Liver-directed lentiviral gene therapy in a dog model of hemophilia B

We investigated the efficacy of liver-directed gene therapy using lentiviral vectors in a large animal model of hemophilia B and evaluated the risk of insertional mutagenesis in tumor-prone mouse models. We showed that gene therapy using lentiviral vectors targeting the expression of a canine factor IX transgene in hepatocytes was well tolerated and provided a stable long-term production of coagulation factor IX in dogs with hemophilia B. By exploiting three different mouse models designed to amplify the consequences of insertional mutagenesis, we showed that no genotoxicity was detected with these lentiviral vectors. Our findings suggest that lentiviral vectors may be an attractive candidate for gene therapy targeted to the liver and may be potentially useful for the treatment of hemophilia.

Razonamiento en geometría

Este artículo presenta algunas reflexiones adelantadas en el trabajo de investigación "Desarrollo del razonamiento a través de la geometría euclidiana" que llevamos a cabo en la actualidad. Se centra en dar una visión sobre el razonamiento en la actividad geométrica, los tipos de razonamiento que hemos identificado y una caracterización particular del razonamiento visual. Las ideas se ilustran por medio de relatos de situaciones vivenciadas con nuestros estudiantes de primer semestre, en cursos de geometría euclidiana, de la Universidad Pedagógica Nacional.

El infinito escolar

El presente trabajo forma parte de una investigación en la línea de la construcción social del conocimiento. El tema central de este reporte es la construcción escolar del infinito y las dificultades que éste concepto presenta debido a su origen sociocultural por un lado y matemático por otro. Se produce entonces un choque entre esos dos infinitos: el construido socialmente y desconocido por la escuela, y el matemático, que se utiliza en la escuela, pero es desconocido por los alumnos. Para indagar sobre la naturaleza del infinito con que se trabaja en el aula, se presenta y analiza una actividad, centrada en el estudio de funciones, y en particular de la existencia y cálculo de asíntotas que fue llevada a cabo con alumnos de escuela media. Las respuestas demuestran que el infinito construido fuera de la escuela sigue marcando en ellos la forma en que el infinito funciona y que el infinito matemático les presenta sólo conflictos y dudas.

Predicting the reliability of power electronic modules

This paper discusses the reliability of an IGBT power electronics module. This work is part of a major UK funded initiative into the design, packaging and reliability of power electronic modules. The predictive methodology combines numerical modeling techniques with experimentation and accelerated testing to identify failure modes and mechanisms for these type of power electronic module structures. The paper details results for solder joint failure substrate solder. Finite element method modeling techniques have been used to predict the stress and strain distribution within the module structures. Together with accelerated life testing, these results have provided a failure model for these joints which has been used to predict reliability of a rail traction application

A systematic methodology to assess the impact of human factors in ship design

Evaluating ship layout for human factors (HF) issues using simulation software such as maritimeEXODUS can be a long and complex process. The analysis requires the identification of relevant evaluation scenarios; encompassing evacuation and normal operations; the development of appropriate measures which can be used to gauge the performance of crew and vessel and finally; the interpretation of considerable simulation data. Currently, the only agreed guidelines for evaluating HFs performance of ship design relate to evacuation and so conclusions drawn concerning the overall suitability of a ship design by one naval architect can be quite different from those of another. The complexity of the task grows as the size and complexity of the vessel increases and as the number and type of evaluation scenarios considered increases. Equally, it can be extremely difficult for fleet operators to set HFs design objectives for new vessel concepts. The challenge for naval architects is to develop a procedure that allows both accurate and rapid assessment of HFs issues associated with vessel layout and crew operating procedures. In this paper we present a systematic and transparent methodology for assessing the HF performance of ship design which is both discriminating and diagnostic. The methodology is demonstrated using two variants of a hypothetical naval ship.

Biodiversity Loss in the Ocean: How Bad Is It?

MURAWSKI AND COLLEAGUES STATE THAT OUR assessment of the impacts of global marine biodiversity loss is overly pessimistic. They imply that management interventions are likely to reverse current trends of overfishing, and that the U.S. National Marine Fisheries Service (NMFS) has already met that goal. They cite Georges Bank haddock as an example and contest that catch metrics (as used in our global analysis) are sufficient to track the status of this particular fish stock and possibly others. We agree that precise biomass data are preferable, but these are rarely available. Here, we illustrate that catches are a good proxy of the status of haddock, although there can be a short delay in detecting recovery under intense management. While NMFS’s own data show that full recovery is still uncommon (<5% of overfished stocks) (1), we strongly agree that destructive trends can be turned around and that rebuilding efforts need to be intensified to meet that goal. But we must not miss the forest for the trees: Continuing focus on single, well-assessed, economically viable species will leave most of the ocean’s declining biodiversity under the radar.