INTEGRATION OF SURVEYING TECHNIQUES TO DETECT THE IDEAL SHAPE OF A DOME: THE CASE OF THE ESCUELAS PÍAS CHURCH IN VALENCIA

Abstract. The three-dimensional (3D) documentation and surveying of cultural heritage can be carried out following several geomatics techniques such as laser scanning and thermography in order to detect the original 3D shape after applying reverse engineering solutions. In almost all cases, the integration of data collected by different instruments is needed to achieve a successful and comprehensive 3D model of the as-built architectural shape of the historical building. This paper describes the operations carried out by the authors to determine the as-built 3D model of the Escuelas Pias Church, related namely to the dome and circular nave. After the description of the church and historical notes, attention will be driven to the indirect registration results obtained with three different laser scanning software packages, highlighting similarities and differences, and the consequences while generating meshes. The 3D model carried out will then be described and the results of some investigations with regard to the hypotheses about the design of the dome and the origin of the alterations will be presented.</p

The association of food ingredients in breakfast cereal products and fumonisins production: risks identification and predictions

Breakfast processed products are remarkably at risk of fungal contamination. This research surveyed the fumonisins concentration in different breakfast products, and carried out in-vitro experiments measuring fumonisins content in different substrates inoculated with Fusarium verticillioides. The pipeline started with the identification of combinations of ingredients for 58 breakfast products. Twenty-three core ingredients, seven nutritional components and production types were analyzed using a Pearson correlation, k-means clustering and principal component analysis to show that no single factor is responsible for high fumonisins detection in processed cereals products. Consequently, decision tree regression was used as a means of determining and visualizing complex logical interactions between the same factors. We clustered the association of ingredients in low, medium, and high risk of fumonisin detection. The analysis showed that high fumonisins concentration is associated with those products that have high maize concentrations coupled especially with high sodium or rice. In a in-vitro experiment, different media were prepared by mixing the ingredients in the proportion found in the first survey and by measuring fumonisins production by Fusarium verticillioides. Results showed that: 1) fumonisins production by F. verticillioides is boosted by the synergistic effect of maize and highly ready carbohydrate content such as white flour; 2) a combination of maize >26%(w/w), rice >2.5%(w/w), NaCl >2.2%(w/w) led to high fumonisins production, while mono-ingredient products were more protective against fumonisins production. The observations in the in-vitro experiments appeared to align with the decision tree model that an increase in ingredient complexity can lead to fumonisins production by Fusarium. However, more research is urgently needed to develop the area of predictive mycology based on the association of processing, ingredients, fungal development, and mycotoxins production

Structure-based virtual screening of novel natural alkaloid derivatives as potential binders of h-telo and c-myc DNA G-quadruplex conformations

Several ligands can bind to the non-canonical G-quadruplex DNA structures thereby stabilizing them. These molecules can act as effective anticancer agents by stabilizing the telomeric regions of DNA or by regulating oncogene expression. In order to better interact with the quartets of G-quadruplex structures, G-binders are generally characterized by a large aromatic core involved in pi-pi stacking. Some natural flexible cyclic molecules from Traditional Chinese Medicine have shown high binding affinity with G-quadruplex, such as berbamine and many other alkaloids. Using the structural information available on G-quadruplex structures, we performed a high throughput in silico screening of commercially available alkaloid derivative databases by means of a structure-based approach based on docking and molecular dynamics simulations against the human telomeric sequence d[AG(3)(T(2)AG(3))(3)] and the c-myc promoter structure. We identified 69 best hits reporting an improved theoretical binding affinity with respect to the active set. Among them, a berberine derivative, already known to remarkably inhibit telomerase activity, was related to a better theoretical affinity versus c-myc

Multi-Targeting Bioactive Compounds Extracted from Essential Oils as Kinase Inhibitors

Essential oils (EOs) are popular in aromatherapy, a branch of alternative medicine that claims their curative effects. Moreover, several studies reported EOs as potential anti-cancer agents by inducing apoptosis in different cancer cell models. In this study, we have considered EOs as a potential resource of new kinase inhibitors with a polypharmacological profile. On the other hand, computational methods offer the possibility to predict the theoretical activity profile of ligands, discovering dangerous off-targets and/or synergistic effects due to the potential multi-target action. With this aim, we performed a Structure-Based Virtual Screening (SBVS) against X-ray models of several protein kinases selected from the Protein Data Bank (PDB) by using a chemoinformatics database of EOs. By evaluating theoretical binding affinity, 13 molecules were detected among EOs as new potential kinase inhibitors with a multi-target profile. The two compounds with higher percentages in the EOs were studied more in depth by means Induced Fit Docking (IFD) protocol, in order to better predict their binding modes taking into account also structural changes in the receptor. Finally, given its good binding affinity towards five different kinases, cinnamyl cinnamate was biologically tested on different cell lines with the aim to verify the antiproliferative activity. Thus, this work represents a starting point for the optimization of the most promising EOs structure as kinase inhibitors with multi-target feature

SARS-CoV-2 variants and their relevant mutational profiles: update summer 2021

: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic caused by it, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been undergoing a genetic diversification leading to the emergence of new variants. Nevertheless, a clear definition of the genetic signatures underlying the circulating variants is still missing. Here, we provide a comprehensive insight into mutational profiles characterizing each SARS-CoV-2 variant, focusing on spike mutations known to modulate viral infectivity and/or antigenicity. We focused on variants and on specific relevant mutations reported by GISAID, Nextstrain, Outbreak.info, Pango, and Stanford database websites that were associated with any clinical/diagnostic impact, according to published manuscripts. Furthermore, 1,223,338 full-length high-quality SARS-CoV-2 genome sequences were retrieved from GISAID and used to accurately define the specific mutational patterns in each variant. Finally, mutations were mapped on the three-dimensional structure of the SARS-CoV-2 spike protein to assess their localization in the different spike domains. Overall, this review sheds light and assists in defining the genetic signatures characterizing the currently circulating variants and their clinical relevance. IMPORTANCE Since the emergence of SARS-CoV-2, several recurrent mutations, particularly in the spike protein, arose during human-to-human transmission or spillover events between humans and animals, generating distinct worrisome variants of concern (VOCs) or of interest (VOIs), designated as such due to their clinical and diagnostic impacts. Characterizing these variants and their related mutations is important in tracking SAR-CoV-2 evolution and understanding the efficacy of vaccines and therapeutics based on monoclonal antibodies, convalescent-phase sera, and direct antivirals. Our study provides a comprehensive survey of the mutational profiles characterizing the important SARS-CoV-2 variants, focusing on spike mutations and highlighting other protein mutations

HCV genotypes are differently prone to the development of resistance to linear and macrocyclic protease inhibitors

Because of the extreme genetic variability of hepatitis C virus (HCV), we analyzed whether specific HCV-genotypes are differently prone to develop resistance to linear and macrocyclic protease-inhibitors (PIs)