359 research outputs found
Zooplankton of Western Lake Erie at Put-In-Bay: A Quantitative Study, April 1973 - March 1974
Author Institution: Center for Lake Erie Area Research, The Ohio State UniversityREUTTER, VERONICA M. AND JEFFREY M. REUTTER. Zooplankton of western Lake Erie at Put-in-Bay: a quantative study, April 1973-March 1974. Ohio J. Sci. 75(5): 256, 1975
Kapitalmarkt – Recht und Transaktionen XV
Der vorliegende Tagungsband «Kapitalmarkt – Recht und Transaktionen» fokussiert wie immer auf aktuelle Entwicklungen im Bereich Finanz- und Kapitalmarktrecht unter besonderer Berücksichtigung von Transaktionen. Das Jahr 2019 war geprägt von einem stark wachsenden Bewusstsein für soziale und ökologische Themen, das auch vor Investoren nicht Halt gemacht hat. Eine wichtige Rolle spielten zudem der sich beschleunigende technologische Fortschritt und das sich anbahnende Ende des LIBOR. Entsprechend liegt der von den Herausgebern gesetzte Schwerpunkt auf Corporate Social Responsibility, der LIBOR-Ablösung und den zivil- und finanzmarktrechtlichen Aspekten der DLT-Vorlage des Bundesrates im Bereich Blockchain. Daneben erhalten auch traditionelle Themen wie Rechtsfragen im Zusammenhang mit Börsengängen und Analyst Reports Raum in diesem Band
Non-linear model for the simulation of viscously damped RF-MEMS switches at varying ambient pressure conditions
AbstractWe present a physically-based multi-energy domain coupled model that allows for the predictive simulation of the dynamic response of electrostatically controlled and viscously damped RF-MEMS switches. The coupling effects occurring during dynamic operation, namely increased damping due to the decreasing gap height and electrostatic spring softening are correctly implemented in the model and, therefore, accurately reproduced. The model is able to account for varying ambient pressure conditions and shows good agreement with measurements ranging from 960hPa down to approx. 200hPa
Die Rolle des alphaL/beta2 Integrins LFA-1 in der T-Zell-Antigenrezeptor- abhängigen Proliferation primärer humaner T Lymphozyten
Cover and Contents
1\. Introduction
1.1 Interdependence between adhesion and proliferation: The role of integrins
in anchorage-dependent proliferation of non-lymphoid cells 6
1.2 T lymphocyte activation 12
1.3 The role of integrins and other costimulatory receptors in T cell
activation 16
1.4 Aims of the study 19
2\. Material and methods
2.1 Purification of primary human T cells 20
2.2 Stimulation of primary T cells 21
2.3 Propidium iodide staining 22
2.4 Immunofluorescence 23
2.5 F-actin staining 23
2.6 Cloning of the glutathione-S-transferase - intercellular adhesion molecule
1 fusion protein (GST-ICAM) 23
2.7 Competence induction and transformation of E. coli 25
2.8 Expression, purification and protease cleavage of GST fusion proteins 26
2.9 Purification of monoclonal antibodies 27
2.10 Sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE), band
shift assay, Coomassie- staining and immunoblotting 27
2.11 Protein determination 28
2.12 Preparation of sub-cellular fractions 29
2.13 Immunprecipitation 29
2.14 In-vitro kinase assays 30
2.15 RNA preparation and Northern blotting 31
2.16 Enzyme Linked Immuno-Sorbent Assay (ELISA) 32
2.17 Electroporation of primary T cells 33
2.18 Electrophoretic mobility shift assay 34
3\. Results
3.1 Proliferation in response to TCR cross-linking requires LFA-1-dependent
spreading in quiescent human T cells. 36
3.2 The antibody-induced internalization of the TCR does not correlate with
LFA-1-dependent proliferation 39
3.3 Tyrosine phosphorylation is synergistically induced by TCR triggering and
LFA-1-mediated spreading 41
3.4 Regulation of MAP kinases by LFA-1 and the TCR in primary human T cells 43
3.5 Effects of LFA-1 on the expression of the immediate early genes c-fos and
c-jun. 47
3.6 LFA-1-mediated spreading is a required late component for S phase entry in
TCR-stimulated cells 48
