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Search Results: 1 - 10 of 138738 matches for " K. Mikenberg "
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GABA Withdrawal Modifies Network Activity in Cultured Hippocampal Neurons
H. Golan,K. Mikenberg,V. Greenberger,M. Segal
Neural Plasticity , 2000, DOI: 10.1155/np.2000.31
Abstract: Dissociated hippocampal neurons, grown in culture for 2 to 3 weeks, tended to fire bursts of synaptic currents at fairly regular intervals, representing network activity. A brief exposure of cultured neurons to GABA caused a total suppression of the spontaneous network activity. Following a washout of GABA, the activity was no longer clustered in bursts and instead, the cells fired at a high rate tonic manner. The effect of removing GABA could be seen as long as 1 to 2 days after GABA withdrawal and is expressed as an increase in the number of active cells in a network, as well as in their firing rates. Such striking effects of GABA removal may underlie part of the GABA withdrawal syndrome seen elsewhere.
Transcription Factor NF-κB Is Transported to the Nucleus via Cytoplasmic Dynein/Dynactin Motor Complex in Hippocampal Neurons
Ilja Mikenberg, Darius Widera, Aljoscha Kaus, Barbara Kaltschmidt, Christian Kaltschmidt
PLOS ONE , 2007, DOI: 10.1371/journal.pone.0000589
Abstract: Background Long-term changes in synaptic plasticity require gene transcription, indicating that signals generated at the synapse must be transported to the nucleus. Synaptic activation of hippocampal neurons is known to trigger retrograde transport of transcription factor NF-κB. Transcription factors of the NF-κB family are widely expressed in the nervous system and regulate expression of several genes involved in neuroplasticity, cell survival, learning and memory. Principal Findings In this study, we examine the role of the dynein/dynactin motor complex in the cellular mechanism targeting and transporting activated NF-κB to the nucleus in response to synaptic stimulation. We demonstrate that overexpression of dynamitin, which is known to dissociate dynein from microtubules, and treatment with microtubule-disrupting drugs inhibits nuclear accumulation of NF-κB p65 and reduces NF-κB-dependent transcription activity. In this line, we show that p65 is associated with components of the dynein/dynactin complex in vivo and in vitro and that the nuclear localization sequence (NLS) within NF-κB p65 is essential for this binding. Conclusion This study shows the molecular mechanism for the retrograde transport of activated NF-κB from distant synaptic sites towards the nucleus.
Tumor necrosis factor α triggers proliferation of adult neural stem cells via IKK/NF-κB signaling
Darius Widera, Ilja Mikenberg, Margitta Elvers, Christian Kaltschmidt, Barbara Kaltschmidt
BMC Neuroscience , 2006, DOI: 10.1186/1471-2202-7-64
Abstract: Here we describe for the first time the TNF-mediated signal transduction cascade in neural stem cells (NSCs) that results in increased proliferation. Moreover, we demonstrate IKK-α/β-dependent proliferation and markedly up-regulated cyclin D1 expression after TNF treatment. The significant increase in proliferation in TNF-treated cells was indicated by increased neurosphere volume, increased bromodeoxyuridin (BrdU) incorporation and a higher total cell number. Furthermore, TNF strongly activated nuclear factor-kappa B (NF-κB) as measured by reporter gene assays and by an activity-specific antibody. Proliferation of control and TNF-treated NSCs was strongly inhibited by expression of the NF-κB super-repressor IκB-AA1. Pharmacological blockade of IκB ubiquitin ligase activity led to comparable decreases in NF-κB activity and proliferation. In addition, IKK-β gene product knock-down via siRNA led to diminished NF-κB activity, attenuated cyclin D1 expression and finally decreased proliferation. In contrast, TGFβ-activated kinase 1 (TAK-1) is partially dispensable for TNF-mediated and endogenous proliferation. Understanding stem cell proliferation is crucial for future regenerative and anti-tumor medicine.TNF-mediated activation of IKK-β resulted in activation of NF-κB and was followed by up-regulation of the bona-fide target gene cyclin D1. Activation of the canonical NF-κB pathway resulted in strongly increased proliferation of NSCs.During mammalian central nervous system (CNS) development, multipotent precursor cells (stem cells) undergo division, cell fate specification, and maturation in response to extrinsic cues. These neural stem cells are characterized by the ability to undergo cell division and to differentiate into multiple cell types, e.g. neurons or glial cells.There are two major sources of adult neural stem cells within the adult brain: the subgranular zone of the hippocampus and the subventricular zone (SVZ) [1,2]. SVZ-derived NSCs can be cultured as self
Tumor necrosis factor alpha induced proliferation of adult neural stem cells is mediated via NF-κB
Widera Darius,Mikenberg Ilja,Elvers Margitta,Kaltschmidt Christian
BMC Neuroscience , 2007, DOI: 10.1186/1471-2202-8-s1-p1
Nuclear Factor-kappaB controls the reaggregation of 3D neurosphere cultures in vitro
D Widera,I Mikenberg,A Kaus,C Kaltschmidt
European Cells and Materials (ECM) , 2006,
