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

Samlet plan for utslipp til vann fra steinindustrien (larvikittprodusentene) i Larvik, Del 1: Resipientundersøkelser 2006-2008 (Tekstdel)

Det er gjennomført resipientundersøkelser i vannforekomster som mottar avrenning fra Larvikittproduksjonen i Tjølling og Brunlanes i Larvik kommune. I alt 130 lokaliteter omfattende bekker, elver, innsjøer og fjorder er undersøkt gjennom en periode på to år. Vannforekomstene er undersøkt for turbiditet (grumsethet), vannkjemi, alger, bunnfauna, og fisk. Selv om påvirkningen visuelt sett kan virke betydelig, var den økologiske effekten overraskende liten. Kun i de sterkest påvirkede lokaliteter kunne man finne klare negative effekter på vannøko­logien. Dette gjaldt innsjøene Mørjetjern, Bålsrudtjern, og i noe mindre grad Torpevannet. Det var ingen økolog­iske eller bruksmessige påvirkninger i Hallevannet. Nordre del av Varildfjorden i Viksfjord, var periodevis sterk påvirket av slamtilførsel, men noen økologisk effekt synes ikke utslippet å ha. Det samme kan sies om Mørje­fjorden, innerst i Sildevika og ut for Kastet. I ekelte av de små bekkene var det negative effekter både på begroing, bunndyr og fisk. Dette gjaldt øverst i Tveidalsbekken, Mørjebekken, Askedalsbekken, Håkestadbekken, og Haslebekken. Det kunne ikke påvises negative økologiske effekter i de viktige lokalitetene som Istreelva, Mørjerød­bekken, Mørjetjernbekken, og Eikedalsbekken. Kun få år etter at et brudd er avsluttet, avtar konsentra­sjonene av forurensninger i avrenningen til uproblematiske nivåer. Med tanke på eutrofieringsvirkninger ble biotilgjengeligheten av fosfor i finknust larvikitt funnet å være lav, omtrent som fra turbid isbreavrenning og bare ca 1/5 av biotilgjengeligheten av fosfor fra erosjonsavrenning fra dyrket mark. Larvikitt inneholder ikke nitrogen. Alu­miniums­innholdet i larvikitten ble ikke funnet å kunne opptre i giftige former ved den pH og ionestyrke som er tilstede i de aktuelle resipientene.Larvikittprodusentenes forening (LPF

Samlet plan for utslipp til vann fra steinindustrien (larvikittprodusentene) i Larvik Del 1 Resipientundersøkelser 2006-2008 (Datarapport)

Rapporten inneholder: Stasjonsregister med koordinater Alle stasjonene vist på karter Alle fysiske, kjemiske, og biologiske primærdata i tabellerLarvikittprodusentenes Forening (LPF

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

Association of Transcription Factor 4 (TCF4) variants with schizophrenia and intellectual disability

Genome wide association studies (GWAS) have revolutionized the study of complex diseases and have uncovered common genetic variants associated with an increased risk for major psychiatric disorders. A recently published schizophrenia GWAS replicated earlier findings implicating common variants in Transcription factor 4 (TCF4) as susceptibility loci for schizophrenia. By contrast, loss of function TCF4 mutations, although rare, cause Pitt-Hopkins syndrome (PTHS); a disorder characterized by intellectual disability (ID), developmental delay and behavioral abnormalities. TCF4 mutations have also been described in individuals with ID and non-syndromic neurodevelopmental disorders. TCF4 is a member of the basic helix-loop-helix (bHLH) family of transcription factors that regulate gene expression at E-box-containing promoters and enhancers. Accordingly, TCF4 has an important role during brain development and can interact with a wide array of transcriptional regulators including some proneural factors. TCF4 may, therefore, participate in the transcriptional networks that regulate the maintenance and differentiation of distinct cell types during brain development. Here, we review the role of TCF4 variants in the context of several distinct brain disorders associated with impaired cognition