Iodine, thyroid autoimmunity and cancer

This review focuses on two different topics: (a) iodine and autoimmune thyroid disease (AITD) and (b) AITD and papillary thyroid carcinoma (PTC). Iodine intake modifies the expression of thyroid diseases and has been associated with induction of AITD. Thyroglobulin (Tg) is an important target in iodine-induced autoimmune response due to post-translational modifications of iodinated Tg, as suggested in animal models. We have shown that the unmasking of a cryptic epitope on Tg contributes to iodine-induced thyroid autoimmunity in humans. The relationship between AITD and PTC has been suggested in many studies. The presence of two different mechanisms has been hypothesized, one typical of AITD and the other of an immune reaction to PTC. We have shown that in AITD, the pattern of Tg recognition by anti-Tg antibodies (TgAb) is 'restricted' to the immunodominant regions of Tg, while in patients with non-AITD, such as nodular goiter and PTC devoid of thyroid lymphocytic infiltration at histology, TgAb show a less restricted epitopic pattern and bind also to other regions of Tg. Thyroid function may also affect the frequency of PTC, the risk of cancer increasing with serum TSH levels. We have shown that this mechanism, rather than thyroiditis per se, plays a major role in the association of PTC with Hashimoto's thyroiditis, as a consequence of the autoimmune process leading to a progressive increase of serum TSH in these patients

Multifidelity modeling for the design of re-entry capsules

The design and optimization of space systems presents many challenges associated with the variety of physical domains involved and their coupling. A practical example is the case of satellites and space vehicles designed to re-enter the atmosphere upon completion of their mission [1]. For these systems, aerodynamics and thermodynamics phenomena are strongly coupled and relate to structural dynamics and vibrations, chemical non equilibrium phenomena that characterize the atmosphere, specific re-entry trajectory, and geometrical shape of the body. Blunt bodies are common geometric configurations used in planetary re-entry (e.g. Apollo Command Module, Mars Viking probe, etc.). These geometries permit to obtain high aerodynamic resistance to decelerate the vehicle from orbital speeds along with contained aerodynamic lift for trajectory control. The large radius-of-curvature of the bodies’ nose allows to reduce the heat flux determined by the high temperature effects behind the shock wave. The design and optimization of these bodies would largely benefit from accurate analyses of the re-entry flow field through high-fidelity representations of the aerodynamic and aerothermodynamic phenomena. However, those high-fidelity representations are usually in the form of computer models for the numerical solutions of PDEs (e.g. Navier-Stokes equations, heat equations, etc.) which require significant computational effort and are commonly excluded from preliminary multidisciplinary design and trade-off analysis. This work addresses the integration of high-fidelity computer-based simulations for the multidisciplinary design of space systems conceived for controlled re-entry in the atmosphere. In particular, we discuss the use of multifidelity methods to obtain efficient aerothermodynamic models of the re-entering vehicles. Multifidelity approaches allow to accelerate the exploration and evaluation of design alternatives through the use of different representations of a physical system/process, each characterized by a different level of fidelity and associated computational expense [2, 3]. By efficiently combining less-expensive information from low-fidelity models with a principled selection of few expensive simulations, multifidelity methods allow to incorporate high-fidelity costly information for multidisciplinary design analysis and optimization [4–7]. This presentation proposes a multifidelity Bayesian optimization framework leveraging surrogate models in the form of gaussian processes, which are progressively updated through acquisition functions based on expected improvement. We introduce a novel formulation of the multifideltiy expected improvement including both data-driven and physics-informed utility functions, specifically implemented for the case of the design optimization of an Orion-like atmospheric re-entry vehicle. The results show that the proposed formulation gives better optimization results (lower minimum) than single fidelity Bayesian optimization based on low-fidelity simulations only. The outcome suggests that the multifidelity expected improvement algorithm effectively enriches the information content with the high-fidelity data. Moreover, the computational cost associated with 100 iterations of our multifidelity strategy is sensitively lower than the computational burden of 6 iterations of a single fidelity framework invoking the high-fidelity model. References [1] Gallais, P., Atmospheric re-entry vehicle mechanics, Springer Science and Business Media, 2007. [2] Peherstorfer, B., Willcox, K., and Gunzburger, M., “Survey of Multifidelity Methods in Uncertainty Propagation, Inference, and Optimization,” SIAM Review, Vol. 60, 2018, pp. 550–591. [3] Fernandez-Godino, G., Park, C., Kim, N., and Haftka, R., “Issues in Deciding Whether to Use Multifidelity Surrogates,” AIAA Journal, 2019, p. 16. [4] Mainini, L., and Maggiore, P., “A Multifidelity Approach to Aerodynamic Analysis in an Integrated Design Environment,” AIAA/ASME/ASCE/AHS/ASC Structures, Structural Dynamics and Materials Conference, AIAA, 2012. [5] Goertz, S., Zimmermann, R., and Han, Z. H., “Variable-fidelity and reduced-order models for aero data for loads predictions,” Computational Flight Testing, 2013, pp. 99–112. [6] Meliani, M., Bartoli, N., Lefebvre, T., Bouhlel, M.A., J., Martins, and Morlier, J., “Multi-fidelity efficient global optimization: Methodology and application to airfoil shape design,” AIAA Aviation 2019 Forum, AIAA, 2019. [7] Beran, P., Bryson, D., Thelen, A., Diez, M., and Serani, A., “Comparison of Multi-Fidelity Approaches for Military Vehicle Design,” AIAA Aviation 2020 Forum, AIAA, 2020

