Archivio istituzionale della ricerca - Università dell'Insubria
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GLT-based numerical solvers for Fractional Differential Equations
Get PDFFractional differential equations are powerful, versatile models for a wide range of real-world phenomena and are commonly used in many applicative fields. On the downside, analytical solutions are often unavailable or difficult to acquire and handle, while their discretization leads to large, dense, and ill-conditioned linear systems, hard to treat computationally.
This Thesis explores the development of numerical methods within the framework of Generalized Locally Toeplitz (GLT) matrix sequences. By using GLT theory to analyze the eigenvalues and singular values of the coefficient matrix sequences, we construct efficient and accurate solvers for various multi-dimensional fractional differential equations, including Krylov and multigrid methods for diffusion equations defined on general convex domains, as well as preconditioning techniques for equations involving the fractional Laplacian. In each scenario, we highlight both the peculiarities characterizing the specific problem and general aspects that may be applied in other contexts, testing the theoretical results through several numerical experiments.Fractional differential equations are powerful, versatile models for a wide range of real-world phenomena and are commonly used in many applicative fields. On the downside, analytical solutions are often unavailable or difficult to acquire and handle, while their discretization leads to large, dense, and ill-conditioned linear systems, hard to treat computationally.
This Thesis explores the development of numerical methods within the framework of Generalized Locally Toeplitz (GLT) matrix sequences. By using GLT theory to analyze the eigenvalues and singular values of the coefficient matrix sequences, we construct efficient and accurate solvers for various multi-dimensional fractional differential equations, including Krylov and multigrid methods for diffusion equations defined on general convex domains, as well as preconditioning techniques for equations involving the fractional Laplacian. In each scenario, we highlight both the peculiarities characterizing the specific problem and general aspects that may be applied in other contexts, testing the theoretical results through several numerical experiments
The first specimen with skin preserved of Lariosaurus (Eusauropterygia) from the Middle Triassic of Monte San Giorgio (Switzerland) allows inferences about its swimming method
No full textA new virtually complete specimen of the eosauropterygian nothosauroid Lariosaurus valceresii is described. The
specimen was collected in the Kalkschieferzone of the Meride Limestone (Ladinian, Middle Triassic) in the UNESCO
World Heritage area of Monte San Giorgio (Switzerland/Italy). The new specimen is the first L. valceresii collected
in Switzerland and the first known Lariosaurus specimen with remains of the skin. The skin is preserved as a carbon
film revealing the shape of the scales. It outlines the body and limbs, showing that the hands and feet were webbed.
The skin is present postaxial to both the humeral shafts and the anterior portion of the trunk suggesting the possible
presence in life of large and very strong retractor muscles for the forelimbs indicative that Lariosaurus could have
performed a paraxial, otariid-like, "flying-rowing" swimming for rapid acceleration
EGFR-Targeted Photodynamic Treatment of Triple Negative Breast Cancer Cell Lines Using Porphyrin–Peptide Conjugates: Synthesis and Mechanistic Insight
No full textTriple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by the absence of estrogen receptor, progesterone receptor, and human epidermal
growth factor receptor 2, limiting the efficacy of conventional targeted therapies. As a
result, novel therapeutic strategies are urgently needed. Photodynamic therapy (PDT),
which relies on the activation of photosensitizers (PSs) by light to induce cytotoxic effects,
has emerged as a promising alternative for TNBC treatment. Furthermore, the conjugation
of PSs with targeting peptides has demonstrated enhanced selectivity and therapeutic
efficacy, particularly for porphyrin-based photosensitizers. In this study, we report the synthesis of novel porphyrin–peptide conjugates designed to selectively target the epidermal growth factor receptor (EGFR), which is frequently overexpressed in TNBC. The conjugates were prepared via thiol displacement of the meso-nitro group in a 5,15-diarylporphyrin scaffold using EGFR-binding peptides. Photodynamic activity was evaluated in two EGFRoverexpressing TNBC cell lines. Cellular uptake of the conjugates correlated with EGFR expression levels, and PDT treatment resulted in differential induction of necrosis, apoptosis, and autophagy. Notably, the conjugates significantly inhibited EGFR-expressing
cell line migration, a critical hallmark of metastatic progression. These findings underscore the potential of EGFR-targeted porphyrin–peptide conjugates as promising PDT agents for the treatment of TNBC
Ultrastructural Aspects of Physiological Mineralization: A Comparative Study in Different Hard Tissues
Get PDFThe calcified tissues of vertebrates are essentially represented by bone, cartilage, dentin and calcified tendons. In all these tissues a major hallmark of mineralization is the deposition of the inorganic phase on a pre-existing collagen template, but evident differences exist among these materials and the molecular details of the process are still incompletely understood. In this study, the ultrastructural aspects of the mineral phase of these tissues were investigated by means of high-resolution scanning electron microscopy (HR-SEM) after low-temperature thermal deproteination, a technique allowing a direct, unrestricted visualization of the mineral component. Each tissue showed distinctive features. In most cases, calcification proceeds in a discontinuous way through the formation of clumps or clusters of mineralized tissue; in all cases, except cartilage, the mineral phase shows an evident relationship with the layout and/or the D-period of the collagen fibrils. Our results highlight the peculiar aspect of the mineralization process in the cartilage with respect to the other tissues, all of them containing collagen type I instead of type II, and suggest that a different molecular mechanism may be at work. It is still unclear whether and how this may be related to the content, exclusive of cartilage, of collagen type II. The identification of the tissue-specific features exhibited by cartilage versus those shared by all the other three tissues, although from different species, requires further research on physiological calcification
