Time filter

Source Type

Trinti B.,CNR Institute of Biomedical Engineering
Annali dell'Istituto Superiore di Sanita | Year: 2010

In celiac disease (CD), for its multifactorial nature, the target organs are not limited to the gut, but include thyroid, liver, skin and reproductive and nervous systems. Between the extraintestinal symptoms associated with CD, autoimmune thyroid diseases (AITDs) are more evident, underlining as CD-related autoimmune alterations can be modulated not only by gluten but also by various concurrent endogenous (genetic affinity, over-expression of cytokines) and exogenous (environment, nutritional deficiency) factors. In their pathogenesis a central role for over-expression of interleukin-15 (IL-15) is shown, by inhibiting apoptosis, leading to the perpetuation of inflammation and tissue destruction. Thyroid is particularly sensitive to selenium deficiency because selenoproteins are significant in biosynthesis and activity of thyroid hormones; besides, some selenoproteins as glutathione peroxidase are involved in inhibiting apoptosis. Thus, selenium malabsorption in CD can be thought as a key factor directly leading to thyroid and intestinal damage. Considering the complexity of this interaction and on the basis of available evidence, the aim of this review is to assess as preventive and therapeutic target the role of IL-15 and selenium in the pathogeneses of both CD and AITD.

Giorgino T.,CNR Institute of Biomedical Engineering
Computer Physics Communications | Year: 2014

Molecular dynamics simulations have a prominent role in biophysics and drug discovery due to the atomistic information they provide on the structure, energetics and dynamics of biomolecules. Specialized software packages are required to analyze simulated trajectories, either interactively or via scripts, to derive quantities of interest and provide insight for further experiments. This paper presents the Density Profile Tool, a package that enhances the Visual Molecular Dynamics environment with the ability to interactively compute and visualize 1-D projections of various density functions of molecular models. We describe how the plugin is used to perform computations both via a graphical interface and programmatically. Results are presented for realistic examples, all-atom bilayer models, showing how mass and electron densities readily provide measurements such as membrane thickness, location of structural elements, and how they compare to X-ray diffraction experiments. © 2013 Elsevier B.V. All rights reserved.

Giorgino T.,CNR Institute of Biomedical Engineering
Computer Physics Communications | Year: 2014

PLUMED-GUI is an interactive environment to develop and test complex PLUMED scripts within the Visual Molecular Dynamics (VMD) environment. Computational biophysicists can take advantage of both PLUMED's rich syntax to define collective variables (CVs) and VMD's chemically-aware atom selection language, while working within a natural point-and-click interface. Pre-defined templates and syntax mnemonics facilitate the definition of well-known reaction coordinates. Complex CVs, e.g. involving reference snapshots used for RMSD or native contacts calculations, can be built through dialogs that provide a synoptic view of the available options. Scripts can be either exported for use in simulation programs, or evaluated on the currently loaded molecular trajectories. Script development takes place without leaving VMD, thus enabling an incremental try-see-modify development model for molecular metrics. © 2014 Published by Elsevier B.V.

Michaliszyn S.F.,University of Pittsburgh | Mari A.,CNR Institute of Biomedical Engineering | Lee S.,University of Pittsburgh | Bacha F.,Baylor College of Medicine | And 4 more authors.
Diabetes | Year: 2014

Using the hyperglycemic and euglycemic clamp, we demonstrated impaired β-cell function in obese youth with increasing dysglycemia. Herein we describe oral glucose tolerance test (OGTT)-modeled β-cell function and incretin effect in obese adolescents spanning the range of glucose tolerance. β-Cell function parameters were derived from established mathematical models yielding β-cell glucose sensitivity (bCGS), rate sensitivity, and insulin sensitivity in 255 obese adolescents (173 with normal glucose tolerance [NGT], 48 with impaired glucose tolerance [IGT], and 34 with type 2 diabetes [T2D]). The incretin effect was calculated as the ratio of the OGTT-bCGS to the 2-h hyperglycemic clamp-bCGS. Incretin and glucagon concentrations were measured during the OGTT. Compared with NGT, βCGS was 30 and 65% lower in youth with IGT and T2D, respectively; rate sensitivity was 40% lower in T2D. Youth with IGT or T2D had 32 and 38% reduced incretin effect compared with NGT in the face of similar changes in GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) in response to oral glucose. We conclude that glucose sensitivity deteriorates progressively in obese youth across the spectrum of glucose tolerance in association with impairment in incretin effect without reduction in GLP-1 or GIP, similar to that seen in adult dysglycemia. © 2014 by the American Diabetes Association.

Finesso L.,CNR Institute of Biomedical Engineering | Grassi A.,CNR Institute of Biomedical Engineering | Spreij P.,University of Amsterdam
Mathematics of Control, Signals, and Systems | Year: 2010

Stochastic realization is still an open problem for the class of hidden Markov models (HMM): given the law Q of an HMM find a finite parametric description of it. Fifty years after the introduction of HMMs, no computationally effective realization algorithm has been proposed. In this paper we direct our attention to an approximate version of the stochastic realization problem for HMMs. We aim at the realization of an HMM of assigned complexity (number of states of the underlying Markov chain) which best approximates, in Kullback Leibler divergence rate, a given stationary law Q. In the special case of Q being the law of an HMM this corresponds to solving the approximate realization problem for HMMs. In general there is no closed form expression of the Kullback Leibler divergence rate, therefore we replace it, as approximation criterion, with the informational divergence between the Hankel matrices of the processes. This not only has the advantage of being easy to compute, while providing a good approximation of the divergence rate, but also makes the problem amenable to the use of nonnegative matrix factorization (NMF) techniques. We propose a three step algorithm, based on the NMF, which realizes an optimal HMM. The viability of the algorithm as a practical tool is tested on a few examples of HMM order reduction. © 2010 The Author(s).

Discover hidden collaborations