3.7 Sustained LFA-1-dependent spreading promotes pRb-inactivation 50
3.8 LFA-1-dependent Interleukin-2 production mediates G1 to S transition. 52
3.9 CD28 aggregation can bypass the late LFA-1- dependent step of anchorage-
dependent T cell growth 55
3.10 Co-engagement of either CD28 or LFA-1 induces cyclosporin A-resistant
proliferation 56
3.11 The in vitro binding of transcription factors to the IL-2 promoter is not
differentially affected by cyclosporin A in TCR- and costimulated cells 58
4\. Discussion
4.1 Summary 61
4.2 The experimental system 62
4.3 The role of tyrosine phosphorylation in LFA-1-dependent signalling and
proliferation 65
4.4 The role of spreading-dependent Map kinase activation in T cell
proliferation 66
4.5 Costimulation mediates cyclosporin A-resistant G1 to S transition: The
role of IL-2 69
4.6 The presumed role of LFA-1 in T cell proliferation in a physiological
intercellular contact 71
Abbreviations 75
Acknowledgements 78
References 79
Zusammenfassung 93
Curriculum vitae 95Summary In this study, the role of the alphaL/beta2-integrin leukocyte
function antigen-1(LFA-1) in the proliferation of T cell antigen
receptor(TCR)-stimulated primary human T lymphocytes was analyzed. Co-
engagement of LFA-1 was found to be a prerequisite for proliferation in TCR-
stimulated cells in the absence of other receptor-ligand interactions. The
effect of LFA-1 on cell cycle progression can not simply be explained with
enhanced adhesion-dependent TCR triggering, but is mediated by TCR-independent
signal transduction. As reported for non-lymphoid, anchorage-dependent cell
types, the integrin-mediated signal transduction and proliferation critically
depend on an intact actin-based cytoskeleton and a spread cell shape rather
than on receptor aggregation. The pro-mitotic effects of LFA-1 act at two
distinct points on cell cycle progression: In the Gap 0 phase of the cell
cycle, LFA-1-mediated spreading synergizes with the TCR on tyrosine
phosphorylation, leading to enhanced mitogen-activated protein(Map) kinase
activation, immediate early gene expression, cell cycle entry and the
induction of responsiveness to the T cell growth factor Interleukin 2 (IL-2).
However, LFA-1 was found to be as well a required late component of TCR-
dependent proliferation: Prolonged LFA-dependent spreading, in the context of
intercellular contact, is a prerequisite for the production of the mitogenic
cytokine Interleukin-2. LFA-1-dependent IL-2 production was found to be
cyclosporin A-resistant and was paralleled by the enhanced binding of
transcription factors to the NF-AT and the CD28RE/AP-1 site of the IL-2
promoter in vitro. The alternative costimulatory receptor CD28 is able to
bypass this step in an adhesion-independent way. IL-2 in turn triggers the
expression of the a-chain of the IL-2 receptor (CD25), and leads to the
activation of cyclin-dependent kinases (CDKs), probably due to enhanced cyclin
D3 expression and to the downregulation of the CDK inhibitor p27kip1. The
activation of the CDKs leads to the inactivating phosphorylation of the
retinoblastoma protein (pRb) and to the progression into the synthesis(S)
phase of the cell cycle. Anchorage-dependent T cell growth is therefore
characterized by a sequential action of signals conveyed by integrins which
together with the activating antigenic stimulus effects both cell cycle entry
and G1 to S transition.Das Thema der vorliegenden Arbeit ist die Rolle des alphaL/beta2 integrins
"lymphocyte function-associated antigen-1" (LFA-1) in der T-Zell-
Antigenrezeptor(TCR)-abhängigen Proliferation von primären humanen
T-Lymphozyten. Die Stimulierung von LFA-1 erwies sich als notwendige Bedingung
der TCR-stimulierten Proliferation in Abwesenheit anderer Rezeptor-Liganden
Wechselwirkungen. Die LFA-1-abhängige Proliferation ist nicht alleine durch
die adhäsionsbedingte Verstärkung der TCR-Stimulierung zu erklären, sondern
