Modeling Heterogeneous Materials via Two-Point Correlation Functions: II. Algorithmic Details and Applications

In the first part of this series of two papers, we proposed a theoretical formalism that enables one to model and categorize heterogeneous materials (media) via two-point correlation functions S2 and introduced an efficient heterogeneous-medium (re)construction algorithm called the "lattice-point" algorithm. Here we discuss the algorithmic details of the lattice-point procedure and an algorithm modification using surface optimization to further speed up the (re)construction process. The importance of the error tolerance, which indicates to what accuracy the media are (re)constructed, is also emphasized and discussed. We apply the algorithm to generate three-dimensional digitized realizations of a Fontainebleau sandstone and a boron carbide/aluminum composite from the two- dimensional tomographic images of their slices through the materials. To ascertain whether the information contained in S2 is sufficient to capture the salient structural features, we compute the two-point cluster functions of the media, which are superior signatures of the micro-structure because they incorporate the connectedness information. We also study the reconstruction of a binary laser-speckle pattern in two dimensions, in which the algorithm fails to reproduce the pattern accurately. We conclude that in general reconstructions using S2 only work well for heterogeneous materials with single-scale structures. However, two-point information via S2 is not sufficient to accurately model multi-scale media. Moreover, we construct realizations of hypothetical materials with desired structural characteristics obtained by manipulating their two-point correlation functions.Comment: 35 pages, 19 figure

Characterisation of Vernaccia Nera (Vitis vinifera L.) grapes and wine

Vernaccia Nera (VN) is a minor Italian red grape cultivar whose oenological properties have not been investigated yet. Traditional winemaking procedures with VN can include grape drying and even triple sequential fermentations, but a rational vinification approach should be based on the grape composition. Since a comprehensive characterisation of the VN grape is still missing, the ripening of VN grapes was monitored by evaluating flavour compounds, proanthocyanidins and anthocyanins. The grapes were used to produce red wine whose chemical composition and sensory properties were assessed. Ripe VN grapes contained high amounts of extractable anthocyanins (0.88 g/kg). The most abundant anthocyanin was malvidin (56.6%), and high relative amounts of cumarate forms (11.3%) were also found. The grape skin showed a high concentration of proanthocyanidins (2 g/kg), whose degree of polymerisation was low (10.3). Epigallocatechin accounted for up to 39% of the flavan-3-ol units in the skin. Flavour compounds in the grapes included glycosylated norisoprenoids (mainly 3-oxo-alpha-ionol and vomifoliolo) and benzenoids. The VN red wine showed a high concentration of anthocyanins, but the level of proanthocyanidins (0.93 g/L) was lower than expected. The spicy flavours were the notes mostly recognised in the sensory evaluation. Our data highlight the VN grape as suitable for the production of ready-to-drink or shortly aged red wine due to its high acidity and low astringency

Fluctuations in Stationary non Equilibrium States

In this paper we formulate a dynamical fluctuation theory for stationary non equilibrium states (SNS) which covers situations in a nonlinear hydrodynamic regime and is verified explicitly in stochastic models of interacting particles. In our theory a crucial role is played by the time reversed dynamics. Our results include the modification of the Onsager-Machlup theory in the SNS, a general Hamilton-Jacobi equation for the macroscopic entropy and a non equilibrium, non linear fluctuation dissipation relation valid for a wide class of systems

Tracing CP-violation in Lepton Flavor Violating Muon Decays

Although the Lepton Flavor Violating (LFV) decay $\mu^+\to e^+ \gamma$ is forbidden in the Standard Model (SM), it can take place within various theories beyond the SM. If the branching ratio of this decay saturates its present bound [{\it i.e.,} Br$(\mu^+ \to e^+\gamma)\sim 10^{-11}$], the forthcoming experiments can measure the branching ratio with high precision and consequently yield information on the sources of LFV. In this letter, we show that for polarized $\mu^+$, by studying the angular distribution of the transversely polarized positron and linearly polarized photon we can derive information on the CP-violating sources beyond those in the SM. We also study the angular distribution of the final particles in the decay $\mu^+\to e^+_1 e^- e^+_2$ where $e^+_1$ is defined to be the more energetic positron. We show that transversely polarized $e_1^+$ can provide information on a certain combination of the CP-violating phases of the underlying theory which would be lost by averaging over the spin of $e^+_1$.Comment: 6 pages, 2 figure

Stochastic interacting particle systems out of equilibrium

This paper provides an introduction to some stochastic models of lattice gases out of equilibrium and a discussion of results of various kinds obtained in recent years. Although these models are different in their microscopic features, a unified picture is emerging at the macroscopic level, applicable, in our view, to real phenomena where diffusion is the dominating physical mechanism. We rely mainly on an approach developed by the authors based on the study of dynamical large fluctuations in stationary states of open systems. The outcome of this approach is a theory connecting the non equilibrium thermodynamics to the transport coefficients via a variational principle. This leads ultimately to a functional derivative equation of Hamilton-Jacobi type for the non equilibrium free energy in which local thermodynamic variables are the independent arguments. In the first part of the paper we give a detailed introduction to the microscopic dynamics considered, while the second part, devoted to the macroscopic properties, illustrates many consequences of the Hamilton-Jacobi equation. In both parts several novelties are included.Comment: 36 page

