The initiation of simian virus 40 DNA replication in vitro

DNA replication is a complicated process that is largely regulated during stages of initiation. The Siman Virus 40 in vitro replication system has served as an excellent model for studies of the initiation of DNA replication, and its regulation, in eukaryotes. Initiation of SV40 replication requires a single viral protein termed T-antigen, all other proteins are supplied by the host. The recent determination of the solution structure of the T-antigen domain that recognizes the SV40 origin has provided significant insights into the initiation process. For example, it has afforded a clearer understanding of origin recognition, T-antigen oligomerization, and DNA unwinding. Furthermore, the Simian virus 40 in vitro replication system has been used to study nascent DNA formation in the vicinity of the viral origin of replication. Among the conclusions drawn from these experiments is that nascent DNA synthesis does not initiate in the core origin in vitro and that Okazaki fragment formation is complex. These and related studies demonstrate that significant progress has been made in understanding the initiation of DNA synthesis at the molecular level.     

Distributed Sensing and Control Technology for Intelligent Civil Infrastructure Systems

Abstract: Sensing and control functions are the fundamental technologies on which many civil infrastructure control and monitoring systems are constructed. Early civil infrastructure control and monitoring systems employed a centralized computing model for sensor processing and actuator control. These systems required extensive wiring to route power, sensor, and control signals among the distributed input and output devices. Furthermore, the operation of the entire system depended on one or two computers. Abstractly, these civil infrastructure applications are a realtime data acquisition and control system. Due to the dramatic decrease in computing costs, it is now feasible to construct these real-time systems using dozens or even hundreds of distributed processors linked with a data communication network. This allows the controllers to be located adjacent to sensors and actuators, thereby reducing the need for long lengths of multiconductor wire that is subject to noise and breakage. Also, failure of a single processor does not necessarily cause the entire system to fail. This paper introduces the reader to a technology called LonWorks for constructing distributed sensing and control systems. The LonWorks technology is essentially a data communication network that links together extremely small computers called Neurons. Particular emphasis is placed on describing the communication architecture and emphasizing how the distributed Neuron communication processors are designed to ensure a truly modular and open architecture.     

Connecting the dots: Understanding the interrelated impacts of type,quality and children's awareness of design features and the mathematics content learning goals in digital math games and related learning outcomes

This study focused on an examination of how type, quality and children's awareness of design features in digital math games, along with an awareness of the mathematics goals of the game, were related to learning outcomes. We conducted a parallel conversion mixed methods study with 45 students in Grades 3 and 4 (ages 9–10). Students participated in clinical interviews using three digital math games. The results suggest a moderated mediation relationship in which the quality of the design features moderated the mediating impact of children's awareness of the game's design features, specifically when the child was aware of the mathematics content learning goal (MCLG) of the game. These findings show how important it is that design features are of high quality in a digital math game, and how this is intertwined with children's awareness of the features and the MCLG. When these variables intertwined in just the right way, the interactions between the children and the digital math game afforded mathematical learning growth.     

Evidence against a direct role for the induction of c-jun expression in the mediation of drug-induced apoptosis in human acute leukemia cells

Previous reports have demonstrated that a variety of anticancer drugs, e.g., 1-beta-D-arabinofuranosylcytosine (ara-C), mitoxantrone, etoposide, camptothecin, and cisplatin, induce the expression of c-jun oncogene in leukemic cells prior to producing internucleosomal DNA fragmentation and the morphological features of apoptosis. This has led to the impression that the induction of c-jun expression may be directly involved in the molecular signaling of the final common pathway of programmed cell death or apoptosis. In the present study, we examined the role of c-jun expression in three different settings of anticancer drug-induced apoptosis in human leukemic cells. First, exposure of human myeloid leukemia HL-60 cells to high-dose ara-C for 4 h produced internucleosomal DNA fragmentation preceded by c-jun induction. However, pretreatment of HL-60 cells with staurosporine, a protein kinase C inhibitor, repressed c-jun yet enhanced DNA fragmentation and apoptosis due to ara-C. Second, in human pre-B leukemia 697/BCL-2 cells which are transfected with the cDNA of the bcl-2 oncogene and overexpress p26BCL-2, although ara-C or mitoxantrone treatment caused greater c-jun induction than in the 697/neo cells, significantly reduced endonucleolytic DNA fragmentation and apoptosis was observed in 697/BCL-2 cells. Finally, taxol-induced internucleosomal DNA fragmentation and morphological features of apoptosis in HL-60 cells were not associated with the induction of c-jun expression. These lines of evidence indicate that the induction of c-jun expression may not have a direct role in the molecular signaling of anticancer drug-induced apoptosis, and that the anticancer drug-induced apoptosis can occur by a mechanism that does not involve the induction of c-jun expression.     

