University of Udine
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La plurisoggettività nell’agire colposo. Una rilettura in chiave normativa
No full textLa responsabilità per colpa si manifesta sempre più spesso nella forma dell’agire plurisoggettivo, al punto di far apparire come recessiva l’imputazione a titolo monosoggettivo. Le particolarità della plurisoggettività della colpa suggeriscono l’abbandono delle concezioni “unitarie” della concorsualità, a favore di un’impostazione che privilegi il carattere normativo della colpa come sua base ricostruttiva
Comparative analysis of methods for estimating genetic parameters of fruit-quality traits in apple breeding program
Get PDFApples, originating from Central Asia, are widely cultivated worldwide, with China producing 47.6 million tonnes annually. Despite their global importance, breeding programs often focus on a limited number of high-quality cultivars, potentially threatening genetic diversity. To mitigate this risk, advanced statistical methods could be employed to improve selection strategies. For example, the multi-trait BLUP method, which accounts for genetic correlations among traits, can reduce selection bias but increases computational complexity due to the model’s intricacy and slow convergence of the REML process. Bayesian methods, like Markov Chain Monte Carlo (MCMC), offer a solution to these challenges. This study compares single-trait and multi-trait approaches using REML/BLUP and MCMC/BLUP to estimate variance components and predict genetic values. Over two seasons, phenotypic data from 304 seedlings and 16 parents were analyzed using an animal model to predict their genetic values related to fruit quality traits. Significant progress was made in estimating genetic parameters and selecting parents for traits such as fruit weight, flesh firmness, and soluble solids content in the University of Udine’s apple breeding program. The multi-trait BLUP method improved the accuracy of predicted breeding values, particularly for fruit weight, polar diameter, flesh firmness, and soluble solids content. The multivariate repeated measures model, despite low correlations between some trait pairs, was recommended for integrating multi-season results and accounting for trait correlations. The Bayesian MCMC approach proved superior in genetic evaluations, offering higher heritabilities and genetic gains compared to Fisherian methods (REML). It effectively handles small sample sizes, captures more genetic variance, and enhances breeding value predictions, recommending traits like fruit size, firmness, and sweetness for selecting superior parents
Molecular simulations of platinum-based anticancer drugs interacting with potential drug delivery systems
No full textIn therapidlyevolvingfieldofdrugdelivery,computationalmethodssuchas
molecular dynamics(MD)simulationshavebecomeindispensabletoolsforun-
derstanding complexinteractionsatthemolecularlevel.ThisthesisusesMD
to investigatetheadsorptionbehaviorandinteractionsofplatinum-basedan-
titumor agentswithnanoscaledrugdeliverysystems,focusingontwodistinct
nanovehicles:grapheneandhumanserumalbumin(HSA).Thesesystemsrep-
resentcomplementaryapproachesinnanomedicine,withgrapheneknownfor
its extraordinaryadsorptioncapacityduetoitshighsurfaceareaandporous
structure, andHSAforitsspecificity,biocompatibility,andbiodegradability.
The platinum-basedcompoundsstudiedincludecisplatin(CPT),monoand
diaquo-derivatives(WCPTandW2CPT),andphenanthriplatin(PPT),which
wereexploredfortheirinteractiondynamicswithgraphenesurfacesandHSA.
MD simulationsrevealthatplatinum-basedcomplexesspontaneouslyadsorb
ontothegraphenesurface.Thisadsorptionprocessisprimarilydrivenbyen-
thalpic contributions,suggestingstronginteractionsbetweenthecomplexesand
the graphene.Whilegraphenedemonstratessignificantpotentialforhighdrug
loading, itslackofspecificityininteractionslimitsitseffectivenessintargeted
drug delivery.
In contrast,HSAoffersamoresophisticatedmechanismfordrugdelivery,as
it caninteractspecificallywithdrugmoleculesthroughnon-covalentbinding,
including π-π stackingandhydrogenbonding.Additionally,HSAfunctions
as adrugreservoirthroughreversiblecovalentbinding,significantlyenhancing
drug biodistributionandbioavailability.Thesimulationsinvestigatedthenon-
covalentbindingofphenanthriplatin(PPT),revealingahighaffinityforsite
IIIBonhumanserumalbumin(HSA).Incontrast,cisplatin(CPT)interacts
exclusivelythroughcovalentbinding,primarilywithtwokeyresidues:HIS105
and MET329.Thiscovalentbindingmechanisminvolvesthelossofchloride
ions byCPTuponitsinteractionwithHSA.However,thespecificanticancer
mechanismoftheHSA–CPTcomplexatthecellularlevelremainspoorlyun-
derstood.
