Integrated Approach of Life Cycle Assessment and Experimental Design in the Study of a Model Organic Reaction: New Perspectives in Renewable Vanillin-Derived Chemicals.

This work is focused on performing a quantitative assessment of the environmental impacts associated with an organic synthesis reaction, optimized using an experimental design approach. A nucleophilic substitution reaction was selected, employing vanillin as the substrate, a phenolic compound widely used in the food industry and of pharmaceutical interest, considering its antioxidant and antitumoral potential. To carry out the reaction, three different solvents have been chosen, namely acetonitrile (ACN), acetone (Ace), and dimethylformamide (DMF). The syntheses were planned with the aid of a multivariate experimental design to estimate the best reaction conditions, which simultaneously allow a high product yield and a reduced environmental impact as computed by Life Cycle Assessment (LCA) methodology. The experimental results highlighted that the reactions carried out in DMF resulted in higher yields with respect to ACN and Ace; these reactions were also the ones with lower environmental impacts. The multilinear regression models allowed us to identify the optimal experimental conditions able to guarantee the highest reaction yields and lowest environmental impacts for the studied reaction. The identified optimal experimental conditions were also validated by experimentally conducting the reaction in those conditions, which indeed led to the highest yield (i.e., 93%) and the lowest environmental impacts among the performed experiments. This work proposes, for the first time, an integrated approach of DoE and LCA applied to an organic reaction with the aim of considering both conventional metrics, such as reaction yield, and unconventional ones, such as environmental impacts, during its lab-scale optimization.

Automatic Multiview Alignment of RGB-D Range Maps of Upper Limb Anatomy.

Digital representations of anatomical parts are crucial for various biomedical applications. This paper presents an automatic alignment procedure for creating accurate 3D models of upper limb anatomy using a low-cost handheld 3D scanner. The goal is to overcome the challenges associated with forearm 3D scanning, such as needing multiple views, stability requirements, and optical undercuts. While bulky and expensive multi-camera systems have been used in previous research, this study explores the feasibility of using multiple consumer RGB-D sensors for scanning human anatomies. The proposed scanner comprises three Intel® RealSenseTM D415 depth cameras assembled on a lightweight circular jig, enabling simultaneous acquisition from three viewpoints. To achieve automatic alignment, the paper introduces a procedure that extracts common key points between acquisitions deriving from different scanner poses. Relevant hand key points are detected using a neural network, which works on the RGB images captured by the depth cameras. A set of forearm key points is meanwhile identified by processing the acquired data through a specifically developed algorithm that seeks the forearm's skeleton line. The alignment process involves automatic, rough 3D alignment and fine registration using an iterative-closest-point (ICP) algorithm expressly developed for this application. The proposed method was tested on forearm scans and compared the results obtained by a manual coarse alignment followed by an ICP algorithm for fine registration using commercial software. Deviations below 5 mm, with a mean value of 1.5 mm, were found. The obtained results are critically discussed and compared with the available implementations of published methods. The results demonstrate significant improvements to the state of the art and the potential of the proposed approach to accelerate the acquisition process and automatically register point clouds from different scanner poses without the intervention of skilled operators. This study contributes to developing effective upper limb rehabilitation frameworks and personalized biomedical applications by addressing these critical challenges.

Management of Asbestos Containing Materials: A Detailed LCA Comparison of Different Scenarios Comprising First Time Asbestos Characterization Factor Proposal.

This work addresses the complex issue of asbestos containing materials (ACMs) management, by focusing on the scenario of six municipalities comprised in the Reggio Emilia province of Emilia Romagna Italian region. Particularly, the life cycle assessment (LCA) methodology was applied in order to assess in a quantitative and reliable manner the human toxicity as well as the ecotoxicity impacts associated with all of the different phases of ACMs management. The latter comprises mapping of ACMs, creation of a risk map for defining priority of intervention, encapsulation and removal of ACMs, as well as the as obtained asbestos containing waste (ACW) end of life. Particularly, a thermal inertisation treatment performed in a continuous industrial furnace was considered as the innovative end of life scenario to be compared with what actually was provided by the legislation of many countries worldwide, that is, the disposal of ACW in a controlled landfill for hazardous wastes. A characterization factor for asbestos fibers released both in outdoor air and in occupational setting was proposed for the first time and included in the USEtox 2.0 impact assessment method. This allowed us to reliably and quantitatively highlight that inertisation treatments should be the preferred solutions to be adopted by local and national authorities, especially if the obtained inert material finds application as secondary raw materials, thus contributing to a decrease in the environmental damage (limited to its toxicological contributions) to be associated with asbestos management.

