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At least 1,387 records · Page 77Linked to original sources
PubMed1986

Robust modulation of [3H]dopamine release from rat striatal slices by D-2 dopamine receptors.

Conflicting results have been reported for D-2 dopamine (DA) receptor modulation of DA release from rat striatal slices. After systematic examination of the assay conditions used to evoke release of [3H]DA, we report robust modulation of calcium-dependent stimulation-evoked 3H-overflow by D-2 receptors in rat striatal slices preloaded with [3H]DA. In the presence of the DA uptake inhibitor, nomifensine, the amount of 3H-overflow evoked by low numbers (15-30) of pulses was not dependent on the frequency of stimulation (0.25-3.0 Hz). When larger numbers (60-300) of pulses were applied, 3H-overflow was related inversely to the frequency of stimulation. In contrast, 3H-overflow increased linearly as the total number of pulses applied was increased when examined at any of these frequencies. Nomifensine (10 microM) augmented 3H-overflow at each level of stimulation while only slightly increasing spontaneous release. Modulation of evoked 3H-overflow by S-sulpiride, a selective D-2 DA receptor antagonist, was dependent on the number of pulses delivered, rather than on the frequency of stimulation. In contrast, modulation by pergolide, a selective D-2 DA receptor agonist, was dependent on stimulation frequency. S-sulpiride produced greater augmentation of 3H-overflow after delivery of low numbers of pulses in the presence of nomifensine. However, pergolide produced greater inhibition of 3H-overflow at low frequencies of stimulation in the absence of nomifensine. These results indicate that D-2 receptors in rat striatum modulate DA release and are most effective when a low concentration of endogenous DA is present in the synaptic cleft.

Animals↗
PubMed1985

A new change-in-ratio procedure robust to unequal catchability of types of animal.

The change-in-ratio technique is a useful practical procedure for the estimation of game animal population sizes. The major problem with this technique is failure of the assumption that both types of animals are captured or sighted with equal probabilities. Here we extend the change-in-ratio technique to the case where there are two removals with emphasis on the special situation where there are two consecutive single-type removals. The advantage of this extension is that it allows an estimation procedure which is robust to unequal capture or sighting probabilities. It is also possible to test the assumption of equal sighting probabilities. Some numerical results on mean squared error of the population size estimator for the new design and the traditional design are given. The procedure is illustrated on some juvenile grass carp data collected in a small pond where the population size is known. We believe this technique is potentially useful to wildlife and fisheries biologists and that more statistical research would be beneficial.

Animal Population Groups↗
PubMed1985

Prothrombin time proficiency testing: a robust grading method.

A robust two-way analysis of variance technique was applied to determine simultaneously the effects of method and thromboplastin on prothrombin time. A new approach to outlier detection for two-way analysis of variance was used. Focusing on the underlying error structure improved the uniformity of the grading procedure in the hematology proficiency testing program of the New York State Department of Health. The logarithm-transformed scale produced constancy of error variance and resulted in uniformity of the acceptable spread of data. The common variance was lower than that obtained by previous methods and allowed for a narrower acceptable range of reported prothrombin times by reducing the inflated standard deviation, thus improving the efficiency of the grading procedure. For proficiency testing, no advantage was found in the use of either a common thromboplastin or freeze-dried, coumadinized patient plasmas rather than artificially depleted commercial plasmas, except for special purposes.

Automation↗
PubMed1979

The application of robust calibration to radioimmunoassay.

The minute concentrations of many biochemically and clinically important substances are currently estimated by radioimmunoassay (RIA). Traditionally, the most popular approaches to the statistical analysis of RIA data have been to linearize the data through transformation and fit the calibration curve using least squares or to directly fit a nonlinear calibration curve using least squares. Estimates of the hormone concentration in patients are then obtained using this curve. Unfortunately, the transformation is frequently unsuccessful in linearizing the data. Furthermore, the least squares fit can lead to erroneous results in both approaches since the many sources of error which exist in the RIA process often result in outlier observations. In this paper, an approach to the analysis of RIA data which incorporates robust estimation methods is described. An algorithm is presented for obtaining the M-estimates of nonlinear calibration curves. The curves to be fitted are modified hyperbolae based on 12 to 16 observations. A procedure, based on the application of the Bonferroni Inequality, is presented for obtaining tolerance-like interval estimates of the concentration of the hormone of interest in the patients. Results of simulations are cited to support the method of construction of confidence bands for the fitted calibration curve. Data obtained from the Veteran's Hospital, Buffalo, New York are used to illustrate the application of the algorithm which is presented.

