Il linguaggio della satira a Modena Materiali per una storia dell’illustrazione umoristica tra Otto e Novecento

The node’s specific test of Modena’s illustrated comics, in the late nineteenth century and the first two decades of the twentieth century, made it possible to add new tiles of knowledge in an already existing historiography on the subject, drawing a historical framework in which the Modena’s illustration developed itself, both in reference to an urban context and beyond this. The complete photographic campaign has offered the opportunity to enhance documents with the result of new assignments. This led to the reorganization of the acquired data, as well as the deepening of the individual personality, highlighting aspects so far remained in the shadows. By the analysis performed, signs of major innovations emerged from the "Marchese Colombi" of 1893 and "La Sciarpa d’Iride" in 1897, so that they can be considered essential in Modena’s publishing publications in the specific field of illustrated comics. The first new feature is the collaboration of Umberto Tirelli to "Marchese Colombi" which, starting from 1895, brings the cartoon image to become the central node of the journal despite the text, this prerogative recognized by most critics as the the exclusive "Duca Borso" since 1900. In the assignment test has been recognized Umberto Tirelli as the author of cartoons traced in several sheets appeared between 1900 and 1903; in some cases, these partnerships were simply reordered, in others, we can talk of new assignments. Furthermore, from the analysis of fifteen years of "Duca Borso," it was possible to reconsider the common opinion of the critics, on the basis that the most prosperous period and lush of the magazine coincides with the direction of Umberto Tirelli. Between 1908 and 1912, in fact, on "Duca Borso" interesting illustrations of artists no less valid Tirelli are alternated, and yet, in the last two years of life, very young designers collaborate and such practice will herald them painting experience. It is found in these pages the figure of sixteen years old Mario Vellani Marchi identified under the pseudonym of Marius, in which has been tried to reconstruct a biographical profile as update as possible. Special attention has also been devoted to the Unique Numbers and to periodicals discontinuously issued, among which we remember "Il Navicello” on 8 May 1910, whose illustrations were attributed to the illustrator Aguini, who stole them from Umberto Tirelli. The catalog of Aguini has been enriched also by illustrations of other Unique Numbers appeared in Modena until 1913. After the break imposed by the war, the humorous illustration will be entrusted in its results in particular to Mario Vellani Marchi which, in 1921, along with Casimiro Jodi will establish "Il Gatto Bigio." Mario Vellani Marchi is the first artist that contributed to the developments of Modena’s illustrated comics during the twenties

PROCEDURA PER IL RICONOSCIMENTO DELLE UNITA’ ELEMENTARI NEGLI AGGREGATI URBANI ATTRAVERSO LA COMPRENSIONE DEI PROCESSI TIPOLOGICI

Seismic events in recent years have caused heavy damage to historic city centers. This calls for an effective planning aimed at reaching an adequate decrease of the vulnerability of city centers buildings. A deep knowledge of the structure of the urban environment ‐ and, to a lesser extent, of the buildings the urban environment is made up of ‐ is the essential precondition for effectively intervening on the urban fabric. Currently, the most used means of knowledge are Vulnerability Assessment Forms, whose goal is to assess not only the damage suffered by a building in the aftermath of an earthquake, but also its habitability standards. These forms, which are supposed to assess the buildings as a whole, in most cases only analyzes single buildings or cadastral units, since there is no well‐defined procedure on how to identify single units within the urban fabric. The identification of an Elementary Unit (i.e. the smallest independent unit within the fabric) is the crucial point of this delicate process. This identification process, though, is based on weak and misleading definitions, e.g. those that have been used up to today to fill in the Assessment Forms. This work of research aims at clearly defining both the idea itself of Elementary Unit and a procedure to identify it. This procedure could be extensively used not only in emergency situations, but also for the regular preventive territory management. This goal can be reached through a constant phenomenological examination of the urban fabric buildings carried out using Muratori‐inspired typological analysis tools. By studying the transformation process of the basic building types, it is possible to identify the Elementary Units the urban fabric is made up of. Once the urban fabric structure has been comprehended, this work will present a clear and most valid definition of Elementary Unit, which will simplify any later examination of the urban fabric – from the identification of “subjects” for AeDES Forms, to the drafting of Reconstruction Plans. The case study of Ferrara offers a chance to verify the validity of the process of identification of buildings within the urban fabric, designed on a real example. This will, in turn, prove the validity of the term “Elementary Unit” and its strong connection with the concept of building type and the typological development

