Showing papers by "University of California published in 1981"

Some suggestions for measuring predictive performance

Abstract: The performance of a prediction or measurement method is often evaluated by computing the correlation coefficient and/or the regression of predictions on true (reference) values. These provide, however, only a poor description of predictive performance. The mean squared prediction error (precision) and the mean prediction error (bias) provide better descriptions of predictive performance. These quantities are easily computed, and can be used to compare prediction methods to absolute standards or to one another. The measures, however, are unreliable when the reference method is imprecise. The use of these measures is discussed and illustrated.

Understanding the dose-effect relationship: clinical application of pharmacokinetic-pharmacodynamic models.

Abstract: It is a major goal of clinical pharmacology to understand the dose-effect relationship in therapeutics. Much progress towards this goal has been made in the last 2 decades through the development of pharmacokinetics as a discipline. The study of pharmacokinetics seeks to explain the time course of drug concentration in the body. Recognition of the crucial concepts of clearance and volume of distribution has provided an important link to the physiological determinants of drug disposition. Mathematical models of absorption, distribution, metabolism and elimination have been extensively applied, and generally their predictions agree remarkably well with actual observations. However, the time course of drug concentration cannot in itself predict the time course or magnitude of drug effect. When drug concentrations at the effect site have reached equilibrium and the response is constant, the concentration-effect relationship is known as pharmacodynamics. Mathematical models of pharmacodynamics have been used widely by pharmacologists to describe drug effects on isolated tissues. The crucial concepts of pharmacodynamics are potency — reflecting the sensitivity of the organ or tissue to a drug, and efficacy — describing the maximum response. These concepts have been embodied in a simple mathematical expression, the Emax model, which provides a practical tool for predicting drug response analogous to the compartmental model in pharmacokinetics for predicting drug concentration.

Evidence for magnetic field reconnection at the Earth's magnetopause

Abstract: Eleven passes of the ISEE satellites through the frontside terrestrial magnetopause were identified, where the plasma velocity in the magnetopause and boundary layer was substantially larger than in the magnetosheath. The nature of the plasma flow, magnetic field, and energetic particle fluxes in these regions were examined, with a view to determining whether the velocity enhancements can be explained by magnetic field reconnection.

Structure of the low‐latitude boundary layer

Abstract: Observations at high temporal resolution of the frontside magnetopause and plasma boundary layer, made with the LASL/MPE fast plasma analyzer onboard the ISEE 1 and 2 spacecraft, revealed a complex quasiperiodic structure of some of the observed boundary layers. A cool tailward streaming boundary layer plasma was seen intermittently, with intervening periods of hot tenuous plasma which has properties similar to the magnetospheric population. While individual encounters with the boundary layer plasma last only a few minutes, the total observation time may extend over one hour or more.

Evaluation of methods for estimating population pharmacokinetic parameters II. Biexponential model and experimental pharmacokinetic data

Abstract: Individual pharmacokinetic parameters quantify the pharmacokinetics of an individual, while population pharmacokinetic parameters quantify population mean-kinetics, interindividual variability, and residual variability, including intraindividual variability and measurement error. Individual pharmacokinetics are estimated by fitting individual data to a pharmacokinetic model. Population pharmacokinetic parameters have been estimated either by fitting all individuals' data together as though there were no individual kinetic difference, the naive pooled data (NPD) approach, or by fitting each individuals' data separately and then combining the individual parameter estimates, the two stage (TS) approach. A third approach, NONMEM, takes a middle course between these. This study provides further evidence of NONMEM's validity by comparing, using simulation, the three approaches on three types of data sets corresponding to three typical types of pharmacokinetic studies. The estimates of population parameters provided by the NPD method are poorer than those provided by either of the other methods. The estimates provided by the TS method are adequate for mean values and for residual variability, but not for interindividual kinetic variability. NONMEM's estimates are as good as those of the TS method for mean parameters and for residual variability, and considerably better for interindividual variability. The latter estimates are still not acceptable in an absolute sense. This is probably due, not to an intrinsic fault of the method (as it is in the case of the TS approach), but to an insufficient number of individuals being studied.

Optical-Field-Induced Birefringence and Freedericksz Transition in a Nematic Liquid Crystal

Abstract: Optical-field-induced birefringence in nematic 4-cyano-4′-pentylbiphenyl was measured with cw pump and probe beams, and the optical-field-induced Freedericksz transition was observed for the first time. The results are in quantitative agreement with the theoretical prediction.

