GFINDer: Genome Function INtegrated Discoverer through dynamic annotation, statistical analysis, and mining

Statisticalandclustering analyses ofgeneexpression results from high-density microarray experiments produce lists of hundreds of genes regulated differentially, or with particular expression profiles, in the conditions under study. Independent of the microarray platforms and analysis methods used, these lists must be biologically interpreted to gain a better knowledge of the patho-physiological phenomena involved. To this end, numerous biological annotations are available within heterogeneous and widely distributed databases. Although several tools have been developed for annotating lists of genes, most of them do not give methods for evaluating the relevance of the annotations provided, or for estimating the functional bias introduced by the gene set on the array used to identify the gene list considered. We developed Genome Functional INtegrated Discoverer (GFINDer ), a web server able to automatically provide large-scale lists of user-classified genes with functional profiles biologically characterizing the different gene classes in the list. GFINDer automatically retrieves annotations of several functional categories from different sources, identifies the categories enriched in each class of a user-classified gene list and calculates statistical significance values for each category. Moreover, GFINDer enables the functional classification of genes according to mined functional categories and the statistical analysis is of the classifications obtained, aiding better interpretationof microarray experiment results. GFINDer is available online at http://www.medinfopoli.polimi.it/GFINDer/

From ten to four and back again: how to generalize the geometry

We discuss the four-dimensional N=1 effective approach in the study of warped type II flux compactifications with SU(3)x SU(3)-structure to AdS_4 or flat Minkowski space-time. The non-trivial warping makes it natural to use a supergravity formulation invariant under local complexified Weyl transformations. We obtain the classical superpotential from a standard argument involving domain walls and generalized calibrations and show how the resulting F-flatness and D-flatness equations exactly reproduce the full ten-dimensional supersymmetry equations. Furthermore, we consider the effect of non-perturbative corrections to this superpotential arising from gaugino condensation or Euclidean D-brane instantons. For the latter we derive the supersymmetry conditions in N=1 flux vacua in full generality. We find that the non-perturbative corrections induce a quantum deformation of the internal generalized geometry. Smeared instantons allow to understand KKLT-like AdS vacua from a ten-dimensional point of view. On the other hand, non-smeared instantons in IIB warped Calabi-Yau compactifications 'destabilize' the Calabi-Yau complex structure into a genuine generalized complex one. This deformation gives a geometrical explanation of the non-trivial superpotential for mobile D3-branes induced by the non-perturbative corrections.Comment: LaTeX, 47 pages, v2, references, hyperref added, v3, correcting small inaccuracies in eqs. (2.6a) and (5.16

The extreme function theory for damage detection: An application to civil and aerospace structures

Any damaged condition is a rare occurrence for mechanical systems, as it is very unlikely to be observed. Thus, it represents an extreme deviation from the median of its probability distribu-tion. It is, therefore, necessary to apply proper statistical solutions, i.e., Rare Event Modelling (REM). The classic tool for this aim is the Extreme Value Theory (EVT), which deals with uni-or multivariate scalar values. The Extreme Function Theory (EFT), on the other hand, is defined by enlarging the fundamental EVT concepts to whole functions. When combined with Gaussian Process Regres-sion (GPR), the EFT is perfectly suited for mode shape-based outlier detection. In fact, it is possible to investigate the structure’s normal modes as a whole rather than focusing on their constituent data points, with quantifiable advantages. This provides a useful tool for Structural Health Monitoring, especially to reduce false alarms. This recently proposed methodology is here tested and validated both numerically and experimentally for different examples coming from Civil and Aerospace Engineering applications. One-dimensional beamlike elements with several boundary conditions are considered, as well as a two-dimensional plate-like spar and a frame structure

Deformations of calibrated D-branes in flux generalized complex manifolds

We study massless deformations of generalized calibrated cycles, which describe, in the language of generalized complex geometry, supersymmetric D-branes in N=1 supersymmetric compactifications with fluxes. We find that the deformations are classified by the first cohomology group of a Lie algebroid canonically associated to the generalized calibrated cycle, seen as a generalized complex submanifold with respect to the integrable generalized complex structure of the bulk. We provide examples in the SU(3) structure case and in a `genuine' generalized complex structure case. We discuss cases of lifting of massless modes due to world-volume fluxes, background fluxes and a generalized complex structure that changes type.Comment: 52 pages, added references, added comment on ellipticity in appendix B, made minor changes according to instructions referee JHE

Pheochromocytoma and Paraganglioma: Current Functional and Future Molecular Imaging

Paragangliomas are neural crest-derived tumors, arising either from chromaffin sympathetic tissue (in adrenal, abdominal, intra-pelvic, or thoracic paraganglia) or from parasympathetic tissue (in head and neck paraganglia). They have a specific cellular metabolism, with the ability to synthesize, store, and secrete catecholamines (although most head and neck paragangliomas do not secrete any catecholamines). This disease is rare and also very heterogeneous, with various presentations (e.g., in regards to localization, multifocality, potential to metastasize, biochemical phenotype, and genetic background). With growing knowledge, notably about the pathophysiology and genetic background, guidelines are evolving rapidly. In this context, functional imaging is a challenge for the management of paragangliomas. Nuclear imaging has been used for exploring paragangliomas for the last three decades, with MIBG historically as the first-line exam. Tracers used in paragangliomas can be grouped in three different categories. Agents that specifically target catecholamine synthesis, storage, and secretion pathways include: 123 and 131I-metaiodobenzylguanidine (123/131I-MIBG), 18F-fluorodopamine (18F-FDA), and 18F-fluorodihydroxyphenylalanine (18F-FDOPA). Agents that bind somatostatin receptors include 111In-pentetreotide and 68Ga-labeled somatostatin analog peptides (68Ga-DOTA-TOC, 68Ga-DOTA-NOC, 68Ga-DOTA-TATE). The non-specific agent most commonly used in paragangliomas is 18F-fluorodeoxyglucose (18F-FDG). This review will first describe conventional scintigraphic exams that are used for imaging paragangliomas. In the second part we will emphasize the interest in new PET approaches (specific and non-specific), considering the growing knowledge about genetic background and pathophysiology, with the aim of understanding how tumors behave, and optimally adjusting imaging technique for each tumor type

