Refine
Has Fulltext
- yes (104)
Is part of the Bibliography
- yes (104)
Year of publication
- 2009 (104) (remove)
Document Type
- Doctoral Thesis (93)
- Journal article (8)
- Master Thesis (2)
- Book article / Book chapter (1)
Language
- English (104) (remove)
Keywords
- Signaltransduktion (5)
- Elementarteilchenphysik (3)
- Genexpression (3)
- Organisches Molekül (3)
- Thrombozyt (3)
- Actin-bindende Proteine (2)
- Ameisen (2)
- Aminosäuren (2)
- Apoptose (2)
- Autonomer Roboter (2)
- Dünne Schicht (2)
- Enzym (2)
- Genanalyse (2)
- Genregulation (2)
- Hautflügler (2)
- Hymenoptera (2)
- Immunreaktion (2)
- Insekten (2)
- Maus (2)
- Metabolism (2)
- Metabolismus (2)
- Metapopulation (2)
- Mobiler Roboter (2)
- Nichtlineare Optimierung (2)
- Nichtlineare Spektroskopie (2)
- Organischer Halbleiter (2)
- Pflanzenfressende Insekten (2)
- Phosphorylierung (2)
- Röntgenspektroskopie (2)
- Spektroskopie (2)
- Starke Kopplung (2)
- Symmetrie (2)
- T-Lymphozyt (2)
- Zellzyklus (2)
- gas phase (2)
- metapopulation (2)
- perylene bisimide (2)
- signal transduction (2)
- (S (1)
- (Signal transduction pathways) (1)
- 1 (1)
- 10-bis(dicarboximide)> (1)
- 1H-NMR-Spectroscopy (1)
- 2 (1)
- 3 (1)
- 3-pentafluoropropene (1)
- 3-tetrafluoropropene (1)
- 4:9 (1)
- A-RAF (1)
- AFM (1)
- AMPK (1)
- ARF6 GTPase (1)
- Abscisic Acid (1)
- Abscisinsäure (1)
- Abstiegsverfahren (1)
- Abwehr (1)
- Acrylamid (1)
- Acrylamide (1)
- Actin binding proteins (1)
- Actin-Polymerisation (1)
- Active galactic nuclei (1)
- Affective Startle Modulation (1)
- Affekt (1)
- Affektive Schreckreflexmodulation (1)
- Aggregat <Chemie> (1)
- Aggregation (1)
- Aktiver galaktischer Kern (1)
- Algebraischer Funktionenkörper (1)
- Allgemeine Relativitätstheorie (1)
- Ammoniten (1)
- Amphibolit (1)
- Angewandte Linguistik (1)
- Antennallobus (1)
- Antikörper (1)
- Antonym (1)
- Apoptosis (1)
- Approximationsalgorithmus (1)
- Arbeitsmarkttheorie (1)
- Arbeitsteilung (1)
- Arzneimitteldesign (1)
- Astronomische Beobachtung (1)
- Aufmerksamkeits-Defizit-Syndrom (1)
- Austauschaufspaltung (1)
- Autonomous multi-vehicle systems (1)
- Außenhandel (1)
- B-Zellen (1)
- BCL2 (1)
- BL-Lacertae-Objekt (1)
- BL-Lacertae-object (1)
- Bacterial (1)
- Bajocium (1)
- Bathonium (1)
- Behaviour (1)
- Bestandsmanagement (1)
- Bestärkendes Lernen <Künstliche Intelligenz> (1)
- Bewegungskoordination (1)
- Bewegungsverhalten (1)
- Biene (1)
- Bindungsanalyse (1)
- Biogenese (1)
- Bioinformatik (1)
- Biopolymere (1)
- Biotransformation (1)
- BitTorrent (1)
- Blattkäfer (1)
- Blinear Quantum Control Systems (1)
- Borneo (1)
- Borrelia (1)
- Borylenkomplexe (1)
- Brain (1)
- Breitbandseismologie (1)
- Buckminsterfulleren (1)
- Bushveld Complex (1)
- Bushveld Komplex (1)
- C-RAF (1)
- CD-Spektroskopie (1)
- CKM-Matrix (1)
- Cadmiumselenid (1)
- Calcium-bindende Proteine (1)
- Carcinogenese (1)
- Catalyst (1)
- Catechol-O-Methyltransferase (COMT) (1)
- Central Nervous System (1)
- Chaperone (1)
- Checkpoint adaptation (1)
- Checkpoint recovery (1)
- Chemische Kommunikation (1)
- Chemische Synthese (1)
- Chemokine Receptor (1)
- Chemokinrezeptors (1)
- Chlamydia trachomatis (1)
- Chorasan (1)
- Chrysomelidae (1)
- Cognitive Model (1)
- Coleoptera (1)
- Commodity Markets (1)
- Computersimulation (1)
- Conservation Laws (1)
- Content Distribution (1)
- Controllability (1)
- Copula (1)
- Cyaninfarbstoff (1)
- Cytokinin (1)
- Cytokinine (1)
- Cytokinins (1)
- Cytoplasma (1)
- Cytoplasmic Ca"+ (1)
- Cytoskeleton (1)
- D-Norm (1)
- DFT (1)
- DNA damage response (1)
- DNA-Schadensantwort (1)
- DNS-Reparatur (1)
- DNS-Schädigung (1)
- Das Andere (1)
- Degeneration (1)
- Delay Discounting (1)
- Deutschland / Gesetz für moderne Dienstleistungen am Arbeitsmarkt 4 (1)
- Deutschland / Gesetz zu Reformen am Arbeitsmarkt (1)
- Dezentrale Regelung (1)
- Dienstgüte (1)
- Differenzierung (1)
- Dopamin (1)
- Doppelhelix (1)
- Dorso-ventral Patterning (1)
- Drosophila (1)
- Dunkle Materie (1)
- Dünnschichttransistor (1)
- ELF (1)
- EPR (1)
- ERK (1)
- ERT (1)
- Edge-based Intelligence (1)
- Effizienter Algorithmus (1)
- Egypt (1)
- Eink (1)
- Eiparasitismus (1)
- Elektronenstruktur (1)
- Elektronische Eigenschaft (1)
- Embryo (1)
- Emotional Facial Expressions (1)
- Emotionaler Gesichtsausdruck (1)
- Endocytose (1)
- Endosymbiont (1)
- Energiedispersive Röntgenspektroskopie (1)
- Energielücke (1)
- Enterobacteriaceae (1)
- Entmarkung (1)
- Entwicklungsbiologie (1)
- Entzündung (1)
- Enzyme (1)
- Enzyminhibitor (1)
- Erhaltungsgleichungen (1)
- Eulophidae (1)
- Europe (1)
- Evaluation (1)
- Evolutionsbiologie (1)
- Excited-State Dynamics of Organic Intermediates (1)
- Extra Dimensions (1)
- Extradimensionen (1)
- Extremwertverteilung (1)
- FIONA (1)
- Fabry’s disease (1)
- Farbstoff (1)
- Faziesanalyse (1)
- Feldeffekttransistor (1)
- Femtosekunden (1)
- Fernerkundung (1)
- Fettsäure-Synthase (1)
- Fische (1)
- Flavor Symmetrie (1)
- Flavour <Elementarteilchen> (1)
- Flavour <Elementarteilchenphysik> (1)
- Flavour Changing Neutral Currents (1)
- Flavourmischung (1)
- Fluorescence imaging with one nanometer accuracy (1)
- Fluoreszenz (1)
- Fn14 (1)
- Formation (1)
- Formationsbewegung (1)
- Formicidae (1)
- Fourier-Spektroskopie (1)
- Fragmentierung (1)
- Frucht (1)
- Fruchtansatz (1)
- Fruchtentnahme (1)
- Fruchtgehalt (1)
- Fruchtproduktion (1)
- Fruchtqualität (1)
- Funktionelle NMR-Tomographie (1)
- Future Internet (1)
- GC-MS (1)
- GC/MS (1)
- GPD (1)
- GPD-Flow (1)
- GUT (1)
- Galeruca tanaceti (1)
- Galois-Erweiterung (1)
- Galois-Feld (1)
- Gammastrahlung (1)
- Gas-Phase (1)
- Gehirn (1)
- Gelieren (1)
- Gen-/Genomverdoppelung (1)
- General Oligopolistic Equilibrium (1)
- Generalisierte Lineare Modelle (1)
- Genomik (1)
- Geoinformationssystem (1)
- Germany (1)
- Geruchswahrnehmung (1)
- Gletscher (1)
- Gletscherrückzug (1)
- Globalisierung (1)
- Glomeruli (1)
- Glukose (1)
- Glut4 (1)
- Glutathion S-Konjugat (1)
- Granulit (1)
- Granulitfazies (1)
- Graph (1)
- Gravitationswelle (1)
- Grenzflächenaktiver Stoff (1)
- Groundwater (1)
- Großbritannien (1)
- Große Vereinheitlichung (1)
- Grundwassermodelle (1)
- Guanidinderivate (1)
- Guanidiniocarbonylpyrrol (1)
- Guard Cell (1)
- H-bonds (1)
- HDL (1)
- HLA-G (1)
- HOMOGENIZED (1)
- Habitat fragmentation (1)
- Halbleiterschicht (1)
- Hamilton Systeme (1)
- Hamilton Sytstems (1)
- Hartz-Reform (1)
- Heart Rate Variability (1)
- Herzratenvariabilität (1)
- Hidden-Markov-Modell (1)
- Higgsless Models (1)
- Higgslose Modelle (1)
- High-temperature superconductivity (1)
- Higher Order Corrections (1)
- Hirnforschung (1)
- Hochtemperatursupraleiter (1)
- Honeybee (1)
- Horizontaler Unternehmenszusammenschluss (1)
- Host-parasite interactions (1)
- Hubbard model (1)
- Hubbard-Modell (1)
- Hydrodynamische Grenzwerte (1)
- Hydrogeologie (1)
- Hyperonymie (1)
- IAP (1)
- IENFD (1)
- IG-FET (1)
- IPES (1)
- Ichnologie (1)
- Ichnology (1)
- Illustration (1)
- Immunantwort (1)
- Immunesupression (1)
- Immunoreceptors (1)
- Immunrezeptoren (1)
- Immunsupression (1)
- Immunsystem (1)
- Immunzellen (1)
- Impulsivität (1)
- Inhalation (1)
- Innovation Incentives (1)
- Innovationswettbewerb (1)
- Interferon (1)
- Interferonantagonism (1)
- Interferonantagonismus (1)
- Intermediate (1)
- Interspezifische Assoziation (1)
- Intrazellulärraum (1)
- Intuition (1)
- Inventar (1)
- Inventory Dynamics (1)
- Inverse Photoemissions (1)
