131,356 research outputs found
Seismic noise data and processing software used to test a low-cost 3C seismometer
No full textThis dataset contains data and matlab routines used to generate the figures included in the manuscript titled "Lab and Field Tests of a Low-Cost 3-Component Seismometer for Shallow Passive Seismic Applications", submitted by D. Arosio, A. Aguzzoli, L. Zanzi, L. Panzeri, and D. Scaccabarozzi to Journal of Geophysical Research - Solid Earth for peer review (February 2023)
A fistful of chemico-physical parameters crucial for 1H-NMR relaxation : the effect of size, shape and coating in iron oxides core-shell nanoparticles
No full textAn increasing awareness about novel medical applications of smaller, inorganic-based nanoparticles, possessing unique properties at the nanoscale, has led to a burst of research activities in the development of “nanoprobes” for diagnostic medicine and agents for novel, externally activated, therapies. In this research field, magnetic nanoparticles (MNPs) are prominent due to fundamental peculiar properties which make them particularly appealing to materials and biomedical applications.
In particular, much attention was devoted to MNPs useful as agents for Magnetic Resonance Imaging (MRI), Optical Imaging (OI) and Magnetic Fluid Hyperthermia (MFH), carriers for drugs and vectors for molecular targeting. The possibility to collect images of the regions where the MNPs are delivered through MRI and eventually OI (if functionalized with a luminescent molecule), is joint to their use under radio-frequency fields, with frequency of the order of 100 KHz, which causes a local release of heat directed to tumour cells (the MFH effect), possibly inducing their death. By such materials, theranostic agents can be obtained. On the other hand, in the field of drug delivery and molecular targeting, few examples of reproducible experiments using superparamagnetic nanoparticles are actually present in literature. Thus, the applications of MNPs to nanomedicine is currently of growing interest in the world.
The main objectives of my research group in the last decade was to contribute to the knowledge of physical mechanisms at the basis of MNPs used in biomedicine (especially MRI) and to propose some novel systems in strict collaboration with different research groups of chemists and biologists. I will present a mini-review of different case studies [1-4] where I show how the chemico-physical characteristics of MNPs are strictly correlated to their properties and can be partially interpreted with the most famous heuristic model [5] used in literature for NMR relaxivity profiles.
Key Words: magnetic nanoparticles, NMR relaxivity, nanomagnetism
References
1. F. Brero, M. Basini, M. Avolio, F. Orsini F., P. Arosio, C. Sangregorio, C. Innocenti, A. Guerrini, J Boucard, E. Ishow, M. Lecouvey, J. Fresnais, L. Lartigue, A. Lascialfari, Nanomaterials, 10 (2020) 1660-1672.
2. M. Basini, A. Guerrini, M. Cobianchi, F. Orsini, D. Bettega, M. Avolio, C. Innocenti, C. Sangregorio, A. Lascialfari, P. Arosio, Journal of Alloys and Compounds, 770 (2019), 58-66.
3. M. Basini, T. Orlando., P. Arosio, M.F. Casula, D. Espa, S. Murgia, C. Sangregorio, C. Innocenti, A. Lascialfari, J. Chem. Phys., 146 (2017), 034703.
4. Bordonali L., Kalaivani T., Sabareesh K.P.V., Innocenti C., Fantechi E., Sangregorio C., Casula M.F., Lartigue L., Larionova J., Guari Y., Corti M., Arosio P., Lascialfari A., Journal of Physics: Condensed Matter, 25 (2013), 066008
5. A. Roch, R.N. Muller, P. Gillis, J. Chem. Phys. 110 (1999) 5403-5411
Direct P-Wave Seismic Noise Interferometry for Groundwater Monitoring: A Modelling Study
No full textIn this study, we monitor the depth variation of an unconfined aquifer by applying seismic noise interferometry to synthetic data modelled with a 2D finite-difference software. We consider two models with the same subsurface geological structure, but with different water table levels representing two monitoring periods. The receivers are placed at the topographic surface and collect the seismic signals generated by a source located at the bottom of the aquifer to simulate a pumping system. First, cross-correlation of seismic traces with a reference one is used to produce interferograms (i.e., virtual surveys) for both the tested models. Then, direct P-wave arrivals identified in the two interferograms are compared through the stretching technique in order to estimate the relative velocity changes (dv/v). Finally, the estimated dv/v values are related to theoretical ones obtained using a reference subsurface model to produce the water level depth in the considered monitoring period.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Applied Geophysics and Petrophysic
Synthesis of dual action Smac/Zinc-Chelator conjugates as putative proapoptotic agents
No full textApoptosis, or programmed cell death, is a critical cell process in normal development and homeostasis of multicellular organisms. It is now recognized that dysfunction of the apoptosis machinery is a hallmark of cancer. Accordingly, targeting critical apoptosis regulators is an attractive approach for the development of new classes of therapies for the treatment of cancer and other human diseases.
