Search results for " DOC"
showing 10 items of 1281 documents
De novo design of protein kinase inhibitors by in silico identification of hinge region-binding fragments.
2013
Protein kinases constitute an attractive family of enzyme targets with high relevance to cell and disease biology. Small molecule inhibitors are powerful tools to dissect and elucidate the function of kinases in chemical biology research and to serve as potential starting points for drug discovery. However, the discovery and development of novel inhibitors remains challenging. Here, we describe a structure-based de novo design approach that generates novel, hinge-binding fragments that are synthetically feasible and can be elaborated to small molecule libraries. Starting from commercially available compounds, core fragments were extracted, filtered for pharmacophoric properties compatible w…
Involvment of docosanoïc acid (C22=0), and of very long chain fatty acids (tetracosanoïc acid (C24=0), hexacosanoïc acid (C26=0) in Alzheimer's disea…
2013
In the brain and in the plasma of patients with Alzheimer’s disease (AD), marked accumulation of C22:0 and of very long chain fatty acids (C24:0 ; C26:0) have been reported. Important decreases of docosahexaenoic acid (DHA; C22:6 n-3) have also been described as well as quantitative and qualitative modifications of plasmalogens. Altogether, these lipid modifications suggest an implication of peroxisomal metabolism disorders in the physiopathology of AD. Therefore, the biological activities of C22:0, C24:0 and C26:0 have been studied on human neuronal cells SK-N-BE. On these cells, the lipotoxicity of fatty acids (C22:0, C24:0 and C26:0) leads to various cellular modifications: topographical…
Benefits and Threats to Using Social Media for Presenting and Implementing Evidence.
2018
As a potential high-yield tool for disseminating information that can reach many people, social media is transforming how clinicians, the public, and policy makers are educated and find new knowledge associated with research-related information. Social media is available to all who access the internet, reducing selected barriers to acquiring original source documents such as journal articles or books and potentially improving implementation-the process of formulating a conclusion and moving on that decision. The use of social media for evidence dissemination/implementation of research has both benefits and threats. It is the aim of this Viewpoint to provide a balanced view of each. J Orthop…
Development of peptidomimetic boronates as proteasome inhibitors.
2013
Abstract Proteasome inhibition has emerged over the past decade as an effective therapeutic approach for the treatment of hematologic malignancies. It is a multicatalytic complex, whose proteolytic activity relies in three types of subunits: chymotrypsin-like (β5), trypsin-like (β2) and caspase-like (β1). Most important for the development of effective antitumor agents is the inhibition of the β5 subunits. In this context, the dipeptide boronate bortezomib (Velcade ® ) represents the first proteasome inhibitor approved by the FDA and the lead compound in drug discovery. This paper describes the synthesis and biological evaluation of a series of conformationally constrained pseudopeptide bor…
Una pequeña lámina de plomo con inscripción ibérica de paleografía arcaica del Pico de los Ajos (Yátova, València)
2021
espanolEn este trabajo editamos una pequena lamina de plomo hallada en el Pico de los Ajos (Yatova) en la campana de 2018. La lamina aparecio plegada y contiene una inscripcion iberica de una sola linea en cada cara que muy probablemente configure un solo texto completo. Sus caracteristicas formales son poco comunes, siendo el paralelo mas cercano el de las laminas votivas de El Amarejo. La presencia del elemento kutuŕ, frecuente en las inscripciones votivas rupestres, tambien apuntaria a una interpretacion religiosa. Desde el punto de vista paleografico, cabe senalar que se trata de un texto explicitamente dual, ya que conviven en el las dos variantes de te y ŕ. A pesar de que el contexto …
A Definitive Pharmacophore Modelling Study on CDK2 ATP Pocket Binders: Tracing the Path of New Virtual High-Throughput Screenings
2020
Cyclin Dependent Kinases-2 (CDK2) are members of serine/threonine protein kinases family. They play an important role in the regulation events of the eukaryotic cell division cycle, especially during the G1 to S phase transition. Experimental evidence indicate that excessive expression of CDK2s should cause abnormal cell cycle regulation. Therefore, since a long time, CDK2s have been considered potential therapeutic targets for cancer therapy. In this work, onehundred and forty-nine complexes of inhibitors bound in the CDK2-ATP pocket were submitted to short MD simulations (10ns) and free energy calculation. Comparison with experimental data (K<sub>i</sub>, K<sub>d</su…
Validation of Teacher Self-efficacy (QAI) Questionnaire
2021
Negli ultimi anni numerose ricerche nazionali e internazionali hanno messo in evidenza l’importanza della Teacher Self Efficacy. Nonostante nel panorama nazionale esistano già alcuni strumenti che indagano tale costrutto, si notano sovrapposizioni e divergenze nei diversi fattori presi in considerazione, quali ad esempio la percezione di autoefficacia relativa alla possibilità di agire sull’engagement degli studenti e sulla colla- borazione con la famiglia e altre figure professionali. Pertanto l’obiettivo del presente contributo consiste nella costruzione e validazione di un nuovo strumento che tenga conto di entrambi quest’ultimi aspetti. Lo strumento, costituito da 25 item, è stato so…
Studio del ruolo delle mutazioni “gatekeeper” V654A e T670I di c-kit kinase nell’interazione con inibitori attraverso un approccio misto Dinamica Mol…
2012
La sovraespressione del proto-oncogene c-kit è stata riscontrata nelle cellule ematopoietiche, nel cancro a piccole cellule del polmone e nei tumori stromali gastrointestinali1-3. L’importanza clinica dell’espressione di c-kit nei tumori ha indirizzato la ricerca verso inibitori di questa tirosina chinasi. Imatinib (Gleevec®) (in figura) è stato il primo farmaco utilizzato in terapia, ma la comparsa di mutazioni su c-kit ha portato ad una riduzione dell’efficacia o a completa resistenza a questo trattamento. In alternativa, altri composti si sono mostrati attivi anche nei confronti dei mutanti come ad esempio Sunitinib (Sutent®)4, ma la necessità di nuovi e più efficaci inibitori contro i m…
Spectroscopic, crystal structural, theoretical and biological studies of phenylacetohydrazide Schiff base derivatives and their copper complexes
2020
Two phenylacetohydrazide Schiff base derivatives: N’-(1-(2-hydroxyphenyl)ethylidene)-2-phenylacetohydrazide, HL1, and N’-((1-hydroxynaphthalen-2-yl)methylene)-2-phenylacetohydrazide, HL2, were synthesized. HL1 dimerizes in presence of HCl, probably via radical mechanism to give (2,2’-((1E)-hydrazine-1,2-diylidenebis(ethan-1-yl-1-ylidene))diphenol (DIM). Thermal reactions of Cu(II) ions with the two Schiff base ligands resulted in formation of the binuclear complexes [(CuL1)2] and [(CuL2)2]. The stoichiometry and structures of the reported compounds were investigated by several spectroscopic and analytical techniques. The structure of the HL1 ligand and its complex [(CuL1)2] as well as the D…
Camtasia Studio, creació d’animacions multimèdia educatives
2009
Camtasia Studio es un programa diseñado para la grabación en pantalla de ordenador y su posterior edición. De esta manera se pueden crear animaciones multimedia con capacidades interactivas de manera sencilla en comparación con los tradicionales editores de vídeo y/o animación. En este artículo se estudian la estructura de este programa y las posibilidades de su aplicación al entorno educativo.