Combating coevolutionary disengagement by reducing parasite virulence

While standard evolutionary algorithms employ a static, absolute fitness metric, coevolutionary algorithms assess individuals by their performance relative to populations of opponents that are themselves evolving. Although this arrangement offers the possibility of avoiding long-standing difficulties such as premature convergence, it suffers from its own unique problems, cycling, over-focusing and disengagement. Here, we introduce a novel technique for dealing with the third and least explored of these problems. Inspired by studies of natural host-parasite systems, we show that disengagement can be avoided by selecting for individuals that exhibit reduced levels of "virulence", rather than maximum ability to defeat coevolutionary adversaries. Experiments in both simple and complex domains are used to explain how this counterintuitive approach may be used to improve the success of coevolutionary algorithms.     

Methodology for competitive strategy development

Fighting terrorists involves taking action against a highly adaptive and cunning adversary. In this competitive situation, however, those involved may have dissimilar objectives. Given this difference of purpose, selecting an optimal strategy to achieve one's objectives can be a complex task. Techniques from decision theory, and specifically value focused thinking (VFT), are proven approaches for developing creative strategies to yield better decisions. However, these methods are focused on one decision maker choosing an optimal decision without reference to the affect the decision has on other decision makers and without reference to the affect the decisions of others have on them. On-the-other-hand, techniques especially suited for analyzing competitive situations, such as game theory, assume strategies exist without guidance on how to develop the strategies. This paper presents a methodology to bridge this gap by providing a means to develop strategies in competitive situations where the objectives of those involved are not necessarily the same.     

Analysis of discrete-time Kalman filtering under incorrect noisecovariances

Analysis tools are developed that can be effectively used to study the performance degradation of a filter when incorrect models of the state and measurement noise covariances are used. For a linear time-variant system with stationary noise processes, it is shown that under certain stability conditions on the system model, the one-step prediction error covariance matrix will converge to a steady-state solution even when the filter gain is not optimal. On the other hand, if the state transition matrix has an unreachable mode outside a unit circle, then the modeling errors in the noise covariances may cause the filter to diverge. Bounds on the asymptotic filter performance are computed when the range of errors in the noise covariance matrices are known. Using simple examples, insights into the behavior of a Kalman filter under nonideal conditions are provided     

Interface contribution to GaAs/Ge heterojunction solar cellefficiency

A solar cell formed by growing a p-on-n AlGaAs/GaAs heteroface homojunction on a thin Ge substrate is studied by investigating the contribution of the GaAs/Ge heterostructure to the solar-cell efficiency. The existence of interface states is required in the absence of a Ge p-n junction to produce the photovoltaic effect with an open-circuit voltage enhancement as experimentally observed. Dark current-voltage characteristics of the GaAs/Ge heterojunction are calculated when the carrier transport is by thermionic emission and tunneling mechanisms. The evaluations correctly explain the observed changes of efficiency, the decrease of fill factor, the increase of open-circuit voltage, and the insignificant change of short-circuit current as compared to a GaAs/GaAs solar cell. It the short-circuit current from the heterojunction is on the order of 25 mA/cm², which is less than that of the p-n junction cell, the reduction of the solar cell efficiency is about 0.5-1.5% over a wide range of GaAs/Ge doping concentrations. Very few interface states tend to yield a diode-like dark I-V curve