Funktion der Phospholipase D2 bei der Desensibilisierung und Internalisierung des [my]-Opioidrezeptors

[My]-Opioidrezeptor, Endozytose, Phospholipase D2, Desensitisierung, Resensitisierung, Internalisierung

Synthese des Dioxabicyclooctanfragmentes der Sorangicine und Studien zur Konstruktion des E,Z,Z-Triensystems

Magdeburg, Univ., Fak. für Verfahrens- und Systemtechnik, Diss., 2011

Entwicklung einer Anwendung zur Steuerung der Stapelverarbeitungsfunktionen in Abaqus

[s.c.]

Kungl. Svenska vetenskapsakademiens handlingar.

n.f.:bd.3 (1859-1860)

Kungl. Svenska vetenskapsakademiens handlingar.

n.f.:bd.1 (1855-1856)

Resource-monotonicity for house allocation problems

We study a simple model of assigning indivisible objects (e.g., houses, jobs, offices, etc.) to agents. Each agent receives at most one object and monetary compensations are not possible. We completely describe all rules satisfying efficiency and resource-monotonicity. The characterized rules assign the objects in a sequence of steps such that at each step there is either a dictator or two agents "trade" objects from their hierarchically specified "endowments."

Efficient priority rules

We study the assignment of indivisible objects with quotas (houses, jobs, or offices) to a set of agents (students, job applicants, or professors). Each agent receives at most one object and monetary compensations are not possible. We characterize efficient priority rules by efficiency, strategy-proofness, and renegotiation-proofness. Such a rule respects an acyclical priority structure and the allocations can be determined using the deferred acceptance algorithm.

Free triples, large indifference classes and the majority rule

We present a new domain of preferences under which the majority relation is always quasi-transitive and thus Condorcet winners always exist. We model situations where a set of individuals must choose one individual in the group. Agents are connected through some relationship that can be interpreted as expressing neighborhood, and which is formalized by a graph. Our restriction on preferences is as follows: each agent can freely rank his immediate neighbors, but then he is indifferent between each neighbor and all other agents that this neighbor "leads to". Hence, agents can be highly perceptive regarding their neighbors, while being insensitive to the differences between these and other agents which are further removed from them. We show quasi-transitivity of the majority relation when the graph expressing the neighborhood relation is a tree. We also discuss a further restriction allowing to extend the result for more general graphs. Finally, we compare the proposed restriction with others in the literature, to conclude that it is independent of any previously discussed domain restriction.

Gehring-Hayman theorem for conformal deformations

We study conformal deformations of a uniform space that satisfies the Ahlfors Q-regularity condition on balls of Whitney type. We verify the Gehring–Hayman Theorem by using a Whitney Covering of the space.

Trypanosomes of some Fennoscandian birds

Linear measurements and derived indices of trypanosomes from species of Fennoscandian birds were compared to those reported form Trypanosoma avium, T. everetti, T. ontarioensis and T. paddae. The trypanosomes encountered in the Fennoscandian birds were identified as T. avium from Tengmalm's owl Aegolius funereus and the pied flycatcher Ficedula hypoleuca, T. everetti from the great tit Parus major and collared flycatcher F. albicollis and T. ontarioensis from the collared flycatcher; T. paddae was not seen.