The X-linked inhibitor of apoptosis protein (XIAP) is a member of IAP proteins that potently inhibit apoptosis[1]. XIAP contains three baculovirus IAP repeat (BIR) domains. The mechanism of action of XIAP entails its binding with initiator and effector caspases through its BIR domains. In cells, the anti-apoptotic function of XIAP is antagonized by Smac/DIABLO (second mitochondria-derived activator of caspases or direct IAP binding protein with low pI). Despite the rather complex structure of Smac, its short N-terminal AVPI sequence is sufficient to trigger the inactivation of anti-apoptotic XIAP[2]. Our research group has shown how small monomeric, AVPI-inspired Smac mimics can bind XIAP on its BIR3 domain with sub-micromolar potency[3,4]. Executioner caspase-3, -6 and -7 exist within the cytosol as inactive zymogens (procaspases) activated by limited proteolysis within their inter-domain linker, carried out by an initiator caspaseThe essential executioner caspase-3 is proteolytically activated by either caspase-8 or -9. Zinc ions co-localize with procaspase-3/caspase-3 and inhibit its enzymatic activity in the cell by direct interaction with an Asp-Asp-Asp (DDD) “safety catch” region[5]. Thus, in this work we coupled a zinc chelator moiety based on di(picolylamide)amine (DPA) and its N,N-bis(pyridin-2-ylmethyl)ethane-1,2-diamine (BPEN) derivative to pro-apoptotic Smac mimetics, synthesized starting from known intermediates 1 and 2.
Dual action Smac mimetic-zinc chelators 3 and 4 were prepared from compounds 1 and 2 as shown in Scheme 1 and characterized in vitro, using cell-free and cellular assays[6,7]. Their ability to bind XIAP BIR3 domain, to process pro-caspase-3 to caspase-3 and their cytotoxicity have been experimentally determined, and favorably compared with those of a potent Smac mimic compound, especially for the most potent, tribasic dual action compound 4. Furthermore, the Zinc affinity for both compounds was confirmed by fluorescence measurements.
References
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2. J. Chai, C. Du, J. W. Wu, S. Kyin, X. Wang, Y.Shi. Nature 2000, 406, 855-862
3. P. Seneci, A. Bianchi, C. Battaglia, L. Belvisi, M. Bolognesi, A. Caprini, F. Cossu, E. de Franco, M. de, D.
Delia, C. Drago, A. Khaled, D. Lecis, L. Manzoni, M. Marizzoni, E. Mastrangelo, M. Milani,I. Motto, E.
Moroni, D. Potenza, V. Rizzo, F. Servida, E. Turlizzi, M. Varrone, F. Vasile, C. Scolastico. Bioorg. Med.
Chem. 2009, 17, 5834–5856.
4. L. Manzoni, D. Arosio, L. Belvisi, A. Bracci, M. Colombo, D. Invernizzi, C. Scolastico. J. Org. Chem. 2005, 70,
4124-4132.
5. K. S. Putt, G. W. Chen, J. M. Pearson, J. S Sandhorst, M. S. Hoagland, J. Kwon, S. Hwang, H. Jin, M. I.
Churchwell, M. Cho, D. R. Doerge, W. G. Helferich, P. J. Hergenrother. Nat. Chem. Biol. 2006, 2, 543, 550
6. Z. Nikolovska-Coleska, R. Wang, X. Fang, H. Pan, Y. Tomita, P. Li, P.P. Roller, K. Krajewski, N.G. Saito, J.A.
Stuckey, S. Wang, Anal. Biochem. 2004, 332, 261-273.
