The heme‐containing cytochromes P‐450 are a ubiquitous family of monooxygenase isozymes responsible for the oxidative metabolism of a wide variety of endogenous as well as exogenous compounds. Many of the compounds metabolized by this enzyme system are effectively detoxified and converted to derivatives more easily eliminated from the organism. However, some compounds can be activated to reactive species capable of eliciting a cascade of toxic lesions, including cancer. Since its discovery nearly 30 years ago, the cytochrome P‐450 enzyme system has (...) received a great deal of attention, particularly in the areas of their mechanisms of metabolism, range of substrate specificity, the purification and characterization of the multiple isozymes and, more recently, the regulation of expression of specific forms. This review will discuss current notions concerning the expression of at least one cytochrome P‐450 isozyme and future directions that should lead to a more complete understanding of cytochrome P‐450 gene expression in general, particularly as it impacts upon biochemical pharmacology. (shrink)

Thought experiments analogous to those discussed by Landau and Peierls are studied in the framework of a manifestly covariant relativistic quantum theory. It is shown that momentum and energy can be arbitrarily well defined, and that the drifts induced by measurement in the positions and times of occurrence of events remain within the (stable) spread of the wave packet in space-time. The structure of the Newton-Wigner position operator is studied in this framework, and it is shown that an analogous time (...) operator can be constructed which satisfies the canonical commutation relation with the energy E but does not commute (due to the presence of a time drift term) with the momentum p. The resulting commutation relation is used as a mathematical basis for the derivation of the Landau-Peierls relation Δt Δp≳ħ/c. (shrink)

Continuous recordings of brain electrical activity were obtained from a group of 176 patients throughout surgical procedures using general anesthesia. Artifact-free data from the 19 electrodes of the International 10/20 System were subjected to quantitative analysis of the electroencephalogram (QEEG). Induction was variously accomplished with etomidate, propofol or thiopental. Anesthesia was maintained throughout the procedures by isoflurane, desflurane or sevoflurane (N = 68), total intravenous anesthesia using propofol (N = 49), or nitrous oxide plus narcotics (N = 59). A set (...) of QEEG measures were found which reversibly displayed high heterogeneity of variance between four states as follows: (1) during induction; (2) just after loss of consciousness (LOC); (3) just before return of consciousness (ROC); (4) just after ROC. Homogeneity of variance across all agents within states was found. Topographic statistical probability images were compared between states. At LOC, power increased in all frequency bands in the power spectrum with the exception of a decrease in gamma activity, and there was a marked anteriorization of power. Additionally, a significant change occurred in hemispheric relationships, with prefrontal and frontal regions of each hemisphere becoming more closely coupled, and anterior and posterior regions on each hemisphere, as well as homologous regions between the two hemispheres, uncoupling. All of these changes reversed upon ROC. Variable resolution electromagnetic tomography (VARETA) was performed to localize salient features of power anteriorization in three dimensions. A common set of neuroanatomical regions appeared to be the locus of the most probable generators of the observed EEG changes. (shrink)

In many animal species, the early development of the embryo follows a stereotypic pattern of cell cleavage, lineage allocation and generation of tissue asymmetry leading to delineation of the body plan with three primary embryonic axes. The mammalian embryo has been regarded as an exception and primary body axes of the mouse embryo were thought to develop after implantation. However, recent findings have challenged this view. Asymmetry in the fertilised oocyte, as defined by the position of the second polar body (...) and the sperm entry point, can be correlated with the orientation of the animal–vegetal and the embryonic–abembryonic axes in the preimplantation blastocyst. Studies of the pattern of morphogenetic movement of cells and genetic activity in the peri‐implantation embryo suggest that the animal–vegetal axis of the blastocyst might presage the orientation of the anterior–posterior axis of the gastrula. This suggests that the asymmetry of the zygote that is established at fertilisation and early cleavage has a lasting impact on the delineation of body axes during embryogenesis. BioEssays 23:508–517, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

The dynamical equations of relativistic quantum mechanics prescribe the motion of wave packets for sets of events which trace out the world lines of the interacting particles. Electromagnetic theory suggests thatparticle world line densities be constructed from concatenation of event wave packets. These sequences are realized in terms of conserved probability currents. We show that these conserved currents provide a consistent particle and antiparticle interpretation for the asymptotic states in scattering processes. The relation between current conservation and unitarity is used (...) to establish relations between pair production and annihilation amplitudes and scattering. The discrete symmetriesC, T, P are studied and it is shown that no Dirac sea (for fermions where such a construction is possible, or bosons where it is not) is required for consistency of the theory. These currents, furthermore, represent the discrete symmetries in a way consistent with their interpretation as particle currents. (shrink)

