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    Numerical computation of Lyapunov matrices for integral delay systems

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    "This paper focuses on the problem of computing Lyapunov matrices for integral delay systems. It is shown that these Lyapunov matrices cannot be computed by means of the existing methods for Lyapunov matrices of differential delay systems. Then, a numerical algorithm for constructing piecewise linear approximations of Lyapunov matrices for integral delay systems is proposed. An example illustrates the procedure.

    Tipos de virus del papiloma humano en cánceres del cérvix, la región anogenital y la cavidad oral en el estado de San Luis Potosí, México

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    Tesis (Doctorado en Ciencias en Biología Molecular)"La infección persistente por virus del papiloma humano (VPH) es necesaria para la transformación irreversible de las células epiteliales hasta Carcinoma Invasor (CI). Hemos determinado la prevalencia de los tipos de VPH en NIA y CI de tumores no cervicales y cervicales para evaluar la oncogenicidad de los tipos virales circulantes en el estado de San Luis Potosí y la prevención potencial de infecciones y lesiones neoplásicas por la vacunación anti-VPH. El estudio incluyó los expedientes y bloques de parafina de carcinomas no cervicales y cervicales diagnosticados en el Hospital Central Ignacio Morones Prieto entre 1999 y 2011. La presencia de VPH fue determinada con el ensayo SPF10-DEIA y los tipos virales identificados con INNO-LiPA. Carcinomas no cervicales. Cinco tipos de alto riesgo (VPH 16, 45, 59, 33 y 35) y dos de bajo riesgo (VPH 11 y 53) fueron identificados. La mayoría de las infecciones fueron por un tipo de alto riesgo y VPH 16 fue el más prevalente. La vagina fue la localización más frecuente de los tumores VPH positivos y la vacunación contra VPH 16 y 18 pudo haber prevenido la mitad de ellos. Carcinomas del cérvix. Entre los 185 expedientes clínicos examinados hubo tres tipos histológicos: carcinoma epidermoide (70.3%), carcinoma adenoescamoso (16.9%) y adenocarcinoma (12.8%). El grupo de 31-60 años incluyó el 76% de los casos y el 74% de pacientes en etapas terminales y defunciones. De 103 bloques de parafina analizados 84 fueron VPH positivos, Identificamos 12 tipos de alto riesgo (VPH 16, 45, 51, 52, 31, 59, 18, 33, 35, 56, 58 y 73), dos de probable alto riesgo (VPH 66 y 53), tres de bajo riesgo (VPH 44, 11 y 70) y dos tipos no clasificados (VPH 69/71 y VPH 74. Concluimos que la mayoría de los carcinomas del cérvix estaba en estadio clínico avanzado. Los tipos más prevalentes son VPH 16 y 45 y la vacuna contra VPH 16 y 18 pudo haber prevenido al menos la mitad de los tumores VPH positivos.""Persistent infection by human papillomavirus (HPV) is necessary for the irreversible transformation of epithelial cells up to high grade intraepitelial neoplasia (HIN) that progresses to invasive carcinoma (IC). We determined the prevalence of HPV types in HIN and IC from non-cervical and cervical tumors to evaluate the oncogenicity ofthe viral types circulating in the state of San Luis Potosí and the potential prevention of infections and neoplastic lesions through anti-HPV vaccination. The study included clinical files and paraffin-embedded tissue blocks from non-cervical and cervical carcinomas diagnosed at Hospital Central Ignacio Morones Prieto between 1999 and 2011. HPV was determined with the SPF10-DEIA assay and the viral types identified with the INNO-LiPA linear array. Non-cervical carcinomas. Five high-risk types (HPV 16, 45, 59, 33 and 35) and two low-risk types (HPV 11 and 54) were. Most infections were by a single HPV high-risk type, the most prevalent being HPV 16. Vagina is the most frequent location of the HPV positive tumors and vaccination against HPV 16 and HPV 18 could have prevented around half of them. Cervical carcinomas. The 185 clinical files examined registered three histological types: epidermoid carcinoma (70.3%), adenosquamous carcinoma (16.9%) and adenocarcinoma (12.8%). The 31-60 years group included 76% of cases and 74% of terminal-stage patients and defunctions. 103 paraffin blocks analyzed 84 of which were HPV positive. We identified 12 high risk types (HPV 16, 45, 51, 52, 31, 59, 18, 33, 35, 56, 58 y 73), two of probable high risk (HPV 66 y 53), three of low risk (HPV 44, 11 y 70) and two unclassified types (HPV 69/71 and HPV 74. We conclude that most cervical carcinomas were advanced. The most prevalent types are HPV 16 and 45, and vaccination against HPV 16 and 18 could have prevented at least half of the HPV positive tumors.