Automatic Calibration of a Two-Axis Rotary Table for 3D Scanning Purposes.

Rotary tables are often used to speed up the acquisition time during the 3D scanning of complex geometries. In order to avoid manual registration of the point clouds acquired with different orientations, automatic algorithms to compensate the rotation were developed. Alternatively, a proper calibration of the rotary axis with respect to the camera system is needed. Several methods are available in the literature, but they only consider a single-axis calibration. In this paper, a method for the simultaneous calibration of both axes of the table is proposed. A checkerboard is attached to the table, and several images with different poses are acquired. An optimization algorithm is then setup to determine the orientation and the locations of the two axes. A metric to assess the calibration quality was also defined by computing the average mean reprojection error. This metric is used to investigate the optimal number and distribution of the calibration poses, demonstrating that the optimum calibration results are achieved when a wider dispersion of the calibration poses is adopted.

Sensor Architectures and Technologies for Upper Limb 3D Surface Reconstruction: A Review.

3D digital models of the upper limb anatomy represent the starting point for the design process of bespoke devices, such as orthoses and prostheses, which can be modeled on the actual patient's anatomy by using CAD (Computer Aided Design) tools. The ongoing research on optical scanning methodologies has allowed the development of technologies that allow the surface reconstruction of the upper limb anatomy through procedures characterized by minimum discomfort for the patient. However, the 3D optical scanning of upper limbs is a complex task that requires solving problematic aspects, such as the difficulty of keeping the hand in a stable position and the presence of artefacts due to involuntary movements. Scientific literature, indeed, investigated different approaches in this regard by either integrating commercial devices, to create customized sensor architectures, or by developing innovative 3D acquisition techniques. The present work is aimed at presenting an overview of the state of the art of optical technologies and sensor architectures for the surface acquisition of upper limb anatomies. The review analyzes the working principles at the basis of existing devices and proposes a categorization of the approaches based on handling, pre/post-processing effort, and potentialities in real-time scanning. An in-depth analysis of strengths and weaknesses of the approaches proposed by the research community is also provided to give valuable support in selecting the most appropriate solution for the specific application to be addressed.

An Omnidirectional Vision Sensor Based on a Spherical Mirror Catadioptric System.

The combination of mirrors and lenses, which defines a catadioptric sensor, is widely used in the computer vision field. The definition of a catadioptric sensors is based on three main features: hardware setup, projection modelling and calibration process. In this paper, a complete description of these aspects is given for an omnidirectional sensor based on a spherical mirror. The projection model of a catadioptric system can be described by the forward projection task (FP, from 3D scene point to 2D pixel coordinates) and backward projection task (BP, from 2D coordinates to 3D direction of the incident light). The forward projection of non-central catadioptric vision systems, typically obtained by using curved mirrors, is usually modelled by using a central approximation and/or by adopting iterative approaches. In this paper, an analytical closed-form solution to compute both forward and backward projection for a non-central catadioptric system with a spherical mirror is presented. In particular, the forward projection is reduced to a 4th order polynomial by determining the reflection point on the mirror surface through the intersection between a sphere and an ellipse. A matrix format of the implemented models, suitable for fast point clouds handling, is also described. A robust calibration procedure is also proposed and applied to calibrate a catadioptric sensor by determining the mirror radius and center with respect to the camera.

Innovative Bioplasticizers from Residual Cynara cardunculus L. Biomass-Derived Levulinic Acid and Their Environmental Impact Assessment by LCA Methodology.