The GABA postsynaptic membrane receptor-ionophore complex

Abstract: The function of the inhibitory neurotransmitter, γ-aminobutyric acid (GABA), has been implicated in the mode of action of many drugs which excite or depress the central nervous system. Many convulsant agents appear to block GABA action whereas anticonvulsants enhance GABA action. Some of these drug effects involve altered G AB A-mediated synaptic transmission at the level of GABA biosynthesis, release from nerve endings, uptake into cells, and metabolic degradation. A greater number of agents of diverse classes appear to affect GABA action at the postsynaptic membrane, as determined from both electrophysiological and biochemical studies. The recently developed in vitro radioactive receptor binding assays have led to a wealth of new information about GABA action and its alteration by drugs. GABA inhibitory transmission involves the regulation, by GABA binding to its receptor site, of chloride ion channels. In this GABA receptor-ionophore system, other drug receptor sites, one for benzodiazepines and one for barbiturates/picrotoxinin (and related agents) appear to form a multicomponent complex. In this complex, the drugs binding to any of the three receptor categories are visualized to have an effect on GABA-associated chloride channel regulation. Available evidence suggests that the complex mediates many of the actions of numerous excitatory and depressant drugs showing a variety of pharmacological effects.

Calcitonin selectively stimulates 25-hydroxyvitamin D3-1 alpha-hydroxylase in proximal straight tubule of rat kidney.

Abstract: We have reported previously that the 25-hydroxyvitamin D3 (25(OH)D3)-1α-hydroxylase (1α(OH)ase) activity was localized exclusively in the proximal convoluted tubules (PCT) in mature vitamin D-deficient rats and that the enzyme activity was largely abolished by parathyroidectomy in the vitamin D-deficient rats with presumed secondary hyperparathyroidism1. However Akiba et al.2 found enzyme activity in both PCT and the proximal straight tubules (PST) of the fetal rabbit kidney. Parathyroid hormone and calcitonin, when given in vivo, can stimulate the production of 1α, 25(OH)2D3 from 25(OH)D3 in vitamin D-deficient rats3–6, and, moreover, their in vivo effects on the 1α(OH)ase in thyroparathyroidectomized vitamin D-deficient rats are additive6, a finding consistent with different sites of action of these two hormones. In addition, plasma calcitonin levels are elevated in the fetus of several mammalian species7–10, while they are likely to be low in hypocalcaemic vitamin D-deficient rats. From these observations, we hypothesized that calcitonin could be responsible for stimulating enzyme activity in the PST while parathyroid hormone primarily activates 1α(OH)ase in the PCT. To test this hypothesis, we examined the effect of calcitonin on the 1α(OH)ase activity in defined nephron segments of vitamin D-deficient rats. We report here that the hormone selectively stimulates 1α(OH)ase activity in the PST, whereas this enzyme activity is undetectable in control vitamin D-deficient animals.

Affine manifolds with nilpotent holonomy

Abstract: An affine manifold is a differentiable manifold together with an atlas of coordinate charts whose coordinate changes extend to affine automorphisms of Euclidean space. These charts are called atline coordinates. A map between affine manifolds is called affine it its expression in affine coordinates is the restriction of an aftine map between vector spaces. Thus we form the category of affine manifolds and affine m_nps. Let M be a connected affine manifold of dimension n-> 1, locally isomorphic to the vector space E. Its universal covering/~/ inheri ts a unique affine structure for which the covering projection/~/--~ M is an aifine immersion. The group ~r of deck transformations acts on /V/by afline automorphisms. It is well known that there is an affine immersion D :/~5/--~ E, called the developing map. This follows, for example, from Chevalley's Monodromy Theorem; a proof is outlined in Section 2. Such an immersion is unique up to composition with an atiine automorphism of E. Thus for every g ~ "n" there is a unique affine automorphism a(g) of E such that D o g =ct(g)oD. The resulting homomorphism a : ~r --~ Aft (E) from 7r into the group of affine automorphisms of E is called the affine holonomy representation. It is unique up to inner automorphisms of Aft (E). The composition A : 7r ~ G L (E) is called the linear holonomy representation. The affine structure on M is completely determined by the pair (D, a) . M is called complete when D is a homeomorphism. This is equivalent to geodesic completeness of the connection on M (in which parallel transport is locally defined by affine charts as ordinary parallel transport in E). It is notorious that compactness does not imply completeness. The main results of this paper are about aftine manifolds whose affine holonomy groups a(Tr) are nilpotent. An important class of such manifolds are the affine nilmanifolds 7r\G. Here 7r is a discrete subgroup of a simply connected nilpoint Lie group G. It is assumed that G has a left-invariant afline structure; the space of right cosets of r then inherits an affine structure.

