University of Udine
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Should pathologists and clinicians continue to consider Grade Group 1 (Gleason score ≤6) prostate cancer as a true carcinoma? Let's hear from patient advocates
No full textTo the Editor, The current grading system for prostate cancer (PCA) includes 5 Grade Groups (GG): GG1 (Gleason score ≤ 6); GG2 (Gleason score 3+4); GG3 (Gleason score 4+3); GG4 (Gleason score 4+4; or 3+5; or 5+3); GG5 (Gleason scores 4+5/5+4/5+5). The GG system is one of the most important predictors of outcome in PCA patients..
Stress concentration optimization for functionally graded plates with noncircular holes
Get PDFIn this paper, the minimization of the stress concentration due to noncircular holes and cutouts in functionally graded infinite plates subjected to uni-axial traction is considered. Under reasonable assumptions regarding the type of material variation, an optimization problem aimed at determining the best Young's modulus distribution throughout the plate without prefixing its functional form is numerically solved. The solution technique involves embedding the isoparametric finite element method within a sequential quadratic programming algorithm for constrained nonlinear programming problems. Motivated by results of a recent study concerning infinite plates with a circular hole, this work presents a non-trivial generalization of the best tailoring approach for a broader class of geometrical discontinuities. Three practical examples such as elliptic holes, rectangular slots with semicircular ends and circular holes with opposite semicircular lobes are considered and numerical optimal solutions for the Young's modulus distribution lead to elastic performance that outperforms the homogeneous and commonly employed prefixed gradation laws. The associated stress behavior is shown in graphical form for different stiffness ratios of the constituents, discussed and compared to the homogeneous plates
Longevity Comparison by Gender: Exploring the Future Through an Evidence-Based Approach
No full textOur demographic study provides a detailed picture of the short-term, weekly, mortality fluctuations charactering females and males over more than a decade. We follow an evidence-based approach, since we use data from the Human Mortality Database to detect stylized empirical evidence about the behaviour of mortality, during normal times and in the most recent time span, highly affected by the COVID-19 pandemic disease. Our study relies on time-series mortality data collected at a finer scale than traditionally done in the actuarial literature and encompasses different age groups and gender. The empirical evidence represents the starting point for exploring the future mortality patterns. Our quantitative analysis, namely based on stochastic mortality modelling, indeed, answers the question whether accounting for higher frequency mortality data delivers more reliable mortality projections, namely projections that approximate more closely the realized mortality phenomenon
Know your enemy: investigations on Varroa destructor – A step forward in understanding its biology and promoting in vitro rearing
Get PDFThis PhD thesis offers a comprehensive investigation of the rearing challenges associated with Varroa destructor, the major ectoparasite affecting honey bee colonies worldwide. The introduction chapter details the mite’s biology, morphology, and life cycle, emphasizing its significant detrimental impact on bee health. The reasons for rearing Varroa mites are explained in the same chapter, and the issues regarding the rearing of arthropods ectoparasite are deeply analysed. The key concept of the introduction is the definition of the life history of an organism, which is composed of factors affecting survival and factors affecting reproduction. These factors are the ones that need to be studied in order to replicate the life history of the mite in a laboratory environment.
Chapter 2 presents a thorough literature review and state-of-the-art analysis of past research efforts, spanning studies from the 1970s to the present. These studies examined various methods of maintaining and rearing Varroa mites in vitro. The document highlights the complexity of replicating the hive environment, where factors such as temperature, humidity, feeding cues, and host characteristics are crucial for mite survival and reproduction. From this review it was possible to identify which questions, regarding Varroa biology, were still open and could be answered by the present research.
From chapter 3 to 10 the experimental work is reported. The research efforts were focused on the following aspects.
Optimal host and parasite condition: determining which developmental stage of the host best supports mite longevity (chapter 3) and investigating the influence of mite age and reproductive history on mite’ survival (chapter 4) under artificial conditions.
Artificial Feeding System: evaluating whether completely artificial diets can meet the nutritional needs of Varroa mites (chapter 5) and if the physical configuration of rearing chambers (chapter 6) affects mites’ survival; moreover the efficacy of different plastic membranes (chapter 7) in the artificial feeding of Varroa was determined.