MicroRNA-Based Therapeutics in Hepatocellular Carcinoma: In Vitro and in Vivo Studies

Hepatocellular carcinoma (HCC) is a serious public health problem, without an effective cure. It has been demonstrated that the deregulation of microRNAs expression contribute to tumorigenesis. In HCC, miR-221 was shown to be up-regulated in more than 70% of the cases and was associated with higher tumor stage, metastasis and a shorter time to recurrence after surgery. A tumor promoting function of miR-221 was proved in a transgenic mouse model, which was predisposed to the development of liver cancers. These findings suggested that miR-221 could represent a potential target for anti-tumor approaches. Conversely, miR-199a is of interest because its level was shown to be reduced in almost 100% of HCC, it was significantly correlated with poor prognosis and was shown to target c-Met, an oncogene involved in invasion and metastasis. In the present thesis, novel Adenoviruses and Adeno-Associated viral vector (AAVVs) were developed. They were genetically modified to drive the expression of multiple binding sites for miR-221, the “miR-221 sponge”, as well as miRNA precursor for miR-199a. Analysis of miR-221 sponge in HCC cells revealed the capability to reduce miR-221 endogenous levels, which was accompanied by an increase in CDKN1B/p27 protein, a known target of miR-221. An increase in apoptosis was detected in Hep3B cells after infection with any of adeno or AAVs in comparison with control viruses. Moreover, restoring the level of miR-199a could also reduce viability and increase apoptosis of HepG2 cells. Therapeutic efficacy of miR-221 antisense oligonucleotides and a tumor suppressive role of miR-199a alone or in combination with sorafenib were also evaluated. We showed that combining an antimiR-221/mimic miR-199a with sorafenib improves the response of HCC cells to molecular targeted treatment through enhancing the inhibition of cell proliferation and induction of apoptosis and arresting the cell cycle in G1. To validate the therapeutic potential of miR-199a, we demonstrated that in vivo delivery of miR-199a oligonucleotide leads to a reduction of the number and size of tumor nodules as sorafenib, without any apparent toxicity. This study showed that methods for modulating microRNA activities could elicit measurable anti-tumor effects, that deserve further study to improve existing therapies

