44 research outputs found

    Homotopical resolutions associated to deformable adjunctions

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    Given an adjunction connecting reasonable categories with weak equivalences, we define a new derived bar and cobar construction associated to the adjunction. This yields homotopical models of the completion and cocompletion associated to the monad and comonad of the adjunction. We discuss applications of these resolutions to spectral sequences for derived completions and Goodwillie calculus in general model categories.Comment: 22 pages; v2 is the final journal version, with expository improvements suggested by the refere

    A universal characterization of higher algebraic K-theory

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    In this paper we establish a universal characterization of higher algebraic K-theory in the setting of small stable infinity categories. Specifically, we prove that connective algebraic K-theory is the universal additive invariant, i.e., the universal functor with values in spectra which inverts Morita equivalences, preserves filtered colimits, and satisfies Waldhausen's additivity theorem. Similarly, we prove that non-connective algebraic K-theory is the universal localizing invariant, i.e., the universal functor that moreover satisfies the "Thomason-Trobaugh-Neeman" localization theorem. To prove these results, we construct and study two stable infinity categories of "noncommutative motives"; one associated to additivity and another to localization. In these stable infinity categories, Waldhausen's S. construction corresponds to the suspension functor and connective and non-connective algebraic K-theory spectra become corepresentable by the noncommutative motive of the sphere spectrum. In particular, the algebraic K-theory of every scheme, stack, and ring spectrum can be recovered from these categories of noncommutative motives. In order to work with these categories of noncommutative motives, we establish comparison theorems between the category of spectral categories localized at the Morita equivalences and the category of small idempotent-complete stable infinity categories. We also explain in detail the comparison between the infinity categorical version of Waldhausen K-theory and the classical definition. As an application of our theory, we obtain a complete classification of the natural transformations from higher algebraic K-theory to topological Hochschild homology (THH) and topological cyclic homology (TC). Notably, we obtain an elegant conceptual description of the cyclotomic trace map.Comment: Various revisions and correction

    Type 2 diabetes mellitus and cerebrospinal fluid Alzheimer's disease biomarker amyloid β1-42 in Alzheimer's Disease Neuroimaging Initiative participants

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    Introduction Type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer's disease. Cerebrospinal fluid (CSF) amyloid β (Aβ) 1-42 is an important Alzheimer's disease biomarker. However, it is inconclusive on how T2DM is related to CSF Aβ1-42. Methods Participants with T2DM were selected from the Alzheimer's Disease Neuroimaging Initiative by searching keywords from the medical history database. A two-way analysis of covariance model was used to analyze how T2DM associates with CSF Aβ1-42 or cerebral cortical Aβ. Results CSF Aβ1-42 was higher in the T2DM group than the nondiabetic group. The inverse relation between CSF Aβ1-42 and cerebral cortical Aβ was independent of T2DM status. Participants with T2DM had a lower cerebral cortical Aβ in anterior cingulate, precuneus, and temporal lobe than controls. Discussion T2DM is positively associated with CSF Aβ1-42 but negatively with cerebral cortical Aβ. The decreased cerebral cortical Aβ associated with T2DM is preferentially located in certain brain regions

    Topological Hochschild homology of Thom spectra and the free loop space

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    We describe the topological Hochschild homology of ring spectra that arise as Thom spectra for loop maps f: X->BF, where BF denotes the classifying space for stable spherical fibrations. To do this, we consider symmetric monoidal models of the category of spaces over BF and corresponding strong symmetric monoidal Thom spectrum functors. Our main result identifies the topological Hochschild homology as the Thom spectrum of a certain stable bundle over the free loop space L(BX). This leads to explicit calculations of the topological Hochschild homology for a large class of ring spectra, including all of the classical cobordism spectra MO, MSO, MU, etc., and the Eilenberg-Mac Lane spectra HZ/p and HZ.Comment: 58 page