- Iran (1)
- J-Aggregat (1)
- J-aggregate (1)
- Java 2 Enterprise Edition (1)
- Judit <Buch> (1)
- Judith <Book> (1)
- Kashafrud (1)
- Katalysator (1)
- Keimzentrum (1)
- Kern (1)
- Kleine Eiszeit (1)
- Klima (1)
- Klimaänderung (1)
- Kluftaquifer (1)
- Knockout <Molekulargenetik> (1)
- Knowledge (1)
- Kognition (1)
- Kognitive Linguistik (1)
- Kognitive Semantik (1)
- Kohlenwasserstoffe (1)
- Kollinearität (1)
- Kolonieerkennung (1)
- Kombinatorische Synthese (1)
- Kontrolltheorie (1)
- Konvexe Analysis (1)
- Konzentration <Wirtschaft> (1)
- Kooperierende mobile Roboter (1)
- Kopula <Mathematik> (1)
- Korpus <Linguistik> (1)
- Korrelation (1)
- Kraftmikroskopie (1)
- Krebs <Medizin> (1)
- Krebstherapie (1)
- Kristallstruktur (1)
- LHC (1)
- LIN-9 (1)
- LINC (1)
- Laborexperiment (1)
- Leber (1)
- Legionella pneumophila (1)
- Leistungsbewertung (1)
- Lie-Gruppe (1)
- Limpopo Belt (1)
- Limpopo-Gürtel (1)
- Lin (1)
- Lindblad-Kossakowski Master Equation (1)
- Lineare Regression (1)
- Linguistik (1)
- Little Ice Age (1)
- Locomotion (1)
- Logik des Entailment (1)
- Luftwelle (1)
- Lyme disease (1)
- Lyme-Borreliose (1)
- MAPK (1)
- MASim (1)
- MCP-1 (1)
- MPEC (1)
- MPVC (1)
- Macromolecular Complex (1)
- Magnetismus (1)
- Makrobenthos (1)
- Makromolekül (1)
- Makrophage (1)
- Marktkonzentration (1)
- Maschine (1)
- Massenmatrix (1)
- Master-Gleichung (1)
- Matching-Modell (1)
- Mathematische Modellierung (1)
- Mediator (1)
- Meeresmikroseismik (1)
- Mehragentensystem (1)
- Mehrfahrzeugsysteme (1)
- Melanin (1)
- Membranproteine (1)
- Mergers and Acquisitions (1)
- Merkaptolaktat (1)
- Merkaptursäure (1)
- Mesencephalon (1)
- Metabonomics (1)
- Metakognition (1)
- Metall-Halbleiter-Kontakt (1)
- Metalloproteases (1)
- Metalloproteinasen (1)
- Metamorphose <Geologie> (1)
- Methyllithium (1)
- Microarray (1)
- Migration (1)
- Mimik (1)
- Mitose (1)
- Mittelhirn (1)
- Modellierung (1)
- Modelling (1)
- Molecular Machine (1)
- Molekularbewegung (1)
- Molekulare Erkennung (1)
- Molekulare Evolution (1)
- Molekül (1)
- Molekülsymmetrie (1)
- Molekülzustand (1)
- Monodromie (1)
- Morpholino (1)
- Motoneuron (1)
- Multi-Network Service (1)
- Multi-Netzwerk Dienste (1)
- Multidrug-Resistenz (1)
- Multiple Sclerosis (1)
- Multiplen Sklerose (1)
- Multiproteinkomplex (1)
- Multivariate Analyse (1)
- Mutante (1)
- Mutualismus (1)
- Myb (1)
- Myelin (1)
- NES (1)
- NEXAFS (1)
- NFkappaB (1)
- NIR-Spektroskopie (1)
- NLS (1)
- NMR-Spektroskopie (1)
- NP-hardness (1)
- NP-hartes Problem (1)
- Nash Equilibrium Problem (1)
- Nash-Gleichgewicht (1)
- Natriumhydroxid (1)
- Neuralleiste (1)
- Neuronal Proliferation (1)
- Neurotransmitter (1)
- Neutrinooszillation (1)
- Newton Methods (1)
- Newton-Verfahren (1)
- Nichtglatte Analysis (1)
- Nichtglatte Optimierung (1)
- Nichtholonome Fahrzeuge (1)
- Nichtkonvexe Optimierung (1)
- Nichtlineare Regelung (1)
- Niere (1)
- Nikaido-Isoda Funktion (1)
- Nikaido-Isoda function (1)
- Non Hodgkin Lymphoma (1)
- Non Hodgkin Lymphome (1)
- Norway (South) (1)
- Norwegen <Süd> (1)
- OFET (1)
- Oberkreide (1)
- Oligopol (1)
- Onbead-Enzymscreening (1)
- Onkologie (1)
- Oomyzus galerucivorus (1)
- Ophiolite (1)
- Ophiolith (1)
- Optik (1)
- Optimale Kontrolle (1)
- Optische Anisotropie (1)
- Optische Spektroskopie (1)
- Oralsekret (1)
- Orbitofrontaler Kortex (OFC) (1)
- Organische Synthese (1)
- Organischer Feldeffekttransistor (1)
- Overlay-Netz (1)
- P-T Entwicklung (1)
- P-T pseudosections (1)
- PKA (1)
- PKG (1)
- PMNS (1)
- PMP22 (1)
- Parabiose (1)
- Parametrisierung (1)
- Parasit (1)
- Particle Physics (1)
- Pathogenese (1)
- Pax3 (1)
- Pax7 (1)
- Peer-to-Peer-Netz (1)
- Peptidsynthese (1)
- Periphere Nerven (1)
- Perylenbisdicarboximide <Perylen-3 (1)
- Perylenbisimid (1)
- Perylenderivate (1)
- Pflanzen (1)
- Pflanzenhormon (1)
- Phasendiagramme (1)
- Phenomenology (1)
- Pheromone (1)
- Photoelektronenspektroskopie (1)
- Photosystem II (1)
- Physics Beyond the Standard Model (1)
- Physik jenseits des Standardmodells (1)
- Physiologie (1)
- Phytoalexin (1)
- Phytoalexine (1)
- Phytoalexins (1)
- Phytohormone (1)
- Phänomenologie (1)
- Pigmentierung (1)
- Plant Hormones (1)
- Plant immunity (1)
- Platelets (1)
- Polymorphismus (1)
- Polysemie (1)
- Porin (1)
- Preisänderung (1)
- Prion (1)
- Prionkrankheit (1)
- Prospect Theory (1)
- Protonen-NMR-Spektroskopie (1)
- Pseudomonas syringae (1)
- Pseudomonas syringae pv. tabaci (1)
- Q-Learning (1)
- QST (1)
- QTAIM (1)
- Quality of Experience QoE (1)
- Quantenchemie (1)
- Quantenchromodynamik (1)
- Quantendynamik (1)
- Quantenmechanisches System (1)
- Quantenpunkt (1)
- RAF kinases (1)
- RIXS (1)
- RNS (1)
- RS1 (1)
- Rab23 (1)
- Raf <Biochemie> (1)
- Raf-Kinasen (1)
- Randall-Sundrum (1)
- Rasmussen-Syndrom (1)
- Reaktionsmechanismus (1)
- Recycling- Endosomen (1)
- Regenwald (1)
- Registrierung <Bildverarbeitung> (1)
- Regressionsanalyse (1)
- Regulation (1)
- Regulatorische T-Zellen (1)
- Regulatory T cells (1)
- Rendezvous (1)
- Replikation (1)
- Resource Managment (1)
- Ressourcenmanagement (1)
- Rheumatoid arthritis (1)
- Rheumatoider arthritis (1)
- Rho GTPase (1)
- Rho GTPasen (1)
- Ridge-Regression (1)
- Risikobewertung (1)
- Risk Assessment (1)
- Robotik (1)
- Route Choice (1)
- Route Entscheidung (1)
- Röntgenabsorptionsspektroskopie (1)
- Röntgenstrahlung (1)
- Rückfallfieber (1)
- SGLT1 (1)
- SOC (1)
- SOCE (1)
- STIM2 (1)
- Samenverbreitung (1)
- Satellitenfernerkundung (1)
- Scheibe-Aggregat (1)
- Schließzelle (1)
- Schwann Zellen (1)
- Schwann cells (1)
- Sedimentary (1)
- Seismisches Array (1)
- Seismologie (1)
- Seismometer (1)
- Selbst (1)
- Selbstaktivierung (1)
- Selbstorganisation (1)
- Semantische Relation (1)
- Semi-Markov-Prozess (1)
- Sequence Analysis (1)
- Sequenzanalyse (1)
- Serotonin (1)
- Shakespeare (1)
- Shakespeare illustration (1)
- Shakespeare-Illustration (1)
- Shh (1)
- Signal-Übertragung (1)
- Signalkaskade (1)
- Siliciumhalbleiter (1)
- Simulation (1)
- Sintern (1)
- Skalierung (1)
- Skype (1)
- Small nuclear RNP (1)
- Social Anxiety (1)
- Social role (1)
- Sociality (1)
- Sozialangst (1)
- Soziale Rolle (1)
- Soziale Wohlfahrt (1)
- Sozialität (1)
- Species Differences (1)
- Speziesunterschiede (1)
- Spezifikation (1)
- Spieltheorie (1)
- Spirochäten (1)
- Spurpheromone (1)
- Standardmodell <Elementarteilchenphysik> (1)
- Standortproblem (1)
- Steuerung (1)
- Store-Operated (1)
- Stratigraphie (1)
- Stratigraphy (1)
- Stress (1)
- Stromboli (1)
- Supersymmetrie (1)
- Supramolekulare Chemie (1)
- Supramolekulare Struktur (1)
- Symbiose (1)
- Synonymie (1)
- Synthetischer Farbstoff (1)
- Systembiologie (1)
- T cell (1)
- T lymphocyte (1)
- TRAF2 (1)
- TTF (1)
- TWEAK (1)
- Tamarin (1)
- Taufliege (1)
- Taxonomie (1)
- Textur (1)
- Theoretical Physics (1)
- Theoretische Chemie (1)
- Theoretische Physik (1)
- Theoretische Ökologie (1)
- Therapie (1)
- Thermoregulation (1)
- Thiophen (1)
- Thiophenderivate (1)
- Thrombose (1)
- Thrombosis (1)
- Tiplet emiters (1)
- Tiplett Emitter (1)
- Topologieoptimierung (1)
- Totenkopfäffchen (1)
- Toxicokinetics (1)
- Toxicology (1)
- Toxikokinetik (1)
- Toxikologie (1)
- Toxizität (1)
- Traffic (1)
- Transitive Lie Groups (1)
- Transplantation (1)
- Transportprozess (1)
- Tremor (1)
- Troodos (1)
- Tuberkelbakterium (1)
- Tumor-Nekrose-Faktor (1)
- UPS (1)
- UV-VIS-Spektroskopie (1)
- Ubiquitination (1)
