Age of onset of drug use and its association with DSM-IV drug abuse and dependence: results from the National Longitudinal Alcohol Epidemiologic Survey

Although adaptive explanations for menstruation go back at least twenty-five hundred years, in the last decade two new hypotheses have been advanced. The first suggests that menstruation evolved to cleanse the uterus of pathogens introduced by sperm, and the second argues that the function of endometrial regression (with the associated menstruation in humans) is to save energy by getting rid of tissue, rather than maintaining it in the absence of an available blastocyst. Both these suggestions may be questioned on the grounds that they do not take into account the physiology of the reproductive processes involved. Menstruation is not an independent physiological process and is unlikely to have been selected for independently of the evolutionary events that led to it. Furthermore, most primitive menstruating animals would have menstruated infrequently, and many may have reproduced or died without ever menstruating. In order to provide a context for understanding how menstruation may have come about, the evolution of the female vertebrate reproductive tract is briefly reviewed. In later stages, the coevolution of the embryo and uterus resulted in an intimate association between the trophoblast and the uterine blood vessels. As the embryo became more invasive, the uterus responded with increased cellular growth and differentiation of the endometrium to accommodate it. This reached its peak in mammals (such as rodents and humans), where the embryo passes through the epithelium into the endometrial stroma, which responds with differentiation of cells and blood vessels. Progesterone, secreted after ovulation, plays a crucial role in preparation for pregnancy. In addition to its well-known effects on the uterus, progesterone may be important in suppressing the inflammatory reaction that would be expected in response to the presence of a foreign body, such as an embryo. It is also suggested that vascular and cellular differentiation of the endometrial stroma has evolved by adaptation of the inflammatory (granulation tissue) reaction. When progesterone levels fall at the end of the cycle, there is tissue breakdown and bleeding. The uterus then reforms for the next ovulatory cycle. It is shown that the female reproductive tract has multiple functions that must occur in sequence. The coevolution of the embryo and maternal tract thus led to the close contact of two genetically different tissues, and problems such as the inflammatory reaction had to be overcome. Menstruation is a necessary consequence of these evolutionary changes, and needed no adaptive value in order to evolve.     

The xenoestrogen bisphenol A induces growth, differentiation, and c-fos gene expression in the female reproductive tract

The xenoestrogen bisphenol A (BPA) has been shown to mimic estrogen both in vivo and in vitro. BPA stimulates PRL secretion and the expression of a PRL regulating factor from the posterior pituitary in the estrogen-sensitive Fischer 344 rat (F344), but not in Sprague-Dawley (SD) rats. The goal of the present studies was to examine the in vivo actions of BPA on the reproductive tract. The specific objectives were 1) to characterize the short term effects of BPA on cell proliferation and c-fos expression in the uterus and vagina, and 2) to compare the effects of prolonged exposure to low doses of BPA on the reproductive tract of F344 and SD rats. Treatment with single high doses of BPA induced cell proliferation in the uterus and vagina of ovariectomized F344 rats, as determined by bromodeoxyuridine immunostaining. This proliferation was dose dependent (from 37.5-150 mg/kg) and followed a time course similar to that of estradiol (E2). Quantitative RT-PCR revealed that both BPA and E2 increased c-fos messenger RNA levels in the uterus 14- to 16-fold within 2 h, which returned to basal levels after 6 h. In the vagina, BPA-induced c-fos expression remained elevated for up to 6 h, compared with the transient increase caused by E2. Treatment of F344 rats for 3 days with continuous release capsules that supplied a much lower dose of BPA (approximately 0.3 mg/kg x day) resulted in hypertrophy, hyperplasia, and mucus secretion in the uterus and hyperplasia and cornification of the vaginal epithelium. The reproductive tract of SD rats did not respond to this treatment paradigm with BPA. These studies demonstrate that 1) the molecular and morphological alterations induced by BPA in the uterus and vagina are nearly identical to those induced by estradiol; 2) the vagina appears to be especially sensitive to the estrogenic actions of BPA; 3) the reproductive tract of the inbred F344 rat appears more sensitive to BPA than that of the outbred SD rat; and 4) continuous exposure to microgram levels of BPA is sufficient for exerting estrogenic actions.     

