Search results for "45"
showing 10 items of 1896 documents
Rational design of allosteric modulators of the aromatase enzyme: An unprecedented therapeutic strategy to fight breast cancer.
2019
Estrogens play a key role in cellular proliferation of estrogen-receptor-positive (ER+) breast cancers (BCs). Suppression of estrogen production by competitive inhibitors of the enzyme aromatase (AIs) is currently one of the most effective therapies against ER + BC. Yet, the development of acquired resistance, after prolonged treatments with AIs, represents a clinical major concern. Serendipitous findings indicate that aromatase may be non-competitively inhibited by clinically employed drugs and/or industrial chemicals. Here, by performing in silico screening on two putative allosteric sites, molecular dynamics and free energy simulations, supported by enzymatic and cell-based assays, we id…
Suitability ofMMGBSAfor the selection of correct ligand binding modes from docking results
2018
The estimation of the correct binding mode and affinity of a ligand into a target protein using computational methods is challenging. However, docking can introduce poses from which the correct binding mode could be identified using other methods. Here, we analyzed the reliability of binding energy estimation using the molecular mechanics-generalized Born surface area (MMGBSA) method without and with energy minimization to identify the likely ligand binding modes within docking results. MMGBSA workflow (a) outperformed docking in recognizing the correct binding modes of androgen receptor ligands and (b) improved the correlation coefficient of computational and experimental results of rescor…
On global solutions of the Maxwell-Dirac equations
1987
We prove, for the Maxwell-Dirac equations in 1+3 dimensions, that modified wave operators exist on a domain of small entire test functions of exponential type and that the Cauchy problem, inR+×R3, has a unique solution for each initial condition (att=0) which is in the image of the wave operator. The modification of the wave operator, which eliminates infrared divergences, is given by approximate solutions of the Hamilton-Jacobi equation, for a relativistic electron in an electromagnetic potential. The modified wave operator linearizes the Maxwell-Dirac equations to their linear part.
Negociación, guerra y "asientos". Financiar el elército de Flandes en el último tercio del reinado de Felipe II (1577-1596)
2019
El periodo comprendido entre 1575 y 1596 fue enormemente complejo a nivel político en los Países Bajos y no lo fue menos a nivel financiero para el ejército de Flandes. Estos años estuvieron enmarcados entre dos suspensiones de pagos en los que las negociaciones financieras fueron determinantes para la guerra en los Países Bajos, donde se dirimió la hegemonía hispánica en la Europa del siglo xVI. Estas negociaciones, que se dieron tanto a nivel global como a nivel local, fueron esenciales pagar conseguir aprovisionar al ejército de Flandes y mantener, por extensión, el dominio político y militar en los Países Bajos. Monarquía, ?asientos? y hombres de negocios crearon un cuerpo indivisible q…
Characterization of monoclonal antibodies generated against bovine and porcine prostacyclin synthase and quantitation of bovine prostacyclin synthase
1994
AbstractMonoclonal antibodies were raised against prostacyclin synthases purified from bovine and porcine aortae, respectively. Two monoclonal antibodies, RS1 and RS2, were purified and characterized. As shown by enzyme activity precipitation and Western blot analysis, in solubilized bovine and porcine aortae microsomes the monoclonal antibodies reacted only with prostacyclin synthase. The monoclonal antibody RS1 cross-reacts with partially purified prostacyclin synthase from human umbilical veins in an ELISA-based assay. None of the antibodies inhibited the enzyme activity. By combination of the monoclonal antibody RS2 with a polyclonal antibody we established an enzyme-linked immunosorben…
On Angels and Demons. Analysis of a sequence in the iconographic programme of the encyclopedic moralization of fin´amors in Matfré Ermengaud´s Brevia…
2017
En el present treball parem esment a 3 il·luminacions del Breviari d’Amor de Matfré Ermengaut que són ben eloqüents –valga la sinestèsia: imatges que són eloqüents— de la vocació d’Ermengaut en pro de la cristianització de la fin’amors. A més, estableixen una mena de seqüència en el concert de diàleg entre història natural, història sagrada i atenció a l’amor, als amadors, a fi i efecte que estableix qui és el receptor concret de l’obra, qui el model a seguir (els àngels) i qui a defugir (el dimoni), i quin és l’àmbit d’actuació del «maligne» : la societat cortés, ecosistema de la fin’amor. This paper analyzes three illuminations of Matfré Ermengaud´s Breviari d´Amor which represent the aut…
Ligand Diversity of Human and Chimpanzee CYP3A4: Activation of Human CYP3A4 by Lithocholic Acid Results from Positive SelectionS⃞
2009
For currently unknown reasons, the evolution of CYP3A4 underwent acceleration in the human lineage after the split from chimpanzee. We investigated the significance of this event by comparing Escherichia coli-expressed CYP3A4 from humans, chimpanzee, and their most recent common ancestor. The expression level of chimpanzee CYP3A4 was ∼50% of the human CYP3A4, whereas ancestral CYP3A4 did not express in E. coli. Steady-state kinetic analysis with 7-benzyloxyquinoline, 7-benzyloxy-4-(trifluoromethyl)coumarin (7-BFC), and testosterone showed no significant differences between human and chimpanzee CYP3A4. Upon addition of α-naphthoflavone (25 μM), human CYP3A4 showed a slightly decreased substr…
Les catastrophes naturelles au Moyen Âge (XIIe-XVe siècle)
2017
International audience; Catastrophe : le terme renvoie dans nos représentations contemporaines à des images de destruction, de désorganisation sociale et éventuellement de mort de masse. Les événements tels que les inondations, les tremblements de terre, les tempêtes, etc., sont inévitablement pensés sur le mode du drame et de la tragédie. Viennent à l'esprit la nécessité de comprendre l'événement à travers un bilan des pertes matérielles et surtout humaines, la détresse des populations sinistrées, le devoir gouvernemental et non-gouvernemental de développer l'aide humanitaire, et le nécessaire travail de mémoire d'un malheur collectif. C’est en considérant ce faisceau de réaction en tant q…
Hierarchical multi-criteria analysis for the selection of a triathlon
2018
Sports activities have an increasingly large impact in different fields: economy, tourism, environment, applied technology, social, culture, etc. This study analyses the most important criteria that triathletes take into account when choosing a triathlon event in Spain. The methodology used was Analytic Hierarchy Process (AHP), which quantifies the weighting of each criterion and sub-criterion in a survey. The survey was drawn up using 14 triathlete experts and was completed by 95 triathlon participants. The results show that the internal aspects associated with the development of the triathlon event, together with the proximity to the athlete's home, the layout and signage of the circuits …
On deterministic solutions for multi-marginal optimal transport with Coulomb cost
2022
In this paper we study the three-marginal optimal mass transportation problem for the Coulomb cost on the plane $\R^2$. The key question is the optimality of the so-called Seidl map, first disproved by Colombo and Stra. We generalize the partial positive result obtained by Colombo and Stra and give a necessary and sufficient condition for the radial Coulomb cost to coincide with a much simpler cost that corresponds to the situation where all three particles are aligned. Moreover, we produce an infinite class of regular counterexamples to the optimality of this family of maps.