- Ubiquitinierung (1)
- Ultrakurzzeitspektroskopie (1)
- Ultraviolett-Photoelektronenspektroskopie (1)
- Unstetige Regelung (1)
- Unterholz (1)
- Unternehmenszusammenschluss (1)
- Upper Cretaceous (1)
- VIS-Spektroskopie (1)
- Vasodilatator-stimuliertes Phosphoprotein (1)
- Verarbeitungsflüssigkeit (1)
- Verhaltensanalyse (1)
- Verstärkung (1)
- Vertebrat (1)
- Verteilung von Inhalten (1)
- Vicia (1)
- Viren (1)
- Vulkan (1)
- Vulkanisches Beben (1)
- Vulkanseismologie (1)
- Warped Space (1)
- Warteschlangentheorie (1)
- Wasserhaushalt (1)
- Wasserreserve (1)
- Wasserstoffbrücken (1)
- Wasserstoffbrückenbindung (1)
- Waterbalance (1)
- Wettbewerbsstrategie (1)
- Wide-gap-Halbleiter (1)
- William (1)
- Wirt (1)
- Wissenserwerb (1)
- WordNet (1)
- Würzburg / Institut für Paläontologie (1)
- XAS (1)
- XES (1)
- XIAP (1)
- ZRP (1)
- Zellskelett (1)
- Zellwand (1)
- Zentralnervensystems (1)
- Zero Range Prozess (1)
- Ziel (1)
- Zinkselenid (1)
- Zuckerrübeneule (1)
- Zwischenmolekulare Kraft (1)
- Zypern (1)
- acute stress (1)
- air wave (1)
- algebraic function field (1)
- algorithm (1)
- amino acids (1)
- ammonites (1)
- antennal lobe (1)
- anti-predator defence (1)
- approximation algorithm (1)
- astronomical observation (1)
- bacterial (1)
- bias (1)
- biosurfactants (1)
- bispecific antibody (1)
- bispezifische Antikörper (1)
- blow out (1)
- bond analysis (1)
- borylene complexes (1)
- broadband seismology (1)
- cancer therapy (1)
- car-like robots (1)
- cardiac hypertrophy (1)
- cardiac metabolism (1)
- caterpillars (1)
- cell cycle (1)
- cell wall (1)
- charge separation (1)
- chemical ecology (1)
- chemische Ökologie (1)
- collinearity (1)
- competitive location (1)
- composites (1)
- crystal structure (1)
- degeneration (1)
- demographic stochasticity (1)
- diagnostic Microarray (1)
- diagnostischer Microarray (1)
- distant dipolar field (1)
- doppelsträngige RNA (1)
- double-stranded RNA (1)
- drug development (1)
- dvision of labor (1)
- efficient algorithm (1)
- electronic (1)
- electronisch (1)
- endocytic recycling (1)
- environment Late Bajocian Late Bathonian (1)
- enzymatic synthesis (1)
- estrogen (1)
- estrogen receptor (1)
- evaluation (1)
- exciton binding energy (1)
- facies analysis (1)
- fatty acid synthesis (1)
- feelings as informations (1)
- femtosecond (1)
- finite fields (1)
- fish (1)
- flavor symmetry (1)
- fluorocarbons (1)
- flux (1)
- formation driving (1)
- four-wave mixing (1)
- fruit crop size (1)
- fruit removal (1)
- galois extensions (1)
- gamma radiation (1)
- gene expression (1)
- gene regulation (1)
- gene/genome duplication (1)
- genomic (1)
- genomics (1)
- glacier (1)
- glomeruli (1)
- glucose (1)
- glutathion S-conjugate (1)
- goals (1)
- granulite facies (1)
- graph (1)
- graph decomposition (1)
- gravitational waves (1)
- guanidiniocarbonyl pyrrole (1)
- herbivore (1)
- horizontal merger (1)
- host plant density (1)
- hybrid imaging (1)
- hydrocarbons (1)
- immune cells (1)
- immune system (1)
- in vivo MR-Spektroscopy (1)
- individual-based model (1)
- individual-based simulation (1)
- inegrierte Stratigraphie (1)
- inflammation (1)
- inhalation (1)
- innate immunity (1)
- insect (1)
- integrated stratigraphy (1)
- intelligente Applikationen (1)
- intermediate (1)
- intermolecular interaction (1)
- intermolecular zero-quantum coherence (1)
- interspecific association (1)
- intuitive Urteile (1)
- intuitive judgments (1)
- inventory (1)
- kidney (1)
- knockout (1)
- konjugiert (1)
- labor market reform (1)
- ladungsgetrennte Zustände (1)
- laser (1)
- liquid cell (1)
- liquids (1)
- liver (1)
- macrobenthos (1)
- magnetism (1)
- market concentration (1)
- mass matrix (1)
- matching model (1)
- membrane protein (1)
- membrane trafficking (1)
- memory B cells (1)
- mercaptolactic acid (1)
- mercapturic acid (1)
- metabolic (1)
- metabolites (1)
- metamorphism (1)
- methyllithium (1)
- mitogen cascade (1)
- mobile robots (1)
- model predictive control (1)
- modelling (1)
- monodromy groups (1)
- mouse (1)
- multi-drug-resistance (1)
- multi-vehicle formations (1)
- multi-vehicle rendezvous (1)
- multitrophic (1)
- multivariate Extreme Value Distribution (1)
- multivariate analysis (1)
- nestmate recognition (1)
- network (1)
- neural crest (1)
- neuropathic pain (1)
- nicht-kovalente Wechselwirkungen (1)
- non-covalent interactions (1)
- nonholonomic vehicles (1)
- nuclear export signal (1)
- nuclear localization signal (1)
- nucleus (1)
- ocean microseisms (1)
- olfaktorische Rezeptorneurone (1)
- onbead enzym screening (1)
- optical polarization conversion (1)
- optimale Suchleistung (1)
- orbitofrontal cortex (OFC) (1)
- organic molecule (1)
- organic molecules (1)
- organic semiconductor (1)
- organic semiconductors (1)
- organogelator (1)
- p100 (1)
- paleoecology (1)
- parabiosis (1)
- parameterization (1)
- pathogenesis (1)
- pathway (1)
- peripheral nerves (1)
- pheromone (1)
- phosphorylation (1)
- pi-conjugated (1)
- pigmentation (1)
- plant (1)
- platelet (1)
- polymorphism (1)
- porin (1)
- preventive strategies (1)
- processing fluency (1)
- quantum dynamics (1)
- rasmussen encephalitis (1)
- receding horizon control (1)
- regression (1)
- regurgitation (1)
- relapsing fever (1)
- resolution enhancement (1)
- rheumatoide Arthritis (1)
- ridge regression (1)
- s) Order Policy (1)
- secondary metabolites (1)
- self (1)
- self-activation (1)
- self-assembly (1)
- serotonin (1)
- sex-biased dispersal (1)
- sex-specific competition (1)
- siRNA (1)
- signal trunsduction (1)
- sintering (1)
- snow shoveling (1)
- sozialer Überschuss (1)
- spectroscopy (1)
- squirrel monkeys (1)
- stratigraphy (1)
- strong correlated electrons (1)
- structure based drug design (1)
- sub-micron (1)
- sub-mikrometer (1)
- suicide prevention (1)
- supramolecular (1)
- supramolecular chemistry (1)
- supramolekular (1)
- systems biologie (1)
- tamarins (1)
- tansy leaf beetle (1)
- taphonomy (1)
- tetrafluoropropene (1)
- texture (1)
- tool (1)
- toxicity (1)
- trail pheromone (1)
- trail-sharing (1)
- trajectory planning (1)
- trans-1 (1)
- transport gap (1)
- transporter regulator (1)
- tree (1)
- tuberculosis (1)
- two-dimensional spectroscopy (1)
- ultrafast spectroscopy (1)
- ultraviolet radiation (1)
- ultraviolette Strahlung (1)
- understorey tree (1)
- vegetation structure (1)
- vertebrate (1)
- virulence (1)
- vis spectroscopy (1)
- volcano seismology (1)
- vom Nutzer erfahrene Dienstgüte QoE (1)
- voting location (1)
- welfare (1)
- x-ray absorption spectroscopy (1)
- x-ray emission spectroscopy (1)
- zukünftiges Internet (1)
- Ägypten (1)
- Ökologie (1)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (19)
- Physikalisches Institut (9)
- Graduate School of Life Sciences (8)
- Institut für Geographie und Geologie (7)
- Institut für Mathematik (7)
- Institut für Theoretische Physik und Astrophysik (7)
- Julius-von-Sachs-Institut für Biowissenschaften (6)
- Institut für Informatik (5)
- Rudolf-Virchow-Zentrum (5)
- Institut für Organische Chemie (4)
EU-Project number / Contract (GA) number
- 223138 (1)
