Topological Navigation for Autonomous Underwater Vehicles in Confined Semi-Structured Environments.

In this work, we present the design, implementation, and simulation of a topology-based navigation system for the UX-series robots, a spherical underwater vehicle designed to explore and map flooded underground mines. The objective of the robot is to navigate autonomously in the 3D network of tunnels of a semi-structured but unknown environment in order to gather geoscientific data. We start from the assumption that a topological map has been generated by a low-level perception and SLAM module in the form of a labeled graph. However, the map is subject to uncertainties and reconstruction errors that the navigation system must address. First, a distance metric is defined to compute node-matching operations. This metric is then used to enable the robot to find its position on the map and navigate it. To assess the effectiveness of the proposed approach, extensive simulations have been carried out with different randomly generated topologies and various noise rates.

Bioactive Compounds and Their Impact on Protein Modification in Human Cells.

Reactive oxygen species (ROS) represent a group of molecules with a signaling role that are involved in regulating human cell proliferation and differentiation. Increased ROS concentrations are often associated with the local nonspecific oxidation of biological macromolecules, especially proteins and lipids. Free radicals, in general, may randomly damage protein molecules through the formation of protein-centered radicals as intermediates that, in turn, decay into several end oxidation products. Malondialdehyde (MDA), a marker of free-radical-mediated lipid oxidation and cell membrane damage, forms adducts with proteins in a nonspecific manner, leading to the loss of their function. In our study, we utilized U-937 cells as a model system to unveil the effect of four selected bioactive compounds (chlorogenic acid, oleuropein, tomatine, and tyrosol) to reduce oxidative stress associated with adduct formation in differentiating cells. The purity of the compounds under study was confirmed by an HPLC analysis. The cellular integrity and changes in the morphology of differentiated U-937 cells were confirmed with confocal microscopy, and no significant toxicity was found in the presence of bioactive compounds. From the Western blot analysis, a reduction in the MDA adduct formation was observed in cells treated with compounds that underlaid the beneficial effects of the compounds tested.

Nonlinear Control Strategies for an Autonomous Wing-In-Ground-Effect Vehicle.

Autonomous vehicles are nowadays one of the most important technologies that will be incorporated to every day life in the next few years. One of the most promising kind of vehicles in terms of efficiency and sustainability are those known as Wing-in-Ground crafts, or WIG crafts, a family of vehicles that seize the proximity of ground to achieve a flight with low drag and high lift. However, this kind of crafts lacks of a sound theory of flight that can lead to robust control solutions that guarantees safe autonomous operation in all the cruising phases.In this paper we address the problem of controlling a WIG craft in different scenarios and using different control strategies in order to compare their performance. The tested scenarios include obstacle avoidance by fly over and recovering from a random disturbance in vehicle attitude. MPC (Model Predictive Control) is tested on the complete nonlinear model, while PID, used as baseline controller, LQR (Linear Quadratic Regulator) and adaptive LQR are tested on top of a partial feedback linearization. Results show that LQR has got the best overall performance, although it is seen that different design specifications could lead to the selection of one controller or another.

Functional Self-Awareness and Metacontrol for Underwater Robot Autonomy.

Autonomous systems are expected to maintain a dependable operation without human intervention. They are intended to fulfill the mission for which they were deployed, properly handling the disturbances that may affect them. Underwater robots, such as the UX-1 mine explorer developed in the UNEXMIN project, are paradigmatic examples of this need. Underwater robots are affected by both external and internal disturbances that hamper their capability for autonomous operation. Long-term autonomy requires not only the capability of perceiving and properly acting in open environments but also a sufficient degree of robustness and resilience so as to maintain and recover the operational functionality of the system when disturbed by unexpected events. In this article, we analyze the operational conditions for autonomous underwater robots with a special emphasis on the UX-1 miner explorer. We then describe a knowledge-based self-awareness and metacontrol subsystem that enables the autonomous reconfiguration of the robot subsystems to keep mission-oriented capability. This resilience augmenting solution is based on the deep modeling of the functional architecture of the autonomous robot in combination with ontological reasoning to allow self-diagnosis and reconfiguration during operation. This mechanism can transparently use robot functional redundancy to ensure mission satisfaction, even in the presence of faults.