Multifidelity Learning for the Design of Re-Entry Capsules

The design and optimization of re-entry capsules presents many challenges associated with the variety of physical domains involved and their couplings. Examples are capsules for the transfer of astronauts to the international space station and for future Lunar and Martian exploration missions. For these vehicles, aerodynamics and thermodynamics phenomena are strongly coupled and relate to structural dynamics and vibrations, chemical non equilibrium phenomena that characterize the atmosphere, specifi c re-entry trajectory, and geometrical shape of the body. The design and optimization of these capsules would largely benefi t from accurate analyses of the re-entry flow field through high- fidelity representations of the aerothermodynamic phenomena. However, those high- fidelity representations are usually in the form of computer models for the numerical solutions of PDEs (e.g. Navier-Stokes equations, heat equations, etc.) which require signifi cant computational effort and are commonly excluded from preliminary multidisciplinary design and trade-off analysis. This presentation discusses the use of multi fidelity methods to integrate high- fidelity simulations in order to obtain efficient aerothermodynamic models of the re-entering vehicles. Multi fidelity approaches allow to accelerate the exploration and evaluation of design alternatives through the use of different representations of a physical system/process, each characterized by a different level of fidelity and associated computational expense. By efficiently combining less-expensive information from low- fidelity models with a principled selection of few expensive simulations, multi fidelity methods allow to incorporate high-fidelity costly information for design analysis and optimization. Speci fically, we propose a multifi delity active learning strategy to accelerate the multidisciplinary design optimization (MDO) of a re-entry vehicle. The active learning scheme is formulated to be both data driven and domain-aware, and is implemented for the design of an Orion-like re-entry capsule. The MDO problem comprises trajectory analysis, propulsion system model, aerothermodynamic models, and structural model of the thermal protection systems (TPS). The design objectives are the minimization of the propellant mass burned during the entry maneuver, the structural mass of the TPS and the temperature reached by the TPS structure. The results show that our multifidelity scheme allows to efficiently improve the design solution through a limited number of high- fidelity evaluations

Multifidelity domain-aware learning for the design of re-entry vehicles

The multidisciplinary design optimization (MDO) of re-entry vehicles presents many challenges associated with the plurality of the domains that characterize the design problem and the multi-physics interactions. Aerodynamic and thermodynamic phenomena are strongly coupled and relate to the heat loads that affect the vehicle along the re-entry trajectory, which drive the design of the thermal protection system (TPS). The preliminary design and optimization of re-entry vehicles would benefit from accurate high-fidelity aerothermodynamic analysis, which are usually expensive computational fluid dynamic simulations. We propose an original formulation for multifidelity active learning that considers both the information extracted from data and domain-specific knowledge. Our scheme is developed for the design of re-entry vehicles and is demonstrated for the case of an Orion-like capsule entering the Earth atmosphere. The design process aims to minimize the mass of propellant burned during the entry maneuver, the mass of the TPS, and the temperature experienced by the TPS along the re-entry. The results demonstrate that our multifidelity strategy allows to achieve a sensitive improvement of the design solution with respect to the baseline. In particular, the outcomes of our method are superior to the design obtained through a single-fidelity framework, as a result of the principled selection of a limited number of high-fidelity evaluations

