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Efficacy of 4% 5-Fluorouracil Cream in the Treatment of Actinic Keratoses: A Single-Center Experience.
No full textBackground/Objectives: Actinic keratoses (AKs), also known as solar keratoses, are considered premalignant skin lesions that can evolve into squamous cell carcinoma (SCC). Among the available options, 5-fluorouracil (5-FU) remains a cornerstone. Methods: This study is a retrospective analysis of our database of the non-melanoma skin cancer outpatient clinic. The main objective was to evaluate patients treated with 4% 5-FU cream for AK lesions. The efficacy of 4% 5-FU was evaluated retrospectively by measuring the percentage of patients who achieved complete clearance. A secondary efficacy measure was the percentage of partial clearance, defined as at least a 75% reduction in lesion count. Additionally, the study aimed to assess the safety of 4% 5-FU cream. Results: We included 150 patients clinically diagnosed with AK, treated with 4% 5-FU cream and evaluated 432 lesions. Complete clearance of lesions was observed in 138 patients (92%) with partial clearance in 12 patients (8%). At 12 months, the recurrence rate was 11%. Conclusions: Based on our analysis, 4% 5-FU cream is an effective and well-tolerated treatment for AKs, particularly in patients with extensive field cancerization. While local skin reactions are a natural part of its mechanism, they are manageable and do not outweigh clinical benefits
Role of Kcash2 and Hedgehog signaling pathway in Inflammatory Bowel Disease-associated to Colorectal Cancer
No full textThe Hedgehog (Hh) pathway regulates intestinal stem cell renewal and differentiation, and
its dysregulation contributes to several cancers, including inflammatory bowel disease
(IBD)-related colorectal cancer (CRC). Among its inhibitors, KCASH2 acts as a tumor
suppressor by promoting HDAC1 degradation, maintaining Gli1 acetylation, and repressing
Hh signaling.
In silico analyses of ulcerative colitis-associated CRC patients revealed reduced KCASH2
expression and an inverse correlation with Gli1, suggesting a role for KCASH2 in disease
progression. Using a KCASH2-KO mouse model combined with AOM/DSS treatment, we
demonstrate that KCASH2 loss increases susceptibility to DSS-induced injury, as evidenced
by higher mortality, severe weight loss, colon shortening, impaired epithelial recovery and
diffuse immune cells infiltration. Consistently, KCASH2 deficiency was associated with
enhanced NF-κB activation, impaired apoptotic clearance of damaged cells, and
downregulation of epithelial and tight junction markers. In vitro, KCASH2-silenced HT29
cells showed delayed wound closure under both basal and inflammatory conditions,
confirming its role in epithelial regeneration.
At tumorigenic stages, KCASH2-KO mice developed more numerous, larger and highergrade
dysplastic lesions than WT. Molecular analyses revealed Hh pathway
hyperactivation, together with aberrant Wnt/β-catenin and Notch signaling and reduced
ERK phosphorylation, indicating oncogenic network reprogramming. In conclusion,
KCASH2 loss exacerbates inflammation, impairs epithelial repair, and promotes oncogenic
signaling crosstalk, thereby accelerating IBD-related CRC. These findings identify KCASH2
as a key regulator of colonic homeostasis and a potential therapeutic target for inflammationdriven
tumorigenesis
Radiative cooling in hybrid polymeric films: from design optimization to quantitative performance evaluation
No full textPassive daytime radiative cooling (PDRC) reduces heat load by reflecting solar radiation while emitting thermal energy through the atmospheric window. This thesis investigates polymer- based strategies that couple intrinsic vibrational emissivity with optical design to deliver scalable, flexible cooling films. First, free-standing styrenic block copolymers—SIS, SBS, and SEBS—were fabricated by solution casting and characterized via FTIR and UV–Vis–NIR spectroscopy to relate backbone chemistry to spectral response across 0.4–25 μm. Angular and polarization studies showed minimal spectral variation, indicating isotropic radiative behavior suitable for real-world orientations. Building on this baseline, an SBS platform was combined with surface-modified TiO2 to enhance solar back-scattering while preserving mid-IR emissivity, with processing routes optimized for uniform dispersion and free-standing films. Finally, molecular emissivity tuning was explored by doping PMMA with zinc-phthalocyanine derivatives at controlled concentrations, strengthening vibrational bands within the 3–5 μm and 8–13 μm windows while maintaining visible transparency. Across these systems, a unified, dimensionless figure of merit was introduced to couple solar-weighted absorbance with mid- IR emissivity, enabling fair comparison independent of weather or test setups. The results establish structure–property relationships: unsaturated styrenics intrinsically favor emission, scattering additives raise solar reflectance when compatibilized, and organic chromophores offer a tunable route to 24-hour thermal management. The materials are free-standing, solution- processed, and mechanically compliant, supporting large-area manufacturing and deposition on non-planar substrates. Overall, this work advances a multiscale design framework—from polymer chemistry to optical engineering and molecular doping—for passive radiative cooling coatings and films, and outlines guidelines for standardized spectral evaluation without relying on site-specific temperature measurements
