University of Udine
  • Udine, UD, Italy
Recent publications
In the framework of the rational design of macromolecules capable of binding to a specific target for biosensing applications, we here further develop an evolutionary protocol designed to optimize the binding affinity of protein binders. In particular we focus on the optimization of the binding portion of small antibody fragments known as nanobodies (or VHH) and choose the hen egg white lysozyme (HEWL) as our target. By implementing a replica exchange scheme for this optimization, we show that an initial hit is not needed and similar solutions can be found by either optimizing an already known anti-HEWL VHH or a randomly selected binder (here a VHH selective towards another macromolecule). While we believe that exhaustive searches of the mutation space are most appropriate when only few key residues have to be optimized, in case a lead binder is not available the proposed evolutionary algorithm should be instead the method of choice.
This paper is concerned with the estimation of the mass density in a rectangular taut membrane from finite eigenvalue data of the small undamped transverse vibration. It is known that the first lower eigenvalues of the membrane supported at the boundary may allow the reconstruction of small perturbations of the uniform density, provided that the mass density is symmetric with respect to both the midlines of the domain. Here we show how the addition of suitable sets of eigenvalues corresponding to different boundary conditions can be useful for the determination of mass densities either with one symmetry axis only or without symmetry. The reconstruction procedure is based on a sequence of linearizations of the inverse problem in a neighborhood of the uniform membrane, under the assumption that the eigenvalues of the initial membrane used in identification are all simple. An extended series of numerical simulations performed for various mass densities allowed to test the effectiveness of the reconstruction, and also to highlight some indeterminacy inherent in this inverse eigenvalue problem with finite data.
This paper presents a simulation and experimental study on a passive “click” mechanism, which is designed to adapt the angle of incidence of a racing car flap along a circuit to have high down force when the car undertakes low speed corners and low drag force when the car sprints along the straights. The mechanism is composed by four rigid linkages connected via flexible pivot junctions. The paper first provides a parametric study that shows how the stiffness of the flexible pivot junctions, the length of the linkages and the rest angles of the linkages influence the typical N-shaped resistant moment–joint rotation function, which is at the basis of the clicking effect. The parametric study is then used to design a mechanism, which is characterised by a stable high pitch equilibrium configuration only and maintains the N-shaped moment-rotation feature such that the flap snaps from high-to-low pitch and vice versa at given critical speeds during acceleration and deceleration of the car. Finally, the dynamic response of a flap mounted on the proposed monostable clicking joint is analysed in detail and contrasted with that of a flap fixed on classical passive joints built with a stiff spring or a soft pre-loaded spring.
Triple-negative (TN) metastatic breast cancer (mBC) represents the most challenging scenario withing mBC framework, and it has been only slightly affected by the tremendous advancements in terms of drug availability and survival prolongation we have witnessed in the last years for advanced disease. However, although chemotherapy still represents the mainstay of TN mBC management, in the past years, several novel effective agents have been developed and made available in the clinical practice setting. Within this framework, a panel composed of a scientific board of 17 internationally recognized breast oncologists and 42 oncologists working within local spoke centers, addressed 26 high-priority statements, including grey areas, regarding the management of TN mBC. A structured methodology based on a modified Delphi approach to administer the survey and the Nominal Group Technique to capture perceptions and preferences on the management of TN mBC within the Italian Oncology community were adopted. The Panel produced a set of prioritized considerations/consensus statements reflecting the Panel position on diagnostic and staging approach, first-line and second-line treatments of PD-L1-positive/germline BRCA (gBRCA) wild-type, PD-L1-positive/gBRCA mutated, PD-L1-negative/gBRCA wild-type and PD-L1-negative/gBRCA mutated TN mBC. The Panel critically and comprehensively discussed the most relevant and/or unexpected results and put forward possible interpretations for statements not reaching the consensus threshold.
