Increased assembly of cytoskeletal proteins associated with the transformation of human liver cells into fibroblast-like cells.

A topoisomerase II inhibitor, novobiocin, and a deacetylase inhibitor, butyrate, synergistically transformed human liver cells into fibroblast-like cells. This morphological change was associated with an increased production of procollagen type III peptide and a simultaneous assembly of actin, tubulin, vimentin and cytokeratin. Novobiocin and butyrate had no marked effect on the phosphorylation state of cytokeratin proteins, but synergistically enhanced [3H]acetate uptake. From these results, it can be speculated that protein acetylation plays an important role in inducing the assembly of cytoskeletal proteins and the morphological transformation of human liver cells.     

Newton's Easy Quadratures ``Omitted for the Sake of Brevity'

In the 1687 Principia, Newton gave a solution to the direct problem (given the orbit and center of force, find the central force) for a conic-section with a focal center of force (answer: a reciprocal square force) and for a spiral orbit with a polar center of force (answer: a reciprocal cube force). He did not, however, give solutions for the two corresponding inverse problems (given the force and center of force, find the orbit). He gave a cryptic solution to the inverse problem of a reciprocal cube force, but offered no solution for the reciprocal square force. Some take this omission as an indication that Newton could not solve the reciprocal square, for, they ask, why else would he not select this important problem? Others claim that ``it is child's play' for him, as evidenced by his 1671 catalogue of quadratures (tables of integrals). The answer to that question is obscured for all who attempt to work through Newton's published solution of the reciprocal cube force because it is done in the synthetic geometric style of the 1687 Principia rather than in the analytic algebraic style that Newton employed until 1671. In response to a request from David Gregory in 1694, however, Newton produced an analytic version of the body of the proof, but one which still had a geometric conclusion. Newton's charge is to find both ``the orbit' and ``the time in orbit.' In the determination of the dependence of the time on orbital position, t(r), Newton evaluated an integral of the form ∫dx/x <sup>n</sup> to calculate a finite algebraic equation for the area swept out as a function of the radius, but he did not write out the analytic expression for time t = t(r), even though he knew that the time t is proportional to that area. In the determination of the orbit, θ (r), Newton obtained an integral of the form ∫dx/√(1−x<sup>2</sup>) for the area that is proportional to the angle θ, an integral he had shown in his 1669 On Analysis by Infinite Equations to be equal to the arcsin(x). Since the solution must therefore contain a transcendental function, he knew that a finite algebraic solution for θ=θ(r) did not exist for ``the orbit' as it had for ``the time in orbit.' In contrast to these two solutions for the inverse cube force, however, it is not possible in the inverse square solution to generate a finite algebraic expression for either ``the orbit' or ``the time in orbit.' In fact, in Lemma 28, Newton offers a demonstration that the area of an ellipse cannot be given by a finite equation. I claim that the limitation of Lemma 28 forces Newton to reject the inverse square force as an example and to choose instead the reciprocal cube force as his example in Proposition 41. (Received August 14, 2002) Published online March 26, 2003 Communicated by G. Smith     

MeV Pb离子在非晶Si中的射程离散──离子束混合和增强扩散的影响

１．０ＭｅＶ２０８Ｐｂ离子在非晶Ｓｉ中的投影射程ＲＰ和射程偏差ΔＲＰ作为注量和温度二者的函数用背散射法进行测定．注量的变化范围为５×１０１３～７×１０１４ｃｍ－２．注入是在室温和ｔ＝－１２０℃下完成的．由由实验所确定的投影射程，射程偏差与注量或温度无关，并且分别等于２９５和７２．２ｎｍ．与ＴＲＩＭ８６的计算结果相比较，发现ＲＰ的偏离为１８％，而ΔＲＰ的偏离为３６％．ＲＰ和ΔＲＰ二者与注量及温度的无关性，排除了所观察到的与ＴＲＩＭ的矛盾是由于注入期间辐射增强扩散或离子束混合效应而引起的解释。     

Purealidin A,a new cytotoxic bromotyrosine-derived alkaloid from the Okinawan marine spongePsammaplysilla purea

Summary A new bromotyrosine-derived alkaloid with antileukemic activity, purealidin A (5), has been isolated from the Okinawan marine spongePsammaplysilla purea and its chemical structure elucidated on the basis of the spectroscopic data.     

