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Abstract: Glycerol is an effective carbon source for the production of scl- and mcl-polyhydroxyalkanoates (PHAs) by Pseudomonas spp. P. mediterranea 9.1 (CFBP 5447) synthesizes an amorphous mcl-PHA when grown on crude glycerol, whereas on both reagent grade (RG) and partially refined (PR) glycerol, it produces two very similar distinctive mcl-PHAs with the unusual property of producing, with the appropriate treatment, a transparent film. Mcl-PHAs recovered after biomass extraction have an average molecular weight of approximately 56,000/63,000Da. The monomer composition and physicochemical properties of such mcl-PHAs suggest their potential application as a softener of biopolymeric blends for food packaging and medical devices. [Copyright &y& Elsevier]

Abstract: In the last decades the Lattice Boltzmann method (LB) has been successfully used to simulate a variety of processes. The LB model describes the microscopic processes occurring at the cellular level and the macroscopic processes occurring at the continuum level with a unique function, the probability distribution function. Recently, it has been tried to couple deterministic approaches with probabilistic cellular automata (probabilistic CA) methods with the aim to model temporal evolution of tumor growths and three dimensional spatial evolution, obtaining hybrid methodologies. Despite the good results attained by CA-PDE methods, there is one important issue which has not been completely solved: the intrinsic stochastic nature of the interactions at the interface between cellular (microscopic) and continuum (macroscopic) level. CA methods are able to cope with the stochastic phenomena because of their probabilistic nature, while PDE methods are fully deterministic. Even if the coupling is mathematically correct, there could be important statistical effects that could be missed by the PDE approach. For such a reason, to be able to develop and manage a model that takes into account all these three level of complexity (cellular, molecular and continuum), we believe that PDE should be replaced with a statistic and stochastic model based on the numerical discretization of the Boltzmann equation: The Lattice Boltzmann (LB) method. In this work we introduce a new hybrid method to simulate tumor growth and immune system, by applying Cellular Automata Lattice Boltzmann (CA-LB) approach. [Copyright &y& Elsevier]

Abstract: Vaccines represent a special class of drugs, capable of stimulating immune system responses against pathogens and tumors. Vaccine development is a lengthy process that includes expensive laboratory experiments in order to assess safety and effectiveness. As the efficacy of a vaccine was demonstrated by biological/chemical investigations and pre-clinical studies, then a major problem is represented by the search for an optimal vaccination dosage. Optimality here assumes the meaning of assuring a high degree of efficacy and safety (lack of toxic or side effects). In lack of quantitative methods, this is usually achieved by a consensus technique, a public statement on a particular aspect of medical knowledge available at the time it was written, and that is generally agreed upon as the evidence-based, state-of-the-art (or state-of-science) knowledge by a representative group of experts in that area. In this article, we focus on the difficult problem of the search for an optimal vaccination dosage in the field of tumor immunology, that is a major issue in biomedical research. This, indeed, represents a first step toward a personalized medicine approach. [Copyright &y& Elsevier]

Abstract: Many physical or biological phenomena deal with the dynamics of interacting entities. These class of phenomena are well described in physics, using a kinetic approach based on Boltzmann equation. A Generalized Kinetic theory has been proposed to extend this approach to biological scenarios. An analytical solution of Boltzmann equation can be found only in very simple cases, so numerical methods become extremely relevant. The particle method is a class of numerical methods used to find a numerical solution of Boltzmann equations. The MWF-method for kinetic equations was firstly proposed by S. Motta and J. Wick in 1992. Here, we show that the MWF-method can be extended to system of Boltzamm equations. [Copyright &y& Elsevier]

[Display omitted] Pharmaceutical nanotechnology research is focused on smart nano-vehicles, which can deliver active pharmaceutical ingredients to enhance their efficacy through any route of administration and in the most varied therapeutical application. The design and development of new nanopharmaceuticals can be very laborious. In recent years, the application of mathematics, statistics and computational tools is emerging as a convenient strategy for this purpose. The application of Quality by Design (QbD) tools has been introduced to guarantee quality for pharmaceutical products and improve translational research from the laboratory bench into applicable therapeutics. In this review, a collection of basic-concept, historical overview and application of QbD in nanomedicine are discussed. A specific focus has been put on Response Surface Methodology and Artificial Neural Network approaches in general terms and their application in the development of nanomedicine to monitor the process parameters obtaining optimized system ensuring its quality profile. [ABSTRACT FROM AUTHOR]

Abstract The pivotal role of the stereocenter at the N -substituent of the 6,7-benzomorphan scaffold was investigated combining synthetic and pharmacological approaches. 2 R - and 2 S -diastereoisomers of the multitarget MOR/DOR antinociceptive ligand LP2 (1) were synthesized and their pharmacological profile was evaluated in in vitro and vivo assays. From our results, 2 S -LP2 (5) showed an improved pharmacological profile in comparison to LP2 (1) and 2 R -LP2 (4). 2 S -LP2 (5) elicited an antinociceptive effect with a 1.5- and 3-times higher potency than LP2 (1) and R -antipode (4), respectively. In vivo effect of 2 S -LP2 (5) was consistent with the improved MOR/DOR efficacy profile assessed by radioligand binding assay, to evaluate the opioid receptor affinity, and BRET assay, to evaluate the capability to promote receptor/G-protein and receptor/β-arrestin 2 interaction. 2 S -LP2 (5) was able to activate, with different efficacy, G-protein pathway over β-arrestin 2, behaving as biased agonist at MOR and mainly at DOR. Considering the therapeutic potential of both multitarget MOR/DOR agonism and functional selectivity over G-protein, the 2 S -LP2 (5) biased multitarget MOR/DOR agonist could provide a safer treatment opportunity. Graphical abstract Image 1 Highligthts • The stereocenter role at the N -substituent of the 6,7-benzomorphan scaffold was investigated. • 2 R - and 2 S -diastereoisomers of the multitarget opioid ligand LP2 were synthesized. • 2 S -LP2 showed a better pharmacological profile than 2 R -LP2 in in vitro and in vivo assays. • 2 S -LP2 resulted a biased multitarget MOR/DOR agonist. • 2 S -LP2 elicited an antinociceptive potency 1.5- and 3-times higher than LP2 and R -antipode. [ABSTRACT FROM AUTHOR]