TMEM219 signaling promotes intestinal stem cell death and exacerbates colitis
Get PDFMechanisms by which mucosal regeneration is abrogated in inflammatory bowel disease (IBD) are still under investigation, and a role for an intestinal stem cell (ISC) defect is now emerging. Herein, we report an abnormal ISC death that occurs in Crohn's disease, which exacerbates colitis, limits ISC-dependent mucosal repair, and is controlled through the death factor Transmembrane protein 219 (TMEM219). Large alterations in TMEM219 expression were observed in patients with Crohn's disease, particularly in those with active disease and/or those who were nonresponders to conventional therapy, confirming that TMEM219 signaling is abnormally activated and leads to failure of the mucosal regenerative response. Mechanistic studies revealed a proapoptotic TMEM219-mediated molecular signature in Crohn's disease, which associates with Caspase-8 activation and ISC death. Pharmacological blockade of the IGFBP3/TMEM219 binding/signal with the recombinant protein ecto-TMEM219 restored the self-renewal abilities of miniguts generated from patients with Crohn's disease in vitro and ameliorated DSS-induced and T cell-mediated colitis in vivo, ultimately leading to mucosal healing. Genetic tissue-specific deletion of TMEM219 in ISCs in newly generated TMEM219fl/flLGR5cre mice revived their mucosal regenerative abilities both in vitro and in vivo. Our findings demonstrate that a TMEM219-dependent ISC death exacerbates colitis and that TMEM219 blockade reestablishes intestinal self-renewal properties in IBD
A Replicated Study on Factors Affecting Software Understandability
No full textBackground. Understandability is an important characteristic of software code that can largely impact the effectiveness and cost of software maintenance.
Aim. We investigate if and to what extent the characteristics of source code captured by static metrics affect understandability.
Method. We replicated an empirical study which provided some insights and highlighted some code characteristics that seem to affect understandability. The replication took place in a different country and was conducted with a different set of developers, i.e., Bachelor’s students, instead of Master’s students. The same source code was used in both studies.
Results. The data collected in the replication do not corroborate the results of the initial study, since no correlation between code measures and code understanding could be found. The reason seems to be that the initial study involved developers with very similar skills and experience, while the replication involved developers with quite different skills.
Conclusions. Code understanding appears to be affected much more by developers’ skills than by code characteristics. The extent to which code understanding depends on code characteristics is
observable only for a homogeneous population of developers. Our results can be useful for software practioners and for future software understandability studies
Assessment of asbestos exposure in Kyrgyzstan through analysis of raw and processed materials, air samples and human lung tissue
Get PDF: Asbestos still represents a major public health problem on a global scale. In Central Asia chrysotile is still mined and used, claiming that it is safer with respect to amphibole asbestos within certain concentrations. However, the problem of asbestos exposure in Central Asia and its consequences on human health have been poorly investigated. We analysed, for the first time, samples of raw and wrought material coming from one of the two asbestos-cement industries, currently active, located near the city of Bishkek, the capital of Kyrgyzstan, as well as air samples collected on different sites of Bishkek and Kant and lung tissues taken from the general population during clinical autopsies. Air samples have been analyzed using a scanning electron microscopy (SEM) equipped with energy dispersive spectroscopy (EDS). Heavy air asbestos pollution was detected in Kant (30.2 ff/L), while Bishkek had lower levels. Lung tissue analysis in the general population, carried out using both SEM and transmission electron microscopy (TEM) with EDS, revealed the presence of both chrysotile and amphibole asbestos. Such findings underline that, even in countries where the use of asbestos is allowed based on the presumed pureness of chrysotile used and the lower carcinogenic potential of chrysotile compared to amphibole asbestos, the general population could be exposed also to amphibole asbestos
Unravelling the Effect of Sediment Properties on As(V) and As(III) Adsorption/Desorption Processes: Implications for Groundwater Geochemistry
No full textArsenic (As) mobility in aquifer systems is mainly governed by its adsorption and desorption behaviour at the sediment-water interface, directly influencing its environmental availability and risks to water quality. This study explores the adsorption-desorption behaviour of inorganic As species through batch experiments on environmental sediments collected from three representative depths, selected to reflect local contrasting geochemical, mineralogical, and granulometric characteristics of the Como basin aquifer (Northern Italy). This setting was selected as a case study owing to its notable gradient in As concentration in groundwater: the shallow aquifers host concentrations typically below 10 μg/L, while the deep aquifer reaches concentrations of about 250 μg/L. Statistical analyses (ANOVA and simple linear regression) identified Mn- and Al-(hydr)oxide content, grain size, and mineralogy as strong predictors of As(V) retention, whereas As(III) showed no significant correlation with individual sediment properties within the tested conditions. Shallow, Mn- and Al-rich sediments exhibited higher adsorption capacity and corresponded to lower dissolved As in groundwater, while deeper, finer-grained sediments with lower oxide content coincided with elevated groundwater As concentrations. Desorption experiments indicated that As(III) dominated the released fraction, reflecting its greater mobility under variable pH and redox aquifer conditions. These results provide mechanistic insight into sediment-water interactions controlling As distribution in multilayer aquifers, supporting improved risk assessment and management of As in complex groundwater systems