beruht auf TCR-unabhängiger Signaltransduktion. Analog zu der Integrin-
vermittelten Signaltransduktion in adhärenten Zellen beruht auch die
LFA-1-vermittelte auf der zytoskelett-abhängigen Induktion einer abgeflachten
Zellform ("spreading") und nicht nur auf der Rezeptoraggregation. LFA-1
beeinflußt in zwei unterschiedlichen Phasen die Zellzyklusprogression: In der
G0-Phase bewirken die TCR-Stimulierung und die LFA-1-bedingte Reorganisation
des Zytoskeletts eine synergistische Aktivierung von
Tyrosinphosphorylierungen, die zu einer verstärkten Aktivierung der "mitogen-
activated protein" (Map) kinasen und veränderter Genexpression führen. Diese
resultiert dann in Zellzykluseintritt und der Fähigkeit, auf die Präsenz des T
-Zell-Wachstumsfaktors Interleukin-2 mit Zellzyklusprogression zu reagieren
("Kompetenz"). Die LFA-1-bedingte Induktion des "spreading" ist aber auch eine
notwendige späte Komponente der TCR-abhängigen Proliferation: Lang andauerndes
"spreading" im Kontext der interzellulären Adhäsion ist eine notwendige
Bedingung für die Produktion von Interleukin-2. Interleukin-2 ist notwendig
und hinreichend um in kompetenten Zellen zur Expression der alpha-Kette des
Interleukin-2-Rezeptors (CD25) und zur Aktivierung der "Cyclin-abhängigen
Kinasen" (CDKs) zu führen, letzteres auf Grund der verstärkten Cyclin D3
Expression und der verminderten Stabilität des CDK-Inhibitors p27kip1. Die
aktivierten CDKs phosphorylieren und inaktivieren das Retinoblastom-Protein,
was letztlich zur Zellzyklusprogression führt. Die Stimulierung des
alternativen costimulatorischen Rezeptors CD28 resultiert in der
adhäsionsunabhängigen Zellzyklusprogression. Die costimulations-bedingte
Zellzyklusprogression wurde nicht von Cyclosporin A inhibiert und wurde von
der verstärkten in vitro Bindung von Transkriptionsfaktoren an den
Interleukin-2 Promotors begleitet. Adhäsionsabhängige ("anchorage-dependent")
T-Zell Proliferation ist daher durch eine sequentielle Wirkung der integrin-
vermittelten Signaltranduktion gekennzeichnet, die zusammen mit dem
aktivierenden antigenen Stimulus sowohl den Zellzykluseintritt als auch die
-progression reguliert. Auf Grund der erhaltenen Ergebnisse und der zitierten
Literatur wird das Modell der bedingten Adhäsionsabhängigkeit der T-Zell
Proliferation vorgeschlagen: Die Stärke der TCR-Stimulation, alternative
costimulatorischer Wechselwirkungen und die verfügbaren Zytokine bedingen, ob
LFA-1-bedingtes "spreading" für die T-Zell Aktivierung notwendig ist oder
nicht
Gas Flow in Hot Porous Materials: The Solar Air Receiver and Spin-Off Applications
This article presents an overview on research results from various projects, which deal with one common problem: gas flow in hot porous materials. First, the solar air receiver, which converts concentrated solar radiation into heat in an air circuit, is described as far as the basic principle and the materials employed are concerned. Then, results from experiments in concentrated solar radiation are presented. Materials employed in these applications are extruded ceramic materials as well as metal and ceramic foams with pore sizes on the milli- and micrometer scale. As it turned out, the material properties significantly influence the efficiency of the solar air receiver. It is shown, that under specific conditions flow instability occurs, which may lead to a thermal overload of the material. Measures to avoid these overloads are proposed. Two approaches how to predict gas flow theoretically are reported. Additionally, it is shown, how material quantities such as pressure drop characteristics influence the flow behaviour and the temperature distribution inside the material. Finally, before a conclusion is given, two further applications, which have been dealt with because similar phenomena occur, are reported: an advanced cross flow particle filter and a gas turbine cooling system
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