Development of a three-dimensional bone-like construct in a soft self-assembling Peptide matrix

This work describes the development of a three-dimensional (3D) model of osteogenesis using mouse preosteoblastic MC3T3-E1 cells and a soft synthetic matrix made out of self-assembling peptide nanofibers. By adjusting the matrix stiffness to very low values (around 120 Pa), cells were found to migrate within the matrix, interact forming a cell-cell network, and create a contracted and stiffer structure. Interestingly, during this process, cells spontaneously upregulate the expression of bone-related proteins such as collagen type I, bone sialoprotein, and osteocalcin, indicating that the 3D environment enhances their osteogenic potential. However, unlike MC3T3-E1 cultures in 2D, the addition of dexamethasone is required to acquire a final mature phenotype characterized by features such as matrix mineralization. Moreover, a slight increase in the hydrogel stiffness (threefold) or the addition of a cell contractility inhibitor (Rho kinase inhibitor) abrogates cell elongation, migration, and 3D culture contraction. However, this mechanical inhibition does not seem to noticeably affect the osteogenic process, at least at early culture times. This 3D bone model intends to emphasize cell-cell interactions, which have a critical role during tissue formation, by using a compliant unrestricted synthetic matrix

Interacción de los antineoplásicos orales con los alimentos: revisión sistemática

