Sydis and the voice/data terminal craze of 1984

In 1984, computing firms saw integrated voice/data terminals (IVDTs) as the solution to the proliferation of new forms of executive communication. The Sydis VoiceStation was hailed as the best of this new class of office machine but, like all IVDTs, it failed. Sydis succumbed to "integration stress," one danger of product development driven by the urge to integrate traditionally discrete functions. Sydis also failed from poor integration of financial and market actors.     

Utility function of TCP

Understanding the TCP congestion control mechanism from a global optimization point of view is not only important in its own right, but also crucial to the design of other transport layer traffic control protocols with provable properties. In this paper, we derive a global utility function and the corresponding optimal control law, known as TCP control law, which maximizes the global utility. The TCP control law captures the essential behaviors of TCP, including slow start, congestion avoidance, and the binary nature of congestion feedback in TCP. We find that the utility function of TCP is linear in the slow start phase and is proportional to the additive increase rate and approaches the well-known logarithm function as the data rate becomes large in the congestion avoidance phase. We also find that understanding the slow start phase with a fixed threshold is critical to the design of new transport layer control protocols to enable quality of service features. Finally, as an application, we design a Minimum Rate Guaranteed (MRG) traffic control law that shares the same utility function as the TCP control law. Our simulation study of the MRG control law indicates that it is indeed TCP friendly and can provide minimum rate guarantee as long as the percentage of network resource consumed by the MRG flows is moderately small.     

Product Review: Near-IR gets the job done

Infrared brings to mind spectra with narrow, well-separated peaks; anybody expecting something similar from near-IR needs to think again.     

Focus: DNA microarrays in toxicology

Gene expression analysis promises to change toxicology.     

Radiation sensitivity of an Escherichia coli mutant lacking NADP+-dependent isocitrate dehydrogenase

Ionizing radiation induces the production of reactive oxygen species, which play an important causative role in radiation damage. NADP+-dependent isocitrate dehydrogenase (ICDH) in Escherichia coli produces NADPH, an essential reducing equivalent for the antioxidant system. The protective role of ICDH against ionizing radiation in E. coli was investigated in wild-type and ICDH-deficient strains. Upon exposure to ionizing radiation, the viability was lower and the lipid peroxidation was higher in mutant cells compared to wild-type cells. Activities of key antioxidant enzymes such as superoxide dismutase, catalase, glutathione reductase, and glucose-6-phosphate dehydrogenase were decreased by irradiation in both cells. Results suggest that ICDH plays an important role as an antioxidant enzyme in cellular defense against ionizing radiation.     

Ectopic expression of pRb2/p130 suppresses the tumorigenicity of the c-erbB-2-overexpressing SKOV3 tumor cell line

We investigated the in vitro and in vivo effects of the ectopic expression of the pRb2/p130 cell cycle regulator on c-erbB-2-associated tumorigenicity. SKOV3 ovarian cancer cells, which display c-erbB-2 gene amplification and oncoprotein (p185HER2) overexpression, were stably transfected with a plasmid containing the coding sequence for human wild-type pRb2/p130 (wtRb2), or with pcDNA3 empty vector. Three wtRb2-transfected clones (cl. 24, ci. 49, cl. 100) and one empty vector-transfected clone (cl. mock) were randomly picked and further analysed. Western blot analysis revealed high levels of pRb2/p130 in the three clones compared to mock cells. Levels of p185HER2 and the extent of its tyrosine phosphorylation were similar in all transfectant clones, as were levels of pRb1 and p107. In anchorage-independent growth assays, the number of colonies from wtRb2 clone-transfectants was about 90% less than that arising from mock cells (P<0.001). Tumor take rates of the three wtRb2-transfected clones xenografted in nu/nu mice were much lower than those of mock cells, and tumor volume was decreased by 80% (P<0.001). A mutant version of pRb2/p130 deleted of the pocket region (mut-Rb2) was also transfected into SKOV3 cells and studied in parallel with the wtRb2-transfected and pcDNA empty vector-transfected bulk populations. mut-Rb2 transfected cells showed no inhibition of in vitro colony formation and were fully tumorigenic. Together, these findings indicate that Rb2 acts as a tumor suppressor gene in vivo and in vitro in SKOV3 cells and that the intact pocket region is required for the suppressor activity.     

Cascades of mammalian caspase activation in the yeast Saccharomyces cerevisiae

Caspases (aspartate-specific cysteine proteases) play a critical role in the execution of the mammalian apoptotic program. To address the regulation of human caspase activation, we used the yeast Saccharomyces cerevisiae, which is devoid of endogenous caspases. The apical procaspases, -8beta and -10, were efficiently processed and activated in yeast. Although protease activity, per se, was insufficient to drive cell death, caspase-10 activity had little effect on cell viability, whereas expression of caspase-8beta was cytotoxic. This lethal phenotype was abrogated by co-expression of the pan-caspase inhibitor, baculovirus p35, and by mutation of the active site cysteine of procaspase-8beta. In contrast, autoactivation of the executioner caspase-3 and -6 zymogens was not detected. Procaspase-3 activation required co-expression of procaspase-8 or -10. Surprisingly, activation of procaspase-6 required proteolytic activities other than caspase-8, -10, or -3. Caspase-8beta or -10 activity was insufficient to catalyze the maturation of procaspase-6. Moreover, a constitutively active caspase-3, although cytotoxic in its own right, was unable to induce the processing of wild-type procaspase-6 and vice versa. These results distinguish sequential modes of activation for different caspases in vivo and establish a yeast model system to examine the regulation of caspase cascades. Moreover, the distinct terminal phenotypes induced by various caspases attest to differences in the cellular targets of these apoptotic proteases, which may be defined using this system.     

Experimental characterization of focusing by high-numerical-aperture zone plates

High-numerical-aperture zone plates have important applications in high-resolution optical maskless lithography as well as scanning confocal microscopy. We describe two methods to experimentally characterize the focusing properties, i.e., the point-spread function, of such diffractive lenses. The first method uses spot exposures in photoresist and the second uses a conventional knife-edge scan. The experimental results agree well with rigorous theoretical calculations.