This work is focused on the application of Life Cycle Assessment (LCA) methodology for the quantification of the potential environmental impacts associated with the obtainment of levulinic acid from residual Cynara cardunculus L. biomass and its subsequent valorization in innovative bioplasticizers for tuning the properties as well as the processability of biopolymers. This potentially allows the production of fully biobased and biodegradable bioplastic formulations, thus addressing the issues related to the fossil origin and nonbiodegradability of conventional additives, such as phthalates. Steam explosion pretreatment was applied to the epigean residue of C. cardunculus L. followed by a microwave-assisted acid-catalyzed hydrolysis. After purification, the as-obtained levulinic acid was used to synthesize different ketal-diester derivatives through a three-step selective synthesis. The levulinic acid-base additives demonstrated remarkable plasticizing efficiency when added to biobased plastics. The LCA results were used in conjunction with those from the experimental activities to find the optimal compromise between environmental impacts and mechanical and thermal properties, induced by the bioadditives in poly(3-hydroxybutyrate), PHB biopolymer.

Life Cycle Impact Assessment of Solution Combustion Synthesis of Titanium Dioxide Nanoparticles and Its Comparison with More Conventional Strategies.

This paper represents the first attempt to quantitatively and reliably assess the environmental sustainability of solution combustion synthesis (SCS) with respect to other soft chemistry strategies, which are more conventionally employed in the preparation of engineered oxide nanomaterials, namely hydrolytic and non-hydrolytic sol-gel syntheses (i. e., HSGS and NHSGS). Indeed, although SCS is well known to rely on significant reduction in the energy as well as time required for the obtainment of the desired nanocrystals, its quantitative environmental assessment and a detailed comparison with other existing synthetic pathways represents an absolute novelty of high scientific desirability in order to pursue a more sustainable development in the inorganic chemistry as well as materials science research fields. TiO2 nanoparticles were selected as the material of choice, for the production of which three slightly modified literature procedures were experimentally reproduced and environmentally evaluated by the application of the comprehensive life cycle assessment (LCA) methodology. Particularly, SCS was compared from an environmental perspective with sol-gel approaches performed both in water and in benzyl alcohol. The results of the present study were also framed among those recently obtained in a systematic study assessing seven further chemical, physical, and biological routes for the synthesis of TiO2 nanoparticles, comprising also flame spray pyrolysis (typically used in industrial productions), highlighting and quantifying the excellent environmental performances of SCS.

Bembidion (Ocydromus) terryerwini sp. nov. from Iran (Coleoptera, Carabidae, Bembidiina).

Bembidion (Ocydromus) terryerwinisp. nov. from Central Iran (Kerman and Yazd Provinces), described here, belongs to the decorum species group (Ocydromus Clairville, 1806). The new species is compared with the other taxa of this species group occurring in Iran and neighboring regions (Georgia, Armenia, Azerbaijan, Turkey, Iraq, Iran, South Pakistan, Afghanistan, and Turkmenistan).

Geographic and taxonomic notes, addenda and corrigenda on the subtribe Bembidiina Stephens, 1827 of the 2017 'Catalogue of Palaearctic Coleoptera' (Coleoptera, Carabidae, Bembidiina).

Some corrections to the section of subtribe Bembidiina of the Catalogue of Palaearctic Coleoptera, Vol. 1, together with geographic, systematic, and synonymic updates are reported and commented upon. The following five new synonymies are proposed (with junior synonym listed first): Bembidion (Peryphanes) dostali Kirschenhofer, 1984 = Bembidion (Peryphanes) sanatum Bates, 1883 syn. nov.; Bembidion (Terminophanes) pseudoconsumatum Kirschenhofer, 1984 = Bembidion (Terminophanes) sjoelanderi Jedlicka, 1965 syn. nov.; Bembidion (Asioperyphus) sapporense Jedlicka, 1951 = Bembidion (Politophanes) chloreum Bates, 1873 syn. nov.; Bembidion (Peryphus) torosiense Jedlicka, 1961 = Bembidion (Peryphus) subcostatum vau Netolitzky, 1913 syn. nov.; Sinechostictus (Sinechostictus) multisulcatus cariniger Korge, 1971 = Sinechostictus (Sinechostictus) multisulcatus (Reitter, 1890) syn. nov. Furthermore we confirm the following synonimies: Asaphidion weiratheri Netolitzky, 1935 = Asaphidion ganglbaueri J.Müller, 1921; Sinechostictus (Sinechostictus) effluviorum (Peyron, 1858) = Sinechostictus (Sinechostictus) tarsicus (Peyron, 1858). The following nine new combinations are proposed: Bembidion (Euperyphus) dimidiatum Ménétriés, 1832 comb. nov.; Bembidion (Peryphus) psuchrum Andrewes, 1922 comb. nov.; Bembidion (Plataphus) pseudolucillum Netolitzky, 1938 comb. nov.; Bembidion (Politophanes) chloreum Bates, 1873 comb. nov.; Bembidion (Politophanes) gotoense Habu, 1973 comb. nov.; Bembidion (Politophanes) shunichii Habu, 1973 comb. nov.; Bembidion (Politophanes) umeyai Habu, 1959 comb. nov.; Bembidion (Politophanes) yoshidai Morita, 2009 comb. nov.; Bembidion (Terminophanes) sjoelanderi Jedlicka, 1965 comb. nov. The species Bembidion psuchrum Andrewes, 1922 and Bembidion sanatum Bates, 1883 are here redescribed.

