STRATIGRAPHY, PALEOGEOGRAPHY AND GENETIC MODEL OF LATE CARNIAN CARBONATE BRECCIAS (CASTRO FORMATION, LOMBARDY, ITALY)

The stratigraphic and paleogeographic analysis of the Carnian-Norian boundary succession in central Lombardy allows the recognition of a new unit, the Castro Formation. This unit, 100-250 m thick, is represented by carbonatic intraformational breccias and associated limestones. Two lithozones have been recognized in the Castro Fm.: the lower one, heteropic with the S.Giovanni Bianco Fm., with dark dolomitic limestones and breccias intercalations, and the upper lithozone, massive, with amalgamated calcareous breccias. Microfacies, recrystallized and often tectonized, consist of mudstones, wackestones and fine packstones, locally rich in ostracods. Geochemical analyses show differences between the Castro Fm. and the overlying and underlying units, possibly because of early diagenetic meteoric imprint. The Castro Fm. depositional setting is represented by coastal ephemeral lakes with periodic emersions and erosional, tectonically controlled phenomena in a monsoonal regime

QM/MM MD and Free Energy Simulations of G9a-Like Protein (GLP) and Its Mutants: Understanding the Factors that Determine the Product Specificity

Certain lysine residues on histone tails could be methylated by protein lysine methyltransferases (PKMTs) using S-adenosyl-L-methionine (AdoMet) as the methyl donor. Since the methylation states of the target lysines play a fundamental role in the regulation of chromatin structure and gene expression, it is important to study the property of PKMTs that allows a specific number of methyl groups (one, two or three) to be added (termed as product specificity). It has been shown that the product specificity of PKMTs may be controlled in part by the existence of specific residues at the active site. One of the best examples is a Phe/Tyr switch found in many PKMTs. Here quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) and free energy simulations are performed on wild type G9a-like protein (GLP) and its F1209Y and Y1124F mutants for understanding the energetic origin of the product specificity and the reasons for the change of product specificity as a result of single-residue mutations at the Phe/Tyr switch as well as other positions. The free energy barriers of the methyl transfer processes calculated from our simulations are consistent with experimental data, supporting the suggestion that the relative free energy barriers may determine, at least in part, the product specificity of PKMTs. The changes of the free energy barriers as a result of the mutations are also discussed based on the structural information obtained from the simulations. The results suggest that the space and active-site interactions around the ε-amino group of the target lysine available for methyl addition appear to among the key structural factors in controlling the product specificity and activity of PKMTs

A Comparative Study on the Nonlinear Interaction Between a Focusing Wave and Cylinder Using State-of-the-art Solvers: Part A

This paper presents ISOPE’s 2020 comparative study on the interaction between focused waves and a fixed cylinder. The paper discusses the qualitative and quantitative comparisons between 20 different numerical solvers from various universities across the world for a fixed cylinder. The moving cylinder cases are reported in a companion paper as part B (Agarwal, Saincher, et al., 2021). The numerical solvers presented in this paper are the recent state of the art in the field, mostly developed in-house by various academic institutes. The majority of the participants used hybrid modeling (i.e., a combination of potential flow and Navier–Stokes solvers). The qualitative comparisons based on the wave probe and pressure probe time histories and spectral components between laminar, turbulent, and potential flow solvers are presented in this paper. Furthermore, the quantitative error analyses based on the overall relative error in peak and phase shifts in the wave probe and pressure probe of all the 20 different solvers are reported. The quantitative errors with respect to different spectral component energy levels (i.e., in primary, sub-, and superharmonic regions) capturing capability are reported. Thus, the paper discusses the maximum, minimum, and median relative errors present in recent solvers as regards application to industrial problems rather than attempting to find the best solver. Furthermore, recommendations are drawn based on the analysis

Insights from Modeling the 3D Structure of New Delhi Metallo-β-Lactamse and Its Binding Interactions with Antibiotic Drugs

New Delhi metallo-beta-lactamase (NDM-1) is an enzyme that makes bacteria resistant to a broad range of beta-lactam antibiotic drugs. This is because it can inactivate most beta-lactam antibiotic drugs by hydrolyzing them. For in-depth understanding of the hydrolysis mechanism, the three-dimensional structure of NDM-1 was developed. With such a structural frame, two enzyme-ligand complexes were derived by respectively docking Imipenem and Meropenem (two typical beta-lactam antibiotic drugs) to the NDM-1 receptor. It was revealed from the NDM-1/Imipenem complex that the antibiotic drug was hydrolyzed while sitting in a binding pocket of NDM-1 formed by nine residues. And for the case of NDM-1/Meropenem complex, the antibiotic drug was hydrolyzed in a binding pocket formed by twelve residues. All these constituent residues of the two binding pockets were explicitly defined and graphically labeled. It is anticipated that the findings reported here may provide useful insights for developing new antibiotic drugs to overcome the resistance problem

Single-well reactive tracer test and stable isotope analysis for determination of microbial activity in a fast hydrocarbon-contaminated aquifer.

Single-well reactive tracer tests, such as the push-pull test are useful tools for characterising in-situ bioattenuation processes in contaminated aquifers. However, the analytical models that are used to interpret push-pull data may be over-simplified, and potentially overlook important processes responsible for the frequent discrepancy between predicted and observed results obtained from push-pull tests. In this study, the limitations underlying the push-pull test methodology were investigated and were supported with results from a push-pull test conducted in a sulphate-reducing aquifer contaminated by crude oil. Poor (<7%) mass recovery was achieved when the push-pull test was performed in a fast-flowing aquifer, preventing a quantifiable reaction rate to be determined. Breakthrough curve data were unexplainable using simplified analytical models, but exhibited trends analogous with tests conducted by others, when >20% mass recoveries were achieved. Push-pull test data collected from sulphate-reducing aquifers indicate that the assumption of a well-mixed batch reactor system is incorrect and that reaction rates obtained from push-pull tests in such systems may be affected by the extraction regime implemented. Evidence of microbial respiration of the reactive tracer was provided by stable sulphur isotope analysis, from which an isotope fractionation factor of +9.9 +/- 8.1%. was estimated. The stable isotope data support the argument that reaction rates calculated using push-pull tests are not uniformly distributed in space and time and are likely to be influenced by heterogeneities in the flow field. (C) 2003 Elsevier Ltd. All rights reserved

High Order Scheme for Mixed Formulation of Problems with Moving Internal Boundaries

International audienc

High Order Scheme for Mixed Formulation of Problems with Moving Internal Boundaries

International audienc