Essays on governments, central banks, and credibility

In my PhD thesis I study the motivations, policy paths, and impacts of economic and political institutions in a number of different scenarios, employing a diverse range of methods and approaches. In Chapter 2 I explore the case of a central bank attempting to deal with a consumption externality created by external consumption habits by designing an application of a New Keynesian Dynamic Stochastic General Equilibrium model. In Chapter 3 I expand on the context of the previous Chapter to examine the possibility of a central bank setting monetary policy with a present bias, and what this means for the economy as a whole. Finally, in Chapter 4 I investigate the empirical patterns of political pressure on central banks on a global level. The main contributions of my PhD thesis are to shed more light on the consequences of external consumption habits in a context of discretionary monetary policy; to analyse the previously unexplored case of a central bank with a present bias; and to produce novel empirical findings on the topic of political pressure

Design of a flexible manufacturing cell/system, optimizing for quality

The research presented in this thesis is concerned with the Design of a FLEXIBLE MANUFACTURING CELL open to further expansion into FLEXIBLE MANUFACTURING SYSTEM. The work carried out includes practical and theoretical studies designed to meet the following objectives: PART ONE: - Presents the traditional design method used for the development of an FMC. PART TWO: - Presents an introduction to the formal " DESIGN FUNCTION DEPLOYMENT ", currently discussed at the Engineering Design Centre at the city University PART THREE: - Re-works the FMC design problem using the " DFD " methodology as currently exists. Presents the use of the " DFD " methodology with some additional features correlating modifications to costs. PART FOUR: - Presents the general conclusions about the FMC and its flexibility, and compares the design problem with and without DFD. Enhancements to the DFD methodologies are proposed. Where practicable, correlation between the results obtained from field experience and theoretical studies are attempted. The author intends the contents of this thesis to add to the existing knowledge of global design process and enable the identification of specific areas of work which should be pursued for further studies

Biochemical Signatures of Doppel Protein in Human Astrocytomas to Support Prediction in Tumor Malignancy

Doppel (Dpl) is a membrane-bound glycoprotein mainly expressed in the testis of adult healthy people. It is generally absent in the central nervous system, but its coding gene sequence is ectopically expressed in astrocytoma specimens and in derived cell lines. In this paper, we investigated the expression and the biochemical features of Dpl in a panel of 49 astrocytoma specimens of different WHO malignancy grades. As a result, Dpl was expressed in the majority of the investigated specimens (86%), also including low grade samples. Importantly, Dpl exhibited different cellular localizations and altered glycan moieties composition, depending on the tumor grade. Most low-grade astrocytomas (83%) showed a membrane-bound Dpl, like human healthy testis tissue, whereas the majority of high-grade astrocytomas (75%) displayed a cytosolic Dpl. Deglycosylation studies with N-glycosidase F and/or neuraminidase highlighted defective glycan moieties and an unexpected loss of sialic acid. To find associations between glial tumor progression and Dpl biochemical features, predictive bioinformatics approaches were produced. In particular, Decision tree and Nomogram analysis showed well-defined Dpl-based criteria that separately clustered low-and high-grade astrocytomas. Taken together, these findings show that in astrocytomas, Dpl undergoes different molecular processes that might constitute additional helpful tools to characterize the glial tumor progression

Pathological Pathways and Alpha-Synuclein in Parkinson's Disease: A View from the Periphery

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The Emerging Role of the Autophagy Process in Children with Celiac Disease: Current Status and Research Perspectives

Celiac disease (CD) affects approximately 1% of the population in Europe and North America, but the number of patients currently undiagnosed is estimated to be far higher than that of diagnosed cases owing to the presence of prevalent forms with nonspecific symptoms. The toxicity of gliadin in children with CD is not destroyed through digestion with gastropancreatic enzymes. An innate immunity to gliadin plays a key role in the development of CD. Autophagy, a physiological catabolic process, plays also a crucial role in the pathogenesis of several inflammatory diseases. Recent studies have described functional involvement of the regulation of autophagy within a pediatric CD cohort. Furthermore, the contribution of autophagy has been highlighted in the degradation and in the reduction of extracellular release of gliadin peptides, thus suggesting novel molecular targets to counteract gliadin-induced toxicity in CD

Gene Expression Analysis of an EGFR Indirectly Related Pathway Identified PTEN and MMP9 as Reliable Diagnostic Markers for Human Glial Tumor Specimens

In this study the mRNA levels of five EGFR indirectly related genes, EGFR, HB-EGF, ADAM17, PTEN, and MMP9, have been assessed by Real-time PCR in a panel of 37 glioblastoma multiforme specimens and in 5 normal brain samples; as a result, in glioblastoma, ADAM17 and PTEN expression was significantly lower than in normal brain samples, and, in particular, a statistically significant inverse correlation was found between PTEN and MMP9 mRNA levels. To verify if this correlation was conserved in gliomas, PTEN and MMP9 expression was further investigated in an additional panel of 16 anaplastic astrocytoma specimens and, in parallel, in different human normal and astrocytic tumor cell lines. In anaplastic astrocytomas PTEN expression was significantly higher than in glioblastoma multiforme, but no significant correlation was found between PTEN and MMP9 expression. PTEN and MMP9 mRNA levels were also employed to identify subgroups of specimens within the different glioma malignancy grades and to define a gene expression-based diagnostic classification scheme. In conclusion, this gene expression survey highlighted that the combined measurement of PTEN and MMP9 transcripts might represent a novel reliable tool for the differential diagnosis of high-grade gliomas, and it also suggested a functional link involving these genes in glial tumors

