Modular magnetite-filled nanomicelles for multimodal imaging-guided development of effective anticancer vaccines

188 p.Tanto las células cancerosas como muchos de los patógenos que causan enfermedades crónicas han desarrollado mecanismos para evadir al sistema inmune. Por lo tanto, es necesario desarrollar nuevas tecnologías que nos permitan conseguir vacunas novedosas, seguras y efectivas contra este tipo de enfermedades.En esta tesis se propone un sistema de trasporte capaz de dirigir antígenos tumorales y/o adyuvantes hasta los órganos secundarios linfoides (bazo y nódulos linfáticos) con el propósito de generar una respuesta inmune potente y específica contra el cáncer. Este tipo de sistema de transporte se basa en nanopartículas de óxido de hierro recubiertas con un polímero bio-compatible, lo cual permite conferir propiedades únicas a estas vacunas `sub-unitarias¿.Gracias al tamaño nanométrico, estas vacunas son capaces de transportar ambos tipos de moléculas inmunogénicas a las mismas poblaciones de células presentes en los nódulos linfáticos y, del mismo modo, permiten la interacción con receptores/compartimentos celulares específicos. Este transporte dirigido implica una mejora considerable de la eficacia de la inmunización, incluso a dosis bajas, permitiendo una respuesta inmune humoral y celular específica contra el tumor.Mediante el marcaje de estas nano-vacunas con un fluoróforo (rodamina B) y el radioisótopo 67Ga, es posible estudiar su interacción con las células, su comportamiento en medios fisiológicos y su biodistribución in vivo, mediante técnicas de imagen no-invasivas.Estas nano-vacunas han demostrado ser materiales muy prometedores para el desarrollo de nuevas vacunas contra el cáncer.CIC BiomaGUN

Monte Carlo simulations with few DOF’s in large molecules

This Technical Report introduces a data structure and an algorithm to efficiently to efficiently determine rigid clusters in a given molecule. This is a relevant problem in Monte Carlo simulations where the actuated DOFs change at each iteration. If the number of actuated DOFs is small, large temporary rigid groups appear during the time spanned by a MCS step. This document also provides a way of calculating the total energy in the molecules taking into account only inter-rigid energy terms. Thus, a large fraction of energy terms are not required to be computed, namely intra-rigid terms.Postprint (published version

The impact of government financial support on the performance of new firms : the role of competitive advantage as an intermediate outcome

This research examines the influence of government financial support on new firms' performance. Extant empirical research on the topic has found mixed results, which warrants an exploration of the theoretical basis for the impact of support policies on new firms' performance. Grounding the theoretical model in the resource-based view and institutional theories, this study contends that performance outcomes - e.g., revenues or profits - should not be the first outcomes of public policies to be examined. Instead, competitive advantage formation is suggested as a link between support policies and new firms' performance. Using new firms from the U.S., we examine the impact of government financial support measures - government loans, guarantees and government equity - on firms' overall competitive advantage and more specific types of competitive advantage based on innovation, licensing-in, marketing, and human capital. Controlling for family funding, bank financing, equity of business angels and venture capitalists, industry, size, as well as entrepreneur's characteristics, the results reveal that government guarantees and government equity have a direct effect on new firms' competitive advantage and only an indirect impact on performance. Our results suggest to policy makers to focus on helping new firms build the necessary capabilities to compete successfully in the marketplace

On-line learning with minimal degradation in feedforward networks

Dealing with non-stationary processes requires quick adaptation while at the same time avoiding catastrophic forgetting. A neural learning technique that satisfies these requirements, without sacrifying the benefits of distributed representations, is presented. It relies on a formalization of the problem as the minimization of the error over the previously learned input-output (i-o) patterns, subject to the constraint of perfect encoding of the new pattern. Then this constrained optimization problem is transformed into an unconstrained one with hidden-unit activations as variables. This new formulation naturally leads to an algorithm for solving the problem, which we call Learning with Minimal Degradation (LMD). Some experimental comparisons of the performance of LMD with back-propagation are provided which, besides showing the advantages of using LMD, reveal the dependence of forgetting on the learning rate in back-propagation. We also explain why overtraining affects forgetting and fault-tolerance, which are seen as related problems.Peer Reviewe