The Metadistrict as the Territorial Strategy for Revitalizing the Rural Economy

The purpose of this proposal is to explore a new concept of 'Metadistrict' to be applied in a region of Southern Italy – Apulia - in order to analyze the impact that the activation of a special network between different sector chains and several integrated projects may have for revitalizing the local economy. The Metadistrict model stems from the LAGs and the IPFs frameworks and it may represent a crucial driver of the rural economy through the realization of sector circuits connected to the concept of multi-functionality in agriculture, that is Network of the Territorial Multi-functionality (NTM). It was formalized through a simplified model based on Matrix Organization. The adoption of the Metadistrict perspective as the territorial strategy may play a key role to revitalize the primary sector through the increase of economic and productive opportunities due to the implementation of a common and shared strategy and organization

The Metadistrict as the Territorial Strategy for Revitalizing the Rural Economy

The purpose of this proposal is to explore a new concept of 'Metadistrict' to be applied in a region of Southern Italy – Apulia - in order to analyze the impact that the activation of a special network between different sector chains and several integrated projects may have for revitalizing the local economy. The Metadistrict model stems from the LAGs and the IPFs frameworks and it may represent a crucial driver of the rural economy through the realization of sector circuits connected to the concept of multi-functionality in agriculture, that is Network of the Territorial Multi-functionality (NTM). It was formalized through a simplified model based on Matrix Organization. The adoption of the Metadistrict perspective as the territorial strategy may play a key role to revitalize the primary sector through the increase of economic and productive opportunities due to the implementation of a common and shared strategy and organization

Prestress and experimental tests on fractional viscoelastic materials

Creep and/or Relaxation tests on viscoelastic materials show a power-law trend. Based upon Boltzmann superposition principle the constitutive law with a power-law kernel is ruled by the Caputo's fractional derivative. Fractional constitutive law posses a long memory and then the parameters obtained by best fitting procedures on experimental data are strongly influenced by the prestress on the specimen. As in fact during the relaxation test the imposed history of deformation is not instantaneously applied, since a unit step function may not be realized by the test machine. Aim of this paper, it is shown that, the experimental procedure, and in particular the initial ramp to reach the constant stress (or strain) strongly influences the best fitting procedure and the coefficients of the power-law

MASW Terra-Mare, applicazione a Taranto per il Progetto Beleolico

Per una caratterizzazione sismica del sottosuolo presso la spiaggia dell’insediamento residenziale di "Lido Azzurro” (TA), area interessata alla realizzazione di un parco eolico “near-shore”, l'IAMC ha effettuato uno stendimento sismico del tipo terra-mare con metodologia MASW per la determinazione del profilo verticale delle onde di taglio e del valore Vs30, in riferimento tra l’altro alla classificazione dei terreni di fondazione degli interventi in progetto nelle categorie di suolo, come da paragrafo 3.2.2 delle N.T.C. 2008 “D.M. 14/01/2008”

Towards weighing the condensation energy to ascertain the Archimedes force of vacuum

The force exerted by the gravitational field on a Casimir cavity in terms of Archimedes force of vacuum is discussed, the force that can be tested against observation is identified, and it is shown that the present technology makes it possible to perform the first experimental tests. The use of suitable high-Tc superconductors as modulators of Archimedes force is motivated. The possibility is analyzed of using gravitational wave interferometers as detectors of the force, transported through an optical spring from the Archimedes vacuum force apparatus to the gravitational interferometer test masses to maintain the two systems well separated. The use of balances to actuate and detect the force is also analyzed, the different solutions are compared, and the most important experimental issues are discussed.Comment: Revtex, 33 pages, 8 figures. In the final version, the title has been changed, and all sections have been improved, while 2 appendices have been adde

The many faces of ubiquitinated histone H2A: insights from the DUBs

Monoubiquitination of H2A is a major histone modification in mammalian cells. Understanding how monoubiquitinated H2A (uH2A) regulates DNA-based processes in the context of chromatin is a challenging question. Work in the past years linked uH2A to transcriptional repression by the Polycomb group proteins of developmental regulators. Recently, a number of mammalian deubiquitinating enzymes (DUBs) that catalyze the removal of ubiquitin from H2A have been discovered. These studies provide convincing evidence that H2A deubiquitination is connected with gene activation. In addition, uH2A regulatory enzymes have crucial roles in the cellular response to DNA damage and in cell cycle progression. In this review we will discuss new insights into uH2A biology, with emphasis on the H2A DUBs