The role of unfolded protein deposits in cardiac dysfunction

In this study we investigated the role of unfolded proteins as a toxic insult for cardiomyocytes in idiopathic dilated cardiomyopathy (DCM). We first confirmed the presence of amyloid fibers in DCM cardiomyocytes by histological and ultrastructural analysis, showing their preferentially intracellular distribution. These molecular species seem to coexist with low-complexity β-folded precursors (oligomers) which in our experiments could promote increase of systolic Ca2+ in normal cardiomyocytes and alterations of contractility. Our results suggest that these molecular species trigger the overexpression of UPR components such as GRPs, Chop and Caspase 12. In addition we demonstrated the presence of interactions between presenilins (PS) and Serca2a, suggesting a regulatory role of these Alzheimer’s-related proteins on the Ca2+ pump. The genetic analysis of the presenilin genes in DCM samples identified two undescribed mutations in the promoter of PS1, which appeared to inhibit the expression of the protein. The quantification of the presenilin levels showed a considerable decrease of PS2 associated with an increase of PS1. In order to characterize the protein(s) involved in the aggregasomes, we developed a series of purification protocols, which, unfortunately, did not identify a single protein species. As an alternative approach, we focused on the identification of transcripts differentially expressed in iDCM. Our study introduces an innovative three-group analysis in which we used amyloid samples to eliminate the interference related to the accumulation of unfolded peptides and deriving from the progression of HF. Interestingly we recognized a limited number of iDCM-specific genes, including nestin and DSCR1, which are normally correlated to neural development. In conclusion, our findings open intriguing perspectives to increase our knowledge of the etiology and progression of DCM. However further investigation is required to identify the protein(s) involved in the formation of the aggregasomes and the role of these molecular structures in the etiology of the disease

Fission induced by nucleons at intermediate energies

Monte Carlo calculations of fission of actinides and pre-actinides induced by protons and neutrons in the energy range from 100 MeV to 1 GeV are carried out by means of a recent version of the Li\`ege Intranuclear Cascade Model, INCL++, coupled with two different evaporation-fission codes, GEMINI++ and ABLA07. In order to reproduce experimental fission cross sections, model parameters are usually adjusted on available (p,f) cross sections and used to predict (n,f) cross sections for the same isotopes.Comment: 36 pages, 18 figures, to appear in Nuclear Physics

Gamma-convergence of quadratic functionals perturbed by bounded linear functionals

Given a bounded open set $\Omega\subset \mathbb{R}^n$, we study sequences of quadratic functionals on the Sobolev space $H^1_0(\Omega)$, perturbed by sequences of bounded linear functionals. We prove that their $\Gamma$-limits, in the weak topology of $H^1_0(\Omega)$, can always be written as the sum of a quadratic functional, a linear functional, and a non-positive constant. The classical theory of $G$- and $H$-convergence completely characterises the quadratic and linear parts of the $\Gamma$-limit and shows that their coefficients do not depend on $\Omega$. The constant, which instead depends on $\Omega$ and will be denoted by $-\nu(\Omega)$, plays an important role in the study of the limit behaviour of the energies of the solutions. The main result of this paper is that, passing to a subsequence, we can prove that $\nu$ coincides with a non-negative Radon measure on a sufficiently large collection of bounded open sets $\Omega$. Moreover, we exhibit an example that shows that the previous result cannot be obtained for every bounded open set. The specific form of this example shows that the compactness theorem for the localisation method in $\Gamma$-convergence cannot be easily improved

A design pattern for multimodal and multidevice user interfaces

In this paper, we introduce the MVIC pattern for creating multidevice and multimodal interfaces. We discuss the advantages provided by introducing a new component to the MVC pattern for those interfaces which must adapt to different devices and modalities. The proposed solution is based on an input model defining equivalent and complementary sequence of inputs for the same interaction. In addition, we discuss Djestit, a javascript library which allows creating multidevice and multimodal input models for web applications, applying the aforementioned pattern. The library supports the integration of multiple devices (Kinect 2, Leap Motion, touchscreens) and different modalities (gestural, vocal and touch). Copyright is held by the owner/author(s)