Calibration↗
PubMed1978

Efficiency and robustness of pedigree segregation analysis.

Different pedigree structures and likelihoods are examined to determine their efficiency for parameter estimation under one-locus models. For the cases simulated, family size has little effect; estimates based on unconditional likelihoods are generally more efficient than those based on conditional likelihoods. The proposed method of pedigree analysis under a one-locus model is found to be robust in the analysis of nuclear families: skewness of the data and polygenic inheritance will not lead to the spurious detection of major loci unless they occur simultaneously, and together with a moderate amount of environmental correlation among sibs.

Gene Frequency↗
PubMed1983

Robust estimation of population size in closed animal populations from capture-recapture experiments.

In this paper the problem of finding robust estimators of population size in closed K-sample capture-recapture experiments is considered. Particular attention is paid to models where heterogeneity of capture probabilities is allowed. First, a general estimation procedure is given which does not depend on any assumptions about the form of the distribution of capture probabilities. This is followed by a detailed discussion of the usefulness of the generalized jackknife technique to reduce bias. Numerical comparisons of the bias and variance of various estimators are given. Finally, a general discussion is given with several recommendations on estimators to be used in practice.

Animals↗
PubMedDate not supplied

Model systems for oxidative drug metabolism studies. Catalytic behavior of water-soluble metalloporphyrins depends on both the intrinsic robustness of the catalyst and the nature of substrates.

Sulfonated manganese and iron porphyrins have been used as catalysts in attempts to mimick the oxidation of acetaminophen and two ellipticine derivatives by horseradish peroxidase. Cofactors were potassium monopersulfate for the synthetic catalyst and hydrogen peroxide for the natural enzyme. Hindered metalloporphyrins, i.e. with ortho positions of the meso-phenyl rings substituted with methyl groups [iron(III) and manganese(III) derivatives of octasodium mesotetrakis(3,5-disulfonatomesityl)porphyrin], were shown to be at least 10 times more robust than unsubstituted derivatives [iron(III) and manganese(III) derivatives of tetrasodium meso-tetrakis(4-sulfonatophenyl)porphyrin] when activated in the absence of substrate. The catalytic activity depends on the nature of the substrate as shown by a decrease or an increase in reactivity observed, respectively, in the oxidation of acetaminophen or ellipticine derivatives catalyzed by hindered metalloporphyrins compared with nonhindered ones. Only sterically hindered metalloporphyrins, even in the case of lowered reactivity, were allowed to mimick the behavior of horseradish peroxidase when activated in the absence of substrate (stability toward autodegradation) and in the course of repeated infusion of substrate (retained catalytic activity as time advances).

Acetaminophen↗
PubMed1994

Robust estimation of gene frequency and association parameters.

Methods based on generalized estimating equations are proposed for estimation and testing of gene frequency and association parameters using family data. In the problems considered, a marginal model is used to estimate the gene frequency and association parameters specified in the marginal distributions of the individuals. These procedures are robust in the sense that consistent estimates of the parameters of interest and their standard errors are obtained even though the marginal model is not fully correctly specified. In addition, the methods are shown to have good efficiency when compared with maximum likelihood methods. Specific procedures for application of the methods to the cases of allele frequency estimation, testing of linkage and Hardy-Weinberg disequilibrium parameters, and testing for marker-disease association are outlined and illustrated with data examples.

Alleles↗
PubMed1994

Intrathalamic rhythmicity studied in vitro: nominal T-current modulation causes robust antioscillatory effects.