[email protected]ón: Los estudios de biodisponibilidad son parte integrante del desarrollo clínico de medicamentos para administración oral con el fin de identificar potenciales interacciones fármaco-alimento (iFA). Actualmente, para los antineoplásicos orales se empieza a reconocer su importancia clínica, aun cuando lamentablemente, la información disponible presenta variabilidad en su evidencia científica. Objetivos: Revisar la evidencia científica disponible sobre las interacciones de los alimentos con medicamentos antineoplásicos orales y establecer recomendaciones para su administración. Métodos: Se realizó una búsqueda bibliográfica en Medline y The Cochrane Library para el periodo comprendido entre enero de 1966 a marzo de 2008, enfocada a identificar las publicaciones sobre interacciones fármaco alimento con antineoplásicos orales. El análisis bibliográfico consta de dos fases. En la primera fase se excluyeron los artículos que por título y contenido del resumen no se correspondían con el objetivo planteado; en la segunda fase se eliminaron las referencias duplicadas en ambas bases de datos. Los criterios de inclusión para seleccionar los artículos fueron: diseño (revisiones sistemáticas, metaanálisis, ensayos clínicos randomizados Fase I y II), población (pacientes adultos; >19 años de edad), intervención evaluada (administración de antineoplásicos orales bajo condiciones de ayuno o con alimentos) y medida del resultado de la iFA (cálculo del IC90% de la razón entre la media geométrica de valores del área bajo la curva de concentraciones plasmáticas (ABC) o la concentración plasmática máxima (Cmax) con y sin alimentos). Se excluyeron las publicaciones que como medida de resultado no hacían referencia al dictamen de bioequivalencia establecido por la Food and Drugs Administration (FDA). La valoración crítica de los artículos seleccionados se realizó según las recomendaciones que de acuerdo con la FDA deben cumplir estos estudios. Resultados: En la búsqueda inicial se obtuvieron 850 referencias (98,5% Medline + y 1,4% Cochrane). En la primera fase se excluyeron el 87,7% (746) de los artículos, correspondiendo el 100% a la búsqueda en Medline. En la segunda fase, quedaron 40 artículos (5,2% de los iniciales) para su lectura crítica a texto completo, a los que se añadieron cuatro más no indexados en Medline. De la lectura crítica de los 44 artículos finales, se excluyeron 25 artículos (20 artículos originales, 4 comunicaciones cortas y 1 metanálisis) por no incluir como medida de resultado el dictamen de bioequivalencia. Los 19 (2,2%) artículos restantes proporcionaron información sobre 19 fármacos antineoplásicos orales, en 210 pacientes y 146 voluntarios sanos. De estos 19 fármacos, el 63% no presentan iFA o interacciones fármaco-alimento, pudiéndose administrar indistintamente con/sin alimentos; el 21% se deben administrar con alimentos y sólo el 16% presentan interacción fármaco alimento, por lo que se deben administrar sin alimentos. Discusión: Actualmente, la importancia clínica de las interacciones fármaco alimento con antineoplásicos orales se identifica más directamente con la seguridad del paciente que con la efectividad del tratamiento. Ante el desarrollo de estos agentes orales, su irrupción en la terapia oncológica desplazando a la terapia parenteral, con costes mensuales de miles de euros, hay necesidad de realizar estudios farmacocinéticos y farmacodinámicos bien diseñados. Su objetivo debe de ser comparar su biodisponibilidad en presencia o ausencia de alimentos con la respuesta clínica. Mientras tanto, establecer recomendaciones para su administración en relación con los alimentos, es inconsistente para algunos de estos fármacos y su resultado incierto por la falta de estudios fundamentados en el dictamen de bioequivalencia establecido por la FDA.Introduction: studies on bioavailability are part of the clinical development of drugs for oral use in order to identify potential drug-food interactions. For oral antitumor drugs, their clinical importance is currently recognized although regrettably the information available presents variability concerning the scientific evidence. Objectives: To review the available scientific evidence about oral anti-tumor medications and establish the recommendations for their administration with foods. Methods: We carried out a bibliographic search in Medline and The Cochrane Library for the period January of 1966 to March of 2008, focused on identifying those publications about drug-food interactions with oral antitumor medications. The bibliographical analysis was made in two steps. During the first phase, we excluded those articles in which the title or their content did not correspond with the objective settled; during the second phase, we deleted all the references duplicated in both databases. The inclusion criteria to select the articles were: design (systematic reviews, meta-analysis, Phase I and Phase II randomized clinical trials), population (adult patients; >19 years of age), intervention evaluated (administration of oral anti-tumor drugs under fasting conditions or with food) and measurement of the iFA results (calculation of the 90% CI of the odds ratio between the geometric mean of the values under the curve of the plasma concentrations (ABC) or the maximal plasma concentration (Cmax) with and without foods). We excluded those publications that did not make reference to the bioequivalence dictamen established by the Food and Drugs Administration (FDA) in their outcomes measurement. A critical appraisal of the selected articles was done according to the recommendations that the FDA established to be met by these studies. Results: At the initial search we obtained 850 references (98.5% Medline + and 1.4% Cochrane). During the first phase, we excluded 87.7% (746) of the articles, 100% of them corresponding to the search in Medline. During the second phase, 40 studies remained (5.2% of the initial ones) for full-text critical appraisal, to which four studies were added not indexed in Medline. From the critical appraisal of the 44 final articles, 25 were excluded (20 original articles, 4 short communications, and 1 meta-analysis) because they did not include as an outcome measure the bioequivalence dictamen. The 19 (2.2%) remaining articles provided information on 19 oral anti-tumor drugs in 210 patients and 146 healthy volunteers. Of these 19 drugs, 63% did not present drugfood interactions, with the possibility of administering them either with or without food; 21% have to be administered with foods and only 16% present drug-food interactions, so they have to be administered without foods. Discussion: Currently, the clinical importance of drugfood interactions with oral anti-tumor drugs is identified more directly with the patient's safety than with the efficacy of the therapy. Given the development of these oral agents, their incorporation into the oncologic strategy displacing parenteral therapy, with monthly costs of thousands of Euros, it is necessary to perform well-designed studies on pharmacokinetics and pharmacodynamics. Their goal has to be comparing their bioavailability in the presence or absence of foods with the clinical response. In the meanwhile, to establish recommendations for their administration in relation to foods is inconsistent for some of these drugs and their results is uncertain given the lack of studies based on the FDAbioequivalence dictamen

