Data-dependent k/sub n/-NN and kernel estimators consistent for arbitrary processes

Let X/sub 1/, X/sub 2/,... be an arbitrary random process taking values in a totally bounded subset of a separable metric space. Associated with X/sub i/ we observe Y/sub i/ drawn from an unknown conditional distribution F(y|X/sub i/=x) with continuous regression function m(x)=E[Y|X=x]. The problem of interest is to estimate Y/sub n/ based on X/sub n/ and the data {(X/sub i/, Y/sub i/)}/sub i=1//sup n-1/. We construct appropriate data-dependent nearest neighbor and kernel estimators and show, with a very elementary proof, that these are consistent for every process X/sub 1/, X/sub 2/,.     

Satellite-to-Satellite Range-Rate Measurement

The measurement of range rate between two low-orbiting spacecraft with a precision of better than 1 ?m/s provides a means for sensing global gravity variability. An analysis is given to show the conditions under which this precision can be realized, with emphasis on the requirements of NASA's Geopotential Research Mission. Experimental results obtained with a millimeter-wave demonstration system are presented along with a proposed design for a spaceborne instrument.     

The A326S mutant of Gialpha1 as an approximation of the receptor-bound state

Agonist-bound heptahelical receptors activate heterotrimeric G proteins by catalyzing exchange of GDP for GTP on their alpha subunits. In search of an approximation of the receptor-alpha subunit complex, we have considered the properties of A326S Gialpha1, a mutation discovered originally in Gsalpha (Iiri, T., Herzmark, P., Nakamoto, J. M., Van Dop, C., and Bourne, H. R. (1994) Nature 371, 164-168) that mimics the effect of receptor on nucleotide exchange. The mutation accelerates dissociation of GDP from the alphai1beta1gamma2 heterotrimer by 250-fold. Nevertheless, affinity of mutant Gialpha1 for GTPgammaS is high in the presence of Mg2+, and the mutation has no effect on the intrinsic GTPase activity of the alpha subunit. The mutation also uncouples two activities of betagamma: stabilization of the GDP-bound alpha subunit (which is retained) and retardation of GDP dissociation from the heterotrimer (which is lost). For wild-type and mutant Gialpha1, beta gamma prevents irreversible inactivation of the alpha subunit at 30 degreesC. However, the mutation accelerates irreversible inactivation of alpha at 37 degreesC despite the presence of beta gamma. Structurally, the mutation weakens affinity for GTPgammaS by steric crowding: a 2-fold increase in the number of close contacts between the protein and the purine ring of the nucleotide. By contrast, we observe no differences in structure at the GDP binding site between wild-type heterotrimers and those containing A326S Gialpha1. However, the GDP binding site is only partially occupied in crystals of G protein heterotrimers containing A326S Gialpha1. In contrast to original speculations about the structural correlates of receptor-catalyzed nucleotide exchange, rapid dissociation of GDP can be observed in the absence of substantial structural alteration of a Galpha subunit in the GDP-bound state.     

Cause and effect analysis by fuzzy relational equations and a genetic algorithm

This paper proposes using a genetic algorithm as a tool to solve the fault diagnosis problem. The fault diagnosis problem is based on a cause and effect analysis which is formally described by fuzzy relations. Fuzzy relations are formed on the basis of expert assessments. Application of expert fuzzy relations to restore and identify the causes through the observed effects requires the solution to a system of fuzzy relational equations. In this study this search for a solution amounts to solving a corresponding optimization problem. An optimization algorithm is based on the application of genetic operations of crossover, mutation and selection. The genetic algorithm suggested here represents an application in expert systems of fault diagnosis and quality control.     

