The Conserved Domain CR2 of Epstein–Barr Virus Nuclear Antigen Leader Protein Is Responsible Not Only for Nuclear Matrix Association but Also for Nuclear Localization

AbstractThere is a growing body of evidence for the importance of the nuclear matrix in various nuclear events including gene expression and DNA replication. Epstein–Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) is a nuclear matrix-associated protein that has been suggested to play an important role in EBV-induced transformation. To define the biological significance of the association of EBNA-LP with the nuclear matrix, we mapped the domain of EBNA-LP responsible for nuclear matrix association and investigated the functions of the EBNA-LP mutant mutagenized by substitution of alanines for the cluster of arginine residues in the mapped region. The results of the present study were as follows. (i) Transiently expressed EBNA-LP in COS-7 or BOSC23 cells was associated with the nuclear matrix, similarly to that in EBV-infected B cells. (ii) Mutational analysis of EBNA-LP revealed that a 10-amino acid segment of EBNA-LP is critical for nuclear matrix association of the protein. Interestingly, the identified region overlapped with the region CR2 of EBNA-LP conserved among a subset of primate gammaherpesviruses. The identified segment is referred to as EBNA-LP NMTS (nuclear matrix targeting signal). (iii) The EBNA-LP mutant with the arginine to alanine substitutions in NMTS was no longer localized not only to the nuclear matrix but also to the nucleus. (iv) The EBNA-LP mutant lacked its ability to coactivate EBNA-2-dependent transactivation. These results indicated that EBNA-LP needs to be localized in the nucleus and/or associated with the nuclear matrix through CR2 to elicit its function such as the coactivation of the EBNA-2-dependent transcriptional activation

EXTRACTING THE SOFTWARE ELEMENTS AND DESIGN PATTERNS FROM THE SOFTWARE FIELD

Abstract: Deriving the class structure of object-oriented software has been studied intensively. We have proposed a methodology to divide the conceptual model used in the object-oriented analysis into basic elements, such as classes, attributes, methods, relations, and to define constraint characteristics and constructing operations on each element. In the methodology, we have applied the field theory in the quantum physics to software and proposed the software field concepts (Ohki and Kambayashi, 2002a). Our thesis is that software is a kind of fields in which software elements, such as methods and attributes, interact each other to produce certain behavioral patterns. The methodology explains well the characteristics of class libraries (Ohki and Kambayashi, 2002b). Once the software elements are extracted from the software field, the methodology allows constructing design patterns from the characteristics of the elements (Ohki and Kambayashi, 2002a). Although we defined the extract operations to elicit the software elements, we failed to show that those operations have reasons and are correct (Ohki and Kambayashi, 2002a). In order to overcome this problem, in this paper, we introduce the distribution functions to represent the software elements, and to formulate the interactions of the functions. Using the distribution functions and the interactions between them, we have succeeded to suggest how to extract the software elements from the software field, and how to derive the design patterns by using the characteristics of the extract elements. This paper first describes the basic concepts of the software field, and then introduces the distribution functions to represent the software elements. In the latter part of this paper describes that it is applicable to derive typical design patterns.