    Efecto de fármacos epigenéticos sobre la inducción de genes de pluripotencia en células somáticas humanas

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    Tesis (Maestría en Ciencias en Biología Molecular)"La generación de células pluripotentes inducidas (iPSCs) por la expresión ectópica de los factores POU5F1 (OCT4), SOX2, KLF4, C-MYC, NANOG y LIN28 ha establecido oportunidades de implementar terapias en el área de medicina regenerativa. Sin embargo, su aplicación clínica está limitada por el uso de vectores virales. Por otro lado, existen fármacos capaces de modificar el epigenoma incrementando la plasticidad celular. El presente trabajo evaluó el efecto de los fármacos epigenéticos sobre la expresión de genes de pluripotencia en células somáticas humanas. Inicialmente, se realizó un ensayo de viabilidad para evaluar la citotoxicidad de los fármacos epigenéticos ácido valproico, hidralazina, talidomida, isotretinoina, ribavirina y azacitidina en una línea celular de fibroblastos dérmicos humanos. Posteriormente, se cultivaron las células humanas en presencia de los fármacos epigenéticos en conjunto con un cóctel de moléculas potenciadoras del proceso de reprogramación. Se comprobó que los fármacos epigenéticos individuales o combinados no causaron una disminución en la viabilidad de los fibroblastos humanos., aunque en combinación con el cóctel de moléculas el efecto citotóxico aumento drásticamente. A consecuencia de esto, se eligió la azacitidina, y el ácido valproico en conjunto con el cóctel de potenciadores de reprogramación con la finalidad de evaluar la expresión de los genes relacionados con la pluripotencia por RT-qPCR. La exposición de los fibroblastos humanos al ácido valproico, azacitidina junto con el cóctel de potenciadores de la reprogramación no fue suficiente para inducir cambios morfológicos, característicos de la transición mesenquimo-epitelio o la activación de los genes relacionados con la pluripotencia. Estos datos sugieren que la modificación de la estructura de la cromatina por el efecto del ácido valproico y azacitidina es solo una parte de una serie de eventos que deben realizarse para inducir la expresión de factores de pluripotencia.""Generation of induced pluripotent stem cells (iPSCs) by ectopic expression of POU5F1 (OCT4), SOX2, KFL4, C-MYC, NANOG and LIN28 has established new opportunities in stem cell research, drug discovery and disease modeling. Nevertheless, genomic integration of viral vectors reduced their clinical applications. On the other hand, there are drugs that increase cell plasticity by modifying the epigenome, among them are valproic acid, hydralazine, thalidomide, isotretinoin, ribavirin and azacytidine. The aim of this study was to evaluate the effect of epigenetic drugs on the expression of pluripotency-related genes in human somatic cells. First, we performed a viability assay to assess the cytotoxicity of the epigenetic drugs in a human cell line. Afterwards, we cultured the human cells in presence of all the epigenetic drugs which we tested. Our results indicate a low cytotoxic effect by the presence of sole and combined epigenetic drugs, although not with the cocktail of reprogramming enhancers. Then, we chose valproic acid, azacytidine, and the cocktail of reprogramming enhancers in order to evaluate the expression of pluripotency-related genes by qPCR. Exposure of the human fibroblasts to valproic acid, azacytidine, and a cocktail of reprogramming enhancers was not enough to induce morphological changes, characteristic of the MET transition, or activation of the pluripotency-related genes. These data suggest, that the modification of the chromatin structure by the effect of valproic acid and azacytidine is only one part of a series of events that must be carried out to induce the expression of pluripotency factors.

