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Neurodegenerative diseases (NDDs) are progressive multifactorial disorders of the nervous system sharing common pathogenic features, including intracellular misfolded protein aggregation, mitochondrial deficit, and inflammation. Taking into consideration the multifaceted nature of NDDs, development of multitarget-directed ligands (MTDLs) has evolved as an attractive therapeutic strategy. Compounds that target the cannabinoid receptor type II (CB2R) are rapidly emerging as novel effective MTDLs against common NDDs, such as Alzheimer's disease (AD). We recently developed the first CB2R bitopic/dualsteric ligand, namely FD22a, which revealed the ability to induce neuroprotection with fewer side effects. To explore the potential of FD22a as a multitarget drug for the treatment of NDDs, we investigated here its ability to prevent the toxic effect of β-amyloid (Aβ25–35 peptide) on human cellular models of neurodegeneration, such as microglia (HMC3) and glioblastoma (U87-MG) cell lines. Our results displayed that FD22a efficiently prevented Aβ25–35 cytotoxic and proinflammatory effects in both cell lines and counteracted β-amyloid-induced depression of autophagy in U87-MG cells. Notably, a quantitative proteomic analysis of U87-MG cells revealed that FD22a was able to potently stimulate the autophagy–lysosomal pathway (ALP) by activating its master transcriptional regulator TFEB, ultimately increasing the potential of this novel CB2R bitopic/dualsteric ligand as a multitarget drug for the treatment of NDDs. [ABSTRACT FROM AUTHOR]

Epoxy resins are widely used polymers in the automotive and aerospace fields. Different blends of novel biodegradable resins have been studied in the last years in order to provide sustainability while maintaining the same properties of epoxy resins. Bio-based thermoset resins made with acrylated epoxidized soybean oil are well-studied in different vat polymerization techniques. The present work compares a bio-based resin and a petroleum-based resin. A benchmark with different features was designed and manufactured by a VAT photopolymerization process using both materials; measured with an optical scanning device; thus, the dimensional deviations were analyzed through inspection software. Tensile and flexural specimens were manufactured with the same procedure and tested with a dynamometer machine. Therefore, the comparison between a biodegradable resin and a petroleum-based resin is discussed in terms of the quality and mechanical performances of manufactured parts, considering the use of identical printing conditions. Some parts are required to satisfy both the requirements at the same time, such as the gears. Therefore, dimensional accuracy and mechanical strength need to be controlled and evaluated in a unique final quantification. This work proposes a novelty performance index to quantify dimensional accuracy and mechanical strength simultaneously. By combining the two aspects it is possible to define the overall performance obtained with the used material, optimizing the manufacturing process by choosing the proper material for each purpose. [ABSTRACT FROM AUTHOR]

Microglial dysfunction is one of the hallmarks and leading causes of common neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD). All these pathologies are characterized by aberrant aggregation of disease-causing proteins in the brain, which can directly activate microglia, trigger microglia-mediated neuroinflammation, and increase oxidative stress. Inhibition of glial activation may represent a therapeutic target to alleviate neurodegeneration. Recently, 3-iodothyronamine (T1AM), an endogenous derivative of thyroid hormone (TH) able to interact directly with a specific GPCR known as trace amine-associated receptor 1 (TAAR1), gained interest for its ability to promote neuroprotection in several models. Nevertheless, T1AM's effects on microglial disfunction remain still elusive. In the present work we investigated whether T1AM could inhibit the inflammatory response of human HMC3 microglial cells to LPS/TNFα or β-amyloid peptide 25–35 (Aβ25–35) stimuli. The results of ELISA and qPCR assays revealed that T1AM was able to reduce microglia-mediated inflammatory response by inhibiting the release of proinflammatory factors, including IL-6, TNFα, NF-kB, MCP1, and MIP1, while promoting the release of anti-inflammatory mediators, such as IL-10. Notably, T1AM anti-inflammatory action in HMC3 cells turned out to be a TAAR1-mediated response, further increasing the relevance of the T1AM/TAAR1 system in the management of NDDs. [ABSTRACT FROM AUTHOR]

During the additive manufacturing process, some geometrical deviations can arise, due to several thermomechanical phenomena that make residual stress rise. The study of dimensional and geometrical deviations connected with a manufacturing process is very important to achieve high-quality parts and to be able to assemble the obtained parts to arrive at assembly products with the desired functional requirements. This work aims to show a numerical procedure to predict the dimensional and geometrical deviations from the nominal of two parts in ABS material with a lattice structure inside an assembly that starts from the models of the parts obtained by simulating the material extrusion process. The idea is to control the volume of the lattice parts using the proposed measurement routines that take into account the surfaces of the lattice parts commonly used to couple them. Once virtually printed, the proposed numerical procedure converts each of the two parts constituting the assembly into a skin model shape representation to which least squares algorithms are applied to define dimensional and geometrical errors of the boundary surfaces of the part. The model was validated using a set of experimental tests; both the parts of the assembly were manufactured and their boundary surfaces were measured by a coordinate measuring machine. The obtained results were compared with those numerically obtained and a very good agreement was found. [ABSTRACT FROM AUTHOR]

Simple Summary: Electroporation is a method of treatment in which electrical pulses are generated and applied to a cell, resulting in temporary (reversible electroporation, RE) or permanent (irreversible electroporation, IRE) changes to the structure of the cell, depending on the pulse parameters applied. There has been increasing interest in manipulating the pulse parameters used to deliver successful electroporation for cutaneous malignancies in order to reduce muscle contractions and pain associated with traditional low-frequency electrochemotherapy (LF-ECT), which often requires general anaesthesia. Higher-frequency electroporation with biphasic waves successfully permeabilises the cell membrane, usually without causing these side effects, thus allowing treatment to be delivered under local anaesthetic. This permits a wide range of patients to be safely treated, including those for which general anaesthetic is a contra-indication. This article aims to demonstrate the safety and efficacy of high-frequency electroporation, as well as equivalence and good tolerability in comparison to traditional electrochemotherapy. High-frequency electroporation (HF-EP) with chemotherapy is a novel therapy proposed for both curative and palliative treatment of cutaneous malignancies. The use of high-frequency biphasic pulses is thought to reduce the painful muscle contractions associated with traditional electrochemotherapy (ECT), allowing treatment administration under local anaesthesia. This proof-of-concept study investigated the efficacy and tolerability of HF-EP protocols on a variety of cutaneous malignancies. A total of 97 lesions of five different histological subtypes were treated across 25 patients. At 12 weeks post-treatment, a 91.3% overall lesion response rate was observed (complete response: 79%; partial response: 12.3%), with excellent intraprocedural patient tolerability under local anaesthetic. HF-EP with chemotherapy shows promising results regarding tumour response rates for cutaneous malignancies of varying histological subtypes when compared to traditional ECT protocols. Improved patient tolerability is important, increasing the possibility of treatment delivery under local anaesthesia and potentially broadening the treatment envelope for patients with cutaneous malignancies. [ABSTRACT FROM AUTHOR]