Semi-Automatic Tool for Vitiligo Detection and Analysis.

Vitiligo vulgaris is an autoimmune disease which causes a strong reduction of the cells producing melanin, which is the main skin pigment. This results in the growth of white patches on patients' skin, which are more or less visible, depending on the skin phototype. Precise, objective and fast detection of vitiligo patches would be crucial to produce statistically relevant data on huge populations, thus giving an insight on the disease. However, few methods are available in literature. In the present paper, a semi-automatic tool based on image processing to detect facial vitiligo patches is described. The tool requires pictures to be captured under black light illumination, which enhances patches contrast with respect to healthy skin. The user is only required to roughly define the regions of interest and set a global threshold, thus, no specific image-processing skills are required. An adaptive algorithm then automatically discerns between vitiligo and healthy skin pixels. The tools also allow for a statistical data interpretation by overlapping the detected patches of all patients on a face template through an occurrence map. Preliminary results obtained on a small population of 15 patients allowed us to assess the tool's performance. Patch detection was checked by an experienced dermatologist, who confirmed the detection for all the studied patients, thus supporting the effectiveness of the proposed tool.

Design and manufacturing of patient-specific orthodontic appliances by computer-aided engineering techniques.

Orthodontic treatments are usually performed using fixed brackets or removable oral appliances, which are traditionally made from alginate impressions and wax registrations. Among removable devices, eruption guidance appliances are used for early orthodontic treatments in order to intercept and prevent malocclusion problems. Commercially available eruption guidance appliances, however, are symmetric devices produced using a few standard sizes. For this reason, they are not able to meet all the specific patient's needs since the actual dental anatomies present various geometries and asymmetric conditions. In this article, a computer-aided design-based methodology for the design and manufacturing of a patient-specific eruption guidance appliances is presented. The proposed approach is based on the digitalization of several steps of the overall process: from the digital reconstruction of patients' anatomies to the manufacturing of customized appliances. A finite element model has been developed to evaluate the temporomandibular joint disks stress level caused by using symmetric eruption guidance appliances with different teeth misalignment conditions. The developed model can then be used to guide the design of a patient-specific appliance with the aim at reducing the patient discomfort. At this purpose, two different customization levels are proposed in order to face both arches and single tooth misalignment issues. A low-cost manufacturing process, based on an additive manufacturing technique, is finally presented and discussed.

Stable peptide inhibitors prevent binding of lethal and oedema factors to protective antigen and neutralize anthrax toxin in vivo.

The lethal and oedema toxins produced by Bacillus anthracis, the aetiological agent of anthrax, are made by association of protective antigen with lethal and oedema factors and play a major role in the pathogenesis of anthrax. In the present paper, we describe the production of peptide-based specific inhibitors in branched form which inhibit the interaction of protective antigen with lethal and oedema factors and neutralize anthrax toxins in vitro and in vivo. Anti-protective antigen peptides were selected from a phage library by competitive panning with lethal factor. Selected 12-mer peptides were synthesized in tetra-branched form and were systematically modified to obtain peptides with higher affinity and inhibitory efficiency.

Environmental and human health assessment of life cycle of nanoTiO2 functionalized porcelain stoneware tile.

