Bias in genetic variance estimates due to spatial autocorrelation

Summary A central problem in the analysis of genetic field trials is the dichotomy of genetic and environmental effects because one cannot be defined without the other. Results from 768,000 simulated family trials in complete randomized block designs demonstrated a serious upward bias in estimates of family variance components from multi-unit plot designs when the phenotypic observations were compatible with a first-order autoregressive (AR1) process. The inflation of family variances and, thus, additive genetic variance and narrow sense individual heritabilities progressed exponentially with an increase in the nearest neighbor correlation () in the AR1 process. Significant differences in inflation rates persisted among various plot configurations. At = 0.2 the inflation of family variances reached 48–73%. Inflation rates were independent of the level of heritability. Modified Papadakis nearest neighbor (NN) adjustment procedures were tested for their ability to remove the bias in family variances. A NN-adjustment based on Mead's coefficient of interplant interaction and one derived from Bartlett's simultaneous autoregressive scheme removed up to 97% of the bias introduced by the phenotypic correlations. NN-adjusted estimates had slightly (5–8%) higher relative errors than did unadjusted estimates.     

Increase of plasma membrane oxidoreductase activity is not correlated with the production of extracellular Superoxide radicals in human Namalwa cells

Summary We have considered the regulatory interrelationship of the plasma membrane oxidoreductase (PMOR) system and the mitochondrial respiratory capacity of human Namalwa (lymphoblastoid) cells. To this end, we made use of mitchondrially respiratory competent (⁺) cells and ⁰ cells, which lack mitochondrial DNA (mtDNA) and consequently mitochondrial respiratory activity. NADH-fer-ricyanide reductase activity of the PMOR system is increased 3-fold in ⁰ Namalwa cells compared to ⁺ cells. It is also shown for the first time that addition of coenzyme Q₁₀ and coenzyme Q₁₀-ana-logues, which can rescue ⁰ Namalwa cells in the absence of pyravate, gives rise to a further 2–3-fold increase in plasma membrane NADH-ferricyanide reductase activity. These systems were examined to determine if there exists a correlation between the regulation of the PMOR system and extracellular Superoxide radical formation as measured with the fluorescence probe L-012. No correlation was found between NADH-ferricyanide reductase activity and extracellular Superoxide radical production. PMOR function in cellular proliferation appears therefore not to involve extracellular Superoxide radical production.Abbreviations CoQ₁₀ coenzyme Q₁₀ - EtBr ethidium bromide - HCO-60 polyoxyethylated hydrogenated castor oil - HEPES 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid - mtDNA mitochondrial DNA - L-012 8-amino-5-chloro-7-phenylpyrido(3,4-d)pyridazine-1,4(2H,3H)dione - SOD Superoxide dismutase     

Proteins main-chain atomic displacements and density of stabilizing interactions

The assumption that interactions like hydrogen bonds, that establish the secondary structure of proteins, modulate the local flexibility of the polypeptide chain suggests a phenomenological relation between ²-the X-ray determined variance of the thermally-distributed location of a main-chain atom and the value of — a properly-defined linear density of stabilizing interactions at that location. The functional relation ² 1/ is verified from the data of lysozyme. is constructed from first principles after assuming that the thermal motions of an unstabilized polypeptide chain resemble those of a random chain. Taking the locations and the identity of the stabilizing interactions from literature, the predicted 1/g9 for lysozyme and metmyoglobin is compared with the observed ² along the proteins main-chain. The satisfactory results are discussed in the light of the possible role that hydrogen bonding plays in determining the equilibrium and the dynamic properties of the main-chain structural fluctuations in proteins, and its modelling by using a simplified mechanistic approach.     

Relationship between heterosis and heterozygosity at marker loci: a theoretical computation

Summary In this paper we have studied the linear correlation between a genetic distance index between two parent lines (based on marker loci information) and the heterosis observed in the F₁ hybrid from the two lines, for a quantitative character (determined by several loci, or QTL). Theoretical computations of the correlation coefficient () between the distance index and the heterosis were made, assuming the biallelic model (defined by Fisher). When the alleles at both marker loci and QTL are equally distributed among the whole population of considered lines, the coefficient is a function of the squares of linkage disequilibria between alleles at marker loci and alleles at QTL. The QTL that are not marked by marker loci and marker loci that do not mark any QTL play symmetrical roles and can decrease greatly. We conclude that the prediction of F₁ hybrid heterosis based on marker loci would be more efficient if these markers were selected for their relationship to the alleles implicated in the heterotic traits considered.     