Mite Physiology: investigating the role of the phoretic phase on mite reproduction (chapter 8) and the reproduction of the mite in the absence of the living host (chapter 9).
Host Resistance: exploring preliminary evidence that resistant bee strains might reduce Varroa fertility (chapter 10).
The general conclusions are presented in chapter 11, followed by the references cited in this thesis. The appendix includes other scientific works produced during the PhD program
Small molecule inhibitors of hnRNPA2B1–RNA interactions reveal a predictable sorting of RNA subsets into extracellular vesicles
Get PDFExtracellular vesicles (EVs) are cell-secreted membranous particles contributing to intercellular communication. Coding and noncoding RNAs can be detected as EV cargo, and RNA-binding proteins (RBPs), such as hnRNPA2B1, have been circumstantially implicated in EV-RNA sorting mechanisms. However, the contribution of competitive RBP–RNA interactions responsible for RNA-sorting outcomes is still unclear, especially for predicting the EV-RNA content. We designed a reverse proteomic analysis exploiting the EV-RNA to identify intracellular protein binders in vitro. Using cells expressing a recombinant hnRNPA2B1 to normalize competitive interactions, we prioritized a network of heterogeneous nuclear ribonucleoproteins and purine-rich RNA sequences subsequently validated in secreted EV-RNA through short fluorescent RNA oligos. Then, we designed a GGGAG-enriched RNA probe that efficiently interacted with a full-length human hnRNPA2B1 protein. We exploited the interaction to conduct a pharmacological screening and identify inhibitors of the protein–RNA binding. Small molecules were orthogonally validated through biochemical and cell-based approaches. Selected drugs remarkably impacted secreted EV-RNAs and reduced an RNA-dependent, EV-mediated paracrine activation of NF-kB in recipient cells. These results demonstrate the relevance of post-transcriptional mechanisms for EV-RNA sorting and the possibility of predicting the EV-RNA quality for developing innovative strategies targeting discrete paracrine functions
Enhancing valuation of variable annuities in Lévy models with stochastic interest rate
No full textThis paper extends the valuation and optimal surrender framework for variable annuities with guaranteed minimum benefits in a Lévy equity market environment by incorporating a stochastic interest rate described by the Hull-White model. This approach frames a more dynamic and realistic financial setting compared to previous literature. We exploit a robust valuation mechanism employing a hybrid numerical method that merges tree methods for interest rate modeling with finite difference techniques for the underlying asset price. This method is particularly effective for addressing the complexities of variable annuities, where periodic fees and mortality risks are significant factors. Our findings reveal the influence of stochastic interest rates on the strategic decision-making process concerning the surrender of these financial instruments. Through comprehensive numerical experiments, and by comparing our results with those obtained through the Longstaff-Schwartz Monte Carlo method, we illustrate how our refined model can guide insurers in designing contracts that equitably balance the interests of both parties. This is particularly relevant in discouraging premature surrenders while adapting to the realistic fluctuations of financial markets. Lastly, a comparative statics analysis with varying interest rate parameters underscores the impact of interest rates on the cost of the optimal surrender strategy, emphasizing the importance of accurately modeling stochastic interest rates
APE1 condensation in nucleoli of non-cancer cells depends on rRNA transcription and forming G-quadruplex RNA structures
Get PDFAPE1 [apurinic/apyrimidinic (AP) endodeoxyribonuclease 1] is the main endonuclease of the base excision repair pathway acting on abasic (AP) sites in DNA. APE1 is an abundant nuclear protein, and improper expression or localization of this factor could lead to the accumulation of toxic DNA intermediates. Altered APE1 subcellular distribution and expression are associated with cancer development, suggesting the importance of a fine-tuning mechanism for APE1 activities. Recent works highlighted the presence of APE1 within nucleoli of cancer cells and the ability of APE1 to form biomolecular condensate. However, whether secondary structures of ribosomal RNA (rRNA) influence the nucleolar localization of APE1 remains poorly understood. Since protein overexpression can result in artificial nucleolar accumulation, it is imperative to have appropriate cellular models to study APE1 trafficking under physiological conditions. To address this issue, we generated a murine embryonic stem cell line expressing endogenous fluorescent-tagged APE1. Live-cell imaging demonstrates that APE1 nucleolar accumulation requires active rRNA transcription and is modulated by different genotoxicants. In vitro experiments showed that APE1 condensate formation depends on RNA-forming G-quadruplex structures and relies on critical lysine residues. This study sheds light on the mechanisms underlying APE1 trafficking to the nucleolus and the formation of RNA-dependent APE1 nucleolar condensates
