Dissection of the Transformation of Primary Human Hematopoietic Cells by the Oncogene NUP98-HOXA9

NUP98-HOXA9 is the prototype of a group of oncoproteins associated with acute myeloid leukemia. It consists of an N-terminal portion of NUP98 fused to the homeodomain of HOXA9 and is believed to act as an aberrant transcription factor that binds DNA through the homeodomain. Here we show that NUP98-HOXA9 can regulate transcription without binding to DNA. In order to determine the relative contributions of the NUP98 and HOXA9 portions to the transforming ability of NUP98-HOXA9, the effects of NUP98-HOXA9 on primary human CD34+ cells were dissected and compared to those of wild-type HOXA9. In contrast to previous findings in mouse cells, HOXA9 had only mild effects on the differentiation and proliferation of primary human hematopoietic cells. The ability of NUP98-HOXA9 to disrupt the differentiation of primary human CD34+ cells was found to depend primarily on the NUP98 portion, whereas induction of long-term proliferation required both the NUP98 moiety and an intact homeodomain. Using oligonucleotide microarrays in primary human CD34+ cells, a group of genes was identified whose dysregulation by NUP98-HOXA9 is attributable primarily to the NUP98 portion. These include RAP1A, HEY1, and PTGS2 (COX-2). Their functions may reflect the contribution of the NUP98 moiety of NUP98-HOXA9 to leukemic transformation. Taken together, these results suggest that the effects of NUP98-HOXA9 on gene transcription and cell transformation are mediated by at least two distinct mechanisms: one that involves promoter binding through the homeodomain with direct transcriptional activation, and another that depends predominantly on the NUP98 moiety and does not involve direct DNA binding

Deterrence in Cyberspace: An Interdisciplinary Review of the Empirical Literature

The popularity of the deterrence perspective across multiple scientific disciplines has sparked a lively debate regarding its relevance in influencing both offenders and targets in cyberspace. Unfortunately, due to the invisible borders between academic disciplines, most of the published literature on deterrence in cyberspace is confined within unique scientific disciplines. This chapter therefore provides an interdisciplinary review of the issue of deterrence in cyberspace. It begins with a short overview of the deterrence perspective, presenting the ongoing debates concerning the relevance of deterrence pillars in influencing cybercriminals’ and cyberattackers’ operations in cyberspace. It then reviews the existing scientific evidence assessing various aspects of deterrence in the context of several disciplines: criminology, law, information systems, and political science. This chapter ends with a few policy implications and proposed directions for future interdisciplinary academic research

Algorithms and Logic as Programming Primers

To adapt all-immersive digitalization, the Finnish National Curriculum 2014 (FNC-2014) ‘digi-jumps’ by integrating programming into elementary education. However, applying the change to mathematics teachers’ everyday praxis is hindered by a too high-level specification. To elaborate FNC-2014 into more concrete learning targets, we review the computer science syllabi of countries that are well ahead, as well as the education recommendations set by computer science organizations, such as ACM and IEEE. The whole mathematics syllabus should be critically viewed in the light of these recommendations and feedback collected from software professionals and educators. The feedback reveals an imbalance between supply and demand, i.e., what is over-taught versus under-taught, from the point of the requirements of current working life. The surveyed software engineers criticize the unnecessary surplus of calculus and differential equations, i.e., continuous mathematics. In contrast, the emphasis should shift more towards algorithms and data structures, flexibility in handling multiple data representations, and logic: in short – discrete mathematics. The ground for discrete mathematics should be prepared early enough, started already from primary level and continued consistently throughout the secondary till tertiary education. This paper aims to contribute to the further refinement of the mathematics syllabus by proposing such a discrete mathematics subset that especially supports the needs of computer science education, the focus being on algorithms and data structures, and logic in particular.peerReviewe