86 research outputs found

    Characterizing normal crossing hypersurfaces

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    The objective of this article is to give an effective algebraic characterization of normal crossing hypersurfaces in complex manifolds. It is shown that a hypersurface has normal crossings if and only if it is a free divisor, has a radical Jacobian ideal and a smooth normalization. Using K. Saito's theory of free divisors, also a characterization in terms of logarithmic differential forms and vector fields is found and and finally another one in terms of the logarithmic residue using recent results of M. Granger and M. Schulze.Comment: v2: typos fixed, final version to appear in Math. Ann.; 24 pages, 2 figure

    D-brane Categories for Orientifolds -- The Landau-Ginzburg Case

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    We construct and classify categories of D-branes in orientifolds based on Landau-Ginzburg models and their orbifolds. Consistency of the worldsheet parity action on the matrix factorizations plays the key role. This provides all the requisite data for an orientifold construction after embedding in string theory. One of our main results is a computation of topological field theory correlators on unoriented worldsheets, generalizing the formulas of Vafa and Kapustin-Li for oriented worldsheets, as well as the extension of these results to orbifolds. We also find a doubling of Knoerrer periodicity in the orientifold context.Comment: 45 pages, 6 figure

    Quiver GIT for varieties with tilting bundles

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    In the setting of a variety X admitting a tilting bundle T we consider the problem of constructing X as a quiver GIT quotient of the algebra A:=EndX(T)opA:=EndX(T)op . We prove that if the tilting equivalence restricts to a bijection between the skyscraper sheaves of X and the closed points of a quiver representation moduli functor for A=EndX(T)opA=EndX(T)op then X is indeed a fine moduli space for this moduli functor, and we prove this result without any assumptions on the singularities of X. As an application we consider varieties which are projective over an affine base such that the fibres are of dimension 1, and the derived pushforward of the structure sheaf on X is the structure sheaf on the base. In this situation there is a particular tilting bundle on X constructed by Van den Bergh, and our result allows us to reconstruct X as a quiver GIT quotient for an easy to describe stability condition and dimension vector. This result applies to flips and flops in the minimal model program, and in the situation of flops shows that both a variety and its flop appear as moduli spaces for algebras produced from different tilting bundles on the variety. We also give an application to rational surface singularities, showing that their minimal resolutions can always be constructed as quiver GIT quotients for specific dimension vectors and stability conditions. This gives a construction of minimal resolutions as moduli spaces for all rational surface singularities, generalising the G-Hilbert scheme moduli space construction which exists only for quotient singularities

    Landau-Ginzburg/Calabi-Yau correspondence, global mirror symmetry and Orlov equivalence

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    We show that the Gromov-Witten theory of Calabi-Yau hypersurfaces matches, in genus zero and after an analytic continuation, the quantum singularity theory (FJRW theory) recently introduced by Fan, Jarvis and Ruan following ideas of Witten. Moreover, on both sides, we highlight two remarkable integral local systems arising from the common formalism of Gamma-integral structures applied to the derived category of the hypersurface {W=0} and to the category of graded matrix factorizations of W. In this setup, we prove that the analytic continuation matches Orlov equivalence between the two above categories.Comment: 72pages, v2: Appendix B and references added. Typos corrected, v3: several mistakes corrected, final versio

    Comparison of TNFα to Lipopolysaccharide as an Inflammagen to Characterize the Idiosyncratic Hepatotoxicity Potential of Drugs: Trovafloxacin as an Example

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    Idiosyncratic drug reactions (IDRs) are poorly understood, unpredictable, and not detected in preclinical studies. Although the cause of these reactions is likely multi-factorial, one hypothesis is that an underlying inflammatory state lowers the tolerance to a xenobiotic. Previously used in an inflammation IDR model, bacterial lipopolysaccharide (LPS) is heterogeneous in nature, making development of standardized testing protocols difficult. Here, the use of rat tumor necrosis factor-α (TNFα) to replace LPS as an inflammatory stimulus was investigated. Sprague-Dawley rats were treated with separate preparations of LPS or TNFα, and hepatic transcriptomic effects were compared. TNFα showed enhanced consistency at the transcriptomic level compared to LPS. TNFα and LPS regulated similar biochemical pathways, although LPS was associated with more robust inflammatory signaling than TNFα. Rats were then codosed with TNFα and trovafloxacin (TVX), an IDR-associated drug, and evaluated by liver histopathology, clinical chemistry, and gene expression analysis. TNFα/TVX induced unique gene expression changes that clustered separately from TNFα/levofloxacin, a drug not associated with IDRs. TNFα/TVX cotreatment led to autoinduction of TNFα resulting in potentiation of underlying gene expression stress signals. Comparison of TNFα/TVX and LPS/TVX gene expression profiles revealed similarities in the regulation of biochemical pathways. In conclusion, TNFα could be used in lieu of LPS as an inflammatory stimulus in this model of IDRs

    Elevated 17β-Estradiol Protects Females from Influenza A Virus Pathogenesis by Suppressing Inflammatory Responses

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    Studies of the 1918 H1N1 influenza pandemic, the H5N1 avian influenza outbreak, and the 2009 H1N1 pandemic illustrate that sex and pregnancy contribute to severe outcome from infection, suggesting a role for sex steroids. To test the hypothesis that the sexes respond differently to influenza, the pathogenesis of influenza A virus infection was investigated in adult male and female C57BL/6 mice. Influenza infection reduced reproductive function in females and resulted in greater body mass loss, hypothermia, and mortality in females than males. Whereas lung virus titers were similar between the sexes, females had higher induction of proinflammatory cytokines and chemokines, including TNF-α, IFN-γ, IL-6, and CCL2, in their lungs than males. Removal of the gonads in both sexes eliminated the sex difference in influenza pathogenesis. Manipulation of testosterone or dihydrotestosterone concentrations in males did not significantly impact virus pathogenesis. Conversely, females administered high doses of estradiol had a ≥10-fold lower induction of TNF-α and CCL2 in the lungs and increased rates of survival as compared with females that had either low or no estradiol. The protective effects of estradiol on proinflammatory cytokines and chemokines, morbidity, and mortality were primarily mediated by signaling through estrogen receptor α (ERα). In summary, females suffer a worse outcome from influenza A virus infection than males, which can be reversed by administration of high doses of estradiol to females and reflects differences in the induction of proinflammatory responses and not in virus load

    Large Scale Comparison of Innate Responses to Viral and Bacterial Pathogens in Mouse and Macaque

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    Viral and bacterial infections of the lower respiratory tract are major causes of morbidity and mortality worldwide. Alveolar macrophages line the alveolar spaces and are the first cells of the immune system to respond to invading pathogens. To determine the similarities and differences between the responses of mice and macaques to invading pathogens we profiled alveolar macrophages from these species following infection with two viral (PR8 and Fuj/02 influenza A) and two bacterial (Mycobacterium tuberculosis and Francisella tularensis Schu S4) pathogens. Cells were collected at 6 time points following each infection and expression profiles were compared across and between species. Our analyses identified a core set of genes, activated in both species and across all pathogens that were predominantly part of the interferon response pathway. In addition, we identified similarities across species in the way innate immune cells respond to lethal versus non-lethal pathogens. On the other hand we also found several species and pathogen specific response patterns. These results provide new insights into mechanisms by which the innate immune system responds to, and interacts with, invading pathogens
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