G.; Clilverd, M. A.; Rodger, C. J.; Degeling, A. W.; Singer, H. J.

    2016-12-01

    Electromagnetic waves play pivotal roles in radiation belt dynamics through a variety of different means. Typically, Ultra-Low Frequency (ULF) waves have historically been invoked for radial diffusive transport leading to both acceleration and loss of outer radiation belt electrons. Very-Low Frequency (VLF) and Extremely-Low Frequency (ELF) waves are generally thought to provide a mechanism for localized acceleration and loss through precipitation into the ionosphere. In this study we present a new mechanism for electron loss through precipitation into the ionosphere due to direct modulation of the loss cone via localized compressional ULF waves. Observational evidence is presented demonstrating that modulation of the equatorial loss cone can occur via localized compressional wave activity. We then perform statistical computations of the probability distribution to determine how likely a given magnetic perturbation would produce a given percentage change in the bounce loss-cone (BLC). We discuss the ramifications of the action of coherent, localized compressional ULF waves on drifting electron populations; their precipitation response can be a complex interplay between electron energy, the shape of the phase space density profile at pitch angles close to the loss cone, ionospheric decay timescales, and the time-dependence of the electron source. We present a case study of compressional wave activity in tandem with riometer and balloon-borne electron precipitation across keV-MeV energies to demonstrate that the experimental measurements can be explained by our new enhanced loss cone mechanism. We determine that the two pivotal components not usually considered are localized ULF wave fields and ionospheric decay timescales. We conclude that ULF wave modulation of the loss cone is a viable candidate for direct precipitation of radiation belt electrons without any additional requirement for gyroresonant wave-particle interaction. Additional mechanisms would be

  14. Effect of coulomb interaction on Anderson localization; Effet de l'interaction coulombienne sur la localisation d'Anderson dans des systemes de basses dimensions

    Energy Technology Data Exchange (ETDEWEB)

    Waintal, X

    1999-09-10

    We study the quantum mechanics of interacting particles in a disordered system, and in particular, what happens to Anderson localisation when interaction is taken into account. In the first part,one looks at the excited states of two particles in one dimension. For this model, it has been shown (Shepelyansky 1994) that a local repulsive interaction can partially destroy Anderson localisation. Here, we show that this model has similarities with the three-dimensional Anderson model at the metal-insulator transition. In particular, the maximum of rigidity obtained in the spectral statistics correspond to some intermediary statistics that cannot be described by random matrix theory neither by a Poisson statistics. The wave functions show a multifractal behaviour and the spreading of the center of mass of a wave packet is logarithmic in time. The second part deals with the ground state of a finite density of spinless fermions in two dimensions. After the scaling theory of localisation, it was commonly accepted that there was no metal in two dimensions. This idea has been challenged by the observation of a metal-insulator transition in low density electron gas (Kravchenko et al. 1994). We propose a scenario in which a metallic phase occurs between the Anderson insulator and the pinned Wigner crystal. This intermediate phase is characterized by an alignment of the local currents flowing in the system. (author)

  15. Spatio-temporal manipulation of small GTPase activity at subcellular level and on timescale of seconds in living cells.

    Science.gov (United States)

    DeRose, Robert; Pohlmeyer, Christopher; Umeda, Nobuhiro; Ueno, Tasuku; Nagano, Tetsuo; Kuo, Scot; Inoue, Takanari

    2012-03-09

    Dynamic regulation of the Rho family of small guanosine triphosphatases (GTPases) with great spatiotemporal precision is essential for various cellular functions and events(1, 2). Their spatiotemporally dynamic nature has been revealed by visualization of their activity and localization in real time(3). In order to gain deeper understanding of their roles in diverse cellular functions at the molecular level, the next step should be perturbation of protein activities at a precise subcellular location and timing. To achieve this goal, we have developed a method for light-induced, spatio-temporally controlled activation of small GTPases by combining two techniques: (1) rapamycin-induced FKBP-FRB heterodimerization and (2) a photo-caging method of rapamycin. With the use of rapamycin-mediated FKBP-FRB heterodimerization, we have developed a method for rapidly inducible activation or inactivation of small GTPases including Rac(4), Cdc42(4), RhoA(4) and Ras(5), in which rapamycin induces translocation of FKBP-fused GTPases, or their activators, to the plasma membrane where FRB is anchored. For coupling with this heterodimerization system, we have also developed a photo-caging system of rapamycin analogs. A photo-caged compound is a small molecule whose activity is suppressed with a photocleavable protecting group known as a caging group. To suppress heterodimerization activity completely, we designed a caged rapamycin that is tethered to a macromolecule such that the resulting large complex cannot cross the plasma membrane, leading to virtually no background activity as a chemical dimerizer inside cells(6). Figure 1 illustrates a scheme of our system. With the combination of these two systems, we locally recruited a Rac activator to the plasma membrane on a timescale of seconds and achieved light-induced Rac