Regulation of effector T cells is an important mechanism to control organ-specific inflammation. Thereby regulatory T cells (Treg cells) are essential for maintaining peripheral immune tolerance and for establishing parenchyma immune homeostasis. A novel population of natural human Treg characterized by the constitutive expression of the immune-tolerogenic human HLA-G molecule has been identified. In the first part of the study, we elucidated the mechanism(s) by which CD4+ HLA-Gpos Treg modulates their cellular targets namely autologous HLA-G negative responder T cells (HLAGneg Tresp). Using a suppression system free of antigen-presenting cells (APC), we demonstrate a T-T cell interaction resulting in suppression of HLA-Gneg Tresp. We could also show that this suppression was independent of cell-cell contact. Importantly, stimulus of T cell receptor (TCR) on HLA-Gpos Treg facilitated their suppressive capacity. We also observed that removal of HLA-Gpos Treg from the established co-cultures could restore the ability of HLA-Gneg Tresp to proliferate upon TCR re-stimulation, indicating that the suppression was reversible. Further, HLA-Gpos Treg–mediated suppression was critically depending on the secretion of IL-10 but not TGF-β. Taken together, this part of the work provides an in-depth characterization of the mechanisms of how HLA-Gpos Treg suppresses T responder cells in direct T-T interactions. Understanding the suppressive mechanism used by HLA-Gpos Treg may help to develop therapeutic strategies to modulate regulatory arms of T-cell suppression. In the second part of this study, the potential role of HLA-Gpos Treg in the pathophysiological process of Multiple Sclerosis (MS), a prototypic autoimmune inflammatory central nervous system (CNS), has been investigated. We found that HLA-Gpos Treg are enriched in the cerebrospinal fluid (CSF) from MS patients, but not in non-inflammatory controls. CSFderived HLA-Gpos Treg showed predominance of central memory (CD45RA-CD27+) phenotype, exhibited markers of activation (ICOS), and had significantly higher expression of the inflammatory chemokine receptor CCR5. Importantly, these cells demonstrated as potent suppressors to autologous CD4+ T-cell proliferation. Using an in vitro model of human blood brain barrier, we showed that HLA-Gpos Treg have a strong propensity to migrate, which could be facilitated by MIP1α and RANTES (ligands of CCR5) but not MIP3β (a ligand of CCR7). The HLA-Gpos Treg migration triggered by chemokines was also associated with a gain of suppressive capacity upon cellular transmigration. In contrast to CD4+CD25+ naturally occurring FoxP3-expressing Treg, HLA-Gpos Treg from patients with MS did not exhibit impaired function, suggesting that HLA-Gpos Treg are selectively recruited to the sites of CNS inflammation in an effort to combat destructive inflammation during MS. Our results contribute to the understanding of the role and function of HLA-Gpos Treg and provide an important example of “beneficial” T-cell inflammation in CNS autoimmunity- interesting both from a patho/-physiological and a therapeutically point of view.
It is well known, that the least squares estimator performs poorly in the presence of multicollinearity. One way to overcome this problem is using biased estimators, e.g. ridge regression estimators. In this study an estimation procedure is proposed based on adding a small quantity omega on some or each regressor. The resulting biased estimator is described in dependence of omega and furthermore it is shown that its mean squared error is smaller than the one corresponding to the least squares estimator in the case of highly correlated regressors.
The main focus of this thesis was the synthesis and analysis of multifunctional oligopeptides. The study of their non-covalent interactions with various counterparts revealed interesting new results, leading to both methodological and application related progress. The first project of this thesis concentrated on the in-depth analysis of the peptide receptor CBS-Lys-Lys-Phe-NH2 to acquire a better understanding of its binding mode upon complexation with a substrate. In this context it was possible to develop—in cooperation with the group of Prof. Sebastian Schlücker—a direct and label free spectroscopic detection of immobilized compounds which are often found in combinatorial libraries. This new screening method utilizes the advantages of the surface enhanced Raman spectroscopy and allowed for the first time a surface mapping of a single polystyrene bead for the identification of peptides in femtomolar concentrations. Hence, this method allows a very fast and sensitive detection of resin bound compounds. The development of this promising new approach set the starting point for future experiments to enable on-bead library screenings and to investigate the complex formation of immobilized compounds. After the comprehensive analysis of the basic structural features of small peptide receptors in the first part of this thesis, the second big block focused on its in vitro evaluation using biological relevant targets. Therefore, several different modifications of the initial peptide structures were synthesized. These modifications provided a molecular toolkit for the tailor made synthesis of structures individually designed for the respective target. The first tests addressed the interaction with Alzheimer’s related amyloid fibrils. During these experiments, the successful SPPS syntheses of tri- and tetravalent systems were achieved. The comparison of the multivalent form with the corresponding monovalent version was then under special investigations. These concentrated mainly on the interaction with various bacteria strains, as well as with different parasites. To localize the compounds within the organisms, the synthesis of fluorescence labelled versions was achieved. In addition, several compounds were tested by the Institute for Molecular Infection Biology of the University of Würzburg for their antibacterial activity. This thorough evaluation of the biological activity generated precious information about the influence of small structural changes in the peptide receptors. Especially the distinct influence of the multivalency effect and the acquired synthetic skills led to the development of an advanced non-covalent recognition event, as described in the final project of this thesis. The last part of this thesis discussed the development of a novel inhibitor for the serine protease beta-tryptase based on a tailor-made surface recognition event. It was possible to study and analyze the complex interaction with the unique structure of tryptase, that features a tetrameric frame and four catalytic cleavage sites buried deep inside of the hollow structure. However, the point of attack were not the four binding pockets, as mostly described in the literature, but rather the acidic areas around the cleavage sites and at the two circular openings. These should attract peptides with basic residues, which then can block the accessibility to the active sites. A combinatorial library of 216 tetravalent peptide compounds was synthesized to find the best structural composition for the non-covalent inhibition of beta-tryptase. For the screening of the library a new on-bead assay was applied. With this method a simultaneous readout of the total inhibition of all library members was possible, thus allowing a fast and direct investigation of the still resin bound inhibitors. Several additional experiments in solution unveiled the kinetics of the inhibition process. In conclusion, both mono- and multivalent inhibitors interact in a non-destructive and reversible way with the tryptase.
