Model order reduction for optimality systems through empirical gramians

In the present article, optimal control problems for linear parabolic partial differential equations (PDEs) with time-dependent coefficient functions are considered. One of the common approach in literature is to derive the first-order sufficient optimality system and to apply a finite element (FE) discretization. This leads to a specific linear but high-dimensional time variant (LTV) dynamical system. To reduce the size of the LTV system, we apply a tailored reduced order modeling technique based on empirical gramians and derived directly from the first-order optimality system. For testing purpose, we focus on two specific examples: a multiobjective optimization and a closed-loop optimal control problem. Our proposed methodology results to be better performing than a standard proper orthogonal decomposition (POD) approach for the above mentioned examples

Transcriptome Analysis of Canine Cutaneous Melanoma and Melanocytoma Reveals a Modulation of Genes Regulating Extracellular Matrix Metabolism and Cell Cycle

Interactions between tumor cells and tumor microenvironment are considered critical in carcinogenesis, tumor invasion and metastasis. To examine transcriptome changes and to explore the relationship with tumor microenvironment in canine cutaneous melanocytoma and melanoma, we extracted RNA from formalin-fixed, paraffin-embedded (FFPE) specimens and analyzed them by means of RNA-seq for transcriptional analysis. Melanocytoma and melanoma samples were compared to detect differential gene expressions and significant enriched pathways were explored to reveal functional relations between differentially expressed genes. The study demonstrated a differential expression of 60 genes in melanomas compared to melanocytomas. The differentially expressed genes cluster in the extracellular matrix-receptor interaction, protein digestion and absorption, focal adhesion and PI3K-Akt (phosphoinositide 3-kinase/protein kinase B) signaling pathways. Genes encoding for several collagen proteins were more commonly differentially expressed. Results of the RNA-seq were validated by qRT-PCR and protein expression of some target molecules was investigated by means of immunohistochemistry. We hypothesize that the developing melanoma actively promotes collagen metabolism and extracellular matrix remodeling as well as enhancing cell proliferation and survival contributing to disease progression and metastasis. In this study, we also detected unidentified genes in human melanoma expression studies and uncover new candidate drug targets for further testing in canine melanoma

Distribuzione del virus del tumore nasale enzootico in animali naturalmente infetti

Il tumore nasale enzootico è un adenocarcinoma contagioso a lento sviluppo che colpisce le prime vie respiratorie della capra e della pecora (1, 2, 3). L'agente eziologico è il retrovirus tipo-D denominato Enzootic nasal tumor virus (ENTV) il quale viene trasmesso orizzontalmente con il fluido nasale degli animali colpiti. ENTV è altamente correlato a Jaagsiekte Sheep Retrovirus (JSRV), agente causale dell'adenocarcinoma polmonare ovino, con cui condivide oltre il 95% del genoma e della struttura proteica (4). I meccanismi oncogenetici promossi da ENTV e le sue relazioni con quelli causati da JSRV non sono stati tuttavia sufficientemente chiariti

A Perspective of Coagulation Dysfunction in Multiple Sclerosis and in Experimental Allergic Encephalomyelitis

A key role of both coagulation and vascular thrombosis has been reported since the first descriptions of multiple sclerosis (MS). Subsequently, the observation of a close concordance between perivascular fibrin(ogen) deposition and the occurrence of clinical signs in experimental allergic encephalomyelitis (EAE), an animal model of MS, led to numerous investigations focused on the role of thrombin and fibrin(ogen). Indeed, the activation of microglia, resident innate immune cells, occurs early after fibrinogen leakage in the pre-demyelinating lesion stage of EAE and MS. Thrombin has both neuroprotective and pro-apoptotic effects according to its concentration. After exposure to high concentrations of thrombin, astrocytes become reactive and lose their neuroprotective and supportive functions, microglia proliferate, and produce reactive oxygen species, IL-1β, and TNFα. Heparin inhibits the thrombin generation and suppresses EAE. Platelets play an important role too. Indeed, in the acute phase of the disease, they begin the inflammatory response in the central nervous system by producing of IL-1alpha and triggering and amplifying the immune response. Their depletion, on the contrary, ameliorates the course of EAE. Finally, it has been proven that the use of several anticoagulant agents can successfully improve EAE. Altogether, these studies highlight the role of the coagulation pathway in the pathophysiology of MS and suggest possible therapeutic targets that may complement existing treatments

A Common Left Occipito-Temporal Dysfunction in Developmental Dyslexia and Acquired Letter-By-Letter Reading?

We used fMRI to examine functional brain abnormalities of German-speaking dyslexics who suffer from slow effortful reading but not from a reading accuracy problem. Similar to acquired cases of letter-by-letter reading, the developmental cases exhibited an abnormal strong effect of length (i.e., number of letters) on response time for words and pseudowords.Corresponding to lesions of left occipito-temporal (OT) regions in acquired cases, we found a dysfunction of this region in our developmental cases who failed to exhibit responsiveness of left OT regions to the length of words and pseudowords. This abnormality in the left OT cortex was accompanied by absent responsiveness to increased sublexical reading demands in phonological inferior frontal gyrus (IFG) regions. Interestingly, there was no abnormality in the left superior temporal cortex which--corresponding to the onological deficit explanation--is considered to be the prime locus of the reading difficulties of developmental dyslexia cases.The present functional imaging results suggest that developmental dyslexia similar to acquired letter-by-letter reading is due to a primary dysfunction of left OT regions

POD-based State-Constrained Economic Model Predictive Control of Convection-Diffusion Phenomena

Motivated by an application to energy efficient building, in this thesis optimal control of a linear time-dependent convection-diffusion equation is considered together with bilateral control and state constraints. To obtain regular Lagrange multipliers, two different approaches are investigated. The first one is called virtual control approach and it consists in introducing an artificial control, which allows replacing the pointwise state constraints with mixed constraints. The regularized problem is then solved with the Primal Dual Active Set Strategy (PDASS). The second applied technique is the augmented Lagrangian method: penalization terms dependent on the state constraints are added to the cost functional and many only control constrained problems are iteratively solved applying projected gradient or projected BFGS methods. To speed-up the computational time proper orthogonal decomposition (POD) is considered together with an a-posteriori error analysis, which ensures the quality of the POD approximation. Furthermore, model predictive control (MPC) helps to handle the long-time horizon and the problem parameter changes in an efficient way. At last, numerical simulations show the advantages and disadvantages of these techniques.publishe