Definición de concepto de paneles desplegables para microsatelites

Los sistemas de generación de energía de microsatélites se basan en general, por consideraciones de complejidad y costo, en paneles solares fijos adheridos al cuerpo de los mismos. Las limitaciones en sus dimensiones externas implican severas restricciones de potencia disponible. Se resumen aquí los estudios realizados por un grupo de alumnos y profesionales del Instituto Universitario Aeronáutico (IUA) tendientes a dotar de paneles desplegables a microsatélites con mayor requerimiento de potencia. Se efectuó la definición conceptual de un sistema de paneles desplegables para ser adaptado al μSAT I “Víctor”. Para ello se debieron investigar distintos aspectos teórico-prácticos e implementar los algoritmos y procedimientos de cálculo pertinentes, lo que le dio valor educativo. Los principales puntos desarrollados, son: selección de configuración geométrica, estudio térmico y de generación eléctrica, y definición del perfil tecnológico. Se realizaron ensayos de componentes y materiales para complementar los estudios teóricos, construyéndose además un demostrador tecnológico.Power systems for microsatellites, are generaly based on solar cells arrays mounted to the cover of the satellite, because of considerations on price and complexity. The limitations in size, cause severe restriccion on power avaliability. Studies carried out by teachers and pupils of the IUA aiming to the use of deployable solar cell array system in a microsatellite, are resumed here. Concept definition of a deployable solar panel assembly to be adapted to the μSAT I “Victor” was performed. For this, theoretical and practical methodes were investigated in order to adopt algoritms and procedures resulting very valuable for educational purposes. The main aspects studied, were: panel array confuguration, thermal and electrical behavior and technological definition. Several tests on parts and materials were made in order to complement theroetical studies and finally, a technological demonstrator was constructed.Tema 4: Energía solar y conversión fotovoltaica.Asociación Argentina de Energías Renovables y Medio Ambiente (ASADES

Definición de concepto de paneles desplegables para microsatelites

Los sistemas de generación de energía de microsatélites se basan en general, por consideraciones de complejidad y costo, en paneles solares fijos adheridos al cuerpo de los mismos. Las limitaciones en sus dimensiones externas implican severas restricciones de potencia disponible. Se resumen aquí los estudios realizados por un grupo de alumnos y profesionales del Instituto Universitario Aeronáutico (IUA) tendientes a dotar de paneles desplegables a microsatélites con mayor requerimiento de potencia. Se efectuó la definición conceptual de un sistema de paneles desplegables para ser adaptado al μSAT I “Víctor”. Para ello se debieron investigar distintos aspectos teórico-prácticos e implementar los algoritmos y procedimientos de cálculo pertinentes, lo que le dio valor educativo. Los principales puntos desarrollados, son: selección de configuración geométrica, estudio térmico y de generación eléctrica, y definición del perfil tecnológico. Se realizaron ensayos de componentes y materiales para complementar los estudios teóricos, construyéndose además un demostrador tecnológico.Power systems for microsatellites, are generaly based on solar cells arrays mounted to the cover of the satellite, because of considerations on price and complexity. The limitations in size, cause severe restriccion on power avaliability. Studies carried out by teachers and pupils of the IUA aiming to the use of deployable solar cell array system in a microsatellite, are resumed here. Concept definition of a deployable solar panel assembly to be adapted to the μSAT I “Victor” was performed. For this, theoretical and practical methodes were investigated in order to adopt algoritms and procedures resulting very valuable for educational purposes. The main aspects studied, were: panel array confuguration, thermal and electrical behavior and technological definition. Several tests on parts and materials were made in order to complement theroetical studies and finally, a technological demonstrator was constructed.Tema 4: Energía solar y conversión fotovoltaica.Asociación Argentina de Energías Renovables y Medio Ambiente (ASADES

