Next Generation Network Management Technology

Today's telecommunications networks are becoming increasingly large, complex, mission critical and heterogeneous in several dimensions. For example, the underlying physical transmission facilities of a given network may be ﲭixed media (copper, fiber- optic, radio, and satellite); the sub networks may be acquired from different vendors due to economic, performance, or general availability reasons; the information being transmitted over the network may be ﲭultimedia (video, data, voice, and images) and, finally, varying performance criteria may be imposed e.g. data transfer may require high throughput while the others, whose concern is voice communications, may require low call blocking probability. For these reasons, future telecommunications networks are expected to be highly complex in their services and operations. Due to this growing complexity and the disparity among management systems for individual sub networks, efficient network management systems have become critical to the current and future success of telecommunications companies. This paper addresses a research and development effort which focuses on prototyping configuration management, since that is the central process of network management and all other network management functions must be built upon it. Our prototype incorporates ergonomically designed graphical user interfaces tailored to the network configuration management subsystem and to the proposed advanced object-oriented database structure. The resulting design concept follows open standards such as Open Systems Interconnection (OSI) and incorporates object oriented programming methodology to associate data with functions, permit customization, and provide an open architecture environment. A revised version of this technical report has been published in The 12th Symposium on Space Nuclear Power and Propulsion/Commercialization, pp. 75-82, Albuquerque, NM, January 8-12, 1995.</ul

Hyperoxia impairs postnatal alveolar epithelial development via NADPH oxidase in newborn mice

Hyperoxia disrupts postnatal lung development in part through inducing inflammation. To determine the contribution of leukocyte-derived reactive oxygen species, we exposed newborn wild-type and NADPH oxidase p47phox subunit null (p47phox−/−) mice to air or acute hyperoxia (95% O2) for up to 11 days. Hyperoxia-induced pulmonary neutrophil influx was similar in wild-type and p47−/− mice at postnatal days (P) 7 and 11. Macrophages were decreased in wild-type hyperoxia-exposed mice compared with p47phox−/− mice at P11. Hyperoxia impaired type II alveolar epithelial cell and bronchiolar epithelial cell proliferation, but depression of type II cell proliferation was significantly less in p47−/− mice at P3 and P7, when inflammation was minimal. We found reciprocal results for the expression of the cell cycle inhibitor p21cip/waf in type II cells, which was induced in 95% O2-exposed wild-type mice, but significantly less in p47phox−/− littermates at P7. Despite partial preservation of type II cell proliferation, deletion of p47phox did not prevent the major adverse effects of hyperoxia on alveolar development estimated by morphometry at P11, but hyperoxia impairment of elastin deposition at alveolar septal crests was significantly worse in wild-type vs. p47phox−/− mice at P11. Since we found that p47phox is expressed in a subset of alveolar epithelial cells, its deletion may protect postnatal type II alveolar epithelial proliferation from hyperoxia through effects on epithelial as well as phagocyte-generated superoxide

p53-mediated apoptosis requires inositol hexakisphosphate kinase-2

Inositol pyrophosphates have been implicated in numerous biological processes. Inositol hexakisphosphate kinase-2 (IP6K2), which generates the inositol pyrophosphate, diphosphoinositol pentakisphosphate (IP7), influences apoptotic cell death. The tumor suppressor p53 responds to genotoxic stress by engaging a transcriptional program leading to cell-cycle arrest or apoptosis. We demonstrate that IP6K2 is required for p53-mediated apoptosis and modulates the outcome of the p53 response. Gene disruption of IP6K2 in colorectal cancer cells selectively impairs p53-mediated apoptosis, instead favoring cell-cycle arrest. IP6K2 acts by binding directly to p53 and decreasing expression of proarrest gene targets such as the cyclin-dependent kinase inhibitor p21

Casein kinase-2 mediates cell survival through phosphorylation and degradation of inositol hexakisphosphate kinase-2

The inositol pyrophosphate, diphosphoinositol pentakisphosphate, regulates p53 and protein kinase Akt signaling, and its aberrant increase in cells has been implicated in apoptosis and insulin resistance. Inositol hexakisphosphate kinase-2 (IP6K2), one of the major inositol pyrophosphate synthesizing enzymes, mediates p53-linked apoptotic cell death. Casein kinase-2 (CK2) promotes cell survival and is upregulated in tumors. We show that CK2 mediated cell survival involves IP6K2 destabilization. CK2 physiologically phosphorylates IP6K2 at amino acid residues S347 and S356 contained within a PEST sequence, a consensus site for ubiquitination. HCT116 cells depleted of IP6K2 are resistant to cell death elicited by CK2 inhibitors. CK2 phosphorylation at the degradation motif of IP6K2 enhances its ubiquitination and subsequent degradation. IP6K2 mutants at the CK2 sites that are resistant to CK2 phosphorylation are metabolically stable

Protein pyrophosphorylation by inositol pyrophosphates is a posttranslational event

In a previous study, we showed that the inositol pyrophosphate diphosphoinositol pentakisphosphate (IP7) physiologically phosphorylates mammalian and yeast proteins. We now report that this phosphate transfer reflects pyrophosphorylation. Thus, proteins must be prephosphorylated by ATP to prime them for IP7 phosphorylation. IP7 phosphorylates synthetic phosphopeptides but not if their phosphates have been masked by methylation or pyrophosphorylation. Moreover, IP7 phosphorylated peptides are more acid-labile and more resistant to phosphatases than ATP phosphorylated peptides, indicating a different type of phosphate bond. Pyrophosphorylation may represent a novel mode of signaling to proteins