Combined Experimental and Multivariate Model Approaches for Glycoalkaloid Quantification in Tomatoes.

The intake of tomato glycoalkaloids can exert beneficial effects on human health. For this reason, methods for a rapid quantification of these compounds are required. Most of the methods for α-tomatine and dehydrotomatine quantification are based on chromatographic techniques. However, these techniques require complex and time-consuming sample pre-treatments. In this work, HPLC-ESI-QqQ-MS/MS was used as reference method. Subsequently, multiple linear regression (MLR) and partial least squares regression (PLSR) were employed to create two calibration models for the prediction of the tomatine content from thermogravimetric (TGA) and attenuated total reflectance (ATR) infrared spectroscopy (IR) analyses. These two fast techniques were proven to be suitable and effective in alkaloid quantification (R2 = 0.998 and 0.840, respectively), achieving low errors (0.11 and 0.27%, respectively) with the reference technique.

Varietal and Geographical Origin Characterization of Peaches and Nectarines by Combining Analytical Techniques and Statistical Approach.

Prunus persica L. is one of the most important fruit crops in European production, after grapes, apples, oranges and watermelons. Most varieties are rich in secondary metabolites, showing antioxidant properties for human health. The purpose of this study was to develop a chemical analysis methodology, which involves the use of different analytical-instrumental techniques to deepen the knowledge related to the profile of metabolites present in selected cultivars of peaches and nectarines cultivated in the Mediterranean area (Southern Italy). The comparative study was conducted by choosing yellow-fleshed peaches (RomeStar, ZeeLady) and yellow-fleshed nectarines (Nectaross, Venus) from two geographical areas (Piana di Sibari and Piana di Metaponto), and by determining the chemical parameters for the flesh and skin that allow for identification of any distinctive varietal and/or geographical characteristics. A combined analytical and chemometric approach was used, trough rheological, thermogravimetric (TGA), chromatographic (HPLC-ESI-MS), spectroscopic (UV-Vis, ATR-FTIR, NMR) and spectrometric (ToF-SIMS) analysis. This approach allowed us to identify the characterizing parameters for the analysis of a plant matrix so that the developed methodology could define an easily exportable and extendable model for the characterization of other types of vegetable matrices.

Guidance for Autonomous Underwater Vehicles in Confined Semistructured Environments.

In this work, we present the design, implementation, and testing of a guidance system for the UX-1 robot, a novel spherical underwater vehicle designed to explore and map flooded underground mines. For this purpose, it needs to navigate completely autonomously, as no communications are possible, in the 3D networks of tunnels of semistructured but unknown environments and gather various geoscientific data. First, the overall design concepts of the robot are presented. Then, the guidance system and its subsystems are explained. Finally, the system's validation and integration with the rest of the UX-1 robot systems are presented. A series of experimental tests following the software-in-the-loop and the hardware-in-the-loop paradigms have been carried out, designed to simulate as closely as possible navigation in mine tunnel environments. The results obtained in these tests demonstrate the effectiveness of the guidance system and its proper integration with the rest of the systems of the robot, and validate the abilities of the UX-1 platform to perform complex missions in flooded mine environments.

Tomatine Displays Antitumor Potential in In Vitro Models of Metastatic Melanoma.