Very recently, we have developed a new generation of ligands targeting the cannabinoid receptor type 2 (CB2R), namely JR compounds, which combine the pharmacophoric portion of the CB2R positive allosteric modulator (PAM), EC21a, with that of the CB2R selective orthosteric agonist LV62, both synthesized in our laboratories. The functional examination enabled us to identify JR14a, JR22a, and JR64a as the most promising compounds of the series. In the current study, we focused on the assessment of the bitopic (dualsteric) nature of these three compounds. Experiments in cAMP assays highlighted that only JR22a behaves as a CB2R bitopic (dualsteric) ligand. In parallel, computational studies helped us to clarify the binding mode of these three compounds at CB2R, confirming the bitopic (dualsteric) nature of JR22a. Finally, the potential of JR22a to prevent neuroinflammation was investigated on a human microglial cell inflammatory model. [ABSTRACT FROM AUTHOR]

This work investigates the thermal and electrochemical interaction of montmorillonite Clay (Mt) and a modified montmorillonite Clay (Mt-M) with a peptide sequence, which mimics the active site of the enzyme acetylcholinesterase, as well as their interactions with the chlorpyrifos pesticide. The methods used include thermal analysis techniques (DSC), X-ray diffraction, scanning electron microscopy, cyclic voltammetry, and electrochemical impedance spectroscopy. The electrochemical study was carried out in KCl 0.1 mol L−1, pH 7, containing a redox species Fe(CN)6–3/−4. The electrode surface coverage (θ ) was 0.42 for Mt and 0.65 for Mt-M. The interpretation of the electrochemical impedance spectroscopy results was based on the charge transfer reaction involving the [Fe(CN)6]−3/−4 species at high frequencies, followed by diffusion through the monolayer at low frequencies. The heterogeneity of the Mt and Mt-M film formed on electrode surface limits the transport of [Fe(CN)6]−3/−4 through the montmorillonite layer since the Mt particles formed non-regular overlapping plates, observed under microscopy. The DSC analyses revealed disorganization in the structure of the organophilic clay with the insertion of the pesticide, reflected in the appropriate waters of the system. [ABSTRACT FROM AUTHOR]

Geometric errors of parts affect not only the geometric deviations of the products obtained by assembling these parts through glue but also the mechanical strength of these products. Therefore, it is needed to investigate the relationship between geometrical deviations and the mechanical strength of assemblies due to a bonding process. In this work, the influence of adherends' misalignment on the 3- and 4-point flexural strength of a single-lap joint was investigated. A numerical model that considers the joint's geometric errors was developed and applied to different cases with different values of adhesive thickness and adherends' misalignment. The obtained results show that adherends' misalignment affects the performance of SLJs; in fact, the maximum load is always lower when SLJs have an adherends' misalignment. The numerical results were validated experimentally. The original contribution of the paper was to demonstrate numerically and experimentally the relationship between adherends' misalignment and flexural strength of single-lap bonded joints. [ABSTRACT FROM AUTHOR]

The image recapitulates the interplay between neuronal and vascular systems by highlighting the cellular players involved in the molecular signalling in the context of Amyotrophic Lateral Sclerosis. [Display omitted] The neurovascular system (NVS) is a complex anatomic-functional unit that synergically works to maintain organs/tissues homeostasis of the entire body. NVS alterations have recently emerged as a common distinct feature in the pathogenesis of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Despite their undeniable involvement, neurovascular signalling pathways remain still far unknown in ALS. This review underlines the importance of endothelial, mural, and fibroblast cells as novel targets for ALS investigation and identifies in the interplay between neuronal and vascular systems the way to disclose novel molecular mechanisms behind the pathogenesis of ALS. [ABSTRACT FROM AUTHOR]

The paper describes a general adaptive sampling methodology useful in multivariate optimization involving finite element analysis that typically requires a long time. The proposed adaptive sampling method was obtained by starting from a model-based statistical methodology developed to design an adaptive inspection plan for the geometric control of mechanical parts. The novelty of the new kriging adaptive sampling procedure consists in overcoming some critical issues, such as the reduction of the estimation time to have an efficient tool for quick application. The others are related to how to set up a kriging-based adaptive sampling, how to choose the stopping rule, and how to remove the dependence on the statistical variability. These issues are the subject of this work to develop a useful tool for multivariate optimization. By improving the methodology in these aspects, it was possible to obtain a feasible and useful instrument for the application in a quick sampling procedure within the inspection process. After this enhancement process, the method is sufficiently general to be extended in the multivariate optimization field that requires a multi-factorial finite element analysis. To demonstrate this, an illustrative real case study from an industrial application is presented and it was found that the proposed method reduces significantly the time required to reach the optimal solution. [ABSTRACT FROM AUTHOR]

Superplastic forming has drawn growing interest from both automotive and aeronautical fields. It allows to decrease the weight of the product by eliminating fasteners because it can be used to form components with complex shapes that are very close to that of the final product; it can be considered a near-net-shape forming process. This work shows the optimal design of the thicknesses of a blank in AZ31 superplastic magnesium-based alloy to form a complex-shaped product. The adopted optimization method changed a set of geometric parameters of the blank to find the values that make as uniform as possible the final distribution of the product thicknesses. This method led to a blank with a variable thickness. The design was assisted by finite element analysis. The optimized process allowed to obtain, if it is compared to the same superplastic forming process on a blank with a constant thickness, (i) a final product characterized by a more uniform thickness distribution, (ii) a reduction of forming time, and (iii) a reduction of the product weight. It was carried out an experimental activity too that confirmed the convenience of adopting a blank with a variable thickness on which to carry out the forming process. [ABSTRACT FROM AUTHOR]