Mucopolysaccharidosis type II: preliminary data on glycosaminoglycan levels and structure in mice at baseline and after 6 weeks treatment with ERT

Mucopolysaccharidosis type II is a lysosomal storage disease due to the deficit of the enzyme iduronate 2-sulfatase (IDS) and to the consequent accumulation of heparan- (HS) and dermatan-sulfate (DS), with multi-organ involvement. In this study we characterized glycosaminoglycan (GAG) levels and structure in the brain and liver of the Ids knock-out mouse model, at 12 weeks of age and after 6 weeks treatment with human IDS (hIDS) enzyme, by using the capillary electrophoresis-laser induced fluorescence (CE-LIF) technique. As expected, Ids-ko mice showed a heavy accumulation of HS, about 15 times higher than wild-type (wt) in the brain and up to 240 times in the liver. The overall HS charge density rose by 1.5 times only in the liver, but the sulfation pattern changed in both organs. We also observed an increased chondroitin-sulfate (CS)+DS levels of about 2 times in the brain and 5 times in the liver, but an increased CS/DS ratio of about 22 times only in the liver. On the contrary, the hyaluronic acid (HA) levels did not change in both organs. We also conducted the same analysis in Ids-ko mice treated with 1 mg/kg of hIDS, once a week. As expected, we observed in the liver a huge reduction of HS (20 times vs untreated mice) and also of CS+DS and CS/DS. Instead, we did not observe a reduction of the different GAGs in the brain, confirming the enzyme inability to cross BBB. In this district a slight increase of CS/DS ratio, CS+DS and HA levels, and an about 40% increase of HS level, vs untreated ko mice, was observed. On the opposite, the overall HS charge density is decreased 2.5X vs untreated ko and wt mice. This preliminary data underline how by using a more sensitive technique of analysis, a clear separation of the GAGs pattern between wt and Ids-ko mice can be observed. This results particularly important for the brain, where application of common biochemical techniques detects very low GAG levels in both animal types, thus limiting the use of GAG analysis as possible biomarker of therapeutic efficacy in the brain district. The application of CE-LIF analysis is therefore proposed for a detailed evaluation of GAG pattern for potential monitoring of therapeutic efficacy

AB0413 HIGH-RESOLUTION COMPUTED TOMOGRAPHY FOR THE SCREENING, RE-SCREENING AND FOLLOW-UP OF SYSTEMIC SCLEROSIS RELATED INTERSTITIAL LUNG DISEASE: RESULTS OF A EUSTAR-SCTC SURVEY

