Enforcing ensemble averages in molecular dynamics simulations using the Maximum Entropy principle

Molecular dynamics (MD) simulations in explicit solvent are nowadays a fundamental tool used to complement experimental investigations in biomolecular modeling. Typical molecular dynamics simulations are usually limited to the microseconds timescale, although milliseconds timescales can be achieved with ad-hoc machines. To overcome timescale limitations, over the years several enhanced sampling techniques have been developed, allowing to sample events that would require a much longer time in order to spontaneously happen. Simulations length is only one of the two factors contributing to simulations accuracy. The second important factor is the ability of the employed potential energy function, also called force field, to correctly describe the physics of the simulated system. The continuous refinement of enhanced sampling techniques, together with the constant growth of computing power, made the force field the major responsible of simulations inaccuracy. It is then necessary to always validate molecular simulations against experiments when possible. The usual procedure consists in performing a simulation and computing some observable for which an experimental value has been already measured. If the calculated and experimental values are compatible, the simulation can be trusted and other observables can be estimated in order to make genuine predictions. If the discrepancy between calculated and experimental values is significant, one is forced to make a step back and perform a new simulation with a refined force field. For instance, current force fields still exhibit visible limitations in the study of protein-protein interactions, in the structural characterization of protein unfolded states, in the simulation of the conformational dynamics of unstructured RNAs, and in the blind prediction of RNA structural motifs. Force fields improvement is a very challenging task with many groups involved in this “undertaking”. In fact, many correlated parameters should be adjusted, and modifications of one of them could easily lead to unpredictable effects on all the others. Furthermore, it is not guaranteed that the employed potential energy functional form is sufficient to describe the real energy function of the system. As a consequence, an emerging strategy is to restrain the simulations in order to enforce the agreement with experimental data. It must be noticed that experimental knowledge is usually already encoded in the simulation of complex systems (e.g., a short simulation starting from an experimental structure will then be biased toward it). If properly combined with simulations, experiments can be a valuable alternative to quantum chemistry based force-field refinement. Moreover, it must be noticed that usually quantum chemistry calculations are performed on short fragments while experiments are usually performed on much longer molecules. Particular care should be taken when interpreting bulk experiments that measure averages over a large number of copies of the same molecule. These experiments are valuable in the characterization of dynamical molecules, where heterogeneous structures might be mixed and contribute with different weights to the experimental observation. In such cases, a proper combination of them with molecular simulations can allow to construct a high-resolution picture of molecular structure and dynamics

Using the maximum entropy principle to combine simulations and solution experiments

Molecular dynamics (MD) simulations allow the investigation of the structural dynamics of biomolecular systems with unrivaled time and space resolution. However, in order to compensate for the inaccuracies of the utilized empirical force fields, it is becoming common to integrate MD simulations with experimental data obtained from ensemble measurements. We review here the approaches that can be used to combine MD and experiment under the guidance of the maximum entropy principle. We mostly focus on methods based on Lagrangian multipliers, either implemented as reweighting of existing simulations or through an on-the-fly optimization. We discuss how errors in the experimental data can be modeled and accounted for. Finally, we use simple model systems to illustrate the typical difficulties arising when applying these methods

Insurance Fraud Detection: A Statistically-Validated Network Approach

Fraud is a social phenomenon, and fraudsters oftencollaborate with other fraudsters, taking on differentroles. The challenge for insurance companies is toimplement claim assessment and improve frauddetection accuracy. We developed an investigativesystem based on bipartite networks, highlighting therelationships between subjects and accidents or vehi-cles and accidents. We formalize filtering rules throughprobability models and test specific methods to assessthe existence of communities in extensive networksand propose new alert metrics for suspicious struc-tures. We apply the methodology to a real database—the Italian Antifraud Integrated Archive—and compare the results to out‐of‐sample fraud scams underinvestigation by the judicial authoritie

Shipping and Air Quality in Italian Port Cities: State-of-the-Art Analysis of Available Results of Estimated Impacts