There is a growing interest in the cytotoxic effects of bioactive glycoalkaloids, such as α-tomatine on tumor cells. Here, for the first time, we determine the antitumor potential of tomatine, a mixture of α-tomatine and dehydrotomatine, in metastatic melanoma (MM) cell lines harboring different BRAF and MC1R variants. We performed cytotoxicity experiments and annexin-V/propidium iodide staining to assess the apoptotic/necrotic status of the cells. ER stress and autophagy markers were revealed by Western Blot, whereas antiangiogenic and vascular-disrupting effects were evaluated through a capillary tube formation assay on matrigel and by ELISA kit for VEGF release determination. Cell invasion was determined by a Boyden chamber matrigel assay. Tomatine reduced 50% of cell viability and induced a concentration-dependent increase of apoptotic cells in the range of 0.5-1 µM in terms of α-tomatine. The extent of apoptosis was more than two-fold higher in V600BRAF-D184H/D184H MC1R cells than in BRAF wild-type cells and V600BRAF-MC1R wild-type cell lines. Additionally, tomatine increased the LC3I/II autophagy marker, p-eIF2α, and p-Erk1/2 levels in BRAF wild-type cells. Notably, tomatine strongly reduced cell invasion and melanoma-dependent angiogenesis by reducing VEGF release and tumor-stimulating effects on capillary tube formation. Collectively, our findings support tomatine as a potential antitumor agent in MM.

Chemical Characterisation and Antihypertensive Effects of Locular Gel and Serum of Lycopersicum esculentum L. var. "Camone" Tomato in Spontaneously Hypertensive Rats.

Blood pressure control in hypertensive subjects calls for changes in lifestyle, especially diet. Tomato is widely consumed and rich in healthy components (i.e., carotenoids, vitamins and polyphenols). The aim of this study was to evaluate the chemical composition and antihypertensive effects of locular gel reconstituted in serum of green tomatoes of "Camone" variety. Tomato serum and locular gel were chemically characterised. The antihypertensive effects of the locular gel in serum, pure tomatine, and captopril, administered by oral gavage, were investigated for 4 weeks in male spontaneously hypertensive and normotensive rats. Systolic blood pressure and heart rate were monitored using the tail cuff method. Body and heart weight, serum glucose, triglycerides and inflammatory cytokines, aorta thickness and liver metabolising activity were also assessed. Locular gel and serum showed good tomatine and polyphenols content. Significant reductions in blood pressure and heart rate, as well as in inflammatory blood cytokines and aorta thickness, were observed in spontaneously hypertensive rats treated both with locular gel in serum and captopril. No significant effects were observed in normotensive rats. Green tomatoes locular gel and serum, usually discarded during tomato industrial processing, are rich in bioactive compounds (i.e., chlorogenic acid, caffeic acid and rutin, as well as the glycoalkaloids, α-tomatine and dehydrotomatine) that can lower in vivo blood pressure towards healthier values, as observed in spontaneously hypertensive rats.

Secretory IgA-mediated immune response in saliva and early detection of Pseudomonas aeruginosa in the lower airways of pediatric cystic fibrosis patients.

Pseudomonas aeruginosa (Pa) detection in the paranasal sinuses may help to prevent or postpone bacterial aspiration to the lower airways (LAW) and chronic lung infection in cystic fibrosis (CF). We assessed the ability of an ELISA test for measurement of specific Pa secretory IgA (sIgA) in saliva (a potential marker of sinus colonization) to early detect changes in the Pa LAW status (indicated by microbiological sputum or cough swab culture and specific serum IgG levels) of 65 patients for three years, in different investigation scenarios. Increased sIgA levels were detected in saliva up to 22 months before changes in culture/serology. Patients who remained Pa-positive had significantly increased sIgA levels than patients who remained Pa-negative, both at the baseline (39.6 U/mL vs. 19.2 U/mL; p = 0.02) and at the end of the follow-up (119.4 U/mL vs. 25.2 U/mL; p < 0.001). No association was found between sIgA levels in saliva and emergence or recurrence of Pa in the LAW. A positive median sIgA result in the first year of follow-up implied up to 12.5-fold increased risk of subsequent Pa exposure in the LAW. Our test detected early changes in the P. aeruginosa LAW status and risk of exposure to P. aeruginosa in the LAW with two years in advance. Comparison with sinus culture is needed to assess the test's ability to identify CF patients in need of a sinus approach for Pa investigation, which could provide opportunities of Pa eradication before its aspiration to the lungs.

Nonlinear Attitude Control of a Spherical Underwater Vehicle.

