High Throughput Screening for the Enhancement of Adeno-Associated Virus Type 2 Transduction

Adeno-associated virus (AAV) is a promising vector for human gene therapy. Although more effective than non-viral vectors, AAV still requires improvement in efficacy in order to become a successful gene therapy vector. With this in mind, we have sought to identify and examine identified enhancers of adeno-associated virus type 2 (AAV2) transduction. Using a high throughput screening system with recombinant AAV2 carrying the luciferase reporter gene (AAV2-Luc), we found siRNA sequences and chemical compounds which increase AAV2 reporter gene expression. We specifically identified a hexamer seed region 5’-UGUUUC-3’ which facilitated AAV2 transduction. Chemical compound enhancers included ellagic acid, 1,10-phenanthroline, EGFR tyrosine kinase inhibitors, nucleoside analogs, and DNA alkylating agents. Although several of these compounds, such as EGFR tyrosine kinase inhibitors and DNA alkylating agents, were known enhancers of AAV transduction, compounds such as ellagic acid and 1,10-phenanthroline were newly identified as facilitating AAV2 transduction. After identifying these enhancers, we have further sought to understand a mechanistic basis for them through studies which individually quantified enhancement at stages including the virus-receptor interaction, the viral DNA introduction into the cell, reporter gene RNA transcription, and the production of protein from the transgene. The identification of siRNAs and chemical compounds which enhance transduction can lead to a better understanding of AAV2 biology and may provide a foundation for the engineering of novel AAV formulations, delivery systems, or vectors

De los afectos

The ongoing research with choreographer Juan Carlos Garcia and his company, Lanonima Imperial, is based Oil a continual dialogue about the body in space and its dialogue with electronic timebased media. In each iteration or new production we work to extend and advance this relational knowledge set building. Most productions arc shown between 10 and 20 venues across Europe, allowing for further refinement within the production cycle. Projects are extensively workshopped and previewed in small theatres before opening. Innovative ideas, new techniques and combinations of custom software solutions, interactive systems, robotics and new display technologies allow us to create new mediated spaces. Through the refinement and re-Interpretation of existing technologies and a reflective approach to an eleven year collaboration, we have made significant conceptual advances in the use of media on stage and the usc of the body as machine interface. In this work the research focused on the framing of nature through video and technical solutions regarding the kinetic movements of display systems, based on content and spatial location. 5 channels x 80 minutes video

La Mar de Formas

The ongoing research with choreographer Juan Carlos Garcia and his company Lanonima Imperial is based on a continual dialogue about the body in space and its dialogue with electronic time-based media. In each iteration or new production we work to extend and advance this relational knowledge set building. Most productions are shown between 10 and 20 venues across Europe allowing for further refinement within the production cycle. Projects are extensively workshopped and previewed in small theatres before opening. Innovative ideas, new techniques and combinations of custom software solutions, interactive systems, robotics and new display technologies allow us to create new mediated spaces. Through the refinement and re-interpretation of existing technologies and a reflective approach to an eleven-year collaboration, we have made significant conceptual advances in the use of media on stage and the use of the body as machine interface. "The pure forms of knowledge are science, art and revelation, or rather, beliefs. The scientific method is used to deal with ideas but not to have new ideas. That is why the scientist has to be aware of art, of its capacity for intuition." (Prof. Wagensberg) In collaboration with Jorge Wagensberg, Professor for Theory of Irreversible Processes (University of Barcelona), the work engaged in a dialogue between mediated representation, dance and scientific thought in order to both advance and give meaning to the production, but also to provoke new ideas about the science of forms

Novel Magnet Production Technique Used for an Elliptically Polarizing Undulator

A common problem for elliptically polarizing undulators EPUs is that the magnetic forces give a mechanical deflection in the magnet holder construction when changing the undulator phase. Gluing horizontally and vertically magnetized blocks together can increase the mechanical stability of the magnet holders. The gluing process of pairs of magnetized magnet blocks is time consuming, expensive and difficult to carry out with high positional precision. A novel magnet production technique has been developed where un magnetized pairs of blocks are glued together before magnetization. The large number of parts, the time for assembly, and the cost of the EPU can be reduced with the novel magnet production technique. The novel magnet production method has been used for a 2.6 m long EPU of APPLE II type, which has been built in house at the MAX IV Laboratory. The frame for the EPU is made of cast iron in order to get a small mechanical deformation when changing phase in the inclined mode. The paper includes detailed descriptions of the novel magnet production technique, including measurements of the magnetization, and the new EP

The Role of Zooxanthellae in Marine Invertebrates

The importance of zooxanthellae in marine environments cannot be understated. Their role as a source of nutritive energy to corals underpins the success of reef-building systems worldwide, forming some of the most productive ecosystems on earth. The diversity of these unicellular symbiotic algae, which belong to the genus Symbiodinium, is enormous. Multiple hosts, multiple types of algae and the diverse habitats in which these organisms are found suggests a diverse reservoir of symbiont types in almost every region. This review focuses on the functional and genetic diversity of Symbiodinium, the specificity and flexibility of the host-algal association, and the implications they present. Symbiodinium types vary in their physiological response to environmental changes, and the possibility that hosts may alter their populations of symbiotic algae in response to external change might suggest zooxanthellae influence the ecological resilience of host species. This then raises the question of whether or not these changes are sufficient for hosts to tolerate climate change and other negative impacts on aquatic ecosystems worldwide

Incisional Hernia in a 12-mm Nonbladed Trocar Site Following Laparoscopic Nephrectomy

Non-bladed trocars and radially dilating systems are considered less traumatic to the abdominal wall because they do not incise the fascia itself. Since the fascia is not cut, it has believed that the fascia closes by itself. Consequently, several authors have suggested that closure of the abdominal fascia may be unnecessary when such non-bladed laparoscopic trocars are used. We report of a case in which a port site hernia was diagnosed at the site of a 12 mm non-bladed trocar 11 days after laparoscopic nephrectomy. Although it may be true that in many cases port site closure is unnecessary and does not result in bowel herniation, this case along with a prior report serve as important reminders that port site hernias are possible even in the use of non-bladed or radial dilating systems, and that there exists a number of potential variables that may predispose to herniation and consequently the ability to predict such events in individual patients remains uncertain. As such, we recommend closing 10 mm or larger port sites irrespective of trocar design

Correspondence between geometrical and differential definitions of the sine and cosine functions and connection with kinematics

In classical physics, the familiar sine and cosine functions appear in two forms: (1) geometrical, in the treatment of vectors such as forces and velocities, and (2) differential, as solutions of oscillation and wave equations. These two forms correspond to two different definitions of trigonometric functions, one geometrical using right triangles and unit circles, and the other employing differential equations. Although the two definitions must be equivalent, this equivalence is not demonstrated in textbooks. In this manuscript, the equivalence between the geometrical and the differential definition is presented assuming no a priori knowledge of the properties of sine and cosine functions. We start with the usual length projections on the unit circle and use elementary geometry and elementary calculus to arrive to harmonic differential equations. This more general and abstract treatment not only reveals the equivalence of the two definitions but also provides an instructive perspective on circular and harmonic motion as studied in kinematics. This exercise can help develop an appreciation of abstract thinking in physics.Comment: 6 pages including 1 figur