Background:High-resolution computed tomography (HRCT) is the gold standard diagnostic test for Interstitial lung disease (ILD), a significant cause of morbidity and mortality in systemic sclerosis (SSc). Different algorithms have been proposed for the screening of SSc-ILD, including the use of pulmonary function tests (Forced Vital Capacity - FVC, Lung Diffusion of Carbone Monoxyde - DLCO). A prior survey reported that 50-66% of general rheumatologists and SSc experts ordered HRCT for ILD screening in newly diagnosed SSc patients (1).Objectives:Given the recent availability of on-label treatment for SSc-ILD (2), the publication of consensus recommendations for the identification of SSc-ILD (3) and recent awareness programs for the use of HRCT to detect SSc-ILD, we aimed to re-evaluate the use of HRCT for screening, re-screening and follow-up of SSc-ILD.Methods:An invitation was sent to the European Scleroderma Trials and Research (EUSTAR) and Scleroderma Clinical Trials Consortium (SCTC) members, also advertised through social media. Answers were recorded between Nov 25th and Dec 31st 2020. Questions were asked on the use of chest HRCT at baseline, the re-screening of patients with a negative baseline HRCT and the follow-up of HRCT positive SSc-ILD patients. When HRCT was not routinely requested, additional details were collected about the parameters guiding its use. The results of the survey were tested for association with geographical origin, medical specialty, working environment, SSc referral institute and scientific group membership of the responders, using Chi-squared test.Results:205/630 (32.5%) physicians replied to the survey. Participants were widely distributed in terms of geographical origin (130 Europe, 23 Asia, 23 North America, 31 other continents), medical specialty (156 rheumatology, 21 internal medicine, 14 clinical immunology, 14 other), working environment (176 University Hospital, 12 community hospital, 17 other), SSc dedicated clinic (179 referral and 26 non-referral) and scientific group membership (98 EUSTAR, 42 SCTC, 42 EUSTAR and SCTC, 23 not declared).At SSc diagnosis, 95.7% of responders would perform HRCT: 66.7% as routine screening for ILD (67,4% of SSc referral and 62% for non-referral physicians) and 29% for diagnostic purposes (among the latter, if crackles on auscultation – 92.5%, FVC<80% predicted - 86.6%, FVC±DLCO relative decline reaching the current definition of ILD progression, 86.6% or dyspnea at rest/exercise - 85.1/83.3%).During follow-up, 78.8% of responders would repeat an HRCT in baseline negative cases: 20.3% as a yearly routine screening and 64.5% for diagnostic aims (decision on the latter group was more frequently driven by FVC±DLCO relative decline indicative of ILD progression– 90.6%, new onset or worsening of dyspnoea at rest/exercise – 80.5/86.6%, new onset or worsening of lung crackles on auscultation – 82.6%).Finally, 94.5% of responders would repeat a chest HRCT after SSc-ILD diagnosis: 36.8% as a yearly routine and 56.7% according to clinical evaluation (driven by new FVC±DLCO relative decline based ILD progression – 90.8%, new onset or worsening of dyspnoea at rest/exercise – 83.2/81.7%; 5.2% to evaluate treatment effects). We found no difference in the distribution of answers among groups.Conclusion:The use of baseline HRCT for the screening of SSc-ILD has slightly increased in non-referral and remained stable in referral centers compared to previous surveys, indicating that the implementation of guidelines might be successful and awareness programs should be continued. In addition, we provide new data on use of HRCT in re-screening and follow-up. The development of validated algorithms to further support the appropriate application of HRCT at follow-up is highly needed.References:[1]Bernstein EJ et al. Arthritis Rheumatol. 2018 Jun;70(6):971-972.[2]Distler O et al. N Engl J Med. 2019 Jun 27;380(26):2518-2528.[3]Hoffmann-Vold AM et al. The Lancet Rheumatology, Volume 2, Issue 2, e71 - e83.Disclosure of Interests:Cosimo Bruni Speakers bureau: Actelion, Consultant of: Eli Lilly, Grant/research support from: Foundation for Research in Rheumatology (FOREUM), Gruppo Italiano Lotta alla Sclerodermia (GILS), Fondazione Italiana per la Ricerca sull'Artrite (FIRA), New Horizon Fellowship, European Sclerodermia Trial and Reserach (EUSTAR) Group., Lorinda Chung Consultant of: Boehringer Ingelheim, Eicos, Mitsubishi Tanabe, Reata., Anna-Maria Hoffmann-Vold Consultant of: Actelion, ARXX therapeutics, Bayer, Boehringer-Ingelheim, Medscape, MSD, Lilly, Roche, Shervin Assassi Speakers bureau: Integrity Continuing Education, Consultant of: Boehringer Ingelheim, Novartis, and Corbus, Armando Gabrielli: None declared, Dinesh Khanna Consultant of: Acceleron, Actelion, Abbvie, Amgen, Bayer, Boehringer Ingelheim, CSL Behring, Corbus, Gilead, Galapagos, Genentech/Roche, GSK, Horizon, Merck, Mitsubishi Tanabe Pharma, Sanofi-Aventis, and United Therapeutics Leadership, Grant/research support from: NIH, Immune Tolerance Network, Bayer, BMS, Horizon, Pfizer, Employee of: Equity position – Chief Medical Officer, Eicos Sciences, Inc., Elana Bernstein Consultant of: Boehringer Ingelheim, Oliver Distler Consultant of: Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB., Grant/research support from: Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued "mir-29 for the treatment of systemic sclerosis" (US8247389, EP2331143)

Riesgo de caries dental en pacientes de tres a seis años que acuden a la clínica de la de la Universidad Nacional Federico Villarreal

El objetivo del presente estudio fue determinar el riesgo de caries dental que presentan los pacientes de tres a seis años que acudieron a la clínica de la Universidad Nacional Federico Villarreal en el año 2011. La muestra fue de 50 niños de ambos sexos que cumplieron con los criterios de inclusión y exclusión, a quienes se les realizó una encuesta y una evaluación del índice de higiene oral para determinar la presencia y nivel de riesgo de caries dental. Los resultados obtenidos fueron que en los factores de riesgo de caries dental estudiados en la presente investigación están presentes indistintamente la edad y el sexo. El factor de riesgo más prevalente es el cepillado dental con 21 casos, seguido del factor visita al odontólogo con 19 casos. El riesgo de caries dental más prevalente es el “Riesgo Bajo” con un 40.8%, seguido de 37.6% con un “Riesgo Mediano” y 21.8% presentan “Riesgo Alto”. Al relacionar los valores se determinó que no hay diferencias significativas de los factores de riesgo de caries dental en relación al sexo, encontrándose diferencias altamente significativas entre los niveles de caries dental y la presencia de los factores de riesgo.Palabras claves: caries dental, riesgo, factores de riesg