Peptide- and protein-based therapeutics are becoming a promising treatment regimen for myriad diseases. Toxicity of proteins is the primary hurdle for protein-based therapies. Thus, there is an urgent need for accurate in silico methods for determining toxic proteins to filter the pool of potential candidates. At the same time, it is imperative to precisely identify non-toxic proteins to expand the possibilities for protein-based biologics. To address this challenge, we proposed an ensemble framework, called VISH-Pred, comprising models built by fine-tuning ESM2 transformer models on a large, experimentally validated, curated dataset of protein and peptide toxicities. The primary steps in the VISH-Pred framework are to efficiently estimate protein toxicities taking just the protein sequence as input, employing an under sampling technique to handle the humongous class-imbalance in the data and learning representations from fine-tuned ESM2 protein language models which are then fed to machine learning techniques such as Lightgbm and XGBoost. The VISH-Pred framework is able to correctly identify both peptides/proteins with potential toxicity and non-toxic proteins, achieving a Matthews correlation coefficient of 0.737, 0.716 and 0.322 and F1-score of 0.759, 0.696 and 0.713 on three non-redundant blind tests, respectively, outperforming other methods by over on these quality metrics. Moreover, VISH-Pred achieved the best accuracy and area under receiver operating curve scores on these independent test sets, highlighting the robustness and generalization capability of the framework. By making VISH-Pred available as an easy-to-use web server, we expect it to serve as a valuable asset for future endeavors aimed at discerning the toxicity of peptides and enabling efficient protein-based therapeutics.

The field of precision radiation therapy has seen remarkable advancements in both experimental and computational methods. Recent literature has introduced various approaches such as Spatially Fractionated Radiation Therapy (SFRT). This unconventional treatment, demanding high-precision radiotherapy, has shown promising clinical outcomes. A comprehensive computational scheme for SFRT, extrapolated from a case report, is proposed. This framework exhibits exceptional flexibility, accommodating diverse initial conditions (shape, inhomogeneity, etc.) and enabling specific choices for sub-volume selection with administrated higher radiation doses. The approach integrates the standard linear quadratic model and, significantly, considers the activation of the immune system due to radiotherapy. This activation enhances the immune response in comparison to the untreated case. We delve into the distinct roles of the native immune system, immune activation by radiation, and post-radiotherapy immunotherapy, discussing their implications for either complete recovery or disease regrowth.

Antimicrobial resistance prediction is a pivotal ongoing research activity that is currently being explored across various levels. In this context, we present the application of two prediction methods that model the antimicrobial resistance of Neisseria gonorrhoeae on the national level as an outcome of socio-economic processes. The methods use two different implementations of the principal component analysis combined with classification algorithms. Using these two methods, we generated forecasts concerning antimicrobial resistance of Neisseria gonorrhoeae, using publicly available databases encompassing over 200 countries from 1998 to 2021. Both approaches exhibit similar mean absolute averages and correlations when comparing available measurements with predictions. Steps of statistical analysis and applications are discussed, including population-weighted central tendencies, geographical correlations, time trends and error reduction possibilities.

A fundamental challenge for personalized medicine is to capture enough of the complexity of an individual patient to determine an optimal way to keep them healthy or restore their health. This will require personalized computational models of sufficient resolution and with enough mechanistic information to provide actionable information to the clinician. Such personalized models are increasingly referred to as medical digital twins. Digital twin technology for health applications is still in its infancy, and extensive research and development is required. This article focuses on several projects in different stages of development that can lead to specific—and practical–medical digital twins or digital twin modeling platforms. It emerged from a two-day forum on problems related to medical digital twins, particularly those involving an immune system component. Open access video recordings of the forum discussions are available.

