Combining Different Docking Engines and Consensus Strategies to Design and Validate Optimized Virtual Screening Protocols for the SARS-CoV-2 3CL Protease

The 3CL-Protease appears to be a very promising medicinal target to develop anti-SARS-CoV-2 agents. The availability of resolved structures allows structure-based computational approaches to be carried out even though the lack of known inhibitors prevents a proper validation of the performed simulations. The innovative idea of the study is to exploit known inhibitors of SARS-CoV 3CL-Pro as a training set to perform and validate multiple virtual screening campaigns. Docking simulations using four different programs (Fred, Glide, LiGen, and PLANTS) were performed investigating the role of both multiple binding modes (by binding space) and multiple isomers/states (by developing the corresponding isomeric space). The computed docking scores were used to develop consensus models, which allow an in-depth comparison of the resulting performances. On average, the reached performances revealed the different sensitivity to isomeric differences and multiple binding modes between the four docking engines. In detail, Glide and LiGen are the tools that best benefit from isomeric and binding space, respectively, while Fred is the most insensitive program. The obtained results emphasize the fruitful role of combining various docking tools to optimize the predictive performances. Taken together, the performed simulations allowed the rational development of highly performing virtual screening workflows, which could be further optimized by considering different 3CL-Pro structures and, more importantly, by including true SARS-CoV-2 3CL-Pro inhibitors (as learning set) when available.     

Enrichment from activated sludges of aerobic mixed cultures capable to degrade vinyl chloride (VC) as the sole carbon source

Two microbial cultures able to degrade high concentrations of VC as the sole carbon source have been obtained by enrichment from activated sludge. The cultures began consuming VC (0.02 mmol l(-1)) only after a long initial acclimation period (1-2 months). After then the concentration of VC was gradually increased (from 0.02 to 0.8 mmol l(-1)) and the cultures were able to maintain VC degrading ability for long time (over 500 days). VC-degrading biomass in the two cultures was characterized by low specific maximum growth rates (0.19-0.21 d(-1)) compared to heterotrophic organisms typically present in activated sludge processes. Monod half-saturation constant was rather low (0.7-1.6 mg VC l(-1)) indicating that it is possible to effectively remove VC to low residual concentrations. The cultures were highly sensitive to even short periods of VC lack (with quick decrease of VC degradation rates) whereas they were not to sudden load increases (up to 3.4 mmol l(-1)). After being cultured with only ethene as the sole carbon and energy source, the cultures kept the ability of degrading VC. Possibility of maintaining the mixed cultures on non-toxic ethene, without loosing VC degradation ability, is very promising for bioaugmentation treatments.     

Shape controlled interpolatory ternary subdivision

Ternary subdivision schemes compare favorably with their binary analogues because they are able to generate limit functions with the same (or higher) smoothness but smaller support.In this work we consider the two issues of local tension control and conics reproduction in univariate interpolating ternary refinements. We show that both these features can be included in a unique interpolating 4-point subdivision method by means of non-stationary insertion rules that do not affect the improved smoothness and locality of ternary schemes. This is realized by exploiting local shape parameters associated with the initial polyline edges.     

A general framework for the construction of piecewise-polynomial local interpolants of minimum degree

In this paper we consider the problem of designing piecewise polynomial local interpolants of non-uniformly spaced data. We provide a constructive approach that, for any assigned degree of polynomial reproduction, continuity order, and support width, allows for generating the fundamental spline functions of minimum degree having the desired properties. Finally, the proposed construction is extended to handle open sets of data and to the case of multiple knots.     

Estimation of measurement uncertainty for the determination of aflatoxin M1 in milk using immunoaffinity clean-up procedures

A measurement uncertainty estimated for aflatoxin M₁ determination in milk sample has been calculated using data generated from analytical method validation studies. The protocol adopted is described in detail in document LGC/VAM/1998/088. The uncertainty budget was based on precision, trueness and ruggedness data. The individual contributions are described in detail. The expanded uncertainty for aflatoxin M ₁ at a concentration of 20 ng L⁻¹ was estimated as 2.81 ng L⁻¹. This was calculated using a coverage factor of two which gives a level of confidence of approximately 95%. Presented at AOAC Europe / Eurachem Symposium March 2005, Brussels, Belgium     

Non-uniform interpolatory curve subdivision with edge parameters built upon compactly supported fundamental splines

In this paper we present a family of Non-Uniform Local Interpolatory (NULI) subdivision schemes, derived from compactly supported interpolatory fundamental splines with non-uniform knots (NULIFS). For this spline family, the knot-partition is defined by a sequence of break points and by one additional knot, arbitrarily placed along each knot-interval. The resulting refinement algorithms are linear and turn out to contain a set of edge parameters that, when fixed to a value in the range [0,1], allow us to achieve special shape features by simply moving each auxiliary knot between the break points. Among all the members of this new family of schemes, we will then especially analyze the NULI 4-point refinement. This subdivision scheme has all the fundamental features of the quadratic fundamental spline basis it is originated from, namely compact support, C ¹ smoothness, second order polynomials reproduction and approximation order 3. In addition the NULI 4-point subdivision algorithm has the possibility of setting consecutive edge parameters to simulate double and triple knots—that are not considered by the authors of the corresponding spline basis—thus allowing for limit curves with crease vertices, without using an ad hoc mask. Numerical examples and comparisons with other methods will be given to the aim of illustrating the performance of the NULI 4-point scheme in the case of highly non-uniform initial data.     

A smoothness criterion for monotonicity-preserving subdivision

In this paper we study subdivision schemes that both interpolate and preserve the monotonicity of the input data, and we derive a simple ratio condition that guarantees the continuous differentiability of the limit function. We then show that the condition holds for both a scheme of Kuijt and van Damme, based on rational functions, and a scheme of Sabin and Dodgson, based on square roots.     

Estimation of uncertainty for the determination of mercury in food by CVAAS

This paper is aimed at reporting a full validation of a Cold Vapour Atomic Absorption Spectrometry (CVAAS) method for mercury determination in fishery products. Method precision, trueness, limit of detection and limit of quantification are evaluated. The uncertainty of measurement is estimated following the bottom-up approach in conjunction with the validation data as suggested for complex analysis. The precision is evaluated using a pooled relative standard deviation and the recovery is added to the measurement uncertainty budget. Uncertainties of weight of sample, dilution factor, calibration, work solution and analyte amount are also assessed. The most relevant uncertainty sources result those associated to amount of mercury determined in the final sample solution, to method precision and to recovery. The relative contributions have different weights according to the analyst decision regarding recovery correction of results. In conclusion, the adopted CVAAS method fully complies with EU requirements. Presented at AOAC Europe/Eurachem Symposium March 2005, Brussels, Belgium     

Essential and inessential elements of a standard basis

In this paper we introduce the concept of inessential element of a standard basis B(I), where I is any homogeneous ideal of a polynomial ring. An inessential element is, roughly speaking, a form of B(I) whose omission produces an ideal having the same saturation as I; it becomes useless in any dehomogenization of I with respect to a linear form. We study the properties of B(I) linked to the presence of inessential elements and give some examples.