Purpose: Selective laser sintering (SLS) has passed other techniques, thanks to its high print resolution, its ability to print microscale geometries without any additional support, its surface quality and its long-term thermal stability. However, despite the many advantages of SLS compared to fusion deposition modelling, there are still today some limitations on the materials to be printed. A limit critical from an industrial point of view is the aging of PA12 powder, i.e. the degradation of its physical and chemical performances, due to the high temperatures and the long printing cycles, thus involving a decrease of the mechanical properties of the printed parts. The purpose of this study was to charaterize mechanically and dimensionally specimens printed in PA12 through SLS by means of virgin or aged powder, i.e. powder just used for five printing cycles. Design/methodology/approach: To achieve this aim, a set of specimens were designed, built, measured and mechanically tested; the obtained results were put into relationship with the values of the process parameters used to print them. Statistical tools to design the experiments and to analyse the obtained results were used. Findings: The results show that the SLS process carried out through a Sintratec machine on PA12 powder has a good repeatability. To obtain the best dimensional and mechanical performances, it is needed to use virgin powder and place the part in the central zone of the printing area. Originality/value: There are no scientific articles dealing with the influence of both the aging of the powder and the manufacturing parameters on the dimensional and mechanical characterization of specimens printed with SLS technique in PA12. [ABSTRACT FROM AUTHOR]

The present work compares two numerical tools to predict the geometrical deviations of an assembly constituted by thin laminates in composite material. The first one is based on a virtual representation of both the manufacturing and the assembling processes, able to generate the variability meta-model for each component to be used in a skin-based assembly. The second one estimates the sensitivity matrix that connects the components' variations to the assembly's variations in the method of influence coefficients (MIC). They were experimentally verified on a case study. The comparison underlined the critical issue of both the tools. [ABSTRACT FROM AUTHOR]

For a projective variety V ⊂ P k n over a field of characteristic zero, with homogeneous ideal I in A = k [ x 0 , ... , x n ] , we consider the local cohomology modules H I i (A). These have a structure of holonomic D -module over A , and we investigate their filtration by simple D -modules. In case V is nonsingular, we can describe completely the simple D -module components of H I i (A) for all i , in terms of the Betti numbers of V. [ABSTRACT FROM AUTHOR]

Compressible electron flow through a narrow cavity is theoretically unstable, and the oscillations occurring during the instability have been proposed as a method of generating terahertz radiation. We numerically demonstrate that the end point of this instability is a nonlinear hydrodynamic oscillator, consisting of an alternating shock wave and rarefaction-like relaxation flowing back and forth in the device. This qualitative physics is robust to cavity inhomogeneity and changes in the equation of state of the fluid. We discuss the frequency and amplitude dependence of the emitted radiation on physical parameters (viscosity, momentum relaxation rate, and bias current) beyond linear response theory, providing clear predictions for future experiments. [ABSTRACT FROM AUTHOR]

The industry is facing the management of manufacturing processes along the entire lifecycle of the product. It is helped by digital twin tools that may minimize the out of control of processes. Information and communication technologies help digital twin tools to monitor manufacturing performances. In this way, a continuous and unambiguous flow of information flows along the whole product lifecycle along digital process. They are based on data coming from manufacturing and inspection. Actually, no digital twin tool exists that assists machining of ornamental stones. Moreover, the models proposed by the literature take into account a unique aspect of the manufacturing process, such as the control of the cutting force and energy or the monitoring of the tool wear and, therefore, it does not exist a continuous flow of information from cutting force to tool monitoring. The present work introduces a digital twin tool to manage force, energy, and tool wear during machining of ornamental stone. It uses high-fidelity models for simulation that were widely experimentally tested. It establishes a continuous and unambiguous flow of information from machine to tool, and from cutting force and energy estimation to tool wear prediction. It was applied to two case studies and the obtained results agree with the experimental ones. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this paper is to present a skin-based approach able to generate the variability model for a component in composite material due to its manufacturing process. It generates a skin-based model of the manufactured part. The skin model discretizes the part surfaces by points to take into account the geometric deviations, those points are the nodes of finite element analysis used for tolerance analysis of compliant assemblies. Design/methodology/approach: The paper presents a general and systematic simulation model for generating a variability meta-model for a component in composite material due to its manufacturing process. The model is constituted by three steps: definition and pre-processing of the nominal model, generation of the manufacturing process model and evaluation of the part variability. Findings: The advantage of this approach is related to the fact that it is designed as a part of a digital process that establishes a continuous and unambiguous flow of variation information from the part design to manufacturing and assembly and that takes into account the manufacturing signature. This is its uniqueness compared to other simulation approaches focused only on manufacturing. Research limitations/implications: Considering the variability around the nominal value of all the process parameters and parts with more complex geometries are not taken into account now, which will be modelled in practical applications. Practical implications: To properly manage uncertainty since conceptual design of complex product, next generation geometry assurance requires simulation models to realistically consider process signatures due to the manufacturing process. This work focusses on this next generation tool for geometry assurance. Originality/value: The literature is focused on metal sheets joined by welding or riveting. There are other materials widely used and typically compliant: the composite materials that typically used mechanical fixing elements (bolting, riveting) and structural adhesives to joint parts. No software tools exist in the literature to deal with uncertainty from manufacturing to assembly processes in products made by composite. This is the reason of the present work. [ABSTRACT FROM AUTHOR]

