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51.
Enrico Mario Alessandro Fassi Mariangela Garofalo Jacopo Sgrignani Michele Dei Cas Matteo Mori Gabriella Roda Andrea Cavalli Giovanni Grazioso 《International journal of molecular sciences》2022,23(9)
(1) Background: Disfunctions in autophagy machinery have been identified in various conditions, including neurodegenerative diseases, cancer, and inflammation. Among mammalian autophagy proteins, the Atg8 family member GABARAP has been shown to be greatly involved in the autophagy process of prostate cancer cells, supporting the idea that GABARAP inhibitors could be valuable tools to fight the progression of tumors. (2) Methods: In this paper, starting from the X-ray crystal structure of GABARAP in a complex with an AnkirinB-LIR domain, we identify two new peptides by applying in silico drug design techniques. The two ligands are synthesized, biophysically assayed, and biologically evaluated to ascertain their potential anticancer profile. (3) Results: Two cyclic peptides (WC8 and WC10) displayed promising biological activity, high conformational stability (due to the presence of disulfide bridges), and Kd values in the low micromolar range. The anticancer assays, performed on PC-3 cells, proved that both peptides exhibit antiproliferative effects comparable to those of peptide K1, a known GABARAP inhibitor. (4) Conclusions: WC8 and WC10 can be considered new GABARAP inhibitors to be employed as pharmacological tools or even templates for the rational design of new small molecules. 相似文献
52.
53.
Lucia Padalino Marcella Mastromatteo Lucia Lecce Sara Spinelli Francesco Contò Matteo Alessandro Del Nobile 《International Journal of Food Science & Technology》2014,49(6):1544-1556
The goal of the study was to obtain spaghetti enriched with pea flour with sensory properties close to conventional pasta. To this aim, the study has been organised in two subsequent trials. In the first, the pea flour amount added to the spaghetti was continuously increased until the overall sensory quality reached its threshold value (pea flour concentration = 15%). In fact, the spaghetti samples supplemented with 15% pea flour (15%S‐P) showed less elasticity, unpleasant colour and higher firmness compared to the control sample (CTRL). The second step was aimed to improve the overall sensory quality of the 15%S‐P spaghetti by means of guar gum (GUAR). The sample with GUAR (15%S‐P/GUAR) showed a pleasant colour, odour and taste. Furthermore, the 15%S‐P/GUAR sample recorded a low starch digestibility value (i.e. 54) and a higher soluble fibre content with respect to the 15%S‐P sample. 相似文献
54.
Leonardo Vanneschi Matteo Mondini Martino Bertoni Alberto Ronchi Mattia Stefano 《Genetic Programming and Evolvable Machines》2013,14(4):431-455
Genetic programming researchers have shown a growing interest in the study of gene regulatory networks in the last few years. Our team has also contributed to the field, by defining two systems for the automatic reverse engineering of gene regulatory networks called GRNGen and GeNet. In this paper, we revise this work by describing in detail the two approaches and empirically comparing them. The results we report, and in particular the fact that GeNet can be used on large networks while GRNGen cannot, encourage us to pursue the study of GeNet in the future. We conclude the paper by discussing the main research directions that we are planning to investigate to improve GeNet. 相似文献
55.
A Lyapunov method for stability analysis of piecewise-affine systems over non-invariant domains 总被引:1,自引:0,他引:1
Matteo Rubagotti Luca Zaccarian Alberto Bemporad 《International journal of control》2016,89(5):950-959
This paper analyses stability of discrete-time piecewise-affine systems, defined on possibly non-invariant domains, taking into account the possible presence of multiple dynamics in each of the polytopic regions of the system. An algorithm based on linear programming is proposed, in order to prove exponential stability of the origin and to find a positively invariant estimate of its region of attraction. The results are based on the definition of a piecewise-affine Lyapunov function, which is in general discontinuous on the boundaries of the regions. The proposed method is proven to lead to feasible solutions in a broader range of cases as compared to a previously proposed approach. Two numerical examples are shown, among which a case where the proposed method is applied to a closed-loop system, to which model predictive control was applied without a-priori guarantee of stability. 相似文献
56.
Intrinsic Fluorescence of the Active and the Inactive Functional Forms of Human Thymidylate Synthase
Dr. Simone Vitiello Dr. Monica Caselli Dr. Giorgia Pavesi Dr. Matteo Santucci Dr. Stefania Ferrari Prof. Maria Paola Costi Prof. Glauco Ponterini 《Chembiochem : a European journal of chemical biology》2021,22(10):1800-1810
The observables associated with protein intrinsic fluorescence – spectra, time decays, anisotropies – offer opportunities to monitor in real time and non-invasively a protein‘s functional form and its interchange with other forms with different functions. We employed these observables to sketch the fluorometric profiles of two functional forms of human thymidylate synthase (hTS), a homodimeric enzyme crucial for cell proliferation and thus targeted by anticancer drugs. The protein takes an active and an inactive form. Stabilization of the latter by peptides that, unlike classical hTS inhibitors, bind it at the monomer/monomer interface offers an alternative inhibition mechanism that promises to avoid the onset of drug resistance in anticancer therapy. The fluorescence features depicted herein can be used as tools to identify and quantify each of the two protein forms in solution, thus making it possible to investigate the kinetic and thermodynamic aspects of the active/inactive conformational interchange. Two examples of fluorometrically monitored interconversion kinetics are provided. 相似文献
57.
