Science Requirements and Conceptual Design for a Polarized Medium Energy Electron-Ion Collider at Jefferson Lab

This report presents a brief summary of the science opportunities and program of a polarized medium energy electron-ion collider at Jefferson Lab and a comprehensive description of the conceptual design of such a collider based on the CEBAF electron accelerator facility.Comment: 160 pages, ~93 figures This work was supported by the U.S. Department of Energy, Office of Nuclear Physics, under Contract No. DE-AC05-06OR23177, DE-AC02-06CH11357, DE-AC05-060R23177, and DESC0005823. The U.S. Government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or reproduce this manuscript for U.S. Government purpose

Functional Diversity of Human Basic Helix-Loop-Helix Transcription Factor TCF4 Isoforms Generated by Alternative 5′ Exon Usage and Splicing

BACKGROUND: Transcription factor 4 (TCF4 alias ITF2, E2-2, ME2 or SEF2) is a ubiquitous class A basic helix-loop-helix protein that binds to E-box DNA sequences (CANNTG). While involved in the development and functioning of many different cell types, recent studies point to important roles for TCF4 in the nervous system. Specifically, human TCF4 gene is implicated in susceptibility to schizophrenia and TCF4 haploinsufficiency is the cause of the Pitt-Hopkins mental retardation syndrome. However, the structure, expression and coding potential of the human TCF4 gene have not been described in detail. PRINCIPAL FINDINGS: In the present study we used human tissue samples to characterize human TCF4 gene structure and TCF4 expression at mRNA and protein level. We report that although widely expressed, human TCF4 mRNA expression is particularly high in the brain. We demonstrate that usage of numerous 5' exons of the human TCF4 gene potentially yields in TCF4 protein isoforms with 18 different N-termini. In addition, the diversity of isoforms is increased by alternative splicing of several internal exons. For functional characterization of TCF4 isoforms, we overexpressed individual isoforms in cultured human cells. Our analysis revealed that subcellular distribution of TCF4 isoforms is differentially regulated: Some isoforms contain a bipartite nuclear localization signal and are exclusively nuclear, whereas distribution of other isoforms relies on heterodimerization partners. Furthermore, the ability of different TCF4 isoforms to regulate E-box controlled reporter gene transcription is varied depending on whether one or both of the two TCF4 transcription activation domains are present in the protein. Both TCF4 activation domains are able to activate transcription independently, but act synergistically in combination. CONCLUSIONS: Altogether, in this study we have described the inter-tissue variability of TCF4 expression in human and provided evidence about the functional diversity of the alternative TCF4 protein isoforms

Career orientation of secondary school students (m/f) in the Netherlands

In this paper, a new perspective is developed to promote a positive relationship between young people and technology. An in-depth study of the values young Dutch secondary school students feel are essential in their future profession was made. Following organisational psychologist Edgar Schein, we distinguish career anchors, each with their own core value. These core values show that differences between young people are considerable and explain why it is often so difficult to get grip on the decisive factors in the choice of a career. Although all girls have to deal with the masculine image of technology, they are not a homogenuous group as they pursue different values. Many of the anchors can be fullfilled by following study and career path in technology. However, current careers in technology are insufficiently associated with values such as creativity, service, autonomy and entrepeneurial. The educational system has been emphasizing the functional, expert anchor, but is gradually changing and preparing for the rise of the creative society that has been described by the economist Richard Florida. In contrast with Schein, we show that career anchors can already be indentified in secondary school students and added a new anchor identity.Applied Science