A new LC-MS/MS method for the quantification of lenvatinib (LENVA) in venous Dried Blood Spot (DBS) samples has been presented. This method is characterized by a short run time (4 min), requires a volumetric sampling of 10 µL and extraction of the entire spot to avoid hematocrit (Hct) and spot volume effects. The quantification method was successfully validated in the range of 5.00-2000 ng/mL on two different DBS filter papers (Whatman 31 ET CHR and Whatman 903) according to European Medicines Agency (EMA) and Food and Drug Administration (FDA) guidelines, European Bioanalysis Forum (EBF), and International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT) recommendations. During the validation process, the following parameters were evaluated: recovery (≥ 77% for both filter papers), absence of matrix effect, process efficiency (close to 72% for Whatman 31 ET CHR and close to 77% for Whatman 903), Hct effect (CV ≤ 6.3% and accuracy within 96-112%), linearity (r ≥ 0.998 for Whatman 31 ET CHR and r ≥ 0.999 for Whatman 903), intra- and inter-day precision (CV ≤ 8.8%) and accuracy (92.8-108%), selectivity and sensitivity, reproducibility with incurred samples reanalysis (ISR), and stability. This method was applied to quantify venous DBS samples from patients with hepatocellular carcinoma treated with LENVA enrolled in a cross-validation study (CRO-2018-83). A good correlation between LENVA plasma concentration determined by standard procedure and the new developed DBS LENVA method (R2 ≥ 0.996) has been observed.
Psychological distance is “a subjective experience that something is close or far away from the self, here, and now” (Trope & Liberman 2010, p. 440). This research investigates heritage tourism from the perspective of Construal Level theory, which postulates that individuals mentally represent objects and events by adopting either low or high construal levels. We show that heritage tourism leads tourists to adopt a higher psychological distance and therefore a higher construal level. In turn, this higher construal negatively affects destination loyalty and perceived uniqueness. However, authenticity and engagement moderate the heritage–construal relationship, counterbalancing the higher psychological distance induced by heritage. We explore these relationships in two studies focusing on contemporary heritage sites. This further allows to compare visitors’ mental representations of the experience, based on their memory type. The paper concludes by addressing implications for theory and practice.
We prove a necessary and sufficient condition for the existence of a T-periodic solution for the time-periodic second order differential equation x¨+f(t,x)+p(t,x,x˙)=0, where f grows superlinearly in x uniformly in time, while p is bounded. Our method is based on a fixed-point theorem which uses the rotational properties of the dynamics.
We study almost Dedekind domains with respect to the failure of ideals to have radical factorization, that is, we study how to measure how far an almost Dedekind domain is from being an SP-domain. To do so, we consider the maximal space ℳ = Max ⁡ ( R ) {\mathcal{M}=\operatorname{Max}(R)} of an almost Dedekind domain R , interpreting its (fractional) ideals as maps from ℳ {\mathcal{M}} to ℤ {\mathbb{Z}} , and looking at the continuity of these maps when ℳ {\mathcal{M}} is endowed with the inverse topology and ℤ {\mathbb{Z}} with the discrete topology. We generalize the concept of critical ideals by introducing a well-ordered chain of closed subsets of ℳ {\mathcal{M}} (of which the set of critical ideals is the first step) and use it to define the class of SP-scattered domains , which includes the almost Dedekind domains such that ℳ {\mathcal{M}} is scattered and, in particular, the almost Dedekind domains such that ℳ {\mathcal{M}} is countable. We show that for this class of rings the group Inv ⁢ ( R ) {\mathrm{Inv}(R)} is free by expressing it as a direct sum of groups of continuous maps, and that, for every length function ℓ {\ell} on R and every ideal I of R , the length of R / I {R/I} is equal to the length of R / rad ⁡ ( I ) {R/{\operatorname{rad}(I)}} .
Added Damping and Stiffness (ADAS) steel dissipators are among the most classical devices installed in dissipative bracing systems for the advanced seismic retrofit of frame buildings. An energy-based sizing procedure is formulated in this study for this class of dampers, where the total number of constituting plates is directly related, without iterative steps, to the supplementary damping energy required to jointly reduce stress states in structural members and storey drifts. The stiffening effects of the dissipative braces are expressly controlled, so as to compensate for the increase in storey shears induced by their incorporation in the frame skeleton. The sizing procedure is demonstratively applied to the retrofit design of a 6-storey reinforced concrete building, to explicate and discuss the use of its analytical relations and relevant limitations in practice. The evaluation of the seismic performance of the structure in retrofitted conditions allows comparing the response of the dissipative bracing system with the hypotheses formulated at the sizing stage.
