Comparació dels sistemes "ribosome skipping" i "splicing acceptor" per a l'expressió de transgenes en adenovirus oncolítics

Report for the scientific sojourn carried out at the University of St. Andrews, United Kingdom, from November 2007 until January 2008. Therapeutic transgene expression is a valuable strategy to counteract the limitations associated with oncolytic adenoviruses. Late phase expression is desirable to avoid early cell death for proper virus production. In this 3 months-collaboration, we have constructed a late expression system based on ribosome skipping downstream fiber protein and compared it with a splicing-based method of late gene expression. Despite expressing high amounts of the transgene when utilizing the ribosome skipping-system, flow cytomety assays indicate a delayed transgene-expression kinetics compared with the splicing-based one. Furthermore, when using the ribosome skipping system not only fiber protein expression is more altered but also viral production. These results suggest splicing-based expression strategy as a more suitable system for expression of transgenes late in the viral life cycle of an oncolytic adenovirus.

Seguimiento a 5 años de pacientes con hepatits crónica C y respuesta viral sostenida

L'objectiu va ser avaluar la persistència de resposta viral sostinguda als 5 anys de seguiment en pacients amb hepatitis crònica per virus C tractats amb interferó pegilat i ribavirina. Des d'agost de 2001 fins a maig de 2004, es van incloure tots els pacients del nostre centre tractats amb interferó pegilat i ribavirina que van assolir resposta viral sostinguda. Es van recollir dades demogràfiques, histològiques, bioquímics i virològiques durant el tractament i als 5 anys d'haver obtingut la resposta viral sostinguda. Només un dels pacients va presentar recurrència virològica (taxa de recurrència viral a llarg termini molt baixa).

TFC : disseny d'aplicacions per a iOS Viral Zombies TD

Joc d'estrategia per a iPhone desenvolupat amb xCode.

A continuous strain-space model of viral evolution within a host

Viruses rapidly evolve, and HIV in particular is known to be one of the fastest evolving human viruses. It is now commonly accepted that viral evolution is the cause of the intriguing dynamics exhibited during HIV infections and the ultimate success of the virus in its struggle with the immune system. To study viral evolution, we use a simple mathematical model of the within-host dynamics of HIV which incorporates random mutations. In this model, we assume a continuous distribution of viral strains in a one-dimensional phenotype space where random mutations are modelled by di ffusion. Numerical simulations show that random mutations combined with competition result in evolution towards higher Darwinian fitness: a stable traveling wave of evolution, moving towards higher levels of fi tness, is formed in the phenoty space.

Simulation methods with extended stability for stiff biochemical kinetics

Background: With increasing computer power, simulating the dynamics of complex systems in chemistry and biology is becoming increasingly routine. The modelling of individual reactions in (bio)chemical systems involves a large number of random events that can be simulated by the stochastic simulation algorithm (SSA). The key quantity is the step size, or waiting time, τ, whose value inversely depends on the size of the propensities of the different channel reactions and which needs to be re-evaluated after every firing event. Such a discrete event simulation may be extremely expensive, in particular for stiff systems where τ can be very short due to the fast kinetics of some of the channel reactions. Several alternative methods have been put forward to increase the integration step size. The so-called τ-leap approach takes a larger step size by allowing all the reactions to fire, from a Poisson or Binomial distribution, within that step. Although the expected value for the different species in the reactive system is maintained with respect to more precise methods, the variance at steady state can suffer from large errors as τ grows. Results: In this paper we extend Poisson τ-leap methods to a general class of Runge-Kutta (RK) τ-leap methods. We show that with the proper selection of the coefficients, the variance of the extended τ-leap can be well-behaved, leading to significantly larger step sizes.Conclusions: The benefit of adapting the extended method to the use of RK frameworks is clear in terms of speed of calculation, as the number of evaluations of the Poisson distribution is still one set per time step, as in the original τ-leap method. The approach paves the way to explore new multiscale methods to simulate (bio)chemical systems.