Sensitivity Analysis for Scheduling Problems

This paper represents a first attempt at a systematic study of sensitivity analysis for scheduling problems. Because schedules contain both combinatorial and temporal structures, scheduling problems present unique issues for sensitivity analysis. Some of the issues that we discuss have not been considered before. Others, while studied before, have not been explored in the context of scheduling. The applicability of these issues is illustrated using well-known scheduling models. We provide fast methods to determine when a previously optimal schedule remains optimal. Other methods restore an optimal schedule after a parameter change. The value of studying the sensitivity of an optimal sequence instead of the sensitivity of an optimal schedule is demonstrated. We show that, for some problems, sensitivity analysis results depend on the positions of jobs with changed parameters. We identify scheduling problems where performing additional or different computations during optimization facilitates sensitivity analysis. To improve the robustness of an optimal schedule, selection among multiple optimal schedules is considered. We discuss which types of sensitivity analysis questions are intractable because the scheduling problem itself is intractable. We also study how heuristic error bounds vary when the data of a scheduling problem is continuously modified. Although we focus on scheduling problems, several of the issues we discuss and our classification scheme can be extended to other optimization problems.     

Synthesis and in vitro antimalarial activity of sulfone endoperoxides

A series of 4,8-dimethyl-4-phenylsulfonylmethyl-2,3-dioxabicyclo[3.3.1]+ ++nonanes, carrying a variety of substituents at position-8 (4) were prepared by a short and efficient method from R-(+)-limonene. Key reactions include thiol oxygen cooxidation, and alkylation and acylation of a sterically hindered tertiary alcohol compatible with the endoperoxy functionality. Some of compounds 4, which are structurally related to yingzhaosu A (2), were found to exhibit in vitro antimalarial activity comparable to that of artemisinin (1) and superior to that of arteflene (3).     

Strategies for Weather-Dependent Data Acquisition

A strategy for data acquisition from a very distant spacecraft is presented, when the system performance can be severely degraded by the earth's weather due to the high microwave frequency being used. Two cases are considered, one in which there is a certain minimum data rate to be maintained and one in which there is not. The goal is to maximize expected data return, where we assume that there are always new data, or a backlog of old data, that can be sent if conditions are favorable. When there is no minimum rate to be maintained, the optimum strategy is typically the greedy strategy, which always transmits at that single rate which maximizes the expected data returned. If there is a minimum data rate which we strive to maintain even in adverse conditions, the optimum strategy transmits simultaneously at the minimum or base data rate and typically at a bonus data rate. We use a coding system designed for the bandwidthconstrained degraded broadcast channel. The optimum version of this system can, under realistic assumptions, save on the order of 5 dB over the conservative strategy of just transmitting at a single lower data rate.     

Crossed two-beam coherent anti-stokes Raman spectroscopy in dispersive media

Coherent anti-Stokes Raman spectroscopy (CARS) is a nonlinear optical wave mixing process that is used in gas-phase systems to determine the energy distribution of the probed species (usually N2) and, through a fitting procedure, the temperature giving rise to it. CARS signal strengths are maximized when the phase matching condition is met. Because gases are generally non-dispersive, this phase matching condition can be found geometrically as a function of the crossing angles between the CARS beams and their wavelengths. In addition, perfect phase matching in non-dispersive media occurs automatically for collinear beams. To improve spatial resolution, however, intersecting the laser beams is desirable. Being a third-order process, phase matching for CARS in gases typically requires three input laser beams. This paper discusses and demonstrates the issues of phase matching for CARS when the medium is dispersive, and the ability for CARS phase matching to occur with only two crossed laser beams (one pump and one probe). This two-beam X-CARS in dispersive media can be used as an alignment tool for gas-phase CARS and may be relevant as a simpler diagnostic in high-pressure environments. The paper also discusses the effects of non-ideal phase matching in dispersive and non-dispersive media.     

Orally active, hydrolytically stable, semisynthetic, antimalarial trioxanes in the artemisinin family

In only three chemical operations, natural trioxane lactone artemisinin (1) was converted into a series of C-10 carbon-substituted 10-deoxoartemisinin compounds 4-9. The three steps involved lactone reduction, replacement of the anomeric lactol OH by F using diethylaminosulfur trifluoride, and finally boron trifluoride-promoted substitution of F by aryl, heteroaryl, and acetylide nucleophiles. All of these C-10 nonacetal, chemically robust, enantiomerically pure compounds 4-9 have high antimalarial potencies in vitro against Plasmodium falciparum malaria parasites, and furans 5a and 5b and pyrrole 7a are antimalarially potent also in vivo even when administered to rodents orally.