Etoposide: four decades of development of a topoisomerase II inhibitor

Podophyllin-containing materials have been used as folk medicines for centuries. In the 1950s, scientists began a search to identify a more effective podophyllotoxin derivative. These efforts eventually resulted in the development of a new class of antineoplastic agents which target the DNA unwinding enzyme, topoisomerase II. The history of the development of one of the first identified topoisomerase II inhibitors, etoposide, is reviewed in this paper. Critical developments in etoposide's mechanism of action, pharmacology and administration schedule are summarised. The clinical benefits of the recently marketed etoposide prodrug, etoposide phosphate (Etopophos) are also detailed. The current status of other clinically approved anticancer agents which target topoisomerase II is briefly reviewed.     

An abrupt transition in colony founding behaviour in the ant Messor pergandei

Transitions in behaviour across a continuous distribution of organisms can provide valuable information on how variation in behaviour is maintained. We used analyses developed for interspecific hybrid zones to examine geographic variation in colony founding strategy in the desert seed-harvester ant, Messor pergandei. Newly mated females initiate new colonies either alone (haplometrosis) or cooperatively with other foundresses (pleometrosis). The incidence of these founding strategies were surveyed across the species' range and found to occur in geographically distinct regions joined by a narrow transition zone. Foundresses collected from haplometrotic sites were more likely to display aggression and found solitary nests than foundresses from pleometrotic sites, suggesting that geographical variation in metrosis is due to genotypic divergence. Foundresses from transitional sites were generally not aggressive and tended to co-found nests in the laboratory, yet rarely formed associations in the field. Such an abrupt shift in behaviour indicates that variation in colony founding strategy is maintained by selection rather than the result of secondary contact of neutral characters. Level of aggression displays a wider cline than founding strategy and is likely under selection only when accompanied by active strategy preference. Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.     

Monocular enucleation prevents retinal ganglion-cell loss following neonatal visual cortex damage in cats

Studies were conducted to assess the utility of free solution capillary electrophoresis (CE) for monitoring the effects of selected excipients on the thermal denaturation of a model protein (Ribonuclease A, RNase A) at low pH. Thermal denaturation/unfolding experiments were conducted via temperature-controlled CE using a run buffer of 20 mM citric acid in the pH range of 2.3-3.1, with a marker peptide incorporated to correct for temperature-induced changes in endoosmotic flow. The effects of selected excipients on the thermal unfolding of RNase A were then evaluated by adding either sorbitol, sucrose, polyethylene glycol 400 (PEG 400) or 2-methyl-2,4-pentanediol (MPD) to the electrophoretic run buffer (pH 2.3). Confirmatory denaturation experiments were conducted under the same solution conditions using circular dichroism (CD) spectropolarimetry. Using temperature-controlled CE, an increase in solution pH from 2.3 to 2.7 and 3.1 resulted in an increase in transition temperatures of RNase A by approximately 8 and 13 degrees C, respectively. Similar shifts in transition temperatures were observed when thermal denaturation transitions were monitored by far-UV CD. Sorbitol (0.55-1.1 M) and sucrose (0.55 M) each shifted the denaturation transition temperatures of RNase A to higher values, whereas PEG 400 and MPD had minimal effect on the unfolding transition midpoint at the concentrations evaluated (0.55 M for each). The observed changes in the transition temperatures for RNase A as a function of pH and selected excipients were similar when measured by either CE or far-UV CD. These results support the utility of CE for monitoring the effects of neutral excipients on the thermal denaturation of a model protein under selected conditions. The widespread utility of the technique may be limited by the narrow temperature range of most commercial CE instruments and the need to use extreme pH conditions to monitor the complete denaturation transition.     

Locality-preserving hash functions for general purpose parallel computation

Consider the problem of efficiently simulating the shared-memory parallel random access machine (PRAM) model on massively parallel architectures with physically distributed memory. To prevent network congestion and memory bank contention, it may be advantageous to hash the shared memory address space. The decision on whether or not to use hashing depends on (1) the communication latency in the network and (2) the locality of memory accesses in the algorithm.We relate this decision directly to algorithmic issues by studying the complexity of hashing in the Block PRAM model of Aggarwal, Chandra, and Snir, a shared-memory model of parallel computation which accounts for communication locality. For this model, we exhibit a universal family of hash functions having optimal locality. The complexity of applying these hash functions to the shared address space of the Block PRAM (i.e., by permuting data elements) is asymptotically equivalent to the complexity of performing a square matrix transpose, and this result is best possible for all pairwise independent universal hash families. These complexity bounds provide theoretical evidence that hashing and randomized routing need not destroy communication locality, addressing an open question of Valiant.This work was started when the author was a student at Oxford University, supported by a National Science Foundation Graduate Fellowship and a Rhodes Scholarship. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author and do not necessarily reflect the views of the National Science Foundation or the Rhodes Trust.     