It has long been known how to read information about the socle degrees of the local cohomology H0m(M) of a graded module over a polynomial ring R from the twists in position d = dimR, in a resolution of M by free R-modules. It has also long been known how to use local cohomology to read valuable information from complexes which approximate resolutions in the sense that they have positive homology of small Krull dimension. The present paper reads information about the maximal generator degree (rather than the socle degree) of H0m(M) from the twists in position d - 1 (rather than position d) in an approximate resolution of M. We apply the local cohomology results to draw conclusions about the maximal generator degree of the second symbolic power of the prime ideal defining a monomial curve and the second symbolic power of the ideal defining a finite set of points in projective space. There is also an application to hyperplane sections of subschemes of projective space and to partial Castelnuovo-Mumford regularity. Perhaps, the most important application is to the study of blow-up algebras and their defining equations. The techniques of the present paper are the main tool used in Kustin, Polini and Ulrich [Algebra Number Theory 11 (2017) 1489-1525] to bound the degrees of these equations and thus to identify them in some cases. [ABSTRACT FROM AUTHOR]

L'articolo discute il legame tra valutazione e apprendimento nell'ambito delle politiche pubbliche, focalizzando l'attenzione su un'esperienza formativa rivolta agli operatori delle migrazioni. L'approccio costruttivista utilizzato in questa esperienza si ricollega a un uso conoscitivo della valutazione, attraverso cui si è dipanato un percorso di riflessività e partecipazione. Il contributo presenta alcuni dei risultati di un corso di formazione in cui gli operatori delle migrazioni hanno appreso come modificare le loro prassi a seguito delle recenti riforme in materia di immigrazione e ne hanno tratto suggerimenti di policy. [ABSTRACT FROM AUTHOR]

The limits of a sheet metal stretching process are mainly two: i) it determines tears in a little formable material; ii) it produces a non-uniform thickness distribution in the formed component. For this reason, this work presents encouraging preliminary experimental results on a stretching process of an aluminium alloy sheet that has a variable thickness. This sheet was machined by removing material from a commercial sheet of constant thickness. The obtained results show how the use of a sheet with a variable thickness allows to increase the material formability and to manufacture a product characterized by a more uniform thickness. [ABSTRACT FROM AUTHOR]

Advances in materials science have made it possible for electrons in metals to exhibit exotic hydrodynamic effects. [ABSTRACT FROM AUTHOR]

The most used approach to solve tolerance analysis problems for flexible assemblies is the method of influence coefficients that combines the finite element analysis with statistical analysis in order to establish a relationship between the assembly deviation and part deviation and to foresee the statistical distribution of stresses. The key of this relationship is the sensitivity matrices for the deviations and stresses that can be evaluated by different methods of influence coefficients. Therefore, the aim of this work is to make a review of these methods applying them to evaluate some flexible assemblies on the statistical distribution of deviations and stresses. [ABSTRACT FROM AUTHOR]

Adhesively bonded joints are widely used in the design of structures due to the high strength-to-weight ratio. The entire literature generally investigates on how to improve the strength of adhesive joints because the use of adhesive joints is increasing in many industries. However, the strength of adhesive joints depends on the geometric errors of parts to be joined, the bonding process and the equipment used to join the parts. This work aims to numerically investigate how a possible error due to the bonding process influences the strength of the adhesive joint. The single-lap joint was used as a type of joint due to its simple geometry, and the adherends misalignment was considered as error due to the bonding process. Considering the single-lap joint as an assembly made of two adherends and an adhesive, it is possible to reason in terms of tolerance analysis where, varying the geometry of the adherends, it is possible to evaluate how it influences the strength of the adhesive joint. In order to perform this analysis, a numerical tool, based on FEA and MATLAB® software packages, was used to manage the geometrical deviations of the adherends. The effect of the adherends misalignment on the reduction of the strength of the adhesive joint was testified by experimental tests. [ABSTRACT FROM AUTHOR]

Messenger RNA (mRNA) and microRNA (miRNA)-based therapeutics have become attractive alternatives to DNA-based therapeutics due to recent advances in manufacture, scalability and cost. Also, RNA-based therapeutics are considered safe since there are no risk of inducing genomic changes as well as the potential adverse effects would be only temporary due to the transient nature of RNA-based therapeutics. However, efficient in vivo delivery of RNA-based therapeutics remains a challenge. We have developed a delivery platform for RNA-based therapeutics by exploiting the physicochemical properties of enveloped viruses. By physically attaching cationic liposome/RNA complexes onto the viral envelope of vaccinia virus, we were able to deliver mRNA, self-replicating RNA as well as miRNA inside target cells. Also, we showed that this platform, called viRNA platform, can efficiently deliver functional miRNA mimics into B16.OVA tumour in vivo. [ABSTRACT FROM AUTHOR]

Abstract We derive numerical estimates controlling the intertwined properties of the normalization of an ideal and of the computational complexity of general processes for its construction. In [18] , this goal was carried out for equimultiple ideals via the examination of Hilbert functions. Here we add to this picture, in an important case, how certain Hilbert functions provide a description of the locations of the generators of the normalization of ideals of dimension zero. We also present a rare instance of normalization of a class of homogeneous ideals by a single colon operation. [ABSTRACT FROM AUTHOR]

The cure process of carbon fiber-reinforced polymer laminates induces residual stress inside the parts that causes geometrical unconformities. The most important unconformity is the spring-in that means the deviation of the flange-to-flange angle from the design angle. The spring-in value depends on some process parameters, such as the lay-up sequence of the plies, as demonstrated in previous works. The aim of this work is to study the dependence of the spring-in on the deviations in the orientation of the plies due to a hand process. A numerical tool was developed and experimentally tested. [ABSTRACT FROM AUTHOR]

High-flexibility components in composite material are of great interest in many fields, from aeronautic and automotive industries to sport and design goods. Their deformation during cure process, known as spring-in and warpage, is acceptable if it is within the indicated tolerance. The research aim of the present work is to present a way to inspect a high flexible part in composite material by means of a coordinate measuring machine with a touch probe. This means to define the fixturing equipment and the measurement strategy. The developed method was applied to an L-shaped part with a very small thickness and the obtained measurements were compared with those due to a laser system. The results show a good agreement between the two measurement techniques. Moreover, the further numerical simulations validate the developed contact measurement method. [ABSTRACT FROM AUTHOR]

