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

Coupling single molecule magnets to quantum circuits

In this work we study theoretically the coupling of single molecule magnets (SMMs) to a variety of quantum circuits, including microwave resonators with and without constrictions and flux qubits. The main results of this study is that it is possible to achieve strong and ultrastrong coupling regimes between SMM crystals and the superconducting circuit, with strong hints that such a coupling could also be reached for individual molecules close to constrictions. Building on the resulting coupling strengths and the typical coherence times of these molecules (of the order of microseconds), we conclude that SMMs can be used for coherent storage and manipulation of quantum information, either in the context of quantum computing or in quantum simulations. Throughout the work we also discuss in detail the family of molecules that are most suitable for such operations, based not only on the coupling strength, but also on the typical energy gaps and the simplicity with which they can be tuned and oriented. Finally, we also discuss practical advantages of SMMs, such as the possibility to fabricate the SMMs ensembles on the chip through the deposition of small droplets.Comment: 23 pages, 12 figure

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

Cochleates derived from Vibrio cholerae O1 proteoliposomes : The impact of structure transformation on mucosal immunisation

Cochleates are phospholipid-calcium precipitates derived from the interaction of anionic lipid vesicles with divalent cations. Proteoliposomes from bacteria may also be used as a source of negatively charged components, to induce calcium-cochleate formation. In this study, proteoliposomes from V. cholerae O1 (PLc) (sized 160.7±1.6 nm) were transformed into larger (16.3±4.6 µm) cochleate-like structures (named Adjuvant Finlay Cochleate 2, AFCo2) and evaluated by electron microscopy (EM). Measurements from transmission EM (TEM) showed the structures had a similar size to that previously reported using light microscopy, while observations from scanning electron microscopy (SEM) indicated that the structures were multilayered and of cochleate-like formation. The edges of the AFCo2 structures appeared to have spaces that allowed penetration of negative stain or Ovalbumin labeled with Texas Red (OVA-TR) observed by epi-fluorescence microscopy. In addition, freeze fracture electron microscopy confirmed that the AFCo2 structures consisted of multiple overlapping layers, which corresponds to previous descriptions of cochleates. TEM also showed that small vesicles co-existed with the larger cochleate structures, and in vitro treatment with a calcium chelator caused the AFCo2 to unfold and reassemble into small proteoliposome-like structures. Using OVA as a model antigen, we demonstrated the potential loading capacity of a heterologous antigen and in vivo studies showed that with simple admixing and administration via intragastric and intranasal routes AFCo2 provided enhanced adjuvant properties compared with PLc

Anti-Ro52/TRIM21 antibodies are associated with aberrant inflammatory circuits in patients with systemic autoimmune rheumatic diseases

INTRODUCTION: Anti-Ro52/TRIM21 antibodies are markers for several systemic autoimmune rheumatic diseases (SARD). OBJECTIVE: To assess whether anti-Ro52/TRIM21 antibodies are related to abnormalities in inflammatory circuits. METHODS: Cross-sectional study of consecutive outpatients with SARD. Anti-Ro52/TRIM21 antibodies and serum amyloid A protein were measured by ELISA; panels for 18 cytokines and nine chemokines were analyzed on a Luminex reading platform, while high-sensitivity C-reactive protein (hs-CRP) and complement were measured by nephelometry. RESULTS: Among 167 included patients, 143 had systemic lupus erythematosus (SLE), 16 had primary Sjögren's syndrome and eight had systemic sclerosis; 41 (24%) were positive for anti-Ro52/TRIM21 antibodies. Patients with anti-Ro52/TRIM21 antibodies had higher serum levels of IL-2, IL-4, IL-6, GM-CSF, IL-21, IL-22, hs-CRP and chemokines CCL4, CXCL8, CXCL10 and CXCL12, but lower levels of complement C4. Anti-Ro52/TRIM21 antibody titers were positively correlated with IL-2, IL-4, IL-6, IL-10, IL-21, IL-22, CXCL10, and hs-CRP, and negatively with complements C3 and C4. When only SLE patients were included, no association was identified between anti-Ro52/TRIM21 antibodies and disease activity or organ-specific involvement. CONCLUSIONS: Anti-Ro52/TRIM21 antibodies are associated with aberrant cytokine circuits and elevated levels of angiogenic molecules and neutrophil and monocyte chemoattractants, which suggests an active role for these antibodies in SARD.</p

Las zonas arqueológicas como paisajes culturales: el parque arqueológico de Las Médulas(León)

Sin resume

Mandibular odontogenic myxoma : reconstructive considerations by means of the vascularized fibular free flap

