Design Efficiency and Estimation for Component Amount Models

Component amount models were introduced by Piepel and Cornell (1985) to describe mixture experiments where the response depends not only on the proportions of the components but also on the total amount. The extended simplex centroid design supported by the barycenters corresponding to the regression functions in the model is D-optimal or fails to be D-optimal depending on the regression model under consideration. For two special component amount models, namely the ν-tic polynomial and the minimum polynomial of degree ν, the efficiency of the simplex centroid design was investigated. This covers the presentation of new results concerning the D-optimality as well as the assessment of the simplex centroid design in non-optimal situations by means of the G-efficiency. Formulae for the least squares estimates as well as their variances are presented.     

Optimal Split-plot Designs for a Mixed Model

Exact tests are given, for the usual hypotheses on split-plot models with random blocks and fixed treatment effects, considering different numbers of blocks for each level of whole-plot treatment and assuming normally distributed observations. U- and D-optimal designs are considered with respect to the tests of main effects and interactions as well as to estimation of parameters.     

Optimal design for the dose-response screening of tight-binding enzyme inhibitors

Optimal experimental designs for the dose–response screening of enzyme inhibitors were studied within the framework of the Box–Lucas theory. If the enzyme concentration E is considered as a fixed constant, an exact two-point D-optimal design consists of a pair of inhibitor concentrations equal to I₁=0 and I₂=E+K, where K is the apparent inhibition constant. If the enzyme concentration is treated as an adjustable parameter, an empirical three-point D-optimal design consists of three inhibitor concentrations equal to I₁=0, I₂=E+3K, and I₃=0.7E. These results were applied to design optimized, irregularly spaced concentration series for routine inhibitor screening. A heuristic Monte Carlo simulation study confirmed that the optimized dilution series is significantly more efficient than the classic series characterized by a constant dilution ratio. An online calculator to create optimized dilution series is freely available at http://www.biokin.com/design/.     

Optimality of Some Class of Incomplete Block Designs

A class of incomplete block designs called C-design, was considered by Caliński (1971), Saha (1976), Ceranka (1983) and Ceranka , Kozłowska (1983, 1984). In this paper we extend the theory of block designs having the C-property. We consider optimality of C-designs with respect to any criterion of a described form. Das and Kageyama (1991) considered a class of E-optimal proper efficiency balanced designs (strictly speaking, Das and Kageyama considered E_R-optimality of some class of block designs). Hence we consider E_R, A_R, D_R optimality of C-designs.     

Sequential Designs for Genetic Epidemiological Linkage or Association Studies A Review of the Literature

Objectives. The cost of a genetic linkage or association study is largely determined by the number of individuals to be recruited, phenotyped, and genotyped. The efficiency can be increased by using a sequential procedure that reduces time and cost on average. Two strategies for sequential designs in genetic epidemiological studies can be distinguished: One approach is to increase the sample size sequentially and to conduct multiple significance tests on accumulating data. If significance or futility can be assumed with a certain probability, the study is stopped. Otherwise, it is carried on to the next stage. The second approach is to conduct early linkage analyses on a coarse marker grid, and to increase marker density in later stages. Interim analyses are performed to select interesting genomic areas for follow up. The aim of this article is to give a review on sequential procedures in the context of genetic linkage and association studies. Methods. A systematic literature search was performed in the Medline and the Linkage Bibliography databases. Articles were defined as relevant if a sequential design was proposed or applied in genetic linkage or association studies. Results. The majority of proposed study designs is developed to meet the demands of specific studies and lacks a theoretical foundation. A second group of procedures is based on simulation results and principally restricted to the specific simulated situations. Finally, some theoretically founded procedures have been proposed that are discussed in detail. Conclusions. Although interesting and promising procedures have been suggested, they still lack realizations for practical purposes. In addition, further developments are required to adapt sequential strategies for optimal use in genetic epidemiological studies.     

