Neuronal circuitry reconstruction after stem cell therapy in damaged brain

[No abstract

Loss of HIF-1α accelerates murine FLT-3ITD-induced myeloproliferative neoplasia.

Hypoxia-induced signaling is important for normal and malignant hematopoiesis. The transcription factor hypoxia-inducible factor-1α (HIF-1α) plays a crucial role in quiescence and self-renewal of hematopoietic stem cells (HSCs) as well as leukemia-initiating cells (LICs) of acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). We have investigated the effect of HIF-1α loss on the phenotype and biology of FLT-3(ITD)-induced myeloproliferative neoplasm (MPN). Using transgenic mouse models, we show that deletion of HIF-1α leads to an enhanced MPN phenotype reflected by higher numbers of white blood cells, more severe splenomegaly and decreased survival. The proliferative effect of HIF-1α loss is cell-intrinsic as shown by transplantation into recipient mice. HSCs loss and organ specific changes in number and percentage of long-term hematopoietic stem cells (LT-HSCs) were the most pronounced effects on a cellular level after HIF-1α deletion. Furthermore, we found a metabolic hyperactivation of malignant cells in the spleen upon loss of HIF-1α. Some of our findings are in contrary to what has been previously described for the role of HIF-1α in other myeloid hematologic malignancies and question the potential of HIF-1α as a therapeutic target.Leukemia accepted article preview online, 24 June 2015. doi:10.1038/leu.2015.156

Numerical evaluation of the Green's functions for arbitrarily shaped cylindrical enclosures and their optimization by a new spatial images method

IIn this paper, a spatial image technique is used to efficiently calculate the mixed potential Green’s functions associated with electric sources, when they are placed inside arbitrarily shaped cylindrical cavities. The technique is based on placing electric dipole images and charges outside the cavity region. Their strength and orientation are thencalculated by imposing the appropriate boundary conditions for the fields at discrete points on the metallic wall. A method for the assessment of the potentials accuracy is proposed, and several optimization techniques are presented. Three cavities are analyzed to demonstrate the usefulness of the techniques. The cutoff frequencies and potentials patterns are compared to those obtained by a standard finite elements technique, showing excellent agreement. Finally, a band-pass filter based on coupled lines is analyzed, demonstrating the practical value of the technique.This work has been developed with support from the Spanish National Project (CICYT) with reference TEC2004-04313-C02-02/TCM, and the Regional Seneca Project with reference 02972/PI/0

Application of the high-gain substrate-superstrate configuration to dielectric leaky-wave antennas

The high-gain substrate-superstrate configuration, which was proposed to increase the gain in printed circuit antennas, is applied to dielectric leaky-wave antennas (LWAs) to improve its frequency response. Analysis of a slitted suspended dielectric rectangular waveguide is carried out using a full-wave method. It is proved that the minimum values of the leakage constant of the leaky-wave mode for the suspended configuration are related to the high-gain resonance conditions. Moreover, it is found that the suspended LWA exhibits very small beamwidth variations in a large frequency bandwidth. It is well-known that inhomogeneous filled LWAs suffer from variation of beamwidth as the angle of maximum radiation is scanned with frequency. The proposed topology can be adjusted so that a flat response of the beamwidth can be obtained in a large frequency band, while maintaining the frequency-scanning behavior of the LWA.This work was supported by Spanish National Projects ESP2001-4546-PE and TIC2000-0591- C03-03, by Regional Seneca Projects 2002 PB/4/FS/02 and PMPDI-UPCT- 2004, and by the EPSON-Ibérica Foundation

Analysis and design of periodic leaky-wave antennas for the millimeter waveband in hybrid waveguide-planar technology

This work presents a full-wave integral equation approach specifically conceived for the analysis and design of laterally-shielded rectangular dielectric waveguides, periodically loaded with planar perturbations of rectangular shape. This type of open periodic waveguide supports the propagation of leaky-wave modes, which can be used to build leaky-wave antennas which exhibit many desirable features for millimeter waveband applications. The particularities of the leaky-mode analysis theory are described in this paper, and comparisons with other methods are presented for validation purposes. Using this leaky-mode analysis method, a novel periodic leaky-wave antenna is presented and designed. This novel antenna shows some important improvements with respect to the features of previously proposed antennas. The results of the designed radiation patterns are validated with three-dimensional electromagnetic analysis using commercial software.This work was supported by Spanish National projects ESP2001-4546-PE and TEC2004-04313-C02-02/TCM and Regional Séneca projects 2002 PB/4/FS/02. The authors would like to thank the EPSON-Ibérica Foundation for its stimulating support. and PMPDI-UPCT-2004. The authors would like to thank the EPSON-Ibérica Foundation for its stimulating support

Novel microwave network for the leaky-wave analysis of evanescent fields in stub-loaded structures