7. Z. Nikolovska-Coleska, J.L. Meagher, S. Jiang, S.A. Kawamoto, W. Gao, H. Yi, D. Qin, P.P. Roller, J.A.
Stuckey, S. Wang, Anal. Biochem. 2008, 374, 87-98
La figura del sapere teologico secondo Bonaventura negli scritti di Marco Arosio († 2009)
No full textC’è un ambito di ricerca negli studi bonaventuriani – che non vi si limita – nel quale il nome di Marco Arosio e la relativa opera, che sta via via vedendo la luce grazie alle fatiche
di alcuni amici, è divenuto riferimento da cui è difficile prescindere. L’ambito di ricerca cui mi riferisco è la questione relativa allo statuto epistemologico della teologia, che rappresenta il nucleo centrale della ricerca del professore Arosio.
Nelle pagine che seguono si cercherà di mettere in luce il senso del suo percorso di ricerca come via preliminare per un’ulteriore analisi critica dei risultati dell’indagine scientifica storico-filosofica di Arosi
DER Participation in Ancillary Services Market: An Analysis of Current Trends and Future Opportunities
Get PDFIn an effort to push for low-carbon transition, national governments and regulatory authorities are working to define market structures and legislative frameworks able to effectively support the spreading of electricity production from renewables. To this purpose, the opening of national Ancillary Services Markets (ASMs) to Distributed Energy Resources (DERs) plays a key role. However, pricing schemes and rules in place (e.g., incentives) can act as a barrier to the supply of regulation services by small-sized and renewable-based power plants. In this context, the present work evaluates the economic opportunities for DERs provided by the provision of tertiary reserve and balancing control in the Italian ASM. The research is carried out through the collection and processing of price data from the Italian electricity and gas markets over 4 years (2019–2022). Considering a reference architecture where DER units bid on the market through a Balancing Service Provider, the potential revenues on the ASM of a non-programmable or partially programmable DER unit are compared to the earnings expected of a conventional power plant in order to highlight whether unfair competition can represent a barrier. Then, possible evolutions in the current remuneration schemes are analyzed, to evaluate whether they can be able to support a better DER integration. From the analysis, it emerges that, even if negative prices could be useful to increase the competitiveness of RES-based power plants for downward regulation, the loss of the incentives can act as a deterrent to the offering of services on the market by DERs. Therefore, other regulatory options, such as the incentives retention in case of downward regulation, could also be needed
An integrated computational and NMR study of the first peptidimimetic inhibitors of cadherin homophilic interaction
Get PDFCadherins are a large family of calcium-dependent cell adhesion molecules that are mostly expressed at intercellular junctions. They mediate cell-cell adhesion by forming homophilic dimers between the N-terminal extracellular domains of two cadherins on adjacent cells (Figure 1). Cadherins are known to play a key role in important physiological processes, such as tissue morphogenesis and stability, as well as in the immune system regulation [1]. Over the past 20 years, the expression and/or the dysregulation of several cadherins have been shown to correlate with tumor progression [2]. Thus, cadherins are becoming valuable diagnostic indicators as well as potential therapeutic targets. Figure 1. Cadherins as transmembrane cell adhesion receptors (taken from www.sigma-aldrich.com) Despite a growing interest in the field, the rational design of small ligands targeting cadherin protein-protein interactions is still in a very early stage. So far, only a N-cadherin antagonist cyclic peptide, ADH-1, has entered clinical trials in patients with advanced solid tumors, including epithelial ovarian cancer (EOC), where both N-(neuronal) and E (epithelial)-cadherin are expressed [3, 4].