Attraction of Aedes aegypti II. Velocity of reaction to host with and without additional carbon dioxide

The velocity with which Aedes aegypti (L.) reacted to odors from a human arm was the same with and without additional carbon dioxide, and was found to increase asymptotically. The derivative dy/dx=–bX_ln described the velocity of response and was not different from the derivatives of the actual data. CO₂ may exert its main effect within the central nervous system.

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Zusammenfassung Die Geschwindigkeit, mit der Aedes aegypti auf den Geruch eines menschlichen Armes reagierte, war mit und ohne Kohlendioxyd-Zusatz die gleiche und nahm asymptotisch zu. Die Ableitung dy/dx=–bX_ln beschreibt die Geschwindigket der Reaktion und weicht von der Ableitung der aktuellen Versuchsdaten nicht ab. CO₂ mag seine Hauptwirkung innerhalb des Zentralnervensystems entfalten.

     

Yeast mutants resistant to ethidium bromide

Summary Yeast mutants resistant to ethidium bromide have been isolated among sensitive grande cells (⁺) for their ability to grow on glycerol in the presence of the dye. Mutant cells are also resistant to acriflavin and do not yield petites (^-) when grown on galactose with the mutagen. Genetic analysis reveals that resistance to ethidium bromide is controlled by a cytoplasmic factor, carried by, or linked to, the determinant (mitochondrial DNA). The expression of resistance to ethidium bromide seems to be related to the presence in the cell of a product of mitochondrial protein synthesis. It is concluded that some mitochondrial DNA sequence is involved in the resistance to ethidium bromide of yeast mitochondria.     

The effect of population structure on the relationship between heterosis and heterozygosity at marker loci

The relationship between heterozygosity at neutral marker loci and heterosis of F₁ hybrids is investigated using a theoretical model. Results emphasize that linkage disequilibrium between the markers and the loci implicated in heterosis [quantitative trait loci (QTLs) that exhibit dominance effects] is a necessary condition to finding a correlation ( _mh ) between heterozygosity at marker loci and the heterosis. The effect of population structure, in which the parental inbred lines of the hybrids belong to different heterotic groups, is considered. _mh is investigated for: (1) hybrids between lines that belong to the same heterotic group (within-group hybrids); (2) hybrids between lines that belong to different groups (between-group hybrids); and (3) all hybrids, both within and between-groups. Within a group, significant values of ( _mh ) may arise because of linkage disequilibrium generated by drift. At the between-group level, no correlation is expected since link-age disequilibrium should differ randomly from one group to the other, which is consistent with recent experimental results. Possible ways to achieve prediction of the heterosis in this situation are discussed. When all hybrids are considered simultaneously, divergence of allelic frequencies among groups for the markers and the QTLs produces a correlation between heterosis and heterozygosity at marker loci. This correlation increases with the number of markers that are considered.     

Sequence homology and recombination between the genomes of morphologically dissimilar bacteriophages LP 52 and theta

Summary A restriction fragment map of Bacillus licheniformis temperate phage LP 52 DNA (molecular weight 38.5×10⁶) was established, using restriction endonucleases BamHI (8 target sites), BglI (10 sites), BglII (13 sites) and EcoRI (22 sites). The map is linear, with well-defined ends, without any signs of circular permutation. The DNA of a related phage, LP 51, produced identical restriction fragments. At least 62% DNA of LP 52 has been found homologous to the DNA of the recently discovered, morphologically quite dissimilar, phage , as demonstrated by hybridization of electrophoretically separated restriction fragments of DNA. Under the same conditions, the DNAs of LP 52 and of the morphologically similar Bacillus subtilis phage 105 did not cross-hybridize. The homologous regions in the genomes of phages LP 52 and have been shown to be colinear. Comparison of the cleavage maps of phages LP 52 and has shown that, within the regions of homology, not a single restriction fragment and few restriction sites have been conserved during divergent evolution. Three major regions of heterology were defined; the longest one, covering the right-hand end of the map (73±2.75% up to 100% LP 52 genome length) appeared to contain genes coding for structural proteins of the virions; a shorter region at the left-hand end of the map (coordinates zero to 10.3±3.3% LP 52 genome length) and a very short central region (coordinates 41.8–43.9%) could be identified, the latter apparently containing a regulatory locus responsible for the heteroimmune behavior of the two phages. Recombinants between phages LP 52 and were isolated. Mapping of recombinant genomes has indicated mutual substitution of allelic pieces of LP 52 and DNAs upon strict conservation of overall genome length.     

