579 research outputs found
Remarks on the naturality of quantization
Hamiltonian quantization of an integral compact symplectic manifold M depends
on a choice of compatible almost complex structure J. For open sets U in the
set of compatible almost complex structures and small enough values of Planck's
constant, the Hilbert spaces of the quantization form a bundle over U with a
natural connection. In this paper we examine the dependence of the Hilbert
spaces on the choice of J, by computing the semi-classical limit of the
curvature of this connection. We also show that parallel transport provides a
link between the action of the group Symp(M) of symplectomorphisms of M and the
Schrodinger equation.Comment: 20 page
A local families index formula for d-bar operators on punctured Riemann surfaces
Using heat kernel methods developed by Vaillant, a local index formula is
obtained for families of d-bar operators on the Teichmuller universal curve of
Riemann surfaces of genus g with n punctures. The formula also holds on the
moduli space M{g,n} in the sense of orbifolds where it can be written in terms
of Mumford-Morita-Miller classes. The degree two part of the formula gives the
curvature of the corresponding determinant line bundle equipped with the
Quillen connection, a result originally obtained by Takhtajan and Zograf.Comment: 47 page
Almost holomorphic embeddings in Grassmannians with applications to singular symplectic submanifolds
In this paper we use Donaldson's approximately holomorphic techniques to build embeddings of a closed symplectic manifold with symplectic form of integer class in the Grassmannians Gr(r, N). We assure that these embeddings are asymptotically holomorphic in a precise sense. We study first the particular case of CPN obtaining control on N and we improve in a sense a classical result about symplectic embeddings. The main reason of our Study is the construction of singular determinantal submanifolds as the intersection of the embedding with certain "generalized Schubert cycles" defined on a product of Grassmannians. It is shown that the symplectic type of these submanifolds is quite more general that the ones obtained by Donaldson and Auroux,as zeroes of "very ample" vector bundles
Klebsiella pneumoniae is able to trigger epithelial-mesenchymal transition process in cultured airway epithelial cells
The ability of some bacterial pathogens to activate Epithelial-Mesenchymal Transition normally is a consequence of the persistence of a local chronic inflammatory response or depends on a direct interaction of the pathogens with the host epithelial cells. In this study we monitored the abilities of the K. pneumoniae to activate the expression of genes related to EMT-like processes and the occurrence of phenotypic changes in airway epithelial cells during the early steps of cell infection. We describe changes in the production of intracellular reactive oxygen species and increased HIF-1α mRNA expression in cells exposed to K. pneumoniae infection. We also describe the upregulation of a set of transcription factors implicated in the EMT processes, such as Twist, Snail and ZEB, indicating that the morphological changes of epithelial cells already appreciable after few hours from the K. pneumoniae infection are tightly regulated by the activation of transcriptional pathways, driving epithelial cells to EMT. These effects appear to be effectively counteracted by resveratrol, an antioxidant that is able to exert a sustained scavenging of the intracellular ROS. This is the first report indicating that strains of K. pneumoniae may promote EMT-like programs through direct interaction with epithelial cells without the involvement of inflammatory cells
Mortality within 30 days of chemotherapy: a clinical governance benchmarking issue for oncology patients