    On the kinetic arrest of martensitic transformation in Ni-Mn-In melt-spun ribbons

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    "Kinetic arrest (KA) of martensitic transformation (MT) has been observed in as-solidified Ni52.2Mn34.3In13.5 melt-spun ribbons; a characterization by dc magnetization measurements was carried out. These alloy ribbons transform martensitically from a single austenitic (AST) parent phase with B2-type crystal structure. For an applied magnetic field U0H of 1 T and up to 9 T, a moderate but progressive KA of the MT is observed. The metastability of the non-equilibrium field-cooled glassy state was characterized by introducing thermal and magnetic field fluctuations. It was found that the total magnetization difference (??) between the zero field-cooling (ZFC) and field-cooling (FC) pathways of the temperature dependence of magnetization ??(T) shows irreversible and reversible components; the former decreases as the temperature decreases. After a short thermal annealing of 10 min at 1073 K AST shows a highly ordered L21-type crystal structure and the kinetic arrest of martensitic transformation is no longer observed suggesting a connection between the crystal structure order of austenite and the appearance of the kinetic arrest phenomenon.

    Construcción de secuencias en tándem para análisis de interacción proteína-ADN en herramientas de molécula única

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    Tesis (Maestría en Ciencias en Biología Molecular)"La interacción proteína-ADN tiene un rol determinante en diversos mecanismos biológicos, como son la regulación de la transcripción de genes, la replicación y recombinación sitio específica. Entre las proteínas que llevan a cabo esta función, destacan los factores de transcripción. La gran mayoría de los estudios realizados de la interacción proteína-ADN se han llevado a cabo con estrategias tradicionales, las cuales llegan a enmascarar el comportamiento de moléculas que representen un porcentaje pequeño dentro la muestra. En años recientes, el empleo de herramientas de molécula única, como son la microscopia de fuerza atómica y las pinzas ópticas, ha facilitado el estudio de estas moléculas debido al uso de partículas individuales. El presente trabajo se enfoca en estudiar las proteínas CAP, Clp y SdrP, que pertenecen a la familia CRP/FNR, ampliamente distribuida en bacterias. Estos factores de transcripción tienen la capacidad de interaccionar con los mismos sitios de unión, el sitio de unión nativo del promotor de lactosa (LacNat) y un sitio consenso (CONCAP). Los tres objetivos principales que nos planteamos fueron los siguientes. El diseño y construcción de secuencias repetidas en tándem que contenga los sitios de unión LacNat y CONCAP, para su uso en trabajos posteriores de molécula única. Evaluar la interacción de CAP y SdrP con las secuencias construidas LacNat y CONCAP de un solo repetido, mediante EMSA y DLS. Finalmente, un análisis bioinformático para determinar secuencias ortólogas de Clp con características más favorables para su expresión y purificación. Los resultados constan de la obtención de las construcciones en tándem con dos y tres copias para la secuencia CONCAP y LacNat, respectivamente. La purificación de las proteínas CAP y SdrP, con un rendimiento final de 26 mg y 20 mg por litro de cultivo, respectivamente, y una pureza superior al 90%. Así mismo, los análisis de interacción preliminares indican que CAP y SdrP son capaces de interaccionar con las secuencias CONCAP y LacNat, con un solo repetido. La constante de disociación (Kd) preliminar de SdrP por la secuencia CONCAP fue 0.23 nM y de 0.74 nM para LacNat, ambas estimadas por EMSA. Por último, se seleccionaron 10 ortólogos putativos cuya predicción de éxito en procesos de expresión y purificación fue más favorable, comparada con la secuencia de Xanthomonas campestris que ha sido cristalizada.""The protein-DNA interaction has a determining role in various biological mechanisms, such as the regulation of gene transcription, replication and site-specific recombination. Among the proteins that perform this function, the transcription factors stand out. In bacteria the family of CRP / FNR transcription factors is one of the most widely distributed. Because of the differences in their interaction mechanisms and their structural similarity, we are interested in three members of this family, CAP, Clp and SdrP. These proteins have the ability to interact with the same binding sites, the native lactose promoter binding site (LacNat) and a consensus site designed in the 1980s (CONCAP). The vast majority of studies of the protein-ADN interaction have been carried out with traditional strategies, which come to hide the behavior of molecules representing a small percentage within the sample. In recent years, the use of single-molecule tools, such as atomic force microscopy and optical tweezers, has facilitated the study of these molecules due to the use of individual particles. The three main objectives we proposed were as follows. The design and construction of repeated sequences in tandem containing the LacNat and CONCAP binding sites, for use in subsequent single molecule works. To evaluate the interaction of CAP and SdrP with the sequences constructed LacNat and CONCAP of a single repeated, by EMSA and DLS. Finally, a bioinformatic analysis to determine orthologous sequences of Clp with characteristics more favorable for its expression and purification. Our results show that the tandem integration of two and three copies of CONCAP and LacNat sequences, respectively, were successfully cloned in pBlueScript vector. We obtained protein concentrations of 26 mg and 20 mg per liter of culture for CAP and SdrP, respectively, and a purity greater than 90% for both proteins. Also, preliminary interaction analyzes indicate that CAP and SdrP are capable of interacting with the CONCAP and LacNat sequences when exposed to an individual copy of the binding site. A preliminary dissociation constant (Kd) of of 0.23 nM for CONCAP and 0.74 nM for LacNat was determinated for SdrP transcription factor, estimated by EMSA. Finally, 10 putative orthologues were selected whose prediction of success in expression and purification processes was more favorable.