    Galois theory and Lubin-Tate cochains on classifying spaces

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    We consider brave new cochain extensions F(BG +,R) → F(EG +,R), where R is either a Lubin-Tate spectrum E n or the related 2-periodic Morava K-theory K n , and G is a finite group. When R is an Eilenberg-Mac Lane spectrum, in some good cases such an extension is a G-Galois extension in the sense of John Rognes, but not always faithful. We prove that for E n and K n these extensions are always faithful in the K n local category. However, for a cyclic p-group C p r, the cochain extension F(BC p r +,E n ) → F(EC p r +, E n ) is not a Galois extension because it ramifies. As a consequence, it follows that the E n -theory Eilenberg-Moore spectral sequence for G and BG does not always converge to its expected target

    Topological Andr\'e-Quillen homology for cellular commutative SS-algebras

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    Topological Andr\'e-Quillen homology for commutative SS-algebras was introduced by Basterra following work of Kriz, and has been intensively studied by several authors. In this paper we discuss it as a homology theory on CW SS-algebras and apply it to obtain results on minimal atomic pp-local SS-algebras which generalise those of Baker and May for pp-local spectra and simply connected spaces. We exhibit some new examples of minimal atomic SS-algebras.Comment: Final revision, a version will appear in Abhandlungen aus dem Mathematischen Seminar der Universitaet Hambur

    Lrp4 Mediates Bone Homeostasis and Mechanotransduction through Interaction with Sclerostin In Vivo

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    Wnt signaling plays a key role in regulating bone remodeling. In vitro studies suggest that sclerostin's inhibitory action on Lrp5 is facilitated by the membrane-associated receptor Lrp4. We generated an Lrp4 R1170W knockin mouse model (Lrp4KI), based on a published mutation in patients with high bone mass (HBM). Lrp4KI mice have an HBM phenotype (assessed radiographically), including increased bone strength and formation. Overexpression of a Sost transgene had osteopenic effects in Lrp4-WT but not Lrp4KI mice. Conversely, sclerostin inhibition had blunted osteoanabolic effects in Lrp4KI mice. In a disuse-induced bone wasting model, Lrp4KI mice exhibit significantly less bone loss than wild-type (WT) mice. In summary, mice harboring the Lrp4-R1170W missense mutation recapitulate the human HBM phenotype, are less sensitive to altered sclerostin levels, and are protected from disuse-induced bone loss. Lrp4 is an attractive target for pharmacological targeting aimed at increasing bone mass and preventing bone loss due to disuse

    Protein phosphatase 2A plays a crucial role in Giardia lamblia differentiation

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    Author Posting. © The Authors, 2006. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Molecular and Biochemical Parasitology 152 (2007): 80-89, doi:10.1016/j.molbiopara.2006.12.001.The ability of Giardia lamblia to undergo two distinct differentiations in response to physiologic stimuli is central to its pathogenesis. The giardial cytoskeleton changes drastically during encystation and excystation. However, the signal transduction pathways mediating these transformations are poorly understood. We tested the hypothesis that PP2A, a highly conserved serine/threonine protein phosphatase, might be important in giardial differentiation. We found that in vegetatively growing trophozoites, gPP2A-C protein localizes to basal bodies/centrosomes, and to cytoskeletal structures unique to Giardia: the ventral disk, and the dense rods of the anterior, posterior-lateral, and caudal flagella. During encystation, gPP2A-C protein disappears from only the anterior flagellar dense rods. During excystation, gPP2A-C localizes to the cyst wall in excysting cysts but is not found in the wall of cysts with emerging excyzoites. Transcriptome and immunoblot analyses indicated that gPP2A-C mRNA and protein are upregulated in mature cysts and during the early stage of excystation that models passage through the host stomach. Stable expression of gPP2A-C antisense RNA did not affect vegetative growth, but strongly inhibited the formation of encystation secretory vesicles (ESV) and water-resistant cysts. Moreover, the few cysts that formed were highly defective in excystation. Thus, gPP2A-C localizes to universal cytoskeletal structures and to structures unique to Giardia. It is also important for encystation and excystation, crucial giardial transformations that entail entry into and exit from dormancy.This work was funded by NIH grants GM61896, AI51687, AI42488, and DK35108. Dr. A.G. McArthur was supported by NIH grant AI51089 and the Marine Biological Laboratory’s Program in Global Infectious Diseases, funded by the Ellison Medical Foundation
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