Assessing Ship Emissions: An Estimation Approach Applied to the Port of Catania (Italy)
No full textIn recent years, reducing emissions from maritime transport has become a priority for many port cities. Indeed, ships are a significant source of pollutants such as carbon dioxide (CO2), nitrogen oxides (NOx), sulphur dioxide (SO2), particulate matter (PM) and other pollutants that contribute to air pollution and climate change. The problem is particularly relevant in ports, where ships spend long periods at berth with their engines running to keep on-board systems running, an operational phase known as hoteling. To address this problem, there are different methods of monitoring ship emissions. One approach is direct monitoring, which involves the use of sensors that are installed on ships or in the vicinity of port areas to measure the amount of pollutants being emitted. Although it provides very accurate data, this approach involves high costs and requires specialized equipment. Another methodology is the fuel consumption-based emission inventory, which uses data declared by ship operators. However, this approach may be affected by inconsistencies in reporting and does not always provide precise emission estimates for specific ship activities and operating conditions. In this work, emissions are estimated using available data, including technical characteristics (such as gross tonnage, engine power, etc.) and ship operational information (such as arrival and departure times, dwell time, etc.). Special attention is paid to the time at hoteling, i.e. the period during which the auxiliary engines remain active while the ship is at hoteling, as it contributes significantly to the total emissions. The estimation is based on regression curves and considers variables such as load factor and pollutant-specific emission factors. The necessary information was obtained from databases such as the Automatic Identification System (AIS) and international studies. In this context, the port of Catania was chosen as a case study to analyze the contribution of Ro-Ro ships to local emissions. This type of ship, used to transport vehicles and rolling stock, is among the main sources of pollution. Estimates show that fuel consumption and emissions vary significantly depending on the size and frequency of ship trips, highlighting the importance of targeted strategies to reduce environmental impact. This analysis thus provides a useful framework for understanding the dynamics of maritime pollution and represents a first step towards a more detailed and in-depth quantification of emissions, taking the selected case study as a reference
Questioni di budget militare nell'impero tardo antico
No full textLa tesi propone un'analisi quantitativa del budget militare tardo antico. Il lavoro tenta dapprincipio calcolare il numero di soldati che componevano l'esercito tra IV e V secolo attraverso una comparazione tra i dati della Notitia Dignitatum e i riscontri archeologici del limes tardo antico. In secondo luogo, attraverso una ricostruzione degli emolumenti ricevuti dai soldati, si tenta una quantificazione del budget militare che è costituito dalla retribuzione in moneta e da quella in natura
Teaching Design of Reinforced Concrete Structures through Laboratory Activities
No full textCourses in design of reinforced concrete structures given by the Faculty of Architecture and the Faculty of Civil Engineering of
Sapienza University of Rome usually take the form of traditional lectures, exercises, and project work. This article presents the initial results
of a project started in 2019 that aims to use, as an auxiliary teaching tool for these courses, hands-on experiences in laboratory involving
design, construction, and failure tests of small-scale reinforced concrete elements. The objective is to enhance students’ understanding of the
physical behavior of structures and the principles of structural design through a more holistic approach. To achieve this, educational laboratory
experiences are introduced to supplement traditional frontal lecture courses on reinforced concrete structures. The effectiveness on the
students’ preparation and involvement in the activities was found to be positive. Even though the activities were voluntary and there were no
extra credit opportunities, all students participated, indicating strong interest
Hybrid computational approaches for the elucidation of complex biocatalytic mechanisms
No full textWe report two mechanistic investigations on recently discovered, industrially relevant biocatalytic systems conducted using a hybrid computational approach integrating Quantum Mechanics/Molecular Mechanics (QM/MM) with the Molecular Dynamics/Perturbed Matrix Method (MD-PMM). In the first study, concerning the reduction of 2-pentanone catalyzed by the Horse Liver Alcohol Dehydrogenase (HLADH) in the presence of the biomimetic cofactor, benzyl-1,4-dihydronicotinamide (BNAH), we propose a revised mechanism that follows a sequential pathway in which an endothermic hydride transfer (HT) precedes a strongly exothermic proton transfer (PT).