The fifth-edition of World Health Organization (WHO) Classification of Tumors series for urinary and male genital tract tumors has been published, six years later the fourth-edition. In these years, new treatment approaches have been implemented and new molecular data on urological cancers are known. Morphology remains the groundwork for taxonomy of the urinary tract tumors. However, a molecular approach to classification of urothelial carcinomas and the management of selected neoplasms with new therapeutic modalities such as immunotherapy are emerging. More data are needed for the application of these advances in routine pathology practice and patient management. The 2022 World Health Organization (WHO) Classification of Tumors of the Urinary System and Male Genital Organs represents an update in classification on urinary tract tumors. It also offers new insights with regards to the grading of heterogeneous non-invasive urothelial neoplasms, the definition of inverted neoplasms, the grading of invasive urothelial carcinomas, the diversity of morphological appearance of urothelial carcinomas, the definition of precursor lesions and the lineage of differentiation of the tumors.
Controlling access to genomic information and maintaining its stability are key aspects of cell life. Histone acetylation is a reversible epigenetic modification that allows access to DNA and the assembly of protein complexes that regulate mainly transcription but also other activities. Enzymes known as histone deacetylases (HDACs) are involved in the removal of the acetyl-group or in some cases of small hydrophobic moieties from histones but also from the non-histone substrate. The main achievement of HDACs on histones is to repress transcription and promote the formation of more compact chromatin. There are 18 different HDACs encoded in the human genome. Here we will discuss HDAC4, a member of the class IIa family, and its possible contribution to cancer development.
Test equating is a statistical procedure to make scores from different test forms comparable and interchangeable. Focusing on an IRT approach, this paper proposes a novel method that simultaneously links the item parameter estimates of a large number of test forms. Our proposal differentiates itself from the current state of the art by using likelihood-based methods and by taking into account the heteroskedasticity and the correlation of the item parameter estimates of each form. Simulation studies show that our proposal yields equating coefficient estimates which are more efficient than what is currently available in the literature.
High risk multiple myeloma (HRMM) at diagnosis is currently recognized according to the Revised International Staging System (R-ISS) which was set up in 2015. Since then, new clinical and biological prognostic factors have been developed, which could implement the definition of High Risk (HR) category. We conducted a survey in order to identify which additional parameters, both clinical and biological, are considered more useful for the clinical practice and to evaluate if the management of Multiple Myeloma (MM) should change on the basis of the risk category. A questionnaire, consisting of 8 statements, was submitted to 6 Italian experts, from the European Myeloma Network (EMN) Research Italy, using the Delphi method. The colleagues were asked to answer each question using a scale between 0 and 100. If a statement did not reach at least 75 out of 100 points from all the participants, it was rephrased on the basis of the proposal of the experts and resubmitted in a second or further round, until a consensus was reached among all. From the first round of the survey a strong consensus was reached regarding the opportunity to revise the R-ISS including chromosome 1 abnormality, TP53 mutation or deletion, circulating plasma cells by next generation flow and extramedullary plasmacytomas. No consensus was reached for the definition of “double hit” MM and for the application in clinical practice of treatment strategies based on the risk category. In the second round of the Delphi questionnaire, “double-hit” MM was recognized by the association of at least two high-risk cytogenetic or molecular abnormalities. Moreover, the experts agreed to reserve an intensified treatment only to specific conditions, such as plasma cell leukaemia or patients with multiple extramedullary plasmacytomas, while they admitted that there are not sufficient real word data in order to modify treatment on the basis of MRD assessment in clinical practice. This survey suggests that the definition of HRMM should be implemented by additional clinical and biological risk factors, that will be useful to guide treatment in the future.
The identification of damage in the connection of steel-concrete composite beams is pursued by means of Convolutional Neural Networks. The data used for training the networks are gray level images obtained by converting a set of transmissibility functions of the beam. It is shown how simple Convolutional Neural Networks can be trained for the identification of the damage by evaluating its position and intensity. Data availability is thoroughly discussed highlighting the effects of various factors, among them the number and richness of the images used in the training phase, on the predictive capabilities of the network. In this regard, the results obtained are satisfactory as confirmed also by comparisons with data extracted from an experimental campaign. The problem of the unavoidable presence of modelling errors is also discussed and counteracted.
