FPU phenomenon for generic initial data

The well known FPU phenomenon (lack of attainment of equipartition of the mode--energies at low energies, for some exceptional initial data) suggests that the FPU model does not have the mixing property at low energies. We give numerical indications that this is actually the case. This we show by computing orbits for sets of initial data of full measure, sampled out from the microcanonical ensemble by standard Montecarlo techniques. Mixing is tested by looking at the decay of the autocorrelations of the mode--energies, and it is found that the high--frequency modes have autocorrelations that tend instead to positive values. Indications are given that such a nonmixing property survives in the thermodynamic limit. It is left as an open problem whether mixing obtains within time--scales much longer than the presently available ones

IN SILICO IDEOTYPING: DEFINITION AND EVALUATION OF RICE IDEOTYPES IMPROVED FOR RESISTANCE/TOLERANCE TRAITS TO BIOTIC AND ABIOTIC STRESSORS UNDER CLIMATE CHANGE SCENARIOS

The development of new cultivars better adapted to specific growing conditions is a key strategy to meet an ever-increasing growing global food demand and search for more sustainable cropping systems. This is even more crucial in the context of a changing climate. Ecophysiological models and advanced computational techniques (e.g., sensitivity analysis, SA) represent powerful tools to analyze genotype (G) by environment (E) interactions, thus supporting breeders in identifying key traits for specific agro-environmental contexts. However, limits for the effective use of mathematical models within breeding programs are represented by the uncertainty in the distribution of plant trait values, the lack of processes dealing with resistance/tolerance traits in most ideotyping studies, the partial suitability of current crop models for ideotyping purposes, and the absence of modelling tools directly usable by breeders. The aim of this research was to address these issues improving methodologies already in use, proposing new paradigms for the development of crop models explicitly targeting ideotyping applications and developing tools that would encourage a deep interaction of the modelling and breeding communities. The focus was on rice, for its role as staple food for more than a half of world\u2019s population, and on resistance/tolerance traits to biotic/abiotic stressors, for their central role in increasing crop adaptation. Moreover, current conditions and climate change projections were considered, to support the definition of strategies for breeding in the medium-long term. A standard procedure to quantify 12 and manage 12 the impact of the uncertainty in the distribution of plant trait values was developed, using the WARM rice model and the Sobol\u2019 method as case study. The approach is based on a SA (generating sample of parameter distributions) of a SA (generating samples of parameters for each generated distribution) using distributions of jackknife statistics calculated on literature values to reproduce the uncertainty in defining parameters distributions. As a practical implication, the procedure developed allows identifying plant traits whose uncertainty in distribution can alter ideotyping results, i.e., traits whose distributions could need to be refined. Global SA was then used to identify rice traits putatively producing the largest yield benefits in five contrasting districts in the Philippines, India, China, Japan and Italy. The analysis involved phenotypic traits dealing with light interception, photosynthetic efficiency, tolerance to abiotic stressors, resistance to fungal pathogens and grain quality. Results suggested that breeding for traits involved with disease resistance and tolerance to cold- and heat-induced spikelet sterility could provide benefits similar to those obtained from improving traits affecting potential yield. Instead, advantages resulting from varying traits involved with grain quality were markedly frustrated by inter-annual weather variability. Since results highlighted strong G 7E interactions, a new index to derive district-specific ideotypes was developed. Given the key role of biotic/abiotic stressors in determining actual yield and the deep impact of related G 7E interactions, a study was carried out by explicitly focusing on the definition of rice ideotypes improved for their resistance to fungal pathogens and tolerance to abiotic constraints (temperature shocks inducing sterility). The analysis was carried out at district level with a high spatial resolution (5 km 7 5 km elementary simulation unit), targeting the improvement of the most representative 34 varieties in six Italian rice districts. Genetic improvement was simulated via the introgression of traits from donor varieties. Results clearly showed that breeders should focus on increasing resistance to blast disease, as this appears as a factor markedly limiting rice yields in Italy, regardless of the districts and climate scenarios, whereas benefits deriving from improving tolerance to cold-induced sterility could be markedly affected by G 7E interactions. To reduce the risk of discrepancies between in silico ideotypes and their in vivo realizations, both studies involved only model parameters with a close relationship with phenotypic traits breeders are working on. However, a long-term strategy to overcome limitations related with the partial suitability of available models would be building new ideotyping-specific models explicitly around traits involved in breeding programs. This proposal for a paradigm shift in model development was illustrated taking salt stress tolerance and rice as a case study. Dedicated growth chamber experiments were conducted to develop a new model explicitly accounting for tolerance traits modulating Na+ uptake and distribution in plant tissues, as well as the impact of the accumulated Na+ on photosynthesis, senescence and spikelet sterility. An ideotyping study was conducted at two sites (in Greece and California) characterized by different seasonal dynamics of salinity in field water. Results showed how, under different scenarios, traits assuring the largest contribution to the overall tolerance could refer to completely different physiological mechanisms: tissue tolerance in one case, sodium exclusion in the other. This encourages the development of explicit trait-based approaches to increase the integration of crop models within breeding programs. A parallel path to achieve this goal is the development of modelling platforms targeting breeders as final users, who does not have necessarily in-depth skills in crop modelling and IT. The platform ISIde, derived from a close collaboration between target users, biophysical modelers and IT specialists, represents the first prototype of a platform specifically developed for being used directly by breeders to evaluate in silico improved varieties at district level. This thesis demonstrated the usefulness of simulation models for the definition of ideotypes for specific agro-environmental conditions. Targeting ideotyping applications, new methodologies, paradigms for model development and modelling tools were developed, thus contributing to improve the potential of crop modelling to support breeding programs. Future developments will target researches aimed at overcoming the limits behind this study, i.e., (i) absence of explicit interactions between traits, (ii) no adaptation strategies considered, and (iii) lack of approaches for the simulation of the evolutionary potential of pathogens in response to long-term climate variations and increased host resistance