Recently, our group set up a docking protocol to rationally design small peptidomimetic ligands mimicking the N- and E-cadherin adhesive homodimer interface. Accordingly, the first mimics based on the tetrapeptide sequence Asp1-Trp2-Val3-Ile4 (DWVI) of the N-terminal adhesion arm were achieved (by replacing the central dipeptide Trp2-Val3 with several scaffolds developed in our laboratories) and proved to inhibit adhesion of EOC cells with improved efficacy compared to the ADH-1 peptide, although still with millimolar potency [5]. The STD (Saturation Transfer Difference) bioaffinity NMR technique was applied in order to detect and study the binding epitopes of these compounds with the EC1-EC2 construct of the epithelial E-cadherin and to determine the K D value of the complexes. NMR data and Molecular Dynamics simulations suggest a highly dynamic behavior of both the ligand and the protein and prompt towards an integrated computational and experimental approach to design new small peptidomimetic molecules able to interfere efficiently with cadherin-mediated cell-cell adhesion. Acknowledgements: we gratefully acknowledge Ministero dell’Università e della Ricerca for financial support (FIRB project RBFR088ITV).
References
1) D. Leckband, S. Sivasankar, Curr. Opin. Cell Biol. 2012, 24, 620.
2) G. Berx, F. van Roy, Cold Spring Harbor Perspectives in Biology 2009, 1, a003129.
3) G. De Santis, S. Miotti, M. Mazzi, S. Canevari, A. Tomassetti, Oncogene 2009, 28, 1206.
4) N. Yarom, D. Stewart, R. Malik, J. Wells, L. Avruch, D. J. Jonker, Curr. Clin. Pharmacol. 2013, 8, 81.
5) F. Doro, C. Colombo, C. Alberti, D. Arosio, L. Belvisi, C. Casagrande, R. Fanel
Sex/Gender- and Age-Related Differences in β-Adrenergic Receptor Signaling in Cardiovascular Diseases
Get PDFSex differences in cardiovascular disease (CVD) are often recognized from experimental and clinical studies examining the prevalence, manifestations, and response to therapies. Compared to age-matched men, women tend to have reduced CV risk and a better prognosis in the premenopausal period. However, with menopause, this risk increases exponentially, surpassing that of men. Although several mechanisms have been provided, including sex hormones, an emerging role in these sex differences has been suggested for β-adrenergic receptor (β-AR) signaling. Importantly, β-ARs are the most important G protein-coupled receptors (GPCRs), expressed in almost all the cell types of the CV system, and involved in physiological and pathophysiological processes. Consistent with their role, for decades, βARs have been considered the first targets for rational drug design to fight CVDs. Of note, β-ARs are seemingly associated with different CV outcomes in females compared with males. In addition, even if there is a critical inverse correlation between β-AR responsiveness and aging, it has been reported that gender is crucially involved in this age-related effect. This review will discuss how β-ARs impact the CV risk and response to anti-CVD therapies, also concerning sex and age. Further, we will explore how estrogens impact β-AR signaling in women
Loewner equations on complete hyperbolic domains
No full textWe prove that, on a complete hyperbolic domain , any Loewner PDE associated with a Herglotz vector field of the form , where the eigenvalues of have strictly negative real part, admits a solution given by a family of univalent mappings which satisfies . If no real resonance occurs among the eigenvalues of , then the family is uniformly bounded in a neighborhood of the origin. We also give a generalization of Pommerenke's univalence criterion on complete hyperbolic domains
Multi criteria analysis supporting effective landslide modeling
No full textNumerical modeling may be an effective tool to predict the behavior of instable slopes provided that it relies on appropriate slope physical model. This is particular true for large-scale landslides, that generally feature intrinsic high spatial variability. For these large mass movements, it is crucial to assess the required spatial scale and input data accuracy for a correct numerical analysis of landslide. This paper investigates the role of the spatial scale and data accuracy in landslide modeling by considering as a testbed a Deep Seated Gravitational Slope Deformation (DSGSD) located in the North of Italy. Thanks to a large amount of available data, collected by means of geological and geophysical surveys, several numerical simulations with different resolutions (in term of geological and geomorphological settings) were performed. A comparison between the outcomes of the numerical models was accomplished through the use of a Multi Criteria Analysis (MCA) in order to evaluate landslide modeling with respect to numerical performance, investigations cost and time constraints. As a matter of fact, the high costs of detailed investigations often prevent an adequate slope assessment. Therefore, it is of primary importance to understand the role of input data on the effectiveness of numerical simulations. Hence, a decision support system capable to consider all these aspects is presented in order to define the best model as a trade-off between effectiveness, in terms of outcomes, and cost investigations
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