Optimal nested row-column designs with specified components

We consider nested row-column designs where each of the rowand column component designs is specified. For the case thateach of the component designs has second-order balance, we definesuch a nested row-column design to be special if it is generallybalanced, with the smallest possible number of canonical treatmentcontrasts having the lower canonical efficiency factor in bothcomponents. We show that if any special row-column design existsthen it is A-optimal over all nested row-column designs withthe given components.     

Conditional Point Estimation in Adaptive Group Sequential Test Designs

It is well known that point estimates in group sequential designs are biased. This also applies to adaptive designs that enable, e.g., data driven reassessments of group sample sizes. For triangular designs, Whitehead (1986) (Biometrika 73 , 573–581) proposed a bias adjusted estimate. But this estimate is not feasible in adaptive designs although it is in group sequential designs. Furthermore, there is a waste of information because it does not use the information at which stage the trial was stopped. We present a modification which does use this information and which is applicable to adaptive designs. The modified estimate achieves an improvement in group sequential designs and shows similar results in adaptive designs.     

Construction and Analysis of an Augmented Lattice Square Design

Augmented designs are useful for screening experiments involving large numbers of new and untried treatments. Since resolvable row‐column designs are useful for controlling extraneous variation, it is desirable to use such designs for the check or standard treatments to construct augmented lattice square experiment designs. A simple procedure is described for constructing such designs using c = 2k and c = 3k check treatments and n = rk(k ‐— 2) and n = rk(k — 3) new treatments, respectively, r being the number of complete blocks. A trend analysis for these designs, which allows for solutions of fixed effects, is presented. The random effects case is also discussed. A SAS computer code and the output from this code illustrated with a small numerical example are available from the author.     

Pre- and Postnatal Ontogeny and Characterization of Dopaminergic D2, Serotonergic S2, and Spirodecanone Binding Sites in Rat Forebrain

Abstract: The ontogeny of binding sites for [³H] spiperone was studied in time-pregnant rats. Binding of [³H]spiperone to fresh homogenates of pre- and postnatal rat forebrain was characterized by Scatchard analysis and competition experiments with a number of dopaminergic and serotonergic agonists and antagonists and additional substances. A convenient discrimination of three high-affinity sites, i.e., the dopaminergic D₂, serotonergic S₂, and spirodecanone (Sd) sites, was obtained with l-(–)sulpiride and cis-flupenthixol. The analgesic R5573 was found not to be specific for the Sd site but to interact with all three sites. The three binding sites became detectable in sequential order. S₂ and D₂ binding sites were first found at embryonic days 15.75 and 17.75, respectively. The Sd site did not appear before postnatal day 8. All three binding sites reached adult values at approximately postnatal day 30. During the prenatal period, the increase in the number of D₂ binding sites paralleled the rise in forebrain dopamine concentrations. The kinetics of D₂ and S₂ sites were the same at embryonic day 19.75 and postnatal day 30. These observations provide evidence for the presence of the receptor substrate for actions of neuroleptics on dopaminergic and serotonergic systems during fetal life.     

Data and knowledge based experimental design for fermentation process optimization

A novel method for the sequential experimental design in order to optimize fed-batch fermentations was applied to a hyaluronidase fermentation by Streptococcus agalactiae. A Λ-optimal design was introduced to minimize the model parameter estimation error and to maximize the performance of the fermentation process. The method employs hybrid models that contain mechanistic, fuzzy and neural network components.     

Evaluation of sequential sampling plans for estimation of leafmines density of Liriomyza sativae Blanchard (Diptera: Agromyzidae) in cucumber greenhouses

This study was conducted to develop sequential sampling plans to estimate leafmine density by Liriomyza sativae (Blanchard) at two fixed-precision levels in a cucumber greenhouse. The within-greenhouse spatial patterns of leafmines were aggregated. The slopes and intercepts of Taylor’s power law did not differ between years. A fixed-precision level sampling plan was developed using the parameters of Taylor’s power law generated from total number of leafmines in a cucumber leaf at two precision levels (D) of 0.1 and 0.25. The resulting sampling plans were tested with sequential bootstrap simulations (n = 500) using 10 independent data sets for validation. Bootstrap simulation within a wide range of densities demonstrated that actual D′ values at desired D = 0.25 averaged less than or equal to 0.25 in all cases. Even at the lowest density of leafmine (0.27 mine per leaf), the actual mean D′ was 0.24 at D = 0.25. This result shows that the sampling plan developed in this study is effective and reliable for estimating the mine densities in cucumber greenhouses.     

