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)

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.

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)

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)

Despite the burgeoning literature on professionalism in other health professions, psychology lags behind in the level of attention given to this core competency. In this article, we review definitions from other health professions and how they address professionalism. Next, we review how this competency evolved within health service psychology (HSP), and we propose a definition. We offer an approach for assessing professionalism within HSP. Consideration is given to strategies and methods for providing effective education and training in this multifaceted competency. (...) Finally, recommendations are made for creating a culture of professionalism within HSP and honoring psychology’s social contract with multiple publics. (shrink)

Foundation models such as GPT-4 are fine-tuned to avoid unsafe or otherwise problematic behavior, such as helping to commit crimes or producing racist text. One approach to fine-tuning, called reinforcement learning from human feedback, learns from humans' expressed preferences over multiple outputs. Another approach is constitutional AI, in which the input from humans is a list of high-level principles. But how do we deal with potentially diverging input from humans? How can we aggregate the input into consistent data about "collective" (...) preferences or otherwise use it to make collective choices about model behavior? In this paper, we argue that the field of social choice is well positioned to address these questions, and we discuss ways forward for this agenda, drawing on discussions in a recent workshop on Social Choice for AI Ethics and Safety held in Berkeley, CA, USA in December 2023. (shrink)

This article begins with a review of studies in perception and depth psychology concerning the experience of exposure to sacred artworks in Roman Catholic and Eastern Orthodox contexts. This follows with the results of a qualitative inquiry involving 45 Roman Catholic, Eastern and Coptic Orthodox, and Protestant Christians in Canada. First, participants composed narratives detailing memories of spiritual experiences involving iconography. Then, in the context of a darkened room evocative of a sacred space, they viewed artworks depicting Biblical themes and (...) interpreted their meanings. Stimuli included “Western” paintings from the Roman tradition—a selection from the Gothic, Northern Renaissance, and Renaissance canon—and matched “Eastern” icons in the Byzantine style. Spiritual experience narratives were analyzed in terms of word frequencies, and interpretations of sacred artworks were analyzed thematically. Catholics tended to utilize emotional language when recalling their spiritual experiences, while religious activity was most often the concern of Protestants, and Orthodox Christians wrote most about spiritual figures and their signifiers. A taxonomy of response styles was developed to account for participants’ interpretations of Western and Eastern artworks, with content ranging from detached descriptions to projective engagement with the art-objects. Our approach allows for representation of diverse Christians’ interpretations of sacred art, taking into consideration personal, collective, and cultural-religious sources of meaning. Our paradigm also offers to enrich our understanding of the numinous or emotional dimension of mystical contact. (shrink)

This afterword extends and refines the arguments presented in Cohen and Jacobs . The main point made by the authors is that the antidepressant randomized controlled trial world is a make-believe world in which researchers act as if a bona fide medical experiment is being conducted. From the assumed existence of the “disorder” and the assumed homogeneity of the treatment groups, through the validity of rating scales and the meaning of their scores, to the presentations of researchers’ ratings as (...) the genuine outcome of interest — all aspects of such trials are make-believe. The continued acceptance of randomized controlled trials as appropriate mechanisms to ascertain the actual effects of psychoactive drugs on human beings in distress confirms that researchers are inextricably dependent on large-scale organizational and financial interests that require the sustained production of make-believe results about psychoactive drugs. (shrink)

[1] Hagadah shel Pesaḥ -- [2] Pirḳe Avot -- [3] Mishle -- [4] Shir ha-shirim -- [5] Megilat Ḳohelet -- 6. Megilat Ekhah -- [7] Megilat Rut -- [8] Sefer Tehilim.

How do Dutch people let each other know that they disagree? What do they say when they want to resolve their difference of opinion by way of an argumentative discussion? In what way do they convey that they are convinced by each other’s argumentation? How do they criticize each other’s argumentative moves? Which words and expressions do they use in these endeavors? By answering these questions this short essay provides a brief inventory of the language of argumentation in Dutch.

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)