The Gibbs free-energy barrier for HT, calculated using MD-PMM, is 14 kcal mol−1, in excellent agreement with the value derived from experimental data. The protein environment is found to be responsible for lowering the energy barrier compared to the gas phase. A plausible PT pathway is hypothesized in which His51 is first protonated from the bulk solvent and then relays the proton via a bridging water molecule to the oxygen atom of Ser48 and subsequently to the substrate carbonyl. One or more water molecules forming a hydrogen-bond network between His51 and Ser48 are essential to activate the proton transfer chain.
The second study focuses on fatty acid photodecarboxylase from Chlorella variabilis (CvFAP), a recently discovered flavin adenine dinucleotide (FAD)-containing photoenzyme that catalyzes the light-driven decarboxylation of long-chain fatty acids into the corresponding alkanes, a reaction of considerable relevance for biofuel production. Despite its remarkable biotechnological potential, the mechanistic pathway of this transformation remains only partially understood, encompassing uncertainties about the protonation state of the substrate, the origin of the unusual features in the enzyme’s FAD absorption spectrum (which exhibits the main absorption peaks red-shifted by
approximately 10–15 nm compared with those observed in other flavoproteins), and the nature of the red-shifted FAD species (FADRS) observed experimentally after decarboxylation.
Our QM/MM calculations strongly indicate that the bound fatty acid exists predominantly in its deprotonated form. Building on this result, the FAD absorption spectrum in CvFAP was simulated using MD–PMM calculations, which show that the contribution of flavin conformational bending to the observed red shift is minor (4 nm),
whereas the protein environment is the dominant factor (15 nm). Regarding the origin of the FADRS species, our calculations support the hypothesis that its formation is likely driven by a pronounced reorganization of the active site following product formation (alkane, CO2, and bicarbonate), with the bicarbonate interacting strongly with the FAD moiety.
Our results provide a solid basis for understanding the reaction mechanisms of these enzymes, offering mechanistic insights that could inform future environmentally friendly industrial applications. Moreover, from a computational point of view, this thesis demonstrates the complementarity of the two methodologies (QM/MM and MD–PMM) used here highlighting that their integration is fundamental for achieving a detailed and accurate characterization of enzymatic reaction mechanisms
A new technology for termite-proof underground cables. Proposing novel solutions
No full textThis article highlights the significant termite damage problem affecting buried power lines in utility-scale photovoltaic (PV) plants. It emphasizes the risks posed by insulation failures, which can lead to service interruptions and damage to equipment, as documented in a real example plant in Brazil. The article outlines the required tests to identify the failure points critical for preventing further damage. The authors propose various solutions to mitigate the problem, including Tratos’ development of a reinforced medium-voltage (MV) cable designed to withstand damage from termites and rodents. This cable includes a specialized fiberglass covering, which has been tested at the solar facility. It showed promising results in preventing damage and improving the overall durability of the system. By addressing this issue, the article contributes to advancing infrastructure resilience in solar energy systems, making them more reliable
On the use of mean square error and directional forecast accuracy for model selection: a simulation study
No full text{Monte Carlo simulations are used to determine the weights of a procedure that combines the mean square error and directional forecast accuracy criteria for model selection.} We propose a new simple procedure for model selection based on simultaneously targeting
the mean square error and directional forecast accuracy criteria. The procedure combines the two types of accuracy measures using a weighting scheme for the selection of the forecasting models. Monte Carlo analysis under different scenarios serves as a tool
that assesses the strength of the procedure. To this end, we consider various time series models as generation mechanisms, such as time-homogeneous univariate and vector autoregressions. We focus on an important but specific aspect of forecast model specification, that is forecast model selection which chooses one out of two rival models, both of them evaluated over a training sample. For the evaluation of the training samples, we use rolling and recursive estimation schemes. The performance of the proposed procedure is quite heterogeneous across designs. However, while finding powerful
tools for improving directional accuracy remains a challenge, the new procedure deserves some credits
The Hydromechanic Approach to Complex Diffusion. Hydrogels as a Model System
No full textA tiny particle, just a few micrometers in size, when suspended in a liquid at rest, never remains
still. Instead, it moves in an irregular and unceasing way: this is what is known as Brownian
motion. It is characterized by a linear scaling of the mean squared displacement (MSD) together
with Gaussian displacement distributions. In complex fluids, however, systematic deviations from
these signatures have been widely observed, involving either both behaviors simultaneously or
each one individually.