Abstract: The approach of reaggregation involves the regeneration and self-renewal of histotypical 3D spheres from isolated tissue kept in suspension culture. Reaggregated spheres can be used as tumour, genetic, biohybrid and neurosphere models. In addition the functional superiority of 3D aggregates over conventional 2D cultures developed the use of neurospheres for brain engineering of CNS diseases. Thus 3D aggregate cultures created enormous interest in mechanisms that regulate the formation of multicellular aggregates in vitro. Here we analyzed mechanisms guiding the development of 3D neurosphere cultures. Adult neural stem cells can be cultured as self-adherent clusters, called neurospheres. Neurospheres are characterised as heterogeneous clusters containing unequal stem cell sub-types. Tumour necrosis factor-alpha (TNF- alpha is one of the crucial inflammatory cytokines with multiple actions on several cell types. TNF- alpha strongly activates the canonical Nuclear Factor Kappa-B (NF-kappaB) pathway. In order to investigate further functions of TNF in neural stem cells (NSCs) we tested the hypothesis that TNF is able to modulate the motility and/or migratory behaviour of SVZ derived adult neural stem cells. We observed a significantly faster sphere formation in TNF treated cultures than in untreated controls. The very fast aggregation of isolated NSCs (<2h) is a commonly observed phenomenon, though the mechanisms of 3D neurosphere formation remain largely unclear. Here we demonstrate for the first time, increased aggregation and enhanced motility of isolated NSCs in response to the TNF-stimulus. Moreover, this phenomenon is largely dependent on activated transcription factor NF-kappaB. Both, the pharmacological blockade of NF-kappaB pathway by pyrrolidine dithiocarbamate (PDTC) or Bay11-7082 and genetic blockade by expression of a transdominant-negative super-repressor IkappaB-AA1 led to decreased aggregation.
The use of cluster quality for track fitting in the CSC detector
Erez Etzion,David Primor,Giora Mikenberg,Nir Amram,Hagit Messer
Physics , 2006,
Abstract: The new particle accelerators and its experiments create a challenging data processing environment, characterized by large amount of data where only small portion of it carry the expected new scientific information. Modern detectors, such as the Cathode Strip Chamber (CSC), achieve high accuracy of coordinate measurements (between 50 to 70 microns). However, heavy physical backgrounds can decrease the accuracy significantly. In the presence of such background, the charge induced over adjacent CSC strips (cluster) is different from the ideal Matheison distribution. The traditional least squares method which takes the same ideal position error for all clusters loses its optimal properties on contaminated data. A new technique that calculates the cluster quality and uses it to improve the track fitting results is suggested. The algorithm is applied on test beam data, and its performance is compared to other fitting methods. It is shown that the suggested algorithm improves the fitting performance significantly.
The Certification of ATLAS Thin Gap Chambers Produced in Israel and China
E. Etzion,Y. Benhammou,J. Ginzburg,M. Ishino,L. Levinson,G. Mikenberg,N. Panikashvili,D. Primor,Y. Rozen,V. Smakhtin,S. Tarem
Physics , 2004,
Abstract: Thin gap chambers (TGCs) are used for the muon trigger system in the forward region of the LHC experiment ATLAS. A TGC consists of a plane of closely spaced wires maintained at positive high voltage, sandwiched between resistive grounded cathode planes with an anode wire to cathode plane gap distance smaller than the wire-to-wire spacing. The TGCs are expected to provide a trigger signal within 25 ns of the bunch spacing of the LHC accelerator, with an efficiency exceeding 95%, while exposed to an effective photon and neutron background ranging from 30 to 500 Hz/cm2. About 2,500 out of the 3,600 ATLAS TGCs are being produced at the Weizmann institute in Israel, and in Shandong University in China. Once installed in the ATLAS detector the TGCs will be inaccessible. A vigorous production quality control program is therefore implemented at the production sites. Furthermore, after chamber completion, a thorough program of quality assurance is implemented to ensure the efficient performance of the chambers during more than ten years of operation in the LHC high rate environment. This program consists of a detailed mapping of the detectors response using cosmic rays, as well as checking the chambers behavior using a high rate radiation source. An aging test performed on five chambers in a serial gas connection is presented. Finally the results of the chambers certification tests performed at CERN before the installation in ATLAS are described.
Position resolution and efficiency measurements with large scale Thin Gap Chambers for the super LHC
Nir Amram,Gideon Bella,Yan Benhammou,Marco A. Diaz,Ehud Duchovni,Erez Etzion,Alon Hershenhorn,Amit Klier,Nachman Lupu,Giora Mikenberg,Dmitry Milstein,Yonathan Munwes,Osamu Sasaki,Meir Shoa,Vladimir Smakhtin,Ulrich Volkmann
Physics , 2010, DOI: 10.1016/j.nima.2010.06.311
Abstract: New developments in Thin Gap Chambers (TGC) detectors to provide fast trigger and high precision muon tracking under sLHC conditions are presented. The modified detectors are shown to stand a high total irradiation dose equivalent to 6 Coulomb/cm of wire, without showing any deterioration in their performance. Two large (1.2 x 0.8 m^2) prototypes containing four gaps, each gap providing pad, strips and wires readout, with a total thickness of 50 mm, have been constructed. Their local spatial resolution has been measured in a 100 GeV/c muon test beam at CERN. At perpendicular incidence angle, single gap position resolution better than 60 microns has been obtained. For incidence angle of 20 degrees resolution of less than 100 micron was achieved. TGC prototypes were also tested under a flux of 10^5 Hz/cm^2 of 5.5-6.5 MeV neutrons, showing a high efficiency for cosmic muons detection.