Biotin deficiency: an unusual complication of parenteral alimentation.

Abstract: BIOTIN deficiency has been documented in human beings only in association with prolonged ingestion of raw egg white In this paper, we report that clinically important biotin deficiency occurred in

Photosynthetic activity of phytoplankton in tropical African soda lakes

Abstract: The soda lakes of tropical Africa are recognized as among the world’s most productive ecosystems (e.g., Likens 1975; Cole 1979) largely on the basis of the work of Talling et al. (1973) and Melack & Kilham (1974). These investigators reported exceptionally high rates of photosynthesis derived from dissolved oxygen changes in bottles and in free water. For example, the maximal photosynthetic rate measured by Talling et al. in Lake Aranguadi (Ethiopia) was 30 g O2 m-3h-1, and a rate of 36 g O2 m-2d-1 was calculated by Melack & Kilham from diel free water analyses in Lake Nakuru (Kenya). More recently, Melack (1979a) reported similar rates for the phytoplankton of Lake Simbi (Kenya).

The Experimental Evidence for Subjective Referral of a Sensory Experience Backwards in Time: Reply to P. S. Churchland

Abstract: Our experimental investigations of cerebral neuronal activities that might uniquely be part of the processes that elicit a conscious sensory experience, produced evidence for the hypothesis that two remarkable temporal factors govern this kind of mind-brain relationship (see Libet 1973, 1978a; Libet et al. 1979). (1) There is a substantial delay before cerebral activities, initiated by a sensory stimulus, achieve “neuronal adequacy” for eliciting any resulting conscious sensory experience. For stimuli close to the threshold level for sensation the delay would average approximately 500 msec; for stronger stimuli this delay could be reduced, possibly to as little as 100 msec. The response in question is the introspective awareness of a localized somatic sensation elicited by the stimulus, as reported by the subject. It is in the category of a subjective “raw feel” (e.g., Feigl 1960), as distinct from behavioral responses to a stimulus that could reflect a form of detection that may be unaccompanied by a conscious, subjective experience (Libet 1965). (2) After neuronal adequacy is achieved, the subjective timing of the experience is (automatically) referred backwards in time, utilizing a “timing signal” in the form of the initial response of cerebral cortex to the sensory stimulus. This initial response is represented by the primary evoked potential, an electrophysiological response recordable at the primary sensory cortical area that receives the earliest (as well as the most localized) neural message, within 10 to 20 msec after the peripheral sensory nerve fibers are excited by the stimulus. The experience would thus be “antedated”, and its timing would appear to the subject to occur without the actual substantial delay required before neuronal adequacy for eliciting the experience is achieved.

Predicting individual phenytoin dosage.

Abstract: Most previously suggested methods for predicting phenytoin dosage from steady-state drug levels (Cpss)measured in the clinical setting fail to fully exploit all relevant (population) information. A Bayesian prediction method, applicable to any drug, is available. It appropriately combines all types of information. In this paper, we compare the Bayesian method as applied to phenytoin to two other prediction methods (and a baseline, nonfeedback one). Actual doses are compared to predictions in 49 patients. Each method is optimized, as far as possible, for the test data. The comparison favors the Bayesian method. Since each of the other prediction methods for phenytoin can be shown to be a theoretically suboptimal special case of the Bayesian one, the superiority of the latter may be a general phenomenon. Because the pharmacokinetic model linking steady-state phenytoin levels and dosage is so simple, a good approximation of the general Bayesian method can be implemented as a graphical device, or as a program for a programmable calculator. We present and describe both of these approximations.

