Design and Discovery of Plasmepsin II Inhibitors Using an Automated Workflow on Large‐Scale Grids

Novel and potent inhibitors of Plasmodium falciparum plasmepsin II were identified by post‐processing the results of a docking screening with BEAR, a recently reported procedure for the refinement and rescoring of docked ligands in virtual screening. FRET substrate degradation assays performed on the 30 most promising compounds resulted in 26 inhibitors with IC₅₀ values ranging from 4.3 nM to 1.8 μM .

     

Weaverbird: Topological Mesh Editing for Architects

Design and computation consultant Giulio Piacentino is the developer of WeaverBird. Here he describes how the plug-in ‘gives architects more geometric control and allows them to create complex surface structures that join in orderly ways, yet in arbitrary configurations’.     

Chemical characterisation of Thymus populations belonging from Southern Italy

The genus Thymus L. consists of many species of herbaceous perennials and sub-shrubs. A chemical characterisation of a collection of Thymus spp. originated from regions of Southern Italy was performed using GC and GC/MS. The accessions were collected from various natural habitats of the Basilicata and Puglia Regions and transferred into a new uniform environment. The study showed that amongst the 22 components of the oils the most recurrent ones were geraniol, thymol and α-terpinene followed by linalool, citral and trans-caryophillene. Cluster analysis led to the identification of two chemotypes: geraniol and thymol/α-terpinene; only a biotype remained separate from all others, probably because of its high content linalool (58%).     

Quercetin Administration Suppresses the Cytokine Storm in Myeloid and Plasmacytoid Dendritic Cells

Dendritic cells (DCs) can be divided by lineage into myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs). They both are present in mucosal tissues and regulate the immune response by secreting chemokines and cytokines. Inflammatory bowel diseases (IBDs) are characterized by a leaky intestinal barrier and the consequent translocation of bacterial lipopolysaccharide (LPS) to the basolateral side. This results in DCs activation, but the response of pDCs is still poorly characterized. In the present study, we compared mDCs and pDCs responses to LPS administration. We present a broad panel of DCs secreted factors, including cytokines, chemokines, and growth factors. Our recent studies demonstrated the anti-inflammatory effects of quercetin administration, but to date, there is no evidence about quercetin’s effects on pDCs. The results of the present study demonstrate that pDCs can respond to LPS and that quercetin exposure modulates soluble factors release through the same molecular pathway used by mDCs (Slpi, Hmox1, and AP-1).     

A 2D topology optimisation algorithm in NURBS framework with geometric constraints

In this paper, the solid isotropic material with penalisation (SIMP) method for topology optimisation of 2D problems is reformulated in the non-uniform rational BSpline (NURBS) framework. This choice implies several advantages, such as the definition of an implicit filter zone and the possibility for the designer to get a geometric entity at the end of the optimisation process. Therefore, important facilities are provided in CAD postprocessing phases in order to retrieve a consistent and well connected final topology. The effect of the main NURBS parameters (degrees, control points, weights and knot-vector components) on the final optimum topology is investigated. Classic geometric constraints, as the minimum and maximum member size, have been integrated and reformulated according to the NURBS formalism. Furthermore, a new constraint on the local curvature radius has been developed thanks to the NURBS formalism and properties. The effectiveness and the robustness of the proposed method are tested and proven through some benchmarks taken from literature and the results are compared with those provided by the classical SIMP approach.     

Gastric Adenocarcinomas and Signet-Ring Cell Carcinoma: Unraveling Gastric Cancer Complexity through Microbiome Analysis—Deepening Heterogeneity for a Personalized Therapy

