Development of stealth transgenes for gene therapy : evaluation of cis-acting inhibitors of antigen presentation

In gene therapy, expression of a corrected gene leads to synthesis of proteins foreign to the immune system. Cells expressing these will therefore be recognized as aberrant and destructed. We used a known immune evasion mechanism to "stealth" transgene products. We fused the coding sequence of the Gly-Ala repeats (GAr) of the Epstein-Barr Virus (EBV) nuclear antigen 1 (EBNA-1) with three different transgenes, i.e. E.coli LacZ, firefly Luciferase and herpes simplex virus 1 thymidine kinase (TK). We show that the EBV GAr system could well be used to prevent the immune system of reacting on transgenes. We could also show, that GAr-TK might be a good candidate to use in bone marrow transplantation protocols. In addition to the GAr, we used an alternative open reading frame found within the ENBA-1 sequence (GZr). We made a fusion of the GZr with the LacZ gene and show that, in contrast to a repeat deleted construct, the construct bearing repeats was protected for recognition by LacZ specific CTLs. This shows that the GZ repeats might be another candidate to shield transgenes for the immune system. The human herpes virus 8 (HHV-8) has a protein like EBNA-1, involved in establishing latency, latency-associated nuclear antigen-1 (LANA-1). We show that LANA-1, like EBNA-1, possesses an immune evasion effect.LEI Universiteit LeidenMoleculaire Virologie en Gentherapi

DAVINC3I: moving towards responsive hub network designs

The Dutch floricultural sector is generally appreciated for its world leadership; the Netherlands is the flower trading hub for the European market. There are two trends affecting this position. First, virtualisation makes trade flows relatively footloose and flexible. Moreover, it enables the use of better and more information in logistics decision making. Second, internationalisation of markets and production has increased the size of the global market and associated distances. To maintain leadership, the Dutch floricultural sector has initiated the Dinalog DaVinc3i project. In this paper we outline the activities we are currently undertaking and some of the outcomes achieved so far. This includes the effects of orchestration in floriculture logistics and the development of a new logistics network model for floriculture logistics. Subsequently we will provide a brief overview of some of the student projects carried out within the DaVinc3i project: reasons for outsourcing floriculture logistics in export flows, pooling of inventory by florists and collection of flowers in a small network. Finally, aspects of collaboration for product quality are addressed, as well as recommendations for a cooperative business model for a B2C web shop for plants and flowers

Coupled transcriptome and proteome analysis of human lymphotropic tumor viruses: insights on the detection and discovery of viral genes

<p>Abstract</p> <p>Background</p> <p>Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are related human tumor viruses that cause primary effusion lymphomas (PEL) and Burkitt's lymphomas (BL), respectively. Viral genes expressed in naturally-infected cancer cells contribute to disease pathogenesis; knowing which viral genes are expressed is critical in understanding how these viruses cause cancer. To evaluate the expression of viral genes, we used high-resolution separation and mass spectrometry coupled with custom tiling arrays to align the viral proteomes and transcriptomes of three PEL and two BL cell lines under latent and lytic culture conditions.</p> <p>Results</p> <p>The majority of viral genes were efficiently detected at the transcript and/or protein level on manipulating the viral life cycle. Overall the correlation of expressed viral proteins and transcripts was highly complementary in both validating and providing orthogonal data with latent/lytic viral gene expression. Our approach also identified novel viral genes in both KSHV and EBV, and extends viral genome annotation. Several previously uncharacterized genes were validated at both transcript and protein levels.</p> <p>Conclusions</p> <p>This systems biology approach coupling proteome and transcriptome measurements provides a comprehensive view of viral gene expression that could not have been attained using each methodology independently. Detection of viral proteins in combination with viral transcripts is a potentially powerful method for establishing virus-disease relationships.</p

The influence of student characteristics on the use of adaptive e-learning material

Adaptive e-learning materials can help teachers to educate heterogeneous student groups. This study provides empirical data about the way academic students differ in their learning when using adaptive e-learning materials. Ninety-four students participated in the study. We determined characteristics in a heterogeneous student group by collecting demographic data and measuring motivation and prior knowledge. We also measured the learning paths students followed and learning strategies they used when working with adaptive e-learning material in a molecular biology course. We then combined these data to study if and how student characteristics relate to the learning paths and strategies they used. We observed that students did follow different learning paths. Gender did not have an effect, but (mainly Dutch) BSc students differed from (international) MSc students in the intrinsic motivation they had and the learning paths and strategies they followed when using the adaptive e-learning material. (C) 2011 Elsevier Ltd. All rights reserved

DAVINC3I: moving towards responsive hub network designs

The Dutch floricultural sector is generally appreciated for its world leadership; the Netherlands is the flower trading hub for the European market. There are two trends affecting this position. First, virtualisation makes trade flows relatively footloose and flexible. Moreover, it enables the use of better and more information in logistics decision making. Second, internationalisation of markets and production has increased the size of the global market and associated distances. To maintain leadership, the Dutch floricultural sector has initiated the Dinalog DaVinc3i project. In this paper we outline the activities we are currently undertaking and some of the outcomes achieved so far. This includes the effects of orchestration in floriculture logistics and the development of a new logistics network model for floriculture logistics. Subsequently we will provide a brief overview of some of the student projects carried out within the DaVinc3i project: reasons for outsourcing floriculture logistics in export flows, pooling of inventory by florists and collection of flowers in a small network. Finally, aspects of collaboration for product quality are addressed, as well as recommendations for a cooperative business model for a B2C web shop for plants and flowers