• Synthesis of nanostructured scheelite (CaWO 4) from wolframite enriched ores. • Mechanochemical activation of wolframite and calcium carbonate (CaCO 3) mixtures. • Quantitative conversion of wolframite and CaCO 3 mixtures into CaWO 4 at T ≤ 700 °C. • No need of CaCO 3 excess to get complete conversion of wolframite into CaWO 4. Nanostructured scheelite (CaWO 4) was synthesized by calcination in air of enriched wolframite (Fe 1−x Mn x WO 4) ore and calcium carbonate (CaCO 3). The effects of process parameters such as milling conditions of the solid reactants, calcination in flowing or static air, and use of stoichiometric excess of calcium carbonate on wolframite conversion into scheelite were studied by X-Ray Diffraction (XRD) and field emission gun scanning electron microscopy (FEG SEM). The intimate mixing and associated decrease in the diffusion path by high-energy planetary ball milling (PBM) were responsible for the conversion of most of wolframite into nanostructured scheelite after 2 h at 600 °C, with no need of calcium carbonate stoichiometric excess. Complete conversion of PBM wolframite:CaCO 3 mixtures into nanosized scheelite, iron oxide and carbon dioxide was accomplished after 2 h at 700 °C. The nanostructured scheelite obtained from wolframite is expected to be significantly more reactive in subsequent treatments (e.g., leaching) for tungsten extraction. [ABSTRACT FROM AUTHOR]

Cutaneous melanoma is a skin cancer with increasing incidence. Identification of novel clinical biomarkers able to detect the stage of disease and suggest prognosis could improve treatment and outcome for melanoma patients. Cell‐free microRNAs (cf‐miRNAs) are the circulating copies of short non‐coding RNAs involved in gene expression regulation. They are released into the interstitial fluid, are detectable in blood and other body fluids and have interesting features of ideal biomarker candidates. They are stable outside the cell, tissue specific, vary along with cancer development and are sensitive to change in the disease course such as progression or therapeutic response. Moreover, they are accessible by non‐invasive methods or venipuncture. Some articles have reported different cf‐miRNAs with the potential of diagnostic tools for melanoma staging, recurrence and survival prediction. Although some concordance of results is already emerging, differences in analytical methods, normalization strategies and tumour staging still will require further research and standardization prior to clinical usage of cf‐miRNA analysis. This article reviews this literature with the aim of contributing to a shared focusing on these new promising tools for melanoma treatment and care. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this paper is to model how geometric errors of a machined surface (or manufacturing errors) are related to locators' error, workpiece form error and machine tool volumetric error. A kinematic model is presented that puts into relationship the locator error, the workpiece form deviations and the machine tool volumetric error. Design/methodology/approach: The paper presents a general and systematic approach for geometric error modelling in drilling because of the geometric errors of locators positioning, of workpiece datum surface and of machine tool. The model can be implemented in four steps: (1) calculation of the deviation in the workpiece reference frame because of deviations of locator positions; (2) evaluation of the deviation in the workpiece reference frame owing to form deviations in the datum surfaces of the workpiece; (3) formulation of the volumetric error of the machine tool; and (4) combination of those three models. Findings: The advantage of this approach lies in that it enables the source errors affecting the drilling accuracy to be explicitly separated, thereby providing designers and/or field engineers with an informative guideline for accuracy improvement through suitable measures, i.e. component tolerancing in design, machining and so on. Two typical drilling operations are taken as examples to illustrate the generality and effectiveness of this approach. Research limitations/implications: Some source errors, such as the dynamic behaviour of the machine tool, are not taken into consideration, which will be modelled in practical applications. Practical implications: The proposed kinematic model may be set by means of experimental tests, concerning the industrial specific application, to identify the values of the model parameters, such as standard deviation of the machine tool axes positioning and rotational errors. Then, it may be easily used to foresee the location deviation of a single or a pattern of holes. Originality/value: The approaches present in the literature aim to model only one or at most two sources of machining error, such as fixturing, machine tool or workpiece datum. This paper goes beyond the state of the art because it considers the locator errors together with the form deviation on the datum surface into contact with the locators and, then, the volumetric error of the machine tool. [ABSTRACT FROM AUTHOR]

Geometric accuracy is a critical performance factor for machining, especially when one of the basic requirements is high precision. In this paper, a general and systematic approach is shown to model hole geometric deviation from nominal due to the geometric errors of three important elements of the drilling process: the locators, the workpiece datum surface and the machine tool. The proposed approach was used for calculating the deviation from nominal of lots of drilled holes on a plate in order to evaluate the influence of the locator errors, of the form deviation of the part datum surfaces and of the volumetric error of the machine tool. Those parameters' influence was evaluated through a design of experiments technique with a factorial plane implemented in a Matlab® file, allowing a saving of time, energy and material. It was found that the volumetric error of the machine tool influenced mainly the drilled hole location deviation from nominal. [ABSTRACT FROM AUTHOR]

In manufacturing industry, products are obtained by joining/assembling together parts or sub-assemblies. The geometric deviation of a single part, due to inherent process variability, propagates through the process chain to the final assembly and, therefore, affects the quality and the functional compliance of the final product. According to the literature, up to 70% of design changes or failures are caused by the inaccurate prediction of the geometric deviations of the final products. Therefore, the ability to predict the geometric variation of a final product is a major challenge in many manufacturing sectors. There are no consolidated methodologies in the literature to predict the variability (uncertainty) of products constituted by compliant parts of any material during the design stage, thus the relevant need for a solution. This work uses a numerical tool to predict the uncertainties resulting in manufacturing products constituted by compliant lightweight parts in composite material joined by means of an adhesive. To compare and validate the numerical tool, an experimental activity was carried out. The obtained results show that the numerical tool allows to reproduce the mean trend of the geometrical deviations of the assembly. [ABSTRACT FROM AUTHOR]

One of the obstacles for composite applications is the geometry assurance. Traditional dimension control operations for composites are mainly based on trial-and-error approaches, which cannot be directly and effectively employed in real-world part design and tooling development. With the increasing requirement for composite products to be affordable, net-shaped, assembly efficient, and effective dimension control is highly desirable. Currently, composite components cannot be processed to the tolerance level required for an assembly because of the lack of dimension control. Better dimensional control can improve assembly, reduce extra processing steps, and make parts interchangeable for rapid repair and retrofit. Variation analysis represents the best way to solve these assembly problems in order to ensure higher quality and lower costs, but few studies have focused on this issue. Therefore, the aim of this work is to experimentally solve an assembly constituted by parts in composite material and joined by adhesive in order to use these results to validate a numerical tool for variation analysis of compliant part. [ABSTRACT FROM AUTHOR]