Tailoring parameter distributions to specific germplasm : impact on crop model-based ideotyping

Crop models are increasingly used to identify promising ideotypes for given environmental and management conditions. However, uncertainty must be properly managed to maximize the in vivo realizability of ideotypes. We focused on the impact of adopting germplasm-specific distributions while exploring potential combinations of traits. A field experiment was conducted on 43 Italian rice varieties representative of the Italian rice germplasm, where the following traits were measured: light extinction coefficient, radiation use efficiency, specific leaf area at emergence and tillering. Data were used to derive germplasm-specific distributions, which were used to re-run a previous modelling experiment aimed at identifying optimal combinations of plant trait values. The analysis, performed using the rice model WARM and sensitivity analysis techniques, was conducted under current conditions and climate change scenarios. Results revealed that the adoption of germplasm-specific distributions may markedly affect ideotyping, especially for the identification of most promising traits. A re-ranking of some of the most relevant parameters was observed (radiation use efficiency shifted from 4th to 1st), without clear relationships between changes in rankings and differences in distributions for single traits. Ideotype profiles (i.e., values of the ideotype traits) were instead more consistent, although differences in trait values were found

Analysis and modeling of processes involved with salt tolerance and rice

Salinity is a worldwide problem for rice (Oryza sativa L.) cultivation, and a number of breeding programs targeting increased salt tolerance are ongoing. A new trait-based mathematical model for salt stress on rice was recently proposed, characterized by a high level of detail in the description of physiological mechanisms dealing with crop response to salinity. In this study, dedicated growth chamber experiments were performed where three rice cultivars with different degrees of tolerance were grown under different salinity levels. The aim was to improve the understanding of physiological mechanisms like Na+ uptake and sequestration in structural tissues, and to validate the model using new datasets where temporal dynamics in plant response to salt stress were analyzed. Model evaluation demonstrated strong agreement between measured and simulated dry weights of plant organs (e.g., R2 = 0.88-0.97 for aboveground biomass), [Na+] in plant tissues (R2 = 0.73-0.88), and green leaf area index (R2 = 0.71-0.99). These results demonstrate the reliability of the model and support its adoption within studies aimed at analyzing or predicting the response of different cultivars to temporal dynamics of Na+ concentration in soil and water

Effect of three larval diets on the development of the armyworm, Spodoptera latifascia Walker, 1856 (Noctuidae, Lepidoptera)

Some biological effects of feeding larvae of the armyworm Spodoptera latifascia with leaves of three plant species (cotton, soybean and lettuce) have been studied. Some indicative measurements were utilized to determine the host suitability of these three plant species. Cotton leaves (Gossypium hirsutum) were found to be better than soybean (Glycine max) for the development and growth of this insect. Lettuce leaves (Lactuca sativa) were incapable of sustaining this insect. Moreover, the stress of the latter diet was associated with a latent microbial disease, a mixed infection caused by Vairimorpha sp. and a nuclear polyhedrosis virus (NPV). Cotton leaves can be recommended as a suitable diet for mass rearing of this insect species. Due to recent outbreks of S. latifascia observed in the States of São Paulo, Santa Catarina and Paraná and because of the frequent applications of wide spectrum chemical insecticides, it can be expected that this insect will soon become one of the important pests threatening cotton and other economic plantations in Brazil.17718