Understanding the physical origin of these anomalies, that we may term complex diffusion
phenomena, opens new avenues for exploring the microscopic dynamics that govern transport
and relaxation processes in heterogeneous media. Such an understanding is crucial not only for
unveiling the fundamental mechanisms underlying molecular motion in biological systems, but
also for developing a unified framework to describe transport in soft matter, disordered materials,
and active or viscoelastic environments.
Most models used to describe these deviations rely on generalizations of the classical random
walk, effectively performing a coarse-graining of the fluid’s reaction on the particle. This influence
manifests itself in the specific form of the deviation from the standard random walk behavior,
yet it remains implicit in the model formulation and is not directly represented in its physical
structure.
Including explicitly the coupling between the fluid and the particle means adopting a hydromechanic
approach, that is, the study of the interactions between fluids and solid bodies in order to derive
the mechanics of the bodies resulting from the fluid reaction, and the hydrodynamics of the fluid
resulting from the reaction of the bodies. In this thesis, focusing on the first of these two aspects,
we present, for the first time, a systematic formulation of the hydromechanic approach to complex
diffusion.
This objective is developed across the first three chapters, each presenting a set of original results.
In the second Chapter (following the introductive one), we introduce a three-signature analysis,
encompassing the MSD, displacement distributions, and the velocity autocorrelation function
(VACF), that for the first time maps qualitative experimental patterns to specific particle–fluid
interaction mechanisms. It should be noted that, at present, VACFs can be reliably measured only
in simple fluids; however, it is reasonable to expect that in the coming years this quantity will
also become experimentally accessible in complex fluids. In the third Chapter, we propose a new
fluctuation–dissipation relation, termed the Global Effective Fluctuation–Dissipation Relation,
which links the long-term diffusion coefficient to the effective friction factor. This relation is
designed to be readily testable in laboratory conditions and provides a discriminating tool among
different interpretative models of particle motion. Finally, in the fourth Chapter, we employ the
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hydromechanic approach to derive the first theoretical explanation of the phenomenon known as
Fickian yet non-Gaussian diffusion (FnGD) in the regime where the particle perceives the fluid as
complex yet homogeneous. This result is of fundamental importance, as it provides for the first
time a mechanistic explanation of the phenomenon when the particle size is such that it does not
directly probe the medium’s heterogeneity. The same chapter also includes a first concise review
of the main experimental results on FnGD reported to date.
The second part of the thesis turns to a model system for complex diffusion: hydrogels (cross-
linked polymer networks that retain large amounts of water while exhibiting soft, viscoelastic,
and poroelastic behavior). Specifically, the fifth chapter explores nanoparticle transport within
physically cross-linked alginate hydrogels, used here as tissue-mimicking materials, through epi-
fluorescence microscopy. We analyze particle motion across increasing cross-linking levels, tuned by
raising salt concentration. We introduce a new MSD-based classifier that segments trajectories into
trapping, linear, and anomalous regimes, enabling direct comparison between low- and high-salt
conditions. With stronger cross-linking, we observe the survival of only the faster subpopulation
and a higher fraction of trapped particles. Finally, in the sixth Chapter we propose the first method
to infer accessible porosity directly from standard z-projections by recasting anomalous transport
into an effective Brownian clock: each connected accessible cluster is assigned an anomalous
exponent as a proxy for local porosity. We quantify information loss due to finite depth of field
away from the quasi-2D regime and provide practical rules to trade volumetric coverage against
axial occlusion. The framework delivers conservative upper/lower bounds on porosity that tighten
with longer acquisitions or complementary channels. As a separate contribution, we present what
appears to be the first derivation of the Hausdorff dimension for an anomalous stochastic process