Introduction While radiotherapy has long been recognized for its ability to directly ablate cancer cells through necrosis or apoptosis, radiotherapy-induced abscopal effect suggests that its impact extends beyond local tumor destruction thanks to immune response. Cellular proliferation and necrosis have been extensively studied using mathematical models that simulate tumor growth, such as Gompertz law, and the radiation effects, such as the linear-quadratic model. However, the effectiveness of radiotherapy-induced immune responses may vary among patients due to individual differences in radiation sensitivity and other factors.Methods We present a novel macroscopic approach designed to quantitatively analyze the intricate dynamics governing the interactions among the immune system, radiotherapy, and tumor progression. Building upon previous research demonstrating the synergistic effects of radiotherapy and immunotherapy in cancer treatment, we provide a comprehensive mathematical framework for understanding the underlying mechanisms driving these interactions.Results Our method leverages macroscopic observations and mathematical modeling to capture the overarching dynamics of this interplay, offering valuable insights for optimizing cancer treatment strategies. One shows that Gompertz law can describe therapy effects with two effective parameters. This result permits quantitative data analyses, which give useful indications for the disease progression and clinical decisions.Discussion Through validation against diverse data sets from the literature, we demonstrate the reliability and versatility of our approach in predicting the time evolution of the disease and assessing the potential efficacy of radiotherapy-immunotherapy combinations. This further supports the promising potential of the abscopal effect, suggesting that in select cases, depending on tumor size, it may confer full efficacy to radiotherapy.

Leishmania spp. commonly infects phagocytic cells of the immune system, particularly macrophages, employing various immune evasion strategies that enable their survival by altering the intracellular environment. In mammals, these parasites establish persistent infections by modulating gene expression in macrophages, thus interfering with immune signaling and response pathways, ultimately creating a favorable environment for the parasite’s survival and reproduction. In this study, our objective was to use data mining and subsequent filtering techniques to identify the genes that play a crucial role in the infection process of Leishmania spp. We aimed to pinpoint genes that have the potential to influence the progression of Leishmania infection. To achieve this, we exploited prior, curated knowledge from major databases and constructed 16 datasets of human molecular information consisting of coding genes and corresponding proteins. We obtained over 400 proteins, identifying approximately 200 genes. The proteins coded by these genes were subsequently used to build a network of protein–protein interactions, which enabled the identification of key players; we named this set Predicted Genes. Then, we selected approximately 10% of Predicted Genes for biological validation. THP-1 cells, a line of human macrophages, were infected with Leishmania major in vitro for the validation process. We observed that L. major has the capacity to impact crucial genes involved in the immune response, resulting in macrophage inactivation and creating a conducive environment for the survival of Leishmania parasites.

Spatial color algorithms (SCAs) are algorithms grounded in the retinex theory of color sensation that, mimicking the human visual system, perform image enhancement based on the spatial arrangement of the scene. Despite their established role in image enhancement, their potential as dequantizers has never been investigated. Here, we aim to assess the effectiveness of SCAs in addressing the dual objectives of color dequantization and image enhancement at the same time. To this end, we propose the term dequantenhancement. In this paper, through two experiments on a dataset of images, SCAs are evaluated through two distinct pathways: first, quantization followed by filtering to assess both dequantization and enhancement; and second, filtering applied to original images before quantization as further investigation of mainly the dequantization effect. The results are presented both qualitatively, with visual examples, and quantitatively, through metrics including the number of colors, retinal-like subsampling contrast (RSC), and structural similarity index (SSIM).

Precision Viticulture (PV) is becoming an active and interdisciplinary research field since it requires solving interesting research issues to concretely answer the demands of specific use cases. A challenging problem in this context is the development of automatic methods for yield estimation. Computer vision methods can contribute to the accomplishment of this task, especially those that can replicate what winemakers do manually. In this paper, an automatic artificial intelligence method for grape bunch detection from RGB images is presented. A customized Convolutional Neural Network (CNN) is employed for pointwise classification of image pixels and the dependence of classification results on the type of input color channels and grapes color properties are studied. The advantage of using additional perception-based input features, such as luminance and visual contrast, is also evaluated, as well as the dependence of the method on the choice of the training set in terms of the amount of labeled data. The latter point has a significant impact on the practical use of the method on-site, its usability by non-expert users, and its adaptability to individual vineyards. Experimental results show that a properly trained CNN can discriminate and detect grape bunches even under uncontrolled acquisition conditions and with limited computational load, making the proposed method implementable on smart devices and suitable for on-site and real-time applications.

A nonlinear crime model is generalized by introducing self- and cross-diffusion terms. The effect of diffusion on the stability of non-negative constant steady states is applied. In particular, the cross-diffusion-driven instability, called Turing instability, is analyzed by linear stability analysis, and several Turing patterns driven by the cross-diffusion are studied through numerical investigations. When the Turing–Hopf conditions are satisfied, the type of instability highlighted in the ODE model persists in the PDE system, still showing an oscillatory behavior.

