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Showing papers by "University of North Carolina at Chapel Hill published in 1981"


Book ChapterDOI
01 Jan 1981
TL;DR: In this article, a three-point charge model (on hydrogen and oxygen positions) with a Lennard-Jones 6-12 potential on the oxygen positions only was developed, and parameters for the model were determined from 12 molecular dynamics runs covering the two-dimensional parameter space of charge and oxygen repulsion.
Abstract: For molecular dynamics simulations of hydrated proteins a simple yet reliable model for the intermolecular potential for water is required. Such a model must be an effective pair potential valid for liquid densities that takes average many-body interactions into account. We have developed a three-point charge model (on hydrogen and oxygen positions) with a Lennard-Jones 6–12 potential on the oxygen positions only. Parameters for the model were determined from 12 molecular dynamics runs covering the two-dimensional parameter space of charge and oxygen repulsion. Both potential energy and pressure were required to coincide with experimental values. The model has very satisfactory properties, is easily incorporated into protein-water potentials, and requires only 0.25 sec computertime per dynamics step (for 216 molecules) on a CRAY-1 computer.

5,336 citations



Journal ArticleDOI
19 Mar 1981-Nature
TL;DR: It is proposed that this morphogenetic rearrangement of extracellular matrices is the primary function of fibroblast traction and explains its excessive strength.
Abstract: To make visible the traction forces exerted by individual cells, we have previously developed a method of culturing them on thin distortable sheets of silicone rubber1. We have now used this method to compare the forces exerted by various differentiated cell types and have examined the effects of cellular traction on re-precipitated collagen matrices. We find that the strength of cellular traction differs greatly between cell types and this traction is paradoxically weakest in the most mobile and invasive cells (leukocytes and nerve growth cones). Untransformed fibroblasts exert forces very much larger than those actually needed for locomotion. This strong traction distorts collagen gels dramatically, creating patterns similar to tendons and organ capsules. We propose that this morphogenetic rearrangement of extracellular matrices is the primary function of fibroblast traction and explains its excessive strength.

875 citations


Journal ArticleDOI
TL;DR: Equilibria of distribution of amino acid side chains, between their dilute aqueous solutions and the vapor phase at 25 degrees C, have been determined by dynamic vapor pressure measurements, and hydration potentials are more closely correlated with the relative tendencies of the various amino acids to appear at the surface of globular proteins than had been evident from earlier distribution studies on the free amino acids.
Abstract: Equilibria of distribution of amino acid side chains, between their dilute aqueous solutions and the vapor phase at 25 degrees C, have been determined by dynamic vapor pressure measurements. After correction to pH 7, the resulting scale of "hydration potentials", or free energies of transfer from the vapor phase to neutral aqueous solution, spans a range of approximately 22 kcal/mol. The side chain of arginine is much more hydrophilic than those of the other common amino acids, with an equilibrium constant of approximately 10(15) for transfer from the vapor phase to neutral aqueous solution. Hydration potentials are more closely correlated with the relative tendencies of the various amino acids to appear at the surface of globular proteins than had been evident from earlier distribution studies on the free amino acids. Both properties are associated with a pronounced bias in the genetic code.

853 citations


Journal ArticleDOI
TL;DR: In this article, an instrumental version of zone electrophoresis carried out in 75 μm I.D. glass capillaries is described, which demonstrates excellent resolution of charged substances in a short time.

809 citations


Journal ArticleDOI
TL;DR: The theory of elliptically contoured distributions is presented in an unrestricted setting, with no moment restrictions or assumptions of absolute continuity as mentioned in this paper, where the distributions are defined parametrically through their characteristic functions and then studied primarily through the use of stochastic representations which naturally follow from the work of Schoenberg on spherically symmetric distributions.