In this work, we present the design, implementation, and testing of an attitude control system based on State Feedback Linearization (FL) of a prototype spherical underwater vehicle. The vehicle is characterized by a manifold design thruster configuration for both locomotion and maneuvering, as well as on a novel pendulum-based passive pitch control mechanism. First, the mechanical design and onboard electronics set up of the spherically shaped hull are introduced. Afterward, a high-fidelity dynamic model of the system is derived for a 6 degree-of-freedom (DOF) underwater vehicle, followed by several experiments that have been performed in a controlled environment to compare the performance of the proposed control method to that of a baseline Proportional-Integral-Derivative (PID) controller. Experimental results demonstrate that while both controllers were able to perform the specified maneuvers, the FL controller outperforms the PID in terms of precision and time response.

Distribution of Gadolinium in Rat Heart Studied by Fast Field Cycling Relaxometry and Imaging SIMS.

Research on microcirculatory alterations in human heart disease is essential to understand the genesis of myocardial contractile dysfunction and its evolution towards heart failure. The use of contrast agents in magnetic resonance imaging is an important tool in medical diagnostics related to this dysfunction. Contrast agents significantly improve the imaging by enhancing the nuclear magnetic relaxation rates of water protons in the tissues where they are distributed. Gadolinium complexes are widely employed in clinical practice due to their high magnetic moment and relatively long electronic relaxation time. In this study, the behavior of gadolinium ion as a contrast agent was investigated by two complementary methods, relaxometry and secondary ion mass spectrometry. The study examined the distribution of blood flow within the microvascular network in ex vivo Langendorff isolated rat heart models, perfused with Omniscan® contrast agent. The combined use of secondary ion mass spectrometry and relaxometry allowed for both a qualitative mapping of agent distribution as well as the quantification of gadolinium ion concentration and persistence. This combination of a chemical mapping and temporal analysis of the molar concentration of gadolinium ion in heart tissue allows for new insights on the biomolecular mechanisms underlying the microcirculatory alterations in heart disease.

Metal-Ligand Recognition Index Determination by NMR Proton Relaxation Study.

In this study, we developed and validated a new proposed parameter quantifying the interaction strength between natural and/or synthetic molecules with paramagnetic metal ions. The Metal ion Recognition Index, Miri, is a quantitative parameter to describe the proton environment and to define their involvement in the inner and/or outer sphere of the paramagnetic metal ion. The method is based on the analysis of NMR proton spin-lattice relaxation rates of a specific ligand in both the diamagnetic and paramagnetic conditions. The proposed procedure is also useful to calculate the ligand proton spin-lattice relaxation rate in the paramagnetic bound conditions, which is typically very difficult to determine experimentally. Miri was used to compare the ligand proton involvement toward different paramagnetic species, in particular the Copper(II)-Piroxicam system. Copper(II)-Piroxicam complex is one of the most active anti-inflammatory and anti-arthritic species. Miri provides an opportunity to improve our knowledge of metal-ligand complexes that play a fundamental role in bioinorganic interactions.

Ionic Exchange Resins and Hydrogels for Capturing Metal Ions in Selected Sweet Dessert Wines.

Samples of sweet and dessert wines, Vin Santo (VSR) from Malvasia grapes, and Granello (GR) from Sauvignon grapes were collected and analyzed for the content of selected macro- and micro-nutrients (Na, K, Mg, Ca, Mn, Fe, Cu and Zn) and of Pb. GR wines had low levels for Fe, Cu and Zn, when compared to VSR and in particular Zn was two orders of magnitude lower. Methods to decrease the content of Zn and Cu in VSR, as well as those for reducing, at the same time, the concentrations of Ca, Mg and K in both VSR and GR, to avoid the formation of opalescence and depots of metal tartrates, were studied. Synthetic hydrogels containing l-histidine residue were tested. The overall relative lowering effects were by ca 4, 23, and 12% for K, Mg and Ca contents, and ca 6, 27 and 10%, for Mn, Cu and Zn contents, in GR wine samples. Commercial ion exchange resin Lanxess Lewatit L-207 and L-208 were then assayed, being legally allowed in the agro-food industry. The L-207 resin revealed great lowering effects on the concentrations of Mn, Cu and Zn, being 75, 91 and 97%, respectively, in VSR wines and 77, 76 and 92%, respectively, in GR wines. The content of Zn was reduced from 49.3 ± 1.2 mg/L in the original wine, down to 1.1 ± 0.1 mg/L, within 48 h soaking. The effects on the character of the dessert wines by the resin L-207 was also taken under control, measuring pH and color index. The color index changed by ca 15% and pH by ca 6% upon treatment of VSR wine with L-207 resins (48 h).