    2D-DIGE as a strategy to identify serum biomarkers in Mexican patients with Type-2 diabetes with different body mass index

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    "Obesity and type 2 diabetes (T2D) are the most prevalent and serious metabolic diseases affecting people worldwide. However racial and ethnic disparities seems to be a risk factor for their development. Mexico has been named as one of the largest populations with the highest prevalence of diabetes and obesity. The aim of this study was to identify novel T2D-associated proteins in Mexican patients. Blood samples were collected from 62 Mexican patients with T2D and they were grouped according to their body mass index (BMI). A panel of 10 diabetes and obesity serum markers was determined using MAGPIX. A comparative proteomics study was performed using two-dimensional difference in-gel electrophoresis (2D-DIGE) followed by mass spectrometry (LC-MS/MS). We detected 113 spots differentially accumulated, in which 64 unique proteins were identified, proteins that were involved in metabolism pathways, molecular transport, and cellular signalling. Four proteins (14-3-3, ApoH, ZAG, and OTO3) showing diabetes-related variation and also changes in relation to obesity were selected for further validation by western blotting. Our results reveal new diabetes related proteins present in the Mexican population. These could provide additional insight into the understanding of diabetes development in Mexican population and may also be useful candidate biomarkers.

    An upper limit for slow-earthquake zones: self-oscillatory behavior through the Hopf bifurcation mechanism from a spring-block model under lubricated surfaces

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    "The complex oscillatory behavior of a spring-block model is analyzed via the Hopf bifurcation mechanism. The mathematical spring-block model includes Dieterich Ruina's friction law and Stribeck's effect. The existence of self-sustained oscillations in the transition zone where slow earthquakes are generated within the frictionally unstable region is determined. An upper limit for this region is proposed as a function of seismic parameters and frictional coefficients which are concerned with presence of fluids in the system. The importance of the characteristic length scale L, the implications of fluids, and the effects of external perturbations in the complex dynamic oscillatory behavior, as well as in the stationary solution, are take into consideration.