695 citations


Journal ArticleDOI
TL;DR: An important role for active Na+ transport in the maintenance of the epithelial barrier function can be postulated after extensive electrophysiological and morphological work done in recent years.
Abstract: The ability of an epithelium to prevent permeation of noxious agents has not been well studied except in the gastrointestinal tract where exclusion of H+ has clinical significance. This article reviews the permeation routes across epithelia both as elucidated in the extensive electrophysiological work done in recent years and as demonstrated in morphological studies. We thus place concepts about gastrointestinal barrier function into the framework of transport physiology. Both the permeability and permselectivity of epithelial barriers are reviewed here. The effects of physical agents (pressure and electric current), polyvalent cations, organic compounds with both specific (channel blocking) and nonspecific (detergent) membrane properties, cyclic nucleotides, microfilament-active agents, and particularly H+ on both the barrier function (permeability and permselectivity) and transport function of epithelia are considered. Based on the available data, an important role for active Na+ transport in the maintenance of the epithelial barrier function can be postulated.

632 citations


Journal ArticleDOI
20 Nov 1981-Science
TL;DR: When two small doses of ethanol were administered to pregnant mice during the gastrulation stage of embryogenesis, the embryos developed craniofacial malformations closely resembling those seen in the human fetal alcohol syndrome.
Abstract: When two small doses of ethanol were administered to pregnant mice during the gastrulation stage of embryogenesis, the embryos developed craniofacial malformations closely resembling those seen in the human fetal alcohol syndrome. Striking histological changes appeared in the developing brain (neuroectoderm) within 24 hours of exposure. Decreased development of the neural plate and its derivatives apparently accounts for the craniofacial malformations. The critical exposure period is equivalent to the third week in human pregnancy.

616 citations


Journal ArticleDOI
TL;DR: The increased respiratory-epithelial potential differences appear to be a specific abnormality in homozygotes for cystic fibrosis, which suggests that absorption of excess salt and perhaps liquid from respiratory epithelial surfaces contributes to the pathogenesis of lung disease in cysts fibrosis.
Abstract: To investigate respiratory epithelial function in cystic fibrosis, we measured the transepithelial electrical potential difference across the upper and lower respiratory mucosa in patients with cystic fibrosis and control subjects. The nasal potential difference in the 24 patients with cystic fibrosis exceeded by more than 3 standard deviations the mean voltage in healthy controls, subjects with other diseases, and subjects heterozygous for cystic fibrosis. Potential differences in lower airways were measured in four patients and were significantly greater than in controls (P less than 0.05). Superfusion of the luminal surface with amiloride, an inhibitor of active sodium absorption, induced greater reductions in both nasal and airway potential difference in patients than in controls. We conclude that the increased respiratory-epithelial potential differences appear to be a specific abnormality in homozygotes for cystic fibrosis. The greater reduction in potential difference in response to amiloride suggests that absorption of excess salt and perhaps liquid from respiratory epithelial surfaces contributes to the pathogenesis of lung disease in cystic fibrosis.

583 citations


Journal ArticleDOI
TL;DR: In this paper, the concept of coproduction of public services has captured increased attention as a potential means of increasing the effectiveness and efficiency of local government, and the concept has been explored in an effort to sharpen the definition of that concept and add rigor to our understanding of the effects of COProduction in local service delivery and processes by which coproductive activity occurs.
Abstract: The concept of coproduction of public services has captured increased attention as a potential means of increasing the effectiveness and efficiency of local government. In this article we explore the concept of coproduction in an effort to sharpen the definition of that concept and add rigor to our understanding of the effects of coproduction in local service delivery and the processes by which coproductive activity occurs.

558 citations


Journal ArticleDOI
TL;DR: The results demonstrate ELI in neurons which are heterogeneous in size, some probably functioning as interneurons and others as projection neurons in different areas of the CNS, suggesting that these pentapeptides serve diverse functions which include, in addition to nociception, the regulation of neuroendocrine, respiratory, auditory, vestibular, and olfactory functions.
Abstract: The immunocytochemical localization of enkephalin-like immunoreactivity (ELI) throughout the rat central nervous system (CNS) was investigated. The detection of ELI-containing structures was facilitated through the use of (1) brains from colchicine-treated rats, (2) the proteolytic pretreatment of sections with pronase and (3) the “double-bridge” staining technique. Our findings confirm the presence of ELI in perikarya, neuronal processes and terminals in many areas of the CNS. In addition, the localization of ELI-containing perikarya is reported for the first time in the following areas: the olfactory bulb, the olfactory tubercle, the lateral preoptic nucleus, several nuclei within the amygdaloid nuclear complex, the hippocampus, the neocortex, the cingulate cortex, the posterior mammillary nucleus, the medial nucleus of the optic tract, the brachium of the inferior colliculus, the ventral tegmental nucleus, the locus ceruleus, the subceruleal region, the lateral trapezoid nucleus, the nucleus reticularis lateralis, and lamina VII of the cervical spinal cord. Our results demonstrate ELI in neurons which are heterogeneous in size, some probably functioning as interneurons and others as projection neurons in different areas of the CNS. The location of these neurons within the brain suggests that these pentapeptides serve diverse functions which include, in addition to nociception, the regulation of neuroendocrine, respiratory, auditory, vestibular, and olfactory functions.

