PEPTIDE-POLYMER CONJUGATES AS TOOLS TO SELECTIVELY TARGET EGFR

Nanoparticles (NPs) made of biodegradable and biocompatible polymers present several advantages as carriers for therapeutics. Targeted polymeric NPs, able to hit specific tissues and cells, can be obtained by synthesis of hybrid or biointegrated nanosystems where the combination of polymers with biomolecules such as peptides, proteins, or monoclonal antibodies offers opportunities to design precise and versatile nanoscale systems. The central challenge towards these \u201csmart\u201d materials is represented by the optimal interplay of biophysicochemical parameters that confer molecular targeting, immune evasion, and optimal drug release, and allow to overcome the physiological barriers in vivo. The epidermal growth factor receptor (EGFR) is a cell-surface receptor of extracellular protein ligands of the epidermal growth factor family. Mutations that lead to EGFR overexpression or overactivity have been associated with a wide spectrum of human cancers of epithelial origin, including breast and colorectal cancers, and with autoimmune disorders like rheumatoid arthritis. Recently, several studies have reported the successful identification, by screening phage display libraries, of a peptide ligand, named GE11 (YHWYGYTPQNVI), with high binding capacity to EGFR but with low mitogenic activity. Poly(gamma-glutamic acid) (gamma-PGA) is an extracellular bacterial water-soluble polymer with variable molecular weight produced by several members of the genus Bacillus, composed of D and/or L-glutamic acid monomers, connected by amide bonds between alpha-amino and gamma-carboxyl groups. gamma-PGA is readily biodegraded by a good number of bacteria, it is non-immunogenic and completely innocuous and so it seems to meet most of the requirements of polymers for drug delivery. In addition, it bears pendant carboxylic groups in \u3b1-position which are available for chemical derivatization allowing the modification of its molecular properties or the attachment of biologically active molecules. The use of gamma-PGA, however, presents some inherent and not negligible issues. First of all, chemical modification of the material is very arduous: this is a consequence of its structure but also of its scarce solubility in most organic solvents. Consequently, studies are necessar to find a feasible and efficient way to exploit it for drug delivery purposes. This PhD work aimed to find a way to valorize gamma-PGA peculiar characteristics in drug delivery field, particularly in the preparation of GE11 directed nanocarriers. We operated on two different sides: on one hand we performed intense studies on the biopolymer exploring its chemical-physical properties (mainly MW and solubility), its structure and its reactivity. On the other hand we studied and optimized methods to functionalize a well known and widely used biopolymer, poly lactic-co-glycolic acid (PLGA), with peptides. Starting from these conjugates we also prepared and characterized nanoparticles intended to be used as a drug delivery tools to EGFR overexpressing cells

Online Motion Planning for Safe Human–Robot Cooperation Using B-Splines and Hidden Markov Models

When humans and robots work together, ensuring safe cooperation must be a priority. This research aims to develop a novel real-time planning algorithm that can handle unpredictable human movements by both slowing down task execution and modifying the robot’s path based on the proximity of the human operator. To achieve this, an efficient method for updating the robot’s motion is developed using a two-fold control approach that combines B-splines and hidden Markov models. This allows the algorithm to adapt to a changing environment and avoid collisions. The proposed framework is thus validated using the Franka Emika Panda robot in a simple start–goal task. Our algorithm successfully avoids collision with the moving hand of an operator monitored by a fixed camera

Integration of robotic systems in a packaging machine: A tool for design and simulation of efficient motion trajectories

In this paper, the advantages of CACSD (Computer Aided Control System Design) tools for integrating a robotic system in a packaging machine are illustrated. Beside the mechanical integration of the robot into the machine architecture, it is necessary a functional integration, that requires a precise synchronization with the other parts of the system. In the proposed application, a robot with a parallel kinematics is used for pick-and-place tasks between two conveyor belts. It is therefore necessary a proper motion planning which allows to synchronize the grasp and release phases with the conveyor belts, avoiding obstacles and guaranteeing the compliance with bounds on velocity, acceleration and limits in the workspace. A trajectory composed by quintic polynomials has been considered and a specific tool has been designed in the Matlab environment, which allows to modify the parameters of the trajectory and to analyze the obtained motion profiles from both the kinematic and dynamic point of view

Chemistry of α-mangostin : studies on the semisynthesis of minor xanthones from Garcinia mangostana