In this paper, a new transverse equivalent network for the modal analysis of stub-loaded leaky-wave antennas is developed. The derived network is useful for the study of the radiation of evanescent fields that occurs when they reach the top aperture of the parallel-plate stub. This transverse network is based, for the first time, on a nonhybrid formulation of the constituent parallel- plates modes of order 1 (TE 1 andTM 1 ). The obtained network is an alternative to the one based on hybrid TE 1 andTM 1 modes, and leads to a simpler transverse resonance equation. The new equivalent network is validated by obtaining leaky-mode dispersion curves for a previously studied leaky-wave antenna in nonradiative dielectric guide technology.This work was supported under the Spanish National Project TEC2004-04313-C02-02/ TCM, under the Regional Seneca Project 02972/PI/05, and under Regional Scholarship PMPDI-UPCT-2007

Proyecto ARIAM: desarrollo de un radiotelescópio y de un taller de Radioastronomía e Ingeniería de alta frecuencia como herramienta para el fomento de la cultura científica y tecnológica en la UPCT

En esta comunicación pretendemos dar a conocer una iniciativa de fomento de la cultura científica y tecnológica dentro del área de Radioastronomía e Ingeniería de Telecomunicaciones, que se ha denominado proyecto ARIAM (Aula-taller de Radioastronomía e Ingeniería de Antenas y circuitos de Microondas). Esta iniciativa tiene como punto de inicio el desarrollo de un Radiotelescopio de microondas por parte de los alumnos de último cursos de la Escuela Técnica Superior de Ingeniería de Telecomunicación (ETSIT) de la Universidad Politécnica de Cartagena (UPCT). El Radiotelescopio consta, básicamente, de una antena parabólica de unos 3 metros de diámetro, de un receptor de microondas de elevada sensibilidad y ganancia, y de un sistema de adquisición de datos y control del apuntamiento de la antena. Se trata de un proyecto de ingeniería complejo y de un reto tecnológico, que involucra el desarrollo de varios subproyectos de naturaleza multidisciplinar. Están implicadas áreas temáticas como la ingeniería de antenas, la ingeniería de circuitos de microondas, la instrumentación electrónica, la ingeniería mecánica, técnicas de adquisición y procesado digital de la señal, la ingeniería de control y de motores, la astrofísica… etc. La novedad y el interés docente estriban en que todos estos subproyectos están siendo dirigidos por profesores de la UPCT, y son desarrollados íntegramente por alumnos de esta misma Universidad, utilizando los conocimientos y los laboratorios disponibles en las instalaciones de la UPCT. Es la primera vez en España que un sistema tan complejo y tecnológicamente avanzado como un Radiotelescopio está siendo desarrollado íntegramente con recursos humanos y tecnológicos de una Universidad Pública. Un objetivo fundamental de esta iniciativa es el de trasladar a la sociedad murciana en general, y a los más jóvenes en particular, un mensaje claro y vital en estos momentos: nuestros actuales y futuros estudiantes universitarios tienen a su disposición los medios para adquirir los conocimientos y habilidades necesarias que permiten abordar proyectos tan interesantes como los que se describirán en la ponencia. En esta misma ponencia se resumirá el trabajo realizado hasta la fecha durante los cuatro años que lleva en marcha esta actividad. Se mostrarán los resultados obtenidos, tanto a nivel técnico como a nivel humano, haciendo hincapié en la respuesta que han dado los alumnos a esta propuesta y las habilidades que ellos mismos están desarrollando gracias a este proyecto. Cabe destacar el trabajo en equipo, el carácter multidisciplinar del mismo, el desarrollo de habilidades prácticas y competencias profesionales como el manejo de maquinaria de fabricación de circuitos y estructuras, o de instrumentación de testeo y ajuste de circuitos… etc. El Radiotelescopio será usado para difundir entre alumnos, profesores y público en general la tecnología que hace posible la concepción y puesta en marcha del mismo, así como la disciplina de la Radioastronomía, tan interesante como desconocida. Con este objetivo de difusión, todos los sistemas que están siendo desarrollados tienen una finalidad claramente divulgativa, buscando siempre la claridad de los conceptos que se pretenden transmitir. Asimismo, en la ponencia se describirán las posibilidades de ampliación y mejora del Radiotelescopio, de manera que se entienda por qué este proyecto está pensado para ser más que un mero instrumento de observación, parte de un aula-taller de aprendizaje y difusión de la tecnología de antenas y circuitos de alta frecuencia. Por supuesto, este Radiotelescopio además de para divulgación será usado para tareas científicas de observación del Universo, y en concreto para detectar las señales de microondas originadas por el hidrógeno atómico presente en las nebulosas que pueblan nuestra Galaxia. Además de ser un instrumento para astrofísicos y radioastrónomos profesionales, el Radiotelescopio estará a disposición de las asociaciones astronómicas amateurs regionales, como la Agrupación Astronómica de la Región de Murcia (AARM) o la Asociación Astronómica de Cartagena (AAC). Además, el Radiotelescopio formará parte del proyecto internacional SETI (Search of Extraterrestrial Intelligence), cuya misión es buscar posibles señales de radio extraterrestres que tengan un origen artificial. En la ponencia se mostrarán las bondades de este proyecto ARIAM para fomentar el interés por las carreras de Ciencia e Ingeniería en nuestra Región. Además, este proyecto cuenta con el apoyo de varias universidades del territorio nacional y del Instituto Astrofísico de Canarias, adquiriendo un carácter interterritorial. El desarrollo del Radiotelescopio de ARIAM ha sido financiado por la Fundación regional Séneca durante los años 2006, 2007 y 2008.El desarrollo de este Radiotelescopio no habría sido posible sin la financiación ofrecida durante los años 2006, 2007 y 2008 por la Fundación Regional Séneca [37]. De igual o mayor valor es la ilusión mostrada por todos los alumnos de la ETSIT de la UPCT que han colaborado o están colaborando en el proyecto ARIAM, los cuales nombramos por orden cronológico: Ricardo Alarcón Llamas (LNAs v1.0, curso 2005-2006), Pedro Enrique Ros Avilés (mixer v1.0, curso 2005-2006), Anna Kamasheva (LNA v2.0, curso 2006-2007), Gonzalo Peñafiel Beltrán (LNA v3.0, curso 2006-2007), Mónica Moragón Serano (oscilador, curso 2006-2007), Adrián Juan Heredia (bocina, curso 2006-2007), Francisco J. Sandoval Piqueras (mixer v2.0, curso 2006-2007), Javier Molero Madrid (sistema, curso 2007-2008), Jesús Mora Rodríguez (sistema, curso 2007-2008) y Marta Rodríguez García Rodríguez (sistema, curso 2007-2008). Asimismo, la dedicación de los profesores Fernando Quesada Pereira, Alejandro Álvarez Melcón, Jose María Molina García-Pardo, David Cañete Rebenaque y José Luis Gómez Tornero, de la ETSIT de la UPCT, ha sido vital para conseguir llegar hasta el punto en el que está el proyecto ARIAM