Definición de concepto de paneles desplegables para microsatelites

Los sistemas de generación de energía de microsatélites se basan en general, por consideraciones de complejidad y costo, en paneles solares fijos adheridos al cuerpo de los mismos. Las limitaciones en sus dimensiones externas implican severas restricciones de potencia disponible. Se resumen aquí los estudios realizados por un grupo de alumnos y profesionales del Instituto Universitario Aeronáutico (IUA) tendientes a dotar de paneles desplegables a microsatélites con mayor requerimiento de potencia. Se efectuó la definición conceptual de un sistema de paneles desplegables para ser adaptado al μSAT I “Víctor”. Para ello se debieron investigar distintos aspectos teórico-prácticos e implementar los algoritmos y procedimientos de cálculo pertinentes, lo que le dio valor educativo. Los principales puntos desarrollados, son: selección de configuración geométrica, estudio térmico y de generación eléctrica, y definición del perfil tecnológico. Se realizaron ensayos de componentes y materiales para complementar los estudios teóricos, construyéndose además un demostrador tecnológico.Power systems for microsatellites, are generaly based on solar cells arrays mounted to the cover of the satellite, because of considerations on price and complexity. The limitations in size, cause severe restriccion on power avaliability. Studies carried out by teachers and pupils of the IUA aiming to the use of deployable solar cell array system in a microsatellite, are resumed here. Concept definition of a deployable solar panel assembly to be adapted to the μSAT I “Victor” was performed. For this, theoretical and practical methodes were investigated in order to adopt algoritms and procedures resulting very valuable for educational purposes. The main aspects studied, were: panel array confuguration, thermal and electrical behavior and technological definition. Several tests on parts and materials were made in order to complement theroetical studies and finally, a technological demonstrator was constructed.Tema 4: Energía solar y conversión fotovoltaica.Asociación Argentina de Energías Renovables y Medio Ambiente (ASADES

Emergence of Toscana Virus in Europe

In southern Europe, Toscana virus is one of the three leading causes of aseptic meningitis

The Tate conjecture for K3 surfaces over finite fields

Artin's conjecture states that supersingular K3 surfaces over finite fields have Picard number 22. In this paper, we prove Artin's conjecture over fields of characteristic p>3. This implies Tate's conjecture for K3 surfaces over finite fields of characteristic p>3. Our results also yield the Tate conjecture for divisors on certain holomorphic symplectic varieties over finite fields, with some restrictions on the characteristic. As a consequence, we prove the Tate conjecture for cycles of codimension 2 on cubic fourfolds over finite fields of characteristic p>3.Comment: 20 pages, minor changes. Theorem 4 is stated in greater generality, but proofs don't change. Comments still welcom

Investigation of conduction band structure, electron scattering mechanisms and phase transitions in indium selenide by means of transport measurements under pressure

In this work we report on Hall effect, resistivity and thermopower measurements in n-type indium selenide at room temperature under either hydrostatic and quasi-hydrostatic pressure. Up to 40 kbar (= 4 GPa), the decrease of carrier concentration as the pressure increases is explained through the existence of a subsidiary minimum in the conduction band. This minimum shifts towards lower energies under pressure, with a pressure coefficient of about -105 meV/GPa, and its related impurity level traps electrons as it reaches the band gap and approaches the Fermi level. The pressure value at which the electron trapping starts is shown to depend on the electron concentration at ambient pressure and the dimensionality of the electron gas. At low pressures the electron mobility increases under pressure for both 3D and 2D electrons, the increase rate being higher for 2D electrons, which is shown to be coherent with previous scattering mechanisms models. The phase transition from the semiconductor layered phase to the metallic sodium cloride phase is observed as a drop in resistivity around 105 kbar, but above 40 kbar a sharp nonreversible increase of the carrier concentration is observed, which is attributed to the formation of donor defects as precursors of the phase transition.Comment: 18 pages, Latex, 10 postscript figure

Spider silk gut: Development and characterization of a novel strong spider silk fiber

Spider silk fibers were produced through an alternative processing route that differs widely from natural spinning. The process follows a procedure traditionally used to obtain fibers directly from the glands of silkworms and requires exposure to an acid environment and subsequent stretching. The microstructure and mechanical behavior of the so-called spider silk gut fibers can be tailored to concur with those observed in naturally spun spider silk, except for effects related with the much larger cross-sectional area of the former. In particular spider silk gut has a proper ground state to which the material can revert independently from its previous loading history by supercontraction. A larger cross-sectional area implies that spider silk gut outperforms the natural material in terms of the loads that the fiber can sustain. This property suggests that it could substitute conventional spider silk fibers in some intended uses, such as sutures and scaffolds in tissue engineering.Ministerio de Economía y Competitividad (España) MAT2012-38412-C02-01Fondo Nacional de Ciencias Naturales de China 31160420, 31060282, 30760041Programa de Formación de Jóvenes Científicos (JingGang Star) 20133BCB2302