Background: Nursing students on clinical placements as part of their professional training are routinely faced with situations involving ethical conflicts. The initial act of perceiving a situation as causing an ethical dilemma is the result of both the students’ personal values, drawn from their culture and families, and of the professional knowledge and values that they have acquired through training and experience. Objectives: Nursing students’ experiences on clinical placements in primary care settings were investigated in order to identify situations that (...) they perceived as involving ethical conflict and describe the elements they took into consideration during their decision-making processes in these situations. Methods: The research design was qualitative descriptive case study. Around 50 students from three different intakes to a nursing degree answered a questionnaire and discussed it in focus groups. Ethical considerations: The study was designed in accordance with the principles guiding research with human beings and was approved by the Human Research Ethics Committee. Results: Synthesised into two principal axes: (a) ethical conflicts in primary care, linked with the domains of working processes, professional nursing ethics and human and social rights and (b) students’ decision-making processes – realisation, reflection and intervention. Conclusion: The student nurses saw themselves both as actors and spectators in situations involving ethical problems and demanding moral deliberation, demonstrating the ability to base their arguments soundly. They tended to emphasise the possibilities offered by dialogue and that different ethical values must be respected to find fair solutions to ethical problems. (shrink)

BackgroundLarge-scale, centralized data repositories are playing a critical and unprecedented role in fostering innovative health research, leading to new opportunities as well as dilemmas for the medical sciences. Uncovering the reasons as to why citizens do or do not contribute to such repositories, for example, to population-based biobanks, is therefore crucial. We investigated and compared the views of existing participants and non-participants on contributing to large-scale, centralized health research data repositories with those of ex-participants regarding the decision to end their (...) participation. This comparison could yield new insights into motives of participation and non-participation, in particular the behavioural change of withdrawal.MethodsWe conducted 36 in-depth interviews with ex-participants, participants, and non-participants of a three-generation, population-based biobank in the Netherlands. The interviews focused on the respondents’ decision-making processes relating to their participation in a large-scale, centralized repository for health research data.ResultsThe decision of participants and non-participants to contribute to the biobank was motivated by a desire to help others. Whereas participants perceived only benefits relating to their participation and were unconcerned about potential risks, non-participants and ex-participants raised concerns about the threat of large-scale, centralized public data repositories and public institutes, such as social exclusion or commercialization. Our analysis of ex-participants’ perceptions suggests that intrapersonal characteristics, such as levels of trust in society, participation conceived as a social norm, and basic societal values account for differences between participants and non-participants.ConclusionsOur findings indicate the fluidity of motives centring on helping others in decisions to participate in large-scale, centralized health research data repositories. Efforts to improve participation should focus on enhancing the trustworthiness of such data repositories and developing layered strategies for communication with participants and with the public. Accordingly, personalized approaches for recruiting participants and transmitting information along with appropriate regulatory frameworks are required, which have important implications for current data management and informed consent procedures. (shrink)

The current article aims to provide an up-to-date synopsis of available techniques to study affect dynamics using intensive longitudinal data (ILD). We do so by introducing the following eight dichotomies that help elucidate what kind of data one has, what process aspects are of interest, and what research questions are being considered: (1) single- versus multiple-person data; (2) univariate versus multivariate models; (3) stationary versus nonstationary models; (4) linear versus nonlinear models; (5) discrete time versus continuous time models; (6) discrete (...) versus continuous variables; (7) time versus frequency domain; and (8) modeling the process versus computing descriptives. In addition, we discuss what we believe to be the most urging future challenges regarding the modeling of affect dynamics. (shrink)

RésuméL'objet du présent article est de dégager la signification philosophique des différents théoriémes de métamathématique relatifs à la puissance des formalisations. Ces théorèmes représentent la partie de l'épistémologie qui peut être exposée dans la forme technique de la science elle‐même et rassemblant les éléments d'une réflexion autocritique de la pensée mathématique sur elle‐même. Au‐delà, ils invitent à comprendre l'acte de la pensée mathématique comme déploiement d'un projet pensant supposant à la fois une initiative volontaire de la pensée, un champ intuitif (...) absolument indéfini et une exigence logique régulatrice, et amènent la philosophie de la science à se demander si, telles qu'ellcs sont, les mathématiques sont l'unique forme de synthèse rigoureuse possible entre ces trois moments de la pensée. (shrink)

In this extremely well-written study, the author interprets man as striving towards the fullness of his personal freedom, which is achieved in the love of God. Werner's intimate familiarity with the history of philosophy and his awareness of the findings of biology and psycho-analysis enable him to develop his theme with rigor and depth. --R. P. I.

Consider the concept combination ‘pet human’. In word association experiments, human subjects produce the associate ‘slave’ in relation to this combination. The striking aspect of this associate is that it is not produced as an associate of ‘pet’, or ‘human’ in isolation. In other words, the associate ‘slave’ seems to be emergent. Such emergent associations sometimes have a creative character and cognitive science is largely silent about how we produce them. Departing from a dimensional model of human conceptual space, this (...) article will explore concept combinations, and will argue that emergent associations are a result of abductive reasoning within conceptual space, that is, below the symbolic level of cognition. A tensor-based approach is used to model concept combinations allowing such combinations to be formalized as interacting quantum systems. Free association norm data is used to motivate the underlying basis of the conceptual space. It is shown by analogy how some concept combinations may behave like quantum-entangled particles. Two methods of analysis were presented for empirically validating the presence of non-separable concept combinations in human cognition. One method is based on quantum theory and another based on comparing a joint probability distribution with another distribution based on a separability assumption using a chi-square goodness-of-fit test. Although these methods were inconclusive in relation to an empirical study of bi-ambiguous concept combinations, avenues for further refinement of these methods are identified. (shrink)