Formulation of liposomes functionalized with Lotus lectin and effective in targeting highly proliferative cells.

BACKGROUND: Liposomes, used to improve the therapeutic index of new and established drugs, have advanced with the insertion of active targeting. The lectin from Lotus tetragonolobus (LTL), which binds glycans containing alpha-1,2-linked fucose, reveals surface regionalized glycoepitopes in highly proliferative cells not detectable in normally growing cells. In contrast, other lectins localize the corresponding glycoepitopes all over the cell surface. LTL also proved able to penetrate the cells by an unconventional uptake mechanism. METHODS: We used confocal laser microscopy to detect and localize LTL-positive glycoepitopes and lectin uptake in two cancer cell lines. We then constructed doxorubicin-loaded liposomes functionalized with LTL. Intracellular delivery of the drug was determined in vitro and in vivo by confocal and electron microscopy. RESULTS: We confirmed the specific localization of Lotus binding sites and the lectin uptake mechanism in the two cell lines and determined that LTL-functionalized liposomes loaded with doxorubicin greatly increased intracellular delivery of the drug, compared to unmodified doxorubicin-loaded liposomes. The LTL-Dox-L mechanism of entry and drug delivery was different to that of Dox-L and other liposomal preparations. LTL-Dox-L entered the cells one by one in tiny tubules that never fused with lysosomes. LTL-Dox-L injected in mice with melanoma specifically delivered loaded Dox to the cytoplasm of tumor cells. CONCLUSIONS: Liposome functionalization with LTL promises to broaden the therapeutic potential of liposomal doxorubicin treatment, decreasing non-specific toxicity. GENERAL SIGNIFICANCE: Doxorubicin-LTL functionalized liposomes promise to be useful in the development of new cancer chemotherapy protocols.

Design and Kinematic Modeling of a Soft Continuum Telescopic Arm for the Self-Assembly Mechanism of a Modular Robot.

In recent years, the development of mining robots has grown significantly, offering improved efficiency and safety in hazardous environments. However, there is still room for improvement in adaptability, scalability, and overall performance. The ROBOMINERS project, funded by the European Union's Horizon 2020 Research and Innovation Program, aims to facilitate Europe's access to mineral resources applying disruptive robotic concepts. One such concept is resilience, which can be achieved providing modular mining robots with the ability to reconfigure during operation. To address this challenge, this article presents the development and kinematic modeling of a soft, telescopic, continuum arm integrated into a modular robot. The arm serves as a mechanical interface for coupling different robotic modules or tools following the principle of the car crane. With a fully 3D-printed design, the arm features two sections of variable length that are driven by an innovative actuation method based on soft racks. It provides a 6 degrees of freedom (DoF) motion. The arm kinematic models are obtained by backbone parameterization assuming constant curvature and independent bending between sections for forward kinematics and applying a machine learning-based approach for inverse kinematics. The models are validated through the evaluation of two trajectories, measuring the deviation in each DoF and rack extension. Furthermore, a demonstration of the arm's coupling procedure between two robotic modules and one possible configuration of the robotic system showcases its functionality.

Bioinspired Whisker Sensor for 3D Mapping of Underground Mining Environments.