No national benchmark figures exist for early mortality due to chemotherapy unlike for surgical interventions. Deaths within 30 days of chemotherapy during a 6-month period were identified from the Royal Marsden Hospital electronic patient records. Treatment intention – curative or palliative, cause of death and number of previous treatments – were documented. Between April 2005 and September 2005, 1976 patients received chemotherapy with 161 deaths within 30 days of chemotherapy (8.1%). Of these, 124 deaths (77.0%) were due to disease progression. Of the other 37 deaths, 12 (7.5%) were related to chemotherapy, six each for solid tumours and haematological malignancies, of which seven (4.3%) were due to neutropenic sepsis. For the remaining 25 deaths (15.5%) there was insufficient information. There were more deaths after third and subsequent lines of therapy than with first and secondlines of therapy. Only 12 of the 161 deaths occurred in patients who were receiving potentially curative chemotherapy to give a mortality rate in breast and gastrointestinal malignancy of 0.5 and 1.5%, respectively. It is possible to audit mortality within 30 days of chemotherapy and this should become a benchmark for standard practice nationally. Most deaths were due to disease progression in the palliative setting. We practice this form of audit each quarter and feed back to the treating teams so that deaths are discussed and practice monitored
Supercoherent States, Super K\"ahler Geometry and Geometric Quantization
Generalized coherent states provide a means of connecting square integrable
representations of a semi-simple Lie group with the symplectic geometry of some
of its homogeneous spaces. In the first part of the present work this point of
view is extended to the supersymmetric context, through the study of the
OSp(2/2) coherent states. These are explicitly constructed starting from the
known abstract typical and atypical representations of osp(2/2). Their
underlying geometries turn out to be those of supersymplectic OSp(2/2)
homogeneous spaces. Moment maps identifying the latter with coadjoint orbits of
OSp(2/2) are exhibited via Berezin's symbols. When considered within
Rothstein's general paradigm, these results lead to a natural general
definition of a super K\"ahler supermanifold, the supergeometry of which is
determined in terms of the usual geometry of holomorphic Hermitian vector
bundles over K\"ahler manifolds. In particular, the supergeometry of the above
orbits is interpreted in terms of the geometry of Einstein-Hermitian vector
bundles. In the second part, an extension of the full geometric quantization
procedure is applied to the same coadjoint orbits. Thanks to the super K\"ahler
character of the latter, this procedure leads to explicit super unitary
irreducible representations of OSp(2/2) in super Hilbert spaces of
superholomorphic sections of prequantum bundles of the Kostant type. This work
lays the foundations of a program aimed at classifying Lie supergroups'
coadjoint orbits and their associated irreducible representations, ultimately
leading to harmonic superanalysis. For this purpose a set of consistent
conventions is exhibited.Comment: 53 pages, AMS-LaTeX (or LaTeX+AMSfonts
Pellino-1 regulates the responses of the airway to viral infection
Exposure to respiratory pathogens is a leading cause of exacerbations of airway diseases such as asthma and chronic obstructive pulmonary disease (COPD). Pellino-1 is an E3 ubiquitin ligase known to regulate virally-induced inflammation. We wished to determine the role of Pellino-1 in the host response to respiratory viruses in health and disease. Pellino-1 expression was examined in bronchial sections from patients with GOLD stage two COPD and healthy controls. Primary bronchial epithelial cells (PBECs) in which Pellino-1 expression had been knocked down were extracellularly challenged with the TLR3 agonist poly(I:C). C57BL/6 Peli1−/− mice and wild type littermates were subjected to intranasal infection with clinically-relevant respiratory viruses: rhinovirus (RV1B) and influenza A. We found that Pellino-1 is expressed in the airways of normal subjects and those with COPD, and that Pellino-1 regulates TLR3 signaling and responses to airways viruses. In particular we observed that knockout of Pellino-1 in the murine lung resulted in increased production of proinflammatory cytokines IL-6 and TNFα upon viral infection, accompanied by enhanced recruitment of immune cells to the airways, without any change in viral replication. Pellino-1 therefore regulates inflammatory airway responses without altering replication of respiratory viruses
Marriage, Duty and Civilization: Keshab Chandra Sen and the Cuch Bihar Controversy in Metropolitan and Colonial Context
A Mammalian Target of Rapamycin-Perilipin 3 (mTORC1-Plin3) Pathway is essential to Activate Lipophagy and Protects Against Hepatosteatosis