Thalamocortical oscillations mediate both physiological and pathophysiological behaviors including sleep and generalized absence epilepsy (GA). Reciprocal intrathalamic circuitry and robust burst firing, dependent on underlying transient Ca current (IT) in thalamic neurons, support generation of such rhythms. In order to study the regulation of intrathalamic rhythm generation and the effects of GA anticonvulsants previously shown to reduce IT in acutely isolated thalamic neurons, we developed an in vitro rat thalamic slice preparation that retains sufficient intrathalamic circuitry to support evoked oscillations (range = 2.0-4.6 Hz, average = 2.7, n = 38), associated with burst firing in the thalamic reticular nucleus (nRt) and thalamic relay neurons. Extracellular stimulation of nRt evoked in relay neurons a biphasic inhibitory response with prominent GABAA and GABAB receptor-mediated components. The GABAA component was picrotoxin sensitive, outwardly rectifying and Cl- dependent, with a very negative reversal potential (-94 mV), indicating that an active extrusion mechanism exists in these cells to keep [Cl-]i < 5 mM. The GABAB component had a linear conductance, a reversal potential of -103 mV, and was quite long lasting (about 300 msec) so that rebound bursts often were generated on its decay phase, presumably leading to reexcitation of nRt through known excitatory connections. GABAB-mediated responses thus provide a timing mechanism for promoting slow intrathalamic oscillations. Reduction of IT (30-40%) by succinimides slightly increased the threshold for burst generation in relay and nRt cells, but there was little effect on either number of spikes/burst or intraburst frequency, and there were no other direct effects on other measures of cellular excitability. Intrathalamic oscillations were significantly reduced by these agents through a slight decrease in burst probability of thalamic neurons. We conclude that interactions between the intrinsic properties of thalamic neurons and intrathalamic circuitry lead to generation of slow oscillations. A similar mechanism may underlie the pathophysiological 3 Hz spike and wave EEG activity that characterizes GA. Furthermore, anti-GA drugs such as ethosuximide probably exert their action by reducing the burst-firing probability of neurons within populations of reciprocally interconnected relay and nRt neurons, thus producing a desynchronization of the thalamic circuit that prevents spike/wave generation.

Animals↗
PubMed1993

Robust survival of isolated bovine adrenal chromaffin cells following intrastriatal transplantation: a novel hypothesis of adrenal graft viability.

Previous investigations have demonstrated that adrenal chromaffin cells survive poorly when grafted into the striatum of rodents, nonhuman primates, and patients with Parkinson's disease. This poor survival has been attributed to the low levels of endogenous NGF within the striatum. However, chromaffin cells isolated from the nonchromaffin constituents of the adrenal medulla (fibroblasts and endothelial cells) have recently been demonstrated to survive grafting into a number of CNS sites. The present study determined whether nonchromaffin constituents of the adrenal medulla may be responsible for poor graft survival. We compared the survival of intrastriatally grafted isolated bovine chromaffin cells with that observed following implantation of either perfused adrenal medullary suspensions containing all adrenal medullary cell types or isolated chromaffin cells that were then reseeded with autologous fibroblasts and endothelial cells. Implants of perfused adrenal medullary cells survived poorly and most graft sites were infiltrated with macrophages. The chromaffin cells in this group that did survive appeared to be in the process of degeneration. In contrast, large numbers of isolated chromaffin cells survived for up to 2 months following transplantation. These cells maintained their endocrine phenotype and stained for all enzymatic markers of catecholamine synthesis as well as chromogranin A. Morphologically, these cells resembled chromaffin cells seen in situ and the perigraft region was essentially devoid of macrophages. When isolated chromaffin cells were reseeded with autologous fibroblasts and endothelial cells, the implants degenerated and few, if any, surviving chromaffin cells were observed. Interestingly, these latter grafts induced a host-derived sprouting response of tyrosine hydroxylase-immunoreactive fibers. These data demonstrate that large numbers of adrenal chromaffin cells can survive intrastriatal implantation in the absence of exposure to exogenous NGF. Rather, the nonchromaffin cells of the adrenal medulla (fibroblasts and endothelial cells) appear to compromise the viability of grafted chromaffin cells. Once they are eliminated from the graft, robust survival of chromaffin cells occurs. If clinical trials employing adrenal medullary grafts are still to be considered for the treatment of Parkinson's disease, isolation of the chromaffin cells should be considered to enhance graft viability.