Journal ArticleDOI
TL;DR: The carcinogenic hazard of oral snuff is of special concern in view of the recent upswing in consumption of smokeless tobacco in the United States.
Abstract: A case–control study in North Carolina involving 255 women with oral and pharyngeal cancer and 502 controls revealed that the exceptionally high mortality from this cancer among white women in the South is primarily related to chronic use of snuff. The relative risk associated with snuff dipping among white nonsmokers was 4.2 (95 per cent confidence limits, 2.6 to 6.7), and among chronic users the risk approached 50-fold for cancers of the gum and buccal mucosa — tissues that come in direct contact with the tobacco powder. In the absence of snuff dipping, oral and pharyngeal cancer resulted mainly from the combined effects of cigarette smoking and alcohol consumption. The carcinogenic hazard of oral snuff is of special concern in view of the recent upswing in consumption of smokeless tobacco in the United States. (N Engl J Med. 1981; 304: 745–9.)

Journal ArticleDOI
TL;DR: Although there were many common properties of the lines, each line had a unique profile of the parameters evaluated and most likely reflects the individuality of the tumors of origin and individual genotypes and capacity for a range of phenotypic expression of the cells.
Abstract: Six new permanent cell lines were established from human gliomas and compared to nine other cell lines from human gliomas. All fifteen lines had individually distinct HLA phenotypes and all but two, which were from a black patient, had type B glucose-6-phosphate-de;hydrogenase isoenzymes. Morphologically, the lines could be classified into four patterns descriptively designated as fibroblastic, fascicular, epithelial, or glial. Four of the lines grew progressively and could be serially transplanted when injected into athymic mice; two others grew initially and then regressed. From none to 100% of cells developed elongated tapering processes and showed reduction in nuclear-cytoplasmic ratio in the presence of 1 mM cyclic AMP and theophylline. Levels of 2'-3' cyclic nucleotide 3'-phosphohydrolase activity ranged from nondetectable to 12.78 +/- 1.49 micromoles 2' AMP formed per hr mgm total protein. None of the lines had detectable S-100 protein, but two had readily demonstrable glial fibrillary acidic protein in indirect immunofluorescence. Fibronectin levels in spent culture supernatants ranged from undetectable levels to 21.4 micrograms/ml/10(5) cells. All but one line shared surface antigens with normal human adult or fetal brain, as detected in absorption analyses with nonhuman primate antiserum raised against glioblastoma multiforme tissue or cell line U-251 MG. Although there were many common properties of the lines, each line had a unique profile of the parameters evaluated. This heterogeneity most likely reflects the individuality of the tumors of origin and individual genotypes and capacity for a range of phenotypic expression of cells.


Journal ArticleDOI
TL;DR: The widespread but selective distribution of these neurons suggests that somatostatin is not only a hypothalamic regulator of neuroendocrine function, but may also function as a major neuromodulator mediating a variety of functions throughout the central nervous system.

Journal ArticleDOI
TL;DR: In this article, a graphical model of forest composition based on elevation and topographic-moisture gradients was constructed using 305 0.1 ha samples, where stands were stratified into eight 200 m elevation belts, and then ordinated by correspondence analysis using understory data.
Abstract: The forest vegetation of the northern Colorado Front Range was studied using a combination of gradient analysis and classification methods. A graphical model of forest composition based on elevation and topographic-moisture gradients was constructed using 305 0.1 ha samples. To derive the topographic moisture gradient, stands were stratified into eight 200 m elevation belts, and then ordinated by correspondence analysis using understory (<1 m) data. Each of the resultant gradients was scaled against a standard site moisture scalar derived from incident solar radiation and topographic position. Except for krummholz sites, the vegetation defined gradients fit the moisture scalar closely. Once scaled, these gradients were stacked vertically, sandwich-style, to create the graphical representation shown in Figure 5.


