We have tested the effect of the individual DNase I hypersensitive site (HS) regions of the globin locus control region (LCR) on the developmental expression pattern of the human 7 and [3 genes in transgenic mice. The results show that HS3 is the most active site during the embryonic period. It is also the only site capable of high level expression of the 7 genes during fetal hematopoiesis, in a population of cells that are capable of expressing both the 7 and [3 genes. Region HS4 shows the highest activity during the adult stage and expresses the 7 genes only at low levels during the embryonic period. HS2 drives equivalent levels of 7 or [3 transgene expression throughout development. HS1 has a similar pattern to HS2, although the activity of HS1 is very low. From these results we conclude that the HS regions have distinct developmental specificities and suggest that in the complete LCR they interact with each other to form a larger complex which, in turn, interacts with the globin genes.

We have shown that the promoter of the human beta‐globin gene contains three regions in addition to the known CAC, CAAT and TATA box regions that are important for the induction of transcription in erythroid cells. By using DNaseI footprinting and gel mobility shift assays we were able to show that two of these regions bind the erythroid specific nuclear factor NF‐E1 (and ubiquitous factors). The third region binds a ubiquitous CAAT‐box factor (CP1). Deletion experiments suggest that only the combination of NF‐E1 and CP1 binding sites, but not each of the sites alone, are capable of mediating the induction of transcription of a minimal (CAC, CAAT, TATA box) beta‐globin promoter in mouse erythroleukaemia (MEL) cells.

Retrovirus-mediated gene transfer into hematopoietic cells may provide a means of treating both inherited and acquired diseases involving hematopoietic cells. Implementation of this approach for disorders resulting from mutations affecting the 8-globin gene (e.g., P-thalassemia and sickle cell anemia), however, has been hampered by the inability to generate recombinant viruses able to efficiently and faithfully transmit the necessary sequences for appropriate gene expression. We have addressed this problem by carefully examining the interactions between retroviral and j3-globin gene sequences which affect vector transmission, stability, and expression. First, we examined the transmission properties ofa large number ofdifferent recombinant proviral genomes which vary both in the precise nature of vector, 18-globin structural gene, and locus control region (LCR) core sequences incorporated and in the placement and orientation of those sequences. Through this analysis, we identified one specific vector, termed Mj36L, which carries both the human ,8-globin gene and core elements HS2, HS3, and HS4 from the LCR and faithfully transmits recombinant proviral sequences to cells with titers greater than 106 per ml. Populations of murine erythroleukemia (MEL) cells transduced by this virus expressed levels of human j8-globin transcript which, on a per gene copy basis, were 78% of the levels detected in an MEL-derived cell line, Hull, which carries human chromosome 11, the site of the 13-globin locus. Analysis of individual transduced MEL cell clones, however, indicated that, while expression was detected in every clone tested (n = 17), the levels of human j8-globin treatment varied between 4% and 146% of the levels in Hull. This clonal variation in expression levels suggests that small ,-globin LCR sequences may not provide for as strict chromosomal position-independent expression of 18-globin as previously suspected, at least in the context of retrovirus-mediated gene transfer.

This paper is a first introduction to the concept of using Global Navigation Satellite Systems (GNSS) as illuminators of opportunity in a passive bistatic real-time radar system for maritime target indication applications. An overview of the system concept and the signal processing algorithms for Moving Target Indication (MTI) is provided. To verify the feasibility of the system implementation as well as test the developed signal processing algorithms, an experimental test bed was developed and the appropriate experimental campaign with the new Galileo satellites and a ferry as the target was carried out. The results confirm the system concept and its potential for multi-static operation, with the ferry being detected simultaneously by two satellites.