Proyecto Kimbi : Márketing viral. Pásalo o no

“Un reciente estudio de la consultora Nielsen estima en 49.650 millones de € las pérdidas anuales procedentes de la inversión en publicidad no efectiva en el mundo”.Esta noticia refleja un hecho que causa alarmismo en la sociedad. Semejante gasto desbaratado en llevar a cabo un proyecto que no causa ningún beneficio es motivo de preocupación entre economistas y profesionales del Marketing. Ciertamente, entenderíamos que multitud de personas se llevasen las manos a la cabeza ante la evidencia de semejante despilfarro. Llegados a este punto, hay que comunicar dos hechos. En primer lugar, hemos de aclarar que este es un titular ficticio y los datos que se aportan son irreales.Lamentablemente, en segundo lugar se ha de exponer que las cifras estimadas reales duplican –siendo optimistas‐ las anteriormente citadas (1 “Advertising expenditure forecast 2008” ZenithOptimedia – Nielsen Facts 2008).Actualmente los expertos en Marketing están en medio de un proceso de búsqueda de nuevas fórmulas que aumenten la eficacia y reduzcan el gasto de sus campañas publicitarias, y ése es el terreno en donde se mueve el Marketing viral, fenómeno en plena expansión gracias a la creciente importancia de Internet en nuestras vidas.Este hecho fue lo que nos ha empujado a investigar sobre la disciplina y sus métodos.Descubrir qué se ocultaba detrás de la categoría “viral” y darnos cuenta de su imparable desarrollo, descubriendo cómo habíamos sido a la vez verdugos y mártires en la propagación de mensajes publicitarios.En nuestro trabajo queremos darle un nuevo sentido al concepto de ahorro en el Marketing viral, intentado descubrir si es posible llevar a cabo una transformación low‐cost del concepto de Marketing viral y aplicarla con éxito a un sector de lapoblación en el que podamos controlar los efectos de una campaña de dichas características, por lo cual escogimos a los estudiantes del campus de Ciutadella de la Universidad Pompeu Fabra como target de nuestra campaña.Además, nos planteamos analizar el ahorro de nuestra campaña mediante el análisis y comparación coste‐resultado de otras vías de Marketing tradicionales con un concepto novedoso y a la vez preciso como es el de “eficacia real publicitaria”, en el cual nos servimos de estudios sociopsicológicos de consumidores para establecer unosbaremos más cercanos a la realidad que los métodos más comunes de medición de resultados publicitarios.Para ello, es necesario crear una identidad completamente nueva. Es aquí donde surge la marca, franquicia, empresa, organización y filosofía –ficticias‐ Kimbi. Y el reto exige un esfuerzo notable: dar a conocer una identidad –comercial y empresarial‐ ficticia que no ofrece ningún servicio ni producto a un sector poblacional y crear expectativas en elobjetivo, llamar su atención, grabar en sus mentes nuestros identificativos y esperar que el virus del “movimiento Kimbi” se propague entre ellos con éxito. Es decir, competir en el saturado panorama publicitario contra multitud de multinacionales que ya tienen unos usuarios fieles y una reputación labrada, que ofrecen productos y servicios de manera gratuita en bastantes ocasiones y que disponen de ingentes cantidades de recursos y capital para publicitar su identidad comercial en multitud de medios mainstream con el objetivo de atraerles y causarles un impacto publicitario. Esperamos haber conseguido, al menos, que el lector sienta el deseo de ver el trabajo. ¿Queréis descubrir el resultado?

Fine-Tuning Translation Kinetics Selection as the Driving Force of Codon Usage Bias in the Hepatitis A Virus Capsid

Hepatitis A virus (HAV), the prototype of genus Hepatovirus, has several unique biological characteristics that distinguish it from other members of the Picornaviridae family. Among these, the need for an intact eIF4G factor for the initiation of translation results in an inability to shut down host protein synthesis by a mechanism similar to that of other picornaviruses. Consequently, HAV must inefficiently compete for the cellular translational machinery and this may explain its poor growth in cell culture. In this context of virus/cell competition, HAV has strategically adopted a naturally highly deoptimized codon usage with respect to that of its cellular host. With the aim to optimize its codon usage the virus was adapted to propagate in cells with impaired protein synthesis, in order to make tRNA pools more available for the virus. A significant loss of fitness was the immediate response to the adaptation process that was, however, later on recovered and more associated to a re-deoptimization rather than to an optimization of the codon usage specifically in the capsid coding region. These results exclude translation selection and instead suggest fine-tuning translation kinetics selection as the underlying mechanism of the codon usage bias in this specific genome region. Additionally, the results provide clear evidence of the Red Queen dynamics of evolution since the virus has very much evolved to re-adapt its codon usage to the environmental cellular changing conditions in order to recover the original fitness.

Comment on "Kinetics of spinodal decomposition in the ising model with vacancy diffusion"

In a recent paper [Phys. Rev. B 50, 3477 (1994)], P. Fratzl and O. Penrose present the results of the Monte Carlo simulation of the spinodal decomposition problem (phase separation) using the vacancy dynamics mechanism. They observe that the t1/3 growth regime is reached faster than when using the standard Kawasaki dynamics. In this Comment we provide a simple explanation for the phenomenon based on the role of interface diffusion, which they claim is irrelevant for the observed behavior.

Kinetics of martensitic transitions in Cu-Al-Mn under thermal cycling: Analysis at multiple length scales

In this paper we study the evolution of the kinetic features of the martensitic transition in a Cu-Al-Mn single crystal under thermal cycling. The use of several experimental techniques including optical microscopy, calorimetry, and acoustic emission, has enabled us to perform an analysis at multiple scales. In particular, we have focused on the analysis of avalanche events (associated with the nucleation and growth of martensitic domains), which occur during the transition. There are significant differences between the kinetics at large and small length scales. On the one hand, at small length scales, small avalanche events tend to sum to give new larger events in subsequent loops. On the other hand, at large length scales the large domains tend to split into smaller ones on thermal cycling. We suggest that such different behavior is the necessary ingredient that leads the system to the final critical state corresponding to a power-law distribution of avalanches.

Accuracy in the experimental calorimetric study of the crystallization kinetics and predicitve transformation diagrams: Application to a Ga-Te amorphous alloy

The uncertainties inherent to experimental differential scanning calorimetric data are evaluated. A new procedure is developed to perform the kinetic analysis of continuous heating calorimetric data when the heat capacity of the sample changes during the crystallization. The accuracy of isothermal calorimetric data is analyzed in terms of the peak-to-peak noise of the calorimetric signal and base line drift typical of differential scanning calorimetry equipment. Their influence in the evaluation of the kinetic parameters is discussed. An empirical construction of the time-temperature and temperature heating rate transformation diagrams, grounded on the kinetic parameters, is presented. The method is applied to the kinetic study of the primary crystallization of Te in an amorphous alloy of nominal composition Ga20Te80, obtained by rapid solidification.