498 research outputs found
On the Structure of the Small Quantum Cohomology Rings of Projective Hypersurfaces
We give an explicit procedure which computes for degree the
correlation functions of topological sigma model (A-model) on a projective Fano
hypersurface as homogeneous polynomials of degree in the correlation
functions of degree 1 (number of lines). We extend this formalism to the case
of Calabi-Yau hypersurfaces and explain how the polynomial property is
preserved. Our key tool is the construction of universal recursive formulas
which express the structural constants of the quantum cohomology ring of as
weighted homogeneous polynomial functions in the constants of the Fano
hypersurface with the same degree and dimension one more. We propose some
conjectures about the existence and the form of the recursive formulas for the
structural constants of rational curves of arbitrary degree. Our recursive
formulas should yield the coefficients of the hypergeometric series used in the
mirror calculation. Assuming the validity of the conjectures we find the
recursive laws for rational curves of degree 4 and 5.Comment: 32 pages, changed fonts, exact results on quintic rational curves are
added. To appear in Commun. Math. Phy
The Fano normal function
The Fano surface of lines in the cubic threefold is naturally embedded in the intermediate Jacobian , we call 'Fano cycle' the difference , this is homologous to 0 in . We study the normal function on the moduli space which computes the Abel-Jacobi image of the Fano cycle. By means of the related infinitesimal invariant we can prove that the primitive part of the normal function is not of torsion. As a consequence we get that, for a general is not algebraically equivalent to zero in (proved also by van der Geer and Kouvidakis (2010) [15] with different methods) and, moreover, that there is no divisor in containing both and and such that these surfaces are homologically equivalent in the divisor. Our study of the infinitesimal variation of Hodge structure for produces intrinsically a threefold in the Grassmannian of lines in . We show that the infinitesimal invariant at attached to the normal function gives a section of a natural bundle on and more specifically that this section vanishes exactly on , which turns out to be the curve in parameterizing the 'double lines' in the threefold. We prove that this curve reconstructs and hence we get a Torelli-like result: the infinitesimal invariant for the Fano cycle determines
CHARACTERIZATION OF GENETIC AND EPIGENETIC MODIFICATIONS IN A MODEL OF INFLAMMATION-DRIVEN CANCER
Chronic inflammation is causally associated to many types of tumor, and has been recently acknowledged as a cancer hallmark. Nevertheless, whether inflammation has an intrinsic mutagenic potential is still not directly proven or understood from a mechanistic point of view. Furthermore, it is as yet unclear whether inflammation could induce epigenetic modifications, and if these changes are relevant to tumor generation.
Therefore, the aim of this work was to assess inflammation-derived genomic and epigenomic modifications at multiple stages of tumorigenesis in Mdr2-knockout mice, a model of purely inflammatory hepatocellular carcinoma (HCC).
By ChIPseq profiling of H3K27Ac mark we reported the establishment of an inflammatory program specifically in hepatocytes starting from the pre-malignant, chronic inflammatory step. This inflammatory signature is retained up to the more advanced HCC stage, and is accompanied by the activation of members of the AP1 transcription factor family.
In parallel, by whole exome sequencing, we observed a high frequency of copy number amplifications and a very low number of point mutations in HCC nodules. Copy number variations occurrence was directly correlated to the grade of malignancy in each lesion. The JNK pathway was shown to be pervasively targeted by gene amplification, and to be involved in the adenoma-to-carcinoma transition. A comparable genetic landscape has been observed in a human liver cancer with similar etiology.
In conclusion, this study shows that in a model of inflammation-driven cancer an epigenetic inflammatory signature is early acquired and maintained throughout disease progression. On the contrary, genetic alterations appear only at later stages and mainly target the JNK pathway. Future dataset integration will help clarifying chronological relationship and possible mutual interplay between mutations and epigenetic changes
PPARs as new therapeutic targets for the treatment of cerebral ischemia/reperfusion injury.
Stroke is a leading cause of death and long-term disability in industrialized countries. Despite advances in understanding its pathophysiology, little progress has been made in the treatment of stroke. The currently available therapies have proven to be highly unsatisfactory (except thrombolysis) and attempts are being made to identify and characterize signaling proteins which could be exploited to design novel therapeutic modalities. The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that control lipid and glucose metabolism. PPARs regulate gene expression by binding with the retinoid X receptor (RXR) as a heterodimeric partner to specific DNA sequences, termed PPAR response elements. In addition, PPARs may modulate gene transcription also by directly interfering with other transcription factor pathways in a DNA-binding independent manner. To date, three different PPAR isoforms, designated α, β/ δ, and γ, have been identified. Recently, they have been found to play an important role for the pathogenesis of various disorders of the central nervous system and accumulating data suggest that PPARs may serve as potential targets for treating ischemic stroke. Activation of all PPAR isoforms, but especially of PPAR γ, was shown to prevent post-ischemic inflammation and neuronal damage in several in vitro and in vivo models, negatively regulating the expression of genes induced by ischemia/ reperfusion (I/R). This paper reviews the evidence and recent developments relating to the potential therapeutic effects of PPAR-agonists in the treatment of cerebral I/R injury
Flipping the molecular switch for innate protection and repair of tissues: Long-lasting effects of a non-erythropoietic small peptide engineered from erythropoietin.
The NLRP3 Inflammasome as a Novel Player of the Intercellular Crosstalk in Metabolic Disorders
The combination of obesity and type 2 diabetes is a serious health problem, which is projected to afflict 300 million people worldwide by 2020. Both clinical and translational laboratory studies have demonstrated that chronic inflammation is associated with obesity and obesity-related conditions such as insulin resistance. However, the precise etiopathogenetic mechanisms linking obesity to diabetes remain to be elucidated, and the pathways that mediate this phenomenon are not fully characterized. One of the most recently identified signaling pathways, whose activation seems to affect many metabolic disorders, is the “inflammasome,” a multiprotein complex composed of NLRP3 (nucleotide-binding domain and leucine-rich repeat protein 3), ASC (apoptosis-associated speck-like protein containing a CARD), and procaspase-1. NLRP3 inflammasome activation leads to the processing and secretion of the proinflammatory cytokines interleukin- (IL-) 1β and IL-18. The goal of this paper is to review new insights on the effects of the NLRP3 inflammasome activation in the complex mechanisms of crosstalk between different organs, for a better understanding of the role of chronic inflammation in metabolic disease pathogenesis. We will provide here a perspective on the current research on NLRP3 inflammasome, which may represent an innovative therapeutic target to reverse the detrimental metabolic consequences of the metabolic inflammation
Remarks on hard Lefschetz conjectures on Chow groups
We propose two conjectures of Hard Lefschetz type on Chow groups and prove
them for some special cases. For abelian varieties, we shall show they are
equivalent to well-known conjectures of Beauville and Murre.Comment: to appear in Sciences in China, Ser. A Mathematic
Enhanced sphingosine-1-phosphate levels by pharmacological or genetic approaches attenuate cardiac dysfunction in experimental septic cardiomyopathy
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