Recently, there has been a rise in the interest in nanotechnology due to its enormous potential for the development of new products and applications with higher performance and new functionalities. However, while nanotechnology might revolutionize a number of industrial and consumer sectors, there are uncertainties and knowledge gaps regarding toxicological effects of this emerging science. The goal of this research concerns the implementation into Life Cycle Assessment (LCA) of preliminary frameworks developed to evaluate human toxicity and exposure factors related to the potential nanoparticle releases that could occur during the life cycle steps of a functionalized building material. The present LCA case study examines the ecodesign of nanoTiO2 functionalized porcelain stoneware tile production. The aim of this investigation is to manufacture new eco-friendly products in order to protect human health and ecosystem quality and to offer the market, materials with higher technological properties obtained by the addition of specific nanomaterials.

NMR and MD studies on the interaction between ligand peptides and alpha-bungarotoxin.

The interaction between alpha-bungarotoxin and linear synthetic peptides, mimotope of the nicotinic acetylcholine receptor binding site, has been characterised extensively by several methods and a wealth of functional, kinetic and structural data are available. Hence, this system represents a suitable model to explore in detail the dynamics of a peptide-protein interaction. Here, the solution structure of a new complex of the protein toxin with a tridecapeptide ligand exhibiting high affinity has been determined by NMR. As observed for three other previously reported mimotope-alpha-bungarotoxin complexes, also in this case correlations between biological activity and kinetic data are not fully consistent with a static discussion of structural data. Molecular dynamics simulations of the four mimotope-toxin complexes indicate that a relevant contribution to the complex stability is given by the extent of the residual flexibility that the protein maintains upon peptide binding. This feature, limiting the entropy loss caused by protein folding and binding, ought to be generally considered in a rational design of specific protein ligands.

Rational design and molecular diversity for the construction of anti-alpha-bungarotoxin antidotes with high affinity and in vivo efficiency.

The structure of peptide p6.7, a mimotope of the nicotinic receptor ligand site that binds alpha-bungarotoxin and neutralizes its toxicity, was compared to that of the acetylcholine binding protein. The central loop of p6.7, when complexed with alpha-bungarotoxin, fits the structure of the acetylcholine binding protein (AChBP) ligand site, whereas peptide terminal residues seem to be less involved in toxin binding. The minimal binding sequence of p6.7 was confirmed experimentally by synthesis of progressively deleted peptides. Affinity maturation was then achieved by random addition of residues flanking the minimal binding sequence and by selection of new alpha-bungarotoxin binding peptides on the basis of their dissociation kinetic rate. The tetra-branched forms of the resulting high-affinity peptides were effective as antidotes in vivo at a significantly lower dose than the tetra-branched lead peptide.

Involvement of oxidative stress in apoptosis induced by a mixture of isothiazolinones in normal human keratinocytes.

A 3:1 combination of 5-chloro-2-methyl-4-isothiazolin-3-one (CMI) and 2-methyl-4-isothiazolin-3-one (MI) is widely used to preserve cosmetic products. We show here that CMI/MI induced apoptosis in normal human keratinocytes (NHK) as at low concentrations (0.001-0.05% documented by subdiploid DNA content and phosphatidylserine exposure, while at the highest concentration (0.1% as supplied, 15 p.p.m.) the response was necrosis. Various molecular events accompanied the cytotoxic effects of CMI/MI. Generation of ROS and hyperpolarization of mitochondrial transmembrane potential (DeltaPsim) were early events, followed by increased Fas expression and activation of caspase-8, and then activation of caspase-3 and -9. The drop in DeltaPsim occurred only later in the cell death pathway, when NHK showed signs of apoptosis. Pretreatment of cells for 2 h with the redox-active agent N-acetyl-L-cysteine conferred complete protection against the CMI/MI-induced cytotoxic effects, DeltaPsim loss, and apoptosis. The pan-caspase inhibitor Z-Val-Ala-Asp(OMe)-CH2F blocked the CMI/MI-induced apoptosis without preventing ROS generation and the drop in DeltaPsim. These results indicate that the generation of ROS plays an important part in mediating apoptosis and necrosis associated with CMI/MI treatment. This new aspect of the in vitro toxicity of CMI/MI may provide important information about the relationship between the preservative's in vitro apoptotic activity and its in vivo toxicity.

In vitro induction of apoptosis vs. necrosis by widely used preservatives: 2-phenoxyethanol, a mixture of isothiazolinones, imidazolidinyl urea and 1,2-pentanediol.