This Special Issue of Applied Numerical Mathematics contains selected and refereed papers presented at the 21st IMACS World Congress which was held during September 11–15, 2023 in Rome, Italy.

We study the process of thermal convection in jammed emulsions with a yield-stress rheology. We find that heat transfer occurs via an intermittent mechanism, whereby intense short-lived convective “heat bursts” are spaced out by long-lasting conductive periods. This behavior is the result of a sequence of fluidization-rigidity transitions, rooted in a nontrivial interplay between emulsion yield-stress rheology and plastic activity, which we characterize via a statistical analysis of the dynamics at the droplet scale. We also show that droplets’ coalescence induced during heat bursts leads to a spatially heterogeneous phase inversion of the emulsion which eventually supports a sustained convective state.

The paper concerns the weighted Hilbert transform of locally continuous functions on the semiaxis. By using a filtered de la Vallée Poussin type approximation polynomial recently introduced by the authors, it is proposed a new “truncated” product quadrature rule (VP- rule). Several error estimates are given for different smoothness degrees of the integrand ensuring the uniform convergence in Zygmund and Sobolev spaces. Moreover, new estimates are proved for the weighted Hilbert transform and for its approximation (L-rule) by means of the truncated Lagrange interpolation at the same Laguerre zeros. The theoretical results are validated by the numerical experiments that show a better performance of the VP-rule versus the L-rule.

We are concerned with the uniform approximation of functions of a generic reproducing kernel Hilbert space (RKHS). In this general context, classical approximations are given by Fourier orthogonal projections (if we know the Fourier coefficients) and their discrete versions (if we know the function values on well-distributed nodes). In case such approximations are not satisfactory, we propose to improve the approximation using the same data but combined with a new kernel function. For the resulting (both continuous and discrete) new approximations, theoretical estimates and concrete examples are given.

In this paper the interpolating rational functions introduced by Floater and Hormann are generalized leading to a whole new family of rational functions depending on γ, an additional positive integer parameter. For γ=1, the original Floater–Hormann interpolants are obtained. When γ>1 we prove that the new rational functions share a lot of the nice properties of the original Floater–Hormann functions. Indeed, for any configuration of nodes in a compact interval, they have no real poles, interpolate the given data, preserve the polynomials up to a certain fixed degree, and have a barycentric-type representation. Moreover, we estimate the associated Lebesgue constants in terms of the minimum (h∗) and maximum (h) distance between two consecutive nodes. It turns out that, in contrast to the original Floater–Hormann interpolants, for all γ>1 we get uniformly bounded Lebesgue constants in the case of equidistant and quasi-equidistant nodes configurations (i.e., when h∼h∗). For such configurations, as the number of nodes tends to infinity, we prove that the new interpolants (γ>1) uniformly converge to the interpolated function f, for any continuous function f and all γ>1. The same is not ensured by the original FH interpolants (γ=1). Moreover, we provide uniform and pointwise estimates of the approximation error for functions having different degrees of smoothness. Numerical experiments illustrate the theoretical results and show a better error profile for less smooth functions compared to the original Floater–Hormann interpolants.

The paper is concerned with a generalization of Floater–Hormann (briefly FH) rational interpolation recently introduced by the authors. Compared with the original FH interpolants, the generalized ones depend on an additional integer parameter γ>1, that, in the limit case γ=1 returns the classical FH definition. Here we focus on the general case of an arbitrary distribution of nodes and, for any γ>1, we estimate the sup norm of the error in terms of the maximum (h) and minimum (h∗) distance between two consecutive nodes. In the special case of equidistant (h=h∗) or quasi–equidistant (h≈h∗) nodes, the new estimate improves previous results requiring some theoretical restrictions on γ which are not needed as shown by the numerical tests carried out to validate the theory.