Why small particle fixed dose triple therapy? An excursus from COPD pathology to pharmacological treatment evolution

Although bronchodilators are the cornerstone in chronic obstructive pulmonary disease (COPD) therapy, the treatment with a single-agent bronchodilator may not provide adequate symptoms control in COPD. The combination of drugs with different mechanisms of action may be more effective in inducing bronchodilation and preventing exacerbations, with a lower risk of side-effects in comparison with the increase of the dose of a single molecule. Several studies comparing the triple therapy with the association of long-acting ß2 agonist (LABA)/inhaled corticosteroid (ICS) or long-acting muscarinic antagonist (LAMA)/LABA reported improvement of lung function and quality of life. A significant reduction in moderate/severe exacerbations has been observed with a fixed triple combination of beclometasone dipropionate (BDP), formoterol fumarate (FF) and glycopyrronium (G) in a single inhaler. The TRILOGY, TRINITY and TRIBUTE studies have provided confirming evidence for a clinical benefit of triple therapy over ICS/LABA combination treatment, LAMA monotherapy and LABA/LAMA combination, with prevention of exacerbations being a key finding. A pooled post hoc analysis of the published clinical studies involving BDP/FF/G fixed combination demonstrated a reduction in fatal events in patients treated with ICS-containing medications, with a trend of statistical significance [hazard ratio = 0.72, 95% confidence interval (CI) 0.50–1.02, p = 0.066], that becomes significant if we consider reduction in fatal events for non-respiratory reasons (hazard ratio = 0.65, 95% CI 0.43–0.97, p = 0.037). In conclusion, a fixed combination of more drugs in a single inhaler can improve long-term adherence to the therapy, reducing the risk of exacerbations and hospital resources utilization. The twice a day administration may provide a better coverage of night, particularly in COPD patients who are highly symptomatic. The inhaled extrafine formulation that allows drug deposition in both large and small – peripheral – airways, is the value added

EU-Funded Telemedicine Projects – Assessment of, and Lessons Learned From, in the Light of the SARS-CoV-2 Pandemic

The SARS-CoV-2 health emergency has demonstrated the need for developing structured telemedicine systems to protect citizens from the spread of the virus. Thereby, their importance and the necessity to tailor their diffusion at large scale for providing services both at a distance and in time has been shown. For these reasons, the European Union advocates the digital transition of health systems for the next 5 years. The main aim of this work is to revisit the telemedicine research projects financed by European Community during the period 2000-2020 with particular respect to the results derived from their application. The analysis showed that some integration of tele-care and tele-health could be obtained with tele-monitoring systems and the implementation of Electronic Personal Record (EPR). Furthermore, telemedicine allows enhancing health care in critical environments, to protect health and life of the most vulnerable patients, and to encourage cross-border dialogue. The criteria of “from distance” and “timely delivered” are granted, but the effectiveness of the overall offered services highly depends on the availability and the quality of the input data. Unfortunately, this remains a relevant problem in the SARS-CoV-2 pandemic

Inhibition of the Nicotinic Acetylcholine Receptors by Cobra Venom α-Neurotoxins: Is There a Perspective in Lung Cancer Treatment?

Nicotine exerts its oncogenic effects through the binding to nicotinic acetylcholine receptors (nAChRs) and the activation of downstream pathways that block apoptosis and promote neo-angiogenesis. The nAChRs of the α7 subtype are present on a wide variety of cancer cells and their inhibition by cobra venom neurotoxins has been proposed in several articles and reviews as a potential innovative lung cancer therapy. However, since part of the published results was recently retracted, we believe that the antitumoral activity of cobra venom neurotoxins needs to be independently re-evaluated

Trait-based model development to support breeding programs : A case study for salt tolerance and rice

Eco-physiological models are increasingly used to analyze G 7 E 7 M interactions to support breeding programs via the design of ideotypes for specific contexts. However, available crop models are only partly suitable for this purpose, since they often lack clear relationships between parameters and traits breeders are working on. Taking salt stress tolerance and rice as a case study, we propose a paradigm shift towards the building of ideotyping-specific models explicitly around traits involved in breeding programs. Salt tolerance is a complex trait relying on different physiological processes that can be alternatively selected to improve the overall crop tolerance. We developed a new model explicitly accounting for these traits and we evaluated its performance using data from growth chamber experiments (e.g., R2 ranged from 0.74 to 0.94 for the biomass of different plant organs). Using the model, we were able to show how an increase in the overall tolerance can derive from completely different physiological mechanisms according to soil/water salinity dynamics. The study demonstrated that a trait-based approach can increase the usefulness of mathematical models for supporting breeding programs