Bias of maximum likelihood estimator of intraclass correlation

Summary A bias correction was derived for the maximum likelihood estimator (MLE) of the intraclass correlation. The bias consisted of two parts: a correction from MLE to the analysis of variance estimator (ANOVA) and the bias of ANOVA. The total possible bias was always negative and depended upon both the degree of correlation and the design size and balance. The first part of the bias was an exact algebraic expression from MLE to ANOVA, and the corrected estimator by this part was ANOVA. It was also shown that the first correction term was equivalent to Fisher's reciprocal bias correction on hisZ scores. The total possible bias of MLE was large for small and moderate samples. Relative biases were larger for small parametric values and vice versa. To ensure a relative bias less than 10% assuming an intraclass correlation of 0.025, which is not unusual in most of the animal genetic studies, the total number of observations (N) should be not less than 500. From a design point of view, minimum bias occurred atn = 2, the minimum family size possible, underN fixed.     

Reversal time distribution in the perception of visual ambiguous stimuli

Reversal of perspective for ambiguous optical stimuli (Necker cube, Schröder staircase, honeycomb) has been studied, determining the statistical distribution of time intervals spent on each percept. The experimental distributions can be fitted with the gamma function, characterized by two parameters n, b. The two parameters are not independent, showing a correlatiomn = 0.74.Subsequent intervals appear to be largely independent; from the beta distribution for the fraction of time spent on a given percept, one can show that the subjects differ only in regard to the variance of this variable.     

Localization of a cruciform cutting endonuclease to yeast mitochondria

We have found a cruciform cutting endonuclease in the yeast, Saccharomyces cerevisiae, which localizes to the mitochondria. This activity apparently is associated with the mitochondrial inner membrane since the activity is not released into solution by osmolysis, in contrast to the matrix enzyme, isocitrate dehydrogenase. The cruciform cutting activity appears to be encoded by CCE1. This gene has been shown to encode one of the major cruciform cutting endonucleases present in a yeast cell. In ccel strains, which lack CCE1 endonuclease activity, the mitochondrial cruciform cutting endonucleolytic activity is also absent. Since CCE1 is allelic to MGT1, a gene required for the highly biased transmission of petite mitochondrial DNA in crosses between ⁺ and hypersuppressive ^– cells, it seems likely that the CCE1 endonuclease functions within mitochondria.     

Induction of respiration deficient mutants in Saccharomyces cerevisiae by Berenil

Summary Some characteristic details of mutagenesis by Berenil, a non-intercalating trypanocidal dye, that govern the change from wild type (⁺) to vegetative petite (^–) in Saccharomyces cerevisiae are presented and contrasted with the intercalating mutagens ethidium bromide and euflavine.The extent and rate of mutagenesis by Berenil is affected by a variety of parameters controlling the cellular and mitochondrial phenotype: among them are exposure to 45°; competition with EB but not euflavine; a requirement for an energy source during and subsequent to exposure to the mutagen; exposure to caffeine; and the presence of genetic blocks in various steps of the mitochondrial repair system for uv-induced lesions. It is, however, insensitive to exposure to Antimycin A. Except for the first of these observations, qualitative differences have emerged between the responses induced by Berenil and the other mutagens, especially ethidium bromide.Using these observations we have postulated a stepwise sequence of events that can account for the mutagenic action of Berenil.Publication No. 2122.     

