Existence, Uniqueness and Convergence of Simultaneous Distributed-Boundary Optimal Control Problems

We consider a steady-state heat conduction problem $P$ for the Poisson equation with mixed boundary conditions in a bounded multidimensional domain $\Omega$. We also consider a family of problems $P_{\alpha}$ for the same Poisson equation with mixed boundary conditions being $\alpha>0$ the heat transfer coefficient defined on a portion $\Gamma_{1}$ of the boundary. We formulate simultaneous \emph{distributed and Neumann boundary} optimal control problems on the internal energy $g$ within $\Omega$ and the heat flux $q$, defined on the complementary portion $\Gamma_{2}$ of the boundary of $\Omega$ for quadratic cost functional. Here the control variable is the vector $(g,q)$. We prove existence and uniqueness of the optimal control $(\overline{\overline{g}},\overline{\overline{q}})$ for the system state of $P$, and $(\overline{\overline{g}}_{\alpha},\overline{\overline{q}}_{\alpha})$ for the system state of $P_{\alpha}$, for each $\alpha>0$, and we give the corresponding optimality conditions. We prove strong convergence, in suitable Sobolev spaces, of the vectorial optimal controls, system and adjoint states governed by the problems $P_{\alpha}$ to the corresponding vectorial optimal control, system and adjoint states governed by the problem $P$, when the parameter $\alpha$ goes to infinity. We also obtain estimations between the solutions of these vectorial optimal control problems and the solution of two scalar optimal control problems characterized by fixed $g$ (with boundary optimal control $\overline{q}$) and fixed $q$ (with distributed optimal control $\overline{g}$), respectively, for both cases $\alpha>0$ and $\alpha=\infty$.Comment: 14 page

Effect of Ceramic Scaffold Architectural Parameters on Biological Response.

Numerous studies have focused on the optimization of ceramic architectures to fulfill a variety of scaffold functional requirements and improve biological response. Conventional fabrication techniques, however, do not allow for the production of geometrically controlled, reproducible structures and often fail to allow the independent variation of individual geometric parameters. Current developments in additive manufacturing technologies suggest that 3D printing will allow a more controlled and systematic exploration of scaffold architectures. This more direct translation of design into structure requires a pipeline for design-driven optimization. A theoretical framework for systematic design and evaluation of architectural parameters on biological response is presented. Four levels of architecture are considered, namely (1) surface topography, (2) pore size and geometry, (3) porous networks, and (4) macroscopic pore arrangement, including the potential for spatially varied architectures. Studies exploring the effect of various parameters within these levels are reviewed. This framework will hopefully allow uncovering of new relationships between architecture and biological response in a more systematic way as well as inform future refinement of fabrication techniques to fulfill architectural necessities with a consideration of biological implications.The authors gratefully acknowledge the financial support of the Gates Cambridge Trust and Geistlich Pharma AG.This is the final version of the article. It first appeared from Frontiers via http://dx.doi.org/10.3389/fbioe.2015.0015

Co-targeting the IGF system and HIF-1 inhibits migration and invasion by (triple-negative) breast cancer cells

BACKGROUND: Metastatic triple-negative breast cancer is mostly incurable, due to lack of suitable drug targets. The insulin-like growth factor (IGF) system could provide such a target, and IGF-1 receptor (IGF-1R)-directed agents are already available, but seem unable to control all the complexities of the system, including crosstalk with hypoxia-inducible pathways. METHODS: Migration of triple-negative MDA-231 breast cancer cells and its modulation by IGFs, the IGF-1R inhibitor NVP-AEW541 and the IGF-2-sequestering monoclonal antibody MAB292 were assessed by the scratch wound healing and Boyden chamber assays; the effect of topotecan (inhibiting hypoxia-inducible factor-1 (HIF-1)) under hypoxia was also evaluated. Constitutive as well as drug-modulated levels of components of the IGF and HIF-1 pathways were evaluated by western blotting and qPCR. RESULTS: IGF-induced migration of MDA-231 cells was not abrogated by the IGF-1R inhibitor NVP-AEW541, whereas IGF-2 sequestration by MAB292 significantly reduced cell migration. Under hypoxia, topotecan was also effective, likely by reducing HIF-1-induced IGF-2 release. Simultaneous targeting of IGF-1R and IGF-2 or HIF-1 completely abolished cell migration. CONCLUSIONS: IR activation may account for the failure of NVP-AEW541 to suppress MDA-231 cell migration. Ligand-targeting compounds, or co-inhibition of the IGF and HIF-1 systems, may prevent activation of compensatory signalling, thereby providing a valuable addition to IGF-1R inhibitor-based therapies