The Boss Is Back in Town: Insights into the Wolf Recolonization of a Highly Anthropized and Low-Ungulate-Density Environment
Get PDFThis study documents the recolonization of the wolf using opportunistic and systematic data, including camera trapping and scat surveys in south-eastern Italy. Wolf distribution was mapped using a 10 × 10 km grid, and Generalized Linear Models (GLMs) were applied to identify environmental and anthropogenic drivers of stable presence. Camera trapping and scat analyses were used to provide the first insights into the activity patterns and feeding habits of the species. The results showed a significant expansion in wolf range, with occurrence increasing by 120%, especially in areas with high forest cover. During 1402 camera-trap nights, wolves and wild prey species displayed primarily nocturnal activity, reducing overlap with human presence, though prey activity peaks were offset from those of wolves. Diet analysis of 75 scats revealed a high occurrence of livestock and pets, along with all wild species living in the area (i.e., ungulates, medium-sized and micromammals). These findings underscore the wolf’s ecological adaptability and ability to thrive in heavily altered landscapes. Indeed, this study shows how wolves were able to occupy even suboptimal areas, taking advantage of both anthropogenic and wild trophic resources, still displaying nocturnal activity to lower the probability of encounters with humans
Bridging the Gap: Genetic Insights into Graft Compatibility for Enhanced Kiwifruit Production
Get PDFKiwifruit, with its unique flavor, nutritional value, and economic benefits, has gained significant attention in agriculture production. Kiwifruit plants have traditionally been propagated without grafting, but recently, grafting has become a more common practice. A new and complex disease called Kiwifruit Vine Decline Syndrome (KVDS) has emerged in different kiwifruit-growing areas. The syndrome was first recognized in Italy, although similar symptoms had been observed in New Zealand during the 1990s before subsequently spreading worldwide. While kiwifruit was not initially grafted in commercial orchards, the expansion of cultivation into regions with heavy soils or other challenging environmental conditions may make grafting selected kiwifruit cultivars onto KVDS-resistant or -tolerant rootstocks essential for the future of this crop. Grafting is a common horticultural practice, widely used to propagate several commercially important fruit crops, including kiwifruits, apples, grapes, citrus, peaches, apricots, and vegetables. Grafting methods and genetic compatibility have a crucial impact on fruit quality, yield, environmental adaptability, and disease resistance. Achieving successful compatibility involves a series of steps. During grafting, some scion/rootstock combinations exhibit poor graft compatibility, preventing the formation of a successful graft union. Identifying symptoms of graft incompatibility can be challenging, as they are not always evident in the first year after grafting. The causes of graft incompatibility are still largely unknown, especially in the case of kiwifruit. This review aims to examine the mechanisms of graft compatibility and incompatibility across different fruit crops. This review’s goal is to identify potential markers and techniques that could enhance grafting success and boost the commercial production of kiwifruit
Efficient, secure and green future scenarios: An application of foresight methodologies on seaports digitalisation
Get PDFThe relentless progression of digitalisation permeates every sector, including maritime and transport industries. This study explores the digitalisation landscape expected to evolve over the next decade, with a particular focus on its impact on ports. Employing a combination of Delphi and Roadmapping analyses, it seeks to identify the most probable, impactful, and desirable scenarios. The findings give insight on two principal aspects: they identify the digitalisation trends most related and impactful to future ports, and they provide guidance on which technologies to prioritise, also providing their phased implementation to achieve specific scenarios over time. The research is structured around three alternative scenarios: efficiency-driven, security-oriented, and green-centric, each with distinct implications for port development and management