179 research outputs found

    Tuning the polymorphism of the anti-VEGF G-rich V7t1 aptamer by covalent dimeric constructs

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    In the optimization process of nucleic acid aptamers, increased affinity and/or activity are generally searched by exploring structural analogues of the lead compound. In many cases, promising results have been obtained by dimerization of the starting aptamer. Here we studied a focused set of covalent dimers of the G-quadruplex (G4) forming anti-Vascular Endothelial Growth Factor (VEGF) V7t1 aptamer with the aim of identifying derivatives with improved properties. In the design of these covalent dimers, connecting linkers of different chemical nature, maintaining the same polarity along the strand or inverting it, have been introduced. These dimeric aptamers have been investigated using several biophysical techniques to disclose the conformational behavior, molecularity and thermal stability of the structures formed in different buffers. This in-depth biophysical characterization revealed the formation of stable G4 structures, however in some cases accompanied by alternative tridimensional arrangements. When tested for their VEGF165 binding and antiproliferative activity in comparison with V7t1, these covalent dimers showed slightly lower binding ability to the target protein but similar if not slightly higher antiproliferative activity on human breast adenocarcinoma MCF-7 cells. These results provide useful information for the design of improved dimeric aptamers based on further optimization of the linker joining the two consecutive V7t1 sequences

    Mini-uav remote control: a case study at Politecnico di Torino

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    Recent development of modern micro and nano technologies allows aerospace vehicles extremely small size to be constructed. Wide availability and mass production of small dimension components drastically reduce the price of such vehicles. This fact allows them to be constructed by Universities and it makes them useful for education. The Aerospace Systems Engineering Research Group (ASSET) at Politecnico di Torino the design, development and testing small, but quite complex, integrated systems. The goal of this paper is to present one of the contemporary works of this group: the Mini-UAV "ASSET" remote control/flight simulator site. This paper contains a short presentation of the Mini-UAV, a description of its onboard and ground systems and the use of COTS components. The paper explains how the ground control site has also been designed to run as a flight simulator. For this purpose MICROSOFT FLIGHT SIMULATOR for 3D scenario visualization and Matlab/Simulink for airplane and environmental modeling has been used and integrated. In the system are included possibilities of ALTIA Design software exploitation for avionic display visualization. In particular some new modes for HUD, conceived and simulated, are presented and discussed in the paper. The hardware configuration of the Remote Control System/Flight Simulator is briefly described

    Learning Interpretable Temporal Properties from Positive Examples Only

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    We consider the problem of explaining the temporal behavior of black-boxsystems using human-interpretable models. To this end, based on recent researchtrends, we rely on the fundamental yet interpretable models of deterministicfinite automata (DFAs) and linear temporal logic (LTL) formulas. In contrast tomost existing works for learning DFAs and LTL formulas, we rely on onlypositive examples. Our motivation is that negative examples are generallydifficult to observe, in particular, from black-box systems. To learnmeaningful models from positive examples only, we design algorithms that relyon conciseness and language minimality of models as regularizers. To this end,our algorithms adopt two approaches: a symbolic and a counterexample-guidedone. While the symbolic approach exploits an efficient encoding of languageminimality as a constraint satisfaction problem, the counterexample-guided onerelies on generating suitable negative examples to prune the search. Both theapproaches provide us with effective algorithms with theoretical guarantees onthe learned models. To assess the effectiveness of our algorithms, we evaluateall of them on synthetic data.<br

    Some properties of nilpotent groups

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    Property S, a finiteness property which can hold in infinite groups, was introduced by Stallings and others and shown to hold in free groups. In [2] it was shown to hold in nilpotent groups as a consequence of a technical result of Mal'cev. In that paper this technical result was dubbed property R. Hence, more generally, any property R group satisfies property S. In [7] it was shown that property R implies the following (labeled there weak property R) for a group G: If G₀ is any subgroup in G and G₀* is any homomorphic image of G₀, then the set of torsion elements in G₀* forms a locally finite subgroup. It was left as an open question in [7] whether weak property R is equivalent to property R. In this paper we give an explicit counterexample thereby proving that weak property R is strictly weaker than property R