Highlights • Immune system plays a critical role in maintaining homeostasis of the human body. • Development of immune-system-on-a-chip platforms is in its infancy. • Several platforms emulate lymphoid organs and immune component-integrated tissues. • Reproducing complexity and tissue interactions is key to engineering such platforms. • Immune-system-on-a-chip platforms will enable personalized immunoscreening. Organ-on-a-chip (OoCs) platforms could revolutionize drug discovery and might ultimately become essential tools for precision therapy. Although many single-organ and interconnected systems have been described, the immune system has been comparatively neglected, despite its pervasive role in the body and the trend towards newer therapeutic products (i.e., complex biologics, nanoparticles, immune checkpoint inhibitors, and engineered T cells) that often cause, or are based on, immune reactions. In this review, we recapitulate some distinctive features of the immune system before reviewing microfluidic devices that mimic lymphoid organs or other organs and/or tissues with an integrated immune system component. [ABSTRACT FROM AUTHOR]

Abstract During the cure process, the anisotropic characteristics of composite material, combined with high temperature and high pressure to which the material is subjected, cause the development of residual stresses. Consequently, laminate deformations arise and dimensional and geometrical requirements are not reached. Laminate deformations transfer into product distortions through assembly process. Distortions result in uncertainty in the performance of manufactured goods and they require effective management to ensure correct performance. The present work shows a numerical approach suitable to determine the geometrical deviations of an assembly constituted by thin laminates in composite material. The proposed model considers the geometrical deviations of the assembly parts, due to the manufacturing process, the assembly sequence and the presence of adhesive to put together the parts. The proposed model was experimentally verified by considering a T-shaped assembly constituted by flat and L-shaped components. The obtained results show a good agreement with the experimental ones. [ABSTRACT FROM AUTHOR]

Abstract Hydrogels are the preferred material choice for various strategies in regenerative medicine. Nevertheless, due to their high water content and soft nature, these materials are often mechanically weak, which limits their applicability. This study demonstrates mechanical reinforcement of colloidal gels at microscale using discrete polyester fibers, as confirmed by rheological, compression and nanoindentation tests. This reinforcement strategy results in injectable and moldable colloidal gels with improved mechanical performance. The fully organic gels presented here are cytocompatible and can maintain their mechanical integrity under physiological conditions. Consequently, these gels exhibit a strong potential for applications in tissue engineering and regenerative medicine. Graphical abstract Unlabelled Image Highlights • Colloidal gels are mechanically reinforced using discrete polyester fibers. • The resulting gels are injectable, moldable, and cytocompatible. • These gels exhibit a strong potential for applications in regenerative medicine. [ABSTRACT FROM AUTHOR]

Nowadays composite materials play a leading role in structural design, particularly in aeronautics and automotive. In these industries, to reduce the weight of the components maintaining the same performance is most required. With this in mind, the use of structural adhesives allows to maximize the specific strength of assembled parts. To have a thorough knowledge of the various influencing parameters is necessary in order to design bonded components. In particular, surface treatments play a key role in joint strength. Understanding the best combinations of adherend - adhesion surface - adhesive allows designing bonded components more easily and reliably. This work analyses the influence of surface treatment of CFRP adherends on mechanical strength and breaking morphology. In particular, SLJ (Single Lap Joints) specimens were made with both film and paste adhesives. It has been noted that the combination between adhesive and surface treatment influenced the failure morphology and mechanical strength. [ABSTRACT FROM AUTHOR]

Abstract Although the anticancer properties of extra virgin olive oil (EVOO) extracts have been recognized, the role of single compounds in non-melanoma skin cancer is still unknown. The in vitro chemopreventive and anticancer action of EVOO extracts and oil-derived compounds in non-melanoma skin cancer models were evaluated on cutaneous squamous cell carcinoma cells and on immortalized human keratinocytes stimulated with epidermal growth factor. Preparation of EVOO extracts and isolation of single compounds was carried out by chromatographic methods. Antitumor activity was assessed by cell-based assays (cell viability, migration, clonogenicity, and spheroid formation) and apoptosis documented by internucleosomal DNA fragmentation. Finally, inhibition of key oncogenic signaling nodes involved in the progression from actinic keratosis to cutaneous squamous cell carcinoma was studied by western blot. EVOO extracts reduced non-melanoma skin cancer cell viability and migration, prevented colony and spheroid formation, and inhibited proliferation of atypical keratinocytes stimulated with epidermal growth factor. Such a pharmacological activity was promoted by oleocanthal and oleacein through the inhibition of Erk and Akt phosphorylation and the suppression of B-Raf expression, whereas tyrosol and hydroxytyrosol did not have effect. The current study provides in vitro evidence for new potential clinical applications of EVOO extracts and/or single oil-derived compounds in the prevention and treatment of non-melanoma skin cancers. Highlights • Extra virgin olive oil (EVOO) extracts exert anticancer activity on squamous cell carcinoma. • EVOO extracts prevent proliferation of atypical human keratinocytes stimulated with EGF. • EVOO extracts reduce protein expression of B-Raf and phosphorylation of Erk 1/2 and Akt. • Oleocanthal and oleacein contribute to the anticancer effects by phytoextracts. [ABSTRACT FROM AUTHOR]

Tolerance analysis defines a procedure to estimate the resultant variation of the assembly geometry, given the tolerances associated with individual components and the functional relationship between the individual components and the assembly requirements. This aspect is particularly relevant when parts made of composite material are considered, since the research emphasis to date was on the design and fabrication of composite parts, with considerably less attention to quality issues in their subsequent assembly. This work presents a numerical tool to solve the tolerance analysis of assemblies made of compliant parts in composite material; it estimates the geometric deviations of an assembly due to the compliance of the material, the geometrical deviations of the components and the fastening of the parts by adhesive. The comparison between numerical and experimental results obtained for a case study shows a good agreement. [ABSTRACT FROM AUTHOR]

Focuses on a model kinetics that should represent a guideline for describing the nucleation process at solid substrate as it occurs in the chemical vapor deposition process. Processes comprising the kinetic scheme; Conditions of low surface coverage; Application to diamond deposition.

