On the de la Garza Phenomenon

DOI: 10.1214/09-AOS787Deriving optimal designs for nonlinear models is, in general, challenging. One crucial step is to determine the number of support points needed. Current tools handle this on a case-by-case basis. Each combination of model, optimality criterion and objective requires its own proof. The celebrated de la Garza Phenomenon states that under a (p − 1)th-degree polynomial regression model, any optimal design can be based on at most p design points, the minimum number of support points such that all parameters are estimable. Does this conclusion also hold for nonlinear models? If the answer is yes, it would be relatively easy to derive any optimal design, analytically or numerically. In this paper, a novel approach is developed to address this question. Using this new approach, it can be easily shown that the de la Garza phenomenon exists for many commonly studied nonlinear models, such as the Emax model, exponential model, three- and four-parameter log-linear models, Emax-PK1 model, as well as many classical polynomial regression models. The proposed approach unifies and extends many well-known results in the optimal design literature. It has four advantages over current tools: (i) it can be applied to many forms of nonlinear models; to continuous or discrete data; to data with homogeneous or nonhomogeneous errors; (ii) it can be applied to any design region; (iii) it can be applied to multiple-stage optimal design and (iv) it can be easily implemented.Supported by NSF Grants DMS-07-07013 and DMS-07-48409. AMS 2000 subject classifications. Primary 62K05; secondary 62J12

Universal Optimality in Balanced Uniform Crossover Design

Kunert [Ann. Statist. 12 (1984) 1006-1017] proved that, in the class of repeated measurement designs based on t treatments, p = t periods and n = λt experimental units, a balanced uniform design is universally optimal for direct treatment effects if t ≥ 3 and λ = 1, or if t ≥ 6 and λ = 2. This result is generalized to t ≥ 3 as long as λ ≤ (t −1)/2.Primarily sponsored by NSF Grant DMS-01-03727, National Cancer Institute Grant P01-CA48112-08 and NIH Grant P50-AT00155 ( jointly supported by the National Center for Complementary and Alternative Medicine, the Office of Dietary Supplements, the Office for Research on Women's Health, and the National Institute of General Medicine). The contents are solely the responsibility of the authors and do not necessarily represent the official views of NIH

Dark Matter and Dark Energy

I briefly review our current understanding of dark matter and dark energy. The first part of this paper focusses on issues pertaining to dark matter including observational evidence for its existence, current constraints and the `abundance of substructure' and `cuspy core' issues which arise in CDM. I also briefly describe MOND. The second part of this review focusses on dark energy. In this part I discuss the significance of the cosmological constant problem which leads to a predicted value of the cosmological constant which is almost $10^{123}$ times larger than the observed value \la/8\pi G \simeq 10^{-47}GeV$^4$. Setting \la to this small value ensures that the acceleration of the universe is a fairly recent phenomenon giving rise to the `cosmic coincidence' conundrum according to which we live during a special epoch when the density in matter and \la are almost equal. Anthropic arguments are briefly discussed but more emphasis is placed upon dynamical dark energy models in which the equation of state is time dependent. These include Quintessence, Braneworld models, Chaplygin gas and Phantom energy. Model independent methods to determine the cosmic equation of state and the Statefinder diagnostic are also discussed. The Statefinder has the attractive property \atridot/a H^3 = 1 for LCDM, which is helpful for differentiating between LCDM and rival dark energy models. The review ends with a brief discussion of the fate of the universe in dark energy models.Comment: 40 pages, 11 figures, Lectures presented at the Second Aegean Summer School on the Early Universe, Syros, Greece, September 2003, New References added Final version to appear in the Proceeding

Rapid and decisive determination of Cr6+ using electrospray ionization mass spectrometry

Cr6+ complexed with diethyldithiocarbamate (DDC) was extracted into 0.1 volume of octanol in the presence of citric acid. The extracted compound was determined to be CrOH(DDC)3 + by electrospray ionization mass spectrometry. The peak at m/z 513 derived from 52Cr was so high that only 5 pg of Cr6+ could be determined in 10 min

Strong Consistency of MLE in Nonlinear Mixed-effects Models with Large Cluster Size

The search for conditions for the consistency of maximum likelihood estimators in nonlinear mixed effects models is difficult due to the fact that, in general, the likelihood can only be expressed as an integral over the random effects. For repeated measurements or clustered data, we focus on asymptotic theory for the maximum likelihood estimator for the case where the cluster sizes go to infinity, which is a minimum assumption required to validate most of the available methods of inference in nonlinear mixed-effects models. In particular, we establish sufficient conditions for the (strong) consistency of the maximum likelihood estimator of the fixed effects. Our results extend the results of Jennrich (1969) and Wu (1981) for nonlinear fixed-effects models to nonlinear mixed-effects models

Accurate spectroscopy of Sr atoms

We report the frequency measurement with an accuracy in the 100 kHz range of several optical transitions of atomic Sr : $^1S_0- ^3P_1$ at 689 nm, $^3P_1- ^3S_1$ at 688 nm and $^3P_0- ^3S_1$ at 679 nm. Measurements are performed with a frequency chain based on a femtosecond laser referenced to primary frequency standards. They allowed the indirect determination with a 70 kHz uncertainty of the frequency of the doubly forbidden 5s^2^1S_0- 5s5p^3P_0 transition of $^{87}$Sr at 698 nm and in a second step its direct observation. Frequency measurements are performed for $^{88}$Sr and $^{87}$Sr, allowing the determination of $^3P_0$, $^3P_1$ and $^3S_1$ isotope shifts, as well as the $^3S_1$ hyperfine constants.Comment: 12 pages, 16 figure

DNA Renaturation at the Water-Phenol Interface

We study DNA adsorption and renaturation in a water-phenol two-phase system, with or without shaking. In very dilute solutions, single-stranded DNA is adsorbed at the interface in a salt-dependent manner. At high salt concentrations the adsorption is irreversible. The adsorption of the single-stranded DNA is specific to phenol and relies on stacking and hydrogen bonding. We establish the interfacial nature of a DNA renaturation at a high salt concentration. In the absence of shaking, this reaction involves an efficient surface diffusion of the single-stranded DNA chains. In the presence of a vigorous shaking, the bimolecular rate of the reaction exceeds the Smoluchowski limit for a three-dimensional diffusion-controlled reaction. DNA renaturation in these conditions is known as the Phenol Emulsion Reassociation Technique or PERT. Our results establish the interfacial nature of PERT. A comparison of this interfacial reaction with other approaches shows that PERT is the most efficient technique and reveals similarities between PERT and the renaturation performed by single-stranded nucleic acid binding proteins. Our results lead to a better understanding of the partitioning of nucleic acids in two-phase systems, and should help design improved extraction procedures for damaged nucleic acids. We present arguments in favor of a role of phenol and water-phenol interface in prebiotic chemistry. The most efficient renaturation reactions (in the presence of condensing agents or with PERT) occur in heterogeneous systems. This reveals the limitations of homogeneous approaches to the biochemistry of nucleic acids. We propose a heterogeneous approach to overcome the limitations of the homogeneous viewpoint