Showing papers by "University of Toronto published in 1976"
TL;DR: Observations on the molecular basis of pleiotropic drug resistance are interpreted in terms of a model wherein certain surface glycoproteins control drug permeation by modulating the properties of hydrophobic membrane regions.
3,243 citations
TL;DR: The Internal Model Principle is extended to weakly nonlinear systems subjected to step disturbances and reference signals and is shown that, in the frequency domain, the purpose of the internal model is to supply closed loop transmission zeros which cancel the unstable poles of the disturbance andreference signals.
2,613 citations
TL;DR: It is reported here that all clinically effective antipsychotic drugs (tested so far) block the stereo-specific binding of 3H-haloperidol at concentrations which correlate directly with the clinical potencies.
Abstract: ANTIPSYCHOTIC drugs, or neuroleptics, are thought to act by blocking dopamine receptors in the nervous system1–4. Recent direct evidence, based on stereospecific binding assays, supports this hypothesis of antipsychotic drug action5–9. As only a few antipsychotic drugs had been tested for their effects on the binding of haloperidol5–8, the question remained whether all antipsychotic drugs, regardless of chemical structure, would block the stereospecific binding of haloperidol. We report here that all clinically effective antipsychotic drugs (tested so far) block the stereo-specific binding of 3H-haloperidol at concentrations which correlate directly with the clinical potencies.
1,587 citations
TL;DR: In this paper, it was shown that there is a robust controller for a linear, time-invariant, multivariable system (plant) that asymptotic tracking/regulation occurs independent of input disturbances and arbitrary perturbations in the plant parameters of the system.
Abstract: Necessary and sufficient conditions are found for there to exist a robust controller for a linear, time-invariant, multivariable system (plant) so that asymptotic tracking/regulation occurs independent of input disturbances and arbitrary perturbations in the plant parameters of the system. In this problem, the class of plant parameter perturbations allowed is quite large; in particular, any perturbations in the plant data are allowed as long as the resultant closed-loop system remains stable. A complete characterization of all such robust controllers is made. It is shown that any robust controller must consist of two devices 1) a servocompensator and 2) a stabilizing compensator. The servocompensator is a feedback compensator with error input consisting of a number of unstable subsystems (equal to the number of outputs to be regulated) with identical dynamics which depend on the disturbances and reference inputs to the system. The sorvocompensator is a compensator in its own right, quite distinct from an observer and corresponds to a generalization of the integral controller of classical control theory. The sole purpose of the stabilizing compensator is to stabilize the resultant system obtained by applying the servocompensator to the plant. It is shown that there exists a robust controller for "almost all" systems provided that the number of independent plant inputs is not less than the number of independent plant outputs to be regulated, and that the outputs to be regulated are contained in the measurable outputs of the system; if either of these two conditions is not satisfied, there exists no robust controller for the system.
1,199 citations
937 citations
TL;DR: It is not known what the critical property (or properties) is that makes initiated cells so important in carcinogens and the failure to understand and manipulate this early step has been a major impediment to its analysis.
Abstract: THE development of cancer following exposure to chemical carcinogens or to various forms of irradiation is almost invariably slow and prolonged. Although the process can be initiated by a brief exposure to a carcinogenic stimulus, there is no evidence that target cells so altered are cancer cells. Rather, there is abundant indirect evidence from many systems that what is induced is an altered cell or cell population from which malignant neoplasia can gradually develop or evolve1,2. Neoplastic development therefore resembles a chain reaction, triggered by exposure to a carcinogen, in which the links are new populations with altered organisational, structural and biochemical properties. These slowly proliferative new lesions are characteristically focal in distribution, implying that only a small proportion of the original target cell population in any organ or tissue participates. It is not known what the critical property (or properties) is that makes initiated cells so important in carcinogens and the failure to understand and manipulate this early step has been a major impediment to its analysis.
825 citations
TL;DR: Electroacupuncture in awake mice produced analgesia to noxious heat stimuli causing a 54% increase in latency to squeak, implying that endorphin is released at a low basal rate in “normal” mice, and at a much higher rate during acupuncture.
583 citations
459 citations
TL;DR: An effective procedure for performing a relational scheme synthesis is presented and the schema that results from this procedure is proved to be in Codd's third normal form and to contain the fewest possible number of relations.
Abstract: It has been proposed that the description of a relational database can be formulated as a set of functional relationships among database attributes. These functional relationships can then be used to synthesize algorithmically a relational scheme. It is the purpose of this paper to present an effective procedure for performing such a synthesis. The schema that results from this procedure is proved to be in Codd's third normal form and to contain the fewest possible number of relations. Problems with earlier attempts to construct such a procedure are also discussed.
