Multidrug resistance resulting from expression of an energy‐dependent drug efflux pump encoded by the human MDR1 gene is a major impediment to effective cancer therapy. Pharmacologic intervention aimed at inhibiting this multidrug transporter should improve existing chemotherapy of human cancer, but drug development has been delayed by the difficulty and expense of developing valid animal models. Using recombinant DNA technology, a transgenic mouse has been engineered whose bone marrow is protected from the toxic effects of chemotherapy by expression of the (...) MDR1 gene. This animal system allows the rapid screening of drugs which inhibit the multidrug transporter and heralds a new era of using transgenic animals for pharmacologic screening. (shrink)

In Respect for Nature Paul W. Taylor argues that there is a moral obligation to respect all living things. I argue that there is no such obligation. Taylor presents three basic premises for his position. The first two are shown to be mistaken but not necessary for Taylor's argument. The third, that being a nonsentient teleological centre of life confers moral significance, while necessary, fails to be rationally compelling. I argue: (1) The relevant concept of teleology as readily applies to (...) inanimate objects as it does to nonsentient life forms. (2) The inanimate–nonsentient distinction (at the relevant molecular level) is founded upon a continuum which offes no basis sufficient to justify The Life Principle. (3) The concept of teleology, as used by Taylor, is too unclear and ill-founded to serve as the basis for a rationally compelling argument. (shrink)

The Psalter exhibits a complex literary structure that not only determines its shape but also provides the reader with interpretive clues for reading both the whole and its parts.

Gewirth and hare claim amoralism is contrary to reason. Gewirth believes amoralism to be logically inconsistent. Hare believes amoralism to be imprudent and hence irrational. By defining the problem as one of amoralism rather than 'non'moralism, Gewirth and hare assume illegitimate moral presuppositions. I show their arguments fail by comparing their arguments to the arguments given by someone who accepts the language and presuppositions of magic. I suggest that what is wrong with amoralism is that it leads to immoralism. If (...) this is so, Morality ultimately must be based upon basic moral insights or intuitions. (shrink)

This study explores linkages between what Chinese managers generally know about environmental issues, how strongly they value environmental protection, and different types of behaviours/actions they may take within their organizations on behalf of the environment. From a sample of 305 managers in Guangzhou and Beijing, it was found that both environmental knowledge and values are more predictive of more personal managerial behaviours, such as keeping informed of relevant company issues and working within the system to minimize environmental impacts, than more (...) overt behaviours. Moreover, for these more personal actions, environmental knowledge and values were found to have both main and interactive effects. By comparison, it was found that both environmental values and knowledge had additive effects on managerial tendencies to initiate new programs within their domain of responsibility. Only environmental values was found to have a modest influence environmental advocacy. (shrink)

The mechanistic significance of a kinetic isotope effect on a cytochrome P‐450catalyzed reaction depends, fundamentally, on the nature of the interaction of the substrate with the active site of the enzyme as well as on the nature of the chemistry of the reaction catalyzed. Consequently, kinetic isotope effects can be used to extract information on the topology of the enzyme and the mechanism of substrate oxidation. Kinetic isotope effect studies are sometimes accompanied by ‘metabolic switching’ or a change in metabolic (...) pathway, catalyzed either by the same enzyme or by a different enzyme. For the specific case where ‘metabolic switching’ gives rise to a change in regional specificity for the cytochrome P‐450 catalyzed metabolism of a compound, this change can be explained in terms of the topological constraints on substrate binding imposed by the active site of the enzyme. (shrink)

A non-universal Immediate Dominance Condition on identity deletion is proposed to explain the systematic differences between languages like Chinese and languages like English in their respective patterns of coordination, topicalization, dislocation, and relativization. By assuming that this condition holds for languages of the Chinese-type, but not for those of the English-type, it is possible to account for the well-formed coordinations of all languages by means of a single universal principle of coordination reduction, and it is possible to derive the well-formed (...) topicalizations, dislocations, and relative clause constructions of all languages by means of the same set of universal principles of Copying, Deletion, and Pronominalization. (shrink)

The vertebrate retina is said to be inverted because the photoreceptors are oriented in the posterior direction and are thus unable to maximize photodetection under conditions of low illumination. The tapetum lucidum is a photoreflective structure located posterior to the photoreceptors in the eyes of some fish and terrestrial animals. The tapetum reflects light forward, giving incident photons a “second chance” to collide with a photoreceptor, substantially enhancing retinal photosensitivity in dim light. Across vertebrates (and arthropods), there are a wide (...) variety of tapeta that vary in structure, chemical composition, and even tissue architecture, indicating repeated convergent evolution. To date, the tapetum has not been observed in any cephalopod, however, which also possess a camera‐like eye, but with the retinal photoreceptors oriented in the anterior direction. We therefore hypothesize that the tapetum lucidum is a compensatory adaptation for the suboptimal design of the inverted retina of vertebrates. (shrink)

Mortal and immortal DNA : Craig Venter and the lure of "lamia" -- Homeopathy : Holmes, hogwarts, and the Prince of Wales -- Citizen Pinel and the madman at Bellevue -- The experimental pathology of stress : Hans Selye to Paris Hilton -- Gore's fever and Dante's Inferno : Chikungunya reaches Ravenna -- Giving things their proper names : Carl Linnaeus and W.H. Auden -- Spinal irritation and fibromyalgia : Lincoln's surgeon general and the three graces -- Tithonus and the (...) fruit fly : new science and old myths -- Swiftboating "America the beautiful" : Katharine Lee Bates and a Boston marriage -- Nothing makes sense in medicine except in the light of biology -- Apply directly to the forehead : Holmes, Zola, and Hennapecia -- Elizabeth Blackwell breaks the bonds -- Chronic lyme disease and medically unexplained syndromes -- Eugenics and the immigrant : Rosalyn Yalow and Rita Levi-Montalcini -- Science in the Middle East : Robert Koch and the cholera war -- How to win a Nobel prize : thinking inside and outside the box -- Homer Smith and the lungfish : the last gasp of intelligent design -- DDT is back : let us spray! -- Academic boycotts and the Royal Society -- Teach evolution, learn science : John William Draper and the "bone bill" -- Diderot and the yeti crab : the encyclopedias of life -- Dengue fever in Rio : Macumba versus Voltaire. (shrink)