Transmission conditions obtained by homogenisation

Given a bounded open set in Rn, n 652, and a sequence (Kj) of compact sets converging to an (n-1)-dimensional manifold M, we study the asymptotic behaviour of the solutions to some minimum problems for integral functionals on \u3a9\Kj, with Neumann boundary conditions on 02(\u3a9\Kj). We prove that the limit of these solutions is a minimiser of the same functional on \u3a9\M subjected to a transmission condition on M, which can be expressed through a measure \ub5 supported on M. The class of all measures that can be obtained in this way is characterised, and the link between the measure \ub5 and the sequence (Kj) is expressed by means of suitable local minimum problems

Object-oriented modelling of a flexible beam including geometric nonlinearities

In this paper, an efficient approach for the modelling and simulation of slender beams subject to heavy inertial loads is presented. The limitations imposed by a linear formulation of elasticity are overcome by a second order expansion of the displacement field, based on a geometrical exact beam model. In light of this, the nonlinearities of the elastic terms are shifted as inertial contributions, which yields an expression of the equations of motion in closed form. Thanks to the formulation in closed form, the proposed model is implemented in Modelica, with particular care to the suitability of the model with respect to the Modelica Multibody library. After describing the model formulation and implementation, the paper presents some simulation results, in order to validate the model with respect to benchmarks, widely adopted in literature

Wind Characteristics in the Wake of a Non-Rotating Wind Turbine close to a Hill

Hilly terrain may considerably influence energy yield and structural loading of wind turbines. Wind energy developers are therefore required to accurately predict wind characteristics at the wind farm site already in the designing phase. It is necessary to determine how particular hill shape and size affect wind characteristics at the location of wind turbines operating in the wake of a hill. In order to address this complex issue, small-scale laboratory experiments were carried out in a boundary layer wind tunnel (BLWT). The focus was on characteristics of the flow at the same position downstream of the hill and the wind turbine models studied on various sizes and shapes of the hill model. Three hill models (a small and a large hill with laterally uniform heights and a hill with a bay) were exposed to the thermally neutrally stratified atmospheric boundary layer (ABL) simulation. In each experiment, there was only one hill model in the BLWT test section. The configuration without the hill, i.e. the flat terrain model, was tested as a reference case. Downstream of the hill model, there was a single (alone-standing) wind turbine model. Flow characteristics were studied downstream (behind) the wind turbine model. The wind turbine model was in the parking position in order to study wind characteristics in the situation with a strong wind when there is no rotation of rotor blades. The experimental results indicate a velocity decrease and stronger turbulence in the wind turbine wake in the presence of a hill, which trend is more pronounced in the case of larger hills. Strong velocity gradients are observed around the hub height in the large hill configuration, while this velocity deficit is the smallest in the hill with a bay configuration due to flow channeling. The velocity power spectra reveal the characteristic peak due to the vortex shedding from the hill ridge. The obtained results provide a new insight into the turbulent wake characteristics of a single wind turbine placed downstream of a hill with a potential to serve as a validation tool for computational studies

Exploring the magnetic properties and magnetic coupling in SrFe12O19/Co1-xZnxFe2O4 nanocomposites

Abstract Among hard/soft nanocomposites (NCs), ferrite-based materials are potentially promising for developing exchange-coupled systems, thus leading to enhanced magnetic properties. In this regard, we investigate the role of the synthesis approach in the development of SrFe12O19/CoFe2O4 (SFO/CFO) NCs, with special focus on tuning the magnetic features of the softer phase (CFO) by introducing Zn2+ in the spinel structure. X-ray powder diffraction (XRPD), transmission electron microscopy (TEM) and squid magnetometry were employed to clarify the relationship between morphology, size, and magnetic properties of the NCs, pointing out the feasibility of this method in obtaining successfully exchange-coupled systems. This work shows how optimizing the intrinsic magnetic properties of the CFO may be used to tune the extrinsic ones of the NCs. Despite the promising results in magnetic coupling, our study clearly confirms/strengthens that an enhancement of remanent magnetization is the most important factor for improving the magnetic performance