Finite Deformation of Elastic Rods and Shells

Abstract: The objective of this paper is to present an account of recent developments in the direct formation of theories of rods and shells based on 1- and 2-dimensional continuum models originating in the works of Duhem and E. and F. Cosserat. Following some preliminaries and description of (3-dimensional) shell-like and rod-like bodies, the rest of the paper is arranged in two parts namely Part A (for shells) and Part B (for rods) and can be read independently of each other. In each part, after providing the main ingredients of the direct model and a statement of the conservation laws, a rapid outline is given of the derivation of the basic equations and nonlinear constitutive equations for elastic materials. Each part also includes a discussion of constrained theories and an account of recent developments on the subject.

Plasmapheresis and immunosuppressive drug therapy in scleroderma.

Abstract: In an uncontrolled clinical trial, plasmapheresis combined with prednisone and cyclophosphamide therapy produced clinical improvement in 14 of 15 scleroderma patients with varying degrees of skin and internal organ involvement. All improved patients showed a gradual loosening of hide-bound skin, relaxation of contractures, and healing of cutaneous ulcers, when present. Severe gastrointestinal symptoms were ameliorated in 4 patients, severe polymyositis was largely reversed in 2 patients, and pulmonary and cardiac function was improved in others. After initial improvement, however, 2 patients died during the period of study and another withdrew unimproved. Antinuclear antibody (ANA) liters declined relatively more than total IgG levels with plasmapheresis in 6 of the 9 patients who had elevated titers. Increased levels of endothelial cell cytotoxic activity found in 11 of the 15 patients were significantly reduced by plasmapheresis. Elevated levels of circulating immune complexes were found in only 4 of the 15 patients. Skin biopsies from adjacent sites taken before and after plasmapheresis in 10 patients all showed less swollen dermal collagen with increased ground substance between collagen bundles in the second biopsy. Although the effects of plasmapheresis cannot be dissociated from those of the immunosuppressive drug therapy, our results suggest that plasmapheresis combined with immunosuppressive drug therapy may find a place in the management of patients with moderate to severe scleroderma. This study implicates circulating factors in the pathogenesis of the disease.

Alcohol production and recovery

Abstract: Alcohol production is receiving increasing attention as a potential transportation fuel. The main feedstocks for the fermentative production of ethanol by yeast are sugar, starch and cellulosic feedstocks. Conventional ethanol production technology by fermentation is reviewed, and the conventional distillation of ethanol from the broth is described. New advances in feedstock preparations including starch and cellulosic raw materials are reviewed and their impact on their fermentation is assessed. Continuous fermentation and continuous fermentation with cell recycle provide opportunities for more efficient alcohol production. Alternatives to energy intensive conventional distillation of alcohol include two-pressure distillation and various novel techniques such as dehydration and solvent extraction. A review of alcohol production economics is included.

Hierarchies of sets and degrees below 0

Abstract: We examine two hierarchies of sets below 0' based on the number of changes a recursive approximation to a set needs to make. Both are generalizations of the notion of being r.e. The first classifies sets by asking what functions dominate the number of changes, as previously set out in Epstein [4]. This extends the ideas of Putnam on trial and error predicates [8]. The second views the changes as dominated by a constructive ordinal, as first suggested by Addison [i], and developed by Ershov [6]. We provide a translation between them and relate these hierarchies to the degrees of unsolvability i 0'.

Actinide-specific sequestering agents and decontamination applications

Abstract: LBL-11533 C Preprint To be published as a Book Chapter in Structure and Bonding Vol. 43, 1980, Springer-Verlag, Heidelberg. West Germany . ACTINIDE-SPECIFIC SEQUESTERING AGENTS AND DECONTAMINATION APPLICATIONS William L. Smith and Kenneth N. Raymond July 1980 TWO-WEEK LOAN COP This is a Library Circulating Copy which may be borrowed for two weeks. Prepared for the U.S. Department of Energy under Contract W-7405-ENG-48

Plane-Strain Testing of Sand

Abstract: Sand was tested under triaxial conditions, plane strain conditions, and conditions where the intermediate principal strain (∈ 2 ) varied between the limits for triaxial and plane strain. Tests were performed using a variety of specimen sizes and shapes, a range of densities from loose to dense, and a range of confining pressures from 70 to 3450 kN/m 2 (10 to 500 psi). The results of these tests provide useful guidelines for plane strain testing of cohesionless soils: (1) Plane strain and triaxial test results differ most for dense specimens tested at low pressures, (2) Plane strain equipment need not be elaborate. Specimens with square cross sections and simple lubricated end plates can be used for plane strain tests, and (3) The end plates need not enforce a condition of perfect plane strain. Tests with values of ∈ 2 as large as 40 percent of the axial strain at failure result in essentially the same value of the angle of internal friction (Φ) as do perfect plane strain tests.