Adrenal Medulla↗
PubMed1993

The robustness of infant haptic memory: testing its capacity to withstand delay and haptic interference.

The robustness of infant haptic memory was assessed in terms of its capacity to withstand either a brief delay or potential retroactive "interference" from other haptic input. 48 infants (mean age 8 months) were familiarized haptically to a small cube or sphere with smooth or rough surface texture and subsequently tested for recognition of the shape and texture of this stimulus in terms of the relative level of haptic response to 3 test stimuli, comprising the familiar stimulus, a new-shape stimulus, and a new-texture stimulus. The test stimuli were presented (a) immediately, (b) after a 5-min delay, or (c) after a second familiarization or "interference" phase involving another haptic stimulus different in shape and texture to the first. The infants demonstrated recognition of shape and texture in the No Delay condition, of shape and (marginally) of texture in the Delay condition, but only of texture in the Interference condition. The greater susceptibility of shape to interference was considered in terms of the degree of similarity among the shapes employed in the study.

Cognition↗
PubMed1993

A robust strategy for screening and confirmation of familial defective apolipoprotein B-100.

The diagnosis of familial defective apolipoprotein B-100 (FDB) has been facilitated by the use of mutagenic polymerase chain reaction (PCR) primers to introduce restriction sites at the FDB gene locus. We describe a two-test strategy for diagnosing FDB that overcomes the potential for error in single-test methods based on such techniques. We introduce an Sau96I restriction site for PCR products of the normal apolipoprotein B allele. Incomplete digestion of the PCR product with Sau96I suggests an FDB heterozygote, although a false-positive result due to nonideal digestion conditions remains a possibility. In such cases we use a second test that introduces an ScaI restriction site in PCR products of the FDB allele. The diagnosis is confirmed if half of this product can be digested with ScaI. Both tests use 0.25 units of Taq polymerase and are robust with respect to annealing temperature (31-58 degrees C) and to Mg2+ concentration (1.0-3.2 mmol/L).

Apolipoprotein B-100↗
PubMed1993

Robust and inexpensive equipment design for polymerase chain reaction detection of sequence mutations. Cystic fibrosis in a mother and 2 children analysed.

Every polymerase chain reaction (PCR) requires use of a temperature cycler for about 3 hours. Since there are many diagnostic tests using this technology, it is important that robust but inexpensive machinery is available. Such a stand-alone machine has been designed and used to analyse an interesting family in which a mother and her 2 children were diagnosed as having cystic fibrosis.

Adult↗
PubMed1996

Establishing the robustness of short-tandem-repeat statistics for forensic applications.

Before the introduction of a four-locus multiplex short-tandem-repeat (STR) system into casework, an extensive series of tests were carried out to determine robust procedures for assessing the evidential value of a match between crime and suspect samples. Twelve databases were analyzed from the three main ethnic groups encountered in casework in the United Kingdom: Caucasians, Afro-Caribbeans, and Asians from the Indian subcontinent. Independence tests resulted in a number of significant results, and the impact that these might have on forensic casework was investigated. It is demonstrated that previously published methods provide a simple procedure for correcting allele frequencies--and that this leads to conservative casework estimates of evidential value.

Alleles↗
PubMed1996

Exploring the functional robustness of an enzyme by in vitro evolution.

The evolution of natural proteins is thought to have occurred by successive fixation of individual mutations. In vitro protein evolution seeks to accelerate this process. RNA hypermutagenesis, cDNA synthesis in the presence of biased dNTP concentrations, delivers elevated mutant and mutation frequencies. Here lineages of active enzymes descended from the homotetrameric 78 residue dihydrofolate reductase (DHFR) encoded by the Escherichia coli R67 plasmid were generated by iterative RNA hypermutagenesis, resulting in >20% amino acid replacement. The 22 residue N-terminus could be deleted yielding a minimum functional entity refractory to further changes, designating it as a determinant of R67 robustness. Complete substitution of the segment still allowed fixation of mutations. By the facile introduction of multiple mutations, RNA hypermutagenesis allows the generation of active proteins derived from extant genes through a mode unexplored by natural selection.

