1,721,258 research outputs found
Small molecule inhibitors of kdm5 histone demethylases increase the radiosensitivity of breast cancer cells overexpressing JARID1B
No full textNHERF1 (Na+/H+ exchanger 3 regulating factor 1) is an integral membrane adaptor protein carrying two NH2-terminal PDZ (postsynaptic density 95/discs large/zona occludens 1) tandem domains.1 PDZ1 (11-97 amino acids) and PDZ2 (150-237 amino acids) show 74% identity to each other and bind to specific carboxyl-terminal motifs on target proteins, such as -catenin and PTEN, that may have a pivotal role in tumorigenesis. Oncogenic activity of NHERF1 is strictly dictated by changes on its subcellular localization.1,2 A pharmacophore model was used to filter out an in-house training set of about 6000 compounds, leading to identify a potent inhibitor of NHERF1.3 We herein reported the design and synthesis of new NHERF1 inhibitors (Figure 1).4 The new compounds were synthesized by treating the appropriate indole with thionyl chloride and the proper amino derivative in the presence of pyridine in dichloromethane at room temperature for 12 h; alternatively, the coupling reaction was carried out using (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate and triethylamine in N,N-dimethylformamide at room temperature for 12 h. Compounds 5, 9, 10 and 13 exhibited a remarkable cytotoxicity in Ls174TshBeta-Cat cells. The binding to NHERF1 PDZ was confirmed by means of a dansylated peptide corresponding to the C-terminal sequence of Beta2-AR. When used in combination with antagonists of Beta-catenin, the new derivatives increased the apoptotic death of colorectal cancer cells refractory to currently available Wnt/Beta-catenin-targeted agents. References 1. Vaquero, J.; Nguyen Ho-Bouldoires, T. H.; Clapéron, A.; Fouassier, L. Oncogene 2017, 36, 3067‒3079. 2. Georgescu, M. M.; Morales, F. C.; Molina, J. R.; Hayashi, Y. Curr. Mol. Med. 2008, 8, 459−468. 3. Saponaro, C.; Sergio, S.; Coluccia, A.; De Luca, M.; La Regina, G.; Mologni, L.; Famiglini, V.; Naccarato, V.; Bonetti, D.; Gautier, C.; Gianni, S.; Vergara, D.; Salzet, M.; Fournier, I.; Bucci, C.; Silvestri, R.; Gambacorti Passerini, C.; Maffia, M.; Coluccia, A. M. L. Oncogene 2018, 37, 3301‒3316. 4. Coluccia, A.; La Regina, G.; Naccarato, V.; Nalli, M.; Orlando, V.; Biagioni, S.; De Angelis, M. L.; Baiocchi, M.; Gautier, C.; Gianni, S.; Di Pastena, F.; Di Magno, L.; Canettieri, G.; Coluccia, A. M. L.; Silvestri, R. ACS Med. Chem. Lett. 2019, 10, 499‒503
Multi-Channel and Multi-Agent Signal Processing
No full textMulti-channel and array signal processing is a well-established field with fundamental applications in wireless communications, radar/sonar, remote sensing, medical imaging, and more [...
Hybrid TOA/RSS range-based localization with self-calibration in asynchronous wireless networks
No full textOn the sum of random samples with bounded Pareto distribution
Full text linkHeavy-tailed random samples, as well as their sum or average, are encountered in a number of signal pro-cessing applications in radar, communications, finance, and natural sciences. Modeling such data through the Pareto distribution is particularly attractive due to its simple analytical form, but may lead to infinite variance and/or mean, which is not physically plausible: in fact, samples are always bounded in practice, namely because of clipping during the signal acquisition or deliberate censoring or trimming (truncation) at the processing stage. Based on this motivation, the paper derives and analyzes the distribution of the sum of right-censored Pareto Type-II variables, which generalizes the conventional Pareto (Type-I) and Lomax distributions. The distribution of the sum of truncated Pareto is also obtained, and an analytical connection is drawn with the unbounded case. A numerical analysis illustrates the findings, providing insights on several aspects, including the intimate mixture structure of the obtained expressions. An il-lustrative application to the analysis of real radar data is also provided. (c) 2021 Elsevier B.V. All rights reserved
AIDS e flussi informativi tra medico, paziente e autorità sanitaria, (in termini di partner notification e di contact tracing)
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Interaction-Based Distributed Learning in Cyber-Physical and Social Networks
Full text linkIn this paper, we consider a network scenario in which agents can evaluate each other according to a score graph that models some physical or social interaction. The goal is to design a distributed protocol, run by the agents, allowing them to learn their unknown state among a finite set of possible values. We propose a Bayesian framework in which scores and states are associated to probabilistic events with unknown parameters and hyperparameters, respectively. We prove that each agent can learn its state by combining a local Bayesian classifier with a (centralized) Maximum Likelihood (ML) estimator of the parameter-hyperparameter. To overcome the intractability of the ML problem, we provide two relaxed probabilistic models that lead to distributed estimation schemes with affordable complexity. In order to highlight the appropriateness of the proposed relaxations, we demonstrate the distributed estimators on a machine-to-machine testing setup for anomaly detection and on a social interaction setup for user profiling
Channel Gain Lower Bound for IRS-Assisted UAV-Aided Communications
No full textThe Multiple-Input-Multiple-Output (MIMO) capabilities of an Intelligent Reflective Surface (IRS) combined with the inherent versatility of an Unmanned Aerial Vehicle (UAV) can significantly enhance the communication quality between a Ground User (GU) and a Base Station (BS). This work proposes a composite channel gain expression for performance analysis in IRS-assisted UAV-aided networks under Rician fading conditions. Differently from the present literature, the proposed formulation takes into account wave interference among surface elements and with the receiver. Moreover, Orthogonal Frequency Multiple Access (OFDMA) is employed to cope with spatial-and frequency-selective fading, enabling direct application in multi-user multi-drone scenarios. Numerical results demonstrate that the proposed model provides an underestimate, as expected from theoretical analysis, from which a lower bound for the data rate can be obtained, to be practically employed for system design and assessment
The perception of physical health status in obsessive-compulsive disorder: A systematic review and meta-analysis
No full textBackground: Physical Health Status is a neglected outcome in clinical practice with Obsessive-Compulsive Disorder (OCD) and a systematic review is lacking. Objective: The current study presents the first systematic review and meta-analysis summarizing the evidence on (a) perceived Physical Health Status, Bodily Pain and Role Limitations due to Physical Problems in patients with OCD compared with controls, (b) age, gender, severity of OCD symptoms, study publication date, study methodological quality as moderators of perceived Physical Health Status. Methods: Case-control studies were included if they (a) compared OCD patients with healthy/general population participants as controls, and (b) used validated self-report instruments. Two reviewers searched electronic databases, contacted corresponding authors, and examined reference lists/conference proceedings/theses. Results: Fourteen studies were included. A large significant negative effect size without publication bias showed that controls reported higher perceived Physical Health Status than patients with OCD. Medium and small effect sizes favouring controls emerged for Role Limitations due to Physical Problems and Bodily Pain, respectively. Higher age, females percentage, and publication date were associated with larger effect sizes; higher OCD severity and methodological quality were associated with smaller effect sizes. Conclusion: Perceived Physical Health should be evaluated and addressed by clinicians during treatment, particularly with older, female and less severe patients. Lifestyle interventions might be implemented
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