Additionally,weexploredthecovalentcomplexesPPT-HSA,focusingonthe
same aminoacidresidues.Ourfindingshighlighttheimportanceofbothco-
valentandnon-covalentinteractionsinimprovingdrugdeliveryeffectiveness.
Understanding theseinteractionscanhelpusdesignbetterdrugdeliverysys-
tems, ultimatelyleadingtobettertherapeuticoutcomes
Sustainability from the start: biochar-based conductive inks enable the streamlined fabrication of green electroanalytical devices
No full textThe design of low-cost and disposable printed electrodes (PEs) has garnered significant attention from the scientific community in recent years. It is crucial to achieve industrial scalability by addressing the cost of conductive inks and ensuring their environmentally friendly disposal. The utilization of biochar, a carbon-rich material derived from the pyrolysis of biomass waste, represents a promising and sustainable alternative to conventional carbon sources. In this study, peanut shell biochar produced with a low-cost pyrolytic kiln reactor was incorporated into conductive inks. As far as we know, biochar-based ink was used to fully fabricate stencil-printed electrodes for the first time. Three different chemical treatments were employed to activate the biochar and enhance its properties. XPS analysis and electrochemical characterization studies showed that organic solvents improved the characteristics of the biochar when compared to acid or alkaline activation treatments. As a proof of concept, the electrodes were used to detect paracetamol as a model analyte for emerging environmental contaminants. An analytical greenness metric (AGREE) was used to infer how environmentally friendly the analytical procedure is, yielding an overall score of 0.72, which indicates a high degree of environmental sustainability. This study underscores the importance of implementing simple strategies to obtain cost-effective PE, thereby promoting green analytical methods using recycled materials such as bio-waste-derived biochar. This approach may reduce dependence on non-environmentally friendly materials for sensor fabrication and contribute to addressing industrial waste recycling challenges
Suppression of Spry1 reduces HIF1 alpha-dependent glycolysis and impairs angiogenesis in BRAF-mutant cutaneous melanoma
Get PDFBackground: About 50% of cutaneous melanoma (CM) harbors the activating BRAFV600 mutation which exerts most of the oncogenic effects through the MAPK signaling pathway. In the last years, a number of MAPK modulators have been identified, including Spry1. In this context, we have recently demonstrated that knockout of Spry1 (Spry1KO) in BRAFV600-mutant CM led to cell cycle arrest and apoptosis, repressed cell proliferation in vitro, and reduced tumor growth in vivo. Despite these findings, however, the precise molecular mechanism linking Spry1 to BRAFV600-mutant CM remains to be elucidated.
Materials and methods: Immunoprecipitation coupled to mass spectrometry was employed to gain insight into Spry1 interactome. Spry1 gene was knocked-out using the CRISPR strategy in the BRAF-mutant cell lines. Transmission electron microscopy was used to assess the relationship between Spry1 expression and mitochondrial
morphology. By using in vitro and in vivo models, the effects of Spry1KO were investigated through RNA-sequencing, quantitative real-time PCR, Western blot, and immunofluorescence analyses. The Seahorse XF24 assay allowed realtime measurement of cellular metabolism in our model. Angiogenic potential was assessed through in vitro tube formation assays and in vivo CD31 staining.
Results: Spry1 was mainly located in mitochondria in BRAFV600-mutant CM cells where it interacted with key molecules involved in mitochondrial homeostasis. Spry1 loss resulted in mitochondrial shape alterations and dysfunction, which associated with increased reactive oxygen species production. In agreement, we found that nuclear hypoxia-inducible factor-1 alpha (HIF1α) protein levels were reduced in Spry1KO clones both in vitro and in vivo along with the expression of its glycolysis related genes. Accordingly, Ingenuity Pathway Analysis identified “HIF1α
Signaling” as the most significant molecular and cellular function affected by Spry1 silencing, whereas the glycolytic function was significantly impaired in Spry1 depleted BRAFV600-mutant CM cells. In addition, our results indicated that the expression of the vascular endothelial growth factor A was down-regulated following Spry1KO, possibly as a result of mitochondrial dysfunction. Consistently, we observed a substantial impairment of angiogenesis, as assessed by the tube formation assay in vitro and the immunofluorescence staining of CD31 in vivo.
Conclusions: Altogether, these findings identify Spry1 as a potential regulator of mitochondrial homeostasis, and uncover a previously unrecognized role for Spry1 in regulating nuclear HIF1α expression and angiogenesis in BRAFV600-mutant CM.
