Adaptive choice of trimming proportions

We consider Jaeckel's (1971,Ann. Math. Statist.,42, 1540–1552) proposal for choosing the trimming proportion of the trimmed mean in the more general context of choosing a trimming proportion for a trimmedL-estimator of location. We obtain higher order expansions which enable us to evaluate the effect of the estimated trimming proportion on the adaptive estimator. We find thatL-estimators with smooth weight functions are to be preferred to those with discontinuous weight functions (such as the trimmed mean) because the effect of the estimated trimming proportion on the estimator is of ordern ^–1 rather thann ^–3/4. In particular, we find that valid inferences can be based on a particular smooth trimmed mean with its asymptotic standard error and the Studentt distribution with degrees of freedom given by the Tukey and McLaughlin (1963,Sankhy Ser. A,25, 331–352) proposal.     

An old-new tool for nuclear analysis: Time-of-Flight spectrometry

The Time-of-Flight (ToF) technique can be used for mass identification, for separation of a specified mass or for measuring the energy of a given mass particle. The instrumentation required is simple and low in cost. The method features high yield, transmission efficiency is typically of 5 to 20%. Even with short flight paths (5 to 10 cm), ToF has adequate mass resolution (M/M300 to 500) for identifying isotopic species. This paper examines the scope of ToF in nuclear science with examples in mass spectrometry, in mass separation and in kinetic energy measurements of fixed mass particles. An example of the latter is the energy determination of recoil nuclei. If a recoil is produced inside a solid, the residual recoil energy reveals the depth from which it originates. This approach is used for profiling nitrogen via¹⁴N(n, p)¹⁴C. The ToF measurement of the¹⁴C recoil energies reveals the depth distribution of nitrogen with better than 50 Å resolution.     

Studies in neutron depth profiling

This paper describes first the application of neutron depth profiling (NDP) for measuring the distribution of⁶Li in LiAlO₂ ceramics. Using a surface barrier detector for detecting³H produced in⁶Li(n, )³H,⁶Li was profiled to a depth of 14 m in the ceramics. Secondly, a new methodology is presented for NDP with enhanced capabilities based on measuring the energy of recoiling nuclei from (n, p) and (n, ) reactions by time-of-flight mass spectrometry. The scope of recoil nucleus time-of-flight mass spectrometry (RN-TOF-MS) includes profiling of¹⁰B,¹⁴N,¹⁷O,³³S,³⁵Cl,⁴⁰K. Probe depths may be of a few tens nanometers. RN-TOF-MS complements and refines NDP based on charged particle (p or ) spectrometry.     

Analytical implications of zeolites in overlayers at electrodes

A review is given of past and potential analytical and other applications of electrodes overlayered with zeolites.     

Molecular modeling studies of novel heteroarotinoids

The molecular structure and conformational properties of structurally related oxo and thio heteroarotinoids have been calculated by employing AM1 molecular orbital and both MM2P and Chem-X “optimize” molecular mechanics methods, and the results have been compared with crystal structure data. For the cis and trans oxo heteroarotinoids, MM2P gives values of the bridge torsion angles ?₁ and ?₂ in closest agreement with the crystal structure, and all three computational methods yield values of ?₁ and ?₂ within about 10° of that found in the crystal structures. All three computational methods locate a minimum-energy conformation for the trans isomer corresponding to the two bridged aryl rings being mutually perpendicular, in agreement with the crystal structure and similar to that found for the structurally analogous trans-stilbene. The calculated heteroring geometries also reproduce the twist-sofa conformation observed for the crystal structure. Calculated conformational energies versus ?₁ and ?₂ indicate broad energy wells about the minimum-energy conformation with barriers to rotation at the planar and perpendicular conformations, and with higher barriers found for the more sterically congested cis isomer. The corresponding cis and trans thio heteroarotinoids exhibit conformational properties similar to their oxo analogues. Both AM1 and MM2P fare poorly in reproducing the crystal structure values of the sulfur-containing bond lengths and bond angles. The C-S bonds found in these thio heteroarotinoids may possess more double-bond character than accounted for in the calculations. Also, the results suggest that the MM2P sulfur-related force-field parameters adopted for these calculations may require further refinement.     