Traversing through challenging, unstructured environments, particularly in mining scenarios characterized by dust concentration, darkness, and lack of communication presents formidable obstacles for traditional sensing technologies. Drawing inspiration from naked mole rats, characterized as being skilled subterranean navigators that depend heavily on touch to navigate their environment, this study introduces a new whisker-sensing disk designed for 3D mapping in unstructured environments. The disk comprises a circular array of 32 whisker sensors, each featuring a slender flexible plastic rod attached to a compliant base housing a 3D Hall-effect sensor. The whisker sensor is modeled using both analytical and data-driven approaches to predict rotation angles based on magnetic field measurements. The validation and comparison of both models are performed by evaluating data from other whisker sensors. Additionally, a series of experiments demonstrates the whisker disk's capability in performing 3D-mapping tasks, along with successful implementation on diverse robotic platforms, highlighting its future potential for effective 3D mapping in complex and unstructured subterranean environments.

NOX2 and NOX4 expression in monocytes and macrophages-extracellular vesicles in signalling and therapeutics.

Extracellular vesicles (EVs) are a type of cytoplasmic vesicles secreted by a variety of cells. EVs originating from cells have been known to participate in cell communication, antigen presentation, immune cell activation, tolerance induction, etc. These EVs can also carry the active form of Nicotinamide Adenine Dinucleotide Phosphate Oxidase Hydrogen (NADPH) oxidase, which is very essential for the production of reactive oxygen species (ROS) and that can then modulate processes such as cell regeneration. The aim of this study is to characterize the EVs isolated from U-937 and THP-1 cells, identify the NADPH oxidase (NOX) isoforms, and to determine whether EVs can modulate NOX4 and NOX2 in monocytes and macrophages. In our study, isolated EVs of U-937 were characterized using dynamic light scattering (DLS) spectroscopy and immunoblotting. The results showed that the exogenous addition of differentiation agents (either phorbol 12-myristate 13-acetate (PMA) or ascorbic acid) or the supplementation of EVs used in the study did not cause any stress leading to alterations in cell proliferation and viability. In cells co-cultured with EVs for 72 h, strong suppression of NOX4 and NOX2 is evident when monocytes transform into macrophagic cells. We also observed lower levels of oxidative stress measured using immunoblotting and electron paramagnetic resonance spectroscopy under the EVs co-cultured condition, which also indicates that EVs might contribute significantly by acting as an antioxidant source, which agrees with previous studies that hypothesized the role of EVs in therapeutics. Therefore, our results provide evidence for NOX regulation by EVs in addition to its role as an antioxidant cargo.

Physiochemical Characterization of Lipidic Nanoformulations Encapsulating the Antifungal Drug Natamycin.

Natamycin is a tetraene polyene that exploits its antifungal properties by irreversibly binding components of fungal cell walls, blocking the growth of infections. However, topical ocular treatments with natamycin require frequent application due to the low ability of this molecule to permeate the ocular membrane. This limitation has limited the use of natamycin as an antimycotic drug, despite it being one of the most powerful known antimycotic agents. In this work, different lipidic nanoformulations consisting of transethosomes or lipid nanoparticles containing natamycin are proposed as carriers for optical topical administration. Size, stability and zeta potential were characterized via dynamic light scattering, the supramolecular structure was investigated via small- and wide-angle X-ray scattering and 1H-NMR, and the encapsulation efficiencies of the four proposed formulations were determined via HPLC-DAD.

Skin mycoflora of Cebus primates kept in captivity and semicaptivity.

BACKGROUND: This study was performed to determine the fungal mycoflora in healthy tufted capuchins primates (Cebus sp) kept in captivity and semicaptivity to allow a more realistic interpretation on the basis of fungi isolated from their skin. Furthermore, we aimed at evaluating the potential risk of infection to humans by fungi perpetuated in the tegument of monkeys of this genus. METHODS: For the collection of skin material, the carpet method was used, followed by seeding in Sabouraud dextrose agar culture media, Mycosel agar, Dermatophyte Test Medium and Sabouraud agar supplemented with olive oil. RESULTS: Seventeen genera of fungi were detected, being three of them isolated only in the captivity animals (Acremonium - Cephalosporium, Phoma and Trichosporon). The genera of fungi with the higher frequencies were identified in the semicaptivity capuchins (Fusarium, Aspergillus and Penicillium). CONCLUSIONS: Many of the genera of fungi identified are potential pathogens for immune-compromised monkeys and humans.