450 citations
TL;DR: The aluminium content of 585 areas sampled in 10 post-mortem cases of Alzheimer's disease ranging in age from 50 to 88 years, in which the diagnosis was based on the specific histological appearances, revealed an elevated aluminium content in some regions.
Abstract: Aluminium is neurotoxic and results in the proliferation of 100 A diameter filaments in the cytoplasm of certain neurons. The aluminium concentration for 7 normal human brains was 1-9 +/- 0-7 SD mug/g dry weight (n = 208 samples). The aluminium content of 585 areas sampled in 10 post-mortem cases of Alzheimer's disease ranging in age from 50 to 88 years, in which the diagnosis was based on the specific histological appearances, revealed an elevated aluminium content in some regions. A range of 0-4 - 107-0 mug/g was encountered and 28 per cent of all regions sampled had concentrations in excess of 4 mug/g. Five of 6 cerebral biopsies from patients with Alzheimer's disease also had elevated aluminium content. In 2 additional Alzheimer's brains with neurofibrillary degeneration restricted to certain anatomical areas, elevated aluminium content was found to be associated with neurofibrillary degeneration and not with senile plaques. Furthermore, elevated aluminium content in multiple cortical regions was not found in 2 vascular dementias of the elderly. While the cytotoxic concentration for human neurons is unknown, the cytotoxic concentration for cat's cerebral neurons appears to lie between 4 and 6 mug/g dry weight.
435 citations
TL;DR: A strong case is made for the study of distributional properties of reaction time data by showing how some current theories of recognition memory are inadequate or wrong when examined in the light of distributiona l analyses.
Abstract: A method of analyzing reaction time data in recognition memory is presented, which uses an explicit model of latency distributions. This distributional method allows us to distinguish between processes in a way that the traditional measure, mean latency, can not. The behavior of latency distributions is described, and four experiments are reported that show how recognition accuracy and latency vary with independent variables such as study and test position, rate of presentation, and list length. These data are used to develop and test the empirical model. The resulting analyses, together with functional relationships derived from the experimental data, are used to test several theories of recognition memory. The theories examined all show problems in light of these stringent tests, and general properties required by a model to account for the data are suggested. As well as arguing for distributional analyses of reaction time data, this paper presents a wide range of phenomena that any theory of recognition memory must explain. Over the last few years, researchers have been developing theories of recognition memory based not only on accuracy measures but also on latency measures. In this article, we consider latency measures in recognition memory. Results from four experiments are presented, and an empirical model for latency distributions is developed. Latency distributions are shown to provide much more information than can be obtained from mean latency, the most common dependent variable in reaction time measurements. From this, a strong case is made for the study of distributional properties by showing how some current theories are inadequate or wrong when examined in the light of distributiona l analyses. These recent theories are further evaluated using functional relationships extracted from results of the four experiments presented.
TL;DR: The only finding reminiscent of perceptual “saccadic suppression” and mislocation effects is that a target which steps to a position ahead of a saccade is sometimes ignored.
TL;DR: In a flashed target variation of the Wheeless paradigm, “cancellation time” is not observed in circumstances where the first target is believed to be ineffective, and latency is approximately the same whether target steps are synchronized to saccades or not.
TL;DR: A method for the clonal analysis of murine erythroleukemia cells has been developed which allows the precise characterization of the number of progeny produced by each cell and the degree of differentiation of each progeny cell, and it is observed that the commitment decision limits the subsequent proliferative capacity of the cell to four additional cell divisions.
TL;DR: Evidence for GABA as a transmitter and effects of GABA on muscle fiber membrane receptors, andexcitatory transmitter substances 5.1.5.3.
TL;DR: TREHUB et al. as mentioned in this paper found that infants 5-17 weeks of age were presented with foreign speech sounds which were contingent upon their nonutritive sucking and when the infants met a specified criterion of sucking decrement, a contrasting sound was substituted.
Abstract: TREHUB, SANDRA E. The Discrimination of Foreign Speech Contrasts by Infants and Adults. CHILD DEVELOPMENT, 1976, 47, 466-472. Infants 5-17 weeks of age were presented with foreign speech sounds which were contingent upon their nonutritive sucking. When the infants met a specified criterion of sucking decrement, a contrasting sound was substituted. Significant differences in response recovery for experimental versus control (no sound change) subjects were found for the contrast pairs [pa]-[p-a] and [za]-[ia]. Adults were presented with a comparable discrimination task for the foreign contrasts [za]-[ia] and the English contrasts [li]-[ri]. It was found that adults achieved perfect accuracy with English contrasts but readily confused the foreign contrasts. The implications of these results for theories of perceptual development are discussed.