In the generalized Nash equilibrium problem not only the cost function of a player depends on the rival players' decisions, but also his constraints. This thesis presents different iterative methods for the numerical computation of a generalized Nash equilibrium, some of them globally, others locally superlinearly convergent. These methods are based on either reformulations of the generalized Nash equilibrium problem as an optimization problem, or on a fixed point formulation. The key tool for these reformulations is the Nikaido-Isoda function. Numerical results for various problem from the literature are given.
In this work, a behavioural analysis of different mutants of the fruit fly Drosophila melanogaster has been carried out. Primarily, the gap climbing behaviour (Pick & Strauss, 2005) has been assayed as it lends itself for the investigation of decision making processes and the neuronal basis of adaptive behaviour. Furthermore it shows how basic motor actions can be combined into a complex motor behaviour. Thanks to the neurogenetic methods, Drosophila melanogaster has become an ideal study object for neurobiological questions. Two different modules of climbing control have been examined in detail. For the decision making, the mutant climbing sisyphus was analysed. While wild-type flies adapt the initiation of climbing behaviour to the width of the gap and the probability for a successful transition. climbing sisyphus flies initiate climbing behaviour even at clearly insurmountable gap widths. The climbing success itself is not improved in comparison to the wild-type siblings. The mutant climbing sisyphus is a rare example of a hyperactive mutant besides many mutants that show a reduced activity. Basic capabilities in vision have been tested in an optomotor and a distance-estimation paradigm. Since they are not affected, a defect in decision making is most probably the cause of this behavioural aberration. A second module of climbing control is keeping up orientation towards the opposite side of the gap during the execution of climbing behaviour. Mutants with a structural defect in the protocerebral bridge show abnormal climbing behaviour. During the climbing attempt, the longitudinal body axis does not necessarily point into the direction of the opposite side. Instead, many climbing events are initiated at the side edge of the walking block into the void and have no chance to ever succeed. The analysed mutants are not blind. In one of the mutants, tay bridge1 (tay1) a partial rescue attempt used to map the function in the brain succeeded such that the state of the bridge was restored. That way, a visual targeting mechanism has been activated, allowing the flies to target the opposite side. When the visibility of the opposing side was reduced, the rescued flies went back to a tay1 level of directional scatter. The results are in accord with the idea that the bridge is a central constituent of the visual targeting mechanism. The tay1 mutant was also analysed in other behavioural paradigms. A reduction in walking speed and walking activity in this mutant could be rescued by the expression of UAS-tay under the control of the 007Y-GAL4 driver line, which concomitantly restores the structure of the protocerebral bridge. The separation of bridge functions from functions of other parts of the brain of tay1 was accomplished by rescuing the reduced optomotor compensation in tay1 by the mb247-GAL4>UAS-tay driver. While still having a tay1-like protocerebral bridge, mb247-GAL4 rescue flies are able to compensate at wild-type levels. An intact compensation is not depended on the tay expression in the mushroom bodies, as mushroom body ablated flies with a tay1 background and expression of UAS-tay under the control of mb247-GAL4 show wild-type behaviour as well. The most likely substrate for the function are currently unidentified neurons in the fan-shaped body, that can be stained with 007Y-GAL4 and mb247-GAL4 as well.
The present approach highlights a procedural account of intuitive judgments. In intuitions of hidden semantic coherence, people can intuitively detect whether a word triad has a common remote associate (coherent) or not (incoherent) before, and independently from actually retrieving the common associate. The present fluency-affect intuition model (FAIM) maintains that semantic coherence increases the processing fluency for coherent compared to incoherent triads, and that this increased fluency triggers brief and subtle positive affect, which is the experiential basis of these intuitions. Published work concerning 25 experiments is reviewed that gathered empirical support for this model. Furthermore, the impact of fluency and affect was also generalized to intuitions of visual coherence, and intuitions of grammaticality in an artificial grammar learning paradigm.
The genus Borrelia belongs to the spirochete phylum, an ancient evolutionary branch of the domain bacteria that is only afar related to Gram-negative bacteria. Borreliae can be subdivided into the agents of the two borrelian-caused human diseases, Lyme disease and relapsing fever. Both disease patterns are closely related to the peculiar biology of Borrelia species and exhibit a wide spectrum of diverse clinical manifestations. Due to the small 0.91 Mb chromosome, borreliae have a lack of biosynthetic capacity. Thus, all Borrelia species are highly dependent on nutrients provided by their hosts. The transport of nutrients and other molecules across the outer membrane is enabled by pore-forming proteins, so-called porins. Porins are water-filled channels and can be subdivided into two different classes, general diffusion pores and substrate-specific porins. In terms of the Lyme disease agent Borrelia burgdorferi, three putative porins were characterized in previous studies: P13, Oms28 and P66. In contrast to Lyme disease species, the porin knowledge of relapsing fever Borrelia is low, which means that not any porin has actually been described for representatives of these agents. Thus, the general aim of this thesis was to provide insight into the porin content of both, Lyme disease and relapsing fever spirochetes. This aim could be achieved by isolating and identifying porins from Borrelia outer membranes and by biophysically characterizing them in artificial lipid membranes. In one chapter of this study, the first identification and characterization of a relapsing fever porin is presented. The pore-forming protein was isolated from outer membranes of Borrelia duttonii, Borrelia hermsii and Borrelia recurrentis and designated Oms38, for “outer membrane-spanning protein of 38 kDa”. Biophysical characterization of Oms38 was achieved by using the black lipid bilayer method and demonstrated that Oms38 forms small, water-filled channels with a single-channel conductance of 80 pS in 1 M KCl. The Oms38 channel did not exhibit voltage-dependent closure and is slightly selective for anions with a permeability ratio of cations over anions of 0.41 in KCl. Subsequently, a protein homologous to Oms38 was identified in the Lyme disease agents Borrelia burgdorferi, Borrelia garinii and Borrelia afzelii. The pore-forming protein of these species exhibits high sequence homology to Oms38 and similar biophysical properties, i.e. it forms pores of 50 pS in 1 M KCl. Interestingly, titration experiments revealed that this pore could be partly blocked by dicarboxylic anions, which means that this protein does not form a general diffusion pore but a channel with a binding-site specific for those compounds. Consequently, this porin was termed DipA, for “dicarboxylate-specific porin A”. In another set of experiments, it was shown that the porin P66 is present in both Lyme disease and relapsing fever species. Therefor, the outer membranes of the Lyme disease species Borrelia burgdorferi, Borrelia afzelii, Borrelia garinii and the relapsing fever species Borrelia duttonii, Borrelia recurrentis and Borrelia hermsii were closer investigated. Except of the P66 homologue of Borrelia hermsii P66 of all species was highly active in artificial lipid membranes, forming pores with huge single-channel conductances between 9 and 11 nS in 1 M KCl. Moreover, the channel diameter and the constitution of Borrelia burgdorferi P66 were investigated in detail. Therefor, the P66 single-channel conductance in the presence of different nonelectrolytes with known hydrodynamic radii was analyzed in black lipid bilayers. The effective diameter of the P66 channel lumen was determined to be ~1.9 nm. Furthermore, as derived from multi-channel experiments the P66-induced membrane conductance could be blocked by certain nonelectrolytes, such as PEG 400, PEG 600 and maltohexaose. Additional blocking experiments on the single-channel level revealed seven subconducting states and indicated a heptameric constitution of the P66 channel. This indication could be confirmed by Blue native PAGE analysis which demonstrated that P66 units form a complex with a corresponding mass of approximately 440 kDa. Taking together, this thesis describes detailed biochemical and biophysical investigations of both Lyme disease and relapsing fever Borrelia porins and represents an important step forward in understanding the outer membrane pathways for nutrient uptake of these strictly host-dependent, pathogenic spirochetes. Furthermore, it provides some knowledge of the outer-membrane protein composition of Borrelia spirochetes. A profound knowledge of surface-exposed proteins, such as porins, is one precondition for the production of a successful vaccine and the drug design against the two borrelian-caused diseases.