    Geochemistry of komatiites and basalts from the Rio das Velhas and Pitangui greenstone belts, São Francisco Craton, Brazil: Implications for the origin, evolution, and tectonic setting

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    "The Neoarchean Rio das Velhas and Pitangui greenstone belts are situated in the southern São Francisco Craton, Minas Gerais, Brazil. These greenstone belts were formed between ca. 2.79–2.73 Ga, and consist mostly of mafic to ultramafic volcanics and clastic sediments, with minor chemical sediments and felsic volcanics that were metamorphosed under greenschist facies. Komatiites are found only in the Rio das Velhas greenstone belt, which is composed of high-MgO volcanic rocks that have been identified as komatiites and high-Mg basalts, based on their distinctive geochemical characteristics. The Rio das Velhas komatiites are composed of tremolite + actinolite + serpentine + albite with a relict spinifex-texture. The Rio das Velhas komatiites have a high magnesium content ((MgO)adj ? 28 wt.%), an Al-undepleted Munro-type [(Al2O3/TiO2)adj and (CaO/Al2O3)adj] ratio ranging from 27 to 47 and 0.48 to 0.89, relatively low abundances of incompatible elements, a depletion of light rare earth elements (LREE), a pattern of non-fractionated heavy rare- earth elements (HREE), and a low (Gd/Yb)PM ratio (? 1.0). Negative Ce anomalies suggest that alteration occurred during greenschist facies metamorphism for the komatiites and high-Mg basalts. The low [(Gd/Yb)PM 18] and high HREE, Y, and Zr content suggest that the Rio das Velhas komatiites were derived from the shallow upper mantle without garnet involvement in the residue. The chemical compositions [(Al2O3/TiO2)adj, (FeO)adj, (MgO)adj, (CaO/Al2O3)adj, Na, Th, Ta, Ni, Cr, Zr, Y, Hf, and REE] indicate that the formation of the komatiites, high-Mg basalts and basalts occurred at different depths and temperatures in a heterogeneous mantle. The komatiites and high-Mg basalts melted at liquidus temperatures of ~ 1450–1550 °C. The Pitangui basalts are enriched in the highly incompatible LILE (large-ion lithophile elements) relative to the moderately incompatible HFS (high field strength) elements. The Zr/Th ratio ranging from 76 to 213 and the relationship between the Nb/Th and Th/Yb ratios indicate that there is no crustal contamination in the Pitangui greenstone basalts. New multi-dimensional discrimination diagrams and conventional normalized multi-element diagrams indicate an island arc (IA) setting for the komatiites and high-Mg basalts from the Rio das Velhas and a mid ocean-ridge (MOR) to IA setting for the basalts from the Pitangui greenstone belts.

    Efecto magnetocalórico en cintas de los compuestos intermetálicos RNi2 (R= Tb, Dy, Ho, Er) y RAl2 (R= Tb, Dy, Er) obtenidas por solidificación rápida