A trial phase function method for a class of λ-ω reaction-diffusion systems: Reduction to a Schrödinger type problem in an eigen sub-domain

The perturbed central force problem $\text{γ}{}_{\mathrm{xx}}\text{? ?}{}^2\text{γ}\text{a}\text{?}{}^2\text{+ γλ(γ) = 0, γ}\text{a}\text{?}{}_{\mathrm{x}}\text{+ 2}\text{a}\text{?}\text{γ}{}_{\mathrm{x}}\text{+ γ[}\text{}\text{?}\text{gw(γ}{}^1\text{) ?}\text{}\text{?}\text{gw(γ)] = 0}$ arising from the λ-ω system

$\text{α}\text{αt}\text{C}{}_1\text{C}{}_2\text{=}\text{λ}\text{?ω}\text{ω}\text{λ}\text{C}{}_1\text{C}{}_2\text{+}\text{α}\text{αt}\text{C}{}_1\text{C}{}_2$

where $\text{c}{}_1\text{=}\text{γ}\text{(x)cosθ(x,t), c}{}_2\text{=}\text{γ}\text{(x)sinθ(x,t), θ = σt ? ?∝}{}^{\mathrm{x}}\text{a}\text{?}\text{(x′)dx′}\text{and}\text{ω = ?}\text{}\text{?}\text{gw(}\text{γ}\text{)}$ is considered for the class $\text{λ}\text{=}\text{}\text{?}\text{gw}\text{= 1 ? g(}\text{γ}\text{)}$. The resulting linear equation in $\text{γ(x), γ}{}_{\mathrm{xx}}\text{+ 2}\text{a}\text{?}\text{γ}{}_{\mathrm{x}}\text{+}\text{γ[α}{}^2\text{+}\text{a}\text{?}{}_{\mathrm{x}}\text{?}\text{?}{}^2\text{a}\text{?}{}^2\text{] = 0}$ is solved with the aid of a class of trial phase functions $\text{a}\text{?}{}_{\mathrm{T}}\text{(x)}$ generated by the unperturbed central force problem for the case g(γ) = γ². An application of the Liouville-Green approximation procedure reduces the system to a Schrödinger type boundary value problem in an eigen sub-domain. The analytical estimates for α are in reasonable agreement with the results of numerical integration of the nonlinear system. The eigenfunctions γ(x) display expected oscillatory behaviour inside an eigen sub-domain. The higher modes and the span of the most extended centre structure are estimated and interpreted in the context of WKBJ connection formula.     

Rational inhibitor design and iterative screening in the identification of selective plasmodial cyclin dependent kinase inhibitors

New chemical classes of compounds must be introduced into the malaria drug development pipeline in an effort to develop new chemotherapy options for the fight against malaria. In this review we describe an iterative approach designed to identify potent inhibitors of a kinase family that collectively functions as key regulators of the cell cycle. Cyclin-dependent protein kinases (CDKs) are attractive drug targets in numerous diseases and, most recently, they have become the focus of rational drug design programs for the development of new antimalarial agents. Our approach uses experimental and virtual screening methodologies to identify and refine chemical inhibitors and increase the success rate of discovering potent and selective inhibitors. The active pockets of the plasmodial CDKs are unique in terms of size, shape and amino acid composition compared with those of the mammalian orthologues. These differences exemplified through the use of screening assays, molecular modeling, and crystallography can be exploited for inhibitor design. To date, several classes of compounds including quinolines and oxindoles have been identified as selective inhibitors of the plasmodial CDK7 homologue, Pfmrk. From these initial studies and through the iterative rational drug design process, more potent, selective, and most importantly, chemically unique compound classes have been identified as effective inhibitors of the plasmodial CDKs and the malarial parasite.     

Preparation of peptide p-nitroanilides using an aryl hydrazine resin

[reaction: see text] Peptide p-nitroanilides are useful compounds for studying protease activity; however, the poor nucleophilicity of p-nitroaniline makes their preparation difficult. We describe a new efficient approach for the Fmoc-based synthesis of peptide p-nitroanilides using an aryl hydrazine resin. Mild oxidation of the peptide hydrazide resin yields a highly reactive acyl diazene that efficiently reacts with weak nucleophiles. We have prepared several peptide p-nitroanilides, including substrates for the Lethal Factor protease from B. anthracis.