The Upper Bajocian-Bathonian Kashafrud Formation is a thick package of siliciclastic sediments that crops out in NE Iran from the southeast, near the Afghanistan border, to north- northwestern areas around the city of Mashhad. The thickness ranges from less than 300 m in a deltaic succession (Kuh-e-Radar) to more than 2500 m in the Maiamay area, but the normal thickness in Ghal-e-Sangi, Kol-e-Malekabad, and Fraizi areas is about 1200-1300 m. It is the fill of an elongated basin, which extended for more than 200 km in NW-SE direction and a width of at least 50 km along the southern margin of the Koppeh Dagh. Prior to this study, little information existed about the sedimentary environments and other characters, especially the geometry of the basin. Exact biostratigraphic data from the top of the Kashafrud Formation were rare. Based on the macrofauna from the lower part of the overlying Chamanbid Formation the upper boundary of the Kashafrud Formation had been attributed to the Late Bathonian and/or Early Callovian, but now the upper limit of the Kashafrud Formation is defined as Late Bathonian in age, based on ammonite biostratigraphy. Except for chapter one, which deals with the introduction and related sub-titles, in the following chapters, step by step, field observations and data were surveyed according to the questions to solve. In order to reconstruct the facies architecture and the geometry of the basin, a number of sections have been logged in detail (see chapter 3, “The sections”). The exact biostratigraphic setting is discussed in chapter 4 (“Biostratigraphy”). Sedimentary environments range from non-marine alluvial fans and braided rivers in the basal part of the succession to deltas, storm-dominated shelf, slope and deep-marine basin. The latter comprises the largest part of the basin fill, consisting of monotonous mudstones, siltstones and proximal to distal turbidities. The only continuous carbonate unit (~30 m) locally formed at Tappenader. Other localities in which thin fossil-bearing carbonate strata occur are Torbat-e-Jam (benthic fauna) and, to a lesser extent, Ghal-e-Sangi. These rare shallow-water carbonates, which also contain corals, represent only short intervals (see chapter 5,” Facies association and sedimentary environments”). Relative changes in sea level were reconstructed on the basis of deepening- and shallowing-upward trends. Sequence boundaries and parasequences have been distinguished and analyzed in chapter 6 (“Sequence stratigraphy”). In most areas, the basin rapidly evolved from a shallow marine, transgressive succession to a deep-marine, basinal succession. The only area where shallow conditions persisted from the Late Bajocian to the Late Bathonian, and even into the Early Callovian is the Kuh-e-Radar area which corresponds to a fan-delta setting. A trace fossil analysis has been carried out to obtain additional evidence on the bathymetry of the basin (see chapter 7, “Ichnology”). Altogether 29 ichnospecies belonging to 15 ichnogenera have been identified, as well as 10 ichnogenera, which were determined only at genus level. They can be grouped in the well-known “Seilacherian ichnofacies”. Very high subsidence rates and strong lateral thickness variations suggest that the Kashafrud Formation is a rift related basin that formed as the eastern extension of the South Caspian Basin. The basin evolution is reviewed, the eastern and western continuations of the basin were checked in the field and also in the literature (see chapter 8, “Basin evolution”). In all, the present study provided new insights into the development of the Kashafrud Formation, e.g. more biostratigraphic data from the base and the top of the succession, a relatively complete picture of the trace fossil associations, a better recognition and reconstruction of the sedimentary environments in different parts of the basin. Finally this research project will be a good basis for further investigations, especially towards the west, as parts of the Kashafrud Formation are source rocks of a hydrocarbon reservoir in NE Iran.
This thesis deals with three selected dimensions of strategic behavior, namely investment in R&D, mergers and acquisitions, and inventory decisions in dynamic oligopolies. The question the first essay addresses is how the market structure evolves due to innovative activities when firms' level of technological competence is valuable for more than one project. The focus of the work is the analysis of the effect of learning-by-doing and organizational forgetting in R&D on firms' incentives to innovate. A dynamic step-by-step innovation model with history dependency is developed. Firms can accumulate knowledge by investing in R&D. As a benchmark without knowledge accumulation it is shown that relaxing the usual assumption of imposed imitation yields additional strategic effects. Therefore, the leader's R&D effort increases with the gap as she is trying to avoid competition in the future. When firms gain experience by performing R&D, the resulting effect of knowledge induces technological leaders to rest on their laurels which allows followers to catch up. Contrary to the benchmark case the leader's innovation effort declines with the lead. This causes an equilibrium where the incentives to innovate are highest when competition is most intense. Using a model of oligopoly in general equilibrium the second essay analyzes the integration of economies that might be accompanied by cross-border merger waves. Studying economies which prior to trade were in stable equilibrium where mergers were not profitable, we show that globalization can trigger cross-border merger waves for a sufficiently large heterogeneity in marginal cost. In partial equilibrium, consumers benefit from integration even when a merger wave is triggered which considerably lowers intensity of competition. Welfare increases. In contrast, in general equilibrium where interactions between markets and therefore effects on factor prices are considered, gains from trade can only be realized by reallocation of resources. The higher the technological dissimilarity between countries the better can efficiency gains be realized in integrated general equilibrium. The overall welfare effect of integration is positive when all firms remain active but indeterminate when firms exit or are absorbed due to a merger wave. It is possible for decreasing competition to dominate the welfare gain from more efficient resource allocation across sectors. Allowing for firms' entry alters results as in an integrated world coexistence of firms of different countries is never possible. Comparative advantages with respect to entry and production are important for realizing efficiency gains from trade. The third essay analyzes the interaction between price and inventory decisions in an oligopoly industry and its implications for the dynamics of prices. The work extends existing literature and especially the work of Hall and Rust (2007) to endogenous prices and strategic oligopoly competition. We show that the optimal decision rule is an (S,s) order policy and prices and inventories are strategic substitutes. Fixed ordering costs generate infrequent orders. Additionally, with strategic competition in prices, (S,s) inventory behavior together with demand uncertainty generates cyclical pattern in prices The last chapter presents some concluding remarks on the results of the essays.
We consider competitive location problems where two competing providers place their facilities sequentially and users can decide between the competitors. We assume that both competitors act non-cooperatively and aim at maximizing their own benefits. We investigate the complexity and approximability of such problems on graphs, in particular on simple graph classes such as trees and paths. We also develop fast algorithms for single competitive location problems where each provider places a single facilty. Voting location, in contrast, aims at identifying locations that meet social criteria. The provider wants to satisfy the users (customers) of the facility to be opened. In general, there is no location that is favored by all users. Therefore, a satisfactory compromise has to be found. To this end, criteria arising from voting theory are considered. The solution of the location problem is understood as the winner of a virtual election among the users of the facilities, in which the potential locations play the role of the candidates and the users represent the voters. Competitive and voting location problems turn out to be closely related.
The Three-Site Higgsless Model is alternative implementation of electroweak symmetry breaking which in the Standard Model is mediated by the Higgs mechanism. The main features of this model is the appearance of two new heavy vector resonances W' and Z' with masses > 380 GeV as well as a set of new heavy fermions (> 1.8 TeV). In this model, unitarity of the amplitudes for the scattering of longitudinal gauge bosons is maintained by the exchange of the W' and Z' up to a scale of ~2 TeV. Consistency with the electroweak precision observables from the LEP / LEP-II experiments implies an exceedingly small coupling of the new vector bosons to the light Standard Model fermions (about 3% of the isospin gauge coupling). In this thesis, the LHC phenomenology of this scenario is explored. To this end, we calculated the couplings and widths of all the new particles and implemented the model into the Monte-Carlo eventgenerator WHIZARD / O'Mega. With this implementation, we simulated the parton-level production of the gauge boson and fermion partners in different channels possibly suitable for their discovery at the LHC. The results are presented together with an introduction to the model and a discussion of its properties. We find that, while the fermiophobic nature of the new heavy gauge bosons does make them intrinsically difficult to observe at a collider, the LHC should be able to establish the existence of both resonances and even give some hints about the properties of their couplings which would be a vital test of the consistency of such a scenario. For the heavy fermions, we find that their large mass is accompanied by relative widths of more than $10\%$, making them ill-suited for a direct discovery at the LHC. Nevertheless, our simulations reveal that there is a part of parameter space where, given enough time, patience and a good understanding of detector and backgrounds, a direct discovery might be possible.