An approach for parameter estimation of biotechnological processes

An approach for parameter estimators design of biotechnological processes (BTP) is presented in case of lack of real time information about state variables. It is based on general reaction rate models and measurements of at least one reaction rate. A general parameter estimator of BTP is designed with the help of which specific rate estimators are synthesized. Stability and convergence of an estimator of specific growth rate for a class of aerobic batch processes are proved. Its effectiveness is illustrated by simulation results. The proposed on-line parameter estimation approach can be used for design of BTP on-line variable estimation algorithms (variable observers of BTP).List of Symbols X, S, P g/l biomass, substrate and product concentrations - C g/l oxygen concentration in the culture broth - C _sg/l saturation concentration of oxygen in the culture broth - C _in, C_outg/l oxygen concentrations in the input air flow and in the outlet gasphase - F _in, F_outl/h the input air flow in the fermenter and output air flow - OUR g/(lh) oxygen consumption rate - OUR _mg/(lh) measured values of OUR - V l volume - , , l/h specific growth, consumption and synthesis rates - K _La(o) l/h specific volumetric mass transfer coefficient - D l/h dilution rate - R _X, R_S, R_Pg/(lh) biomass growth, substrate consumption and product synthesis rates - K _b matrix of yield coefficients - H_b(), H() matrices of known functions of - H(R) matrix of known functions of R - and gain matrices - a vector of the state variables - () a reactions rates vector, describing qualitative relations among the components - R() a reactions rates vector, describing qualitative and quantitative relations among the components - F a feed rates vector - Q a gaseous outflow rates vector - _b () a vector of unknown functions of - ₁() a vector of functions - (t) a vector of unknown time-varying parameters - ₂(, ) an auxiliary vector-function of and - Y _X/S, Y_X/C, Y_X/P substrate, oxygen and product yield coefficients - b maintenence coefficient - k _i(i=1...6) kinetic coefficients - C _i(i=1,2) design parameters estimate     

Rates of decay for the survival probability of a mutant gene II The multitype case

This paper extends the results of [1] to the multitype case. For a multitype branching process that is slightly supercritical, approximations for the survival probability in terms of the maximal eigenvalue of the mean matrix and a generalized variance ² are developed. Our results improve upon those of Hoppe [5] and Eshel [3] that seek to validate a conjecture of Ewens [4].Research supported in part by NSF grant DMS 9007182     

A restricted maximum likelihood estimator for truncated height samples

A restricted maximum likelihood (ML) estimator is presented and evaluated for use with truncated height samples. In the common situation of a small sample truncated at a point not far below the mean, the ordinary ML estimator suffers from high sampling variability. The restricted estimator imposes an a priori value on the standard deviation and freely estimates the mean, exploiting the known empirical stability of the former to obtain less variable estimates of the latter. Simulation results validate the conjecture that restricted ML behaves like restricted ordinary least squares (OLS), whose properties are well established on theoretical grounds. Both estimators display smaller sampling variability when constrained, whether the restrictions are correct or not. The bias induced by incorrect restrictions sets up a decision problem involving a bias-precision tradeoff, which can be evaluated using the mean squared error (MSE) criterion. Simulated MSEs suggest that restricted ML estimation offers important advantages when samples are small and truncation points are high, so long as the true standard deviation is within roughly 0.5 cm of the chosen value.     

Orientation and rotational freedom of fluorescent probes in lecithin bilayers

Summary The fluorescence polarization properties of lecithin bilayers stained with 2,6-MANS and 1,8-ANS under applied potential steps have been studied. The fluorescence signal components of both dyes were found to have different sign and relative amplitude, suggesting that 1,8-ANS and 2,6-MANS behave differently when bound to black lipid membranes. In order to determine the location and the extent of rotational brownian motions of the bound chromophores, the experimental data were analyzed by using a simplified physico-mathematical model. According to it 2,6-MANS appears to have a ratio /gt higher than 1,8-ANS ( being the rotational relaxation of in plane rotations and the lifetime of the excited singlet state of the bound molecules), suggesting that the former chromophore is more tightly held inside the bilayers. Furthermore, 2,6-MANS is found to possess the absorption and emission oscillators more closely oriented to the normal of membrane surface, while 1,8-ANS has both oscillators almost near the plane of the bilayers. The results furnish also a fair estimate of the random molecular motion own by the phospholipid molecules at room temperature. The comparison of the present data with those obtained from squid axon membranes confirms the validity of the proposed physical model, yielding a rough estimate of the axon membrane-area covered by integral protein macromolecules. These preliminary results derived from lecithin model membranes suggest that fluorescence polarization techniques can provide valuable informations if applied to study the macromolecular organization of in vitro reconstituted membranes.Abbreviations 2,6-MANS 2-n-methylanilinonaphthalene-6-sulfonate - 1,8-ANS 1-anilinonaphthalene-8-sulfonate     