    Survey of generalized pregroups and a question of Reinhold Baer

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    There has been recent interest in Stallings’ Pregroups. (See [2] and [12].) This paper gives a survey of generalized pregroups. We also answer a question of Reinhold Baer [1] on pregroups and answer a generalization of this question for generalized pregroups

    Energy neutral operation of vibration energy-harvesting sensor networks for bridge applications

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    greatly benefit from the use of wireless sensor networks (WSNs), however energy harvesting for the operation of the network remains a challenge in this setting. While solar and wind power are possible and credible solutions to energy generation, the need for positioning sensor nodes in shaded and sheltered locations, e.g., under a bridge deck, is also often precluding their adoption in real-world deployments. In some scenarios vibration energy harvesting has been shown as an effective solution, instead. This paper presents a multihop vibration energy-harvesting WSN system for bridge applications. The system relies on an ultra-low power wireless sensor node, driven by a novel vibration based energy-harvesting technology. We use a receiver-initiated routing protocol to enable energy-efficient and reliable connectivity between nodes with different energy charging capabilities. By combining real vibration data with an experimentally validated model of the vibration energy harvester, a hardware model, and the COOJA simulator, we develop a framework to conduct realistic and repeatable experiments to evaluate the system before on-site deployment. Simulation results show that the system is able to maintain energy neutral operation, preserving energy with careful management of sleep and communication times. We also validate the system through a laboratory experiment on real hardware against real vibration data collected from a bridge. Besides providing general guidelines and considerations for the development of vibration energy-harvesting systems for bridge applications, this work highlights the limitations of the energy budget made available by traffic-induced vibrations, which clearly shrink the applicability of vibration energy-harvesting technology for WSNs to applications that do not generate an overwhelming amounts of data

    3D GRID-based pharmacophore and Metadynamics approaches for the rational design of N-Methyl β-sheet breaker peptides as inhibitors of the Alzheimer's Aβ-amyloid fibrillogenesis

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    Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the loss of the cognitive functions and dementia. Several scientific evidences report that a central role in the pathogenesis of AD is played by the brain deposition of insoluble aggregates of β-amyloid protein (Aβ) proteins, thus causing neuronal cell death [1]. For this reason, one of the promising approach is to inhibit the aggregation of Aβ peptides. Because Aβ is self-assembling, one possible strategy to prevent this process is to use short peptide fragments homologous to the full-length wild-type Aβ protein. From this consideration, several short synthetic peptides were designed as beta-sheet breakers (BSB) [2]. In particular, the pentapetide Ac-LPFFD-NH2 (iAβ5p) exhibited a certain capability to inhibit Aβ fibrillogenesis [3]. iAβ5p analogs [4] were, then, designed by introducing N-Methylation at the amide bond nitrogen were also promising BSB. Here, we describe the methodological approach, which combines 3D GRID-based pharmacophore peptide screening with Well-Tempered Metadynamics simulations aimed to the discovery of novel N-Methylated BSB. This approach led us to identify two promising, cell permeable, N-Methylated peptides that were further evaluated for their BSB properties showing a significant improvement of the fibrillogenesis inhibition with respect to the lead iAβ5p

    Sea state monitoring by ship motion measurements onboard a research ship in the antarctic waters

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    A parametric wave spectrum resembling procedure is applied to detect the sea state parameters, namely the wave peak period and significant wave height, based on the measurement and analysis of the heave and pitch motions of a vessel in a seaway, recorded by a smartphone located onboard the ship. The measurement system makes it possible to determine the heave and pitch acceleration spectra of the reference ship in the encounter frequency domain and, subsequently, the absolute sea spectra once the ship motion transfer functions are provided. The measurements have been carried out onboard the research ship “Laura Bassi”, during the oceanographic campaign in the Antarctic Ocean carried out in January and February 2020. The resembled sea spectra are compared with the weather forecast data, provided by the global-WAM (GWAM) model, in order to validate the sea spectrum resembling procedure
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