Amino Acid Sequence↗
PubMed1996

A robust edge detection method for gated radionuclide ventriculograms.

UNLABELLED: We present a myocardial edge detection technique that was developed for fast, reproducible measurements of left ventricular ejection fraction in the clinical setting. METHODS: This myocardial edge detection method compares three edge parameters--count amplitude and first and second count derivatives--in three consecutive locations along a radius to a predetermined template of these values. Each of the radii, defined at 10-degree intervals, has different template values that permit accurate edge detection even though adjacent structures, such as the left atrium and the right ventricle, alter edge parameters. The template for edge detection is based on either the average edge parameters determined from manually defined edges in 15 patients (automatic method) or an operator-defined edge in the first frame (semiautomatic method). RESULTS: The edge detection methods were tested in 100 patients, and intraobserver variabilities as well as comparison with clinically obtained ejection fractions were calculated. The standard error of the estimate was less than 3.1% for all observer comparisons. In 15 patients with both high-count (400,000 counts per image) and low count (50,000 counts per image) studies, the mean absolute difference in ejection fraction was 2.6% for intraobserver comparisons. CONCLUSION: A robust myocardial edge detection technique was developed that is applicable for routine clinical use.

Erythrocytes↗
PubMed1997

Robust, but transient expression of adeno-associated virus-transduced genes during human T lymphopoiesis.

Recombinant adeno-associated viruses (rAAV) have been proposed to be gene transfer vehicles for hematopoietic stem cells with advantages over other virus-based systems due to their high titers and relative lack of dependence on cell cycle for target cell integration. We evaluated rAAV vector containing a LacZ reporter gene under the control of a cytomegalovirus (CMV) promoter in the context of primary human CD34+CD2- progenitor cells induced to undergo T-cell differentiation using an in vitro T-lymphopoiesis system. Target cells from either adult bone marrow or umbilical cord blood were efficiently transduced, and 71% to 79% CD2+ cells expressed a LacZ marker gene mRNA and produced LacZ-encoded protein after exposure to rAAV-CMV-LacZ. The impact of transgene expression on the differentiation of T cells was assessed by sequential quantitation of immunophenotypic subsets of virus-exposed cells and no alteration was noted compared with control. The durability of transgene expression was assessed and found to decay by day 35 with kinetics dependent on the multiplicity of infection. In addition, vector DNA was absent from CD4 or CD8 subselected CD3+ cells by DNA-polymerase chain reaction. These data suggest that rAAV vectors may result in robust transgene expression in primitive cells undergoing T-cell lineage commitment without toxicity or alteration in the pattern of T-cell differentiation. However, expression is transient and integration of the transgene unlikely. Recombinant AAV vectors are potentially valuable gene transfer tools for the genetic manipulation of events during T-cell ontogony but their potential in gene therapy strategies for diseases such as acquired immunodeficiency syndrome is limited.

Antigens, CD↗
PubMed1997

Robust analysis of within-unit variances in repeated measurement experiments.

The objective of some experiments is to compare the within-unit variances of two or more treatments, products, or techniques. In this situation, a repeated measurement design involving a random effects model, with possibly heterogeneous variances, is appropriate. Under the assumption that the random errors have a normal or a multivariate t-distribution, this design was analyzed in Chinchilli, Esinshart, and Miller (1995, Biometrics 51, 215-216). However, the resulting methodology is quite vulnerable to skewness and outliers. We propose two distribution-free procedures that are quite robust for balanced designs when the number of repeated measurements is the same for all units and for all treatments. We then show how these procedures are modified to handle unbalanced situations. We illustrate the methodology with an example from a trial comparing serum cholesterol measurements from a routine laboratory analyzer with those of a standardized method.

Analysis of Variance↗