Hypoxic Cell Waves around Necrotic Cores in Glioblastoma: A Biomathematical Model and its Therapeutic Implications

Glioblastoma is a rapidly evolving high-grade astrocytoma that is distinguished pathologically from lower grade gliomas by the presence of necrosis and microvascular hiperplasia. Necrotic areas are typically surrounded by hypercellular regions known as "pseudopalisades" originated by local tumor vessel occlusions that induce collective cellular migration events. This leads to the formation of waves of tumor cells actively migrating away from central hypoxia. We present a mathematical model that incorporates the interplay among two tumor cell phenotypes, a necrotic core and the oxygen distribution. Our simulations reveal the formation of a traveling wave of tumor cells that reproduces the observed histologic patterns of pseudopalisades. Additional simulations of the model equations show that preventing the collapse of tumor microvessels leads to slower glioma invasion, a fact that might be exploited for therapeutic purposes.Comment: 29 pages, 9 figure

Electrostatic potential variations on stellarator magnetic surfaces in low collisionality regimes

The component of the neoclassical electrostatic potential that is non-constant on the magnetic surface, that we denote by $\tilde\varphi$, can affect radial transport of highly charged impurities, and this has motivated its inclusion in some modern neoclassical codes. The number of neoclassical simulations in which $\tilde\varphi$ is calculated is still scarce, partly because they are usually demanding in terms of computational resources, especially at low collisionality. In this paper the size, the scaling with collisionality and with aspect ratio, and the structure of $\tilde\varphi$ on the magnetic surface are analytically derived in the $1/\nu$, $\sqrt{\nu}$ and superbanana-plateau regimes of stellarators close to omnigeneity; i. e. stellarators that have been optimized for neoclassical transport. It is found that the largest $\tilde\varphi$ that the neoclassical equations admit scales linearly with the inverse aspect ratio and with the size of the deviation from omnigeneity. Using a model for a perturbed omnigeneous configuration, the analytical results are verified and illustrated with calculations by the code KNOSOS. The techniques, results and numerical tools employed in this paper can be applied to neoclassical transport problems in tokamaks with broken axisymmetry.Comment: 30 pages, 12 figures, 1 table. Published versio

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

Fenómenos de retracción y comportamiento frente a la corrosión de materiales base cemento de bajo pH basados en OPC o CAC

Prior to using low-pH cementitious materials in underground repositories for high level waste, the characteristics determining their long-term durability must be analysed in depth. In this sense, different shrinkage tests have been made on mortar and concrete specimens using low-pH cement formulations based on ordinary portland cement (OPC) or calcium aluminate cement (CAC), with high mineral admixtures contents. They showed similar autogenous shrinkage than samples without mineral admixtures but higher drying shrinkage when materials based on OPC with high silica fume contents were considered. Besides, as the use of reinforced concrete could be required in underground repositories, the susceptibility of reinforcement to corrosion when using low-pH cementitious materials based on OPC was analyzed, considering carbon steel and galvanized steel. In the formers corrosion was detected due to the low pore solution pH but any problem was detected when galvanized reinforcement were used.Previo al empleo de materiales con cementos de bajo pH en almacenamientos geológicos profundos (AGP) de residuos radiactivos de alta actividad, características relacionadas con su durabilidad a largo plazo deben ser verificadas. Así, su estabilidad volumétrica se ha analizado en morteros y hormigones de bajo pH basados en OPC o CAC, con elevados contenidos de adiciones minerales. Estos presentaron retracciones autógenas similares a las medidas en materiales convencionales, pero retracciones por secado mayores en los basados en OPC y altos contenidos de humo de sílice. Dado que en zonas de los AGP podría emplearse hormigón armado, también se evaluó la susceptibilidad a la corrosión de aceros al carbono y aceros galvanizados en materiales de bajo pH basados en OPC. Se detectó un inicio temprano de corrosión en los primeros debido al bajo pH presente en el fluido de los poros de estos materiales, sin detectarse problemas al emplear aceros galvanizados

Aluminium and mineral stability in soils from the As Pontes region

[Resumen] Se estudian las fracciones de Al potencialmente liberable de la fase sólida (Al cambiable, potencial lábil y potencial máximo), las formas de Al presentes en disolución de suelo y los índices de saturación para ciertos minerales de Al (gibbsita, gibbsita microcristalina, caolinita, alunita, jurbanita y basaluminita), en horizontes A y B de suelos derivados de diferentes materiales de partida representativos de la zona de estudio (rocas graníticas, neises, esquistos, filit~s, sedimentos cuarzosos y rocas metabásicas). Los resultados muestran que los suelos de granito, filita y neis presentan los mayores niveles de Al cambiable, potencial lábil, potencial máximo y Al total en disolución; los suelos derivados de rocas metabásicas muestran importantes contenidos de Al potencial máximo y escasos nive~s de las formas más lábiles y Al total en disolución. Los esquistos presentan valores intermedios para estas formas de Al. Los índices de saturación mineral indican que, con independencia del material original y tipo de horizonte, un importante número de muestras se sitúan en el campo de la disolución para todos los minerales considerados. Cuando se dan condiciones de sobresaturación, la caolinita es el mineral más estable mientras que la gibbsita es el que más frecuentemente controla la actividad del AP+ en disolución.[Abstract] Al fractions susceptible to be liberated from the solid phase, Al forms in soil solutions and the saturation indexes for certain Al-minerals (gibbsite, microcristaline gibbsite, kaolinite, alunite, jurbanite and basalunite) are studied in the A and B horizonts of soils derived from different parent materials representative of the studied area (granitic rocks, gneisses, schists, phyllites, quarzous sediments and metabasic rocks). The results show that the soils from granite, phyllite and gneiss had the highest levels of exchangeable, labile potential, maximun potential. Al in the solid phase and total Al in soil solution; the soils derived from metabasic rocks showed high quantities of maximun potential Al and low levels of the most labile forms and total Al in solution. The schist displayed intermediate values for these Al forms. The mineral saturation indexes indicate that many samples, independendy of the parent material and horizon type, are situated in the disolution field for the minerals considered. When oversaturation conditions are produced, kaolinite is the most stable mineral and gibbsite the one that, most frequendy, controls AP+ activity in soludo

Contribución al conocimiento de las facies de "Costras calcáreas" del sector oriental de la provincia de Albacete

Se presentan aquí los resultados del estudio de los encostramientos desarrollados en las laderas de la Sierra del Mugrón (provincia de Albacete). Este trabajo pretende ser una aportación al conocimiento de la petrografía de estos materiales, a la vez que un intento de clarificar los criterios que permiten caracterizarlos. La importancia de este estudio viene apoyada por la abundancia de encostramientos calcáreos en un conjunto tan poco discretizado como es el Plio-Cuaternario continental de los paises mediterraneos