Gastric cancer (GC) is the fifth most prevalent cancer worldwide and the third leading cause of global cancer mortality. With the advances of the omic studies, a heterogeneous GC landscape has been revealed, with significant molecular diversity. Given the multifaceted nature of GC, identification of different patient subsets with prognostic and/or predictive outcomes is a key aspect to allow tailoring of specific treatments. Recently, the involvement of the microbiota in gastric carcinogenesis has been described. To deepen this aspect, we compared microbiota composition in signet-ring cell carcinoma (SRCC) and adenocarcinoma (ADC), two distinct GC subtypes. To this purpose, 10 ADC and 10 SRCC and their paired non-tumor (PNT) counterparts were evaluated for microbiota composition through 16S rRNA analysis. Weighted and unweighted UniFrac and Bray–Curtis dissimilarity showed significant community-level separation between ADC and SRCC. Through the LEfSe (linear discriminant analysis coupled with effect size) tool, we identified potential microbial biomarkers associated with GC subtypes. In particular, SRCCs were significantly enriched in the phyla Fusobacteria, Bacteroidetes, Patescibacteria, whereas in the ADC type, Proteobacteria and Acidobacteria phyla were found. Overall, our data add new insights into GC heterogeneity and may contribute to deepening the GC classification.     

Sensory analysis integrated by palynological and physicochemical determinations plays a key role in differentiating unifloral honeys of similar botanical origins (Myrtaceae honeys from southern Spain)

Myrtaceae honeys produced in Sierra Morena (southern Spain, Andalusia) are obtained from both Eucalyptus camaldulensis and Myrtus communis, and honeys can be easily confused when classified as they come from the same botanical family. The characterisation was intended on the basis of their physicochemical, sensory and palynological properties. Cluster analysis (CA) and principal component analysis (PCA) allowed us to make a distinction between two honey profiles. The first one corresponds to the European sensory profile described for Eucalyptus unifloral honeys. The second profile, which sensory characteristics are absolutely different, has not been previously described. Classification of samples is proposed to be based on their pollen type and content and sensory attributes. Therefore, pollen type and content in E. camaldulensis and M. communis are required to distinguish Eucalyptus honey type from other honeys coming from Myrtaceae family. Sensory analysis identifies honey botanical source as well as palynological analysis: Eucalyptus sensory profile requires over 50% of E. camaldulensis and under 30% of M. communis pollen. Previously undefined sensory profile of myrtle honey is showed under 50% of E. camaldulensis and over 30% of M. communis pollen.     

A theoretically-based novel protocol for the analytic treatment of the glass failure stresses associated with coaxial double ring test method

With the aim of validating a new standardized Coaxial Double Ring testing procedure, without overpressure and with fixed geometry, an ad hoc theoretical approach has been proposed here to rearrange the laboratory outcomes accounting for the effects of the geometric non-linearities associated with such a testing configuration. By borrowing this idea, once the experimental values of the failure load have been determined, it has been possible to obtain an expression in closed form (fully defined by only two coefficients) of the maximum tensile stress (σ_max) in the core of the specimen. Following this, in order to make the laboratory outcomes comparable and homogeneous, the σ_max-values have been then re-scaled to a common reference condition (equibiaxial stress on a reference area, σ_eqbx), by means of the use of a correction coefficient (K) able to determine, under a condition of equal probability of failure, the effective area (A_eff) of the tested specimens. After being corrected to account for the effects of the stress corrosion cracking (static fatigue effect), all re-scaled data have been finally interpreted using a Weibull-type statistical distribution to determine the main fractile values of the glass strength. Doing so, despite some unavoidable approximations, this procedure furnished a highly effective means of determining the bending strength of float glass. Unlike the pure numerical approach proposed in codes and literature, which requires to correct the experimental data via FEM simulation, the rationale behind the proposed approach is in fact to elaborate the experimental data through an analytic treatment of the problem, which would greatly facilitate the interpretation of the data as well as the standardization of the testing procedure.     

Spatial agglomeration and productivity in Italy: A panel smooth transition regression approach

The paper analyses the nonlinearities in the impact of localization, diversity, urbanization and competition on firm‐level total factor productivity (TFP), using a large sample of Italian firms from 1999 to 2007. We adopt a panel smooth transition regression model, so that the TFP elasticities are free to vary smoothly across two or more extreme values. Results show that localization economies and Jacobian externalities materialize only for values of, respectively, intra‐industry agglomeration and extra‐sectoral diversity above a certain threshold. Local competition exerts a positive effect on productivity, even though the marginal impact shrinks at high levels of competition. We find instead no evidence of diseconomies of agglomeration.