[Background and Aims] NAFLD is the most common hepatic pathology in western countries and no treatment is currently available. NAFLD is characterized by the aberrant hepatocellular accumulation of fatty acids in the form of lipid droplets (LDs). Recently, it was shown that liver LD degradation occurs through a process termed lipophagy, a form of autophagy. However, the molecular mechanisms governing liver lipophagy are elusive. Here, we aimed to ascertain the key molecular players that regulate hepatic lipophagy and their importance in NAFLD.[Approach and Results] We analyzed the formation and degradation of LD in vitro (fibroblasts and primary mouse hepatocytes), in vivo and ex vivo (mouse and human liver slices) and focused on the role of the autophagy master regulator mammalian target of rapamycin complex (mTORC) 1 and the LD coating protein perilipin (Plin) 3 in these processes. We show that the autophagy machinery is recruited to the LD on hepatic overload of oleic acid in all experimental settings. This led to activation of lipophagy, a process that was abolished by Plin3 knockdown using RNA interference. Furthermore, Plin3 directly interacted with the autophagy proteins focal adhesion interaction protein 200 KDa and autophagy-related 16L, suggesting that Plin3 functions as a docking protein or is involved in autophagosome formation to activate lipophagy. Finally, we show that mTORC1 phosphorylated Plin3 to promote LD degradation.[Conclusions] These results reveal that mTORC1 regulates liver lipophagy through a mechanism dependent on Plin3 phosphorylation. We propose that stimulating this pathway can enhance lipophagy in hepatocytes to help protect the liver from lipid-mediated toxicity, thus offering a therapeutic strategy in NAFLD.Supported by C0120R3166, C0245R4032, and BH182173 from Newcastle University. M. G.-M. is a Sara Borrell Postdoctoral fellow (CD18/00203) from the Ministerio de Ciencia, Innovación y Universidades (Spain). J. P. B. is funded by the Agencia Estatal de Investigación, grants PID2019-105699RB-I00/AEI/10.13039/501100011033 and RED2018-102576-T, Instituto de Salud Carlos III (CB16/10/00282), Junta de Castilla y León (Escalera de Excelencia CLU-2017-03), Ayudas Equipos Investigación Biomedicina 2017 Fundación BBVA, and Fundación Ramón Areces. V. I. K. acknowledges support from Biotechnology and Biological Sciences Research Council (BB/M023389/1, BB/R008167/1, BBPeer reviewe
Ingraft chimerism in lung transplantation - a study in a porcine model of obliterative bronchiolitis
<p>Abstract</p> <p>Background</p> <p>Bronchial epithelium is a target of the alloimmune response in lung transplantation, and intact epithelium may protect allografts from rejection and obliterative bronchiolitis (OB). Herein we study the influence of chimerism on bronchial epithelium and OB development in pigs.</p> <p>Methods</p> <p>A total of 54 immunosuppressed and unimmunosuppressed bronchial allografts were serially obtained 2-90 days after transplantation. Histology (H&E) was assessed and the fluorescence in situ hybridization (FISH) method for Y chromosomes using pig-specific DNA-label was used to detect recipient derived cells in graft epithelium and bronchial wall, and donor cell migration to recipient organs. Ingraft chimerism was studied by using male recipients with female donors, whereas donor cell migration to recipient organs was studied using female recipients with male donors.</p> <p>Results</p> <p>Early appearance of recipient-derived cells in the airway epithelium appeared predictive of epithelial destruction (<it>R </it>= 0.610 - 0.671 and <it>p </it>< 0.05) and of obliteration of the bronchial lumen (<it>R </it>= 0.698 and <it>p </it>< 0.01). All allografts with preserved epithelium showed epithelial chimerism throughout the follow-up. Antirejection medication did not prevent, but delayed the appearance of Y chromosome positive cells in the epithelium (<it>p </it>< 0.05), or bronchial wall (<it>p </it>< 0.05).</p> <p>Conclusions</p> <p>In this study we demonstrate that early appearance of Y chromosomes in the airway epithelium predicts features characteristic of OB. Chimerism occurred in all allografts, including those without features of OB. Therefore we suggest that ingraft chimerism may be a mechanism involved in the repair of alloimmune-mediated tissue injury after transplantation.</p
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