Significance: Spry1KO profoundly impacts on mitochondria homeostasis, while concomitantly impairing HIF1α-dependent glycolysis and reducing angiogenesis in in BRAF-mutant CM cells, thus providing a potential therapeutic target to improve BRAFV600-mutant CM treatment
Management of Eyelid Pathologies That Cause Corneal Lesions
No full textCorneal injuries, which make up 3% of emergency room visits, can vary from small scratches to exposure or trauma-related damage that might be fatal to vision. Mechanical trauma, diseases of the eyelids, neurotrophic abnormalities, and chemical burns are common causes. A thorough examination is necessary for an accurate diagnosis and treatment plan. The goal of this study is to review corneal damage from both functional and traumatic causes associated with eyelid problems and surgical therapy. Based on a comprehensive analysis of the literature, it focuses on identifying important eyelid diseases that can compromise the integrity of the corneal epithelium, including entropion, ectropion, trichiasis, distichiasis, epiblepharon, and lagophthalmos. To find research on surgical care of eyelid disorders resulting in corneal injury, the MEDLINE and Reference Citation Analysis databases were searched (from 2008 to the present). At least two impartial reviewers examined every article to guarantee that all pertinent articles were found. Relevant publications were found using a literature search. Each pertinent paper's reference list was manually checked to include relevant documents the original search missed. There were 28 papers about surgical management of eyelid abnormalities that could jeopardize the integrity of the corneal epithelium: entropion, ectropion, trichiasis, distichiasis, epiblepharon, and lagophthalmos. Entropion treatment was the subject of the majority of these studies. The review strongly emphasizes determining the precise anatomical source of corneal injury in disorders of the eyelids and customizing surgical techniques accordingly. Cooperation between plastic surgeons and ophthalmologists is crucial to manage complicated situations and guarantee stable, long-term results
Anomaly Detection with Machine Learning on Time Series: Unveiling Lost Transients Data
No full textMany modern scientific fields deal with phenomena so complex that the resulting data cannot be accurately described using most statistical techniques. In some fields, such as Astrophysics and Multi-Messenger Astronomy, Machine Learning has offered many tools to help researchers, with techniques capable of understanding the dependencies of many phenomena with the underlying physical models. A common problem is the detection of anomalies in multivariate time series where the data have dependencies with the physics that characterizes the context. We present here a tool to understand the expected evolution of time series in order to discriminate and identify transient events from the normal behavior of a series of data evolving in time. The software employs Machine Learning techniques and was developed upon the use case of identifying high-energy transients, such as Gamma-Ray Bursts, in the data from the Fermi Gammaray Space Telescope, using its background rejection system, the Anti-Coincidence Detector. The latter has not been previously used for scientific purposes, so it offers a fertile ground for the development of this software. In this paper, we introduce our framework starting with the concept of time series, specifically the count rates of particles in the Anti-Coincidence Detector, and the orbit configuration of the Fermi satellite. The software implements Machine Learning models such as Feed-Forward Neural Network and Recurrent Neural Network, employed to learn the orbital Fermi configuration to predict the background. We then implemented a triggering algorithm called FOCuS, which identifies significant deviations from the background, signaling the presence of anomalies and, perhaps, astrophysical transients in the dataset. This tool can be adapted for various signals, making it applicable across different contexts and research
I dialetti sloveni del Friuli: una riflessione sulla loro vitalità alla luce dei parametri UNESCO
No full textImpact of ELN clinical signs and symptoms on the thrombotic risk in polycythemia vera patients treated with front-line hydroxyurea
Get PDFThe European LeukemiaNet recently proposed specific Clinical Signs and Symptoms (CSSs) that may trigger cytoreduction in patients with polycythemia vera (PV) at low thrombotic risk (LR). To evaluate the impact of CSSs on the thrombotic risk of patients at LR, high risk by age only (HR-AGE) or by previous thrombosis (HR-THRO), we conducted a multicenter cooperative study (NCT06134102) involving 739 PV patients treated with first-line hydroxyurea. At hydroxyurea start, 443 patients had at least one CSS. In patients with and without CSSs, the incidence rate ratio of thrombosis was 2.2 and 0.7 per 100 patient-years, respectively (p < 0.001), and the thrombosis-free survival (TFS) adjusted for delayed entry at 5 years was 88.7% and 96.1% (p < 0.001). The best 5-years TFS was observed in LR and HR-AGE with no CSSs (LR, 100%; HR-AGE: 98.1%). LR, HR-AGE patients with CSSs and HR-THRO patients without CSSs had comparable TFS (89.2%, 92.1% and 88.8%, respectively). TFS of HR-THRO patients was 80.2%. In multivariate analysis including each CSS, inadequate hematocrit control (HR: 2.32, p < 0.001), relevant CVRFs (HR: 2.87, p = 0.006), progressive splenomegaly (HR: 4.02, p = 0.03) and previous thrombosis (HR: 3.76, p < 0.001) remained significantly associated with thrombotic risk. CSSs identify an increased thrombotic risk phenotype across all risk categories. (Figure presented.