Statistical measure of complexity for quantum systems with continuous variables

The Fisher-Shannon statistical measure of complexity is analyzed for a continuous manifold of quantum observables. It is probed then than calculating it only in the configuration and momentum spaces will not give a complete description for certain systems. Then a more general measure for the complexity of a quantum system by the integration of the usual Fisher-Shannon measure over all the parameter space is proposed. Finally, these measures are applied to the concrete case of a free particle in a box.Comment: 6 pages, 5 figures. Published versio

Exploiting single-cycle symmetries in branch-and-prune algorithms

As a first attempt to exploit symmetries in continuous con- straint problems, we focus on permutations of the variables consisting of one single cycle. We propose a procedure that takes advantage of these symmetries by interacting with a Branch-and-Prune algorithm without interfering with it. A key concept in this procedure are the classes of symmetric boxes formed by bisecting a n-dimensional cube at the same point in all dimensions at the same time. We quantify these classes as a function of n. Moreover, we propose a simple algorithm to generate the representatives of all these classes for any number of variables at very high rates. A problem example from the chemical field and a kinematics solver are used to show the performance of the approach in practice.Peer Reviewe

Exploiting single-cycle symmetries in branch-and-prune algorithms

The final publication is available at link.springer.comAs a first attempt to exploit symmetries in continuous constraint problems, we focus on permutations of the variables consisting of one single cycle. We propose a procedure that takes advantage of these symmetries by interacting with a Branch-and-Prune algorithm without interfering with it. A key concept in this procedure are the classes of symmetric boxes formed by bisecting a n-dimensional cube at the same point in all dimensions at the same time. We quantify these classes as a function of n. Moreover, we propose a simple algorithm to generate the representatives of all these classes for any number of variables at very high rates. A problem example from the chemical field and a kinematics solver are used to show the performance of the approach in practice.Peer ReviewedPostprint (author's final draft

Solving the mystery of booming sand dunes

Desert booming can be heard after a natural slumping event or during a sand avalanche generated by humans sliding down the slip face of a large dune. The sound is remarkable because it is composed of one dominant audible frequency (70 to 105 Hz) plus several higher harmonics. This study challenges earlier reports that the dunes’ frequency is a function of average grain size by demonstrating through extensive field measurements that the booming frequency results from a natural waveguide associated with the dune. The booming frequency is fixed by the depth of the surficial layer of dry loose sand that is sandwiched between two regions of higher compressional body wave velocity. This letter presents measurements of the booming frequencies, compressional wave velocities, depth of surficial layer, along with an analytical prediction of the frequency based on constructive interference of propagating waves generated by avalanching along the dune surface

Reply to comment by B. Andreotti et al. on "Solving the mystery of booming sand dunes"

This reply addresses three main issues raised in the comment of Andreotti et al. [2008]. First, the turning of ray paths in a granular material does not preclude the propagation of body waves and the resonance condition described by Vriend et al. [2007]. The waveguide model still holds in the dune for the observed velocities, even with a velocity increase with depth as implied by Andreotti et al. [2008]. Secondly, the method of initiation of spontaneous avalanching does not influence the booming frequency. The frequency is independent of the source once sustained booming starts; it depends on the subsurface structure of the dune. Thirdly, if all data points from Vriend et al. [2007] are included in the analysis (and not an average or selection), no correlation is observed between the sustained booming frequency and average particle diameter

Sistematización de la experiencia docente en la asignatura cultura artística, para el fortalecimiento del pensamiento crítico de los estudiantes de primer semestre de la licenciatura en educación básica con énfasis en ciencias sociales de la Universidad Pedagógica Nacional

La presente investigación surge por la necesidad de sistematizar la experiencia docente de la asignatura Cultura Artística, que se ofrece dentro de la Licenciatura en Educación básica con énfasis en Ciencias Sociales de la Universidad Pedagógica Nacional UPN, en relación con los aportes que esta brinda en la construcción y formación de pensamiento crítico de los futuros profesores de historia y geografía