IL-5 and IL-5 receptor in asthma

Eosinophils, along with mast cells are key cells involved in the innate immune response against parasitic infection whereas the adaptive immune response is largely dependent on lymphocytes. In chronic parasitic disease and in chronic allergic disease, IL-5 is predominantly a T cell derived cytokine which is particularly important for the terminal differentiation, activation and survival of committed eosinophil precursors. The human IL-5 gene is located on chromosome 5 in a gene cluster that contains the evolutionary related IL-4 family of cytokine genes. The human IL-5 receptor complex is a heterodimer consisting of a unique a subunit (predominantly expressed on eosinophils) and a beta subunit which is shared between the receptors for IL-3 & GM-CSF (more widely expressed). The a subunit is required for ligand-specific binding whereas association with the beta subunit results in increased binding affinity. The alternative splicing of the alphaIL-5R gene which contains 14 exons can yield several alphaIL-5R isoforms including a membrane-anchored isoform (alphaIL-5Rm) and a soluble isoform (alphaIL-5Rs). Cytokines such as IL-5 produce specific and non-specific cellular responses through specific cell membrane receptor mediated activation of intracellular signal transduction pathways which, to a large part, regulate gene expression. The major intracellular signal transduction mechanism is activation of non-receptor associated tyrosine kinases including JAK and MAP kinases which can then transduce signals via a novel family of transcriptional factors named signal transducers and activators of transcription (STATS). JAK2, STAT1 and STAT 5 appear to be particularly important in IL-5 mediated eosinophil responses. Asthma is characterized by episodic airways obstruction, increased bronchial responsiveness, and airway inflammation. Several studies have shown an association between the number of activated T cells and eosinophils in the airways and abnormalities in FEV1, airway reactivity and clinical severity in asthma. It has now been well documented that IL-5 is highly expressed in the bronchial mucosa of atopic and intrinsic asthmatics and that the increased IL-5 mRNA present in airway tissues is predominantly T cell derived. Immunocytochemical staining of bronchial biopsy sections has confirmed that IL-5 mRNA transcripts are translated into protein in asthmatic subjects. Furthermore, the number of activated CD 4 + T cells and IL-5 mRNA positive cells are increased in asthmatic airways following antigen challenge and studies that have examined IL-5 expression in asthmatic subjects before and after steroids have shown significantly decreased expression following oral corticosteroid treatment in steroid-sensitive asthma but not in steroid resistant and chronic severe steroid dependent asthma. The link between T cell derived IL-5 and eosinophil activation in asthmatic airways is further strengthened by the demonstration that there is an increased number of alphaIL-5R mRNA positive cells in the bronchial biopsies of atopic and non-atopic asthmatic subjects and that the eosinophil is the predominant site of this increased alphaIL-5R mRNA expression. We have also shown that the subset of activated eosinophils that expressed mRNA for membrane bound alpha IL5r inversely correlated with FEV1, whereas the subset of activated eosinophils that expressed mRNA for soluble alphaIL5r directly correlated with FEV1. Hence, not only does this data suggest that the presence of eosinophils expressing alphaIL-5R mRNA contribute towards the pathogenesis of bronchial asthma, but also that the eosinophil phenotype with respect to alphaIL-5R isoform expression is of central importance. Finally, there are several animal, and more recently in vitro lung explant, models of allergen induced eosinophilia, late airway responses(LARS), and bronchial hyperresponsiveness(BHR) - all of which support a link between IL-5 and airway eosinophila and bronchial hyperresponsiveness. The most direct demonstration of T cell involvement in LARS is the finding that these physiological responses can be transferred by CD4+ but not CD8+ T cells in rats. The importance of IL-5 in animal models of allergen induced bronchial hyperresponsiveness has been further demonstrated by a number of studies which have indicated that IL-5 administration is able to induce late phase responses and BHR and that anti-IL-5 antibody can block allergen induced late phase responses and BHR. In summary, activated T lymphocytes, IL5 production and eosinophil activation are particularly important in the asthmatic response. Human studies in asthma and studies in allergic animal models have clearly emphasised the unique role of IL-5 in linking T lymphocytes and adaptive immunity, the eosinophil effector cell, and the asthma phenotype. The central role of activated lymphocytes and eosinophils in asthma would argue for the likely therapeutic success of strategies to block T cell and eosinophil activation (eg steroids). Importantly, more targeted therapies may avoid the complications associated with steroids. Such therapies could target key T cell activation proteins and cytokines by various means including blocking antibodies (eg anti-CD4, anti-CD40, anti-IL-5 etc), antisense oligonucleotides to their specific mRNAs, and/or selective inhibition of the promoter sites for these genes. Another option would be to target key eosinophil activation mechanisms including the aIL5r. As always, the risk to benefit ratio of such strategies await the results of well conducted clinical trials.

Control of optical fields and single photon emitters by advanced nanoantenna structures

The control of optical fields on the nanometre scale is becoming an increasingly important tool in many fields, ranging from channelling light delivery in photovoltaics and light emitting diodes to increasing the sensitivity of chemical sensors to single molecule levels. The ability to design and manipulate light fields with specific frequency and space characteristics is explored in this project. We present an alternative realisation of Extraordinary Optical Transmission (EOT) that requires only a single aperture and a coupled waveguide. We show how this waveguide-resonant EOT improves the transmissivity of single apertures. An important technique in imaging is Near-Field Scanning Optical Microscopy (NSOM); we show how waveguide-resonant EOT and the novel probe design assist in improving the efficiency of NSOM probes by two orders of magnitude, and allow the imaging of single molecules with an optical resolution of as good as 50 nm. We show how optical antennas are fabricated into the apex of sharp tips and can be used in a near-field configuration.

A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p≤5×10−7). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10−8) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2×10−8) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5×10−8; rs1229984-ADH1B, p = 7×10−9; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.