The odontogenic myxoma is a rare entity located in mandible and upper maxilla. Due to its local aggressiveness, wide surgical excision is mandatory. Several surgical techniques have been described for the reconstruction of segmental mandibular defects. In comparison with other free flaps, the vascularized free fibular flap (VFFF) supports the longest amount of bone and, due to the nature of the vascular supply a complete freedom in location of the osteotomy is present. A precise mandibular arc can be performed following bone resection. We suggest the performance of the ?in situ? VFFF technique in order to recreate mandibular contour by means of several osteotomies, while the pedicle is still attached to the leg. Substantial decrease in surgical time is obtained. With the ?double-barrel? technique and subsequent osseointegrated implants, good results are obtained in the reconstruction of dentate patients without maxillary atrophy. We present two new cases of large odontogenic mandibular myxoma. Wide surgical excision by means of hemimandibulectomies and subsequent reconstruction with VFFF were performed

Empirical Comparison of Graph-based Recommendation Engines for an Apps Ecosystem

Recommendation engines (RE) are becoming highly popular, e.g., in the area of e-commerce. A RE offers new items (products or content) to users based on their profile and historical data. The most popular algorithms used in RE are based on collaborative filtering. This technique makes recommendations based on the past behavior of other users and the similarity between users and items. In this paper we have evaluated the performance of several RE based on the properties of the networks formed by users and items. The RE use in a novel way graph theoretic concepts like edges weights or network flow. The evaluation has been conducted in a real environment (ecosystem) for recommending apps to smartphone users. The analysis of the results allows concluding that the effectiveness of a RE can be improved if the age of the data, and if a global view of the data is considered. It also shows that graph-based RE are effective, but more experiments are required for a more accurate characterization of their properties

Influence of Surface Chemistry on the Electrochemical Performance of Biomass-Derived Carbon Electrodes for its Use as Supercapacitors

The following are available online at https://www.mdpi.com/1996-1944/12/15/2458/s1, Figure S1. N2 adsorption and desorption isotherms at 77K of CK-series samples. Figure S2: High resolution XPS deconvoluted spectra in the corresponding regions: (a) C1s, (b) O1s, (c) N1s and (d) S2p3/2 for the activated carbons prepared from Custard apple tree wood (CK-Serie). Figure S3: High resolution XPS deconvoluted spectra in the corresponding regions: (a) C1s, (b) O1s, (c) N1s and (d) S2p3/2 for the activated carbons prepared from Fig tree wood (FK-Serie). Figure S4: High resolution XPS deconvoluted spectra in the corresponding regions: (a) C1s, (b) O1s, (c) N1s and (d) S2p3/2 for the activated carbons prepared from Olive tree wood (OK-Serie).first_page settings Open AccessFeature PaperArticle Influence of Surface Chemistry on the Electrochemical Performance of Biomass-Derived Carbon Electrodes for its Use as Supercapacitors by Abdelhakim Elmouwahidi 1 [OrcID] , Esther Bailón-García 1, Luis A. Romero-Cano 2 [OrcID] , Ana I. Zárate-Guzmán 3, Agustín F. Pérez-Cadenas 1,* [OrcID] and Francisco Carrasco-Marín 1 [OrcID] 1 Research Group in Carbon Materials, Inorganic Chemistry Department, Faculty of Sciences, University of Granada, Campus Fuente Nueva s/n. 18071 Granada, Spain 2 Facultad de Ciencias Químicas, Universidad Autónoma de Guadalajara, Av. Patria 1201, Zapopan, Jalisco C. P. 45129, Mexico 3 Centro de Investigación y Desarrollo Tecnológico en Electroquímica (CIDETEQ) S.C., Parque Tecnológico Sanfandila, Pedro Escobedo, Querétaro 760703, Mexico * Author to whom correspondence should be addressed. Materials 2019, 12(15), 2458; https://doi.org/10.3390/ma12152458 Received: 28 June 2019 / Revised: 31 July 2019 / Accepted: 1 August 2019 / Published: 2 August 2019 (This article belongs to the Special Issue Element-Doped Functional Carbon-based Materials) Download PDF Browse Figures Cite This Paper Abstract Activated carbons prepared by chemical activation from three different types of waste woods were treated with four agents: melamine, ammonium carbamate, nitric acid, and ammonium persulfate, for the introduction of nitrogen and oxygen groups on the surface of materials. The results indicate that the presence of the heteroatoms enhances the capacitance, energy density, and power density of all samples. The samples treated with ammonium persulfate show the maximum of capacitance of 290 F g−1 while for the melamine, ammonium carbamate, and nitric acid treatments, the samples reached the maximum capacitances values of 283, 280, and 455 F g−1 respectively. This remarkable electro-chemical performance, as the high specific capacitances can be due to several reasons: i) The excellent and adequate textural characteristics makes possible a large adsorption interface for electrolyte to form the electrical double layer, leading to a great electrochemical double layer capacitance. ii) The doping with hetero-atoms enhances the surface interaction of these materials with the aqueous electrolyte, increasing the accessibility of electrolyte ions. iii) The hetero-atoms groups can also provide considerable pseudo-capacitance improving the overall capacitance.This work was supported by FEDER and Spanish MINECO (grant number CTQ-2013-44789-R); and Junta de Andalucía (grant numbers P12-RNM-2892, RNM172)