Showing papers by "Dartmouth College published in 1973"

Endocrine and metabolic effects of experimental obesity in man.

Abstract: Publisher Summary This chapter discusses the endocrine and metabolic effects of the experimental obesity in humans. All the changes witnessed in spontaneous obesity except for the increase in adipocyte number have been reproduced in experimental obesity. It has been found that endocrine and metabolic changes are associated with gain in weight. Normal subjects fattened by eating a mixed diet require more calories in relation to their body surface area for maintenance of the obese state than they require when at their natural weight and also more than the spontaneously obese generally require. There are marked differences in the ability of normal individuals to gain weight by taking calories in excess of those required for maintenance. When weight is gained by normal increase in the intake of fat alone, there is a higher proportion of weight gained to calories ingested, and the weight gained may be maintained by an intake that is no greater than that required to maintain the initial weight. The chapter also describes the hormonal and circulating factors that affect the resistance to insulin in experimental obesity. It also presents evidence for cellular factors in resistance to insulin in experimental obesity and their response to gain in weight and to dietary carbohydrate.

Enzymatic Catalysis and Transition-State Theory

Abstract: The application of transition-state theory to enzymatic catalysis provides an approach to understanding enzymatic catalysis in terms of the factors that determine the strength of binding of ligands to proteins. The prediction that the transition state should bind to the enzyme much more tightly than the substrate is supported by the experimental results with stable analogs of transition states. Transition-state analogs have great potential for use in understanding enzymatic catalysis and in inhibiting enzymes. Because of their potency and specificity as enzyme inhibitors, some of them may become very useful chemotherapeutic agents.

Ecological energetics of the seaweed zone in a marine bay on the Atlantic coast of Canada. III. Energy transformations by sea urchins

Abstract: An energy budget was constructed for a population of the sea urchin Strongylocentrotus droebachiensis in the nearshore area of St. Margaret's Bay, Nova Scotia, Canada. Of the 6 age classes identified, ages 1+and 2+accounted for about 1/2 the population energy flow. Population production efficiencies were: production/assimilation=0.28, production/consumption=0.04 to 0.13, and production/biomass=0.80. Although S. droebachiensis was the dominant herbivore in the seaweed bed, it utilized only 1 to 7% of seaweed production. As with other populations of sea urchins, however, it had a proportionately greater influence on seaweed biomass, and also presumably production, by clearing seaweed from large areas of substrate and maintaining it clear. Loss of dissolved organic matter, the only term in the energy budget not measured, was estimated by substracting the other terms in the energy budget from consumption. In laboratory individuals, this ranged from 40 to 80% of absorption (consumption-faeces). A critical review of energy budgets for 6 other species of marine benthic grazers also revealed large amounts of energy unaccounted for that might be attributed to loss of dissolved organic matter.

Quaternary volcanic and tectonic segmentation of Central America

Abstract: Central America is divided into seven segments based on differences in the strikes and positions of volcanic lineaments in the historically active volcanic chain. This block-like pattern is also seen in the contrasting volcano morphology, recent fault patterns and the distribution of shallow earthquakes. Discontinuities in the deep seismic zone can be identified at some segment margins. The boundary areas between the segments are characterized by faulting transverse to the volcanic lineaments, frequently accompanied by basalt cinder cone fields, by concentrations of shallow earthquakes and by catastrophic historic eruptions. This volcanological, structural and seismological data can be explained by a segmented converging plate margin. At shallow depths the underthrust lithosphere is broken along tear faults into 100 to 300 km long segments. The separate segments descend into the mantle with different strikes and dips and give the geology its segmented character. Evidence for similar segmented converging plate margins is found in Mexico and in other parts of the circumpacific and alpine belts.

A Simple Continuous Review Deterministic One-Warehouse N-Retailer Inventory Problem

Abstract: A one-warehouse N-retailer deterministic inventory system is examined. The objective is to determine the stocking policy which minimizes average system cost per unit time over the infinite time horizon. Necessary properties of an optimal policy are derived, and optimal solutions for the one-retailer and N identical retailer problems are given. Heuristic solutions for the general problem are suggested, tested against analytical lower bounds and, on the basis of these tests, found to be near optimal.

