2,911 research outputs found
Combined therapies of antithrombotics and antioxidants delay in silico brain tumor progression
Glioblastoma multiforme, the most frequent type of primary brain tumor, is a
rapidly evolving and spatially heterogeneous high-grade astrocytoma that
presents areas of necrosis, hypercellularity and microvascular hyperplasia. The
aberrant vasculature leads to hypoxic areas and results in an increase of the
oxidative stress selecting for more invasive tumor cell phenotypes. In our
study we assay in silico different therapeutic approaches which combine
antithrombotics, antioxidants and standard radiotherapy. To do so, we have
developed a biocomputational model of glioblastoma multiforme that incorporates
the spatio-temporal interplay among two glioma cell phenotypes corresponding to
oxygenated and hypoxic cells, a necrotic core and the local vasculature whose
response evolves with tumor progression. Our numerical simulations predict that
suitable combinations of antithrombotics and antioxidants may diminish, in a
synergetic way, oxidative stress and the subsequent hypoxic response. This
novel therapeutical strategy, with potentially low or no toxicity, might reduce
tumor invasion and further sensitize glioblastoma multiforme to conventional
radiotherapy or other cytotoxic agents, hopefully increasing median patient
overall survival time.Comment: 8 figure
RanBP2-Mediated SUMOylation Promotes Human DNA Polymerase Lambda Nuclear Localization and DNA Repair
Cellular DNA is under constant attack by a wide variety of agents, both endogenous and exogenous. To counteract DNA damage, human cells have a large collection of DNA repair factors. Among them, DNA polymerase lambda (Polλ) stands out for its versatility, as it participates in different DNA repair and damage tolerance pathways in which gap-filling DNA synthesis is required. In this work we show that human Polλ is conjugated with Small Ubiquitin-like MOdifier (SUMO) proteins both in vitro and in vivo, with Lys27 being the main target of this covalent modification. Polλ SUMOylation takes place in the nuclear pore complex and is mediated by the E3 ligase RanBP2. This post-translational modification promotes Polλ entry into the nucleus, which is required for its recruitment to DNA lesions and stimulated by DNA damage induction. Our work represents an advance in the knowledge of molecular pathways that regulate cellular localization of human Polλ, which are essential to be able to perform its functions during repair of nuclear DNA, and that might constitute an important point for the modulation of its activity in human cells
DES-Type Interactions To Promote Solvent-Free and Metal-Free Reactions between Nitrogen-Containing Heterocycles and Allylic Alcohols
Nitrogen-containing heterocycles are of great interest to organic chemists since they are present in a wide array of bioactive molecules. The use of allylic alcohols to carry out the allylation of heterocycles has been described as a sustainable alternative for this type of functionalization. Among the plethora of methodologies described, the use of metals, solvents, or hazardous reagents is ubiquitous. The protocol described in this work has provided a solventless and metal-free alternative, being mediated by the easy-to-synthesise and reusable 1,3-bis(carboxymethyl)imidazolium chloride. The protocol has resulted compatible with several nitrogen-containing heterocycles (i.e. indole, pyrazole, triazole, tetrazole, carbazole, indazole, and benzotriazole) and allylic alcohols, providing the allylated-heterocycles with up to quantitative yield, being possible to perform the reaction in preparative scale.Based on various green metrics (atom economy, stoichiometric factor, reaction mass efficiency, materials recovery parameter, E-factor, and EcoScale), the overall greenness significance of the methodology has been established.This work was financially supported by the University of Alicante (VIGROB-316, UADIF20-106, UAUSTI21-15), the Spanish Ministerio de Ciencia, Innovación y Universidades (PGC2018-096616-B-I00), the Spanish Ministerio de Ciencia e Innovación (PID2021-127332NB-I00) and the Generalitat Valenciana (AICO/2021/013). MM thanks the ISO (University of Alicante) for a predoctoral contract
Georreferenciando la corrupción urbanística en España
Se plantea que, en el vertiginoso incremento de la actividad urbanística acaecida en España a lo largo de
la última década, el papel de la propiedad del suelo sigue teniendo un protagonismo clave en la vida
económica de nuestro país. Lo inmobiliario o, en un sentido más amplio, lo urbano -pues hay que añadir las
infraestructuras- se materializa sobre el soporte suelo. Pero este soporte, esta base se encuentra dividida,
fragmentada por la propiedad privada, la cual, a través de una serie de hechos administrativos
(planeamiento) persigue su reclasificación (de rústico a urbano), permitiendo a sus titulares la obtención de
rentas millonarias. Y es en este marco en el que se fragua la llamada “corrupción urbanística”, que muestra,
con claridad meridiana, la subordinación de la política a los intereses de ciertos grupos económicos
(propietarios de suelo, constructores y promotores inmobiliarios).