The general (2,2) gauged sigma model with three--form flux

We find the conditions under which a Riemannian manifold equipped with a closed three-form and a vector field define an on--shell N=(2,2) supersymmetric gauged sigma model. The conditions are that the manifold admits a twisted generalized Kaehler structure, that the vector field preserves this structure, and that a so--called generalized moment map exists for it. By a theorem in generalized complex geometry, these conditions imply that the quotient is again a twisted generalized Kaehler manifold; this is in perfect agreement with expectations from the renormalization group flow. This method can produce new N=(2,2) models with NS flux, extending the usual Kaehler quotient construction based on Kaehler gauged sigma models.Comment: 24 pages. v2: typos fixed, other minor correction

The Dual Role of the Pervasive "Fattish" Tissue Remodeling With Age

Human aging is characterized by dramatic changes in body mass composition that include a general increase of the total fat mass. Within the fat mass, a change in the proportions of adipose tissues also occurs with aging, affecting body metabolism, and playing a central role in many chronic diseases, including insulin resistance, obesity, cardiovascular diseases, and type II diabetes. In mammals, fat accumulates as white (WAT) and brown (BAT) adipose tissue, which differ both in morphology and function. While WAT is involved in lipid storage and immuno-endocrine responses, BAT is aimed at generating heat. With advancing age BAT declines, while WAT increases reaching the maximum peak by early old age and changes its distribution toward a higher proportion of visceral WAT. However, lipids tend to accumulate also within lipid droplets (LDs) in non-adipose tissues, including muscle, liver, and heart. The excess of such ectopic lipid deposition and the alteration of LD homeostasis contribute to the pathogenesis of the above-mentioned age-related diseases. It is not clear why age-associated tissue remodeling seems to lean toward lipid deposition as a "default program." However, it can be noted that such remodeling is not inevitably detrimental. In fact, such a programmed redistribution of fat throughout life could be considered physiological and even protective, in particular at extreme old age. In this regard, it has to be considered that an excessive decrease of subcutaneous peripheral fat is associated with a pro-inflammatory status, and a decrease of LD is associated with lipotoxicity leading to an increased risk of insulin resistance, type II diabetes and cardiovascular diseases. At variance, a balanced rate of fat content and distribution has beneficial effects for health and metabolic homeostasis, positively affecting longevity. In this review, we will summarize the present knowledge on the mechanisms of the age-related changes in lipid distribution and we will discuss how fat mass negatively or positively impacts on human health and longevity

Reformulating Supersymmetry with a Generalized Dolbeault Operator

The conditions for N=1 supersymmetry in type II supergravity have been previously reformulated in terms of generalized complex geometry. We improve that reformulation so as to completely eliminate the remaining explicit dependence on the metric. Doing so involves a natural generalization of the Dolbeault operator. As an application, we present some general arguments about supersymmetric moduli. In particular, a subset of them are then classified by a certain cohomology. We also argue that the Dolbeault reformulation should make it easier to find existence theorems for the N=1 equations.Comment: 30 pages, no figures. v2: minor correction

Supersymmetric D-branes and calibrations on general N=1 backgrounds

We study the conditions to have supersymmetric D-branes on general {\cal N}=1 backgrounds with Ramond-Ramond fluxes. These conditions can be written in terms of the two pure spinors associated to the SU(3)\times SU(3) structure on T_M\oplus T^\star_M, and can be split into two parts each involving a different pure spinor. The first involves the integrable pure spinor and requires the D-brane to wrap a generalised complex submanifold with respect to the generalised complex structure associated to it. The second contains the non-integrable pure spinor and is related to the stability of the brane. The two conditions can be rephrased as a generalised calibration condition for the brane. The results preserve the generalised mirror symmetry relating the type IIA and IIB backgrounds considered, giving further evidence for this duality.Comment: 23 pages. Some improvements and clarifications, typos corrected and references added. v3: Version published in JHE

D-branes on AdS flux compactifications

We study D-branes in N=1 flux compactifications to AdS_4. We derive their supersymmetry conditions and express them in terms of background generalized calibrations. Basically because AdS has a boundary, the analysis of stability is more subtle and qualitatively different from the usual case of Minkowski compactifications. For instance, stable D-branes filling AdS_4 may wrap trivial internal cycles. Our analysis gives a geometric realization of the four-dimensional field theory approach of Freedman and collaborators. Furthermore, the one-to-one correspondence between the supersymmetry conditions of the background and the existence of generalized calibrations for D-branes is clarified and extended to any supersymmetric flux background that admits a time-like Killing vector and for which all fields are time-independent with respect to the associated time. As explicit examples, we discuss supersymmetric D-branes on IIA nearly Kaehler AdS_4 flux compactifications.Comment: 43 pages, 2 pictures, 1 table; v2: added references, color to figure and corrected typo in (6.21b