The aim of the present work was to investigate the influence of fasting and refeeding on body condition, gut physiology and microbiota in reared O. mykiss . Ninety-six fish were randomly allotted among three groups subjected to different feeding plan: C (control, fed for 5 weeks); R (restricted ration over 3 weeks followed by 2 weeks feeding); F (fasted over 3 weeks followed by 2 weeks feeding) in a well’s fresh water flow-through rearing plan. Sampling occurred at 0, 1, 2, 4, 7, 14 days during the refeeding period. At day 0 and throughout the feeding period until day 14, the weight of the fish was significantly affected by the feeding restriction. Feed deprivation reduced significantly the viscerosomatic and hepatosomatic indexes. Brush border membrane enzymes’ specific activity was modulated by feeding regimes until day 7, to level in all experimental groups at day 14. At the end of the restricted/fasted period, the microbiota of the C group was made up of 70% of Actinobacteria, 24% of Proteobacteria, 4.2% of Firmicutes and < 1% of Bacteroides, while the restricted and fasted group were characterized by a strong reduction of Actinobacteria, and a significant increase in Bacteroidetes and Firmicutes. The feed deprivation determined a dysbiosis, allowing the development of different commensal or pathogenic bacteria. In conclusion, the effects of 2 weeks of feed deprivation, excluding those related to body weight, are gradually mitigated by refeeding, which allows the restoration of digestive functions and a healthy intestinal microbiota.
During the Assyrian rule over Northern Mesopotamia (present-day northern Iraq), complex systems of canals were built to increase the surface of cultivable land and improve the movement of people and goods across the irrigated waterscape of the hinterland of Nineveh and other major urban centres, with the aim of granting socio-economic prosperity to the empire. Nevertheless, supra-regional political instability eventually led to the rapid downfall of the Assyrian state during the late seventh century BCE, causing the swift abandonment of the canal systems. In this study, we examine the post-abandonment formation processes of the natural and anthropogenic infillings of three portions of King Sennacherib’s Khinis canal system (705–681 BCE, northwestern Kurdistan Region of Iraq) through means of archaeological, sedimentological and micromorphological analyses. We identify water lain sediments, desiccation features, colluvial gravel intake and pastoral occupation layers, anchoring the deposit to radiometric dating and contextualising it against the known regional climatic history. The interpretation of pedostratigraphic evidence highlights subsequent phases of use, abandonment, and repurposing of the canals, reflecting shifts in land-use from agriculture to pastoralism and dynamic adaptation and resilience of the local ancient communities in response to Late-Holocene climate changes and geopolitical events.
Modular Multilevel Converters (MMCs) are becoming more and more popular in medium-voltage applications thanks to several interesting features. The major limitation for applications with variable speed drives (VSDs) is the submodule capacitors’ voltage ripple, which depends directly on the output current/torque and inversely on the output frequency/speed. Among all the hybrid MMC topologies addressed in recent literature, the Flying-Capacitor Passive Cross-Connected arms (FC-PCC) MMC seems one of the most promising to cope with this issue. This article provides a comprehensive overview of its features and capabilities. The main open issues limiting safe and reliable converter operation in VSD applications are addressed, and novel solutions are presented, such as the optimization of the converter digital control strategy, the distributed implementation of the architecture, the L‑C oscillations damping during the pre-charge/start-up of the converter, and the optimized arm inductor design based on magnetic coupling concepts. The effectiveness of all the proposals is demonstrated through an accurate simulation of a 22 kW Permanent Magnet Synchronous Machine (PMSM) drive, including a complete model of the effects of the real-time communication and the processing latency. A prototype of the system has been developed employing some known and novel architectural solutions, as discussed in the last section of the paper.
Early detection of the emergence of a new variant of concern (VoC) is essential to develop strategies that contain epidemic outbreaks. For example, knowing in which region a VoC starts spreading enables prompt actions to circumscribe the geographical area where the new variant can spread, by containing it locally. This paper presents ‘funnel plots’ as a statistical process control method that, unlike tools whose purpose is to identify rises of the reproduction number (Rt), detects when a regional Rt departs from the national average and thus represents an anomaly. The name of the method refers to the funnel-like shape of the scatter plot that the data take on. Control limits with prescribed false alarm rate are derived from the observation that regional Rt's are normally distributed with variance inversely proportional to the number of infectious cases. The method is validated on public COVID-19 data demonstrating its efficacy in the early detection of SARS-CoV-2 variants in India, South Africa, England, and Italy, as well as of a malfunctioning episode of the diagnostic infrastructure in England, during which the Immensa lab in Wolverhampton gave 43,000 incorrect negative tests relative to South West and West Midlands territories.
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4,105 members
Roberto Carniel
  • Polytechnic Department of Engineering and Architecture
Nicola Tomasi
  • Department of Agricultural and Environmental Sciences
carlo alberto Beltrami
  • Department of Medical and Biological Sciences
Angelo Gaudio
  • Department of Humanities and Culturale Heritage
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