Higgs Physics at LEP2
M. Carena,P. Zerwas,E. Accomando,P. Bagnaia,A. Ballestrero,P. Bambade,D. Bardin,F. Berends,J. van der Bij,T. Binoth,G. Burkart,F. de Campos,R. Contri,G. Crosetti,J. Cuevas Maestro,A. Dabelstein,W. de Boer,C. de StJean,F. Di Lodovico,A. Djouadi,V. Driesen,M. Dubinin,E. Duchovni,O. J. P. Eboli,R. Ehret,U. Ellwanger,J. -P. Ernenwein,J. -R. Espinosa,R. Faccini,M. Felcini,R. Folman,H. Genten,J. -F. Grivaz,E. Gross,J. Guy,H. Haber,Cs. Hajdu,S. W. Ham,R. Hempfling,A. Hoang,W. Hollik,S. Hoorelbeke,K. Hultqvist,P. Igo-Kemenes,P. Janot,S. de Jong,U. Jost,J. Kalinowski,S. Katsanevas,R. Ker?nen,W. Kilian,B. R. Kim,S. F. King,R. Kleiss,B. A. Kniehl,M. Kr?mer,A. Leike,E. Lund,V. Lund,P. Lutz,J. Marco,C. Mariotti,J. -P. Martin,C. Martinez-Rivero,G. Mikenberg,M. R. Monge,G. Montagna,O. Nicrosini,S. K. Oh,P. Ohmann,G. Passarino,F. Piccinini,R. Pittau,T. Plehn,M. Quiros,M. Rausch de Traubenberg,T. Riemann,J. Rosiek,V. Ruhlmann-Kleider,C. A. Savoy,P. Sherwood,S. Shichanin,R. Silvestre,A. Sopczak,M. Spira,J. W. F. Valle,D. Vilanova,C. E. M. Wagner,P. L. White,T. Wlodek,G. Wolf,S. Yamashita,F. Zwirner
Physics , 1996,
Abstract: In this report we review the prospects for Higgs physics at LEP2. The theoretical aspects and the phenomenology of Higgs particles are discussed within the Standard Model (SM) and the Minimal Supersymmetric Standard Model (MSSM). The experimental search techniques are described and the discovery limits for Higgs bosons in the LEP2 energy range are summarized. In addition, opportunities of detecting Higgs particles in non-minimal extensions of the SM and the MSSM are investigated.
Performance of a Full-Size Small-Strip Thin Gap Chamber Prototype for the ATLAS New Small Wheel Muon Upgrade
Angel Abusleme,Camille Bélanger-Champagne,Alain Bellerive,Yan Benhammou,James Botte,Hadar Cohen,Merlin Davies,Yanyan Du,Lea Gauthier,Thomas Koffas,Serguei Kuleshov,Benoit Lefebvre,Changyu Li,Nachman Lupu,Giora Mikenberg,Daniel Mori,Jean-Pierre Ochoa-Ricoux,Estel Perez Codina,Sebastien Rettie,Andree Robichaud-Véronneau,Rimsky Rojas,Meir Shoa,Vladimir Smakhtin,Bernd Stelzer,Oliver Stelzer-Chilton,Alam Toro,Heberth Torres,Pablo Ulloa,Brigitte Vachon,Gerardo Vasquez,Aleksander Vdovin,Simon Viel,Pablo Walker,Stephen Weber,Chengguang Zhu
Physics , 2015,
Abstract: The instantaneous luminosity of the Large Hadron Collider at CERN will be increased up to a factor of five with respect to the present design value by undergoing an extensive upgrade program over the coming decade. The most important upgrade project for the ATLAS Muon System is the replacement of the present first station in the forward regions with the so-called New Small Wheels (NSWs). The NSWs will be installed during the LHC long shutdown in 2018/19. Small-Strip Thin Gap Chamber (sTGC) detectors are designed to provide fast trigger and high precision muon tracking under the high luminosity LHC conditions. To validate the design, a full-size prototype sTGC detector of approximately 1.2 $\times$ $1.0\, \mathrm{m}^2$ consisting of four gaps has been constructed. Each gap provides pad, strip and wire readouts. The sTGC intrinsic spatial resolution has been measured in a $32\, \mathrm{GeV}$ pion beam test at Fermilab. At perpendicular incidence angle, single gap position resolutions of about $50\,\mathrm{\mu m}$ have been obtained, uniform along the sTGC strip and perpendicular wire directions, well within design requirements. Pad readout measurements have been performed in a $130\, \mathrm{GeV}$ muon beam test at CERN. The transition region between readout pads has been found to be $4\,\mathrm{mm}$, and the pads have been found to be fully efficient.
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