Localization algebras and deformations of Koszul algebras

We show that the center of a flat graded deformation of a standard Koszul algebra behaves in many ways like the torus-equivariant cohomology ring of an algebraic variety with finite fixed-point set. In particular, the center acts by characters on the deformed standard modules, providing a "localization map." We construct a universal graded deformation, and show that the spectrum of its center is supported on a certain arrangement of hyperplanes which is orthogonal to the arrangement coming the Koszul dual algebra. This is an algebraic version of a duality discovered by Goresky and MacPherson between the equivariant cohomology rings of partial flag varieties and Springer fibers; we recover and generalize their result by showing that the center of the universal deformation for the ring governing a block of parabolic category $\mathcal{O}$ for $\mathfrak{gl}_n$ is isomorphic to the equivariant cohomology of a Spaltenstein variety. We also identify the center of the deformed version of the "category $\mathcal{O}$" of a hyperplane arrangement (defined by the authors in a previous paper) with the equivariant cohomology of a hypertoric variety.Comment: 39 pages; v3: final versio

Diversity of Xenorhabdus and Photorhabdus spp. and their symbiotic entomopathogenic nematodes from Thailand

Xenorhabdus and Photorhabdus spp. are bacterial symbionts of entomopathogenic nematodes (EPNs). In this study, we isolated and characterized Xenorhabdus and Photorhabdus spp. from across Thailand together with their associated nematode symbionts, and characterized their phylogenetic diversity. EPNs were isolated from soil samples using a Galleria-baiting technique. Bacteria from EPNs were cultured and genotyped based on recA sequence. The nematodes were identified based on sequences of 28S rDNA and internal transcribed spacer regions. A total of 795 soil samples were collected from 159 sites in 13 provinces across Thailand. A total of 126 EPNs isolated from samples taken from 10 provinces were positive for Xenorhabdus (n = 69) or Photorhabdus spp. (n = 57). Phylogenetic analysis separated the 69 Xenorhabdus isolates into 4 groups. Groups 1, 2 and 3 consisting of 52, 13 and 1 isolates related to X. stockiae, and group 4 consisting of 3 isolates related to X. miraniensis. The EPN host for isolates related to X. stockiae was S. websteri, and for X. miraniensis was S. khoisanae. The Photorhabdus species were identified as P. luminescens (n = 56) and P. asymbiotica (n = 1). Phylogenenic analysis divided P. luminescens into five groups. Groups 1 and 2 consisted of 45 and 8 isolates defined as subspecies hainanensis and akhurstii, respectively. One isolate was related to hainanensis and akhurstii, two isolates were related to laumondii, and one isolate was the pathogenic species P. asymbiotica subsp. australis. H. indica was the major EPN host for Photorhabdus. This study reveals the genetic diversity of Xenorhabdus and Photorhabdus spp. and describes new associations between EPNs and their bacterial symbionts in Thailand

Caffeine consumption disrupts hippocampal long-term potentiation in freely behaving rats.

Caffeine, one of the most commonly consumed psychoactive substances in the world, has long been known to alter neurological functions, such as alertness, attention, and memory. Despite caffeine\u27s popularity, systematic investigations of its effects on synaptic plasticity in the brain are still lacking. Here we used a freely behaving rodent model of long-term potentiation (LTP), a frequently studied form of synaptic plasticity, to assess the effects of caffeine consumption on hippocampal plasticity. LTP, which is a persistent increase in the strength of synaptic connections between neurons, is a cellular mechanism widely considered to underlie the processes of learning and memory. A group of 10-week-old Sprague-Dawley rats were administered caffeine (1 g/L) in their drinking water 3 weeks prior to collection of electrophysiological data. Another group of age-matched animals received tap water and served as controls. Stimulating and recording electrodes were chronically implanted in the perforant pathway (PP) and dentate gyrus (DG) region of the hippocampus, respectively, to permit stable electrophysiological recordings of synaptic transmission at this synapse. Population spike amplitude (PSA) measures of LTP induction and duration were acquired in vivo while animals were freely behaving using a well-established electrophysiological recording protocol. Results indicate caffeine-treated rats (n = 9) had a significantly (P \u3c 0.05) reduced level of LTP induction compared with controls (n = 10). More studies are needed to identify the exact mechanism through which caffeine alters LTP induction in this freely behaving model of synaptic plasticity