Sulfur Dioxide Contributions to the Atmosphere by Volcanoes

Abstract: The first extensive measurements by remote-sensing correlation spectrometry of the sulfur dioxide emitted by volcanic plumes indicate that on the order of 10(3) metric tons of sulfur dioxide gas enter the atmosphere daily from Central American volcanoes. Extrapolation gives a minimum estimate of the annual amount of sulfur dioxide emitted from the world's volcanoes of about 10(7) metric tons.

Normal embryonic stages for salmonid fishes, based on Salmo gairdneri Richardson and Salvelinus fontinalis (Mitchill)

Abstract: As a byproduct of a re-examination of teleost morphogenetic movements, 23 stages in the normal development of salmonid fishes are presented, from fertilization to and beyond hatching, together with rates of their appearance at several constant temperatures. To aid in planning experiments, the period before closure of the germ ring is divided into 13 stages, with detailed discussion of internal structures and movements as well as external features, especially during gastrulation. The literature of salmonid development suggests that the stages are closely applicable to the embryos of any genera of Suborder Salmonoidei. except as to the rates of their appearance. Illustrations are designed for ready identification of stages. Tofacilitate their correlation with the older morphological literature, the principal events of organogenesis in the ectodermal, mesodermal, and endodermal categories are listed according to the stages at which they occur, as determined by dissections and serial sections.

Steroid-binding properties and stabilization of cytoplasmic glucocorticoid receptors from rat thymus cells.

Abstract: 1. A competitive binding assay was adapted for determination of the specific binding of glucocorticoids to cytoplasmic receptors from rat thymus cells. The steroid–receptor complexes prepared by incubation of a cytoplasmic fraction from rat thymus cells with [1,2-3H2]cortisol or with [1,2,4-3H3]triamcinolone acetonide had rates of dissociation at 37°C similar to those from intact cells. 2. The cytoplasmic receptor was unstable at 3°C, but the rate of inactivation was decreased in the presence of 2.5mm-EDTA. The steroid–receptor complex was stable. 3. Rate constants for association and for dissociation, and association constants, were determined for the interactions of cortisol, cortexolone, dexamethasone and triamcinolone acetonide with the cytoplasmic receptor at 3°C. Differences in the association constants for different steroids could largely be accounted for by the differences in the rate constants for dissociation, but the rate constants for association did not vary greatly; the implications of these findings for the nature of the steroid-binding site are discussed. 4. A cytoplasmic fraction prepared from cells which had been incubated at 37°C under anaerobic conditions bound much less [1,2-3H2]cortisol than did a fraction from aerobic cells, but the binding capacity was restored after exposure of the anaerobic cells to O2. 5. The specific binding of [1,2-3H2]-cortisol to intact thymus cells incubated aerobically was not affected by the presence of 0.1mm-cycloheximide, nor did this concentration of cycloheximide inhibit the recovery of specific binding observed when anaerobic cells were transferred to an aerobic atmosphere. 6. The energy dependence of specific binding of cortisol to the receptor is discussed with reference to possible mechanisms.

Electron-Electron Scattering in the Transport Coefficients of Simple Metals

Abstract: The parametrization of simple-metal Fermi surfaces by a set of band gaps leads to a model for umklapp electron-electron (Coulomb) scattering and its contribution to electrical resistivity. We discuss transport coefficients in general, but emphasize electrical resistivity, which would vanish without umklapp processes. We treat deviations from Matthiessen's rule resulting from the energy dependence of the deviation function, for the case in which both electron-electron and electron-impurity scattering are present. The resulting ${T}^{2}$ power law is too small to be seen in polyvalent metals. In potassium, the ${T}^{2}$ term is comparable to the phonon contribution at about 2 \ifmmode^\circ\else\textdegree\fi{}K.