This study aimed at investigating the thermal and electrochemical behavior of montmorillonite clay-8-hydroxyquinoline (8-HQ) film in the absence and presence of aqueous Fe(III) ions. The solid film characterization by means of UV spectroscopy, thermal (TG/DTG and TG-DTA, simultaneous) studies, SEM and optical images, and XRD suggested the formation of the ternary complex type: {Pt/[>Si-O][Fe(III)(OH)(8-HQ)]}, with thermal stability up to 300 °C. The electrochemical study was carried out on a platinum electrode modified by mechanical deposition of a thin solid film of the binary composite (SWy-1:8-HQ) from an aqueous suspension. The mechanical stability of the film was followed by performing 80 cyclic voltammograms. The electrochemical behavior of the modified electrode was investigated using cyclic voltammetry (CV) at different ferric ions concentration ( C )), followed by a study of the effect of the scan rate ( v) with a fixed C ions. In the CVs, two independent pairs of current peaks, A/D and C/B, were observed. For Fe(III) ions in solution, log i versus log v relationship shows a process controlled first by adsorption (pair of peaks A/D) and then by diffusion control (pair of peaks C/B). The current function i / v versus v and i / i versus v allowed a suggestion of two homogeneous coupled chemical reactions associated with CE and EC mechanisms, respectively, both with fast reversible chemical reactions. The first investigation of a modified electrode showed good sensitivity ( S = 25.1 μA/μmol L) to low concentrations of ferric ions and detection limit [LOD = (2.4 ± 0.01) μmol L] and high sensitivity to traces of O, showing that this system has great analytical potentials. [ABSTRACT FROM AUTHOR]

The thermal and electrochemical behavior of montmorillonite clay-8-hydroxyquinoline (8-HQ) film was studied in the absence and presence of aqueous Cu(II) ions. The suggested formation of the ternary complex type: {Pt/[> Si-O][Cu(II)(OH)(8-HQ)]}, with thermal stability up to 350 °C, was studied, based on UV-spectroscopy, thermal (DTG-DSC, molecular fluorescence and XRD. The Pt/binary composite film (SWy-1:8-HQ) interphase composed of montmorillonite (SWy-1) with 8-hydroxyquinoline (8-HQ) was investigated by electrochemical techniques analyzing the cyclic voltammograms (CVs) obtained at different scan rates (v) and copper(II) ion concentrations. The mechanical stability of the thin films was demonstrated by performing 80 successive voltammetric cycles. Two pairs of redox peaks, indicated by peaks A/D and C/B were observed. For Cu(II) ions in solution, the log i × log v relationships showed processes controlled by adsorption, peaks A/D, and by diffusion, peaks C/B. The analysis of i / v and i / i versus v suggested two homogeneous coupled reactions, being both reversible and fast kinetic chemical reactions, associated to the mechanisms chemical-electrochemical (CE) and electrochemical-chemical (EC), respectively. The modified electrode showed a good sensitivity to low concentrations of Cu(II) ions, which opens the possibility of being used in chemical analysis. [ABSTRACT FROM AUTHOR]

The need of a univocal language for geometrical product specification considering all steps of the product life cycle such as design, manufacturing, and inspection is inevitable. Most models for Computer-Aided Tolerancing proposed by researchers and used in industry do not fully conform with standards. Moreover, most of them make severe assumptions on observable geometric deviations and can therefore hardly handle all kinds of 3D tolerances. These lacks inspired the idea and the development of a discrete geometry framework that is capable of considering geometric deviations of different stages of the product life cycle and is versatile regarding current and future tolerancing standards. This work uses a point cloud-based geometry representation scheme to implement the pattern left on the surfaces by a manufacturing process; then, this scheme has been inserted in a variational approach for tolerance analysis. Moreover, gravity and friction among the parts to assemble have been simulated too. In this way, a new Computer Aided Tolerancing (CAT) simulation tool has been developed; it approaches reality more than existing software packages do. To verify the effectiveness of the new CAT simulation tool, it has been applied to two case studies. The obtained results have been compared with those due to a geometrical model that has been developed by simulating what happens among the parts in the actual assembly. The obtained results show how the new CAT simulation tool gives results nearer to reality than literature models do. [ABSTRACT FROM AUTHOR]

An analytical mean field approach for describing the time evolution of film growth by seeding has been developed. The modeling deals with the generic case of anisotropic growth with different growth rates, respectively on – and normal to – the substrate plane. The finite size of the seeds is considered by including spatial correlation effects among seeds through hard-core interactions. The approach, based on probability theory, provides solution in closed form for mean film thickness as a function of substrate coverage, seed density and initial size of the seeds. For negligible values of the initial coverage of the substrate by seeds, manageable analytical expressions are attained. The model has been validated by comparison with experimental data available in the literature. This study is significant in connection to the possibility of determining optimal growth conditions for ultrathin nanocrystalline diamond (NCD) film. In fact, the knowledge of the seeding/nucleation density that allows a given minimum average thickness of continuous film is of utmost importance for the development of technologically advanced applications. [Display omitted] • Analytical approach for critical thickness of films grown via seeding • Spatial correlation effects due to the finite size of seeds are modeled. • Evaluation of the seed density needed to get a thin film with a desired thickness • Assessment of the stability of seeds under CVD conditions [ABSTRACT FROM AUTHOR]