Preservatives are added to many final products, such as detergents, cosmetics, pharmaceuticals and vaccines. We conducted an in vitro investigation of the apoptosis- and necrosis-inducing potential of brief applications (10 min) of four common preservatives: ethylene glycol monophenyl ether, 2-phenoxyethanol (EGPE), imidazolidinyl urea (IMU), a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one (CMI/MI), and 1,2-pentanediol, a "preservative-non-preservative" best known as pentylene glycol. Using HL60 cells, we monitored the kinetics of cell toxicity with the MTT test and analysed extranuclear end points of apoptosis, i.e. phosphatidylserine exposure and nuclear fragmentation. Preservative treatment resulted in a dose-dependent decrease of cell viability. The mode of cell death was dose-dependent: necrosis occurred at high concentrations while apoptosis, shown by DNA laddering, DNA sub-diploid peak and caspase-3 activation, occurred at lower concentrations 0-24hr after exposure to a single dose: CMI/MI induced apoptosis at low concentrations (0.001-0.01%) and necrosis at high concentrations (0.5-0.1%); IMU and EGPE required higher concentrations to induce apoptosis (IMU 0.01-0.1% and EGPE 0.01-0.5%) or necrosis (IMU 0.5-1% and EGPE only at 1%). PG induced apoptosis only at 5%. Externalization of PS, a hallmark of apoptosis, occurred early in HL60 treated with low concentrations of CMI/MI and EGPE and was concomitant with the subdiploid peak in HL60 treated with PG. However, it did not occur in HL60 treated with IMU. In conclusion, at appropriate concentrations, each of the four preservatives modulates the apoptotic machinery by a caspase-dependent mechanism. Thus, apoptosis could be a good parameter to evaluate the cytoxicity of these chemical compounds.

Selective occlusion of tumor blood vessels by targeted delivery of an antibody-photosensitizer conjugate.

The irregular vasculature and high interstitial pressure of solid tumors hinder the delivery of cytotoxic agents to cancer cells. As a consequence, the doses of chemotherapy necessary to achieve complete tumor eradication are associated with unacceptably high toxicities. The selective thrombosis of tumor blood vessels has been postulated as an alternative avenue for combating cancer, depriving tumors of nutrients and oxygen and causing an avalanche of tumor cell deaths. The human antibody L19, specific to the EDB domain of fibronectin, a marker of angiogenesis, is capable of selective in vivo localization around tumor blood vessels and is thus a suitable agent for delivering toxic payloads to the tumor neovasculature. Here we show that a chemical conjugate of the L19 antibody with the photosensitizer bis(triethanolamine)Sn(IV) chlorin e(6), after intravenous injection and irradiation with red light, caused an arrest of tumor growth in mice with subcutaneous tumors. By contrast, a photosensitizer conjugate obtained with an antibody of identical pharmacokinetic properties but irrelevant specificity did not exhibit a significant therapeutic effect. These results confirm that vascular targeting strategies, aimed at the selective occlusion/disruption of tumor blood vessels, have a significant anticancer therapeutic potential and encourage the use of antibody-photosensitizer conjugates for the therapy of superficial tumors and possibly other angiogenesis-related pathologies.

Antimicrobial activity of novel dendrimeric peptides obtained by phage display selection and rational modification.

A large 10-mer phage peptide library was panned against whole Escherichia coli cells, and an antimicrobial peptide (QEKIRVRLSA) was selected. The peptide was synthesized in monomeric and dendrimeric tetrabranched form (multiple antigen peptide [MAP]), which generally allows a dramatic increase of peptide stability to peptidases and proteases. The antibacterial activity of the dendrimeric peptide against E. coli was much higher than that of the monomeric form. Modification of the original sequence, by residue substitution or sequence shortening, produced three different MAPs, M4 (QAKIRVRLSA), M5 (KIRVRLSA), and M6 (QKKIRVRLSA) with enhanced stability to natural degradation and antimicrobial activity against a large panel of gram-negative bacteria. The MICs of the most potent peptide, M6, were as low as 4 to 8 microg/ml against recent clinical isolates of multidrug-resistant Pseudomonas aeruginosa and members of the Enterobacteriaceae. The same dendrimeric peptides showed high stability to blood proteases, low hemolytic activity, and low cytotoxic effects on eukaryotic cells, making them promising candidates for the development of new antibacterial drugs.