Preference structures I: Distances between transitive preference relations†

Abstract: This paper generalizes the Kemeny‐Snell distance function for distances between weak orderings to a distance function for the collection of all partial orderings of a set. This generalization explains some of the seemingly strange properties of the Kemeny‐Snell distance, and extends it to such important classes of orderings as semiorders and interval orders. In section four I consider possible applications of the distance function and describe a number of problems that arise in attempts to apply the distance function. In section 3 I discuss the concept of a distance function in more general terms and introduce a new distance function defined by a set of axioms different from those given in Section 2.

Studies of volcanic ash from two recent Central American eruptions

Abstract: The 1971 eruptions of Cerro Negro volcano in Nicaragua and Fuego volcano in Guatemala produced ash blankets with minimum volumes of 7 × 107 m3 and 6 × 107 m3, respectively. Seven new chemical analyses show that ash produced by both eruptions was basaltic and similar to previously — erupted lavas of both volcanoes. Both ash blankets were sampled areally and stratigraphically before they were affected by rain. Chemical analyses of soluble materials leached from these ashes show that near the end of both eruptions the concentrations of soluble materials increased by about an order of magnitude. These changes are believed to reflect changes in the composition of eruptive gases.

The use of radioactive isotopes to measure the transfer of materials in aquatic food chains

Abstract: Radioisotopes have been misused extensively by ecologists in transfer studies within food chains. Unless it is known that no recycling of isotope has occurred during the experiment, the assumption of linear uptake when in fact the system is not linear, even over short periods, can lead to significant errors in the estimation of ingestion or feeding. If recycling occurs, at least a 3 or 4-compartment, hydraulic-type model is necessary to even approximate the complicated kinetics of isotopic transfer in a simple aquatic feeding experiment. In any event, it is essential to follow the uptake or loss of an isotope (change in specific activity) as a function of time in at least 1 compartment before deciding on an appropriate model. If experiments are designed so that the maximum number of rate processes are summed or integrated by the animal, the kinetics can be considerably simplified. If the food supply is uniformly labelled, the rate of change of tracer can be used to give a rate of ingestion (grazing). If the predator is labelled with a suitable isotope before starting the experiment, the rate of loss of its isotope burden under different experimental conditions can be used to determine respiration or excretion rates, turnover rates, ingestion, and the size and number of major compartments in the transfer system.

Kinetics of diffusion-controlled reaction between chemically asymmetric molecules. II. Approximate steady-state solution

Abstract: The previously published equation for the rate of a diffusion-limited bimolecular reaction between chemically asymmetric molecules is studied numerically for the case that one of the reactant molecules is uniform. The results are reproduced quite well by a simple approximate chemical-kinetic steady-state scheme and, in principle, allow estimates of the size of the reactive region and of the activation-controlled rate to be made from the observed dependence of rate on solvent viscosity. The simple scheme is easily generalized to the case of two nonuniform reactants. In general, restriction of reactivity to some fraction of the molecular surface (i.e., a steric factor) must reduce the observable reaction rate, but to an extent which is moderated by the rotational diffusion of the reactant molecules.

Soluble Material on Ash from Active Central American Volcanoes

Abstract: Eruptions of six active volcanoes in Central America provided 57 volcanic ash samples in the past 7 yrs which were unaffected by rain. The ash samples were leached with water which was analyzed for Cl, F, SO4, Na, Ca, Mg, K, Mn, Zn, and Cu, all of which were usually present. The analytical data were examined in terms of time of eruption, eruptive cycle, and physical character of the vent. It was found that the leachate material came primarily from the surface of ash particles, consisted of chemicals commonly found in volcanic gases and sublimates, and was more abundant in ash from a deep vent. It was concluded that much of the soluble material was deposited on the ash surface from volcanic gas during eruption. Isopach mapping indicated that the total amount of ash falling within the 2.5-mm-thickness contour during the 48-day eruption of Cerro Negro in 1968 was 17 million tons; more than 21,000 tons of soluble material were contained in this ash. If projected to the world scale and over geologic time, the soluble material on volcanic ash appears to account for the Cl and SO4 which Rubey (1951) found to be in excess in the oceans.