Populated coastal areas are exposed to emissions from harbour-related activities (ship traffic, loading/unloading, and internal vehicular traffic), posing public health issues and environmental pressures on climate. Due to the strategic geographical position of Italy and the high number of ports along coastlines, an increasing concern about maritime emissions from Italian harbours has been made explicit in the EU and IMO (International Maritime Organization, London, UK) agenda, also supporting the inclusion in a potential Mediterranean emission control area (MedECA). This work reviews the main available outcomes concerning shipping (and harbours') contributions to local air quality, particularly in terms of concentration of particulate matter (PM) and gaseous pollutants (mainly nitrogen and sulphur oxides), in the main Italian hubs. Maritime emissions from literature and disaggregated emission inventories are discussed. Furthermore, estimated impacts to air quality, obtained with dispersion and receptor modeling approaches, which are the most commonly applied methodologies, are discussed. Results show a certain variability that suggests the necessity of harmonization among methods and input data in order to compare results. The analysis gives a picture of the effects of this pollution source, which could be useful for implementing effective mitigation strategies at a national level

Multi-Year Concentrations, Health Risk, and Source Identification, of Air Toxics in the Venice Lagoon

This work presents and discusses the results of multi-year measurements of air toxics concentrations from different sites of Venice Lagoon. The aim of the study is the characterization of the air quality of the area, in terms of PM10, PM10-bound metals, and polycyclic aromatic hydrocarbons (PAHs) concentrations, even with the individuation of the related inhalation risk and the identification of the main contaminants' sources. The study moreover provides an important multi-years trend of chemical characterization of the Venice Lagoon. Sampling for PM10 and its metal content was carried out between 2010 and 2015, using low volume sequential aerosol samplers; V, Cr, Fe, Co, Ni, Cu, Zn, As, Mo, Cd, Sb, Tl, and Pb were measured by ICP-MS. Samples for PAHs concentration in gas and particle phases were collected from 2010 to 2014, using a high-volume air sampler that allows to sample both phases simultaneously. Samples for PAHs determinations were analyzed by GC-HRMS. Concentrations of air toxics have been studied with the use of enrichment factor, the coefficient of divergence, and the Mann-Kendal test, to individuate eventual local divergences, seasonal and other temporal trends. The inhalation risk assessment has been achieved by the calculation of the cumulative incremental carcinogenic risk for all the air toxics analyzed. The sources' identification and impact evaluation have been carried out using the atmospheric vanadium concentration, to calculate the primary contribution of ship traffic to PM10, the Positive Matrix Factorization, and the Diagnostic Ratios, with the aim of evaluating the impact of construction activities of M.o.S.E, (Modulo Sperimentale Elettromeccanico-Electromechanical Experimental Module) as well as of ship traffic and other possible air toxics' sources. Temporal trends indicate a slight decrease of PAHs and PM10 and of its content of Pb, Zn, Sb. Sharp increases of As and Cd during 2014 and 2015 may be due to local sources like emissions from the construction yard, ship, and road traffic. The cumulative incremental carcinogenic risk was below the unconditionally acceptable risk; Co and As are the most important contributors among metals, followed by Cd and Ni while the PAH congeners that most contribute to the carcinogenic risk were benzo(a)pyrene and dibenzo(A,H)anthracene