Journal ArticleDOI
TL;DR: Acute alcohol use resulted in less severe toxic reactions than in those patients without acute alcohol use and those patients with no history of chronic alcohol use, and no consistent difference in hepatotoxicity could be demonstrated.
Abstract: • Six hundred sixty-two consecutive patients with acetaminophen overdoses were evaluated. Those at risk on the basis of their acetaminophen blood levels, as plotted on the study nomogram, were treated with oral acetylcysteine. Statistically significant differences in severity of hepatic toxicity were observed between patients treated within 16 hours after ingestion and those treated between 16 and 24 hours after ingestion. No deaths occurred among patients treated within 24 hours of ingestion, except for one patient who was an alleged gunshot homicide. Seven percent of patients with plasma acetaminophen levels in the potentially toxic range and treated with acetylcysteine within ten hours of ingestion showed transient SGOT level elevations, whereas 29% of those treated between ten and 16 hours after ingestion and 62% of those treated between 16 and 24 hours after ingestion showed such transient toxicity. No consistent difference in hepatotoxicity could be demonstrated between those patients with a history of chronic alcohol use and those patients with no history of chronic alcohol use. Acute alcohol use resulted in less severe toxic reactions than in those patients without acute alcohol use. (Arch Intern Med141:380-385, 1981)

Journal ArticleDOI
20 Feb 1981-Science
TL;DR: Hypothalamic command signals are primarily responsible for the proportional driving of locomotion and respiration during exercise in paralyzed animals.
Abstract: Unanesthetized decorticate cats walked or ran normally on a treadmill either spontaneously or during electrical stimulation of the subthalamic "locomotor" region. The respiratory response usually preceded the locomotor response and increased in proportion to locomotor activity despite control or ablation of respiratory feedback mechanisms. Respiration increased similarly in paralyzed animals during fictive locomotion despite the absence of muscular contraction or movement. Hypothalamic command signals are thus primarily responsible for the proportional driving of locomotion and respiration during exercise.

Journal ArticleDOI
TL;DR: β-Endorphin-containing neurons in the rat central nervous system were localized using three improvements of the unlabelled antibody-enzyme bridge immunocytochemical technique.
Abstract: beta-Endorphin-containing neurons in the rat central nervous system were localized using three improvements of the unlabelled antibody-enzyme bridge immmunocytochemical technique. These improvements were (1) the use of brains from colchicine-treated rats; (2) the proteolytic pretreatment of sections with pronase, and (3) a 'double-bridge' staining procedure. In addition to the known localization of beta-endorphin-like immunoreactivity in perikarya in the medial basal hypothalamus, we have observed nerve fibers and terminals with beta-endorphin-like immunoreactivity to be more widely distributed than reported in previous studies. This includes discrete areas of the septal, preoptic, hypothalamic, thalamic and subthalamic regions, the amygdala, the periaqueductal gray, the inferior colliculus, the nucleus tegmenti pontis, the nucleus raphe dorsalis, several regions of the reticular formation, the locus ceruleus, the parabrachial nuclei, the mesencephalic trigeminal nucleus, the nucleus raphe magnus, the solitary tract and the nucleus of the solitary tract. The distribution of beta-endorphin-like immunoreactivity is in good agreement with many of the physiological, neuroendocrine and behavioral effects attributed to this peptide such as analgesia, the regulation of the release of pituitary hormones, thermoregulation and feeding behavior. This implicates beta-endorphin as an important neurotransmitter or modulator with specific functions within the central nervous system.

