105,855 research outputs found
“Sotto il sole di Omero”
No full textQui dico che La Facoltà di Bari si è costruita e tutt’oggi continua a crescere dall’intuizione, geniale, di Claudio D’Amato, sotto il sole di Omero, come diceva lui, attraverso un preciso modello di insegnamento ottenuto da chiare scelte e significativi riferimenti teorici.
Questa Scuola di Architettura parte dal principio, inequivocabile direi, che l’Architettura è l’Arte del Costruire, basata su uno stretto rapporto con la Storia, da leggere e rileggere con un analitico metodo critico, quello del “paesaggio mediterraneo” come luogo dell’abitare, dal valore concreto e pragmatico.
Questa Scuola, la Sua scuola, ha avuto un percorso articolato e complesso, non consequenziale, che durante tutti questi anni ha osservato come spettatore attivo, tracciandone sempre percorsi basati sulla stessa idea di Architettura. La costruzione in pietra, da una scelta possibile tra le tante, divenne una condizione necessaria per determinare ed interpretare con coerenza i significati, le forme e le identità di un luogo così peculiare come la Puglia
CHAPTER 17: Allosteric Inhibition of Abl Kinase
No full textEver since when the mechanism of allosteric regulation was postulated for the first time in 1965 by Monod, Wyman and Changeux, fifty years have passed. From that moment our vision and understanding of the ligand-protein interaction process have been completely changed. Proteins started to be considered not fixed biological entities but flexible structures endowed with an activity which could be finely tuned by interaction with other proteins or new small molecules able to bind pockets different from the catalytic sites.
In the following chapter an in depth description of one of the most studied allosteric modulation mechanism will be provided. c-Abl protein kinase represents a noteworthy example of how a small post-traductional modification (myristoylation of the N-terminal region in the protein sequence) can drive a complex mechanism of domains’ rearrangements, determining the activation state of the enzyme. Many efforts have been devoted from scientists all around the world in studying the molecular basis for the autoinhibition mechanism of c-Abl, and its derived oncogenic protein Bcr-Abl, leading to the identification of the first allosteric inhibitor GNF-5 actually involved in a Phase I clinical trial for the treatment of Chronic Myelogenous Leukemia (CML)
Time series clustering of online gambling activities for addicted users’ detection
No full textPeres, F., Fallacara, E., Manzoni, L., Castelli, M., Popovič, A., Rodrigues, M., & Estevens, P. (2021). Time series clustering of online gambling activities for addicted users’ detection. Applied Sciences (Switzerland), 11(5), [2397]. https://doi.org/10.3390/app11052397Ever since the worldwide demand for gambling services started to spread, its expansion has continued steadily. To wit, online gambling is a major industry in every European country, generating billions of Euros in revenue for commercial actors and governments alike. Despite such evidently beneficial effects, online gambling is ultimately a vast social experiment with potentially disastrous social and personal consequences that could result in an overall deterioration of social and familial relationships. Despite the relevance of this problem in society, there is a lack of tools for characterizing the behavior of online gamblers based on the data that are collected daily by betting platforms. This paper uses a time series clustering algorithm that can help decision-makers in identifying behaviors associated with potential pathological gamblers. In particular, experimental results obtained by analyzing sports event bets and black jack data demonstrate the suitability of the proposed method in detecting critical (i.e., pathological) players. This algorithm is the first component of a system developed in collaboration with the Portuguese authority for the control of betting activities.publishersversionpublishe
Optimization of aminoimidazole derivatives as Src family kinase inhibitors
No full textProtein kinases have emerged as crucial targets for cancer therapy over the last decades. Since 2001, 40 and 39 kinase inhibitors have been approved by FDA and EMA, respectively, and the majority are antineoplastic drugs. Morevoer, many candidates are currently in clinical trials. We previously reported a small library of 4-aminoimidazole and 2-aminothiazole derivatives active as Src family kinase (SFK) inhibitors. Starting from these results, we decided to perform an optimization study applying a mix and match strategy to identify a more potent generation of 4-aminoimidazoles. Firstly, a computational study has been performed, then compounds showing the best predicted docking scores were synthesized and screened in a cell-free assay for their SFK inhibitory activity. All the new chemical entities showed IC(50)s in the nanomolar range, with 2-130 fold increased activities compared to the previously reported inhibitors. Finally, the most active compounds have been tested on three cancer cell lines characterized by Src hyperactivation. Compounds 4k and 4l showed an interesting antiproliferative activity on SH-SY5Y neuroblastoma (NB) cell line. In this assay, the compounds resulted more potent than dasatinib, a tyrosine kinase inhibitor approved for the treatment of leukemias and in clinical trials for NB
The Vault of the Hôtel de Ville in Arles
No full textThe vault of the Arles City Hall, or Hôtel de Ville, represents the architect’s revenge on the corporations of masons. Completed in 1676, the relationship of span to rise of the vault make it the boldest work of masonry in Europe, and while this complex vault appears to be a unitary
structure, two vaults actually share the work, leaning against each other on the big arch. Bibliographic and archival research showed that surveys of the vault were missing; the only ancient survey was lost in the 1970s. A recent survey campaign made an analysis possible, eading to a hypothesis about the architect Mansart’s choices, based on hypothetical solutions to resolve the formal construction issues of the
vault. A connoisseur of geometry and optics, Mansart knew that the human eye was unable to perceive the exact geometry of a surface. Knowing that he couldn’t control the intersections of vault portions and then the joints of the rows in the space, he introduced a solution that involved drawing the intersections in plan and then projecting them on the vault to obtain the spatial intersections. No further constructions of the bold type followed the vaulted space in the Hôtel de ville, because the spatial research that linked the new discipline (stereotomy) to the quality of architectural space had by then come to an end
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
High-throughput docking for the identification of new influenza A virus polymerase inhibitors targeting the PA-PB1 protein-protein interaction
No full textA high-throughput molecular docking approach was successfully applied for the selection of potential inhibitors of the Influenza RNA-polymerase which act by targeting the PA-PB1 protein-protein interaction. Commercially available compounds were purchased and biologically evaluated in vitro using an ELISA-based assay. As a result, some compounds possessing a 3-cyano-4,6-diphenyl-pyridine nucleus emerged as effective inhibitors with the best ones showing IC50 values in the micromolar range
Appropriate Similarity Measures for Author Cocitation Analysis
No full textWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Square Dancing with the Stars to Enhance Dynamic Hirschman Linkages?
No full textIn this Presidential Address, the author takes the reader on a reconnaissance of his life and time as a regional scientist. He points out scenery he found scintillating along the way, hoping that some may pick up the banner and chew on a few of the ideas for a while. He suggests a revisit to Albert O. Hirschman’s notion of key sectors and more empirical analysis related to Marcus Berliant’s and Masahisa Fujita’s notion of knowledge creation and transfer.Presidential Address, San Antonio, Texas, March 29, 2014 (53rd Meetings of the Southern Regional Science Association
Pyrazolo[3,4-d]pyrimidines as tyrosine kinase inhibitors: synthesis and biological evaluation
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