Use of wastes from the peanut industry in the manufacture of building materials

Most of the national peanut production, estimated at 900,000 tons per year, is processed in several cities in the central area of Argentina. The third part of this amount corresponds to the shells, which are separated in the peanut selection and processing plants. In this work, the possibility of using peanut shells as raw material for the manufacture of ceramic materials for the civil construction industry is studied. There are precedents on the use of biomass residues in different building blocks, mainly with the aim of generating lightweight ceramics. With this objective, ceramic pieces were obtained from green bodies manufactured with mixtures of commercial clay and different percentages of ground and dry residue. After a drying period, the samples were heat treated following curves similar to those used in the ceramic industry. The raw material used, clay and peanut shells, were characterized with different techniques, such as XRD, SEM and DTA-TGA. The DTA-TGA analysis shows that the organic material added is burned in a wide temperature range, between 300 °C and 550 °C. Thus, the sintering process of the bricks is performed without cracking or shattering. This test also shows that after the heat treatment, the waste material eventually incorporated into bricks (ashes) is less than 3%. The obtained products have good physical and mechanical properties, with acceptable values of porosity, modulus of rupture, permanent volumetric variation and weight loss on ignition.Fil: Quaranta, Nancy Esther. Universidad Tecnológica Nacional. Facultad Regional San Nicolás; ArgentinaFil: Caligaris, Marta Graciela. Universidad Tecnológica Nacional. Facultad Regional San Nicolás; ArgentinaFil: Pelozo, Gisela Guadalupe. Universidad Tecnológica Nacional. Facultad Regional San Nicolás; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cesari, Andrea. Universidad Tecnológica Nacional. Facultad Regional San Nicolás; ArgentinaFil: Cristobal, Adrian Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; Argentin

Lipid Peroxidation and Depressed Mood in Community-Dwelling Older Men and Women

It has been hypothesized that cellular damage caused by oxidative stress is associated with late-life depression but\ud epidemiological evidence is limited. In the present study we evaluated the association between urinary 8-iso-prostaglandin\ud F2a (8-iso-PGF2a), a biomarker of lipid peroxidation, and depressed mood in a large sample of community-dwelling older\ud adults. Participants were selected from the Health, Aging and Body Composition study, a community-based longitudinal\ud study of older persons (aged 70–79 years). The present analyses was based on a subsample of 1027 men and 948 women\ud free of mobility disability. Urinary concentration of 8-iso-PGF2a was measured by radioimmunoassay methods and adjusted\ud for urinary creatinine. Depressed mood was defined as a score greater than 5 on the 15-item Geriatric Depression Scale and/\ud or use of antidepressant medications. Depressed mood was present in 3.0% of men and 5.5% of women. Depressed men\ud presented higher urinary concentrations of 8-iso-PGF2a than non-depressed men even after adjustment for multiple\ud sociodemographic, lifestyle and health factors (p=0.03, Cohen’s d = 0.30). This association was not present in women\ud (depressed status-by-sex interaction p = 0.04). Our study showed that oxidative damage may be linked to depression in\ud older men from a large sample of the general population. Further studies are needed to explore whether the modulation of\ud oxidative stress may break down the link between late-life depression and its deleterious health consequences

Traditional farmers’ varieties: a valuable source of genetic variability for biofortification programs

Several studies underlined the superiority from a nutritional point of view of ancient varieties. In the last years the interest for landraces has been growing, for this reason preservation and valorisation of these genetic sources is very important. In particular these varieties are source of precious genetic variability interesting from a scientific point of view to preserve biodiversity but also for biofortification programs aimed to support small rural communities, where the particular maize germplasm has been developed. In this work we characterized from the nutritional point of view 13 ancient Italian varieties and one coming from Spain (Millo Corvo). In this pre-breeding work we demonstrate the nutritional superiority of ancient varieties if compared with modern hybrids. In particular Spinato di Gandino is the best variety for milling properties and for oil, protein, and total phosphorus content; Storo is the best variety for calorific value and for carotenoids and free phosphorus content. Using these varieties in the next future we will start a bio-fortification program aimed to obtain new populations with improved yields and high nutritional value

Synthesis of functionalized iron N-heterocyclic carbene complexes and their potential application as flame behavior modifier in cross linked epoxy resins

The design of new flame retardants (FR) that avoid the use of halogen and phosphorus additives is challenging and urgent. Herein we report on the synthesis of bis-amino functionalized N-heterocyclic carbene cyclopentadienone iron complexes aimed at promoting the production of iron containing epoxy resins. Iron complexes are successfully employed to obtain high Tg thermosets with as low as 5% hardener content. Moreover the obtained resins display an impressive charring ability that paves the way to the application of such systems for material with improved flame behavior