\u3b1-Mangostin is the major prenylated xanthone from Garcinia mangostana and it has been used also in recent times as starting material for the semisynthetic preparation of various biologically active derivatives. Its structure is characterised by the presence of few functional groups amenable to chemical manipulations, but present in the molecule in multiple instances (three phenolic hydroxyl groups, two prenyl chains and two unsubstituted aromatic carbons). This study represents a first approach to the systematic investigation of the reactivity of \u3b1-mangostin and describes the semisynthesis of some minor xanthones isolated from G. mangostana

Unravelling the ultrafast dynamics of a N-BODIPY compound

Although the photophysics of BODIPY compounds has been widely investigated in the last few years, their analogues N-BODIPY, with nitrogen substitution at the boron center, did not receive comparable attention. In this work we report the synthesis and photochemical characterization of a substituted N-BODIPY compound, by means of a combined theoretical and spectroscopic approach. Compared to a standard BODIPY, the compound under investigation presents a lower fluorescence quantum yield (QY) in the visible region. The excited state relaxation dynamics of the dye was studied in different solvents, showing further fluorescence quenching in polar solvents, and excited state decay rates strongly dependent on the environment polarity. The role of the pendant moieties and the involvement of charge transfer states in the excited state dynamics was experimentally addressed by transient absorption spectroscopy, and further analyzed with TD-DFT calculations, which allowed precise assignment of the transient signals to the correspondent electronic configuration. The complete picture of the N-BODIPY behavior shows the presence of both charge transfer and localized states, influencing the observed photophysics to different amounts, depending on the excitation conditions and the surrounding environment

Proteomics-based investigation in C2C12 myoblast differentiation

Skeletal muscle cell differentiation is a multistage process extensively studied over the years. Even if great improvements have been achieved in defining biological process underlying myogenesis, many molecular mechanisms need still to be clarified

Acoustic correction factor estimate for compensating vertical diel migration of small pelagics

Differences in acoustic estimates of small pelagic fish biomass, due to data acquisition during daytime and nighttime surveys, have been recognized for many years as a problem in acoustic surveys. In the absence of a single rule for all species and for all locations, some expert groups identified specific time intervals for acoustic data acquisition in relation to the schooling behavior of the target species. In the Mediterranean Sea, the research groups working in the MEDIAS (Mediterranean International Acoustic Survey) agreed on the importance that acoustic sampling are conducted only during day-time. Only when available time does not permit to complete the survey during daytime, data collection might be extended. In this case, working on data collected during both daytime and nighttime, a bias may occur in the biomass estimates. In order to evaluate and correct such bias, specific experiments were performed in some geographical sub-areas of the Mediterranean Sea. The data analysis allowed the estimation of a mean correction factor for the Strait of Sicily, where five surveys were carried out in different years. The correction factor was estimated also for the Adriatic Sea, Tyrrhenian Sea and Northern Spain; the observed variability among areas highlighted the importance of the spatial and temporal coverage of the survey area in order to obtain reliable estimates of the correction factor. Further studies are necessary to improve the interpretation of the obtained estimates in relation to area-related peculiarities such as zooplankton composition and abundance along with small pelagic fish community structure

Principal components analysis based control of a multi-dof underactuated prosthetic hand

<p>Abstract</p> <p>Background</p> <p>Functionality, controllability and cosmetics are the key issues to be addressed in order to accomplish a successful functional substitution of the human hand by means of a prosthesis. Not only the prosthesis should duplicate the human hand in shape, functionality, sensorization, perception and sense of body-belonging, but it should also be controlled as the natural one, in the most intuitive and undemanding way. At present, prosthetic hands are controlled by means of non-invasive interfaces based on electromyography (EMG). Driving a multi degrees of freedom (DoF) hand for achieving hand dexterity implies to selectively modulate many different EMG signals in order to make each joint move independently, and this could require significant cognitive effort to the user.</p> <p>Methods</p> <p>A Principal Components Analysis (PCA) based algorithm is used to drive a 16 DoFs underactuated prosthetic hand prototype (called CyberHand) with a two dimensional control input, in order to perform the three prehensile forms mostly used in Activities of Daily Living (ADLs). Such Principal Components set has been derived directly from the artificial hand by collecting its sensory data while performing 50 different grasps, and subsequently used for control.</p> <p>Results</p> <p>Trials have shown that two independent input signals can be successfully used to control the posture of a real robotic hand and that correct grasps (in terms of involved fingers, stability and posture) may be achieved.</p> <p>Conclusions</p> <p>This work demonstrates the effectiveness of a bio-inspired system successfully conjugating the advantages of an underactuated, anthropomorphic hand with a PCA-based control strategy, and opens up promising possibilities for the development of an intuitively controllable hand prosthesis.</p