On the analysis of pharmacological experiments in terms of an allosteric receptor model.

Abstract: According to the usual drug-receptor model, developed by Clark, Gaddum, and Stephenson, one can determine drug-receptor dissociation equilibriun constants and relative efficacies experimentally, by analyzing the drug concentrations which cause equal responses under various conditions. Underlying this analysis is the concept of the "stimulus," which is directly proportional to the fraction of receptors activated the proportionality constant being characteristic of each drug, and being known as the "efficacy." Equal biological responses are assumed to correspond to equal stimuli. Such experiments to determine equieffective drug concentrations circumvent the problem presented by the fact that there is no generally valid theory to interpret the shapes of concentration-response curves. This paper discusses the interpretation of these experiments according to the allosteric receptor model proposed by Karlin. In this model the receptor is assumed to have two conformational states, R and T , normally present in the ratio T/R = L. A drug A is assumed to combine reversibly with each of these two forms, with dissociation equilibrium constants K AR and K AT , respectively, and the biological response is assumed to depend on the proportion of receptors in the R form. The present analysis shows that for competitive drug interactions a "stimulus" can be defined which has exactly the same algebraic form as the "stimulus" in the Clark-Gaddum-Stephenson model; hence the two models are experimentally indistinguishable with respect to competitive drug interactions. The drug-receptor dissociation constant determined by these methods is K AT , and the "efficacy" depend-on the relative affinities of the drug for the R and T forms; i.e., the "efficacy" is K AT /K AR -1. On the other hand, the experimental method utilizing partial irreversible receptor inactivation yields a different apparent dissociation constant, namely, [ K AT -1 + ( K AR L ) -1 ] -1 . By doing different kinds of experiments on two or more drugs, one can in principle determine all the equilibrium constants in the allosteric model. Both models allow for the possibilities of negative efficacy and of nonparallel log concentration-response curves for competitive antagonists with nonzero efficacy. Experimental evidence to date does not clearly rule out either model.

Evidence for Direct Control of Coronary Vascular Tone by Oxygen

Abstract: The interaction between the effects of oxygen and adenosine on acetylcholine-induced contractile tension was observed in helical coronary arterial strips suspended in physiological salt solution It was found that (1) steady-state contractile tension was unaffected or depressed 5-20% when oxygen pressure (Po2) was diminished to levels as low as 5-10 mm Hg, (2) contractile tension was markedly depressed at a Po2 of 0 mm Hg, (3) adenosine-induced relaxation of contractile tension was inversely proportional to Po2 in the tissue bath, and (4) in the presence of adenosine at a concentration just adequate to inhibit contractile tension at a Po2 of 10 mm Hg, contractile tension was directly proportional to bath Po2 The latter two observations were usually most apparent at a Po2 between 10 and 40 mm Hg It is proposed that the vasodilating effect of adenosine on the intact coronary vasculature may be most effective during myocardial hypoxia and that physiological control of coronary vascular tone may be more closely related to variations in local Po2 than to variations in local concentrations of adenosine

Biochemical aspects of colchicine action on meiotic cells.

Abstract: The effect of colchicine on various metabolic processes in meiotic cells was analyzed in order to clarify the mechanism by which the drug reduces chiasma frequency. Synthesis of DNA, RNA, and protein was either unaffected or slightly inhibited during the early stages of meiotic prophase. Such inhibition as did occur could not be related to the achiasmatic effect. DNA synthesis during the pachytene stage was very much reduced in achiasmatic cells. Such reduction appeared to be a consequence and not a cause of the achiasmatic condition. The principal biochemical effect of colchicine was in the reduction of a membrane associated DNA-binding protein which normally appears during meiotic prophase. A basis for this effect was found in the presence of a colchicine binding protein in the nuclear membrane which is distinguishable from its cytoplasmic counterpart by several physicochemical criteria.