Evaluation of 1H-NMR and GC/MS-based metabonomics for the assessment of liver and kidney toxicity
(2009)
For the assessment of metabonomics techniques for the early, non-invasive detection of toxicity, the nephrotoxins gentamicin (s.c. administration of 0, 60 and 120 mg/kg bw 2x daily for 8 days), ochratoxin A (p.o. administration of 0, 21, 70 and 210 µg/kg bw 5 days/week for 90 days) and aristolochic acid (p.o. administration of 0, 0.1, 1.0 and 10 mg/kg bw for 12 days) were administered to rats and urine samples were analyzed with 1H-NMR and GC/MS. Urine samples from the InnoMed PredTox project were analyzed as well, thereby focusing on 1H-NMR analysis and bile duct necrosis as histopathological endpoint. 1H-NMR analysis used water supression with the following protocol: 1 M phosphate buffer, D2O as shift lock reagent, D4-trimethylsilylpropionic acid as chemical shift reference, noesygppr1d pulse sequence (Bruker). For multivariate data analysis, spectral intensity was binned into 0.04 ppm wide bins. GC/MS analysis of urine was carried out after protein precipitation with methanol, drying, derivatization with methoxyamine hydrochloride in pyridine and with methyl(trimethylsilyl)trifluoroacetamide on a DB5-MS column using EI ionization. The chromatograms were prepared for multivariate data analysis using the R-program based peak picking and alignment software XCMS version 2.4.0. Principal component analysis (PCA) to detect and visualize time-point and dose-dependent differences between treated animals and controls and orthogonal projection to latent structures discriminant analysis (OPLS-DA) for identification of potential molecular markers of toxicity was carried out using SIMCA P+ 11.5 1H-NMR-based markers were identified and quantified with the Chenomx NMR Suite, GC/MS based markers were identified using the NIST Mass Spectral Database and by co-elution with authentic reference standards. PCA of urinary metabolite profiles was able to differentiate treated animals from controls at the same time as histopathology. An advantage over classical clinical chemistry parameters regarding sensitivity could be observed in some cases. Metabonomic analysis with GC/MS and 1H-NMR revealed alterations in the urinary profile of treated animals 1 day after start of treatment with gentamicin, correlating with changes in clinical chemistry parameters and histopathology. Decreased urinary excretion of citrate, 2-oxoglutarate, hippurate, trigonelline and 3-indoxylsulfate increased excretion of 5-oxoproline, lactate, alanine and glucose were observed. Ochratoxin A treatment caused decreased excretion of citrate, 2-oxoglutarate and hippurate and and increased excretion of glucose, myo-inositol, N,N-dimethylglycine, glycine, alanine and lactate as early as 2 weeks after start of treatment with 210µg OTA/kg bw, correlating with changes in clinical chemistry parameters and histopathology. Integration of histopathology scores increased confidence in the molecular markers discovered. Aristolochic acid treatment resulted in decreased urinary excretion of citrate, 2-oxoglutarate, hippurate and creatinine as well as increased excretion of 5-oxoproline, N,N-dimethylglycine, pseudouridine and uric acid. No alterations in clinical chemistry parameters or histopathology were noted.Decreased excretion of hippurate indicates alterations in the gut microflora, an effect that is expected as pharmacological action of the aminoglycoside antibiotic gentamicin and that can also be explained by the p.o. administration of xenobiotica. Decreased Krebs cycle intermediates (citrate and 2-oxoglutarate) and increased lactate is associated with altered energy metabolism. Increased pseudouridine excretion is associated with cell proliferation and was observed with aristolochic acid and ochratoxin A, for which proliferative processes were observed with histopathology. 5-oxoproline and N,N-dimethylglycine can be associated with oxidative stress. Glucose, a marker of renal damage in clinical chemistry, was observed for all three nephrotoxins studied. Single study analysis with PCA of GC/MS chromatograms and 1H-NMR spectra of urine from 3 studies conducted within the InnoMed PredTox project showing bile duct necrosis revealed alterations in urinary profiles with the onset of changes in clinical chemistry and histopathology. Alterations were mainly decreased Krebs cycle intermediates and changes in the aromatic gut flora metabolites, an effect that may result as a secondary effect from altered bile flow. In conclusion, metabonomics techniques are able to detect toxic lesions at the same time as histopathology and clinical chemistry. The metabolites found to be altered are common to most toxicities and are not organ-specific. A mechanistic link to the observed toxicity has to be established in order to avoid confounders such as body weight loss, pharmacological effects etc. For pattern recognition purposes, large databases are necessary.
The spectroscopic properties of molecular aggregates have been investigated by means of quantum dynamical calculations. Thereby both linear and nonlinear spectroscopic techniques have been taken into account. For the simulation of absorption and CD-spectra, coupling effects were regarded as well as the relative orientation of the monomer units in order to determine the parameters by reproducing measured spectra. For a more detailled description, results from quantum chemical calculations have also been included. Furthermore, investigations on nonlinear spectroscopy of molecular dimers have been performed.
The bidirectional influence of parenchymal cells and cells of the immune system, especially of antigen-presenting and CD8\(^+\) T cells, in situations of putative auto- immune pathogenicity and degeneration was the main topic of this thesis. In the first part, the influence of human muscle cells on antigen-presenting cells was investigated. In inflammatory myopathies prominent infiltrates of immune cells containing T cells and antigen-presenting cells like macrophages and dendritic cells are present. The hypothesis was that human myoblasts have an inhibiting influence on these antigen-presenting cells under homeostatic conditions. A dysfunction or impairment under inflammatory circumstances might contribute to the development of myopathic conditions. The surface analysis of dendritic cells cocultured with myoblasts showed that immature dendritic cells could be driven into a reversible semi- mature state with significantly elevated levels of CD80. These dendritic cells were additionally characterized by their inhibiting function on T-cell proliferation. It was also shown that the lysates of healthy myoblasts could strongly enhance the phagocytic ability of macrophages, which could help with muscle regeneration and which might be disturbed in myositis patients. The second part of this thesis was about the clonal specificity of CD8\(^+\) T cells in a mouse model with genetically induced over-expression of PLP in oligodendrocytes. Here, we could show that the cytotoxic T lymphocytes, which had previously been shown to be pathogenic, were clonally expanded in the CNS of the transgenic mice. The amino acid sequences of the corresponding receptor chains were not identical, yet showed some similarities, which could mean that these clones recognize similar antigens (or epitopes of the same antigen). The knockout of PD-1 in this setting allowed for an analysis of the importance of tissue immune regulation. It became evident that the absence of PD-1 induced a larger number of clonal expansions in the CNS, hinting towards a reduced threshold for clonal disturbance and activation in these T cells. The expansions were, however, not pathogenic by themselves. Only in the presence of tissue damage and an antigenic stimulus (in our case the overexpression of PLP), the PD-1 limitation exacerbated the immune pathogenicity. Therefore, only in the presence of a “tissue damage signal”, the dyshomeostasis of T cells lacking PD-1 achieved high pathogenetic relevance. Finally, we investigated the pathogenetic role of CD8 T cells in Rasmussen encephalitis, a rare and chronic neurological disease mainly affecting children. The analysis of the T-cell receptor repertoire in Rasmussen encephalitis patients in the peripheral CD4\(^+\) and CD8\(^+\) T-cell compartments as well as the brain revealed the involvement of T cells in the pathogenicity of this disease. Many clonal expansions in the brain matched CD8\(^+\) T-cell expansions in the periphery on the sequence level. These putatively pathogenic clones could be visualized by immunohistochemistry in the brain and were found in close proximity to astrocytes and neurons. Additionally, the expanded clones could be found in the periphery of patients for at least one year.
In the context of the indirect search for non-standard physics in the flavour sector of the Standard Model (SM), one of the most interesting processes is the rare inclusive B -> X_s gamma decay. On the one hand, being a flavour-changing neutral current, this B decay is sensitive to new physics, as it is loop-suppressed in the SM. On the other hand, it is only mildly affected by non-perturbative effects, and thus allows for precise theoretical predictions in the framework of renormalization-group improved perturbation theory. Accurate measurements as well as precise theoretical predictions with a good control over both perturbative and non-perturbative contributions have to be provided in order to derive stringent constraints on the parameter space of physics beyond the SM. On the experimental side, an outstanding accuracy in the measurement of the B -> Xs gamma decay rate has been achieved, which is mainly due the specialized experiments BaBar and Belle at the so-called B factories. To match the small experimental uncertainty, higher order computations within an effective low-energy theory of the SM are mandatory. In fact, next-to-next-to-leading order (NNLO) QCD corrections are required to provide a prediction for the decay rate with the same precision as the measurement. The NNLO evaluation of the B -> Xs gamma decay rate has been pursued by various groups over the last decade. The project was completed to a large extent and a first estimate at this level of perturbation theory was obtained in 2006. This prediction, however, lacks important contributions from yet unknown matrix elements, that were estimated from results which are only partially known to date. In this work, we provide a framework for the systematic study of the missing matrix elements at the NNLO. As main results of this thesis, we determine fermionic corrections to the charm quark mass dependent matrix elements of four-quark operators in the effective theory at NNLO. For the first time, the full mass dependence was kept. Moreover, we evaluate both bosonic and fermionic corrections to the decay rate in the limit of vanishing charm quark mass. These findings, combined with yet unknown remaining real contributions, will help to reduce the uncertainty of the NNLO branching ratio estimate considerably. Another central topic of the present work is the development of an automatic high-precision computation of multi-loop multi-scale integrals, a crucial ingredient for the here presented results.