Clinical applications of anticancer drugs targeted to topoisomerase II

Agents which 'poison' the enzyme topoisomerase II, have proven to be useful drugs for cancer treatment. Six antineoplastic drugs, which target topoisomerase II (doxorubicin, daunorubicin, idarubicin, mitoxantrone, etoposide and teniposide) are currently approved for clinical use in the United States. In this paper, the strategies and goals of cancer chemotherapy are summarized for the non-clinician. The use, pharmacology and toxicity of each of the six currently approved topoisomerase II inhibiting agents are reviewed.     

Fibular shortening in poliomyelitis

We have determined the nucleotide and encoded amino acid sequences of the capsid, membrane precursor, membrane, envelope, and nonstructural NS1 protein genes of a dengue-2 virus (D2-04) isolated from a patient in Hainan, China. The sequenced region contains a gene organization similar to that of other flaviviruses. The overall amino acid sequence similarity between D2-04 and other dengue-2 viruses is greater than 92%, whereas that between D2-04 and members of the other dengue serotypes is about 65%.     

Intelligent control of doubly‐fed induction generator systems using PIDNNs

An intelligent control for a stand‐alone doubly‐fed induction generator (DFIG) system using a proportional‐integral‐derivative neural network (PIDNN) is proposed in this study. This system can be applied as a stand‐alone power supply system or as the emergency power system when the electricity grid fails for all sub‐synchronous, synchronous, and super‐synchronous conditions. The rotor side converter is controlled using field‐oriented control to produce 3‐phase stator voltages with constant magnitude and frequency at different rotor speeds. Moreover, the grid side converter, which is also controlled using field‐oriented control, is primarily implemented to maintain the magnitude of the DC‐link voltage. Furthermore, the intelligent PIDNN controller is proposed for both the rotor and grid side converters to improve the transient and steady‐state responses of the DFIG system for different operating conditions. Both the network structure and online learning algorithm are introduced in detail. Finally, the feasibility of the proposed control scheme is verified through experimentation. Copyright © 2011 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society     

Distributed election in complete networks

An improved version of Afek and Gafni's synchronous algorithm for distributed election in complete networks is given and anO(n) expected message complexity is shown. M.Y. Chan received her Ph.D. in 1988 from the University of Hong Kong, and her M.S. and B.A. degrees in computer science from the University of California, San Diego in 1980 and 1981, respectively. She is currently an Assistant Professor at the University of Texas at Dallas. Francis Y.L. Chin (S71-M76-SM85) received the B.Sc. degree in engineering science from the University of Toronto, Toronto, Canada, in 1972, and the M.S., M.A., and Ph.D. degrees in electrical engineering and computer science from Princeton University, New Jersey, in 1974, 1975, and 1976, respectively. Since 1975, he has taught at the University of Maryland, Baltimore Country, University of California, San Diego, University of Alberta, and Chinese University of Hong Kong. He is currently Head of the Department of Computer Science, University of Hong Kong. He has served as a program co-chairman of the 1988 International Conference on Computer Processing of Chinese and Oriental Languages (Toronto) and the International Computer Science Conference '88 (Hong Kong). His current research interests include algorithm design and analysis, parallel and distributed computing.     

Optically pumped submillimeter gas lasers and the prospects for constructing space-qualifiable LO systems

An optically pumped submillimeter laser operating in the 500 μm (600 GHz) to 100 μm (3 THz) spectral range is the primary and, at present, the only available local oscillator (LO) source for laboratory and astronomical heterodyne applications for this wavelength region. A short review of the state-of-the-art of submillimeter lasers as LO sources, with an emphasis given to receiver systems designed for airborne heterodyne observations, will be presented. The characteristics and prospects for constructing a spacequalifiable laser LO system will also be given.     

An improved algorithm for finding the median distributively

Given two processes, each having a total-ordered set ofn elements, we present a distributed algorithm for finding median of these 2n elements using no more than logn +O(logn) messages, but if the elements are distinct, only logn +O(1) messages will be required. The communication complexity of our algorithm is better than the previously known result which takes 2 logn messages.