Distribution, transport, and fate of the insecticides malathion and parathion in the environment

Abstract: The environmental dynamics of pesticides are influenced largely by the various factors operating in the environment and the physicochemical and biological properties of pesticides. In the broad sense, the environment is divided into four major components, namely, atmosphere (air), hydrosphere (water), lithosphere (soil), and biosphere (biota), each possessing its own physical and chemical and/ or biological properties. The biotic and abiotic elements in each component influence the dynamics of pesticides. The environmental dynamics of pesticides are further influenced by the physicochemical properties of pesticides. Such properties of pesticides as hydro- or lipo-philicity, partition coefficients, adsorption or chemiosorption, vapor pressure, and volatility determine the ultimate fate of pesticides in the living and nonliving portions of the sytems.

Hippocampal glutamate receptors

Abstract: For years, the hippocampus has been the privileged domain of anatomists and electrophysiologists for investigating various neurobiological processes. The present review deals with recent work which shows that this structure is also well suited to study the role of glutamate as a neurotransmitter and more particularly the characteristics of glutamate receptors and their possible involvement in hippocampal function. After a brief description of the main anatomical features of the hippocampus, we attempt a critical evaluation of the electrophysiological studies of hippocampal glutamate receptors. We then describe the properties of Na-independent 3H-glutamate binding sites in hippocampal membranes, and discuss the possibility that these binding sites are related to postsynaptic glutamate receptors. Finally we show that these binding sites are extremely labile and that hippocampal membranes possess various mechanisms which regulate their number. In particular we develop the idea that the calcium-stimulation of 3H-glutamate binding in hippocampal membranes may be the mechanism by which electrical activity regulates the number of glutamate receptors at hippocampal synapses and thus induces long-lasting changes in synaptic transmission.

Effect of Modified Atmosphere Storage on C. Botulinum Toxigenesis and the Spoilage Microflora of Salmon Fillets

Abstract: Modified atmosphere (MA) storage in conjunction with refrigeration has been shown to significantly increase the shelf life of fresh fish and other products, but the effects, if any on the outgrowth and toxigenesis of C. botulinum are unknown. A commercial system was duplicated in the laboratory and the effects of modified atmosphere on the outgrowth of C. botulinum types A, B, and E were observed in inoculated salmon fillets and sandwiches stored at 4.4°C and 22.2°C. Inoculated samples stored in air at the same temperatures were used as controls. No toxigensis was observed in either the air or modified samples stored at 4.4°C, but all inoculated samples held at 22.2°C were toxic within 2–3 days. Spoilage generally preceded toxigenesis. In a concurrent study, the tendency of CO2 environments to repress the growth of gram negative bacteria to a greater extent than gram positive bacteria was also noted.

The Imagination of Reality Essays in Southeast Asian Coherence Systems

Abstract: Buku ini merupakan kumppulan essay-essay tentang budaya dan sistem yang ada di Asia Tenggara. Berbagai kebiasaan yang dilakukan di Asia khususnya Asia Tenggara, mengundang para peneliti melakukan penelitian tentang kesamaan kebiasaan di negara-negar asia tenggara.

Equilibrium and stability of collisionless systems in the paraxial limit

Abstract: A study is made of the equilibrium and stability of a magnetically confined collisionless plasma in the paraxial or ‘long, thin’ limit. The main field is poloidalaxisymmetric, and a stabilizing quadrupole field is superimposed.

Deoxynucleotide linkers to be attached to a cloned dna coding sequence

Abstract: The present invention is based upon a general principle of providing specific olingonucleotide segments («linkers», herein) to be attached in sequence to a cloned DNA coding segment. The linkers of the present invention confer desired functional properties on the expression of the protein coded by the coding sequence. Using linkers of the present invention, the desired protein may be expressed either as a fusion or non-fusion protein. A linker coding for an additional sequence of amino acids may be attached, the sequence being chosen to provide properties exploitable in a simplified purification process. A linker coding for an amino acid sequence of the extended specific cleavage site of a proetolytic enzyme is provided, as well as specific cleavage linkers for simple specific cleavage sites.