TNF and IL‐6 mediate MIP‐1α expression in bleomycin‐induced lung injury

Previously, macrophage inflammatory protein‐1α (MIP‐1α), a member of the C‐C chemokine family, has been implicated in bleomycin‐induced pulmonary fibrosis, a model of the human disease idiopathic pulmonary fibrosis. Neutralization of MIP‐1α protein with anti‐MIP‐1α antibodies significantly attenuated both mononuclear phagocyte recruitment and pulmonary fibrosis in bleomycin‐challenged CBA/J mice. However, the specific stimuli for MIP‐1α expression in the bleomycin‐induced lesion have not been characterized. In this report, two mediators of the inflammatory response to bleomycin, tumor necrosis factor (TNF) and interleukin‐6 (IL‐6), were evaluated as putative stimuli for MIP‐1α expression after bleomycin challenge in CBA/J mice. Elevated levels of bioactive TNF and IL‐6 were detected in bronchoalveolar lavage (BAL) fluid and lung homogenates from bleomycin‐treated CBA/J mice at time points post‐bleomycin challenge, which precede MIP‐1α protein expression. Treatment of bleomycin‐challenged mice with soluble TNF receptor (sTNFr) or anti‐IL‐6 antibodies significantly decreased MIP‐1α protein expression in the lungs. Furthermore, normal alveolar macrophages secreted elevated levels of MIP‐1α protein in response to treatment with TNF plus IL‐6 or bleomycin plus IL‐6, but not TNF, bleomycin, or IL‐6 alone. Finally, leukocytes recovered from the BAL fluid of bleomycin‐challenged mice secreted higher levels of MIP‐1α protein, compared to controls, when treated with TNF alone. Based on the data presented here, we propose that TNF and IL‐6 are part of a cytokine network that modulates MIP‐1α protein expression in the profibrotic inflammatory lesion during the response to intratracheal bleomycin challenge. J. Leukoc. Biol. 64: 528–536; 1998.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141711/1/jlb0528.pd

The role of ILâ 5 in bleomycinâ induced pulmonary fibrosis

Eosinophils are known to express cytokines capable of promoting fibrosis. Interleukinâ 5 (ILâ 5) is important in regulating eosinophilopoiesis, eosinophil recruitment and activation. Lung ILâ 5 expression is elevated in pulmonary fibrosis, wherein the eosinophil is a primary source of fibrogenic cytokines. To determine the role of ILâ 5 in pulmonary fibrosis, the effects of antiâ ILâ 5 antibody were investigated in a model of bleomycinâ induced pulmonary fibrosis. Fibrosis was induced in mice by endotracheal bleomycin treatment. Animals were also treated with either antiâ ILâ 5 antibody or control IgG. Lungs were then analyzed for fibrosis, eosinophil influx, chemotactic activity, and cytokine expression. The results show that a primary chemotactic activity at the height of eosinophil recruitment is ILâ 5. Furthermore, antiâ ILâ 5 antibody caused significant reduction in lung eosinophilia, cytokine expression, and fibrosis. These findings taken together suggest an important role for ILâ 5 in pulmonary fibrosis via its ability to regulate eosinophilic inflammation, and thus eosinophilâ dependent fibrogenic cytokine production. J. Leukoc. Biol. 64: 657â 666; 1998.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141191/1/jlb0657.pd

Fatigue crack growth behavior under multiaxial variable amplitude loading

This study compares both uniaxial and multiaxial variable amplitude experimental crack growth data for naturally initiated fatigue cracks in tubular specimens of 2024-T3 aluminum alloy to predictions based on two state-of-the-art analysis codes: UniGrow and FASTRAN. For variable amplitude fatigue tests performed under pure axial nominal loading conditions, both UniGrow and FASTRAN analyses were found to produce mostly conservative growth life predictions, despite good agreement with constant amplitude crack growth data. For variable amplitude torsion and combined axial-torsion crack growth analyses, however, the conservatism in growth life predictions was found to reduce. This was attributed to multiaxial nominal stress state effects, such as T-stress and mixed-mode crack growth, which are not accounted for in either UniGrow or FASTRAN, but were found in constant amplitude fatigue tests to increase experimental crack growth rates. Since cracks in this study were initiated naturally, different initial crack geometry assumptions were also investigated in the analyse