Reliability assessment of industrial processes is traditionally performed with RAMS techniques. Such techniques are static in nature because they are unable to consider the multi-state operational and failure nature of systems and the dynamic variations of the environment in which they operate. Stochastic Hybrid Automaton appears to overcome this weakness coupling a deterministic and a stochastic process and integrating the features of a dynamic system with the concepts of dynamic reliability. At the state of the art, no attempts to enhance a formal RAMS technique with dynamic reliability has been tried, nor a computer-aided tool that plays as expert system has been coded yet. The aim of this paper is to fill this gap with a simulation formalism and a modelling tool able to combine the Dynamic Fault Tree technique and the Stochastic Hybrid Automaton within the Simulink environment. To this aim the MatCarloRE toolbox was adapted to interact with a Simulink dynamic system. The resulting assembly represents an important step ahead for the delivering of a user-friendly computer-aided tool for the dynamic reliability. [ABSTRACT FROM AUTHOR]

Multiple sclerosis is a disease of the central nervous system that involves the destruction of the insulating sheath of axons, causing severe disabilities. Since the etiology of the disease is not yet fully understood, the use of novel techniques that may help to understand the disease, to suggest potential therapies and to test the effects of candidate treatments is highly advisable. To this end we developed an agent based model that demonstrated its ability to reproduce the typical oscillatory behavior observed in the most common form of multiple sclerosis, relapsing–remitting multiple sclerosis. The model has then been used to test the potential beneficial effects of vitamin D over the disease. Many scientific studies underlined the importance of the blood–brain barrier and of the mechanisms that influence its permeability on the development of the disease. In the present paper we further extend our previously developed model with a mechanism that mimics the blood–brain barrier behavior. The goal of our work is to suggest the best strategies to follow for developing new potential treatments that intervene in the blood–brain barrier. Results suggest that the best treatments should potentially prevent the opening of the blood–brain barrier, as treatments that help in recovering the blood–brain barrier functionality could be less effective. [ABSTRACT FROM AUTHOR]

• An experimental study on two new stress sensors for static SHM of new masonry has been carried out; • Ceramic piezoelectric and capacitive sensors were installed in masonry walls and tested in compression; • The proposed stress sensors are low-cost and of easy installation within mortar joints; • Stress measures by sensors were compared with machine load cell measures to test their reliability; • Results showed good accuracy of sensors, validating their possible use for static SHM of new masonries. Many historical cities enjoy the presence of masonry buildings with inestimable historical, artistic and cultural value. Old masonry buildings often suffer structural deficiencies, design faults and materials aging process. In recent years, many researchers focused their attention on the opportunities that structural health monitoring (SHM) can ensure for the health state of existing masonry structures, where damage can be difficult to be promptly predicted, pontentially causing abrupt collapses, with high risks for the community. This paper presents an experimental study on the effectiveness of two types of stress sensor for SHM of new masonry elements. Ceramic piezoelectric sensors and capacitive sensors were installed in mortar joints of two series of specimens made of calcarenite stone masonry and clay brick masonry. All specimens were tested under uniaxial compression with displacement control, to assess the effectiveness of sensors in recording pressure variation within the different types of masonry and therefore testing their potential use for SHM applications. Even though both the ceramic and capacitive sensors were designed as stress sensors for concrete structures, their installation within mortar joints provided a good response, based on the comparison with standard measurement devices. Results demonstrate the suitability of the sensors even for SHM of masonry structures. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells are the focus of intense research in bone development and regeneration. The potential of microparticles as modulating moieties of osteogenic response by utilizing their architectural features is demonstrated herein. Topographically textured microparticles of varying microscale features are produced by exploiting phase-separation of a readily soluble sacrificial component from polylactic acid. The influence of varying topographical features on primary human mesenchymal stem cell attachment, proliferation and markers of osteogenesis is investigated. In the absence of osteoinductive supplements, cells cultured on textured microparticles exhibit notably increased expression of osteogenic markers relative to conventional smooth microparticles. They also exhibit varying morphological, attachment and proliferation responses. Significantly altered gene expression and metabolic profiles are observed, with varying histological characteristics in vivo. This study highlights how tailoring topographical design offers cell-instructive 3D microenvironments which allow manipulation of stem cell fate by eliciting the desired downstream response without use of exogenous osteoinductive factors. Image 1 • Tailoring topographical patterning of microparticles drives hMSCs differentiation. • Cell adhesion is mediated by different integrins on varied topographical designs. • Altered metabolic profiles of hMSCs on dimpled versus smooth microparticles. • Varying histological features observed in vivo by different 3D surface topographies. [ABSTRACT FROM AUTHOR]