Lo?c Petigny Sandrine Périno Matteo Minuti Francesco Visinoni Jo?l Wajsman Farid Chemat 《International journal of molecular sciences》2014,15(5):7183-7198
Microwave extraction and separation has been used to increase the concentration of the extract compared to the conventional method with the same solid/liquid ratio, reducing extraction time and separate at the same time Volatile Organic Compounds (VOC) from non-Volatile Organic Compounds (NVOC) of boldo leaves. As preliminary study, a response surface method has been used to optimize the extraction of soluble material and the separation of VOC from the plant in laboratory scale. The results from the statistical analysis revealed that the optimized conditions were: microwave power 200 W, extraction time 56 min and solid liquid ratio of 7.5% of plants in water. Lab scale optimized microwave method is compared to conventional distillation, and requires a power/mass ratio of 0.4 W/g of water engaged. This power/mass ratio is kept in order to upscale from lab to pilot plant. 相似文献
58.
Milad Memarzadeh Matteo Pozzi 《Computer-Aided Civil and Infrastructure Engineering》2016,31(6):403-415
Operation and maintenance of an infrastructure system rely on information collected on its components, which can provide the decision maker with an accurate assessment of their condition states. However, resources to be invested in data gathering are usually limited and observations should be collected based on their Value of Information (VoI). Assessing the VoI is computationally intractable for most applications involving sequential decisions, such as long‐term infrastructure maintenance. In this article, we propose an approach for integrating adaptive maintenance planning based on Partially Observable Markov Decision Process (POMDP) and inspection scheduling based on a tractable approximation of VoI. Two alternative myopic approaches, namely pessimistic and optimistic, are introduced, and compared theoretically and by numerical examples. 相似文献
59.
Devis Bellucci Antonella Sola Matteo Gazzarri Federica Chiellini Valeria Cannillo 《Materials science & engineering. C, Materials for biological applications》2013,33(3):1091-1101
Since the 1970s, various types of ceramic, glass and glass–ceramic materials have been proposed and used to replace damaged bone in many clinical applications. Among them, hydroxyapatite (HA) has been successfully employed thanks to its excellent biocompatibility. On the other hand, the bioactivity of HA and its reactivity with bone can be improved through the addition of proper amounts of bioactive glasses, thus obtaining HA-based composites. Unfortunately, high temperature treatments (1200 °C ÷ 1300 °C) are usually required in order to sinter these systems, causing the bioactive glass to crystallize into a glass–ceramic and hence inhibiting the bioactivity of the resulting composite. In the present study novel HA-based composites are realized and discussed. The samples can be sintered at a relatively low temperature (800 °C), thanks to the employment of a new glass (BG_Ca) with a reduced tendency to crystallize compared to the widely used 45S5 Bioglass®. The rich glassy phase, which can be preserved during the thermal treatment, has excellent effects in terms of in vitro bioactivity; moreover, compared to composites based on 45S5 Bioglass® having the same HA/glass proportions, the samples based on BG_Ca displayed an earlier response in terms of cell proliferation. 相似文献
60.
Fabio LicciardelloPierangelo Frisullo Janine LaverseGiuseppe Muratore Matteo Alessandro Del Nobile 《Journal of food engineering》2012,108(3):453-462
Meringues are characterized by a predominant air phase and their overall quality is intimately related with microstructure. The formation of meringues microstructure relies on the capacity of egg white (EW) proteins to form voluminous and stable foams and it is ultimately related with the chemical properties of proteins and with the addition of ingredients such as sugars, salts, acids and surfactants.The study aimed at assessing the influence of sugar/EW ratio, citric acid and EW type on the microstructural and mechanical properties of meringues. Meringues prepared with different sugar/EW, citric acid level and different EW type were subjected to microstructural analysis by X-ray microtomography and to mechanical assessment by compression tests.Results demonstrate the ability of X-ray microtomography to reconstruct the 3D microstructure of meringues allowing the measurement of porosity, size, shape and distribution of pores. Citric acid, sugar concentration and EW type play a fundamental role on meringues microstructural parameters and mechanical properties. Low sugar/EW ratios as well as increasing citric acid levels increase the air phase and result in a softer texture of meringues. Moreover, low sugar/EW ratios and increasing citric acid in the meringue result in a reduction of pore size and also influence the shape of pores. Meringues microstructural and mechanical properties are affected by the EW quality: fresh and pasteurized EWs and EWs stored at refrigerated temperatures scored the highest structural and mechanical performances, while powdered and frozen EWs and albumens from old eggs showed the worst results. Not only the balance among ingredients but also the choice of raw materials can strongly affect the final quality of meringues. 相似文献