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    "Varios compuestos intemetálicos en los sistemas binarios RNi2 y RAl2 (R= tierra rara) presentan buenas propiedades magnetocalóricas en el rango de temperatura entre 10 y 80 K, lo que permite su utilización como sustancias refrigerantes para el desarrollo de sistemas de refrigeración para la licuefacción de gases. En el presente trabajo se reporta la obtención y la caracterización de las propiedades magnetocalóricas de los compuestos intermetálicos RNi2 con R= Tb, Dy, Ho, Er, y RAl2 con R= Tb, Dy, Er. Los mismos fueron sintetizados por solidificación rápida usando la técnica de temple rotatorio. Se reportan las curvas de variación de entropía magnética ?SM(T) y variación de temperatura adiabática ?Tad(T), así como la capacidad de refrigeración RC para variaciones de campo magnético ?o?H de 2 y 5 T. Estas se comparan con resultados experimentales y teóricos reportados por otros autores en la literatura para muestras policristalinas en bulto. Se determina el compósito bifásico magnetocalórico con mejores propiedades basado en los compuestos DyNi2 y TbNi2 (0.4(DyNi2) + 0.6(TbNi2)). Los compuestos sintetizados son policristalinos y cristalizan en una estructura cúbica de tipo MgCu2 (C15) propia de las fases de Laves; los parámetros de celda así como la temperatura de Curie son similares a los reportados para muestra en bulto. Las cintas recién solidificadas de los compuestos DyNi2, HoNi2 y ErNi2 presentaron valores superiores de |?SMpeak| según la dirección longitudinal con respecto a lo reportado para aleaciones policristalinas en bulto. Esto resulta de la combinación de la anisotropía de la magnetización que presentan estos materiales con la textura cristalográfica que se obtiene como resultado de la técnica de síntesis empleada. En estos casos, las cintas están formadas por granos con su eje principal de crecimiento perpendicular al plano de las cintas por lo que el eje de fácil magnetización queda con cierta orientación preferencial según la dirección longitudinal de formación de la cinta.""Several intermetallic compounds in the RNi2 and RAl2 binary systems (R= rare earth), shows good MC properties as magnetic refrigerants in the temperature range 10-80 K; this allows their use as magnetic refrigerants for the development of magnetic refrigerators for gases liquefaction. Present work, focuses on the synthesis and characterization of the magnetocaloric properties of the intermetallic compounds RNi2 with R= Tb, Dy, Ho, Er, and RAl2 with R= Tb, Dy, Er. They were synthesized by rapid solidification using the melt spinning technique. The thermal dependence of the magnetic entropy change ?SM(T) and adiabatic temperature change ?Tad(T) curves, as well as the refrigerant capacity (RC) for magnetic field changes ?o?Hmax of 2 and 5 T are reported. They are compared with the theoretical and experimental results reported for bulk polycrystalline samples in literature by other authors. The two-phase composite with the best magnetocaloric properties based on the DyNi2 and TbNi2 compounds is (0.4(DyNi2) + 0.6(TbNi2)) is reported. The melt-spun ribbons of the compounds produced are polycrystalline and crystallize into the cubic MgCu2-type structure (C15) of the Laves phases; the cell parameters and the Curie temperature are similar to those reported for bulk polycrystalline alloys. For as-solidified ribbons of the DyNi2, HoNi2 and ErNi2 compounds we found showed superior |?SMpeak| values with respect to the reported for bulk polycrystalline alloys along the longitudinal direction. This enhanced MC response along ribbon longitudinal direction results from the combination of the distinct anisotropic magnetization of these materials with the crystallographic texture induced by the fabrication method employed. In these cases, the ribbons are formed by columnar in shape grains with their longer axes perpendicular to ribbon plane; then the easy axis magnetization shows preferential orientation along the rolling direction.

    Potential fields modeling of the Serdan Oriental basin, Eastern Mexico

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    "In the eastern portion of the Trans-Mexican Neovolcanic Belt a group maars, rhyolitic domes, and cinder cones are scattered within the Oriental-Serdán basin. They are flanked by large polygenetic volcanoes. We use aeromagnetic and gravimetric fields to infer and model the main anomalies in the region, with the objective of identifying and characterizing the sub-surface sources of the volcanic activity. A large, positive magnetic anomaly overlaps the principal area of volcanic activity; it coincides with the main, positive gravimetric anomaly in the area. Both 2-D and 3-D gravity, as well as magnetic models confirm the existence of a large, dense, and magnetized intrusion body nearly reaching the surface, inferred to be the source of the observed anomalies. The intrusion is flanked to the south by rhyolitic domes. Three independently modeled cross-sections coincide in correlating the presence of maars with upward projections of the main intrusion; these projections we interpret as diatreme-type structures, although the modeling scale does not allow for individual identifications. The conduit that supplied magma for the emplacement of the rhyolitic domes of Las Derrumbadas is also identified to depths of four kilometers. A gravity inversion shows in 3-D space the density distribution at various density ranges.

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