Pure scheelite (CaWO 4 ) and carbon black mixtures, containing either 0–6 wt% cobalt or 0–2 wt% nickel were prepared by 24 h planetary ball milling (PBM). CaWO 4 :C mixtures were then subjected to 1 h annealing at 1200 or 1400 °C in tubular furnace under flowing Ar (heating ramp: 3 °C/min). Following the carbothermic reduction, the obtained powders were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). CaWO 4 :C mixtures with no added metal gave an almost quantitative WC yield (≥ 96%) after 1 h annealing at both temperatures. All mixtures containing Co or Ni gave rise to a WC yield exceeding 99% after annealing at 1400 °C. Mixtures annealed at 1200 °C exhibited a slightly lower yield, being the estimated percentage of WC ≥ 98% with cobalt dopant, and 95% with 2 wt% Ni. For the first time we here show that Co or Ni addition has a noteworthy effect on the size of WC particles produced by carbothermic reduction of CaWO 4 and subsequent leaching with diluted hydrochloric acid. In particular, the size of WC particles could be tailored from 0.2–0.3 μm to 2–3 μm when Co was increased from 0 to 5–6 wt% and the reaction temperature raised to 1400 °C. These findings are particularly appealing from both industrial and sustainability point of view, since they further validate the carbothermic reduction of scheelite as a simpler, cheaper and less energy-intensive process for the synthesis of nano- and micro-structured WC powders to be employed for manufacturing different hardmetal grades. [ABSTRACT FROM AUTHOR]

Objective: Varenicline (VCL) treatment has become popular as a part of smoking-cessation therapies, even though its possible implications in neuropsychiatric adverse events include abnormal sleep and nightmares. Our study is the first aimed at prospectively investigating changes in sleep and dream measures across such treatment by using a one week sleep diary and collecting dream recall (DR).Methods: Thirty-eight smokers participated in two different effective smoking-cessation programs: 25 subjects received VCL, 13 subjects received nicotine replacement therapy (NRT). Participants were requested to fill out a sleep diary and audio-record dreams for one week, both at baseline assessment (T0) and after two weeks from the beginning of treatment (T1). Differences in sleep and dream measures were tested using mixed Analysis of Covariance with time (T0 vs T1) as a within-subject factor and group (VCL vs NRT) as a between-subject factor, considering age as a covariant.Results: Sleep measures showed a significant increase in the number of awakenings in the VCL group at T1 compared to T0. The VCL group reported an increase in DR rate at T1. These sleep and dream measures were intercorrelated, but only at T1 and during VCL treatment.Conclusions: The correlations between DR rate and sleep fragmentation measures underlined that VCL cannot be considered as a direct cause of abnormal dreams. Comparisons between groups cast some doubts on the actual existence of abnormal dreams, at least as compared to the NRT group. Our results are consistent with the 'activation models', showing that numerous DRs in the VCL group may be related to lighter sleep. [ABSTRACT FROM AUTHOR]

To control and to manage the geometric deviations along the product life cycle, the first step is to consider, during the design stage, the tolerance specification, the tolerance allocation and the tolerance analysis. Many approaches of the literature for tolerance analysis of rigid assemblies exist, and different commercial computer-aided tolerancing (CAT) software packages were developed with those models. However, there is a growing interest in considering working conditions and operating windows in CAT. As a response to these needs, skin model concept was proposed. The aim of this paper is to connect a point cloud-based discrete geometry framework (i.e. a skin model representation) to the manufacturing processes, in order to bring the CAT simulation tools closer to reality. In this work, the effect of a manufacturing process on solving a stack-up function is investigated throughout circular profiles obtained by a turning process. A case study has been defined and solved using two literature models, the variational model and the vector-loop one, by considering the manufacturing signature. The results have been compared to those obtained by the same models without considering the manufacturing signature. Monte Carlo simulations have been carried out by solving the stack-up functions into Matlab® software, and statistical analyses have been carried out by Minitab® software. [ABSTRACT FROM AUTHOR]

Consider a rational projective plane curve C parameterized by three homogeneous forms of the same degree in the polynomial ring R = k [ x , y ] over a field k . The ideal I generated by these forms is presented by a homogeneous 3 × 2 matrix φ with column degrees d 1 ≤ d 2 . The Rees algebra R = R [ I t ] of I is the bi-homogeneous coordinate ring of the graph of the parameterization of C ; and accordingly, there is a dictionary that translates between the singularities of C and algebraic properties of the ring R and its defining ideal. Finding the defining equations of Rees rings is a classical problem in elimination theory that amounts to determining the kernel A of the natural map from the symmetric algebra Sym ( I ) onto R . The ideal A ≥ d 2 − 1 , which is an approximation of A , can be obtained using linkage. We exploit the bi-graded structure of Sym ( I ) in order to describe the structure of an improved approximation A ≥ d 1 − 1 when d 1 < d 2 and φ has a generalized zero in its first column. (The latter condition is equivalent to assuming that C has a singularity of multiplicity d 2 .) In particular, we give the bi-degrees of a minimal bi-homogeneous generating set for this ideal. When 2 = d 1 < d 2 and φ has a generalized zero in its first column, then we record explicit generators for A . When d 1 = d 2 , we provide a translation between the bi-degrees of a bi-homogeneous minimal generating set for A d 1 − 2 and the number of singularities of multiplicity d 1 that are on or infinitely near C . We conclude with a table that translates between the bi-degrees of a bi-homogeneous minimal generating set for A and the configuration of singularities of C when the curve C has degree six. [ABSTRACT FROM AUTHOR]

Let R = k [ T 1 , … , T f ] be a standard graded polynomial ring over the field k and Ψ be an f × g matrix of linear forms from R , where 1 ≤ g < f . Assume [ T 1 ⋯ T f ] Ψ is 0 and that grade I g ( Ψ ) is exactly one short of the maximum possible grade. We resolve R ‾ = R / I g ( Ψ ) , prove that R ‾ has a g -linear resolution, record explicit formulas for the h -vector and multiplicity of R ‾ , and prove that if f − g is even, then the ideal I g ( Ψ ) is unmixed. Furthermore, if f − g is odd, then we identify an explicit generating set for the unmixed part, I g ( Ψ ) unm , of I g ( Ψ ) , resolve R / I g ( Ψ ) unm , and record explicit formulas for the h -vector of R / I g ( Ψ ) unm . (The rings R / I g ( Ψ ) and R / I g ( Ψ ) unm automatically have the same multiplicity.) These results have applications to the study of the blow-up algebras associated to linearly presented grade three Gorenstein ideals. [ABSTRACT FROM AUTHOR]

Presents information on a study that investigated the nucleation of diamond from a gas phase in a hot filament assisted chemical vapor deposition. Discussion on the nucleation density in diamond deposition; Background on diamond crystallites.