Proteomic analysis of dopamine and \u3b1-synuclein interplay in a cellular model of Parkinson's disease pathogenesis

Altered dopamine homeostasis is an accepted mechanism in the pathogenesis of Parkinson\u2019s disease. a-Synuclein overexpression and impaired disposal contribute to this mechanism. However, biochemical alterations associated with the interplay of cytosolic dopamine and increased a-synuclein are still unclear. Catecholaminergic SH-SY5Y human neuroblastoma cells are a suitable model for investigating dopamine toxicity. In the present study, we report the proteomic pattern of SH-SY5Y cells overexpressing a-synuclein (1.6-fold induction) after dopamine exposure. Dopamine itself is able to upregulate a-synuclein expression. However, the effect is not observed in cells that already overexpress a-synuclein as a consequence of transfection. The proteomic analysis highlights significant changes in 23 proteins linked to specific cellular processes, such as cytoskeleton structure and regulation, mitochondrial function, energetic metabolism, protein synthesis, and neuronal plasticity. A bioinformatic network enrichment procedure generates a significant model encompassing all proteins and allows us to enrich functional categories associated with the combination of factors analyzed in the present study (i.e. dopamine together with a-synuclein). In particular, the model suggests a potential involvement of the nuclear factor kappa B pathway that is experimentally confirmed. Indeed, a-synuclein significantly reduces nuclear factor kappa B activation, which is completely quenched by dopamine treatment.Altered dopamine homeostasis is an accepted mechanism in the pathogenesis of Parkinson's disease. \u3b1-Synuclein overexpression and impaired disposal contribute to this mechanism. However, biochemical alterations associated with the interplay of cytosolic dopamine and increased \u3b1-synuclein are still unclear. Catecholaminergic SH-SY5Y human neuroblastoma cells are a suitable model for investigating dopamine toxicity. In the present study, we report the proteomic pattern of SH-SY5Y cells overexpressing \u3b1-synuclein (1.6-fold induction) after dopamine exposure. Dopamine itself is able to upregulate \u3b1-synuclein expression. However, the effect is not observed in cells that already overexpress \u3b1-synuclein as a consequence of transfection. The proteomic analysis highlights significant changes in 23 proteins linked to specific cellular processes, such as cytoskeleton structure and regulation, mitochondrial function, energetic metabolism, protein synthesis, and neuronal plasticity. A bioinformatic network enrichment procedure generates a significant model encompassing all proteins and allows us to enrich functional categories associated with the combination of factors analyzed in the present study (i.e. dopamine together with \u3b1-synuclein). In particular, the model suggests a potential involvement of the nuclear factor kappa B pathway that is experimentally confirmed. Indeed, \u3b1-synuclein significantly reduces nuclear factor kappa B activation, which is completely quenched by dopamine treatment. \ua9 2010 The Authors Journal compilation \ua9 2010 FEBS

Valutazione del rischio elettromagnetico ai sensi del D.Lgs. 81/2008 presso l\u27Azienda Ospedaliera Mellino Mellini Chiari (Brescia)

.La relazione riferisce i risultati della campagna di misura effettuata nei giorni dal 6 al 9 giugno 2011 e successivamente il 4 e il 6 luglio 2011. La campagna ? stata preceduta da un sopralluogo (21 marzo 2011) alle strutture di competenza dell\u27Azienda Mellino Mellini (Chiari, Iseo, Rovato, Palazzolo ed Orzinuovi) per la definizione delle azioni da intraprendere per la valutazione del rischio elettromagnetico in conformit? al D.Lgs. 81/2008. Pi? specificatamente gli obiettivi della campagna di misura sono stati i seguenti. Misura dei campi elettromagnetici (EM) in punti predefiniti per la determinazione dei livelli di campo EM presenti. Determinazione dei campi elettrici, magnetici ed elettromagnetici emessi da apparecchiature elettromedicali quali magnetoterapia e radarterapia . Misura dei campi magnetici (in particolare induzione magnetica) presenti nei locali tecnici quali cabina elettrica e impianti di condizionamento. Valutazione dell\u27intensit? dell\u27induzione magnetica all\u27interno e in prossimit? di incubatrici e culle termiche (Chiari e Iseo). Valutazione delle specifiche tecniche di elettrobisturi (Blocco Operatorio di Iseo). Caratterizzazione della presenza di eventuali interferenze EM dovute alla rete wireless (reparto di terapia intensiva di cardiologia di Chiari) o da disturbi EM presenti su apparecchiature per diagnostica (neurologia di Chiari)