Molecular cocrystals of pharmaceutical interest

Crystal form (cocrystals, polymorphs, salts, hydrates and solvates) assortment remains a scientific challenge that implicates practical issues in the pharmaceutical industry at the late stage of drug development of pharmaceutical formulations and in early stage of synthesis and isolation of an API in favorable defined crystalline form. Indeed, the selection of the optimal crystal form of an API that indisputably impacts the drug development program is directly related to the API’s aqueous solubility. Since the aqueous solubility of an API is the benchmark for its drug delivery and absorption, by crystal form screening, optimization and selection it is possible to control the dissolution rate of API, and thus to determine the extent of its bioavailability and pharmacokinetics profile which are intricately interrelated to solubility and crystal forms. Therefore, understanding the crystal packing forces and their impact upon physicochemical properties of different crystal forms is threshold for controlling the performance of the API. The array of crystal forms in which molecular crystal of API may exist prevails over its possible polymorphs, salts, solvates and hydrates due to the vast number of potential coformers which, not only extend over the limited counterions for salt formation, but also they are much more versatile in nature and thus imply for more complex intermolecular interactions based on different H-bonding with API that lead to conformational changes and flexibility for crystal packing in process of cocrystallization. Molecular crystals of pharmaceutical interest are amenable to excel the phase transition in API which exert polymorphism. But on the other hand, due to the conformational flexibility caused by intermolecular recognition based on hydrogen bonding, they exploit the new polymorphic forms of the API that might be stabilized in the presence of favorable selected coformers. Another benefit of the molecular crystals cocrystalized with appropriate coformers is controlling the stereoselective resolution of the racemic APIs. The concept of modifying the properties of the API by the forming the molecular crystals containing single API in combination with coformer that is another API or functional excipient that improves the performance of the drug delivery or in the formulations, compared to the native API crystal, has become emerging paradigm for drug development programs. Moreover the combination of fixed-doses formulation have been frequently prescribed for therapy, the multi-API or “drug-drug” molecular crystals are relatively unexploited solid forms of APIs. This molecular crystals cocrystallized of the different by nature API, but complementary in terms of pharmacological effect or their mechanism of action have potential relevance for improving the physicochemical properties of both APIs, their biopharmaceutical performance and synergy in pharmacological respond. Crystal form screening of metformin yields two groups of molecular salts. The one comprises the molecular salts of metformin with a wide range of organic acids recognized as safe for food additives, the other is referred to molecular salts of metformin cocrystallized with coformers which are APIs (diclofenac, dichloroacetic acid, glycolic acid, and salicylic acid) and functional excipients (saccharin and acesulfame). Preliminary testing of cytotoxicity of the molecular crystals of metformin with dicloroacetic acid indicate an increased anticancer effect comparing to the effect exerted by the native drugs.

Optimization Methods for Image Regularization from Poisson Data

This work regards optimization techniques for image restoration problems in presence of Poisson noise. In several imaging applications (e.g. Astronomy, Microscopy, Medical Imaging) such noise is predominant; hence regularization techniques are needed in order to obtain satisfying restored images. In a variational framework, the image restoration problem consists in finding a minimum of a functional, which is the sum of two terms,: the fit–to–data and the regularization one. The trade–off between these two terms is measured by a regularization parameter. The estimation of such a parameter is very difficult due to the presence of Poisson noise. In this thesis we investigate three models regarding this parameter: a Discrepancy Model, Constrained Model and the Bregman procedure. The former two provide an estimation for the regularization parameter, but in some cases, such as low counts images, they do not allow to obtain satisfactory results. On the other hand, in presence of such images the Bregman procedure provides reliable results and, moreover, it allows to use an overestimation of the regularization parameter, giving satisfying restored images; furthermore, this procedure permits to gain a contrast enhancement on the final result. In the first part of the work, the basics on image restoration problems are recalled, and a survey on the state–of–the–art methods is given, with an original contribution regarding scaling techniques in ε–subgradient methods. Then, the Discrepancy and the Constrained Models are analyzed from both theoretical and practical point of view, developing suitable numerical techniques for their solution; furthermore, an inexact version of the Bregman procedure is introduced: such a version allows to have a minor computational cost and maintains the same theoretical features of the exact version. Finally, in the last part, a wide experimentation shows the computational efficiency of the inexact Bregman procedure; furthermore, the three models are compared, showing that in high counts images they provide similar results, while in case of low counts images the Bregman procedure provides reliable restored images. This last consideration is evident not only on test problems, but also in problems coming from Astronomy imaging, particularly in case of High Dynamic Range images, as shown in the final part of the experimental section

Managing Cancer and Living Meaningfully (CALM): Application in Italy of an Innovative Meaning-Centered Intervention for Advanced Cancer Patients