TL;DR: During blue-green algal blooms, other algae can be completely suppressed, and iron deprivation induces the production of hydroxamate chelators, which appear to be the agent suppressing other algae.
Abstract: During blue-green algal blooms, other algae can be completely suppressed. This ability of blue-green algae to suppress other algae may be determined by the abailability of iron. Iron deprivation induces the production of hydroxamate chelators, which appear to be the agent suppressing other algae.
TL;DR: In this article, the direction of a secondary magnetization component is found from the intersection point of converging remagnetization circles using a method based on the least-squares fitting of great circles to points on a sphere.
Abstract: Summary The direction of a secondary magnetization component is found from the intersection point of converging remagnetization circles using a method based on the least-squares fitting of great circles to points on a sphere. The technique may be applied to any problem that requires the best intersection point of convergent great circles and is thus useful in other fields besides palaeomagnetism, such as structural geology, plate tectonics and astronomy.
TL;DR: The ages at which the maxillary and mandibular teeth of 121 boys and 111 girls reached 14 mineralization stages were determined from serial cephalograms at the Burlington Growth Centre, more comprehensive than any previously available.
Abstract: The ages at which the maxillary and mandibular teeth of 121 boys and 111 girls reached 14 mineralization stages were determined from serial cephalograms at the Burlington Growth Centre. The present data are more comprehensive than any previously available and can be applied to chronological age determinations in juveniles of indefinite age, and of specimens in anthropological and forensic investigations. The sexes differed in the age at which they attained the stages of mineralization, with the canines demonstrating the greatest difference. In each sex, the ages at identical stages were similar for the corresponding teeth in the maxilla and mandible. Variability in age was greater among the males, especially for the first premolars, and increased with age, except for the third molars. Variability in age of third molar mineralization was greater in females and diminished among both sexes at late stages of root formation.
TL;DR: In this article, the wavelength dependence of interstellar linear polarization [p(λ) was investigated using the usual Serkowski relation with three parameters: p max, λ max, and K. Optical and infrared measurements were obtained simultaneously in eight photometric passbands between U and K, giving a coherent data set for a total of 105 reddened stars.
Abstract: New observations of the wavelength dependence of interstellar linear polarization [p(λ)] made to investigate the influence of the environment on the effective size distribution of the aligned polarizing particles are presented. Optical and infrared measurements were obtained simultaneously in eight photometric passbands between U and K, giving a coherent data set for a total of 105 reddened stars. The p(λ) data were modeled using the usual Serkowski relation with three parameters: p max , λ max , and K
TL;DR: No intermediaries were found between two discriminably different colors: rather, one changed abruptly to the other, and the abrupt change of color occurred even when the stimuli were doubly disparate, in shape and color.
TL;DR: Three mechanisms for resistance to methotrexate (Mtx) have been identified in Chinese hamster ovary cells selected for Resistance to this drug and all three classes of resistant cells retain their Mix-resistant phenotype when cultured under nonselectivve conditions.
Abstract: Three mechanisms for resistance to methotrexate (Mtx) have been identified in Chinese hamster ovary (CHO) cells selected from resistance to this drug. First-step selections produce cells with either an apparent structural alteration in the enzyme dihydrofolate reductase (class I), or a decreased permeability to the drug (class II). Mutagenesis with ethyl methanesulfonate increases the proportion of Mtx-resistant cells 5-10-fold. Second-step selections to higher resistance using class I resistant cells as parents results in cells with an increased activity of the reductase enzyme (class III) with no apparent further qualitative alterations in the enzyme. All three classes of resistant cells retain their Mtx-resistant phenotype when cultured under nonselectivve conditions.
TL;DR: The authors' findings indicate a significant nociceptive input to V main sensory-oralis neurones, a proportion of which relay directly to the ventrobasal thalamus and may be involved in perceptual and reflex aspects of responses to noxious and innocuous V stimuli.
TL;DR: Since the late 1950's, many experimental studies in which phytoseiid mites were artificially introduced have been conducted, both in controlled environments, such as glasshouses, and in the field, where the overall impact of the predators on their prey populations was demonstrated, but they did not reveal the actual mechanisms of the controlling processes.