AUTOCOUNTER, an ImageJ JavaScript to analyze LC3B-GFP expression dynamics in autophagy-induced astrocytoma cells

An ImageJ JavaScript, AUTOCOUNTER, was specifically developed to monitor and measure LC3B-GFP expression in living human astrocytoma cells, namely T98G and U373-MG. Discrete intracellular GFP fluorescent spots derived from transduction of a Baculovirus replication-defective vector (BacMam LC3B-GFP), followed by microscope examinations at different times. After viral transgene expression, autophagy was induced by Rapamycin administration and assayed in ph-p70S6K/p70S6K and LC3B immunoblotting expression as well as by electron microscopy examinations. A mutated transgene, defective in LC3B lipidation, was employed as a negative control to further exclude fluorescent dots derived from protein intracellular aggregation. The ImageJ JavaScript was then employed to evaluate and score the dynamics changes of the number and area of LC3B-GFP puncta per cell in time course assays and in complex microscope examinations. In conclusion, AUTOCOUNTER enabled to quantify LC3B-GFP expression and to monitor dynamics changes in number and shapes of autophagosomal-like vesicles: it might therefore represent a suitable algorithmic tool for in vitro autophagy modulation studies

Inhibition of the Autophagy Pathway Synergistically Potentiates the Cytotoxic Activity of Givinostat (ITF2357) on Human Glioblastoma Cancer Stem Cells

Increasing evidence highlighted the role of cancer stem cells (CSCs) in the development of tumor resistance to therapy, particularly in glioblastoma (GBM). Therefore, the development of new therapies, specifically directed against GBM CSCs, constitutes an important research avenue. Considering the extended range of cancer-related pathways modulated by histone acetylation/deacetylation processes, we studied the anti-proliferative and pro-apoptotic efficacy of givinostat (GVS), a pan-histone deacetylase inhibitor, on cell cultures enriched in CSCs, isolated from nine human GBMs. We report that GVS induced a significant reduction of viability and self-renewal ability in all GBM CSC cultures; conversely, GVS exposure did not cause a significant cytotoxic activity toward differentiated GBM cells and normal mesenchymal human stem cells. Analyzing the cellular and molecular mechanisms involved, we demonstrated that GVS affected CSC viability through the activation of programmed cell death pathways. In particular, a marked stimulation of macroautophagy was observed after GVS treatment. To understand the functional link between GVS treatment and autophagy activation, different genetic and pharmacological interfering strategies were used. We show that the up-regulation of the autophagy process, obtained by deprivation of growth factors, induced a reduction of CSC sensitivity to GVS, while the pharmacological inhibition of the autophagy pathway and the silencing of the key autophagy gene ATG7, increased the cell death rate induced by GVS. Altogether these findings suggest that autophagy represents a pro-survival mechanism activated by GBM CSCs to counteract the efficacy of the anti-proliferative activity of GVS. In conclusion, we demonstrate that GVS is a novel pharmacological tool able to target GBM CSC viability and its efficacy can be enhanced by autophagy inhibitory strategies

Fatores epidemiológicos Ro e Re durante a COVID-19: o que eles são e como diferem?

Infectious diseases are those caused by pathogenic microbes such as some bacteria, viruses, parasites, among others. These diseases can be transmitted, directly or indirectly, from one individual to another 1. Epidemiology studies the health and disease processes that affect populations. It is interested in knowing the characteristics of the groups that are affected; how health and disease events are distributed geographically and over time; how often they manifest themselves and what are the causes or factors associated with their emergence 2. How to cite this article: Comincini Cantillo Eric, Wilches Visbal Jorge Homero, Saraví Fernando Daniel. Factores epidemiológicos R0 y Re durante la COVID-19: ¿qué son y en qué difieren?.   Revista Cuidarte. 2021;12(1):e1290. http://dx.doi.org/10.15649/cuidarte.1290     Las enfermedades infecciosas son aquellas causadas por microbios patógenos como algunas bacterias, virus, parásitos, entre otros. Estas enfermedades pueden transmitirse, directa o indirectamente, de un individuo a otro 1. La epidemiología estudia los procesos de salud y enfermedad que afectan a las poblaciones. Se interesa por conocer las características de los grupos que se ven afectados; cómo se distribuyen geográficamente y en el tiempo los eventos de salud y enfermedad; con qué frecuencia se manifiestan y cuáles son las causas o factores asociados a su surgimiento 2. Como citar este artículo: Comincini Cantillo Eric, Wilches Visbal Jorge Homero, Saraví Fernando Daniel. Factores epidemiológicos R0 y Re durante la COVID-19: ¿qué son y en qué difieren?.   Revista Cuidarte. 2021;12(1):e1290. http://dx.doi.org/10.15649/cuidarte.1290     As doenças infecciosas são aquelas causadas por micróbios patogénicos como algumas bactérias, vírus, parasitas, entre outros. Estas doenças podem ser transmitidas, directa ou indirectamente, de um indivíduo para outro 1. A epidemiologia estuda os processos de saúde e doença que afectam as populações. Está interessado em conhecer as características dos grupos afectados; como os eventos de saúde e doença são distribuídos geograficamente e ao longo do tempo; com que frequência ocorrem; e quais são as causas ou factores associados ao seu aparecimento 2. Como citar este artigo: Comincini Cantillo Eric, Wilches Visbal Jorge Homero, Saraví Fernando Daniel. Factores epidemiológicos R0 y Re durante la COVID-19: ¿qué son y en qué difieren?.   Revista Cuidarte. 2021;12(1):e1290. http://dx.doi.org/10.15649/cuidarte.1290    &nbsp