Effects of data imbalance on estimation of heritability

Summary Effects of data imbalance on bias, sampling variance and mean square error of heritability estimated with variance components were examined using a random two-way nested classification. Four designs, ranging from zero imbalance (balanced data) to low, medium and high imbalance, were considered for each of four combinations of heritability (h²=0.2 and 0.4) and sample size (N=120 and 600). Observations were simulated for each design by drawing independent pseudo-random deviates from normal distributions with zero means, and variances determined by heritability. There were 100 replicates of each simulation; the same design matrix was used in all replications. Variance components were estimated by analysis of variance (Henderson's Method 1) and by maximum likelihood (ML). For the design and model used in this study, bias in heritability based on Method 1 and ML estimates of variance components was negligible. Effect of imbalance on variance of heritability was smaller for ML than for Method 1 estimation, and was smaller for heritability based on estimates of sire-plus-dam variance components than for heritability based on estimates of sire or dam variance components. Mean square error for heritability based on estimates of sire-plus-dam variance components appears to be less sensitive to data imbalance than heritability based on estimates of sire or dam variance components, especially when using Method 1 estimation. Estimation of heritability from sire-plus-dam components was insensitive to differences in data imbalance, especially for the larger sample size.Supported by grants from the Illinois Agricultural Experiment Station and the University of Illinois Research Board. Charles Smith, H. W. Norton and D. Gianola contributed valuable suggestions     

Hydrodynamic characteristics of two-phase inverse fluidized bed

Hydrodynamic characteristics of a new mode of liquid-solid fluidization, termed as inverse fluidization in which low density floating particles are fluidized with downward flow of liquid, are experimentally investigated. The experiments are carried out with low density particles (<534 kg/m³) which allow high liquid throughputs in the system. During the operation, three regimes, namely, packed, semi-fluidization and fully fluidization are encountered. Empirical correlations are proposed to predict the pressure drop in each regime. A computational procedure is developed to simulate the variation of pressure drop with liquid velocity.List of Symbols Ar modified Archimedes number, d _p ³ (– _s)g/² - d _p particle diameter, mm - f friction factor (eq. 2) - g acceleration due to gravity, m/s² - H total bed height, m - H _c height of the column, m - H_f height of fluidized bed, m - H₀ height of initial bed, m - H_p height of the packed bed, m - (p) pressure drop across the bed, N/m² - (p) _f pressure drop across fluidized bed section, N/m² - (p) _p pressure drop across the packed bed section, N/m² - (p) _sf total pressure drop in semifluidization regime, N/m² - Re Reynolds number, d _pU ₁/ - Re_m modified Reynolds number, d _pU ₁/(1– _p) - U ₁ superficial liquid velocity, m/s - U_mf minimum fluidization velocity, m/s - U_osf onset fluidization velocity, m/s Greek Letters _f voidage of fluidized bed - _p voidage of packed bed - liquid viscosity, kg/ms - liquid density, kg/m³ - _s particle density, kg/m³     

Variance-component estimation from human sibship data

The large-sample relative efficiencies of the analysis-of-variance (ANOVA) estimators of variance components and the intraclass correlation coefficient rho are investigated for the unbalanced single classification in the context of family studies. The efficiency of an analysis based on the method of unweighted group means is also investigated. From a Monte Carlo study which generates the group sizes from typical family-size distributions it is found that the relative efficiency of the ANOVA estimators of the between-group variance component exceeds 95% for values of .2 less than or equal to rho less than or equal to .4, but can fall below 60% for values of rho that are very close to zero. For the estimation of the between-group variance component the method of unweighted means tends to be preferable to the ANOVA method only if rho greater than .5.     

On the Estimation of Heritability from Unbalanced Data

The distribution and moments, of ANOVA estimator of heritability are given under unbalanced random model. These expressions are used to investigate the effect of unbalancedness on the bias and variance/MSE of the estimator and also the validity of certain approximations for its variance, numerically. The computed results reveal that the unbalancedness increases both the bias and variance/MSE of the estimator and the Smith-approximation for the variance of the estimator provides better accuracy.