trans-1,1,1,3-Tetrafluoropropene (HFO-1234ze) and 2,3,3,3-tetrafluoropropene (HFO-1234yf) are non-ozone-depleting fluorocarbon replacements with low global warming potentials and short atmospheric lifetimes. They are developed as foam blowing agent and refrigerant, respectively. Investigations on biotransformation in different test species and in vitro systems are required to assess possible health risks of human exposure and needed for commercial development. The biotransformation of HFO-1234ze and HFO-1234yf was therefore investigated after inhalation exposure. Male Sprague-Dawley rats were exposed to air containing 2 000; 10,000; or 50,000 ppm (n=5/concentration) HFO-1234ze or HFO-1234yf. Male B6C3F1 mice were only exposed to 50,000 ppm HFO-1234ze or HFO-1234yf. Due to lethality observed in a developmental study with rabbits after exposure to high concentrations of HFO-1234yf, the metabolic fate of the compound was tested by whole body inhalation exposure of female New Zealand White rabbits to air containing 2 000; 10,000; or 50,000 ppm (n=3/concentration) HFO-1234yf. All inhalation exposures were conducted for 6 h in a dynamic exposure chamber. After the end of the exposures, animals were individually housed in metabolic cages and urines were collected at 6 or 12 h intervals for 48 h (rats and mice) or 60 h (rabbits). For metabolite identification, urine samples were analyzed by 1H-coupled and 1H-decoupled 19F-NMR and by LC/MS-MS or GC/MS. Metabolites were identified by 19F-NMR chemical shifts, signal multiplicity, 1H-19F coupling constants and by comparison with synthetic reference compounds. Biotransformation of HFO-1234ze in rats exposed to 50,000 ppm yielded S-(3,3,3-trifluoro-trans-propenyl)mercaptolactic acid as the predominant metabolite which accounted for 66% of all integrated 19F-NMR signals in urines. No 19F-NMR signals were found in spectra of rat urine samples collected after inhalation exposure to 2 000 or 10,000 ppm HFO-1234ze likely due to insufficient sensitivity. S-(3,3,3-Trifluoro-trans-propenyl)-L-cysteine, N-acetyl-S-(3,3,3-trifluoro-trans-propenyl)-L-cysteine, 3,3,3-trifluoropropionic acid and 3,3,3-trifluorolactic acid were also present as metabolites in urine samples of rats and mice at the 50,000 ppm level. A presumed amino acid conjugate of 3,3,3-trifluoropropionic acid was the major metabolite of HFO-1234ze in urine samples of mice exposed to 50,000 ppm and related to 18% of total integrated 19F-NMR signals. Quantitation of three metabolites in urines of rats and mice was performed, using LC/MS-MS or GC/MS. The quantified amounts of the metabolites excreted with urine in both mice and rats, suggest only a low extent (<<1% of dose received) of biotransformation of HFO-1234ze and 95% of all metabolites were excreted within 18 h after the end of the exposures (t1/2 approx. 6 h). Due to its low boiling point of −22 °C, most of the inhaled HFO-1234ze is expected to be readily exhaled. Moreover, steric and electronic factors may decrease the reactivity of the parent compound with soft nucleophiles such as glutathione. The obtained results suggest that HFO-1234ze is subjected to an addition-elimination reaction with glutathione and to a cytochrome P450-mediated epoxidation at low rates. The extent of a direct addition reaction of HFO-1234ze with glutathione is negligible, compared to that of the observed addition-elimination reaction. The results of in vivo testing of HFO-1234ze could not be supported by in vitro investigations, since HFO-1234ze was not metabolized in incubations with either liver microsomes or subcellular fractions from rat and human. Regarding the structures delineated in the biotransformation scheme of HFO-1234ze, 1,1,1,3-tetrafluoroepoxypropane and 3,3,3-trifluoropropionic acid are toxic intermediates which, however, are not supposed to display toxicity in the species after exposure to HFO-1234ze, due to the low extent of formation and an efficient detoxification of the epoxide by hydrolysis and glutathione conjugation. The findings of biotransformation of HFO-1234ze in rats and mice correlate with the absence of adverse effects in the toxicity testings and indicate their innocuousness to a human exposure. Biotransformation of HFO-1234yf yielded N-acetyl-S-(3,3,3-trifluoro-2-hydroxypropanyl)-L-cysteine as predominat metabolite which accounted for approx. 44, 90 and 32% (50,000 ppm) of total 19F-NMR signal intensities in urine samples from rabbits, rats and mice, respectively. S-(3,3,3-Trifluoro-2-hydroxypropanyl)mercaptolactic acid and the sulfoxides of mercapturic acid and mercaptolactic acid S-conjugate were identified as minor metabolites of HFO-1234yf in urine samples from rabbits, rats and mice, whereas trifluoroacetic acid, 3,3,3-trifluorolactic acid and 3,3,3-trifluoro-1-hydroxyacetone were present as minor metabolites only in urine samples from rats and mice. The absence of these metabolites in rabbit urine samples...
This thesis analyzes the 2001-2006 labor market reforms in Germany. The aim of this work is twofold. First, an overview of the most important reform measures and the intended effects is given. Second, two specific and very fundamental amendments, namely the merging of unemployment assistance and social benefits, as well as changes in the duration of unemployment insurance benefits, are analyzed in detail to evaluate their effects on individuals and the entire economy. Using a matching model with optimal search intensity and Semi-Markov methods, the effects of these two amendments on the duration of unemployment, optimal search intensity and unemployment are analyzed.
Mediators of Social Anxiety - External Social Threat-Cues vs. Self-Related Negative Cognitions
(2009)
Based on a review of models and empirical findings a working model is proposed, suggesting that self-related negative cognitions and biased processing of external social threat-cues are mediators of social anxiety. Hypotheses derived from this model were tested in three experiments. The first experiment examined whether levels of trait social anxiousness predicted fearful responding to external social threat-cues (angry vs. neutral and happy facial expressions) during social evaluation. Higher trait social anxiousness predisposes to an inward focus on one’s fear reaction to social threat. Using this strategy was expected to enhance fearful responding to angry facial expressions. A strategy of identifying with angry faces was expected to counteract fearful responding, but was expected to fail more often with increasing levels of trait social anxiousness. To examine these hypotheses, affective modulation of the startle eye-blink was assessed in forty-four undergraduate students. This measure served as a probe into the activation of brain structures involved in the automatic evaluation of environmental threat-cues. Trait and state anxiety as well as explicit emotional responding to the stimuli were assessed with questionnaires and ratings. Processing angry faces potentiated startle amplitudes as expected. Low arousal induced by the stimuli was a probable reason, why startle potentiation to happy faces emerged instead of attenuation. Trait social anxiousness and the cognitive strategies did not influence these effects. Yet, increased trait social anxiousness predicted decreased startle latency, indicating motor hyper-responsivity, which is part of the clinical representation of social anxiety disorder (SAD). Processing facial expressions and identifying with them disrupted this association. Previous studies support that similar strategies may enhance treatment of SAD. Individuals with SAD were expected to respond with increased arousal to external social threat-cues. Therefore, the second experiment examined whether nine individuals with SAD showed attentional (prepulse inhibition, PPI) or affective startle modulation to angry as compared to neutral and happy facial expressions. Corrugator supercilii activity was assessed as a behavioral indicator for effects of facial expressions. The remaining setup resembled the first experiment. Facial expressions did not modulate the startle reflex, but corrugator supercilii activity was sensitive to facial valence. However, the effects were not related to trait social anxiousness. Apparently, angry facial expressions do not act as phobic stimuli for individuals with SAD. The third experiment examined whether focusing on self-related negative cognitions or biased processing of external social threat-cues mediates relationships between trait social anxiety and anxious responding in a socially challenging situation. Inducing self-related negative cognitions vs. relaxation was expected to reveal a functional dependency on the supposed mediation in a multivariate assessment of criteria of the working model. Within this design, the impact of external social threat-cues (facial expressions and emotional words) was compared to control stimuli and context effects, using the startle paradigm. The findings provide first evidence for full statistical mediation of the associations between trait social anxiety and self-reported anxiety as well as parasympathetic withdrawal by self-related negative cognitions, when thirty-six undergraduate students anticipated public speaking. Apprehensive arousal, as indicated by increased skin conductance levels and heart rate, was present in all participants. Observer ratings of behavior during public speaking matched the self-rated quality of the performance. None of these measures were correlated with trait social anxiousness. Startle amplitude correlated with state and trait social anxiety, but was no mediator. Finally, there was no affective modulation of the startle amplitude by external social threat-cues. These studies advance both our current understanding of the factors that mediate social anxiety responses to situations and our knowledge of the physiological and anatomical mechanisms involved in social anxiety. Based on these findings a revised version of the working model on mediators of social anxiety is proposed in the hope it may aid further research for the ultimate goal of developing an empirically validated functional anatomical model of social anxiety.
Photosynthesis is the most fundamental process of life on earth. The biological production of oxygen in plant photosynthesis occurs in photosystem II (PSII). Here two water molecules are coupled in a four-electron oxidation to one O2 molecule, catalyzed by a tetranuclear manganese complex, known as the oxygen-evolving complex (OEC). In this thesis, density-functional theory (DFT) methods were validated and subsequently employed to study structures, spin-density distributions and EPR parameters of mono-, di-, and tetranuclear complexes with regard to the OEC. The goal was to draw conclusions on the molecular and electronic structure of the OEC.