Effect of exercise on the plasma nonesterified fatty acid composition of dogs and goats: Species with different aerobic capacities and diets

The goals of this study were to determine: (i) whether mammals mobilize particular nonesterified fatty acids (NEFA) preferentially during locomotion, (ii) if differences in aerobic capacity or diet can affect the pattern of NEFA mobilization and (iii) which individual NEFA are most representative of total NEFA concentration changes, to use them as tracers for turnover studies. Individual NEFA were measured in trained dogs and goats (VO₂max dog/VO₂max goat=2.2; where VO₂max=max-imal oxygen consumption) during treadmill exercise at 40 and 60% VO₂max. Important interspecies differences in individual NEFA concentrations could be attributed to differences in aerobic capacity. The more aerobic species (dog) had much higher plasma NEFA concentrations for all but one NEFA (18∶0), when compared with the low-aerobic species (goat). In addition, exercise caused a large increase in concentration of individual NEFA in the dogs, with the largest increases seen in 18∶1 (150% above resting values) and 16∶0 (60% increase), but it had no effect in goats. Therefore, the aerobic species has a much higher ability for mobilizing and transporting NEFA in plasma than its low-aerobic counterpart. Two NEFA accounted for more than half total plasma NEFA in both species, 18∶1 (about 35% total NEFA) and 16∶0 (20%). Calculation of variability in percent composition reveals that oleate and palmitate also closely reflect changes in total NEFA and are therefore the most appropriate tracers forin vivo kinetic studies in exercising mammals. Differences in diet and digestion physiology explained some differences in the plasma NEFA composition of the two species; this was reflected in the percent contributions of individual fatty acids to total NEFA: in dogs 18∶1>16∶0>18∶2>18∶0, while in goats 18∶1>16∶0>18∶0>18∶2. Also, only goats had 18∶3 (6% total NEFA), a fatty acid of plant origin, while only dogs had 16∶1 (7% total NEFA). Overall, however, the plasma NEFA composition of goats did not exactly reflect that of their diet due to preabsorptive modification of unsaturated fatty acids, while in dogs there was a good correlation between dietary and plasma NEFA.     

Induction of forward mutations at the thymidine kinase locus of mouse lymphoma cells: evidence for electrophilic and non-electrophilic mechanisms

A database of 209 chemicals tested for induction of forward mutations at the heterozygous thymidine kinase (TK +/-) locus in L5178Y mouse lymphoma cells was analyzed for structure-activity relationships using the MultiCASE expert system. Consistent with evidence of several contributing biological mechanisms, these studies suggest that such mutations may occur by more than one mechanism. As might be expected, there was evidence for a component involving direct electrophilic attack on the cellular DNA, in a manner previously established as causative in the induction of mutations in Salmonella. In addition, however, there was also strong evidence for another mechanism or mechanisms involving chromosome missegregation, cellular toxicity or an alternate site of action, such as the microtubules.     

Reasoning in inconsistent knowledge bases

Databases and knowledge bases could be inconsistent in many ways. For example, during the construction of an expert system, we may consult many different experts. Each expert may provide us with a group of rules and facts which are self-consistent. However, when we coalesce the facts and rules provided by these different experts, inconsistency may arise. Alternatively, knowledge bases may be inconsistent due to the presence of some erroneous information. Thus, a framework for reasoning about knowledge bases that contain inconsistent information is necessary. However, existing frameworks for reasoning with inconsistency do not support reasoning by cases and reasoning with the law of excluded middle (“everything is either true or false”). In this paper, we show how reasoning with cases, and reasoning with the law of excluded middle may be captured. We develop a declarative and operational semantics for knowledge bases that are possibly inconsistent. We compare and contrast our work with work on explicit and non-monotonic modes of negation in logic programs and suggest under what circumstances one framework may be preferred over another     

Fibronectin fragments modulate human retinal capillary cell proliferation and migration