Planteado el problema, se emprendió un amplio estudio que, partiendo del análisis de las fuentes
periodísticas y estadísticas oficiales (censos de población y viviendas para los años 1991, 2001 y
estimaciones para 2008) y de su tratamiento en bases de datos y Sistemas de Información Geográfica (ArcGis
9.2), ha dado como resultado una variada cartografía a diferentes niveles (municipal, provincial y de
comunidades autónomas) del llamado “urbanismo irregular” en España en el período 2000-2010.The last decade witnessed an increase in the urban development activity in Spain. Land ownership has
played a crucial role within it. Real state processes take place (materialize) around the element of soil, but the
soil turns out to be fragmented by private property. And the latter, through administrative mechanisms,
pursues its relabeling from “rural” to “urban”. As a result, big owners of land obtain millionaire incomes. In this context, the so-called “urban development corruption” appears: the subordination of politics to the
interests of a number of economic groups (land owners, builders and real estate promoters).
A thorough study has been undertaken, which analyzed journalistic sources and official statistics. They were
later introduced into a database and a Geographic Information system (Arc gis 9.2). This has yielded a
cartography of “irregular urbanism” at different scales (municipal, provincial and autonomous communities)
in the period from 2000 to 2010
Characterizing the Aperiodicity of Irreducible Markov Chains by Using P Systems
It is well known that any irreducible and aperiodic Markov chain has exactly
one stationary distribution, and for any arbitrary initial distribution, the sequence of
distributions at time n converges to the stationary distribution, that is, the Markov
chain is approaching equilibrium as n ! 1.
In this paper, a characterization of the aperiodicity in existential terms of some state
is given. At the same time, a P system with external output is associated with any
irreducible Markov chain. The designed system provides the aperiodicity of that Markov
chain and spends a polynomial amount of resources with respect to the size of the input.
A formal verification of this solution is presented and a comparative analysis with respect
to another known solution is described.Ministerio de Educación y Ciencia TIN2006–13425Junta de Andalucía P08-TIC-0420
Power factor correction stage and matrix zero voltage switching resonant inverter for domestic induction heating appliances
The technology of flexible cooking surfaces applied to domestic induction heating (IH) appliances offers several advantages that improve the experience of the users, not only because the safety or cleanness, but also due to the fast heating and flexibility. These cooktops have more challenging design requirements because of different mains connections, efficiency requirements, electromagnetic compatibility (EMC) standards, control complexity, and cost. In previous works, the use of a front-end power factor corrector (PFC) rectifier has been proposed to overcome these restrictions. In order to get a cost-effective implementation, this paper proposes the use of a front-end PFC stage and a matrix resonant inverter, which features zero voltage switching (ZVS), to achieve a reduced number of power devices, and get a high performance and reduced power losses in the converter. Finally, an experimental prototype with four outputs of 3.6 kW has been implemented to prove the feasibility of this proposal
Simulating Tritrophic Interactions by Means of P Systems
P systems provide a high level computational modelling framework that combines the structural and dynamical aspects of ecosystems in a compressive and relevant way. The inherent randomness and uncertainty in biological systems is captured by using probabilistic strategies. The design of efficient simulation algorithms in order to reproduce the behavior of these computational models over conventional computers is fundamental for the validation and virtual experimentation processes. In this paper, we describe the modelling framework and two different simulation algorithms. As a case study, a P system based model of an ideal ecosystem with three trophic levels is designed and simulated by both simulation algorithms, providing comparisons of efficiency between them
Comparing simulation algorithms for multienvironment probabilistic P systems over a standard virtual ecosystem
Membrane Computing has recently proved to
be a suitable framework for addressing the modelling of
dynamical biological systems in general, and ecosystems in
particular. Due to the inherent randomness and uncertainty
in biological systems, when designing a model the relevant
tasks to be addressed are the validation and virtual experimentation
processes, rather than the formal verification. It
is therefore crucial to rely on software implementations of
efficient simulation algorithms. This paper presents a
simple (but realistic enough) ecosystem where a carnivore
and several herbivorous species interact. The model of this
ecosystem has been used to compare experimentally the
performance of two different simulation algorithms.Ministerio de Ciencia e Innovación TIN2009–13192Junta de Andalucía P08-TIC-0420
Hierarchical clustering with Membrane Computing.
In this paper we approach the problem of hierarchical clustering through
membrane computing. A specific P system with external output is designed for each
Boolean matrix associated with a finite set of individuals. The computation of the
system allows us to obtain one of the possible classifications in a non-deterministic
way. The amount of resources required in the construction is polynomial in the
number of individuals and of characteristics analyzed.Ministerio de Educación y Ciencia TIN2006-13425Junta de Andalucía TIC-58
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