Optimal adaptive randomized designs for clinical trials

Optimal decision-analytic designs are deterministic. Such designsare appropriately criticized in the context of clinical trialsbecause they are subject to assignment bias. On the other hand,balanced randomized designs may assign an excessive number ofpatients to a treatment arm that is performing relatively poorly.We propose a compromise between these two extremes, one thatachieves some of the good characteristics of both. We introducea constrained optimal adaptive design for a fully sequentialrandomized clinical trial with k arms and n patients. An r-designis one for which, at each allocation, each arm has probabilityat least r of being chosen, 0 r 1/k. An optimal design amongall r-designs is called r-optimal. An r₁-design is also an r₂-designif r₁ r₂. A design without constraint is the special case r = 0and a balanced randomized design is the special case r = 1/k.The optimization criterion is to maximize the expected overallutility in a Bayesian decision-analytic approach, where utilityis the sum over the utilities for individual patients over a‘patient horizon’ N. We prove analytically thatthere exists an r-optimal design such that each patient is assignedto a particular one of the arms with probability 1 – (k – 1)r,and to the remaining arms with probability r. We also show thatthe balanced design is asymptotically r-optimal for any givenr, 0 r < 1/k, as N/n  . This implies that everyr-optimal design is asymptotically optimal without constraint.Numerical computations using backward induction for k = 2arms show that, in general, this asymptotic optimality featurefor r-optimal designs can be accomplished with moderate trialsize n if the patient horizon N is large relative to n. We alsoshow that, in a trial with an r-optimal design, r < 1/2,fewer patients are assigned to an inferior arm than when followinga balanced design, even for r-optimal designs having the samestatistical power as a balanced design. We discuss extensionsto various clinical trial settings.     

Efficient analysis of protein 2D NMR spectra using the software packageEASY

Summary The programEASY supports the spectral analysis of biomacromolecular two-dimensional (2D) nuclear magnetic resonance (NMR) data. It provides a user-friendly, window-based environment in which to view spectra for interactive interpretation. In addition, it includes a number of automated routines for peakpicking, spin-system identification, sequential resonance assignment in polypeptide chains, and cross peak integration. In this uniform environment, all resulting parameter lists can be recorded on disk, so that the paper plots and handwritten notes which normally accompany manual assignment of spectra can be largely eliminated. For example, in a protein structure determination by 2D¹H NMR,EASY accepts the frequency domain datasets as input, and after combined use of the automated and interactive routines it can yield a listing of conformational constraints in the format required as input for the calculation of the 3D structure. The program was extensively tested with current protein structure determinations in our laboratory. In this paper, its main features are illustrated with data on the protein basic pancreatic trypsin inhibitor.     

Comparison of pheromone trap design and lures for Spodoptera frugiperda in Togo and genetic characterization of moths caught

Fall armyworm, Spodoptera frugiperda (JE Smith) (Lepidoptera: Noctuidae), is a pest of grain and vegetable crops endemic to the Western Hemisphere that has recently become widespread in sub‐Saharan Africa and has appeared in India. An important tool for monitoring S. frugiperda in the USA is pheromone trapping, which would be of value for use with African populations. Field experiments were conducted in Togo (West Africa) to compare capture of male fall armyworm using three commercially available pheromone lures and three trap designs. The objectives were to identify optimum trap × lure combinations with respect to sensitivity, specificity, and cost. Almost 400 moths were captured during the experiment. Differences were found in the number of S. frugiperda moths captured in the various trap designs and with the three pheromone lures, and in the number of non‐target moths captured with each lure. The merits of each trap × lure combination are discussed with respect to use in Africa. A nearly equal number of COI‐CS (161) and COI‐RS (158) moths was captured with no differences found in COI marker proportions among traps or lures. However, the diagnostic rice strain marker Tpi was rarely found. Overall, the genetic characterization of the pheromone trap collections indicated a consistent distribution of genetic markers from 2016 to 2017, suggesting a population at or near equilibrium.     