Abstract: Predacious mites of the family Phytoseiidae form a diverse group that occurs throughout the world. They have been recognized as one of the most valuable groups of predators of tetranychid mites since the beginning of this century (CHANT, 1959). Since the late 1950's, many experimental studies in which phytoseiid mites were artificially introduced have been conducted, both in controlled environments, such as glasshouses, and in the field. More precise studies on the interactions between natural populations of phytoseiids and their prey mites also have been conducted (see reviews by HUFFAKER et al., 1969, HUFFAKER et al., 1970, and McMURTRY et al., 1970). In some of these studies (e. g. HUFFAKER and KENNETT, 1953, 1956; COLLYER, 1958, 1964; CHANT, 1961a; BRAVENBOER and DOSSE, 1962; LAING and HUFFAKER, 1969; FLAHERTY and HoY, 1971) the effects of the predators on their prey populations were profound, but in others (e.g. ANDERSON and MORGAN, 1958; CHANT, 1959) certain species of phytoseiids were of little value in the control of tetranychid mites. In addition, the effectiveness of a certain species of phytoseiid was shown to vary depending on a number of environmental factors (CHANT and FL~SCHNER, 1960). Nevertheless, most of these studies demonstrated only the overall impact of the predators on their prey populations, and they did not reveal the actual mechanisms of the controlling processes. There are several difficulties involved in studies of the interactions between phytoseiid mites and their prey. Firstly, because of the small sizes of the animals (only 300 to 600/~, and 400 to 900/~ in body length of the adult females of phytoseiid and tetranychid mites, respectively), accurate population censuses are often difficult. Secondly, because their generations overlap and mortality in the prey populations, including mortality caused by predation, cannot be assessed practically, approaches such as life table analyses or key factor analyses are not feasible. Thus, simple population studies of these mites alone Obviously have limited value for determining
TL;DR: The identity of some of the compounds produced as well as their relative phytotoxicity to lettuce seed and seedlings were determined by using paper, thin-layer, and gas chromatography as mentioned in this paper.
Abstract: Residues from corn and rye plants were allowed to decompose in soil for periods up to 30 days at 22–23 °C, and the identity of some of the compounds produced as well as their relative phytotoxicity to lettuce seed and seedlings were determined. Paper, thin-layer, and gas chromatography were the principal methods used to identify the various compounds formed. The identities were confirmed by comparison with known synthetic compounds. Eighteen compounds were identified in the decomposing corn residues. Of these, salicylaldehyde, and butyric, phenylacetic, and 4-phenylbutyric acids were “volatile”, and benzoic,p-hydroxybenzoic, vanillic, ferulic,o-coumaric,o-hydroxyphenylacetic, salicylic, syringic,p-coumaric,trans-cinnamic, and caffeic acids were “not volatile”. Resorcinol,p-hydroxybenzaldehyde, and phloroglucinol were also found. In the decomposing rye residues, nine compounds were identified, including vanillic, ferulic, phenylacetic, 4-phenylbutyric,p-coumaric,p-hydroxybenzoic, salicylic, ando-coumaric acids, and salicylaldehyde. In the lettuce seed bioassay, most of the above compounds from corn and rye decomposition products exhibited some phytotoxicity. Phenylacetic, 4-phenylbutyric, salicylic, benzoic, ando-hydroxyphenylacetic acids were highly inhibitory to the growth of lettuce at concentrations between 25 and 50 ppm. The others reduced growth significantly at 100 ppm. Most of the phototoxic spots were located in theR
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0.37–0.97 zone when developed in 2% acetic acid solvent.
TL;DR: Findings are novel in that growth of cells from dissociated periodontal ligament, elucidation of the origin of monolayers derived from connective tissue cells ofperiodontalligament, and cell culture of epithelium derived from this source have not previously been reported.
TL;DR: A “necessary-gate” hypothesis is proposed regarding the relationship between awareness of the CS-UCS relationship and autonomic classical conditioning, which is that awareness is a necessary but not sufficient condition, and a gate but not analog condition, for human differential autonomic Classical conditioning.
Abstract: A “necessary-gate” hypothesis is proposed regarding the relationship between awareness of the CS-UCS relationship and autonomic classical conditioning. The hypothesis is that awareness is a necessary but not sufficient condition, and a gate but not analog condition, for human differential autonomic classical conditioning. Evidence in support of the hypothesis is reviewed and directions for future research and theory development are suggested.
TL;DR: One hundred and eightynine husbands and wives pairs separately completed lengthy questionnaires examining such things as their satisfaction with life, marriage and job; experienced job and life pressures; mental and physical well-being; and communication with their spouses as discussed by the authors.
Abstract: One hundred and eighty-nine husband and wife pairs separately completed lengthy questionnaires examining such things as their satisfaction with life, marriage and job; experienced job and life pressures; mental and physical well-being; and communication with their spouses. Fifty-three of the wives (28 percent) were employed full or part time, making it possible to determine the effects of wives' employment status on individual and pair measures of satisfaction and performance. In general, working wives were more satisfied and performed more effectively than nonworking wives; conversely, husbands of working wives were less satisfied and performed less effectively than husbands of nonworking wives. Some reasons for the greater stress of the husbands in their adjustment to the two-career family situation are offered.