Quasiparticles are low-energy excitations with important roles in condensed matter physics. An intriguing example is provided by Majorana quasiparticles, which are equivalent to their antiparticles. Despite being implicated in neutrino oscillations and topological superconductivity, their experimental realizations remain very rare. Here, we propose a purely classical realization of Majorana fermions in terms of three-dimensional disclination lines in active nematics. The underlying reason is the well-known equivalence, in 3D, between a + 1 / 2 local defect profile and a - 1 / 2 profile, which acts as its antiparticle. The mapping also requires proving that defect profiles transform as spinors, and activity is needed to overcome the elastic cost associated with these excitations, so they spontaneously appear in steady state. We combine topological considerations and numerics to show that active nematics under confinement spontaneously create in their interior topologically charged disclination lines and loops, akin to Majorana quasiparticles with finite momentum. Within a long channel, the phenomenology we observe resembles that of the Kitaev chain, as Majorana-like states appear near the boundaries, while a delocalized topological excitation arises in the form of a chiral disclination line. The analogy between 3D nematic defects and topological quasiparticles further suggests that active turbulence can be viewed as a topological phase, where defects percolate to form delocalized topological quasiparticles similar to those observed in the channel. We propose that three-dimensional active disclinations can be used to probe the physics of Majorana spinors at much larger scale than that for which they were originally introduced, potentially facilitating their experimental study.

High-resolution water vapor fields retrieved over Iberia during the passage of storm Barbara (October 19–20, 2020) by Sentinel-1 and assimilated by the Weanther Research & Forecasting Model (WRF) reveal a substantial positive impact on water vapor forecasting. Due to the path followed by the storm across Iberia, from its southwestern to the northeastern corners, and the geometry of Sentinel-1 data acquisition, it is possible to show, for the first time, the potential added value of precipitable water vapor (PWV) obtained by the Interferometric Synthetic-Aperture Radar (InSAR) technique, as a data source for both the forecast and validation of meteorological forecasts of synoptic-scale storms. Results indicate that data assimilated in the InSARfootprint positively impact the downstream forecasts up to the northeastern boundary, about 850km and 12 hours away, with improved skill scores of the water vapor distribution and improved forecasts of rain.

This article presents a study of the relationship among decorrelation phase in synthetic aperture radar (SAR) interferogram, soil moisture, and water content in vegetation with the aim of mitigating the contribution of decorrelation phase in SAR interferometry estimates of terrain displacements. A methodology for the mitigation of the phase bias based on the temporal variation of the vegetation water content is presented. Decorrelation phases are computed using time series of Sentinel-1 images and compared with in situ measurements of soil moisture. It is shown that soil moisture can partially explain the observed values of decorrelation phases pointing out the role of vegetation water content. A new model is proposed to compute the contribution of vegetation to the decorrelation phase based on the normalized difference water index (NDWI) index. The methodology is applied to all short temporal baseline interferograms obtained from the time series of Sentinel-1 SAR images, using the NDWI maps generated from Sentinel-2 multispectral images. The cumulative displacement is computed by integrating the short temporal baseline interferograms, corrected for the land cover and soil moisture changes. It is shown that the proposed methodology can reduce the variance of estimated cumulative displacement in areas covered by vegetation.

Accuracy of radar interferometry is often hindered by the atmospheric phase screen (APS). To address this limitation, the geostatistical approach known as Kriging has been employed to predict APS from sparse observations for compensation purposes. In this article, we propose an enhanced Kriging approach to achieve more accurate APS predictions in ground-based (GB) radar interferometry applications. Specifically, the Kriging system is augmented with a time-series measure through correlation analysis, effectively leveraging spatiotemporal information for APS prediction. The validity of the introduced Kriging method in the APS compensation framework was tested with Ku-band GB radar datasets collected over two different mountainous sites. A comparison of this method with simple Kriging reveals a noticeable improvement in APS prediction accuracy and temporal phase stability.

We study the sub-ionospheric VLF transmitter signals recorded by the Austrian Graz station in the year 2020. Those radio signals are known to propagate in the Earth-ionosphere waveguide between the ground and lower ionosphere. The Austrian Graz facility (geographic coordinates: 15.46 degrees E, 47.03 degrees N) can receive such sub-ionospheric transmitter signals, particularly those propagating above earthquake (EQ) regions in the southern part of Europe. We consider in this work the transmitter amplitude variations recorded a few weeks before the occurrence of two EQs in Croatia at a distance less than 200 km from Graz VLF facility. The selected EQs happened on 22 March 2020 and 29 December 2020, with magnitudes of Mw5.4 and Mw6.4, respectively, epicenters localized close to Zagreb (16.02 degrees E, 45.87 degrees N; 16.21 degrees E, 45.42 degrees N), and with focuses of depth smaller than 10 km. In our study we emphasize the anomaly fluctuations before/after the sunrise times, sunset times, and the cross-correlation of transmitter signals. We attempt to evaluate and to estimate the latitudinal and the longitudinal expansions of the ionospheric disturbances related to the seismic preparation areas.