A role for C‐C chemokines in fibrotic lung disease

Pulmonary fibrosis is the end point of a chronic inflammatory process characterized by leukocyte recruitment and activation, fibroblast proliferation, and increased extracellular matrix production. Previous studies of models of pulmonary fibrosis have investigated the role of cytokines in the evolution of the fibrotic response. The involvement of tumor necrosis factor and interleukin‐1 in bleomycin‐induced lung injury, a model of idiopathic pulmonary fibrosis, has been well established, suggesting that cytokines mediate the initiation and maintenance of chronic inflammatory lesions. However, the aforementioned cytokines alone cannot account for the recruitment and activation of specific leukocyte populations found in the bleomycin model. Recently, a family of novel proinflammatory cytokines (chemokines) was cloned and characterized, yielding many putative mediators of leukocyte functions. Macrophage inflammatory protein‐1α (MIP‐1α) and monocyte chemoattractant protein‐1 (MCP‐1) belong to the C‐C chemotactic cytokine family, a group of low‐molecular‐weight peptides. These molecules modulate chemotaxis, proliferation, and cytokine expression in leukocyte subsets. Our group has investigated the roles of MCP‐1 and MIP‐1α in the bleomycin model. Both MCP‐1 and MIP‐1α are expressed in a time‐dependent manner after bleomycin challenge, and passive immunization of these animals with either anti‐MIP‐1α or anti‐MCP‐1 antibodies attenuated leukocyte accumulation. In addition, we have identified specific cell types expressing MCP‐1 or MIP‐1α by in situ hybridization and immunohistochemical localization, respectively. Furthermore, our results indicate that MIP‐1α expression is mediated by alveolar macrophage‐derived tumor necrosis factor, identifying an important cytokine pathway in the initiation of pulmonary fibrosis. Finally, anti‐MIP‐1α therapy attenuated fibrosis, providing direct evidence for its involvement in fibrotic pathology. Our work has clearly established that the C‐C chemokines MCP‐1 and MIP‐1α are expressed and contribute to the initiation and maintenance of the bleomycin‐induced pulmonary lesion. J. Leukoc. Biol. 57: 782–787; 1995.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141648/1/jlb0782.pd

Essential role of stem cell factor–c‐Kit signalling pathway in bleomycin‐induced pulmonary fibrosis

Stem cell factor ( SCF ) and its receptor c‐Kit have been implicated in tissue remodelling and fibrosis. Alveolar fibroblasts from patients with diffuse interstitial fibrosis secrete more SCF . However, its precise role remains unclear. In this study the potential role of the SCF –c‐Kit axis in pulmonary fibrosis was examined. Fibrosis was induced by intratracheal instillation of bleomycin ( BLM ), which caused increased SCF levels in plasma, bronchoalveolar lavage fluid ( BALF ) and lung tissue, as well as increased expression by lung fibroblasts. These changes were accompanied by increased numbers of bone marrow‐derived c‐Kit + cells in the lung, with corresponding depletion in bone marrow. Both recombinant SCF and lung extracts from BLM ‐treated animals induced bone‐marrow cell migration, which was blocked by c‐Kit inhibitor. The migrated cells promoted myofibroblast differentiation when co‐cultured with fibroblasts, suggesting a paracrine pathogenic role. Interestingly, lung fibroblast cultures contained a subpopulation of cells that expressed functionally active c‐Kit, which were significantly greater and more responsive to SCF induction when isolated from fibrotic lungs, including those from patients with idiopathic pulmonary fibrosis ( IPF ). This c‐Kit + subpopulation was α SMA ‐negative and expressed lower levels of collagen I but significantly higher levels of TGF β than c‐Kit‐negative cells. SCF deficiency achieved by intratracheal treatment with neutralizing anti‐ SCF antibody or by use of Kitl Sl / Kitl Sl ‐d mutant mice in vivo resulted in significant reduction in pulmonary fibrosis. Taken together, the SCF –c‐Kit pathway was activated in BLM ‐injured lung and might play a direct role in pulmonary fibrosis by the recruitment of bone marrow progenitor cells capable of promoting lung myofibroblast differentiation. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98368/1/path4177.pd

Impact of structural disorder on the magnetic ordering and magnetocaloric response of amorphous Gd-based microwires.

We have studied the impact of structural disorder on the magnetic ordering and magnetocaloric response of amorphous Gd 68 Ni 32 and Gd 53 Al 24 Co 20 Zr 3 microwires. We find that the presence of structural disorder significantly broadens the paramagnetic to ferromagnetic (PM-FM) transition and the temperature-dependent magnetic entropy change, while the nature of the second-order magnetic transition and long-range ferromagnetic order are not essentially affected by this effect. The large magnetic moment of Gd and the presence of the long-range ferromagnetic order are believed to result in a large magnetic entropy change, which together with the broadening of the PM-FM transition due to structural disorder contribute to a large refrigerant capacity. The excellent magnetocaloric properties of the amorphous microwires make them very promising candidates for active magnetic refrigeration