Non-destructive measurement of dormant bud respiration rates

The lack of an indicator of the state of bud development during the dormant period has been a major difficulty in studying the effects of winter chilling on subsequent shoot growth and flowering. We considered that respiration rate (R _D ) might provide such an index, so developed a technique for the non-destructive measurement of the R _D of individual dormant buds of kiwifruit (Actinidia deliciosa). A closed configuration gas exchange system was used. The low R _D of dormant buds required the use of an unusually small system volume. As a consequence, it was necessary to modify the conventional closed system so that most of the system volume could be sampled for analysis. Increases in CO₂ concentration during a measurement were determined by injecting gas samples into a stream of air flowing through an infrared gas analyser. The technique was found to be reliable even at R _D as low as 20 pmol s-1. Error analysis showed that under normal operating conditions the coefficient of variation was approximately 3 %. With two operators, measurements could be made at the rate of one bud every four minutes. The ability to make non-destructive measurements has the advantage of enabling us to make sequential measurements on individual buds and monitor subsequent development. The system could be readily adapted to other woody fruit species, providing that gas-tight seals can be established on individual buds. Use of the system is illustrated by measuring the temperature response of the R _D of dormant buds grown under contrasting conditions. All buds showed increasing R _D with increasing temperature in the range 15 to 25 °C. Buds which had grown in the coolest region, where bud break is usually the earliest, had the highest R _D when measured during early spring. This revised version was published online in September 2006 with corrections to the Cover Date.     

Designs Suited for Varietal Trials with Multiple Basals

DAS (1960) gave a method of construction of confounded balanced asymmetrical factorial designs of the type v × 2² by using BIB designs. In the present paper a method has been given for construction of balanced asymmetrical factorial designs of the type (v–t) × 2² by using truncated balanced incomplete block designs obtainable by omitting t treatments. Likewise, partially balanced asymmetrical factorial designs can also be obtained by omitting any particular treatment alongwith its first or second associate treatments from the v treatments of a PBIB design. We can get a large number of new designs not available in literature through this technique. These designs are well suited for varietal trials with multiple basals.     

Application of Partially Balanced Block Designs to Factorial Experiments

In this paper we present partially balanced block designs with F_p and C_p association schemes. These designs play a great role in the experimental theory since they can be applied to factorial experiments. A particular stress is put on the formulation of association schemes _p and C_p, presentation of exemplary constructions of these designs and their analysis of variance. The presented considerations are abundantly illustrated with examples.     

The diffusion-solubility of oxygen in lipid bilayers

The product, D_oα, of the oxygen diffusion coefficient, D_o, and the oxygen solubility, α, is determined in phosphatidylcholine bilayers at temperatures above the lipid phase transitions from ESR spin-exchange measurements. The resulting values of D_oα are in good agreement with those obtained from fluorescence-quenching experiments. The use of fatty acid spin labels makes it possible to measure D_oα as a function of the coordinate perpendicular to the bilayer surface. The results indicate that D_oα is a strong function of this coordinate; it is greatest in the bilayer center and least near the bilayer head groups.     

Determination of molecular weight by neutron scattering

Theoretical and practical advantages of neutron scattering for the determination of molecular weights of particles in solution are discussed. The method presented does not use known particles for calibration and is applicable to a wide molecular weight range (10⁴–10⁹); it is not sensitive to assumptions about the partial specific volume of the particles, and the experiments are performed quite easily in standard spectrophotometer cells using 100–500 μg of material. The method is nondestructive and the sample can be recovered totally. The use of D₂O in solvents has particular advantages especially for multicomponent particles, for which the in situ molecular weight of each component can be determined separately.