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

El tamp en valencià

This essay intends to apply to the Valencian verb the linguistic method of TAMP (tense-aspect-mood-person) within which different pragmatic parameters are organized in such a way never before seen to better understand this phenomena. The basic theory that this application shows is the Topological-Natural Pragmatics (T-NP, Calvo 1989) in which the tense-aspect relationship is dominated by the super-structural mood-person relationship. In this way, a new verbal paradigm is offered to explain the necessity of the past periphrastic or of the marked first person of the present indictive. The explanation of TAMP in Valencian is based in morphology, since there exists morphems which characterize it: stress (—'(—), —(—')), aspect (-av-I-i-), mood (- Vr-) and supermood (-Vs-). When the morphems do not appear, the result is a general background that permits different verbal uses and their neutralizations

Flow Blurring-Enabled Production of Polymer Filaments from Poly(ethylene oxide) Solutions

Flow blurring (FB) atomizers are relatively simple yet robust devices used for the generation of sprays from solutions of a wide range of viscosities. In this work, we have demonstrated that FB devices may also be applied for massive production of liquid filaments from polymeric solutions. They can later be transformed into solid filaments and fibers, leading to the production of so-called fiber mats. The liquid precursors consisted of poly(ethylene oxide) (PEO) solutions of varying molecular weights (105 [100k] to 4 × 106 g/mol [4M]) and concentrations. The FB device was operated in the gas pressure range of 3−6 bar. Except for solutions of PEO 100k, all solutions exhibited a shear thinning behavior. For massive filament production, a threshold polymer concentration (ct) was identified for each molecular weight. Below such concentration, the atomization resulted in droplets (the classical FB functioning mode). Such a threshold value decreased as the PEO molecular weight increased, and it coincides with the polymer coil overlap concentration, c*. The viscoelastic nature of the solutions was also observed to increase with the molecular weight. A 3.2 dependency of the zero-shear rate viscosity on a so-called Bueche parameter was found for filament production, whereas a nearly linear dependency was found for droplet production. In general, the mean diameter of the filaments decreased as they traveled downstream from the atomization point. Furthermore, at a given distance from the atomizer outlet and gas pressure, the mean filament diameter slightly shifted toward larger sizes with increasing PEO molecular weight. The tendency agrees well with the calculated filaments’ Deborah number, which increases with PEO molecular weight. The approach presented herein describes a highthroughput and efficient method for the massive production of viscous filaments. These may be transformed into fibers by an on-line drying step.Ministerio de Economía y Competitividad DPI2016-78887-C3-1-

Evaluation of a microbial muramidase supplementation on growth performance, apparent ileal digestibility, and intestinal histology of broiler chickens

The current study evaluated the effects of different inclusion levels of microbial muramidase (Muramidase 007, DSM Nutritional Products) on gastrointestinal functionality by determination of apparent ileal digestibility (AID) of nutrients, investigation of intestinal histomorphology, and quantification of resulting growth performance. Four maize-wheat-soybean experimental diets were produced without (C) and with different dosages of muramidase: low (L, 25,000 LSU(F)/kg), medium (M, 35,000 LSU(F)/kg), and high (H, 45,000 LSU(F)/kg); diets were fed to broilers for 35 d. At the end of the experiment, AID of ether extract (EE), crude protein (CP), Ca, and P were determined and samples of the mid-jejunum and -ileum were collected for histomorphological observations. Data were subjected to ANOVA analysis using the GLM procedure. Orthogonal polynomial contrasts were used to assess linear and quadratic effects of different levels of the muramidase. At the end of the trial, Muramidase 007 supplementation linearly increased body weight gain and decreased feed conversion ratio (FCR) (P ≤ 0.05). Adding the muramidase to broiler diets also linearly increased the European poultry efficiency factor (P ≤ 0.05). Inclusion of the muramidase in broiler diets linearly increased AID of CP, EE, and P (P ≤ 0.05), and the H group had a higher AID of EE and CP compared to C group (P ≤ 0.05). Microbial muramidase supplementation linearly increased ileal villus length to crypt depth ratio and decreased the number of ileal CD45 cells (P ≤ 0.05). Broilers fed M and H diets had fewer number of CD45 cells in the ileum compared to those in C group (P ≤ 0.05). In conclusion, the results of the present study demonstrated that inclusion of the microbial muramidase in broiler diets could increase AID of key nutrients and improve growth performance in broilers. Adding microbial muramidase to broiler diets can therefore be considered as an interesting prospect to improve gastrointestinal functionality. Biological mechanisms causing these improvements need to be studied further

Emeralds from the Delbegetey deposit (Kazakhstan): mineralogical characteristics and fluid-inclusion study

The aim of this study is to provide the first detailed mineralogical and fluid-inc1usion description of emeralds from the Delbegetey deposit (Kazakhstan). The characteristic features of Delbegetey emeralds are established: they have dissolution figures on crystal faces, bluish colour and distinct colour zoning; the refractive indices are ro = 1.566-1.570, E = 1.558-1.562, and the specific gravity is 2.65±0.005, relatively low for natural emeralds; they have very small concentrations of the impurities (Fe, Mg, Na and others) typical of other emeralds, and contain Cr and V; there is a significant preponderance of vapour in fluid inc1usions of all types and there is liquid-to-vapour homogenization of primary fluid inc1usions (at 395-420°C). The lattice oxygen isotope composition data obtained (0180 SMOW value of 11.3%0) situate the deposit within the range characteristic of other granite-related emerald deposits. Emerald crystallization took place in low-density (0.40-0.55 g/cm3 ) aqueous fluid, with the following chemical composition (mol.%): 75.6-97.4 HzO, 0.0-18.4 caz, 0.0-0.9 C~, and 4.06-9.65 wt.% NaCI equiv. salinity. According to the calculated isochores, the pressure offormation ofthe Delbegetey emeralds can be estimated at 570-1240 bar

Regional cohesion in the EU: An analysis using the Lisbon index approach

El Índice Regional de Lisboa (IRL) cuantifica la cohesión y sintetiza en un solo valor la distancia de las regiones europeas respecto a los objetivos de la Estrategia de Lisboa, así como la distancia existente entre ellas. El IRL se ha calculado para 265 regiones con información procedente de Eurostat sobre el mercado laboral, la formación y el gasto en I+D+i en el periodo 2000-2010. Los resultados muestran que en la EU-27 se consiguió mejorar la situación de las regiones hasta 2007, pero la crisis ha producido un aumento de las desigualdades, situación de la que no escapan las regiones españolas.The Regional Lisbon Index (RLI) quantifies cohesion and summarizes into a single value the distance of European regions to the objectives of the Lisbon Strategy and the distance between them. The RLI has been calculated for 265 European NUTS2 with information from Eurostat on the labor market, training and R & D, in the period 2000-2010. Results show that the regional situation improved up in the EU-27 to 2007, but the crisis has been an increased in inequality, a situation that also occurs in the Spanish regions.Publishe

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