Capillary morphogenesis involves cell-cell and cell-matrix interactions. Proteases elaborated by capillary cells modify the extracellular matrix (ECM) to facilitate capillary tube formation. Previously, we detected the presence of fibronectin fragments (Fn-f) associated with the proform of matrix metalloprotease-2 (MMP-2) in conditioned medium of human retinal endothelial cells (HRECs). Association of this fragment to latent MMP-2 prevented autocatalytic activation of MMP-2, suggesting a modulatory role of Fn-f in MMP-2 activation. In this report, we examined the potential role of Fn-f on two processes involved in angiogenesis, proliferation and migration of vascular cells. The effects of Fn-f on proliferation were determined by DNA synthesis and cell counts. Their effects on migration were assessed using modified Boyden chambers. Seven Fn-f were tested on vascular cell migration and/or proliferation. Three Fn-f induced migration. Fn-f of 30-kDa and 120-kDa size positively affected proliferation of microvascular cells but not macrovascular cells. A 45-kDa gelatin binding fragment of Fn inhibited HREC proliferation but stimulated pericyte and smooth muscle cell proliferation. The potency of these fragments exceeded that of the known angiogenic growth factor, basic fibroblast growth factor (bFGF), on HREC migration. ECM components such as fibronectin may influence capillary morphogenesis by the generation of fragments that can modulate proliferation, migration, and protease activation. In the setting of diabetes, excess Fn is generated and is available for degradation. Thus, the production of Fn-f may be specifically relevant to the angiogenesis observed in proliferative diabetic retinopathy.     

Report on a new OED project: A study of the history of new words in the new OED

The study of the history of new words in theNewOED described in this paper was undertaken in 1986-87, and is based on the material then available. Since then, theNewOED has been finished, and PAT, the inquiry system developed at the University of Waterloo for the investigation of theNewOED data base, has been much altered and improved. Nevertheless, this report should prove useful in indicating the potentiality for analyzing the computerizedNewOED and some of the problems. This project is a study of the ways in which new words are created in English at various periods of time. A chronological dictionary 's created listing words introduced into the language over 50 year increments. These words are then classified by the processes used in forming them to show, in proportional terms, if certain processes are more common at some times than at others.H. M. Logan, Associate Professor, Department of English, University of Waterloo, Waterloo, Ontario, Canada, has written The Dialect of the Middle English Life of St. Katherine (Mouton, 1973), making use of the computer in a study of medieval dialectology. He has also written articles on computer stylistics and literary analysis inCHum, ALLC Journal, Language and Style, College Literature, and on the dictionary inDictionaries.     

Overview of Tiber-II—Evolution toward an Engineering Test Reactor

TIBER II is designed to be a minimum size and cost candidate for an international Engineering Test Reactor. High-current density Nb₃Sn superconducting magnets with radiation-tolerant polymide insulation is combined with a minimum thickness tungsten inbored shield and a common, external vacuum boundary to minimize the inner radial build of the tokamak core. This results in a major radius of 3 m, compared to 5 m for previous ETR designs such as INTOR, with correspondingly lower costs expected. Cyclic stress fatigue limits the number of pulses so that steady-state current drive, based on a combination of neutral beams, lower hybrid and ECH, is designed to achieve reactor-relevant nuclear testing conditions (Fluence 3MW yr/m², rwall > 1 MW/m² in steady state).This report is abstracted from a more complete information document UCID-20863 with numerous authors. See Ref. l for complete credits.     

Analysis and tuning of adaptive generalized predictive control

The adaptive Generalized Predictive Controller (Clarke et al., 1987a, b) is capable of controlling plants with variable dead-time, unknown model orders and unstable poles and zeros. This paper shows how the GPC control law can be written in an equivalent general linear transfer function form which simplifies closed-loop (eg. root locus) analysis. Three recommended strategies for selecting the design parameters during the commissioning stage allow the user to adjust the closed-loop speed of response on-line using only a single active tuning parameter. Experimental runs confirm the ability of adaptive GPC to provide a consistent closed-loop response in spite of large process changes.