Journal ArticleDOI
TL;DR: The results of this study suggest that measurement of plasma somatomedin C provides a sensitive indicator of nitrogen loss and may be useful in monitoring the changes in protein metabolism that occur during alterations in nutritional status.
Abstract: We have assessed the effect of fasting for 10 days on plasma concentrations of immunoreactive somatomedin C and urinary urea excretion in seven obese male volunteers. From a mean prefast value of 0.83 U/ml, plasma somatomedin C fell to 0.21 U/ml after 10 days of fasting. A prompt increase was observed with refeeding. The change in somatomedin C during fasting showed a highly significant correlation with the change in urinary urea nitrogen excretion (r = 0.74; P < 0.001). It also was shown that inhibitors which interfere with quantitation in somatomedin bioassays are not observed in the RIA for somatomedin C. The results of this study suggest that measurement of plasma somatomedin C provides a sensitive indicator of nitrogen loss and may be useful in monitoring the changes in protein metabolism that occur during alterations in nutritional status.

Journal ArticleDOI
TL;DR: The phase of menstrual life in which transition occurs from relatively regular cycles to the termination defined as menopause is studied for several hundred women who have kept accurate records of their menstrual flows.

Journal ArticleDOI
01 Jun 1981-Cell
TL;DR: The results suggest that most of the periplasmic and outer-membrane proteins share a common step in localization before the polypeptide becomes accessible to the processing enzyme.

Journal ArticleDOI
TL;DR: This article defined the tragedy of the commons as a decision-making problem under uncertainty, and defined the assurance problem as an alternative to private exclusive property rights, which can solve the problem of overexploitation.
Abstract: Institutional alternatives to common property externalities are wider than argued by private exclusive property rights advocates. The "tragedy of the commons" is not a prisoners' dilemma, characterized by the strict dominance of individual strategies. The nonseparable common property externality is an "assurance problem." The assurance problem provides striking perspectives in analytical and policy terms. It redefines the problem of the commons as one of decision making under uncertainty. Institutional rules innovated by the group to reduce uncertainty and coordinate expectations can solve the problem of overexploitation. Rules come in many forms, and private property is only one.

Journal ArticleDOI
TL;DR: These studies provide a model system for studying the humoral and nonhumoral factors that control the biosynthesis of somatomedin by human tissues and should lead to a better understanding of the mechanisms controlling human fibroblast growth.
Abstract: Human growth hormone (hGH) is known to be a potent stimulator of somatomedin secretion in vivo. The induction of somatomedin by growth hormone has been difficult to study in vitro, however, because no organ containing a high concentration of somatomedin has been identified. Because fetal mouse explants have been shown to produce somatomedin in vitro, we have undertaken studies to determine whether postnatal human fibroblast monolayers also produce somatomedin, and if so, whether its production is regulated by other hormones. Quiescent human fibroblasts were exposed to serum-free minimum essential medium, and the medium was assayed for somatomedin concentration using a specific radioimmunoassay for somatomedin-C. A progressive rise in immunoreactive somatomedin to 0.08 U/ml per 105 cells per 24 h was observed over 72 h of incubation. This was an underestimation of the actual concentration of immunoreactive somatomedin since the amount measured following acid treatment was at least fourfold higher than in the untreated medium. Growth hormone stimulated immunoreactive somatomedin production in a dose-dependent manner: 5 ng hGH/ml = 0.1 U/ml per 105 cells; 50 ng hGH/ml = 0.25 U/ml per 105 cells. Platelet-derived growth factor and fibroblast growth factor were also stimulatory, but epidermal growth factor, thyroxine, or cortisol had no effect. Media that had been exposed to human fibroblasts stimulated DNA synthesis in BALB/c 3T3 fibroblasts (a cell type that does not produce somatomedin). Medium-derived immuno-reactive somatomedin eluted from Sephacryl S-200 in two major peaks (150,000 and 8,000 mol wt). The higher molecular weight peak is similar to the one observed when whole serum was used. These studies provide a model system for studying the humoral and nonhumoral factors that control the biosynthesis of somatomedin by human tissues. Since immunoreactive somatomedin production may be a rate-limiting factor for fibroblast growth, the delineation of the hormonal control of somatomedin production should lead to a better understanding of the mechanisms controlling human fibroblast growth.

Journal ArticleDOI
TL;DR: In this article, the ecdysteroid titer of Manduca sexta was characterized by large increases lasting approximately 24 and 60 hours, respectively, and these peaks occurred just before ecdysis.