Background: Managing Cancer and Living Meaningfully psychotherapy (CaLM) is an innovative approach aimed at reducing depression and demoralization in advanced cancer patients, while promoting meaning making processes and personal growth. These constructs are considered to be the principal components at the basis of existential distress or vice versa, of a sense of meaning and fulfillment at the end of life. The aim of this research was to investigate the acceptability and feasibility of CaLM within an Italian context, while evaluating its potentiality of reducing depression, demoralization, anxiety and other emotional distress as compared to controls treated with usual care (UC). Materials and Methods: Advanced cancer patients were randomized to be allocated either in the experimental arm to receive a semi-structured intervention of 12 individual sessions delivered over 6 months; or in a control arm to receive UC at the hospital Oncology Service. Usual care included routine oncology clinic visits, during which distress screening was carried out. The primary expected outcomes were greater improvements of depression (at PHQ-9), and demoralization (at Demoralization Scale). Secondary outcomes included greater positive changhes anxiety (at DADDS), spiritual wellbeing (at FACIT), quality of life (at QUAL-EC) and posttraumatic growth (at PTGI).in experimental arm vs controls. At 3 and 6 months CaLM participants were interviewed about their therapy experience and both CaLM and UC patients were administered a questionnaire assessing satisfaction with care. Results: Statistical analysis indicated that experimental group patients had a significant improvement in important clinical aspects of existential distress, including depression, demoralization, and anxiety. Moreover they experienced a higher spiritual well-being and a post-traumatic growth as a result of CaLM therapy. UC patients did not present any statistically significant change. Qualitative analysis of the experimental group comments on the intervention underscored CaLM benefits, including an increased awareness and involvement in life. Conclusions: The findings of our study demonstrated a full acceptability and feasibility of CaLM intervention, while indicating its effectiveness in reducing existential distress and promoting psychological and spiritual growth in advanced cancer patients

CANNABINOID CB2 AND μ-OPIOID RECEPTORS SIGNALLING IN MICROGLIAL CELLS: POTENTIAL TARGETS TO INCREASE CLINICAL EFFICACY OF OPIOIDS

Among several pharmacological properties, analgesia is the most common feature shared by either opioid or cannabinoid systems. In the nervous system, neurotransmission and neuroinflammation are mediated by the endocannabinoid signalling system. Two subtypes of the mammalian cannabinoid receptors, CB1 and CB2, have been identified. Opioids produce their pharmacological effects by acting mainly through three types of receptors, namely μ, δ and κ. Anti-nociceptive tolerance to opioids severely limits their clinical efficacy for the treatment of chronic pain syndromes. It has been demonstrated that glia has a central role in the development of morphine tolerance. Microglia, a specialized population of macrophages found in the CNS, are quiescent in normal brain. However, after CNS injury these cells can be activated by cytokines produced by infiltrating immune effector cells. Interestingly, receptors for opioids and cannabinoids are coupled to similar intracellular signalling mechanisms leading to a decrease in cAMP production through the activation of Gi proteins. Therefore, following the discovery that opioids and cannabinoids produce not only similar biochemical effects but also similar pharmacological effects, the interaction between these two classes of drugs has been extensively studied. In the present study, at first we characterized the signal transduction pathways affected by CB2 receptors in quiescent and activated murine microglia. Our results demonstrated that CB2 receptors stimulation, through MAPK pathway modulation, may promote anti-inflammatory responses in activated microglia. Next, we investigated whether and how CB2 receptor stimulation affected opioid actions on activated microglia. The results indicate that morphine increases PKCε expression and activation and stimulates Akt pathway upstream of ERK1/2 and iNOS in activated microglia. Furthermore, we found that morphine enhanced the release of IL-1β, TNF-α, IL-6 and of NO via μ- opioid receptor-PKCε signalling pathway in activated microglial cells, mediating a proinflammatory phenotype in mouse microglial cells. Interestingly, CB2 receptor stimulation attenuated morphine-induced microglial proinflammatory mediator increases, interfering with morphine action by acting on the Akt-ERK1/2 signalling pathway. Because glial activation opposes opioid analgesia and enhances opioid tolerance and dependence, we suggest that CB2 receptors, by inhibiting microglial activity, may be potential targets to increase clinical efficacy of opioids

Effetto dell’ivabradina nelle fasi iniziali e nella progressione dell’aterosclerosi