Aeromonas caviae: ecologic adaptation in the intestinal tract of infants coupled to adherence and enterotoxin production as factors in enteropathogenicity

Aeromonas caviae isolated from stools of diarrheic formula-fed infants and environmental sources produce acetic acid when grown in glucose broth, which is bactericidal (suicide phenomenon). A. caviae grows anaerobically in a minimal medium or under permissive conditions such as the intestinal tract of formula-fed infants. These isolates adhered to HEp-2 cells and produced a cytotoxic and a cytotonic enterotoxin which underscore their enteropathogenicity.     

Business Process Reengineering (BPR) Versus Outsourcing—Critical Perspectives

This article presents a case example involving the renaming of an organizational change process from BPR to outsourcing. The paper discusses the important ramifications of such a name change in that the recognition of outsourcing allowed an organizational commitment to counseling and termination advice. The paper discusses two ways of looking at the name change, one from a critical theory perspective and one from a realist perspective. It demonstrates how theory can provide useful yet markedly different interpretations of such organizational events. Critical theory operates from within what can be termed the transitive epistemological dimension, whereas critical realism tends to emphasize the importance of ontological issues. Each has important things to say about the situation and improves our understanding overall.     

Glycogen synthase kinase 3β and Alzheimer’s disease: pathophysiological and therapeutic significance

Alzheimer’s disease (AD) is a neurodegenerative disorder associated with cognitive and behavioral dysfunction and is the leading cause of dementia in the elderly. Several studies have implicated molecular and cellular signaling cascades involving the serine-threonine kinase, glycogen synthase kinase β(GSK-3β) in the pathogenesis of AD. GSK-3β may play an important role in the formation of neurofibrillary tangles and senile plaques, the two classical pathological hallmarks of AD. In this review, we discuss the interaction between GSK-3β and several key molecules involved in AD, including the presenilins, amyloid precursor protein, tau, and β-amyloid. We identify the signal transduction pathways involved in the pathogenesis of AD, including Wnt, Notch, and the PI3 kinase/Akt pathway. These may be potential therapeutic targets in AD. Received 19 December 2005; received after revision 24 January 2006; accepted 6 February 2006     

Common deletion polymorphisms in the human genome

The locations and properties of common deletion variants in the human genome are largely unknown. We describe a systematic method for using dense SNP genotype data to discover deletions and its application to data from the International HapMap Consortium to characterize and catalogue segregating deletion variants across the human genome. We identified 541 deletion variants (94% novel) ranging from 1 kb to 745 kb in size; 278 of these variants were observed in multiple, unrelated individuals, 120 in the homozygous state. The coding exons of ten expressed genes were found to be commonly deleted, including multiple genes with roles in sex steroid metabolism, olfaction and drug response. These common deletion polymorphisms typically represent ancestral mutations that are in linkage disequilibrium with nearby SNPs, meaning that their association to disease can often be evaluated in the course of SNP-based whole-genome association studies.     

Biological weapons

Anthrax has been a major cause of death in grazing animals and an occasional cause of death in humans for thousands of years. Since the late 1800s there has been an exceptional international history of anthrax vaccine development. Due to animal vaccinations, the rate of infection has dropped dramatically. Anthrax vaccines have progressed from uncharacterized whole-cell vaccines in 1881, to pXO2-negative spores in the 1930s, to culture filtrates absorbed to aluminum hydroxide in 1970, and likely to recombinant protective antigen in the near future. Each of these refinements has increased safety without significant loss of efficacy. The threat of genetically engineered, antibiotic and vaccine resistant strains of Bacillus anthracis is fueling hypothesis-driven research and global techniques--including genomics, proteomics and transposon site hybridization--to facilitate the discovery of novel vaccine targets. This review highlights historical achievements and new developments in anthrax vaccine research.