Periodic twisted cohomology and T-duality

The initial motivation of this work was to give a topological interpretation of two-periodic twisted de-Rham cohomology which is generalizable to arbitrary coefficients. To this end we develop a sheaf theory in the context of locally compact topological stacks with emphasis on the construction of the sheaf theory operations in unbounded derived categories, elements of Verdier duality and integration. The main result is the construction of a functorial periodization functor associated to a U(1)-gerbe. As applications we verify the $T$-duality isomorphism in periodic twisted cohomology and in periodic twisted orbispace cohomology.Comment: 128 pages; v2: small corrections (e.g. of typos), version to appear in Asterisqu

Inertia and delocalized twisted cohomology

We show that the inertia stack of a topological stack is again a topological stack. We further observe that the inertia stack of an orbispace is again an orbispace. We show how a U(1)-banded gerbe over an orbispace gives rise to a flat line bundle over its inertia stack. Via sheaf theory over topological stacks it gives rise to the twisted delocalized cohomology of the orbispace. With these results and constructions we generalize concepts, which are well-known in the smooth framework, to the topological case. In the smooth case we show, that our sheaf-theoretic definition of twisted delocalized cohomology of orbispaces coincides with former definitions using a twisted de Rham complex.Comment: 42 page

Ubiquitination and Ubiquitin-Like Modifications in Multiple Myeloma: Biology and Therapy

Multiple myeloma is a genetically heterogeneous plasma cell malignancy characterized by organ damage and a massive production of (in-)complete monoclonal antibodies. Coping with protein homeostasis and post-translational regulation is therefore essential for multiple myeloma cells to survive. Furthermore, post-translational modifications such as ubiquitination and SUMOylation play key roles in essential pathways in multiple myeloma, including NFκB signaling, epigenetic regulation, as well as DNA damage repair. Drugs modulating the ubiquitin-proteasome system, such as proteasome inhibitors and thalidomide analogs, are approved and highly effective drugs in multiple myeloma. In this review, we focus on ubiquitin and ubiquitin-like modifications in the biology and current developments of new treatments for multiple myeloma

Hyperhidrosis: a central nervous dysfunction of sweat secretion

Hyperhidrosis (HH) is a central nervous dysfunction characterized by abnormally increased sweating due to a central dysregulation of sweat secretion. HH significantly affects the quality of life of patients in their private, social and professional environments. Physiologically, sweating is a mechanism that regulates body temperature, but it may also be triggered by emotional or gustatory stimuli. There are two main types of sweat glands: eccrine and apocrine glands. The central nervous system controls sweat secretion through the release of neurotransmitters into the autonomous nervous system (ANS) that activate the sweat glands. The hypothalamus has two separate neuronal pathways, one for thermoregulation and one for emotions. HH may thus be due to either a neuronal dysfunction of ANS regulation leading to a hyperactivity of the sympathetic nervous system, or to abnormal central processing of emotions. Crucially, there is no dysfunction of the sweat glands themselves. Various pathogenic mechanisms have been proposed to be involved in pathological sweat secretion in HH, ranging from structural changes within the ANS to increased expression of aquaporin 5 and upregulation of activin A receptor type 1 in eccrine sweat glands. Although a genetic predisposition has been demonstrated, it remains unclear exactly which genes are involved. To identify new, potential therapeutic targets and to improve treatment options, a good understanding of the signaling pathways involved, the underlying mechanisms, and the genetic components is essential. In this review we discuss the various aspects of sweat physiology and function that are necessary to explain pathological sweating. Our aim is to raise awareness of the complexity of HH to promote a better understanding of the disorder

Sheaf theory for stacks in manifolds and twisted cohomology for S^1-gerbes

This is the first of a series of papers on sheaf theory on smooth and topological stacks and its applications. The main result of the present paper is the characterization of the twisted (by a closed integral three-form) de Rham complex on a manifold. As an object in the derived category it will be related with the push-forward of the constant sheaf from a S^1-gerbe with Dixmier-Douady class represented by the three-form. In order to formulate and prove this result we develop in detail the foundations of sheaf theory for smooth stacks.Comment: 39 pages, v2 typos corrected and references added. v3 confusion in 2.2.5 cleaned u

Na,K-ATPase on a waveguide sensor : supramolecular assembly and side directed binding studies by surface-confined fluorescence

Grell E, Pawlak M, Anselmetti D, Schick E, Lewitzki E, Ehrat M. Na,K-ATPase on a waveguide sensor : supramolecular assembly and side directed binding studies by surface-confined fluorescence. In: Taniguchi K, Kaya S, eds. Na/K-ATPase and related ATPases: proceedings of the 9th International Conference on the Na/K-ATPase and Related ATPases. Excerpta Medica international congress series. Vol 1207. Amsterdam: Elsevier; 2000: 437-440.The functional assembly of FITC-Na,K-ATPase membrane fragments on a surface-modified Ta2O5 waveguide allows to investigate the directed binding of ligands by surface-confined fluorescence studies. The results allow to draw conclusions about the sidedness of interactions. The fluorescence intensity decrease observed upon the selective binding of K+ is attributed to its coordination to a site accessible from the former intracellular membrane side