Effect of ivabradine in the initial steps and in the progression of the atherosclerosis Purpose: Ivabradine reduces heart rate (HR) by selectively inhibiting the If current in the sinus node. A sub-group of the BEAUTifUL study showed that ivabradine reduces the incidence of myocardial infarction in coronary artery disease (CAD) patients with HR ≥ 70bpm, suggesting a protective effect on the arterial wall. The SIGNifY study is currently testing this hypothesis in more than 19000 CAD patients. In dyslipidaemic mice, ivabradine improves vascular function and reduces aortic plaques area. It has been suggested that ivabradine may exert a protective activity by decreasing low/oscillatory shear stress, which is proinflammatory in the endothelium. This study aims to determine if HR reduction with ivabradine induces an atheroprotective gene expression profile in the endothelium of dyslipidaemic mice before plaque formation. Methods: 6 week-old ApoE deficient mice (n=6), fed a chow diet, were treated with ivabradine (30 mg/Kg/day, in drinking water) for 2 or 4 weeks. Two control groups (n=6) received no ivabradine. Ivabradine reduced HR by 17.4% and 22.9% in mice treated for 2 weeks and 4 weeks respectively. At the end of treatment, endothelium-enriched RNA was isolated from the aortic arch. Gene expression was analyzed by Agilent Whole Mouse Gene Expression Microarray (60k probes). Pathway analysis was performed using DAVID tools. Principal components analysis showed that most of the variability in gene expression can be attributed to ivabradine treatment and was independent of treatment duration. Differentially expressed genes were selected as having a ≥ 1.5-fold expression difference between treated and untreated groups with a p-value ≤ 0.01 at unpaired t-test. Results: Treatment induced changes in the expression of 930 transcripts. Shear stress-modulated pathways such as MAPK signalling and steroid biosynthesis process (both inhibited by treatment) were among the most significantly affected pathways (p-value = 0.0065 and 0.0009, respectively). We found up-regulation of anti-inflammatory genes and down-regulation of pro-apoptotic and pro-inflammatory genes, the majority of which were NF-kappa B and/or Ang II-regulated genes. Among them, the receptor for oxidized lipoprotein (Olr1) was strongly downregulated (3.2 fold). Conclusions: In dyslipidaemic mice, short term treatment with ivabradine induces an atheroprotective gene expression profile in the endothelium. Since many of the affected genes are shear stress regulated, our data suggest that shear stress frequency modulation could be part of the molecular mechanisms by which ivabradine protects the endothelium

An insight into the role of magnetic anisotropies in the behavior of thin films and arrays of nanoparticles

In this thesis work we discussed the properties of magnetic materials derived by the reduction of at least one of the spatial dimensions under the micrometer scale: in particular we analyzed the origin of some magnetic behaviors in magnetic nanostructures like thin films and arrays of nanodots. One of the important properties which is strongly affected by the size reduction and in which is contained most of the physical description of a magnetic system is the anisotropy energy term: a direction-dependent parameter which strongly contributes to the determination of the equilibrium state and magnetic behavior. We described various nanostructured systems concentrating prevalently on thin films and arrays of interacting nanoparticles and for each system the origin and the physical implications of magnetic anisotropy is discussed. In thin magnetic films, two types of magnetic anisotropies are presented: Perpendicular Magnetic Anisotropy which has a crystalline origin and competes with the shape anisotropy of the thin film producing a singular type of magnetic domains called “stripes” and the Rotatable Anisotropy (the easy magnetic direction is not fixed but could be rotated by means of an external magnetic field). We tried to give a better explanation and modeling of the Rotatable Anisotropy, making a parallelism between the static and dynamic experimental evidences. We performed also a description of the interaction of magnetic dots in arrays with different symmetry and with finite dimensions. In particular we discovered a peculiar space-dependent behavior that we called “Global Configurational Anisotropy”, that has a strong importance when the dimension of the array becomes comparable with the dimension of the nanoparticles