Poly(ester amide) microspheres are efficient vehicles for long-term intracerebral growth factor delivery and improve functional recovery after stroke

Growth factors promote plasticity in injured brain and improve impaired functions. For clinical application, efficient approaches for growth factor delivery into the brain are necessary. Poly(ester amide) (PEA)-derived microspheres (MS) could serve as vehicles due to their thermal and mechanical properties, biocompatibility and biodegradability. Vascular endothelial growth factor (VEGF) exerts both vascular and neuronal actions, making it suitable to stimulate post-stroke recovery. Here, PEA (composed of adipic acid, L-phenyl-alanine and 1,4-butanediol) MS were loaded with VEGF and injected intracerebrally in mice subjected to cortical stroke. Loaded MS provided sustained release of VEGF in vitro and, after injection, biologically active VEGF was released long-term, as evidenced by high VEGF immunoreactivity, increased VEGF tissue levels, and higher vessel density and more NG2+ cells in injured hemisphere of animals with VEGF-loaded as compared to non-loaded MS. Loaded MS gave rise to more rapid recovery of neurological score. Both loaded and non-loaded MS induced improvement in neurological score and adhesive removal test, probably due to anti-inflammatory action. In summary, grafted PEA MS can act as efficient vehicles, with anti-inflammatory action, for long-term delivery of growth factors into injured brain. Our data suggest PEA MS as a new tool for neurorestorative approaches with therapeutic potential

Long-term calcium imaging reveals functional development in hiPSC-derived cultures comparable to human but not rat primary cultures

Models for human brain-oriented research are often established on primary cultures from rodents, which fails to recapitulate cellular specificity and molecular cues of the human brain. Here we investigated whether neuronal cultures derived from human induced pluripotent stem cells (hiPSCs) feature key advantages compared with rodent primary cultures. Using calcium fluorescence imaging, we tracked spontaneous neuronal activity in hiPSC-derived, human, and rat primary cultures and compared their dynamic and functional behavior as they matured.We observed that hiPSC-derived cultures progressively changed upon development, exhibiting gradually richer activity patterns and functional traits. By contrast, rat primary cultures were locked in the same dynamic state since activity onset. Human primary cultures exhibited features in between hiPSC-derived and rat primary cultures, although traits from the former predominated. Our study demonstrates that hiPSC-derived cultures are excellent models to investigate development in neuronal assemblies, a hallmark for applications that monitor alterations caused by damage or neurodegeneration

Analysis of Thick Wire Antennas Using a Novel and Simple Kernel Treatment

This paper presents novel aspects concerning the analysis of thick-wire antennas. The analysis is carried out using an integral equation (IE) technique, in which the kernel is treated with a novel numerical-integration procedure. A comparison with other techniques are included, showing the advantages of the newly proposed method. The novel treatment of the kernel requires the efficient extraction of the singularities. For this purpose, two different techniques are presented, and their advantages and drawbacks are discussed. Using the procedure proposed, complex thick wire antennas with rotational symmetry are analyzed. A combined antenna composed of cylindrical and conical sections is studied. The results show that the new techniques derived are efficient and lead to accurate results