Journal ArticleDOI
TL;DR: This paper presented an overview of an approach to the quantitative analysis of qualitative data with theoretical and methodological explanations of the two cornerstones of the approach, Alternating Least Squares and Optimal Scaling.
Abstract: This paper presents an overview of an approach to the quantitative analysis of qualitative data with theoretical and methodological explanations of the two cornerstones of the approach, Alternating Least Squares and Optimal Scaling. Using these two principles, my colleagues and I have extended a variety of analysis procedures originally proposed for quantitative (interval or ratio) data to qualitative (nominal or ordinal) data, including additivity analysis and analysis of variance; multiple and canonical regression; principal components; common factor and three mode factor analysis; and multidimensional scaling. The approach has two advantages: (a) If a least squares procedure is known for analyzing quantitative data, it can be extended to qualitative data; and (b) the resulting algorithm will be convergent. Three completely worked through examples of the additivity analysis procedure and the steps involved in the regression procedures are presented.

Journal ArticleDOI
TL;DR: This article found that infants between 10.5 and 16.5 months of age were studied with their mothers in a setting containing six special stimulus objects and found that a majority of infants pointed, usually vocalizing or looking at their partner while pointing, and the communicative function of pointing was further established by the partner's response of verbal acknowledgment and looking at the object.
Abstract: This study sought to discover the age at which infants call interesting objects to another's attention by pointing, to relate their ability to follow another's pointing to their own use of the gesture, and to compare the uses of pointing and reaching. Infants between 10.5 and 16.5 months of age were studied with their mothers in a setting containing six special stimulus objects. By 12.5 months, a majority of infants pointed, usually vocalizing or looking at their partner while pointing. The communicative function of the gesture was further established by the partner's response of verbal acknowledgment and looking at the object. The ability to follow another's points seemed to be acquired before the infants began to point but improved with their own use of the gesture. Reaching partook of the behaviors associated with pointing but developed earlier and decreased as pointing increased. The data show that at an early age infants exhibit an elementary form of the ability to take the visual perspective of others. When adults point to an event or object of interest at some distance, they extend an arm and index finger toward it, usually comment briefly on what is being singled out, and then check to see that their partner is looking in the correct direction. Thus, the act of pointing can be said to consist of three components: the gesture itself, a relevant verbal utterance, and visual monitoring of the intended recipient of the message. At what age do children begin to point spontaneously for apparently the same purpose

Journal ArticleDOI
TL;DR: In this paper, Fick's first law was used to calculate the diffusive mobilities of dissolved ammonium, phosphate and phosphate ion pairs in an organic-rich anoxic sediments of Cape Lookout Bight.

Journal ArticleDOI
TL;DR: No correlation was observed between the virulence of different strains or colony types of gonococci and the ability to scavenge iron in vitro from transferrin or other chelators and theAbility of Neisseria species to use iron compounds and to compete with iron-binding proteins was examined with deferrated defined medium and the iron chelator deferoxamine.
Abstract: The ability of Neisseria species to use iron compounds and to compete with iron-binding proteins was examined with deferrated defined medium and the iron chelator deferoxamine. All Neisseria species were able to assimilate a variety of ferric and ferrous iron salts. They were not able to efficiently solubilize an inorganic iron salt such as ferric nitrate, but were able to use iron chelated by citrate, oxalacetate, pyrophosphate, or nitrilotriacetate. Each of the 95 Neisseria isolates examined was able to use hemin as a sole source of iron, and most, but not all, of the isolates were able to obtain iron from hemoglobin. Heated human serum stimulated growth of all gonococci, meningococci, and some commensal Neisseria species in iron-deficient medium. All gonococci and meningococci were able to scavenge iron from 25% saturated transferrin, whereas most commensal organisms were inhibited by this iron-binding protein. The ability to compete with transferrin was specific, since partially saturated conalbumin was bacteriostatic for all Neisseria species. Although the pathogenic Neisseria species were able to compete more efficiently with transferrin for iron than were the nonpathogenic Neisseria species, no correlation was observed between the virulence of different strains or colony types of gonococci and the ability to scavenge iron in vitro from transferrin or other chelators.